A Web-Based Health Application to Translate Nutrition Therapy for Cardiovascular Risk Reduction in Primary Care (PortfolioDiet.app): Quality Improvement and Usability Testing Study.

BACKGROUND: The Portfolio Diet, or Dietary Portfolio, is a therapeutic dietary pattern that combines cholesterol-lowering foods to manage dyslipidemia for the prevention of cardiovascular disease. To translate the Portfolio Diet for primary care, we developed the PortfolioDiet.app as a patient and physician educational and engagement tool for PCs and smartphones. The PortfolioDiet.app is currently being used as an add-on therapy to the standard of care (usual care) for the prevention of cardiovascular disease in primary care. To enhance the adoption of this tool, it is important to ensure that the PortfolioDiet.app meets the needs of its target end users. OBJECTIVE: The main objective of this project is to undertake user testing to inform modifications to the PortfolioDiet.app as part of ongoing engagement in quality improvement (QI). METHODS: We undertook a 2-phase QI project from February 2021 to September 2021. We recruited users by convenience sampling. Users included patients, family physicians, and dietitians, as well as nutrition and medical students. For both phases, users were asked to use the PortfolioDiet.app daily for 7 days. In phase 1, a mixed-form questionnaire was administered to evaluate the users' perceived acceptability, knowledge acquisition, and engagement with the PortfolioDiet.app. The questionnaire collected both quantitative and qualitative data, including 2 open-ended questions. The responses were used to inform modifications to the PortfolioDiet.app. In phase 2, the System Usability Scale was used to assess the usability of the updated PortfolioDiet.app, with a score higher than 70 being considered acceptable. RESULTS: A total of 30 and 19 users were recruited for phase 1 and phase 2, respectively. In phase 1, the PortfolioDiet.app increased users' perceived knowledge of the Portfolio Diet and influenced their perceived food choices. Limitations identified by users included challenges navigating to resources and profile settings, limited information on plant sterols, inaccuracies in points, timed-logout frustration, request for step-by-step pop-up windows, and request for a mobile app version; when looking at positive feedback, the recipe section was the most commonly praised feature. Between the project phases, 6 modifications were made to the PortfolioDiet.app to incorporate and address user feedback. At phase 2, the average System Usability Scale score was 85.39 (SD 11.47), with 100 being the best possible. CONCLUSIONS: By undertaking user testing of the PortfolioDiet.app, its limitations and strengths were able to be identified, informing modifications to the application, which resulted in a clinical tool that better meets users' needs. The PortfolioDiet.app educates users on the Portfolio Diet and is considered acceptable by users. Although further refinements to the PortfolioDiet.app will continue to be made before its evaluation in a clinical trial, the result of this QI project is an improved clinical tool.

Effect of transcutaneous electrical nerve stimulation (TENS) on knee pain and physical function in patients with symptomatic knee osteoarthritis: the ETRELKA randomized clinical trial.

OBJECTIVE: To determine the effectiveness of TENS at relieving pain and improving physical function as compared to placebo TENS, and to determine its safety, in patients with knee osteoarthritis. METHODS: Multi-centre, parallel, 1:1 randomized, double-blind, placebo-controlled clinical trial conducted in six outpatient clinics in Switzerland. We included 220 participants with knee osteoarthritis recruited between October 15, 2012, and October 15, 2014. Patients were randomized to 3 weeks of treatment with TENS (n = 108) or placebo TENS (n = 112). Our pre-specified primary endpoint was knee pain at the end of 3-weeks treatment assessed with the WOMAC pain subscale. Secondary outcome measures included WOMAC physical function subscale and safety outcomes. RESULTS: There was no difference between TENS and placebo TENS in WOMAC pain at the end of treatment (mean difference -0.06; 95%CI -0.41 to 0.29; P = 0.74), nor throughout the trial duration (P = 0.98). Subgroup analyses did not indicate an interaction between patient/treatment characteristics and treatment effect on WOMAC pain at the end of treatment (P-interaction ≥0.22). The occurrence of adverse events was similar across groups, with 10.4% and 10.6% of patients reporting events in the TENS and placebo TENS groups, respectively (P = 0.95). No relevant differences were observed in secondary outcomes. CONCLUSIONS: TENS does not improve knee osteoarthritis pain when compared to placebo TENS. Therapists should consider other potentially more effective treatment modalities to decrease knee osteoarthritis pain and facilitate strengthening and aerobic exercise. Our findings are conclusive and further trials comparing TENS and placebo TENS in this patient population are not necessary.

Single early palliative care intervention added to usual oncology care for patients with advanced cancer: A randomized controlled trial (SENS Trial).

BACKGROUND: International oncology societies recommend early palliative care. Specific models to integrate early palliative care efficiently into clinical practice are debated. The authors designed a study to look at the quantitative and qualitative outcomes of an early palliative care intervention in oncological care to decrease stress and improve quality of life. AIMS: To compare a single structured early palliative care intervention added to a usual oncology care in terms of distress and health-related quality of life at baseline compared to 6 months after enrollment. DESIGN: This multicenter randomized controlled trial (NCT01983956) enrolled adult patients with advanced cancer. Participants were either randomly assigned to usual oncology care alone or usual care plus a structured early palliative care intervention. SETTING/PARTICIPANTS: One hundred fifty adult patients with a variety of advanced cancer diagnoses were randomized. Seventy-four participants were in the intervention and 76 participants in the control group. The primary outcome was the change in patient distress assessed by the National Comprehensive Cancer Network distress thermometer at 6 months. Health-related quality of life, the secondary outcome, was assessed by the Functional Assessment of Cancer Therapy-General Questionnaire. RESULTS: The results showed no significant effect of the early palliative care intervention neither on patient distress nor on health-related quality of life. CONCLUSION: The addition of an early intervention to usual care for patients with advanced cancer did not improve distress or quality of life. Thus, patients may need more intensive early palliative care with continuous professional support to identify and address their palliative needs early.

Visual Analogue Scale has higher assay sensitivity than WOMAC pain in detecting between-group differences in treatment effects: a meta-epidemiological study.

OBJECTIVE: To compare assay sensitivity of the Visual Analogue Scale (VAS) for global osteoarthritis pain and the Western Ontario and McMaster University (WOMAC) pain subscale, and the associated between-trial heterogeneity in effect sizes (ES). DESIGN: We included trials with placebo, sham or non-intervention control that included at least 100 patients with hip or knee osteoarthritis per arm, reporting both VAS and WOMAC pain scores. ES were calculated as between-group difference in means divided by the pooled standard deviation and compared using a paired t-test. ES and τ2 as a measure of between-trial heterogeneity were combined using random-effects meta-regression with robust variance estimation to account for the correlation of data within trials and meta-analyses. RESULTS: Twenty-eight trials with 44 randomized comparisons were included. In 28 comparisons (64%), ES from VAS favoured the intervention more than those from WOMAC pain (P = 0.003). Twenty-six p-values (59%) were smaller according to VAS (P = 0.008). The 44 comparisons contributed to 12 meta-analyses. Eleven meta-analyses (92%) showed larger benefits of interventions according to VAS, with a combined overall difference in ES of -0.08 (95% CI -0.14 to -0.02). τ2 was similar for VAS and WOMAC pain (difference in τ2, -0.003, 95% CI -0.009 to 0.004). CONCLUSION: The VAS for global pain had slightly higher assay sensitivity at trial and meta-analysis levels than the WOMAC pain subscale without relevant increase in between-trial heterogeneity.

The effects of intravenous iron supplementation on fatigue and general health in non-anemic blood donors with iron deficiency: a randomized placebo-controlled superiority trial.

We investigated whether intravenous iron supplementation improves fatigue and general health in non-anemic repeat adult blood donors with iron deficiency (ferritin ≤ 50 µg/L). Of 1,487 potentially eligible participants, 203 were randomly assigned to a single intravenous dose of 800 mg iron-carboxymaltose and 202 to placebo; 393 participants completed the trial. At 6 to 8 weeks after intervention, self-rated mean fatigue scores (numeric rating scale from 1-10, primary outcome) were 3.9 ± 1.8 in the iron supplementation group and 4.0 ± 2.2 in the placebo group, showing no group difference (p = 0.819). Pre-specified subgroup analyses of gender, ferritin < 25 µg/L and fatigue ≥ 4 points, as well as exploratory analyses of lower ferritin cut-offs did not reveal any between-group differences. In terms of secondary outcomes, the mean differences were 114.2 µg/L for ferritin (95% CI 103.1-125.3) and 5.7 g/L for hemoglobin (95% CI 4.3-7.2) with significantly higher values in the iron supplementation group. No group differences were observed for different measures of general well-being and other clinical and safety outcomes. Intravenous iron supplementation compared with placebo resulted in increase of ferritin and hemoglobin levels in repeat blood donors with low iron stores, yet had no effect on fatigue and general well-being.

Sono-electro-magnetic therapy for treating chronic pelvic pain syndrome in men: a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: To assess the efficacy and safety of sono-electro-magnetic therapy compared to placebo in men with refractory CPPS. PATIENTS AND METHODS: In a randomized, placebo-controlled, double-blind single center trial, we assessed the effect of sono-electro-magnetic therapy in men with treatment refractory CPPS. Sixty male patients were randomly assigned to treatment with either sono-electro-magnetic (n = 30) or placebo therapy (n = 30) for 12 weeks. The primary outcome was a change in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) from baseline to 12 weeks. RESULTS: The 12-week difference between sono-electro-magnetic and placebo therapy in changes of the NIH-CPSI total score was -3.1 points (95% CI -6.8 to 0.6, p = 0.11). In secondary comparisons of NIH-CPSI sub-scores, we found differences between groups most pronounced for the quality-of-life sub-score (difference at 12 weeks -1.6, 95% CI -2.8 to -0.4, p = 0.015). In stratified analyses, the benefit of sono-electro-magnetic therapy appeared more pronounced among patients who had a symptom duration of 12 months or less (difference in NIH-CPSI total score -8.3, 95% CI -14.5 to 2.6) than in patients with a longer symptom duration (-0.8, 95% CI -4.6 to 3.1; p for interaction = 0.023). CONCLUSIONS: Sono-electro-magnetic therapy did not result in a significant improvement of symptoms in the overall cohort of treatment refractory CPPS patients compared to placebo treatment. Subgroup analysis indicates, however, that patients with a symptom-duration of 12 months or less may benefit from sono-electro-magnetic therapy, warranting larger randomized controlled trials in this subpopulation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00688506.

Omega-3 poly-unsaturated fatty acids for the prevention of severe neutropenic enterocolitis in patients with acute myeloid leukemia.

Neutropenic enterocolitis is a potentially fatal complication of myeloablative chemotherapy in patients with acute myeloid leukemia. Omega-3 polyunsaturated fatty acids (PUFA) are precursors of potent anti-inflammatory prostaglandins. Our aim was to explore the safety and effectiveness of omega-3 PUFA added to parenteral nutrition in protecting leukemia patients from severe enterocolitis. Fourteen patients with acute myeloid leukemia who received omega-3 PUFA in a Phase II trial were compared with 66 consecutive control patients not getting this intervention. We performed crude and adjusted comparisons, using inverse probability of treatment weighting for adjusted analysis, and blind outcome assessment to minimize assessor bias. Primary outcome was severe enterocolitis (≥Grade 3). The crude odds ratio of Grade 3 colitis or higher was 1.36 (95% CI 0.37 to 4.96, P = 0.64), and the adjusted odds ratio was 0.79 (95% CI 0.35 to 1.78, P = 0.57). There was little evidence to suggest differences between groups in serious adverse events and overall mortality. Our results provide little evidence that addition of omega-3 PUFA is beneficial in this condition. Routine treatment with omega-3 PUFA is currently not warranted.

Comparative efficacy of pharmacological and non-pharmacological interventions in fibromyalgia syndrome: network meta-analysis.

OBJECTIVES: To synthesise the available evidence on pharmacological and non-pharmacological interventions recommended for fibromyalgia syndrome (FMS). METHODS: Electronic databases including MEDLINE, PsycINFO, Scopus, the Cochrane Controlled Trials Registry and the Cochrane Library were searched for randomised controlled trials comparing any therapeutic approach as recommended in FMS guidelines (except complementary and alternative medicine) with control interventions in patients with FMS. Primary outcomes were pain and quality of life. Data extraction was done using standardised forms. RESULTS: 102 trials in 14 982 patients and eight active interventions (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors (SNRIs), the gamma-amino butyric acid analogue pregabalin, aerobic exercise, balneotherapy, cognitive behavioural therapy (CBT), multicomponent therapy) were included. Most of the trials were small and hampered by methodological quality, introducing heterogeneity and inconsistency in the network. When restricted to large trials with ≥100 patients per group, heterogeneity was low and benefits for SNRIs and pregabalin compared with placebo were statistically significant, but small and not clinically relevant. For non-pharmacological interventions, only one large trial of CBT was available. In medium-sized trials with ≥50 patients per group, multicomponent therapy showed small to moderate benefits over placebo, followed by aerobic exercise and CBT. CONCLUSIONS: Benefits of pharmacological treatments in FMS are of questionable clinical relevance and evidence for benefits of non-pharmacological interventions is limited. A combination of pregabalin or SNRIs as pharmacological interventions and multicomponent therapy, aerobic exercise and CBT as non-pharmacological interventions seems most promising for the management of FMS.

The importance of allocation concealment and patient blinding in osteoarthritis trials: a meta-epidemiologic study.

OBJECTIVE: To evaluate the association of adequate allocation concealment and patient blinding with estimates of treatment benefits in osteoarthritis trials. METHODS: We performed a meta-epidemiologic study of 16 meta-analyses with 175 trials that compared therapeutic interventions with placebo or nonintervention control in patients with hip or knee osteoarthritis. We calculated effect sizes from the differences in means of pain intensity between groups at the end of followup divided by the pooled SD and compared effect sizes between trials with and trials without adequate methodology. RESULTS: Effect sizes tended to be less beneficial in 46 trials with adequate allocation concealment compared with 112 trials with inadequate or unclear concealment of allocation (difference -0.15; 95% confidence interval [95% CI] -0.31, 0.02). Selection bias associated with inadequate or unclear concealment of allocation was most pronounced in meta-analyses with large estimated treatment benefits (P for interaction < 0.001), meta-analyses with high between-trial heterogeneity (P = 0.009), and meta-analyses of complementary medicine (P = 0.019). Effect sizes tended to be less beneficial in 64 trials with adequate blinding of patients compared with 58 trials without (difference -0.15; 95% CI -0.39, 0.09), but differences were less consistent and disappeared after accounting for allocation concealment. Detection bias associated with a lack of adequate patient blinding was most pronounced for nonpharmacologic interventions (P for interaction < 0.001). CONCLUSION: Results of osteoarthritis trials may be affected by selection and detection bias. Adequate concealment of allocation and attempts to blind patients will minimize these biases.

Transcutaneous electrostimulation for osteoarthritis of the knee.

BACKGROUND: Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in the elderly. Transcutaneous electrical nerve stimulation (TENS), interferential current stimulation and pulsed electrostimulation are used widely to control both acute and chronic pain arising from several conditions, but some policy makers regard efficacy evidence as insufficient. OBJECTIVES: To compare transcutaneous electrostimulation with sham or no specific intervention in terms of effects on pain and withdrawals due to adverse events in patients with knee osteoarthritis. SEARCH STRATEGY: We updated the search in CENTRAL, MEDLINE, EMBASE, CINAHL and PEDro up to 5 August 2008, checked conference proceedings and reference lists, and contacted authors. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared transcutaneously applied electrostimulation with a sham intervention or no intervention in patients with osteoarthritis of the knee. DATA COLLECTION AND ANALYSIS: We extracted data using standardised forms and contacted investigators to obtain missing outcome information. Main outcomes were pain and withdrawals or dropouts due to adverse events. We calculated standardised mean differences (SMDs) for pain and relative risks for safety outcomes and used inverse-variance random-effects meta-analysis. The analysis of pain was based on predicted estimates from meta-regression using the standard error as explanatory variable. MAIN RESULTS: In this update we identified 14 additional trials resulting in the inclusion of 18 small trials in 813 patients. Eleven trials used TENS, four interferential current stimulation, one both TENS and interferential current stimulation, and two pulsed electrostimulation. The methodological quality and the quality of reporting was poor and a high degree of heterogeneity among the trials (I(2) = 80%) was revealed. The funnel plot for pain was asymmetrical (P < 0.001). The predicted SMD of pain intensity in trials as large as the largest trial was -0.07 (95% CI -0.46 to 0.32), corresponding to a difference in pain scores between electrostimulation and control of 0.2 cm on a 10 cm visual analogue scale. There was little evidence that SMDs differed on the type of electrostimulation (P = 0.94). The relative risk of being withdrawn or dropping out due to adverse events was 0.97 (95% CI 0.2 to 6.0). AUTHORS' CONCLUSIONS: In this update, we could not confirm that transcutaneous electrostimulation is effective for pain relief. The current systematic review is inconclusive, hampered by the inclusion of only small trials of questionable quality. Appropriately designed trials of adequate power are warranted.

The effects of excluding patients from the analysis in randomised controlled trials: meta-epidemiological study.

OBJECTIVE: To examine whether excluding patients from the analysis of randomised trials are associated with biased estimates of treatment effects and higher heterogeneity between trials. DESIGN: Meta-epidemiological study based on a collection of meta-analyses of randomised trials. DATA SOURCES: 14 meta-analyses including 167 trials that compared therapeutic interventions with placebo or non-intervention control in patients with osteoarthritis of the hip or knee and used patient reported pain as an outcome. METHODS: Effect sizes were calculated from differences in means of pain intensity between groups at the end of follow-up, divided by the pooled standard deviation. Trials were combined by using random effects meta-analysis. Estimates of treatment effects were compared between trials with and trials without exclusions from the analysis, and the impact of restricting meta-analyses to trials without exclusions was assessed. RESULTS: 39 trials (23%) had included all patients in the analysis. In 128 trials (77%) some patients were excluded from the analysis. Effect sizes from trials with exclusions tended to be more beneficial than those from trials without exclusions (difference -0.13, 95% confidence interval -0.29 to 0.04). However, estimates of bias between individual meta-analyses varied considerably (tau(2)=0.07). Tests of interaction between exclusions from the analysis and estimates of treatment effects were positive in five meta-analyses. Stratified analyses indicated that differences in effect sizes between trials with and trials without exclusions were more pronounced in meta-analyses with high between trial heterogeneity, in meta-analyses with large estimated treatment benefits, and in meta-analyses of complementary medicine. Restriction of meta-analyses to trials without exclusions resulted in smaller estimated treatment benefits, larger P values, and considerable decreases in between trial heterogeneity. CONCLUSION: Excluding patients from the analysis in randomised trials often results in biased estimates of treatment effects, but the extent and direction of bias is unpredictable. Results from intention to treat analyses should always be described in reports of randomised trials. In systematic reviews, the influence of exclusions from the analysis on estimated treatment effects should routinely be assessed.

Determinants of reduced walking speed in people with musculoskeletal pain.

OBJECTIVE: Maintenance of good walking speed is essential to independent living. People with musculoskeletal disease often have reduced walking speed. We investigated determinants of slower walking, other than musculoskeletal disease, that might provide valuable additional targets for therapy. METHODS: We analyzed data from the Somerset and Avon Survey of Health, a community based survey of people aged over 35 years. A total of 2703 participants who reported hip or knee pain at baseline (1994/1995) were studied, and reassessed in 2002-2003; 1696 were available for followup, and walking speed was tested in 1074. Walking speed (m/s) was used as outcome measure. Baseline characteristics, including comorbidities and socioeconomic factors, were tested for their ability to predict reduced walking speed using multiple linear regression analysis. RESULTS: Age, female sex, and immobility at baseline were predictive of slower walking speed. Other independent risk factors included the presence of cataract, low socioeconomic status, intermittent claudication, and other cardiovascular conditions. Having a cataract was associated with a decrease of 0.10 m/s (95% CI 0.03, 0.16). Those in social class V had a walking speed 0.22 m/s (95% CI 0.126, 0.31) slower than those in social class I. CONCLUSION: Comorbidities, age, female sex, and lower socioeconomic position determine walking speed in people with joint pain. Issues such as poor vision and social-economic disadvantage may add to the effect of musculoskeletal disease, suggesting the need for a holistic approach to management of these patients.

Matched-pair study showed higher quality of placebo-controlled trials in Western phytotherapy than conventional medicine.

OBJECTIVES: Herbal medicine (phytotherapy) is widely used, but the evidence for its effectiveness is a matter of ongoing debate. We compared the quality and results of trials of Western phytotherapy and conventional medicine. STUDY DESIGN AND SETTING: A random sample of placebo-controlled trials of Western phytotherapy was identified in a comprehensive literature search (19 electronic databases). Conventional medicine trials matched for condition and type of outcome were selected from the Cochrane Central Controlled Trials Register (issue 1, 2003). Data were extracted in duplicate. Trials described as double-blind, with adequate generation of allocation sequence and adequate concealment of allocation were assumed to be of higher methodological quality. RESULTS: Eighty-nine herbal medicine and 89 matched conventional medicine trials were analyzed. Studies of Western herbalism were smaller, less likely to be published in English, and less likely to be indexed in MEDLINE than their counterparts from conventional medicine. Nineteen (21%) herbal and four (5%) conventional medicine trials were of higher quality. In both groups, smaller trials showed more beneficial treatment effects than larger trials. CONCLUSIONS: Our findings challenge the widely held belief that the quality of the evidence on the effectiveness of herbal medicine is generally inferior to the evidence available for conventional medicine.

Placebo-controlled trials of Chinese herbal medicine and conventional medicine comparative study.

BACKGROUND: Chinese herbal medicine (CHM) is increasingly used in the West, but the evidence on its effectiveness is a matter of debate. We compared the characteristics, study quality and results of clinical trials of CHM and conventional medicine. METHODS: Comparative study of placebo-controlled trials of CHM and conventional medicine. Eleven bibliographic databases and searches by hand of 48 Chinese-language journals. Conventional medicine trials matched for condition and type of outcome were randomly selected from the Cochrane Controlled Trials Register (issue 1, 2003). Trials described as double-blind, with adequate generation of allocation sequence and adequate concealment of allocation, were assumed to be of high quality. Data were analysed using funnel plots and multivariable meta-regression models. RESULTS: 136 CHM trials (119 published in Chinese, 17 published in English) and 136 matched conventional medicine trials (125 published in English) were analysed. The quality of Chinese-language CHM trials tended to be lower than that of English-language CHM trials and conventional medicine trials. Three (2%) CHM trials and 10 (7%) conventional medicine trials were of high quality. In all groups, smaller trials showed more beneficial treatment effects than larger trials. CHM trials published in Chinese showed considerably larger effects than CHM trials published in English (adjusted ratio of ORs 0.29, 95% confidence intervals 0.17-0.52). CONCLUSIONS: Biases are present both in placebo-controlled trials of CHM and conventional medicine, but may be most pronounced in CHM trials published in Chinese-language journals. Only few CHM trials of adequate methodology exist and the effectiveness of CHM therefore remains poorly documented.

Osteoarthritis: rational approach to treating the individual.

Osteoarthritis (OA) is the most common form of joint disease and the leading cause of pain and physical disability in older people. Risk factors for incidence and progression of osteoarthritis vary considerably according to the type of joint. Disease assessment is difficult and the relationship between the radiographic severity of joint damage and the incidence and severity of pain is only modest. Psychosocial and socio-economic factors play an important role. This chapter will discuss four main guiding principles to the management of OA: (1) to avoid overtreating people with mild symptoms; (2) to attempt to avoid doing more harm than good ('primum non nocere'); (3) to base patient management on the severity of pain, disability and distress, and not on the severity of joint damage or radiographic change; and (4) to start with advice about simple measures that patients can take to help themselves, and only progress to interventions that require supervision or specialist knowledge if simple measures fail. Effect sizes derived from meta-analyses of large randomized trials in OA are only small to moderate for most therapeutic interventions, but they are still valuable for patients and clinically relevant for physicians. Joint replacement may be the only option with a large effect size, but is only appropriate for the relatively small number of people with OA who have advanced disease and severe symptoms. The key to successful management involves patient and health professionals working together to develop optimal treatment strategies for the individual.

Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy.

BACKGROUND: Homoeopathy is widely used, but specific effects of homoeopathic remedies seem implausible. Bias in the conduct and reporting of trials is a possible explanation for positive findings of trials of both homoeopathy and conventional medicine. We analysed trials of homoeopathy and conventional medicine and estimated treatment effects in trials least likely to be affected by bias. METHODS: Placebo-controlled trials of homoeopathy were identified by a comprehensive literature search, which covered 19 electronic databases, reference lists of relevant papers, and contacts with experts. Trials in conventional medicine matched to homoeopathy trials for disorder and type of outcome were randomly selected from the Cochrane Controlled Trials Register (issue 1, 2003). Data were extracted in duplicate and outcomes coded so that odds ratios below 1 indicated benefit. Trials described as double-blind, with adequate randomisation, were assumed to be of higher methodological quality. Bias effects were examined in funnel plots and meta-regression models. FINDINGS: 110 homoeopathy trials and 110 matched conventional-medicine trials were analysed. The median study size was 65 participants (range ten to 1573). 21 homoeopathy trials (19%) and nine (8%) conventional-medicine trials were of higher quality. In both groups, smaller trials and those of lower quality showed more beneficial treatment effects than larger and higher-quality trials. When the analysis was restricted to large trials of higher quality, the odds ratio was 0.88 (95% CI 0.65-1.19) for homoeopathy (eight trials) and 0.58 (0.39-0.85) for conventional medicine (six trials). INTERPRETATION: Biases are present in placebo-controlled trials of both homoeopathy and conventional medicine. When account was taken for these biases in the analysis, there was weak evidence for a specific effect of homoeopathic remedies, but strong evidence for specific effects of conventional interventions. This finding is compatible with the notion that the clinical effects of homoeopathy are placebo effects.

Effect of a flow chart on use of blood transfusions in primary total hip and knee replacement: prospective before and after study.

PROBLEM: A suspected high proportion of unnecessary blood transfusions occur in patients undergoing total joint replacement. DESIGN: Prospective before and after study evaluating the impact of a one page flow chart aimed at reducing the use of blood transfusions. SETTING: Orthopaedic tertiary care centre in Winterthur, Switzerland. 208 patients underwent primary total joint replacement of hips or knees during the control period (October 1998 to September 1999) and 217 during the intervention period (October 1999 to September 2000). KEY MEASURES FOR IMPROVEMENT: Proportion of patients receiving allogeneic blood transfusions. STRATEGIES FOR CHANGE: A simple one page flow chart, which summarised graphically the perioperative decision pathways for anaemic patients, was placed in all charts of patients undergoing total joint replacement and handed out to medical staff from 4 October 1999 onwards. The implementation of the flow chart focused on its endorsement by chief physicians and the development of a sense of "ownership" among physicians and nurses. EFFECTS OF CHANGE: The proportion of patients receiving allogeneic blood decreased from 35.0% to 19.8% (absolute difference -15.2%, 95% confidence interval -23.3 to -7.0%). The percentage of patients donating and receiving autologous blood also decreased. This led to overall savings of about 23,000 pounds sterling (42,470 dollars; 34,441 euros) (103.50 pounds sterlingper patient undergoing total joint replacement). Differences became more pronounced after adjustment for confounding factors. LESSONS LEARNT: Allogeneic blood transfusions in primary hip and knee replacement surgery may be reduced cost effectively by implementing a one page flow chart. Five key elements may have contributed: simplicity; wide distribution; no requirement for major changes; endorsement by local opinion leaders; and development of a sense of ownership. These elements may be used in other contexts to achieve sustained change of clinical practice.

Acupuncture for alcohol withdrawal: a randomized controlled trial.

BACKGROUND AND AIMS: Previous trials on acupuncture in alcohol addiction were in outpatients and focused on relapse prevention. Rates of dropout were high and interpretation of results difficult. We compared auricular laser and needle acupuncture with sham laser stimulation in reducing the duration of alcohol withdrawal. METHODS: Inpatients undergoing alcohol withdrawal were randomly allocated to laser acupuncture (n = 17), needle acupuncture (n = 15) or sham laser stimulation (n = 16). Attempts were made to blind patients, therapists and outcome assessors, but this was not feasible for needle acupuncture. The duration of withdrawal symptoms (as assessed using a nurse-rated scale) was the primary outcome; the duration of sedative prescription was the secondary outcome. RESULTS: Patients randomized to laser and sham laser had identical withdrawal symptom durations (median 4 days). Patients randomized to needle stimulation had a shorter duration of withdrawal symptoms (median 3 days; P = 0.019 versus sham intervention), and tended to have a shorter duration of sedative use, but these differences diminished after adjustment for baseline differences. CONCLUSIONS: The data from this pilot trial do not suggest a relevant benefit of auricular laser acupuncture for alcohol withdrawal. A larger trial including adequate sham interventions is needed, however, to reliably determine the effectiveness of any type of auricular acupuncture in this condition.