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cochrane-simplification-train-2500

cochrane-simplification-train-2500

We include one RCT with relevant data on 29 participants in this review. The trial had a parallel design and was double-blind, but blinding procedures were not described. The trial included people who were non-responsive to fluphenazine 20 mg/day administered for 4 weeks. Participants were randomly assigned to continuing treatment with fluphenazine 20 mg/day, increasing the dose to fluphenazine 80 mg/day or switching to haloperidol 20 mg/day for four additional weeks. Data were reported only for 47 out of 58 initially randomised participants. The trial was published in 1993. The fact that only one RCT with a small sample size (N = 29) was included in the analysis limits the quality of the evidence. Overall, no clear difference was found between groups in terms of the three available outcomes: global state (number of participants with clinically relevant response (RR 1.63, 95% CI 0.17 to 15.99, very low quality evidence); general mental state (endpoint score, BPRS total) (MD 2.00, 95% CI −4.20 to 8.20, very low quality evidence); and negative symptoms (endpoint score, SANS) (MD 3.40, 95% CI −12.56 to 19.36). No data were reported for leaving the study early, adverse effects, time in hospital, quality of life, satisfaction with care and functioning. There is extremely limited evidence and no clear conclusions can be drawn. There is an urgent need for further trials in order to determine the optimal treatment strategy for people with schizophrenia who do not respond to their initial antipsychotic treatment.

The Information Specialist of Cochrane Schizophrenia ran an electronic search (up to 30 March 2017) for trials that randomised people with schizophrenia who were not responding to their initial antipsychotic treatment to receive either an increased antipsychotic dose or switch to a different antipsychotic drug. Nine hundred and two records were found and checked by the review authors. Only one trial met the review requirements and provided usable data. Data were reported for the number of participants who responded to treatment, the general mental state of participants at endpoint of the trial and the presence of negative symptoms at endpoint. There were no data available for any other outcome. No clear difference between increasing the dose of the antipsychotic drug and switching to a different antipsychotic was shown. The available evidence was extremely limited and of very low quality. The results of the present review show that there is no good-quality evidence to help clinicians decide between increasing the antipsychotic dose or switching to a different antipsychotic drug for people not responding to their initial antipsychotic treatment. Therefore, no clear conclusions can be drawn. Larger, well-designed trials are needed.

10.1002/14651858.CD011884.pub2

cochrane-simplification-train-2501

cochrane-simplification-train-2501

We found 17 randomised controlled trials of iNO therapy in preterm infants. We grouped these trials post hoc into three categories on the basis of entry criteria: treatment during the first three days of life for impaired oxygenation, routine use in preterm babies along with respiratory support and later treatment for infants at increased risk for bronchopulmonary dysplasia (BPD). We performed no overall analyses. Eight trials providing early rescue treatment for infants on the basis of oxygenation criteria demonstrated no significant effect of iNO on mortality or BPD (typical risk ratio (RR) 0.94, 95% confidence interval (CI) 0.87 to 1.01; 958 infants). Four studies examining routine use of iNO in infants with pulmonary disease reported no significant reduction in death or BPD (typical RR 0.94, 95% CI 0.87 to 1.02; 1924 infants), although this small effect approached significance. Later treatment with iNO based on risk of BPD (three trials) revealed no significant benefit for this outcome in analyses of summary data (typical RR 0.92, 95% CI 0.85 to 1.01; 1075 infants). Investigators found no clear effect of iNO on the frequency of all grades of IVH nor severe IVH. Early rescue treatment was associated with a non-significant 20% increase in severe IVH. We found no effect on the incidence of neurodevelopmental impairment. iNO does not appear to be effective as rescue therapy for the very ill preterm infant. Early routine use of iNO in preterm infants with respiratory disease does not prevent serious brain injury or improve survival without BPD. Later use of iNO to prevent BPD could be effective, but current 95% confidence intervals include no effect; the effect size is likely small (RR 0.92) and requires further study.

Review authors found 17 randomised controlled trials of iNO in the preterm newborn through searches updated until January 2016. These trials studied preterm babies with very different baseline characteristics; therefore, we decided to divide them into three groups: (1) trials of babies treated in the first few days of life with severe lung disease, (2) studies providing treatment after the first few days of life to babies who were at increased risk of chronic lung disease and (3) trials providing routine early treatment for babies who experienced respiratory distress. In none of the three groups of trials did iNO improve survival, and no consistent evidence suggests that iNO decreases lung injury. Studies in group 1 (early rescue treatment) reported a 20% increase in severe bleeding into the brain. This finding was close to statistically significant. The quality of the evidence was moderate to high. This review of studies found that inhaled nitric oxide therapy does not appear to improve the chances of improved outcomes for preterm infants with pulmonary disease. When given to babies who were very ill, iNO did not seem to help and may have contributed to increased risk of intracranial haemorrhage.

10.1002/14651858.CD000509.pub5

cochrane-simplification-train-2502

cochrane-simplification-train-2502

We included in our review three studies (Moy 2015; Tabak 2013; Voncken-Brewster 2015) with a total of 1580 randomised participants. From Voncken-Brewster 2015, we included the subgroup of individuals with a diagnosis of COPD (284 participants) and excluded those at risk of COPD who had not received a diagnosis (1023 participants). As a result, the total population available for analysis included 557 participants; 319 received smart technology to support self-management and 238 received face-to-face verbal/written or digital information and education about self-management. The average age of participants was 64 years. We included more men than women because the sample from one of the studies consisted of war veterans, most of whom were men. These studies measured five of our nine defined outcomes. None of these studies included outcomes such as self-efficacy, cost-effectiveness, functional capacity, lung function, or anxiety and depression. All three studies included our primary outcome - health-related quality of life (HRQoL) as measured by the Clinical COPD Questionnaire (CCQ) or St George's Respiratory Questionnaire (SGRQ). One study reported our other primary outcomes - hospital admissions and acute exacerbations. Two studies included our secondary outcome of physical activity as measured by daily step counts. One study addressed smoking by providing a narrative analysis. Only one study reported adverse events and noted significant differences between groups, with 43 events noted in the intervention group and eight events in the control group (P = 0.001). For studies that measured outcomes at week four, month four, and month six, the effect of smart technology on self-management and subsequent HRQoL in terms of symptoms and health status was significantly better than when participants received face-to-face/digital and/or written support for self-management of COPD (SMD -0.22, 95% confidence interval (CI) -0.40 to -0.03; P = 0.02). The single study that reported HRQoL at 12 months described no significant between-group differences (MD 1.1, 95% CI -2.2 to 4.5; P = 0.50). Also, hospitalisations (logistic regression odds ratio (OR) 1.6, 95% CI 0.8 to 3.2; P = 0.19) and exacerbations (logistic regression OR 1.4, 95% CI 0.7 to 2.8; P = 0.33) did not differ between groups in the single study that reported these outcomes at 12 months. The activity level of people with COPD at week four, month four, and month six was significantly higher when smart technology was used than when face-to-face/digital and/or written support was provided (MD 864.06 daily steps between groups, 95% CI 369.66 to 1358.46; P = 0.0006). The only study that measured activity levels at 12 months reported no significant differences between groups (mean -108, 95% CI -720 to 505; P = 0.73). Participant engagement in this study was not sustained between four and 12 months. The only study that included smoking cessation found no significant treatment effect (OR 1.06, 95%CI 0.43 to 2.66; P = 0.895). Meta-analyses showed no significant heterogeneity between studies (Chi² = 0.39, P = 0.82; I² = 0% and Chi² = 0.01, P = 0.91; I² = 0%, respectively). Although our review suggests that interventions aimed at facilitating, supporting, and sustaining self-managment in people with COPD and delivered via smart technology significantly improved HRQoL and levels of activity up to six months compared with interventions given through face-to-face/digital and/or written support, no firm conclusions can be drawn. This improvement may not be sustained over a long duration. The only included study that measured outcomes up to 12 months highlighted the need to ensure sustained engagement with the technology over time. Limited evidence suggests that using computer and mobile technology for self-management for people with COPD is not harmful and may be more beneficial for some people than for others, for example, those with an interest in using technology may derive greater benefit. The evidence, provided by three studies at high risk of bias, is of poor quality and is insufficient for advising healthcare professionals, service providers, and members of the public with COPD about the health benefits of using smart technology as an effective means of supporting, encouraging, and sustaining self-management. Further research that focuses on outcomes relevant to different stages of COPD is needed. Researchers should provide clear information on how self-management is assessed and should include longitudinal measures that allow comment on behavioural change.

We included in our review 557 participants from three studies; 319 received smart technology to support self-management, and 238 received face-to-face verbal/written or digital information and education about self-management. The average age of participants was 64 years. Our review included more men than women because the sample from one study consisted of war veterans, most of whom were men. Participants used the technology for just four weeks in one study to six months in the second and four months in the third, which also reported data at 12 months. Technology used in these studies included smart phones or PCs. People who received smart technology showed greater improvement in self-management and quality of life and increased physical activity compared with people who received face-to-face/digital and/or written support over a four-week to six-month period. Also, hospital admissions and exacerbations of COPD did not differ between those who used smart technology and those who did not. Only one study provided information about people who stopped smoking and reported no differences between groups. We found only three studies all at high risk of bias - that we could include in this review, and we could conduct analysis on only two of our outcomes (quality of life and increased physical activity). As a result, we think that current information does not show clearly whether smart technology is helpful for people with COPD. We recommend further research of high quality that focuses on outcomes relevant to different stages of COPD. Researchers should be clear about how self-management is assessed, should report standard trial outcomes, particularly cost, and should include follow-up for at least one year so they can provide comments on behavioural change and impact of treatment.

10.1002/14651858.CD011425.pub2

cochrane-simplification-train-2503

cochrane-simplification-train-2503

In this updated review, we identified eight trials as potentially relevant from our searches. Again, only one trial met the inclusion criteria. This trial randomly assigned 146 participants to either a garlic supplement (with 180 mg of allicin content) or a placebo (once daily) for 12 weeks. The trial reported 24 occurrences of the common cold in the garlic intervention group compared with 65 in the placebo group (P value < 0.001), resulting in fewer days of illness in the garlic group compared with the placebo group (111 versus 366). The number of days to recovery from an occurrence of the common cold was similar in both groups (4.63 versus 5.63). Only one trial met the inclusion criteria, therefore limited conclusions can be drawn. The trial relied on self reported episodes of the common cold but was of reasonable quality in terms of randomisation and allocation concealment. Adverse effects included rash and odour. There is insufficient clinical trial evidence regarding the effects of garlic in preventing or treating the common cold. A single trial suggested that garlic may prevent occurrences of the common cold but more studies are needed to validate this finding. Claims of effectiveness appear to rely largely on poor-quality evidence.

The evidence is current to the 7 August 2014. Of the eight studies identified, only one fulfilled the criteria for the review. This study assessed 146 participants over a three-month period. Half the participants took a placebo tablet and half took a garlic tablet during this time. The participants then wrote in a diary when they had symptoms of a cold. The included study found that people who took garlic every day for three months (instead of a placebo) had fewer colds. That is, over the three-month period, there were 24 occurrences of the common cold in the garlic group, compared to 65 in the placebo group. When participants experienced a cold, the length of illness was similar in both groups (4.63 versus 5.63 days). More participants in the garlic group (four) than the placebo group (one) noted a smell when burping, so it is possible that blinding of participants was not adequate. However, other potential biases were well controlled. The only included study is directly relevant to the review question. Although the trial is small, there were enough participants to provide precise, reliable results. There is no evidence that results were selectively reported. However, this was possible as the outcomes do not appear to have been decided in advance. Considering the financial incentive for supplement companies to produce positive trials, it is also possible that trials that showed no effect of garlic were never published. Overall, the quality of the evidence is moderate. Possible side effects in this small trial included odour and a skin rash. More information is needed about the possible side effects of garlic.

10.1002/14651858.CD006206.pub4

cochrane-simplification-train-2504

cochrane-simplification-train-2504

For the treatment of primary dysmenorrhoea there was some evidence of the effectiveness of laparoscopic uterine nerve ablation (LUNA) when compared to a control or no treatment. The comparison between LUNA and laparoscopic presacral neurectomy (LPSN) for primary dysmenorrhoea showed no significant difference in pain relief in the short term; however, long-term LPSN was shown to be significantly more effective than LUNA. For the treatment of secondary dysmenorrhoea six identified RCTs addressed endometriosis and one included women with uterine myomas. The treatment of LUNA combined with surgical treatment of endometrial implants versus surgical treatment of endometriosis alone showed that the addition of LUNA did not aid pain relief. For PSN combined with endometriosis treatment versus endometriosis treatment alone there was an overall difference in pain relief although the data suggests this may be specific to laparoscopy and for midline abdominal pain only. Adverse events were significantly more common for presacral neurectomy; however, the majority were complications such as constipation, which may spontaneously improve. There is insufficient evidence to recommend the use of nerve interruption in the management of dysmenorrhoea, regardless of cause. Future methodologically sound and sufficiently powered RCTs should be undertaken.

The review of trials found there was only limited evidence to support the use of surgery for primary dysmenorrhoea and little evidence for its use in women with endometriosis. No adverse effects were found with UNA but PSN was found to cause treatable constipation. More research is needed.

10.1002/14651858.CD001896.pub2

cochrane-simplification-train-2505

cochrane-simplification-train-2505

We identified 11 trials (862 participants). All trials were in neonatal or paediatric populations. The trials covered only three areas of interest: restrictive versus liberal transfusion triggers (two trials), leukoreduction versus non-leukoreduction (two trials) and standard versus non-standard cardiopulmonary bypass (CPB) prime (seven trials). Owing to the clinical diversity in the participant groups (cyanotic (three trials), acyanotic (four trials) or mixed (four trials)) and the intervention groups, it was not appropriate to pool data in a meta-analysis. No study reported data for all the outcomes of interest to this review. Risk of bias was mixed across the included trials, with only attrition bias being low across all trials. Blinding of study personnel and participants was not always possible, depending on the intervention being used. Five trials (628 participants) reported the primary outcome: 30-day mortality. In three trials (a trial evaluating restrictive and liberal transfusion (125 participants), a trial of cell salvage during CPB (309 participants) and a trial of washed red blood cells during CPB (128 participants)), there was no clear difference in mortality at 30 days between the intervention arms. In two trials comparing standard and non-standard CPB prime, there were no deaths in either randomised group. Long-term mortality was similar between randomised groups in one trial each comparing restrictive and liberal transfusion or standard and non-standard CPB prime. Four trials explored a range of adverse effects following red cell transfusion. Kidney failure was the only adverse event that was significantly different: patients receiving cell salvaged red blood cells during CPB were less likely to have renal failure than patients not exposed to cell salvage (risk ratio (RR) 0.26, 95% confidence interval (CI) 0.09 to 0.79, 1 study, 309 participants). There was insufficient evidence to determine whether there was a difference between transfusion strategies for any other severe adverse events. The duration of mechanical ventilation was measured in seven trials (768 participants). Overall, there was no consistent difference in the duration of mechanical ventilation between the intervention and control arms. The duration of intensive care unit (ICU) stay was measured in six trials (459 participants). There was no clear difference in the duration of ICU stay between the intervention arms in the transfusion trigger and leukoreduction trials. In the standard versus non-standard CPB prime trials, one trial examining the impact of washing transfused bypass prime red blood cells showed no clear difference in duration of ICU stay between the intervention arms, while the trial assessing ultrafiltration of the priming blood showed a shorter duration of ICU stay in the ultrafiltration group. There are only a small number of small and heterogeneous trials so there is insufficient evidence to assess the impact of red cell transfusion on patients with congenital heart disease undergoing cardiac surgery accurately. It is possible that the presence or absence of cyanosis impacts on trial outcomes, which would necessitate different clinical management of two groups. Further adequately powered, specific, high-quality trials are warranted to assess this fully.

We searched scientific sources to identify eligible trials and found 11 studies with 862 participants. We found no trials including adults. The identified studies examined three treatments: two trials compared giving a red blood cell transfusion only when the levels of haemoglobin in the blood fell below a certain concentration (known as a restrictive versus a liberal transfusion trigger); two trials compared whether there was a benefit to removing white blood cells (leukocytes) from the transfused red blood cells and seven trials compared methods used to prepare the fluid for the CPB machine. The trials were different in terms of the age of the participants, the type of heart disease and the exact treatment studied so there was been no opportunity to pool data for analysis. All studies did not report on all outcomes (a measure of a participant's clinical and functional status that is used to assess the effectiveness of a treatment, e.g. death, side effects). Key results Our primary outcome was death within 30 days after surgery. Five trials looked at this outcome and found no clear difference in mortality between the treatment arms. Four trials explored other adverse effects following a red blood cell transfusion. A difference in the number of adverse events was only observed for kidney failure: in one trial (with 309 participants), patients receiving cell salvaged red blood cells during CPB were less likely to have renal failure than patients not exposed to cell salvage. Quality of the evidence This review identified only a few, small studies across three interventions. These studies measured many different aspects of red blood cell transfusion in patients having heart surgery so it is difficult to make accurate conclusions about the benefits or risks of red blood cell transfusion for these patients. More research is needed to allow accurate conclusions. Future studies should be bigger and focus on one aspect of transfusion in a specific type of heart disease.

10.1002/14651858.CD009752.pub2

cochrane-simplification-train-2506

cochrane-simplification-train-2506

Three studies were identified that met the inclusion criteria (Peoples 1982; Robb 1986; Toseland 1997) incorporating data on a total of 116 patients (42 in experimental groups, and 74 in the control groups (usual care 43 and social contact 21, 10 in reality orientation). It was not possible to pool the data from the 3 included studies, either because of the different lengths of treatment or choice of different control treatments, or because the outcome measures were not comparable. Two significant results were found: Peoples 1982 - Validation versus usual care. Behaviour at 6 weeks [MD --5.97, 95% CI (-9.43 to -2.51) P=0.0007, completers analysis] favours validation therapy. Toseland 1997 - Validation versus social contact. Depression at 12 months (MOSES) [MD -4.01, 95% CI (-7.74 to - 0.28) P=0.04, completers analysis] favours validation. There were no statistically significant differences between validation and social contact or between validation and usual therapy. There were no assessments of carers. There is insufficient evidence from randomised trials to allow any conclusion about the efficacy of validation therapy for people with dementia or cognitive impairment.

Three studies were identified that met the inclusion criteria. It was not possible to pool the data from the 3 included studies, either because of the different lengths of treatment or choice of different control treatments, or because the outcome measures were not comparable. Two significant results were found but there were no statistically significant differences between validation and social contact or between validation and usual therapy. There were no assessments of carers. All in all there is insufficient evidence from randomised trials to allow any conclusion about the efficacy of validation therapy for people with dementia or cognitive impairment.

10.1002/14651858.CD001394

cochrane-simplification-train-2507

cochrane-simplification-train-2507

In this review, we included 11 heterogeneous studies with a total number of 1569 MCI patients followed for conversion to dementia. Four studies assessed the role of baseline scores of the MMSE in conversion from MCI to all-cause dementia and eight studies assessed this test in conversion from MCI to Alzheimer´s disease dementia. Only one study provided information about the MMSE and conversion from MCI to vascular dementia. For conversion from MCI to dementia in general, the accuracy of baseline MMSE scores ranged from sensitivities of 23% to 76% and specificities from 40% to 94%. In relationship to conversion from MCI to Alzheimer’s disease dementia, the accuracy of baseline MMSE scores ranged from sensitivities of 27% to 89% and specificities from 32% to 90%. Only one study provided information about conversion from MCI to vascular dementia, presenting a sensitivity of 36% and a specificity of 80% with an incidence of vascular dementia of 6.2%. Although we had planned to explore possible sources of heterogeneity, this was not undertaken due to the scarcity of studies included in our analysis. Our review did not find evidence supporting a substantial role of MMSE as a stand-alone single-administration test in the identification of MCI patients who could develop dementia. Clinicians could prefer to request additional and extensive tests to be sure about the management of these patients. An important aspect to assess in future updates is if conversion to dementia from MCI stages could be predicted better by MMSE changes over time instead of single measurements. It is also important to assess if a set of tests, rather than an isolated one, may be more successful in predicting conversion from MCI to dementia.

Our review assessed the current evidence related to one of those brief tests, the Mini-Mental State Examination (MMSE), in the prediction of decline to dementia in people with cognitive impairments. After an extensive search and analysis of available information, we did not find evidence supporting a substantial role of MMSE as a stand-alone single-administration test in the identification of patients who will convert to dementia in the future.

10.1002/14651858.CD010783.pub2

cochrane-simplification-train-2508

cochrane-simplification-train-2508

We included 10 studies, with 623 participants (900 ears). Interventions included: oil-based treatments (triethanolamine polypeptide, almond oil, benzocaine, chlorobutanol), water-based treatments (docusate sodium, carbamide peroxide, phenazone, choline salicylate, urea peroxide, potassium carbonate), other active comparators (e.g. saline or water alone) and no treatment. Nine of the studies were more than 15 years old. The overall risk of bias across the 10 included studies was low or unclear. Primary outcome: proportion of patients (or ears) with complete clearance of ear wax Six studies (360 participants; 491 ears) contributed quantitative data and were included in our meta-analyses. Active treatment versus no treatment Only one study addressed this comparison. The proportion of ears with complete clearance of ear wax was higher in the active treatment group (22%) compared with the no treatment group (5%) after five days of treatment (risk ratio (RR) 4.09, 95% confidence interval (CI) 1.00 to 16.80); one study; 117 ears; NNTB = 8) (low-quality evidence). Active treatment versus water or saline We found no evidence of a difference in the proportion of patients (or ears) with complete clearance of ear wax when the active treatment group was compared to the water or saline group (RR 1.47, 95% CI 0.79 to 2.75; three studies; 213 participants; 257 ears) (low-quality evidence). Two studies applied drops for five days, but one study only applied the drops for 15 minutes. When we excluded this study in a sensitivity analysis it did not change the result. Water or saline versus no treatment This comparison was only addressed in the single study cited above (active versus no treatment) and there was no evidence of a difference in the proportion of ears with complete wax clearance when comparing water or saline with no treatment after five days of treatment (RR 4.00, 95% CI 0.91 to 17.62; one study; 76 ears) (low-quality evidence). Active treatment A versus active treatment B Several single studies evaluated 'head-to-head' comparisons between two active treatments. We found no evidence to show that one was superior to any other. Subgroup analysis of oil-based active treatments versus non-oil based active treatments We found no evidence of a difference in this outcome when oil-based treatments were compared with non-oil-based active treatments. Primary outcome: adverse effects: discomfort, irritation or pain Only seven studies planned to measure and did report this outcome. Only two (141 participants;176 ears) provided useable data. There was no evidence of a significant difference in the number of adverse effects between the types of ear drops in these two studies. We summarised the remaining five studies narratively. All events were mild and reported in fewer than 30 participants across the seven studies (low-quality evidence). Secondary outcomes Three studies reported 'other' adverse effects (how many studies planned to report these is unclear). The available information was limited and included occasional reports of dizziness, unpleasant smell, tinnitus and hearing loss. No significant differences between groups were reported. There were no emergencies or serious adverse effects reported in any of the 10 studies. There was very limited or no information available on our remaining secondary outcomes. Although a number of studies aimed to evaluate whether or not one type of cerumenolytic is more effective than another, there is no high-quality evidence to allow a firm conclusion to be drawn and the answer remains uncertain. A single study suggests that applying ear drops for five days may result in a greater likelihood of complete wax clearance than no treatment at all. However, we cannot conclude whether one type of active treatment is more effective than another and there was no evidence of a difference in efficacy between oil-based and water-based active treatments. There is no evidence to show that using saline or water alone is better or worse than commercially produced cerumenolytics. Equally, there is also no evidence to show that using saline or water alone is better than no treatment.

In March 2018 we searched for clinical trials where ear drops were used to help soften and remove build up of ear wax in patients' ears. We found and included 10 studies with a total of 623 participants. However, only six of these studies provided data with which we could analyse our primary outcome, the proportion of patients with complete ear wax clearance. These six studies included a total of 360 participants, both children and adults (of all ages), with partial or full blockage of the external ear canal with ear wax. The 10 included studies looked at either oil-based drops (triethanolamine polypeptide, almond oil, benzocaine, chlorobutanol), water-based drops (docusate sodium, carbamide peroxide, phenazone, choline salicylate, urea peroxide, potassium carbonate), saline (salty water) or water alone, or no treatment. Only one study compared using drops with an active ingredient to not using drops at all. The drops may help increase the proportion of ears cleared of wax from 1 in 20 (if you do nothing) to about 1 in 5 (if you use drops). We did not find any evidence that water-based or oil-based drops were any different to saline or water. However, we also did not find any evidence that water or saline were better than doing nothing. Adverse (side) effects were not common. Fewer than 30 patients reported any adverse events when using the drops and these were mild (such as slight irritation or pain, or unpleasant smell). No serious side effects were reported by any participant. We rated the quality of the evidence from studies using four levels: very low, low, moderate or high quality. High-quality evidence means that we are very confident in the results. Very low-quality evidence means that we are very uncertain about the results. For wax clearance, we rated the quality of the evidence as low. For adverse effects we rated the quality of the evidence as low. We have found that using ear drops when you have a partially or completely blocked ear canal may help to remove the ear wax in your ear. It is not clear whether one type of drop is any better than another, or whether drops containing active ingredients are any better than plain or salty water.

10.1002/14651858.CD012171.pub2

cochrane-simplification-train-2509

cochrane-simplification-train-2509

We included 11 trials involving 1069 participants at low anaesthetic risk. The sample size varied from 40 to 300 participants. We included 23 comparisons. All trials were at a high risk of bias. We were unable to perform a meta-analysis because there were no two trials involving the same comparison. Primary outcomes included perioperative mortality, serious morbidity and proportion of patients who were discharged on the same day. There were no perioperative deaths or serious adverse events in either group in the only trial that reported this information (0/60). There was no clear evidence of a difference in the proportion of patients who were discharged on the same day between any of the comparisons. Overall, 472/554 patients (85%) included in this review were discharged as day-procedure laparoscopic cholecystectomy patients. Secondary outcomes included hospital readmissions, health-related quality of life, pain, return to activity and return to work. There was no clear evidence of a difference in hospital readmissions within 30 days in the only comparison in which this outcome was reported. One readmission was reported in the 60 patients (2%) in whom this outcome was assessed. Quality of life was not reported in any of the trials. There was no clear evidence of a difference in the pain intensity, measured by a visual analogue scale, between comparators in the only trial which reported the pain intensity at between four and eight hours after surgery. Times to return to activity and return to work were not reported in any of the trials. There is currently insufficient evidence to conclude that one anaesthetic regimen for day-procedure laparoscopic cholecystectomy is to be preferred over another. However, the data are sparse (that is, there were few trials under each comparison and the trials had few participants) and further well designed randomized trials at low risk of bias and which are powered to measure differences in clinically important outcomes are necessary to determine the optimal anaesthetic regimen for day-procedure laparoscopic cholecystectomy, one of the commonest procedures performed in the western world.

We included 11 trials involving 1069 patients in this review. Most participants in the trials had a low anaesthetic risk. There were no deaths or serious complications in the only trial that reported this information. Overall, 85% of patients (472/554) were discharged as day-procedure laparoscopic cholecystectomy patients and 2% of patients (1/60) required hospital readmission. The reasons for not discharging the patients as day-procedure patients were not described in detail in the trials. The reason for readmission was fever that developed in the patient and which subsequently settled on its own without any treatment. Quality of life was not reported in any of the trials. There was no clear evidence of a difference in the measures of pain intensity between any of the comparisons. Time to return to routine daily activity and to return to work were not reported in any of the trials. There is currently no evidence to support one anaesthetic regimen for day-procedure laparoscopic cholecystectomy over another. All the trials had elements that tended to reduce our trust in the accuracy of the results. Few patients were included in each comparison resulting in a considerable chance of arriving at erroneous conclusions. Randomized controlled trials designed to minimize the risk of arriving at wrong conclusions are necessary to determine the best anaesthetic regimen for day-procedure laparoscopic cholecystectomy, one of the commonest procedures performed in the western world.

10.1002/14651858.CD009784.pub2

cochrane-simplification-train-2510

cochrane-simplification-train-2510

Only four small randomised controlled trials fulfilled the selection criteria. For one of these trials, no data are available for the control group. Two studies compared lavage using diluted surfactant with standard care. Meta-analysis of these two studies did not show a significant effect on mortality (typical relative risk 0.42, 95% confidence interval [CI] 0.12 to 1.46; typical risk difference -0.10, 95% CI -0.24 to 0.04) or the use of ECMO (typical relative risk 0.27, 95% CI 0.04 to 1.86; typical risk difference -0.15, 95% CI -0.35 to 0.04). For the composite outcome of death or use of ECMO, a significant effect favoured the lavage group (typical relative risk 0.33, 95% CI 0.11 to 0.96; typical risk difference -0.19, 95% CI -0.34 to -0.03; number needed to benefit [NNTB] 5). No other benefits were reported. The other published study compared surfactant lavage followed by a surfactant bolus with surfactant bolus therapy alone in MAS complicated by pulmonary hypertension. No significant improvements in mortality, pneumothorax, duration of mechanical ventilation. or duration of hospitalisation were observed. In infants with meconium aspiration syndrome, lung lavage with diluted surfactant may be beneficial, but additional controlled clinical trials of lavage therapy should be conducted to confirm the treatment effect, to refine the method of lavage treatment, and to compare lavage treatment with other approaches, including surfactant bolus therapy. Long-term outcomes should be evaluated in further clinical trials.

This review examined whether cleansing the lung using a natural chemical called surfactant, or another similar fluid, is helpful in MAS. This cleansing procedure is known as lung lavage. Lung lavage with diluted surfactant may help improve the clinical course of infants with MAS, in particular, the likelihood of survival without the need for heart-lung bypass. More trials will be needed to properly evaluate lavage treatment in MAS.

10.1002/14651858.CD003486.pub2

cochrane-simplification-train-2511

cochrane-simplification-train-2511

One hundred and eight randomised trials involving 10,655 participants were included. Ninety-nine different Chinese herbal medicines were tested and compared with placebo (three trials), no intervention (five trials) or conventional medicine (61 trials), or Chinese herbal medicines plus western medicine were compared with western medicine (47 trials). The risk of bias across all studies was unclear for most domains primarily due to inadequate reporting of study design. Although we rated the risk of selective reporting for all studies as unclear, only a few studies contributed numerical data to the key outcomes. Seven trials reported fracture incidence, but they were small in sample size, suffered from various biases and tested different Chinese herbal medicines. These trials compared Kanggusong capsules versus placebo, Kanggusong granule versus Caltrate or ipriflavone plus Caltrate, Yigu capsule plus calcium versus placebo plus calcium, Xianlinggubao capsule plus Caltrate versus placebo plus Caltrate, Bushen Zhuanggu granules plus Caltrate versus placebo granules plus Caltrate, Kanggusong soup plus Caltrate versus Caltrate, Zhuangguqiangjin tablets and Shujinbogu tablets plus calcitonin ampoule versus calcitonin ampoule. The results were inconsistent. One trial showed that Bushenhuoxue therapy plus calcium carbonate tablets and alfacalcidol had a better effect on quality of life score (scale 0 to 100, higher is better) than calcium carbonate tablets and alfacalcidol (mean difference (MD) 5.30; 95% confidence interval (CI) 3.67 to 6.93). Compared with placebo in three separate trials, Chinese herbal medicines (Migu decoction, Bushen Yigu soft extract, Kanggusong capsules) showed a statistically significant increase in bone mineral density (BMD) (e.g. Kanggusong capsules, MD 0.06 g/cm3; 95% CI 0.02 to 0.10). Compared with no intervention in five trials, only two showed that Chinese herbal medicines had a statistically significant effect on increase in BMD (e.g. Shigu yin, MD 0.08 g/cm3; 95% CI 0.03 to 0.13). Compared with conventional medicine in 61 trials, 23 showed that Chinese herbal medicines had a statistically significant effect on increase in BMD. In 48 trials evaluating Chinese herbal medicines plus western medication against western medication, 26 showed better effects of the combination therapy on increase in BMD. No trial reported death or serious adverse events of Chinese herbal medicines, while some trials reported minor adverse effects such as nausea, diarrhoea, etc. Current findings suggest that the beneficial effect of Chinese herbal medicines in improving BMD is still uncertain and more rigorous studies are warranted.

After searching for all relevant studies up to January 2013, we found 108 studies with 10,655 people with osteoporosis. Ninety-nine different Chinese herbal medicines were tested and compared with placebo (three trials), no intervention (five trials) or conventional medicine (61 trials), or Chinese herbal medicines plus conventional medicine were compared with conventional medicine (47 trials). The average length of treatment was 5.7 months (ranging from 3 to 12 months). New fractures: We are uncertain whether Chinese herbal medicines reduce the chance of having a new bone fracture. Seven trials evaluated the incidence of fractures. However, these trials were small and had flaws in their methods. Quality of life: People who took Bushenhuoxue therapy plus calcium carbonate tablets and alfacalcidol rated their quality of life to be 5.30 points better on a scale of 0 to 100 after three months compared to people who did not take the herbal medicine. People who took Bushenhuoxue therapy plus calcium carbonate tablets and alfacalcidol rated their quality of life to be 56.05 on a scale of 0 to 100. People who took calcium carbonate tablets and alfacalcidol rated their quality of life to be 50.75 on a scale of 0 to 100. Serious side effects or deaths: No serious side effects or deaths occurred in the trials. We often do not have precise information about side effects and complications. This is particularly true for rare but serious side effects. Possible side effects may include a mild stomach ache or diarrhoea. Bone mineral density (the amount and type of minerals in the bone): We found studies that compared Chinese herbal medicines with placebo (fake treatment), with no treatment and with conventional medicine. We also found studies that compared Chinese herbal medicines plus conventional medication with just conventional medication. Compared to placebo (fake treatment), three studies showed that bone mineral density increased slightly with Chinese herbal medicines. Compared to no treatment or conventional medicine, some studies showed an increase in bone mineral density with Chinese herbal medicines while others did not. When Chinese herbal medicines plus conventional medication was compared with just conventional medicine, some studies showed an increase in bone mineral density while others did not. In people with osteoporosis: - Chinese herbal medicines may improve bone mineral density and quality of life slightly. Further research is likely to change this estimate of how Chinese herbal medicines affect bone mineral density and quality of life. - We are uncertain whether Chinese herbal medicines reduce the chance of having a new bone fracture. - No trial reported death or serious side effects.

10.1002/14651858.CD005467.pub2

cochrane-simplification-train-2512

cochrane-simplification-train-2512

We identified nine RCTs that met the inclusion criteria, but four were ongoing trials, and were not included in this analysis. We included five RCTs, with 8373 participants, in the NMA (two RCTs compared apixaban to a vitamin K antagonist, two RCTs compared rivaroxaban to a vitamin K antagonist, and one RCT compared dabigatran to a vitamin K antagonist). Very low- to moderate-certainty evidence suggests little or no difference between NOACs and vitamin K antagonists in death from cardiovascular causes (not reported in the dabigatran trial), myocardial infarction, stroke, death from any cause, and stent thrombosis. Apixaban (RR 0.85, 95% CI 0.77 to 0.95), high dose rivaroxaban (RR 0.86, 95% CI 0.74 to 1.00), and low dose rivaroxaban (RR 0.80, 95% CI 0.68 to 0.92) probably reduce the risk of recurrent hospitalisation compared with vitamin K antagonists. No studies looked at health-related quality of life. Very low- to moderate-certainty evidence suggests that NOACs may be safer than vitamin K antagonists in terms of bleeding. Both high dose dabigatran (RR 0.53, 95% CI 0.29 to 0.97), and low dose dabigatran (RR 0.38, 95% CI 0.21 to 0.70) may reduce major bleeding more than vitamin K antagonists. High dose dabigatran (RR 0.83, 95% CI 0.72 to 0.96), low dose dabigatran (RR 0.66, 95% CI 0.58 to 0.75), apixaban (RR 0,67 , 95% Cl 0.51 to 0.88), high dose rivaroxaban (RR 0.66, 95% CI 0.52 to 0.83), and low dose rivaroxaban (RR 0.71, 95% CI 0.57 to 0.88) probably reduce non-major bleeding more than vitamin K antagonists. The results from the NMA were inconclusive between the different NOACs for all primary and secondary outcomes. Very low- to moderate-certainty evidence suggests no meaningful difference in efficacy outcomes between non-vitamin K antagonist oral anticoagulants (NOAC) and vitamin K antagonists following percutaneous coronary interventions (PCI) in people with non-valvular atrial fibrillation. NOACs probably reduce the risk of recurrent hospitalisation for adverse events compared with vitamin K antagonists. Low- to moderate-certainty evidence suggests that dabigatran may reduce the rates of major and non-major bleeding, and apixaban and rivaroxaban probably reduce the rates of non-major bleeding compared with vitamin K antagonists. Our network meta-analysis did not show superiority of one NOAC over another for any of the outcomes. Head to head trials, directly comparing NOACs against each other, are required to provide more certain evidence.

We identified nine studies that compared NOACs with warfarin, four of which were ongoing studies. We included five trials involving 8373 participants in this review. Evidence is current to February 2019. There may be little or no difference in effect between NOACs and warfarin in people with atrial fibrillation, who underwent heart vessel stenting. However, NOACs probably reduce the need for hospitalisation compared to warfarin. NOACs may be safer than warfarin. One of NOACs drugs (dabigatran) may reduce the rate of both major and non-major bleeding. Other NOAC drugs (apixaban and rivaroxaban) probably reduce the rate of non-major bleeding. There was no significant difference between NOACs agents in any primary or secondary outcomes. The evidence ranged from Very low- to moderate-certainty, indicating the need for more research on this issue.

10.1002/14651858.CD013252.pub2

cochrane-simplification-train-2513

cochrane-simplification-train-2513

We identified 56 eligible trials (3781 randomised participants). Eighteen trials did not report the primary outcomes of subjective cure, improvement of SUI or incontinence-specific quality of life (QoL). The risk of bias was generally unclear, as most trials provided little detail when reporting their methods. We assessed 25% of the included trials as being at high risk of bias for a variety of reasons, including industry funding and baseline differences between groups. We did not identify any economic evaluations. For subjective cure of SUI, we found moderate-quality evidence that ES is probably better than no active treatment (risk ratio (RR) 2.31, 95% CI 1.06 to 5.02). We found a similar result for cure or improvement of SUI (RR 1.73, 95% CI 1.41 to 2.11), but the quality of evidence was lower. We are very uncertain if there is a difference between ES and sham treatment in terms of subjective cure because of the very low quality of evidence (RR 2.21, 95% CI 0.38 to 12.73). For subjective cure or improvement, ES may be better than sham treatment (RR 2.03, 95% CI 1.02 to 4.07). The effect estimate was 660/1000 women cured/improved with ES compared to 382/1000 with no active treatment (95% CI 538 to 805 women); and for sham treatment, 402/1000 women cured/improved with ES compared to 198/1000 with sham treatment (95% CI 202 to 805 women). Low-quality evidence suggests that there may be no difference in cure or improvement for ES versus PFMT (RR 0.85, 95% CI 0.70 to 1.03), PFMT plus ES versus PFMT alone (RR 1.10, 95% CI 0.95 to 1.28) or ES versus vaginal cones (RR 1.09, 95% CI 0.97 to 1.21). Electrical stimulation probably improves incontinence-specific QoL compared to no treatment (moderate quality evidence) but there may be little or no difference between electrical stimulation and PFMT (low quality evidence). It is uncertain whether adding electrical stimulation to PFMT makes any difference in terms of quality of life, compared with PFMT alone (very low quality evidence). There may be little or no difference between electrical stimulation and vaginal cones in improving incontinence-specific QoL (low quality evidence). The impact of electrical stimulation on subjective cure/improvement and incontinence-specific QoL, compared with vaginal cones, PFMT plus vaginal cones, or drugs therapy, is uncertain (very low quality evidence). In terms of subjective cure/improvement and incontinence-specific QoL, the available evidence comparing ES versus drug therapy or PFMT plus vaginal cones was very low quality and inconclusive. Similarly, comparisons of different types of ES to each other and of ES plus surgery to surgery are also inconclusive in terms of subjective cure/improvement and incontinence-specific QoL (very low-quality evidence). Adverse effects were rare: in total nine of the women treated with ES in the trials reported an adverse effect. We identified insufficient evidence to compare the risk of adverse effects in women treated with ES compared to any other treatment. We were unable to identify any economic data. The current evidence base indicated that electrical stimulation is probably more effective than no active or sham treatment, but it is not possible to say whether ES is similar to PFMT or other active treatments in effectiveness or not. Overall, the quality of the evidence was too low to provide reliable results. Without sufficiently powered trials measuring clinically important outcomes, such as subjective assessment of urinary incontinence, we cannot draw robust conclusions about the overall effectiveness or cost-effectiveness of electrical stimulation for stress urinary incontinence in women.

We found 56 trials (involving a total of 3781 women, all with stress urinary incontinence but some with urgency urinary incontinence as well) comparing electrical stimulation to no treatment or to any other available treatment. For cure or improvement of SUI, electrical stimulation was probably better than no active or sham treatment. There was not enough evidence to say whether it was any better than pelvic floor muscle training for curing or improving SUI, or for quality of life. Adding electrical stimulation to pelvic floor muscle training may not make much difference to cure or improvement of SUI. It is uncertain whether it offers any improvement in quality of life compared with pelvic floor muscle training. We found that few women reported adverse effects with electrical stimulation, but there was not enough reliable evidence comparing electrical stimulation to other treatments to know more about its safety. There was not enough evidence comparing electrical stimulation to other existing treatments such as drug therapy, pelvic floor muscle training plus vaginal cones, surgery, or different forms of electrical stimulation, to provide evidence-based guidance on which would be better, and for which women, in curing or improving SUI or in improving quality of life. There was no information from these studies to judge value for money. There is some evidence to support the use of electrical stimulation for stress urinary incontinence in women, but we are still very uncertain about the full potential of this treatment because of the low quality of the existing evidence. While we found evidence indicating that electrical stimulation may be better than no treatment, we did not find enough well-designed trials with enough women to fully answer our review questions, so we do not yet know if ES is better or worse than other treatments.

10.1002/14651858.CD012390.pub2

cochrane-simplification-train-2514

cochrane-simplification-train-2514

We included 44 trials in the review with 1809 participants comparing an intervention with a placebo or a control. The age of participants ranged from 17 to 77 years. Most of the trials reported on short-term follow-up (ranging from one week to four weeks). Only one trial reported long-term follow-up (three months). Three studies were at low overall risk of bias, 16 at high overall risk of bias, and the remaining 25 at unclear overall risk of bias. We compared different types of interventions which were categorised as mechanical debridement, chewing gums, systemic deodorising agents, topical agents, toothpastes, mouthrinse/mouthwash, tablets, and combination methods. Mechanical debridement: for mechanical tongue cleaning versus no tongue cleaning, the evidence was very uncertain for the outcome dentist-reported organoleptic test (OLT) scores (MD -0.20, 95% CI -0.34 to -0.07; 2 trials, 46 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Chewing gums: for 0.6% eucalyptus chewing gum versus placebo chewing gum, the evidence was very uncertain for the outcome dentist-reported OLT scores (MD -0.10, 95% CI -0.31 to 0.11; 1 trial, 65 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Systemic deodorising agents: for 1000 mg champignon versus placebo, the evidence was very uncertain for the outcome patient-reported visual analogue scale (VAS) scores (MD -1.07, 95% CI -14.51 to 12.37; 1 trial, 40 participants; very low-certainty evidence). No data were reported for dentist-reported OLT score or adverse events. Topical agents: for hinokitiol gel versus placebo gel, the evidence was very uncertain for the outcome dentist-reported OLT scores (MD -0.27, 95% CI -1.26 to 0.72; 1 trial, 18 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Toothpastes: for 0.3% triclosan toothpaste versus control toothpaste, the evidence was very uncertain for the outcome dentist-reported OLT scores (MD -3.48, 95% CI -3.77 to -3.19; 1 trial, 81 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Mouthrinse/mouthwash: for mouthwash containing chlorhexidine and zinc acetate versus placebo mouthwash, the evidence was very uncertain for the outcome dentist-reported OLT scores (MD -0.20, 95% CI -0.58 to 0.18; 1 trial, 44 participants; very low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. Tablets: no data were reported on key outcomes for this comparison. Combination methods: for brushing plus cetylpyridium mouthwash versus brushing, the evidence was uncertain for the outcome dentist-reported OLT scores (MD -0.48, 95% CI -0.72 to -0.24; 1 trial, 70 participants; low-certainty evidence). No data were reported for patient-reported OLT score or adverse events. We found low- to very low-certainty evidence to support the effectiveness of interventions for managing halitosis compared to placebo or control for the OLT and patient-reported outcomes tested. We were unable to draw any conclusions regarding the superiority of any intervention or concentration. Well-planned RCTs need to be conducted by standardising the interventions and concentrations.

This review is up-to-date as of 8 April 2019. The review includes 44 studies involving 1809 people who were 17 to 77 years old. The review compared an intervention with another intervention, a placebo or a control. It looked at eight different ways to control bad breath: mechanical cleaning (e.g. tongue cleaners and toothbrushes), chewing gums, systemic deodorising agents (e.g. mushroom extract that you eat), topical agents (e.g. gel that you apply), toothpastes, mouthrinse/mouthwash, tablets, and combination of different treatments. The evidence was very uncertain for mechanical tongue cleaning versus no tongue cleaning, 0.6% eucalyptus chewing gum versus placebo chewing gum, 1000 mg mushroom extract versus placebo, hinokitiol gel versus placebo gel, 0.3% triclosan toothpaste versus control toothpaste, mouthwash containing chlorhexidine and zinc acetate versus placebo mouthwash, and brushing plus cetylpyridium mouthwash versus brushing. Harmful effects of the different interventions were not reported or were not important. The level of certainty we have in these findings is low to very low. This was due mainly to risk of bias and the small number of people studied in the included trials. We do not have enough evidence to say which intervention works better to control bad breath.

10.1002/14651858.CD012213.pub2

cochrane-simplification-train-2515

cochrane-simplification-train-2515

We included eight trials with 15,445 participants randomised. The largest trial with 14,641 participants provided data on our primary outcomes. Seven trials reported on CVD risk factors. Three of the eight trials were regarded at high risk of bias for either reporting or attrition bias, most of the 'Risk of bias' domains for the remaining trials were judged as unclear, with the exception of the largest trial where most domains were judged to be at low risk of bias. The composite endpoint, major CVD events was not different between the vitamin C and placebo group (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.89 to 1.10; 1 study; 14,641 participants; low-quality evidence) in the Physicians Health Study II over eight years of follow-up. Similar results were obtained for all-cause mortality HR 1.07, 95% CI 0.97 to 1.18; 1 study; 14,641 participants; very low-quality evidence, total myocardial infarction (MI) (fatal and non-fatal) HR 1.04 (95% CI 0.87 to 1.24); 1 study; 14,641 participants; low-quality evidence, total stroke (fatal and non-fatal) HR 0.89 (95% CI 0.74 to 1.07); 1 study; 14,641 participants; low-quality evidence, CVD mortality HR 1.02 (95% 0.85 to 1.22); 1 study; 14,641 participants; very low-quality evidence, self-reported coronary artery bypass grafting (CABG)/percutaneous transluminal coronary angioplasty (PTCA) HR 0.96 (95% CI 0.86 to 1.07); 1 study; 14,641 participants; low-quality evidence, self-reported angina HR 0.93 (95% CI 0.84 to 1.03); 1 study; 14,641 participants; low-quality evidence. The evidence for the majority of primary outcomes was downgraded (low quality) because of indirectness and imprecision. For all-cause mortality and CVD mortality, the evidence was very low because more factors affected the directness of the evidence and because of inconsistency. Four studies did not state sources of funding, two studies declared non-commercial funding and two studies declared both commercial and non-commercial funding. Currently, there is no evidence to suggest that vitamin C supplementation reduces the risk of CVD in healthy participants and those at increased risk of CVD, but current evidence is limited to one trial of middle-aged and older male physicians from the USA. There is limited low- and very low-quality evidence currently on the effect of vitamin C supplementation and risk of CVD risk factors.

We searched scientific databases for randomised controlled trials (clinical trials where people are allocated at random to one of two or more treatments) looking at the effects of vitamin C supplementation in healthy adults or those at high risk of developing CVD. We did not include people who already had CVD (e.g. heart attacks and strokes). The evidence is current to May 2016. Eight trials fulfilled our inclusion criteria. One large trial looked at the effects of vitamin C supplements on the risk of major CVD events (fatal and non-fatal) and found no beneficial effects. This trial was however conducted in middle-aged and older male doctors in the USA and so its not certain that the effects are the same in other groups of people. Seven trials looked at the effects of vitamin C supplements on CVD risk factors. We could not combine these trials as there was lots of missing information and differences between the trials in terms of the participants recruited, the dose of vitamin C and the duration of trials. Overall, there were inconsistent effects of vitamin C supplements on lipid levels and blood pressure and more research is needed. Four of the included studies did not mention sources of funding of the study, two had non-commercial (grants) funding and two had both commercial (industries) and non-commercial funding (grants). The evidence was of low or very low quality for major CVD events (myocardial infraction, stroke, angina and coronary artery bypass grafting), all-cause mortality and CVD mortality. The evidence was of low quality because it was not applicable to the general population (included only USA male physicians) and limited studies of vitamin C on the prevention of CVD.

10.1002/14651858.CD011114.pub2

cochrane-simplification-train-2516

cochrane-simplification-train-2516

Eighty-two studies met the inclusion criteria. These showed considerable diversity in the targeted health issue and the aims, content, and outcomes of interventions. The majority were conducted in high income countries (n = 55) but many of these focused on low income and minority populations. The diversity of included studies limited meta-analysis to outcomes for four study groups. These analyses found evidence of moderate quality of the effectiveness of LHWs in promoting immunisation childhood uptake (RR 1.22, 95% CI 1.10 to 1.37; P = 0.0004); promoting initiation of breastfeeding (RR = 1.36, 95% CI 1.14 to 1.61; P < 0.00001), any breastfeeding (RR 1.24, 95% CI 1.10 to 1.39; P = 0.0004), and exclusive breastfeeding (RR 2.78, 95% CI 1.74 to 4.44; P <0.0001); and improving pulmonary TB cure rates (RR 1.22 (95% CI 1.13 to 1.31) P <0.0001), when compared to usual care. There was moderate quality evidence that LHW support had little or no effect on TB preventive treatment completion (RR 1.00, 95% CI 0.92 to 1.09; P = 0.99). There was also low quality evidence that LHWs may reduce child morbidity (RR 0.86, 95% CI 0.75 to 0.99; P = 0.03) and child (RR 0.75, 95% CI 0.55 to 1.03; P = 0.07) and neonatal (RR 0.76, 95% CI 0.57 to 1.02; P = 0.07) mortality, and increase the likelihood of seeking care for childhood illness (RR 1.33, 95% CI 0.86 to 2.05; P = 0.20). For other health issues, the evidence is insufficient to draw conclusions regarding effectiveness, or to enable the identification of specific LHW training or intervention strategies likely to be most effective. LHWs provide promising benefits in promoting immunisation uptake and breastfeeding, improving TB treatment outcomes, and reducing child morbidity and mortality when compared to usual care. For other health issues, evidence is insufficient to draw conclusions about the effects of LHWs.

A lay health worker is a member of the community who has received some training to promote health or to carry out some healthcare services, but is not a healthcare professional. In the studies in this review, lay health workers carried out different tasks. These included giving help and advice about issues such as child health, child illnesses, and medicine taking. In some studies, lay health workers also treated people for particular health problems. The studies took place in different settings. In many of the studies, lay health workers worked among people on low incomes in wealthy countries, or among people living in poor countries. What the research says The use of lay health workers, compared to usual healthcare services: - probably leads to an increase in the number of women who start to breastfeed their child; who breastfeed their child at all; and who feed their child with breastmilk only; - probably leads to an increase in the number of children who have their immunization schedule up to date; - may lead to slightly fewer children who suffer from fever, diarrhoea and pneumonia; - may lead to fewer deaths among children under five; - may increase the number of parents who seek help for their sick child. The use of lay health workers, compared to people helping themselves or going to a clinic: - probably leads to an increase in the number of people with tuberculosis who are cured; - probably makes little or no difference in the number of people who complete preventive treatment for tuberculosis.

10.1002/14651858.CD004015.pub3

cochrane-simplification-train-2517

cochrane-simplification-train-2517

IPD were available for 595 participants out of 1102 eligible individuals, from four out of 11 trials (i.e. 54% of the potential data). For remission outcomes, a HR greater than 1 indicates an advantage for phenytoin; and for first seizure and withdrawal outcomes, a HR greater than 1 indicates an advantage for carbamazepine. Most participants included in analysis (78%) were classified as experiencing focal onset seizures at baseline and only 22% were classified as experiencing generalised onset seizures; the results of this review are therefore mainly applicable to individuals with focal onset seizures. Results for the primary outcome of the review were: time to treatment failure for any reason related to treatment (pooled HR adjusted for seizure type for 546 participants: 0.94, 95% CI 0.70 to 1.26, moderate-certainty evidence); time to treatment failure due to lack of efficacy (pooled HR adjusted for seizure type for 546 participants: 0.99, 95% CI 0.69 to 1.41, moderate-certainty evidence); both showing no clear difference between the drugs and time to treatment failure due to adverse events (pooled HR adjusted for seizure type for 546 participants: 1.27, 95% CI 0.87 to 1.86, moderate-certainty evidence), showing that treatment failure due to adverse events may occur earlier on carbamazepine than phenytoin, but we cannot rule out a slight advantage to carbamazepine or no difference between the drugs. For our secondary outcomes (pooled HRs adjusted for seizure type), we did not find any clear differences between carbamazepine and phenytoin: time to first seizure post-randomisation (582 participants): 1.15, 95% CI 0.94 to 1.40, moderate-certainty evidence); time to 12-month remission (551 participants): 1.00, 95% CI 0.79 to 1.26, moderate-certainty evidence); and time to six-month remission (551 participants): 0.90, 95% CI 0.73 to 1.12, moderate-certainty evidence). For all outcomes, results for individuals with focal onset seizures were similar to overall results (moderate-certainty evidence), and results for the small subgroup of individuals with generalised onset seizures were imprecise, so we cannot rule out an advantage to either drug, or no difference between drugs (low-certainty evidence). There was also evidence that misclassification of seizure type may have confounded the results of this review, particularly for the outcome 'time to treatment failure'. Heterogeneity was present in analysis of 'time to first seizure' for individuals with generalised onset seizures, which could not be explained by subgroup analysis or sensitivity analyses. Limited information was available about adverse events in the trials and we could not compare the rates of adverse events between carbamazepine and phenytoin. Some adverse events reported on both drugs were abdominal pain, nausea, and vomiting, drowsiness, motor and cognitive disturbances, dysmorphic side effects (such as rash). Moderate-certainty evidence provided by this systematic review does not show any differences between carbamazepine and phenytoin in terms of effectiveness (retention) or efficacy (seizure recurrence and seizure remission) for individuals with focal onset or generalised onset seizures. However, some of the trials contributing to the analyses had methodological inadequacies and inconsistencies, which may have had an impact on the results of this review. We therefore do not suggest that results of this review alone should form the basis of a treatment choice for a person with newly-onset seizures. We did not find any evidence to support or refute current treatment policies. We implore that future trials be designed to the highest quality possible, with consideration of masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results.

For this updated review, we looked at the evidence from 11 randomised controlled clinical trials comparing phenytoin and carbamazepine, based on how effective the drugs were at controlling seizures (i.e. whether people went back to having seizures or had long periods of freedom from seizures (remission)), and how tolerable any related side effects of the drugs were. Methods We were able to combine data for 595 people from four of the 11 trials; for the remaining 507 people from seven trials, information was not available to use in this review. The evidence is current to August 2018. Key results This review of trials found no difference between these two drugs for the seizure types studied for the outcomes of treatment failure (withdrawal from treatment for any reason and also withdrawal from treatment due to continuing seizures or due to side effects) and controlling seizures (recurrence of seizures or achievement of a seizure-free period (remission) of six months or 12 months). Three-quarters of the people recruited in the four trials had focal onset seizures and only one quarter of the people recruited in the four trials had generalised onset seizures, so the results of this review mainly apply to people with focal onset seizures and the results are very limited for people with generalised onset seizures. More information is needed for people with generalised onset seizures. Some side effects reported by people taking carbamazepine and people taking phenytoin were abdominal pain, nausea, vomiting, tiredness, motor problems (such as poor co-ordination), cognitive problems (poor memory), rashes and other skin problems. Certainty of the evidence We judged the certainty of the evidence as moderate to low for the evidence of treatment failure, moderate for remission outcomes and low for seizure outcomes, as it is likely that misclassification of seizure type influenced the results of the review. Within two of the trials providing data for this review, the design of the trial meant that the people and treating clinicians knew which medication they were taking. This design may have influenced the results. Some of the trials contributing data to the review had methodological problems, which may have introduced bias and inconsistent results into this review, and some individuals over the age of 30 with newly-diagnosed generalised onset seizures may have had their seizure type wrongly diagnosed. These problems may have affected the results of this review and we judged the certainty of the evidence provided by this review as moderate for people with focal onset seizures and of low certainty for people with generalised onset seizures. We do not suggest using the results of this review alone for making a choice between carbamazepine or phenytoin for the treatment of epilepsy. We suggest that all future trials comparing these drugs or any other antiepileptic drugs should be designed using high-quality methods, and that the seizure types of people included in trials should be classified very carefully to ensure results are also of high quality.

10.1002/14651858.CD001911.pub4

cochrane-simplification-train-2518

cochrane-simplification-train-2518

The review included 14 RCTs involving 675 participants, covering a wide range of interventions. Eleven of the included trials assessed participants in clinical stages IA to IIB only. Internal validity was considerably low in studies with a high or unclear risk of bias. The main reasons for this were low methodological quality or missing data, even after we contacted the study authors, and a mean dropout rate of 26% (0% to 72%). Study size was generally small with a minimum of 4 and a maximum of 103 participants. Only one study provided a long enough follow-up for reliable survival analysis. Included studies assessed topical treatments, such as imiquimod, peldesine, hypericin, nitrogen mustard, as well as intralesional injections of interferon-α (IFN-α). The light therapies investigated included psoralen plus ultraviolet A light (PUVA), extracorporeal photopheresis (photochemotherapy), and visible light. Oral treatments included acitretin, bexarotene, and methotrexate. Treatment with parenteral systemic agents consisted of denileukin diftitox; a combination of chemotherapy and electron beam radiation; and intramuscular injections of active transfer factor. Nine studies evaluated therapies by using an active comparator; five were placebo-controlled RCTs. Twelve studies reported on common adverse effects, while only two assessed quality of life. None of these studies compared the health-related quality of life of participants undergoing different treatments. Most of the reported adverse effects were attributed to the interventions. Systemic treatments, and here in particular a combined therapeutic regimen of chemotherapy and electron beam, bexarotene, or denileukin diftitox, showed more adverse effects than topical or skin-directed treatments. In the included studies, clearance rates ranged from 0% to 83%, and improvement ranged from 0% to 88%. The meta-analysis combining the results of 2 trials comparing the effect of IFN-α and PUVA versus PUVA alone showed no significant difference in the relative risk of clearance: 1.07 (95% confidence interval 0.87 to 1.31). None of the included studies demonstrated a significant increase in disease-free intervals, relapse, or overall survival. This review identified trial evidence for a range of different topical and systemic interventions for mycosis fungoides. Because of substantial heterogeneity in design, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be established on the basis of the included RCTs. Taking into account the possible serious adverse effects and the limited availability of efficacy data, topical and skin-directed treatments are recommended first, especially in the early stages of disease. More aggressive therapeutic regimens may show improvement or clearance of lesions, but they also result in more adverse effects; therefore, they are to be considered with caution. Larger studies with comparable, clearly-defined end points for all stages of mycosis fungoides, and a focus on safety, quality of life, and duration of remission as part of the outcome measures, are necessary.

We found 14 studies with a total of 30 publications with 675 participants. Most of the studies (8) had fewer than 50 participants and lasted less than 12 months. None of these studies compared the quality of life of participants with regard to different treatments. Also, no study compared a particular therapy to a "wait and see" strategy. Most of the studies described adverse effects, from mild symptoms to severe life-threatening or even lethal complications depending upon the type of treatment. More aggressive treatment options like systemic chemotherapy showed more adverse effects than topical therapies that are applied directly to the skin. None of the trials reported a long-term benefit (i.e. clearance of all symptoms of disease lasting at least two years). Therefore, the conclusions from these studies should be treated with caution. Treatment of mycosis fungoides should be based on the stage of progression of the disease with a focus on the limitations of severe adverse effects. There is a great need for extensive and well planned research to find effective ways to manage this disease and to evaluate treatment strategies that might be curative. People with mycosis fungoides are encouraged to participate in such trials.

10.1002/14651858.CD008946.pub2

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Three eligible trials were identified. Two trials, including one trial with a much larger sample size than the others combined, were from geographical areas with low population selenium concentrations. Meta-analysis of the pooled data showed a significant reduction in the proportion of infants having one or more episodes of sepsis associated with selenium supplementation [summary RR 0.73 (0.57 to 0.93); RD -0.10 (-0.17 to -0.02); NNT 10 (5.9 to 50)]. Supplementation with selenium was not associated with improved survival, a reduction in neonatal chronic lung disease or retinopathy of prematurity. Supplementing very preterm infants with selenium is associated with benefit in terms of a reduction in one or more episodes of sepsis. Supplementation was not associated with improved survival, a reduction in neonatal chronic lung disease or retinopathy of prematurity. Supplemental doses of selenium for infants on parenteral nutrition higher than those currently recommended may be beneficial. The data are dominated by one large trial from a country with low selenium concentrations and may not be readily translated to other populations.

The review of trials of selenium supplementation for preterm babies found that it reduces sepsis (blood infection). It has not been shown to reduce other complications or increase survival. No adverse effects were reported. Higher than usual levels of selenium supplementation may be beneficial, but more research is needed as most of the evidence comes from a country where selenium levels were unusually low.

10.1002/14651858.CD003312

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We included eight trials randomising 232 preterm infants in this review. Inhalation corticosteroids did not reduce the separate or combined outcomes of death or BPD. The meta-analyses of the studies showed a reduced risk in favor of inhalation steroids regarding failure to extubate at seven days (typical RR (TRR) 0.80, 95% CI 0.66 to 0.98; 5 studies, 79 infants) and at the latest reported time point after treatment onset (TRR 0.60, 95% CI 0.45 to 0.80; 6 studies, 90 infants). However, both analyses showed increased statistical heterogeneity (I2 statistic 73% and 86%, respectively). Furthermore, inhalation steroids did not impact total duration of mechanical ventilation or oxygen dependency. There was a trend toward a reduction in the use of systemic corticosteroids in infants receiving inhalation corticosteroids (TRR 0.51, 95% CI 0.26 to 1.00; 4 studies, 74 infants; very low-quality evidence). There was a paucity of data on short- and long-term adverse effects. Our results should be interpreted with caution because the total number of randomised participants is relatively small, and most trials differed considerably in participant characteristics, inhalation therapy, and outcome definitions. Based on the results of the currently available evidence, inhalation corticosteroids initiated at ≥ 7 days of life for preterm infants at high risk of developing BPD cannot be recommended at this point in time. More and larger randomised, placebo-controlled trials are needed to establish the efficacy and safety of inhalation corticosteroids.

We identified eight studies investigating this therapy in 232 infants. Although we deemed the risk of bias as low, very few studies reported our outcomes of interest. The included trials did not show a beneficial effect of inhalation corticosteroids on death or BPD. In addition, the safety of inhalation corticosteroids was assessed in only a small number of trials. Based on these results, inhalation corticosteroids initiated after the first week of life cannot be recommended for preterm infants at risk of BPD. More studies are needed. The quality of the evidence was low to very low for the main outcomes.

10.1002/14651858.CD002311.pub4

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Fourteen trials met all inclusion criteria and were included in this review. In most of the studies, hawthorn was used as an adjunct to conventional treatment. Ten trials including 855 patients with chronic heart failure (New York Heart Association classes I to III) provided data that were suitable for meta-analysis. For the physiologic outcome of maximal workload, treatment with hawthorn extract was more beneficial than placebo (WMD (Watt) 5.35, 95% CI 0.71 to 10.00, P < 0.02, n = 380). Exercise tolerance were significantly increased by hawthorn extract (WMD (Watt x min) 122.76, 95% CI 32.74 to 212.78, n = 98). The pressure-heart rate product, an index of cardiac oxygen consumption, also showed a beneficial decrease with hawthorn treatment (WMD (mmHg/min) -19.22, 95% CI -30.46 to -7.98, n = 264). Symptoms such as shortness of breath and fatigue improved significantly with hawthorn treatment as compared with placebo (WMD -5.47, 95% CI -8.68 to -2.26, n = 239). No data on relevant mortality and morbidity such as cardiac events were reported, apart from one trial, which reported deaths (three in active, one in control) without providing further details. Reported adverse events were infrequent, mild, and transient; they included nausea, dizziness, and cardiac and gastrointestinal complaints. These results suggest that there is a significant benefit in symptom control and physiologic outcomes from hawthorn extract as an adjunctive treatment for chronic heart failure.

In this review, 14 double-blind, placebo controlled randomised clinical trials (RCTs) were found. They did not all measure the same outcomes and several did not explain what other heart failure treatments patients were receiving. Those trials that could be included in a meta-analysis showed improvements in heart failure symptoms and in the function of the heart. The results, therefore, are suggestive of a benefit from hawthorn extract used in addition to conventional treatments for chronic heart failure.

10.1002/14651858.CD005312.pub2

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Two randomised trials assessed the effectiveness of oral plus inhaled dual therapy versus oral monotherapy in a total of 118 adults with a mean age of 62.8 years. One multi-centre trial compared inhaled tobramycin plus oral ciprofloxacin versus ciprofloxacin alone, and one single-centre trial compared nebulised gentamicin plus systemic antibiotics versus a systemic antibiotic alone. Published papers did not report study funding sources. Effect estimates from one small study with 53 adults showed no evidence of treatment benefit with oral plus inhaled dual therapy for the following primary outcomes at the end of the study: successful management of exacerbation - cure at day 42 (odds ratio (OR) 0.66, 95% confidence interval (CI) 0.22 to 2.01; 53 participants; one study; very low-quality evidence); number of participants with Pseudomonas aeruginosa eradication at day 21 (OR 2.33, 95% CI 0.66 to 8.24; 53 participants; one study; very low-quality evidence); and serious adverse events (OR 0.48, 95% CI 0.08 to 2.87; 53 participants; one study; very low-quality evidence). Similarly, researchers provided no evidence of treatment benefit for the following secondary outcomes: clinical response rates - relapse at day 42 (OR 0.57, 95% CI 0.12 to 2.69; 53 participants; one study; very low-quality evidence); microbiological response rate at day 21 - eradicated (OR 2.40, 95% CI 0.67 to 8.65; 53 participants; one study; very low-quality evidence); and adverse events - incidence of wheeze (OR 5.75, 95% CI 1.55 to 21.33). Data show no evidence of benefit in terms of sputum volume, lung function, or antibiotic resistance. Outcomes from a second small study with 65 adults, available only as an abstract, were not included in the quantitative data synthesis. The included studies did not report our other primary outcomes: duration; frequency; and time to next exacerbation; nor our secondary outcomes: systemic markers of infection; exercise capacity; and quality of life. We did not identify any trials that included children. A small number of studies in adults have generated high-quality evidence that is insufficient to inform robust conclusions, and studies in children have provided no evidence. We identified only one dual-therapy combination of oral and inhaled antibiotics. Results from this single trial of 53 adults that we were able to include in the quantitative synthesis showed no evidence of treatment benefit with oral plus inhaled dual therapy in terms of successful treatment of exacerbations, serious adverse events, sputum volume, lung function, and antibiotic resistance. Further high-quality research is required to determine the efficacy and safety of other combinations of dual antibiotics for both adults and children with bronchiectasis, particularly in terms of antibiotic resistance.

In October 2017, we identified two relevant studies comparing oral plus inhaled dual therapy versus oral therapy alone. They included a total of 118 adults with an average age of 62.8 years. One study compared inhaled tobramycin plus oral ciprofloxacin with oral ciprofloxacin, and the second study compared inhaled gentamicin plus a systemic (affecting the whole body, rather than just the lungs) antibiotic with a systemic antibiotic alone. Only a research summary was available for the latter. Published papers did not report study funding sources Results from one small trial of 53 adults show no evidence of treatment benefit with oral plus inhaled dual therapy in terms of successful treatment of exacerbations, the occurrence of serious unwanted events, amount of phlegm, lung function, or resistance to antibiotic treatment. However, we found insufficient evidence to permit confident conclusions about their use. The overall quality of the evidence was very poor, largely because one of the studies was not well described and included few participants. Information on exacerbations, exercise ability, and quality of life was not reported. We did not identify any trials that compared other types of dual antibiotic therapy, and we found none that included children. Therefore uncertainty remains concerning the use of dual antibiotics, and further high-quality studies are needed to examine the role of dual antibiotics in the treatment of adults and children with bronchiectasis.

10.1002/14651858.CD012514.pub2

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For this update, we included seven additional studies, making a total of 21 included studies, which involved a total of 1400 participants: 635 received SET, 320 received HBET, and 445 received WA. In general, SET and HBET programs consisted of three exercise sessions per week. Follow-up ranged from six weeks to two years. Most trials used a treadmill walking test to investigate effects of exercise therapy on walking capacity. However, two trials assessed only quality of life, functional impairment, and/or walking behavior (i.e., daily steps measured by pedometer). The overall methodological quality of included trials was moderate to good. However, some trials were small with respect to numbers of participants, ranging from 20 to 304. SET groups showed clear improvement in MWD/T compared with HBET and WA groups, with overall SMDs at three months of 0.37 (95% confidence interval [CI] 0.12 to 0.62; P = 0.004; moderate-quality evidence) and 0.80 (95% CI 0.53 to 1.07; P < 0.00001; high-quality evidence), respectively. This translates to differences in increased MWD of approximately 120 and 210 meters in favor of SET groups. Data show improvements for up to six and 12 months, respectively. The HBET group did not show improvement in MWD/T compared with the WA group (SMD 0.30, 95% CI -0.45 to 1.05; P = 0.43; moderate-quality evidence). Compared with HBET, SET was more beneficial for PFWD/T but had no effect on quality of life parameters nor on self-reported functional impairment. Compared with WA, SET was more beneficial for PFWD/T and self-reported functional impairment, as well as for some quality of life parameters (e.g., physical functioning, pain, and physical component summary after 12 months), and HBET had no effect. Data show no obvious effects on mortality rates. Thirteen of the 1400 participants died, but no deaths were related to exercise therapy. Overall, adherence to SET was approximately 80%, which was similar to that reported with HBET. Only limited adherence data were available for WA groups. Evidence of moderate and high quality shows that SET provides an important benefit for treadmill-measured walking distance (MWD and PFWD) compared with HBET and WA, respectively. Although its clinical relevance has not been definitively demonstrated, this benefit translates to increased MWD of 120 and 210 meters after three months in SET groups. These increased walking distances are likely to have a positive impact on the lives of patients with IC. Data provide no clear evidence of a difference between HBET and WA. Trials show no clear differences in quality of life parameters nor in self-reported functional impairment between SET and HBET. However, evidence is of low and very low quality, respectively. Investigators detected some improvements in quality of life favoring SET over WA, but analyses were limited by small numbers of studies and participants. Future studies should focus on disease-specific quality of life and other functional outcomes, such as walking behavior and physical activity, as well as on long-term follow-up.

We included 21 trials in which a total of 1400 participants with intermittent claudication (65% male, mean age 66 years) had been assigned to supervised exercise therapy, home-based exercise therapy, or walking advice (search last run December 2016). The overall methodological quality of included trials was moderate to good. However, some trials had enrolled only small numbers of participants. Trials lasted from six weeks to two years. This review shows that patients participating in a supervised exercise program improve their walking ability to a greater extent than those completing a home-based exercise program or just following walking advice. After three months, the maximal walking distance for participants following the supervised exercise program was 120 or 210 meters farther than the maximal walking distance for those who followed a home-based exercise program or received walking advice, respectively. To put these increases in context, a US football field is roughly 90 meters (or 100 yards) long. Before participating in the exercise program, the maximal walking distance of participants was 290 meters with a pain-free walking distance of 140 meters, so this improvement is likely to have a positive impact on their lives. Results of the home-based exercise program were similar to those reported for walking advice. Compared with home-based exercise therapy, supervised exercise therapy was more beneficial for pain-free walking distance but had no effect on quality of life measures nor on self-reported functional impairment. Compared with walking advice, supervised exercise therapy was more beneficial for pain-free walking distance and self-reported functional impairment, as well as for some quality of life measures (e.g., physical functioning, pain, and physical component summary after 12 months), and home-based exercise therapy had no effect. Data show no obvious effects on mortality rates. Thirteen of the 1400 participants died, but no deaths were related to exercise therapy. Overall, adherence to supervised exercise therapy was approximately 80%, which was similar to that reported with home-based exercise therapy. Only limited adherence data were available for walking advice groups. Evidence of moderate and high quality shows that supervised exercise therapy improves walking distance (maximal and pain-free) to a greater extent than home-based exercise therapy and walking advice, respectively. Trials show no clear differences in quality of life measures nor in self-reported functional impairment between supervised exercise therapy and home-based exercise therapy. However, evidence is of low and very low quality, respectively. Investigators detected some improvements in quality of life favoring supervised exercise therapy over walking advice, but analyses were limited by small numbers of studies and participants. More research is needed on disease-specific quality of life and other functional outcomes, such as walking behavior and physical activity, as well as on long-term follow-up. Adhering to an exercise program is important because it leads to decreased leg pain and improved quality of life, as well as to likely improvement in general physical condition.

10.1002/14651858.CD005263.pub4

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We found five double-blind placebo-controlled trials that met our inclusion criteria. These trials assessed effectiveness and safety of drugs in a total of 50 people with intellectual disability demonstrating SIB. Four trials compared the effects of naltrexone versus placebo and one trial compared clomipramine versus placebo. One of the naltrexone versus placebo trials reported that naltrexone had clinically significant effects (≥ 33% reduction) on the daily rates of three of the four participants' most severe form of SIB and modest to substantial reductions in SIB for all participants; however, this study did not report on statistical significance. Another trial reported that naltrexone attenuated SIB in all four participants, with 25 mg and 50 mg doses producing a statistically significant decrease in SIB (P value < 0.05). Another trial (eight people) indicated that naltrexone administration was associated with significantly fewer days of high frequency self injury and significantly more days with low frequency self injury. Naltrexone had different effects depending on the form and location of self injury. Another trial with only 26 participants found that neither single-dose (100 mg) nor long-term (50 and 150 mg) naltrexone treatment had any therapeutic effect on SIB. Comparison of clomipramine versus placebo found no statistically significant benefit for any outcome measure, which included SIB rate and intensity, stereotypy and adverse events. However, it showed clinically significant improvement in the rate and intensity of SIB and stereotypy. There were very few noteworthy adverse events to report in any of the four trials in which these were reported. All trials were at high risk of bias, apart from one trial (Lewis 1996), which was probably at low risk of bias. The short period of follow-up was a significant drawback in the design of all five trials, as it did not allow long-term assessment of behaviour over time. We were unable to examine the efficacy of antidepressants other than clomipramine, antipsychotics, mood stabilisers or beta-blockers as we did not identify any relevant placebo-controlled trials. There was weak evidence in included trials that any active drug was more effective than placebo for people with intellectual disability demonstrating SIB. Due to sparse data, an absence of power and statistical significance, and high risk of bias for four of the included trials, we are unable to reach any definite conclusions about the relative benefits of naltrexone or clomipramine compared to placebo.

In this review we aimed to assess if medications used in the management of SIB in adults with intellectual disability are safe and help reduce the behaviours. We looked for studies that compared antidepressants, antipsychotics or mood stabilisers with no active medication (placebo). We found only five studies: four examined the effects of naltrexone, an opioid antagonist (which works through modulating pain perception) and one examined the antidepressant clomipramine. There were only a total of 50 participants included in these studies, which was not enough to determine whether or not the intervention resulted in any improvement. Three of the naltrexone studies and the one clomipramine study indicated the drugs resulted in clinical improvement in SIB, but more evidence is needed. The data is too limited for us to be able to draw any firm conclusions about the benefits or safety of any medications for SIB in this population. We need more studies where many more participants are involved to know whether medications help in reducing SIB and if they are safe.

10.1002/14651858.CD009084.pub2

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We selected 10 studies for inclusion in the review from 5236 studies identified in the search. These 10 studies included a total of 709 participants. Risk of bias for the included studies was assessed as high in six studies and as unclear in four studies. Two RCTs reported all-cause mortality. Among 413 participants, there was no clear evidence of a difference in mortality between CPAP and control groups, and considerable heterogeneity between trials was noted (risk ratio (RR) 1.28, 95% confidence interval (CI) 0.35 to 4.66; I2 = 75%). Six studies reported demonstrable atelectasis in the study population. A reduction in atelectasis was observed in the CPAP group, although heterogeneity between studies was substantial (RR 0.62, 95% CI 0.45 to 0.86; I2 = 61%). Pneumonia was reported in five studies, including 563 participants; CPAP reduced the rate of pneumonia, and no important heterogeneity was noted (RR 0.43, 95% CI 0.21 to 0.84; I2 = 0%). The number of participants identified as having serious hypoxia was reported in two studies, with no clear difference between CPAP and control groups, given imprecise results and substantial heterogeneity between trials (RR 0.48, 95% CI 0.22 to 1.02; I2 = 67%). A reduced rate of reintubation was reported in the CPAP group compared with the control group in two studies, and no important heterogeneity was identified (RR 0.14, 95% CI 0.03 to 0.58; I2 = 0%). Admission into the intensive care unit (ICU) for invasive ventilation and supportive care was reduced in the CPAP group, but this finding did not reach statistical significance (RR 0.45, 95% CI 0.18 to 1.14; I2 = 0). Secondary outcomes such as length of hospital stay and adverse effects were only minimally reported. A summary of findings table was constructed using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) principle. The quality of evidence was determined to be very low. Very low-quality evidence from this review suggests that CPAP initiated during the postoperative period might reduce postoperative atelectasis, pneumonia and reintubation, but its effects on mortality, hypoxia or invasive ventilation are uncertain. Evidence is not sufficiently strong to confirm the benefits or harms of CPAP during the postoperative period in those undergoing major abdominal surgery. Most of the included studies did not report on adverse effects attributed to CPAP. New, high-quality research is much needed to evaluate the use of CPAP in preventing mortality and morbidity following major abdominal surgery. With increasing availability of CPAP to our surgical patients and its potential to improve outcomes (possibly in conjunction with intraoperative lung protective ventilation strategies), unanswered questions regarding its efficacy and safety need to be addressed. Any future study must report on the adverse effects of CPAP.

We searched the literature until 15 September 2013. We included all adults who underwent elective major abdominal surgery. We included only studies in which the intervention was started postoperatively. We employed the standard methods of the Cochrane Anaesthesia Review Group for data collection and analysis. A total of 709 participants were included in the 10 selected trials. Considerable differences between studies were noted in the populations studied, duration of treatment and supportive care provided. Two controlled trials (413 participants) reported deaths; no clear evidence showed a difference between CPAP and control groups. Six trials (249 participants) reported on atelectasis, which was reduced in the CPAP group. Pneumonia was reported in five trials (563 participants), and the rate of pneumonia was reduced in the CPAP group. The need for further respiratory support with artificial ventilation (reintubation) was reported in two studies, which favoured CPAP. No clear evidence revealed a difference between CPAP and control groups in rates of admission to intensive care units, nor were severely low oxygen levels reported. Few studies reported on length of hospital stay and harm due to CPAP. Substantial variability was seen in trial characteristics (heterogeneity), and risk of bias was high in six of the 10 studies. The included studies were small, and some were at least 20 years old; currently, computed tomography (CT) scans are used more often than chest x-rays and clinical examination alone for diagnosis. The summary of findings (GRADE) suggests that the strength of evidence supporting the use of CPAP was ‘very low.’ This means that recommendations based on currently available evidence from randomized controlled trials investigating use of CPAP during the postoperative period are not definitive.

10.1002/14651858.CD008930.pub2

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This update located nine new studies, which were added to the six studies from our last update in 2008. This review now includes 15 studies (eight RCTs, five CBA and two ITS studies). All of these studies measured the effectiveness of IPE interventions compared to no educational intervention. Seven studies indicated that IPE produced positive outcomes in the following areas: diabetes care, emergency department culture and patient satisfaction; collaborative team behaviour and reduction of clinical error rates for emergency department teams; collaborative team behaviour in operating rooms; management of care delivered in cases of domestic violence; and mental health practitioner competencies related to the delivery of patient care. In addition, four of the studies reported mixed outcomes (positive and neutral) and four studies reported that the IPE interventions had no impact on either professional practice or patient care. This updated review reports on 15 studies that met the inclusion criteria (nine studies from this update and six studies from the 2008 update). Although these studies reported some positive outcomes, due to the small number of studies and the heterogeneity of interventions and outcome measures, it is not possible to draw generalisable inferences about the key elements of IPE and its effectiveness. To improve the quality of evidence relating to IPE and patient outcomes or healthcare process outcomes, the following three gaps will need to be filled: first, studies that assess the effectiveness of IPE interventions compared to separate, profession-specific interventions; second, RCT, CBA or ITS studies with qualitative strands examining processes relating to the IPE and practice changes; third, cost-benefit analyses.

Nine studies met the inclusion criteria for the review. These studies were added to the six that we found the last time we updated the review, bringing the total to 15 studies. Seven of these studies reported positive outcomes for healthcare processes or patient outcomes, or both, four studies reported mixed outcomes (positive and neutral) and four reported no effects of IPE. The studies differed in many respects. They were conducted in different areas of clinical practice and included different IPE interventions. The study designs and outcome measures were also different. All 15 studies compared outcomes following an IPE intervention to outcomes, either in similar clinical settings that did not receive the IPE intervention, or in the same clinical setting before the intervention was made. Because no studies compared an interprofessional intervention to a profession-specific intervention, our understanding of interprofessional interventions is limited. The small number of studies included in this review, and their varied nature, limit our understanding of the key components of IPE and its effectiveness. More studies are needed to allow sound conclusions to be reached about the effectiveness of IPE, as well as to inform IPE policy development. In particular, these should include: first, studies that assess the effectiveness of IPE interventions compared to separate, profession-specific interventions; second, RCT, CBA or ITS studies with qualitative strands examining processes relating to the IPE and practice changes; third, cost-benefit analyses.

10.1002/14651858.CD002213.pub3

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None of the studies of clinically-relevant hyperkalaemia reported mortality or cardiac arrhythmias. Reports focused on serum potassium levels. Many studies were small, and not all intervention groups had sufficient data for meta-analysis to be performed. On the basis of small studies, inhaled beta-agonists, nebulised beta-agonists, and intravenous (IV) insulin-and-glucose were all effective, and the combination of nebulised beta agonists with IV insulin-and-glucose was more effective than either alone. Dialysis is effective. Results were equivocal for IV bicarbonate. K-absorbing resin was not effective by four hours, and longer follow up data on this intervention were not available from RCTs. Nebulised or inhaled salbutamol, or IV insulin-and-glucose are the first-line therapies for the management of emergency hyperkalaemia that are best supported by the evidence. Their combination may be more effective than either alone, and should be considered when hyperkalaemia is severe. When arrhythmias are present, a wealth of anecdotal and animal data suggests that IV calcium is effective in treating arrhythmia. Further studies of the optimal use of combination treatments and of the adverse effects of treatments are needed.

No trials with clinically-important outcomes were identified. Many of the studies were conducted in convenience samples of patients. Many of the trials were methodologically flawed. Adverse events were rarely reported. Decrease in serum potassium was the most frequently reported outcome: for this outcome beta agonists and intravenous insulin-and-glucose were effective. The combination may be more effective than either alone.

10.1002/14651858.CD003235.pub2

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One study (34 patients) met our inclusion criteria although it was not yet a peer reviewed publication. The study randomised patients with chronic frontal sinusitis who had failed a prolonged course of medical treatment into two groups: balloon dilatation of the frontal recess (plus conventional FESS of other involved sinuses) versus conventional FESS (Draf type 1/2a procedures on the frontal sinuses). At 12 months follow up there was no statistically significant difference in radiological resolution of frontal sinuses between the two groups. The percentages of directly observed patent frontal recesses at 12 months were 75% in the balloon dilation group versus 63% in the FESS-only group. The authors state that this was statistically significant but details of the analysis were not presented. Indeed the study as a whole suffers from a bias in the way its outcome measures were reported. No major complications were reported. Three patients in the FESS-only group required further revision frontal sinus surgery compared to one in the balloon dilation group, although synechiae were more common in the latter. At present there is no convincing evidence supporting the use of endoscopic balloon sinus ostial dilation compared to conventional surgical modalities in the management of CRS refractory to medical treatment. With the escalating use of balloon sinuplasty, there is an urgent need for more randomised controlled trials to determine its efficacy over conventional surgical treatment modalities.

One unpublished trial met our inclusion criteria. This randomised 34 patients with chronic frontal sinusitis into two groups: in one group balloon dilation was used to open up the drainage pathways of the frontal sinuses; in the other group conventional endoscopic sinus surgery was used to do the same. For both groups all other sinuses were treated using conventional functional endoscopic sinus surgery. Balloon dilation did not show an improvement in the resolution of frontal sinusitis as demonstrated by imaging studies, however the technique was associated with an increased likelihood that someone observing a frontal sinus opening would find this open. However, it is not clear whether this was a statistically significant result. The study report appeared to be biased in the way it reported its outcome measures. At present, therefore, we cannot recommend the use of balloon dilation of sinus ostia over conventional surgical treatment modalities in this setting.

10.1002/14651858.CD008515.pub2

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Of seventeen included studies, thirteen found no evidence of an effect for continuous smoking abstinence following the intervention. Meta-analysis of 14 studies for point prevalence of smoking produced a statistically and clinically significant effect in favour of the intervention (OR 1.36, 95% CI 1.20 to 1.55, p= 0.004). Meta-analysis of eight studies that reported continuous abstinence was also statistically significant (OR 1.60, 95% CI 1.26 to 2.03, p= 0.03). Healthcare professionals who had received training were more likely to perform tasks of smoking cessation than untrained controls, including: asking patients to set a quit date (p< 0.0001), make follow-up appointments (p< 0.00001), counselling of smokers (p< 0.00001), provision of self-help material (p< 0.0001) and prescription of a quit date (p< 0.00001). No evidence of an effect was observed for the provision of nicotine gum/replacement therapy. Training health professionals to provide smoking cessation interventions had a measurable effect on the point prevalence of smoking, continuous abstinence and professional performance. The one exception was the provision of nicotine gum or replacement therapy, which did not differ between groups.

The review of 17 trials found that these training programs help health professionals to identify smokers and increase the number of people who quit smoking. The programs also increase the number of people offered advice and support for quitting by health professionals.

10.1002/14651858.CD000214.pub2

cochrane-simplification-train-2530

cochrane-simplification-train-2530

We included 22 studies involving 7436 participants comparing nine different types of securement device or dressing. All included studies were at unclear or high risk of performance bias due to the different appearances of the dressings and securement devices. The extent of blinding of outcome assessment was unclear in most studies. The quality of evidence varied between different comparisons and outcomes. We mainly downgraded the quality of evidence for imprecision, indirectness, risk of bias and inconsistency. It is unclear whether there is a difference in the rate of catheter-related BSI between securement with gauze and tape and standard polyurethane (SPU) (RR 0.64, 95% CI 0.26 to 1.63, low quality evidence), or between chlorhexidine gluconate-impregnated (CGI) dressings and SPU (RR 0.65, 95% CI 0.40 to 1.05, moderate quality evidence). There is high quality evidence that medication-impregnated dressings reduce the incidence of catheter-related BSI relative to all other dressing types (RR 0.60, 95% CI 0.39 to 0.93). There is moderate quality evidence that CGI dressings reduce the frequency of catheter-related BSI per 1000 patient days compared with SPU dressings (RR 0.51, 95% CI 0.33 to 0.78). There is moderate quality evidence that catheter tip colonisation is reduced with CGI dressings compared with SPU dressings (RR 0.58, 95% CI 0.47 to 0.73), but the relative effects of gauze and tape and SPU are unclear (RR 0.95, 95% CI 0.51 to 1.77, very low quality evidence). It is unclear if there is a difference in rates of skin irritation or damage when CGI dressings are compared with SPU dressings (moderate quality evidence) (RR 11.17, 95% CI 0.84 to 149.48). A multiple treatment meta-analysis found sutureless securement devices as likely to be the most effective at reducing the incidence of catheter-related BSI (low quality evidence), with CGI dressings ranked second (low quality evidence). Medication-impregnated dressing products reduce the incidence of catheter-related BSI relative to all other dressing types. There is some evidence that CGI dressings, relative to SPU dressings, reduce catheter-related BSI for the outcomes of frequency of infection per 1000 patient days, risk of catheter tip colonisation and possibly risk of catheter-related BSI. A multiple treatment meta-analysis found that sutureless securement devices are likely to be the most effective at reducing catheter-related BSI though this is low quality evidence. Most studies were conducted in intensive care unit (ICU) settings. More, high quality research is needed regarding the relative effects of dressing and securement products for CVCs. Future research may adjust the estimates of effect for the products included in this review and is needed to assess the effectiveness of new products.

The researchers searched medical databases up to September 2014, and identified 22 studies with a total of 7436 participants that were relevant to the research question. The studies investigated the following comparisons: - nine studies compared sterile gauze with standard polyurethane dressings; - six studies compared standard polyurethane dressings with chlorhexidine gluconate-impregnated dressings (chlorhexidine gluconate is an antibacterial disinfectant); - one study compared standard polyurethane dressings with silver-impregnated dressings (silver compounds may have antibacterial properties); - one study compared standard polyurethane dressings with hydrocolloid dressings; - one study compared 'modern' gas permeable standard polyurethane dressings with 'old' (original) standard polyurethane dressings; - one study compared highly adhesive transparent standard polyurethane dressings with chlorhexidine gluconate dressings; - one study compared standard polyurethane dressings with sutureless (stitchless) securement devices; - one study compared sterile gauze with no dressing; and - one study compared chlorhexidine gluconate dressings with no dressings. The included studies sometimes did not clearly report the methods they had used to minimise accidental or statistical error, but overall the methods were adequate. Analysis of the study results showed that there is high quality evidence that securing a CVC with a dressing impregnated with a medication (chlorhexidine gluconate-impregnated or silver) reduces catheter-related blood stream infection compared with a dressing without medication. The results indicated moderate quality evidence for a reduction in the frequency of catheter-related BSI per 1000 patient days (this is a unit used in research that represents patient use; in this case 1000 patient days is equal to 1000 patients using CVCs for one day, or 500 patients using CVCs for two days, or 250 patients using CVCs for four days, etc.) when a chlorhexidine gluconate-impregnated dressing was used rather than a standard polyurethane dressing. When the risk of infection with chlorhexidine gluconate-impregnated dressings was compared with the risk with standard polyurethane dressings in another way (by calculating the ratio of the risk of infection with one versus the other without taking account to patient days of use) this difference was less clear. A less direct measure of infection, that is the extent of bacterial colonisation of the tip of the catheter after removal, showed more bacteria with the standard polyurethane dressing (moderate quality evidence). The studies that contributed to this research were mainly carried out in intensive care unit settings, where a large number of CVCs are used for short durations. Other types of dressings and securement products for CVCs that were investigated by the studies analysed here did not show any observable effects on catheter-related BSI, catheter tip colonisation or any of the other outcomes assessed, such as skin irritation, failed catheter securement, condition of the dressing and patient death. More, high quality research is needed to investigate the relative effects of the wide range of dressing and securement products that are available for CVCs. This plain language summary is up-to-date as of 5th June, 2015.

10.1002/14651858.CD010367.pub2

cochrane-simplification-train-2531

cochrane-simplification-train-2531

Eight RCTs with a total of 8915 participants (4545 invasive strategies, 4370 conservative strategies) were eligible for inclusion. We included three new studies and 1099 additional participants in this review update. In the all-study analysis, evidence did not show appreciable risk reductions in all-cause mortality (RR 0.87, 95% CI 0.64 to 1.18; eight studies, 8915 participants; low quality evidence) and death or non-fatal MI (RR 0.93, 95% CI 0.71 to 1.2; seven studies, 7715 participants; low quality evidence) with invasive strategies compared to conservative (selective invasive) strategies at six to 12 months follow-up. There was appreciable risk reduction in MI (RR 0.79, 95% CI 0.63 to 1.00; eight studies, 8915 participants; moderate quality evidence), refractory angina (RR 0.64, 95% CI 0.52 to 0.79; five studies, 8287 participants; moderate quality evidence) and re-hospitalisation (RR 0.77, 95% CI 0.63 to 0.94; six studies, 6921 participants; moderate quality evidence) with routine invasive strategies compared to conservative (selective invasive) strategies also at six to 12 months follow-up. Evidence also showed increased risks in bleeding (RR 1.73, 95% CI 1.30 to 2.31; six studies, 7584 participants; moderate quality evidence) and procedure-related MI (RR 1.87, 95% CI 1.47 to 2.37; five studies, 6380 participants; moderate quality evidence) with routine invasive strategies compared to conservative (selective invasive) strategies. The low quality evidence were as a result of serious risk of bias and imprecision in the estimate of effect while moderate quality evidence was only due to serious risk of bias. In the all-study analysis, the evidence failed to show appreciable benefit with routine invasive strategies for unstable angina and non-ST elevation MI compared to conservative strategies in all-cause mortality and death or non-fatal MI at six to 12 months. There was evidence of risk reduction in MI, refractory angina and re-hospitalisation with routine invasive strategies compared to conservative (selective invasive) strategies at six to 12 months follow-up. However, routine invasive strategies were associated with a relatively high risk (almost double the risk) of procedure-related MI, and increased risk of bleeding complications. This systematic analysis of published RCTs supports the conclusion that, in patients with UA/NSTEMI, a selectively invasive (conservative) strategy based on clinical risk for recurrent events is the preferred management strategy.

We included randomised controlled trials that compared routine invasive strategies to conservative strategies in patients with UA and NSTEMI in the stent era. We searched the available literature up to 25 August 2015. We included eight studies with 8915 participants: five trials were in the review version published in 2010, and three were new trials. Of the included participants with UA and NSTEMI, there were 4545 in the invasive strategy arm and 4370 in the conservative strategy arm. Evidence failed to show appreciable risk reduction in all-cause mortality and death or non-fatal myocardial infarction (MI) with routine invasive management strategy compared to conservative strategies. There was appreciable risk reduction in MI, refractory angina and re-hospitalisation with routine invasive strategies compared to conservative strategies, but this was associated with an increased risk of procedure-related MI and bleeding complications. The quality of the evidence in this review update ranged from low quality to moderate quality. Low quality evidence was as a result of serious risk of bias and uncertainty surrounding the effect, while moderate quality evidence was only due to serious risk of bias. The debate continues as to which strategy is better. The invasive strategy reduces the incidence of further chest pain or re-hospitalisation. Also, long-term follow-up from three studies suggests that it lowers the risk of a heart attack over the next three to five years. However, the invasive strategy also is associated with double the risk of heart attack during or soon after initial treatment, as well as an increased risk of bleeding. In summary, the published scientific research suggests that the invasive strategy may have particular benefit in those patients who are at high risk for recurrent events, and that patients at low risk for a recurrent event may even suffer harm from such an approach.

10.1002/14651858.CD004815.pub4

cochrane-simplification-train-2532

cochrane-simplification-train-2532

We included five randomised controlled trials (RCTs) with 232 participants comparing haloperidol discontinuation with haloperidol continuation. Discontinuation was achieved in all five studies by replacing haloperidol with placebo. The trials' size ranged between 23 and 87 participants. The methods of randomisation, allocation concealment and blinding were poorly reported. Participants allocated to discontinuing haloperidol treatment were more likely to show no improvement in global state compared with those in the haloperidol continuation group (n = 49; 1 RCT; RR 2.06, 95% CI 1.33 to 3.20; very low quality evidence: our confidence in the effect estimate is limited due to relevant methodological shortcomings of included trials). Those who continued haloperidol treatment were less likely to experience a relapse compared to people who discontinued taking haloperidol (n = 165; 4 RCTs; RR 1.80, 95% CI 1.18 to 2.74; very low quality evidence). Satisfaction with treatment (measured as numbers leaving the study early) was similar between groups (n = 43; 1 RCT; RR 0.13, 95% CI 0.01 to 2.28; very low quality evidence). No usable mental state, general functioning, general behaviour or adverse effect data were reported by any of the trials. This review provides limited evidence derived from small, short-term studies. The longest study was for one year, making it difficult to generalise the results to a life-long disorder. Very low quality evidence shows that discontinuation of haloperidol is associated with an increased risk of relapse and a reduction in the risk of 'global state improvement'. However, participant satisfaction with haloperidol treatment was not different from participant satisfaction with haloperidol discontinuation as measured by leaving the studies early. Due to the very low quality of these results, firm conclusions cannot be made. In addition, the available studies did not report usable data regarding the adverse effects of haloperidol treatment. Considering that haloperidol is one of the most widely used antipsychotic drugs, it was surprising that only a small number of studies into the benefit and harm of haloperidol discontinuation were available. Moreover, the available studies did not report on outcomes that are important to clinicians and to people with schizophrenia, particularly adverse effects and social outcomes. Better designed trials are warranted.

We ran electronic searches of Cochrane Schizophrenia's trial register, most recently on 24 January 2019, for trials that randomised people with schizophrenia and are stable on haloperidol treatment to either discontinue taking haloperidol or to continue taking haloperidol. The review authors found and checked 54 records. Five trials met the review requirements and provided usable data. The evidence currently available from randomised controlled trials is of very low quality and suggests that haloperidol discontinuation is associated with poorer outcomes for people with schizophrenia in terms of their overall symptom improvement (global state). It also shows that people discontinuing haloperidol treatment are more likely to experience relapse (reoccurrence of symptoms) during the first year post treatment. There were no trials providing evidence on what happens after the first year. The number of participants leaving the study early (which can be an indication of satisfaction with treatment) was similar between the two treatments. The very low quality of the currently available evidence is due to methodological shortcomings of the included trials. This lowers our confidence in the reliability of results, and hampers their generalisability to real-world situations. It is disappointing that only a small number of studies were identified, and the size and quality of these studies were limited. The evidence available does not enable us to fully answer important questions regarding the effects of discontinuing haloperidol treatment. In particular there is no evidence available related to the side effects of haloperidol. New trials of better quality are needed.

10.1002/14651858.CD011408.pub2

cochrane-simplification-train-2533

cochrane-simplification-train-2533

We included 69 trials with 4860 participants: 2404 given epidural analgesia and 2456 receiving comparators (systemic analgesia, peripheral nerve block, intrapleural analgesia, or wound infiltration). The mean (or median) age of participants varied between 43.5 years and 74.6 years. Surgeries performed were coronary artery bypass grafting or valvular procedures and surgeries for congenital heart disease. We judged that no trials were at low risk of bias for all domains, and that all trials were at unclear/high risk of bias for blinding of participants and personnel taking care of study participants. Epidural analgesia versus systemic analgesia Trials show there may be no difference in mortality at 0 to 30 days (risk difference (RD) 0.00, 95% confidence interval (CI) −0.01 to 0.01; 38 trials with 3418 participants; low-quality evidence), and there may be a reduction in myocardial infarction at 0 to 30 days (RD −0.01, 95% CI −0.02 to 0.00; 26 trials with 2713 participants; low-quality evidence). Epidural analgesia may reduce the risk of 0 to 30 days respiratory depression (RD −0.03, 95% CI −0.05 to −0.01; 21 trials with 1736 participants; low-quality evidence). There is probably little or no difference in risk of pneumonia at 0 to 30 days (RD −0.03, 95% CI −0.07 to 0.01; 10 trials with 1107 participants; moderate-quality evidence), and epidural analgesia probably reduces the risk of atrial fibrillation or atrial flutter at 0 to 2 weeks (RD −0.06, 95% CI −0.10 to −0.01; 18 trials with 2431 participants; moderate-quality evidence). There may be no difference in cerebrovascular accidents at 0 to 30 days (RD −0.00, 95% CI −0.01 to 0.01; 18 trials with 2232 participants; very low-quality evidence), and none of the included trials reported any epidural haematoma events at 0 to 30 days (53 trials with 3982 participants; low-quality evidence). Epidural analgesia probably reduces the duration of tracheal intubation by the equivalent of 2.4 hours (standardized mean difference (SMD) −0.78, 95% CI −1.01 to −0.55; 40 trials with 3353 participants; moderate-quality evidence). Epidural analgesia reduces pain at rest and on movement up to 72 hours after surgery. At six to eight hours, researchers noted a reduction in pain, equivalent to a reduction of 1 point on a 0 to 10 pain scale (SMD −1.35, 95% CI −1.98 to −0.72; 10 trials with 502 participants; moderate-quality evidence). Epidural analgesia may increase risk of hypotension (RD 0.21, 95% CI 0.09 to 0.33; 17 trials with 870 participants; low-quality evidence) but may make little or no difference in the need for infusion of inotropics or vasopressors (RD 0.00, 95% CI −0.06 to 0.07; 23 trials with 1821 participants; low-quality evidence). Epidural analgesia versus other comparators Fewer studies compared epidural analgesia versus peripheral nerve blocks (four studies), intrapleural analgesia (one study), and wound infiltration (one study). Investigators provided no data for pulmonary complications, atrial fibrillation or flutter, or for any of the comparisons. When reported, other outcomes for these comparisons (mortality, myocardial infarction, neurological complications, duration of tracheal intubation, pain, and haemodynamic support) were uncertain due to the small numbers of trials and participants. Compared with systemic analgesia, epidural analgesia may reduce the risk of myocardial infarction, respiratory depression, and atrial fibrillation/atrial flutter, as well as the duration of tracheal intubation and pain, in adults undergoing cardiac surgery. There may be little or no difference in mortality, pneumonia, and epidural haematoma, and effects on cerebrovascular accident are uncertain. Evidence is insufficient to show the effects of epidural analgesia compared with peripheral nerve blocks, intrapleural analgesia, or wound infiltration.

We included randomized controlled trials involving adults undergoing any type of cardiac surgery under general anaesthesia with or without cardiopulmonary bypass where researchers compared epidural pain relief around the time of surgery against other forms of pain relief. Surgeries performed were coronary artery bypass grafting or valvular procedures and surgeries for congenital heart disease. The average age of participants was between 43 and 75 years. Outcomes were measured up to one year after surgery. We included 69 studies with 4860 participants. Where stated, the studies were funded by governmental resources (five studies), charity (eight), institutional resources (23), or in part by the industry (two). In all, 31 trials did not mention the source of funding. The evidence is current to November 2018. When researchers compared epidural analgesia versus systemic pain relief (e.g. by an analgesic given directly into a vein), they could not detect any difference in the number of deaths in the first 30 days after surgery (38 studies, 3418 participants). There might be a difference in the number of people experiencing heart attacks (26 studies, 2713 participants). These findings were supported by low-quality evidence. We found a small reduction in the risk of respiratory depression with epidural pain relief (21 studies, 1736 participants), but not in the risk of pneumonia (10 studies, 1107 participants) (low- or moderate-quality evidence). The reduced risk of respiratory depression was more obvious when cardiopulmonary bypass was needed for cardiac surgery. Epidural analgesia reduced the risk of atrial fibrillation or atrial flutter early in recovery at zero to two weeks (18 studies, 2431 participants; moderate-quality evidence). The number of cerebrovascular accidents was not clearly different (18 studies, 2232 participants), and no lasting neurological complications or epidural haematomas were reported (53 studies, 3982 participants; very low- or low-quality evidence). Although epidural analgesia may have reduced the duration of tracheal intubation, this was noted mainly in older studies, and clinical practices have changed since that time (40 trials, 3353 participants; moderate-quality evidence). We found only six studies that compared epidural pain relief versus application of local anaesthetic on the body surface to produce peripheral nerve blocks directly into the space around the lungs (intrapleural analgesia) and onto the surgical wound (wound infiltration). These studies provided low- or very low-quality evidence and did not report on many of the outcomes for this review. Study authors reported no heart attacks and no epidural haematomas. We rated the quality of evidence as moderate, low, or very low. We included too few participants in our review to rule out any differences in the number of patient deaths between epidural analgesia and systemic analgesia, nor to see any increase in epidural haematomas.

10.1002/14651858.CD006715.pub3

cochrane-simplification-train-2534

cochrane-simplification-train-2534

Eight studies are included in this review; six employed a crossover design. In the overall comparison of radiant warmers vs incubators, radiant warmers caused a statistically significant increase in insensible water loss (IWL) [WMD 0.94g/Kg/day (95% CI 0.47, 1.41)] and a trend towards increased oxygen consumption which was not statistically significant [WMD 0.27mL/kg/min (95% CI -0.09, 0.63)]. Due to small numbers, effects on important clinical outcomes could not be adequately assessed. A comparison of radiant warmers with heat shields vs incubators without heat shields showed a trend for increased IWL in the radiant warmer group, which was not statistically significant. No difference was shown in oxygen consumption. Radiant warmers result in increased IWL compared to incubators. This needs to be taken into account when calculating daily fluid requirements. The results of this review do not provide sufficient evidence concerning effects on important outcomes to guide clinical practice. Further randomised controlled trials are required to assess the effects of radiant warmers versus incubators in neonatal care on important short and long term outcomes, with particular attention to extremely low birthweight infants in the early neonatal period.

The review of trials found that radiant warmers increase water loss in low birthweight babies in the newborn period when compared to incubators and that this water loss needs to be taken into account when daily fluid requirements are calculated. However, there was not enough information available for this review to enable assessment of other important effects of radiant warmers. Therefore, at the present time, it is not clear which method of maintaining body temperature is best for newborn babies - radiant warmers or incubators. More research is necessary.

10.1002/14651858.CD000435

cochrane-simplification-train-2535

cochrane-simplification-train-2535

Thirty-nine studies which reported quantitative or qualitative data, or both, were included in the review. Thirty-three quantitative studies were identified. This included five randomised controlled trials (RCTs) and 10 non-experimental studies of warmth improvements, 12 non-experimental studies of rehousing or retrofitting, three non-experimental studies of provision of basic improvements in low or mIddle Income countries (LMIC), and three non-experimental historical studies of rehousing from slums. Fourteen quantitative studies (42.4%) were assessed to be poor quality and were not included in the synthesis. Twelve studies reporting qualitative data were identified. These were studies of warmth improvements (n = 7) and rehousing (n = 5). Three qualitative studies were excluded from the synthesis due to lack of clarity of methods. Six of the included qualitative studies also reported quantitative data which was included in the review. Very little quantitative synthesis was possible as the data were not amenable to meta-analysis. This was largely due to extreme heterogeneity both methodologically as well as because of variations in the intervention, samples, context, and outcome; these variations remained even following grouping of interventions and outcomes. In addition, few studies reported data that were amenable to calculation of standardized effect sizes. The data were synthesised narratively. Data from studies of warmth and energy efficiency interventions suggested that improvements in general health, respiratory health, and mental health are possible. Studies which targeted those with inadequate warmth and existing chronic respiratory disease were most likely to report health improvement. Impacts following housing-led neighbourhood renewal were less clear; these interventions targeted areas rather than individual households in most need. Two poorer quality LMIC studies reported unclear or small health improvements. One better quality study of rehousing from slums (pre-1960) reported some improvement in mental health. There were few reports of adverse health impacts following housing improvement. A small number of studies gathered data on social and socio-economic impacts associated with housing improvement. Warmth improvements were associated with increased usable space, increased privacy, and improved social relationships; absences from work or school due to illness were also reduced. Very few studies reported differential impacts relevant to equity issues, and what data were reported were not amenable to synthesis. Housing investment which improves thermal comfort in the home can lead to health improvements, especially where the improvements are targeted at those with inadequate warmth and those with chronic respiratory disease. The health impacts of programmes which deliver improvements across areas and do not target according to levels of individual need were less clear, but reported impacts at an area level may conceal health improvements for those with the greatest potential to benefit. Best available evidence indicates that housing which is an appropriate size for the householders and is affordable to heat is linked to improved health and may promote improved social relationships within and beyond the household. In addition, there is some suggestion that provision of adequate, affordable warmth may reduce absences from school or work. While many of the interventions were targeted at low income groups, a near absence of reporting differential impacts prevented analysis of the potential for housing improvement to impact on social and economic inequalities.

Poor housing is associated with poor health. This suggests that improving housing conditions might lead to improved health for residents. This review searched widely for studies from anywhere in the world which had investigated whether or not investment to improve housing conditions is linked with improvement in health. A huge amount of research on housing and health has been published but very few studies have investigated if improved housing conditions impact on residents' health. Neighbourhood renewal programmes often include housing improvements but a key aim of these programmes is to improve the area by attracting new residents, often those who are better off. In these programmes, improvements in health statistics may simply reflect a change in the population living in an area and the original population may not have benefited from the improved living conditions. This review only looked at studies where changes in health for the original population were being investigated rather than changes for the area. We identified 39 studies which assessed changes in health following housing improvement. The studies covered a wide range of housing improvements. The housing improvements in high income countries, and conducted in the past 30 years, included refurbishment, rehousing, relocation, installation of central heating and insulation. Studies from the developing world included provision of latrines. Older studies (pre-1965) examined changes in health following rehousing from slums. Overall, it would appear that improvements to housing conditions can lead to improvements in health. Improved health is most likely when the housing improvements are targeted at those with poor health and inadequate housing conditions, in particular inadequate warmth. Area based housing improvement programmes, for example programmes of housing-led neighbourhood renewal, which improve housing regardless of individual need may not lead to clear improvements in housing conditions for all the houses in a neighbourhood. This may explain why health improvements following these programmes are not always obvious. Improvements in warmth and affordable warmth may be an important reason for improved health. Improved health may also lead to reduced absences from school or work. Improvements in energy efficiency and provision of affordable warmth may allow householders to heat more rooms in the house and increase the amount of usable space in the home. Greater usable living space may lead to more use of the home, allow increased levels of privacy, and help with relationships within the home. An overview of the best available research evidence suggests that housing which promotes good health needs to be an appropriate size to meet household needs, and be affordable to maintain a comfortable indoor temperature.

10.1002/14651858.CD008657.pub2

cochrane-simplification-train-2536

cochrane-simplification-train-2536

We included 36 RCTs (2706 participants), of which 31 examined topical steroids; seven, calcineurin inhibitors; and three, lithium salts. The comparative interventions included placebo, azoles, calcipotriol, a non-steroidal anti-inflammatory compound, and zinc, as well as different anti-inflammatory treatments compared against each other. Our outcomes of interest were total clearance of symptoms, erythema, scaling or pruritus scores, and adverse effects. The risk of bias in studies was most frequently classified as unclear, due to unclear reporting of methods. Steroid treatment resulted in total clearance more often than placebo in short-term trials (four weeks or less) (relative risk (RR) 3.76, 95% confidence interval (CI) 1.22 to 11.56, three RCTs, 313 participants) and in one long-term trial (lasting 12 weeks). Steroids were also more effective in reducing erythema, scaling, and pruritus. Adverse effects were similar in both groups. There may be no difference between steroids and calcineurin inhibitors in total clearance in the short-term (RR 1.08, 95% 0.88 to 1.32, two RCTs, 60 participants, low-quality evidence). Steroids and calcineurin inhibitors were found comparable in all other assessed efficacy outcomes as well (five RCTs, 237 participants). Adverse events were less common in the steroid group compared with the calcineurin group in the short-term (RR 0.22, 95% CI 0.05 to 0.89, two RCTs, 60 participants). There were comparable rates of total clearance in the steroid and azole groups (RR 1.11, 95% CI 0.94 to 1.32, eight RCTs, 464 participants, moderate-quality evidence) as well as of adverse effects in the short-term, but less erythema or scaling with steroids. We found mild (class I and II) and strong (class III and IV) steroids comparable in the assessed outcomes, including adverse events. The only exception was total clearance in long-term use, which occurred more often with a mild steroid (RR 0.79, 95% CI 0.63 to 0.98, one RCT, 117 participants, low-quality evidence). In one study, calcineurin inhibitor was more effective than placebo in reducing erythema and scaling, but there were similar rates in total clearance or adverse events for short-term treatment. In another study, calcineurin inhibitor was comparable with azole when erythema, scaling, or adverse effects were measured for longer-term treatment. Lithium was more effective than placebo with regard to total clearance (RR 8.59, 95% CI 2.08 to 35.52, one RCT, 129 participants) with a comparable safety profile. Compared with azole, lithium resulted in total clearance more often (RR 1.79, 95% CI 1.10 to 2.90 in short-term treatment, one RCT, 288 participants, low-quality evidence). Topical steroids are an effective treatment for seborrhoeic dermatitis of the face and scalp in adolescents and adults, with no differences between mild and strong steroids in the short-term. There is some evidence of the benefit of topical calcineurin inhibitor or lithium salt treatment. Treatment with azoles seems as effective as steroids concerning short-term total clearance, but in other outcomes, strong steroids were more effective. Calcineurin inhibitor and azole treatment appeared comparable. Lithium salts were more effective than azoles in producing total clearance. Steroids are similarly effective to calcineurin inhibitors but with less adverse effects. Most of the included studies were small and short, lasting four weeks or less. Future trials should be appropriately blinded; include more than 200 to 300 participants; and compare steroids to calcineurin inhibitors or lithium salts, and calcineurin inhibitors to azoles or lithium salts. The follow-up time should be at least one year, and quality of life should be addressed. There is also a need for the development of well-validated outcome measures.

We included 36 randomised controlled trials with 2706 participants, examining the effect of anti-inflammatory treatments on seborrhoeic dermatitis. These trials were short-term; most of them lasting four weeks or less. Topical steroid treatment (such as hydrocortisone and betamethasone), topical calcineurin inhibitor treatment (such as tacrolimus and pimecrolimus), and topical lithium salts all reduced the symptoms of seborrhoeic dermatitis when compared with placebo treatment. Mild (such as hydrocortisone 1%) and strong (such as betamethasone) steroid compounds were comparable in short-term follow up. Short-term total clearance was achieved with antifungal azole treatment (such as ketoconazole and miconazole), as well as with steroids. Strong steroids were better than azole treatment in reducing erythema, scaling, and pruritus, and were comparable in terms of safety. Steroids were also as effective as calcineurin inhibitors, but side-effects occurred more often with calcineurin inhibitors. We found no differences between calcineurin inhibitors and azole treatments in effectiveness or side-effects. Lithium was more effective than azoles but had a similar frequency of side-effects (one study). The most common side-effects were burning, itching, erythema, and dryness in all treatment groups. Topical anti-inflammatory agents are useful in treating seborrhoeic dermatitis. Steroids are the most investigated anti-inflammatories. We still do not know the effects and safety of topical anti-inflammatory treatments in long-term or continuous use. This is regrettable as the disease is chronic in nature. Furthermore, there are no data concerning the effects of different treatments on quality of life.

10.1002/14651858.CD009446.pub2

cochrane-simplification-train-2537

cochrane-simplification-train-2537

We included 16 studies (eight individually randomised trials, four cluster randomised trials, three non-randomised trials, and one controlled before-after study). Twelve studies were conducted in the USA, while there was one study each from: Australia, Sweden, Tanzania, and the UK. Ten studies had unclear or high risk of bias. We categorised interventions as recipient-oriented, provider-oriented, or health systems-oriented. The interventions targeted adolescent boys or girls or both (seven studies), parents (four studies), and providers (two studies). Five studies had mixed participants that included adolescents and parents, adolescents and healthcare providers, and parents and healthcare providers. The outcomes included uptake of human papillomavirus (HPV) (11 studies); hepatitis B (three studies); and tetanus–diphtheria–acellular–pertussis (Tdap), meningococcal, HPV, and influenza (three studies) vaccines among adolescents. Health education improves HPV vaccine uptake compared to usual practice (RR 1.43, 95% CI 1.16 to 1.76; I² = 0%; 3 studies, 1054 participants; high-certainty evidence). In addition, one large study provided evidence that a complex multi-component health education intervention probably results in little to no difference in hepatitis B vaccine uptake compared to simplified information leaflets on the vaccine (RR 0.98, 95% CI 0.97 to 0.99; 17,411 participants; moderate-certainty evidence). Financial incentives may improve HPV vaccine uptake compared to usual practice (RR 1.45, 95% CI 1.05 to 1.99; 1 study, 500 participants; low-certainty evidence). However, we are uncertain whether combining health education and financial incentives has an effect on hepatitis B vaccine uptake, compared to usual practice (RR 1.38, 95% CI 0.96 to 2.00; 1 study, 104 participants; very low certainty evidence). Mandatory vaccination probably leads to a large increase in hepatitis B vaccine uptake compared to usual practice (RR 3.92, 95% CI 3.65 to 4.20; 1 study, 6462 participants; moderate-certainty evidence). Provider prompts probably make little or no difference compared to usual practice, on completion of Tdap (OR 1.28, 95% CI 0.59 to 2.80; 2 studies, 3296 participants), meningococcal (OR 1.09, 95% CI 0.67 to 1.79; 2 studies, 3219 participants), HPV (OR 0.99, 95% CI 0.55 to 1.81; 2 studies, 859 participants), and influenza (OR 0.91, 95% CI 0.61 to 1.34; 2 studies, 1439 participants) vaccination schedules (moderate-certainty evidence). Provider education with performance feedback may increase the proportion of adolescents who are offered and accept HPV vaccination by clinicians, compared to usual practice. Compared to adolescents visiting non-participating clinicians (in the usual practice group), the adolescents visiting clinicians in the intervention group were more likely to receive the first dose of HPV during preventive visits (5.7 percentage points increase) and during acute visits (0.7 percentage points for the first and 5.6 percentage points for the second doses of HPV) (227 clinicians and more than 200,000 children; low-certainty evidence). A class-based school vaccination strategy probably leads to slightly higher HPV vaccine uptake than an age-based school vaccination strategy (RR 1.09, 95% CI 1.06 to 1.13; 1 study, 5537 participants; moderate-certainty evidence). A multi-component provider intervention (including an education session, repeated contacts, individualised feedback, and incentives) probably improves uptake of HPV vaccine compared to usual practice (moderate-certainty evidence). A multi-component intervention targeting providers and parents involving social marketing and health education may improve HPV vaccine uptake compared to usual practice (RR 1.41, 95% CI 1.25 to 1.59; 1 study, 25,869 participants; low-certainty evidence). Various strategies have been evaluated to improve adolescent vaccination including health education, financial incentives, mandatory vaccination, and class-based school vaccine delivery. However, most of the evidence is of low to moderate certainty. This implies that while this research provides some indication of the likely effect of these interventions, the likelihood that the effects will be substantially different is high. Therefore, additional research is needed to further enhance adolescent immunisation strategies, especially in low- and middle-income countries where there are limited adolescent vaccination programmes. In addition, it is critical to understand the factors that influence hesitancy, acceptance, and demand for adolescent vaccination in different settings. This is the topic of an ongoing Cochrane qualitative evidence synthesis, which may help to explain why and how some interventions were more effective than others in increasing adolescent HPV vaccination coverage.

The review authors found 16 relevant studies. Twelve of the studies were from the USA. The other studies were one each from Australia, Sweden, Tanzania, and the UK. These studies showed the following. When adolescents (girl or boys, or both) and their parents were given vaccination information and education, more adolescents got HPV vaccines (high-certainty evidence). When adolescents were given gift vouchers, more adolescents may have got HPV vaccines (low-quality evidence). However, we were uncertain whether giving adolescents and their parents health education, cash, and gift packages led to more adolescents getting hepatitis B vaccines (very low certainty evidence). When laws were passed stating that adolescents must be vaccinated to go to school, substantially more adolescents probably got hepatitis B vaccines (moderate-certainty evidence). When healthcare providers were reminded to vaccinate adolescents when they opened their electronic medical charts, this probably had little or no effect on the number of adolescents who got tetanus–diphtheria–pertussis, meningococcal, HPV, or influenza vaccines (moderate-certainty evidence). When healthcare providers were given education with performance feedback, more adolescents may have got HPV vaccines (low-certainty evidence). When healthcare providers were given education, individualised feedback, frequent visits, and incentives, more adolescents probably got HPV vaccines (moderate-certainty evidence). When healthcare providers and parents were targeted in several ways, including through education, telephone calls, and radio messages, more adolescents may have got HPV vaccines (low-certainty evidence). These studies compared the use of these approaches (health education, gifts and rewards, laws, or reminders) to using no approaches. In addition, one study from Tanzania gave vaccination information to all girls that were in school class six but were not necessarily of the same age. They were compared to girls who were given vaccination information because they were all born in the same year, but were not necessarily in the same class. This study showed that the class-based approach probably led to slightly more girls getting HPV vaccines (moderate-certainty evidence). How up-to-date is this review? The review authors searched for studies that had been published up to 31 October 2018.

10.1002/14651858.CD011895.pub2

cochrane-simplification-train-2538

cochrane-simplification-train-2538

Overall, there were 75 trials (13,793 women); these were of mixed quality. In nine trials comparing oral misoprostol with placebo (1109 women), women using oral misoprostol were more likely to give birth vaginally within 24 hours (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.05 to 0.49; one trial; 96 women) and less likely to undergo caesarean birth (RR 0.72, 95% CI 0.54 to 0.95; 8 trials; 1029 women). Differences in ‘uterine hyperstimulation with fetal heart rate changes’ were compatible with no effect (RR 2.71, 95% CI 0.84 to 8.68; 7 trials; 669 women). Ten trials compared oral misoprostol with vaginal prostaglandin (dinoprostone) (3,240 women). There was little difference in the frequency of: vaginal birth within 24 hours (RR 1.10, 95% CI 0.99 to 1.22; 5 trials; 2,128 women), uterine hyperstimulation with fetal heart rate changes (RR 0.95, 95% CI 0.59 to 1.53; 7 trials; 2,352 women), and caesarean birth (RR 0.92, 95% CI 0.81 to 1.04; 10 trials; 3240 women). Five trials compared administration of oral misoprostol with intracervical prostaglandin E2 (681 women). Oral misoprostol was associated with fewer instances of failure to achieve vaginal birth within 24 hours (RR 0.78, 95% CI 0.63 to 0.97; 3 trials; 452 women) but more frequent uterine hyperstimulation with fetal heart rate changes (RR 3.57, 95% CI 1.11 to 11.54; 3 trials; 490 women). The available data for this comparison were however limited and the differences in caesarean birth were small (RR 0.85, 95% CI 0.63 to 1.16; 5 trials; 742 women). Nine trials compared oral misoprostol with intravenous oxytocin (1282 women). There were no obvious differences in the frequency of: vaginal birth within 24 hours (RR 0.79, 95% CI 0.59 to 1.05; 6 trials; 789 women), or uterine hyperstimulation with fetal heart rate changes (RR 1.30, 95% CI 0.43 to 3.91; 7 trials; 947 women). There were, however, fewer caesarean births with oral misoprostol (RR 0.77, 95% CI 0.60 to 0.98; 9 trials; 1282 women). Thirty-seven trials compared oral misoprostol with vaginal misoprostol (6417 women). There was little difference in the frequency of: vaginal birth within 24 hours (RR 1.08, 95% CI 0.86 to 1.36; 14 trials; 2,448 women), uterine hyperstimulation with fetal heart rate changes (RR 0.71, 95% CI 0.47 to 1.08; 29 trials; 5,503 women), and caesarean birth (RR 0.93, 95% CI 0.81 to 1.07; 35 trials; 6,326 women). The incidence of serious neonatal or maternal morbidity or death was rare and no meaningful results were available for any of the comparisons. Oral misoprostol as an induction agent is effective at achieving vaginal birth. It is more effective than placebo, as effective as vaginal misoprostol and vaginal dinoprostone, and results in fewer caesarean sections than oxytocin alone. Where misoprostol remains unlicensed for the induction of labour, many practitioners will prefer to use a licensed product like dinoprostone. If using oral misoprostol, the evidence suggests that the dose should be 20 to 25 mcg in solution. Given that safety is the primary concern, the evidence supports the use of oral regimens over vaginal regimens. This is especially important in situations where the risk of ascending infection is high and the lack of staff means that women cannot be intensely monitored.

The search for trials took place in January 2014. This review of 75 randomised controlled trials (13,793 women) found that oral misoprostol appears to be at least as effective as current methods of induction. Nine trials (1,282 women) showed that oral misoprostol was equivalent to intravenous infusion of oxytocin. There were no obvious differences in the number of women who had a vaginal birth within 24 hours, or the number of women who experienced uterine hyperstimulation with changes to the baby's heart rate, although there were fewer caesarean sections in the group of women who were given oral misoprostol. For the 37 thirty seven trials (6,417 women) that compared oral and vaginal misoprostol, there was little difference in the number of women who had a vaginal birth within 24 hours, uterine hyperstimulation with changes to the baby's heart rate, or caesarean section. In 10 trials (3,240 women) comparing oral misoprostol with a vaginal prostaglandin (dinoprost), there was little difference in the frequency of vaginal birth within 24 hours, uterine hyperstimulation with changes to the baby's heart rate, or caesarean section. The nine trials that compared oral misoprostol with placebo (1,109 women) and found that oral misoprostol is more effective than placebo for inducing labour. Women in the oral misoprostol group were more likely to have vaginal birth within 24 hours, and less likely to have a caesarean section. There was little difference between groups in terms of the number of women who experienced uterine hyperstimulation with changes to the baby's heart rate. Five trials compared oral misoprostol with intracervical (inserted into the entrance of the womb) prostaglandin E2 (681 women). Oral misoprostol was associated with fewer instances of failure to achieve vaginal birth within 24 hours but more frequent uterine hyperstimulation with changes to the baby's heart rate. The available data for this comparison was limited and the differences in caesarean birth were small. Overall, the incidence of serious illness or death of the mother or her baby was rare and no meaningful results were available for any of the comparisons in this review. Using oral misoprostol to induce labour is effective at achieving vaginal birth. It is more effective than placebo, as effective as vaginal misoprostol and vaginal dinoprostone, and results in fewer caesarean sections than using oxytocin alone. In some countries where misoprostol is not licenced for the purpose of inducing labour, many clinicians may prefer to use some other licensed product such as dinoprostone. Where oral misoprostol is used, evidence suggests that an appropriate dose may be 20 to 25 mcg in solution. Given that safety is the primary concern, the evidence supports the use of oral regimens over vaginal regimens. This is particularly important in settings where the mother is at a higher risk of infection and where there may be insufficient staff to closely monitor the mother and her baby.

10.1002/14651858.CD001338.pub3

cochrane-simplification-train-2539

cochrane-simplification-train-2539

Fourteen studies (n = 1245) met the inclusion criteria. Eleven studies compared CBT with control and comparisons at 0 to 3 months post-treatment showed beneficial effects of therapy that ranged from medium (when defined by financial loss from gambling: SMD -0.52; 95% confidence interval (CI) -0.71 to -0.33, n = 505) to very large (for gambling symptom severity: SMD -1.82; 95% CI -2.61 to -1.02, n = 402). Only one study (n = 147) compared groups at 9 to 12 months follow-up and produced smaller effects that were not significant. Four studies of motivational interviewing therapy were identified and mainly considered samples demonstrating less severe gambling (relative to studies of pathological gamblers). Data suggested reduced financial loss from gambling following motivational interviewing therapy at 0 to 3 months post-treatment (SMD -0.41; 95% CI -0.75 to -0.07, n = 244), although comparisons on other outcomes were not significant. The effect approached zero when defined by gambling symptom severity (SMD -0.03; 95% CI -0.55 to 0.50, n = 163). Studies compared groups at 9 to 12 months follow-up and found a significant effect of motivational interviewing therapy in terms of frequency of gambling (SMD -0.53; 95% CI -1.04 to -0.02, n = 62), with comparisons on other outcomes that were not significant. Two studies of integrative therapies also considered samples demonstrating overall low gambling severity, and found no significant effects of therapy at 0 to 3 months post-treatment. Comparisons at 9 to 12 months follow-up suggested a medium effect from therapy in terms of gambling symptom severity, with no significant differences for other outcomes. One study (n = 18) considered another psychological therapy (i.e.Twelve-Step Facilitated Group Therapy) and suggested beneficial effects in terms of most outcomes at 0 to 3 months post-treatment. The evidence supporting these various classes of therapy ranged from very low to low quality. This review supports the efficacy of CBT in reducing gambling behaviour and other symptoms of pathological and problem gambling immediately following therapy. However, the durability of therapeutic gain is unknown. There is preliminary evidence for some benefits from motivational interviewing therapy in terms of reduced gambling behaviour, although not necessarily other symptoms of pathological and problem gambling. However, the findings are based on few studies and additional research is needed to inform conclusions. There is also evidence suggestive of some possible benefit from integrative therapies, and other psychological therapies for pathological and problem gambling. However, there are too few studies and evidence is insufficient to evaluate these therapies. The majority of studies in this review varied in risk of bias, and much of the evidence comes from studies with multiple limitations. The current data may thus reflect overestimates of treatment efficacy.

Psychological therapies have been proposed for the treatment of pathological and problem gambling, and this review summarised current evidence for these therapies. It included best-quality randomised trials, where therapy was compared with conditions including 'no treatment’ controls or referral to Gamblers Anonymous. It considered categories of therapy including: (1) cognitive-behaviour therapy (CBT); (2) motivational interviewing therapy; (3) integrative therapy; and (4) other psychological therapy. The search identified 14 studies and we combined data from these. Data from nine studies indicated benefits of CBT in the period immediately following treatment. However, there were few studies across longer periods of time (e.g. 12 months) after treatment, and little is known about whether effects of CBT are lasting. Data from three studies of motivational interviewing therapy suggested some benefits in terms of reduced gambling behaviour, but not necessarily other symptoms of pathological and problem gambling. However, the data come from few studies and conclusions regarding motivational interviewing therapy require further research. There were also few studies that provided evidence on integrative therapies (two studies) and other psychological therapies (one study), and there is currently insufficient data to evaluate the efficacy of these therapies

10.1002/14651858.CD008937.pub2

cochrane-simplification-train-2540

cochrane-simplification-train-2540

We included six studies that reported data on 2452 participants with ESKD. Interventions investigated were folic acid with or without other vitamins (vitamin B6, vitamin B12). Participants' mean age was 48 to 65 years, and proportions of male participants ranged from 50% to 98%. Homocysteine-lowering therapy probably leads to little or no effect on cardiovascular mortality (4 studies, 1186 participants: RR 0.93, 95% CI 0.70 to 1.22). There was no evidence of heterogeneity among the included studies (I² = 0%). Homocysteine-lowering therapy had little or no effect on all-cause mortality or any other of this review's secondary outcomes. All prespecified subgroup and sensitivity analyses demonstrated little or no difference. Reported adverse events were mild and there was no increase in the incidence of adverse events from homocysteine-lowering therapies (3 studies, 1248 participants: RR 1.12, 95% CI 0.51 to 2.47; I2 = 0%). Overall, studies were assessed as being at low risk of bias and there was no evidence of publication bias. Homocysteine-lowering therapies were not found to reduce mortality (cardiovascular and all-cause) or cardiovascular events among people with ESKD.

From a search of the literature in January 2016, we identified six randomised controlled trials that involved 2452 participants aged between 48 and 65 years to be analysed. We found that homocysteine-lowering therapies had no benefits for heart health in people with advanced kidney disease who were on dialysis. These therapies did not achieve any reduction in rates of heart disease-related death. However, homocysteine-lowering therapies were generally well tolerated, and had a mild side effect profile. Overall, studies were assessed as high quality.

10.1002/14651858.CD004683.pub4

cochrane-simplification-train-2541

cochrane-simplification-train-2541

Twenty-five trials randomising 4651 people are now included in this review. We chose seven main outcomes of interest for the 'Summary of findings' table. More people allocated haloperidol improved in the first six weeks of treatment than those given placebo (4 RCTs n = 472, RR 0.67 CI 0.56 to 0.80, moderate quality evidence). A further eight trials also found a difference favouring haloperidol across the six weeks to six months period (8 RCTs n = 307 RR 0.67 CI 0.58 to 0.78, moderate quality evidence). Relapse data from two trials favoured haloperidol at < 52 weeks but the evidence was very low quality (2 RCTs n = 70, RR 0.69 CI 0.55 to 0.86). Moderate quality evidence showed about half of those entering studies failed to complete the short trials (six weeks to six months), although, at up to six weeks, 16 studies found a difference that marginally favoured haloperidol (n = 1812, RR 0.87 CI 0.80 to 0.95). Adverse effect data does, nevertheless, support clinical impression that haloperidol is a potent cause of movement disorders, at least in the short term. Moderate quality evidence indicates that haloperidol caused parkinsonism (5 RCTs n = 485, RR 5.48 CI 2.68 to 11.22), akathisia (6 RCTs n = 695, RR 3.66 CI 2.24 to 5.97, and acute dystonia (5 RCTs n = 471, RR 11.49 CI 3.23 to 10.85). Discharge from hospital was equivocal between groups (1 RCT n = 33, RR 0.85 CI 0.47 to 1.52, very low quality evidence). Data were not reported for death and patient satisfaction. Haloperidol is a potent antipsychotic drug but has a high propensity to cause adverse effects. Where there is no treatment option, use of haloperidol to counter the damaging and potentially dangerous consequences of untreated schizophrenia is justified. However, where a choice of drug is available, people with schizophrenia and clinicians may wish to prescribe an alternative antipsychotic with less likelihood of adverse effects such as parkinsonism, akathisia and acute dystonias. Haloperidol should be less favoured as a control drug for randomised trials of new antipsychotics.

The aim of this review was to evaluate the effects of haloperidol for schizophrenia and other similar serious mental illnesses compared with ‘dummy’ or no treatment (placebo). A new search for trials was carried out in May 2012 and the review now includes 25 studies with a total of 4651 people. Review authors rated the quality of evidence reported in the trials for seven main outcomes (global state, death, discharge from hospital, relapse, leaving the study early, adverse effects and satisfaction with treatment). For global state, leaving the study early and adverse effects the reviewers rated the evidence as moderate quality, however, relapse and discharge from hospital were rated to be very low quality evidence. There were no data available for death and satisfaction with treatment. Based on moderate quality evidence, haloperidol was found to be better than placebo in treating schizophrenia. More people given haloperidol improved in the first six weeks of treatment than those given placebo. However, a significant number of people on haloperidol suffered from side effects, including muscle stiffness, uncontrollable shaking, tremors, sleepiness and restlessness. Authors concluded that haloperidol is a potent and effective antipsychotic for treating the symptoms of schizophrenia but has the potential to cause debilitating side effects. People with schizophrenia and psychiatrists may wish to prescribe a newer antipsychotic drug with fewer side effects. Finally, a large proportion of other information and data in the trials were poor and badly reported, meaning that better studies are required. Many people, from both groups left the trials early. This suggests that the design and running of the trials was poor and perhaps not acceptable to people. In light of these findings, it is perhaps surprising that haloperidol is a benchmark antipsychotic in widespread use for treating schizophrenia. It is also surprising that haloperidol is widely used as a comparison for new medication. Haloperidol is an effective antipsychotic drug but has serious and debilitating side effects. Benjamin Gray, Service User and Service User Expert, Rethink Mental Illness.

10.1002/14651858.CD003082.pub3

cochrane-simplification-train-2542

cochrane-simplification-train-2542

The four trials (three USA and one UK) recruited clinically similar groups of babies. Two trials excluded infants with congenital diaphragmatic hernias. In two trials, transfer for ECMO implied transport over long distances. Two trials had follow-up information. One study included economic evaluation. The three USA trials had very small numbers of patients. Two trials used conventional randomisation with low potential for bias. Two used less usual designs, which led to difficulties in their interpretation. All four trials showed strong benefit of ECMO on mortality (typical RR 0.44; 95% CI 0.31 to 0.61), especially for babies without congenital diaphragmatic hernia (typical RR 0.33, 95% CI 0.21 to 0.53). The UK trial provided follow up information about death or severe disability, and cost-effectiveness, and showed benefit of ECMO at one year (RR 0.56, 95% CI 0.40 to 0.78), four years (RR 0.62, 95% CI 0.45 to 0.86), and seven years (RR 0.64, 95% CI 0.47 to 0.86). Overall nearly half of the children recruited had died or were severely disabled by seven years of age, reflecting the severity of their underlying conditions. A policy of ECMO is as cost-effective as other intensive care technologies in common use. A policy of using ECMO in mature infants with severe but potentially reversible respiratory failure results in significantly improved survival without increased risk of severe disability. The benefit of ECMO for babies with diaphragmatic hernia is unclear. Further studies are needed to consider the optimal timing for introducing ECMO; to identify which infants are most likely to benefit; and to address the implications of neonatal ECMO during later childhood and adult life.

In this review, four randomized trials that compared the use of ECMO to the conventional approach to supporting these infants with severe breathing problems were identified. Overall, these trials showed a strong benefit for ECMO regarding survival at the time of hospital discharge. This is particularly true for infants without a specific problem of lung formation (congenital diaphragmatic hernia). The result implies that for every three babies with breathing problems and lung failure who were treated with ECMO rather than conventional ventilation, one more infant will survive. Although little information is available regarding long-term follow-up, one trial in the United Kingdom shows both benefits of ECMO and cost-effectiveness of the use of ECMO.

10.1002/14651858.CD001340.pub2

cochrane-simplification-train-2543

cochrane-simplification-train-2543

We included 12 trials representing 2607 randomised participants. We combined data from six trials in meta-analyses of 1206 randomised participants. The overall RR for reduction in seizure frequency of 50% or more compared to placebo was 1.89 (95% confidence interval (CI) 1.40 to 2.55; 6 trials, 1206 participants; moderate-quality evidence). Dose regression analysis (for trials in adults) showed increasing efficacy with increasing dose, with 25.3% (19.3 to 32.3) of people responding to gabapentin 1800 mg compared to 9.7% on placebo, a 15.5% increase in response rate (8.5 to 22.5). The RR for treatment withdrawal compared to placebo was 1.05 (95% CI 0.74 to 1.49; 6 trials, 1206 participants; moderate-quality evidence). Adverse effects were significantly associated with gabapentin compared to placebo. RRs were as follows: ataxia 2.01 (99% CI 0.98 to 4.11; 3 studies, 787 participants; low-quality evidence), dizziness 2.43 (99% CI 1.44 to 4.12; 6 studies, 1206 participants; moderate-quality evidence), fatigue 1.95 (99% CI 0.99 to 3.82; 5 studies, 1161 participants; low-quality evidence) and somnolence 1.93 (99% CI 1.22 to 3.06; 6 studies, 1206 participants; moderate-quality evidence). There were no significant differences for the adverse effects of headache (RR 0.79, 99% CI 0.46 to 1.35; 6 studies, 1206 participants; moderate-quality evidence) or nausea (RR 0.95, 99% CI 0.52 to 1.73; 4 trials, 1034 participants; moderate-quality evidence). Overall, the studies were rated at low to unclear risk of bias due to information on each risk of bias domain not being available. We judged the overall quality of evidence (using the GRADE approach) as low to moderate due to potential attrition bias resulting from missing outcome data and imprecise results with wide confidence intervals. Gabapentin has efficacy as an add-on treatment in people with drug-resistant focal epilepsy. However, the trials reviewed were of relatively short duration and provide no evidence for the long-term efficacy of gabapentin beyond a three-month period. The results cannot be extrapolated to monotherapy or to people with other epilepsy types.

Data from six of the studies were combined in the analysis. All the participants (including adults and children) were previously taking at least one antiepileptic medicine and all were continuing to have seizures. Either gabapentin (an antiepileptic medicine) or a placebo (a tablet that contains no medicine) was added to the medicine regimen. The results showed that gabapentin effectively reduced seizures when used as an additional treatment. Compared to a placebo, gabapentin was almost twice as likely to reduce seizures by 50% or more. The most common side effects associated with gabapentin ware ataxia (poor co-ordination and unsteady gait), dizziness, fatigue and drowsiness. Overall the quality of evidence was low to moderate as information was not reported for all participants in some of the trials and some of the results were imprecise. Research is needed into the effects of the long-term use of gabapentin. The evidence is current to 20 March 2018.

10.1002/14651858.CD001415.pub3

cochrane-simplification-train-2544

cochrane-simplification-train-2544

Eleven studies, 1592 participants, fulfilled the criteria of inclusion and were included in the review. The studies considered five different psychosocial interventions and two pharmacological treatments (methadone and buprenorphine). Compared to any pharmacological treatment alone, the association of any psychosocial with any pharmacological was shown to significantly reduce dropouts RR 0.71 (95% CI 0.59 to 0.85), use of opiate during the treatment, RR 0.82 (95% CI 0.71 to 0.93), at follow up RR 0.66 (95% IC 0.53 to 0.82) and clinical absences during the treatment RR 0.48 (95%CI 0.38 to 0.59). Moreover, with the evidence currently available, there are no data supporting a single psychosocial approach. Psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in terms of completion of treatment, use of opiate, participants abstinent at follow-up and clinical attendance. The evidence produced by this review is limited due to the small number of participants included in the studies, the heterogeneity of the assessment or the lack of detailed outcome information that prevented the possibility of cumulative analysis for several outcomes. Nevertheless it seems desirable to develop adjunct psychosocial approaches that might make detoxification more effective.

The review authors searched the medical literature and found evidence that providing a psychosocial treatment in addition to pharmacological detoxification treatment to adults who are dependent on heroin use is effective in facilitating opioid detoxification. This conclusion is based on eleven controlled studies involving 1592 adults. The addition of a psychosocial treatment to substitution detoxification treatment improved the number of people who completed treatment (relative risk (RR) 1.47), reduced the use of opiate (RR 0.82), increased abstinence from opiate at follow up (RR 2.43) and halved the number of failures to attend clinic absences (RR 0.48). The findings of an improved rate of clinical attendance may help in suppressing illicit drug use and provides clinical staff with more opportunities to counsel patients in psychiatric, employment and other drug and non-drug related areas. Variations in the populations who are substance users and use of a wide range of different psychosocial interventions means that it is difficult to single out particular therapeutic interventions.

10.1002/14651858.CD005031.pub4

cochrane-simplification-train-2545

cochrane-simplification-train-2545

We included 36 RCTs (8125 women). The quality of the evidence ranged from very low to moderate. The main limitations were risk of bias (associated with poor reporting of methods) and imprecision. Live birth rates: There was insufficient evidence to determine whether there was a difference between rLH combined with rFSH versus rFSH alone in live birth rates (OR 1.32, 95% CI 0.85 to 2.06; n = 499; studies = 4; I2 = 63%, very low-quality evidence). The evidence suggests that if the live birth rate following treatment with rFSH alone is 17% it will be between 15% and 30% using rLH combined with rFSH. OHSS: There may be little or no difference between rLH combined with rFSH versus rFSH alone in OHSS rates (OR 0.38, 95% CI 0.14 to 1.01; n = 2178; studies = 6; I2 = 10%, low-quality evidence). The evidence suggests that if the rate of OHSS following treatment with rFSH alone is 1%, it will be between 0% and 1% using rLH combined with rFSH. Ongoing pregnancy rate: The use of rLH combined with rFSH probably improves ongoing pregnancy rates, compared to rFSH alone (OR 1.20, 95% CI 1.01 to 1.42; participants = 3129; studies = 19; I2 = 2%, moderate-quality evidence). The evidence suggests that if the ongoing pregnancy rate following treatment with rFSH alone is 21%, it will be between 21% and 27% using rLH combined with rFSH. Miscarriage rate: The use of rLH combined with rFSH probably makes little or no difference to miscarriage rates, compared to rFSH alone (OR 0.93, 95% CI 0.63 to 1.36; n = 1711; studies = 13; I2 = 0%, moderate-quality evidence). The evidence suggests that if the miscarriage rate following treatment with rFSH alone is 7%, the miscarriage rate following treatment with rLH combined with rFSH will be between 4% and 9%. Cancellation rates: There may be little or no difference between rLH combined with rFSH versus rFSH alone in rates of cancellation due to low response (OR 0.77, 95% CI 0.54 to 1.10; n = 2251; studies = 11; I2 = 16%, low quality evidence). The evidence suggests that if the risk of cancellation due to low response following treatment with rFSH alone is 7%, it will be between 4% and 7% using rLH combined with rFSH. We are uncertain whether use of rLH combined with rFSH improves rates of cancellation due to imminent OHSS compared to rFSH alone. Use of a fixed effect model suggested a benefit in the combination group (OR 0.60, 95% CI 0.40 to 0.89; n = 2976; studies = 8; I2 = 60%, very low quality evidence) but use of a random effects model did not support the conclusion that there was a difference between the groups (OR 0.82, 95% CI 0.34 to 1.97). We found no clear evidence of a difference between rLH combined with rFSH and rFSH alone in rates of live birth or OHSS. The evidence for these comparisons was of very low-quality for live birth and low quality for OHSS. We found moderate quality evidence that the use of rLH combined with rFSH may lead to more ongoing pregnancies than rFSH alone. There was also moderate-quality evidence suggesting little or no difference between the groups in rates of miscarriage. There was no clear evidence of a difference between the groups in rates of cancellation due to low response or imminent OHSS, but the evidence for these outcomes was of low or very low quality. We conclude that the evidence is insufficient to encourage or discourage stimulation regimens that include rLH combined with rFSH in IVF/ICSI cycles.

We found 36 randomized controlled trials comparing rLH combined with rFSH versus rFSH alone among 8125 women undergoing IVF/ICSI. This is an update of a previous Cochrane Review, first published in 2007. The evidence is current to June 2016. Only seven of the 36 studies clearly stated that they were funded by government or research institutes. Six were funded by pharmaceutical companies and the rest did not state their source of funding. We found no clear evidence of a difference between rLH combined with rFSH and rFSH alone in rates of live birth or OHSS. The evidence for these comparisons was of very low-quality for live birth and low quality for OHSS. We found moderate quality evidence that the use of rLH combined with rFSH may lead to more ongoing pregnancies than rFSH alone. There was also moderate-quality evidence suggesting little or no difference between the groups in rates of miscarriage. There was no clear evidence of a difference between the groups in rates of cancellation due to low response or imminent OHSS, but the evidence for these outcomes was of low or very low quality. We conclude that the evidence is too limited to encourage or discourage stimulation regimens that include rLH combined with rFSH in IVF/ICSI cycles. The quality of the evidence ranged from very low to moderate. The main limitations were risk of bias (associated with poor reporting of methods) and imprecision.

10.1002/14651858.CD005070.pub3

cochrane-simplification-train-2546

cochrane-simplification-train-2546

We found four trials with 271 pregnant women. Three compared methadone with buprenorphine and one methadone with oral slow-release morphine. Three out of four studies had adequate allocation concealment and were double-blind. The major flaw in the included studies was attrition bias: three out of four had a high drop-out rate (30% to 40%) and this was unbalanced between groups. Methadone versus buprenorphine: the drop-out rate from treatment was lower in the methadone group (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.41 to 1.01, three studies, 223 participants). There was no statistically significant difference in the use of primary substance between methadone and buprenorphine (RR 1.81, 95% CI 0.70 to 4.69, two studies, 151 participants). For both, we judged the quality of evidence as low. Birth weight was higher in the buprenorphine group in the two trials that could be pooled (mean difference (MD) -365.45 g (95% CI -673.84 to -57.07), two studies, 150 participants). The third study reported that there was no statistically significant difference. For APGAR score neither of the studies which compared methadone with buprenorphine found a significant difference. For both, we judged the quality of evidence as low. Many measures were used in the studies to assess neonatal abstinence syndrome. The number of newborns treated for neonatal abstinence syndrome, which is the most critical outcome, did not differ significantly between groups. We judged the quality of evidence as very low. Methadone versus slow-release morphine: there was no drop-out in either treatment group. Oral slow-release morphine seemed superior to methadone for abstinence from heroin use during pregnancy (RR 2.40, 95% CI 1.00 to 5.77, one study, 48 participants). We judged the quality of evidence as moderate. Only one study which compared methadone with buprenorphine reported side effects. For the mother there was no statistically significant difference; for the newborns in the buprenorphine group there were significantly fewer serious side effects. In the comparison between methadone and slow-release morphine no side effects were reported for the mother, whereas one child in the methadone group had central apnoea and one child in the morphine group had obstructive apnoea. We did not find sufficient significant differences between methadone and buprenorphine or slow-release morphineto allow us to conclude that one treatment is superior to another for all relevant outcomes. While methadone seems superior in terms of retaining patients in treatment, buprenorphine seems to lead to less severe neonatal abstinence syndrome. Additionally, even though a multi-centre, international trial with 175 pregnant women has recently been completed and its results published and included in this review, the body of evidence is still too small to draw firm conclusions about the equivalence of the treatments compared. There is still a need for randomised controlled trials of adequate sample size comparing different maintenance treatments.

This review found few differences in newborn or maternal outcomes for pregnant, opiate-addicted women who were maintained on methadone, buprenorphine or oral slow-release morphine from a mean gestational age of 23 weeks to delivery. Only four randomised controlled trials with 271 participants trials satisfied the inclusion criteria for the review: two from Austria (outpatients), one from the USA (inpatients) and the fourth a multi-centre, international study conducted in Austria, Canada and the USA. The trials continued for 15 to 18 weeks. Three compared methadone with buprenorphine (223 participants) and one compared methadone with oral slow-release morphine (48 participants). The number of women who dropped out from treatment was lower in the methadone group. However, there was no difference in the use of primary substance between the methadone and buprenorphine groups. The number of newborns treated for neonatal abstinence syndrome did not differ significantly between groups. Birth weight was higher in the buprenorphine group in two trials and no different in the third. Oral slow-release morphine seemed superior to methadone in terms of the number of women who used heroin in their third trimester. However, there was no clear improvement in infant birth weight or duration of neonatal abstinence syndrome. The number of participants in the trials was small and may not be sufficient to draw firm conclusions. All the included studies ended immediately after the baby was born. No severe complications were noted.

10.1002/14651858.CD006318.pub3

cochrane-simplification-train-2547

cochrane-simplification-train-2547

We included four RCTs involving a total of 831 participants who were more than three months poststroke. All RCTs were of MN that applied electrical stimuli to the peroneal nerve. All studies included conditioning protocols to adapt participants to MN use, after which participants used MN from up to eight hours per day to all-day use for ambulation in daily activities performed in the home or community context. All studies compared the use of MN versus another assistive device (ankle-foot orthosis [AFO]). There was a high risk of bias for at least one assessed domain in three of the four included studies. No studies reported outcomes related to independence in ADL. There was low-certainty evidence that AFO was more beneficial than MN on activities involving limbs such as walking speed until six months of device use (mean difference (MD) −0.05 m/s, 95% confidence interval (CI) −0.10 to −0.00; P = 0.03; 605 participants; 2 studies; I2 = 0%; low-certainty evidence); however, this difference was no longer present in our sensitivity analysis (MD −0.07 m/s, 95% CI −0.16 to 0.02; P = 0.13; 110 participants; 1 study; I2 = 0%). There was low to moderate certainty that MN was no more beneficial than AFO on activities involving limbs such as walking speed between 6 and 12 months of device use (MD 0.00 m/s, 95% CI −0.05 to 0.05; P = 0.93; 713 participants; 3 studies; I2 = 17%; low-certainty evidence), Timed Up and Go (MD 0.51 s, 95% CI −4.41 to 5.43; P = 0.84; 692 participants; 2 studies; I2 = 0%; moderate-certainty evidence), and modified Emory Functional Ambulation Profile (MD 14.77 s, 95% CI −12.52 to 42.06; P = 0.29; 605 participants; 2 studies; I2 = 0%; low-certainty evidence). There was no significant difference in walking speed when MN was delivered with surface or implantable electrodes (test for subgroup differences P = 0.09; I2 = 65.1%). For our secondary outcomes, there was very low to moderate certainty that MN was no more beneficial than another assistive device for participation scales of HRQoL (standardized mean difference 0.26, 95% CI −0.22 to 0.74; P = 0.28; 632 participants; 3 studies; I2 = 77%; very low-certainty evidence), exercise capacity (MD −9.03 m, 95% CI −26.87 to 8.81; P = 0.32; 692 participants; 2 studies; I2 = 0%; low-certainty evidence), and balance (MD −0.34, 95% CI −1.96 to 1.28; P = 0.68; 692 participants; 2 studies; I2 = 0%; moderate-certainty evidence). Although there was low- to moderate-certainty evidence that the use of MN did not increase the number of serious adverse events related to intervention (risk ratio (RR) 0.35, 95% CI 0.04 to 3.33; P = 0.36; 692 participants; 2 studies; I2 = 0%; low-certainty evidence) or number of falls (RR 1.20, 95% CI 0.92 to 1.55; P = 0.08; 802 participants; 3 studies; I2 = 33%; moderate-certainty evidence), there was low-certainty evidence that the use of MN in people after stroke may increase the risk of participants dropping out during the intervention (RR 1.48, 95% CI 1.11 to 1.97; P = 0.007; 829 participants; 4 studies; I2 = 0%). Current evidence indicates that MN is no more beneficial than another assistive technology device for improving activities involving limbs measured by Timed Up and Go, balance (moderate-certainty evidence), activities involving limbs measured by walking speed and modified Emory Functional Ambulation Profile, exercise capacity (low-certainty evidence), and participation scale of HRQoL (very low-certainty evidence). Evidence was insufficient to estimate the effect of MN on independence in ADL. In comparison to other assistive devices, MN does not appear to increase the number of falls (moderate-certainty evidence) or serious adverse events (low-certainty evidence), but may result in a higher number of dropouts during intervention period (low-certainty evidence).

We found four studies of MN involving a total of 831 participants who more than three months poststroke, with mean ages from 53 to 64 years. All participants were able to walk from less than 0.5 m/s to more than 0.7 or even 0.9 m/s. The included studies were published between 2007 and 2015 in the USA and the Netherlands. All included studies applied MN directed to a nerve in the leg (peroneal nerve) to promote the contraction of a muscle at the front of the leg, thus preventing the foot 'dropping' as the leg was swung forward while the participant walked. MN was used from up to eight hours per day to all-day use for walking about in the natural environment in which people live. Three studies used an MN device that interfaces with the nervous system through electrodes positioned over the skin in the projection of the peroneal nerve in the leg. Only one study used a implantable device whose electrical stimulus is released directly on the nerve by electrodes placed under the layer that surrounds the nerve. All studies compared MN versus ankle-foot orthosis (AFO), that is an assistive device usually made of a rigid material and placed externally on the lower leg to hold the foot and ankle to prevent the foot dropping. There is limited evidence that people after stroke who receive MN as an orthosis for walking in the home or community context may not improve activities involving limbs such as walking speed between 6 and 12 months of device use (low-certainty evidence), Timed Up and Go (moderate-certainty evidence), and modified Emory Functional Ambulation Profile (low-certainty evidence); as well as participation scale of health-related quality of life (very low-certainty evidence), exercise capacity (low-certainty evidence), and balance (moderate-certainty evidence), compared with people after stroke who receive AFO. There was evidence of an effect that the control intervention (AFO) attained a higher walking speed after six months of device use (low-certainty evidence), but this evidence showed that the improvements were too small to indicate a meaningful change to patients, and when we excluded the study in which the people that assessed the outcomes were aware of the intervention details, this effect was no longer found. There was no difference in effects on walking speed between MN with surface versus MN with implantable electrodes. No study reported outcomes related to independence in activities of daily living. The majority of studies reported adverse events such as falls and serious adverse events related to device use, which were found to be similar for MN and AFO use (moderate- and low-certainty evidence, respectively). One study considered serious adverse events related to device use as serious falls. More people who received MN withdrew from the studies than did people who received AFO (low-certainty evidence). The results of this review indicate that little is known about the effects of MN and that further information is required. It is unknown if people less than three months poststroke could benefit from MN use as an assistive device to perform activities in daily life. The impact of MN applied to the upper limb or MN that uses brain or muscle signals to trigger the stimulation is unknown in people with stroke. We found no evidence evaluating the costs of delivering MN. The certainty of the evidence ranged from moderate to very low.

10.1002/14651858.CD012991.pub2

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cochrane-simplification-train-2548

Eleven studies met our eligibility criteria and all were at medium or high risk of bias. Only five studies gave the total number of participants (totalling 7372 participants). Three studies used a randomised design, with the others using pre-post comparisons. Several different strategies were investigated. Four studies examined the impact of additional visits or information for the study site, with no increases in recruitment demonstrated. Increased recruitment rates were reported in two studies that used a dedicated clinical recruiter, and five studies that introduced an automated alert system for identifying eligible participants. The studies were embedded into trials evaluating care in oncology mainly but also in emergency departments, diabetes and lower back pain. There is no strong evidence for any single strategy to help healthcare professionals to recruit participants in research studies. Additional visits or information did not appear to increase recruitment by healthcare professionals. The most promising strategies appear to be those with a dedicated resource (e.g. a clinical recruiter or automated alert system) for identifying suitable participants that reduced the demand on healthcare professionals, but these were assessed in studies at high risk of bias.

We found 11 studies that assessed recruitment strategies used with healthcare staff in search of the literature in January 2015. Five included the total number of participants (7372). There were three main strategies: 1. Using an alert system, either a computer system or member of staff to check patient records, to alert staff recruiting participants that someone might be suitable for the study (five studies). 2. Giving additional information about the study to the staff at hospitals or clinics who are recruiting people through visits from the researchers, educational seminars or leaflets (four studies). 3. Using a designated member of staff whose primary role was to recruit participants (two studies). All the studies identified were of quite low quality, so it is difficult to draw firm conclusions from them. Five studies examined the alert system to identify participants who might be suitable for a study. Alert systems showed some promising results but were not unanimous in their findings. The four studies that evaluated the provision of additional information, visits or education to the sites recruiting participants found that none of the tested strategies led to improved recruitment. The most promising strategy appears to be the employment of someone such as a clinical trials officer or research nurse with the specific task of recruiting participants to research studies. The two studies using this strategy showed improvement in recruitment rates but both were at high risk of bias. More research is still needed to evaluate the role of a designated person to recruit to research studies.

10.1002/14651858.MR000036.pub2

cochrane-simplification-train-2549

cochrane-simplification-train-2549

Eleven studies (3912 participants) met the inclusion criteria of the review. Small benefits of ipratropium over a short-acting beta-2 agonist were demonstrated on lung function outcomes. There were small benefits in favour of ipratropium on quality of life (HRQL), as well as a reduction in the requirement for oral steroids. Combination therapy with ipratropium plus a short-acting beta-2 agonist conferred benefits over a short-acting beta-2 agonist alone in terms of post-bronchodilator lung function. There was no significant benefit of combination therapy in subjective improvements in HRQL, but again there was a reduction in the requirement for oral steroids. The available data from the trials included in this review suggest that the advantage of regular long term use of ipratropium alone or in combination with a short-acting beta-2 agonist or over a beta-2 agonist alone are small, if the aim is to improve lung function, symptoms and exercise tolerance. Until further data are available, the strategy of providing a short-acting beta-2 agonist on a PRN basis, and then either continuing with the short-acting beta-2 agonist regularly or conducting an "n of 1" trial of regular beta-2 agonist or regular anticholinergic to determine the treatment that gives the best relief of symptoms (and continuing with it), would seem cost effective. This strategy does need formal evaluation. Patient preference is also important, as is the relative importance of avoiding the use of systemic corticosteroids.

This review looks at studies that compare the regular use for at least four weeks of different types of inhaled short-acting bronchodilator medication in people with chronic obstructive pulmonary disease (COPD, or emphysema/chronic bronchitis). There were eleven trials included. There were no major differences seen between the responses to ipratropium and salbutamol, or the combination. Where there were benefits, they were small and would not support a general recommendation for the use of ipratropium bromide or a combination with beta-2 agonist over a beta-2 agonist alone in COPD. People with COPD could use the short-acting bronchodilator that gives them the most improvement in their symptoms.

10.1002/14651858.CD001387.pub2

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cochrane-simplification-train-2550

We located 23 studies: two RCTs with 1414 workplaces, two CBAs with 9903 workplaces, one ITS with six outcome measurements, 12 panel studies and six qualitative studies with 310 participants. Studies evaluated the effects of inspections in general and the effects of their consequences, such as penalties. Studies on the effects of prosecution, warnings or closure were not available or were of such quality that we could not include their results. The effect was measured on injury rates, on exposure to physical workload and on compliance with regulation, with a follow-up varying from one to four years. All studies had serious limitations and therefore the quality of the evidence was low to very low. The injury rates in the control groups varied across studies from 1 to 23 injuries per 100 person-years and compliance rates varied from 40% to 75% being compliant. The effects of inspections were inconsistent in seven studies: injury rates decreased or stayed at a similar level compared to no intervention at short and medium-term follow-up. In studies that found a decrease the effect was small with a 10% decrease of the injury rate. At long-term follow-up, in one study there was a significant decrease of 23% (95% confidence interval 8% to 23%) in injury rates and in another study a substantial decrease in accident rates, both compared to no intervention. First inspections, follow-up inspections, complaint and accident inspections resulted in higher compliance rates compared to the average effect of any other type of inspections. In small firms, inspections with citations or with more penalties could result in fewer injuries or more compliance in the short term but not in the medium term. Longer inspections and more frequent inspections probably do not result in more compliance. In two studies, there was no adverse effect of inspections on firm survival, employment or sales. Qualitative studies show that there is support for enforcement among workers. However, workers doubt if the inspections are effective because inspections are rare and violations can be temporarily fixed to mislead inspectors. There is evidence that inspections decrease injuries in the long term but not in the short term. The magnitude of the effect is uncertain. There are no studies that used chemical or physical exposures as outcome. Specific, focused inspections could have larger effects than inspections in general. The effect of fines and penalties is uncertain. The quality of the evidence is low to very low and therefore these conclusions are tentative and can be easily changed by better future studies. There is an urgent need for better designed evaluations, such as pragmatic randomised trials, to establish the effects of existing and novel enforcement methods, especially on exposure and disorders.

We found 23 studies. Two studies were randomised controlled trials with 1414 workplaces. Fifteen non-randomised studies analysed injury rates of firms obtained from large administrative databases. Six studies with more than 340 participants in total reported on the opinions of workers or employers. Two studies randomly allocated inspections or no inspections to workplaces. After one year follow-up the non-fatal injury rate in one study and the frequency of physical overload in the other study were still similar in both study groups. Another five similar but lower quality studies had inconsistent results at short and medium-term follow-up. Two other non-randomised studies found that after more than three years inspections decreased injuries and accidents by 23% compared to no inspections and there was no effect on the firms' productivity. Specific inspections resulted in higher compliance rates. Inspections with penalties could result in fewer injuries and more compliance in the short term in small firms. Longer inspections and more frequent inspections probably do not result in more compliance. Two studies did not find a harmful effect of inspections on firm lifetime or employment. Qualitative studies showed that there is support for enforcement among workers. However, workers doubt if inspections are effective because they are rare and violations can be temporarily fixed to mislead the inspectors. We concluded that inspections decrease injuries in the long term but probably not in the short term. The evidence is of low to very low quality because the results across studies are inconsistent and studies are observational and do not take into account other factors that could affect the results. In addition, the magnitude of the effect is uncertain because it varies from a 3 to 23 per cent decrease in injury rates. Because the quality of the evidence is low, future studies can easily change our conclusions. There is an urgent need for large-scale randomised trials to evaluate different types of inspection methods on exposure, disorders and injuries.

10.1002/14651858.CD010183.pub2

cochrane-simplification-train-2551

cochrane-simplification-train-2551

Nine studies with 658 infants fulfilled the inclusion criteria. Term and preterm infants with Rh or ABO (or both) incompatibility were included. The use of exchange transfusion decreased significantly in the immunoglobulin treated group (typical RR 0.35, 95% CI 0.25 to 0.49; typical RD -0.22, 95% CI -0.27 to -0.16; NNTB 5). The mean number of exchange transfusions per infant was also significantly lower in the immunoglobulin treated group (MD -0.34, 95% CI -0.50 to -0.17). However, sensitivity analysis by risk of bias showed that in the only two studies in which the treatment was masked by use of a placebo and outcome assessment was blinded, the results differed; there was no difference in the need for exchange transfusions (RR 0.98, 95% CI 0.48 to 1.98) or number of exchange transfusions (MD -0.04, 95% CI -0.18 to 0.10). Two studies assessed long-term outcomes and found no cases of kernicterus, deafness or cerebral palsy. Although overall results show a significant reduction in the need for exchange transfusion in infants treated with IVIg, the applicability of the results is limited because of low to very low quality of evidence. Furthermore, the two studies at lowest risk of bias show no benefit of IVIg in reducing the need for and number of exchange transfusions. Based on these results, we have insufficient confidence in the effect estimate for benefit of IVIg to make even a weak recommendation for the use of IVIg for the treatment of alloimmune HDN. Further studies are needed before the use of IVIg for the treatment of alloimmune HDN can be recommended, and should include blinding of the intervention by use of a placebo as well as sufficient sample size to assess the potential for serious adverse effects.

We searched the medical literature to 19 May 2017 and found nine randomized (clinical studies where people are randomly put into one of two or more treatment groups) or partly (quasi) randomized trials (including 658 participants) that assessed the efficiency of IVIg in infants with alloimmune HDN. Analysis of all included studies showed a reduction in the need for and number of ETs in infants treated with IVIg combined with phototherapy compared to infants treated with phototherapy only. However, this was not confirmed in an analysis of the two placebo-controlled studies (where a pretend treatment was given). There was no difference in the need for or number of top-up transfusions. The evidence from the studies was very low quality. However, two studies used a placebo, thereby minimizing bias and allowing blinding of the researchers assessing the response. These studies were consistent with each other and yielded moderate quality evidence (with a relatively small total number of participants involved (172) being the only reason to not regard the level of evidence from them as high) that IVIg was ineffective in preventing ET or top-up transfusions. Based on all included studies, we could make no conclusions on the benefit of IVIg in preventing ET or top-up transfusion. However, the two placebo-controlled trials provided evidence of moderate quality that IVIg was ineffective in preventing ET or top-up transfusion, and therefore routine use in alloimmune HDN should not be recommended. However, since there was some evidence that IVIg reduced hemolysis (in laboratory studies), future high-quality studies are needed to determine whether IVIg has limited role in some infants with alloimmune HDN.

10.1002/14651858.CD003313.pub2

cochrane-simplification-train-2552

cochrane-simplification-train-2552

Of 493 records that we identified from databases as a result of the search (excluding duplicates), we regarded 70 abstracts/titles as potentially relevant studies. Independent scrutiny of these 70 titles and abstracts identified 29 potentially relevant studies. Of the 29 potentially relevant studies, one study met the criteria for inclusion. This study was a RCT that compared participants undergoing RSI and endotracheal intubation in the context of elective surgery requiring a general anaesthetic. Forty participants were recruited, 20 of whom had cricoid pressure applied and 20 of whom had cricoid pressure simulated. The main outcomes reported were systolic arterial pressure and heart rate after laryngoscopy and tracheal intubation. We did not consider these outcomes relevant for the purposes of this systematic review. The search also identified one study that could potentially be included in an updated systematic review in the future, but was at the time of the search a proposal for a trial only and had no reported outcomes at this time. There is currently no information available from published RCTs on clinically relevant outcome measures with respect to the application of cricoid pressure during RSI in the context of endotracheal intubation. On the basis of the findings of non-RCT literature, however, cricoid pressure may not be necessary to undertake RSI safely, and therefore well-designed and conducted RCTs should nonetheless be encouraged to properly assess the safety and effectiveness of cricoid pressure.

Our search strategy was designed to identify randomized controlled trials (RCTs) where RSI was undertaken to secure an artificial airway for a general anaesthetic with or without the application of cricoid pressure. Vomiting or regurgitation of stomach contents during anaesthesia was to be assessed either by looking directly down the airway or by various laboratory and imaging (radiological) methods. We also set out to determine whether applying cricoid pressure caused any harm. We searched the databases until May 2015. Only one RCT met our inclusion criteria but unfortunately this trial did not report on any clinically relevant results. We classified one other trial as ongoing. The researchers have reported on their planned protocol for the clinical trial, where cricoid pressure applied using a measured force will be compared with cricoid pressure without measuring the force applied. The number of patients who vomit is to be monitored. This systematic review shows an absence of evidence regarding the effectiveness and risks of cricoid pressure during RSI for intubation. Little can be said therefore about whether this technique should be continued in clinical practice. One current ongoing study shows promise that it will provide useful information in the future.

10.1002/14651858.CD011656.pub2

cochrane-simplification-train-2553

cochrane-simplification-train-2553

We included seven studies from the earlier review and two new studies (nine studies, 649 participants) of 6 to 24 weeks' duration, enrolling between 22 and 208 participants; none had 50 or more participants in each treatment arm. Two studies used a cross-over design. The daily dose of amitriptyline was 25 mg to 50 mg, and some studies had an initial titration period. There was no first or second tier evidence for amitriptyline in the treatment of fibromyalgia. Using third tier evidence the risk ratio (RR) for at least 50% pain relief, or equivalent, with amitriptyline compared with placebo was 3.0 (95% confidence interval (CI) 1.7 to 4.9), with an NNT) of 4.1 (2.9 to 6.7) (very low quality evidence). There were no consistent differences between amitriptyline and placebo or other active comparators for relief of symptoms such as fatigue, poor sleep, quality of life, or tender points. More participants experienced at least one adverse event with amitriptyline (78%) than with placebo (47%). The RR was 1.5 (1.3 to 1.8) and the NNH was 3.3 (2.5 to 4.9). Adverse event and all-cause withdrawals were not different, but lack of efficacy withdrawals were more common with placebo (12% versus 5%; RR 0.42 (0.19 to 0.95)) (very low quality evidence). Amitriptyline has been a first-line treatment for fibromyalgia for many years. The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing, but has to be balanced against years of successful treatment in many patients with fibromyalgia. There is no good evidence of a lack of effect; rather our concern should be of overestimation of treatment effect. Amitriptyline will be one option in the treatment of fibromyalgia, while recognising that only a minority of patients will achieve satisfactory pain relief. It is unlikely that any large randomised trials of amitriptyline will be conducted in fibromyalgia to establish efficacy statistically, or measure the size of the effect.

In March 2015 we performed searches to look for new studies, and found only two additional small studies to include. Neither provided any good quality evidence for benefit or harm. There were still no studies that could provide an answer that was trustworthy or reliable, because most were relatively old, and used methods or reported results that we now recognise as making benefits seem better than they are. This is disappointing, but we can still make useful comments about the drug. Amitriptyline probably does provide good levels of pain relief for some people with fibromyalgia, although we cannot be certain of this. Our best guess is that amitriptyline provides good pain relief in about 1 in 4 (25%) more people than does placebo. About 1 in 3 (31%) more people than with placebo report having one or more adverse events, which are usually not serious but may be troublesome and interfere with taking the treatment. We cannot trust either figure based on the information available. The most important message is that amitriptyline probably does give really good pain relief to some patients with fibromyalgia, but only a minority of them; amitriptyline will not work for most people.

10.1002/14651858.CD011824

cochrane-simplification-train-2554

cochrane-simplification-train-2554

Eight studies met our inclusion criteria: three RCTs and five ITS studies involving a total of 135 general practices/primary care clinics, seven hospitals and one outpatient clinic. The studies were heterogeneous in terms of types of interventions, elective procedures and clinical conditions; this made meta-analysis unfeasible. One ITS study evaluating prioritisation of demand through a system for streamlining elective surgery services reduced the number of semi-urgent participants waiting longer than the recommended time (< 90 days) by 28 participants/mo, while no effects were found for urgent (< 30 days) versus non-urgent participants (< 365 days). Interventions aimed at restructuring the intake assessment/referral process were evaluated in seven studies. Four studies (two RCTs and two ITSs) evaluated open access, or direct booking/referral: One RCT, which showed that open access to laparoscopic sterilisation reduced waiting times, had very high attrition (87%); the other RCT showed that open access to investigative services reduced waiting times (30%) for participants with lower urinary tract syndrome (LUTS) but had no effect on waiting times for participants with microscopic haematuria. In one ITS study, same-day scheduling for paediatric health clinic appointments reduced waiting times (direct reduction of 25.2 days, and thereafter a decrease of 3.03 days per month), while another ITS study showed no effect of a direct booking system on proportions of participants receiving a colposcopy appointment within the recommended time. One RCT and one ITS showed no effect of distant consultancy (instant photography for dermatological conditions and telemedicine for ear nose throat (ENT) conditions) on waiting times; another ITS study showed no effect of a pooled waiting list on the number of participants waiting for uncomplicated spinal surgery. Overall quality of the evidence for all outcomes, assessed using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) tool, ranged from low to very low. We found no studies evaluating interventions to increase capacity or to ration demand. As only a handful of low-quality studies are presently available, we cannot draw any firm conclusions about the effectiveness of the evaluated interventions in reducing waiting times. However, interventions involving the provision of more accessible services (open access or direct booking/referral) show some promise.

We reviewed the evidence on the effects of interventions in reducing waiting times. We found eight eligible studies (three randomised controlled trials and five interrupted time series studies) involving 135 primary care clinics, seven hospitals and one outpatient clinic. Different interventions, elective procedures and clinical conditions across included studies made pooling of data unfeasible. The quality of the included evidence (to November 2013) ranged from low to very low, as data were obtained from randomised controlled trials that for the most part suffered from serious bias, and from non-randomised studies without a control group. The single study that evaluated an intervention aimed at prioritising demand showed that introducing a system for streamlining elective surgery reduced the number of semi-urgent patients waiting longer than recommended, but did not affect urgent or non-urgent groups. Seven studies evaluated interventions aimed at restructuring the intake assessment/referral process. Three of four studies evaluating effects of open access or direct booking/referral showed beneficial effects: One study showed reduced waiting times for open access to sterilisation through keyhole surgery; another showed that open access to investigative services may lead to reduced waiting times for patients with urinary symptoms (but not for patients with microscopic blood in urine); and one study reported that same-day scheduling reduced waiting times for those seeking child health outpatient services. One study showed no effect of a direct booking system on the proportion of patients reported to have moderate or severe cell changes on the neck of the womb who received an appointment for further investigation within four weeks. Two studies of distant consultancy (instant photography for skin conditions and telemedicine for ear, nose and throat conditions) showed no effect on waiting times to see a specialist. One study reported that using a pooled waiting list did not change the number of patients waiting for routine back surgery within the recommended time. We found no studies evaluating interventions aimed at increasing capacity or rationing demand. As only a handful of low-quality studies are presently available, we cannot draw any firm conclusions about the effectiveness of the evaluated interventions in reducing waiting times. However, interventions involving the provision of more accessible services (open access or direct booking/referral) show some promise.

10.1002/14651858.CD005610.pub2

cochrane-simplification-train-2555

cochrane-simplification-train-2555

We included 42 studies addressing chemotherapy in 9463 patients with advanced pancreatic cancer. We did not identify any eligible studies on radiotherapy. We did not find any benefit for chemotherapy over best supportive care. However, two identified studies did not have sufficient data to be included in the analysis, and many of the chemotherapy regimens studied were outdated. Compared to gemcitabine alone, participants receiving 5FU had worse OS (HR 1.69, 95% CI 1.26 to 2.27, moderate-quality evidence), PFS (HR 1.47, 95% CI 1.12 to 1.92) and QoL. On the other hand, two studies showed FOLFIRINOX was better than gemcitabine for OS (HR 0.51 95% CI 0.43 to 0.60, moderate-quality evidence), PFS (HR 0.46, 95% CI 0.38 to 0.57) and response rates (RR 3.38, 95% CI 2.01 to 5.65), but it increased the rate of side effects. The studies evaluating CO-101, ZD9331 and exatecan did not show benefit or harm when compared with gemcitabine alone. Giving gemcitabine at a fixed dose rate improved OS (HR 0.79, 95% CI 0.66 to 0.94, high-quality evidence) but increased the rate of side effects when compared with bolus dosing. When comparing gemcitabine combinations to gemcitabine alone, gemcitabine plus platinum improved PFS (HR 0.80, 95% CI 0.68 to 0.95) and response rates (RR 1.48, 95% CI 1.11 to 1.98) but not OS (HR 0.94, 95% CI 0.81 to 1.08, low-quality evidence). The rate of side effects increased. Gemcitabine plus fluoropyrimidine improved OS (HR 0.88, 95% CI 0.81 to 0.95), PFS (HR 0.79, 95% CI 0.72 to 0.87) and response rates (RR 1.78, 95% CI 1.29 to 2.47, high-quality evidence), but it also increased side effects. Gemcitabine plus topoisomerase inhibitor did not improve survival outcomes but did increase toxicity. One study demonstrated that gemcitabine plus nab-paclitaxel improved OS (HR 0.72, 95% CI 0.62 to 0.84, high-quality evidence), PFS (HR 0.69, 95% CI 0.58 to 0.82) and response rates (RR 3.29, 95% CI 2.24 to 4.84) but increased side effects. Gemcitabine-containing multi-drug combinations (GEMOXEL or cisplatin/epirubicin/5FU/gemcitabine) improved OS (HR 0.55, 95% CI 0.39 to 0.79, low-quality evidence), PFS (HR 0.43, 95% CI 0.30 to 0.62) and QOL. We did not find any survival advantages when comparing 5FU combinations to 5FU alone. Combination chemotherapy has recently overtaken the long-standing gemcitabine as the standard of care. FOLFIRINOX and gemcitabine plus nab-paclitaxel are highly efficacious, but our analysis shows that other combination regimens also offer a benefit. Selection of the most appropriate chemotherapy for individual patients still remains difficult, with clinicopathological stratification remaining elusive. Biomarker development is essential to help rationalise treatment selection for patients.

We looked for all studies in people with pancreatic cancer that could not be operated on (locally advanced) or that had already spread beyond the pancreas (metastatic). We found 42 clinical studies involving 9463 participants who were receiving their first therapy for PC. Our search is current to June 2017. The studies compared one therapy against either best supportive care (symptom management only) or another type of therapy. Studies had to evaluate overall survival (or time to death). The study could be testing either chemotherapy (drugs that kill or slow the growth of cancer cells) or radiotherapy (X-ray treatment). We collected data on survival, tumour response rate, side effects and quality of life. The results of clinical studies addressing targeted/biological therapies, immunotherapies, second-line therapies and local treatments for locally advanced disease will be reported in a separate Cochrane Review. This review has shown that in advanced disease, combination chemotherapy with FOLFIRINOX (5-fluorouracil, irinotecan, oxaliplatin combination); GEMOXEL (gemcitabine, oxaliplatin and capecitabine); cisplatin/epirubicin/5FU/gemcitabine; gemcitabine plus nab-paclitaxel; and gemcitabine plus a fluoropyrimidine agent, provide a survival advantage over gemcitabine alone. These combinations do increase side effects. Gemcitabine given slowly using a fixed rate of infusion may be more effective than giving it in the standard way, which is quickly over 30 minutes. The quality of the evidence varied greatly amongst comparisons. The highest quality evidence was for gemcitabine versus fixed dose rate gemcitabine and some of the gemcitabine combinations (fluoropyrimidine, topoisomerase, and taxane). We judged the studies for quality using factors like how well they were conducted, how well they reported results and whether they used a placebo.

10.1002/14651858.CD011044.pub2

cochrane-simplification-train-2556

cochrane-simplification-train-2556

Twenty-two studies (3215 participants) were included. The majority of studies enrolled patients with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded patients with severe CDI and few patients with severe CDI were included in the other six studies. Twelve different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin, bacitracin, cadazolid, LFF517, surotomycin and fidaxomicin. Most of the studies were active comparator studies comparing vancomycin with other antibiotics. One small study compared vancomycin to placebo. There were no other studies that compared antibiotic treatment to a placebo or a 'no treatment' control group. The risk of bias was rated as high for 17 of 22 included studies. Vancomycin was found to be more effective than metronidazole for achieving symptomatic cure. Seventy-two per cent (318/444) of metronidazole patients achieved symptomatic cure compared to 79% (339/428) of vancomycin patients (RR 0.90, 95% CI 0.84 to 0.97; moderate quality evidence). Fidaxomicin was found to be more effective than vancomycin for achieving symptomatic cure. Seventy-one per cent (407/572) of fidaxomicin patients achieved symptomatic cure compared to 61% (361/592) of vancomycin patients (RR 1.17, 95% CI 1.04 to 1.31; moderate quality evidence). Teicoplanin may be more effective than vancomycin for achieving a symptomatic cure. Eightly-seven per cent (48/55) of teicoplanin patients achieved symptomatic cure compared to 73% (40/55) of vancomycin patients (RR 1.21, 95% CI 1.00 to 1.46; very low quality evidence). For other comparisons including the one placebo-controlled study the quality of evidence was low or very low due to imprecision and in many cases high risk of bias because of attrition and lack of blinding. One hundred and forty deaths were reported in the studies, all of which were attributed by study authors to the co-morbidities of the participants that lead to acquiring CDI. Although many other adverse events were reported during therapy, these were attributed to the participants' co-morbidities. The only adverse events directly attributed to study medication were rare nausea and transient elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13 (Health Warehouse). Vancomycin 125 mg costs USD 1779 (Walgreens for 56 tablets) compared to fidaxomicin 200 mg at USD 3453.83 or more (Optimer Pharmaceuticals) and teicoplanin at approximately USD 83.67 (GBP 71.40, British National Formulary). No firm conclusions can be drawn regarding the efficacy of antibiotic treatment in severe CDI as most studies excluded patients with severe disease. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the initiating antibiotic. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other two antibiotics. The quality of evidence for teicoplanin is very low. Adequately powered studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin, would be of interest.

We searched the medical literature up to 26 January 2017. All randomised trials that compare two different antibiotics, or variations in dosing of a single antibiotic for treatment of CDI were included. Trials comparing antibiotic to placebo (e.g. a sugar pill) or no treatment were sought but, save for one poor quality placebo-controlled trial, none were found. Trials that compared antibiotics to a non-antibiotic treatment were not included. Results Twenty-two studies (total 3215 participants) were included. The majority of studies enrolled participants with mild to moderate CDI who could tolerate oral antibiotics. Sixteen of the included studies excluded participants with severe CDI and few participants with severe CDI were included in the other studies. Twelve different antibiotics were assessed. Most of the studies compared vancomycin or metronidazole with other antibiotics. One small study compared vancomycin to placebo (e.g. sugar pill). There were no other studies that compared antibiotic treatment to a placebo or a no treatment control group. Seventeen of the 22 included studies had quality issues. In four studies, vancomycin was found to be superior to metronidazole for achieving sustained symptomatic cure (defined as resolution of diarrhoea and no recurrence of CDI). We rated the quality of the evidence supporting this finding as moderate. A new antibiotic, fidaxomicin, was, in two large studies, found to be superior to vancomycin. The quality of the evidence supporting this finding was moderate. It should be noted that the differences in effectiveness between these antibiotics were not too great and that metronidazole is far less expensive than either vancomycin and fidaxomicin. A pooled analysis of two small studies suggests that teicoplanin may be more effective than vancomycin for achieving symptomatic cure. The quality of the evidence supporting this finding was very low. The quality of the evidence for the other seven antibiotics in this review was very poor because the studies were very small, and many patients dropped out of these studies before completion. One hundred and forty deaths were reported in the studies, all of which were attributed to participants preexisting health problems. The only side effects attributed to antibiotics were rare nausea and temporary elevation of liver enzymes. Recent cost data (July 2016) for a 10 day course of treatment shows that metronidazole 500 mg is the least expensive antibiotic with a cost of USD 13. Vancomycin 125 mg costs USD 1779 compared to fidaxomicin 200 mg at USD 3453.83 or more and teicoplanin at approximately USD 83.67. Conclusion No firm conclusions can be drawn regarding the effectiveness of antibiotic treatment in severe CDI as most studies excluded these patients. The lack of any 'no treatment' control studies does not allow for any conclusions regarding the need for antibiotic treatment in patients with mild CDI beyond withdrawal of the antibiotic that caused CDI. Nonetheless, moderate quality evidence suggests that vancomycin is superior to metronidazole and fidaxomicin is superior to vancomycin. The differences in effectiveness between these antibiotics were not too large and the advantage of metronidazole is its far lower cost compared to the other antibiotics. The quality of evidence for teicoplanin is very low. Larger studies are needed to determine if teicoplanin performs as well as the other antibiotics. A trial comparing the two cheapest antibiotics, metronidazole and teicoplanin would be of interest.

10.1002/14651858.CD004610.pub5

cochrane-simplification-train-2557

cochrane-simplification-train-2557

We identified 6600 references (4647 references in our initial review) and included 10 trials (3575 participants). Follow-up ranged from 30 days to one year. Nine trials provided mortality data (3218 participants, 466 events), with a risk ratio of 1.02 (95% CI 0.87 to 1.19) (low-certainty evidence). Seven trials provided hospital readmission data (2843 participants, 1043 events) with a risk ratio of 0.95 (95% CI 0.87 to 1.04) (high-certainty evidence). Four trials provided emergency department contact data (1442 participants, 244 events) with a risk ratio of 0.73 (95% CI 0.52 to 1.03) (low-certainty evidence). The estimated reduction in emergency department contacts of 27% (with a CI ranging from 48% reduction to 3% increase in contacts) corresponds to a number needed to treat for an additional beneficial outcome of 37 for a low-risk population and 12 for a high-risk population over one year. Subgroup and sensitivity analyses did not significantly alter our results. We found no evidence that medication review reduces mortality or hospital readmissions, although we did find evidence that medication review may reduce emergency department contacts. However, because of short follow-up ranging from 30 days to one year, important treatment effects may have been overlooked. High-quality trials with long-term follow-up (i.e. at least up to a year) are needed to provide more definitive evidence for the effect of medication review on clinically important outcomes such as mortality, readmissions and emergency department contacts, and on outcomes such as adverse events. Therefore, if used in clinical practice, medication reviews should be undertaken as part of a clinical trial with long-term follow-up.

We included 10 randomised controlled trials with a total of 3575 participants. We found that medication review does not seem to prevent death and hospital readmissions, but that it might reduce emergency department contacts. Our confidence in results across studies ranged from low to high. We found no evidence that medication review in hospitalised patients makes a difference towards preventing mortality (low-certainty evidence) or hospital readmissions (high-certainty evidence), but we found that medication review may have a preventive effect on reducing the number of emergency department contacts (low-certainty evidence). In the included trials, participants were followed for a short time (ranging from 30 days to one year). Therefore, important long-term treatment effects may have been overlooked. We suggest that further research with long-term patient follow-up and examination of specific methods of medication review should be undertaken before this intervention is implemented in clinical practice.

10.1002/14651858.CD008986.pub3

cochrane-simplification-train-2558

cochrane-simplification-train-2558

Of 39 identified studies, four met the criteria for inclusion. Two of the included studies reported a significant decrease in paediatric burn and scald injury in the intervention compared with the control communities. The failure of the other two studies to show a positive result may have been due to limited time-frame for the intervention and/or failure to adequately implement the counter-measures in the communities. There are a very limited number of research studies allowing conclusions to be drawn about the effectiveness of community-based injury prevention programmes to prevent burns and scalds in children. There is a pressing need to evaluate high-quality community-based intervention programmes based on efficacious counter-measures to reduce burns and scalds in children. It is important that a framework for considering the problem of burns and scalds in children from a prevention perspective be articulated, and that an evidence-based suite of interventions be combined to create programme guidelines suitable for implementation in communities throughout the world.

The efficacy of this approach is difficult to assess and there have been few research studies of good quality. The current review sought to review studies evaluating the success of community-based programmes specifically intended to reduce burn and scald injury in children. Only four studies were identified that met the inclusion criteria and two of these found a reduction in rates of burns and scalding. More high-quality research studies are needed in this area, therefore, to support the continued use of the community approach.

10.1002/14651858.CD004335.pub2

cochrane-simplification-train-2559

cochrane-simplification-train-2559

We included six trials with 498 participants with TS, 267 participants were randomised to oxandrolone plus GH treatment and 231 participants were randomised to GH only treatment. The individual trial sample size ranged between 22 and 133 participants. The included trials were conducted in 65 different paediatric endocrinology healthcare facilities including clinics, centres, hospitals and academia in the USA and Europe. The duration of interventions ranged between 3 and 7.6 years. The mean age of participants at start of therapy ranged from 9 to 12 years. Overall, we judged only one trial at low risk of bias in all domains and another trial at high risk of bias in most domains. We downgraded the level of evidence mainly because of imprecision (low number of trials, low number of participants or both). Comparing oxandrolone plus GH with GH only for final adult height showed a mean difference (MD) of 2.7 cm in favour of oxandrolone plus GH treatment (95% confidence interval (CI) 1.3 to 4.1; P < 0.001; 5 trials, 270 participants; moderate-quality evidence). The 95% prediction interval ranged between 0.3 cm and 5.1 cm. For adverse events, we based our main analysis on reliable date from two trials with overall low risk of bias. There was no evidence of a difference between oxandrolone plus GH and GH for adverse events (RR 1.81, 95% CI 0.83 to 3.96; P = 0.14; 2 trials, 170 participants; low-quality evidence). Six out of 86 (18.6%) participants receiving oxandrolone plus GH compared with 8/84 (9.5%) participants receiving GH only reported adverse events, mainly signs of virilisation (e.g. deepening of the voice). One trial each investigated the effects of treatments on speech (voice frequency; 88 participants), cognition (51 participants) and psychological status (106 participants). The overall results for these comparisons were inconclusive (very low-quality evidence). No trial reported on health-related quality of life or all-cause mortality. Addition of oxandrolone to the GH therapy led to a modest increase in the final adult height of girls aged up to 18 years with TS. Adverse effects identified included virilising effects such as deepening of the voice, but reporting was inadequate in some trials.

We included six randomised controlled trials (clinical trials where people are randomly put into one of two or more treatment groups). The duration of the treatments ranged between 3 and 7.6 years. Study authors allocated 498 participants to treatment groups, 267 participants to oxandrolone plus growth hormone treatment and 231 participants to growth hormone only treatment. The average age of the children at begin of treatment ranged from 9 to 12 years. This evidence is up to date as of October 2018. When comparing oxandrolone plus growth hormone to growth hormone only, the final adult height was on average 2.7 cm higher in favour of oxandrolone plus growth hormone therapy. Only two studies provided reliable data on side effects: 6 out of 86 (19%) participants given oxandrolone plus growth hormone compared with 8 out of 84 (10%) participants given growth hormone only reported side effects, mainly signs of development of male physical characteristics (for example deepening of the voice). One study investigated the effects of treatments on speech, the process of acquiring knowledge and understanding (cognition), and mental and emotional (psychological) status. The overall results for these were inconclusive. No trial measured people's satisfaction with their life and health or death from any cause. For side effects and effects on speech, cognition and psychological status, we are uncertain or very uncertain, mainly because the number of studies and participants was low and results were vague. For final adult height, we think that further research is likely to have an important impact on our confidence in the results and may change the results.

10.1002/14651858.CD010736.pub2

cochrane-simplification-train-2560

cochrane-simplification-train-2560

Twenty-seven studies involving 11,398 participants met the eligibility and study quality criteria for inclusion. Twenty studies compared stand alone clinical pathways with usual care. These studies indicated a reduction in in-hospital complications (odds ratio (OR) 0.58; 95% confidence interval (CI) 0.36 to 0.94) and improved documentation (OR 11.95: 95%CI 4.72 to 30.30). There was no evidence of differences in readmission to hospital or in-hospital mortality. Length of stay was the most commonly employed outcome measure with most studies reporting significant reductions. A decrease in hospital costs/ charges was also observed, ranging from WMD +261 US$ favouring usual care to WMD -4919 US$ favouring clinical pathways (in US$ dollar standardized to the year 2000). Considerable heterogeneity prevented meta-analysis of length of stay and hospital cost results.  An assessment of whether lower hospital costs contributed to cost shifting to another health sector was not undertaken. Seven studies compared clinical pathways as part of a multifaceted intervention with usual care. No evidence of differences were found between intervention and control groups. Clinical pathways are associated with reduced in-hospital complications and improved documentation without negatively impacting on length of stay and hospital costs.

Twenty-seven studies involving 11,398 participants were included for analysis. The main results were a reduction in in-hospital complications and improved documentation associated with clinical pathways. Complications assessed included wound infections, bleeding and pneumonia. Most studies reported a decreased length of stay and reduction in hospital costs when clinical pathways were implemented. Considerable variation in study design and settings prevented statistical pooling of results for length of stay and hospital costs. Generally poor reporting prevented the identification of characteristics common to successful clinical pathways. The authors concluded that clinical pathways are associated with reduced in-hospital complications

10.1002/14651858.CD006632.pub2

cochrane-simplification-train-2561

cochrane-simplification-train-2561

We included 40 publications, describing seven unique RCT's. The follow-up of the studies was 24 months, with only one extended to five years. Five studies had a low risk of bias, although there is a risk of bias in the included studies due to sponsoring and absence of any kind of blinding. One study compared disc replacement against rehabilitation and found a statistically significant advantage in favour of surgery, which, however, did not reach the predefined threshold for clinical relevance. Six studies compared disc replacement against fusion and found that the mean improvement in VAS back pain was 5.2 mm (of 100 mm) higher (two studies, 676 patients; 95% confidence interval (CI) 0.18 to 10.26) with a low quality of evidence while from the same studies leg pain showed no difference. The improvement of Oswestry score at 24 months in the disc replacement group was 4.27 points more than in the fusion group (five studies; 1207 patients; 95% CI 1.85 to 6.68) with a low quality of evidence. Both upper bounds of the confidence intervals for VAS back pain and Oswestry score were below the predefined clinically relevant difference. Choice of control group (circumferential or anterior fusion) did not appear to result in different outcomes. Although statistically significant, the differences between disc replacement and conventional fusion surgery for degenerative disc disease were not beyond the generally accepted clinical important differences with respect to short-term pain relief, disability and Quality of Life. Moreover, these analyses only represent a highly selected population. The primary goal of prevention of adjacent level disease and facet joint degeneration by using total disc replacement, as noted by the manufacturers and distributors, was not properly assessed and not a research question at all. Unfortunately, evidence from observational studies could not be used because of the high risk of bias, while these could have improved external validity assessment of complications in less selected patient groups. Non-randomised studies should however be very clear about patient selection and should incorporate independent, blinded outcome assessment, which was not the case in the excluded studies. Therefore, because we believe that harm and complications may occur after years, we believe that the spine surgery community should be prudent about adopting this technology on a large scale, despite the fact that total disc replacement seems to be effective in treating low-back pain in selected patients, and in the short term is at least equivalent to fusion surgery.

We identified seven randomised trials—involving a total of 1474 patients. Only one study compared total disc replacement with nonsurgical treatment, suggesting that surgery resulted in slightly better outcomes than intensive rehabilitation. But this did not translate into a clinically significant advantage that would make a major difference in patients’ lives. Six randomised trials compared disc replacement with spinal fusion surgery. Most of these studies had a high potential for bias, raising the possibility that they might not have provided a fair test of the treatments under study. These trials found that patients who underwent total disc replacement had slightly better outcomes in terms of back pain and function than those who had fusion surgery. But again the differences did not appear clinically significant. The review could not find evidence of any other benefits of total disc replacement, and the studies provided no insights on the long-term risks associated with it. Given the gaps in the evidence, the review concluded that the spine surgery community should be prudent about adopting this technology on a large scale.

10.1002/14651858.CD008326.pub2

cochrane-simplification-train-2562

cochrane-simplification-train-2562

For the original Cochrane Review, the review authors identified two RCTs involving 54 participants with ALS receiving NIV. There were no new RCTs or quasi-RCTs at the first update. One new RCT was identified in the second update but was excluded for the reasons outlined below. Incomplete data were available for one published study comparing early and late initiation of NIV (13 participants). We contacted the trial authors, who were not able to provide the missing data. The conclusions of the review were therefore based on a single study of 41 participants comparing NIV with standard care. Lack of (or uncertain) blinding represented a risk of bias for participant- and clinician-assessed outcomes such as quality of life, but it was otherwise a well-conducted study with a low risk of bias. The study provided moderate-quality evidence that overall median survival was significantly different between the group treated with NIV and the standard care group. The median survival in the NIV group was 48 days longer (219 days compared to 171 days for the standard care group (estimated 95% confidence interval 12 to 91 days, P = 0.0062)). This survival benefit was accompanied by an enhanced quality of life. On subgroup analysis, in the subgroup with normal to moderately impaired bulbar function (20 participants), median survival was 205 days longer (216 days in the NIV group versus 11 days in the standard care group, P = 0.0059), and quality of life measures were better than with standard care (low-quality evidence). In the participants with poor bulbar function (21 participants), NIV did not prolong survival or improve quality of life, although there was significant improvement in the mean symptoms domain of the Sleep Apnea Quality of Life Index by some measures. Neither trial reported clinical data on intervention-related adverse effects. Moderate-quality evidence from a single RCT of NIV in 41 participants suggests that it significantly prolongs survival, and low-quality evidence indicates that it improves or maintains quality of life in people with ALS. Survival and quality of life were significantly improved in the subgroup of people with better bulbar function, but not in those with severe bulbar impairment. Adverse effects related to NIV should be systematically reported, as at present there is little information on this subject. More RCT evidence to support the use of NIV in ALS will be difficult to generate, as not offering NIV to the control group is no longer ethically justifiable. Future studies should examine the benefits of early intervention with NIV and establish the most appropriate timing for initiating NIV in order to obtain its maximum benefit. The effect of adding cough augmentation techniques to NIV also needs to be investigated in an RCT. Future studies should examine the health economics of NIV. Access to NIV remains restricted in many parts of the world, including Europe and North America. We need to understand the factors, personal and socioeconomic, that determine access to NIV.

In this updated review, we examined the evidence from two randomised trials of NIV in ALS involving a total of 54 participants. One of the trials, which studied when to start NIV, provided no usable data. A third trial, identified in a clinical trials register, currently has no published results. Complete data were only available from a single trial of 41 participants. The results of this trial provided moderate-quality evidence that NIV significantly prolongs survival, and low-quality evidence that it improves or maintains quality of life compared to standard care. Median survival was increased by an estimated 48 days, from 171 to 219 days. The survival benefit from NIV was much greater in people with ALS in whom the muscles used for speaking, chewing, and swallowing (bulbar muscles) were either unaffected or only moderately weak. Among these 20 participants, the median survival with NIV was increased by an estimated 205 days (216 days with NIV, compared to 11 days with standard care). Quality of life was also maintained in participants with mild to moderate bulbar weakness. In the 21 participants with severe bulbar weakness, NIV did not prolong survival or maintain quality of life scores, although a sleep-related symptoms score improved. Neither trial reported on adverse effects. Participants and clinicians were aware of the treatment groups, which can influence quality of life assessments. More trials of NIV versus standard care in ALS are unlikely as it would not be ethical to withhold NIV. Future studies should examine early intervention with NIV and determine the best time to start it. The evidence is up to date to January 2017.

10.1002/14651858.CD004427.pub4

cochrane-simplification-train-2563

cochrane-simplification-train-2563

We included 41 studies involving 28,700 people. Nineteen new studies were identified in this update, adding to the 22 studies included in the previous two iterations of the review. Three studies measured informed decision with regard to the uptake of screening following personalised risk communication as a part of their intervention. All of these three studies were at low risk of bias and there was strong evidence that the interventions enhanced informed decision making, although with heterogeneous results. Overall 45.2% (592/1309) of participants who received personalised risk information made informed choices, compared to 20.2% (229/1135) of participants who received generic risk information. The overall odds ratios (ORs) for informed decision were 4.48 (95% confidence interval (CI) 3.62 to 5.53 for fixed effect) and 3.65 (95% CI 2.13 to 6.23 for random effects). Nine studies measured increase in knowledge, using different scales. All of these studies showed an increase in knowledge with personalised risk communication. In three studies the interventions showed a trend towards more accurate risk perception, but the evidence was of poor quality. Four out of six studies reported non-significant changes in anxiety following personalised risk communication to the participants. Overall there was a small non-significant decrease in the anxiety scores. Most studies (32/41) measured the uptake of screening tests following interventions. Our results (OR 1.15 (95% CI 1.02 to 1.29)) constitute low quality evidence, consistent with a small effect, that personalised risk communication in which a risk score was provided (6 studies) or the participants were given their categorised risk (6 studies), increases uptake of screening tests. There is strong evidence from three trials that personalised risk estimates incorporated within communication interventions for screening programmes enhance informed choices. However the evidence for increasing the uptake of such screening tests with similar interventions is weak, and it is not clear if this increase is associated with informed choices. Studies included a diverse range of screening programmes. Therefore, data from this review do not allow us to draw conclusions about the best interventions to deliver personalised risk communication for enhancing informed decisions. The results are dominated by findings from the topic area of mammography and colorectal cancer. Caution is therefore required in generalising from these results, and particularly for clinical topics other than mammography and colorectal cancer screening.

In this review we looked at studies that provided personalised risk information for each participant, so that he or she could make a decision about whether to undergo screening, based on their personal risk profile. We found 41 studies with 28,700 participants that provided such personalised risk information to the participants. We integrated the results of all these studies and found that when such a risk profile was included in the intervention, the participants made more informed decisions about screening, compared to people who were provided with more general risk information. Overall 45.2% (592/1309) of participants who received personalised risk information made informed choices as compared to 20.2% (229/1135) of participants who received generic risk information. We also found that these interventions seemed to increase knowledge and may increase accuracy of risk perception in the trial participants. However they did not significantly affect participants' anxiety. The results also indicated that providing people with personalised risks of the disease resulted in a small increase in the number of people who undertook the screening procedure. The results from this review are dominated by studies screening for breast cancer and colorectal cancer. Caution is required in applying these results to other types of screening.

10.1002/14651858.CD001865.pub3

cochrane-simplification-train-2564

cochrane-simplification-train-2564

We included data from two studies (619 eyes of 401 participants) that compared FA implants with standard-of-care therapy. Both studies used similar standard-of-care therapy that included administration of prednisolone and, if needed, immunosuppressive agents. The studies included participants from Australia, France, Germany, Israel, Italy, Portugal, Saudi Arabia, Spain, Switzerland, Turkey, the United Kingdom, and the United States. We assessed both studies at high risk of performance and detection bias. Only one study reported our primary outcome, recurrence of uveitis at any point during the study through 24 months. The evidence, judged as moderate-quality, showed that a FA implant probably prevents recurrence of uveitis compared with standard-of-care therapy (risk ratio (RR) 0.29, 95% confidence interval (CI) 0.14 to 0.59; 132 eyes). Both studies reported safety outcomes, and moderate-quality evidence showed increased risks of needing cataract surgery (RR 2.98, 95% CI 2.33 to 3.79; 371 eyes) and surgery to lower intraocular pressure (RR 7.48, 95% CI 3.94 to 14.19; 599 eyes) in the implant group compared with standard-of-care therapy through two years of follow-up. No studies compared dexamethasone implants with standard-of-care therapy. After considering both benefits and harms reported from two studies in which corticosteroids implants were compared with standard-of-care therapy, we are unable to conclude that the implants are superior to traditional systemic therapy for the treatment of non-infectious uveitis. These studies exhibited heterogeneity in design and outcomes that measured efficacy. Pooled findings regarding safety outcomes suggest increased risks of post-implant surgery for cataract and high intraocular pressure compared with standard-of-care therapy.

We included two randomized controlled trials that compared fluocinolone acetonide implants with standard-of-care therapy. These studies included 401 participants from Australia, France, Germany, Israel, Italy, Portugal, Saudi Arabia, Spain, Switzerland, Turkey, the United Kingdom, and the United States who were 6 years old or older and were followed for two years. The evidence is current to 6 November 2015. Since the two studies were designed to answer slightly different questions about the fluocinolone implant, we were not able to combine data from both studies to compare how well the medications worked. However, we were able to do a combined analysis of the common side effects, which suggest that participants in the steroid implant group had more surgery for cataract (clouding of the lens of the eye) and for high eye pressure than participants in the non-implant group. We were unable to determine whether the steroid implants were better than standard-of-care therapy. The overall quality of the presently available published evidence was moderate. This finding indicates that future published research is likely to have an important impact on the conclusions currently provided in this review.

10.1002/14651858.CD010469.pub2

cochrane-simplification-train-2565

cochrane-simplification-train-2565

We included four studies with 1029 participants. All the studies used a parallel-group design, and included an initial titration phase to determine the maximum effective and tolerated dose, followed by a maintenance phase. Tapentadol medication was taken twice daily and doses ranged from 50 to 500 mg per day. Rescue medication (morphine or oxycodone immediate-release) was available to participants in all studies. Overall, 440 participants were randomised in classically designed RCTs, and 589 participants were enrolled in enriched-enrolment, randomised-withdrawal (EERW) trials. A total of 476 participants were randomised to titration with tapentadol and 338 participants took tapentadol throughout the maintenance phase of their trial. All studies used numerical rating scores, Patient Global Impression of Change scores, and use of rescue medication as measures of efficacy, and all reported on adverse events and withdrawals. All studies enrolled fewer than 200 participants per treatment arm and were therefore at risk of overestimating efficacy. One study was terminated early due to problems with supply of rescue medication, with fewer than 20 participants enrolled per treatment arm in the maintenance phase of the trial. We judged another study at high risk of bias due to an open-label design. There were insufficient data for pooling and statistical analysis. Response rates for pain intensity were comparable across treatment groups in each study. In one EERW study, response rates were high across both treatment and placebo arms during the maintenance phase (62% tapentadol, 69% morphine, 50% placebo). For pain relief, tapentadol is no more and no less effective than oxycodone or morphine (low quality evidence). Treatment emergent adverse event rates were high, approximately 50% to 90%. The most common adverse events were gastrointestinal (nausea, vomiting, constipation) (low quality evidence). There was no advantage of tapentadol over morphine or oxycodone in terms of serious adverse events. The number of people experiencing effects on consciousness, appetite, or thirst was low. Information from RCTs on the effectiveness and tolerability of tapentadol was limited. The available studies were of moderate or small size and used different designs, which prevented pooling of data. Pain relief and adverse events were comparable between the tapentadol and morphine and oxycodone groups.

We found four studies with 1029 participants. All four studies compared participants taking tapentadol to participants taking similar medicine, such as morphine or oxycodone. All studies gave participants a period of time to find the best dose to take, before continuing on the medication and comparing their pain levels. All the studies were small or medium sized, so the results are at risk of being influenced by random fluctuations rather than real differences, and they may also overestimate any effects. One trial allowed participants to know what medication they were taking, and one trial was stopped early due administrative problems, so they did not have enough people in the study. We have to be cautious interpreting results from these studies. Because the studies all used different designs, we could not compare the results from one with another. However, each study showed that there was not much difference between the pain levels of people taking tapentadol and people taking morphine and oxycodone. Pain levels were generally well controlled. The studies also showed there was no measurable difference in how many adverse effects people had while taking tapentadol, morphine, or oxycodone. Therefore, we can conclude only that the studies to date show tapentadol was no more or less effective and no more or less well tolerated than morphine and oxycodone.

10.1002/14651858.CD011460.pub2

cochrane-simplification-train-2566

cochrane-simplification-train-2566

We include 31 studies (32 comparisons) randomising 1651 preterm infants. Literature searches in 2018 identified one new study for inclusion. No new on-going trials were identified and no studies used darbepoetin. Most included trials were of small sample size. The meta-analysis showed a significant effect on the use of one or more RBC transfusions (21 studies (n = 1202); typical risk ratio (RR) 0.72, 95% confidence interval (CI) 0.65 to 0.79; typical risk difference (RD) -0.17, 95% CI -0.22 to -0.12; typical number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 5 to 8). There was moderate heterogeneity for this outcome (RR I² = 66%; RD I² = 58%). The quality of the evidence was very low. We obtained similar results in secondary analyses based on different combinations of high/low doses of EPO and iron supplementation. There was no significant reduction in the total volume (mL/kg) of blood transfused per infant (typical mean difference (MD) -1.6 mL/kg, 95% CI -5.8 to 2.6); 5 studies, 197 infants). There was high heterogeneity for this outcome (I² = 92%). There was a significant reduction in the number of transfusions per infant (11 studies enrolling 817 infants; typical MD -0.22, 95% CI -0.38 to -0.06). There was high heterogeneity for this outcome (I² = 94%). Three studies including 404 infants reported on retinopathy of prematurity (ROP) (all stages or stage not reported), with a typical RR 1.27 (95% CI 0.99 to 1.64) and a typical RD of 0.09 (95% CI -0.00 to 0.18). There was high heterogeneity for this outcome for both RR (I² = 83%) and RD (I² = 82%). The quality of the evidence was very low.Three trials enrolling 442 infants reported on ROP (stage ≥ 3). The typical RR was 1.73 (95% CI 0.92 to 3.24) and the typical RD was 0.05 (95% CI -0.01 to 0.10). There was no heterogeneity for this outcome for RR (I² = 18%) but high heterogeneity for RD (I² = 79%). The quality of the evidence was very low.There were no significant differences in other clinical outcomes including mortality and necrotising enterocolitis. For the outcomes of mortality and necrotising enterocolitis, the quality of the evidence was moderate. Long-term neurodevelopmental outcomes were not reported. Late administration of EPO reduces the use of one or more RBC transfusions, the number of RBC transfusions per infant (< 1 transfusion per infant) but not the total volume (mL/kg) of RBCs transfused per infant. Any donor exposure is likely not avoided as most studies included infants who had received RBC transfusions prior to trial entry. Late EPO does not significantly reduce or increase any clinically important adverse outcomes except for a trend in increased risk for ROP. Further research of the use of late EPO treatment, to prevent donor exposure, is not indicated. Research efforts should focus on limiting donor exposure during the first few days of life in sick neonates, when RBC requirements are most likely to be required and cannot be prevented by late EPO treatment. The use of satellite packs (dividing one unit of donor blood into many smaller aliquots) may reduce donor exposure.

To date, 1651 infants (between eight and 28 days of age) born preterm have been enrolled in 31 studies of late administration of EPO to reduce the use of red blood cell transfusions and to prevent donor exposure. There were no studies that used darbepoetin. We have not received any funding for this review and we have no conflicts of interest to declare. The risk of receiving red blood transfusion is reduced following initiation of EPO treatment. However, the overall benefit of EPO is reduced as many of these infants had been exposed to donor blood prior to entry into the trials. Treatment with late EPO did not have any important effects on death or common complications of preterm birth, except for trends towards an increased risk for retinopathy of prematurity. Retinopathy of prematurity is a disease of the eye affecting infants born preterm. It is thought to be caused by disorganised growth of retinal blood vessels, which may result in scarring and retinal detachment. Retinopathy of prematurity can be mild and may resolve spontaneously, but it may lead to blindness in serious cases. The study quality varied and important information regarding the random sequence generation and whether the allocation was concealed or not was often missing. Sample sizes were small and long-term outcomes (18 to 24 months of corrected age) were not reported. The quality of the evidence was very low for the outcomes of "use of one or more red blood cell transfusions," "retinopathy of prematurity (all stages or stage not reported)" and for "retinopathy of prematurity (stage ≥ 3)". For the outcomes of "necrotising enterocolitis" and "mortality", the quality of the evidence was moderate.

10.1002/14651858.CD004868.pub6

cochrane-simplification-train-2567

cochrane-simplification-train-2567

The updated searches identified one additional published study, and one clinical trial registry report. We included five studies reporting on 687 participants; 637 had painful diabetic neuropathy and 50 had postherpetic neuralgia. Two studies used a cross-over design and three used a parallel group design; all studies used a placebo comparator, although one study used an active placebo (benztropine). Modified-release oxycodone (oxycodone MR) was titrated to effect and tolerability. One study used a fixed dose combination of oxycodone MR and naloxone. Two studies added oxycodone therapy to ongoing, stable treatment with either pregabalin or gabapentin. All studies had one or more sources of potential major bias. No study reported the proportion of participants experiencing 'substantial benefit' (at least 50% pain relief or who were very much improved). Three studies (537 participants) in painful diabetic neuropathy reported outcomes equivalent to 'moderate benefit' (at least 30% pain relief or who were much or very much improved), which was experienced by 44% of participants with oxycodone and 27% with placebo (number needed to treat for one additional beneficial outcome (NNT) 5.7). All studies reported group mean pain scores at the end of treatment. Three studies reported a greater pain intensity reduction and better patient satisfaction with oxycodone MR alone than with placebo. There was a similar result in the study adding oxycodone MR to stable, ongoing gabapentin, but adding oxycodone MR plus naloxone to stable, ongoing pregabalin did not show any additional effect. More participants experienced adverse events with oxycodone MR alone (86%) than with placebo (63%); the number needed to treat for an additional harmful outcome (NNH) was 4.3. Serious adverse events (oxycodone 3.4%, placebo 7.0%) and adverse event withdrawals (oxycodone 11%, placebo 6.4%) were not significantly different between groups. Withdrawals due to lack of efficacy were less frequent with oxycodone MR (1.1%) than placebo (11%), with a number needed to treat to prevent one withdrawal of 10. The add-on studies reported similar results. We downgraded the quality of the evidence to very low for all outcomes, due to limitations in the study methods, heterogeneity in the pain condition and study methods, and sparse data. There was only very low quality evidence that oxycodone (as oxycodone MR) is of value in the treatment of painful diabetic neuropathy or postherpetic neuralgia. There was no evidence for other neuropathic pain conditions. Adverse events typical of opioids appeared to be common.

In December 2015, we updated searches from an earlier Cochrane review to look for clinical trials that used oxycodone to treat neuropathic pain in adults. We found two additional studies to include. The earlier review included three studies that compared oxycodone with placebo over several weeks, and the additional studies added oxycodone to existing treatment with pregabalin or gabapentin. Most of the 687 people in the studies had painful limbs because of damaged nerves caused by diabetes. Only very low quality evidence suggested that oxycodone relieved the pain. Compared with placebo, fewer people stopped taking oxycodone because they felt it was not effective, but more people experienced side effects. We rated the quality of the evidence for both benefit and harm as very low because of small numbers of studies and participants, the outcomes reported, and potential bias from the way the studies were analysed. Very low quality evidence means that we are very uncertain about the results.

10.1002/14651858.CD010692.pub3

cochrane-simplification-train-2568

cochrane-simplification-train-2568

We identified four trials involving 1314 children. Three trials investigated the use of amoxicillin/clavulanic acid to prevent otitis and one investigated ampicillin to prevent pneumonia. The use of amoxicillin/clavulanic acid compared to placebo to prevent otitis showed a risk ratio (RR) of 0.70 (95% confidence interval (CI) 0.45 to 1.11, three trials, 414 selected children, moderate-quality evidence). Methods of random sequence generation and allocation concealment were not clearly stated in two trials. Performance, detection and reporting bias could not be ruled out in three trials. Ampicillin compared to supportive care (continuation of breastfeeding, clearing of the nose and paracetamol for fever control) to prevent pneumonia showed a RR of 1.05 (95% CI 0.74 to 1.49, one trial, 889 selected children, moderate-quality evidence). The trial was non-blinded. Random sequence generation and allocation concealment methods were not clearly stated, so the possibility of reporting bias could not be ruled out. Harm outcomes could not be analysed as they were expressed only in percentages. We found no studies assessing mastoiditis, quinsy, abscess, meningitis, hospital admission or death. There is insufficient evidence for antibiotic use as a means of reducing the risk of otitis or pneumonia in children up to five years of age with undifferentiated ARIs. Further high-quality research is needed to provide more definitive evidence of the effectiveness of antibiotics in this population.

In the trials treating otitis media, the quality of the evidence was moderate as the methods for avoiding bias were not clearly stated. Furthermore, in one trial a pharmaceutical company prepared the placebo syrup used in the trial. In the study treating pneumonia, we classified the quality of the evidence as moderate, because the families previously knew if their children were receiving antibiotics or not. Furthermore, the methods for avoiding bias were not clearly stated by the trial authors. Further high-quality research is needed to provide more definitive evidence of the effectiveness of antibiotics in this population.

10.1002/14651858.CD007880.pub3

cochrane-simplification-train-2569

cochrane-simplification-train-2569

We included 20 RCTs with 1574 participants in this updated review. All trials were published in Chinese language journals. We included 14 trials that we had excluded in the previous version of the review after we added a new outcome in this update. Time windows within which the participants were randomised ranged from 4.5 hours to 10 days. Ischaemic stroke was confirmed by computerised tomography (CT) or magnetic resonance imaging (MRI) in 18 trials. Meta-analysis of two trials with 164 participants showed that treatment with puerarin did not reduce death or dependency at final follow-up (RR 0.79, 95% CI 0.45 to 1.36). One trial with 83 participants reported that the mean value of the Barthel Index in the puerarin group was below that in the control group. Meta-analysis of 16 trials with 1305 participants showed that puerarin reduced the proportion of participants without improvement of neurological deficit at the end of follow-up (RR 0.42, 95% CI 0.33 to 0.55). None of the included trials reported serious adverse effects.The quality of evidence was low due to incomplete reporting of the methods and short-term follow-up. There is not enough evidence to evaluate the effect of puerarin on survival or dependency in people with ischaemic stroke. High quality and large-scale RCTs with long-term follow-up are needed to assess its efficacy.

We searched for trials up to August 2015 and included 20 randomised controlled trials involving 1574 participants, of puerarin for people with ischaemic stroke. Only two trials reported death or dependency at the end of follow-up. The remaining studies followed participants for less than one month. We included 20 RCTs with 1574 participants in this updated review; five trials were new. Treatment with puerarin did not reduce death or dependency at final follow-up. Puerain improved neurological deficit at the end of treatment. The included trials did not report serious adverse effects. The quality of evidence was low due to incomplete reporting of the methods and short-term follow-up.

10.1002/14651858.CD004955.pub3

cochrane-simplification-train-2570

cochrane-simplification-train-2570

Three trials randomly allocating people with age-related cataract to MSICS or ECCE were included in this review (n = 953 participants). Two trials were conducted in India and one in Nepal. Trial methods, such as random allocation and allocation concealment, were not clearly described; in only one trial was an effort made to mask outcome assessors. The three studies reported follow-up six to eight weeks after surgery. In two studies, more participants in the MSICS groups achieved unaided visual acuity of 6/12 or 6/18 or better compared to the ECCE group, but overall not more than 50% of people achieved good functional vision in the two studies. 10/806 (1.2%) of people enrolled in two trials had a poor outcome after surgery (best-corrected vision less than 6/60) with no evidence of difference in risk between the two techniques (risk ratio (RR) 1.58, 95% confidence interval (CI) 0.45 to 5.55). Surgically induced astigmatism was more common with the ECCE procedure than MSICS in the two trials that reported this outcome. In one study there were more intra- and postoperative complications in the MSICS group. One study reported that the costs of the two procedures were similar. There are no other studies from other countries other than India and Nepal and there are insufficient data on cost-effectiveness of each procedure. Better evidence is needed before any change may be implemented. Future studies need to have longer-term follow-up and be conducted to minimize biases revealed in this review with a larger sample size to allow examination of adverse events.

We found three randomised controlled trials. The searches are up to date to September 23rd 2014. A total of 953 people with age-related cataract in India and Nepal were randomly allocated to MSICS and ECCE in these trials. The data were limited. People whose lens was removed with MSICS were more likely to achieve good functional vision, however, overall not more than 50% of people achieved good functional vision in the two studies. 1.2% of people enrolled in two trials had a poor outcome after surgery with best-corrected vision less than 6/60. There was no evidence of any difference between the two groups with respect to this outcome. Surgically induced astigmatism was more common with the ECCE procedure than MSICS in the two trials that reported this outcome. In one study there were more intra- and postoperative complications in the MSICS group. One study reported that the costs of the two procedures were similar. We judged the quality of the evidence to be low or very low. There were only three studies and we could not combine the data because of differences in reporting and inconsistency between trials which meant that some of the results were imprecise.

10.1002/14651858.CD008811.pub3

cochrane-simplification-train-2571

cochrane-simplification-train-2571

Three randomised clinical trials (307 patients) that followed patients for three months or more after the end of treatment were included. The methodological quality was poor. The herbal compound 'Jianpi Wenshen recipe' had significant effects on viral markers compared to interferon: relative risk 2.40 (95% CI 1.01 to 5.72) for clearance of serum HBsAg, 2.03 (95% CI 0.98 to 4.20) for clearance of HBeAg, and 2.54 (95% CI 1.13 to 5.70) for seroconversion of HBeAg to anti-HBe. Phyllanthus amarus and Astragalus membranaceus showed no significant antiviral effect compared with placebo. Analysis of pooling eight randomised clinical trials with less than three months follow-up did not show a significant benefit of Chinese medicinal herbs on viral markers. Data on long-term clinical outcomes and quality of life were lacking. Based on one low quality trial, the medicinal herb 'Jianpi Wenshen recipe' may have an antiviral activity in asymptomatic carriers of hepatitis B virus. However, rigorous randomised, double-blind, placebo-controlled trials are needed before herbs should be used for this condition.

Three randomised clinical trials were included. Due to their poor methodologic quality and the existing small number of trials, there is currently insufficient evidence for treating asymptomatic hepatitis B virus carriers with Chinese medicinal herbs like the herbal compound 'Jianpi Wenshen recipe', Phyllanthus amarus and Astragalus membranaceus. Methodologically better and larger randomised trials are needed comparing medicinal herbs versus placebo.

10.1002/14651858.CD002231

cochrane-simplification-train-2572

cochrane-simplification-train-2572

We included eight studies evaluating the effectiveness of different interventions designed to support the uptake of systematic review evidence. The overall quality of the evidence was very low to moderate. Two cluster RCTs evaluated the effectiveness of multifaceted interventions, which contained access to systematic reviews relevant to reproductive health, to change obstetric care; the high baseline performance in some of the key clinical indicators limited the findings of these studies. There were no statistically significant effects on clinical practice for all but one of the clinical indicators in selected obstetric units in Thailand (median effect size 4.2%, range -11.2% to 18.2%) and none in Mexico (median effect size 3.5%, range 0.1% to 19.0%). In the second cluster RCT there were no statistically significant differences in selected obstetric units in the UK (median effect RR 0.92; range RR 0.57 to RR 1.10). One RCT evaluated the perceived understanding and ease of use of summary of findings tables in Cochrane Reviews. The median effect of the differences in responses for the acceptability of including summary of findings tables in Cochrane Reviews versus not including them was 16%, range 1% to 28%. One RCT evaluated the effect of an analgesic league table, derived from systematic review evidence, and there was no statistically significant effect on self-reported pain. Only one RCT evaluated an organisational intervention (which included a knowledge broker, access to a repository of systematic reviews and provision of tailored messages), and reported no statistically significant difference in evidence informed programme planning. Three interrupted time series studies evaluated the dissemination of printed bulletins based on evidence from systematic reviews. A statistically significant reduction in the rates of surgery for glue ear in children under 10 years (mean annual decline of -10.1%; 95% CI -7.9 to -12.3) and in children under 15 years (quarterly reduction -0.044; 95% CI -0.080 to -0.011) was reported. The distribution to general practitioners of a bulletin on the treatment of depression was associated with a statistically significant lower prescribing rate each quarter than that predicted by the rates of prescribing observed before the distribution of the bulletin (8.2%; P = 0.005). Mass mailing a printed bulletin which summarises systematic review evidence may improve evidence-based practice when there is a single clear message, if the change is relatively simple to accomplish, and there is a growing awareness by users of the evidence that a change in practice is required. If the intention is to develop awareness and knowledge of systematic review evidence, and the skills for implementing this evidence, a multifaceted intervention that addresses each of these aims may be required, though there is insufficient evidence to support this approach.

Systematic reviews can help with this process by bringing together the relevant evidence and using clear methods which seek to minimise bias. Interventions to help improve the uptake of systematic review evidence have been developed to help with improving the use of evidence. We identified eight studies which evaluated the effectiveness of these types of interventions. There was some evidence to show that a clear message, based on systematic review evidence, which is targeted and disseminated to the relevant healthcare professionals may improve evidence-based practice. If the aim is to help decision-makers increase their awareness and knowledge of systematic review evidence, and evidence-based practice, then interventions that address some of these aims have been evaluated but have shown little effect on practice.

10.1002/14651858.CD009401.pub2

cochrane-simplification-train-2573

cochrane-simplification-train-2573

We included 12 studies (430 participants) in the review: seven RCTs and five CCTs where it was not clear whether participants were randomly allocated to groups. We did not include any unpublished studies. Participants included children and adults of both sexes. Only one study included pregnant women. All studies were conducted in high-income countries. The quality of the 11 studies in the initial meta-analysis was moderate, although we classified no study as having a low risk of bias on all criteria. We included 11 studies in the initial meta-analysis of gamma-globulin (concentrated polyclonal immunoglobulins) versus control (saline or no treatment) for rubella cases. The result favoured the intervention group (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.45 to 0.83) but was heterogenous (Chi² test = 36.59, df = 10 (P value < 0.0001); I² statistic = 73%). Heterogeneity was explained by subgrouping studies according to the estimated volume of gamma-globulin administered per pound of bodyweight and then removing those studies where the intervention was administered more than five days after participant exposure to rubella (post hoc analysis). The test of subgroup differences demonstrated heterogeneity between subgroups according to our protocol definition (P value < 0.1; I² statistic > 60%) and there appeared to be greater effectiveness of the intervention when a greater volume of gamma-globulin was administered ('0.027 to 0.037 ml/lb' RR 1.60 (95% CI 0.57 to 4.52); '0.1 to 0.15 ml/lb' RR 0.53 (95% CI 0.29 to 0.99); '0.2 to 0.5 ml/lb' RR 0.20 (95% CI 0.04 to 1.00)). None of the studies reported the outcome 'congenital rubella infection'. One included study reported on congenital rubella syndrome, with no cases among participants who were fewer than nine weeks pregnant at enrolment and who were randomised to one of two gamma-globulin groups ('high' or 'low' rubella titre). However, the study did not report how congenital rubella syndrome was measured and did not report the length of follow-up according to intervention group. This study did not include a non-treatment group. No included study measured adverse events. Compared to no treatment, polyclonal immunoglobulins seem to be of benefit for preventing rubella. The available evidence suggests that this intervention may be of benefit up to five days after exposure, and that effectiveness is dependent on dose. Considering the attack rate for rubella cases in the control group of the highest volume gamma-globulin subgroup (333 per 1000), the absolute risk reduction (calculated from the RR) for this volume of gamma-globulin was 266 (95% CI 0 to 320) and the number needed to treat to benefit is four (95% CI 3 to incalculable). The included studies did not measure rubella-specific antibodies in the immunoglobulin products used in a standard way and thus estimation of the dose of rubella-specific antibodies in international units administered was not possible. As the concentration of rubella-specific antibodies in today's polyclonal immunoglobulin products may vary from those products used in the studies in the review, the volume required per pound of bodyweight to produce similar results may also vary. There is insufficient evidence to make direct conclusions about the effectiveness of polyclonal immunoglobulins for preventing congenital rubella syndrome. This is an area requiring further research.

The evidence is current to August 2014. We included 12 studies (430 participants). People of all ages were included in the studies, which were conducted in high-income countries. Eleven studies (389 participants) compared injecting antibodies into the muscle or vein of participants to injecting salt water or giving no treatment. The study participants did not have their own antibodies. They had been in contact with rubella between one and 28 days prior to receiving the antibodies. The antibodies seemed to be effective at preventing participants from catching rubella, with those receiving antibodies 39% less likely to develop rubella than those not given antibodies. In an analysis of the seven studies (89 participants) where participants had been in contact with rubella only up to five days earlier, people given the highest doses used in the studies were 80% less likely to develop rubella than those not given antibodies. The studies assessing the prevention of rubella were of moderate quality because of some methodological issues and the fairly small number of participants. It is important to consider that the amount of rubella antibodies in today's blood donations may differ from those used in the studies. Therefore, doses given today may need to vary from those of the studies in order to obtain the same effect. Only one study included pregnant women. All of the women were given one of two different doses of antibodies. They did not measure whether the babies born to the women were infected with rubella, but did consider whether birth defects that may be related to rubella were present. Key details about the study methods were missing and unobtainable, so the quality of this study was unclear. None of the babies born to these women were identified as having birth defects related to rubella. However, we cannot draw direct conclusions from this single study about the effectiveness of injecting antibodies after contact with rubella for preventing rubella-related birth defects in pregnant women. This is an area that needs further research. The included studies did not report adverse events. Future studies should report this outcome.

10.1002/14651858.CD010586.pub2

cochrane-simplification-train-2574

cochrane-simplification-train-2574

We included nine RCTs, that involved 2633 people with STEMI and multi-vessel coronary disease randomly assigned to either a complete (n = 1381) versus culprit-only (n = 1252) revascularisation strategy. The complete and the culprit-only revascularisation strategies did not differ for long-term all-cause mortality (65/1274 (5.1%) in complete group versus 72/1143 (6.3%) in culprit-only group; RR 0.80, 95% CI 0.58 to 1.11; participants = 2417; studies = 8; I2 = 0%; very low quality evidence). Compared with culprit-only intervention, the complete revascularisation strategy was associated with a lower proportion of long-term cardiovascular mortality (28/1143 (2.4%) in complete group versus 51/1086 (4.7%) in culprit-only group; RR 0.50, 95% CI 0.32 to 0.79; participants = 2229; studies = 6; I2 = 0%; very low quality evidence) and long-term non-fatal myocardial infarction (47/1095 (4.3%) in complete group versus 70/1004 (7.0%) in culprit-only group; RR 0.62, 95% CI 0.44 to 0.89; participants = 2099; studies = 6; I2 = 0%; very low quality evidence). The complete and the culprit-only revascularisation strategies did not differ in combined adverse events (51/2096 (2.4%) in complete group versus 57/1990 (2.9%) in culprit-only group; RR 0.84, 95% CI 0.58 to 1.21; participants = 4086; I2 = 0%; very low quality evidence). Complete revascularisation was associated with lower proportion of long-term revascularisation (145/1374 (10.6%) in complete group versus 258/1242 (20.8%) in culprit-only group; RR 0.47, 95% CI 0.39 to 0.57; participants = 2616; studies = 9; I2 = 31%; very low quality evidence). TSA of long-term all-cause mortality, long-term cardiovascular mortality, and long-term non-fatal myocardial infarction showed that more RCTs are needed to reach more conclusive results on these outcomes. Regarding long-term repeat revascularisation more RCTs may not change our present result. The quality of the evidence was judged to be very low for all primary and the majority of the secondary outcomes mainly due to risk of bias, imprecision, and indirectness. Compared with culprit-only intervention, the complete revascularisation strategy may be superior due to lower proportions of long-term cardiovascular mortality, long-term revascularisation, and long-term non-fatal myocardial infarction, but these findings are based on evidence of very low quality. TSA also supports the need for more RCTs in order to draw stronger conclusions regarding the effects of complete revascularisation on long-term all-cause mortality, long-term cardiovascular mortality, and long-term non-fatal myocardial infarction.

We searched for clinical trials in adults who had percutaneous coronary intervention for the management of heart attack and multi-vessel disease. The evidence is current to 4 January 2017. Only four trials reported funding from government organisations or charitable institutions. The other trials did not mention the source of funding and no private companies were mentioned as sources of finance. In the included trials, both the participants and researchers were aware of what treatment the participants received which may have biased the results. One trial ended enrolment earlier than planned because the difference between treatment was significant. This may have overestimated the difference between intervention groups. For most trials, the number of participants that were included was not enough to see a potential difference between treatments. We included nine clinical trials with 2633 people with heart attack and multi-vessel disease. Compared with participants who underwent opening of only the coronary artery that caused heart attack, people who underwent treatment on all narrowed vessels had fewer deaths from diseases of the heart and blood supply (called cardiovascular disease), required fewer treatments to open the problematic coronary arteries, and had fewer heart attacks at the end of one year or later since the treatment. Based on our analyses, although the treatment on all narrowed vessels appears to be a better treatment strategy, there still exists a need for more well-designed clinical trials to confirm that this approach is associated with fewer deaths from cardiovascular diseases or heart attack, or both. The evidence is of very low quality. For instance, the number of participants in the included studies was insufficient, the medical team was aware of the study group that the participants were allocated to and that may have affected our conclusions. There is a need for well-designed clinical trials with more participants to determine which treatment strategy is superior.

10.1002/14651858.CD011986.pub2

cochrane-simplification-train-2575

cochrane-simplification-train-2575

A single randomised controlled trial enrolling 92 participants was eligible for this review. Researchers have not reported long-term neurodevelopmental outcomes, including the primary outcome of this review - death or long-term major neurodevelopmental disability in infancy (18 months to three years of age). Cooling plus xenon was not associated with reduced mortality at latest follow-up, based upon low quality evidence. Investigators noted no substantial differences between groups for other secondary outcomes of this review, such as biomarkers of brain damage assessed with magnetic resonance imaging and occurrence of seizures during primary hospitalisation. Available data do not show an increased adverse event rate in the cooling plus xenon group compared with the cooling alone group. Current evidence from one small randomised controlled pilot trial is inadequate to show whether cooling plus xenon is safe or effective in near-term and term newborns with HIE. Further trials reporting long-term neurodevelopmental outcomes are needed.

This review found a single randomised controlled trial that examined the short-term effects of cooling plus xenon for infants with HIE. This trial enrolled 92 participants. Cooling plus xenon did not improve clinical outcomes before discharge from the hospital compared with cooling alone. Data on long-term development were not provided. Current low quality evidence is inadequate to show whether cooling plus xenon improves survival and development of newborn babies with HIE. Evidence is up-to-date as of August 2017.

10.1002/14651858.CD012753.pub2

cochrane-simplification-train-2576

cochrane-simplification-train-2576

We included 15 randomised clinical trials with 1034 participants randomised. All trials had a parallel group design. Nine trials were conducted in high-income countries and six trials in middle-income countries. All trials were at high risk of bias. Six trials included participants with chronic hepatitis C, four trials included participants with liver cirrhosis, four trials included participants with non-alcoholic fatty liver disease, and one trial included liver transplant recipients. All included trials reported the baseline vitamin D status of participants. Participants in six trials had baseline 25-hydroxyvitamin D levels at or above vitamin D adequacy (20 ng/mL), while participants in the remaining nine trials were vitamin D insufficient (less than 20 ng/mL). All trials administered vitamin D orally. Mean duration of vitamin D supplementation was 0.5 years and follow-up was 0.6 years. Eleven trials (831 participants; 40% women; mean age 52 years) tested vitamin D3, one trial (18 men; mean age 61 years) with three intervention groups tested vitamin D2 and 25-dihydroxyvitamin D in separate groups, and three trials (185 participants; 55% women; mean age 55 years) tested 1,25-dihydroxyvitamin D. Seven trials used placebo, and eight trials used no intervention in the control group. The effect of vitamin D on all-cause mortality at the end of follow-up is uncertain because the results were imprecise (Peto OR 0.70, 95% CI 0.09 to 5.38; I2 = 32%; 15 trials; 1034 participants; very low quality evidence). Trial Sequential Analysis on all-cause mortality was performed based on a mortality rate in the control group of 10%, a relative risk reduction of 28% in the experimental intervention group, a type I error of 2.5%, and type II error of 10% (90% power). There was no diversity. The required information size was 6396 participants. The cumulative Z-curve did not cross the trial sequential monitoring boundary for benefit or harm after the 15th trial, and the Trial Sequential Analyses-adjusted CI was 0.00 to 2534. The effect of vitamin D on liver-related mortality (RR 1.62, 95% CI 0.08 to 34.66; 1 trial; 18 participants) and on serious adverse events such as hypercalcaemia (RR 5.00, 95% CI 0.25 to 100.8; 1 trial; 76 participants), myocardial infarction (RR 0.75, 95% CI 0.08 to 6.81; 2 trials; 86 participants), and thyroiditis (RR 0.33 95% CI 0.01 to 7.91; 1 trial; 68 participants) is uncertain because the results were imprecise. The evidence on all these outcomes is of very low quality. The effect of vitamin D3 on non-serious adverse events such as glossitis (RR 3.70, 95% CI 0.16 to 87.6; 1 trial; 65 participants; very low quality of evidence) is uncertain because the result was imprecise. Due to few data, we did not conduct Trial Sequential Analysis on liver-related mortality, and serious and non-serious adverse events. We found no data on liver-related morbidity and health-related quality of life in the randomised trials included in this review. We are uncertain as to whether vitamin D supplements in the form of vitamin D3, vitamin D2, 1,25-dihydroxyvitamin D, or 25-dihydroxyvitamin D have important effect on all-cause mortality, liver-related mortality, or on serious or non-serious adverse events because the results were imprecise. There is no evidence on the effect of vitamin D supplementation on liver-related morbidity and health-related quality of life. Our conclusions are based on few trials with an insufficient number of participants and on lack of data on clinically important outcomes. In addition, the analysed trials are at high risk of bias with significant intertrial heterogeneity. The overall quality of evidence is very low.

Fifteen trials provided data for this review; 1034 adult participants were randomly assigned to vitamin D compared with placebo or no treatment. Nine trials were conducted in high-income countries, and six trials in middle-income countries. All trials were at high risk of bias (that is overestimation of benefits and underestimation of harms). The age range of the participants was 18 years to 84 years and on average 42% were women. Six trials included participants with chronic hepatitis C, four trials included participants with liver cirrhosis, four trials included participants with non-alcoholic fatty liver disease, and one trial included liver transplant recipients. Most of included trials reported the baseline vitamin D status of participants. Vitamin D administration lasted on average six months and most trials used the cholecalciferol (vitamin D3) form. Six trials appeared to be free of industry sponsorship or other type of for-profit support that may bias the results of the trials. Eight trials may not have been free of for-profit bias as they did not provide any information on clinical trial support or sponsorship. One trial was funded by industry. This review suggests that vitamin D has no beneficial or harmful effects on chronic liver diseases. However, there were too few trials on the individual diagnosis of chronic liver diseases and there were too few participants in the individual trials as well as in our meta-analysis. Therefore, neither benefits nor harms can be excluded. All trials were judged to be at high risk of bias (that is, possibly an overestimation of benefits and underestimation of harms). This evidence is up to date as of January 2017.

10.1002/14651858.CD011564.pub2

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cochrane-simplification-train-2577

We included 11 RCTs in this review update (3352 participants older than 12 years with a diagnosis of CAP); 10 RCTs assessed nine antibiotic pairs (3321 participants) and one RCT assessed four antibiotics (31 participants) in people with CAP. The study quality was generally good, with some differences in the extent of the reporting. A variety of clinical, bacteriological and adverse events were reported. Overall, there was no significant difference in the efficacy of the various antibiotics. Studies evaluating clarithromycin and amoxicillin provided only descriptive data regarding the primary outcome. Though the majority of adverse events were similar between all antibiotics, nemonoxacin demonstrated higher gastrointestinal and nervous system adverse events when compared to levofloxacin, while cethromycin demonstrated significantly more nervous system side effects, especially dysgeusia, when compared to clarithromycin. Similarly, high-dose amoxicillin (1 g three times a day) was associated with higher incidence of gastritis and diarrhoea compared to clarithromycin, azithromycin and levofloxacin. Available evidence from recent RCTs is insufficient to make new evidence-based recommendations for the choice of antibiotic to be used for the treatment of CAP in outpatient settings. Pooling of study data was limited by the very low number of studies assessing the same antibiotic pairs. Individual study results do not reveal significant differences in efficacy between various antibiotics and antibiotic groups. However, two studies did find significantly more adverse events with use of cethromycin as compared to clarithromycin and nemonoxacin when compared to levofloxacin. Multi-drug comparisons using similar administration schedules are needed to provide the evidence necessary for practice recommendations. Further studies focusing on diagnosis, management, cost-effectiveness and misuse of antibiotics in CAP and LRTI are warranted in high-, middle- and low-income countries.

We identified 11 trials (with 3352 participants older than 12 years with a diagnosis of community-acquired pneumonia), fully published in peer-reviewed journals, focused on treatment of pneumonia in adolescents and adults treated in the community in outpatient settings. This included five new trials included since our last review published in 2009. None of the trials included antibiotics versus placebo; all trials included one or more antibiotics. All participants were diagnosed with pneumonia based upon clinical diagnosis by the physician and chest X-ray. All included trials were well conducted; nine of the 11 trials were sponsored by bio-pharmaceutical companies manufacturing the antibiotics used in the study, or their authors were closely linked with the company. Nine of the included trials compared different antibiotics and, hence, we could not combine the results of the individual trials to present our overall conclusion. There were some notable adverse events in seven studies: 1) erythromycin demonstrated significant gastrointestinal side effects compared to clarithromycin in two studies; 2) nemonoxacin demonstrated higher gastrointestinal (nausea, diarrhoea) and nervous system (dizziness, headache) adverse events compared to levofloxacin; 3) cethromycin demonstrated more side effects, especially a distortion of the sense of taste, than clarithromycin; 4) gastritis and diarrhoea were more common in the high-dose amoxicillin group (1 g three times a day) compared to the other three antibiotic groups (clarithromycin, azithromycin and levofloxacin). Unfortunately, there were not enough trials to compare the effects of different antibiotics for pneumonia acquired and treated in the community.

10.1002/14651858.CD002109.pub4

cochrane-simplification-train-2578

cochrane-simplification-train-2578

Eighty studies were identified. Fifty-eight were excluded for various reasons, usually as there was no prospective trial design with randomised treatment allocation. Of the 21 included studies 13 provided data on survival, 7 on tumour response, 16 on measures of QOL or psychological outcomes, or prevalence of chemotherapy-related adverse effects and 12 on side effects of mistletoe treatment; overall comprising 3484 randomised cancer patients. Interventions evaluated were 5 preparations of mistletoe extracts from 5 manufacturers and one commercially not available preparation. The general reporting of RCTs was poor. Of the 13 trials investigating survival, 6 showed some evidence of a benefit, but none of them was of high methodological quality. The results of two trials in patients with melanoma and head and neck cancer gave some evidence that the used mistletoe extracts are not effective for improving survival. Of the 16 trials investigating the efficacy of mistletoe extracts for either improving QOL, psychological measures, performance index, symptom scales or the reduction of adverse effects of chemotherapy, 14 showed some evidence of a benefit, but only 2 of them including breast cancer patients during chemotherapy were of higher methodological quality. Data on side effects indicated that, depending on the dose, mistletoe extracts were usually well tolerated and had few side effects. The evidence from RCTs to support the view that the application of mistletoe extracts has impact on survival or leads to an improved ability to fight cancer or to withstand anticancer treatments is weak. Nevertheless, there is some evidence that mistletoe extracts may offer benefits on measures of QOL during chemotherapy for breast cancer, but these results need replication. Overall, more high quality, independent clinical research is needed to truly assess the safety and effectiveness of mistletoe extracts. Patients receiving mistletoe therapy should be encouraged to take part in future trails.

The review found that there was not enough evidence to reach clear conclusions about the effects on any of these outcomes and it is therefore not clear to what extent the application of mistletoe extracts translates into improved symptom control, enhanced tumour response or prolonged survival. Adverse effects of mistletoe extracts were reported, but appeared to be dose-dependent and primarily confined to reactions at injection site and mild, transient flu-like symptoms. In the absence of good quality, independent trials, decisions about whether mistletoe extracts are likely to be beneficial for a particular problem should rely on expert judgement and practical considerations.

10.1002/14651858.CD003297.pub2

cochrane-simplification-train-2579

cochrane-simplification-train-2579

Our search resulted in 1,148 records, of which two studies described trials that met our inclusion criteria. One trial was a small single-centre Australian trial of 70 antiretroviral-naive participants, while the other trial was a large, multicentre trial, conducted in 14 countries, of 1,216 antiretroviral-naive participants. In both trials over 60% of participants were male. As the therapeutic combinations compared in both trials were not identical, it was not possible to conduct a meta-analysis to increase the power of the results. The main findings, therefore, are from the much larger trial, which was of a high quality. This trial found that there was no statistically significant difference in the efficacy (measured by treatment failure) between nevirapine and efavirenz (EFZ), when used in combination with 3TC and d4T (RR = 1.16; 95%CI: 0.95, 1.41). There was no statistically significant difference between once daily or twice-daily dosing of NVP, when used in combination with 3TC and d4T (RR = 1.00; 95%CI: 0.83; 1.21). It also showed that, compared with NVP plus EFZ, 3TC and d4T, a once-daily dosing of NVP, in combination with 3TC and d4T, performs better in averting treatment failure (RR = 0.82; 95%CI: 0.67, 1.00) than does twice-daily dosing of NVP with 3TC and d4T (RR = 0.82; 95%CI: 0.69; 0.97). Frequency of toxicity was higher in participants receiving NVP, compared with EFZ. The combination of nevirapine, 3TC and d4T is as efficacious as a combination of efavirenz, 3TC and d4T. Once-daily NVP with twice-daily 3TC and d4T is as efficacious as twice-daily NVP, 3TC and d4T. However, toxicity may be increased in the once-daily NVP regime. Additional trials of sufficient duration are required to provide better evidence for the use of this combination as a first line therapy. Ideally, trials should use standardised assessment measures especially with respect to measuring viral load, so that results can be compared and combined in meta-analyses.

People infected with HIV/AIDS require an antiretroviral regimen that works well, has good activity against the virus, has few adverse effects (unintended negative effects of the drug) and that does not interact with other drugs. The regimen of nevirapine, stavudine and lamivudine is widely used as first-line therapy, and is recommended as such by the World Health Organization for so-called low-resource countries (in other words, for poor countries). This review identified two randomised controlled trials that assessed the efficacy of this drug combination. One trial was a small single-centre Australian trial of 70 participants, whereas the other trial was a large, multicentre trial, conducted in 14 countries, of 1,216 participants. In both trials over 60% of participants were male and none had been on previous antiretroviral treatment. As one trial was very small, we cannot be sure of its results. The main findings therefore come from the much larger trial. This trial compared the combination of nevirapine, stavudine and lamivudine with the combination of efavirenz, stavudine and lamivudine, and found that participants had similar treatment outcomes on either combination. It also found that taking nevirapine once a day with twice daily stavudine and lamivudine worked as well as taking nevirapine twice a day in combination with twice daily stavudine and lamivudine. Nevirapine did appear to cause more adverse effects compared with efavirenz, but additional assessment of this is necessary to be more certain. It is important that more trials which follow participants for a longer time be done to provide better evidence for the use of this combination as a first-line therapy. A trial assessing fixed-drug (providing drugs in a single tablet) is also required, as this reduces the number of pills people must take each day. These studies should include assessment of adverse effects, as well as tracking whether resistance to the drugs develop over time.

10.1002/14651858.CD004535.pub2

cochrane-simplification-train-2580

cochrane-simplification-train-2580

Eleven RCTs were identified involving 1067 participants; 568 were randomly allocated to an exercise intervention and 499 to a usual care control group. The majority of participants received treatment for breast cancer (73%). Due to the nature of the intervention, it was not possible to blind the participants or personnel delivering the intervention. The risk of detection bias was either high or unclear in some cases, whilst most other domains were rated as low risk. The included studies were of moderate to very low-certainty evidence. Pooled data demonstrated that exercise training may have little or no difference on physical fitness (VO2 max) compared to usual care (mean difference (MD) 0.05 L/min-1, 95% confidence interval (CI) -0.03 to 0.13; I2 = 0%; 2 studies, 381 participants; low-certainty evidence). Included studies also showed in terms of adverse effects (safety), that it may be of benefit to exercise (8 studies, 507 participants; low-certainty evidence). Furthermore, exercise training probably made little or no difference on HRQoL (EORTC global health status subscale) compared to usual care (MD 2.29, 95% CI -1.06 to 5.65; I2 = 0%; 3 studies, 472 participants; moderate-certainty evidence). However, exercise training probably reduces fatigue (multidimensional fatigue inventory) compared to usual care (MD -1.05, 95% CI -1.83 to -0.28; I2 = 0%; 3 studies, 449 participants moderate-certainty evidence). No studies reported postoperative outcomes. The findings should be interpreted with caution in view of the low number of studies, the overall low-certainty of the combined evidence, and the variation in included cancer types (mainly people with breast cancer), treatments, exercise interventions, and outcomes. Exercise training may, or may not, confer modest benefit on physical fitness and HRQoL. Limited evidence suggests that exercise training is probably not harmful and probably reduces fatigue. These findings highlight the need for more RCTs, particularly in the neoadjuvant setting.

The overall quality (certainty) of the evidence was moderate to very low for all of the outcomes, mainly because of the small number of studies and low number of participants, as well as study limitations. The findings of this review should be interpreted with caution due to the overall low-certainty of the evidence, variation in cancer types and treatments, exercise interventions, and outcomes measured. We are moderately certain that exercise training during adjuvant treatment (chemotherapy or radiotherapy treatment after surgery) reduces fatigue. This is a new area of research, and more information is needed to help us understand whether exercise benefits people undergoing cancer treatment. Future studies should also concentrate on people with a new diagnosis of cancer who have chemotherapy or radiotherapy prior to surgery (known as neoadjuvant treatment), to tell us whether exercise training prior to surgery is important.

10.1002/14651858.CD012280.pub2

cochrane-simplification-train-2581

cochrane-simplification-train-2581

The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. We included seven placebo-controlled studies, two with citalopram, three with fluoxetine and two with paroxetine, with a median study duration of eight weeks (4 to 16 weeks) and 383 participants, who were pooled together. All studies had one or more sources of potential major bias. There was a small (10%) difference in patients who reported a 30% pain reduction between SSRIs (56/172 (32.6%)) and placebo (39/171 (22.8%)) risk difference (RD) 0.10, 95% confidence interval (CI) 0.01 to 0.20; number needed to treat for an additional beneficial outcome (NNTB) 10, 95% CI 5 to 100; and in global improvement (proportion of patients who reported to be much or very much improved: 50/168 (29.8%) of patients with SSRIs and 26/162 (16.0%) of patients with placebo) RD 0.14, 95% CI 0.06 to 0.23; NNTB 7, 95% CI 4 to 17. SSRIs did not statistically, or clinically, significantly reduce fatigue: standard mean difference (SMD) -0.26, 95% CI -0.55 to 0.03; 7.0% absolute improvement on a 0 to 10 scale, 95% CI 14.6% relative improvement to 0.8% relative deterioration; nor sleep problems: SMD 0.03, 95 % CI -0.26 to 0.31; 0.8 % absolute deterioration on a 0 to 100 scale, 95% CI 8.3% relative deterioration to 6.9% relative improvement. SSRIs were superior to placebo in the reduction of depression: SMD -0.39, 95% CI -0.65 to -0.14; 7.6% absolute improvement on a 0 to 10 scale, 95% CI 2.7% to 13.8% relative improvement; NNTB 13, 95% CI 7 to 37. The dropout rate due to adverse events was not higher with SSRI use than with placebo use (23/146 (15.8%) of patients with SSRIs and 14/138 (10.1%) of patients with placebo) RD 0.04, 95% CI -0.06 to 0.14. There was no statistically or clinically significant difference in serious adverse events with SSRI use and placebo use (3/84 (3.6%) in patients with SSRIs and 4/84 (4.8%) and patients with placebo) RD -0.01, 95% CI -0.07 to 0.05. There is no unbiased evidence that SSRIs are superior to placebo in treating the key symptoms of fibromyalgia, namely pain, fatigue and sleep problems. SSRIs might be considered for treating depression in people with fibromyalgia. The black box warning for increased suicidal tendency in young adults aged 18 to 24, with major depressive disorder, who have taken SSRIs, should be considered when appropriate.

Researchers of the Cochrane Collaboration conducted a review of research about the effects of antidepressants classified as serotonin reuptake inhibitors (SSRIs) on fibromyalgia. After searching for all relevant studies up to June 2014, they found seven studies that compared SSRIs with a fake medication. These studies included a total of 383 people. Most participants were middle-aged women. The SSRIs that they studied were citalopram, fluoxetine and paroxetine. Five studies were each funded by pharmaceutical companies, and two studies were funded by public institutions. Key results We are uncertain of the evidence of the outcomes of reduction of pain, sleep problems, fatigue, depression, global improvement (proportion of patients who reported to be much or very much improved), tolerability (dropout rates due to adverse events), and safety (serious adverse events). Possible side effects of SSRIs may include dry mouth, nausea/vomiting, and sexual dysfunction. Rare complications may include allergies, diseases of the immune system, liver damage, and impairment of a person’s ability to drive or operate machinery; serious side effects, such as suicidal thoughts and liver failure, are very rare. What is fibromyalgia and what are serotonin reuptake inhibitors? People with fibromyalgia suffer from chronic widespread pain, sleep problems, and fatigue. There is no cure for fibromyalgia at present. Treatments aim at relieving the symptoms and improving health-related quality of life. Serotonin is a chemical which is produced by the human body and is involved in the experiences of pain, sleep, and mood. Decreased concentrations of serotonin have been reported in people with fibromyalgia. SSRIs are antidepressants that increase the concentration of serotonin in the brain. SSRIs are not approved for use as fibromyalgia treatment, but are approved for depression and anxiety disorder. Quality of the evidence The quality of evidence was very low for each outcome. We downgraded the quality of evidence to very low due to concerns about risk of bias and studies with few participants. Therefore we are uncertain whether taking SSRIs for an average of eight weeks improves fibromyalgia symptoms (number of people who reported that their pain was reduced by at least 30%, and number of people reporting a clinically important global improvement in pain intensity, fatigue, sleep problems, and depression). This is the Abstract and Plain Language Summary of a Cochrane Review, prepared and maintained by The Cochrane Collaboration, currently published in The Cochrane Database of Systematic Reviews 2011 Issue X, Copyright © 2011 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd. The full text of the review is available in The Cochrane Library (ISSN 1464-780X). This record should be cited as: Walitt B, Urrútia G, Nishishinya MB, Riera Lizardo RJ, Cantrell SE, Häuser W. Selective serotonin reuptake inhibitors for fibromyalgia syndrome. Cochrane Database of Systematic Reviews [Year], Issue [Issue].

10.1002/14651858.CD011735

cochrane-simplification-train-2582

cochrane-simplification-train-2582

This review included 35 studies which randomised 10,703 people with CHD (14 trials and 2577 participants added to this update). The population included mainly men (median 77.0%) and people post-MI (mean 65.7%) or after undergoing a revascularisation procedure (mean 27.4%). The mean age of participants within trials ranged from 53 to 67 years. Overall trial reporting was poor, with around a half omitting descriptions of randomisation sequence generation, allocation concealment procedures, or the blinding of outcome assessments. The length of follow-up ranged from six months to 10.7 years (median 12 months). Most studies (23/35) evaluated multifactorial interventions, which included therapies with multiple therapeutic components. Ten studies examined psychological interventions targeted at people with a confirmed psychopathology at baseline and two trials recruited people with a psychopathology or another selecting criterion (or both). Of the remaining 23 trials, nine studies recruited unselected participants from cardiac populations reporting some level of psychopathology (3.8% to 53% with depressive symptoms, 32% to 53% with anxiety), 10 studies did not report these characteristics, and only three studies excluded people with psychopathology. Moderate quality evidence showed no risk reduction for total mortality (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.77 to 1.05; participants = 7776; studies = 23) or revascularisation procedures (RR 0.94, 95% CI 0.81 to 1.11) with psychological therapies compared to usual care. Low quality evidence found no risk reduction for non-fatal MI (RR 0.82, 95% CI 0.64 to 1.05), although there was a 21% reduction in cardiac mortality (RR 0.79, 95% CI 0.63 to 0.98). There was also low or very low quality evidence that psychological interventions improved participant-reported levels of depressive symptoms (standardised mean difference (SMD) -0.27, 95% CI -0.39 to -0.15; GRADE = low), anxiety (SMD -0.24, 95% CI -0.38 to -0.09; GRADE = low), and stress (SMD -0.56, 95% CI -0.88 to -0.24; GRADE = very low). There was substantial statistical heterogeneity for all psychological outcomes but not clinical outcomes, and there was evidence of small-study bias for one clinical outcome (cardiac mortality: Egger test P = 0.04) and one psychological outcome (anxiety: Egger test P = 0.012). Meta-regression exploring a limited number of intervention characteristics found no significant predictors of intervention effects for total mortality and cardiac mortality. For depression, psychological interventions combined with adjunct pharmacology (where deemed appropriate) for an underlying psychological disorder appeared to be more effective than interventions that did not (β = -0.51, P = 0.003). For anxiety, interventions recruiting participants with an underlying psychological disorder appeared more effective than those delivered to unselected populations (β = -0.28, P = 0.03). This updated Cochrane Review found that for people with CHD, there was no evidence that psychological treatments had an effect on total mortality, the risk of revascularisation procedures, or on the rate of non-fatal MI, although the rate of cardiac mortality was reduced and psychological symptoms (depression, anxiety, or stress) were alleviated; however, the GRADE assessments suggest considerable uncertainty surrounding these effects. Considerable uncertainty also remains regarding the people who would benefit most from treatment (i.e. people with or without psychological disorders at baseline) and the specific components of successful interventions. Future large-scale trials testing the effectiveness of psychological therapies are required due to the uncertainty within the evidence. Future trials would benefit from testing the impact of specific (rather than multifactorial) psychological interventions for participants with CHD, and testing the targeting of interventions on different populations (i.e. people with CHD, with or without psychopathologies).

We included 35 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 10,703 participants. Most participants were men (77%), and had recently had a heart attack or undergone a surgical revascularisation procedure. Studies followed up participants for between six months and 10.7 years, with 12 months being the most common period. At baseline (start of the trial), 10 trials only recruited participants with CHD and an established psychological condition (mostly depression), 11 trials recruited people with varying levels of psychopathology, three studies excluded people with psychological conditions, and 11 studies did not report psychological status. Study funding Thirteen studies did not report funding sources. Seven studies were funded by government grants, six through charitable foundations, and six through a mix of government and charitable funding. Two studies reported receiving some funding from private companies in addition to funds secured from government and charitable sources, and one study was university funded. Key results Psychological interventions did not reduce mortality (any cause), or the risk cardiac surgery or having another heart attack. Psychological interventions reduced the risk of cardiac deaths and reduced participant-reported symptoms of depression, anxiety, and stress. Quality of the evidence There is considerable uncertainty regarding the effects observed, as the quality of the evidence was either low (for cardiac mortality, non-fatal heart attack, depression, anxiety) or very low (for stress) for most measures, except deaths (any cause) or cardiac surgery, both of which had moderate quality of evidence.

10.1002/14651858.CD002902.pub4

cochrane-simplification-train-2583

cochrane-simplification-train-2583

Twenty-five RCTs (2310 participants) were included in the review. Fourteen studies were judged to be at high risk of bias due to lack of blinding, incomplete outcome data and selective reporting. Meta-analysis of two studies (101 patients) comparing polyethylene glycol (PEG) with placebo showed a significantly increased number of stools per week with PEG (MD 2.61 stools per week, 95% CI 1.15 to 4.08). Common adverse events in the placebo-controlled studies included flatulence, abdominal pain, nausea, diarrhoea and headache. Participants receiving high dose PEG (0.7 g/kg) had significantly more stools per week than low dose PEG (0.3 g/kg) participants (1 study, 90 participants, MD 1.30, 95% 0.76 to 1.84). Meta-analysis of 6 studies with 465 participants comparing PEG with lactulose showed a significantly greater number of stools per week with PEG (MD 0.70 , 95% CI 0.10 to 1.31), although follow-up was short. Patients who received PEG were significantly less likely to require additional laxative therapies. Eighteen per cent (27/154) of PEG patients required additional therapies compared to 31% (47/150) of lactulose patients (RR 0.55, 95% CI 0.36 to 0.83). No serious adverse events were reported with either agent. Common adverse events in these studies included diarrhoea, abdominal pain, nausea, vomiting and pruritis ani. Meta-analysis of 3 studies with 211 participants comparing PEG with milk of magnesia showed that the stools per week were significantly greater with PEG (MD 0.69, 95% CI 0.48 to 0.89). However, the magnitude of this difference was quite small and may not be clinically significant. One child was noted to be allergic to PEG, but there were no other serious adverse events reported. One study found a significant difference in stools per week favouring milk of magnesia over lactulose (MD -1.51, 95% CI -2.63 to -0.39, 50 patients), Meta-analysis of 2 studies with 287 patients comparing liquid paraffin (mineral oil) with lactulose revealed a relatively large statistically significant difference in the number of stools per week favouring liquid paraffin (MD 4.94 , 95% CI 4.28 to 5.61). No serious adverse events were reported. Adverse events included abdominal pain, distention and watery stools. No statistically significant differences in the number of stools per week were found between PEG and enemas (1 study, 90 patients, MD 1.00, 95% CI -1.58 to 3.58), dietary fibre mix and lactulose (1 study, 125 patients, P = 0.481), senna and lactulose (1 study, 21 patients, P > 0.05), lactitol and lactulose (1 study, 51 patients, MD -0.80, 95% CI -2.63 to 1.03), hydrolyzed guar gum and lactulose (1 study, 61 patients, MD 1.00, 95% CI -1.80 to 3.80), PEG and flixweed (1 study, 109 patients, MD 0.00, 95% CI -0.33 to 0.33), PEG and dietary fibre (1 study, 83 patients, MD 0.20, 95% CI -0.64 to 1.04), and PEG and liquid paraffin (2 studies, 261 patients, MD 0.35, 95% CI -0.24 to 0.95). The pooled analyses suggest that PEG preparations may be superior to placebo, lactulose and milk of magnesia for childhood constipation. GRADE analyses indicated that the overall quality of the evidence for the primary outcome (number of stools per week) was low or very low due to sparse data, inconsistency (heterogeneity), and high risk of bias in the studies in the pooled analyses. Thus, the results of the pooled analyses should be interpreted with caution because of quality and methodological concerns, as well as clinical heterogeneity, and short follow-up. There is also evidence suggesting the efficacy of liquid paraffin (mineral oil). There is no evidence to demonstrate the superiority of lactulose when compared to the other agents studied, although there is a lack of placebo controlled studies. Further research is needed to investigate the long term use of PEG for childhood constipation, as well as the role of liquid paraffin. The optimal dose of PEG also warrants further investigation.

This review included 25 studies with a total of 2310 children that compared ten different agents to either placebo (inactive medications) or each other. Many of the studies were small in size and were judged to be of poor or unclear quality. The results of this review suggest that PEG preparations may increase the frequency of bowel movements in constipated children. There is evidence from one study that suggests that high dose PEG (0.7 g/kg) may be superior to low dose PEG (0.3 g/kg) for increasing the frequency of bowel movements in constipated children. The rates of minor side effects were generally lower compared to other agents. Common side effects included flatulence, abdominal pain, nausea, diarrhoea and headache. There was also some evidence that liquid paraffin (mineral oil) increased the frequency of bowel movements in constipated children. Common side effects with liquid paraffin included abdominal pain, distention and watery stools. There was no evidence to suggest that lactulose is superior to the other agents studied, although there were no trials comparing it to placebo (a fake medicine such as a sugar pill). These studies were relatively short in duration and so it is difficult to assess the long term effectiveness of these agents for the treatment of childhood constipation. Long term effectiveness is important, given the often chronic nature of this problem in children. The results of the review should be interpreted with caution due to quality issues in the included studies. As such, the strength of our conclusions is extremely limited and more research is needed. Key questions that need addressing include the safety of liquid paraffin, given its apparent effectiveness, but limited investigation. In particular, future research should compare liquid paraffin to PEG. The optimal dose of PEG warrants further investigation. The role of PEG for the long term management of chronic constipation also needs further investigation to allow research to better inform actual clinical practice. There is a lack of studies comparing lactulose with placebo.

10.1002/14651858.CD009118.pub3

cochrane-simplification-train-2584

cochrane-simplification-train-2584

We included five randomised controlled trials with a total of 212 participants in the analyses. All included participants were under five years of age. Using GRADE, we assessed there was low-quality evidence for all analysed outcomes. We assessed high risk of performance and detection bias for two studies due to their unblinded setting. Levosimendan showed no clear effect on risk of mortality (risk ratio (RR) 0.47, 95% confidence interval (CI) 0.12 to 1.82; participants = 123; studies = 3) and no clear effect on low cardiac output syndrome (RR 0.64, 95% CI 0.39 to 1.04; participants = 83; studies = 2) compared to standard treatments. Data on time-to-death were not available from any of the included studies. There was no conclusive evidence on the effect of levosimendan on the secondary outcomes. The length of intensive care unit stays (mean difference (MD) 0.33 days, 95% CI -1.16 to 1.82; participants = 188; studies = 4), length of hospital stays (MD 0.26 days, 95% CI -3.50 to 4.03; participants = 75; studies = 2), duration of mechanical ventilation (MD -0.04 days, 95% CI -0.08 to 0.00; participants = 208; studies = 5), and the risk of mechanical circulatory support or cardiac transplantation (RR 1.49, 95% CI 0.19 to 11.37; participants = 60; studies = 2) did not clearly differ between the groups. Published data about adverse effects of levosimendan were limited. A meta-analysis of hypotension, one of the most feared side effects of levosimendan, was not feasible because of the heterogeneous expression of blood pressure values. The current level of evidence is insufficient to judge whether prophylactic levosimendan prevents low cardiac output syndrome and mortality in paediatric patients undergoing surgery for congenital heart disease. So far, no significant differences have been detected between levosimendan and standard inotrope treatments in this setting. The authors evaluated the quality of evidence as low, using the GRADE approach. Reasons for downgrading were serious risk of bias (performance and detection bias due to unblinded setting of two RCTs), serious risk of inconsistency, and serious to very serious risk of imprecision (small number of included patients, low event rates).

We identified five studies that had a total of 212 patients. All patients were under five years of age. The patients were given levosimendan during or immediately after heart surgery for a duration of 20 to 72 hours. They were monitored for 20 hours to six days. We asked all of the study authors for additional information about their trials. All but one author responded. The evidence is current to June 2016. We found low-quality evidence for all outcomes. This was mainly due to the small number of included patients (high imprecision of results). Thus, all results of the meta-analysis must be viewed with caution. The available data revealed no clear difference between levosimendan and conventional medication in preventing reduced heart function and death after heart surgery in the studied population. We also found no clear difference in the length of stay in the intensive care unit. The available data did not allow us to judge whether one of the treatment arms was superior to the other for three secondary outcomes: length of hospital stay, time on mechanical ventilation, need to implant circulatory support devices or the need for cardiac transplantation. Overall, few side effects were reported in any of the groups. We were unable to pool data to generate useful information about the safety of levosimendan.

10.1002/14651858.CD011312.pub3

cochrane-simplification-train-2585

cochrane-simplification-train-2585

We included nine RCTs (911 participants), including four different comparisons. None of the studies evaluated our first primary outcome measure, disease-specific HRQL. Fluticasone propionate versus beclomethasone dipropionate We identified two small studies (56 participants with polyps) that evaluated disease severity and looked at the primary adverse effect: epistaxis , but no other outcomes. We cannot report any numerical data but the study authors reported no difference between the two steroids. The evidence was of very low quality. Fluticasone propionate versus mometasone furoate We identified only one study (100 participants with polyps) that evaluated disease severity (nasal symptoms scores), which reported no difference (no numerical data available). The evidence was of very low quality. High-dose versus low-dose steroids We included five studies (663 participants with nasal polyps), three using mometasone furoate (400 µg versus 200 µg in adults and older children, 200 µg versus 100 µg in younger children) and two using fluticasone propionate drops (800 µg versus 400 µg). We found low quality evidence relating to disease severity and nasal polyps size, with results from the high-dose and low-dose groups being similar. Although all studies reported more improvement in polyp score in the high-dose group, the significance of this is unclear due to the small size of the improvements. The primary adverse effect, epistaxis , was more common when higher doses were used (risk ratio (RR) 2.06, 95% confidence interval (CI) 1.20 to 3.54, 637 participants, moderate quality evidence). Most of the studies that contributed data to this outcome used a broad definition of epistaxis, which ranged from frank bleeding to bloody nasal discharge to flecks of blood in the mucus. Aqueous nasal spray versus aerosol spray We identified only one poorly reported study (unclear number of participants for comparison of interest, 91 between three treatment arms), in which there were significant baseline differences between the participants in the two groups. We were unable to draw meaningful conclusions from the data. We found insufficient evidence to suggest that one type of intranasal steroid is more effective than another in patients with chronic rhinosinusitis, nor that the effectiveness of a spray differs from an aerosol. We identified no studies that compared drops with spray. It is unclear if higher doses result in better symptom improvements (low quality evidence), but there was moderate quality evidence of an increased risk of epistaxis as an adverse effect of treatment when higher doses were used. This included all levels of severity of epistaxis and it is likely that the proportion of events that required patients to discontinue usage is low due to the low numbers of withdrawals attributed to it. If epistaxis is limited to streaks of blood in the mucus it may be tolerated by the patient and it may be safe to continue treatment. However, it may be a factor that affects compliance. There is insufficient evidence to suggest that the different types of corticosteroid molecule or spray versus aerosol have different effects. Lower doses have similar effectiveness but fewer side effects. Clearly more research in this area is needed, with specific attention given to trial design, disease-specific health-related quality of life outcomes and evaluation of longer-term outcomes and adverse effects.

We included nine randomised controlled trials (RCTs) with a total of 910 participants in this review. The studies varied in size: some were small, with as few as 20 patients, while others included over 200 participants. Most studies recruited adult patients, but one study only included children. In the majority of the adult studies, most participants were male (72% to 79%). In all of the studies the participants had chronic rhinosinusitis with nasal polyps. The studies either compared different types of steroids (three studies), high-dose versus low-dose steroids (five studies), twice daily versus once daily steroids, or different delivery methods (aqueous nasal spray versus aerosol - one study). All of the studies had a placebo group. Different steroids: fluticasone propionate versus beclomethasone dipropionate Two small studies (56 participants, unclear risk of bias) evaluated disease severity and looked at the primary adverse effect, epistaxis (nosebleed), but no other outcomes. No difference was found between the two steroids but we assessed the evidence to be of very low quality. Different steroids: fluticasone propionate versus mometasone furoate One study (100 participants, unclear risk of bias) found no difference in disease severity (nasal symptoms scores). We assessed this evidence to be of very low quality. High-dose versus low-dose steroids We found five studies (663 participants, low or unclear risk of bias) that compared high-dose and low-dose steroids, three using mometasone furoate (400 µg versus 200 µg in adults and older children, 200 µg versus 100 µg in younger children), and two using fluticasone propionate drops (800 µg versus 400 µg). Effectiveness (disease severity and nasal polyps size) was similar between the high-dose and low-dose groups (low quality evidence). Although all studies reported more improvement in polyp score in the high-dose group, the significance of this is unclear because the improvements seen were small. The primary adverse effect, epistaxis, was more common when higher doses were used (moderate quality evidence). Different delivery methods: aqueous nasal spray versus aerosol spray We identified only one poorly reported study with a high risk of bias. It was unclear how many participants there were: 91 were recruited into three arms. There had also been significant differences between the participants in the two groups when they started the study. We were unable to draw any meaningful conclusions from this study. We found no evidence that one type of intranasal steroid is more effective than another in patients with chronic rhinosinusitis, nor that higher doses are better than lower, nor that the effectiveness of a spray differs from an aerosol. We found no studies that compared nasal drops with spray. We did find moderate quality evidence of an increased risk of epistaxis (nosebleed) as an adverse effect of treatment when higher doses were used. More research in this area is clearly needed. In the future studies should be well designed: they should measure chronic rhinosinusitis-specific health-related quality of life and adverse effects as outcomes, and look at what happens to patients taking intranasal steroids in the longer term.

10.1002/14651858.CD011993.pub2

cochrane-simplification-train-2586

cochrane-simplification-train-2586

We included four randomized trials involving 200 participants. Owing to small numbers of studies and participants, it was not possible to combine data for all outcomes. Two trials reported 28-day mortality, and one trial reported hospital mortality; in the third trial, the number of deaths stated did not match the quoted mortality rates. The pooled risk ratio (95% confidence interval) for 28-day mortality associated with HVHF was 0.89 (0.60 to 1.32, two trials, 146 participants, low-quality evidence). One study (137 participants, low-quality evidence) reported length of stay in the ICU. Two trials (170 participants, low-quality evidence) reported organ dysfunction, but we could not pool results owing to reporting differences. Three studies (189 participants, low-quality evidence) reported on haemodynamic changes, but we could not pool results owing to reporting differences. Investigators reported no adverse events. Overall, the included studies had low risk of bias. Investigators reported no adverse effects of HVHF (low-quality evidence). The results of this meta-analysis show that very few studies have been conducted to investigate the use of HVHF in critically ill patients with severe sepsis or septic shock (four studies, 201 participants, low-quality evidence). Researchers should consider additional randomized controlled trials that are large and multi-centred and have clinically relevant outcome measures. The cost-effectiveness of HVHF should also be studied..

This review is current until December 2015. We included four trials involving 205 participants. All four studies assessed effects of HVHF compared with the current standard haemofiltration and included participants with severe sepsis or septic shock who had been admitted to an ICU. Three of the four studies were very small (fewer than 20 participants enrolled in each study). The maximum time that participants were followed up after inclusion in any of the studies was 28 days. Two studies received financial support from pharmaceutical companies, and one study received support from a health research organization. Key results Outcome data were limited - two trials reported death rates at 28 days and one reported death rates in hospital; in the fourth study, the number of deaths stated did not match the quoted mortality rates. One study reported length of stay in the ICU, and one provided data on organ dysfunction. Investigators described no complications. No clear evidence showed any benefit of HVHF in critically ill patients with severe sepsis or septic shock. Quality of evidence Evidence is insufficient to support the routine use of high-volume haemofiltration in patients with severe sepsis or septic shock. Studies included in this review reported relatively small numbers of participants and measured different outcomes; therefore, we judged the quality of evidence with respect to the impact of HVHF as low. Larger trials, carried out at many centres, are required for full assessment of clinically relevant outcomes and for evaluation of cost versus benefit.

10.1002/14651858.CD008075.pub3

cochrane-simplification-train-2587

cochrane-simplification-train-2587

One randomised controlled trial with a total of 100 male participants was included in the review. The trial compared hand-assisted laparoscopic repair with EVAR and provided results for in-hospital mortality, operative time, length of hospital stay and lower limb ischaemia. The included study did not report on the other pre-planned outcomes of this review. No in-hospital deaths occurred in the study. Hand-associated laparoscopic repair was associated with a longer operative time (MD 53.00 minutes, 95% CI 36.49 to 69.51) than EVAR. The incidence of lower limb ischaemia was similar between the two treatment groups (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.05 to 5.34). The mean length of hospital stay was 4.2 days and 3.4 days in the hand-assisted laparoscopic repair and EVAR groups respectively but standard deviations were not reported and therefore it was not possible to independently test the statistical significance of this result. The quality of evidence was downgraded for imprecision due to the inclusion of one small study; and wide confidence intervals and indirectness due to the study including male participants only. No study compared laparoscopic repair (total or hand-assisted) with open surgical repair or total laparoscopic surgical repair with EVAR. There is insufficient evidence to draw any conclusions about effectiveness and safety of laparoscopic (total and hand-assisted) surgical repair of AAA versus open surgical repair or EVAR, because only one small randomised trial was eligible for inclusion in this review. High-quality randomised controlled trials are needed.

One randomised controlled trial (current until August 2016), studying 100 male participants and comparing hand-assisted laparoscopic repair with EVAR, was included in this review. No in-hospital deaths occurred during the study. The trial showed that hand-assisted laparoscopic repair took longer to perform than EVAR but there was no difference in the number of patients with reduced blood flow to the leg following either treatment. At present, there is a lack of randomised controlled trials examining the comparative effectiveness and safety of laparoscopic repair of AAA. The quality of the available evidence was imprecise due to the inclusion of one small study and wide confidence intervals; and indirect because the study includes male participants only. Further research is required before conclusions can be made.

10.1002/14651858.CD012302.pub2

cochrane-simplification-train-2588

cochrane-simplification-train-2588

The search identified 35 references, with 25 studies, but we could only include two studies with a total of 358 participants. The studies had a moderate risk of bias, and therefore risk overestimating any positive effects of ICT-based prompting. Both included studies compared semi-automatised ICT-based prompting intervention with standard care groups in mental health outpatient care. The interventions were SMS-message and an electronic assistant device. One included study reported our primary outcome, compliance. There was not any clear evidence that ICT-based prompts increase improvement in compliance (stop taking medication within six months n = 320, RR 1.11 CI 0.96 to 1.29, moderate quality evidence). There was some low quality evidence that ICT-based prompts have small effects for: mental state (average change in specific symptom scores within three months n = 251, MD -0.30 CI -0.53 to -0.07; severity of illness within three months n = 251, MD -0.10 CI -0.13 to -0.07 and six months n = 251, MD -0.10 CI -0.13 to -0.07; average change in depressive scores within six months n = 251, RR 0.00 CI -0.28 to 0.28; global symptoms within three months n = 251, MD -0.10 CI -0.38 to -0.07; negative symptoms within three months n = 251, MD -0.10 CI -0.38 to 0.18 and six months n = 251, MD -0.30 CI -0.58 to 0.02, low quality evidence). Level of insight improved more among people receiving ICT-based prompt compared with those in the control group at six months (n = 251, MD -0.10 CI -0.13 to -0.07). ICT-based prompts also increased quality of life (average change in quality of life within six months n = 251, RR 0.50 CI 0.19 to 0.81, moderate quality evidence). Based on the existing data, there is no evidence that either intervention is less acceptable than the other (n = 347, 2 RCTs, RR 1.46 CI 0.70 to 3.05, low quality evidence). Included studies did not report outcomes of service utilisation, behaviour, costs or adverse events. The evidence base on the effects of ICT-based prompts is still inconclusive. Data to clarify ICT-based prompting effects are awaited from an ongoing trial, but further well-conducted trials considering the different ICT-based prompts are warranted.

People with severe mental health problems often have difficulties with 'treatment compliance' i.e. following their treatment programme. They can have difficulty remembering to take medication or appointment times. Unpleasant side effects of medication can also lead to people stopping medication, and a lack of insight into their illness can mean they do not see the need to follow treatments. Non-compliance with treatment can lead to poor health outcomes and even relapses and hospitalisation. There are several methods healthcare professionals use to help people with serious mental illness improve compliance; once such method is prompting. The purpose of prompting is to help patients to follow the treatment instructions and keep the treatment appointment times by using reminders via telephone calls, personal visits or posted referral letter. More recently, Information and technology-based prompts are being used. This review investigates the effectiveness of ICT-based prompts in order to support treatment compliance among patients with serious mental illness. A search for randomised controlled trials was run in 2012. Two trials that compared the use of ICT prompting compared with standard care could be included. Review authors rated the quality of data in these as 'moderate' or 'low'. Because of the small amount of data, it is impossible to say whether ICT-based prompts are effective. Only one trial measured medication compliance. The study suggested that ICT-based prompts may help people take their medication, but clear evidence of a benefit is missing. There were some positive effects for patient insight. However, insight was only better in the medium term and appeared to show no difference in the short term. Further, some positive effect was found in patient satisfaction with treatment, although the results for the analyses were imprecise. Also, mental state and quality of life showed minor improvement. There were no clear evidence that either intervention is less acceptable than the other. Outcomes such as service use, behaviour, costs or adverse effects were not presented in the studies. There is an ongoing trial, but additional well-conducted trials are needed.

10.1002/14651858.CD009960.pub2

cochrane-simplification-train-2589

cochrane-simplification-train-2589

Two randomised controlled trials were identified, both were conducted in patients with yellow oleander poisoning. One trial investigated the effect of MDAC on mortality, the relative risk (RR) was 0.31 (95% confidence interval (CI) 0.12 to 0.83) indicating a beneficial effect. The second study found a beneficial effect of anti-digoxin Fab antitoxin on the presence of cardiac dysrhythmias at two hours post-administration; the RR was 0.60 (95% CI 0.44 to 0.81). Other benefits were also noted in both studies and serious adverse effects were minimal. Studies assessing the effect of antidotes on other cardenolides were not identified. One ongoing study investigating the activated charcoal for acute yellow oleander self-poisoning was also identified. There is some evidence to suggest that MDAC and anti-digoxin Fab antitoxin may be effective treatments for yellow oleander poisoning. However, the efficacy and indications of these interventions for the treatment of acute digitalis poisoning is uncertain due to the lack of good quality controlled clinical trials. Given pharmacokinetic differences between individual cardenolides, the effect of antidotes administered to patients with yellow oleander poisoning cannot be readily translated to those of other cardenolides. Unfortunately cost limits the use of antidotes such as anti-digoxin Fab antitoxin in developing countries where cardenolide poisonings are frequent. More research is required using relatively cheap antidotes which may also be effective.

Two randomised controlled trials were identified; both were conducted in patients with yellow oleander poisoning. One trial investigated the effect of MDAC on mortality, the relative risk (RR) was 0.31 (95% confidence interval (CI) 0.12 to 0.83) indicating a beneficial effect. The second study found a beneficial effect of anti-digoxin Fab antitoxin on the presence of cardiac dysrhythmias at two hours post-administration; the RR was 0.60 (95% CI 0.44 to 0.81). Other benefits were also noted in both studies and serious adverse effects were minimal. Studies assessing the effect of antidotes on other cardenolides were not identified. One ongoing study investigating the activated charcoal for acute yellow oleander self-poisoning was also identified. There is some evidence to suggest that MDAC and anti-digoxin Fab antitoxin may be effective treatments for yellow oleander poisoning. However, the efficacy and indications of these interventions for the treatment of acute digitalis poisoning is uncertain due to the lack of good quality controlled clinical trials. Given pharmacokinetic differences between individual cardenolides, the effect of antidotes administered to patients with yellow oleander poisoning cannot be readily translated to those of other cardenolides. Unfortunately cost limits the use of antidotes such as anti-digoxin Fab antitoxin in developing countries where cardenolide poisonings are frequent. More research is required using relatively cheap antidotes which may also be effective.

10.1002/14651858.CD005490.pub2

cochrane-simplification-train-2590

cochrane-simplification-train-2590

Nine trials, including 4654 participants, met our inclusion criteria. Five trials evaluated appointment reminders for people on treatment for active TB, two for people on prophylaxis for latent TB, and four for people undergoing TB screening using skin tests. We classified the interventions into 'pre-appointment' reminders (telephone calls or letters prior to a scheduled appointment) or 'default' reminders (telephone calls, letters, or home visits to people who had missed an appointment). For people being treated for active TB, clinic attendance and TB treatment completion were higher in people receiving pre-appointment reminder phone-calls (clinic attendance: 66% versus 50%; RR 1.32, 95% CI 1.10 to 1.59, one trial (USA), 615 participants, low quality evidence; TB treatment completion: 100% versus 88%; RR 1.14, 95% CI 1.02 to 1.27, one trial (Thailand), 92 participants, low quality evidence). Clinic attendance and TB treatment completion were also higher with default reminders (letters or home visits) (clinic attendance: 52% versus 10%; RR 5.04, 95% CI 1.61 to 15.78, one trial (India), 52 participants, low quality evidence; treatment completion: RR 1.17, 95% CI 1.11 to 1.24, two trials (Iraq and India), 680 participants, moderate quality evidence). For people on TB prophylaxis, clinic attendance was higher with a policy of pre-appointment phone-calls (63% versus 48%; RR 1.30, 95% CI 1.07 to 1.59, one trial (USA), 536 participants); and attendance at the final clinic was higher with regular three-monthly phone-calls or nurse visits (93% versus 65%, one trial (Spain), 318 participants). For people undergoing screening for TB, three trials of pre-appointment phone-calls found little or no effect on the proportion of people returning to clinic for the result of their skin test (three trials, 1189 participants, low quality evidence), and two trials found little or no effect with take home reminder cards (two trials, 711 participants). All four trials were conducted among healthy volunteers in the USA. Policies of sending reminders to people pre-appointment, and contacting people who miss appointments, seem sensible additions to any TB programme, and the limited evidence available suggests they have small but potentially important benefits. Future studies of modern technologies such as short message service (SMS) reminders would be useful, particularly in low-resource settings.

This Cochrane Review summarizes trials evaluating the effects of reminder systems on attendance at tuberculosis (TB) clinics and completion of TB treatment. After searching for relevant trials up to 29 August 2014, we included nine trials, including 4654 people. What are reminder systems and how might they help? Effective treatment for TB requires people to take multiple drugs daily for at least six months. Consequently, once they start to feel well again, some patients stop attending clinics and stop taking their medication which can lead to the illness returning and the development of drug resistance. One strategy the World Health Organization recommends is that an appointed person (a health worker or volunteer) watches the person take their medication everyday (called direct observation). Other strategies include reminder systems to prompt patients to attend for appointments on time, or to re-engage people who have missed or defaulted on a scheduled appointment. These prompts may be in the form of telephone calls or letters before the next scheduled appointment ("pre-appointment reminders"), or phone calls, letters, or home visits after a missed appointment ("default reminders"). What the research says: For people being treated for active TB: - More people attended the clinic and completed TB treatment with pre-appointment reminder phone-calls (low quality evidence). - More people attended the clinic and completed TB treatment with a policy of default reminders (low and moderate quality evidence respectively). For people on TB prophylaxis: - More people attended the clinic with pre-appointment phone-calls, and the number attending the final clinic was higher with three-monthly phone-calls or nurse home visits. For people undergoing screening for TB: - Similar numbers of people attended clinic for skin test reading with and without pre-appointment phone-calls (low quality evidence). - Similar numbers of people attended clinic for skin test reading with and without take home reminder cards.

10.1002/14651858.CD006594.pub3

cochrane-simplification-train-2591

cochrane-simplification-train-2591

Only one study fulfilled the criteria (Amato 1988). 20 full term babies requiring exchange transfusion for hemolytic jaundice due to ABO incompatibility were randomly allocated to receive single or double volume exchange transfusion. Base line characteristics of both groups were similar with regards to birth weight 3260 (SD 390) g vs. 3350 SD (410) g, gestational age 39 (SD 1) week vs. 40 (SD 0.8) week, immediate pre exchange bilirubin level 199 (SD 33) micromol/L vs. 216 (SD 55) micromol/L. Both groups were treated equally apart from the volume of blood used for exchange transfusion. Total bilirubin levels immediately after exchange transfusion were not significantly different in either group. No long term neurodevelopmental outcome was examined in this study. There was insufficient evidence to support or refute the use of single volume exchange transfusion as opposed to double volume exchange transfusion in jaundiced newborns. A change from the current practice of double volume exchange transfusions for severe jaundice in newborns infant, cannot be recommended on current evidence.

This review was undertaken to examine if single volume (removal of blood equivalent to the blood volume of the baby) is as effective as double volume (removal of twice blood volume of the baby) in reducing the brain damage and bilirubin levels in newborn infants with severe jaundice. Only one randomised trial fulfilled the criteria for inclusion in the analysis. This study compared single and double volume exchange transfusion in jaundice due to ABO hemolytic jaundice. The study found no significant difference in bilirubin levels following exchange. This study did not look at any long term neurodevelopmental outcome (brain damage). Based on the available data, there is insufficient evidence to support or refute the use of single volume exchange transfusion as opposed to double volume exchange transfusion in jaundiced newborns.

10.1002/14651858.CD004592.pub2

cochrane-simplification-train-2592

cochrane-simplification-train-2592

Twelve trials involving 844 participants were included. One trial tested two comparisons. Quality assessment revealed a poor level of methodological rigour in many studies, particularly with regard to concealment of allocation and the lack of assessor blinding. Open surgical treatment compared with non-surgical treatment (6 trials, 536 participants) was associated with a statistically significant lower risk of rerupture (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.21 to 0.77), but a higher risk of other complications including infection (RR 4.89, 95% CI 1.09 to 21.91), adhesions and disturbed skin sensibility (numbness). Functional status including sporting activity was variably and often incompletely reported, including frequent use of non standardised outcome measures, and the results were inconclusive. Open surgical repair compared with percutaneous repair (4 trials, 174 participants) was associated with a higher risk of infection (RR 9.32, 95% CI 1.77 to 49.16). These figures should be interpreted with caution because of the small numbers involved. Similarly, no definitive conclusions could be made regarding different tendon repair techniques (3 trials, 147 participants). Open surgical treatment of acute Achilles tendon ruptures significantly reduces the risk of rerupture compared with non-surgical treatment, but produces significantly higher risks of other complications, including wound infection. The latter may be reduced by performing surgery percutaneously.

Twelve trials including 794 participants acute Achilles tendon rupture were included. The majority of participants were male, and the average ages of the study populations were between 36 to 41 years. Many of the trials had flawed methods that undermined the reliability of their results. Open surgical treatment compared with non-surgical treatment (6 studies, 502 participants) was associated with a lower risk of rerupture, but a higher risk of other complications such as infection, adhesions and disturbed skin sensibility (numbness and tingling). There were insufficient and inconclusive data on function and sporting activities. Percutaneous repair (involving stab incisions through which the repair suture is passed through without direct exposure of the tendon) compared with open repair (4 studies, 174 participants) was associated with a lower risk of infection. These figures should be interpreted with caution because of the small numbers involved. Similarly, no definitive conclusions could be made regarding different tendon repair techniques (3 studies, 141 participants).

10.1002/14651858.CD003674.pub4

cochrane-simplification-train-2593

cochrane-simplification-train-2593

For this update, we added 11 studies and included a total of 20 studies (1477 participants). Rehabilitation programmes showed great diversity in terms of exercise training (number of completed exercise sessions; type, intensity and supervision), patient education (from none to extensive self-management programmes) and how they were organised (within one setting, e.g. pulmonary rehabilitation, to across several settings, e.g. hospital, outpatient centre and home). In eight studies, participants completed extensive pulmonary rehabilitation, and in 12 studies, participants completed pulmonary rehabilitation ranging from not extensive to moderately extensive. Eight studies involving 810 participants contributed data on hospital readmissions. Moderate-quality evidence indicates that pulmonary rehabilitation reduced hospital readmissions (pooled odds ratio (OR) 0.44, 95% confidence interval (CI) 0.21 to 0.91), but results were heterogenous (I2 = 77%). Extensiveness of rehabilitation programmes and risk of bias may offer an explanation for the heterogeneity, but subgroup analyses were not statistically significant (P values for subgroup effects were between 0.07 and 0.11). Six studies including 670 participants contributed data on mortality. The quality of evidence was low, and the meta-analysis did not show a statistically significant effect of rehabilitation on mortality (pooled OR 0.68, 95% CI 0.28 to 1.67). Again, results were heterogenous (I2 = 59%). Subgroup analyses showed statistically significant differences in subgroup effects between trials with more and less extensive rehabilitation programmes and between trials at low and high risk for bias, indicating possible explanations for the heterogeneity. Hospital readmissions and mortality studies newly included in this update showed, on average, significantly smaller effects of rehabilitation than were seen in earlier studies. High-quality evidence suggests that pulmonary rehabilitation after an exacerbation improves health-related quality of life. The eight studies that used St George's Respiratory Questionnaire (SGRQ) reported a statistically significant effect on SGRQ total score, which was above the minimal important difference (MID) of four points (mean difference (MD) -7.80, 95% CI -12.12 to -3.47; I2 = 64%). Investigators also noted statistically significant and important effects (greater than MID) for the impact and activities domains of the SGRQ. Effects were not statistically significant for the SGRQ symptoms domain. Again, all of these analyses showed heterogeneity, but most studies showed positive effects of pulmonary rehabilitation, some studies showed large effects and others smaller but statistically significant effects. Trials at high risk of bias because of lack of concealment of random allocation showed statistically significantly larger effects on the SGRQ than trials at low risk of bias. High-quality evidence shows that six-minute walk distance (6MWD) improved, on average, by 62 meters (95% CI 38 to 86; I2 = 87%). Heterogeneity was driven particularly by differences between studies showing very large effects and studies showing smaller but statistically significant effects. For both health-related quality of life and exercise capacity, studies newly included in this update showed, on average, smaller effects of rehabilitation than were seen in earlier studies, but the overall results of this review have not changed to an important extent compared with results reported in the earlier version of this review. Five studies involving 278 participants explicitly recorded adverse events, four studies reported no adverse events during rehabilitation programmes and one study reported one serious event. Overall, evidence of high quality shows moderate to large effects of rehabilitation on health-related quality of life and exercise capacity in patients with COPD after an exacerbation. Some recent studies showed no benefit of rehabilitation on hospital readmissions and mortality and introduced heterogeneity as compared with the last update of this review. Such heterogeneity of effects on hospital readmissions and mortality may be explained to some extent by the extensiveness of rehabilitation programmes and by the methodological quality of the included studies. Future researchers must investigate how the extent of rehabilitation programmes in terms of exercise sessions, self-management education and other components affects the outcomes, and how the organisation of such programmes within specific healthcare systems determines their effects after COPD exacerbations on hospital readmissions and mortality.

We included 20 studies involving 1477 participants with COPD. Rehabilitation programmes started in hospital in some trials and after discharge in others. These programmes showed great diversity in terms of exercise training (e.g. number of completed exercise sessions, type and intensity of exercise training), patient education (none to extensive self-management programmes) and how programmes were organised (within one setting, e.g. pulmonary rehabilitation, to across several settings, e.g. hospital, outpatient centre and home). Quality of life and exercise capacity were improved by rehabilitation, and the effect was substantially larger than the minimal important difference. Results for hospital readmissions and mortality were diverse, with some studies showing that pulmonary rehabilitation reduced hospital admissions and mortality compared with usual community care (no rehabilitation), and other studies not showing such effects. Uncertainty about reasons for differences across trials in terms of hospital readmissions and mortality led to downgrading of the quality of evidence (moderate-quality evidence for reduction in hospital readmissions and low-quality evidence for reduction in mortality). The quality of evidence was high for quality of life and exercise capacity. Pulmonary rehabilitation improves quality of life and exercise capacity and is a safe intervention for patients with COPD after they have experienced an exacerbation. The reasons for diverse effects on hospital readmissions and mortality, however, are not fully clear. Future studies should explore whether the extent of the rehabilitation programme and the organisation of such programmes within specific healthcare systems (e.g. within the rehabilitation setting vs embedded in the continuum of care from hospital to home to outpatient care) determines the effects of rehabilitation after COPD exacerbations.

10.1002/14651858.CD005305.pub4

cochrane-simplification-train-2594

cochrane-simplification-train-2594

We have included seven trials, involving 1396 women. Three trials (1030 women) were good quality. Magnesium sulphate was associated with a reduction in maternal death (seven trials;1396 women; risk ratio (RR) 0.59, 95% confidence interval (CI) 0.38 to 0.92) and recurrence of seizures (seven trials;1390 women; RR 0.43, 95% CI 0.33 to 0.55) compared to diazepam. There were no clear differences in other measures of maternal morbidity. There was no clear difference in perinatal mortality (four trials; 788 infants; RR 1.04, 95% CI 0.81 to 1.34) or neonatal mortality (four trials; 759 infants; RR 1.18, 95% CI 0.75 to 1.84). In the magnesium sulphate group, fewer liveborn babies had an Apgar score less than seven at one minute (two trials; 597 babies; RR 0.75, 95% CI 0.65 to 0.87) or at five minutes (RR 0.70, 95% CI 0.54 to 0.90), and fewer appeared to need intubation at the place of birth (two trials; 591 infants; RR 0.67, 95% CI 0.45 to 1.00). There was no difference in admission to a special care nursery (four trials; 834 infants; RR 0.91, 95% CI 0.79 to 1.05), but fewer babies in the magnesium sulphate group had a length of stay more than seven days (three trials 631 babies; RR 0.66, 95% CI 0.46 to 0.96). Magnesium sulphate for women with eclampsia reduces the risk ratio of maternal death and of recurrence of seizures, compared with diazepam.

Our review of seven randomised trials, involving 1396 women, found that intravenous or intramuscular magnesium sulphate was substantially better than intravenous diazepam in reducing the risk of maternal death and of having further seizures. Treatment was for 24 hours unless there was an indication to continue for longer. Diazepam infusion was titrated against the level of sedation, with the aim of keeping the woman drowsy but rousable.  Use of magnesium sulphate requires monitoring of respiration rate, tendon reflexes and urine output to avoid adverse effects. Fewer babies had low Apgar scores at birth with magnesium sulphate than with diazepam and, although admissions to a special care nursery were similar, fewer babies in the magnesium sulphate group had a length of stay of more than seven days. In other Cochrane reviews, magnesium sulphate was also substantially better than other drugs (phenytoin and lytic cocktail).

10.1002/14651858.CD000127.pub2

cochrane-simplification-train-2595

cochrane-simplification-train-2595

We found three studies for inclusion in the review. One recruited males with a biopsy-proven diagnosis of non-metastatic prostate cancer who were not receiving chemotherapy and had elected to receive external-beam radiation therapy; the second study recruited community-living participants who were aged 55 years and older; the third study recruited university students. These studies included subgroups with anxiety and depression as defined by symptom scores and provided data separately for those subgroups. As this included only 25 people with anxiety and 17 with depression and 20 more with either anxiety or depression, but which was not specified, the results could only be reported narratively. They show no evidence that Reiki is either beneficial or harmful in this population. The risk of bias for the included studies was generally rated as unclear or high for most domains, which reduces the certainty of the evidence. There is insufficient evidence to say whether or not Reiki is useful for people over 16 years of age with anxiety or depression or both.

We found three studies for inclusion in the review. One recruited males with a biopsy-proven diagnosis of prostate cancer who were not receiving chemotherapy and had elected to receive external-beam radiation therapy; the second study recruited community-living participants who were aged 55 years and older; the third study recruited university students.These studies included people with anxiety or depression or both, and reported their results separately. This included only 25 people with anxiety, 17 with depression and 20 more with either anxiety or depression but which was not specified. The search is up to date as of 4 November 2014. Very few people with anxiety or depression or both have been included in randomised studies. This means there is insufficient evidence to make any comment about the usefulness of Reiki for the treatment of anxiety and depression. At best, the quality of the evidence is moderate which, on top of a dearth of evidence, weakens the findings further.

10.1002/14651858.CD006833.pub2

cochrane-simplification-train-2596

cochrane-simplification-train-2596

We included 40 trials with 3694 participants randomized to an exercise (n = 1927) or comparison (n = 1764) group. Cancer diagnoses in study participants included breast, colorectal, head and neck, lymphoma, and other. Thirty trials were conducted among participants who had completed active treatment for their primary or recurrent cancer and 10 trials included participants both during and post cancer treatment. Mode of the exercise intervention included strength training, resistance training, walking, cycling, yoga, Qigong, or Tai Chi. HRQoL and its domains were measured using a wide range of measures. The results suggested that exercise compared with control has a positive impact on HRQoL and certain HRQoL domains. Exercise resulted in improvement in: global HRQoL at 12 weeks' (SMD 0.48; 95% confidence interval (CI) 0.16 to 0.81) and 6 months' (0.46; 95% CI 0.09 to 0.84) follow-up, breast cancer concerns between 12 weeks' and 6 months' follow-up (SMD 0.99; 95% CI 0.41 to 1.57), body image/self-esteem when assessed using the Rosenberg Self-Esteem scale at 12 weeks (MD 4.50; 95% CI 3.40 to 5.60) and between 12 weeks' and 6 months' (mean difference (MD) 2.70; 95% CI 0.73 to 4.67) follow-up, emotional well-being at 12 weeks' follow-up (SMD 0.33; 95% CI 0.05 to 0.61), sexuality at 6 months' follow-up (SMD 0.40; 95% CI 0.11 to 0.68), sleep disturbance when comparing follow-up values by comparison group at 12 weeks' follow-up (SMD -0.46; 95% CI -0.72 to -0.20), and social functioning at 12 weeks' (SMD 0.45; 95% CI 0.02 to 0.87) and 6 months' (SMD 0.49; 95% CI 0.11 to 0.87) follow-up. Further, exercise interventions resulted in decreased anxiety at 12 weeks' follow-up (SMD -0.26; 95% CI -0.07 to -0.44), fatigue at 12 weeks' (SMD -0.82; 95% CI -1.50 to -0.14) and between 12 weeks' and 6 months' (SMD -0.42; 95% CI -0.02 to -0.83) follow-up, and pain at 12 weeks' follow-up (SMD -0.29; 95% CI -0.55 to -0.04) when comparing follow-up values by comparison group. Positive trends and impact of exercise intervention existed for depression and body image (when analyzing combined instruments); however, because few studies measured these outcomes the robustness of findings is uncertain. No conclusions can be drawn regarding the effects of exercise interventions on HRQoL domains of cognitive function, physical functioning, general health perspective, role function, and spirituality. Results of the review need to be interpreted cautiously owing to the risk of bias. All the trials reviewed were at high risk for performance bias. In addition, the majority of trials were at high risk for detection, attrition, and selection bias. This systematic review indicates that exercise may have beneficial effects on HRQoL and certain HRQoL domains including cancer-specific concerns (e.g. breast cancer), body image/self-esteem, emotional well-being, sexuality, sleep disturbance, social functioning, anxiety, fatigue, and pain at varying follow-up periods. The positive results must be interpreted cautiously due to the heterogeneity of exercise programs tested and measures used to assess HRQoL and HRQoL domains, and the risk of bias in many trials. Further research is required to investigate how to sustain positive effects of exercise over time and to determine essential attributes of exercise (mode, intensity, frequency, duration, timing) by cancer type and cancer treatment for optimal effects on HRQoL and its domains.

Cancer survivors often have many psychological and physical adverse events as a result of the cancer and treatment for it. They also suffer from poorer quality of life (QoL) than people without cancer. Some studies have suggested that exercise may be helpful in reducing negative outcomes and improving the QoL of people who have finished cancer treatment. Also, a better QoL may predict longer life. This review looked at the effect of exercise on QoL and areas of life that make up QoL (e.g. tiredness, anxiety, emotional health) among people who had finished all cancer treatment. The review included 40 trials with a total of 3694 people. The results suggest that exercise may improve overall QoL right after the exercise program is completed. Exercise may also reduce the person's worry about his or her cancer, and affect the way the person views his or her body.  Exercise may also help the way the person deals with emotions, sexuality, sleep problems, or functions in society.  Exercise also reduced anxiety, tiredness, and pain at different times during and after the exercise program.  No effect of exercise was found on the person’s ability to think clearly or his or her role function in society.  Also, no effect of exercise was found on the way the person views his or her spiritual or physical health, or physical ability. However, these findings need to be viewed with caution because this review looked at many different kinds of exercise programs, which varied by type of exercise, length of the program, and how hard the trial participants had to exercise. Also, the investigators used a number of different ways to measure QoL. More research is needed to see how to maintain the effects of exercise over a longer period of time after the exercise program is completed, and to determine which parts of the exercise program are necessary (i.e. when to start the program, type of exercise, length of program or exercise session, how hard to exercise). It is also important to find out if one type of exercise is better for a specific cancer type than another for the maximum effect on QoL.

10.1002/14651858.CD007566.pub2

cochrane-simplification-train-2597

cochrane-simplification-train-2597

We included four studies of 12 to 52 weeks' duration, involving 3798 participants with COPD. Mean age of participants ranged from 60.1 to 64.6 years; most were males with baseline mean smoking pack-years of 39.2 to 52.3. They had moderate to severe COPD and baseline mean post-bronchodilator forced expiratory volume in one second (FEV1) ranging from 44.5% to 55.1% of predicted normal. As all studies were systematically conducted according to prespecified protocols, we assessed risk of selection, performance, detection, attrition, and reporting biases as low. Compared with those given placebo, participants in the umeclidinium group had a lesser likelihood of developing moderate exacerbations requiring a short course of steroids, antibiotics, or both (odds ratio (OR) 0.61, 95% confidence interval (CI) 0.46 to 0.80; four studies, N = 1922; GRADE: high), but not specifically requiring hospitalisations due to severe exacerbations (OR 0.86, 95% CI 0.25 to 2.92; four studies, N = 1922, GRADE: low). The number needed to treat for an additional beneficial outcome (NNTB) to prevent an acute exacerbation requiring steroids, antibiotics, or both was 18 (95% CI 13 to 37). Quality of life was better in the umeclidinium group (mean difference (MD) -4.79, 95% CI -8.84 to -0.75; three studies, N = 1119), and these participants had a significantly higher chance of achieving a minimal clinically important difference of at least four units in St George's Respiratory Questionnaire (SGRQ) total score compared with those in the placebo group (OR 1.45, 95% CI 1.16 to 1.82; three studies, N = 1397; GRADE: moderate). The NNTB to achieve one person with a clinically meaningful improvement was 11 (95% CI 7 to 29). The likelihood of all-cause mortality, non-fatal serious adverse events (OR 1.33; 95% CI 0.89 to 2.00; four studies, N = 1922, GRADE: moderate), and adverse events (OR 1.06, 95% CI 0.85 to 1.31; four studies, N = 1922; GRADE: moderate) did not differ between umeclidinium and placebo groups. The umeclidinium group demonstrated significantly greater improvement in change from baseline in trough FEV1 compared with the placebo group (MD 0.14, 95% CI 0.12 to 0.17; four studies, N = 1381; GRADE: high). Symptomatic improvement was more likely in the umeclidinium group than in the placebo group, as determined by Transitional Dyspnoea Index (TDI) focal score (MD 0.76, 95% CI 0.43 to 1.09; three studies, N = 1193), and the chance of achieving a minimal clinically important difference of at least one unit improvement was significantly higher with umeclidinium than with placebo (OR 1.71, 95% CI 1.37 to 2.15; three studies, N = 1141; GRADE: high). The NNTB to attain one person with clinically important symptomatic improvement was 8 (95% CI 5 to 14). The likelihood of rescue medication usage (change from baseline in the number of puffs per day) was significantly less for the umeclidinium group than for the placebo group (MD -0.45, 95% CI -0.76 to -0.14; four studies, N = 1531). Umeclidinium reduced acute exacerbations requiring steroids, antibiotics, or both, although no evidence suggests that it decreased the risk of hospital admission due to exacerbations. Moreover, umeclidinium demonstrated significant improvement in quality of life, lung function, and symptoms, along with lesser use of rescue medications. Studies reported no differences in adverse events, non-fatal serious adverse events, or mortality between umeclidinium and placebo groups; however, larger studies would yield a more precise estimate for these outcomes.

We included four studies involving 3798 people with COPD. Most were men in their 60s who were moderate to heavy smokers. When they started treatment, they had moderate to severe symptoms of COPD. Studies ranged from three months to one year long. Studies were well designed and were funded by the drug manufacturer. Neither people in the study nor people doing the research knew which treatment participants were getting. People in the studies took either umeclidinium or placebo through an inhaler each morning. The conclusions of this review are current to April 2017. We determined the number of people who had a moderate flare-up. A moderate flare-up is treated with short-term oral steroids or antibiotics, or both. People who took umeclidinium were less likely than those given placebo to have a moderate flare-up. Eighteen people with COPD would need to be treated with umeclidinium to prevent one of these flare-ups. People taking umeclidinium probably had a better quality of life, and their lung function was better. People taking umeclidinium were less breathless and took fewer puffs of their reliever inhaler. Results showed little or no difference with umeclidinium in other outcomes, such as risk of dying during the study period, side effects, or the need to be admitted to hospital because of severe flare-ups. We are confident that umeclidinium inhalers are more likely than dummy inhalers to reduce moderate flare-ups and improve symptoms and lung function. However, we are less certain about effects of umeclidinium on quality of life, side effects, and serious side effects. We have limited confidence in terms of hospital admissions due to flare-ups, but this was a rare event. In people with COPD, umeclidinium inhalers improve symptoms, lung function, and quality of life compared with dummy inhalers. They also reduce the use of quick-relief medications and decrease flare-ups that need additional medication. However, no convincing evidence indicates that umeclidinium is better than dummy inhalers in terms of hospitalisations, side effects, serious side effects, or deaths.

10.1002/14651858.CD011897.pub2

cochrane-simplification-train-2598

cochrane-simplification-train-2598

Five randomised controlled trials were identified, of which two satisfied the inclusion criteria. The trials were of poor methodological quality. As a result, it was difficult to have confidence in the individual results and it was not appropriate to pool the data. One trial reported no difference in mortality, number of surgeries or length of stay between the control and HBOT groups once these variables were adjusted for the patients' condition. The second trial reported mean healing times that were shorter in patients exposed to HBOT (mean: 19.7 days versus 43.8 days). No further eligible trials were found when the search was updated in June 2009. This systematic review has not found sufficient evidence to support or refute the effectiveness of HBOT for the management of thermal burns. Evidence from the two randomised controlled trials is insufficient to provide clear guidelines for practice. Further research is needed to better define the role of HBOT in the treatment of thermal burns.

The review found only two randomised trials, with only a limited number of patients. There was no consistent benefit from HBOT, but one trial did suggest an improvement in healing time. Overall, there is little evidence to support or refute the use of HBOT for burns patients. More research is needed.

10.1002/14651858.CD004727.pub2

cochrane-simplification-train-2599

cochrane-simplification-train-2599

Two RCTs and one prospective non-randomised study evaluating pharmacological interventions met the inclusion criteria for this review. As each study evaluated a different drug or intervention using different endpoints, a meta-analysis was not possible. There were no trials of non-pharmacological interventions that met the inclusion criteria. A very small randomised, double-blind, placebo-controlled trial of bevacizumab versus placebo reported that 100% (7/7) of participants on bevacizumab had reduction in brain oedema by at least 25% and reduction in post-gadolinium enhancement, whereas all those receiving placebo had clinical or radiological worsening or both. This was an encouraging finding but due to the small sample size we did not report a relative effect. The authors also failed to provide adequate details regarding the randomisation and blinding procedures Therefore, the certainty of this evidence is low and a larger RCT adhering to reporting standards is needed. An open-label RCT demonstrated a greater reduction in brain oedema (T2 hyperintensity) in the edaravone plus corticosteroid group than in the corticosteroid alone group (MD was 3.03 (95% CI 0.14 to 5.92; low-certainty evidence due to high risk of bias and imprecision); although the result approached borderline significance, there was no evidence of any important difference in the reduction in post-gadolinium enhancement between arms (MD = 0.47, 95% CI - 0.80 to 1.74; low-certainty evidence due to high risk of bias and imprecision). In the RCT of bevacizumab versus placebo, all seven participants receiving bevacizumab were reported to have neurological improvement, whereas five of seven participants on placebo had neurological worsening (very low-certainty evidence due to small sample size and concerns over validity of analyses). While no adverse events were noted with placebo, three severe adverse events were noted with bevacizumab, which included aspiration pneumonia, pulmonary embolus and superior sagittal sinus thrombosis. In the RCT of corticosteroids with or without edaravone, the participants who received the combination treatment were noted to have significantly greater clinical improvement than corticosteroids alone based on LENT/SOMA scale (OR = 2.51, 95% CI 1.26 to 5.01; low-certainty evidence due to open-label design). No differences in treatment toxicities were observed between arms. One included prospective non-randomised study of alpha-tocopherol (vitamin E) versus no active treatment was found but it did not include any radiological assessment. As only one included study was a double-blinded randomised controlled trial, the other studies were prone to selection and detection biases. None of the included studies reported quality of life outcomes or adequately reported details about corticosteroid requirements. A limited number of prospective studies were identified but subsequently excluded as these studies had a limited number of participants evaluating different pharmacological interventions using variable endpoints. There is a lack of good certainty evidence to help quantify the risks and benefits of interventions for the treatment of brain radionecrosis after radiotherapy or radiosurgery. In an RCT of 14 patients, bevacizumab showed radiological response which was associated with minimal improvement in cognition or symptom severity. Although it was a randomised trial by design, the small sample size limits the quality of data. A trial of edaravone plus corticosteroids versus corticosteroids alone reported greater reduction in the surrounding oedema with combination treatment but no effect on the enhancing radionecrosis lesion. Due to the open-label design and wide confidence intervals in the results, the quality of this data was also low. There was no evidence to support any non-pharmacological interventions for the treatment of radionecrosis. Further prospective randomised studies of pharmacological and non-pharmacological interventions are needed to generate stronger evidence. Two ongoing RCTs, one evaluating bevacizumab and one evaluating hyperbaric oxygen therapy were identified.

In October 2017, we searched a list of literature databases and conference proceedings to identify studies that evaluated treatments for brain radionecrosis. A total of three studies were identified that evaluated drugs of which only two were RCTs and one of these RCTs had only 14 participants. No studies evaluating non-drug treatments were identified. The two drugs compared to corticosteroids alone in this review were bevacizumab (a drug affecting the blood vessels) and edaravone (a powerful antioxidant). A very small-sized study reported that bevacizumab improved the appearance of the radionecrosis on magnetic resonance imaging (MRI). This was associated with improvement in neurological symptoms than placebo but also with severe side effects. Edaravone in combination with corticosteroids improved the appearance of radionecrosis on MRI; this was associated with improvement in the reported symptoms using the LENT/SOMA scale. However, the patient and treating team were aware of the particular treatment the patient was receiving, so the reported symptoms may have been influenced by this. None of the included studies reported quality of life outcomes or adequately reported details about corticosteroid requirements. Finally a two arm non-randomised study of vitamin E versus no active treatment based on patient preference reported improvement in learning and memory, but this study did not report any imaging response. The results may have been influenced as patients chose their study treatment thus introducing other potential biases. Based on the findings of this review the certainty of the available evidence is low/very low, which limits our ability to help determine the risks and benefits of the evaluated treatments for brain radionecrosis. The studies were at risk of bias due to aspects of their study designs and/or very limited number of participants. There is a great need for higher-quality evidence with larger multi-centre randomised control trials of treatments for brain radionecrosis. In our search of the literature for this review, two ongoing RCTs, one evaluating bevacizumab and one evaluating hyperbaric oxygen therapy were identified.

10.1002/14651858.CD011492.pub2