Cohort Inception Research Articles

Progression of frailty and cardiovascular outcomes among Medicare beneficiaries.

Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent influence of frailty progression on cardiovascular outcomes remains uncertain. To determine whether frailty progression is associated with adverse cardiovascular outcomes, independent of baseline frailty and age, we evaluated all Medicare Fee-for-Service beneficiaries ≥65 years at cohort inception with continuous enrollment from 2003 to 2015. Linear mixed effects models, adjusted for baseline frailty and age, were used to estimate change in a validated claims-based frailty index (CFI) over a 5-year period. Survival analysis was used to examine frailty progression and risk of adverse health outcomes. There were 8.9 million unique patients identified, mean age 77.3 ± 7.2 years, 58.7% female, 10.9% non-White race. In total, 60% had frailty progression and 40% frailty regression over median follow-up of 2.4 years. Compared to those with frailty regression, when adjusting for age and baseline CFI, those with frailty progression had a significantly greater risk of incident major adverse cardiovascular and cerebrovascular events (MACCE) (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.31-1.31), all-cause mortality (HR 1.34, 95% CI 1.34-1.34), acute myocardial infarction (HR 1.08, 95% CI 1.07-1.09), heart failure exacerbation (HR 1.30, 95% CI 1.29-1.30), ischemic stroke (HR 1.14, 95% CI 1.14-1.15). There was also a graded increase in risk of each outcome with more rapid progression, as well as significantly fewer days alive at home (DAH) with more rapid progression compared to the slowest progression group (270.4 ± 112.3 vs. 308.6 ± 93.0 days, rate ratio 0.88, 95% CI 0.87-0.88, p < 0.001). In this large, nationwide sample of older Medicare beneficiaries, frailty progression, independent of age and baseline frailty, was associated with fewer DAH and a graded risk of MACCE, all-cause mortality, myocardial infarction, heart failure, and ischemic stroke compared to those with frailty regression.

Decision making for health-related research outcomes that alter diagnosis: A model from paediatric brain tumours.

The question of how to handle clinically actionable outcomes from retrospective research studies is poorly explored. In neuropathology, this problem is exacerbated by ongoing refinement in tumour classification. We sought to establish a disclosure threshold for potential revised diagnoses as determined by the neuro-oncology speciality. As part of a previous research study, the diagnoses of 73 archival paediatric brain tumour samples were reclassified according to the WHO 2016 guidelines. To determine the disclosure threshold and clinical actionability of pathology-related findings, we conducted a result-evaluation approach within the ethical framework of BRAIN UK using a surrogate clinical multidisciplinary team (MDT) of neuro-oncology specialists. The MDT identified key determinants impacting decision-making, including anticipated changes to patient management, time elapsed since initial diagnosis, likelihood of the patient being alive and absence of additional samples since cohort inception. Ultimately, none of our research findings were considered clinically actionable, largely due to the cohort's historic archival and high-risk nature. From this experience, we developed a decision-making framework to determine if research findings indicating a change in diagnosis require reporting to the relevant clinical teams. Ethical issues relating to the use of archival tissue for research and the potential to identify actionable findings must be carefully considered. We have established a structured framework to assess the actionability of research data relating to patient diagnosis. While our specific findings are most applicable to the pathology of poor prognostic brain tumour groups in children, the model can be adapted to a range of disease settings, for example, other diseases where research is dependent on retrospective tissue cohorts, and research findings may have implications for patients and families, such as other tumour types, epilepsy-related pathology, genetic disorders and degenerative diseases.

Incident Diabetes in Women With Patterns of Gestational Diabetes Occurrences Across 2 Pregnancies

Gestational diabetes is a type 2 diabetes risk indicator, and recurrence further augments risk. In women with a single occurrence across 2 pregnancies, it is unclear whether first- vs second-pregnancy gestational diabetes differ in terms of risk. To compare the hazards of incident diabetes among those with gestational diabetes in the first, in the second, and in both pregnancies with women without gestational diabetes in either. This was a retrospective cohort study with cohort inception from April 1, 1990, to December 31, 2012. Follow-up was April 1, 1990, to April 1, 2019. Participants were mothers with 2 singleton deliveries between April 1, 1990, and December 31, 2012, without diabetes before or between pregnancies, who were listed in public health care insurance administrative databases and birth, stillbirth, and death registries in Quebec, Canada. Data were analyzed from July to December 2023. Gestational diabetes occurrence(s) across 2 pregnancies. Incident diabetes from the second delivery until a third pregnancy, death, or the end of the follow-up period, whichever occurred first. The 431 980 women with 2 singleton deliveries studied had a mean (SD) age of 30.1 (4.5) years at second delivery, with a mean (SD) of 2.8 (1.5) years elapsed between deliveries; 373 415 (86.4%) were of European background, and 78 770 (18.2%) were at the highest quintile of material deprivation. Overall, 10 920 women (2.5%) had gestational diabetes in their first pregnancy, 16 145 (3.7%) in their second, and 8255 (1.9%) in both (12 205 incident diabetes events; median [IQR] follow-up 11.5 [5.3-19.4] years). First pregnancy-only gestational diabetes increased hazards 4.35-fold (95% CI, 4.06-4.67), second pregnancy-only increased hazards 7.68-fold (95% CI, 7.31-8.07), and gestational diabetes in both pregnancies increased hazards 15.8-fold (95% CI, 15.0-16.6). Compared with first pregnancy-only gestational diabetes, second pregnancy-only gestational diabetes increased hazards by 76% (95% CI, 1.63-1.91), while gestational diabetes in both pregnancies increased it 3.63-fold (95% CI, 3.36-3.93). In this retrospective cohort study of nearly half a million women with 2 singleton pregnancies, both the number and ordinal pregnancy of any gestational diabetes occurrence increased diabetes risk. These considerations offer greater nuance than an ever or never gestational diabetes dichotomy.

Considering gestational diabetes and gestational hypertension history across two pregnancies in relationship to cardiovascular disease development: A retrospective cohort study

AimsGestational diabetes (GDM) and hypertension (GHTN) occurrences signal elevated cardiovascular disease (CVD) risk. There is little study of occurrence and recurrence of these conditions in relationship to CVD. Among women with two singleton pregnancies, we aimed to quantify CVD risk in relationship to the number of GDM/GHTN occurrences. MethodsIn this Quebec-based retrospective cohort study (n = 431,980), we ascertained the number of GDM/GHTN occurrences over two pregnancies and assessed for CVD over a median of 16.4 years (cohort inception 1990–2012, outcomes 1990–2019). We defined CVD as a composite of myocardial infarction, stroke, and angina, requiring hospitalization and/or causing death. We adjusted Cox proportional hazards models for offspring size, preterm/term birth status, maternal age group, time between deliveries, ethnicity, deprivation level, and co-morbid conditions. ResultsCompared to absence of GDM/GHTN in either pregnancy, one GDM/GHTN occurrence increased CVD hazards by 47% (hazard ratio [HR] = 1.47, 95% confidence interval [CI] 1.35–1.61), two occurrences nearly doubled hazards (HR = 1.91, 95% CI 1.68–2.17), and three or more approximately tripled CVD hazards (HR = 2.93, 95% CI 2.20–3.90). Individual components of the composite demonstrated similar findings. ConclusionsHealth care providers and mothers should consider a complete history of GDM/GHTN occurrences to ascertain the importance and urgency of preventive action.

Abstract 14127: Differential Stroke Volume Between Left and Right Ventricles as Predictor of Clinical Outcomes: The MESA Study

Background: Valvular heart diseases and intra-cardiac shunts associated with congenital heart disease can cause persistent disruption in the balance between left (LV) and right (RV) ventricular stroke volumes (SV). However, the prognostic value of such imbalances has not been established among asymptomatic individuals in the general population. Methods: 4,058 participants from multi-ethnic study of atherosclerosis who had a cardiac MRI at cohort inception were included in this study. ΔSV was calculated as LVSV-RVSV, and participants were classified as: Balanced ΔSV: -30 mL ≤ ΔSV ≤ 30 mL; Negative ΔSV: ΔSV &lt; -30 mL; and Positive ΔSV: ΔSV &gt; 30 mL. Multivariable Cox proportional hazard regression models were applied to compute hazard ratios for the association between ΔSV and mortality, heart failure (HF), and atrial fibrillation (AF). Results: The average age of participants was 61±10 years, with women making up 52% of the cohort. Participants were followed for a median of 17 years (IQR, 16.9-17.1) for AF, and 18.4 years (IQR, 18.3-18.5) for other outcomes. At baseline 1.2% of participants (n=47) had ΔSV &gt; 30 mL, 2% (n=80) had ΔSV &lt; -30 mL, and 96.8% (n=3931) had ΔSV between -30 and 30 mL. During follow up, 1,006 participants died, 235 incurred HF, and 764 developed AF. After adjusting for demographics and baseline cardiovascular risk factors, ΔSV &gt; 30 mL was associated with increased mortality (HR 1.73; 95% CI 1.12-2.67; p=0.01), HF (HR 2.40; 95% CI 1.11-5.20; p=0.02), and AF (HR 1.89; 95% CI 1.16-3.08; p=0.01). These relationships were independent of LV and RV function at baseline. ΔSV &lt; -30 mL solely linked to HF (HR 2.09, 95%CI 1.09-3.99; p=0.02) and lost significance after adjusting for baseline LV function. Conclusions: In a multi-ethnic cohort of participants free of cardiovascular disease at baseline, LVSV exceeding RVSV by at least 30 mL was independently associated with lower long-term survival and greater risk of HF and AF.

Opioid deprescribing in long-term care in Ontario: A comparison of resident and facility characteristics

Residents of long-term care (LTC) homes have potentially painful conditions and are prescribed opioids to manage their pain, despite the risks associated with the use of these high-risk medications. Therefore, the overall aim of this study was to describe the associations between resident and facility characteristics of residents prescribed long-term opioid therapy and those who remained on opioids or had opioids deprescribed. We conducted a retrospective cohort study utilizing health administrative databases housed within ICES. Our cohort included 26,592 of 121,564 LTC residents (21.9%) of Ontario LTC homes who were prescribed long-term opioid therapy at cohort inception. Of these residents, 4,299 (16.2%) residents had opioids deprescribed during the follow-up period. Opioid deprescribing was associated with younger age, high comorbidity, and co-prescription with benzodiazepines and gabapentinoids. Our findings suggest that there is variation in the characteristics of residents who continued long-term opioid therapy and those who subsequently had opioids deprescribed, and these characteristics need to be considered as part of individualized pain management plans of care.

Prevalence, incidence and associations of dementia with cardiovascular risk factors in the Latin American and Caribbean population. A population‐based cohort study of 10/66 Dementia Research Group

AbstractBackgroundLatin America and the Caribbean (LAC) countries are experiencing unprecedentedly rapid demographic ageing. Growing evidence shows that cardiovascular health (CVH) is associated with brain health. Little is known about this topic among older adults in Latin America, where the number of people living with dementia is rising. The present study aimed to examine the prevalence, incidence and associations of socioeconomic determinants and cardiovascular risk factors with dementia across six LAC countries.MethodsThe 10/66 Dementia Research Group has carried out population‐based catchment area surveys, using a common protocol, in six Latin‐American countries Cuba, Dominican Republic, Mexico, Peru, Puerto Rico and Venezuela of all over 65 year old (n = 12 704). An incidence wave was conducted 4 ‐5 years after cohort inception, 8 502 participants were reinter viewed, contributing 34 000 person‐years of follow‐up. The outcomes were 10/66 dementia and DSM IV dementia. An index of modifiable CVH factors (ranging from 0 to 14) was calculated. Incident dementia was modeled using competing risks regression to adjust for risk of death.ResultsThe prevalence of dementia varied widely across different countries, ranging from 4.8% in Peru and 11.7% in Puerto Rico and the Dominican Republic. Incidence of 10/66 dementia varied between 18.2 (95% CI 14.3‐23.0) per 1000 person‐years in Peru to 30.4 (25.5‐36.3) per 1000 person‐years in Mexico. Being male, having higher education and younger age were all protective of dementia. Specific cognitive tests including literacy, verbal fluency and motor sequencing had also similar protective associations with dementia, providing more supporting evidence for the cognitive reserve hypothesis. Compared to poor CVH, participants with moderate and ideal levels of CVH had a significantly lower risk of dementia both in the unadjusted (subhazard ratio for moderate: 0.77; ideal: 0.59) and adjusted models (moderate: 0.73; ideal: 0.66).ConclusionsThe prevalence of dementia in the older Latin American and Caribbean population is high. Moderate and ideal levels of CVH in old age may protect against dementia incidence. These findings may inform health promotion efforts within dementia national plans adopted recently in some Latin American countries

Prevalence and Factors Associated With Osteoporosis and Bone Mineral Density Testing in Psoriatic Arthritis.

To determine bone mineral density (BMD) in psoriatic arthritis (PsA) patients, factors associated with undergoing BMD testing, and the effect of PsA clinical activity on BMD. Patients attending the University of Toronto PsA Clinic with BMD testing results from cohort inception to January 2019 were included. Descriptive statistics summarized lumbar spine, femoral neck, and total hip T scores. Cox proportional hazards regression identified predictors for BMD testing. Logistic regression analysis determined odds of having normal (T score -1.0 or more) versus osteoporotic-range BMD (T score -2.5 or less). A multistate model determined factors associated with BMD state changes over time. Of the 1,479 patients, 214 had BMD tests performed. The mean ± SD T scores at the lumbar spine, femoral neck, and total hip were -0.30 ± 0.32, -1.10 ± 1.04, and -0.45 ± 0.42, respectively. Osteopenia and osteoporosis occurred in 45.27% and 12.94% of patients. Increasing age, menopause, elevated acute-phase reactants, and biologics, methotrexate, and systemic glucocorticoids use were associated with a higher chance of undergoing BMD testing. Increased body mass index (BMI) and biologics use were associated with a lower chance of having osteoporotic-range BMD test results. In multistate analysis, polyarthritis may portend lower BMD results over time, although this did not achieve statistical significance due to low patient numbers. The prevalence of osteopenia and osteoporosis in the PsA cohort was similar to that of the general population. Clinicians are using osteoporosis risk factors and PsA disease severity markers to select patients for BMD testing. Polyarticular disease may portend worse BMD test results. Biologic use and increased BMI appear to have a protective effect.

The effects of persistent sleep disturbances during early childhood over adolescent ADHD, and the mediating effect of attention-related executive functions: Data from the 2004 Pelotas Birth Cohort

ObjectiveInvestigate effects of persistent sleep disturbances during early childhood over ADHD during the adolescence, and the potential attention-related executive functions mediating this effect. MethodsWe used data from the 2004 Pelotas Birth Cohort. Children's Sleep disturbances were reported by their mothers at 12, 24, and 48 months of age, whereas the Test-of-Everyday-Attention-for-Children (TEA-Ch) and the Development and Well Being Assessment (DAWBA) were applied at 11 years of age to evaluate attention-related executive functions and ADHD, respectively. Persistent sleep problems were defined as reporting have two or more points of difficulty to sleep, nightmares, restless sleeps, and/or <10h/24h sleep duration. Logistic regression and mediation models were used, adjusting for maternal and child sociodemographic, behavior and health related variables. ResultsThe highest prevalence of adolescent ADHD (15.4%) was on the group who reported having nightmares at 2,4 and 6 years. In adjusted models, we observed an odd of ADHD in the adolescence 2.26 higher in those who reported persistent nightmares (CI95% 1.33, 4.01) compared to those reported transitory or no nightmares. Persistent difficulty to sleep (OR=1.74 CI95% 1.13, 2.66) and restless sleep (OR=1.80, CI95% 1.23, 2.64) during childhood also increased ADHD odds at 11 years. No indirect effect through attention related executive functions was found using mediating models. DiscussionPersistent early sleep disturbances may increase odds of ADHD among adolescents and could be consider as early marker of such disorder, specially nightmares problems. These effects were not mediated by attention-related executive functions. Nevertheless, we had 75% of cohort inception response.

Heterogeneity in Patient Characteristics and Differences in Treatment Across 4 Canadian Rheumatoid Arthritis Cohorts.

To compare clinical characteristics and treatment of patients with rheumatoid arthritis (RA) across 4 Canadian cohorts. The 4 longitudinal cohorts included the following: the Canadian Early Arthritis Cohort (CATCH; n = 2878), Ontario Best Practices Research Initiative (OBRI; n = 3734), RHUMADATA (Quebec, n = 2890), and the Rheum4U Precision Health Registry (Calgary, Alberta, n = 709). Data were from cohort inception (range 1998-2016) to 2020. Clinical characteristics and drug treatments were summarized descriptively. In total, 10,211 patients with RA were included. The percentage of patients who entered the cohort with early RA (2 yrs of disease at enrollment) ranged from 29% (Rheum4U) to 100% (CATCH). Mean age (55 yrs), sex (74% female), and seropositivity (69%) were similar between cohorts. At the time of initial disease-modifying antirheumatic drug (DMARD) use, median Disease Activity Score in 28 joints (DAS28) varied, ranging from 2.99 (Rheum4U) to 5.19 (CATCH), but were more similar at the time of the first DMARD switch (range 3.57-5.03), first biologic (bDMARD) or targeted synthetic DMARD (tsDMARD) use (range 4.01-4.67), and second bDMARD or tsDMARD (range 3.71-4.39). The initial DMARD was most commonly methotrexate, either in monotherapy (32%, range 18-40%) or dual therapy (34%, range 29-42%). The first DMARD switch was to another DMARD monotherapy in 20% (range 10-32%), dual therapy in 49% (range 39-56%), and bDMARD or tsDMARD in 24% (range 15-28%). The first bDMARD was an anti-tumor necrosis factor in 79% (range 78-82%). Canadian RA cohorts demonstrate some heterogeneity in treatment, which could reflect differences in inclusion criteria, calendar year, or regional differences. This project is a first step toward conducting harmonized analyses across Canadian RA cohorts.

Cancer incidence and mortality in the USA Astronaut Corps, 1959–2017

ObjectivesCancer incidence and mortality are important outcomes in the surveillance of long-term astronaut health. We compare cancer incidence rates, cancer-specific mortality rates, and cancer case-fatality ratios in US astronauts with...

Racial Differences in the Associations Between Food Insecurity and Fibroblast Growth Factor 23 in the Coronary Artery Risk Development in Young Adults Study

Food insecurity is associated with consumption of phosphate additive-laden processed food and beverage products, which could result in higher levels of fibroblast growth factor 23 (FGF23) to compensate for the increased dietary phosphate load. We sought to determine whether food insecurity is associated with higher levels of FGF23. We stratified analyses by race since differences may occur between food insecurity and diet quality across races. The longitudinal community-based Coronary Artery Risk Development in Young Adults Study recruited from 4 US centers: Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA, during the cohort inception in 1985/1986. This analysis included 3,421 black and white participants from Coronary Artery Risk Development in Young Adults follow-up years 20, 25, and 30 who were enrolled in the study between the ages of 18 and 30 years. Econometric fixed effects models stratified by race that adjust by design for all time-invariant covariates were used to model the longitudinal association of food insecurity, defined as the self-reported ability to afford desired quantity and quality of food. The main outcome of interest was changing to the highest quartile of plasma FGF-23 concentrations. During follow-up, 29% of blacks and 14% of whites experienced change in food security. Developing food insecurity was associated with a 1.48 greater odds of increasing to the highest quartile of FGF23 (95% confidence interval 1.02-2.15) among blacks; however, there was no significant longitudinal association among whites (odds ratio=1.14, 95% confidence interval 0.67-1.95). Among blacks, food insecurity was associated with an increase in levels of FGF23. Although phosphate consumption was presumed to mediate the association between food insecurity and FGF23 levels, we were unable to directly test this pathway.

Impact of prior stroke on major clinical outcome in chronic kidney disease: the Salford kidney cohort study

BackgroundChronic kidney disease (CKD) is an independent risk factor for stroke in the general population. The impact of prior stroke on major clinical outcomes in CKD populations is poorly characterised.MethodsThe Salford Kidney Study is a UK prospective cohort of more than 3000 patients recruited since 2002 and followed until March 2018. Multivariable Cox regression examined associations of stroke at two time points; cohort inception, and at dialysis initiation, with risks of death, non-fatal cardiovascular events (NFCVE) and end stage renal disease (ESRD).Results277 (9.1%) of 3060 patients suffered a prior stroke and this was associated with mortality, ESRD and future NFCVE after cardiovascular risk factor adjustments. Median survival for prior stroke patients was 40 months vs 77 months in patients without a stroke. Prior stroke was independently associated with mortality (HR 1.20 95%CI 1.0–1.43, p = 0.05). Of 579 patients who reached ESRD and commenced dialysis, a prior stroke (N = 48) was independently associated with mortality. Median survival for the prior stroke group was 29 months compared with 50 months for the non-stroke group. Only 70 and 75% of patients who had suffered an ischaemic stroke were prescribed antiplatelets or statins respectively.ConclusionsA diagnosis of stroke is strongly and independently associated with several adverse clinical outcomes for patients with CKD. Prior stroke profoundly alters cardiovascular risk in CKD patients. Greater attention to primary and secondary preventive strategies is warranted which may improve these outcomes.

Cancer in General Responders Participating in World Trade Center Health Programs, 2003-2013.

BackgroundFollowing the September 11, 2001, attacks on the World Trade Center (WTC), thousands of workers were exposed to an array of toxins known to cause adverse health effects, including cancer. This study evaluates cancer incidence in the WTC Health Program General Responder Cohort occurring within 12 years post exposure.MethodsThe study population consisted of 28 729 members of the General Responder Cohort enrolled from cohort inception, July 2002 to December 31, 2013. Standardized incidence ratios (SIRs) were calculated with cancer case inclusion and follow-up starting post September 11, 2001 (unrestricted) and, alternatively, to account for selection bias, with case inclusion and follow-up starting 6 months after enrollment in the WTC Health Program (restricted). Case ascertainment was based on linkage with six state cancer registries. Under the restricted criterion, hazard ratios were estimated using multivariable Cox proportional hazards models for all cancer sites combined and for prostate cancer.ResultsRestricted analyses identified 1072 cancers in 999 responders, with elevations in cancer incidence for all cancer sites combined (SIR = 1.09, 95% confidence interval [CI] = 1.02 to 1.16), prostate cancer (SIR = 1.25, 95% CI = 1.11 to 1.40), thyroid cancer (SIR = 2.19, 95% CI = 1.71 to 2.75), and leukemia (SIR = 1.41, 95% CI = 1.01 to 1.92). Cancer incidence was not associated with any WTC exposure index (composite or individual) for all cancer sites combined or for prostate cancer.ConclusionOur analyses show statistically significant elevations in cancer incidence for all cancer sites combined and for prostate and thyroid cancers and leukemia. Multivariable analyses show no association with magnitude or type of exposure.

Cohort profile: l’Actuel Pre-Exposure Prophylaxis (PrEP) Cohort study in Montreal, Canada

PurposeThe l’Actuel PrEP Cohort was established to monitor the uptake, effectiveness, safety and changes in sexual risk behaviours among individuals receiving pre-exposure prophylaxis (PrEP) for the prevention of HIV. This...

Considering parents as a unit: Associations of gestational diabetes and gestational hypertension with postpartum diabetes and hypertension in couples.

To evaluate the associations of a combined indicator of gestational diabetes mellitus (GDM) and gestational hypertension (GH) with diabetes and with hypertension in parental couples as a 'unit'. Utilizing administrative health data, GH was identified in matched pairs (GDM vs. no GDM) of mothers with singleton live births (Quebec, Canada; cohort inception 1990-2007). Couples were categorized based on GDM/GH status s ('neither'; 'either'; or 'both'). Using validated administrative health database definitions, associations of this indicator with diabetes and with hypertension in both members of the couple (12 weeks postpartum to March 31, 2012) were evaluated through adjusted Cox proportional hazard models. In 63,438 couples over a mean of 12.8 years (SD 5.4), diabetes risk was 9-fold higher (HR: 8.9; 95% CI 6.4, 12.2) in couples with either GDM/GH and 16-fold higher (HR 16.0; 95% CI 10.9, 23.5) in couples with both conditions compared to those with neither. Hypertension risk was 2-fold higher (HR: 1.8; 95% CI 1.5, 2.0) in couples either GDM/GH and 6-fold higher (HR 5.8; 95% CI 4.9, 7.0) in couples with both conditions compared to those with neither condition. GDM/GH predict diabetes and hypertension in couples as a unit underscoring the concept of shared couple risk. These findings may help foster couple collaboration for cardiovascular risk reduction in the household.

Association between gestational diabetes mellitus and depression in parents: a retrospective cohort study.

PurposeThe aim of this study was to examine the association between gestational diabetes mellitus (GDM) and depression incidence in mothers and fathers during prenatal and postnatal periods.Patients and methodsMatched pairs (GDM vs no GDM) of randomly selected mothers with singleton live births (matched by age group, delivery year, and health region) and their partners (Quebec, Canada; cohort inception 1990–2007) were assessed for a composite outcome of depression/self-harm/suicide using a health administrative database. We examined the association of GDM and the composite outcome in the following three nonoverlapping periods: 1) 24 weeks gestation up to delivery; 2) delivery up to 1 year postpartum; and 3) 1 year postpartum to study end (March 31, 2012). We used stratified Cox proportional regression hazards models, with three models in mothers and three models in fathers, corresponding to each of the time periods of interest.ResultsIn the 58,400 mothers, women with GDM had a nearly twofold greater risk (adjusted HR: 1.82, 95% CI 1.28, 2.59) of being diagnosed with depression compared to those without GDM during the prenatal period. In the first year postpartum, there was no conclusive difference observed between the two groups of mothers (adjusted HR: 1.05, 95% CI 0.84, 1.30). Beyond the first year postpartum, there was an 8% increased risk (adjusted HR: 1.08, 95% CI 1.03, 1.14) of depression in women with a history GDM compared to those without. A total of 63,384 fathers were included in our analyses, and no association between GDM in one’s partner and depression was found during any of the three time periods evaluated.ConclusionGDM is associated with an increased risk of depression in women particularly during pregnancy highlighting the need to screen for depression and provide supportive interventions during this period.

Systematic vs. on-demand early palliative care in gastric cancer patients: a randomized clinical trial assessing patient and healthcare service outcomes.

Early palliative care (EPC) has shown a positive impact on quality of life (QoL), quality of care, and healthcare costs. We evaluated such effects in patients with advanced gastric cancer. In this prospective, multicenter study, 186 advanced gastric cancer patients were randomized 1:1 to receive standard cancer care (SCC) plus on-demand EPC (standard arm) or SCC plus systematic EPC (interventional arm). Primary outcome was a change in QoL between randomization (T0) and T1 (12weeks after T0) in the Trial Outcome Index (TOI) scores evaluated through the Functional Assessment of Cancer Therapy-Gastric questionnaire. Secondary outcomes were patient mood, overall survival, and family satisfaction with healthcare and care aggressiveness. The mean change in TOI scores from T0 to T1 was - 1.30 (standard deviation (SD) 20.01) for standard arm patients and 1.65 (SD 22.38) for the interventional group, with a difference of 2.95 (95% CI - 4.43 to 10.32) (p= 0.430). The change in mean Gastric Cancer Subscale values for the standard arm was 0.91 (SD 14.14) and 3.19 (SD 15.25) for the interventional group, with a difference of 2.29 (95% CI - 2.80 to 7.38) (p= 0.375). Forty-three percent of patients in the standard arm received EPC. Our results indicated a slight, albeit not significant, benefit from EPC. Findings on EPC studies may be underestimated in the event of suboptimally managed issues: type of intervention, shared decision-making process between oncologists and PC physicians, risk of standard arm contamination, study duration, timeliness of assessment of primary outcomes, timeliness of cohort inception, and recruitment of patients with a significant symptom burden. ClinicalTrials.gov (NCT01996540).

Exposure to Ambient Air Pollution Associated with Increased Risk of Incident Diabetes Mellitus: A Population-Based Cohort Study

Background/Aim: Diabetes research has recently taken into consideration the potential influence of air pollution on diabetes risk. However, epidemiologic evidence linking air pollution to diabetes remains inconsistent. This study sought to assess the relationship between selected air pollutants (NO2, PM2.5, O3, and Ox [oxidant capacity]) and the incidence of diabetes.Methods: Our cohort consisted of ~4.8M adults aged 35 to 85 who were long-term Ontario residents prior to cohort inception in 2001. The cohort was followed until 2015. Long-term exposure to NO2, PM2.5, and O3 was estimated using satellite-based remote sensing, land-use regression model, and fusion-based approach, respectively, and was assigned to subjects&amp;#8217; annual postal code addresses. Ox was calculated as the redox-weighted average of O3 and NO2. Diabetes incidence was ascertained using population-based health administrative data with a validated algorithm. For each air pollutant, we estimated its association with diabetes using standard Cox proportional hazards models, adjusting for multiple individual-level and area-level covariates (e.g., SES and healthcare accessibility). We performed sensitivity and stratified analyses to assess the robustness of the estimates, and modelled the shape of air pollutant-diabetes associations using Shape Constrained Health Impact Functions.Results: Over the study period, 790,461 cohort members were diagnosed with diabetes. We found that each IQR increase in exposure to NO2 was associated with a hazard ratio of 1.06 (95% CI: 1.05-1.06). This relationship was relatively robust to sensitivity analyses considered, and exhibited a near-linear shape. There were positive associations between diabetes and PM2.5 (1.02 per IQR, 95% CI: 1.01-1.02), O3 (1.002 per IQR, 95% CI: 0.999-1.01), and Ox (1.01 per IQR, 95% CI: 1.01-1.01), but these estimates were sensitive to different models considered.Conclusions: Air pollution, especially NO2, was linked to increased diabetes risk.

Effects of ambient air pollution on incident Parkinson's disease in Ontario, 2001 to 2013: a population-based cohort study.

Despite recent studies linking air pollution to neurodegenerative illness, evidence relating air pollution and Parkinson's disease (PD) remains scarce. We conducted a population-based cohort study in Ontario, Canada, to determine the association between air pollution and incident PD. Using health administrative databases, we identified all adults aged 55-85 years, free of PD, and who lived in Ontario on 1 April 2001 (∼2.2 million). Individuals were followed up until 31 March 2013. We derived long-term average exposures to fine particulate matter (particles ≤2.5 µm in diameter, or PM2.5), nitrogen dioxide (NO2) and ozone from satellite-based estimates, land-use regression models and optimal interpolation methods, respectively. Using 2-year lags in exposures, we linked these estimates to individuals' annual postal codes from 1994 (7 years before cohort inception). We applied spatial random-effects Cox proportional hazards models, adjusting for individual- and area-level characteristics. We also performed sensitivity analyses, such as considering longer lags in exposures and stratifying by selected characteristics. During the study period, we identified 38745 newly diagnosed cases of PD. Each interquartile increment (3.8 µg/m3) of PM2.5 was associated with a 4% increase in incident PD (95% confidence interval, 1.01-1.08) after adjusting for various covariates. We also found positive associations for NO2 and ozone [hazard ratios (HRs) ranged from 1.03 to 1.04]. The associations for all exposures were unaltered with various sensitivity analyses except for considering longer lags, which somewhat attenuated the estimates, particularly for NO2 and ozone. Exposure to air pollution, especially PM2.5, was found to be related to incident PD.