Search

Literature searches are important components of systematic reviews. They are not only informative of the retrieval process, but they also set the data to be analyzed and influence additional components of systematic reviews. Despite the available guidelines, several studies have shown that the quality of reporting in systematic reviews is deficient in several medical fields. Systematic reviews may not comply completely with those guidelines despite explicitly stating they do. This protocol intends to answer to what extent systematic reviews published in rheumatology journals have complied with the PRISMA's search strategy guidelines published in 2009. The objective of the study is to analyze the compliance with the PRISMA (2009) search strategy guidelines among systematic reviews published in leading rheumatology journals. Inclusion criteria for this umbrella review protocol are systematic reviews (with or without meta-analyses) that mention having followed the PRISMA statement (2009) in their methods section, and published in journals listed in the Rheumatology category of the Journal of Citations Report 2020. Exclusion criteria are articles published before 2009; retraction letters, notes, expressions of concern; systematic reviews using PRISMA 2020. Databases to be consulted are Web of Science, PubMed and Scopus, from inception to present. Data summaries will be presented in graphs, figures, tables and network maps. A narrative synthesis will be described. This protocol complies with guidelines such as PRISMA 2020, PRISMA-A, PRISMA-P, PRISMA-S, PRESS, and JBI Manual for evidence synthesis, as long as it is suitable for umbrella review protocols. Articles in any language will be considered. info:eu-repo/semantics/publishedVersion

The special issue editors selected us to form an "adversarial collaboration" because our publications and teaching encompass both supportive and critical attitudes toward the Rorschach and its recently developed system for use, the Rorschach Performance Assessment System (R-PAS). We reviewed the research literature and case law to determine if the Rorschach and specifically R-PAS meet legal standards for admissibility in court. We included evidence on norms, reliability, validity, utility, general acceptance, forensic evaluator use, and response style assessment, as well as United States and selected European case law addressing challenges to mental examination motions, admissibility, and weight. Compared to other psychological tests, the Rorschach is not challenged at unusually high rates. Although the recently introduced R-PAS is not widely referenced in case law, evidence suggests that information from it is likely to be ruled admissible when used by a competent evaluator and selected variables yield scores that are sufficiently reliable and valid to evaluate psychological processes that inform functional psycholegal capacities. We identify effective and ethical but also inappropriate uses (e.g., psychological profiling) of R-PAS in criminal, civil, juvenile, and family court. We recommend specific research to clarify important aspects of R-PAS and advance its utility in forensic mental health assessment.

The special issue editors selected us to form an "adversarial collaboration" because our publications and teaching encompass both supportive and critical attitudes toward the Rorschach and its recently developed system for use, the Rorschach Performance Assessment System (R-PAS). We reviewed the research literature and case law to determine if the Rorschach and specifically R-PAS meet legal standards for admissibility in court. We included evidence on norms, reliability, validity, utility, general acceptance, forensic evaluator use, and response style assessment, as well as United States and selected European case law addressing challenges to mental examination motions, admissibility, and weight. Compared to other psychological tests, the Rorschach is not challenged at unusually high rates. Although the recently introduced R-PAS is not widely referenced in case law, evidence suggests that information from it is likely to be ruled admissible when used by a competent evaluator and selected variables yield scores that are sufficiently reliable and valid to evaluate psychological processes that inform functional psycholegal capacities. We identify effective and ethical but also inappropriate uses (e.g., psychological profiling) of R-PAS in criminal, civil, juvenile, and family court. We recommend specific research to clarify important aspects of R-PAS and advance its utility in forensic mental health assessment.

Background The gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with Faecalibacterium prausnitizii associated with protection, and certain genera (including Shigella and Escherichia) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype. Aims To evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota. Methods We conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included. Results We screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α-diversity was observed in responders versus non-responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline Faecalibacterium predicted response to infliximab and ustekinumab. A post-treatment increase in Faecalibacterium prausnitzii was noted in responders to aminosalicylates, anti-TNF medications and ustekinumab; conversely, this species decreased in responders to EEN. Escherichia was a consistent marker of unfavourable drug response, and its presence in the gut mucosa correlated with inflammation in aminosalicylate-treated patients. Conclusions Both gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments.

Objectives At the end of 2019, an acute infectious pneumonia (coronavirus disease 2019 [COVID-19]) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, and subsequently spread around the world starting a pandemic. Globally, to date, there have been >118 million confirmed cases, including >2 million deaths. In this context, it has been shown that the psychological impact of the pandemic is important and that it can be associated with an increase in internet searches related to fear, anxiety, depression, as well as protective behaviours, health knowledge and even maladaptive behaviours. Study design This is a systematic review. Methods This review aims to collect, analyse and synthesise available evidence on novel data streams for surveillance purposes and/or their potential for capturing the public reaction to epidemic outbreaks, particularly focusing on mental health effects and emotions. Results At the end of the screening process, 19 articles were included in this systematic review. Our results show that the COVID-19 pandemic had a great impact on internet searches for mental health of entire populations, which manifests itself in a significant increase of depressed, anxious and stressed internet users’ emotions. Conclusions Novel data streams can support public health experts and policymakers in establishing priorities and setting up long-term strategies to mitigate symptoms and tackle mental health disorders., Graphical abstract Image 1

Objectives: At the end of 2019, an acute infectious pneumonia (coronavirus disease 2019 [COVID-19]) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Wuhan, China, and subsequently spread around the world starting a pandemic. Globally, to date, there have been >118 million confirmed cases, including >2 million deaths. In this context, it has been shown that the psychological impact of the pandemic is important and that it can be associated with an increase in internet searches related to fear, anxiety, depression, as well as protective behaviours, health knowledge and even maladaptive behaviours.Study design: This is a systematic review.Methods: This review aims to collect, analyse and synthesise available evidence on novel data streams for surveillance purposes and/or their potential for capturing the public reaction to epidemic outbreaks, particularly focusing on mental health effects and emotions.Results: At the end of the screening process, 19 articles were included in this systematic review. Our results show that the COVID-19 pandemic had a great impact on internet searches for mental health of entire populations, which manifests itself in a significant increase of depressed, anxious and stressed internet users' emotions.Conclusions: Novel data streams can support public health experts and policymakers in establishing priorities and setting up long-term strategies to mitigate symptoms and tackle mental health disorders. (C) 2021 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Funder: Arcus Foundation; Id: http://dx.doi.org/10.13039/100016681, Funder: Darwin Initiative, Funder: European Association of Zoos and Aquaria; Id: http://dx.doi.org/10.13039/501100009167, Funder: European Outdoor Conservation Association; Id: http://dx.doi.org/10.13039/501100013711, Funder: Fundacion Bioparc, Funder: Ocean Parks Conservation Foundation Hong Kong, Funder: Orangutan Land Trust, Funder: Save the Orangutan, Funder: Taronga Zoo, Funder: The Orangutan Project, Funder: Ministry of Environment & Forestry, Funder: PT Rimba Makmur Utama, Degraded tropical peatlands lack tree cover and are often subject to seasonal flooding and repeated burning. These harsh environments for tree seedlings to survive and grow are therefore challenging to revegetate. Knowledge on species performance from previous plantings represents an important evidence base to help guide future tropical peat swamp forest (TPSF) restoration efforts. We conducted a systematic review of the survival and growth of tree species planted in degraded peatlands across Southeast Asia to examine (1) species differences, (2) the impact of seedling and site treatments on survival and growth and (3) the potential use of plant functional traits to predict seedling survival and growth rates. Planted seedling monitoring data were compiled through a systematic review of journal articles, conference proceedings, reports, theses and unpublished datasets. In total, 94 study‐sites were included, spanning three decades from 1988 to 2019, and including 141 indigenous peatland tree and palm species. Accounting for variable planting numbers and monitoring durations, we analysed three measures of survival and growth: (1) final survival weighted by the number of seedlings planted, (2) half‐life, that is, duration until 50% mortality and (3) relative growth rates (RGR) corrected for initial planting height of seedlings. Average final survival was 62% and half‐life was 33 months across all species, sites and treatments. Species differed significantly in survival and half‐life. Seedling and site treatments had small effects with the strongest being higher survival of mycorrhizal fungi inoculated seedlings; lower survival, half‐life and RGR when shading seedlings; and lower RGR and higher survival when fertilising seedlings. Leaf nutrient and wood density traits predicted TPSF species survival, but not half‐life and RGR. RGR and half‐life were negatively correlated, meaning that slower growing species survived for longer. Synthesis and applications. To advance tropical peat swamp reforestation requires expanding the number and replication of species planted and testing treatments by adopting control vs. treatment experimental designs. Species selection should involve slower growing species (e.g. Lophopetalum rigidum, Alstonia spatulata, Madhuca motleyana) that survive for longer and explore screening species based on functional traits associated with nutrient acquisition, flooding tolerance and recovery from fire.

Objectives: We aimed to assess whether limiting the inclusion criteria solely to English-language publications affected the overall conclusions of evidence syntheses.Study Design and Setting: Our analyses used a dataset of a previous methods study that included 59 randomly selected Cochrane intervention reviews with no language restrictions. First, we ascertained the publication language of all 2,026 included publications. Next, we excluded studies based on the following criteria: (1) publication solely in non-English language, or (2) main publication (in case of multiple publications of the same study) in non-English language. We then re-calculated meta-analyses for outcomes that were presented in the main summary of findings tables of the Cochrane reports. If the direction of the effect estimate or the statistical significance changed, authors of the respective Cochrane reviews were consulted to assess whether the new evidence base would have changed their conclusions. The primary outcome of our analyses examined the proportion of conclusions that would change with the exclusion of non-English publications. We set the threshold for the approach as noninferior if the upper limit of the 95% confidence interval of the proportion of changed conclusions did not cross a margin of 10%.Results: Across all 59 Cochrane reviews, 29 (49%) included 80 non-English publications. For 16 (27%) of these Cochrane reviews, the exclusion of non-English publications resulted in the exclusion of at least one study. In the remaining 13 Cochrane reviews, the non-English publications were not the only or main publication of the study or they did not contribute to the main summary of the findings table, so their exclusion did not result in an exclusion of the study.Overall, the exclusion of non-English publications led to the exclusion of 31 studies contributing to 40 outcomes. For 38 of the 40 outcomes, the exclusion of non-English studies did not markedly alter the size or direction of effect estimates or statistical significance. In two outcomes, the statistical significance changed, but authors would have still drawn the same conclusion, albeit with less certainty. Thus, the proportion of changed conclusions in our sample was 0.0% (95% CI 0.0-0.6), which indicated the noninferiority of the approach. However, the majority of excluded studies were small.Conclusion: Exclusion of non-English publications from systematic reviews on clinical interventions had a minimal effect on overall conclusions and could be a viable methodological shortcut, especially for rapid reviews. (C) 2019 Elsevier Inc. All rights reserved.

Purpose To compare the differences in lifestyle behaviours between cancer survivors (CSs) and cancer-free participants in a large and representative population-based cohort. Methods We included 115,257 adults from the Lifelines cohort. Cancer status was self-reported, and health behaviours were measured (e.g. body mass index [BMI]) or assessed by questionnaire (e.g. physical activity, smoking, alcohol consumption, sedentary behaviour and diet). The data were then categorised for logistic regression analysis, stratified and adjusted by sex and age ( Results CSs (5473; 4.7%) were diagnosed 9 ± 8.5 years before data collection, were older (mean age 55.4 vs 44.4 years) and more often female (66.6% vs 33.4%) than the cancer-free participants. They were also more likely to be physically active and to have a better diet, and also less likely to be alcohol drinkers; but, were more likely to have a higher BMI, be former smokers and to be sedentary. After adjustment for sex and age, however, BMI was more likely to be normal, physical activity was more likely to be higher and smoking to be prevalent in CSs. Current smoking was also significantly higher among females and those aged Conclusions In this population-based cohort, CSs have health behaviour comparable to those without a cancer diagnosis. Implications for cancer survivors Smoking cessation strategies should target all CSs, but efforts could yield greatest benefit if they target females and those younger than 55 years.

Background Currently, five biologic treatment options are available for use in patients with uncontrolled persistent asthma: three interleukin (IL)-5 antagonists, which either bind to the anti-IL-5 ligand (mepolizumab, reslizumab) or to the IL-5 receptor (benralizumab); one anti-immunoglobulin E (anti-IgE) therapy (omalizumab); and one anti-IL-4/IL-13 therapy (dupilumab). To date, no comparative data from head-to-head clinical trials are available for these biologics. Objective An indirect treatment comparison (ITC) of dupilumab versus each of the anti-IL-5 and anti-IgE therapies using the endpoints of annualized severe asthma exacerbation rates and change in pre-bronchodilator forced expiratory volume in 1 s (FEV1). Methods Embase®, MEDLINE®, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for studies published between January 1, 1980 and March 25, 2019. Eligible articles included randomized controlled trials (RCTs) in patients aged ≥ 12 years with persistent/uncontrolled asthma using at least medium-to-high dose inhaled corticosteroid plus long-acting β2-agonist with add-on biologic therapy. Bucher ITCs were performed to compare subgroups of dupilumab patients with the anti-IL-5s and anti-IgE trial populations. Results Fourteen RCTs were included in the analyses. The matched dupilumab subgroups were associated with greater reductions in annualized severe exacerbation rates compared with benralizumab, mepolizumab, reslizumab, and omalizumab (54%, 28%, 38%, and 26% greater reduction, respectively). A greater improvement in FEV1 was also observed for dupilumab at week 12 and/or week 24/52 than for the other biologics (0.06–0.14 L). Conclusion In this ITC, dupilumab was associated with lower severe asthma exacerbation rates and greater improvements in lung function than anti-IL-5s and omalizumab.

AimEarlier research has revealed a strong relationship between alcohol use and sickness absence. The aim of this review was to explore and uncover this relationship by looking at differences in type of design (cross-sectional vs. longitudinal), type of data (self-reported vs. registered data), and type of sickness absence (long-term vs. short term).MethodSix databases were searched through June 2020. Observational and experimental studies from 1980 to 2020, in English or Scandinavian languages reporting the results of the association between alcohol consumption and sickness absence among working population were included. Quality assessment, and statistical analysis focusing on differences in the likelihood of sickness absence on subgroup levels were performed on each association, not on each study. Differences in the likelihood of sickness absence were analyzed by means of meta-analysis. PROSPERO registration number: CRD42018112078.ResultsFifty-nine studies (58% longitudinal) including 439,209 employees (min. 43, max. 77,746) from 15 countries were included. Most associations indicating positive and statistically significant results were based on longitudinal data (70%) and confirmed the strong/causal relationship between alcohol use and sickness absence. The meta-analysis included eight studies (ten samples). The increased risk for sickness absence was likely to be found in cross-sectional studies (OR: 8.28, 95% CI: 6.33–10.81), studies using self-reported absence data (OR: 5.16, 95% CI: 3.16–8.45), and those reporting short-term sickness absence (OR: 4.84, 95% CI: 2.73–8.60).ConclusionThis review supports, but also challenges earlier evidence on the association between alcohol use and sickness absence. Certain types of design, data, and types of sickness absence may produce large effects. Hence, to investigate the actual association between alcohol and sickness absence, research should produce and review longitudinal designed studies using registry data and do subgroup analyses that cover and explain variability of this association.

IntroductionConsidering the rising global healthcare expenses, economic evaluations are more important than ever. Even though the number of studies regarding costs and cost-effectiveness is increasing, the quality of these studies remains relatively low. This is mainly caused by abundant heterogeneity in methods used for determining, calculating and reporting cost data, despite current general guidelines for the conduct of economic evaluations. Disease-specific recommendations for the conduct of economic evaluations in the field of spine surgery, as complement to existing general guidelines, will ameliorate overall research quality, comparability and interpretability and thus, the overall quality. We aim to provide expert-based recommendations for the design, conduct, and reporting of economic evaluations in spine surgery.Methods and analysisA modified Delphi study will be conducted to formulate expert-based recommendations. The following steps will be taken:(1) The conduct of a systematic review to identify relevant publications and identify relevant authors. Formation of an expert group and a Delphi-panel. (2) Drafting of statements based on articles included in the systematic literature review. Validation of drafted statements by the expert group. Step 2 can be repeated up to three times, statements can be discarded and adjusted in these rounds. Statements with more than 75% agreement will be accepted as consensus statements. (3) Validation of statements by the Delphi-panel. (4) Final recommendations.Ethics and disseminationThe underlying work is based on existing literature and published data and does not include participation of patients, and thus does not require ethical review approval. The final recommendations are intended for (clinical) researchers in the field of cost-effectiveness in spine surgery. The Delphi method ensures that the final output reflects the opinions of international participants and gives insight in the adherence level to the recommendations. The aim is to reach uniformity in design, conduct and reporting of these studies, as is currently lacking. This will provide a solid basis to determine cost-effectiveness of spine surgeries and consequently aid to limit the rising healthcare costs. The findings of this study and the final recommendations will be disseminated in conferences and seminars and will be published in an international peer-reviewed journal.

Literature searches are important components of systematic reviews. They are not only informative of the retrieval process, but they also set the data to be analyzed and influence additional components of systematic reviews. Despite the available guidelines, several studies have shown that the quality of reporting in systematic reviews is deficient in several medical fields. Systematic reviews may not comply completely with those guidelines despite explicitly stating they do. This protocol intends to answer to what extent systematic reviews published in rheumatology journals have complied with the PRISMA's search strategy guidelines published in 2009. The objective of the study is to analyze the compliance with the PRISMA (2009) search strategy guidelines among systematic reviews published in leading rheumatology journals. Inclusion criteria for this umbrella review protocol are systematic reviews (with or without meta-analyses) that mention having followed the PRISMA statement (2009) in their methods section, and published in journals listed in the Rheumatology category of the Journal of Citations Report 2020. Exclusion criteria are articles published before 2009; retraction letters, notes, expressions of concern; systematic reviews using PRISMA 2020. Databases to be consulted are Web of Science, PubMed and Scopus, from inception to present. Data summaries will be presented in graphs, figures, tables and network maps. A narrative synthesis will be described. This protocol complies with guidelines such as PRISMA 2020, PRISMA-A, PRISMA-P, PRISMA-S, PRESS, and JBI Manual for evidence synthesis, as long as it is suitable for umbrella review protocols. Articles in any language will be considered.

In recent years, the research on human behaviour in relation to waste management has increased at an expo-nential rate. At the same time, the expanding academic literature on this topic makes it more difficult to un-derstand the main areas of interest, the leading institutions and authors, the possible interconnections among different disciplines, and the gaps. This paper maps knowledge domain on recycling behaviour through biblio-metric analysis and text mining in order to identify current trends, research networks and hot topics. 2061 ar-ticles between 1975 and 2020 from three different databases are examined with an interdisciplinary approach. The findings reveal that 60% of papers have been published between 2015 and 2020, and this topic is of global interest. Leading countries are mainly located in Europe, North America and Commonwealth; however, China and Malaysia are also assuming a driving role. Bibliometrics and text mining provide the intellectual configu-ration of the knowledge on recycling behaviour; co-word analysis individuates conceptual sub-domains in food waste, determinants of recycling behaviour, waste management system, waste electrical and electronic equip-ment (WEEE), higher-level education, plastic bags, and local government. Overall, waste management and related human behaviour represent a universal challenge requiring a structured and interdisciplinary approach at all levels (individual, institutions, industry, academia). Lastly, this paper offers some suggestions for future research such as smart city design, sensor network system, consumer responsibilisation, the adoption of a more comprehensive view of the areas of investigation through the holistic analysis of all stakeholders.

This review aimed to identify the behavioral change techniques (BCTs) used in behavioral interventions for tobacco cessation at dental practices in relation to their effect on tobacco use. Six scientific databases were searched for behavior change interventions for tobacco cessation and were coded using the BCT taxonomy of behavioral support for smoking cessation (BCTTsm). Fifteen interventions were identified, and data related to intervention characteristics were abstracted. Sixteen BCTs were identified, mainly related to increased motivation and teaching regulatory skills. Goal setting was the most commonly used BCT. Ten out of fifteen interventions effectively impacted tobacco cessation outcomes (OR = 2 to 5.25). Effective interventions more frequently included goal setting, written materials, readiness to quit and ability assessment, tobacco-use assessment, self-efficacy boost, listing reasons for quitting, action planning and environment restructuring. Other BCTs were not clearly associated with an increased effect. Among the behavioral interventions, certain techniques were associated with successful tobacco quitting. Tobacco cessation interventions in a dental setting appear to benefit from using BCTs that increase motivation and teach regulatory skills. The identified BCTs in this review could provide a source to better inform researchers and dentists about the active ingredients in behavior change interventions for tobacco cessation in a dental setting.

This review aimed to identify the behavioral change techniques (BCTs) used in behavioral interventions for tobacco cessation at dental practices in relation to their effect on tobacco use. Six scientific databases were searched for behavior change interventions for tobacco cessation and were coded using the BCT taxonomy of behavioral support for smoking cessation (BCTTsm). Fifteen interventions were identified, and data related to intervention characteristics were abstracted. Sixteen BCTs were identified, mainly related to increased motivation and teaching regulatory skills. Goal setting was the most commonly used BCT. Ten out of fifteen interventions effectively impacted tobacco cessation outcomes (OR = 2 to 5.25). Effective interventions more frequently included goal setting, written materials, readiness to quit and ability assessment, tobacco-use assessment, self-efficacy boost, listing reasons for quitting, action planning and environment restructuring. Other BCTs were not clearly associated with an increased effect. Among the behavioral interventions, certain techniques were associated with successful tobacco quitting. Tobacco cessation interventions in a dental setting appear to benefit from using BCTs that increase motivation and teach regulatory skills. The identified BCTs in this review could provide a source to better inform researchers and dentists about the active ingredients in behavior change interventions for tobacco cessation in a dental setting.

Background Poor cognitive performance is associated with high vascular risk. However, this association is only investigated in elderly. As neuropathological changes precede clinical symptoms of cognitive impairment by several decades, it is likely that cognitive performance is already associated with vascular risk at middle-age. Objectives To investigate the association of cognitive performance with treatable vascular risk in middle-aged and old persons. Design Longitudinal study with three measurements during follow-up period of 5.5 years. Setting City of Groningen, the Netherlands. Participants Cohort of 3,572 participants (age range, 35–82 years; mean age, 54 years; men, 52%). Exposure Treatable vascular risk as defined by treatable components of the Framingham Risk Score for Cardiovascular Disease at the first measurement (diabetes mellitus, smoking, hypercholesterolemia and hypertension). Measurements Change in cognitive performance during follow-up. Cognitive performance was measured with Ruff Figural Fluency Test (RFFT) and Visual Association Test (VAT), and calculated as the average of the standardized RFFT and VAT score per participant. Results The mean (SD) cognitive performance changed from 0.00 (0.79) at the first measurement to 0.15 (0.83) at second measurement and to 0.39 (0.82) at the third measurement (Ptrend

Cancer incidence is rising, and accurate prediction of incident cancers could be relevant to understanding and reducing cancer incidence. The aim of this study was to develop machine learning (ML) models that could predict an incident diagnosis of cancer. Participants without any history of cancer within the Lifelines population-based cohort were followed for a median of 7 years. Data were available for 116,188 cancer-free participants and 4232 incident cancer cases. At baseline, socioeconomic, lifestyle, and clinical variables were assessed. The main outcome was an incident cancer during follow-up (excluding skin cancer), based on linkage with the national pathology registry. The performance of three ML algorithms was evaluated using supervised binary classification to identify incident cancers among participants. Elastic net regularization and Gini index were used for variables selection. An overall area under the receiver operator curve (AUC) &lt, 0.75 was obtained, the highest AUC value was for prostate cancer (random forest AUC = 0.82 (95% CI 0.77–0.87), logistic regression AUC = 0.81 (95% CI 0.76–0.86), and support vector machines AUC = 0.83 (95% CI 0.78–0.88), respectively), age was the most important predictor in these models. Linear and non-linear ML algorithms including socioeconomic, lifestyle, and clinical variables produced a moderate predictive performance of incident cancers in the Lifelines cohort.

Introduction The demand for spinal fusion surgery has increased over the last decades. Health care providers should take costs and cost-effectiveness of these surgeries into account. Open transforaminal lumbar interbody fusion (TLIF) and posterior lumbar interbody fusion (PLIF) are two widely used techniques for spinal fusion. Earlier research revealed that TLIF is associated with less blood loss, shorter surgical time and sometimes shorter length of hospital stay, while effectiveness of both techniques on back and/or leg pain are equal. Therefore, TLIF could result in lower costs and be more cost-effective than PLIF. This is the first systematic review comparing direct and indirect (partial) economic evaluations of TLIF with PLIF in adults with lumbar spondylolisthesis. Furthermore, methodological quality of included studies was assessed. Methods Searches were conducted in eight databases for reporting on eligibility criteria; TLIF or PLIF, lumbar spondylolisthesis or lumbar instability, and cost. Costs were converted to United States Dollars with reference year 2020. Study quality was assessed using the bias assessment tool of the Cochrane Handbook for Systematic Reviews of Interventions, the Level of Evidence guidelines of the Oxford Centre for Evidence-based Medicine and the Consensus Health Economic Criteria (CHEC) list. Results Of a total of 693 studies, 16 studies were included. Comparison of TLIF and PLIF could only be made indirectly, since no study compared TLIF and PLIF directly. There was a large heterogeneity in health care and societal perspective costs due to different in-, and exclusion criteria, baseline characteristics and the use of costs or charges in calculations. Health care perspective costs, calculated with hospital costs, ranged from $15,867-$43,217 in TLIF-studies and $32,662 in one PLIF-study. Calculated with hospital charges, it ranged from $8,964-$51,469 in TLIF-studies and $21,838-$93,609 in two PLIF-studies. Societal perspective costs and cost-effectiveness, only mentioned in TLIF-studies, ranged from $5,702/QALY-$48,538/QALY and $50,092/QALY-$90,977/QALY, respectively. Overall quality of studies was low. Conclusions This systematic review shows that TLIF and PLIF are expensive techniques. Moreover, firm conclusions about the preferable technique, based on (partial) economic evaluations, cannot be drawn due to limited studies and heterogeneity. Randomized prospective trials and full economical evaluations with direct TLIF and PLIF comparison are needed to obtain high levels of evidence. Furthermore, development of guidelines to perform adequate economic evaluations, specified for the field of interest, will be useful to minimize heterogeneity and maximize transferability of results. Trial registration Prospero-database registration number: CRD42020196869.

[Objectives] Chronic diseases are the leading cause of disability globally. Most chronic disease management occurs in primary care with outcomes varying across primary care providers. Computerised clinical decision support systems (CDSS) have been shown to positively affect clinician behaviour by improving adherence to clinical guidelines. This study provides a summary of the available evidence on the effect of CDSS embedded in electronic health records on patient-reported and clinical outcomes of adult patients with chronic disease managed in primary care., [Design and eligibility criteria] Systematic review, including randomised controlled trials (RCTs), cluster RCTs, quasi-RCTs, interrupted time series and controlled before-and-after studies, assessing the effect of CDSS (vs usual care) on patient-reported or clinical outcomes of adult patients with selected common chronic diseases (asthma, chronic obstructive pulmonary disease, heart failure, myocardial ischaemia, hypertension, diabetes mellitus, hyperlipidaemia, arthritis and osteoporosis) managed in primary care., [Data sources] Medline, Embase, CENTRAL, Scopus, Health Management Information Consortium and trial register clinicaltrials.gov were searched from inception to 24 June 2020., [Data extraction and synthesis] Screening, data extraction and quality assessment were performed by two reviewers independently. The Cochrane risk of bias tool was used for quality appraisal., [Results] From 5430 articles, 8 studies met the inclusion criteria. Studies were heterogeneous in population characteristics, intervention components and outcome measurements and focused on diabetes, asthma, hyperlipidaemia and hypertension. Most outcomes were clinical with one study reporting on patient-reported outcomes. Quality of the evidence was impacted by methodological biases of studies., [Conclusions] There is inconclusive evidence in support of CDSS. A firm inference on the intervention effect was not possible due to methodological biases and study heterogeneity. Further research is needed to provide evidence on the intervention effect and the interplay between healthcare setting features, CDSS characteristics and implementation processes., [PROSPERO registration number] CRD42020218184.

Introduction Polyunsaturated n-3 fatty acid preparations containing eicosapentaenoic acid (EPA) and docosahexanaenoic acid (DHA), or EPA only, have long been recommended in the management of hypertriglyceridaemia, especially when severe (triglyceride levels ≥500 mg/dL), at the dose of 2-4 g/d, mostly for the prevention of acute pancreatitis. Material and methods The presented article reviews clinical trials and their metaanalyses which evaluated the effect of n-3 fatty acids on cardiovascular disease risk, and regulatory agencies' and cardiac societies' positions regarding their use. Results The findings indicate that only EPA is effective. Particular clinical benefit (25% reduction of cardiovascular events) was observed in the recently published REDUCE-IT trial which evaluated EPA (icosapent ethyl) at the dose of 4 g/d for 4.9 years (median), compared to placebo, in hypertriglycerydaemic patients at high or very high cardiovascular risk. This positive effect has been reflected in the expert opinions which recommend eicosapent ethyl (4 g/d) in patients similar to those participating in the REDUCE-IT trial. Additional data in favour of the above position have been provided by the EVAPORATE trial results which showed reduced progression of coronary atherosclerosis with EPA at the dose of 4 g/d. Conclusions The clinical studies and metaanalyses strongly point out that only EPA (icosapent ethyl), especially at dose of 4 g/d, is effective in reducing cardiovascular events in very high and high risk patients with hypertriglyceridemia. The use of EPA + DHA preparations in doses up to 1 g/d does not prevent recurrent cardiovascular events.

This study examined test-retest reliabilities and (predictors of) practice effects of the widely used computerized neuropsychological battery CNS Vital Signs. The sample consisted of 158 Dutch healthy adults. At 3 and 12 months follow-up, 131 and 77 participants were retested. Results revealed low to high test-retest reliability coefficients for CNS VS' test and domain scores. Participants scored significantly higher on the domains of Cognitive Flexibility, Processing Speed, and Reaction Time at the 3-month retest. No significant differences in performance were found over the second interval. Age, education, and retest-interval were not significantly associated with practice effects. These results highlight the need for methods that evaluate performance over time while accounting for imperfect test-retest reliabilities and practice effects. We provided RCI-formulae for determining reliable change, which may be possible solution for future work facing the methodological issues of retesting.Public Significance StatementImperfect test-retest reliability and practice effects must be taken into account when interpreting change in neuropsychological test scores over time, for example by applying RCI-formulae for the determination of reliable change.

BACKGROUND: In previous studies, correlation between overall survival (OS) and surrogate endpoints like objective response rate (ORR) or progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) was poor. This can be biased by crossover and postprogression treatments.OBJECTIVES: To evaluate the relationship between these two surrogate endpoints and OS in advanced NSCLC studies that did not allow for crossover or reported balanced post-progression treatments.METHODS: A systematic review in patients with advanced NSCLC receiving second- and further-line therapy was performed. The relationship between the absolute difference in ORR or median PFS (mPFS) and the absolute difference in median OS (mOS) was assessed using the correlation coefficient (R) and weighted regression models. The analysis was repeated in predefined data cuts based on crossover and balance of postprogression treatments. When the upper limit of R's 95% confidence interval (CI) was more than 0.7, the surrogate threshold effect (STE) was estimated.RESULTS: In total, 146 randomized clinical trials (43,061 patients) were included. The mean ORR, mPFS, and mOS were 12.2% ± 11.2%, 3.2 ± 1.3 months, and 9.6 ± 4.1 months, respectively. The correlation coefficients of ORR and mPFS were 0.181 (95% CI 0.016-0.337) and 0.254 (95% CI 0.074-0.418), respectively, with mOS. Nevertheless, in trials that did not allow crossover and reported balanced postprogression treatments, the correlation coefficients of ORR and mPFS were 0.528 (95% CI 0.081-0.798) and 0.778 (95% CI 0.475-0.916), respectively, with mOS. On the basis of STE estimation, in trials showing significant treatment effect size of 41.0% or more ORR or 4.15 or more mPFS months, OS benefit can be expected with sufficient certainty.CONCLUSIONS: Crossover and postprogression treatments may bias the relationship between surrogate endpoints and OS. Presented STE calculation can be used to interpret treatment effect on either ORR or PFS when used as primary endpoints.

BACKGROUNDStorage time of platelet (PLT) concentrates has been negatively associated with clinical efficacy outcomes. The aim of this study was to quantify the association between storage time of PLT concentrates and interval to the next PLT transfusion for different types of PLT components, stored for up to 7 days and transfused to transfusion-dependent hematooncology patients with thrombocytopenia. STUDY DESIGN AND METHODSFrom a cohort of patients from 10 major Dutch hospitals, patients were selected whose transfusion patterns were compatible with PLT transfusion dependency due to hematooncologic disease. Mean time to the next transfusion and mean differences in time to the next transfusion for different storage time categories (i.e., fresh, 5 days) were estimated, per component type, using multilevel mixed-effects linear models. RESULTSAmong a cohort of 29,761 patients who received 140,896 PLT transfusions we selected 4441 hematooncology patients who had received 12,724 PLT transfusions during periods of PLT transfusion dependency. Transfusion of fresh, compared to old, buffy coat-derived PLTs in plasma was associated with a delay to the next transfusion of 6.2 hours (95% confidence interval [CI], 4.5-8.0 hr). For buffy coat-derived PLTs in PAS-B and -C this difference was 7.7 hours (95% CI, 2.2-13.3 hr) and 3.9 hours (95% CI, -2.1 to 9.9 hr) while for apheresis PLTs in plasma it was only 1.8 hours (95% CI, -3.5 to 7.1 hr). CONCLUSIONOur results indicate that the time to the next transfusion shortens with increasing age of transfused buffy coat-derived PLT concentrates. This association was not observed for apheresis PLTs.

Purpose: The aim of this study was to critically review the current evidence regarding the oncologic outcomes after laparoscopic converted or open resection for colorectal cancer.Materials and Methods: A literature search was performed in Pubmed. Study selection and data acquisition were independently performed by 2 reviewers.Results: The search strategy yielded a total of 746 articles, resulting in 7 studies eligible for inclusion. A total of 9190 (57 to 8307) patients were included in the open and 238 (17 to 56) in the converted group. In none of the studies, differences were found in disease stage between both groups. There were no significant differences between both groups with regard to overall survival, local recurrence and distant metastasis rate.Conclusions: There is currently insufficient evidence that patients who had a laparoscopic resection for colorectal cancer converted to open surgery have a worse oncologic outcome than patients who were primarily treated by an open approach.

Purpose The aim of this study was to critically review the current evidence regarding the oncologic outcomes after laparoscopic converted or open resection for colorectal cancer. Materials and methods A literature search was performed in Pubmed. Study selection and data acquisition were independently performed by 2 reviewers. Results The search strategy yielded a total of 746 articles, resulting in 7 studies eligible for inclusion. A total of 9190 (57 to 8307) patients were included in the open and 238 (17 to 56) in the converted group. In none of the studies, differences were found in disease stage between both groups. There were no significant differences between both groups with regard to overall survival, local recurrence and distant metastasis rate. Conclusions There is currently insufficient evidence that patients who had a laparoscopic resection for colorectal cancer converted to open surgery have a worse oncologic outcome than patients who were primarily treated by an open approach.

AIMS: To summarize the best available evidence on the effectiveness of physical counterpressure manoeuvers (PCM) for vasovagal syncope management compared to a control intervention. Control interventions included either a PCM, no intervention, or other interventions feasible in a lay setting. METHODS: A systematic literature search (March 21st 2018) was performed in the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase. PCM were subdivided into 1) PCM decreasing orthostatic load (PCMOL), 2) PCM shortening the hydrostatic column between heart and brain (PCMHC), 3) PCM using mechanical compression of the veins (PCMMC). The primary outcome was syncope, secondary outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR). When possible, a random effects meta-analysis was performed. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for dichotomous outcomes, and mean differences (MD) or standardized mean differences (SMD) were calculated for continuous outcomes. Heterogeneity was assessed by means of the I2 statistic. The total body of evidence was evaluated by means of the GRADE methodology. RESULTS: Eleven trials involving 688 people with vasovagal syncope were included. Risk of bias was high in all included studies. The total body of evidence (GRADE) was considered to be low or very low. PCM were found to improve syncope as compared to control (OR: 0.52, 95% CI [0.33;0.81], p = 0.004). Similarly, before-and-after studies without a control group showed a significant reduction in syncope following PCM (OR: 0.01, 95%CI [0.00;0.01], p

Non-syndromic cleft lip with or without cleft palate (nsCL/P) ranks among the most common human congenital malformations, and has a multifactorial background in which both exogenous and genetic risk factors act in concert. The present report describes a genome-wide association study (GWAS) involving a total of 285 nsCL/P patients and 1212 controls from the Netherlands and Belgium. Twenty of the 40 previously reported nsC/LP susceptibility loci were replicated, which underlined the validity of this sample. SNV-based analysis of the data identified an as yet unreported suggestive locus at chromosome 16p12.1 (p-value of the lead SNV: 4.17 &times, 10&minus, 7). This association was replicated in two of three patient/control replication series (Central European and Yemeni). Gene analysis of the GWAS data prioritized SH3PXD2A at chromosome 10q24.33 as a candidate gene for nsCL/P. To date, support for this gene as a cleft gene has been restricted to data from zebrafish and a knockout mouse model. The present GWAS was the first to implicate SH3PXD2A in non-syndromic cleft formation in humans. In summary, although performed in a relatively small sample, the present GWAS generated novel insights into nsCL/P etiology.

Agradecimentos: The authors would like to thank for the support received from São Paulo Research Foundation (FAPESP) Abstract: This study evaluated the degree of conversion and mechanical properties of experimental composite resins made with different fillers and light-curing methods. All composites had the same organic matrix (40% wt) and photoinitiator system (1.2% wt). Experimental composite groups were divided according to ratio (%) of silanated ground glass (0.5 µm) (BaAlSi) and fumed silica (SiO2): 100/0, 90/10, 80/20, and 70/30. Light-emitting diode light was used in the continuous, soft-start, and pulse-delay modes (n = 10). Degree of conversion was determined using attenuated total reflectance-Fourier transform infrared spectroscopy. Flexural strength and modulus were obtained using a universal testing machine, and Knoop microhardness was measured in a Knoop indenter. The data were subjected to a two-way ANOVA and Tukey's post hoc test (a = 0.05). Continuous-light exposure of the 100/0 group produced the highest degrees of conversion. Soft-start exposure of the 70/30 groups produced the highest Knoop microhardness. The pulse-delay method produced the lowest flexural strength and modulus values. The 100/0 and 70/30 groups had the lowest flexural strength and flexural modulus, respectively. Application of continuous-light output with composite resins containing a ratio of 80/20 (BaAlSi/SiO2) fillers generated the best results regarding the degree of conversion and mechanical properties FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP Fechado

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Intermittent auscultation (IA) is the technique of listening to and counting the fetal heart rate (FHR) for short periods during active labour and continuous cardiotocography (CTC) implies FHR monitoring for longer periods. Although the evidence suggests that IA is the best way to monitor healthy women at low risk of complications, there is no scientific evidence for the ideal device, timing, frequency and duration for IA. We aimed to give an overview of the field, identify and describe methods and practices for performing IA, map the evidence and accuracy for different methods of IA, and identify research gaps. Methods We conducted a systematic scoping review following the Joanna Briggs methodology. Medline, EMBASE, Cinahl, Maternity & Infant Care, Cochrane Library, SveMed+, Web of Science, Scopus, Lilacs and African Journals Online were searched for publications up to January 2019. We did hand searches in relevant articles and databases. Studies from all countries, international guidelines and national guidelines from Denmark, United Kingdom, United States, New Zealand, Australia, The Netherlands, Sweden, Denmark, and Norway were included. We did quality assessment of the guidelines according to the AGREEMENT tool. We performed a meta-analysis assessing the effects of IA with a Doppler device vs. Pinard device using methods described in TheCochrane Handbook, and we performed an overall assessment of the summary of evidence using the GRADE approach. Results The searches generated 6408 hits of which 26 studies and 11 guidelines were included in the review. The studies described slightly different techniques for performing IA, and some did not provide detailed descriptions. Few of the studies provided details of normal and abnormal IA findings. All 11 guidelines recommended IA for low risk women, although they had slightly different recommendations on the frequency, timing, and duration for IA, and the FHR characteristics that should be observed. Four of the included studies, comprising 8436 women and their babies, were randomised controlled trials that evaluated the effect of IA with a Doppler device vs. a Pinard device. Abnormal FHRs were detected more often using the Doppler device than in those using the Pinard device (risk ratio 1.77; 95% confidence interval 1.29–2.43). There were no significant differences in any of the other maternal or neonatal outcomes. Four studies assessed the accuracy of IA findings. Normal FHR was easiest to identify correctly, whereas identifying periodic FHR patterns such as decelerations and saltatory patterns were more difficult. Conclusion Although IA is the recommended method, no trials have been published that evaluate protocols on how to perform it. Nor has any study assessed interrater agreements regarding interpretations of IA findings, and few have assessed to what degree clinicians can describe FHR patterns detected by IA. We found no evidence to recommend Doppler device instead of the Pinard for IA, or vice versa. Intermittent auscultation fetal monitoring during labour: A systematic scoping review to identify methods, effects, and accuracy

ObjectivesFetal alcohol spectrum disorders (FASD) is a worldwide problem. Maternal alcohol consumption is an important risk factor for FASD. It remains unknown which alcohol consumption patterns most strongly predict FASD. The objective of this study was to identify these.DesignSystematic literature review.MethodsWe searched in PubMed, PsychINFO, PsycARTICLES, ERIC, CINAHL, Embase and MEDLINE up to August 2018. The query consisted of keywords and their synonyms related to FASD, pregnancy and behaviour. Studies were excluded when not published in English, were reviews or involved non-human subjects. Substantial heterogeneity precluded aggregation or meta-analysis of the data. Instead, data were qualitatively inspected.ResultsIn total, 21 studies were eligible for further data analysis. All studies that measured both maternal alcohol drinking behaviours and FASD reported retrospective data on maternal drinking patterns, employing both continuous and categorical measures and exhibiting substantial heterogeneity in measures of alcohol consumption (eg, timing of exposure, quantification of alcohol measure and definition of a standard drink). Study quality improved over time and appeared higher for studies based on active case ascertainment, especially when conducted in schools and when behaviour was assessed through interviews.ConclusionsWe aimed to identify specific maternal drinking behaviour(s) related to FASD. The state of the literature precludes such conclusions. Evidence-based preventive measures necessitate identifying which prenatal alcohol drinking behaviour(s) are most in need of intervention. Therefore, we formulate three recommendations for future research. First, future studies can optimise the value of the collected dataset through specifying measurements and reporting of maternal drinking behaviours and avoiding categorised measures (nominal or ordinal) whenever possible. Second, samples should not be selected based on FASD status, but instead, FASD status as well as maternal alcohol consumption should both be measured in a general population sample. Finally, we provide 10 reporting guidelines for FASD research.

Simple SummaryHealth behaviors affect health status in cancer survivors. We aimed to identify such key health behaviors using nonlinear algorithms and compare their classification performance with logistic regression, for distinguishing cancer survivors from those cancer-free in a population-based cohort. We used health behaviors and socioeconomic factors for analysis. Participants from the Lifelines population-based cohort were binary classified as cancer survivors or cancer-free using nonlinear algorithms or logistic regression. Data were collected for 107,624 cancer-free participants and 2760 cancer survivors. Using all variables, algorithms obtained an area under the receiver operator curve (AUC) of 0.75 +/- 0.01. Using only health behaviors, the algorithms differentiated cancer survivors from cancer-free participants with AUCs of 0.62 +/- 0.01 and 0.60 +/- 0.01, respectively. In the case-control analyses, both algorithms produced AUCs of 0.52 +/- 0.01. The main distinctive classifier was age. No key health behaviors were identified by linear and nonlinear algorithms to differentiate cancer survivors from cancer-free participants.Health behaviors affect health status in cancer survivors. We hypothesized that nonlinear algorithms would identify distinct key health behaviors compared to a linear algorithm and better classify cancer survivors. We aimed to use three nonlinear algorithms to identify such key health behaviors and compare their performances with that of a logistic regression for distinguishing cancer survivors from those without cancer in a population-based cohort study. We used six health behaviors and three socioeconomic factors for analysis. Participants from the Lifelines population-based cohort were binary classified into a cancer-survivors group and a cancer-free group using either nonlinear algorithms or logistic regression, and their performances were compared by the area under the curve (AUC). In addition, we performed case-control analyses (matched by age, sex, and education level) to evaluate classification performance only by health behaviors. Data were collected for 107,624 cancer free participants and 2760 cancer survivors. Using all variables resulted an AUC of 0.75 +/- 0.01, using only six health behaviors, the logistic regression and nonlinear algorithms differentiated cancer survivors from cancer-free participants with AUCs of 0.62 +/- 0.01 and 0.60 +/- 0.01, respectively. The main distinctive classifier was age. Though not relevant to classification, the main distinctive health behaviors were body mass index and alcohol consumption. In the case-control analyses, algorithms produced AUCs of 0.52 +/- 0.01. No key health behaviors were identified by linear and nonlinear algorithms to differentiate cancer survivors from cancer-free participants in this population-based cohort.

Individuals with attention deficit/hyperactivity disorder (ADHD) are at increased risk of developing substance use disorders (SUDs) and nicotine dependence. The co-occurrence of ADHD and SUDs/nicotine dependence may in part be mediated by shared genetic liability. Several neurobiological pathways have been implicated in both ADHD and SUDs, including dopamine and serotonin pathways. We hypothesized that variations in dopamine and serotonin neurotransmission genes were involved in the genetic liability to develop SUDs/nicotine dependence in ADHD. The current study included participants with ADHD (n=280) who were originally part of the Dutch International Multicenter ADHD Genetics study. Participants were aged 5-15 years and attending outpatient clinics at enrollment in the study. Diagnoses of ADHD, SUDs, nicotine dependence, age of first nicotine and substance use, and alcohol use severity were based on semi-structured interviews and questionnaires. Genetic risk scores were created for both serotonergic and dopaminergic risk genes previously shown to be associated with ADHD and SUDs and/or nicotine dependence. The serotonin genetic risk score significantly predicted alcohol use severity. No significant serotoninxdopamine risk score or effect of stimulant medication was found. The current study adds to the literature by providing insight into genetic underpinnings of the co-morbidity of ADHD and SUDs. While the focus of the literature so far has been mostly on dopamine, our study suggests that serotonin may also play a role in the relationship between these disorders.

Purpose Optimizing a therapeutic product's benefit-risk profile is an on-going process throughout the product's life cycle. Different, yet related, benefit-risk assessment strategies and frameworks are being developed by various regulatory agencies, industry groups, and stakeholders. This paper summarizes current best practices and discusses the role of the pharmacoepidemiologist in these activities, taking a life-cycle approach to integrated Benefit-Risk Assessment, Communication, and Evaluation (BRACE). Methods A review of the medical and regulatory literature was performed for the following steps involved in therapeutic benefit-risk optimization: benefit-risk evidence generation; data integration and analysis; decision making; regulatory and policy decision making; benefit-risk communication and risk minimization; and evaluation. Feedback from International Society for Pharmacoepidemiology members was solicited on the role of the pharmacoepidemiologist. The case example of natalizumab is provided to illustrate the cyclic nature of the benefit-risk optimization process. Results No single, globally adopted benefit-risk assessment process exists. The BRACE heuristic offers a way to clarify research needs and to promote best practices in a cyclic and integrated manner and highlight the critical importance of cross-disciplinary input. Its approach focuses on the integration of BRACE activities for risk minimization and optimization of the benefit-risk profile. Conclusion The activities defined in the BRACE heuristic contribute to the optimization of the benefit-risk profile of therapeutic products in the clinical world at both the patient and population health level. With interdisciplinary collaboration, pharmacoepidemiologists are well suited for bringing in methodology expertise, relevant research, and public health perspectives into the BRACE process. Copyright (C) 2015 John Wiley & Sons, Ltd.

Much of the published medical research is apparently flawed, cannot be replicated and/or has limited or no utility. This article presents an overview of the current landscape of biomedical research, identifies problems associated with common study designs and considers potential solutions. Randomized clinical trials, observational studies, systematic reviews and meta-analyses are discussed in terms of their inherent limitations and potential ways of improving their conduct, analysis and reporting. The current emphasis on statistical significance needs to be replaced by sound design, transparency and willingness to share data with a clear commitment towards improving the quality and utility of clinical research.

BACKGROUND: Storage time of platelet (PLT) concentrates has been negatively associated with clinical efficacy outcomes. The aim of this study was to quantify the association between storage time of PLT concentrates and interval to the next PLT transfusion for different types of PLT components, stored for up to 7 days and transfused to transfusion-dependent hematooncology patients with thrombocytopenia. STUDY DESIGN AND METHODS: From a cohort of patients from 10 major Dutch hospitals, patients were selected whose transfusion patterns were compatible with PLT transfusion dependency due to hematooncologic disease. Mean time to the next transfusion and mean differences in time to the next transfusion for different storage time categories (i.e., fresh, 5 days) were estimated, per component type, using multilevel mixed-effects linear models. RESULTS: Among a cohort of 29,761 patients who received 140,896 PLT transfusions we selected 4441 hematooncology patients who had received 12,724 PLT transfusions during periods of PLT transfusion dependency. Transfusion of fresh, compared to old, buffy coat–derived PLTs in plasma was associated with a delay to the next transfusion of 6.2 hours (95% confidence interval [CI], 4.5-8.0 hr). For buffy coat–derived PLTs in PAS-B and -C this difference was 7.7 hours (95% CI, 2.2-13.3 hr) and 3.9 hours (95% CI, –2.1 to 9.9 hr) while for apheresis PLTs in plasma it was only 1.8 hours (95% CI, –3.5 to 7.1 hr). CONCLUSION: Our results indicate that the time to the next transfusion shortens with increasing age of transfused buffy coat–derived PLT concentrates. This association was not observed for apheresis PLTs.