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PubMed2006

Quality assessment of observational studies is not commonplace in systematic reviews.

BACKGROUND AND OBJECTIVE: To review current practice in the assessment of the quality of original observational studies included in systematic reviews. MATERIALS AND METHODS: Examination of all systematic reviews identified by a basic PubMed search for the years 1999-2000 (32 reviews) and 2003-2004 (98 reviews). English language systematic reviews published in peer-reviewed journals was the setting. Each review was evaluated for the use of quality assessment of original observational studies and if quality assessment occurred, what type of assessment was used. RESULTS: Quality assessment occurred in 22% of systematic reviews identified in 1999-2000 compared with 50% of reviews identified from 2003-2004. All earlier reviews devised their own quality assessment criteria, whereas in 2003-2004 10 different quality assessment techniques were identified. CONCLUSIONS: Quality assessment does not routinely occur in systematic reviews of observational studies. Where it does occur, there is no clear consensus in the method used.

Humans↗

PubMed2003

Clinical evidence for enteral nutritional support with glutamine: a systematic review.

OBJECTIVE: The purpose of this systematic review was to locate and assess the quality of scientific evidence to establish a graded recommendation based on the effectiveness of glutamine-enriched enteral nutrition in different medical and surgical conditions. We were concerned with the following topics: 1) benefits of enteral administration of glutamine in different pathologic conditions, and 2) dose, duration, and time of initiation of glutamine-enriched diets. METHODS: The sources consulted for the search were MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Healthstar and HSTAT. Ninety-one studies were assessed; after a methodologic review (primary review), only 16 studies met the inclusion criteria for analysis by a group of experts (secondary review). The coordinators supervised all data, and a final consensus was reached among the coordinators, experts, and methodologists. RESULTS AND CONCLUSIONS: Glutamine-enriched diets showed good overall tolerance, improvement of immunologic aspects in multiple trauma patients, cost reduction in critically ill patients, and improvement of mucositis in post-chemotherapy patients (grade B recommendations). The doses given and the duration of therapy varied widely depending on the pathologic condition. Intake of 20 to 30 g/d, early initiation of diet, and maintenance for 5 d or longer are recommended (grade C recommendations).

Critical Illness↗

PubMed2000

Autogenic training for stress and anxiety: a systematic review.

OBJECTIVE: The aim of this systematic review was to evaluate all controlled trials of autogenic training (AT) as a means of reducing stress and anxiety levels in human subjects. METHOD: A search for all published and unpublished controlled trials was carried out in the four major databases, specifically CISCOM, Medline, PsychLit and CINAHL. RESULTS: Eight such trials were located, all of which are included here. The majority of trials were methodologically flawed. A range of outcome measures were used, with Spielberger's State-Trait Anxiety Inventory being the most popular. Deviations from the accepted technique of AT were conspicuous and trials using the classical AT were in the minority. Seven trials reported positive effects of AT in reducing stress. One study showed no such benefit. Since one trial had used AT in combination with another technique, visual imagery, no conclusion can be drawn about the effect of AT in this case. CONCLUSION: No firm conclusions could be drawn from this systematic review. AT, properly applied, remains to be tested in controlled trials that are appropriately planned and executed.

Anxiety↗

PubMed2001

Complex proximal humeral fractures in adults--a systematic review of management.

We performed a systematic review of the literature to compare the clinical outcomes of the management of three and four part fractures of the proximal humerus by conservative regimes, internal and external fixations and arthroplasty. We identified 147 reports of comparative trials and case series between 1969 and 1999. We selected only studies dealing exclusively with three and four part fractures of the proximal humerus, with at least 15 patients, treated within 48 h of injury by one of the three modalities studied, in which at least one of the outcomes of interest (pain, range of motion, infection and restoration of anatomy) was described. Also, to be included, studies had to have a follow-up period of at least 6 months, in which a minimum of 85% of patients were followed-up. Twenty four reports met our eligibility criteria. Conservatively managed patients had more pain and a poorer range of motion than those managed by either fixation or arthroplasty. Better restoration of anatomy was delivered in the fixation group. There was no significant difference in the functional range of motion between the arthroplasty and fixation groups, but there were very few studies available to compare infection rates in these two management modalities. The results from the present systematic review suggest that the data from the published literature are inadequate for evidence-based decision making with regards to the treatment of complex proximal humeral fractures.

Arthroplasty↗

PubMed2026

Nurse-led acute care post-operative interventions in adult cardiac surgery: a systematic review.

AIMS: The primary aim of this systematic review was to identify nurse-led clinical interventions evaluated in randomized controlled trials (RCTs) for adults who had undergone cardiac surgery. The secondary aim was to assess the effectiveness of these interventions on post-operative clinical and patient-reported outcomes during the acute inpatient phase. METHODS AND RESULTS: A systematic review was undertaken according to an a priori protocol using Joanna Briggs Institute (JBI) methodology and PRISMA guideline for reporting. Eligible studies were RCTs of adult (≥18 years) cardiac surgery, nurse-led inpatient interventions implemented immediately post-surgery and prior to discharge. Six databases were searched from inception to June 2025. Of 2690 records, 19 RCTs were eligible, representing 13 countries, and 3142 participants. Risk of bias varied, with only two low-risk trials. Interventions were grouped into seven domains: behavioural support; temperature management and comfort strategies; pain and symptom management; wound care; infection prevention; respiratory and pulmonary function; and post-operative recovery, mobilization, and hydration. Across these domains, nurse-led interventions were generally feasible, safe, and positively affected patient comfort, physiological stability, symptom relief, and aspects of functional recovery. CONCLUSION: Nurse-led inpatient interventions contribute meaningfully to inpatient post-operative recovery in cardiac surgery, although the broader cardiac surgical nursing scope is underrepresented in RCTs. This review provides a foundation for developing further high-quality research, peer-reviewed interdisciplinary practice guidelines, and strengthening the scope and recognition of cardiac surgical nursing as a distinct specialty. REGISTRATION: PROSPERO-CRD420251063851.

Humans↗

PubMedDate not supplied

Prophylactic ephedrine prevents hypotension during spinal anesthesia for Cesarean delivery but does not improve neonatal outcome: a quantitative systematic review.

PURPOSE: The objective of this systematic review was to assess the effectiveness and safety of ephedrine compared with control when given prophylactically to prevent hypotension during spinal anesthesia for Cesarean delivery. SOURCE: Randomized, controlled trials obtained through MEDLINE, EMBASE, the Cochrane Controlled Trials Registry, contact with leading experts, and a reference list of published articles were analyzed. The following keywords were utilized: spinal anesthesia, hypotension, Cesarean section, pregnancy complications, pregnancy outcome, fetal outcome, neonatal outcome, umbilical blood cord gases, vasopressor and ephedrine. Clinical trials were considered if they compared prophylactic ephedrine, given by any dose or route, vs control. PRINCIPAL FINDINGS: The 14 clinical trials identified included data from a total of 641 patients. Ephedrine was more effective than control for preventing hypotension (relative risk [RR], 0.73; 95% confidence interval [CI], 0.63 to 0.86). Most importantly, there was no difference in the risk of fetal acidosis, defined as umbilical arterial pH < 7.2 (RR, 1.36; 95% CI, 0.55 to 3.35) or the incidence of low Apgar scores (< 7 or < 8) at one minute (RR, 0.77; 95% CI, 0.29 to 2.06) and five minutes (RR, 0.72; 95% CI, 0.24 to 2.19). CONCLUSIONS: Prophylactic ephedrine is more effective than control for preventing hypotension during spinal anesthesia for elective Cesarean delivery but a clinically relevant positive effect on neonatal outcome was not observed. Therefore, the routine use of prophylactic ephedrine to prevent any adverse effects of maternal hypotension following spinal anesthesia for Cesarean delivery is not supported by the current systematic review.

Acidosis↗

PubMed1999

The treatment of tardive dyskinesia--a systematic review and meta-analysis.

This systematic review aimed to collate randomized controlled trials (RCTs) of various interventions used to treat tardive dyskinesia (TD) and, where appropriate, to combine the data for meta-analysis. Clinical trials were identified by electronic searches, handsearches and contact with principal investigators. Data were extracted independently by two reviewers, for outcomes related to improvement, deterioration, side-effects and drop out rates. Data were pooled using the Mantel-Haenzel Odds Ratio (fixed effect model). For treatments that had significant effects, the number needed to treat (NNT) was calculated. From 296 controlled clinical trials, data were extracted from 47 trials. For most interventions, we could identify no RCT-derived evidence of efficacy. A meta-analysis showed that baclofen, deanol and diazepam were no more effective than a placebo. Single RCTs demonstrated a lack of evidence of any effect for bromocriptine, ceruletide, clonidine, estrogen, gamma linolenic acid, hydergine, lecithin, lithium, progabide, seligiline and tetrahydroisoxazolopyridinol. The meta-analysis found that five interventions were effective: L-dopa, oxypertine, sodium valproate, tiapride and vitamin E; neuroleptic reduction was marginally significant. Data from single RCTs revealed that insulin, alpha methyl dopa and reserpine were more effective than a placebo. There was a significantly increased risk of adverse events associated with baclofen, deanol, L-dopa, oxypertine and reserpine. Meta-analysis of the impact of placebo (n=485) showed that 37.3% of participants showed an improvement. Interpretation of this systematic review requires caution as the individual trials identified tended to have small sample sizes. For many compounds, data from only one trial were available, and where meta-analyses were possible, these were based on a small number of trials. Despite these concerns, the review facilitated the interpretation of the large and diverse range of treatments used for TD. Clinical recommendations for the treatment of TD are made, based on the availability of RCT-derived evidence, the strength of that evidence and the presence of adverse effects.

Double-Blind Method↗

PubMed2005

Enteral nutritional support in prevention and treatment of pressure ulcers: a systematic review and meta-analysis.

BACKGROUND: There have been few systematic reviews and no meta-analyses of the clinical benefits of nutritional support in patients with, or at risk of developing, pressure ulcers. Therefore, this systematic review and meta-analysis was undertaken to address the impact of enteral nutritional support on pressure ulcer incidence and healing and a range of other clinically relevant outcome measures in this group. METHODS: Fifteen studies (including eight randomised controlled trials (RCTs)) of oral nutritional supplements (ONS) or enteral tube feeding (ETF), identified using electronic databases (including Pub Med and Cochrane) and bibliography searches, were included in the systematic review. Outcomes including pressure ulcer incidence, pressure ulcer healing, quality of life, complications, mortality, anthropometry and dietary intake were recorded, with the aim of comparing nutritional support versus routine care (e.g. usual diet and pressure ulcer care) and nutritional formulas of different composition. Of these 15 studies, 5 RCTs comparing ONS (4 RCTs) and ETF (1 RCT) with routine care could be included in a meta-analysis of pressure ulcer incidence. RESULTS: Meta-analysis showed that ONS (250-500 kcal, 2-26 weeks) were associated with a significantly lower incidence of pressure ulcer development in at-risk patients compared to routine care (odds ratio 0.75, 95% CI 0.62-0.89, 4 RCTs, n=1224, elderly, post-surgical, chronically hospitalised patients). Similar results were obtained when a combined meta-analysis of ONS (4 RCT) and ETF (1 RCT) trials was performed (OR 0.74, 95% CI 0.62-0.88, 5 RCTs, n=1325). Individual studies showed a trend towards improved healing of existing pressure ulcers with disease-specific (including high protein) versus standard formulas, although robust RCTs are required to confirm this. Although some studies indicate that total nutritional intake is improved, data on other outcome measures (quality of life) are lacking. CONCLUSIONS: This systematic review shows enteral nutritional support, particularly high protein ONS, can significantly reduce the risk of developing pressure ulcers (by 25%). Although studies suggest ONS and ETF may improve healing of PU, further research to confirm this trend is required.

Aged↗

PubMed2006

The association between head and cervical posture and temporomandibular disorders: a systematic review.

AIMS: To carry out a systematic review to assess the evidence concerning the association between head and cervical posture and temporomandibular disorders (TMD). METHODS: A search of Medline, Pubmed, Embase, Web of Science, Lilacs, and Cochrane Library databases was conducted in all languages with the help of a health sciences librarian. Key words used in the search were posture, head posture, cervical spine or neck, vertebrae, cervical lordosis, craniomandibular disorders or temporomandibular disorders, temporomandibular disorders, and orofacial pain or facial pain. Abstracts which appeared to fulfill the initial selection criteria were selected by consensus. The original articles were retrieved and evaluated to ensure they met the inclusion criteria. A methodological checklist was used to evaluate the quality of the selected articles and their references were hand-searched for possible missing articles. RESULTS: Twelve studies met all inclusion criteria and were analyzed in detail for their methodology and information quality. Nine articles that analyzed the association between head posture and TMD included patients with mixed TMD diagnosis; 1 article differentiated among muscular, articular, and mixed symptomatology; and 3 articles analyzed information from patients with only articular problems. Finally, 2 studies evaluated the association between head posture and TMD in patients with muscular TMD. Several methodological defects were noted in the 12 studies. CONCLUSION: Since most of the studies included in this systematic review were of poor methodological quality, the findings of the studies should be interpreted with caution. The association between intra-articular and muscular TMD and head and cervical posture is still unclear, and better controlled studies with comprehensive TMD diagnoses, greater sample sizes, and objective posture evaluation are necessary.

Head↗

PubMed1999

Evidence-based psychopharmacology 2. Appraising a systematic review: is risperidone better than conventional antipsychotics in the treatment of schizophrenia?

Systematic reviews are increasingly used to combine the results of several studies in order to define the treatment effect with a high degree of precision. However, reviews of this nature may lead to spurious results and should not be accepted uncritically. This article, the second in a series on evidence-based psychopharmacology, is intended to illustrate the process of critical appraisal of a systematic review. In this example, a systematic review of studies comparing risperidone with conventional antipsychotics is appraised. Interpretation of the results of the systematic review may be hampered by the way in which studies were selected.

Adult↗

PubMed2003

Updated method guidelines for systematic reviews in the cochrane collaboration back review group.

STUDY DESIGN: Descriptive method guidelines. OBJECTIVES: To help reviewers design, conduct, and report reviews of trials in the field of back and neck pain. SUMMARY OF BACKGROUND DATA: In 1997, the Cochrane Collaboration Back Review Group published method guidelines for systematic reviews. Since its publication, new methodologic evidence emerged and more experience was acquired in conducting reviews. METHODS: All reviews and protocols of the Back Review Group were assessed for compliance with the 1997 method guidelines. Also, the most recent version of the Cochrane Handbook (4.1) was checked for new recommendations. In addition, some important topics that were not addressed in the 1997 method guidelines were included (e.g., methods for qualitative analysis, reporting of conclusions, and discussion of clinical relevance of the results). In May 2002, preliminary results were presented and discussed in a workshop. In two rounds, a list of all possible recommendations and the final draft were circulated for comments among the editors of the Back Review Group. RESULTS: The recommendations are divided in five categories: literature search, inclusion criteria, methodologic quality assessment, data extraction, and data analysis. Each recommendation is classified in minimum criteria and further guidance. Additional recommendations are included regarding assessment of clinical relevance, and reporting of results and conclusions. CONCLUSIONS: Systematic reviews need to be conducted as carefully as the trials they report and, to achieve full impact, systematic reviews need to meet high methodologic standards.

Back Pain↗

PubMed2026

Educational interventions to improve medical students' bad news communication skills: A systematic review and meta-analysis.

OBJECTIVES: This systematic review aimed to both determine whether educational interventions improve medical students' ability and/or confidence in Bad News Communication (BNC), as well as assess the relative efficacy of instructional formats. METHODS: Performed according to the PRISMA guidelines, four databases were searched for articles describing education-based interventions to improve medical student's BNC ability and/or confidence, published in English between 2001 and 2024. Data on students' self-reported or observer-assessed level of competence/ability in BNC (primary outcome), and students' self-assessed confidence in BNC skills (secondary outcomes), were analysed. Meta regression explained the influence of several categorical moderators on heterogeneity in relation to intervention effects on competence/ability. RESULTS: 27 studies met the criteria for inclusion in the systematic review and 17 studies for the meta-analysis. Interventions described in controlled studies were associated with a moderate and significant increase in BNC ability (13 data sets; standardized mean difference [SMD] = 1.09, 95% CI = 0.52 - 1.66). Interventions detailed in pre-post design studies were associated with a significant increase in BNC ability (20 data sets; SMD = 0.92, 95% CI = 0.52 - 1.32), and student confidence/comfort in their BNC skills (12 data sets; SMD = 1.16, 95% CI = 0.57 - 1.75). Subgroup analysis demonstrated better skills/competence outcomes in studies that included simulation-based training (SBT). CONCLUSIONS: Educational interventions improve the BNC ability and confidence of medical students. Interventions should include an SBT element as this leads to greater improvements in BNC ability. Further research is needed to determine to what extent these interventions translate to positive patient outcomes. PRACTICE IMPLICATIONS: Diverse educational programme, especially those including simulation-based training, are effective in improving BNC skills, although the longetivity of these improvements is at present unclear. Therefore, we recommend that refresher courses or practice opportunities should be scheduled throughout students' medical education to ensure retention of BNC skills.

Humans↗

PubMed1998

Use of systematic reviews of randomised trials by Australian neonatologists and obstetricians.

OBJECTIVE: To determine what proportion of Australian neonatologists and obstetricians report using systematic reviews of randomised trials. DESIGN: Cross-sectional survey using structured telephone interviews. SETTING: Australian clinical practice in 1995. PARTICIPANTS: 103 of the 104 neonatologists in Australia (defined as clinicians holding a position in a neonatal intensive care unit); a random sample of 145 members of the Royal Australian College of Obstetricians and Gynaecologists currently practising in Australia. MAIN OUTCOME MEASURES: Information sources used in clinical practice; reported awareness of, access to and use of systematic reviews, and consequent practice changes. RESULTS: Response rates were 95% (neonatologists) and 87% (obstetricians); 71 neonatologists (72%) and 55 obstetricians (44%) reported using systematic reviews, primarily for individual patient care. Databases of systematic reviews were used with a median frequency of once per month. Among neonatologists, systematic reviews were used more commonly by those who were familiar with computers, attended professional meetings, and had authored research papers. Among obstetricians, they were used more commonly by those who were familiar with computers, had less than 10 years' clinical experience, attended more deliveries, and were full-time staff specialists in public hospitals. Of neonatologists who reported using systematic reviews, 58% attributed some practice change to this use. For obstetricians, the corresponding figure was 80%. CONCLUSIONS: There is evidence that Australian neonatologists and obstetricians use systematic reviews and modify their practice accordingly. Dissemination efforts can benefit from knowledge of factors that predict use of systematic reviews.

Adult↗

PubMed2005

Are health care providers who work with cancer drugs at an increased risk for toxic events? A systematic review and meta-analysis of the literature.

OBJECTIVE: A systematic review and meta-analysis was conducted to test the hypothesis that oncology health care workers are at an increased risk of cancer, reproductive complications and acute toxic events. DESIGN: A structured literature search of Index Medicus/ MEDLINE, CINAHL, EMBASE, the Cochrane Database of Systematic Reviews and Healthstar was performed from 1966 to December 2004 for human epidemiological studies evaluating the risk of toxic events in health care workers exposed to cytotoxic drugs. Raw data and adjusted odds ratios (OR) reported in eligible studies were combined using a random effects model to calculate point estimates and 95% confidence intervals (CI) for each potential risk outcome. MAIN OUTCOME MEASURES: Adjusted OR for congenital malformations, stillbirths and spontaneous abortions among health care workers exposure to cytotoxic agents compared to a nonexposed control group. RESULTS: The systematic review identified 14 studies evaluating the outcomes of interest, seven of which were suitable for statistical pooling. Due to lack of evidence, we were unable to estimate a pooled OR for the risk of cancer and acute toxic events. However, no significant association was detected between exposure to cytotoxic drugs and; congenital malformations (OR = 1.64; 95% CI: 0.91-2.94) and stillbirths (OR = 1.16; 95% CI: 0.73-1.82). In contrast, an association was identified between exposure to chemotherapy and spontaneous abortions (OR = 1.46; 95% CI: 1.11-1.92). CONCLUSIONS: The results of this systematic review identified a small incremental risk for spontaneous abortions in female staff working with cytotoxic agents. Health policy decision makers should effectively communicate the magnitude of this risk to their staff and implement cost effective interventions for its reduction or elimination.

Abortion, Spontaneous↗

PubMed2002

Reviews of acupuncture for chronic neck pain: pitfalls in conducting systematic reviews.

This paper examines some of the problems specifically associated with conducting research into acupuncture and how this can lead to further problems with subsequent systematic reviews. Studies for the treatment of chronic neck pain have been used as examples of how presented information can be misleading to an acupuncture-naive reader and how researchers must be sensitive to these problems when compiling their inclusion and exclusion criteria. The problems associated with scoring trials are discussed and further work to increase the scope of scoring mechanisms is recommended in order to produce meaningful systematic reviews in the future.

Acupuncture Therapy↗

PubMed2005

Realist review--a new method of systematic review designed for complex policy interventions.

Evidence-based policy is a dominant theme in contemporary public services but the practical realities and challenges involved in using evidence in policy-making are formidable. Part of the problem is one of complexity. In health services and other public services, we are dealing with complex social interventions which act on complex social systems--things like league tables, performance measures, regulation and inspection, or funding reforms. These are not 'magic bullets' which will always hit their target, but programmes whose effects are crucially dependent on context and implementation. Traditional methods of review focus on measuring and reporting on programme effectiveness, often find that the evidence is mixed or conflicting, and provide little or no clue as to why the intervention worked or did not work when applied in different contexts or circumstances, deployed by different stakeholders, or used for different purposes. This paper offers a model of research synthesis which is designed to work with complex social interventions or programmes, and which is based on the emerging 'realist' approach to evaluation. It provides an explanatory analysis aimed at discerning what works for whom, in what circumstances, in what respects and how. The first step is to make explicit the programme theory (or theories)--the underlying assumptions about how an intervention is meant to work and what impacts it is expected to have. We then look for empirical evidence to populate this theoretical framework, supporting, contradicting or modifying the programme theories as it goes. The results of the review combine theoretical understanding and empirical evidence, and focus on explaining the relationship between the context in which the intervention is applied, the mechanisms by which it works and the outcomes which are produced. The aim is to enable decision-makers to reach a deeper understanding of the intervention and how it can be made to work most effectively. Realist review does not provide simple answers to complex questions. It will not tell policy-makers or managers whether something works or not, but will provide the policy and practice community with the kind of rich, detailed and highly practical understanding of complex social interventions which is likely to be of much more use to them when planning and implementing programmes at a national, regional or local level.

Evaluation Studies as Topic↗

PubMed2006

Method guidelines for Cochrane Musculoskeletal Group systematic reviews.

The Cochrane Musculoskeletal Group (CMSG), one of 50 groups of the not-for-profit international Cochrane Collaboration, prepares, maintains, and disseminates systematic reviews of treatments for musculoskeletal diseases. To enhance the quality and usability of systematic reviews, the CMSG has developed tailored methodological guidelines for authors of CMSG systematic reviews. Recommendations specific to musculoskeletal disorders are provided for various aspects of undertaking a systematic review, including literature searching, inclusion criteria, quality assessment, grading of evidence, data collection, and data analysis. These guidelines will help researchers design, conduct, and report results of systematic reviews of trials in the following fields of musculoskeletal health: gout, osteoarthritis, osteoporosis, pediatric rheumatology, rheumatoid arthritis, soft tissue rheumatism, spondyloarthropathy, systemic lupus erythematosus, systemic sclerosis, and vasculitis. Systematic reviews need to be conducted according to high methodological standards. These recommendations on developing and performing a systematic review will help improve consistency among CMSG reviews.

Clinical Trials as Topic↗

PubMed2000

Treatments for fatigue in multiple sclerosis: a rapid and systematic review.

BACKGROUND: Multiple sclerosis (MS) is an important problem both for people with the disease and for society. There is no cure, and alleviation of symptoms forms the cornerstone of care. Excessive fatigue that severely limits activity is experienced by at least two-thirds of the estimated 60,000 people with MS in the UK. OBJECTIVES: (1) To identify current treatments for fatigue in MS and their evidence-base. (2) To systematically review the evidence for those treatments that have been investigated in more than one rigorous study, in order to determine their effectiveness and cost-effectiveness. METHODS: The review was carried out in two stages: a formal scoping review (to assess the range of interventions used by people with MS), and a systematic review for treatments that had been identified as promising and that had been investigated in clinical trials (as identified in the scoping review). A systematic review of research on costs and cost-effectiveness of those interventions identified as promising was also performed. Electronic databases, including MEDLINE and EMBASE, were searched for the period 1991-June 1999 (scoping review) and 1966-December 1999 (systematic review). Reference lists from publications were also searched, and experts were contacted for any additional information not already identified. RESULTS: Interventions identified for the treatment of fatigue in MS (1) Behavioural advice. This is the main element of initial clinical management and no rigorous research of its effectiveness was identified. (2) Drugs (amantadine, pemoline, potassium-channel blockers and antidepressants). (3) Training, rehabilitation and devices (cooling vests and electromagnetic fields). (4) Alternative therapies (bee venom, cannabis, acupuncture/acupressure and yoga). Only two drugs, amantadine and pemoline, met the criteria for full systematic review. RESULTS - EFFECTIVENESS OF AMANTADINE: One parallel and three crossover trials were found, involving a total of 236 people with MS. All studies were open to bias. All studies showed a pattern in favour of amantadine compared with placebo, but there is considerable uncertainty about the validity and clinical significance of this finding. This pattern of benefit was considerably undermined when different assumptions were used in the sensitivity analysis. RESULTS - EFFECTIVENESS OF PEMOLINE: One parallel and one crossover trial were found involving a total of 126 people with MS. Both studies were open to bias. There was no overall tendency in favour of pemoline over placebo and an excess of reports of adverse effects with pemoline. RESULTS - HEALTH ECONOMIC ANALYSIS: The drug costs of amantadine and pemoline are modest (pound 200 and pound 80 per annum, respectively). No economic evaluations were identified in the systematic review, and available data were insufficient to allow modelling of cost-effectiveness in this rapid review. CONCLUSIONS: There is insufficient evidence to allow people with MS, clinicians or policy makers to make informed decisions on the appropriate use of the many treatments on offer. Only amantadine appears to have some proven ability to alleviate the fatigue in MS, though only a proportion of users will obtain benefit and then only some of these patients will benefit sufficiently to take the drug in the long term. CONCLUSIONS - RECOMMENDATIONS FOR RESEARCH: The frequency, severity and impact of fatigue, the poverty of available research, and the absence of any ongoing research, suggest that new research is an urgent priority. People with MS, clinicians and policy makers should work together to ensure that the evidence required is collected as quickly as possible by encouraging involvement in rigorous research. Research should not be restricted to the two drugs reviewed in depth in this report. All interventions identified in the scoping review (see above) should be considered, as should basic scientific research into the underlying mechanism of fatigue in MS.

Amantadine↗