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PubMed2000

Short-term low-dose corticosteroids vs placebo and nonsteroidal antiinflammatory drugs in rheumatoid arthritis.

BACKGROUND: The effect of low dose corticosteroids, equivalent to 15 mg prednisolone daily or less, in patients with rheumatoid arthritis has been questioned. We therefore performed a systematic review of trials which compared corticosteroids with placebo or non-steroidal, anti-inflammatory drugs. OBJECTIVES: To determine whether short-term (i.e. as recorded within the first month of therapy), oral low-dose corticosteroids (corresponding to a maximum of 15 mg prednisolone daily) is superior to placebo and nonsteroidal, antiinflammatory drugs in patients with rheumatoid arthritis. SEARCH STRATEGY: Medline Silverplatter, The Cochrane Controlled Trials Register, reference lists and a personal archive. SELECTION CRITERIA: All randomised studies comparing an oral corticosteroid (not exceeding an equivalent of 15 mg prednisolone daily) with placebo or a nonsteroidal, antiinflammatory drug were eligible if they reported clinical outcomes within one month after start of therapy. DATA COLLECTION AND ANALYSIS: Decisions on which trials to include were made independently by two observers based on the methods sections of the trials only. Standardised effect measures were used for the statistical analyses; the random effects model was used if P<0.10 for the test of heterogeneity. MAIN RESULTS: Ten studies, involving 320 patients, were included in the meta-analysis. Prednisolone had a marked effect over placebo on joint tenderness (standardised effect size 1.31, 95% confidence interval 0.78 to 1.83), pain (standardised effect size 1.75, 0.87 to 2.64) and grip strength (standardised effect size 0.41, 0.13 to 0.69). Measured in the original units, the differences were 12 tender joints (6 to 18) and 22 mm Hg (5 to 40) for grip strength. Prednisolone also had a greater effect than nonsteroidal, antiinflammatory drugs on joint tenderness (standardised effect size 0.63, 0.11 to 1.16) and pain (standardised effect size 1.25, 0.26 to 2.24), whereas the difference in grip strength was not significant (standardised effect size 0.31, -0.02 to 0.64). Measured in the original units, the differences were 9 tender joints (5 to 12) and 12 mm Hg (-6 to 31). The risk of adverse effects, also during moderate- and long-term use, seemed acceptable. REVIEWER'S CONCLUSIONS: Prednisolone in low doses (not exceeding 15 mg daily) may be used intermittently in patients with rheumatoid arthritis, particularly if the disease cannot be controlled by other means. Since prednisolone is highly effective, short-term placebo controlled trials studying the clinical effect of low-dose prednisolone or other oral corticosteroids are no longer necessary.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2001

Systematic reviews: the heart of evidence-based practice.

Research utilization approaches in nursing recently have been replaced by evidence-based practice (EBP) approaches. The heart of the new EBP paradigm is the systematic review. Systematic reviews are carefully synthesized research evidence designed to answer focused clinical questions. Systematic reviews (also known as evidence summaries and integrative reviews) implement recently developed scientific methods to summarize results from multiple research studies. Specific strategies are required for success in locating systematic reviews. Major sources of systematic reviews for use by advanced practice nurses in acute and critical care are the Online Journal of Knowledge Synthesis for Nursing, Agency for Healthcare Research and Quality, and the Cochrane Library. This discussion describes systematic reviews as the pivotal point in today's paradigm of EBP and guides the advanced practice nurse in locating and accessing systematic reviews for use in practice.

Evidence-Based Medicine↗

PubMed2004

Individual patient data meta-analyses.

Systematic reviews help people to make well-informed decisions about health care by bringing together the relevant evidence, appraising it and, where appropriate, combining it in a meta-analysis. The ultimate aim for a systematic review should be to present all relevant data on all participants in all research judged to be eligible for the review. In reviews of the effects of interventions, this ultimate aim would be met through the collection and analyses of the results of all relevant randomized trials. Reviews that use individual patient data achieve this by the central collection and analyses of data on each participant in the trials. It allows the reviewer to overcome many of the problems associated with a reliance on published data alone, and some of the problems associated with using aggregate data supplied by the trialist, and will add to the analyses that can be performed. This chapter discusses the rationale for individual patient data reviews and describes some of their features.

Data Collection↗

PubMed2026

Artificial intelligence for dental caries detection: An umbrella review.

Artificial intelligence (AI) has been proposed as a tool to improve dental caries detection across imaging modalities; however, its clinical value remains uncertain. This umbrella review aimed to synthesize and critically appraise systematic reviews evaluating AI for caries detection and diagnosis. An umbrella review was conducted following PRIOR guidance (PROSPERO CRD420261340728). Searches were performed in MEDLINE, Embase, Scopus, Web of Science, and Google Scholar up to 15 March 2026. Methodological quality was assessed using AMSTAR 2, and overlap of primary studies was quantified using the corrected covered area (CCA). Seventeen systematic reviews were included, of which five reported diagnostic test accuracy meta-analyses using bivariate or HSROC models. Across these meta-analyses, pooled sensitivity ranged from 0.76 to 0.94 and specificity from 0.85 to 0.91. Most systems were based on deep learning models applied to bitewing radiographs and intraoral photographs. However, substantial heterogeneity was observed in imaging modalities, lesion thresholds, analytical tasks, and evaluation metrics. In addition, a high degree of overlap across reviews and recurrent methodological limitations, including reliance on retrospective datasets, limited external validation, and inconsistent reporting, substantially weaken the reliability of the evidence. Although AI models demonstrate high diagnostic performance under experimental conditions, current evidence does not support their use as stand-alone diagnostic tools. Their clinical applicability remains limited, and implementation should be restricted to decision-support contexts until robust prospective validation demonstrates meaningful impact on clinical decision-making and patient outcomes.

Dental Caries↗

PubMed2001

Systematic review in diagnostic radiology.

Systematic review (SR) already makes a major contribution to evidence-based healthcare by making the review process transparent and by reducing bias. SR has been successfully applied to observational studies. Radiologists have already begun to make an impact in dentistry by using SR as a decision-making tool. Central to SR is establishment of a research question, selection criteria, a search plan, a literature search, an appraisal of the identified literature by the selection criteria; an analysis and a formulation of recommendations. With regard to the literature search, electronic databases (Medline, Embase, Science Citation Index, Lilacs), controlled subject headings, exploding and free-text searching, handsearching and the gray literature are discussed.

Databases, Bibliographic↗

PubMed2005

What is the most cost-effective treatment for patients with low back pain? A systematic review.

Economic evaluations of the various interventions available for low back pain will help clinicians and policymakers to identify the most beneficial treatment. This chapter aims to evaluate the most cost-effective treatments for patients with non-specific low back pain. Pubmed, Embase and the Cochrane library were used to search for articles published from 1966 to July 2004 using a variety of keywords. References were checked to identify additional studies. The consensus health economic criteria (CHEC) list was used to assess the methodological quality of the studies. We found 17 studies; six of these concluded that the intervention of interest was superior to the control intervention. However, definite conclusions about the most cost-effective intervention could not be drawn because of the heterogeneity of interventions, controls and study populations. More high-quality economic evaluations are needed before such a conclusion can be made.

Cost-Benefit Analysis↗

PubMed2006

Compliance with QUOROM and quality of reporting of overlapping meta-analyses on the role of acetylcysteine in the prevention of contrast associated nephropathy: case study.

OBJECTIVE: To appraise multiple systematic reviews on the same clinical topic, focusing on predictors and correlates of quality of reporting of meta-analysis (QUOROM) scores. DESIGN: Case study. SETTING: Reviews providing at least individual quantitative estimates on role of acetylcysteine in the prevention of contrast associated nephropathy. DATA SOURCES: PubMed, the database of abstracts of reviews of effects, and the Cochrane database of systematic reviews (updated March 2005). MAIN OUTCOME MEASURES: Funding, compliance with the QUOROM checklist, scores on the Oxman and Guyatt quality index, and authors' recommendations. RESULTS: 10 systematic reviews, published August 2003 to March 2005, were included. Nine pooled events despite heterogeneity and five recommended routine use of acetylcysteine, whereas the remaining studies called for further research. Compliance with the 18 items on the QUOROM checklist was relatively high (median 16, range 11 to 17), although shorter manuscripts had significantly lower scores (R = 0.73; P = 0.016). Reviewers who reported previous not for profit funding were more likely to score higher on the Oxman and Guyatt quality index. No association was found between QUOROM and Oxman and Guyatt scores (R = -0.06; P = 0.86), mainly because of greater emphasis of the Oxman and Guyatt scores on the appraisal of bias in selection and validity assessment (inadequate in five reviews). CONCLUSIONS: Multiple systematic reviews on the same clinical topic varied in quality of reporting and recommendations. Longer manuscripts and previous not for profit funding were associated with higher quality.

Acetylcysteine↗

PubMed2006

The process of systematic review and its application in agri-food public-health.

Foodborne illness is an important public-health concern. Livestock operations represent the original source of many foodborne pathogens. Policy- and decision-makers in the area of agri-food public-health need dependable information on interventions to reduce foodborne diseases. While individual studies might be weak or reach contradictory conclusions, the body of information contained in all studies might reveal a clearer picture of the state of knowledge. A formal process has been developed for conducting systematic reviews of the human healthcare literature. Systematic reviews differ from traditional narrative reviews in that systematic reviews follow a structured research protocol to reduce sources of bias at all stages of the review. This includes the objective, the literature search, the identification of relevant literature, quality assessment of relevant studies, summarization or statistical analysis of data, and conclusions. To date, systematic reviews have not been widely used in agri-food public-health. Existing systematic reviews on agri-food public-health topics revealed a scarcity of rigorously conducted intervention research, indicating a need for additional high quality primary studies. The specific protocols used to conduct systematic reviews in agri-food public-health need to accommodate the use of challenge studies and observational studies, the lack of randomized controlled trials, and the clustering of animal populations.

Animals↗

PubMed2026

Cardiovascular risks in psychiatric disorders and psychiatric risks in cardiovascular disorders: implications for prevention and clinical management - a large-scale umbrella review encompassing 76 meta-analyses.

OBJECTIVE: Psychiatric and cardiovascular disorders often co-occur, complicating their assessment and management. No umbrella review(UR) has summarized the meta-analytic evidence on the co-occurrence of psychiatric and cardiovascular disorders and assessed its credibility. METHODS: Meta-analytic systematic reviews of observational studies documenting the prevalence, risk factors, and outcomes associated with the co-occurrence of cardiovascular and psychiatric disorders, indexed from inception through March.16.2026, and meeting established diagnostic criteria, were included. Meta-analytic association and prevalence estimates were recalculated and graded based on established or adapted criteria. The AMSTAR-2 assessed the quality of the meta-analyses, while several subgroup analyses and meta-regressions aimed to explain the heterogeneity. RESULTS: We included 76 meta-analyses yielding 131 meta-analytic estimates. Based on pre-existing meta-analytic evidence, 22/24 prevalence estimates (91.7%) met moderate/strong credibility criteria. Strong credibility emerged for: orthostatic hypotension in Lewy body(58%;95%C.I. = 50-66%) and Alzheimer's dementias(28.0% = 95%C.I. = 17.0-40.0%); pericardial effusion in anorexia nervosa(25.0%;95%C.I. = 17.0-34.0%); in heart failure(HF): major depressive disorder(MDD)(41.9%;95%C.I. = 36.7-47.1%), mild cognitive impairment(MCI)(41.4%;95%C.I. = 38.3-45.6%), anxiety(32.0%;95%C.I. = 26.5-37.6%), MDD + anxiety(24.7%;95%C.I. = 17.9-34.3%), and dementia(19.8%;95%C.I. = 12.9-27.8%); in atrial fibrillation(AF): MCI(26.0%;95%C.I. = 21.0-30.0%), anxiety in patients undergoing pulmonary vein isolation(PVI)(25.0%;95%C.I. = 12.0-46.0%), MDD in PVI patients (20.0%;95%C.I. = 13.0-29.0%); in coronary artery disease: MDD + anxiety(19.8%;95%C.I. = 16.0-24.6%): in schizophrenia spectrum disorders: clozapine-associated-cardiomyopathy(0.6%;95%C.I. = 0.2-2.3%); clozapine-associated-cardiomyopathy absolute death rates (0.0003;95%C.I. = 0.0001-0.0012); clozapine-associated-cardiomyopathy case fatality rate (0.078;95%C.I. = 0.018-0.285). Several additional disorders were multimorbid in>5% of people, yet with a lower credibility rating. No re-pooled risk factors/outcomes reached strong credibility criteria. CONCLUSIONS: The present study provides an atlas of cardiovascular and psychiatric multimorbidity across varying levels of credibility, reinforcing the need for an integrated, multidisciplinary approach to patient care and for more research on actionable risk/protective factors and outcomes.

Humans↗

PubMed2002

Screening for depression: recommendations and rationale.

This statement summarizes the current U.S. Preventive Services Task Force (USPSTF) recommendations for screening for depression and the supporting scientific evidence and updates the 1996 USPSTF recommendations on this topic. At that time, the USPSTF concluded that there was insufficient evidence to recommend for or against routine use of standardized questionnaires to screen for depression in primary care patients. The complete information on which the current statement is based, including evidence tables and references, is available in the accompanying article in this issue and in the systematic evidence review on this topic, which can be obtained through the USPSTF Web site (http://www.ahrq.gov/clinic/uspstfix.htm) and in print through the Agency for Healthcare Research and Quality Publications Clearinghouse (800-358-9295).

Adult↗

PubMed2000

Opioid antagonists for alcohol dependence.

BACKGROUND: The benefits of selective serotonin reuptake inhibitors, disulfiram, and lithium have not been clear for people with alcohol dependence. While the results of many studies have suggested that opioid agonists increase alcohol consumption, others have shown that mu-opioid antagonists and partial agonists reduce alcohol consumption. The results from animal studies suggest that these agents may prevent the reinforcing effects of alcohol consumption. Based on the results of those animal studies, some opioid antagonists, such as, naltrexone, nalmefene, have been studied for their benefits in treating alcohol dependence. OBJECTIVES: To determine the effectiveness of opioid antagonists in attenuating or preventing the recommencement of alcohol consumption in patients with alcohol dependence in comparison to placebo, other medications and psychosocial treatments. In addition, discontinuation rate, death, patient satisfaction, functioning, health-related quality of life and economic outcomes were also evaluated. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE, CINAHL and Cochrane Controlled Trials Register were undertaken. Du Pont Pharmaceutical and Ivax Corporation were contacted for information regarding unpublished trials. The reference lists of the obtained papers were also examined. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs) and clinical control trials (CCTs) were included. Participants were people with alcohol dependence, diagnosed by any set of criteria, except alcohol dependence who were currently abstinent. Naltrexone (NTX), nalmefene (NMF) and other opioid antagonists with/without other biological or psychosocial treatments were examined. A variety of clinical outcomes, for example alcohol consumption, duration of abstinence, were considered. DATA COLLECTION AND ANALYSIS: Two reviewers evaluated and extracted the data independently. The dichotomous data were extracted on an intention-to-treat basis in which the dropouts were assigned as participants with the worst outcomes. The Peto Odds Ratio with the 95% confidence interval was used to assess the dichotomous data. Weighted Mean Difference with 95% confidence interval was used to assess the continuous data. MAIN RESULTS: The short-term (< 3 months) benefits of NTX were shown in three respects, which were number of patients who return to drinking, percentage or number of drinking days and the number of standard drinks of alcohol. However, 6 months after the completion of 12-week NTX treatment, the benefit of decreasing the number of patients who return to drinking were lost. The short-term evidence from a small sample-size study suggested that disulfiram was more effective than NTX in the respects of number of abstinent days, percentage or number of drinking days and number of standard drinks of alcohol. The evidence from another small sample-size study also suggested that NTX plus an aversive agent was superior to an aversive agent alone in the respect of number of patients who return to drinking in short-, medium-, and long-term treatment. From two short-term and small sample-size studies, the benefit of NMF was shown only in the respect of number of patients who return to drinking. REVIEWER'S CONCLUSIONS: Due to the limited evidence, the following conclusions should be viewed as tentative. NTX has some benefits for patients with alcohol dependence, but patients' adherence to treatment should be of concern. Psychosocial treatments should be concurrently given with NTX. The optimal duration of NTX treatment is not yet known. Although NTX is available for treating alcohol dependence in many countries, in the respect of cost-effectiveness, disulfiram should still remain as an alternative. Due to the dearth of evidence, at present, the combination of NTX and disulfiram or NMF alone should not be used in everyday clinical practice. Randomised, double-blind, placebo-controlled trials of NTX treatment in patients with alcohol dependence

Alcoholism↗

PubMed2000

The Cochrane Library: a resource for current reviews of clinical evidence.

The Cochrane Library is a tool for physicians and other health care practitioners seeking evidence to inform their decisions. The systematic reviews provide a high-quality synthesis of the current literature, saving time for busy people. To make the library more user-friendly, the collaboration plans to produce a consumer summary for each topic in the Database of Systematic Reviews and a cancer library aimed at the general public. In contrast to some of the questionable health-related resources on the Web, the Cochrane Library is an authoritative reference that can help physicians with everyday treatment decisions. The collaboration's commitment to keeping its resources up to date through vigorous support of reviewers should ensure that it remains a valuable Internet tool for physicians.

Databases as Topic↗

PubMedDate not supplied

[Levels of scientific evidence and strength of clinical recommendations. From trials to guidelines. The Italian Group on Medicine Based on Evidence--(GIMBE)].

Evidence-based medicine is a new paradigm of clinical practice that promotes the collection, interpretation and integration of valid, important and applicable to patients research-derived evidence, and it can improve the efficiency and the effectiveness of health care. Nevertheless research often fails to get in clinical practice, also because the traditional tools used by physicians to solve clinical problems are less reliable as the volume/complexity of medical information and biomedical technology have grown exponentially. New tools are emerging to help physicians: the systematic reviews of randomized controlled trials and the clinical practice guidelines that summarize a great volume of medical knowledge to improve health care. Practice guidelines, with a systematic review or meta-analysis pertaining to a definite health problem, summarize the evidence of clinical trials in clinical recommendation. These combine the strength and heterogeneity of the primary studies with magnitude and precision of the treatment effects as it relates to the minimal clinical benefit. The recommendation may suggest therapeutic intervention when the baseline risk is high or otherwise when the baseline risk is low. The Authors discuss principles of evidence-based medicine, measures of treatment effectiveness, systematic reviews and methods used by experts to graduate the strength of clinical recommendations in producing practice guidelines.

Humans↗

PubMed2000

Antidepressant plus benzodiazepine for major depression.

BACKGROUND: Anxiety frequently coexists with depression. There is no systematic review to show if adding benzodiazepines to antidepressants can bring about any advantage over antidepressants alone in the treatment of depression, although such a combination prescription appears to be widely practiced worldwide OBJECTIVES: To determine whether, among adult patients with major depression, adding benzodiazepines to antidepressants brings about any benefit in terms of symptomatic recovery or side-effects in the short term (less than 8 weeks) and long term (more than 2 months), in comparison with treatment by antidepressants alone. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE, International Pharmaceutical Abstracts, Biological Abstracts, LILACS, PsycLit, the Cochrane Library and the trial register of the Cochrane Depression, Anxiety and Neurosis Group (January 1972 to December 1998), combined with hand searching, reference searching, SciSearch and personal contacts. SELECTION CRITERIA: All randomized controlled trials that compared combined antidepressant-benzodiazepine treatment with antidepressant alone for adult patients with major depression (Feighner criteria, RDC, DSM-III, DSM-III-R, DSM-IV or ICD-10). Exclusion criteria are: antidepressant dosage lower than 100 mg of imipramine or its equivalent daily and duration of trial shorter than 4 weeks. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the eligibility and quality of the studies. Two reviewers independently extracted the data. Standardized weighted mean differences and relative risks were estimated with random effects model. The dropouts were assigned the least favorable outcome. Two sensitivity analyses examined the effect of this assumption as well as the effect of including medium quality studies. Three a priori subgroup analyses were performed with regard to the patients with or without comorbid anxiety and with regard to the types of benzodiazepines tested. MAIN RESULTS: Aggregating nine studies with a total of 679 patients, the combination therapy group was 37% (95%CI: 19 to 51%) less likely to drop out than the antidepressant alone group. The intention-to-treat analysis showed that the former were 63% (18 to 127%) to 38% (15 to 66%) more likely to show response (defined as 50% or greater reduction in the depression scale from baseline) up to 4 weeks. REVIEWER'S CONCLUSIONS: The potential benefits of adding a benzodiazepine to an antidepressant must be balanced judiciously against possible harms including development of dependence and accident proneness, on the one hand, and against continued suffering following no response and drop-out, on the other.

Adult↗

PubMed2000

Routine versus selective antifungal administration for control of fungal infections in patients with cancer.

BACKGROUND: Systemic fungal infection is considered to be an important cause of morbidity and mortality in cancer patients, particularly those with neutropenia. Antifungal drugs are often given prophylactically, or to patients with persistent fever. OBJECTIVES: The objective of this review was to assess the effect of antifungal drugs in cancer patients with neutropenia. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (October 1997), MEDLINE (to September 1997) and the reference lists of articles. We searched the proceedings of the ICAAC, General Meeting of the ASM (from 1990 to 1995), and the 7th European Congress of Clinical Microbiology and Infectious Diseases (1995) and contacted researchers in the field. SELECTION CRITERIA: Randomised trials of amphotericin B, AmBisome, fluconazole, ketoconazole, miconazole, or itraconazole compared with placebo or no treatment in cancer patients with neutropenia. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility, methodological quality and abstracted data. MAIN RESULTS: Twenty-five trials involving 2912 patients were included. In 19 trials, prophylactic or later treatment with antifungal drugs had no effect on mortality (odds ratio 0.92, 95% confidence interval 0.75 to 1.14). Only amphotericin showed a significant benefit (odds ratio 0.58, 95% confidence interval 0.37 to 0.93) based on seven trials, but the studies were small and the difference in number of deaths was only 15. Overall it would be necessary to treat 59 patients (95% confidence interval 37 to 131) with an antifungal drug to prevent one case of fungal invasion in surviving patients, although only amphotericin and fluconazole showed a clear beneficial effect. Antifungal treatment decreased fungal colonisation and the need for additional antifungal therapy, but there was heterogeneity across the trials. REVIEWER'S CONCLUSIONS: Routine prophylactic or later therapy with antifungal drugs in cancer patients with neutropenia does not appear to have a beneficial effect on mortality and only a modest effect on fungal invasion.

Antifungal Agents↗

PubMed2000

Donepezil for mild and moderate Alzheimer's disease.

BACKGROUND: Alzheimer's disease is the most common cause of dementia and is a primary degenerative disease of the brain of unknown cause. Onset is usually late in life with increasing impairment of memory, developing gradually into a global impairment of cognition, orientation, linguistic ability and judgement. The clinical course is accompanied by growing disability and dependency on care. One of the characteristic features of the disease is the widely variable rate of progression seen in different patients. Acetylcholine is an important neurotransmitter associated with memory, and abnormalities in cholinergic neurones (including cell loss) are among the many neurological and neurochemical abnormalities that develop in AD. One approach to lessening the impact of these abnormalities is to inhibit the breakdown of acetylcholine by blocking the relevant enzyme. Tacrine was the first compound approved as a treatment for AD in the US and worked in this way, but caused severe side effects. E2020 (donepezil, Aricept) is a second generation cholinesterase inhibitor and appears to be highly specific, with relatively few side effects. OBJECTIVES: The objective of this review is to assess whether or not donepezil improves the well-being of patients with mild or moderate Alzheimer's disease. SEARCH STRATEGY: The Cochrane Dementia and Cognitive Impairment Group Register of Clinical Trials, was searched using the terms 'donepezil', 'E2020' and 'ARICEPT'. Medline, PsychLIT and EMBASE electronic databases were searched with the above terms. Members of the Donepezil Study Group and Eisai Inc were contacted. SELECTION CRITERIA: All unconfounded, double-blind, randomised controlled trials in which treatment with donepezil was administered for more than a day and compared with placebo in patients with Alzheimer's disease. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers (JSB & DB), pooled where appropriate and possible, and the weighted or standardised mean differences or Peto odds ratios (95%CI) estimated. Where possible, intention-to-treat data were used. MAIN RESULTS: There are 4 included trials, covering treatment of 12 or 24 weeks duration in highly selected patients. The only information available on one trial (Gauthier 1998) is a conference abstract which reports no usable results. Available outcome data cover domains including cognitive function and global clinical state, but data on several important dimensions of outcome are not available. The results of three trials suggest a small beneficial effect of donepezil in improving cognitive function: at a 5mg/day dose, improvements measured -2.6 points (95%CI -3.5 -- -1.8) on weighted mean difference, in the midrange of the 70 point ADAS-Cog scale. The results of two trials show some improvement in global clinical state (assessed by an independent clinician) in those treated with donepezil compared to placebo. The patient's own rating of their Quality of Life showed no benefit of donepezil compared with placebo. There were significantly more withdrawals before the end of treatment from the 10mg/d (but not the 5mg/d) donepezil group compared with placebo, which may have resulted in some overestimation of beneficial changes at 10mg/d in progressively declining characteristics, as last available measures were used in analyses. A variety of adverse effects were recorded, but very few patients left a trial as a direct result of the intervention. REVIEWER'S CONCLUSIONS: In selected patients with mild or moderate Alzheimer's disease treated for periods of 12 or 24 weeks, donepezil produced modest improvements in cognitive function and study clinicians rated global clinical state more positively in treated patients. No improvements were present on patient self-assessed quality of life and data on many important outcomes are not available. The practical importance of these changes to patients and carers is unclear.

Alzheimer Disease↗

PubMed2000

Anti-spasticity agents for multiple sclerosis.

BACKGROUND: Spasticity is a common problem in MS patients causing pain, spasms, loss of function and difficulties in nursing care. A variety of oral and parenteral medications are available. OBJECTIVES: To assess the absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis (MS) patients. SEARCH STRATEGY: Randomised controlled trials (RCTs) of anti-spasticity agents were identified using MEDLINE, EMBASE, bibliographies of relevant articles, personal communication, manual searches of relevant journals and information from drug companies. SELECTION CRITERIA: Double-blind, randomised controlled trials (either placebo-controlled or comparative studies) of at least seven days duration. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data and the findings of the trials were summarised. Missing data were collected by correspondence with principal investigators. A meta-analysis was not performed due to the inadequacy of outcome measures and methodological problems with the studies reviewed. MAIN RESULTS: Twenty-three placebo-controlled studies (using baclofen, dantrolene, tizanidine, botulinum toxin, vigabatrin, prazepam and threonine) and thirteen comparative studies met the selection criteria. Only thirteen of these studies used the Ashworth scale, of which only three of the six placebo-controlled trials and none of the seven comparative studies showed a statistically significant difference between test drugs. Spasms, other symptoms and overall impressions were only assessed using unvalidated scores and results of functional assessments were inconclusive. REVIEWER'S CONCLUSIONS: The absolute and comparative efficacy and tolerability of anti-spasticity agents in multiple sclerosis is poorly documented and no recommendations can be made to guide prescribing. The rationale for treating features of the upper motor neurone syndrome must be better understood and sensitive, validated spasticity measures need to be developed.

Anti-Dyskinesia Agents↗

PubMed2003

Amantadine for fatigue in multiple sclerosis.

BACKGROUND: Fatigue is one of the most common and disabling symptoms of people with Multiple Sclerosis (MS). The effective management of fatigue has an important impact on the patient's functioning, abilities, and quality of life. Although a number of strategies have been devised for reducing fatigue, treatment recommendations are based on a limited amount of scientific evidence. Many textbooks report amantadine as a first-choice drug for MS-related fatigue because of published randomised controlled trials (RCTs) showing some benefit. We performed a systematic review in order to gather existing evidence, and contribute to the topic. OBJECTIVES: To determine the effectiveness and safety of amantadine in reducing fatigue in people with MS. SEARCH STRATEGY: RCTs of amantadine were identified using MEDLINE, EMBASE, bibliographies of relevant articles, personal communications, manual searches of relevant journals, and information from drug companies. SELECTION CRITERIA: Randomised, placebo or other drugs-controlled, double-blind trials of amantadine in MS people with fatigue. DATA COLLECTION AND ANALYSIS: Three reviewers selected studies for inclusion in the review and they extracted the data reported in the original articles. Missing and unclear data were requested by correspondence with the trial's principal investigator. A meta-analysis was not performed due to the inadequacy of available data, heterogeneity of outcome measures. MAIN RESULTS: Out of twelve pertinent publications, four trials met the criteria for inclusion in this review: one study was a parallel arms study, and 3 were crossover trials. The number of randomised participants ranged between 10 and 115, and a total of 236 MS patients had been studied. Overall the quality of the studies considered was poor and all trials were open to bias. All studies reported small and inconstant improvements in fatigue, whereas the clinical relevance of these findings and the impact on patient's functioning and health related quality of life remains undetermined. The number of participants reporting side effects during amantadine therapy ranged from 10% to 57%, without significant differences between treatment and placebo. The side effects reported were generally mild, and discontinuation of the drug due to side effects occurred in less than 10% of the patients. REVIEWER'S CONCLUSIONS: Amantadine treatment is overall well tolerated, however its efficacy in reducing fatigue in people with MS is poorly documented and there is insufficient evidence to make recommendations to guide prescribing. It is advisable to (a) improve knowledge on the underlying mechanisms of MS-related fatigue; (b) achieve an agreement on accurate, reliable and responsive outcome measures of fatigue; (c) perform good quality RCTs.

Amantadine↗