Showing papers by "Cochrane Collaboration published in 2005"

Meta-analysis of individual patient data from randomized trials: a review of methods used in practice.

Abstract: Background Meta-analyses based on individual patient data (IPD) are regarded as the gold standard for systematic reviews. However, the methods used for analysing and presenting results from IPD met...

Criteria for the systematic review of health promotion and public health interventions.

Abstract: Systematic reviews of public health interventions are fraught with challenges. Complexity is inherent; this may be due to multi-component interventions, diverse study populations, multiple outcomes measured, mixed study designs utilized and the effect of context on intervention design, implementation and effectiveness. For policy makers and practitioners to use systematic reviews to implement effective public health programmes, systematic reviews must include this information, which seeks to answer the questions posed by decision makers, including recipients of programmes. This necessitates expanding the traditional evaluation of evidence to incorporate the assessment of theory, integrity of interventions, context and sustainability of the interventions and outcomes. Unfortunately however, the critical information required for judging both the quality of a public health intervention and whether or not an intervention is worthwhile or replicable is missing from most public health intervention studies. When the raw material is not available in primary studies the systematic review process becomes even more challenging. Systematic reviews, which highlight these critical gaps, may act to encourage better reporting in primary studies. This paper provides recommendations to reviewers on the issues to address within a public health systematic review and, indirectly, provides advice to researchers on the reporting requirements of primary studies for the production of high quality systematic reviews.

Need for expertise based randomised controlled trials.

Abstract: Surgical procedures are less likely to be rigorously evidence based than drug treatments because of difficulties with randomisation. Expertise based trials could be the way forward Although conventional randomised controlled trials are widely recognised as the most reliable method to evaluate pharmacological interventions,1 2 scepticism about their role in nonpharmacological interventions (such as surgery) remains.3–6 Conventional randomised controlled trials typically randomise participants to one of two intervenions (A or B) and individual clinicians give intervention A to some participants and B to others. An alternative trial design, the expertise based randomised controlled trial, randomises participants to clinicians with expertise in intervention A or clinicians with expertise in intervention B, and the clinicians perform only the procedure they are expert in. We present evidence to support our argument that increased use of the expertise based design will enhance the validity, applicability, feasibility, and ethical integrity of randomised controlled trials in surgery, as well as in other areas. We focus on established surgical interventions rather than new surgical procedures in which clinicians have not established expertise. Investigators have used the expertise based design when conventional randomised controlled trials were impossible because different specialty groups provided the interventions under evaluation—for example, percutaneous transluminal coronary angioplasty versus coronary artery bypass graft surgery.7–9 In 1980, Van der Linden suggested randomising participants to clinicians committed to performing different interventions in an area in which a conventional randomised controlled trial was possible.10 Since that time, however, the expertise based design has been little used, even in areas where it has high potential (such as, surgery, physiotherapy, and chiropractic). ### Differential expertise between procedures Because it takes training and experience to develop expertise in surgical interventions, individual surgeons tend to solely or primarily use a single surgical approach to treat a specific problem.10 11 …

Manual versus powered toothbrushing for oral health

Abstract: BACKGROUND: Removing dental plaque may play a key role maintaining oral health. There is conflicting evidence for the relative merits of manual and powered toothbrushing in achieving this. OBJECTIVES: To compare manual and powered toothbrushes in relation to the removal of plaque, the health of the gingivae, staining and calculus, dependability, adverse effects and cost. SEARCH STRATEGY: We searched the Cochrane Oral Health Group Trials Register (to 17/06/2004) and Central Register of Controlled Trials (The Cochrane Library Issue 2, 2004); MEDLINE (January 1966 to week 2 June 2004); EMBASE (January 1980 to week 2 2004) and CINAHL (January 1982 to week 2 June 2004). Manufacturers were contacted for additional data. SELECTION CRITERIA: Trials were selected for the following criteria: design-random allocation of participants; participants - general public with uncompromised manual dexterity; intervention - unsupervised manual and powered toothbrushing for at least 4 weeks. Primary outcomes were the change in plaque and gingivitis over that period. DATA COLLECTION AND ANALYSIS: Six authors independently extracted information. The effect measure for each meta-analysis was the standardised mean difference (SMD) with 95% confidence intervals (CI) using random-effects models. Potential sources of heterogeneity were examined, along with sensitivity analyses for quality and publication bias. For discussion purposes SMD was translated into percentage change. MAIN RESULTS: Forty-two trials, involving 3855 participants, provided data.Brushes with a rotation oscillation action removed plaque and reduced gingivitis more effectively than manual brushes in the short term and reduced gingivitis scores in studies over 3 months. For plaque at 1 to 3 months the SMD was -0.43 (95% CI: -0.72 to -0.14), for gingivitis SMD -0.62 (95% CI: -0.90 to -0.34) representing an 11% difference on the Quigley Hein plaque index and a 6% reduction on the Loe and Silness gingival index. At over 3 months the SMD for plaque was -1.29 (95% CI: -2.67 to 0.08) and for gingivitis was -0.51 (-0.76 to -0.25) representing a 17% reduction on the Ainamo Bay bleeding on probing index. There was heterogeneity between the trials for the short-term follow up. Sensitivity analyses revealed the results to be robust when selecting trials of high quality. There was no evidence of any publication bias.No other powered designs were as consistently superior to manual toothbrushes.Cost, reliability and side effects were inconsistently reported. Any reported side effects were localised and temporary. AUTHORS' CONCLUSIONS: Powered toothbrushes with a rotation oscillation action reduce plaque and gingivitis more than manual toothbrushing.Observation of methodological guidelines and greater standardisation of design would benefit both future trials and meta-analyses.

Assessment of methodological quality of primary studies by systematic reviews: results of the metaquality cross sectional study.

Abstract: Objectives To describe how the methodological quality of primary studies is assessed in systematic reviews and whether the quality assessment is taken into account in the interpretation of results. Data sources Cochrane systematic reviews and systematic reviews in paper based journals. Study selection 965 systematic reviews (809 Cochrane reviews and 156 paper based reviews) published between 1995 and 2002. Data synthesis The methodological quality of primary studies was assessed in 854 of the 965 systematic reviews (88.5%). This occurred more often in Cochrane reviews than in paper based reviews (93.9% v 60.3%, P < 0.0001). Overall, only 496 (51.4%) used the quality assessment in the analysis and interpretation of the results or in their discussion, with no significant differences between Cochrane reviews and paper based reviews (52% v 49%, P = 0.58). The tools and methods used for quality assessment varied widely. Conclusions Cochrane reviews fared better than systematic reviews published in paper based journals in terms of assessment of methodological quality of primary studies, although they both largely failed to take it into account in the interpretation of results. Methods for assessment of methodological quality by systematic reviews are still in their infancy and there is substantial room for improvement.

HIV and male circumcision—a systematic review with assessment of the quality of studies

Abstract: This Cochrane systematic review assesses the evidence for an interventional effect of male circumcision in preventing acquisition of HIV-1 and HIV-2 by men through heterosexual intercourse. The review includes a comprehensive assessment of the quality of all 37 included observational studies. Studies in high-risk populations consisted of four cohort studies, 12 cross-sectional studies, and three case-control studies; general population studies consisted of one cohort study, 16 cross-sectional studies, and one case-control study. There is evidence of methodological heterogeneity between studies, and statistical heterogeneity was highly significant for both general population cross-sectional studies (chi(2)=132.34; degrees of freedom [df]=15; p<0.00001) and high-risk cross-sectional studies (chi(2)=29.70; df=10; p=0.001). Study quality was very variable and no studies measured the same set of potential confounding variables. Therefore, conducting a meta-analysis was inappropriate. Detailed quality assessment of observational studies can provide a useful visual aid to interpreting findings. Although most studies show an association between male circumcision and prevention of HIV, these results may be limited by confounding, which is unlikely to be adjusted for.

Comparison of descriptions of allocation concealment in trial protocols and the published reports: cohort study

Abstract: Objectives To compare how allocation concealment is described in publications of randomised clinical trials and corresponding protocols, and to estimate how often trial publications with unclear allocation concealment have adequate concealment according to the protocol. Design Cohort study of 102 sets of trial protocols and corresponding publications. Setting Protocols of randomised trials approved by the scientific and ethical committees for Copenhagen and Frederiksberg, 1994 and 1995. Main outcome measures Frequency of adequate, unclear, and inadequate allocation concealment and sequence generation in trial publications compared with protocols, and the proportion of protocols where methods were reported to be adequate but descriptions were unclear in the trial publications. Results 96 of the 102 trials had unclear allocation concealment according to the trial publication. According to the protocols, 15 of these 96 trials had adequate allocation concealment (16%, 95% confidence interval 9% to 24%), 80 had unclear concealment (83%, 74% to 90%), and one had inadequate concealment. When retrospectively defined loose criteria for concealment were applied, 83 of the 102 trial publications had unclear concealment. According to their protocol, 33 of these 83 trials had adequate allocation concealment (40%, 29% to 51%), 49 had unclear concealment (59%, 48% to 70%), and one had inadequate concealment. Conclusions Most randomised clinical trials have unclear allocation concealment on the basis of the trial publication alone. Most of these trials also have unclear allocation concealment according to their protocol.

Selective serotonin re-uptake inhibitors (SSRIs) for preventing migraine and tension-type headaches

Abstract: Background Headache is a common medical problem. In view of recent discoveries about the role of serotonin in pain mechanisms, selective serotonin re-uptake inhibitors (SSRIs) have been evaluated for the prevention of migraine and tension-type headaches (TTH). Objectives To evaluate the efficacy and tolerability of SSRIs for preventing migraine and TTH. Search methods We searched MEDLINE (1966-January 2004), EMBASE (1994-May 2003), the Cochrane Central Register of Controlled Trials (Issue 4, 2003), and reference lists of retrieved articles. Headache Quarterly was hand searched from 1990 to 2003. Selection criteria We included randomised controlled trials comparing SSRIs with any type of control intervention in patients of either sex, over 18 years of age, with migraine or TTH. Data collection and analysis Two authors independently extracted data (headache frequency, index, severity, and duration; use of symptomatic/analgesic medication; days off work; quality of life; mood improvement; cost-effectiveness; and adverse events) and assessed the methodological quality of trials. Main results Thirteen studies utilizing five SSRIs met the inclusion criteria (636 participants). Most of the included studies had methodological and/or reporting shortcomings; follow up rarely extended beyond 3 months. After 2 months SSRIs did not significantly lower headache index scores in patients with migraine when compared to placebo (SMD -0.14; 95% CI -0.57 to 0.30). Patients with chronic TTH treated with an SSRI had a significantly higher analgesic intake of 5 more doses per month when compared to patients treated with a tricyclic antidepressant (WMD 4.98; 95% CI 1.12 to 8.84). Tricyclics also significantly reduced headache duration by 1.26 hours per day (WMD 1.26; 95% CI 0.06 to 2.45) and marginally reduced headache indexes (SMD 0.42; 95% CI 0.00 to 0.85) when compared to SSRIs in patients with chronic TTH. When the data on adverse events were considered without regard to headache diagnostic subgroups, there were no significant differences between SSRIs and placebo for withdrawals due to adverse events (Peto OR 1.02; 95% CI 0.31 to 3.34). For minor adverse events, SSRIs were generally more tolerable than tricyclics (OR 0.34; 95% CI 0.13 to 0.92). However, there were no differences in the number of patients withdrawing due to any reason in the SSRI and tricyclic groups (OR 1.01; 95% CI 0.56 to 1.80). Authors' conclusions Over 2 months of treatment, SSRIs are no more efficacious than placebo in patients with migraine. In patients with chronic TTH, SSRIs are less efficacious than tricyclic antidepressants. In comparison with SSRIs, the burden of adverse events in patients receiving tricyclics was greater. These results are based on short-term trials and may not generalise to longer-term treatment.

Human postural responses to motion of real and virtual visual environments under different support base conditions

Abstract: The role of visual orientation cues for human control of upright stance is still not well understood. We, therefore, investigated stance control during motion of a visual scene as stimulus, varying the stimulus parameters and the contribution from other senses (vestibular and leg proprioceptive cues present or absent). Eight normal subjects and three patients with chronic bilateral loss of vestibular function participated. They stood on a motion platform inside a cabin with an optokinetic pattern on its interior walls. The cabin was sinusoidally rotated in anterior–posterior (a–p) direction with the horizontal rotation axis through the ankle joints (f=0.05–0.4 Hz; Amax=0.25°–4°; vmax=0.08–10°/s). The subjects’ centre of mass (COM) angular position was calculated from optoelectronically measured body sway parameters. The platform was either kept stationary or moved by coupling its position 1:1 to a–p hip position (‘body sway referenced’, BSR, platform condition), by which proprioceptive feedback of ankle joint angle became inactivated. The visual stimulus evoked inphase COM excursions (visual responses) in all subjects. (1) In normal subjects on a stationary platform, the visual responses showed saturation with both increasing velocity and displacement of the visual stimulus. The saturation showed up abruptly when visually evoked COM velocity and displacement reached approximately 0.1°/s and 0.1°, respectively. (2) In normal subjects on a BSR platform (proprioceptive feedback disabled), the visual responses showed similar saturation characteristics, but at clearly higher COM velocity and displacement values (≈1°/s and 1°, respectively). (3) In patients on a stationary platform (no vestibular cues), the visual responses were basically similar to those of the normal subjects, apart from somewhat higher gain values and less-pronounced saturation effects. (4) In patients on a BSR platform (no vestibular and proprioceptive cues, presumably only somatosensory graviceptive and visual cues), the visual responses showed an abnormal increase in gain with increasing stimulus frequency in addition to a displacement saturation. On the normal subjects we performed additional experiments in which we varied the gain of the visual response by using a ‘virtual reality’ visual stimulus or by applying small lateral platform tilts. This did not affect the saturation characteristics of the visual response to a considerable degree. We compared the present results to previous psychophysical findings on motion perception, noting similarities of the saturation characteristics in (1) with leg proprioceptive detection thresholds of approximately 0.1°/s and 0.1° and those in (2) with vestibular detection thresholds of 1°/s and 1°, respectively. From the psychophysical data one might hypothesise that a proprioceptive postural mechanism limits the visually evoked body excursions if these excursions exceed 0.1°/s and 0.1° in condition (1) and that a vestibular mechanism is doing so at 1°/s and 1° in (2). To better understand this, we performed computer simulations using a posture control model with multiple sensory feedbacks. We had recently designed the model to describe postural responses to body pull and platform tilt stimuli. Here, we added a visual input and adjusted its gain to fit the simulated data to the experimental data. The saturation characteristics of the visual responses of the normals were well mimicked by the simulations. They were caused by central thresholds of proprioceptive, vestibular and somatosensory signals in the model, which, however, differed from the psychophysical thresholds. Yet, we demonstrate in a theoretical approach that for condition (1) the model can be made monomodal proprioceptive with the psychophysical 0.1°/s and 0.1° thresholds, and for (2) monomodal vestibular with the psychophysical 1°/s and 1° thresholds, and still shows the corresponding saturation characteristics (whereas our original model covers both conditions without adjustments). The model simulations also predicted the almost normal visual responses of patients on a stationary platform and their clearly abnormal responses on a BSR platform.

Physical activity for secondary prevention of disease. Systematic reviews of randomised clinical trials.

Abstract: Background Physical activity is recommended for secondary prevention of several diseases but it is not always clear how reliable the evidence is. Methods We searched MEDLINE and The Cochrane Library for systematic reviews of randomised clinical trials published 1998-2004. Results We identified 30 eligible systematic reviews and excluded 13 that contained trials covered in larger reviews or were older than other reviews on the same subject. Physical activity decreased all-cause mortality in patients with coronary heart disease, odds ratio 0.73 (95% confidence interval 0.54 to 0.98), increased maximum walking time in patients with intermittent claudication by 6.5 min (4.4 to 8.7), and decreased pain in patients with osteoarthritis of the knee, standardised mean difference 0.34 (0.24 to 0.44). There were positive effects also in heart failure, chronic obstructive lung disease, type 2 diabetes and fibromyalgia, but they need confirmation in high-quality trials. Exercise improved quality of life in several conditions and generally led to improved physical performance. An effect was not shown in stroke, asthma, rheumatoid arthritis, acute or chronic low back pain, chronic fatigue syndrome, depression, cystic fibrosis or HIV/AIDS. The occurrence of harms was generally not reported. Conclusion Physical activity can have important, and even life-saving, effects as secondary prevention of disease, but more and better trials are needed to fully assess its benefits and harms, in particular trials that compare exercise with drugs.

Surgery for obstructive sleep apnoea in adults

Abstract: Background Obstructive sleep apnoea/hypopnoea syndrome(OSAHS) is the periodic reduction or cessation of airflow during sleep. The syndrome is associated with loud snoring, disrupted sleep and observed apnoeas. Surgery for obstructive sleep apnoea/hypopnoea syndrome aims to alleviate symptoms of daytime sleepiness, improve quality of life, and reduce the signs of sleep apnoea recorded by polysomnography. Objectives The objective of this review was to assess the effects of any type of surgery for the treatment of the symptoms of obstructive sleep apnoea/hypopnoea syndrome in adults. Search methods We searched the Cochrane Airways Group Specialised Register and reference lists of articles. We contacted experts in the field, research dissemination bodies and other Cochrane Review Groups. Searches were current as of July 2008. Selection criteria Randomised trials comparing any surgical intervention for obstructive sleep apnoea/hypopnoea syndrome with other surgical or non-surgical interventions or no intervention. Data collection and analysis Two reviewers assessed electronic literature search results for possibly relevant studies. Characteristics and data from studies meeting the inclusion criteria were extracted and entered into RevMan 5. Main results Twelve studies (709 participants) of mixed risk of bias met the inclusion criteria. Data from ten studies were eligible for assessment in the review. The participants recruited to the studies had mixed levels of AHI, but tended to suffer from moderate daytime sleepiness where this was measured. No data could be pooled. Uvulopalatopharyngoplasty (UPPP) versus conservative management (one trial): An un-validated symptom score showed intermittent significant differences over a 12-month follow-up period. No differences in Polysomnography (PSG) outcomes were reported. Laser-assisted uvulopalatoplasty (LAUP) versus conservative management/placebo (two trials): One study recruited a mixed population and separate data could not be obtained for this trial. In the other study no significant differences in Epworth scores or quality of life reported. A significant difference in favour of LAUP was reported in terms of apnoea hypopnoea index (AHI) and frequency and intensity of snoring. Palatal implants versus placebo (one trial): Symptoms and AHI were lower with palatal implants. LAUP versus bipolar radiofrequency volumetric tissue reduction (one trial): Within-treatment group differences were significant for symptoms and AHI, but the between treatment group differences were not available to assess whether indirect inferences could be made regarding the effects of either treatment. UPPP versus oral appliance (OA) (one trial): AHI was significantly lower with OA therapy than with UPPP. No significant differences were observed in quality of life. UPPP versus lateral pharyngoplasty (lateral PP) (one trial): No significant difference in Epworth scores, but a greater reduction in AHI with lateral PP was reported. Expansion sphincter pharyngoplasty (one trial): Both interventions reduced AHI although statistical analysis on the difference between treatments was not reported. Tongue advancement (mandibular osteotomy) + PPP versus tongue suspension + PPP (one trial): There was a significant reduction in symptoms in both groups, but no significant difference between the two surgery types. Complications reported with all surgical techniques included nasal regurgitation, pain and bleeding. These did not persist in the long term. An additional study assessed the effects of four different techniques. No data were available on between group comparisons. Multilevel temperature-controlled radiofrequency tissue ablation (TCRFTA) versus sham placebo and CPAP (one trial): There was an improvement in primary and secondary outcomes of TCRFTA over sham placebo and but no difference in symptomatic improvement when compared with CPAP. Radiofrequency assisted uvulopalatoplasty technique versus channeling technique (one trial): Dysphagia scores were lower in the channeling group immediately post-operation, but at four months the difference was no longer significant. Snoring scores did not differ at long-term follow-up. The number of participants achieving AHI lower than 10 at four months was slightly higher with RAUP than channeling technique. Authors' conclusions There are now a small number of trials assessing different surgical techniques with inactive and active control treatments. The studies assembled in the review have failed to demonstrate consistent effects in favour of surgery and do not provide convincing evidence to support its use in sleep apnoea/hypopnoea syndrome. Short-term outcomes are unlikely to consistently identify suitable candidates for surgery. Long-term follow-up of patients who undergo surgical correction of upper airway obstruction is required. This would help to determine whether surgery is a curative intervention, or whether there is a tendency for the signs and symptoms of sleep apnoea to re-assert themselves, prompting patients to seek further treatment for sleep apnoea.

Is evidence-based medicine relevant to the developing world?

Abstract: Although there is still some resistance to the evidence-based medicine movement evidence-based health care has now become widely accepted and adopted. Systematic reviews of the effectiveness of health care interventions are the engine room of evidence-based health care; much has been written about how these reviews should be conducted and what they can achieve. If the case for the use of systematic reviews is good in developed countries--and we think it is--then the case is even stronger in the developing world. Wherever health care is provided and used it is essential to know which interventions work which do not work and which are likely to be harmful. This is especially important in situations where health problems are severe and the scarcity of resources makes it vital that they are not wasted. But are the systematic reviews that have so far been published relevant and of practical use to those who provide health care in "the majority world" (i.e. in developing countries). In our view the relevance of systematic reviews to frontline health care workers in developing countries has so far been limited for a number of reasons. (excerpt)

Laxatives for the treatment of hemorrhoids.

Abstract: Background Symptomatic hemorrhoids are a common medical condition, which increase in prevalence in women during pregnancy and postpartum. Although the evidence appears to be inconclusive, narrative reviews and clinical practice guidelines recommend the use of laxatives (and fiber) for the treatment of hemorrhoids and relief of symptoms. This is due to their safety and low cost. Objectives To evaluate the impact of laxatives on a wide range of symptoms in people with symptomatic hemorrhoids. Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005), MEDLINE (1966 to 2005), EMBASE (1980 to 2005), CINAHL (1982 to 2005), BIOSIS, and AMED (Allied and Alternative Medicine Database), for eligible trials (including conference proceedings). We sought missing and additional information from authors, industry, and experts in the field. Selection criteria We selected all published and unpublished randomised controlled trials that compared any type of laxative to placebo or no therapy in any patient population. Data collection and analysis Two authors independently screened studies for inclusion and retrieved all potentially relevant studies. Data were extracted from studies that met our selection criteria on study population, intervention used, pre-specified outcomes, and methodology. We extracted methodological information for the assessment of internal validity: existence and method of generation of the randomization schedule, and method of allocation concealment; blinding of caregivers and outcomes assessors; numbers of and reasons for participants lost to follow up; and use of validated outcome measures. Main results Seven randomised trials enrolling a total of 378 participants to fiber or a non-fiber control were identified. Meta-analyses using random-effects models showed that laxatives in the form of fiber had a beneficial effect in the treatment of symptomatic hemorrhoids. The risk of not improving hemorrhoids and having persisting symptoms decreased by 53% in the fiber group (risk reduction (RR) 0.47, 95% CI 0.32 to 0.68). These results are compatible with large treatment effects regarding prolapse, pain, itching, although the pooled analyses showed a tendency toward no-effect for these parametres. The effect on bleeding showed a significant difference in favour of the fiber (RR 0.50, 95% CI 0.28 to 0.89). Studies including data on multiple follow ups (usually after six weeks and three months) showed consistent results over time. However, we have to stress two possible limitations of this review: the risk of publication bias, and only moderate study quality. Authors' conclusions The use of fiber shows a consistent beneficial effect for relieving overall symptoms and bleeding in the treatment of symptomatic hemorrhoids.

High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with metastatic breast cancer.

Abstract: Background There is a hypothesis that high dose chemotherapy with autologous bone marrow or stem cell transplantation (autograft) may improve survival for women with metastatic breast cancer. Objectives To compare the effectiveness of high dose chemotherapy and autologous bone marrow or stem cell transplantation with conventional chemotherapy for women with metastatic breast cancer. Search strategy We used the Cochrane Breast Cancer Group search strategy, adding these terms: bone marrow transplantation, stem cell transplantation, autologous stem cell support. The following databases were searched: MEDLINE (until August 2002), EMBASE (until July 2002), ASCO (American Society of Clinical Oncology) (1995-2002) and the COCHRANE LIBRARY (Issue 3 2002). We searched the Cochrane Breast Cancer Group database and cooperative research groups' websites for unpublished trials. Selection criteria Randomised controlled trials comparing the effectiveness of high dose chemotherapy and autograft with conventional chemotherapy for women with metastatic breast cancer. Studies included one or more of the following outcomes: treatment related mortality, overall or progression-free survival at 1, 2, 3, 5 or 7 years, morbidity, quality of life measures, time to tumour progression, overall survival time. Data collection and analysis Five randomised controlled trials met the inclusion criteria. Two independent reviewers extracted data. Main results In total 382 women were randomised to receive high dose chemotherapy with autograft and 358 were randomised to receive conventional treatment. There were ten treatment related deaths among the high dose group and none reported in the control (conventional dose) group (RR 5.70, 95%CI (1.30, 25)). There was no statistically significant difference in overall survival between the high dose and control groups (at one year: RR 0.99, 95% CI (0.91, 1.08); three years: RR 1.16 95% CI (0.90, 1.51); five years: RR 1.28, 95% CI (0.72, 2.27)). At one and two years of follow up, a statistically significant difference in progression free survival was reported, favouring the high dose group (one year: RR 1.81, 95% CI (1.39,2.34); two years: RR 1.96, 95% CI (1.32, 2.90 ). However this difference was not evident at three or five years (three years: RR 1.44, 95% CI (0.85, 2.44); five years: RR 1.21, 95% CI (0.40, 3.69). Toxicity was more severe in the high dose group. None of the trials has completed follow up and further data are awaited. Reviewer's conclusions Although there is evidence that high dose chemotherapy and autograft improves progression free survival at one and two years' follow up compared to conventional chemotherapy, there is no evidence of benefit in overall survival.

Effectiveness of different databases in identifying studies for systematic reviews: experience from the WHO systematic review of maternal morbidity and mortality

Abstract: Failure to be comprehensive can distort the results of a systematic review. Conversely, extensive searches may yield unmanageable number of citations of which only few may be relevant. Knowledge of usefulness of each source of information may help to tailor search strategies in systematic reviews. We conducted a systematic review of prevalence/incidence of maternal mortality and morbidities from 1997 to 2002. The search strategy included electronic databases, hand searching, screening of reference lists, congress abstract books, contacting experts active in the field and web sites from less developed countries. We evaluated the effectiveness of each source of data and discuss limitations and implications for future research on this topic. Electronic databases identified 64098 different citations of which 2093 were included. Additionally 487 citations were included from other sources. MEDLINE had the highest yield identifying about 62% of the included citations. BIOSIS was the most precise with 13.2% of screened citations included. Considering electronic citations alone (2093), almost 20% were identified uniquely by MEDLINE (400), 7.4% uniquely by EMBASE (154), and 5.6% uniquely by LILACS (117). About 60% of the electronic citations included were identified by two or more databases. This analysis confirms the need for extending the search to other sources beyond well-known electronic databases in systematic reviews of maternal mortality and morbidity prevalence/incidence. These include regional databases such as LILACS and other topic specific sources such as hand searching of relevant journals not indexed in electronic databases. Guidelines for search strategies for prevalence/incidence studies need to be developed.

It's in your hands: the value of handsearching in conducting systematic reviews of public health interventions.

Abstract: Background While there is an emerging evidence base in public health, the evidence can often be difficult to find. Indexing of journals in MEDLINE has assisted those conducting systematic reviews to more easily identify published studies. However, information technology and the processes associated with indexing are not infallible. Studies may not be correctly marked by study design which may mean they are missed in the electronic searching process. Handsearching for evidence of intervention effectiveness has therefore become a recognized tool in the systematic review process. Methods Resources to guide handsearching activity currently are clinically focused, and may not be sensitive to the characteristics of public health studies where study terminology may differ. In response to this issue, the Cochrane Health Promotion and Public Health Field (the Field) developed and implemented a small study to recruit and support handsearchers from around the world to identify health promotion and public health trials and systematic reviews. A strategic framework was developed to recruit and support handsearchers to search six public health-related journals. Results In total, 131 trials and 21 systematic reviews were identified. The greatest value of handsearching was found to be in supplement editions and abstract sections of journals Conclusions The study focused exclusively on indexed journals with the intention that tools and methods developed could be used to explore the potential for handsearching in non-indexed journals and for unpublished studies. The findings from this study will continue to support handsearching efforts and in doing so contribute to high quality systematic reviews of public health interventions.

Correlating nerve conduction studies and clinical outcome measures on carpal tunnel syndrome: lessons from a randomized controlled trial.

Abstract: The reported relationships between nerve conduction studies (NCS) and outcome measures in carpal tunnel syndrome (CTS) are weak to moderate. However, selection of patients may have confounded nonrandomized studies. NCS have potentially great value in selecting patients for a specific treatment and in objectively assessing the efficacy of treatments in CTS, especially if they correlate significantly with clinical outcome measures. To investigate the relationship between clinical outcome measures for the severity of complaints and NCS in patients treated for CTS, data were obtained from a multicenter randomized controlled trial on the efficacy of splinting versus surgery for CTS. At baseline and 12 months after randomization, clinical outcome measures were assessed and NCS were performed. In total, 138 patients completed the questionnaires and underwent repeated NCS. Relationships were analyzed with Spearman rank correlation coefficients and Pearson correlation coefficients. All NCS parameters showed highly significant improvement compared with baseline (P < 0.001). Modest correlations (<0.4) were found between the neurophysiologic and clinical outcome measures after 12 months, and between the changes in these different categories of outcome measures. This study confirms that the parameters of NCS improve significantly after treatment for CTS, but the modest correlations between neurophysiologic and clinical outcome measures do not support that NCS are routinely performed in clinical practice to evaluate treatment effects. However, studies investigating the effects of treatment for CTS should incorporate both clinical outcome measures and NCS, because they are complementary. Furthermore, NCS can provide additional information to the clinician when treatment effects are unsatisfactory.

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

Abstract: 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.

Consumer-driven health care: Building partnerships in research

Abstract: Over the past four decades, there has been a widespread movement to increase the involvement of patients and the public in health care. Strategies to effectively foster consumer participation are occurring within all research activities from research priority setting to utilization. One of the ten principles of the Cochrane Collaboration is to enable wide participation, and this includes consumers. The Cochrane Musculoskeletal Group (CMSG) is a review group of 50 within the Collaboration that has been working to increase consumer participation since its inception in 1993. Based in Canada, the CMSG has embraced the concept of knowledge translation as advocated by the Canadian Institutes of Health Research. The emphasis in knowledge translation is on interactions or partnerships between researchers and users to facilitate the use of relevant research in decision making. While the CMSG recognizes the importance of reaching all users, much of its work has focused on developing relationships with people with musculoskeletal diseases to enhance consumer participation in research. The CMSG has built a network of consumer members who guide research priorities, peer review systematic reviews and also promote and facilitate consumerappropriate knowledge dissemination. Consumers were recruited through links with other arthritis organizations and the recruitment continues. Specific roles were established for the consumer team and responsibilities of the CMSG staff developed. The continuing development of a diversified team of consumer participants enables the CMSG to produce and promote access to high quality relevant systematic reviews and summaries of those reviews to the consumer.

Promoting the social and emotional health of primary school-aged children: reviewing the evidence base for school-based interventions

Abstract: Schools are key settings for promoting the social and emotional health and well-being of children. This study investigated the effectiveness of interventions to improve the social and emotional well-being of primary school-aged children. The protocol development stage of the proposed systematic review identified related and comparable research reviews, indicating a more useful review of reviews. Eight reviews of intervention effectiveness covering 322 primary studies were reviewed. The majority examined classroom-based interventions. Greater effectiveness results from a sustained focus on the promotion of mental health, on self-esteem and coping outcomes within the broad school climate, and on replicating positive impacts rather than the prevention of mental health problems. Conclusions are limited by short duration of studies, lack of detail of interventions, identified outcomes and socio-demographic data, and the relationship between processes and outcomes. This study has clearly shown how crucial carefully designed studies are in understanding strategies with potential to impact on the mental health and well-being of children.

Randomised controlled trials in Africa of HIV and AIDS: descriptive study and spatial distribution.

Abstract: Objectives To identify and describe randomised controlled trials on HIV and AIDS conducted in Africa and to map their spatial distribution using exact geographic coordinates. Design Construction and analysis of a database of trials conducted wholly or partly in Africa and reported before 2004. Data sources CENTRAL, Medline, Embase, and LILACS. Results Our comprehensive search yielded 284 distinct records that were potentially eligible for inclusion in the database. Of these, 150 articles reported on 77 eligible trials published or reported from 1987 to 2003. Seven trials were identified exclusively from the CENTRAL database. Trials were conducted in 18 of 48 countries in sub-Saharan Africa. None were conducted in north Africa. Only 19 had a principal investigator located in an African country. Forty two trials assessed prevention and 35 assessed treatment. Most studies were funded by government agencies outside Africa (n = 43), with the pharmaceutical industry providing partial support to 16 of these. The pharmaceutical industry provided full or partial support to a further 18 trials. Only 43 trials reported conducting a power calculation for determining sample size. There was no mention of ethical approval or informed consent in 19 and 17 trials, respectively. Conclusion The relatively small number of HIV/AIDS trials conducted in Africa is not commensurate with the burden of disease. Geographical mapping as an adjunct to prospective trial registration is a useful tool for researchers and decision makers to track existing and future trials.

Are experimental treatments for cancer in children superior to established treatments? Observational study of randomised controlled trials by the Children's Oncology Group.

Abstract: Objectives To assess how often new treatments for childhood cancer assessed in phase III randomised trials are superior or inferior to standard treatments and whether the pattern of successes and failures in new treatments is consistent with uncertainty being the ethical basis for enrolling patients in such trials. Design Observational study. Setting Phase III randomised controlled trials carried out under the aegis of the Children9s Oncology Group between 1955 and 1997, regardless of whether they were published. Main outcome measures Overall survival, event free survival, and treatment related mortality. Results 126 trials were included, involving 152 comparisons and 36 567 patients. The odds ratio for overall survival with experimental treatments was 0.96 (99% confidence interval 0.89 to 1.03), indicating that new treatments are as likely to be inferior as they are to be superior to standard treatments. This result was not affected by publication bias, methodological quality, treatment type, disease, or comparator. Conclusions New treatments in childhood cancer tested in randomised controlled trials are, on average, as likely to be inferior as they are to be superior to standard treatments, confirming that the uncertainty principle has been operating.

Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis

Abstract: To determine whether ingestion of milk thistle affects the pharmacokinetics of indinavir. We conducted a three-period, randomized controlled trial with 16 healthy participants. We randomized participants to milk thistle or control. All participants received initial dosing of indinavir, and baseline indinavir levels were obtained (AUC0-8) (phase I). The active group were then given 450 mg milk-thistle extract capsules to be taken t.i.d. from day 2 to day 30. The control group received no plant extract. On day 29 and day 30, indinavir dosing and sampling was repeated in both groups as before (phase II). After a wash-out period of 7 days, indinavir dosing and sampling were repeated as before (phase III). All participants completed the trial, but two were excluded from analysis due to protocol violation. There were no significant between-group differences. Active group mean AUC0-8 indinavir decreased by 4.4% (90% CI, −27.5% to −26%, P=0.78) from phase I to phase II in the active group, and by 17.3% (90% CI, −37.3% to +9%, P=0.25) in phase III. Control group mean AUC0-8 decreased by 21.5% (90% CI, −43% to +8%, P=0.2) from phase I to phase II and by 38.5% (90% CI, −55.3% to −15.3%, P=0.01) of baseline at phase III. To place our findings in context, milk thistle–indinavir trials were identified through systematic searches of the literature. A meta-analysis of three milk thistle–indinavir trials revealed a non-significant pooled mean difference of 1% in AUC0-8 (95% CI, −53% to 55%, P=0.97). Indinavir levels were not reduced significantly in the presence of milk thistle.