Population-based Follow-up Study Research Articles

Statin therapy and upper tract urothelial carcinoma risk in hyperlipidemic patients with chronic kidney disease and end-stage kidney disease, a population-based 17-year follow-up study

Background The upper tract urothelial carcinoma (UTUC) risk associated with statin therapy in hyperlipidemic patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) remains obscure. Aim This retrospective cohort study investigated the UTUC risk for hyperlipidemic patients with CKD or ESKD associated with statin therapy. Methods From the national insurance claims data of Taiwan, we identified hyperlipidemic patients and established three pairs of statin users and non-users sub-cohorts matched by propensity scores: 401,490 pairs with normal kidney function, 37,734 pairs with CKD, and 6271 pairs with ESKD. Incidence rates and hazard ratio (HR) of UTUC were estimated, by the end of 2016, between statin and non-statin cohorts, and between hydrophilic statins users and lipophilic statins users. Time-dependent model estimated adjusted HR, and sub-distribution HR (sHR) accounting for the competing risk of deaths. Results The statin-users with ESKD were at increased UTUC risk (sHR 1.98; 95% confidence interval (CI), 1.28–3.06), significant for younger patients (40–64 years). The incidence was twofold greater in women than in men (31.8 versus 15.9 per 10,000 person-years). Receiving lipophilic statins was associated with increased UTUC risk in CKD and ESKD patients, while receiving hydrophilic statins was associated with increased UTUC risk in ESKD patients. Conclusions Patients with ESKD receiving statin were at an increased UTUC risk, significant for younger group (<65 y/o). The positive associations between UTUC and statin persisted in both genders with ESKD, and in therapy with either lipophilic statins or hydrophilic statins. Statin users with ESKD deserve attention for UTUC prevention.

Associations of Habitual Skeletal Loading with Bone Changes During the Menopausal Transition: A Follow-up Study.

While weight-bearing physical activity (PA) benefits bone health, it remains unclear whether PA can counteract hormone-driven menopausal bone deterioration. This secondary analysis of a population-based prospective follow-up study examined changes in bone health indicators around menopause and evaluated whether accelerometer-measured habitual skeletal loading is associated with these changes. A total of 189 initially perimenopausal women without estrogen therapy (mean age 52 [SD 2] years) were followed until they became postmenopausal (mean follow-up time 15 [9] months). Femoral neck bone mineral density (FN BMD) and bone mineral content (BMC) were measured with dual x-ray absorptiometry (DXA). Femoral and tibial shaft volumetric BMD (vBMD), cross-sectional geometry, and stress-strain index (SSI) were assessed using quantitative computed tomography (QCT) in a subset of 61 women. Habitual skeletal loads (mean daily osteogenic index [OI] and low, medium, and high-intensity impact counts) were evaluated with multiple-day free-living accelerometry records. Longitudinal associations of habitual skeletal loads and bone outcomes were analyzed with GEE models. Consistent decreases were observed in FN BMD and BMC, and femoral and tibial shaft vBMD and SSI (p < 0.001) over the follow-up. Slight decreases over the follow-up were also observed in OI and medium impacts in the full sample, and medium and high impact counts in the subsample (p < 0.05). Medium impacts were associated with tibial shaft vBMD and SSI (β = 0.204, 95% CI [0.018, 0.391] and β = 0.077 95% CI [0.000, 0.154], respectively). High impacts were associated with femoral shaft vBMD (β = 0.186 95% CI [0.006, 0.366]. However, no association was observed between habitual skeletal loads and changes in bone characteristics over the follow-up. We observed a rather uniform skeletal response to the menopausal transition at all measured bone sites. Positive associations were found between medium and high-intensity impacts and bone characteristics at the femoral and tibial shafts. However, habitual skeletal loading did not seem to counteract bone deterioration during the menopausal transition.

High-sensitivity cardiac troponin T and N-terminal b-type natriuretic propeptide are associated with cardiac and all-cause mortality in older adults - A population-based ten-year follow-up study.

Cardiac troponin T (cTnT) and N-terminal B-type natriuretic propeptide (proBNP) are mainly used as biomarkers to diagnose specific conditions of the heart, but they also have predictive ability. Our aim was to study their associations with cardiovascular and all-cause mortality in an older population in non-acute conditions. A population-based study with a ten-year follow-up. The data comes from a community-based representative sample of an older population with 1260 participants (participation rate 82 %). Associations were analyzed using Cox proportional hazard models. Altogether, 467 (37%) subjects died during the 10-year follow-up period, and 149 of those of a cardiovascular disease. Both elevated cTnT and proBNP concentrations were statistically significantly associated with cardiovascular and all-cause mortality in older adults. Our study shows that older population with higher cTnT and proBNP concentrations have an increased risk of cardiovascular and all-cause mortality. Acknowledging the elevated risk may aid in targeting follow-up, prevention, and treatment adequately and more individually.

Association Between Disability and Suicide Mortality in the Spanish Community-Dwelling Adult Population. A Population-Based Follow-Up Study.

To assess the association of disability with suicide mortality, separately for women and men by age group. Information was obtained from a representative national sample of 161,809 community-dwelling adults (≥18years). Participants contributed to follow-up time from baseline interview (2008) until suicide, death by other causes, or 2017. We calculated, by sex, standardized suicide mortality differences (SSMD), comparing persons with and without disabilities standardized to sociodemographic distribution of disability population. 29 women died by suicide during 800,754 person-years follow-up and 97 men during 735,709 person-years. Among women with disabilities, SSMD (95% Confidence interval) per 100,000 person-years at 5years was 54.4 deaths (-17.2 to 126.1) [100.0 (-27.4 to 227.4) in women <65years and -4.8 (-27.3 to 17.7) in women ≥65 years (P homogeneity = 0.11)]. Among men, SSMD increased by 122.2 deaths (4.1 to 240.3) [37.2 (-40.2 to 114.6) in men <65years and 74.7 (-51.8 to 200.5) in men ≥65years (P homogeneity = 0.62)]. Suicide risk was higher in women and men with disability. In women higher risk was only notable for those <65. Men presented similar effects in both age groups. Nevertheless, due to imprecision of estimates, results should be viewed cautiously.

Survival among 148 patients with an incidentally detected appendiceal tumours at surgery for acute appendicitis: a population-based cohort follow-up study.

To investigate the long-term prognosis of appendiceal tumours incidentally detected at appendicectomy for suspicion of benign appendicitis. A retrospective register-based single centre cohort study was carried out, using data from the local acute appendicectomy quality register of cases operated on at the Department of Surgery, South General Hospital, Stockholm, Sweden. The local colorectal cancer register was also used to identify appendix tumours. The study period was between January 2004 and January 2023. Survival was calculated according to the Kaplan-Meier method. A total of 11,888 patients were registered in the acute acute appendicectomy register, 54% males and 46% females, median age 32 (Q1 = 21, Q3 = 47) (with 33.7% were 41 years or older). From the appendicectomy and colorectal registers 148 (1.2% of the total cohort) appendiceal tumours were found; 60% in females and 40% in males, median age 56 (Q1 = 43, Q3 = 70) (with 78.4% being 41 years or older). Tumours found were: Low grade Appendiceal Mucinous Neoplasms (LAMN, N = 64); Neuroendocrine Tumours (NET N = 24); adenocarcinomas or other form of carcinomas (N = 57); and adenomas (N = 3). The overall 5-year survival in patients operated for LAMN was 96.8%, for NET 93.3% and for adenocarcinoma 69.7%. The overall 5-year survival for all tumour patients was 85.7%. For the younger patients (< 51 years) with LAMN and NET, almost all survived to the end of follow-up. Survival of patients in the carcinoma group was statistically significantly lower than for the LAMN and NET groups, especially in females 51 years or older. In the group of tumour patients undergoing surgery (n = 146), primary surgery was laparoscopic in 47% and open in 52%. Two patients did not undergo surgery due to widespread disease. In 64% of cases operation was acute, whereas it was delayed and/or planned in 34%. Most procedures were laparoscopic appendicectomy 36%, followed by open appendicectomy 30%, right-sided hemicolectomy 14.6% (open 11.6% and laparoscopic 3%, acute operation 5.5%), ileocaecal resection 5% (acute operation 3.4%), and staging laparoscopy 7%. In 38% of the operated patients the tumour was discovered incidentally at histopathology examination. Two patients had CRS and HIPEC as the initial operation. Forthy-three per cent of the 146 tumour patients operated underwent a second procedure: CRS and HIPEC in 23.3% and right-sided hemicolectomy in 13.6% (laparoscopic 8.2% open 5.4%). Survival was high for patients with incidentally detected appendiceal LAMN or NET, but not so for carcinoma. Survival was lower in the carcinoma group older than 50 years, especially those sick and females.

Atrial fibrillation accelerates functional decline in older adults: a 15-year follow-up population-based study.

Atrial fibrillation (AF) has been associated with functional impairment. However, the role exerted by AF on the long-term trajectories of functional mobility remains to be elucidated. This study aimed to evaluate the impact of AF on functional mobility by tracing walking speed (WS) trajectories over 15 years of follow-up in a population-based cohort of individuals aged 60+ years. This population-based cohort study included 3141 community-dwelling participants (mean age 73.7 years; 63.6% women) from the Swedish National Study on Aging and Care in Kungsholmen, who were regularly examined from 2001-2004 to 2016-2019. Functional mobility was assessed by measuring WS in a standardized way. The association between AF and WS trajectories was assessed by multivariable joint models accounting for the longitudinal dropouts due to death. Stratified analyses by demographic and clinical factors were performed. The effect-modifying role of oral anticoagulant therapy (OAC), incident heart failure (HF), and incident stroke was finally investigated. At baseline, 285 (9.1%) participants were ascertained to have AF. A faster annual WS decline was observed in persons with AF than in non-AF peers (adjusted β coefficient per year = -0.011, 95% confidence interval: -0.016 to -0.005). Incident HF and stroke were associated with greater WS decline in participants with AF. OAC use was not associated with a slower functional decline. Atrial fibrillation is associated with a faster physical function decline in older individuals. Incident HF and stroke possibly accelerate WS decline over time in AF participants.

Patients suffering traumatic brain injury: patient characteristics, prehospital triage, primary referral and mortality - A population-based follow-up study

BackgroundTraumatic brain injury (TBI) is a potential high-risk condition, but appropriate care pathways, including prehospital triage and primary referral to a specialised neurosurgical centre, can improve neurological outcome and survival. The care pathway starts with layman triage, wherein the patient or bystander decides whether to contact a general practitioner (GP) or emergency services (1-1-2 call) as an entryway into the health care system. The GP or 112-health care professional then decides on the level of urgency and dispatches emergency medical services (EMS) when needed. Finally, a decision is made regarding referral of the TBI patient to a specialised neurotrauma centre or a local hospital. Recent studies have shown that injuries are generally more severe in patients entering the health care system through EMS (112-calls) than through GPs; however, no information exists on whether mortality and morbidity outcomes differ depending on the referral choice. The aim of this study was to examine triage pathways, including the method of entry into the health care system, as well as patient characteristics and place of primary referral, to determine the associated 30-day and 1-year mortality rates in TBI patients with confirmed intracranial lesions.MethodsThis retrospective observational population-based follow-up study was conducted in the Central Denmark Region from 1 February 2017 to 31 January 2019. We included all adult patients who contacted hospitals and were ascribed a predefined TBI ICD-10 diagnosis code in the Danish National Patient Register. The obtained TBI cohort was merged with prehospital data from the Prehospital Emergency Medical Services, Central Denmark Region, and vital status from the Danish Civil Registration System. Binary logistic regression analysis of mortality was conducted. In all patients with TBI (including concussions), the primary outcome was primary referral to a specialised centre based on mode of entry (‘GP/HCP’, ‘112-call’ or ‘Unreferred’) into the health care system. In the subgroup of patients with confirmed intracranial lesions, the secondary outcomes were the relative risk of death at day 30 and 1 year based on the place of primary referral.ResultsOf 5,257 first TBI hospital contacts of adult patients included in the cohort, 1,430 (27.2%) entered the health care system via 1-1-2 emergency medical calls. TBI patients triaged by 112-calls were more likely to receive the highest level of emergency response (15.6% vs. 50.3%; p < 0.001) and second-tier resources and were more frequently referred directly to a specialised centre than were patients entering through GPs or other health care personnel. In the subgroup of 1188/5257 (22.4%) patients with confirmed intracranial lesions, we found no difference in the risk ratio of 30 day (RR 1.04 (95%CI 0.65–1.63)) or 1 year (RR 0.96 (95%CI 0.72–1.25)) all-cause mortality between patients primarily referred to a regional hospital or to a specialised centre when adjusting for age, sex, comorbidities, antiplatelet/anticoagulant treatment and type of intracranial lesions.ConclusionTBI patients mainly enter the health system by contact with GPs or other health care professionals. However, patients entering through 112-calls are more frequently triaged directly to specialised centres. We were unable to demonstrate any significant difference in the adjusted 30-day and 1-year mortality based on e primary referral to a specialised centre. The inability to demonstrate an effect on mortality based on primary referral to a specialised centre may reflect a lack of clinical data in the registries used. Considerable differences may exist in nondocumented baseline characteristics (i.e., GCS, blood pressure and injury severity) between the groups and may limit conclusions about differences in mortality. Further research providing high-quality evidence on the effect of primary referral is needed to secure early neurosurgical interventions in TBI patients.

Polycystic ovary syndrome presents as a multimorbid condition by age 50: birth cohort linkage to national register data.

This population-based follow-up study investigated register-based disease diagnoses and medication use up till age of 50 years among women with polycystic ovary syndrome (PCOS) that were identified from a population-based birth cohort. Population-based longitudinal cohort study. Women reporting oligo/amenorrhea and hirsutism at age 31 and/or who were diagnosed with PCOS by a physician by age 46 (n = 244) and women without PCOS symptoms or diagnosis (n = 1556) in the Northern Finland Birth Cohort 1966. National register data on diagnosed diseases (International Statistical Classification of Diseases [ICD]-8-10) and medication use (Anatomical Therapeutic Chemical) until the age of 50. Women with PCOS had a 26% higher risk for any registered diagnosis (risk ratio [RR]: 1.26 [1.09-1.46]) and a 24% higher risk for medication use (RR: 1.24 [1.05-1.46]) compared with non-PCOS women, even after adjusting for several confounders. Several main ICD categories were more prevalent among women with PCOS versus non-PCOS controls, eg, endocrine, metabolic, nervous system, musculoskeletal, and genitourinary diseases in addition with different symptoms and injuries. Surprisingly, even though the overall morbidity was only increased in women with PCOS with a body mass index (BMI) ≥ 25 kg/m2, there were several ICD main categories that showed higher comorbidity risk especially in women with PCOS with a BMI < 25 kg/m2. Several medications were prescribed more often to women with PCOS versus non-PCOS controls, eg, medications related to the alimentary tract and metabolism, the cardiovascular system, genitourinary system drugs and sex hormones, dermatologic and hormonal preparations, and medications to treat the musculoskeletal, nervous, and respiratory systems. Women with PCOS are burdened with multimorbidity and higher medication use, independent of BMI and other confounders. Accordingly, preventive strategies are needed to alleviate the disease burden and improve the health outcomes of women with PCOS.

Risk of diabetes and hypertension in a population with alcohol use disorders

BackgroundA population-based follow-up study assessing the risk of developing hypertension and diabetes associated with alcohol use disorder (AUD) is crucial. We investigated this relationship by using insurance claims data from Taiwan.MethodsFrom the claims data, an AUD cohort (N = 60,590) diagnosed between 2000 and 2006 and a non-AUD comparison cohort (N = 60,590) without the diagnosis of hypertension or diabetes at baseline were established and matched by propensity scores estimated by baseline demographic status and the Charlson comorbidity index (CCI). We assessed the incidence rates of hypertension and/or diabetes at the end of 2016 and used Cox’s method to estimate the related hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsRelative to the comparison cohort, the AUD cohort had an approximately 1.70-fold higher incidence of hypertension (35.1 vs. 20.7 per 1,000 person-years), with an adjusted HR (aHR) of 1.72 (95% CI: 1.68–1.76), 2.16-fold higher incidence of diabetes (20.2 vs. 9.36 per 1,000 person-years), with an aHR of 2.18 (95% CI: 2.11–2.24), and 1.91-fold higher incidence of both diabetes and hypertension (10.3 vs. 5.38 per 1,000 person-years) with an aHR of 2.02 (95% CI: 1.94–2.10). The incidence rates of all outcomes were greater in men than in women, whereas the HRs were greater for AUD in women than for AUD in men relative to the respective comparison patients. The risk increased further for subjects with CCI ≥ 1, which was higher in the AUD cohort.ConclusionsThe increased risk of developing diabetes and hypertension in patients with AUD, especially the differences noted according to gender, indicates that clinicians should address potential comorbidities in these patients.

Physical activity and the risk of chronic obstructive pulmonary disease: A longitudinal follow-up study in Taiwan

BackgroundThis study aimed to investigate whether physical activity (PA) is associated with a lower risk of subsequently developing chronic obstructive pulmonary disease (COPD). MethodsWe conducted this population-based longitudinal follow-up study in a community in Taiwan. This study recruited 61,446 subjects who had participated in the Keelung Community-based Integrated Screening Program (KCIS) between 2005 and 2012. During their participation in KCIS, they were provided with structured questionnaires to collect their baseline characteristics, including weekly PA time. After excluding subjects diagnosed with COPD before they joined KCIS and/or who provided incomplete lifestyle data, 59,457 subjects remained, and were classified into three groups based on their weekly PA time: i.e., as NPA (no regular PA), LPA (low PA, <90 min/week) and HPA (high PA, ≥90 min/week). The primary outcome was a new diagnosis of COPD, followed up until the end of 2015 or their death. Cox proportional-hazard regression was used to assess the impact of PA on the risk of COPD. ResultsThe risk of COPD was more than 20% lower in the LPA and HPA groups than in the NPA group. Specifically, the adjusted hazard ratio for the risk of COPD was 0.72 in the LPA group (95% CI, 0.61-0.85, p < 0.001) and 0.79 in the HPA group (95% CI, 0.69-0.90, p < 0.001). ConclusionsOur research uncovered an inverse relationship between PA and COPD. The findings suggest that PA might be useful as a strategy for the primary prevention of COPD.

Physical activity and the risk of ischemic stroke: A population-based longitudinal follow-up study in Taiwan (KCIS no. 43)

Lack of exercise is a leading risk factor for stroke, and it has been demonstrated that increasing physical activity (PA) can prevent ischemic stroke. However, there has been limited research on the relationship between ischemic stroke and PA, especially among Asian populations. This study therefore investigates whether the level of PA in the Taiwanese population affects its risk of first-ever ischemic stroke, utilizing screening data on 58,857 individuals collected by the Keelung Health Bureau between 2005 and 2012. These subjects were divided into three groups based on their weekly exercise frequency and duration, i.e., 1) a no PA (NPA) group, 2) a low PA (LPA) group (less than 90 min of exercise per week), and 3) a high PA (HPA) group (90 min or more of exercise per week). The results showed that, as compared to the NPA group, the adjusted hazard ratio for ischemic stroke in the LPA group was 0.86 (95 % CI, 0.78–0.95, p < 0.0001); and that in the HPA group, it was also 0.86 (95 % CI, 0.79–0.94, p < 0.0001). In other words, even engaging in PA for less than 90 min per week may lower the risk of first-ever ischemic stroke. Importantly, LPA is more accessible, more sustainable, and easier to promote for the general population than the 150 min per week recommended by the World Health Organization.

Headache disorders and risk of stroke: A register-linked HUNT study

Background Many studies have found that migraine with aura (MA) is a risk factor of stroke, but the relationship between stroke and migraine without aura and tension-type headache is unclear. The aim of this study was to investigate whether primary headache disorders, including subtypes of migraine, increase the risk of ischemic or hemorrhagic stroke. Methods This large population-based 13-year follow-up study used baseline headache data from the third Trøndelag Health Study (HUNT3) performed between 2006 and 2008. The HUNT3 headache data were linked to the Norwegian National Stroke Register that includes stroke diagnoses recorded from 2013 until December 2021. The association between stroke and headache status was investigated in individuals aged ≥20 years without stroke at baseline. Prospective associations were evaluated using multivariable Cox proportional hazard models with 95% confidence intervals. Separate sub-group analyses by age and sex were performed. Results Among 37,364 included participants, 50% were younger than 55 years. A total of 1095 (2.9%) developed stroke after a median of 9 years. In the multi-adjusted model, reporting MA at baseline was associated with increased risk of stroke at follow-up (HR 1.59, 95% CI 1.14–2.21) compared with those without headache. The increased risk of stroke was most evident among individuals &lt;55 years with MA (HR 2.18, 95% CI 1.24–3.82) and among women (HR 1.70, 95% CI 1.12–2.59). Migraine without aura (MO), tension-type headache (TTH) and unclassified headaches were not associated with increased risk of stroke. Conclusions During 15 years of follow-up, individuals with MA were more likely to suffer from stroke compared to those without headache. The relationship with MA was even stronger in women, and for young individuals aged &lt;55 years. Individuals with MO or TTH were not associated with increased risk of stroke.

Relationship between hysterectomy and global DNA methylation levels in peripheral blood: an exploratory follow-up study

ObjectiveThe present study aims to understand the relationship between hysterectomy and peripheral blood leukocyte (PBL) global DNA methylation independently and in light of selected biochemicals (vitamin B12, folate, homocysteine). Material and methodsFor the present population-based follow-up study, a total of 616 women aged 30–70 years were recruited from Haryana, India. Recruited participants underwent a baseline assessment, which included the determination of menopausal and hysterectomy status and estimation of vitamin B12, folate, homocysteine, and PBL global DNA methylation (5mC) levels. The 5mC levels were analyzed using ELISA-based colorimetric technique. Participants with no history of hysterectomy were followed up after 8 years, and their current menopausal and hysterectomy statuses were determined. ResultThe median PBL 5mC level of the group with hysterectomy was found to be significantly lower than that of those without hysterectomy in the baseline assessment (PBL 5mC = 0.47 vs. 0.74, respectively; p-value = 0.016). However, there was no significant difference in baseline median PBL 5mC levels between women who eventually underwent hysterectomy and those who did not. When stratified for biochemical levels, the trend of PBL global DNA hypomethylation in the hysterectomy group, compared to the no-hysterectomy group, was statistically significant only within the normal folate group. ConclusionThis study suggests a potential association between hysterectomy (or related factors) and global DNA hypomethylation. Further research is warranted to validate the findings of the present study and to advance the existing knowledge regarding the epigenetic implications of hysterectomy.

Incidence Rates and Risk Ratios of Normal Tension Glaucoma in Patients with Chronic Rhinosinusitis: A Population-Based Longitudinal Follow-Up Study.

Several studies have investigated the association between chronic rhinosinusitis (CRS) and ophthalmological complications. However, it remains uncertain whether CRS is independently associated with the development of normal tension glaucoma (NTG). Therefore, this retrospective cohort study aimed to investigate the prospective association between CRS and the increased incidence and risk of NTG using a representative population-based dataset. The selection of both the CRS and comparison groups was meticulously conducted through the propensity scoring method. The incidence and risk ratios of NTG were measured using person-years at risk and a weighted Cox proportional hazards model. We enrolled 30,284 individuals without CRS (comparison group) and 15,142 individuals with CRS. The NTG incidence rates were 1.19 and 0.81 in the CRS and comparison groups, respectively. The CRS group showed a significantly increased risk of subsequent development for NTG (adjusted hazard ratio = 1.41, 95% confidence interval = 1.16-1.72), regardless of the CRS subtype. Additionally, the risk of developing NTG was relatively higher in the first 2 years after CRS diagnosis. Moreover, a subgroup analysis revealed a higher risk of NTG in elderly female individuals with CRS. The present findings underscore the importance of monitoring and managing NTG risk in individuals with CRS, especially in elderly female patients.

Maternal pre-pregnancy BMI and reproductive health in adult sons: a study in the Danish National Birth Cohort.

Is maternal pre-pregnancy BMI associated with semen quality, testes volume, and reproductive hormone levels in sons? Maternal pre-pregnancy BMI was associated with an altered reproductive hormone profile in young adult sons, characterized by higher levels of oestradiol, LH, and free androgen index (FAI) and lower levels of sex hormone-binding globulin (SHBG) in sons born of mothers with pre-pregnancy overweight and obesity. Evidence suggests that maternal pre-pregnancy BMI may influence reproductive health later in life. Only one pilot study has investigated the association between maternal pre-pregnancy BMI and reproductive health outcomes in sons, suggesting that a high BMI was associated with impaired reproductive function in the adult sons. A population-based follow-up study of 1058 young men from the Fetal Programming of Semen Quality (FEPOS) cohort nested within the Danish National Birth Cohort (DNBC), 1998-2019, was carried out. In total, 1058 adult sons (median age 19 years, 2 months), born 1998-2000 by mothers included in the DNBC, participated in FEPOS. At a clinical examination, they provided a semen and blood sample, measured their testes volume, and had height and weight measured. Maternal pre-pregnancy BMI was obtained by self-report in early pregnancy. Semen characteristics, testes volume, and reproductive hormone levels were analysed according to maternal pre-pregnancy BMI categories and as restricted cubic splines using negative binomial and ordinary least square regression models. Mediation analyses examined potential mediation by the sons' birthweight, pubertal timing, fat mass, and BMI. Additional analyses investigated the role of paternal BMI in the potential associations between maternal BMI and reproductive health outcomes. We found no consistent associations between maternal pre-pregnancy BMI and semen characteristics or testes volume. Sons of mothers with higher pre-pregnancy BMI had higher oestradiol and lower SHBG levels, both in a dose-dependent manner. Sons of mothers with pre-pregnancy obesity (≥30 kg/m2) had higher LH levels and a higher FAI than sons born by mothers with normal pre-pregnancy BMI (18.5-24.9 kg/m2). The mediation analyses suggested that the effect of maternal pre-pregnancy BMI on higher levels of oestrogen, LH, and FAI was partly mediated by the sons' birthweight, in addition to adult fat mass and BMI measured at the clinical examination, whereas most of the effect on lower levels of SHBG was primarily mediated by the sons' own fat mass and BMI. Paternal BMI was not a strong confounder of the associations in this study. This study was based in a population-based cohort with a low prevalence of overweight and obesity in both mothers and adult sons. Some men (10%) had blood for reproductive hormone assessment drawn in the evening. While several potential confounding factors were accounted for, this study's inherent risk of residual and unmeasured confounding precludes provision of causal estimates. Therefore, caution should be given when interpreting the causal effect of maternal BMI on sons' reproductive health. Given the widespread occurrence of overweight and obesity among pregnant women, it is imperative to thoroughly examine the potential consequences for reproductive hormone levels in adult sons. The potential effects of maternal pre-pregnancy obesity on sons' reproductive hormone profile may potentially be partly avoided by the prevention of overweight and obesity in the sons. The project was funded by the Lundbeck Foundation (R170-2014-855), the Capital Region of Denmark, Medical doctor Sofus Carl Emil Friis and spouse Olga Doris Friis's Grant, Axel Muusfeldt's Foundation (2016-491), AP Møller Foundation (16-37), the Health Foundation, Dagmar Marshall's Fond, Aarhus University, Independent Research Fund Denmark (9039-00128B), and the European Union (ERC, BIOSFER, 101071773). Views and opinions expressed are, however, those of the authors only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible. The authors declare that they have no conflict of interest. N/A.

Maternal Intake of Vitamin D Supplements during Pregnancy and Pubertal Timing in Children: A Population-Based Follow-Up Study.

Maternal vitamin D may be important for several organ systems in the offspring, including the reproductive system. In this population-based follow-up study of 12,991 Danish boys and girls born 2000-2003, we investigated if maternal intake of vitamin D supplements during pregnancy was associated with pubertal timing in boys and girls. Information on maternal intake of vitamin D supplements was obtained by self-report in mid-pregnancy. Self-reported information on the current status of various pubertal milestones was obtained every six months throughout puberty. Mean differences in months at attaining each pubertal milestone and an average estimate for the mean difference in attaining all pubertal milestones were estimated according to maternal intake of vitamin D supplements using multivariable interval-censored regression models. Lower maternal intake of vitamin D supplements was associated with later pubertal timing in boys. For the average estimate, boys had 0.5 months (95% CI 0.1; 0.9) later pubertal timing per 5 µg/day lower maternal vitamin D supplement intake. Maternal intake of vitamin D supplements was not associated with pubertal timing in girls. Spline plots and sensitivity analyses supported the findings. Whether the observed association with boys' pubertal timing translates into an increased risk of disease in adulthood is unknown.

Treatment and Survival Among Patients With Colorectal Cancer in Sub-Saharan Africa: A Multicentric Population-Based Follow-Up Study.

The burden of colorectal cancer (CRC) is increasing in Sub-Saharan Africa (SSA). However, little is known about CRC treatment and survival in the region. A random sample of 653 patients with CRC diagnosed from 2011 to 2015 was obtained from 11 population-based cancer registries in SSA. Information on clinical characteristics, treatment, and/or vital status was obtained from medical records in treating hospitals for 356 (54%) of the patients ("traced cohort"). Concordance of CRC treatment with NCCN Harmonized Guidelines for SSA was assessed. A Cox proportional hazards model was used to examine the association between survival and human development index (HDI). Of the 356 traced patients with CRC, 51.7% were male, 52.8% were from countries with a low HDI, 55.1% had colon cancer, and 73.6% were diagnosed with nonmetastatic (M0) disease. Among the patients with M0 disease, however, only 3.1% received guideline-concordant treatment, 20.6% received treatment with minor deviations, 31.7% received treatment with major deviations, and 35.1% received no treatment. The risk of death in patients who received no cancer-directed therapy was 3.49 (95% CI, 1.83-6.66) times higher than in patients who received standard treatment or treatment with minor deviations. Similarly, the risk of death in patients from countries with a low HDI was 1.67 (95% CI, 1.07-2.62) times higher than in those from countries with a medium HDI. Overall survival at 1 and 3 years was 70.9% (95% CI, 65.5%-76.3%) and 45.3% (95% CI, 38.9%-51.7%), respectively. Fewer than 1 in 20 patients diagnosed with potentially curable CRC received standard of care in SSA, reinforcing the need to improve healthcare infrastructure, including the oncology and surgical workforce.

Long-term Risk of Epilepsy in Subarachnoid Hemorrhage Survivors With Positive Family History: A Population-Based Follow-up Study.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of stroke affecting the working-age population, where epilepsy is a common complication and major prognostic factor for increased morbidity in aSAH survivors. The objective of this analysis was to assess whether epilepsy in first-degree relatives is a risk of developing epilepsy after aSAH. We used a region-specific database that includes all cases of unruptured and ruptured saccular intracranial aneurysm admitted to Kuopio University Hospital from its defined Eastern Finnish catchment population. We also retrieved data from Finnish national health registries for prescription drug purchases and reimbursement, hospital discharge, and cause of death and linked them to patients with aSAH, their first-degree relatives, and population controls matched 3:1 by age, sex, and birth municipality. Cox regression modeling and Kaplan-Meier survival curves were used for analysis. We examined data for 760 consecutive 12-month survivors of aSAH, born in 1950 or after, with a first aSAH from January 1, 1995, to December 31, 2018. Of the 760 patients (median age, 47 years; 53% female; median follow-up, 11 years), 111 (15%) developed epilepsy at a median of 7 months (interquartile range, 2-14 months) after admission for aSAH. Of the 2,240 population controls and 4,653 first-degree relatives of patients with aSAH, 23 (0.9%) and 80 (1.7%), respectively, developed epilepsy during the follow-up period. Among 79 patients with epilepsy in first-degree relatives, 22 (28%) developed epilepsy after aSAH; by contrast, among 683 patients with no epilepsy in first-degree relatives, 89 (13%) developed epilepsy after aSAH. Having at least 1 relative with epilepsy was an independent risk factor of epilepsy after aSAH (hazard ratio, 2.44; 95% CI 1.51-3.95). Cumulative 1-year rates by first-degree relationship were 40% with 1 or more children with epilepsy, 38% with 1 or more affected parents, 5% with 1 or more affected siblings, and 10% with no relatives with epilepsy. Patients who developed epilepsy after aSAH were significantly more likely to have first-degree relatives with epilepsy than those who did not develop epilepsy after the aSAH.

Cancer Risk in Elderly Korean Patients with Neurodegenerative Disease and its relation to Type 2 Diabetes

Introduction: Some studies suggest that neurodegenerative diseases (NDs), cancer, and type 2 diabetes (T2D) are all related to protein misfolding and may be linked. This study aimed to determine whether these diseases are associated with each other. Objective: The aim of the study was to investigate the difference in cancer incidence according to the presence or absence of T2D in the ND group and the control group during the 10-year follow-up period. Methods: A population-based 10-year follow-up study was conducted using the Korean National Health Insurance Service Database between 2002 and 2015. The study population included the ND group (n = 9,292) and the control group (n = 46,742), who were aged 60 to 84 years. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HRs) for cancer. Results: ND and/or T2D were newly diagnosed in both groups during the follow-up period. The newly diagnosed ND cases before cancer onset were 2,412 (26.0%) and 15,435 (33.0%) in the ND and control groups, respectively (p &lt; 0.01). The newly diagnosed T2D cases were 4,691 (50.5%) and 25,695 (55.0%) in the ND and control groups, respectively (p &lt; 0.01). At the end of the observation period, the number of cancer patients was 2,040 (22.0%) and 8,628 (18.5%) in the ND and control groups, respectively (p &lt; 0.01). The ND group was associated with an increased risk of cancer (HR = 1.25). In both groups, newly diagnosed ND and T2D showed an additive effect on cancer incidence during the follow-up period. Conclusion: This study showed that cancer incidence was positively associated with ND and T2D. These results show that ND, cancer, and T2D are related. More replication studies are needed to address the association between ND, cancer, and T2D.

Adhesive capsulitis of the shoulder is associated with an increased risk for Parkinson's disease: a population-based longitudinal follow-up study.

Previous studies have suggested a positive association between adhesive capsulitis of the shoulder (ACS) and Parkinson's disease (PD), but longitudinal data were lacking. The present population-based longitudinal follow-up study therefore investigated the risk of developing PD in patients with ACS. This study utilized data from Taiwan's Longitudinal Health Insurance Database 2005 (LHID 2005). We defined our ACS group as the 19,920 patients aged between 40 and 79 who had been diagnosed with ACS between 2002 and 2006. The non-ACS group consisted of an age- and sex-matched but otherwise random selection of 19,920 patients without a diagnosis of ACS. The Kaplan-Meier method was then used to examine inter-group differences in PD-free survival rates, and Cox proportional-hazard regression modeling was used to evaluate the impact of ACS on PD risk. During a median follow-up period of 105 months, 242 subjects in the ACS group and 208 subjects in the non-ACS group developed PD. The adjusted hazard ratio (HR) of 1.53 (1.26-1.86) indicated that ACS patients had a significantly higher risk of developing PD than their non-ACS counterparts, regardless of sex and age. Landmark analysis that excluded PD cases detected within the first 2 years after an ACS diagnosis showed that the HR was almost unchanged, at 1.56 (1.26-1.95). Patients with ACS are at a high risk of developing PD. • This population-based study showed that adhesive capsulitis of the shoulder (ACS) is associated with a higher risk of Parkinson's disease (PD). • This study broke new ground by using a longitudinal follow-up design and a nationally representative sample. • Our findings suggest that clinicians who care for ACS patients need to be aware of this increased risk of developing PD.