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Eight studies met inclusion criteria. They were heterogeneous in terms of participants, study designs, and interventions. Five of eight studies had high risk of bias. In 3 RCTs (312 participants), classroom-based didactic and experiential programs increased short-term knowledge of suicide (SMD = 1.51, 95% CI 0.57 to 2.45; moderate quality evidence) and knowledge of suicide prevention (SMD = 0.72, 95% CI 0.36 to 1.07; moderate quality evidence). The effect on suicide prevention self-efficacy in one RCT (152 participants) was uncertain (SMD = 0.20, 95% CI -0.13 to 0.54; low quality evidence). One CBA analysed the effects of an institutional policy that restricted student access to laboratory cyanide and mandated professional assessment for suicidal students. The incidence of student suicide decreased significantly at one university with the policy relative to 11 control universities, 2.00 vs. 8.68 per 100,000 (Z = 5.90; P < 0.05). Four CBAs explored effects of training 'gatekeepers' to recognize and respond to warning signs of emotional crises and suicide risk in students they encountered. The magnitude of effect sizes varied between studies. Gatekeeper training enhanced short-term suicide knowledge in students, peer advisors residing in student accommodation, and faculty and staff, and suicide prevention self-efficacy among peer advisors. There was no evidence of an effect on participants' suicide-related attitudes or behaviors. One CBA found no evidence of effects of gatekeeper training of peer advisors on suicide-related knowledge, self-efficacy, or gatekeeper behaviors measured four to six months after intervention. We found insufficient evidence to support widespread implementation of any programs or policies for primary suicide prevention in post-secondary educational settings. As all evaluated interventions combined primary and secondary prevention components, we were unable to determine the independent effects of primary preventive interventions. Classroom instruction and gatekeeper training increased short-term suicide-related knowledge. We found no studies that tested the effects of classroom instruction on suicidal behavior or long-term outcomes. Limited evidence suggested minimal longer-term effects of gatekeeper training on suicide-related knowledge, while no evidence was found evaluating its effect on suicidal behavior. A policy-based suicide intervention reduced student suicide, but findings have not been replicated. Our findings are limited by the overall low quality of the evidence and the lack of studies from middle- and low-income countries. Rigorously designed studies should test the effects of preventive interventions on important health outcomes, including suicidal ideation and behavior, in varying post-secondary settings.

We identified eight studies that were eligible for this Cochrane Review. All studies had both primary and secondary prevention components. That is, they targeted students known to be suicidal as well as those not known to be suicidal. We separately analysed the effects of classroom instruction, institutional policies, and gatekeeper training programs. Gatekeeper training programs train people to recognize and respond to warning signs of emotional crises or suicide risk in students they encounter. The evidence is current to June 2011. Three studies, including 312 students, evaluated classroom instruction. Classroom instruction increases short-term knowledge of suicide and suicide prevention. It may slightly enhance short-term confidence in ability to prevent suicide. However, long-term effects have not been studied. Effects of classroom instruction on suicidal behavior have also not been studied. One study evaluated an institutional policy. The policy restricted access to laboratory cyanide and required professional assessment for students who threatened or attempted suicide. The policy significantly reduced student suicides. These findings have not been tested in other post-secondary institutions. Four studies, ranging from 53 to 146 participants, evaluated the effect of gatekeeper training programs. Gatekeeper training may lead to small-to-medium improvements in short-term suicide-related knowledge and confidence about being able to prevent suicide. We found no evidence that gatekeeper training improved short-term attitudes toward suicide or long-term knowledge or behaviors about suicide. The effect of gatekeeper training on suicide or suicidal behavior has not been evaluated. The quality of evidence for short-term knowledge of suicide and suicide prevention was moderate. For suicide prevention self-efficacy, the quality of evidence was low. The quality of evidence was reduced because results were not similar across studies and there were not enough data.

10.1002/14651858.CD009439.pub2

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cochrane-simplification-train-2201

Of 2313 participants without prior cerebral ischemia from five randomized trials, the mean age was 69 years. Participant features and study quality were similar between trials: the OAC in all five trials was warfarin. About half of participants (N = 1154) were randomized to adjusted-dose warfarin with mean achieved INRs ranging between 2.0 to 2.6. During 1.5 years mean follow up, warfarin was associated with large, highly statistically significant reductions in all strokes (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.26 to 0.59), ischemic stroke (OR 0.34, 95% CI 0.23 to 0.52), all disabling or fatal stroke (OR 0.47, 95% CI 0.28 to 0.80), death (OR 0.69, 95% CI 0.50 to 0.94) and the combined endpoint of all stroke, myocardial infarction or vascular death (OR 0.56, 95% CI 0.42 to 0.76). The observed rates of intracranial and extracranial hemorrhage were not significantly increased by OAC therapy, but the confidence intervals were wide. Treatment with adjusted-dose warfarin to achieved INRs of 2 to 3 reduces stroke, disabling or fatal stroke, and death for patients with non-valvular AF. The benefits were not substantially offset by increased bleeding among these participants in randomized clinical trials. Limitations include relatively short follow up and imprecise estimates of bleeding risks from the selected participants enrolled in the trials. For primary prevention of stroke in AF patients, about 25 strokes and about 12 disabling or fatal strokes would be prevented yearly for every 1000 atrial fibrillation patients given OACs.

Oral anticoagulants prevent stroke and death in people with atrial fibrillation. Atrial fibrillation is an irregularity of the heartbeat that leads to blood clots forming in the upper chambers of the heart (the atria). These clots can break free and travel through the blood stream to the brain and cause a stroke. Anticoagulant drugs, such as warfarin, slow blood clotting. The degree of inhibition of blood clotting during warfarin treatment is measured by a blood test called the international normalized ratio (INR). Dosages of warfarin that lead to INRs of 2.0 to 2.6 reduce death and stroke when given to patients with atrial fibrillation. Oral anticoagulants can cause bleeding into the brain and elsewhere. However, provided that there is careful control of dosage (requiring INR measurements at least monthly with warfarin), the risk of serious bleeding is low. The decision about whether or not to use oral anticoagulants in patients with atrial fibrillation is guided by a number of factors, including the individual's risk of stroke, which varies widely among patients with atrial fibrillation. Most people with atrial fibrillation should be considered for treatment with oral anticoagulants based on their risk of stroke, ability to tolerate anticoagulation without bleeding, and access to adequate anticoagulation monitoring.

10.1002/14651858.CD001927.pub2

cochrane-simplification-train-2202

cochrane-simplification-train-2202

We identified one new study for this update, resulting in six trials (561 patients) meeting the inclusion criteria. Five of the six trials reported on the main outcome, migraine frequency. Although five of the trials were generally of good methodological quality, all studies were either of unclear or high risk of bias with regards to sample size. Pooled analysis of the results was not possible due to the lack of common outcome measures and heterogeneity between studies in terms of participants, interventions and designs. The most recent trial added to this version of the review is rigorous and larger (n = 218), using a stable feverfew extract at a dose determined by a previous dose-finding trial. It reports that feverfew reduced migraine frequency by 1.9 attacks from 4.8 to 2.9 and placebo by 1.3 from to 4.8 to 3.5 per month, resulting in a difference in effect between feverfew and placebo of 0.6 attacks per month. For the secondary outcome measures intensity and duration of migraine attacks, incidence and severity of nausea and vomiting, and global assessment no statistically significant differences were reported. Results of previous trials are not convincing: three trials reporting positive effects of feverfew are all of small sample size (17 to 60 participants), while two rigorous trials (n = 50, 147) did not find significant differences between feverfew and placebo. Only mild and transient adverse events, most commonly gastrointestinal complaints and mouth ulcers, were reported in the included trials. Since the last version of this review, one larger rigorous study has been included, reporting a difference in effect between feverfew and placebo of 0.6 attacks per month. This adds some positive evidence to the mixed and inconclusive findings of the previous review. However, this constitutes low quality evidence, which needs to be confirmed in larger rigorous trials with stable feverfew extracts and clearly defined migraine populations before firm conclusions can be drawn. It appears from the data reviewed that feverfew is not associated with any major safety concerns.

For this update of a previous Cochrane review, we reviewed the available evidence up to January 2015 for or against feverfew in the prevention of migraine and found six studies including 561 participants. Generally the studies were heterogeneous and their results were mixed. The previous version of this review showed no clear benefit of feverfew compared with placebo. We added a new study, which is larger and was carried out to high standards, to this review. It showed that feverfew reduced migraine frequency by a little more than half a migraine (0.6) per month compared to placebo. There was no difference in how severe the pain was, or how long it lasted. These results come from a single study of moderate size, therefore they must be viewed with caution until they are confirmed in other rigorous studies. No major adverse effects were associated with feverfew in the included studies.

10.1002/14651858.CD002286.pub3

cochrane-simplification-train-2203

cochrane-simplification-train-2203

We identified two RCTs meeting our inclusion criteria. The two trials tested different comparisons. One RCT included 35 participants and compared PCV with 'eight drugs in one day' multidrug chemotherapy, which is a combination of drugs with different mechanisms of action. Median survival was 6 months for the PCV group and 6.5 months for the 'eight drugs in one day' group. Adverse event outcomes were not graded or quantified. Progression-free survival (PFS) and quality of life (QoL) were not described in the methods and were not an outcome of interest. The sample size in this study was small, which lead to insufficient statistical power to detect clinical differences. According to the GRADE approach we judged the quality of evidence to be low for survival outcome and very low for chemotherapy toxicity The second multi-institutional RCT included 447 participants and compared PCV with Temozolomide (TMZ). Participants were randomised into three arms to receive PCV, and two different regimens of TMZ in a 2:1:1 ratio at first recurrence. The trial reported a median overall survival of 6.7 months and 7.2 months for the PCV and TMZ group respectively. It reported a PFS of 3.6 months for the PCV group and 4.7 months for the TMZ group. There was no observed difference of effect on overall survival (hazard ratio (HR) 0.91, 95% CI 0.74 to 1.11; P = 0.35) or PFS (HR 0.89, 95% CI 0.73 to 1.08; P = 0.23) in participants receiving PCV or TMZ chemotherapy. The proportion of people with at least one grade 3 or 4 adverse event was not clinically important at 9.2% versus 12.2% in PCV and TMZ arms respectively. Mean QoL scores calculated at baseline, 12 weeks and 24 weeks was 51.9 versus 59.8 favouring TMZ (P = 0.04) which is statistically but not clinically significant and was less than the pre-defined 10 point change for moderate improvement. We judged the GRADE quality of evidence to be moderate for overall survival, PFS, and chemotherapy toxicity and low for QoL. Evidence is based on a single large trial analysis as the other trial was small, with inadequate power to detect survival difference. Chemotherapy-naive patients with HGG at first recurrence when treated with PCV or TMZ have similar survival and time-to-progression outcomes. Adverse events are similar and QoL scores are statistically but not clinically significant between TMZ and PCV. Further RCTs should be conducted with adequate power following CONSORT guidelines with emphasis on QoL outcomes.

In this review we found two randomised controlled trials which studied PCV in recurrent HGG patients. The comparator was Temozolomide (TMZ) in one and 'eight drugs in one day' multidrug chemotherapy in another. Results of the two trials were not combined because they compared PCV with different treatments. Conclusions should be drawn with caution as they are based on a single trial analysis as the other trial was too small and underpowered to detect significant difference. Adverse effects and QoL results are based on a single trial analysis. The proportion of participants experiencing severe adverse events with PCV was similar to TMZ. QoL scores were higher with TMZ but not clinically significant. We attributed moderate-grade quality of evidence for overall survival, progression-free survival, chemotherapy toxicity and low-grade evidence for QoL. Chemotherapy-naive patients with HGG at first recurrence when treated with PCV or TMZ have similar survival and time-to-progression outcomes. Adverse events are similar and QoL scores are statistically but not clinically important between TMZ and PCV. The results do not apply to our contemporary patients with recurrent HGG as most of them would receive chemotherapy after original diagnosis as standard care. Participants in this trial received only radiotherapy prior to recurrence. Molecular markers were not used in decision making, which is the standard of care now.

10.1002/14651858.CD011773.pub2

cochrane-simplification-train-2204

cochrane-simplification-train-2204

We included 28 trials (4438 participants) in the updated review. We considered most participants to be at low to moderate risk of death after surgery. We assessed two studies as having low risk of bias and 11 studies high risk of bias. Investigators reported no differences in risk of mortality within the first year after surgery between low-dose versus high-dose opioid-based general anaesthesia groups (OR 0.53, 95% CI 0.25 to 1.12; eight trials, 1994 participants, low level of evidence) and between a time-directed extubation protocol versus usual care (OR 0.80, 95% CI 0.45 to 1.45; 10 trials, 1802 participants, low level of evidence). Researchers noted no significant differences between low-dose and high-dose opioid-based anaesthesia groups in the following postoperative complications: myocardial infarction (RR 0.98, 95% CI 0.48 to 1.99; eight trials, 1683 participants, low level of evidence), stroke (RR 1.17, 95% CI 0.36 to 3.78; five trials, 562 participants, low level of evidence) and tracheal reintubation (RR 1.77, 95% CI 0.38 to 8.27; five trials, 594 participants, low level of evidence). Comparisons with usual care revealed no significant differences in the risk of postoperative complications associated with a time-directed extubation protocol: myocardial infarction (RR 0.59, 95% CI 0.27 to 1.31; eight trials, 1378 participants, low level of evidence), stroke (RR 0.85, 95% CI 0.33 to 2.16; 11 trials, 1646 participants, low level of evidence) and tracheal reintubation (RR 1.34, 95% CI 0.74 to 2.41; 12 trials, 1261 participants, low level of evidence). Although levels of heterogeneity were high, low-dose opioid anaesthesia was associated with reduced time to extubation (reduction of 4.3 to 10.5 hours, 14 trials, 2486 participants, low level of evidence) and length of stay in the intensive care unit (reduction of 0.4 to 7.0 hours, 12 trials, 1394 participants, low level of evidence). Use of a time-directed extubation protocol was associated with reduced time to extubation (reduction of 3.7 to 8.8 hours, 16 trials, 2024 participants, low level of evidence) and length of stay in the intensive care unit (reduction of 3.9 to 10.5 hours, 13 trials, 1888 participants, low level of evidence). However, these two fast-track care interventions were not associated with reduced total length of stay in the hospital (low level of evidence). Low-dose opioid-based general anaesthesia and time-directed extubation protocols for fast-track interventions have risks of mortality and major postoperative complications similar to those of conventional (not fast-track) care, and therefore appear to be safe for use in patients considered to be at low to moderate risk. These fast-track interventions reduced time to extubation and shortened length of stay in the intensive care unit but did not reduce length of stay in the hospital.

We found 28 relevant randomized controlled studies, conducted between 1994 and 2015. Most of the 4438 adults who participated in these studies were undergoing first-time elective coronary artery graft bypass or valve replacement surgery, or both. They were at low to moderate risk of death after surgery. Eighteen studies examined the use of low-dose opioid-based general anaesthesia. Sixteen studies assessed how effective the protocols were in guiding staff to remove the tube that provided breathing support within eight hours after surgery. We found no differences in risk of death in the first year after surgery (18 trials, 3796 participants) nor in complications after surgery such as the need to replace the tracheal tube after surgery (17 trials, 1855 participants) and occurrence of myocardial infarction (16 trials, 3061 participants) or stroke (16 trials, 2208 participants), when we examined both types of interventions. Occurrences of acute renal failure, major bleeding, sepsis and wound infection also were not different. We rated the quality of evidence as low for both mortality and postoperative complications. Tracheal tubes were removed from adults in the fast-track care group up to a half day earlier than for those in the conventional care group. The fast-track group spent less time in the intensive care unit, but length of time spent in the hospital was similar between groups. The quality of evidence was low because of study limitations and unexplained variation in study findings. Large trials were few, and only one trial was designed to study postoperative effects of myocardial infarction, stroke or death. Our results did not apply to ‘high-risk' patients who had multiple concurrent health problems or to settings in which a short-acting opioid (remifentanil) was used for general anaesthesia. Fast-track cardiac care is safe in patients considered to be at low to moderate risk of death after surgery.

10.1002/14651858.CD003587.pub3

cochrane-simplification-train-2205

cochrane-simplification-train-2205

Our review included six RCTs (representing a total of 278 adult lung transplant recipients) that assessed the use of T-cell antibody induction. Evaluation of the included studies found all to be at high risk of bias. We conducted comparisons of polyclonal or monoclonal T-cell antibody induction versus no induction (3 studies, 140 participants); polyclonal T-cell antibody versus no induction (3 studies, 125 participants); interleukin-2 receptor antagonists (IL-2RA) versus no induction (1 study, 25 participants); polyclonal T-cell antibody versus muromonab-CD3 (1 study, 64 participants); and polyclonal T-cell antibody versus IL-2RA (3 studies, 100 participants). Overall we found no significant differences among interventions in terms of mortality, acute rejection, adverse effects, infection, pneumonia, cytomegalovirus infection, bronchiolitis obliterans syndrome, post-transplantation lymphoproliferative disease, or cancer. We found a significant outcome difference in one study that compared antithymocyte globulin versus muromonab-CD3 relating to adverse events (25/34 (74%) versus 12/30 (40%); RR 1.84, 95% CI 1.13 to 2.98). This suggested that antithymocyte globulin increased occurrence of adverse events. However, trial sequential analysis found that the required information size had not been reached, and the cumulative Z-curve did not cross the trial sequential alpha-spending monitoring boundaries. None of the studies reported quality of life or kidney injury. Trial sequential analyses indicated that none of the meta-analyses achieved required information sizes and the cumulative Z-curves did not cross the trial sequential alpha-spending monitoring boundaries, nor reached the area of futility. No clear benefits or harms associated with the use of T-cell antibody induction compared with no induction, or when different types of T-cell antibodies were compared were identified in this review. Few studies were identified that investigated use of antibodies against T-cells for induction after lung transplantation, and numbers of participants and outcomes were also limited. Assessment of the included studies found that all were at high risk of methodological bias. Further RCTs are needed to perform robust assessment of the benefits and harms of T-cell antibody induction for lung transplant recipients. Future studies should be designed and conducted according to methodologies to reduce risks of systematic error (bias) and random error (play of chance).

We analysed six studies that investigated the use of several different types of antibody therapies in 278 adult patients following lung transplantation. Flaws in study designs were found that indicated the studies were at risk of overestimating benefits and underestimating harms. Our analysis compared several types of antibodies, but with one exception - that antithymocyte globulin seemed to increase some adverse events - we found no significant differences in lung survival or rejection for any of the treatments. There was some uncertainty about this effect because the study was too small to be sure that observed benefits would apply to a larger population. We found no significant differences among therapies in terms of infection, bronchiolitis obliterans syndrome, post-transplantation lymphoproliferative disease, or cancer. Few investigated the use of T-cell antibodies after lung transplantation, and these included small numbers of participants. These limitations meant that our findings did not necessarily indicate no differences existed among comparisons in our analysis. To overcome this problem, larger and more robust randomised studies that assess the benefits and harms of antibodies against T-cells for people following lung transplantation are needed.

10.1002/14651858.CD008927.pub2

cochrane-simplification-train-2206

cochrane-simplification-train-2206

One new study (185 participants) was identified by the updated search and included in the review. We included a total of three studies in this update. Two small studies, both with cross-over design, with 20 and 10 participants respectively, were eligible for inclusion in the original review. One study with 20 participants examined the addition of intrathecal ketamine to intrathecal morphine, compared with intrathecal morphine alone. The second study with 10 participants examined the addition of intravenous ketamine bolus in two different doses to ongoing morphine therapy, compared with placebo. Both of these studies reported reduction in pain intensity and reduction in morphine requirements when ketamine was added to opioid for refractory cancer pain. The new study identified by the updated search had a parallel group design and 185 participants. This placebo-controlled study examined rapid titration of subcutaneous ketamine to high dose (500 mg) in participants who were using different opioids. There were no differences between groups for patient-reported pain intensity. Pooling of the data from the three included trials was not appropriate because of clinical heterogeneity. The study examining intrathecal drug administration reported no adverse events related to ketamine. In the study using intravenous bolus administration, ketamine caused hallucinations in four of 10 participants. In the rapid dose escalation/high-dose subcutaneous ketamine study, there was almost twice the incidence of adverse events in the ketamine group, compared to the placebo group, with the most common adverse events being needle site irritation and cognitive disturbance. Two serious adverse events (bradyarrhythmia and cardiac arrest) thought to be related to ketamine were also reported in this trial. For all three studies there was an unclear risk of bias overall. Using GRADE, we judged the quality of the evidence to be very low due to study limitations and imprecision due to the small number of participants in all comparisons. Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids for the relief of refractory cancer pain. The evidence was of very low quality, meaning that it does not provide a reliable indication of the likely effect, and the likelihood that the effect will be substantially different is high. Rapid dose escalation of ketamine to high dose (500 mg) does not appear to have clinical benefit and may be associated with serious adverse events. More randomised controlled trials (RCTs) examining specific low-dose ketamine clinical regimens in current use are needed.

In December 2016 and January 2017, we searched for clinical trials on the addition of ketamine to morphine-like drugs for cancer pain. We found one new study, together with the two studies included in the original review. The three studies were very different, using different doses of ketamine, different routes of administration and different durations of treatment and it was not possible to combine the results of these studies. The two smallest studies reported that the addition of ketamine to morphine reduced pain intensity and morphine requirements. The third study which used high doses of ketamine reported no clinical benefit of adding ketamine to different opioids. Increased doses of ketamine in some participants caused side effects such as hallucinations. The study which examined high doses of ketamine reported two serious adverse events, which may have been related to ketamine. Although two out of three studies reported reduction in pain, this could be due to chance in such small studies. We rated the quality of the evidence using four levels: very low, low, moderate, or high. Very low-quality evidence means that we are very uncertain about the results. High-quality evidence means that we are very confident in the results. The evidence from the studies was of very low quality. There were problems with the design of some studies and there were not enough data to answer some parts of our review question.

10.1002/14651858.CD003351.pub3

cochrane-simplification-train-2207

cochrane-simplification-train-2207

Thirty-six studies (2838 participants) were included. Xanthine versus placebo (18 studies): The proportion of symptom free days was larger with xanthine compared with placebo (7.97% [95% CI 3.41, 12.53]). Rescue medication usage was lower with xanthine, with no significant difference in symptom scores or hospitalisations. FEV1, and PEF were better with xanthine. Xanthine was associated with non-specific side-effects. Data from behavioural scores were inconclusive. Xanthine versus ICS (four studies) : Exacerbations were less frequent with ICS, but no significant difference on lung function was observed. Individual studies reported significant improvements in symptom measures in favour of steroids, and one study reported a difference in growth rate in favour of xanthine. No difference was observed for study withdrawal or tremor. Xanthine was associated with more frequent headache and nausea. Xanthine versus regular SABA (10 studies): No significant difference in symptoms, rescue medication usage and spirometry. Individual studies reported improvement in PEF with beta-agonist. Beta-agonist treatment led to fewer hospitalisations and headaches. Xanthine was associated with less tremor. Xanthine versus SCG (six studies ): No significant difference in symptoms, exacerbations and rescue medication. Sodium cromoglycate was associated with fewer gastro-intestinal side-effects than xanthine. Xanthine versus KET (one study): No statistical tests of significance between xanthine and ketotifen were reported. : Xanthine + ICS versus placebo + same dose ICS (three studies) : Results were conflicting due to clinical/methodological differences, and could not be aggregated. Xanthine + ICS versus ICS + leukotriene (one study): Results from one trial One small parallel study did not measure the primary outcome of symptoms; differences between treatments in end of treatment values were not statistically significant. Xanthines as first-line preventer alleviate symptoms and reduce requirement for rescue medication in children with mild to moderate asthma. When compared with ICS they were less effective in preventing exacerbations. Xanthines had similar efficacy as single preventative agent compared with regular SABA and SCG. Evidence on AEs (adverse effects) was equivocal: there was evidence for increased AEs overall, but no evidence that any specific AE (including effects on behaviour and attention) occurred more frequently than with placebo. There is insufficient evidence from available studies to make firm conclusions about the effectiveness of xanthines as add-on preventative treatment to ICS, and there are no published paediatric studies comparing xanthines with alternatives in this role. Our data suggest that xanthines are only suitable as first-line preventative asthma therapy in children when ICS are not available. Pre-trial exposure to the agents assessed may have pre-disposed the trial populations to tolerate the drug, and may have threatened blinding. They may have a role as add-on therapy in more severe asthma not controlled by ICS, but further studies are needed to examine this, and to define the risk-benefit ratio compared with other agents.

This review of studies has established that there is evidence for useful effects of these drugs in terms of symptom relief and lung function, but also some evidence of side-effects. As a primary preventative therapy, whilst there is evidence that xanthines are effective, this review suggests that more effective alternative treatment options (inhaled steroids) are available. In children with more severe asthma, the role of xanthines as an add-on therapy has only been assessed in a small number of trials, which report mixed effects. More studies in this area would help to generate a more reliable overview of the effects of treatment in these children. Xanthines are an effective preventative treatment in childhood asthma, but less effective than inhaled steroids, and with a less favourable side-effect profile. There is insufficient evidence at present to assess their role as "add-on" preventer treatment versus newer alternatives. Some of the trials exposed the children they recruited to a pre-trial phase of xanthine in order to maintain effective dosing during the trial. This could have made the trial participants less representative of the general population by making them more inclined to tolerate the study drug. This exposure also may have meant that they could recognise what drug they were taking during the blinded phase of the study.

10.1002/14651858.CD002885.pub2

cochrane-simplification-train-2208

cochrane-simplification-train-2208

We included 10 studies (165 participants) that examined the short- and medium-term effect of music therapy interventions (one week to seven months) for children with ASD. Music therapy was superior to 'placebo' therapy or standard care with respect to the primary outcomes social interaction within the therapy context (SMD 1.06, 95% CI 0.02 to 2.10, 1 RCT, n = 10); generalised social interaction outside of the therapy context (SMD 0.71, 95% CI 0.18 to 1.25, 3 RCTs, n = 57, moderate quality evidence), non-verbal communicative skills within the therapy context (SMD 0.57, 95% CI 0.29 to 0.85, 3 RCTs, n = 30), verbal communicative skills (SMD 0.33, 95% CI 0.16 to 0.49, 6 RCTs, n = 139), initiating behaviour (SMD 0.73, 95% CI 0.36 to 1.11, 3 RCTs, n = 22, moderate quality evidence), and social-emotional reciprocity (SMD 2.28, 95% CI 0.73 to 3.83, 1 RCT, n = 10, low quality evidence). There was no statistically significant difference in non-verbal communicative skills outside of the therapy context (SMD 0.48, 95% CI -0.02 to 0.98, 3 RCTs, n = 57, low quality evidence). Music therapy was also superior to 'placebo' therapy or standard care in secondary outcome areas, including social adaptation (SMD 0.41, 95% CI 0.21 to 0.60, 4 RCTs, n = 26), joy (SMD 0.96, 95% CI 0.04 to 1.88, 1 RCT, n = 10), and quality of parent-child relationships (SMD 0.82, 95% CI 0.13 to 1.52, 2 RCTs, n = 33, moderate quality evidence). None of the included studies reported any adverse effects. The small sample sizes of the studies limit the methodological strength of these findings. The findings of this updated review provide evidence that music therapy may help children with ASD to improve their skills in primary outcome areas that constitute the core of the condition including social interaction, verbal communication, initiating behaviour, and social-emotional reciprocity. Music therapy may also help to enhance non-verbal communication skills within the therapy context. Furthermore, in secondary outcome areas, music therapy may contribute to increasing social adaptation skills in children with ASD and to promoting the quality of parent-child relationships. In contrast to the studies included in an earlier version of this review published in 2006, the new studies included in this update enhanced the applicability of findings to clinical practice. More research using larger samples and generalised outcome measures is needed to corroborate these findings and to examine whether the effects of music therapy are enduring. When applying the results of this review to practice, it is important to note that the application of music therapy requires specialised academic and clinical training.

We included 10 studies with a total number of 165 participants. The studies examined the short- and medium-term effect of music therapy interventions (one week to seven months) for children with ASD. Music therapy was superior to 'placebo' therapy or standard care with respect to social interaction, non-verbal and verbal communicative skills, initiating behaviour, and social-emotional reciprocity. Music therapy was also superior to 'placebo' therapy or standard care in the areas of social adaptation, joy, and the quality of parent-child relationships. None of the included studies reported any side effects caused by music therapy. The quality of the evidence was moderate for social interaction outside of the therapy context, initiating behaviour, social adaptation, and the quality of the parent-child relationship, and low for the other three main outcomes (nonverbal communicative skills outside of the therapy context, verbal communicative skills outside of the therapy context, and social-emotional reciprocity). Reasons for limited quality of the evidence were issues with study design and small number of patients who participated in the studies. Music therapy may help children with ASD to improve their skills in important areas such as social interaction and communication. Music therapy may also contribute to increasing social adaptation skills in children with ASD and to promoting the quality of parent-child relationships. Some of the included studies featured interventions that correspond well with treatment in clinical practice. More research with adequate design and using larger numbers of patients is needed. It is important to specifically examine how long the effects of music therapy last. The application of music therapy requires specialised academic and clinical training. This is important when applying the results of this review to practice.

10.1002/14651858.CD004381.pub3

cochrane-simplification-train-2209

cochrane-simplification-train-2209

We included one United Kingdom (UK) study in the review. In this randomised controlled trial, a total of 80 participants, with a mean age of 58 years, were treated for 12 months by a specialist nurse or doctor, then were crossed over to the other clinician for the next 12 months. Two participants died during the study period. Six participants failed to cross over to nurse-led care because of unstable bronchiectasis. Overall, the level of study completion was high. Data show no difference in the numbers of exacerbations requiring treatment with antibiotics (rate ratio 1.09, 95% confidence interval (CI) 0.91 to 1.30, 80 participants, moderate-certainty evidence). Investigators reported more hospital admissions in the nurse-led care group (rate ratio 1.52, 95% CI 1.04 to 2.23, 80 participants, moderate-certainty evidence) and did not report emergency department attendance. For secondary outcomes, participants in the nurse-led care group used more healthcare resources during the first year of the trial. Increased admissions and greater use of resources made treatment costs for nurse-led groups' higher. Total costs for both years of the study were £8,464 and £5,228 for nurse-led care compared with doctor-led care. However, by the second year, treatment costs were almost equitable between the two groups, which may reflect the nurses' learning of how to better treat people with bronchiectasis. No statistically significant changes were observed in quality of life, exercise capacity, mortality, or lung function. Wide confidence intervals led to uncertainty regarding these results. Adverse events were not an outcome for this review. This update of the review shows that only one trial met review criteria. Review authors were unable to demonstrate effectiveness of nurse-led care compared with doctor-led care on the basis of findings of a single study. The included study reported no significant differences, but limited evidence means that differences in clinical outcomes between nurse-led care and usual care within the setting of a specialist clinic remain unclear. Further research is required to determine whether nurse-led care is cost-effective, if guidelines and protocols for bronchiectasis management are followed does this increases costs and how effective nurse-led management of bronchiectasis is in other clinical settings such as inpatient and outreach.

We found one study from the United Kingdom involving 80 people with bronchiectasis. The study was completed in 2002, when management of bronchiectasis was different from today. Participants were divided into two groups: One group of outpatients was observed for a 12-month period under the care of the specialist nurse, and the other under care of the doctor. After 12 months, these participants swapped groups. We found no significant differences between nurse-led and doctor-led care in terms of lung function, infective flareups (exacerbations), or quality of life. In the first year of the study we noted increased costs for nurse-led care with more hospital admissions and greater use of antibiotic injections. The certainty of evidence in the one included study was satisfactory, given that the study design meant participants knew which group they belonged to. More research is required to determine how nurse specialists compare with doctors in providing safe and effective treatment for patients with stable bronchiectasis. This Cochrane plain language summary was up-to-date as of March 2018.

10.1002/14651858.CD004359.pub2

cochrane-simplification-train-2210

cochrane-simplification-train-2210

We included sixteen controlled trials involving 2318 adult participants. The studies measured diverse outcomes. Many of the participants found recordings or summaries of their consultations valuable, with between 60% and 100% of participants (across twelve studies) reading the summary or listening to the recording at least once. The recordings were used to help inform family and friends (range 41.5% to 94.4% of participants in nine studies). Five out of nine studies reported better recall of information for those receiving recordings or summaries. Three out of ten studies found that participants provided with a recording or summary were more satisfied. No studies (out of ten) found any statistically significant difference between groups in terms of anxiety or depression. Three studies evaluated the effects on quality of life, but found no main effects. No study evaluated the intervention's effects on survival. The provision of recordings or summaries of key consultations may benefit most adults with cancer. Although more research is needed to improve our understanding of these interventions, most patients find them very useful. Practitioners should consider offering people recordings or written summaries of their consultations

The review of trials examined the effects of giving people with cancer audio recordings or written summaries of consultations. Most people found them useful as a personal reminder, to inform their families or friends, or to play to their general practitioners. People tended to remember more of the information they were given, and some were more satisfied with the information they received. Recordings or summaries did not make people more anxious or depressed. The recordings had no effects on quality of life, and no studies measured survival.

10.1002/14651858.CD001539.pub2

cochrane-simplification-train-2211

cochrane-simplification-train-2211

We included 10 randomised trials (836 participants) in this review. Four trials (40%) had low risk of bias, the remaining 60% of trials had a high risk of bias. The quality of the evidence for the effects of CBT on patients with chronic NP was from very low to moderate. There was low quality evidence that CBT was better than no treatment for improving pain (standard mean difference (SMD) -0.58, 95% confidence interval (CI) -1.01 to -0.16), disability (SMD -0.61, 95% CI -1.21 to -0.01), and quality of life (SMD -0.93, 95% CI -1.54 to -0.31) at short-term follow-up, while there was from very low to low quality evidence of no effect on various psychological indicators at short-term follow-up. Both at short- and intermediate-term follow-up, CBT did not affect pain (SMD -0.06, 95% CI -0.33 to 0.21, low quality, at short-term follow-up; MD -0.89, 95% CI -2.73 to 0.94, low quality, at intermediate-term follow-up) or disability (SMD -0.10, 95% CI -0.40 to 0.20, moderate quality, at short-term follow-up; SMD -0.24, 95% CI-0.54 to 0.07, moderate quality, at intermediate-term follow-up) compared to other types of interventions. There was moderate quality evidence that CBT was better than other interventions for improving kinesiophobia at intermediate-term follow-up (SMD -0.39, 95% CI -0.69 to -0.08, I2 = 0%). Finally, there was very low quality evidence that CBT in addition to another intervention did not differ from the other intervention alone in terms of effect on pain (SMD -0.36, 95% CI -0.73 to 0.02) and disability (SMD -0.10, 95% CI -0.56 to 0.36) at short-term follow-up. For patients with subacute NP, there was low quality evidence that CBT was better than other interventions at reducing pain at short-term follow-up (SMD -0.24, 95% CI -0.48 to 0.00), while no difference was found in terms of effect on disability (SMD -0.12, 95% CI -0.36 to 0.12) and kinesiophobia. None of the included studies reported on adverse effects. With regard to chronic neck pain, CBT was found to be statistically significantly more effective for short-term pain reduction only when compared to no treatment, but these effects could not be considered clinically meaningful. When comparing both CBT to other types of interventions and CBT in addition to another intervention to the other intervention alone, no differences were found. For patients with subacute NP, CBT was significantly better than other types of interventions at reducing pain at short-term follow-up, while no difference was found for disability and kinesiophobia. Further research is recommended to investigate the long-term benefits and risks of CBT including for the different subgroups of subjects with NP.

We examined the research published up to November 2014. We included 10 randomised trials (836 participants). Two studies included subjects with subacute NP (337 participants), while the other eight studies included participants with chronic NP (499 participants). CBTwas compared to no treatment (225 participants) or to other types of treatments (506 participants), or combined with another intervention (e.g. physiotherapy) and compared to the other intervention alone (200 participants). The interventions were carried out at primary and secondary health care centres. With regard to chronic NP, CBT was statistically significantly better than no treatment at improving pain, disability, and quality of life, but these effects could not be considered clinically meaningful. No differences between CBT and other types of interventions (e.g. medication, education, physiotherapy, manual therapy, and exercises) were found in terms of pain and disability; there was moderate quality evidence that CBT was better than other interventions in improving fear of movement. Also, there was very low quality evidence that CBT added to another intervention was no better at improving pain and disability than the other intervention alone . For subacute NP, there was low quality evidence that CBT was statistically significantly better than other types of interventions (e.g. manual therapy or education) for improving pain, but this effect was not clinically relevant. No difference was found in terms of disability and fear of movement. None of the included studies reported on whether any adverse effects related to cognitive-behavioural therapy were observed. The quality of evidence in this review ranged between “very low” and “moderate”. Therefore, the review results should be interpreted with caution. More high quality randomised trials are needed to address short and long term benefits of cognitive-behavioural therapy in subacute and chronic neck pain, and its effectiveness compared with other treatments, and to better understand which patients may benefit most from this type of intervention.

10.1002/14651858.CD010664.pub2

cochrane-simplification-train-2212

cochrane-simplification-train-2212

We included 10 studies with 709 participants in this review. Of the 10 studies, eight were conducted in high income countries (USA and Italy), seven were conducted prior to 2000 and seven had predominantly men. Seven studies assessed antidepressants versus placebo, two compared different antidepressant classes and one had three arms comparing two antidepressant classes with placebo. Antidepressant therapy may result in a greater improvement in depression compared to placebo. There was a moderate improvement in depression when assessed with the Hamilton Depression Rating Scale (HAM-D) score as a continuous outcome (SMD 0.59, 95% CI 0.21 to 0.96; participants = 357; studies = 6; I2 = 62%, low quality evidence). However, there was no evidence of improvement when this was assessed with HAM-D score as a dichotomized outcome (RR 1.10, 95% CI 0.89 to 1.35; participants = 434; studies = 5; I2 = 0%, low quality evidence) or Clinical Global Impression of Improvement (CGI-I) score (RR 1.28, 95% CI 0.93 to 1.77; participants = 346; studies = 4; I2 = 29%, low quality evidence). There was little to no difference in the proportion of study dropouts between study arms (RR 1.28, 95% CI 0.91 to 1.80; participants = 306; studies = 4; I2 = 0%, moderate quality evidence). The methods of reporting adverse events varied substantially between studies, this resulted in very low quality evidence contributing to a pooled estimate (RR 0.88, 95% CI 0.64 to 1.21; participants = 167; studies = 2; I2 = 34%; very low quality evidence). Based on this, we were unable to determine if there was a difference in the proportion of participants experiencing adverse events in the antidepressant versus placebo arms. However, sexual dysfunction was reported commonly in people receiving selective serotonin reuptake inhibitors (SSRIs). People receiving tricyclic antidepressants (TCAs) frequently reported anticholinergic adverse effects such as dry mouth and constipation. There were no reported grade 3 or 4 adverse events in any study group. There was no evidence of a difference in follow-up CD4 count at study termination (MD -6.31 cells/mm3, 95% CI -72.76 to 60.14; participants = 176; studies = 3; I2 = 0%; low quality evidence). Only one study evaluated quality of life score (MD 3.60, 95% CI -0.38 to 7.58; participants = 87; studies = 1; very low quality evidence), due to the poor quality evidence we could not draw conclusions for this outcome. There were few studies comparing different antidepressant classes. We are uncertain if SSRIs differ from TCAs with regard to improvement in depression as evaluated by HAM-D score (MD -3.20, 95% CI -10.87 to 4.47; participants = 14; studies = 1; very low quality evidence). There was some evidence that mirtazapine resulted in a greater improvement in depression compared to an SSRI (MD 9.00, 95% CI 3.61 to 14.39; participants = 70; studies = 1; low quality evidence); however, this finding was not consistent for all measures of improvement in depression for this comparison. No studies reported on virological suppression or any other HIV specific outcomes. The studies included in this review had an overall unclear or high risk of bias due to under-reporting of study methods, high risk of attrition bias and inadequate sequence generation methods. Heterogeneity between studies and the limited number of participants, and events lead to downgrading of the quality of the evidence for several outcomes. This review demonstrates that antidepressant therapy may be more beneficial than placebo for the treatment of depression in PLWH. The low quality of the evidence contributing to this assessment and the lack of studies representing PLWH from generalized epidemics in low- to middle-income countries make the relevance of these finding in today's context limited. Future studies that evaluate the effectiveness of antidepressant therapy should be designed and conducted rigorously. Such studies should incorporate evaluation of stepped care models and health system strengthening interventions in the study design. In addition, outcomes related to HIV care and antiretroviral therapy should be reported.

Most studies were conducted more than a decade ago, in the USA, in predominantly men. We found that antidepressant therapy may improve depressive symptoms when compared to a placebo tablet. There was no clear evidence of a difference in the number of people who dropped out of care when comparing people who received antidepressants with people who received a placebo. We cannot be certain if one type of antidepressant works better than another. Side effects were very common among all study participants. Although there were no clear conclusions on which side effects were most common or if side effects occurred more frequently in people taking antidepressants compared to a placebo, participants receiving antidepressants called selective serotonin reuptake inhibitors did report sexual problems frequently. People receiving medicines called tricyclic antidepressants reported constipation and dry mouth frequently. No studies reported on how antidepressant therapy affected the effectiveness of antiretroviral therapy. The evidence used to generate several of the results was assessed as low or very low quality. The review authors recommend that new studies on treatment of depression should be conducted in countries and population groups where HIV is most common. These studies should evaluate what causes depression in these populations and how to best to incorporate antidepressant therapy with other strategies for the management of PLWH and depression.

10.1002/14651858.CD008525.pub3

cochrane-simplification-train-2213

cochrane-simplification-train-2213

We included 12 trials in the original review (2009) and included no further trials in the first update (2011). An additional seven new trials met the inclusion criteria in this second update. In total, we included 19 RCTs involving 1346 participants at entry, with 11 trials awaiting classification either because the full text was unavailable or information in the full text failed to clarify eligibility. We excluded most trials because TENS was given in combination with another treatment as part of the formal study design or TENS was not delivered using appropriate TENS technique. The types of acute pain included in this Cochrane Review were procedural pain, e.g. cervical laser treatment, venepuncture, screening flexible sigmoidoscopy and non-procedural pain, e.g. postpartum uterine contractions and rib fractures. We pooled data for pain intensity for six trials (seven comparisons) comparing TENS with placebo but the I2 statistic suggested substantial heterogeneity. Mean difference (MD) with 95% confidence intervals (CIs) on a visual analogue scale (VAS, 100 mm) was -24.62 mm (95% CI -31.79 to -17.46) in favour of TENS. Data for the proportion of participants achieving ≥ 50% reduction in pain was pooled for four trials (seven comparisons) and relative risk was 3.91 (95% CI 2.42 to 6.32) in favour of TENS over placebo. We pooled data for pain intensity from five trials (seven comparisons) but the I2 statistic suggested considerable heterogeneity. MD was -19.05 mm (95% CI -27.30 to -10.79) in favour of TENS using a random-effects model. It was not possible to pool other data. There was a high risk of bias associated with inadequate sample sizes in treatment arms and unsuccessful blinding of treatment interventions. Seven trials reported minor adverse effects, such as mild erythema and itching underneath the electrodes and participants disliking TENS sensation. This Cochrane Review update includes seven new trials, in addition to the 12 trials reviewed in the first update in 2011. The analysis provides tentative evidence that TENS reduces pain intensity over and above that seen with placebo (no current) TENS when administered as a stand-alone treatment for acute pain in adults. The high risk of bias associated with inadequate sample sizes in treatment arms and unsuccessful blinding of treatment interventions makes definitive conclusions impossible. There was incomplete reporting of treatment in many reports making replication of trials impossible.

We included 19 clinical trials published up to 3 December 2014, which examined 1346 people. The trials administered TENS to produce a strong non painful 'tingling' sensation at the site of acute pain. The trials assessed TENS for cervical laser treatment, venepuncture, sigmoidoscopy, rib fractures and uterine contractions after childbirth. We did not include trials that assessed TENS for pain associated with childbirth, dental procedures and menstruation because they have been the subject of other Cochrane Reviews. Eleven trials are awaiting classification. TENS was better than placebo TENS (delivering no electrical current) at reducing the intensity of acute pain but the reduction in pain was not consistent across all trials. This finding was based on an analysis of only six of the 19 trials. There was an insufficient number patients to make a firm conclusion. A small number of patients experienced itching and redness beneath the TENS pads or disliked the sensation produced by TENS. Overall we concluded that TENS may reduce the intensity of acute pain in some patients but the quality of evidence was weak. TENS is inexpensive, safe and can be self-administered. We recommended that TENS should be considered as a treatment option given on its own or in combination with other treatments. The quality of the evidence was moderate to low because sample sizes were small and some patients were aware that they were receiving TENS or placebo.

10.1002/14651858.CD006142.pub3

cochrane-simplification-train-2214

cochrane-simplification-train-2214

We included 18 RCTs involving 2952 participants; 15 compared rhCG with uhCG, and 3 compared rhLH with uhCG. The evidence for different comparisons ranged from very low to high quality: limitations were poor reporting of study methods and imprecision. Pharmaceutical companies funded 9 of the 18 studies, and 5 studies did not clearly report funding source. Ongoing pregnancy/live birth There was no conclusive evidence of a difference between rhCG and uhCG (OR 1.15, 95% CI 0.89 to 1.49; 7 RCTs, N = 1136, I2 = 0%, moderate quality evidence) or between rhLH and uhCG (OR 0.95, 95% CI 0.51 to 1.78, 2 RCTs, N = 289, I2 = 0%, very low quality evidence) for ongoing pregnancy/live birth rates. OHSS There was no evidence of a difference between rhCG and uhCG in the incidence of OHSS: moderate to severe OHSS (OR 1.76, 95% CI 0.37 to 8.45; 3 RCTs, N = 417, I2 = 0%, low quality evidence), moderate OHSS (OR 0.78, 95% CI 0.27 to 2.27; 1 RCT, N = 243, I2 = 0%, low quality evidence), mild to moderate OHSS (OR 1.00, 95% CI 0.42 to 2.38; 2 RCTs, N = 320, I2 = 0%, low quality evidence) or undefined OHSS (OR 1.18, 95% CI 0.50 to 2.78; 3 RCTs, N = 495, I2 = 0%, low quality evidence). Likewise, there was no evidence of a difference between rhLH and uhCG in OHSS rates for moderate OHSS (OR 0.82, 95% CI 0.39 to 1.69, 2 RCTs, N = 280, I2 = 5%, very low quality evidence). Other adverse events There was no evidence of a difference in miscarriage rates between rhCG and uhCG (OR 0.72, 95% CI 0.41 to 1.25; 8 RCTs, N = 1196, I2 = 0%, low quality evidence) or between rhLH and uhCG (OR 0.95, 95% CI 0.38 to 2.40; 2 RCTs, N = 289, I2 = 0%, very low quality evidence). For other adverse effects (most commonly injection-site reactions) rhCG was associated with a lower number of adverse events than uhCG (OR 0.52, 95% CI 0.35 to 0.76; 5 RCTS, N = 561; I2 = 67%, moderate quality evidence). However, when we used a random-effects model due to substantial statistical heterogeneity, there was no evidence of a difference between the groups (OR 0.56, 95% CI 0.27 to 1.13). Only one study comparing rLH and uhCG reported other adverse events, and it was impossible to draw conclusions. We conclude that there is no evidence of a difference between rhCG or rhLH and uhCG for live birth or ongoing pregnancy rates or rates of OHSS.

We found 18 studies in 2952 women undergoing IVF or ICSI. Fifteen trials in 2473 women compared rhCG with uhCG, and three trials in 479 women compared rLH with uhCG. Women in the studies were 18 to 45 years old, with regular menstrual cycles and no history of OHSS. Types of subfertility included tubal disease, endometriosis, unexplained infertility and male factor infertility. Pharmaceutical companies funded 9 of the 18 studies; 4 studies were free of commercial funding, and the remaining 5 studies did not clearly report a funding source. The evidence is current to April 2015. There was no evidence of a difference between rhCG and uhCG or between RhLH and uhCG in rates of live birth/ongoing pregnancy or OHSS. Studies did not report much evidence on adverse events other than OHSS, and the evidence they did report was inconclusive. For the comparison 'rhCG versus uhCG', the evidence was of moderate quality for ongoing pregnancy/live birth rate and of low quality for incidence of OHSS. The main limitation of the evidence was lack of precision (i.e. study size was too small to rule out the role of chance). For the comparison 'rLH versus uhCG', the evidence was of very low quality for both ongoing pregnancy/live birth rate and incidence of OHSS. The main limitations of the evidence were lack of precision and poor reporting of study methods.

10.1002/14651858.CD003719.pub4

cochrane-simplification-train-2215

cochrane-simplification-train-2215

We included 22 studies with 1097 randomised participants. Twenty-one studies with 890 participants contributed data to meta-analyses. Participants in the studies had dementia of varying degrees of severity, and all were resident in institutions. Seven studies delivered an individual music intervention; the other studies delivered the intervention to groups of participants. Most interventions involved both active and receptive musical elements. The methodological quality of the studies varied. All were at high risk of performance bias and some were at high risk of detection or other bias. At the end of treatment, we found low-quality evidence that the interventions may improve emotional well-being and quality of life (standardised mean difference (SMD) 0.32, 95% confidence interval (CI) 0.02 to 0.62; 9 studies, 348 participants) and reduce anxiety (SMD –0.43, 95% CI –0.72 to –0.14; 13 studies, 478 participants). We found low-quality evidence that music-based therapeutic interventions may have little or no effect on cognition (SMD 0.15, 95% CI –0.06 to 0.36; 7 studies, 350 participants). There was moderate-quality evidence that the interventions reduce depressive symptoms (SMD –0.27, 95% CI –0.45 to –0.09; 11 studies, 503 participants) and overall behaviour problems (SMD –0.23, 95% CI –0.46 to –0.01; 10 studies, 442 participants), but do not decrease agitation or aggression (SMD –0.07, 95% CI –0.24 to 0.10; 14 studies, 626 participants). The quality of the evidence on social behaviour was very low, so effects were very uncertain. The evidence for long-term outcomes measured four or more weeks after the end of treatment was of very low quality for anxiety and social behaviour, and for the other outcomes, it was of low quality for little or no effect (with small SMDs, between 0.03 and 0.34). Providing people with dementia who are in institutional care with at least five sessions of a music-based therapeutic intervention probably reduces depressive symptoms and improves overall behavioural problems at the end of treatment. It may also improve emotional well-being and quality of life and reduce anxiety, but may have little or no effect on agitation or aggression or on cognition. We are uncertain about effects on social behaviour and about long-term effects. Future studies should examine the duration of effects in relation to the overall duration of treatment and the number of sessions.

We found 22 trials to include in the review and we were able to combine results for at least some outcomes from 890 people. All of the people in the trials stayed in nursing homes or hospitals. Some trials compared music-based treatments with usual care, and some compared them with other activities, such as cooking or painting. The quality of the trials and how well they were reported varied, and this affected our confidence in the results. First, we looked at outcomes immediately after a course of therapy ended. From our results, we could be moderately confident that music-based treatments improve symptoms of depression and overall behavioural problems, but not specifically agitated or aggressive behaviour. They may also improve anxiety and emotional well-being including quality of life, although we were less confident about these results. They may have little or no effect on cognition. We had very little confidence in our results on social interaction. Some studies also looked to see whether there were any lasting effects four weeks or more after treatment ended. However, there were few data and we were uncertain or very uncertain about the results. Further trials are likely to have a significant impact on what we know about the effects of music-based treatments for people with dementia, so continuing research is important.

10.1002/14651858.CD003477.pub4

cochrane-simplification-train-2216

cochrane-simplification-train-2216

We identified one randomized controlled trial (CCLG-ENSG-5) that included 262 patients with high-risk neuroblastoma who were randomized to receive either rapid COJEC (N = 130) or standard OPEC/COJEC (N = 132) induction chemotherapy. We graded the evidence as low quality; we downgraded for risk of bias and imprecision. There was no clear evidence of a difference between the treatment groups in complete response (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.71 to 1.38), treatment-related mortality (RR 1.21, 95% CI 0.33 to 4.39), overall survival (hazard ratio (HR) 0.83, 95% CI 0.63 to 1.10), and event-free survival (HR 0.86, 95% CI 0.65 to 1.13). We calculated the HRs using the complete follow-up period of the trial. Febrile neutropenia (two or more episodes), proven fungal infections, septicemia (one or more episodes), gastrointestinal toxicity (grade 3 or 4), renal toxicity (glomerular filtration rate < 80 ml/min per body surface area of 1.73 m2), neurological toxicity (grade 3 or 4), and ototoxicity (Brock grade 2 to 4) were addressed as early toxicities (during pre-operative chemotherapy). For febrile neutropenia, septicemia, and renal toxicity, a statistically significant difference in favor of the standard treatment arm was identified; for all other early toxicities no clear evidence of a difference between treatment groups was identified. With regard to late non-hematological toxicities (median follow-up 12.7 years; range 6.9 to 16.5 years), the study provided data on any complication, renal toxicity (glomerular filtration rate < 80 ml/min per body surface area of 1.73m2), ototoxicity (Brock grade 1 to 4), endocrine complications, neurocognitive complications (i.e. behavioral, speech, or learning difficulties), and second malignancies. For endocrine complications and neurocognitive complications, a statistically significant difference in favor of the rapid COJEC arm was found; for all other late non-hematological toxicities no clear evidence of a difference between treatment groups was identified. Data on progression-free survival and health-related quality of life were not reported. We identified one randomized controlled trial that evaluated rapid COJEC versus standard induction therapy in patients with high-risk neuroblastoma. No clear evidence of a difference in complete response, treatment-related mortality, overall survival, and event-free survival between the treatment alternatives was found. This could be the result of low power or too short a follow-up period. Results of both early and late toxicities were ambiguous. Information on progression-free survival and health-related quality of life were not available. This trial was performed in the 1990s. Since then, many changes in, for example, treatment and risk classification have occurred. Therefore, based on the currently available evidence, we are uncertain about the effects of rapid COJEC and standard induction therapy in patients with high-risk neuroblastoma. More research is needed for a definitive conclusion.

We identified one randomized controlled trial with 262 patients. We excluded other study designs as they give less reliable results. However, randomized studies are difficult to perform in children with neuroblastoma and other evidence might be available. In the identified randomized study, patients with high-risk neuroblastoma were randomized to receive either rapid COJEC or standard OPEC/OJEC induction chemotherapy. Complete response, treatment-related mortality, overall survival, and event-free survival were not different between the two treatment alternatives. Results of both early and late toxicities were not clear cut, for example, some early toxicities were in favor of the standard arm and some late non-hematological toxicities were in favor of the rapid COJEC arm. For other toxicities there was no evidence of a difference between the treatment arms. Data on progression-free survival and health-related quality of life were not reported. Not all biases could be ruled out in this study. Before definitive conclusions can be made more research is needed.

10.1002/14651858.CD010774.pub2

cochrane-simplification-train-2217

cochrane-simplification-train-2217

A total of 16 randomised controlled trials (n=2277) were included in the meta-analysis.Despite the size of this sample, the pooled 95% confidence intervals were rather wide and there were no statistically significant differences in efficacy, acceptability and tolerability when comparing milnacipran with other antidepressive agents. However, compared with TCAs, patients taking milnacipran were associated with fewer dropouts due to adverse events (OR 0.55; 95%CI 0.35 to 0.85). There was also some weak evidence to suggest that patients taking milnacipran experienced fewer adverse events of sleepiness/ drowsiness, dry mouth or constipation compared with TCAs. Currently, there is inadequate evidence to conclude whether milnacipran is superior, inferior or the same as other antidepressive agents in terms of efficacy, acceptability and tolerability in the acute phase treatment of major depression. However, there is some evidence in favour of milnacipran over TCAs in terms of dropouts due to adverse events (acceptability) and the rates of experiencing adverse events (tolerability). Information about other clinically meaningful outcomes such as cost-effectiveness and social functioning, including the ability to return to work, is lacking. Further study is needed to answer whether milnacipran would be the better choice of antidepressant for acute major depression.

Major depression, also known as major depressive disorder or unipolar depression, is a common mental disorder characterised by a combination of symptoms that interfere with a person's ability to work, sleep, study, eat, and enjoy pleasurable activities. An episode of major depression may occur only once in a person's lifetime, but more often, it recurs throughout a person's life. Antidepressant drugs are frequently used as first-line treatment for major depression in primary and secondary care settings. Milnacipran, a dual serotonin-norepinephrine reuptake inhibitor, is one of the antidepressant drugs that clinicians use for routine depression care in some countries. This systematic review investigated the efficacy, acceptability and tolerability of milnacipran compared to that of other antidepressive agents in the acute phase treatment of major depression. A total of 16 randomised controlled trials (2277 participants) were included in this review. When we brought together the results of approximately 2000 patients, we were unable to say whether milnacipran is better, worse or the same when compared to other antidepressive agents used in practice in terms of efficacy, acceptability and tolerability. However, there is some evidence that fewer people taking milnacipran stop taking the drug ('drop out') due to side effects and fewer people taking milnacipran experience side effects such as sleepiness, dry mouth or constipation than do people who take tricyclic antidepressants.

10.1002/14651858.CD006529.pub2

cochrane-simplification-train-2218

cochrane-simplification-train-2218

Two randomized controlled trials (331 participants) met the inclusion criteria. They were conducted in the 1970s and 1980s with follow-up reports available after 18 months, three years, and five years; one trial also reported 10 years follow up. Completeness of follow up varied at the different time points, with less than 80% of participants available for analysis at several time points. There was no statistically significant difference for any of the outcome measures: kyphosis angle, neurological deficit (none went on to develop this), bony fusion, absence of spinal tuberculosis, death from any cause, activity level regained, change of allocated treatment, or bone loss. Neither trial reported on pain. Of the 130 participants allocated to chemotherapy only, 12 had a neurological deficit and five needed a decompression operation. One trial suggested that an initial kyphosis angle greater than 30° is likely to deteriorate, especially in children. The two included trials had too few participants to be able to say whether routine surgery might help. Although current medication and operative techniques are now far more advanced, these results indicate that routine surgery cannot be recommended unless within the context of a large, well-conducted randomized controlled trial. Clinicians may judge that surgery may be clinically indicated in some groups of patients. Future studies need to address these topics as well as the patient's view of their disease and treatment.

This review of trials found there were insufficient numbers of participants in the two trials located (331 participants) to be able to say if routine surgery early on was of overall benefit. Further trials are needed and such trials should assess the pain that people suffer and their views of the disease and treatment.

10.1002/14651858.CD004532.pub2

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cochrane-simplification-train-2219

Twenty-four studies were identified that involved acupuncture for endometriosis; however only one trial, enrolling 67 participants, met all the inclusion criteria. The single included trial defined pain scores and cure rates according to the Guideline for Clinical Research on New Chinese Medicine. Dysmenorrhoea scores were lower in the acupuncture group (mean difference -4.81 points, 95% confidence interval -6.25 to -3.37, P < 0.00001) using the 15-point Guideline for Clinical Research on New Chinese Medicine for Treatment of Pelvic Endometriosis scale. The total effective rate ('cured', 'significantly effective' or 'effective') for auricular acupuncture and Chinese herbal medicine was 91.9% and 60%, respectively (risk ratio 3.04, 95% confidence interval 1.65 to 5.62, P = 0.0004). The improvement rate did not differ significantly between auricular acupuncture and Chinese herbal medicine for cases of mild to moderate dysmenorrhoea, whereas auricular acupuncture did significantly reduce pain in cases of severe dysmenorrhoea. Data were not available for secondary outcomes measures. The evidence to support the effectiveness of acupuncture for pain in endometriosis is limited, based on the results of only a single study that was included in this review. This review highlights the necessity for developing future studies that are well-designed, double-blinded, randomised controlled trials that assess various types of acupuncture in comparison to conventional therapies.

This review examined the effectiveness of acupuncture for reducing pain in endometriosis; however only one study met our inclusion criteria. The data from the included study, involving 67 women, indicated that ear acupuncture is more effective compared to Chinese herbal medicine for reducing menstrual pain. The study did not report whether participants suffered any side effects from their treatments. Larger, well-designed studies comparing acupuncture with conventional therapies are necessary to confirm these results.

10.1002/14651858.CD007864.pub2

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cochrane-simplification-train-2220

The review contains four studies with a total of 149 participants. Two studies compared NPWT with dressings; one study compared NPWT with a series of gel treatments and one study compared NPWT with 'moist wound healing'. One study had a 24-week follow-up period, and two had a six-week follow-up period, the follow-up time was unclear for one study. Three of the four included studies were deemed to be at a high risk of bias from one or more 'Risk of bias' domains and all evidence was deemed to be of very low quality. Only one study reported usable primary outcome data (complete wound healing), but this had only 12 participants and there were very few events (only one participant healed in the study). There was little other useful data available from the included studies on positive outcomes such as wound healing or negative outcomes such as adverse events. There is currently no rigorous RCT evidence available regarding the effects of NPWT compared with alternatives for the treatment of pressure ulcers. High uncertainty remains about the potential benefits or harms, or both, of using this treatment for pressure ulcer management.

We searched the medical literature up to May 2015 for robust medical studies (randomised controlled studies) that compared NPWT with other treatments for pressure ulcers. We identified four studies involving a total of 149 participants. Two studies compared NPWT with dressings, one compared NPWT with a series of topical treatments and one study compared it with what was described only as 'moist wound healing'. The trials were small, and poorly described, of fairly short or unclear duration, and contained little in the way of useful data. As a result of the limited amount of research evidence available, we were not able to draw any conclusions regarding the potential value (or harm) of NPWT as a treatment for pressure ulcers. More, better quality research is needed if this is an important and relevant question for decision makers. This plain language summary is up-to-date as of May 2015.

10.1002/14651858.CD011334.pub2

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cochrane-simplification-train-2221

This review included 19 trials involving 2137 participants. Only five trials fulfilled the criteria of good methodological quality. One trial compared laser trabeculoplasty with topical beta-blocker to no intervention in early glaucoma. The risk of glaucoma progression was higher in the control group at six years of follow up (risk ratio (RR) 0.71 95% confidence interval (CI) 0.53 to 0.95). No difference in health-related quality of life was observed between the two groups. Three trials compared laser trabeculoplasty to medication (regimens used before the 1990s) in people with newly diagnosed OAG. The risk of uncontrolled intraocular pressure (IOP) was higher in the medication group compared to the trabeculoplasty group at six months and two years of follow up. Three trials compared laser trabeculoplasty with trabeculectomy. The risk of uncontrolled IOP was significantly higher in the trabeculoplasty group at six months but significant heterogeneity was observed at two years. Diode and selective laser are compared to argon laser trabeculoplasty in three trials and there is some evidence showing a comparable effect in controlling IOP at six months and one year of follow up. Evidence suggests that, in people with newly diagnosed OAG, the risk of uncontrolled IOP is higher in people treated with medication used before the 1990s when compared to laser trabeculoplasty at two years follow up. Trabeculoplasty is less effective than trabeculectomy in controlling IOP at six months and two years follow up. Different laser technology and protocol modalities were compared to the traditional laser trabeculoplasty and more evidence is necessary to determine if they are equivalent or not. There is no evidence to determine the effectiveness of laser trabeculoplasty compared to contemporary medication (prostaglandin analogues, topical anhydrase inhibitors and alpha2-agonists) and also with contemporary surgical techniques. Also there should be further investigation in to the effectiveness of laser trabeculoplasty in specific racial groups, specific diagnostic groups, such as pseudoexfoliation and pigmentary glaucoma and different stages of OAG. More research is also required determining cost-effectiveness of laser trabeculoplasty in the management of glaucoma.

This review included 19 trials (2137 participants). One trial compared laser trabeculoplasty associated with a hypotensive eyedrop with no intervention, and at six years of follow up the risk of visual field decay was greater in non treated participants. Three trials compared hypotensive eyedrops with trabeculoplasty, and the risk of uncontrolled IOP was greater at two years in the laser group. It is necessary to mention that the eyedrops used in these trials differ significantly from the ones used currently, since these trials were developed a decade ago. Three other trials compared trabeculoplasty with trabeculectomy and the risk of uncontrolled IOP was higher in the laser group at six months of follow up. There is some evidence showing that diode laser and selective trabeculoplasty have similar effect in controlling IOP when compared to argon laser trabeculoplasty. Comparisons of different lasers and different techniques of application were done in the remaining trials, but there is still not enough evidence to determine which is the best treatment protocol. Further research is necessary to compare trabeculoplasty with new hypotensive eyedrops and also the results of laser therapy in people of different ethnicities, since some studies suggest that they have a different response to this kind of laser therapy. More research is required to analyse cost-effectiveness of these interventions.

10.1002/14651858.CD003919.pub2

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cochrane-simplification-train-2222

A total of three studies involving 466 participants were included. There was no statistically significant difference between the asthma clinic group and the control group for most outcomes (primary outcomes: asthma exacerbations leading to hospitalisation or accident and emergency (A&E) visit, use of reliever and preventer medication, quality of life; secondary outcomes: symptoms, time lost from work and withdrawals from the intervention or usual care). However, the confidence intervals were wide for all outcomes and there was substantial heterogeneity between the studies for both A&E visits and time lost from work. One study (101 patients) looked at nocturnal awakenings due to asthma and found a statistically significant reduction in the number of patients reporting this symptom in the asthma clinic group compared to the usual care group (OR 0.31; 95% CI 0.12 to 0.77). There were no studies looking at the secondary outcome of exacerbations requiring oral steroids. There is limited evidence of efficacy for primary care based asthma clinics, and firm conclusions cannot be formed until more good quality trials have been carried out.

This review aimed to explore this question and included three studies with a total of 466 participants. These studies did not find any overall difference between asthma clinic and usual clinical practice care by a general practitioner for the following outcomes: A&E department visits for asthma, use of reliever or preventer medication for asthma and quality of life measures, but there was considerable uncertainty about these results. One study found that there was a reduction in nocturnal awakening due to asthma in the asthma clinic group compared to control but no difference in other symptom outcomes reported. Given the limited evidence found in this review, we believe that there is a need for further evidence in order to assess the effectiveness of asthma clinics.

10.1002/14651858.CD003533.pub2

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cochrane-simplification-train-2223

The review included seven studies, involving 380 adults. Of the 380 randomised participants, 348 completed the studies. Due to differences in outcomes reported among the seven studies, we could only perform limited meta-analysis for both the short-term ICS use (6 months or less) and the longer-term ICS use (> 6 months). During stable state in the short-term group (ICS for 6 months or less), based on the two studies from which data could be included, there were no significant differences from baseline values in the forced expiratory volume in the first second (FEV1) at the end of the study (mean difference (MD) -0.09, 95% confidence interval (CI) -0.26 to 0.09) and forced vital capacity (FVC) (MD 0.01 L, 95% CI -0.16 to 0.17) in adults on ICS (compared to no ICS). Similarly, we did not find any significant difference in the average exacerbation frequency (MD 0.09, 95% CI -0.61 to 0.79) or health-related quality of life (HRQoL) total scores in adults on ICS when compared with no ICS, though data available were limited. Based on a single non-placebo controlled study from which we could not extract clinical data, there was marginal, though statistically significant improvement in sputum volume and dyspnoea scores on ICS. The single study on long-term outcomes (over 6 months) that examined lung function and other clinical outcomes, showed no significant effect of ICS on any of the outcomes. We could not draw any conclusion on adverse effects due to limited available data. Despite the authors of all seven studies stating they were double-blind, we judged one study (in the short duration ICS) as having a high risk of bias based on blinding, attrition and reporting of outcomes. The GRADE quality of evidence was low for all outcomes (due to non-placebo controlled trial, indirectness and imprecision with small numbers of participants and studies). This updated review indicates that there is insufficient evidence to support the routine use of ICS in adults with stable state bronchiectasis. Further, we cannot draw any conclusion for the use of ICS in adults during an acute exacerbation or in children (for any state), as there were no studies.

We included studies that compared ICS with no ICS, or with a placebo (i.e. a medication made to look the same as ICS but with no active ingredients). We only included studies where it was decided at random who would receive ICS and who would not. The participants included in the seven studies were 380 adults who had bronchiectasis diagnosed by symptoms or from a detailed lung scan (computed tomography (CT)). We did not include studies that involved participants with cystic fibrosis, which can also cause bronchiectasis. Although we planned to include studies involving children with bronchiectasis, we did not find such studies. From available evidence up to June 2017, we found seven eligible studies involving adult participants that examined the role of ICS in bronchiectasis. The adults had stable bronchiectasis - they were not having a flare-up at the start of the study. We were able to include results from two studies that gave ICS for less than six months to adults with stable bronchiectasis. ICS did not make a difference to lung function, number of exacerbations during the study or quality of life. In a different study, which also gave ICS for less than six months, we found a small reduction in sputum (phlegm) and improvement in breathlessness. However, as these results were from a study which did not use a placebo we cannot be certain about them. The single study on long-term use of ICS (i.e. for over 6 months) showed no meaningful benefit of ICS for any of the outcomes. There were no studies conducted when the participants were having a flare-up of their bronchiectasis. There were also no studies that involved children with bronchiectasis. Importantly, we do not know if ICS are linked to more unwanted side effects, because the studies did not provide much information about this. The review found that there is not enough evidence for the routine use of ICS in adults with stable bronchiectasis. We can make no conclusions about the use of ICS for flare-ups of bronchiectasis, or about their use in children, because we did not find any studies. Overall, we judged the quality of evidence to be low. We were concerned because the largest study, which showed some benefits, did not use a placebo. This means that participants and staff in the study would have known who was getting ICS and who was not, which could affect the results. Also, our confidence was reduced because we only found a small number of studies to include in our review and some of the studies may have included people with other types of lung disease, in addition to bronchiectasis.

10.1002/14651858.CD000996.pub3

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cochrane-simplification-train-2224

We included 28 small, low quality studies (29 reports) involving 2564 participants. Of 20 studies (21 reports) comparing morphine with placebo, nine studies with adequate data were included in the meta-analysis. Overall, the risk of bias was unclear. Overall, the quality of the evidence assessed using GRADE was low to very low, downgraded primarily due to risk of bias, small study size, and imprecision. No statistical difference was found between 1 mg IA morphine and placebo in pain intensity (visual analogue scale (VAS)) at early phase (zero to two hours) (mean difference (MD) -0.50, 95% CI -1.15 to 0.14; participants = 297; studies = 7; low quality evidence), medium phase (two to six hours) (MD -0.47, 95% CI -1.09 to 0.14; participants = 297; studies = 7; low quality evidence) and late phase (six to 30 hours) (MD -0.88, 95% CI -1.81 to 0.04; participants = 297; studies = 7; low quality evidence). No significant difference was found between 1 mg and 2 mg morphine for pain intensity at early phase (MD -0.56, 95% CI -1.93 to 0.81; participants = 105; studies = 2; low quality evidence), while 4 mg/5 mg morphine provided better analgesia than 1 mg morphine at late phase (MD 0.67, 95% CI 0.08 to 1.25; participants = 97; studies = 3; low quality evidence). IA morphine was not better than local anaesthetic agents at early phase (MD 1.43, 95% CI 0.49 to 2.37; participants = 248; studies = 5; low quality evidence), NSAIDs at early phase (MD 0.95, 95% CI -0.95 to 2.85; participants = 80; studies = 2; very low quality evidence), sufentanil, fentanyl or pethidine for pain intensity. IA morphine was similar to intramuscular (IM) morphine for pain intensity at early phase (MD 0.21, 95% CI -0.48 to 0.90; participants = 72; studies = 2; very low quality evidence). Meta-analysis indicated that there was no difference between IA morphine and placebo or bupivacaine in time to first analgesic request. Eleven out of 20 studies comparing morphine with placebo reported adverse events and no statistical difference was obtained regarding the incidence of adverse events (risk ratio (RR) 1.09, 95% CI 0.51 to 2.36; participants = 314; studies = 8; low quality evidence). Seven of 28 studies reported participants' withdrawal. There were not enough data for withdrawals to be able to perform meta-analysis. We have not found high quality evidence that 1 mg IA morphine is better than placebo at reducing pain intensity at early, medium or late phases. No statistical difference was reported between IA morphine and placebo regarding the incidence of adverse events. The relative effects of 1 mg morphine when compared with IA bupivacaine, NSAIDs, sufentanil, fentanyl and pethidine are uncertain. The quality of the evidence is limited by high risk of bias and small size of the included studies, which might bias the results. More high quality studies are needed to get more conclusive results.

In May 2015, this review identified 28 small, low quality studies involving 2564 participants looking at intra-articular morphine for pain relief after knee arthroscopy. From 9/20 studies we did not find evidence that intra-articular morphine given at a dose of 1 mg was better than placebo for pain relief. From the limited evidence available we were unable to determine how intra-articular morphine compared with morphine injected into the muscle (intra-muscular morphine). There was also low quality evidence for the effects of 1 mg intra-articular morphine compared with intra-articular bupivacaine, non-steroidal anti-inflammatory drugs (NSAIDs), sufentanil, fentanyl and pethidine, so we were unsure which worked best. We were unable to determine how similar the rates of side effects such as nausea and vomiting were between intra-articular morphine and placebo. Overall, the quality of the evidence was low. Future research should focus on finding effective analgesics for knee arthroscopy.

10.1002/14651858.CD008918.pub2

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cochrane-simplification-train-2225

One randomised controlled trial has compared pramipexole with bromocriptine using a double-blind, parallel group, multicentre design. It was not powered to examine differences between active treatment arms. There was a larger reduction in off time with pramipexole therapy compared with bromocriptine (weighted mean difference 1.4 hours; 0, 2.8, 95% CI). No differences occurred in dyskinesia rating scale, dyskinesia as an adverse event or UPDRS complication score. The UPDRS ADL and motor scores showed similar improvements compared to placebo with both agonists. Levodopa dose reduction was similar with both agonists. Subscales of the Functional Status Questionnaire showed significant improvements compared to placebo with both agonists. The finding that the EuroQol improved significantly compared with placebo with pramipexole but not bromocriptine should be treated with caution. Dopaminergic adverse events were similar with each agonist, as was the all cause withdrawal rate. Although pramipexole and bromocriptine improved off time and reduced parkinsonian motor impairments and disability compared with placebo, no conclusions regarding their comparative effectiveness and safety can be drawn as this single trial did not have adequate power to assess such differences. Further larger trials are required to examine this issue in the future.

One trial compared pramipexole with bromocriptine but this was not designed to examine differences between the two treatments as there were too few patients included. However, there was a larger reduction in the time patients spent in the immobile off state with pramipexole therapy compared with bromocriptine by an average of 1.4 hours. No differences occurred in dyskinesia rating scale, dyskinesia as a side effect or Unified Parkinson's Disease Rating Scale (UPDRS) complication score. The UPDRS activities of daily living and motor scores showed similar improvements compared to placebo with both agonists. Levodopa dose reduction was similar with both agonists. Subscales of a quality of life measure, the Functional Status Questionnaire, showed significant improvements compared to placebo with both agonists. The finding that another quality of life scale, the EuroQol, improved significantly compared with placebo with pramipexole but not bromocriptine should be treated with caution. Side effects such as nausea, vomiting, and faintness were similar with each agonist, as was the withdrawal from treatment rate. No conclusions regarding the comparative effectiveness and safety of pramipexole versus bromocriptine can be drawn as this single trial did not have adequate numbers of patients to assess such differences. Further larger trials are required to examine this issue in the future.

10.1002/14651858.CD002259

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cochrane-simplification-train-2226

Seventeen studies (831 participants) met the inclusion criteria. All the studies had some shortcomings, such as small sample size, under-reporting of methods and data, and lack of blinding. OA versus control appliances (six studies): OA reduced daytime sleepiness in two crossover trials (ESS score -1.81; 95%CI -2.72 to -0.90), and improved apnoea-hypopnoea index (AHI) (-10.78 events/hr; 95% CI-15.53 to -6.03 parallel group data - five studies). OA versus CPAP (ten studies): There was no statistically significant difference in symptoms for either parallel or crossover studies, although OAs were less effective than CPAP in reducing apnoea-hypopnoea index in parallel and crossover studies. CPAP was more effective at improving minimum arterial oxygen saturation during sleep compared with OA. In two small crossover studies, participants preferred OA therapy to CPAP. OA versus corrective upper airway surgery (one study): Symptoms of daytime sleepiness were initially lower with surgery, but this difference disappeared at 12 months. AHI did not differ significantly initially, but did so after 12 months in favour of OA. There is increasing evidence suggesting that OA improves subjective sleepiness and sleep disordered breathing compared with a control. CPAP appears to be more effective in improving sleep disordered breathing than OA. The difference in symptomatic response between these two treatments is not significant, although it is not possible to exclude an effect in favour of either therapy. Until there is more definitive evidence on the effectiveness of OA in relation to CPAP, with regard to symptoms and long-term complications, it would appear to be appropriate to recommend OA therapy to patients with mild symptomatic OSAH, and those patients who are unwilling or unable to tolerate CPAP therapy. Future research should recruit patients with more severe symptoms of sleepiness, to establish whether the response to therapy differs between subgroups in terms of quality of life, symptoms and persistence with usage. Long-term data on cardiovascular health are required.

This review found that OA should not be considered as first choice therapy for OSAH, where symptoms and sleep disruption are severe. There has not been a sufficient amount of research that examines the effects of OA compared with CPAP in terms of symptoms and quality of life. Although CPAP was clearly more effective at reducing the disruption to sleep, some people with OSAH may prefer using them if they are found to be tolerable and more convenient than CPAP. When an active OA was compared with an inactive OA , there were improvements in daytime sleepiness and apnoea/hypopnoea severity. OA may be more effective than corrective upper airway surgery. Further research should consider whether people with more distinctly severe symptoms respond in a similar way to those patients represented in the studies we have included in the review.

10.1002/14651858.CD004435.pub3

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cochrane-simplification-train-2227

We included 39 parallel randomised controlled trials (RCTs) involving adults and children with asthma, 28 of which (n = 16,303) contributed data to at least one meta-analysis. Follow-up ranged from two months to two years (median six months), and trials were conducted mainly in high-income countries. Most studies reported some measure of adherence to ICS and a variety of other outcomes such as quality of life and asthma control. Studies generally were at low or unclear risk of selection bias and at high risk of biases associated with blinding. We considered around half the studies to be at high risk for attrition bias and selective outcome reporting. We classified studies into four comparisons: adherence education versus control (20 studies); electronic trackers or reminders versus control (11 studies); simplified drug regimens versus usual drug regimens (four studies); and school-based directly observed therapy (three studies). Two studies are described separately. All pooled results for adherence education, electronic trackers or reminders and simplified regimens showed better adherence than controls. Analyses limited to studies using objective measures revealed that adherence education showed a benefit of 20 percentage points over control (95% confidence interval (CI) 7.52 to 32.74; five studies; low-quality evidence); electronic trackers or reminders led to better adherence of 19 percentage points (95% CI 14.47 to 25.26; six studies; moderate-quality evidence); and simplified regimens led to better adherence of 4 percentage points (95% CI 1.88 to 6.16; three studies; moderate-quality evidence). Our confidence in the evidence was reduced by risk of bias and inconsistency. Improvements in adherence were not consistently translated into observable benefit for clinical outcomes in our pooled analyses. None of the intervention types showed clear benefit for our primary clinical outcomes - exacerbations requiring an oral corticosteroid (OCS) (evidence of very low to low quality) and asthma control (evidence of low to moderate quality); nor for our secondary outcomes - unscheduled visits (evidence of very low to moderate quality) and quality of life (evidence of low to moderate quality). However, some individual studies reported observed benefits for OCS and use of healthcare services. Most school or work absence data were skewed and were difficult to interpret (evidence of low quality, when graded), and most studies did not specifically measure or report adverse events. Studies investigating the possible benefit of administering ICS at school did not measure adherence, exacerbations requiring OCS, asthma control or adverse events. One study showed fewer unscheduled visits, and another found no differences; data could not be combined. Pooled results suggest that a variety of interventions can improve adherence. The clinical relevance of this improvement, highlighted by uncertain and inconsistent impact on clinical outcomes such as quality of life and asthma control, is less clear. We have low to moderate confidence in these findings owing to concerns about risk of bias and inconsistency. Future studies would benefit from predefining an evidence-based 'cut-off' for acceptable adherence and using objective adherence measures and validated tools and questionnaires. When possible, covert monitoring and some form of blinding or active control may help disentangle effects of the intervention from effects of inclusion in an adherence trial.

We found 39 studies including more than 16,000 adults and children with asthma who were taking a steroid inhaler. Most studies collected data at six months, so we can really apply the messages in this review only over six months - we cannot say whether these methods are effective in a few years time, for example. We searched multiple sources for relevant studies. This review is current as of November 2016. Different studies tried different ways to help people take their inhaler more regularly. We grouped studies according to four ways of helping people take their inhaler: providing education about adherence (20 studies); using electronic monitoring or reminders to take the inhaler (11 studies); making the drug easier to take (e.g. once instead of twice a day, one inhaler instead of two) (four studies); and giving the inhaler during school hours (three studies). We mainly looked for whether strategies helped people to take their inhaler as prescribed, and whether people had fewer asthma attacks and better asthma control. People who were given education were better at taking their inhaler than controls; 20% more people took their treatment (likely to be somewhere between 8% and 33% more). Those given trackers or electronic reminders were 19% better at using their inhaler than controls (14% and 25%). People who were given an easier way of taking their inhaler (e.g. fewer times a day) were only 4% better than those who carried on as usual (2% and 6%). Unfortunately, these efforts to help people take their inhaler as prescribed generally did not lead to obvious benefit for things like asthma control and number of attacks, but in most cases, we could not tell either way. We also did not see a difference for quality of life or time people needed off school or work, but the evidence was often uncertain. Studies investigating the possible benefit of giving children their inhaler during school hours did not actually measure how often they missed doses. It's difficult to tell whether these different strategies are worth using because studies were quite different from one other. This variation means that we cannot be sure what the real benefit is, beyond improving adherence. Sometimes we did not find enough studies to detect a difference between groups. The fact that most people knew which group they were in also reduced our confidence in the findings because this can affect things like how positively people respond to questionnaires. We had concerns about how many people dropped out of about half the studies, and we are uncertain whether studies reported everything they measured. The studies we found suggest that various strategies can help people with asthma take their inhaler better, compared with "control" (e.g. usual asthma care). However, many of these studies were quite different from one another, and we are not certain about whether people will find that their asthma is improved as a result of this approach.

10.1002/14651858.CD012226.pub2

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cochrane-simplification-train-2228

We included two studies, both from the United States. People offered health insurance information and application support by community-based case managers were probably more likely to enrol their children into health insurance programmes (risk ratio (RR) 1.68, 95% confidence interval (CI) 1.44 to 1.96, moderate quality evidence) and were probably more likely to continue insuring their children (RR 2.59, 95% CI 1.95 to 3.44, moderate quality evidence). Of all the children that were insured, those in the intervention group may have been insured quicker (47.3 fewer days, 95% CI 20.6 to 74.0 fewer days, low quality evidence) and parents may have been more satisfied on average (satisfaction score average difference 1.07, 95% CI 0.72 to 1.42, low quality evidence). In the second study applications were handed out in emergency departments at hospitals, compared to not handing out applications, and may have had an effect on enrolment (RR 1.5, 95% CI 1.03 to 2.18, low quality evidence). Community-based case managers who provide health insurance information, application support, and negotiate with the insurer probably increase enrolment of children in health insurance schemes. However, the transferability of this intervention to other populations or other settings is uncertain. Handing out insurance application materials in hospital emergency departments may help increase the enrolment of children in health insurance schemes. Further studies evaluating the effectiveness of different strategies for expanding health insurance coverage in vulnerable population are needed in different settings, with careful attention given to study design.

Both studies in this review took place in the USA and were aimed at uninsured children. In the first study, case managers contacted the families of uninsured Latin American children, gave them information about health insurance, helped them apply, and helped them appeal when a wrong decision was made. In the second study, insurance application forms were handed out to the families of children visiting hospital emergency departments. In both studies, these families were compared to families who were not given additional information or support. The studies showed the following: People who are offered health insurance information and application support: - are probably more likely to enrol their children into health insurance programmes (moderate quality evidence); - are probably more likely to continue insuring their children (moderate quality evidence); - may be quicker at getting insurance (low quality evidence); - may be more satisfied with the process of enrolment (low quality evidence). People who are given insurance application forms in the emergency departments of hospitals: - may be more likely to enrol their children into health insurance programmes (low quality evidence). No unwanted effects were reported in the studies. A possible unwanted effect might be that people could experience the information and support as annoying or unhelpful. However, in the one study that measured the parents’ satisfaction, people were more satisfied when given information and support. A summary of this review for policy-makers is availablehere

10.1002/14651858.CD008194.pub3

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cochrane-simplification-train-2229

Six trials (1422 participants) were included in the review. There was a high rate of failure to complete treatment on all treatments which may have biased the estimates of relative efficacy. Olanzapine was superior to placebo at reducing manic symptoms as monotherapy (Young Mania Rating Scale (YMRS) - weighted mean difference (WMD): -5.94, 95% CI -9.09 to -2.80) and in combination with lithium/valproate (YMRS) (WMD -4.01, 95% confidence interval -6.06 to -1.96). Olanzapine monotherapy was superior at reducing psychotic symptoms (PANSS positive symptoms subscale WMD: -3.54, 95% CI -5.28 to -1.80). Olanzapine was superior to divalproex at reducing manic symptoms (standardised mean difference (SMD): -0.29, 95% CI -0.50 to -0.08). Olanzapine did not lead to a statistically higher rate of clinical response than haloperidol (RR: 1.03, 95% CI 0.77 to 1.38). Fewer patients discontinued treatment on olanzapine than placebo (RR: 0.62, 95% CI 0.48 to 0.80). Olanzapine caused greater weight gain than placebo (WMD 1.91Kg, 95% CI 1.29 to 2.53) and somnolence (RR: 2.13 95% CI 1.62 to 2.79) but not more depressive symptoms (RR: 0.95, 95% CI 0.65 to 1.40) or movement disorder (WMD: -0.33, 95% CI -0.74 to 0.09). Olanzapine caused more prolactin elevation than placebo (RR: 4.35 95%CI 1.77 to 10.70). Olanzapine caused greater weight gain (WMD: 1.54, 95% CI 1.02 to 2.05); somnolence (RR: 1.80 95% CI 1.32 to 2.46) and movement disorders (SAS - WMD: 0.72 95% CI 0.11 to 1.33) than divalproex but less nausea ( RR: 0.36 95% CI 0.20 to 0.65). Olanzapine caused more weight gain than haloperidol (RR: 3.59, 95% CI 1.49 to 8.64) but less movement disorder (EPS RR: 0.10, 95% CI 0.04 to 0.24). Olanzapine is an effective treatment for mania and may be more efficacious than divalproex, though leads to more weight gain. Clinicians should consider both the relative efficacy and the different incidence of specific adverse effects of available drugs.

High withdrawal rates from the trials limit the confidence that can be placed on the results. Olanzapine was superior to placebo in reduction of manic symptoms both as monotherapy and combined with mood stabilizers, though caused weight gain. Olanzapine was more efficacious than divalproex and caused less nausea but more weight gain, somnolence and movement disorders. Olanzapine was comparable to haloperidol in efficacy, caused less movement disorders but greater weight gain.

10.1002/14651858.CD004040

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cochrane-simplification-train-2230

We included ten papers reporting results from six intervention studies. Overall, design quality and analysis limited the risks of bias. Several CCT programmes provided strong evidence of a positive impact on the use of health services, nutritional status and health outcomes, respectively assessed by anthropometric measurements  and self-reported episodes of illness. It is hard to attribute these positive effects to the cash incentives specifically because other components may also contribute. Several studies provide evidence of positive impacts on the uptake of preventive services by children and pregnant women. We found no evidence about effects on health care expenditure. Conditional cash transfer programmes have been the subject of some well-designed evaluations, which strongly suggest that they could be an effective approach to improving access to preventive services. Their replicability under different conditions - particularly in more deprived settings - is still unclear because they depend on effective primary health care and mechanisms to disburse payments. Further rigorous evaluative research is needed, particularly where CCTs are being introduced in low income countries, for example in Sub-Saharan Africa or South Asia.

We found 29 papers on the impact of conditional cash transfers (CCT) on access to care and health outcomes. Of these, ten papers, reporting results from six studies, satisfied the inclusion criteria; four of these studies were randomised experiments. Despite a number of methodological weaknesses in some studies, overall the research evidence suggests that CCT schemes may result in a number of benefits to health for poor populations. Many conditional cash transfer programmes include a number of components, including incentivising attendance for health education, measurements of height and weight, immunisations and nutritional supplementation. Conditional cash transfer programmes appear to be an effective way to increase the uptake of preventive services and encourage some preventive behaviours. In some cases programmes have noted improvement of health outcomes, though it is unclear to which components this positive effect should be attributed.

10.1002/14651858.CD008137

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cochrane-simplification-train-2231

Five studies reported five comparisons of paraprofessionals versus professionals (n=106) and five comparisons of paraprofessionals versus control condition (n=220). No differences were found between paraprofessionals and professionals (SMD=0.09, 95% CI -0.23 to 0.40, p=0.58), and no significant heterogeneity. Studies comparing paraprofessionals versus control (mixed continuous and dichotomous data) showed a significant effect in favour of paraprofessionals (OR=0.34, 95% CI 0.13 to 0.88, p=0.03), but heterogeneity was indicated (I²=60.9%, Chi²= 10.24, df=4, p=0.04). After correction for heterogeneity and removing one study of low quality, the pooling of data from three studies (n=128; mixed gender; women) indicated no significant difference in effect between paraprofessionals and professionals (SMD=0.13, 95% CI -0.39 to 0.64; p=0.63) and a strongly significant pooled effect for three studies (n=188; women) favouring paraprofessionals over the control condition (OR=0.30, 95% CI 0.18 to 0.48, p<0.00001), and homogeneity indicated between studies (I²=0%, Chi²=0.47, df=2, p=0.79). The few studies included in the review did not allow conclusions about the effect of paraprofessionals compared to professionals, but three studies (women only) indicated a significant effect for paraprofessionals (all volunteers) compared to no treatment. The evidence to date may justify the development and evaluation of programs incorporating paraprofessionals in treatment programs for anxiety and depressive disorders.

This review investigated the effectiveness of any kind of psychological treatment conducted by paraprofessionals.The few studies found did not allow conclusions about the effect of paraprofessionals compared to professionals in the treatment of anxiety and depressive disorders. Pooling data from three studies, involving women only, indicated a significant effect for paraprofessionals compared to no treatment. The evidence so far may justify the development and evaluation of programs incorporating paraprofessionals in treatment programs for anxiety and depressive disorders.

10.1002/14651858.CD004688.pub2

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cochrane-simplification-train-2232

The only point-of-care biomarker of infection currently available to primary care identified in this review was C-reactive protein. We included six trials (3284 participants; 139 children) that evaluated a C-reactive protein point-of-care test. The available information was from trials with a low to moderate risk of bias that address the main objectives of this review. Overall a reduction in the use of antibiotic treatments was found in the C-reactive protein group (631/1685) versus standard of care (785/1599). However, the high level of heterogeneity and the statistically significant test for subgroup differences between the three RCTs and three cluster-RCTs suggest that the results of the meta-analysis on antibiotic use should be interpreted with caution and the pooled effect estimate (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.66 to 0.92; I2 statistic = 68%) may not be meaningful. The observed heterogeneity disappeared in our preplanned subgroup analysis based on study design: RR 0.90, 95% CI 0.80 to 1.02; I2 statistic = 5% for RCTs and RR 0.68, 95% CI 0.61 to 0.75; I2 statistic = 0% for cluster-RCTs, suggesting that this was the cause of the observed heterogeneity. There was no difference between using a C-reactive protein point-of-care test and standard care in clinical recovery (defined as at least substantial improvement at day 7 and 28 or need for re-consultations day 28). However, we noted an increase in hospitalisations in the C-reactive protein group in one study, but this was based on few events and may be a chance finding. No deaths were reported in any of the included studies. We classified the quality of the evidence as moderate according to GRADE due to imprecision of the main effect estimate. A point-of-care biomarker (e.g. C-reactive protein) to guide antibiotic treatment of ARIs in primary care can reduce antibiotic use, although the degree of reduction remains uncertain. Used as an adjunct to a doctor's clinical examination this reduction in antibiotic use did not affect patient-reported outcomes, including recovery from and duration of illness. However, a possible increase in hospitalisations is of concern. A more precise effect estimate is needed to assess the costs of the intervention and compare the use of a point-of-care biomarker to other antibiotic-saving strategies.

We included six studies with a total of 3284 participants with ARIs from primary care settings (point-of care test: C-reactive protein). Two of the included studies received direct financial support from manufacturers. The evidence is current to January 2014. The only point-of-care biomarker of infection currently available to primary care identified in the review was C-reactive protein. A reduction in antibiotic use is likely to be achieved by a C-reactive protein point-of-care test but due to differences in the designs of the included studies, it was not possible to obtain a precise effect estimate of the reduction. There were no deaths in the studies and we did not find evidence suggesting that time to recovery from ARIs and their duration were longer, nor that levels of patient satisfaction or number of re-consultations were affected in the C-reactive protein group. However, a possible increase in the risk of hospital admission cannot be ruled out. We ranked the evidence as of moderate quality according to the GRADE levels due to an imprecise effect estimation. Used as an adjunct to a doctor's clinical examination point-of-care tests (e.g. C-reactive protein) can reduce antibiotic use in ARIs in general practice. The possibility of an increased risk of hospital admission suggests that care must be taken in how these tests are used. A more precise effect estimate is needed to assess the costs of the intervention and compare the use of a point-of-care biomarker to other antibiotic-saving strategies.

10.1002/14651858.CD010130.pub2

cochrane-simplification-train-2233

cochrane-simplification-train-2233

We included 83 trials in this review. The majority of trials (67) were carried out in school settings with eight in colleges or universities, four in clinical settings, three in the community and four in mixed settings. Twenty-nine trials were carried out in unselected populations and 53 in targeted populations. For the primary outcome of depression diagnosis at medium-term follow-up (up to 12 months), there were 32 trials with 5965 participants and the risk of having a diagnosis of depression was reduced for participants receiving an intervention compared to those receiving no intervention (risk difference (RD) -0.03, 95% confidence interval (CI) -0.05 to -0.01; P value = 0.01). We rated this evidence as moderate quality according to the GRADE criteria. There were 70 trials (73 trial arms) with 13,829 participants that contributed to the analysis for the primary outcome of depression symptoms (self-rated) at the post-intervention time point, with results showing a small but statistically significant effect (standardised mean difference (SMD) -0.21, 95% CI -0.27 to -0.15; P value < 0.0001). This effect persisted to the short-term assessment point (up to three months) (SMD -0.31, 95% CI -0.45 to -0.17; P value < 0.0001; 16 studies; 1558 participants) and medium-term (4 to 12 months) assessment point (SMD -0.12, 95% CI -0.18 to -0.05; P value = 0.0002; 53 studies; 11,913 participants); however, the effect was no longer evident at the long-term follow-up. We rated this evidence as low to moderate quality according to the GRADE criteria. The evidence from this review is unclear with regard to whether the type of population modified the overall effects; there was statistically significant moderation of the overall effect for depression symptoms (P value = 0.0002), but not for depressive disorder (P value = 0.08). For trials implemented in universal populations there was no effect for depression diagnosis (RD -0.01, 95% CI -0.03 to 0.01) and a small effect for depression symptoms (SMD -0.11, 95% CI -0.17 to -0.05). For trials implemented in targeted populations there was a statistically significantly beneficial effect of intervention (depression diagnosis RD -0.04, 95% CI -0.07 to -0.01; depression symptoms SMD -0.32, 95% CI -0.42 to -0.23). Of note were the lack of attention placebo-controlled trials in targeted populations (none for depression diagnosis and four for depression symptoms). Among trials implemented in universal populations a number used an attention placebo comparison in which the intervention consistently showed no effect. Overall the results show small positive benefits of depression prevention, for both the primary outcomes of self-rated depressive symptoms post-intervention and depression diagnosis up to 12 months (but not beyond). Estimates of numbers needed to treat to benefit (NNTB = 11) compare well with other public health interventions. However, the evidence was of moderate to low quality using the GRADE framework and the results were heterogeneous. Prevention programmes delivered to universal populations showed a sobering lack of effect when compared with an attention placebo control. Interventions delivered to targeted populations, particularly those selected on the basis of depression symptoms, had larger effect sizes, but these seldom used an attention placebo comparison and there are practical difficulties inherent in the implementation of targeted programmes. We conclude that there is still not enough evidence to support the implementation of depression prevention programmes. Future research should focus on current gaps in our knowledge. Given the relative lack of evidence for universal interventions compared with attention placebo controls and the poor results from well-conducted effectiveness trials of universal interventions, in our opinion any future such trials should test a depression prevention programme in an indicated targeted population using a credible attention placebo comparison group. Depressive disorder as the primary outcome should be measured over the longer term, as well as clinician-rated depression. Such a trial should consider scalability as well as the potential for the intervention to do harm.

We included 83 studies (in particular randomised controlled trials) of evidence-based psychotherapy interventions (cognitive behavioural therapy (CBT) and third wave CBT, interpersonal therapy) that had the specific aim of preventing the onset of depressive disorder. For the primary outcome of depression diagnosis at medium-term follow-up (up to 12 months), there were 32 trials with 5965 participants and for the primary outcome of depression symptoms (self-rated) there were 73 trials with 13,829 participants. What does the evidence from the review tell us? We found that, compared with any comparison group, psychological depression prevention programmes have small positive benefits on depression prevention. There were some problems with the way the trials were done and in particular the results showed that compared to an attention placebo comparison group (a control intervention that controls for non-specific factors like involvement in a trial and attention from researchers), these programmes had no effect. There is still not enough evidence to support the implementation of depression prevention programmes. However, based on the effects seen for targeted depression prevention programmes (albeit with inadequate control groups), we recommend that further research be undertaken to test the effectiveness of depression prevention programmes in populations of young people who already have some symptoms of depression. Such trials should compare the intervention to an attention placebo comparison group and measure whether depressive diagnosis is prevented in the long term. They also need to consider whether the approach is something that can be implemented in the real world. In addition, they should consider and measure whether the intervention produces harmful outcomes.

10.1002/14651858.CD003380.pub4

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cochrane-simplification-train-2234

We included three studies (179 participants) comparing LESS-DN with laparoscopic donor nephrectomy. There were no significant differences between LESS-DN and laparoscopic donor nephrectomy for mean operative time (2 studies, 79 participants: MD 6.36 min, 95% CI -11.85 to 24.57), intra-operative blood loss (2 studies, 79 participants: MD -8.31 mL, 95% CI -23.70 to 7.09), or complication rates (3 studies, 179 participants: RD 0.05, 95% CI -0.04 to 0.14). Pain scores at discharge were significantly less in the LESS-DN group (2 studies, 79 participants: MD -1.19, 95% CI -2.17 to -0.21). For all other outcomes (length of hospital stay; length of time to return to normal activities; blood transfusions; conversion to another form of surgery; warm ischaemia time; total analgesic requirement; graft loss) there were no significant differences observed. Although risk of bias was assessed as low overall, one study was assessed at high risk of attrition bias. Given the small number and size of included studies it is uncertain whether LESS-DN is better than laparoscopic donor nephrectomy. Well designed and adequately powered RCTs are needed to better define the role of LESS-DN as a minimally invasive option for kidney donor surgery.

We searched to literature up to January 2016 and found three studies (reported in 5 publications that involved 179 participants) that compared these two types of kidney donor surgeries. LESS-DN was found to be as safe as standard keyhole surgical techniques; pain at discharge was significantly less with LESS-DN, however there were no other discernible benefits over the standard technique. Overall, we found there was a low risk of bias for all studies; however, funding sources were not reported in two or three studies, and there was high risk of attrition bias in one study. The small number of studies with few participants eligible for inclusion indicates a need for future research in this area.

10.1002/14651858.CD010850.pub2

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cochrane-simplification-train-2235

Thirteen trials were included. None measured an injury outcome. Two trials measured error, and the remaining trials used neuropsychological tests to assess cognitive performance. The trials assessing the impact on errors found that caffeine significantly reduced the number of errors compared to placebo. The pooled effect estimates on performance by cognitive domain suggest that, when compared to placebo, caffeine improved concept formation and reasoning (SMD -0.41; 95% CI -1.04 to 0.23), memory (SMD -1.08; 95% CI -2.07 to -0.09), orientation and attention (SMD -0.55; 95% CI -0.83 to -0.27) and perception (SMD -0.77; 95% CI -1.73 to 0.20); although there was no beneficial effect on verbal functioning and language skills (SMD 0.18; 95% CI -0.50 to 0.87). One trial comparing the effects of caffeine with a nap found that there were significantly less errors made in the caffeine group. Other trials comparing caffeine with other active interventions (for example nap, bright light, modafinil) found no significant differences. There is a high risk of bias for the adequacy of allocation concealment and presence of selective outcome reporting amongst the trials. Caffeine may be an effective intervention for improving performance in shift workers however, there are no trials from which we can assess its effect on injuries. The results largely originate from studies involving young participants under simulated conditions, and the extent to which the findings are generalisable to older workers and real world shift work is unclear. Based on the current evidence, there is no reason for healthy individuals who already use caffeine within recommended levels to improve their alertness to stop doing so. The assessment of the relative effects of caffeine to other potential countermeasures should be a focus of future research.

For this systematic review, the authors searched for randomised controlled trials which investigated the effects of caffeine on injury, error and cognitive performance in shift workers. They found 13 trials - none of the trials looked at the effect on injury, two trials measured error, while the remaining trials used neuropsychological tests to assess cognitive performance. The results of the trials suggest that compared to no intervention, caffeine can reduce the number of errors and improve cognitive performance in shift workers. No difference in effect was found by the trials comparing caffeine with other interventions (such as nap, bright light and modafinil). However, due to some methodological weaknesses of the trials, some caution is required when interpreting the results. The authors of the systematic review conclude that caffeine may be an effective intervention for improving performance in shift workers however, there are no trials from which they could assess its effect on injuries. Based on the current evidence, the review authors judge that there is no reason for healthy shift workers who already use caffeine within recommended levels to improve their alertness, to stop doing so. They go on to suggest that it would be useful for further trials to be undertaken to assess the effects of caffeine against other potential countermeasures.

10.1002/14651858.CD008508

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cochrane-simplification-train-2236

We identified 182 studies with a total of 16,855 included participants investigating outcomes of surgery for epilepsy. Nine studies were RCTs (including two that randomised participants to surgery or medical treatment (99 participants included in the two trials received medical treatment)). Risk of bias in these RCTs was unclear or high. Most of the remaining 173 non-randomised studies followed a retrospective design. We assessed study quality using the Effective Public Health Practice Project (EPHPP) tool and determined that most studies provided moderate or weak evidence. For 29 studies reporting multivariate analyses, we used the Quality in Prognostic Studies (QUIPS) tool and determined that very few studies were at low risk of bias across domains. In terms of freedom from seizures, two RCTs found surgery (n = 97) to be superior to medical treatment (n = 99); four found no statistically significant differences between anterior temporal lobectomy (ATL) with or without corpus callosotomy (n = 60), between subtemporal or transsylvian approach to selective amygdalohippocampectomy (SAH) (n = 47); between ATL, SAH and parahippocampectomy (n = 43) or between 2.5 cm and 3.5 cm ATL resection (n = 207). One RCT found total hippocampectomy to be superior to partial hippocampectomy (n = 70) and one found ATL to be superior to stereotactic radiosurgery (n = 58); and another provided data to show that for Lennox-Gastaut syndrome, no significant differences in seizure outcomes were evident between those treated with resection of the epileptogenic zone and those treated with resection of the epileptogenic zone plus corpus callosotomy (n = 43). We judged evidence from the nine RCTs to be of moderate to very low quality due to lack of information reported about the randomised trial design and the restricted study populations. Of the 16,756 participants included in this review who underwent a surgical procedure, 10,696 (64%) achieved a good outcome from surgery; this ranged across studies from 13.5% to 92.5%. Overall, we found the quality of data in relation to recording of adverse events to be very poor. In total, 120 studies examined between one and eight prognostic factors in univariate analysis. We found the following prognostic factors to be associated with a better post-surgical seizure outcome: abnormal pre-operative MRI, no use of intracranial monitoring, complete surgical resection, presence of mesial temporal sclerosis, concordance of pre-operative MRI and electroencephalography, history of febrile seizures, absence of focal cortical dysplasia/malformation of cortical development, presence of tumour, right-sided resection, and presence of unilateral interictal spikes. We found no evidence that history of head injury, presence of encephalomalacia, presence of vascular malformation, and presence of postoperative discharges were prognostic factors of outcome.Twenty-nine studies reported multi-variable models of prognostic factors, and showed that the direction of association of factors with outcomes was generally the same as that found in univariate analyses. We observed variability in many of our analyses, likely due to small study sizes with unbalanced group sizes and variation in the definition of seizure outcome, the definition of prognostic factors, and the influence of the site of surgery Study design issues and limited information presented in the included studies mean that our results provide limited evidence to aid patient selection for surgery and prediction of likely surgical outcomes. Future research should be of high quality, follow a prospective design, be appropriately powered, and focus on specific issues related to diagnostic tools, the site-specific surgical approach, and other issues such as extent of resection. Researchers should investigate prognostic factors related to the outcome of surgery via multi-variable statistical regression modelling, where variables are selected for modelling according to clinical relevance, and all numerical results of the prognostic models are fully reported. Journal editors should not accept papers for which study authors did not record adverse events from a medical intervention. Researchers have achieved improvements in cancer care over the past three to four decades by answering well-defined questions through the conduct of focused RCTs in a step-wise fashion. The same approach to surgery for epilepsy is required.

We examined evidence from 182 included studies reporting the experience of 16,855 people of all ages. The evidence is current to March 2019. In total, 10,696 people (64% of the total who had surgery in all studies) experienced a good outcome from surgery, defined as freedom from epileptic seizures. Two randomised controlled trials (RCTs) established the superiority of surgery over use of different antiepileptic medications. Seven RCTs compared different types of surgery. Three trials found no difference in seizure outcomes; one removed 2.5cm or 3.5cm of the anterior temporal lobe (ATL - the part of the brain in which the epileptogenic zone is often located) or surgically removed the ATL with or without an additional procedure to sever the nerves that connect the two halves of the brain. The third trial found that completely removing the hippocampus (the part of the brain in which the epileptogenic zone is often located) was superior to removing only part of the hippocampus. A fourth trial showed that removing the ATL was superior to a surgical procedure using radiation therapy, Two trials showed no difference between different types of surgical procedures to remove the ATL or hippocampus and the final trial showed that for Lennox-Gastaut syndrome, results show no significant differences in seizure outcomes between those undergoing resection of the epileptogenic zone and those with resection plus corpus callosotomy. We identified some factors associated with a better outcome from surgery, including a well-defined abnormality on the MRI scan corresponding with what was expected from the description of seizures and EEG findings, complete surgical removal of the lesion, and a history of febrile seizures (seizures associated with fever in a young child) often associated with mesial temporal sclerosis (scarring in the inner portions of the temporal lobe of the brain). More spread out brain abnormalities that might be associated with brain injury or an abnormality of brain development were not associated with a good outcome. The presence of such abnormalities is often associated with a need to embark on more detailed pre-operative investigations including intracranial (inside the skull) EEG monitoring. We would have liked to examine the collective effect of these factors (i.e. the effect on outcome if a person has a history of febrile seizures, brain injury, and an MRI abnormality altogether); however, studies did not report enough information to allow this. Most studies included in this review were of poor quality and had a retrospective design (whereby individuals are recruited after the result of surgery has been recorded, which looks back for the existence of factors related to the results of surgery). Researchers used variable surgical approaches for different sites of the brain, different processes to select candidates for surgery, and different definitions of freedom from seizures after surgery, and they measured these outcomes at varying points. Fewer than half the studies gave details of complications and deaths associated with surgery. We encourage researchers that future studies should have a prospective design (a design whereby individuals are recruited before surgery has taken place, which identifies factors of interest before surgery and follows up with individuals after surgery to record outcomes). Studies should use appropriate statistical methods to examine the collective effect of factors that may predict the outcome of surgery. Study authors should clearly record death during or after surgery, as well as complications and side effects from surgery.

10.1002/14651858.CD010541.pub3

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cochrane-simplification-train-2237

There are no new trials to include in this review update. Previously, four studies with a total of 224 participants were included; one was performed exclusively in children and three in adolescents or adults. One using an antitussive had no extractable pneumonia-specific data. Three different mucolytics (bromhexine, ambroxol, neltenexine) were used in the remaining studies, of which only two had extractable data. They demonstrated no significant difference for the primary outcome of 'not cured or not improved' for mucolytics. A secondary outcome of 'not cured' was reduced (odds ratio (OR) for children 0.36, 95% confidence interval (CI) 0.16 to 0.77; number needed to treat to benefit (NNTB) at day 10 = 5 (95% CI 3 to 16) and OR 0.32 for adults (95% CI 0.13 to 0.75); NNTB at day 10 = 5 (95% CI 3 to 19)). In a post hoc analysis combining data for children and adults, again there was no difference in the primary outcome of 'not cured or not improved' (OR 0.85, 95% CI 0.40 to 1.80) although mucolytics reduced the secondary outcome 'not cured' (OR 0.34, 95% CI 0.19 to 0.60; NNTB 4, 95% CI 3 to 8). The risk of bias was low or unclear. There is insufficient evidence to decide whether OTC medications for cough associated with acute pneumonia are beneficial. Mucolytics may be beneficial but there is insufficient evidence to recommend them as an adjunctive treatment for acute pneumonia. This leaves only theoretical recommendations that OTC medications containing codeine and antihistamines should not be used in young children.

In this review we found four studies with a total of 224 participants that were suitable for inclusion; one was performed exclusively in children and three in adolescents or adults. However, data could only be obtained from two studies; both studies used mucolytics (ambroxol and bromhexine) in conjunction with antibiotics. Combining these two studies, the rate of cure or improvement in cough of people who received mucolytics was similar to those who did not. However, in the secondary analysis, children who received a mucolytic were more likely to be cured of cough (the number needed to treat to benefit (NNTB) at day 10 was 5 for children and 4 for adults). There were no reported increased adverse events in the treatment group. The range of possible adverse events associated with OTC medications for cough is wide and includes minimal adverse events (such as with the use of honey) to serious adverse events, such as altered heart rate patterns, drowsiness and death in young children. The studies included in this review did not report any detectable increase in adverse events. There were no obvious biases in the studies. This review has substantial limitations due to the unavailability of data from studies. Also there are no studies of other common OTC medications used for cough, such as antihistamines and antitussives. Thus, there is insufficient evidence to draw any definitive conclusions on the role of OTC medications taken as an additional treatment for cough associated with acute pneumonia. Mucolytics may be beneficial but the lack of consistent evidence precludes recommending the routine use of mucolytics as an addition in the treatment of troublesome cough associated with pneumonia in children or adults. The evidence is current to January 2014.

10.1002/14651858.CD006088.pub4

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cochrane-simplification-train-2238

In this Cochrane review we identified 19 relevant studies including a total of 1421 patients that examined 16 different intervention comparisons. Of the studies that compared buprenorphine to another drug, 11 studies performed comparative analyses between the randomised groups, and five studies found that buprenorphine was superior to the comparison treatment. Three studies found no differences between buprenorphine and the comparison drug, while another three studies found treatment with buprenorphine to be inferior to the alternative treatment in terms of the side effects profile or patients preference/acceptability. Of the studies that compared different doses or formulations/routes of administration of buprenorphine, pain intensity ratings did not differ significantly between intramuscular buprenorphine and buprenorphine suppository. However, the average severity of dizziness, nausea, vomiting and adverse events as a total were all significantly higher in the intramuscular group relatively to the suppository group (one study). Sublingual buprenorphine was associated with faster onset of pain relief compared to subdermal buprenorphine, with similar duration analgesia and no significant differences in adverse event rates reported between the treatments (one study). In terms of transdermal buprenorphine, two studies found it superior to placebo, whereas a third study found no difference between placebo and different doses of transdermal buprenorphine. The studies that examined different doses of transdermal buprenorphine did not report a clear dose-response relationship. The quality of this evidence base was limited by under-reporting of most bias assessment items (e.g., the patient selection items), by small sample sizes in several included studies, by attrition (with data missing from 8.2% of the enrolled/randomised patients for efficacy and from 14.6% for safety) and by limited or no reporting of the expected outcomes in a number of cases. The evidence for all the outcomes was very low quality. Based on the available evidence, it is difficult to say where buprenorphine fits in the treatment of cancer pain with strong opioids. However, it might be considered to rank as a fourth-line option compared to the more standard therapies of morphine, oxycodone and fentanyl, and even there it would only be suitable for some patients. However, palliative care patients are often heterogeneous and complex, so having a number of analgesics available that can be given differently increases patient and prescriber choice. In particular, the sublingual and injectable routes seemed to have a more definable analgesic effect, whereas the transdermal route studies left more questions.

We searched the literature on 20 Janurary 2015 and found 19 relevant studies with a total of 1421 patients that compared different types of buprenorphine to each other or to other strong pain relief medicines or to placebo. The reported average ages of the patients ranged from 49.1 years to 67.16 years, and the duration of the studies ranged from single dose treatment to six months. Generally, the studies showed that buprenorphine is an effective strong pain relief medicine that in some cases may be slightly better than other strong pain relief medicines. However, the evidence provided by these studies were of very low quality and on the basis of the available evidence, it is still hard to say where buprenorphine fits in in the treatment of cancer pain with strong opioids. All the strong pain relief medicines examined in the studies are also associated with a number of unwanted effects, such as vomiting, constipation and drowsiness.

10.1002/14651858.CD009596.pub4

cochrane-simplification-train-2239

cochrane-simplification-train-2239

We included in this review a total of 17 studies with 1988 participants (evidence current until November 2017). Three studies limited their inclusion to people with intermittent claudication, 12 limited inclusion to people with varying levels of critical limb ischaemia, and two included people with either condition. Study investigators evaluated many different types of gene therapies, using different protocols. Most studies evaluated growth factor-encoding gene therapy, with six studies using vascular endothelial growth factor (VEGF)-encoding genes, four using hepatocyte growth factor (HGF)-encoding genes, and three using fibroblast growth factor (FGF)-encoded genes. Two studies evaluated hypoxia-inducible factor 1-alpha (HIF-1α) gene therapy, one study used a developmental endothelial locus-1 gene therapy, and the final study evaluated a stromal cell-derived factor-1 (SDF-1) gene therapy. Most studies reported outcomes after 12 months of follow-up, but follow-up ranged from three months to two years. Overall risk of bias varied between studies, with many studies not providing sufficient detail for adequate determination of low risk of bias for many domains. Two studies did not utilise a placebo control, leading to risk of performance bias. Several studies reported in previous protocols or in their Methods sections that they would report on certain outcomes for which no data were then reported, increasing risk of reporting bias. All included studies reported sponsorships from corporate entities that led to unclear risk of other bias. The overall quality of evidence ranged from moderate to very low, generally as the result of heterogeneity and imprecision, with few or no studies reporting on outcomes. Evidence suggests no clear differences for the outcomes of amputation-free survival, major amputation, and all-cause mortality between those treated with gene therapy and those not receiving this treatment (all moderate-quality evidence). Low-quality evidence suggests improvement in complete ulcer healing with gene therapy (odds ratio (OR) 2.16, 95% confidence interval (CI) 1.02 to 4.59; P = 0.04). We could not combine data on quality of life and can draw no conclusions at this time regarding this outcome (very low-quality evidence). We included one study in the meta-analysis for ankle brachial index, which showed no clear differences between treatments, but we can draw no overall association (low-quality evidence). We combined in a meta-analysis pain symptom scores as assessed by visual analogue scales from two studies and found no clear differences between treatment groups (very low-quality evidence). We carried out extensive subgroup analyses by PAD classification, dosage schedule, vector type, and gene used but identified no substantial differences. Moderate-quality evidence shows no clear differences in amputation-free survival, major amputation, and all-cause mortality between those treated with gene therapy and those not receiving gene therapy. Some evidence suggests that gene therapy may lead to improved complete ulcer healing, but this outcome needs to be explored with improved reporting of the measure, such as decreased ulcer area in cm², and better description of ulcer types and healing. Further standardised data that are amenable to meta-analysis are needed to evaluate other outcomes such as quality of life, ankle brachial index, symptom scores, and claudication distance.

We included 17 studies that had a total of 1988 participants (evidence current until November 2017). These studies used various types of gene therapy as well as different dosages, some providing single treatments and some repeated treatments. Most of the studies included people with critical limb ischaemia; three studies included people with intermittent claudication. When combining the data, we found no clear differences between people who received gene therapy and those who did not in terms of amputation-free survival (patients who did not have an amputation and did not die), major amputation (above the ankle), or death. We did see improvement in complete ulcer healing in the gene therapy treatment group compared to the control group. Studies show no clear differences in pain symptom scores, but we evaluated only two studies for this outcome. Not enough data are available to show if there was a difference between groups for the measure of blood flow known as the 'ankle brachial index'. We were not able to combine data on quality of life or pain-free walking distances (distances one can walk without experiencing leg pain). Risk of bias of the included studies varied greatly, and this was a concern because studies did not clearly report on their methods nor on follow-up of participants. Most studies used a placebo control, which increases the risk that outcomes may have been different if people knew they were given treatment or control. Corporations that produce the tested treatments sponsored all included trials. The quality of evidence varied from moderate to very low. For amputation-free survival, major amputation, and death, we considered the quality of evidence to be moderate because of differences between studies. For ulcer healing, risk of bias was a matter of concern, and study results were imprecise because few events were reported. The quality of evidence for quality of life was very low because of differences between studies and insufficient information to combine study findings. The quality of evidence for the ankle brachial index was low because only one study with few participants reported this outcome. For pain symptom scores, the quality of evidence was very low because of technical problems within one of the two studies, as well as differences between the two studies and few participants.

10.1002/14651858.CD012058.pub2

cochrane-simplification-train-2240

cochrane-simplification-train-2240

The results of nine randomised controlled trials (N = 482 women) showed that laparoscopic surgery was associated with fewer adverse events of surgery (surgical injury or postoperative complications including fever or infection) (OR 0.3, 95% CI 0.2 to 0.5), less postoperative pain (VAS score WMD -2.4, 95% CI -2.7 to -2.0), greater likelihood of being pain free after two days (OR 7.42, 95% CI 4.86 to 11.33), and fewer days in hospital (WMD -2.88, 95% CI -3.1 to -2.7) than with laparotomy. In one study that reported costs, laparoscopy was associated with a significant reduction in costs compared to laparotomy (WMD - USD 1045, 95% CI -1348 to -742) in 1993. Very high levels of heterogeneity made it inappropriate to pool data on duration of surgery. Three RCTs compared laparoscopy versus minilaparotomy and found that laparoscopy was associated with reduced odds of any adverse event (surgical injury or postoperative complications) (OR 0.10, 95% CI 0 to 0.8) and lower VAS scores for pain (WMD -1.0, 95% CI -1.6 to -0.45). Duration of hospital stay ranged between 1 and 2.2 days, with substantial heterogeneity. In women undergoing surgery for benign ovarian tumours, laparoscopy was associated with a reduction in fever, urinary tract infection, postoperative complications, postoperative pain, number of days in hospital, and total cost. These findings should be interpreted with caution since only a small number of studies were identified. These included a total of only 769 women and not all of the important outcomes were reported in each study.

In the 12 controlled studies identified, laparoscopic surgery was associated with reduced risk of any adverse events from surgery, less pain, and fewer days in the hospital when compared to laparotomy, the traditional surgical technique.There was no difference between the procedures with regard to outcomes of fever, postoperative infections, and tumour recurrence.

10.1002/14651858.CD004751.pub3

cochrane-simplification-train-2241

cochrane-simplification-train-2241

Six RCTs that investigated PUFAs emerged from the search strategy, accounting for 794 randomised patients. PUFAs did not have a significant effect on disease progression at 24 months. Omega-6 fatty acids (11 to 23 g/day linoleic acid) didn't show any benefit in 144 MS patients (RR 1.04, 95% CI 0.66 to 1.63). Linoleic acid (2.9 to 3.4 g/day) had no benefit in 65 chronic progressive MS patients (RR 0.78, 95% CI 0.43 to 1.42). Omega-3 fatty acids had no benefit in 292 relapsing remitting MS patients (RR 0.82, 95% CI 0.65 to 1.03, P = 0.08). Slight potential benefits in relapse outcomes were associated with omega-6 fatty acids in some studies, however these findings were limited by the reduced validity of the endpoints. No judgements about safety or patient-reported outcomes were possible. In general, trial quality was poor. No studies on vitamin supplementation and allergen-free diets were analysed as none met the eligibility criteria, mainly due to lack of clinical outcomes. PUFAs seem to have no major effect on the main clinical outcome in MS (disease progression), but they may tend to reduce the frequency of relapses over two years. However, the data that are available are insufficient to assess a real benefit or harm from PUFA supplementation because of their uncertain quality. Evidence on the possible benefits and risks of vitamin supplementation and antioxidant supplements in MS is lacking. More research is required to assess the effectiveness of dietary interventions in MS.

The authors of this review tried to assess whether changes in dietary habits could favourably influence the prognosis for people with MS. Although a massive amount of data has been published in this area, only six controlled studies on PUFA, comprising a total of 794 patients, met the inclusion criteria in terms of methodological quality for this review. No studies on vitamins and antioxidant supplements were found that met our criteria. No papers on any other proposed dietary interventions for MS were found after extensive searching of the scientific databases. The available data are insufficient to assess any potential benefit or harm that might result from PUFA supplementation. The absence of evidence on PUFA and the extensive lack of data on other supplements is an unfortunate event since 50% to 75% of people with MS do use dietary regimens and supplements.

10.1002/14651858.CD004192.pub3

cochrane-simplification-train-2242

cochrane-simplification-train-2242

Nine randomised trials, including 936 patients, met the inclusion criteria. Methodological quality was considered adequate in only one trial. There was a significant funnel plot asymmetry (regression coefficient=3.37, standard error 1.40, P=0.047). Ten different medicinal herbs were tested in the nine trials. Compared to non-specific treatment or placebo, Fuzheng Jiedu Tang (compound of herbs) showed significantly positive effects on clearance of serum HBsAg, HBeAg, and HBV DNA; Polyporus umbellatus polysaccharide on serum HBeAg and HBV DNA; Phyllanthus amarus on serum HBeAg. Phyllanthus compound and kurorinone showed no significant effect on clearance of serum HBeAg and HBV DNA and on alanine aminotransferase normalisation compared to interferon treatment. There were no significant effects of the other examined herbs. Some Chinese medicinal herbs may work in chronic hepatitis B. However, the evidence is too weak to recommend any single herb. Rigorously designed, randomised, double-blind, placebo-controlled trials are required.

The review of trials found that some of the Chinese medicinal herbs may have a positive effect on the clearance of hepatitis B virus and on the diseased liver. However, the methodological quality of the trials evaluating these herbs was generally poor. Analysis of the identified trials also indicated that trials with positive findings are more likely to be published than trials without significant findings. Further, medicinal herbs may be associated with side effects. Therefore, Chinese medicinal herbs should not be used outside new trials. Testing the herbs in larger, well-designed trials is needed in order to establish the necessary evidence for their use.

10.1002/14651858.CD001940

cochrane-simplification-train-2243

cochrane-simplification-train-2243

We included 10 trials, of which six focused on Parkinson's disease and four on multiple sclerosis. None of the studies reported data on the primary outcome (functional performance). In Parkinson's disease, after pooling two studies, a single session of WBV caused a significant improvement of gait measured using the Timed Up and Go test (TUG) in comparison to standing exercises (mean difference -3.09, 95% confidence interval -5.60 to -0.59; P = 0.02; I2 = 0%). Nevertheless, longer duration of WBV did not show significant results in comparison with physical therapy in body balance or signs and symptoms measured with the Unified Parkinson's Disease Rating Scale (UPDRS). In multiple sclerosis there was no evidence of a short-term or long-term effect of WBV on body balance, gait, muscle performance or quality of life. Adverse events were reported in few trials. In those trials that reported them, the intervention appeared to be safe. There is insufficient evidence of the effect of WBV training on functional performance of neurodegenerative disease patients. Also, there is insufficient evidence regarding its beneficial effects on signs and symptoms of the disease, body balance, gait, muscle strength and quality of life compared to other active physical therapy or passive interventions in Parkinson's disease or multiple sclerosis. More studies assessing other functional tests and accurately assessing safety are needed before a definitive recommendation is established.

Exercise training using vibratory platform (whole body vibration) has been recently introduced as a complementary treatment to rehabilitation.This review identified ten trials performing whole body vibration (WBV) in neurodegenerative diseases: six in Parkinson's disease and four in multiple sclerosis. Diversity in treatments and outcomes measures makes difficult to quantitatively compare the effect of WBV intervention across studies and to assess its efficacy. There is insufficient evidence to determine the potential benefits of WBV training in functional performance according to activities of daily life, body balance, signs and symptoms of disease, muscle performance, and quality of life in patients with neurodegenerative diseases. Adverse events were poorly reported in the included studies, but this kind of training seems to be a safe intervention. These conclusions are based on a small number of studies with a limited methodological quality.

10.1002/14651858.CD009097.pub2

cochrane-simplification-train-2244

cochrane-simplification-train-2244

Two trials with 49 participants were included. One trial had low risk of bias. The other trial had high risk of bias. Hormone replacement had no effect on all-cause mortality (RD 0.00; 95% CI -0.11 to 0.11, I² = 0%) and fractures (RD -0.08; 95% CI -0.24 to 0.07, I² = 0%). Hormone replacement significantly increased adverse events and number of patients having hormone replacement withdrawn due to adverse events (RR 5.26; 95% CI 1.26 to 22.04, I² = 0%). Hormone replacement had no significant effect on lumbar spine bone mineral density (MD 1.25 g/cm² yearֿ¹; 95% CI -0.91 to 3.42, I² = 0%). On the other hand, a significant increase in proximal femur bone mineral density was observed in the control group (MD 2.24 g/cm² yearֿ¹; 95% CI 0.74 to 3.74, I² = 0%). Hormone replacement had no significant effect on liver-related mortality, liver transplantation, or liver-related morbidity. Hormone replacement had no significant effect on serum bilirubin concentration (MD 4.60 µmol/L; 95% CI -3.42 to 12.62, I² = 0%). We did not find evidence to support the use of hormone replacement for women with primary biliary cirrhosis. It seems that hormone replacement is connected with a significant increase in the occurrence of adverse events.

This review assessed the effect of hormone replacement on treatment of osteoporosis in women with primary biliary cirrhosis. We found no evidence of effect of hormone replacement on mortality and fractures in women with primary biliary cirrhosis. It seems that hormone replacement given to women with primary biliary cirrhosis is connected with a significant increase in the occurrence of adverse events compared with placebo or no intervention. Hormone replacement appears to have no effect on the lumbar bone mineral density compared with placebo or no intervention. Hormone replacement may decrease bone mineral density measured at the proximal femur. We did not find evidence to support the use of hormone replacement for osteoporosis in women with primary biliary cirrhosis.

10.1002/14651858.CD009146.pub2

cochrane-simplification-train-2245

cochrane-simplification-train-2245

Five randomised controlled trials (RCTs) with 11,565 participants and three interrupted time series studies (ITSs) with 26.3 data points on average met the criteria. For educational interventions aiming at reducing injury rates among adults the pooled rate ratio after recalculation from effect sizes in three RCTs was 1.02 (95% CI 0.87 to 1.20). For educational interventions aiming at children the pooled rate ratio for injury rates in two RCTs was 1.27 (95% CI 0.51 to 3.16). One ITS study that evaluated the effect of an intervention that included financial incentives decreased the injury level immediately after the intervention with an effect size of -2.68 (95% CI -3.80 to -1.56) but did not have a significant effect on the injury trend over time with an effect size of -0.22 (95% CI -0.47 to 0.03). One ITS study that evaluated the effect of legislation to ban Endosulfan pesticide on fatal pesticide poisonings increased the level of poisonings immediately after the introduction with an effect size of 2.20 (95% CI 0.97 to 3.43) but led to decrease in the trend of poisonings over time with an effect size of -2.15 (95% CI -2.64 to -1.66). One ITS study documented four different regulations aiming to increase the use of rollover protective structures (ROPS) on tractors and their effect on injuries and fatal injuries. The introduction of two different pieces of legislation requiring ROPS on new tractors sold after a certain date was associated with a decrease of fatal injuries over the long term (effect size -0.93 95% CI -1.82 to -0.03). Otherwise the introduction of legislation was associated with an increase of injury rates. Introduction of legislation requiring ROPS on all tractors, old tractors included, was not associated with a decrease but with an increase of injuries and fatal injuries over the long term. The selected studies provided no evidence that educational interventions are effective in decreasing injury rates among agricultural workers. Financial incentives could reduce injury rates. Legislation to ban pesticides could be effective. Legislation expanding the use of safety devices (ROPS) on new tractors was associated with a decrease in fatal injuries.

A systematic literature search was conducted to find studies on interventions to reduce occupational injuries in agriculture. Eight studies were found from over 8600 references. The quality of the relevant studies was assessed and their results extracted. Randomised controlled trial data were combined across studies in a meta-analysis. Interrupted time series studies were reanalysed to assess if there was a change in the level or trend of injuries associated with the intervention. Five randomised controlled trials with 11,565 participants and one interrupted time series study with 14 measurement points used combinations of various educational interventions and financial incentives. Two of these studies concentrated on injury prevention among children or adolescents and the rest dealt with injury prevention among adults. The effect of legislation was evaluated in two interrupted time series studies with on average 32.5 measurement points. One study evaluated regulations to prevent tractor rollover injuries in Sweden and another study evaluated regulation to reduce fatal pesticide poisonings in Sri Lanka. The methodological quality was rated as less than high for all included studies. The studies provided no evidence that the educational interventions had an injury reducing effect. However, insurance premium discounts as a financial incentive decreased injuries claims in one study. Specific legislative mandates expanding the use of Rollover Protective Structures (ROPS) on tractors were not associated with a reduction of injuries in one study. Legislation to ban Endosulfan pesticides was associated with a reduction in fatal poisonings in the long term in another study.

10.1002/14651858.CD006398.pub2

cochrane-simplification-train-2246

cochrane-simplification-train-2246

Three trials involving 126 patients were included, with complete data available for 93 patients. The participants were heterogeneous, none of the three studies examined exactly the same interventions or measured the same outcomes. Only two trials reported mortality data and the summary relative risk for mortality of the intervention was 5.4 (95% CI 0.27 to 107.09). One trial reported increased coagulation times in the transfused group, and reported these patients to have increased rates of rebleeding. None of the studies reported adverse events directly related to RBC transfusion. Methodological deficiencies, including allocation concealment, generation of random sequences and blinding, simply compound the uncertainty surrounding analysis. None of the studies were appropriately powered and in the largest study fewer than half the participants were included in the final analysis. One RCT of restrictive versus liberal RBC transfusion aims to recruit 860 patients but has yet to be completed. There were more deaths and more rebleeding in the transfusion arms of the combined studies, but the small numbers of participants and large volume of missing data limit the significance of the findings. The studies in this review do not provide useful data regarding outcomes following red blood cell transfusion for acute upper gastrointestinal haemorrhage. They appear to exclude large survival benefit. Large, well-concealed RCTs of sufficient power are urgently needed.

This update found no new eligible trials. The original review found three trials investigating the effects of red blood cell transfusion in patients with upper gastrointestinal tract bleeding. There were more deaths recorded in the transfusion arm of the combined studies compared to the control arm. It is by no means clear that transfusion is a surrogate marker for more severe haemorrhage. The deaths were too few and the trials too disparate to draw any firm conclusions regarding the effects of transfusion on mortality. We can only recommend that further, larger studies are done.

10.1002/14651858.CD006613.pub3

cochrane-simplification-train-2247

cochrane-simplification-train-2247

One study with 85 participants met the selection criteria. This trial studied all the absorbent product designs included in this review. Data were presented on all included outcomes. For preventing leakage, for preference and for overall acceptability disposable insert pads are better than disposable menstrual pads which are better than washable pants with integral pad which are better than washable insert pads. There is no strong evidence that either disposables or washables are better for skin health. The disposable insert is the most expensive design and there is no dominant design for cost-effectiveness. There is evidence that some women will prefer alternative designs which are all cheaper than disposable inserts. Although data were available from only one eligible trial the data were sufficiently robust to make recommendations for practice. Disposable insert pads are typically more effective than the other designs considered. However, because they are the most expensive, providing choice of designs (or combinations of designs for different circumstances) is likely to be cost-effective.

This review found only one eligible clinical trial which compared different designs of these products and had been carried out in the last ten years. This trial included all the designs. There is evidence that for leakage prevention, overall acceptability and preference, disposable inserts are better than menstrual pads, which are better than washable pants with integral pad, which are better than washable inserts. There is no clear benefit for skin health using either washable or disposable designs. Most women preferred the disposable insert pad but some preferred the other cheaper designs or would find them acceptable in some situations. Allowing women to choose their preferred design of absorbent product (or combination of different designs for different circumstances) would be more cost-effective and provide better patient satisfaction than provision of disposable insert pads alone.

10.1002/14651858.CD001406.pub2

cochrane-simplification-train-2248

cochrane-simplification-train-2248

From 109 potentially relevant studies only three (104 patients) met our inclusion criteria: Bogie 2007 (46 children), Browne 1997 (29 children) and Nowak 2010 (29 adults). Bogie 2007 investigated the addition of intravenous terbutaline to high dose nebulised albuterol in children with acute severe asthma, requiring intensive care unit (ICU) admission. Browne 1997 investigated the benefit of adding intravenous salbutamol to inhaled salbutamol in children with acute severe asthma in the emergency department. Nowak 2010 investigated addition of IV bedoradrine to standard care (nebulised albuterol, ipratropium and oral corticosteroids) among adults, and was reported as a conference abstract only. There was no significant advantage (OR 0.29; 95%CI 0.06 to 1.38, one trial, 29 adults) for adding IV bedoradrine to standard care (nebulised albuterol, ipratropium and oral corticosteroids) with regard to hospitalisation rates. Various outcome indicators for the length of stay were reported among the trials. Browne 1997 reported a significantly shorter recovery time (in terms of cessation of 30 minute salbutamol) for children in the IV salbutamol with inhaled salbutamol group (four hours) versus the 11.1 hours for the inhaled salbutamol group (P = 0.03). Time to cessation of hourly nebuliser was also significantly shorter (P = 0.02) for the IV plus inhaled salbutamol group (11.5 hours versus 21.2 hours), and they were ready for emergency patient discharge on average 9.7 hours earlier than the inhaled salbutamol group (P < 0.05). In a paediatric ICU study Bogie 2007 reported no significant advantage in length of paediatric ICU admission (hours) for adding IV terbutaline to nebulised albuterol (MD -12.95, 95% CI: -38.74, 12.84). Browne 1997 reported there were only six out of 14 children with a pulmonary index score above six in the IV plus inhaled salbutamol group at two hours compared with 14 of the 15 in the inhaled salbutamol group (P = 0.02) In Browne 1997 there was a higher proportion of tremor in the IV plus inhaled salbutamol group than in the inhaled salbutamol group (P < 0.02). Nowak 2010 did not report any statistically significant adverse effects associated with adding IV bedoradrine to standard care (nebulised albuterol, ipratropium and oral corticosteroids). Troponin levels were elevated in three children in the IV terbutaline + nebulised albuterol group at 12 and 24 hours in Bogie 2007 There is very limited evidence from one study (Browne 1997) to support the use of IV beta2-agonists in children with severe acute asthma with respect to shorter recovery time, and similarly there is limited evidence (again from one study Browne 1997) suggesting benefit with regard to pulmonary index scores; however this advantage needs to be considered carefully in relation to the increased side effects associated with IV beta2-agonists. We identified no significant benefits for adults with severe acute asthma. Until more, adequately powered, high quality clinical trials in this area are conducted it is not possible to form a robust evaluation of the addition of IV beta2-agonists in children or adults with severe acute asthma.

We found three trials involving 104 people (75 children and 29 adults) with acute asthma. There was no significant difference in adults receiving intravenous beta-agonists as well as standard care in the one small trial considering this comparison. We also looked at length of stay in the emergency department. Two reported shorter recovery time or quicker discharge from the emergency department in patients also receiving intravenous beta-agonists. One trial reported that more children experienced tremor if they had received injected beta-agonists whereas another trial, with adults, reported no significant difference in adverse effects. As there are so few trials and so few included patients we cannot be sure about the reliability of these findings. This review found that until more, larger, high quality clinical trials in this area are conducted it is not possible to judge whether there is any enhanced benefit using additional intravenous beta2-agonists in children or adults with severe acute asthma compared with inhaled beta2-agonists alone.

10.1002/14651858.CD010179

cochrane-simplification-train-2249

cochrane-simplification-train-2249

We included 105 studies involving 31,043 participants. This update added 18 studies and removed 28 previously included studies comparing detailed versus simple decision aids. During the 'Risk of bias' assessment, we rated two items (selective reporting and blinding of participants/personnel) as mostly unclear due to inadequate reporting. Twelve of 105 studies were at high risk of bias. With regard to the attributes of the choice made, decision aids increased participants' knowledge (MD 13.27/100; 95% confidence interval (CI) 11.32 to 15.23; 52 studies; N = 13,316; high-quality evidence), accuracy of risk perceptions (RR 2.10; 95% CI 1.66 to 2.66; 17 studies; N = 5096; moderate-quality evidence), and congruency between informed values and care choices (RR 2.06; 95% CI 1.46 to 2.91; 10 studies; N = 4626; low-quality evidence) compared to usual care. Regarding attributes related to the decision-making process and compared to usual care, decision aids decreased decisional conflict related to feeling uninformed (MD −9.28/100; 95% CI −12.20 to −6.36; 27 studies; N = 5707; high-quality evidence), indecision about personal values (MD −8.81/100; 95% CI −11.99 to −5.63; 23 studies; N = 5068; high-quality evidence), and the proportion of people who were passive in decision making (RR 0.68; 95% CI 0.55 to 0.83; 16 studies; N = 3180; moderate-quality evidence). Decision aids reduced the proportion of undecided participants and appeared to have a positive effect on patient-clinician communication. Moreover, those exposed to a decision aid were either equally or more satisfied with their decision, the decision-making process, and/or the preparation for decision making compared to usual care. Decision aids also reduced the number of people choosing major elective invasive surgery in favour of more conservative options (RR 0.86; 95% CI 0.75 to 1.00; 18 studies; N = 3844), but this reduction reached statistical significance only after removing the study on prophylactic mastectomy for breast cancer gene carriers (RR 0.84; 95% CI 0.73 to 0.97; 17 studies; N = 3108). Compared to usual care, decision aids reduced the number of people choosing prostate-specific antigen screening (RR 0.88; 95% CI 0.80 to 0.98; 10 studies; N = 3996) and increased those choosing to start new medications for diabetes (RR 1.65; 95% CI 1.06 to 2.56; 4 studies; N = 447). For other testing and screening choices, mostly there were no differences between decision aids and usual care. The median effect of decision aids on length of consultation was 2.6 minutes longer (24 versus 21; 7.5% increase). The costs of the decision aid group were lower in two studies and similar to usual care in four studies. People receiving decision aids do not appear to differ from those receiving usual care in terms of anxiety, general health outcomes, and condition-specific health outcomes. Studies did not report adverse events associated with the use of decision aids. In subgroup analysis, we compared results for decision aids used in preparation for the consultation versus during the consultation, finding similar improvements in pooled analysis for knowledge and accurate risk perception. For other outcomes, we could not conduct formal subgroup analyses because there were too few studies in each subgroup. Compared to usual care across a wide variety of decision contexts, people exposed to decision aids feel more knowledgeable, better informed, and clearer about their values, and they probably have a more active role in decision making and more accurate risk perceptions. There is growing evidence that decision aids may improve values-congruent choices. There are no adverse effects on health outcomes or satisfaction. New for this updated is evidence indicating improved knowledge and accurate risk perceptions when decision aids are used either within or in preparation for the consultation. Further research is needed on the effects on adherence with the chosen option, cost-effectiveness, and use with lower literacy populations.

For research published up to April 2015, there were 105 studies involving 31,043 people. The decision aids focused on 50 different decisions. The common decisions were about: surgery, screening (e.g. prostate cancer, colon cancer, prenatal), genetic testing, and medication treatments (e.g. diabetes, atrial fibrillation).The decision aids were compared to usual care that may have included general information or no intervention. In the 105 studies, 89 evaluated a patient decision aid used by people in preparation for the visit with the clinician, and 16 evaluated its use during the visit with the clinician. When people use decision aids, they improve their knowledge of the options (high-quality evidence) and feel better informed and more clear about what matters most to them (high-quality evidence). They probably have more accurate expectations of benefits and harms of options (moderate-quality evidence) and probably participate more in decision making (moderate-quality evidence). People who use decision aids may achieve decisions that are consistent with their informed values (evidence is not as strong; more research could change results). People and their clinicians were more likely to talk about the decision when using a decision aid. Decision aids have a variable effect on the option chosen, depending on the choice being considered. Decision aids do not worsen health outcomes, and people using them are not less satisfied. More research is needed to assess if people continue with the option they chose and also to assess what impact decision aids have on healthcare systems.

10.1002/14651858.CD001431.pub5

cochrane-simplification-train-2250

cochrane-simplification-train-2250

We included 11 RCTs with 6750 participants, but only six of these included people with COPD (2469 participants). The others were conducted on elderly and high-risk individuals, some of whom had chronic lung disease. Interventions compared with placebo were inactivated virus injections and live attenuated intranasal virus vaccines. Some studies compared intra-muscular inactivated vaccine and intranasal live attenuated vaccine with intra-muscular inactivated vaccine and intranasal placebo. Studies were conducted in the UK, USA and Thailand. Inactivated vaccine reduced the total number of exacerbations per vaccinated participant compared with those who received placebo (mean difference (MD) –0.37, 95% confidence interval (CI) –0.64 to –0.11; P = 0.006; two RCTs, 180 participants; low quality evidence). This was due to the reduction in 'late' exacerbations, occurring after three or four weeks (MD –0.39, 95% CI –0.61 to –0.18; P = 0.0004; two RCTs, 180 participants; low quality evidence). Both in people with COPD, and in older people (only a minority of whom had COPD), there were significantly more local adverse reactions in people who had received the vaccine, but the effects were generally mild and transient. There was no evidence of an effect of intranasal live attenuated virus when this was added to inactivated intramuscular vaccination. Two studies evaluating mortality for influenza vaccine versus placebo were too small to have detected any effect on mortality. However, a large study (N=2215) noted that there was no difference in mortality when adding live attenuated virus to inactivated virus vaccination, It appeared, from the limited number of RCTs we were able to include, all of which were more than a decade old, that inactivated vaccine reduced exacerbations in people with COPD. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenza. There was a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations. Addition of live attenuated virus to the inactivated vaccine was not shown to confer additional benefit.

We included six studies with 2469 participants with COPD, and a further five studies with 4281 older or high risk participants, a proportion of whom had chronic lung disease. We found some moderate-quality evidence that inactivated influenza vaccine did decrease 'flare ups' of COPD, especially those that are related to the influenza virus itself. The inactivated influenza virus vaccine was given as an injection in the muscle, and was associated with an increase in local side effects (such as pain) at the site of injection, which were short-lived. The inactivated virus vaccine did not cause influenza, or any significant worsening of COPD. Adding a live attenuated virus to the inactivated virus did not add any further protection for the participants. The evidence was of moderate quality. There have been no new trials since 2004. We conducted the last literature search in December 2017.

10.1002/14651858.CD002733.pub3

cochrane-simplification-train-2251

cochrane-simplification-train-2251

We included two studies, involving 319 women. There was no statistically significant difference between the two groups in either of the primary outcomes of caesarean section (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.42 to 2.12) or instrumental delivery (RR 0.88, 95% CI 0.72 to 1.08). Similarly, there were no statistically significant differences between the two groups in any of the secondary outcomes for which data were available. This included Apgar score less than seven at five minutes (RR 3.06, 0.13 to 73.33), admission to neonatal intensive care unit (RR 1.07, 95% CI 0.29 to 3.93), uterine hyperstimulation (RR 1.32, 95% CI 0.97 to 1.80) and postpartum haemorrhage (RR 0.96, 95% CI 0.58, 1.59). There was no statistically significant difference identified between women in spontaneous labour with epidural analgesia who were augmented with oxytocin, compared with those who received placebo. However, due to the limited number of women included in the studies, further research in the form of randomised controlled trials are required.

Data were collected from two randomised studies (involving 319 women) which compared women with epidurals who were given either oxytocin, or a placebo. The rates of operative deliveries were not clearly different between the two groups There were also no significant differences between the other outcomes analysed, such as the Apgar scores of the newborn babies, admissions to the neonatal nursery, rates of post birth haemorrhage or rates of over stimulation of the uterus. Both studies appeared to have a low risk of bias. Overall, there was no significant difference between the rates of operative deliveries in women with epidurals who were given oxytocin compared with those who received the placebo. However, as there were limited data available, in order to fully determine whether augmentation of women with epidurals reduces the rate of operative deliveries and therefore reduces the complications associated, further studies are required.

10.1002/14651858.CD009241.pub3

cochrane-simplification-train-2252

cochrane-simplification-train-2252

Nine trials were identified in the searches and five trials, with a total of 547 participants, met the inclusion criteria. Only one trial reported incidence of pneumococcal infection, and this demonstrated that the polysaccharide pneumococcal vaccine used (PPV14) failed to reduce significantly the risk of infection in children under three years of age, but was associated with only minor adverse events. Three trials of conjugate pneumococcal vaccines found that antibody responses were increased compared to control groups, including those in infants, although clinical outcomes were not measured in these trials. Previous trials have shown that conjugate pneumococcal vaccines are safe and effective in normal healthy individuals, including those under the age of two years. The controlled trials included in this review have demonstrated immunogenicity (the ability to induce the body's immune response, without which there is no protection) of these vaccines, and observational studies in people with sickle cell disease support these findings. We therefore recommend that conjugate pneumococcal vaccines are used in people with sickle cell disease. Randomised trials in people with sickle cell disease will be needed to determine the optimal vaccination regimen when further, potentially more effective vaccines become available. Such trials should measure clinical outcomes of effectiveness. The trials included in this review were published between 1983 and 2003. We have not identified any further relevant trials up to December 2011. We therefore do not plan to update this review until new trials are published.

We searched for trials which compared a polysaccharide or conjugate pneumococcal vaccine schedule with a different schedule or no vaccination in people with sickle cell disease. The review includes five trials with a total of 547 participants. One trial showed that the polysaccharide vaccine did not reduce the risk of infection very much in children younger than three years old, but it was linked with only minor adverse events. Three trials of conjugate vaccines showed increased antibody responses compared to control groups in people of all ages, although clinical outcomes were not measured in these trials. This review did not show if the vaccines prevent infection or decrease death rates. We recommend that conjugate pneumococcal vaccines are used in people with sickle cell disease. Randomised trials will be needed to determine the best vaccination schedule when further, potentially more effective vaccines become available. Such trials should measure clinical outcomes of effectiveness.

10.1002/14651858.CD003885.pub2

cochrane-simplification-train-2253

cochrane-simplification-train-2253

From the 12,966 citations screened, we assessed 26 full-text articles and included five RCTs (643 participants). Low-quality evidence from the meta-analysis performed on two trials using the Oswestry Disability Index (pain-related disability) to compare direct decompression with or without fusion versus multi-modal non-operative care showed no significant differences at six months (mean difference (MD) -3.66, 95% confidence interval (CI) -10.12 to 2.80) and at one year (MD -6.18, 95% CI -15.03 to 2.66). At 24 months, significant differences favoured decompression (MD -4.43, 95% CI -7.91 to -0.96). Low-quality evidence from one small study revealed no difference in pain outcomes between decompression and usual conservative care (bracing and exercise) at three months (risk ratio (RR) 1.38, 95% CI 0.22 to 8.59), four years (RR 7.50, 95% CI 1.00 to 56.48) and 10 years (RR 4.09, 95% CI 0.95 to 17.58). Low-quality evidence from one small study suggested no differences at six weeks in the Oswestry Disability Index for patients treated with minimally invasive mild decompression versus those treated with epidural steroid injections (MD 5.70, 95% CI 0.57 to 10.83; 38 participants). Zurich Claudication Questionnaire (ZCQ) results were better for epidural injection at six weeks (MD -0.60, 95% CI -0.92 to -0.28), and visual analogue scale (VAS) improvements were better in the mild decompression group (MD 2.40, 95% CI 1.92 to 2.88). At 12 weeks, many cross-overs prevented further analysis. Low-quality evidence from a single study including 191 participants favoured the interspinous spacer versus usual conservative treatment at six weeks, six months and one year for symptom severity and physical function. All remaining studies reported complications associated with surgery and conservative side effects of treatment: Two studies reported no major complications in the surgical group, and the other study reported complications in 10% and 24% of participants, including spinous process fracture, coronary ischaemia, respiratory distress, haematoma, stroke, risk of reoperation and death due to pulmonary oedema. We have very little confidence to conclude whether surgical treatment or a conservative approach is better for lumbar spinal stenosis, and we can provide no new recommendations to guide clinical practice. However, it should be noted that the rate of side effects ranged from 10% to 24% in surgical cases, and no side effects were reported for any conservative treatment. No clear benefits were observed with surgery versus non-surgical treatment. These findings suggest that clinicians should be very careful in informing patients about possible treatment options, especially given that conservative treatment options have resulted in no reported side effects. High-quality research is needed to compare surgical versus conservative care for individuals with lumbar spinal stenosis.

Study characteristics: We included five studies that compared surgical versus non-surgical treatment in a total of 643 people with lumbar spinal stenosis. Average age of participants in all studies was over 59 years. Follow-up periods ranged from six weeks to 10 years. Key results: We cannot conclude on the basis of this review whether surgical or non-surgical treatment is better for individuals with lumbar spinal stenosis. Nevertheless, we can report on the high rate of effects reported in three of five surgical groups, ranging from 10% to 24%. No side effects were reported for any of the conservative treatment options. Three studies compared spine surgery versus various types of non-surgical treatment. It is difficult for review authors to draw conclusions from these studies because non-surgical treatments were inadequately described. One study that compared surgery versus bracing and exercise found no differences in pain. Another study compared surgery versus spinal injections and found better physical function with injections, and better pain relief with surgery at six weeks. Still another trial compared surgery with an implanted device versus non-surgical care. This study reported favourable outcomes of surgery for symptoms and physical function. Quality of the evidence: Evidence obtained by comparing surgery versus non-surgical treatment is of low quality. Well-designed studies are needed to examine this problem. In particular, researchers need to do a better job of describing the details of non-surgical treatments.

10.1002/14651858.CD010264.pub2

cochrane-simplification-train-2254

cochrane-simplification-train-2254

We identified three additional trials (613 participants), therefore this update considered 33 studies involving 7296 people with ST of the legs. Treatment included fondaparinux; rivaroxaban; low molecular weight heparin (LMWH); unfractionated heparin (UFH); non-steroidal anti-inflammatory drugs (NSAIDs); compression stockings; and topical, intramuscular, or intravenous treatment to surgical interventions such as thrombectomy or ligation. Only a minority of trials compared treatment with placebo rather than an alternative treatment and many studies were small and of poor quality. Pooling of the data was possible for few outcomes, and none were part of a placebo-controlled trial. In one large, placebo-controlled RCT of 3002 participants, subcutaneous fondaparinux was associated with a significant reduction in symptomatic VTE (risk ratio (RR) 0.15, 95% confidence interval (CI) 0.04 to 0.50; moderate-quality evidence), ST extension (RR 0.08, 95% CI 0.03 to 0.22; moderate-quality evidence), and ST recurrence (RR 0.21, 95% CI 0.08 to 0.54; moderate-quality evidence) relative to placebo. Major bleeding was infrequent in both groups with very wide CIs around risk estimate (RR 0.99, 95% CI 0.06 to 15.86; moderate-quality evidence). In one RCT on 472 high-risk participants with ST, fondaparinux was associated with a non-significant reduction of symptomatic VTE compared to rivaroxaban 10 mg (RR 0.33, 95% CI 0.03 to 3.18; low-quality evidence). There were no major bleeding events in either group (low-quality evidence). In another placebo-controlled trial, both prophylactic and therapeutic doses of LMWH (prophylactic: RR 0.44, 95% CI 0.26 to 0.74; therapeutic: RR 0.46, 95% CI 0.27 to 0.77) and NSAIDs (RR 0.46, 95% CI 0.27 to 0.78) reduced the extension (low-quality evidence) and recurrence of ST (low-quality evidence) in comparison to placebo, with no significant effects on symptomatic VTE (low-quality evidence) or major bleeding (low-quality evidence). Overall, topical treatments improved local symptoms compared with placebo, but no data were provided on the effects on VTE and ST extension. Surgical treatment combined with elastic stockings was associated with a lower VTE rate and ST progression compared with elastic stockings alone. However, the majority of studies that compared different oral treatments, topical treatments, or surgery did not report VTE, ST progression, adverse events, or treatment adverse effects. Prophylactic dose fondaparinux given for 45 days appears to be a valid therapeutic option for ST of the legs for most people. The evidence on topical treatment or surgery is too limited and does not inform clinical practice about the effects of these treatments in terms of VTE. Further research is needed to assess the role of rivaroxaban and other direct oral factor-X or thrombin inhibitors, LMWH, and NSAIDs; the optimal doses and duration of treatment in people at various risk of recurrence; and whether a combination therapy may be more effective than single treatment. Adequately designed and conducted studies are required to clarify the role of topical and surgical treatments.

This update included 33 randomised controlled trials (clinical trials where people are randomly put into one of two or more treatment groups) involving 7296 participants. Treatments included rivaroxaban (a medicine called a direct oral inhibitor of activated factor X), injections of medicines under the skin to prevent blood clotting (e.g. fondaparinux, low molecular weight heparin, or unfractionated heparin), elastic compression stockings, oral non-steroidal anti-inflammatory drugs (NSAIDs; a pain killer medicine), topical treatment (medicine applied to the skin), and surgery. One large study, accounting for half of the participants included in the review, showed that treatment with fondaparinux for 45 days was associated with a significant reduction in symptomatic VTE (where symptoms indicate there is a VTE), ST extension (where the clot moves further up the leg), and recurrence of ST (where clots return) compared to placebo. Major bleeding was infrequent in both groups. In one study in people with ST at high risk of recurrent thromboembolic events, fondaparinux was associated with a non-significant reduction of symptomatic VTE compared to rivaroxaban. There were no major bleeding events in either group. Both low molecular weight heparin and NSAIDs reduced the occurrence of extension or recurrence of ST with no effect on symptomatic VTE or major bleeding. Topical treatments relieved local symptoms but the trials did not report on progression to VTE. Surgical treatment and wearing elastic stockings were associated with a lower rate of VTE and progression of the ST compared with elastic stockings alone. Overall, the quality of evidence was very low for most treatments due to poor study design, imprecision of results, lack of a placebo (non-treated) group and only one study in some comparison. The quality of evidence was low to moderate for comparisons in two placebo-controlled trials. In conclusion, fondaparinux appears to be an adequate treatment for most people with ST. The optimal dose and duration of treatment need to be established in people at high risk as well as people at low risk for recurrent thrombotic events. Further research is needed to assess the role of rivaroxaban and other such medicines, or thrombin, low molecular weight heparin or NSAIDs and to demonstrate the effectiveness, if any, of topical treatment, or surgery in terms of VTE.

10.1002/14651858.CD004982.pub6

cochrane-simplification-train-2255

cochrane-simplification-train-2255

We included in this review nine studies involving a total of 421 participants, 411 of whom were included in the meta-analysis examining short-term effects of music therapy for depression. Concerning primary outcomes, we found moderate-quality evidence of large effects favouring music therapy and TAU over TAU alone for both clinician-rated depressive symptoms (SMD -0.98, 95% CI -1.69 to -0.27, 3 RCTs, 1 CCT, n = 219) and patient-reported depressive symptoms (SMD -0.85, 95% CI -1.37 to -0.34, 3 RCTs, 1 CCT, n = 142). Music therapy was not associated with more or fewer adverse events than TAU. Regarding secondary outcomes, music therapy plus TAU was superior to TAU alone for anxiety and functioning. Music therapy and TAU was not more effective than TAU alone for improved quality of life (SMD 0.32, 95% CI -0.17 to 0.80, P = 0.20, n = 67, low-quality evidence). We found no significant discrepancies in the numbers of participants who left the study early (OR 0.49, 95% CI 0.14 to 1.70, P = 0.26, 5 RCTs, 1 CCT, n = 293, moderate-quality evidence). Findings of the present meta-analysis indicate that music therapy added to TAU provides short-term beneficial effects for people with depression if compared to TAU alone. Additionally, we are uncertain about the effects of music therapy versus psychological therapies on clinician-rated depression (SMD -0.78, 95% CI -2.36 to 0.81, 1 RCT, n = 11, very low-quality evidence), patient-reported depressive symptoms (SMD -1.28, 95% CI -3.75 to 1.02, 4 RCTs, n = 131, low-quality evidence), quality of life (SMD -1.31, 95% CI - 0.36 to 2.99, 1 RCT, n = 11, very low-quality evidence), and leaving the study early (OR 0.17, 95% CI 0.02 to 1.49, 4 RCTs, n = 157, moderate-quality evidence). We found no eligible evidence addressing adverse events, functioning, and anxiety. We do not know whether one form of music therapy is better than another for clinician-rated depressive symptoms (SMD -0.52, 95% CI -1.87 to 0.83, 1 RCT, n = 9, very low-quality evidence), patient-reported depressive symptoms (SMD -0.01, 95% CI -1.33 to 1.30, 1 RCT, n = 9, very low-quality evidence), quality of life (SMD -0.24, 95% CI -1.57 to 1.08, 1 RCT, n = 9, very low-quality evidence), or leaving the study early (OR 0.27, 95% CI 0.01 to 8.46, 1 RCT, n = 10). We found no eligible evidence addressing adverse events, functioning, or anxiety. Findings of the present meta-analysis indicate that music therapy provides short-term beneficial effects for people with depression. Music therapy added to treatment as usual (TAU) seems to improve depressive symptoms compared with TAU alone. Additionally, music therapy plus TAU is not associated with more or fewer adverse events than TAU alone. Music therapy also shows efficacy in decreasing anxiety levels and improving functioning of depressed individuals. Future trials based on adequate design and larger samples of children and adolescents are needed to consolidate our findings. Researchers should consider investigating mechanisms of music therapy for depression. It is important to clearly describe music therapy, TAU, the comparator condition, and the profession of the person who delivers the intervention, for reproducibility and comparison purposes.

We found that music therapy plus treatment as usual is more effective than treatment as usual alone. Music therapy seems to reduce depressive symptoms and anxiety and helps to improve functioning (e.g. maintaining involvement in job, activities, and relationships). We are not sure whether music therapy is better than psychological therapy. We do not know whether one form of music therapy is better than another. The small numbers of identified studies and participants make it hard to be confident about these comparisons. Music therapy for depression is likely to be effective for people in decreasing symptoms of depression and anxiety. Music therapy also helps people to function in their everyday life. However, our findings are not complete and need to be clarified through additional research. Future trials should study depression in children and adolescents, and future trial reports should thoroughly describe music therapy interventions, other interventions, and the person who delivers these interventions.

10.1002/14651858.CD004517.pub3

cochrane-simplification-train-2256

cochrane-simplification-train-2256

We included one randomised cross-over study, enrolling 87 participants, which compared TPD with continuous equilibrating PD (CEPD) for patients with AKI. Sequence generation was adequate while allocation concealment was not reported. Our primary outcomes of mortality and recovery of renal function (complete or partial) were not reported (high risk of selective reporting bias). The results from this one study showed TPD resulted in higher creatinine clearance (CrCl) (MD 1.88 mL/min, 95% CI 0.91 to 2.85) and blood urea nitrogen (BUN) clearance (MD 14.71 mL/min, 95% CI 8.24 to 21.18) than CEPD; was superior to CEPD in the removal of potassium, phosphates and in generating ultrafiltrate; was better tolerated; consumed less time and was less expensive than CEPD. There was greater protein loss with TPD. No adverse events were reported. At present, there is insufficient RCT evidence to enable evaluation of the effect of TPD in patients with AKI. Well-designed and larger RCTs are required to better understand the risks and benefits of TPD for AKI.

We looked for evidence from randomised controlled trials that investigated TPD versus other forms of dialysis for people with AKI. Only one study of enrolling 87 participants was found that compared TPD with continuous equilibrating PD (CEPD). This study showed that TPD produced higher solute clearances in less time with greater protein loss than CEPD, but did not report how well patients recovered kidney function, nor if any people died. There was insufficient evidence to determine if TPD is better or worse than other types of PD for patients with AKI.

10.1002/14651858.CD007016.pub2

cochrane-simplification-train-2257

cochrane-simplification-train-2257

We included two trials with 851 patients that evaluated the efficacy and safety of daclizumab versus placebo for RRMS. We judged them to be at low risk of bias. Due to different time point evaluations and available data on primary studies, we were unable to undertake a meta-analysis. At 24 weeks, the median change was 0 (range -2 to 3) in the interferon beta and placebo group, 0 (-2 to 4) in the interferon beta and low-dose daclizumab group and 0 (-2 to 2) in the interferon beta and high-dose daclizumab group in 230 participants. The proportion of patients who had new clinical relapses were the following: 16 patients (21%) in the interferon beta and high-dose daclizumab group, 19 (24%) in the interferon beta and low-dose daclizumab group and 19 (25%) in the interferon beta and placebo group had relapses (P value = 0.87). At 52 weeks, the changes in Expanded Disability Status Scale (EDSS) from baseline was 0.09 ± 0.71 in placebo group, -0.08 ± 0.52 in low-dose daclizumab group and 0.05 ± 0.61 in high-dose daclizumab group in 621 participants. There was a significant difference between placebo and low-dose daclizumab groups (P value = 0.01), but no significant difference between placebo and high-dose daclizumab groups (P value = 0.49). The proportion of patients with new relapsing MS was significantly reduced in both daclizumab groups (19% in low-dose daclizumab group, 20% in high-dose daclizumab group) compared with placebo group (36%) (P value < 0.0001 and P value = 0.00032, respectively). There was no increased number of patients in any adverse events (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.89 to 1.07) or serious adverse events in daclizumab groups compared with placebo (RR 1.15, 95% CI 0.29 to 4.54). Infections were the most frequent adverse events in treated participants and were resolved with standard therapies. One trial was still ongoing. There was insufficient evidence to determine whether daclizumab was more effective than placebo in patients affected by RRMS in terms of clinical and MRI measures of outcomes. Daclizumab appeared to be relatively well tolerated. Infections were the most frequent adverse events, and were resolved with standard therapies.

To test the efficacy we measured the disability changes and the proportion of patients who had new relapses, while to test the safety we took into account the number of patients who exhibited any type of adverse events. We searched scientific databases for randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment group) comparing daclizumab, alone or with other treatments versus placebo (a pretend treatment). Patients were aged 18 to 65 years with relapsing remitting multiple sclerosis. Evidence is current to May 2013. We found two studies (funded by Facet Biotech/Biogen Idec and Biogen Idec/AbbVie Biotherapeutics Inc), which met our inclusion criteria, with 851 patients, both male and female, aged 18 to 65 years. The results did not provide sufficient evidence on the effectiveness of daclizumab, and further studies are needed. One study is still ongoing. Daclizumab was generally well-tolerated, the most frequent adverse events being infections, which were all resolved with standard therapies. In order to have more clear results, the length of follow-up (where the patients are observed and monitored following treatment) needs to be longer. We considered both studies to be of high quality.

10.1002/14651858.CD008127.pub4

cochrane-simplification-train-2258

cochrane-simplification-train-2258

Two studies, comparing reablement with usual home-care services with 811 participants, met our eligibility criteria for inclusion; we also identified three potentially eligible studies, but findings were not yet available. One included study was conducted in Western Australia with 750 participants (mean age 82.29 years). The second study was conducted in Norway (61 participants; mean age 79 years). We are very uncertain as to the effects of reablement compared with usual care as the evidence was of very low quality for all of the outcomes reported. The main findings were as follows. Functional status: very low quality evidence suggested that reablement may be slightly more effective than usual care in improving function at nine to 12 months (lower scores reflect greater independence; standardised mean difference (SMD) -0.30; 95% confidence interval (CI) -0.53 to -0.06; 2 studies with 249 participants). Adverse events: reablement may make little or no difference to mortality at 12 months' follow-up (RR 0.97; 95% CI 0.74 to 1.29; 2 studies with 811 participants) or rates of unplanned hospital admission at 24 months (RR 0.94; 95% CI 0.85 to 1.03; 1 study with 750 participants). The very low quality evidence also means we are uncertain whether reablement may influence quality of life (SMD -0.23; 95% CI -0.48 to 0.02; 2 trials with 249 participants) or living arrangements (RR 0.92, 95% CI 0.62 to 1.34; 1 study with 750 participants) at time points up to 12 months. People receiving reablement may be slightly less likely to have been approved for a higher level of personal care than people receiving usual care over the 24 months' follow-up (RR 0.87; 95% CI 0.77 to 0.98; 1 trial, 750 participants). Similarly, although there may be a small reduction in total aggregated home and healthcare costs over the 24-month follow-up (reablement: AUD 19,888; usual care: AUD 22,757; 1 trial with 750 participants), we are uncertain about the size and importance of these effects as the results were based on very low quality evidence. Neither study reported user satisfaction with the service. There is considerable uncertainty regarding the effects of reablement as the evidence was of very low quality according to our GRADE ratings. Therefore, the effectiveness of reablement services cannot be supported or refuted until more robust evidence becomes available. There is an urgent need for high quality trials across different health and social care systems due to the increasingly high profile of reablement services in policy and practice in several countries.

The evidence is current to April 2015. The review included two studies, one each from Australia (750 participants) and Norway (61 participants). In both studies, half of the participants received a reablement-based home-care package and half usual home-care provision. The very low quality evidence for all of the results means that we are uncertain about the effects of reablement when compared with usual care. Reablement may help some older adults to improve their abilities to engage in everyday activities (functional status) to a small degree, but may make little or no difference to death rates or admissions to hospital. The findings mean we are also uncertain whether reablement affects quality of life or living arrangements. Reablement may lead to a small decrease in numbers of people needing higher levels of personal care, and may decrease care costs to a small degree, but neither study reported satisfaction of those using the reablement service. While there may be some small positive effects of reablement, the evidence was very low quality, meaning that we are very uncertain about how large or important these effects may be. There is a need for more studies to be conducted in a range of countries and situations before the effectiveness and safety of reablement can be determined with certainty.

10.1002/14651858.CD010825.pub2

cochrane-simplification-train-2259

cochrane-simplification-train-2259

Four studies were included in this review enrolling a total of 123 babies. In one study, persistent hypotension was more common in hydrocortisone treated infants as compared to those who received dopamine as primary treatment for hypotension (RR 8.2, 95% CI 0.47 to 142.6; RD 0.19, 95% CI 0.01 to 0.37). In two studies comparing steroid versus placebo, persistent hypotension (defined as a continuing need for inotrope infusion) was less common in steroid treated infants as compared to controls who received placebo for refractory hypotension (RR 0.35, 95% CI 0.19 to 0.65; RD -0.47, 95% CI - 0.68 to - 0.26; NNT = 2.1, 95% CI 1.47, 3.8). There were no statistically significant effects on any other short or long-term outcome. A further two studies that have only been published in abstract form to date, may be eligible for inclusion in a future update of this review. Hydrocortisone may be as effective as dopamine when used as a primary treatment for hypotension. But the long term safety data on the use of hydrocortisone in this manner is unknown.Steroids are effective in treatment of refractory hypotension in preterm infants without an increase in short term adverse consequences. However, long term safety or benefit data is lacking. With long term benefit or safety data lacking steroids cannot be recommended routinely for the treatment of hypotension in preterm infants.

This review found four small studies that evaluated the effect of steroids on low blood pressure in premature infants. At present, there is insufficient information on which to base recommendations about the value of giving steroids to babies born before term who have low blood pressure.

10.1002/14651858.CD003662.pub4

cochrane-simplification-train-2260

cochrane-simplification-train-2260

We included seven studies (1684 participants) in the review. One study enrolled participants from a residential care facility, and the other six studies from primary care and outpatient clinics. All-cause hospital admission data was available in four studies (556 participants). Participants in the NLT group experienced a lower rate of all-cause hospital admissions (RR 0.80, 95% CI 0.72 to 0.88, high-quality evidence) and fewer hospital admissions related to heart failure (RR 0.51, 95% CI 0.36 to 0.72, moderate-quality evidence) compared to the usual-care group. Six studies (902 participants) examined all-cause mortality. All-cause mortality was also lower in the NLT group (RR 0.66, 95% CI 0.48 to 0.92, moderate-quality evidence) compared to usual care. Approximately 27 deaths could be avoided for every 1000 people receiving NLT of beta-adrenergic blocking agents, ACEIs, and ARBs. Only three studies (370 participants) reported outcomes on all-cause and heart failure-related event-free survival. Participants in the NLT group were more likely to remain event free compared to participants in the usual-care group (RR 0.60, 95% CI 0.46 to 0.77, moderate-quality evidence). Five studies (966 participants) reported on the number of participants reaching target dose of beta-adrenergic blocking agents. This was also higher in the NLT group compared to usual care (RR 1.99, 95% CI 1.61 to 2.47, low-quality evidence). However, there was a substantial degree of heterogeneity in this pooled analysis. We rated the risk of bias in these studies as high mainly due to a lack of clarity regarding incomplete outcome data, lack of reporting on adverse events associated with the intervention, and the inability to blind participants and personnel. Participants in the NLT group reached maximal dose of beta-adrenergic blocking agents in half the time compared with participants in usual care. Two studies reported on adverse events; one of these studies stated there were no adverse events, and the other study found one adverse event but did not specify the type or severity of the adverse event. Participants in the NLT group experienced fewer hospital admissions for any cause and an increase in survival and number of participants reaching target dose within a shorter time period. However, the quality of evidence regarding the proportion of participants reaching target dose was low and should be interpreted with caution. We found high-quality evidence supporting NLT as one strategy that may improve the optimisation of beta-adrenergic blocking agents resulting in a reduction in hospital admissions. Despite evidence of a dose-dependent relationship of beta-adrenergic blocking agents, ACEIs, and ARBs with improving outcomes in patients with HFrEF, the translation of this evidence into clinical practice is poor. NLT is one strategy that facilitates the implementation of this evidence into practice.

We conducted a review of seven randomised controlled trials (1684 participants) comparing nurse titration of beta-adrenergic blocking agents, ACEIs, and ARBs with titration of these medications by a primary care physician. The demographic characteristics of participants within each study were similar. There was an equal number of men and women in four of the studies. The mean age of participants ranged from 59 to 81 years of age. The evidence is current up to December 2014. The review found that participants undergoing titration of these medications were less likely to experience a hospital admission or to die, and more participants reached the maximum dose compared to those participants having these medications titrated by their primary care physician. Approximately 27 deaths could be avoided for every 1000 patients undergoing titration of these medications by nurses under medical supervision or nurse practitioners. There was very little reported data on the titration of ACEIs and ARBs. Two studies reported on adverse events; one of these studies stated there were no adverse events, and the other study found one adverse event but did not specify the type or severity of the adverse event. In conclusion, titration of these medications by nurses under medical supervision or nurse practitioners may improve their up-titration, which may result in an improvement in patient outcomes. We rated the quality of evidence regarding the proportion of participants that reached optimal dose of these medications as low. This indicates uncertainty as to whether the number of participants reaching optimal dose of beta-adrenergic blocking agents was different due to NLT or usual care. We found high-quality evidence that NLT reduced hospitalisations for any cause compared to usual care. This indicates that we are confident that the reduction in all-cause hospitalisations was due to NLT, and further research is unlikely to change this finding.

10.1002/14651858.CD009889.pub2

cochrane-simplification-train-2261

cochrane-simplification-train-2261

Ten studies randomised individuals and trial sizes varied from n=31 to n=549. One study randomised 392 households and enrolled a total of 509 persons with HIV and 1,521 HIV-negative household members. Two ongoing studies were identified. Intensive home-based nursing significantly improved self-reported knowledge of HIV and medications, self-reported adherence and difference in pharmacy drug refill (1 study). Another study, comparing proportion of participants with greater than 90% adherence, found statistically significant differences over time but no significant change in CD4 counts and viral loads. A third study found significant differences in HIV stigma, worry and physical functioning but no differences in depressive symptoms, mood, general health, and overall functioning. Comprehensive case management by trans-professional teams compared to usual care by primary care nurses had no significant difference in quality-of-life after 6-months of follow-up (n=57) and average length of time on service (n=549). Home total parenteral nutrition had no significant impact on overall survival and rate of re-hospitalisation. Two trials comparing computers with brochures/nothing/standard medical care found no significant effect on health status, and decision-making confidence and skill, but a reduction in social isolation after controlling for depression. Two trials evaluating home exercise programmes found opposing results. Home-based safe water systems reduced diarrhea frequency and severity among persons with HIV in Africa. Studies were generally small and very few studies were done in developing countries. There was a lack of studies truly looking at the effect of home based care itself or looking at significant end points (death and progression to AIDS). However, the range of interventions and HBC models evaluated can assist in making evidence-based decisions about HIV care and support.

The objectives of this review was to assess the effects of HBC on morbidity and mortality in those with HIV/AIDS. A comprehensive search for clinical trials of HBC including all forms of treatment, care and support offered in the home was done. Eleven completed and two ongoing studies were identified. Studies were generally small and very few studies were done in developing countries. There was a lack of studies truly looking at the effect of home based care itself or looking at significant end points (death and progression to AIDS). Intensive home-based nursing significantly improved self-reported knowledge of HIV and medications, and self-reported adherence to medication. Another study, comparing proportion of participants with greater than 90% adherence, found statistically significant differences over time but no significant change in CD4 counts and viral loads. A third study found significant differences in HIV stigma, worry and physical functioning but no differences in depressive symptoms, mood, general health, and overall functioning. Comprehensive case management by trans-professional teams compared to usual care by primary care nurses had no significant difference in quality-of-life after 6-months of follow-up and average length of time on service. Home total parenteral nutrition had no significant impact on overall survival and rate of re-hospitalisation. Two trials comparing computers with brochures/nothing/standard medical care found no significant effect on health status, and decision-making confidence and skill, but a reduction in social isolation after controlling for depression. Two trials evaluating home exercise programmes found opposing results. Home-based safe water systems reduced diarrhea frequency and severity among persons with HIV in Africa.

10.1002/14651858.CD005417.pub2

cochrane-simplification-train-2262

cochrane-simplification-train-2262

For the 2013 update, we identified and excluded one new clinical trial. This updated review includes 14 trials, randomizing a total of 8033 women. The unstratified analysis found early intervention with amniotomy and oxytocin to be associated with a modest reduction in the risk of caesarean section; however, the confidence interval (CI) included the null effect (risk ratio (RR) 0.89; 95% CI 0.79 to 1.01; 14 trials; 8033 women). In prevention trials, early augmentation was associated with a modest reduction in the number of caesarean births (RR 0.87; 95% CI 0.77 to 0.99; 11 trials; 7753). A policy of early amniotomy and early oxytocin was associated with a shortened duration of labour (average mean difference (MD) - 1.28 hours; 95% CI -1.97 to -0.59; eight trials; 4816 women). Sensitivity analyses excluding four trials with a full package of active management did not substantially affect the point estimate for risk of caesarean section (RR 0.87; 95% CI 0.73 to 1.05; 10 trials; 5165 women). We found no other significant effects for the other indicators of maternal or neonatal morbidity. In prevention trials, early intervention with amniotomy and oxytocin appears to be associated with a modest reduction in the rate of caesarean section over standard care.

This review includes 14 trials, randomizing a total of 8033 women, and showed that a policy of early routine augmentation for mild delays in labour progress resulted in a modest reduction of the caesarean section rate compared with expectant management. The reduction in caesarean sections was most evident in the 11 trials looking at prevention of abnormal progression, rather than therapy (three trials). In these women, the time from admission to giving birth was also reduced (mean difference 1.3 hours). The trials did not provide sufficient evidence on indicators of maternal or neonatal health, including women’s satisfaction and views on the experience. Documentation of other aspects of care, such as continuous professional support, mobility and positions during labour, was limited as was the degree of contrast between groups. Women in the control group also received oxytocin but often later than in the intervention group. The severity of delay which was sufficient to justify interventions remains to be defined.

10.1002/14651858.CD006794.pub4

cochrane-simplification-train-2263

cochrane-simplification-train-2263

Three studies provided data on the comparison between vitrectomy and observation in eyes with macular hole and visual acuity less than 20/50. Two studies, conducted in the USA and published in 1996 and 1997, used a similar protocol and included participants with stage II macular hole (42 eyes randomised, 36 analysed, number of participants not reported) or participants with stage III/IV hole (129 eyes of 120 participants, 115 eyes in analyses). The third study, conducted in the UK and published in 2004, included 185 eyes of 174 participants with full-thickness macular hole (41 eyes with stage II holes and 74 eyes with stage III/IV holes in analyses). Studies were of good quality for randomisation and allocation concealment, whereas visual acuity measurement was unmasked. At 6 to 12 months, visual acuity was improved by about 1.5 Snellen lines (-0.16 logMAR, 95% confidence intervals -0.23 to -0.09 logMAR, 270 eyes, moderate-quality evidence). The chances of macular hole closure at 6 to 12 months were greatly increased using vitrectomy, yielding an odds ratio of 31.4 (95% confidence intervals 14.9 to 66.3, 265 eyes, high-quality evidence; raw sum data: 76% vitrectomy, 11% observation). Vitrectomy was beneficial both in smaller (stage II) and in larger (stage III/IV) macular holes. The largest study reported that cataract surgery was needed in about half of cases at two years after operation and that retinal detachment occurred in about 5% of operated eyes. Vitrectomy is effective in improving visual acuity, resulting in a moderate visual gain, and in achieving hole closure in people with macular hole. However, these results may not apply to modern surgery due to technological improvements in vitrectomy techniques.

We included three studies, published between 1996 and 2004 and conducted in the USA and the UK, including 270 eyes in analyses, comparing vitrectomy and observation after 6 or 12 months. The evidence is current as of March 2015. Vitrectomy improved visual acuity in participants with macular hole by about 1.5 lines of a standard distance acuity chart. Macular hole closure was much more likely with vitrectomy compared to observation, with mean closure rates of 76% versus 11%, respectively. Cataract surgery was common in operated eyes. In the largest study, retinal detachment occurred in the months following vitrectomy in about 5% of cases. The evidence was of moderate quality, as the visual acuity measurement was unmasked. Vitrectomy is effective in improving visual acuity, resulting in a moderate visual gain, and in achieving hole closure in people with macular hole. However, as vitrectomy technology has improved since the included trials were conducted, with use of a smaller incision and outpatient care, the results of this review may not apply to modern surgery.

10.1002/14651858.CD009080.pub2

cochrane-simplification-train-2264

cochrane-simplification-train-2264

We located two studies (291 participants) for inclusion in this review. The trials were clinically heterogeneous with differences in duration of follow-up, and nasal decontamination regimens. One study compared mupirocin (2% contained in a base of polyethylene glycol 400 and polyethylene glycol 3350) with a placebo in elective cardiac surgery patients; and one study compared Anerdian (iodine 0.45% to 0.57% (W/V), chlorhexidine acetate 0.09% to 0.11% (W/V)) with no treatment also in cardiac surgery patients. The trials reported limited outcome data on SSI, adverse events and secondary outcomes (e.g. S aureus SSI, mortality). Mupirocin compared with placebo This study found no clear difference in SSI risk following use of mupirocin compared with placebo (1 trial, 257 participants); risk ratio (RR) 1.60, 95% confidence interval (CI) 0.79 to 3.25 based on 18/130 events in the mupirocin group and 11/127 in the control group; low-certainty evidence (downgraded twice due to imprecision). Anerdian compared with no treatment It is uncertain whether there is a difference in SSI risk following treatment with Anerdian compared with no treatment (1 trial, 34 participants); RR 0.89, 95% CI 0.06 to 13.08 based on 1/18 events in the Anerdian group and 1/16 in the control group; very low certainty evidence (downgraded twice due to imprecision and once due to risk of bias). There is currently limited rigorous RCT evidence available regarding the clinical effectiveness of nasal decontamination in the prevention of SSI. This limitation is specific to the focused question our review addresses, looking at nasal decontamination as a single intervention in participants undergoing surgery who are known S aureus carriers. We were only able to identify two studies that met the inclusion criteria for this review and one of these was very small and poorly reported. The potential benefits and harms of using decontamination for the prevention of SSI in this group of people remain uncertain.

In September 2016 we searched for randomised controlled trials (RCTs) involving nasal decontamination for preventing SSI. We included two studies with 291 participants, all adults undergoing cardiac surgery. The anti-bacterial products used for cleaning the nose were mupirocin (antibiotic cream) and Anerdian (disinfectant solution). It is unclear whether nasal decontamination makes a difference to the rate of SSI in people carrying S aureus bacteria. S aureus SSI was reported in only one trial and the results do not allow us to be certain about differences in infection rates. Some participants in the Anerdian study reported side effects such as itching around the nose, but these were not serious. Mortality was low where reported (one death was directly related to S aureus infection). The two studies we found did not have many participants and the results were inconclusive. The Anerdian study report did not provide information about how the trial was conducted and this makes it difficult to be sure if it was at risk of bias. The mupirocin study was of better quality and at low risk of bias; but the small number of participants and limited effects affect the quality of the results. Evidence of the potential benefits and harms of using nasal decontamination for the prevention of SSI is currently of low to very low certainty. Larger, better-reported RCTs are needed to assess the clinical effectiveness of this treatment. This plain language summary is up to date as of September 2016.

10.1002/14651858.CD012462.pub2

cochrane-simplification-train-2265

cochrane-simplification-train-2265

Forty-five cluster-RCTs, two quasi-RCTs, and eight CBA studies, including over 84,000 participants, met the inclusion criteria. Most included studies were conducted in low- or middle-income countries (LMICs) (50 studies) with unimproved water sources (30 studies) and unimproved or unclear sanitation (34 studies). The primary outcome in most studies was self-reported diarrhoea, which is at high risk of bias due to the lack of blinding in over 80% of the included studies. Source-based water quality improvements There is currently insufficient evidence to know if source-based improvements such as protected wells, communal tap stands, or chlorination/filtration of community sources consistently reduce diarrhoea (one cluster-RCT, five CBA studies, very low quality evidence). We found no studies evaluating reliable piped-in water supplies delivered to households. Point-of-use water quality interventions On average, distributing water disinfection products for use at the household level may reduce diarrhoea by around one quarter (Home chlorination products: RR 0.77, 95% CI 0.65 to 0.91; 14 trials, 30,746 participants, low quality evidence; flocculation and disinfection sachets: RR 0.69, 95% CI 0.58 to 0.82, four trials, 11,788 participants, moderate quality evidence). However, there was substantial heterogeneity in the size of the effect estimates between individual studies. Point-of-use filtration systems probably reduce diarrhoea by around a half (RR 0.48, 95% CI 0.38 to 0.59, 18 trials, 15,582 participants, moderate quality evidence). Important reductions in diarrhoea episodes were shown with ceramic filters, biosand systems and LifeStraw® filters; (Ceramic: RR 0.39, 95% CI 0.28 to 0.53; eight trials, 5763 participants, moderate quality evidence; Biosand: RR 0.47, 95% CI 0.39 to 0.57; four trials, 5504 participants, moderate quality evidence; LifeStraw®: RR 0.69, 95% CI 0.51 to 0.93; three trials, 3259 participants, low quality evidence). Plumbed in filters have only been evaluated in high-income settings (RR 0.81, 95% CI 0.71 to 0.94, three trials, 1056 participants, fixed effects model). In low-income settings, solar water disinfection (SODIS) by distribution of plastic bottles with instructions to leave filled bottles in direct sunlight for at least six hours before drinking probably reduces diarrhoea by around a third (RR 0.62, 95% CI 0.42 to 0.94; four trials, 3460 participants, moderate quality evidence). In subgroup analyses, larger effects were seen in trials with higher adherence, and trials that provided a safe storage container. In most cases, the reduction in diarrhoea shown in the studies was evident in settings with improved and unimproved water sources and sanitation. Interventions that address the microbial contamination of water at the point-of-use may be important interim measures to improve drinking water quality until homes can be reached with safe, reliable, piped-in water connections. The average estimates of effect for each individual point-of-use intervention generally show important effects. Comparisons between these estimates do not provide evidence of superiority of one intervention over another, as such comparisons are confounded by the study setting, design, and population. Further studies assessing the effects of household connections and chlorination at the point of delivery will help improve our knowledge base. As evidence suggests effectiveness improves with adherence, studies assessing programmatic approaches to optimising coverage and long-term utilization of these interventions among vulnerable populations could also help strategies to improve health outcomes.

This Cochrane Review summarizes trials evaluating different interventions to improve water quality and prevent diarrhoea. After searching for relevant trials up to 11 November 2014, we included 55 studies enrolling over 84,000 participants. Most included studies were conducted in low- or middle-income countries (LMICs) (50 studies), with unimproved water sources (30 studies), and unimproved or unclear sanitation (34 studies). What causes diarrhoea and what water quality interventions might prevent diarrhoea? Diarrhoea is a major cause of death and disease, especially among young children in low-income countries where the most common causes are faecally contaminated water and food, or poor hygiene practices. In remote and low-income settings, source-based water quality improvement may include providing protected groundwater (springs, wells, and bore holes) or harvested rainwater as an alternative to surface sources (rivers and lakes). Alternatively water may be treated at the point-of-use in people's homes by boiling, chlorination, flocculation, filtration, or solar disinfection. These point-of-use interventions have the potential to overcome both contaminated sources and recontamination of safe water in the home. What the research says There is currently insufficient evidence to know if source-based improvements in water supplies, such as protected wells and communal tap stands or treatment of communal supplies, consistently reduce diarrhoea in low-income settings (very low quality evidence). We found no trials evaluating reliable piped-in water supplies to people's homes. On average, distributing disinfection products for use in the home may reduce diarrhoea by around one quarter in the case of chlorine products (low quality evidence), and around a third in the case of flocculation and disinfection sachets (moderate quality evidence). Water filtration at home probably reduces diarrhoea by around a half (moderate quality evidence), and effects were consistently seen with ceramic filters (moderate quality evidence), biosand systems (moderate quality evidence) and LifeStraw® filters (low quality evidence). Plumbed-in filtration has only been evaluated in high-income settings (low quality evidence). In low-income settings, distributing plastic bottles with instructions to leave filled bottles in direct sunlight for at least six hours before drinking probably reduces diarrhoea by around a third (moderate quality evidence). Research assessing the effects of household connections and chlorination at the point of delivery will help improve our knowledge base. Evidence indicates the more people use the various interventions for improving water quality, the larger the effects, so research into practical approaches to increase coverage and help assure long term use of them in poor groups will help improve impact.

10.1002/14651858.CD004794.pub3

cochrane-simplification-train-2266

cochrane-simplification-train-2266

Three studies met the inclusion criteria. These included one placebo-controlled trial (942 patients) and two add-on placebo-controlled trials, i.e. one plus glatiramer acetate (110 patients) and the second plus interferon beta-1a (1171 patients). This review assessed the efficacy, tolerability and safety of NTZ in patients with RRMS. Data was conclusive with respect to efficacy and tolerability, but not safety. As far as efficacy is concerned, the results showed statistically significant evidence in favour of NTZ for all the primary outcomes and for the secondary ones where data was available. NTZ reduced the risk of experiencing at least one new exacerbation at 2 years by about 40% and of experiencing progression at 2 years by about 25% as compared to a control group. MRI parameters showed statistical evidence in favour of participants receiving NTZ. Infusion reactions, anxiety, sinus congestion, lower limb swelling, rigors, vaginitis and menstrual disorders were reported as adverse events (AEs) more frequently after NTZ treatment. In this review NTZ was found to be well tolerated over a follow-up period of two years: the number of patients experiencing at least one AE (including severe and serious AEs) during this period did not differ between NTZ-treated patients and controls. Safety concerns have been raised about Progressive Multifocal Leukoencephalopathy (PML). In the trials included in this review, two cases of PML were encountered: one in a patient who had received 29 doses of NTZ and a second fatal case of PML in another patient after 37 doses of NTZ. Our protocol was insufficient to evaluate PML risk as well as other rare and long-term adverse events such as cancers and other opportunistic infections, which are very important issues in considering the risk/benefit ratio of NTZ. Although one trial did not contribute to efficacy results due to its duration, we found robust evidence in favour of a reduction in relapses and disability at 2 years in RRMS patients treated with NTZ. The drug was well tolerated. There are current significant safety concerns due to reporting of an increasing number of PML cases in patients treated with NTZ. This review was unable to provide an up-to-date systematic assessment of the risk due to the maximum 2 year-duration of the trials included. An independent systematic review of the safety profile of NTZ is warranted. NTZ should be used only by skilled neurologists in MS centres under surveillance programs. All the data in this review came from trials supported by the Pharmaceutical Industry. In agreement with the Cochrane Collaboration policy, this may be considered a potential source of bias.

The Authors of this review evaluated the efficacy, tolerability and safety of NTZ in patients with RRMS. Among the pertinent literature, 3 studies met the inclusion criteria of methodological quality, comprising a total of 2223 participants. The results show that NTZ treatment reduces the number of patients who experienced relapses and the number of patients who progressed at 2 years. Also Magnetic Resonance scans show evidence of a beneficial effect of NTZ on disease activity. Although information on adverse events (AEs) was limited, as most participants were followed up for 2 years only, infusion reactions, anxiety, sinus congestion, lower limb swelling, rigors, vaginal inflammation and menstrual disorders were found to be more frequent after NTZ treatment. However, the number of patients experiencing at least one AE (including severe or serious AEs) did not differ between NTZ and control groups. On the contrary, significant safety concerns have been raised regarding Progressive Multifocal Leukoencephalopathy (PML), a rare and often fatal viral disease characterized by damage to the white matter of the brain. In the studies included in this review, PML was reported in 2 patients treated with NTZ for more than 2 years. However, our protocol was insufficient to evaluate PML risk as well as other potential rare and long-term AEs (e.g. cancers and other infections) which are important issues in considering the risk/benefit ratio of NTZ. An independent systematic review of the safety profile of NTZ is warranted. NTZ should be used only by skilled neurologists in MS centres under surveillance programs. All the data in this review came from studies supported by the Pharmaceutical Industry. In agreement with the Cochrane Collaboration policy, this may be considered a potential source of bias.

10.1002/14651858.CD007621.pub2

cochrane-simplification-train-2267

cochrane-simplification-train-2267

We included three studies with 1853 participants who had undergone surgical removal of impacted wisdom teeth, hip replacement, or hysterectomy. The overall risk of bias across the three included studies was low, with unclear risk of bias in relation to the size of the three studies. Two studies did not report all our prespecified outcomes, which limited the analyses we could do. The proportion of participants achieving at least 50% pain relief over six hours with dexketoprofen 25 mg plus tramadol 75 mg was 66%, compared to 32% with placebo, giving an NNT of 3.0 (95% CI 2.5 to 3.7) (RR 2.1 (95% CI 1.7 to 2.4); 748 participants; 3 studies) (moderate quality evidence). The response rate with dexketoprofen 25 mg alone was 53% (RR 1.3 (95% CI 1.1 to 1.4); 744 participants; 3 studies) and with tramadol alone was 45% (RR 1.5 (95% CI 1.3 to 1.7); 741 participants; 3 studies) (moderate quality evidence). We downgraded the evidence because of some inconsistency in the results. The median time to use of rescue medication could not be estimated exactly, but was probably eight hours or more, indicating a long duration of effect (moderate quality evidence). We downgraded the evidence because it was not possible to estimate the effect exactly in the two multiple dose studies, resulting in imprecision. Fewer participants used rescue medication with higher doses of active treatment (summary statistic not calculated; 123 participants; 1 study) (very low quality evidence). We downgraded the evidence because the data came from a single study with few participants and events. Adverse events and serious adverse events were not reported consistently for the single dose phase of the studies. In the single dose study, 11% of participants experienced adverse events with dexketoprofen 25 mg plus tramadol 75 mg, which were mostly mild or moderate nausea, vomiting, or dizziness, and typical with these medicines. Rates were lower with placebo and lower doses (very low quality evidence). We downgraded the evidence because the data came from a single study with few participants and events. Information on multiple dosing over three and five days supported a low event rate with the combination. Overall, rates were generally low in all treatment arms, as they were for withdrawals for adverse events or other reasons. A single oral dose of dexketoprofen 25 mg plus tramadol 75 mg provided good levels of pain relief with long duration of action to more people than placebo or the same dose of dexketoprofen or tramadol alone. The magnitude of the effect was similar to other good analgesics. Adverse event rates were low. There is modest uncertainty about the precision of the point estimate for efficacy, but the NNT of 3 is consistent with other analgesics considered effective and commonly used.

In May 2016, we found three studies involving 1853 people. The main comparison was between the fixed-dose of dexketoprofen 25 mg plus tramadol 75 mg and placebo (a dummy treatment). The studies tested single doses after wisdom tooth extraction, hip replacement operations, and gynaecological (female reproductive system) operations. Studies included adults over a range of ages, and 7 out of 10 participants were women. The main outcome was the number of participants having at least half of the maximum possible pain relief over the first six hours after taking the tablets. All three studies reported the main outcome for dexketoprofen 25 mg plus tramadol 75 mg. There were 748 participants in the comparison with placebo. About 7 in 10 people achieved this outcome with dexketoprofen 25 mg plus tramadol 75 mg, compared with 3 in 10 with placebo. The combination was significantly better than placebo, and better than either dexketoprofen or tramadol alone. The pain relief lasted a long time, probably eight hours or more, but the exact duration could not be determined. Fewer people needed to take additional painkillers with the combination treatment than with placebo. About 1 in 10 people had side effects with dexketoprofen 25 mg plus tramadol 75 mg. These were mostly mild or moderate nausea (feeling sick), vomiting (being sick), and dizziness, which are typical with these medicines. Serious side effects were uncommon. Few people dropped out of the studies. We judged the quality of the evidence as moderate for the painkilling effect of dexketoprofen 25 mg plus tramadol 75 mg. For side effects we judged the quality of the evidence about a single dose as very low because there were so few participants and events, but we judged it as moderate when we included evidence from the three- and five-day studies. Moderate quality evidence means that more information might change our estimate of the effect. Very low quality evidence means that we are very uncertain about the results.

10.1002/14651858.CD012232.pub2

cochrane-simplification-train-2268

cochrane-simplification-train-2268

No new studies were included for this update. Seven studies with a combined total of 802 participants were included in this review. No significant difference was observed between heparin treatment and control groups for pain-free walking distance or maximum walking distance at the end of treatment. There were no data to indicate that LMWHs benefit walking distance. Revascularisation or amputation-free survival rates were reported in one study only with a five year follow-up. No study reported a significant effect on overall mortality or cardiovascular events and the pooled odds ratios were not significant for these outcomes either. Major and minor bleeding events were significantly more frequent in the group treated with oral anticoagulants compared to control, with a non-significant increase in fatal bleeding events. No major bleeding events were reported in the study evaluating heparin, while a non-significant increase in minor bleeding events was reported. The benefit of heparin, LMWHs and oral anticoagulants for treatment of intermittent claudication has not been established while an increased risk of major bleeding events has been observed, especially with oral anticoagulants. There is no clear evidence to support the use of anticoagulants for intermittent claudication at this stage.

No new studies were included for this update. Seven studies with 802 participants were included in this review. The review of trials found that the benefit of heparin, LMWHs and oral anticoagulants for treatment of intermittent claudication has not been established while an increased risk of major bleeding events has been observed, especially with oral anticoagulants. There is no clear evidence to support the use of anticoagulants for intermittent claudication at this stage. More research is needed.

10.1002/14651858.CD001999.pub2

cochrane-simplification-train-2269

cochrane-simplification-train-2269

Twenty small trials (1239 people with neck pain) containing 38 comparisons were included. Analysis was limited by trials of varied quality, heterogeneous treatment subtypes and conflicting results. The main findings for reduction of neck pain by treatment with electrotherapeutic modalities were as follows. Very low quality evidence determined that pulsed electromagnetic field therapy (PEMF) and repetitive magnetic stimulation (rMS) were more effective than placebo, while transcutaneous electrical nerve stimulation (TENS) showed inconsistent results. Very low quality evidence determined that PEMF, rMS and TENS were more effective than placebo. Low quality evidence (1 trial, 52 participants) determined that permanent magnets (necklace) were no more effective than placebo (standardized mean difference (SMD) 0.27, 95% CI -0.27 to 0.82, random-effects model). Very low quality evidence showed that modulated galvanic current, iontophoresis and electric muscle stimulation (EMS) were not more effective than placebo. There were four trials that reported on other outcomes such as function and global perceived effects, but none of the effects were of clinical importance. When TENS, iontophoresis and PEMF were compared to another treatment, very low quality evidence prevented us from suggesting any recommendations. No adverse side effects were reported in any of the included studies. We cannot make any definite statements on the efficacy and clinical usefulness of electrotherapy modalities for neck pain. Since the evidence is of low or very low quality, we are uncertain about the estimate of the effect. Further research is very likely to change both the estimate of effect and our confidence in the results. Current evidence for PEMF, rMS, and TENS shows that these modalities might be more effective than placebo. When compared to other interventions the quality of evidence was very low thus preventing further recommendations. Funding bias should be considered, especially in PEMF studies. Galvanic current, iontophoresis, EMS, and a static magnetic field did not reduce pain or disability. Future trials on these interventions should have larger patient samples, include more precise standardization, and detail treatment characteristics.

This updated review included 20 small trials (N = 1239). We included adults (> 18 years old) with acute whiplash or non-specific neck pain as well as chronic neck pain including degenerative changes, myofascial pain or headaches that stem from the neck. No index for severity of the disorders could be specified. The evidence was current to August 2012. The results of the trials could not be pooled because they examined different populations, types and doses of electrotherapy and comparison treatments, and measured slightly different outcomes. We cannot make any definitive statements about the efficacy of electrotherapy for neck pain because of the low or very low quality of the evidence for each outcome, which in most cases was based on the results of only one trial. For patients with acute neck pain, TENS possibly relieved pain better than electrical muscle stimulation, not as well as exercise and infrared light, and as well as manual therapy and ultrasound. There was no additional benefit when added to infrared light, hot packs and exercise, physiotherapy, or a combination of a neck collar, exercise and pain medication. For patients with acute whiplash, iontophoresis was no more effective than no treatment, interferential current, or a combination of traction, exercise and massage for relieving neck pain with headache. For patients with chronic neck pain, TENS possibly relieved pain better than placebo and electrical muscle stimulation, not as well as exercise and infrared light, and possibly as well as manual therapy and ultrasound. Magnetic necklaces were no more effective than placebo for relieving pain; and there was no additional benefit when electrical muscle stimulation was added to either mobilisation or manipulation. For patients with myofascial neck pain, TENS, FREMS (FREquency Modulated Neural Stimulation, a variation of TENS) and repetitive magnetic stimulation seemed to relieve pain better than placebo. About 70% of the trials were poorly conducted studies. The trials were very small, with a range of 16 to 336 participants. The data were sparse and imprecise, which suggests that results cannot be generalized to the broader population and contributes to the reduction in the quality of the evidence. Therefore, further research is very likely to change the results and our confidence in the results.

10.1002/14651858.CD004251.pub5

cochrane-simplification-train-2270

cochrane-simplification-train-2270

Four cross-over studies, published between 1968 and 1982, involving 121 patients, and four different NSAIDs were included. The generation of the allocation sequence and the use of methods to conceal the allocation were not described in any of the studies. The studies were double-blind but it was not clear whether the blinding was effective. Methods for collecting adverse effects were not described. The NSAIDs were preferred more often than paracetamol by the patients or the investigator. In the largest trial, 20 out of 54 patients (37%) preferred ibuprofen and 7 out of 54 (13%) paracetamol. Investigators preference (as established by joint tenderness, grip strength and joint circumference) was 17 out of 35 for diclofenac versus 5 out of 35 for paracetamol in another trial. However, because of the weaknesses in the trials, no firm conclusion can be drawn. When considering the trade off between the benefits and harms of non-steroidal anti-inflammatory drugs and paracetamol/acetaminophen, it is not known whether one is better than the other for rheumatoid arthritis. But people with rheumatoid arthritis and the researchers in the study did prefer non-steroidal anti-inflammatory drugs more than acetaminophen/paracetamol. There is a need for a large trial, with appropriate randomisation, double-blinding, test of the success of the blinding, and with explicit methods to measure and analyse pain and adverse effects.

This Cochrane review found only four old and small trials of poor quality that have compared the two types of drugs. There were a total of 121 patients in the four trials. In each trial, the patients tried both types of drugs, one after the other, in different periods of the trial. In the largest trial, of 54 patients, where each drug was tested twice, 20 patients preferred ibuprofen on both occasions, and 7 paracetamol. In the trials, each drug was used for only 4-7 days and side effects from the drugs were poorly reported. It is therefore not clear whether NSAIDs are better than paracetamol.

10.1002/14651858.CD003789.pub2

cochrane-simplification-train-2271

cochrane-simplification-train-2271

The review included 27 RCTs involving 1803 children. Of these, six were multi-arm and one was also a cross-over study. Most studies were small, with numbers randomised ranging from 16 to 202. A total of 19 studies were at high risk of bias for at least one domain. Few studies reported data suitable for pooling due to heterogeneity in interventions, outcomes and measurements. Individual conservative interventions (lifestyle, behavioural or physical) versus no treatment Transcutaneous electrical nerve stimulation (TENS) versus sham (placebo) TENS. More children receiving active TENS may achieve continence (risk ratio (RR) 4.89, 95% confidence interval (CI) 1.68 to 14.21; 3 studies; n = 93; low-certainty evidence). One individual conservative intervention versus another individual or combined conservative intervention Pelvic floor muscle training (PFMT) with urotherapy versus urotherapy alone. We are uncertain whether more children receiving PFMT with urotherapy achieve continence (RR 2.36, 95% CI 0.65 to 8.53, 95% CI 25 to 100; 3 studies; n = 91; very low-certainty evidence). Voiding education with uroflowmetry feedback and urotherapy versus urotherapy alone. Slightly more children receiving voiding education with uroflow feedback and urotherapy may achieve continence (RR 1.13, 95% CI 0.87 to 1.45; 3 studies; n = 151; low-certainty evidence). Urotherapy with timer watch versus urotherapy alone. We are uncertain whether urotherapy plus timer watch increases the number of children achieving continence compared to urotherapy alone (RR 1.42, 95% CI 1.12 to 1.80; 1 study; n = 58; very low-certainty evidence). Combined conservative interventions versus other combined conservative interventions TENS and standard urotherapy versus PFMT with electromyographic biofeedback and standard urotherapy. We are uncertain whether there is any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 1.11, 95% CI 0.73 to 1.68; 1 study; n = 78; very low-certainty evidence). PFMT with electromyography biofeedback and standard urotherapy versus PFMT without feedback but with standard urotherapy. We are uncertain whether there is any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 1.05, 95% CI 0.72 to 1.52; 1 study; n = 41; very low-certainty evidence). Individual conservative interventions versus non-conservative interventions (pharmacological or invasive, combined or not with any conservative interventions) PFMT versus anticholinergics. We are uncertain whether more children receiving PFMT than anticholinergics achieve continence (RR 1.92, 95% CI 1.17 to 3.15; equivalent to an increase from 33 to 64 per 100 children; 2 studies; n = 86; very low-certainty evidence). TENS versus anticholinergics. We are uncertain whether there was any evidence of a difference between treatment groups in the proportions of children achieving continence (RR 0.81, 95% CI 0.05 to 12.50; 2 studies; n = 72; very low-certainty evidence). Combined conservative interventions versus non-conservative interventions (pharmacological or invasive, combined or not with any conservative interventions) Voiding education with uroflowmetry feedback versus anticholinergics. We are uncertain whether there was any evidence of a difference between treatment groups in the proportion of children achieving continence (RR 1.02, 95% CI 0.58 to 1.78; 1 study; n = 64; very low-certainty evidence). The review found little reliable evidence that can help affected children, their carers and the clinicians working with them to make evidence-based treatment decisions. In this scenario, the clinical experience of individual clinicians and the support of carers may be the most valuable resources. More well-designed research, with well-defined interventions and consistent outcome measurement, is needed.

The review identified 27 studies involving 1803 children. Twelve studies declared funding from outside sources. One of these was funded by Astellas Pharma, while another study was provided with special batches of placebo and medication free of charge, as well as materials for pad tests free of charge from another company. Cochrane Reviews assess the 'certainty' or reliability of the evidence using standardised methods that consider the way studies were designed, conducted and reported, differences between studies or populations, and the combined results of studies. Most of the studies identified for this review were small and many were poorly designed and not reported clearly. Most of the evidence was considered to be of very low certainty, meaning that little can be said with any certainty about the effectiveness of treatments. Transcutaneous electrical nerve stimulation (TENS) may be more effective than no treatment for ending or reducing daytime wetting. We are uncertain whether urotherapy (behavioural programmes in which children - and sometimes carers - are taught about how the bladder works, proper toileting postures and methods, scheduled toileting, and planning what and how much to drink) is more effective when supplemented with PFMT, voiding education with feedback, or watches with alarms set to remind children when to go to the toilet. We are uncertain whether feedback that shows children how their muscles are working or how their bladder is emptying improves the effectiveness of TENS with urotherapy compared to PFMT plus feedback and urotherapy. We are also uncertain whether PFMT and urotherapy plus feedback improves the effectiveness of PFMT and urotherapy alone. We are uncertain whether pelvic floor muscle training (PFMT) or TENS are more effective than anticholinergics (drugs that can reduce signals from the brain that cause the bladder to contract and empty). We are uncertain whether voiding education plus uroflowmetry (a test to measure the volume of urine) and feedback increases the number of continent children compared to anticholinergics. No serious adverse events were reported that were considered to be related to study treatments. Most non-serious adverse events and side effects were mild or moderate in severity and were in children receiving pharmaceutical interventions. These included common pharmaceutical side effects such as nausea, abdominal pain, dry mouth, drowsiness and headache. There is a lack of good-quality research evidence that can help children, their carers and doctors and nurses to make decisions about treatments. More well-designed research may provide much needed evidence about the effectiveness of promising interventions in children with daytime urinary incontinence, such as TENS, PFMT and timers on watches (or mobile phones) to remind children about toileting schedules. However, it is hoped that this review will draw attention to the need for research into effective treatments for daytime wetting in children.

10.1002/14651858.CD012367.pub2

cochrane-simplification-train-2272

cochrane-simplification-train-2272

The network meta-analysis included 196 trials (135,559 women) involving seven uterotonic agents and placebo or no treatment, conducted across 53 countries (including high-, middle- and low-income countries). Most trials were performed in a hospital setting (187/196, 95.4%) with women undergoing a vaginal birth (71.5%, 140/196). Relative effects from the network meta-analysis suggested that all agents were effective for preventing PPH ≥ 500 mL when compared with placebo or no treatment. The three highest ranked uterotonic agents for prevention of PPH ≥ 500 mL were ergometrine plus oxytocin combination, misoprostol plus oxytocin combination and carbetocin. There is evidence that ergometrine plus oxytocin (RR 0.70, 95% CI 0.59 to 0.84, moderate certainty), carbetocin (RR 0.72, 95% CI 0.56 to 0.93, moderate certainty) and misoprostol plus oxytocin (RR 0.70, 95% CI 0.58 to 0.86, low certainty) may reduce PPH ≥ 500 mL compared with oxytocin. Low-certainty evidence suggests that misoprostol, injectable prostaglandins, and ergometrine may make little or no difference to this outcome compared with oxytocin. All agents except ergometrine and injectable prostaglandins were effective for preventing PPH ≥ 1000 mL when compared with placebo or no treatment. High-certainty evidence suggests that ergometrine plus oxytocin (RR 0.83, 95% CI 0.66 to 1.03) and misoprostol plus oxytocin (RR 0.88, 95% CI 0.70 to 1.11) make little or no difference in the outcome of PPH ≥ 1000 mL compared with oxytocin. Low-certainty evidence suggests that ergometrine may make little or no difference to this outcome compared with oxytocin meanwhile the evidence on carbetocin was of very low certainty. High-certainty evidence suggests that misoprostol is less effective in preventing PPH ≥ 1000 mL when compared with oxytocin (RR 1.19, 95% CI 1.01 to 1.42). Despite the comparable relative treatment effects between all uterotonics (except misoprostol) and oxytocin, ergometrine plus oxytocin, misoprostol plus oxytocin combinations and carbetocin were the highest ranked agents for PPH ≥ 1000 mL. Misoprostol plus oxytocin reduces the use of additional uterotonics (RR 0.56, 95% CI 0.42 to 0.73, high certainty) and probably also reduces the risk of blood transfusion (RR 0.51, 95% CI 0.37 to 0.70, moderate certainty) when compared with oxytocin. Carbetocin, injectable prostaglandins and ergometrine plus oxytocin may also reduce the use of additional uterotonics but the certainty of the evidence is low. No meaningful differences could be detected between all agents for maternal deaths or severe morbidity as these outcomes were rare in the included randomised trials where they were reported. The two combination regimens were associated with important side effects. When compared with oxytocin, misoprostol plus oxytocin combination increases the likelihood of vomiting (RR 2.11, 95% CI 1.39 to 3.18, high certainty) and fever (RR 3.14, 95% CI 2.20 to 4.49, moderate certainty). Ergometrine plus oxytocin increases the likelihood of vomiting (RR 2.93, 95% CI 2.08 to 4.13, moderate certainty) and may make little or no difference to the risk of hypertension, however absolute effects varied considerably and the certainty of the evidence was low for this outcome. Subgroup analyses did not reveal important subgroup differences by mode of birth (caesarean versus vaginal birth), setting (hospital versus community), risk of PPH (high versus low risk for PPH), dose of misoprostol (≥ 600 mcg versus < 600 mcg) and regimen of oxytocin (bolus versus bolus plus infusion versus infusion only). All agents were generally effective for preventing PPH when compared with placebo or no treatment. Ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination may have some additional desirable effects compared with the current standard oxytocin. The two combination regimens, however, are associated with significant side effects. Carbetocin may be more effective than oxytocin for some outcomes without an increase in side effects.

We found 196 studies involving 135,559 women. We compared seven uterotonic agents against each other and against women receiving no uterotonic. Studies were conducted across 53 countries. In most studies women were giving birth normally and in a hospital. The analysis suggests that all drugs are effective for preventing blood loss that equals or exceeds 500 mL when compared with no routine uterotonic treatment. Compared with oxytocin (the standard recommended drug), the three best drugs for this outcome were a combination of ergometrine plus oxytocin, carbetocin, and a combination of misoprostol plus oxytocin. We found the other drugs misoprostol, injectable prostaglandins, and ergometrine may make little or no difference to this outcome compared with oxytocin. All drugs except ergometrine and injectable prostaglandins are effective for preventing blood loss that equals or exceeds 1000 mL when compared with no treatment. Ergometrine plus oxytocin and misoprostol plus oxytocin make little or no difference in this outcome compared with oxytocin. It is uncertain whether carbetocin and ergometrine alone make any difference to this outcome. However, misoprostol is less effective in preventing blood loss that equals or exceeds 1000 mL compared with oxytocin. Misoprostol plus oxytocin reduces the use of additional uterotonics and probably also reduces the risk of blood transfusion when compared with oxytocin. Carbetocin, injectable prostaglandins and ergometrine plus oxytocin may also reduce the use of additional uterotonics but the certainty of the evidence is low. No meaningful differences could be detected between all agents for maternal deaths or severe birth complication as these are rare in such studies. The two combinations of drugs were associated with important side effects. When compared with oxytocin, women receiving misoprostol plus oxytocin combination are more likely to suffer vomiting and fever. Women receiving ergometrine plus oxytocin are also more likely to suffer vomiting and may make little or no difference to the risk of hypertension, however the certainty of the evidence was low for this outcome. The analyses gave similar results irrespective of whether women were giving birth normally or by caesarean, in a hospital or in the community, were at high or low risk for bleeding excessively after birth, whether they received a high or a low dose of misoprostol and whether they received a bolus or an infusion of oxytocin or both. All agents were generally effective for preventing excessive bleeding when compared with no uterotonic drug treatment. Ergometrine plus oxytocin combination, carbetocin, and misoprostol plus oxytocin combination may have some additional benefits compared with the current standard oxytocin. The two combination drugs, however, are associated with significant side effects that women might find disturbing compared with oxytocin. Carbetocin may have some additional benefits compared with oxytocin and appears to be without an increase in side effects.

10.1002/14651858.CD011689.pub3

cochrane-simplification-train-2273

cochrane-simplification-train-2273

We included 31 trials (1760 participants; 897 randomized to peripheral nerve blocks and 863 to no regional blockade). Results of eight trials with 373 participants show that peripheral nerve blocks reduced pain on movement within 30 minutes of block placement (standardized mean difference (SMD) -1.41, 95% confidence interval (CI) -2.14 to -0.67; equivalent to -3.4 on a scale from 0 to 10; I2 = 90%; high quality of evidence). Effect size was proportionate to the concentration of local anaesthetic used (P < 0.00001). Based on seven trials with 676 participants, we did not find a difference in the risk of acute confusional state (risk ratio (RR) 0.69, 95% CI 0.38 to 1.27; I2 = 48%; very low quality of evidence). Three trials with 131 participants reported decreased risk for pneumonia (RR 0.41, 95% CI 0.19 to 0.89; I2 = 3%; number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 5 to 72; moderate quality of evidence). We did not find a difference in risk of myocardial ischaemia or death within six months, but the number of participants included was well below the optimal information size for these two outcomes. Two trials with 155 participants reported that peripheral nerve blocks also reduced time to first mobilization after surgery (mean difference -11.25 hours, 95% CI -14.34 to -8.15 hours; I2 = 52%; moderate quality of evidence). One trial with 75 participants indicated that the cost of analgesic drugs was lower when they were given as a single shot block (SMD -3.48, 95% CI -4.23 to -2.74; moderate quality of evidence). High-quality evidence shows that regional blockade reduces pain on movement within 30 minutes after block placement. Moderate-quality evidence shows reduced risk for pneumonia, decreased time to first mobilization and cost reduction of the analgesic regimen (single shot blocks).

We included 31 trials (1760 adult participants: 897 randomized to peripheral nerve blocks and 863 to no regional blockade) performed in various countries and published between 1980 and 2016. Trials were funded by a charitable organization (n = 3), by a governmental organization (n = 1) or by departmental resources (n = 5), or did not specify the source of funding. Compared with other modes of analgesia, peripheral nerve blocks used to treat hip fracture pain reduce pain on movement better within 30 minutes (equivalent to a difference of -3.4 on a scale from 0 to 10 between the two analgesic regimens). The risk of pneumonia is also reduced when peripheral nerve blocks are used to treat hip fracture pain. For every 7 people with a hip fracture, one less person will suffer from pneumonia. Studies noted no major complications related to peripheral nerve blocks and reported reduced time to first mobilization after hip fracture surgery (approximately 11 hours earlier). We did not identify enough trial participants to determine if regional blockade makes a difference in terms of acute confusion, myocardial ischaemia and death within six months after surgery. Peripheral nerve block given as a single injection led to reduced cost of analgesic drugs. We rated the quality of evidence as high for reduction of pain on movement within 30 minutes, and as moderate for pneumonia, time to first mobilization and costs of analgesic drugs. We would need more information before we could draw final conclusions on effects of peripheral nerve blocks on the risk of acute confusional state, myocardial ischaemia and mortality.

10.1002/14651858.CD001159.pub2

cochrane-simplification-train-2274

cochrane-simplification-train-2274

Two studies were identified (46 participants). One study assessed the efficacy and safety of 12 weeks of LDN (4.5 mg/day) treatment compared to placebo in adult patients (N = 34). The other study assessed eight weeks of LDN (0.1 mg/kg, maximum 4.5 mg/day) treatment compared to placebo in pediatric patients (N = 12). The primary purpose of the pediatric study was to assess safety and tolerability. Both studies were rated as having a low risk of bias. The study in adult patients reported that 30% (5/18) of LDN treated patients achieved clinical remission at 12 weeks compared to 18% (3/16) of placebo patients, a difference that was not statistically significant (RR 1.48, 95% CI 0.42 to 5.24). The study in children reported that 25% of LDN treated patients achieved clinical remission (PCDAI < 10) compared to none of the patients in the placebo group, although it was unclear if this result was for the randomized placebo-controlled trial or for the open label extension study. In the adult study 70-point clinical response rates were significantly higher in those treated with LDN than placebo. Eighty-three per cent (15/18) of LDN patients had a 70-point clinical response at week 12 compared to 38% (6/16) of placebo patients (RR 2.22, 95% CI 1.14 to 4.32). The effect of LDN on the proportion of adult patients who achieved a 100-point clinical response was uncertain. Sixty-one per cent (11/18) of LDN patients achieved a 100-point clinical response compared to 31% (5/16) of placebo patients (RR 1.96, 95% CI 0.87 to 4.42). The proportion of patients who achieved endoscopic response (CDEIS decline > 5 from baseline) was significantly higher in the LDN group compared to placebo. Seventy-two per cent (13/18) of LDN patients achieved an endoscopic response compared to 25% (4/16) of placebo patients (RR 2.89; 95% CI 1.18 to 7.08). However, there was no statistically significant difference in the proportion of patients who achieved endoscopic remission. Endoscopic remission (CDEIS < 3) was achieved in 22% (4/18) of the LDN group compared to 0% (0/16) of the placebo group (RR 8.05; 95% CI 0.47 to 138.87). Pooled data from both studies show no statistically significant differences in withdrawals due to adverse events or specific adverse events including sleep disturbance, unusual dreams, headache, decreased appetite, nausea and fatigue. No serious adverse events were reported in either study. GRADE analyses rated the overall quality of the evidence for the primary and secondary outcomes (i.e. clinical remission, clinical response, endoscopic response, and adverse events) as low due to serious imprecision (sparse data). Currently, there is insufficient evidence to allow any firm conclusions regarding the efficacy and safety of LDN used to treat patients with active Crohn's disease. Data from one small study suggests that LDN may provide a benefit in terms of clinical and endoscopic response in adult patients with active Crohn’s disease. Data from two small studies suggest that LDN does not increase the rate of specific adverse events relative to placebo. However, these results need to be interpreted with caution as they are based on very small numbers of patients and the overall quality of the evidence was rated as low due to serious imprecision. Further randomized controlled trials are required to assess the efficacy and safety of LDN therapy in active Crohn's disease in both adults and children.

This review identified two small randomized controlled trials that included a total of 46 participants. One study compared 12 weeks of treatment with low dose naltrexone (4.5 mg/day) to a placebo (i.e. a fake drug such as a sugar pill) in 34 adult patients with active Crohn’s disease. The other study compared eight weeks of treatment with low dose naltrexone (0.1 mg/kg up to a maximum 4.5 mg/day) to a placebo in 12 children with active Crohn's disease. The results from both studies were imprecise with regard to the proportion of patients who achieved clinical remission. The results of the study in adult patients suggest that low dose naltrexone may provide a benefit in terms of clinical response (i.e. an improvement in disease symptoms) and endoscopic response (i.e. a reduction in inflammation of the gut as shown by examining the gut with a scope). We could not tell whether low dose naltrexone led to specific side effects including sleep disturbance, unusual dreams, headache, decreased appetite, nausea and fatigue due to the low number of people who experienced these problems in the studies. The results of this review need to be interpreted with caution as they are based on small numbers of patients and the overall quality of the evidence was rated as low due to lack of precision of the results. Thus no firm conclusions can be made regarding the effectiveness and side effect profile of low dose naltrexone treatment for patients with active Crohn's disease. Further randomized controlled trials are required to assess the effectiveness and side effects of low dose naltrexone therapy in active Crohn's disease in both adults and children.

10.1002/14651858.CD010410.pub3

cochrane-simplification-train-2275

cochrane-simplification-train-2275

We included three trials (283 participants in the analyses) that ran for two to three years. All participants were ex- or never-smokers and had genetic variants that carried a high risk of developing COPD. Only one trial reported mortality data (one person of 93 died in the treatment group and three of 87 died in the placebo group). There was no information on harms in the oldest trial. Another trial reported serious adverse events in 10 participants in the treatment group and 18 participants in the placebo group. In the most recent trial, serious adverse events occurred in 28 participants in each group. None of the trials reported mean number of lung infections or hospital admissions. In the two trials that reported exacerbations, there were more exacerbations in the treatment group than in the placebo group, but the results of both trials included the possibility of no difference. Quality of life was similar in the two groups. Forced expiratory volume in one second (FEV1) deteriorated more in participants in the treatment group than in the placebo group but the confidence interval (CI) included no difference (standardised mean difference -0.19, 95% CI -0.42 to 0.05; P = 0.12). For carbon monoxide diffusion, the difference was -0.11 mmol/minute/kPa (95% CI -0.35 to 0.12; P = 0.34). Lung density measured by computer tomography (CT) scan deteriorated significantly less in the treatment group than in the placebo group (mean difference (MD) 0.86 g/L, 95% CI 0.31 to 1.42; P = 0.002). Several secondary outcomes were unreported in the largest and most recent trial whose authors had numerous financial conflicts of interest. This review update added one new study and 143 new participants, but the conclusions remain unchanged. Due to sparse data, we could not arrive at a conclusion about the impact of augmentation therapy on mortality, exacerbations, lung infections, hospital admission and quality of life, and there was uncertainty about possible harms. Therefore, it is our opinion that augmentation therapy with alpha-1 antitrypsin cannot be recommended.

We reviewed the benefits and harms of treating patients who have the form of the disease that affects the lungs with alpha-1 antitrypsin extracted from blood donations. We found three randomised clinical trials (283 participants in the analyses) comparing treatment with alpha-1 antitrypsin with placebo (a pretend treatment) for two to three years. All participants were ex-smokers or had never smoked but had the genetic problem that carried a high risk of developing lung problems. The evidence is current to March 2016. Only one trial reported deaths (one of 93 participants died taking the medicine and three of 87 died taking placebo). There was no information on harms in the oldest trial. In another trial, serious adverse events occurred in 10 participants in the medicine group and 18 participants in the placebo group. In the most recent trial, serious adverse events occurred in 28 participants in each group. None of the trials reported on the number of lung infections or hospital admissions. There were more exacerbations (acute worsening in lung function) in the medicine group than in the placebo group, whereas quality of life was similar in the two groups. All trials measured lung function using forced expiratory volume in one second (how much air a person can breathe out during a forced breath) and carbon monoxide diffusion (a medical test that measures how much gas travels from the lungs to the blood). Lung function was slightly worse in participants taking the medicine but the differences were not significant. Lung function deteriorated significantly less when measured by a special type of X-ray called a computer tomography (CT) scan. Several secondary outcomes were unreported in the largest and most recent trial whose authors had numerous financial conflicts of interest. Due to a lack of information, we cannot be sure whether this treatment works or not. Therefore, it is our opinion that treatment with alpha-1 antitrypsin augmentation cannot be recommended.

10.1002/14651858.CD007851.pub3

cochrane-simplification-train-2276

cochrane-simplification-train-2276

The search identified two studies (a multicenter study from Japan and the United Kingdom) with 361 participants. Primary outcomes Our results indicate that single-dose intravesical chemotherapy instillation may reduce the risk of bladder cancer recurrence over time compared to no instillation (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.32 to 0.82, low-certainty evidence). After 12 months follow-up, this would result in 127 fewer bladder cancer recurrences (95% CI: 182 to 44 fewer bladder cancer recurrences) per 1000 participants. We downgraded the certainty of evidence by two levels due to study limitations and imprecision. We found no trials that reported on the outcomes of time to death from upper tract urothelial carcinoma. The effect of single-dose intravesical chemotherapy instillation on serious adverse events is uncertain (risk ratio [RR]: not estimable, 95% CI: not estimable, there were no events, very low-certainty evidence). We downgraded the certainty of evidence by one level due to study limitations and by two levels due to imprecision. Secondary outcomes We found no trials that reported on the outcomes of time to death from any cause and participants’ disease-specific quality of life. The effect of single-dose intravesical chemotherapy instillation on minor adverse events is uncertain (risk ratio [RR]: not estimable, 95% CI: not estimable, there were no events, very low-certainty evidence). We downgraded the certainty of evidence by one level due to study limitations and by two levels due to imprecision. For patients who have undergone nephroureterectomy for upper tract urothelial carcinoma, single-dose intravesical chemotherapy instillation may reduce bladder cancer recurrence after nephroureterectomy. However, we are uncertain as to the risk of serious (and minor) adverse events. We found no evidence for the outcome of time to death from upper tract urothelial carcinoma. We were unable to conduct any of the preplanned subgroup analyses, particularly those based on operative approach, pathologic stage, and method of bladder cuff excision.

We found two randomised controlled studies (RCTs), with a total of 361 participants that compared a single-dose chemotherapy placed in the bladder to no chemotherapy in people having their kidney and ureter removed for cancer of the inner lining of the kidney or ureter, or both. These findings are based on a literature search up to April 15, 2019. We found that a one-time dose of chemotherapy put into the bladder after surgery may reduce the risk of this type of tumor coming back in the bladder over time compared to no chemotherapy. We found no evidence whether this affects the time to death from this type of cancer. Serious unwanted effects appear to be rare and not increased with chemotherapy, but we are uncertain of this finding. Our confidence in the evidence for the effect on the risk of recurrence within the bladder is low. This means that the true effect may be very different from what this review shows. The certainty of evidence for the effects of one-time chemotherapy put into the bladder on serious unwanted effects was very low. This means that we are very uncertain about this result.

10.1002/14651858.CD013160.pub2

cochrane-simplification-train-2277

cochrane-simplification-train-2277

We identified 16 trials, predominantly of moderate to good quality, involving 994 participants, most with chronic obstructive pulmonary disease (COPD). Compared with IPPV weaning, NPPV weaning significantly decreased mortality. The benefits for mortality were significantly greater in trials enrolling exclusively participants with COPD (risk ratio (RR) 0.36, 95% confidence interval (CI) 0.24 to 0.56) versus mixed populations (RR 0.81, 95% CI 0.47 to 1.40). NPPV significantly reduced weaning failure (RR 0.63, 95% CI 0.42 to 0.96) and ventilator-associated pneumonia (RR 0.25, 95% CI 0.15 to 0.43); shortened length of stay in an intensive care unit (mean difference (MD) -5.59 days, 95% CI -7.90 to -3.28) and in hospital (MD -6.04 days, 95% CI -9.22 to -2.87); and decreased the total duration of ventilation (MD -5.64 days, 95% CI -9.50 to -1.77) and the duration of endotracheal mechanical ventilation (MD - 7.44 days, 95% CI -10.34 to -4.55) amidst significant heterogeneity. Noninvasive weaning also significantly reduced tracheostomy (RR 0.19, 95% CI 0.08 to 0.47) and reintubation (RR 0.65, 95% CI 0.44 to 0.97) rates. Noninvasive weaning had no effect on the duration of ventilation related to weaning. Exclusion of a single quasi-randomized trial did not alter these results. Subgroup analyses suggest that the benefits for mortality were significantly greater in trials enrolling exclusively participants with COPD versus mixed populations. Summary estimates from 16 trials of moderate to good quality that included predominantly participants with COPD suggest that a weaning strategy that includes NPPV may reduce rates of mortality and ventilator-associated pneumonia without increasing the risk of weaning failure or reintubation.

Results from 16 randomized controlled trials, predominantly of moderate to good quality, involving 994 selected participants, approximately two thirds with chronic obstructive pulmonary disease who had respiratory failure and were starting to breathe spontaneously, demonstrate that support with noninvasive ventilation can decrease death, weaning failure, pneumonia and length of stay in the intensive care unit and hospital. Noninvasive weaning also decreased the total duration of ventilation and the time spent on invasive ventilation, as well as the number of participants who received a tracheostomy. Although noninvasive weaning had no effect on the duration of mechanical ventilation related to weaning, it did not increase the reintubation rate. Insufficient data were available to assess its impact on quality of life. Noninvasive weaning significantly reduced mortality in chronic obstructive pulmonary disease studies versus mixed population studies.

10.1002/14651858.CD004127.pub3

cochrane-simplification-train-2278

cochrane-simplification-train-2278

48 studies (n = 3054 participants) were included. The review supported the efficacy of CBT and particularly CBT-BN in the treatment of people with bulimia nervosa and also (but less strongly due to the small number of trials) related eating disorder syndromes. Other psychotherapies were also efficacious, particularly interpersonal psychotherapy in the longer-term. Self-help approaches that used highly structured CBT treatment manuals were promising. Exposure and Response Prevention did not enhance the efficacy of CBT. Psychotherapy alone is unlikely to reduce or change body weight in people with bulimia nervosa or similar eating disorders. There is a small body of evidence for the efficacy of CBT in bulimia nervosa and similar syndromes, but the quality of trials is very variable and sample sizes are often small. More and larger trials are needed, particularly for binge eating disorder and other EDNOS syndromes. There is a need to develop more efficacious therapies for those with both a weight and an eating disorder.

We reviewed studies of psychotherapies, including a specific form of psychotherapy called cognitive behavioural therapy (CBT-BN). We compared psychotherapy to control groups who got no treatment (e.g. people on waiting lists) and the specific CBT-BN with other types of psychotherapy. We found that CBT was better than other therapies, and better than no treatment, at reducing binge eating. Other psychotherapies were also better than no treatment in reducing binge eating. Some studies found that self-help using the CBT manual can be helpful, but more research and larger trials are needed.

10.1002/14651858.CD000562.pub3

cochrane-simplification-train-2279

cochrane-simplification-train-2279

We included 12 studies (n = 1837), of which, three compared PCT to a wait-list/minimal attention (WL/MA) group and 11 compared PCT to TF-CBT. PCT was more effective than WL/MA in reducing PTSD symptom severity (SMD -0.84, 95% CI -1.10 to -0.59; participants = 290; studies = 3; I² = 0%). We assessed the quality of this evidence as moderate. The results of the non-inferiority analysis comparing PCT to TF-CBT did not support PCT non-inferiority, with the 95% confidence interval surpassing the clinically meaningful cut-off (MD 6.83, 95% CI 1.90 to 11.76; 6 studies, n = 607; I² = 42%). We assessed this quality of evidence as low. CAPS differences between PCT and TF-CBT attenuated at 6-month (MD 1.59, 95% CI -0.46 to 3.63; participants = 906; studies = 6; I² = 0%) and 12-month (MD 1.22, 95% CI -2.17 to 4.61; participants = 485; studies = 3; I² = 0%) follow-up periods. To confirm the direction of the treatment effect using all eligible trials, we also evaluated PTSD SMD differences. These results were consistent with the primary MD outcomes, with meaningful effect size differences between PCT and TF-CBT at post-treatment (SMD 0.32, 95% CI 0.08 to 0.56; participants = 1129; studies = 9), but smaller effect size differences at six months (SMD 0.17, 95% CI 0.05 to 0.29; participants = 1339; studies = 9) and 12 months (SMD 0.17, 95% CI 0.03 to 0.31; participants = 728; studies = 5). PCT had approximately 14% lower treatment dropout rates compared to TF-CBT (RD -0.14, 95% CI -0.18 to -0.10; participants = 1542; studies = 10). We assessed the quality of this evidence as moderate. There was no evidence of meaningful differences on self-reported PTSD (MD 4.50, 95% CI 3.09 to 5.90; participants = 983; studies = 7) or depression symptoms (MD 1.78, 95% CI -0.23 to 3.78; participants = 705; studies = 5) post-treatment. Moderate-quality evidence indicates that PCT is more effective in reducing PTSD severity compared to control conditions. Low quality of evidence did not support PCT as a non-inferior treatment compared to TF-CBT on clinician-rated post-treatment PTSD severity. The treatment effect differences between PCT and TF-CBT may attenuate over time. PCT participants drop out of treatment at lower rates relative to TF-CBT participants. Of note, all of the included studies were primarily designed to test the effectiveness of TF-CBT which may bias results away from PCT non-inferiority.The current systematic review provides the most rigorous evaluation to date to determine whether PCT is comparably as effective as TF-CBT. Findings are generally consistent with current clinical practice guidelines that suggest that PCT may be offered as a treatment for PTSD when TF-CBT is not available.

This review included 12 studies that comprised a total of 1837 participants. Eleven studies that included 1826 participants contributed to the quantitative syntheses. Participants were all adults, but ranged in demographics and trauma types. All studies recruited participants in the United States and there was a predominance of studies conducted on military veterans. PCT does not appear to be as effective as trauma focused treatments in reducing PTSD severity at post-treatment. However, PCT is associated with reduced treatment dropout rates compared to TF-CBT. Several of the TF-CBT trials included in this review were well designed and executed. However, we assessed the overall quality of evidence for our primary outcome (post-treatment PTSD severity) as low based on inconsistent outcomes and some imprecision in the results. We rated the quality of the evidence on differential treatment dropout as moderate.

10.1002/14651858.CD012898.pub2

cochrane-simplification-train-2280

cochrane-simplification-train-2280

We found 1952 potential titles, with a most recent search date of February 2019, of which five RCTs of varying quality and size met the inclusion criteria. These studies assessed a total of 1713 women with stage IIIc/IV ovarian cancer randomised to NACT followed by interval debulking surgery (IDS) or PDS followed by chemotherapy. We pooled results of the three studies where data were available and found little or no difference with regard to overall survival (OS) (1521 women; hazard ratio (HR) 1.06; 95% confidence interval (CI) 0.94 to 1.19, I2 = 0%; moderate-certainty evidence) or progression-free survival in four trials where we were able to pool data (1631 women; HR 1.02; 95% CI 0.92 to 1.13, I2 = 0%; moderate-certainty evidence). Adverse events, surgical morbidity and quality of life (QoL) outcomes were poorly and incompletely reported across studies. There may be clinically meaningful differences in favour of NACT compared to PDS with regard to serious adverse effects (SAE grade 3+). These data suggest that NACT may reduce the risk of need for blood transfusion (risk ratio (RR) 0.80; 95% CI 0.64 to 0.99; four studies,1085 women; low-certainty evidence), venous thromboembolism (RR 0.28; 95% CI 0.09 to 0.90; four studies, 1490 women; low-certainty evidence), infection (RR 0.30; 95% CI 0.16 to 0.56; four studies, 1490 women; moderate-certainty evidence), compared to PDS. NACT probably reduces the need for stoma formation (RR 0.43, 95% CI 0.26 to 0.72; two studies, 581 women; moderate-certainty evidence) and bowel resection (RR 0.49, 95% CI 0.26 to 0.92; three studies, 1213 women; moderate-certainty evidence), as well as reducing postoperative mortality (RR 0.18; 95% CI 0.06 to 0.54:five studies, 1571 women; moderate-certainty evidence). QoL on the EORTC QLQ-C30 scale produced inconsistent and imprecise results in two studies (MD -1.34, 95% CI -2.36 to -0.32; participants = 307; very low-certainty evidence) and use of the QLQC-30 and QLQC-Ov28 in another study (MD 7.60, 95% CI 1.89 to 13.31; participants = 217; very low-certainty evidence) meant that little could be inferred. The available moderate-certainty evidence suggests there is little or no difference in primary survival outcomes between PDS and NACT. NACT may reduce the risk of serious adverse events, especially those around the time of surgery, and the need for bowel resection and stoma formation. These data will inform women and clinicians and allow treatment to be tailored to the person, taking into account surgical resectability, age, histology, stage and performance status. Data from an unpublished study and ongoing studies are awaited.

We found 1952 potential titles. From these we found five studies which met our inclusion criteria, including a total of 1713 women with advanced ovarian cancer. We were able to pool data from four studies. These studies compared women who were given chemotherapy prior to surgery (NACT) with women who underwent surgery first (PDS) prior to chemotherapy. We found little or no difference between the two treatments with respect to the time to death or the time to progression of the disease. We found that giving NACT probably reduces the risk of some complications of surgery, but these data were less well reported in the included studies and so we have low certainty about these results. The studies only enrolled women with stage IIIc/IV ovarian cancer i.e. those who had advanced disease; a large proportion of women in this review had very bulky tumours. We are currently awaiting results of two ongoing studies and one unpublished study that will hopefully contribute more evidence to guide clinical practice in this area in the future. Overall, the evidence was of moderate certainty. There is probably little or no difference in how long women with advanced epithelial ovarian cancer will survive, if they have chemotherapy or surgery first, where both treatments are planned. NACT may reduce some of the risks of surgery, and probably halves the risk of needing bowel removed and/or the bowel diverted through the abdominal wall via a stoma (a bag attached to the abdominal wall to collect bowel contents). NACT/IDS is an alternative to PDS followed by chemotherapy in women with bulky stage IIIc/IV disease. Individual decisions about which treatment to have first will depend on the individual woman's wishes, how well she is at the time of diagnosis, the risks of surgery and the burden and distribution of disease.

10.1002/14651858.CD005343.pub4

cochrane-simplification-train-2281

cochrane-simplification-train-2281

Five studies met our inclusion criteria; all were retrospective observational studies and therefore at high risk of bias. Meta-analysis of three studies assessing over 9000 women suggested that institutions with gynaecologic oncologists on site may prolong survival in women with ovarian cancer, compared to community or general hospitals: hazard ratio (HR) of death was 0.90 (95% confidence interval (CI) 0.82 to 0.99). Similarly, another meta-analysis of three studies assessing over 50,000 women, found that teaching centres or regional cancer centres may prolong survival in women with any gynaecological cancer compared to community or general hospitals (HR 0.91; 95% CI 0.84 to 0.99). The largest of these studies included all gynaecological malignancies and assessed 48,981 women, so the findings extend beyond ovarian cancer. One study compared community hospitals with semi-specialised gynaecologists versus general hospitals and reported non-significantly better disease-specific survival in women with ovarian cancer (HR 0.89; 95% CI 0.78 to 1.01). The findings of included studies were highly consistent. Adverse event data were not reported in any of the studies. We found low quality, but consistent evidence to suggest that women with gynaecological cancer who received treatment in specialised centres had longer survival than those managed elsewhere. The evidence was stronger for ovarian cancer than for other gynaecological cancers. Further studies of survival are needed, with more robust designs than retrospective observational studies. Research should also assess the quality of life associated with centralisation of gynaecological cancer care. Most of the available evidence addresses ovarian cancer in developed countries; future studies should be extended to other gynaecological cancers within different healthcare systems.

We used a set of tests to ensure that the evidence the five studies identified reached the quality standard for our analysis.The analysis of three studies combined (meta-analysis), assessing over 9000 women, suggested that institutions with gynaecologic oncologists (specialists in the field of gynaecological cancer treatment) on site may prolong the lives of women with ovarian cancer compared to community or general hospitals. Similarly, another meta-analysis of three studies which assessed well over 50,000 women, found evidence to suggest that teaching centres or regional cancer centres (specialised centres) may prolong the lives of women with gynaecological cancer compared to community or general hospitals. The largest study in this meta-analysis assessed all gynaecological cancers in 48,981 women, so it had major influence on the final result; this means that our findings are likely to be relevant to other gynaecological cancers, besides ovarian cancer. Overall, the findings suggest that centralisation of care may prolong the lives of women with gynaecological cancer, and in particular ovarian cancer. However, the results should be interpreted with caution as all of the studies included in the review could be biased. For example, it is possible that the patients who were treated in specialised centres were less ill to begin with. Another weakness of the review is that only one of the studies included women with gynaecological cancers other than ovarian cancer. Ideally, further studies in this area are needed.  New studies should be designed to avoid the possibility of bias due to the treatment of women at specialist and non-specialist centres being systematically different. Additionally, studies should assess the impact of centralisation of care on the quality of life of patients. Most of the available evidence was about ovarian cancer in developed countries; future studies should be extended to other gynaecological cancers and to less developed countries.

10.1002/14651858.CD007945.pub2

cochrane-simplification-train-2282

cochrane-simplification-train-2282

All 36 included trials originated from China and were at overall high risk of bias. The trials included 6044 pregnant women who were HBsAg, HBeAg, or hepatitis B virus DNA (HBV-DNA) positive. Only seven trials reported inclusion of HBeAg-positive mothers. All 36 trials compared HBIG versus no intervention. None of the trials used placebo. Most of the trials assessed HBIG 100 IU (two trials) and HBIG 200 IU (31 trials). The timing of administration of HBIG varied; 30 trials administered three doses of HBIG 200 IU at 28, 32, and 36 weeks of pregnancy. None of the trials reported all-cause mortality or other serious adverse events in the mothers or babies. Serological signs of hepatitis B infection of the newborns were reported as HBsAg, HBeAg, and HBV-DNA positive results at end of follow-up. Twenty-nine trials reported HBsAg status in newborns (median 1.2 months of follow-up after birth; range 0 to 12 months); seven trials reported HBeAg status (median 1.1 months of follow-up after birth; range 0 to 12 months); and 16 trials reported HBV-DNA status (median 1.2 months of follow-up; range 0 to 12 months). HBIG reduced mother-to-child transmission (MTCT) of HBsAg when compared with no intervention (179/2769 (6%) with HBIG versus 537/2541 (21%) with no intervention; RR 0.30, TSA-adjusted CI 0.20 to 0.52; I2 = 36%; 29 trials; 5310 participants; very low quality evidence). HBV-DNA reduced MTCT of HBsAg (104/1112 (9%) with HBV-DNA versus 382/1018 (38%) with no intervention; RR 0.25, TSA-adjusted CI 0.22 to 0.27; I2 = 84%; 16 trials; 2130 participants; low quality evidence). TSA supported both results. Meta-analysis showed that maternal HBIG did not decrease HBeAg in newborns compared with no intervention (184/889 (21%) with HBIG versus 232/875 (27%) with no intervention; RR 0.68, TSA-adjusted CI 0.04 to 6.37; I2 = 90%; 7 trials; 1764 participants; very low quality evidence). TSA could neither support nor refute this observation as data were too sparse. None of the trials reported adverse events of the immunoglobulins on the newborns, presence of local and systemic adverse events on the mothers, or cost-effectiveness of treatment. Due to very low to low quality evidence found in this review, we are uncertain of the effect of benefit of antenatal HBIG administration to the HBV-infected mothers on newborn outcomes, such as HBsAg, HBV-DNA, and HBeAg compared with no intervention. The results of the effects of HBIG on HBsAg and HBeAg are surrogate outcomes (raising risk of indirectness), and we need to be critical while interpreting the findings. We found no data on newborn mortality or maternal mortality or both, or other serious adverse events. Well-designed randomised clinical trials are needed to determine the benefits and harms of HBIG versus placebo in prevention of MTCT of HBV.

After searching the medical literature for relevant trials, we identified 36 clinical trials that recruited 6044 pregnant women with signs of HBV infection. All trials originated from China. All trials and trial results were at high risks of bias, which makes potential overestimation of benefits and underestimation of harms more likely. The studies assessed only hepatitis B surface antigen (HBsAg) (proteins on the surface of the HBV that cause immune system of the body to make antibodies when exposed to HBV), hepatitis B virus DNA (HBV-DNA) (self-dividing material of the HBV which carries its genetic information), and hepatitis B envelope antigen (HBeAg) (blood proteins that shows that the virus is still active in the liver) status in newborns. There was no information about the effects of HBIG on death from all causes (newborn or mother), antibodies to hepatitis B core antigen (proteins made by the immune system which bind to HBV and cause them to be destroyed), cost-effectiveness of HBIG, and side effects. Antenatal (before birth) HBIG might have an effect on preventing mother-to-child transmission of HBV as more treated babies than non-treated babies had no HBsAg or HBV-DNA; however, both results could have been affected by the way the trials were conducted and were at high risk of bias. The authors could draw no conclusions about the side effects of HBIG for pregnant women with HBV infection. Well-designed clinical trials with low risks of bias are needed to establish the benefits and harms of HBIG compared with no treatment in pregnant women with HBV. Due to the very low to low quality evidence in this review, we do not know if antenatal HBIG administration has an effect on the proportion of newborns with HBsAg and HBV-DNA compared with no treatment. We could draw no conclusions about death of newborns or mothers as we found no data.

10.1002/14651858.CD008545.pub2

cochrane-simplification-train-2283

cochrane-simplification-train-2283

We included 33 trials, involving 13,114 children (˜49% females) from 20 countries in Latin America, Africa and Asia. The methodological quality of the trials was mixed. Nineteen trials evaluated intermittent iron supplementation versus no intervention or a placebo and 21 studies evaluated intermittent versus daily iron supplementation. Some of these trials contributed data to both comparisons. Iron alone was provided in most of the trials. Fifteen studies included children younger than 60 months; 11 trials included children 60 months and older, and seven studies included children in both age categories. One trial included exclusively females. Seven trials included only anaemic children; three studies assessed only non-anaemic children, and in the rest the baseline prevalence of anaemia ranged from 15% to 90%. In comparison with receiving no intervention or a placebo, children receiving iron supplements intermittently have a lower risk of anaemia (average risk ratio (RR) 0.51, 95% confidence interval (CI) 0.37 to 0.72, ten studies) and iron deficiency (RR 0.24, 95% CI 0.06 to 0.91, three studies) and have higher haemoglobin (mean difference (MD) 5.20 g/L, 95% CI 2.51 to 7.88, 19 studies) and ferritin concentrations (MD 14.17 µg/L, 95% CI 3.53 to 24.81, five studies). Intermittent supplementation was as effective as daily supplementation in improving haemoglobin (MD –0.60 g/L, 95% CI –1.54 to 0.35, 19 studies) and ferritin concentrations (MD –4.19 µg/L, 95% CI –9.42 to 1.05, 10 studies), but increased the risk of anaemia in comparison with daily iron supplementation (RR 1.23, 95% CI 1.04 to1.47, six studies). Data on adherence were scarce and it tended to be higher among those children receiving intermittent supplementation, although this result was not statistically significant. We did not identify any differential effect of the type of intermittent supplementation regimen (one, two or three times a week), the total weekly dose of elemental iron, the nutrient composition, whether recipients were male or female or the length of the intervention. Intermittent iron supplementation is efficacious to improve haemoglobin concentrations and reduce the risk of having anaemia or iron deficiency in children younger than 12 years of age when compared with a placebo or no intervention, but it is less effective than daily supplementation to prevent or control anaemia. Intermittent supplementation may be a viable public health intervention in settings where daily supplementation has failed or has not been implemented. Information on mortality, morbidity, developmental outcomes and side effects, however, is still lacking.

The studies were of mixed quality. Overall, the results of this review show that giving children supplements with iron alone or in combination with other vitamins and minerals one, two or three times a week approximately halves their risk of having anaemia in comparison with receiving no iron supplements or a placebo. Giving children supplements on a intermittent basis was as effective as daily supplementation for improving haemoglobin and ferritin concentrations, although, children receiving iron supplements intermittently were at higher risk of having anaemia. We aimed to examine the effects of intermittent supplementation on illness, death, and school and physical performance, as well as on other side effects, but there was insufficient information to draw firm conclusions. In summary, intermittent iron supplementation is efficacious to improve haemoglobin concentrations and reduce the risk of having anaemia or iron deficiency in children younger than 12 years of age when compared with a placebo or no intervention, but it is less effective than daily supplementation to prevent or control anaemia. Intermittent supplementation may be a viable public health intervention in settings where daily supplementation has failed or has not been implemented. Information on mortality, morbidity, developmental outcomes and side effects, however, is still lacking.

10.1002/14651858.CD009085.pub2

cochrane-simplification-train-2284

cochrane-simplification-train-2284

Two randomised controlled trials with a total of 141 preterm infants met the inclusion criteria for the comparison of routine monitoring versus no monitoring of gastric residual in preterm infants. Both trials were done in infants with birth weight < 1500 g. Routine monitoring of gastric residual may have little or no effect on the incidence of necrotising enterocolitis (risk ratio (RR) 3.07, 95% confidence interval (CI) 0.50 to 18.77; participants = 141; studies = 2; low-quality evidence). Routine monitoring may increase the risk of feed interruption episodes (RR 2.07, 95% CI 1.39 to 3.07; participants = 141; studies = 2; low-quality evidence); the number needed to treat for an additional harmful outcome (NNTH) was 3 (95% CI 2 to 6). Routine monitoring of gastric residual may increase time taken to establish full enteral feeds (mean difference (MD) 3.92, 95% CI 2.06 to 5.77 days; participants = 141; studies = 2; low-quality evidence), time taken to regain birth weight (MD 1.70, 95% CI 0.01 to 3.39 days; participants = 80; studies = 1; low-quality evidence), and number of total parenteral nutrition days (MD 3.29, 95% CI 1.66 to 4.92 days; participants = 141; studies = 2; low-quality evidence). We are uncertain as to the effect of routine monitoring of gastric residual on other outcomes such as incidence of surgical necrotising enterocolitis, extrauterine growth restriction at discharge, parenteral nutrition-associated liver disease, duration of central venous line (CVL) usage, incidence of invasive infection, mortality before discharge, and duration of hospital stay. We found no data for outcomes such as aspiration pneumonia, gastroesophageal reflux, growth measures following discharge, and neurodevelopmental outcome. Only one trial with 87 preterm infants met the inclusion criteria for the comparison of using two different criteria of gastric residual to interrupt feeds while monitoring gastric residual. The trial was done in infants with birth weight of 1500 to 2000 g. We are uncertain as to the effect of using two different criteria of gastric residual on outcomes such as incidence of necrotising enterocolitis or surgical necrotising enterocolitis, time to establish full enteral feeds, time to regain birth weight, number of total parenteral nutrition days, number of infants experiencing feed interruption episodes, extrauterine growth restriction at discharge, parenteral nutrition-associated liver disease, incidence of invasive infection, and mortality before discharge (very low quality evidence). We found no data on duration of CVL usage, aspiration pneumonia, gastroesophageal reflux, duration of hospital stay, growth measures following discharge, and neurodevelopmental outcome. Review authors found insufficient evidence as to whether routine monitoring of gastric residual reduces the incidence of necrotising enterocolitis because trial results are imprecise. Low-quality evidence suggests that routine monitoring of gastric residual increases the risk of feed interruption episodes, increases the time taken to reach full enteral feeds and to regain birth weight, and increases the number of total parenteral nutrition (TPN) days. Available data are insufficient to comment on other major outcomes such as incidence of invasive infection, parenteral nutrition-associated liver disease, mortality before discharge, extrauterine growth restriction at discharge, number of CVL days, and duration of hospital stay. Further randomised controlled trials are warranted to provide more precise estimates of the effects of routine monitoring of gastric residual on important outcomes, especially necrotising enterocolitis, in preterm infants.

The literature searches are up-to-date as of 19 February 2018. We found two small randomised controlled trials with a total of 141 preterm infant participants that compared routine monitoring versus no monitoring of stomach aspirates in preterm infants. We found one trial for the comparison of using two different criteria of aspirates to interrupt feeds while monitoring stomach aspirates in preterm infants. There is uncertainty as to whether routine monitoring of stomach aspirates reduces necrotising enterocolitis because trial results are imprecise. Preterm infants on routine monitoring of stomach aspirates may reach full feeds later, regain birth weight later, require longer duration of parenteral nutrition, and may be at increased risk of feed interruption episodes. There is uncertainty as to whether using two different criteria of gastric residual to interrupt feeds has effect on important outcomes in preterm infants. There is uncertainty as to whether routine monitoring of stomach aspirates has any benefits. Routine monitoring may increase the number of feed interruption episodes and the time taken to reach full feeds.

10.1002/14651858.CD012937.pub2

cochrane-simplification-train-2285

cochrane-simplification-train-2285

There were 15 included studies (6008 enrolled participants); 13 studies contributed data. Women using home uterine monitoring were less likely to experience preterm birth at less than 34 weeks (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.62 to 0.99; three studies, 1596 women; fixed-effect analysis) (GRADE high). This difference was not evident when we carried out a sensitivity analysis, restricting the analysis to studies at low risk of bias based on study quality (RR 0.75, 95% CI 0.57 to 1.00; one study, 1292 women). There was no difference in the rate of perinatal mortality (RR 1.22, 95% CI 0.86 to 1.72; two studies, 2589 babies) (GRADE low). There was no difference in the number of preterm births at less than 37 weeks (average RR 0.85, CI 0.72 to 1.01; eight studies, 4834 women; random-effects, Tau2 = 0.03, I2 = 68%) (GRADE very low). Infants born to women using home uterine monitoring were less likely to be admitted to neonatal intensive care unit (average RR 0.77, 95% CI 0.62 to 0.96; five studies, 2367 babies; random-effects, Tau2 = 0.02, I2 = 32%) (GRADE moderate). This difference was not maintained when we restricted the analysis to studies at low risk of bias (RR 0.86, 95% CI 0.74 to 1.01; one study, 1292 babies). Women using home uterine monitoring made more unscheduled antenatal visits (mean difference (MD) 0.48, 95% CI 0.31 to 0.64; two studies, 1994 women) (GRADE moderate). Women using home uterine monitoring were also more likely to have prophylactic tocolytic drug therapy (average RR 1.21, 95% CI 1.01 to 1.45; seven studies, 4316 women; random-effects, Tau2 = 0.03, I2 = 62%), but this difference was no longer evident when we restricted the analysis to studies at low risk of bias (average RR 1.22, 95% CI 0.90 to 1.65; three studies, 3749 women; random-effects, Tau2 = 0.05, I2 = 76%) (GRADE low). The number of antenatal hospital admissions did not differ between home groups (RR 0.91, 95% CI 0.74 to 1.11; three studies, 1494 women (GRADE low)). We found no data on maternal anxiety or acceptability. Home uterine monitoring may result in fewer admissions to a neonatal intensive care unit but in more unscheduled antenatal visits and tocolytic treatment; the level of evidence is generally low to moderate. Important group differences were not evident when we undertook sensitivity analysis using only trials at low risk of bias. There is no impact on maternal and perinatal outcomes such as perinatal mortality or incidence of preterm birth.

We searched for evidence on 28 June 2016 and found 15 randomised studies, involving 6008 women. Thirteen of these studies provided data we could use. The quality of results ranged from very low to high (GRADE). Most studies had design limitations, which in some were serious. Most studies compared women taught how to check for signs of premature labour with women who were also given a home uterine activity monitor. In some studies both groups used a monitor but one group had a ‘sham’ monitor that did not actually send the data to the women’s healthcare providers.Using a monitor at home made very little difference to many of the outcomes for mother or baby, although not all studies measured all outcomes. Women using monitors were no less likely to experience preterm birth at less than 37 or 32 weeks of pregnancy (GRADE very low). Women using monitors were less likely to experience preterm birth at less than 34 weeks, but when we analysed only high-quality studies, no clear difference remained (GRADE high). Babies born to women using the monitor were less likely to be admitted to neonatal intensive care (GRADE moderate) but there were no fewer deaths (GRADE low). Women using the monitor were more likely to make an unscheduled antenatal visit (GRADE moderate), but the number of antenatal hospital admissions did not differ (GRADE low). Women using monitors appeared to be more likely to receive tocolysis (treatment to stop labour) (GRADE low), but when we looked only at high-quality studies there was no clear difference. We found no data to assess women's views, although one large trial reported low compliance with monitor use. In some studies, women with monitors had more contact with midwives or maternity nurses, but it is unclear what effect this had. Home uterine monitoring may result in fewer admissions to a neonatal intensive care unit, but more unscheduled antenatal visits and treatment for preterm labour. The level of evidence is generally low to moderate.

10.1002/14651858.CD006172.pub4

cochrane-simplification-train-2286

cochrane-simplification-train-2286

We included 14 parallel-group RCTs and one cross-over RCT with interventions lasting from 8 weeks to 24 months. Of 11 adult studies with 690 participants, six used azithromycin, four roxithromycin, and one erythromycin. Four studies with 190 children used either azithromycin, clarithromycin, erythromycin, or roxithromycin. We included nine adult studies in our comparison between macrolides and placebo and two in our comparison with no intervention. We included one study with children in our comparison between macrolides and placebo and one in our comparison with no intervention. In adults, macrolides reduced exacerbation frequency to a greater extent than placebo (OR 0.34, 95% confidence interval (CI) 0.22 to 0.54; 341 participants; three studies; I2 = 65%; moderate-quality evidence). This translates to a number needed to treat for an additional beneficial outcome of 4 (95% CI 3 to 8). Data show no differences in exacerbation frequency between use of macrolides (OR 0.31, 95% CI 0.08 to 1.15; 43 participants; one study; moderate-quality evidence) and no intervention. Macrolides were also associated with a significantly better quality of life compared with placebo (MD -8.90, 95% CI -13.13 to -4.67; 68 participants; one study; moderate-quality evidence). We found no evidence of a reduction in hospitalisations (OR 0.56, 95% CI 0.19 to 1.62; 151 participants; two studies; I2 = 0%; low-quality evidence), in the number of participants with serious adverse events, including pneumonia, respiratory and non-respiratory infections, haemoptysis, and gastroenteritis (OR 0.49, 95% CI 0.20 to 1.23; 326 participants; three studies; I2 = 0%; low-quality evidence), or in the number experiencing adverse events (OR 0.83, 95% CI 0.51 to 1.35; 435 participants; five studies; I2 = 28%) in adults with macrolides compared with placebo. In children, exacerbation frequency was reduced more with macrolides than with placebo (IRR 0.50, 95% CI 0.35 to 0.71; 89 children; one study; low-quality evidence). However there was no significant difference in this age group with regard to: hospitalisations (OR 0.28, 95% CI 0.07 to 1.11; 89 children; one study; low-quality evidence), serious adverse events, defined within the study as exacerbations of bronchiectasis or investigations related to bronchiectasis (OR 0.43, 95% CI 0.17 to 1.05; 89 children; one study; low-quality evidence), or adverse events (OR 0.78, 95% CI 0.33 to 1.83; 89 children; one study), in those receiving macrolides compared to placebo. The same study reported an increase in macrolide-resistant bacteria (OR 7.13, 95% CI 2.13 to 23.79; 89 children; one study), an increase in resistance to Streptococcus pneumoniae (OR 13.20, 95% CI 1.61 to 108.19; 89 children; one study), and an increase in resistance to Staphylococcus aureus (OR 4.16, 95% CI 1.06 to 16.32; 89 children; one study) with macrolides compared with placebo. Quality of life was not reported in the studies with children. Long-term macrolide therapy may reduce the frequency of exacerbations and improve quality of life, although supporting evidence is derived mainly from studies of azithromycin, rather than other macrolides, and predominantly among adults rather than children. However, macrolides should be used with caution, as limited data indicate an associated increase in microbial resistance. Macrolides are associated with increased risk of cardiovascular death and other serious adverse events in other populations, and available data cannot exclude a similar risk among patients with bronchiectasis.

We found 15 studies that compared macrolides with placebo (a substance or treatment with no benefit) or no intervention. Eleven studies involved 690 adults (aged 18 years and older) and four studies involved 190 children. Among adults, six used azithromycin, four roxithromycin, and one erythromycin. The four studies with children used azithromycin, clarithromycin, erythromycin, or roxithromycin. This review is current to January 2018. The studies on azithromycin reported improved quality of life in adults. We do not have sufficient evidence from other macrolides to make a robust judgement on their use, and we similarly have insufficient evidence from children to draw clear conclusions. Although we found only a few trials, they do show a possible increase in antibiotic resistance. Antibiotic resistance is seen when an antibiotic becomes less effective at killing the bacteria causing the chest infection. We know that macrolides are associated with higher risk of cardiovascular death and other serious adverse events when they are used to treat other conditions. The data in our review suggest it is possible that people with bronchiectasis are at risk for these adverse effects when taking macrolides. Generally the limited number of studies evaluating macrolides and the variation among them indicate that we cannot be sure of the overall effect of their use in bronchiectasis. Further high-quality studies are needed to examine the role of long-term macrolide antibiotics in the treatment of adults and children with bronchiectasis.

10.1002/14651858.CD012406.pub2

cochrane-simplification-train-2287

cochrane-simplification-train-2287

Twelve trials were included in the review. There were seven crossover trials and five parallel group studies. For the comparisons between anticholinergic drugs with tricyclic antidepressants, alpha adrenergic agonists, afferent nerve inhibitors, and calcium channel blocker a single trial was identified for each. Nine trials compared flavoxate with anticholinergics. There was no evidence of a difference in cure rates between anticholinergics and flavoxate. Adverse effects were more frequent in anticholinergic groups versus flavoxate groups (RR 2.28 95% CI 1.45 to 3.56). There was no strong evidence to favour either anticholinergic drugs or the comparators. Many of the drugs considered in trials in this review are no longer used in clinical practice (and this includes the most commonly tested - flavoxate). There is inadequate evidence as to determine whether any of the available druge are better or worse than anticholinergic medications. Larger randomised controlled trials in clinical settings are required to further establish the role of these medications in the management of overactive bladder syndrome.

This review sought evidence to compare other types of drugs with anticholinergics. Only a few, small-scale randomised trials were found, many testing drugs that are no longer used clinically. The review found inadequate evidence to assess whether or not available alternative drugs are better or worse than anticholinergics in the management of people with symptoms of overactive bladder syndrome.

10.1002/14651858.CD003190.pub4

cochrane-simplification-train-2288

cochrane-simplification-train-2288

We included ten studies, with a total of 928 women. All included studies reported outcomes per woman randomised. We assessed no studies as being at low risk of bias across all domains and found that the main limitation was lack of blinding. Using the GRADE method, we determined that the quality of the evidence ranged from moderate to very low, and we identified issues arising from risk of bias, imprecision, and inconsistency. Comparing follicular flushing to aspiration alone revealed probably little or no difference in the live birth rate (OR 0.95, 95% CI 0.58 to 1.56; three RCTs; n = 303; I2 = 30%; moderate-quality evidence). This suggests that with a live birth rate of approximately 41% with aspiration alone, the equivalent live birth rate with follicular flushing is likely to lie between 29% and 52%. None of the included studies reported on the primary outcome of miscarriage rate. Data show probably little or no difference in oocyte yield (MD -0.28 oocytes, 95% CI -0.64 to 0.09; six RCTs; n = 708; I2 = 0%; moderate-quality evidence). Very low-quality evidence suggests that the duration of oocyte retrieval was longer in the follicular flushing group than in the aspiration only group (MD 166.01 seconds, 95% CI 141.96 to 190.06; six RCTs; n = 714; I2 = 88%). We found no evidence of a difference in the total number of embryos per woman randomised (MD -0.10 embryos, 95% CI -0.34 to 0.15; two RCTs; n = 160; I2 = 58%; low-quality evidence) and no evidence of a difference in the number of embryos cryopreserved (meta-analysis not possible). Data show probably little or no difference in the clinical pregnancy rate (OR 1.07, 95% CI 0.78 to 1.46; five RCTs; n = 704; I2 = 49%; moderate-quality evidence). Only two studies reported on adverse outcomes: One reported no differences in patient-reported adverse outcomes (depression, anxiety, and stress), and the other reported no differences in needle blockage, vomiting, and hypotension. No studies reported on safety. This review suggests that follicular flushing probably has little or no effect on live birth rates compared with aspiration alone. None of the included trials reported on effects of follicular aspiration and flushing on the miscarriage rate. Data suggest little or no difference between follicular flushing and aspiration alone with respect to oocyte yield, total embryo number, or number of cryopreserved embryos. In addition, follicular flushing probably makes little or no difference in the clinical pregnancy rate. Evidence was insufficient to allow any firm conclusions with respect to adverse events or safety.

This review included ten research studies that randomly assigned a total of 928 women to follicular aspiration alone or follicular flushing after aspiration. To see if there was a difference between the two techniques, we wanted to look at the main results of live birth rate (number of babies born per 1000 women) and miscarriage rate (number of miscarriages per 1000 women). We carried out a comprehensive search to identify all relevant research in this field available in July 2017. Three studies reported on the main result of live birth rate and noted that follicular flushing probably has little or no effect on live birth rate compared with aspiration alone (moderate-quality evidence). This suggests that if a live birth rate of approximately 41% is seen with aspiration alone, the equivalent live birth rate with follicular flushing is likely to lie between 29% and 52%. None of the included studies reported on the miscarriage rate. Studies also found that follicular flushing probably makes little or no difference in the number of eggs retrieved, the number of embryos, or the clinical pregnancy rate compared with aspiration alone. Although the quality of evidence was very low, it appears that follicular flushing takes much longer to perform than aspiration alone. Evidence was insufficient to permit any firm conclusions with respect to adverse events or safety. More research is needed to find out whether any specific patient groups would benefit from follicular flushing. The quality of evidence for the main outcome of live birth rate was moderate. The quality of evidence for the other outcomes ranged from very low to moderate. The main limitations of included studies were lack of blinding (the process whereby women participating in the trial as well research staff are not aware of the intervention used), inconsistency (differences between different studies), and imprecision (insufficient data).

10.1002/14651858.CD004634.pub3

cochrane-simplification-train-2289

cochrane-simplification-train-2289

We included six studies (916 participants with 988 teeth) reported in English. All the studies had high risk of bias. The six studies examined five different comparisons, including MTA versus intermediate restorative material (IRM), MTA versus super ethoxybenzoic acid cement (Super-EBA), Super-EBA versus IRM, dentine-bonded resin composite versus glass ionomer cement and glass ionomer cement versus amalgam. There was therefore little pooling of data and very little evidence for each comparison. There is weak evidence of little or no difference between MTA and IRM at the first year of follow-up (risk ratio (RR) 1.09; 95% confidence interval (CI): 0.97 to 1.22; 222 teeth; quality of evidence: low). Insufficient evidence of a difference between MTA and IRM on success rate at the second year of follow-up (RR 1.06; 95% CI: 0.89 to 1.25; 86 teeth, 86 participants; quality of evidence: very low). All the other outcomes were based on a single study. There is insufficient evidence of any difference between MTA and Super-EBA at the one-year follow-up (RR 1.03; 95% CI: 0.96 to 1.10; 192 teeth, 192 participants; quality of evidence: very low), and only weak evidence indicating there might be a small increase in success rate at the one-year follow-up in favour of IRM compared to Super-EBA (RR 0.90; 95% CI: 0.80 to 1.01; 194 teeth; quality of evidence: very low). There was also insufficient and weak evidence to show that dentine-bonded resin composite might be a better choice for increasing retrograde filling success rate compared to glass ionomer cement at the one-year follow-up (RR 2.39; 95% CI: 1.60 to 3.59; 122 teeth, 122 participants; quality of evidence: very low). And there was insufficient evidence of a difference between glass ionomer cement and amalgam at both the one-year (RR 0.98; 95% CI: 0.86 to 1.12; 105 teeth; quality of evidence: very low) and five-year follow-ups (RR 1.00; 95% CI: 0.84 to 1.20; 82 teeth; quality of evidence: very low). None of these studies reported an adverse event. Based on the present limited evidence, there is insufficient evidence to draw any conclusion as to the benefits of any one material over another. We conclude that more high-quality RCTs are required.

The evidence in this review, which was carried out together with Cochrane Oral Health, is up-to-date as of 13th September 2016. We included six studies that evaluated 916 participants and 988 teeth, who were undergoing retrograde filling using different types of filling material: mineral trioxide aggregate (MTA), intermediate restorative material (IRM), super ethoxybenzoid acid (Super-EBA), dentine-bonded resin composite, glass ionomer cement, and amalgam. Five studies were conducted in Europe and one in Asia. Studies measured the success rate with clinical or radiological methods. None of the studies reported possible side effects. The limited evidence is insufficient to draw any conclusion as to the benefits of any one material over another, so we are not able to recommend which material is best to use in retrograde filling at present. The evidence presented is of very low quality due to the small amount of available studies, all at high risk of bias, results were imprecise and may not be applicable to other settings/countries.

10.1002/14651858.CD005517.pub2

cochrane-simplification-train-2290

cochrane-simplification-train-2290

We included 14 studies (421 participants) in the analysis. The sensitivities for conversion from MCI to Alzheimer's disease dementia were between 25% and 100% while the specificities were between 15% and 100%. From the summary ROC curve we fitted we estimated that the sensitivity was 76% (95% confidence interval (CI): 53.8 to 89.7) at the included study median specificity of 82%. This equates to a positive likelihood ratio of 4.03 (95% CI: 2.97 to 5.47), and a negative likelihood ratio of 0.34 (95% CI: 0.15 to 0.75). Three studies recruited participants from the same Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort but only the largest ADNI study (Herholz 2011) is included in the meta-analysis. In order to demonstrate whether the choice of ADNI study or discriminating brain region (Chételat 2003) or reader assessment (Pardo 2010) make a difference to the pooled estimate, we performed five additional analyses. At the median specificity of 82%, the estimated sensitivity was between 74% and 76%. There was no impact on our findings. In addition to evaluating Alzheimer's disease dementia, five studies evaluated the accuracy of ¹⁸F-FDG PET for all types of dementia. The sensitivities were between 46% and 95% while the specificities were between 29% and 100%; however, we did not conduct a meta-analysis because of too few studies, and those studies which we had found recruited small numbers of participants. Our findings are based on studies with poor reporting, and the majority of included studies had an unclear risk of bias, mainly for the reference standard and participant selection domains. According to the assessment of Index test domain, more than 50% of studies were of poor methodological quality. It is difficult to determine to what extent the findings from the meta-analysis can be applied to clinical practice. Given the considerable variability of specificity values and lack of defined thresholds for determination of test positivity in the included studies, the current evidence does not support the routine use of ¹⁸F-FDG PET scans in clinical practice in people with MCI. The ¹⁸F-FDG PET scan is a high-cost investigation, and it is therefore important to clearly demonstrate its accuracy and to standardise the process of ¹⁸F-FDG PET diagnostic modality prior to its being widely used. Future studies with more uniform approaches to thresholds, analysis and study conduct may provide a more homogeneous estimate than the one available from the included studies we have identified.

The evidence is current to January 2013. We included 16 studies covering 697 participants with MCI. The studies have been published over a 14-year period (1999 to 2013). Study sizes were small and ranged from 19 to 94 participants. Five papers have a mean age of less than 70 years. The age range in the youngest sample was 55 to 73 years and in the oldest sample was 71 to 86 years. Participants were mainly recruited from university departments, clinics or research centres. The percentage of participants with positive ¹⁸F-FDG PET scans at baseline ranged in the included studies from 10.5% to 74% and the percentage of those participants who converted to Alzheimer’s disease dementia over a period of time ranged from 22% to 50%. Included studies reported a range of different cut-off values used for identifying their participants with positive ¹⁸F-FDG PET scans. Our findings are based on studies with poor reporting. The majority of included studies had an unclear risk of bias, mainly because they did not describe in sufficient details how participants were selected and how the clinical diagnosis of Alzheimer’s disease dementia was justified. According to the assessment of the ¹⁸F-FDG PET test domain, more than 50% of studies were of poor methodological quality. The main limitations of the review are poor reporting in the included studies, a lack of a widely-accepted cut-off value of the ¹⁸F-FDG PET scan in people with MCI, and the marked variation in test accuracy between the included studies. In this review, we have found that the ¹⁸F-FDG PET scan, as a single test, lacks the accuracy to identify those people with MCI who would develop Alzheimer’s disease dementia or other forms of dementia over a period of time. Assuming a typical conversion rate of MCI to Alzheimer’s disease dementia of 38%, the findings indicate that for every 1000 ¹⁸F-FDG PET scans, 174 cases with a negative scan will progress to Alzheimer's disease dementia and 285 with a positive scan will not. Therefore, a positive ¹⁸F-FDG PET scan in people with MCI is of no clinical value in early prediction of developing Alzheimer's disease dementia.

10.1002/14651858.CD010632.pub2

cochrane-simplification-train-2291

cochrane-simplification-train-2291

Two small studies (enrolling a total of 105 participants) met the inclusion criteria. One was a standard cognitive behavioural treatment (CBT) programme for 61 people with pain from spinal cord injury, followed up for three months, and compared with a waiting list. The other was weekly group psychotherapy for 44 people with burning mouth syndrome, compared with a daily placebo tablet. The overall risk of bias was high in both trials. The CBT study assessed participants for pain, disability, mood, and quality of life, with improvement in treatment and control groups. However, there was no more improvement in the treatment group than in the control for any outcome, either post-treatment or at follow-up. The group psychotherapy study only assessed pain, classifying participants by pain severity. There is a lack of evidence on the efficacy and safety of psychological interventions for people with neuropathic pain. There is insufficient evidence of the efficacy and safety of psychological interventions for chronic neuropathic pain. The two available studies show no benefit of treatment over either waiting list or placebo control groups.

Our confidence in the results of the individual trials was limited by several potential biases in how they were conducted. We were not able to analyse the results of the two trials together because the experiences of people with spinal cord injury or burning mouth are too different from each other. On their own, the trials were too small for us to undertake any statistical analysis. However, neither trial found any clear benefit of treatment. We conclude that there is currently no evidence that will help practitioners and patients to decide whether to use these treatments. We discuss what studies are needed.

10.1002/14651858.CD011259.pub2

cochrane-simplification-train-2292

cochrane-simplification-train-2292

One study, including 28 participants was included in the review; the results were described, primarily, in a narrative manner. This study assessed the feasibility of splenectomy using a laparoscopic approach versus open surgery. Given the lack of detail regarding the study methods beyond randomisation, the overall risk of bias for this study was unclear. The study was carried out over a period of 3.5 years, with each participant followed up only until discharge (less than one week after the intervention); it did not assess the majority of the outcomes outlined in this review (including two of the three primary outcomes, frequency of transfusion and quality of life). A total of three serious post-operative adverse events (the review's third primary outcome) were reported in the laparoscopic splenectomy group (one case of atelectasis and two cases of bleeding), compared to two events of atelectasis in the open surgery group; however, there were no significant differences between the groups for either atelectasis, risk ratio (RR) 0.50 (95% confidence interval (CI) 0.05 to 4.90) or for bleeding, RR 5.00 (95% CI 0.26 to 95.61) (very low-quality evidence). In addition, the study also reported three serious cases of intra-operative bleeding in the laparoscopic group which mandated conversion to open surgery, although the difference between groups was not statistically significant, RR 7.00 (95% CI 0.39 to 124.14) (very low-quality evidence). These effect estimates are based on very small numbers and hence are unreliable and imprecise. From this small study, there appeared to be an advantage for the laparoscopic approach, in terms of post-operative hospital stay, although the group difference was not large (median difference of 1.5 days, P = 0.03). The review was unable to find good quality evidence, in the form of randomised controlled studies, regarding the efficacy of splenectomy for treating thalassaemia major or intermedia. The single included study provided little information about the efficacy of splenectomy, and compared open surgery and laparoscopic methods. Further studies need to evaluate the long-term effectiveness of splenectomy and the comparative advantages of surgical methods. Due to a lack of high quality evidence from randomised controlled studies, well-conducted observational studies may be used to answer this question.

One study with a total of 28 participant was included in the review. This study compared two methods of splenectomy - laparoscopic (keyhole) versus an open surgical approach. Study participants were recruited over a period of 3.5 years, but participants were only followed up to the end of their hospital stay (usually less than one week). The study evaluated the two types of surgical methods. Only one of our three primary outcomes were reported, the number of people experiencing major adverse events (bleeding during and after the operation and complete or partial collapse of a lung). However, the amount of information available is not sufficient to draw any reliable conclusions (very-low quality evidence). Hence, we were unable to provide recommendations regarding the use of splenectomy in people with thalassaemia. Appropriate clinical judgement, in view of the various risks and benefits described by other lower quality sources of evidence (e.g. observational studies), may be necessary when considering splenectomy in people with thalassaemia. While we are satisfied that the participants had equal chances of undergoing either type of surgery, there is not enough information on other aspects of the study to make any overall judgement on its quality.

10.1002/14651858.CD010517.pub3

cochrane-simplification-train-2293

cochrane-simplification-train-2293

We identified five studies involving the laxatives lactulose, senna, co-danthramer, misrakasneham, docusate and magnesium hydroxide with liquid paraffin. Overall, the study findings were at an unclear risk of bias. As all five studies compared different laxatives or combinations of laxatives, it was not possible to perform a meta-analysis. There was no evidence on whether individual laxatives were more effective than others or caused fewer adverse effects. This second update found that laxatives were of similar effectiveness but the evidence remains limited due to insufficient data from a few small RCTs. None of the studies evaluated polyethylene glycol or any intervention given rectally. There is a need for more trials to evaluate the effectiveness of laxatives in palliative care populations. Extrapolating findings on the effectiveness of laxatives evaluated in other populations should proceed with caution. This is because of the differences inherent in people receiving palliative care that may impact, in a likely negative way, on the effect of a laxative.

We searched medical databases for clinical trials of the use of laxatives for constipation in people receiving palliative care. Two review authors assessed study quality and extracted data. We identified five studies involving 370 people. The laxatives evaluated were lactulose, senna, co-danthramer combined with poloxamer, docusate and magnesium hydroxide combined with liquid paraffin. Misrakasneham was also evaluated; this is a traditional Indian medicine and is used as a laxative, containing castor oil, ghee, milk and 21 types of herbs. There was no evidence on which laxative provided the best treatment. However, the review was limited as the evidence was from only five small trials and patient preference and cost were under evaluated. Further rigorous, independent trials are needed to evaluate the effectiveness of laxatives.

10.1002/14651858.CD003448.pub4

cochrane-simplification-train-2294

cochrane-simplification-train-2294

With this update, four new studies were identified resulting in a total of six trials including 781 women undergoing monitoring of COH with either TVUS alone or a combination of TVUS and serum estradiol concentration during IVF or ICSI treatment. None of the six studies reported our primary outcome of live birth rate. Pooled data showed no evidence of a difference in clinical pregnancy rate per woman between monitoring with TVUS only and combined monitoring (odds ratio (OR) 1.10; 95% confidence interval (CI) 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). This suggests that compared with women with a 34% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate in women using TVUS only was between 29% and 44%. There was no evidence of a difference between the groups in the reported cases of OHSS (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that compared with women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate in women monitored by TVUSS only was between 2% and 8%. There was no evidence of a difference between the groups in the mean number of oocytes retrieved pre woman (mean difference (MD) 0.32; 95% CI -0.60 to 1.24; five studies; N = 596; I² = 17%; low quality evidence). The evidence was low quality for all comparisons. Limitations included imprecision and potential bias due to unclear randomisation methods, allocation concealment and blinding, as well as differences in treatment protocols. Quality assessment was hampered by the lack of methodological descriptions in several studies. This review update found no evidence from randomised trials to suggest that combined monitoring by TVUS and serum estradiol is more efficacious than monitoring by TVUS alone with regard to clinical pregnancy rates and the incidence of OHSS. The number of oocytes retrieved appeared similar for both monitoring protocols. The data suggest that both these monitoring methods are safe and reliable. However, these results should be interpreted with caution because the overall quality of the evidence was low. Results were compromised by imprecision and poor reporting of study methodology. A combined monitoring protocol including both TVUS and serum estradiol may need to be retained as precautionary good clinical practice and as a confirmatory test in a subset of women to identify those at high risk of OHSS. An economic evaluation of the costs involved with the two methods and the views of the women undergoing cycle monitoring would be welcome.

Study characteristics: we included six randomised controlled trials conducted in the UK, France, Spain, Israel and the US, including 781 women. They compared monitoring with TVUS only versus TVUS plus serum estradiol concentration in women undergoing ovarian hyperstimulation for IVF and ICSI treatment. The evidence was current to May 2014. Key results: none of the six studies reported our primary outcome of live birth rate. Pooled data showed no evidence of a difference in clinical pregnancy rate between monitoring with TVUS only and monitoring with TVUS plus estradiol measurement (odds ratio (OR) 1.10; 95% CI 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). Our findings suggest that compared with women with a 34% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate in women using TVUS only was between 29% and 44%. There was no evidence of a difference in OHSS between the two arms (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that compared with women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate in women monitored by TVUS only was between 2% and 8%. Quality of the evidence: the evidence was of low quality. Limitations included imprecision and potential bias due to unclear randomisation methods, allocation concealment and blinding, as well as differences in the treatment protocols. Quality assessment was hampered by a lack of methodological descriptions in several studies. Two studies reported funding by pharmaceutical companies, whereas the remaining four studies did not report their sources of funding.

10.1002/14651858.CD005289.pub3

cochrane-simplification-train-2295

cochrane-simplification-train-2295

Nineteen trials (1249 participants) were included in the review. Four trials reported using an adequate method of allocation concealment and six trials blinded participants and personnel. Only two electrotherapy modalities (low-level laser therapy (LLLT) and pulsed electromagnetic field therapy (PEMF)) have been compared to placebo. No trial has compared an electrotherapy modality plus manual therapy and exercise to manual therapy and exercise alone. The two main questions of the review were investigated in nine trials. Low quality evidence from one trial (40 participants) indicated that LLLT for six days may result in improvement at six days. Eighty per cent (16/20) of participants reported treatment success with LLLT compared with 10% (2/20) of participants receiving placebo (risk ratio (RR) 8.00, 95% confidence interval (CI) 2.11 to 30.34; absolute risk difference 70%, 95% CI 48% to 92%). No participants in either group reported adverse events. We were uncertain whether PEMF for two weeks improved pain or function more than placebo at two weeks because of the very low quality evidence from one trial (32 participants). Seventy-five per cent (15/20) of participants reported pain relief of 30% or more with PEMF compared with 0% (0/12) of participants receiving placebo (RR 19.19, 95% CI 1.25 to 294.21; absolute risk difference 75%, 95% CI 53% to 97%). Fifty-five per cent (11/20) of participants reported total recovery of joint function with PEMF compared with 0% (0/12) of participants receiving placebo (RR 14.24, 95% CI 0.91 to 221.75; absolute risk difference 55%, 95% CI 31 to 79). Moderate quality evidence from one trial (63 participants) indicated that LLLT plus exercise for eight weeks probably results in greater improvement when measured at the fourth week of treatment, but a similar number of adverse events, compared with placebo plus exercise. The mean pain score at four weeks was 51 points with placebo plus exercise, while with LLLT plus exercise the mean pain score was 32 points on a 100 point scale (mean difference (MD) 19 points, 95% CI 15 to 23; absolute risk difference 19%, 95% CI 15% to 23%). The mean function impairment score was 48 points with placebo plus exercise, while with LLLT plus exercise the mean function impairment score was 36 points on a 100 point scale (MD 12 points, 95% CI 6 to 18; absolute risk difference 12%, 95% CI 6 to 18). Mean active abduction was 70 degrees with placebo plus exercise, while with LLLT plus exercise mean active abduction was 79 degrees (MD 9 degrees, 95% CI 2 to 16; absolute risk difference 5%, 95% CI 1% to 9%). No participants in either group reported adverse events. LLLT's benefits on function were maintained at four months. Based on very low quality evidence from six trials, we were uncertain whether therapeutic ultrasound, PEMF, continuous short wave diathermy, Iodex phonophoresis, a combination of Iodex iontophoresis with continuous short wave diathermy, or a combination of therapeutic ultrasound with transcutaneous electrical nerve stimulation (TENS) were effective adjuncts to exercise. Based on low or very low quality evidence from 12 trials, we were uncertain whether a diverse range of electrotherapy modalities (delivered alone or in combination with manual therapy, exercise, or other active interventions) were more or less effective than other active interventions (for example glucocorticoid injection). Based upon low quality evidence from one trial, LLLT for six days may be more effective than placebo in terms of global treatment success at six days. Based upon moderate quality evidence from one trial, LLLT plus exercise for eight weeks may be more effective than exercise alone in terms of pain up to four weeks, and function up to four months. It is unclear whether PEMF is more or less effective than placebo, or whether other electrotherapy modalities are an effective adjunct to exercise. Further high quality randomised controlled trials are needed to establish the benefits and harms of physical therapy interventions (that comprise electrotherapy modalities, manual therapy and exercise, and are reflective of clinical practice) compared to interventions with evidence of benefit (for example glucocorticoid injection or arthrographic joint distension).

This summary of an updated Cochrane review presents what we know from research about the benefits and harms of electrotherapy modalities in people with frozen shoulder. After searching for all relevant studies published up to May 2014, we included 19 trials (1249 participants). Of the included participants, 61% were women, the average age was 55 years, and the average duration of the condition was 5.5 months. The average duration of delivery of electrotherapy interventions was four weeks. Pain (higher scores mean worse pain) People who received LLLT and exercise had less pain than people who had placebo plus exercise - pain was 19 points less (ranging from 15 to 23 points less) at the fourth week of treatment (19% absolute improvement, ranging from 15% to 23% improvement). - People who had LLLT and exercise rated their pain score as 32 points on a scale of 0 to 100 points. - People who had placebo and exercise rated their pain score as 51 points on a scale of 0 to 100 points. Function impairment (higher scores mean worse function impairment) People who received LLLT and exercise had less function impairment than people who had placebo and exercise - function impairment was 12 points less (ranging from 6 to 18 points less) at the fourth week of treatment (12% absolute improvement, ranging from 6% to 18% improvement). - People who had LLLT and exercise rated their function impairment as 36 points on a scale of 0 to 100 points. - People who had placebo and exercise rated their function impairment as 48 points on a scale of 0 to 100 points. Active shoulder abduction (higher degrees of movement mean greater shoulder abduction) People who received LLLT and exercise had greater active shoulder abduction than people who had placebo and exercise - active shoulder abduction was 9 degrees more (ranging from 2 to 16 degrees more) at the fourth week of treatment (5% absolute improvement, ranging from 1% to 9% improvement). - People who had LLLT and exercise had active shoulder abduction of 79 degrees. - People who had placebo and exercise had active shoulder abduction of 70 degrees. Side effects No person in either group reported any side effects. Participant-reported pain relief of 30% or greater, global assessment of treatment success, and quality of life These were not measured in this trial. There was low quality evidence that LLLT for six days may improve global assessment of treatment success more than placebo, when measured at six days. Further research is likely to change the estimate. We are very uncertain about whether PEMF for two weeks improves pain or function any more than placebo because of the very low quality evidence from one trial. There was moderate quality evidence that LLLT plus exercise for eight weeks may improve pain, up to four weeks, and function, up to four months, more than placebo plus exercise. Further research may change the estimate. We are very uncertain about whether therapeutic ultrasound, PEMF, Iodex phonophoresis, continuous short wave diathermy, a combination of Iodex iontophoresis with continuous short wave diathermy, or a combination of therapeutic ultrasound with transcutaneous electrical nerve stimulation (TENS) are effective adjuncts to exercise.

10.1002/14651858.CD011324

cochrane-simplification-train-2296

cochrane-simplification-train-2296

We identified two studies that met our selection criteria: a controlled interrupted time series study evaluating a regulatory policy involving the monitoring of prescribing of benzodiazepines; and a controlled before‒after study of an educational policing involving mailed educational materials on prescribing for physicians and Health Maintenance Organization (HMO) members as well as an intervention to regulate drug reimbursement. We are uncertain about the effects on medicine use of a regulatory policy involving the monitoring of prescribing with triplicate prescriptions, compared with no regulatory intervention (very low certainty evidence). We are also uncertain about the effects on medicine use, assessed through doctors' prescribing, and costs of an educational policy involving mailed educational materials on prescribing for physicians and HMO members, compared to no educational intervention or an intervention to regulate drug reimbursement (very low certainty evidence). Neither of the included studies measured healthcare utilization, health outcomes, or additional costs, if any, to patients. We are uncertain of the effects of educational or regulatory policies targeting prescribers due to very limited evidence of very low certainty. The impacts of these policies therefore need to be evaluated rigorously using appropriate study designs. Evaluations are needed across a range of settings, including low- and middle-income countries, and across different types of prescribers and medicines.

The review authors found two relevant studies. Both of these studies were from the USA and both assessed policies that were introduced in the late 1990s. The first study assessed a policy that aimed to get doctors to prescribe antihistamines that were cheaper but considered to be just as good as other antihistamines. In one part of the study, letters were sent to doctors and to their patients telling them about the new policy, and giving them information about the antihistamine. In another part of the study, letters were only sent to doctors. The second study assessed a policy that aimed to get doctors to prescribe fewer benzodiazepines to certain types of patients. This policy required doctors in the State of New York to fill in three copies of the same form each time they prescribed benzodiazepines. Pharmacies then sent one of these copies to a state surveillance unit that monitored what doctors were prescribing. The study compared these doctors to doctors in the State of New Jersey, who were not monitored in the same way. Because the evidence from both of these studies was of very low certainty, we do not know what effects these policies had on people’s medicine use. We also do not know whether these policies had any effect on people’s health or their use of healthcare services or on costs because the studies did not measure this. How up to date is this review? The review authors searched for studies that had been published up to March 2018.

10.1002/14651858.CD013478

cochrane-simplification-train-2297

cochrane-simplification-train-2297

We included in the analysis four trials with 495 participants (most with systemic sclerosis). We formed two separate comparisons: cyclophosphamide versus placebo (two trials, 195 participants) and cyclophosphamide versus mycophenolate (two trials, 300 participants). We found evidence to be of low quality, as dropout rates were high in the intervention groups, and as we noted a wide confidence interval around the effect with small differences, which affected the precision of results. The data demonstrates significant improvement in lung function with cyclophosphamide compared with placebo (post-treatment FVC % mean difference (MD) 2.83, 95% confidence interval (CI) 0.80 to 4.87; P = 0.006) but no significant difference in post-treatment DLCO (% MD -1.68, 95% CI -4.37 to 1.02; P = 0.22; two trials, 182 participants). Risk of adverse effects was increased in the cyclophosphamide treatment groups compared with the placebo groups, in particular, haematuria, leukopenia, and nausea, leading to a higher rate of withdrawal from cyclophosphamide treatment. The data demonstrates statistically significant improvement in one-measure of quality of life in one trial favouring cyclophosphamide over placebo and clinically and statistically significant improvement in breathlessness in one trial favouring cyclophosphamide compared with placebo, with no significant impact on mortality. Trialists reported no significant impact on lung function when cyclophosphamide was used compared with mycophenolate at 12 months (FVC % MD -0.82, 95% CI -3.95 to 2.31; P = 0.61; two trials, 149 participants; DLCO % MD -1.41, 95% CI -10.40 to 7.58; P = 0.76; two trials, 149 participants). Risk of side effects was increased with cyclophosphamide versus mycophenolate, in particular, leukopenia and thrombocytopenia. The data demonstrates no significant impact on health-related quality of life, all-cause mortality, dyspnoea, or cough severity in the cyclophosphamide group compared with the mycophenolate group. No trials reported outcomes associated with functional exercise tests. We performed subgroup analysis to determine whether severity of lung function, connective tissue disease diagnosis, or radiological pattern had any impact on outcomes. One trial reported that cyclophosphamide protected against decreased FVC in individuals with worse fibrosis scores, and also showed that cyclophosphamide may be more effective in those with worse lung function. No association could be made between connective tissue disease diagnosis and outcomes. This review, which is based on studies of varying methodological quality, demonstrates that overall, in this population, small benefit may be derived from the use of cyclophosphamide in terms of mean difference in % FVC when compared with placebo, but not of the difference in % DLCO, or when compared with mycophenolate. Modest clinical improvement in dyspnoea may be noted with the use of cyclophosphamide. Clinical practice guidelines should advise clinicians to consider individual patient characteristics and to expect only modest benefit at best in preserving FVC. Clinicians should carefully monitor for adverse effects during treatment and in the years thereafter. Further studies are required to examine the use of cyclophosphamide; they should be adequately powered to compare outcomes within different subgroups, specifically, stratified for extent of pulmonary infiltrates on high-resolution computed tomography (HRCT) and skin involvement in SSc. Studies on other forms of connective tissue disease are needed. Researchers may consider comparing cyclophosphamide (a potent immunosuppressant) versus antifibrotic agents, or comparing both versus placebo, in particular, for those with evidence of rapidly progressive fibrotic disease, who may benefit the most.

We searched for studies up to May 2017, and we included four studies involving a total of 495 people with interstitial lung disease due to connective tissue disease. Some people were given cyclophosphamide, and others were given other drugs or a placebo. We compared these different groups to look for differences. We found some low-quality evidence showing small benefit of using cyclophosphamide compared with placebo in terms of lung function and symptoms of breathlessness. No clear evidence shows that people who took cyclophosphamide had better lung function than people who took a different drug (mycophenolate mofetil). Some people experienced low blood counts, blood in their urine, and nausea. We rated the quality of the evidence using one of the following grades: very low, low, moderate, or high. A rating of very low-quality evidence means that we are uncertain about the results. A rating of high-quality evidence means that we are very certain about the results. For this Cochrane review, we found evidence of low quality. We included randomised controlled trials that were blinded, which means that participants and those people who assessed study results did not know whether participants had received cyclophosphamide or a placebo. However, the trials mostly included people with systemic sclerosis, so these results may not apply to all people with interstitial lung disease with connective tissue disease.

10.1002/14651858.CD010908.pub2

cochrane-simplification-train-2298

cochrane-simplification-train-2298

Seventeen studies were included. Ten were conducted in a school setting, two in universities, and five in workplaces. One study directly measured health outcomes, and all included studies measured travel outcomes. Two cluster randomised controlled trials in the school setting showed either no change in travel mode or mixed results. A randomised controlled trial in the workplace setting, conducted in a pre-selected group who were already contemplating or preparing for active travel, found improved health-related quality of life on some sub scales, and increased walking. Two controlled before-after studies found that school travel interventions increased walking. Other studies were judged to be at high risk of bias. No included studies were conducted in low- or middle-income countries, and no studies measured the social distribution of effects or adverse effects, such as injury. There is insufficient evidence to determine whether organisational travel plans are effective for improving health or changing travel mode. Organisational travel plans should be considered as complex health promotion interventions, with considerable potential to influence community health outcomes depending on the environmental context in which they are introduced. Given the current lack of evidence, organisational travel plans should be implemented in the context of robustly-designed research studies, such as well-designed cluster randomised trials.

This review focuses on travel plans for organisations, such as workplaces or schools. The main reasons for using travel plans are to reduce congestion and to be environmentally friendly, but travel plans are also commonly claimed to improve health. We included 17 studies in this review. One study found that promoting walking in a workplace improved some aspects of health, including mental health, but no other studies directly measured health effects. All 17 studies looked at changes in travel. Although some found that travel plans increased walking, others did not. Overall, there is not enough evidence to know whether travel plans are effective at changing the way people travel, or whether they improve health. Currently, organisational travel plans should be put in place as part of well-designed research studies.

10.1002/14651858.CD005575.pub3

cochrane-simplification-train-2299

cochrane-simplification-train-2299

Four trials of HCV-related cryoglobulinemia fulfiled selection criteria and the review authors included three in quantitative synthesis. All studies were at high risk of bias. No trial addressed the primary outcome of change in sensory impairment. No trial addressed secondary outcomes of change in combined sensory and motor impairment, disability, or electrodiagnostic measures. A single trial of HCV-related mixed cryoglobulinemia treated with pegylated interferon alfa (peginterferon alfa), ribavirin, and rituximab versus peginterferon alfa and ribavirin did not show a significant difference in the number of participants with improvement in neuropathy at 36 months post treatment (risk ratio (RR) 4.00, 95% confidence interval (CI) 0.27 to 59.31, n = 9). One study of interferon alfa (n = 22) and two studies of rituximab (n = 61) provided adverse event data. Severe adverse events were no more common with interferon alfa (RR 7.00, 95% CI 0.38 to 128.02) or rituximab (RR 3.00, 95% CI 0.13 to 67.06) compared to the control group. There is a lack of RCTs and quasi-RCTs addressing the effects of interventions for peripheral neuropathy associated with HCV infection. At present, there is insufficient evidence from RCTs and quasi-RCTs to make evidence-based decisions about treatment.

We found only four trials from this search of the literature. All four trials in this review included participants with peripheral neuropathy and HCV-related cryoglobulinemia. There were no studies of HCV-related non-cryoglobulinemic peripheral neuropathy. Only one trial, in which there were results for 37 participants, reported effects on neuropathy. This study compared 48 weeks of rituximab and antiviral therapy versus antiviral therapy alone. Three trials, two of rituximab and one of interferon alfa (83 participants in total), reported adverse events. One trial of HCV-related cryoglobulinemia treated with rituximab and antiviral therapy versus antiviral therapy alone did not demonstrate any significant difference in the number of participants with improvement in neuropathy at 36 months post treatment. Two studies of rituximab (61 participants) and one of interferon alfa (22 participants) provided information on adverse events. Severe adverse events were no more common with interferon alfa or rituximab compared to the control group. All four trials had problems with their design or implementation that could have affected the results. High-quality studies of HCV-related peripheral neuropathy treatment are lacking. There is not enough evidence to make evidence-based decisions about treatment based on the results of this review. The evidence is current to August 2014.

10.1002/14651858.CD010404.pub2