Population-based Matched Case-control Study Research Articles

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.

Associations of neighborhood greenspace, and active living environments with autism spectrum disorders: A matched case-control study in Ontario, Canada

BackgroundIncreasing evidence links early life residential exposure to natural urban environmental attributes and positive health outcomes in children. However, few studies have focused on their protective effects on the risk of autism spectrum disorder (ASD). The aim of this study was to investigate the associations of neighborhood greenspace, and active living environments during pregnancy with ASD in young children (≤6 years). MethodsWe conducted a population-based matched case-control study of singleton term births in Ontario, Canada for 2012–2016. The ASD and environmental data was generated using the Ontario Autism Spectrum Profile, the Better Outcomes Registry & Network Ontario, and Canadian Urban Environmental Health Research Consortium. We employed conditional logistic regressions to estimate the odds ratio (OR) between ASD and environmental factors characterizing selected greenspace metrics and neighborhoods conducive to active living (i.e., green view index (GVI), normalized difference vegetation index (NDVI), tree canopy, park proximity and active living environments index (ALE)). ResultsWe linked 8643 mother-child pairs, including 1554 cases (18%). NDVI (OR 1.034, 0.944–1.024, per Inter Quartile Range [IQR] = 0.08), GVI (OR 1.025, 95% CI 0.953–1.087, per IQR = 9.45%), tree canopy (OR 0.992, 95% CI 0.903–1.089, per IQR = 6.24%) and the different categories of ALE were not associated with ASD in adjusted models for air pollution. In contrast, living closer to a park was protective (OR 0.888, 0.833–0.948, per 0.06 increase in park proximity index), when adjusted for air pollution. ConclusionsThis study reported mixed findings showing both null and beneficial effects of green spaces and active living environments on ASD. Further investigations are warranted to elucidate the role of exposure to greenspaces and active living environments on the development of ASD.

Postpartum and non-postpartum depression: a population-based matched case-control study comparing polygenic risk scores for severe mental disorders

It remains inconclusive whether postpartum depression (PPD) and depression with onset outside the postpartum period (MDD) are genetically distinct disorders. We aimed to investigate whether polygenic risk scores (PGSs) for major mental disorders differ between PPD cases and MDD cases in a nested case-control study of 50,057 women born from 1981 to 1997 in the iPSYCH2015 sample in Demark. We identified 333 women with first-onset postpartum depression (PPD group), who were matched with 993 women with first-onset depression diagnosed outside of postpartum (MDD group), and 999 female population controls. Data on genetics and depressive disorders were retrieved from neonatal biobanks and the Psychiatric Central Research Register. PGSs were calculated from both individual-level genetic data and meta-analysis summary statistics from the Psychiatric Genomics Consortium. Conditional logistic regression was used to calculate the odds ratio (OR), accounting for the selection-related reproductive behavior. After adjustment for covariates, higher PGSs for severe mental disorders were associated with increased ORs of both PPD and MDD. Compared with MDD cases, MDD PGS and attention-deficit/hyperactivity disorder PGS were marginally but not statistically higher for PPD cases, with the OR of PPD versus MDD being 1.12 (95% CI: 0 .97–1.29) and 1.11 (0.97–1.27) per-standard deviation increase, respectively. The ORs of PPD versus MDD did not statistically differ by PGSs of bipolar disorder, schizophrenia, or autism spectrum disorder. Our findings suggest that relying on PGS data, there was no clear evidence of distinct genetic make-up of women with depression occurring during or outside postpartum, after taking the selection-related reproductive behavior into account.

Use of healthcare services before diagnosis of attention-deficit/hyperactivity disorder: a population-based matched case-control study

ObjectiveTo compare use of healthcare services and reasons for attendance by children and young people (CYP) with attention-deficit/hyperactivity disorder (ADHD) versus non-ADHD controls.DesignPopulation-based matched case-control study.SettingEnglish primary care electronic health...

Association between number of medications and hip fractures in Japanese elderly using conditional logistic LASSO regression

To examine the association between hip fracture and associated factors, including polypharmacy, and develop an optimal predictive model, we conducted a population-based matched case–control study using the health insurance claims data on hip fracture among Japanese patients. We included 34,717 hospitalized Japanese patients aged ≥ 65 years with hip fracture and 34,717 age- and sex- matched controls who were matched 1:1. This study included 69,434 participants. Overall, 16 variable comorbidities and 60 variable concomitant medications were used as explanatory variables. The participants were added to early elderly and late elderly categories for further analysis. The odds ratio of hip fracture increased with the number of medications only in the early elderly. AUC was highest for early elderly (AUC, 0.74, 95% CI 0.72–0.76). Use of anti-Parkinson’s drugs had the largest coefficient and was the most influential variable in many categories. This study confirmed the association between risk factors, including polypharmacy and hip fracture. The risk of hip fracture increased with an increase in medication number taken by the early elderly and showed good predictive accuracy, whereas there was no such association in the late elderly. Therefore, the early elderly in Japan should be an active target population for hip fracture prevention.

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.

Long-Term Results of Pediatric Congenital Pulmonary Malformation: A Population-Based Matched Case-Control Study with a Mean 7-Year Follow-Up.

Symptomatic congenital pulmonary malformations (CPMs) are a group of anomalies involving the lungs. The long-term outcomes of these patients are not well known. The present research aimed to study the pulmonary function, respiratory morbidity, and health-related quality of life (QoL) of patients treated for CPMs. All children (<16 years of age) treated for CPMs in 2002−2012 (in Oulu University Hospital) were invited to the follow-up visit. Altogether, there were 22 patients, out of which 17 (77%) participated. The mean follow-up time was 6.6 (ranged from 3 to 16) years. Pulmonary function tests, diffusing capacity, respiratory morbidity, and QoL were determined as the primary outcomes. Potential residual malformations and lung anatomy were investigated using computer tomography (CT) imaging. The outcomes were compared to the age- and sex-matched healthy controls. The forced expiratory volume at 1 s (FEV1, Z-score) remained lower in operated patients compared to the healthy controls (−1.57 ± SD 1.35 vs. −0.39 ± SD −0.86, p-value 0.005). There were no differences in respiratory morbidity or QoL between the patients and the controls. The surgical approach (lobectomy vs. partial resection) did not affect lung function. A younger age (<1 year of age) at the time of the surgery seemed to result in a higher lung capacity, but the finding was not statistically significant. Patients with CPMs treated with surgery were satisfied with their wellbeing in the long-term. A lower lung function did not have an impact on their wellbeing. However, there was a slight decrease in lung function compared to the healthy controls, and a clinical follow-up of the patients was recommended.

Risk factors for corneal ulcers: a population-based matched case–control study in Nepal

Background/aimsWe aimed to examine risk factors for corneal ulcer in a rural and peri-urban setting in Nepal.MethodsThis population-based matched case–control study was nested in a cluster randomised trial in 24...

Breast Cancer Incidence among Female Workers by Different Occupations and Industries: A Longitudinal Population-Based Matched Case–Control Study in Taiwan

Background: Breast cancer is the leading cause of cancer incidence worldwide and in Taiwan. The relationship between breast cancer and occupational types remains unclear. This study aimed to investigate lifetime breast cancer incidence by different occupational industries among female workers in Taiwan. Methods: A population-based retrospective case–control study was conducted using three nationwide population-based databases. Matched case and control groups were identified with 1-to-4 exact matching among 103,047 female workers with breast cancer diagnosed in 2008–2017 and those without breast cancer. Their lifetime labor enrollment records were tracked using the National Labor Insurance Database, 1950–2017. Conditional logistic regression was used to analyze the association between types of occupational industries and risk of incident breast cancer. Results: Our study found slightly significant breast cancer risk among the following major occupational classifications: manufacturing (OR: 1.027, 95% CI: 1.011–1.043); wholesale and retail trade (OR: 1.068, 95% CI: 1.052–1.084); information and communication (OR: 1.074, 95% CI: 1.043–1.105); financial and insurance activities (OR: 1.109, 95% CI: 1.086–1.133); real estate activities (OR: 1.050, 95% CI: 1.016–1.085); professional, scientific, and technical activities (OR: 1.118, 95% CI: 1.091–1.145); public administration, defense, and social security (OR: 1.054, 95% CI: 1.023–1.087), education (OR: 1.199, 95% CI: 1.168–1.230); and human health and social work activities (OR: 1.125, 95% CI: 1.096–1.156). Conclusions: Greater percentages of industrial occupations (i.e., manufacturing, wholesale and retail, or health professionals) were associated with slightly increased breast cancer risk. Further studies should investigate the possible risk factors among female workers in those industries with slightly higher incidence of breast cancer.

Association of Patient-Reported Outcomes With Subsequent Nonfatal Self-injury After a New Cancer Diagnosis

Nonfatal self-injury (NFSI) is a patient-centered manifestation of severe distress occurring in 3 out of 1000 patients after cancer diagnosis. How to identify patients at risk for NFSI remains unknown. To examine the associations between patient-reported outcome measures and subsequent NFSI in patients with cancer. This population-based matched case-control study included adults with a new cancer diagnosis reporting an Edmonton Symptom Assessment System (ESAS) score within 36 months of diagnosis in Ontario, Canada, 2007 to 2019. Data analysis was performed January 2007 to December 2019. Cases included patients with NFSI, and controls were patients without NFSI. Cases and controls were matched 1:4. Multivariable conditional logistic regression assessed the association between moderate to severe ESAS symptom scores and total ESAS (t-ESAS, range 0-90) score with NFSI in the subsequent 180 days. Of 408 858 patients reporting 1 or more ESAS assessments, 425 patients experienced NFSI and reported an ESAS score in the preceding 180 days. Of those, 406 cases were matched to 1624 control patients without an NFSI. Cases reported a higher proportion of moderate to severe symptoms and higher t-ESAS score than controls prior to the event. After adjustment, moderate to severe anxiety (odds ratio [OR], 1.61; 95% CI, 1.14-2.27), depression (OR, 1.66; 95% CI, 1.20-2.31), and shortness of breath (OR, 1.65; 95% CI, 1.18-2.31) and each 10-point increase in t-ESAS score (OR, 1.51; 95% CI, 1.40-1.63) were independently associated with higher odds of subsequent NFSI. In this case-control study, reporting moderate to severe anxiety, depression, and shortness of breath and an increasing t-ESAS score after cancer diagnosis were associated with higher odds of NFSI in the following 180 days. These data support the prospective use of routine ESAS screening as a means of identifying patients at higher risk for NFSI to improve supportive care.

Interventions for Shiga toxin-producing Escherichia coli gastroenteritis and risk of hemolytic uremic syndrome: A population-based matched case control study.

The role of antibiotics in the treatment of Shiga toxin-producing Escherichia coli (STEC) infection is controversial. To evaluate the association between treatment (antibiotics, antidiarrheal agents, and probiotics) for STEC infection and hemolytic uremic syndrome (HUS) development. We performed a population-based matched case-control study using the data from the National Epidemiological Surveillance of Infectious Diseases (NESID) between January 1, 2017 and December 31, 2018. We identified all patients with STEC infection and HUS as cases and matched patients with STEC infection without HUS as controls, with a case-control a ratio of 1:5. Further medical information was obtained by a standardized questionnaire. Multivariable conditional logistic regression model was used. 7760 patients with STEC infection were registered in the NESID. 182 patients with HUS and 910 matched controls without HUS were selected. 90 patients with HUS (68 children and 22 adults) and 371 patients without HUS (266 children and 105 adults) were included in the main analysis. The matched ORs of any antibiotics and fosfomycin for HUS in children were 0.56 (95% CI 0.32-0.98), 0.58 (0.34-1.01). The matched ORs for HUS were 2.07 (1.07-4.03), 0.86 (0.46-1.61) in all ages treated with antidiarrheal agent and probiotics. Antibiotics, especially fosfomycin, may prevent the development of HUS in children, while use of antidiarrheal agents should be avoided.

Association of ABO blood group with susceptibility to SARS-CoV-2 infection in Rupandehi district of Nepal.

Objectives:Recent studies after the outbreak of coronavirus disease 2019 have shown an association of the ABO blood group to the susceptibility of severe acute respiratory syndrome coronavirus 2 infection. Anti-A and anti-B antibodies, carbohydrate clustering, interleukin-6 levels and host transmembrane protease serine subtype 2 were suggested to cause the variable susceptibility of severe acute respiratory syndrome coronavirus 2 infection to the ABO blood groups. This study aims to find the association of the ABO blood group with severe acute respiratory syndrome coronavirus 2 infection susceptibility in Nepal.Methods:Population-based matched case–control study was conducted from October 2021 to February 2022 in Rupandehi district of Nepal. A total of 1091 reverse transcription-polymerase chain reaction confirmed coronavirus disease 2019 cases and 2182 controls were included in the study by convenient sampling method.Results:A statistically significant association of severe acute respiratory syndrome coronavirus 2 infection was observed for the blood group AB between cases and controls (11.5% vs 8.5%; odds ratio = 1.4, 95% confidence interval = 1.10–1.78). However, there was no association of severe acute respiratory syndrome coronavirus 2 infection for blood group A (26.7% vs 28.23%; odds ratio = 0.93, 95% confidence interval = 0.79–1.09), B (26.9% vs 29.84%; odds ratio = 0.86, 95% confidence interval = 0.73–1.02) and O (34.9% vs 33.41%; odds ratio = 1.07, 95% confidence interval = 0.92–1.25).Conclusion:This study reported slightly more susceptibility to severe acute respiratory syndrome coronavirus 2 infection among individuals with blood group AB.

The impact of birthweight on the development of cerebral palsy: A population-based matched case-control study

BackgroundCerebral palsy (CP) is a common cause of physical impairment in children, especially in newborns who are small for gestational age (SGA). AimsThe aim of our study was to investigate the association between birth weight and the risk of developing CP, controlling for gestational age and plurality. Study designThis retrospective, observational, case-control study was based on Slovenian Registry of Cerebral Palsy (SRCP) and Slovenian National Perinatal Information System (NPIS) data for the period 2002 to 2010. SubjectsFor each pregnancy that resulted in the birth of the newborn(s) who later developed CP (n = 254), three pregnancies with newborns who did not develop CP (n = 762) were selected and matched for gestational age and plurality. Outcome measuresDiagnosis of CP was made at age 5 years or older by a developmental pediatrician trained in child neurology or a child neurologist using standard measures. ResultsRisk of CP increased progressively as birth weight percentiles fell below the 50th centile, with children in the lowest percentiles at greatest risk. Birth weight percentiles traditionally classified as SGA were an independent risk factor for developing CP, with an odds ratio of 2.43 (95% confidence interval 1.57, 3.73). ConclusionsThe results of this study suggest that the risk for developing CP is inversely related to birth weight, even at birth weights that do not meet the standard definitions of SGA. Synopsis - study questionDoes birth weight represent a potential risk factor for the development of cerebral palsy (CP) when controlling for gestational age and plurality? What's already knownNewborns who are small for gestational age (SGA) are at higher risk of developing CP according to published studies. However, different definitions of SGA (birth weight below the 10th, 5th, or 3rd percentile for gestational age) have been used by researchers and clinicians, making it difficult to compare studies. What this study addsThis study suggests that the risk of developing CP is inversely related to birth weight, even at birth weights that do not meet standard definitions of SGA.

Risk of Symptomatic Kidney Stones During and After Pregnancy

There are several well-known anatomical and physiological changes during pregnancy that could contribute to kidney stone formation, but evidence that they increase the risk of kidney stones during pregnancy is lacking. We determined whether there was an increased risk of a first-time symptomatic kidney stone during and after pregnancy. A population-based matched case-control study. 945 female first-time symptomatic kidney stone formers aged 15-45 years and 1,890 age-matched female controls in Olmsted County, MN, from 1984-2012. The index date was the date of onset of a symptomatic kidney stone for both the case and her matched controls. The primary exposure was pregnancy with assessment for variation in risk across different time intervals before, during, and after pregnancy. Medical records were manually reviewed to determine the conception and delivery dates for pregnancies. Medical record-validated first-time symptomatic kidney stone. Conditional and unconditional multivariable logistic regression analysis. Compared with nonpregnant women, the odds of a symptomatic kidney stone forming in women was similar in the first trimester (OR, 0.92; P=0.8), began to increase during the second trimester (OR, 2.00; P=0.007), further increased during the third trimester (OR, 2.69; P=0.001), peaked at 0 to 3 months after delivery (OR, 3.53; P<0.001), and returned to baseline by 1year after delivery. These associations persisted after adjustment for age and race or for diabetes mellitus, hypertension, and obesity. These results did not significantly differ by age, race, time period, or number of prior pregnancies. Having a prior pregnancy (delivery date>1year ago) was also associated with a first-time symptomatic kidney stone (OR, 1.27; P=0.01). Observational study design in a predominantly White population. The exact timing of stone formation cannot be determined. Pregnancy increases the risk of a first-time symptomatic kidney stone. This risk peaks close to delivery and then improves by 1 year after delivery, though a modest risk of a kidney stone still exists beyond 1 year after delivery.

Diabetes Mellitus and Risk of Plasma Cell and Lymphoproliferative Disorders: A Population Based Study Including 94,579 Cases and 368,348 Matched Controls

Diabetes Mellitus and Risk of Plasma Cell and Lymphoproliferative Disorders: A Population Based Study Including 94,579 Cases and 368,348 Matched Controls

Comorbidity and early death in Danish stage I lung cancer patients – an individualised approach

ABSTRACT:Background: Comorbidity is an important prognostic marker and a treatment indicator for lung cancer patients. Register-based studies often describe the burden of comorbidity by the Charlson comorbidity index (CCI) based on hospital discharge data. We assessed the association between somatic and psychiatric comorbidity and death within one year in early lung cancer and, furthermore, the burden of comorbidity according to treatment type.Material and methods: We conducted a population-based matched case-control study of stage I lung cancer identifying all treated patients who died (all-cause) within one year after diagnosis (early death group, cases). On the basis of data from the Danish Lung Cancer Registry these patients were then matched with two controls who survived more than one year (survivors). Through a review of the medical records, we validated inclusion criteria and collected data on somatic and psychiatric comorbidity. We assessed the association between comorbidity and early death with multivariate conditional logistic regression.Results: We included 221 cases and 410 controls. The mean CCI score in the early death group was 2.3 vs. 1.3 in the survivor group (p < .001). Still, 22% vs. 30% had a CCI score of zero (p = .04) with an average number of comorbidities among these patients of 1.63 vs. 1.06 respectively (p = .006). Among women, 23% in the early death group had depression vs. 13% in the survivor group, corresponding to an unadjusted odds ratio (OR) of 2.0 (CI 95% 1.0–3.7). However, in an adjusted analysis (incl. somatic comorbidities) the OR was 1.7 (CI 95% 0.8–3.5). Patients undergoing oncological therapy were older and tended to have more somatic comorbidities than the surgically treated patients.Conclusion: Comorbidity remains a significant prognostic marker even for stage I lung cancer patients with a CCI score of zero. The suggested association between early death and depression among women needs to be studied further.

Retrospective analysis of the association between tooth loss and dementia: a population-based matched case-control study.

To clarify the association between multiple tooth loss and dementia. Case-control study based on the claims data from National Health Insurance Research Database (NHIRD). Patients were divided into two groups: the dementia groups and non-dementia group. For each case patient, one control patient was randomly selected and frequency matched by age (per 5 years) and sex. The case group comprised patients newly diagnosed with dementia, and the index date was the the date of dementia diagnosis, which became the baseline for comorbidity and age calculations. Among the 43,026 individuals, patients with dementia had a significantly higher extraction density at ages 60-69 (p ⟨ 0.0001) and 70-79 (p = 0.04) years compared with control patients. This population-based retrospective study demonstrated an association between tooth loss and dementia. Patients in Taiwan with more tooth extraction experience are likely to have an increased risk of dementia.

Association between constipation and childhood nocturnal enuresis in Taiwan: a population-based matched case-control study

BackgroundThe relationship between constipation and childhood nocturnal enuresis (NE) has been previously reported; however, this relationship remains controversial. The present study aimed to evaluate the association between constipation and childhood NE.MethodsData from the Longitudinal Health Insurance Database 2000 (LHID 2000) of Taiwan National Health Insurance Research Database from 2000 to 2013 were collected. A total of 2286 children were enrolled in this study: a case group of 1143 children aged 5–18 years who were diagnosed with NE (NE group) and an age- and sex-matched control group of 1143 children without NE. Conditional logistic regression and odds ratio (OR) for NE were used to examine the association between constipation and childhood NE.ResultsThe prevalence of NE in the case group (NE group, aged 5–18 years) was 1.03% from 2000 to 2013. The NE group had a higher percentage of constipation in 1 year before the diagnosis of NE. After stratification for sex, both boys and girls with constipation had higher OR for NE. With stratification for age, children aged 5–12 and 7–12 years had a higher OR for NE.ConclusionsConstipation is associated with childhood NE in Taiwan, particularly in children aged 5–7 and 7–12 years.

Exploring prior diseases associated with incident late-onset Alzheimer's disease dementia.

Studies have identified prior conditions associated with late-onset Alzheimer’s disease dementia (LOAD), but all prior diseases have rarely been screened simultaneously in the literature. Our objective in the present study was to identify prior conditions associated with LOAD and construct pathways for them. We conducted a population-based matched case-control study based on data collected in the National Health Insurance Research database of Taiwan and the Catastrophic Illness Certificate database for the years 1997–2013. Prior diseases definitions were based on the first three digits of the codes listed in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Inclusion criteria required that each ICD-code existed for at least 1 year and incurred at least 2 outpatient visits or inpatient diagnosis. The case group comprised 4,600 patients newly diagnosed with LOAD in 2007–2013. The LOAD patients were matched by sex and age to obtain 4,600 controls. Using stepwise multivariate logistic regression analysis, diseases were screened for 1, 2 …, 9 years prior to the first diagnosis of LOAD. Path analysis was used to construct pathways between prior diseases and LOAD. Our results revealed that the following conditions were positively associated with the incidence of LOAD: anxiety (ICD-code 300), functional digestive disorder (ICD code 564), psychopathology-specific symptoms (ICD-code 307), disorders of the vestibular system (ICD-code 386), concussion (ICD-code 850), disorders of the urethra and urinary tract (ICD-code 599), disorders of refraction and accommodation (ICD-code 367), and hearing loss (ICD-code 389). A number of the prior diseases have previously been described in the literature in a manner identical to that in the present study. Our study supports the assertion that mental, hearing, vestibular system, and functional digestive disorders may play an important role in the pathogenesis of LOAD.

Serum Newborn Screening Blood Metabolites Are not Associated With Childhood-onset Inflammatory Bowel Disease: A Population-based Matched Case-control Study.

Originally used for screening of inborn errors of metabolism, routine metabolite profiles of newborns have also been associated with prematurity and some childhood diseases. We sought to determine whether metabolites measured during routine newborn screening could identify infants who develop inflammatory bowel disease (IBD) in childhood. We conducted a population-based matched case-control study using health administrative data from Ontario, Canada. Children born 2006 to 2015 with IBD were identified using a validated algorithm and matched to 5 controls based on birth date, sex, rural/urban household, and mean neighborhood income quintile at birth. Cases and controls were linked deterministically to metabolic profiles from Newborn Screening Ontario. We fit a lasso penalized logistic regression model and used 10-fold cross-validation to obtain internally valid performance measures. Models included metabolites, amino acids, and endocrine markers. Models also included ratios of metabolites, gestational age, birth weight, mode of delivery, age at serum collection, maternal age at delivery, maternal history of IBD, and parity. Three hundred eight cases of IBD, diagnosed at 5.5 ± 2.8 years, were matched to 1540 controls. No individual metabolites were associated with IBD. The c-statistic was 0.50 for the training data. After 10-fold cross-validation the C statistic was 0.50, indicating no significant association between metabolites and IBD diagnosis. Newborn screening serum metabolites could not identify children who will develop IBD in this population-based cohort. Future studies with an expanded panel of metabolites may provide improved prediction of IBD.