Showing papers by "Cochrane Collaboration published in 2011"

Physical interventions to interrupt or reduce the spread of respiratory viruses.

Abstract: Background Viral epidemics or pandemics of acute respiratory infections like influenza or severe acute respiratory syndrome pose a global threat. Antiviral drugs and vaccinations may be insufficient to prevent their spread. Objectives To review the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. Search methods We searched The Cochrane Library, the Cochrane Central Register of Controlled Trials (CENTRAL 2010, Issue 3), which includes the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to October 2010), OLDMEDLINE (1950 to 1965), EMBASE (1990 to October 2010), CINAHL (1982 to October 2010), LILACS (2008 to October 2010), Indian MEDLARS (2008 to October 2010) and IMSEAR (2008 to October 2010). Selection criteria In this update, two review authors independently applied the inclusion criteria to all identified and retrieved articles and extracted data. We scanned 3775 titles, excluded 3560 and retrieved full papers of 215 studies, to include 66 papers of 67 studies. We included physical interventions (screening at entry ports, isolation, quarantine, social distancing, barriers, personal protection, hand hygiene) to prevent respiratory virus transmission. We included randomised controlled trials (RCTs), cohorts, case-controls, before-after and time series studies. Data collection and analysis We used a standardised form to assess trial eligibility. We assessed RCTs by randomisation method, allocation generation, concealment, blinding and follow up. We assessed non-RCTs for potential confounders and classified them as low, medium and high risk of bias. Main results We included 67 studies including randomised controlled trials and observational studies with a mixed risk of bias. A total number of participants is not included as the total would be made up of a heterogenous set of observations (participant people, observations on participants and countries (object of some studies)). The risk of bias for five RCTs and most cluster-RCTs was high. Observational studies were of mixed quality. Only case-control data were sufficiently homogeneous to allow meta-analysis. The highest quality cluster-RCTs suggest respiratory virus spread can be prevented by hygienic measures, such as handwashing, especially around younger children. Benefit from reduced transmission from children to household members is broadly supported also in other study designs where the potential for confounding is greater. Nine case-control studies suggested implementing transmission barriers, isolation and hygienic measures are effective at containing respiratory virus epidemics. Surgical masks or N95 respirators were the most consistent and comprehensive supportive measures. N95 respirators were non-inferior to simple surgical masks but more expensive, uncomfortable and irritating to skin. Adding virucidals or antiseptics to normal handwashing to decrease respiratory disease transmission remains uncertain. Global measures, such as screening at entry ports, led to a non-significant marginal delay in spread. There was limited evidence that social distancing was effective, especially if related to the risk of exposure. Authors' conclusions Simple and low-cost interventions would be useful for reducing transmission of epidemic respiratory viruses. Routine long-term implementation of some measures assessed might be difficult without the threat of an epidemic.

Thrombelastography (TEG) or thromboelastometry (ROTEM) to monitor haemotherapy versus usual care in patients with massive transfusion

Abstract: Background Severe bleeding and coagulopathy as a result of massive transfusion are serious clinical conditions that are associated with high mortality. Thromboelastography (TEG) and thromboelastometry (ROTEM) are increasingly used to guide transfusion strategy but their roles remain disputed. Objectives To systematically assess the benefits and harms of a TEG or ROTEM guided transfusion strategy in randomized trials involving patients with severe bleeding. Search methods Randomized clinical trials (RCTs) were identified from electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 9); MEDLINE; EMBASE; Science Citation Index Expanded; International Web of Science; CINAHL; LILACS; and the Chinese Biomedical Literature Database (up to 31st October 2010). We contacted trial authors, authors of previous reviews, and manufacturers in the field. Selection criteria We included all RCTs, irrespective of blinding or language, that compared transfusion guided by TEG or ROTEM to transfusion guided by clinical judgement and standard laboratory tests, or both. Data collection and analysis Two authors independently abstracted data; they resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as relative risks (RR) and on continuous outcomes as mean differences, with 95% confidence intervals (CI). Our primary outcome measure was all cause mortality. We performed subgroup and sensitivity analyses to assess the effect of TEG or ROTEM in adults and children on various clinical and physiological outcomes. We assessed the risk of bias through assessment of trial methodological components and the risk of random error through trial sequential analysis. Main results We included nine RCTs with a total of 776 participants; only one trial had a low risk of bias. We found two ongoing trials but were unable to retrieve any data from them. Compared with standard treatment, TEG or ROTEM showed no statistically significant effect on overall mortality (3.78% versus 5.11%, RR 0.77, 95% CI 0.35 to 1.72; I2 = 0%) but only five trials provided data on mortality. Our analyses demonstrated a statistically significant effect of TEG or ROTEM on the amount of bleeding (MD -85.05 ml, 95% CI -140.68 to -29.42; I2 = 26%) but failed to show any statistically significant effect on other predefined outcomes. Authors' conclusions There is an absence of evidence that TEG or ROTEM improves morbidity or mortality in patients with severe bleeding. Application of a TEG or ROTEM guided transfusion strategy seems to reduce the amount of bleeding but whether this has implications for the clinical condition of patients is still uncertain. More research is needed.

Classifications for Cesarean Section: A Systematic Review

Abstract: Competing Interests: Academic conflict of interest: Five authors of the present study have published a study on CS in Latin America using one of the classifications evaluated in the present systematic review. Betran AP, Gulmezoglu AM, Robson M, Merialdi M, Souza JP et al. (2009) WHO global survey on maternal and perinatal health in Latin America: classifying caesarean sections. Reprod Health 6: 18. Funding: The authors have no support or funding to report. The authors were personally salaried by their institutions during the period of writing, though no specific salary was set aside or given for the writing of this paper.

Exercise therapy for fibromyalgia.

Abstract: Fibromyalgia syndrome, a chronic condition typically characterized by widespread pain, nonrestorative sleep, fatigue, cognitive dysfunction, and other somatic symptoms, negatively impacts physical and emotional function and reduces quality of life. Exercise is commonly recommended in the management of people with fibromyalgia, and interest in examining exercise benefits for those with the syndrome has grown substantially over the past 25 years. Research supports aerobic and strength training to improve physical fitness and function, reduce fibromyalgia symptoms, and improve quality of life. However, other forms of exercise (e.g., tai chi, yoga, Nordic walking, vibration techniques) and lifestyle physical activity also have been investigated to determine their effects. This paper highlights findings from recent randomized controlled trials and reviews of exercise for people with fibromyalgia, and includes information regarding factors that influence response and adherence to exercise to assist clinicians with exercise and physical activity prescription decision-making to optimize health and well-being.

Gastro‐oesophageal reflux treatment for prolonged non‐specific cough in children and adults

Abstract: Background Gastroesophageal reflux disease (GORD) is said to be the causative factor in up to 41% of adults with chronic cough. However cough and GORD are common ailments and their co-existence by chance is high. Also cough can induce reflux episodes. Treatment for GORD includes conservative measures (diet manipulation), pharmaceutical therapy (motility or prokinetic agents, H2-antagonist and proton pump inhibitors (PPI)) and fundoplication. Objectives To evaluate the efficacy of GORD treatment on chronic cough in children and adults with GORD and prolonged cough that is not related to an underlying respiratory disease i.e. non-specific chronic cough. Search strategy We searched the Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE and EMBASE databases, review articles and reference lists of relevant articles. The date of last search was 24th April 2009. Selection criteria All randomised controlled trials (RCTs) on GORD treatment for cough in children and adults without primary lung disease. Data collection and analysis Two review authors independently assessed trial quality and extracted. Study authors were contacted for further information. Main results Eighteen studies (5 paediatric, 13 adults) were included. None of the paediatric studies could be included in meta-analysis. In adults, analysis on use of H2 antagonist, motility agents and conservative treatment for GORD were not possible (from lack of data) and there were no controlled studies on fundoplication as an intervention. Nine adult studies comparing PPI (two to three months) to placebo were analysed for various outcomes in themeta-analysis. Enrolment of participants subjects for two studies were primarily frommedical clinics and another eight studies were otolaryngology clinic patients or patients with laryngeal symptoms. Using “intention to treat”, pooled data from studies resulted in no significant difference between treatment and placebo in total resolution of cough, Odds Ratio 0.46 (95% confidence interval (CI) 0.19 to 1.15). Pooled data revealed no overall significant improvement in cough outcomes (end of trial or change in cough scores). Significant differences were only found in sensitivity analyses. A significant improvement in change of cough scores was found in end of intervention (two to three months) in those receiving PPI with a standardised mean difference of - 0.41 (95% CI -0.75 to -0.07) using generic inverse variance analysis on cross over trials. Two studies reported improvement in cough after five days to two weeks of treatment. Authors’ conclusions There is insufficient evidence to definitely conclude that GORD treatment with PPI is universally beneficial for cough associated with GORDin adults. The beneficial effect was only seen in sub-analysis. The optimal duration of such a trial of therapy to evaluate response could not be ascertained although two RCTs reported significant change by 2-weeks of therapy. Clinicians should be cognisant of a period (natural resolution with time) and placebo effect in studies that utilise cough as an outcome measure. Future paediatric and adult studies should be double blind, randomised controlled, parallel design, using treatments for at least two months, with validated subjective and objective cough outcomes and include ascertainment of time to respond as well as assessment of acid and/or non-acid reflux.

Gabapentin for acute and chronic pain

Abstract: Background February 2009: The authors are aware of unpublished trial data for Gabapentin which could affect the results of this review. This information together with that from trials published since 2005, will be considered when this review is updated in 2009. Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for chronic neuropathic pain, especially when the pain is lancinating or burning. Objectives To evaluate the analgesic effectiveness and adverse effects of gabapentin for pain management in clinical practice. Search strategy Randomised trials of gabapentin in acute, chronic or cancer pain were identified by MEDLINE (1966 to Nov 2004), EMBASE (1994 to Nov 2004), SIGLE (1980 to Jan 2004) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2004). Additional studies were identified from the reference list of the retrieved papers, and by contacting investigators. Date of most recent search: January 2004. Selection criteria Randomised trials reporting the analgesic effects of gabapentin in participants with subjective pain assessment as either the primary or a secondary outcome. Data collection and analysis Data were extracted by two independent review authors, and trials were quality scored. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse effects and drug-related study withdrawal. Main results Fourteen reports describing 15 studies of gabapentin were considered eligible (1468 participants). One was a study of acute pain. The remainder included the following conditions: post-herpetic neuralgia (two studies), diabetic neuropathy (seven studies), a cancer related neuropathic pain (one study) phantom limb pain (one study), Guillain Barre syndrome (one study), spinal chord injury pain (one study) and various neuropathic pains (one study). The study in acute post-operative pain (70 participants) showed no benefit for gabapentin compared to placebo for pain at rest. In chronic pain, the NNT for improvement in all trials with evaluable data is 4.3 (95% CI 3.5 to 5.7). Forty two percent of participants improved on gabapentin compared to 19% on placebo. The number needed to harm (NNH) for adverse events leading to withdrawal from a trial was not significant. Fourteen percent of participants withdrew from active arms compared to 10% in placebo arms. The NNH for minor harm was 3.7 (95% CI 2.4 to 5.4). The NNT for effective pain relief in diabetic neuropathy was 2.9 (95% CI 2.2 to 4.3) and for post herpetic neuralgia 3.9 (95% CI 3 to 5.7). Authors' conclusions There is evidence to show that gabapentin is effective in neuropathic pain. There is limited evidence to show that gabapentin is ineffective in acute pain.

Glucagon‐like peptide analogues for type 2 diabetes mellitus

Abstract: Background Glucagon-like peptide analogues are a new class of drugs used in the treatment of type 2 diabetes that mimic the endogenous hormone glucagon-like peptide 1 (GLP-1). GLP-1 is an incretin, a gastrointestinal hormone that is released into the circulation in response to ingested nutrients. GLP-1 regulates glucose levels by stimulating glucose-dependent insulin secretion and biosynthesis, and by suppressing glucagon secretion, delayed gastric emptying and promoting satiety. Objectives To assess the effects of glucagon-like peptide analogues in patients with type 2 diabetes mellitus. Search strategy Studies were obtained from electronic searches of The Cochrane Library (last search issue 1, 2011), MEDLINE (last search March 2011), EMBASE (last search March 2011), Web of Science (last search March 2011) and databases of ongoing trials. Selection criteria Studies were included if they were randomised controlled trials of a minimum duration of eight weeks comparing a GLP-1 analogue with placebo, insulin, an oral anti-diabetic agent, or another GLP-1 analogue in people with type 2 diabetes. Data collection and analysis Data extraction and quality assessment of studies were done by one reviewer and checked by a second. Data were analysed by type of GLP-1 agonist and comparison treatment. Where appropriate, data were summarised in a meta-analysis (mean differences and risk ratios summarised using a random-effects model). Main results Seventeen randomised controlled trials including relevant analyses for 6899 participants were included in the analysis. Studies were mostly of short duration, usually 26 weeks. In comparison with placebo, all GLP-1 agonists reduced glycosylated haemoglobin A1c (HbA1c) levels by about 1%. Exenatide 2 mg once weekly reduced HbA1c more than exenatide 10 mu g twice daily, sitagliptin and pioglitazone. Liraglutide 1.8 mg reduced HbA1c by 0.33% more than exenatide 10 mu g twice daily. Liraglutide led to similar improvements in HbA1c compared to sulphonylureas but reduced it more than sitagliptin and rosiglitazone. Both exenatide and liraglutide led to greater weight loss than most active comparators, including in participants not experiencing nausea. Hypoglycaemia occurred more frequently in participants taking concomitant sulphonylurea. GLP-1 agonists caused gastrointestinal adverse effects, mainly nausea. These adverse events were strongest at the beginning and then subsided. Beta-cell function was improved with GLP-1 agonists but the effect did not persist after cessation of treatment. None of the studies was long enough to assess long-term positive or negative effects. Authors' conclusions GLP-1 agonists are effective in improving glycaemic control.

Meta-analysis: antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding - an updated Cochrane review.

Abstract: Aliment Pharmacol Ther 2011; 34: 509–518 Summary Background Antibiotic prophylaxis seems to decrease the incidence of bacterial infections in patients with cirrhosis and upper gastrointestinal bleeding and is considered standard of care. However, there is no updated information regarding the effects of this intervention. Aim To assess the benefits and harms of antibiotic prophylaxis in cirrhotic patients with gastrointestinal bleeding by performing a systematic review of randomised trials. Methods We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE and Science Citation Index EXPANDED until June 2010. We statistically combined data calculating relative risk (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes. Results Twelve trials (1241 patients) evaluating antibiotic prophylaxis against placebo or no antibiotic prophylaxis were included. Antibiotic prophylaxis was associated with reduced mortality (RR 0.79, 95% CI 0.63–0.98), mortality from bacterial infections (RR 0.43, 95% CI 0.19–0.97), bacterial infections (RR 0.35, 95% CI 0.26–0.47), rebleeding (RR 0.53, 95% CI 0.38–0.74) and days of hospitalisation (MD −1.91, 95% CI −3.80–0.02). Trials analysing rebleeding rate and hospitalisation length are still scarce, thus, caution should be exerted when interpreting the results. Conclusions Antibiotic prophylaxis in patients with cirrhosis and upper gastrointestinal bleeding significantly reduced bacterial infections, and reduce all-cause mortality, bacterial infection mortality, rebleeding events and hospitalisation length. Novel clinically significant outcomes were included in this meta-analysis. Some benefits are biased and the risks are not yet properly assessed, this encourages future research in this field.

Grading quality of evidence and strength of recommendations in clinical practice guidelines part 3 of 3. The GRADE approach to developing recommendations.

Abstract: This is the third and last article in the series about the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to grading the quality of evidence and the strength of recommendations in clinical practice guidelines and its application in the field of allergy. We describe the factors that influence the strength of recommendations about the use of diagnostic, preventive and therapeutic interventions: the balance of desirable and undesirable consequences, the quality of a body of evidence related to a decision, patients' values and preferences, and considerations of resource use. We provide examples from two recently developed guidelines in the field of allergy that applied the GRADE approach. The main advantages of this approach are the focus on patient important outcomes, explicit consideration of patients' values and preferences, the systematic approach to collecting the evidence, the clear separation of the concepts of quality of evidence and strength of recommendations, and transparent reporting of the decision process. The focus on transparency facilitates understanding and implementation and should empower patients, clinicians and other health care professionals to make informed choices.

Dendritic cell based tumor vaccination in prostate and renal cell cancer: a systematic review and meta-analysis.

Abstract: Background More than 200 clinical trials have been performed using dendritic cells (DC) as cellular adjuvants in cancer. Yet the key question whether there is a link between immune and clinical response remains unanswered. Prostate and renal cell cancer (RCC) have been extensively studied for DC-based immunotherapeutic interventions and were therefore chosen to address the above question by means of a systematic review and meta-analysis.

The effectiveness of strategies to change organisational culture to improve healthcare performance: a systematic review

Abstract: Organisational culture is an anthropological metaphor used to inform research and consultancy and to explain organisational environments. In recent years, increasing emphasis has been placed on the need to change organisational culture in order to improve healthcare performance. However, the precise function of organisational culture in healthcare policy often remains underspecified and the desirability and feasibility of strategies to be adopted have been called into question. The objective of this review was to determine the effectiveness of strategies to change organisational culture in order to improve healthcare performance. We searched the following electronic databases: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Sociological Abstracts, Web of Knowledge, PsycINFO, Business and Management, EThOS, Index to Theses, Intute, HMIC, SIGLE, and Scopus until October 2009. The Database of Abstracts of Reviews of Effectiveness (DARE) was searched for related reviews. We also searched the reference lists of all papers and relevant reviews identified, and we contacted experts in the field for advice on further potential studies. We considered randomised controlled trials (RCTs) or well designed quasi-experimental studies (controlled clinical trials (CCTs), controlled before and after studies (CBAs), and interrupted time series (ITS) analyses). Studies could be set in any type of healthcare organisation in which strategies to change organisational culture in order to improve healthcare performance were applied. Our main outcomes were objective measures of professional performance and patient outcome. The search strategy yielded 4,239 records. After the full text assessment, two CBA studies were included in the review. They both assessed the impact of interventions aimed at changing organisational culture, but one evaluated the impact on work-related and personal outcomes while the other measured clinical outcomes. Both were at high risk of bias. Both reported positive results. Current available evidence does not identify any effective, generalisable strategies to change organisational culture. Healthcare organisations considering implementing interventions aimed at changing culture should seriously consider conducting an evaluation (using a robust design, e.g., ITS) to strengthen the evidence about this topic.

Neuraminidase inhibitors for preventing and treating influenza in healthy adults

Abstract: 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.

Efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder: a meta-regression analysis.

Abstract: Background: The efficacy of methylphenidate for adults with attention-deficit hyperactivity disorder (ADHD) shows wide between-study variability, which yields heterogeneous results in meta-analysis. The reasons for this variability have not been comprehensively investigated. Objectives: To determine the influence of treatment-related covariates of methylphenidate for adults with ADHD by means of meta-analysis. Clinical and methodological moderators and clinical trial reporting quality were also collected to control for their potential confounding effect. Methods: We searched for randomized, placebo-controlled clinical trials investigating the efficacy of methylphenidate for adults with ADHD. The study outcome was the efficacy of methylphenidate for reducing ADHD symptom severity. Treatment-related covariates included dose, type of drug-release formulation (formulations with a continuous drug release vs those with a non-continuous drug release), dose regimen (fixed vs flexible) and treatment length. Clinical (presence of co-morbid substance use disorders [SUD]) and methodological (design and rater) covariates were also collected, in addition to clinical trial reporting quality. The standardized mean difference (SMD) was calculated for each study. The analysis of the influence of methylphenidate effect modifiers was performed by means of random-effects meta-regression. Results: Eighteen studies were included. Dose, type of formulation and SUD appeared to modify the efficacy of methylphenidate in the bivariate analysis. These variables were included in a multivariate meta-regression, which showed that methylphenidate, at an average dose of 57.4 mg/day, delivered by means of non-continuous-release formulations, had a moderate effect on ADHD symptoms compared with placebo (SMD 0.57–0.58). A dose-response relationship was found, indicating that efficacy could be increased by SMD 0.11–0.12 for every 10 mg increment of methylphenidate. Continuous-release formulations and co-morbid SUD appeared to reduce the efficacy of methylphenidate. Nevertheless, the effect of treatment formulation may have been confounded by co-morbid SUD, since all studies using this continuous-release formulation were conducted in dual ADHD-SUD patients. No residual heterogeneity was found. Conclusions: This study shows that methylphenidate improves ADHD symptoms in adults in a dose-dependent fashion. The efficacy of methylphenidate appears to be reduced in patients with co-morbid SUD. It is unclear whether methylphenidate efficacy is influenced by the type of formulation, because the effect of this covariate is confounded by that of co-morbid SUD.

Single dose oral analgesics for acute postoperative pain in adults

Abstract: Background Thirty-five Cochrane Reviews of randomised trials testing the analgesic efficacy of individual drug interventions in acute postoperative pain have been published. This overview brings together the results of all those reviews and assesses the reliability of available data. Objectives To summarise data from all Cochrane Reviews that have assessed the effects of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery, who have been given a single dose of oral analgesic taken alone. Methods We identified systematic reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single Review Group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews we extracted the number needed to treat (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, the percentage of participants remedicating by 6, 8, 12, or 24 hours, and results for participants experiencing at least one adverse event. Main results The overview included 35 separate Cochrane Reviews with 38 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 45,000 participants studied in approximately 350 individual studies. The individual reviews included only high-quality trials of standardised design and outcome reporting. The reviews used standardised methods and reporting for both efficacy and harm. Event rates with placebo were consistent in larger data sets. No statistical comparison was undertaken. There were reviews but no trial data were available for acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for dexibuprofen, dextropropoxyphene 130 mg, diflunisal 125 mg, etoricoxib 60 mg, fenbufen, and indometacin. Where there was adequate information for drug/dose combinations (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable. Reliable results were obtained for 46 drug/dose combinations in all painful postsurgical conditions; 45 in dental pain and 14 in other painful conditions. NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours in the same pain condition. Participants reporting at least one adverse event were few and generally no different between active drug and placebo, with a few exceptions, principally for aspirin and opioids. Drug/dose combinations with good (low) NNTs were ibuprofen 400 mg (2.5; 95% confidence interval (CI) 2.4 to 2.6), diclofenac 50 mg (2.7; 95% CI 2.4 to 3.0), etoricoxib 120 mg (1.9; 95% CI 1.7 to 2.1), codeine 60 mg + paracetamol 1000 mg (2.2; 95% CI 1.8 to 2.9), celecoxib 400 mg (2.5; 95% CI 2.2 to 2.9), and naproxen 500/550 mg (2.7; 95% CI 2.3 to 3.3). Long duration of action (≥ 8 hours) was found for etoricoxib 120 mg, diflunisal 500 mg, oxycodone 10 mg + paracetamol 650 mg, naproxen 500/550 mg, and celecoxib 400 mg. Not all participants had good pain relief and for many drug/dose combinations 50% or more did not achieve at last 50% maximum pain relief over four to six hours. Authors' conclusions There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.

The acute management of trauma hemorrhage: a systematic review of randomized controlled trials

Abstract: Worldwide, trauma is a leading cause of death and disability. Haemorrhage is responsible for up to 40% of trauma deaths. Recent strategies to improve mortality rates have focused on optimal methods of early hemorrhage control and correction of coagulopathy. We undertook a systematic review of randomized controlled trials (RCT) which evaluated trauma patients with hemorrhagic shock within the first 24 hours of injury and appraised how the interventions affected three outcomes: bleeding and/or transfusion requirements; correction of trauma induced coagulopathy and mortality. Comprehensive searches were performed of MEDLINE, EMBASE, CENTRAL (The Cochrane Library Issue 7, 2010), Current Controlled Trials, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) and the National Health Service Blood and Transplant Systematic Review Initiative (NHSBT SRI) RCT Handsearch Database. A total of 35 RCTs were identified which evaluated a wide range of clinical interventions in trauma hemorrhage. Many of the included studies were of low methodological quality and participant numbers were small. Bleeding outcomes were reported in 32 studies; 7 reported significantly reduced transfusion use following a variety of clinical interventions, but this was not accompanied by improved survival. Minimal information was found on traumatic coagulopathy across the identified RCTs. Overall survival was improved in only three RCTs: two small studies and a large study evaluating the use of tranexamic acid. Despite 35 RCTs there has been little improvement in outcomes over the last few decades. No clear correlation has been demonstrated between transfusion requirements and mortality. The global trauma community should consider a coordinated and strategic approach to conduct well designed studies with pragmatic endpoints.

Conceptual frameworks and empirical approaches used to assess the impact of health research: an overview of reviews

Abstract: How to assess the impact of research is of growing interest to funders, policy makers and researchers mainly to understand the value of investments and to increase accountability. Broadly speaking the term "research impact" refers to the contribution of research activities to achieve desired societal outcomes. The aim of this overview is to identify the most common approaches to research impact assessment, categories of impact and their respective indicators. We systematically searched the relevant literature (PubMed, The Cochrane Library (1990-2009)) and funding agency websites. We included systematic reviews, theoretical and methodological papers, and empirical case-studies on how to evaluate research impact. We qualitatively summarised the included reports, as well the conceptual frameworks. We identified twenty-two reports belonging to four systematic reviews and 14 primary studies. These publications reported several theoretical frameworks and methodological approaches (bibliometrics, econometrics, ad hoc case studies). The "payback model" emerged as the most frequently used. Five broad categories of impact were identified: a) advancing knowledge, b) capacity building, c) informing decision-making, d) health benefits, e) broad socio-economic benefits. For each proposed category of impact we summarized a set of indicators whose pros and cons are presented and briefly discussed. This overview is a comprehensive, yet descriptive, contribution to summarize the conceptual framework and taxonomy of an heterogeneous and evolving area of research. A shared and comprehensive conceptual framework does not seem to be available yet and its single components (epidemiologic, economic, and social) are often valued differently in different models.

Diagnostic tests for autism spectrum disorder (ASD) in preschool children

Abstract: Background Autism spectrum disorder (ASD) is a behaviourally diagnosed condition. It is defined by impairments in social communication or the presence of restricted or repetitive behaviours, or both. Diagnosis is made according to existing classification systems. In recent years, especially following publication of the Diagnostic and Statistical Manual of Mental Disorders ‐ Fifth Edition (DSM‐5; APA 2013), children are given the diagnosis of ASD, rather than subclassifications of the spectrum such as autistic disorder, Asperger syndrome, or pervasive developmental disorder ‐ not otherwise specified. Tests to diagnose ASD have been developed using parent or carer interview, child observation, or a combination of both.

Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children ‐ a review of clinical study reports

Abstract: OBJECTIVES Influenza is an acute respiratory infection associated with raised temperature, headache, muscle ache and cough. The objective of this review was to assess the effects of neuraminidase inhibitors (NIs) in preventing cases of influenza and shortening or reducing the severity of influenza in healthy adults. A further objective was to estimate the frequency of adverse effects associated with NI administration. SEARCH STRATEGY We searched Medline, the Cochrane Acute Respiratory Infections Group trials register, the Cochrane Controlled Trials Register (CCTR), manufacturers' databases, Embase (1991 to 1998) and reference lists of articles in May 1999. We also contacted manufacturers, researchers in the field, and authors of studies evaluated in the review. SELECTION CRITERIA Randomised or quasi-randomised placebo-controlled studies of NIs in healthy adults. Studies assessing protection or treatment from exposure to naturally occurring and experimental influenza were considered. The main outcomes were numbers and/or severity of influenza cases and the number and seriousness of adverse effects. DATA COLLECTION AND ANALYSIS Two reviewers applied the inclusion criteria to the retrieved studies, assessed trial quality and extracted data. MAIN RESULTS Eight trials with 1180 adults were included. Overall the methodological quality of the studies appeared to be good. As a preventive measure, NIs when compared to placebo were 74% effective (95% confidence interval 50% to 87%) in preventing naturally occurring cases of clinically defined influenza, and 60% effective (95% confidence interval 76% to 33%) in preventing cases of laboratory confirmed influenza. As a treatment, NIs shorten the duration of symptoms by one day - weighted mean difference 1 (95% confidence interval -1.3 to -0.6). The time gained in returning to normal activities is half a day - weighted mean difference -0.5 ( 95% confidence interval -1.1 to -0.1) for laboratory cases of influenza. The adverse event profile (local nasal irritation) of Zanamivir appears no better than placebo - odds ratio 1.19 ( 95% confidence interval 0.39 to 3.62). Compared with rimantadine in a preventive role, Oseltamivir has a significantly lower incidence of adverse effects and significantly higher incidence of nausea. For treatment, the adverse event profile shows that gastrointestinal symptoms are significantly worse in NIs than placebo - Peto odds ratio 2.32 ( 95% confidence interval 1.55 to 3.47). REVIEWER'S CONCLUSIONS NIs are effective for the prevention and treatment of influenza. Overall NIs are safe, although Oseltamivir causes significant nausea.

Laser and intense pulsed light therapy for the treatment of hypertrophic scars: a systematic review

Abstract: Hypertrophic scars are difficult to improve and remain a therapeutic challenge. Several lasers and light sources have been evaluated in the past decades and have been shown to improve hypertrophic scars. However, a systematic review is not available. To assess current evidence of efficacy of all laser and intense pulsed light therapies used in the treatment of hypertrophic scars, we performed a systematic review searching electronic databases MEDLINE, EMBASE and CENTRAL. The quality of the controlled clinical trials was evaluated according to the Cochrane Collaboration's tool for assessing risk of bias. Thirteen articles involving seven different lasers met the inclusion criteria. Most evidence was found for the pulsed dye laser (PDL) 585 nm (eight studies), followed by the PDL 595 nm (two studies), whereas limited evidence (one trial per laser) was available for the fractional nonablative laser 1540 nm, CO₂ laser 10,600 nm, low-level laser therapy, Nd:YAG laser 532 nm and Erbium:YAG laser 2940 nm. Treatment recommendations should be formulated with caution as current evidence is insufficient for comparing the efficacy of different laser therapies. The PDL 585 nm showed a low efficacy for the treatment of hypertrophic scars. With moderate efficacy, the PDL 595 nm is promising, although more research is necessary. Little evidence was found for the efficacy of other lasers. Future research, with a low risk of bias, well-defined scar characteristics, validated outcome measures, standardized measurement methods, follow-up periods of at least 6 months and well-defined laser settings, is needed.

The international EQUATOR network: enhancing the quality and transparency of health care research

Abstract: CONSORT guidelines (Consolidated Standards for Reporting Trials) !" #$ % $ !" #$ !" #$ & ' trials (http://www.consort-statement.org/aboutconsort). The third and latest version of the core CONSORT *+ +% development from the CONSORT group is the EQUATOR / 01 2 $ Health Research) (http://www.equator-network. org/) . As the EQUATOR group states:” The EQUATOR ! / 3 4 & 5 developers of reporting guidelines, research funding

WHO Calls for Targeted Research on the Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses

Abstract: The WHO has undertaken an update of the 1998 WHO Cancer Pain Relief and Palliative Care in Children Guidelines, in extending the scope to persisting pain associated with other medical conditions. The new WHO Guidelines for Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses, using the GRADE approach for evidence synthesis and grading of recommendations, are expected to help reduce the enormous treatment gap for pain in children. The WHO aims to update these guidelines within the next five years. Given the paucity of studies in the paediatric population with persisting pain, a meaningful revision of these guidelines will need the international scientific community to invest in research on the topics that were identified as evidence gaps during the development process For this reason, the WHO calls for a collaborative effort to cover the identified priority research areas and related systematic reviews of evidence. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration

Systematic reviews and meta-analyses of preclinical studies: publication bias in laboratory animal experiments.

Abstract: In 2006, Peters et al. identified 86 systematic reviews (SRs) of laboratory animal experiments (LAEs). They found 46 LAE meta-analyses (MAs), often of poor quality. Six of these 46 MAs tried to assess publication bias. Publication bias is the phenomenon of an experiment's results determining its likelihood of publication, often over-representing positive findings. As such, publication bias is the Achilles heel of any SR. Since researchers increasingly become aware of the fact that SRs directly support the 'three Rs', we expect the number of SRs of LAEs will sharply increase. Therefore, it is useful to see how publication bias is dealt with. Our objective was to identify all SRs and MAs of LAEs where the purpose was to inform human health published between July 2005 and 2010 with special attention to MAs' quality features and publication bias. We systematically searched Medline, Embase, Toxline and ScienceDirect from July 2005 to 2010, updating Peters' review. LAEs not directly informing human health or concerning fundamental biology were excluded. We found 2780 references of which 163 met the inclusion criteria: 158 SRs, of which 30 performed an MA, and five MAs without an SR. The number of SRs roughly doubled every three years since 1997. The number of MAs roughly doubled every five years since 1999. Compared with before July 2005, more MAs were preceded by SR and reported on (quality) features of included studies and heterogeneity. A statistically significant proportion of MAs considered publication bias (26/35) and tried to formally assess it (21/35).

Ethical issues in preparing and publishing systematic reviews

Abstract: The medical evidence base, or ‘literature’, forms the basis for clinical and policy decisions, so those who contribute to it have a responsibility to ensure that it is as accurate and unbiased as possible. Since publications are also used to judge the productivity of individuals and departments, and to select candidates for academic positions, it is important that those who did the work receive fair credit. Preparing a systematic review is a form of research, and should therefore be undertaken in a responsible manner to ensure integrity and avoid misconduct. This paper sets out practical and ethical issues to be considered when preparing and publishing a systematic review. It is written primarily for authors involved in The Cochrane Collaboration, but has broader relevance. Cochrane Review Groups, which are responsible for the quality of reviews that they publish, have highlighted concerns about unclear or inappropriate authorship, copying of material from other sources, and dual or duplicate publication. Various journals and editors’ organizations have produced publication guidelines and instructions for potential authors. One of the best known is the Uniform Requirements for Manuscripts Submitted to Biomedical Journals, produced by the International Committee of Medical Journal Editors (1). Guidance is also available in the Cochrane Handbook (2). However, many of the requirements and conventions are scattered, so it may be hard for researchers to get a complete picture of best practices. Another problem facing those preparing systematic reviews is that general guidance, designed mainly for preparing primary reports of research, may not be applicable or may not cover the special issues that arise with systematic reviews. This paper therefore aims to help review authors avoid ethical problems by providing an introduction and overview of good practice in preparing and publishing systematic reviews.

Head-mounted peripheral vision display systems and methods

Abstract: A head-mounted peripheral vision display and associated methods display information to a user without distraction. A plurality of light display elements are positioned within an area of peripheral vision of at least one eye of the user such that the information is imparted to the user without a need for repositioning or refocusing of the eye. The information may be determined from data received from one or more sensors and an illumination pattern is determined based upon the performance information. The light display elements are controlled to display the illumination pattern to the user.