Androgen Deprivation Therapy and the Risk of Newly Developed Dry Eye Syndrome in Patients with Prostate Cancer: A Nationwide Nested Case-Control Study in the Republic of Korea.

Background: We aimed to evaluate the association between androgen deprivation therapy (ADT) and newly developed dry eye syndrome (DES) in patients with prostate cancer. Methods: A nested case-control study was conducted. From the nationwide claims database of the Republic of Korea, 125,005 patients were included in the final analysis. Cases were defined as those newly diagnosed with DES during follow-up, and 12,654 patients were identified. The cases were matched with controls in a ratio of 1:4. Odds ratios (ORs) for newly developed DES associated with ADT were estimated using conditional logistic regression. Results: After matching, 7499 cases and 29,996 controls were selected. ADT was associated with a reduced risk of newly developed DES in patients with prostate cancer compared to no ADT (OR = 0.875; 95% confidence interval, 0.825-0.927; p < 0.0001). An accumulated dose of ADT < 1 year was associated with a reduced risk of incidental DES (OR = 0.811; 95% CI, 0.751-0.875; p < 0.0001), and a duration of 1-2 years was also associated with a reduced risk (OR = 0.890; 95% CI, 0.802-0.986; p = 0.026). No association was observed with an ADT duration of ≥2 years. Conclusions: The use of ADT, especially for shorter durations (<2 years), was associated with a reduced risk of newly developed DES in S. Korean patients with prostate cancer.

Hemorrhagic Moyamoya Angiopathy in European Patients.

BACKGROUND: Moyamoya angiopathy (MMA) is an important cause of juvenile stroke but an overall rare disease among European populations compared with East Asian cohorts. Consecutively, hemorrhagic MMA is described well in East Asian cohorts, but knowledge in non-Asian patients is limited. Literature suggests that disease presentation may vary between those cohorts, also including hemorrhage frequencies. Hence, this article aims to analyze hemorrhagic MMA in European patients. METHODS: We screened for patients of European origin with MMA from a single-center consecutive database of a German hospital specialized on MMA. Those who had a record of intracranial hemorrhage were analyzed individually regarding the type of hemorrhage and use of antiplatelet therapy before and after bleeding onset. To identify associated factors of intracranial hemorrhage, an age- and sex-matched control group was identified from the pool of patients without a history of hemorrhage. Both groups had a comparable follow-up time and were compared in terms of disease presentation, therapeutic interventions, and imaging characteristics, using both univariate tests and multivariate logistic regression analysis. RESULTS: From a pool of 332 patients with MMA we identified 288 of European ancestry. From those, 36 had a record of intracranial hemorrhage (12.5%). Thirty-three patients presenting with 37 events were included for further analysis and case-control-comparison. Most events were intracerebral hemorrhage (n=20; 54%) and subarachnoid hemorrhage (n=11; 30%). 78% developed hemorrhage although no antiplatelet therapy was in use (n=29). Seven patients developed intracranial hemorrhage ipsilateral to prior bypass surgery (21%), while 29 of the control patients had a bypass surgery (88%; P=0.0001). There was no significant difference in terms of unilateral or bilateral disease type, history of hypertension, as well as imaging characteristics (high Suzuki stage and the presence of collateral pathways in conventional angiography, as well as ischemic defects and the presence of microbleeds on cerebral magnetic resonance imaging; P>0.05 in multivariate analysis, respectively). CONCLUSIONS: Bypass surgery was negatively associated with the development of intracranial hemorrhage in MMA in European patients. There was no difference in terms of a history of hypertension between groups, indicating that blood pressure is not the major contributor for rupture of fragile collateral vessels. The investigated imaging characteristics were not associated to hemorrhage onset and, therefore, are not suitable as a tool of screening for patients at risk.

The effect of exposure to radiofrequency fields on cancer risk in the general and working population: A systematic review of human observational studies - Part I: Most researched outcomes.

BACKGROUND: The objective of this review was to assess the quality and strength of the evidence provided by human observational studies for a causal association between exposure to radiofrequency electromagnetic fields (RF-EMF) and risk of the most investigated neoplastic diseases. METHODS: Eligibility criteria: We included cohort and case-control studies of neoplasia risks in relation to three types of exposure to RF-EMF: near-field, head-localized, exposure from wireless phone use (SR-A); far-field, whole body, environmental exposure from fixed-site transmitters (SR-B); near/far-field occupational exposures from use of hand-held transceivers or RF-emitting equipment in the workplace (SR-C). While no restrictions on tumour type were applied, in the current paper we focus on incidence-based studies of selected "critical" neoplasms of the central nervous system (brain, meninges, pituitary gland, acoustic nerve) and salivary gland tumours (SR-A); brain tumours and leukaemias (SR-B, SR-C). We focussed on investigations of specific neoplasms in relation to specific exposure sources (i.e. E-O pairs), noting that a single article may address multiple E-O pairs. INFORMATION SOURCES: Eligible studies were identified by literature searches through Medline, Embase, and EMF-Portal. Risk-of-bias (RoB) assessment: We used a tailored version of the Office of Health Assessment and Translation (OHAT) RoB tool to evaluate each study's internal validity. At the summary RoB step, studies were classified into three tiers according to their overall potential for bias (low, moderate and high). DATA SYNTHESIS: We synthesized the study results using random effects restricted maximum likelihood (REML) models (overall and subgroup meta-analyses of dichotomous and categorical exposure variables), and weighted mixed effects models (dose-response meta-analyses of lifetime exposure intensity). Evidence assessment: Confidence in evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS: We included 63 aetiological articles, published between 1994 and 2022, with participants from 22 countries, reporting on 119 different E-O pairs. RF-EMF exposure from mobile phones (ever or regular use vs no or non-regular use) was not associated with an increased risk of glioma [meta-estimate of the relative risk (mRR) = 1.01, 95 % CI = 0.89-1.13), meningioma (mRR = 0.92, 95 % CI = 0.82-1.02), acoustic neuroma (mRR = 1.03, 95 % CI = 0.85-1.24), pituitary tumours (mRR = 0.81, 95 % CI = 0.61-1.06), salivary gland tumours (mRR = 0.91, 95 % CI = 0.78-1.06), or paediatric (children, adolescents and young adults) brain tumours (mRR = 1.06, 95 % CI = 0.74-1.51), with variable degree of across-study heterogeneity (I2 = 0 %-62 %). There was no observable increase in mRRs for the most investigated neoplasms (glioma, meningioma, and acoustic neuroma) with increasing time since start (TSS) use of mobile phones, cumulative call time (CCT), or cumulative number of calls (CNC). Cordless phone use was not significantly associated with risks of glioma [mRR = 1.04, 95 % CI = 0.74-1.46; I2 = 74 %) meningioma, (mRR = 0.91, 95 % CI = 0.70-1.18; I2 = 59 %), or acoustic neuroma (mRR = 1.16; 95 % CI = 0.83-1.61; I2 = 63 %). Exposure from fixed-site transmitters (broadcasting antennas or base stations) was not associated with childhood leukaemia or paediatric brain tumour risks, independently of the level of the modelled RF exposure. Glioma risk was not significantly increased following occupational RF exposure (ever vs never), and no differences were detected between increasing categories of modelled cumulative exposure levels. DISCUSSION: In the sensitivity analyses of glioma, meningioma, and acoustic neuroma risks in relation to mobile phone use (ever use, TSS, CCT, and CNC) the presented results were robust and not affected by changes in study aggregation. In a leave-one-out meta-analyses of glioma risk in relation to mobile phone use we identified one influential study. In subsequent meta-analyses performed after excluding this study, we observed a substantial reduction in the mRR and the heterogeneity between studies, for both the contrast Ever vs Never (regular) use (mRR = 0.96, 95 % CI = 0.87-1.07, I2 = 47 %), and in the analysis by increasing categories of TSS ("<5 years": mRR = 0.97, 95 % CI = 0.83-1.14, I2 = 41 %; "5-9 years ": mRR = 0.96, 95 % CI = 0.83-1.11, I2 = 34 %; "10+ years": mRR = 0.97, 95 % CI = 0.87-1.08, I2 = 10 %). There was limited variation across studies in RoB for the priority domains (selection/attrition, exposure and outcome information), with the number of studies evenly classified as at low and moderate risk of bias (49 % tier-1 and 51 % tier-2), and no studies classified as at high risk of bias (tier-3). The impact of the biases on the study results (amount and direction) proved difficult to predict, and the RoB tool was inherently unable to account for the effect of competing biases. However, the sensitivity meta-analyses stratified on bias-tier, showed that the heterogeneity observed in our main meta-analyses across studies of glioma and acoustic neuroma in the upper TSS stratum (I2 = 77 % and 76 %), was explained by the summary RoB-tier. In the tier-1 study subgroup, the mRRs (95 % CI; I2) in long-term (10+ years) users were 0.95 (0.85-1.05; 5.5 %) for glioma, and 1.00 (0.78-1.29; 35 %) for acoustic neuroma. The time-trend simulation studies, evaluated as complementary evidence in line with a triangulation approach for external validity, were consistent in showing that the increased risks observed in some case-control studies were incompatible with the actual incidence rates of glioma/brain cancer observed in several countries and over long periods. Three of these simulation studies consistently reported that RR estimates > 1.5 with a 10+ years induction period were definitely implausible, and could be used to set a "credibility benchmark". In the sensitivity meta-analyses of glioma risk in the upper category of TSS excluding five studies reporting implausible effect sizes, we observed strong reductions in both the mRR [mRR of 0.95 (95 % CI = 0.86-1.05)], and the degree of heterogeneity across studies (I2 = 3.6 %). CONCLUSIONS: Consistently with the published protocol, our final conclusions were formulated separately for each exposure-outcome combination, and primarily based on the line of evidence with the highest confidence, taking into account the ranking of RF sources by exposure level as inferred from dosimetric studies, and the external coherence with findings from time-trend simulation studies (limited to glioma in relation to mobile phone use). For near field RF-EMF exposure to the head from mobile phone use, there was moderate certainty evidence that it likely does not increase the risk of glioma, meningioma, acoustic neuroma, pituitary tumours, and salivary gland tumours in adults, or of paediatric brain tumours. For near field RF-EMF exposure to the head from cordless phone use, there was low certainty evidence that it may not increase the risk of glioma, meningioma or acoustic neuroma. For whole-body far-field RF-EMF exposure from fixed-site transmitters (broadcasting antennas or base stations), there was moderate certainty evidence that it likely does not increase childhood leukaemia risk and low certainty evidence that it may not increase the risk of paediatric brain tumours. There were no studies eligible for inclusion investigating RF-EMF exposure from fixed-site transmitters and critical tumours in adults. For occupational RF-EMF exposure, there was low certainty evidence that it may not increase the risk of brain cancer/glioma, but there were no included studies of leukemias (the second critical outcome in SR-C). The evidence rating regarding paediatric brain tumours in relation to environmental RF exposure from fixed-site transmitters should be interpreted with caution, due to the small number of studies. Similar interpretative cautions apply to the evidence rating of the relation between glioma/brain cancer and occupational RF exposure, due to differences in exposure sources and metrics across the few included studies. OTHER: This project was commissioned and partially funded by the World Health Organization (WHO). Co-financing was provided by the New Zealand Ministry of Health; the Istituto Superiore di Sanità in its capacity as a WHO Collaborating Centre for Radiation and Health; and ARPANSA as a WHO Collaborating Centre for Radiation Protection. REGISTRATION: PROSPERO CRD42021236798. Published protocol: [(Lagorio et al., 2021) DOI https://doi.org/10.1016/j.envint.2021.106828].

Dietary Inflammatory Index and Head and Neck Cancer: A Multicenter Case-Control Study in Iran.

BACKGROUND: The inflammatory potential of diet may affect carcinogenesis. This study aimed to determine the association between dietary inflammatory index (DII) and the risk of head and neck cancer (HNC), as well as the interaction between DII and cigarette smoking in HNC development within the Iranian population. Study Design: This is a case-control study. METHODS: In this multicenter case-control study, participants' dietary intake was assessed using a validated 130-item food frequency questionnaire, from which DII was computed. The study recruited 876 new cases from referral hospitals across 10 provinces and 3409 healthy controls who were frequency-matched based on age, gender, and residential place. Logistic regression was used to obtain odds ratios (ORs) for HNC across tertiles of DII, which were adjusted for confounding variables. RESULTS: A higher pro-inflammatory diet was associated with an increased risk of all HNC (OR T3 vs. T1 [95% CI]: 1.31 [1.06, 1.62]; P-trend=0.013). There was a significant association between lip and oral cavity cancers and DII (OR T3 vs. T1 [95% CI]: 1.56 [1.16, 1.66]; P-trend=0.004). Furthermore, an inflammatory diet was associated with an increased risk of pharynx cancer (OR T3 vs. T1 [95% CI]: 2.08 [1.14, 3.79]; P-trend=0.02). Additionally, no significant association was observed between DII and larynx cancer, while an interaction was found between DII and tobacco use on the risk of HNC (OR T3 vs. T1 [95% CI]: 2.52 [1.78, 3.57]; P-interaction=0.03). CONCLUSION: DII was positively associated with HNC risk. There was a significant association between DII and the risk of lip, oral cavity, and pharynx cancers. Additionally, there was an interaction between tobacco use and DII in determining the risk of HNC.

Predicting risk factors for acute pain after hepatobiliary and pancreatic surgery: an observational case control study.

BACKGROUND: Inadequate postoperative analgesia is associated with increased risks of various postoperative complications, longer hospital stay, decreased quality of life and higher costs. OBJECTIVES: This study aimed to investigate the risk factors for moderate-to-severe postoperative pain within the first 24 hours and 24-48 hours after major hepatobiliary pancreatic surgery. METHODS: Data of patients who underwent surgery at the Department of Hepatobiliary Surgery in Henan Provincial People's Hospital were collected from January 2018 to August 2020. Univariate and multivariate logistic regression analyses were used to identify the risk factors of postoperative pain. RESULTS: In total, 2180 patients were included in the final analysis. 183 patients (8.4%) suffered moderate-to-severe pain within 24 hours after operation. The independent risk factors associated with moderate-to-severe pain 24 hours after procedures were younger age (OR, 0.97; 95% CI 0.95 to 0.98, p<0.001), lower body mass index (BMI) (OR, 0.94; 95% CI 0.89 to 0.98, p=0.018), open surgery (OR, 0.34; 95% CI 0.22 to 0.52, p<0.001), and postoperative analgesia protocol with sufentanil (OR, 4.38; 95% CI 3.2 to 5.99, p<0.001). Postoperative hospital stay was longer in patients with inadequate analgesia (p<0.05). CONCLUSION: Age, BMI, laparoscopic surgery, and different analgesic drugs were significant predictors of postoperative pain after major hepatobiliary and pancreatic surgery. TRIAL REGISTRATION: ChiCTR2100049726.

Incidence and Risk Factors of Surgical Site Infection in Abdominal Surgeries: A Scoping Review of Cohort and Case-Control Studies.

Background: Abdominal surgery is considered a high-risk procedure for the development of surgical site infection (SSI). Few studies have evaluated the relative importance of surgical site infection risk factors in terms of consistency in abdominal surgery. Therefore, this comprehensive review article mapped and summarized the evidence aimed to determine the relative importance of the risk factors and incidence of SSIs in abdominal surgery. Methods: A literature review was conducted using electronic databases and search engines such as Scopus, PubMed, and Web of Science up to March 16, 2023. There was no language restriction for the papers to be included in the study. The relative consistency of the risk factors was measured and evaluated using the methodology of the Joanna Briggs Institute. Original peer-reviewed cohort and case-control studies were included if all types of SSIs were included. Meta-analysis was performed to determine the pooled estimates of SSI incidences. Results: Of 14,237 identified records, 107 articles were included in the review. The pooled incidence of SSI was 10.6% (95% CI: 9.02-12.55%, χ2=12986.44, P<0.001). Operative time and higher wound class were both significant consistent risk factors for SSI incidence. Patients' educational status, malnutrition, functional status, and history of neurological/psychiatric disorders were all candidates for consistent risk factors, with insufficient evidence. Conclusion: The findings of the present study indicated that SSI in abdominal surgery was a multifactorial phenomenon with a considerable risk and had different risk factors with various relative importance. Determining the relative importance of the risk factors for the prevention and control of SSI is strongly recommended.This manuscript has been released as a preprint at the research square: (https://doi.org/10.21203/rs.3.rs-3219597/v1).

The association between healthy diet indicator and phytochemical index with prostate cancer odds ratio: a case-control study.

BACKGROUND AND OBJECTIVE: Healthy diets and diets rich in phytochemicals can have health-promoting benefits in prostate cancer. Therefore, this study aimed to explore the possible association between Healthy Diet Indicator (HDI) and Phytochemical Index (PI) with prostate cancer odds ratio. METHODS: This is a case-control study conducted in Shiraz, Iran, involving 62 newly diagnosed prostate cancer cases and 63 hospital-based controls. The study collected demographic and anthropometric data, as well as dietary intake information via a semi-quantitative food frequency questionnaire. Logistic regression models were employed to evaluate the association between HDI and PI with prostate cancer. RESULTS: The study included 120 participants and found that individuals with higher HDI and PI scores had a lower odds ratio of prostate cancer (HDI: odds ratio (OR): 0.322 - confidence interval (CI) 95%: 0.14-0.700 - PI: OR: 0.426 - CI 95%: 0.204-0.888). After adjusting for potential confounders, a lower odds ratio of prostate cancer was observed specifically among those with higher HDI scores (OR: 0.376 - CI 95%: 0.163-0.868). CONCLUSION: The findings of the present study suggest that adopting healthier dietary habits rich in dietary phytochemicals could be effective in preventing and halting the progression of prostate cancer.

Random forests for the analysis of matched case-control studies.

BACKGROUND: Conditional logistic regression trees have been proposed as a flexible alternative to the standard method of conditional logistic regression for the analysis of matched case-control studies. While they allow to avoid the strict assumption of linearity and automatically incorporate interactions, conditional logistic regression trees may suffer from a relatively high variability. Further machine learning methods for the analysis of matched case-control studies are missing because conventional machine learning methods cannot handle the matched structure of the data. RESULTS: A random forest method for the analysis of matched case-control studies based on conditional logistic regression trees is proposed, which overcomes the issue of high variability. It provides an accurate estimation of exposure effects while being more flexible in the functional form of covariate effects. The efficacy of the method is illustrated in a simulation study and within an application to real-world data from a matched case-control study on the effect of regular participation in cervical cancer screening on the development of cervical cancer. CONCLUSIONS: The proposed random forest method is a promising add-on to the toolbox for the analysis of matched case-control studies and addresses the need for machine-learning methods in this field. It provides a more flexible approach compared to the standard method of conditional logistic regression, but also compared to conditional logistic regression trees. It allows for non-linearity and the automatic inclusion of interaction effects and is suitable both for exploratory and explanatory analyses.

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.

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).

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.

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.

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.

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).

Catheter-related thrombosis in a neonatal intensive care unit: a case-control study / Trombose relacionada a cateter em unidade de terapia intensiva neonatal: um estudo de caso-controle

INTRODUCTION: Catheter-related thrombosis (CRT) accounts for most thrombotic events in the neonate. OBJECTIVE: Investigate CRT frequency, association with days of catheter use until diagnosis, and number of catheters used, in a single-center Neonatal Intensive Care Unit. METHODS: A case-control study that included 14 cases and 42 controls. Data collection occurred between January 2017 and December 2020 in a public NICU. Crude odds ratios (COR) were calculated. The study complied with ethical standards from national guidelines. RESULTS: Two hundred and ninety-four neonates used central venous catheters, of which 14 (4.7%) were diagnosed with CRT. Catheter in use when diagnosis was made was centrally inserted central catheters in 8 (57.1%). Before diagnosis, the cumulative duration of catheter use was 34.5 days and the median number of catheters used was three. A higher SNAPPE-II (COR 1.03; 95% CI 1.01-1.06; p=0.03), cumulative days of catheter use >30 (COR 19.11; 95% CI 2.28-160.10; p=0.007) and number of catheters used ≥3 (COR 7.66; 95% CI 1.51-38.70; p=0.01) were associated with CRT. CONCLUSION: CRT cases were associated with clinical severity; number of catheters and cumulative days of catheter use. We suggest that screening for thrombosis should be performed in neonates who need a long time of catheter use and more than three catheters. Reducing the duration and number of venous catheters used will help to reduce CRT.

INTRODUÇÃO: A trombose relacionada ao cateter (TRC) é responsável pela maioria dos eventos trombóticos no neonato. OBJETIVO: Investigar a frequência da TRC, a associação com os dias de uso do cateter até o diagnóstico e o número de cateteres utilizados em uma Unidade de Terapia Intensiva Neonatal unicêntrico. MÉTODOS: Estudo caso-controle que incluiu 14 casos e 42 controles. A coleta de dados ocorreu entre janeiro de 2017 e dezembro de 2020 em uma UTIN pública. Foram calculadas razões de chances brutas (COR). O estudo respeitou os padrões éticos das diretrizes nacionais. RESULTADOS: Duzentos e noventa e quatro neonatos utilizaram cateter venoso central, dos quais 14 (4,7%) foram diagnosticados com TRC. O cateter em uso no momento do diagnóstico foi o cateter central inserido centralmente em 8 (57,1%). Antes do diagnóstico, o tempo acumulado de uso do cateter foi de 34,5 dias e a mediana do número de cateteres utilizados foi de três. Um maior número de dias de uso do cateter >30 (COR 19,11; IC 95% 2,28-160,10; p=0,007) e número de cateteres utilizados >3 (COR 7,66; IC 95% 1,51-38,70; p=0,01). CONCLUSÃO: Os casos de TRC foram associados à gravidade clínica; número de cateteres e dias cumulativos de uso do cateter. Sugerimos que o rastreamento de trombose seja realizado em neonatos que necessitem de longo tempo de uso do cateter e mais de três cateteres. Reduzir a duração e o número de cateteres venosos usados ajudará a reduzir a TRC.

Predicted 25-hydroxyvitamin D over the adult lifetime and the risk of ovarian cancer.

The evidence from previous studies of serum 25-hydroxyvitamin D (25(OH)D) and ovarian cancer risk is not conclusive. However, the 25(OH)D levels were generally only measured in late adulthood, which may not capture the etiologically relevant exposure periods. We investigated predicted 25(OH)D over the adult lifetime in relation to ovarian cancer risk in a population-based case-control study conducted from 2011 to 2016 in Montreal, Canada (n = 490 cases and 896 controls). Predicted 25(OH)D was computed using previously validated regression models. Unconditional multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% CIs for average predicted 25(OH)D over the adult lifetime and ovarian cancer risk. In addition, the relative importance of different periods of past 25(OH)D exposure was explored using a weighted cumulative exposure (WCE) model. For each 20-nmol/L increase in average predicted 25(OH)D over the adult lifetime, the aOR (95% CI) was 0.73 (0.55-0.96). In WCE analyses, the inverse association was strongest for exposures 5 to 20 years and 35 to 55 years prior to diagnosis, with aORs (95% CIs) of 0.82 (0.69-0.94) and 0.79 (0.66-1.02), respectively, for each 20-nmol/L increase in predicted 25(OH)D. These results support an inverse association between 25(OH)D levels in adulthood and ovarian cancer risk. This article is part of a Special Collection on Gynecological Cancers.

Identifying non-genetic factors associated with trigger finger.

BACKGROUND: The non-genetic factors predisposing to trigger finger (TF) have mostly been characterised in small studies from individual institutions. Here, we aimed to provide a more complete picture of TF and its associations. METHODOLOGY: This case-control study used cross-sectional data from the UK Biobank population-based cohort to identify and determine the strength of associations of phenotypic variables with TF. We performed multivariable logistic regression of a multitude of phenotypic factors associated with TF. RESULTS: We identified 2250 individuals with medical and surgical diagnostic codes for TF, and 398,495 controls. TF was found to be significantly associated with age (OR 1.04, 95% CI 1.03-1.04, P < 2.23×10-308), female sex (OR 1.22, 95% CI 1.08-1.39, P = 2.35×10-3), body mass index (OR 1.10, 95% CI 1.04-1.16, P = 5.52×10-4), carpal tunnel syndrome (OR 9.59, 95% CI 8.68-10.59, P < 2.23×10-308), Dupuytren's disease (OR 4.89, 95% CI 4.06-5.89, P < 2.23×10-308), diabetes mellitus without complications (OR 1.35, 95% CI 1.15-1.58, P = 2.03×10-4) and with complications (OR 2.46, 95% CI 1.90-3.17, P = 4.98×10-12), HbA1c (OR 1.01, 95% CI 1.01-1.02, P = 8.99×10-9), hypothyroidism (OR 1.24, 95% CI 1.07-1.43, P = 4.75×10-3) and rheumatoid arthritis (OR 1.33, 95% CI 1.06-1.68, P = 0.014). CONCLUSION: Our results provide evidence supporting the well-known risk factors such as diabetes mellitus, carpal tunnel syndrome, age and female sex. Furthermore, we can confirm putative associations such as hypothyroidism, obesity and rheumatoid arthritis, while providing evidence against others such as hypertension and hyperlipidaemia. A novel finding arising from this study is the strong association with Dupuytren's disease. Our study design allowed us to identify these associations as being independent from carpal tunnel syndrome, thereby indicating a shared pathophysiology between this disease and TF.

Do patients with nephrotic syndrome have an increased risk of osteoporosis? A nationwide population-based retrospective cohort study in Taiwan.

OBJECTIVES: To evaluate whether nephrotic syndrome (NS) and further corticosteroid (CS) use increase the risk of osteoporosis in Asian population during the period January 2000-December 2010. DESIGN: Nationwide population-based retrospective cohort study. SETTING: All healthcare facilities in Taiwan. PARTICIPANTS: A total of 28 772 individuals were enrolled. INTERVENTIONS: 26 614 individuals with newly diagnosed NS between 2000 and 2010 were identified and included in out study. 26 614 individuals with no NS diagnosis prior to the index date were age matched as controls. Diagnosis of osteoporosis prior to the diagnosis of NS or the same index date was identified, age, sex and NS-associated comorbidities were adjusted. PRIMARY OUTCOME MEASURE: To identify risk differences in developing osteoporosis among patients with a medical history of NS. RESULTS: After adjusting for covariates, osteoporosis risk was found to be 3.279 times greater in the NS cohort than in the non-NS cohort, when measured over 11 years after NS diagnosis. Stratification revealed that age older than 18 years, congestive heart failure, hyperlipidaemia, chronic kidney disease, liver cirrhosis and NS-related disease including diabetes mellitus, hepatitis B infection, hepatitis C infection, lymphoma and hypothyroidism, increased the risk of osteoporosis in the NS cohort, compared with the non-NS cohort. Additionally, osteoporosis risk was significantly higher in NS patients with CS use (adjusted HR (aHR)=3.397). The risk of osteoporosis in NS patients was positively associated with risk of hip and vertebral fracture (aHR=2.130 and 2.268, respectively). A significant association exists between NS and subsequent risk for osteoporosis. CONCLUSION: NS patients, particularly those treated with CS, should be evaluated for subsequent risk of osteoporosis.

Association between secondhand smoke exposure and serum sex hormone concentrations among US female adults: a cross-sectional analysis using data from the National Health and Nutrition Examination Survey, 2013-2016.

OBJECTIVE: To estimate the association between secondhand smoke (SHS) exposure and serum sex hormone concentrations in female adults (never smokers and former smokers). DESIGN: Cross-sectional analysis. SETTING: US National Health and Nutrition Examination Survey, 2013-2016. OUTCOME MEASURES: Serum sex hormone measures included total testosterone (TT) and oestradiol (E2), sex hormone-binding globulin (SHBG), the ratio of TT and E2 and free androgen index (FAI). Isotope dilution-liquid chromatography tandem mass spectrometry was used to measure serum TT and E2. SHBG was measured using immunoassay. The ratio of TT and E2 and FAI were calculated. SHS exposure was defined as serum cotinine concentration of 0.05-10 ng/mL. PARTICIPANTS: A total of 622 female participants aged ≥20 years were included in the analysis. RESULTS: For never smokers, a doubling of serum cotinine concentration was associated with a 2.85% (95% CI 0.29% to 5.47%) increase in TT concentration and a 6.29% (95% CI 0.68% to 12.23%) increase in E2 in fully adjusted models. The never smokers in the highest quartile (Q4) of serum cotinine level exhibited a 10.30% (95% CI 0.78% to 20.72%) increase in TT concentration and a 27.75% (95% CI 5.17% to 55.17%) increase in E2 compared with those in the lowest quartile (Q1). For former smokers, SHBG was reduced by 4.36% (95% CI -8.47% to -0.07%, p for trend=0.049) when the serum cotinine level was doubled, and the SHBG of those in Q4 was reduced by 17.58% (95% CI -31.33% to -1.07%, p for trend=0.018) compared with those in Q1. CONCLUSION: SHS was associated with serum sex hormone concentrations among female adults. In never smokers, SHS was associated with increased levels of TT and E2. In former smokers, SHS was associated with decreased SHBG levels.