Showing papers by "Cochrane Collaboration published in 2014"

Oseltamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments.

Abstract: Objective To describe the potential benefits and harms of oseltamivir by reviewing all clinical study reports (or similar document when no clinical study report exists) of randomised placebo controlled trials and regulatory comments ("regulatory information"). Design Systematic review of regulatory information. Data sources Clinical study reports, trial registries, electronic databases, regulatory archives, and correspondence with manufacturers. Eligibility criteria for selecting studies Randomised placebo controlled trials on adults and children who had confirmed or suspected exposure to natural influenza. Main outcome measures Time to first alleviation of symptoms, influenza outcomes, complications, admissions to hospital, and adverse events in the intention to treat population. Results From the European Medicines Agency and Roche, we obtained clinical study reports for 83 trials. We included 23 trials in stage 1 (reliability and completeness screen) and 20 in stage 2 (formal analysis). In treatment trials on adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval 8.4 to 25.1 hours, P<0.001). There was no effect in children with asthma, but there was an effect in otherwise healthy children (mean difference 29 hours, 95% confidence interval 12 to 47 hours, P=0.001). In treatment trials there was no difference in admissions to hospital in adults (risk difference 0.15%, 95% confidence interval -0.91% to 0.78%, P=0.84) and sparse data in children and for prophylaxis. In adult treatment trials, oseltamivir reduced investigator mediated unverified pneumonia (risk difference 1.00%, 0.22% to 1.49%; number needed to treat to benefit (NNTB) 100, 95% confidence interval 67 to 451). The effect was not statistically significant in the five trials that used a more detailed diagnostic form for "pneumonia," and no clinical study reports reported laboratory or diagnostic confirmation of "pneumonia." The effect on unverified pneumonia in children and for prophylaxis was not significant. There was no significant reduction in risk of unverified bronchitis, otitis media, sinusitis, or any complication classified as serious or that led to study withdrawal. 14 of 20 trials prompted participants to self report all secondary illnesses to an investigator. Oseltamivir in the treatment of adults increased the risk of nausea (risk difference 3.66%, 0.90% to 7.39%; number needed to treat to harm (NNTH) 28, 95% confidence interval 14 to 112) and vomiting (4.56%, 2.39% to 7.58%; 22, 14 to 42). In treatment of children, oseltamivir induced vomiting (5.34%, 1.75% to 10.29%; 19, 10 to 57). In prophylaxis trials, oseltamivir reduced symptomatic influenza in participants by 55% (3.05%, 1.83% to 3.88%; NNTB 33, 26 to 55) and households (13.6%, 9.52% to 15.47%; NNTB 7, 6 to 11) based on one study, but there was no significant effect on.

Living systematic reviews: an emerging opportunity to narrow the evidence-practice gap

Abstract: The current difficulties in keeping systematic reviews up to date leads to considerable inaccuracy, hampering the translation of knowledge into action. Incremental advances in conventional review updating are unlikely to lead to substantial improvements in review currency. A new approach is needed. We propose living systematic review as a contribution to evidence synthesis that combines currency with rigour to enhance the accuracy and utility of health evidence. Living systematic reviews are high quality, up-to-date online summaries of health research, updated as new research becomes available, and enabled by improved production efficiency and adherence to the norms of scholarly communication. Together with innovations in primary research reporting and the creation and use of evidence in health systems, living systematic review contributes to an emerging evidence ecosystem.

Acupuncture-point stimulation for chemotherapy-induced nausea or vomiting

Abstract: BACKGROUND There have been recent advances in chemotherapy-induced nausea and vomiting using 5-HT(3) inhibitors and dexamethasone. However, many still experience these symptoms, and expert panels encourage additional methods to reduce these symptoms. OBJECTIVES The objective was to assess the effectiveness of acupuncture-point stimulation on acute and delayed chemotherapy-induced nausea and vomiting in cancer patients. SEARCH STRATEGY We searched MEDLINE, EMBASE, PsycLIT, MANTIS, Science Citation Index, CCTR (Cochrane Controlled Trials Registry), Cochrane Complementary Medicine Field Trials Register, Cochrane Pain, Palliative Care and Supportive Care Specialized Register, Cochrane Cancer Specialized Register, and conference abstracts. SELECTION CRITERIA Randomized trials of acupuncture-point stimulation by any method (needles, electrical stimulation, magnets, or acupressure) and assessing chemotherapy-induced nausea or vomiting, or both. DATA COLLECTION AND ANALYSIS Data were provided by investigators of the original trials and pooled using a fixed effect model. Relative risks were calculated on dichotomous data. Standardized mean differences were calculated for nausea severity. Weighted mean differences were calculated for number of emetic episodes. MAIN RESULTS Eleven trials (N = 1247) were pooled. Overall, acupuncture-point stimulation of all methods combined reduced the incidence of acute vomiting (RR = 0.82; 95% confidence interval 0.69 to 0.99; P = 0.04), but not acute or delayed nausea severity compared to control. By modality, stimulation with needles reduced proportion of acute vomiting (RR = 0.74; 95% confidence interval 0.58 to 0.94; P = 0.01), but not acute nausea severity. Electroacupuncture reduced the proportion of acute vomiting (RR = 0.76; 95% confidence interval 0.60 to 0.97; P = 0.02), but manual acupuncture did not; delayed symptoms for acupuncture were not reported. Acupressure reduced mean acute nausea severity (SMD = -0.19; 95% confidence interval -0.37 to -0.01; P = 0.04) but not acute vomiting or delayed symptoms. Noninvasive electrostimulation showed no benefit for any outcome. All trials used concomitant pharmacologic antiemetics, and all, except electroacupuncture trials, used state-of-the-art antiemetics. AUTHORS' CONCLUSIONS This review complements data on post-operative nausea and vomiting suggesting a biologic effect of acupuncture-point stimulation. Electroacupuncture has demonstrated benefit for chemotherapy-induced acute vomiting, but studies combining electroacupuncture with state-of-the-art antiemetics and in patients with refractory symptoms are needed to determine clinical relevance. Self-administered acupressure appears to have a protective effect for acute nausea and can readily be taught to patients though studies did not involve placebo control. Noninvasive electrostimulation appears unlikely to have a clinically relevant impact when patients are given state-of-the-art pharmacologic antiemetic therapy.

Investigation of publication bias in meta-analyses of diagnostic test accuracy: a meta-epidemiological study

Abstract: The validity of a meta-analysis can be understood better in light of the possible impact of publication bias. The majority of the methods to investigate publication bias in terms of small study-effects are developed for meta-analyses of intervention studies, leaving authors of diagnostic test accuracy (DTA) systematic reviews with limited guidance. The aim of this study was to evaluate if and how publication bias was assessed in meta-analyses of DTA, and to compare the results of various statistical methods used to assess publication bias. A systematic search was initiated to identify DTA reviews with a meta-analysis published between September 2011 and January 2012. We extracted all information about publication bias from the reviews and the two-by-two tables. Existing statistical methods for the detection of publication bias were applied on data from the included studies. Out of 1,335 references, 114 reviews could be included. Publication bias was explicitly mentioned in 75 reviews (65.8%) and 47 of these had performed statistical methods to investigate publication bias in terms of small study-effects: 6 by drawing funnel plots, 16 by statistical testing and 25 by applying both methods. The applied tests were Egger’s test (n = 18), Deeks’ test (n = 12), Begg’s test (n = 5), both the Egger and Begg tests (n = 4), and other tests (n = 2). Our own comparison of the results of Begg’s, Egger’s and Deeks’ test for 92 meta-analyses indicated that up to 34% of the results did not correspond with one another. The majority of DTA review authors mention or investigate publication bias. They mainly use suboptimal methods like the Begg and Egger tests that are not developed for DTA meta-analyses. Our comparison of the Begg, Egger and Deeks tests indicated that these tests do give different results and thus are not interchangeable. Deeks’ test is recommended for DTA meta-analyses and should be preferred.

Impact of Spin in the Abstracts of Articles Reporting Results of Randomized Controlled Trials in the Field of Cancer: The SPIIN Randomized Controlled Trial

Abstract: Purpose We aimed to assess the impact of spin (ie, reporting to convince readers that the beneficial effect of the experimental treatment is greater than shown by the results) on the interpretation of results of abstracts of randomized controlled trials (RCTs) in the field of cancer. Methods We performed a two-arm, parallel-group RCT. We selected a sample of published RCTs with statistically nonsignificant primary outcome and with spin in the abstract conclusion. Two versions of these abstracts were used—the original with spin and a rewritten version without spin. Participants were clinician corresponding authors of articles reporting RCTs, investigators of trials, and reviewers of French national grants. The primary outcome was clinicians' interpretation of the beneficial effect of the experimental treatment (0 to 10 scale). Participants were blinded to study hypothesis. Results Three hundred clinicians were randomly assigned using a Web-based system; 150 clinicians assessed an abstract with spin and 150...

Interventions to improve return to work in depressed people

Abstract: Background Work disability such as sickness absence is common in people with depression. Objectives To evaluate the effectiveness of interventions aimed at reducing work disability in employees with depressive disorders. Search methods We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, CINAHL, and PsycINFO until January 2014. Selection criteria We included randomised controlled trials (RCTs) and cluster RCTs of work-directed and clinical interventions for depressed people that included sickness absence as an outcome. Data collection and analysis Two authors independently extracted the data and assessed trial quality. We used standardised mean differences (SMDs) with 95% confidence intervals (CIs) to pool study results in the studies we judged to be sufficiently similar. We used GRADE to rate the quality of the evidence. Main results We included 23 studies with 26 study arms, involving 5996 participants with either a major depressive disorder or a high level of depressive symptoms. We judged 14 studies to have a high risk of bias and nine to have a low risk of bias. Work-directed interventions We identified five work-directed interventions. There was moderate quality evidence that a work-directed intervention added to a clinical intervention reduced sickness absence (SMD -0.40; 95% CI -0.66 to -0.14; 3 studies) compared to a clinical intervention alone. There was moderate quality evidence based on a single study that enhancing the clinical care in addition to regular work-directed care was not more effective than work-directed care alone (SMD -0.14; 95% CI -0.49 to 0.21). There was very low quality evidence based on one study that regular care by occupational physicians that was enhanced with an exposure-based return to work program did not reduce sickness absence compared to regular care by occupational physicians (non-significant finding: SMD 0.45; 95% CI -0.00 to 0.91). Clinical interventions, antidepressant medication Three studies compared the effectiveness of selective serotonin reuptake inhibitor (SSRI) to selective norepinephrine reuptake inhibitor (SNRI) medication on reducing sickness absence and yielded highly inconsistent results. Clinical interventions, psychological We found moderate quality evidence based on three studies that telephone or online cognitive behavioural therapy was more effective in reducing sick leave than usual primary or occupational care (SMD -0.23; 95% CI -0.45 to -0.01). Clinical interventions, psychological combined with antidepressant medication We found low quality evidence based on two studies that enhanced primary care did not substantially decrease sickness absence in the medium term (4 to 12 months) (SMD -0.02; 95% CI -0.15 to 0.12). A third study found no substantial effect on sickness absence in favour of this intervention in the long term (24 months). We found high quality evidence, based on one study, that a structured telephone outreach and care management program was more effective in reducing sickness absence than usual care (SMD - 0.21; 95% CI -0.37 to -0.05). Clinical interventions, exercise We found low quality evidence based on one study that supervised strength exercise reduced sickness absence compared to relaxation (SMD -1.11; 95% CI -1.68 to -0.54). We found moderate quality evidence based on two studies that aerobic exercise was no more effective in reducing sickness absence than relaxation or stretching (SMD -0.06; 95% CI -0.36 to 0.24). Authors' conclusions We found moderate quality evidence that adding a work-directed intervention to a clinical intervention reduced the number of days on sick leave compared to a clinical intervention alone. We also found moderate quality evidence that enhancing primary or occupational care with cognitive behavioural therapy reduced sick leave compared to the usual care. A structured telephone outreach and care management program that included medication reduced sickness absence compared to usual care. However, enhancing primary care with a quality improvement program did not have a considerable effect on sickness absence. There was no evidence of a difference in effect on sickness absence of one antidepressant medication compared to another. More studies are needed on work-directed interventions. Clinical intervention studies should also include work outcomes to increase our knowledge on reducing sickness absence in depressed workers.

Neuraminidase inhibitors for preventing and treating influenza in adults and children

Abstract: © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Background: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. Objectives: To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments. Search methods: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database. Selection criteria: Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza. Data collection and analysis: We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers. Main results: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants). Inadequate reporting put most of the zanamivir studies and half of the oseltamivir studies at a high risk of selection bias. There were inadequate measures in place to protect 11 studies of oseltamivir from performance bias due to non-identical presentation of placebo. Attrition bias was high across the oseltamivir studies and there was also evidence of selective reporting for both the zanamivir and oseltamivir studies. The placebo interventions in both sets of trials may have contained active substances. Time to first symptom alleviation. For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P 1000) and nausea whilst on treatment (RD 4.15%, 95% CI 0.86 to 9.51); NNTH = 25 (95% CI 11 to 116). Authors' conclusions: Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions. The use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults and vomiting in children. The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir. The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza. The influenza virus-specific mechanism of action proposed by the producers does not fit the clinical evidence.

Metformin treatment before and during IVF or ICSI in women with polycystic ovary syndrome

Abstract: Background The use of insulin-sensitising agents, such as metformin, in women with polycystic ovary syndrome (PCOS) who are undergoing ovulation induction or in vitro fertilisation (IVF) cycles has been widely studied. Metformin reduces hyperinsulinaemia and suppresses the excessive ovarian production of androgens. As a consequence, it is suggested that metformin could improve assisted reproductive techniques (ART) outcomes, such as ovarian hyperstimulation syndrome (OHSS), pregnancy and live birth rates. Objectives To determine the effectiveness and safety of metformin as a co-treatment during IVF or intracytoplasmic sperm injection (ICSI) in achieving pregnancy or live birth in women with PCOS. Search methods We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, LILACS, the metaRegister of Controlled Trials and reference lists of articles (up to 15 October 2014). Selection criteria Types of studies: randomised controlled trials (RCTs) comparing metformin treatment with placebo or no treatment in women with PCOS who underwent IVF or ICSI treatment. Types of participants: women of reproductive age with anovulation due to PCOS with or without co-existing infertility factors. Types of interventions: metformin administered before and during IVF or ICSI treatment. Types of outcome measures: live birth rate, clinical pregnancy rate, miscarriage rate, incidence of ovarian hyperstimulation syndrome , incidence of participant-reported side effects, serum oestradiol level on the day of trigger, serum androgen level, and fasting insulin and glucose levels. Data collection and analysis Two review authors independently selected the studies, extracted the data according to the protocol and assessed study quality. The overall quality of the evidence was assessed using GRADE methods. Main results We included nine randomised controlled trials involving a total of 816 women with PCOS. When metformin was compared with placebo there was no clear evidence of a difference between the groups in live birth rates (OR 1.39, 95% CI 0.81 to 2.40, five RCTs, 551 women, I2 = 52%, low-quality evidence). Our findings suggest that for a woman with a 32 % chance of achieving a live birth using placebo, the corresponding chance using metformin treatment would be between 28% and 53%. When metformin was compared with placebo or no treatment, clinical pregnancy rates were higher in the metformin group (OR 1.52; 95% CI 1.07 to 2.15; eight RCTs, 775 women, I2 = 18%, moderate-quality evidence). This suggests that for a woman with a 31% chance of achieving a clinical pregnancy using placebo or no treatment, the corresponding chance using metformin treatment would be between 32% and 49%. The risk of ovarian hyperstimulation syndrome was lower in the metformin group (OR 0.29; 95% CI 0.18 to 0.49, eight RCTs, 798 women, I2 = 11%, moderate-quality evidence). This suggests that for a woman with a 27% risk of having OHSS without metformin the corresponding chance using metformin treatment would be between 6% and 15%. Side effects (mostly gastrointestinal) were more common in the metformin group (OR 4.49, 95% CI 1.88 to 10.72, for RCTs, 431 women, I2=57%, low quality evidence) The overall quality of the evidence was moderate for the outcomes of clinical pregnancy, OHSS and miscarriage, and low for other outcomes. The main limitations in the evidence were imprecision and inconsistency. Authors' conclusions This review found no conclusive evidence that metformin treatment before or during ART cycles improved live birth rates in women with PCOS. However, the use of this insulin-sensitising agent increased clinical pregnancy rates and decreased the risk of OHSS.

COREQ (Consolidated Criteria for Reporting Qualitative Studies)

Abstract: The Consolidated Criteria for Reporting Qualitative Studies (COREQ) covers the reporting of studies using interviews and focus groups It is the only reporting guidance for qualitative research to have received other than isolated endorsement although it applies to only a few of the many qualitative methods in use The COREQ checklist was developed to promote explicit and comprehensive reporting of interviews and focus groups The COREQ checklist consists of 32 criteria, with a descriptor to supplement each item This chapter discusses how best to use the guideline, development process, evidence of the effectiveness of guideline, endorsement and adherence, cautions and limitations, and key features of the COREQ It is important that researchers provide sufficient detail on their methods of data analysis and the relationship between the analysis and the findings in the research report so that reviewers can assess the rigor of the analysis and the credibility of the findings

Study flow diagrams in Cochrane systematic review updates: an adapted PRISMA flow diagram.

Abstract: Cochrane systematic reviews are conducted and reported according to rigorous standards. A study flow diagram must be included in a new review, and there is clear guidance from the PRISMA statement on how to do this. However, for a review update, there is currently no guidance on how study flow diagrams should be presented. To address this, a working group was formed to find a solution and produce guidance on how to use these diagrams in review updates.A number of different options were devised for how these flow diagrams could be used in review updates, and also in cases where multiple searches for a review or review update have been conducted. These options were circulated to the Cochrane information specialist community for consultation and feedback. Following the consultation period, the working group refined the guidance and made the recommendation that for review updates an adapted PRISMA flow diagram should be used, which includes an additional box with the number of previously included studies feeding into the total. Where multiple searches have been conducted, the results should be added together and treated as one set of results.There is no existing guidance for using study flow diagrams in review updates. Our adapted diagram is a simple and pragmatic solution for showing the flow of studies in review updates.

A systematic review of the Robson classification for caesarean section: what works, doesn't work and how to improve it.

Abstract: Background Caesarean sections (CS) rates continue to increase worldwide without a clear understanding of the main drivers and consequences. The lack of a standardized internationally-accepted classification system to monitor and compare CS rates is one of the barriers to a better understanding of this trend. The Robson's 10-group classification is based on simple obstetrical parameters (parity, previous CS, gestational age, onset of labour, fetal presentation and number of fetuses) and does not involve the indication for CS. This classification has become very popular over the last years in many countries. We conducted a systematic review to synthesize the experience of users on the implementation of this classification and proposed adaptations. Methods Four electronic databases were searched. A three-step thematic synthesis approach and a qualitative metasummary method were used. Results 232 unique reports were identified, 97 were selected for full-text evaluation and 73 were included. These publications reported on the use of Robson's classification in over 33 million women from 31 countries. According to users, the main strengths of the classification are its simplicity, robustness, reliability and flexibility. However, missing data, misclassification of women and lack of definition or consensus on core variables of the classification are challenges. To improve the classification for local use and to decrease heterogeneity within groups, several subdivisions in each of the 10 groups have been proposed. Group 5 (women with previous CS) received the largest number of suggestions. Conclusions The use of the Robson classification is increasing rapidly and spontaneously worldwide. Despite some limitations, this classification is easy to implement and interpret. Several suggested modifications could be useful to help facilities and countries as they work towards its implementation.

Extent of non-publication in cohorts of studies approved by research ethics committees or included in trial registries.

Abstract: Background The synthesis of published research in systematic reviews is essential when providing evidence to inform clinical and health policy decision-making. However, the validity of systematic reviews is threatened if journal publications represent a biased selection of all studies that have been conducted (dissemination bias). To investigate the extent of dissemination bias we conducted a systematic review that determined the proportion of studies published as peer-reviewed journal articles and investigated factors associated with full publication in cohorts of studies (i) approved by research ethics committees (RECs) or (ii) included in trial registries.

Tonsillectomy or adenotonsillectomy versus non‐surgical treatment for chronic/recurrent acute tonsillitis

Abstract: Background Surgical removal of the tonsils, with or without adenoidectomy (adeno-/tonsillectomy), is a common ENT operation, but th e indicationsfor surgery are controversial. This is an update of a Cochrane re view first published in The Cochrane Library in Issue 3, 1999 andpreviously updated in 2009. Objectives To assess the effectiveness of tonsillectomy (with and without adenoidectomy) in children and adults with chr onic/recurrent acutetonsillitis in reducing the number and severity of episodes of tonsillitis or sore throat. Search methods We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials(CENTRAL); PubMed; EMBASE; CINAHL; Web of S cie nce; Cambridge Scientific Abstracts; ISRCTN and additional sources forpublished and unpublished trials. The date of the most recent search was 30 June 2014. Selection criteria Randomised controlled trials comparing tonsillectomy (with or without adenoidectomy) with non-surgical treatment in adults andchildren with chronic/recurrent acute tonsillitis. Data collection and analysis We used the standard methodological procedures expected by The Cochrane Collaboration.

Aquatic exercise training for fibromyalgia

Abstract: Background Exercise training is commonly recommended for individuals with fibromyalgia. This review examined the effects of supervised group aquatic training programs (led by an instructor). We defined aquatic training as exercising in a pool while standing at waist, chest, or shoulder depth. This review is part of the update of the 'Exercise for treating fibromyalgia syndrome' review first published in 2002, and previously updated in 2007. Objectives The objective of this systematic review was to evaluate the benefits and harms of aquatic exercise training in adults with fibromyalgia. Search methods We searched The Cochrane Library 2013, Issue 2 (Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, NHS Economic Evaluation Database), MEDLINE, EMBASE, CINAHL, PEDro, Dissertation Abstracts, WHO international Clinical Trials Registry Platform, and AMED, as well as other sources (i.e., reference lists from key journals, identified articles, meta-analyses, and reviews of all types of treatment for fibromyalgia) from inception to October 2013. Using Cochrane methods, we screened citations, abstracts, and full-text articles. Subsequently, we identified aquatic exercise training studies. Selection criteria Selection criteria were: a) full-text publication of a randomized controlled trial (RCT) in adults diagnosed with fibromyalgia based on published criteria, and b) between-group data for an aquatic intervention and a control or other intervention. We excluded studies if exercise in water was less than 50% of the full intervention. Data collection and analysis We independently assessed risk of bias and extracted data (24 outcomes), of which we designated seven as major outcomes: multidimensional function, self reported physical function, pain, stiffness, muscle strength, submaximal cardiorespiratory function, withdrawal rates and adverse effects. We resolved discordance through discussion. We evaluated interventions using mean differences (MD) or standardized mean differences (SMD) and 95% confidence intervals (95% CI). Where two or more studies provided data for an outcome, we carried out meta-analysis. In addition, we set and used a 15% threshold for calculation of clinically relevant differences. Main results We included 16 aquatic exercise training studies (N = 881; 866 women and 15 men). Nine studies compared aquatic exercise to control, five studies compared aquatic to land-based exercise, and two compared aquatic exercise to a different aquatic exercise program. We rated the risk of bias related to random sequence generation (selection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), blinding of outcome assessors (detection bias), and other bias as low. We rated blinding of participants and personnel (selection and performance bias) and allocation concealment (selection bias) as low risk and unclear. The assessment of the evidence showed limitations related to imprecision, high statistical heterogeneity, and wide confidence intervals. Aquatic versus control We found statistically significant improvements (P value < 0.05) in all of the major outcomes. Based on a 100-point scale, multidimensional function improved by six units (MD -5.97, 95% CI -9.06 to -2.88; number needed to treat (NNT) 5, 95% CI 3 to 9), self reported physical function by four units (MD -4.35, 95% CI -7.77 to -0.94; NNT 6, 95% CI 3 to 22), pain by seven units (MD -6.59, 95% CI -10.71 to -2.48; NNT 5, 95% CI 3 to 8), and stiffness by 18 units (MD -18.34, 95% CI -35.75 to -0.93; NNT 3, 95% CI 2 to 24) more in the aquatic than the control groups. The SMD for muscle strength as measured by knee extension and hand grip was 0.63 standard deviations higher compared to the control group (SMD 0.63, 95% CI 0.20 to 1.05; NNT 4, 95% CI 3 to 12) and cardiovascular submaximal function improved by 37 meters on six-minute walk test (95% CI 4.14 to 69.92). Only two major outcomes, stiffness and muscle strength, met the 15% threshold for clinical relevance (improved by 27% and 37% respectively). Withdrawals were similar in the aquatic and control groups and adverse effects were poorly reported, with no serious adverse effects reported. Aquatic versus land-based There were no statistically significant differences between interventions for multidimensional function, self reported physical function, pain or stiffness: 0.91 units (95% CI -4.01 to 5.83), -5.85 units (95% CI -12.33 to 0.63), -0.75 units (95% CI -10.72 to 9.23), and two units (95% CI -8.88 to 1.28) respectively (all based on a 100-point scale), or in submaximal cardiorespiratory function (three seconds on a 100-meter walk test, 95% CI -1.77 to 7.77). We found a statistically significant difference between interventions for strength, favoring land–based training (2.40 kilo pascals grip strength, 95% CI 4.52 to 0.28). None of the outcomes in the aquatic versus land comparison reached clinically relevant differences of 15%. Withdrawals were similar in the aquatic and land groups and adverse effects were poorly reported, with no serious adverse effects in either group. Aquatic versus aquatic (Ai Chi versus stretching in the water, exercise in pool water versus exercise in sea water) Among the major outcomes the only statistically significant difference between interventions was for stiffness, favoring Ai Chi (1.00 on a 100-point scale, 95% CI 0.31 to 1.69). Authors' conclusions Low to moderate quality evidence relative to control suggests that aquatic training is beneficial for improving wellness, symptoms, and fitness in adults with fibromyalgia. Very low to low quality evidence suggests that there are benefits of aquatic and land-based exercise, except in muscle strength (very low quality evidence favoring land). No serious adverse effects were reported.

Guidance for updating clinical practice guidelines: a systematic review of methodological handbooks

Abstract: Updating clinical practice guidelines (CPGs) is a crucial process for maintaining the validity of recommendations. Methodological handbooks should provide guidance on both developing and updating CPGs. However, little is known about the updating guidance provided by these handbooks. We conducted a systematic review to identify and describe the updating guidance provided by CPG methodological handbooks and included handbooks that provide updating guidance for CPGs. We searched in the Guidelines International Network library, US National Guidelines Clearinghouse and MEDLINE (PubMed) from 1966 to September 2013. Two authors independently selected the handbooks and extracted the data. We used descriptive statistics to analyze the extracted data and conducted a narrative synthesis. We included 35 handbooks. Most handbooks (97.1%) focus mainly on developing CPGs, including variable degrees of information about updating. Guidance on identifying new evidence and the methodology of assessing the need for an update is described in 11 (31.4%) and eight handbooks (22.8%), respectively. The period of time between two updates is described in 25 handbooks (71.4%), two to three years being the most frequent (40.0%). The majority of handbooks do not provide guidance for the literature search, evidence selection, assessment, synthesis, and external review of the updating process. Guidance for updating CPGs is poorly described in methodological handbooks. This guidance should be more rigorous and explicit. This could lead to a more optimal updating process, and, ultimately to valid trustworthy guidelines.

Reporting of results from network meta-analyses: methodological systematic review.

Abstract: Objective To examine how the results of network meta-analyses are reported. Design Methodological systematic review of published reports of network meta-analyses. Data sources Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Medline, and Embase, searched from inception to 12 July 2012. Study selection All network meta-analyses comparing the clinical efficacy of three or more interventions in randomised controlled trials were included, excluding meta-analyses with an open loop network of three interventions. Data extraction and synthesis The reporting of the network and results was assessed. A composite outcome included the description of the network (number of interventions, direct comparisons, and randomised controlled trials and patients for each comparison) and the reporting of effect sizes derived from direct evidence, indirect evidence, and the network meta-analysis. Results 121 network meta-analyses (55 published in general journals; 48 funded by at least one private source) were included. The network and its geometry (network graph) were not reported in 100 (83%) articles. The effect sizes derived from direct evidence, indirect evidence, and the network meta-analysis were not reported in 48 (40%), 108 (89%), and 43 (36%) articles, respectively. In 52 reports that ranked interventions, 43 did not report the uncertainty in ranking. Overall, 119 (98%) reports of network meta-analyses did not give a description of the network or effect sizes from direct evidence, indirect evidence, and the network meta-analysis. This finding did not differ by journal type or funding source. Conclusions The results of network meta-analyses are heterogeneously reported. Development of reporting guidelines to assist authors in writing and readers in critically appraising reports of network meta-analyses is timely.

Chlorpromazine versus placebo for schizophrenia

Abstract: Background Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia. Objectives To evaluate the effects of chlorpromazine for schizophrenia in comparison with placebo. Search strategy We updated previous searches of the Cochrane Schizophrenia Group Register (October 1999), Biological Abstracts (1982-1995), the Cochrane Library (1999, Issue 2), EMBASE (1980-1995), MEDLINE (1966-1995) and PsycLIT (1974-1995), by searching Cochrane Schizophrenia Group Register (June 2002). References of all identified studies were searched for further trial citations. Pharmaceutical companies and authors of trials were contacted. Selection criteria All randomised controlled trials (RCTs) comparing chlorpromazine with placebo relevant to people with schizophrenia, and non-affective serious/chronic mental illness irrespective of mode of diagnosis. Primary outcomes of interest were death, violent behaviours, overall improvement, relapse and satisfaction with care. Data collection and analysis Citations and, where possible, abstracts were inspected independently by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted by BT and JR. CA and GA independently checked a 10% sample for reliability. Dichotomous data were analysed using random effects relative risk (RR) and the 95% confidence interval (CI) around this was estimated. Where possible the number needed to treat (NNT) or number needed to harm statistics (NNH) were calculated. Continuous data were excluded if more than 50% of people were lost to follow up, but, where possible, weighted mean difference (WMD) was calculated. Main results Over 1000 electronic records were inspected. The review currently mentions 302 papers in its Excluded Studies table and 50 studies in its Included Studies table. Four papers are awaiting translation. Chlorpromazine reduces relapse over six months to two years (n=512, 3 RCTs, RR 0.65 CI 0.5 to 0.9, NNT 3 CI 2.5 to 4) and promotes a global improvement in a person's symptoms and functioning (n=1121, 13 RCTs, RR no change/not improved 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10) although the placebo response is also considerable. Fewer people allocated to chlorpromazine leave trials early (n=1755, 25 RCTs, RR 0.77 CI 0.6 to 1.1) but the difference is not statistically significant. There are many adverse effects. Chlorpromazine is clearly sedating (n=1404, 19 RCTs, RR 2.65 CI 1.9 to 3.7, NNH 5 CI 4 to 6), it increases a person's chances of experiencing acute movement disorders (n=942, 5 RCTs, RR 3.38 CI 1.4 to 8.0, NNH 22 CI 15 to 46), parkinsonism (n=1265, 12 RCTs, RR 2.56 CI 1.2 to 5.4, NNH 10 CI 8 to 16) and, perhaps, fits (n=695, 3 RCTs, RR 2.41 CI 0.4 to 16). Amongst other things it clearly causes a lowering of blood pressure with accompanying dizziness (n=1394, 16 RCTs, RR 2.10 CI 1.5 to 2.8, NNH 10 CI 8 to 15) and considerable increases in weight (n=165, 5 RCTs, RR 4.44 CI 2.1 to 9, NNH 3 CI 2 to 5). Authors' conclusions This review will confirm much that clinicians and recipients of care already know, but provides quantification to support clinical impression. Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by this review. Chlorpromazine, in common use for half a century, is a well established but imperfect treatment. Judicious use of this best available evidence should lead to improved evidence-based decision making by clinicians, carers and patients.

Pregnancy outcomes after assisted human reproduction.

Abstract: Objective To review the effect of assisted human reproduction (AHR) on perinatal outcomes, to identify areas requiring further research with regard to birth outcomes and AHR, and to provide guidelines to optimize obstetrical management and counselling of prospective Canadian parents. Outcomes This document compares perinatal outcomes of different types of AHR pregnancies with each other and with those of spontaneously conceived pregnancies. Clinicians will be better informed about the adverse outcomes that have been documented in association with AHR, including obstetrical complications, adverse perinatal outcomes, multiple gestations, structural congenital abnormalities, chromosomal abnormalities, and imprinting disorders. Evidence Published literature was retrieved through searches of MEDLINE and the Cochrane Library from January 2005 to December 2012 using appropriate controlled vocabulary and key words (assisted reproduction, assisted reproductive technology, ovulation induction, intracytoplasmic sperm injection, embryo transfer, and in vitro fertilization). Results were not restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies; studies of all designs published in English from January 2005 to December 2012 were reviewed, and additional publications were identified from the bibliographies of these articles. Searches were updated on a regular basis and incorporated in the guideline to August 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1).

Aerobic physical exercise for adult patients with haematological malignancies

Abstract: Background Although people with haematological malignancies have to endure long phases of therapy and immobility which is known to diminish their physical performance level, the advice to rest and avoid intensive exercises is still common practice. This recommendation is partly due to the severe anaemia and thrombocytopenia from which many patients suffer. The inability to perform activities of daily living restricts them, diminishes their quality of life and can influence medical therapy. Objectives To evaluate the efficacy, safety and feasibility of aerobic physical exercise for adults suffering from haematological malignancies. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2014, Issue 1) and MEDLINE (1950 to January 2014) as well as conference proceedings for randomised controlled trials (RCTs). Selection criteria We included RCTs comparing an aerobic physical exercise intervention, intending to improve the oxygen system, in addition to standard care with standard care only for adults suffering from haematological malignancies. We also included studies that evaluated aerobic exercise in addition to strength training. We excluded studies that investigated the effect of training programmes that were composed of yoga, tai chi chuan, qigong or similar types of exercise. We also excluded studies exploring the influence of strength training without additive aerobic exercise. Additionally, we excluded studies assessing outcomes without any clinical impact. Data collection and analysis Two review authors independently screened search results, extracted data and assessed the quality of trials. We used risk ratios (RRs) for adverse events and 100-day survival, standardised mean differences for quality of life (QoL), fatigue, and physical performance, and mean differences for anthropometric measurements. Main results Our search strategies identified 1518 potentially relevant references. Of these, we included nine RCTs involving 818 participants. The potential risk of bias in these trials is unclear, due to poor reporting. The majority of participants suffered from acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), malignant lymphoma and multiple myeloma, and six trials randomised people receiving stem cell transplantation. Mostly, the exercise intervention consisted of various walking intervention programmes with different duration and intensity levels. Our primary endpoint of overall survival (OS) was not analysed in any of the included trials, but three trials reported deceased participants during the course of the study or during the first 100 days. There is no evidence for a difference between participants exercising and those in the control group (RR 0.93; 95% CI 0.59 to 1.47; P = 0.75; 3 trials, 269 participants, moderate quality of evidence). Four trials analysed the influence of exercise intervention on quality of life (QoL). Excluding one trial with serious baseline imbalances, physical exercise improves QoL (SMD 0.26; 95% CI 0.03 to 0.49; P = 0.03; 3 trials, 291 participants, low quality of evidence). This positive effect of exercise was also found in the subscales physical functioning (SMD 0.33; 95% CI 0.13 to 0.52; P = 0.0009; 4 trials, 422 participants, moderate quality of evidence) and depression (SMD 0.25; 95% CI -0.00 to 0.50; P = 0.05; 3 trials, 249 participants, low quality of evidence). However, there is no evidence for a difference between additional exercise and standard treatment for the subscale anxiety (SMD -0.18; 95% CI -0.64 to 0.28; P = 0.45; 3 trials, 249 participants, low quality of evidence). Seven trials (692 participants) evaluated fatigue. There is moderate quality of evidence that exercise improves fatigue (SMD 0.24; 95% CI 0.08 to 0.40; P = 0.003). Eight studies evaluated various aspects of physical performance (e.g. aerobic capacity, cardiovascular fitness), but none of them could be pooled in a meta-analysis. In seven trials there is a tendency or statistically significant effect favouring the exercise group (very low quality of evidence). Three trials (266 participants) investigated serious adverse events (SAEs) (e.g. bleeding, fever, pneumonia, deep vein thrombosis, and infection), and one trial (122 participants) assessed adverse events (AEs). There is no evidence for a difference between arms in terms of SAEs (RR 1.44; 95% CI 0.96 to 2.18; P = 0.06) or AEs (RR 7.23; 95% CI 0.38 to 137.05; P = 0.19); both findings are based on low quality of evidence. Authors' conclusions There is no evidence for differences in mortality between the exercise and control groups. Physical exercise added to standard care can improve quality of life, especially physical functioning, depression and fatigue. Currently, there is inconclusive evidence regarding anxiety, physical performance, serious adverse events and adverse events. We need further trials with more participants and longer follow-up periods to evaluate the effects of exercise intervention for people suffering from haematological malignancies. Furthermore, we need trials with overall survival as the primary outcome to determine whether the suggested benefits will translate into a survival advantage. To enhance comparability of study data, development and implementation of core sets of measuring devices would be helpful.

Tonsillectomy for periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA)

Abstract: Background Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is a rare clinical syndrome of unknown cause usually identified in children. Tonsillectomy is considered a potential treatment option for this syndrome. This is an update of a Cochrane Review first published in 2010 and previously updated in 2014. Objectives To assess the effectiveness and safety of tonsillectomy (with or without adenoidectomy) compared with non-surgical treatment in the management of children with PFAPA. Search methods The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2019, Issue 4); PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 15 October 2019. Selection criteria Randomised controlled trials comparing tonsillectomy (with or without adenoidectomy) with non-surgical treatment in children with PFAPA. Data collection and analysis We used the standard methodological procedures expected by Cochrane. The primary outcomes were the proportion of children whose symptoms have completely resolved and complications of surgery (haemorrhage and number of days of postoperative pain). Secondary outcomes were: number of episodes of fever and the associated symptoms; severity of episodes; use of corticosteroids; absence or time off school; quality of life. We used GRADE to assess the certainty of the evidence for each outcome. Main results Two trials were included with a total of 67 children randomised (65 analysed); we judged both to be at low risk of bias. One trial of 39 participants recruited children with PFAPA syndrome diagnosed according to rigid, standard criteria. The trial compared adenotonsillectomy to watchful waiting and followed up patients for 18 months. A smaller trial of 28 children applied less stringent criteria for diagnosing PFAPA and probably also included participants with alternative types of recurrent pharyngitis. This trial compared tonsillectomy alone to no treatment and followed up patients for six months. Combining the trial results suggests that patients with PFAPA likely experience less fever and less severe episodes after surgery compared to those receiving no surgery. The risk ratio (RR) for immediate resolution of symptoms after surgery that persisted until the end of follow-up was 4.38 (95% confidence interval (CI) 0.64 to 30.11); number needed to treat to benefit (NNTB) = 2, calculated based on an estimate that 156 in 1000 untreated children have a resolution) (moderate-certainty evidence). Both trials reported that there were no complications of surgery. However, the numbers of patients randomly allocated to surgery (19 and 14 patients respectively) were too small to detect potentially important complications such as haemorrhage. Surgery probably results in a large overall reduction in the average number of episodes over the total length of follow-up (rate ratio 0.08, 95% CI 0.05 to 0.13), reducing the average frequency of PFAPA episodes from one every two months to slightly less than one every two years (moderate-certainty evidence). Surgery also likely reduces severity, as indicated by the length of PFAPA symptoms during these episodes. One study reported that the average number of days per PFAPA episode was 1.7 days after receiving surgery, compared to 3.5 days in the control group (moderate-certainty evidence). The evidence suggests that the proportion of patients requiring corticosteroids was also lower in the surgery group compared to those receiving no surgery (RR 0.58, 95% CI 0.37 to 0.92) (low-certainty evidence). Other outcomes such as absence from school and quality of life were not measured or reported. Authors' conclusions The evidence for the effectiveness of tonsillectomy in children with PFAPA syndrome is derived from two small randomised controlled trials. These trials reported significant beneficial effects of surgery compared to no surgery on immediate and complete symptom resolution (NNTB = 2) and a substantial reduction in the frequency and severity (length of episode) of any further symptoms experienced. However, the evidence is of moderate certainty (further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate) due to the relatively small sample sizes of the studies and some concerns about the applicability of the results. Therefore, the parents and carers of children with PFAPA syndrome must weigh the risks and consequences of surgery against the alternative of using medications. It is well established that children with PFAPA syndrome recover spontaneously and medication can be administered to try and reduce the severity of individual episodes. It is uncertain whether adenoidectomy combined with tonsillectomy adds any additional benefit to tonsillectomy alone.

The incidence of mild and severe hypoglycaemia in patients with type 2 diabetes mellitus treated with sulfonylureas: a systematic review and meta-analysis.

Abstract: Patients with type 2 diabetes mellitus using sulfonylurea derivatives or insulin may experience hypoglycaemia. However, recent data regarding the incidence of hypoglycaemia are scarce. We conducted a systematic review and meta-analysis to determine the proportion of patients with type 2 diabetes mellitus that experience hypoglycaemia when treated with sulfonylurea or insulin. We searched MEDLINE and EMBASE for randomized controlled trials that compared incretin-based drugs to sulfonylureas or insulin and assessed hypoglycaemia incidence in the latter therapies. Subgroup and meta-regression analyses were performed to study possible associations with potential risk factors for hypoglycaemia. Data of 25 studies were extracted, 22 for sulfonylurea and 3 for insulin. Hypoglycaemia with glucose ≤3.1 mmol/L or ≤2.8 mmol/L was experienced by 10.1% [95% confidence interval (CI) 7.3-13.8%] and 5.9% (95% CI 2.5-13.4%) of patients with any sulfonylurea treatment. Severe hypoglycaemia was experienced by 0.8% (95% CI 0.5-1.3%) of patients. Hypoglycaemia with glucose ≤3.1 mmol/L and severe hypoglycaemia occurred least frequently with gliclazide: in 1.4% (95% CI 0.8-2.4%) and 0.1% (95% CI 0-0.7%) of patients, respectively. None of the risk factors were significant in a stepwise multivariate meta-regression analysis. Too few studies had insulin as comparator, so these data could not be meta-analysed. The majority of patients with type 2 diabetes mellitus on sulfonylurea therapy in clinical trials remain free of any relevant hypoglycaemia. Gliclazide was associated with the lowest risk of hypoglycaemia. Because participants in randomized controlled trials differ from the general population, care should be taken when translating these data into clinical practice.

Zanamivir for influenza in adults and children

Abstract: Objectives To describe the potential benefits and harms of zanamivir. Design Systematic review of clinical study reports of randomised placebo controlled trials and regulatory information Data sources Clinical study reports, trial registries, electronic databases, regulatory archives, and correspondence with manufacturers. Eligibility criteria for selecting studies Randomised placebo controlled trials in adults and children who had confirmed or suspected exposure to natural influenza. Main outcome measures Time to first alleviation of symptoms, influenza outcomes and complications, admissions to hospital, and adverse events in the intention to treat (ITT) population. Results We included 28 trials in stage 1 (judgment of appropriate study design) and 26 in stage 2 (formal analysis). For treatment of adults, zanamivir reduced the time to first alleviation of symptoms of influenza-like illness by 0.60 days (95% confidence interval 0.39 to 0.81, P<0.001, I2=9%), which equates to an average 14.4 hours’ reduction, or a 10% reduction in mean duration of symptoms from 6.6 days to 6.0 days. Time to first alleviation of symptoms was shorter in all participants when any relief drugs were allowed compared with no use. Zanamivir did not reduce the risk of self reported investigator mediated pneumonia (risk difference 0.17%, −0.73% to 0.70%) or radiologically confirmed pneumonia (−0.06%, −6.56% to 2.11%) in adults. The effect on pneumonia in children was also not significant (0.56%, −1.64% to 1.04%). There was no significant effect on otitis media or sinusitis in both adults and children, with only a small effect noted for bronchitis in adults (1.80%, 0.65% to 2.80%), but not in children. There were no data to assess effects on admissions in adults and children. Zanamivir tended to be well tolerated. In zanamivir prophylaxis studies, symptomatic influenza in individuals was significantly reduced (1.98%, (0.98% to 2.54%); reducing event rates from 3.26% to 1.27%, which means 51 people need to be treated to prevent one influenza case (95% confidence interval, 40 to 103). In contrast, the prophylaxis effect on asymptomatic influenza cases was not significant in individuals (risk difference 0.14%, −1.10% to 1.10%) or in households (1.32%, −2.20% to 3.84%). In households treated prophylactically there was an effect on symptomatic influenza (14.84%, 12.18% to 16.55%), but this was based on only two small studies including 824 participants. Prophylaxis in adults reduced unverified pneumonia (0.32%, 0.09% to 0.41%; NNTB (number needed to treat to benefit) 311, 244 to 1086) but had no effect on pneumonia in children or on bronchitis or sinusitis in adults or children (risk difference 0.32%, 0.09% to 0.41%; NNTB 311, 244 to 1086). Conclusions Based on a full assessment of all trials conducted, zanamivir reduces the time to symptomatic improvement in adults (but not in children) with influenza-like illness by just over half a day, although this effect might be attenuated by symptom relief medication. Zanamivir also reduces the proportion of patients with laboratory confirmed symptomatic influenza. We found no evidence that zanamivir reduces the risk of complications of influenza, particularly pneumonia, or the risk of hospital admission or death. Its harmful effects were minor (except for bronchospasm), perhaps because of low bioavailability.

The validity of recommendations from clinical guidelines: a survival analysis

Abstract: Background: Clinical guidelines should be updated to maintain their validity. Our aim was to estimate the length of time before recommendations become outdated. Methods: We used a retrospective cohort design and included recommendations from clinical guidelines developed in the Spanish National Health System clinical guideline program since 2008. We performed a descriptive analysis of references, recommendations and resources used, and a survival analysis of recommendations using the Kaplan–Meier method. Results: We included 113 recommendations from 4 clinical guidelines with a median of 4 years since the most recent search (range 3.9–4.4 yr). We retrieved 39 136 references (range 3343–14 787) using an exhaustive literature search, 668 of which were related to the recommendations in our sample. We identified 69 (10.3%) key references, corresponding to 25 (22.1%) recommendations that required updating. Ninety-two percent (95% confidence interval 86.9–97.0) of the recommendations were valid 1 year after their development. This probability decreased at 2 (85.7%), 3 (81.3%) and 4 years (77.8%). Interpretation: Recommendations quickly become outdated, with 1 out of 5 recommendations being out of date after 3 years. Waiting more than 3 years to review a guideline is potentially too long.

Surgical versus medical interventions for chronic rhinosinusitis with nasal polyps.

Abstract: Background Nasal polyps cause nasal obstruction, discharge and reduction in or loss of sense of smell, but their aetiology is unknown. The management of chronic rhinosinusitis with nasal polyps, aimed at improving these symptoms, includes both surgical and medical treatments, but there is no universally accepted management protocol. Objectives To assess the effectiveness of endonasal/endoscopic surgery versus medical treatment in chronic rhinosinusitis with nasal polyps. Search methods We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; CINAHL; Web of Science; Cambridge Scientific Abstracts; ICTRP and additional sources for published and unpublished trials. The date of the search was 20 February 2014. Selection criteria Randomised controlled trials of any surgical intervention (e.g. polypectomy, endoscopic sinus surgery) versus any medical treatment (e.g. intranasal and/or systemic steroids), including placebo, in adult patients with chronic rhinosinusitis with nasal polyps. Data collection and analysis We used the standard methodological procedures expected by The Cochrane Collaboration. Meta-analysis was not possible due to the heterogeneity of the studies and the selective (incomplete) outcome reporting by the studies. Main results Four studies (231 participants randomised) are included in the review. No studies were at low risk of bias. The studies compared different types of surgery versus various types and doses of systemic and topical steroids and antibiotics. There were three comparison pairs: (1) endoscopic sinus surgery (ESS) versus systemic steroids (one study, n = 109), (2) polypectomy versus systemic steroids (two studies, n = 87); (3) ESS plus topical steroid versus antibiotics plus high-dose topical steroid (one study, n = 35). All participants also received topical steroids but doses and types were the same between the treatment arms of each study, except for the study using antibiotics. In that study, the medical treatment arm had higher doses than the surgical arm. In two of the studies, the authors failed to report the outcomes of interest. Although there were important differences in the types of treatments and comparisons used in these studies, the results were similar. Primary outcomes: symptom scores and quality of life scores There were no important differences between groups in either the patient-reported disease-specific symptom scores or the health-related quality of life scores. Two studies (one comparing ESS plus topical steroid versus antibiotics plus high-dose topical steroid, the other ESS versus systemic steroids) failed to find a difference in generic health-related quality of life scores. The quality of this evidence is low or very low. Endoscopic scores and other secondary outcomes Two studies reported endoscopic scores. One study (ESS versus systemic steroids) reported a large, significant effect size in the surgical group, with a mean difference (MD) in score of -1.5 (95% confidence interval (CI) -1.78 to -1.22, n = 95) on a scale of 0 to 3 (0 = no polyposis, 3 = severe polyposis). In the other study (ESS plus topical steroid versus antibiotics plus high-dose topical steroid) no difference was found between the groups (MD 2.3%, 95% CI -17.4% to 12.8%, n = 34). None of the included studies reported recurrence rates. No differences were found for any objective measurements or olfactory tests in those studies in which they were measured. Complications Complication rates were not reported in all studies, but rates of up to 21% for medical treatment and 14.3% for surgical treatment are described. Epistaxis was the most commonly reported complication with both medical and surgical treatments, with severe complications reported rarely. Authors' conclusions The evidence relating to the effectiveness of different types of surgery versus medical treatment for adults with chronic rhinosinusitis with nasal polyps is of very low quality. The evidence does not show that one treatment is better than another in terms of patient-reported symptom scores and quality of life measurements. The one positive finding from amongst the several studies examining a number of different comparisons must be treated with appropriate caution, in particular when the clinical significance of the measure is uncertain. As the overall evidence is of very low quality (serious methodological limitations, reporting bias, indirectness and imprecision) and insufficient to draw firm conclusions, further research to investigate this problem, which has significant implications for quality of life and healthcare service usage, is justified.