Systematic reviews of complementary therapies – an annotated bibliography. Part 3: Homeopathy

Background Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with homeopathy. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of homeopathy; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pretested form and summarized descriptively. Results Eighteen out of 22 potentially relevant reviews preselected in the screening process met the inclusion criteria. Six reviews addressed the question whether homeopathy is effective across conditions and interventions. The majority of available trials seem to report positive results but the evidence is not convincing. For isopathic nosodes for allergic conditions, oscillococcinum for influenza-like syndromes and galphimia for pollinosis the evidence is promising while in other areas reviewed the results are equivocal. Interpretation Reviews on homeopathy often address general questions. While the evidence is promising for some topics the findings of the available reviews are unlikely to end the controversy on this therapy

Physical activity and risk of comorbidities in patients with chronic obstructive pulmonary disease: a cohort study

Multi-morbidity is common in patients with chronic obstructive pulmonary disease and low levels of physical activity are hypothesized to be an important risk factor. The current study aimed to assess the longitudinal association between physical activity and risk of seven categories of comorbidity in chronic obstructive pulmonary disease patients. The study included 409 patients from primary care practice in the Netherlands and Switzerland. We assessed physical activity using the Longitudinal Ageing Study Amsterdam Physical Activity Questionnaire at baseline and followed patients for up to 5 years. During follow-up, patients reported their comorbidities (cardiovascular, neurological, endocrine, musculoskeletal, malignant, and infectious diseases) and completed the Hospital Anxiety and Depression Scale questionnaire for mental health assessment. We implemented multinomial logistic regression (an approximation to discrete time survival model using death as a competing risk) for our analysis. Study results did not suggest a statistically significant association of baseline physical activity with the development of seven categories of comorbidity. However, when we focused on depression and anxiety symptoms, we found that higher levels of physical activity at baseline were associated with a lower risk for depression (adjusted hazard ratio, 0.85; 0.75-0.95; p = 0.005) and anxiety (adjusted hazard ratio, 0.89; 0.79-1.00; p = 0.045). In chronic obstructive pulmonary disease patients, those with high physical activity are less likely to develop depression or anxiety symptoms over time. Increasing physical activity in chronic obstructive pulmonary disease patients may be an approach for testing to lower the burden from incident depression and anxiet

Identifying Diagnostic Studies in MEDLINE: Reducing the Number Needed to Read

Objectives: The search filters in PubMed have become a cornerstone in information retrieval in evidence-based practice. However, the filter for diagnostic studies is not fully satisfactory, because sensitive searches have low precision. The objective of this study was to construct and validate better search strategies to identify diagnostic articles recorded on MEDLINE with special emphasis on precision. Design: A comparative, retrospective analysis was conducted. Four medical journals were hand-searched for diagnostic studies published in 1989 and 1994. Four other journals were hand-searched for 1999. The three sets of studies identified were used as gold standards. A new search strategy was constructed and tested using the 1989-subset of studies and validated in both the 1994 and 1999 subsets. We identified candidate text words for search strategies using a word frequency analysis of the abstracts. According to the frequency of identified terms, searches were run for each term independently. The sensitivity, precision, and number needed to read (1/precision) of every candidate term were calculated. Terms with the highest sensitivity × precision product were used as free text terms in combination with the MeSH term "SENSITIVITY AND SPECIFICITY” using the Boolean operator OR. In the 1994 and 1999 subsets, we performed head-to-head comparisons of the currently available PubMed filter with the one we developed. Measurements: The sensitivity, precision and the number needed to read (1/precision) were measured for different search filters. Results: The most frequently occurring three truncated terms (diagnos*; predict* and accura*) in combination with the MeSH term "SENSITIVITY AND SPECIFICITY” produced a sensitivity of 98.1 percent (95% confidence interval: 89.9-99.9%) and a number needed to read of 8.3 (95% confidence interval: 6.7-11.3%). In direct comparisons of the new filter with the currently available one in PubMed using the 1994 and 1999 subsets, the new filter achieved better precision (12.0% versus 8.2% in 1994 and 5.0% versus 4.3% in 1999. The 95% confidence intervals for the differences range from 0.05% to 7.5% (p = 0.041) and -1.0% to 2.3% (p = 0.45), respectively). The new filter achieved slightly better sensitivities than the currently available one in both subsets, namely 98.1 and 96.1% (p = 0.32) versus 95.1 and 88.8% (p = 0.125). Conclusions: The quoted performance of the currently available filter for diagnostic studies in PubMed may be overstated. It appears that even single external validation may lead to over optimistic views of a filter's performance. Precision appears to be more unstable than sensitivity. In terms of sensitivity, our filter for diagnostic studies performed slightly better than the currently available one and it performed better with regards to precision in the 1994 subset. Additional research is required to determine whether these improvements are beneficial to searches in practic

A protocol improves GP recording of long-term sickness absence risk factors

Background If general practitioners (GPs) were better informed about patients' risks of long-term sickness absence (LTSA), they could incorporate these risk assessments into their patient management plans and cooperate more with occupational physicians to prevent LTSA. Aim To evaluate the effectiveness of a protocol helping GPs in recording risks of LTSA and in co-operating with occupational physicians (OPs). Methods Twenty-six GPs (co-operating in four groups) in Amsterdam, The Netherlands, participated in a controlled intervention study. Fourteen GPs were the protocol-supported intervention group and twelve GPs were the reference group. Outcome measures were consultations containing work-related information, information about two risk factors for LTSA, referrals to OPs and contacts of OPs with GPs and patients. Outcomes were identified through an electronic search in the GPs' information systems. Entries containing information were independently scored by two investigators. The proportions of patients with consultations documenting LTSA-pertinent items were compared between the groups, accounting for differences at baseline. Results There was no increase in consultations containing work-related information. Recording of risk factor information increased in the intervention group; the difference was 4.5% [95% CI 1.5-7.6] and 1.8% (95% CI −0.8 to 4.4) for the two risk factors. The referral rate to the OP increased by 2.9% (95% CI 1.2-4.5). There was no effect on contacts of OPs with GPs or with patients. Conclusion Protocol-supported consultations may lead to a modest increase in information regarding two risk factors for LTSA in GPs' electronic records and to more referrals to OP

Where is the supporting evidence for treating mild to moderate chronic obstructive pulmonary disease exacerbations with antibiotics? A systematic review

BACKGROUND: Randomised trials comparing different drugs head-to-head are extremely valuable for clinical decision-making. However, it is scientifically and ethically sensible to demand strong evidence that a drug is effective by showing superiority over a placebo before embarking on head-to-head comparisons of potentially ineffective drugs. Our aim was to study the evolvement of evidence from placebo-controlled and head-to-head trials on the effects of antibiotics for the treatment of mild to moderate exacerbations of chronic obstructive pulmonary disease. METHODS: We conducted a historical systematic review. Through electronic databases and hand-searches, we identified placebo-controlled and head-to-head antibiotic trials for the treatment of mild to moderate chronic obstructive pulmonary disease exacerbations. We compared the numbers of patients recruited in placebo-controlled and head-to-head trials between 1957 and 2005. Using cumulative meta-analysis of placebo-controlled trials, we determined when, if ever, placebo-controlled trials had shown convincing evidence that antibiotics are effective in preventing treatment failure in patients with mild to moderate chronic obstructive pulmonary disease exacerbations. RESULTS: The first head-to-head trial was published in 1963. It was followed by another 100 trials comparing different antibiotics in a total of 34,029 patients with mild to moderate chronic obstructive pulmonary disease exacerbations. Over time, the cumulative odds ratio in placebo-controlled trials remained inconclusive throughout with odds ratios ranging from 0.39 (95% confidence intervals 0.04-4.22) to the most recent estimate (1995) of 0.81 (95% confidence intervals 0.52-1.28, P = 0.37). CONCLUSION: Placebo-controlled trials do not support the use of antibiotics in chronic obstructive pulmonary disease patients with mild to moderate exacerbations. Conducting head-to-head trials is, therefore, scientifically and ethically questionable. This underscores the requirement to perform or study systematic reviews of placebo-controlled trials before conducting head-to-head trials

Impact of Stressful Life Events on Patients with Chronic Obstructive Pulmonary Disease

Background: There is a general notion that stressful life events may cause mental and physical health problems. Objectives: We aimed to describe stressful life events reported by patients with chronic obstructive pulmonary disease (COPD) and to assess their impact on health outcomes and behaviors. Methods: Two hundred and sixty-six primary care patients who participated in the ICE COLD ERIC cohort study were asked to document any stressful life events in the past 3 years. We assessed the before-after (the event) changes for symptoms of depression and anxiety, health status, dyspnea-related quality of life, exacerbations, cigarette use, and physical activity. We used linear regression analysis to estimate the crude and adjusted magnitude of the before-after changes. Results: About 41% (110/266) of patients reported the experience of any stressful life events and “death of relatives/important persons” was most common (31%). After accounting for age, sex, living status, lung function, and anxiety/depression status at baseline, experiencing any stressful life events was associated with a 0.9-point increase on the depression scale (95% CI 0.3 to 1.4), a 0.8-point increase on the anxiety scale (95% CI 0.3 to 1.3), and a 0.8-point decrease in the physical activity score (95% CI –1.6 to 0). Conclusions: Experiencing stressful life events was associated with a small to moderate increase in symptoms of depression and anxiety in COPD, but no discernable effect was found for other physical outcomes. However, confirmation of these results in other COPD cohorts and identification of patients particularly vulnerable to stressful life events are needed

Discussing study limitations in reports of biomedical studies- the need for more transparency

Unbiased and frank discussion of study limitations by authors represents a crucial part of the scientific discourse and progress. In today's culture of publishing many authors or scientific teams probably balance 'utter honesty' when discussing limitations of their research with the risk of being unable to publish their work. Currently, too few papers in the medical literature frankly discuss how limitations could have affected the study findings and interpretations. The goals of this commentary are to review how limitations are currently acknowledged in the medical literature, to discuss the implications of limitations in biomedical studies, and to make suggestions as to how to openly discuss limitations for scientists submitting their papers to journals. This commentary was developed through discussion and logical arguments by the authors who are doing research in the area of hedging (use of language to express uncertainty) and who have extensive experience as authors and editors of biomedical papers. We strongly encourage authors to report on all potentially important limitations that may have affected the quality and interpretation of the evidence being presented. This will not only benefit science but also offers incentives for authors: If not all important limitations are acknowledged readers and reviewers of scientific articles may perceive that the authors were unaware of them. Authors should take advantage of their content knowledge and familiarity with the study to prevent misinterpretations of the limitations by reviewers and readers. Articles discussing limitations help shape the future research agenda and are likely to be cited because they have informed the design and conduct of future studies. Instead of perceiving acknowledgment of limitations negatively, authors, reviewers and editors should recognize the potential of a frank and unbiased discussion of study limitations that should not jeopardize acceptance of manuscripts

Systematic reviews of complementary therapies - an annotated bibliography. Part 1: Acupuncture

Background Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with acupuncture. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of acupuncture; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pretested form and summarized descriptively. Results From a total of 48 potentially relevant reviews preselected in a screeening process 39 met the inclusion criteria. 22 were on various pain syndromes or rheumatic diseases. Other topics addressed by more than one review were addiction, nausea, asthma and tinnitus. Almost unanimously the reviews state that acupuncture trials include too few patients. Often included trials are heterogeneous regarding patients, interventions and outcome measures, are considered to have insufficient quality and contradictory results. Convincing evidence is available only for postoperative nausea, for which acupuncture appears to be of benefit, and smoking cessation, where acupuncture is no more effective than sham acupuncture. Conclusions A large number of systematic reviews on acupuncture exists. What is most obvious from these reviews is the need for (the funding of) well-designed, larger clinical trials

Prevalence of questionable research practices, research misconduct and their potential explanatory factors:A survey among academic researchers in The Netherlands

Prevalence of research misconduct, questionable research practices (QRPs) and their associations with a range of explanatory factors has not been studied sufficiently among academic researchers. The National Survey on Research Integrity targeted all disciplinary fields and academic ranks in the Netherlands. It included questions about engagement in fabrication, falsification and 11 QRPs over the previous three years, and 12 explanatory factor scales. We ensured strict identity protection and used the randomized response method for questions on research misconduct. 6,813 respondents completed the survey. Prevalence of fabrication was 4.3% (95% CI: 2.9, 5.7) and of falsification 4.2% (95% CI: 2.8, 5.6). Prevalence of QRPs ranged from 0.6% (95% CI: 0.5, 0.9) to 17.5% (95% CI: 16.4, 18.7) with 51.3% (95% CI: 50.1, 52.5) of respondents engaging frequently in at least one QRP. Being a PhD candidate or junior researcher increased the odds of frequently engaging in at least one QRP, as did being male. Scientific norm subscription (odds ratio (OR) 0.79; 95% CI: 0.63, 1.00) and perceived likelihood of detection by reviewers (OR 0.62, 95% CI: 0.44, 0.88) were associated with engaging in less research misconduct. Publication pressure was associated with more often engaging in one or more QRPs frequently (OR 1.22, 95% CI: 1.14, 1.30). We found higher prevalence of misconduct than earlier surveys. Our results suggest that greater emphasis on scientific norm subscription, strengthening reviewers in their role as gatekeepers of research quality and curbing the “publish or perish” incentive system promotes research integrity