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The Centre for Evidence-Based Medicine (CEBM) at Oxford University develops, promotes and disseminates better evidence for health care.
Association between living with children and outcomes from covid-19: OpenSAFELY cohort study of 12 million adults in England
Objective To investigate whether risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and outcomes of coronavirus disease 2019 (covid-19) differed between adults living with and without children during the first two waves of the UK pandemic. Design Population based cohort study, on behalf of NHS England. Setting Primary care data and pseudonymously linked hospital and intensive care admissions and death records from England, during wave 1 (1 February to 31 August 2020) and wave 2 (1 September to 18 December 2020). Participants Two cohorts of adults (18 years and over) registered at a general practice on 1 February 2020 and 1 September 2020. Main outcome measures Adjusted hazard ratios for SARS-CoV-2 infection, covid-19 related admission to hospital or intensive care, or death from covid-19, by presence of children in the household. Results Among 9 334 392adults aged 65 years and under, during wave 1, living with children was not associated with materially increased risks of recorded SARS-CoV-2 infection, covid-19 related hospital or intensive care admission, or death from covid-19. In wave 2, among adults aged 65 years and under, living with children of any age was associated with an increased risk of recorded SARS-CoV-2 infection (hazard ratio 1.06 (95% confidence interval 1.05 to 1.08) for living with children aged 0-11 years; 1.22 (1.20 to 1.24) for living with children aged 12-18 years) and covid-19 related hospital admission (1.18 (1.06 to 1.31) for living with children aged 0-11; 1.26 (1.12 to 1.40) for living with children aged 12-18). Living with children aged 0-11 was associated with reduced risk of death from both covid-19 and non-covid-19 causes in both waves; living with children of any age was also associated with lower risk of dying from non-covid-19 causes. For adults 65 years and under during wave 2, living with children aged 0-11 years was associated with an increased absolute risk of having SARS-CoV-2 infection recorded of 40-60 per 10 000 people, from 810 to between 850 and 870, and an increase in the number of hospital admissions of 1-5 per 10 000 people, from 160 to between 161 and 165. Living with children aged 12-18 years was associated with an increase of 160-190 per 10 000 in the number of SARS-CoV-2 infections and an increase of 2-6 per 10 000 in the number of hospital admissions. Conclusions In contrast to wave 1, evidence existed of increased risk of reported SARS-CoV-2 infection and covid-19 outcomes among adults living with children during wave 2. However, this did not translate into a materially increased risk of covid-19 mortality, and absolute increases in risk were small.
© AbstractObjective To establish the effect of statins on muscle symptoms in people who had previously reported muscle symptoms when taking statins. Design Series of randomised, placebo controlled n-of-1 trials. Setting Primary care across 50 sites in the United Kingdom, December 2016 to April 2018. Participants 200 participants who had recently stopped or were considering stopping treatment with statins because of muscle symptoms. Interventions Participants were randomised to a sequence of six double blinded treatment periods (two months each) of atorvastatin 20 mg daily or placebo. Main outcome measures At the end of each treatment period, participants rated their muscle symptoms on a visual analogue scale (0-10). The primary analysis compared symptom scores in the statin and placebo periods. Results 151 participants provided symptoms scores for at least one statin period and one placebo period and were included in the primary analysis. Overall, no difference in muscle symptom scores was found between the statin and placebo periods (mean difference statin minus placebo -0.11, 95% confidence interval -0.36 to 0.14; P=0.40)). Withdrawals because of intolerable muscle symptoms were 18 participants (9%) during a statin period and 13 (7%) during a placebo period. Two thirds of those completing the trial reported restarting long term treatment with statins. Conclusions No overall effect of atorvastatin 20 mg on muscle symptoms compared with placebo was found in participants who had previously reported severe muscle symptoms when taking statins. Most people completing the trial intended to restart treatment with statins. N-of-1 trials can assess drug effects at the group level and guide individual treatment. Trial registration ISRCTN30952488, EUDRACT 2016-000141-31, NCT02781064.
BACKGROUND: Uncertainty persists about whether or not statins cause symptomatic muscle adverse effects (e.g. pain, stiffness and weakness) in the absence of severe myositis. OBJECTIVES: To establish the effect of statins on all muscle symptoms, and the effect of statins on muscle symptoms that are perceived to be statin related. DESIGN: A series of 200 double-blinded N-of-1 trials. SETTING: Participants were recruited from 50 general practices in England and Wales. PARTICIPANTS: Patients who were considering discontinuing statin use and those who had discontinued statin use in the last 3 years because of perceived muscle symptoms. INTERVENTIONS: Participants were randomised to a sequence of six 2-month treatment periods during which they received 20 mg of atorvastatin daily or a matched placebo. MAIN OUTCOME MEASURES: The primary outcome was self-reported muscle symptoms rated using a visual analogue scale on the last week of each treatment period. Secondary outcomes included the participant's belief about the cause of their muscle symptoms, the site of muscle symptoms, how the muscle symptoms affected the participant, any other symptoms they experienced, adherence to medication, the participant's decision about statin treatment following the trial, and whether or not they found their own trial result helpful. RESULTS: A total of 151 out of 200 (75.5%) randomised participants provided one or more visual analogue scale measurements in a placebo period and one or more measurements in a statin period, and were included in the primary analysis. There was no evidence of a difference in muscle symptom scores between statin and placebo periods (mean difference statin minus placebo -0.11, 95% confidence interval -0.36 to 0.14; p = 0.398). Withdrawals, adherence and missing data were similar during the statin periods and the placebo periods. CONCLUSIONS: Among people who previously reported severe muscle symptoms while taking statins, this series of randomised N-of-1 trials found no overall effect of statins on muscle symptoms compared with the placebo. The slight difference in withdrawals due to muscle symptoms suggests that statins may contribute to symptoms in a small number of patients. The results are generalisable to patients who are considering discontinuing or have already discontinued statins because of muscle symptoms, and who are willing to re-challenge or participate in their own N-of-1 trial. FUTURE WORK: We recommend that additional statins and doses are explored using N-of-1 trials. More broadly, N-of-1 trials present a useful tool for exploring transient symptoms with other medications. LIMITATIONS: This study used 20-mg doses of atorvastatin only. Furthermore, a dropout rate of 43% was observed, but this was accounted for in the power calculations. TRIAL REGISTRATION: Current Controlled Trials ISRCTN30952488 and EudraCT 2016-000141-31. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 16. See the NIHR Journals Library website for further project information.
Azithromycin for community treatment of suspected COVID-19 in people at increased risk of an adverse clinical course in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial
© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license Background: Azithromycin, an antibiotic with potential antiviral and anti-inflammatory properties, has been used to treat COVID-19, but evidence from community randomised trials is lacking. We aimed to assess the effectiveness of azithromycin to treat suspected COVID-19 among people in the community who had an increased risk of complications. Methods: In this UK-based, primary care, open-label, multi-arm, adaptive platform randomised trial of interventions against COVID-19 in people at increased risk of an adverse clinical course (PRINCIPLE), we randomly assigned people aged 65 years and older, or 50 years and older with at least one comorbidity, who had been unwell for 14 days or less with suspected COVID-19, to usual care plus azithromycin 500 mg daily for three days, usual care plus other interventions, or usual care alone. The trial had two coprimary endpoints measured within 28 days from randomisation: time to first self-reported recovery, analysed using a Bayesian piecewise exponential, and hospital admission or death related to COVID-19, analysed using a Bayesian logistic regression model. Eligible participants with outcome data were included in the primary analysis, and those who received the allocated treatment were included in the safety analysis. The trial is registered with ISRCTN, ISRCTN86534580. Findings: The first participant was recruited to PRINCIPLE on April 2, 2020. The azithromycin group enrolled participants between May 22 and Nov 30, 2020, by which time 2265 participants had been randomly assigned, 540 to azithromycin plus usual care, 875 to usual care alone, and 850 to other interventions. 2120 (94%) of 2265 participants provided follow-up data and were included in the Bayesian primary analysis, 500 participants in the azithromycin plus usual care group, 823 in the usual care alone group, and 797 in other intervention groups. 402 (80%) of 500 participants in the azithromycin plus usual care group and 631 (77%) of 823 participants in the usual care alone group reported feeling recovered within 28 days. We found little evidence of a meaningful benefit in the azithromycin plus usual care group in time to first reported recovery versus usual care alone (hazard ratio 1·08, 95% Bayesian credibility interval [BCI] 0·95 to 1·23), equating to an estimated benefit in median time to first recovery of 0·94 days (95% BCI −0·56 to 2·43). The probability that there was a clinically meaningful benefit of at least 1·5 days in time to recovery was 0·23. 16 (3%) of 500 participants in the azithromycin plus usual care group and 28 (3%) of 823 participants in the usual care alone group were hospitalised (absolute benefit in percentage 0·3%, 95% BCI −1·7 to 2·2). There were no deaths in either study group. Safety outcomes were similar in both groups. Two (1%) of 455 participants in the azothromycin plus usual care group and four (1%) of 668 participants in the usual care alone group reported admission to hospital during the trial, not related to COVID-19. Interpretation: Our findings do not justify the routine use of azithromycin for reducing time to recovery or risk of hospitalisation for people with suspected COVID-19 in the community. These findings have important antibiotic stewardship implications during this pandemic, as inappropriate use of antibiotics leads to increased antimicrobial resistance, and there is evidence that azithromycin use increased during the pandemic in the UK. Funding: UK Research and Innovation and UK Department of Health and Social Care.
Objectives To understand how and why workplace mindfulness-based programmes (MBPs) work or do not work. Design A realist review. Eligibility criteria for selection We considered any studies (experimental quasi-experimental, observational, qualitative and mixed-methods studies) of workplace MBPs as long as they provided data to explain our programme theories. All MBP formats and delivery modes were included. Analysis Consistent with realist review methodology, we systematically screened and analysed data to explain how and why workplace MBPs work or do not work. These explanations were consolidated into a programme theory augmented by theories from organisational literature, such as conservation of resources theory. Results Findings from 75 primary studies suggest that workplace MBPs enable participants (including healthcare professionals) to deal more skillfully with stressful events and improve their well-being. The mechanisms involved can be grouped around awareness/self-regulation, acceptance/compassion, feeling permitted to take care of self, sense of growth and promise of goal attainment. In order for professionals to invest in an MBP and benefit from it, it is important that they feel safe to engage with self-care at work and share emotional difficulties among peers. It is also important that employees are able to link the programme and its activities to existing goals and practices. Concerns of being non-productive, of not getting work done or of being exposed in front of colleagues can result in strategic use of brief mindfulness exercises, non-adherence or drop-out. Conclusions Simply offering an MBP to (healthcare) professionals in order to reduce stress and enhance well-being does not suffice. A supportive environment must exist in order for the programme's benefits to be reaped. PROSPERO registration number CRD42018086280.
Measuring the success of blinding in placebo-controlled trials: Should we be so quick to dismiss it?
‘Blinding’ involves concealing knowledge of which trial participants received the interventions from participants themselves and other trial personnel throughout the trial. Blinding reduces bias arising from the beliefs and expectations of these groups. It is agreed that where possible, blinding should be attempted, for example by ensuring that experimental and control treatments look the same. However, there is a debate about if we should measure whether blinding has been successful, this manuscript will discuss this controversy, including the benefits and risks of measuring blinding within the randomised controlled trial.
Inhaled budesonide for COVID-19 in people at higher risk of adverse outcomes in the community: interim analyses from the PRINCIPLE trial
<jats:p>BACKGROUND Inhaled budesonide has shown efficacy for treating COVID-19 in the community but has not yet been tested in effectiveness trials. METHODS We performed a multicenter, open-label, multi-arm, adaptive platform randomized controlled trial involving people aged ≥65 years, or ≥50 years with comorbidities, and unwell ≤14 days with suspected COVID-19 in the community (PRINCIPLE). Participants were randomized to usual care, usual care plus inhaled budesonide (800μg twice daily for 14 days), or usual care plus other interventions. The co-primary endpoints are time to first self-reported recovery, and hospitalization/death related to COVID-19, both measured over 28 days from randomisation and analysed using Bayesian models. RESULTS The trial opened on April 2, 2020. Randomization to inhaled budesonide began on November 27, 2020 and was stopped on March 31, 2021 based on an interim analysis using data from March 4, 2021. Here, we report updated interim analysis data from March 25, 2021, at which point the trial had randomized 4663 participants with suspected COVID-19. Of these, 2617 (56.1%) tested SARS-CoV-2 positive and contributed data to this interim budesonide primary analysis; 751 budesonide, 1028 usual care and 643 to other interventions. Time to first self-reported recovery was shorter in the budesonide group compared to usual care (hazard ratio 1.208 [95% BCI 1.076 - 1.356], probability of superiority 0.999, estimated benefit [95% BCI] of 3.011 [1.134 - 5.41] days). Among those in the interim budesonide primary analysis who had the opportunity to contribute data for 28 days follow up, there were 59/692 (8.5%) COVID-19 related hospitalizations/deaths in the budesonide group vs 100/968 (10.3%) in the usual care group (estimated percentage benefit, 2.1% [95% BCI -0.7% - 4.8%], probability of superiority 0.928). CONCLUSIONS In this updated interim analysis, inhaled budesonide reduced time to recovery by a median of 3 days in people with COVID-19 with risk factors for adverse outcomes. Once 28 day follow up is complete for all participants randomized to budesonide, final analyses of time to recovery and hospitalization/death will be published. (Funded by the National Institute of Health Research/ United Kingdom Research Innovation [MC_PC_19079]; PRINCIPLE ISRCTN number, <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="isrctn" xlink:href="86534580">ISRCTN86534580</jats:ext-link>.)</jats:p>
Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: A modelling study
The diagnosis of hypertension has traditionally been based on blood-pressure measurements in the clinic, but home and ambulatory measurements better correlate with cardiovascular outcome, and ambulatory monitoring is more accurate than both clinic and home monitoring in diagnosing hypertension. We aimed to compare the cost-effectiveness of different diagnostic strategies for hypertension. We did a Markov model-based probabilistic cost-effectiveness analysis. We used a hypothetical primary-care population aged 40 years or older with a screening blood-pressure measurement greater than 140/90 mm Hg and risk-factor prevalence equivalent to the general population. We compared three diagnostic strategies - further blood pressure measurement in the clinic, at home, and with an ambulatory monitor - in terms of lifetime costs, quality-adjusted life years, and cost-effectiveness. Ambulatory monitoring was the most cost-effective strategy for the diagnosis of hypertension for men and women of all ages. It was cost-saving for all groups (from -£56 [95 CI -105 to -10] in men aged 75 years to -£323 [-389 to -222] in women aged 40 years) and resulted in more quality-adjusted life years for men and women older than 50 years (from 0·006 [0·000 to 0·015] for women aged 60 years to 0·022 [0·012 to 0·035] for men aged 70 years). This finding was robust when assessed with a wide range of deterministic sensitivity analyses around the base case, but was sensitive if home monitoring was judged to have equal test performance to ambulatory monitoring or if treatment was judged effective irrespective of whether an individual was hypertensive. Ambulatory monitoring as a diagnostic strategy for hypertension after an initial raised reading in the clinic would reduce misdiagnosis and save costs. Additional costs from ambulatory monitoring are counterbalanced by cost savings from better targeted treatment. Ambulatory monitoring is recommended for most patients before the start of antihypertensive drugs. National Institute for Health Research and the National Institute for Health and Clinical Excellence. © 2011 Elsevier Ltd.
Acute sinusitis is a common reason for patients to seek primary care consultations. The related impairment of daily functioning and quality of life is attributable to symptoms such as facial pain and nasal congestion. To assess the effectiveness of systemic corticosteroids in relieving symptoms of acute sinusitis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2011, which includes the Acute Respiratory Infections (ARI) Group's Specialised Register, the Database of Reviews of Effects (DARE) and the NHS Health Economics Database, MEDLINE (1966 to June week 2, 2011) and EMBASE (January 2009 to June 2011). Randomised controlled trials (RCTs) comparing systemic corticosteroids to placebo or standard clinical care for patients with acute sinusitis. Two review authors independently assessed methodological quality of the trials and extracted data. Four RCTs with a total of 1008 adult participants met our inclusion criteria. We judged studies to be of moderate methodological quality. Acute sinusitis was defined clinically in all trials. However, the three trials performed in ear, nose and throat (ENT) outpatient clinics also used radiological assessment as part of their inclusion criteria. All participants received oral antibiotics and were assigned to either oral corticosteroids (prednisone 24 mg to 80 mg daily or betamethasone 1 mg daily) or the control treatment (placebo in three trials and non-steroidal anti-inflammatory drugs (NSAIDs) in one trial). In all trials, participants treated with oral corticosteroids were more likely to have short-term resolution or improvement of symptoms than those receiving the control treatment: at Days 3 to 7, risk ratio (RR) 1.4, 95% CI 1.1 to 1.8; risk difference (RD) 20% (6% to 34%) and at Days 4 to 10 or 12, RR 1.3, 95% CI (1.0 to 1.7), RD 18% (3% to 33%). An analysis of the three trials with placebo as a control treatment showed similar results but with a lesser effect size: Days 3 to 6: RR 1.2, 95% CI (1.1 to 1.4), RD 12% (5% to 19%) and Days 4 to 10 or 12: RR 1.1, 95% CI (1.0 to 1.2), RD 10% (3% to 16%). Scenario analysis showed that outcomes missing from the trial reports might have introduced attrition bias (a worst-case scenario showed no statistically significant beneficial effect of oral corticosteroids). We did not identify any data on the long-term effects of oral corticosteroids on this condition, such as effects on relapse or recurrence rates. Reported side effects of oral corticosteroids were limited and mild. Current evidence suggests that oral corticosteroids as an adjunctive therapy to oral antibiotics are effective for short-term relief of symptoms in acute sinusitis. However, data are limited and there is a significant risk of bias. High quality trials assessing the efficacy of systemic corticosteroids both as an adjuvant and a monotherapy in primary care patients with acute sinusitis should be initiated.
BACKGROUND: The worldwide incidence of whooping cough (pertussis) has been estimated at 48.5 million cases and nearly 295,000 deaths per year. In low-income countries, the case-fatality rate among infants may be as high as 4%. Much of the morbidity of whooping cough in children and adults is due to the effects of the paroxysmal cough. Cough treatments proposed include corticosteroids, beta 2-adrenergic agonists, pertussis-specific immunoglobulin, antihistamines and possibly leukotriene receptor antagonists (LTRAs). OBJECTIVES: To assess the effectiveness and safety of interventions to reduce the severity of paroxysmal cough in whooping cough in children and adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register and the Database of Abstracts of Reviews of Effects (DARE); MEDLINE (1950 to March 2009); EMBASE (1980 to March 2009); AMED (1985 to March 2009); CINAHL (1982 to March 2009) and LILACS (March 2009). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs of any intervention (excluding antibiotics and vaccines) to suppress the cough in whooping cough. DATA COLLECTION AND ANALYSIS: Two review authors (SB, MT) independently selected trials, extracted data and assessed the quality of each trial. The primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis (turning blue), development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay. MAIN RESULTS: Ten trials were included of varying sample sizes (N = 9 to 135) from high-income countries. Study quality was generally poor. Included studies did not show a statistically significant benefit for any of the interventions. Diphenhydramine did not change coughing episodes; the mean difference of coughing spells per 24 hours was 1.9 (95% confidence interval (CI) - 4.7 to 8.5). One study on pertussis immunoglobulin reported a possible mean reduction of -3.1 whoops per 24 hours (95% CI -6.2 to 0.02) but no change in hospital stay (-0.7 days) (95% CI -3.8 to 2.4). Dexamethasone did not show a clear decrease in length of hospital stay (-3.5 days) (95% CI -15.3 to 8.4) and salbutamol showed no change in coughing paroxysms per 24 hours (-0.22) (95% CI -4.13 to 3.69). AUTHORS' CONCLUSIONS: Insufficient evidence exists to draw conclusions about the effects of interventions for the cough in whooping cough.
BACKGROUND: The introduction of portable monitors (point-of-care devices) for the management of patients on oral anticoagulation allows self-testing by the patient at home. Patients who self-test can either adjust their medication according to a pre-determined dose-INR schedule (self-management) or they can call a clinic to be told the appropriate dose adjustment (self-monitoring). Several trials of self-monitoring of oral anticoagulant therapy suggest this may be equal to or better than standard monitoring. OBJECTIVES: To evaluate the effects of self-monitoring or self-management of oral anticoagulant therapy compared to standard monitoring. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 4), MEDLINE, EMBASE and CINAHL (to November 2007). We checked bibliographies and contacted manufacturers and authors of relevant studies. No language restrictions were applied. SELECTION CRITERIA: Outcomes analysed were thromboembolic events, mortality, major haemorrhage, minor haemorrhage, tests in therapeutic range, frequency of testing, and feasibility of self-monitoring and self-management. DATA COLLECTION AND ANALYSIS: The review authors independently extracted data. We used a fixed-effect model with the Mantzel-Haenzel method to calculate the pooled risk ratio (RR) and Peto's method to verify the results for uncommon outcomes. We examined heterogeneity amongst studies with the Chi(2) and I(2) statistics. MAIN RESULTS: We identified 18 randomized trials (4723 participants). Pooled estimates showed significant reductions in both thromboembolic events (RR 0.50, 95% CI 0.36 to 0.69) and all-cause mortality (RR 0.64, 95% CI 0.46 to 0.89). This reduction in mortality remained significant after the removal of low-quality studies (RR 0.65, 95% CI 0.46 to 0.90). Trials of self-management alone showed significant reductions in thromboembolic events (RR 0.47, 95% CI 0.31 to 0.70) and all-cause mortality (RR 0.55, 95% CI 0.36 to 0.84); self-monitoring did not (thrombotic events RR 0.57, 95% CI 0.32 to 1.00; mortality RR 0.84, 95% CI 0.50 to 1.41). Self-monitoring significantly reduced major haemorrhages (RR 0.56, 95% CI 0.35 to 0.91) whilst self-management did not (RR 1.12, 95% CI 0.78 to 1.61). Twelve trials reported improvements in the percentage of mean INR measurements in the therapeutic range. No heterogeneity was identified in any of these comparisons. AUTHORS' CONCLUSIONS: Compared to standard monitoring, patients who self-monitor or self-manage can improve the quality of their oral anticoagulation therapy. The number of thromboembolic events and mortality were decreased without increases in harms. However, self-monitoring or self-management were not feasible for up to half of the patients requiring anticoagulant therapy. Reasons included patient refusal, exclusion by their general practitioner, and inability to complete training.
Backgrounds: During epidemic years, influenza attack rates in children exceed 40%. Options for prevention and treatment include the neuraminidase inhibitors: zanamivir and oseltamivir. Objectives: To assess the efficacy, safety and tolerability of neuraminidase inhibitors in the treatment and prevention of influenza infection in children. Search strategy: We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005); MEDLINE (1966 to April 2005); EMBASE (January 1980 to December 2004); the on-line GlaxoSmithKline Clinical Trials Register; the online Roche Clinical Trial Protocol Registry and Clinical Trial Results Database (August 2005); and reference lists of articles. We also scrutinised web sites of European and US regulatory bodies and contacted manufacturers and authors. Selection criteria: Double-blind, randomised, controlled trials comparing neuraminidase inhibitors with placebo or other antiviral drugs in children less than 12 years of age. Additional safety and tolerability data from other sources were also included. Data collection and analysis: Four authors applied the inclusion criteria to the retrieved studies, assessed trial quality and extracted data. Data were analysed separately for oseltamivir and zanamivir. Main results: Three trials involving 1500 children with a clinical case definition of influenza were included, of whom 977 had laboratory-confirmed influenza. Overall, trial quality was good. Oseltamivir reduced the median duration of illness by 26% (36 hours) in healthy children with laboratory-confirmed influenza (P value less than 0.0001). The reduction was only 7.7% (10 hours) in 'at risk' (asthmatic) children, and this did not reach statistical significance (P value = 0.54). Zanamivir reduced the median duration of illness by 24% (1.25 days) in healthy children with laboratory-confirmed influenza (P value less than 0.001). No data in 'at risk' children were available. Only oseltamivir produced a significant reduction in the complications of influenza (particularly otitis media), although there was a trend to benefit for zanamivir. We identified one randomised, controlled trial of oseltamivir for the prevention of influenza transmission in households, reporting data from 222 paediatric contacts. Where index cases had laboratory-confirmed influenza, a protective efficacy of 55% was observed, but this did not reach statistical significance (P value = 0.089). The adverse events profile of zanamivir was no worse than placebo, but vomiting was more common in children treated with oseltamivir. Authors' conclusions: Neuraminidase inhibitors are effective in shortening illness duration in healthy children with influenza, but efficacy in 'at risk' children remains to be proven. Oseltamivir is also effective in reducing the incidence of secondary complications, and may be effective for influenza prophylaxis. Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
BACKGROUND: Current methods of improving medication adherence for health problems are mostly complex, labour-intensive, and not reliably effective. Medication 'reminder packaging' which incorporates a date or time for a medication to be taken in the packaging, can act as a reminder system to improve adherence. OBJECTIVES: The objective of this review was to determine the effects of reminder packaging to enhance patient adherence with self-administered medications taken for one month or more. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library Issue 3, 2004), MEDLINE, EMBASE, CINAHL and PsycINFO from the start of the databases to 1 September 2004. We also searched the internet, contacted packaging manufacturers, and checked abstracts from the Pharm-line database and reference lists from relevant articles. We did not apply any language restrictions. SELECTION CRITERIA: We selected randomised controlled trials with at least 80% follow up, comparing a reminder packaging device with no device in participants taking self-administered medications for a minimum of one month. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed studies for inclusion, assessed quality, and extracted data from included studies. Where considered appropriate, data were combined for meta-analysis, or were reported and discussed in a narrative. MAIN RESULTS: Eight studies containing data on 1,137 participants were included. Six intervention groups in four trials provided data on the percentage of pills taken. Reminder packaging showed a significant increase in the percentage of pills taken, weighted mean difference 11% (95% confidence interval (CI) 6% to 17%). Notable heterogeneity occurred among these trials I(2 )= 96.3%. Two trials provided data for the proportion of self-reported adherent patients, reporting a reduction in the intervention group which was not statistically significant, odds ratio = 0.89 (95% CI 0.56 to 1.40). No appropriate data were available for meta-analysis of different clinical outcomes, the most common of these being blood pressure (three out of eight trials). Other clinical outcomes reported were glycated haemoglobin, serum Vitamin C and E levels, and self-reported psychological symptoms (one trial each). AUTHORS' CONCLUSIONS: Reminder packing may represent a simple method for improving adherence for patients with selected conditions examined to date. Further research is warranted to improve the design and targeting of these devices.