Nationwide Population-based Case-control Study Research Articles

Risk of acute myocardial infarction associated with anti-rheumatic agents in patients with rheumatoid arthritis: a nationwide population-based case-control study

Risk of acute myocardial infarction associated with anti-rheumatic agents in patients with rheumatoid arthritis: a nationwide population-based case-control study

Nocturnal Artificial Light Exposure in Expectant Mothers and Risk of Congenital Glaucoma

Abstract Background While the impact of light pollution on human health is gaining recognition, its role in transmitting the effects of maternal exposure to the fetus remains unclear. This study is to investigate the association between exposure to artificial light at night (ALAN) during pregnancy and risk of congenital glaucoma. Methods All birth cohorts spanning from 2008 to 2011 in urban areas of South Korea, comprising over 90% of the total population, were identified in the Korean National Health Insurance database. Average levels of ALAN at the residential addresses of mothers during pregnancy were estimated using time-varying satellite data for a composite view of persistent night-time illumination at ∼1 km2 scale.The odd ratios (ORs) and 95% confidence intervals (CIs) of the association between residential ALAN and risk of congenital glaucoma - was computed using logistic regression. These calculations were adjusted for socio-demographic factors and area-level risk factors (night-time traffic noise and particulate matter with an aerodynamic diameter ≤ 10 μm). Results A total of 745,458 mother-father-child trios (mean [SD] age of the mothers, 32.4 [3.8] years; 387,275 [52.0%] boy) were included in the study. In fully adjusted models, an IQR (21.8 nW/cm2/sr) increase in ALAN level was associated with an OR of 1.12 (95% CI: 1.05, 1.19) for incident congenital glaucoma. The exposure-response curve demonstrated an upward slope with a threshold at approximately 62 nW/cm2/sr. Conclusions In this nationwide population-based case-control study, higher levels of residential ALAN during pregnancy were associated with increased risk of congenital glaucoma. Future studies with more detailed information on exposure, individual adaptive behaviors and potential mediators are warranted. Key messages • This study indicates an association between elevated levels of ALAN exposure in pregnant women and a heightened risk of congenital glaucoma in their offspring. • These results are consistent with a growing body of evidence underscoring the detrimental effects of ALAN on health, reinforcing its potential role as a risk factor for congenital glaucoma.

Association of antipsychotic formulations with sudden cardiac death in patients with schizophrenia: A nationwide population-based case–control study

The aim of this study was to clarify the association between various antipsychotic formulations—oral-daily antipsychotics (OAPs), long-acting injectable antipsychotics (LAIs), and their combination—and the risk of sudden cardiac death (SCD). We conducted a nationwide population-based case–control study using data from 2011 to 2020 from the National Health Insurance Research Database and multiple-cause-of-death data from Taiwan. The study included patients with a new diagnosis of schizophrenia who were followed for SCD occurrence until 2020. Cases and controls were frequency-matched at a 1:4 ratio by age, sex, and year of new schizophrenia diagnosis. Compared with the use of OAP monotherapy, the use of LAI and OAP combination (OR = 1.91) and LAI monotherapy (OR = 1.45) were associated with an increased risk of SCD. Additionally, cardiovascular comorbidities (adjusted OR = 11.15) were identified as a significant risk factor for SCD. This study revealed the following hierarchy of SCD risk associated with antipsychotic formulations (listed from lowest to highest risk): nonuse of antipsychotics, OAP monotherapy, LAI monotherapy, and their combination. These findings underscore the importance of assessing cardiovascular disease history before LAIs are prescribed to patients with schizophrenia and indicate that physicians should avoid prescribing combined antipsychotics when using LAIs.

Appendicitis links to the afterward subsequent psoriatic disease occurrence in Taiwan national health insurance research database: A population-based cohort study: Appendicitis links to psoriatic diseases.

To investigate the psoriatic disease risk among patients with previous appendicitis. This study was a nationwide population-based case-control study about the association between the psoriatic disease risk among patients with a history of appendicitis in Taiwan. The study population consisted of newly diagnosed psoriatic disease with at least two outpatient visits, and the control group included those patients without psoriatic disease at the same index date. Patients with a previous diagnosis of appendicitis or who underwent appendectomy surgery prior to their psoriatic disease diagnosis were recorded. The odds ratio of psoriatic disease diagnosis in the two groups with and without a history of appendicitis were analyzed and compared. A total of 48 894 individuals diagnosed with psoriatic disease were matched with 292 656 controls by age and gender. Notably, the proportion of patients with a history of appendicitis or primary appendectomy was significantly elevated among those with psoriatic disease compared with the control cohort (both p < .05). On average, the occurrence of appendicitis preceded the index date by 3.3 ± 2.3 years. Multivariate analysis revealed a heightened incidence rate of psoriatic disease in patients previously diagnosed with appendicitis, periodontal disease, Charlson comorbidity index score (CCIS) ≧1, and ill-defined intestinal infections. This association persisted after adjusting for confounding factors, such as periodontal disease, CCIS, Salmonella, and ill-defined intestinal infections. The odds ratios for psoriatic disease in individuals with a history of appendicitis, periodontal disease, CCIS ≧1, and ill-defined intestinal infections were 1.16, 1.008, 1.69, and 1.23, respectively, with corresponding 95% confidence intervals of 1.03-1.31, 1.05-1.11, 1.65-1.74, and 1.20-1.26. These findings underscore the independent association between appendicitis and subsequent development of psoriatic disease, even after adjusting for relevant comorbidities and potential confounders. Our research illustrates that appendicitis is associated with an increased likelihood of developing a psoriatic disease, despite several limitations. These limitations encompass variables such as dietary and smoking habits, alongside other potential confounding factors that were not fully considered. Moreover, inherent biases in utilizing national health insurance data, such as the absence of laboratory information, as well as the constraints inherent in a retrospective study design, should be acknowledged.

Interaction between alimentary surgery and risk of dementia: a nationwide population-based case-control study.

Based on current research, it is known that the gastrointestinal tract microbiota and its genome play a crucial role in mental illnesses. Studies indicate a direct correlation between gastrointestinal tract microbiota and the onset of dementia, mediated by metabolic diseases and low-grade inflammation. The association between various gastrointestinal symptoms and neurodegenerative diseases has been recently discussed. However, there is a lack of research regarding the comparative effects of different surgical procedures on neurodegenerative diseases. Therefore, this study primarily focuses on comparing the association between various gastrointestinal surgeries and dementia, aiming to provide guidance for future clinical practice. A nationwide study using the Taiwanese National Health Insurance Research Database included 26 059 patients diagnosed with dementia or Alzheimer's disease and 104 236 controls without diseases. Primary exposures were defined as alimentary surgeries, encompassing cholecystectomy, gastrectomy, bowel resection, and appendectomy. Conditional logistic regression was used to examine the odds ratio and 95% confidence interval for prior alimentary surgery between cases and controls. The results showed that individuals with dementia had a higher rate of gastrectomy. Additionally, individuals with dementia seemed to exhibit a reduced rate of cholecystectomy and appendectomy. Regarding Alzheimer's disease, all four alimentary surgeries showed comparable trends to those observed with dementia. No significant interaction was observed between alimentary surgery and dementia among the four types of surgery evaluated. Our study demonstrates that gastrectomy is associated with an elevated risk of dementia. We aim to uncover more direct evidence in future experiments.

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.

P098 Association between air pollution and incidence of psoriasis: a nationwide population-based case–control study

P098 Association between air pollution and incidence of psoriasis: a nationwide population-based case–control study

Heightened Prevalence of Common Hospital-Treated Infections Preceding Dementia Diagnosis with Accelerated Dementia Onset after Influenza

BackgroundSince the beginning of Alzheimer’s disease research, the hypothesis that infections are to some extent associated with neurodegenerative processes has been tested repeatedly. Epidemiological studies on the associations between infections and dementia have reported conflicting results.ObjectivesThis study analyses common hospital-treated infections (herpes, influenza, intestinal infections, pneumonia, sepsis, urinary tract infections) and their association with subsequent dementia and time until dementia onset.Design, Setting, and ParticipantsFor this nationwide population-based case-control study, the dataset of the Austrian National Health Insurance Association was used, including dementia patients (dementia cohort) and age- and gender-matched non-demented individuals (control cohort). Only subjects with data availability of at least 10 years prior to the index date (date of dementia diagnosis or date of censoring) were included.MeasurementsThe incidence of six common infections in older adults (herpes, influenza, intestinal infections, pneumonia, sepsis, and urinary tract infections) was analyzed over a period of 10 years before the censoring date.ResultsThe study population consists of 58208 subjects (29104 per study cohort), mean age: 81 years, 54% females. Patients of the dementia cohort had suffered from infections significantly more often than patients of the control cohort (6002, 20.6% vs. 4826, 16.6%; p < 0.001). Influenza, urinary tract infections, intestinal infections, and sepsis showed independent positive associations with subsequent dementia diagnosis, irrespective of other comorbidities (odds ratios: 1.26 (95% CI: 1.06–1.49), 1.23 (95% CI: 1.16–1.30), 1.16 (95% CI: 1.07–1.27), 1.17 (95% CI: 1.01–1.37), respectively). Time from infection to dementia diagnosis was shorter after influenza compared to all other infections (median: 3.4 years (95% CI: 3.1–3.7) vs. 6.6 years (95% CI: 6.4–6.8); p < 0.001).ConclusionThis is the first study to assess the association between infections and dementia over such a long minimum reporting period. These results, supported by consistent data from other epidemiological studies, emphasize the critical importance of infection prevention measures, especially for older adults. Further research is crucial to better understand the nature of the relationship between infections and dementia.

Risk of Secondary Malignancies After Multiple Myeloma: A Nationwide Case-Control Cohort Study

IntroductionIn light of improved survival rates among multiple myeloma (MM) survivors, we sought to assess their risk of secondary malignancies compared to the general population. Materials and MethodsThis nationwide population-based case-control cohort study utilized the Korea National Health Insurance Service (KNHIS) database incorporating data from 2009 to 2020. We analyzed a total of 7348 patients diagnosed with MM in the case cohort. We selected a control group of 29,351 individuals from the general population without MM, employing a 1:4 propensity score matching approach. Matching criteria included age, sex, and comorbidities to ensure a balanced and reliable comparison. ResultsThe cumulative incidence of any secondary malignancy was significantly higher in the case cohort than the control cohort (Hazard ratio [HR] 1.576, 95% confidence interval [CI], [1.381-1.798]). Hematologic malignancy risk was notably higher in the case cohort (HR 8.026, 95% CI, [5.402-11.924]), especially therapy-related myeloid neoplasms (t-MN) (HR 12.063, 95% CI, [6.839-21.278]). No significant difference was shown in nonhematologic malignancy incidence. In subgroup analysis, transplant-eligible MM patients had a significantly higher incidence of any secondary malignancy (HR 1.104, 95% CI, [1.003-1.214]) than transplant-ineligible patients. The incidence of secondary malignancy in MM patients in the lenalidomide-available era was not significantly increased compared to the prelenalidomide era. ConclusionWhile hematologic malignancies, particularly t-MN, are significantly elevated in MM patients compared to general population, nonhematologic malignancies do not appear to be significantly elevated.

Exploring predisposing factors of hearing loss in prematurely born children: A nationwide case-control study

BackgroundWe conducted a nationwide population-based case-control study to analyse potential predisposing factors for hearing loss (HL) that present during the fetal, perinatal, and postnatal periods in prematurely born children. DesignThis study enrolled 21,576 children born at < 37 weeks of gestation; 3,596 with HL and 17,980 with normal hearing born between 2002 and 2015, matched for sex, age at diagnosis, and enrollment time. Data were abstracted from the concatenation of three nationwide databases for overall risk factors till the diagnosis of HL. ResultsMaternal HL, maternal diabetes, particularly type 1 diabetes mellitus, and at or before 32 weeks of gestation were the major obstetric risk factors for HL. Prematurely born children who were born via cesarean section and received a combination of antenatal steroids and magnesium sulfate exhibited a significantly reduced risk of developing HL. Ear malformation was a critical predictor for HL. The major postnatal risk factors included seizure and ototoxic drugs use. Premature infants diagnosed with more than 1 diagnosis of bronchopulmonary dysplasia, necrotizing enterocolitis, and intracerebral hemorrhage were at an increased risk of developing HL. Congenital CMV infection and recurrent acute otitis were also independent postnatal factors for HL in prematurely born children. ConclusionsTo reduce the incidence of childhood HL in prematurely born children, aggressive management of premature birth-related consequences and treatable causes and longitudinal audiological follow-up with early detection and adequate intervention are crucial.

Previous cancers in women diagnosed with premature ovarian insufficiency: A nationwide population-based case-control study.

To investigate the occurrence of previous cancer diagnoses in women suffering from premature ovarian insufficiency (POI) and compare it with the general population, shedding light on the association between cancer, cancer treatments, and POI. We conducted a nationwide case-control study based on registry data from various sources, including the Social Insurance Institution, Finnish Population Information System, and Finnish Cancer Registry spanning from 1953 to 2018. Our participants comprised all women in Finland who, between 1988 and 2017, received hormone replacement therapy reimbursement for ovarian insufficiency before the age of 40 years (n = 5221). Controls, matched in terms of age and municipality of residence, were selected from the Finnish Population Information System (n = 20 822). Our main exposure variable was a history of cancer diagnosis preceding the diagnosis of POI. We analyzed odds ratios (OR) to compare the prevalence of previous cancers in women with POI with that in controls, stratifying results based on cancer type, age at cancer diagnosis, and the time interval between cancer diagnosis and POI. We also assessed changes in OR for previous cancer diagnoses over the follow-up period. Out of the women diagnosed with POI, 21.9% had previously been diagnosed with cancer, resulting in an elevated OR of 36.5 (95% confidence interval [CI] 30.9 to 43.3) compared with 0.8% of the controls. The risk of developing POI was most pronounced during the first 2 years following a cancer diagnosis, with an OR of 103 (95% CI 74.1 to 144). Importantly, this risk remained elevated even when the time interval between cancer and POI exceeded 10 years, with an OR of 5.40 (95% CI 3.54 to 8.23). This study reveals that 21.9% of women with POI have a history of cancer, making the prevalence of cancer among these women 27.5 times higher than age-matched controls in the Finnish population. The risk of developing POI is most substantial in the first 2 years following a cancer diagnosis. These findings underscore the role of cancer treatments as an etiological factor for POI and emphasize the importance of recognizing the risk of POI in cancer survivors for early diagnosis and intervention.

Nighttime Outdoor Artificial Light and Risk of Age-Related Macular Degeneration

Light pollution's impact on human health is increasingly recognized, but its link to exudative age-related macular degeneration (EAMD) remains unclear. To investigate the association between exposure to outdoor artificial light at night (OALAN) and the risk of incident EAMD. In this nationwide population-based case-control study, all individuals 50 years or older with newly diagnosed EAMD between January 1, 2010, and December 31, 2011, were identified with reference to the Korean National Health Insurance Service registration program database for rare and intractable diseases. Birth year- and sex-matched controls (with no EAMD diagnosis until 2020) were selected at a 1:30 ratio. Data were acquired from May 1 to December 31, 2021, and analyzed from June 1 to November 30, 2022. Mean levels of OALAN at participants' residential addresses during 2008 and 2009 were estimated using time-varying satellite data for a composite view of persistent nighttime illumination at an approximate scale of 1 km2. The hazard ratios (HRs) and 95% CIs of the association between residential OALAN and risk of incident EAMD were determined based on maximum likelihood estimation after adjusting for sociodemographic characteristics, comorbidities, and area-level risk factors (ie, nighttime traffic noise and particulate matter of aerodynamic diameter ≤10 μm in each participant's administrative district of residence). A total of 126 418 participants were included in the analysis (mean [SD] age, 66.0 [7.9] years; 78 244 men [61.9%]). Of these, 4078 were patients with newly diagnosed EAMD and 122 340 were EAMD-free matched controls. In fully adjusted models, an IQR (55.8 nW/cm2/sr) increase in OALAN level was associated with an HR of 1.67 (95% CI, 1.56-1.78) for incident EAMD. The exposure-response curve demonstrated a nonlinear, concave upward slope becoming more pronounced at higher levels of light exposure (ie, at approximately 110 nW/cm2/sr). In a subgroup analysis, an IQR increase in OALAN was associated with increased risk of incident EAMD in urban areas (HR, 1.46 [95% CI, 1.33-1.61]) but not in rural areas (HR, 1.01 [95% CI, 0.84-1.22]). In this nationwide population-based case-control study, higher levels of residential OALAN were associated with an increased risk of incident EAMD. Future studies with more detailed information on exposure, individual adaptive behaviors, and potential mediators are warranted.

Preadmission morbidity and healthcare utilization among older adults with potentially avoidable hospitalizations: a Danish case–control study

Key summary pointsAimExamine preadmission diagnoses, medication use, and preadmission healthcare utilization among older adults prior to a first potentially avoidable hospitalization.FindingsOur analysis revealed that preadmission morbidity, medication use, and a high and accelerating number of healthcare contacts are associated with potentially avoidable hospitalizations.MessagePreadmission morbidity and a high number of contacts with general practitioners are associated with potentially avoidable hospitalizations, which highlights the need for tailored clinical initiatives for older adults.

Prevalence of pre-existing lung diseases and their association with income level among patients with lung cancer: a nationwide population-based case-control study in South Korea

BackgroundThis study aimed to estimate the prevalence of pre-existing lung diseases in patients with lung cancer compared to people without lung cancer and examine the association between income levels and...

Dental visits and colon-rectum cancer: A nationwide population-based nested case-control study in Taiwan

Background/purposeAlthough oral health and systemic diseases are closely associated, little is known about the utilization of ambulatory dental visits in patients prior to diagnosis of colon-rectum cancer (CRC). In this study, a nested case-control study based on the population-based health claim database was conducted to clarify the relationship between dental visits and CRC in Taiwan. Materials and methodsFrom the Longitudinal Health Insurance Research Database 2010 (LHIRD 2010), we identified 4787 patients who were newly diagnosed with CRC from 2005 to 2013. We also recruited 19,148 control subjects matched in a 1:4 ratio based on sex and age at the index date from LHIRD 2010. Both groups were retrospectively traced back to 1997 to obtain any records of ambulatory dental visits that occurred within 8 years prior to the index date. ICD-9 codes 520–529 for diseases of oral cavity, salivary glands, and jaw were defined as dental visits. ResultsThe mean frequency of dental visits within 8 years prior to index date among patients with CRC were significantly higher than the control group (P = 0.005). Patients with CRC had significantly higher proportions of certain co-morbidities than control group. However, periodontal treatment, caries filling, and tooth extraction were borderline and not significantly related to CRC after adjustment. ConclusionOur results indicate that the utilization of ambulatory dental visits is significantly increased in patients with CRC prior to its diagnosis. Certain co-morbidities may also affect the frequency of dental visits and the occurrence of CRC.

Hospital-diagnosed morbidities and recent surgery as risk factors for developing Guillain-Barré syndrome.

This study was undertaken to determine the association of hospital-diagnosed morbidity and recent surgery with risk of subsequent Guillain-Barré syndrome (GBS) development. We conducted a nationwide population-based case-control study of all patients with first-time hospital-diagnosed GBS in Denmark between 2004 and 2016 and 10 age-, sex-, and index date-matched population controls per case. Hospital-diagnosed morbidities included in the Charlson Comorbidity Index were assessed as GBS risk factors up to 10 years prior to the GBS index date. Incident major surgery was assessed within 5 months prior. In the 13-year study period, there were 1086 incident GBS cases, whom we compared with 10,747 matched controls. Any pre-existing hospital-diagnosed morbidity was observed in 27.5% of GBS cases and 20.0% of matched controls, yielding an overall matched odds ratio (OR) of 1.6 (95% confidence interval [CI] = 1.4-1.9). The strongest associations were found for leukemia, lymphoma, diabetes, liver disease, myocardial infarction, congestive heart failure, and cerebrovascular disease, with 1.6- to 4.6-fold increased risks of subsequent GBS. GBS risk was strongest for morbidities newly diagnosed during the past 5 months (OR = 4.1, 95% CI = 3.0-5.6). Surgical procedures within 5 months prior were observed in 10.6% of cases and 5.1% of controls, resulting in a GBS OR of 2.2 (95% CI = 1.8-2.7). Risk of developing GBS was highest during the first month following surgery (OR = 3.7, 95% CI = 2.6-5.2). In this large nationwide study, individuals with hospital-diagnosed morbidity and recent surgery had a considerably increased risk of GBS.

Maternal, Perinatal, and Postnatal Predisposing Factors of Hearing Loss in Full-Term Children: A Matched Case-Control Study

Introduction: Studies on risk factors for childhood hearing loss (HL) are usually based on questionnaires or small sample sizes. We conducted a nationwide population-based case-control study to comprehensively analyze the maternal, perinatal, and postnatal risk factors for HL in full-term children. Methods: We retrieved data from three nationwide databases related to maternal characteristics, perinatal comorbidities, and postnatal characteristics and adverse events. We used 1:5 propensity score matching to include 12,873 full-term children with HL and 64,365 age-, sex-, and enrolled year-matched controls. Conditional logistic regression was used to evaluate the risk factors for HL. Results: Among the various maternal factors, maternal HL (adjusted odds ratio [aOR]: 8.09, 95% confidence interval [95% CI]: 7.16–9.16) and type 1 diabetes (aOR: 3.79, 95% CI: 1.98–7.24) had the highest odds of childhood hearing impairment. The major perinatal risk factors for childhood hearing impairment included ear malformations (aOR: 58.78, 95% CI: 37.5–92.0) and chromosomal anomalies (aOR: 6.70, 95% CI: 5.25–8.55), and the major postnatal risk factors included meningitis (aOR: 2.08, 95% CI: 1.18–3.67) and seizure (aOR: 3.71, 95% CI: 2.88–4.77). Other factors included acute otitis media, postnatal ototoxic drug use, and congenital infections. Conclusions: Many risk factors for childhood HL identified in our study are preventable, such as congenital infection, meningitis, ototoxic drug use, and some maternal comorbidities. Accordingly, more effort is required to prevent and control the severity of maternal comorbidities during pregnancy, initiate genetic diagnostic evaluation for high-risk children, and aggressive screening for neonatal infections.

Risk of neurodegenerative diseases in patients with sleep disorders: A nationwide population-based case-control study

ObjectiveOur study aimed to explore the associative relationship between neurodegenerative diseases and sleep disorders. PatientsThis 15-year retrospective longitudinal nationwide population-based matched case-control study used data extracted from the National Health Insurance Research Database. We evaluated 25,589 patients diagnosed with neurodegenerative diseases between 2000 and 2015 and a matched control of 102,356 patients without neurodegenerative diseases. ResultsSleep disorders were an independent risk factor for the development of neurodegenerative diseases (adjusted odds ratio (OR): 1.794, 95% confidence interval (CI): 1.235–2.268, P < 0.001), with a positive dose-effect relationship (adjusted OR (95% CI): <1 year: 1.638 (1.093–2.872), P < 0.001; 1–5 years: 1.897 (1.260–3.135), P < 0.001; >5 years: 2.381 (1.467–3.681), P < 0.001. Moreover, patients with sleep disorder and comorbid depression had a significantly higher risk of neurodegenerative disorders (adjusted OR: 5.874). Subgroup analysis showed that insomnia was associated with Alzheimer's disease, Pick's disease and essential tremor (adjusted OR (95% CI): 1.555 (1.069–1.965), 1.934 (1.331–2.445) and 2.089 (1.439–2.648), respectively). Obstructive sleep apnea was associated with Parkinson's disease, essential tremor, and primary dystonia (adjusted OR (95% CI): 1.801 (1.239–2.275), 5.523 (3.802–6.977), and 4.892 (3.365–6.178), respectively). Other specific sleep disorders were associated with Pick's disease, Parkinson's disease, essential tremor, and primary dystonia (adjusted OR (95% CI): 8.901 (6.101–11.010), 1.549 (1.075–1.986), 2.791 (1.924–3.531), and 9.114 (6.283–10.506), respectively). ConclusionSleep disorders are associated with the subsequent development of neurodegenerative disorders. Moreover, sleep disorder patients with comorbid depression have a higher risk of neurodegenerative diseases.

Association Between Estimated Geocoded Residential Maternal Exposure to Lithium in Drinking Water and Risk for Autism Spectrum Disorder in Offspring in Denmark

Lithium is a naturally occurring and trace element that has mood-stabilizing effects. Maternal therapeutic use of lithium has been associated with adverse birth outcomes. In animal models, lithium modulates Wnt/β-catenin signaling that is important for neurodevelopment. It is unknown whether exposure to lithium in drinking water affects brain health in early life. To evaluate whether autism spectrum disorder (ASD) in offspring is associated with maternal exposure to lithium in drinking water during pregnancy. This nationwide population-based case-control study in Denmark identified 8842 children diagnosed with ASD born from 2000 through 2013 and 43 864 control participants matched by birth year and sex from the Danish Medical Birth Registry. These data were analyzed from March 2021 through November 2022. Geocoded maternal residential addresses during pregnancy were linked to lithium level (range, 0.6 to 30.7 μg/L) in drinking water estimated using kriging interpolation based on 151 waterworks measurements of lithium across all regions in Denmark. ASD diagnoses were ascertained using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes recorded in the Danish Psychiatric Central Register. The study team estimated odds ratios (ORs) and 95% CIs for ASD according to estimated geocoded maternal exposure to natural source of lithium in drinking water as a continuous (per IQR) or a categorical (quartile) variable, adjusting for sociodemographic factors and ambient air pollutants levels. The study team also conducted stratified analyses by birth years, child's sex, and urbanicity. A total of 8842 participants with ASD (male, 7009 [79.3%]) and 43 864 control participants (male, 34 749 [79.2%]) were studied. Every IQR increase in estimated geocoded maternal exposure to natural source of lithium in drinking water was associated with higher odds for ASD in offspring (OR, 1.23; 95% CI, 1.17-1.29). Elevated odds among offspring for ASD were estimated starting from the second quartile (7.36 to 12.67 μg/L) of estimated maternal exposure to drinking water with lithium and the OR for the highest quartile (more than 16.78 μg/L) compared with the reference group (less than 7.39 μg/L) was 1.46 (95% CI, 1.35-1.59). The associations were unchanged when adjusting for air pollution exposures and no differences were apparent in stratified analyses. Estimated maternal prenatal exposure to lithium from naturally occurring drinking water sources in Denmark was associated with an increased ASD risk in the offspring. This study suggests that naturally occurring lithium in drinking water may be a novel environmental risk factor for ASD development that requires further scrutiny.

The Mediatory Role of the Boredom and Loneliness Dimensions in the Development of Problematic Internet Use

In recent years, there has been a gradual digitalization of our society, resulting in intensified technology use for daily life activities, including the emergence of problematic Internet use (PIU). Few studies specifically addressed the boredom and loneliness dimensions in mediating the association between depression, anxiety, and stress levels and the onset of PIU. A nationwide population-based cross-sectional case-control study was carried out by recruiting a sample of Italian young people (aged 18-35). Only 1643 participants were selected for the analyses based on the age and the presence versus absence of PIU. Participants were mainly females (68.7%), with a mean age of 21.8 (SD = 1.7). Non-PIU individuals had significantly stable relationships (p = 0.012), siblings (p = 0.044) and lived with their family (p = 0.010), compared to PIU. PIU individuals displayed significantly higher depression, anxiety, and stress, as well as higher loneliness and boredom levels (all p < 0.001), compared to non-PIU. Depressive symptomatology predicted PIU and that their interaction is positively double mediated by boredom and loneliness (ß = 0.3829 (0.0245), 95%CI = 0.3349-0.4309). Our findings suggested that boredom and loneliness dimensions could act as mediators in the association between depressive symptomatology and the likelihood of PIU onset and maintenance.