Physical and psychosocial work-related exposures and the occurrence of disorders of the shoulder: A systematic review update.

This review is an update of a previous systematic review and assesses the evidence for the association of work-related physical and psychosocial risk factors and specific disorders of the shoulders. Medline, Embase, Web of Science Core Collection, Cochrane Central and PsycINFO were searched and study eligibility and risk of bias assessment was performed by two independent reviewers. A total of 14 new articles were added with the majority focusing on rotator cuff syndrome (RCS) with seven studies. Nine articles reported psychosocial exposures in addition to physical exposures. The strongest evidence was found for the association between elevation, repetition, force and vibration and the occurrence of SIS and tendinosis/tendonitis. Evidence also suggests that psychosocial exposures are associated with the occurrence of RCS and tendinosis/tendonitis. Other findings were inconsistent which prevents drawing strong conclusions.

Prevalence of swallowing difficulties and associated factors in older people with intellectual disabilities.

BACKGROUND: We investigated the prevalence of swallowing difficulties and associated factors in people with intellectual disability. METHODS: We included people aged 50+ receiving care for people with intellectual disabilities. The Dysphagia Disorder Survey (DDS) was used to assess swallowing difficulties. We determined the agreement between the DDS and swallowing difficulties in medical records. We used logistic regression analyses to explore associated factors. RESULTS: One thousand and fifty people were included. The prevalence of swallowing difficulties was 43.8%. Swallowing difficulties were not reported in the medical records of 83.3% of these cases. Frailty (odds ratio (OR) = 4.22, 95% CI = 2.05-8.71), mobility impairment (OR = 2.50, 95% CI = 1.01-6.19), and mealtime dependency (OR = 3.05, 95% CI = 1.10-8.47) were independently associated with swallowing difficulties. CONCLUSION: Swallowing difficulties are prevalent in older people with intellectual disability but may be under-recognised. Frailty may be a good indicator for population-based screening for swallowing difficulties.

Designing tailored maintenance strategies for systematic reviews and clinical practice guidelines using the Portfolio Maintenance by Test-Treatment (POMBYTT) framework.

BACKGROUND: Organizations face diverse contexts and requirements when updating and maintaining their portfolio, or pool, of systematic reviews or clinical practice guidelines they need to manage. We aimed to develop a comprehensive, theoretical framework that might enable the design and tailoring of maintenance strategies for portfolios containing systematic reviews and guidelines. METHODS: We employed a conceptual approach combined with a literature review. Components of the diagnostic test-treatment pathway used in clinical healthcare were transferred to develop a framework specifically for systematic review and guideline portfolio maintenance strategies. RESULTS: We developed the Portfolio Maintenance by Test-Treatment (POMBYTT) framework comprising diagnosis, staging, management, and monitoring components. To illustrate the framework's components and their elements, we provided examples from both a clinical healthcare test-treatment pathway and a clinical practice guideline maintenance scenario. Additionally, our literature review provided possible examples for the elements in the framework, such as detection variables, detection tests, and detection thresholds. We furthermore provide three example strategies using the framework, of which one was based on living recommendations strategies. CONCLUSIONS: The developed framework might support the design of maintenance strategies that could contain multiple options besides updating to manage a portfolio (e.g. withdrawing and archiving), even in the absence of the target condition. By making different choices for variables, tests, test protocols, indications, management options, and monitoring, organizations might tailor their maintenance strategy to suit specific contexts and needs. The framework's elements could potentially aid in the design by being explicit about the operational aspects of maintenance strategies. This might also be helpful for end-users and other stakeholders of systematic reviews and clinical practice guidelines.

Physical and psychosocial work-related exposures and the incidence of carpal tunnel syndrome: A systematic review of prospective studies.

This systematic review summarizes the evidence on associations between physical and psychosocial work-related exposures and the development of carpal tunnel syndrome (CTS). Relevant databases were searched up to January 2020 for cohort studies reporting associations between work-related physical or psychosocial risk factors and the incidence of CTS. Two independent reviewers selected eligible studies, extracted relevant data, and assessed risk of bias (RoB). We identified fourteen articles for inclusion which reported data from nine cohort studies. Eight reported associations between physical exposure and the incidence of CTS and five reported associations between psychosocial exposures and the incidence of CTS. Quality items were generally rated as unclear or low RoB. Work-related physical exposure factors including high levels of repetition, velocity, and a combination of multiple physical exposures were associated with an increased risk of developing CTS. No other consistent associations were observed for physical or psychosocial exposures at work and CTS incidence.

Exposure to hand-arm vibrations in the workplace and the occurrence of hand-arm vibration syndrome, Dupuytren's contracture, and hypothenar hammer syndrome: a systematic review and meta-analysis.

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.

Physical and psychosocial work-related exposures and the occurrence of disorders of the elbow: A 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.

The Effect of Progressive Resistance Exercise Training on Cardiovascular Risk Factors in People with Intellectual Disabilities: A Study Protocol.

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.

Healthy Ageing and Intellectual Disability study: summary of findings and the protocol for the 10-year follow-up study.

INTRODUCTION: The 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 ANALYSIS: This 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 DISSEMINATION: Ethical 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 NUMBER: This 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.

Neurodevelopmental outcomes of newborns and infants with parechovirus and enterovirus central nervous infection: a 5-year longitudinal study.

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.

Reproductive outcomes in women with mild intrauterine adhesions; a systematic review and meta-analysis.

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, I2 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.

Treatment interventions to maintain abstinence from alcohol in primary care: systematic review and network meta-analysis.

OBJECTIVE: To determine the most effective interventions in recently detoxified, alcohol dependent patients for implementation in primary care. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Medline, Embase, PsycINFO, Cochrane CENTRAL, ClinicalTrials.gov, and the World Health Organization's International Clinical Trials Registry Platform. STUDY SELECTION: Randomised 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 EXTRACTION: Outcomes 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. RESULTS: 64 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. CONCLUSIONS: Evidence 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 REGISTRATION: PROSPERO CRD42016049779.

Neurological and neurodevelopmental outcomes after human parechovirus CNS infection in neonates and young children: a systematic review and meta-analysis.

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.

Exercise Programs to Reduce the Risk of Musculoskeletal Injuries in Military Personnel: A Systematic Review and Meta-Analysis.

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.

Outcome measurement instruments for peripheral vascular malformations and an assessment of the measurement properties: a systematic review.

PURPOSE: The Outcome measures for vascular malformation (OVAMA) group reached consensus on the core outcome domains for the core outcome set (COS) for peripheral vascular malformations (venous, lymphatic and arteriovenous malformations). However, it is unclear which instruments should be used to measure these domains. Therefore, our aims were to identify all outcome measurement instruments available for vascular malformations, and to evaluate their measurement properties. METHODS: With the first literature search, we identified outcomes and instruments previously used in prospective studies on vascular malformations. A second search yielded studies on measurement properties of patient- and physician-reported instruments that were either developed for vascular malformations, or used in prospective studies. If the latter instruments were not specifically validated for vascular malformations, we performed a third search for studies on measurement properties in clinically similar diseases (vascular or lymphatic diseases and benign tumors). We assessed the methodological quality of these studies following the Consensus-based Standards for the selection of health Measurement Instruments methodology, and evaluated the quality of the measurement properties. RESULTS: The first search yielded 27 studies, none using disease-specific instruments. The second and third search included 22 development and/or validation studies, concerning six instruments. Only the Lymphatic Malformation Function Instrument was developed specifically for vascular malformations. Other instruments were generic QoL instruments developed and/or partly validated for clinically similar diseases. CONCLUSIONS: Additional research on measurement properties is needed to assess which instruments may be included in the COS. This review informs the instrument selection and/or the development of new instruments. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, 42017056242.

Longitudinal Association Between Human Parechovirus Central Nervous System Infection and Gross-Motor Neurodevelopment in Young Children.

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 <24 months of age, 11 had HPeV-CNS infection and in 47 no pathogen was detected. Nineteen children were excluded because of the presence of other infection, preterm birth or genetic disorder, and in 14 children, parents refused to consent for participation. We found no longitudinal association between HPeV-CNS infection and GMF (ß = -0.53; 95% confidence interval: -1.18 to 0.07; P = 0.11). At 6 months, children with HPeV-CNS infection had suspect GMF delay compared with the nonpathogen group (mean difference = 1.12; 95% confidence interval: -1.96 to -0.30; P = 0.03). This difference disappeared during 24-month follow-up and, after adjustment for age at onset, both groups scored within the normal range for age. Maternal education and time from infection did not have any meaningful influence. CONCLUSIONS: We found no longitudinal association between HPeV-CNS infection and GMF during the first 24-month follow-up. Children with HPeV-CNS infection showed a suspect GMF delay at 6-month follow-up. This normalized during 24-month follow-up.

Therapeutic interventions for alcohol dependence in non-inpatient settings: a systematic review and network meta-analysis (protocol).

BACKGROUND: Alcohol dependence is common and serious cause of social and physical harm. However, the optimal management of those with moderate and severe alcohol dependence in primary and community care after detoxification remains unclear. The aim of this review is to evaluate the effectiveness of interventions for maintaining abstinence in people with alcohol dependence following detoxification. METHODS: We will systematically search electronic databases and clinical trial registries for randomized controlled trials (RCTs) examining the effectiveness of pharmacological and/or psychosocial interventions for maintaining abstinence in recently detoxified, alcohol-dependent adults. The searches will be complemented by checking references and citations from included studies and other relevant systematic reviews. No limitation on language, year, or publication status will be applied. RCTs will be selected using prespecified criteria. Descriptive information, study characteristics, and results of eligible RCTs will be extracted. A revised version of the Cochrane Risk of Bias tool (RoB 2.0) will be used to assess the risk of bias in eligible RCTs. Results will be synthesized and analyzed using network meta-analysis (NMA). Overall strength of the evidence and publication bias will be evaluated. Subgroup and sensitivity analysis will also be performed. DISCUSSION: This network meta-analysis aims to appraise and summarize the total evidence of therapeutic interventions for alcohol-dependent patients that require support for detoxification and can be treated in the community. The evidence will determine which combination of interventions are most promising for current practice and further investigation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016049779.

Treatment of Fatigue in Parkinson Disease.

CLINICAL QUESTION: Which pharmacological and nonpharmacological interventions are associated with improvement in general, physical, or mental fatigue and minimal adverse effects in patients with Parkinson disease (PD)? BOTTOM LINE: Rasagiline, modafinil, and doxepin are associated with improvement in fatigue and are not associated with increased risk of adverse effects in patients with PD. However, the quality of evidence is limited and does not provide a clear basis for treatment decisions.

Interventions for fatigue in Parkinson's disease.

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.