Why are medical and health-related studies not being published? A systematic review of reasons given by investigators

Objective: About half of medical and health related studies are not published. We conducted a systematic review of reports on reasons given by investigators for not publishing their studies in peer-reviewed journals. Methods: MEDLINE, EMBASE, PsycINFO, and SCOPUS (until 13/09/2013), and references of identified articles were searched to identify reports of surveys that provided data on reasons given by investigators for not publishing studies. The proportion of non-submission and reasons for non-publication was calculated using the number of unpublished studies as the denominator. Because of heterogeneity across studies, quantitative pooling was not conducted. Exploratory subgroup analyses were conducted. Results: We included 54 survey reports. Data from 38 included reports were available to estimate proportions of at least one reason given for not publishing studies. The proportion of non-submission among unpublished studies ranged from 55% to 100%, with a median of 85%. The reasons given by investigators for not publishing their studies included: lack of time or low priority (median 33%), studies being incomplete (median 15%), study not for publication (median 14%), manuscript in preparation or under review (median 12%), unimportant or negative result (median 12%), poor study quality or design (median 11%), fear of rejection (median 12%), rejection by journals (median 6%), author or co-author problems (median 10%), and sponsor or funder problems (median 9%). In general, the frequency of reasons given for non-publication was not associated with the source of unpublished studies, study design, or time when a survey was conducted. Conclusions: Non-submission of studies for publication remains the main cause of non-publication of studies. Measures to reduce non-publication of studies and alternative models of research dissemination need to be developed to address the main reasons given by investigators for not publishing their studies, such as lack of time or low priority and fear of being rejected by journals

Presence and persistence of Ebola or Marburg virus in patients and survivors: A rapid systematic review

Background: The 2013-15 Ebola outbreak was unprecedented due to sustainedtransmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods: Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. [1] Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results: 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions: Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood

'Mediterranean' dietary pattern for the primary prevention of cardiovascular disease

It is well established that diet plays a major role in cardiovascular disease risk. The traditional Mediterranean dietary pattern is of particular interest because of observations from the 1960s that populations in countries of the Mediterranean region, such as Greece and Italy, had lower mortality from cardiovascular disease compared with northern European populations or the US, probably as a result of different eating habits. This review assessed the effects of providing dietary advice to follow a Mediterranean-style dietary pattern to healthy adults or people at increased risk of cardiovascular disease in order to prevent the occurrence of cardiovascular disease and reduce the risk factors associated with it. Definitions of a Mediterranean dietary pattern vary and we included only randomised controlled trials (RCTs) of interventions that reported at least two of the following components: (1) high monounsaturated/saturated fat ratio, (2) low to moderate red wine consumption, (3) high consumption of legumes, (4) high consumption of grains and cereals, (5) high consumption of fruits and vegetables, (6) low consumption of meat and meat products and increased consumption of fish, and (7) moderate consumption of milk and dairy products. The control group was no intervention or minimal intervention. We found 11 RCTs (15 papers) that met these criteria. The trials varied enormously in the participants recruited and the different dietary interventions. Four trials were conducted in women only, two trials were in men only and the remaining five were in both men and women. Five trials were conducted in healthy individuals and six trials were in people at increased risk of cardiovascular disease or cancer. The number of components relevant to a Mediterranean dietary pattern ranged from two to five and only seven trials described the intervention as a Mediterranean diet. The largest trial, which recruited only postmenopausal women and was not described as a Mediterranean diet meeting only two of the criteria described above, reported no difference in the occurrence of cardiovascular disease between the dietary advice group and the control group. The other trials measured risk factors for cardiovascular disease. As the studies were so different, it was not possible to combine studies for most of the outcomes. Where it was possible to combine studies, we found small reductions in total cholesterol levels as well as in the harmful low-density lipoprotein (LDL) cholesterol concentrations. The reductions in total cholesterol were greater in the studies that described themselves as providing a Mediterranean diet. None of the trials reported side effects. The review concludes that, from the limited evidence to date, a Mediterranean dietary pattern reduces some cardiovascular risk factors. However, more trials are needed to look at the effects of the different participants recruited and the different dietary interventions to see which interventions might work best in different populations

What is the evidence of the impact of microfinance on the well-being of poor people?

The concept of microcredit was first introduced in Bangladesh by Nobel Peace Prize winner Muhammad Yunus. Professor Yunus started Grameen Bank (GB) more than 30 years ago with the aim of reducing poverty by providing small loans to the country’s rural poor (Yunus 1999). Microcredit has evolved over the years and does not only provide credit to the poor, but also now spans a myriad of other services including savings, insurance, remittances and non-financial services such as financial literacy training and skills development programmes; microcredit is now referred to as microfinance (Armendáriz de Aghion and Morduch 2005, 2010). A key feature of microfinance has been the targeting of women on the grounds that, compared to men, they perform better as clients of microfinance institutions and that their participation has more desirable development outcomes (Pitt and Khandker 1998). Despite the apparent success and popularity of microfinance, no clear evidence yet exists that microfinance programmes have positive impacts (Armendáriz de Aghion and Morduch 2005, 2010; and many others). There have been four major reviews examining impacts of microfinance (Sebstad and Chen, 1996; Gaile and Foster 1996, Goldberg 2005, Odell 2010, see also Orso 2011). These reviews concluded that, while anecdotes and other inspiring stories (such as Todd 1996) purported to show that microfinance can make a real difference in the lives of those served, rigorous quantitative evidence on the nature, magnitude and balance of microfinance impact is still scarce and inconclusive (Armendáriz de Aghion and Morduch 2005, 2010). Overall, it is widely acknowledged that no well-known study robustly shows any strong impacts of microfinance (Armendáriz de Aghion and Morduch 2005, p199-230). Because of the growth of the microfinance industry and the attention the sector has received from policy makers, donors and private investors in recent years, existing microfinance impact evaluations need to be re-investigated; the robustness of claims that microfinance successfully alleviates poverty and empowers women must be scrutinised more carefully. Hence, this review revisits the evidence of microfinance evaluations focusing on the technical challenges of conducting rigorous microfinance impact evaluations

A survey of orthopaedic journal editors determining the criteria of manuscript selection for publication

Background: To investigate the characteristics of editors and criteria used by orthopaedic journal editors in assessing submitted manuscripts. Methods: Between 2008 to 2009 all 70 editors of Medline listed orthopaedic journals were approached prospectively with a questionnaire to determine the criteria used in assessing manuscripts for publication. Results: There was a 42% response rate. There was 1 female editor and the rest were male with 57% greater than 60 years of age. 67% of the editors worked in university teaching hospitals and 90% of publications were in English.The review process differed between journals with 59% using a review proforma, 52% reviewing an anonymised manuscript, 76% using a routine statistical review and 59% of journals used 2 reviewers routinely. In 89% of the editors surveyed, the editor was able to overrule the final decision of the reviewers.Important design factors considered for manuscript acceptance were that the study conclusions were justified (80%), that the statistical analysis was appropriate (76%), that the findings could change practice (72%). The level of evidence (70%) and type of study (62%) were deemed less important. When asked what factors were important in the manuscript influencing acceptance, 73% cited an understandable manuscript, 53% cited a well written manuscript and 50% a thorough literature review as very important factors. Conclusions: The editorial and review process in orthopaedic journals uses different approaches. There may be a risk of language bias among editors of orthopaedic journals with under-representation of non-English publications in the orthopaedic literature

Green and black tea for the primary prevention of cardiovascular disease

Background: There is increasing evidence that both green and black tea are beneficial for cardiovascular disease (CVD) prevention. Objectives: To determine the effects of green and black tea on the primary prevention of CVD. Search methods: We searched the following databases on 12 October 2012 without language restrictions: CENTRAL in The Cochrane Library, MEDLINE (OVID), EMBASE (OVID) and Web of Science (Thomson Reuters). We also searched trial registers, screened reference lists and contacted authors for additional information where necessary. Selection criteria: Randomised controlled trials (RCTs) lasting at least three months involving healthy adults or those at high risk of CVD. Trials investigated the intake of green tea, black tea or tea extracts. The comparison group was no intervention, placebo or minimal intervention. The outcomes of interest were CVD clinical events and major CVD risk factors. Any trials involving multifactorial lifestyle interventions or focusing on weight loss were excluded to avoid confounding. Data collection and analysis: Two review authors independently selected trials for inclusion, abstracted data and assessed the risk of bias. Trials of green tea were analysed separately from trials of black tea. Main results: We identified 11 RCTs with a total of 821 participants, two trials awaiting classification and one ongoing trial. Seven trials examined a green tea intervention and four examined a black tea intervention. Dosage and form of both green and black tea differed between trials. The ongoing trial is examining the effects of green tea powder capsules. No studies reported cardiovascular events. Black tea was found to produce statistically significant reductions in low-density lipoprotein (LDL) cholesterol (mean difference (MD) -0.43 mmol/L, 95% confidence interval (CI) -0.56 to -0.31) and blood pressure (systolic blood pressure (SBP): MD -1.85 mmHg, 95% CI -3.21 to -0.48. Diastolic blood pressure (DBP): MD -1.27 mmHg, 95% CI -3.06 to 0.53) over six months, stable to sensitivity analysis, but only a small number of trials contributed to each analysis and studies were at risk of bias. Green tea was also found to produce statistically significant reductions in total cholesterol (MD -0.62 mmol/L, 95% CI -0.77 to - 0.46), LDL cholesterol (MD -0.64 mmol/L, 95% CI -0.77 to -0.52) and blood pressure (SBP: MD -3.18 mmHg, 95% CI -5.25 to - 1.11; DBP: MD -3.42, 95% CI -4.54 to -2.30), but only a small number of studies contributed to each analysis, and results were not stable to sensitivity analysis. When both tea types were analysed together they showed favourable effects on LDL cholesterol (MD - 0.48 mmol/L, 95% CI -0.61 to -0.35) and blood pressure (SBP: MD -2.25 mmHg, 95% CI -3.39 to -1.11; DBP: MD -2.81 mmHg, 95% CI -3.77 to -1.86). Adverse events were measured in five trials and included a diagnosis of prostate cancer, hospitalisation for influenza, appendicitis and retinal detachment but these are unlikely to be directly attributable to the intervention. Authors' conclusions: There are very few long-term studies to date examining green or black tea for the primary prevention of CVD. The limited evidence suggests that tea has favourable effects on CVD risk factors, but due to the small number of trials contributing to each analysis the results should be treated with some caution and further high quality trials with longer-term follow-up are needed to confirm this

Effect of lower sodium intake on health: systematic review and meta-analyses

Objective To assess the effect of decreased sodium intake on blood pressure, related cardiovascular diseases, and potential adverse effects such as changes in blood lipids, catecholamine levels, and renal function. Design Systematic review and meta-analysis. Data sources Cochrane Central Register of Controlled Trials, Medline, Embase, WHO International Clinical Trials Registry Platform, the Latin American and Caribbean health science literature database, and the reference lists of previous reviews. Study selection Randomised controlled trials and prospective cohort studies in non-acutely ill adults and children assessing the relations between sodium intake and blood pressure, renal function, blood lipids, and catecholamine levels, and in non-acutely ill adults all cause mortality, cardiovascular disease, stroke, and coronary heart disease. Study appraisal and synthesis Potential studies were screened independently and in duplicate and study characteristics and outcomes extracted. When possible we conducted a meta-analysis to estimate the effect of lower sodium intake using the inverse variance method and a random effects model. We present results as mean differences or risk ratios, with 95% confidence intervals. Results We included 14 cohort studies and five randomised controlled trials reporting all cause mortality, cardiovascular disease, stroke, or coronary heart disease; and 37 randomised controlled trials measuring blood pressure, renal function, blood lipids, and catecholamine levels in adults. Nine controlled trials and one cohort study in children reporting on blood pressure were also included. In adults a reduction in sodium intake significantly reduced resting systolic blood pressure by 3.39 mm Hg (95% confidence interval 2.46 to 4.31) and resting diastolic blood pressure by 1.54 mm Hg (0.98 to 2.11). When sodium intake was 0.05). There were insufficient randomised controlled trials to assess the effects of reduced sodium intake on mortality and morbidity. The associations in cohort studies between sodium intake and all cause mortality, incident fatal and non-fatal cardiovascular disease, and coronary heart disease were non-significant (P>0.05). Increased sodium intake was associated with an increased risk of stroke (risk ratio 1.24, 95% confidence interval 1.08 to 1.43), stroke mortality (1.63, 1.27 to 2.10), and coronary heart disease mortality (1.32, 1.13 to 1.53). In children, a reduction in sodium intake significantly reduced systolic blood pressure by 0.84 mm Hg (0.25 to 1.43) and diastolic blood pressure by 0.87 mm Hg (0.14 to 1.60). Conclusions High quality evidence in non-acutely ill adults shows that reduced sodium intake reduces blood pressure and has no adverse effect on blood lipids, catecholamine levels, or renal function, and moderate quality evidence in children shows that a reduction in sodium intake reduces blood pressure. Lower sodium intake is also associated with a reduced risk of stroke and fatal coronary heart disease in adults. The totality of evidence suggests that most people will likely benefit from reducing sodium intake

Creation of a database to assess effects of omega-3, omega-6 and total polyunsaturated fats on health: methodology for a set of systematic reviews

Objective To create a database of long-term RCTs comparing higher with lower omega-3, omega-6 or total PUFA, regardless of reported outcomes, and develop methods to assess effects of increasing omega-6, ALA, LCn3 and total PUFA on health outcomes. Design Systematic review search, methodology and meta-analyses. Data Sources Medline, Embase, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov, and trials in relevant systematic reviews. Eligibility Criteria Randomised controlled trials (RCTs) of ≥24 weeks duration assessing effects of increasing alpha-linolenic acid (ALA), long-chain omega-3 (LCn3), omega-6 or total polyunsaturated fats (PUFA), regardless of outcomes reported Data Synthesis Methods included random-effects meta-analyses, sensitivity analyses. Funnel plots were examined and subgrouping assessed effects of intervention type, replacement, baseline diabetes risk and use of diabetic medications, trial duration and dose. Quality of evidence was assessed using GRADE. Results Electronic searches generated 37,810 hits, de-duplicated to 19,772 titles and abstracts. We assessed 2155 full text papers, conference abstracts and trials registry entries independently in duplicate. Included studies were grouped into 363 RCTs comparing higher with lower omega-3, omega-6 and/or total PUFA intake of at least 6 months duration – the Database. Of these 363 included RCTs, 216 RCTs were included in at least one of our reviews of health outcomes, data extracted and risk of bias assessed in duplicate (Dataset 1, Supplementary File 1). Ninety five RCTs were included in the database but not included in our current reviews (Dataset 2, Supplementary File 2). Of these 311 completed trials, 27 altered ALA intake, 221 altered LCn3 intake, and 16 trials altered omega-3 intake without specifying whether ALA or LCn3. Forty one trials altered omega-6 fats and 59 total PUFA. The remaining 52 trials (Dataset 3, Supplementary File 3) are ongoing though 13 (25%) appear to be outstanding, or constitute missing data. Conclusions This extensive database of trials is available to allow assessment of further health outcomes