Systematic review finds that study data not published in full text articles have unclear impact on meta-analyses results in medical research.

A meta-analysis as part of a systematic review aims to provide a thorough, comprehensive and unbiased statistical summary of data from the literature. However, relevant study results could be missing from a meta-analysis because of selective publication and inadequate dissemination. If missing outcome data differ systematically from published ones, a meta-analysis will be biased with an inaccurate assessment of the intervention effect. As part of the EU-funded OPEN project (www.open-project.eu) we conducted a systematic review that assessed whether the inclusion of data that were not published at all and/or published only in the grey literature influences pooled effect estimates in meta-analyses and leads to different interpretation. Systematic review of published literature (methodological research projects). Four bibliographic databases were searched up to February 2016 without restriction of publication year or language. Methodological research projects were considered eligible for inclusion if they reviewed a cohort of meta-analyses which (i) compared pooled effect estimates of meta-analyses of health care interventions according to publication status of data or (ii) examined whether the inclusion of unpublished or grey literature data impacts the result of a meta-analysis. Seven methodological research projects including 187 meta-analyses comparing pooled treatment effect estimates according to different publication status were identified. Two research projects showed that published data showed larger pooled treatment effects in favour of the intervention than unpublished or grey literature data (Ratio of ORs 1.15, 95% CI 1.04-1.28 and 1.34, 95% CI 1.09-1.66). In the remaining research projects pooled effect estimates and/or overall findings were not significantly changed by the inclusion of unpublished and/or grey literature data. The precision of the pooled estimate was increased with narrower 95% confidence interval. Although we may anticipate that systematic reviews and meta-analyses not including unpublished or grey literature study results are likely to overestimate the treatment effects, current empirical research shows that this is only the case in a minority of reviews. Therefore, currently, a meta-analyst should particularly consider time, effort and costs when adding such data to their analysis. Future research is needed to identify which reviews may benefit most from including unpublished or grey data

Extent of non-publication in cohorts of studies approved by research ethics committees or included in trial registries

BACKGROUND: The synthesis of published research in systematic reviews is essential when providing evidence to inform clinical and health policy decision-making. However, the validity of systematic reviews is threatened if journal publications represent a biased selection of all studies that have been conducted (dissemination bias). To investigate the extent of dissemination bias we conducted a systematic review that determined the proportion of studies published as peer-reviewed journal articles and investigated factors associated with full publication in cohorts of studies (i) approved by research ethics committees (RECs) or (ii) included in trial registries. METHODS AND FINDINGS: Four bibliographic databases were searched for methodological research projects (MRPs) without limitations for publication year, language or study location. The searches were supplemented by handsearching the references of included MRPs. We estimated the proportion of studies published using prediction intervals (PI) and a random effects meta-analysis. Pooled odds ratios (OR) were used to express associations between study characteristics and journal publication. Seventeen MRPs (23 publications) evaluated cohorts of studies approved by RECs; the proportion of published studies had a PI between 22% and 72% and the weighted pooled proportion when combining estimates would be 46.2% (95% CI 40.2%-52.4%, I2 = 94.4%). Twenty-two MRPs (22 publications) evaluated cohorts of studies included in trial registries; the PI of the proportion published ranged from 13% to 90% and the weighted pooled proportion would be 54.2% (95% CI 42.0%-65.9%, I2 = 98.9%). REC-approved studies with statistically significant results (compared with those without statistically significant results) were more likely to be published (pooled OR 2.8; 95% CI 2.2-3.5). Phase-III trials were also more likely to be published than phase II trials (pooled OR 2.0; 95% CI 1.6-2.5). The probability of publication within two years after study completion ranged from 7% to 30%. CONCLUSIONS: A substantial part of the studies approved by RECs or included in trial registries remains unpublished. Due to the large heterogeneity a prediction of the publication probability for a future study is very uncertain. Non-publication of research is not a random process, e.g., it is associated with the direction of study findings. Our findings suggest that the dissemination of research findings is biased

Mindfulness-based stress reduction for women diagnosed with breast cancer

Background Breast cancer is the most common cancer in women. Diagnosis and treatment may drastically affect quality of life, causing symptoms such as sleep disorders, depression and anxiety. Mindfulness-based stress reduction (MBSR) is a programme that aims to reduce stress by developing mindfulness, meaning a non-judgmental, accepting moment-by-moment awareness. MBSR seems to benefit patients with mood disorders and chronic pain, and it may also benefit women with breast cancer. Objectives To assess the effects of mindfulness-based stress reduction (MBSR) in women diagnosed with breast cancer. Search methods In April 2018, we conducted a comprehensive electronic search for studies of MBSR in women with breast cancer, in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and two trial registries (World Health Organization's International Clinical Trials Registry Platform WHO ICTRP) and ClinicalTrials.gov ). We also handsearched relevant conference proceedings. Selection criteria Randomised clinical trials (RCTs) comparing MBSR versus no intervention in women with breast cancer. Data collection and analysis We used standard methodological procedures expected by Cochrane. Using a standardised data form, the review authors extracted data in duplicate on methodological quality, participants, interventions and outcomes of interest (quality of life, fatigue, depression, anxiety, quality of sleep, overall survival and adverse events). For outcomes assessed with the same instrument, we used the mean difference (MD) as a summary statistic for meta-analysis; for those assessed with different instruments, we used the standardised mean difference (SMD). The effect of MBSR was assessed in the short term (end of intervention), medium term (up to 6 months after intervention) and long term (up to 24 months after intervention). Main results Fourteen RCTs fulfilled our inclusion criteria, with most studies reporting that they included women with early breast cancer. Ten RCTs involving 1571 participants were eligible for meta-analysis, while four studies involving 185 participants did not report usable results. Queries to the authors of these four studies were unsuccessful. All studies were at high risk of performance and detection bias since participants could not be blinded, and only 3 of 14 studies were at low risk of selection bias. Eight of 10 studies included in the meta-analysis recruited participants with early breast cancer (the remaining 2 trials did not restrict inclusion to a certain cancer type). Most trials considered only women who had completed cancer treatment. MBSR may improve quality of life slightly at the end of the intervention (based on low-certainty evidence from three studies with a total of 339 participants) but may result in little to no difference up to 6 months (based on low-certainty evidence from three studies involving 428 participants). Long-term data on quality of life (up to two years after completing MBSR) were available for one study in 97 participants (MD 0.00 on questionnaire FACT-B, 95% CI -5.82 to 5.82; low-certainty evidence). In the short term, MBSR probably reduces fatigue (SMD -0.50, 95% CI -0.86 to -0.14; moderate-certainty evidence; 5 studies; 693 participants). It also probably slightly reduces anxiety (SMD -0.29, 95% CI -0.50 to -0.08; moderate-certainty evidence; 6 studies; 749 participants), and it reduces depression (SMD -0.54, 95% CI -0.86 to -0.22; high-certainty evidence; 6 studies; 745 participants). It probably slightly improves quality of sleep (SMD -0.38, 95% CI -0.79 to 0.04; moderate-certainty evidence; 4 studies; 475 participants). However, these confidence intervals (except for short-term depression) are compatible with both an improvement and little to no difference. In the medium term, MBSR probably results in little to no difference in medium-term fatigue (SMD -0.31, 95% CI -0.84 to 0.23; moderate-certainty evidence; 4 studies; 607 participants). The intervention probably slightly reduces anxiety (SMD -0.28, 95% CI -0.49 to -0.07; moderate-certainty evidence; 7 studies; 1094 participants), depression (SMD -0.32, 95% CI -0.58 to -0.06; moderate-certainty evidence; 7 studies; 1097 participants) and slightly improves quality of sleep (SMD -0.27, 95% CI -0.63 to 0.08; moderate-certainty evidence; 4 studies; 654 participants). However, these confidence intervals are compatible with both an improvement and little to no difference. In the long term, moderate-certainty evidence shows that MBSR probably results in little to no difference in anxiety (SMD -0.09, 95% CI -0.35 to 0.16; 2 studies; 360 participants) or depression (SMD -0.17, 95% CI -0.40 to 0.05; 2 studies; 352 participants). No long-term data were available for fatigue or quality of sleep. No study reported data on survival or adverse events. Authors' conclusions MBSR may improve quality of life slightly at the end of the intervention but may result in little to no difference later on. MBSR probably slightly reduces anxiety, depression and slightly improves quality of sleep at both the end of the intervention and up to six months later. A beneficial effect on fatigue was apparent at the end of the intervention but not up to six months later. Up to two years after the intervention, MBSR probably results in little to no difference in anxiety and depression; there were no data available for fatigue or quality of sleep

The evolutionary consequences of human–wildlife conflict in cities

Human–wildlife interactions, including human–wildlife conflict, are increasingly common as expanding urbanization worldwide creates more opportunities for people to encounter wildlife. Wildlife–vehicle collisions, zoonotic disease transmission, property damage, and physical attacks to people or their pets have negative consequences for both people and wildlife, underscoring the need for comprehensive strategies that mitigate and prevent conflict altogether. Management techniques often aim to deter, relocate, or remove individual organisms, all of which may present a significant selective force in both urban and nonurban systems. Managementinduced selection may significantly affect the adaptive or nonadaptive evolutionary processes of urban populations, yet few studies explicate the links among conflict, wildlife management, and urban evolution. Moreover, the intensity of conflict management can vary considerably by taxon, public perception, policy, religious and cultural beliefs, and geographic region, which underscores the complexity of developing flexible tools to reduce conflict. Here, we present a cross-disciplinary perspective that integrates human–wildlife conflict, wildlife management, and urban evolution to address how social–ecological processes drive wildlife adaptation in cities. We emphasize that variance in implemented management actions shapes the strength and rate of phenotypic and evolutionary change. We also consider how specific management strategies either promote genetic or plastic changes, and how leveraging those biological inferences could help optimize management actions while minimizing conflict. Investigating human–wildlife conflict as an evolutionary phenomenon may provide insights into how conflict arises and how management plays a critical role in shaping urban wildlife phenotypes

Deferasirox for managing iron overload in people with myelodysplastic syndrome

BACKGROUND: The myelodysplastic syndrome (MDS) comprises a diverse group of haematopoietic stem cell disorders. Due to symptomatic anaemia, most people with MDS require supportive therapy including repeated red blood cell (RBC) transfusions. In combination with increased iron absorption, this contributes to the accumulation of iron resulting in secondary iron overload and the risk of organ dysfunction and reduced life expectancy. Since the human body has no natural means of removing excess iron, iron chelation therapy, i.e. the pharmacological treatment of iron overload, is usually recommended. However, it is unclear whether or not the newer oral chelator deferasirox leads to relevant benefit. OBJECTIVES: To evaluate the effectiveness and safety of oral deferasirox for managing iron overload in people with myelodysplastic syndrome (MDS). SEARCH METHODS: We searched the following databases up to 03 April 2014: MEDLINE, EMBASE, The Cochrane Library, Biosis Previews, Web of Science, Derwent Drug File and four trial registries: Current Controlled Trials (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), ICTRP (www.who.int./ictrp/en/), and German Clinical Trial Register (www.drks.de). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing deferasirox with no therapy, placebo or with another iron-chelating treatment schedule. DATA COLLECTION AND ANALYSIS: We did not identify any trials eligible for inclusion in this review. MAIN RESULTS: No trials met our inclusion criteria. However, we identified three ongoing and one completed trial (published as an abstract only and in insufficient detail to permit us to decide on inclusion) comparing deferasirox with deferoxamine, placebo or no treatment. AUTHORS' CONCLUSIONS: We planned to report evidence from RCTs that evaluated the effectiveness of deferasirox compared to either placebo, no treatment or other chelating regimens, such as deferoxamine, in people with MDS. However, we did not identify any completed RCTs addressing this question.We found three ongoing and one completed RCT (published as an abstract only and in insufficient detail) comparing deferasirox with deferoxamine, placebo or no treatment and data will hopefully be available soon. These results will be important to inform physicians and patients on the advantages and disadvantages of this treatment option

Deferasirox for managing transfusional iron overload in people with sickle cell disease

BACKGROUND: Sickle cell disease (SCD) is a group of genetic haemoglobin disorders, that occurs in about 2.2 per 1000 births worldwide. Increasingly, some people with SCD develop secondary iron overload due to occasional red blood cell transfusions or are on long-term transfusion programmes for e.g. secondary stroke prevention. Iron chelation therapy can prevent long-term complications.Deferoxamine and deferiprone have been found to be efficacious. However, questions exist about the effectiveness and safety of the newer oral chelator deferasirox. OBJECTIVES: To assess the effectiveness and safety of oral deferasirox in people with SCD and secondary iron overload. SEARCH METHODS: We searched the Cystic Fibrosis & Genetic Disorders Group's Haemoglobinopathies Trials Register: date of most recent search:13 March 2014.We searched MEDLINE, Embase, Biosis Previews, Web of Science, Derwent Drug File, XTOXLINE, EBMR and The Cochrane Library, respectively; date of most recent searches: 02 August 2013.We searched four trial registries: www.controlled-trials.com; www.clinicaltrials.gov; www.who.int./ictrp/en/; www.drks.de; date of most recent searches: 03 June 2013. SELECTION CRITERIA: Randomised controlled trials comparing deferasirox with no therapy or placebo or with another iron chelating treatment schedule. DATA COLLECTION AND ANALYSIS: Two authors independently assessed risk of bias and extracted data. We contacted the corresponding study authors for additional information. MAIN RESULTS: Two studies (with 203 and 212 people) comparing the efficacy and safety of deferasirox and deferoxamine after 12 months and 24 weeks, respectively, were included. The overall quality, according to GRADE, for the main outcomes was moderate to low. Only limited data were available on mortality and end-organ damage, although one study did assess mortality, relative risk 1.26 (95% confidence interval 0.05 to 30.41), the 24-week follow up was too short to allow us to draw firm conclusions. One study reported a relative risk of 1.26 for the incidence of type 2 diabetes mellitus (95% confidence interval 0.05 to 30.41). Serum ferritin reduction was significantly greater with deferoxamine, mean difference of change of 440.69 µg/l (95% confidence interval 11.73 to 869.64). Liver iron concentration (reported in one study) measured by superconduction quantum interference device showed no significant difference for the overall group of patients adjusted for transfusion category, mean difference -0.20 mg Fe/g dry weight (95% confidence interval -3.15 to 2.75).The occurrence of serious adverse events did not differ between drugs. Nausea, diarrhoea and rash occurred significantly more often in people treated with deferasirox, while adverse events of any kind were more often reported for patients treated with deferoxamine (one study). The mean increase of creatinine was also significantly higher with deferasirox, mean difference 3.24 (95% confidence interval 0.45 to 6.03). Long-term adverse events could not be measured in the included studies (follow up 52 weeks and 24 weeks). Patient satisfaction and the likelihood of continuing treatment, were significantly better with deferasirox. AUTHORS' CONCLUSIONS: Deferasirox appears to be of similar efficacy to deferoxamine depending on depending on the appropriate ratio of doses of deferoxamine and deferasirox being compared. However, only limited evidence is available assessing the efficacy regarding patient-important outcomes. The short-term safety of deferasirox seems to be acceptable, however, follow up in the available studies was too short to assess long-term side effects. Long-term safety and efficacy data are available from a non-controlled extension phase not included in our review; however, no valid comparative conclusions can be drawn and future studies should assess comparatively long-term outcomes both for safety and efficacy

The evolutionary consequences of human–wildlife conflict in cities

Human–wildlife interactions, including human–wildlife conflict, are increasingly common as expanding urbanization worldwide creates more opportunities for people to encounter wildlife. Wildlife–vehicle collisions, zoonotic disease transmission, property damage, and physical attacks to people or their pets have negative consequences for both people and wildlife, underscoring the need for comprehensive strategies that mitigate and prevent conflict altogether. Management techniques often aim to deter, relocate, or remove individual organisms, all of which may present a significant selective force in both urban and nonurban systems. Management-induced selection may significantly affect the adaptive or nonadaptive evolutionary processes of urban populations, yet few studies explicate the links among conflict, wildlife management, and urban evolution. Moreover, the intensity of conflict management can vary considerably by taxon, public perception, policy, religious and cultural beliefs, and geographic region, which underscores the complexity of developing flexible tools to reduce conflict. Here, we present a cross-disciplinary perspective that integrates human–wildlife conflict, wildlife management, and urban evolution to address how social–ecological processes drive wildlife adaptation in cities. We emphasize that variance in implemented management actions shapes the strength and rate of phenotypic and evolutionary change. We also consider how specific management strategies either promote genetic or plastic changes, and how leveraging those biological inferences could help optimize management actions while minimizing conflict. Investigating human–wildlife conflict as an evolutionary phenomenon may provide insights into how conflict arises and how management plays a critical role in shaping urban wildlife phenotypes

Outcomes of the included methodological research projects.

<p>Outcomes of the included methodological research projects.</p