Department of Medicine   Department of Medicine
Readings in Internal
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Table of Contents
 
Chapter   1
CCU
Virtual CCU link
http://columbiamedicine.org/education/clinical/C_ccu.shtml
(login: residents, password: Milstein, password for the lectures: cardiology


Cardiogenic Shock
Cardiogenic shock is a common presentation in the CCU. See the review below for a good overview of the physiology and treatment.
Cardiogenic Shock: Circulation, 2008;117:686-697


PA Catheters
PA catheters are widely used in the CCU, especially for refractory heart failure patients. for an overview visit the website below and log in. Their use is controversial because the results of a randomized trial (ESCAPE: JAMA 2005; 294(13): 1625-1633) showed no benefit on a primary endpoint of number of days alive and out of the hospital at six months.
Tutorial: http://www.pacep.org/pages/start/ref.html?xin=sccm (residents, milstein)
ESCAPE Trial: JAMA 2005; 294(13): 1625-1633


Arrests
The following articles provide an overview of cardiac arrests, the benefit of early defibrillation and a clinical decision pathway for discontinuing a cardiac arrest.
Cardiac Arrests: N Engl J Med 344:1304-13 2001
Early defibrillation: N Engl J Med 348:2626-33 2003
Discontinuing Cardiac Arrests: JAMA 285:1602-6 2001

Chapter   2
Cardiology
CHF
The following article is a recent, comprehensive review of the pathophysiology, causes and treatement of acute heart failure.
Acute HF syndromes: J Am Coll Cardiol. 2009 Feb 17;53(7):557-73.


Biomarkers
Prognosis of heart failure patients is often associated with a number of different biomarkers, the following review by Brauwald highlights some of these associations.
Review: NEJM 2008 Volume 358:2148-2159

Wouldn't it be nice if we had a quick and simple blood test that would accurately tell us if a patient's acute dyspnea was caused by CHF? This prospective study examined 1586 adult patients who presented to the ED with acute dyspnea as the prominent symptom. Exclusion criteria included dyspnea clearly not secondary to CHF (i.e. trauma, cardiac tamponade, etc.), acute MI, and renal failure. BNP's were drawn on these patients on enrollment and a research assistant collected other data, including history, physical exam, blood tests and other diagnostic tests (CXR, TTE, cath, etc.), which were then reviewed by two cardiologists who were blinded to the BNP results. These cardiologists independently classified the diagnosis as 1) dyspnea due to CHF, 2) acute dyspnea due to noncardiac causes in a patient with a history of LV dysfunction, or 3) dyspnea not due to CHF. In the end, 47% were classified as group 1, 5% as group 2, and 49% as group 3. When compared to other predictor variables like age, history of CHF, history of MI, râles, cephalization of vessels, edema and JVD, a BNP level of greater than 100 was the strongest independent predictor of CHF (odds ratio 29.6). With a cut-off value of 100, BNP had a 90% sensitivity, 76% specificity and 83% accuracy for differentiating CHF from other causes of dyspnea. Additionally, there were significant increases in BNP (p < 0.001) with worsening NYHA functional class (244±286 for class I; 389±374 for class II; 640±447 for class III; 817±435 for class VI)
BNP: N Engl J Med 347:161-7 2002


B-blocker
Initial studies confirmed mortality benefit with the use of Metoprolol (Merit-HF: Lancet 1999; 353: 2001–2007) and Bisoprolol (CIBIS II: Lancet 1999; 353: 9–13). The authors of COPERNICUS chose Carvedilol for its alpha-1, beta-1, and beta-2 suppression. They showed a 35% reduction in mortality over a mean follow-up of 10.4 months in class III-IV CHF patients (EF 25%). This provided further evidence that suppressing the neurohormonal axis could delay the progression of CHF and improve survival. It is important to realize that none of these studies enrolled patients who were in the midst of decompensated heart failure or an acute exacerbation. The role of these medications in the acute setting remains controversial. However, each patient with newly diagnosed CHF who can tolerate them should be discharged on one of these three beta blockers.
Merit-HF: Lancet 1999; 353: 2001–2007
CIBIS II: Lancet 1999; 353: 9–13
COPERNICUS: N Engl J Med 2001; 344: 1651-1658


ACE-I/ARBs
This first study is a RCT evaluating the effect of Enalapril on mortality in severe CHF (class IV). It showed a 40% reduction in mortality at 6 months and 31% reduction at one year in patients treated with the ACE-I. Importantly, this decrease in mortality was from preventing the progression of CHF but had no effect on sudden cardiac death (SCD). This underscored the importance suppressing the neurohormonal axis to halt the progression of CHF. These findings have been duplicated in many different populations with multiple different ACE Inhibitors (SOLVD: N Engl J Med 1991; 325: 293–302, SAVE: N Engl J Med 1992; 327: 669–677 and ATLAS: Circulation 1999; 100: 2312–2318). Subsequent studies have shown that ARBs are acceptable options in ACE intolerant patients and may show added benefit when added to an ACE-I (VAL-HeFT: N Engl J Med 2001; 345: 1667–1675, CHARM-Alternative: Lancet 2003; 362: 772–776 and CHARM-Added: Lancet 2003; 362: 767–771).
CONSENSUS N Engl J Med 1987; 316,
SOLVD: N Engl J Med 1991; 325: 293–302,
SAVE: N Engl J Med 1992; 327: 669–677
ATLAS: Circulation 1999; 100: 2312–2318
VAL-HeFT: N Engl J Med 2001; 345: 1667–1675
CHARM-Alternative: Lancet 2003; 362: 772–776
CHARM-Added: Lancet 2003; 362: 767–771


Bi-dil
This trial was unique in that it examined a specific treatment within a specific patient population. Background data, indicated that there may be benefit of isorbide dinitrate and hydralazine amongst African Americans. This trial examined this therapy in AA patients with heart failure and found a significant reduction in mortality.
Isordil-Hyrdal: N Engl J Med 351: 2049-57


Aldo blockers
The RALES study examined spironolactone’s effect on mortality in CHF. This RCT showed that in Class III and IV CHF patients (EF35%), spironolactone reduced mortality over the average 24 month follow-up period of the study by 30%. The authors showed a reduction in deaths caused by progression of CHF as well as SCD. This study revealed that further suppression of the renin-angiotensin-aldosterone system would provide additional mortality benefit to CHF patients already on an ACE-I. These effects on mortality were replicated in post-MI patients with Epleronone (EPHESUS: N Engl J Med 2003; 348: 1309–1321). Though these results are impressive, concerns about the use of these medications outside of clinical trials and in the community have been raised. After RALES was published, there were reports of increased hospitalizations and deaths from hyperkalemia due to lack of regular follow-up and unfamiliarity with the medications. See N Engl J Med 2004; 351:. 543–551 for additional information.
RALES: N Engl J Med 1999; 341:709-717
RALES-Hyperkalemia: N Engl J Med 2004; 351:. 543–551
EPHESUS: N Engl J Med 2003; 348: 1309–1321


Digoxin
The DIG study evaluated the mortality benefit of digoxin in heart failure patients. This trial showed that digoxin did not improve mortality among patients with symptomatic heart failure.
DIG Study (N Engl J Med 336:525-33 1997)
DIG update- JAMA 2003 289:871-8


AICD
In MADIT-II (N Engl J Med 2002; 346:877-883), AICDs were shown to reduce mortality amongst patients with ischemic cardiomyopathy (EF=30%) regardless of whether they had inducible VT or not. SCD-HeFT was designed to examine whether AICD implantation was superior to anti-arrhythmic therapy amongst all comers with CHF (ischemic and non-ischemic). 2521 patients on a stable HF regimen were randomized to receive placebo, amiodarone or single lead AICD. Important inclusion criteria included stable, chronic (>3 months) class II or III HF and EF = 35%. Median follow up was 45 months with all surviving patients followed for at least 2 years. The primary outcome was mortality and showed that amiodarone and placebo had a similar risk of death (p=0.53) and that AICD implantation resulted in a decreased risk of death (p=0.007) compared to placebo. The RRR was 25% and the ARR was 7.2% resulting in a NNT of 14. The effect on mortality appears to begin 18 months after implantation. Interestingly, pre-specified subgroup analysis showed that AICD showed no benefit over placebo amongst patients with Class III HF. However, earlier trials, DEFINITE (N Engl J Med 2004; 350-2151-2158) and MADIT-II, showed a mortality benefit amongst these patients. Like MADIT-II, much of the discussion was related to the expansion of Medicare indications to include AICDs and the cost-effectiveness of implanting AICDs in a large number of patients.
MADIT-II (N Engl J Med 2002; 346:877-883)
SCD-HeFT (N Engl J Med 2005; 352: 225-237);


BiV pacing
Early studies, MIRACLE (N Engl J Med 2002;346:1845-1853), showed that patients with systolic heart failure (EF=35%) and ventricular dyssynchrony had significant improvements in quality of life, functional class and EF. The COMPANION trial (N Engl J Med 2004; 350: 2140-2150) randomized a similar set of patients to medical therapy, medical therapy + Bi-ventricular pacing, or medical therapy + BiV AICD to evaluate mortality. COMPANION was stopped early, after 12 months, due to decreased mortality in the two groups receiving cardiac resynchronization; however, the study was not powered to determine whether the mortality benefit was seen amongst patients with BiV pacing alone (p=0.06). Questions regarding long term follow up and the risks of BiV pacing were raised by meta-analyses. CARE-HF was designed to evaluate the effect of BiV resynchronization without AICD on mortality. 813 patients were randomized to standard medical therapy or medical therapy +cardiac resynchronization. Important inclusion criteria were HF for >6 weeks, Class III/IV symptoms on medical therapy, EF =35%, QRS of 120-149 msec with dyssynchrony or QRS=150 msec. Patients with an indication for PPM or AICD, any major cardiovascular event in the last 6 weeks, HF requiring IV medication or atrial arrhythmias were excluded. Mean follow up was 29 months. The primary outcome was a composite of death or unplanned hospitalization for cardiovascular event. This endpoint was significantly lower in the resynchronization group (p 0.001). Results showed a RRR of 29% for the primary outcome with an ARR of 16% giving a NNT of 7. The secondary endpoints of mortality (p0.002), quality of life (p0.001), symptoms (p0.001), EF and BNP were all improved with resynchronization. Please see J Am Coll Cardiol. 2005 Dec 20;46(12):2199-203 for an editorial on the importance of this trial.
MIRACLE (N Engl J Med 2002;346:1845-1853)
COMPANION trial (N Engl J Med 2004; 350: 2140-2150
CARE-HF (N Engl J Med 2005; 352: 1539-1549)


Normal EF
This review of the pathophysiology of HF with nl EF highlights the complexity of the field and provides the viewpoint that “diastolic dysfunction” may not be the only explanation.
Normal EF Heart Failure: Current Heart Failure Reports 2009, 6:57–64)
ACS
Heparin
The initial studies on heparin for anticoagulation were done in patients undergoing thrombolysis for STEMI. Studies showed that improved vessel patency with heparin and use of a fibrinolytic. As PCI was shown to result in more favorable outcomes, heparinization was found to be essential during PCI in order to prevent acute vessel closure. In UA/NSTEMI patients, heparin and ASA have been shown to further reduce death and MI. Lovenox has been compared to UFH for UA/NSTEMI and appears to show improved outcomes; however, UFH is often used as it proves easier to control if a patient is undergoing PCI.
Heparin and thrombolysis-Am J Cardiol 1996;77:551-6
Heparin with PCI-Circulation 1996;93:667-71.
Heparin and ASA: JAMA 1996;276:811-15
Lovenox vs. UFH- N Engl J Med 1997;337:447-452


ASA
Statin
Studies like the Heart Prevention Study, showed that statins reduced the rate of death or CV events and MIRACL showed high dose therapy used early in ACS decreased adverse events. PROVE-IT takes it a step further by showing that this intensive therapy provided a greater protection, hypothesizing that decreasing LDL to even lower levels is more beneficial. Patients got 80mg of atorvastatin or 40mg pravastatin plus ASA with or without plavix. Patients had ACS with or without EKG changes, or unstable angina in the last 10 days (1/3 were unstable angina, 1/3 NSTEMI and 1/3 STEMIs). Important exclusion criteria included serious hepatic disease and creatinine greater than 2. Primary end point was a composite including: 1) Death from any cause 2) MI 3) Unstable angina requiring re-hospitalization 4) PCI or CABG within a month 5) CVA. There was a 22% reduction in LDL in standard therapy vs. 51% reduction in high dose group. At two years, PROVE-IT showed a 16 percent reduction in the HR of the composite favoring high dose treatment. Furthermore, this benefit was seen as early as 30 days and was consistent over time, across all subgroups and individual components of composite, except for rate of CVA which was similar between both groups. However, one thing to keep in mind is that the study does not allow us to say definitively if it is the degree of decrease in LDL or other pleiotropic effects of atorvastatin that account for its superiority over low dose pravastatin. For an editorial on this article see N Engl J Med 2004;350:1562-1564.
Coronary Prevention Study (N Engl J Med 1995; 333:1301-1308)
MIRACL (J Am Med Assoc. 2001;285:1711–1718)
PROVE-IT (N Engl J Med 2004; 350: 1495-1504)


Plavix
The benefit of plavix in conjunction with ASA and unfractionated heparin was shown to substantially reduce rate of MI in patients undergoing PCI. PCI-CURE was designed to see if this would hold true in pts with ACS and NSTEMIs as well, within an accepted margin of safety. Patients were those hospitalized within 24 hours of onset of symptoms and had EKG changes or elevation in cardiac enzymes. Important exclusion criteria were high risk for bleeding, current anticoagulation, or severe heart failure. Pts were randomized to placebo and ASA or plavix and ASA. There was a reduced risk of a composite including death from CV events, nonfatal MI, or CVA in the plavix group (9.3% vs. 11.4%, RR 0.8, CI 0.72-0.9, P0.001) which was seen within the first 30 days and extended to 1 year. Of note, when looking at the individual components there was no real difference in death from CV causes (5.1% vs. 5.5%, RR 0.93, CI 0.79-1.08)), but a reduction in MI (5.2% vs. 6.7%, RR 0.77, CI .67-.89) and refractory ischemia during the initial hospitalization (1.4% vs. 2%, RR 0.68, CI 0.52-0.9). Safety was also examined and major bleeding was significantly more common in the plavix group (3.7% vs. 2.7%, RR 1.38, CI 1.13-1.67), both before and after the first 30 days. Thus, CURE shows us why plavix has earned its place on our ACS blue cards, though we must remember to take the increased risk of bleeding seriously when giving it to our more high risk patients. NEJM subsequently published a cost-effectiveness study to highlight the great expense associated with clopidogrel therapy.
Dual antiplatelet Tx: JAMA 288:2411-20 2002
PCI-CURE study: Lancet 358:527-33 2001
Cost Effectiveness: N Engl J Med 346:1800-6 2002


B-blockers
Trials with IV and oral beta blockers have been done in patients presenting with STEMI with a number of conflicting results. The ACC/AHA guidelines do favor the use of beta blockers in patients presenting with MI. Oral beta blockers should be started in all patients without contraindications (heart failure, bradycardia, active bronchospasm, low output state). IV beta blockers can be used in hypertensive patients who are not at risk of cardiogenic shock. These guidelines have also been adopted for UA/NSTEMI though trials are lacking in this patient population.
Beta blocker with Thrombolysis. Circulation 1991;83: 422-37
Beta Blocker with MI Lancet 2005;366:1622-1632
Beta Blocker with PCI J Interv Cardiol 2003;16:299-305


Bivalirudin
Guidelines recommend the use of ASA, plavix, GIIb/IIIa inhibitor and unfractionated or low-molecular weight heparin for UA/NSTEMI patients who are to undergo PCI. REPLACE-2 showed that replacing heparin and GIIB/IIIA with Angiomax, or bilvalirudin, monotherapy in low risk patients for elective PCI could provide similar benefit as above therapy, but with reduced bleeding. ACUITY shows this to be true when also used in ACS patients with high risk unstable angina or NSTEMIs. Patients included had unstable angina within 24 hours of admission with NSTEMIs or increase in cardiac enzymes. Important exclusion criteria were STEMIs, recent anti-coagulation therapy, or Cr clearance30. Patients were randomized to heparin or enoxaparin plus GPIIb/IIIa inhibitor, bivalirudin plus GPIIb/IIIa inhibitor, or bivalirudin monotherapy. All patients had angiography within 72 hours and were then triaged to PCI (56%), CABG (11%) or medical management (33%). Patients had an average age of 63, 59% were classified as having NSTEMIs and 41% unstable angina, and while almost all received ASA prior to catheterization, only a little over of 60% got plavix. Angiomax with GPIIb/IIIa vs. heparin with GPIIb/IIIa resulted in similar rates of primary endpoints (death from any cause, MI, unplanned revascularization or major bleeding). However, Angiomax monotherapy when compared to the latter showed non-inferior rates of ischemia, but significant reduced rates of bleeding (3% vs. 5.7%, RR 0.53, CI 0.43-0.65). Thus, ACUITY suggests that replacing heparin and GPIIb/IIIa with bivalirudin monotherapy provides the same benefit in reducing ischemia events with a reduction in the important risk of bleeding. For a very good critique of the study,: N Engl J Med. 2006;355:2249-50.
ACUITY- N Engl J Med 2006;355:2203-2216
ACUITY Editorial- N Engl J Med. 2006;355:2249-50


IIB/IIIA inhibitors: for STEMI/PCI
The CADILLAC trial evaluated glycoprotein IIB/IIIA inhibitors in patients undergoing PCI. The trial showed that a composite endpoint of death, MI, stroke and revascularization was lower in patients who received stents as opposed to PTCA alone regardless of the use of IIB/IIIA inhibitor. This was in contrast to many other prior trials. Subsequent meta- analyses have shown morbidity and mortality benefit amongst patients undergoing PCI; therefore the guidelines have stated that these medications should be started in patients undergoing PCI.
CADILLAC: N Engl J Med 2002;346:957-66
JAMA Meta-analysis: JAMA 2005 Apr 13;293(14):1759-65
Meta-analysis: Lancet 2002;359:189-198.


Thrombolysis/PCI:
These articles evaluate the mortality benefit from thrombolysis and PCI for MI. The FTT group reviews the indications for thrombolysis amongst patients with PCI. Meta analyses have shown that PCI is superior to Thrombolysis alone.
Thrombolysis Lancet 1994;343:311-22
PCI vs. Thrombolysis: Lancet 2003; 361: 13–20

TACTICS evaluated the use of PCI amongst patients with UA/NSTEMI versus a conservative medical management. A composite endpoint of death, MI, or hospitalization was less in the PCI group; however, there was no mortality benefit. The reduction in composite endpoint was seen exclusively in patients with troponin elevations.
TACTICS N Engl J Med 2001;344:1879-1887


Other Causes of ST Elevations
Not all ST elevations are caused by MIs. This article reviews the other causes of ST elevations.
Non ACS ST Elevations: NEJM 2003 349:2128-2135


Clinical Decision-Risk Assesment
For patients with acute myocardial infarction, the beneficial effects of reperfusion therapy are greatest when performed soon after the onset of symptoms. In other words, “time is myocardium.” With the EKG being the primary tool to select for patients that would best benefit from immediate reperfusion therapy, what does one do when a patient presents with symptoms of an acute myocardial infarction and an EKG revealing a left bundle-branch block with no previous EKG's available for comparison? It was widely believed that acute myocardial injury could not be detected via EKG in patients with left bundle-branch block. The GUSTO-1 trial tried to help manage this dilemma by comparing the EKG's of patients who had an acute myocardial infarction by enzymes and a baseline LBBB with the EKG's of an equal number of patients with stable angiographically documented CAD and complete LBBB but no chest pain at the time of EKG. The trial concluded that the three electrocardiographic criteria with independent value in the diagnosis of acute infarction were ST-segment elevation of at least 1mm that was concordant with the QRS (odds ratio 25.2!!), ST-segment depression of at least 1mm in V1, V2 or V3 (odds ratio 6), and an ST-segment elevation of at least 5mm that was discordant with the QRS (odds ratio 4.3). For a great review article of EKGs in acute MIs, check out: Zimetbaum P, Josephson M. Use of Electrocardiogram in Acute Myocardial Infarction. N Engl J Med 2003;348:933-940.
Sgarbossa: N Engl J Med 334:481-7 1996

Using the database of the TIMI 11B and ESSENCE trials (both phase III, international, randomized, double-blind trials which compared treatment with unfractionated heparin vs. enoxaparin in patients with UA/NSTEMI), twelve variables at presentation were examined with respect to a composite end-point of all-cause mortality, new or recurrent MI, or severe recurrent ischemia prompting urgent revascularization through 14 days. Seven of the 12 variables were statistically significant and formed the final set of predictor variables: 1) age greater than 65; 2) greater than 3 risk factors for CAD (family history, HTN, hyperlipidemia, DM, current smoker); 3) prior coronary stenosis of greater than 50%; 4) ST-segment deviation on EKG at presentation; 5) at least 2 anginal events in the prior 24 hours; 6) use of aspirin in the prior 7 days; 7) elevated serum cardiac markers. Event rates increased significantly as the TIMI risk score increased (0/1: 4.7%, 2: 8.3%, 3: 13.2%, 4: 19.9%, 5: 26.2%, 6/7: 40.9%). Three validation cohorts were used to validate these findings.
TIMI risk score: Antman EM, Cohen M, et al. JAMA 2000; 284: 835-842


Arrhythmia
A-fib
In this landmark study comparing rhythm vs. rate control for control of complications related to atrial fibrillation, 4060 patients with average age 69.7 +/- 9.0 years were randomized to either rhythm control (with any of multiple agents, although 2/3 were on amiodarone and the majority of patients started with amiodarone or sotalol) or rate control (with beta blockers, calcium channel blockers or digoxin). Patients were followed for a mean of 3.5 years. Primary analysis demonstrated a trend toward mortality benefit in the rate control group (hazard ratio 1.15 with 95% confidence interval 0.99 to 1.34). Secondary analysis did demonstrate significantly lower rates of hospitalization (1220 vs. 1374), significantly lower torsades de pointes (2 vs. 12) and PEA/bradycardic arrests (1 vs. 9) in the rate control group. Rates of stroke were similar in the two groups, and stroke (77 vs. 80) appeared to be related to discontinuation of anticoagulation. An editorial in the same issue of NEJM by Dr. Falk suggested that although this study represented a landmark in the treatment of atrial fibrillation, inclusion criteria for this study included age >65, so caution should be used when applying this study to the management of Afib in younger patients and patients with no structural heart disease. And most importantly, appropriate anticoagulation, even in the setting of rhythm control, is the most important factor in reducing stroke risk in this population.
Affirm (N Engl J Med 347:1825-33 2002)

CHADS2, among other risk stratification schemes, was validated prospectively for patients' stroke risk based on clinical factors (CHADS2 = 1 point for each of the following: CHF, HTN, Age >75, Diabetes, and prior stroke/TIA (2 points)). CHADS2 was particularly effective at stratifying people at high risk for stroke, while still being as effective as other schemes in classifying patients as low-risk, in whom the risks of anticoagulation outweigh the potential benefits. Regarding the clinical scenario, this patient has 4 points by CHADS2 and would be classified as high-risk, with a risk of 5.3 strokes per 100 patient-years in those without a prior history of stroke (primary prevention). The benefits of anticoagulation outweigh the risks and this patient should be started on coumadin. Of note, this validation study only included clinical factors. TTE results were not available, which may have helped to improve the predictive accuracy of those schemes that use LV systolic dysfunction as a predictor of stroke risk.
CHADS 2: Circulation 2004;110:2287-2292

Active-A was designed to evaluate the use of plavix and ASA vs. ASA alone for patients with a-fib in patients who were intolerant to Coumadin. While this study did show a decrease in major vascular events, it came at the expense of increased bleeding.
Active-A: N Engl J Med 2009;360:2066-78

Protect –AF was recently presented and evaluated the use of the Watchman device to close the left atrial appendage. The article has not been published yet.
Protect-AF: Not Yet Published


Brugada
This is an update on Brugada Syndrome from one of the original authors.
Brugada Syndrome: Prog Cardiovasc Dis. 2008 Jul-Aug;51(1):1-22.


BMJ EKG articles
Review articles on atrial, junctional and wide complex arrhythmias from the British Medical Journal.
Atrial arrhythmias: BMJ 2002;324:594-597 ( 9 March )
Junctional Arrhythmias: BMJ. 2002 Mar 16;324(7338):662-5
WCT I: BMJ  2002;324:719-722
WCT II: BMJ 2002 Mar 30;324(7340):776-9.
O/P + Prevention
ASA for primary prevention
The issue of ASA for primary prevention is unclear especially amongst certain populations (women). These articles review the evidence and present the current recommendations.
Meta Analysis: Lancet 2009; 373: 1849–60,
USPSTF for ASA prevention: Ann Intern Med 2009 Mar 17;150(6):396-404


AAA screening
HTN-Hyperlipidemia
These articles contain the current recommendations for blood pressure and cholesterol levels. Also included are the DASH and Premier studies which showed how effective lifestyle modification could be to reduce risk. The ACCOMPLISH trial was recently published and showed that and ACE plus Calcium channel blocker may be a more effective BP regimen than an ACE plus diuretic.
DASH: N Engl J Med 344:3-10 2000
Premier: JAMA 289:2083-93 2003
JNC-7: JAMA 289:2560-72 2003,
ATP III: Circulation. 2004;110:227-39

Why do we always use HCTZ as our first line of defense in patients with hypertension? In the landmark ALLHAT trial, a randomized, double-blind, active-controlled clinical trial conducted from February 1994 through March 2002, the authors set out to determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowered the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs. treatment with a diuretic. A total of 33, 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15 255), amlodipine, 2.5 to 10 mg/d (n = 9048), or lisinopril, 10 to 40 mg/d (n = 9054) for planned follow-up of approximately 4 to 8 years. The primary outcome was combined fatal CHD or nonfatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-cause mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure, and peripheral arterial disease). The primary outcome occurred in 2956 participants, with no difference between treatments. All-cause mortality also did not differ between groups. Five-year systolic blood pressures were significantly higher in the amlodipine (0.8 mm Hg, P03) and lisinopril (2 mm Hg, P001) groups compared with chlorthalidone. For amlodipine vs. chlorthalidone, secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine (10.2% vs. 7.7%; RR, 1.38; 95% CI, 1.25-1.52). For lisinopril vs. chlorthalidone, lisinopril had higher 6-year rates of combined CVD (33.3% vs. 30.9%; RR, 1.10; 95% CI, 1.05-1.16); stroke (6.3% vs. 5.6%; RR, 1.15; 95% CI, 1.02-1.30); and HF (8.7% vs. 7.7%; RR, 1.19; 95% CI, 1.07-1.31). This study therefore provides strong evidence that thiazide-type diuretics are superior in preventing one or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy
ALLHAT: JAMA 288:2981-97 2002

The ACCOMPLISH trial was recently published and showed that and ACE plus Calcium channel blocker may be a more effective BP regimen than an ACE plus diuretic (HCTZ). This indicates that our routine practice of starting with a diuretic may not actually be the best choice.
ACCOMPLSH: N Engl J Med 359:2417, December 4, 2008

The HOPE trial assessed the use of ACE-I in high risk patients without known LV dysfunction. Initially the study was hailed for the finding that ACE-I use was more protective even if BP lowering was accounted for. However, some controversy has arisen regarding the magnitude of the BP lowering effects.
HOPE: JAMA 2001 Jul 25;286(4):421-6

This landmark study evaluated the use of statin to lower cholesterol in patients with hypercholesterolemia but no known cardiovascular disease. The use of pravastatin was associated with a 22 percent reduction in mortality and a reduction in all major cardiovascular events.
Coronary prevention study:  N Engl J Med 1995; 333:1301-1308


PAD: Review
These articles review the symptoms, diagnosis and treatment of PAD. Also included is the largest randomized trial for PAD evaluating the treatment of intermittent claudication with cilostazol.
Lancet Review: Lancet 2001; 358: 1257–64
NEJM review: NEJM 2001; 344;1608-1621
Cilostazol: Arch Intern Med. 1999;159:2041–50

Chapter   3
GI
GI bleed
UGI bleeds
A prior study by the same group (N Engl J Med 2000;343:310-316) evaluated the use of IV omeprazole after hemostasis with endoscopy in order to prevent recurrent bleeding. That study showed that IV PPI infusion for 72 hours post-endoscopy followed by 20 mg PO for 8 weeks reduced recurrent bleeding at 3 months. This forms the basis for our post endoscopy management of UGI bleeds. This study was aimed at evaluating PPI infusion prior to endoscopy to evaluate active bleeding and length of stay. Important inclusion criteria included UGI bleed with melena or hematozchezia and volume responsive shock. Importantly, long term ASA users were excluded from the study. 638 patients were randomized to receive omeprazole or placebio prior to endoscopy. The authors found fewer actively bleeding ulcers in the omeprazole group vs. the placebo group (6.4% vs. 14.7%, p = 0.01). There was also a reduction in hospital stay in the omeprazole group (p = 0.005). However, there were no differences in the amount of blood transfused, emergent surgeries performed, and 30-day mortality. With this information, we routinely place patients on a PPI pre- and post-endoscopy, although the optimal duration, dosage, and formulation (oral vs. IV) remain controversial.
PPI post endoscopy: N Engl J Med 2000;343:310-316
PPI pre endoscopy: N Engl J Med 2007;356:1631-1640
Variceal bleeds
This double-blind, randomized trial compared the use of propranolol vs. placebo in the prevention of the first episode of variceal bleed in patients with documented portal hypertension and documented esophageal varices. Patients randomized to propranolol had a reduction in first variceal bleed compared to patients randomized to placebo (4% vs. 22%) after a mean follow-up of 16.3 months, but there was no significant decrease in mortality. The study used the hepatic vein pressure gradient (HVPG < 12 mm Hg) as a guide to dosing propranolol in the study. Since an HVPG < 12 mm Hg has been shown to virtually eliminate the risk of variceal bleeding, it is an ideal guide for beta-blocker dosing. However, HVPG measurement is both an invasive and expensive means to titrate beta-blocker dosing and is impractical in the clinical setting. Thus, titration of doses to HR 50-60 is generally used. This may, however, blunt the benefit that was seen in the study.
Beta blockers
This double-blind, randomized trial compared the use of propranolol vs. placebo in the prevention of the first episode of variceal bleed in patients with documented portal hypertension and documented esophageal varices. Patients randomized to propranolol had a reduction in first variceal bleed compared to patients randomized to placebo (4% vs. 22%) after a mean follow-up of 16.3 months, but there was no significant decrease in mortality. The study used the hepatic vein pressure gradient (HVPG < 12 mm Hg) as a guide to dosing propranolol in the study. Since an HVPG < 12 mm Hg has been shown to virtually eliminate the risk of variceal bleeding, it is an ideal guide for beta-blocker dosing. However, HVPG measurement is both an invasive and expensive means to titrate beta-blocker dosing and is impractical in the clinical setting. Thus, titration of doses to HR 50-60 is generally used. This may, however, blunt the benefit that was seen in the study..
Propranalol for Varices Hepatology 1991;13:902-912


Somatostatin analogs/Terlipressin
These studies evaluate the use of octreotide (a somatostatin analog) and Terlipressin. While some studies indicate that Terlipressin may, in fact, have more beneficial hemodynamic effects compared to octreotide, the easy availability in the US makes octreotide the choice for active variceal bleed.
Terlipressin: Cochrane Database Syst Rev 2003;(1):CD002147 
Octreotide and Scleropathy: N Engl J Med 1995 Aug 31;333(9):555-60
Early administration of Somatostatin analog-N Engl J Med 2001 Jan 4;344(1):23-8
Oct vs. Terlipressin Am J Gastroenterol. 2005 Mar;100(3):631-5. 
LGI-c-scope
While emergent endoscopy is often a first line treatment for UGI bleed, the utility of colonoscopy to emergently or urgently treat lower GI bleed is less clear. This is a comparison of two non-randomized, prospective trials done by the same authors looking at the utility of urgent (6-12 hours after admission) colonoscopy, after bowel prep, in the management of diverticular hemorrhage. The initial, early prospective study involved 73 patients. Colonoscopy was used to diagnose diverticular hemorrhage in 17patients (23%) that were treated with standard medical therapy. If these patients had continued bleeding, they received transfusions and, if necessary, underwent emergency hemicolectomy. The second trial used urgent colonoscopy on the subsequent 48 patients to diagnose and endoscopically treat diverticular hemorrhage in 10 patients (21%). The authors compared the outcomes in the two patient populations. Of the 17 patients treated medically, 9 patients required additional transfusions and 6 underwent emergency hemicolectomy. Of the 10 patients treated endoscopically, no patient required additional transfusions or surgery. None of the patients in either group had recurrent bleeding at 30 days. While this paper has several limitations in terms of its’ design and endpoints, it did show that diverticular hemorrhage may be amenable to endoscopic therapy in a similar fashion to UGI bleeds. Despite this potential, lower GI bleeds only make up 20% of all GI bleeds and diverticular bleeds amenable to endoscopic therapy are an even smaller proportion. The optimal timing of intervention is also unclear, mostly due to the study design. For these reasons, patients with lower GI bleed are not rushed to the endoscopy suite for emergency colonoscopy. Please see the editorial (N Engl J Med 2000; 342:125-127) for further information.
Colonoscopy for LGI bleed: N Engl J Med, 2000; 342: 78-82
Pancreatitis
Antibiotics
Initial studies on the use of prophylactic antibiotics during the 1970s showed no benefit. Subseqeuntly, a few studies have shown that patients with severe acute pancreatitis appeared to benefit from antibiotic prophylaxis. Despite this, later larger, randomized trials again failed to show a benefit. The collection of articles below highlight the ambiguity in this subject.
Prophylactic abx for pancreatitis: Gastroenterology 2004 Apr;126(4):997-1004
Early abx treatment for pancreatitis: Lancet 1995 Sep 9;346(8976):663-7
Evidence based Treatment for acute pancreatitis: Ann Surg. 2006 Feb;243(2):154-68


Feeds
Early feeding has been a recent trend in pancreatitis largely due to trials showing a benefit from enteral feeding compared to parenteral feeds as well as a lack of benefit from post pyloric feeds compared to NG tube feeds.
Enteral vs. Parenteral Feeds: BMJ 2004 Jun 12;328(7453):1407. Epub 2004 Jun 2
Early Feeding: Am J Gastroenterol 2005 Feb;100(2):432-9


BISAP
Clinical prediction rules for acute pancreatis have been limited to Ranson’s criteria as well as the APACHE-II score. This article describes a simple bedside algorithm for assessing risk amongst patients presenting with pancreatitis.
Am J Gastroenterol 2009; 104:966–971;


Early ERCP
RCTs suggested strong evidence that early ERCP reduces the complication rate in patients with severe biliary pancreatitis as well as the incidence of biliary sepsis (Fan et al. NEJM 1993;328:228-232) despite having no effect on mortality outcome. These studies, however, focused on patients with obstructive jaundice and bilirubin up to 37; do the benefits of early ERCP extend to patients with non-obstructive biliary pancreatitis? In order to address this question, the investigators randomized 238 patients with evidence of biliary pancreatitis (by US or CT or 2/3 of alk phos>125, ALT>75, and bili >2.3) to receive early ERCP (within 72 hours) vs. conservative management. Of note, 101 were excluded for exclusion criteria including temperature >39C, bilirubin >5, and onset of symptoms >72 hours. In the conservative management, 20% required ERCP within 3 weeks of randomization. The overall mortality and mortality due to pancreatitis at 3 months showed no statistically significant difference between the two groups. Respiratory complications were more significant in the treatment group whereas jaundice and cholecystitis were more prevalent in the conservative management group. These data suggest that early ERCP in patient without obstructive jaundice is not beneficial.
with jaundice N Engl J Med 1993 Jan 28;328(4):228-32
without jaundice N Engl J Med 1997; 336:237-242
Liver
LFT abnormalities
Assessing LFT abnormalities is a daily event on the wards. These articles review LFTs and what their abnormalities indicate.
LFT review: Gastroenterology. 2002 Oct;123(4):1367-84
LFT abnormalities: N Engl J Med. 2000 Apr 27;342(17):1266-71


Acute Liver Failure
This review explains the diagnosis, consequences and therapeutic options for patients with acute liver failure.
Journal of clinical gastroenterology 2001:33(3):191-198


Cirrhosis
The benefit of diruetics for patients with cirrhosis and ascites was demonstrated long ago. This paper established the intial dosage of furosemide and spironolactone in treating patients with ascites from cirrhosis.
Diuretics in Cirrhosis: J Clin Gastroenterol 1981;3 Suppl 1:73-80

    In patients presenting with cirrhosis and SBP, renal impairment is a frequent complication, and Navasa M et al. previously described an association between SBP and an increase in the renin-angiotensin system. (Navasa M, et al. Hepatology 1998;27:1227-1232). Therefore, in this study, the authors hypothesized that volume expansion with albumin would benefit renal function in patients with SBP. Patients receiving cefotaxime and albumin, compared to those receiving cefotaxime alone, had decreased renal impairment (10% vs. 33%), in-house death (10% vs. 29%), and 3-month mortality (22% vs. 41%). However, the study used a substantial amount of albumin, costing $875 to $4375 for a 70kg patient, and the study does not detail fluid management in the group receiving cefotaxime alone, so it’s unclear if the patients would have benefited from crystalloid replacement alone
    Albumin for LVP: Gastroenterology 1988;94:1493-1502

    These articles review the pathogensis and complications of cirrhosis and liver failure.
Alcoholic Hepatitis
The use of steroids in alcoholic hepatitis remains controversial. In this randomized, double-blinded study, 28-day treatment with prednisolone vs. placebo was compared in patients with severe biopsy-proven alcoholic hepatitis (Discriminant Function >32). Prednisolone is favored over prednisone because prednisone is converted to its active form, prednisolone, in the liver. This study showed a decrease in 66-day mortality with use of prednisolone (45% vs. 88%). Primarily based on this study as well as two other RCTs (Mendenhall et al NEJM 1984;311:1464 and Carithers et al Ann Intern Med 1989;110: 685), the American College of Gastroenterology has proposed guidelines for treating patients with prednisolone in the setting of severe alcoholic hepatitis with discriminant function >32 and/or hepatic encephalopathy (McCullogh AJ, et al. American Journal of Gastroenterology 1998;93:2022-2036). These guidelines, however, have remained controversial given that other studies have not shown a benefit from steroids (Depew W et al Gastro 1980;78:524 and Blitzer et al. Am J of Diges Dis 1977;22:477) and the largest RCT (Mendenhall et al.) was not stratified by discriminant function data. Although meta-analyses still disagree, a recent analysis of the individual data (Mathurin et al. J Hepatol 2002;36:480) supports the short term benefit of corticosteroids.
Steroids: N Engl J Med 1992;326(8):507-512


SBP
This study showed the role of albumin in patients undergoing repeated large-volume paracentesis (4-6L per day until the disappearance of ascites). Infusion of albumin was not associated with significant changes in renal function, plasma renin activity, and plasma aldosterone whereas patients without albumin showed significant increase in BUN, plasma renin activity and plasma aldosterone. The albumin group had fewer patients who developed renal impairment (defined as >50% increase in Cr or BUN) and/or hyponatremia as compared to the control group (1.7% vs. 20.8% P=0.01). This study showed no direct mortality benefit with albumin, and the use of albumin with its inherent cost remains controversial. Additional studies have shown that albumin may have little benefit in paracenteses less than 5L.
Albumin and SBP: N Engl J Med 1999;341:403-409
Norfloxacin
Trials in patients with high risk features for SBP have evaluated the use of prophylaxis to prevent SBP (both intermittent and continuous). Meta-analyses have shown some mortality benefit in selected patient populations. However, the is0.sue remains unsettled as a cost analysis revealed a benefit only in patients who have a history of SBP.
SBP PPx intermittent vs. continuous: Hepatology 1997 Mar;25(3):532-6.
Primary SBP PPx: Gastroenterology. 2007 Sep;133(3):818-24. Epub 2007 Jul 3,
cost of SBP PPx: Gastroenterology 1997 Oct;113(4):1289-94
O/P + Prevention
HBV/HCV
These are the clinical practice guidelines for patients with HCV and HBV in the outpatient setting.
HBV guidelines: HEPATOLOGY, Vol. 45, No. 2, 2007
HCV guidelines: HEPATOLOGY, Vol. 49, No. 4, 2009


Diarrhea
These articles review the evaluation of both acute and chronic diarrhea.
Acute Infectious Diarrhea: N Engl J Med 350:38, January 1, 2004
Chronic diarrhea: N Engl J Med 355:236, July 20, 2006 Perspective


Colon CA screening
Colon CA screening is often done with colonscopy; however, FOB has been shown to have an impressive reduction in mortality in repeated studies. Sigmoidoscopy and Colonoscopy are thought to have similar benefit as they are considered more sensitive and specific tests; however, the evidence is not necessarily as strong.
FOB screening-Gut 2002 Jan;50(1):29-32
Sigmoidoscopy-Selby, JV; Friedman GD; Quesenberry CP Jr; Weiss NS, NEJM 1992. Mar 5; 326 (10): 653-657
   
Chapter   4
Pulmonary
The American thoracic society has a reading list with many of the important pulmonary and critical care articles.
ATS website
MICU
MICU curriculum
MICU curriculum (residents, milstein)

CVP Monitoring
This article is an update from Rivers regarding the use of CVP monitoring within the Medical ICU.
Central Venous Monitoring -Current opinion in critical care 2001, 7:204-211


Surviving Sepsis Campaign
This is the recently published surviving sepsis guidelines which highlights the management of sepsis within the ICU setting.
Surviving Sepsis Campaign crit care med 2008 vol 36, no 1
PE
Clinical Decision making
This study evaluated 946 patients, and based on the criteria, divided them into low, moderate and high probability of having a PE. These criteria included: clinical signs and symptoms of DVT (3 points), PE as the most likely diagnosis (3 points), tachycardia (1.5 points), immobilization for at least 3 days or surgery within the previous 4 weeks (1.5 points), previous objectively diagnosed PE or DVT (1.5 points), hemoptysis (1 point), and malignancy (1 point). Risk score interpretation (probability of PE) was the following: >6 points: high risk (78.4%); 2 to 6 points: moderate risk (27.8%);2 points: low risk (3.4%) Based on their pre-test probability, further tests to risk stratify these patients included D-dimer, V/Q scan, and LE ultrasound. They treated patients found to have PE or DVT by V/Q and LE ultrasound and followed all patients for 3 months. The proportion of patients found to have PE was 1.3% of the low probability group, 16.2% of the moderate probability group, and 37.5% of the high probability group. Of the 849 patients not treated for PE, 5 (0.6%) developed PE or DVT in follow-up. In low suspicion of PE, a normal D-dimer level was shown to be enough to exclude the possibility of thrombotic PE without ordering other excessive diagnostic modalities.
D dimer: Annals Intern Med 2001;135:98-107

The Christopher Study prospectively followed a large cohort of patients with suspected PE and implemented a diagnostic algorithm that used a previously validated clinical decision rule (Table 1) to divide the pts into PE “likely” (>4 points) or “unlikely” (=4 points). Those categorized as “unlikely” received D-Dimer testing, and normal D-Dimer (= 0.5 ug/ml) excluded the diagnosis of PE with follow-up showing 1% incidence of venous thromboembolism at 3 months. Pt with “likely” PE and/or those with abnormal D-Dimer (>0.5 ug/ml) went on to CT, and most of those with negative CT scan did not receive anticoagulation with incidence of VTE on 3 months follow-up at 1.3%. By following the diagnostic algorithm outlined in the Christopher Study, one could begin to approach PE with more certainty and appropriately triage diagnostic studies and treatment.
Christopher Study: JAMA. 2006 Jan 11;295(2):172-9

This is the most extensive study evaluating the use of V/Q scan in the diagnosis of PE. Compared to a reference standard of pulmonary angiography, the V/Q scan had the greatest diagnostic accuracy when combined with clinical judgement. A normal V/Q scan virtually eliminated PE and a high prob scan in a high likelihood patient had a 95% likelihood of having PE.
PIOPED: JAMA 263:2753-9 1990


COPD-inpatient
ATS clinical guidelines
These are the current American Thoracic Society guidelines for the diagnosis and treatment of COPD.
Eur Respir J 2004 Jun;23(6):932-46


Antibiotics
The rationale for the role of antibiotics in COPD exacerbations is as a result of multiple placebo-controlled trials and retrospective population analyses. One of the largest (Ann Intern Med 1987; 106:196) is a double blind, randomized, placebo controlled trial which showed that resolution of symptoms was more likely in patients with severe exacerbations who received antibiotics. These findings were confirmed by meta-analyses of multiple trials; however, many of them included trials that were nearly 20 years old. A recent (Respir J. 2009 Feb;33(2):282-8) population based study of 19,000 individuals showed that the treatment of COPD exacerbations with steroids and antibiotics increased the median time to subsequent exacerbation when compared to using steroids alone.
Ann Intern Med 1987; 106:196
Antibiotics Meta Analysis: JAMA 273:957-60 1995
COPD management: Ann Intern Med 2001 Apr 3;134(7):600-20
Cochrane antibiotic analysis: Cochrane Database Syst Rev. 2006 Apr 19;(2):CD004403
Antibiotics reduce subsequent exacerbations: Eur Respir J. 2009 Feb;33(2):282-8


Steroids
The SCCOPE trial is a randomized trial where 271 patients were randomly assigned to IV steroids (2 week vs. 8 week course) vs. placebo. Patient who received steroids had shorter hospital stays and had lower rates of treatment failure at 30 and 90 days. Subsequent meta-analyses confirmed these findings. Further trials were aimed at determining whether oral steroids were equally effective. The authors of a May 2007 article hypothesized that oral corticosteroids would perform just as well as intravenous steroids in the setting of COPD exacerbation requiring hospitalization. They randomized 210 patients to receive a 5 day course of either IV or oral prednisolone (60mg), followed by a 6 day oral taper. All other treatments in the study groups (nebulizer treatments, antibiotics, etc) were identical. The authors found that there was no difference in treatment failure rates (as defined by all-cause mortality, ICU admission, readmission to the hospital, or need to intensify pharmacologic therapy) between the oral and IV steroid groups. The authors therefore conclude that oral corticosteroid therapy is preferred in acute COPD exacerbations, given that it is cheaper and easier to administer. An important limitation to this study is that it excluded patients with “severe” exacerbations (characterized by arterial pH < 7.26, or PaCO2 > 70mmHg), so it is unclear whether the data pertains to this population.
SCCOPE Trial: N Engl J Med 340:1941-7 1999
Cochrane Steroid analysis: Cochrane Database Syst Rev 2005;(1):CD001288
Oral vs. IV steroids: Chest. 2007 Dec;132(6):1741-7. Epub 2007 Jul 23
Oral Steroids: N Engl J Med 2003 Jun 26;348(26):2618-25


Early Non-invasive ventilation
This RCT found that adding pressure support ventilation (i.e. BiPAP) to standard therapy in hypercapneic and mild/moderately acidemic (pH 7.25-7.35) patients with COPD exacerbation significantly reduced need for intubation and in-hospital mortality. The study protocol set the initial inpiratory/expiratory pressure at 10/4 cm H2O and increased as tolerated, and patients were initially maintained on the mask for as long as tolerated on day 1. The amount of time on pressure support ventilation was gradually weaned over next 3 days. The exclusion criteria for this study included patients who were severely acidemic (pH 7.25) and those with poor mental status (GCS8) because an adequate central respiratory drive is required for pressure support ventilation.
Lancet 2000;355:1931-1935


Asthma-inpatient
Expert guidelines
The following link contains the treatment guidelines for acute asthma exacerbations.
www.nhlbi.nih.gov/guidelines/asthma/


Beta Agonists
The cornerstone of treatment for acute asthma exacerbation is inhaled bronchodilators. Beta 2 agonists have been the mainstay of treatment; however the optimal delivery method is unknown. This trial examined the use of nebulized albuterol versus MDI delivery with a spacer. It found that the length of the ED visits were shorter, the total amount of albuterol used was less and there was a greater improvement in peak flow rate with an MDI/spcacer combination as compared with nebulizer.
Albuterol MDI vs. nebs: Chest 2002 Apr;121(4):1036-41


Anticholinergics
The use of anticholinergics remains less clear than inhaled beta agonists. While this trial showed an increase in bronchodilation in patients not having severe exacerbations, other clinical trials showed no benefit to the addition of ipratopium. In fact, the guidelines by the National Asthma Education and Prevention Program Expert Panel III recommend the use of anticholinergics for severe exacerbations in the ED but not hospitalized patients.
Alb and atrovent: Allergy Clin Immunol 1997 Aug;100(2):165-70


Steroids
Patients with moderate or severe Asthma excacerbations should receive steroids. It is unclear what dosing is optimal amongst this patient population. For patients intolerant to oral steroids or with impending respiratory failure, generally IV steroids are used. This trial examined the dose of initial IV steroids which should be used (500 mg vs. 125 mg). There was no difference in outcomes between the two groups.
Steroid dosing: Chest 1995 Jun;107(6):1559-63


Leukotriene inhibitors
Leukotriene inhibitors are used for chronic stable asthma; however, their use in acute exacerbations is unknown. This small trial attempted to address this concern. Patients receiving Zafirlukast were less likely to require hospital admission and had less observation requirements than those patients that did not receive the luekotriene inhibitors. Also, patients were less likely to have a relapse in 28 days if discharged with an oral leukotriene inhibitor. These findings will likely need to be replicated in a larger trial before they are adopted into clinical practice guidelines.
Leukotriene inhibitors: Chest 2004 Nov;126(5):1480-9


Magnesium
The use of IV magnesium is routine in the ED. Despite the lack of evidence, some meta analyses have shown a benefit amongst patients with severe, life threatening exacerbations. Therefore, it is acceptable to use magnesium (with no contraindication) during these circumstances.
IV magnesium failure: Ann Emerg Med 1992 Mar;21(3):260-5
IV magnesium meta analysis: Ann Emerg Med 2000; 36:191
IV magnesium review: Ann Emerg Med 2000; 36:181
CAP
Risk Assesment
Risk assessment while triaging a patient with pneumonia is essential. The pneumonia severity index (PSI) and CURB-65 are two methods to assess a patient for admission.
PSI: N Engl J Med 1997 Jan 23;336(4):243-50
CURB-65: Thorax 2003 May;58(5):377-82


Tx
IV to PO Antibiotics
The early transition from IV to PO antibiotics is fairly well-established in community acquired PNA of mild and moderate severity. This study addresses the effectiveness of switching from IV to PO antibiotics in non-ICU patients with severe PNA (classified by the Pneumonia Severity Index which takes into account age, comorbidities, vital signs, and lab values on presentation). In the intervention arm of the study, patients were switched from IV to PO antibiotics after three days if they met the following criteria for stability: temperature 37.8C (100.0F), SpO2>92%, normal blood pressure, HR100, RR25, absence of mental confusion, and ability to take PO medications. In the control arm of the study patients were maintained on seven days of IV antibiotics. There was no difference in mortality or clinically defined cure and patients who were switched to PO antibiotics had a mean reduction in hospital stay of 1.9 days (CI 0.6-3.2). These criteria for switching from IV to PO antibiotics are similar to the criteria recommended in the 2007 Infectious Disease Society of America guidelines for community acquired PNA.
BMJ 2006;333:1193-1197


Initial ABx for CAP
A study in Chest from 1996 showed that regimens with 2 d. of IV followed by 8 d. of PO antibiotics had the same outcome as regimens with 5 d. IV/5 d. PO or 10 d. IV. Length of stay was significantly shorter in the groups that switched to PO earlier. This study argues for a short course of IV therapy (2 d.) and an early switch to PO antibiotics for earlier discharge.
Arch Int Med 1999;159:2562-2572,
O/P + Prevention
COPD
The GOLD criteria article covers the diagnostic criteria, staging and therapeutic options for COPD patients.
GOLD criteria summary: Am J Respir Crit Care Med Vol 176. pp 532–555; 2007


Risk Assesment
Generally, FEV1 is used to assess risk amongst stable, chronic COPD patients. This trial evaluated the use of simple, clinically available measures to predict death this population. The use of BODE (BMI, obstruction, dyspnea and exercise capacity) was found to have a better predictive value than FEV1 alone.
BODE Index: N Engl J Med 2004; 350:1005


COPD Tx
Short acting bronchodilators
Short acting bronchodilators: Inhaled bronchodilators including short acting beta agonists and anticholinergics have been shown to improve patient outcomes individually. The COMBIVENT trial assessed the use of combination therapy with an inhaled beta agonist and anticholinergic versus beta agonist or anticholinergic alone. Combined therapy was found to increased FEV1 without a change in frequence in exacerbations.
COMBIVENT: Chest 1994; 105:1411


Long acting bronchodilators
Both long acting beta agonists and long acting anticholinergics have been shown to be useful in COPD. The TORCH trial (see below steroid section) highlighted the use of long acting beta agonist salmetrol; however, once daily dosing makes the long acting anticholinergic tiotropium more appealing. The UPLIFT evaluated the use of tiotropium over the course of four years as compared to placebo. It found that there was improved quality of life and less hospitalizations but no decrease in the rate of FEV1 decline.
UPLIFT: N Engl J Med. 2008 Oct 9;359(15):1543-54.


Inhaled steroids
This large RCT took patients with FEV1 60% predicted (Stage IIA or worse) and randomized them to placebo, salmeterol (a long-acting beta agonist) or fluticasone (corticosteroids) alone, or in combination (Advair) with the primary end point of death from any cause. The combination therapy group had a lower risk of death compared to placebo but just missed statistical significance (p = 0.052). Combination therapy was statistically superior to all other interventions in terms of reducing exacerbations and improving spirometric values. Interestingly, combination therapy in comparison with fluticasone alone had statistically significant improvement in mortality. The take-home message is that inhaled corticosteroids should be used in conjunction with inhaled long-acting beta agonist in COPD maintenance therapy because of improved morbidity and possibly improved mortality.
TORCH: N Engl J Med 2007; 356:775-89


Oxygen therapy
Long term oxygen therapy should be used in patients with hypoxemia. It has been shown to improve not only quality of life but also survival in patients with severe COPD and chronic hypoxemia.
NOTT: Ann Intern Med 1980; 93:391


Pulmonary Rehab
Pulmonary rehab is often overlooked as a therapeutic option for patients with COPD. It has been shown to improve quality of life measures, decrease hospitalizations, increase exercise capacity and may decrease mortality.
Rehab: Chest. 2005 Dec;128(6):3799-809
Asthma
Education
This article highlights the utility of education of asthma therapy in the clinic setting to ensure better compliance and outcomes.
Am J Respir Crit Care Med 2003 Nov 1;168(9):1095-9


Expert Panel III Recommendations
These are the recommendations by the expert panel III for the treatment of asthma. The GOAL study evaluated these guidelines in a group of 1500 patients and showed that patients had increased quality of life measures when treated by the NAEPP guidelines. This highlights the stepwise approach to asthma management in the ambulatory setting.
Expert Panel III recs
GOAL: Eur Respir J. 2007 Jan;29(1):56-62. Epub 2006 Oct 18


Pulmonary nodules
This review article discusses the management of the solitary pulmonary nodule.
N Engl J Med 348:2535, June 19, 2003
   
Chapter   5
Renal  
Columbia Nephrology Department Articles
http://columbianephrology.org/

AKI
Acute kidney injury (ARF) is a commonly encountered condition on the wards. As GFR can only be assessed in the steady state, an accurate method for determining renal dysfunction needed to be developed. The RIFLE criteria were adopted to further categorize the level of renal dysfunction and predict outcomes in patients with acute renal dysfunction. Currently, BUN/Cr is the clinical marker used to evaluate acute kidney injury. However, a number of newer and potentially more revealing biomarkers have been developed recently. The review article discusses these biomarkers and their potential application in the clinical setting.
RIFLE: Kidney International (2008) 73, 538–546
AKI Biomarkers: Nephron Clin Pract 2008;109:c192-c197


Electrolyte abnormalities
These articles review the differential diagnosis for both hypo and hypernatremia as well as therapy.
Hyponatremia: N Engl J Med 342:1581, May 25, 2000
Hypernatremia: N Engl J Med 342:1493, May 18, 2000


CIN
Contrast induced nephropathy is a common occurrence with increased use of dye for PCI as well as radiologic procedures. The Mehran score provides a numerical risk of developing CIN using many commonly collected clinical variables. It can be useful when deciding which patients need tests or procedures.
Mehran Score J Am Coll Cardiol. 2004 Oct 6;44(7):1393-9

The prevention of CIN is an area of debate. Multiple trials have been done with saline, bicarbonate and mucomyst. The following trials examine the different therapeutic options and their results.
Volume Expansion: Clin J Am Soc Nephrol. 2008 Jan;3(1):273-80
REMEDIAL: Circulation. 2007 Mar 13;115(10):1211-7
Mucomyst: N Engl J Med. 2000; 343: 180–184


CKD + Anemia
Anemia in CKD is often treated with epoetin and current guidelines advising target hemoglobin range of 11-13.5 are not based on randomized control trials. CHOIR sought to examine differences between patients at both ends of this range, hypothesizing initially that higher hemoglobin would reduce rates of CV events. In actuality, the opposite was true. Patients were those with CKD (GFR15-50), not on HD and with Hbg11 who were randomized to low (10.5-11) or high (13-13.5) groups. Important exclusions were active GI bleed, unstable angina and uncontrolled HTN. Rate of composite events (death, MI, hospitalization for CHF or CVA) was greater in the high Hbg group (17.5% vs. 13.5%, RR 1.34, CI 1.03-1.74) though analysis of individual components showed similar rates between both groups except for a second composite including death and CHF (accounted for 75% of all events) which again was greater in high group. There was no difference in quality of life which was measure by surveys. Also, the study found that the mean dose of epoetin needed to stay at target was two times greater in the high group. There are a lot of flaws in CHOIR including that it was relatively small (1432) with high rates of withdrawal (greater in low group) and not double blinded. But, it does show us to use caution in correcting anemia suggesting that there is no benefit and instead a high cost both financially and with regards to cardiovascular risk. For a succinct editorial see N Engl J Med 2006;355:2144-2146.
EPO for CKD: N Engl J Med 2006; 355: 2085-98


RRT
This article reviews the physiology of renal replacement therapy and provides a good overview of the subject.
Renal Replacement Therapy: Intensive Care Med. 2008 Dec;34(12):2139-46.


O/P + Prevention
CKD (Microalbuminuria)
Microalbuminuria has been linked with adverse outcomes in a number of populations. The following trials are divided by the subpopulation that they were carried out in.
DM-2
For type two diabetics, the ADVANCE trial evaluated the effect of BP lowering and adverse effects. The use of an ACE inhibitor and diuretic to reduce BP was associated with less cardiovascular events and mortality benefit. ACE inhibitors have been shown to reduce the progression of microalbuminuria. The CALM trial illustrates that. The RENAAL trial evaluated the use of ARB instead of ACE and had similar results.
ADVANCE: Lancet. 2007 Sep 8;370(9590):829-40
CALM: N Engl J Med 2001 Sep 20;345(12):870-8
RENAAL: N Engl J Med 2001 Sep 20;345(12):861-9


DM-1
Type 1 diabetics are also at increased risk of adverse events, especially in the setting of poorly controlled sugars. The DCCT trial examined intensive glucose control in this group and showed a decrease in progression of microalbuminuria and adverse events. The EUCLID trial evaluated the treatment of hypertension in this group with an ACE-I and found that albumin excretion decreased with therapy. A recent trial addressed the use of ACE-I amongst normotensive type 1 diabetics. This trial showed that there were no nephroprotective effects; however, there may be benefits to the retinal complications of diabetes.
DCCT: Kidney Int 1995 Jun;47(6):1703-20
EUCLID: Lancet 1997 Jun 21;349(9068):1787-92
Normotensive DM-1: N Engl J Med 361:40, July 2, 2009


CVD
The PREVEND trial highlighted increased cardiovascular risk amongst patients with microalbuminuria. A subsequent study, the PREVEND-IT trial, examined whether treatment with an ACE and statin in patients without hypertension but with microalbuminuria would decrease cardiovascular events.
PREVEND: Circulation 2002 Oct 1;106(14):1777-82
PREVEND-IT: Circulation 2004 Nov 2;110(18):2809-16
   
Chapter   6
Endocrine  
DKA
This review focuses on the diagnosis and treatment of DKA in the inpatient setting.
Am Fam Physician. 2005 May 1;71(9):1705-14


O/P+Prevention
DM
The UKPDS trial was conducted to evaluate the use of glucose lowering with sulfonylureas and insulin versus diet control (conventional treatment at the time). This study showed that there was a reduction in microvascular complications but no reduction in macrovascular complications between the two groups. However, in a follow up study over 10 years, there was a reduction in macrovascular complications in the patients treated with intensive glucose control.
UKPDS 33: Lancet 1998 Sep 12;352(9131):837-53
UKPDS follow up: N Engl J Med. 2008 Oct 9;359(15):1577-89

The ACCORD trial highlights the need for prevention of hyperglycemia amongst patients with type 2 diabetes. The trial was stopped early as there were increased adverse events seen in the intensive glucose lowering arm.
Accord: NEJM Volume 358:2545-2559


Thyroid
These articles highlight management of the thyroid nodule as well as the diagnosis and management of Graves disease.
Thydoid nodule: N Engl J Med 351:1764, October 21, 2004
Graves: N Engl J Med 343:1236, October 26, 2000
   
Chapter   7
Heme/Onc 
DVT PPx
Venous thrombosis and thromboembolism is a frequent complication that our oncology patients encounter, and these patients end up needing long-term anticoagulation. However, oral anticoagulation is always a challenging solution because of its narrow therapeutic window, need for frequent monitoring, and potential drug interactions. This randomized controlled trial by Lee et al. set out to compare oral anticoagulation with warfarin against the low-molecular-weight heparin dalteparin in patients with an active cancer diagnosis and a newly diagnosed, symptomatic proximal DVT or PE. It was a relatively large study (336 patients in each group), and the authors were able to obtain a statistically significant risk reduction for recurrent venous thromboembolism with dalteparin vs. warfarin. In addition, there was no significant difference in bleeding complications between the two groups. They were unable, however, to demonstrate a mortality benefit, as most patients who passed died of progressive disease. Nonetheless, this study offered a more efficacious and arguably more viable method of anticoagulation for cancer patients with DVT/PE. The questions and controversy it raised (mostly re: cost-effectiveness, ease of use, and clinically significant incidence of HIT) have largely been put to rest. The study used dalteparin 200 IU/kg for a treatment course of 6 months. Here at CUMC, we use enoxaparin 1mg/kg BID or 1.5mg/kg daily, which is presumed to have comparable efficacy with dalteparin.
Lovenox for DVT in Cancer patients: N Engl J Med 2003;349:146-153


HITT
Heparin-induced thrombocytopenia (HIT) carries a high risk of thrombosis and mortality, and requires anticoagulant therapy to reduce these risks. This 2001 study established argatroban, a direct thrombin inhibitor, as one of the anticoagulants of choice in patients with HIT. The study enrolled 304 adults with either isolated HIT or HITTS (HIT with thrombosis syndrome). Because all patients were treated with argatroban, there was no placebo arm (a placebo arm was deemed unethical, since it was already known that simply discontinuing heparin was not sufficient treatment for HIT/HITTS). Instead, they compared study patients with historical controls-- i.e., patients who developed HIT before the advent of direct thrombin inhibitors, and who were therefore managed with the standard of care at that time: heparin discontinuation +/- oral anticoagulation. The study found that argatroban therapy significantly reduced the incidence of all-cause mortality, all-cause amputation, and new thrombosis (treated as a composite endpoint) in patients with HIT compared to historical controls. Bleeding rates were found to be similar between the two groups
Argatroban for HITT: Circulation 2001;103:1838-1843


Onc emergencies
GCSF for neuropenic fever
Febrile neutropenia is sometimes referred to as an “oncologic emergency.” Indeed, it can carry significant morbidity and mortality, and certainly constitutes a large portion of our inpatient admissions here at CPMC. While the role of early antibiotics is well-established and crucial, adjunctive therapies including hematopoietic colony stimulating factors are more controversial. The current study aims to address this controversy. As febrile neutropenic patients are not a homogeneous group (e.g., there is a preponderance of data suggesting that low-risk patients should be treated in an outpatient setting), this study focused on the high risk category (risk factors including sepsis & poor performance status). In this multicenter randomized trial of 210 patients, the authors show that the addition of G-CSF to an antibiotic regimen for patients with fever and neutropenia leads not only to shorter duration of neutropenia, but also to reduced hospital stay and possibly to reduced costs as well. This is a very limited study however - it was open-label, unblinded, and not placebo-controlled. Patients with leukemia & those undergoing myeloablative chemotherapy were excluded as well. Mortality was similar in both the control and experimental group. Nonetheless, the study does provide support for the administration of G-CSF to high-risk solid tumor patients with fever and neutropenia. For a good Cochrane review on this literature, see Journal of Clinical Oncology 2005;23:4198-4214.
GCSF for neutropenic fever: J Natl Cancer Inst 2001;93:31-38


Hypercalcemia
Hypercalcemia of malignancy (HCM) is another syndrome that is often referred to an oncologic emergency. It is common in cancer patients, occurring in approximately 10-20% of cases. Bisphosphonates are the most commonly used agents to treat hypercalcemia of malignancy and in addition, may prevent skeletal complications. Which bisphosphonate should be used as the first line of defense and what is the data behind its efficacy and safety? In this article, the authors used two identical, concurrent, parallel, multicenter, randomized, double-blind, double-dummy trials to compare the efficacy and safety of zoledronic acid and pamidronate for treating hypercalcemia of malignancy. Patients with moderate to severe HCM [> or = 12.0 mg/dL] were treated with a single dose of zoledronic acid (4 or 8 mg) via 5-minute infusion or pamidronate (90 mg) via 2-hour infusion. Clinical end points included rate of complete response by day 10, response duration, and time to relapse. 287 patients were randomized and evaluated for safety; 275 were evaluated for efficacy. Both doses of zoledronic acid were superior to pamidronate in the treatment of HCM. The complete response rates by day 10 were 88.4% (P = .002), 86.7% (P = .015), and 69.7% for zoledronic acid 4 mg and 8 mg and pamidronate 90 mg, respectively. Normalization of CSC occurred by day 4 in approximately 50% of patients treated with zoledronic acid and in only 33.3% of the pamidronate-treated patients. The median duration of complete response favored zoledronic acid 4 and 8 mg over pamidronate 90 mg with response durations of 32, 43, and 18 days, respectively. Conclusion: Zoledronic acid is superior to pamidronate; 4 mg is the dose recommended for initial treatment of HCM and 8 mg for relapsed or refractory hypercalcemia.
Zometa vs. Pamidronate: J Clin Oncol 2001;19:558-567
O/P + Prevention
   
Chapter   8
Neurology 
Stroke
Thrombolysis
These studies established the use of TPA in acute stroke. The benefit seen within the first three house in NINDS has now been expanded to 4.5 hours due to the findings of the ECASS 3 trial.
NINDS N Engl J Med 1995 Dec 14;333(24):1581-7
ECASS 3: N Engl J Med. 2008 Sep 25;359(13):1317-29


ASA
Secondary prevention with antiplatelet agents has long been the standard of care for patients with CVA. These trials evaluate the different treatment regiments. ASA has had proven benefit for many years; however the CHARISMA trial shows that ASA and plavix may have increased bleeding events.
ATT ASA analysis: BMJ 2002 Jan 12;324(7329):71-86
CHARISMA -N Engl J Med. 2006 Apr 20;354(16):1706-17


Dypiridamole
The use of dypiridamole (aggrenox) has been evaluated with the following trials. In the ESPRIT study, which was a randomized controlled trial, the authors assigned patients to aspirin (30-325 mg daily) with (n=1363) or without (n=1376) dipyridamole (200 mg twice daily) within 6 months of a transient ischemic attack or minor stroke of presumed arterial origin. The primary outcome event was composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction, or major bleeding complication, whichever happened first. Mean follow-up in this study was 3.5 years. Primary outcome events arose in 173 (13%) patients on aspirin and dipyridamole and in 216 (16%) on aspirin alone (hazard ratio 0.80, 95% CI 0.66-0.98; absolute risk reduction 1.0% per year, 95% CI 0.1-1.8). Addition of the ESPRIT data to the meta-analysis of previous trials resulted in an overall risk ratio for the composite of vascular death, stroke, or myocardial infarction of 0.82 (95% CI 0.74-0.91). Patients on aspirin and dipyridamole discontinued trial medication more often than those on aspirin alone (470 vs. 184), mainly because of headache. The ESPRIT results provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after CVA.
ESPRIT: Lancet 2006;367:1665-1673

ESPS-2 evaluated the use of ASA and dypiridamole versus both components alone and placebo. The study showed that the combination of ASA and dypiridamole was more effective than placebo and either component alone.
ESPS 2: J Neurol Sci 1996 Nov;143(1-2):1-13

The PROFESS trial showed that plavix and ASA+dypiridamole had similar risks and benefits in the secondary prevention of stroke.
PROFESS- N Engl J Med. 2008 Sep 18;359(12):1238-51

Statin
The SPARCL trial evaluated the use of intensive lipid lowering after stroke or TIA in patients with no known CVD. There was a significant reduction in all cardiovascular endpoints including stroke and TIA.
SPARCL- N Engl J Med. 2006 Aug 10;355(6):549-59
   
Chapter   9
Med Consult 
Med consult EBM website (Username: computer Password: monitor)
http://www.hospitalist.cumc.columbia.edu/access/med_con_ebm.htm


Pre-Op articles
Revised cardiac index
The Goldman revised cardiac index is used to assess cardiovascular risk prior to non-cardiac surgery. The following article explains the criteria and its use amongst a large population of individuals.
Goldman Index-Circulation 1999 Sep 7;100(10):1043-9


Beta blocker
The use of beta blockers remains controversial prior to surgery. The POISE trial assigned patients at cardiovascular risk to receive fixed dose metoprolol prior to non cardiac surgery. While cardiovascular death was decreased in the group receiving metoprolol, total mortality was increased and significant hypotension occurred in the group receiving metoprolol.
POISE Lancet. 2008 May 31;371(9627):1839-47


Revascularization
The CARP trial tried to address the use of revascularization prior to procedures. In patients that underwent angiography, those without high risk features did not benefit from revascularization prior to surgery.
CARP- N Engl J Med 2004 Dec 30;351(27):2795-804
Hip Replacement
This article examines the perioperative management of hip replacements.
Ann Intern Med 128:1010-20 1998


Oral anticoagulants
This article examines the perioperative management of patients on oral anticoagulation prior to surgery.
Arch Intern Med 163:901-8 2003
   
Chapter  10
ID
General ID
Steroids for meningitis
This randomized, double-blind study of 301 patients compares dexamethasone (10mg q6 x4 days) to placebo when given with or before the initiation of IV antibiotics for bacterial meningitis. The study shows that patients who received dexamethasone had a statistically significant improvement in the study’s primary endpoint, a Glasgow Outcome Scale score of 5 (little or no neurologic disability). They also had a statistically significant mortality benefit (secondary endpoint). Subgroup analysis shows that the patients with improved Glasgow Outcome Scale and mortality were those with S. pneumoniae isolated from their CSF and those with a GCS of 8-11 on presentation. As a result of this study (and a subsequent meta-analysis by the same author: Lancet Infectious Disease 2004;4:139) dexamethasone is usually recommended for adults with bacterial meningitis and a GCS of 8-11 on presentation. Using dexamethasone in patients with a GCS above and below this range is more controversial. The Infectious Disease Society of America 2004 guidelines for the treatment of bacterial meningitis actually recommend using dexamethasone regardless of the GCS because of the worry that GCS assessment would delay the initiation of antibiotics. If culture and/or gram stain is consistent with a non-pneumococcal bacterial meningitis, this study shows that there is no statistically significant benefit to continuing dexamethasone. Further studies are needed to more completely assess the use of dexamethasone in immunocompromised patients and in patients with nonpneumococcal meningitis.
N Engl J Med 2002;347;1549-1556


Double coverage for psuedomonas
The use of double coverage for the treatment of pseudomonal infections remains controversial. The following reviews look at the current evidence and examine which patients benefit more from receiving coverage with two agents.
Double Coverage Review: BMJ 2004 Mar 20;328(7441):668
Double Coverage for Bacteremia: Lancet Infect Dis 2004 Aug;4(8):519-27


Vanco vs. Flagyl for C.Diff
C. difficile infection is an increasing common cause of diarrhea, and vancomycin and metronidazole have both proven to have efficacy in its treatment. The study compares PO metronidazole with PO vancomycin in patients with C. diff infection stratified by disease severity. Patients were excluded if they had life-threatening complications or prior treatment with one of the study drugs. The study compared two subgroups: those with mild and severe C. diff (stratified by a point scale dependent on age, temperature, albumin, and WBC count). The primary outcome was clinical cure, defined as resolution of diarrhea within six days and negative C. diff toxin on days six and ten. For mild disease, clinical cure was achieved in 90% of patients on PO metronidazole and 98% of patients on PO vancomycin (p=.36). For severe disease, clinical cure was achieved in 76% of patients on PO metronidazole and 97% of patients on PO vancomycin (p=.02). This study provides evidence to support using vancomycin only in severe disease and it is the basis for the C. difficile treatment guidelines issued by the Division of Infectious Diseases at CUMC (available through http://www.cumc.columbia.edu/dept/id/clinical_references.html). Our guidelines use a very similar point scale for stratification of disease severity and recommend metronidazole for more mild disease and vancomycin (+/-metronidazole) for more severe infection.
CID 2007;45:302-307
AIDS/TB
OI PPx
This article reviews prophylaxis for patients with HIV/AIDS to prevent opportunistic infections.
OI PPx: N Engl J Med 342:1416-29 2000


Steroids for PCP
PCP (actually Pneumocystis jiroveci pneumonia) in patients with AIDS is historically associated with a high mortality. There have been many small studies whish show the benefit of adjunctive steroids in patients with severe PCP and a Cochrane meta-analysis of six studies and a meta-analysis strengthens this data (Briel et al. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV-infection. Cochrane Database of Systemic Reviews 2006, Issue 3). One of the primary studies in this review is included here. The trial is randomized but not blinded and the patients were stratified according to severity using the hypoxemia ratio (PaO2/FiO2). The study shows a reduction in respiratory failure and death in patients with a PaO2/FiO2 ratio of 350 or less. The Cochrane review, which did not include patients with PaO270 or A-a gradient 35, showed a mortality benefit to steroid use, with a NNT of 9.
Steroids for PCP: N Engl J Med 1990;323:1451-1457


HAART in acute setting
The optimal time to initiate antiretrovirals in asymptomatic HIV patients is unclear. Current guidelines suggest starting treatment when the CD4+ count reaches 350, although there is minimal data from RCT’s to support this. In this multi-center observational study, patients with CD4+ counts of >500 and CD4+ counts of 350-500 were considered separately. Subjects in both groups were grouped based upon whether they initiated antiretroviral treatment within 6 months of entry into the study or initiated treatment after their CD4+ count fell below the threshold (500 in the first group, 350 in the second group). Among the group who started with CD4+ of 350-500, waiting until the CD4+ count fell below 350 was associated with a 69% increase in the relative risk of death within 1 year, the primary outcome. In the group with >500 CD4+ cells at the outset, deferring therapy until falling below 500 CD4+ cells was associated with a 94% increased risk of death. The major strengths of this trial include its large size and its use of all-cause mortality as an endpoint. There are several potential limitations, including significant baseline differences between the two groups, such as higher rates of Hep C co-infection and higher rates of IVDU in the deferred-therapy group (although these were adjusted for). Appropriately accounting for such differences will require an RCT.
Early ARVs: N Engl J Med 2009;360:1815-26)


O/P+Prevention
These articles deal with the increasing incidence of community acquired MRSA infections and the use of the pneumonia vaccine in the elderly patients.
Comm acquired MRSA: N Engl J Med 2005;352:1436-44.
Pneumonia vaccine: N Engl J Med 348:1747-55 2003


   
Chapter  11
EBM
   
Index
Website

Capter 1 --- CCU

     Virtual CCU link
     Cardiogenic Shock
     PA Catheters
     Arrests


Capter 2 --- Cardiology
     CHF
          Biomarkers
              
 Review
          B-blocker
          ACE-I/ARBs
          Bi-dil
          Aldo blockers
          Digoxin
          AICD
          BiV pacing
          Normal EF

     
ACS
          Heparin
          ASA
          Statin
          Plavix
          B-blockers
          Bivalirudin
          IIB/IIIA inhibitors: for STEMI/PCI
          Thrombolysis/PCI
          Other Causes of ST Elevations
          Clinical Decision-Risk Assesment

     Arrhythmia
          A-fib
          Brugada
          BMJ EKG articles

     
O/P + Prevention
          ASA for primary prevention
          AAA screening
          HTN-Hyperlipidemia
          PAD: Review

Capter 3 --- GI
     GI bleed
          UGI bleeds
               
Variceal bleeds
                    
Beta blockers
                    Somatostatin analogs/Terlipressin

          LGI-c-scope

     
Pancreatitis
          Antibiotics
          Feeds
          BISAP
          Early ERCP

    
 Liver
          LFT abnormalities
          Acute Liver Failure
          Cirrhosis
             
   Review
          Alcoholic Hepatitis
          SBP
           
    Norfloxacin
     O/P + Prevention
          HBV/HCV
          Diarrhea
          Colon CA screening


Capter 4 --- Pulmonary
     MICU
          MICU curriculum
          CVP Monitoring
          Surviving Sepsis Campaign

  
   PE
          Clinical Decision making

    
 COPD-inpatient
          ATS clinical guidelines
          Antibiotics
          Steroids
          Early Non-invasive ventilation

     
Asthma-inpatient
          Expert guidelines
          Beta Agonists
          Anticholinergics
          Steroids
          Leukotriene inhibitors
          Magnesium

     
CAP
          Risk Assesment
          Tx
              
 IV to PO Antibiotics
               Initial ABx for CAP


     
O/P + Prevention
          COPD
            
   Risk Assesment
               COPD Tx

                    
Short acting bronchodilators
                    Long acting bronchodilators
                    Inhaled steroids
                    Oxygen therapy
                    Pulmonary Rehab

         
 Asthma
            
   Education
               Expert Panel III Recommendations

          Pulmonary nodules


Capter 5 --- Renal
     AKI
     Electrolyte abnormalities
     CIN
     CKD + Anemia
     RRT
     O/P + Prevention

          
CKD (Microalbuminuria)
              
 DM-2
               DM-1
               CVD


Capter 6 --- Endocrine
     DKA
     O/P+Prevention

          
DM
          Thyroid


Capter 7 --- Heme/Onc
     DVT PPx
     HITT
     Onc emergencies

          
GCSF for neuropenic fever
          Hypercalcemia

     
O/P + Prevention

Capter 8 --- Neurology
     Stroke
          
Thrombolysis
          ASA
          Dypiridamole
          Statin


Capter 9 --- Med Consult 
     Pre-Op articles
          
Revised cardiac index
          Beta blocker
          Revascularization

   
  Hip Replacement
     Oral anticoagulants

Capter 10 --- ID
     General ID
         
 Steroids for meningitis
          Double coverage for psuedomonas
          Vanco vs. Flagyl for C.Diff

     
AIDS/TB
         
 OI PPx
          Steroids for PCP
          HAART in acute setting

     
O/P+Prevention

Capter 11 --- EBM     
     EBM links
 
History
Website History

Welcome to Readings in Internal Medicine!

This website is maintained by residents of the Department of Medicine at Columbia University Medical Center. Founded in 2003 by Juliet Jacobsen, MD, the Readings in Internal Medicine (RIM) site was designed to provide Columbia's medical housestaff with a portable, easy-to-navigate, up-to-date, and dynamic foundation of primary sources that address clinical questions commonly encountered on the wards and in clinic.

The website is divided into medical subspecialties which are, in turn, subdivided into areas of clinical interest. While the bulk of the content consists of randomized clinical trials, the site also includes classic case series and review articles that residents have found particularly helpful. Certain crucial studies are accompanied by commentary by the resident-editors. The syllabi of several hospital ward rotations can be accessed on the site as well.

We hope that you find RIM a helpful addition to your education and clinical armamentarium. If you have suggestions related to the site's design or content, please email the editor,
Nishant Verma or Webmaster
 
   
 
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