Mcq

Front 1

Chronic pancreatitis:

Abdominal pain radiated to back

If s. amylase is low it can be excluded

Guarding is characteristic

NSAIDs are not contra-indicted.…

Back 1

Guarding and abdominal pain that directly radiates to the back are characteristic of acute pancreatitis.

In chronic pancreatitis pain is either epigastric / left upper abdomen and can be band like.

Reduced with bending forward or sitting.

And both serum lipase and amylase can be normal with the chronic pancreatitis.

NSAIDS ARE CONTRAINDICATED DUE TO THE POSSIBILITY OF GASTRIC ULCERATION.

Front 2

Xerostomia:Antidepressant treatment Sjogren’s syndromeElderlySialdenitisBeta blockers treatment

Back 2

Front 3

What are the immediate effects of transection of spinal cord ar vertibal level T 12Exaggerated reflexesHypotoniaHypertonic bladderPlantar upgoingSensory loss- umbilical level

Back 3

All

Front 4

malignancies:

Malignant melanoma – lung metastasis

Endometrial CA – early menapuse is a risk factor

Cervical CA- menorrhagia is a early characteristic feature🚀

Oesophageal CA- appetite is good

Everted edge- basal cell CA

Back 4

Ok

Front 5

Acute left ventricular failure management:

IV Frusemide

Aminophyllin

Beta blocker

Invasive ventilation

40% oxygen via CPAP mask

Back 5

Ok

Front 6

HypercalcaemiaOf primary hyperparathyroidism readily responds to steroidsCan be due to familial hypocalciuria when presents with recurrent renal stonesBone pain is typical of primary hyperparathyroidismThey can present with peptic ulcersForced dieresis and hydration are key RX51.WOF type of arthritis is not seen in psoriatic arthritisSymmetrical small joint arthropathyJaccoud’s arthropathySacroilitisMonoarthritisDIP joint arthropathy52. WOF is not aarecognized factor for osteoporosisEarly menarcheSmokingLow dietary calcium intakeSedentary lifestyleSlender body habbitus53. Following are recognized extra articular manifestations of rheumatoid arthritis exceptCaplans syndromePyoderma gangrenosumPhotosensitive rashScleromalacia perforansPeripheral neuropathy54.Following are poor prognostic factors in RA exceptPersistent synovitisEarly erosive changesExtra articular findingsNegative anti-CCP antibodiesPositive rheumatoid factor55. Features of temporal arteritis includeHeadacheNormal ESRScalp tendernessFeverJaw claudication56.Recognized side effects of steroid use includeAtypical features of infectionsProximal myopathyChronic pancreatitisAvascula necrosis of boneBone marrow suppression57. recogniozed side effects of MTX includeCirrhosisBM suppressionMouth ulcersAcute interstitial pneumonitisMaculopathy58. An 80 yr old male presented with painful swelling of his left knee joint of 2 weeks duration. A knee joint effusion was detected on examination.waht is the most likely causePseudogout of the kneeTrauma to the kneeSeptic arthritis of the kneeRheumatoid arthritis of the kneeOsteoarthritis of the knee59. Following are red flag signs of backache in a 60 yr old femalePain when getting up from the seated positionPresence of fever and weight lossShooting pain down the right legAssociation with bladder symptomsWorse early morning60. WOF are beneficial in Rx in acute goutColchicineAllopurinolCorticosteroidsNSAIDs Febuxostat61. A coronary angiogram with a view to revascularization is indicated inAll post infarct ptsA positive exercise ECG at a high workload not on anti anginal medicationAll unstable angina ptsAcute anterior STEMI with CI to thrombolyticsCardiogenic shock due to post MI VSD62. Recognized causes of sinus bradycardia includeHypoglycaemiaCholestatic jaundiceMyocarditisDigitalis toxicityRaised ICP63. Drugs safe to use in AF with WPW syndrome include the followingDigoxinVerapamilAmiodaroneSotalolFlecainide64. Acuired prolonged QT interval is known to be caused byHypercalcaemiaHypomagnesaemiaHyperkalaemiaAstemazole Erythromycin65. T/F regarding thrombolytic therapy in acute MIThrombolysis within 12 hours reduces ventricular damage and mortality rateActs in synergy with aspirin 150-300mg chewedTissue type plasminogen activator achieves higher reperfusion rates than skIV heparin therapy is mandatory after sk therapyPrimary PCI achieves higher reperfusion rates than thrombolytics66. Drugs known to prolong survival in unstable angina includeNitratesBeta blockersACEILMWHClopidogrel67. Following are known to prolong survival in acute MIPrimaty angioplastyACEIAspirinBeta blockersStatin68.T/F regarding coronary artery disease preventionGoal LDL cholesterol level for secondary prevention is <130mg/dlGoal LDL level for primary CAD prevention in diabetics is <160mg/dlGoal BP for diabetics is 140/90Goal LDL for primary CAD prevention in a hypertensive and a smoker is<130mg/dlStatin therapy is beneficial immediate post MI irrespective of the cholesterol level69. Drugs used in the primary prevention of CAD includeAspirinStatinBeta blockersClopidogrelNitrates70. Drugs known to prolong survival in heart failure includeNitrates with hydralazineDigoxinACEIARBSIvabradine71. Treatments known to prolong survival in heart failure includeMetoprololEplerononeAICDCardiac resynchronization therapyCardiac transplant72. Recognized indications for warfarin therapy includeIntermittent AFMS with sinus rhythmAF with a TIAAF with HT and DMPrimary pulmonary hypertension73. T/F regarding LMWHFondaparinaux is superior in efficacy to enoxaparinA standard dose of fondaparinaux is given to all pts irrespective of their bosy weightDose adjustment is required in renal dysfunctionAnticoagulant effect can be reversed with protamineLevel of anticoagulation can be monitored with activated factor x levels[Xa]74.Regarding severe hypercalcaemiaSymptoms occur when serum calcium is >3mmol/lRarely can present as comaST segment depression responsive to Rx of hypercalcaemia may be seenCalcitonin is the first line RX in MxGlucocorticoids should be considered in pts with vitamin D dependent hypercalcaemia75. Ischaemic strokeCan be reliably diagnosed at the bedside by a neurologist Surgery may be indicated in some pts with ischaemic strokeEarly administration of aspirin minimizes the cerebral damage due to the incident strokeHeparin should be considered in pts with progressive symptomsDexamethasone is standard care for large infarcts with progressive symptoms76. TIATo diagnose according to the new criteria a brain scan is requiredTIA with transient weakness is more likely to lead a disabling stroke than a TIA causing amaurosis fugaxEarly investigation is the key to preventing a strokeCHAD score helps prognosticate TIAsIf a pt with TIA has 99% occlusioj of the corresponding ICA he should be heparinised77. CI for thrombolysis includeCurrent aspirin useBeing on warfarinA minor stroke 1 month beforeAge over 80yrsDemonstrable clot occluding the ICA78.Parkinson’s diseaseBradykinesia is a typical featureHas a better prognosis than MSAHearing impairment may preceed motor symptomsSense of smell is often affected in PDEarly memory impairment suggests alternative diagnosis79. MSAThose with early autonomic dysfunction have a worse prognosisDiagnosis is made clinicallyMRI is helpful in the evaluation Humming bird sign is seen in MRIAnal sphincter EMG may show denervation changes80.TremorParkinsonian tremor is the most disabling type of tremorAction tremor is typically seen in essential tremorIntention tremor is seen in cerebellar diseaseBetablockers are very effective in controlling intention tremorOrthostatic tremor responds to clonazepam81. SleepHypersomnolence is the most common sleep disorderMost of adult sleep is in REMNormal person has about 10 sleep cycles every night Dreaming occurs in REMSleep walking occurs in NREM82. Subacute combined degeneration of the spinal cord80% of pts with pernicious anaemia suffer from this neurological conditionMost pts have associated megaloblastic anaemiaIs excluded if the pt has a normal Hb levelClinical features are caued by demyelination of posterior columns and spinothalamic tractsSphincters may get involved in later stagesCopper deficiency could present with similar clinical findings

HypercalcaemiaOf primary hyperparathyroidism readily responds to steroidsCan be due to familial hypocalciuria when presents with recurrent renal stonesBone pain is typical of primary hyperparathyroidismThey can present with peptic ulcersForced dieresis and hydration are key RX51.WOF type of arthritis is not seen in psoriatic arthritisSymmetrical small joint arthropathyJaccoud’s arthropathySacroilitisMonoarthritisDIP joint arthropathy52. WOF is not aarecognized factor for osteoporosisEarly menarcheSmokingLow dietary calcium intakeSedentary lifestyleSlender body habbitus53. Following are recognized extra articular manifestations of rheumatoid arthritis exceptCaplans syndromePyoderma gangrenosumPhotosensitive rashScleromalacia perforansPeripheral neuropathy54.Following are poor prognostic factors in RA exceptPersistent synovitisEarly erosive changesExtra articular findingsNegative anti-CCP antibodiesPositive rheumatoid factor55. Features of temporal arteritis includeHeadacheNormal ESRScalp tendernessFeverJaw claudication56.Recognized side effects of steroid use includeAtypical features of infectionsProximal myopathyChronic pancreatitisAvascula necrosis of boneBone marrow suppression57. recogniozed side effects of MTX includeCirrhosisBM suppressionMouth ulcersAcute interstitial pneumonitisMaculopathy58. An 80 yr old male presented with painful swelling of his left knee joint of 2 weeks duration. A knee joint effusion was detected on examination.waht is the most likely causePseudogout of the kneeTrauma to the kneeSeptic arthritis of the kneeRheumatoid arthritis of the kneeOsteoarthritis of the knee59. Following are red flag signs of backache in a 60 yr old femalePain when getting up from the seated positionPresence of fever and weight lossShooting pain down the right legAssociation with bladder symptomsWorse early morning60. WOF are beneficial in Rx in acute goutColchicineAllopurinolCorticosteroidsNSAIDs Febuxostat61. A coronary angiogram with a view to revascularization is indicated inAll post infarct ptsA positive exercise ECG at a high workload not on anti anginal medicationAll unstable angina ptsAcute anterior STEMI with CI to thrombolyticsCardiogenic shock due to post MI VSD62. Recognized causes of sinus bradycardia includeHypoglycaemiaCholestatic jaundiceMyocarditisDigitalis toxicityRaised ICP63. Drugs safe to use in AF with WPW syndrome include the followingDigoxinVerapamilAmiodaroneSotalolFlecainide64. Acuired prolonged QT interval is known to be caused byHypercalcaemiaHypomagnesaemiaHyperkalaemiaAstemazole Erythromycin65. T/F regarding thrombolytic therapy in acute MIThrombolysis within 12 hours reduces ventricular damage and mortality rateActs in synergy with aspirin 150-300mg chewedTissue type plasminogen activator achieves higher reperfusion rates than skIV heparin therapy is mandatory after sk therapyPrimary PCI achieves higher reperfusion rates than thrombolytics66. Drugs known to prolong survival in unstable angina includeNitratesBeta blockersACEILMWHClopidogrel67. Following are known to prolong survival in acute MIPrimaty angioplastyACEIAspirinBeta blockersStatin68.T/F regarding coronary artery disease preventionGoal LDL cholesterol level for secondary prevention is <130mg/dlGoal LDL level for primary CAD prevention in diabetics is <160mg/dlGoal BP for diabetics is 140/90Goal LDL for primary CAD prevention in a hypertensive and a smoker is<130mg/dlStatin therapy is beneficial immediate post MI irrespective of the cholesterol level69. Drugs used in the primary prevention of CAD includeAspirinStatinBeta blockersClopidogrelNitrates70. Drugs known to prolong survival in heart failure includeNitrates with hydralazineDigoxinACEIARBSIvabradine71. Treatments known to prolong survival in heart failure includeMetoprololEplerononeAICDCardiac resynchronization therapyCardiac transplant72. Recognized indications for warfarin therapy includeIntermittent AFMS with sinus rhythmAF with a TIAAF with HT and DMPrimary pulmonary hypertension73. T/F regarding LMWHFondaparinaux is superior in efficacy to enoxaparinA standard dose of fondaparinaux is given to all pts irrespective of their bosy weightDose adjustment is required in renal dysfunctionAnticoagulant effect can be reversed with protamineLevel of anticoagulation can be monitored with activated factor x levels[Xa]74.Regarding severe hypercalcaemiaSymptoms occur when serum calcium is >3mmol/lRarely can present as comaST segment depression responsive to Rx of hypercalcaemia may be seenCalcitonin is the first line RX in MxGlucocorticoids should be considered in pts with vitamin D dependent hypercalcaemia75. Ischaemic strokeCan be reliably diagnosed at the bedside by a neurologist Surgery may be indicated in some pts with ischaemic strokeEarly administration of aspirin minimizes the cerebral damage due to the incident strokeHeparin should be considered in pts with progressive symptomsDexamethasone is standard care for large infarcts with progressive symptoms76. TIATo diagnose according to the new criteria a brain scan is requiredTIA with transient weakness is more likely to lead a disabling stroke than a TIA causing amaurosis fugaxEarly investigation is the key to preventing a strokeCHAD score helps prognosticate TIAsIf a pt with TIA has 99% occlusioj of the corresponding ICA he should be heparinised77. CI for thrombolysis includeCurrent aspirin useBeing on warfarinA minor stroke 1 month beforeAge over 80yrsDemonstrable clot occluding the ICA78.Parkinson’s diseaseBradykinesia is a typical featureHas a better prognosis than MSAHearing impairment may preceed motor symptomsSense of smell is often affected in PDEarly memory impairment suggests alternative diagnosis79. MSAThose with early autonomic dysfunction have a worse prognosisDiagnosis is made clinicallyMRI is helpful in the evaluation Humming bird sign is seen in MRIAnal sphincter EMG may show denervation changes80.TremorParkinsonian tremor is the most disabling type of tremorAction tremor is typically seen in essential tremorIntention tremor is seen in cerebellar diseaseBetablockers are very effective in controlling intention tremorOrthostatic tremor responds to clonazepam81. SleepHypersomnolence is the most common sleep disorderMost of adult sleep is in REMNormal person has about 10 sleep cycles every night Dreaming occurs in REMSleep walking occurs in NREM82. Subacute combined degeneration of the spinal cord80% of pts with pernicious anaemia suffer from this neurological conditionMost pts have associated megaloblastic anaemiaIs excluded if the pt has a normal Hb levelClinical features are caued by demyelination of posterior columns and spinothalamic tractsSphincters may get involved in later stagesCopper deficiency could present with similar clinical findings

HypercalcaemiaOf primary hyperparathyroidism readily responds to steroidsCan be due to familial hypocalciuria when presents with recurrent renal stonesBone pain is typical of primary hyperparathyroidismThey can present with peptic ulcersForced dieresis and hydration are key RX51.WOF type of arthritis is not seen in psoriatic arthritisSymmetrical small joint arthropathyJaccoud’s arthropathySacroilitisMonoarthritisDIP joint arthropathy52. WOF is not aarecognized factor for osteoporosisEarly menarcheSmokingLow dietary calcium intakeSedentary lifestyleSlender body habbitus53. Following are recognized extra articular manifestations of rheumatoid arthritis exceptCaplans syndromePyoderma gangrenosumPhotosensitive rashScleromalacia perforansPeripheral neuropathy54.Following are poor prognostic factors in RA exceptPersistent synovitisEarly erosive changesExtra articular findingsNegative anti-CCP antibodiesPositive rheumatoid factor55. Features of temporal arteritis includeHeadacheNormal ESRScalp tendernessFeverJaw claudication56.Recognized side effects of steroid use includeAtypical features of infectionsProximal myopathyChronic pancreatitisAvascula necrosis of boneBone marrow suppression57. recogniozed side effects of MTX includeCirrhosisBM suppressionMouth ulcersAcute interstitial pneumonitisMaculopathy58. An 80 yr old male presented with painful swelling of his left knee joint of 2 weeks duration. A knee joint effusion was detected on examination.waht is the most likely causePseudogout of the kneeTrauma to the kneeSeptic arthritis of the kneeRheumatoid arthritis of the kneeOsteoarthritis of the knee59. Following are red flag signs of backache in a 60 yr old femalePain when getting up from the seated positionPresence of fever and weight lossShooting pain down the right legAssociation with bladder symptomsWorse early morning60. WOF are beneficial in Rx in acute goutColchicineAllopurinolCorticosteroidsNSAIDs Febuxostat61. A coronary angiogram with a view to revascularization is indicated inAll post infarct ptsA positive exercise ECG at a high workload not on anti anginal medicationAll unstable angina ptsAcute anterior STEMI with CI to thrombolyticsCardiogenic shock due to post MI VSD62. Recognized causes of sinus bradycardia includeHypoglycaemiaCholestatic jaundiceMyocarditisDigitalis toxicityRaised ICP63. Drugs safe to use in AF with WPW syndrome include the followingDigoxinVerapamilAmiodaroneSotalolFlecainide64. Acuired prolonged QT interval is known to be caused byHypercalcaemiaHypomagnesaemiaHyperkalaemiaAstemazole Erythromycin65. T/F regarding thrombolytic therapy in acute MIThrombolysis within 12 hours reduces ventricular damage and mortality rateActs in synergy with aspirin 150-300mg chewedTissue type plasminogen activator achieves higher reperfusion rates than skIV heparin therapy is mandatory after sk therapyPrimary PCI achieves higher reperfusion rates than thrombolytics66. Drugs known to prolong survival in unstable angina includeNitratesBeta blockersACEILMWHClopidogrel67. Following are known to prolong survival in acute MIPrimaty angioplastyACEIAspirinBeta blockersStatin68.T/F regarding coronary artery disease preventionGoal LDL cholesterol level for secondary prevention is <130mg/dlGoal LDL level for primary CAD prevention in diabetics is <160mg/dlGoal BP for diabetics is 140/90Goal LDL for primary CAD prevention in a hypertensive and a smoker is<130mg/dlStatin therapy is beneficial immediate post MI irrespective of the cholesterol level69. Drugs used in the primary prevention of CAD includeAspirinStatinBeta blockersClopidogrelNitrates70. Drugs known to prolong survival in heart failure includeNitrates with hydralazineDigoxinACEIARBSIvabradine71. Treatments known to prolong survival in heart failure includeMetoprololEplerononeAICDCardiac resynchronization therapyCardiac transplant72. Recognized indications for warfarin therapy includeIntermittent AFMS with sinus rhythmAF with a TIAAF with HT and DMPrimary pulmonary hypertension73. T/F regarding LMWHFondaparinaux is superior in efficacy to enoxaparinA standard dose of fondaparinaux is given to all pts irrespective of their bosy weightDose adjustment is required in renal dysfunctionAnticoagulant effect can be reversed with protamineLevel of anticoagulation can be monitored with activated factor x levels[Xa]74.Regarding severe hypercalcaemiaSymptoms occur when serum calcium is >3mmol/lRarely can present as comaST segment depression responsive to Rx of hypercalcaemia may be seenCalcitonin is the first line RX in MxGlucocorticoids should be considered in pts with vitamin D dependent hypercalcaemia75. Ischaemic strokeCan be reliably diagnosed at the bedside by a neurologist Surgery may be indicated in some pts with ischaemic strokeEarly administration of aspirin minimizes the cerebral damage due to the incident strokeHeparin should be considered in pts with progressive symptomsDexamethasone is standard care for large infarcts with progressive symptoms76. TIATo diagnose according to the new criteria a brain scan is requiredTIA with transient weakness is more likely to lead a disabling stroke than a TIA causing amaurosis fugaxEarly investigation is the key to preventing a strokeCHAD score helps prognosticate TIAsIf a pt with TIA has 99% occlusioj of the corresponding ICA he should be heparinised77. CI for thrombolysis includeCurrent aspirin useBeing on warfarinA minor stroke 1 month beforeAge over 80yrsDemonstrable clot occluding the ICA78.Parkinson’s diseaseBradykinesia is a typical featureHas a better prognosis than MSAHearing impairment may preceed motor symptomsSense of smell is often affected in PDEarly memory impairment suggests alternative diagnosis79. MSAThose with early autonomic dysfunction have a worse prognosisDiagnosis is made clinicallyMRI is helpful in the evaluation Humming bird sign is seen in MRIAnal sphincter EMG may show denervation changes80.TremorParkinsonian tremor is the most disabling type of tremorAction tremor is typically seen in essential tremorIntention tremor is seen in cerebellar diseaseBetablockers are very effective in controlling intention tremorOrthostatic tremor responds to clonazepam81. SleepHypersomnolence is the most common sleep disorderMost of adult sleep is in REMNormal person has about 10 sleep cycles every night Dreaming occurs in REMSleep walking occurs in NREM82. Subacute combined degeneration of the spinal cord80% of pts with pernicious anaemia suffer from this neurological conditionMost pts have associated megaloblastic anaemiaIs excluded if the pt has a normal Hb levelClinical features are caued by demyelination of posterior columns and spinothalamic tractsSphincters may get involved in later stagesCopper deficiency could present with similar clinical findings

HypercalcaemiaOf primary hyperparathyroidism readily responds to steroidsCan be due to familial hypocalciuria when presents with recurrent renal stonesBone pain is typical of primary hyperparathyroidismThey can present with peptic ulcersForced dieresis and hydration are key RX51.WOF type of arthritis is not seen in psoriatic arthritisSymmetrical small joint arthropathyJaccoud’s arthropathySacroilitisMonoarthritisDIP joint arthropathy52. WOF is not aarecognized factor for osteoporosisEarly menarcheSmokingLow dietary calcium intakeSedentary lifestyleSlender body habbitus53. Following are recognized extra articular manifestations of rheumatoid arthritis exceptCaplans syndromePyoderma gangrenosumPhotosensitive rashScleromalacia perforansPeripheral neuropathy54.Following are poor prognostic factors in RA exceptPersistent synovitisEarly erosive changesExtra articular findingsNegative anti-CCP antibodiesPositive rheumatoid factor55. Features of temporal arteritis includeHeadacheNormal ESRScalp tendernessFeverJaw claudication56.Recognized side effects of steroid use includeAtypical features of infectionsProximal myopathyChronic pancreatitisAvascula necrosis of boneBone marrow suppression57. recogniozed side effects of MTX includeCirrhosisBM suppressionMouth ulcersAcute interstitial pneumonitisMaculopathy58. An 80 yr old male presented with painful swelling of his left knee joint of 2 weeks duration. A knee joint effusion was detected on examination.waht is the most likely causePseudogout of the kneeTrauma to the kneeSeptic arthritis of the kneeRheumatoid arthritis of the kneeOsteoarthritis of the knee59. Following are red flag signs of backache in a 60 yr old femalePain when getting up from the seated positionPresence of fever and weight lossShooting pain down the right legAssociation with bladder symptomsWorse early morning60. WOF are beneficial in Rx in acute goutColchicineAllopurinolCorticosteroidsNSAIDs Febuxostat61. A coronary angiogram with a view to revascularization is indicated inAll post infarct ptsA positive exercise ECG at a high workload not on anti anginal medicationAll unstable angina ptsAcute anterior STEMI with CI to thrombolyticsCardiogenic shock due to post MI VSD62. Recognized causes of sinus bradycardia includeHypoglycaemiaCholestatic jaundiceMyocarditisDigitalis toxicityRaised ICP63. Drugs safe to use in AF with WPW syndrome include the followingDigoxinVerapamilAmiodaroneSotalolFlecainide64. Acuired prolonged QT interval is known to be caused byHypercalcaemiaHypomagnesaemiaHyperkalaemiaAstemazole Erythromycin65. T/F regarding thrombolytic therapy in acute MIThrombolysis within 12 hours reduces ventricular damage and mortality rateActs in synergy with aspirin 150-300mg chewedTissue type plasminogen activator achieves higher reperfusion rates than skIV heparin therapy is mandatory after sk therapyPrimary PCI achieves higher reperfusion rates than thrombolytics66. Drugs known to prolong survival in unstable angina includeNitratesBeta blockersACEILMWHClopidogrel67. Following are known to prolong survival in acute MIPrimaty angioplastyACEIAspirinBeta blockersStatin68.T/F regarding coronary artery disease preventionGoal LDL cholesterol level for secondary prevention is <130mg/dlGoal LDL level for primary CAD prevention in diabetics is <160mg/dlGoal BP for diabetics is 140/90Goal LDL for primary CAD prevention in a hypertensive and a smoker is<130mg/dlStatin therapy is beneficial immediate post MI irrespective of the cholesterol level69. Drugs used in the primary prevention of CAD includeAspirinStatinBeta blockersClopidogrelNitrates70. Drugs known to prolong survival in heart failure includeNitrates with hydralazineDigoxinACEIARBSIvabradine71. Treatments known to prolong survival in heart failure includeMetoprololEplerononeAICDCardiac resynchronization therapyCardiac transplant72. Recognized indications for warfarin therapy includeIntermittent AFMS with sinus rhythmAF with a TIAAF with HT and DMPrimary pulmonary hypertension73. T/F regarding LMWHFondaparinaux is superior in efficacy to enoxaparinA standard dose of fondaparinaux is given to all pts irrespective of their bosy weightDose adjustment is required in renal dysfunctionAnticoagulant effect can be reversed with protamineLevel of anticoagulation can be monitored with activated factor x levels[Xa]74.Regarding severe hypercalcaemiaSymptoms occur when serum calcium is >3mmol/lRarely can present as comaST segment depression responsive to Rx of hypercalcaemia may be seenCalcitonin is the first line RX in MxGlucocorticoids should be considered in pts with vitamin D dependent hypercalcaemia75. Ischaemic strokeCan be reliably diagnosed at the bedside by a neurologist Surgery may be indicated in some pts with ischaemic strokeEarly administration of aspirin minimizes the cerebral damage due to the incident strokeHeparin should be considered in pts with progressive symptomsDexamethasone is standard care for large infarcts with progressive symptoms76. TIATo diagnose according to the new criteria a brain scan is requiredTIA with transient weakness is more likely to lead a disabling stroke than a TIA causing amaurosis fugaxEarly investigation is the key to preventing a strokeCHAD score helps prognosticate TIAsIf a pt with TIA has 99% occlusioj of the corresponding ICA he should be heparinised77. CI for thrombolysis includeCurrent aspirin useBeing on warfarinA minor stroke 1 month beforeAge over 80yrsDemonstrable clot occluding the ICA78.Parkinson’s diseaseBradykinesia is a typical featureHas a better prognosis than MSAHearing impairment may preceed motor symptomsSense of smell is often affected in PDEarly memory impairment suggests alternative diagnosis79. MSAThose with early autonomic dysfunction have a worse prognosisDiagnosis is made clinicallyMRI is helpful in the evaluation Humming bird sign is seen in MRIAnal sphincter EMG may show denervation changes80.TremorParkinsonian tremor is the most disabling type of tremorAction tremor is typically seen in essential tremorIntention tremor is seen in cerebellar diseaseBetablockers are very effective in controlling intention tremorOrthostatic tremor responds to clonazepam81. SleepHypersomnolence is the most common sleep disorderMost of adult sleep is in REMNormal person has about 10 sleep cycles every night Dreaming occurs in REMSleep walking occurs in NREM82. Subacute combined degeneration of the spinal cord80% of pts with pernicious anaemia suffer from this neurological conditionMost pts have associated megaloblastic anaemiaIs excluded if the pt has a normal Hb levelClinical features are caued by demyelination of posterior columns and spinothalamic tractsSphincters may get involved in later stagesCopper deficiency could present with similar clinical findings

HypercalcaemiaOf primary hyperparathyroidism readily responds to steroidsCan be due to familial hypocalciuria when presents with recurrent renal stonesBone pain is typical of primary hyperparathyroidismThey can present with peptic ulcersForced dieresis and hydration are key RX51.WOF type of arthritis is not seen in psoriatic arthritisSymmetrical small joint arthropathyJaccoud’s arthropathySacroilitisMonoarthritisDIP joint arthropathy52. WOF is not aarecognized factor for osteoporosisEarly menarcheSmokingLow dietary calcium intakeSedentary lifestyleSlender body habbitus53. Following are recognized extra articular manifestations of rheumatoid arthritis exceptCaplans syndromePyoderma gangrenosumPhotosensitive rashScleromalacia perforansPeripheral neuropathy54.Following are poor prognostic factors in RA exceptPersistent synovitisEarly erosive changesExtra articular findingsNegative anti-CCP antibodiesPositive rheumatoid factor55. Features of temporal arteritis includeHeadacheNormal ESRScalp tendernessFeverJaw claudication56.Recognized side effects of steroid use includeAtypical features of infectionsProximal myopathyChronic pancreatitisAvascula necrosis of boneBone marrow suppression57. recogniozed side effects of MTX includeCirrhosisBM suppressionMouth ulcersAcute interstitial pneumonitisMaculopathy58. An 80 yr old male presented with painful swelling of his left knee joint of 2 weeks duration. A knee joint effusion was detected on examination.waht is the most likely causePseudogout of the kneeTrauma to the kneeSeptic arthritis of the kneeRheumatoid arthritis of the kneeOsteoarthritis of the knee59. Following are red flag signs of backache in a 60 yr old femalePain when getting up from the seated positionPresence of fever and weight lossShooting pain down the right legAssociation with bladder symptomsWorse early morning60. WOF are beneficial in Rx in acute goutColchicineAllopurinolCorticosteroidsNSAIDs Febuxostat61. A coronary angiogram with a view to revascularization is indicated inAll post infarct ptsA positive exercise ECG at a high workload not on anti anginal medicationAll unstable angina ptsAcute anterior STEMI with CI to thrombolyticsCardiogenic shock due to post MI VSD62. Recognized causes of sinus bradycardia includeHypoglycaemiaCholestatic jaundiceMyocarditisDigitalis toxicityRaised ICP63. Drugs safe to use in AF with WPW syndrome include the followingDigoxinVerapamilAmiodaroneSotalolFlecainide64. Acuired prolonged QT interval is known to be caused byHypercalcaemiaHypomagnesaemiaHyperkalaemiaAstemazole Erythromycin65. T/F regarding thrombolytic therapy in acute MIThrombolysis within 12 hours reduces ventricular damage and mortality rateActs in synergy with aspirin 150-300mg chewedTissue type plasminogen activator achieves higher reperfusion rates than skIV heparin therapy is mandatory after sk therapyPrimary PCI achieves higher reperfusion rates than thrombolytics66. Drugs known to prolong survival in unstable angina includeNitratesBeta blockersACEILMWHClopidogrel67. Following are known to prolong survival in acute MIPrimaty angioplastyACEIAspirinBeta blockersStatin68.T/F regarding coronary artery disease preventionGoal LDL cholesterol level for secondary prevention is <130mg/dlGoal LDL level for primary CAD prevention in diabetics is <160mg/dlGoal BP for diabetics is 140/90Goal LDL for primary CAD prevention in a hypertensive and a smoker is<130mg/dlStatin therapy is beneficial immediate post MI irrespective of the cholesterol level69. Drugs used in the primary prevention of CAD includeAspirinStatinBeta blockersClopidogrelNitrates70. Drugs known to prolong survival in heart failure includeNitrates with hydralazineDigoxinACEIARBSIvabradine71. Treatments known to prolong survival in heart failure includeMetoprololEplerononeAICDCardiac resynchronization therapyCardiac transplant72. Recognized indications for warfarin therapy includeIntermittent AFMS with sinus rhythmAF with a TIAAF with HT and DMPrimary pulmonary hypertension73. T/F regarding LMWHFondaparinaux is superior in efficacy to enoxaparinA standard dose of fondaparinaux is given to all pts irrespective of their bosy weightDose adjustment is required in renal dysfunctionAnticoagulant effect can be reversed with protamineLevel of anticoagulation can be monitored with activated factor x levels[Xa]74.Regarding severe hypercalcaemiaSymptoms occur when serum calcium is >3mmol/lRarely can present as comaST segment depression responsive to Rx of hypercalcaemia may be seenCalcitonin is the first line RX in MxGlucocorticoids should be considered in pts with vitamin D dependent hypercalcaemia75. Ischaemic strokeCan be reliably diagnosed at the bedside by a neurologist Surgery may be indicated in some pts with ischaemic strokeEarly administration of aspirin minimizes the cerebral damage due to the incident strokeHeparin should be considered in pts with progressive symptomsDexamethasone is standard care for large infarcts with progressive symptoms76. TIATo diagnose according to the new criteria a brain scan is requiredTIA with transient weakness is more likely to lead a disabling stroke than a TIA causing amaurosis fugaxEarly investigation is the key to preventing a strokeCHAD score helps prognosticate TIAsIf a pt with TIA has 99% occlusioj of the corresponding ICA he should be heparinised77. CI for thrombolysis includeCurrent aspirin useBeing on warfarinA minor stroke 1 month beforeAge over 80yrsDemonstrable clot occluding the ICA78.Parkinson’s diseaseBradykinesia is a typical featureHas a better prognosis than MSAHearing impairment may preceed motor symptomsSense of smell is often affected in PDEarly memory impairment suggests alternative diagnosis79. MSAThose with early autonomic dysfunction have a worse prognosisDiagnosis is made clinicallyMRI is helpful in the evaluation Humming bird sign is seen in MRIAnal sphincter EMG may show denervation changes80.TremorParkinsonian tremor is the most disabling type of tremorAction tremor is typically seen in essential tremorIntention tremor is seen in cerebellar diseaseBetablockers are very effective in controlling intention tremorOrthostatic tremor responds to clonazepam81. SleepHypersomnolence is the most common sleep disorderMost of adult sleep is in REMNormal person has about 10 sleep cycles every night Dreaming occurs in REMSleep walking occurs in NREM82. Subacute combined degeneration of the spinal cord80% of pts with pernicious anaemia suffer from this neurological conditionMost pts have associated megaloblastic anaemiaIs excluded if the pt has a normal Hb levelClinical features are caued by demyelination of posterior columns and spinothalamic tractsSphincters may get involved in later stagesCopper deficiency could present with similar clinical findings

HypercalcaemiaOf primary hyperparathyroidism readily responds to steroidsCan be due to familial hypocalciuria when presents with recurrent renal stonesBone pain is typical of primary hyperparathyroidismThey can present with peptic ulcersForced dieresis and hydration are key RX51.WOF type of arthritis is not seen in psoriatic arthritisSymmetrical small joint arthropathyJaccoud’s arthropathySacroilitisMonoarthritisDIP joint arthropathy52. WOF is not aarecognized factor for osteoporosisEarly menarcheSmokingLow dietary calcium intakeSedentary lifestyleSlender body habbitus53. Following are recognized extra articular manifestations of rheumatoid arthritis exceptCaplans syndromePyoderma gangrenosumPhotosensitive rashScleromalacia perforansPeripheral neuropathy54.Following are poor prognostic factors in RA exceptPersistent synovitisEarly erosive changesExtra articular findingsNegative anti-CCP antibodiesPositive rheumatoid factor55. Features of temporal arteritis includeHeadacheNormal ESRScalp tendernessFeverJaw claudication56.Recognized side effects of steroid use includeAtypical features of infectionsProximal myopathyChronic pancreatitisAvascula necrosis of boneBone marrow suppression57. recogniozed side effects of MTX includeCirrhosisBM suppressionMouth ulcersAcute interstitial pneumonitisMaculopathy58. An 80 yr old male presented with painful swelling of his left knee joint of 2 weeks duration. A knee joint effusion was detected on examination.waht is the most likely causePseudogout of the kneeTrauma to the kneeSeptic arthritis of the kneeRheumatoid arthritis of the kneeOsteoarthritis of the knee59. Following are red flag signs of backache in a 60 yr old femalePain when getting up from the seated positionPresence of fever and weight lossShooting pain down the right legAssociation with bladder symptomsWorse early morning60. WOF are beneficial in Rx in acute goutColchicineAllopurinolCorticosteroidsNSAIDs Febuxostat61. A coronary angiogram with a view to revascularization is indicated inAll post infarct ptsA positive exercise ECG at a high workload not on anti anginal medicationAll unstable angina ptsAcute anterior STEMI with CI to thrombolyticsCardiogenic shock due to post MI VSD62. Recognized causes of sinus bradycardia includeHypoglycaemiaCholestatic jaundiceMyocarditisDigitalis toxicityRaised ICP63. Drugs safe to use in AF with WPW syndrome include the followingDigoxinVerapamilAmiodaroneSotalolFlecainide64. Acuired prolonged QT interval is known to be caused byHypercalcaemiaHypomagnesaemiaHyperkalaemiaAstemazole Erythromycin65. T/F regarding thrombolytic therapy in acute MIThrombolysis within 12 hours reduces ventricular damage and mortality rateActs in synergy with aspirin 150-300mg chewedTissue type plasminogen activator achieves higher reperfusion rates than skIV heparin therapy is mandatory after sk therapyPrimary PCI achieves higher reperfusion rates than thrombolytics66. Drugs known to prolong survival in unstable angina includeNitratesBeta blockersACEILMWHClopidogrel67. Following are known to prolong survival in acute MIPrimaty angioplastyACEIAspirinBeta blockersStatin68.T/F regarding coronary artery disease preventionGoal LDL cholesterol level for secondary prevention is <130mg/dlGoal LDL level for primary CAD prevention in diabetics is <160mg/dlGoal BP for diabetics is 140/90Goal LDL for primary CAD prevention in a hypertensive and a smoker is<130mg/dlStatin therapy is beneficial immediate post MI irrespective of the cholesterol level69. Drugs used in the primary prevention of CAD includeAspirinStatinBeta blockersClopidogrelNitrates70. Drugs known to prolong survival in heart failure includeNitrates with hydralazineDigoxinACEIARBSIvabradine71. Treatments known to prolong survival in heart failure includeMetoprololEplerononeAICDCardiac resynchronization therapyCardiac transplant72. Recognized indications for warfarin therapy includeIntermittent AFMS with sinus rhythmAF with a TIAAF with HT and DMPrimary pulmonary hypertension73. T/F regarding LMWHFondaparinaux is superior in efficacy to enoxaparinA standard dose of fondaparinaux is given to all pts irrespective of their bosy weightDose adjustment is required in renal dysfunctionAnticoagulant effect can be reversed with protamineLevel of anticoagulation can be monitored with activated factor x levels[Xa]74.Regarding severe hypercalcaemiaSymptoms occur when serum calcium is >3mmol/lRarely can present as comaST segment depression responsive to Rx of hypercalcaemia may be seenCalcitonin is the first line RX in MxGlucocorticoids should be considered in pts with vitamin D dependent hypercalcaemia75. Ischaemic strokeCan be reliably diagnosed at the bedside by a neurologist Surgery may be indicated in some pts with ischaemic strokeEarly administration of aspirin minimizes the cerebral damage due to the incident strokeHeparin should be considered in pts with progressive symptomsDexamethasone is standard care for large infarcts with progressive symptoms76. TIATo diagnose according to the new criteria a brain scan is requiredTIA with transient weakness is more likely to lead a disabling stroke than a TIA causing amaurosis fugaxEarly investigation is the key to preventing a strokeCHAD score helps prognosticate TIAsIf a pt with TIA has 99% occlusioj of the corresponding ICA he should be heparinised77. CI for thrombolysis includeCurrent aspirin useBeing on warfarinA minor stroke 1 month beforeAge over 80yrsDemonstrable clot occluding the ICA78.Parkinson’s diseaseBradykinesia is a typical featureHas a better prognosis than MSAHearing impairment may preceed motor symptomsSense of smell is often affected in PDEarly memory impairment suggests alternative diagnosis79. MSAThose with early autonomic dysfunction have a worse prognosisDiagnosis is made clinicallyMRI is helpful in the evaluation Humming bird sign is seen in MRIAnal sphincter EMG may show denervation changes80.TremorParkinsonian tremor is the most disabling type of tremorAction tremor is typically seen in essential tremorIntention tremor is seen in cerebellar diseaseBetablockers are very effective in controlling intention tremorOrthostatic tremor responds to clonazepam81. SleepHypersomnolence is the most common sleep disorderMost of adult sleep is in REMNormal person has about 10 sleep cycles every night Dreaming occurs in REMSleep walking occurs in NREM82. Subacute combined degeneration of the spinal cord80% of pts with pernicious anaemia suffer from this neurological conditionMost pts have associated megaloblastic anaemiaIs excluded if the pt has a normal Hb levelClinical features are caued by demyelination of posterior columns and spinothalamic tractsSphincters may get involved in later stagesCopper deficiency could present with similar clinical findings

HypercalcaemiaOf primary hyperparathyroidism readily responds to steroidsCan be due to familial hypocalciuria when presents with recurrent renal stonesBone pain is typical of primary hyperparathyroidismThey can present with peptic ulcersForced dieresis and hydration are key RX51.WOF type of arthritis is not seen in psoriatic arthritisSymmetrical small joint arthropathyJaccoud’s arthropathySacroilitisMonoarthritisDIP joint arthropathy52. WOF is not aarecognized factor for osteoporosisEarly menarcheSmokingLow dietary calcium intakeSedentary lifestyleSlender body habbitus53. Following are recognized extra articular manifestations of rheumatoid arthritis exceptCaplans syndromePyoderma gangrenosumPhotosensitive rashScleromalacia perforansPeripheral neuropathy54.Following are poor prognostic factors in RA exceptPersistent synovitisEarly erosive changesExtra articular findingsNegative anti-CCP antibodiesPositive rheumatoid factor55. Features of temporal arteritis includeHeadacheNormal ESRScalp tendernessFeverJaw claudication56.Recognized side effects of steroid use includeAtypical features of infectionsProximal myopathyChronic pancreatitisAvascula necrosis of boneBone marrow suppression57. recogniozed side effects of MTX includeCirrhosisBM suppressionMouth ulcersAcute interstitial pneumonitisMaculopathy58. An 80 yr old male presented with painful swelling of his left knee joint of 2 weeks duration. A knee joint effusion was detected on examination.waht is the most likely causePseudogout of the kneeTrauma to the kneeSeptic arthritis of the kneeRheumatoid arthritis of the kneeOsteoarthritis of the knee59. Following are red flag signs of backache in a 60 yr old femalePain when getting up from the seated positionPresence of fever and weight lossShooting pain down the right legAssociation with bladder symptomsWorse early morning60. WOF are beneficial in Rx in acute goutColchicineAllopurinolCorticosteroidsNSAIDs Febuxostat61. A coronary angiogram with a view to revascularization is indicated inAll post infarct ptsA positive exercise ECG at a high workload not on anti anginal medicationAll unstable angina ptsAcute anterior STEMI with CI to thrombolyticsCardiogenic shock due to post MI VSD62. Recognized causes of sinus bradycardia includeHypoglycaemiaCholestatic jaundiceMyocarditisDigitalis toxicityRaised ICP63. Drugs safe to use in AF with WPW syndrome include the followingDigoxinVerapamilAmiodaroneSotalolFlecainide64. Acuired prolonged QT interval is known to be caused byHypercalcaemiaHypomagnesaemiaHyperkalaemiaAstemazole Erythromycin65. T/F regarding thrombolytic therapy in acute MIThrombolysis within 12 hours reduces ventricular damage and mortality rateActs in synergy with aspirin 150-300mg chewedTissue type plasminogen activator achieves higher reperfusion rates than skIV heparin therapy is mandatory after sk therapyPrimary PCI achieves higher reperfusion rates than thrombolytics66. Drugs known to prolong survival in unstable angina includeNitratesBeta blockersACEILMWHClopidogrel67. Following are known to prolong survival in acute MIPrimaty angioplastyACEIAspirinBeta blockersStatin68.T/F regarding coronary artery disease preventionGoal LDL cholesterol level for secondary prevention is <130mg/dlGoal LDL level for primary CAD prevention in diabetics is <160mg/dlGoal BP for diabetics is 140/90Goal LDL for primary CAD prevention in a hypertensive and a smoker is<130mg/dlStatin therapy is beneficial immediate post MI irrespective of the cholesterol level69. Drugs used in the primary prevention of CAD includeAspirinStatinBeta blockersClopidogrelNitrates70. Drugs known to prolong survival in heart failure includeNitrates with hydralazineDigoxinACEIARBSIvabradine71. Treatments known to prolong survival in heart failure includeMetoprololEplerononeAICDCardiac resynchronization therapyCardiac transplant72. Recognized indications for warfarin therapy includeIntermittent AFMS with sinus rhythmAF with a TIAAF with HT and DMPrimary pulmonary hypertension73. T/F regarding LMWHFondaparinaux is superior in efficacy to enoxaparinA standard dose of fondaparinaux is given to all pts irrespective of their bosy weightDose adjustment is required in renal dysfunctionAnticoagulant effect can be reversed with protamineLevel of anticoagulation can be monitored with activated factor x levels[Xa]74.Regarding severe hypercalcaemiaSymptoms occur when serum calcium is >3mmol/lRarely can present as comaST segment depression responsive to Rx of hypercalcaemia may be seenCalcitonin is the first line RX in MxGlucocorticoids should be considered in pts with vitamin D dependent hypercalcaemia75. Ischaemic strokeCan be reliably diagnosed at the bedside by a neurologist Surgery may be indicated in some pts with ischaemic strokeEarly administration of aspirin minimizes the cerebral damage due to the incident strokeHeparin should be considered in pts with progressive symptomsDexamethasone is standard care for large infarcts with progressive symptoms76. TIATo diagnose according to the new criteria a brain scan is requiredTIA with transient weakness is more likely to lead a disabling stroke than a TIA causing amaurosis fugaxEarly investigation is the key to preventing a strokeCHAD score helps prognosticate TIAsIf a pt with TIA has 99% occlusioj of the corresponding ICA he should be heparinised77. CI for thrombolysis includeCurrent aspirin useBeing on warfarinA minor stroke 1 month beforeAge over 80yrsDemonstrable clot occluding the ICA78.Parkinson’s diseaseBradykinesia is a typical featureHas a better prognosis than MSAHearing impairment may preceed motor symptomsSense of smell is often affected in PDEarly memory impairment suggests alternative diagnosis79. MSAThose with early autonomic dysfunction have a worse prognosisDiagnosis is made clinicallyMRI is helpful in the evaluation Humming bird sign is seen in MRIAnal sphincter EMG may show denervation changes80.TremorParkinsonian tremor is the most disabling type of tremorAction tremor is typically seen in essential tremorIntention tremor is seen in cerebellar diseaseBetablockers are very effective in controlling intention tremorOrthostatic tremor responds to clonazepam81. SleepHypersomnolence is the most common sleep disorderMost of adult sleep is in REMNormal person has about 10 sleep cycles every night Dreaming occurs in REMSleep walking occurs in NREM82. Subacute combined degeneration of the spinal cord80% of pts with pernicious anaemia suffer from this neurological conditionMost pts have associated megaloblastic anaemiaIs excluded if the pt has a normal Hb levelClinical features are caued by demyelination of posterior columns and spinothalamic tractsSphincters may get involved in later stagesCopper deficiency could present with similar clinical findings

HypercalcaemiaOf primary hyperparathyroidism readily responds to steroidsCan be due to familial hypocalciuria when presents with recurrent renal stonesBone pain is typical of primary hyperparathyroidismThey can present with peptic ulcersForced dieresis and hydration are key RX51.WOF type of arthritis is not seen in psoriatic arthritisSymmetrical small joint arthropathyJaccoud’s arthropathySacroilitisMonoarthritisDIP joint arthropathy52. WOF is not aarecognized factor for osteoporosisEarly menarcheSmokingLow dietary calcium intakeSedentary lifestyleSlender body habbitus53. Following are recognized extra articular manifestations of rheumatoid arthritis exceptCaplans syndromePyoderma gangrenosumPhotosensitive rashScleromalacia perforansPeripheral neuropathy54.Following are poor prognostic factors in RA exceptPersistent synovitisEarly erosive changesExtra articular findingsNegative anti-CCP antibodiesPositive rheumatoid factor55. Features of temporal arteritis includeHeadacheNormal ESRScalp tendernessFeverJaw claudication56.Recognized side effects of steroid use includeAtypical features of infectionsProximal myopathyChronic pancreatitisAvascula necrosis of boneBone marrow suppression57. recogniozed side effects of MTX includeCirrhosisBM suppressionMouth ulcersAcute interstitial pneumonitisMaculopathy58. An 80 yr old male presented with painful swelling of his left knee joint of 2 weeks duration. A knee joint effusion was detected on examination.waht is the most likely causePseudogout of the kneeTrauma to the kneeSeptic arthritis of the kneeRheumatoid arthritis of the kneeOsteoarthritis of the knee59. Following are red flag signs of backache in a 60 yr old femalePain when getting up from the seated positionPresence of fever and weight lossShooting pain down the right legAssociation with bladder symptomsWorse early morning60. WOF are beneficial in Rx in acute goutColchicineAllopurinolCorticosteroidsNSAIDs Febuxostat61. A coronary angiogram with a view to revascularization is indicated inAll post infarct ptsA positive exercise ECG at a high workload not on anti anginal medicationAll unstable angina ptsAcute anterior STEMI with CI to thrombolyticsCardiogenic shock due to post MI VSD62. Recognized causes of sinus bradycardia includeHypoglycaemiaCholestatic jaundiceMyocarditisDigitalis toxicityRaised ICP63. Drugs safe to use in AF with WPW syndrome include the followingDigoxinVerapamilAmiodaroneSotalolFlecainide64. Acuired prolonged QT interval is known to be caused byHypercalcaemiaHypomagnesaemiaHyperkalaemiaAstemazole Erythromycin65. T/F regarding thrombolytic therapy in acute MIThrombolysis within 12 hours reduces ventricular damage and mortality rateActs in synergy with aspirin 150-300mg chewedTissue type plasminogen activator achieves higher reperfusion rates than skIV heparin therapy is mandatory after sk therapyPrimary PCI achieves higher reperfusion rates than thrombolytics66. Drugs known to prolong survival in unstable angina includeNitratesBeta blockersACEILMWHClopidogrel67. Following are known to prolong survival in acute MIPrimaty angioplastyACEIAspirinBeta blockersStatin68.T/F regarding coronary artery disease preventionGoal LDL cholesterol level for secondary prevention is <130mg/dlGoal LDL level for primary CAD prevention in diabetics is <160mg/dlGoal BP for diabetics is 140/90Goal LDL for primary CAD prevention in a hypertensive and a smoker is<130mg/dlStatin therapy is beneficial immediate post MI irrespective of the cholesterol level69. Drugs used in the primary prevention of CAD includeAspirinStatinBeta blockersClopidogrelNitrates70. Drugs known to prolong survival in heart failure includeNitrates with hydralazineDigoxinACEIARBSIvabradine71. Treatments known to prolong survival in heart failure includeMetoprololEplerononeAICDCardiac resynchronization therapyCardiac transplant72. Recognized indications for warfarin therapy includeIntermittent AFMS with sinus rhythmAF with a TIAAF with HT and DMPrimary pulmonary hypertension73. T/F regarding LMWHFondaparinaux is superior in efficacy to enoxaparinA standard dose of fondaparinaux is given to all pts irrespective of their bosy weightDose adjustment is required in renal dysfunctionAnticoagulant effect can be reversed with protamineLevel of anticoagulation can be monitored with activated factor x levels[Xa]74.Regarding severe hypercalcaemiaSymptoms occur when serum calcium is >3mmol/lRarely can present as comaST segment depression responsive to Rx of hypercalcaemia may be seenCalcitonin is the first line RX in MxGlucocorticoids should be considered in pts with vitamin D dependent hypercalcaemia75. Ischaemic strokeCan be reliably diagnosed at the bedside by a neurologist Surgery may be indicated in some pts with ischaemic strokeEarly administration of aspirin minimizes the cerebral damage due to the incident strokeHeparin should be considered in pts with progressive symptomsDexamethasone is standard care for large infarcts with progressive symptoms76. TIATo diagnose according to the new criteria a brain scan is requiredTIA with transient weakness is more likely to lead a disabling stroke than a TIA causing amaurosis fugaxEarly investigation is the key to preventing a strokeCHAD score helps prognosticate TIAsIf a pt with TIA has 99% occlusioj of the corresponding ICA he should be heparinised77. CI for thrombolysis includeCurrent aspirin useBeing on warfarinA minor stroke 1 month beforeAge over 80yrsDemonstrable clot occluding the ICA78.Parkinson’s diseaseBradykinesia is a typical featureHas a better prognosis than MSAHearing impairment may preceed motor symptomsSense of smell is often affected in PDEarly memory impairment suggests alternative diagnosis79. MSAThose with early autonomic dysfunction have a worse prognosisDiagnosis is made clinicallyMRI is helpful in the evaluation Humming bird sign is seen in MRIAnal sphincter EMG may show denervation changes80.TremorParkinsonian tremor is the most disabling type of tremorAction tremor is typically seen in essential tremorIntention tremor is seen in cerebellar diseaseBetablockers are very effective in controlling intention tremorOrthostatic tremor responds to clonazepam81. SleepHypersomnolence is the most common sleep disorderMost of adult sleep is in REMNormal person has about 10 sleep cycles every night Dreaming occurs in REMSleep walking occurs in NREM82. Subacute combined degeneration of the spinal cord80% of pts with pernicious anaemia suffer from this neurological conditionMost pts have associated megaloblastic anaemiaIs excluded if the pt has a normal Hb levelClinical features are caued by demyelination of posterior columns and spinothalamic tractsSphincters may get involved in later stagesCopper deficiency could present with similar clinical findings

HypercalcaemiaOf primary hyperparathyroidism readily responds to steroidsCan be due to familial hypocalciuria when presents with recurrent renal stonesBone pain is typical of primary hyperparathyroidismThey can present with peptic ulcersForced dieresis and hydration are key RX51.WOF type of arthritis is not seen in psoriatic arthritisSymmetrical small joint arthropathyJaccoud’s arthropathySacroilitisMonoarthritisDIP joint arthropathy52. WOF is not aarecognized factor for osteoporosisEarly menarcheSmokingLow dietary calcium intakeSedentary lifestyleSlender body habbitus53. Following are recognized extra articular manifestations of rheumatoid arthritis exceptCaplans syndromePyoderma gangrenosumPhotosensitive rashScleromalacia perforansPeripheral neuropathy54.Following are poor prognostic factors in RA exceptPersistent synovitisEarly erosive changesExtra articular findingsNegative anti-CCP antibodiesPositive rheumatoid factor55. Features of temporal arteritis includeHeadacheNormal ESRScalp tendernessFeverJaw claudication56.Recognized side effects of steroid use includeAtypical features of infectionsProximal myopathyChronic pancreatitisAvascula necrosis of boneBone marrow suppression57. recogniozed side effects of MTX includeCirrhosisBM suppressionMouth ulcersAcute interstitial pneumonitisMaculopathy58. An 80 yr old male presented with painful swelling of his left knee joint of 2 weeks duration. A knee joint effusion was detected on examination.waht is the most likely causePseudogout of the kneeTrauma to the kneeSeptic arthritis of the kneeRheumatoid arthritis of the kneeOsteoarthritis of the knee59. Following are red flag signs of backache in a 60 yr old femalePain when getting up from the seated positionPresence of fever and weight lossShooting pain down the right legAssociation with bladder symptomsWorse early morning60. WOF are beneficial in Rx in acute goutColchicineAllopurinolCorticosteroidsNSAIDs Febuxostat61. A coronary angiogram with a view to revascularization is indicated inAll post infarct ptsA positive exercise ECG at a high workload not on anti anginal medicationAll unstable angina ptsAcute anterior STEMI with CI to thrombolyticsCardiogenic shock due to post MI VSD62. Recognized causes of sinus bradycardia includeHypoglycaemiaCholestatic jaundiceMyocarditisDigitalis toxicityRaised ICP63. Drugs safe to use in AF with WPW syndrome include the followingDigoxinVerapamilAmiodaroneSotalolFlecainide64. Acuired prolonged QT interval is known to be caused byHypercalcaemiaHypomagnesaemiaHyperkalaemiaAstemazole Erythromycin65. T/F regarding thrombolytic therapy in acute MIThrombolysis within 12 hours reduces ventricular damage and mortality rateActs in synergy with aspirin 150-300mg chewedTissue type plasminogen activator achieves higher reperfusion rates than skIV heparin therapy is mandatory after sk therapyPrimary PCI achieves higher reperfusion rates than thrombolytics66. Drugs known to prolong survival in unstable angina includeNitratesBeta blockersACEILMWHClopidogrel67. Following are known to prolong survival in acute MIPrimaty angioplastyACEIAspirinBeta blockersStatin68.T/F regarding coronary artery disease preventionGoal LDL cholesterol level for secondary prevention is <130mg/dlGoal LDL level for primary CAD prevention in diabetics is <160mg/dlGoal BP for diabetics is 140/90Goal LDL for primary CAD prevention in a hypertensive and a smoker is<130mg/dlStatin therapy is beneficial immediate post MI irrespective of the cholesterol level69. Drugs used in the primary prevention of CAD includeAspirinStatinBeta blockersClopidogrelNitrates70. Drugs known to prolong survival in heart failure includeNitrates with hydralazineDigoxinACEIARBSIvabradine71. Treatments known to prolong survival in heart failure includeMetoprololEplerononeAICDCardiac resynchronization therapyCardiac transplant72. Recognized indications for warfarin therapy includeIntermittent AFMS with sinus rhythmAF with a TIAAF with HT and DMPrimary pulmonary hypertension73. T/F regarding LMWHFondaparinaux is superior in efficacy to enoxaparinA standard dose of fondaparinaux is given to all pts irrespective of their bosy weightDose adjustment is required in renal dysfunctionAnticoagulant effect can be reversed with protamineLevel of anticoagulation can be monitored with activated factor x levels[Xa]74.Regarding severe hypercalcaemiaSymptoms occur when serum calcium is >3mmol/lRarely can present as comaST segment depression responsive to Rx of hypercalcaemia may be seenCalcitonin is the first line RX in MxGlucocorticoids should be considered in pts with vitamin D dependent hypercalcaemia75. Ischaemic strokeCan be reliably diagnosed at the bedside by a neurologist Surgery may be indicated in some pts with ischaemic strokeEarly administration of aspirin minimizes the cerebral damage due to the incident strokeHeparin should be considered in pts with progressive symptomsDexamethasone is standard care for large infarcts with progressive symptoms76. TIATo diagnose according to the new criteria a brain scan is requiredTIA with transient weakness is more likely to lead a disabling stroke than a TIA causing amaurosis fugaxEarly investigation is the key to preventing a strokeCHAD score helps prognosticate TIAsIf a pt with TIA has 99% occlusioj of the corresponding ICA he should be heparinised77. CI for thrombolysis includeCurrent aspirin useBeing on warfarinA minor stroke 1 month beforeAge over 80yrsDemonstrable clot occluding the ICA78.Parkinson’s diseaseBradykinesia is a typical featureHas a better prognosis than MSAHearing impairment may preceed motor symptomsSense of smell is often affected in PDEarly memory impairment suggests alternative diagnosis79. MSAThose with early autonomic dysfunction have a worse prognosisDiagnosis is made clinicallyMRI is helpful in the evaluation Humming bird sign is seen in MRIAnal sphincter EMG may show denervation changes80.TremorParkinsonian tremor is the most disabling type of tremorAction tremor is typically seen in essential tremorIntention tremor is seen in cerebellar diseaseBetablockers are very effective in controlling intention tremorOrthostatic tremor responds to clonazepam81. SleepHypersomnolence is the most common sleep disorderMost of adult sleep is in REMNormal person has about 10 sleep cycles every night Dreaming occurs in REMSleep walking occurs in NREM82. Subacute combined degeneration of the spinal cord80% of pts with pernicious anaemia suffer from this neurological conditionMost pts have associated megaloblastic anaemiaIs excluded if the pt has a normal Hb levelClinical features are caued by demyelination of posterior columns and spinothalamic tractsSphincters may get involved in later stagesCopper deficiency could present with similar clinical findings

HypercalcaemiaOf primary hyperparathyroidism readily responds to steroidsCan be due to familial hypocalciuria when presents with recurrent renal stonesBone pain is typical of primary hyperparathyroidismThey can present with peptic ulcersForced dieresis and hydration are key RX51.WOF type of arthritis is not seen in psoriatic arthritisSymmetrical small joint arthropathyJaccoud’s arthropathySacroilitisMonoarthritisDIP joint arthropathy52. WOF is not aarecognized factor for osteoporosisEarly menarcheSmokingLow dietary calcium intakeSedentary lifestyleSlender body habbitus53. Following are recognized extra articular manifestations of rheumatoid arthritis exceptCaplans syndromePyoderma gangrenosumPhotosensitive rashScleromalacia perforansPeripheral neuropathy54.Following are poor prognostic factors in RA exceptPersistent synovitisEarly erosive changesExtra articular findingsNegative anti-CCP antibodiesPositive rheumatoid factor55. Features of temporal arteritis includeHeadacheNormal ESRScalp tendernessFeverJaw claudication56.Recognized side effects of steroid use includeAtypical features of infectionsProximal myopathyChronic pancreatitisAvascula necrosis of boneBone marrow suppression

Back 6

Ok

Front 7

Polymyalgia rheumatic:

Proximal muscle weakness

High CPK

Associated with malignancy 🚀

Common in fourth decadem

High ALP

Back 7

Can be associated with malignancy

Front 8

Angiotensin:🚀

Secrete vasopressin

Secrete noradrenalin

Constrict efferent arterioles

Sodium and water resorption

Diuresis

Back 8

Angiotensin II (Ang II), a potent vasoconstrictor, stimulates the formation and secretion of aldosterone from the adrenal gland, and has pleiotropic effects on cellular growth.

The majority of Ang II is derived from the precursor angiotensin I (Ang I), which originates from angiotensinogen, produced by the liver. The formation of angiotensin I from angiotensinogen is rate-limited by the protease renin which is produced from the juxtaglomerular cells of the kidney.

Primary stimulation for renin secretion includes:

impaired renal perfusion,

salt depletion, and adrenergic stimulation.

Ang II inhibits renin secretion, via negative feedback loop. Although the majority of Ang I is converted to Ang II primarily through the activity of ACE, non-ACE pathways also exist and modulate the production of Ang II.

The highest concentration of ACE exists within the pulmonary circulation; however, many studies have documented the existence of local tissue RAAS.Ang II is involved with vascular tone and endothelial function, cardiac contractility, and impulse propagation, and stimulates the formation and secretion of aldosterone; it has pleiotropic effects on cellular growth and apoptosis.

Front 9

Regarding wernicke’s encepahalopathy

May be precipitated by a high protein diet

Vegetarianism is a common cause

B/L lateral rectus palsies may occur

Papilloedema is common

MRI may help in the diagnosis

Back 9

Signs and symptomsIn addition to the classical triad of symptoms—encephalopathy, ataxic gait, and oculomotor dysfunction—clinical signs of WE may include the following:Acute confusion/DeliriumAtaxiaOphthalmoplegiaMemory disturbanceHypothermia with hypotensionDelirium tremens

DiagnosisThe clinical diagnosis of WE in alcoholics requires two of the following four signs:

(i) dietary deficiencies

(ii) eye signs,

(iii) cerebellar dysfunction, and (iv) either an altered mental state or mild memory impairment. Although WE remains a clinical diagnosis with no characteristic abnormalities in diagnostic studies, the use of laboratory and radiographic tests remains important to exclude alternate or coexisting medical conditions.ManagementRapid correction of brain thiamine deficiency is the goal of therapy.

Administration of thiamine improves the patient’s condition to some degree in almost all cases; however, persistent neurologic dysfunction is common. Oral absorption is unreliable in patients at risk of Wernicke encephalopathy, which emphasizes the importance of parenteral treatment.

Although as little as 2 mg of thiamine may be enough to reverse symptoms, the dose of thiamine required to prevent or treat WE in most alcoholic patients may be as high as greater than 500 mg given once or, preferably, 2 or 3 times daily parenterally, intravenous is preferred to intramuscular administration.

EtiologyCausesThiamine deficiency is characteristically associated with chronic alcoholism, because it affects thiamine uptake and utilization. In long-term alcoholics, malnutrition can reduce intestinal thiamine absorption by 70%, decreasing serum levels of thiamine to between 30% and 98% below the lower level established for normal subjects. Thiamine acts as a coenzyme in the metabolism of glucose and lipids, and, as stores of water-soluble vitamins are limited in the body, deficiency can present within 2 to 3 weeks of cessation of intake.

Chronic alcohol consumption does not necessarily result in WE if dietary thiamine intake is adequate. It may induce thiamine deficiency through several potential mechanisms: genetic predisposition, replacement of vitamin-containing foods by the high calorific value of alcohol, impaired absorption of thiamine from the gut, impairment of storage by the liver, thiamine transport problems, other nutritional deficiencies, decreased phosphorylation to thiamine pyrophosphate and excessive requirements for the metabolism of alcohol.

WE may develop in nonalcoholic conditions, such as prolonged starvation, hyperemesis gravidarum, and bariatric surgery.

The numerous reports of severe thiamine deficiency after obesity surgery have led to the expression "bariatric beriberi.” Other causes of thiamine deficiency include total parenteral nutrition deficient in thiamine, formula deficient in thiamine, and hemodialysis-induced thiamine deficiency in patients with end-stage renal disease.Other uncommon etiologies of WE are:

forced or self-imposed starvation, protein-energy malnutrition resulting from inadequate diet or malabsorption (from celiac sprue), conditions associated with protracted vomiting (eg, hyperemesis gravidarum), carbohydrate loading in the presence of marginal thiamine stores (feeding after starvation), other gastric bypass surgeries, . A correlation between hemodialysis and WE has been demonstrated possibly secondary to inadvertent dialysis of the water-soluble thiamine combined with malnutrition in the end-stage renal disease population.

The most common inciting factor precipitating WE in the setting of thiamine deficiency is infection. Concomitant illnesses, such as pneumonia or even meningitis, do not exclude a co-diagnosis of WE.

Iatrogenic exacerbation of WE can occur with prolonged glucose or carbohydrate loading in the setting of thiamine deficiency.

However, a single, acute administration of glucose does not appear to cause this effect. Nutritionally deficient patients receiving glucose should also receive thiamine, but urgent administration of glucose should not be delayed pending thiamine administration.

Hint 9

Front 10

Subacute combined degeneration of the spinal cord

80% of pts with pernicious anaemia suffer from this neurological condition

Most pts have associated megaloblastic anaemia

excluded if the pt has a normal Hb level

Clinical features are caued by demyelination of posterior columns and spinothalamic tracts

Sphincters may get involved in later stages

Copper deficiency could present with similar clinical findings

Back 10

The neurologic features are attributable to pathology in the peripheral and optic nerves, posterior and lateral columns of the spinal cord (subacute combined degeneration), and in the brain.

Interestingly, hematologic and neurologic manifestations are occasionally dissociated.

An inverse correlation in the severity of both manifestations has been suggested. In patients with neuropsychiatric abnormalities, 28% lack anemia or macrocytosis.

Clinical manifestations due to vitamin B-12 deficiency are unrelated to etiology. In a prospective comparative study between antiparietal cell antibody positive and negative patients, no significant difference was shown in clinical, electrodiagnostic, and radiological features.

Although the clinical features of vitamin B-12 deficiency may consist of a classic triad of weakness, sore tongue, and paresthesias, these are not usually the chief symptoms.

Onset is subacute or gradual, although more acute courses have been described, in particular after N 2 O exposure.

Onset is often with a sensation of cold, numbness, or tightness in the tips of the toes and then in the fingertips, rarely with lancinating pains. Simultaneous involvement of arms and legs is uncommon, and onset in the arms is even rarer.

Paresthesias are ascending and occasionally involve the trunk, leading to a sensation of constriction in the abdomen and chest.

Untreated patients may develop limb weakness and ataxia.In 1991, Healton et al performed detailed neurologic evaluations of 143 patients with vitamin B-12 deficiency; 74% presented with neurologic symptoms. [19]Isolated numbness or paresthesias were present in 33%.Gait abnormalities occurred in 12%.Psychiatric or cognitive symptoms were noted in 3%.Visual symptoms were reported in 0.5%.

Symptoms include subacute progressive decrease in visual acuity, usually caused by bilateral optic neuropathy and rarely pseudotumor cerebri or optic neuritis.

Rare autonomic features include orthostasis, sexual dysfunction, and bowel and bladder incontinence.

Other symptoms include lightheadedness and impaired taste and smell.

Nonneurologic symptoms, some of which may also reflect autonomic nervous system involvement, were present in 26%.

Constitutional symptoms, including anorexia and weight loss occurred in 50%. Low-grade fever that resolves with treatment occurred in 33% of cases. Other symptoms include fatigue and malaise.

Cardiovascular symptoms include syncope, dyspnea, orthopnea, palpitations, and angina.

Gastrointestinal symptoms include heartburn, flatulence, constipation, diarrhea, sore tongue, and early satiety.PhysicalMost patients exhibit signs of peripheral nervous system (PNS) or spinal cord involvement, but the extent of PNS involvement remains unclear, in part because both neuropathy and myelopathy can cause impaired vibration sense, ataxia, and paresthesias. Either can be affected first in the early stages. Objective sensory abnormalities usually result from posterior column involvement and less often from PNS disease.Isolated neuropathy was reported in 25% of patients.Myelopathy occurred in 12% of cases.A combination of neuropathy and myelopathy was noted in 41%.

Neuropsychiatric manifestations, such as recent memory loss with reduced attention span and otherwise normal cognition, depression, hypomania, paranoid psychosis with auditory or visual hallucinations (megaloblastic madness), violent behavior, personality changes, blunted affect, and emotional liability, were reported in 8% of patients.

Ocular findings included a cecocentral scotoma and occurred in 0.5% of cases. Others have described optic atrophy, nystagmus, small reactive pupils, and chiasmatic lesion causing bitemporal hemianopia.

Early in the course, poor joint position and vibration sense predominate. Typically, the legs are affected before the arms. Rarely are all limbs affected simultaneously. A Romberg sign is commonly found. The gait may be wide based.

On presentation, 50% of patients have absent ankle reflexes with relative hyperreflexia at the knees. Plantars are initially flexor and later extensor. A Hoffman sign may be found.

As the disease progresses, ascending loss of pinprick, light touch, and temperature sensation occurs. Later, depending on the predominance of posterior column versus cortical spinal tract involvement, ataxia or spastic paraplegia predominates. Then, PNS involvement causes distal limb atrophy.

Cognitive testing may reveal mild impairment or frank dementia.

Nonneurologic manifestations include the following:General - Lemon-yellow waxy pallor, premature whitening of hair, flabby bulky frame, mild icterus, and blotchy skin pigmentation in dark-skinned patientsCardiovascular - Tachycardia, congestive heart failureGastrointestinal - Beefy, red, smooth, and sore tongue with loss of papillae that is more pronounced along edgesCausesInadequate vitamin B-12 absorption is the major pathomechanism and may result from several factors.Intrinsic factor deficiencyPA accounts for 75% of cases of vitamin B-12 deficiency.

It is an autoimmune attack on gastric IF. Antibodies are present in 70% of patients. They may block the formation of the cobalamin-IF complex or block its binding with cublin. Other antibodies are directed at parietal cell hydrogen-potassium adenosine triphosphatase (ATPase).Destruction of gastric mucosa can occur from gastrectomy or Helicobacter pylori infection. Deficient vitamin B-12 intake: Intake may be inadequate because of strict vegetarianism (rare), breastfeeding of infants by vegan mothers, alcoholism, or following dietary fads.Disorders of terminal ileum: Tropical sprue, celiac disease, enteritis, exudative enteropathy, intestinal resection, Whipple disease, ileal tuberculosis,Competition for cobalamin: Competition for cobalamin may occur in blind loop syndrome or with fish tapeworm (Diphyllobothrium latum).Abnormalities related to protein digestion related to achlorhydria: Abnormalities include atrophic gastritis, pancreatic deficiency, proton pump inhibitor use, and Zollinger-Ellison syndrome, in which the acidic pH of the distal small intestine does not allow the cobalamin-IF complex to bind with cublin.Medications: Medications include colchicine, neomycin, and p -aminosalicylic acid.

In AIDS, vitamin B-12 deficiency is not infrequent. Although the exact etiology remains obscure, it is likely a multimodal process involving poor nutrition, chronic diarrhea, ileal dysfunction, and exudative enteropathy. Low vitamin B-12 levels may be more common in late than in early HIV disease.

Hint 10

Front 11

Pernicious anemia

Back 11

The onset of pernicious anemia usually is insidious and vague. The classic triad of weakness, sore tongue, and paresthesias may be elicited but usually is not the chief symptom complex. Typically, medical attention is sought because of symptoms suggestive of cardiac, renal, genitourinary, gastrointestinal, infectious, mental, or neurological disorders, and the patient is found to be anemic with macrocytic cellular indices.

General symptoms

Weight loss of 10-15 lb occurs in about 50% of patients and probably is due to anorexia, which is observed in most patients.

Low-grade fever occurs in one third of newly diagnosed patients and promptly disappears with treatment.

Cardiac symptoms

The anemia often is well tolerated in pernicious anemia, and many patients are ambulatory with hematocrit levels in the mid-teens. However, the cardiac output is usually increased with hematocrits less than 20%, and the heart rate accelerates.

Congestive heart failure and coronary insufficiency can occur, most particularly in patients with preexisting heart disease.

Gastrointestinal symptoms

Approximately 50% of patients have a smooth tongue with loss of papillae. This is usually most marked along the edges of the tongue. The tongue may be painful and beefy red. Occasionally, red patches are observed on the edges of the dorsum of the tongue. Patients may report burning or soreness, most particularly on the anterior third of the tongue. These symptoms may be associated with changes in taste and loss of appetite.

Patients may report either constipation or having several semisolid bowel movements daily. These symptoms have been attributed to megaloblastic changes of the cells of the intestinal mucosa.

Nonspecific gastrointestinal (GI) symptoms are not unusual and include anorexia, nausea, vomiting, heartburn, pyrosis, flatulence, and a sense of fullness.

Rarely, patients present with severe abdominal pain associated with abdominal rigidity; this has been attributed to spinal cord pathology. Venkatesh and colleagues report the case of a patient who presented with epigastric pain, diarrhea, and vomiting and was found to have thrombosis of the portal, superior mesenteric, and splenic veins due to hyperhomocysteinemia secondary to pernicious anemia.

Neurologic symptoms

Neurologic symptoms can be elicited in patients with pernicious anemia. The most common of these are paresthesias, weakness, clumsiness, and an unsteady gait.

The last two symptoms become worse in darkness because they reflect the loss of proprioception in a patient who is unable to rely upon vision for compensation.

These neurologic symptoms are due to myelin degeneration and loss of nerve fibers in the dorsal and lateral columns of the spinal cord and cerebral cortex.

Neurologic symptoms and findings may be present in the absence of anemia. This is more common in patients taking folic acid or on a high-folate diet.

Older patients may present with symptoms suggesting senile dementia or Alzheimer disease; memory loss, irritability, and personality changes are commonplace.

Megaloblastic madness is less common and can be manifested by delusions, hallucinations, outbursts, and paranoid schizophrenic ideation. Identifying the cause is important because significant reversal of these symptoms and findings can occur with vitamin B12 administration.

While neurologic symptoms usually occur in the elderly, they can rarely occur in the young.

Genitourinary symptoms

Urinary retention and impaired micturition may occur because of spinal cord damage.

This can predispose patients to urinary tract infections.

Symptoms of thrombotic complicationsA study of four patients revealed that pernicious anemia can lead to hyperhomocysteinemia that is significant enough to lead to venous thrombosis, even in the absence of any other risk factors for thromboembolism.

Front 12

Sleep

Hypersomnolence is the most common sleep disorder

Most of adult sleep is in REM

Normal person has about 10 sleep cycles every night

Dreaming occurs in REM

Sleep walking occurs in NREM

Back 12

Q

Front 13

Tremor

Parkinsonian tremor is the most disabling type of tremor

Action tremor is typically seen in essential tremor

Intention tremor is seen in cerebellar disease

Betablockers are very effective in controlling intention tremor

Orthostatic tremor responds to clonazepam

Back 13

Tremors are involuntary, rhythmic, oscillatory movements of reciprocal, antagonistic muscle groups, typically involving the hands, head, face, vocal cords, trunk, or legs.

Diagnosis is clinical. Treatment depends on the cause and type of tremor and may involve avoidance of triggers (physiologic),

propranolol or primidone (essential),

physical therapy (cerebellar),

levodopa (parkinsonian), and

possibly deep brain stimulation or thalamotomy (disabling and drug-refractory).

Tremor may be Normal (physiologic)

Pathologic

Physiologic tremor, usually barely perceptible, becomes noticeable in many people during physical or mental stress.

Tremors vary in

.Pattern of occurrence (eg, intermittent, constant)

.Severity

.Acuity (eg, gradual, abrupt)

The severity of tremor may not be related to the seriousness of the underlying disorder. 👽

For example, essential tremor is generally thought of as benign and should not shorten life, but symptoms can be disabling, and cerebellar degeneration has been detected in some neuropathologic studies.

Pathophysiology

Various lesions in the

brain stem,

extrapyramidal system, or

cerebellum can cause tremors.

Neural dysfunction or lesions that cause tremor may result from injury, ischemia, metabolic abnormalities, or a neurodegenerative disorder.

Sometimes tremor is a familial condition (eg, essential tremor).

ClassificationTremor is classified primarily based on when it occurs:

Resting tremors are visible at rest and occur when a body part is completely supported against gravity. Resting tremors are minimal or absent during activity. They occur at a frequency of 3 to 6 cycles/sec (Hz).

Action tremors are maximal when a body part is moved voluntarily. Action tremors may or may not change in severity as a target is reached; they can occur at very different frequencies, but the frequency is always < 13 Hz.Action tremors include kinetic, intention, and postural tremors.

👚 Kinetic tremors appear in the last part of a movement toward a target; amplitude is low.

🙊🙌 Intention tremors occur during voluntary movement toward a target, but amplitude is high and frequency is low during the complete movement, while the tremor worsens as the target is reached (as seen in finger-to-nose testing);

they occur at a frequency of 3 to 10 Hz.

🚶Postural tremors are maximal when a limb is maintained in a fixed position against gravity (eg, holding the arms stretched out); they occur at a frequency of 5 to 8 Hz. Sometimes they are modified by specific positions or tasks, which may indicate their origin; for example, dystonia may trigger a tremor (dystonic tremor).

Complex tremors can have components of more than one type of tremor.Tremor can also be classified based on whether it is

Physiologic (within the range of normal)

A primary disorder (essential tremor, Parkinson disease)

Secondary to a disorder (eg, stroke)

Tremor is usually described based on frequency of oscillations (rapid or slow) and amplitude of movement (fine or coarse).

👐🙌

Physiologic tremor

Physiologic tremor occurs in otherwise healthy people. It is an action or postural tremor that tends to affect both hands about equally; amplitude is usually fine. It is often noticeable only when certain stressors are present.

These stressors include

Anxiety-Fatigue-Exercise-Sleep deprivation-Withdrawal of alcohol or certain other CNS depressant drugs (eg, benzodiazepines, opioids)-Certain disorders (eg, hyperthyroidism), when symptomatic-Consumption of caffeine or recreational drugs such as cocaine, amphetamines, or phencyclidine

Use of certain therapeutic drugs, such as theophylline, beta-adrenergic agonists, corticosteroids, and valproate

Pathologic (nonphysiologic) tremor

There are many causes but the most common are

For action or postural tremors: Essential tremor

For resting tremors: Parkinson disease

For intention tremors: Cerebellar dysfunction (eg, due to a stroke, trauma, or multiple sclerosis)

Some Causes of Tremor causing Drugs can cause or aggravate different types of tremor. Low doses of some sedatives (eg, alcohol) may relieve some tremors (eg, essential and physiologic tremor); higher doses may cause or exacerbate tremor.

Hint 13

Tremor can be classified as resting or action (which includes intention, kinetic, and postural tremors).

The most common causes of tremor include physiologic tremor, essential tremor, and Parkinson disease.

History and physical examination can typically identify the etiology of tremor.

Consider Parkinson disease if patients have a resting tremor, consider essential or physiologic tremor if they have a postural or an action tremor, and consider cerebellar tremor if they have an intention tremor.

If tremor begins abruptly or occurs in patients who are < 50 and do not have a family history of benign tremor, evaluate them promptly and thoroughly.

Treat according to the cause and type of tremor: avoidance of triggers (physiologic), propranolol or primidone (essential), physical therapy (cerebellar), usually levodopa (parkinsonian), and possibly deep brain stimulation (disabling and drug-refractory)

Front 14

MSA

Those with early autonomic dysfunction have a worse prognosis

Diagnosis is made clinically

MRI is helpful in the evaluation

Humming bird sign is seen in MRI

Anal sphincter

EMG may show denervation changes

Back 14

Multiple system atrophy is a relentlessly progressive neurodegenerative disorder causing pyramidal, cerebellar, and autonomic dysfunction.

It includes 3 disorders previously thought to be distinct: olivopontocerebellar atrophy, striatonigral degeneration, and Shy-Drager syndrome.

Symptoms include hypotension, urinary retention, constipation, ataxia, rigidity, and postural instability.

Diagnosis is clinical. Treatment is symptomatic, with volume expansion, compression garments, and vasoconstrictor drugs.

Multiple system atrophy affects about twice as many men as women.

Mean age at onset is about 53 yr; after symptoms appear, patients live about 9 to 10 yr.

There are 2 types of multiple system atrophy (MSA); types are based on the initial symptoms that predominate:

MSA-C: Characterized by ataxia and postural instability (cerebellar dysfunction)

MSA-P: Similar to Parkinson disease but often without tremor and often unresponsive to levodopa (parkinsonian symptoms)Both types involve autonomic nervous system dysfunction.

Although multiple system atrophy begins as one type, symptoms of the other type eventually develop. After about 5 yr, symptoms tend to be similar regardless of which disorder developed first.

Front 15

Etiology of multiple system atrophy is unknown, but neuronal degeneration occurs in several areas of the brain; the area and amount damaged determine initial symptoms.

A characteristic finding is cytoplasmic inclusion bodies containing alpha-synuclein within oligodendroglial cells.

Multiple system atrophy is a synucleinopathy (due to synuclein deposition); synuclein can also accumulate in patients with Parkinson disease, pure autonomic failure, or Lewy body dementia.

Synuclein is a neuronal and glial cell protein that can aggregate into insoluble fibrils and form Lewy bodies.

Back 15

Initial symptoms of multiple system atrophy vary but include a combination of

Parkinsonism unresponsive to levodopa

Cerebellar abnormalities

Symptoms due to autonomic insufficiency

Parkinsonian symptoms

Parkinsonian symptoms predominate in striatonigral degeneration. They include rigidity, bradykinesia, postural instability, and jerky postural tremor.

High-pitched, quavering dysarthria is common.

In contrast to Parkinson disease, multiple system atrophy usually does not usually cause resting tremor and dyskinesia, and symptoms respond poorly and transiently to levodopa.

Cerebellar abnormalities

Cerebellar abnormalities predominate in olivopontocerebellar atrophy. They include ataxia, dysmetria, dysdiadochokinesia (difficulty performing rapidly alternating movements), poor coordination, and abnormal eye movements.

Autonomic symptoms

Typically, autonomic insufficiency causes orthostatic hypotension (symptomatic fall in BP when a person stands, often with syncope), urinary retention, urinary incontinence, constipation, and erectile dysfunction.

Other autonomic symptoms, which may occur early or late, include decreased sweating, difficulty breathing and swallowing, fecal incontinence, and decreased tearing and salivation.

Rapid eye movement (REM) sleep behavior disorder (eg, speech or skeletal muscle movement during REM sleep), respiratory stridor, and sleep apnea are common. Patients are often unaware of REM sleep behavior disorder.Patients may have nocturnal polyuria; contributing factors may include a circadian decrease in arginine vasopressin and treatments used to increase blood volume

Front 16

Diagnosis -Clinical evaluation (parkinsonism or cerebellar symptoms that respond poorly to levodopa plus autonomic insufficiency)

MRI

Autonomic tests

Diagnosis of multiple system atrophy is suspected clinically, based on the combination of autonomic insufficiency and parkinsonism or cerebellar symptoms.

Similar symptoms may result from Parkinson disease, Lewy body dementia, pure autonomic failure, autonomic neuropathies, progressive supranuclear palsy, multiple cerebral infarcts, or drug-induced parkinsonism.

No diagnostic test is definitive, but some (eg, MRI, nuclear imaging with 123I-metaiodobenzylguanidine [MIBG], autonomic tests) help confirm clinical suspicion of multiple system atrophy—for example, if MRI shows characteristic changes in the midbrain, pons, or cerebellum.

MIBG scans show intact innervation of the heart.Autonomic tests indicate generalized autonomic failure.

Back 16

Orthostatic hypotension: Treatment includes intravascular volume expansion with salt and water supplementation and sometimes fludrocortisone 0.1 to 0.4 mg po once/day.

👢 Use of compression garments for the lower body (eg, abdominal binder, compression stockings) and alpha-adrenoreceptor stimulation with midodrine 10 mg po tid may help.

However, midodrine also increases peripheral vascular resistance and supine BP, which may be problematic.

Raising the head of the bed about 10 cm reduces nocturnal polyuria and supine hypertension and may reduce morning orthostatic hypotension. Alternatively, droxidopa may be used; its action is similar to that of midodrine, but duration of action is longer

.Parkinsonism: Levodopa/carbidopa 25/100 mg po at bedtime may be tried to relieve rigidity and other parkinsonian symptoms, but this combination is usually ineffective or provides modest benefit.

Urinary incontinence: If the cause is detrusor hyperreflexia, oxybutynin chloride 5 mg po tid or tolterodine 2 mg po bid may be used.

Tamsulosin 0.4 to 0.8 mg once/day may be effective for urinary urgency.

Alternatively, the beta-3 adrenergic agonist mirabegron 25 to 50 mg once/day can be used; unlike tamsulosin, mirabegron does not worsen orthostatic hypotension.

Urinary retention: Many patients must self-catheterize their bladder.

Constipation: A high-fiber diet and stool softeners can be used; for refractory cases, enemas may be necessary.

Erectile dysfunction: Drugs such as sildenafil 50 mg po prn or tadalafil 2.5 to 5 mg once/day and various physical means can be used.

Patients require supportive therapy because the disorder is progressive and fatal.

Front 17

Key points

Back 17

Multiple system atrophy can include parkinsonian symptoms, cerebellar abnormalities, and autonomic insufficiency in various degrees of severity.

Diagnose this disorder based on clinical, autonomic, and MRI findings, but consider Parkinson disease, Lewy body dementia, pure autonomic failure, autonomic neuropathies, progressive supranuclear palsy, multiple cerebral infarcts, and drug-induced parkinsonism, which can all cause similar symptoms.

Use treatments specific for the symptoms present

Front 18

Q

78.Parkinson’s disease

Bradykinesia is a typical feature

Has a better prognosis than MSA

Hearing impairment may preceed motor symptoms

Sense of smell is often affected in PD

Early memory impairment suggests alternative diagnosis

Back 18

Parkinson disease is a slowly progressive, degenerative disorder characterized by resting tremor, stiffness (rigidity), slow and decreased movement (bradykinesia), and gait and/or postural instability.

Diagnosis is clinical.

Treatment aims to restore dopaminergic function in the brain with levodopa plus carbidopa and/or other drugs (eg, dopamine agonists, MAO type B [MAO-B] inhibitors, amantadine).

For refractory, disabling symptoms in patients without dementia, stereotactic deep brain stimulation or lesional surgery and levodopa and an apomorphine pump may help.

Hint 18

Parkinson disease is a synucleinopathy and thus can overlap with other synucleinopathies (eg, dementia with Lewy bodies, multiple system atrophy).Suspect Parkinson disease based on characteristic features: resting tremor, muscle rigidity, slow and decreased movement, and postural and gait instability.Distinguish Parkinson disease from disorders that cause similar symptoms based mainly on the history and physical examination results, but also test responsiveness to levodopa; sometimes neuroimaging is useful.Typically, use levodopa/carbidopa (the mainstay of treatment), but other drugs (amantadine, dopamine agonists, MAO-B inhibitors, COMT inhibitors) may be used before and/or with levodopa/carbidopa.Consider surgical procedures, such as deep brain stimulation, if patients have symptoms refractory to optimal drug therapy and do not have cognitive impairment or a psychiatric disorder.

Front 19

Q

CI for thrombolysis include

Current aspirin use

Being on warfarin

A minor stroke 1 month before

Age over 80yrs

Demonstrable clot occluding the ICA

Back 19

The principal clinical syndromes that result are as follows:Acute myocardial infarction (AMI)Deep vein thrombosis (DVT)Pulmonary embolism (PE)Acute ischemic stroke (AIS)Acute peripheral arterial occlusionOcclusion of indwelling catheters

Pathologic thrombosis can occur in any vessel at any location in the body. There are several conditions that predispose to thrombosis, including the following:Atherosclerosis (plaque rupture)Blood flow changesMetabolic disorders (diabetes mellitus and hyperlipidemia)Hypercoagulable statesSmokingTrauma and burns

Front 20

Thrombolytic Therapy for Acute Myocardial Infarction

Average age at first MI is 64.9 years for men and 72.3 years for women.Thrombolytic therapy is indicated in patients with evidence of ST-segment elevation MI (STEMI) or presumably new left bundle-branch block (LBBB) presenting within 12 hours of the onset of symptoms if there are no contraindications to fibrinolysis.

STEMI is defined as new ST elevation at the J point in at least two contiguous leads of 2 mm (0.2 mV) or more in men or 1.5 mm (0.15 mV) in women in leads V2-V3 and/or 1 mm (0.1 mV) or more in other contiguous limb leads.

STEMI equivalents, such as isolated posterior-wall MI, present with ST depression in two or more precordial leads (V1-V4).

In left main coronary artery occlusion, Electrocardiography (ECG) reveals multilead ST depression in at least six leads with coexistent ST elevation in lead aVR.

New or presumably new LBBB at presentation occurs infrequently and should not be considered diagnostic of acute MI (AMI) in isolation unless it is clinically unstable.

The Sgarbossa criteria are the most validated tool to aid in the diagnosis of STEMI in the presence of LBBB

Coronary atherosclerosis is a diffuse process characterized by segmental lesions called coronary plaques. The plaque ruptures, exposing the endothelial lining and allowing prothrombotic enzymes and molecular triggers to mix with the blood. Platelets are activated, and the coagulation cascade is amplified, resulting in a thrombus that occludes the vessel and prevents the circulation of oxygenated blood. Irreversible ischemia-induced myocardial necrosis may occur within 20-60 minutes of occlusion.Patients with STEMI usually have complete occlusion of an epicardial coronary vessel caused by an acute thrombotic obstruction.

The earlier the patient presents, and the earlier the artery can be recanalized, the better.

The mainstay of treatment is reperfusion therapy involving either administration of fibrinolytics (pharmacologic reperfusion) or primary percutaneous coronary intervention (PCI; ie, mechanical reperfusion).

PCI performed within 90 minutes of a patient's arrival is superior to fibrinolysis with respect to combined endpoints of death, stroke, and reinfarction.

Unfortunately, PCI is not widely available at acute care hospitals:

Although primary PCI is the preferred therapy for STEMI, it has severe logistic restraints: Treatment is delayed by patient transport, emergency department (ED) delay, and preparation of the catheterization laboratory. Researchers noted that any mortality benefit of primary PCI compared with onsite fibrinolysis was nullified when the time delay to primary PCI was 120 minutes or more

2013 STEMI Focused Update, the writing committee recommended fibrinolytic therapy when there was an anticipated delay to performing primary PCI within 120 minutes of first medical contact (FMC). FMC was defined as the time at which the EMS provider arrives at the patient’s side. [16]The benefits of fibrinolytic therapy are well established during the initial 12 hours after symptom onset. Guidelines mention that administration of a fibrinolytic agent should be considered in symptomatic patients presenting more than 12-24 hours after symptom onset with STEMI affecting a large area of myocardium or hemodynamic instability if PCI is not available.

The current guideline recommends that patients arriving to a non-PCI hospital should immediately receive fibrinolysis and then be transferred to a PCI-capable center where angiography and PCI should be performed.

Management of patients after early fibrinolysis has been the subject of several studies. The TRANSFER-AMI [23] and CARESS-in-AMI [24] trials suggested that transfer of patients to a PCI-capable hospital within 6 hours after fibrinolysis was associated with significantly fewer ischemic complications than transfer after 24 hours.Lack of resolution of ST elevation by at least 50% in the worst lead at 90 minutes should prompt strong consideration of a decision to proceed with immediate coronary angiography and rescue PCI. The 2013 guidelines recommended transfer for angiography after fibrinolytic therapy for cardiogenic shock or severe acute heart failure irrespective of time delay from MI onset; failed reperfusion or reocclusion, and as part of an invasive strategy in stable patients with PCI between 3 and 24 hours after successful fibrinolysis. [16]Fibrinolytic therapy is a proven treatment for the management of AMI. It is more universally available to patients without contraindications, can be administered by any properly trained health care provider, and can be given in the prehospital setting. Its efficacy declines as the duration of ischemia increases. The goal is a door-to-needle time of less than 30 minutes, and every effort must be made to minimize the time to therapy. Patients older than 75 years derive significant benefit from fibrinolytic therapy, even though their risk of bleeding is higher.Fibrinolytic agents are given in conjunction with antithrombin and antiplatelet agents, which help to maintain vessel patency once the clot has been dissolved.Aspirin inhibits platelets; the recommended dose is 162-325 mg of chewable aspirin.Clopidogrel also inhibits platelets. For patients aged 75 years or younger, administer an oral loading dose of 300 mg. The COMMIT-CCS-2 and CLARITY-TIMI 28 trials provided evidence for benefit of adding clopidogrel to aspirin in patients undergoing fibrinolytic therapy. [25, 26] In patients older than 75 years, no loading dose is required; administer 75 mg orally. [16]Heparin (unfractionated heparin [UFH] or low-molecular-weight heparin [LMWH]) inhibits thrombin. For UFH, the recommended dose is an intravenous (IV) bolus of 60 U/kg (maximum, 4000 U) followed by an initial infusion of 12 U/kg/hr (maximum, 1000 U/hr) adjusted to maintain the activated partial thromboplastin time (aPTT) at 1.5-2 times the control value.LMWH (eg, enoxaparin) is emerging as an alternative to UFH. Enoxaparin may be administered to patients younger than 75 years; the recommendation is a 30 mg IV bolus followed by 1 mg/kg subcutaneously every 12 hours. For patients aged 75 years or older, the IV bolus is eliminated and the subcutaneous dose reduced to 0.75 mg/kg every 12 hours. Regardless of age, if the creatinine clearance is less than 30 mL/min, the subcutaneous dose is 1 mg/kg every 24 hours. [16] Enoxaparin appeared superior to UFH in the EXTRACT-TIMI 25 trial. [27]Fondaparinux should not be given as the sole anticoagulant to patients referred for PCI and is contraindicated for patients with a creatitine clearance of less than 30 mL/min

Back 20

Absolute contraindications for fibrinolytic use in STEMI include the following:

Prior intracranial hemorrhage (ICH)Known structural cerebral vascular lesion Known malignant intracranial neoplasm

Ischemic stroke within 3 months

Suspected aortic dissection

Active bleeding or bleeding diathesis (excluding menses)

Significant closed head trauma or facial trauma within 3 months

Intracranial or intraspinal surgery within 2 months

Severe uncontrolled hypertension (unresponsive to emergency therapy)

For streptokinase, prior treatment within the previous 6 months

Relative contraindications for fibrinolytic use in STEMI include the following:

History of chronic, severe, poorly controlled hypertension

Significant hypertension on presentation (systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg

Traumatic or prolonged (>10 minutes) cardiopulmonary resuscitation (CPR) or major surgery less than 3 weeks previously

History of prior ischemic stroke not within the last 3 months

Dementia

Recent (within 2-4 weeks) internal bleeding

Noncompressible vascular punctures

Pregnancy

Active peptic ulcer

Current use of an anticoagulant (eg, warfarin sodium) that has produced an elevated international normalized ratio (INR) higher than 1.7 or a prothrombin time (PT) longer than 15 seconds

Front 21

Q

TIA

To diagnose according to the new criteria a brain scan is required

TIA with transient weakness is more likely to lead a disabling stroke than a TIA causing amaurosis fugax 👿

Early investigation is the key to preventing a stroke

CHAD score helps prognosticate TIAs

If a pt with TIA has 99% occlusion of the corresponding ICA he should be heparinised

Back 21

Transient ischemic attack is focal brain ischemia that causes sudden, transient neurologic deficits and is not accompanied by permanent brain infarction (eg, negative results on diffusion-weighted MRI). Diagnosis is clinical. Carotid endarterectomy or stenting, antiplatelet drugs, and anticoagulants decrease risk of stroke after certain types of TIA

TIA is similar to ischemic stroke except that symptoms usually last < 1 h; most TIAs last < 5 min.

Infarction is very unlikely if deficits resolve within 1 h.

As shown by diffusion-weighted MRI and other studies, deficits that resolve spontaneously within 1 to 24 h are often accompanied by infarction and are thus no longer considered TIAs.

TIAs are most common among the middle-aged and elderly. TIAs markedly increase risk of stroke, beginning in the first 24 h.

Hint 21

Risk factors for TIA are the same as those for ischemic stroke. Modifiable risk factors include the following

:Alcoholism

Hypertension

Cigarette smoking

Dyslipidemia

Diabetes

Insulin resistance

(1)Obesity

Lack of physical activityHigh-risk diet (eg, high in saturated fats, trans fats, and calories)Psychosocial stress (eg, depression)Heart disorders (particularly disorders that predispose to emboli, such as acute MI, infective endocarditis, and atrial fibrillation)Use of certain drugs (eg, cocaine, amphetamines)Hypercoagulability

Vasculitis

Unmodifiable risk factors include the following:Prior strokeOlder ageFamily history of strokeMale sexMost TIAs are caused by emboli, usually from carotid or vertebral arteries, although most of the causes of ischemic stroke can also result in TIAs.Uncommonly, TIAs result from impaired perfusion due to severe hypoxemia, reduced oxygen-carrying capacity of blood (eg, profound anemia, carbon monoxide poisoning), or increased blood viscosity (eg, severe polycythemia), particularly in brain arteries with preexisting stenosis. Systemic hypotension does not usually cause cerebral ischemia unless it is severe or arterial stenosis preexists because autoregulation maintains brain blood flow at near-normal levels over a wide range of systemic BPs.In subclavian steal syndrome, a subclavian artery stenosed proximal to the origin of the vertebral artery “steals” blood from the vertebral artery (in which blood flow reverses) to supply the arm during exertion, causing signs of vertebrobasilar ischemia.

Front 22

mptoms and SignsNeurologic deficits are similar to those of strokes (see Table: Selected Stroke Syndromes). Transient monocular blindness (amaurosis fugax), which usually lasts < 5 min, may occur when the ophthalmic artery is affected.TABLESelected Stroke Syndromes iconSymptoms of TIAs begin suddenly, usually last 2 to 30 min, then resolve completely. Patients may have several TIAs daily or only 2 or 3 over several years. Symptoms are usually similar in successive carotid attacks but vary somewhat in successive vertebrobasilar attacks.

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Resolution of stroke-like symptoms within 1 hNeuroimagingEvaluation to identify the causeTransient ischemic attacks are diagnosed retrospectively when sudden neurologic deficits referable to ischemia in an arterial territory resolve within 1 h.Isolated peripheral facial nerve palsy, loss of consciousness, or impaired consciousness does not suggest TIA. TIAs must be distinguished from other causes of similar symptoms, such asHypoglycemiaMigraine auraPostictal [Todd] paralysis (a transient neurologic deficit, usually weakness, of the limb contralateral to the seizure focus)Because an infarct, a small hemorrhage, and even a mass lesion cannot be excluded clinically, neuroimaging is required. Usually, CT is the study most likely to be immediately available. However, CT may not identify infarcts for > 24 h. MRI usually detects evolving infarction within hours. Diffusion-weighted MRI is the most accurate imaging test to rule out an infarct in patients with presumed TIA but is not always available.The cause of a TIA is sought as for causes of ischemic strokes; evaluation includes tests for carotid stenosis, cardiac sources of emboli, atrial fibrillation, and hematologic abnormalities and screening for stroke risk factors. Because risk of subsequent ischemic stroke is high and immediate, evaluation proceeds rapidly, usually on an inpatient basis. It is not clear which patients, if any, can be safely discharged from the emergency department. Risk of stroke after TIA or minor stroke is highest within the first 24 to 48 h, so if either is suspected, patients are typically admitted to the hospital for telemetry and evaluation.

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atmentPrevention of strokesTreatment of transient ischemic attacks is aimed at preventing strokes; antiplatelet drugs and statins are used. Carotid endarterectomy or arterial angioplasty plus stenting can be useful for some patients, particularly those who have no neurologic deficits but who are at high risk of stroke. Anticoagulation is indicated if cardiac sources of emboli are present.Modifying stroke risk factors, when possible, may prevent stroke.

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ointsA focal neurologic deficit that resolves within 1 h is almost always a transient ischemic attack.Test as for ischemic stroke.Use the same treatments used for secondary prevention of ischemic stroke (eg, antiplatelet drugs, statins, sometimes carotid endarterectomy or arterial angioplasty plus stenting).Drugs Mentioned In This Art

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Q

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75. Ischaemic strokeCan be reliably diagnosed at the bedside by a neurologist Surgery may be indicated in some pts with ischaemic strokeEarly administration of aspirin minimizes the cerebral damage due to the incident strokeHeparin should be considered in pts with progressive symptomsDexamethasone is standard care for large infarcts with progressive symptoms

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hemic stroke is sudden neurologic deficits that result from focal cerebral ischemia associated with permanent brain infarction (eg, positive results on diffusion-weighted MRI). Common causes are (from most to least common) atherothrombotic occlusion of large arteries; cerebral embolism (embolic infarction); nonthrombotic occlusion of small, deep cerebral arteries (lacunar infarction); and proximal arterial stenosis with hypotension that decreases cerebral blood flow in arterial watershed zones (hemodynamic stroke). Diagnosis is clinical, but CT or MRI is done to exclude hemorrhage and confirm the presence and extent of stroke. Thrombolytic therapy may be useful acutely in certain patients. Depending on the cause of stroke, carotid endarterectomy or stenting, antiplatelet drugs, or warfarin may help reduce risk of subsequent strokes.

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ologyThe following are the modifiable risk factors that contribute the most to increased risk of ischemic stroke:HypertensionCigarette smokingDyslipidemiaDiabetesInsulin resistance (1)Abdominal obesityAlcoholismLack of physical activityHigh-risk diet (eg, high in saturated fats, trans fats, and calories)Psychosocial stress (eg, depression)Heart disorders (particularly disorders that predispose to emboli, such as acute MI, infective endocarditis, and atrial fibrillation)Use of certain drugs (eg, cocaine, amphetamines)HypercoagulabilityVasculitisUnmodifiable risk factors include the following:Prior strokeOlder ageFamily history of strokeIschemia usually results from thrombi or emboli. Even infarcts classified as lacunar based on clinical criteria (morphology, size, and location) often involve small thrombi or emboli.ThrombosisAtherothrombotic occlusion of large arteries (thrombus superimposed on an atherosclerotic artery) is the most common cause of ischemic stroke.Atheromas, particularly if ulcerated, predispose to thrombi. Atheromas can occur in any major cerebral artery and are common at areas of turbulent flow, particularly at the carotid bifurcation. Partial or complete thrombotic occlusion occurs most often at the main trunk of the middle cerebral artery and its branches but is also common in the large arteries at the base of the brain, in deep perforating arteries, and in small cortical branches. The basilar artery and the segment of the internal carotid artery between the cavernous sinus and supraclinoid process are often occluded.Less common causes of thrombosis include vascular inflammation secondary to disorders such as acute or chronic meningitis, vasculitic disorders, and syphilis; dissection of intracranial arteries or the aorta; hypercoagulability disorders (eg, antiphospholipid syndrome, hyperhomocysteinemia); hyperviscosity disorders (eg, polycythemia, thrombocytosis, hemoglobinopathies, plasma cell disorders); and rare disorders (eg, fibromuscular dysplasia, moyamoya disease, Binswanger disease). Older oral contraceptive formulations increase risk of thrombosis. In children, sickle cell disease is a common cause of ischemic stroke.EmbolismEmboli may lodge anywhere in the cerebral arterial tree.Emboli may originate as cardiac thrombi, especially in the following conditions:Atrial fibrillationRheumatic heart disease (usually mitral stenosis)Post-MIVegetations on heart valves in bacterial or marantic endocarditisProsthetic heart valvesMechanical circulatory assist devices (eg, left ventricular assist device, or LVAD [2])Other sources include clots that form after open-heart surgery and atheromas in neck arteries or in the aortic arch. Rarely, emboli consist of fat (from fractured long bones), air (in decompression sickness), or venous clots that pass from the right to the left side of the heart through a patent foramen ovale with shunt (paradoxical emboli). Emboli may dislodge spontaneously or after invasive cardiovascular procedures (eg, catheterization). Rarely, thrombosis of the subclavian artery results in embolic stroke in the vertebral artery or its branches.Lacunar infarctsIschemic stroke can also result from lacunar infarcts. These small (≤ 1.5 cm) infarcts result from nonatherothrombotic obstruction of small, perforating arteries that supply deep cortical structures; the usual cause is lipohyalinosis (degeneration of the media of small arteries and replacement by lipids and collagen). Whether emboli cause lacunar infarcts is controversial.Lacunar infarcts tend to occur in elderly patients with diabetes or poorly controlled hypertension.Other causesAny factor that impairs systemic perfusion (eg, carbon monoxide toxicity, severe anemia or hypoxia, polycythemia, hypotension) increases risk of all types of ischemic strokes. A stroke may occur along the borders between territories of arteries (watershed areas); in such areas, blood supply is normally low, particularly if patients have hypotension and/or if major cerebral arteries are stenotic.Less commonly, ischemic stroke results from vasospasm (eg, during migraine, after subarachnoid hemorrhage, after use of sympathomimetic drugs such as cocaine or amphetamines) or venous sinus thrombosis (eg, during intracranial infection, postoperatively, peripartum, secondary to a hypercoagulability disorder).

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hophysiologyInadequate blood flow in a single brain artery can often be compensated for by an efficient collateral system, particularly between the carotid and vertebral arteries via anastomoses at the circle of Willis and, to a lesser extent, between major arteries supplying the cerebral hemispheres. However, normal variations in the circle of Willis and in the caliber of various collateral vessels, atherosclerosis, and other acquired arterial lesions can interfere with collateral flow, increasing the chance that blockage of one artery will cause brain ischemia.Some neurons die when perfusion is < 5% of normal for > 5 min; however, the extent of damage depends on the severity of ischemia. If it is mild, damage proceeds slowly; thus, even if perfusion is 40% of normal, 3 to 6 h may elapse before brain tissue is completely lost. However, if severe ischemia persists > 15 to 30 min, all of the affected tissue dies (infarction). Damage occurs more rapidly during hyperthermia and more slowly during hypothermia. If tissues are ischemic but not yet irreversibly damaged, promptly restoring blood flow may reduce or reverse injury. For example, intervention may be able to salvage the moderately ischemic areas (penumbras) that often surround areas of severe ischemia (these areas exist because of collateral flow).Mechanisms of ischemic injury includeEdemaMicrovascular thrombosisProgrammed cell death (apoptosis)Infarction with cell necrosisInflammatory mediators (eg, IL-1B, tumor necrosis factor-alpha) contribute to edema and microvascular thrombosis. Edema, if severe or extensive, can increase intracranial pressure.Many factors may contribute to necrotic cell death; they include loss of ATP stores, loss of ionic homeostasis (including intracellular calcium accumulation), lipid peroxidative damage to cell membranes by free radicals (an iron-mediated process), excitatory neurotoxins (eg, glutamate), and intracellular acidosis due to accumulation of lactate.

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Symptoms and signs of ischemic stroke depend on the part of brain affected. Patterns of neurologic deficits often suggest the affected artery (see Table: Selected Stroke Syndromes), but correlation is often inexact.TABLESelected Stroke SyndromesiconDeficits may become maximal within several minutes of onset, typically in embolic stroke. Less often, deficits evolve slowly, usually over 24 to 48 h (called evolving stroke or stroke in evolution), typically in atherothrombotic stroke. In most evolving strokes, unilateral neurologic dysfunction (often beginning in one arm, then spreading ipsilaterally) extends without causing headache, pain, or fever. Progression is usually stepwise, interrupted by periods of stability. A stroke is considered submaximal when after it is complete, there is residual function in the affected area, suggesting viable tissue at risk of damage.Embolic strokes often occur during the day; headache may precede neurologic deficits. Thrombi tend to occur during the night and thus are first noticed on awakening.Lacunar infarcts may produce one of the classic lacunar syndromes (eg, pure motor hemiparesis, pure sensory hemianesthesia, ataxic hemiparesis, dysarthria–clumsy hand syndrome); signs of cortical dysfunction (eg, aphasia) are absent. Multiple lacunar infarcts may result in multi-infarct dementia.A seizure may occur at stroke onset, more often with embolic than thrombotic stroke. Seizures may also occur months to years later; late seizures result from scarring or hemosiderin deposition at the site of ischemia.Deterioration during the first 48 to 72 h after onset of symptoms, particularly progressively impaired consciousness, results more often from cerebral edema than from extension of the infarct. Unless the infarct is large or extensive, function commonly improves within the first few days; further improvement occurs gradually for up to 1 yr.

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ologySymptoms and SignsDiagnosisPrimarily clinical evaluationNeuroimaging and bedside glucose testingEvaluation to identify the causeDiagnosis of ischemic stroke is suggested by sudden neurologic deficits referable to a specific arterial territory. Ischemic stroke must be distinguished from other causes of similar focal deficits (sometimes called stroke mimics), such asHypoglycemiaPostictal [Todd] paralysis (a transient neurologic deficit, usually weakness, of the limb contralateral to the seizure focus)Hemorrhagic strokeRarely, migraineHeadache, coma or stupor, and vomiting are more likely with hemorrhagic stroke.Differentiating clinically between the types of stroke is imprecise; however, some clues based on symptom progression, time of onset, and type of deficit can help.Although diagnosis is clinical, neuroimaging and bedside glucose testing are mandatory. CT is done first to exclude intracerebral hemorrhage, subdural or epidural hematoma, and a rapidly growing, bleeding, or suddenly symptomatic tumor. CT evidence of even a large anterior circulation ischemic stroke may be subtle during the first few hours; changes may include effacement of sulci or the insular cortical ribbon, loss of the gray-white junction between cortex and white matter, and a dense middle cerebral artery sign. Within 6 to 12 h of ischemia, medium-sized to large infarcts start to become visible as hypodensities; small infarcts (eg, lacunar infarcts) may be visible only with MRI. Diffusion-weighted MRI (highly sensitive for early ischemia) can be done immediately after initial CT neuroimaging.Ischemic Stroke ImagingDistinction between lacunar, embolic, and thrombotic stroke based on history, examination, and neuroimaging is not always reliable, so tests to identify common or treatable causes and risk factors for all of these types of strokes are routinely done. Patients should be evaluated for the following categories of causes and risk factors:Cardiac (eg, atrial fibrillation, potential structural sources of emboli)Vascular (eg, critical arterial stenosis)Blood (eg, hypercoagulability)For cardiac causes, testing typically includes ECG, telemetry or Holter monitoring, serum troponin, and transthoracic or transesophageal echocardiography.For vascular causes, testing may include magnetic resonance angiography (MRA), CT angiography (CTA), carotid and transcranial duplex ultrasonography, and conventional angiography. The choice and sequence of testing is individualized, based on clinical findings. MRA, CTA, and carotid ultrasonography all show the anterior circulation; however, MRA and CTA provide better images of the posterior circulation than carotid ultrasonography. MRA is generally preferred to CTA if patients can remain still during MRA (to avoid motion artifact).For blood-related causes (eg, thrombotic disorders), blood tests are done to assess their contribution and that of other causes. Routine testing typically includes CBC, platelet count, PT/PTT, fasting blood glucose, and lipid profile.Depending on which causes are clinically suspected, additional tests may include measurement of homocysteine, testing for thrombotic disorders (antiphospholipid antibodies, protein S, protein C, antithrombin III, factor V Leiden), testing for rheumatic disorders (eg, antinuclear antibodies, rheumatoid factor, ESR), syphilis serologic testing, Hb electrophoresis, and a urine drug screen for cocaine and amphetamines.A cause cannot be identified

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PrognosisStroke severity and progression are often assessed using standardized measures such as the National Institutes of Health (NIH) Stroke Scale (see Table: The National Institutes of Health Stroke Scale*); the score on this scale correlates with extent of functional impairment and prognosis. During the first days, progression and outcome can be difficult to predict. Older age, impaired consciousness, aphasia, and brain stem signs suggest a poor prognosis. Early improvement and younger age suggest a favorable prognosis.CLINICAL CALCULATOR:NIH Stroke ScoreiconTABLEThe National Institutes of Health Stroke Scale*iconAbout 50% of patients with moderate or severe hemiplegia and most with milder deficits have a clear sensorium and eventually can take care of their basic needs and walk adequately. Complete neurologic recovery occurs in about 10%. Use of the affected limb is usually limited, and most deficits that remain after 12 mo are permanent. Patients who have had a stroke are at high risk of subsequent strokes and each tends to worsen neurologic function. About 25% of patients who recover from a first stroke have another stroke within 5 yr.After an ischemic stroke, about 20% of patients die in the hospital; mortality rate increases with age.

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TreatmentGeneral stroke treatmentsAcute antihypertensive therapy only in certain circumstancesAntiplatelet therapyFor acute treatment, sometimes reperfusion with recombinant tissue plasminogen activator (IV or thrombolysis-in-situ), and/or mechanical thrombectomySometimes anticoagulationLong-term control of risk factorsSometimes carotid endarterectomy or stentingAcute stroke treatmentGuidelines for early management of stroke are available from the American Heart Association and American Stroke Association. Patients with acute ischemic strokes are usually hospitalized. Supportive measures may be needed during initial evaluation just

and stabilization.Perfusion of an ischemic brain area may require a high BP because autoregulation is lost; thus, BP should not be decreased except in the following cases:BP is > 220 mm Hg systolic or > 120 mm Hg diastolic on 2 successive readings > 15 min apart.There are signs of other end-organ damage (eg, aortic dissection, acute MI, pulmonary edema, hypertensive encephalopathy, retinal hemorrhages, acute renal failure).Use of recombinant tPA and/or mechanical thrombectomy is likely.To lower BP, clinicians can give nicardipine 2.5 mg/h IV initially; dose is increased by 2.5 mg/h q 5 min to a maximum of 15 mg/h as needed to decrease systolic BP by 10 to 15%. Alternatively, IV labetalol 20 mg IV can be given over 2 min; if response is inadequate, 40 to 80 mg can be given every 10 min up to a total dose of 300 mg.Patients with presumed thrombi or emboli may be treated with one or a combination of the following:tPA, thrombolysis-in-situ, and/or mechanical thrombectomy (1)Antiplatelet drugsAnticoagulantsMost patients are not candidates for thrombolytic therapy; they should be given an antiplatelet drug (usually aspirin 325 mg po) when they are admitted to the hospital. Contraindications to antiplatelet drugs include aspirin-induced or NSAID-induced asthma or urticaria, other hypersensitivity to aspirin or to tartrazine, acute GI bleeding, G6PD deficiency, and use of warfarin.Recombinant tPA can be used for patients with acute ischemic stroke up to 3 h after symptom onset if they have no contraindications to tPA (see Table: Exclusion Criteria for Use of Tissue Plasminogen Activator in Stroke). Some experts recommend using tPA up to 4.5 h after symptom onset (see Expansion of the Time Window for Treatment of Acute Ischemic Stroke With Intravenous Tissue Plasminogen Activator); however, between 3 h and 4.5 h after symptom onset, additional exclusion criteria apply (see Table: Exclusion Criteria for Use of Tissue Plasminogen Activator in Stroke). Although tPA can cause fatal or other symptomatic brain hemorrhage, patients treated with tPA strictly according to protocols still have a higher likelihood of functional neurologic recovery. Only physicians experienced in stroke management should use tPA to treat patients with acute stroke; inexperienced physicians are more likely to violate protocols, resulting in more brain hemorrhages and deaths. When tPA is given incorrectly (eg, when given despite the presence of exclusion criteria), risk of hemorrhage due to tPA is high mainly for patients who have had stroke; risk of brain hemorrhage is very low (about 0.5%; 95% confidence interval of 0 to 2.0% [2]) for patients who have had a stroke mimic. If experienced physicians are not available on site, consultation with an expert at a stroke center (including video evaluation of the patient [telemedicine]), if possible, may enable these physicians to use tPA. Because most poor outcomes result from failure to strictly adhere to the protocol, a checklist of inclusion and exclusion criteria should be used.tPA must be given within 4.5 h of symptom onset—a difficult requirement. Because the precise time of symptom onset may not be known, clinicians must start timing from the moment the patient was last observed to be well.Before treatment with tPA, the following are required:Brain hemorrhage must be excluded by CT.Systolic BP must be < 185 mm Hg.Diastolic BP must be < 110 mm Hg.Antihypertensive drugs (IV nicardipine, IV labetalol) may be given as above.Dose of tPA is 0.9 mg/kg IV (maximum dose 90 mg); 10% is given by rapid IV injection, and the remainder by constant infusion over 60 min. Vital signs are closely monitored for 24 h after treatment, and BP is maintained below 185 mm Hg systolic and 110 mm Hg diastolic. Any bleeding complications are aggressively managed. Anticoagulants and antiplatelet drugs are not used within 24 h of treatment with tPA.TABLEExclusion Criteria for Use of Tissue Plasminogen Activator in StrokeiconThrombolysis-in-situ (angiographically directed intra-arterial thrombolysis) of a thrombus or embolus can sometimes be used for major strokes if symptoms began < 6 h ago, particularly for strokes that are due to large occlusions in the middle cerebral artery and cannot be treated with IV recombinant tPA. Clots in the basilar artery may be intra-arterially lysed up to 12 h after stroke onset, sometimes even later depending on the clinical circumstances. This treatment, although standard of care in some large stroke centers, is often unavailable in other hospitals.Mechanical thrombectomy (angiographically directed intra-arterial removal of a thrombus or embolus by a stent retriever device) is often used to treat patients who have had a severe stroke and have an NIH stroke score ≥ 6 when IV and/or intra-arterial thrombolysis has been ineffective; it must be done within 6 h of symptom onset (1). Mechanical thrombectomy may be part of standard of care in large stroke centers. It should not be used outside of a stroke center and should not be used instead of IV recombinant tPA within 4.5 h of onset of symptoms in eligible patients with acute ischemic stroke. Devices used to remove thrombi are being improved, and recent models reestablish perfusion in 90 to 100% of patients. It is unclear whether clinical outcomes are better after successful mechanical reperfusion than after treatment with IV tPA; evidence suggests that the earlier reperfusion is achieved, the better the outcome regardless how it is achieved.In some stroke centers, IV tPA, thrombolysis in situ, and/or mechanical thrombectomy are sometimes done based on imaging criteria (tissue-based criteria) rather than on time after symptom onset (time-based criteria). Tissue-based criteria can be used when time of symptom onset cannot be established (eg, if a patient awakens with stroke symptoms after sleeping several hours or if a patient has aphasia and cannot provide a time frame). To determine eligibility, clinicians use imaging to identify potentially salvageable brain tissue (also called penumbral tissue). The volume of infarcted tissue identified by diffusion-weighted MRI is compared with the volume of at-risk underperfused tissue identified by perfusion-weighted MRI or CT. A sizeable mismatch between the volumes identified by diffusion-weighted and perfusion-weighted imaging suggests that substantial penumbral tissue may still be rescued, and thus thrombolysis and/or thrombectomy is indicated. However, time-based criteria are still used in clinical practice; studies to determine whether outcomes are better using tissue- or time-based criteria are ongoing.Anticoagulation with heparin or low molecular weight heparin is used for stroke caused by cerebral venous thrombosis and is sometimes used for emboli due to atrial fibrillation and for stroke due to presumed progressive thrombosis if it continues to evolve despite use of antiplatelet drugs and cannot be treated any other way (eg, with tPA or invasive methods). In one large series, outcomes after treatment of basilar artery thrombosis with IV heparin plus IV tPA were as good as or better than those after treatment with endovascular therapies. Warfarin is begun simultaneously with heparin. Before anticoagulation, hemorrhage must be excluded by CT. Constant weight-based heparin infusion (see Figure: Weight-based heparin dosing) is used to increase PTT to 1.5 to 2 times baseline values until warfarin has increased the INR to 2 to 3 (3 in hypercoagulable disorders). Because warfarin predisposes to bleeding and is continued after hospital discharge, its use should be restricted to patients who are likely to comply with dosage and monitoring requirements and who are not prone to falls.Long-term stroke treatmentSupportive care is continued during convalescence. Controlling hyperglycemia and fever can limit brain damage after stroke, leading to better functional outcomes.Long-term management also focuses on prevention of recurrent stroke (secondary prevention). Modifiable risk factors (eg, hypertension, diabetes, smoking, alcoholism, dyslipidemia, obesity) are treated. Reducing systolic BP may be more effective when the target BP is < 120 mm Hg rather than the typical level (< 140 mm Hg).Extracranial carotid endarterectomy or stenting is indicated for patients with recent nondisabling, submaximal stroke attributed to an ipsilateral carotid obstruction of 70 to 99% of the arterial lumen or to an ulcerated plaque if life expectancy is at least 5 yr. In other symptomatic patients (eg, patients with TIAs), endarterectomy or stenting with antiplatelet therapy is indicated for carotid obstruction of ≥ 60% with or without ulceration if life expectancy is at least 5 yr. These procedures should be done by surgeons and interventionists who have a successful record with the procedure (ie, morbidity and mortality rate of < 3%) in the hospital where it will be done. If carotid stenosis is asymptomatic, endarterectomy or stenting is beneficial only when done by very experienced surgeons or interventionists, and that benefit is likely to be small. For many patients, carotid stenting with an emboli-protection device (a type of filter) is preferred to endarterectomy, particularly if patients are < 70 yr and have a high surgical risk. Carotid endarterectomy and stenting are equally effective for stroke prevention. In the periprocedural period, MI is more likely after endarterectomy, and recurrent stroke is more likely after stenting.Extracranial vertebral angioplasty and/or stenting can be used in certain patients with recurrent symptoms of vertebrobasilar ischemia despite optimal medical treatment and a vertebral artery obstruction of 50 to 99%.Intracranial major artery angioplasty and/or stenting is considered investigational for patients with recurrent stroke or TIA symptoms despite optimal medical treatment and a 50 to 99% obstruction of a major intracranial artery.Endovascular closure of a patent foramen ovale does not appear to be more effective for preventing strokes than medical management, but studies are ongoing.Oral antiplatelet drugs are used to prevent subsequent noncardioembolic (atherothrombotic, lacunar, cryptogenic) strokes (secondary prevention). The following may be used:Aspirin 81 or 325 mg once/dayClopidogrel 75 mg once/dayThe combination product aspirin 25 mg/extended-release dipyridamole 200 mg bidIn patients taking warfarin, antiplatelet drugs additively increase risk of bleeding and are thus usually avoided; however, aspirin is occasionally used simultaneously with warfarin in certain high-risk patients. Clopidogrel is indicated for patients who are allergic to aspirin. If ischemic stroke recurs or if a coronary artery stent becomes blocked while patients are taking clopidogrel, clinicians should suspect impaired metabolism of clopidogrel (ineffective conversion of clopidogrel to its active form because CYP2C19 activity is reduced); a test to determine CYP2C19 status (eg, genetic testing for CYP450 polymorphisms) is recommended. If impaired metabolism is confirmed, aspirin or the combination product aspirin/extended-release dipyridamole is a reasonable alternative.If patients have had a TIA or minor stroke, clopidogrel plus aspirin given within 24 h of symptom onset appears more effective than aspirin alone for reducing risk of stroke in the first 90 days and does not increase risk of hemorrhage. However, prolonged (eg, > 6 mo) use of clopidogrel plus aspirin is avoided because it has no advantage over aspirin alone in long-term secondary stroke prevention and results in more bleeding complications. Clopidogrel plus aspirin before and for ≥ 30 days after stenting is indicated, usually for ≤ 6 mo; if patients cannot tolerate clopidogrel, ticlopidine 250 mg bid can be substituted.Oral anticoagulants are indicated for secondary prevention of cardioembolic strokes (as well as primary prevention). Adjusted-dose warfarin (a vitamin K antagonist) with a target INR of 2 to 3 is used for certain patients with nonvalvular or valvular atrial fibrillation. A target INR of 2.5 to 3.5 is used if patients have a mechanical prosthetic cardiac valve. Efficacious alternatives to warfarin for patients with nonvalvular atrial fibrillation include the following new anticoagulants:Dabigatran (a direct thrombin inhibitor) 150 mg bid in patients without severe renal failure (creatinine clearance < 15 mL/min) and/or liver failure (elevated INR)Apixaban (a direct factor Xa inhibitor) 5 mg bid in patients ≥ 80 yr, in patients with serum creatinine ≥ 1.5 mg/dL and creatinine clearance ≥ 25 mL/min, or as an alternative to aspirin in patients who cannot take warfarinRivaroxaban (a direct factor Xa inhibitor) 20 mg once/day for patients without severe renal failure (creatinine clearance < 15 mL/min)The main advantage of these new anticoagulants is ease of use (eg, no need to check anticoagulation level with a blood test after the initial dose or to use a parenteral anticoagulant such as unfractionated heparin given by continuous infusion when transitioning from parenteral to oral anticoagulants). Their main disadvantage is lack of an antidote to reverse anticoagulation in case a hemorrhagic complication occurs; the exception is dabigatran, for which idarucizumab is an antidote (4). Efficacy and safety of combining any of these new anticoagulants with an antiplatelet drug have not been established.Statins are used to prevent recurrent strokes; lipid levels must be decreased by substantial amounts. Atorvastatin 80 mg once/day is recommended for patients with evidence of atherosclerotic stroke and LDL (low-density lipoprotein) cholesterol ≥ 100 mg/dL. A reasonable LDL cholesterol target is a 50% reduction or a level of < 70 mg/dL. Other statins (eg, simvastatin, pravastatin) may be also used.

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QLogoMERCK MANUALProfessional VersionSearch HOMEMEDICAL TOPICSRESOURCESDRUG INFONEWSPROCEDURESQUIZZES & CASESABOUTLogoMERCK MANUALProfessional VersionMEDICAL TOPICS & CHAPTERSABCDEFGHIJKLMNOPQRSTUVWXYZ PROFESSIONAL / NEUROLOGIC DISORDERS / STROKE / ISCHEMIC STROKEIN THIS TOPICEtiologyPathophysiologySymptoms and SignsDiagnosisPrognosisTreatmentAcute stroke treatmentLong-term stroke treatmentTreatment referencesKey PointsOTHER TOPICS IN THIS CHAPTEROverview of StrokeIschemic StrokeTransient Ischemic Attack (TIA)Intracerebral HemorrhageSubarachnoid Hemorrhage (SAH)TEST YOUR KNOWLEDGEMigraineWhich of the following is associated with stroke in women who have migraine with aura? Oral contraceptives Red wine Sleep deprivation Temporomandibular joint dysfunction Click here for Veterinary contentNEWS & VIDEOSUltra-Early Neurological Deterioration Common in Stroke NewsUltra-Early Neurological Deterioration Common in StrokeFRIDAY, Aug. 3, 2018 (HealthDay News) -- Ultra-early neurological deterioration (U-END) occurs in one in eight ambulance-transported patients with acute cerebrovascular disease and is associated... View Article >All News >Brain Vasculature 3D ModelBrain VasculatureView 3D Model >All 3D Models >How to do a 4-Minute Neurologic Exam VideoHow to do a 4-Minute Neurologic ExamView Video >All Videos >SOCIAL MEDIAMORE+FacebookFollowyoutubeFollowTwitterFollowPinterestFollowinstagramFollowShareAdd to Any PlatformIschemic StrokeBy Elias A. Giraldo, MD, MS, California University of Science and Medicine School of MedicineCLICK HERE FOR PATIENT EDUCATIONNOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer VersionIschemic stroke is sudden neurologic deficits that result from focal cerebral ischemia associated with permanent brain infarction (eg, positive results on diffusion-weighted MRI). Common causes are (from most to least common) atherothrombotic occlusion of large arteries; cerebral embolism (embolic infarction); nonthrombotic occlusion of small, deep cerebral arteries (lacunar infarction); and proximal arterial stenosis with hypotension that decreases cerebral blood flow in arterial watershed zones (hemodynamic stroke). Diagnosis is clinical, but CT or MRI is done to exclude hemorrhage and confirm the presence and extent of stroke. Thrombolytic therapy may be useful acutely in certain patients. Depending on the cause of stroke, carotid endarterectomy or stenting, antiplatelet drugs, or warfarin may help reduce risk of subsequent strokes.EtiologyThe following are the modifiable risk factors that contribute the most to increased risk of ischemic stroke:HypertensionCigarette smokingDyslipidemiaDiabetesInsulin resistance (1)Abdominal obesityAlcoholismLack of physical activityHigh-risk diet (eg, high in saturated fats, trans fats, and calories)Psychosocial stress (eg, depression)Heart disorders (particularly disorders that predispose to emboli, such as acute MI, infective endocarditis, and atrial fibrillation)Use of certain drugs (eg, cocaine, amphetamines)HypercoagulabilityVasculitisUnmodifiable risk factors include the following:Prior strokeOlder ageFamily history of strokeIschemia usually results from thrombi or emboli. Even infarcts classified as lacunar based on clinical criteria (morphology, size, and location) often involve small thrombi or emboli.ThrombosisAtherothrombotic occlusion of large arteries (thrombus superimposed on an atherosclerotic artery) is the most common cause of ischemic stroke.Atheromas, particularly if ulcerated, predispose to thrombi. Atheromas can occur in any major cerebral artery and are common at areas of turbulent flow, particularly at the carotid bifurcation. Partial or complete thrombotic occlusion occurs most often at the main trunk of the middle cerebral artery and its branches but is also common in the large arteries at the base of the brain, in deep perforating arteries, and in small cortical branches. The basilar artery and the segment of the internal carotid artery between the cavernous sinus and supraclinoid process are often occluded.Less common causes of thrombosis include vascular inflammation secondary to disorders such as acute or chronic meningitis, vasculitic disorders, and syphilis; dissection of intracranial arteries or the aorta; hypercoagulability disorders (eg, antiphospholipid syndrome, hyperhomocysteinemia); hyperviscosity disorders (eg, polycythemia, thrombocytosis, hemoglobinopathies, plasma cell disorders); and rare disorders (eg, fibromuscular dysplasia, moyamoya disease, Binswanger disease). Older oral contraceptive formulations increase risk of thrombosis. In children, sickle cell disease is a common cause of ischemic stroke.EmbolismEmboli may lodge anywhere in the cerebral arterial tree.Emboli may originate as cardiac thrombi, especially in the following conditions:Atrial fibrillationRheumatic heart disease (usually mitral stenosis)Post-MIVegetations on heart valves in bacterial or marantic endocarditisProsthetic heart valvesMechanical circulatory assist devices (eg, left ventricular assist device, or LVAD [2])Other sources include clots that form after open-heart surgery and atheromas in neck arteries or in the aortic arch. Rarely, emboli consist of fat (from fractured long bones), air (in decompression sickness), or venous clots that pass from the right to the left side of the heart through a patent foramen ovale with shunt (paradoxical emboli). Emboli may dislodge spontaneously or after invasive cardiovascular procedures (eg, catheterization). Rarely, thrombosis of the subclavian artery results in embolic stroke in the vertebral artery or its branches.Lacunar infarctsIschemic stroke can also result from lacunar infarcts. These small (≤ 1.5 cm) infarcts result from nonatherothrombotic obstruction of small, perforating arteries that supply deep cortical structures; the usual cause is lipohyalinosis (degeneration of the media of small arteries and replacement by lipids and collagen). Whether emboli cause lacunar infarcts is controversial.Lacunar infarcts tend to occur in elderly patients with diabetes or poorly controlled hypertension.Other causesAny factor that impairs systemic perfusion (eg, carbon monoxide toxicity, severe anemia or hypoxia, polycythemia, hypotension) increases risk of all types of ischemic strokes. A stroke may occur along the borders between territories of arteries (watershed areas); in such areas, blood supply is normally low, particularly if patients have hypotension and/or if major cerebral arteries are stenotic.Less commonly, ischemic stroke results from vasospasm (eg, during migraine, after subarachnoid hemorrhage, after use of sympathomimetic drugs such as cocaine or amphetamines) or venous sinus thrombosis (eg, during intracranial infection, postoperatively, peripartum, secondary to a hypercoagulability disorder).Etiology references1. Kernan WN, Viscoli CM, Furie KL, et al: Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med 374 (14):1321–1331, 2016. doi: 10.1056/NEJMoa1506930.2. Morgan JA, Brewer RJ, Nemeh HW, et al: Stroke while on long-term left ventricular assist device support: incidence, outcome, and predictors. ASAIO J 60 (3):284–289, 2014. doi: 10.1097/MAT.0000000000000074.PathophysiologyInadequate blood flow in a single brain artery can often be compensated for by an efficient collateral system, particularly between the carotid and vertebral arteries via anastomoses at the circle of Willis and, to a lesser extent, between major arteries supplying the cerebral hemispheres. However, normal variations in the circle of Willis and in the caliber of various collateral vessels, atherosclerosis, and other acquired arterial lesions can interfere with collateral flow, increasing the chance that blockage of one artery will cause brain ischemia.Some neurons die when perfusion is < 5% of normal for > 5 min; however, the extent of damage depends on the severity of ischemia. If it is mild, damage proceeds slowly; thus, even if perfusion is 40% of normal, 3 to 6 h may elapse before brain tissue is completely lost. However, if severe ischemia persists > 15 to 30 min, all of the affected tissue dies (infarction). Damage occurs more rapidly during hyperthermia and more slowly during hypothermia. If tissues are ischemic but not yet irreversibly damaged, promptly restoring blood flow may reduce or reverse injury. For example, intervention may be able to salvage the moderately ischemic areas (penumbras) that often surround areas of severe ischemia (these areas exist because of collateral flow).Mechanisms of ischemic injury includeEdemaMicrovascular thrombosisProgrammed cell death (apoptosis)Infarction with cell necrosisInflammatory mediators (eg, IL-1B, tumor necrosis factor-alpha) contribute to edema and microvascular thrombosis. Edema, if severe or extensive, can increase intracranial pressure.Many factors may contribute to necrotic cell death; they include loss of ATP stores, loss of ionic homeostasis (including intracellular calcium accumulation), lipid peroxidative damage to cell membranes by free radicals (an iron-mediated process), excitatory neurotoxins (eg, glutamate), and intracellular acidosis due to accumulation of lactate.Symptoms and SignsSymptoms and signs of ischemic stroke depend on the part of brain affected. Patterns of neurologic deficits often suggest the affected artery (see Table: Selected Stroke Syndromes), but correlation is often inexact.TABLESelected Stroke Syndromes iconDeficits may become maximal within several minutes of onset, typically in embolic stroke. Less often, deficits evolve slowly, usually over 24 to 48 h (called evolving stroke or stroke in evolution), typically in atherothrombotic stroke. In most evolving strokes, unilateral neurologic dysfunction (often beginning in one arm, then spreading ipsilaterally) extends without causing headache, pain, or fever. Progression is usually stepwise, interrupted by periods of stability. A stroke is considered submaximal when after it is complete, there is residual function in the affected area, suggesting viable tissue at risk of damage.Embolic strokes often occur during the day; headache may precede neurologic deficits. Thrombi tend to occur during the night and thus are first noticed on awakening.Lacunar infarcts may produce one of the classic lacunar syndromes (eg, pure motor hemiparesis, pure sensory hemianesthesia, ataxic hemiparesis, dysarthria–clumsy hand syndrome); signs of cortical dysfunction (eg, aphasia) are absent. Multiple lacunar infarcts may result in multi-infarct dementia.A seizure may occur at stroke onset, more often with embolic than thrombotic stroke. Seizures may also occur months to years later; late seizures result from scarring or hemosiderin deposition at the site of ischemia.Deterioration during the first 48 to 72 h after onset of symptoms, particularly progressively impaired consciousness, results more often from cerebral edema than from extension of the infarct. Unless the infarct is large or extensive, function commonly improves within the first few days; further improvement occurs gradually for up to 1 yr.DiagnosisPrimarily clinical evaluationNeuroimaging and bedside glucose testingEvaluation to identify the causeDiagnosis of ischemic stroke is suggested by sudden neurologic deficits referable to a specific arterial territory. Ischemic stroke must be distinguished from other causes of similar focal deficits (sometimes called stroke mimics), such asHypoglycemiaPostictal [Todd] paralysis (a transient neurologic deficit, usually weakness, of the limb contralateral to the seizure focus)Hemorrhagic strokeRarely, migraineHeadache, coma or stupor, and vomiting are more likely with hemorrhagic stroke.Differentiating clinically between the types of stroke is imprecise; however, some clues based on symptom progression, time of onset, and type of deficit can help.Although diagnosis is clinical, neuroimaging and bedside glucose testing are mandatory. CT is done first to exclude intracerebral hemorrhage, subdural or epidural hematoma, and a rapidly growing, bleeding, or suddenly symptomatic tumor. CT evidence of even a large anterior circulation ischemic stroke may be subtle during the first few hours; changes may include effacement of sulci or the insular cortical ribbon, loss of the gray-white junction between cortex and white matter, and a dense middle cerebral artery sign. Within 6 to 12 h of ischemia, medium-sized to large infarcts start to become visible as hypodensities; small infarcts (eg, lacunar infarcts) may be visible only with MRI. Diffusion-weighted MRI (highly sensitive for early ischemia) can be done immediately after initial CT neuroimaging.Ischemic Stroke ImagingDistinction between lacunar, embolic, and thrombotic stroke based on history, examination, and neuroimaging is not always reliable, so tests to identify common or treatable causes and risk factors for all of these types of strokes are routinely done. Patients should be evaluated for the following categories of causes and risk factors:Cardiac (eg, atrial fibrillation, potential structural sources of emboli)Vascular (eg, critical arterial stenosis)Blood (eg, hypercoagulability)For cardiac causes, testing typically includes ECG, telemetry or Holter monitoring, serum troponin, and transthoracic or transesophageal echocardiography.For vascular causes, testing may include magnetic resonance angiography (MRA), CT angiography (CTA), carotid and transcranial duplex ultrasonography, and conventional angiography. The choice and sequence of testing is individualized, based on clinical findings. MRA, CTA, and carotid ultrasonography all show the anterior circulation; however, MRA and CTA provide better images of the posterior circulation than carotid ultrasonography. MRA is generally preferred to CTA if patients can remain still during MRA (to avoid motion artifact).For blood-related causes (eg, thrombotic disorders), blood tests are done to assess their contribution and that of other causes. Routine testing typically includes CBC, platelet count, PT/PTT, fasting blood glucose, and lipid profile.Depending on which causes are clinically suspected, additional tests may include measurement of homocysteine, testing for thrombotic disorders (antiphospholipid antibodies, protein S, protein C, antithrombin III, factor V Leiden), testing for rheumatic disorders (eg, antinuclear antibodies, rheumatoid factor, ESR), syphilis serologic testing, Hb electrophoresis, and a urine drug screen for cocaine and amphetamines.A cause cannot be identified for some strokes (cryptogenic strokes).PrognosisStroke severity and progression are often assessed using standardized measures such as the National Institutes of Health (NIH) Stroke Scale (see Table: The National Institutes of Health Stroke Scale*); the score on this scale correlates with extent of functional impairment and prognosis. During the first days, progression and outcome can be difficult to predict. Older age, impaired consciousness, aphasia, and brain stem signs suggest a poor prognosis. Early improvement and younger age suggest a favorable prognosis.CLINICAL CALCULATOR:NIH Stroke Score iconTABLEThe National Institutes of Health Stroke Scale* iconAbout 50% of patients with moderate or severe hemiplegia and most with milder deficits have a clear sensorium and eventually can take care of their basic needs and walk adequately. Complete neurologic recovery occurs in about 10%. Use of the affected limb is usually limited, and most deficits that remain after 12 mo are permanent. Patients who have had a stroke are at high risk of subsequent strokes and each tends to worsen neurologic function. About 25% of patients who recover from a first stroke have another stroke within 5 yr.After an ischemic stroke, about 20% of patients die in the hospital; mortality rate increases with age.TreatmentGeneral stroke treatmentsAcute antihypertensive therapy only in certain circumstancesAntiplatelet therapyFor acute treatment, sometimes reperfusion with recombinant tissue plasminogen activator (IV or thrombolysis-in-situ), and/or mechanical thrombectomySometimes anticoagulationLong-term control of risk factorsSometimes carotid endarterectomy or stentingAcute stroke treatmentGuidelines for early management of stroke are available from the American Heart Association and American Stroke Association. Patients with acute ischemic strokes are usually hospitalized. Supportive measures may be needed during initial evaluation and stabilization.Perfusion of an ischemic brain area may require a high BP because autoregulation is lost; thus, BP should not be decreased except in the following cases:BP is > 220 mm Hg systolic or > 120 mm Hg diastolic on 2 successive readings > 15 min apart.There are signs of other end-organ damage (eg, aortic dissection, acute MI, pulmonary edema, hypertensive encephalopathy, retinal hemorrhages, acute renal failure).Use of recombinant tPA and/or mechanical thrombectomy is likely.To lower BP, clinicians can give nicardipine 2.5 mg/h IV initially; dose is increased by 2.5 mg/h q 5 min to a maximum of 15 mg/h as needed to decrease systolic BP by 10 to 15%. Alternatively, IV labetalol 20 mg IV can be given over 2 min; if response is inadequate, 40 to 80 mg can be given every 10 min up to a total dose of 300 mg.Patients with presumed thrombi or emboli may be treated with one or a combination of the following:tPA, thrombolysis-in-situ, and/or mechanical thrombectomy (1)Antiplatelet drugsAnticoagulantsMost patients are not candidates for thrombolytic therapy; they should be given an antiplatelet drug (usually aspirin 325 mg po) when they are admitted to the hospital. Contraindications to antiplatelet drugs include aspirin-induced or NSAID-induced asthma or urticaria, other hypersensitivity to aspirin or to tartrazine, acute GI bleeding, G6PD deficiency, and use of warfarin.Recombinant tPA can be used for patients with acute ischemic stroke up to 3 h after symptom onset if they have no contraindications to tPA (see Table: Exclusion Criteria for Use of Tissue Plasminogen Activator in Stroke). Some experts recommend using tPA up to 4.5 h after symptom onset (see Expansion of the Time Window for Treatment of Acute Ischemic Stroke With Intravenous Tissue Plasminogen Activator); however, between 3 h and 4.5 h after symptom onset, additional exclusion criteria apply (see Table: Exclusion Criteria for Use of Tissue Plasminogen Activator in Stroke). Although tPA can cause fatal or other symptomatic brain hemorrhage, patients treated with tPA strictly according to protocols still have a higher likelihood of functional neurologic recovery. Only physicians experienced in stroke management should use tPA to treat patients with acute stroke; inexperienced physicians are more likely to violate protocols, resulting in more brain hemorrhages and deaths. When tPA is given incorrectly (eg, when given despite the presence of exclusion criteria), risk of hemorrhage due to tPA is high mainly for patients who have had stroke; risk of brain hemorrhage is very low (about 0.5%; 95% confidence interval of 0 to 2.0% [2]) for patients who have had a stroke mimic. If experienced physicians are not available on site, consultation with an expert at a stroke center (including video evaluation of the patient [telemedicine]), if possible, may enable these physicians to use tPA. Because most poor outcomes result from failure to strictly adhere to the protocol, a checklist of inclusion and exclusion criteria should be used.tPA must be given within 4.5 h of symptom onset—a difficult requirement. Because the precise time of symptom onset may not be known, clinicians must start timing from the moment the patient was last observed to be well.Before treatment with tPA, the following are required:Brain hemorrhage must be excluded by CT.Systolic BP must be < 185 mm Hg.Diastolic BP must be < 110 mm Hg.Antihypertensive drugs (IV nicardipine, IV labetalol) may be given as above.Dose of tPA is 0.9 mg/kg IV (maximum dose 90 mg); 10% is given by rapid IV injection, and the remainder by constant infusion over 60 min. Vital signs are closely monitored for 24 h after treatment, and BP is maintained below 185 mm Hg systolic and 110 mm Hg diastolic. Any bleeding complications are aggressively managed. Anticoagulants and antiplatelet drugs are not used within 24 h of treatment with tPA.TABLEExclusion Criteria for Use of Tissue Plasminogen Activator in Stroke iconThrombolysis-in-situ (angiographically directed intra-arterial thrombolysis) of a thrombus or embolus can sometimes be used for major strokes if symptoms began < 6 h ago, particularly for strokes that are due to large occlusions in the middle cerebral artery and cannot be treated with IV recombinant tPA. Clots in the basilar artery may be intra-arterially lysed up to 12 h after stroke onset, sometimes even later depending on the clinical circumstances. This treatment, although standard of care in some large stroke centers, is often unavailable in other hospitals.Mechanical thrombectomy (angiographically directed intra-arterial removal of a thrombus or embolus by a stent retriever device) is often used to treat patients who have had a severe stroke and have an NIH stroke score ≥ 6 when IV and/or intra-arterial thrombolysis has been ineffective; it must be done within 6 h of symptom onset (1). Mechanical thrombectomy may be part of standard of care in large stroke centers. It should not be used outside of a stroke center and should not be used instead of IV recombinant tPA within 4.5 h of onset of symptoms in eligible patients with acute ischemic stroke. Devices used to remove thrombi are being improved, and recent models reestablish perfusion in 90 to 100% of patients. It is unclear whether clinical outcomes are better after successful mechanical reperfusion than after treatment with IV tPA; evidence suggests that the earlier reperfusion is achieved, the better the outcome regardless how it is achieved.In some stroke centers, IV tPA, thrombolysis in situ, and/or mechanical thrombectomy are sometimes done based on imaging criteria (tissue-based criteria) rather than on time after symptom onset (time-based criteria). Tissue-based criteria can be used when time of symptom onset cannot be established (eg, if a patient awakens with stroke symptoms after sleeping several hours or if a patient has aphasia and cannot provide a time frame). To determine eligibility, clinicians use imaging to identify potentially salvageable brain tissue (also called penumbral tissue). The volume of infarcted tissue identified by diffusion-weighted MRI is compared with the volume of at-risk underperfused tissue identified by perfusion-weighted MRI or CT. A sizeable mismatch between the volumes identified by diffusion-weighted and perfusion-weighted imaging suggests that substantial penumbral tissue may still be rescued, and thus thrombolysis and/or thrombectomy is indicated. However, time-based criteria are still used in clinical practice; studies to determine whether outcomes are better using tissue- or time-based criteria are ongoing.Anticoagulation with heparin or low molecular weight heparin is used for stroke caused by cerebral venous thrombosis and is sometimes used for emboli due to atrial fibrillation and for stroke due to presumed progressive thrombosis if it continues to evolve despite use of antiplatelet drugs and cannot be treated any other way (eg, with tPA or invasive methods). In one large series, outcomes after treatment of basilar artery thrombosis with IV heparin plus IV tPA were as good as or better than those after treatment with endovascular therapies. Warfarin is begun simultaneously with heparin. Before anticoagulation, hemorrhage must be excluded by CT. Constant weight-based heparin infusion (see Figure: Weight-based heparin dosing) is used to increase PTT to 1.5 to 2 times baseline values until warfarin has increased the INR to 2 to 3 (3 in hypercoagulable disorders). Because warfarin predisposes to bleeding and is continued after hospital discharge, its use should be restricted to patients who are likely to comply with dosage and monitoring requirements and who are not prone to falls.Long-term stroke treatmentSupportive care is continued during convalescence. Controlling hyperglycemia and fever can limit brain damage after stroke, leading to better functional outcomes.Long-term management also focuses on prevention of recurrent stroke (secondary prevention). Modifiable risk factors (eg, hypertension, diabetes, smoking, alcoholism, dyslipidemia, obesity) are treated. Reducing systolic BP may be more effective when the target BP is < 120 mm Hg rather than the typical level (< 140 mm Hg).Extracranial carotid endarterectomy or stenting is indicated for patients with recent nondisabling, submaximal stroke attributed to an ipsilateral carotid obstruction of 70 to 99% of the arterial lumen or to an ulcerated plaque if life expectancy is at least 5 yr. In other symptomatic patients (eg, patients with TIAs), endarterectomy or stenting with antiplatelet therapy is indicated for carotid obstruction of ≥ 60% with or without ulceration if life expectancy is at least 5 yr. These procedures should be done by surgeons and interventionists who have a successful record with the procedure (ie, morbidity and mortality rate of < 3%) in the hospital where it will be done. If carotid stenosis is asymptomatic, endarterectomy or stenting is beneficial only when done by very experienced surgeons or interventionists, and that benefit is likely to be small. For many patients, carotid stenting with an emboli-protection device (a type of filter) is preferred to endarterectomy, particularly if patients are < 70 yr and have a high surgical risk. Carotid endarterectomy and stenting are equally effective for stroke prevention. In the periprocedural period, MI is more likely after endarterectomy, and recurrent stroke is more likely after stenting.Extracranial vertebral angioplasty and/or stenting can be used in certain patients with recurrent symptoms of vertebrobasilar ischemia despite optimal medical treatment and a vertebral artery obstruction of 50 to 99%.Intracranial major artery angioplasty and/or stenting is considered investigational for patients with recurrent stroke or TIA symptoms despite optimal medical treatment and a 50 to 99% obstruction of a major intracranial artery.Endovascular closure of a patent foramen ovale does not appear to be more effective for preventing strokes than medical management, but studies are ongoing.Oral antiplatelet drugs are used to prevent subsequent noncardioembolic (atherothrombotic, lacunar, cryptogenic) strokes (secondary prevention). The following may be used:Aspirin 81 or 325 mg once/dayClopidogrel 75 mg once/dayThe combination product aspirin 25 mg/extended-release dipyridamole 200 mg bidIn patients taking warfarin, antiplatelet drugs additively increase risk of bleeding and are thus usually avoided; however, aspirin is occasionally used simultaneously with warfarin in certain high-risk patients. Clopidogrel is indicated for patients who are allergic to aspirin. If ischemic stroke recurs or if a coronary artery stent becomes blocked while patients are taking clopidogrel, clinicians should suspect impaired metabolism of clopidogrel (ineffective conversion of clopidogrel to its active form because CYP2C19 activity is reduced); a test to determine CYP2C19 status (eg, genetic testing for CYP450 polymorphisms) is recommended. If impaired metabolism is confirmed, aspirin or the combination product aspirin/extended-release dipyridamole is a reasonable alternative.If patients have had a TIA or minor stroke, clopidogrel plus aspirin given within 24 h of symptom onset appears more effective than aspirin alone for reducing risk of stroke in the first 90 days and does not increase risk of hemorrhage. However, prolonged (eg, > 6 mo) use of clopidogrel plus aspirin is avoided because it has no advantage over aspirin alone in long-term secondary stroke prevention and results in more bleeding complications. Clopidogrel plus aspirin before and for ≥ 30 days after stenting is indicated, usually for ≤ 6 mo; if patients cannot tolerate clopidogrel, ticlopidine 250 mg bid can be substituted.Oral anticoagulants are indicated for secondary prevention of cardioembolic strokes (as well as primary prevention). Adjusted-dose warfarin (a vitamin K antagonist) with a target INR of 2 to 3 is used for certain patients with nonvalvular or valvular atrial fibrillation. A target INR of 2.5 to 3.5 is used if patients have a mechanical prosthetic cardiac valve. Efficacious alternatives to warfarin for patients with nonvalvular atrial fibrillation include the following new anticoagulants:Dabigatran (a direct thrombin inhibitor) 150 mg bid in patients without severe renal failure (creatinine clearance < 15 mL/min) and/or liver failure (elevated INR)Apixaban (a direct factor Xa inhibitor) 5 mg bid in patients ≥ 80 yr, in patients with serum creatinine ≥ 1.5 mg/dL and creatinine clearance ≥ 25 mL/min, or as an alternative to aspirin in patients who cannot take warfarinRivaroxaban (a direct factor Xa inhibitor) 20 mg once/day for patients without severe renal failure (creatinine clearance < 15 mL/min)The main advantage of these new anticoagulants is ease of use (eg, no need to check anticoagulation level with a blood test after the initial dose or to use a parenteral anticoagulant such as unfractionated heparin given by continuous infusion when transitioning from parenteral to oral anticoagulants). Their main disadvantage is lack of an antidote to reverse anticoagulation in case a hemorrhagic complication occurs; the exception is dabigatran, for which idarucizumab is an antidote (4). Efficacy and safety of combining any of these new anticoagulants with an antiplatelet drug have not been established.Statins are used to prevent recurrent strokes; lipid levels must be decreased by substantial amounts. Atorvastatin 80 mg once/day is recommended for patients with evidence of atherosclerotic stroke and LDL (low-density lipoprotein) cholesterol ≥ 100 mg/dL. A reasonable LDL cholesterol target is a 50% reduction or a level of < 70 mg/dL. Other statins (eg, simvastatin, pravastatin) may be also used.Treatment references1. Powers WJ, Derdeyn CP, Biller J, et al: 2015 American Heart Association/American Stroke Association focused update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke regarding endovascular treatment: A guideline for healthcare professionals From the American Heart Association/American Stroke Association. Stroke 46 (10):3020–3035, 2015. doi: 10.1161/STR.0000000000000074.2. Tsivgoulis G, Zand R, Katsanos AH, et al: Safety of intravenous thrombolysis in stroke mimics: prospective 5-year study and comprehensive meta-analysis. Stroke 46 (5):1281–1287, 2015. doi: 10.1161/STROKEAHA.115.009012.3. Jauch EC, Saver JL, Adams HP Jr, et al: Guidelines for the early management of patients with acute ischemic stroke: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 44 (3):870–947, 2013. doi: 10.1161/STR.0b013e318284056a.4. Pollack CV Jr, Reilly PA, Eikelboom, J, et al: Idarucizumab for dabigatran reversal. N Engl J Med 373:511–520, 2015. doi: 10.1056/NEJMoa1502000.Key PointsDifferentiate ischemic stroke from hypoglycemia, postictal paralysis, hemorrhagic stroke, and migraine.Although clinical differentiation is imprecise, some clues to help differentiate between common types of stroke include symptom progression (maximal deficits within minutes of onset with embolic vs sometimes stepwise or slow onset with thrombotic), time of onset (day with embolic vs night with thrombotic), and type of deficits (eg, specific syndromes and absence of cortical signs with lacunar infarcts).Test patients for cardiac causes (including atrial fibrillation) and arterial stenosis, and do blood tests (eg, for thrombotic, rheumatic, and other disorders as indicated).In general, do not aggressively reduce BP soon after acute ischemic stroke.To determine eligibility for tPA, use a checklist and, when available consult an expert, either in person or via telemedicine.To prevent future ischemic strokes, control modifiable risk factors and treat, when appropriate, with antiplatelet therapy, statin therapy, and/or endarterectomy or stenting.Drugs Mentioned In This ArticleDrug Name Select TradeidarucizumabPRAXBINDAtorvastatinLIPITORdipyridamolePERSANTINEPioglitazoneACTOSRivaroxabanXARELTOticlopidineNo US brand namepravastatinPRAVACHOLClopidogrelPLAVIXnicardipineCARDENEsimvastatinZOCORwarfarinCOUMADINApixabanELIQUISheparinPANHEPRINLast full review/revision February 2017 by Elias A. Giraldo, MD, MSNOTE: This is the Professional Version. CONSUMERS: Click here for the Consumer VersionOverview of Stroke Was This Page Helpful?YESNO Transient Ischemic Attack (TIA) Professionals also readOverview of StrokeOverview of StrokeStroke RehabilitationStroke RehabilitationTransient Ischemic Attack (TIA)Transient Ischemic Attack (TIA)MManualMerck and the Merck ManualsMerck & Co., Inc., Kenilworth, NJ, USA is a global healthcare leader working to help the world be well. From developing new therapies that treat and prevent disease to helping people in need, we are committed to improving health and well-being around the world. The Merck Manual was first published in 1899 as a service to the community. The legacy of this great resource continues as the Merck Manual in the US and Canada and the MSD Manual outside of North America. Learn more about our commitment to Global Medical Knowledge.

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T/F regarding LMWH

Fondaparinaux is superior in efficacy to enoxaparin

A standard dose of fondaparinaux is given to all pts irrespective of their body weight

Dose adjustment is required in renal dysfunction

Anticoagulant effect can be reversed with protamineLevel of anticoagulation can be monitored with activated factor x levels

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Ischemic stroke is sudden neurologic deficits that result from focal cerebral ischemia associated with permanent brain infarction (eg, positive results on diffusion-weighted MRI). Common causes are (from most to least common) atherothrombotic occlusion of large arteries; cerebral embolism (embolic infarction); nonthrombotic occlusion of small, deep cerebral arteries (lacunar infarction); and proximal arterial stenosis with hypotension that decreases cerebral blood flow in arterial watershed zones (hemodynamic stroke). Diagnosis is clinical, but CT or MRI is done to exclude hemorrhage and confirm the presence and extent of stroke. Thrombolytic therapy may be useful acutely in certain patients. Depending on the cause of stroke, carotid endarterectomy or stenting, antiplatelet drugs, or warfarin may help reduce risk of subsequent strokes.General stroke treatmentsAcute antihypertensive therapy only in certain circumstancesAntiplatelet therapyFor acute treatment, sometimes reperfusion with recombinant tissue plasminogen activator (IV or thrombolysis-in-situ), and/or mechanical thrombectomySometimes anticoagulationLong-term control of risk factorsSometimes carotid endarterectomy or stentingAcute stroke treatmentGuidelines for early management of stroke are available from the American Heart Association and American Stroke Association. Patients with acute ischemic strokes are usually hospitalized. Supportive measures may be needed during initial evaluation and stabilization.

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Perfusion of an ischemic brain area may require a high BP because autoregulation is lost; thus, BP should not be decreased except in the following cases:BP is > 220 mm Hg systolic or > 120 mm Hg diastolic on 2 successive readings > 15 min apart.There are signs of other end-organ damage (eg, aortic dissection, acute MI, pulmonary edema, hypertensive encephalopathy, retinal hemorrhages, acute renal failure).Use of recombinant tPA and/or mechanical thrombectomy is likely.To lower BP, clinicians can give nicardipine 2.5 mg/h IV initially; dose is increased by 2.5 mg/h q 5 min to a maximum of 15 mg/h as needed to decrease systolic BP by 10 to 15%. Alternatively, IV labetalol 20 mg IV can be given over 2 min; if response is inadequate, 40 to 80 mg can be given every 10 min up to a total dose of 300 mg.Patients with presumed thrombi or emboli may be treated with one or a combination of the following:tPA, thrombolysis-in-situ, and/or mechanical thrombectomy (1)Antiplatelet drugsAnticoagulantsMost patients are not candidates for thrombolytic therapy; they should be given an antiplatelet drug (usually aspirin 325 mg po) when they are admitted to the hospital. Contraindications to antiplatelet drugs include aspirin-induced or NSAID-induced asthma or urticaria, other hypersensitivity to aspirin or to tartrazine, acute GI bleeding, G6PD deficiency, and use of warfarin.

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Recombinant tPA can be used for patients with acute ischemic stroke up to 3 h after symptom onset if they have no contraindications to tPA (see Table: Exclusion Criteria for Use of Tissue Plasminogen Activator in Stroke). Some experts recommend using tPA up to 4.5 h after symptom onset (see Expansion of the Time Window for Treatment of Acute Ischemic Stroke With Intravenous Tissue Plasminogen Activator); however, between 3 h and 4.5 h after symptom onset, additional exclusion criteria apply (see Table: Exclusion Criteria for Use of Tissue Plasminogen Activator in Stroke). Although tPA can cause fatal or other symptomatic brain hemorrhage, patients treated with tPA strictly according to protocols still have a higher likelihood of functional neurologic recovery. Only physicians experienced in stroke management should use tPA to treat patients with acute stroke; inexperienced physicians are more likely to violate protocols, resulting in more brain hemorrhages and deaths. When tPA is given incorrectly (eg, when given despite the presence of exclusion criteria), risk of hemorrhage due to tPA is high mainly for patients who have had stroke; risk of brain hemorrhage is very low (about 0.5%; 95% confidence interval of 0 to 2.0% [2]) for patients who have had a stroke mimic. If experienced physicians are not available on site, consultation with an expert at a stroke center (including video evaluation of the patient [telemedicine]), if possible, may enable these physicians to use tPA. Because most poor outcomes result from failure to strictly adhere to the protocol, a checklist of inclusion and exclusion criteria should be used.

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Exclusion Criteria for Use of Tissue Plasminogen Activator in Stroke iconThrombolysis-in-situ (angiographically directed intra-arterial thrombolysis) of a thrombus or embolus can sometimes be used for major strokes if symptoms began < 6 h ago, particularly for strokes that are due to large occlusions in the middle cerebral artery and cannot be treated with IV recombinant tPA. Clots in the basilar artery may be intra-arterially lysed up to 12 h after stroke onset, sometimes even later depending on the clinical circumstances. This treatment, although standard of care in some large stroke centers, is often unavailable in other hospitals.Mechanical thrombectomy (angiographically directed intra-arterial removal of a thrombus or embolus by a stent retriever device) is often used to treat patients who have had a severe stroke and have an NIH stroke score ≥ 6 when IV and/or intra-arterial thrombolysis has been ineffective; it must be done within 6 h of symptom onset (1). Mechanical thrombectomy may be part of standard of care in large stroke centers. It should not be used outside of a stroke center and should not be used instead of IV recombinant tPA within 4.5 h of onset of symptoms in eligible patients with acute ischemic stroke. Devices used to remove thrombi are being improved, and recent models reestablish perfusion in 90 to 100% of patients. It is unclear whether clinical outcomes are better after successful mechanical reperfusion than after treatment with IV tPA; evidence suggests that the earlier reperfusion is achieved, the better the outcome regardless how it is achieved.

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In some stroke centers, IV tPA, thrombolysis in situ, and/or mechanical thrombectomy are sometimes done based on imaging criteria (tissue-based criteria) rather than on time after symptom onset (time-based criteria). Tissue-based criteria can be used when time of symptom onset cannot be established (eg, if a patient awakens with stroke symptoms after sleeping several hours or if a patient has aphasia and cannot provide a time frame). To determine eligibility, clinicians use imaging to identify potentially salvageable brain tissue (also called penumbral tissue). The volume of infarcted tissue identified by diffusion-weighted MRI is compared with the volume of at-risk underperfused tissue identified by perfusion-weighted MRI or CT. A sizeable mismatch between the volumes identified by diffusion-weighted and perfusion-weighted imaging suggests that substantial penumbral tissue may still be rescued, and thus thrombolysis and/or thrombectomy is indicated. However, time-based criteria are still used in clinical practice; studies to determine whether outcomes are better using tissue- or time-based criteria are ongoing.

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tPA must be given within 4.5 h of symptom onset—a difficult requirement. Because the precise time of symptom onset may not be known, clinicians must start timing from the moment the patient was last observed to be well.Before treatment with tPA, the following are required:Brain hemorrhage must be excluded by CT.Systolic BP must be < 185 mm Hg.Diastolic BP must be < 110 mm Hg.Antihypertensive drugs (IV nicardipine, IV labetalol) may be given as above.Dose of tPA is 0.9 mg/kg IV (maximum dose 90 mg); 10% is given by rapid IV injection, and the remainder by constant infusion over 60 min. Vital signs are closely monitored for 24 h after treatment, and BP is maintained below 185 mm Hg systolic and 110 mm Hg diastolic. Any bleeding complications are aggressively managed. Anticoagulants and antiplatelet drugs are not used within 24 h of treatment with tPA.TABLE

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Anticoagulation with heparin or low molecular weight heparin is used for stroke caused by cerebral venous thrombosis and is sometimes used for emboli due to atrial fibrillation and for stroke due to presumed progressive thrombosis if it continues to evolve despite use of antiplatelet drugs and cannot be treated any other way (eg, with tPA or invasive methods). In one large series, outcomes after treatment of basilar artery thrombosis with IV heparin plus IV tPA were as good as or better than those after treatment with endovascular therapies. Warfarin is begun simultaneously with heparin. Before anticoagulation, hemorrhage must be excluded by CT. Constant weight-based heparin infusion (see Figure: Weight-based heparin dosing) is used to increase PTT to 1.5 to 2 times baseline values until warfarin has increased the INR to 2 to 3 (3 in hypercoagulable disorders). Because warfarin predisposes to bleeding and is continued after hospital discharge, its use should be restricted to patients who are likely to comply with dosage and monitoring requirements and who are not prone to falls.Long-term stroke treatmentSupportive care is continued during convalescence. Controlling hyperglycemia and fever can limit brain damage after stroke, leading to better functional outcomes.

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Long-term management also focuses on prevention of recurrent stroke (secondary prevention). Modifiable risk factors (eg, hypertension, diabetes, smoking, alcoholism, dyslipidemia, obesity) are treated. Reducing systolic BP may be more effective when the target BP is < 120 mm Hg rather than the typical level (< 140 mm Hg).Extracranial carotid endarterectomy or stenting is indicated for patients with recent nondisabling, submaximal stroke attributed to an ipsilateral carotid obstruction of 70 to 99% of the arterial lumen or to an ulcerated plaque if life expectancy is at least 5 yr. In other symptomatic patients (eg, patients with TIAs), endarterectomy or stenting with antiplatelet therapy is indicated for carotid obstruction of ≥ 60% with or without ulceration if life expectancy is at least 5 yr. These procedures should be done by surgeons and interventionists who have a successful record with the procedure (ie, morbidity and mortality rate of < 3%) in the hospital where it will be done. If carotid stenosis is asymptomatic, endarterectomy or stenting is beneficial only when done by very experienced surgeons or interventionists, and that benefit is likely to be small. For many patients, carotid stenting with an emboli-protection device (a type of filter) is preferred to endarterectomy, particularly if patients are < 70 yr and have a high surgical risk. Carotid endarterectomy and stenting are equally effective for stroke prevention. In the periprocedural period, MI is more likely after endarterectomy, and recurrent stroke is more likely after stenting.Extracranial vertebral angioplasty and/or stenting can be used in certain patients with recurrent symptoms of vertebrobasilar ischemia despite optimal medical treatment and a vertebral artery obstruction of 50 to 99%.Intracranial major artery angioplasty and/or stenting is considered investigational for patients with recurrent stroke or TIA symptoms despite optimal medical treatment and a 50 to 99% obstruction of a major intracranial artery.Endovascular closure of a patent foramen ovale does not appear to be more effective for preventing strokes than medical management, but studies are ongoing.Oral antiplatelet drugs are used to prevent subsequent noncardioembolic (atherothrombotic, lacunar, cryptogenic) strokes (secondary prevention). The following may be used:Aspirin 81 or 325 mg once/dayClopidogrel 75 mg once/dayThe combination product aspirin 25 mg/extended-release dipyridamole 200 mg bidIn patients taking warfarin, antiplatelet drugs additively increase risk of bleeding and are thus usually avoided; however, aspirin is occasionally used simultaneously with warfarin in certain high-risk patients. Clopidogrel is indicated for patients who are allergic to aspirin. If ischemic stroke recurs or if a coronary artery stent becomes blocked while patients are taking clopidogrel, clinicians should suspect impaired metabolism of clopidogrel (ineffective conversion of clopidogrel to its active form because CYP2C19 activity is reduced); a test to determine CYP2C19 status (eg, genetic testing for CYP450 polymorphisms) is recommended. If impaired metabolism is confirmed, aspirin or the combination product aspirin/extended-release dipyridamole is a reasonable alternative.If patients have had a TIA or minor stroke, clopidogrel plus aspirin given within 24 h of symptom onset appears more effective than aspirin alone for reducing risk of stroke in the first 90 days and does not increase risk of hemorrhage. However, prolonged (eg, > 6 mo) use of clopidogrel plus aspirin is avoided because it has no advantage over aspirin alone in long-term secondary stroke prevention and results in more bleeding complications. Clopidogrel plus aspirin before and for ≥ 30 days after stenting is indicated, usually for ≤ 6 mo; if patients cannot tolerate clopidogrel, ticlopidine 250 mg bid can be substituted.Oral anticoagulants are indicated for secondary prevention of cardioembolic strokes (as well as primary prevention). Adjusted-dose warfarin (a vitamin K antagonist) with a target INR of 2 to 3 is used for certain patients with nonvalvular or valvular atrial fibrillation. A target INR of 2.5 to 3.5 is used if patients have a mechanical prosthetic cardiac valve. Efficacious alternatives to warfarin for patients with nonvalvular atrial fibrillation include the following new anticoagulants:Dabigatran (a direct thrombin inhibitor) 150 mg bid in patients without severe renal failure (creatinine clearance < 15 mL/min) and/or liver failure (elevated INR)Apixaban (a direct factor Xa inhibitor) 5 mg bid in patients ≥ 80 yr, in patients with serum creatinine ≥ 1.5 mg/dL and creatinine clearance ≥ 25 mL/min, or as an alternative to aspirin in patients who cannot take warfarinRivaroxaban (a direct factor Xa inhibitor) 20 mg once/day for patients without severe renal failure (creatinine clearance < 15 mL/min)The main advantage of these new anticoagulants is ease of use (eg, no need to check anticoagulation level with a blood test after the initial dose or to use a parenteral anticoagulant such as unfractionated heparin given by continuous infusion when transitioning from parenteral to oral anticoagulants). Their main disadvantage is lack of an antidote to reverse anticoagulation in case a hemorrhagic complication occurs; the exception is dabigatran, for which idarucizumab is an antidote (4). Efficacy and safety of combining any of these new anticoagulants with an antiplatelet drug have not been established.Statins are used to prevent recurrent strokes; lipid levels must be decreased by substantial amounts. Atorvastatin 80 mg once/day is recommended for patients with evidence of atherosclerotic stroke and LDL (low-density lipoprotein) cholesterol ≥ 100 mg/dL. A reasonable LDL cholesterol target is a 50% reduction or a level of < 70 mg/dL. Other statins (eg, simvastatin, pravastatin) may be also used.

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72. Recognized indications for warfarin therapy include

Intermittent AF

MS with sinus rhythm

AF with a TIA

AF with HT and DM

Primary pulmonary hypertension

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Venous ThrombosisProphylaxis and treatment of venous thrombosis and its extension, pulmonary embolism (PE)DVT and PE treatmentDVT/PE and active cancer: Extended treatment,

Prevention of venous thromboembolism for total knee arthroplasty, total hip arthroplasty, and hip fracture surgery: Minimum treatment duration of 10-14 days, with a recommendation to extend outpatient therapy to 35 days (ACCP recommends LMWH over vitamin K antagonist therapy)

Stroke & ThromboembolismProphylaxis and treatment of systemic embolic complications (eg, stroke) associated with atrial fibrillation (AF)ACCP guidelines recommend dabigatran 150 PO BID over adjusted-dose warfarin therapy for AF unless botmgh AF and mitral stenosis are presentINR range and treatment durationNonvalvular AF: Maintain an INR of 2.0-3.0AF and stable CAD: Adjusted-dose warfarin therapy (INR 2.0-3.0) without aspirinAF with high stroke risk and placement of stent: Triple therapy of dose-adjusted warfarin (INR 2.0-3.0), clopidogrel, and aspirin; for 1 month if bare metal stent; for 3-6 months for drug-eluting stentAF with intermediate to high stroke risk without stent placement: 12 months of warfarin therapy (INR 2.0-3.0) with single antiplatelet regimenAF for more than 48 hours to undergo cardioversion: Warfarin therapy (INR 2.0-3.0) for 3 weeks prior to and 4 weeks after cardioversionIndications for indefinite treatment durationPersistent or paroxysmal nonvalvular AF in patients with a high risk of stroke: Ie, patients who have risk factors for stroke, such as prior ischemic stroke, transient ischemic attack, or systemic embolism or who have 2 of the following risk factors--age greater than 75 years, moderately or severely impaired left ventricular systolic function and/or heart failure, history of hypertension, or diabetes mellitusPersistent or paroxysmal nonvalvular AF in patients with an intermediate risk of ischemic stroke: Ie, patients who have 1 of the following risk factors--age >75 years, moderately or severely impaired left ventricular systolic function and/or heart failure, history of hypertension, or diabetes mellitusAF and mitral stenosis≥2 episodes of documented DVT or PECardiac Valve ReplacementProphylaxis and treatment of thromboembolic complications associated with cardiac valve replacementPost-Myocardial InfarctionReduction in the risk of death, recurrent MI, and thromboembolic events (eg, stroke, systemic embolization) after MI

Rheumatic valve disease with any of the following: Atrial diameter >55 mm, left atrial thrombus, atrial fibrillation, and previous systemic embolismSystolic LV Dysfunction (Off-label)Systolic LV dysfunction without established CAD but with identified acute LV thrombus (eg, Takotsubo cardiomyopathy)Antiphospholipid Antibody Syndrome (Off-label)Antiphospholipid antibody syndrome with previous arterial or venous thromboembolism

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Individualized doses and monitoring of PT/INR are necessaryMonitoring frequency should be daily or once every few days until stabilized; once stable, q4-6 weeks or longer may be appropriate (eg, 12 weeks)Not all factors causing warfarin dose variability are known, but they include age, race, sex, body weight, concomitant medications, and comorbidities, in addition to genetic factorsLower starting doses (ie, 2-5 mg/day × 2 days) recommended with the elderly, hepatic impairment, poor nutrition, CHF, high bleeding risk, debilitated patients, heart valve replacement, concomitant medications known to increase warfarin effect, or individuals suspected of having genomic variantsPerioperative management recommendations: Hold warfarin therapy approximately 5 days before surgery; resume warfarin 12-24 hr after surgery; bridge anticoagulation during interruption in patients at high thromboembolism riskMinor procedures and dental procedures: See ACCP guidelines for specific recommendations

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Warfarin has no direct effect on an established thrombus, nor does it reverse ischemic tissue damageSystemic atheroemboli and cholesterol microemboli; some cases have progressed to necrosis or death; discontinue therapy if such emboli occurPregnant women with mechanical heart valves: Therapy may cause fetal harm; however, benefits may outweigh the risksDosage ModificationsHepatic impairment: May potentiate warfarin response because of decreased metabolism and impaired synthesis of clotting factors

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Q

Treatments known to prolong survival in heart failure include

Metoprolol

Epleronone

AICDCardiac resynchronization therapy

Cardiac transplant

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Eplerenone is in a class of medications called mineralocorticoid receptor antagonists. It works by blocking the action of aldosterone, a natural substance in the body that raises blood pressure.

⏳BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is associated with increased risk for hospitalization and all-cause mortality. Currently, there is no established treatment to improve the survival of these patients. Aldosterone appears to play a role in the pathogenesis of HFpEF.

Conclusion: This study suggests there is no significant difference in mortality or cardiac hospitalisation between CRT-D and CRT-P in elderly patients with heart failure.

💞

Heart transplantation has a high early mortality—15-20% of recipients die within a year of the operation.2,3 Thereafter the death rate is constant, at about 4% a year for the next 18 years, so that 50% of patients can expect to be alive after 10 years and 15% after 20 years.

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American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society) guidelines recommend implantable cardioverter-defibrillator (ICD) therapy primary prevention in all patients with severely reduced left ventricular ejection fraction (≤30%) regardless of New York Heart Association (NYHA) functional class, whereas recent European guidelines limit the indication to those with symptomatic heart failure (NYHA ≥ II)

💝💘💗

conclusion, primary ICD therapy provides consistent long-term survival benefit among patients with previous myocardial infarction and severe left ventricular dysfunction, regardless of HF symptoms.

💟💔

CONCLUSIONS: Data from this nonrandomized study indicate that CRT-D has additional survival benefits over CRT-P. Given these findings, CRT-D should be recommended to most CHF patients with indications for biventricular pacing.

After CRT implant, chronic renal failure, diabetes mellitus, and history of atrial fibrillation are strong independent predictors of death

A predicted 30% worsening of heart failure was reduced in reality to 21%. In patients undergoing cardiac resynchronization therapy there were reductions in mortality (23%), hospitalizations (13%), and worsening of heart failure (26%).

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Q

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Q

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Q

.T/F regarding coronary artery disease prevention

Goal LDL cholesterol level for secondary prevention is <130mg/dl

Goal LDL level for primary CAD prevention in diabetics is <160mg/dl

Goal BP for diabetics is 140/90

Goal LDL for primary CAD prevention in a hypertensive and a smoker is<130mg/dl

Statin therapy is beneficial immediate post MI irrespective of the cholesterol level

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What

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69. Drugs used in the primary prevention of CAD include

Aspirin

Statin

Beta blockers

Clopidogrel

Nitrates

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The prevention of coronary artery disease (CHD) and particularly of myocardial infarction (MI) is based on some well designed strategies aimed at treating both

asymptomatic high-risk patients (primary prevention) and

patients with established CHD (secondary prevention).

A positive impact from primary prevention can be basically achieved trough a reduction in high blood pressure and by correcting dyslipidemia.

The benefit can be substantially increased by smoking cessation, increasing physical exercise, reduction of body weight, use of post-menopausal oestrogen, moderate alcohol consumption and use of high doses of vitamin E n those patients who are compliant with the specific strategies.

Secondary prevention of MI can be again obtained by controlling blood pressure and reducing serum cholesterol in patients surviving acute MI who can also benefit from the administration of beta-blockers, aspirin and probably ace-inhibitors particularly in presence of left ventricular dysfunction.

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70. Drugs known to prolong survival in heart failure includeNitrates with hydralazineDigoxinACEIARBSIvabradin

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Q

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CVD is now the leading cause of death globally as well.

The most preventable form of CVD is coronary heart disease (CHD).

. Treatment with multiple therapies (statins, angiotensin converting enzyme [ACE] inhibitor/angiotensin receptor blockers [ARBs], and aspirin) is associated with reduced all-cause mortality.

Secondary prevention relies on early detection of disease process and application of interventions to prevent progression of disease (MeSH definition).

Risk Assessment and Primary Prevention

Risk factors and risk scoresPrimary prevention reduces the risk of myocardial infarction (MI) and heart failure, decreases the need for coronary revascularization procedures, and extends and improves quality of life.

In their 2013 guidelines, the American College of Cardiology (ACC) and the American Heart Association (AHA) devised a new score to estimate the 10-year risk of developing a first atherosclerotic cardiovascular disease (ASCVD) event, which was defined as nonfatal MI, coronary heart disease (CHD) death, or fatal or nonfatal stroke, over a 10-year period, in individuals who were initially free from ASCVD. [11, 12]The new score provides sex- and race-specific estimates for the first ASCVD event for black and white men and women aged 40-79 years.

Variables that merit inclusion in the risk assessment equations are age, total cholesterol, high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP) (including treated or untreated status), diabetes mellitus (diabetes), and current smoking status.The ASCVD Risk Estimator is available at: http://tools.acc.org/ASCVD-Risk-Estimator/. [11, 12]The recommendations for assessment of the 10-year risk for a first hard ASCVD event are as follows [11, 12] :Non-Hispanic black and non-Hispanic white individuals aged 40-79 years: The race- and sex-specific Pooled Cohort Equations to predict 10-year risk for a first hard ASCVD event should be used. Patients from populations other than black and non-Hispanic white groups: Use of the sex-specific Pooled Cohort Equations for non-Hispanic white individuals may be considered. Updated guidelines advantagesThe ACC/AHA indicate that two major advantages of these guidelines are the ability to not only estimate the risk for a broader-based ASCVD outcome that is more relevant to population groups (eg, women, black individuals) but also to provide risk estimates that are specific to black populations. [11, 12]Screening guidelinesIn 2015, the American College of Physicians (ACP) released guidelines on screening for CHD, including the following [13] :There is no evidence that cardiac screening improves patient outcomes in asymptomatic, low-risk adults.Potential harms of cardiac screening include false-positive results causing patients to undergo potentially unnecessary tests and procedures.Among adults at low risk, prevalence of CHD is low, and cardiac screening is of low predictive value. Therefore, cardiac screening is of low yield, and the probability that positive findings will influence therapeutic decision making is low.Clinicians should therefore emphasize strategies to reduce cardiovascular risk even further among low-risk adults by treating modifiable risk factors (smoking, diabetes, blood pressure [BP], hyperlipidemia, overweight, and exercise).Clinicians should not screen asymptomatic, low-risk adults for cardiac disease using resting or stress electrocardiography (ECG), stress echocardiography, or stress myocardial perfusion imaging.Clinicians should conduct cardiovascular risk assessment with a global risk score combining individual risk factor measurements into a single quantitative estimate of risk.The ACP recommendations do not apply to symptomatic patients or to screening athletes before participation in various events.The 2013 ACC/AHA guidelines indicate that for patients aged 20-79 years who do not have existing clinical ASCVD, assess for clinical risk factors every 4-6 years. [11, 12] For patients with low 10-year risk (< 7.5%), the guidelines recommend assessing 30-year or lifetime risk in patients aged 20-59 years.Regardless of the patient’s age, clinicians should communicate risk data to the patient and refer to the AHA/ACC lifestyle guidelines, which cover diet and physical activity. [14, 15] For patients with an elevated 10-year risk, clinicians should communicate risk data and refer to the AHA/ACC guidelines on blood cholesterol and obesity. [16, 17]Hypercholesterolemia/dyslipidemiaThe 2013 AHA/ACC guidelines on the management of elevated blood cholesterol no longer specify low-density lipoprotein (LDL-C) and non-HDL-C targets for the primary and secondary prevention of atherosclerotic CVD. The new guidelines identify four groups of primary- and secondary-prevention patients in whom efforts should be focused to reduce cardiovascular disease events and recommend appropriate levels of statin therapy for these groups. [11, 16, 17]Four statin-benefit groupsThe 2013 AHA/ACC guidelines indicate that statin therapy is appropriate for the following individuals [16, 17, 18] :Those with clinical ASCVD (eg, previous MI, acute coronary syndrome [ACS], stable or unstable angina, stroke, transient ischemic attack [TIA] of atherosclerotic origin, peripheral arterial disease)Those with primary elevations of LDL-C of 190 mg/dL or greater (eg, familial hyperlipidemia)Those aged 40-75 years with diabetes and LDL-C levels of 70-89 mg/dL without clinical ASCVDThose without clinical ASCVD or diabetes aged 40-75 years who have LDL-C levels of 70-189 mg/dL as well as an estimated 10-year ASCVD risk of 7.5% or higher. This requires a clinician-patient discussion.Initiation of statin therapyBefore therapy is initiated, the following potential secondary causes of dyslipidemia should be considered based on the associated dyslipidemia:High LDL: Hypothyroidism, [19, 20] nephrotic syndrome, primary biliary cirrhosis, [21] and anorexia nervosa [22, 23]Hypertriglyceridemia (triglyceride levels ≥500 mg/dL [5.65 mmol/L]) [18] : Diabetes mellitus, [24] chronic kidney disease, alcoholism, pregnancy, [25] hypothyroidism [19, 20]Low HDL: Diabetes mellitus, cigarette smoking, [26, 27] obesity [28]The AHA/ACC expert panel found extensive and consistent evidence supporting the use of statins for the prevention of ASCVD in many higher-risk primary- and all secondary-prevention individuals [16, 17] without New York Heart Association (NYHA) class II-IV heart failure who were not receiving hemodialysis. [18] In the randomized controlled trials (RCTs) reviewed, initiation of moderate-intensity therapy (lowering LDL-C by approximately 30% to < 50%) or high-intensity statin therapy (lowering LDL-C by approximately ≥50%) is a critical factor in reducing ASCVD events. [16, 17, 18] Moreover, statin therapy reduces ASCVD events across the spectrum of baseline LDL-C levels of 70 mg/dL or higher. In addition, the relative reduction in ASCVD risk is consistent for primary and secondary prevention and for various patient subgroups. [16, 17, 18]Of note, the absolute reduction in ASCVD events is proportional to baseline absolute ASCVD risk. Therefore, statin therapy is recommended for individuals at increased ASCVD risk who are most likely to experience a net benefit in terms of the potential for ASCVD risk reduction and the potential for adverse effects. [16, 17, 18]Statin intensity recommendations in appropriate patientsHigh-intensity statin therapy (lowers LDL-C by approximately ≥50%) [16, 17, 18] :Atorvastatin 40-80 mgRosuvastatin 20-40 mgModerate-intensity statin therapy (lowers LDL-C by approximately 30% to < 50%) [16, 17, 18] :Atorvastatin 10-20 mgRosuvastatin 5-10 mgSimvastatin 20-40 mgPravastatin 40-80 mgLovastatin 40 mgFluvastatin XL 80 mgFluvastatin 40 mg twice dailyPitavastatin 2-4 mgLow-intensity statin therapy (lowers LDL-C by approximately < 30%) [16, 17, 18] :Simvastatin 10 mgPravastatin 10-20 mgLovastatin 20 mgFluvastatin 20-40 mgPitavastatin 1 mgPrimary prevention recommendationsIn considering statin therapy—for all patients, regardless of whether or not they fall into the statin-benefit groups—always keep in mind and discuss the potential clinical ASCVD risk-reduction benefits, adverse events, drug-drug interactions, and patient preferences. [16, 17, 18]Adults aged 21 years and older with LDL-C levels of 190 mg/dL or greater [16, 17, 18] :Evaluate for secondary causes of hyperlipidemia (discussed above).Treat with statins (high-intensity agents, unless contraindicated; otherwise to maximum tolerated intensity).Untreated patients: Intensify statin therapy to achieve a minimum 50% LDL-C reduction; once the maximum intensity of statin therapy is achieved, add a non-statin agent for further LDL-C reduction.Diabetic adults aged 40-75 years with LDL-C levels of 70-189 mg/dL (1.81-4.90 mmol/L) [16, 17, 18] :Initiate/continue moderate-intensity statin therapy.If the estimated 10-year ASCVD risk is 7.5% or greater, treat with high-intensity statin therapy, unless contraindicated.Nondiabetic adults aged 40-75 years without clinical ASCVD but have LDL-C levels of 70-189 mg/dL (1.81-4.90 mmol/L) [16, 17, 18] :Use the Pooled Cohort Risk Calculator to estimate the 10-year ASCVD risk and guide initiation of statins (see http://my.americanheart.org/cvriskcalculator or http://www.cardiosource.org/science-and-quality/practice-guidelines-and-quality-standards/2013-prevention-guideline-tools.aspx).If the estimated 10-year ASCVD risk is 7.5% or greater, treat with moderate- to high-intensity statin therapy.If the estimated 10-year ASCVD risk is 5% up to 7.5%, treat with moderate-intensity statin therapy.BP controlHypertension is a well-established risk factor for adverse cardiovascular outcomes, including CHD. SBP is at least as powerful a coronary risk factor as the diastolic BP (DBP). Isolated systolic hypertension has been established as a major hazard for CHD. Compelling data from meta-analyses indicate that a reduction of DBP by 5-6 mm Hg results in a reduction of stroke risk by 42% and CHD events by 15%. [29]The self-management of hypertension, which includes BP self-monitoring and self-titration of antihypertensive drugs, along with telemonitoring of home BP measurements, is an important addition to the control of hypertension in primary care. Patients who self-manage hypertension have experienced a decrease in SBP compared to those who sought usual care. [30] The Clinical Evaluation of Remote Notification to Reduce Time to Clinical Decision (CONNECT) trial found that wireless remote monitoring with automatic clinician alerts significantly reduced the time to a clinical decision in response to clinical events as well as reduced the length of hospital stay. [31]In patients with mild hypertension (SBP 140-159 mm Hg or DBP 90-99 mm Hg), the following is noted:Despite side effects and cost of antihypertensive medications, the beneficial effects of treatment may outweigh the risks, even in low-risk patients.Treatment, if necessary, is initiated with a low-dose of a once-a-day antihypertensive drug in an attempt to minimize future cardiovascular risk after a prolonged trial of nonpharmacologic therapy.One such antihypertensive medication that is used worldwide is hydrochlorothiazide (HCTZ). A daily dose of 12.5-25 mg was measured in head-to-head studies using ambulatory BP measurement (ABPM) and was shown to be consistently inferior to all other drug classes. Because data is lacking for dosing, HCTZ is an inappropriate first-line drug for the treatment of hypertension. [32]In individuals with high-normal BP (SBP 130-139 mm Hg and/or DBP 85-89 mm Hg), the following is noted:These persons have an increased risk of cardiovascular events over time compared with those who have optimal BP.Antihypertensive drug therapy should be considered among such patients if diabetes or end-organ damage is present.Treatment, particularly with an angiotensin-converting enzyme (ACE) inhibitor or, if not tolerated, an angiotensin-II receptor blocker (ARB), is also warranted in patients with renal insufficiency, diabetes mellitus, or heart failure to slow the progression of the underlying disease.AlcoholModerate alcohol consumption (1-2 drinks per day is associated with a reduced overall and CHD-related mortality compared with both abstinence and heavy drinking. [33, 34]However, alcohol raises HDL-C (by stimulating the hepatic production of apolipoprotein [apo] A-I and A-II), [35, 36, 37] stimulates fibrinolysis, [38, 39, 40] reduces fibrinogen levels, [41, 42] reduces inflammation, [43] and inhibits platelet activation. [44] Moreover, the personal and social risks of alcohol intake (eg, violence, trauma, car accidents, binge drinking) appear to be higher in younger individuals. [45]In the United States, additional antioxidant effects have been attributed to red wine, but the consumption of other alcoholic beverages is associated with a somewhat lower or similar reduction in CHD risk, [46, 47] and the pattern and amount of alcohol intake appears to be more important than the type.AntioxidantsAlthough several observational studies and 1 randomized, controlled secondary prevention trial (CHAOS) [48] found reduced CVD in those taking large amounts of antioxidant vitamins, no benefit for 400 and 300 IU/d of vitamin E, respectively, was found in the Heart Outcomes Prevention Evaluation (HOPE) [49] ​Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevention, [50] and Heart Protection Studies (HPS). [51]A meta-analysis of available data suggests no benefit for antioxidant vitamins. [52]HerbalsAn estimated 40% of the US population uses herbal remedies, and at least $15 billion is spent annually in North America on alternative forms of health care. Inquiry about the use of herbals is a component of good medical care, especially in cardiovascular medicine.Alternative medicine approaches to cholesterol lowering include garlic, policosanol, gugulipid, and red rice yeast extracts, the latter of which contains 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors. Garlic modestly lowers cholesterol (approximately 3%) and may lower BP and inhibit platelet aggregation. Fermented red rice yeast extracts contain statins and lower cholesterol 13-26%. [53] Ephedra-containing herbals, often used as anorexics, are associated with hypertension and stroke and have been banned in the United States. [54, 55]Aspirin no longer in favorTwo meta-analyses showed that aspirin use (75-162 mg/d) decreases the occurrence of primary MI by 25-33%, and it has also been shown to decrease death due to vascular causes; these benefits are not gender specific. [56, 57] However, all benefits have to be balanced against the risk of gastrointestinal bleeding. Previously aspirin use has been recommended for primary prevention of CVD and colorectal cancer. Clinicians were advised to initiate low-dose aspirin for individuals aged 50-59 years who have the following features (grade B recommendation) [58] :Have a 10-year ASCVD risk 10% or greaterAre not at increased bleeding riskHave a life expectancy of 10 years or longerAre willing to take daily low-dose aspirin for at least 10 years In addition, it was advised that treatment be individualized for individuals aged of 60-69 years with a 10-year ASCVD risk of 10% or greater (grade C recommendation). The use of aspirin was thought likely to benefit this age group who share the features of those listed in the 50-59 years age population. [58] Those who placed a higher value on the potential benefits than the potential harms could choose to initiate low dose aspirin. For adults younger than 50 years or older than 70 years, there was insufficient evidence evaluate the benefits/risks of initiating low-dose aspirin. [58]More recent trials indicate that aspirin has no role in primary prevention of cardiovascular events. Some studies found no effect of aspirin on cardiovascular risk reduction in long-term primary prevention, whereas others demonstrated the risks of aspirin use outweighed its benefits. [59, 60, 61, 62]In 2018, three large trials released their findings regarding the use of aspirin for primary prevention in different patient populations. The A spirin to R educe R isk of I nitial V ascular E vents (ARRIVE) trial (N = 12,546) showed aspirin had no effect on all-cause death or cardiovascular outcome in patients with moderate cardiovascular risk. [59] The A S tudy of C ardiovascular E vents in D iabetes (ASCEND) (N = 15,480) found a modest benefit in reducing cardiovascular in patients with diabetes, but there was a relatively significant increased risk of major hemorrhage. [60] The Asp irin in R educing E vents in the E lderly (ASPREE) trial (N = 19,114) revealed that not only did aspirin have no effect on the primary outcome (death, dementia, disability) in elderly patients, but it led to a higher rate of major hemorrhage and the all-cause mortality was actually greater in the group taking aspirin than that of the placebo group. [61, 62] This unexpected finding of higher mortality was primarily atrributed to cancer-related death, which occurred in 3.1% of the aspirin users and in 2.3% of those in the placebo group. [62]A 2019 systematic review and meta-analysis of data from 13 trials comprising 164,225 individuals without cardiovascular disease to evaluate the association between aspirin use and cardiovascular and bleeding events found a lower risk of cardiovascular events and a higher risk of major bleeding. [63]Lifestyle ManagementPrimary prevention should start with lifestyle modification, including smoking cessation, weight management, diet, and physical activity. Hormone therapy increases cardiovascular events in postmenopausal women. Estrogen alone increases stroke, but it does not alter coronary heart disease (CHD) events.Smoking cessationOf all the lifestyle modifications recommended to prevent cardiovascular disease (CVD), smoking cessation is the most important. Tobacco use prematurely kills more than 480,000 Americans annually. [64] Smoking cessation is the most cost-effective preventive measure, estimated at $220 to $5050 per year of life saved (LYS) in 1993 to $490 to $15,280 LYS in 2006. [65] Individuals aged 30 years gain 3-5 years of life by stopping smoking, and the mortality benefit was shown to be equally impressive in elderly populations. [66, 67] The most effective smoking cessation programs involve programmatic and/or group support and the use of nicotine substitutes and antidepressants, such as bupropion. Varenicline is a more recent addition to the smoking cessation armamentarium and has been found to be superior to bupropion in this respect. [68, 69, 70]Smoking is a risk factor for CVD in women and men; however, a systemic review and meta-analysis by Huxley and Woodward suggested that in some countries, smoking by women has risen; the study suggested that proper counseling and nicotine addiction programs should focus on young women. [71]Smoking cessation counseling with supportive contact after a patient with acute myocardial infarction is discharged is potentially cost-effective and may reduce the incidence of smoking and further adverse health events. [72]The goal is complete cessation and no exposure to environmental tobacco smoke. The following "5 A's" are a common approach to assess patients' smoking behavior [73] :Ask the patient about tobacco use status at every visit.Advise every patient who uses tobacco to quit.Assess the patient’s willingness to quit using tobaccoAssist the patient by counseling and developing a plan for quitting.Arrange follow-up, referral to special programs, or pharmacotherapy (including nicotine replacement and bupropion).In addition, urge the patient to avoid exposure to environmental tobacco smoke at work and home.DietDietary recommendations from the 2013 American Heart Association (AHA)/American College of Cardiology (ACC) guideline on lifestyle management to reduce cardiovascular are summarized below. [14]Adults who would benefit from a reduction in LDL-CAdults who fall into this group should emphasize intake of foods including vegetables, fruits, whole grains, legumes, low-fat diary products, poultry, fish and nontropical vegetable oils. Limit the intake of sweets, sugar-sweetened beverages, and red meats. Adults can achieve this type of diet by following plans such as the DASH (Dietary Approaches to Stop Hypertension) diet (see below), AHA diet, or US Department of Agriculture (USDA) food patterns. (Level of evidence [LOE]: A)In addition, limiting the amount of calories from saturated fat to 5%-6% as well as reducing the percentage of calories from trans fat are recommended. (LOE: A)Adults who would benefit from reduction in blood pressure (BP)Adults who fall into this group should follow the same dietary emphasis as those who would benefit from LDL-C reduction (eg, vegetables, fruits, whole grains, legumes, DASH diet), as well as combine the DASH diet with a reduction in sodium intake. (LOE: A) Guidance in reducing sodium intake include not consuming more than 2,400 mg of sodium daily; an associated greater reduction in BP with further reduction to 1500 mg/day; and achieving a lower BP with reduction of sodium intake by at least 1000 mg daily. (LOE: B)DASH dietary patternThe DASH dietary pattern is high in vegetables, fruits, whole grains, low-fat/fat-free dairy products, poultry, fish, beans, nuts, and nontropical vegetable oils, as well as rich in potassium, magnesium, calcium, protein, and fiber. [14, 15, 74] It is low in sweets, sugar-sweetened beverages, sodium, and red meats, as well as saturated fat, total fat, and cholesterol. This dietary pattern aims for a daily maximum target of 2,000 calories.Compared to a typical American diet of the 1990s, the DASH dietary pattern reduced the following [14, 15] :BP by 5-6/3 mm Hg in adults with BP 120-159/80-95 mm Hg, for both women and men, black and non-black adults, older and younger adults, and hypertensive and nonhypertensive adultsLDL-C by 11 mg/dL and HDL-C by 4 mg/dL, with no effect on triglycerides, in adults with total cholesterol levels below 260 mg/dL and LDL-C levels below 160 mg/dL, including black and non-black adults, as well as hypertensive and non-hypertensive adultsAlcohol intakeLight-to-moderate alcohol consumption (5-25 g/d) has been significantly associated with a lower incidence of cardiovascular and all-cause mortality in patients with CVD. [75] A meta-analysis by Costanzo et al found J-shaped curves for alcohol consumption and mortality, with a significant maximal protection against cardiovascular mortality with consumption of approximately 26 g/d and maximal protection against mortality from any cause in the range of 5-10 g/d. [75]Physical activityReduced physical activity is a major risk factor for CVD. In elderly individuals, walking 30 minutes daily reduces the risk of MI by as much as 50%. [76, 77] The Cooper Center Longitudinal Study found that low fitness in mid-life was associated with a higher lifetime risk for CVD death, [78] and a study evaluating the relationship between physical activity and CVD risk among 44,551 men (age, 40-75 y) found that vigorous- and moderate-intensity activity were associated with a lower risk of CVD and major chronic disease. [79]The 2013 AHA/ACC lifestyle management guidelines recommendation for physical activity to reduce LDL-C, non HDL-C, and BP is 3-4 sessions each week that last an average of 40 minutes per session and involve moderate-to-vigorous intensity physical activity. [14]In 2018, the Physical Activity Guidelines Advisory Committee of the US Department of Health and Human Services (HHS) released their key recommendations, including the following [80, 81] :Regular physical activity minimizes excessive weight gain, helps maintain weight within a healthy range, improves bone health, and prevents obesity, even in children as young as 3-5 years.In pregnant women, physical activity helps reduce excessive weight gain in pregnancy and helps reduce the risk of developing gestational diabetes and postpartum depression.Regular physical activity has been shown to improve cognitive function and to reduce the risk of dementia; falls and fall-related injuries; and cancers of the breast, esophagus, colon, bladder, lung, endometrium, kidney, and stomach. It also helps retard the progression of osteoarthritis, type 2 diabetes, and hypertension.Adults: At least 150-300 minutes per week of moderate-intensity aerobic physical activity, OR 75-150 minutes per week of vigorous-intensity aerobic physical activity, OR an equivalent combination of moderate- and vigorous-intensity aerobic activity; muscle-strengthening activities should be performed on two or more days per week.Older adults: Multicomponent physical activity to include balance training, aerobic activity, and muscle-strengthening activity.Pregnant and postpartum women: At least 150 minutes of moderate-intensity aerobic activity weekly.Adults with chronic conditions or disabilities who are able: Follow key guidelines and perform both aerobic and muscle-strengthening activities. Abnormal heart rate recovery (HRR) has been demonstrated to be prognostic factor for mortality. [82] In attempting to determine whether HRR (defined as heart rate at peak exercise and exactly 1 minute into the recovery period) could be improved with cardiac rehabilitation, findings by Jolly et al suggest that patients with abnormal HRR at baseline could normalize HRR with exercise. The mortality rate of these patients was similar to that of individuals with baseline normal HRR. [82]The following general principles should be considered when recommending increased physical activity to patients:Increased physical activity begins with increasing lifestyle activities, such as walking.A complete exercise program includes stretching, aerobic exercise, and resistance training.More frequent exercise, optimally daily, provides more benefit.More strenuous exercise, such as jogging, provides more benefit. A good goal is 75% of the age-predicted maximal heart rate (220 – age of individual).Excellent benefit can be derived from 40 minutes of daily exercise.Studies have also shown that even 15 minutes daily or 90 minutes weekly of moderate-intensity exercise may be beneficial. [83]European studies suggest that increased waist circumference and physical inactivity are associated with an increased risk of CHD. [84]Weight managementThe goal of weight management is a body mass index (BMI) of 18.5-24.9 kg/m2 for men and women, as well as a waist circumference less than 40 inches in men and below 35 inches in women. [85] The 2011 AHA/ACCF (ACC Foundation) guideline for secondary prevention and risk reduction therapy for patients with CVD and other atherosclerotic vascular disease include the following weight management strategies [86, 87] :Assess BMI and/or waist circumference on each visit; consistently encourage weight maintenance/reduction with an appropriate balance of physical activity/structured exercise, caloric intake, and formal behavioral programs to maintain/achieve a BMI of 18.5-24.9 kg/m2.Measure horizontal waist circumference at the iliac crest; if it is at least 35 inches (≤89 cm) in women and at least 40 inches (≤102 cm) in men, intensify lifestyle changes, focusing on weight management.Aim for an initial weight-loss goal of about a 5%-10% reduction from baseline; when this goal is achieved, assess if further weight loss is indicated.The Aerobics Center Longitudinal Study found that maintaining or improving fitness was associated with a lower risk of all-cause and CVD mortality in men. [88] Healthcare providers should encourage men to exercise regularly, regardless of age and BMI change, as it is important for longevity. [88]Summary of general nutritional recommendationsAchieve and maintain ideal body weight by limiting foods high in calories and low in nutrition, including those high in sugar, (eg, soft drinks, candy).Eat a variety of fruits, vegetables, legumes, nuts, soy products, low-fat dairy products, and whole grain breads, cereals, and pastas.Consume baked/broiled fish at least twice per week.Choose oils and margarines low in saturated fat and high in omega-3 fat (eg, canola, soybean, walnut, and flaxseed oils, including those fortified with stanols and sterols).Avoid foods high in saturated and trans-fats (eg, red meat, whole milk products, pastries).Limit alcohol consumption to no more than 2 drinks daily for men or 1 drink daily for women.Take in less than 6 g of salt or less than 2400 mg/d of sodium.Secondary prevention (after development of CHD)Several large observational studies, all of which had at least 5 years of follow-up and a meta-analysis including these studies, showed a substantial reduction in mortality (relative risk [RR]: 0.64 (I: 0.58-0.71)] in patients with a history of MI, coronary artery bypass grafting (CABG), angioplasty, or known CHD, who quit smoking compared with patients who continued to smoke. [89, 90] The overall mortality risk of smokers who quit decreased by 50% in the first couple of years and had a tendency to approach that of nonsmokers in approximately 5-15 years of cessation of smoking.Secondary Prevention Goals and ManagementFor secondary prevention, individuals aged 75 years and younger with clinical atherosclerotic cardiovascular disease (ASCVD) should be started on high-intensity statin therapy unless contraindicated. [18] In individuals with clinical ASCVD with contraindications to high-intensity statin therapy but who would otherwise benefit from it, or in persons who are predisposed to statin-associated adverse effects, a second-line option is moderate-intensity statin therapy, if tolerated.When considering moderate- or high-intensity statin therapy in those older than 75 years with clinical ASCVD, assess the potential risk-reduction benefits, adverse effects, drug-drug interactions, and patient preferences. Continue statin therapy if tolerated. [18]Patients covered by current guidelines include those with established coronary and other atherosclerotic vascular disease, including peripheral arterial disease, atherosclerotic aortic disease, and carotid artery disease. Treatment for patients whose only manifestation of cardiovascular risk is diabetes will be the topic of a separate AHA scientific statement.The 2011 American Heart Association (AHA)/American College of Cardiology Foundation (ACCF) update of their guideline for secondary prevention and risk reduction therapy for patients with CVD and other atherosclerotic vascular disease can be found at: http://circ.ahajournals.org/content/124/22/2458.long. [86, 87] The recommendations are outlined below.Blood pressure controlThe goal is blood pressure (BP) below 140/90 mm Hg, or below 130/80 mm Hg if the patient has diabetes or chronic kidney disease. [86, 87]For all patients, initiate or maintain lifestyle modification, weight control, increased physical activity, alcohol moderation, sodium reduction, and increased consumption of fresh fruits, vegetables, and low-fat dairy products.For patients with BP of 140/90 mm Hg or greater (or ≥130/80 mm Hg for individuals with chronic kidney disease or diabetes), as tolerated, add BP medication, treating initially with beta-blockers and/or angiotensin-converting enzyme (ACE) inhibitors, with addition of other drugs, such as thiazides, as needed to achieve goal BP. [86, 87]See also the Medscape Drugs and Diseases topic Hypertension.Lipid managementThe goal is achieving low-density lipoprotein cholesterol (LDL-C) levels below 100 mg/dL; if triglyceride levels are 200 mg/dL or above, non-HDL-C (non-high-density lipoprotein cholesterol) levels should be below 130 mg/dL. (Non-HDL-C = total cholesterol – HDL-C.) [86, 87]The following measures should be taken for all patients [86, 87] :Start dietary therapy; reduce the intake of saturated fats (to < 7% of total calories), trans-fatty acids (< 7% of total calories), and cholesterol (to < 200 mg/dL).Adding plant stanols/sterols (2 g/d) and viscous fiber (>10 g/d) will further lower the LDL-C level.Promote daily physical activity and weight management.Encourage increased consumption of omega-3 fatty acids in the form of fish or in capsule form (1 g/d) for risk reduction. (Pregnant and lactating women should limit their intake of fish to minimize exposure to methylmercury.)For treatment of elevated triglyceride levels, higher doses are usually necessary for risk reduction.In addition, to encourage treatment compliance, particularly with cardiovascular medications in secondary prevention, clinicians should provide clear discussions about the risk of disease recurrence and medication-specific information at the start of pharmacotherapy, and they should ease the transition between primary and secondary care. [91]Assess fasting lipid profile in all patients and within 24 hours of hospitalization for those with an acute cardiovascular or coronary event. For hospitalized patients, before discharge, initiate lipid-lowering medication as recommended below, according to the following schedule [86, 87] :LDL-C level should be below 100 mg/dL, and further reduction of LDL-C level to less than 70 mg/dL is reasonable.If the baseline LDL-C level is 100 mg/dL, initiate LDL-C-lowering drug therapy.If the patient is on treatment and the LDL-C level is 100 mg/dL, intensify LDL-C-lowering drug therapy (may require LDL-C-lowering drug combination [standard dose of statin with ezetimibe, bile acid sequestrant, or niacin]).If the baseline LDL-C level is 70-100 mg/dL, treating to an LDL-C level below 70 mg/dL is reasonable.If the triglyceride levels are 200-499 mg/dL, non-HDL-C levels should be below 130 mg/dL, and further reduction of non-HDL-C levels to below 100 mg/dL is reasonable.Therapeutic options to reduce non-HDL-C level include the following [86, 87] :More intense LDL-C-lowering therapyNiacin (after LDL-C-lowering therapy)Fibrate therapy (after LDL-C-lowering therapy)If triglyceride levels are 500 mg/dL, fibrate or niacin is a therapeutic option to prevent pancreatitis before initiating LDL-C-lowering therapy. In addition, treat the LDL-C level to goal after triglyceride-lowering therapy. Achieve a non-HDL-C level below 130 mg/dL, if possible. Note the following [86, 87] :Patients with very high triglyceride levels should not consume alcohol.The use of bile acid sequestrants is relatively contraindicated when triglyceride levels are above 200 mg/dL.The risk for severe myopathy can be increased when the combination of a high-dose statin plus a fibrate is used. Therefore, maintain relatively low statin doses with this treatment combination.Do not substitute dietary supplement niacin for prescription niacin.In 2011, The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) stopped a clinical trial studying a blood lipid treatment that was adding high-dose, extended-release niacin to statin treatment in people with heart and vascular disease. [92] The study was stopped because the treatment did not reduce the risk of cardiovascular events, including heart attacks and stroke. The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes (AIM HIGH) study selected patients at risk for cardiovascular events despite well-controlled LDL-C. Participants who took high-dose, extended-release niacin and statin treatment had increased HDL-C and lower triglyceride levels compared to participants who took a statin alone. However, the combination treatment did not reduce fatal or nonfatal heart attacks, strokes, hospitalizations for acute coronary syndrome, or revascularization procedures to improve blood flow in the arteries of the heart and brain. [92]Furthermore, the AIM HIGH investigators concluded that patients with atherosclerotic CVD and LDL-C levels below 70 mg/dL (1.81 mmol/L) experienced no incremental clinical benefit from the addition of niacin to statin therapy, despite significant improvements in HDL-C and triglyceride levels. [93] AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guidelinesRecommendations on management of blood cholesterol were released in November 2018 by the AHA, ACC, and multiple other medical societies. [94, 95]The guideline's top 10 key recommendations for reducing the risk of atherosclerotic cardiovascular disease through cholesterol management are summarized below. [94, 95]Emphasize a heart-healthy lifestyle across the life course of all individuals.In patients with clinical atherosclerotic cardiovascular disease (ASCVD), reduce low-density lipoprotein cholesterol (LDL-C) levels with high-intensity statin therapy or the maximally tolerated statin therapy.In individuals with very high-risk ASCVD, use an LDL-C threshold of 70 mg/dL (1.8 mmol/L) to consider the addition of nonstatins to statin therapy.In patients with severe primary hypercholesterolemia (LDL-C level ≥190 mg/dL [≥4.9 mmol/L]), without calculating the 10-year ASCVD risk, begin high-intensity statin therapy.In patients 40 to 75 years of age with diabetes mellitus and an LDL-C level of ≥70 mg/dL: Start moderate-intensity statin therapy without calculating their 10-year ASCVD risk.In patients aged 40 to 75 years evaluated for primary ASCVD prevention: Have a clinician–patient risk discussion before starting statin therapy.Assess patient adherence and the percentage response to LDL-C–lowering medications and lifestyle changes with a repeat lipid measurement 4-12 weeks after initiation of statin therapy or dose adjustment; repeat every 3-12 months as needed.In nondiabetic patients aged 40 to 75 years and with the following characteristics [94, 95] :LDL-C levels ≥70 mg/dL (≥1.8 mmol/L), at a 10-year ASCVD risk of ≥7.5%: Start a moderate-intensity statin if a discussion of treatment options favors statin therapy.A 10-year risk of 7.5-19.9% (intermediate risk): Risk-enhancing factors favor initiation of statin therapy.LDL-C levels ≥70-189 mg/dL (≥1.8-4.9 mmol/L), at a 10-year ASCVD risk of ≥7.5-19.9%: If a decision about statin therapy is uncertain, consider measuring coronary artery calcium (CAC) levels. A study by Mills et al suggested that intensive statin dosing reduces the risk of nonfatal events (coronary heart disease and nonfatal myocardial infarction [MI]) and may have a role in reducing mortality. [96] However, the benefits of high-dose statins must be weighed against the risk of myopathy, including rhabdomyolysis, at high doses.When LDL-C-lowering medications are used, obtain at least a 30-40% reduction in LDL-C levels. If LDL-C below 70 mg/dL is the chosen target, consider drug titration to achieve this level to minimize side effects and cost. When the goal of LDL-C below 70 mg/dL is not achievable because of high baseline LDL-C levels, it generally is possible to achieve LDL-C reductions of over 50% by either statin therapy or LDL-C-lowering drug combinations.RVX-208, the first oral agent designed to enhance apolipoprotein (apo) A-I synthesis, has been shown to increase apoA-I, HDL-C, and concentrations of large HDL particles, as well as elevate liver enzymes. [97]Lowering LDL-C with statin regimens may have an effect in people with moderate-to-severe kidney disease. [98] The Study of Heart and Renal Protection (SHARP) trial suggests simvastatin (20 mg) plus ezetimibe (10 mg) daily safely reduces the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease.Secondary prevention trials in older persons with coronary artery disease and hypercholesterolemia have demonstrated that statin drugs reduced all-cause mortality, cardiovascular mortality, coronary events, coronary revascularization, stroke, and intermittent claudication. Statin therapy significantly decreases cardiovascular events and all-cause mortality in women and men. [99]Raal et al found that lipid-lowering therapy is associated with delayed cardiovascular events and prolonged survival in patients with homozygous familial hypercholesterolemia. [100]See also Cardiovascular Disease Prevention and Management Clinical Practice Guidelines (2018) by the by the Canadian Cardiovascular Harmonized National Guideline Endeavour (C-CHANGE).Diabetes managementThe goal of diabetes management is to maintain a glycosylated hemoglobin (HbA1c) concentration below 7%. Consider the following [86, 87] :Initiate lifestyle and pharmacotherapy to achieve near-normal HbA1c levels.Begin vigorous modification of other risk factors (eg, physical activity, weight management, BP control, cholesterol management) as discussed earlier.Coordinate diabetic care with the patient's primary care physician or endocrinologist.In December 2016, the US Food and Drug Administration (FDA) approved a new indication for empagliflozin (Jardiance) for reducing the risk of CV death in adults with type 2 diabetes and CVD. [101] The approval was based on findings from the EMPA-REG OUTCOME trial involving 7,020 patients in which empagliflozin produced a 38% relative risk reduction in CV mortality and a 32% risk reduction in all-cause mortality compared with placebo among the patients with type 2 diabetes, all of whom had established CVD and were already being treated with statins, ACE inhibitors, and aspirin. [102]In August 2017, the FDA has approved a new indication for liraglutide (Victoza) to reduce the risk of major adverse CV events (CV death, nonfatal MI, or nonfatal stroke) in adults with type 2 diabetes and established CVD. [103] Liraglutide is the second drug approved for glucose lowering in type 2 diabetes that has gained an additional indication for CV benefit based on results from FDA-mandated CV outcomes trials.The approval is based on the results from the LEADER trial, which demonstrated that liraglutide statistically significantly reduced the risk of cardiovascular death, non-fatal heart attack or nonfatal stroke by 13% versus placebo, when added to standard of care, with an absolute risk reduction of 1.9%.The overall risk reduction was derived from a statistically significant 22% reduction in cardiovascular death with liraglutide treatment versus placebo, with an absolute risk reduction of 1.3%, and non-significant reductions in nonfatal heart attack and nonfatal stroke. [104]See also Novel CV Risk Reduction Therapies in TD2 and CVD: Consensus Decision Pathways (ACC, 2019).Antiplatelet agents and anticoagulantsNote the following [86, 87] :As discussed earlier in the Risk Assessment and Primary Prevention section, the role of aspirin in primary prevention appears to be waning. Previously, AHA/ACCF guidelines recommended start ing aspirin 75-162 mg/day, and continuing indefinitely in all patients unless contraindicated. For patients undergoing coronary artery bypass grafting, initiating aspirin therapy (100-325 mg/day) within 6 hours after surgery to reduce saphenous vein graft closure was advised. Doses above 162 mg/day could be continued for up to 1 year.Start and continue clopidogrel 75 mg/day in combination with aspirin for up to 12 months in patients after acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) with stent placement (at least 1 month, but ideally 12 months, for bare metal stent; at least 12 months for drug-eluting stents). Patients who have undergone PCI with stent placement should initially receive higher-dose aspirin at 162-325 mg/d for 1 month for bare metal stent, 3 months after sirolimus-eluting stent, 6 months after paclitaxel-eluting stent, after which daily long-term aspirin use should be continued indefinitely at a dose of 75-162 mg. [105]Manage warfarin to an international normalized ratio (INR) of 2.0-3.0 for paroxysmal or chronic atrial fibrillation or flutter, and in post–MI patients when clinically indicated (eg, atrial fibrillation, left ventricular [LV] thrombus).Closely monitor use of warfarin in conjunction with aspirin and/or clopidogrel as this regimen is associated with an increased bleeding risk.A nationwide cohort study has suggested that treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) duration in patients with prior MI, whether short term or long term, is associated with increased risk of death and recurrent MI in patients with prior MI and is not recommended for this population. [106] NSAID use should be limited from a cardiovascular safety point of view.Renin, angiotensin, and aldosterone system blockersConsider the following regarding ACE inhibitors [86, 87] :Unless contraindicated, initiate and continue ACE inhibitor therapy indefinitely in all patients with an LV ejection fraction (LVEF) of 40% or below; in those with hypertension, diabetes, or chronic kidney disease; and consider for all other patients.ACE inhibitors may be considered optional for lower-risk patients with normal LVEF in whom cardiovascular risk factors are well controlled and revascularization has been performed.Consider the following regarding angiotensin receptor blockers (ARBs) [86, 87] :Use ARBs in patients who are intolerant of ACE inhibitors, as well as in those with heart failure or have had an MI with an LVEF of 40% or below.Consider ARBs in combination with ACE inhibitors in those with systolic dysfunction heart failure.Aldosterone blockade are used in post-MI patients without significant renal dysfunction (creatinine level should be >2.5 mg/dL in men and >2.0 mg/dL in women) or hyperkalemia (potassium level should be < 5 mEq/L), who are already receiving therapeutic doses of an ACE inhibitor and beta-blocker, have an LVEF of 40% or below, and have either diabetes or heart failure. [86, 87] One study has suggested that higher dietary potassium intake is associated with lower rates of stroke and may reduce the risk of CHD. [107]Beta-blockersStart and continue beta-blockers indefinitely in all patients who have had MI, ACS, or LV dysfunction, with or without heart failure symptoms, unless contraindicated. [86, 87]Consider chronic therapy for all other patients with coronary or other vascular disease or diabetes, unless contraindicated.Influenza vaccinationPatients with CVD should receive an influenza vaccination every year. [86, 87]Women and Coronary Artery DiseaseIn the United States, coronary heart disease (CHD) is the leading cause of death in men and women, claiming more lives than cancer, accidents, and diabetes combined. [108, 109] Although breast cancer may be more feared, age-adjusted death rates from cardiovascular disease (CVD) in women are 4 times higher in white women and 6 times higher in black women than the death rates for breast cancer.The 2010 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) report on assessment of cardiovascular risk in asymptomatic adults includes the recommendation that for all adult women and men, global risk scoring should be performed and a family history of cardiovascular disease should be obtained for cardiovascular risk assessment. [110]Compared with men, levels of low-density lipoprotein cholesterol (LDL-C) is lower and high-density lipoprotein cholesterol (HDL-C) is higher in women before menopause. Although women have lower rates of hypertension and cigarette smoking than men, rates for obesity and diabetes mellitus are higher. Diabetes mellitus is a particularly serious risk factor in women, tripling the risk of cardiovascular death and causing diabetic women to have the same frequency of CVD as diabetic men. [111, 112, 113] HDL-C and triglyceride levels are more predictive of CVD in women than in men. [114] Women have been noted to have similar or slightly higher prevalence of stable angina as compared to men. [115]It is now recognized that women tend to present more commonly with unstable angina as compared to men, the reverse of which is true for myocardial infarction (MI). However, when women do present with MI, they are more likely to have Q wave rather than non-Q wave MIs. [116, 117] Mortality rates of MI and coronary artery bypass grafting (CABG) are about 50% higher in women, mostly related to older age of onset. Lipid lowering has shown similar efficacy in women and men in the angiographic progression and event trials. Cardioprotective agents, including aspirin, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors, appear to have similar efficacy in men and women. [118, 119, 120]Hormone therapy is no longer recommended to prevent coronary events in postmenopausal women with or without established CHD. Although hormone therapy improves LDL-C and HDL-C levels, [121, 122] it also increases coagulation and inflammation (as measured by C-reactive protein [CRP]) and decreases LDL-C particle size. [5, 123] Treatment rates for risk factors in women tend to be even lower than in men, as are rates for coronary angiography and coronary artery revascularization following presentation with chest pain.Women who may have had radiotherapy through the mid-1980s to treat breast cancer are also at an increased risk of mortality from CVD. The concern is even greater if the woman was treated for a left-sided breast cancer with contemporary tangential breast or chest wall radiotherapy. [124]Finally, it must be emphasized that although the guidelines detailed above represent best practice, their formulation is often a blend of science and art. Therefore, guideline interpretation should always occur alongside good clinical judgment.

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The new guidelines departed significantly from previous iterations by abandoning the traditional LDL and non-HDL cholesterol targets.

Physicians are no longer asked to treat patients who have cardiovascular disease to an LDL of less than 100 mg/dL or the optional goal of less than 70 mg/dL.Instead, the new guidelines identify four groups of primary- and secondary-prevention patients in whom physicians should focus their efforts to reduce cardiovascular-disease events. Depending on the type of patient, physicians should choose the appropriate "intensity" of statin therapy to achieve relative reductions in LDL cholesterol.The clinical guidelines currently state that for patients with atherosclerotic cardiovascular disease, high-intensive statin therapy should be used to achieve at least a 50% reduction in LDL cholesterol unless otherwise contraindicated or when the patient experiences statin-associated adverse events. In that case, doctors should use a moderate-intensity statin.

Similarly, for those with LDL-cholesterol levels ≥190 mg/dL, a high-intensity statin should be used with the goal of achieving at least a 50% reduction in LDL cholesterol levels.

However, for patients >75 years of age and those with safety concerns and CAD, a moderate-intensity statin can be used.

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For those with diabetes aged 40 to 75 years of age, a moderate-intensity statin, defined as a drug that lowers LDL cholesterol 30-49%, should be used, whereas a high-intensity statin is a reasonable choice if the patient also has a 10-year risk of atherosclerotic cardiovascular disease exceeding 7.5%.

For the individual aged 40 to 75 years without cardiovascular disease or diabetes but who has a 10-year risk of clinical events >7.5% and an LDL cholesterol level of 70 to 189 mg/dL, the panel recommends treatment with a moderate- or high-intensity statin. Also, in a significant departure from previous guidelines, the 2013 ACC/AHA guidelines recommend measurement of LDL-C during therapy only as an assessment of adherence and response to therapy. [24]

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67. Following are known to prolong survival in acute MI

Primaty angioplasty

ACEI

Aspirin

Beta blockers

Statin

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Drugs safe to use in AF with WPW syndrome include the following

Digoxin

Verapamil

Amiodarone

Sotalol

Flecainide

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Acuired prolonged QT interval is known to be caused by

Hypercalcaemia

HypomagnesaemiaHyperkalaemiaAstemazole Erythromycin65. T/F regarding thrombolytic therapy in acute MIThrombolysis within 12 hours reduces ventricular damage and mortality rateActs in synergy with aspirin 150-300mg chewedTissue type plasminogen activator achieves higher reperfusion rates than skIV heparin therapy is mandatory after sk therapyPrimary PCI achieves higher reperfusion rates than thrombolytics66.

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WOF are beneficial in Rx in acute gout

Colchicine

Allopurinol

Corticosteroids

NSAIDs

Febuxostat

A coronary angiogram with a view to revascularization is indicated inAll post infarct ptsA positive exercise ECG at a high workload not on anti anginal medicationAll unstable angina ptsAcute anterior STEMI with CI to thrombolyticsCardiogenic shock due to post MI VSD

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Recognized causes of sinus bradycardia include

Hypoglycaemia

Cholestatic jaundice

Myocarditis

Digitalis toxicity

Raised ICP63.

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Following are red flag signs of backache in a 60 yr old female

Pain when getting up from the seated position

Presence of fever and weight lossShooting pain down the right legAssociation with bladder symptomsWorse early morning

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PathophysiologyDepending on the cause, neck or back pain may be accompanied by neurologic symptoms.If a nerve root is affected, pain may radiate distally along the distribution of that root (radicular pain). Strength, sensation, and reflexes of the area innervated by that root may be impaired. (See How to Assess Reflexes.)TABLESymptoms of Common Radiculopathies by Cord LeveliconIf the spinal cord is affected, strength, sensation, and reflexes may be impaired at the affected spinal cord level and all levels below (called segmental neurologic deficits).If the cauda equina is affected, segmental deficits develop in the lumbosacral region, typically with disruption of bowel function (constipation or fecal incontinence) and bladder function (urinary retention or urinary incontinence), loss of perianal sensation, erectile dysfunction, and loss of rectal tone and sphincter (eg, bulbocavernosus, anal wink) reflexes.Any painful disorder of the spine may also cause reflex tightening (spasm) of paraspinal muscles, which can be excruciating.

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EtiologyMost neck and back pain is caused by disorders of the spine. Muscle pain is a common symptom and is typically caused by irritation of the deeper muscles by the dorsal rami of the spinal nerve and in the more superficial muscles from a local reaction to the spine injury. Strains are very rare in the cervical and lumbar spine. Fibromyalgia can coexist with neck and back pain but is not more likely to cause pain in the neck or back. Occasionally, pain is referred from extraspinal disorders (particularly vascular, gastrointestinal, or genitourinary). Some uncommon causes—spinal and extraspinal—are serious.Vertebral Column and Spinal CordVertebral Column and Spinal Cord3D MODELMost spinal disorders are mechanical. Only a few involve infection, inflammation, cancer, or fragility fractures due to osteoporosis or cancer and are considered nonmechanical.Common causesMost pain caused by mechanical spine disorders is caused by:Disk painNerve root painArthritis of the jointsThe following are the most common causes of neck and low back pain.Disk herniationCompression fracture (usually thoracic or lumbar)Lumbar and cervical spinal stenosisOsteoarthritis throughout the spineSpondylolisthesisAll of these disorders can be present without causing pain.In the other mechanical disorders, there are no specific lesions, or the findings (eg, disk bulging or degeneration, osteophytes, spondylolysis, congenital facet abnormalities) are common among people without neck or back pain, and thus are questionable as the etiology of pain. However, the etiology of back pain, particularly if mechanical, is often multifactorial, with an underlying disorder exacerbated by fatigue, physical deconditioning, muscle pain, poor posture, weakness of stabilizing muscles, decreased flexibility, and sometimes psychosocial stress or psychiatric abnormality. Thus, identifying a single cause is often difficult or impossible.A generalized myofascial pain syndrome, such as fibromyalgia, may be a cause of neck and/or back pain.Serious uncommon causesSerious causes may require timely treatment to prevent disability or death.Serious extraspinal disorders include the following:Abdominal aortic aneurysmAortic dissectionCarotid or vertebral artery dissectionAcute meningitisAngina or MICertain GI disorders (eg, cholecystitis, diverticulitis, diverticular abscess, pancreatitis, penetrating peptic ulcer, retrocecal appendicitis)Certain pelvic disorders (eg, ectopic pregnancy, ovarian cancer, salpingitis (see Pelvic Inflammatory Disease (PID))Certain pulmonary disorders (eg, pleuritis, pneumonia)Certain urinary tract disorders (eg, prostatitis, pyelonephritis, nephrolithiasis)Extraspinal cancer metastasesSerious spinal disorders include the following:Infections (eg, diskitis, epidural abscess, osteomyelitis)Primary tumors (of spinal cord or vertebrae)Metastatic vertebral tumors (most often from breasts, lungs, or prostate)Mechanical spine disorders can be serious if they compress the spinal nerve roots or, particularly, the spinal cord. Spinal cord compression only occurs in the cervical, thoracic, and high lumbar spine and may result from disorders such as tumors and spinal epidural abscess or hematoma. Nerve compression commonly occurs at the level of a disk herniation, whether centrally with stenosis or in the foramen of an exiting nerve.Other uncommon causesNeck or back pain can result from many other disorders, such asPaget disease of boneTorticollisThoracic outlet syndromeTemporomandibular joint syndromeHerpes zoster (even before the rash)Retroperitoneal fibrosisSpondyloarthropathies (ankylosing spondylitis most often, but also enteropathic arthritis, psoriatic arthritis, reactive arthritis, and undifferentiated spondyloarthropathy)Brachial or lumbar plexus injury or inflammation (eg, Parsonage Turner syndrome)

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Testing Usually, if duration of pain is short (< 4 to 6 wk), no testing is required unless red flag findings are present, patients have had a serious injury (eg, vehicular crash, fall from a height, penetrating trauma), or evaluation suggests a specific nonmechanical cause (eg, pyelonephritis).Plain x-rays can identify most disk height loss, anterior spondylolisthesis, malalignment, osteoporotic (or fragility) fractures, osteoarthritis, and other serious bone abnormalities (eg, those due to infection or tumors), and they may be helpful in deciding whether additional imaging studies such as MRI or CT are warranted. However, they do not identify abnormalities in soft tissue (the disks) or nerve tissue (as occurs in many serious disorders).Testing is guided by findings and suspected cause. Testing is also indicated in patients who have failed initial treatment or in those whose symptoms have changed. Testing for specific suspected causes includes the following:Neurologic deficits, particularly those consistent with nerve root compression or spinal cord compression: MRI and less commonly CT myelography, done as soon as possiblePossible infection: WBC count, ESR, imaging (usually MRI or CT), and culture of infected tissuePossible cancer: CT or MRI and possibly biopsyPossible aneurysm: CT, angiography, or sometimes ultrasonographyPossible aortic dissection: Angiography, CT, or MRISymptoms that are disabling or that persist > 6 wk: Imaging (usually MRI or CT) and, if infection is suspected, WBC count and ESR; some clinicians begin with anteroposterior and lateral x-rays of the spine to help localize and sometimes diagnose abnormalitiesOther extraspinal disorders: Testing as appropriate (eg, chest x-ray for pulmonary disorders, urinalysis for urinary tract disorders or for back pain with no clear mechanical cause)

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Neck pain and back pain are among the most common reasons for physician visits. This discussion covers neck pain involving the posterior neck (not pain limited to the anterior neck) and low back pain, but it does not cover most major traumatic injuries (eg, fractures, dislocations, subluxations [see also Nontraumatic Spinal Subluxation]).GeneralBecause the cause is often multifactorial, a definitive diagnosis cannot be established in many patients. However, clinicians should determine the following if possible:Whether pain has a spinal or extraspinal causeWhether the cause is a serious disorderIf serious causes have been ruled out, back pain is sometimes classified as follows:Nonspecific neck or low back painNeck or low back pain with radicular symptomsLumbar spinal stenosis with claudication or cervical stenosis with myelopathyNeck or low back pain associated with another spinal causeHistoryHistory of present illness should include quality, onset, duration, severity, location, radiation, time course of pain, and alleviating and exacerbating factors such as rest, activity, changes in position, weight bearing, and time of day (eg, at night, when awakening). Accompanying symptoms to note include stiffness, numbness, paresthesias, weakness, urinary retention, constipation, and fecal incontinence.Review of systems should note symptoms suggesting a cause, including fever, sweats, and chills (infection); weight loss and poor appetite (infection or cancer); worsening of neck pain during swallowing (esophageal disorders); anorexia, nausea, vomiting, melena or hematochezia, and change in bowel function or stool (GI disorders); urinary symptoms and flank pain (urinary tract disorders), especially if intermittent, colicky, and recurrent (nephrolithiasis); cough, dyspnea, and worsening during inspiration (pulmonary disorders); vaginal bleeding or discharge and pain related to menstrual cycle phase (pelvic disorders); fatigue, depressive symptoms, and headaches (multifactorial mechanical neck or back pain).Past medical history includes known neck or back disorders (including osteoporosis, osteoarthritis, disk disorders, and recent or remote injury) and surgery, risk factors for back disorders (eg, cancers, including those of the breast, prostate, kidney, lung, and colon as well as leukemias; osteoporosis), risk factors for aneurysm (eg, smoking, hypertension), risk factors for infection (eg, immunosuppression; IV drug use; recent surgery, hemodialysis, penetrating trauma, or bacterial infection); and extra-articular features of an underlying systemic disorder (eg, diarrhea or abdominal pain, uveitis, psoriasis).Physical examinationTemperature and general appearance are noted. When possible, patients should be observed as they move into the examination room, undress, and climb onto the table, for an assessment of gait and balance.The examination focuses on the spine and the neurologic examination. If no mechanical spinal source of pain is obvious, patients are checked for sources of localized or referred pain.In the spinal examination, the back and neck are inspected for any visible deformity, area of erythema, or vesicular rash. The spine and paravertebral muscles are palpated for tenderness, and change in muscle tone. Gross range of motion is tested. In patients with neck pain, the shoulders are examined. In patients with low back pain, the hips are examined.How to Examine the NeckHow to Examine the NeckVIDEOThe neurologic examination should assess function of the entire spinal cord. Strength, sensation, and deep tendon reflexes are tested. Reflex tests are among the most reliable physical tests for confirming normal spinal cord function. Corticospinal tract dysfunction is indicated by upgoing great toes with the plantar response and by the Hoffman sign, most often with hyperreflexia.To test for Hoffman sign, clinicians tap the nail or flick the volar surface of the 3rd finger; if the distal phalanx of the thumb flexes, the test is positive, usually indicating corticospinal tract dysfunction caused by stenosis of the cervical cord or a brain lesion. Sensory findings are subjective and may be unreliable.The straight leg raise test helps confirm sciatica. The patient is supine with both knees extended and the ankles dorsiflexed. The clinician slowly raises the affected leg, keeping the knee extended. If sciatica is present, 10 to 60° of elevation typically causes symptoms.For the crossed straight leg raise test, the unaffected leg is raised; the test is positive if sciatica occurs in the affected leg. A positive straight leg test is sensitive but not specific for herniated disk; the crossed straight leg raise test is less sensitive but 90% specific.The seated straight leg raise test is done while patients are seated with the hip joint flexed at 90°; the lower leg is slowly raised until the knee is fully extended. If sciatica is present, the pain in the spine (and often the radicular symptoms) occurs as the leg is extended. The slump test is similar to the straight leg raise test but is done with the patient "slumping" (with the thoracic and lumbar spines flexed) and the neck flexed while the patient is seated. The slump test is more sensitive, but less specific, for disk herniation than the straight leg raise test.In the general examination, the lungs are auscultated. The abdomen is checked for tenderness, masses, and, particularly in patients > 55, a pulsatile mass (which suggests abdominal aortic aneurysm). With a fist, clinicians percuss the costovertebral angle for tenderness, suggesting pyelonephritis.Rectal examination, including stool testing for occult blood and, in men, prostate examination, is done. In women with symptoms suggesting a pelvic disorder or with unexplained fever, pelvic examination is done.Lower-extremity pulses are checked.Red flagsThe following findings are of particular concern:Abdominal aorta that is > 5 cm (particularly if tender) or lower-extremity pulse deficitsAcute, tearing upper and midback painCancer, diagnosed or suspectedNeurologic deficitFever or chillsGI findings such as localized abdominal tenderness, peritoneal signs, melena, or hematocheziaInfection risk factors (eg, immunosuppression; IV drug use; recent surgery, penetrating trauma, or bacterial infection)MeningismusSevere nocturnal or disabling painUnexplained weight lossInterpretation of findingsAlthough serious extraspinal disorders (eg, cancers, aortic aneurysms, epidural abscesses, osteomyelitis) are uncommon causes of back pain, they are not rare, particularly in high-risk groups.Red flag findings should heighten suspicion of a serious cause (see Interpretation of Red Flag Findings in Patients with Back Pain).

Other findings are also helpful. Worsening of pain with flexion is consistent with intervertebral disk disease; worsening with extension suggests spinal stenosis or arthritis affecting the facet joints. Tenderness over certain specific trigger points suggests muscle pain caused by a spinal disorder.

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TreatmentUnderlying disorders are treated.Acute musculoskeletal pain (with or without radiculopathy) is treated withAnalgesicsLumbar stabilization and exerciseHeat and coldActivity modification and rest (up to 48 hours) as neededReassuranceIn patients with acute nonspecific (nonradicular) neck or low back pain, treatment can be started without extensive evaluation to identify a specific etiology.Pearls & PitfallsTreat patients with nonspecific, nonradicular back pain who have no red flag findings symptomatically, without first requiring testing.AnalgesicsAcetaminophen or NSAIDs are the initial choice of analgesics. Rarely, opioids may be necessary, using appropriate precautions, for severe acute pain. Adequate analgesia is important immediately after acute injury to help limit the cycle of pain and spasm. Evidence of benefit for chronic use is weak or absent, so duration of opioid use should be limited.Cervical and lumbar stabilization and exerciseWhen acute pain decreases enough that motion is possible, a cervical or lumbar stabilization program is begun under the supervision of a physical therapist. This program should be started as soon as practical and includes restoration of motion, exercises that strengthen paraspinal muscles, and instruction in work posture; the aim is to strengthen the supporting structures of the back and reduce the likelihood of the condition becoming chronic or recurrent. In low back pain, "core" (abdominal and low back) muscle strengthening is important and often begins with a progression from working on a table in a supine or prone position, to quadruped (on hands and knees), and finally to standing activities.Heat and coldAcute muscle spasms may also be relieved by cold or heat. Cold is usually preferred to heat during the first 2 days after an injury. Ice and cold packs should not be applied directly to the skin. They should be enclosed (eg, in plastic) and placed over a towel or cloth. The ice is removed after 20 min, then later reapplied for 20 min over a period of 60 to 90 min. This process can be repeated several times during the first 24 h. Heat, using a heating pad, can be applied for the same periods of time. Because the skin on the back may be insensitive to heat, heating pads must be used cautiously to prevent burns. Patients are advised not to use a heating pad at bedtime to avoid prolonged exposure due to falling asleep with the pad still on their back. Diathermy may help reduce muscle spasm and pain after the acute stage.CorticosteroidsIn patients with severe radicular symptoms and lower back pain, some clinicians recommend a course of oral corticosteroids or early referral to a specialist for epidural injection therapy. However, evidence supporting the use of systemic and epidural corticosteroid use is controversial. If epidural corticosteroid injection is planned, clinicians should consider doing MRI before injection so that the pathology can be identified, localized, and optimally treated.Muscle relaxantsOral muscle relaxants (eg, cyclobenzaprine, methocarbamol, metaxalone, benzodiazepines) are controversial. Benefits of these drugs should be weighed against their CNS effects and other adverse effects, particularly in elderly patients, who may have more severe adverse effects. Muscle relaxants should be restricted to patients with visible and palpable muscle spasm and used for no more than 72 h.Rest and immobilizationAlthough a brief initial period (eg, 1 to 2 days) of decreased activity is sometimes needed for comfort, prolonged bed rest, spinal traction, and corsets are not beneficial. Patients with cervical pain may benefit from a cervical collar and contour pillow until pain is relieved and they can participate in a stabilization program.Spinal manipulationSpinal manipulation may help relieve pain caused by muscle spasm or an acute neck or back injury; however, high-velocity manipulation may have risks for patients older than 55 and those with severe disk disorders, cervical arthritis, cervical stenosis, or osteoporosis.ReassuranceClinicians should reassure patients with acute nonspecific musculoskeletal back pain that the prognosis is good and that activity and exercise are safe even when they cause some discomfort. Clinicians should be thorough, kind, firm, and nonjudgmental. If depression persists for several months or secondary gain is suspected, psy

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Geriatrics EssentialsLow back pain affects 50% of adults > 60.Abdominal aortic aneurysm (and CT or ultrasonography to detect it) should be considered in older patients with atraumatic low back pain, particularly those who smoke or have hypertension, even if no physical findings suggest this diagnosis.Imaging of the spine may be appropriate for elderly patients (eg, to rule out cancer) even when the cause appears to be uncomplicated musculoskeletal back pain.Use of oral muscle relaxants (eg, cyclobenzaprine, methocarbamol, metaxalone) and opioids is controversial; anticholinergic, CNS, and other adverse effects may outweigh potential benefits in elderly patients.

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Key PointsLow back pain affects 50% of adults > 60.Most neck and back pain is caused by mechanical spinal disorders, usually nonspecific, self-limited musculoskeletal derangements.Most mechanical disorders are treated with analgesics, early mobilization, and exercises; prolonged bed rest and immobilization are avoided.Back pain is often multifactorial, making diagnosis difficult.Serious spinal or extraspinal disorders are unusual causes.Red flag findings often indicate a serious disorder and the need for testing.Patients with segmental neurologic deficits suggesting spinal cord compression require MRI or CT myelography as soon as possible.Normal spinal cord function during physical examination is best confirmed by tests of sacral nerve function (eg, rectal tone, anal wink reflex, bulbocavernosus reflex), knee and ankle jerk reflexes, and motor strength.Abdominal aortic aneurysm should be considered in any elderly patient with low back pain that is not clearly mechanical, even if no physical findings suggest this diagnosis.In patients with acute nonradicular back pain, treatment can be started without extensive evaluation to identify a specific etiology.

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Q

recogniozed side effects of MTX include

Cirrhosis

BM suppression

Mouth ulcers

Acute interstitial pneumonitis

Maculopathy

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Adverse Effects

>10%

Arachnoiditis with intrathecal administrationSubacute toxicity with intrathecal administration (paralysis of extremities, cranial nerve palsy, seizure or coma)Demyelinating encephalopathy with cranial irradiation or other systemic chemotherapyReddening of skinHyperuricemiaUlcerative stomatitisGlossitisGingivitisNausea and vomitingDiarrheaAnorexiaIntestinal perforationMucositis (dose-dependent)LeukopeniaThrombocytopeniaRenal failureAzotemiaNephropathyPharyngitis

1-10%AlopeciaPhotosensitivityRashAbdominal distressMalaiseFatigueChills, feverDecreased resistance to infectionGastrointestinal hemorrhageMyelosuppressionDisorders of lung, interstitial pneumonia (acute, chronic)Atrophy of liver, cirrhosis, hepatic fibrosis or necrosis, elevated liver function tests, hepatic failure

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WarningsBlack Box WarningsFor use in life threatening neoplastic disease or patients with psoriasis or rheumatoid arthritis with severe recalcitrant disabling disease, not adequately responsive to other forms of therapyDeaths reported with use of methotrexate in the treatment of malignancy, psoriasis, and rheumatoid arthritisMonitor patients closely for bone marrow, liver, lung and kidney toxicitiesInform patients of risks involved; patient should be under a physician’s care throughout therapyHigh dose regimens recommended for osteosarcoma requires meticulous care; high dose regimens are investigational; therapeutic advantage not establishedNot recommended for women of childbearing potential, due to teratogenic activity, unless benefit-risk ratio is acceptableMay cause fetal death or congenital abnormalities; use is contraindicated in pregnant womenMethotrexate formulations or diluents containing preservatives should not be used for intrathecal or high-dose therapyMay cause renal damage leading to acute renal failure, especially in high dosesElimination is reduced in impaired renal function, ascites, or pleural effusions; reduce dose and monitor carefully for toxicityBone marrow suppression, aplastic anemia, and GI toxicity reported with high doses and concurrent administration of NSAIDsAny dose level or route of administration may cause severe and potentially fatal dermatologic reactionsTumor lysis syndrome may occur in patients with high tumor burdenAdminister therapy under supervision of physician experienced in use of antimetabolite therapyDiarrhea and ulcerative stomatitis may necessitate interruption of therapy; otherwise hemorrhagic enteritis and death from intestinal perforation may occurMethotrexate has been associated with acute and potentially fatal chronic hepatotoxicity; acutely, liver enzyme elevations are common but are usually transient and asymptomatic and not predictive of subsequent hepatic disease; periodic liver biopsies are recommended for psoriatic patients receiving long-term therapyLow-dose methotrexate has been associated with development of malignant lymphomasImmune suppression may lead to potentially fatal opportunistic infectionsMay cause potentially fatal pneumonitis at any time during therapy even at low doses and is not fully reversible; pulmonary symptoms (especially a dry, non-productive cough) may require interruption of therapy and careful investigationConcomitant use with radiotherapy may increase risk of soft tissue necrosis and osteonecrosisContraindicationsPregnancy: Do not use due to potential for fetal death and teratogenic effectsNursing: Do not use due to potential for serious adverse effects in infantsAlcoholism, alcoholic liver disease, or other chronic liver diseaseImmunodeficiency syndromesPreexisting blood dyscrasias such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemiaHypersensitivity: Do not use with known hypersensitivity; severe reactions have been observed with use

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CautionsOnly for use by physicians experienced in antimetabolite therapyFor intrathecal and high-dose methotrexate therapy, use preservative-free formulation; preserved formulation of methotrexate is not for intrathecal or high dose therapy; contains benzyl alcoholElderly patients: monitor closely for early signs of hepatic, bone marrow, and renal toxicityResponse in 3-6 weeks; patient may continue to improve for another 12 weeks or moreElimination reduced with renal impairment, ascites, or pleural effusions; monitor closely for renal, bone marrow, lung, or liver toxicityTaking with folic acid 1 mg/day PO may significantly reduce liver toxicityDermatologic toxicity: severe, potentially fatal skin reactions have been reported; psoriatic lesions may also be aggravated by UV radiation and sunburns may be recalled or worsenedGood oral care recommended (risk of mucositis)Use extreme caution with active infection, peptic ulceration, and ulcerative colitisImmunizations: May be ineffective during therapy and live virus vaccines are not recommended due to risk of infectionEctopic pregnancy: Ideally, human chorionic gonadotropin should be <5000 International Units/L and sonogram normalAcute and chronic hepatoxicity: Acutely, liver enzyme elevations are common but are usually transient and asymptomatic and not predictive of subsequent hepatic disease; periodic liver biopsies are recommended for psoriatic patients receiving long-term therapy; should not be used in patient with alcoholism, alcoholic liver disease, or other chronic liver diseasePulmonary toxicity: Pulmonary fibrosis, pulmonary interstitial infiltrates, and lung disease may occur acutely at any time during therapy (weekly doses >7.5 mg) but are fully reversible; symptoms (especially dry cough) may necessitate interruption of treatment and investigationMethotrexate clearance rates vary widely and are generally decreased at higher dosesGlucarpidase is indicated for treatment of toxic methotrexate concentrations in patients with delayed methotrexate clearance due to impaired renal function (refer to the glucarpidase prescribing information); if glucarpidase used, do not administer leucovorin within two hours before or after dose of glucarpidase because leucovorin is a substrate for glucarpidase; there are published case reports of intravenous and intrathecal glucarpidase treatment to hasten clearance of methotrexate in cases of overdoseGI toxicity: Diarrhea or ulcerative stomatitis warrants discontinuance of therapy (risk of hemorrhagic enteritis or intestinal perforation)Bone marrow suppression: May cause anemia, aplastic anemia, pancytopenia, leukopenia, neutropenia, and/or thrombocytopenia; use caution in patients with preexisting hematopoietic impairment and with concomitant use of NSAIDs; a significant drop in blood counts warrants discontinuation of therapyMay impair fertility, cause oligospermia, and menstrual dysfunction; exclude pregnancy before initiating treatmentNeurotoxicity: May cause neurotoxicity, including strokelike encephalopathy, seizures, leukoencephalopathy, and myelopathyNephrotoxicity: Risk of acute renal failure especially at high dosesCaution should be used while driving or operating machinery due to risk of dizziness and fatigueUse of nitrous oxide anesthesia potentiates effect on folate-dependent metabolic pathways, resulting in potential for increased toxicity such as stomatitis, myelosuppression, and neurotoxicity; avoid concomitant nitrous oxide anesthesia in patients receiving methotrexate; use caution when administering methotrexate after a recent history of nitrous oxide administration

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58. An 80 yr old male presented with painful swelling of his left knee joint of 2 weeks duration. A knee joint effusion was detected on examination.

waht is the most likely cause

Pseudogout of the knee

Trauma to the knee

Septic arthritis of the knee

Rheumatoid arthritis of the knee

Osteoarthritis of the knee

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