Roderick MacDonald

Diagnosis and Management of Stable Chronic Obstructive Pulmonary Disease: A Clinical Practice Guideline Update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society

DESCRIPTION This guideline is an official statement of the American College of Physicians (ACP), American College of Chest Physicians (ACCP), American Thoracic Society (ATS), and European Respiratory Society (ERS). It represents an update of the 2007 ACP clinical practice guideline on diagnosis and management of stable chronic obstructive pulmonary disease (COPD) and is intended for clinicians who manage patients with COPD. This guideline addresses the value of history and physical examination for predicting airflow obstruction; the value of spirometry for screening or diagnosis of COPD; and COPD management strategies, specifically evaluation of various inhaled therapies (anticholinergics, long-acting β-agonists, and corticosteroids), pulmonary rehabilitation programs, and supplemental oxygen therapy. METHODS This guideline is based on a targeted literature update from March 2007 to December 2009 to evaluate the evidence and update the 2007 ACP clinical practice guideline on diagnosis and management of stable COPD. RECOMMENDATION 1: ACP, ACCP, ATS, and ERS recommend that spirometry should be obtained to diagnose airflow obstruction in patients with respiratory symptoms (Grade: strong recommendation, moderate-quality evidence). Spirometry should not be used to screen for airflow obstruction in individuals without respiratory symptoms (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 2: For stable COPD patients with respiratory symptoms and FEV(1) between 60% and 80% predicted, ACP, ACCP, ATS, and ERS suggest that treatment with inhaled bronchodilators may be used (Grade: weak recommendation, low-quality evidence). RECOMMENDATION 3: For stable COPD patients with respiratory symptoms and FEV(1) <60% predicted, ACP, ACCP, ATS, and ERS recommend treatment with inhaled bronchodilators (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 4: ACP, ACCP, ATS, and ERS recommend that clinicians prescribe monotherapy using either long-acting inhaled anticholinergics or long-acting inhaled β-agonists for symptomatic patients with COPD and FEV(1) <60% predicted. (Grade: strong recommendation, moderate-quality evidence). Clinicians should base the choice of specific monotherapy on patient preference, cost, and adverse effect profile. RECOMMENDATION 5: ACP, ACCP, ATS, and ERS suggest that clinicians may administer combination inhaled therapies (long-acting inhaled anticholinergics, long-acting inhaled β-agonists, or inhaled corticosteroids) for symptomatic patients with stable COPD and FEV(1)<60% predicted (Grade: weak recommendation, moderate-quality evidence). RECOMMENDATION 6: ACP, ACCP, ATS, and ERS recommend that clinicians should prescribe pulmonary rehabilitation for symptomatic patients with an FEV(1) <50% predicted (Grade: strong recommendation, moderate-quality evidence). Clinicians may consider pulmonary rehabilitation for symptomatic or exercise-limited patients with an FEV(1) >50% predicted. (Grade: weak recommendation, moderate-quality evidence). RECOMMENDATION 7: ACP, ACCP, ATS, and ERS recommend that clinicians should prescribe continuous oxygen therapy in patients with COPD who have severe resting hypoxemia (Pao(2) ≤55 mm Hg or Spo(2) ≤88%) (Grade: strong recommendation, moderate-quality evidence).

Phytoestrogens for treatment of menopausal symptoms: a systematic review

OBJECTIVE: To assess the efficacy and tolerability of phytoestrogens for treatment of menopausal symptoms. DATA SOURCES: We searched the Cochrane Library and MEDLINE from 1966 to March 2004, using a detailed list of terms related to phytoestrogens and menopausal symptoms and also hand-searched abstracts from relevant meetings. METHODS OF STUDY SELECTION: Randomized trials were eligible if they involved symptomatic perimenopausal or postmenopausal women, compared phytoestrogen with placebo or control, reported hot flush frequency or menopausal symptom scores, and were at least 4 weeks in duration. TABULATION, INTEGRATION, AND RESULTS: Data were extracted onto standardized forms using a prospectively developed protocol. Twenty-five trials involving 2,348 participants met criteria. At baseline, the mean age was 53.1 years, mean duration of menopause was 4.3 years, and mean daily hot flush frequency was 7.1. Mean study duration was 17 weeks. Trials were grouped into categories according to type of phytoestrogen: soy foods, beverages, or powders (n = 11); soy extracts (n = 9); and red clover extracts (n = 5). Of the 8 soy food trials reporting hot flush frequency outcomes, 7 were negative. Five trials of soy foods provided information to calculate effect sizes; these were in the small-to-medium range, favoring placebo in 3 trials and soy in 2. Of the 5 soy extract trials reporting hot flush frequency, 3 (including the 2 largest trials) were negative. Effect sizes were calculated for 2 soy extract trials: one favored placebo with small effect size and the other favored soy with moderate effect size. Red clover trials showed no improvement in hot flush frequency (weighted mean difference −0.60, 95% confidence interval −1.71 to 0.51). Adverse effects were primarily gastrointestinal and taste intolerance in the soy food and beverage trials. CONCLUSION: The available evidence suggests that phytoestrogens available as soy foods, soy extracts, and red clover extracts do not improve hot flushes or other menopausal symptoms.

Teledermatology for diagnosis and management of skin conditions: a systematic review.

OBJECTIVE We performed a systematic review of the literature addressing teledermatology: (1) diagnostic accuracy/concordance; (2) management accuracy/concordance; (3) clinical outcomes; and (4) costs. METHODS Peer-reviewed controlled trials published in English between 1990 and 2009 were identified through MEDLINE and PubMed searches. RESULTS Of 78 included studies, approximately two-thirds comparing teledermatology and clinic dermatology found better diagnostic accuracy with clinic dermatology. Diagnostic concordance of store and forward with clinic dermatology was good; concordance rates for live interactive and clinic dermatology were higher, but based on fewer patients. Overall rates of management accuracy were equivalent, but teledermatology and teledermatoscopy were inferior to clinic dermatology for malignant lesions. Management concordance was fair to excellent. There was insufficient evidence to evaluate clinical course outcomes. Patient satisfaction and preferences were comparable. Teledermatology reduced time to treatment and clinic visits and was cost-effective if certain assumptions were met. LIMITATIONS Heterogeneity in studies (design, skin conditions, outcomes) limited the ability to pool data. CONCLUSION The benefits of teledermatology need to be evaluated in the context of potential limitations.

Meta-analysis: effect of patient self-testing and self-management of long-term anticoagulation on major clinical outcomes.

BACKGROUND Anticoagulation with vitamin K antagonists reduces major thromboembolic complications in at-risk patients. With portable monitoring devices, patients can conduct their own international normalized ratio testing and dose adjustment at home. PURPOSE To determine whether patient self-testing (PST), alone or in combination with self-adjustment of doses (patient self-management [PSM]), is associated with a reduction in thromboembolic complications and all-cause mortality without an increase in major bleeding events compared with usual care. DATA SOURCES MEDLINE and the Cochrane Central Register of Controlled Trials. STUDY SELECTION Studies published in English from 1966 to October 2010 that enrolled outpatient adults receiving long-term (>3 months) oral anticoagulant therapy and that compared PST or PSM with care in a physicians office or an anticoagulation clinic were included. DATA EXTRACTION Two investigators reviewed each article. Three investigators extracted data from articles that met inclusion criteria by using standardized data abstraction forms. Studies were assessed for quality, and the overall strength of evidence was rated for each clinical outcome. DATA SYNTHESIS Twenty-two trials, with a total of 8413 patients, were included. In one half of the trials, fewer than 50% of potentially eligible persons successfully completed the training and agreed to be randomly assigned. Patients randomly assigned to PST or PSM had lower total mortality (Peto odds ratio [OR], 0.74 [95% CI, 0.63 to 0.87]), lower risk for major thromboembolism (Peto OR, 0.58 [CI, 0.45 to 0.75]), and no increased risk for a major bleeding event (Peto OR, 0.89 [CI, 0.75 to 1.05]). The strength of evidence was moderate for the bleeding and thromboembolism outcomes but low for mortality. Eight of 11 trials reported that patient satisfaction, quality of life, or both was better with PST or PSM than with usual care. LIMITATIONS In one half of the trials, fewer than 50% of the potentially eligible patients were randomly assigned. Only 5 trials were considered high quality, and only 2 were conducted in the United States. No studies addressed whether PST or PSM is safe during the high-risk initiation phase. CONCLUSION Compared with usual care, PST with or without PSM is associated with significantly fewer deaths and thromboembolic events, without increased risk for a serious bleeding event, for a highly selected group of motivated adult patients requiring long-term anticoagulation with vitamin K antagonists. Whether this care model is cost-effective and can be implemented successfully in typical U.S. health care settings requires further study. PRIMARY FUNDING SOURCE U.S. Department of Veterans Affairs Health Services Research and Development Service.

Venous thromboembolism prophylaxis in hospitalized medical patients and those with stroke: a background review for an American College of Physicians Clinical Practice Guideline.

BACKGROUND Venous thromboembolism prophylaxis has been recommended for nonsurgical patients, but its effectiveness remains uncertain. PURPOSE To assess the benefits and harms of prophylaxis in hospitalized adult medical patients and those with acute stroke. DATA SOURCES MEDLINE and the Cochrane Library from 1950 through April 2011, reference lists, and study authors. STUDY SELECTION English-language randomized trials were included if they provided clinical outcomes and evaluated therapy with low-dose heparin or related agents or mechanical measures compared with placebo, no treatment, or other active prophylaxis in the target population. DATA EXTRACTION Two independent investigators extracted data on study characteristics and clinical outcomes up to 120 days after randomization. The primary outcome was total mortality. DATA SYNTHESIS In medical patients, heparin prophylaxis did not reduce total mortality but did result in fewer pulmonary embolisms (PEs) (odds ratio [OR], 0.69 [95% CI, 0.52 to 0.90], but with evidence of publication bias) and an increase in all bleeding events (risk ratio [RR], 1.34 [CI, 1.08 to 1.66]). Heparin prophylaxis had no statistically significant effect on any outcome in patients with acute stroke except for an increase in major bleeding events (OR, 1.66 [CI, 1.20 to 2.28]). When trials of medical patients and those with stroke were considered together (18 studies; 36,122 patients), heparin prophylaxis reduced the incidence of PE (OR, 0.70 [CI, 0.56 to 0.87]; absolute reduction, 3 events per 1000 patients treated [CI, 1 to 5 events]) but increased the incidence of all bleeding (RR, 1.28 [CI, 1.05 to 1.56]) and major bleeding events (OR, 1.61 [CI, 1.23 to 2.10]), with an absolute increase of 9 bleeding events per 1000 patients treated (CI, 2 to 18 events), 4 of which were major (CI, 1 to 7 events). A reduction in total mortality approached statistical significance (RR, 0.93 [CI, 0.86 to 1.00]; P = 0.056; absolute decrease, 6 deaths per 1000 patients treated [CI, 0 to 11 deaths]). No statistically significant differences in clinical outcomes were observed in the 14 trials that compared unfractionated heparin with low-molecular-weight heparin. No improvements in clinical outcomes were seen in the 3 studies of mechanical prophylaxis in patients with stroke, but more patients had lower-extremity skin damage (RR, 4.02 [CI, 2.34 to 6.91])-an increase of 39 events per 1000 patients treated (CI, 17 to 77 events). LIMITATION Non-English-language studies were not included, but these were few and small. CONCLUSION Heparin prophylaxis had no significant effect on mortality, may have reduced PE in medical patients and all patients combined, and led to more bleeding and major bleeding events, thus resulting in little or no net benefit. No differences in benefits or harms were found according to type of heparin used. Mechanical prophylaxis provided no benefit and resulted in clinically important harm to patients with stroke. PRIMARY FUNDING SOURCE American College of Physicians.

Systematic Review: Effective Management Strategies for Lactose Intolerance

BACKGROUND Lactose intolerance resulting in gastrointestinal symptoms is a common health concern. Diagnosis and management of this condition remain unclear. PURPOSE To assess the maximum tolerable dose of lactose and interventions for reducing symptoms of lactose intolerance among persons with lactose intolerance and malabsorption. DATA SOURCES Multiple electronic databases, including MEDLINE and the Cochrane Library, for trials published in English from 1967 through November 2009. STUDY SELECTION Randomized, controlled trials of individuals with lactose intolerance or malabsorption. DATA EXTRACTION Three investigators independently reviewed articles, extracted data, and assessed study quality. DATA SYNTHESIS 36 unique randomized studies (26 on lactase- or lactose-hydrolyzed milk supplements, lactose-reduced milk, or tolerable doses of lactose; 7 on probiotics; 2 on incremental lactose administration for colonic adaptation; and 1 on another agent) met inclusion criteria. Moderate-quality evidence indicated that 12 to 15 g of lactose (approximately 1 cup of milk) is well tolerated by most adults. Evidence was insufficient that lactose-reduced solution or milk with a lactose content of 0 to 2 g, compared with greater than 12 g, is effective in reducing symptoms of lactose intolerance. Evidence for probiotics, colonic adaptation, and other agents was also insufficient. LIMITATIONS Most studies evaluated persons with lactose malabsorption rather than lactose intolerance. Variation in enrollment criteria, outcome reporting, and the composition and dosing of studied agents precluded pooling of results and limited interpretation. CONCLUSION Most individuals with presumed lactose intolerance or malabsorption can tolerate 12 to 15 g of lactose. Additional studies are needed to determine the effectiveness of lactose intolerance treatment.

Association between hospital and surgeon radical prostatectomy volume and patient outcomes: a systematic review.

PURPOSE We examined the association between hospital and surgeon volume, and patient outcomes after radical prostatectomy. MATERIALS AND METHODS Databases were searched from 1980 to November 2007 to identify controlled studies published in English. Information on study design, hospital and surgeon annual radical prostatectomy volume, hospital status and patient outcome rates were abstracted using a standardized protocol. Data were pooled with random effects models. RESULTS A total of 17 original investigations reported patient outcomes in categories of hospital and/or surgeon annual number of radical prostatectomies, and met inclusion criteria. Hospitals with volumes above the mean (43 radical prostatectomies per year) had lower surgery related mortality (rate of difference 0.62, 95% CI 0.47-0.81) and morbidity (rate difference -9.7%, 95% CI -15.8, -3.6). Teaching hospitals had an 18% (95% CI -26, -9) lower rate of surgery related complications. Surgeon volume was not significantly associated with surgery related mortality or positive surgical margins. However, the rate of late urinary complications was 2.4% lower (95% CI -5, -0.1) and the rate of long-term incontinence was 1.2% lower (95% CI -2.5, -0.1) for each 10 additional radical prostatectomies performed by the surgeon annually. Length of stay was lower, corresponding to surgeon volume. CONCLUSIONS Higher provider volumes are associated with better outcomes after radical prostatectomy. Greater understanding of factors leading to this volume-outcome relationship, and the potential benefits and harms of increased regionalization is needed.

Medical Management to Prevent Recurrent Nephrolithiasis in Adults: A Systematic Review for an American College of Physicians Clinical Guideline

BACKGROUND Optimum management to prevent recurrent kidney stones is uncertain. PURPOSE To evaluate the benefits and harms of interventions to prevent recurrent kidney stones. DATA SOURCES MEDLINE, Cochrane, and other databases through September 2012 and reference lists of systematic reviews and randomized, controlled trials (RCTs). STUDY SELECTION 28 English-language RCTs that studied treatments to prevent recurrent kidney stones and reported stone outcomes. DATA EXTRACTION One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and graded strength of evidence. DATA SYNTHESIS In patients with 1 past calcium stone, low-strength evidence showed that increased fluid intake halved recurrent composite stone risk compared with no treatment (relative risk [RR], 0.45 [95% CI, 0.24 to 0.84]). Low-strength evidence showed that reducing soft-drink consumption decreased recurrent symptomatic stone risk (RR, 0.83 [CI, 0.71 to 0.98]). In patients with multiple past calcium stones, most of whom were receiving increased fluid intake, moderate-strength evidence showed that thiazides (RR, 0.52 [CI, 0.39 to 0.69]), citrates (RR, 0.25 [CI, 0.14 to 0.44]), and allopurinol (RR, 0.59 [CI, 0.42 to 0.84]) each further reduced composite stone recurrence risk compared with placebo or control, although the benefit from allopurinol seemed limited to patients with baseline hyperuricemia or hyperuricosuria. Other baseline biochemistry measures did not allow prediction of treatment efficacy. Low-strength evidence showed that neither citrate nor allopurinol combined with thiazide was superior to thiazide alone. There were few withdrawals among patients with increased fluid intake, many among those with other dietary interventions and more among those who received thiazide and citrate than among control patients. Reporting of adverse events was poor. LIMITATIONS Most trial participants had idiopathic calcium stones. Nearly all studies reported a composite (including asymptomatic) stone recurrence outcome. CONCLUSION In patients with 1 past calcium stone, increased fluid intake reduced recurrence risk. In patients with multiple past calcium stones, addition of thiazide, citrate, or allopurinol further reduced risk. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.

Screening for, Monitoring, and Treatment of Chronic Kidney Disease Stages 1 to 3: A Systematic Review for the U.S. Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline

This analysis suggests that one-time general consent is better than a gift model for addressing 5 central challenges that arise in the context of obtaining and storing human biological samples for future research. This conclusion supports the suggestion made in a recent Advance Notice of Proposed Rulemaking to incorporate one-time general consent for research with human biological samples into any revisions of the federal regulations.Screening and monitoring for chronic kidney disease (CKD) could lead to earlier interventions that improve clinical outcomes. This review summarizes evidence on the benefits and harms of screening ...

Comparative effectiveness of Clostridium difficile treatments: a systematic review

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.