Monthly Archives: April 2014

Antibiotics for acute bronchitis?

Smith SM, Fahey T, Smucny J, et al. Antibiotics for acute bronchitis. Cochrane Database

BACKGROUND: The benefits and risks of antibiotics for acute bronchitis remain unclear despite it being one of the most common illnesses seen in primary care.

OBJECTIVES: To assess the effects of antibiotics in improving outcomes and assess adverse effects of antibiotic therapy for patients with a clinical diagnosis of acute bronchitis.

SEARCH METHODS: We searched CENTRAL 2013, Issue 12, MEDLINE (1966 to January week 1, 2014), EMBASE (1974 to January 2014) and LILACS (1982 to January 2014).

SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing any antibiotic therapy with placebo or no treatment in acute bronchitis or acute productive cough, in patients without underlying pulmonary disease.

DATA COLLECTION AND ANALYSIS: At least two review authors extracted data and assessed trial quality.

MAIN RESULTS: Seventeen trials with 3936 participants were included in the primary analysis. The quality of trials was generally good. There was limited evidence to support the use of antibiotics in acute bronchitis. At follow-up, there was no difference in participants described as being clinically improved between antibiotic and placebo groups (11 studies with 3841 participants, risk ratio (RR) 1.07, 95% confidence interval (CI) 0.99 to 1.15; number needed to treat for an additional beneficial outcome (NNTB) 22. Participants given antibiotics were less likely to have a cough (four studies with 275 participants, RR 0.64, 95% CI 0.49 to 0.85; NNTB 6); have a night cough (four studies with 538 participants, RR 0.67, 95% CI 0.54 to 0.83; NNTB 7) and a shorter mean cough duration (seven studies with 2776 participants, mean difference (MD) -0.46 days, 95% CI -0.87 to -0.04). The differences in presence of a productive cough at follow-up and MD of productive cough did not reach statistical significance.Antibiotic-treated patients were more likely to be unimproved according to clinician`s global assessment (six studies with 891 participants, RR 0.61, 95% CI 0.48 to 0.79; NNTB 25); have an abnormal lung exam (five studies with 613 participants, RR 0.54, 95% CI 0.41 to 0.70; NNTB 6); have a reduction in days feeling ill (five studies with 809 participants, MD -0.64 days, 95% CI -1.16 to -0.13) and a reduction in days with limited activity (six studies with 767 participants MD -0.49 days, 95% CI -0.94 to -0.04). The differences in proportions with activity limitations at follow-up did not reach statistical significance. There was a significant trend towards an increase in adverse effects in the antibiotic group (12 studies with 3496 participants) (RR 1.20, 95% CI 1.05 to 1.36; NNT for an additional adverse effect 5).

AUTHORS’ CONCLUSIONS: There is limited evidence to support the use of antibiotics in acute bronchitis. Antibiotics may have a modest beneficial effect in some patients such as frail, elderly people with multimorbidity who may not have been included in trials to date. However, the magnitude of this benefit needs to be considered in the broader context of potential side effects, medicalisation for a self-limiting condition, increased resistance to respiratory pathogens and cost of antibiotic treatment.Syst Rev. 2014 Mar 1;3:CD000245. (Review) PMID: 24585130

Vitamin D has no real effect on bone mineral density

Clinical Question: Does supplemental vitamin D increase bone mineral density?

Bottom LineNot only does supplemental vitamin D not prevent fractures, it also does not have any meaningful effect on bone mineral density (BMD). (LOE = 1a-)

Reference:  Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet 2014;383(9912):146-155.

Study Design: Meta-analysis (randomized controlled trials)

Funding: Government     Allocation: Unknown

Synopsis

 

The authors searched 3 databases for randomized trials that evaluated the effects of vitamin D on BMD. They point out that no meta-analysis has found vitamin D to prevent the (more important) outcome of fractures, and that BMD correlates poorly with fractures. So, they decided to study vitamin D’s effect on the irrelevant outcome of BMD and Lancet chose to publish it. Go figure. Anyway, the authors did a pretty good job on the methods: independent assessment of study eligibility, data extraction, and quality assessment. When discrepancies arose, the authors resolved them through discussion. They also assessed the potential for publication bias graphically and statistically. Ultimately, they included 23 studies with nearly 4100 patients. The studies lasted an average of 2 years. The daily vitamin D doses generally ranged from 100 international units (IU) to 2000 IU. A couple of studies evaluated 20,000 IU to 50,000 IU weekly and 2 studies evaluated 300,000 IU per year. As one might imagine, the studies also evaluated several different sites: femur, hip, trochanter, lumbar spine, forearm. Six of the studies reported that vitamin D increased BMD, 2 reported the vitamin decreased BMD, and the remainder found no overall benefit. The authors pooled the data and reported a small increase in femoral neck BMD, but no increase for any other site. The authors identified publication bias in favor of studies reporting positive results for femoral neck and hip BMD. This bias casts suspicion on the sole finding in this meta-analysis.

 

Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI

IPC safer and as effective as medical prophylaxis; much better than TEDS

Clinical Question

How effective is intermittent pneumatic compression for the prevention of venous thromboembolism in hospitalized patients?

Bottom Line

Intermittent pneumatic compression (IPC) is more effective than doing nothing or using thromboembolic deterrent stockings (TEDS), and is similarly effective to medical thromboprophylaxis for the prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE). It is also safer than anticoagulants. The authors pool the studies to determine absolute risk reductions and numbers needed to treat but this is inappropriate when the baseline risk of DVT, PE, and bleeding varies so much between studies. Using a more statistically correct approach of applying the relative risk from the meta-analysis to the baseline risk of events, I found a number needed to treat to prevent one bleed of 40 for IPC compared with medical thromboprophylaxis, and a number needed to treat of 22 to prevent one DVT by using IPC instead of TEDS. (LOE = 1a)

Reference

Ho KM, Tan JA. Stratified meta-analysis of intermittent pneumatic compression of the lower limbs to prevent venous thromboembolism in hospitalized patients. Circulation 2013;128(9):1003-1020.

Synopsis

The authors performed a careful search for randomized trials comparing IPC with either no treatment, TEDS, or pharmacotherapy in hospitalized patients to prevent DVT or PE. They also looked for studies comparing IPC plus pharmacotherapy with IPC alone. The search included PubMed, Embase (a European database), and the Cochrane Controlled Trials Register. Overall, the authors found 70 trials with a total of 16,164 patients, mostly in surgical and postoperative populations. Most trials included patients undergoing orthopedic surgery, major abdominal surgery, urologic surgery, or neurosurgery. The overall quality of studies was fair, with approximately half failing to adequately report allocation concealment or blindly assess outcomes. IPC was more effective than doing nothing in preventing PE (relative risk [RR] = 0.48; 95% CI, 0.33 – 0.69) and DVT (RR = 0.43; 0.36 – 52). IPC was also more effective than TEDS at preventing DVT (95% CI = 0.61; 0.39 – 0.93) but not PE (RR = 0.64; 0.21 – 1.95). Not surprisingly, when compared with medical thromboprophylaxis (usually with unfractionated or low-molecular-weight heparin), patients randomized to receive IPC had less systemic bleeding or bleeding complications (RR = 0.41; 0.25 – 0.65). The overall likelihood of DVT and PE was similar between patients given IPC or medical thromboprophylaxis,but there was considerable heterogeneity of results for the studies of DVT. There was no significant difference in mortality when medical thromboprophylaxis was added to IPC or when medical thromboprophylaxis was compared with IPC. Finally, adding medical thromboprophylaxis to IPC further reduced the risk of DVT but did not significantly reduce the likelihood of PE. As for TEDS, the relative risk was similar for prevention of DVT and PE, but because PE is much less common, the sample size may have been insufficient to demonstrate a significant reduction even if one actually existed.

Mark H. Ebell, MD, MS
Associate Professor
University of Georgia
Athens, GA

Patients with AF taking aspirin with anticoagulant at increased bleeding risk without clear benefit

Question

In patients with atrial fibrillation, does use of aspirin in addition to an anticoagulant improve or worsen clinical outcomes?

Bottom Line

Many patients with atrial fibrillation (AF) are receiving aspirin (A) in addition to an oral anticoagulant (OAC), despite the fact that 40% of the patients in this study had no indication for aspirin (eg, no known atherosclerotic disease). Concomitant use of aspirin increased the risk of bleeding over OAC alone (adjusted hazard ratio [aHR] = 1.5) without any clear benefit regarding cardiovascular events. This practice persists despite lack of support from randomized trials (the lone potential exception is the group of patients with a mechanical heart valve). This is a case in which less may be more, and randomized trials comparing OAC with A+OAC are needed in this population. (LOE = 2b)

Reference

Steinberg BA, Kim S, Piccini JP, et al, for the ORBIT-AF Investigators and Patients. Use and associated risks of concomitant aspirin therapy with oral anticoagulation in patients with atrial fibrillation: insights from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Registry. Circulation 2013;128(7):721-728.

Synopsis

Most patients with AF are treated with an anticoagulant. Those who also have an indication for an antithrombotic, such as known coronary artery or cerebrovascular disease, may also be given aspirin. The benefit of this incremental therapy (aspirin plus oral anticoagulant [A+OAC]) is uncertain.The authors used a registry of 10,126 adult outpatients being treated for AF; those with reversible cause or short life expectancy were excluded. After also excluding those who were not taking an anticoagulant and those taking other antithrombotics, they were left with 4804 patients who were taking OAC and 2543 who were taking A+OAC. Those using combination therapy were more likely to be male (53% OAC, 66% A+OAC) and more likely to smoke, have hyperlipidemia, diabetes mellitus, or heart failure. A multivariate analysis found that those being given A+OAC had a higher likelihood of known coronary artery disease (adjusted odds ratio [aOR] = 2.2), previous ablation (aOR = 1.6), previous stent placement (aOR 1.5), or previous stroke or transient ischemic attack (aOR = 1.5). Older patients, those with long-standing or persistent AF, those living in the southern or western states, patients with liver or renal disease, and those being cared for by a primary care physician were less likely to be using combination therapy. Using an adjusted propensity score analysis, the authors also looked at the likelihood of adverse outcomes at 6 months between groups. Major bleeding (aHR = 1.5; 95% CI 1.2 – 2.0) and bleeding resulting in hospitalization [aHR = 1.5; 1.2 – 2.0) were both significantly more likely in patients receiving concomitant aspirin therapy. When limiting the analysis to only those patients with previous myocardial infarction (n = 947) or stroke (n = 1042), although the overall number of cardiovascular or bleeding events was small, there was no apparent difference in the likelihood of these events between groups.

Mark H. Ebell, MD, MS
Associate Professor
University of Georgia
Athens, GA