National Case-control Study Research Articles

Social health gradient and risk factors among patients hospitalized for COVID-19 and pre-pandemic respiratory infections. A linked national individual case-control study in Belgium.

The literature establishes a clear social gradient in health for transmissible respiratory diseases. However, this gradient's extent remains largely unexplored in the context of COVID-19, and it is uncertain whether the pandemic has exacerbated this gradient. The study aims to compare the socio-economic profiles and comorbidities during the COVID-19 pandemic with a control population affected by viral pneumonia/respiratory disease in 2019. This case-control study analyzed linked data from all patients hospitalized for COVID-19 in 2020 (n = 22,087) and for respiratory diseases in 2019 (n = 7,586). Socio-economic data from the social security database were linked to clinical data from the hospital registry. We analyzed the socio-demographic and clinical factors associated with COVID-19 hospitalization (control group, wave 1, and wave 2) using multinomial regressions and logistic regression models and the length of stay during hospitalization using binomial negative regressions. A social health gradient was observed in both the COVID-19 and control groups, with a significant increase across waves for COVID-19 (p-trend < 0.0001). Men, people over the age of 45, those with comorbidities, high population density, lower income, lower socio-economic status, and people living in Brussels capital were at higher risk of COVID-19 hospitalization and longer length of stay compared to the control group. Except for sub-Saharan Africans, all patients of foreign nationality had a significantly increased risk of hospitalization (p < 0.001), but a shorter length of stay compared to Belgians. The socio-health gradient for COVID-19 followed the same pattern as that observed in pre-pandemic respiratory diseases, intensifying in the second wave and among the most deprived groups. This study emphasizes the importance of collecting social data alongside clinical data for a better understanding of social health inequalities and for tailoring health prevention policies.

Gestational Diabetes Mellitus and Risk Factors in a Multi-Ethnic National Case-Control Study.

Gestational diabetes mellitus (GDM) continues to increase particularly for non-European women. This study aimed to identify and quantify risk factors for women diagnosed with gestational diabetes in New Zealand to identify women at higher risk. A national dataset of 601,166 eligible women who had ≥ 1 birth in New Zealand between January 2001 and December 2010 identified 11,459 women with gestational diabetes of whom 11,447 were randomly matched with 57,235 control women for age and year of delivery. Adjusted odds ratios (95% CI) showed higher odds of gestational diabetes for Asian (3.60, 3.39-3.82), Pacific (2.76, 2.57-2.96) and Māori (1.23, 1.15-1.31) women compared with European/Other women. Women most economically disadvantaged (1.44, 1.34-1.56), not registered with a lead maternity carer (1.16, 1.04-1.30) and those identified as smokers (1.20, 1.11-1.31) were more likely than control women to develop gestational diabetes. In contrast, women residing in rural (0.83, 0.77-0.88) and remote areas (0.68, 0.60-0.77) were less likely to develop gestational diabetes compared with women living in urban areas, and similarly for non-New Zealand resident women (0.78, 0.72-0.85) compared with resident women. Women who were diagnosed with gestational diabetes were more likely to be non-European, economically disadvantaged, residing in urban areas, unregistered with a lead maternity carer and more likely to smoke. In addition to universal screening for pre-existing diabetes, all women at risk of gestational diabetes should be identified and supported to undertake to a 75 g glucose challenge test between 24 and 28 weeks.

Maternal Hybrid Immunity and Risk of Infant COVID-19 Hospitalizations: National Case-Control Study in Israel

(Abstracted from Nat Commun 2024;15:2846) Infants with COVID-19, especially the Omicron variant, are at increased risk of acute respiratory failure and hospitalization. Pfizer and Moderna mRNA vaccines significantly reduce this risk but are not approved for infants under 6 months.

Pelvic inflammatory disease and risk of borderline ovarian tumors: A national population-based case-control study in Sweden.

The resemblance between fallopian tube cells and serous borderline ovarian tumors (BOTs) suggests a potential origin link, with salpingitis proposed as a contributing factor in the pathogenesis of BOT. This study aimed to explore the potential association between pelvic inflammatory disease (PID) and the risk of developing BOT. A national population-based case-control study in Sweden included women with BOT between 1999 and 2020 and 10 matched controls. Data from nationwide registers were analyzed using conditional logistic regression, adjusting for age, residential district, educational level and parity. Among 4782 cases and 45,167 controls, 2.0% of cases and 1.3% of controls had a history of PID. Previous PID was associated with an increased risk of BOT overall (aOR, 1.48; 95% CI, 1.19-1.85). Significant association was observed with serous tumors (aOR, 1.76; 95% CI, 1.36-2.29), while not with mucinous tumors (aOR, 0.95; 95% CI, 0.60-1.49). A dose-response relationship between number of PID episodes and serous BOT risk was noted (Ptrend < .001). This study demonstrates that PID is associated with increased risk of serous BOT, with a dose response relationship. The study highlights the potential serious implications of upper reproductive tract infections and inflammation. This underscores the need for further investigation of biological mechanisms and possible impact of PID on serous BOT development.

Health care service utilization and drug overdose death:A national nested case-control registry study.

More knowledge is needed to identify and reach those at overdose risk with preventive measures. We examined past 12-month health service utilization, identified the most frequently utilized service, explored this utilization in more detail, and examined correlates of overdose death. A population-based nested case-control registry study including all drug overdose deaths (1 January 2010 to 31 December 2018) in Norway through the Cause of Death Registry (n = 2388). The year-, age- and gender-matched controls included through a population registry (n = 21,465). Data cross-linked with population and patient registries. Multivariable conditional logistic regression analyses estimated the likelihood of overdose death. The cases (vs. controls) attended a higher median number of services (3 vs. 1). The General Practitioner (GP) was the most utilized service. The majority (55.7%) of cases had 11-50 encounters, while the majority (60.7%) of the controls had 1-5 encounters. No high school diploma, no employment, urban living, social welfare benefits/disability pension, single-person household, recent incarceration, multiple health service utilizationand frequent GP encounters, as well psychological and certain physical diagnoses were correlates of overdose death among the GP attenders. The cases had utilized more services than the controls and the GP was the most frequently utilized service. In addition to lowsocioeconomic status, psychological and certain physical diagnoses were correlates of overdose death. This is the first national case-control registry study to document the high utilization of multiple primary and secondary health care services before drug overdose death, as well as reasons for attendance and correlates of overdose death.

Dementia Incidence in Survivors of Multiple Myeloma: A National Case-Control Study Conducted in Korea (The CAREMM-2106 Study)

BackgroundDementia, a growing global health issue, affects older adults and specific groups like long-term cancer survivors. The link between cancer survival and dementia is debated. Multiple myeloma (MM), a common blood cancer in older adults, is often linked with cognitive issues. This study investigated dementia incidence in long-term MM survivors using Korean national data. MethodsA retrospective case-control study used data from the Korea National Health Insurance Service (KNHIS), covering about 50 million Koreans. Patients diagnosed with MM between 2009 and 2020 formed the case cohort, while the control cohort included matched individuals without MM using propensity-score matching. Analyzing baseline characteristics, comorbidities, and socioeconomic status, the primary outcome was dementia incidence identified via ICD-10 codes. Statistical methods included Kaplan-Meier plots, cause-specific and Fine–Gray subdistribution hazard models, and a 3-year landmark analysis for immortal time bias. ResultsThe study included 33,864 patients, with 16,932 in each cohort. The overall cumulative dementia incidence was lower in the MM cohort compared to controls. However, in the first 3 years, MM patients had a higher dementia risk (HR: 1.711, 95% CI, 1.562-1.874) than controls. After 3 years, the risk significantly decreased (HR: 0.625, 95% CI, 0.560-0.696). Age-specific analysis showed a consistent pattern, particularly among MM patients aged 70-79, where dementia risk increased post-3 years. ConclusionThis study reveals a lower long-term dementia risk in MM survivors compared to non-MM individuals. Further prospective studies are needed to confirm these findings and explore the underlying mechanisms.

Re-exploration following caesarean birth: a prospective national case-control study using the United Kingdom Obstetric Surveillance System (UKOSS) data collection system.

Re-exploration following caesarean birth and the associated maternal morbidity has not been investigated in the UK. Our aims were to determine the national incidence and identify the associated risk factors. We conducted a prospective observational case-control study across 194 UK consultant-led maternity units in women whose caesarean birth was complicated by a re-exploration. Independent factors for re-exploration were analysed using multivariable multi-level mixed effects logistic regression. Over the study period (1 June 2021 and 31 May 2022) 238,423 caesarean births were recorded across the UK of which 187 women underwent re-exploration, giving an incidence of one re-exploration per 1282 caesarean births (95%CI 1:1099-1:1471). Haemorrhage (124/187, 66.3%) and sepsis (31/187, 16.6%) were the most common findings at re-exploration. Median (IQR [range]) time interval to re-exploration following the caesarean birth was 1 (0-4 [0-28]) day. Mechanical ventilation was required in 34 (18.6%) women, cardiac arrest was reported in 5 (2.7%) and 3 (1.6%) women died. Independent preceding factors associated with a re-exploration included: receipt of blood transfusion (adjusted OR (95%CI) 8.25 (2.66-25.61)); use of a general anaesthetic (adjusted OR (95%CI) 3.33 (1.61-6.88)); pre-eclampsia (adjusted OR (95%CI) 3.27 (1.55-6.91)); black ethnicity (adjusted OR (95%CI) 3.14 (1.39-7.11)); postpartum haemorrhage (adjusted OR (95%CI) 2.82 (1.81-4.37)); use of anticoagulants or antiplatelet drugs pre-caesarean birth (adjusted OR (95%CI) 2.26 (1.35-3.81)); and emergency caesarean birth (adjusted OR (95%CI) 1.89 (1.01-3.57)). Re-exploration following caesarean birth in the UK is uncommon but is associated with significant maternal morbidity and mortality. These study findings will help guide informed consent and encourage appropriate surveillance of high-risk women postpartum.

Association of opium use and tobacco smoking with α-, β-, and γ-human papillomavirus oral infection.

Head and neck squamous cell carcinomas (HNSCCs) are linked to tobacco smoking, opium use, and human papillomavirus (HPV) infection. However, little is known about the association of HPV infection with risk factors of HNSCCs, including opium and tobacco use. This cross-sectional analysis of a national multi-center case-control study in Iran included 498 HNSCC cases and 242 controls. We investigated the association of opium and tobacco use with α- (n = 21), β- (n = 46), and γ-HPV (n = 52) types in saliva samples using type-specific bead-based multiplex genotyping assays (TS-MPG). We found that α-HPV positivity was significantly associated with tobacco smoking (OR = 10.35; 95% CI = 1.15, 93; p = .03), but not with opium use (OR = 1.06; 95% CI = 0.41, 2.76; p = .89). Additionally, tobacco smoking correlated with an elevated risk of β-species 2 HPV infection (OR = 1.28; 95% CI = 1.04, 1.58; p = .020). Conversely, opium use showed a positive association with γ-species 12 HPV infection (OR = 5.67; 95% CI = 1.43, 22.44; p = .013). These findings indicate that tobacco and opium use may influence the risk of HPV infection in different ways depending on the HPV genus and species. Further studies are needed to replicate these findings in other populations.

Antidepressant drugs and risk of developing glioma: a national registry-based case-control study and a meta-analysis.

Whether use of antidepressants is related to the risk of developing lower-grade (WHO grades 2-3) and higher-grade (WHO grade 4) glioma was investigated in this study. A registry-based case-control study was performed with 1283 glioma case patients and 6400 age-, sex-, and geographically matched control participants who were diagnosed in Sweden during 2009-2013. Conditional logistic regression was used to analyze whether selective serotonin reuptake inhibitors (SSRIs) or non-SSRIs were associated with the risk of developing lower- or higher-grade glioma in the study population. Our results show that use of antidepressant medication was not associated with the risk of developing glioma. We also performed a meta-analysis in which the data set from the present study was combined with results from 2 previous epidemiologic studies to answer the same questions. The meta-analysis showed a modest risk reduction of developing glioma in relation to antidepressant treatment (odds ratio = 0.90; 95% CI, 0.83-0.97) when all glioma subgroups and all forms of antidepressant medications were combined. In conclusion, it remains possible that antidepressants may have common monoaminergic mechanism(s) that reduce the risk of developing glioma.

Occupational exposure to organic solvents and the risk of developing testicular germ cell tumors (TESTIS study): Effect of combined exposure assessment on risk estimation.

Etiological factors of testicular germ cell tumors (TGCT) remain largely unknown, but a causal role of occupational exposures to solvents has been suggested. Previous studies analyzing these exposures reported discordant results, potentially related to exposure assessment methods. The aim of this study was to investigate the role of occupational exposure to solvents on the risk of developing TGCT among young men. This study examined occupational exposures to solvents and TGCT risk based on the lifetime work histories of 454 cases and 670 controls, aged 18-45 years, of the French national TESTIS case-control study. Solvent exposure was estimated using: (i) exposure assignment by job-exposure matrix (JEM) and (ii) JEM combined with self-reported exposure data from specific questionnaires (SQ) and expert assessment (EA). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. Both approaches (JEM and JEM+SQ+EA) showed a consistent association between TGCT and trichloroethylene exposure (exposed versus not exposed; JEM=OR 1.80 [95% confidence interval (CI) 1.12-2.90] and JEM+SQ+EA= OR 2.59 (95% CI 1.42-4.72). Both approaches also observed positive associations with ketone esters and fuels & petroleum-based solvents. The results suggest that some organic solvents might be involved in the pathogenesis of TGCT among occupationally exposed men. The combined use of JEM+SQ+EA seemed to limit misclassification by considering individual exposure variability and is, therefore, an appealing approach to assess occupational exposures in epidemiological studies.

Case-control study of environmental toxins and risk of amyotrophic lateral sclerosis involving the national ALS registry

Objective Neurotoxic chemicals are suggested in the etiology of amyotrophic lateral sclerosis (ALS). We examined the association of environmental and occupational risk factors including persistent organochlorine pesticides (OCPs) and ALS risk among cases from the Centers for Disease Control and Prevention National ALS Registry and age, sex, and county-matched controls. Methods Participants completed a risk factor survey and provided a blood sample for OCP measurement. ALS cases were confirmed through the Registry. Conditional logistic regression assessed associations between ALS and risk factors including OCP levels. Results 243 matched case-control pairs (61.7% male, mean [SD] age = 62.9 [10.1]) were included. Fifteen of the 29 OCPs examined had sufficient detectable levels for analysis. Modest correlations of self-reported years of exposure to residential pesticide mixtures and OCP serum levels were found (p<.001). Moreover, occupational exposure to lead including soldering and welding with lead/metal dust and use of lead paint/gasoline were significantly related to ALS risk (OR = 1.77, 95% CI: 1.11-2.83). Avocational gardening was a significant risk factor for ALS (OR = 1.57, 95% CI: 1.04-2.37). ALS risk increased for each 10 ng/g of α-Endosulfan (OR = 1.42, 95% CI: 1.14-1.77) and oxychlordane (OR = 1.24, 95% CI: 1.01-1.53). Heptachlor (detectable vs. nondetectable) was also associated with ALS risk (OR = 3.57, 95% CI: 1.50-8.52). Conclusion This national case-control study revealed both survey and serum levels of OCPs as risk factors for ALS. Despite the United States banning many OCPs in the 1970s and 1980s, their use abroad and long half-lives continue to exert possible neurotoxic health effects.

Use of progestogens and the risk of intracranial meningioma: national case-control study

ABSTRACTObjectiveTo assess the risk of intracranial meningioma associated with the use of selected progestogens.DesignNational case-control study.SettingFrench National Health Data System (ie, Système National des Données de Santé).ParticipantsOf 108 366 women...

Re-exploration after Caesarean delivery: a prospective national case-control study using the United Kingdom Obstetric Surveillance System (UKOSS)

Re-exploration after Caesarean delivery: a prospective national case-control study using the United Kingdom Obstetric Surveillance System (UKOSS)

Clinical and health inequality risk factors for non-COVID-related sepsis during the global COVID-19 pandemic: a national case-control and cohort study

Sepsis, characterised by significant morbidity and mortality, is intricately linked to socioeconomic disparities and pre-admission clinical histories. This study aspires to elucidate the association between non-COVID-19 related sepsis and health inequality risk factors amidst the pandemic in England, with a secondary focus on their association with 30-day sepsis mortality. With the approval of NHS England, we harnessed the OpenSAFELY platform to execute a cohort study and a 1:6 matched case-control study. A sepsis diagnosis was identified from the incident hospital admissions record using ICD-10 codes. This encompassed 248,767 cases with non-COVID-19 sepsis from a cohort of 22.0 million individuals spanning January 1, 2019, to June 31, 2022. Socioeconomic deprivation was gauged using the Index of Multiple Deprivation score, reflecting indicators like income, employment, and education. Hospitalisation-related sepsis diagnoses were categorised as community-acquired or hospital-acquired. Cases were matched to controls who had no recorded diagnosis of sepsis, based on age (stepwise), sex, and calendar month. The eligibility criteria for controls were established primarily on the absence of a recorded sepsis diagnosis. Associations between potential predictors and odds of developing non-COVID-19 sepsis underwent assessment through conditional logistic regression models, with multivariable regression determining odds ratios (ORs) for 30-day mortality. The study included 224,361 (10.2%) cases with non-COVID-19 sepsis and 1,346,166 matched controls. The most socioeconomic deprived quintile was associated with higher odds of developing non-COVID-19 sepsis than the least deprived quintile (crude OR 1.80 [95% CI 1.77-1.83]). Other risk factors (after adjusting comorbidities) such as learning disability (adjusted OR 3.53 [3.35-3.73]), chronic liver disease (adjusted OR 3.08 [2.97-3.19]), chronic kidney disease (stage 4: adjusted OR 2.62 [2.55-2.70], stage 5: adjusted OR 6.23 [5.81-6.69]), cancer, neurological disease, immunosuppressive conditions were also associated with developing non-COVID-19 sepsis. The incidence rate of non-COVID-19 sepsis decreased during the COVID-19 pandemic and rebounded to pre-pandemic levels (April 2021) after national lockdowns had been lifted. The 30-day mortality risk in cases with non-COVID-19 sepsis was higher for the most deprived quintile across all periods. Socioeconomic deprivation, comorbidity and learning disabilities were associated with an increased odds of developing non-COVID-19 related sepsis and 30-day mortality in England. This study highlights the need to improve the prevention of sepsis, including more precise targeting of antimicrobials to higher-risk patients. The UK Health Security Agency, Health Data Research UK, and National Institute for Health Research.

Mpox (monkeypox) risk and mortality associated with HIV infection: a national case–control study in Nigeria

IntroductionRecent outbreaks of mpox are characterised by changes in the natural history of the disease, the demographic and clinical characteristics of the cases, and widening geographical distribution. We investigated the...

Cohort profile: the United Kingdom Childhood Cancer Study (UKCCS) – a UK-wide population-based study examining the health of cancer survivors

PurposeThe United Kingdom Childhood Cancer Study’s (UKCCS’s) matched cohort was established to examine the longer term morbidity and mortality of individuals previously diagnosed with cancer before 15 years of age,...

Postpartum haemorrhage occurring in UK midwifery units: A national population-based case-control study to investigate incidence, risk factors and outcomes.

To estimate the incidence of, and investigate risk factors for, postpartum haemorrhage (PPH) requiring transfer to obstetric care following birth in midwifery units (MU) in the UK; to describe outcomes for women who experience PPH requiring transfer to obstetric care. We conducted a national population-based case-control study in all MUs in the UK using the UK Midwifery Study System (UKMidSS). Between September 2019 and February 2020, 1501 women with PPH requiring transfer to obstetric care following birth in an MU, and 1475 control women were identified. We used multivariable logistic regression, generating adjusted odds ratios (aORs) and 95% confidence intervals (CIs) to investigate risk factors for PPH requiring transfer to obstetric care. The incidence of PPH requiring transfer to obstetric care following birth in an MU was 3.7% (95% CI 3.6%-3.9%). Factors independently associated with PPH requiring transfer to obstetric care were smoking during pregnancy (aOR = 0.73; 95% CI 0.56-0.94), nulliparity (aOR = 1.96; 95% CI 1.66-2.30), previous PPH (aOR = 2.67; 95% CI 1.67-4.25), complications in a previous pregnancy other than PPH (aOR = 2.40; 95% CI 1.25-4.60), gestational age ≥41 weeks (aOR = 1.36; 95% CI 1.10-1.69), instrumental birth (aOR = 2.69; 95% CI 1.53-4.72), third stage of labour ≥60 minutes (aOR = 5.56; 95% CI 3.93-7.88), perineal trauma (aOR = 4.67; 95% CI 3.16-6.90), and birthweight 3500-3999g (aOR = 1.71; 95% CI 1.42-2.07) or ≥4000g (aOR = 2.31; 95% CI 1.78-3.00). One in ten (10.6%) cases received a blood transfusion and one in five (21.0%) were admitted to higher level care. The risk factors identified in this study align with those identified in previous research and with current guidelines for women planning birth in an MU in the UK. Maternal outcomes after PPH were broadly reassuring and indicative of appropriate management. NHS organisations should ensure that robust guidelines are in place to support management of PPH in MUs.

Pelvic inflammatory disease and risk of epithelial ovarian cancer: a national population-based case-control study in Sweden

Epithelial ovarian cancer is an insidious disease, and women are often diagnosed when the disease is beyond curative treatment. Accordingly, identifying modifiable risk factors is of paramount importance. Inflammation predisposes an individual to cancer in various organs, but whether pelvic inflammatory disease is associated with an increased risk of epithelial ovarian cancer has not been fully determined. This study aimed to investigate a possible association between clinically verified pelvic inflammatory disease and the risk of epithelial ovarian cancer. In this national population-based case-control study, all women in Sweden diagnosed with epithelial ovarian cancer between 1999 and 2020 and 10 controls for each were identified, matched for age and residential district. Using several Swedish nationwide registers, data on previous pelvic inflammatory disease and potential confounding factors (age, parity, educational level, and previous gynecologic surgery) were retrieved. Adjusted odds ratios and 95% confidence intervals were estimated using conditional logistic regression. Histotype-specific analyses were performed for the subgroup of women diagnosed with epithelial ovarian cancer between 2015 and 2020. Moreover, hormonal contraceptives and menopausal hormone therapy were adjusted in addition to the aforementioned confounders. This study included 15,072 women with epithelial ovarian cancer and 141,322 controls. Most women (9102 [60.4%]) had serous carcinoma. In a subgroup of cases diagnosed between 2015 and 2020, high-grade serous carcinoma (2319 [60.0%]) was identified. A total of 168 cases (1.1%) and 1270 controls (0.9%) were diagnosed with pelvic inflammatory disease. Previous pelvic inflammatory disease was associated with an increased risk of epithelial ovarian cancer (adjusted odds ratio, 1.39; 95% confidence interval, 1.17-1.66) and serous carcinoma (adjusted odds ratio, 1.46; 95% confidence interval, 1.18-1.80) for the entire study population. For the subgroup of women diagnosed in 2015-2020, pelvic inflammatory disease was associated with high-grade serous carcinoma (adjusted odds ratio, 1.43; 95% confidence interval, 1.01-2.04). The odds ratios of the other histotypes were as follows: endometrioid (adjusted odds ratio, 0.13; 95% confidence interval, 0.02-1.06), mucinous (adjusted odds ratio, 1.55; 95% confidence interval, 0.56-4.29), and clear cell carcinoma (adjusted odds ratio, 2.30; 95% confidence interval, 0.90-5.86). A dose-response relationship was observed between the number of pelvic inflammatory disease episodes and the risk of epithelial ovarian cancer (Ptrend<.001). A history of pelvic inflammatory disease is associated with an increased risk of epithelial ovarian cancer and a dose-response relationship is evident. Histotype-specific analyses show an association with increased risk of serous epithelial ovarian cancer and high-grade serous carcinoma and potentially also with clear cell carcinoma, but there is no significant association with other histotypes. Infection and inflammation of the upper reproductive tract might have serious long-term consequences, including epithelial ovarian cancer.

The Association of Antibiotic Use and the Odds of a New-Onset ICD Code Diagnosis of Age-Related Macular Degeneration: A Large National Case-Control Study.

The widespread use of antibiotics has many well-documented impacts on the human microbiome, which may be associated with the development of various inflammatory diseases. Despite age-related macular degeneration (AMD) featuring an inflammatory pathogenesis, the relationship between antibiotics and AMD has remained unexplored. We conducted the first study to determine the association between antibiotic exposure and a new-onset International Classification of Diseases (ICD) diagnosis of AMD. We performed a case-control analysis of patients aged 55 and older with new-onset AMD between 2008 and 2017 from a nationwide commercial health insurance claims database. Exposure to antibiotics in the two years before the index date was determined for cases and controls matched one-to-one by age, year, region, anemia, hypertension, and a comorbidity index. Conditional multivariable logistic regression, adjusted for AMD risk factors, was performed to calculate odd ratios (OR) and 95% confidence intervals (CI). Among the antibiotic classes, exposure to aminoglycosides (OR = 1.24; 95% CI, 1.22-1.26) and fluoroquinolones (OR = 1.13; 95% CI, 1.12-1.14) was associated with the greatest odds of a new-onset ICD code diagnosis of AMD. Broad-spectrum antibiotics were associated with nearly three times greater odds of a new-onset ICD code diagnosis of AMD (OR = 1.15; 95% CI, 1.13-1.16) compared to narrow-spectrum antibiotics (OR = 1.05; 95% CI, 1.03-1.07). We also identified a frequency- and duration-dependent association, with a greater cumulative number of antibiotic prescriptions or day supply of antibiotics conferring increased odds of a new-onset ICD code diagnosis of AMD. Greater cumulative exposure to antibiotics, particularly fluoroquinolones, aminoglycosides, and those with broader-spectrum coverage, may be associated with the development of AMD, a finding that requires further investigation using prospective studies.

Utilization of healthcare prior to endometriosis diagnosis: a Danish case-control study.

Do women with endometriosis have higher utilization of primary and secondary healthcare prior to diagnosis compared to women without endometriosis? Women with a hospital-based diagnosis of endometriosis had an overall higher utilization of both primary and secondary healthcare in all 10 years prior to diagnosis. Endometriosis is associated with a diagnostic delay, but only a few studies have investigated the potential consequences of this delay with regard to the utilization of healthcare. To the best of our knowledge, no study has investigated it in a period corresponding to the estimated diagnostic delay. This national Danish registry-based case-control study included 129 696 women. Cases were women with a first-time hospital-based diagnosis of endometriosis between 1 January 2000 and 31 December 2017. We identified 21 616 cases using density sampling. Each case was matched on age at the date of diagnosis (index date) to five women without diagnosed endometriosis (n = 108 080). The utilization of healthcare was assessed for the 10 years before the index. Cases had significantly higher use of healthcare in all 10 years preceding the index. The mean number of yearly contacts with the GP was 9.99 for cases and 7.85 for controls, with an adjusted incidence rate ratio of 1.28 (1.27; 1.29). For hospital contacts, the association increased slightly in the first 9 years and was most profound in the last year preceding index when the adjusted incidence rate ratio was 2.26 (95% CI 2.28; 2.31). We were not able to include women with an endometriosis diagnosis from the general practitioner or private gynaecologist. Therefore, our results are only applicable to hospital-based diagnoses of endometriosis. We do not have information on the specific reasons for contacting the healthcare providers and we can therefore only speculate that the higher utilization of healthcare among cases was related to endometriosis. This study is in agreement with the other known studies on the subject. Future studies should include specific reasons for contacting the healthcare system and thereby identify any specific contact patterns for women with endometriosis. With this knowledge, healthcare professionals could be better at relating certain healthcare seeking behaviour to endometriosis earlier and thereby reduce the time from onset of symptoms to diagnosis. This study is supported by grants from the project 'Finding Endometriosis using Machine Learning' (FEMaLe/101017562), which has received funding from The European Union's Horizon 2020 research and innovation program and Helsefonden (21-B-0141). K.Z. report grants from Bayer AG, Roche Inc. and Volition, royalties from Oxford-Bayer scientific collaboration in gynaecological therapies, non-financial collaboration with the World Endometriosis Society and World Endometriosis Research Foundation and is a Wellbeing of Women research advisory committee member. All this is outside the submitted work. The other authors have no conflict of interest to declare. N/A.