A Comprehensive Care Management Program to Prevent Chronic Obstructive Pulmonary Disease Hospitalizations: A Randomized, Controlled Trial.

Ann Intern Med. 2012 May 15;156(10):673-683

Authors: Fan VS, Gaziano JM, Lew R, Bourbeau J, Adams SG, Leatherman S, Thwin SS, Huang GD, Robbins R, Sriram PS, Sharafkhaneh A, Mador MJ, Sarosi G, Panos RJ, Rastogi P, Wagner TH, Mazzuca SA, Shannon C, Colling C, Liang MH, Stoller JK, Fiore L, Niewoehner DE

Abstract
Background: Improving a patient's ability to self-monitor and manage changes in chronic obstructive pulmonary disease (COPD) symptoms may improve outcomes. Objective: To determine the efficacy of a comprehensive care management program (CCMP) in reducing the risk for COPD hospitalization. Design: A randomized, controlled trial comparing CCMP with guideline-based usual care. (ClinicalTrials.gov registration number: NCT00395083) Setting: 20 Veterans Affairs hospital-based outpatient clinics. Participants: Patients hospitalized for COPD in the past year. Intervention: The CCMP included COPD education during 4 individual sessions and 1 group session, an action plan for identification and treatment of exacerbations, and scheduled proactive telephone calls for case management. Patients in both the intervention and usual care groups received a COPD informational booklet; their primary care providers received a copy of COPD guidelines and were advised to manage their patients according to these guidelines. Patients were randomly assigned, stratifying by site based on random, permuted blocks of variable size. Measurements: The primary outcome was time to first COPD hospitalization. Staff blinded to study group performed telephone-based assessment of COPD exacerbations and hospitalizations, and all hospitalizations were blindly adjudicated. Secondary outcomes included non-COPD health care use, all-cause mortality, health-related quality of life, patient satisfaction, disease knowledge, and self-efficacy. Results: Of the eligible patients, 209 were randomly assigned to the intervention group and 217 to the usual care group. Citing serious safety concerns, the data monitoring committee terminated the intervention before the trial's planned completion after 426 (44%) of the planned total of 960 patients were enrolled. Mean follow-up was 250 days. When the study was stopped, the 1-year cumulative incidence of COPD-related hospitalization was 27% in the intervention group and 24% in the usual care group (hazard ratio, 1.13 [95% CI, 0.70 to 1.80]; P = 0.62). There were 28 deaths from all causes in the intervention group versus 10 in the usual care group (hazard ratio, 3.00 [CI, 1.46 to 6.17]; P = 0.003). Cause could be assigned in 27 (71%) deaths. Deaths due to COPD accounted for the largest difference: 10 in the intervention group versus 3 in the usual care group (hazard ratio, 3.60 [CI, 0.99 to 13.08]; P = 0.053). Limitations: Available data could not fully explain the excess mortality in the intervention group. Ability to assess the quality of the educational sessions provided by the case managers was limited. Conclusion: A CCMP in patients with severe COPD had not decreased COPD-related hospitalizations when the trial was stopped prematurely. The CCMP was associated with unanticipated excess mortality, results that differ markedly from similar previous trials. A data monitoring committee should be considered in the design of clinical trials involving behavioral interventions. Primary Funding Source: Veterans Affairs Cooperative Study Program.

PMID: 22586006 [PubMed - as supplied by publisher]

Hospital strategies for reducing risk-standardized mortality rates in acute myocardial infarction.

Ann Intern Med. 2012 May 1;156(9):618-26

Authors: Bradley EH, Curry LA, Spatz ES, Herrin J, Cherlin EJ, Curtis JP, Thompson JW, Ting HH, Wang Y, Krumholz HM

Abstract
Background: Despite recent improvements in survival after acute myocardial infarction (AMI), U.S. hospitals vary 2-fold in their 30-day risk-standardized mortality rates (RSMRs). Nevertheless, information is limited on hospital-level factors that may be associated with RSMRs. Objective: To identify hospital strategies that were associated with lower RSMRs. Design: Cross-sectional survey of 537 hospitals (91% response rate) and weighted multivariate regression by using data from the Centers for Medicare & Medicaid Services to determine the associations between hospital strategies and hospital RSMRs. Setting: Acute care hospitals with an annualized AMI volume of at least 25 patients. Participants: Patients hospitalized with AMI between 1 January 2008 and 31 December 2009. Measurements: Hospital performance improvement strategies, characteristics, and 30-day RSMRs. Results: In multivariate analysis, several hospital strategies were significantly associated with lower RSMRs and in aggregate were associated with clinically important differences in RSMRs. These strategies included holding monthly meetings to review AMI cases between hospital clinicians and staff who transported patients to the hospital (RSMR lower by 0.70 percentage points), having cardiologists always on site (lower by 0.54 percentage points), fostering an organizational environment in which clinicians are encouraged to solve problems creatively (lower by 0.84 percentage points), not cross-training nurses from intensive care units for the cardiac catheterization laboratory (lower by 0.44 percentage points), and having physician and nurse champions rather than nurse champions alone (lower by 0.88 percentage points). Fewer than 10% of hospitals reported using at least 4 of these 5 strategies. Limitation: The cross-sectional design demonstrates statistical associations but cannot establish causal relationships. Conclusion: Several strategies, which are currently implemented by relatively few hospitals, are associated with significantly lower 30-day RSMRs for patients with AMI. Primary Funding Source: The Agency for Healthcare Research and Quality, the United Health Foundation, and the Commonwealth Fund.

PMID: 22547471 [PubMed - in process]

New fibrate use and acute renal outcomes in elderly adults: a population-based study.

Ann Intern Med. 2012 Apr 17;156(8):560-9

Authors: Zhao YY, Weir MA, Manno M, Cordy P, Gomes T, Hackam DG, Juurlink DN, Mamdani M, Moist L, Parikh CR, Paterson JM, Wald R, Yao Z, Garg AX

Abstract
Background: Fibric acid derivatives (fibrates) have been shown to increase serum creatinine level in randomized trials. Objective: To assess renal outcomes in elderly adults within 90 days of a new fibrate prescription. Design: Population-based cohort study. Setting: Ontario, Canada. Patients: Patients aged 66 years or older with a new outpatient prescription for a fibrate or ezetimibe (comparator drug) between January 2004 and December 2008. Measurements: Hospitalization for an increase in serum creatinine level (primary outcome) and consultation with a nephrologist, receipt of dialysis for severe acute kidney injury, all-cause mortality, and increases in serum creatinine level (secondary outcomes). All outcomes were assessed within 90 days of a new prescription for ezetimibe or a fibrate. Results: Compared with ezetimibe users (n = 61 831), fibrate users (n = 19 072) were more likely to be hospitalized for an increase in serum creatinine level (adjusted odds ratio, 2.4 [95% CI, 1.7 to 3.3]) and were more likely to consult a nephrologist (absolute risk difference, 0.15% [CI, 0.01% to 0.29%]; adjusted odds ratio, 1.3 [CI, 1.0 to 1.6]). There were no differences between groups in the risk for all-cause mortality or receiving dialysis for severe acute kidney injury. In a subpopulation of 1110 patients (fibrates, n = 220; ezetimibe, n = 890), 9.1% of fibrate users and 0.3% of ezetimibe users had an increase in serum creatinine level of 50% or more (absolute difference, 8.8% [CI, 4.5% to 13.1%]; odds ratio, 29.6 [CI, 8.7 to 100.5]). Risks were greater among fibrate users with chronic kidney disease. Limitations: Because hospitalizations for an increase in serum creatinine level were underestimated, absolute differences may be misleading. Most patients (91%) were prescribed fenofibrate. Serum creatinine levels were measured as part of routine care and were not available for everyone or at predefined times. Conclusion: New fibrate use in elderly adults was associated with an increase in serum creatinine level and a small 90-day absolute increase in hospitalizations and nephrologist consultations. There was no detectable effect on dialysis for severe acute kidney injury or on mortality. The mechanism and clinical significance of the increase in serum creatinine level with fibrates is unclear. Primary Funding Source: Ontario Ministry of Health and Long-Term Care Drug Innovation Fund.

PMID: 22508733 [PubMed - in process]

Effects of Antiplatelet Therapy on Mortality and Cardiovascular and Bleeding Outcomes in Persons With Chronic Kidney Disease: A Systematic Review and Meta-analysis.

Ann Intern Med. 2012 Mar 20;156(6):445-59

Authors: Palmer SC, Di Micco L, Razavian M, Craig JC, Perkovic V, Pellegrini F, Copetti M, Graziano G, Tognoni G, Jardine M, Webster A, Nicolucci A, Zoungas S, Strippoli GF

Abstract
Background: Antiplatelet agents are used to prevent cardiovascular events; however, treatment effects may differ in persons with chronic kidney disease (CKD) because atherosclerotic disease is less prevalent, whereas bleeding hazards may be increased in this population. Purpose: To summarize the effects of antiplatelet treatment on cardiovascular events, mortality, and bleeding in persons with CKD. Data Sources: Embase and Cochrane databases through November 2011 without language restriction. Study Selection: Randomized trials that included adults with CKD and compared antiplatelet agents with standard care, placebo, or no treatment. Data Extraction: Data for populations, interventions, outcomes, and risk for bias were extracted. Quality of evidence for treatment effects on myocardial infarction, death, and bleeding was summarized by using Grading of Recommendations Assessment, Development, and Evaluation guidelines. Data Synthesis: Nine trials (all post hoc subgroup analyses for CKD) involving 9969 persons who had acute coronary syndromes or were undergoing percutaneous coronary intervention and 31 trials involving 11 701 persons with stable or no cardiovascular disease were identified. Low-quality evidence has found that in persons with acute coronary syndromes, glycoprotein IIb/IIIa inhibitors or clopidogrel plus standard care compared with standard care alone had little or no effect on all-cause or cardiovascular mortality or on myocardial infarction but increased serious bleeding. Compared with placebo or no treatment in persons with stable or no cardiovascular disease, antiplatelet agents prevented myocardial infarction but had uncertain effects on mortality and increased minor bleeding according to generally low-quality evidence. Limitations: Data for antiplatelet agents in persons with CKD are frequently derived from post hoc analyses of trials of broader populations. Definitions for bleeding outcomes and trial duration were heterogeneous. Conclusion: Benefits for antiplatelet therapy among persons with CKD are uncertain and are potentially outweighed by bleeding hazards. Primary Funding Source: None.

PMID: 22431677 [PubMed - in process]

Evaluation of newer risk markers for coronary heart disease risk classification: a cohort study.

Ann Intern Med. 2012 Mar 20;156(6):438-44

Authors: Kavousi M, Elias-Smale S, Rutten JH, Leening MJ, Vliegenthart R, Verwoert GC, Krestin GP, Oudkerk M, de Maat MP, Leebeek FW, Mattace-Raso FU, Lindemans J, Hofman A, Steyerberg EW, van der Lugt A, van den Meiracker AH, Witteman JC

Abstract
Background: Whether newer risk markers for coronary heart disease (CHD) improve CHD risk prediction remains unclear. Objective: To assess whether newer risk markers for CHD risk prediction and stratification improve Framingham risk score (FRS) predictions. Design: Prospective population-based study. Setting: The Rotterdam Study, Rotterdam, the Netherlands. Participants: 5933 asymptomatic, community-dwelling participants (mean age, 69.1 years [SD, 8.5]). Measurements: Traditional CHD risk factors used in the FRS (age, sex, systolic blood pressure, treatment of hypertension, total and high-density lipoprotein cholesterol levels, smoking, and diabetes) and newer CHD risk factors (N-terminal fragment of prohormone B-type natriuretic peptide levels, von Willebrand factor antigen levels, fibrinogen levels, chronic kidney disease, leukocyte count, C-reactive protein levels, homocysteine levels, uric acid levels, coronary artery calcium [CAC] scores, carotid intima-media thickness, peripheral arterial disease, and pulse wave velocity). Results: Adding CAC scores to the FRS improved the accuracy of risk predictions (c-statistic increase, 0.05 [95% CI, 0.02 to 0.06]; net reclassification index, 19.3% overall [39.3% in those at intermediate risk, by FRS]). Levels of N-terminal fragment of prohormone B-type natriuretic peptide also improved risk predictions but to a lesser extent (c-statistic increase, 0.02 [CI, 0.01 to 0.04]; net reclassification index, 7.6% overall [33.0% in those at intermediate risk, by FRS]). Improvements in predictions with other newer markers were marginal. Limitation: The findings may not be generalizable to younger or nonwhite populations. Conclusion: Among 12 CHD risk markers, improvements in FRS predictions were most statistically and clinically significant with the addition of CAC scores. Further investigation is needed to assess whether risk refinements using CAC scores lead to a meaningful change in clinical outcome. Whether to use CAC score screening as a more routine test for risk prediction requires full consideration of the financial and clinical costs of performing versus not performing the test for both persons and health systems. Primary Funding Source: Netherlands Organization for Health Research and Development (ZonMw).

PMID: 22431676 [PubMed - in process]

Long-Term Efficacy of Dapagliflozin in Patients With Type 2 Diabetes Mellitus Receiving High Doses of Insulin: A Randomized Trial.

Ann Intern Med. 2012 Mar 20;156(6):405-415

Authors: Wilding JP, Woo V, Soler NG, Pahor A, Sugg J, Rohwedder K, Parikh S,

Abstract
Background: Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2, may improve glycemic control with a lower dose of insulin and attenuate the associated weight gain in patients with inadequate control despite high doses of insulin. Objective: To evaluate the efficacy and safety of adding dapagliflozin therapy in patients whose type 2 diabetes mellitus is inadequately controlled with insulin with or without oral antidiabetic drugs. Design: A 24-week, randomized, placebo-controlled, multicenter trial followed by a 24-week extension period. An additional 56-week extension period is ongoing. (ClinicalTrials.gov registration number: NCT00673231) Setting: 126 centers in Europe and North America from 30 April 2008 to 19 November 2009. Patients: 808 patients with inadequately controlled type 2 diabetes mellitus receiving at least 30 U of insulin daily, with or without up to 2 oral antidiabetic drugs. Intervention: Patients were randomly assigned in a 1:1:1:1 ratio and allocated with a computer-generated scheme to receive placebo or 2.5, 5, or 10 mg of dapagliflozin, once daily, for 48 weeks. Measurements: The primary outcome was change in hemoglobin A(1c) from baseline to 24 weeks. Secondary outcomes included changes in body weight, insulin dose, and fasting plasma glucose level at 24 weeks and during the 24-week extension period. Adverse events were evaluated throughout both 24-week periods. Results: 800 patients were analyzed. After 24 weeks, mean hemoglobin A(1c) decreased by 0.79% to 0.96% with dapagliflozin compared with 0.39% with placebo (mean difference, -0.40% [95% CI, -0.54% to -0.25%] in the 2.5-mg group, -0.49% [CI, -0.65% to -0.34%] in the 5-mg group, and -0.57% [CI, -0.72% to -0.42%] in the 10-mg group). Daily insulin dose decreased by 0.63 to 1.95 U with dapagliflozin and increased by 5.65 U with placebo (mean difference, -7.60 U [CI, -10.32 to -4.87 U] in the 2.5-mg group, -6.28 U [CI, -8.99 to -3.58 U] in the 5-mg group, and -6.82 U [CI, -9.56 to -4.09 U] in the 10-mg group). Body weight decreased by 0.92 to 1.61 kg with dapagliflozin and increased by 0.43 kg with placebo (mean differences, -1.35 kg [CI, -1.90 to -0.80 kg] in the 2.5-mg group, -1.42 kg [CI, -1.97 to -0.88 kg] in the 5-mg group, and -2.04 kg [CI, -2.59 to -1.48 kg] in the 10-mg group). These effects were maintained at 48 weeks. Compared with the placebo group, patients in the pooled dapagliflozin groups had a higher rate of hypoglycemic episodes (56.6% vs. 51.8%), events suggesting genital infection (9.0% vs. 2.5%), and events suggesting urinary tract infection (9.7% vs. 5.1%). Limitation: Insulin doses were not titrated to target, and the study was not designed to evaluate long-term safety. Conclusion: Dapagliflozin improves glycemic control, stabilizes insulin dosing, and reduces weight without increasing major hypoglycemic episodes in patients with inadequately controlled type 2 diabetes mellitus. Primary Funding Source: AstraZeneca and Bristol-Myers Squibb.

PMID: 22431673 [PubMed - as supplied by publisher]

Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline From the American College of Physicians.

Ann Intern Med. 2012 Feb 7;156(3):218-231

Authors: Qaseem A, Humphrey LL, Sweet DE, Starkey M, Shekelle P,

Abstract
Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness and safety of type 2 diabetes medications. Methods: This guideline is based on a systematic evidence review evaluating literature published on this topic from 1966 through April 2010 that was identified by using MEDLINE (updated through December 2010), EMBASE, and the Cochrane Central Register of Controlled Trials. Searches were limited to English-language publications. The clinical outcomes evaluated for this guideline included all-cause mortality, cardiovascular morbidity and mortality, cerebrovascular morbidity, neuropathy, nephropathy, and retinopathy. This guideline grades the evidence and recommendations by using the American College of Physicians clinical practice guidelines grading system. Recommendation 1: ACP recommends that clinicians add oral pharmacologic therapy in patients diagnosed with type 2 diabetes when lifestyle modifications, including diet, exercise, and weight loss, have failed to adequately improve hyperglycemia (Grade: strong recommendation; high-quality evidence). Recommendation 2: ACP recommends that clinicians prescribe monotherapy with metformin for initial pharmacologic therapy to treat most patients with type 2 diabetes (Grade: strong recommendation; high-quality evidence). Recommendation 3: ACP recommends that clinicians add a second agent to metformin to treat patients with persistent hyperglycemia when lifestyle modifications and monotherapy with metformin fail to control hyperglycemia (Grade: strong recommendation; high-quality evidence).

PMID: 22312141 [PubMed - as supplied by publisher]

Estimating Equations for Glomerular Filtration Rate in the Era of Creatinine Standardization: A Systematic Review.

Ann Intern Med. 2012 Feb 6;

Authors: Earley A, Miskulin D, Lamb EJ, Levey AS, Uhlig K

Abstract
Background: Clinical laboratories are increasingly reporting estimated glomerular filtration rate (GFR) by using serum creatinine assays traceable to a standard reference material. Purpose: To review the performance of GFR estimating equations to inform the selection of a single equation by laboratories and the interpretation of estimated GFR by clinicians. Data Sources: A systematic search of MEDLINE, without language restriction, between 1999 and 21 October 2011. Study Selection: Cross-sectional studies in adults that compared the performance of 2 or more creatinine-based GFR estimating equations with a reference GFR measurement. Eligible equations were derived or reexpressed and validated by using creatinine measurements traceable to the standard reference material. Data Extraction: Reviewers extracted data on population characteristics, measured GFR, creatinine assay, and equation performance. Data Synthesis: Eligible studies compared the MDRD (Modification of Diet in Renal Disease) Study and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations or modifications thereof. In 12 studies in North America, Europe, and Australia, the CKD-EPI equation performed better at higher GFRs (approximately >60 mL/min per 1.73 m(2)) and the MDRD Study equation performed better at lower GFRs. In 5 of 8 studies in Asia and Africa, the equations were modified to improve their performance by adding a coefficient derived in the local population or removing a coefficient. Limitation: Methods of GFR measurement and study populations were heterogeneous. Conclusion: Neither the CKD-EPI nor the MDRD Study equation is optimal for all populations and GFR ranges. Using a single equation for reporting requires a tradeoff to optimize performance at either higher or lower GFR ranges. A general practice and public health perspective favors the CKD-EPI equation. Primary Funding Source: Kidney Disease: Improving Global Outcomes foundation.

PMID: 22312131 [PubMed - as supplied by publisher]

End-of-Life Care Discussions Among Patients With Advanced Cancer: A Cohort Study.

Ann Intern Med. 2012 Feb 7;156(3):204-10

Authors: Mack JW, Cronin A, Taback N, Huskamp HA, Keating NL, Malin JL, Earle CC, Weeks JC

Abstract
Background: National guidelines recommend that physicians discuss end-of-life (EOL) care planning with patients with cancer whose life expectancy is less than 1 year. Objective: To evaluate the incidence of EOL care discussions for patients with stage IV lung or colorectal cancer and where, when, and with whom these discussions take place. Design: Prospective cohort study of patients diagnosed with lung or colorectal cancer from 2003 to 2005. Setting: Participants lived in Northern California, Los Angeles County, North Carolina, Iowa, or Alabama or received care in 1 of 5 large HMOs or 1 of 15 Veterans Health Administration sites. Patients: 2155 patients with stage IV lung or colorectal cancer. Measurements: End-of-life care discussions reported in patient and surrogate interviews or documented in medical records through 15 months after diagnosis. Results: 73% of patients had EOL care discussions identified by at least 1 source. Among the 1470 patients who died during follow-up, 87% had EOL care discussions, compared with 41% of the 685 patients who were alive at the end of follow-up. Of the 1081 first EOL care discussions documented in records, 55% occurred in the hospital. Oncologists documented EOL care discussions with only 27% of their patients. Among 959 patients with documented EOL care discussions who died during follow-up, discussions took place a median of 33 days before death. Limitations: The depth and quality of EOL care discussions was not evaluated. Much of the information about discussions came from surrogates of patients who died before baseline interviews could be obtained. Conclusion: Although most patients with stage IV lung or colorectal cancer discuss EOL care planning with physicians before death, many discussions occur during acute hospital care, with providers other than oncologists, and late in the course of illness. Primary Funding Source: National Cancer Institute and Department of Veterans Affairs.

PMID: 22312140 [PubMed - in process]

Virtual autopsy as an alternative to traditional medical autopsy in the intensive care unit: a prospective cohort study.

Ann Intern Med. 2012 Jan 17;156(2):123-30

Authors: Wichmann D, Obbelode F, Vogel H, Hoepker WW, Nierhaus A, Braune S, Sauter G, Pueschel K, Kluge S

Abstract
Background: Autopsy is an important educational and quality-control tool in the intensive care unit (ICU), but rates of traditional medical autopsies have declined worldwide. "Virtual" autopsy involving only advanced radiographic techniques might provide an alternative approach to postmortem examinations. Objective: To assess the value of postmortem multidetector computed tomography as an alternative to medical autopsy. Design: Prospective cohort study. (ClinicalTrials.gov registration number: NCT01040520) Setting: 9 ICUs in a single academic medical center. Consent for both medical and virtual autopsies was sought from the families of all consecutive patients who died in the ICU between 1 January and 30 June 2010. Clinical records were reviewed to determine whether unsuspected autopsy findings would have altered care if known (major diagnosis) or would not have altered care (minor diagnosis). Results: Of 285 patients, 47 underwent both virtual and medical autopsy. Of 196 clinical diagnoses made before death, 173 (88%) were identified by virtual autopsy and 183 (93%) by medical autopsy. Fourteen new major and 88 new minor diagnoses were detected by any autopsy method. The main diagnoses missed by virtual autopsy were cardiovascular events (9 of 72) and cancer (12 of 30). In contrast, medical autopsy missed 13 traumatic fractures and 2 pneumothoraces. Among 115 additional patients in whom only virtual autopsy was performed, 11 new major diagnoses were made. Limitation: Virtual autopsy was performed in only 57% of patients (n = 162); among this group, consent for traditional medical autopsy was obtained for only one third. Conclusion: Virtual autopsy may be useful for identifying diagnoses that traditionally have been identified by medical autopsy. This may also hold true, at least in part, for the educational aspect of medical autopsy (confirming antemortem clinical diagnoses). Further studies are required to confirm these preliminary results. Primary Funding Source: University Medical Center Hamburg-Eppendorf, Germany.

PMID: 22250143 [PubMed - in process]

Comparative Effectiveness of Clostridium difficile Treatments: A Systematic Review.

Ann Intern Med. 2011 Dec 20;155(12):839-47

Authors: Drekonja DM, Butler M, Macdonald R, Bliss D, Filice GA, Rector TS, Wilt TJ

Abstract
Background: Clostridium difficile infection is increasing in incidence and severity. The optimal treatment is unknown. Purpose: To determine whether, among adults with C. difficile infection, treatment with certain antibiotics compared with others results in differences in initial cure, recurrence, and harms. Data Sources: MEDLINE, AMED, ClinicalTrials.gov, and Cochrane databases (search dates: inception through August 2011, limited to English-language reports); bibliography review. Study Selection: Randomized, controlled trials of adults with C. difficile infection, independent of outcomes, who were treated with medications available in the United States. Observational studies reporting strain were included. Data Extraction: Study design, inclusion and exclusion criteria, quality and strength of evidence as assessed by 2 reviewers, study definitions, and duration of treatment and follow-up. Outcomes included initial cure, recurrence, and treatment harms. Data Synthesis: 11 trials that included 1463 participants were identified. Three trials compared metronidazole with vancomycin; 8 compared metronidazole or vancomycin with another agent, combined agents, or placebo. Strain was analyzed in 1 trial and 2 cohort studies. No study comparing 2 antimicrobial agents demonstrated a statistically significant difference for initial cure; all comparisons were of low to moderate strength of evidence. Moderate-strength evidence from 1 study demonstrated that recurrence was decreased with fidaxomicin versus vancomycin (15% vs. 25%; difference, -10 percentage points [95% CI, -17 to -3 percentage points]; P = 0.005). Subgroup analysis of a single study comparing metronidazole with vancomycin for patients who have severe C. difficile infection showed no difference by intention-to-treat analysis; this was rated as insufficient-strength evidence. Harms, when reported, did not differ between treatments in any study. Limitations: Definitions of diarrhea, C. difficile infection, initial cure, and relapse varied. Some studies reported insufficient detail to allow assessment of all randomly assigned participants or of harms. Conclusion: No antimicrobial agent is clearly superior for the initial cure of C. difficile infection. Recurrence is less frequent with fidaxomicin than with vancomycin. Primary Funding Source: U.S. Department of Health and Human Services.

PMID: 22184691 [PubMed - in process]

Interventions to reduce 30-day rehospitalization: a systematic review.

Ann Intern Med. 2011 Oct 18;155(8):520-8

Authors: Hansen LO, Young RS, Hinami K, Leung A, Williams MV

Abstract
BACKGROUND: About 1 in 5 Medicare fee-for-service patients discharged from the hospital is rehospitalized within 30 days. Beginning in 2013, hospitals with high risk-standardized readmission rates will be subject to a Medicare reimbursement penalty.
PURPOSE: To describe interventions evaluated in studies aimed at reducing rehospitalization within 30 days of discharge.
DATA SOURCES: MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched for reports published between January 1975 and January 2011.
STUDY SELECTION: English-language randomized, controlled trials; cohort studies; or noncontrolled before-after studies of interventions to reduce rehospitalization that reported rehospitalization rates within 30 days.
DATA EXTRACTION: 2 reviewers independently identified candidate articles from the results of the initial search on the basis of title and abstract. Two 2-physician reviewer teams reviewed the full text of candidate articles to identify interventions and assess study quality.
DATA SYNTHESIS: 43 articles were identified, and a taxonomy was developed to categorize interventions into 3 domains that encompassed 12 distinct activities. Predischarge interventions included patient education, medication reconciliation, discharge planning, and scheduling of a follow-up appointment before discharge. Postdischarge interventions included follow-up telephone calls, patient-activated hotlines, timely communication with ambulatory providers, timely ambulatory provider follow-up, and postdischarge home visits. Bridging interventions included transition coaches, physician continuity across the inpatient and outpatient setting, and patient-centered discharge instruction.
LIMITATIONS: Inadequate description of individual studies' interventions precluded meta-analysis of effects. Many studies identified in the review were single-institution assessments of quality improvement activities rather than those with experimental designs. Several common interventions have not been studied outside of multicomponent "discharge bundles."
CONCLUSION: No single intervention implemented alone was regularly associated with reduced risk for 30-day rehospitalization.
PRIMARY FUNDING SOURCE: None.

PMID: 22007045 [PubMed - indexed for MEDLINE]

A 5-item score predicted risk for warfarin-associated major hemorrhage in patients with atrial fibrillation.

Ann Intern Med. 2011 Nov 15;155(10):JC513

Authors:

PMID: 22084360 [PubMed - in process]

Risks for Stroke, Bleeding, and Death in Patients With Atrial Fibrillation Receiving Dabigatran or Warfarin in Relation to the CHADS2 Score: A Subgroup Analysis of the RE-LY Trial.

Ann Intern Med. 2011 Nov 15;155(10):660-667

Authors: Oldgren J, Alings M, Darius H, Diener HC, Eikelboom J, Ezekowitz MD, Kamensky G, Reilly PA, Yang S, Yusuf S, Wallentin L, Connolly SJ,

Abstract
Background: CHADS(2) is a simple, validated risk score for predicting the risk for stroke in patients with atrial fibrillation not treated with anticoagulants. There are sparse data on the risk for thrombotic and bleeding complications according to the CHADS(2) score in patients receiving anticoagulant therapy. Objective: To evaluate the prognostic importance of CHADS(2) risk score in patients with atrial fibrillation receiving oral anticoagulants, including the vitamin K antagonist warfarin and the direct thrombin inhibitor dabigatran. Design: Subgroup analysis of a randomized, controlled trial. (ClinicalTrials.gov registration number: NCT00262600) Setting: Multinational study setting. Patients: 18 112 patients with atrial fibrillation who were receiving oral anticoagulants. Measurements: Baseline CHADS(2) score, which assigns 1 point each for congestive heart failure, hypertension, age 75 years or older, and diabetes mellitus and 2 points for stroke. Results: Distribution of CHADS(2) scores were as follows: 0 to 1-5775 patients; 2-6455 patients; and 3 to 6-5882 patients. Annual rates of the primary outcome of stroke or systemic embolism among all participants were 0.93% in patients with a CHADS(2) score of 0 to 1, 1.22% in those with a score of 2, and 2.24% in those with a score of 3 to 6. Annual rates of other outcomes among all participants with CHADS(2) scores of 0 to 1, 2, and 3 to 6, respectively, were the following: major bleeding, 2.26%, 3.11%, and 4.42%; intracranial bleeding, 0.31%, 0.40%, and 0.61%; and vascular mortality, 1.35%, 2.39%, and 3.68% (P < 0.001 for all comparisons). Rates of stroke or systemic embolism, major and intracranial bleeding, and vascular and total mortality each increased in the warfarin and dabigatran groups as CHADS(2) score increased. The rates of stroke or systemic embolism with dabigatran, 150 mg twice daily, and of intracranial bleeding with dabigatran, 150 mg or 110 mg twice daily, were lower than those with warfarin; there was no significant heterogeneity in subgroups defined by CHADS(2) scores. Limitation: These analyses were not prespecified and should be deemed exploratory. Conclusion: Higher CHADS(2) scores were associated with increased risks for stroke or systemic embolism, bleeding, and death in patients with atrial fibrillation receiving oral anticoagulants. Primary Funding Source: Boehringer Ingelheim.

PMID: 22084332 [PubMed - as supplied by publisher]

Net Clinical Benefit of Adding Clopidogrel to Aspirin Therapy in Patients With Atrial Fibrillation for Whom Vitamin K Antagonists Are Unsuitable.

Ann Intern Med. 2011 Nov 1;155(9):579-586

Authors: Connolly SJ, Eikelboom JW, Ng J, Hirsh J, Yusuf S, Pogue J, de Caterina R, Hohnloser S, Hart RG,

Abstract
Background: Adding clopidogrel to aspirin therapy reduces stroke in patients with atrial fibrillation (AF) but increases hemorrhage. Objective: To quantify the net benefit of adding clopidogrel to aspirin therapy, accounting for differences in clinical significance between ischemic and hemorrhagic events. Design: Observational cohort study to assign the relative weighting of events and post hoc analysis of randomized trial data to assess net benefit of dual antiplatelet therapy in the ACTIVE (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) clinical trials. Setting: Global randomized clinical trial. Patients: 10 041 patients with AF, 7554 of whom were not candidates for warfarin therapy. Measurements: Ischemic events (ischemic stroke or myocardial infarction) and hemorrhagic events (hemorrhagic stroke or subdural or extracranial bleeding), weighted by the hazard ratio for death (or death or disability) after an event relative to death (or death or disability) after ischemic stroke. The net clinical benefit of dual antiplatelet therapy in the ACTIVE A trial participants was defined as the sum of weighted event incidence with dual antiplatelet therapy subtracted from the sum of weighted event incidence on control treatment, expressed as ischemic stroke equivalents prevented per 100 patients years. Results: Adding clopidogrel to aspirin therapy prevented 0.57 ischemic stroke equivalent (95% CI, -0.12 to 1.24) per 100 patient-years of treatment when weighted by hazard for death after ischemia or hemorrhage and 0.67 ischemic stroke equivalent (CI, -0.03 to 1.18) when weighted by death or disability after ischemia or hemorrhage. Limitation: No attempt was made to relate deaths used for weighting to events; disability data were missing for more than one half of patients. Conclusion: Adding clopidogrel to aspirin therapy resulted in a modest net benefit among patients with AF for whom warfarin was unsuitable. The benefit would probably be clinically relevant for some patients, but estimates could not exclude the possibility of either no benefit or very small harm in this population. Primary Funding Source: Bristol-Myers Squibb and sanofi-aventis.

PMID: 22041946 [PubMed - as supplied by publisher]