scispace - formally typeset
Search or ask a question

Showing papers by "Cochrane Collaboration published in 2003"


Journal ArticleDOI
TL;DR: A step-by-step explanation—there are just five steps— of the methods behind reviewing, and the quality elements inherent in each step (Box 1).
Abstract: Systematic reviews and meta-analyses are a key element of evidence-based healthcare, yet they remain in some ways mysterious. Why did the authors select certain studies and reject others? What did they do to pool results? How did a bunch of insignificant findings suddenly become significant? This paper, along with a book1 that goes into more detail, demystifies these and other related intrigues. A review earns the adjective systematic if it is based on a clearly formulated question, identifies relevant studies, appraises their quality and summarizes the evidence by use of explicit methodology. It is the explicit and systematic approach that distinguishes systematic reviews from traditional reviews and commentaries. Whenever we use the term review in this paper it will mean a systematic review. Reviews should never be done in any other way. In this paper we provide a step-by-step explanation—there are just five steps—of the methods behind reviewing, and the quality elements inherent in each step (Box 1). For purposes of illustration we use a published review concerning the safety of public water fluoridation, but we must emphasize that our subject is review methodology, not fluoridation.

1,028 citations


Journal ArticleDOI
23 Jul 2003-JAMA
TL;DR: All stakeholders-investigators, research organizations and institutions, journal editors, lawmakers, consumers, and others-must act now, together and in their own domains, to ensure comprehensive registration of clinical trials.
Abstract: That it is not possible to find information about all initiated clinical trials is of international concern. This is a particular worry because scientists tend to publish their positive findings more often than their negative findings (publication bias). A comprehensive register of initiated clinical trials, with each trial assigned a unique identifier, would inform reviewers, physicians, and others (eg, consumers) about which trials had been started and directly address the problem of publication bias. Patients and their clinicians could also know which trials are open for enrollment, thus speeding medical advances. Individuals who participate in clinical trials typically provide consent in the belief that they are contributing to medical knowledge. But if the knowledge gained is never reported, the trust between patients and investigators and that between patients and research ethics review boards are both damaged. Ethical issues are of particular concern if industry is gaining financially from public involvement in trials, but refusing to reciprocate by making information from industry-sponsored trials generally available. All stakeholders-investigators, research organizations and institutions, journal editors, lawmakers, consumers, and others-must act now, together and in their own domains, to ensure comprehensive registration of clinical trials.

426 citations


Journal ArticleDOI
TL;DR: This meta-analysis of randomized clinical trials found that spinal manipulation was more effective than sham therapy but was no more or less effective than general practitioner care, analgesics, physical therapy, exercise, or back school.
Abstract: Background Low back pain is a costly illness for which spinal manipulative therapy is commonly recommended. Previous systematic reviews and practice guidelines have reached discordant results on the effectiveness of this therapy for low back pain. Purpose To resolve the discrepancies related to use of spinal manipulative therapy and to update previous estimates of effectiveness by comparing spinal manipulative therapy with other therapies and then incorporating data from recent high-quality randomized, controlled trials (RCTs) into the analysis. Data sources MEDLINE, EMBASE, CINAHL, the Cochrane Controlled Trials Register, and previous systematic reviews. Study selection Randomized, controlled trials of patients with low back pain that evaluated spinal manipulative therapy with at least 1 day of follow-up and at least one clinically relevant outcome measure. Data extraction Two authors, who served as the reviewers for all stages of the meta-analysis, independently extracted data from unmasked articles. Comparison treatments were classified into the following seven categories: sham, conventional general practitioner care, analgesics, physical therapy, exercises, back school, or a collection of therapies judged to be ineffective or even harmful (traction, corset, bed rest, home care, topical gel, no treatment, diathermy, and minimal massage). Data synthesis Thirty-nine RCTs were identified. Meta-regression models were developed for acute or chronic pain and short-term and long-term pain and function. For patients with acute low back pain, spinal manipulative therapy was superior only to sham therapy (10-mm difference [95% CI, 2 to 17 mm] on a 100-mm visual analogue scale) or therapies judged to be ineffective or even harmful. Spinal manipulative therapy had no statistically or clinically significant advantage over general practitioner care, analgesics, physical therapy, exercises, or back school. Results for patients with chronic low back pain were similar. Radiation of pain, study quality, profession of manipulator, and use of manipulation alone or in combination with other therapies did not affect these results. Conclusions There is no evidence that spinal manipulative therapy is superior to other standard treatments for patients with acute or chronic low back pain.

373 citations


Journal ArticleDOI
TL;DR: Current trials are of low quality and provide insufficient evidence to support the use of rTMS in the treatment of depression, according to a systematic review of randomised controlled trials that compared rT MS with sham in patients with depression.
Abstract: Background Repetitive transcranial magnetic stimulation (rTMS) may be useful in the treatment of depression but results from trials have been inconclusive to date. Aims To assess the efficacy of rTMS in treating depression. Method We conducted a systematic review of randomised controlled trials that compared rTMS with sham in patients with depression. We assessed the quality of design of all studies and conducted a meta-analysis of data from trials with similar rTMS delivery. Results We included a total of 14 trials. The quality of the included studies was low. Pooled analysis using the Hamilton Rating Scale for Depression showed an effect in favour of rTMS compared with sham after 2 weeks of treatment (standardised mean difference=–0.35; 95% CI –0.66 to –0.04), but this was not significant at the 2-week follow-up (standardised mean difference=-0.33; 95% CI –0.84 to 0.17). Conclusions Current trials are of low quality and provide insufficient evidence to support the use of rTMS in the treatment of depression.

304 citations


Journal ArticleDOI
TL;DR: Data from two large trials do not suggest a beneficial effect of screening by breast self-examination whereas there is evidence for harms, and breastSelf-examination cannot be recommended.
Abstract: Background Breast self-examination and clinical breast examination have been promoted for many years as general screening methods to diagnose breast cancer at an early stage in order to decrease morbidity and mortality. The possible benefits and harms remain unclear. Objectives To determine whether screening for breast cancer by regular self-examination or clinical breast examination reduces breast cancer mortality and morbidity. Search methods For this update, the Cochrane Breast Cancer Group Specialised Register, The Cochrane Library and PubMed were searched (October 2007). Selection criteria Randomised clinical trials, including cluster randomised trials. Data collection and analysis Decisions on which trials to include were taken independently by the authors based on the methods of a trial. Disagreements were resolved by discussion. Intention-to-treat analyses were conducted using a fixed-effect model with 95% confidence intervals. Main results Two large population-based studies (388,535 women) from Russia and Shanghai that compared breast self-examination with no intervention were included. There was no statistically significant difference in breast cancer mortality between the groups (relative risk 1.05, 95% confidence interval (CI) 0.90 to 1.24; 587 deaths in total). In Russia, more cancers were found in the breast self-examination group than in the control group (relative risk 1.24, 95% CI 1.09 to 1.41) while this was not the case in Shanghai (relative risk 0.97, 95% CI 0.88 to 1.06). Almost twice as many biopsies (3406) with benign results were performed in the screening groups compared to the control groups (1856) (relative risk 1.88, 95% CI 1.77 to 1.99). One large population-based trial of clinical breast examination combined with breast self-examination was also included. The intervention was discontinued because of poor compliance with follow up and no conclusions could be drawn. Authors' conclusions Data from two large trials do not suggest a beneficial effect of screening by breast self-examination but do suggest increased harm in terms of increased numbers of benign lesions identified and an increased number of biopsies performed. At present, screening by breast self-examination or physical examination cannot be recommended.

300 citations


Journal ArticleDOI
TL;DR: In view of the consistency and extent of the survival benefit for CRT the additional acute toxicity appears to be acceptable, and the lack of data on long-term toxicity needs to be addressed.

285 citations


Journal ArticleDOI
TL;DR: Considering the beneficial effects and the absence of detrimental ones, the use of diets enriched with pharmaconutrients-enriched diets could be recommended in ICU patients requiring enteral feeding.

252 citations


Reference EntryDOI
TL;DR: The effects of folic acid supplementation, with or without vitamin B12, on elderly healthy and demented people, in preventing cognitive impairment or retarding its progress is examined.
Abstract: Background: Folates are vitamins essential to the development of the central nervous system. Insufficient folate activity at the time of conception and early pregnancy can result in congenital neural tube defects. In adult life folate deficiency has been known for decades to produce a characteristic form of anaemia ("megaloblastic"). More recently degrees of folate inadequacy, not severe enough to produce anaemia, have been found to be associated with high blood levels of the amino acid homocysteine. Such degrees of folate inadequacy can arise because of insufficient folates in the diet or because of inefficient absorption or metabolic utilisation of folates due to genetic variations. Conventional criteria for diagnosing folate deficiency may be inadequate for identifying people capable of benefiting from dietary supplementation. High blood levels of homocysteine have been linked with the risk of arterial disease, dementia and Alzheimer's disease. There is therefore interest in whether dietary supplements of folic acid (an artificial chemical analogue of naturally occurring folates) can improve cognitive function of people at risk of cognitive decline associated with ageing or dementia, whether by affecting homocysteine metabolism or through other mechanisms. There is a risk that if folic acid is given to people who have undiagnosed deficiency of vitamin B12 it may lead to neurological damage. Vitamin B12 deficiency produces both an anaemia identical to that of folate deficiency but also causes irreversible damage to the central and peripheral nervous systems. Folic acid will correct the anaemia of vitamin B12 deficiency and so delay diagnosis but will not prevent progression to neurological damage. For this reason trials of folic acid supplements may involve simultaneous administration of vitamin B12. Apparent benefit from folic acid given in the combination would therefore need to be "corrected" for any effect of vitamin B12 alone. A separate Cochrane review of vitamin B12 and cognitive function is being prepared. Objectives: To examine the effects of folic acid supplementation, with or without vitamin B12, on elderly healthy and demented people, in preventing cognitive impairment or retarding its progress. Search strategy: Trials were identified from a search of the Cochrane Dementia and Cognitive Improvement Specialized Register Group on 9 April 2003 using the terms: folic acid, folate, vitamin B9, leucovorin, methyltetrahydrofolate, vitamin B12, cobalamin, cyanocobalamin, dementia, cognitive function, cognitive impairment, Alzheimer's disease, vascular dementia, mixed dementia and controlled trials. MEDLINE and EMBASE (both all years) were searched for additional trials on healthy people. Selection criteria: All double-blind placebo-controlled randomized trials, in which supplements of folic acid with or without vitamin B12 were compared with placebo for elderly healthy people or people with any type of dementia or cognitive impairment. Data collection and analysis: The reviewers independently applied the selection criteria and assessed study quality. One reviewer extracted and analysed the data. In comparing intervention with placebo, weighted mean differences, and standardized mean difference or odds ratios were estimated. Main results: Four randomized controlled trials fulfilled the inclusion criteria for this review. One trial (Bryan 2002) enrolled healthy women, and three (Fioravanti 1997; Sommer 1998; VITAL 2003) recruited people with mild to moderate cognitive impairment or dementia with or without diagnosed folate deficiency. Fioravanti 1997 enrolled people with mild to moderate cognitive impairment or dementia as judged by scores on the Mini-Mental State Examination (MMSE) and Global Deterioration Scale and with serum folate level<3ng/l. One trial (VITAL 2003) studied the effects of a combination of vitamin B12 and folic acid on patients with mild to moderate cognitive impairment due to Alzheimer's disease or mixed dementia. The analysis from the included trials found no benefit from folic acid with or without vitamin B12 in comparison with placebo on any measures of cognition and mood for healthy or cognitively impaired or demented people: Folic acid effect and healthy participants: there was no benefit from of oral 750 mcg folic acid per day for five weeks compared with placebo on measures of cognition and mood of 19 healthy women aged 65 to 92. Folic acid effect and people with mild to moderate cognitive decline or dementia: there were no statistically significant results in favour of folic acid with or without vitamin B12 on any measures of cognitive function. Scores on the Mini-Mental State Examination (MMSE) revealed no statistically significant benefit from 2 mg per day folic acid plus 1mg vitamin B12 for 12 weeks when compared with placebo (WMD 0.39, 95% CI -0.43 to 1.21, P=0.35). Cognitive scores on the Alzheimer's Disease Scale (ADAS-Cog) showed no statistically significant benefit from 2 mg /day folic acid plus 1 mg /day vitamin B12 for 12 weeks compared with placebo (WMD 0.41, 95% -1.25 to 2.07, P=4.63). The Bristol Activities of Daily Living Scale (BADL) revealed no benefit from 2mg per day of folic acid plus 1 mg vitamin B12 for 12 weeks in comparison with placebo (WMD -0.57, 95%CI -1.95 to 0.81, P=0.42). None of the sub tests of the Randt Memory Test (RMT) showed statistically significant benefit from 15 mg of folic acid orally per day for 9 weeks when compared with placebo. One trial (Sommer 1998) reported a significant decline compared with placebo in two cognitive function tasks in demented patients who had received high doses of folic acid (10 mg /day) for unspecified periods. One trial (VITAL 2003) showed that 2 mg folic acid plus 1 mg vitamin B12 daily for 12 weeks significantly lowered serum homocysteine concentrations (P <0.0001). Reviewer's conclusions: There was no beneficial effect of 750 mcg of folic acid per day on measures of cognition or mood in older healthy women. In patients with mild to moderate cognitive decline and different forms of dementia there was no benefit from folic acid on measures of cognition or mood. Folic acid plus vitamin B12 was effective in reducing the serum homocysteine concentrations. Folic acid was well tolerated and no adverse effects were reported. More studies are needed.

251 citations


Journal ArticleDOI
TL;DR: It is suggested that platinum-based adjuvant chemotherapy improves survival and delays recurrence in patients with early-stage ovarian cancer.
Abstract: The question of whether platinum-based adjuvant chemotherapy can improve outcomes in patients with early-stage epithelial ovarian cancer is an important one. We carried out a multicenter, open randomized trial to determine whether adjuvant chemotherapy would improve overall survival and prolong recurrence-free survival in women with early-stage epithelial ovarian cancer.

248 citations


Journal ArticleDOI
TL;DR: This study aims to determine the accuracy of transvaginal ultrasonography, sonohysterography and diagnostic hysteroscopy for the investigation of abnormal uterine bleeding in premenopausal women.
Abstract: Background. To determine the accuracy of transvaginal ultrasonography, sonohysterography and diagnostic hysteroscopy for the investigation of abnormal uterine bleeding in premenopausal women. Desig...

206 citations


Journal ArticleDOI
TL;DR: Evidence of any efficacy of vitamin B12 in improving the cognitive function of people with dementia and low serum B12 levels is insufficient and a review is needed of trials assessing effects of vitamins B12 supplementation on cognitive function in later life.
Abstract: Background An association between neuropsychiatric disorders and vitamin B12 deficiency has been recognized since 1849 when pernicious anaemia was first described. It has been suggested that deficiency of vitamin B12 might contribute to age-associated cognitive impairment. Low serum vitamin B12 concentrations are found in more than 10% of older people. A high prevalence of low serum vitamin B12 levels, and other indicators of vitamin B12 deficiency have been reported among people with Alzheimer's disease. A review is needed of trials assessing effects of vitamin B12 supplementation on cognitive function in later life. Objectives To examine the effect of B12 supplementation on cognitive function of demented and elderly healthy people in terms of preventing the onset or progression of cognitive impairment or dementia. Search methods The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 24 January 2006 using the terms B12, "B 12", B-12, B-complex, "B complex". In addition MEDLINE 1966 to 2006/01-week 3 and EMBASE 1980-2005/12 were searched to pick up studies with healthy volunteers. Selection criteria All randomized double-blind trials in which vitamin B12 at any dose was compared with placebo. Data collection and analysis Both reviewers applied the selection criteria to assess the quality of the studies. One reviewer (RM) collated and analysed the data. For each outcome measure data were sought on every patient randomized. Main results Three trials were included (De La Fourniere 1997; Hvas 2004; Seal 2002). One trial (Hvas 2004) reported follow-up results at 3 months after randomization, 2 months after treatment was completed; the data from this study were not combined with others. People with dementia and low serum vitamin B12 levels were recruited for the studies. The results showed no statistically significant evidence of a treatment effect of vitamin B12 supplementation compared with placebo, on cognitive function. Authors' conclusions Evidence of any efficacy of vitamin B12 in improving the cognitive function of people with dementia and low serum B12 levels is insufficient. The included trials (De La Fourniere 1997; Hvas 2004; Seal 2002) were restricted to a small number of patients with Alzheimer's disease and other types of cognitive impairment. No trials involving people without dementia or using other definitions of vitamin B12 deficiency were found.

Journal ArticleDOI
TL;DR: This research presents a novel and exciting new approach to pharmacological therapy in acute variceal bleeding by utilizing a novel “drug-like” approach called “coagulation-by-drugs”.
Abstract: Background: Controversy exists surrounding pharmacological therapy in acute variceal bleeding. Methods: To determine the efficacy and safety of terlipressin. Methods: Randomized trials were identified and duplicate, independent, review identified 20 randomized trials involving 1609 patients that compared terlipressin with placebo, balloon tamponade, endoscopic treatment, octreotide, somatostatin or vasopressin for treatment of acute oesophageal variceal haemorrhage. Results: Meta-analysis showed that compared to placebo, terlipressin reduced mortality (relative risk 0.66, 95% CI 0.49-0.88), failure of haemostasis (relative risk 0.63, 95% CI 0.45-0.89) and the number of emergency procedures per patient required for uncontrolled bleeding or rebleeding (relative risk 0.72, 95% CI 0.55-0.93). When used as an adjuvant to endoscopic sclerotherapy, terlipressin reduced failure of haemostasis (relative risk 0.75, 95% CI 0.58-0.96), and had an effect on reducing mortality that approached statistical significance (relative risk 0.74, 95% CI 0.53-1.04). No significant difference was demonstrated between terlipressin and endoscopic sclerotherapy, balloon tamponade, somatostatin or vasopressin. Haemostasis was achieved more frequently with octreotide compared to terlipressin (relative risk 1.62, 95% CI 1.05-2.50), but this result was based on unblinded studies. Adverse events were similar between terlipressin and the other comparison groups except for vasopressin, which caused more withdrawals due to adverse events. Conclusions: Terlipressin is a safe and effective treatment for acute oesophageal variceal bleeding, with or without adjuvant endoscopic sclerotherapy. Terlipressin appears to reduce mortality in acute oesophageal variceal bleeding compared to placebo, and is the only pharmacological agent shown to do so. Future studies will be required to detect potential mortality differences between terlipressin and other therapeutic approaches.

Journal ArticleDOI
16 May 2003-Vaccine
TL;DR: The adverse event profile of acellular vaccines was similar to that of placebo and considerably better than that of whole-cell vaccines, making interpretation of direct comparisons unreliable.

Reference EntryDOI
TL;DR: NSAIDs are an effective treatment for dysmenorrhoea, though women using them need to be aware of the significant risk of adverse effects, and there is insufficient evidence to determine which (if any) individual NSAID is the most safe and effective for the treatment of dysmena.
Abstract: Background Dysmenorrhoea is a common gynaecological complaint consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary dysmenorrhoea Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs which act by blocking prostaglandin production Objectives The purpose of this review is to compare all nonsteroidal anti-inflammatory drugs used in the treatment of primary dysmenorrhoea with placebo, with paracetamol and with each other to evaluate their effectiveness and safety Search strategy We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (11 April 2003), Cochrane Central Register of Controlled Trials (1st quarter 2003), MEDLINE (1966-April 2003), and EMBASE (1980 - Week 15 2003) Attempts were also made to identify trials from the National Research Register and the Clinical Trials Register Citation lists of relevant publications, review articles, abstracts of major scientific meetings and included studies were also searched Selection criteria All randomised controlled comparisons of NSAID therapies versus placebo, versus other NSAIDs or versus paracetamol when used to treat primary dysmenorrhoea Data collection and analysis Two reviewers independently assessed trials for quality and extracted data, calculating odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes Crossover trial data were presented in additional tables and other data were summarised descriptively Main results In women with dysmenorrhoea, NSAIDs were found significantly more effective for pain relief than placebo (OR 791, 95% CI 565 to 1109), though overall adverse effects were also significantly more common (OR 152 95% CI 109 to 212) When NSAIDs were compared with each other or with paracetamol, there was little evidence of the superiority of any individual NSAID with regard to either efficacy or safety However the available evidence had little power to detect such differences, as most individual comparisons were based on very few small trials, most of which were unsuitable for meta-analysis Authors' conclusions NSAIDs are an effective treatment for dysmenorrhoea, though women using them need to be aware of the significant risk of adverse effects There is insufficient evidence to determine which (if any) individual NSAID is the most safe and effective for the treatment of dysmenorrhoea

Patent
31 Oct 2003
TL;DR: In this paper, a taxonomy of pre-computed information stored in auxiliary structures to speed up processing of expensive queries on hierarchical documents such as XML documents being queried using XPath is presented.
Abstract: A method for using pre-computed information stored in auxiliary structures to speed up processing of expensive queries on hierarchical documents such as XML documents being queried using XPath. The invention defines a taxonomy of such structures such as indexes and materialized views for storing pre-computed XPath results (PXRs), determines what portion of the query can be evaluated by the structures, and computes the compensation for the results generated by the structures. The invention detects all structures applicable to the query and rewrites the query to use such structures, speeding up the performance of the queries. The invention identifies the matching structures by detecting containment mappings between XPath expressions in the query and the structure. The invention also includes a new representation for XPath expressions that is rich enough to express all features of XPath.

Journal ArticleDOI
TL;DR: The results suggest that parenting programmes can be effective in improving a range of psychosocial and developmental outcomes for teenage mothers and their children.


Journal Article
TL;DR: Reliable data are rare regarding the accuracy of physical diagnostic tests for ACL ruptures, especially in a primary care setting, and history taking and physical examination, albeit of limited use, should be considered with individual patient demands to provide the basis for further evaluation.
Abstract: Objective This systematic review summarizes the evidence on the accuracy of tests for assessing ACL ruptures of the knee.

Reference EntryDOI
TL;DR: The provision of recordings or summaries of key consultations to people with cancer or their families may benefit most adults with cancer, and practitioners should consider offering people tape recordings or written summary of their consultations.
Abstract: BACKGROUND: Many people find it difficult to remember information provided during medical consultations. One way of improving this may be to provide a record of the conversation. OBJECTIVES: This review examined the effects of providing recordings or summaries of their consultations to people with cancer and their families. SEARCH STRATEGY: We searched the following sources: The Cochrane Library (issue 4 2002); MEDLINE (1966 to January week 1 2003); CINAHL (1982 to December week 4 2002); Dissertation Abstracts (1861 to week 2 2003); EMBASE (1985 to week 2 2003); PsycINFO (1967 to January week 2 2003); AMED (1985 to December 2002); and Sociological Abstracts (1998 to week 2 2003). For the initial (1999) publication of this review we also searched the following databases: Sociofile; Cancerlit; IAC Health & Wellness; JICST; Pascal; ERIC; ASSIA; Linguistics and Language Behavior Abstracts; Mental Health Abstracts; CAB Health; DHSS-Data; MANTIS. SELECTION CRITERIA: Randomised and non-randomised controlled trials that evaluate the effects of providing recordings (e.g. audiotapes) or summaries (e.g. letter with reminders of key points) of consultations to people with cancer or their families. Two reviewers assessed studies for inclusion. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and checked by another reviewer. The quality of studies was assessed on six criteria. MAIN RESULTS: Twelve studies satisfied the selection criteria. All involved adult participants. The studies did not all measure similar outcomes. In seven studies, between 83% and 96% of participants found recordings or summaries of their consultations valuable. Five out of nine studies reported better recall of information for those receiving recordings or summaries. Four out of seven studies found that participants provided with a recording or summary were more satisfied with the information received. No studies (out of seven) found any statistically significant effect on anxiety or depression. One study evaluated the effects on quality of life, but found no main effects. No study evaluated the effects on survival. REVIEWER'S CONCLUSIONS: The provision of recordings or summaries of key consultations may benefit most adults with cancer. Although more research is needed to improve our understanding of these interventions, most patients find them very useful. Practitioners should consider offering people tape recordings or written summaries of their consultations

Journal ArticleDOI
TL;DR: The number of studies in a typical Cochrane review is used to provide an estimate of the number of Cochrane reviews that are needed to cover all trials currently in the Cochrane Central Register of Controlled Trials (CENTRAL).
Abstract: Clinicians are faced with the challenge of keeping abreast of the rapidly growing clinical literature. One method that can help clinicians meet this challenge is the provision of synthesised evidence by such groups as the Cochrane Collaboration. The Cochrane Library contains the full text of Cochrane reviews, which bring together information on controlled studies (mostly randomised controlled trials) in a standard format. The first 1000 reviews were prepared by early 2001, and there are now more than 1600 available.1 The task of synthesising the clinical literature is a huge undertaking, and in this editorial we will use the number of studies in a typical Cochrane review to provide an estimate of the number of Cochrane reviews that are needed to cover all trials currently in the Cochrane Central Register of Controlled Trials (CENTRAL).2–3 CENTRAL is the main source used by Cochrane reviewers to locate studies. It contains citations to more than 300 000 reports of studies, which may be eligible for inclusion in Cochrane reviews. CENTRAL is reference-based rather than study-based, and therefore multiple references may be included for a single trial. We examined 1000 reviews from the Cochrane Database of Systematic Reviews in Issue 1, 2001, of the Cochrane Library to determine the average number of studies, and references to the studies, included in a typical Cochrane review. Comparing this with an estimate for the number of relevant references in CENTRAL, it is possible to predict how many more Cochrane reviews are needed to cover the healthcare research already in CENTRAL. Of the 1000 reviews, 11 had been replaced by notices of withdrawal, leaving 989 complete reviews. The included studies in these reviews were hand counted by 1 author …

Reference EntryDOI
TL;DR: There is no current evidence supporting the clinical use of antidepressants in the treatment of cocaine dependence, and clinicians may consider adding psychotherapeutic supportive measures aiming to keep patients in treatment.
Abstract: Background Cocaine dependence is a common and serious condition, which has become nowadays a substantial public health problem. The past decade has witnessed a sustained search for an effective pharmacotherapeutic agent for the treatment of cocaine dependence. While administration of cocaine acutely increases intercellular dopamine, serotonin, and norepinephrine levels by blocking their presynaptic reuptake, chronic cocaine abuse leads to down-regulation of monoamine systems. Post-cocaine use depression and cocaine craving may be linked to this down-regulation. Antidepressant pharmacotherapy, by augmenting monoamine levels, may alleviate cocaine abstinence symptomatology, as well as relieving dysphoria and associated craving by general antidepressant action. Objectives To conduct a systematic review of all RCTs on the use of antidepressants for treating cocaine dependence. Search strategy We searched the Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (from 1966 - 2000), EMBASE (from 1980 - 2000), LILACS (from 1982 - 2000), PsycLIT (from 1974 - 2000), Biological Abstracts (1982 to 2000). Other searches:reference searching; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. Selection criteria The inclusion criteria for all randomised controlled trials were that they should focus on the use of antidepressants on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. Data collection and analysis The reviewers extracted the data independently and Relative Risks, weighted mean difference and number needed to treat were estimated. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. Main results 18 studies were included in the review, with 1177 people randomised. Positive urine sample for cocaine metabolites was the main efficacy outcome, with no significant results obtained regardless the type of antidepressant. Compared to other drugs, desipramine performed better but showing just a non significant trend with heterogeneity present as revealed by the chi-square test (8.6, df=3; p=0.04). One single trial showed imipramine performed better than placebo in terms of clinical response according to patient's self-report. A similar rate of patients remaining in treatment was found for both patients taking desipramine or placebo. Results from one single trial suggest fluoxetine patients on SSRIs are less likely to dropout. Similar results were obtained for trials where patients had additional diagnosis of opioid dependence and/or were in methadone maintenance treatment. Reviewer's conclusions There is no current evidence supporting the clinical use of antidepressants in the treatment of cocaine dependence. Given the high rate of dropouts in this population, clinicians may consider adding psychotherapeutic supportive measures aiming to keep patients in treatment.

Reference EntryDOI
TL;DR: The evidence is inadequate to decide whether azathioprine, interferon beta or any other immunosuppressive drug or interferons is beneficial in chronic inflammatory demyelinating polyradiculoneuropathy.
Abstract: Background Chronic inflammatory demyelinating polyradiculoneuropathy is a disease causing progressive or relapsing and remitting weakness and numbness. It is probably due to an autoimmune inflammatory process. Immunosuppressive or immunomodulatory drugs would be expected to be beneficial. Objectives We aimed to review systematically the evidence from randomised trials concerning cytotoxic drugs and interferons for chronic inflammatory demyelinating polyradiculoneuropathy. Search strategy We searched the Cochrane Neuromuscular Disease Group trials register (searched December 2001), MEDLINE (searched January 1977 to December 2001), EMBASE (January 1980 to December 2001), CINAHL (searched January 1982 to December 2001) and LILACS (searched January 1982 to December 2001). We contacted the authors of the trials identified and other disease experts seeking other published and unpublished trials. Selection criteria We sought randomised and quasi-randomised trials of all immunosuppressive agents such as azathioprine, cyclophosphamide, methotrexate, cyclosporin A, mycophenolate mofetil, and rituximab and all immunomodulatory agents such as alpha interferon and beta interferon in participants fulfilling standard diagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy. Data collection and analysis Two of us independently selected the trials which met our criteria, judged their methodological quality and extracted the data onto specially designed forms. We wanted to measure the change in disability after one year as our primary outcome measure. Main results We found one parallel group open trial of azathioprine for nine months involving 27 participants and another of interferon beta involving 10 participants in a double blind crossover trial with each treatment period lasting 12 weeks. Neither trial provided our primary outcome measure and neither showed a significant beneficial effect on any of the outcome measures selected by the authors or ourselves in the protocol for this review. Reviewer's conclusions The evidence is inadequate to decide whether azathioprine, interferon beta or any other immunosuppressive drug or interferon is beneficial in chronic inflammatory demyelinating polyradiculoneuropathy.

Reference EntryDOI
TL;DR: Current evidence does not support the clinical use of dopamine agonists in the treatment of cocaine dependence, and clinicians may consider adding psychotherapeutic supportive measures aiming to keep patients in treatment.
Abstract: Background Cocaine is a major drug of abuse. Cocaine dependence is a common and serious condition, which has become nowadays a substantial public health problem. There is a wide and well documented range of consequences associated to chronic use of this drug, such as medical, psychological and social problems, including the spread of infectious diseases (e.g. AIDS, hepatitis and tuberculosis), crime, violence and neonatal drug exposure. Therapeutic management of the cocaine addicts includes an initial period of abstinence from the drug. During this phase the subjects may experience, besides the intense craving for cocaine, symptoms such as depression, fatigue, irritability, anorexia, and sleep disturbances. It was demonstrated that the acute use of cocaine may enhance dopamine transmission and chronically it decreases dopamine concentrations in the brain. Pharmacological treatment that affects dopamine could theoretically reduce these symptoms and contribute to a more successful therapeutic approach. Objectives To evaluate the efficacy and acceptability of dopamine agonists for treating cocaine dependence. Search strategy We searched: The Cochrane Controlled Trials Register (Cochrane Library, issue 4, 2000), MEDLINE (from 1966 - 2000), EMBASE (from 1980 - 2000), LILACS (from 1982 - 2000), PsycLIT (from 1974 - 2000), Biological Abstracts (1982 to 2000). Reference searching; personal communication; conference abstracts; unpublished trials from pharmaceutical industry; book chapters on treatment of cocaine dependence. Selection criteria The inclusion criteria for all randomised controlled trials were that they should focus on the use of dopamine agonists on the treatment of cocaine dependence. Trials including patients with additional diagnosis such as opiate dependence were also eligible. Data collection and analysis The reviewers extracted the data independently and Relative Risks, weighted mean difference and number needed to treat were estimated. The reviewers assumed that people who died or dropped out had no improvement and tested the sensitivity of the final results to this assumption. Main results Twelve studies were included, with 587 participants randomised. Amantadine and Bromocriptine were compared to placebo in most of trials. In two studies amantadine was directly compared to bromocriptine, while amantadine was compared to desipramine, an antidepressant in three. The main efficacy outcome presented was positive urine sample for cocaine metabolites, with no significant differences between interventions. When retention in treatment was assessed as an acceptability measure, it was found a similar rate of patients remaining in treatment in both placebo and active drugs. There were no significant differences in trials where participants had primary cocaine dependence or had additional diagnosis of opioid dependence and/or were in methadone maintenance treatment. Reviewer's conclusions Current evidence does not support the clinical use of dopamine agonists in the treatment of cocaine dependence. Given the high rate of dropouts in this population, clinicians may consider adding psychotherapeutic supportive measures aiming to keep patients in treatment.

Reference EntryDOI
TL;DR: Assessment of the efficacy and acceptability of heroin maintenance versus methadone or other substitution treatments for opioid dependence, in retaining patients in treatment; reducing the use of illicit substances and improving health and social functioning and no definitive conclusions are possible.
Abstract: BACKGROUND Dependent heroin users are characterised by the persistence of use in spite of the difficulties they experience with health, law, social achievements and personal relationships. The present review will consider maintenance treatment in which the patients enter programs of pharmacological administration tailored to achieve patient stabilisation. Many medications have been used for this purpose such as: Methadone, Buprenorphine and LAAM. The present review will focus on maintenance treatment through the prescription of heroin. OBJECTIVES To assess the efficacy and acceptability of heroin maintenance versus methadone or other substitution treatments for opioid dependence, in retaining patients in treatment; reducing the use of illicit substances and improving health and social functioning. SEARCH STRATEGY The Cochrane Central Register of Trials (CENTRAL) issue 4, 2002; MEDLINE (on Silver Platter) 1966-2002; EMBASE (on OVID) 1980-2000 and CINAHL till 2000 were searched. There was no language or publication year restrictions. Many researchers were contacted for information. SELECTION CRITERIA Randomised controlled trials of heroin (alone or combined with methadone) maintenance treatment compared with any other pharmacological treatments. DATA COLLECTION AND ANALYSIS The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked. Studies were not pooled together because of heterogeneity. MAIN RESULTS 2400 references were obtained and 20 studies were eligible, 4 met the inclusion criteria for a total of 577 patients. The studies included could not be analysed cumulatively because of heterogeneity of interventions and outcomes considered. Two studies compared injected heroin to oral methadone for 1 year (270 patients) but considered different outcomes; one study compared injected heroin and methadone to oral methadone for 6 months (51 patients); and one compared inhaled heroin and methadone to oral methadone for 1 year (235 patients). Retention in treatment: in two studies there was no statistical difference between groups; one study (N=90) had a RR=2.49 (95% CI 1.51-4.10) in favour of heroin; one study (N=235) had a RR 0.79 (95%CI 0.68-0.90) in favour of methadone. Relapse to illegal heroin use, based on self report: in one study the proportion of people still using heroin were 64% in the heroin group, 59% methadone group; in the other study the RR was 0.33 (95%CI 0.15-0.72) in favour of heroin. The remaining studies did not provide the data. Criminal offence: one of the two studies which provided details about this showed the potential of heroin prescription in reducing the risk of being charged RR 0.32 (95% CI 0.14-0.78). Social functioning: the two studies reporting this outcome did not show statistical difference between intervention groups. The two most recent studies considered criminal offence and social functioning as part of a multidomain outcome measure and showed higher improvement among those treated with heroin plus methadone over those on methadone only. REVIEWER'S CONCLUSIONS No definitive conclusions about the overall effectiveness of heroin prescription is possible because of non-comparability of the experimental studies available to be included in this review. Results favouring heroin treatment come from studies conducted in countries where the treatment system is comprehensive and easy accessible Methadone Maintenance Treatment at effective dosages is available. In those studies heroin prescription was addressed to patients who had failed previous methadone treatments.

Journal ArticleDOI
30 Oct 2003-BMJ
TL;DR: The future of non-commercial randomised controlled trials in the United Kingdom has been threatened by the discontinuation or demise of national and regional NHS research and development programmes and support also seems to be declining from the Medical Research Council and the medical research charities.
Abstract: Objectives To describe the characteristics of randomised controlled trials supported by the main non-commercial sources of funding in the United Kingdom between 1980 and 2002. Design Descriptive survey. Setting Randomised controlled trials funded by the Medical Research Council, NHS research and development programme, Department of Health, Chief Scientist Office in Scotland, and medical research charities. Participants 1464 randomised controlled trials supported by the main non-commercial sources of funding. Results Support for randomised controlled trials by the main sources of non-commercial funding in the United Kingdom has fallen in recent years, without any concomitant increase in the sample sizes of these studies. Drug trials in a limited range of health problems have dominated among the studies supported by the Medical Research Council and medical research charities. Until recently, the NHS research and development programme supported randomised controlled trials of various healthcare interventions, in a wide range of health problems, but between 1999 and 2002 many of the subprogrammes that had commissioned trials were discontinued. Conclusions The future of non-commercial randomised controlled trials in the United Kingdom has been threatened by the discontinuation or demise of national and regional NHS research and development programmes. Support also seems to be declining from the Medical Research Council and the medical research charities. It is unclear what the future holds for randomised controlled trials that address issues of no interest to industry but are of great importance to patients and practitioners.

Journal ArticleDOI
01 Mar 2003-BMJ
TL;DR: The impossibility of proving no effect or no difference should be distinguished from the concept used for equivalence trials, where bounds are set on the differences that are deemed practically important.
Abstract: It is never correct to claim that treatments have no effect or that there is no difference in the effects of treatments. It is impossible to prove a negative or that two treatments have the same effect. There will always be some uncertainty surrounding estimates of treatment effects, and a small difference can never be excluded.1 Claims of no effect or no difference may mean that patients continue to be denied or exposed to interventions with important effects, either beneficial or harmful. They may also suggest that further research is unnecessary, so delaying satisfactory estimates of treatment effects. The impossibility of proving no effect or no difference should be distinguished from the concept used for equivalence trials, where bounds are set on the differences that are deemed practically important. An analysis of 45 reports of trials purporting to test equivalence …

Journal ArticleDOI
02 Jun 2003-Vaccine
TL;DR: Despite poor design and reporting of trials, convincing evidence of the effectiveness and safety of inactivated HAV vaccines is found.

Journal ArticleDOI
TL;DR: In this paper, the authors fed five diets (eight/group) for four weeks to Hamsters and found no significant differences in growth, or liver and adipose weights, but increased the total cholesterol (TC) by 10%.

Patent
Robert Bradshaw1, Kevin Cochrane1, Jack Jia1, Britt Park1, Meili Zhong1 
10 Feb 2003
TL;DR: In this article, a system and method for creating component to save storage space, and to efficiently organize and maintain content is presented, where a system is provided that is configured to manage the componentization (802) of content within entities that share common content.
Abstract: A system and method is provided for creating component to save storage space, and to efficiently organize and maintain content. In one embodiment, a system is provided that is configured to manage the componentization (802) of content within entities that share common content. The system includes a content control (118) module configured to manage the editing (236) of content and their state, such as whether and when they were modified (606) or mutated (610). Alternatively, the system may include a repository (700) configured to manage the indexing (702) and searching of component (704).

Journal ArticleDOI
TL;DR: There is a clear lack of evidence to support the use of azathioprine in the treatment of chronic asthma as a steroid sparing-agent, and large, long-term studies with pre-defined steroid reducing protocols are required before recommendations for clinical practice can be made.
Abstract: Background For the majority of chronic asthmatics, symptoms are best controlled by using inhaled steroids. However, for a small group of asthmatics, symptoms can only be controlled by high doses of oral steroids.Continuous use of oral steroid is associated with severe side-effects, but it has been suggested that azathioprine, an immunosuppressive anti-metabolite, often used to reduce the immune response in chronic active hepatitis and severe rheumatoid arthritis, could be useful as an oral steroid sparing agent. There is a need to systematically evaluate the evidence regarding its use to reduce or eliminate oral corticosteroid usage. Objectives The objective of this review is to assess the efficacy of adding azathioprine in patients with stable asthma who are dependent on oral corticosteroids with the intention of eventually minimizing or eliminating the use of these steroids. Search methods Searches of the Cochrane Airways Group Specialised Register were undertaken with predefined search terms. Searches were current asof August 2010. Selection criteria Only studies with a randomised placebo-controlled design met the inclusion criteria for the review. Data collection and analysis Two authors independently assessed studies for suitability for inclusion in the review. Data were extracted and entered into Review Manager. Main results Two small trials recruiting 23 participants met the inclusion criteria for the review. Participants may have been suffering from comorbid lung disease. No data on oral steroid consumption were reported. No significant differences were observed in the studies for FEV1, FVC, PaO2 and symptoms. One study reported a statistically significant difference in SGaw, but the clinical importance of this is ncertain. Due to concerns over the small sample sizes and methodological shortcomings in terms of inadequate washout in one study, and methods used in outcome assessment for both studies, the findings of the studies are not generalisable to the issue of steroid tapering. An update search conducted in August 2010 did not identify any new studies for consideration in the review. Authors’ conclusions Currently there is a clear lack of evidence to support the use of a zathioprine in the treatment of chronic asthma as a steroid sparing-agent. Large, long-term studies with pre-defined steroid reducing protocols are required before recommendations for clinical practice can be made.