Chris Del Mar

Bed rest: a potentially harmful treatment needing more careful evaluation

BACKGROUND Bed rest is not only used in the management of patients who are not able to mobilise, but is also prescribed as a treatment for a large number of medical conditions, a procedure that has been challenged. We searched the literature for evidence of benefit or harm of bed rest for any condition. METHODS We systematically searched MEDLINE and the Cochrane library, and retrieved reports on randomised controlled trials of bed rest versus early mobilisation for any medical condition, including medical procedures. FINDINGS 39 trials of bed rest for 15 different conditions (total patients 5777) were found. In 24 trials investigating bed rest following a medical procedure, no outcomes improved significantly and eight worsened significantly in some procedures (lumbar puncture, spinal anaesthesia, radiculography, and cardiac catheterisation). In 15 trials investigating bed rest as a primary treatment, no outcomes improved significantly and nine worsened significantly for some conditions (acute low back pain, labour, proteinuric hypertension during pregnancy, myocardial infarction, and acute infectious hepatitis). INTERPRETATION We should not assume any efficacy for bed rest. Further studies need to be done to establish evidence for the benefit or harm of bed rest as a treatment.

Reducing Inappropriate Polypharmacy: The Process of Deprescribing

Inappropriate polypharmacy, especially in older people, imposes a substantial burden of adverse drug events, ill health, disability, hospitalization, and even death. The single most important predictor of inappropriate prescribing and risk of adverse drug events in older patients is the number of prescribed drugs. Deprescribing is the process of tapering or stopping drugs, aimed at minimizing polypharmacy and improving patient outcomes. Evidence of efficacy for deprescribing is emerging from randomized trials and observational studies. A deprescribing protocol is proposed comprising 5 steps: (1) ascertain all drugs the patient is currently taking and the reasons for each one; (2) consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention; (3) assess each drug in regard to its current or future benefit potential compared with current or future harm or burden potential; (4) prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes; and (5) implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects. Whereas patient and prescriber barriers to deprescribing exist, resources and strategies are available that facilitate deliberate yet judicious deprescribing and deserve wider application.

Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis

Objectives To update a 2005 Cochrane review that assessed the effects of neuraminidase inhibitors in preventing or ameliorating the symptoms of influenza, the transmission of influenza, and complications from influenza in healthy adults, and to estimate the frequency of adverse effects. Search strategy An updated search of the Cochrane central register of controlled trials (Cochrane Library 2009, issue 2), which contains the Acute Respiratory Infections Group’s specialised register, Medline (1950-Aug 2009), Embase (1980-Aug 2009), and post-marketing pharmacovigilance data and comparative safety cohorts. Selection criteria Randomised placebo controlled studies of neuraminidase inhibitors in otherwise healthy adults exposed to naturally occurring influenza. Main outcome measures Duration and incidence of symptoms; incidence of lower respiratory tract infections, or their proxies; and adverse events. Data extraction Two reviewers applied inclusion criteria, assessed trial quality, and extracted data. Data analysis Comparisons were structured into prophylaxis, treatment, and adverse events, with further subdivision by outcome and dose. Results 20 trials were included: four on prophylaxis, 12 on treatment, and four on postexposure prophylaxis. For prophylaxis, neuraminidase inhibitors had no effect against influenza-like illness or asymptomatic influenza. The efficacy of oral oseltamivir against symptomatic laboratory confirmed influenza was 61% (risk ratio 0.39, 95% confidence interval 0.18 to 0.85) at 75 mg daily and 73% (0.27, 0.11 to 0.67) at 150 mg daily. Inhaled zanamivir 10 mg daily was 62% efficacious (0.38, 0.17 to 0.85). Oseltamivir for postexposure prophylaxis had an efficacy of 58% (95% confidence interval 15% to 79%) and 84% (49% to 95%) in two trials of households. Zanamivir performed similarly. The hazard ratios for time to alleviation of influenza-like illness symptoms were in favour of treatment: 1.20 (95% confidence interval 1.06 to 1.35) for oseltamivir and 1.24 (1.13 to 1.36) for zanamivir. Eight unpublished studies on complications were ineligible and therefore excluded. The remaining evidence suggests oseltamivir did not reduce influenza related lower respiratory tract complications (risk ratio 0.55, 95% confidence interval 0.22 to 1.35). From trial evidence, oseltamivir induced nausea (odds ratio 1.79, 95% confidence interval 1.10 to 2.93). Evidence of rarer adverse events from pharmacovigilance was of poor quality or possibly under-reported. Conclusion Neuraminidase inhibitors have modest effectiveness against the symptoms of influenza in otherwise healthy adults. The drugs are effective postexposure against laboratory confirmed influenza, but this is a small component of influenza-like illness, so for this outcome neuraminidase inhibitors are not effective. Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal influenza. Paucity of good data has undermined previous findings for oseltamivir’s prevention of complications from influenza. Independent randomised trials to resolve these uncertainties are needed.

Physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review

Objective To review systematically the evidence of effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. Data sources Cochrane Library, Medline, OldMedline, Embase, and CINAHL, without restrictions on language or publication. Data selection Studies of any intervention to prevent the transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection, and hygiene). A search of study designs included randomised trials, cohort, case-control, crossover, before and after, and time series studies. After scanning of the titles, abstracts and full text articles as a first filter, a standardised form was used to assess the eligibility of the remainder. Risk of bias of randomised studies was assessed for generation of the allocation sequence, allocation concealment, blinding, and follow-up. Non-randomised studies were assessed for the presence of potential confounders and classified as being at low, medium, or high risk of bias. Data synthesis 58 papers of 59 studies were included. The quality of the studies was poor for all four randomised controlled trials and most cluster randomised controlled trials; the observational studies were of mixed quality. Meta-analysis of six case-control studies suggested that physical measures are highly effective in preventing the spread of severe acute respiratory syndrome: handwashing more than 10 times daily (odds ratio 0.45, 95% confidence interval 0.36 to 0.57; number needed to treat=4, 95% confidence interval 3.65 to 5.52), wearing masks (0.32, 0.25 to 0.40; NNT=6, 4.54 to 8.03), wearing N95 masks (0.09, 0.03 to 0.30; NNT=3, 2.37 to 4.06), wearing gloves (0.43, 0.29 to 0.65; NNT=5, 4.15 to 15.41), wearing gowns (0.23, 0.14 to 0.37; NNT=5, 3.37 to 7.12), and handwashing, masks, gloves, and gowns combined (0.09, 0.02 to 0.35; NNT=3, 2.66 to 4.97). The combination was also effective in interrupting the spread of influenza within households. The highest quality cluster randomised trials suggested that spread of respiratory viruses can be prevented by hygienic measures in younger children and within households. Evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks was limited, but they caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to reduce respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. Evidence was limited for social distancing being effective, especially if related to risk of exposure—that is, the higher the risk the longer the distancing period. Conclusion Routine long term implementation of some of the measures to interrupt or reduce the spread of respiratory viruses might be difficult. However, many simple and low cost interventions reduce the transmission of epidemic respiratory viruses. More resources should be invested into studying which physical interventions are the most effective, flexible, and cost effective means of minimising the impact of acute respiratory tract infections.

WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus

Summary Recent spread of avian influenza A (H5N1) virus to poultry and wild birds has increased the threat of human infections with H5N1 virus worldwide. Despite international agreement to stockpile antivirals, evidence-based guidelines for their use do not exist. WHO assembled an international multidisciplinary panel to develop rapid advice for the pharmacological management of human H5N1 virus infection in the current pandemic alert period. A transparent methodological guideline process on the basis of the Grading Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to develop evidence-based guidelines. Our development of specific recommendations for treatment and chemoprophylaxis of sporadic H5N1 infection resulted from the benefits, harms, burden, and cost of interventions in several patient and exposure groups. Overall, the quality of the underlying evidence for all recommendations was rated as very low because it was based on small case series of H5N1 patients, on extrapolation from preclinical studies, and high quality studies of seasonal influenza. A strong recommendation to treat H5N1 patients with oseltamivir was made in part because of the severity of the disease. Similarly, strong recommendations were made to use neuraminidase inhibitors as chemoprophylaxis in high-risk exposure populations. Emergence of other novel influenza A viral subtypes with pandemic potential, or changes in the pathogenicity of H5N1 virus strains, will require an update of these guidelines and WHO will be monitoring this closely.

The Connection Between Evidence-Based Medicine and Shared Decision Making

Evidence-based medicine (EBM) and shared decision making (SDM) are both essential to quality health care, yet the interdependence between these 2 approaches is not generally appreciated. Evidence-based medicine should begin and end with the patient: after finding and appraising the evidence and integrating its inferences with their expertise, clinicians attempt a decision that reflects their patient’s values and circumstances. Incorporating patient values, preferences, and circumstances is probably the most difficult and poorly mapped step—yet it receives the least attention.1 This has led to a common criticism that EBM ignores patients’ values and preferences—explicitly not its intention.2 Shared decision making is the process of clinician and patient jointly participating in a health decision after discussing the options, the benefits and harms, and considering the patient’s values, preferences, and circumstances. It is the intersection of patient-centered communication skills and EBM, in the pinnacle of good patient care (Figure).

The Imperative to Share Clinical Study Reports: Recommendations from the Tamiflu Experience

Peter Doshi and colleagues describe their experience trying and failing to access clinical study reports from the manufacturer of Tamiflu and challenge industry to defend their current position of RCT data secrecy.

Telephone counseling for physical activity and diet in primary care patients.

BACKGROUND The delivery of effective interventions to assist patients to improve their physical activity and dietary behaviors is a challenge in the busy primary care setting. DESIGN Cluster RCT with practices randomized to telephone counseling intervention or usual care. Data collection took place from February 2005 to November 2007, with analysis from December 2007 to April 2008. SETTING/PARTICIPANTS Four-hundred thirty-four adult patients with type 2 diabetes or hypertension (mean age=58.2 [SD=11.8]; 61% female; mean BMI=31.1 [SD=6.8]) from a disadvantaged community were recruited from ten primary care practices. INTERVENTION Twelve-month telephone counseling intervention. MAIN OUTCOME MEASURES Physical activity and dietary intake were assessed by self-report at baseline, 4, and 12 months. RESULTS At 12 months, patients in both groups increased moderate-to-vigorous physical activity by a mean of 78 minutes per week (SE=10). Significant intervention effects (telephone counseling minus usual care) were observed for: calories from total fat (decrease of 1.17%; p<0.007), energy from saturated fat (decrease of 0.97%; p<0.007), vegetable intake (increase of 0.71 servings; p<0.039), fruit intake (increase of 0.30 servings; p<0.001), and grams of fiber (increase of 2.23 g; p<0.001). CONCLUSIONS The study targeted a challenging primary care patient sample and, using a telephone-delivered intervention, demonstrated modest improvements in diet and in physical activity. Results suggest that telephone counseling is a feasible means of delivering lifestyle intervention to primary care patients with chronic conditions-patients whose need for ongoing support for lifestyle change is often beyond the capacity of primary healthcare practitioners.

Three questions that patients can ask to improve the quality of information physicians give about treatment options: A cross-over trial

OBJECTIVE To test the effect of three questions (what are my options? what are the benefits and harms? and how likely are these?), on information provided by physicians about treatment options. METHODS We used a cross-over trial using two unannounced standardized patients (SPs) simulating a presentation of mild-moderate depression. One SP was assigned the intervention role (asking the questions), the other the control role. An intervention and control SP visited each physician, order allocated randomly. The study was conducted in family practices in Sydney, Australia, during 2008-09. Data were obtained from consultation audio-recordings. Information about treatment options and patient involvement were analyzed using the Assessing Communication about Evidence and Patient Preferences (ACEPP) tool and the OPTION tool. RESULTS Thirty-six SP visits were completed (18 intervention, 18 control). Scores were higher in intervention consultations than controls: ACEPP scores 21.4 vs. 16.6, p<0.001, difference 4.7 (95% CI 2.3-7.0) and OPTION scores 36 vs. 25, p=0.001, difference 11.5 (95% CI 5.1-17.8), indicating greater information provision and behavior supporting patient involvement. CONCLUSION Asking these three questions improved information given by family physicians and increased physician facilitation of patient involvement. Practice implications. These questions can drive evidence-based practice, strengthen patient-physician communication, and improve safety and quality.

The state of primary-care research.

But for The Lancet to characterise primary-care research as a “lost cause” is unhelpful. This notion implies either that the field is so weak that it cannot be resuscitated or that it is irrelevant anyway. Both are wrong.