Risk Of Bias In Studies Research Articles

RoB-SPEO: A tool for assessing risk of bias in studies estimating the prevalence of exposure to occupational risk factors from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury

BackgroundThe World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates). For this, systematic reviews of studies estimating the prevalence of exposure to selected occupational risk factors will be conducted to provide input data for estimations of the number of exposed workers. A critical part of systematic review methods is to assess risk of bias (RoB) of individual studies. In this article, we present and describe the development of such a tool, called the Risk of Bias in Studies estimating Prevalence of Exposure to Occupational risk factors (RoB-SPEO) tool; report results from RoB-SPEO's pilot testing; note RoB-SPEO's limitations; and suggest how the tool might be tested and developed further. MethodsSelected existing RoB tools used in environmental and occupational health systematic reviews were reviewed and analysed. From existing tools, we identified domains for the new tool and, if necessary, added new domains. For each domain, we then identified and integrated components from the existing tools (i.e. instructions, domains, guiding questions, considerations, ratings and rating criteria), and, if necessary, we developed new components. Finally, we elicited feedback from other systematic review methodologists and exposure scientists and agreed upon RoB-SPEO. Nine experts pilot tested RoB-SPEO, and we calculated a raw measure of inter-rater agreement (Pi) for each of its domain, rating Pi < 0.4 as poor, 0.4 ≤ Pi ≥ 0.8 as substantial and Pi > 0.80 as almost perfect agreement. ResultsOur review found no standard tool for assessing RoB in prevalence studies of exposure to occupational risk factors. We identified six existing tools for environmental and occupational health systematic reviews and found that their components for assessing RoB differ considerably. With the new RoB-SPEO tool, assessors judge RoB for each of eight domains: (1) bias in selection of participants into the study; (2) bias due to a lack of blinding of study personnel; (3) bias due to exposure misclassification; (4) bias due to incomplete exposure data; (5) bias due to conflict of interest; (6) bias due to selective reporting of exposures; (7) bias due to difference in numerator and denominator; and (8) other bias. The RoB-SPEO's ratings are low, probably low, probably high, high or no information. Pilot testing of the RoB-SPEO tool found substantial inter-rater agreement for six domains (range of Pi for these domains: 0.51–0.80), but poor agreement for two domains (i.e. Pi of 0.31 and 0.33 for biases due to incomplete exposure data and in selection of participants into the study, respectively). Limitations of RoB-SPEO include that it has not yet been fully performance-tested. ConclusionsWe developed the RoB-SPEO tool for assessing RoB in prevalence studies of exposure to occupational risk factors. The tool will be applied and its performance tested in the ongoing systematic reviews for the WHO/ILO Joint Estimates.

Methods and Risks of Bias in Natural Experiments in Obesity: Opportunities for the Future Informed by a Systematic Review.

This paper promotes rigorous methods and designs currently underutilized in obesity research, informed by a recent systematic review of the methods and risks of bias in studies of policies, programs, and built environment changes for obesity prevention and control. To determine the current state of the field, relevant databases from 2000 to 2017 were searched to identify studies that fit the inclusion criteria. Study design, analytic approach, and other details of study methods were abstracted. These findings inform recommendations for obesity researchers and the field as a whole. Previously identified were 156 natural experiment studies. Most were cross-sectional (35%), pre-post single group comparison (31%), or difference-in-differences designs (29%). Few used rigorous causal designs such as interrupted time series with more than two time points, propensity score methods, or instrumental variables. The potential relevance for obesity research is discussed, and recommendations for obesity researchers are provided. To strengthen natural experiment study designs and enhance the validity of results, researchers should carefully consider and control for confounding and selection of comparison groups and consider study designs that address these biases.

Early Mortality Rates After Commencement of Maintenance Hemodialysis: A Systematic Review and Meta-Analysis.

Mortality rates are reported to be high soon after the commencement of maintenance HD for ESRD. Our aim was to estimate early mortality rates (deaths within 180 days of starting therapy), through a systematic review of literature, in this patient population. Medline and EMBASE were searched for publications between 1 January 1985 and 31 December 2017. Observational studies reporting deaths involving adults commencing HD were included. The Quality in Prognosis Studies tool was used to assess risk of bias in studies. Crude mortality rates (expressed in 100 person-years) and age-standardized mortality ratios (SMR) were calculated. Meta-analyses of these rates were conducted for studies with lowest risk of bias (i.e. highest quality). In total, 32 studies were included (combined population: 1 083 264) representing 283 277 person-years of observation; median follow-up: 90 days. Mortality rates ranged between 12.8 and 55.6 per 100 person-years. Cardiovascular causes accounted for the majority of early deaths. Meta-analysis of high-quality studies showed an overall crude mortality rate of 32.6 per 100 person-years (95% CI 32.4-32.8). This equates to 16.3% mortality in first 180 days of starting HD. Six high-quality studies contained sufficient data for calculation of SMR. Meta-analysis of SMRs showed that patients starting HD therapy sustain 8.8 times higher mortality rates compared to the general population. We have combined the results of high-quality studies to produce new estimates of early mortality rates after commencement of HD therapy. This information can help relay more reliable prognostic information to this patient population.

Antiepileptic drugs for seizure control in people with neurocysticercosis.

Neurocysticercosis is the most common parasitic infection of the brain. Epilepsy is the most common clinical presentation, though it may also present with headache, symptoms of raised intracranial pressure, hydrocephalus and ocular symptoms depending upon the localisation of the parasitic cysts. Anthelmintic drugs, anti-oedema drugs, such as steroids, and antiepileptic drugs (AEDs) form the mainstay of treatment.This is an updated version of the original Cochrane Review published in 2015, Issue 10. To assess the effects (benefits and harms) of AEDs for the primary and secondary prevention of seizures in people with neurocysticercosis.For the question of primary prevention, we examined whether AEDs reduce the likelihood of seizures in patients who have neurocysticercosis but have not had a seizure.For the question of secondary prevention, we examined whether AEDs reduce the likelihood of further seizures in patients who have had at least one seizure due to neurocysticercosis.As part of primary prevention studies, we also aimed to examine which AED has been found to be beneficial in people with neurocysticercosis in terms of duration, dose and side-effect profile. For the latest update of this review, we searched the following databases on 8 July 2019: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to July 05, 2019) and LILACS (1982- ). CRS Web includes the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised or quasi-randomised, controlled trials from Embase, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP). We also checked the references lists of identified studies, and contacted experts in the field and colleagues to search for additional studies and for information about ongoing studies. Randomised and quasi-randomised controlled trials.Single-blind, double-blind or unblinded studies were eligible for inclusion. Two review authors screened all citations for eligibility (MS screened the initially identified 180 citations, MF and BDM screened the 48 citations identified for the purpose of this update).Two review authors independently extracted data and evaluated each study for risk of bias. We did not find any trials that investigated the role of AEDs in preventing seizures among people with neurocysticercosis, presenting with symptoms other than seizures.We did not find any trials that evaluated evaluating individual AEDs in people with neurocysticercosis.We found one trial, comparing two AEDs in people with solitary neurocysticercosis with seizures. However, we excluded this study from the review as it was of poor quality.We found four trials that compared the efficacy of short term versus longer term AED treatment for people with solitary neurocysticercosis (identified on computed tomography (CT) scan) presenting with seizures. In total, 466 people were enrolled. These studies compared various AED treatment durations, six, 12 and 24 months. The risk of seizure recurrence with six months treatment compared with 12 to 24 months treatment was not statistically significant (odds ratio (OR) 1.34 (95% confidence interval (CI) 0.73 to 2.47; three studies, 360 participants; low-certainty evidence)). The risk of seizure recurrence with six to 12 months compared with 24 months treatment was not statistically significant (OR 1.36 (95% CI 0.72 to 2.57; three studies, 385 participants; low-certainty evidence)).Two studies co-related seizure recurrence with CT findings and suggested that persistent and calcified lesions had a higher recurrence risk and suggest longer duration of treatment with AEDs. One study reported no side effects, while the rest did not comment on side effects of drugs. None of the studies addressed the quality of life of the participants.These studies had certain methodological deficiencies such as a small sample size and a possibility of bias due to lack of blinding, which affect the results of this review. Despite neurocysticercosis being the most common cause of epilepsy worldwide, there is currently no evidence available regarding the use of AEDs as seizure prophylaxis among people presenting with symptoms other than seizures. For those presenting with seizures, there is no reliable evidence regarding the duration of treatment required. There is therefore a need for large scale randomised controlled trials to address these questions.

The role of vitamin D in increasing circulating T regulatory cell numbers and modulating T regulatory cell phenotypes in patients with inflammatory disease or in healthy volunteers: A systematic review.

BackgroundThe evidence for vitamin D and other agents that experimentally modulate T regulatory cells (Tregs) for the treatment of patients with autoimmune or allergic diseases has not been established.ObjectiveWe have undertaken a systematic review of randomised controlled trials to assess the efficacy of vitamin D, vitamin A, niacin and short-chain fatty acids in enhancing absolute Treg numbers and phenotypes in patients with inflammatory or autoimmune disease.MethodsThis systematic review was conducted using a predefined protocol (PROSPERO International prospective register of systematic reviews, ID = CRD42016048648/ CRD42016048646). Randomised controlled trials of patients with inflammatory or autoimmune disease or healthy participants which compared either oral vitamin D or vitamin A or short-chain fatty acids with control or placebo and measured the absolute concentration of proportion of Tregs were eligible for inclusion. Searches of electronic databases (CENTRAL, MEDLINE, EMBASE, CINAHL, PUBMED and Web of Science) identified eight eligible independent trials (seven autoimmune disease trials, one trial of healthy subjects). Data were extracted by two reviewers and the risk of study bias was assessed using Cochrane Collaboration methodology.ResultsPlanned meta-analysis was not possible due to the heterogeneous nature of the studies. Nevertheless, in five trials of autoimmune disorders which measured the proportion of Tregs, a higher proportion was observed in the vitamin D group compared to controls at 12 months in all but one trial. In the trial of healthy subjects, a significant difference was reported, with a higher percentage of Tregs observed in the vitamin D group (at 12 weeks, mean 6.4% (SD 0.8%) (vitamin D) vs 5.5% (1.0%) (placebo). There were no trials to assess the efficacy of vitamin A, niacin and short-chain fatty acids in enhancing absolute Treg numbers.ConclusionsVitamin D supplementation may increase Treg/CD3 ratios in both healthy individuals and patients with autoimmune disorders and may increase Treg function. There remains a need for further suitably powered clinical studies aimed at enhancing Treg numbers and/or function.

Rectovaginal group B streptococcus colonization among pregnant women in Nicaragua: a systematic review and meta-analysis

Background Maternal colonization with group B Streptococcus (GBS) is a predictor of neonatal sepsis. In Nicaragua, neonatal sepsis is a major cause of hospitalization, but it can be prevented with intrapartum antibiotic prophylaxis. We undertook this study to estimate the pooled prevalence of rectovaginal GBS colonization among pregnant women 35–40-week gestation in Nicaragua, and sensitivity of GBS isolates to various antibiotics. Methods We systematically searched electronic databases of peer-reviewed and unpublished literature using prespecified search terms. We included English- and Spanish-language studies of rectovaginal GBS colonization and/or antibiotic sensitivity of GBS isolates that followed internationally-recognized diagnostic standards, from various sites and years. Two reviewers independently abstracted data and assessed risk of study bias. We then meta-analyzed the pooled prevalence of rectovaginal GBS colonization and antibiotic sensitivity of GBS isolates. We performed subgroup analyses by geographic location, urbanicity, and study risk of bias. Main results Prevalence of rectovaginal GBS colonization from 13 samples in 11 studies was 0.14 (95% CI: 0.09, 0.21). Effect size heterogeneity was identified between coastal (0.12 [95% CI: 0.07, 0.19]) and central study sites (0.23 [95% CI: 0.18, 0.28]), and between predominantly rural (0.06 [95% CI: 0.02, 0.10]) and urban (0.28 [95% CI: 0.19, 0.37]) samples of pregnant women. GBS sensitivity to penicillin, the first-line antibiotic for intrapartum prophylaxis, was 0.89 (95% CI: 0.71, 1.00) based on seven studies. Conclusions Maternal GBS colonization was substantial in some study sites. Most GBS isolates are sensitive to recommended antibiotics, and intrapartum antibiotic prophylaxis may effectively prevent neonatal sepsis in Nicaragua.

Exercise for dysmenorrhoea.

Exercise has a number of health benefits and has been recommended as a treatment for primary dysmenorrhoea (period pain), but the evidence for its effectiveness on primary dysmenorrhoea is unclear. This review examined the available evidence supporting the use of exercise to treat primary dysmenorrhoea. To evaluate the effectiveness and safety of exercise for women with primary dysmenorrhoea. We searched the Cochrane Gynaecology and Fertility specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, AMED and CINAHL (from inception to July 2019). We searched two clinical trial databases (inception to March 2019) and handsearched reference lists and previous systematic reviews. We included studies if they randomised women with moderate-to-severe primary dysmenorrhoea to receive exercise versus no treatment, attention control, non-steroidal anti-inflammatory drugs (NSAIDs) or the oral contraceptive pill. Cross-over studies and cluster-randomised trials were not eligible for inclusion. Two review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data from each study. We contacted study authors for missing information. We assessed the quality of the evidence using GRADE. Our primary outcomes were menstrual pain intensity and adverse events. Secondary outcomes included overall menstrual symptoms, usage of rescue analgesic medication, restriction of daily life activities, absence from work or school and quality of life. We included a total of 12 trials with 854 women in the review, with 10 trials and 754 women in the meta-analysis. Nine of the 10 studies compared exercise with no treatment, and one study compared exercise with NSAIDs. No studies compared exercise with attention control or with the oral contraceptive pill. Studies used low-intensity exercise (stretching, core strengthening or yoga) or high-intensity exercise (Zumba or aerobic training); none of the included studies used resistance training.Exercise versus no treatmentExercise may have a large effect on reducing menstrual pain intensity compared to no exercise (standard mean difference (SMD) -1.86, 95% confidence interval (CI) -2.06 to -1.66; 9 randomised controlled trials (RCTs), n = 632; I2= 91%; low-quality evidence). This SMD corresponds to a 25 mm reduction on a 100 mm visual analogue scale (VAS) and is likely to be clinically significant. We are uncertain if there is any difference in adverse event rates between exercise and no treatment.We are uncertain if exercise reduces overall menstrual symptoms (as measured by the Moos Menstrual Distress Questionnaire (MMDQ)), such as back pain or fatigue compared to no treatment (mean difference (MD) -33.16, 95% CI -40.45 to -25.87; 1 RCT, n = 120; very low-quality evidence), or improves mental quality of life (MD 4.40, 95% CI 1.59 to 7.21; 1 RCT, n = 55; very low-quality evidence) or physical quality of life (as measured by the 12-Item Short Form Health Survey (SF-12)) compared to no exercise (MD 3.40, 95% CI -1.68 to 8.48; 1 RCT, n = 55; very low-quality evidence) when compared to no treatment. No studies reported on any changes in restriction of daily life activities or on absence from work or school.Exercise versus NSAIDsWe are uncertain if exercise, when compared with mefenamic acid, reduced menstrual pain intensity (MD -7.40, 95% CI -8.36 to -6.44; 1 RCT, n = 122; very low-quality evidence), use of rescue analgesic medication (risk ratio (RR) 1.77, 95% CI 1.21 to 2.60; 1 RCT, n = 122; very low-quality evidence) or absence from work or school (RR 1.00, 95% CI 0.49 to 2.03; 1 RCT, n = 122; very low-quality evidence). None of the included studies reported on adverse events, overall menstrual symptoms, restriction of daily life activities or quality of life. The current low-quality evidence suggests that exercise, performed for about 45 to 60 minutes each time, three times per week or more, regardless of intensity, may provide a clinically significant reduction in menstrual pain intensity of around 25 mm on a 100 mm VAS. All studies used exercise regularly throughout the month, with some studies asking women not to exercise during menstruation. Given the overall health benefits of exercise, and the relatively low risk of side effects reported in the general population, women may consider using exercise, either alone or in conjunction with other modalities, such as NSAIDs, to manage menstrual pain. It is unclear if the benefits of exercise persist after regular exercise has stopped or if they are similar in women over the age of 25. Further research is required, using validated outcome measures, adequate blinding and suitable comparator groups reflecting current best practice or accounting for the extra attention given during exercise.

Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies

Interim PET-results for prognosis in adults with Hodgkin lymphoma: a systematic review and meta-analysis of prognostic factor studies

Predicting Postoperative Lung Function Following Lung Cancer Resection: A Systematic Review and Meta-analysis

BackgroundLung resection remains the gold standard treatment for early stage lung cancer; prediction of postoperative lung function is a key selection criterion for surgery with the aim of determining risk of postoperative dyspnoea. We aimed to identify the different prediction techniques used, and compare their accuracy. MethodsA systematic review and meta-analysis sought to synthesise studies conducted that assess prediction of postoperative lung function up to 18/02/2018 (n = 135). PROBAST was used to assess risk of bias in studies, 17 studies were judged to be at low risk of bias. FindingsMeta-analysis revealed CT volume and density measurement to be the most accurate (mean difference 71 ml) and precise (standard deviation 207 ml) of the reported techniques used for predicting FEV1; evidence for predicting gas transfer was lacking. InterpretationThe evidence suggests using CT volume and density is the preferred technique in the prediction of postoperative FEV1. Further studies are required to ensure that the methods and thresholds we propose are linked to patient reported outcomes. FundingSalary support for NKO, RM, PN, BN, and AMT was provided by University Hospitals Birmingham NHS Foundation Trust.

Effects of Probiotic Supplement in Pregnant Women with Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background Previous studies showed that probiotics could improve glycemic control and attenuate some of the adverse effects of type 2 diabetes. However, whether the effects are generalizable to gestational diabetes mellitus (GDM) remains uncertain. Objective We conducted a systematic review and meta-analysis to evaluate the effects of probiotic supplement in GDM. Method PubMed, EMBASE, the Cochrane Library, and EBSCO were systematically searched for relevant literature published through January 2019. Randomized controlled trials (RCTs) assessing the effects of probiotic supplement on one or more of the following in GDM were included: pregnancy outcome (the primary outcome), glycemic control, blood lipid profile, and inflammation and oxidative stress. Two reviewers independently extracted data and assessed the risk of bias in studies. Meta-analysis was conducted by using the fixed effects model unless substantial heterogeneity was found among studies. Results Eleven randomized trials involving 719 participants were included for analysis. Eight of the trials were from Iran. Probiotics were given alone in eight trials and synbiotics in three trials. Though the components of probiotics varied, Lactobacillus was included in all trials and Bifidobacterium in all except one. The duration of intervention ranged from 4 to 8 weeks. Almost all trials (10/11) had a low risk of bias. Probiotic supplementation reduced the risk of a newborn's hyperbilirubinemia by 74% and improved four biomarkers for glycemic control (fasting blood glucose, fasting serum insulin, homeostasis model assessment insulin resistance, and quantitative insulin sensitivity check index), two biomarkers for lipid profile (triglycerides and HDL-cholesterol), and four biomarkers for inflammation and oxidative stress (total glutathione, malondialdehyde, nitric oxide, and total antioxidant capacity). But significant heterogeneity was observed in the meta-analyses on the four biomarkers related to glycemic control and on triglycerides, which could not be explained by prespecified subgroup analyses according to the mean age of participants and intervention type (i.e., probiotics or synbiotics). The effects on the risk of preterm delivery, macrosomia and a newborns' hypoglycemia, gestational age, total cholesterol, and LDL-cholesterol were not statistically significant. Conclusion Probiotic supplementation seemed to be able to reduce the risk of a newborn's hyperbilirubinemia and improve glycemic control, blood lipid profiles and inflammation and oxidative stress in pregnant women with GDM. However, due to the heterogeneity among existing studies, the surrogate nature of outcomes, and/or the fact that most studies were from Iran, the clinical significance and generalizability of the above findings remain uncertain. Further studies are warranted to address the limitations of existing evidence and better inform the management of GDM.

Multiple session early psychological interventions for the prevention of post-traumatic stress disorder.

Background The prevention of long-term psychological distress following traumatic events is a major concern. Systematic reviews have suggested that individual Psychological Debriefing is not an effective intervention at preventing post traumatic stress disorder (PTSD). Recently other forms of intervention have been developed with the aim of preventing PTSD. Objectives To examine the efficacy of multiple session early psychological interventions commenced within three months of a traumatic event aimed at preventing PTSD. Single session individual/group psychological interventions were excluded. Search methods Computerised databases were searched systematically, the most recent search was conducted in August 2008. The Journal of Traumatic Stress and the Journal of Consulting and Clinical Psychology were handsearched for the last two years. Personal communication was undertaken with key experts in the field. Selection criteria Randomised controlled trials of any multiple session early psychological intervention or treatment (two or more sessions) designed to prevent symptoms of PTSD. Data collection and analysis Data were entered using Review Manager software. The methodological quality of included studies was assessed individually by two review authors. Data were analysed for summary effects using Review Manager 4.2. Mean difference was used for meta-analysis of continuous outcomes and relative risk for dichotomous outcomes. Main results Eleven studies with a total of 941 participants were found to have evaluated brief psychological interventions aimed at preventing PTSD in individuals exposed to a specific traumatic event, examining a heterogeneous range of interventions. Eight studies were entered into meta-analysis. There was no observable difference between treatment and control conditions on primary outcome measures for these interventions at initial outcome (k=5, n=479; RR 0.84; 95% CI 0.60 to 1.17). There was a trend for increased self-report of PTSD symptoms at 3 to 6 month follow-up in those who received an intervention (k=4, n=292; SMD 0.23; 95% CI 0.00 to 0.46). Two studies compared a memory structuring intervention against supportive listening. There was no evidence supporting the efficacy of this intervention. Authors' conclusions The results suggest that no psychological intervention can be recommended for routine use following traumatic events and that multiple session interventions, like single session interventions, may have an adverse effect on some individuals. The clear practice implication of this is that, at present, multiple session interventions aimed at all individuals exposed to traumatic events should not be used. Further, better designed studies that explore new approaches to early intervention are now required.

Long-term neurocognitive and other side effects of radiotherapy, with or without chemotherapy, for glioma.

Long-term neurocognitive and other side effects of radiotherapy, with or without chemotherapy, for glioma.

A systematic review protocol of timing, efficacy and cost effectiveness of upper limb therapy for motor recovery post-stroke

BackgroundImproving upper limb (UL) motor recovery after stroke represents a major clinical and scientific goal. We aim to complete three systematic reviews to estimate the (1) association between time to start of UL therapy and motor recovery, (2) relative efficacy of different UL therapy approaches post-stroke and (3) cost-effectiveness of UL therapy interventions.MethodsWe have designed a systematic review protocol to address three systematic review questions that were each registered with PROSPERO. The search will be conducted in MEDLINE, EMBASE, and Cochrane Controlled Register of Trials. We will include randomised controlled trials, non-randomised clinical trials, before-after studies and observational studies of adult stroke survivors with an average stroke onset < 6 months, undergoing hospital-based therapy to improve UL function. Eligible interventions will aim to promote UL functional recovery. Two reviewers will independently screen, select and extract data. Study risk of bias will be appraised using appropriate tools. Clinical measures of motor recovery will be investigated (primary measure Fugl Meyer UL assessment), as well as measures of health-related quality of life (primary measure EQ-5D) and all cost-effectiveness analyses completed. Secondary outcomes include therapy dose (minutes, weeks, repetitions as available) and safety (i.e. adverse events, serious adverse events). A narrative synthesis will describe quality and content of the evidence. If feasible, we will conduct random effects meta-analyses where appropriate.DiscussionWe anticipate the findings of this review will increase our understanding of UL therapy and inform the generation of novel, data-driven hypotheses for future UL therapy research post-stroke.Systematic review registrationPROSPERO, http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018019367, http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018111629, http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018111628.

Hospitalisation rates and predictors in people with dementia: a systematic review and meta-analysis

BackgroundHospitalisation is often harmful for people with dementia and results in high societal costs, so avoidance of unnecessary admissions is a global priority. However, no intervention has yet reduced admissions of community-dwelling people with dementia. We therefore aimed to examine hospitalisation rates of people with dementia and whether these differ from people without dementia and to identify socio-demographic and clinical predictors of hospitalisation.MethodsWe searched MEDLINE, Embase, and PsycINFO from inception to 9 May 2019. We included observational studies which (1) examined community-dwelling people with dementia of any age or dementia subtype, (2) diagnosed dementia using validated diagnostic criteria, and (3) examined all-cause general (i.e. non-psychiatric) hospital admissions. Two authors screened abstracts for inclusion and independently extracted data and assessed included studies for risk of bias. Three authors graded evidence strength using Cochrane’s GRADE approach, including assessing for evidence of publication bias using Begg’s test. We used random effects meta-analysis to pool estimates for hospitalisation risk in people with and without dementia.ResultsWe included 34 studies of 277,432 people with dementia: 17 from the USA, 15 from Europe, and 2 from Asia. The pooled relative risk of hospitalisation for people with dementia compared to those without was 1.42 (95% confidence interval 1.21, 1.66) in studies adjusted for age, sex, and physical comorbidity. Hospitalisation rates in people with dementia were between 0.37 and 1.26/person-year in high-quality studies. There was strong evidence that admission is associated with older age, and moderately strong evidence that multimorbidity, polypharmacy, and lower functional ability are associated with admission. There was strong evidence that dementia severity alone is not associated.ConclusionsPeople with dementia are more frequently admitted to hospital than those without dementia, independent of physical comorbidities. Future interventions to reduce unnecessary hospitalisations should target potentially modifiable factors, such as polypharmacy and functional ability, in high-risk populations.

Pregabalin add-on for drug-resistant focal epilepsy.

Epilepsy is a common neurological disease that affects approximately 1% of the UK population. Approximately one-third of these people continue to have seizures despite drug treatment. Pregabalin is one of the newer antiepileptic drugs which have been developed to improve outcomes.This is an updated version of the Cochrane Review published in Issue 3, 2014, and includes three new studies. To assess the efficacy and tolerability of pregabalin when used as an add-on treatment for drug-resistant focal epilepsy. For the latest update we searched the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), on 5 July 2018, MEDLINE (Ovid, 1946 to 5 July 2018), ClinicalTrials.gov (5 July 2018), and the World Health Organization International Clinical Trials Registry Platform (ICTRP, 5 July 2018), and contacted Pfizer Ltd, manufacturer of pregabalin, to identify published, unpublished, and ongoing trials. We included randomised controlled trials comparing pregabalin with placebo or an alternative antiepileptic drug as an add-on for people of any age with drug-resistant focal epilepsy. Double-blind and single-blind trials were eligible for inclusion. The primary outcome was 50% or greater reduction in seizure frequency; secondary outcomes were seizure freedom, treatment withdrawal for any reason, treatment withdrawal due to adverse effects, and proportion of individuals experiencing adverse effects. Two review authors independently selected and assessed trials for eligibility and extracted data. Analyses were by intention-to-treat. We presented results as risk ratios (RR) and odds ratios (OR) with 95% confidence intervals (CIs). Two review authors assessed the included studies for risk of bias using the Cochrane 'Risk of bias' tool. We included nine industry-sponsored randomised controlled trials (3327 participants) in the review. Seven trials compared pregabalin to placebo. For the primary outcome, participants randomised to pregabalin were significantly more likely to attain a 50% or greater reduction in seizure frequency compared to placebo (RR 2.28, 95% CI 1.52 to 3.42, 7 trials, 2193 participants, low-certainty evidence). The odds of response doubled with an increase in dose from 300 mg/day to 600 mg/day (OR 1.99, 95% CI 1.74 to 2.28), indicating a dose-response relationship. Pregabalin was significantly associated with seizure freedom (RR 3.94, 95% CI 1.50 to 10.37, 4 trials, 1125 participants, moderate-certainty evidence). Participants were significantly more likely to withdraw from pregabalin treatment than placebo for any reason (RR 1.35, 95% CI 1.11 to 1.65, 7 trials, 2193 participants, moderate-certainty evidence) and for adverse effects (RR 2.65, 95% CI 1.88 to 3.74, 7 trials, 2193 participants, moderate-certainty evidence).Three trials compared pregabalin to three active-control drugs: lamotrigine, levetiracetam, and gabapentin. Participants allocated to pregabalin were significantly more likely to achieve a 50% or greater reduction in seizure frequency than those allocated to lamotrigine (RR 1.47, 95% CI 1.03 to 2.12, 1 trial, 293 participants) but not those allocated to levetiracetam (RR 0.94, 95% CI 0.80 to 1.11, 1 trial, 509 participants) or gabapentin (RR 0.96, 95% CI 0.82 to 1.12, 1 trial, 484 participants). We found no significant differences between pregabalin and lamotrigine (RR 1.39, 95% CI 0.40 to 4.83) for seizure freedom, however, significantly fewer participants achieved seizure freedom with add-on pregabalin compared to levetiracetam (RR 0.50, 95% CI 0.30 to 0.85). No data were reported for this outcome for pregabalin versus gabapentin. We found no significant differences between pregabalin and lamotrigine (RR 1.07, 95% CI 0.75 to 1.52), levetiracetam (RR 1.03, 95% CI 0.71 to 1.49), or gabapentin (RR 0.78, 95% CI 0.57 to 1.07) for treatment withdrawal due to any reason or due to adverse effects (pregabalin versus lamotrigine: RR 0.89, 95% CI 0.53 to 1.48; versus levetiracetam: RR 1.29, 95% CI 0.66 to 2.54; versus gabapentin: RR 1.07, 95% CI 0.54 to 2.11). Ataxia, dizziness, somnolence, weight gain, and fatigue were significantly associated with pregabalin.We rated the overall risk of bias in the included studies as low or unclear due to the possibility of publication bias and lack of methodological details provided. We rated the certainty of the evidence as very low to moderate using the GRADE approach. Pregabalin, when used as an add-on drug for treatment-resistant focal epilepsy, is significantly more effective than placebo at producing a 50% or greater seizure reduction and seizure freedom. Results demonstrated efficacy for doses from 150 mg/day to 600 mg/day, with increasing effectiveness at 600 mg doses, however issues with tolerability were noted at higher doses. The trials included in this review were of short duration, and longer-term trials are needed to inform clinical decision making.

Epilepsy duration and seizure outcome in epilepsy surgery: A systematic review and meta-analysis.

ObjectiveTo conduct a systematic review and meta-analysis on the effect of earlier or later resective epilepsy surgery on seizure outcome.MethodsWe searched the electronic databases PubMed, EMBASE, and Cochrane Library for studies investigating the association of epilepsy duration and seizure freedom after resective surgery. Two reviewers independently screened citations for eligibility and assessed relevant studies for risk of bias. We combined data in meta-analyses using a random effects model. We assessed the certainty of evidence according to Grading of Recommendations Assessment, Development and Evaluation (GRADE).ResultsTwenty-five studies were included, 12 of which had data suitable for meta-analyses. Comparing seizure outcome if epilepsy surgery was performed before vs after 2, 5, 10, and 20 years of epilepsy duration, and comparing epilepsy duration <5 years to >10 years, we found significant effects favoring shorter duration with risk differences ranging from 0.15 to 0.21 and risk ratios ranging from 1.20 to 1.33 (p < 0.01 for all comparisons). According to GRADE, we found low certainty of evidence favoring shorter epilepsy duration before surgery.ConclusionPeople with shorter epilepsy duration are more likely to be seizure-free at follow-up. Furthermore, there is a positive association between shorter duration and seizure freedom also for very long epilepsy durations. Patients who might benefit from epilepsy surgery should therefore be referred for presurgical assessments without further delay, regardless of epilepsy duration. The low certainty of evidence acknowledges concerns regarding study heterogeneity and possible residual confounding.

Retrieval of individual patient data depended on study characteristics: a randomized controlled trial

ObjectivesThe aim of the study was to examine the effect of providing a financial incentive to authors of randomized clinical trials (RCTs) to obtain individual patient data (IPD). Study Design and SettingParallel-group RCT with authors identified in the RCTs eligible for two systematic reviews. The authors were randomly allocated to the intervention (financial incentive with several contact approaches) or control group (using the same contact approaches). Studied outcomes are proportion of authors who provided IPD, time to obtain IPD, and completeness of IPD received. ResultsOf the 129 authors contacted, 37 authors suggested or contacted a person or funder providing relevant details or showed interest to collaborate, whereas 45 authors directed us to contact a person or funder, lacked resources or time, did not have ownership or approval to share the IPD, or claimed IPD was too old. None of the authors shared their IPD. We contacted 17 sponsors and received two complete IPD datasets from one sponsor. The time to obtain IPD was >1 year after a sponsor's positive response. Common barriers included study identification, data ownership, limited data access, and required IPD licenses. ConclusionIPD sharing may depend on study characteristics, including funding type, study size, study risk of bias, and treatment effect, but not on providing a financial incentive.

The Pharmacologic Management of Osteoporosis in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis

Introduction: Osteoporosis is a common complication of primary biliary cholangitis (PBC) yet evidence for effective therapy is lacking. We sought to review all randomized controlled trials evaluating pharmacotherapy against placebo or no intervention for treatment of osteoporosis in PBC. Methodology: A comprehensive database search was conducted from inception through 29 March 2017. The primary outcome was incidence of fractures; secondary outcomes were change in bone mineral density (BMD) and adverse events. We assessed studies for risk of bias, graded quality of evidence, and used meta-analysis to obtain overall effect by pooling studies of the same drug class. Results: We identified 11 randomized controlled trials evaluating bisphosphonates (3), hormone replacement therapy (2), ursodeoxycholic acid (1), obeticholic acid (1), cyclosporin A (1), vitamin K (1), calcitriol (1), and sodium fluoride (1). No intervention significantly reduced fractures compared to control. Although significant improvement in BMD was seen in one study with alendronate, a third-generation bisphosphonate, no significant improvement was seen on pooled analysis of all bisphosphonates including first-generation bisphosphonates (standard mean difference 0.41, p = 0.68). On pooled analysis, hormone replacement therapy modestly improved lumbar BMD (standard mean difference 0.69, p = 0.02), but with significantly increased adverse events (odds ratio 8.82, p = 0.01). Conclusions: There is a lack of high-quality evidence supporting the efficacy of any treatment of osteoporosis in PBC. This may be explained by lack of power in the included studies. However, our current understanding of PBC-related osteoporosis indicates that it results from decreased bone formation, which may explain the attenuated effect of traditional antiresorptive agents. Future studies should investigate newer anabolic bone agents.

Community participation in health services development, implementation, and evaluation: A systematic review of empowerment, health, community, and process outcomes.

BackgroundCommunity participation is widely believed to be beneficial to the development, implementation and evaluation of health services. However, many challenges to successful and sustainable community involvement remain. Importantly, there is little evidence on the effect of community participation in terms of outcomes at both the community and individual level. Our systematic review seeks to examine the evidence on outcomes of community participation in high and upper-middle income countries.Methods and findingsThis review was developed according to PRISMA guidelines. Eligible studies included those that involved the community, service users, consumers, households, patients, public and their representatives in the development, implementation, and evaluation of health services, policy or interventions. We searched the following databases from January 2000 to September 2016: Medline, Embase, Global Health, Scopus, and LILACs. We independently screened articles for inclusion, conducted data extraction, and assessed studies for risk of bias. No language restrictions were made. 27,232 records were identified, with 23,468 after removal of duplicates. Following titles and abstracts screening, 49 met the inclusion criteria for this review. A narrative synthesis of the findings was conducted. Outcomes were categorised as process outcomes, community outcomes, health outcomes, empowerment and stakeholder perspectives. Our review reports a breadth of evidence that community involvement has a positive impact on health, particularly when substantiated by strong organisational and community processes. This is in line with the notion that participatory approaches and positive outcomes including community empowerment and health improvements do not occur in a linear progression, but instead consists of complex processes influenced by an array of social and cultural factors.ConclusionThis review adds to the evidence base supporting the effectiveness of community participation in yielding positive outcomes at the organizational, community and individual level.Trial registrationProspero record number: CRD42016048244.

Comparative effect of statins and types of physical exercise on arterial stiffness: Protocol for network meta-analysis.

Introduction:The purpose of this study protocol is to provide the methodology for a review to compare the effect of statins vs physical exercise interventions and the effect of different types of physical exercise, on reducing arterial stiffness associated with cardiovascular diseases and mortality.Methods and analysis:The literature search will be conducted in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science databases from their inception until July 31, 2019. We will include randomized controlled trials, nonrandomized experimental studies, and controlled pre–post studies assessing the effect in the general population of statins and physical exercise interventions on arterial stiffness measured by pulse wave velocity. The Cochrane Collaboration's tool and the Quality Assessment Tool for Quantitative Studies will be used to assess the risk of bias for studies included in the systematic review. A Bayesian network meta-analysis will be carried out to determine the comparative effect of the different physical exercise interventions and/or statin intervention.Ethics and dissemination:This study will generate evidence about the effectiveness of both statins and exercise on reducing arterial stiffness that potentially can be transferred to patients and practitioners. Moreover, in light of the importance of reducing arterial stiffness for preventing cardiovascular disease, the evidence provided by this study will be potentially suitable to be included in cardiovascular clinical practice guidelines.Strengths and limitations:This protocol describes the methods of a study examining, using network meta-analysis strategies, the efficacy of statins and different types of exercise on improving arterial stiffness, which is an early marker of atherosclerosis. The results of this study could immediately help clinicians to recommend the best evidence-based intervention to their patients to reduce arterial stiffness and, as a consequence, prevent major complications, such as heart failure, stroke, or myocardial infarction.Trial registration number:PROSPERO CRD42019123120