High Risk Of Attrition Bias Research Articles

Approaches to promote handwashing and sanitation behaviour change in low‐ and middle‐income countries: a mixed method systematic review

Approaches to promote handwashing and sanitation behaviour change in low‐ and middle‐income countries: a mixed method systematic review

E‐learning of evidence‐based health care (EBHC) to increase EBHC competencies in healthcare professionals: a systematic review

Evidence-based health care (EBHC) is decision-making for health care, informed by the best research evidence. Doctors, nurses and allied health professionals need to have the necessary knowledge and skills to apply EBHC. The use of electronic learning (e-learning) for EBHC training is increasing.E-learning, compared to no learning, improves EBHC knowledge and skills but not attitudes and behaviour. There is no difference in outcomes when comparing e-learning to face-to-face learning. Combining e-learning with face-to-face learning (blended learning) has a positive impact on EBHC knowledge, skills, attitude and behaviour.

Antenatal breastfeeding education for increasing breastfeeding duration.

Breastfeeding (BF) is well recognised as the best food for infants. The impact of antenatal BF education on the duration of BF has not been evaluated.To evaluate the effectiveness of antenatal BF education for increasing BF initiation and duration.We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (21 April 2010), CENTRAL (The Cochrane Library 2010, Issue 2), MEDLINE (1966 to April 2010) and SCOPUS (January 1985 to April 2010). We contacted experts and searched reference lists of retrieved articles. We updated the search of the Pregnancy and Childbirth Group's Trials Register on 28 September 2011 and added the results to the awaiting classification section of the review.All identified published, unpublished and ongoing randomised controlled trials (RCTs) assessing the effect of formal antenatal BF education or comparing two different methods of formal antenatal BF education, on duration of BF. We excluded RCTs that also included intrapartum or postpartum BF education.We assessed all potential studies identified as a result of the search strategy. Two review authors extracted data from each included study using the agreed form and assessed risk of bias. We resolved discrepancies through discussion.We included 17 studies with 7131 women in the review and 14 studies involving 6932 women contributed data to the analyses. We did not do any meta-analysis because there was only one study for each comparison.Five studies compared a single method of BF education with routine care. Peer counselling significantly increased BF initiation.Three studies compared one form of BF education versus another. No intervention was significantly more effective than another intervention in increasing initiation or duration of BF.Seven studies compared multiple methods versus a single method of BF education. Combined BF educational interventions were not significantly better than a single intervention in initiating or increasing BF duration. However, in one trial a combined BF education significantly reduced nipple pain and trauma.One study compared different combinations of interventions. There was a marginally significant increase in exclusive BF at six months in women receiving a booklet plus video plus lactation consultation (LC) compared with the booklet plus video only.Two studies compared multiple methods of BF education versus routine care. The combination of BF booklet plus video plus LC was significantly better than routine care for exclusive BF at three months.Because there were significant methodological limitations and the observed effect sizes were small, it is not appropriate to recommend any antenatal BF education.There is an urgent need to conduct RCTs study with adequate power to evaluate the effectiveness of antenatal BF education.

Fibrin glue versus sutures for conjunctival autografting in primary pterygium surgery.

Pterygium, a growth of the conjunctiva over the cornea, is a progressive disease leading in advanced stages to visual impairment, restriction of ocular motility, chronic inflammation and cosmetic concerns. Surgical removal is the treatment of choice, but recurrence can be a problem. Currently the best surgical option in terms of recurrence is conjunctival autograft. To date the most common surgical methods of attaching conjunctival autografts to the sclera are through suturing or fibrin glue. Each method presents its own advantages and disadvantages. Sutures require considerable skill from the surgeon and can be associated with a prolonged operation time, postoperative discomfort and suture-related complications, whereas fibrin glue may give a decreased operation time, improve postoperative comfort and avoid suture-related problems. To assess the effectiveness of fibrin glue compared to sutures in conjunctival autografting for the surgical treatment of pterygium. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2016), Embase (January 1980 to October 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 14 October 2016. We included randomised controlled trials (RCTs) in any setting where fibrin glue was compared with sutures to treat people with pterygium. Two review authors independently screened the search results, assessed trial quality, and extracted data using standard methodological procedures expected by Cochrane. Our primary outcome was recurrence of pterygium defined as any re-growth of tissue from the area of excision across the limbus onto the cornea. The secondary outcomes were surgical time and complication rate. We graded the certainty of the evidence using GRADE. We included 14 RCTs conducted in Brazil, China, Egypt, India, Malaysia, New Zealand, Philippines, Saudi Arabia, Sweden and Turkey. The trials were published between 2004 and 2016, and were assessed as a mixture of unclear and low risk of bias with three studies at high risk of attrition bias. Only adults were enrolled in these studies.Using fibrin glue for the conjunctival autograft may result in less recurrence of pterygium compared with using sutures (risk ratio (RR) 0.47, 95% CI 0.27 to 0.82, 762 eyes, 12 RCTs; low-certainty evidence). If pterygium recurs after approximately 10 in every 100 surgeries with sutures, then using fibrin glue may result in approximately 5 fewer cases of recurrence in every 100 surgeries (95% CI 2 fewer to 7 fewer cases). Using fibrin glue may lead to more complications compared with sutures (RR 1.92; 95% CI 1.22 to 3.02, 11 RCTs, 673 eyes, low-certainty evidence). The most common complications reported were: graft dehiscence, graft retraction and granuloma. On average using fibrin glue may mean that surgery is quicker compared with suturing (mean difference (MD) -17.01 minutes 95% CI -20.56 to -13.46), 9 RCTs, 614 eyes, low-certainty evidence). The meta-analyses, conducted on people with pterygium in a hospital or outpatient setting, show fibrin glue may result in less recurrence and may take less time than sutures for fixing the conjunctival graft in place during pterygium surgery. There was low-certainty evidence to suggest a higher proportion of complications in the fibrin glue group.

Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis.

Interferons-beta (IFNs-beta) and glatiramer acetate (GA) were the first two disease-modifying therapies (DMTs) approved 20 years ago for the treatment of multiple sclerosis (MS). DMTs' prescription rates as first or switching therapies and their costs have both increased substantially over the past decade. As more DMTs become available, the choice of a specific DMT should reflect the risk/benefit profile, as well as the impact on quality of life. As MS cohorts enrolled in different studies can vary significantly, head-to-head trials are considered the best approach for gaining objective reliable data when two different drugs are compared. The purpose of this systematic review is to summarise available evidence on the comparative effectiveness of IFNs-beta and GA on disease course through the analysis of head-to-head trials.This is an update of the Cochrane review 'Interferons-beta versus glatiramer acetate for relapsing-remitting multiple sclerosis' (first published in the Cochrane Library 2014, Issue 7). To assess whether IFNs-beta and GA differ in terms of safety and efficacy in the treatment of people with relapsing-remitting (RR) MS. We searched the Trials Register of the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group (08 August 2016) and the reference lists of retrieved articles. We contacted authors and pharmaceutical companies. Randomised controlled trials (RCTs) comparing directly IFNs-beta versus GA in study participants affected by RRMS. We used standard methodological procedures as expected by Cochrane. Six trials were included and five trials contributed to this review with data. A total of 2904 participants were randomly assigned to IFNs (1704) and GA (1200). The treatment duration was three years for one study, two years for the other four RCTs while one study was stopped early (after one year). The IFNs analysed in comparison with GA were IFN-beta 1b 250 mcg (two trials, 933 participants), IFN-beta 1a 44 mcg (three trials, 466 participants) and IFN-beta 1a 30 mcg (two trials, 305 participants). Enrolled participants were affected by active RRMS. All studies were at high risk for attrition bias. Three trials are still ongoing, one of them completed.Both therapies showed similar clinical efficacy at 24 months, given the primary outcome variables (number of participants with relapse (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.87 to 1.24) or progression (RR 1.11, 95% CI 0.91 to 1.35). However at 36 months, evidence from a single study suggests that relapse rates were higher in the group given IFNs than in the GA group (RR 1.40, 95% CI 1.13 to 1.74, P value 0.002).Secondary magnetic resonance imaging (MRI) outcomes analysis showed that effects on new or enlarging T2- or new contrast-enhancing T1 lesions at 24 months were similar (mean difference (MD) -0.15, 95% CI -0.68 to 0.39, and MD -0.14, 95% CI -0.30 to 0.02, respectively). However, the reduction in T2- and T1-weighted lesion volume was significantly greater in the groups given IFNs than in the GA groups (MD -0.58, 95% CI -0.99 to -0.18, P value 0.004, and MD -0.20, 95% CI -0.33 to -0.07, P value 0.003, respectively).The number of participants who dropped out of the study because of adverse events was similar in the two groups (RR 0.95, 95% CI 0.64 to 1.40).The quality of evidence for primary outcomes was judged as moderate for clinical end points, but for safety and some MRI outcomes (number of active T2 lesions), quality was judged as low. The effects of IFNs-beta and GA in the treatment of people with RRMS, including clinical (e.g. people with relapse, risk to progression) and MRI (Gd-enhancing lesions) measures, seem to be similar or to show only small differences. When MRI lesion load accrual is considered, the effect of the two treatments differs, in that IFNs-beta were found to limit the increase in lesion burden as compared with GA. Evidence was insufficient for a comparison of the effects of the two treatments on patient-reported outcomes, such as quality-of-life measures.

Pancreatic enzyme replacement therapy for people with cystic fibrosis.

Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review. To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 15 July 2016.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 22 July 2016. Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. One parallel trial and 12 cross-over trials of children and adults with cystic fibrosis were included in the review. The number of participants in each trial varied between 14 and 129 with a total of 512 participants included in the review. All the included trials were for a duration of four weeks. The included trials had mostly an unclear risk of bias from the randomisation process as the details of this were not given; they also mostly had a high risk of attrition bias and reporting bias.We could not combine data from all the trials as they compared different formulations. Findings from individual studies provided insufficient evidence to determine the size and precision of the effects of different formulations. Ten studies reported information on the review's primary outcome (nutritional status); however, we were only able to combine data from two small cross-over studies (n = 41). The estimated gain in body weight was imprecise, 0.32 kg (95% confidence interval -0.03 to 0.67; P = 0.07). Combined data from the same studies gave statistically significant results favouring enteric-coated microspheres over enteric-coated tablets for our secondary outcomes stool frequency, mean difference -0.58 (95% confidence interval -0.85 to -0.30; P < 0.0001); proportion of days with abdominal pain, mean difference -7.96% (95% confidence interval -12.97 to -2.94; P = 0.002); and fecal fat excretion, mean difference -11.79 g (95% confidence interval -17.42 to -6.15; P < 0.0001). Data from another single small cross-over study also favoured enteric-coated microspheres over non-enteric-coated tablets with adjuvant cimetidine in terms of stool frequency, mean difference -0.70 (95% confidence interval -0.90 to -0.50; P < 0.00001). There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over studies is likely to underestimate the level of inconsistency between the results of the studies due to over-inflation of confidence intervals from the individual studies.There is no evidence on the long-term effectiveness and risks associated with pancreatic enzyme replacement therapy. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed study that can answer these questions.

Avoidance of bottles during the establishment of breast feeds in preterm infants.

Preterm infants start milk feeds by gavage tube. As they mature, sucking feeds are gradually introduced. Women who choose to breast feed their preterm infant are not always able to be in hospital with their baby and need an alternative approach to feeding. Most commonly, milk (expressed breast milk or formula) is given by bottle. Whether using bottles during establishment of breast feeds is detrimental to breast feeding success is a topic of ongoing debate. To identify the effects of avoidance of bottle feeds during establishment of breast feeding on the likelihood of successful breast feeding, and to assess the safety of alternatives to bottle feeds. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE via PubMed (1966 to July 2016), Embase (1980 to July 2016) and CINAHL (1982 to July 2016). We also searched databases of clinical trials and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised and quasi-randomised controlled trials comparing avoidance of bottles with use of bottles in women who have chosen to breast feed their preterm infant. Two review authors independently assessed trial quality and extracted data. When appropriate, we contacted study authors for additional information. Review authors used standard methods of The Cochrane Collaboration and the Cochrane Neonatal Review Group. We included seven trials with 1152 preterm infants. Five studies used a cup feeding strategy, one used a tube feeding strategy and one used a novel teat when supplements to breast feeds were needed. We included the novel teat study in this review, as the teat was designed to more closely mimic the sucking action of breast feeding. The trials were of small to moderate size, and two had high risk of attrition bias. Adherence with cup feeding was poor in one of the studies, indicating dissatisfaction with this method by staff and/or parents; the remaining four cup feeding studies provided no such reports of dissatisfaction or low adherence. Meta-analyses provided evidence of low to moderate quality indicating that avoiding bottles increases the extent of breast feeding on discharge home (full breast feeding typical risk ratio (RR) 1.47, 95% confidence interval (CI) 1.19 to 1.80; any breast feeding RR 1.11, 95% CI 1.06 to 1.16). Limited available evidence for three months and six months post discharge shows that avoiding bottles increases the occurrence of full breast feeding and any breast feeding at discharge and at six months post discharge, and of full (but not any) breast feeding at three months post discharge. This effect was evident at all time points for the tube alone strategy and for all except any breast feeding at three months post discharge for cup feeding. Investigators reported no clear benefit when the novel teat was used. No other benefits or harms were evident, including, in contrast to the previous (2008) review, length of hospital stay. Evidence of low to moderate quality suggests that supplementing breast feeds by cup increases the extent and duration of breast feeding. Current insufficient evidence provides no basis for recommendations for a tube alone approach to supplementing breast feeds.

Household interventions for preventing domestic lead exposure in children.

Household interventions for preventing domestic lead exposure in children.

Short-term and long-term effects of tibolone in postmenopausal women.

Short-term and long-term effects of tibolone in postmenopausal women.

Avoidance of bottles during the establishment of breast feeds in preterm infants.

Preterm infants start milk feeds by gavage tube. As they mature, sucking feeds are gradually introduced. Women who choose to breast feed their preterm infant are not always able to be in hospital with their baby and need an alternative approach to feeding. Most commonly, milk (expressed breast milk or formula) is given by bottle. Whether using bottles during establishment of breast feeds is detrimental to breast feeding success is a topic of ongoing debate. To identify the effects of avoidance of bottle feeds during establishment of breast feeding on the likelihood of successful breast feeding, and to assess the safety of alternatives to bottle feeds. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE via PubMed (1966 to July 2016), Embase (1980 to July 2016) and CINAHL (1982 to July 2016). We also searched databases of clinical trials and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised and quasi-randomised controlled trials comparing avoidance of bottles with use of bottles in women who have chosen to breast feed their preterm infant. Two review authors independently assessed trial quality and extracted data. When appropriate, we contacted study authors for additional information. Review authors used standard methods of The Cochrane Collaboration and the Cochrane Neonatal Review Group. We included seven trials with 1152 preterm infants. Five studies used a cup feeding strategy, one used a tube feeding strategy and one used a novel teat when supplements to breast feeds were needed. We included the novel teat study in this review, as the teat was designed to more closely mimic the sucking action of breast feeding. The trials were of small to moderate size, and two had high risk of attrition bias. Adherence with cup feeding was poor in one of the studies, indicating dissatisfaction with this method by staff and/or parents; the remaining four cup feeding studies provided no such reports of dissatisfaction or low adherence. Meta-analyses provided evidence of low to moderate quality indicating that avoiding bottles increases the extent of breast feeding on discharge home (full breast feeding typical risk ratio (RR) 1.47, 95% confidence interval (CI) 1.19 to 1.80; any breast feeding RR 1.11, 95% CI 1.06 to 1.16). Limited available evidence for three months and six months post discharge shows that avoiding bottles increases the occurrence of full breast feeding and any breast feeding at discharge and at six months post discharge, and of full (but not any) breast feeding at three months post discharge. This effect was evident at all time points for the tube alone strategy and for all except any breast feeding at three months post discharge for cup feeding. Investigators reported no clear benefit when the novel teat was used. No other benefits or harms were evident, including, in contrast to the previous (2008) review, length of hospital stay. Evidence of low to moderate quality suggests that supplementing breast feeds by cup increases the extent and duration of breast feeding. Current insufficient evidence provides no basis for recommendations for a tube alone approach to supplementing breast feeds.

Iron supplementation to treat anaemia in adult critical care patients: a systematic review and meta-analysis.

BackgroundAnaemia affects 60–80 % of patients admitted to intensive care units (ICUs). Allogeneic red blood cell (RBC) transfusions remain the mainstay of treatment for anaemia but are associated with risks and are costly. Our objective was to assess the efficacy and safety of iron supplementation by any route, in anaemic patients in adult ICUs.MethodsElectronic databases (CENTRAL, MEDLINE, EMBASE) were searched through March 2016 for randomized controlled trials (RCT)s comparing iron by any route with placebo/no iron. Primary outcomes were red blood cell transfusions and mean haemoglobin concentration. Secondary outcomes included mortality, infection, ICU and hospital length of stay, mean difference (MD) in iron biomarkers, health-related quality of life and adverse events.ResultsFive RCTs recruiting 665 patients met the inclusion criteria; intravenous iron was tested in four of the RCTs. There was no difference in allogeneic RBC transfusion requirements (relative risk 0.87, 95 % confidence interval (CI) 0.70 to 1.07, p = 0.18, five trials) or mean number of RBC units transfused (MD -0.45, 95 % CI -1.34 to 0.43, p = 0.32, two trials) in patients receiving or not receiving iron. Similarly, there was no difference between groups in haemoglobin at short-term (up to 10 days) (MD -0.25, 95 % CI -0.79 to 0.28, p = 0.35, three trials) or mid-term follow up (last measured time point in hospital or end of trial) (MD 0.21, 95 % CI -0.13 to 0.55, p = 0.23, three trials). There was no difference in secondary outcomes of mortality, in-hospital infection, or length of stay. Risk of bias was generally low although three trials had high risk of attrition bias; only one trial had low risk of bias across all domains.ConclusionIron supplementation does not reduce RBC transfusion requirements in critically ill adults, but there is considerable heterogeneity between trials in study design, nature of interventions, and outcomes. Well-designed trials are needed to investigate the optimal iron dosing regimens and strategies to identify which patients are most likely to benefit from iron, together with patient-focused outcomes.Trial registrationPROSPERO International prospective register of systematic reviews CRD42015016627. Registered 2 March 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1486-z) contains supplementary material, which is available to authorized users.

Endothelin receptor antagonists for persistent pulmonary hypertension in term and late preterm infants.

Endothelin, a powerful vasoconstrictor, is one of the mediators in the causation of persistent pulmonary hypertension of the newborn (PPHN). Theoretically, endothelin receptor antagonists (ETRA) have the potential to improve the outcomes of infants with PPHN. To assess the efficacy and safety of ETRA in the treatment of PPHN in full-term, post-term and late preterm infants.To assess the efficacy and safety of selective ETRAs (which block only the ETA receptors) and non-selective ETRAs (which block both ETA and ETB receptors) separately. CENTRAL (Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE and CINAHL databases were searched until December 2015. Randomised, cluster-randomised or quasi-randomised controlled trials were eligible. Two review authors independently searched the literature, selected the studies, assessed the risk of bias and extracted the data. A fixed-effect model was used for meta-analysis. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. Two randomised controlled trials of ETRA met the inclusion criteria. Both studies utilized oral Bosentan. The first study was done in a setting where inhaled nitric oxide (iNO) therapy was not available. Forty-seven infants (≥ 34 weeks' gestation) were randomised to receive either Bosentan or placebo. The second study was a multicentre study where iNO therapy was the standard of care for PPHN. Twenty-one infants were randomised to receive either 'iNO plus Bosentan' or 'iNO plus placebo'.In the first study, there was no significant difference in the incidence of death before hospital discharge between the Bosentan and placebo groups (1/23 vs 3/14; RR 0.20, 95% CI 0.02 to 1.77; RD -0.17, 95% CI -0.40 to 0.06). A higher proportion of infants in the Bosentan group showed improvement in oxygenation index (OI) at the end of therapy (21/24 vs 3/15; RR 4.38, 95% CI 1.57 to 12.17; RD 0.68, 95% CI 0.43 to 0.92; number needed to treat for a beneficial outcome (NNTB) 1.5). The duration of mechanical ventilation was lower in the Bosentan group (4.3 ± 0.9 vs 11.5 ± 0.6 days; MD -7.20, 95% CI -7.64 to -6.76). There was no significant difference in adverse neurological outcomes at six months (0/23 vs 4/14; RR 0.07, 95% CI 0.00 to 1.20; RD -0.29, 95% CI -0.52 to -0.05). The study suffered from a high risk of attrition bias since 8/23 infants in the placebo group were excluded from various analyses. Since the protocol for the study could not be accessed, the study suffered from unclear risk of reporting bias.In the second study, there was no significant difference in the incidence of treatment failure needing extracorporeal membrane oxygenation (ECMO) between the 'iNO plus Bosentan' vs 'iNO plus placebo' groups (1/13 vs 0/8; RR 1.93, 95% CI 0.09 to 42.35; RD 0.08, 95% CI -0.14 to 0.30). There was no significant difference in the median time to wean from iNO ('iNO plus Bosentan': 3.7 days (95% CI 1.17 to 6.95); 'iNO plus placebo': 2.9 days (95% CI 1.26 to 4.23); P = 0.34). There were no significant differences in the OI 0, 3, 5, 12, 24, 48 and 72 hours of treatment between the groups. There were no significant differences in the time to complete weaning from mechanical ventilation (median 10.8 days (CI 3.21 to 12.21) versus 8.6 days (CI 3.71 to 9.66); P = 0.24). The study had unequal distribution to the Bosentan group (N = 13) and the placebo group (N = 8). The methods used for generating random sequence numbers and allocation concealment were unclear, resulting in unclear risk of selection bias.Both studies reported that Bosentan was well tolerated and no major adverse effects were noted. Data from the two studies was not pooled given the heterogenous nature of the clinical settings and the modalities used for the treatment of PPHN.Overall, the quality of evidence was considered low, given the small sample size of the included studies, the numerical imbalance between the groups due to randomisation and attrition, and unclear risk of bias on some of the important domains. There is inadequate evidence to support the use of ETRAs either as stand-alone therapy or as adjuvant to inhaled nitric oxide in PPHN. Adequately powered RCTs are needed.

Safety and Efficacy of Incretin-Based Therapies in Patients With Type 2 Diabetes Mellitus and CKD: A Systematic Review and Meta-analysis

The pharmacokinetics and pharmacodynamics of antidiabetic therapies for patients with type2 diabetes are often altered in the context of chronic kidney disease (CKD). Systematic review and meta-analysis. Patients with type 2 diabetes and CKD. 2 reviewers independently screened studies identified through bibliographic databases (Cochrane Library, PubMed, Embase, International Pharmaceutical Abstracts), clinical trial registries, and references from pertinent articles and clinical practice guidelines. Eligible studies included randomized controlled trials evaluating incretin-based therapy in adults with type 2 diabetes and estimated glomerular filtration rates< 60mL/min/1.73m2. Incretin-based therapies (dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists) compared to placebo or active antidiabetic therapies. Changes in glycated hemoglobin (HbA1c), hypoglycemia, mortality, change in fasting plasma glucose, cardiovascular events, and end-stage renal disease. Of 1,619 nonduplicate records screened, 13 studies were included. Compared to placebo, incretin-based therapies significantly reduced HbA1c levels (n= 9; weighted mean difference,-0.64; 95% CI,-0.79 to-0.48; I2= 43%); however, compared with active comparators, they did not (n= 4; weighted mean difference,-0.07; 95% CI,-0.25 to 0.12; I2= 38%). Incretin-based therapies significantly increased the risk for hypoglycemia compared to placebo (n= 7; relative risk [RR], 1.38; 95% CI, 1.01-1.89; I2= 0%) but no effect was observed versus active comparators (n= 4; RR, 0.24; 95% CI, 0.03-1.94; I2= 52%). Limited evidence exists for all-cause mortality (placebo: n= 7 [RR, 1.21; 95% CI, 0.64-2.29; I2= 0%]; active comparators: n= 3 [RR, 0.70; 95% CI, 0.32-1.54; I2= 0%]). Variation among interventions, small number of studies, heterogeneity between studies, and high risk for attrition bias in 7 of the selected studies. In patients with moderate or severe CKD, incretin-based therapies are effective in reducing HbA1c levels. Hypoglycemic events are rare, and wide CIs for the association preclude any definitive conclusions. Likewise, wide CIs were observed for mortality, cardiovascular events, and end-stage renal disease.

Bioabsorbable versus metallic interference screws for graft fixation in anterior cruciate ligament reconstruction.

Bioabsorbable versus metallic interference screws for graft fixation in anterior cruciate ligament reconstruction.

Different types of implants for reconstructive breast surgery.

Different types of implants for reconstructive breast surgery.

Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis.

Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis.

Teriflunomide for multiple sclerosis.

Teriflunomide for multiple sclerosis.

Corticosteroids for septic arthritis in children

Background: Septic arthritis is an acute infection of the joints characterised by erosive disruption of the articular space. It is the most common non-degenerative articular disease in developing countries. The most vulnerable population for septic arthritis includes infants and preschoolers, especially boys. Septic arthritis disproportionately affects populations of low socioeconomic status. Systemic corticosteroids and antibiotic therapy may be beneficial for treatment of septic arthritis. Even if the joint infection is eradicated by antibiotic treatment, the inflammatory process may produce residual joint damage and sequelae. Objectives: To determine the benefits and harms of corticosteroids as adjunctive therapy in children with a diagnosis of septic arthritis. Search methods: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, Latin American Caribbean Health Sciences Literature (LILACS), the World Health Organization (WHO) trials portal (www.who.int/ictrp/en/), ClinicalTrials.gov (www.ClinicalTrials.gov), and Google Scholar. We searched all databases from their inception to 17 April 2018, with no restrictions on language of publication. Selection criteria: We included randomised controlled trials (RCTs) with patients from two months to 18 years of age with a diagnosis of septic arthritis who were receiving corticosteroids in addition to antibiotic therapy or as an adjuvant to other therapies such as surgical drainage, intra-articular puncture, arthroscopic irrigation, or debridement. Data collection and analysis: Two review authors independently assessed eligibility, data extraction, and evaluation of risk of bias. We considered as major outcomes the presence of pain, activities of daily living, normal physical joint function, days of antibiotic treatment, length of hospital stay, and numbers of total and serious adverse events. We used standard methodological procedures expected by Cochrane. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table. Main results: We included two RCTs involving a total of 149 children between three months and 18 years of age who were receiving antibiotics for septic arthritis. The most commonly affected joints were hips and knees. These studies were performed in Costa Rica and Israel. In both studies, dexamethasone administered intravenously (ranging from 0.15 to 0.2 mg/kg/dose every six to eight hours) during four days was the corticosteroid, and the comparator was placebo. Trials excluded patients with any degree of immunodeficiency or immunosuppression. The longest follow-up was one year. Trials did not report activities of daily living nor length of hospital stay. Both studies used adequate processes for randomisation, allocation concealment, and blinding, and review authors judged them to have low risk of selection and performance bias. Losses to follow-up were substantive in both studies, and we judged them to have high risk of attrition bias and of selective outcome reporting. We graded all outcomes as low quality due to concerns about study limitations and imprecision. The risk ratio (RR) for absence of pain at 12 months of follow-up was 1.33, favouring corticosteroids (95% confidence interval (CI) 1.03 to 1.72; P = 0.03; number needed to treat for an additional beneficial outcome (NNTB) = 13, 95% CI 6 to 139; absolute risk difference 24%, 95% CI 5% to 43%). The RR for normal function of the affected joint at 12 months of follow-up was 1.32, favouring corticosteroids (95% CI 1.12 to 1.57; P = 0.001; NNTB = 13, 95% CI 7 to 33; absolute risk difference 24%, 95% CI 11% to 37%). We found a reduction in the number of days of intravenous antibiotic treatment favouring corticosteroids (mean difference (MD) -2.77, 95% CI -4.16 to -1.39) based on two trials with 149 participants. Researchers did not report length of hospital stay. One trial (49 participants) reported that treatment with dexamethasone was associated with a shorter duration of IV antibiotic treatment, leading to a shorter hospital stay, and although duration of hospitalisation was a primary outcome of the study, study authors did not provide data on the duration of hospitalisation. We downgraded the quality by one level for concerns about study limitations (high risk of attrition bias and selective reporting), and by another level for imprecision. In one trial of 49 participants, researchers followed 29 children for 12 months, and parents reported that no children demonstrated adverse effects of the intervention. Authors' conclusions: Evidence for corticosteroids as adjunctive therapy in children with a diagnosis of septic arthritis is of low quality and is derived from the findings of two trials (N = 149). Corticosteroids may increase the proportion of patients without pain and the proportion of patients with normal function of the affected joint at 12 months, and may also reduce the number of days of antibiotic treatment. However, we cannot draw strong conclusions based upon these trial results. Additional randomised clinical trials in children with relevant outcomes are needed.

Meditation for adults with haematological malignancies.

Malignant neoplasms of the lymphoid or myeloid cell lines including lymphoma, leukaemia and myeloma are referred to as haematological malignancies. Complementary and alternative treatment options such as meditation practice or yoga are becoming popular by treating all aspects of the disease including physical and psychological symptoms. However, there is still unclear evidence about meditation's effectiveness, and how its practice affects the lives of haematologically-diseased patients. This review aims to assess the benefits and harms of meditation practice as an additional treatment to standard care for adults with haematological malignancies. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 8, 2015), MEDLINE (1950 to August 2015), databases of ongoing trials, the metaRegister of Controlled Trials (mRCT) (http://www.controlled-trials.com/mrct/), conference proceedings of annual meetings of: the American Society of Hematology; American Society of Clinical Oncology; European Hematology Association; European Congress for Integrative Medicine; and Global Advances in Health and Medicine (2010 to 2015). We included randomised controlled trials (RCTs) using meditation practice for adult patients with haematological malignancies. Two review authors independently extracted data from eligible studies and assessed the risk of bias according to predefined criteria. We evaluated quality of life and depression. The other outcomes of overall survival, anxiety, fatigue, quality of sleep and adverse events could not be evaluated, because they were not assessed in the included trial. We included only one small trial published as an abstract article. The included study investigated the effects of meditation practice on patients newly hospitalised with acute leukaemia. Ninety-one participants enrolled in the study, but only 42 participants remained in the trial throughout the six-month follow-up period and were eligible for analysis. There was no information provided about the average age and sex of the study population. We found a high risk for attrition bias and unclear risk for reporting bias, performance and detection bias because of missing data due to abstract publication only, thus we judged the overall risk of bias as high. According to the GRADE criteria, we judged the overall quality of the body of evidence for all predefined outcomes as 'very low', due to the extent of missing data on the study population, and the small sample size.As the abstract publication did not provide numbers and results except P values, we are not able to give more details.Meditation practice might be beneficial for the quality of life of haematologically-diseased patients, with higher scores for participants in the mediation arms compared to the participants in the usual care control group (low quality of evidence). Levels of depression decreased for those practising meditation in both the spiritually-framed meditation group and the secularly-focused meditation group in comparison to the usual care control group, whose levels of depression remained constant (low quality of evidence). The influence of meditation practice on overall survival, fatigue, anxiety, quality of sleep and adverse events remained unclear, as these outcomes were not evaluated in the included trial. To estimate the effects of meditation practice for patients suffering from haematological malignancies, more high quality randomised controlled trials are needed. At present there is not enough information available on the effects of meditation in haematologically-diseased patients to draw any conclusion.

Anion gap as a prognostic tool for risk stratification in critically ill patients - a systematic review and meta-analysis.

BackgroundLactate concentration is a robust predictor of mortality but in many low resource settings facilities for its analysis are not available. Anion gap (AG), calculated from clinical chemistry results, is a marker of metabolic acidosis and may be more easily obtained in such settings. In this systematic review and meta-analysis we investigated whether the AG predicts mortality in adult patients admitted to critical care settings.MethodsWe searched Medline, Embase, Web of Science, Scopus, The Cochrane Library and regional electronic databases from inception until May 2016. Studies conducted in any clinical setting that related AG to in-hospital mortality, in-intensive care unit mortality, 31-day mortality or comparable outcome measures were eligible for inclusion. Methodological quality of included studies was assessed using the Quality in Prognostic Studies tool. Descriptive meta-analysis was performed and the I2 test was used to quantify heterogeneity. Subgroup analysis was undertaken to identify potential sources of heterogeneity between studies.ResultsNineteen studies reporting findings in 12,497 patients were included. Overall, quality of studies was poor and most studies were rated as being at moderate or high risk of attrition bias and confounding. There was substantial diversity between studies with regards to clinical setting, age and mortality rates of patient cohorts. High statistical heterogeneity was found in the meta-analyses of area under the ROC curve (I2 = 99 %) and mean difference (I2 = 97 %) for the observed AG. Three studies reported good discriminatory power of the AG to predict mortality and were responsible for a large proportion of statistical heterogeneity. The remaining 16 studies reported poor to moderate ability of the AG to predict mortality. Subgroup analysis suggested that intravenous fluids affect the ability of the AG to predict mortality.ConclusionBased on the limited quality of available evidence, a single AG measurement cannot be recommended for risk stratification in critically ill patients. The probable influence of intravenous fluids on AG levels renders the AG an impractical tool in clinical practice. Future research should focus on increasing the availability of lactate monitoring in low resource settings.PROSPERO registration number CRD42015015249. Registered on 4th February 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s12871-016-0241-y) contains supplementary material, which is available to authorized users.