Nationwide Population-based Prospective Cohort Study Research Articles

Prevalence of long COVID complaints in persons with and without COVID-19

We studied the prevalence and patterns of typical long COVID complaints in ~ 2.3 million individuals aged 18–70 years with and without confirmed COVID-19 in a Nation-wide population-based prospective cohort study in Norway. Our main outcome measures were the period prevalence of single-occurring or different combinations of complaints based on medical records: (1) Pulmonary (dyspnea and/or cough), (2) Neurological (concentration problems, memory loss), and/or (3) General complaints (fatigue). In persons testing positive (n = 75 979), 64 (95% confidence interval: 54 to 73) and 122 (111 to 113) more persons per 10 000 persons had pulmonary complaints 5–6 months after the test compared to 10 000 persons testing negative (n = 1 167 582) or untested (n = 1 084 578), respectively. The corresponding difference in prevalence of general complaints (fatigue) was 181 (168 to 195) and 224 (211 to 238) per 10 000, and of neurological complaints 5 (2 to 8) and 9 (6–13) per 10 000. Overlap between complaints was rare. Long COVID complaints were only slightly more prevalent in persons with than without confirmed COVID-19. Still, long COVID may pose a substantial burden to healthcare systems in the future given the lasting high incidence of symptomatic COVID-19 in both vaccinated and unvaccinated individuals.

Clinical features and prognostic factors in adults with viral meningitis.

Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined. This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1-4) 30 days after discharge were examined by modified Poisson regression. In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419/1066 (39%), herpes simplex virus type 2 in 171/1066 (16%), varicella-zoster virus in 162/1066 (15%), miscellaneous viruses in 31/1066 (3%) and remained unidentified in 283/1066 (27%). The median age was 33 years (IQR 27-44), and 576/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131/171 (77%) were females. Immunosuppression [32/162 (20%)] and shingles [90/149 (60%)] were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3-7.1), and the median CSF leucocyte count was 160 cells/µl (IQR 60-358). The outcome was unfavourable in 216/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95-1.88) for enteroviruses, 1.55 (95% CI 1.00-2.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98-2.33) for varicella-zoster virus and 1.37 (95% CI 0.61-3.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03-1.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus. In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.

Validation and reliability of the Dutch version of the EORTC QLQ-BLM30 module for assessing the health-related quality of life of patients with muscle invasive bladder cancer

BackgroundQuality of Life (QoL) of bladder cancer patients has been largely neglected. This is partly due to the lack of well-validated QoL questionnaires. The aim of this study is to examine the structural validity, reliability (i.e., internal consistency and test-retest reliability), construct validity (i.e., divergent validity and known group validity) and responsiveness of the Dutch version of the European Organisation for Research and Treatment of Cancer QoL questionnaire for muscle invasive bladder cancer (EORTC-QLQ-BLM30).MethodsPatients with newly diagnosed muscle invasive bladder cancer (MIBC) participating in the population-based ‘Blaaskankerzorg In Beeld’ (BlaZIB) study who completed the EORTC-QLQ-BLM30 at baseline were included. BlaZIB is a Dutch nationwide population-based prospective cohort study collecting clinical data and QoL data of bladder cancer patients. QoL is assessed with a self-administered questionnaire at four points in time: 6 weeks (baseline), 6 months, 12 months and 24 months after diagnosis. Confirmatory factor analysis and multitrait scaling analysis were used to investigate and adapt the scale structure. Reliability, construct validity and responsiveness of the revised scales were evaluated.ResultsOf the 1542 patients invited to participate, 650 patients (42.2%) completed the QLQ-BLM30 at baseline. The questionnaire’s scale structure was revised into seven scales and eight single items. Internal consistency and test-reliability were adequate for most scales (Cronbach’s α ≥0.70 and intraclass correlation coefficient ≥ 0.70, respectively), with the exception of the revised urostomy problem scale and abdominal bloating and flatulence scale. The questionnaire exhibited little overlap with the EORTC-QLQ-C30: all correlations were < 0.40, except for the correlation between emotional function (QLQ-C30) and future worries (QLQ-BLM30). The questionnaire was able to distinguish between patient subgroups formed on the basis of physical function, but not – as hypothesized– based on stage. Changes in health due to treatment were captured by the questionnaire, indicating that the questionnaire is responsive to change.ConclusionsThis study shows that the adapted scale structure of the EORTC-QLQ-BLM30 generally exhibits good measurement properties in Dutch patients, but needs to be validated in other languages and settings.Trial registrationBlaZIB, NL8106, www.trialregister.nl

Association between Retinal Vein Occlusion and Psoriasis in Korea: A Nationwide Population-based Prospective Cohort Study

Psoriasis is a chronic inflammatory skin disease imparting increased risk of cardiovascular diseases. Until now, few studies have reported an increased incidence of ophthalmological retinal vasculopathy in individuals with psoriasis. This study aimed to investigate the association between psoriasis and retinal vein occlusion in the Korean population. Data collected by the National Health Insurance Service between 2009 and 2015 in Korea were analysed. Participants who underwent national health examinations from 2009 to 2012 were enrolled in this study and were divided into either the psoriasis group (n = 3,088) or the control group (n = 465,205). All occurrences of retinal vein occlusion were observed, and the incidence rate of retinal vein occlusion was compared between the psoriasis and control groups. A Cox proportional hazards regression analysis was used to assess the association between psoriasis and newly developed retinal vein occlusion. During a mean 4.37-year follow-up period, 2,034 patients developed retinal vein occlusion. According to multivariable Cox proportional hazard models, individuals with psoriasis had a significantly higher risk of retinal vein occlusion compared with controls (hazard ratio 1.72, 95% confidence interval 1.18–2.51) after adjustments for covariates. This study found that psoriasis was positively associated with retinal vein occlusion.

Association between Retinal Vein Occlusion and Psoriasis in Korea: A Nationwide Population-based Prospective Cohort Study.

Psoriasis is a chronic inflammatory skin disease imparting increased risk of cardiovascular diseases. Until now, few studies have reported an increased incidence of ophthalmological retinal vasculopathy in individuals with psoriasis. This study aimed to investigate the association between psoriasis and retinal vein occlusion in the Korean population. Data collected by the National Health Insurance Service between 2009 and 2015 in Korea were analysed. Participants who underwent national health examinations from 2009 to 2012 were enrolled in this study and were divided into either the psoriasis group (n = 3,088) or the control group (n = 465,205). All occurrences of retinal vein occlusion were observed, and the incidence rate of retinal vein occlusion was compared between the psoriasis and control groups. A Cox proportional hazards regression analysis was used to assess the association between psoriasis and newly developed retinal vein occlusion. During a mean 4.37-year follow-up period, 2,034 patients developed retinal vein occlusion. According to multivariable Cox proportional hazard models, individuals with psoriasis had a significantly higher risk of retinal vein occlusion compared with controls (hazard ratio 1.72, 95% confidence interval 1.18-2.51) after adjustments for covariates. This study found that psoriasis was positively associated with retinal vein occlusion.

Predictors of pocket hematoma after cardiac implantable electronic device surgery: A nationwide cohort study.

PurposeClinically significant pocket hematoma (CSH) is a common complication to cardiac implantable electronic device (CIED) surgery. We aimed to evaluate predictors of CSH after CIED surgery.MethodsWe performed a nationwide population‐based prospective cohort study with systematic patient chart review of all Danish patients undergoing CIED surgery during a 12‐month period. Multiple logistic regression analysis was used to estimate adjusted odds ratios (aOR) with 95% confidence intervals for association between predictors and CSH.ResultsWe included 5918 consecutive patients, 63% males, mean age 72.6 years. A total of 148 (2.5%) patients experienced CSH, including 10 patients (0.2%) requiring re‐operation with hematoma evacuation. The risk of CSH was significantly increased in patients treated with aspirin (aOR 1.8; 1.2–2.7), aspirin and clopidogrel (aOR 3.9; 2.3–6.5), or heparin (aOR 2.1; 1.1–4.1), and in patients with INR≥2.0 (aOR 2.0; 1.2–3.2). Patients operated by low‐volume operators (aOR 2.7; 1.6–4.6) or undergoing more complex CIED surgery such as cardiac resynchronization therapy (aOR 2.0; 1.1–3.5) or dual‐chamber defibrillator (aOR 2.1; 1.2–3.8) also had significantly increased CSH risk.ConclusionIn a large nationwide cohort of consecutive patients undergoing CIED surgery, the risk of CSH was 2.5%, with 0.2% necessitating evacuation. CSH risk was increased both in patients receiving aspirin, dual antiplatelet therapy or continued vitamin K‐antagonist therapy. Dual antiplatelet therapy had the highest risk (aOR) of CSH. Both low operator volume and more complex CIED surgery were independently associated with higher CSH risk. These data should be considered when planning CIED surgery.

Hypohomocysteinemia may increases the risk of dementia and Alzheimer's disease: A nationwide population-based prospective cohort study

Hyperhomocysteinemia has been repeatedly found to increase the risk of dementia. However, the effects of hypohomocysteinemia on the risk of dementia have been barely investigated. If hypohomocysteinemia, like hyperhomocysteinemia, increases the risk of dementia, misuse or overuse of homocysteine-lowing agents such as vitamin supplements may increase the risk of dementia. To investigate whether hypohomocysteinemia, like hyperhomocysteinemia, could increase the risk of dementia and Alzheimer's disease (AD) in a large population-based cohort of older adults. This prospective cohort study followed 2655 randomly sampled, community-dwelling, non-demented individuals aged 60 years or older from 2010 to 2018. We measured baseline serum total homocysteine (tHcy) levels and examined the effect of serum tHcy on the risks of dementia and AD using Cox proportional hazards models. During the follow-up period (mean=5.4 years, SD=0.9), dementia and AD developed in 85 and 64 participants, respectively. Not only the participants with high serum tHcy (≥10.6μmol/L) but also those with low serum tHcy (≤8.9μmol/L) were 4-5 times more likely to develop dementia and AD compared to those with serum tHcy levels between 9.0 and 10.5μmol/L. With the increase in serum tHcy concentration, the use of vitamin supplements decreased, and 41.2% of the participants with low serum tHcy (≤8.9μmol/L) were taking vitamin supplements. Not only hyperhomocysteinemia but also hypohomocysteinemia considerably increased the risk of dementia and AD in older adults. The risk of dementia that results from overuse or misuse of vitamin supplements should be acknowledged and homocysteine-lowering health policies should be tailored to consider dementia risks that are associated with hypohomocysteinemia.

Bariatric Surgery and Risk of New-onset Inflammatory Bowel Disease: A Nationwide Cohort Study.

The aim of this study was to examine the risk of new-onset inflammatory bowel disease [IBD] following bariatric surgery. We conducted a nationwide population-based prospective cohort study of the entire Danish population 18 to 60 years of age, alive, and residing in Denmark, from 1996 to 2018. Bariatric surgery was included as a time-dependent variable, and Cox proportional hazards regression models were used to estimate hazard ratios [HRs] of IBD. We used a model adjusting for age, sex, and birth cohort and a multifactor-adjusted model additionally including educational status and number of obesity-related comorbidities. We followed 3 917 843 individuals of whom 15 347 had a bariatric surgery, for development of new-onset IBD. During 106 420 person-years following bariatric surgery, 100 IBD events occurred [incidence rate 0.940/1000 person-years]. During 55 553 785 person-years without bariatric surgery, 35 294 events of IBD occurred [incidence rate 0.635/1000 person-years]. This corresponded to a multifactor-adjusted hazard ratio [HR] of 1.15 (95% confidence interval[CI], 0.94-1.40) for IBD. Multifactor-adjusted HRs of Crohn's disease [CD] and ulcerative colitis [UC] were 1.85 [95% CI, 1.40-2.44] and 0.81 [95% CI, 0.61-1.08], respectively. Among women, the multifactor-adjusted HR for CD was 2.18 [95% CI, 1.64-2.90]. When limiting the study population to individuals with a diagnosis of overweight/obesity, bariatric surgery remained associated with increased risk of CD, multifactor-adjusted HR 1.59 [95% CI, 1.18-2.13]. This nationwide cohort study shows that bariatric surgery is associated with increased risk of development of new-onset CD, but not of UC. The underlying mechanisms remain elusive.

Association Between Metformin Use and Risk of Esophageal Squamous Cell Carcinoma in a Population-Based Cohort Study.

Esophageal cancer is a highly fatal malignant neoplasm, with 2 etiologically different histological types. A large prospective study is expected to elucidate the specific risk of the 90% subtype of esophageal cancer, esophageal squamous cell carcinoma (ESCC), with metformin therapy. This study aims to determine the association between metformin use and incident ESCC risk. This was a nationwide population-based prospective cohort study conducted in Sweden in 2005-2015. Among 8.4 million participants identified in the cohort, 411,603 (5%) were metformin users. The users were compared with 10 times as many frequency-matched nonusers of metformin (n = 4,116,030) by age and sex. Metformin use was treated as a time-varying variate, and multivariable cause-specific proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for ESCC, adjusted for age, sex, calendar year, residence area, tobacco smoking, alcohol overconsumption, and use of nonsteroidal anti-inflammatory drugs or statins. The incidence rates of ESCC were 3.5 per 100,000 person-years among the metformin users and 5.3 per 100,000 person-years in the nonusers. Metformin users overall were at a decreased risk of ESCC compared with nonusers (HR 0.68, 95% CI 0.54-0.85). The decrease in risk was more pronounced in new metformin users (HR 0.44, 95% CI 0.28-0.64) and participants aged 60-69 years (HR 0.45, 95% CI 0.31-0.66). Metformin use decreases the risk of developing ESCC.

Risk of malignancy in patients with psoriasis: a 15-year nationwide population-based prospective cohort study in Korea.

The association between psoriasis and risk of malignancy has not been thoroughly evaluated in a large longitudinal cohort of Asian population. To determine the long-term risk of malignancy in Korean adult patients with psoriasis. We conducted a nationwide population-based prospective cohort study with a 15-year observational period. During the baseline period (1997-2000), total 1773786 Korean subjects who received health insurance from the National Health Insurance System were enrolled and 5788 subjects were defined as a psoriasis group. The number of new-onset malignancy was collected during the observational period (2001-2015). Patients with psoriasis had a higher adjusted hazard ratio (aHR) for development of overall malignancy [aHR 1.08, 95% confidence interval (CI) 1.00-1.18] and gastric cancer (aHR 1.31, 95% CI 1.08-1.58) compared to controls. The risks of non-Hodgkin lymphoma and non-melanoma skin cancer were significantly increased only in patients with psoriasis who received systemic treatments (aHR 2.86, 95% CI 1.07-7.61 and aHR 3.93, 95% CI 1.47-10.47, respectively). Psoriasis is associated with long-term risk for overall malignancy in Koreans, which was primarily driven by the increased risk of gastric cancer.

Increased risk of psoriasis in subjects with abdominal obesity: A nationwide population-based study.

Psoriasis is a chronic inflammatory skin disease known to be associated with a variety of systemic comorbidities, such as metabolic syndrome and obesity. Obesity represents a major comorbidity and has been suggested to be related to psoriasis. This nationwide population-based prospective cohort study was performed to investigate the impacts of body mass index (BMI) and waist circumference (WC) on psoriasis. We used the health check-up database and the study population consisted of subjects who had undergone health screening between January 2009 and December 2012. This study investigated patients newly diagnosed with psoriasis (International Classification of Disease, Tenth Revision, code L40) by dermatologists during the follow-up period (5.32years), based on claims data. The total population consisted of 22633536 subjects, among whom 399461 had newly developed psoriasis. Subjects with BMI of more than 30 had a higher risk of psoriasis (hazards ratio [HR], 1.118; 95% confidence interval [CI], 1.100-1.137) compared with the BMI 18.5-23 group. WC showed a dose-dependent association with psoriatic risk. Subjects with WC over 105cm showed the highest risk of psoriasis (HR, 1.305; 95% CI, 1.261-1.349) compared with subjects with WC lower than 80/75 after adjusting for confounding factors, including BMI. The risk of psoriasis was highest in males with normal BMI and abdominal obesity (HR, 1.175; 95% CI, 1.150-1.200). Our study indicates that WC is a specific factor affecting psoriatic risk and highlights the association between abdominal obesity and psoriasis, thus increasing awareness of the role of abdominal obesity in the pathogenesis and comorbidities of psoriasis.

Decreased risk of esophageal squamous cell carcinoma among metformin users in a population-based cohort study.

e15507 Background: Metformin, mainly used in the treatment of diabetes, may prevent various types of cancer, but no study has specifically examined its potential influence on the risk of esophageal squamous cell carcinoma, the major histological type of esophageal cancer. The aim of this study was to determine the association between metformin use and esophageal squamous cell carcinoma. Methods: This was a nationwide population-based prospective cohort study conducted in Sweden in 2005-2015. Among 8.4 million participants identified from the Swedish Prescribed Drug Registry, 411,603 (5%) were users of metformin. The metformin users were compared with 10 times as many frequency-matched non-users of metformin (n = 4,116,030) by age and sex. Multivariable cause-specific proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, calendar year, place of residence, tobacco smoking, alcohol overconsumption, and use of non-steroidal anti-inflammatory drugs or statins. Results: The incidence rates of esophageal squamous cell carcinoma were 3.5 per 100,000 person-years among the metformin users and 5.3 per 100,000 person-years in the non-users. Metformin users overall were at a decreased risk of esophageal squamous cell carcinoma compared with non-users (adjusted HR 0.68, 95% CI 0.54-0.85). The decrease in risk was more pronounced in new metformin users who were 56 years old when they started their metformin therapy (HR 0.44, 95% CI 0.30-0.65). Conclusions: Metformin therapy may decrease the risk of developing esophageal squamous cell carcinoma.

Thyroid-stimulating hormone and risk of sudden cardiac death, total mortality and cardiovascular morbidity.

Previous data on the association of thyroid function with total mortality, cardiovascular disease (CVD) outcomes and sudden cardiac death (SCD) are conflicting or limited. We investigated associations of thyroid-stimulating hormone (TSH) with these outcomes in a nationwide population-based prospective cohort study. We examined 5211 participants representative of the Finnish population aged ≥30years in 2000-2001 and followed them for a median of 13.2years. Using Cox proportional hazards regression models adjusted for baseline age, gender, smoking, diabetes, systolic blood pressure and total and high-density lipoprotein cholesterol, we assessed the associations of continuous baseline TSH and TSH categories (low [<0.4mU/L], reference range [0.4-3.4mU/L] and high [>3.4mU/L]) with incident total mortality, SCD, coronary heart disease events, stroke, CVD, major adverse cardiac events and atrial fibrillation. High TSH at baseline was related to a greater risk of total mortality (HR 1.34, 95% CI 1.02-1.76) and SCD (HR 2.28, 95% CI 1.13-4.60) compared with TSH within the reference range. High TSH was not associated with the other outcomes (P≥.51), whereas low TSH was not associated with any of the outcomes (P≥.09). TSH at baseline over the full range did not have a linear relation with any of the outcomes (P≥.17). TSH showed a U-shaped association with total mortality after a restricted cubic spline transformation (P=.01). Thyroid function abnormalities could be linked with higher risks of total mortality and SCD. Large-scale randomized studies are needed for evidence-based recommendations regarding treatment of mild thyroid failure.

Gynecological cancer alarm symptoms: is contact with specialist care associated with lifestyle and socioeconomic status? A population-based study.

The aim of this study was to determine the proportion of patients who were referred to specialist care after reporting gynecological cancer alarm symptoms to their general practitioner. We sought to investigate whether contact with specialist care was associated with lifestyle factors or socioeconomic status. Nationwide population-based prospective cohort study in Denmark, based on a random sample of 51 090 women aged 20 years or older from the general population. A web-based questionnaire regarding gynecological alarm symptoms and lifestyle was distributed to the invited individuals. Data about contact with specialist care were obtained from the National Patient Register and the National Health Insurance Service Registry, whereas information about socioeconomic status was collected from Statistics Denmark. Main outcome measures were percentages of patients having contact with specialist care and odds ratios (ORs) for associations between specialist care contact, lifestyle factors and socioeconomic status. The study included 25 866 nonpregnant women; 2957 reported the onset of at least one gynecological cancer alarm symptom, and 683 of these (23.1%) reported symptoms to their general practitioner. The proportion of individuals having contact with specialist care ranged from 39.3% (pain during intercourse) to 47.8% (bleeding during intercourse). Individuals with higher educational level had significantly higher odds of contact with a specialist (OR 1.86, 95% CI 1.17-2.95). Educational level influences contact with specialist care among patients with gynecological cancer alarm symptoms. Future studies should investigate inequalities in access to the secondary healthcare system.

Body mass index and breast cancer: analysis of a nation-wide population-based prospective cohort study on 1 393 985 Taiwanese women.

Background:Asian women have a younger age at onset of breast cancer and a lower body mass index (BMI) than Western women. The link between obesity and risk of breast cancer in Asian women is still elusive. We aimed to investigate the effect of BMI on the risk of incident breast cancer in Taiwanese women.Methods:A total of 1 393 985 women who had been cancer-free before recruitment and attended a nation-wide Taiwanese breast cancer-screening program between 1999 and 2009 were enrolled using a prospective cohort study. Obesity and other relevant variables (such as menopause status and other biochemical markers) were collected through in-person interviews, anthropometric measurements and blood samples at first screen. Incident breast cancers during follow-up were ascertained through the linkage of the cohort with the National Cancer Registry and the National Death Certification System.Results:A total of 6969 and 7039 incident breast cancer cases were identified among women enrolled before and after menopause, respectively. Compared with a BMI range of 18.5–23.9 kg m−2, the incremental level of BMI in the enrolled women before menopause revealed a lack of statistically significant association with the risk of incident breast cancer (adjusted hazard ratio=0.94, 0.98, 1.02, 1.01 and 0.82 for BMI <18.5, 24–26.9, 27–29.9, 30–34.9 and ⩾35, respectively), but the incremental level of BMI in the enrolled women after menopause led to a statistically significant incremental increase in the risk of breast cancer (adjusted hazard ratio=0.78, 1.19, 1.31, 1.53 and 1.65 for BMI <18.5, 24–26.9, 27–29.9, 30–34.9 and ⩾35, respectively) after adjusting for other explanatory risk factors.Conclusion:Obesity acts mainly as an influential promoter of the development of late-onset breast cancer after menopause in Taiwanese women.

Body mass index and breast cancer: a nationwide population-based prospective cohort study on 1,393,985 taiwanese women

Asian women have a younger age at onset of breast cancer and a lower body mass index (BMI) than Western women. The linkage between obesity and the risk of breast cancer in Asian women remains elusive. This study aimed to investigate the effect of BMI on the risk of incident breast cancer in Taiwanese women.

Latent protective effects of breastfeeding on late childhood overweight and obesity: A nationwide prospective study

To investigate the latent effect of breastfeeding on overweight and obesity in late childhood. Data on breastfeeding and child anthropometric measurements were collected annually from a nation-wide population-based prospective cohort study in Japan (21,425 boys and 20,147 girls). Breastfeeding status (exclusiveness and duration) was assessed when the child was 6 months old. Mixed effects models were used to evaluate trajectories of body mass index (BMI), together with overweight and obesity status, from 1.5 to 8 years of age. Mixed-fed boys and exclusively breastfed boys showed lower BMI as the main effect, as well as a slower increase of inclination in BMI as interaction term between feeding type and age, than exclusively formula-fed boys. Breastfed boys had lower BMI at the ages of 7 and 8, in comparison with exclusively formula fed boys (P = 0.002 and P < 0.001, respectively). A similar association was found for girls, although the main effect of feeding type was not statistically significant. The analysis of breastfeeding duration had similar results. Breastfeeding, even if partial or for short duration, has a latent protective effect against overweight and obesity in late childhood, especially for boys.

Increased risk of autism spectrum disorder among early life asthma patients: An 8-year nationwide population-based prospective study

Previous research has suggested an association between autism spectrum disorder (ASD) and allergic disorders, but epidemiological evidence regarding asthma remains limited. We conducted a nationwide population-based prospective cohort study (1:4 case:control patients, age- and gender-matched), hypothesizing that asthma in infancy or toddlerhood increased the risk of ASD. The participants comprised 2134 asthmatic infants and children and 8536 controls aged 0–3 years in 2002. We identified cases of ASD that occurred near the end of the follow-up period (December 31, 2010), determining that asthmatic infants and children exhibited a higher accumulative incidence rate of ASD than did the controls (1.3% vs 0.7%, P=.007). After adjusting for age at enrollment, gender, level of urbanization, and comorbid allergic diseases (i.e., allergic rhinitis and atopic dermatitis), asthmatic infants and children exhibited an elevated risk of developing ASD (hazard ratio: 2.01, 95% confidence interval: 1.19–3.40). This prospective study indicated a temporal relation between asthma and subsequent ASD diagnosis, supporting the immune hypothesis of ASD pathogenesis. Further studies are required to clarify the probable interactional effects between these disorders and define a homogenous ASD subgroup.

Risk of developing diabetes mellitus and hyperlipidemia among patients with bipolar disorder, major depressive disorder, and schizophrenia: A 10-year nationwide population-based prospective cohort study

BackgroundThe high comorbidity of metabolic side effects with severe mental disorders (SMDs), including bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia, had gained much attention, because the excess mortality of these patients is mainly due to physical illness. However, most of these studies were with cross-sectional study design, the time course of metabolic side effects and SMD cannot be elucidated without a cohort study. MethodUsing a nationwide database with a large sample size and a matched control cohort study design, we enrolled patients with SMDs but without diagnoses of and medications for DM and hyperlipidemia from 1996 to 2000, and followed them to the end of 2010. We compared them with age and gender-matched controls (1:4) for the incidence of DM and hyperlipidemia. ResultsThe identified cases were 367 patients with BD, 417 patients with MDD, and 1993 patients with schizophrenia, with average age of 45.3±14.0, 46.5±13.7, and 45.9±12.3, respectively. The patients with BD and schizophrenia had increased risk of initiation of anti-diabetic medications (10.1% vs. 6.3%, p=0.012; 13.3% vs. 7.2% p<0.001; respectively), and anti-hyperlipidemia medications (15.8% vs.10.5%, p=0.004; 14.2% vs.12.1%, p=0.005; respectively) than the controls. After controlling age, gender, urbanization, and income, the Cox regression model showed significantly increased risk of initiation of anti-diabetic medications among patients with BD (hazard ratio (HR) of 1.702, 95% confidence interval (CI): 1.155–2.507) and schizophrenia (HR of1.793, 95% CI: 1.532–2.098). Increased risk of initiation of anti-hyperlipidemia medications was also noted among patients with BD (HR of 1.506, 95% CI: 1.107–2.047) and schizophrenia (HR of 1.154, 95% CI: 1.002–1.329). The patients with MDD did not show increased risk of initiation of these medications than the controls. ConclusionsThis first 10-year nationwide population-based prospective matched control cohort study showed increased risks of initiation of anti-diabetic and anti-hyperlipidemia medications among patients with BD and schizophrenia. No significant increased risk was noted among the patients with MDD.

Allergic rhinitis in adolescence increases the risk of depression in later life: A nationwide population-based prospective cohort study

Background: Many cross-sectional studies have suggested an association between allergic rhinitis (AR) and depression, but the timing relationship was not determined. Using a nationwide population-based prospective cohort study (1:4, age-/gender-matched), we hypothesized that AR in adolescence would increase the risk of depression in later life. MethodsIn all, 1673 adolescents aged 12–15 that had AR between 1996 and 2000 were recruited for our study. Cases of major depressive disorder and any depressive disorder that occurred to the end of follow-up (December 31, 2010) were identified. ResultAdolescents with AR had a higher prevalence of major depression (2.5% vs. 1.2%, p<0.001) and any depressive disorder (4.9% vs. 2.8%, p<0.001) and an earlier onset of major depression (19.31±2.91 vs. 20.43±2.71 years, p=0.038) and any depressive disorder (19.35±2.63 vs. 20.43±2.62 years, p=0.002) compared with the controls. The Cox regression model showed that adolescents with AR had increased HRs of major depression (HR: 1.59, 95% CI: 1.02–2.50) and any depressive disorder (HR: 1.42, 95% CI: 1.04–1.93) after controlling residence location and comorbid allergic diseases. LimitationsThe prevalence of depressive disorder may be underestimated because only those who had medicine-seeking behaviors were enrolled. ConclusionsThis first cohort case–control study showed an association between AR in early adolescence and depression in late adolescence and early adulthood. Our results suggested that allergic responses played important roles in the development of depression.