Population-based Longitudinal Cohort Study Research Articles

Health-care utilisation and associated economic burden in Major Depressive Disorder and Treatment-Resistant Depression in a longitudinal population-based cohort study of 110.000 patients

Major depressive disorder (MDD), and particularly treatment-resistant depression (TRD), lead to high levels of health-care use and disease burden. The aim of this study was to evaluate and compare the health-care resource utilisation and associated costs in these patient groups. It was a population-wide, retrospective analysis of NHS health-care electronic records in northwest London using the Discover-NOW platform, one of the largest interlinked datasets in Europe hosted by Imperial College Health Partners, which contains coded emergency and routine, primary and secondary, physical and mental health data, covering a population of more than 2.5 million. Eligible patients were adults with a diagnosis of MDD who had been prescribed at least one antidepressant between 2015 and 2020. A total of 110,406 patients were included, 101,333 [92%] with MDD and 9,073 [8%] with TRD. Mean duration of depression was 52.8 (SD 41.7) months for MDD and 70.8 (SD 37.8) months for TRD (p<0.0001). Patients with TRD had significantly higher risks of both psychiatric and somatic comorbidities such as anxiety, asthma, and alcohol misuse (all p<0.0001). They also demonstrated increased primary care and emergency attendance rates, more frequent and longer hospitalizations, and on average 1.5 times greater total healthcare costs compared to MDD patients. Primary care visits represented the largest proportion overall (TRD mean 162 [SD 96] vs. MDD 108 [90] visits per patient, p<0.0001; cost per patient £17,348 [SD £33,040] vs. £12,011 [£25,588], p<0.0001) during the study period. In secondary care, accident and emergency visits accounted for the highest use (TRD mean 5.5 [10.6] vs. MDD 3.54 [SD 6.0] visits per patient, p<0.0001) while non-elective hospitalisations incurred the highest costs (mean £2,518 [£8,064] vs. £1,909 [SD £6,807], p<0.0001). Demand increased with the duration of depression and the number of lines of treatment. The study highlights the substantial clinical and economic burden associated with MDD and especially TRD across different care settings.

Fertility and age at childbirth in Polycystic Ovary Syndrome: Results from a longitudinal population-based cohort study.

There are few studies in unselected populations describing reproductive outcomes in women with polycystic ovary syndrome (PCOS) at the end of their reproductive years. To compare parity and maternal age at deliveries and explore factors associated with advanced maternal age in a large, unselected population-based cohort, followed prospectively for 25 years. Women randomly selected from the general population and included in the prospective Australian Longitudinal Study on Women´s Health were assessed approximately every third year from 1996 (age 18 - 23 years) to 2021 (age 43 - 48 years). Women with and without self-reported PCOS diagnosis ((n=981 and n=13 266, respectively) were compared. Overall 9.9% of women reported having PCOS and by 43 - 48 years. Compared to women without PCOS, those with PCOS had fewer births (1.7 ± 1.3 vs. 1.9 ± 1.2, p<0.001), and more were nulliparous (23% vs. 18%, p=0.003). Women with PCOS were older at their first and second childbirths (29.5 ± 5.5 vs. 28.8 ± 5.5 years and 32.1 ± 5.2 vs. 31.1 ± 5.0 years, p<0.001 for both). PCOS was associated with increased odds of advanced maternal age at first childbirth, adjusted odds ratio (aOR) 1.40 (95% confidence interval 1.10-1.80), and increased odds of gestational diabetes, aOR 3.90 (2.99-5.10). However, type 2 diabetes and hypertension were not associated with advanced maternal age (aOR 0.81 (0.43-1.50) and aOR 0.78 (0.59-1.03), respectively. Within the PCOS group, a late PCOS diagnosis was associated with increased odds of advanced maternal age, aOR 1.98 (1.22-3.22). Women with PCOS have lower parity and give birth at a later age compared to women without PCOS. PCOS is associated with advanced maternal age, with subsequent increased pregnancy complications. Later PCOS diagnosis is associated with double the rate of advanced maternal age at birth, emphasizing the importance of timely diagnosis.

Trajectories of functional limitations, health-related quality of life and societal costs in individuals with long COVID: a population-based longitudinal cohort study

ObjectivesTo examine trajectories of functional limitations, fatigue, health-related quality of life (HRQL) and societal costs of patients referred to long COVID clinics.DesignA population-based longitudinal cohort study using real-time user data.Setting35...

Emotional and behavioral problems are associated with hypothalamic development from childhood to adolescence: Findings from a longitudinal cohort study

BackgroundDespite the pivotal role of the hypothalamus in regulating various physiological processes, our understanding of its developmental trajectory and subregional organization during childhood and adolescence remains limited, as well as how emotional and behavioral problems can impact hypothalamic development, potentially leading to neurodevelopmental disorders. MethodsThis population-based longitudinal cohort study utilized data from a representative sample of 702 children, who were followed two to five times. Emotional and behavioral problems were assessed using the Strengths and Difficulties Questionnaire (SDQ). Linear mixed models were employed to delineate developmental trajectories and behavioral regulation. ResultsUsing an automated segmentation technique, we quantified the volumes and asymmetries of the hypothalamus and its subregions in a large longitudinal sample of 702 subjects aged 6–15 years with 1371 MRI scans, and mapped their developmental trajectories. Our findings indicate that while the anterior and posterior regions of the hypothalamus exhibit a tendency toward decline, the tubular region demonstrates a linear increase which is influenced by lateralization, sex, and intracranial volume. Furthermore, emotional and behavioral problems - particularly emotional symptoms and peer relationship problems - are related to faster development in superior tubular and anterior-superior regions. ConclusionsIn this study, we initially delineated the developmental trajectories of the hypothalamus and its subregions from childhood to adolescence based on a longitudinal cohort study. Our findings revealed that the development of hypothalamus followed the pattern of “lateral early to medial late, and dorsomedial early to ventromedial late”, and the emotional and behavioral problems are associated with faster hypothalamic development. This study provides preliminary evidence regarding the impact of emotional and behavioral problems on the dynamic development of the hypothalamus, offering a crucial foundation for future prevention and intervention strategies targeting cognitive and emotional behavioral problems.

Association of childhood obesity or weight change with early-onset follicular occlusion triad among children.

The effects of childhood obesity or weight gain on the development of early-onset follicular occlusion triad (FOT) among children, which includes hidradenitis suppurativa (HS), acne conglobata (AC), and dissecting cellulitis of the scalp (DCS), remain unknown. To investigate the association between body mass index (BMI) or its changes and early-onset FOT development. This nationwide population-based longitudinal cohort study included a cohort of 2,012,928 Korean children who underwent two consecutive health examinations at 30-36 months and 42-48 months of age between 2009 and 2020. The BMI and its changes derived during health screenings at 30-36 and 42-48 months. We performed multivariate Cox proportional hazards regression analyses to estimate the risk of early-onset FOT, including HS, AC, and DCS. During the follow-up, 1,283 FOT, including 143 HS, 1,068 AC, and 72 DCS, events were identified. Children with obesity were at an elevated risk of early-onset FOT compared to those with a normal weight (FOT: adjusted hazard ratio [aHR] 1.49, 95% confidence interval [CI] 1.21-1.84; HS: aHR 2.30, 95% CI 1.39-3.82; AC: aHR 1.36, 95% CI 1.07-1.73). BMI gain was correlated with an elevated risk of early-onset FOT, particularly HS, whereas BMI loss was linked to a decreased risk of early-onset FOT, especially HS. Children who became obese had an increased early-onset FOT risk (aHR 1.51, 95% CI 1.07-2.14) compared to those who maintained a normal weight. Children who reduced from obese to normal weight exhibited a decreased risk of early-onset FOT (FOT: aHR 0.41, 95% CI 0.17-0.96, P for trend=0.02; HS: P for trend=0.05) compared to obese children who retained their weight. Childhood obesity was associated with an elevated risk of early-onset FOT, including HS and AC. Weight gain was correlated with an increased risk of early-onset FOT, especially HS, while weight loss was associated with a decreased risk of early-onset FOT, particularly HS. Implementing purposeful weight-reduction strategies may be helpful in preventing early-onset FOT development.

Hidradenitis Suppurativa and Maternal and Offspring Outcomes

Hidradenitis suppurativa (HS) is associated with morbidity in persons of reproductive age, but the effect on maternal and offspring outcomes is understudied. To determine the association of HS with pregnancy outcomes and maternal and child morbidity in the long term. This population-based longitudinal cohort study with up to 16 years of follow-up took place between 2006 and 2022 in Quebec, Canada. . Maternal HS. Outcomes included hypertensive disorders of pregnancy, gestational diabetes, and other birth outcomes as well as the long-term risk of hospitalization up to 16 years after delivery. The study used adjusted log-binomial and Cox proportional hazards regression models to estimate the association between maternal HS and pregnancy outcomes or hospitalization following pregnancy. Outcomes in both mothers and offspring were assessed. There were 1 324 488 deliveries during the study, including 1332 (0.1%) among mothers with HS. Compared with patients without HS, patients with HS had a greater risk of hypertensive disorders of pregnancy (risk ratio [RR], 1.55 [95% CI, 1.29-1.87]), gestational diabetes (RR, 1.61 [95% CI, 1.40-1.85]), and severe maternal morbidity (RR, 1.38 [95% CI, 1.03-1.84]). In neonates, maternal HS was associated with risk of preterm birth (RR, 1.28 [95% CI, 1.07-1.53]) and birth defects (RR, 1.29 [95% CI, 1.07-1.56]). In the long term, HS was associated with 2.29 times the risk of maternal hospitalization (95% CI, 2.07-2.55) and 1.31 times the risk of childhood hospitalization (95% CI, 1.18-1.45), including hospitalization for respiratory, metabolic, psychiatric, and immune-related morbidity over time. This cohort study found that HS is associated with adverse maternal and offspring outcomes in the peripartum period and in the long term. Early detection and management of HS may help mitigate these outcomes.

6893 The Interaction Effect Between BMI, Diabetes, and Age at Diabetes Onset on the Risk of Thyroid Cancer: A Population-Based Cohort Study

Abstract Disclosure: T. Hou: None. Y. Li: None. J. Tian: None. Z. Bloomgarden: None. Y. Shi: None. ObjectiveThe relationship between type 2 diabetes mellitus (T2DM) and thyroid cancer was confounded by some characteristics of diabetes. We aimed to determine the association of the presence of diabetes and, among persons with diabetes, the age at T2DM onset, BMI, and the interactive effect with the subsequent thyroid cancer risk. MethodsWe conducted a population-based longitudinal cohort study including 428,568 persons with new-onset T2DM matched with the general population (100,649,346 person-years). Risk of thyroid cancer by subgroups were calculated based on standardized incidence ratio (SIR), hazard ratio (HR), and Cox proportional hazards models. ResultsIn T2DM patients, 1142 thyroid cancer cases were identified during eight years of follow-up, with an incidence rate of 59.01/100,000 person-years and a higher SIR: 1.21 (95% CI: 1.14-1.28) compared to the general population. New-onset T2DM had an overall 21% higher risk of thyroid cancer. Both the earlier age at T2DM onset and higher BMI were associated with a significant increasing risk of thyroid cancer independently (T2DM onset age &amp;lt;50: SIR 1.46 (1.27-1.69); BMI ≥30.0 Kg/m2 SIR: 1.93 (1.57-2.38)). The highest risk of cancer appeared in the patients with both BMI ≥30.0 Kg/m2 and T2DM onset age &amp;lt;50 years (SIR=3.91, HR=3.04). Among patients with T2DM onset age &amp;lt;60 years, SIR shows an increasing trend of cancer risk with higher BMI levels, while no significant increasing trends with higher BMI in T2DM onset age ≥60 years. For patients with BMI ≥25.0 Kg/m2, SIR of cancer risk decreases with an later T2DM onset age, whereas no significant decreasing trends of cancer risk in BMI &amp;lt;24.9 Kg/m2 group. Obese (BMI ≥30.0 Kg/m2) patients had a significant higher HR of thyroid cancer only when T2DM onset age &amp;lt;60 years. ConclusionsBoth earlier age of T2DM onset (&amp;lt;50 years) and higher BMI (≥30 Kg/m2) contributed to higher risk of thyroid cancer. These results suggest that earlier screening of thyroid cancer might be appropriate in patients diagnosed with T2DM, especially in individuals with young-onset T2DM and obesity. Presentation: 6/3/2024

Adverse outcomes after surgery after a cerebrovascular accident or acute coronary syndrome: a retrospective observational cohort study

BackgroundDelaying surgery after a major cardiovascular event might reduce adverse postoperative outcomes. The time interval represents a potentially modifiable risk factor but is not well studied. MethodsThis was a longitudinal retrospective population-based cohort study, linking data from Hospital Episode Statistics for NHS England and the Myocardial Ischaemia National Audit Project. Adults undergoing noncardiac, non-neurologic surgery in 2007–2018 were included. The time interval between a preoperative cardiovascular event and surgery was the main exposure. The outcomes of interest were acute coronary syndrome (ACS), acute myocardial infarction (AMI), cerebrovascular accident (CVA) within 1 year of surgery, unplanned readmission (at 30 days and 1 year), and prolonged length of stay. Multivariable logistic regression models with restricted cubic splines were used to estimate adjusted odds ratios (aORs; age, sex, socioeconomic deprivation, and comorbidities). ResultsIn total, 877 430 people had a previous cardiovascular event and 20 582 717 were without an event. CVA, ACS, and AMI in the year after elective surgery were more frequent after prior cardiovascular events (adjusted hazard ratio 2.12, 95% confidence interval [CI] 2.08–2.16). Prolonged hospital stay (aOR 1.36, 95% CI 1.35–1.38) and 30-day (aOR 1.28, 95% CI 1.25–1.30) and 1-yr (aOR 1.60, 95% CI 1.58–1.62) unplanned readmission were more common after major operations in those with a prior cardiovascular event. After adjusting for the time interval between preoperative events until surgery, elective operations within 37 months were associated with an increased risk of postoperative ACS or AMI. The risk of postoperative stroke plateaued after a 20-month interval until surgery, irrespective of surgical urgency. ConclusionsThese observational data suggest increased adverse outcomes after a recent cardiovascular event can occur for up to 37 months after a major cardiovascular event.

Clinically validated HPV assays offer comparable long-term safety in primary cervical cancer screening: A 9-year follow-up of a population-based screening cohort.

Molecular testing for human papillomaviruses (HPV) is gradually replacing cytology in cervical cancer screening. In this longitudinal population-based cohort study, 4140 women 20 to 64 years old attending organized screening were tested at baseline by five different screening methods and followed for 9 years. To assess long-term safety, the cumulative risks of CIN2+/CIN3+ were estimated after a negative baseline result obtained by conventional cytology and four clinically validated HPV assays: Hybrid Capture 2 (hc2), RealTime High Risk HPV assay (RealTime), cobas 4800 HPV Test (cobas_4800), and Alinity m HR HPV (Alinity). HPV-negative women at baseline had a substantially lower risk for CIN2+ compared to those with normal baseline cytology: 0.84% (95% CI, 0.46-1.22), 0.90% (95% CI, 0.51-1.29), 0.78% (95% CI, 0.42-1.15), and 0.75% (95% CI, 0.39-1.11) for hc2, RealTime, cobas_4800, and Alinity, respectively, compared to 2.46% (95% CI, 1.88-3.03) for cytology. No differences were observed between HPV assays in longitudinal sensitivity (range: 86.21%-90.36%) and negative predictive values (range: 99.54%-99.70%) for CIN2+ in women ≥30 years, but were significantly different from cytology (p < .05). The 9-year cumulative risk of CIN2+ differed significantly between HPV genotypes, reaching 32.1% (95% CI, 14.5-46.1) for HPV16, 24.9% (95% CI, 4.7-40.8) for HPV18/45, 27.2% (95% CI, 14.6-37.8) for HPV31/33/35/52/58, and 8.1% (95% CI, 0.0-16.7) for HPV39/51/56/59. Four clinically validated HPV assays showed comparable safety and better assurance against precancerous lesions than cytology, but some important differences were identified in the performance characteristics of HPV assays impacting the referral rate. Information about the HPV genotype is valuable for guiding further clinical action in HPV-based screening programs.

Increase in short-term and long-term stress-associated mental illness after Jiji earthquake in Taiwan: A twenty-year longitudinal population-based cohort study (1999–2019)

BackgroundEarthquakes have caused profound physical and mental health impacts in human history. The Jiji earthquake, which had a magnitude of 7.6 on the Richter scale, occurred on 21 September 1999 in Taiwan. A close follow-up on the mental health status of affected adults after major natural disasters to construct the short-term and long-term risk and prevalence of stress-associated mental illnesses has not been performed by using the nationwide health databases. MethodsThis population-based cohort study included 468,804 adults affected by Jiji earthquake spanning from 2000 to 2019 who were matched at a 1:4 ratio with unaffected individuals based on age and sex (n = 1,875,216). Employing a subdistribution hazard regression analysis, we assessed the incidence of sleep, anxiety, and depressive disorders after Jiji earthquake. Corrections for multiple comparisons were carried out using the Benjamini–Hochberg procedure. ResultsAffected adults experienced an increased incidence of short-term (approximately twice) stress-associated psychiatric disorders. The risk of the post-traumatic stress disorder (PTSD) is significantly higher in the affected adults (40–64 years: aSHR: 92.0; ≥65 years: aSHR: 96.7, p < 0.0001). Middle-aged (aged 40–64 years) male adults presented with significantly more short-term (< one year) and long-term (up to 20 years) stress-related mental illnesses, i.e., insomnia, anxiety, and depressive disorders, than individuals in the control group. ConclusionsAn earthquake has significant short and long-term effects on sleep quality, anxiety, and depressive disorders in affected adults. Optimal short and long-term close monitoring is needed to deploy medical resources and socioeconomic support to relieve mental stress burdens.

4. The impact of cannabis on opioid use and postoperative complications in cervical fusion: a population-based longitudinal cohort study

4. The impact of cannabis on opioid use and postoperative complications in cervical fusion: a population-based longitudinal cohort study

Branched-Chain Amino Acids, Alanine, and Thyroid Function: A Cross-Sectional, Nuclear Magnetic Resonance (NMR)-Based Approach from ELSA-Brasil.

The association of thyroid function with essential and non-essential amino acids is understudied, despite their common metabolic roles. Thus, our aim was to evaluate the association of thyroid function with the levels of branched-chain amino acids (BCAAs-leucine, isoleucine, and valine) and of alanine in the general population. We utilized data from the São Paulo research center of ELSA-Brasil, a longitudinal population-based cohort study. Thyroid parameters included thyroid stimulating hormone (TSH), free T4 and free T3 levels, and the FT4:FT3 ratio. BCAAs and alanine were analyzed on a fully automated NMR platform. The current analysis included euthyroid participants and participants with subclinical hyperthyroidism and hypothyroidism. We used Pearson's coefficient to quantify the correlation between thyroid-related parameters and amino acids. Linear regression models were performed to analyze whether thyroid parameters were associated with BCAAs and alanine levels. We included 4098 participants (51.3 ± 9.0 years old, 51.5% women) in this study. In the most adjusted model, higher levels of TSH were associated with higher levels of alanine, FT4 levels were inversely associated with isoleucine levels, FT3 levels were statistically significant and positively associated with valine and leucine, and the T3:T4 ratio was positively associated with all amino acids. We observed that subclinical hypothyroidism was positively associated with isoleucine and alanine levels in all models, even after full adjustment. Our findings highlight the association of subclinical hypothyroidism and thyroid-related parameters (including TSH, free T4, free T3, and FT4:FT3 ratio) with BCAAs and alanine. Further studies are needed to explore the mechanisms underlying this association. These insights contribute to our understanding of the influence of thyroid-related parameters on BCAA and alanine metabolism.

The HIV Care Cascade for Older Adults in Rural South Africa: A Longitudinal Cohort Study (2014-2019).

As people with HIV grow older, stable engagement in care is essential for healthy aging. We evaluate the HIV care cascade for older adults in rural South Africa at 2 time points cross-sectionally and assess movement in the cascade over time. We evaluated the cascade stage at waves 1 (2014-2015) and 2 (2018-2019) of Health and Aging in Africa: A Longitudinal Study of an INDPETH Community in South Africa, a population-based longitudinal cohort study in Mpumalanga Province, South Africa. Biomarker screening defined cascade stages [HIV+/no antiretroviral therapy (ART); ART+/unsuppressed viral load; ART+/suppressed viral load]. Between-wave probability of death, cascade progression, regression, cascade transitions, and sociodemographic predictors were assessed with Poisson regression. The impact of death was considered using the Fine and Gray competing risk model. We observed a higher prevalence of antiretroviral therapy with viral suppression over time (50% in wave 1 vs. 70% in wave 2). Among those alive, the oldest age group (70+ years old) was most likely to have cascade progression [adjusted risk ratio for treatment initiation vs. 40-49 years old: 1.38 (95% confidence interval: 1.02 to 1.86)]. However, there was a significant risk of death and cascade regression. Death between waves reached 40% for 70+-year-olds who were ART+/unsuppressed. In competing risk models, older age was associated with equivalent or less cascade progression. Older age groups who were unsuppressed on treatment and men had poorer cascade outcomes. Improvements observed in HIV treatment coverage over time for older adults must be interpreted in the context of the high risk of death for older HIV-positive adults, especially among those failing treatment.

Investigating the Differential Impact of Short- and Long-Term Informal Caregiving on Mental Health Across Adolescence: Data From the Tokyo Teen Cohort

PurposeYoung caregivers experience, on average, poorer mental health outcomes than non–caregiving young people. However, it is unknown to what extent these effects differ with age, or among short-term versus long-term caregivers. Using repeated assessment of young caregiving across multiple waves of a prospective adolescent cohort study, we conducted repeated cross-sectional analyses of caregiver status and contemporaneous depressive symptoms, self-harm, and suicidality in early to middle adolescence. MethodsFour waves of questionnaire data from a large, longitudinal population-based cohort study (Tokyo Teen Cohort) were analyzed. Caregiver status was collected from participants aged 10, 12, 14, and 16 years. Mental health outcomes assessed were depressive symptoms, self-harm and suicidal feelings. Logistic regression analyses were conducted assessing effects of a) young caregiver status and b) new, long-term, and ex-caregiver 2-year categorizations on mental health outcomes at 12, 14, and 16 years, both unadjusted and adjusted for potential confounders (sex, low income, single-parent household, and parental distress). ResultsDepressive symptoms were elevated among long-term caregivers at 14 years (unadjusted odds ratio (uOR): 3.11 [1.33–7.27], adjusted odds ratio (aOR): 2.49 [1.03–5.99]). Borderline associations between long-term caregiving and self-harm (uOR: 3.14 [1.06–9.35], aOR: 2.51 [0.82–7.63]) and suicidal feelings (uOR: 2.49 [0.98–6.34], aOR: 2.06 [0.80–5.33]) were detected at 16 years. No associations were found at age 12 years in primary analyses; sensitivity analyses indicated possible increased depressive symptoms. DiscussionYoung caregivers with long-term caregiving roles are at the greatest risk for negative mental health outcomes, with effects concentrated in later adolescence. These findings highlight urgent need for early identification and practical and psychological support for young people shouldering caregiving burdens.

P-688 Fertility and age at childbirth in polycystic ovary syndrome: results from a longitudinal population-based cohort study

Abstract Study question How does fertility differ between women with and without polycystic ovary syndrome (PCOS), and which factors are associated with advanced maternal age? Summary answer Women with PCOS have less births. PCOS was associated with advanced maternal age, with later diagnosis associated with double the rate of advanced maternal age. What is known already PCOS affects 12% or 140 million women globally. Women with PCOS have broad features including ovulatory disturbances and increased infertility; however, few studies have explored reproductive outcomes in PCOS at the end of reproductive age. In the general population advanced maternal age, defined as giving birth after age 35 years, is associated with increased risk of pregnancy complications and reduced fertility. A recent register-based study found increased risk of advanced maternal age in women with PCOS, yet PCOS prevalence was underreported, and the study did not adjust for important confounders. Study design, size, duration Prospective cohort study. Women with (n = 981) and without (n = 13 266) self-reported PCOS diagnosis were compared during a 25-year follow-up. Participants/materials, setting, methods Women randomly selected from the general population and included in the prospective Australian Longitudinal Study on Women’s Health were assessed with surveys every third year from 1996 (age 18-23 years) to 2021 (age 43-48 years). Main results and the role of chance Overall 9.9% of women reported having PCOS and by 43-48 years, those with PCOS had less births (1.7 ±1.3 vs. 1.9 ±1.2, p &amp;lt; 0.001), and more were nulliparous, 23% vs. 18%, p = 0.003. They were older than women without PCOS at their first, and second childbirth (29.5 ±5.49 vs. 28.8 ±5.48 years and 32.1 ±5.16 vs. 31.1 ±5.00 years, p &amp;lt; 0.001 for both). PCOS was associated with increased odds of advanced maternal age at first childbirth, adjusted odds ratio (aOR) 1.34 (95% confidence interval 1.04-1.75), whereas type 2 diabetes (aOR 0.68 (0.61-1.10)) or hypertension (aOR 0.82 (0.61-1.10)) were not associated with advanced maternal age. Within the PCOS group, a late PCOS diagnosis was associated with increased odds of advanced maternal age, aOR 2.05 (1.24-3.40). Limitations, reasons for caution All outcomes were self-reported. Wider implications of the findings Women with PCOS have lower parity. Later diagnosis is associated with increased odds of advanced maternal age at first childbirth. Given poor reproductive outcomes with increased maternal age, we highlight the importance of earlier diagnosis, patient education and implementation of a reproductive life-plan to optimize attainment of aspirational family size. Trial registration number not applicable

Familial Loss of a Loved One and Biological Aging

The link between familial loss of a loved one and long-term health decline is complex and not fully understood. To test associations of losing a parent, sibling, child, or partner or spouse with accelerated biological aging. Data from the National Longitudinal Study of Adolescent to Adult Health, a US population-based longitudinal cohort study, were analyzed. Participants were enrolled from 1994 to 1995 for wave 1, while in grades 7 to 12, and followed up through wave 5 in 2018. The study analyzed participant reports of loss collected at each wave from 1 to 5 over 24 years and used a banked wave 5 blood sample for subsequent DNA methylation testing and epigenetic clock calculation from 2018 to 2024. Data were analyzed from January 2022 to July 2024. Loss of biological parents or parental figures, partners or spouses, siblings, or children at waves 1 to 3 or during childhood, adolescence (aged <18 years), or adulthood at wave 4 to wave 5 (aged 18-43 years). Biological aging assessed from blood DNA methylation using the Horvath, PhenoAge, GrimAge, and DunedinPACE epigenetic clocks at wave 5. Data from 3963 participants were analyzed, with a weighted mean (range) age of 38.36 (36.78-39.78) years at wave 5; 2370 (50.3%) were male, 720 (15.97%) were Black, 400 (8.18%) were Hispanic, and 2642 (72.53%) were White. Nearly 40% of participants experienced loss by wave 5 when they were aged 33 to 43 years, and participants who were Black (379 participants [56.67%]), Hispanic (152 participants [41.38%]), and American Indian (18 participants [56.08%]) experienced a greater proportion of losses compared with White participants (884 participants [34.09%]). Those who experienced 2 or more losses tended to have older biological ages for several of the clocks (PhenoAge β = 0.15; 95% CI, 0.02 to 0.28; GrimAge β = 0.27; 95% CI, 0.09 to 0.45; DunedinPACE β = 0.22; 95% CI, 0.10 to 0.34) compared with those with no losses. In contrast, there were no associations with 2 or more losses for the Horvath clock (β = -0.08; 95% CI, -0.23 to 0.06). This study reveals associations between various measures of loss experienced from childhood to adulthood and biological aging in a diverse sample of the US population. These findings underscore the potentially enduring impact of loss on biological aging even before middle age and may contribute to understanding racial and ethnic disparities in health and mortality.

Outcomes of Bypass Surgery in Adult Moyamoya Disease by Onset Type

Moyamoya disease (MMD) is a rare chronic cerebrovascular disease, and the outcomes of bypass management in adult patients remain controversial. To categorize adult MMD based on asymptomatic, ischemic, and hemorrhagic onset and compare the outcomes (death, hemorrhagic stroke [HS], and ischemic stroke [IS]) of bypass surgery (direct or indirect) with those of conservative management. This retrospective, nationwide, population-based longitudinal cohort study used Korean National Health Insurance Research data to identify adults (aged ≥15 years) with MMD who were diagnosed between January 1, 2008, and December 31, 2020, and followed up until December 31, 2021 (median follow-up, 5.74 [IQR, 2.95-9.42] years). A total of 19 700 participants (3194 with hemorrhagic, 517 with ischemic, and 15 989 with asymptomatic MMD) were included. Data were analyzed from January 2 to April 1, 2023. Bypass surgery and conservative management. Death constituted the primary outcome; secondary outcomes consisted of HS or IS. Kaplan-Meier survival curve and Cox proportional hazards regression analysis were applied. The propensity score-matching and stratified analyses were performed to control covariate effects. A total of 19 700 patients (mean [SD] age, 45.43 [14.98] years; 12 766 [64.8%] female) were included. Compared with conservative management, bypass was associated with a reduced risk of death (adjusted hazard ratio [AHR], 0.50 [95% CI, 0.41-0.61]; P < .001) and HS (AHR, 0.36 [0.30-0.40]; P < .001) in hemorrhagic MMD; reduced risk of IS (AHR, 0.55 [95% CI, 0.37-0.81]; P = .002) in ischemic MMD; and reduced risk of death (AHR, 0.74 [95% CI, 0.66-0.84]; P < .001) in asymptomatic MMD. However, bypass was associated with an increased risk of HS (AHR, 1.76 [95% CI, 1.56-2.00]; P < .001) in asymptomatic MMD. Both direct and indirect bypass demonstrated similar effects in hemorrhagic and asymptomatic MMD, except only direct bypass was associated with a reduced risk of IS (AHR, 0.52 [95% CI, 0.33- 0.83]; P = .01) in ischemic MMD. After stratification, bypass was associated with a reduced risk of death in patients younger than 55 years with ischemic (AHR, 0.34 [95% CI, 0.13- 0.88]; P = .03) and asymptomatic (AHR, 0.69 [95% CI, 0.60-0.79]; P < .001) MMD, but an increased risk of HS in patients 55 years or older with ischemic MMD (AHR, 2.13 [95% CI, 1.1-4.16]; P = .03). The findings of this cohort study of bypass outcomes for patients with MMD emphasize the importance of tailoring management strategies in adult patients based on onset types.

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.

A critique and examination of the polysocial risk score approach: predicting cognition in the Health and Retirement Study.

Polysocial risk scores were recently proposed as a strategy for improving the clinical relevance of knowledge about social determinants of health. Our objective in this study was to assess whether the polysocial risk score model improves prediction of cognition and all-cause mortality in middle-aged and older adults beyond simpler models including a smaller set of key social determinants of health. We used a sample of 13 773 individuals aged ≥50 years at baseline from the 2006-2018 waves of the Health and Retirement Study, a US population-based longitudinal cohort study. Four linear mixed models were compared: 2 simple models including a priori-selected covariates and 2 polysocial risk score models which used least absolute shrinkage and selection operator (LASSO) regularization to select covariates among 9 or 21 candidate social predictors. All models included age. Predictive accuracy was assessed via R2 and root mean-squared prediction error (RMSPE) using training/test split validation and cross-validation. For predicting cognition, the simple model including age, race, sex, and education had an R2 value of 0.31 and an RMSPE of 0.880. Compared with this, the most complex polysocial risk score selected 12 predictors (R2=0.35 and RMSPE=0.858; 2.2% improvement). For all-cause mortality, the simple model including age, race, sex, and education had an area under the receiver operating characteristic curve (AUROC) of 0.747, while the most complex polysocial risk score did not demonstrate improved performance (AUROC=0.745). Models built on a smaller set of key social determinants performed comparably to models built on a more complex set of social "risk factors."

Impact of aging on acute myeloid leukemia epidemiology and survival outcomes: A real-world, population-based longitudinal cohort study.

Acute myeloid leukemia (AML) is a severe and fatal form of leukemia that is prevalent in the older population. In this longitudinal retrospective study, we investigated the epidemiology and survival rates of patients diagnosed with de novo acute myeloid leukemia in South Korea from Jan 1, 2011, to Aug 31, 2020. We used real-world data from the Health Insurance Review and Assessment Service database. We observed an increase in the number of acute myeloid leukemia cases, with age-specific incidence rates escalating in older patients. In contrast a long-term decrease from 1.94 to 1.77 per 100,000 individuals was found in the age-standardized incidence rates. Meanwhile, age-standardized prevalence rates ascended from 8.93 to 9.67 per 100,000 individuals, with a remarkable increase in the age-specific prevalence rate for those aged 80 years and above. Survival rates were notably better in younger or treated patients, and in those who underwent Hematopoietic stem cell transplantation. The time of diagnosis did not affect the survival of patients younger than 65 years. However, the most recent survival rates were significantly lower for patients 65 or older, as shown in the unadjusted Cox survival analysis. After adjustments in the analysis, it was found that the overall survival rates of the most recently diagnosed group improved significantly compared with those diagnosed earlier, with a hazard ratio of 0.90 (95% confidence interval, 0.84-0.97). This improvement may potentially be influenced by the enhanced treatment alternatives available for newly diagnosed older patients aged 65 years or older. In conclusion, aging appears to fuel an increase in the number of acute myeloid leukemia cases and mortality. Further studies are warranted to understand the impact of aging on acute myeloid leukemia treatment outcomes and devise efficacious care strategies for older patients.