Large-scale Population-based Cohort Study Research Articles

Anthropometric Trajectories in Children Prior to Development of Inflammatory Bowel Disease

Poor nutrition and growth in childhood have short-term and long-term consequences, so understanding the timing of the onset of an impaired nutritional status is crucial for diagnosing and treating inflammatory bowel disease (IBD) at its earliest stage. To assess anthropometric trajectories before a pediatric diagnosis of IBD and growth recovery after diagnosis. This population-based cohort study included children born in Denmark from January 1, 1997, through December 31, 2015, with weight and length or height measurements at birth and at least 1 length or height and weight measurement at school age based on the Danish Medical Birth Register and the Danish National Child Health Register. Within this population, all individuals diagnosed with IBD at ages 5 to 17 years, according to the Danish National Patient Register, were identified. Data were analyzed from October 13, 2023, to April 17, 2024. A pediatric diagnosis of IBD compared with the corresponding population without the disease. The outcome measures were z scores for length or height, weight, and body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) before and after pediatric IBD diagnosis compared with reference and sibling populations. The final study population included 916 133 individuals (51.2% male) with a median of 3 pairs of length or height and weight measurements collected (IQR, 2-6 pairs). Of those, 1522 (median age, 14.3 years [IQR, 11.8-16.3 years]; 763 female [50.1%]) were diagnosed with IBD (851 [55.9%] with Crohn disease [CD] and 671 [44.1%] with ulcerative colitis [UC]). Compared with children without IBD, individuals with a later diagnosis of CD had declining anthropometric measures 3 years (weight: mean, -0.12 g [95% CI, -0.20 to -0.03 g]; BMI: mean, -0.13 [95% CI, -0.21 to -0.04]) and 1 year (length or height: mean, -0.20 cm [95% CI, -0.29 to -0.10 cm]) prior to diagnosis, whereas this was observed 1 year prior to a diagnosis of UC for weight (mean, -0.12 g [95% CI, -0.22 to -0.02 g]) and BMI (mean, -0.13 [95% CI, -0.23 to -0.03]). Deviating anthropometric patterns persisted after diagnosis, with the slowest recovery observed in children with CD. The findings of this large-scale population-based cohort study of anthropometrics in children suggest impaired nutritional status as assessed by weight up to 3 years and by length or height 1 year before a diagnosis of CD and by weight up to 1 year before a diagnosis of UC. These findings emphasize that the onset of pediatric IBD may occur years prior to diagnosis, that growth recovery may first occur after diagnosis and treatment, and that frequent nutritional screenings may help ensure a healthy transition to adulthood.

The long-term survival outcome of sporadic bilateral renal cell carcinoma and optimization of surgical treatment: a large-scale population-based cohort study

Sporadic bilateral renal cell carcinoma (BRCC) is a rare situation of RCC. The treatment for BRCC is controversial and there is a lack of authoritative guidelines about the management of BRCC. Patients diagnosed with sporadic BRCC between 2004 and 2020 were identified from Surveillance, Epidemiology, and End Results (SEER) database. The primary outcome was overall survival (OS). Kaplan–Meier survival analysis, Cox regression analysis, and competing risk regression models were used to compare survival outcomes and identify prognostic factors. A total of 20,523 patients (16,534 unilateral RCC [URCC] patients and 3989 BRCC patients) were included. The prognosis of BRCC patients is between metastatic and non-metastatic URCC patients. 3677 patients were diagnosed with localized BRCC (2180 synchronous BRCC patients and 1497 metachronous BRCC patients). Compared with metachronous BRCC, synchronous BRCC patients had relatively poor OS. However, the CSS was similar. Partial nephrectomy (PN) leads to the best OS and provides equivalent oncological outcomes to radical nephrectomy. Local tumor destruction (LTD) could also achieve an acceptable cancer-control effect. Then we developed treatment flowchart for localized BRCC patients. Additionally, we identified the prognostic factors, and analyzed the association between factors using the multivariable Cox regression method. PN should be the initial treatment for sporadic localized BRCC patients if feasible. LTD could be considered as an effective treatment alternative. This study could provide evidence for the optimization of individualized treatment for sporadic BRCC patients.Trial registration: The trial was registered on the ClinicalTrials.gov (NCT06369519).

Hypothalamic volume is associated with age, sex and cognitive function across lifespan: a comparative analysis of two large population-based cohort studies.

Emerging findings indicate that the hypothalamus, the body's principal homeostatic centre, plays a crucial role in modulating cognition, but comprehensive population-based studies are lacking. We used cross-sectional data from the Rhineland Study (N=5812, 55.2±13.6 years, 58% women) and the UK Biobank Imaging Study (UKB) (N=45,076, 64.2±7.7 years, 53% women), two large-scale population-based cohort studies. Volumes of hypothalamic structures were obtained from 3T structural magnetic resonance images through an automatic parcellation procedure (FastSurfer-HypVINN). The standardised cognitive domain scores were derived from extensive neuropsychological test batteries. We employed multivariable linear regression to assess associations of hypothalamic volumes with age, sex and cognitive performance. In older individuals, volumes of total, anterior and posterior hypothalamus, and mammillary bodies were smaller, while those of medial hypothalamus and tuberal region were larger. Larger medial hypothalamus volume was related to higher cortisol levels in older individuals, providing functional validation. Volumes of all hypothalamic structures were larger in men compared to women. In both sexes, larger volumes of total, anterior and posterior hypothalamus, and mammillary bodies were associated with better domain-specific cognitive performance, whereas larger volumes of medial hypothalamus and tuberal region were associated with worse domain-specific cognitive performance. We found strong age and sex effects on hypothalamic structures, as well as robust associations between these structures and domain-specific cognitive functions. Overall, these findings thus implicate specific hypothalamic subregions as potential therapeutic targets against age-associated cognitive decline. Institutional funds, Federal Ministry of Education and Research of Germany, Alzheimer's Association.

COVID-19 infection is associated with an elevated risk for autoimmune blistering diseases while COVID-19 vaccination decreases the risk: A large-scale population-based cohort study of 112 million individuals

Numerous diseases associated with COVID-19 infection and vaccination have been reported, including conditions such as the autoimmune blistering diseases (AIBD) pemphigus and pemphigoid. However, robust evidence supporting these associations is lacking. To investigate the risk of developing AIBD following COVID-19 infection and vaccination. Population-based retrospective cohort study utilizing data from over 112 million patients. The risk of AIBD within three months was compared among three cohorts: COVID-19 infection, COVID-19 vaccination, and controls, along with seven sensitivity analyses. COVID-19 infection was associated with an increased risk of AIBD (HR 1.508, 95% CI 1.260-1.805), with the risk being more pronounced for pemphigus (HR 2.432, 1.618-3.657) compared to bullous pemphigoid (HR 1.376, 1.019-1.857). Conversely, COVID-19 vaccination was associated with an almost halved risk of AIBD (HR 0.514, 0.394-0.672), with the risk reduction most significant for pemphigus (HR 0.477, 0.241-0.946). Comparisons between COVID-19 infection and vaccination revealed a more than threefold increased risk of AIBD in the infection cohort (HR 3.130, 2.411-4.063), particularly for pemphigus (HR 5.508, 2.973-10.205). Retrospective design and potential underreporting of COVID-19 cases and vaccinations. COVID-19 infection significantly increases the risk of AIBD while vaccination appears to reduce this risk.

All-cause and cause-specific mortality risks in individuals with diabetes living alone: A large-scale population-based cohort study

AimsThe rise in one-person households is a global trend. We aimed to investigate mortality risk in individuals with diabetes living alone (IDLA) using a large-scale population-based database. MethodsA total of 2,447,557 adults with type 2 diabetes were identified from the Korean National Health Information Database. One-person households were defined based on the number of registered family members. The risks of all-cause and cause-specific mortalities were estimated using a multivariable Cox proportional hazards regression model. ResultsDuring a median follow-up period of 6.0 years, 191,084 deaths (7.8 %) occurred. IDLA had a higher risk of mortality compared to those not living alone after adjusting for potential confounders (HR 1.20, 95 % CI: 1.18–1.22). This association was more prominent in younger individuals, men, and those with low income, and it was dependent on the duration of living alone. The risks of cause-specific mortality were all significantly higher in the IDLA group compared with the non-IDLA group. Adherence to favorable lifestyle behaviors was associated with a significant reduction in all-cause mortality, particularly in IDLA. ConclusionsThe elevated risk of mortality in IDLA highlights the need for tailored medical interventions and social assistance, particularly for those with unhealthy lifestyles or low income.

Osteoporosis, spinal degenerative disorders, and their association with low back pain, activities of daily living, and physical performance in a general population

Osteoporosis, vertebral fractures, and spinal degenerative diseases are common conditions that often coexist in older adults. This study aimed to determine the factors influencing low back pain and its impact on activities of daily living (ADL) and physical performance in older individuals with multiple comorbidities. This cross-sectional study was part of a large-scale population-based cohort study in Japan, involving 1009 participants who underwent spinal magnetic resonance imaging (MRI) to assess cervical cord compression, radiographic lumbar spinal stenosis, and lumbar disc degeneration. Vertebral fractures in the thoracolumbar spine were evaluated using sagittal MRI with a semi-quantitative method. Bone mineral density was measured using dual-energy X-ray absorptiometry. Low back pain, Oswestry Disability Index (ODI), and physical performance tests, such as one-leg standing time, five times chair-stand time, maximum walking speed, and maximum step length, were assessed. Using clinical conditions as objective variables and image evaluation parameters as explanatory variables, multiple regression analysis showed that vertebral fractures were significantly associated with low back pain and ODI. Vertebral fractures and osteoporosis significantly impacted physical performance, whereas osteoporosis alone did not affect low back pain or ODI. Our findings contribute to new insights into low back pain and its impact on ADL and physical performance.

Identifying early language predictors: A replication of Gasparini etal. (2023) confirming applicability in a general population cohort.

Identifying language disorders earlier can help children receive the support needed to improve developmental outcomes and quality of life. Despite the prevalence and impacts of persistent language disorder, there are surprisingly no robust predictor tools available. This makes it difficult for researchers to recruit young children into early intervention trials, which in turn impedes advances in providing effective early interventions to children who need it. To validate externally a predictor set of six variables previously identified to be predictive of language at 11 years of age, using data from the Longitudinal Study of Australian Children (LSAC) birth cohort. Also, to examine whether additional LSAC variables arose as predictive of language outcome. A total of 5107 children were recruited to LSAC with developmental measures collected from 0 to 3 years. At 11-12 years, children completed the Clinical Evaluation of Language Fundamentals, 4th Edition, Recalling Sentences subtest. We used SuperLearner to estimate the accuracy of six previously identified parent-reported variables from ages 2-3 years in predicting low language (sentence recall score ≥ 1.5 SD below the mean) at 11-12 years. Random forests were used to identify any additional variables predictive of language outcome. Complete data were available for 523 participants (52.20% girls), 27 (5.16%) of whom had a low language score. The six predictors yielded fair accuracy: 78% sensitivity (95% confidence interval (CI) = [58, 91]) and 71% specificity (95% CI = [67, 75]). These predictors relate to sentence complexity, vocabulary and behaviour. The random forests analysis identified similar predictors. We identified an ultra-short set of variables that predicts 11-12-year language outcome with 'fair' accuracy. In one of few replication studies of this scale in the field, these methods have now been conducted across two population-based cohorts, with consistent results. An imminent practical implication of these findings is using these predictors to aid recruitment into early language intervention studies. Future research can continue to refine the accuracy of early predictors to work towards earlier identification in a clinical context. What is already known on the subject There are no robust predictor sets of child language disorder despite its prevalence and far-reaching impacts. A previous study identified six variables collected at age 2-3 years that predicted 11-12-year language with 75% sensitivity and 81% specificity, which warranted replication in a separate cohort. What this study adds to the existing knowledge We used machine learning methods to identify a set of six questions asked at age 2-3 years with ≥ 71% sensitivity and specificity for predicting low language outcome at 11-12 years, now showing consistent results across two large-scale population-based cohort studies. What are the potential or clinical implications of this work? This predictor set is more accurate than existing feasible methods and can be translated into a low-resource and time-efficient recruitment tool for early language intervention studies, leading to improved clinical service provision for young children likely to have persisting language difficulties.

Risk of Cardiovascular Events Associated with Chronic Obstructive Pulmonary Disease and/or Metabolic Syndrome: A Large-Scale Nationwide Population-Based Cohort Study.

Chronic obstructive pulmonary disease (COPD) and metabolic syndrome (MetS) are among the most prevalent conditions that might predispose individuals to life-threatening events. We aimed to examine their associations with cardiovascular (CV) events and mortality using a large-scale population dataset from the National Health Information Database in Korea. This population-based cohort study enrolled adults aged ≥40 years who had undergone more than two health examinations between 2009 and 2011. They were divided into four groups based on the presence of COPD and MetS. Analysis of the outcomes and CV events or deaths was performed from 2014 to 2019. We compared CV event incidence and mortality rates using a multivariate Cox proportional hazards model and Kaplan-Meier curves. Totally, 5,101,810 individuals were included, among whom 3,738,458 (73.3%) had neither COPD nor MetS, 1,193,014 (23.4%) had only MetS, 125,976 (2.5%) had only COPD, and 44,362 (0.9%) had both. The risk of CV events was significantly higher in individuals with both COPD and MetS than in those with either COPD or MetS alone (HRs: 2.4 vs 1.6 and 1.8, respectively; all P <0.001). Similarly, among those with both COPD and MetS, all-cause and CV mortality risks were also elevated (HRs, 2.9 and 3.0, respectively) compared to the risks in those with either COPD (HRs, 2.6 and 2.1, respectively) or MetS (HRs, 1.7 and 2.1, respectively; all P <0.001). The comorbidity of MetS in patients with COPD increases the incidence of CV events and all-cause and cardiovascular mortality rates.

Multimorbidity patterns and trajectories in young and middle-aged adults: a large-scale population-based cohort study.

The presence of multiple chronic conditions, also referred to as multimorbidity, is a common finding in adults. Epidemiologic research can help identify groups of individuals with similar clinical profiles who could benefit from similar interventions. Many cross-sectional studies have revealed the existence of different multimorbidity patterns. Most of these studies were focused on the older population. However, multimorbidity patterns begin to form at a young age and can evolve over time following distinct multimorbidity trajectories with different impact on health. In this study, we aimed to identify multimorbidity patterns and trajectories in adults 18-65 years old. We conducted a retrospective longitudinal epidemiologic study in the EpiChron Cohort, which includes all inhabitants of Aragón (Spain) registered as users of the Spanish National Health System, linking, at the patient level, information from electronic health records from both primary and specialised care. We included all 293,923 patients 18-65 years old with multimorbidity in 2011. We used cluster analysis at baseline (2011) and in 2015 and 2019 to identify multimorbidity patterns at four and eight years of follow-up, and we then created alluvial plots to visualise multimorbidity trajectories. We performed age- and sex-adjusted logistic regression analysis to study the association of each pattern with four- and eight-year mortality. We identified three multimorbidity patterns at baseline, named dyslipidaemia & endocrine-metabolic, hypertension & obesity, and unspecific. The hypertension & obesity pattern, found in one out of every four patients was associated with a higher likelihood of four- and eight-year mortality (age- and sex-adjusted odds ratio 1.11 and 1.16, respectively) compared to the unspecific pattern. Baseline patterns evolved into different patterns during the follow-up. Well-known preventable cardiovascular risk factors were key elements in most patterns, highlighting the role of hypertension and obesity as risk factors for higher mortality. Two out of every three patients had a cardiovascular profile with chronic conditions like diabetes and obesity that are linked to low-grade systemic chronic inflammation. More studies are encouraged to better characterise the relatively large portion of the population with an unspecific disease pattern and to help design and implement effective and comprehensive strategies towards healthier ageing.

Exploring the association between acute pancreatitis and biliary tract cancer: A large-scale population-based matched cohort study.

Biliary tract cancer (BTC) often goes undetected until its advanced stages, resulting in a poor prognosis. Given the anatomical closeness of the gallbladder and bile ducts to the pancreas, the inflammatory processes triggered by acute pancreatitis might increase the risk of BTC. To assess the association between acute pancreatitis and the risk of BTC. Using the Swedish Pancreatitis Cohort (SwePan), we compared the BTC risk in patients with a first-time episode of acute pancreatitis during 1990-2018 to a 1:10 matched pancreatitis-free control group. Multivariable Cox regression models, stratified by follow-up duration, were used to calculate hazard ratios (HRs), adjusting for socioeconomic factors, alcohol use, and comorbidities. BTC developed in 0.94% of 85,027 acute pancreatitis patients and in 0.23% of 814,993 controls. The BTC risk notably increased within 3months of hospital discharge (HR 82.63; 95% CI: 63.07-108.26) and remained elevated beyond 10years of follow-up (HR 1.82; 95% CI: 1.35-2.47). However, the long-term risk of BTC subtypes did not increase with anatomical proximity to the pancreas, with a null association for gallbladder and extrahepatic tumors. Importantly, patients with acute pancreatitis had a higher occurrence of early-stage BTC within 2years of hospital discharge than controls (13.0 vs. 3.6%; p-value <0.01). Our nationwide study found an elevated BTC risk in acute pancreatitis patients; however, the risk estimates for BTC subtypes were inconsistent, thereby questioning the causality of the association. Importantly, the amplified detection of early-stage BTC within 2years after a diagnosis of acute pancreatitis underscores the necessity for proactive BTC surveillance in these patients.

P1173 Higher total antioxidant capacity of diet is associated with reduced surgery risk in individuals with Inflammatory Bowel Disease in a prospective cohort study

Abstract Background Oxidative stress exacerbates inflammatory Bowel Disease (IBD), and dietary antioxidants are proposed as a promising manner to counteract this imbalance. However, the role of individual antioxidants in the complex milieu of the human body may exhibit synergistic or interactive effects. The research has yet to comprehensively examine the impact of dietary total antioxidant capacity (TAC) on IBD prognosis. To fill this knowledge gap, this study aimed to investigate the assocaitions between dietary TAC and risk of related surgery among individuals with IBD in a prospectively recruited cohort. Methods We included 2439 individuals with IBD at baseline from UK Biobank. All participants have completed a web-based validated 24-h dietary recall up to five rounds in 2009-2012, reporting their consumption of more than 200 foods and beverages. We calculated the TAC of the diet using the oxygen radical absorbance capacity method and were grouped by quintiles. The outcomes of interest were IBD-related surgery (bowel resection, perianal-related surgery, Strictureplasty, and ileoanal pouch formation), ascertained via linkage to national inpatient data. Cox proportional hazard models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results During a mean follow-up of 10.4 years, we identified 261 incident surgical cases related to IBD. The mean age of the participants was 56.9 years, and 51% were females. When comparing extreme quintiles of dietary TAC, individuals with higher dietary TAC were associated with a lower risk of related surgery (HR 0.57, 95% CI 0.38-0.86, P=0.007). The inverse associations between dietary TAC and related surgery were consistent among individuals with ulcerative colitis (HR comparing extreme quintiles 0.59, 95% CI 0.36-0.96, P=0.036). For individuals with Crohn’s disease, the associations were not significant when comparing extreme quintiles of dietary TAC (HR 0.51, 95% CI 0.25-1.03, P=0.060), while we observed a significant 9% risk reduction (HR 0.81, 95% CI 0.65-1.00, P=0.048) of related surgery by per 1-SD increment in dietary TAC among individuals with Crohn’s disease.(Table 1) Conclusion In this large large-scale population-based cohort study, we observed that higher dietary TAC was associated with reduced risk of related surgery in individuals with IBD. Our findings provide insights that could inform dietary recommendations and potentially improve IBD management strategies.

Do patients with cN0 oral squamous cell carcinoma benefit from elective neck dissection? A large-scale population-based study

BackgroundThe neck management of clinical-nodal negative (cN0) oral squamous cell carcinoma (OSCC) remains controversial. Elective neck dissection (END) and observation are the main strategies, but it is still not clear who could benefit the most from END. The purpose of this study was to clarify the potential clinical factors that affect the therapeutic value of END and to explore the actual characteristics associated with benefit from END.MethodsPatients with cN0 OSCC were identified in the SEER database from 2000 to 2019. 5-year Overall survival (OS) and disease-specific survival (DSS) were analyzed using the Kaplan‒Meier method, and the hazard ratios (HRs) for survival were estimated using the Cox regression model. Multiple subgroup analyses of DSS and OS among different factors, comparing END and No END, were performed.ResultsA total of 17,019 patients with cN0 OSCC were included. The basic survival analysis and Cox regression model showed that END increased the probability of 5-year DSS and OS and was an independent prognostic factor. However, among patients who underwent only primary tumor surgery, no significant differences were found between the END and No END groups in 5-year DSS (P = 0. 585) and OS (P = 0.465). Further subgroup analysis showed that primary sites and T stage, but not other factors, might influence the benefit of END. Significant differences were found for T1 (P < 0.001 for OS) and T2 (P = 0.001 for DSS and < 0.001 for OS) tongue squamous cell carcinoma (TSCC) but not for other primary tumor sites.ConclusionThis large-scale retrospective population-based cohort study suggests that not all patients with cN0 OSCC could benefit from END. Patients with cN0 TSCC are recommended to undergo END, especially with early-stage tumors.

Incidence of cardiovascular morbidity among Parkinson's disease patients; a large-scale cohort study in a 16-year time window around disease onset

ObjectivesTo examine the risk of any or specific types of cardiovascular diseases (CVDs) in patients with Parkinson's disease (PD), in the 16 years around disease onset, and to compare it to that in the general population. MethodsThis is a large-scale population-based retrospective cohort study of newly diagnosed PD patients, members of Maccabi Health Services (MHS), who started taking anti-parkinsonian drugs (APD) between 1/1/2000-31/12/2019 (study period). We collected information about CVD incidence (Congestive heart failure-CHF, Myocardial infarction-MI, Stroke) from MHS-CVD registry. We applied Cox regression to estimate adjusted-HR and 95%CI of CVD risks. We calculated Standardized-Incidence-Ratio (SIR) comparing CVD risks in the PD cohort to that of MHS population. ResultsThe PD cohort comprised 10,840 patients. During a mean follow up of 16.3 ± 4.3y around disease onset, 20.7% (n = 2241) were diagnosed with any CVD: 7.9% with CHF; 6.7% with MI, and 10.5% with stroke. Risks were higher for men: HR = 1.95 (95%CI 1.58–2.40), and for above age 75y at first APD treatment, HR = 2.00 (95% CI 1.65–2.43). Compared to the MHS population, the PD cohort exhibited a significantly lower risk for CVDs, especially for men: SIRmen = 0.21 (95%CI 0.20–0.22), SIRwomen = 0.29 (95% CI 0.27–0.31). These trends were similar for the specific CVDs. ConclusionsThe findings suggest that the risks that PD patients and particularly men, will develop any type of CVD are lower than those of the general population. Further studies are needed to confirm this finding and examine the underlying mechanisms.

Comparative cardiovascular outcomes in type 2 diabetes patients taking dapagliflozin versus empagliflozin: a nationwide population-based cohort study

BackgroundSodium-glucose co-transporter-2 inhibitors displayed cardiovascular benefits in type 2 diabetes mellitus in previous studies; however, there were some heterogeneities regarding respective cardiovascular outcomes within the class. Furthermore, their efficacies in Asians, females, and those with low cardiovascular risks were under-represented. Thus, we compared the cardiovascular outcomes between new users of dapagliflozin and empagliflozin in a broad range of patients with type 2 diabetes mellitus using a nationwide population-based real-world cohort from Korea.MethodsKorean National Health Insurance registry data between May 2016 and December 2018 were extracted, and an active-comparator new-user design was applied. The primary outcome was a composite of heart failure (HF)-related events (i.e., hospitalization for HF and HF-related death), myocardial infarction, ischemic stroke, and cardiovascular death. The secondary outcomes were individual components of the primary outcome.ResultsA total of 366,031 new users of dapagliflozin or empagliflozin were identified. After 1:1 nearest-neighbor propensity score matching, 72,752 individuals (mean age approximately 56 years, 42% women) from each group were included in the final analysis, with a follow-up of 150,000 ~ person-years. Approximately 40% of the patients included in the study had type 2 diabetes mellitus as their sole cardiovascular risk factor, with no other risk factors. The risk of the primary outcome was not different significantly between dapagliflozin and empagliflozin users (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.855–1.006). The risks of secondary outcomes were also similar, with the exception of the risks of HF-related events (HR 0.84, 95% CI 0.714–0.989) and cardiovascular death (HR 0.76, 95% CI 0.618–0.921), which were significantly lower in the dapagliflozin users.ConclusionsThis large-scale nationwide population-based real-world cohort study revealed no significant difference in composite cardiovascular outcomes between new users of dapagliflozin and empagliflozin. However, dapagliflozin might be associated with lower risks of hospitalization or death due to HF and cardiovascular death than empagliflozin in Asian patients with type 2 diabetes mellitus.

Incidence of Lyme Borreliosis in the Dutch General Practice Population: A Large-Scale Population-Based Cohort Study Across the Netherlands Between 2015 and 2019

Background: There is a need for updated incidence rates (IRs) of Lyme borreliosis (LB) in Europe, including the Netherlands. We estimated LB IRs stratified by geographic area, year, age, sex, immunocompromised status, and socioeconomic status (SES). Methods: All subjects registered in the PHARMO General Practitioner (GP) Database without prior diagnosis of LB or disseminated LB and having ≥1 year of continuous database enrolment were included. IRs and corresponding confidence intervals (CIs) of GP-recorded LB, erythema migrans (EM), and disseminated LB were estimated during the period 2015‒2019. Results: We identified 14,794 events (suspected, probable, or confirmed) with a diagnostic code for LB that included 8219 with a recorded clinical manifestation: 7985 (97%) with EM and 234 (3%) with disseminated LB. National annual LB IRs were relatively consistent, ranging from 111 (95% CI 106‒115) in 2019 to 131 (95% CI 126‒136) in 2018 per 100,000 person-years. Incidence of LB showed a bimodal age distribution, with peak IRs observed among subjects aged 5‒14 and 60‒69 years in men and women. Higher LB incidence was found in subjects who were residents of the provinces of Drenthe and Overijssel, immunocompromised, or of lower SES. Similar patterns were observed for EM and disseminated LB. Conclusions: Our findings confirm that LB incidence remains substantial throughout the Netherlands with no indication of decline in the past 5 years. Foci in two provinces and among vulnerable populations suggest potential initial target groups for preventive strategies such as vaccination.

Sugar intake and colorectal cancer risk: A prospective Japanese cohort study.

The influence of sugar consumption on the risk of colorectal cancer (CRC) remains controversial. Prospective cohort studies focusing on total and specific types of sugar intake among the Asian population who have different patterns of sugar intake sources than American and European populations are scarce. We intended to examine the association of sugar intake with CRC risk among middle-aged adults in a Japanese large-scale population-based cohort study. The participants (42,405 men and 48,600 women) who were 45-74 years old and answered the questionnaire in 1995-1999 in the Japan Public Health Center-based Prospective Study were followed up until December 2013. Total sugars, total fructose, and specific types of sugar intake were estimated using a validated 147-item food frequency questionnaire and divided into quintiles (Q1-Q5). We used Cox proportional hazard regression models adjusted for potential confounders to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During the follow-up, 2118 CRC cases (1226 men and 892 women) were identified. We did not observe any clear association between all types of sugar intake and an increased risk of CRC. Analyses by tumor sites yielded a positive association of total sugar consumption with rectal cancer in women (1.75 [1.07-2.87] for Q1 vs. Q5; p linear trend =0.03), but no statistically significant trend was detected among men. Sugar intake was not associated with CRC risk in middle-aged Japanese adults. However, for rectal cancer, the probability of an increased risk among women with a higher total sugar intake cannot be excluded.

Dietary behaviours and related lifestyles according to the presence or absence of skipping breakfast in Japanese adults: the JPHC-NEXT study.

To assess dietary behaviours and related lifestyles according to the presence or absence of skipping breakfast. We analysed the cross-sectional data from a baseline survey of a large-scale population-based cohort study in Japan conducted in 2011-2016. Participants provided information on dietary behaviours and lifestyles through a self-administered questionnaire. Skipping breakfast was defined as not eating breakfast at least once a week and was classified according to the frequency of skipping breakfast as 1-2, 3-4 or ≥5 times/week. Sixteen municipalities in seven prefectural areas across Japan under the Japan Public Health Centre-based prospective study for the Next Generation. 112 785 residents (51 952 males and 60 833 females) aged 40-74 years. After adjustment for age, socio-demographic status, drinking status and smoking status, individuals who skipped breakfast at least once a week, compared with those who ate breakfast every day, were more likely to have adverse dietary behaviours such as frequent eating out (multivariable OR = 2·08, 95 % CI (1·96, 2·21) in males and 2·15, 95 % CI (1·99, 2·33) in females), frequent eating instant foods (1·89, 95 % CI (1·77, 2·01) in males and 1·72, 95 % CI (1·56, 1·89) in females). They had late bedtime (1·85, 95 % CI (1·75, 1·95) in males and 1·98, 95 % CI (1·86, 2·11) in females) and living alone (2·37, 95 % CI (2·17, 2·58) in males and 2·02, 95 % CI (1·83, 2·21) in females), using the logistic regression model. Both adult males and females who skipped breakfast were likely to eat out, to have a dietary habit of eating instant foods and have lifestyles such as late bedtime and living alone than those who ate breakfast.

Effect of Lianhua Qingwen capsules on the positive rate of COVID-19 close contacts: A retrospective analysis of a large-scale population-based cohort study

ObjectiveCoronavirus disease 2019 (COVID-19) is still spreading worldwide. COVID-19 close contact is a key point of this epidemic. However, no medication is now available for close contact. This study aims to evaluate the beneficial effect and safety of the Lianhua Qingwen capsule (LHQW) on COVID-19 close contacts via a large, retrospective cohort study. MethodsA total of 25,002 close contacts from 199 quarantine sites in Changchun, Jilin, who underwent medical observation, were included. The information about these close contacts were collected for further epidemiological research. Moreover, subjects were divided into an exposure group (LHQW group, oral, 4 capsules/time, t.i.d.; 18,579 subjects) and a non-exposure group (control group; 6,423 subjects). Inverse probability of treatment weighting (IPTW) with propensity score was employed to evaluate the positive rate of the SARS-CoV-2 nucleic acid test in nasal and throat swabs confirmed by polymerase chain reaction (PCR). ResultsA total of 22,975 subjects were included in the analysis, 17,286 cases in the LHQW group and 5,689 cases in the control group. The positive rate of nucleic acid testing in the LHQW group was 5.12%, and that in the control group was 9.70% before the adjustment of IPTW of the propensity score; the difference between the two groups was -4.58% (95% CI -5.44- -3.77%, p < 0.001). After adjusting IPTW, the positive rate of nucleic acid testing in the LHQW group and the control group was 5.10% and 9.80%, respectively; the difference between the two groups was -4.70% (95% CI -5.18- -4.23, p < 0.001). The conclusions before and after the IPTW adjustment were consistent. No test drug-related adverse reactions were observed during the study period. ConclusionLHQW has a beneficial effect and safety on the close contacts of SARS-CoV-2 who are under medical observation at the quarantine sites and can be used as an optional drug for those close contacts.

Serum sex hormone-binding globulin is a mediator of the association between intrahepatic lipid content and type 2 diabetes: the Maastricht Study

Aims/hypothesisSerum sex hormone-binding globulin (SHBG) has been proposed to act as a hepatokine that contributes to the extrahepatic complications observed in non-alcoholic fatty liver disease (NAFLD). However, it remains uncertain whether serum SHBG mediates the association between intrahepatic lipids (IHL) and type 2 diabetes. Therefore, we studied whether, and to what extent, serum SHBG mediates the association between IHL content and type 2 diabetes.MethodsWe used cross-sectional data from the Maastricht Study (n=1554), a population-based cohort study with oversampling of individuals with type 2 diabetes. Type 2 diabetes status was assessed by oral glucose tolerance test, and IHL content was measured using 3T Dixon MRI. Mediation analyses were performed to assess the role of serum SHBG in mediating the association between IHL content and type 2 diabetes.ResultsIHL content was significantly associated with type 2 diabetes in women and men (OR 1.08 [95% CI 1.04, 1.14] and OR 1.12 [95% CI 1.08, 1.17], respectively). Serum SHBG significantly mediated the association between IHL content and type 2 diabetes. The contribution of serum SHBG was higher in women (OR 1.04 [95% CI 1.02, 1.07]; proportion mediated 50.9% [95% CI 26.7, 81.3]) than in men (OR 1.02 [95% CI 1.01, 1.03]; proportion mediated 17.2% [95% CI 9.6, 27.6]). Repeat analyses with proxies of type 2 diabetes and adjustment for covariates did not substantially affect the results.Conclusions/interpretationIn this large-scale population-based cohort study, serum SHBG was found to be a mediator of the association between IHL content and type 2 diabetes. These findings extend our understanding of the potential mechanisms by which NAFLD is a risk factor for type 2 diabetes, and further elaborate on the role of SHBG as a hepatokine.Graphical abstract

Association between Coffee Consumption and Risk of Prostate Cancer in Japanese Men: A Population-Based Cohort Study in Japan.

Although numerous epidemiological studies have examined whether coffee consumption is associated with prostate cancer risk, the results remain controversial. Moreover, there are few studies in Asian populations. Therefore, we investigated the association between coffee consumption and the risk of prostate cancer in a large-scale prospective population-based cohort study in Japan. Study subjects were 48,222 men (40-69 years) who completed a questionnaire that included questions about their coffee consumption in 1990 for Cohort I and 1993 for Cohort II and were followed up until December 31, 2015. Newly diagnosed cases were classified into localized and advanced using information on local staging, the Gleason score, and degree of differentiation. Hazard ratios (HR) and 95% confidential intervals (95% CI) were estimated using Cox regression analysis. A total of 1,617 participants were newly diagnosed with prostate cancer during a mean follow-up period of 18.8 years. Of these, 1,099 and 461 patients had localized and advanced cancer, respectively. There was no association between coffee intake and prostate cancer risk. Comparison between the highest and lowest category of coffee consumption produced HRs of 1.08 (95% CI, 0.90-1.30), 1.08 (95% CI, 0.84-1.38), and 1.00 (95% CI, 0.67-1.47) for risk of total, localized, and advanced cancer, respectively. The same results were obtained even when we limited the analysis to patients with subjective symptoms. Our findings suggest that coffee consumption has no impact on prostate cancer risk in Japanese men. Coffee has no protective effects against prostate cancer among Japanese men.