Identification of Retracted Publications and Completeness of Retraction Notices in Public Health.

OBJECTIVES: Retraction is intended to be a mechanism to correct the published body of knowledge when necessary due to fraudulent, fatally flawed or ethically unacceptable publications. However, the success of this mechanism requires that retracted publications be consistently identified as such and that retraction notices contain sufficient information to understand what is being retracted and why. Our study investigated how clearly and consistently retracted publications in public health are being presented to researchers. STUDY DESIGN AND SETTING: This is a cross-sectional study, using 441 retracted research publications in the field of public health. Records were retrieved for each of these publications from 11 resources, while retraction notices were retrieved from publisher websites and full-text aggregators. The identification of the retracted status of the publication was assessed using criteria from the Council on Publication Ethics (COPE) and the National Library of Medicine (NLM). The completeness of the associated retraction notices was assessed using criteria from COPE and Retraction Watch. RESULTS: 2841 records for retracted publications were retrieved, of which less than half indicated that the article had been retracted. Less than 5% of publications were identified as retracted through all resources through which they were available. Within single resources, if and how retracted publications were identified varied. Retraction notices were frequently incomplete, with no notices meeting all criteria. CONCLUSIONS: The observed inconsistencies and incomplete notices pose a threat to the integrity of scientific publishing and highlight the need to better align with existing best practices to ensure more effective and transparent dissemination of information on retractions.

High vaccine effectiveness against severe COVID-19 outcomes and population preventable fraction during the Omicron era in Luxembourg: A nationwide retrospective risk factor analysis.

BACKGROUND: Luxembourg experienced major consecutive SARS-CoV-2 infection waves due to Omicron variants during 2022 while having achieved a high vaccination coverage in 2021. We investigated the risk factors associated to severe outcomes (i.e., hospitalisation, deaths) and estimated vaccine effectiveness (VE) as well as the role of immunity conferred by prior infections against severe outcomes in adults. METHODS: We linked reported SARS-CoV-2 cases among residents aged ≥ 20 years with vaccination data and SARS-CoV-2 related hospitalisations and deaths. Cases were followed-up until day 14 for COVID-19 related hospital admission and up to day 28 for mortality after a positive test. We analysed the association between the vaccination status and severe forms using proportional Cox regression, adjusting for previous infection, age, sex and nursing homes residency. VE was measured as 1-adjusted hazard ratio of vaccinated vs unvaccinated individuals. The population preventable fraction was computed using the adjusted hazard ratio and the proportion of cases within the vaccination category. RESULTS: Between December 2021, and March 2023, we recorded 187143 SARS-CoV-2 cases, 1728 (0.93%) hospitalizations and 611 (0.33%) deaths. The risk of severe outcomes increased with age, was higher among men and nursing home residents. Compared to unvaccinated adults, VE against hospitalization was 38.8% (95%CI: 28.1%-47.8%) for a complete primary cycle of vaccination, 62.1% (95%CI: 57.0%-66.7%) for one booster, and 71.6% (95%CI: 66.7%-76.2%) for two booster doses. VE against death was respectively 49.5% (95%CI: 30.8%-63.3%), 69.0% (95%CI: 61.2%-75.3%) and 76.2% (95%CI: 68.4%-82.2%). Previous infection was not associated with lower risk of hospitalisation or mortality. The vaccination lowered mortality by 55.8 % (95%CI: 46.3%-62.8%) and reduced hospital admissions by 49.1% (95%CI: 43.4%-54.4%). CONCLUSIONS: Complete vaccination and booster but not previous infection were protective against hospitalization and death. The vaccination program in Luxembourg led to substantial reductions in SARS-CoV-2-related mortality and hospitalizations at the population level.

Changes in acceptability, consideration, intention, and uptake of direct-to-consumer genetic tests in the Netherlands from 2017 to 2022.

Although the popularity of direct-to-consumer genetic tests (DTC-GT) for disease-related purposes increased, concerns persist whether consumers make well-informed decisions about their purchase. To better target pre- and post-test information materials, this study aims to determine the characteristics of people interested in undergoing DTC-GT. In addition, it aims to determine changes in acceptability, consideration, intention, and uptake of DTC-GT since 2017. An online cross-sectional survey was conducted in April 2022 with a representative sample of the Dutch adult population. Ordinal regression models and chi-squared tests were used to determine factors associated with DTC-GT acceptability, consideration and intention, and changes in outcomes since 2017, respectively. Of the 907 included respondents, 19.3% found DTC-GT acceptable, 29.4% considered taking a DTC-GT in the future, 6.2% intended to take a test within the coming year, and 0.9% had already tested. High education was associated with lower acceptability, consideration, intention, and higher awareness. Respondents with a chronic disease were less likely to find DTC-GT acceptable. Higher consideration was associated with having a partner, adopted/stepchildren, and lower age. Compared to 2017, in 2022 more respondents found DTC-GT totally unacceptable, while more considered testing, and fewer ruled out taking a test both in the next year and the future. Education status may play an important role in people's acceptability, consideration, intention, and awareness of disease-related DTC-GT in the Netherlands. Easy-to-understand public information materials should be promoted and guidance is needed to help with decision-making and result interpretation. Future research should focus on the best way to provide responsible guidance.

Fruits and vegetables intake and bladder cancer risk: a pooled analysis from 11 case-control studies in the BLadder cancer Epidemiology and Nutritional Determinants (BLEND) consortium.

PURPOSE: High consumption of fruits and vegetables decrease the risk of bladder cancer (BC). The evidence of specific fruits and vegetables and the BC risk is still limited. METHODS: Fruit and vegetable consumptions in relation to BC risk was examined by pooling individual participant data from case-control studies. Unconditional logistic regression was used to estimate study-specific odds ratio's (ORs) with 95% confidence intervals (CIs) and combined using a random-effects model for intakes of total fruits, total vegetables, and subgroups of fruits and vegetables. RESULTS: A total of 11 case-control studies were included, comprising 5637 BC cases and 10,504 controls. Overall, participants with the highest intakes versus the lowest intakes of fruits in total (OR 0.79; 95% CI 0.68-0.91), citrus fruits (OR 0.81; 95% CI 0.65-0.98), pome fruits (OR 0.76; 95% CI 0.65-0.87), and tropical fruits (OR 0.84; 95% CI 0.73-0.94) reduced the BC risk. Greater consumption of vegetables in total, and specifically shoot vegetables, was associated with decreased BC risk (OR 0.82; 95% CI 0.68-0.96 and OR 0.87; 95% CI 0.78-0.96, respectively). Substantial heterogeneity was observed for the associations between citrus fruits and total vegetables and BC risk. CONCLUSION: This comprehensive study provides compelling evidence that the consumption of fruits overall, citrus fruits, pome fruits and tropical fruits reduce the BC risk. Besides, evidence was found for an inverse association between total vegetables and shoot vegetables intake.

[Opioid use and misuse among patients at the emergency department]. / Opioïdgebruik en -misbruik onder patiënten op de SEH.

OBJECTIVE: To determine the prevalence of use and misuse of prescription opioids among patients at Dutch emergency departments (EDs). DESIGN: Cross-sectional multicenter study. METHOD: This study was performed at three EDs in the Nijmegen-Arnhem region. ED-patients of 18 years and older were screened for current opioid use. The Current Opioid Misuse Measure (COMM) questionnaire was used to assess opioid misuse. The presence of opioid use disorder was determined using DSM-5 based interviews. RESULTS: A total of 997 patients was screened for opioid use. The prevalence of opioid use was 15.0% (95%CI 12.9 -17.4). 22.6% (95%CI 14.6-32.4) scored positive for opioid misuse, 9.8% (95%CI 4.5-17.8) fulfilled DSM-5 criteria for opioid use disorder. CONCLUSION: Opioid use and misuse are relatively common among patients in Dutch EDs.

Poly(methylmethacrylate-co-dimethyl acrylamide)-silver nanocomposite prevents biofilm formation in medical devices.

Aim: To investigate whether medical devices coated with a synthesized nanocomposite of poly(methylmethacrylate-co-dimethyl acrylamide) (PMMDMA) and silver nanoparticles (AgNPs) could improve their antibiofilm and antimicrobial activities. We also investigated the nanocomposite's safety. Materials & methods: The nanocomposite was synthesized and characterized using analytical techniques. Medical devices coated with the nanocomposite were evaluated for bacterial adhesion and hemolytic activity in vitro. Results: The nanocomposite formation was demonstrated with the incorporation of AgNPs into the polymer matrix. The nanocomposite proved to be nonhemolytic and significantly inhibited bacterial biofilm formation. Conclusion: The PMMDMA-AgNPs nanocomposite was more effective in preventing biofilm formation than PMMDMA alone and is a promising strategy for coating medical devices and reducing mortality due to hospital-acquired infections.

External Quality Assessment on Molecular Tumor Profiling with Circulating Tumor DNA-Based Methodologies Routinely Used in Clinical Pathology within the COIN Consortium.

BACKGROUND: Identification of tumor-derived variants in circulating tumor DNA (ctDNA) has potential as a sensitive and reliable surrogate for tumor tissue-based routine diagnostic testing. However, variations in pre(analytical) procedures affect the efficiency of ctDNA recovery. Here, an external quality assessment (EQA) was performed to determine the performance of ctDNA mutation detection work flows that are used in current diagnostic settings across laboratories within the Dutch COIN consortium (ctDNA on the road to implementation in The Netherlands). METHODS: Aliquots of 3 high-volume diagnostic leukapheresis (DLA) plasma samples and 3 artificial reference plasma samples with predetermined mutations were distributed among 16 Dutch laboratories. Participating laboratories were requested to perform ctDNA analysis for BRAF exon 15, EGFR exon 18-21, and KRAS exon 2-3 using their regular circulating cell-free DNA (ccfDNA) analysis work flow. Laboratories were assessed based on adherence to the study protocol, overall detection rate, and overall genotyping performance. RESULTS: A broad range of preanalytical conditions (e.g., plasma volume, elution volume, and extraction methods) and analytical methodologies (e.g., droplet digital PCR [ddPCR], small-panel PCR assays, and next-generation sequencing [NGS]) were used. Six laboratories (38%) had a performance score of >0.90; all other laboratories scored between 0.26 and 0.80. Although 13 laboratories (81%) reached a 100% overall detection rate, the therapeutically relevant EGFR p.(S752_I759del) (69%), EGFR p.(N771_H773dup) (50%), and KRAS p.(G12C) (48%) mutations were frequently not genotyped accurately. CONCLUSIONS: Divergent (pre)analytical protocols could lead to discrepant clinical outcomes when using the same plasma samples. Standardization of (pre)analytical work flows can facilitate the implementation of reproducible liquid biopsy testing in the clinical routine.

An Atlas of Dietary Intakes and Medication Uses on Risk of Bladder Cancer: A Wide-Angle Mendelian Randomization Analysis.

BACKGROUND: Observational studies suggests that diets and medications affect bladder cancer (BC) development, which are subject to confounding and difficult to make causal inference. Here we aimed to investigate whether those observational associations are causal and determining the potential directions and pathways. METHODS: We used 2-sample Mendelian randomization (MR) analysis to assess associations of dietary intakes, medication uses and molecules with BC risk. Genetic summary data were derived from participants of predominantly European ancestry with rigorous instruments selection, where univariable MR, mediation MR and multivariable MR were performed. RESULTS: The results of univariable MR showed 4 dietary intakes and 4 medication uses having a protective effect on BC, while 4 circulating metabolites, 440 circulating proteins and 2 gut microbes were observed to be causally associated with BC risk. Through mediation MR, we found 572 analytes showing consistent mediating effects between dietary intakes or medication uses and BC risk. Furthermore, 9 out of 16 diet-medication pairs showed significant interactions and alterations on BC when consumed jointly. CONCLUSION: In summary, the findings obtained from the current study have important implications for informing prevention strategies that point to potential lifestyle interventions or medication prescriptions to reduce the risk of developing BC.HighlightsThe current study extends observational literature in showing the importance of diets and medications on bladder cancer prevention.The associations of diets and medications on bladder cancer prevention might be through circulating metabolites, circulating proteins and gut microbiotaOur results provide a new understanding of interactions in certain diet-medication pairs which should be taken into account by both physicians and patients during the development of a treatment strategy.

Tropomyosin1 isoforms underlie epithelial to mesenchymal plasticity, metastatic dissemination, and resistance to chemotherapy in high-grade serous ovarian cancer.

Phenotypic plasticity, defined as the ability of individual cells with stable genotypes to exert different phenotypes upon exposure to specific environmental cues, represent the quintessential hallmark of the cancer cell en route from the primary lesion to distant organ sites where metastatic colonization will occur. Phenotypic plasticity is driven by a broad spectrum of epigenetic mechanisms that allow for the reversibility of epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions (EMT/MET). By taking advantage of the co-existence of epithelial and quasi-mesenchymal cells within immortalized cancer cell lines, we have analyzed the role of EMT-related gene isoforms in the regulation of epithelial mesenchymal plasticity (EMP) in high grade serous ovarian cancer. When compared with colon cancer, a distinct spectrum of downstream targets characterizes quasi-mesenchymal ovarian cancer cells, likely to reflect the different modalities of metastasis formation between these two types of malignancy, i.e. hematogenous in colon and transcoelomic in ovarian cancer. Moreover, upstream RNA-binding proteins differentially expressed between epithelial and quasi-mesenchymal subpopulations of ovarian cancer cells were identified that underlie differential regulation of EMT-related isoforms. In particular, the up- and down-regulation of RBM24 and ESRP1, respectively, represent a main regulator of EMT in ovarian cancer cells. To validate the functional and clinical relevance of our approach, we selected and functionally analyzed the Tropomyosin 1 gene (TPM1), encoding for a protein that specifies the functional characteristics of individual actin filaments in contractile cells, among the ovarian-specific downstream AS targets. The low-molecular weight Tpm1.8/9 isoforms are specifically expressed in patient-derived ascites and promote invasion through activation of EMT and Wnt signaling, together with a broad spectrum of inflammation-related pathways. Moreover, Tpm1.8/9 expression confers resistance to taxane- and platinum-based chemotherapy. Small molecule inhibitors that target the Tpm1 isoforms support targeting Tpm1.8/9 as therapeutic targets for the development of future tailor-made clinical interventions.

The prevalence of prescription opioid use and misuse among emergency department patients in The Netherlands.

RATIONALE: Prescription opioid use and misuse have increased rapidly in many Western countries in the past decade. Patients (mis)using opioids are at risk of presenting to the emergency department (ED) with opioid-related problems. European data concerning prescription opioid (mis)use among the ED population is lacking. AIMS AND OBJECTIVES: This study aims to determine prevalence of prescription opioid use, misuse, and opioid use disorder (OUD) among Dutch ED patients. Secondary objectives were to explore factors associated with prescription opioid misuse and the number of patients discharged with a new opioid prescription. METHODS: In a cross-sectional multicenter study at three hospitals in the Netherlands, adult ED patients were screened for current prescription opioid use. Opioid users filled out questionnaires regarding opioid (mis)use, and underwent a structured interview to assess OUD criteria. The primary outcomes were prevalence rates of (1) current prescription opioid use, (2) prescription opioid misuse (based on a Current Opioid Misuse Measure [COMM] score > 8), (3) OUD, based on DSM-5 criteria. Independent T-tests, Pearson χ2 and Fisher's Exact tests were used to analyse differences in characteristics between groups. RESULTS: A total of 997 patients were screened, of which 15% (n = 150) used prescription opioids. Out of 93 patients assessed, 22.6% (n = 21) showed signs of prescription opioid misuse, and 9.8% (n = 9, 95% CI: 4.5-17.8) fulfilled criteria for OUD. A medical history of psychiatric disorder was significantly more common in patients with prescription opioid misuse and OUD. CONCLUSION: This study shows that prescription opioid use is relatively common in ED patients in the Netherlands, compared to the overall population. Over one fifth of these patients shows signs of opioid misuse or OUD. Awareness among ED personnel about the high prevalence of prescription opioid (mis)use in their population is critical for signalling opioid-related problems.

Systematic review search strategies are poorly reported and not reproducible: a cross-sectional metaresearch study.

OBJECTIVES: To determine the reproducibility of biomedical systematic review search strategies. STUDY DESIGN AND SETTING: A cross-sectional reproducibility study was conducted on a random sample of 100 systematic reviews indexed in MEDLINE in November 2021. The primary outcome measure is the percentage of systematic reviews for which all database searches can be reproduced, operationalized as fulfilling six key Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension (PRISMA-S) reporting guideline items and having all database searches reproduced within 10% of the number of original results. Key reporting guideline items included database name, multi-database searching, full search strategies, limits and restrictions, date(s) of searches, and total records. RESULTS: The 100 systematic review articles contained 453 database searches. Only 22 (4.9%) database searches reported all six PRISMA-S items. Forty-seven (10.4%) database searches could be reproduced within 10% of the number of results from the original search; six searches differed by more than 1,000% between the originally reported number of results and the reproduction. Only one systematic review article provided the necessary search details to be fully reproducible. CONCLUSION: Systematic review search reporting is poor. To correct this will require a multifaceted response from authors, peer reviewers, journal editors, and database providers.

The Association between Dietary Inflammatory Potential and Urologic Cancers: A Meta-analysis.

A meta-analysis published in 2018 indicated a significant association between the dietary inflammatory index (DII) and risk of urologic cancers (UC). The number of included studies was limited, and more research has been published on this topic since then. The current study aimed to find a more precise estimate of the association between dietary inflammatory potential and risk of UC by updating the previous meta-analysis. The PubMed and Embase databases were searched between January 2015 and April 2023 to identify eligible articles. Combined relative risk (RR) and 95% confidence intervals (CI) were calculated by random-effects model to assess the association between dietary inflammatory potential and risk of UC by comparison of the highest versus the lowest category of the DII/empirical dietary inflammatory pattern (EDIP) or by using the continuous DII/EDIP score. The analysis, including 23 studies with 557,576 subjects, showed different results for UC. There was a significant association for prostate cancer among case-control studies (RR = 1.75, 95% CI: 1.34-2.28), whereas among cohort studies a null association was found (RR = 1.02, 95% CI: 0.96-1.08). For bladder cancer, a nonsignificant association was observed in both case-control (RR = 1.59, 95% CI: 0.95-2.64) and cohort studies (RR = 1.03, 95% CI: 0.86-1.24). Pooled RR from 3 case-control studies displayed a statistically significant association between the DII and risk of kidney cancer (RR = 1.27, 95% CI: 1.03-1.56). Although DII was positively associated with all types of UC, no association was found for EDIP. The present meta-analysis confirmed that an inflammatory diet has a direct effect on the development of prostate cancer and kidney cancer. Large-scale studies are needed to demonstrate the association between dietary inflammatory potential and risk of UC and provide effective nutritional advice for UC prevention. PROTOCOL REGISTRATION: The protocol was registered in the International Prospective Register of Systematic Reviews (CRD42023391204).

Relationship between multimorbidity, functional limitation, and quality of life among middle-aged and older adults: findings from the longitudinal analysis of the 2013-2020 Survey of Health, Ageing, and Retirement in Europe (SHARE).

PURPOSE: The increased burden of multimorbidity is restricting individuals' ability to live autonomously, leading to a poorer quality of life. This study estimated trajectories of functional limitation and quality of life among middle-aged (ages 50 to 64 years) and older (aged 65 years and older) individuals with and without multimorbidity. We also assessed differences in the relationship between these two trajectories by multimorbidity status and separately for each age cohort. METHODS: Data originated from the Survey of Health, Ageing, and Retirement in Europe (SHARE). In Luxembourg, data were obtained between 2013 and 2020, involving 1,585 respondents ≥ 50 years of age. Multimorbidity was defined as a self-reported diagnosis of two or more out of 16 chronic conditions; functional limitation was assessed by a combined (Instrumental) Activities of Daily Living (ADL/IADLI) scale; and to measure quality of life, we used the Control, Autonomy, Self-Realization, and Pleasure (CASP-12) scale. Latent growth curve modelling techniques were used to conduct the analysis where repeated measures of quality of life and functional limitation were treated as continuous and zero-inflated count variables, respectively. The model was assessed separately in each age cohort, controlling for the baseline covariates, and the estimates from the two cohorts were presented as components of a synthetic cohort covering the life course from the age of 50. RESULTS: Middle-aged and older adults living with multimorbidity experienced poorer quality of life throughout the life course and were at a higher risk of functional limitation than those without multimorbidity. At baseline, functional limitation had a negative impact on quality of life. Furthermore, among middle-aged adults without multimorbidity and older adults with multimorbidity, an increase in the number of functional limitations led to a decline in quality of life. These results imply that the impact of multimorbidity on functional limitation and quality of life may vary across the life course. CONCLUSION: Using novel methodological techniques, this study contributes to a better understanding of the longitudinal relationship between functional limitation and quality of life among individuals with and without multimorbidity and how this relationship changes across the life course. Our findings suggest that lowering the risk of having multimorbidity can decrease functional limitation and increase quality of life.

Determinants of patient-reported functional mobility in people with Parkinson's disease: A systematic review.

BACKGROUND: Information on determinants of patient-reported functional mobility is lacking but would inform the planning of healthcare, resources and strategies to promote functional mobility in people with Parkinson's disease (PD). RESEARCH QUESTION: To identify the determinants of patient-reported functional mobility of people with PD. METHODS: Eligible: Randomized Controlled Trials, cohort, case-control, or cross-sectional analyses in people PD without date or setting restrictions, published in English, German, or French. Excluded: instruments with under 50 % of items measuring mobility. On August 9th 2023 we last searched Medline, CINAHL and PsychInfo. We assessed risk of bias using the mixed-methods appraisal tool. Results were synthesized by tabulating the determinants by outcomes and study designs. RESULTS: Eleven studies published 2012-2023 were included (most in Swedish outpatient settings). Samples ranged from 9 to 255 participants. Follow-up varied from 1.5 to 36 months with attrition of 15-42 %. Heterogenic study designs complicated results synthesis. However, determinants related to environment seem to associate the strongest with patient-reported functional mobility, although determinants related to body structures and functions were most investigated. We identified disease duration, the ability to drive, caregiving, sex, age, cognitive impairment, postural instability and social participation as determinants of patient-reported functional mobility. DISCUSSION: Methodological quality of the studies was limited. No study reported an a priori power calculation. Three studies controlled for confounders. The included studies lack representativeness of the population of people living with PD. Standardized sets of outcomes could enable more systematic research synthesis. CONCLUSIONS: Future research should focus on activities, participation and environmental factors and improve methodological quality.

A predictive model for perinatal hypoxic ischemic encephalopathy using linked maternal and neonatal hospital data.

PURPOSE: To build an evidence-based model to estimate case-specific risk of perinatal hypoxic ischemic encephalopathy. METHODS: A retrospective, cross-sectional study of all births in Hawaii, Michigan, and New Jersey between 2010 and 2015, using linked maternal labor/delivery and neonatal birth records. Stepwise logistic regression and competitive Akaike information criterion were used to identify the most parsimonious model. Predictive ability of the model was measured with bootstrapped optimism-adjusted area under the ROC curve. RESULTS: Among 836,216 births there were 376 (0.45 per 1000) cases of hypoxic ischemic encephalopathy. The final model included 28 variables, 24 associated with increased risk, and 4 that were protective. The optimism-adjusted area under the ROC curve was 0.84. Estimated risk in the study population ranged from 1 in ∼323,000 to 1 in 2.5. The final model confirmed known risk factors (e.g., sentinel events and shoulder dystocia) and identified novel risk factors, such as maternal race and insurance status. CONCLUSION: Our study shows that risk of perinatal hypoxic ischemic encephalopathy injury can be estimated with high confidence. Our model fills a notable gap in the study of hypoxic ischemic encephalopathy prevention: the estimation of risk, particularly in the United States population which is unique with respect to racial and socioeconomic disparities.

The role of multimorbidity and socio-economic characteristics as potential risk factors for Long Covid: evidence from the multilevel analysis of the Survey of Health, Ageing and Retirement in Europe's corona surveys (2020-2021).

BACKGROUND: A substantial proportion of individuals continue experiencing persistent symptoms following the acute stage of their Covid-19 illness. However, there is a shortage of population-based studies on Long Covid risk factors. OBJECTIVE: To estimate the prevalence of Long Covid in the population of middle-aged and older Europeans having contracted Covid-19 and to assess the role of multimorbidity and socio-economic characteristics as potential risk factors of Long Covid. METHODS: A population-based longitudinal prospective study involving a sample of respondents 50 years and older (n = 4,004) from 27 countries who participated in the 2020 and 2021 Survey of Health, Ageing and Retirement in Europe (SHARE), in particular the Corona Surveys. Analyses were conducted by a multilevel (random intercept) hurdle negative binomial model. RESULTS: Overall, 71.6% (95% confidence interval = 70.2-73.0%) of the individuals who contracted Covid-19 had at least one symptom of Long Covid up to 12 months after the infection, with an average of 3.06 (standard deviation = 1.88) symptoms. There were significant cross-country differences in the prevalence of Long Covid and number of symptoms. Higher education and being a man were associated with a lower risk of Long Covid, whilst being employed was associated with a higher risk of having Long Covid. Multimorbidity was associated with a higher number of symptoms and older age was associated with a lower number of symptoms. CONCLUSION: Our results provide evidence on the substantial burden of Long Covid in Europe. Individuals who contracted Covid-19 may require long-term support or further medical intervention, putting additional pressure on national health care systems.

Maternal fatty acid status during pregnancy versus offspring inflammatory markers: a canonical correlation analysis of the MEFAB cohort.

The development of inflammatory lung disorders in children may be related to maternal fatty acid intake during pregnancy. We therefore examined maternal fatty acid (FA) status during pregnancy and its associations with inflammatory markers and lung conditions in the child by analyzing data from the MEFAB cohort using multivariate canonical correlation analysis (CCA). In the MEFAB cohort, 39 different phospholipid FAs were measured in maternal plasma at 16, 22 and 32 weeks of pregnancy, and at day of birth. Child inflammatory markers and self-reported doctor diagnosis of inflammatory lung disorders were assessed at 7 years of age. Using CCA, we found that maternal FA levels during pregnancy were significantly associated with child inflammatory markers at 7 years of age and that Mead acid (20:3n-9) was the most important FA for this correlation. To further verify the importance of Mead acid, we examined the relation between maternal Mead acid levels at the day of birth with the development of inflammatory lung disorders in children at age 7. After stratification for the child's sex, maternal Mead acid levels at day of birth were significantly related with self-reported doctor diagnosis of asthma and lung infections in boys, and bronchitis and total number of lung disorders in girls. Future studies should investigate whether the importance of Mead acid in the relation between maternal FA status and inflammation and lung disorders in the child is due to its role as biomarker for essential fatty acid deficiency or due to its own biological function as pro-inflammatory mediator.

Selenium and Vitamin E for Prevention of Non-Muscle-Invasive Bladder Cancer Recurrence and Progression: A Randomized Clinical Trial.

Importance: Selenium and vitamin E have been identified as promising agents for the chemoprevention of recurrence and progression of non-muscle-invasive bladder cancer. Objective: To determine whether selenium and/or vitamin E may prevent disease recurrence in patients with newly diagnosed NMIBC. Design, Setting, and Participants: This multicenter, prospective, double-blinded, placebo-controlled, 2 × 2 factorial randomized clinical trial included patients with newly diagnosed NMIBC recruited from 10 secondary or tertiary care hospitals in the UK. A total of 755 patients were screened for inclusion; 484 did not meet the inclusion criteria, and 1 declined to participate. A total of 270 patients were randomly assigned to 4 groups (selenium plus placebo, vitamin E plus placebo, selenium plus vitamin E, and placebo plus placebo) in a double-blind fashion between July 17, 2007, and October 10, 2011. Eligibility included initial diagnosis of NMIBC (stages Ta, T1, or Tis); randomization within 12 months of first transurethral resection was required. Interventions: Oral selenium (200 µg/d of high-selenium yeast) and matched vitamin E placebo, vitamin E (200 IU/d of d-alfa-tocopherol) and matched selenium placebo, selenium and vitamin E, or placebo and placebo. Main Outcome and Measures: Recurrence-free interval (RFI) on an intention-to-treat basis (analyses completed on November 28, 2022). Results: The study randomized 270 patients (mean [SD] age, 68.9 [10.4] years; median [IQR] age, 69 [63-77] years; 202 male [75%]), with 65 receiving selenium and vitamin E placebo, 71 receiving vitamin E and selenium placebo, 69 receiving selenium and vitamin E, and 65 receiving both placebos. Median overall follow-up was 5.5 years (IQR, 5.1-6.1 years); 228 patients (84%) were followed up for more than 5 years. Median treatment duration was 1.5 years (IQR, 0.9-2.5 years). The study was halted because of slow accrual. For selenium (n = 134) vs no selenium (n = 136), there was no difference in RFI (hazard ratio, 0.92; 95% CI, 0.65-1.31; P = .65). For vitamin E (n = 140) vs no vitamin E (n = 130), there was a statistically significant detriment to RFI (hazard ratio, 1.46; 95% CI, 1.02-2.09; P = .04). No significant differences were observed for progression-free interval or overall survival time with either supplement. Results were unchanged after Cox proportional hazards regression modeling to adjust for known prognostic factors. In total, 1957 adverse events were reported; 85 were serious adverse events, and all were considered unrelated to trial treatment. Conclusions and Relevance: In this randomized clinical trial of selenium and vitamin E, selenium supplementation did not reduce the risk of recurrence in patients with NMIBC, but vitamin E supplementation was associated with an increased risk of recurrence. Neither selenium nor vitamin E influenced progression or overall survival. Vitamin E supplementation may be harmful to patients with NMIBC, and elucidation of the underlying biology is required. Trial Registration: isrctn.org Identifier: ISRCTN13889738.