Transcriptome-wide association study and Mendelian randomization in pancreatic cancer identifies susceptibility genes and causal relationships with type 2 diabetes and venous thromboembolism.

BACKGROUND: Two important questions regarding the genetics of pancreatic adenocarcinoma (PDAC) are 1. Which germline genetic variants influence the incidence of this cancer; and 2. Whether PDAC causally predisposes to associated non-malignant phenotypes, such as type 2 diabetes (T2D) and venous thromboembolism (VTE). METHODS: In this study of 8803 patients with PDAC and 67,523 controls, we first performed a large-scale transcriptome-wide association study to investigate the association between genetically determined gene expression in normal pancreas tissue and PDAC risk. Secondly, we used Mendelian Randomization (MR) to analyse the causal relationships among PDAC, T2D (74,124 cases and 824,006 controls) and VTE (30,234 cases and 172,122 controls). FINDINGS: Sixteen genes showed an association with PDAC risk (FDR <0.10), including six genes not yet reported for PDAC risk (PPIP5K2, TFR2, HNF4G, LRRC10B, PRC1 and FBXL20) and ten previously reported genes (INHBA, SMC2, ABO, PDX1, MTMR6, ACOT2, PGAP3, STARD3, GSDMB, ADAM33). MR provided support for a causal effect of PDAC on T2D using genetic instruments in the HNF4G and PDX1 loci, and unidirectional causality of VTE on PDAC involving the ABO locus (OR 2.12, P < 1e-7). No evidence of a causal effect of PDAC on VTE was found. INTERPRETATION: These analyses identified candidate susceptibility genes and disease relationships for PDAC that warrant further investigation. HNF4G and PDX1 may induce PDAC-associated diabetes, whereas ABO may induce the causative effect of VTE on PDAC. FUNDING: National Institutes of Health (USA).

Circulating Metabolite Profiles and Risk of Coronary Heart Disease Among Racially and Geographically Diverse Populations.

BACKGROUND: Metabolomics may reveal novel biomarkers for coronary heart disease (CHD). We aimed to identify circulating metabolites and construct a metabolite risk score (MRS) associated with incident CHD among racially and geographically diverse populations. METHODS: Untargeted metabolomics was conducted using baseline plasma samples from 900 incident CHD cases and 900 age-/sex-/race-matched controls (300 pairs of Black Americans, White Americans, and Chinese adults, respectively), which detected 927 metabolites with known identities among ≥80% of samples. After quality control, 896 case-control pairs remained and were randomly divided into discovery (70%) and validation (30%) sets within each race. In the discovery set, conditional logistic regression and least absolute shrinkage and selection operator over 100 subsamples were applied to identify metabolites robustly associated with CHD risk and construct the MRS. The MRS-CHD association was evaluated using conditional logistic regression and the C-index. Mediation analysis was performed to examine if MRS mediated associations between conventional risk factors and incident CHD. The results from the validation set were presented as the main findings. RESULTS: Twenty-four metabolites selected in ≥90% of subsamples comprised the MRS, which was significantly associated with incident CHD (odds ratio per 1 SD, 2.21 [95% CI, 1.62-3.00] after adjusting for sociodemographics, lifestyles, family history, and metabolic health status). MRS could distinguish incident CHD cases from matched controls (C-index, 0.69 [95% CI, 0.63-0.74]) and improve CHD risk prediction when adding to conventional risk factors (C-index, 0.71 [95% CI, 0.65-0.76] versus 0.67 [95% CI, 0.61-0.73]; P<0.001). The odds ratios and C-index were similar across subgroups defined by race, sex, socioeconomic status, lifestyles, metabolic health, family history, and follow-up duration. The MRS mediated large portions (46.0%-74.2%) of the associations for body mass index, smoking, diabetes, hypertension, and dyslipidemia with incident CHD. CONCLUSIONS: In a diverse study sample, we identified 24 circulating metabolites that, when combined into an MRS, were robustly associated with incident CHD and modestly improved CHD risk prediction beyond conventional risk factors.

The Association Between Psoriasis and Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analysis of Observational Studies.

Psoriasis is a chronic immune-mediated disease affecting the skin, nails, and/or joints. It is associated with systemic inflammation and may also be linked to an increased risk of atherosclerotic cardiovascular disease (ASCVD). The objectives of this study were to determine the overall risk of ASCVD in patients with psoriasis and to evaluate the risk according to ASCVD type and the severity of psoriasis. This was a systematic review and meta-analysis of observational studies reporting the association between psoriasis and one or more of the clinical types of ASCVD. We searched Medical Literature Analysis and Retrieval System Online (MEDLINE) via PubMed, Excerpta Medica Database (EMBASE), Scopus, Bielefeld Academic Search Engine (BASE), and Google Scholar for relevant studies in the English language from the beginning of their records to July 2023. Study selection and data extraction were conducted by four independent reviewers. A total of 21 observational studies (three cross-sectional, one case-control, and 17 cohort) were included in this review, representing a total of 778,049 patients with psoriasis and 16,881,765 control subjects without psoriasis. The included studies had varying degrees of covariate adjustment, and thus, their findings may have been subject to residual confounding. All the meta-analyses used the adjusted effect sizes and were based on the random-effects model. However, the cohort studies were analysed separately from the non-cohort studies (the case-control and cross-sectional studies). There was a significant association between psoriasis and ASCVD (cohort studies: hazard ratio (HR), 1.21; 95% confidence interval (CI), 1.14 to 1.28; I2 = 63%; p < 0.001; non-cohort studies: odds ratio (OR), 1.60; 95% CI, 1.34 to 1.92; I2 = 31%; p = 0.23). Psoriasis was also significantly associated with myocardial infarction (cohort studies: HR, 1.20; 95% CI, 1.10 to 1.31; I2 = 60%; p < 0.001; non-cohort studies: OR, 1.57; 95% CI, 1.15 to 2.15; I2 = 74%; p = 0.05), coronary artery disease (cohort studies: HR, 1.20; 95% CI, 1.13 to 1.28; I2 = 67%; p < 0.001; non-cohort studies: OR, 1.60; 95% CI, 1.34 to 1.92; I2 = 31%; p = 0.23), aortic aneurysm (HR, 1.45; 95% CI, 1.04 to 2.02; I2 = 67%; p = 0.08) but not with ischaemic stroke (HR, 1.14; 95% CI, 0.96 to 1.36; I2 = 44%; p = 0.17). Pooled analysis in terms of the severity of psoriasis showed that both mild (cohort studies: HR, 1.17; 95% CI, 1.08 to 1.26; I2 = 74%; p < 0.001; non-cohort studies: OR, 1.54; 95% CI, 1.25 to 1.90; I2 = 0%; p = 0.50) and severe (cohort studies: HR, 1.43; 95% CI, 1.23 to 1.65; I2 = 65%; p < 0.001; non-cohort studies: OR, 1.65; 95% CI, 1.29 to 2.12; I2 = 25%; p = 0.26) psoriasis were significantly associated with ASCVD. Psoriasis (including mild and severe disease) is associated with an increased risk of ASCVD, including coronary artery disease (CAD) and aortic aneurysm (AA). ASCVD risk assessment and prevention should be prioritised in all adult psoriasis patients. Future observational studies investigating the association between psoriasis and ASCVD should conduct a more comprehensive adjustment of covariates.

Childhood asthma and mould in homes-A meta-analysis.

Asthma is a multifaceted and multicausal disease. Childhood asthma is strongly influenced by genetic traits and is characterized by hyperreactivity of the airways so that also unspecific triggers including moulds can trigger an asthma attack. Therefore, it is undisputed that moulds in the home can cause asthma attacks in asthmatic children. It is, however, unclear if mould in homes also induce the development of asthma. Because more and more severe attacks in asthmatic children living in mouldy homes might speed up the diagnosis of asthma, cross-sectional studies are not well-suited to differentiate between mould as a causative or only as a precipitating factor. Cross-sectional studies show an increased asthma risk and poorer lung function in children living in mouldy homes. To better understand the causal role of mould in homes, a systematic review was performed with random effects meta-analysis focusing on cohort and case-control studies only.We found 21 case-control and 11 cohort studies examining the association between mould at home and later advent of childhood asthma. According to the case-control studies, mouldy homes increase the risk of asthma by 53% (95 confidence interval [CI]: 42-65%) with no evidence of heterogeneity or publication bias. Risk estimates based on cohort studies were smaller with 15% (1-31%). The cohort studies also showed no publication bias but substantial heterogeneity (I2 = 60.5, p = 0.005). Heterogeneity could be partly explained by percentage of male children, age of participants, and publication year, but was not affected by study quality.In conclusion, living in mouldy homes during childhood seems to increase the risk of later developing bronchial asthma.

Healthcare-seeking behavior preceding diagnosis of Lyme neuroborreliosis: population-based nationwide matched nested case-control study.

OBJECTIVES: To identify diagnostic opportunities, we investigated healthcare-seeking behavior among patients with Lyme neuroborreliosis (LNB) within 28 weeks before diagnosis. METHODS: We conducted a population-based, nationwide matched nested case-control study (Denmark, 2009-2021). As cases, we included all Danish residents with LNB (positive Borrelia burgdorferi intrathecal antibody index test and cerebrospinal fluid pleocytosis). We randomly selected controls from the general population, matched 10:1 on date of birth and sex. Exposures were assignment of diagnostic codes for symptoms, contact to medical specialties, medical wandering, and undergoing diagnostic procedures. We calculated the weekly and 3-months proportion of individuals with exposures and calculated absolute risk differences with corresponding 95% confidence intervals (95%CI). RESULTS: We included 1,056 cases with LNB and 10,560 controls. Within 3 months before diagnosis, the most frequent assigned symptoms were pain (difference: 13.0%, 95%CI: 10.9-15.1). Cases with LNB exhibited increased contact to most specialties, particularly general practitioners (difference: 48.7%, 95%CI: 46.0-51.4), neurology (difference: 14.3%, 95%CI: 11.7-16.8), and internal medicine (difference: 11.1%, 95%CI: 8.7-13.5), and medical wandering (difference: 17.1%, 95%CI: 14.3-20.0). Common diagnostic procedures included imaging of the brain (difference: 10.2, 95%CI: 8.3-12.1), the spine (difference: 8.8%, 85%CI: 7.0-10.6), and the abdomen (difference: 7.2%, 95%CI: 5.4-9.1). The increase in healthcare-seeking behavior was observed up to 12 weeks preceding diagnosis. CONCLUSIONS: Pain appears to be an ambiguous symptom of LNB, potentially contributing to delays in establishing the correct diagnosis. It would be difficult to identify patients with LNB more effectively as the increased healthcare-seeking behavior preceding diagnosis is distributed across many medical specialties.

Breastfeeding Duration Reduces the Risk of Childhood Leukemia and Modifies the Risk of Developing Functional Gastrointestinal Disorders.

Objective: The aim of this study was to test the hypothesis that the duration of breastfeeding in infancy reduces the risk of childhood leukemia or lymphoma, and modifies the risk of developing functional gastrointestinal disorders (FGIDs). Subjects and Methods: This case-control study involved the recruitment of children with lymphoid malignancy and functional gastrointestinal symptoms with healthy children as controls. Focused questionnaires were used to collect data on breastfeeding history and other key risk factors. Univariate and multivariate analyses were undertaken. Results: Of the 334 children with lymphoid malignancy, 65% were male. The control group included 334 age- and sex-matched participants. Most (n = 189; 56.6%) of the children with leukemia were <10 years of age. Differences between cases and controls included the duration of breastfeeding (p < 0.0001), mean birthweight (p < 0.001), maternal age (p < 0.001), paternal age (p < 0.001), birth order (p < 0.001), mean number of children (p < 0.001), BMI percentile (p = 0.042), and maternal smoking (p = 0.012). Breastfeeding duration of up to 6 months' duration, when compared with feeding of longer than 6 months, was associated with increased odds ratios (OR) for acute lymphoblastic leukemia (OR = 3.43, 95% confidence interval [CI] 2.37-4.98; p < 0.001), Hodgkin's lymphoma (OR = 1.58, 95% CI: 0.88-2.84, p = 0.120), Non-Hodgkin's lymphoma (OR = 2.14, 95% CI: 1.25-3.65, p = 0.005), and overall (OR = 1.95, 95% CI: 1.40-2.71, p < 0.001). Cases also differed from controls with regard to FGIDs, such as stomach ache (p < 0.001), dyspepsia (p < 0.001), early satiety (p = 0.017), bowel satisfaction (p < 0.001), bloating (p < 0.001), nausea (p = 0.005), vomiting (p = 0.039), constipation (p = 0.003), diarrhea (p = 0.010), gastrointestinal canal congestion (p =0.039), muscle aches pains (p = 0.008), fecal incontinence (p = 0.021), and indigestion (p = 0.003). A multivariate stepwise regression analysis revealed that maternal smoking (p < 0.001), formula feeding (p < 0.001), duration of breastfeeding (p < 0.001), birth order (p = 0.002), mother's age (p = 0.004) and the child's birthweight (p = 0.009) were predictors for leukemia. Further analysis showed that dyspepsia (p < 0.001), gastrointestinal tract canal congestion (p < 0.001), constipation (p = 0.009), diarrhea (p = 0.013), bowel satisfaction (p = 0.021), bloating (p = 0.022), duration of breastfeeding (p < 0.001), and stomach ache (p = 0.025) were significant predictors for developing FGID symptoms after adjusting for age, gender, and other confounding variables. Conclusion: This study confirmed that breastfeeding has some effect on reducing possible risk of childhood lymphoma and leukemia and FGID symptoms compared with healthy control children.

Female sexual function in long-term cervical cancer survivors compared with healthy women and women affected by benign gynecological disorders.

OBJECTIVE: To compare the female sexual function between cervical cancer survivors and healthy women or with benign gynecological diseases. STUDY DESIGN: From January 1, 2010 to January 31, 2019, a case-control study was conducted to compare the female sexual function of 106 cervical cancer survivors from a tertiary hospital and 185 women admitted to a gynecological outpatient clinic from the same health area for a routine gynecological examination (n=46) or for a benign gynecological disorder (symptomatic, n=113; asymptomatic, n=26). We prospectively assessed the female sexual function using the Female Sexual Function Index (FSFI). For the contrastive analysis hypothesis, we employed R statistical software. RESULTS: Cervical cancer survivors reported lower sexual activity rates than controls, in general, did (47.12% vs. 88.65%, p=0.0001), and, particularly, compared with healthy and symptomatic controls (47.12% vs. 82.61%, p=0.003; 47.12% vs. 87.61%, p=0.0001, respectively). Sixty and fifty-eight hundredths percent of the cervical cancer survivors experienced female sexual dysfunction, mainly due to hypoactive sexual desire (93.27%). Female sexual dysfunction was diagnosed in 64.32% of the controls, with sexual arousal disorders being the most common diagnosis (44.86%). Compared with controls, cervical cancer survivors exhibited considerably lower FSFI total scores and in sexual desire and lubrication domains (p <0.000; p <0.0001; p=0.023). CONCLUSIONS: Cervical cancer survivors had worse female sexual function and less sexual activity than controls did, although scores in both groups were in range of FSD. Rates of female sexual dysfunction were similar across cervical cancer survivors and controls, with hypoactive sexual desire and sexual arousal disorders as the most common diagnoses, respectively.

Genetic polymorphisms of inflammatory and bone metabolism related proteins in a population with dental implants of the Basque Country. A case-control study.

BACKGROUND: Peri-implantitis (PI) is a frequent inflammatory disorder characterised by progressive loss of the supporting bone. Not all patients with recognised risk factors develop PI. The aim of this study is to evaluate the presence of single nucleotide polymorphisms (SNP) of inflammatory and bone metabolism related proteins in a population treated with dental implants from the Basque Country (Spain). METHODS: We included 80 patients with diagnosis of PI and 81 patients without PI, 91 women and 70 men, with a mean age of 60.90 years. SNPs of BMP-4, BRINP3, CD14, FGF-3, FGF-10, GBP-1, IL-1α, IL-1ß, IL-10, LTF, OPG and RANKL proteins were selected. We performed a univariate and bivariate analysis using IBM SPSS® v.28 statistical software. RESULTS: Presence of SNPs GBP1 rs7911 (p = 0.041) and BRINP3 rs1935881 (p = 0.012) was significantly more common in patients with PI. Patients with PI who smoked (> 10 cig/day) showed a higher presence of OPG rs2073617 SNP (p = 0.034). Also, BMP-4 rs17563 (p = 0.018) and FGF-3 rs1893047 (p = 0.014) SNPs were more frequent in patients with PI and Type II diabetes mellitus. CONCLUSIONS: Our findings suggest that PI could be favoured by an alteration in the osseointegration of dental implants, based on an abnormal immunological response to peri-implant infection in patients from the Basque Country (Spain).

Nirsevimab Effectiveness Against Cases of Respiratory Syncytial Virus Bronchiolitis Hospitalised in Paediatric Intensive Care Units in France, September 2023-January 2024.

In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory syncytial virus (RSV). Using data from a network of paediatric intensive care units (PICUs), we aimed to estimate nirsevimab effectiveness against severe cases of RSV bronchiolitis in France. We conducted a case-control study based on the test-negative design and included 288 infants reported by 20 PICUs. We estimated nirsevimab effectiveness at 75.9% (48.5-88.7) in the main analysis and 80.6% (61.6-90.3) and 80.4% (61.7-89.9) in two sensitivity analyses. These real-world estimates confirmed the efficacy observed in clinical studies.

Assessing the risks for stillbirth in São Paulo, Brazil: protocol for a multidisciplinary case-control study - FetRisks.

Stillbirth is a fundamental component of childhood mortality, but its causes are still insufficiently understood. This study aims to explore stillbirth risk factors by using a multidisciplinary approach to stimulate public policies and protocols to prevent stillbirth, improve maternal care and support bereaved families. METHODS AND ANALYSIS: In this case-control study with stillbirths and live births in 14 public hospitals in São Paulo, mothers are interviewed at hospitals after delivery, and hospital records and prenatal care registries are reviewed. Maternal and umbilical cord blood samples and placentas are collected to analyse angiogenesis and infection biomarkers, and the placenta's anatomopathological exam. Air pollutant exposure is estimated through the participant's residence and work addresses. Traditional and non-invasive autopsies by image-guided histopathology are conducted in a subset of stillbirths. Subsample mothers of cases are interviewed at home 2 months after delivery on how they were dealing with grief. Information contained in the official prenatal care registries of cases and controls is being compiled. Hospital managers are interviewed about the care offered to stillbirth mothers. Data analysis will identify the main risk factors for stillbirth, investigate their interrelations, and evaluate health services care and support for bereaved families. We hope this project will contribute to the understanding of stillbirth's risk factors and related health services in Brazil, providing new knowledge about this central public health problem, contributing to the improvement of public policies and prenatal and puerperal care, helping to prevent stillbirths and improve the healthcare and support for bereaved families. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the Municipal Health Secretary (process no 16509319.0.3012.5551) and of the Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (process no 16509319.0.0000.0068). Results will be communicated to the study participants, policy-makers and the scientific community.

History and Familial Aggregation of Immune-Mediated Diseases in Sarcoidosis: A Register-Based Case-Control Family Study.

BACKGROUND: An autoimmune component in the cause of sarcoidosis long has been debated, but population-based data on the clustering of immune-mediated diseases (IMDs) and sarcoidosis in individuals and families suggestive of shared cause is limited. RESEARCH QUESTION: Do patients with a history of IMDs have a higher risk of sarcoidosis and do IMDs cluster in families with sarcoidosis? STUDY DESIGN AND METHODS: We conducted a case-control family study (2001-2020). Patients with sarcoidosis (N = 14,146) were identified in the Swedish National Patient Register using a previously validated definition (≥ 2 International Classification of Diseases [ICD]-coded inpatient or outpatient visits). At diagnosis, patients were matched to up to 10 control participants from the general population (N = 118,478) for birth year, sex, and residential location. Patients, control participants, and their first-degree relatives (FDRs; Multi-Generation Register) were ascertained for IMDs by means of ICD codes in the Patient Register (1968-2020). Conditional logistic regression was used to estimate ORs and 95% CIs of sarcoidosis associated with a history of IMDs in patients and control participants and in FDRs. RESULTS: Patients with sarcoidosis exhibited a higher prevalence of IMDs compared with control participants (7.7% vs 4.7%), especially connective tissue diseases, cytopenia, and celiac disease. Familial aggregation was observed across IMDs; the strongest association was with celiac disease (OR, 2.09; 95% CI, 1.22-3.58), followed by cytopenia (OR, 1.88; 95% CI, 0.97-3.65), thyroiditis (OR, 1.72; 95% CI, 1.14-2.60), skin psoriasis (OR, 1.70; 95% CI, 1.34-2.15), inflammatory bowel disease (OR, 1.53; 95% CI, 1.14-2.03), immune-mediated arthritis (OR, 1.49; 95% CI, 1.20-1.85), and connective tissue disease (OR, 1.39; 95% CI, 1.00-1.93). INTERPRETATION: IMDs confer a higher risk of sarcoidosis and they aggregate in families with sarcoidosis, signaling a shared cause between IMDs and sarcoidosis. Our findings warrant further evaluation of shared genetic mechanisms.

Association of Gout with Head and Neck Cancer: Longitudinal Follow-Up Studies Using a National Health Insurance Database in South Korea.

Objective: Previous studies have reported controversial results on the association between gout and the risk of cancer. This study aimed to investigate the relationship between gout and the incidence of head and neck cancer (HNC). Methods: The data of participants who underwent health checkups in 2009 were analyzed using the National Health Insurance Database in South Korea. A total of 14,348 HNC patients and 57,392 control participants were analyzed for a prior history of gout. Overlap weighting was applied, and odds ratios (ORs) of gout for HNC patients were analyzed. The overlap-weighted model adjusted for demographic, socioeconomic, and lifestyle factors and comorbidities. HNC sites were classified as oral cavity cancer, oropharyngeal cancer, nasopharyngeal cancer, hypopharyngeal cancer, nasal cavity/sinus cancer, larynx cancer, or salivary gland cancer, and the ORs of gout were estimated for each site. Results: Overall, patients with HNC had 1.12-fold greater odds of having gout (95% confidence intervals [CIs] = 1.04-1.20). According to the site of HNC, oral cavity cancer, oropharynx cancer, and larynx cancer demonstrated high odds of having gout (OR = 1.25, 95% CI = 1.16-1.34 for oral cavity cancer; OR = 1.08, 95% CI = 1.01-1.15 for oropharynx cancer; and OR = 1.12, 95% CI = 1.06-1.20 for larynx cancer). On the other hand, nasal cavity/sinus cancer, nasopharynx cancer, and salivary gland cancer presented low odds of having gout (OR = 0.78, 95% CI = 0.72-0.84 for nasal cavity/sinus cancer; OR = 0.89, 95% CI = 0.83-0.96 for nasopharynx cancer; and OR = 0.88, 95% CI = 0.81-0.96 for salivary gland cancer). Conclusions: A prior history of gout was associated with a high overall incidence of HNC. Oral cavity cancer, oropharynx cancer, and larynx cancer have a high incidence in gout patients. However, nasal cavity/sinus cancer, nasopharyngeal cancer, and salivary gland cancer have low incidences in gout patients. The impact of gout on HNC risk should be specifically considered according to the site of the HNC.

penalizedclr: an R package for penalized conditional logistic regression for integration of multiple omics layers.

BACKGROUND: The matched case-control design, up until recently mostly pertinent to epidemiological studies, is becoming customary in biomedical applications as well. For instance, in omics studies, it is quite common to compare cancer and healthy tissue from the same patient. Furthermore, researchers today routinely collect data from various and variable sources that they wish to relate to the case-control status. This highlights the need to develop and implement statistical methods that can take these tendencies into account. RESULTS: We present an R package penalizedclr, that provides an implementation of the penalized conditional logistic regression model for analyzing matched case-control studies. It allows for different penalties for different blocks of covariates, and it is therefore particularly useful in the presence of multi-source omics data. Both L1 and L2 penalties are implemented. Additionally, the package implements stability selection for variable selection in the considered regression model. CONCLUSIONS: The proposed method fills a gap in the available software for fitting high-dimensional conditional logistic regression models accounting for the matched design and block structure of predictors/features. The output consists of a set of selected variables that are significantly associated with case-control status. These variables can then be investigated in terms of functional interpretation or validation in further, more targeted studies.

Nosocomial outbreak caused by disinfectant-resistant Serratia marcescens in an adult intensive care unit, Hungary, February to March 2022.

In 2022, an outbreak with severe bloodstream infections caused by Serratia marcescens occurred in an adult intensive care unit (ICU) in Hungary. Eight cases, five of whom died, were detected. Initial control measures could not stop the outbreak. We conducted a matched case-control study. In univariable analysis, the cases were more likely to be located around one sink in the ICU and had more medical procedures and medications than the controls, however, the multivariable analysis was not conclusive. Isolates from blood cultures of the cases and the ICU environment were closely related by whole genome sequencing and resistant or tolerant against the quaternary ammonium compound surface disinfectant used in the ICU. Thus, S. marcescens was able to survive in the environment despite regular cleaning and disinfection. The hospital replaced the disinfectant with another one, tightened the cleaning protocol and strengthened hand hygiene compliance among the healthcare workers. Together, these control measures have proved effective to prevent new cases. Our results highlight the importance of multidisciplinary outbreak investigations, including environmental sampling, molecular typing and testing for disinfectant resistance.

Cognitive performance in adults with post-COVID syndrome: Results from a German case-control study.

Numerous studies on post-COVID syndrome (PCS) describe persisting symptoms of cognitive impairment. Previous studies, however, often investigated small samples or did not assess covariates possibly linked to cognitive performance. We aimed to describe 1) global and domain-specific cognitive performance in adults with PCS, controls with previous SARS-CoV-2 infection and healthy controls, 2) associations of sociodemographics, depressive symptoms, anxiety, fatigue, somatic symptoms and stress with cognitive performance and subjective cognitive decline (SCD), using data of the LIFE-Long-COVID-Study from Leipzig, Germany. Group differences in cognitive performance and associations with sociodemographic and neuropsychiatric covariates were assessed using multivariable regression analyses. Our study included n = 561 adults (Mage: 48.8, SD: 12.7; % female: 70.6). Adults with PCS (n = 410) performed worse in tests on episodic memory (b = -1.07, 95 % CI: -1.66, -0.48) and visuospatial abilities (b = -3.92, 95 % CI: -6.01, -1.83) compared to healthy controls (n = 64). No impairments were detected for executive function, verbal fluency, and global cognitive performance. Odds of SCD were not higher in PCS. A previous SARS-CoV-2 infection without PCS (n = 87) was not linked to cognitive impairment. Higher age and higher levels of stress and fatigue were linked to worse performance in several cognitive domains. Routine administration of tests for episodic memory and visuospatial abilities might aid in the identification of individuals at risk for cognitive impairment when reporting symptoms of PCS. Low numbers of participants with severe COVID-19 infections possibly limit generalizability of our findings.

Determinants of puerperal sepsis among postpartum women: a case-control study in East Shoa Zone public hospitals, Central Ethiopia.

OBJECTIVE: To identify determinants of puerperal sepsis among postpartum women attending East Shoa Zone public hospitals, Central Ethiopia, 2023. DESIGN AND SETTING: An institutional-based, unmatched case-control study was conducted from 19 June 2023 to 4 September 2023, in East Shoa Zone public hospitals. PARTICIPANTS: 495 postpartum women (100 cases and 395 controls) were selected using systematic sampling techniques. Data were collected through face-to-face interviews and from medical charts using a pretested, structured questionnaire. The AOR with its corresponding 95% CI was used to identify determinant variables. Findings were presented in texts and tables. OUTCOME MEASURES: The medical charts of participants were reviewed to identify those who had developed puerperal sepsis. RESULTS: Anaemia (AOR 6.05; 95% CI 2.57 to 14.26), undernourishment (AOR 4.43; 95% CI 1.96 to 10.01), gestational diabetes mellitus (AOR 3.26; 95% CI 1.22 to 8.74), postpartum haemorrhage (AOR 3.17; 95% CI 1.28 to 7.87), obstructed labour (AOR 2.76; 95% CI 1.17 to 6.52), multiparity (AOR 2.54; 95% CI 1.17 to 5.50), placenta previa (AOR 2.27; 95% CI 1.11 to 4.67) and vaginal examination ≥5 times (AOR 2.19; 95% CI 1.05 to 4.54) were the independent determinants of puerperal sepsis in this study. CONCLUSION: This study found that gestational diabetes mellitus, anaemia, undernourishment, placenta previa, obstructed labour, postpartum haemorrhage and five or more per-vaginal examinations during labour were the determinants of puerperal sepsis. Therefore, it is recommended that obstetric care providers strictly adhere to guidelines on the number of vaginal exams that should be performed throughout labour and that they perform these exams using the appropriate infection-prevention techniques. In addition, they should provide comprehensive health education on nutrition during pregnancy and postnatal periods and the importance of iron supplements.

Statins for neuroprotection in spontaneous intracerebral haemorrhage (STATIC): protocol for a multicentre, prospective and randomised controlled trial.

INTRODUCTION: Intracerebral haemorrhage (ICH) is a neurological emergency with high morbidity and mortality, and current treatment is limited. Emerging evidence has reported that statins can exert neuroprotective effects in cerebrovascular diseases. However, most of the published clinical studies are retrospective. Therefore, it is important to conduct a prospective randomised controlled trial to further validate the efficacy and safety of statins in patients with ICH. METHODS AND ANALYSIS: The present study is performed at Xuan Wu Hospital Capital Medical University, Beijing Fengtai You'anmen Hospital and Shunping County Hospital, Hebei Province. The target number of patients is 98. Eligible patients are randomly assigned in a 1:1 ratio to the statins group or the control group. The primary outcome is the perihaemorrhagic oedema to haematoma ratio at 7 days. Secondary outcomes include mortality at 30 days, haematoma resolution rate at 7 days, National Institute of Health stroke scale (NIHSS) score at 7 days or discharge, ordinal distribution of modified Rankin scale (mRS) score at 90 days, the proportion of patients with an mRS score of 0-2 on day 90, the proportion of patients with an mRS score of 0-3 on day 90, absolute haematoma volume changes between initial and 7-day follow-up CT scan, absolute perihaematomal oedema changes between initial and 7-day follow-up CT scan. ETHICS AND DISSEMINATION: The trial has been approved by the ethics committees of Xuan Wu Hospital Capital Medical University, Beijing Fengtai You'anmen Hospital and Shunping County Hospital, Hebei Province. The results will be disseminated in a peer-reviewed journal and in conference reports. TRIAL REGISTRATION NUMBER: NCT04857632.

Research Review: Social cognition and everyday social skills in children and adolescents with attention-deficit/hyperactivity disorder: a meta-analysis of case-control studies.

BACKGROUND: Previous studies that have assessed social cognition in Attention-Deficit/Hyperactivity Disorder (ADHD) have produced inconsistent findings. To summarize these data and shed light upon moderators that may explain observed inconsistencies, we conducted a systematic review and meta-analysis exploring social cognition (Theory of Mind (ToM), Empathy, Facial and Non-Facial Emotion Recognition) and Everyday Social Skills in children and adolescents with ADHD. METHODS: The current meta-analysis involved 142 studies including 652 effect sizes. These studies compared children and adolescents with ADHD (n = 8,300) and with typical development (n = 7,983). RESULTS: Participants with ADHD exhibited moderate to very large deficits in ToM (SMD = 0.84, 95% CI = 0.68-0.99), Facial Emotion Recognition (SMD = 0.63, 95% CI = 0.46-0.81), and Everyday Social Skills (SMD = 1.23, 95% CI = 1.08-1.37). The magnitude of these impairments was similar when considering effect sizes adjusted for some covariates and the methodological quality of the studies. Few studies have investigated Empathy and Non-Facial Emotion Recognition, which precludes definitive conclusions. CONCLUSIONS: Children and adolescents with ADHD experience robust impairments in ToM, Facial Emotion Recognition and Everyday Social Skills. Future studies should explore whether these deficits are a consequence of difficulties in other areas of cognition (e.g., executive functioning). We have made all our raw data open access to facilitate the use of the present work by the community (e.g., clinicians looking for tools, assessing social impairments, or researchers designing new studies).

[Food consumption patterns and risk of gallstone disease (GD): Case and Control Study in Rosario Argentina.] / Patrones de consumo alimentario y riesgo de enfermedad colelitiásica (EC): Estudio de Casos y Controles en Rosario Argentina.

Introduction: Nutritional exposure is considered the main environmental influence that contributes to gallstone disease (GD). Aim: The aim of this study was to determine food intakes patters and estimate risk of GD. Methods: A nested case-control study was carried out within the framework of a previous screening study conducted on a representative sample in Rosario, Argentina. Participants underwent a personal interview. Average amount of each food intake and quantity nutrients were estimated applying a food-frequency questionnaire. Food consumption patterns were identified by principal component analysis, and logistic regression analysis was used to estimate risks. Results: The sample was conformed by 51 cases and 69 controls. Two dietary patterns were identified. Cases were characterised by the unhealthy intake pattern (high intakes of animal fats, sugar, cereals, grains, cold cuts, processed meats, chicken with skin, fat beef and low intake of red vegetables and yellows, cabbages, fruits and fish). Conclusion: Controls were characterised by the healthy intake pattern (high intake of skinless chicken, nuts, lean beef, vitamin A and C rich fruits, and low consumption of chicken with skin, green leaves vegetables and sprouts). The unhealthy pattern showed an increased risk of developing GD while healthy patter behaved as a protective factor.

Introducción: La exposición nutricional se considera la principal exposición ambiental que contribuye a la formación de cálculos biliares. Objetivo: El objetivo de este trabajo fue determinar el patrón de consumo alimentario de casos y controles de EC y estimar el riesgo de desarrollar la enfermedad según los distintos patrones constituidos. Métodos: Se llevó a cabo un estudio analítico retrospectivo transversal de casos y controles, anidado a un estudio de prevalencia realizado en Rosario. Todos los participantes fueron entrevistados personalmente. El consumo de alimentos se consignó a través de un cuestionario semi-cuantitativo de frecuencia de consumo. Para determinar patrones de consumo alimentario se realizó un análisis de componentes principales, y análisis de regresión logística múltiple para evaluar riesgos. Resultados: La muestra quedó conformada por 51 casos y 69 controles. Se determinaron dos componentes que permitían diferenciar los casos de los controles, a través de las cuales se establecieron 2 patrones de consumo. Los casos se caracterizaron por un consumo determinado por el Patrón Poco saludable (altas ingestas de grasas animales, azúcar, cereales, granos, fiambres y embutidos) y los controles por el consumo del patrón Saludable (altas ingestas de pollo sin piel, frutas secas, carne vacuna magra, frutas, lácteos enteros). El patrón Poco saludable, aumentó el riesgo de desarrollar EC mientras que el patrón Saludable, se comportó como protector. Conclusión principal: Los patrones constituidos diferencian los casos de los controles, y la ingesta propia de los casos se correlaciona con un perfil de consumo que caracteriza a las culturas occidentales modernas y urbanas.

Fatigue in rheumatoid arthritis patients: The status, independent risk factors, and consistency of multiple scales.

INTRODUCTION: Fatigue is a common symptom that negatively affects the outcomes and functions of rheumatoid arthritis (RA) patients. This study aimed to assess the fatigue by two scales and validate their consistency, also to comprehensively evaluate fatigue-related risk factors in RA patients. METHODS: In this case-control study, the fatigue of 160 RA patients and 60 healthy controls was evaluated by the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ) and the Chinese version of the Brief Fatigue Inventory (BFI-C). The 28-joint disease activity score using erythrocyte sedimentation rate of RA patients was assessed. RESULTS: The BRAF-MDQ and BFI-C scores were elevated in RA patients versus healthy controls (all p < .001). Interestingly, BRAF-MDQ global fatigue score positively correlated with BFI-C global fatigue score in both RA patients (r = .669, p < .001) and healthy controls (r = .527, p < .001); meanwhile, Kendall's tau-b test showed a high consistency between BRAF-MDQ and BFI-C global fatigue scores in RA patients (W = 0.759, p < .001) and healthy controls (W = 0.933, p < .001). Notably, higher education level (В = -4.547; 95% confidence interval: -7.065, -2.029; p < .001) and swollen joint count (В = 1.965; 95% confidence interval: 1.375, 2.554; p < .001) independently related to BRAF-MDQ global fatigue score; higher education level (В = -0.613; 95% confidence interval: -0.956, -0.269; p = .001) and clinical disease activity index (В = 0.053; 95% confidence interval: 0.005, 0.102; p = .032) independently linked with BFI-C global fatigue score. CONCLUSION: Fatigue commonly occurs in RA patients, which independently relates to education level and disease activity. Furthermore, BRAF-MDQ and BFI-C scales exhibit a high consistency in assessing fatigue.