A systematic review and meta-analysis of interventions to preserve insulin-secreting ß-cell function in people newly diagnosed with type 1 diabetes: Results from intervention studies aimed at improving glucose control.

AIMS: Type 1 diabetes is characterised by the destruction of pancreatic ß-cells. Significant levels of ß-cells remain at diagnosis. Preserving these cells improves glucose control and protects from long-term complications. We undertook a systematic review and meta-analyses of all randomised controlled trials (RCTs) of interventions to preserve ß-cell function in people newly diagnosed with type 1 diabetes. This paper reports the results of interventions for improving glucose control to assess whether they preserve ß-cell function. METHODS: Searches for RCTs in MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov and WHO International Clinical Trials Registry. Eligible studies included newly diagnosed patients with type 1 diabetes, any intervention to improve glucose control and at least 1 month of follow-up. Data were extracted using a pre-defined data-extraction sheet with 10% of extractions checked by a second reviewer. RESULTS: Twenty-eight studies with 1662 participants were grouped by intervention into six subgroups (alternative insulins, subcutaneous and intravenous insulin delivery, intensive therapy, glucose sensing, adjuncts). Only three studies demonstrated an improvement in glucose control as well as ß-cell function. These interventions included intensive insulin therapy and use of an alternative insulin. CONCLUSIONS: This is the largest comprehensive review of RCTs in this area. It demonstrates a lack of robust evidence that interventions to improve glucose control preserve ß-cell function in new onset type 1 diabetes, although analysis was hampered by low-quality evidence and inconsistent reporting of studies. Development of guidelines to support the design of trials in this field is a priority.

Botulinum toxins for the prevention of migraine in adults.

BACKGROUND: Migraine occurs in around 15% of adults and is ranked as the seventh most disabling disease amongst all diseases globally. Despite the available treatments many people suffer prolonged and frequent attacks which have a major impact on their quality of life. Chronic migraine is defined as 15 or more days of headache per month, at least eight of those days being migraine. People with episodic migraine have fewer than 15 headache days per month. Botulinum toxin type A has been licensed in some countries for chronic migraine treatment, due to the results of just two trials. OBJECTIVES: To assess the effects of botulinum toxins versus placebo or active treatment for the prevention or reduction in frequency of chronic or episodic migraine in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE & MEDLINE in Process, Embase, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry (to December 2017). We examined reference lists and carried out citation searches on key publications. We sent correspondence to major manufacturers of botulinum toxin. SELECTION CRITERIA: Randomised, double-blind, controlled trials of botulinum toxin (any sero-type) injections into the head and neck for prophylaxis of chronic or episodic migraine in adults. Eligible comparators were placebo, alternative prophylactic agent or different dose of botulinum toxin. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and extracted data. For continuous outcomes we used mean change data when available. For dichotomous data we calculated risk ratios (RRs). We used data from the 12-week post-treatment follow-up time point. We assessed the evidence using GRADE and created two 'Summary of findings' tables. MAIN RESULTS: Description of trialsWe found 90 articles describing 28 trials (4190 participants), which were eligible for inclusion. The longest treatment duration was three rounds of injections with three months between treatments, so we could not analyse long-term effects. For the primary analyses, we pooled data from both chronic and episodic participant populations. Where possible, we also separated data into chronic migraine, episodic migraine and 'mixed group' classification subgroups. Most trials (21 out of 28) were small (fewer than 50 participants per trial arm). The risk of bias for included trials was low or unclear across most domains, with some trials reporting a high risk of bias for incomplete outcome data and selective outcome reporting.Botulinum toxin versus placeboTwenty-three trials compared botulinum toxin with placebo. Botulinum toxin may reduce the number of migraine days per month in the chronic migraine population by 3.1 days (95% confidence interval (CI) -4.7 to -1.4, 4 trials, 1497 participants, low-quality evidence). This was reduced to -2 days (95% CI -2.8 to -1.1, 2 trials, 1384 participants; moderate-quality evidence) when we removed small trials.A single trial of people with episodic migraine (N = 418) showed no difference between groups for this outcome measure (P = 0.49).In the chronic migraine population, botulinum toxin reduces the number of headache days per month by 1.9 days (95% CI -2.7 to -1.0, 2 trials, 1384 participants, high-quality evidence). We did not find evidence of a difference in the number of migraine attacks for both chronic and episodic migraine participants (6 trials, N = 2004, P = 0.30, low-quality evidence). For the population of both chronic and episodic migraine participants a reduction in severity of migraine rated during clinical visits, on a 10 cm visual analogue scale (VAS) of 3.3 cm (95% CI -4.2 to -2.5, very low-quality evidence) in favour of botulinum toxin treatment came from four small trials (N = 209); better reporting of this outcome measure from the additional eight trials that recorded it may have improved our confidence in the pooled estimate. Global assessment and quality-of-life measures were poorly reported and it was not possible to carry out statistical analysis of these outcome measures. Analysis of adverse events showed an increase in the risk ratio with treatment with botulinum toxin over placebo 30% (RR 1.28, 95% CI 1.12 to 1.47, moderate-quality evidence). For every 100 participants 60 experienced an adverse event in the botulinum toxin group compared with 47 in the placebo group.Botulinum toxin versus other prophylactic agentThree trials studied comparisons with alternative oral prophylactic medications. Meta-analyses were not possible for number of migraine days, number of headache days or number of migraine attacks due to insufficient data, but individually trials reported no differences between groups for a variety of efficacy measures in the population of both chronic and episodic migraine participants. The global impression of disease measured using Migraine Disability Assessment (MIDAS) scores were reported from two trials that showed no difference between groups. Compared with oral treatments, botulinum toxin showed no between-group difference in the risk of adverse events (2 trials, N = 114, very low-quality evidence). The relative risk reduction (RRR) for withdrawing from botulinum toxin due to adverse events compared with the alternative prophylactic agent was 72% (P = 0.02, 2 trials, N = 119).Dosing trialsThere were insufficient data available for the comparison of different doses.Quality of the evidenceThe quality of the evidence assessed using GRADE methods was varied but mostly very low; the quality of the evidence for the placebo and active control comparisons was low and very low, respectively for the primary outcome measure. Small trial size, high risk of bias and unexplained heterogeneity were common reasons for downgrading the quality of the evidence. AUTHORS' CONCLUSIONS: In chronic migraine, botulinum toxin type A may reduce the number of migraine days per month by 2 days compared with placebo treatment. Non-serious adverse events were probably experienced by 60/100 participants in the treated group compared with 47/100 in the placebo group. For people with episodic migraine, we remain uncertain whether or not this treatment is effective because the quality of this limited evidence is very low. Better reporting of outcome measures in published trials would provide a more complete evidence base on which to draw conclusions.

Physiotherapy for Parkinson's disease: a comparison of techniques.

BACKGROUND: Despite medical therapies and surgical interventions for Parkinson's disease (PD), patients develop progressive disability. The role of physiotherapy is to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. The overall aim is to optimise independence, safety and wellbeing, thereby enhancing quality of life. Trials have shown that physiotherapy has short-term benefits in PD. However, which physiotherapy intervention is most effective remains unclear. OBJECTIVES: To assess the effectiveness of one physiotherapy intervention compared with a second approach in patients with PD. SEARCH METHODS: Relevant trials were identified by electronic searches of numerous literature databases (for example MEDLINE, EMBASE) and trial registers, plus handsearching of major journals, abstract books, conference proceedings and reference lists of retrieved publications. The literature search included trials published up to the end of January 2012. SELECTION CRITERIA: Randomised controlled trials of one physiotherapy intervention versus another physiotherapy intervention in patients with PD. DATA COLLECTION AND ANALYSIS: Data were abstracted independently from each paper by two authors. Trials were classified into the following intervention comparisons: general physiotherapy, exercise, treadmill training, cueing, dance and martial arts. MAIN RESULTS: A total of 43 trials were identified with 1673 participants. All trials used small patient numbers (average trial size of 39 participants); the methods of randomisation and concealment of allocation were poor or not stated in most trials. Blinded assessors were used in just over half of the trials and only 10 stated that they used intention-to-treat analysis.A wide variety of validated and customised outcome measures were used to assess the effectiveness of physiotherapy interventions. The most frequently reported physiotherapy outcomes were gait speed and timed up and go, in 19 and 15 trials respectively. Only five of the 43 trials reported data on falls (12%). The motor subscales of the Unified Parkinson's Disease Rating Scale and Parkinson's Disease Questionnaire-39 were the most commonly reported clinician-rated disability and patient-rated quality of life outcome measures, used in 22 and 13 trials respectively. The content and delivery of the physiotherapy interventions varied widely in the trials included within this review, so no quantitative meta-analysis could be performed. AUTHORS' CONCLUSIONS: Considering the small number of participants examined, the methodological flaws in many of the studies, the possibility of publication bias, and the variety of interventions, formal comparison of the different physiotherapy techniques could not be performed. There is insufficient evidence to support or refute the effectiveness of one physiotherapy intervention over another in PD.This review shows that a wide range of physiotherapy interventions to treat PD have been tested . There is a need for more specific trials with improved treatment strategies to underpin the most appropriate choice of physiotherapy intervention and the outcomes measured.

Physiotherapy versus placebo or no intervention in Parkinson's disease.

BACKGROUND: Despite medical therapies and surgical interventions for Parkinson's disease (PD), patients develop progressive disability. Physiotherapy aims to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. The overall aim is to optimise independence, safety, and well-being, thereby enhancing quality of life. OBJECTIVES: To assess the effectiveness of physiotherapy intervention compared with no intervention in patients with PD. SEARCH METHODS: We identified relevant trials by conducting electronic searches of numerous literature databases (e.g. MEDLINE, EMBASE) and trial registers, and by handsearching major journals, abstract books, conference proceedings, and reference lists of retrieved publications. The literature search included trials published up to the end of January 2012. SELECTION CRITERIA: Randomised controlled trials of physiotherapy intervention versus no physiotherapy intervention in patients with PD. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from each article. We used standard meta-analysis methods to assess the effectiveness of physiotherapy intervention compared with no physiotherapy intervention. Trials were classified into the following intervention comparisons: general physiotherapy, exercise, treadmill training, cueing, dance, and martial arts. We used tests for heterogeneity to assess for differences in treatment effect across these different physiotherapy interventions. MAIN RESULTS: We identified 39 trials with 1827 participants. We considered the trials to be at a mixed risk of bias as the result of unreported allocation concealment and probable detection bias. Compared with no intervention, physiotherapy significantly improved the gait outcomes of speed (mean difference 0.04 m/s, 95% confidence interval (CI) 0.02 to 0.06, P = 0.0002); two- or six-minute walk test (13.37 m, 95% CI 0.55 to 26.20, P = 0.04) and Freezing of Gait questionnaire (-1.41, 95% CI -2.63 to -0.19, P = 0.02); functional mobility and balance outcomes of Timed Up & Go test (-0.63 s, 95% CI -1.05 to -0.21, P = 0.003), Functional Reach Test (2.16 cm, 95% CI 0.89 to 3.43, P = 0.0008), and Berg Balance Scale (3.71 points, 95% CI 2.30 to 5.11, P < 0.00001); and clinician-rated disability using the Unified Parkinson's Disease Rating Scale (UPDRS) (total -6.15 points, 95% CI-8.57 to -3.73, P < 0.00001; activities of daily living: -1.36, 95% CI -2.41 to -0.30, P = 0.01; and motor: -5.01, 95% CI -6.30 to -3.72, P < 0.00001). No difference between arms was noted in falls (Falls Efficacy Scale: -1.91 points, 95% CI -4.76 to 0.94, P = 0.19) or patient-rated quality of life (PDQ-39 Summary Index: -0.38 points, 95% CI -2.58 to 1.81, P = 0.73). One study reported that adverse events were rare; no other studies reported data on this outcome. Indirect comparisons of the different physiotherapy interventions revealed no evidence that the treatment effect differed across physiotherapy interventions for any of the outcomes assessed. AUTHORS' CONCLUSIONS: Benefit for physiotherapy was found in most outcomes over the short term (i.e. < 3 months) but was significant only for speed, two- or six-minute walk test, Freezing of Gait questionnaire, Timed Up & Go, Functional Reach Test, Berg Balance Scale, and clinician-rated UPDRS. Most of the observed differences between treatments were small. However, for some outcomes (e.g. speed, Berg Balance Scale, UPDRS), the differences observed were at, or approaching, what are considered minimal clinically important changes. These benefits should be interpreted with caution because the quality of most of the included trials was not high. Variation in measurements of outcome between studies meant that our analyses include a small proportion of the participants recruited.This review illustrates that a wide range of approaches are employed by physiotherapists to treat patients with PD. However, no evidence of differences in treatment effect was noted between the different types of physiotherapy interventions being used, although this was based on indirect comparisons. A consensus menu of 'best practice' physiotherapy is needed, as are large, well-designed randomised controlled trials undertaken to demonstrate the longer-term efficacy and cost-effectiveness of 'best practice' physiotherapy in PD.

Evaluation of court-initiated randomized controlled trial of online parent programs for divorcing and separating parents.

We conducted an evaluation of a court-initiated randomized controlled trial comparing outcomes for parents assigned to either a no-program control group or one of two online parenting programs-Two Families Now (TFN) or Children in Between (CIB)-among 221 parents in initial divorce or separation court cases. We gathered parent report measures of family functioning at study entry, completion of program, and 1-year following study entry. We also gathered and coded court records to capture the content of the document resolving issues and occurrence of relitigation in the following year. All findings became statistically nonsignificant when a Bonferroni correction was employed. Before correction, however, a few statistically significant differences between groups emerged. Immediately following program completion, there were no study condition differences on measures of parental beliefs and intentions regarding parenting. One year following study entry, three statistically significant differences between program and no-program conditions emerged. Those assigned to a program reported significantly less intimate partner abuse and had less relitigation in court than those in the no-program condition, both with small effect sizes. Contrary to hypotheses, parents assigned to a program reported less social support than parents in the no-program condition. Overall, the findings do not provide strong support for the two investigated brief online parenting programs, demonstrating the need for continued rigorous evaluation of online parenting programs for divorcing and separating parents. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Speech and language therapy versus placebo or no intervention for speech problems in Parkinson's disease.

BACKGROUND: Parkinson's disease patients commonly suffer from speech and vocal problems including dysarthric speech, reduced loudness and loss of articulation. These symptoms increase in frequency and intensity with progression of the disease). Speech and language therapy (SLT) aims to improve the intelligibility of speech with behavioural treatment techniques or instrumental aids. OBJECTIVES: To compare the efficacy of speech and language therapy versus placebo or no intervention for speech and voice problems in patients with Parkinson's disease. SEARCH METHODS: Relevant trials were identified by electronic searches of numerous literature databases including MEDLINE, EMBASE, and CINAHL, as well as handsearching of relevant conference abstracts and examination of reference lists in identified studies and other reviews. The literature search included trials published prior to 11(th) April 2011. SELECTION CRITERIA: Only randomised controlled trials (RCT) of speech and language therapy versus placebo or no intervention were included. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by CH and CT and differences settled by discussion. MAIN RESULTS: Three randomised controlled trials with a total of 63 participants were found comparing SLT with placebo for speech disorders in Parkinson's disease. Data were available from 41 participants in two trials. Vocal loudness for reading a passage increased by 6.3 dB (P = 0.0007) in one trial, and 11.0 dB (P = 0.0002) in another trial. An increase was also seen in both of these trials for monologue speaking of 5.4 dB (P = 0.002) and 11.0 dB (P = 0.0002), respectively. It is likely that these are clinically significant improvements. After six months, patients from the first trial were still showing a statistically significant increase of 4.5 dB (P = 0.0007) for reading and 3.5 dB for monologue speaking. Some measures of speech monotoni city and articulation were investigated; however, all these results were non-significant. AUTHORS' CONCLUSIONS: Although improvements in speech impairments were noted in these studies, due to the small number of patients examined, methodological flaws, and the possibility of publication bias, there is insufficient evidence to conclusively support or refute the efficacy of SLT for speech problems in Parkinson's disease. A large well designed placebo-controlled RCT is needed to demonstrate SLT's effectiveness in Parkinson's disease. The trial should conform to CONSORT guidelines. Outcome measures with particular relevance to patients with Parkinson's disease should be chosen and patients followed for at least six months to determine the duration of any improvement.

Comparison of speech and language therapy techniques for speech problems in Parkinson's disease.

BACKGROUND: Patients with Parkinson's disease commonly suffer from speech and voice difficulties such as impaired articulation and reduced loudness. Speech and language therapy (SLT) aims to improve the intelligibility of speech with behavioural treatment techniques or instrumental aids. OBJECTIVES: To compare the efficacy and effectiveness of novel SLT techniques versus a standard SLT approach to treat Parkinsonian speech problems. SEARCH METHODS: We identified relevant, published prior to 11(th) April 2011, by electronic searches of numerous literature databases including CENTRAL, MEDLINE and CINAHL, as well as handsearching relevant conference abstracts and examining reference lists in identified studies and other reviews. SELECTION CRITERIA: Only randomised controlled trials (RCT) of one type of speech and language therapy versus another were included. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and resolved differences by discussion. MAIN RESULTS: Six trials involving 159 patients satisfied the inclusion criteria. Data could not be analysed from one trial due to changes in patient numbers and from a second because the data provided were not in a usable format. All trials reported intelligibility measures but a statistically significant result was only reported for the diagnostic rhyme test used in the study of Lee Silverman Voice Treatment -LOUD (LSVT-LOUD) versus a modified version of this therapy (LSVT-ARTIC). In this case a difference of 12.5 points (95% confidence interval (CI) -22.2 to -2.8; P = 0.01) between the mean changes in favour of the LSVT-LOUD group was reported for a speech sample overlaid with Babble noise; this difference was not reproduced for the two additional noise conditions under which the speech samples were assessed. LSVT-LOUD also outperformed LSVT-ARTIC and Respiration therapy (RT) in improving loudness, with a difference in reading a sample text of 5.0 dB (95%CI -8.3 to -1.7; P = 0.003) and 5.5 dB (95% CI 3.4 to 7.7; P < 0.00001) respectively, and a difference in monologue speech of 2.9 dB (95% CI 0.6 to 5.2; P = 0.01) versus RT. AUTHORS' CONCLUSIONS: Considering the small patient numbers in these trials, there is insufficient evidence to support or refute the efficacy of any form of SLT over another to treat speech problems in patients with Parkinson's disease.

Physiotherapy versus placebo or no intervention in Parkinson's disease.

BACKGROUND: Despite medical therapies and surgical interventions for Parkinson's disease (PD), patients develop progressive disability. The role of physiotherapy aims to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. The overall aim is to optimise independence, safety and well-being, thereby enhancing quality of life. OBJECTIVES: To assess the effectiveness of physiotherapy intervention compared with no intervention in patients with PD. SEARCH METHODS: We identified relevant trials by electronic searches of numerous literature databases (e.g. MEDLINE, EMBASE) and trial registers, plus handsearching of major journals, abstract books, conference proceedings and reference lists of retrieved publications. The literature search included trials published up to end of December 2010. SELECTION CRITERIA: Randomised controlled trials of physiotherapy intervention versus no physiotherapy intervention in patients with PD. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from each article. We used standard meta-analysis methods to assess the effectiveness of physiotherapy intervention compared with no physiotherapy intervention. Trials were classified into the following intervention comparisons: general physiotherapy, exercise, treadmill training, cueing, dance and martial arts. We used tests for heterogeneity to assess for differences in treatment effect across these different physiotherapy interventions. MAIN RESULTS: We identified 33 trials with 1518 participants. Compared with no-intervention, physiotherapy significantly improved the gait outcomes of velocity (mean difference 0.05 m/s, 95% confidence interval (CI): 0.02 to 0.07, P = 0.0002), two- or six-minute walk test (16.40 m, CI: 1.90 to 30.90, P = 0.03) and step length (0.03 m, CI: 0 to 0.06, P = 0.04); functional mobility and balance outcomes of Timed Up & Go test (-0.61 s, CI: -1.06 to -0.17, P = 0.006), Functional Reach Test (2.16 cm, CI: 0.89 to 3.43, P = 0.0008) and Berg Balance Scale (3.36 points, CI: 1.91 to 4.81, P < 0.00001); and clinician-rated disability using the Unified Parkinson's Disease Rating Scale (UPDRS) (total: -4.46 points, CI -7.16 to -1.75, P = 0.001; activities of daily living: -1.36, CI -2.41 to -0.30, P = 0.01; and motor: -4.09, CI: -5.59 to -2.59, P < 0.00001). There was no difference between arms in falls or patient-rated quality of life. Indirect comparisons of the different physiotherapy interventions found no evidence that the treatment effect differed across the physiotherapy interventions for any of the outcomes assessed. AUTHORS' CONCLUSIONS: Benefit for physiotherapy was found in most outcomes over the short-term (i.e. < three months), but was only significant for velocity, two- or six-minute walk test, step length, Timed Up & Go, Functional Reach Test, Berg Balance Scale and clinician-rated UPDRS. Most of the observed differences between the treatments were small. However, for some outcomes (e.g. velocity, Berg Balance Scale and UPDRS), the differences observed were at, or approaching, what are considered minimally clinical important changes.The review illustrates that a wide range of approaches are employed by physiotherapists to treat PD. However, there was no evidence of differences in treatment effect between the different types of physiotherapy interventions being used, though this was based on indirect comparisons. There is a need to develop a consensus menu of 'best-practice' physiotherapy, and to perform large well-designed randomised controlled trials to demonstrate the longer-term efficacy and cost-effectiveness of 'best practice' physiotherapy in PD.

Physiotherapy versus placebo or no intervention in Parkinson's disease.

BACKGROUND: Despite medical therapies and surgical interventions for Parkinson's disease (PD), patients develop progressive disability. The role of physiotherapy aims to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. The overall aim is to optimise independence, safety and well-being, thereby enhancing quality of life. OBJECTIVES: To assess the effectiveness of physiotherapy intervention compared with no intervention in patients with PD. SEARCH METHODS: We identified relevant trials by electronic searches of numerous literature databases (e.g. MEDLINE, EMBASE) and trial registers, plus handsearching of major journals, abstract books, conference proceedings and reference lists of retrieved publications. The literature search included trials published up to end of December 2010. SELECTION CRITERIA: Randomised controlled trials of physiotherapy intervention versus no physiotherapy intervention in patients with PD. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from each article. We used standard meta-analysis methods to assess the effectiveness of physiotherapy intervention compared with no physiotherapy intervention. Trials were classified into the following intervention comparisons: general physiotherapy, exercise, treadmill training, cueing, dance and martial arts. We used tests for heterogeneity to assess for differences in treatment effect across these different physiotherapy interventions. MAIN RESULTS: We identified 33 trials with 1518 participants. Compared with no-intervention, physiotherapy significantly improved the gait outcomes of velocity (mean difference 0.05 m/s, 95% confidence interval (CI): 0.02 to 0.07, P = 0.0002), two- or six-minute walk test (16.40 m, CI: 1.90 to 30.90, P = 0.03) and step length (0.03 m, CI: 0 to 0.06, P = 0.04); functional mobility and balance outcomes of Timed Up & Go test (-0.61 s, CI: -1.06 to -0.17, P = 0.006), Functional Reach Test (2.16 cm, CI: 0.89 to 3.43, P = 0.0008) and Berg Balance Scale (3.36 points, CI: 1.91 to 4.81, P < 0.00001); and clinician-rated disability using the Unified Parkinson's Disease Rating Scale (UPDRS) (total: -4.46 points, CI -7.16 to -1.75, P = 0.001; activities of daily living: -1.36, CI -2.41 to -0.30, P = 0.01; and motor: -4.09, CI: -5.59 to -2.59, P < 0.00001). There was no difference between arms in falls or patient-rated quality of life. Indirect comparisons of the different physiotherapy interventions found no evidence that the treatment effect differed across the physiotherapy interventions for any of the outcomes assessed. AUTHORS' CONCLUSIONS: Benefit for physiotherapy was found in most outcomes over the short-term (i.e. < three months), but was only significant for velocity, two- or six-minute walk test, step length, Timed Up & Go, Functional Reach Test, Berg Balance Scale and clinician-rated UPDRS. Most of the observed differences between the treatments were small. However, for some outcomes (e.g. velocity, Berg Balance Scale and UPDRS), the differences observed were at, or approaching, what are considered minimally clinical important changes.The review illustrates that a wide range of approaches are employed by physiotherapists to treat PD. However, there was no evidence of differences in treatment effect between the different types of physiotherapy interventions being used, though this was based on indirect comparisons. There is a need to develop a consensus menu of 'best-practice' physiotherapy, and to perform large well-designed randomised controlled trials to demonstrate the longer-term efficacy and cost-effectiveness of 'best practice' physiotherapy in PD.

Lessons for a COVID-19 era: Barriers and facilitators to court ordered online parenting programs for divorcing and separating parents.

Family courts are increasingly interested in online parenting programs for divorcing and separating parents, particularly during the COVID-19 pandemic. To our knowledge, no previous study has evaluated the barriers to and facilitators of parent participation in these programs for family law cases. We interviewed 61 parents in the midst of family law cases regarding their perspectives. While many parents viewed online parent programs positively (e.g., convenient), they also reported barriers to participation (e.g., technology problems). We offer recommendations (e.g., communication about program benefits) to support courts as they decide whether to continue ordering online parent programs following the pandemic.

Systematic review of levodopa dose equivalency reporting in Parkinson's disease.

Interpretation of clinical trials comparing different drug regimens for Parkinson's disease (PD) is complicated by the different dose intensities used: higher doses of levodopa and, possibly, other drugs produce better symptomatic control but more late complications. To address this problem, conversion factors have been calculated for antiparkinsonian drugs that yield a total daily levodopa equivalent dose (LED). LED estimates vary, so we undertook a systematic review of studies reporting LEDs to provide standardized formulae. Electronic database and hand searching of references identified 56 primary reports of LED estimates. Data were extracted and the mean and modal LEDs calculated. This yielded a standardized LED for each drug, providing a useful tool to express dose intensity of different antiparkinsonian drug regimens on a single scale. Using these conversion formulae to report LEDs would improve the consistency of reporting and assist the interpretation of clinical trials comparing different PD medications.

Impact of obstetric unit closures, travel time and distance to obstetric services on maternal and neonatal outcomes in high-income countries: a systematic review.

OBJECTIVES: To systematically review (1) The effect of obstetric unit (OU) closures on maternal and neonatal outcomes and (2) The association between travel distance/time to an OU and maternal and neonatal outcomes. DESIGN: Systematic review of any quantitative studies with a comparison group. DATA SOURCES: Embase, MEDLINE, PsycINFO, Applied Social Science Index and Abstracts, Cumulative Index to Nursing and Allied Health and grey literature were searched. METHODS: Eligible studies explored the impact of closure of an OU or the effect of travel distance/time on prespecified maternal or neonatal outcomes. Only studies of women giving birth in high-income countries with universal health coverage of maternity services comparable to the UK were included. Identification of studies, extraction of data and risk of bias assessment were undertaken by at least two reviewers independently. The risk of bias checklist was based on the Cochrane Effective Practice and Organisation of Care criteria and the Newcastle-Ottawa scale. Heterogeneity across studies precluded meta-analysis and synthesis was narrative, with key findings tabulated. RESULTS: 31 studies met the inclusion criteria. There was some evidence to suggest an increase in babies born before arrival following OU closures and/or associated with longer travel distances or time. This may be associated with an increased risk of perinatal or neonatal mortality, but this finding was not consistent across studies. Evidence on other maternal and neonatal outcomes was limited but did not suggest worse outcomes after closures or with longer travel times/distances. Interpretation of findings for some studies was hampered by concerns around how accurately exposures were measured, and/or a lack of adjustment for confounders or temporal changes. CONCLUSION: It is not possible to conclude from this review whether OU closure, increased travel distances or times are associated with worse outcomes for the mother or the baby. PROSPERO REGISTRATION NUMBER: CRD42017078503.

Cochrane systematic review and meta-analysis of botulinum toxin for the prevention of migraine.

OBJECTIVES: To assess the effects of botulinum toxin for prevention of migraine in adults. DESIGN: Systematic review and meta-analysis. DATA SOURCES: CENTRAL, MEDLINE, Embase and trial registries. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) of botulinum toxin compared with placebo, active treatment or clinically relevant different dose for adults with chronic or episodic migraine, with or without the additional diagnosis of medication overuse headache. DATA EXTRACTION AND SYNTHESIS: Cochrane methods were used to review double-blind RCTs. Twelve week post-treatment time-point data was analysed. RESULTS: Twenty-eight trials (n=4190) were included. Trial quality was mixed. Botulinum toxin treatment resulted in reduced frequency of -2.0 migraine days/month (95% CI -2.8 to -1.1, n=1384) in chronic migraineurs compared with placebo. An improvement was seen in migraine severity, measured on a numerical rating scale 0 to 10 with 10 being maximal pain, of -2.70 cm (95% CI -3.31 to -2.09, n=75) and -4.9 cm (95% CI -6.56 to -3.24, n=32) for chronic and episodic migraine respectively. Botulinum toxin had a relative risk of treatment related adverse events twice that of placebo, but a reduced risk compared with active comparators (relative risk 0.76, 95% CI 0.59 to 0.98) and a low withdrawal rate (3%). Although individual trials reported non-inferiority to oral treatments, insufficient data were available for meta-analysis of effectiveness outcomes. CONCLUSIONS: In chronic migraine, botulinum toxin reduces migraine frequency by 2 days/month and has a favourable safety profile. Inclusion of medication overuse headache does not preclude its effectiveness. Evidence to support or refute efficacy in episodic migraine was not identified.

A systematic review of epigenetic biomarkers in progression from non-dysplastic Barrett's oesophagus to oesophageal adenocarcinoma.

OBJECTIVES: The objective of this systematic review is to identify and summarise studies which examine epigenetic biomarkers in patients with Barrett's oesophagus (BO) and their association with progression to oesophageal adenocarcinoma (OADC). BO is a precursor lesion for OADC. There is no clinical test to predict patients who are likely to progress to OADC. An epigenetic biomarker could predict patients who are at high risk of progression from BO to OADC which could facilitate earlier diagnosis and spare those unlikely to develop cancer from regular invasive surveillance endoscopy. SETTING: A systematic search was conducted of the following databases: MEDLINE, MEDLINE in Process, EMBASE, Cochrane Central, ISI Conference Proceedings Citation Index and the British Library's ZETOC. Studies were conducted in secondary and tertiary care settings. PARTICIPANTS: All studies measuring epigenetic change in patients over 18 years old who progressed from non-dysplastic BO to OADC were included. Genetic, in vitro and studies which did not measure progression in the same patient cohort were excluded. Study inclusion and risk of bias of individual eligible studies were assessed in duplicate by two reviewers using a modified Quality in Prognostic Studies tool. RESULTS: 14 studies met the inclusion criteria. 42 epigenetic markers were identified, and 5 studies developed models aiming to predict progression to OADC. CONCLUSIONS: The evidence from this systematic review is suggestive of a role for p16 as an epigenetic biomarker for the progression of BO to OADC. PROSPERO NUMBER: CRD42016038654.

Clinical effectiveness of cell therapies in patients with chronic liver disease and acute-on-chronic liver failure: a systematic review protocol.

BACKGROUND: Chronic liver disease (CLD) is a major health burden worldwide. Liver cirrhosis, a form of CLD is the fifth most common cause of death in the UK. Acute-on-chronic liver failure (ACLF) is the result of an acute insult superimposed on patients with liver cirrhosis as a result of precipitating events such as infection or bleeding. ACLF has a high associated mortality as a result of multi-organ failure. The only effective treatment for CLD is liver transplantation, but the treatment is limited by shortage of donor organs. As a result, alternative treatments such as cell therapies have been studied in patients with liver diseases. This study will systematically review the evidence on clinical effectiveness of cell therapies in patients. METHODS: All types of study design that investigate the effectiveness of cell therapies (haematopoietic, mesenchymal and unsorted cell types) of autologous or allogeneic origin and/or the use of granulocyte colony-stimulating factor in patients with CLD including ACLF will be included (except case reports). Both autologous and allogenic cell types will be included. The primary outcomes of interest are survival, model for end-stage liver disease score, quality of life and adverse events. Secondary outcomes include liver function tests, Child-Pugh score and events of liver decompensation. A literature search will be conducted in the following databases: MEDLINE, MEDLINE in Process, EMBASE and Cochrane Library (CENTRAL, CDSR, DARE, HTA databases). Trial registers will be searched for ongoing trials, as will conference proceedings. Reference lists of relevant articles and systematic reviews will be screened. Randomised controlled trial (RCT) evidence is likely to be scant; therefore, controlled trials and concurrently controlled observational studies will be primarily analysed and uncontrolled observational studies will be analysed where primary outcomes are not reported in the control studies or where uncontrolled studies have longer follow-up. Initial screening of studies will be carried by one reviewer with a proportion checked by another reviewer. Full-text selection will be performed by two reviewers independently against the pre-defined selection criteria. The data collection and the risk of bias assessment will be completed by one reviewer and counter checked by another reviewer for all selected studies. Where appropriate, data will be meta-analysed for each study design, therapy and outcome. Data specifically on ACLF will be treated as a subgroup. DISCUSSION: This systematic review will identify the available evidence on the effectiveness of cell therapies in patients with CLD and in ACLF subgroup. The findings will aid decision-making by clinicians and health service leaders. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016016104.

Physiotherapy intervention in Parkinson's disease: systematic review and meta-analysis.

OBJECTIVE: To assess the effectiveness of physiotherapy compared with no intervention in patients with Parkinson's disease. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Literature databases, trial registries, journals, abstract books, and conference proceedings, and reference lists, searched up to the end of January 2012. REVIEW METHODS: Randomised controlled trials comparing physiotherapy with no intervention in patients with Parkinson's disease were eligible. Two authors independently abstracted data from each trial. Standard meta-analysis methods were used to assess the effectiveness of physiotherapy compared with no intervention. Tests for heterogeneity were used to assess for differences in treatment effect across different physiotherapy interventions used. Outcome measures were gait, functional mobility and balance, falls, clinician rated impairment and disability measures, patient rated quality of life, adverse events, compliance, and economic analysis outcomes. RESULTS: 39 trials of 1827 participants met the inclusion criteria, of which 29 trials provided data for the meta-analyses. Significant benefit from physiotherapy was reported for nine of 18 outcomes assessed. Outcomes which may be clinically significant were speed (0.04 m/s, 95% confidence interval 0.02 to 0.06, P<0.001), Berg balance scale (3.71 points, 2.30 to 5.11, P<0.001), and scores on the unified Parkinson's disease rating scale (total score -6.15 points, -8.57 to -3.73, P<0.001; activities of daily living subscore -1.36, -2.41 to -0.30, P=0.01; motor subscore -5.01, -6.30 to -3.72, P<0.001). Indirect comparisons of the different physiotherapy interventions found no evidence that the treatment effect differed across the interventions for any outcomes assessed, apart from motor subscores on the unified Parkinson's disease rating scale (in which one trial was found to be the cause of the heterogeneity). CONCLUSIONS: Physiotherapy has short term benefits in Parkinson's disease. A wide range of physiotherapy techniques are currently used to treat Parkinson's disease, with little difference in treatment effects. Large, well designed, randomised controlled trials with improved methodology and reporting are needed to assess the efficacy and cost effectiveness of physiotherapy for treating Parkinson's disease in the longer term.