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This study provides an overview of the relationships between exposure to work-related hand-arm vibration and the occurrence of pre-defined disorders of the hands. We searched Medline, Embase, Web of Science, Cochrane Central, and PsycINFO for cross-sectional and longitudinal studies on the association between work-related vibration exposure and the occurrence of hand-arm vibration syndrome (including vibration-induced white finger), Dupuytren’s contracture, or hypothenar hammer syndrome. We used a 16-item checklist for assessing the risk of bias. We present results narratively, and we conducted random effects meta-analyses if possible. We included 10 studies with more than 24,381 participants. Our results showed statistically significant associations between the exposure to hand-arm vibrations and the occurrence of the selected disorders, with pooled odds ratios ranging between 1.35 (95% CI: 1.28 to 2.80) and 3.43 (95% CI: 2.10 to 5.59). Considerable between-study heterogeneity was observed. Our analyses show that exposure to vibrating tools at work is associated with an increased risk for the occurrence of selected disorders of the hands. Due to the majority of studies being cross-sectional, no firm conclusion is possible regarding causal relationships between vibration exposure and disorder occurrence. Future research should specifically address whether reducing exposure to hand-held vibrating tools at work reduces the incidence of the disorders of the hands investigated in this systematic review.

This systematic review updates a previous systematic review on work-related physical and psychosocial risk factors for elbow disorders. Medline, Embase, Web of Science, Cochrane Central and PsycINFO were searched for studies on associations between work-related physical or psychosocial risk factors and the occurrence of elbow disorders. Two independent reviewers selected eligible studies and assessed risk of bias (RoB). Results of studies were synthesized narratively. We identified 17 new studies and lateral epicondylitis was the most studied disorder (13 studies). Five studies had a prospective cohort design, eight were cross-sectional and four were case-control. Only one study had no items rated as high RoB. Combined physical exposure indicators (e.g. physical exertion combined with elbow movement) were associated with the occurrence of lateral epicondylitis. No other consistent associations were observed for other physical and psychosocial exposures. These results prevent strong conclusions regarding associations between work-related exposures, and the occurrence of elbow disorders.

Progressive resistance exercise training (PRET) reduces cardiovascular risk factors (CVRF) in the general population. It is unknown if PRET also reduces these risk factors in adults with intellectual disabilities (ID). The aim is to present the protocol of an intervention study that investigates the effect of PRET on CVRF in adults with ID. We will use a repeated time series design with one study group. Adults with mild-to-moderate ID and at least two CVRF are eligible (Netherlands Trial Register, NL8382). During a 12-week baseline period, measurements take place at a 6-week interval. After this, the PRET programme starts for 24 weeks, after which all measurements will be repeated. We will use hierarchical regression models, adjusted for sport activity and medication use, to estimate the effect of PRET. After the intervention, the participants will be followed-up for 12 weeks. We will evaluate factors for successful implementation of exercise in daily life. Primary outcomes are: hypertension, obesity, hypercholesterolemia, diabetes, metabolic syndrome. Secondary outcomes are: physical fitness, sarcopenia, physical activity, activities of daily living, falls, challenging behaviour. If our results show that the PRET programme is effective, it may be a promising non-pharmacological intervention to reduce CVRF in adults with ID.

IntroductionA few cases of serious side effects have been reported of Momordica charantia L. (MC). No comprehensive safety assessment has yet been performed based on human intake.This systematic review aims to evaluate the potential harm of Momordica charantia L. derived products using data from randomized controlled trials.MethodsDatabases Cochrane Library, Pubmed and EMBASE were searched until December 2020. The PRISMA harms checklist was followed. Data extraction was on aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, adverse effects (AE), reasons for drop out related to the intervention and interaction with other treatment. Two authors independently extracted data and bias was evaluated based on the latest version of the Cochrane risk of Bias Tool (RoB 2). Additional safety data were requested from Health Regulatory Agencies, Herbal Medicine Associations and manufacturers.ResultsSeventeen trials met the inclusion criteria. The IRR was calculated for each study ranging from 0.30 (95% CI = 0.12 to 0.75) to 13.00 (95% CI = 0.73 to 230.76) of any adverse events.ConclusionsUnder a daily dosage of 6g of MC-derived products no evidence was seen of harms in humans. In case reports that showed serious harm, MC was used in a liquid form. The safety of traditional MC-based supplements appears more guaranteed when produced under strict quality standards.

Though parechovirus (PeV) and enterovirus (EV) are common causes of central nervous system (CNS) infection in childhood, little is known about their long-term neurologic/neurodevelopmental complications. We investigated, longitudinally over a 5-year period, motor neurodevelopment in term-born newborns and infants with RT-qPCR-confirmed PeV- or EV-CNS infection. Motor neurodevelopment was assessed with standardized tests: Alberta Infant Motor Scale (AIMS), Bayley Scales of Infant and Toddler Development version-3 (Bayley-3-NL), and Movement Assessment Battery for Children version-2 (M-ABC-2-NL) at 6, 12, 24, and 60 months post-infection. Results of children with PeV-CNS infection were compared with those of peers with EV-CNS infection and with Dutch norm references. In the multivariate analyses adjustments were made for age at onset, gender, maternal education, and time from CNS infection Sixty of 172 eligible children aged ≤ 3 months were included. Children with PeV-CNS infection had consistently lower, non-significant mean gross motor function (GMF) Z-scores, compared with peers with EV-CNS infection and population norm-referenced GMF. Their GMF improved between 6 and 24 months and decreased at 5 years. Their fine motor function (FMF) scores fell within the population norm reference. Conclusion: These results suggest that the impact of PeV-A3-CNS infection on gross motor neurodevelopment in young children might manifest later in life. They highlight the importance of longitudinal neurodevelopmental assessments of children with PeV-A3-CNS infection up to school age.What is Known:• Human parechovirus (PeV) is a major cause of central nervous system infection (CNS infection) in newborns and infants.• There is interest in the neurological and neurodevelopmental outcome of newborns and infants with PeV-A3-CNS infection.What is New:• This prospective study compares the motor neurodevelopment of term-born newborns and infants with PeV-A3-CNS infection with those with EV-CNS infection and with norm references.• The results support the importance of follow-up of newborns and infants with PeV-A3-CNS infection to detect subtle neurodevelopmental delay and start early interventions.

Objective To evaluate the effect of exercise programs on reduction of musculoskeletal injury (MSI) risk in military populations. Design Systematic review and meta-analysis. Literature survey A database search was conducted in PubMed/MEDLINE, EMBASE, Cochrane Library, CINAHL, SPORTdiscus, WHO International Clinical Trials Registry Platform Search Portal, Open Gray, National Technical Reports Library, and reference lists of included articles up to July 2019. Randomized and cluster-randomized controlled trials evaluating exercise programs as preventive interventions for MSIs in armed forces compared to other exercise programs or to usual practice were eligible for inclusion. Methodology Two authors independently assessed risk of bias and extracted data. Data were adjusted for clustering if necessary and pooled using the random-effects model when appropriate. Synthesis We included 15 trials in this review, with a total number of 14 370 participants. None of the included trials appeared to be free of any risk of bias. Meta-analysis and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment could be performed for static stretching compared to no stretching (3532 participants), showing low quality of evidence indicating no favorable effect of stretching. Gait retraining, an anterior knee-pain targeted program, and resistance exercises showed cautious favorable effects on reducing injury risk in military personnel. Conclusion The current evidence base for exercise-based MSI prevention strategies in the military is of low quality. Areas worthy of further exploration include the effects of gait retraining, anterior knee-pain targeted programs, agility training, and resistance training programs, on medial tibial stress syndrome incidence, anterior knee pain incidence, attrition due to injuries and any type of MSI, respectively.

IntroductionThe Healthy Ageing and Intellectual Disability (HA-ID) study is a prospective multicentre cohort study in the Netherlands that started in 2008, including 1050 older adults (aged ≥50) with intellectual disabilities (ID). The study is designed to learn more about the health and health risks of this group as they age. Compared with the amount of research in the general population, epidemiological research into the health of older adults with ID is still in its infancy. Longitudinal data about the health of this vulnerable and relatively unhealthy group are needed so that policy and care can be prioritised and for guiding clinical decision making about screening, prevention and treatment to improve healthy ageing.Methods and analysisThis article presents a summary of the previous findings of the HA-ID study and describes the design of the 10-year follow-up in which a wide range of health data will be collected within five research themes: (1) cardiovascular disease; (2) physical activity, fitness and musculoskeletal disorders; (3) psychological problems and psychiatric disorders; (4) nutrition and nutritional state; and (5) frailty.Ethics and disseminationEthical approval for the 10-year follow-up measurements of the HA-ID study has been obtained from the Medical Ethics Review Committee of the Erasmus MC, University Medical Centre Rotterdam (MEC-2019-0562).Trial registration numberThis cohort study is registered in the Dutch Trial Register (NTR number NL8564) and has been conducted according to the principles of the Declaration of Helsinki.

Background: A paucity of studies investigated the association between human parechovirus (HPeV) central nervous system (CNS) infection and motor and neurocognitive development of children. This study describes the gross-motor function (GMF) in young children during 24 months after HPeV-CNS infection compared with children in whom no pathogen was detected. Methods: GMF of children was assessed with Alberta Infant Motor Scale, Bayley Scales of Infant and Toddler Development or Movement Assessment Battery for Children. We conducted multivariate analyses and adjusted for age at onset, maternal education and time from infection. Results: Of 91 included children, at onset

Background: Moderate to severe intrauterine adhesions (IUAs) may greatly impact fertility, predisposing to pregnancy and obstetric complications. The impact of mild IUAs on reproductive performance remains unclear. A systematic review and meta-analysis was performed to examine the long-term reproductive outcomes in women with hysteroscopic identified and treated mild IUAs mild intrauterine adhesions (IUAs) Methods: An electronic literature search was conducted using MEDLINE and EMBASE from inception to June 2019. All prospective cohort, cross-sectional studies or randomized controlled trials Clinical trials in which reproductive outcomes of women with mild IUAs, were reported were included. Results: Five studies, reporting on reproductive outcomes of 229 women with hysteroscopic identified and treated mild IUAs, were included. The pregnancy rate was 62.3% (142 of 228; 95% CI: 0.55–0.72, I 2 25%, p =.21) and in 86.6% (123 of 142) a live birth was encountered (95% CI: 0.71–0.97) with 83.1% (108 out of 130) term deliveries (95% CI: 0.53–0.95). A miscarriage was reported in 10% (13 of 130; 95% CI: 0.02–0.26). Due to the lack of a control group, reproductive outcomes were compared to a general population. Pregnancy and live birth rates were significantly lower in women with identified and treated mild IUAs, 90% versus 62.3% and respectively 99.5% versus 86.6%. The miscarriage rate was similar. Data on obstetric and neonatal outcomes are lacking. Conclusions: Women with hysteroscopic identified and treated mild IUAs seem to have lower pregnancy and live birth rate compared to the general population. Future studies consisting of a large cohort of women with hysteroscopic identified and treated IUAs with structural follow-up and a control group are needed to confirm our findings.

ObjectiveTo determine the most effective interventions in recently detoxified, alcohol dependent patients for implementation in primary care.DesignSystematic review and network meta-analysis.Data sourcesMedline, Embase, PsycINFO, Cochrane CENTRAL, ClinicalTrials.gov, and the World Health Organization’s International Clinical Trials Registry Platform.Study selectionRandomised controlled trials comparing two or more interventions that could be used in primary care. The population was patients with alcohol dependency diagnosed by standardised clinical tools and who became detoxified within four weeks.Data extractionOutcomes of interest were continuous abstinence from alcohol (effectiveness) and all cause dropouts (as a proxy for acceptability) at least 12 weeks after start of intervention.Results64 trials (43 interventions) were included. The median probability of abstinence across placebo arms was 25%. Compared with placebo, the only intervention associated with increased probability of abstinence and moderate certainty evidence was acamprosate (odds ratio 1.86, 95% confidence interval 1.49 to 2.33, corresponding to an absolute probability of 38%). Of the 62 included trials that reported all cause dropouts, interventions associated with a reduced number of dropouts compared with placebo (probability 50%) and moderate certainty of evidence were acamprosate (0.73, 0.62 to 0.86; 42%), naltrexone (0.70, 0.50 to 0.98; 41%), and acamprosate-naltrexone (0.30, 0.13 to 0.67; 17%). Acamprosate was the only intervention associated with moderate confidence in the evidence of effectiveness and acceptability up to 12 months. It is uncertain whether other interventions can help maintain abstinence and reduce dropouts because of low confidence in the evidence.ConclusionsEvidence is lacking for benefit from interventions that could be implemented in primary care settings for alcohol abstinence, other than for acamprosate. More evidence from high quality randomised controlled trials is needed, as are strategies using combined interventions (combinations of drug interventions or drug and psychosocial interventions) to improve treatment of alcohol dependency in primary care.Systematic review registrationPROSPERO CRD42016049779.

Background: Human parechoviruses are a major cause of CNS infection in neonates and young children. They have been implicated in neurological sequelae and neurodevelopmental delay. However, the magnitude of this effect has not been systematically reviewed or assessed with meta-analyses. We investigated short-term, medium-term, and long-term neurological sequelae and neurodevelopmental delay in neonates and young children after parechovirus-CNS-infection. Methods: In this systematic review and meta-analyses of studies, we searched PubMed, Embase, and PsycInfo, from the inception of the database until March 18, 2019, for reviews, systematic reviews, cohort studies, case series, and case control studies reporting on neurological or neurodevelopmental outcomes of children 3 months or younger with parechovirus infection of the CNS. Studies that were published after Dec 31, 2007, assessed children younger than 16 years, detailed parechoviruses infection of the CNS (confirmed by PCR), and followed up on neurological and neurodevelopmental outcomes were included. Studies published before Dec 31, 2007, were excluded. The predefined primary outcomes were the proportions of children with neurological sequelae, impairment in auditory or visual functions, or gross motor function delay. The proportion of children in whom neurological or neurodevelopmental outcomes were reported was pooled in meta-analyses. For each outcome variable we calculated the pooled proportion with 95% CI. The proportion of children in whom neurological or neurodevelopmental outcomes were reported was extracted by one author and checked by another. Two authors independently assessed the methodological quality of the studies. Findings: 20 studies were eligible for quantitative synthesis. The meta-analyses showed an increasing proportion of children with neurological sequelae over time: 5% during short-term follow-up (pooled proportion 0·05 [95% CI 0·03–0·08], I2=0·00%; p=0·83) increasing to 27% during long-term follow-up (0·27 [0·17–0·40], I2=52·74%; p=0·026). The proportion of children with suspected neurodevelopmental delay was 9% or more during long-term follow-up. High heterogeneity and methodological issues in the included studies mean that the results should be interpreted with caution. Interpretation: This systematic review suggests the importance of long follow-up, preferably up to preschool or school age (5–6 years), of children with parechovirus infection of the CNS. Although not clinically severe, we found an increasing proportion of neonates and young children with CNS infection had associated neurological sequelae and neurodevelopmental delay over time. We recommend the use of standardised methods to assess neurological and neurodevelopmental functions of these children and to compare results with age-matched reference groups. Funding: No funding was received for this study.

Systematic reviews are a valuable tool to inform healthcare decision-making.1 2 While a single randomised controlled trial (RCT) is insufficient to definitively guide healthcare decisions, a systematic review synthesising multiple RCTs can overcome this limitation. The results of rigorous systematic reviews possess wide-ranging applicability to numerous stakeholders within the evidence-based medicine ‘ecosystem’. Clinicians consult systematic reviews to inform their clinical decisions.3 Researchers rely on systematic reviews to identify knowledge gaps in existing literature.4 Health policymakers use systematic review evidence to inform practice guidelines and legislation.5 6 Journal editors often prioritise systematic reviews for their impact on readership attention and journal metrics.7 Finally, patients are empowered by systematic reviews that assess the beneficial and harmful patient-important outcomes of available management strategies.8 Evidently, systematic review authors have an important responsibility to ensure their findings provide the most accurate results possible. The biomedical literature expands by 22 systematic reviews daily,9 with no evidence that production is waning. More systematic reviews are desirable if they identify and inform important research questions that improve patient care.10 However, production of this magnitude is problematic when systematic reviews offer ‘extensive redundancy, little value, misleading claims and/or vested interests’.11 As we outlined in part 1, bias is a systematic deviation from the truth in the results of a research study due to limitations in study design, conduct, or analysis.2 Deviations may either overestimate or underestimate a study’s true findings depending of the type and magnitude of bias. As the results of a systematic review are only as valid as the studies it includes, pooling biased results from different studies can compromise the credibility of systematic review findings when no assessment, or a poor assessment, of risk of bias is performed.3 12 Inadequate study design, conduct, or analysis …

Systematic reviews fulfil a vital role in modern medicine.1 However, the results of systematic reviews are only as valid as the studies they include.2 Pooling flawed, or biased, results from different studies can compromise the credibility of systematic review findings. Bias is a systematic deviation from the truth in the results of a research study that can manifest due to limitations in study design, conduct, or analysis.3 The results of sport and exercise medicine research, like results in other fields, are vulnerable to bias.4 It is important that systematic review authors assess for bias in a way that enables a judgement about whether a review outcome is at risk of bias due to methodological limitations in included studies. This two-part education primer focuses on how systematic review authors can perform and interpret risk of bias assessments to avoid misleading systematic review conclusions. In this editorial, we introduce the concept of risk of bias, and the principles of assessing risk of bias. Different biases have effects that vary in direction and magnitude.3 5 It is challenging to precisely determine how bias may overestimate or underestimate a study’s true findings. In fact, bias does not always result in distorted study findings and one can never be certain that bias is present when a study has methodological limitations. However, methodological limitations in study design, conduct, or analysis can be consistently associated with inflated research findings.5 Due to this uncertainty, study outcomes are considered to be at risk of bias rather than ‘biased’. Studies with ‘some concerns’ or at ‘high’ risk of bias in design, conduct, analysis, or reporting are at greater risk of inflated findings compared with studies at ‘low’ risk of bias, negatively …

Assessment of risk of bias is regarded as an essential component of a systematic review on the effects of an intervention. The most commonly used tool for randomised trials is the Cochrane risk-of-bias tool. We updated the tool to respond to developments in understanding how bias arises in randomised trials, and to address user feedback on and limitations of the original tool.

Summary Flaws in the conduct of randomized trials can lead to biased estimation of the intervention effect. Methods for adjustment of within-trial biases in meta-analysis include the use of empirical evidence from an external collection of meta-analyses, and the use of expert opinion informed by the assessment of detailed trial information. Our aim is to present methods to combine these two approaches to gain the advantages of both. We make use of the risk of bias information that is routinely available in Cochrane reviews, by obtaining empirical distributions for the bias associated with particular bias profiles (combinations of risk of bias judgements). We propose three methods: a formal combination of empirical evidence and opinion in a Bayesian analysis; asking experts to give an opinion on bias informed by both summary trial information and a bias distribution from the empirical evidence, either numerically or by selecting areas of the empirical distribution. The methods are demonstrated through application to two example binary outcome meta-analyses. Bias distributions based on opinion informed by trial information alone were most dispersed on average, and those based on opinions obtained by selecting areas of the empirical distribution were narrowest. Although the three methods for combining empirical evidence with opinion vary in ease and speed of implementation, they yielded similar results in the two examples.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: This review aims to look at the benefits and harms of pre‐emptive kidney transplantation compared with kidney transplantation after dialysis for patients with end-stage kidney disease.

Objective: To investigate the longitudinal association between the impact of fatigue and health-related quality of life and to determine if potential confounders distorted this association. Design: Baseline, 3-, 6- and 12-week assessments of a randomized clinical trial were used. Setting: Outpatient rehabilitation centre. Subjects: Patients with idiopathic Parkinson’s disease. Methods: Quality of life was assessed with the Parkinson’s Disease Questionnaire-39 and the Multidimensional Fatigue Inventory was used to assess fatigue. Time-independent and time-dependent factors were investigated for their bivariate association with quality of life by applying random coefficient analysis. Candidate confounders were successively added to the longitudinal association model to determine if the relationship between quality of life and fatigue was distorted. A change beyond 15% of found regression coefficient of the Multidimensional Fatigue Inventory was considered significant. Results: One hundred and fifty-three patients were included. Impact of fatigue was significantly associated with poorer quality of life (β = 0.24, 95% confidence interval = 0.18 to 0.30). This association was significantly distorted by depression (30.0%) and anxiety (24.1%). No distortion was found for other factors. After controlling for confounders, fatigue remained significantly associated with quality of life (β = 0.12, 95% confidence interval = 0.06 to 0.18, r2 = 2.3%). Conclusions: Our results suggest that patients who experience fatigue tend to report lower levels of quality of life. However, this longitudinal relationship is confounded by depression and anxiety and suggests that the unique contribution of fatigue to overall quality of life is rather small.

Purpose To critically appraise, compare and summarize the measurement properties of self-report fatigue questionnaires validated in patients with multiple sclerosis (MS), Parkinson’s disease (PD) or stroke. Methods MEDLINE, EMBASE, PsycINFO, CINAHL and SPORTdiscus were searched. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to assess the methodological quality of studies. A qualitative data synthesis was performed to rate the measurement properties for each questionnaire. Results Thirty-eight studies out of 5,336 records met the inclusion criteria, evaluating 31 questionnaires. Moderate evidence was found for adequate internal consistency and structural validity of the Fatigue Scale for Motor and Cognitive functions (FSMC) and for adequate reliability and structural validity of the Unidimensional Fatigue Impact Scale (U-FIS) in MS. Conclusions We recommend the FSMC and U-FIS in MS. The Functional Assessment of Chronic Illness Therapy Fatigue subscale (FACIT-F) and Fatigue Severity Scale (FSS) show promise in PD, and the Profile of Mood States Fatigue subscale (POMS-F) for stroke. Future studies should focus on measurement error, responsiveness and interpretability. Studies should also put emphasis on providing input for the theoretical construct of fatigue, allowing the development of questionnaires that reflect generic and disease-specific symptoms of fatigue. Electronic supplementary material The online version of this article (doi:10.1007/s11136-011-0009-2) contains supplementary material, which is available to authorized users.

To investigate the longitudinal association between fatigue and physical activity in Parkinson's disease (PD) and determine whether this association is distorted by potential confounders. Data from baseline, 3, 6, and 12 week assessments in a single blind randomized clinical trial with crossover design were used (N = 153). The Multidimensional Fatigue Inventory (MFI) was used to assess fatigue and an activity monitor to measure amount of physical activity (defined as % dynamic activity during each monitoring session). Time-independent and time-dependent factors were investigated for their possible univariate association with dynamic activity. Random coefficient analysis was applied. Candidate confounders were successively added to the longitudinal association model to determine if the association between dynamic activity and fatigue was distorted. A proportional change beyond 15% was considered to be significant. Fatigue was significantly associated with physical activity (β = 20.099, SE = 0.032, P = 0.002). This association was not significantly distorted by type of intervention, age, gender, social support, disease duration, disease severity, motor impairment, cognition, anxiety, or medication intake. Depression caused proportional change of 22.2% in the regression coefficient of MFI. After controlling for depression, a significant association between MFI and dynamic activity remained (β = 20.121, SE = 0.036, P = 0.000). The association found between fatigue and dynamic activity suggests that patients who experience higher levels of fatigue are less physically active. However, the total explained variance of dynamic activity by fatigue alone was small, suggesting that fatigue is only a minor factor in the complex of behavioral aspects that affect the amount of physical activity in patients with PD. © 2009 Movement Disorder Society.

Background Factors contributing to subjective fatigue in people with idiopathic Parkinson’s disease (PD) are not well known. This makes it difficult to manage fatigue effectively in PD. Objectives To evaluate the effects of pharmacological and non-pharmacological interventions, compared to an inactive control intervention, on subjective fatigue in people with PD. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); MEDLINE (via PubMed); Ovid EMBASE; EBSCO CINAHL; Ovid PsycINFO; PEDro; and the WHO International Clinical Trials Registry Platform Search Portal up to April 2015. References of included studies and identified review articles were screened for additional studies. There were no restrictions based on language, date of publication or study setting. Selection criteria Randomised controlled trials (RCTs) that report on subjective fatigue in people with PD. Data collection and analysis Two review authors independently performed study selection, data collection and risk of bias assessments. Main results Eleven studies were eligible for this systematic review, with a total of 1817 people. Three studies included only people who experienced clinically relevant fatigue (Fatigue Severity Scale score ≥ 4 out of 7 or Multidimensional Fatigue Inventory total score > 48 out of 100), whereas all other studies did not select participants on the basis of experienced fatigue. Nine studies investigated the effects of medication (i.e. levodopa-carbidopa, memantine, rasagiline, caffeine, methylphenidate, modafinil or doxepin) on subjective fatigue. All studies were placebo controlled. There was insufficient evidence to determine the effect of doxepin on the impact of fatigue on activities in daily life (ADL) or fatigue severity (one study, N = 12, standardised mean difference (SMD) = -1.50, 95% confidence interval (CI) -2.84 to -0.15; low quality evidence). We found high quality evidence that rasagiline reduced or slowed down the progression of physical aspects of fatigue (one study, N = 1176, SMD = -0.27, 95% CI -0.39 to -0.16, I2 = 0%). None of the other pharmacological interventions affected subjective fatigue in PD. With regard to adverse effects, only levodopa-carbidopa showed an increase for the risk of nausea (one study, N = 361, risk ratio (RR) = 1.85, 95% CI 1.05 to 3.27; high quality evidence). Two studies investigated the effect of exercise on fatigue compared with usual care. We found low quality evidence for the effect of exercise on reducing the impact of fatigue on ADL or fatigue severity (two studies, N = 57, SMD = -0.45, 95% CI -1.21 to 0.32, I2 = 44%). Authors' conclusions Based on the current evidence, no clear recommendations for the treatment of subjective fatigue in PD can be provided. Doxepin may reduce the impact of fatigue on ADL and fatigue severity; however, this finding has to be confirmed in high quality studies. Rasagiline may be effective in reducing levels of physical fatigue in PD. No evidence was found for the effectiveness of levodopa-carbidopa, memantine, caffeine, methylphenidate, modafinil or exercise. Studies are needed to investigate the effect of exercise intensity on exercise capacity and subjective fatigue. Future studies should focus on interventions that address the maladaptive behavioural or cognitive aspects of fatigue in people with PD. Characteristics, such as severity and nature of perceived fatigue and underlying mood disorders should be considered to identify responders and non-responders when studying interventions for fatigue. The development of a core-set of self-report fatigue questionnaires with established responsiveness and known minimal important difference values will facilitate the interpretation of change in fatigue scores.

The purpose of the study is to (1) estimate the direction, clinical relevance, and duration of health-related quality-of-life (HRQL) change in the first year following esophageal cancer surgery and (2) to assess the robustness of the estimates by subgroup and sensitivity analyses, and an exploration of publication bias. A systematic literature search in MEDLINE, EMBASE, CINAHL, PsychINFO, and CENTRAL to identify randomized and non-randomized studies was performed. We compared the baseline HRQL data with 3-, 6-, 9-, or 12-month follow-ups to estimate the magnitude and duration of HRQL change. These estimates were then classified as trivial, small, medium, or large. Primary outcomes were role functioning, eating, and fatigue. Secondary outcomes were physical and social functioning, dysphagia, pain, and coughing problems. We conducted subgroup analysis for open surgery, open surgery preceded by neoadjuvant therapy, and minimally invasive surgery. Sensitivity analyses assessed the influence of study design, transformation/imputation of the data, and HRQL questionnaire used. We included the data from 15 studies to estimate the change in 28 HRQL outcomes after esophageal cancer surgery. The main analysis showed that patients' social functioning deteriorated. Symptoms of fatigue, pain, and coughing problems increased. These changes lasted for 9-12 months, although some symptoms persisted beyond the first year after surgery. For many other HRQL outcomes, estimates were only robust after subgroup or sensitivity analyses (e.g., role and physical functioning), or remained too heterogeneous to interpret (e.g., eating and dysphagia). Patients will experience a clinically relevant and long-lasting deterioration in HRQL after esophageal cancer surgery. However, for many HRQL outcomes, more and better quality evidence is needed.

Background Asthma is the most common chronic disease in childhood and prevalence is also high in adulthood, thereby placing a considerable burden on healthcare resources. Therefore, effective asthma management is important to reduce morbidity and to optimise utilisation of healthcare facilities. Objectives To review the effectiveness of nurse-led asthma care provided by a specialised asthma nurse, a nurse practitioner, a physician assistant or an otherwise specifically trained nursing professional, working relatively independently from a physician, compared to traditional care provided by a physician. Our scope included all outpatient care for asthma, both in primary care and in hospital settings. Search methods We carried out a comprehensive search of databases including The Cochrane Library, MEDLINE and EMBASE to identify trials up to August 2012. Bibliographies of relevant papers were searched, and handsearching of relevant publications was undertaken to identify additional trials. Selection criteria Randomised controlled trials comparing nurse-led care versus physician-led care in asthma for the same aspect of asthma care. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Main results Five studies on 588 adults and children were included concerning nurse-led care versus physician-led care. One study included 154 patients with uncontrolled asthma, while the other four studies including 434 patients with controlled or partly controlled asthma. The studies were of good methodological quality (although it is not possible to blind people giving or receiving the intervention to which group they are in). There was no statistically significant difference in the number of asthma exacerbations and asthma severity after treatment (duration of follow-up from six months to two years). Only one study had healthcare costs as an outcome parameter, no statistical differences were found. Although not a primary outcome, quality of life is a patient-important outcome and in the three trials on 380 subjects that reported on this outcome, there was no statistically significant difference (standardised mean difference (SMD) -0.03; 95% confidence interval (CI) -0.23 to 0.17). Authors' conclusions We found no significant difference between nurse-led care for patients with asthma compared to physician-led care for the outcomes assessed. Based on the relatively small number of studies in this review, nurse-led care may be appropriate in patients with well-controlled asthma. More studies in varied settings and among people with varying levels of asthma control are needed with data on adverse events and health-care costs.

Objective: To investigate the predictive value of gait speed for community walking in Parkinson's disease and to develop a multivariate prediction model for community walking. Design: Data from baseline assessments in a randomized clinical trial were used. Subjects: A total of 153 patients with Parkinson's disease were included. Methods: Community walking was evaluated using the mobility domain of the Nottingham Extended Activities of Daily Living Index (NEAI). Patients who scored 3 points on item 1 ("Did you walk around outside?") and item 5 ("Did you cross roads?") were considered community walkers. Gait speed was measured with the 6-m or 10-m timed walking test. Age, gender, marital status, disease duration, disease severity, motor impairment, balance, freezing of gait, fear of falling, previous falls, cognitive function, executive function, fatigue, anxiety and depression were investigated for their contribution to the multivariate model. Results: Seventy patients (46%) were classified as community walkers. A gait speed of 0.88 m/s correctly predicted 70% of patients as community walkers. The multivariate model, including gait speed and fear of falling, correctly predicted 78% of patients as community walkers. Conclusion: Timed walking tests are valid measurements to predict community walking in Parkinson's disease. However, evaluation of community walking should include an assessment of fear of falling. © 2013 The Authors.

BACKGROUND: Factors contributing to subjective fatigue in people with idiopathic Parkinson’s disease (PD) are not well known. This makes it difficult to manage fatigue effectively in PD. OBJECTIVES: To evaluate the effects of pharmacological and non‐pharmacological interventions, compared to an inactive control intervention, on subjective fatigue in people with PD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); MEDLINE (via PubMed); Ovid EMBASE; EBSCO CINAHL; Ovid PsycINFO; PEDro; and the WHO International Clinical Trials Registry Platform Search Portal up to April 2015. References of included studies and identified review articles were screened for additional studies. There were no restrictions based on language, date of publication or study setting. SELECTION CRITERIA: Randomised controlled trials (RCTs) that report on subjective fatigue in people with PD. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data collection and risk of bias assessments. MAIN RESULTS: Eleven studies were eligible for this systematic review, with a total of 1817 people. Three studies included only people who experienced clinically relevant fatigue (Fatigue Severity Scale score ≥ 4 out of 7 or Multidimensional Fatigue Inventory total score > 48 out of 100), whereas all other studies did not select participants on the basis of experienced fatigue. Nine studies investigated the effects of medication (i.e. levodopa‐carbidopa, memantine, rasagiline, caffeine, methylphenidate, modafinil or doxepin) on subjective fatigue. All studies were placebo controlled. There was insufficient evidence to determine the effect of doxepin on the impact of fatigue on activities in daily life (ADL) or fatigue severity (one study, N = 12, standardised mean difference (SMD) = ‐1.50, 95% confidence interval (CI) ‐2.84 to ‐0.15; low quality evidence). We found high quality evidence that rasagiline reduced or slowed down the progression of physical aspects of fatigue (one study, N = 1176, SMD = ‐0.27, 95% CI ‐0.39 to ‐0.16, I(2) = 0%). None of the other pharmacological interventions affected subjective fatigue in PD. With regard to adverse effects, only levodopa‐carbidopa showed an increase for the risk of nausea (one study, N = 361, risk ratio (RR) = 1.85, 95% CI 1.05 to 3.27; high quality evidence). Two studies investigated the effect of exercise on fatigue compared with usual care. We found low quality evidence for the effect of exercise on reducing the impact of fatigue on ADL or fatigue severity (two studies, N = 57, SMD = ‐0.45, 95% CI ‐1.21 to 0.32, I(2) = 44%). AUTHORS' CONCLUSIONS: Based on the current evidence, no clear recommendations for the treatment of subjective fatigue in PD can be provided. Doxepin may reduce the impact of fatigue on ADL and fatigue severity; however, this finding has to be confirmed in high quality studies. Rasagiline may be effective in reducing levels of physical fatigue in PD. No evidence was found for the effectiveness of levodopa‐carbidopa, memantine, caffeine, methylphenidate, modafinil or exercise. Studies are needed to investigate the effect of exercise intensity on exercise capacity and subjective fatigue. Future studies should focus on interventions that address the maladaptive behavioural or cognitive aspects of fatigue in people with PD. Characteristics, such as severity and nature of perceived fatigue and underlying mood disorders should be considered to identify responders and non‐responders when studying interventions for fatigue. The development of a core‐set of self‐report fatigue questionnaires with established responsiveness and known minimal important difference values will facilitate the interpretation of change in fatigue scores.

Introduction The Multidimensional Fatigue Inventory (MFI) is commonly used in patients with Parkinson's disease (PD). However, most measurement properties have not been investigated in this population. The aim of this study was to investigate internal consistency, test-retest reliability, measurement error, structural validity, and floor and ceiling effects of the MFI in PD. Methods Patients with PD ( N = 153) completed the MFI at baseline and week 3 in a randomized clinical trial. Cronbach's α, intraclass correlation coefficient (ICC), and the smallest detectable change (SDC) were calculated. Bland and Altman analysis was performed. Principal Component Analysis (PCA) was used to explore structural validity. Floor and ceiling effects were investigated. Results Cronbach's α for the MFI-total and subscales ranged from 0.74 (reduced motivation (RM)) to 0.92 (MFI-total). ICC's ranged from 0.65 (mental fatigue (MF) to 0.81 (physical fatigue (PF)), SDC ranged from 4 points (PF and RM) to 15 points (MFI-total). Bland and Altman analysis showed no systematic differences between assessments. A floor effect was found for MF and ceiling effects for PF and reduced activity (RA). A four-factor model was extracted, combining general fatigue (GF) and PF as one factor. Conclusions The MFI is reliable and valid to assess fatigue in patients with PD. Clinicians and researchers interested in assessing specific aspects of fatigue should consider interpreting GF and PF as one subscale measuring physical aspects of fatigue. To establish whether the MFI can detect meaningful changes, studies on anchor-based responsiveness and the minimal important change are needed in PD.