GEM/cochrane-simplification huggingface dataset:
Abstract: We identified one eligible study that examined the effect of computerised cognitive training (CCT) in 6742 participants over 50 years of age, with training and follow-up duration of six months. We considered the study to be at high risk of attrition bias and the overall quality of the evidence to be low. Researchers provided no data on our primary outcome. Results indicate that there may be a small advantage for the CCT group for executive function (mean difference (MD) -1.57, 95% confidence interval (CI) -1.85 to -1.29; participants = 3994; low-quality evidence) and a very small advantage for the control group for working memory (MD 0.09, 95% CI 0.03 to 0.15; participants = 5831; low-quality evidence). The intervention may have had little or no effect on episodic memory (MD -0.03, 95% CI -0.10 to 0.04; participants = 3090; low-quality evidence). We found low-quality evidence from only one study. We are unable to determine whether computerised cognitive training is effective in maintaining global cognitive function among healthy adults in midlife. We strongly recommend that high-quality studies be undertaken to investigate the effectiveness and acceptability of cognitive training in midlife, using interventions that last long enough that they may have enduring effects on cognitive and brain reserve, and with investigators following up long enough to assess effects on clinically important outcomes in later life.

Plain-language summary: We found that a lot of shorter studies had been conducted, but only one study met our criteria for this review. It took place in the UK and included two different types of online cognitive training. The control group participated in an online game that was not expected to have cognitive effects. This training lasted six months, and study authors measured cognition at the end of the training period. Resarchers randomised 6742 people in the study, but the dropout rate was high. We thought this put the results at high risk of bias; therefore we considered the quality of evidence provided by this study to be low, meaning that further research might well lead to different results. This study did not measure overall cognitive functioning - which we were most interested in - but it did measure some subtypes of cognitive function. The cognitive training group did slightly better on a test of reasoning, and the control group did very slightly better on a test of working memory, which is a very short-term type of memory. No evidence suggested that the groups differed in memory measured by a word-learning test. We were not able to tell whether taking part in computerised cognitive training in midlife has any lasting effects on cognitive function. We think this is an important question that should be investigated further in trials that test cognitive training over three months or longer. It will also be important for researchers to try to find the best ways to keep people motivated to persist with training.
Abstract: We included two studies with a total of 40 participants in the review. Exercise-based CR consisted of aerobic or resistance training or both three times per week for six to eight weeks. Exercise intensity was 50% of oxygen consumption (VO2) reserve, or ranged from 60% to 80% of heart rate reserve. Two serious adverse events were observed in one trial, in which participants did not complete the study due to infections. Furthermore, a total of four participants in each group required visits to the emergency department, although these participants did complete the study. Summary scores from the 36-item Short Form Health Survey (SF-36) and the Kansas City Cardiomyopathy Questionnaire (KCCQ) were measured as quality of life. One trial reported that the KCCQ summary score improved by 14.4 points in the exercise group compared with 0.5 points in the usual care group. The other trial reported that the SF-36 total score improved by 29.2 points in the exercise group compared with 16.3 points in the usual care group. A large difference in quality of life was observed between groups at the end of follow-up (standardised mean difference 0.88, 95% CI -0.12 to 1.88; 37 participants; 2 studies; very low-quality of evidence). However, there was no evidence for the effectiveness of exercise-based CR due to the young age of the participants, high risk of performance bias, very small sample size, and wide confidence intervals, which resulted in very low-quality evidence. Furthermore, we were not able to determine the effect of exercise-based CR on mortality, rehospitalisation, heart transplantation, and cost, as these outcomes were not reported. The evidence is currently inadequate to assess the safety and efficacy of exercise-based CR for people with implantable VADs compared with usual care. The amount of RCT evidence was very limited and of very low quality. In addition, the training duration was very short term, that is from six to eight weeks. Further high-quality and well-reported RCTs of exercise-based CR for people with implantable VADs are needed. Such trials need to collect data on events (mortality and rehospitalisation), patient-related outcomes (including quality of life), and cost-effectiveness.

Plain-language summary: We assessed the quality of the evidence for quality of life as very low due to the young age of the participants, Insufficient blinding, small number of participants, and imprecision because of wide range of confidence intervals. The effects of exercise-based CR for people with implantable VADs were not clear. The current evidence is inadequate to assess the benefits and harms of exercise-based CR for people with implantable VADs compared with usual care. The amount of randomised controlled trial evidence was very limited and of very low quality. In addition, the training duration was very short term. High-quality randomised controlled trials are needed to collect data on events (death and rehospitalisation), patient-related outcomes (including quality of life), and cost.
Abstract: We identified 27 studies (1549 participants) that were eligible for inclusion. These studies provided no data relating to aldosterone antagonists in addition to ACEi or ARB (or both) on patient-level outcomes including major cardiovascular events and mortality and progression to end-stage kidney disease (ESKD) requiring dialysis or transplantation. Compared with ACEi or ARB (or both), non-selective aldosterone antagonists (spironolactone) combined with ACEi or ARB (or both) significantly reduced 24-hour protein excretion (11 studies, 596 participants): SMD -0.61, 95% CI -1.08 to -0.13). There was a significant reduction in both systolic and diastolic blood pressure (BP) at the end of treatment with additional non-selective aldosterone antagonist therapy (systolic BP (10 studies, 556 participants): MD -3.44 mm Hg, 95% CI -5.05 to -1.83) (diastolic BP (9 studies, 520 participants): MD -1.73 mm Hg, 95% CI -2.83 to -0.62). However, we found that aldosterone antagonist treatment had imprecise effects at the end of treatment on GFR (9 studies, 528 participants; MD -2.55 mL/min/1.73 m², 95% CI -5.67 to 0.51), doubled the risk of hyperkalaemia (11 studies, 632 patients): RR 2.00, 95% CI 1.25 to 3.20; number needed to treat for an additional harmful outcome (NNTH): 7.2, 95% CI 3.4 to ∞) and increased the risk of gynaecomastia compared to ACEi or ARB (or both) (4 studies, 281 patients): RR 5.14, 95% CI 1.14 to 23.23; NNTH: 14.1, 95% CI 8.7 to 37.3). Most studies enrolled few patients (range 12 to 268) and were powered to observe differences in surrogate end points rather than patient-focused outcomes. Nine studies had a cross-over design and the majority of studies did not adequately report study methods to assess methods and study quality. Aldosterone antagonists reduced proteinuria and blood pressure in adults who had mild to moderate CKD and were treated with ACEi or ARB (or both), but increase hyperkalaemia and gynaecomastia. Whether adding aldosterone antagonists to ACEi or ARB (or both) reduced the risk of major cardiovascular events or ESKD in this population is unknown.

Plain-language summary: This review of available trials showed that adding aldosterone antagonist treatment to standard therapy reduced protein release into the urine and lowered blood pressure but had uncertain effects on kidney function and survival. Treatment also increases the amount of potassium in the blood which may require treatment changes, extra blood tests and is potentially harmful. Whether aldosterone blockers protect kidney function to lower the chances needing dialysis or kidney transplantation or prevent heart disease in people who have CKD is unclear and not answered by existing research.
Abstract: No trials comparing hydroxyurea with placebo or standard care were found. However, we included one randomised controlled trial (n = 61) comparing 20 mg/kg/day with 10 mg/kg/day of hydroxyurea for 24 weeks. Both haemoglobin and foetal haemoglobin levels were lower at 24 weeks in the 20 mg group compared with the 10 mg group, mean difference -2.39 (95% confidence interval - 2.8 to -1.98) and mean difference -1.5 (95% confidence interval -1.83 to -1.17), respectively. Major adverse effects were significantly more common in the 20 mg group, for neutropenia risk ratio 9.93 (95% confidence interval 1.34 to 73.97) and for thrombocytopenia risk ratio 3.68 (95% confidence interval 1.13 to 12.07). No difference was reported for minor adverse effects (gastrointestinal disturbances and raised liver enzymes). The effect of hydroxyurea on transfusion frequency was not reported. The overall quality for the outcomes reported was graded as very low mainly because the outcomes were derived from only one small study with an unclear method of allocation concealment. There is no evidence from randomised controlled trials to show whether hydroxyurea has any effect compared with controls on the need for blood transfusion. Administration of 10 mg/kg/day compared to 20 mg/kg/day of hydroxyurea resulted in higher haemoglobin levels and seems safer with fewer adverse effects. It has not been reported whether hydroxyurea is capable of reducing the need for blood transfusion. Large well-designed randomised controlled trials with sufficient duration of follow up are recommended.

Plain-language summary: We did not find any randomised controlled trials (where people taking part in the trial have equal chances of being in the treatment or the control group) comparing hydroxyurea with a placebo (a dummy drug) or usual care. However, we found one randomised controlled trial comparing two different doses of hydroxyurea (10 mg/kg/day versus 20 mg/kg/day given for 24 weeks) and included it in this review. A total of 61 people took part in this trial. The lower dose of hydroxyurea appeared to increase levels of foetal haemoglobin, but the higher dose did not. We found some evidence that the higher dose was harmful, particularly to the bone marrow. The trial did not look at whether blood transfusions could be given less often or whether the effects of the anaemia were reduced. In the short term, the lower dose does not appear to have any side effects. The trial duration was very short and we need to know what might happen if treatment with hydroxyurea is continued for a longer period of time. We graded the quality of the evidence as very low. This was because our key results are based on only one small trial. In addition we can not be sure whether the trial methods were of high quality because the authors have not completely described them.
Abstract: While five studies addressed the interventions of interest, we did not include them in the review because the investigators of the studies did not report any information specific to people with cystic fibrosis. Our attempts to obtain this information have not yet been successful. We will include any provided data in future updates of the review. The lack of currently available evidence makes it impossible to draw conclusions about the comparative efficacy and safety of the various immunosuppressive drugs among people with cystic fibrosis after lung transplantation. A 2013 Cochrane Review comparing tacrolimus with cyclosporine in all lung transplant recipients (not restricted to those with cystic fibrosis) reported no significant difference in mortality and risk of acute rejection. However, tacrolimus use was associated with lower risk of broncholitis obliterans syndrome and arterial hypertension and higher risk of diabetes mellitus. It should be noted that this wider review contained only a small number of included studies (n = 3) with a high risk of bias. Additional randomised studies are required to provide evidence for the benefit and safety of the use of immunosuppressive therapy among people with cystic fibrosis after lung transplantation.

Plain-language summary: Although we found five studies which looked at anti-rejection drugs, they included people with a number of chronic conditions and not just cystic fibrosis. The studies we found reported results from all volunteers combined and we were not able to isolate the results that were specific to people with cystic fibrosis. We contacted the researchers who conducted these studies, but they have not yet sent us the specific results we need. If we receive these results, we will include them in the future when we update this systematic review. There is a review of drugs to suppress the immune systems of people who have had lung transplants (not restricted to those with cystic fibrosis) and this only included three studies which the review authors judged to have a high risk of bias. The review did not find that any one drug was better than another for reducing the chances of death or acute rejection; but one drug (tacrolimus) led to a lower risk of long-term rejection and high blood pressure, although there was a higher risk of diabetes. Research is needed on the use of drugs that suppress the immune system in people with cystic fibrosis who have received a lung transplant.
Abstract: Pentoxifylline used as an adjunct to antibiotics in neonates with sepsis decreased all-cause mortality during hospital stay (typical RR 0.57, 95% CI 0.35 to 0.93; typical RD -0.08, 95% CI -0.14 to -0.01; NNTB 13, 95% CI 7 to 100; 6 studies, 416 participants, low-quality evidence). Subgroup analyses revealed decrease in mortality in preterm infants, infants with confirmed sepsis, and infants with gram-negative sepsis (low-quality evidence, four studies). Pentoxifylline decreased length of hospital stay (MD -7.59 days, 95% CI -11.65 to -3.52; 2 studies, 148 participants, low-quality evidence). Pentoxifylline did not change the risk of development of NEC, chronic lung disease, severe intraventricular haemorrhage, retinopathy of prematurity, or periventricular leukomalacia in neonates with sepsis (one to two studies, very low-quality evidence). Pentoxifylline therapy compared to pentoxifylline and immunoglobulin M-enriched intravenous immunoglobulin or immunoglobulin M-enriched intravenous immunoglobulin alone did not change mortality or development of NEC in neonates with sepsis (one study, very low-quality evidence). We noted no adverse effects due to pentoxifylline. We identified no trials evaluating pentoxifylline treatment for NEC. Low-quality evidence from six small studies suggests that pentoxifylline therapy as an adjunct to antibiotics in neonatal sepsis decreases mortality without any adverse effects. We encourage researchers to undertake large, well-designed multicentre trials to confirm or refute the effectiveness of pentoxifylline in reducing mortality and morbidity in neonates with sepsis or NEC.

Plain-language summary: Six randomised controlled trials met our inclusion criteria. We found low-quality evidence that pentoxifylline in combination with antibiotics decreases deaths and duration of hospital stay in newborn sepsis. Pentoxifylline treatment did not affect lung, eye, or brain injury as a result of sepsis (very low-quality evidence). We identified no adverse effects due to pentoxifylline. There were no completed studies looking at pentoxifylline treatment in NEC. We need better-quality evidence on the use of pentoxifylline in the treatment of sepsis or NEC in the newborn.
Abstract: Twelve studies met the inclusion criteria recruiting 350 participants. Trial reporting was poor and trial quality was deemed inadequate to generalise findings. There was variation in the type of active and sham acupuncture, the outcomes measured and time-points presented. The points used in the sham arm of some studies are used for the treatment of asthma according to traditional Chinese medicine. Two studies used individualised treatment strategies and one study used a combination strategy of formula acupuncture with the addition of individualised points. No statistically significant or clinically relevant effects were found for acupuncture compared to sham acupuncture. Data from two small studies were pooled for lung function (post-treatment FEV1): Standardised Mean Difference 0.12, 95% confidence interval -0.31 to 0.55). There is not enough evidence to make recommendations about the value of acupuncture in asthma treatment. Further research needs to consider the complexities and different types of acupuncture.

Plain-language summary: The objective of this review was to assess whether there is evidence from randomised controlled trials that asthma patients benefit from acupuncture. The studies included in the review were of variable quality and had inconsistent results. Future research should concentrate on establishing whether there is a non-specific component of acupuncture which benefits recipients of treatment. There should be an assessment not merely of placebo treatment, but also of 'no treatment' as well. There is insufficient evidence to make recommendations about the value of acupuncture as a treatment for asthma based on current evidence.
Abstract: Nine RCTs with a total of 320 participants were included. Four SSRIs were evaluated: fluoxetine (three studies), fluvoxamine (two studies), fenfluramine (two studies) and citalopram (two studies). Five studies included only children and four studies included only adults. Varying inclusion criteria were used with regard to diagnostic criteria and intelligence quotient of participants. Eighteen different outcome measures were reported. Although more than one study reported data for Clinical Global Impression (CGI) and obsessive-compulsive behaviour (OCB), different tool types or components of these outcomes were used in each study. As such, data were unsuitable for meta-analysis, except for one outcome (proportion improvement). One large, high-quality study in children showed no evidence of positive effect of citalopram. Three small studies in adults showed positive outcomes for CGI and OCB; one study showed improvements in aggression, and another in anxiety. There is no evidence of effect of SSRIs in children and emerging evidence of harm. There is limited evidence of the effectiveness of SSRIs in adults from small studies in which risk of bias is unclear.

Plain-language summary: We found nine trials, involving 320 people, which evaluated four SSRIs: fluoxetine, fluvoxamine, fenfluramine and citalopram. Five studies included only children and four studies included only adults. One trial enrolled 149 children, but the other trials were much smaller. We found no trials that evaluated sertraline, paroxetine or escitalopram. There is no evidence to support the use of SSRIs to treat autism in children. There is limited evidence, which is not yet sufficiently robust, to suggest effectiveness of SSRIs in adults with autism. Treatment with an SSRI may cause side effects. Decisions about the use of SSRIs for established clinical indications that may co-occur with autism, such as obsessive-compulsive disorder and depression in adults or children, and anxiety in adults, should be made on a case-by-case basis.
Abstract: A total of three studies including 242 participants met the inclusion criteria for this review. One study reported the diagnostic performance of CRP for two threshold levels (> 200 mg/L and > 279 mg/L) without stating the day on which the CRP was measured. One study reported the diagnostic performance of procalcitonin on day 1 (1 day after admission) using a threshold level of 0.5 ng/mL. One study reported the diagnostic performance of CRP on day 3 (3 days after admission) using a threshold level of 140 mg/L and LDH on day 5 (5 days after admission) using a threshold level of 290 U/L. The sensitivities and specificities varied: the point estimate of the sensitivities ranged from 0.72 to 0.88, while the point estimate of the specificities ranged from 0.75 to 1.00 for the different index tests on different days of hospital admission. However, the confidence intervals were wide: confidence intervals of sensitivities ranged from 0.51 to 0.97, while those of specificities ranged from 0.18 to 1.00 for the different tests on different days of hospital admission. Overall, none of the tests assessed in this review were sufficiently accurate to suggest that they could be useful in clinical practice. The paucity of data and methodological deficiencies in the studies meant that it was not possible to arrive at any conclusions regarding the diagnostic test accuracy of the index test because of the uncertainty of the results. Further well-designed diagnostic test accuracy studies with prespecified index test thresholds of CRP, procalcitonin, LDH; appropriate follow-up (for at least two weeks to ensure that the person does not have pancreatic necrosis, as early scans may not indicate pancreatic necrosis); and clearly defined reference standards (of surgical or radiological confirmation of pancreatic necrosis) are important to reliably determine the diagnostic accuracy of CRP, procalcitonin, and LDH.

Plain-language summary: We performed a thorough literature search for studies reporting the accuracy of CRP, procalcitonin, or LDH in identifying pancreatic necrosis. We included studies reported until 20 March 2017. We identified three studies reporting information on 242 people with pancreatitis. The studies included pancreatitis due to all causes. Variations in when the studies carried out the blood tests and what level was considered abnormal meant that we were unable to combine the data to provide the overall results. It was not possible to arrive at any firm conclusions about how accurate the tests are for the following reasons. • The studies included few participants. As a result, there was significant uncertainty in the results. • The studies were of poor methodological quality, which introduced additional uncertainty in the results. • For the results to be trusted, they must be reproduced in another group of participants. Since this was not done, there was uncertainty in the results. All of the studies were of unclear or low methodological quality, which may result in arriving at false conclusions.