House dust mite allergen avoidance strategies for the treatment of allergic asthma:A hypothesis-generating meta-analysis

Background: This study continues the review by Gøtzsche and Johansen (Cochrane Database of Systematic Reviews, 2008, Art. No: CD001187), aiming to systematically generate hypotheses on the effectiveness of (sub)strategies for house dust mite allergen avoidance in the treatment of allergic asthma. Methods: We used the trials previously analysed by Gøtzsche and Johansen and searched recently published studies. Data on asthma symptom scores (ASS), ACQ, number of improved patients, AQLQ-scores, medication use, FEV1%, PC20, and FeNO levels were analysed. The effectiveness of strategies was assessed using Metafor in R. Results: Thirty-five trials involving 2419 patients were included in the final study. The patient-reported outcome number of patients with improved condition following total bedroom control was RR = 3.39 (95% confidence interval: 1.04 to 11.04, P = 0.04). The mean differences in the ASS by nocturnal air purification was −0.7 (95% confidence interval: −1.08 to −0.32, P &lt; 0.001). Other outcomes including partial bedroom control were non-significant or clinically not of importance. Conclusions: Total bedroom control and nocturnal air purification of the breathing zone hypothetically provides clinical benefits in patients with house dust mite-induced allergic asthma. The number of patients with improvements in their condition respectively the asthma symptom score differences showed potential in small subgroups, consisting of single studies. Partial bedroom control is not recommended. Systematic Review Registration: Prospero CRD42022323660.</p

Male Sexual Health and Reproduction in Cutaneous Immune-Mediated Diseases: A Systematic Review

Introduction: Information about the possible effects of cutaneous immune-mediated diseases (cIMDs) on male sexual function and reproduction is scarce. Factors known to impair sexual health and reproduction, such as inflammation, medication use, and hypogonadism, can be present in a significant proportion of male patients with cIMD. Objectives: To systematically review the literature for the influence of paternal cIMD on many aspects of male sexual and reproductive health, such as sexual function, reproductive hormones, fertility, and pregnancy and offspring outcomes. Methods: A systematic literature search was performed. The searches combined keywords regarding male sexual function and fertility, pregnancy outcomes, and offspring's health with a list of cIMDs. Results: The majority of the identified studies included patients with psoriasis (22 of 27), and sexual function was the most common outcome of interest (20 of 27). For patients diagnosed with psoriasis, the prevalence of male sexual dysfunction reported in these studies ranged from 34 to 81%. Hypogonadism in patients with psoriasis was reported in 2 of 3 studies. Sperm analysis abnormalities in patients with psoriasis were reported in 3 of 4 studies. No information about the effect of paternal disease on pregnancy and offspring outcomes was identified. Conclusions: Disease activity in psoriasis might play an important role in the development of sexua

The effect of paternal exposure to immunosuppressive drugs on sexual function, reproductive hormones, fertility, pregnancy and offspring outcomes: A systematic review

BACKGROUND: Information regarding the possible influence of immunosuppressive drugs on male sexual function and reproductive outcomes is scarce. Men diagnosed with immune-mediated diseases and a wish to become a father represent an important neglected population since they lack vital information to make balanced decisions about their treatment. OBJECTIVE AND RATIONALE: The aim of this research was to systematically review the literature for the influence of paternal immunosuppressive drug use on many aspects of male sexual health, such as sexual function, fertility, pregnancy outcomes and offspring health outcomes. SEARCH METHODS: A systematic literature search was performed in the bibliographic databases: Embase (via Elsevier embase.com), MEDLINE ALL via Ovid, Cochrane Central Register of Trials (via Wiley) and Web of Science Core Collection. Additionally, Google Scholar and the Clinical trial registries of Europe and the USA were searched. The databases were searched from inception until 31 August 2019. The searches combined keywords regarding male sexual function and fertility, pregnancy outcomes and offspring health with a list of immunosuppressive drugs. Studies were included if they were published in English and if they included original data on male human exposure to immunosuppressive drugs. A meta-analysis was not possible to perform due to the heterogeneity of the data. OUTCOMES: A total of 5867 references were identified, amongst which we identified 161 articles fulfilling the eligibility criteria. Amongst these articles, 50 included pregnancy and offspring outcomes and 130 included sexual health outcomes. Except for large Scandinavian cohorts, most of the identified articles included a small number of participants. While a clear negative effect on sperm quality was evident for sulfasalazine and cyclophosphamide, a dubious effect was identified for colchicine, methotrexate and sirolimus. In three articles, exposure to tumour necrosis factor-a inhibitors in patients diagnosed with ankylosing spondylitis resulted in improved sperm quality. The information regarding pregnancy and offspring outcomes was scant but no large negative effect associated with paternal immunosuppressiv

Preoperative anaemia and outcome after elective cardiac surgery:a Dutch national registry analysis

Background: Previous studies have shown that preoperative anaemia in patients undergoing cardiac surgery is associated with adverse outcomes. However, most of these studies were retrospective, had a relatively small sample size, and were from a single centre. The aim of this study was to analyse the relationship between the severity of preoperative anaemia and short- and long-term mortality and morbidity in a large multicentre national cohort of patients undergoing cardiac surgery. Methods: A nationwide, prospective, multicentre registry (Netherlands Heart Registration) of patients undergoing elective cardiac surgery between January 2013 and January 2019 was used for this observational study. Anaemia was defined according to the WHO criteria, and the main study endpoint was 120-day mortality. The association was investigated using multivariable logistic regression analysis. Results: In total, 35 484 patients were studied, of whom 6802 (19.2%) were anaemic. Preoperative anaemia was associated with an increased risk of 120-day mortality (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI]: 1.4–1.9; P<0.001). The risk of 120-day mortality increased with anaemia severity (mild anaemia aOR 1.6; 95% CI: 1.3–1.9; P<0.001; and moderate-to-severe anaemia aOR 1.8; 95% CI: 1.4–2.4; P<0.001). Preoperative anaemia was associated with red blood cell transfusion and postoperative morbidity, the causes of which included renal failure, pneumonia, and myocardial infarction. Conclusions: Preoperative anaemia was associated with mortality and morbidity after cardiac surgery. The risk of adverse outcomes increased with anaemia severity. Preoperative anaemia is a potential target for treatment to improve postoperative outcomes

Evaluating deterministic motif significance measures in protein databases

<p>Abstract</p> <p>Background</p> <p>Assessing the outcome of motif mining algorithms is an essential task, as the number of reported motifs can be very large. Significance measures play a central role in automatically ranking those motifs, and therefore alleviating the analysis work. Spotting the most interesting and relevant motifs is then dependent on the choice of the right measures. The combined use of several measures may provide more robust results. However caution has to be taken in order to avoid spurious evaluations.</p> <p>Results</p> <p>From the set of conducted experiments, it was verified that several of the selected significance measures show a very similar behavior in a wide range of situations therefore providing redundant information. Some measures have proved to be more appropriate to rank highly conserved motifs, while others are more appropriate for weakly conserved ones. Support appears as a very important feature to be considered for correct motif ranking. We observed that not all the measures are suitable for situations with poorly balanced class information, like for instance, when positive data is significantly less than negative data. Finally, a visualization scheme was proposed that, when several measures are applied, enables an easy identification of high scoring motifs.</p> <p>Conclusion</p> <p>In this work we have surveyed and categorized 14 significance measures for pattern evaluation. Their ability to rank three types of deterministic motifs was evaluated. Measures were applied in different testing conditions, where relations were identified. This study provides some pertinent insights on the choice of the right set of significance measures for the evaluation of deterministic motifs extracted from protein databases.</p

The survival disparity between children and adolescents and young adults (AYAs) with Ewing sarcoma in the Netherlands did not change since the 1990s despite improved survival: A population-based study

Background: Adolescents and young adults (AYAs) with Ewing sarcoma have a worse prognosis than children. Population-based survival evaluations stratifying findings by important clinical factors are, however, limited. This Dutch population study comprehensively compared survival of children and AYAs with Ewing sarcoma over three decades considering diagnostic period, tissue of origin, tumor site, and disease stage. Methods: Data on all children (0–17 years, N = 463) and AYAs (18–39 years, N = 379) diagnosed with Ewing sarcoma in the Netherlands between 1990–2018 were collected from the Netherlands Cancer Registry with follow-up until February 2023. Five-year relative survival was calculated using the cohort method. Multivariable analyses were conducted through Poisson regression. Results: Children with Ewing sarcoma had a significantly higher 5-year relative survival than AYAs (65 % vs. 44 %). An increasing trend in survival was noted reaching 70 % in children and 53 % in AYAs in 2010–2018. Results were similar for Ewing bone sarcoma and extraosseous Ewing sarcoma. AYAs had a poorer prognosis than children for most tumor sites and regardless of disease stage. Survival probabilities were 60 % vs. 78 % for localized disease and 20 % vs. 33 % for metastatic disease. Multivariable-regression analysis, adjusted for follow-up time, diagnostic period, sex, disease stage, and tumor site, confirmed increased excess mortality among AYAs compared with children (excess HR: 1.7, 95 % CI: 1.3–2.1). Conclusions: Despite survival improvements since the 1990s, AYAs with Ewing sarcoma in the Netherlands continue to fare considerably worse than children

Tobacco use induces anti-apoptotic, proliferative patterns of gene expression in circulating leukocytes of Caucasian males

Abstract Background Strong epidemiologic evidence correlates tobacco use with a variety of serious adverse health effects, but the biological mechanisms that produce these effects remain elusive. Results We analyzed gene transcription data to identify expression spectra related to tobacco use in circulating leukocytes of 67 Caucasian male subjects. Levels of cotinine, a nicotine metabolite, were used as a surrogate marker for tobacco exposure. Significance Analysis of Microarray and Gene Set Analysis identified 109 genes in 16 gene sets whose transcription levels were differentially regulated by nicotine exposure. We subsequently analyzed this gene set by hyperclustering, a technique that allows the data to be clustered by both expression ratio and gene annotation (e.g. Gene Ontologies). Conclusion Our results demonstrate that tobacco use affects transcription of groups of genes that are involved in proliferation and apoptosis in circulating leukocytes. These transcriptional effects include a repertoire of transcriptional changes likely to increase the incidence of neoplasia through an altered expression of genes associated with transcription and signaling, interferon responses and repression of apoptotic pathways

Overview of data-synthesis in systematic reviews of studies on outcome prediction models

Background: Many prognostic models have been developed. Different types of models, i.e. prognostic factor and outcome prediction studies, serve different purposes, which should be reflected in how the results are summarized in reviews. Therefore we set out to investigate how authors of reviews synthesize and report the results of primary outcome prediction studies. Methods: Outcome prediction reviews published in MEDLINE between October 2005 and March 2011 were eligible and 127 Systematic reviews with the aim to summarize outcome prediction studies written in English were identified for inclusion. Characteristics of the reviews and the primary studies that were included were independently assessed by 2 review authors, using standardized forms. Results: After consensus meetings a total of 50 systematic reviews that met the inclusion criteria were included. The type of primary studies included (prognostic factor or outcome prediction) was unclear in two-thirds of the reviews. A minority of the reviews reported univariable or multivariable point estimates and measures of dispersion from the primary studies. Moreover, the variables considered for outcome prediction model development were often not reported, or were unclear. In most reviews there was no information about model performance. Quantitative analysis was performed in 10 reviews, and 49 reviews assessed the primary studies qualitatively. In both analyses types a range of different methods was used to present the results of the outcome prediction studies. Conclusions: Different methods are applied to synthesize primary study results but quantitative analysis is rarely performed. The description of its objectives and of the primary studies is suboptimal and performance parameters of the outcome prediction models are rarely mentioned. The poor reporting and the wide variety of data synthesis strategies are prone to influence the conclusions of outcome prediction reviews. Therefore, there is much room for improvement in reviews of outcome prediction studies. (aut.ref.

Climatic predictors of species distributions neglect biophysiologically meaningful variables

This is the final version. Available on open access from Wiley via the DOI in this record.Aim: Species distribution models (SDMs) have played a pivotal role in predicting how species might respond to climate change. To generate reliable and realistic predictions from these models requires the use of climate variables that adequately capture physiological responses of species to climate and therefore provide a proximal link between climate and their distributions. Here, we examine whether the climate variables used in plant SDMs are different from those known to influence directly plant physiology. Location: Global. Methods: We carry out an extensive, systematic review of the climate variables used to model the distributions of plant species and provide comparison to the climate variables identified as important in the plant physiology literature. We calculate the top ten SDM and physiology variables at 2.5 degree spatial resolution for the globe and use principal component analyses and multiple regression to assess similarity between the climatic variation described by both variable sets. Results: We find that the most commonly used SDM variables do not reflect the most important physiological variables and differ in two main ways: (i) SDM variables rely on seasonal or annual rainfall as simple proxies of water available to plants and neglect more direct measures such as soil water content; and (ii) SDM variables are typically averaged across seasons or years and overlook the importance of climatic events within the critical growth period of plants. We identify notable differences in their spatial gradients globally and show where distal variables may be less reliable proxies for the variables to which species are known to respond. Main conclusions: There is a growing need for the development of accessible, fine-resolution global climate surfaces of physiological variables. This would provide a means to improve the reliability of future range predictions from SDMs and support efforts to conserve biodiversity in a changing climate

Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study

Background: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors – healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. Results: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. Conclusions: Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention. Electronic supplementary material The online version of this article (doi:10.1186/s12916-014-0168-4) contains supplementary material, which is available to authorized users