Dose-dependent oral glucocorticoid cardiovascular risks in people with immune-mediated inflammatory diseases: A population-based cohort study

BackgroundGlucocorticoids are widely used to reduce disease activity and inflammation in patients with a range of immune-mediated inflammatory diseases. It is uncertain whether or not low to moderate glucocorticoid dose increases cardiovascular risk. We aimed to quantify glucocorticoid dose-dependent cardiovascular risk in people with 6 immune-mediated inflammatory diseases.Methods and findingsWe conducted a population-based cohort analysis of medical records from 389 primary care practices contributing data to the United Kingdom Clinical Practice Research Datalink (CPRD), linked to hospital admissions and deaths in 1998–2017. We estimated time-variant daily and cumulative glucocorticoid prednisolone-equivalent dose-related risks and hazard ratios (HRs) of first all-cause and type-specific cardiovascular diseases (CVDs). There were 87,794 patients with giant cell arteritis and/or polymyalgia rheumatica (n = 25,581), inflammatory bowel disease (n = 27,739), rheumatoid arthritis (n = 25,324), systemic lupus erythematosus (n = 3,951), and/or vasculitis (n = 5,199), and no prior CVD. Mean age was 56 years and 34.1% were men. The median follow-up time was 5.0 years, and the proportions of person–years spent at each level of glucocorticoid daily exposure were 80% for non-use, 6.0% for <5 mg, 11.2% for 5.0–14.9 mg, 1.6% for 15.0–24.9 mg, and 1.2% for ≥25.0 mg.Incident CVD occurred in 13,426 (15.3%) people, including 6,013 atrial fibrillation, 7,727 heart failure, and 2,809 acute myocardial infarction events. One-year cumulative risks of all-cause CVD increased from 1.4% in periods of non-use to 8.9% for a daily prednisolone-equivalent dose of ≥25.0 mg. Five-year cumulative risks increased from 7.1% to 28.0%, respectively. Compared to periods of non-glucocorticoid use, those with <5.0 mg daily prednisolone-equivalent dose had increased all-cause CVD risk (HR = 1.74; 95% confidence interval [CI] 1.64–1.84; range 1.52 for polymyalgia rheumatica and/or giant cell arteritis to 2.82 for systemic lupus erythematosus). Increased dose-dependent risk ratios were found regardless of disease activity level and for all type-specific CVDs. HRs for type-specific CVDs and <5.0-mg daily dose use were: 1.69 (95% CI 1.54–1.85) for atrial fibrillation, 1.75 (95% CI 1.56–1.97) for heart failure, 1.76 (95% CI 1.51–2.05) for acute myocardial infarction, 1.78 (95% CI 1.53–2.07) for peripheral arterial disease, 1.32 (95% CI 1.15–1.50) for cerebrovascular disease, and 1.93 (95% CI 1.47–2.53) for abdominal aortic aneurysm.The lack of hospital medication records and drug adherence data might have led to underestimation of the dose prescribed when specialists provided care and overestimation of the dose taken during periods of low disease activity. The resulting dose misclassification in some patients is likely to have reduced the size of dose–response estimates.ConclusionsIn this study, we observed an increased risk of CVDs associated with glucocorticoid dose intake even at lower doses (<5 mg) in 6 immune-mediated diseases. These results highlight the importance of prompt and regular monitoring of cardiovascular risk and use of primary prevention treatment at all glucocorticoid doses.

Mar Pujades-Rodriguez and colleagues investigate whether low dose steroids are associated with increased risks of cardiovascular diseases.     

Death of an offspring and parental risk of ischemic heart diseases: A population-based cohort study

BackgroundThe death of a child is an extreme life event with potentially long-term health consequences. Knowledge about its association with ischemic heart diseases (IHDs) and acute myocardial infarction (AMI), however, is very limited. We investigated whether the death of an offspring is associated with the risk of IHD and AMI.Methods and findingsWe studied parents of live-born children recorded in the Danish (1973 to 2016) and the Swedish (1973 to 2014) Medical Birth Registers (n = 6,711,952; mean age at baseline 31 years, 53% women). We retrieved information on exposure, outcomes, and covariates by linking individual-level information from several nationwide registers. We analyzed the abovementioned associations using Poisson regression. A total of 126,522 (1.9%) parents lost at least 1 child during the study period. Bereaved parents had a higher risk of IHD and AMI than the nonbereaved [incidence rate ratios (IRRs) (95% confidence intervals (CIs)): 1.20 (1.18 to 1.23), P < 0.001 and 1.21 (1.17 to 1.25), P < 0.001, respectively]. The association was present not only in case of losses due to CVD or other natural causes, but also in case of unnatural deaths. The AMI risk was highest in the first week after the loss [IRR (95% CI): 3.67 (2.08 to 6.46), P < 0.001], but a 20% to 40% increased risk was observed throughout the whole follow-up period. Study limitations include the possibility of residual confounding by socioeconomic, lifestyle, or health-related factors and the potentially limited generalizability of our findings outside Scandinavia.ConclusionsThe death of an offspring was associated with an increased risk of IHD and AMI. The finding that the association was present also in case of losses due to unnatural causes, which are less likely to be confounded by cardiovascular risk factors clustering in families, suggests that stress-related mechanisms may also contribute to the observed associations.

Dang Wei and co-workers study associations between offspring death and parental risk of adverse cardiac outcomes.     

Anemia and the onset of gout in a population-based cohort of adults: Atherosclerosis Risk in Communities study

Introduction

There is a growing prevalence of gout in the US and worldwide. Gout is a recognized risk factor for cardiovascular disease (CVD). It is unclear whether other risk factors for CVD are also associated with increased risk of gout. Anemia is one such CVD risk factor. No studies have evaluated the relationship between anemia and gout. We tested whether anemia was associated with incident gout independent of comorbid conditions in Atherosclerosis Risk in the Communities.

Methods

This population-based cohort recruited 15,792 individuals in 1987 to 1989 from four US communities and contained nine years of follow-up. Anemia was defined as hemoglobin <13.5 g/dL for men and <12 g/dL for women. Using a Cox Proportional Hazards model, we estimated the hazard ratio (HR) and confidence intervals (CI) of incident gout by baseline anemia, adjusted for confounders (sex, race, estimated glomerular filtration rate, body mass index and alcohol intake) and clinical factors (coronary heart disease, congestive heart failure, diabetes, hypertension, diuretic use and serum urate level).

Results

Among the 10,791 participants, 10% had anemia at baseline. There were 271 cases of incident gout. Patients with anemia had a two-fold increased risk of developing gout over nine years (HR = 2.01, 95% CI: 1.46, 2.76). Anemia was associated with incident gout independent of known gout risk factors, confounders and clinical risk factors (HR = 1.73, 95% CI: 1.24, 2.41). This association persisted after additionally adjusting for serum urate level (HR = 1.83, 95% CI: 1.30, 2.57).

Conclusion

We identified anemia as a novel risk factor for gout. Anemia was associated with an approximately two-fold increased risk of gout-independent kidney function and serum urate. These findings suggest that anemia is a risk factor for gout on par with other chronic conditions such as obesity and diabetes. The biological mechanism linking anemia to gout remains unclear.     

Aspirin use and chronic diseases: a cohort study of the elderly.

OBJECTIVE--To evaluate the associations between the use of aspirin and the incidences of cardiovascular diseases, cancers, and other chronic diseases. DESIGN--Postal questionnaire survey to elicit details of aspirin use. SETTING--Californian retirement community. SUBJECTS--All 22,781 residents of the community (white, affluent, and well educated) were sent a questionnaire that included questions on medical history and the use of drugs such as analgesics, laxatives, and vitamin supplements. In all 61% responded (13,987, 8881 women and 5106 men; median age 73). They formed the cohort that was followed up for 6 1/2 years using discharge summaries from three hospitals serving the area and death certificates from the health department. Only 13 respondents were lost to follow up but seemed not to have died. MAIN OUTCOME MEASURES--Incidences of cardiovascular diseases, cancers, gastrointestinal bleeding, ulcers, and cataracts were compared in participants who did and did not take aspirin daily. RESULTS--Age adjusted incidences were computed with an internal standard and five age groups. By 1 January 1988 there had been 25 incident cases of kidney cancer among all participants; 341 incident cases of stroke, 253 of acute myocardial infarction, 220 of ischaemic heart disease, and 317 of other heart disease were reported among respondents without a reported history of angina, myocardial infarction, or stroke. The incidence of kidney cancer was raised among those who took aspirin daily compared with those who did not take it, although the increase was significant only in men (relative risks = 6.3, 95% confidence interval 2.2 to 17, for men and 2.1, 0.53 to 8.5, for women). Those who took aspirin daily showed no increased risk of any other cancer, except colon cancer for both sexes combined (relative risk = 1.5, 1.1 to 2.2). The risk of acute myocardial infarction was reduced slightly among regular users of aspirin in men but not women. The risk of ischaemic heart disease was almost doubled in those who took aspirin daily compared with non-users (relative risks = 1.9, 1.1 to 3.1, for men and 1.7, 1.1 to 2.7, for women). Small, non-significant increased risks of stroke were observed in both sexes. CONCLUSION--The daily use of aspirin increased the risk of kidney cancer and ischaemic heart disease.     

Association of genetic liability to smoking initiation with e-cigarette use in young adults: A cohort study

BackgroundTobacco smoking and e-cigarette use are strongly associated, but it is currently unclear whether this association is causal, or due to shared factors that influence both behaviours such as a shared genetic liability. The aim of this study was to investigate whether polygenic risk scores (PRS) for smoking initiation are associated with ever use of e-cigarettes.Methods and findingsSmoking initiation PRS were calculated for young adults (N = 7,859, mean age = 24 years, 51% male) of European ancestry in the Avon Longitudinal Study of Parents and Children, a prospective birth cohort study initiated in 1991. PRS were calculated using the GWAS & Sequencing Consortium of Alcohol and Nicotine use (GSCAN) summary statistics. Five thresholds ranging from 5 × 10⁻⁸ to 0.5 were used to calculate 5 PRS for each individual. Using logistic regression, we investigated the association between smoking initiation PRS and the main outcome, self-reported e-cigarette use (n = 2,894, measured between 2016 and 2017), as well as self-reported smoking initiation and 8 negative control outcomes (socioeconomic position at birth, externalising disorders in childhood, and risk-taking in young adulthood). A total of 878 young adults (30%) had ever used e-cigarettes at 24 years, and 150 (5%) were regular e-cigarette users at 24 years. We observed positive associations of similar magnitude between smoking initiation PRS (created using the p < 5 × 10⁻⁸ threshold) and both smoking initiation (odds ratio (OR) = 1.29, 95% CI 1.19 to 1.39, p < 0.001) and ever e-cigarette use (OR = 1.24, 95% CI 1.14 to 1.34, p < 0.001) by the age of 24 years, indicating that a genetic predisposition to smoking initiation is associated with an increased risk of using e-cigarettes. At lower p-value thresholds, we observed an association between smoking initiation PRS and ever e-cigarette use among never smokers. We also found evidence of associations between smoking initiation PRS and some negative control outcomes, particularly when less stringent p-value thresholds were used to create the PRS, but also at the strictest threshold (e.g., gambling, number of sexual partners, conduct disorder at 7 years, and parental socioeconomic position at birth). However, this study is limited by the relatively small sample size and potential for collider bias.ConclusionsOur results indicate that there may be a shared genetic aetiology between smoking and e-cigarette use, and also with socioeconomic position, externalising disorders in childhood, and risky behaviour more generally. This indicates that there may be a common genetic vulnerability to both smoking and e-cigarette use, which may reflect a broad risk-taking phenotype.

Jasmine Khouja and co-workers study genetic predictors of tobacco smoking initiation and e-cigarette use.     

Associations of parental depression during adolescence with cognitive development in later life in China: A population-based cohort study

BackgroundPrior research has underscored negative impacts of perinatal parental depression on offspring cognitive performance in early childhood. However, little is known about the effects of parental depression during adolescence on offspring cognitive development.Methods and findingsThis study used longitudinal data from the nationally representative China Family Panel Studies (CFPS). The sample included 2,281 adolescents aged 10–15 years (the median age was 13 years with an interquartile range between 11 and 14 years) in 2012 when their parents were surveyed for depression symptoms with the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). The sample was approximately balanced by sex, with 1,088 females (47.7%). We examined the associations of parental depression in 2012 with offspring cognitive performance (measured by mathematics, vocabulary, immediate word recall, delayed word recall, and number series tests) in subsequent years (i.e., 2014, 2016, and 2018) using linear regression models, adjusting for various offspring (i.e., age, sex, and birth order), parent (i.e., parents’ education level, age, whether living with the offspring, and employment status), and household characteristics (i.e., place of residence, household income, and the number of offspring). We found parental depression during adolescence to be significantly associated with worse cognitive performance in subsequent years, in both crude and adjusted models. For example, in the crude models, adolescents whose mothers had depression symptoms in 2012 scored 1.0 point lower (95% confidence interval [CI]: −1.2 to −0.8, p < 0.001) in mathematics in 2014 compared to those whose mothers did not have depression symptoms; after covariate adjustment, this difference marginally reduced to 0.8 points (95% CI: −1.0 to −0.5, p < 0.001); the associations remained robust after further adjusting for offspring earlier cognitive ability in toddlerhood (−1.2, 95% CI: −1.6, −0.9, p < 0.001), offspring cognitive ability in 2012 (−0.6, 95% CI: −0.8, −0.3, p < 0.001), offspring depression status (−0.7, 95% CI: −1.0, −0.5, p < 0.001), and parents’ cognitive ability (−0.8, 95% CI: −1.2, −0.3, p < 0.001). In line with the neuroplasticity theory, we observed stronger associations between maternal depression and mathematical/vocabulary scores among the younger adolescents (i.e., 10–11 years) than the older ones (i.e., 12–15 years). For example, the association between maternal depression and 2014 vocabulary scores was estimated to be −2.1 (95% CI: −2.6, −1.6, p < 0.001) in those aged 10–11 years, compared to −1.2 (95% CI: −1.6, −0.8, p < 0.001) in those aged 12–15 years with a difference of 0.9 (95% CI: 0.2, 1.6, p = 0.010). We also observed a stronger association of greater depression severity with worse mathematical scores. The primary limitations of this study were the relatively high attrition rate and residual confounding.ConclusionsIn this study, we observed that parental depression during adolescence was associated with adverse offspring cognitive development assessed up to 6 years later. These findings highlight the intergenerational association between depression in parents and cognitive development across the early life course into adolescence.

In this cohort study, Zhihui Li and colleagues explore associations between parental depression and offspring cognitive development up to six years later.     

Antihypertensive medications and survival in patients with cancer: A population-based retrospective cohort study

Background: The association between antihypertensive medications and survival in cancer patients remains unclear. Objectives: To explore the association between classes of antihypertensive drugs and survival in cancer patients. Methods: Provincial Cancer Registry data was linked with a Provincial Drug Program Information Network (DPIN) for patients with lung (n = 4241), colorectal (n = 3967), breast (n = 4019) or prostate (n = 3355) cancer between the years of 2004 and 2008. Cox regression analyses were used to compare survival of patients using beta blockers (BBs), angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARB), calcium channel blockers (CCBs) or thiazide diuretics (TDs) to survival of patients who did not use any of these antihypertensive drugs. Survival of patients using only one class of antihypertensive drugs were compared to each other, with BBs as the reference class. Results: Compared to the antihypertensive drug non-user cohort, BBs had no effect on survival for any of the cancers. ACEi/ARBs use was weakly associated with increased deaths for breast cancer (HR: 1.22, 95% CI: 1.04–1.44) and lung cancer (HR: 1.11, 95% CI: 1.03–1.21) patients. Deaths were also increased with CCB use in patients with breast cancer (HR: 1.22, 95% CI: 1.02–1.47) and with TD use in lung cancer patients (HR: 1.1, 95% CI: 1.01–1.19). There was strong evidence (p-value <0.0001) of an increase in deaths with TD use for colorectal (HR: 1.28, 95% CI: 1.15–1.42), and prostate (HR 1.41, 1.2–1.65) cancer patients. When including only antihypertensive drug users prescribed one drug class, lung cancer patients receiving CCBs had improved survival compared to BBs (HR 0.79, 95% CI: 0.64–0.98). Conclusions: Some classes of antihypertensive agents are associated with a decreased survival in certain cancers. The decrease could be due to more comorbidities in antihypertensive drug users. However, CCB use was associated with improved survival in lung cancer patients.     

Rates of health services use among residents of retirement homes in Ontario: a population-based cohort study

Background:Because there are no standardized reporting systems specific to residents of retirement homes in North America, little is known about the health of this distinct population of older adults. We evaluated rates of health services use by residents of retirement homes relative to those of residents of long-term care homes and other populations of older adults.Methods:We conducted a retrospective cohort study using population health administrative data from 2018 on adults 65 years or older in Ontario. We matched the postal codes of individuals to those of licensed retirement homes to identify residents of retirement homes. Outcomes included rates of hospital-based care and physician visits.Results:We identified 54 733 residents of 757 retirement homes (mean age 86.7 years, 69.0% female) and 2 354 385 residents of other settings. Compared to residents of long-term care homes, residents of retirement homes had significantly higher rates per 1000 person months of emergency department visits (10.62 v. 4.48, adjusted relative rate [RR] 2.61, 95% confidence interval [CI] 2.55 to 2.67), hospital admissions (5.42 v. 2.08, adjusted RR 2.77, 95% CI 2.71 to 2.82), alternate level of care (ALC) days (6.01 v. 2.96, adjusted RR 1.51, 95% CI 1.48 to 1.54), and specialist physician visits (6.27 v. 3.21, adjusted RR 1.64, 95% CI 1.61 to 1.68), but a significantly lower rate of primary care visits (16.71 v. 108.47, adjusted RR 0.13, 95% CI 0.13 to 0.14).Interpretation:Residents of retirement homes are a distinct population with higher rates of hospital-based care. Our findings can help to inform policy debates about the need for more coordinated primary and supportive health care in privately operated congregate care homes.

In the continuum of care services and settings for older adults lies home care at one end and long-term care at the other.¹ Home care services may include, but are not limited to, nursing care, personal care, homemaking services, and physiotherapy and occupational therapy for older adults who live independently in their community. Home care services are publicly funded under the Ontario Health Insurance Plan (OHIP).^2,3 Long-term care homes provide access to 24-hour nursing and personal care and operate at full capacity in Ontario, with waiting lists of 6 months or longer before an older adult in the community could receive an offer for a bed.^2,4 Retirement homes are thought to fit between home care and long-term care in this continuum.¹Retirement homes are referred to as assisted-living facilities in other North American jurisdictions, and they are private, congregate living environments that deliver supportive care to adults who are 65 years of age and older.^3,5,6 These homes are often marketed to provide a lifestyle and community, and they provide a range of assisted-living care services (e.g., meals, nursing services, etc.).^5,7 Retirement homes predominately operate on a private, for-profit business model, and the room, board and services are purchased by residents.^3,5 In Ontario, retirement homes are regulated through an independent, not-for-profit regulator (i.e., Retirement Homes Regulatory Authority [RHRA]).⁵ There are more than 700 licensed retirement homes in Ontario with over 70 000 available beds occupied by over 55 000 residents, which is comparable to the number of available beds in the long-term care sector.^3,5,6,8 Retirement homes are legislated differently from long-term care homes and primarily cater to adults who do not require 24-hour nursing care.^1,5,9 Unlike long-term care homes, no standardized reporting system is available to identify and describe residents of retirement homes.¹⁰ These residents are conceptualized as having fewer needs for care because they reside in a congregate care home to support independent living; however, this has been difficult to verify given there are no population-level data.A body of literature from the United States has described residents of assisted-living facilities and the sector,^11–17 but Canadian literature is comparatively nascent. Canadian studies have investigated transitions to a long-term care home, risk of hospital admission among those who live with dementia, and life events and health conditions associated with the transition to a congregate care setting.^7,9,18–20 At present, a Canadian population-level cohort of residents of retirement homes that describes the individual-level characteristics and use of health services of the older adults who reside in these homes appears to be lacking. Therefore, it is difficult to position this sector in the gradient of services and housing options for older adults in Canada.We created a population-level cohort of residents in retirement homes and sought to evaluate their rates of health services utilization relative to residents of long-term care homes and other populations of older adults (i.e., home care recipients and community-dwelling older adults) in Ontario.     

Association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous,arterial, or thrombocytopenic events: A population-based cohort study of 46 million adults in England

BackgroundThromboses in unusual locations after the Coronavirus Disease 2019 (COVID-19) vaccine ChAdOx1-S have been reported, although their frequency with vaccines of different types is uncertain at a population level. The aim of this study was to estimate the population-level risks of hospitalised thrombocytopenia and major arterial and venous thromboses after COVID-19 vaccination.Methods and findingsIn this whole-population cohort study, we analysed linked electronic health records from adults living in England, from 8 December 2020 to 18 March 2021. We estimated incidence rates and hazard ratios (HRs) for major arterial, venous, and thrombocytopenic outcomes 1 to 28 and >28 days after first vaccination dose for ChAdOx1-S and BNT162b2 vaccines. Analyses were performed separately for ages <70 and ≥70 years and adjusted for age, age², sex, ethnicity, and deprivation. We also prespecified adjustment for anticoagulant medication, combined oral contraceptive medication, hormone replacement therapy medication, history of pulmonary embolism or deep vein thrombosis, and history of coronavirus infection in analyses of venous thrombosis; and diabetes, hypertension, smoking, antiplatelet medication, blood pressure lowering medication, lipid lowering medication, anticoagulant medication, history of stroke, and history of myocardial infarction in analyses of arterial thromboses. We selected further covariates with backward selection.Of 46 million adults, 23 million (51%) were women; 39 million (84%) were <70; and 3.7 million (8.1%) Asian or Asian British, 1.6 million (3.5%) Black or Black British, 36 million (79%) White, 0.7 million (1.5%) mixed ethnicity, and 1.5 million (3.2%) were of another ethnicity. Approximately 21 million (46%) adults had their first vaccination between 8 December 2020 and 18 March 2021.The crude incidence rates (per 100,000 person-years) of all venous events were as follows: prevaccination, 140 [95% confidence interval (CI): 138 to 142]; ≤28 days post-ChAdOx1-S, 294 (281 to 307); >28 days post-ChAdOx1-S, 359 (338 to 382), ≤28 days post-BNT162b2-S, 241 (229 to 253); >28 days post-BNT162b2-S 277 (263 to 291). The crude incidence rates (per 100,000 person-years) of all arterial events were as follows: prevaccination, 546 (95% CI: 541 to 555); ≤28 days post-ChAdOx1-S, 1,211 (1,185 to 1,237); >28 days post-ChAdOx1-S, 1678 (1,630 to 1,726), ≤28 days post-BNT162b2-S, 1,242 (1,214 to 1,269); >28 days post-BNT162b2-S, 1,539 (1,507 to 1,572).Adjusted HRs (aHRs) 1 to 28 days after ChAdOx1-S, compared with unvaccinated rates, at ages <70 and ≥70 years, respectively, were 0.97 (95% CI: 0.90 to 1.05) and 0.58 (0.53 to 0.63) for venous thromboses, and 0.90 (0.86 to 0.95) and 0.76 (0.73 to 0.79) for arterial thromboses. Corresponding aHRs for BNT162b2 were 0.81 (0.74 to 0.88) and 0.57 (0.53 to 0.62) for venous thromboses, and 0.94 (0.90 to 0.99) and 0.72 (0.70 to 0.75) for arterial thromboses. aHRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines.Rates of intracranial venous thrombosis (ICVT) and of thrombocytopenia in adults aged <70 years were higher 1 to 28 days after ChAdOx1-S (aHRs 2.27, 95% CI: 1.33 to 3.88 and 1.71, 1.35 to 2.16, respectively), but not after BNT162b2 (0.59, 0.24 to 1.45 and 1.00, 0.75 to 1.34) compared with unvaccinated. The corresponding absolute excess risks of ICVT 1 to 28 days after ChAdOx1-S were 0.9 to 3 per million, varying by age and sex.The main limitations of the study are as follows: (i) it relies on the accuracy of coded healthcare data to identify exposures, covariates, and outcomes; (ii) the use of primary reason for hospital admission to measure outcome, which improves the positive predictive value but may lead to an underestimation of incidence; and (iii) potential unmeasured confounding.ConclusionsIn this study, we observed increases in rates of ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years that were small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults aged <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic events were generally lower after either vaccine compared with unvaccinated, suggesting that either vaccine is suitable in this age group.

In a population-based cohort study, William Whiteley and colleagues investigate the association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, or thrombocytopenic events in England.     

Cancer risk in individuals with intellectual disability in Sweden: A population-based cohort study

BackgroundA knowledge gap exists about the risk of cancer in individuals with intellectual disability (ID). The primary aim of this study was to estimate the cancer risk among individuals with ID compared to individuals without ID.Methods and findingsWe conducted a population-based cohort study of all children live-born in Sweden between 1974 and 2013 and whose mothers were born in a Nordic country. All individuals were followed from birth until cancer diagnosis, emigration, death, or 31 December 2016 (up to age 43 years), whichever came first. Incident cancers were identified from the Swedish Cancer Register. We fitted Cox regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) as measures of cancer risk in relation to ID after adjusting for several potential confounders. We analyzed ID by severity, as well as idiopathic ID and syndromic ID separately. We performed a sibling comparison to investigate familial confounding. The study cohort included a total of 3,531,305 individuals, including 27,956 (0.8%) individuals diagnosed with ID. Compared with the reference group (individuals without ID and without a full sibling with ID), individuals with ID were in general more likely to be male. The median follow-up time was 8.9 and 23.0 years for individuals with ID and individuals without ID, respectively. A total of 188 cancer cases were identified among individuals with ID (incidence rate [IR], 62 per 1,000 person-years), and 24,960 among individuals in the reference group (IR, 31 per 1,000 person-years). A statistically significantly increased risk was observed for any cancer (HR 1.57, 95% CI 1.35–1.82; P < 0.001), as well as for several cancer types, including cancers of the esophagus (HR 28.4, 95% CI 6.2–130.6; P < 0.001), stomach (HR 6.1, 95% CI 1.5–24.9; P = 0.013), small intestine (HR 12.0, 95% CI 2.9–50.1; P < 0.001), colon (HR 2.0, 95% CI 1.0–4.1; P = 0.045), pancreas (HR 6.0, 95% CI 1.5–24.8; P = 0.013), uterus (HR 11.7, 95% CI 1.5–90.7; P = 0.019), kidney (HR 4.4, 95% CI 2.0–9.8; P < 0.001), central nervous system (HR 2.7, 95% CI 2.0–3.7; P < 0.001), and other or unspecified sites (HR 4.8, 95% CI 1.8–12.9; P = 0.002), as well as acute lymphoid leukemia (HR 2.4, 95% CI 1.3–4.4; P = 0.003) and acute myeloid leukemia (HR 3.0, 95% CI 1.4–6.4; P = 0.004). Cancer risk was not modified by ID severity or sex but was higher for syndromic ID. The sibling comparison showed little support for familial confounding. The main study limitations were the limited statistical power for the analyses of specific cancer types, and the potential for underestimation of the studied associations (e.g., due to potential underdetection or delayed diagnosis of cancer among individuals with ID).ConclusionsIn this study, we found that individuals with ID showed an increased risk of any cancer, as well as of several specific cancer types. These findings suggest that extended surveillance and early intervention for cancer among individuals with ID are warranted.

In a nationwide cohort study in Sweden, Qianwei Liu and co-workers report on cancer risk in people with intellectual disability.     

Elevated plasma vitamin B12 levels and cancer prognosis: A population-based cohort study

BackgroundElevated plasma vitamin B12 levels (cobalamin, Cbl) are associated with increased short-term cancer risk among patients referred for this laboratory measurement. We aimed to assess prognosis in cancer patients with elevated plasma Cbl.MethodsWe conducted a population-based cohort study using data from Danish medical registries during 1998–2014. The study included 25,017 patients with a cancer diagnosis and Cbl levels of 200–600 pmol/L (reference/normal range), 601–800 pmol/L and >800 pmol/L measured up to one year prior to diagnosis, and a comparison cohort of 61,988 cancer patients without a plasma Cbl measurement. Patients treated with Cbl were excluded. Survival probability was assessed using Kaplan–Meier curves. Mortality risk ratios (MRR) were computed using Cox proportional hazard regression, adjusted for age, sex, calendar year, cancer stage and comorbidity, scored using the Charlson comorbidity index.ResultsSurvival probabilities were lower among patients with elevated Cbl levels than among patients with normal levels and among members of the comparison cohort [(1-year survival,%) Cbl: 200–600 pmol/L: 69.3%; 601–800 pmol/L: 49.6%; >800 pmol/L: 35.8%; comparison cohort: 72.6%]. Thirty-day mortality was elevated for patients with Cbl levels of 601–800 pmol/L or >800 pmol/L, compared to patients with levels of 200–600 pmol/L [(MRR (95% confidence interval): 601–800 pmol/L vs. 200–600 pmol/L: 1.9 (1.6–2.2); >800 pmol/L vs. 200–600 pmol/L: 2.7 (2.4–3.1)]. This association remained robust for 31–90-day and 91–365-day mortality, showing similar dose-response patterns.ConclusionCancer patients with elevated Cbl levels had higher mortality than those with normal Cbl levels. These findings may have clinical significance for assessing the prognosis of cancer patients.     

Cholesterol-lowering drugs and incident open-angle glaucoma: a population-based cohort study

Background

Open-angle glaucoma (OAG) is a progressive neurodegenerative disease that may lead to blindness. An elevated intraocular pressure (IOP) is its major risk factor. OAG treatment is currently exclusively directed towards the lowering of the IOP. IOP lowering does not prevent disease progression in all patients and thus other treatment modalities are needed. Earlier studies reported cholesterol-lowering drugs to have neuroprotective properties. The aim of this study was to determine the associations between the use of cholesterol-lowering drugs and incident OAG.

Methodology/Principal Findings

Participants in a prospective population-based cohort study underwent ophthalmic examinations, including IOP measurements and perimetry, at baseline and follow-up. The use of statins and non-statin cholesterol-lowering drugs was monitored continuously during the study. Associations between the use of cholesterol-lowering drugs and incident OAG were analyzed with Cox regression; associations between cholesterol-lowering drugs and IOP at follow-up were analyzed with multiple linear regression. During a mean follow-up of 9.8 years, 108 of 3939 eligible participants (2.7%) developed OAG. The hazard ratio for statin use was 0.54 (95% confidence interval 0.31–0.96; P = 0.034) and for non-statin cholesterol-lowering drugs 2.07 (0.81–5.33; P = 0.13). The effect of statins was more pronounced with prolonged use (hazard ratio 0.89 [0.41–1.94; P = 0.77] for use two years or less; 0.46 [0.23–0.94; P = 0.033] for use more than two years; P-value for trend 0.10). The analyzes were adjusted for age and gender, baseline IOP and IOP-lowering treatment, the family history of glaucoma, and myopia. There was no effect of statins on the IOP.

Conclusions/Significance

Long-term use of statins appears to be associated with a reduced risk of OAG. The observed effect was independent of the IOP. These findings are in line with the idea that statins have neuroprotective properties and may open a way to a new OAG treatment modality.     

The relationship between congenital heart disease and cancer in Swedish children: A population-based cohort study

BackgroundBirth defects have been consistently associated with elevated childhood cancer risks; however, the relationship between congenital heart disease (CHD) and childhood cancer remains conflicting. Considering the increasing patient population with CHD after improvements in their life expectancies, insights into this relationship are particularly compelling. Thus, we aimed to determine the relationship between CHD and cancer in Swedish children.Methods and findingsAll individuals registered in the Swedish Medical Birth Register (MBR) between 1973 and 2014 were included in this population–based cohort study (n = 4,178,722). Individuals with CHD (n = 66,892) were identified from the MBR and National Patient Register, whereas cancer diagnoses were retrieved from the Swedish Cancer Register. The relationship between CHD and childhood cancer (<20 years at diagnosis) was evaluated using Cox proportional hazards regression models. We observed increased risks of cancer overall, leukemia, lymphoma, and hepatoblastoma in children with CHD, but after adjustment for Down syndrome, only the increased lymphoma (hazard ratio (HR) = 1.64, 95% confidence interval (CI) 1.11 to 2.44) and hepatoblastoma (HR = 3.94, 95% CI 1.83 to 8.47) risk remained. However, when restricting to CHD diagnoses from the MBR only, i.e., those diagnosed around birth, the risk for childhood cancer overall (HR = 1.45, 95% CI 1.23 to 1.71) and leukemia (HR = 1.41, 95% CI 1.08 to 1.84) was more pronounced, even after controlling for Down syndrome. Finally, a substantially elevated lymphoma risk (HR = 8.13, 95% CI 4.06 to 16.30) was observed in children with complex CHD. Limitations of the study include the National Patient Register not being nationwide until 1987, in addition to the rareness of the conditions under study providing limited power for analyses on the rarer cancer subtypes.ConclusionsWe found associations between CHD and childhood lymphomas and hepatoblastomas not explained by a diagnosis of Down syndrome. Stronger associations were observed in complex CHD.

Christina-Evmorfia Kampitsi and colleagues investigate the relationship between congenital heart disease and cancer in Swedish children.     

Childhood leukemia mortality and farming exposure in South Korea: A national population-based birth cohort study

ObjectivesThe aim of this study was to evaluate the relationship between leukemia mortality and exposure to farming among children in South Korea.MethodsA retrospective cohort study of South Korean children was conducted using data collected by the national birth register between 1995 and 2006; these data were then individually linked to death data. A cohort of 6,479,406 children was followed from birth until either their death or until December 31, 2006. For surrogate measures of pesticide exposure, we used residence at birth, paternal occupation, and month of conception from the birth certificate. Farming and pesticide exposure indexes by county were calculated using information derived from the 2000 agricultural census. Poisson regression analyses were used to calculate rate ratios (RRs) of childhood leukemia deaths according to indices of exposure to agricultural pesticides after adjustment for potential confounders.ResultsIn total 585 leukemia deaths were observed during the study period. Childhood leukemia mortality was significantly elevated in children born in rural areas (RR = 1.43, 95%CI 1.09–1.86) compared to those in metropolises, and in counties with both the highest farming index (RR = 1.33, 95%CI 1.04–1.69) and pesticide exposure index (RR = 1.30, 95%CI 1.02–1.66) compared to those in the reference group. However, exposure–response associations were significant only in relation to the farming index. When the analyses were limited to rural areas, the risk of death from leukemia among boys conceived between spring and fall increased over those conceived in winter.ConclusionsOur results show an increase in mortality from childhood leukemia in rural areas; however, further studies are warranted to investigate the environmental factors contributing to the excess mortality from childhood leukemia in rural areas.