Population-based Case-control Study Research Articles

Social Networks, Social Determinants and Mortality: Western New York Exposures and Breast Cancer (WEB) Study.

There are few studies of social support and other social determinants of health after breast cancer (BC) diagnosis and their associations with mortality; results have been inconclusive. Further, it is not known if observed associations are specific to women with BC diagnosis or if associations would be similar among healthy women. Women with incident, pathologically confirmed invasive BC, stage I-IV (n = 1012) and healthy frequency age-matched controls (n = 2036), answered a social support questionnaire in prospective follow-up of a population-based case-control study, the Western New York Exposures and Breast Cancer (WEB) Study. At interview, all participants were aged 35-79 years and resident of two counties in Western New York State. Mortality status was ascertained from the National Death Index. Participants were queried regarding the number of their close friends, frequency of seeing them, household size, household income, and marital status. Hazard ratios (HR) and 95% confidence intervals (CI) for BC specific mortality (BC women only) and all-cause mortality were estimated. Lower household income was associated with higher all-cause mortality among women diagnosed with BC (HR 2.48, 95% CI, 1.24-4.97) and similarly among the healthy women (HR 2.63, 95% CI, 1.25-5.53). Number and frequency of seeing friends, marital status, and household size were not associated with mortality, either among BC patients or among healthy women. Among both those diagnosed with BC and healthy women, lower income was associated with more than twice the mortality. Marital status, household size, number or frequency of meeting friends were not associated with survival.

Breast Cancer is Increased in Women with Primary Ovarian Insufficiency.

DNA damage/repair gene variants are associated with both primary ovarian insufficiency (POI) and cancer risk. We hypothesized that a subset of women with POI and family members would have increased risk for cancer. Case-control population-based study using records from 1995-2022. Two major Utah academic healthcare systems serving 85% of the state. Women with POI (n=613) were identified using ICD codes and reviewed for accuracy. Relatives were linked using the Utah Population Database. Cancer diagnoses were identified using the Utah Cancer Registry. The relative risk of cancer in women with POI and relatives was estimated by comparison to population rates. Whole genome sequencing was performed on a subset of women. Breast cancer was increased in women with POI (OR [95%CI] 2.20 [1.30, 3.47]; p=0.0023) and there was a nominally significant increase in ovarian cancer. Probands with POI were 36.5±4.3 years and 59.5±12.7 years when diagnosed with POI and cancer, respectively. Causal and candidate gene variants for cancer and POI were identified.Among second-degree relatives of these women, there was an increased risk of breast (1.28 [1.08, 1.52]; p=0.0078) and colon cancer (1.50 [1.14, 1.94]; p=0.0036). Prostate cancer was increased in first- (1.64 [1.18, 2.23]; p=0.0026), second- (1.54 [1.32, 1.79]; p<0.001), and third-degree relatives (1.33 [1.20, 1.48]; p<0.001). Data suggest common genetic risk for POI and reproductive cancers. Tools are needed to predict cancer risk in women with POI and potentially to counsel about risks of hormone replacement therapy.

COVID-19 infection during pregnancy and risk of early and late spontaneous miscarriages: A matched case-control population-based study.

To evaluate the effect of COVID-19 during the first trimester on the rate of first- and second-trimester miscarriages. Secondary aims include the effect on stillbirths and the correlation between symptom severity and pregnancy outcomes. A retrospective matched case-control population-based study extracted data from electronic medical records of a nationwide database of the second largest healthcare organization that provides medical services to over 2 000 000 patients in Israel. Pregnancy outcomes in COVID-19-positive pregnant patients in 2020 were compared with an age- and gestational-week-matched 1:2 case-control cohort of pre-pandemic pregnant patients that received medical care in 2019. Of 68 485 pregnant women treated in 2020, 2333 were COVID-19-positive during pregnancy: 215 during the first trimester, 791 during the second trimester, and 1327 during the third trimester. We compared these data with the control cohort of 4580 pre-pandemic pregnant patients. The rate of spontaneous miscarriage was significantly higher 146/2187 (6.3%) in COVID-19-positive patients versus 214/4580 (4.7%), (P < 0.01, odds ratio 1.34, 95% confidence interval 1.094-1.691). Most miscarriages occurred during the first trimester in both groups, yet the rates were significantly higher in the study group (5.4% vs 3.8%, P < 0.01). There was no association between COVID-19 severity and miscarriage risk. COVID-19 diagnosis during early pregnancy increased the rate of spontaneous miscarriage in our cohort compared with an age- and gestational-week-matched pre-pandemic control group.

Relation between the Dantu blood group variant and bacteraemia in Kenyan children: a population-based case control study.

The Dantu blood group variant protects against P. falciparum infections but its wider consequences have not been previously explored. Here, we investigate the impact of Dantu on susceptibility to bacteraemia. We conducted a case-control study in children presenting with community-acquired bacteraemia to Kilifi County Hospital in Kenya between 1998 and 2010. We used logistic regression to test for associations between the Dantu marker SNP rs186873296 A>G and both all-cause and pathogen-specific bacteraemia under an additive model. We used date of admission as a proxy measure of malaria transmission intensity, given known differences in malaria prevalence over the course of the study. Dantu was associated with protection from all-cause bacteraemia (OR=0.81, p=0.014), the association being greatest in homozygotes (OR=0.30, p=0.013). This protection was shared across the major bacterial pathogens but, notably, was only significant during the era of high malaria-transmission pre-2003 (OR=0.79, p=0.023). Consistent with previous studies showing the indirect impact on bacteraemia risk of other malaria-associated red cell variants, our study also shows that Dantu is protective against bacteraemia via its effect on malaria risk. Dantu does not appear to be under balancing selection through an increased risk of bacterial infections.

Residential exposure to ambient fine particulate matter (PM2.5) and nitrogen dioxide (NO2) and incident breast cancer among young women in Ontario, Canada

BackgroundAir pollution has been classified as a human carcinogen based largely on findings for respiratory cancers. Emerging, but limited, evidence suggests that it increases the risk of breast cancer, particularly among younger women. We characterized associations between residential exposure to ambient fine particulate matter (PM2.5) and nitrogen dioxide (NO2) and breast cancer. Analyses were performed using data collected in the Ontario Environmental Health Study (OEHS). MethodsThe OEHS, a population-based case-control study, identified incident cases of breast cancer in Ontario, Canada among women aged 18–45 between 2013 and 2015. A total of 465 pathologically confirmed primary breast cancer cases were identified from the Ontario Cancer Registry, while 242 population-based controls were recruited using random-digit dialing. Self-reported questionnaires were used to collect risk factor data and residential histories. Land-use regression and remote-sensing estimates of NO2 and PM2.5, respectively, were assigned to the residential addresses at interview, five years earlier, and at menarche. Logistic regression was used to estimate odds ratios (OR) and their 95 % confidence intervals (CI) in relation to an interquartile range (IQR) increase in air pollution, adjusting for possible confounders. ResultsPM2.5 and NO2 were positively correlated with each other (r = 0.57). An IQR increase of PM2.5 (1.9 µg/m3) and NO2 (6.6 ppb) at interview residence were associated with higher odds of breast cancer and the adjusted ORs and 95 % CIs were 1.37 (95 % CI = 0.98–1.91) and 2.33 (95 % CI = 1.53–3.53), respectively. An increased odds of breast cancer was observed with an IQR increase in NO2 at residence five years earlier (OR = 2.16, 95 % CI: 1.41–3.31), while no association was observed with PM2.5 (OR = 0.96, 95 % CI 0.64–1.42). ConclusionsOur findings support the hypothesis that exposure to ambient air pollution, especially those from traffic sources (i.e., NO2), increases the risk of breast cancer in young women.

Adolescent sleep patterns, genetic predisposition, and risk of multiple sclerosis.

Shift work, insufficient sleep, and poor sleep quality at young age have been associated with increased risk of multiple sclerosis (MS). This study aimed to investigate the potential interaction between aspects of inadequate sleep (short sleep, phase shift, and poor sleep quality) during adolescence and HLA-DRB1*15:01 in relation to MS risk. We used a Swedish population-based case-control study (1253 cases and 1766 controls). Subjects with different sleep patterns during adolescence and HLA-DRB1*15:01 status were compared regarding MS risk by calculating odds ratios (OR) with 95% confidence intervals (CI) using logistic regression models. Additive interaction between aspects of inadequate sleep and HLA-DRB1*15:01 status was assessed by calculating the attributable proportion due to interaction (AP) with 95% CI. Short sleep duration (<7 hours/night) during adolescence acted synergistically with HLA-DRB1*15:01, increasing the risk of MS (AP 0.38, 95% CI 0.01-0.75, p=0.04). Similarly, subjective low sleep quality during adolescence interacted with HLA-DRB1*15:01 regarding risk of MS (AP 0.30, 95% CI 0.06-0.56, p=0.03), whereas phase shift did not significantly influence the risk of the disease, irrespective of HLA-DRB1*15:01 status. Our findings underscore the importance of addressing inadequate sleep during adolescence, particularly in the context of the HLA-DRB1*15:01 allele, as it appears to amplify the risk of subsequently developing MS.

Orofacial Clefts and Maternal Risk Factors: A Population-Based Case–Control Study

Orofacial Clefts and Maternal Risk Factors: A Population-Based Case–Control Study

Inflammatory eye disease is a risk factor for future microscopic colitis: A nationwide population-based matched case control study.

Microscopic colitis (MC) is an inflammatory disorder of the colon. To date, the relationship between inflammatory eye diseases and MC is unclear. To assess whether inflammatory eye disease (iridocyclitis and episcleritis) is a risk factor for MC. We conducted a nationwide matched case control study in Sweden leveraging the ESPRESSO-study (a Swedish database containing data on all biopsies from the gastrointestinal tract from 1965 to 2017). In total, we identified 14,338 patients with biopsy-verified MC (diagnosed from 1981 to 2017). Patients with MC were matched (by age, sex, county and year of birth) with 68,753 controls from the general population and the occurrence of preceding inflammatory eye diseases (defined as diagnosis of episcleritis or iridocyclitis) in the two groups was compared. Multivariable adjusted odds ratios (aORs) were calculated using conditional logistic regression conditioned on the matching variables. A majority of patients with MC were women (71.9%) and the median age at MC diagnosis was 63.3years (interquartile range (IQR)=50.7-72.6). Some 225 (1.6%) MC patients had an earlier record of inflammatory eye disease compared with 614 (0.9%) in controls. These figures corresponded to an aOR of 1.77 (95% CI=1.52-2.07) for inflammatory eye diseases in patients with MC. Compared to siblings, the aOR for previous inflammatory eye diseases in MC was 1.52 (95% CI=1.17-1.98) and patients treated with budesonide, as a proxy for clinically significant disease, had a somewhat higher aOR for previous inflammatory eye diseases. Inflammatory eye diseases are more common in patients subsequently being diagnosed with MC. Our findings highlight that these conditions may have shared causes and inflammatory pathways and are of clinical interest to gastroenterologists, ophthalmologists and general practitioners.

Population-based germline breast cancer gene association studies and meta-analysis to inform wider mainstream testing.

BackgroundGermline genetic testing, previously restricted to familial and young-onset breast cancer, is now offered increasingly broadly to ‘population-type’ breast cancer patients in mainstream oncology clinics, with wide variation in the genes included. MethodsWeighted meta-analysis was performed for three population-based case-control studies (BRIDGES, CARRIERS and UK Biobank) comprising in total 101,397 women with breast cancer and 312,944 women without breast cancer, to quantify for 37 putative breast cancer susceptibility genes (BCSGs) the frequency of pathogenic variants (PVs) in unselected, ‘population-type’ breast cancer cases and their association with breast cancer and its subtypes. ResultsMeta-analysed odds ratios (ORs) and frequencies of PVs in population-type breast cancer cases were generated for BRCA1 (OR= 8.73 (95% CI 7.47-10.20), 1 in 101), BRCA2 (OR=5.68 (5.13-6.30), 1 in 68) and PALB2 (OR= 4.30 (95% CI 3.68-5.03), 1 in 187). For both CHEK2 (OR=2.40 (95% CI 2.21-2.62), 1 in 73) and ATM (OR=2.16 (95%CI 1.93-2.41), 1 in 132) subgroup analysis showed stronger association with ER-positive disease. Magnitude of association and frequency of PVs were low for RAD51C (OR=1.53 (95%CI 1.15-2.04), 1 in 913), RAD51D (OR=1.76, (95%CI 1.15-2.41, 1 in 1079) and BARD1 (OR=2.34 (1.85-2.97), 1 in 672); frequencies and associations were moderately higher restricting to triple-negative breast cancersThe PV-frequency in ‘population-type’ breast cancer cases was very low for ‘syndromic’ BCSGs TP53 (1 in 1844), STK11 (1 in 11,525), CDH1 (1 in 2668), PTEN (1 in 3755) and NF1 (1 in 1470), with metrics of association also modest ranging from OR=3.62 (95%CI 1.98-6.61) for TP53 down to OR=1.60 (95%CI 0.48-5.30) for STK11. ConclusionsThese metrics reflecting ‘population-type’ breast cancer will be informative to defining the appropriate gene set as we continue to expand to germline testing out to more unselected population-type breast cancer cases.

Breast cancer immunophenotypes and serum organochlorine pesticides in Mexican women: Mixture exposure approach

Epidemiological studies on associations between breast cancer (BC) and organochlorine pesticides (OCP) are inconclusive. The majority of studies have evaluated the effect of single compounds without considering multiple OCP exposures and immunophenotypes of BC. We aimed to evaluate the association between BC immunophenotypes and serum OCP mixtures, and identify the main contributors within mixtures. We included 767 histopathologically confirmed incident BC cases and 908 controls from a population-based case-control study conducted from 2007 to 2011 in Northern Mexico. We obtained direct information about sociodemographic, lifestyle and reproductive characteristics. We collected data from clinical records about hormonal receptors (HR) and epidermal growth factor receptor 2 (HER2) expressions. Immunophenotypes were determined as HR+/HER2−, HER2+ or HR−/HER2−. We quantified OCP and metabolites by gas chromatography using an electron capture micro detector. We used Weighted Quantile Sum regression to assess the association of BC and exposure to multiple OCP, and their contribution within the mixture. We found a positive adjusted association between BC and an OCP mixture (OR: 3.48, 95%CI: 2.58, 4.69), whose primary contribution arose from the isomers of hexachlorocyclohexane and endosulfan, as well as endosulfan sulfate. We also identified a mixture negatively associated (OR: 0.13, 95%CI: 0.08, 0.20), characterized by p,p'-DDT and chlordane metabolites. All these associations remained regardless BC immunophenotypes. This is the first epidemiological report that identified serum OCP mixtures associated with BC immunophenotypes. Due to OCP ubiquity, biomagnification, and continuous exposure, they constitute a global problem of persistent exposure that might be related to BC risk.

The Healthy Participant Effect: insights and results from a population-based case-control study on breast cancer.

Agreement to participate in case-control studies has become low. Healthy participant bias resulting from differential response proportions in cases and controls can distort results; however, the magnitude of bias is difficult to assess. We investigated the effect in a large population-based case-control study on breast cancer, with a participation rate of 43.4% and 64.1% for controls and cases. We performed a mortality follow-up in 2020 for 3,813 cases and 7,335 controls recruited between 2002-2005. Standardized mortality ratios (SMR) for overall mortality and selected causes of death were estimated. The mean age at recruitment was 63.1 years. The overall mortality for controls was 0.66 times lower (95%CI 0.62-0.69) than for the reference population. For causes of death other than breast cancer, SMRs were similar in cases and controls (0.70 and 0.64). Higher education was associated with lower SMRs in both cases and controls. Options for adjusting the healthy participant bias are limited if the true risk factor distribution in the underlying population is unknown. However, a relevant bias in this particular case-control study is considered unlikely since a similar healthy participant effect was observed for both controls and cases.

Newborn readmissions and virtual primary care delivery: a population-based case-control study

BackgroundEarly post-discharge assessments for newborns are recommended. Virtual care has become more prevalent during the pandemic, providing an opportunity to better understand its impact on the quality of post-discharge newborn care. The objective of this study was to understand whether primary care visit modality (in-person vs. virtual) is associated with early newborn hospital readmissions and emergency department (ED) visits.MethodsWe conducted a population-based, case-control study using linked health administrative databases between September 1, 2020 and March 31, 2022 in Ontario, Canada. We compared the modality of primary care visits among cases (hospital readmission within 14 days of life) and controls (newborns without a readmission), matched on infant sex, gestational age, and maternal parity. We included an alternative definition of cases as a composite of either a newborn hospital readmission or emergency department (ED) visit or in-hospital death within the first 14 days of life. Conditional logistic regression models were used to model odds ratios (ORs), comparing those exposed to a virtual visit versus in-person visit, adjusting for infant birth weight, birth hospitalization length of stay, neighbourhood level material deprivation, rurality and presence of active maternal comorbidities.ResultsAmong 73,324 eligible newborns, 2,220 experienced a hospital readmission within 14 days of life and were matched to 8,880 controls. Jaundice was the primary reason for readmission (75% of readmissions). Compared to newborns who were seen in-person post-discharge, newborns who were seen virtually had higher odds of hospital readmission (adjusted odds ratio [aOR] 1.41 (95% CI 1.09, 1.83); the magnitude of effect was not different using the composite outcome (aOR 1.35, 95% CI 1.05, 1.75).ConclusionsNewborns who receive a virtual post-discharge visit are more likely than those who receive an in-person visit to require hospital readmission.

Predicting Out-of-Hospital Cardiac Arrest in the General Population Using Electronic Health Records.

The majority of out-of-hospital cardiac arrests (OHCAs) occur among individuals in the general population, for whom there is no established strategy to identify risk. In this study, we assess the use of electronic health record (EHR) data to identify OHCA in the general population and define salient factors contributing to OHCA risk. The analytical cohort included 2366 individuals with OHCA and 23 660 age- and sex-matched controls receiving health care at the University of Washington. Comorbidities, electrocardiographic measures, vital signs, and medication prescription were abstracted from the EHR. The primary outcome was OHCA. Secondary outcomes included shockable and nonshockable OHCA. Model performance including area under the receiver operating characteristic curve and positive predictive value were assessed and adjusted for observed rate of OHCA across the health system. There were significant differences in demographic characteristics, vital signs, electrocardiographic measures, comorbidities, and medication distribution between individuals with OHCA and controls. In external validation, discrimination in machine learning models (area under the receiver operating characteristic curve 0.80-0.85) was superior to a baseline model with conventional cardiovascular risk factors (area under the receiver operating characteristic curve 0.66). At a specificity threshold of 99%, correcting for baseline OHCA incidence across the health system, positive predictive value was 2.5% to 3.1% in machine learning models compared with 0.8% for the baseline model. Longer corrected QT interval, substance abuse disorder, fluid and electrolyte disorder, alcohol abuse, and higher heart rate were identified as salient predictors of OHCA risk across all machine learning models. Established cardiovascular risk factors retained predictive importance for shockable OHCA, but demographic characteristics (minority race, single marital status) and noncardiovascular comorbidities (substance abuse disorder) also contributed to risk prediction. For nonshockable OHCA, a range of salient predictors, including comorbidities, habits, vital signs, demographic characteristics, and electrocardiographic measures, were identified. In a population-based case-control study, machine learning models incorporating readily available EHR data showed reasonable discrimination and risk enrichment for OHCA in the general population. Salient factors associated with OCHA risk were myriad across the cardiovascular and noncardiovascular spectrum. Public health and tailored strategies for OHCA prediction and prevention will require incorporation of this complexity.

The Association Between Antidepressant Use and Drug-Induced Liver Injury: A Nationwide, Population-Based Case-Control Study in Taiwan.

The complex risk factors of liver injury have prevented the establishment of causal relationships. This study aimed to explore the effects of antidepressant class, cumulative days of medication exposure, presence of comorbidities, and the use of confounding drugs on the risk of antidepressant-induced liver injury. The population-based case-control study sample included individuals registered on the Taiwan National Health Insurance Database between 2000 and 2018. Hospitalized patients with suspected drug-induced liver injury were considered as cases, while control subjects were matched 1:1 by age, gender, and index date (the first observed diagnosis of liver injury). Multivariable regression models were performed to evaluate the association between antidepressants and liver injury. The findings showed that antidepressant users exhibited a higher risk of liver injury (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.12-1.20), particularly those prescribed non-selective serotonin reuptake inhibitors (NSRIs; aOR 1.05; 95% CI 1.01-1.10), selective serotonin reuptake inhibitors (SSRIs; aOR 1.22; 95% CI 1.16-1.29), serotonin-norepinephrine reuptake inhibitors (SNRIs; aOR 1.18; 95% CI 1.13-1.24), and others (aOR 1.27; 95%CI 1.14-1.42). Moreover, cases exhibited a more significant proportion of antidepressant usage and longer durations of treatment compared with controls. The risk of liver injury was higher in the first 30 days of use across all classes of antidepressants (aOR 1.24; 95% CI 1.18-1.29). SSRIs or SNRIs are commonly used to treat depression and other psychological disorders, and consideration of their potential effects on the liver is essential.

Childhood adversity and mental health admission patterns prior to young person suicide (CHASE): a case-control 36 year linked hospital data study, Scotland UK 1981-2017.

Childhood adversity is associated with increased later mental health problems and suicidal behaviour. Opportunities for earlier healthcare identification and intervention are needed. To determine associations between hospital admissions for childhood adversity and mental health in children who later die by suicide. Population-based longitudinal case-control study. Scottish in-patient general and psychiatric records were summarised for individuals born 1981 or later who died by suicide between 1991 and 2017 (cases), and matched controls (1:10), for childhood adversity and mental health (broadly defined as psychiatric diagnoses and general hospital admissions for self-harm and substance use). Records were extracted for 2477 'cases' and 24 777 'controls'; 2106 cases (85%) and 13 589 controls (55%) had lifespan hospitalisations. Mean age at death was 23.7; 75.9% were male. Maltreatment or violence-related childhood adversity codes were recorded for 7.6% cases aged 10-17 (160/2106) versus 2.7% controls (371/13 589), odds ratio = 2.9 (95% CI, 2.4-3.6); mental health-related admissions were recorded for 21.7% cases (458/2106), versus 4.1% controls (560/13 589), odds ratio = 6.5 (95% CI, 5.7-7.4); 80% of mental health admissions were in general hospitals. Using conditional logistic models, we found a dose-response effect of mental health admissions <18y, with highest adjusted odds ratio (aOR) for three or more mental health admissions: aORmale = 8.17 (95% CI, 5.02-13.29), aORfemale = 15.08 (95% CI, 8.07-28.17). We estimated that each type of childhood adversity multiplied odds of suicide by aORmale = 1.90 (95% CI, 1.64-2.21), aORfemale = 2.65 (95% CI, 1.94-3.62), and each mental health admission by aORmale = 2.06 (95% CI, 1.81-2.34), aORfemale = 1.78 (95% CI, 1.50-2.10). Our lifespan study found that experiencing childhood adversity (primarily maltreatment or violence-related admissions) or mental health admissions increased odds of young person suicide, with highest odds for those experiencing both. Healthcare practitioners should identify and flag potential 'at-risk' adolescents to prevent future suicidal acts, especially those in general hospitals.

Risk projection for time-to-event outcome from population-based case-control studies leveraging summary statistics from the target population.

Risk stratification based on prediction models has become increasingly important in preventing and managing chronic diseases. However, due to cost- and time-limitations, not every population can have resources for collecting enough detailed individual-level information on a large number of people to develop risk prediction models. A more practical approach is to use prediction models developed from existing studies and calibrate them with relevant summary-level information of the target population. Many existing studies were conducted under the population-based case-control design. Gail et al. (J Natl Cancer Inst 81:1879-1886, 1989) proposed to combine the odds ratio estimates obtained from case-control data and the disease incidence rates from the target population to obtain the baseline hazard function, and thereby the pure risk for developing diseases. However, the approach requires the risk factor distribution of cases from the case-control studies be same as the target population, which, if violated, may yield biased risk estimation. In this article, we propose two novel weighted estimating equation approaches to calibrate the baseline risk by leveraging the summary information of (some) risk factors in addition to disease-free probabilities from the targeted population. We establish the consistency and asymptotic normality of the proposed estimators. Extensive simulation studies and an application to colorectal cancer studies demonstrate the proposed estimators perform well for bias reduction in finite samples.

Season, household registry and isolated birth defects: a population-based case-control study in Danyang, China.

A birth population-based study was conducted in Danyang, Jiangsu Province, to evaluate major birth defects in emerging regions in China with similar maternal and neonatal care conditions. We conducted a population-based study in a cohort of infants born in Danyang from 2014 to 2021, including 55 709 perinatal infants. Four categories of isolated birth defects were defined as cases: congenital heart defects (CHDs; n=2138), polydactyly (n=145), cleft lip with or without palate (CL/P; n=76) and accessory auricles (n=93). Infants with congenital malformations were identified by the Chinese Birth Defects Monitoring Network. Compared with autumn, conception in spring (OR=1.31 [1.16-1.48]) and winter (OR=1.39 [1.23-1.58]) was associated with an increased risk of CHD. Increased risk of CHD, CL/P and accessory auricles was significantly associated with non-local registered residence (OR=1.17 [1.07-1.28], OR=2.73 [1.52-4.88] and OR=2.11 [1.20-3.71], respectively). Individuals of Han nationality were less likely to have polydactyly (OR=0.23 [0.05-0.98]). The season of pregnancy was significantly associated with CHDs. Offspring of mothers with non-local registered hometown had greater risks of CHDs, CL/P and accessory auricles.

Tattoos as a risk factor for malignant lymphoma: a population-based case–control study

The popularity of tattoos has increased dramatically over the last few decades. Tattoo ink often contains carcinogenic chemicals, e.g., primary aromatic amines, polycyclic aromatic hydrocarbons, and metals. The tattooing process invokes an immunologic response that causes translocation of tattoo ink from the injection site. Deposition of tattoo pigment in lymph nodes has been confirmed but the long-term health effects remain unexplored. We used Swedish National Authority Registers with full population coverage to investigate the association between tattoo exposure and overall malignant lymphoma as well as lymphoma subtypes. We performed a case-control study where we identified all incident cases of malignant lymphoma diagnosed between 2007 and 2017 in individuals aged 20-60 years in the Swedish National Cancer Register. Three random age- and sex-matched controls per case were sampled from the Total Population Register using incidence density sampling. We assessed exposure through a questionnaire in 2021, and data on potential confounders were retrieved from registers. We used multivariable logistic regression to estimate the incidence rate ratio (IRR) of malignant lymphoma in tattooed individuals. The study population consisted of 11,905 individuals, and the response rate was 54% among cases (n=1398) and 47% among controls (n=4193). The tattoo prevalence was 21% among cases and 18% among controls. Tattooed individuals had a higher adjusted risk of overall lymphoma (IRR=1.21; 95% CI 0.99-1.48). The risk of lymphoma was highest in individuals with less than two years between their first tattoo and the index year (IRR=1.81; 95% CI 1.03-3.20). The risk decreased with intermediate exposure duration (three to ten years) but increased again in individuals who received their first tattoo ≥11 years before the index year (IRR=1.19; 95% CI 0.94-1.50). We found no evidence of increasing risk with a larger area of total tattooed body surface. The risk associated with tattoo exposure seemed to be highest for diffuse large B-cell lymphoma (IRR 1.30; 95% CI 0.99-1.71) and follicular lymphoma (IRR 1.29; 95% CI 0.92-1.82). Our findings suggested that tattoo exposure was associated with an increased risk of malignant lymphoma. More epidemiologic research is urgently needed to establish causality. The Swedish Research Council for Health, Working Life and Welfare.

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

The evidence from previous studies of serum 25-hydroxyvitamin D [25(OH)D] and ovarian cancer risk are not conclusive. However, 25(OH)D was 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 (490 cases, 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 (aOR) and 95% confidence intervals (CI) for average predicted 25(OH)D over the adult life and 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 life, 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 in adulthood and ovarian cancer risk.

Risk factors for the development of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis, following drug administration: a systematic review and meta-analysis.

Risk factors for the development of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis, following drug administration: a systematic review and meta-analysis.