GEM/cochrane-simplification huggingface dataset:
Abstract: Heparinization of the infusate decreases the incidence of catheter occlusion but does not affect the frequency of aortic thrombosis. Heparinization of the flush solution is not an adequate alternative.  There does not appear to be an effect on frequency of intraventricular hemorrhage, death or clinical ischemic phenomena. Heparinization of the fluid infused through an umbilical arterial catheter decreases the likelihood of umbilical arterial catheters occluding. The lowest concentration tested so far (0.25 units/mL) has been shown to be effective. Heparinization of flushes without heparinizing the infusate is ineffective. The frequency of aortic thrombosis has not been shown to be affected; however, the confidence intervals for this effect are very wide. The frequency of intraventricular hemorrhage has not been shown to be affected by heparinization of the infusate, but again the confidence intervals are very wide and even a major increase in the incidence of grade 3 and 4 intraventricular hemorrhage would not have been detected.

Plain-language summary: This review found that low heparin doses are effective in preventing catheters becoming blocked and needing to be re-inserted. There is not enough evidence to rule out the possibility of adverse effects. Heparin does not seem to lower the rate of blood clots in the major artery.
Abstract: The initial search identified 1014 records which identified 13 publications for further examination. After screening the full text of the 13 selected papers, only one study evaluating 47 babies finally met the inclusion criteria. Using the same cohort at two different time periods, the study investigated the effects of high versus low dose thyroid hormone replacement in relation to (1) time taken to achieve euthyroid status and (2) neurodevelopmental outcome. The study reported that a high dose is more effective in rising serum thyroxine and free thyroxine concentrations to the target range and earlier normalisation of thyroid stimulating hormone compared to a lower dose. Similarly, full scale intelligence quotient was noted to be significantly higher in children who received the high dose compared to the lower dose. However, the verbal intelligence quotient and performance intelligence quotient were similar in both groups. Growth and adverse effects were not reported in the included trial. There is currently only one randomised controlled trial evaluating the effects of high versus low dose of initial thyroid hormone replacement for CHT. There is inadequate evidence to suggest that a high dose is more beneficial compared to a low dose initial thyroid hormone replacement in the treatment of CHT.

Plain-language summary: There is currently only one study reporting on 47 babies that fulfils our review criteria and compares different high dose versus low dose of initial replacement thyroxine for the treatment of congenital hypothyroidism. There is not enough evidence to suggest that a high dose is more beneficial than a low dose therapy. Growth and adverse effects were not reported in the included study. There should be more randomised controlled trials to assess the effects of high versus low dose of initial thyroid hormone replacement for congenital hypothyroidism.
Abstract: Seven studies enrolling 385 patients were included. There were substantial methodological concerns for most studies including the use of quasi-random allocation methods and sizeable, largely unexplained differences in reported numbers allocated to each group. One study reported phenobarbitone compared to supportive care alone did not reduce treatment failure or time to regain birthweight, but resulted in a significant reduction in duration of supportive care (MD -162.1 min/day, 95% CI -249.2, -75.1). Comparing phenobarbitone to diazepam, meta-analysis of two studies found phenobarbitone resulted in a significant reduction in treatment failure (typical RR 0.39, 95% CI 0.24, 0.62). Comparing phenobarbitone with chlorpromazine, one study reported no significant difference in treatment failure. In infants treated with an opiate, one study reported addition of clonidine resulted in no significant difference in treatment failure, seizures or mortality. In infants treated with an opiate, one study reported addition of phenobarbitone significantly reduced the proportion of time infants had a high abstinence severity score, duration of hospitalisation and maximal daily dose of opiate. Infants with NAS due to opiate withdrawal should receive initial treatment with an opiate. Where a sedative is used, phenobarbitone should be used in preference to diazepam. In infants treated with an opiate, the addition of phenobarbitone or clonidine may reduce withdrawal severity. Further studies are needed to determine the role of sedatives in infants with NAS due to opiate withdrawal and the safety and efficacy of adding phenobarbitone or clonidine in infants treated with an opiate for NAS.

Plain-language summary: Trials of sedatives have generally been of poor quality. Individual studies have reported that use of phenobarbitone compared to supportive care alone reduces the amount time an infant needs supportive care, is better than diazepam at preventing treatment failure and reduces the severity of withdrawal in infants treated with a opiate. In infants treated with an opiate, the addition of a sedative (phenobarbitone or clonidine) may reduce withdrawal severity, although safety and efficacy need confirming. The long term effects of use of phenobarbitone on an infant's development have not been determined.
Abstract: We found one eligible trial that included 72 preterm infants. This trial was not blinded. We are uncertain as to the effect of re-feeding gastric residual on efficacy outcomes such as time to regain birth weight (mean difference (MD) 0.40 days, 95% confidence interval (CI) -2.89 to 3.69 days; very low quality evidence), time to reach enteral feeds ≥ 120 mL/kg/d (MD -1.30 days, 95% CI -2.93 to 0.33 days; very low quality evidence), number of infants with extrauterine growth restriction at discharge (risk ratio (RR) 1.29, 95% CI 0.38 to 4.34; very low quality evidence), duration of total parenteral nutrition (MD -0.30 days, 95% CI -2.07 to 1.47 days; very low quality evidence), and length of hospital stay (MD -1.90 days, 95% CI -25.27 to 21.47 days; very low quality evidence). Similarly, we are uncertain as to the effect of re-feeding gastric residual on safety outcomes such as incidence of stage 2 or 3 necrotising enterocolitis and/or spontaneous intestinal perforation (RR 0.71, 95% CI 0.25 to 2.04; very low quality evidence), number of episodes of feed interruption lasting ≥ 12 hours (RR 0.80, 95% CI 0.42 to 1.52; very low quality evidence), or mortality before discharge (RR 0.50, 95% CI 0.14 to 1.85; low-quality evidence). We are uncertain as to the effect of re-feeding gastric residual in the subgroups of human milk-fed and formula-fed infants. We found no data on other outcomes such as linear and head growth during hospital stay, postdischarge growth, number of infants with parenteral nutrition-associated liver disease, and neurodevelopmental outcomes. We found only limited data from one small unblinded trial on the efficacy and safety of re-feeding gastric residuals in preterm infants. The quality of evidence was low to very low. Hence, available evidence is insufficient to support or refute re-feeding of gastric residuals in preterm infants. A large, randomised controlled trial is needed to provide data of sufficient quality and precision to inform policy and practice.

Plain-language summary: The thorough literature search is up-to-date as of Febraury 2018. We found only one small randomised controlled trial (with 72 preterm infant participants) that addressed this question. We are uncertain as to whether re-feeding stomach aspirates has an effect on important outcomes such as incidence of necrotising enterocolitis, mortality before discharge, time to regain birth weight, time to reach full enteral feeds, duration of parenteral nutrition and duration of hospital stay. Available evidence is insufficient to support or refute re-feeding of stomach aspirates in preterm infants. More trials are needed to examine whether re-feeding the stomach aspirates is beneficial or harmful in preterm infants.
Abstract: Twenty six trials met inclusion criteria. Methodological quality was variable and trial populations were generally small (median sample size = 48, range 14 to 180). Exercise was demonstrated to be effective in terms of short term recovery in rotator cuff disease (RR 7.74 (1.97, 30.32), and longer term benefit with respect to function (RR 2.45 (1.24, 4.86). Combining mobilisation with exercise resulted in additional benefit when compared to exercise alone for rotator cuff disease. Laser therapy was demonstrated to be more effective than placebo for adhesive capsulitis (RR 8, 95%CI 2.11 to 30.34) but not for supraspinatus tendinitis (RR 2, 95%CI 0.98 to 4.09). Both ultrasound and pulsed electromagnetic field therapy resulted in improvement compared to placebo in pain in calcific tendinitis (RR 1.81 (1.26, 2.60) and RR 19 (1.16, 12.43) respectively). There is no evidence of the effect of ultrasound in shoulder pain (mixed diagnosis), adhesive capsulitis or rotator cuff tendinitis. When compared to exercises, ultrasound is of no additional benefit over and above exercise alone. There is some evidence that for rotator cuff disease, corticosteroid injections are superior to physiotherapy and no evidence that physiotherapy alone is of benefit for adhesive capsulitis The small sample sizes, variable methodological quality and heterogeneity in terms of population studied, physiotherapy intervention employed and length of follow up of randomised controlled trials of physiotherapy interventions results in little overall evidence to guide treatment. There is evidence to support the use of some interventions in specific and circumscribed cases. There is a need for trials of physiotherapy interventions for specific clinical conditions associated with shoulder pain, for shoulder pain where combinations of physiotherapy interventions, as well as, physiotherapy interventions as an adjunct to other, non physiotherapy interventions are compared. This is more reflective of current clinical practice. Trials should be adequately powered and address key methodological criteria such as allocation concealment and blinding of outcome assessor.

Plain-language summary: Twenty-six trials presented sufficient data to be included in meta-analysis. There is some evidence from methodologically weak trials to indicate that some physiotherapy interventions are effective for some specific shoulder disorders. The results overall provide little evidence to guide treatment. There is a clear need for further high quality trials of physiotherapy interventions, including trials using combinations of modalities, in the treatment of shoulder disorders.
Abstract: We include three new studies in this update, making a total of 11 included trials with 1387 participants. The average age was 69 years and all trials included men and women. Participants were followed for up to two years. There was an improvement in primary duplex patency at six and 12 months in participants treated with PTA plus stent over lesions treated with PTA alone (six months: odds ratio (OR) 2.90, 95% confidence interval (CI) 1.17 to 7.18, P = 0.02, six studies, 578 participants; 12 months: OR 1.78, 95% CI 1.02 to 3.10, P = 0.04, nine studies, 858 participants). This was lost by 24 months (P = 0.06). There was a significant angiographic patency benefit at six months (OR 2.49, 95% CI 1.49 to 4.17, P = 0.0005, four studies, 329 participants) which was lost by 12 months (OR 1.30, 95% CI 0.84 to 2.00, P = 0.24, five studies, 384 participants). Ankle brachial index (ABI) and treadmill walking distance showed no improvement at 12 months (P = 0.49 and P = 0.57 respectively) between participants treated with PTA alone or PTA with stent insertion. Three trials (660 participants) reported quality of life, which showed no significant difference between participants treated with PTA alone or PTA with stent insertion at any time interval. Antiplatelet therapy protocols and inclusion criteria regarding affected arteries between trials showed marked heterogeneity. Although there was a short-term gain in primary patency there was no sustained benefit from primary stenting of lesions of the superficial femoral artery in addition to angioplasty. Future trials should focus on quality of life for claudication and limb salvage for critical ischaemia.

Plain-language summary: We identified 11 randomised controlled trials with a total of 1387 participants. Their average age was 69 years and all trials included men and women. The participants were randomised to have either balloon angioplasty alone or balloon angioplasty with stent placement. At two years, blood flowing through the narrowing in the arteries was no greater in participants with a stent inserted than in those without. There was a small improvement in the distance that the participants with a stent could walk up to one year later. However, when asked about their quality of life there was no improvement, whether a stent was placed or not, up to one year later. There were differences in the included trials; in some trials people with narrowings in other leg arteries were included. There were also differences between trials in the blood thinning drugs given after stent placement, which may change results, as these agents are important in keeping stents working in other parts of the body. These factors led us to the conclusion that there is a small benefit to adding a stent when performing balloon angioplasty for people in whom balloon angioplasty fails. However, there is insufficient evidence to support this approach as routine practice for everyone and future trials should examine whether subgroups of patients may benefit from stenting.
Abstract: We included seven trials with 1521 participants in this review. The expectant-care group was more likely to have an incomplete miscarriage by two weeks (RR 3.98; 95% CI 2.94 to 5.38) or by six to eight weeks (RR 2.56; 95% CI 1.15 to 5.69). The need for unplanned surgical treatment was greater for the expectant-care group (RR 7.35; 95% CI 5.04 to 10.72). The mean percentage needing surgical management in the expectant-care group was 28%, while 4% of the surgical-treatment group needed additional surgery. The expectant-care group had more days of bleeding (MD 1.59; 95% CI 0.74 to 2.45). Further, more of the expectant-care group needed transfusion (RR 6.45; 95% CI 1.21 to 34.42). The mean percentage needing blood transfusion was 1.4% for expectant care compared with none for surgical management. Results were mixed for pain. Diagnosis of infection was similar for the two groups (RR 0.63; 95% CI 0.36 to 1.12), as were results for various psychological outcomes. Pregnancy data were limited. Costs were lower for the expectant-care group (MD -499.10; 95% CI -613.04 to -385.16; in UK pounds sterling). Expectant management led to a higher risk of incomplete miscarriage, need for unplanned (or additional) surgical emptying of the uterus, bleeding and need for transfusion. Risk of infection and psychological outcomes were similar for both groups. Costs were lower for expectant management. Given the lack of clear superiority of either approach, the woman's preference should be important in decision making. Pharmacological ('medical') management has added choices for women and their clinicians and has been examined in other reviews.

Plain-language summary: We searched for randomized trials that compared waiting versus surgery for miscarriage. In addition, we looked at reference lists to find trials. We also wrote to researchers to find more studies. Seven trials with 1521 women looked at waiting versus surgery for miscarriage. More women who waited for the miscarriage to complete on its own had tissue left in the womb. This was studied at two weeks and at six to eight weeks. More of these women needed surgery to complete the process. These women also had more days of bleeding. Some needed to be given blood, compared with none in the surgery group. Both groups had about the same numbers of infections. Results were mixed for pain. Mental health also seemed about the same for both treatment groups. Costs were lower for waiting than for surgery. Overall, no strong medical results argue for either approach. Information was limited on future pregnancy. One trial was large, while the others had small numbers of women. What the woman prefers should be the major concern. Drug treatment (such as with misoprostol and mifepristone) has added choices for women and their clinicians, and has been studied in other reviews.
Abstract: The review included three studies involving 112 participants. All the included studies performed the comparison breathing exercises as part of a more complex intervention versus control. There were no trials comparing breathing exercises alone with control. Asthma severity of participants from the included studies varied. The studies measured: quality of life, asthma symptoms, reduction in medication usage, number of acute exacerbations and lung function. Breathing exercise techniques used by the included studies consisted of lateral costal breathing, diaphragmatic breathing, inspiratory patterns and pursed lips. One study included in the review did not specify the type of breathing exercise used. The control groups received different interventions: one received placebo treatment, one an educational programme and doctor appointments, and one was not described. There were no reported between-group comparisons for any of the primary outcomes. We judged the included studies as having an unclear risk of bias. We could draw no reliable conclusions concerning the use of breathing exercises for children with asthma in clinical practice. The breathing exercises were part of a more comprehensive package of care, and could not be assessed on their own. Moreover, there were methodological differences among the three small included studies and poor reporting of methodological aspects and results in most of the included studies.

Plain-language summary: The included studies had an overall small number of participants and sessions. No included study compared breathing exercises alone versus a control. Instead, breathing exercises were part of a package of treatments and were compared to a control. The methods used to conduct the studies were not as well reported as we would like and so were unclear about the quality of the trials. Overall, we judged the included studies as being at an unclear risk of bias and the quality of the evidence included in the review was low. We could draw no reliable conclusions concerning the use of breathing exercises for children with asthma in clinical practice.
Abstract: We obtained and scrutinised 41 potentially relevant records, and from these we could include only six trials (n = 1835). Five of the six trials had high risk of attrition bias and all trials were sponsored by pharmaceutical companies. Results showed a clinically important change in global state (1 RCT, n = 336, RR 0.81, 95% CI 0.68 to 0.97, low-quality evidence) and mental state (1 RCT, n = 336, RR 0.72, 95% CI 0.59 to 0.86, very low-quality evidence) at short-term amongst people receiving asenapine. People receiving asenapine demonstrated significant reductions in negative symptoms (1 RCT, n = 336, MD -1.10, 95% CI -2.29 to 0.09, very low-quality evidence) at short-term. Individuals receiving asenapine demonstrated significantly fewer incidents of serious adverse effects (1 RCT, n = 386, RR 0.29, 95% CI 0.14 to 0.63, very low-quality evidence) at medium-term. There was no clear difference in people discontinuing the study for any reason between asenapine and placebo at short-term (5 RCTs, n = 1046, RR 0.91, 95% CI 0.80 to 1.04, very low-quality evidence). No trial reported data for extrapyramidal symptoms or costs. There is some, albeit preliminary, evidence that asenapine provides an improvement in positive, negative, and depressive symptoms, whilst minimising the risk of adverse effects. However due to the low-quality and limited quantity of evidence, it remains difficult to recommend the use of asenapine for people with schizophrenia. We identify a need for large-scale, longer-term, better-designed and conducted randomised controlled trials investigating the clinical effects and safety of asenapine.

Plain-language summary: The review includes six trials with 1835 people. The trials randomised people with schizophrenia to receive either asenapine or placebo. Five of these trials had high rates of people leaving early and were sponsored by pharmaceutical companies. There is some evidence that asenapine, when compared to placebo, improves the positive, negative and depressive symptoms of schizophrenia while having less risk of debilitating side effects. However, due to the low quantity and limited quality of evidence currently available, it remains difficult to recommend the use of asenapine for schizophrenia. There is a need for large-scale, longer-term follow up, and bias-free randomised controlled trials investigating the effects and safety of asenapine. Ben Gray, Senior Peer Researcher, McPin Foundation. http://mcpin.org/
Abstract: Sixteen placebo controlled trials have been completed with atypical antipsychotics although only nine had sufficient data to contribute to a meta-analysis and only five have been published in full in peer reviewed journals. No trials of amisulpiride, sertindole or zotepine were identified which met the criteria for inclusion.  The included trials led to the following results:  1. There was a significant improvement in aggression with risperidone and olanzapine treatment compared to placebo.  2. There was a significant improvement in psychosis amongst risperidone treated patients.  3. Risperidone and olanzapine treated patients had a significantly higher incidence of serious adverse cerebrovascular events (including stroke), extrapyramidal side effects and other important adverse outcomes.  4. There was a significant increase in drop-outs in risperidone (2 mg) and olanzapine (5-10 mg) treated patients.  5. The data were insufficient to examine impact upon cognitive function. Evidence suggests that risperidone and olanzapine are useful in reducing aggression and risperidone reduces psychosis, but both are associated with serious adverse cerebrovascular events and extrapyramidal symptoms. Despite the modest efficacy, the significant increase in adverse events confirms that neither risperidone nor olanzapine should be used routinely to treat dementia patients with aggression or psychosis unless there is severe distress or risk of physical harm to those living and working with the patient. Although insufficient data were available from the considered trials, a meta-analysis of seventeen placebo controlled trials of atypical neuroleptics for the treatment of behavioural symptoms in people with dementia conducted by the Food and Drug Administration suggested a significant increase in mortality (OR 1.7). A peer-reviewed meta-analysis (Schneider 2005) of 15 placebo controlled studies (nine unpublished) found similarly increased risk in mortality (OR=1.54, 95% CI 0.004 to 0.02, p=0.01) for the atypical neuroleptics.

Plain-language summary: Atypical antipsychotics have become the pharmacological treatment of choice for many clinicians in the treatment of behavioural and psychiatric symptoms in people with dementia, and the largest evidence base for double blind placebo controlled trials in this area is for risperidone. Particularly in view of recent safety concerns, a meta-analysis of efficacy and adverse events to inform clinical practice is timely. Modest efficacy is evident, but the elevated risk of cerebrovascular adverse events, mortality, upper respiratory infections, oedema and extrapyramidal symptoms is a concern, particularly as selective reporting makes interpretation of other potential adverse outcomes impossible.