Mortality and major disease risk among migrants of the 1991–2001 Balkan wars to Sweden: A register-based cohort study

BackgroundIn recent decades, millions of refugees and migrants have fled wars and sought asylum in Europe. The aim of this study was to quantify the risk of mortality and major diseases among migrants during the 1991–2001 Balkan wars to Sweden in comparison to other European migrants to Sweden during the same period.Methods and findingsWe conducted a register-based cohort study of 104,770 migrants to Sweden from the former Yugoslavia during the Balkan wars and 147,430 migrants to Sweden from 24 other European countries during the same period (1991–2001). Inpatient and specialized outpatient diagnoses of cardiovascular disease (CVD), cancer, and psychiatric disorders were obtained from the Swedish National Patient Register and the Swedish Cancer Register, and mortality data from the Swedish Cause of Death Register. Adjusting for individual-level data on sociodemographic characteristics and emigration country smoking prevalence, we used Cox regressions to contrast risks of health outcomes for migrants of the Balkan wars and other European migrants. During an average of 12.26 years of follow-up, being a migrant of the Balkan wars was associated with an elevated risk of being diagnosed with CVD (HR 1.39, 95% CI 1.34–1.43, p < 0.001) and dying from CVD (HR 1.45, 95% CI 1.29–1.62, p < 0.001), as well as being diagnosed with cancer (HR 1.16, 95% CI 1.08–1.24, p < 0.001) and dying from cancer (HR 1.27, 95% CI 1.15–1.41, p < 0.001), compared to other European migrants. Being a migrant of the Balkan wars was also associated with a greater overall risk of being diagnosed with a psychiatric disorder (HR 1.19, 95% CI 1.14–1.23, p < 0.001), particularly post-traumatic stress disorder (HR 9.33, 95% CI 7.96–10.94, p < 0.001), while being associated with a reduced risk of suicide (HR 0.68, 95% CI 0.48–0.96, p = 0.030) and suicide attempt (HR 0.57, 95% CI 0.51–0.65, p < 0.001). Later time period of migration and not having any first-degree relatives in Sweden at the time of immigration were associated with greater increases in risk of CVD and psychiatric disorders. Limitations of the study included lack of individual-level information on health status and behaviors of migrants at the time of immigration.ConclusionsOur findings indicate that migrants of the Balkan wars faced considerably elevated risks of major diseases and mortality in their first decade in Sweden compared to other European migrants. War migrants without family members in Sweden or with more recent immigration may be particularly vulnerable to adverse health outcomes. Results underscore that persons displaced by war are a vulnerable group in need of long-term health surveillance for psychiatric disorders and somatic disease.

Edda Bjork Thordardottir and co-workers study health outcomes among migrants from the former Yugoslavia to Sweden.     

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.     

Effectiveness of knowledge brokering and recommendation dissemination for influencing healthcare resource allocation decisions: A cluster randomised controlled implementation trial

BackgroundImplementing evidence into clinical practice is a key focus of healthcare improvements to reduce unwarranted variation. Dissemination of evidence-based recommendations and knowledge brokering have emerged as potential strategies to achieve evidence implementation by influencing resource allocation decisions. The aim of this study was to determine the effectiveness of these two research implementation strategies to facilitate evidence-informed healthcare management decisions for the provision of inpatient weekend allied health services.Methods and findingsThis multicentre, single-blinded (data collection and analysis), three-group parallel cluster randomised controlled trial with concealed allocation was conducted in Australian and New Zealand hospitals between February 2018 and January 2020. Clustering and randomisation took place at the organisation level where weekend allied health staffing decisions were made (e.g., network of hospitals or single hospital). Hospital wards were nested within these decision-making structures. Three conditions were compared over a 12-month period: (1) usual practice waitlist control; (2) dissemination of written evidence-based practice recommendations; and (3) access to a webinar-based knowledge broker in addition to the recommendations. The primary outcome was the alignment of weekend allied health provision with practice recommendations at the cluster and ward levels, addressing the adoption, penetration, and fidelity to the recommendations. The secondary outcome was mean hospital length of stay at the ward level. Outcomes were collected at baseline and 12 months later. A total of 45 clusters (n = 833 wards) were randomised to either control (n = 15), recommendation (n = 16), or knowledge broker (n = 14) conditions. Four (9%) did not provide follow-up data, and no adverse events were recorded. No significant effect was found with either implementation strategy for the primary outcome at the cluster level (recommendation versus control β 18.11 [95% CI −8,721.81 to 8,758.02] p = 0.997; knowledge broker versus control β 1.24 [95% CI −6,992.60 to 6,995.07] p = 1.000; recommendation versus knowledge broker β −9.12 [95% CI −3,878.39 to 3,860.16] p = 0.996) or ward level (recommendation versus control β 0.01 [95% CI 0.74 to 0.75] p = 0.983; knowledge broker versus control β −0.12 [95% CI −0.54 to 0.30] p = 0.581; recommendation versus knowledge broker β −0.19 [−1.04 to 0.65] p = 0.651). There was no significant effect between strategies for the secondary outcome at ward level (recommendation versus control β 2.19 [95% CI −1.36 to 5.74] p = 0.219; knowledge broker versus control β −0.55 [95% CI −1.16 to 0.06] p = 0.075; recommendation versus knowledge broker β −3.75 [95% CI −8.33 to 0.82] p = 0.102). None of the control or knowledge broker clusters transitioned to partial or full alignment with the recommendations. Three (20%) of the clusters who only received the written recommendations transitioned from nonalignment to partial alignment. Limitations include underpowering at the cluster level sample due to the grouping of multiple geographically distinct hospitals to avoid contamination.ConclusionsOwing to a lack of power at the cluster level, this trial was unable to identify a difference between the knowledge broker strategy and dissemination of recommendations compared with usual practice for the promotion of evidence-informed resource allocation to inpatient weekend allied health services. Future research is needed to determine the interactions between different implementation strategies and healthcare contexts when translating evidence into healthcare practice.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12618000029291.

In a cluster randomized controlled implementation trial, Dr. Mitchell N Sarkies and colleagues examine the effectiveness of knowledge brokering and recommendation dissemination in influencing healthcare resource allocation decisions in Australia and New Zealand.     

Is There an Association between Traumatic Dental Injury and Social Capital,Binge Drinking and Socioeconomic Indicators among Schoolchildren?

ObjectivesTraumatic dental injury is defined as trauma caused by forces on a tooth with variable extent and severity. The aim of the present study was to investigate the prevalence of traumatic dental injury and its association with overjet, lip protection, sex, socioeconomic status, social capital and binge drinking among 12-year-old students.ResultsThe prevalence of traumatic dental injury was 29.9% (176/588). Traumatic dental injury was more prevalent among male adolescents (p = 0.010), those with overjet greater than 5 mm (p < 0.001) and those with inadequate lip protection (p < 0.001). In the multiple logistic regression analysis, overjet [OR = 3.80 (95% CI: 2.235–6.466), p < 0.0001], inadequate lip protection [OR = 5.585 (95% CI: 3.654–8.535), p < 0.0001] and binge drinking [OR = 1.93 (95% CI: 1.21–3.06), p = 0.005] remained significantly associated with traumatic dental injury.ConclusionsThe present findings suggest that a high level of total social capital and trust are not associated with TDI in adolescents, unlike binge drinking. The effects of social and behavioral factors on TDI are not well elucidated. Therefore, further research involving other populations and a longitudinal design is recommended.     

Antenatal corticosteroid administration and early school age child development: A regression discontinuity study in British Columbia,Canada

BackgroundThere are growing concerns that antenatal corticosteroid administration may harm children’s neurodevelopment. We investigated the safety of antenatal corticosteroid administration practices for children’s overall developmental health (skills and behaviors) at early school age.Methods and findingsWe linked population health and education databases from British Columbia (BC), Canada to identify a cohort of births admitted to hospital between 31 weeks, 0 days gestation (31+0 weeks), and 36+6 weeks, 2000 to 2013, with routine early school age child development testing. We used a regression discontinuity design to compare outcomes of infants admitted just before and just after the clinical threshold for corticosteroid administration of 34+0 weeks. We estimated the median difference in the overall Early Development Instrument (EDI) score and EDI subdomain scores, as well as risk differences (RDs) for special needs designation and developmental vulnerability (<10th percentile on 2 or more subdomains). The cohort included 5,562 births admitted between 31+0 and 36+6 weeks, with a median EDI score of 40/50. We found no evidence that antenatal corticosteroid administration practices were linked with altered child development at early school age: median EDI score difference of −0.5 [95% CI: −2.2 to 1.7] (p = 0.65), RD per 100 births for special needs designation −0.5 [−4.2 to 3.1] (p = 0.96) and for developmental vulnerability of 3.9 [95% CI:−2.2 to 10.0] (p = 0.24). A limitation of our study is that the regression discontinuity design estimates the effect of antenatal corticosteroid administration at the gestational age of the discontinuity, 34 + 0 weeks, so our results may become less generalisable as gestational age moves further away from this point.ConclusionsOur study did not find that that antenatal corticosteroid administration practices were associated with child development at early school age. Our findings may be useful for supporting clinical counseling about antenatal corticosteroids administration at late preterm gestation, when the balance of harms and benefits is less clear.

Using a regression discontinuity design, Jennifer Hutcheon and colleagues investigate the relationship between corticosteroid treatment before birth and school-age child development in British Columbia, Canada.     

Effectiveness of a brief group behavioural intervention on psychological distress in young adolescent Syrian refugees: A randomised controlled trial

BackgroundMillions of young adolescents in low- and middle-income countries (LMICs) affected by humanitarian crises experience elevated rates of poor mental health. There is a need for scalable programs that can improve the mental health of young adolescents. This study evaluated the effectiveness of a nonspecialist delivered group-based intervention (Early Adolescent Skills for Emotions (EASE)) to improve young adolescents’ mental health.Methods and findingsIn this single-blind, parallel, controlled trial, Syrian refugees aged 10 to 14 years in Jordan were identified through screening of psychological distress as defined by scores ≥15 on the Paediatric Symptom Scale. Participants were randomised to either EASE or enhanced usual care (EUC) involving referral to local psychosocial services (on a 1:1.6 ratio). Participants were aware of treatment allocation but assessors were blinded. Primary outcomes were scores on the Paediatric Symptom Checklist (PSC; internalising, externalising, and attentional difficulty scales) assessed at week 0, 9 weeks, and 3 months after treatment (primary outcome time point). It was hypothesised that EASE would result in greater reductions on internalising symptoms than EUC. Secondary outcomes were depression, posttraumatic stress, well-being, functioning, school belongingness, and caregivers’ parenting and mental health. Between June 2019 and January 2020, 1,842 young adolescent refugees were screened for eligibility on the basis of psychological distress. There were 520 adolescents (28.2%) who screened positive, of whom 471 (90.6%) agreed to enter the trial. Overall, 185 were assigned to EASE and 286 to EUC, and 169 and 254 were retained at 3 months for EASE and EUC, respectively. Intent-to-treat analyses indicated that at 3 months, EASE resulted in greater reduction on the PSC-internalising scale than EUC (estimated mean difference 0.69, 95% CI 0.19 to 1.19; p = 0.007; effect size, 0.38) but there were no differences for PSC-externalising (estimated mean difference 0.24, 95% CI −0.43 to 0.91; p = 0.49; effect size, −0.10), PSC-attentional problem (estimated mean difference −0.01, 95% CI −0.51 to 0.54; p = 0.97; effect size, −0.01) scores, or on depression, posttraumatic stress, well-being, functioning, or school belongingness. Relative to EUC, caregivers in EASE had less psychological distress (estimated mean difference 1.95, 95% CI 0.71 to 3.19; p = 0.002) and inconsistent disciplinary parenting (mean difference 1.54, 95% CI 1.03 to 2.05; p < 0.001). Secondary analyses that (a) focused on adolescents with probable internalising disorders; (b) completed the 3-month assessment; and (c) controlled for trauma exposure did not alter the primary results. Mediation analysis indicated that for caregivers in the EASE condition, reduction in inconsistent disciplinary parenting was associated with reduced attentional (β = 0.11, SE 0.07; 95% CI 0.003, 0.274) and internalising (β = 0.11, SE 0.07; 95% CI 0.003, 0.274) problems in their children. No adverse events were attributable to the intervention. A limitation was that EUC was not matched to EASE in terms of facilitator attention or group involvement.ConclusionsEASE led to reduced internalising problems in young refugee adolescents and was associated with reduced distress and less inconsistent disciplinary parenting in caregivers. This intervention has the potential as a scalable intervention to mitigate young adolescents’ emotional difficulties in LMIC.Trial registrationProspectively registered at Australian and New Zealand Clinical Trials Registry: ACTRN12619000341123.

In a randomized controlled trial, Richard A. Bryant and colleagues study the effectiveness of the Early Adolescent Skills for Emotions (EASE) intervention to improve the mental health of Syrian refugees aged 10-14 years living in Jordan.     

Evaluation of an adapted version of the Diabetes Prevention Program for low- and middle-income countries: A cluster randomized trial to evaluate “Lifestyle Africa” in South Africa

BackgroundLow- and middle-income countries (LMICs) are experiencing major increases in diabetes and cardiovascular conditions linked to overweight and obesity. Lifestyle interventions such as the United States National Diabetes Prevention Program (DPP) developed in high-income countries require adaptation and cultural tailoring for LMICs. The objective of this study was to evaluate the efficacy of “Lifestyle Africa,” an adapted version of the DPP tailored for an underresourced community in South Africa compared to usual care.Methods and findingsParticipants were residents of a predominantly Xhosa-speaking urban township of Cape Town, South Africa characterized by high rates of poverty. Participants with body mass index (BMI) ≥ 25 kg/m² who were members of existing social support groups or “clubs” receiving health services from local nongovernmental organizations (NGOs) were enrolled in a cluster randomized controlled trial that compared Lifestyle Africa (the intervention condition) to usual care (the control condition). The Lifestyle Africa intervention consisted of 17 video-based group sessions delivered by trained community health workers (CHWs). Clusters were randomized using a numbered list of the CHWs and their assigned clubs based on a computer-based random allocation scheme. CHWs, participants, and research team members could not be blinded to condition. Percentage weight loss (primary outcome), hemoglobin A1c (HbA1c), blood pressure, triglycerides, and low-density lipoprotein (LDL) cholesterol were assessed 7 to 9 months after enrollment. An individual-level intention-to-treat analysis was conducted adjusting for clustering within clubs and baseline values. Trial registration is at ClinicalTrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT03342274","term_id":"NCT03342274"}}NCT03342274). Between February 2018 and May 2019, 782 individuals were screened, and 494 were enrolled. Participants were predominantly retired (57% were receiving a pension) and female (89%) with a mean age of 68 years. Participants from 28 clusters were allocated to Lifestyle Africa (15, n = 240) or usual care (13, n = 254). Fidelity assessments indicated that the intervention was generally delivered as intended. The modal number of sessions held across all clubs was 17, and the mean attendance of participants across all sessions was 61%. Outcome assessment was completed by 215 (90%) intervention and 223 (88%) control participants. Intent-to-treat analyses utilizing multilevel modeling included all randomized participants. Mean weight change (primary outcome) was −0.61% (95% confidence interval (CI) = −1.22, −0.01) in Lifestyle Africa and −0.44% (95% CI = −1.06, 0.18) in control with no significant difference (group difference = −0.17%; 95% CI = −1.04, 0.71; p = 0.71). However, HbA1c was significantly lower at follow-up in Lifestyle Africa compared to the usual care group (mean difference = −0.24, 95% CI = −0.39, −0.09, p = 0.001). None of the other secondary outcomes differed at follow-up: systolic blood pressure (group difference = −1.36; 95% CI = −6.92, 4.21; p = 0.63), diastolic blood pressure (group difference = −0.39; 95% CI = −3.25, 2.30; p = 0.78), LDL (group difference = −0.07; 95% CI = −0.19, 0.05; p = 0.26), triglycerides (group difference = −0.02; 95% CI = −0.20, 0.16; p = 0.80). There were no unanticipated problems and serious adverse events were rare, unrelated to the intervention, and similar across groups (11 in Lifestyle Africa versus 13 in usual care). Limitations of the study include the lack of a rigorous dietary intake measure and the high representation of older women.ConclusionsIn this study, we found that Lifestyle Africa was feasible for CHWs to deliver and, although it had no effect on the primary outcome of weight loss or secondary outcomes of blood pressure or triglycerides, it had an apparent small significant effect on HbA1c. The study demonstrates the potential feasibility of CHWs to deliver a program without expert involvement by utilizing video-based sessions. The intervention may hold promise for addressing cardiovascular disease (CVD) and diabetes at scale in LMICs.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03342274","term_id":"NCT03342274"}}NCT03342274.

In a cluster randomized trial, Delwyn Catley and colleagues evaluate an adapted version of the Diabetes Prevention Program in South Africa.     

Importance of attributes and willingness to pay for oral anticoagulant therapy in patients with atrial fibrillation in China: A discrete choice experiment

BackgroundAdherence to oral anticoagulant therapy in patients with atrial fibrillation (AF) in China is low. Patient preference, one of the main reasons for discontinuation of oral anticoagulant therapy, is an unfamiliar concept in China.Methods and findingsA discrete choice experiment (DCE) was conducted to quantify patient preference on 7 attributes of oral anticoagulant therapy: antidote (yes/no), food–drug interaction (yes/no), frequency of blood monitoring (no need, every 6/3/1 month[s]), risk of nonfatal major bleeding (0.7/3.1/5.5/7.8[%]), risk of nonfatal stroke (ischemic/hemorrhagic) or systemic embolism (0.6/3.2/5.8/8.4[%]), risk of nonfatal acute myocardial infarction (AMI) (0.2/1.0/1.8/2.5[%]), and monthly out-of-pocket cost (0/120/240/360 RMB) (0 to 56 USD). A total of 16 scenarios were generated by using D-Efficient design and were randomly divided into 2 blocks. Eligible patients were recruited and interviewed from outpatient and inpatient settings of 2 public hospitals in Beijing and Shenzhen, respectively. Patients were presented with 8 scenarios and asked to select 1 of 3 options: 2 unlabeled hypothetical treatments and 1 opt-out option. Mixed logit regression model was used for estimating patients’ preferences of attributes of oral anticoagulants and willingness to pay (WTP) with adjustments for age, sex, education level, income level, city, self-evaluated health score, histories of cardiovascular disease/other vascular disease/any stroke/any bleeding, and use of anticoagulant/antiplatelet therapy. A total of 506 patients were recruited between May 2018 and December 2019 (mean age 70.3 years, 42.1% women). Patients were mainly concerned about the risks of AMI (β: −1.03; 95% CI: −1.31, −0.75; p < 0.001), stroke or systemic embolism (β: −0.81; 95% CI: −0.90, −0.73; p < 0.001), and major bleeding (β: −0.69; 95% CI: −0.78, −0.60; p < 0.001) and were willing to pay more, from up to 798 RMB to 536 RMB (124 to 83 USD) monthly. The least concerning attribute was frequency of blood monitoring (β: −0.31; 95% CI: −0.39, −0.24; p < 0.001). Patients had more concerns about food–drug interactions even exceeding preferences on the 3 risks, if they had a history of stroke or bleeding (β: −2.47; 95% CI: −3.92, −1.02; p < 0.001), recruited from Beijing (β: −1.82; 95% CI: −2.56, −1.07; p < 0.001), or men (β: −0.96; 95% CI: −1.36, −0.56; p < 0.001). Patients with lower educational attainment or lower income weighted all attributes lower, and their WTP for incremental efficacy and safety was minimal. Since the patients were recruited from 2 major hospitals from developed cities in China, further studies with better representative samples would be needed.ConclusionsPatients with AF in China were mainly concerned about the safety and effectiveness of oral anticoagulant therapy. The preference weighting on food–drug interaction varied widely. Patients with lower educational attainment or income levels and less experience of bleeding or stroke had more reservations about paying for oral anticoagulant therapies with superior efficacy, safety, and convenience of use.

In a discrete choice experiment, Jiaxi Zhao and colleagues investigate the importance of attributes of oral anticoagulant therapy and willingness-to-pay in patients with atrial fibrillation in China.     

Racial Discrimination & Cardiovascular Disease Risk: My Body My Story Study of 1005 US-Born Black and White Community Health Center Participants (US)

Objectives

To date, limited and inconsistent evidence exists regarding racial discrimination and risk of cardiovascular disease (CVD).

Methods

Cross-sectional observational study of 1005 US-born non-Hispanic black (n = 504) and white (n = 501) participants age 35–64 randomly selected from community health centers in Boston, MA (2008–2010; 82.4% response rate), using 3 racial discrimination measures: explicit self-report; implicit association test (IAT, a time reaction test for self and group as target vs. perpetrator of discrimination); and structural (Jim Crow status of state of birth, i.e. legal racial discrimination prior 1964).

Results

Black and white participants both had adverse cardiovascular and socioeconomic profiles, with black participants most highly exposed to racial discrimination. Positive crude associations among black participants occurred for Jim Crow birthplace and hypertension (odds ratio (OR) 1.92, 95% confidence interval (CI) 1.28, 2.89) and for explicit self-report and the Framingham 10 year CVD risk score (beta  = 0.04; 95% CI 0.01, 0.07); among white participants, only negative crude associations existed (for IAT for self, for lower systolic blood pressure (SBP; beta  = −4.86; 95% CI −9.08, −0.64) and lower Framingham CVD score (beta  = −0.36, 95% CI −0.63, −0.08)). All of these associations were attenuated and all but the white IAT-Framingham risk score association were rendered null in analyses that controlled for lifetime socioeconomic position and additional covariates. Controlling for racial discrimination, socioeconomic position, and other covariates did not attenuate the crude black excess risk for SBP and hypertension and left unaffected the null excess risk for the Framingham CVD score.

Conclusion

Despite worse exposures among the black participants, racial discrimination and socioeconomic position were not associated, in multivariable analyses, with risk of CVD. We interpret results in relation to constrained variability of exposures and outcomes and discuss implications for valid research on social determinants of health.     

Effectiveness of a primary care-based integrated mobile health intervention for stroke management in rural China (SINEMA): A cluster-randomized controlled trial

BackgroundManaging noncommunicable diseases through primary healthcare has been identified as the key strategy to achieve universal health coverage but is challenging in most low- and middle-income countries. Stroke is the leading cause of death and disability in rural China. This study aims to determine whether a primary care-based integrated mobile health intervention (SINEMA intervention) could improve stroke management in rural China.Methods and findingsBased on extensive barrier analyses, contextual research, and feasibility studies, we conducted a community-based, two-arm cluster-randomized controlled trial with blinded outcome assessment in Hebei Province, rural Northern China including 1,299 stroke patients (mean age: 65.7 [SD:8.2], 42.6% females, 71.2% received education below primary school) recruited from 50 villages between June 23 and July 21, 2017. Villages were randomly assigned (1:1) to either the intervention or control arm (usual care). In the intervention arm, village doctors who were government-sponsored primary healthcare providers received training, conducted monthly follow-up visits supported by an Android-based mobile application, and received performance-based payments. Participants received monthly doctor visits and automatically dispatched daily voice messages. The primary outcome was the 12-month change in systolic blood pressure (BP). Secondary outcomes were predefined, including diastolic BP, health-related quality of life, physical activity level, self-reported medication adherence (antiplatelet, statin, and antihypertensive), and performance in “timed up and go” test. Analyses were conducted in the intention-to-treat framework at the individual level with clusters and stratified design accounted for by following the prepublished statistical analysis plan. All villages completed the 12-month follow-up, and 611 (intervention) and 615 (control) patients were successfully followed (3.4% lost to follow-up among survivors). The program was implemented with high fidelity, and the annual program delivery cost per capita was US$24.3. There was a significant reduction in systolic BP in the intervention as compared with the control group with an adjusted mean difference: −2.8 mm Hg (95% CI −4.8, −0.9; p = 0.005). The intervention was significantly associated with improvements in 6 out of 7 secondary outcomes in diastolic BP reduction (p < 0.001), health-related quality of life (p = 0.008), physical activity level (p < 0.001), adherence in statin (p = 0.003) and antihypertensive medicines (p = 0.039), and performance in “timed up and go” test (p = 0.022). We observed reductions in all exploratory outcomes, including stroke recurrence (4.4% versus 9.3%; risk ratio [RR] = 0.46, 95% CI 0.32, 0.66; risk difference [RD] = 4.9 percentage points [pp]), hospitalization (4.4% versus 9.3%; RR = 0.45, 95% CI 0.32, 0.62; RD = 4.9 pp), disability (20.9% versus 30.2%; RR = 0.65, 95% CI 0.53, 0.79; RD = 9.3 pp), and death (1.8% versus 3.1%; RR = 0.52, 95% CI 0.28, 0.96; RD = 1.3 pp). Limitations include the relatively short study duration of only 1 year and the generalizability of our findings beyond the study setting.ConclusionsIn this study, a primary care-based mobile health intervention integrating provider-centered and patient-facing technology was effective in reducing BP and improving stroke secondary prevention in a resource-limited rural setting in China.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03185858","term_id":"NCT03185858"}}NCT03185858.

Lijing Yan and colleagues evaluate a mobile health intervention for secondary stroke prevention in China.     

Brain-based measures of nociception during general anesthesia with remifentanil: A randomized controlled trial

BackgroundCatheter radiofrequency (RF) ablation for cardiac arrhythmias is a painful procedure. Prior work using functional near-infrared spectroscopy (fNIRS) in patients under general anesthesia has indicated that ablation results in activity in pain-related cortical regions, presumably due to inadequate blockade of afferent nociceptors originating within the cardiac system. Having an objective brain-based measure for nociception and analgesia may in the future allow for enhanced analgesic control during surgical procedures. Hence, the primary aim of this study is to demonstrate that the administration of remifentanil, an opioid widely used during surgery, can attenuate the fNIRS cortical responses to cardiac ablation.Methods and findingsWe investigated the effects of continuous remifentanil on cortical hemodynamics during cardiac ablation under anesthesia. In a randomized, double-blinded, placebo (PL)-controlled trial, we examined 32 pediatric patients (mean age of 15.8 years,16 females) undergoing catheter ablation for cardiac arrhythmias at the Cardiology Department of Boston Children’s Hospital from October 2016 to March 2020; 9 received 0.9% NaCl, 12 received low-dose (LD) remifentanil (0.25 mcg/kg/min), and 11 received high-dose (HD) remifentanil (0.5 mcg/kg/min). The hemodynamic changes of primary somatosensory and prefrontal cortices were recorded during surgery using a continuous wave fNIRS system. The primary outcome measures were the changes in oxyhemoglobin concentration (Nadir_HbO, i.e., lowest oxyhemoglobin concentration and Peak_HbO, i.e., peak change and area under the curve) of medial frontopolar cortex (mFPC), lateral prefrontal cortex (lPFC) and primary somatosensory cortex (S1) to ablation in PL versus remifentanil groups. Secondary measures included the fNIRS response to an auditory control condition. The data analysis was performed on an intention-to-treat (ITT) basis. Remifentanil group (dosage subgroups combined) was compared with PL, and a post hoc analysis was performed to identify dose effects. There were no adverse events. The groups were comparable in age, sex, and number of ablations. Results comparing remifentanil versus PL show that PL group exhibit greater Nadir_HbO in inferior mFPC (mean difference (MD) = 1.229, 95% confidence interval [CI] = 0.334, 2.124, p < 0.001) and superior mFPC (MD = 1.206, 95% CI = 0.303, 2.109, p = 0.001) and greater Peak_HbO in inferior mFPC (MD = −1.138, 95% CI = −2.062, −0.214, p = 0.002) and superior mFPC (MD = −0.999, 95% CI = −1.961, −0.036, p = 0.008) in response to ablation. S1 activation from ablation was greatest in PL, then LD, and HD groups, but failed to reach significance, whereas lPFC activation to ablation was similar in all groups. Ablation versus auditory stimuli resulted in higher Peak_HbO in inferior mFPC (MD = 0.053, 95% CI = 0.004, 0.101, p = 0.004) and superior mFPC (MD = 0.052, 95% CI = 0.013, 0.091, p < 0.001) and higher Nadir_HbO in posterior superior S1 (Pos. SS1; MD = −0.342, 95% CI = −0.680, −0.004, p = 0.007) during ablation of all patients. Remifentanil group had smaller Nadir_HbO in inferior mFPC (MD = 0.098, 95% CI = 0.009, 0.130, p = 0.003) and superior mFPC (MD = 0.096, 95% CI = 0.008, 0.116, p = 0.003) and smaller Peak_HbO in superior mFPC (MD = −0.092, 95% CI = −0.680, −0.004, p = 0.007) during both the stimuli. Study limitations were small sample size, motion from surgery, indirect measure of nociception, and shallow penetration depth of fNIRS only allowing access to superficial cortical layers.ConclusionsWe observed cortical activity related to nociception during cardiac ablation under general anesthesia with remifentanil. It highlights the potential of fNIRS to provide an objective pain measure in unconscious patients, where cortical-based measures may be more accurate than current evaluation methods. Future research may expand on this application to produce a real-time indication of pain that will aid clinicians in providing immediate and adequate pain treatment.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02703090","term_id":"NCT02703090"}}NCT02703090

In a randomized controlled trial, Keerthana Karunakaran, Barry Kussman, and colleagues study whether remifentanil attenuates pain-related brain activity during cardiac ablation surgery.     

Comparative effect of physical exercise versus statins on improving arterial stiffness in patients with high cardiometabolic risk: A network meta-analysis

BackgroundThe comparative analysis of the effect of several doses of statins against different intensities of physical exercise on arterial stiffness (a measure of cardiovascular risk) could shed light for clinicians on which method is most effective in preventing cardiovascular disease (CVD) and be used to inform shared decision-making between doctors and patients. This study was aimed at analyzing the effect, in high cardiometabolic risk patients, of different statins doses and exercise intensities on arterial stiffness (a measure of cardiovascular risk) by integrating all available direct and indirect evidence in network meta-analyses.Methods and findingsWe systematically searched MEDLINE, Embase, SPORTDiscus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science databases from their inception to February 28, 2020; for unpublished trials, we also searched ClinicalTrials.gov. We searched for studies concerning the effect of statins or physical exercise on arterial stiffness, measured by pulse wave velocity (PWV). For methodological quality assessment, Cochrane Collaboration’s tool for assessing risk of bias (RoB2) was used. A network geometry graph was used to assess the strength of the evidence. Comparative evaluation of the interventions effect was performed by conducting a standard pairwise meta-analysis and a network meta-analysis (NMA) for direct and indirect comparisons between interventions and control/nonintervention. A total of 22 studies were included in the analyses (18 randomized controlled trials (RCTs) and 4 nonrandomized experimental studies), including 1,307 patients with high cardiometabolic risk from Asia (3 studies), Oceania (2 studies), Europe (10 studies), North America (5 studies), and South America (2 studies). The overall risk of bias assessed with RoB2 was high in all included studies. For standard pairwise meta-analysis and NMA, high-intensity exercise versus control (mean difference (MD) −0.56; 95% CI: −1.01, −0.11; p = 0.015 and −0.62; 95% CI: −1.20, −0.04; p = 0.038, respectively) and moderate statin dose versus control (MD −0.80, 95% CI: −1.59, −0.01; p = 0.048 and −0.73, 95% CI: −1.30, −0.15; p = 0.014, respectively) showed significant MDs. When nonrandomized experimental studies were excluded, the effect on high-intensity exercise versus control and moderate statin dose versus was slightly modified. The main limitation of this study was that the magnitude of the effect of the exercise interventions could be underestimated due to regression toward the mean bias because the baseline cardiometabolic risk profile of patients in the physical exercise intervention trials was healthier than those in the statins ones; consequently, more modest improvements in physical exercise interventions compared to statins interventions can be expected. Additionally, we might consider as limitations the small study sizes, the heterogeneous patient groups, the focus on a proxy endpoint (PWV), and the high risk of bias.ConclusionsIn this NMA, we found that although many patients could benefit from statins for reducing CVD risk, our results support that, considering the beneficial effects of high-intensity exercise on arterial stiffness, it would be worthwhile to refocus our attention on this type of exercise as an effective tool for the prevention of CVD.Systematic review registrationPROSPERO CRD42019123120.

In this network meta-analysis, Iván Cavero-Redondo and colleagues synthesise findings on statins vs. exercise for alleviating arterial stiffness.     

Epidemiology and management of gout in Taiwan: a nationwide population study

IntroductionGout is the most common inflammatory arthritis worldwide and is the only type of chronic arthritis that potentially can be ‘cured’. However, data on gout incidence, prevalence and management, assessed at multiple time points in the same population, are sparse, particularly in Asian populations. The aim of this study was to describe trends in the epidemiology of gout in the general population of Taiwan.MethodsThe National Health Insurance Research Database was used to identify patients with gout and to estimate the prevalence and incidence of gout for each calendar year from 2005 to 2010. The pattern of gout management was also examined.ResultsOf 23,371,362 beneficiaries in 2010, there were 1,458,569 prevalent and 56,595 incident cases of gout, giving a prevalence of 6.24% (95% confidence interval (CI), 6.23% to 6.25%) and an incidence of 2.74 (95% CI, 2.72 to 2.76) per 1,000 person-years. The annual percentage change (APC) of the standardised prevalence was −0.7% (95% CI, −1.7% to 0.3%; P = 0.14), suggesting that the prevalence of gout was essentially the same throughout the study period. However, The APC of incidence was −13.4 (95% CI, −16.1 to −10.6) between 2005 and 2007 and −2.1 (95% CI, −10.4 to 7.1) between 2007 and 2010. Regions with the highest prevalence and incidence were eastern coastal counties and offshore islets, where indigenous people are clustered. Among prevalent gout cases in 2010, only 22.93% (95% CI, 22.87% to 23.00%) were prescribed urate-lowering treatment (ULT), which remained unchanged between 2005 and 2010 at an APC of 0.0 (95% CI, −3.8 to 4.0). Uricosuric agents were more commonly prescribed than xanthine oxidase inhibitors in Taiwan.ConclusionsIn Taiwan, 1 in 16 people have gout. Whereas the incidence has decreased recently, the prevalence remains unchanged. Management of gout in Taiwan is poor, with only one in five affected people being treated with ULT.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0522-8) contains supplementary material, which is available to authorized users.     

Conflict violence reduction and pregnancy outcomes: A regression discontinuity design in Colombia

BackgroundThe relationship between exposure to conflict violence during pregnancy and the risks of miscarriage, stillbirth, and perinatal mortality has not been studied empirically using rigorous methods and appropriate data. We investigated the association between reduced exposure to conflict violence during pregnancy and the risks of adverse pregnancy outcomes in Colombia.Methods and findingsWe adopted a regression discontinuity (RD) design using the July 20, 2015 cease-fire declared during the Colombian peace process as an exogenous discontinuous change in exposure to conflict events during pregnancy, comparing women with conception dates before and after the cease-fire date. We constructed the cohorts of all pregnant women in Colombia for each day between January 1, 2013 and December 31, 2017 using birth and death certificates. A total of 3,254,696 women were followed until the end of pregnancy. We measured conflict exposure as the total number of conflict events that occurred in the municipality where a pregnant woman lived during her pregnancy. We first assessed whether the cease-fire did induce a discontinuous fall in conflict exposure for women with conception dates after the cease-fire to then estimate the association of this reduced exposure with the risks of miscarriage, stillbirth, and perinatal mortality. We found that the July 20, 2015 cease-fire was associated with a reduction of the average number of conflict events (from 2.64 to 2.40) to which women were exposed during pregnancy in their municipalities of residence (mean differences −0.24; 95% confidence interval [CI] −0.35 to −0.13; p < 0.001). This association was greater in municipalities where Fuerzas Armadas Revolucionarias de Colombia (FARC) had a greater presence historically. The reduction in average exposure to conflict violence was, in turn, associated with a decrease of 9.53 stillbirths per 1,000 pregnancies (95% CI −16.13 to −2.93; p = 0.005) for municipalities with total number of FARC-related violent events above the 90th percentile of the distribution of FARC-related conflict events and a decrease of 7.57 stillbirths per 1,000 pregnancies (95% CI −13.14 to −2.00; p = 0.01) for municipalities with total number of FARC-related violent events above the 75th percentile of FARC-related events. For perinatal mortality, we found associated reductions of 10.69 (95% CI −18.32 to −3.05; p = 0.01) and 6.86 (95% CI −13.24 to −0.48; p = 0.04) deaths per 1,000 pregnancies for the 2 types of municipalities, respectively. We found no association with miscarriages. Formal tests support the validity of the key RD assumptions in our data, while a battery of sensitivity analyses and falsification tests confirm the robustness of our empirical results. The main limitations of the study are the retrospective nature of the information sources and the potential for conflict exposure misclassification.ConclusionsOur study offers evidence that reduced exposure to conflict violence during pregnancy is associated with important (previously unmeasured) benefits in terms of reducing the risk of stillbirth and perinatal deaths. The findings are consistent with such beneficial associations manifesting themselves mainly through reduced violence exposure during the early stages of pregnancy. Beyond the relevance of this evidence for other countries beset by chronic armed conflicts, our results suggest that the fledgling Colombian peace process may be already contributing to better population health.

Using a regression discontinuity design, Giancarlo Buitrago and co-authors investigate the impact of conflict violence reduction on pregnancy outcomes in Colombia from 2013-2017.     

Effectiveness and costs associated with a lay counselor–delivered,brief problem-solving mental health intervention for adolescents in urban,low-income schools in India: 12-month outcomes of a randomized controlled trial

BackgroundPsychosocial interventions for adolescent mental health problems are effective, but evidence on their longer-term outcomes is scarce, especially in low-resource settings. We report on the 12-month sustained effectiveness and costs of scaling up a lay counselor–delivered, transdiagnostic problem-solving intervention for common adolescent mental health problems in low-income schools in New Delhi, India.Methods and findingsParticipants in the original trial were 250 school-going adolescents (mean [M] age = 15.61 years, standard deviation [SD] = 1.68), including 174 (69.6%) who identified as male. Participants were recruited from 6 government schools over a period of 4 months (August 20 to December 14, 2018) and were selected on the basis of elevated mental health symptoms and distress/functional impairment. A 2-arm, randomized controlled trial design was used to examine the effectiveness of a lay counselor–delivered, problem-solving intervention (4 to 5 sessions over 3 weeks) with supporting printed booklets (intervention arm) in comparison with problem solving delivered via printed booklets alone (control arm), at the original endpoints of 6 and 12 weeks. The protocol was modified, as per the recommendation of the Trial Steering Committee, to include a post hoc extension of the follow-up period to 12 months. Primary outcomes were adolescent-reported psychosocial problems (Youth Top Problems [YTP]) and mental health symptoms (Strengths and Difficulties Questionnaire [SDQ] Total Difficulties scale). Other self-reported outcomes included SDQ subscales, perceived stress, well-being, and remission. The sustained effects of the intervention were estimated at the 12-month endpoint and over 12 months (the latter assumed a constant effect across 3 follow-up points) using a linear mixed model for repeated measures and involving complete case analysis. Sensitivity analyses examined the effect of missing data using multiple imputations. Costs were estimated for delivering the intervention during the trial and from modeling a scale-up scenario, using a retrospective ingredients approach. Out of the 250 original trial participants, 176 (70.4%) adolescents participated in the 12-month follow-up assessment. One adverse event was identified during follow-up and deemed unrelated to the intervention. Evidence was found for intervention effects on both SDQ Total Difficulties and YTP at 12 months (YTP: adjusted mean difference [AMD] = −0.75, 95% confidence interval [CI] = −1.47, −0.03, p = 0.04; SDQ Total Difficulties: AMD = −1.73, 95% CI = −3.47, 0.02, p = 0.05), with stronger effects over 12 months (YTP: AMD = −0.98, 95% CI = −1.51, −0.45, p < 0.001; SDQ Total Difficulties: AMD = −1.23, 95% CI = −2.37, −0.09; p = 0.03). There was also evidence for intervention effects on internalizing symptoms, impairment, perceived stress, and well-being over 12 months. The intervention effect was stable for most outcomes on sensitivity analyses adjusting for missing data; however, for SDQ Total Difficulties and impairment, the effect was slightly attenuated. The per-student cost of delivering the intervention during the trial was $3 United States dollars (USD; or $158 USD per case) and for scaling up the intervention in the modeled scenario was $4 USD (or $23 USD per case). The scaling up cost accounted for 0.4% of the per-student school budget in New Delhi. The main limitations of the study’s methodology were the lack of sample size calculations powered for 12-month follow-up and the absence of cost-effectiveness analyses using the primary outcomes.ConclusionsIn this study, we observed that a lay counselor–delivered, brief transdiagnostic problem-solving intervention had sustained effects on psychosocial problems and mental health symptoms over the 12-month follow-up period. Scaling up this resource-efficient intervention is an affordable policy goal for improving adolescents’ access to mental health care in low-resource settings. The findings need to be interpreted with caution, as this study was a post hoc extension, and thus, the sample size calculations did not take into account the relatively high attrition rate observed during the long-term follow-up.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03630471","term_id":"NCT03630471"}}NCT03630471.

Kanika Malik, Daniel Michelson, and colleagues study the sustained effectiveness of a lay counsellor-delivered problem solving intervention to mental health of adolescents enrolled in low-income schools in New Delhi, India.     

Induction of labour at 41 weeks or expectant management until 42 weeks: A systematic review and an individual participant data meta-analysis of randomised trials

BackgroundThe risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an individual participant data meta-analysis (IPD-MA) on this subject.Methods and findingsWe searched PubMed, Excerpta Medica dataBASE (Embase), The Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and PsycINFO on February 21, 2020 for RCTs comparing IOL at 41 weeks with expectant management until 42 weeks in women with uncomplicated pregnancies. Individual participant data (IPD) were sought from eligible RCTs. Primary outcome was a composite of severe adverse perinatal outcomes: mortality and severe neonatal morbidity. Additional outcomes included neonatal admission, mode of delivery, perineal lacerations, and postpartum haemorrhage. Prespecified subgroup analyses were conducted for parity (nulliparous/multiparous), maternal age (<35/≥35 years), and body mass index (BMI) (<30/≥30). Aggregate data meta-analysis (MA) was performed to include data from RCTs for which IPD was not available.From 89 full-text articles, we identified three eligible RCTs (n = 5,161), and two contributed with IPD (n = 4,561). Baseline characteristics were similar between the groups regarding age, parity, BMI, and higher level of education. IOL resulted overall in a decrease of severe adverse perinatal outcome (0.4% [10/2,281] versus 1.0% [23/2,280]; relative risk [RR] 0.43 [95% confidence interval [CI] 0.21 to 0.91], p-value 0.027, risk difference [RD] −57/10,000 [95% CI −106/10,000 to −8/10,000], I² 0%). The number needed to treat (NNT) was 175 (95% CI 94 to 1,267).Perinatal deaths occurred in one (<0.1%) versus eight (0.4%) pregnancies (Peto odds ratio [OR] 0.21 [95% CI 0.06 to 0.78], p-value 0.019, RD −31/10,000, [95% CI −56/10,000 to −5/10,000], I² 0%, NNT 326, [95% CI 177 to 2,014]) and admission to a neonatal care unit ≥4 days occurred in 1.1% (24/2,280) versus 1.9% (46/2,273), (RR 0.52 [95% CI 0.32 to 0.85], p-value 0.009, RD −97/10,000 [95% CI −169/10,000 to −26/10,000], I² 0%, NNT 103 [95% CI 59 to 385]). There was no difference in the rate of cesarean delivery (10.5% versus 10.7%; RR 0.98, [95% CI 0.83 to 1.16], p-value 0.81) nor in other important perinatal, delivery, and maternal outcomes. MA on aggregate data showed similar results.Prespecified subgroup analyses for the primary outcome showed a significant difference in the treatment effect (p = 0.01 for interaction) for parity, but not for maternal age or BMI. The risk of severe adverse perinatal outcome was decreased for nulliparous women in the IOL group (0.3% [4/1,219] versus 1.6% [20/1,264]; RR 0.20 [95% CI 0.07 to 0.60], p-value 0.004, RD −127/10,000, [95% CI −204/10,000 to −50/10,000], I² 0%, NNT 79 [95% CI 49 to 201]) but not for multiparous women (0.6% [6/1,219] versus 0.3% [3/1,264]; RR 1.59 [95% CI 0.15 to 17.30], p-value 0.35, RD 27/10,000, [95% CI −29/10,000 to 84/10,000], I² 55%).A limitation of this IPD-MA was the risk of overestimation of the effect on perinatal mortality due to early stopping of the largest included trial for safety reasons after the advice of the Data and Safety Monitoring Board. Furthermore, only two RCTs were eligible for the IPD-MA; thus, the possibility to assess severe adverse neonatal outcomes with few events was limited.ConclusionsIn this study, we found that, overall, IOL at 41 weeks improved perinatal outcome compared with expectant management until 42 weeks without increasing the cesarean delivery rate. This benefit is shown only in nulliparous women, whereas for multiparous women, the incidence of mortality and morbidity was too low to demonstrate any effect. The magnitude of risk reduction of perinatal mortality remains uncertain. Women with pregnancies approaching 41 weeks should be informed on the risk differences according to parity so that they are able to make an informed choice for IOL at 41 weeks or expectant management until 42 weeks.Study Registration: PROSPERO CRD42020163174

Mårten Alkmark and co-workers report on a meta-analysis of randomized trials of labour induction at 41 weeks'' gestation as compared with expectant management until 42 weeks.     

Genetic associations with temporal shifts in obesity and severe obesity during the obesity epidemic in Norway: A longitudinal population-based cohort (the HUNT Study)

BackgroundObesity has tripled worldwide since 1975 as environments are becoming more obesogenic. Our study investigates how changes in population weight and obesity over time are associated with genetic predisposition in the context of an obesogenic environment over 6 decades and examines the robustness of the findings using sibling design.Methods and findingsA total of 67,110 individuals aged 13–80 years in the Nord-Trøndelag region of Norway participated with repeated standardized body mass index (BMI) measurements from 1966 to 2019 and were genotyped in a longitudinal population-based health study, the Trøndelag Health Study (the HUNT Study). Genotyping required survival to and participation in the HUNT Study in the 1990s or 2000s. Linear mixed models with observations nested within individuals were used to model the association between a genome-wide polygenic score (GPS) for BMI and BMI, while generalized estimating equations were used for obesity (BMI ≥ 30 kg/m²) and severe obesity (BMI ≥ 35 kg/m²).The increase in the average BMI and prevalence of obesity was steeper among the genetically predisposed. Among 35-year-old men, the prevalence of obesity for the least predisposed tenth increased from 0.9% (95% confidence interval [CI] 0.6% to 1.2%) to 6.5% (95% CI 5.0% to 8.0%), while the most predisposed tenth increased from 14.2% (95% CI 12.6% to 15.7%) to 39.6% (95% CI 36.1% to 43.0%). Equivalently for women of the same age, the prevalence of obesity for the least predisposed tenth increased from 1.1% (95% CI 0.7% to1.5%) to 7.6% (95% CI 6.0% to 9.2%), while the most predisposed tenth increased from 15.4% (95% CI 13.7% to 17.2%) to 42.0% (95% CI 38.7% to 45.4%). Thus, for 35-year-old men and women, respectively, the absolute change in the prevalence of obesity from 1966 to 2019 was 19.8 percentage points (95% CI 16.2 to 23.5, p < 0.0001) and 20.0 percentage points (95% CI 16.4 to 23.7, p < 0.0001) greater for the most predisposed tenth compared with the least predisposed tenth, defined using the GPS for BMI. The corresponding absolute changes in the prevalence of severe obesity for men and women, respectively, were 8.5 percentage points (95% CI 6.3 to 10.7, p < 0.0001) and 12.6 percentage points (95% CI 9.6 to 15.6, p < 0.0001) greater for the most predisposed tenth. The greater increase in BMI in genetically predisposed individuals over time was apparent after adjustment for family-level confounding using a sibling design. Key limitations include a slightly lower survival to date of genetic testing for the older cohorts and that we apply a contemporary genetic score to past time periods. Future research should validate our findings using a polygenic risk score constructed from historical data.ConclusionsIn the context of increasingly obesogenic changes in our environment over 6 decades, our findings reveal a growing inequality in the risk for obesity and severe obesity across GPS tenths. Our results suggest that while obesity is a partially heritable trait, it is still modifiable by environmental factors. While it may be possible to identify those most susceptible to environmental change, who thus have the most to gain from preventive measures, efforts to reverse the obesogenic environment will benefit the whole population and help resolve the obesity epidemic.

In a longitudinal population-based cohort study in Norway, Maria Brandkvist and colleagues investigate how genetic predisposition relates to changes in BMI and obesity over the past six decades.     

School performance in Danish children exposed to maternal type 1 diabetes in utero: A nationwide retrospective cohort study

BackgroundConflicting results have been reported concerning possible adverse effects on the cognitive function of offspring of mothers with type 1 diabetes (O-mT1D). Previous studies have included offspring of parents from the background population (O-BP), but not offspring of fathers with type 1 diabetes (O-fT1D) as the unexposed reference group.Methods and findingsThis is a population-based retrospective cohort study from 2010 to 2016. Nationally standardized school test scores (range, 1 to 100) were obtained for public school grades 2, 3, 4, 6, and 8 in O-mT1D and compared with those in O-fT1D and O-BP. Of the 622,073 included children, 2,144 were O-mT1D, and 3,474 were O-fT1D. Multiple linear regression models were used to compare outcomes, including the covariates offspring with type 1 diabetes, parity, number of siblings, offspring sex, smoking during pregnancy, parental age, and socioeconomic factors. Mean test scores were 54.2 (standard deviation, SD 24.8) in O-mT1D, 54.4 (SD 24.8) in O-fT1D, and 56.4 (SD 24.7) in O-BP. In adjusted analyses, the mean differences in test scores were −1.59 (95% CI −2.48 to −0.71, p < 0.001) between O-mT1D and O-BP and −0.78 (95% CI −1.48 to −0.08, p = 0.03) between O-fT1D and O-BP. No significant difference in the adjusted mean test scores was found between O-mT1D and O-fT1D (p = 0.16). The study’s limitation was no access to measures of glycemic control during pregnancy.ConclusionsO-mT1D achieved lower test scores than O-BP but similar test scores compared with O-fT1D. Glycemic control during pregnancy is essential to prevent various adverse pregnancy outcomes in women with type 1 diabetes. However, the present study reduces previous concerns regarding adverse effects of in utero hyperglycemia on offspring cognitive function.

Anne Lærke Spangmose and colleagues examine the association between school performance and exposure to maternal or paternal type 1 diabetes in utero in Denmark.     

Changes in the associations of race and rurality with SARS-CoV-2 infection,mortality, and case fatality in the United States from February 2020 to March 2021: A population-based cohort study

BackgroundWe examined whether key sociodemographic and clinical risk factors for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and mortality changed over time in a population-based cohort study.Methods and findingsIn a cohort of 9,127,673 persons enrolled in the United States Veterans Affairs (VA) healthcare system, we evaluated the independent associations of sociodemographic and clinical characteristics with SARS-CoV-2 infection (n = 216,046), SARS-CoV-2–related mortality (n = 10,230), and case fatality at monthly intervals between February 1, 2020 and March 31, 2021. VA enrollees had a mean age of 61 years (SD 17.7) and were predominantly male (90.9%) and White (64.5%), with 14.6% of Black race and 6.3% of Hispanic ethnicity. Black (versus White) race was strongly associated with SARS-CoV-2 infection (adjusted odds ratio [AOR] 5.10, [95% CI 4.65 to 5.59], p-value <0.001), mortality (AOR 3.85 [95% CI 3.30 to 4.50], p-value < 0.001), and case fatality (AOR 2.56, 95% CI 2.23 to 2.93, p-value < 0.001) in February to March 2020, but these associations were attenuated and not statistically significant by November 2020 for infection (AOR 1.03 [95% CI 1.00 to 1.07] p-value = 0.05) and mortality (AOR 1.08 [95% CI 0.96 to 1.20], p-value = 0.21) and were reversed for case fatality (AOR 0.86, 95% CI 0.78 to 0.95, p-value = 0.005). American Indian/Alaska Native (AI/AN versus White) race was associated with higher risk of SARS-CoV-2 infection in April and May 2020; this association declined over time and reversed by March 2021 (AOR 0.66 [95% CI 0.51 to 0.85] p-value = 0.004). Hispanic (versus non-Hispanic) ethnicity was associated with higher risk of SARS-CoV-2 infection and mortality during almost every time period, with no evidence of attenuation over time. Urban (versus rural) residence was associated with higher risk of infection (AOR 2.02, [95% CI 1.83 to 2.22], p-value < 0.001), mortality (AOR 2.48 [95% CI 2.08 to 2.96], p-value < 0.001), and case fatality (AOR 2.24, 95% CI 1.93 to 2.60, p-value < 0.001) in February to April 2020, but these associations attenuated over time and reversed by September 2020 (AOR 0.85, 95% CI 0.81 to 0.89, p-value < 0.001 for infection, AOR 0.72, 95% CI 0.62 to 0.83, p-value < 0.001 for mortality and AOR 0.81, 95% CI 0.71 to 0.93, p-value = 0.006 for case fatality). Throughout the observation period, high comorbidity burden, younger age, and obesity were consistently associated with infection, while high comorbidity burden, older age, and male sex were consistently associated with mortality. Limitations of the study include that changes over time in the associations of some risk factors may be affected by changes in the likelihood of testing for SARS-CoV-2 according to those risk factors; also, study results apply directly to VA enrollees who are predominantly male and have comprehensive healthcare and need to be confirmed in other populations.ConclusionsIn this study, we found that strongly positive associations of Black and AI/AN (versus White) race and urban (versus rural) residence with SARS-CoV-2 infection, mortality, and case fatality observed early in the pandemic were ameliorated or reversed by March 2021.

George Ioannou and co-workers study the distribution of SARS-CoV-2 infections and outcomes among the United States population.