Diverging trends for onset of acute myocardial infarction, heart failure, stroke and mortality in young males: role of changes in obesity and fitness.

BACKGROUND: As opposed to the decreasing overall rates of coronary heart disease (CHD) incidence and overall cardiovascular disease (CVD) mortality, heart failure (HF) and stroke incidence are increasing in young people, potentially due to rising rates of obesity and reduced cardiorespiratory fitness (CRF). OBJECTIVES: We investigated trends in early major CVD outcomes in a large cohort of young men. METHODS: Successive cohorts of Swedish military conscripts from 1971 to 1995 (N = 1,258,432; mean age, 18.3 years) were followed, using data from the National Inpatient and Cause of Death registries. Cox proportional hazard models were used to analyse changes in 21-year CVD event rates. RESULTS: 21-year CVD and all-cause mortality and incidence of acute myocardial infarction (AMI) decreased progressively. Compared with the cohort conscripted in 1971-1975 (reference), the hazard ratios (HRs) for the last 1991-1995 cohort were 0.50 [95% confidence interval (CI) 0.42-0.59] for CVD mortality; 0.57 (95% CI 0.54-0.60) for all-cause mortality; and 0.63 (95% CI 0.53-0.75) for AMI. In contrast, the incidence of ischaemic stroke, intracerebral haemorrhage and HF increased with HRs of 1.43 (95% CI 1.17-1.75), 1.30 (95% CI 1.01-1.68) and 1.84 (95% CI 1.47-2.30), respectively. During the period, rates of obesity increased from 1.04% to 2.61%, whilst CRF scores decreased slightly. Adjustment for these factors influenced these secular trends only moderately. CONCLUSION: Secular trends of young-onset CVD events demonstrated a marked shift from AMI and CVD mortality to HF and stroke incidence. Trends were significantly, though moderately, influenced by changing baseline BMI and CRF.

Approaches to Promoting Linkage to and Retention in HIV Care in the United States: a Scoping Review.

PURPOSE OF REVIEW: Linkage to and retention in HIV care, as conceptualized in the HIV care continuum, remain critical steps towards achieving and maintaining viral suppression. We evaluated recently published (Jan 2018-Nov 2020) peer-reviewed clinical trials of linkage to and retention in care outcomes in the United States. RECENT FINDINGS: We identified 12 trials evaluating linkage to and retention in care outcomes in the United States. Most trials did not adhere to standardized definitions or metrics for linkage to or retention in HIV care, hindering comparisons between studies. Four interventions indicated improvements on linkage to or retention in HIV care at follow-up, relying on behavioral incentives and/or case management as key intervention strategies. We recommend the adoption standardize metrics across linkage and retention trials, and the future use of implementation science frameworks to identify implementation facilitators and barriers, and evaluate key strategies associated with improvements in linkage to and retention in care.

A Scoping Review of HIV Pre-exposure Prophylaxis Stigma and Implications for Stigma-Reduction Interventions for Men and Transwomen Who Have Sex with Men.

HIV remains a public health concern in the United States. Although pre-exposure prophylaxis (PrEP) can be expected to reduce HIV incidence, its uptake, adherence, and persistence remain limited, particularly among highest priority groups such as men who have sex with men and transwomen (MSMTW). Using a socioecological framework, we conducted a scoping review to examine PrEP-related stigma to inform future research, policy, and programmatic planning. Using the PRISMA extension for scoping reviews, we conducted database searches from August 2018 to April 2020 for articles addressing PrEP stigma. Studies were independently screened and coded by three authors, resulting in thematic categorization of several types of PrEP stigma on four socioecological levels. Of 557 references, a final sample of 23 studies was coded, 61% qualitative, and 87% focusing exclusively on MSMTW. Most instances of PrEP-related stigma occurred on the interpersonal level and included associations of PrEP with risk promotion, HIV-related stigma, and promiscuity. Other frequent themes across socioecological levels included provider distrust and discrimination, government and pharmaceutical industry distrust, internalized homonegativity, PrEP efficacy distrust, and anticipated homonegativity. Notably, PrEP was also framed positively as having physical and psychological benefits, and assuming responsibility for protecting one's community via PrEP awareness-raising. PrEP-related stigma persists, demanding interventions to modify its impact. Leveraging PrEP-positive discourses to challenge PrEP stigma is an emerging avenue, alongside efforts to increase provider willingness to promote PrEP routinely by reducing provider bias, aligning with the national strategy to End the HIV Epidemic.

Obesity in adolescent men increases the risk of venous thromboembolism in adult life.

BACKGROUND: As the population of obese and severely obese young adults grows, it is becoming increasingly important to recognize the long-term risks associated with adolescent obesity. OBJECTIVES: This study aimed to determine the association between body mass index (BMI) in young men at enlistment for military service and later risk of venous thromboembolism (VTE). METHODS: Nationwide register-based prospective cohort study of men enlisting 1969 to 2005, followed through the Swedish National Patient and Cause of Death registries. We identified 1 639 838 men (mean age, 18.3 years) free of prior venous thromboembolism, of whom 29 342 were obese (BMI 30 to <35 kg m-2 ) and 7236 severely obese (BMI ≥ 35 kg m-2 ). The participants were followed until a first registered diagnosis of VTE. RESULTS: During a median follow-up of 28 years (interquartile interval, 20 to 36 years), 11 395 cases of deep vein thrombosis and 7270 cases of pulmonary embolism were recorded. Compared with men with a BMI of 18.5 to <20 kg m-2 , men with higher BMI in young adulthood showed an incrementally increasing risk of VTE that was moderately but significantly increased already at normal BMI levels. Adolescent obese men with a BMI of 30 to 35 kg m-2 had an adjusted hazard ratio of 2.93 (95% confidence interval, 2.65 to 3.24) for VTE. Severely obese men with a BMI of ≥35 kg m-2 had a hazard ratio of 4.95 (95% confidence interval, 4.16 to 5.90). CONCLUSIONS: Men who were obese or severely obese in young adulthood had a marked increase in risk of VTE.

Type 1 diabetes in children born after assisted reproductive technology: a register-based national cohort study.

STUDY QUESTION: Do children born after assisted reproductive technology (ART) have an increased risk of developing type 1 diabetes? SUMMARY ANSWER: Children born after ART were found to have an increased risk of type 1 diabetes in the unadjusted analysis, while after adjustment this association was only significant in children born after frozen embryo transfer. WHAT IS KNOWN ALREADY?: Some studies raise concerns as to whether fertility treatments may influence long-term morbidity in children born after ART. Elevated blood pressure and altered glucose metabolism have been found after ART in a few studies. STUDY DESIGN, SIZE, DURATION: A register-based national cohort study that included all children born in Sweden between 1985 and 2015-in total, 3 138 540 children-was carried out. PARTICIPANTS/MATERIAL, SETTING, METHODS: The study was population-based and all live-born singleton children born after ART (n = 47 938) or spontaneous conception (SC) (n = 3 090 602) were included. The ART cohort comprised 36 727 children born after fresh embryo transfer and 11 211 children born after frozen embryo transfer. Several national registries were used together with data from Statistics Sweden. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 202 children born after ART and 17 916 children born after SC developed type 1 diabetes, corresponding to 43.4 and 35.5 per 100 000 person-years at risk (hazard ratio [HR] 1.23; 95% confidence interval [CI], 1.07 to 1.42). Mean follow-up was 9.7 (SD 6.4) years for ART children and 16.3 (SD 9.2) years for SC children. After adjustment for calendar year of birth, HR for type 1 diabetes was 1.13; 95% CI, 0.98-1.30. After further adjustment for sex, maternal age, country of birth, educational level, smoking and parental diabetes, HR was 1.07; 95% CI, 0.93-1.23. In subgroup analyses, an association was found between frozen embryo transfer and type 1 diabetes (adjusted HR 1.52; 95% CI, 1.08-2.14 and 1.41; 95% CI, 1.05-1.89 for frozen versus fresh and frozen versus SC, respectively). When comparing intracytoplasmic sperm injection to in vitro fertilization, no difference was found (adjusted HR 1.08; 95% CI, 0.77-1.51). LIMITATIONS, REASONS FOR CAUTION: Limitations were the missing data and residual confounding caused by unknown confounders. Furthermore, the control group consisted of all children not conceived by ART and not non-ART children from subfertile mothers. The study was also performed in only singletons and not in the total ART population. WIDER IMPLICATIONS OF THE FINDINGS: Type 1 diabetes is a serious disease, affecting human life in several ways, including risk of serious complications, reduced life span and a life-long treatment. Our results are generally reassuring, showing no increase in diabetes in ART children compared to children born after SC after adjustment for relevant confounders. The observation of an association between children born after frozen embryo transfer and type 1 diabetes, although based on subgroup analyses with a limited number of children and modest in size, is however a reason for concern. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by Nordforsk 71450, the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement 70940, and the Hjalmar Svensson Foundation. The authors have no competing interests. TRIAL REGISTRATION NUMBER: ISRCTN 11780826.

Visit patterns at primary care centres and individual blood pressure level - a cross-sectional study.

OBJECTIVE: Hypertension is a major cause of cardiovascular disease. Nevertheless, blood pressure (BP) is often inadequately treated. We studied visit patterns at primary health care centres (PHCCs) and their relation to individual BP control. DESIGN AND SETTING: Cross-sectional register-based study on all patients with hypertension who visited 188 PHCCs in a Swedish region. PATIENTS: A total of 88,945 patients with uncomplicated hypertension age 40-79. MAIN OUTCOME MEASURES: Odds ratio (OR) for the individual patient to achieve the BP target of ≤140/90 mmHg. RESULTS: Overall, 63% of patients had BP ≤ 140/90 mmHg (48% BP < 140/90). The PHCC that the patient was enrolled at and, as part of that, more nurse visits at PHCC level was associated with BP control, adjusted OR 1,10 (95% CI 1.01 to 1.21). Patients visiting PHCCs with the highest proportion of visits with nurses had an even higher chance of achieving the BP target, OR 1.19 (95% CI 1.07 to 1.32). CONCLUSIONS: In a Swedish population of patients with hypertension, about half do not achieve recommended treatment goals. Organisation of PHCC and team care are known as factors influencing BP control. Our results suggests that a larger focus on PHCC organisation including nurse based care could improve hypertension care.

Cardiovascular disease in diabetes type 2: current concepts.

Type 2 diabetes is a major and accelerating public health challenge. Between 1980 and 2014, a period of just 35 years, the number of adults with diabetes globally is estimated to have increased from 108 to 422 million, due not only to sharply rising obesity rates, but also to increasing population size, longer life expectancy, and rising prevalence of diabetes worldwide. Overall, worldwide age-standardized adult diabetes prevalence doubled from 4.3% to 9.0% in men and from 5.0% to 7.9% in women. The largest increases in diabetes type 2 have been demonstrated in low- and middle-income countries, whilst rises in high-income countries have been less marked, or even flat. Diabetes type 2 rates in low- and middle-income countries now in many instances surpass those in high-income countries, in response to changes in lifestyle. One factor of particular concern are the large relative increases in type 2 diabetes amongst young individuals observed in many countries, their higher overall risk factor burden, long exposure to hyperglycaemia and greater risk of complications over the life course. Type 2 diabetes is increasingly found to be a heterogeneous condition, where risk of cardiovascular disease that traditionally has been estimated at 2-4 times that of the nondiabetic population varies substantially with diabetes phenotype and accordingly diabetes does not confer the same increase in relative or absolute risk in all people. New research shows that excess risk varies substantially with type of outcome, age, glycaemic control, the presence of renal complications and other factors. Heart failure, previously less recognized that other cardiovascular conditions, is increasingly coming into focus, because of strong links with poor glycaemic control and obesity. The knowledge about risk of cardiovascular disease in diabetes is almost entirely derived from high-income countries, whereas there is comparatively very little data from low- and middle income countries, where the majority of persons with type 2 diabetes live, and where management in many cases is far from optimal. The reductions in cardiovascular disease incidence and mortality now observed in high-income countries are encouraging, because this reinforces the fact that improvement is possible and that a near-normal, or even normal life-expectancy can be achieved in subtypes of type 2 diabetes.

BMI change during puberty and the risk of heart failure.

AIM: Hospitalization for heart failure amongst younger men has increased. The reason for this is unknown but it coincides with the obesity epidemic. The aim of this study was to evaluate the association between childhood BMI (Body Mass Index) and BMI change during puberty for risk of adult heart failure in men. METHODS: Using the BMI Epidemiology Study (BEST), a population-based study in Gothenburg, Sweden, we collected information on childhood BMI at age 8 years and BMI change during puberty (BMI at age 20 - BMI at 8) for men born 1945-1961, followed until December 2013 (n = 37 670). BMI was collected from paediatric growth charts and mandatory military conscription tests. Information on heart failure was retrieved from high-quality national registers (342 first hospitalizations for heart failure). RESULTS: BMI change during puberty was independently of childhood BMI associated with risk of heart failure in a nonlinear J-shaped manner. Subjects in the upper quartile of BMI change during puberty (Q4) had more than twofold increased risk of heart failure compared with subjects in Q1 [HR (Hazard Ratio) = 2.29, 95% CI (Confidence Interval) 1.68-3.12]. Childhood BMI was not independently associated with risk of heart failure. Boys developing overweight during puberty (HR 3.14; 95% CI 2.25-4.38) but not boys with childhood overweight that normalized during puberty (HR 1.12, 95% CI 0.63-2.00) had increased risk of heart failure compared with boys without childhood or young adult overweight. CONCLUSION: BMI change during puberty is a novel risk factor for adult heart failure in men.

Cardiovascular fitness in late adolescent males and later risk of serious non-affective mental disorders: a prospective, population-based study.

BACKGROUND: Cardiovascular fitness in late adolescence is associated with future risk of depression. Relationships with other mental disorders need elucidation. This study investigated whether fitness in late adolescence is associated with future risk of serious non-affective mental disorders. Further, we examined how having an affected brother might impact the relationship. METHOD: Prospective, population-based cohort study of 1 109 786 Swedish male conscripts with no history of mental illness, who underwent conscription examinations at age 18 between 1968 and 2005. Cardiovascular fitness was objectively measured at conscription using a bicycle ergometer test. During the follow-up (3-42 years), incident cases of serious non-affective mental disorders (schizophrenia and schizophrenia-like disorders, other psychotic disorders and neurotic, stress-related and somatoform disorders) were identified through the Swedish National Hospital Discharge Register. Cox proportional hazards models were used to assess the influence of cardiovascular fitness at conscription and risk of serious non-affective mental disorders later in life. RESULTS: Low fitness was associated with increased risk for schizophrenia and schizophrenia-like disorders [hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.29-1.61], other psychotic disorders (HR 1.41, 95% CI 1.27-1.56), and neurotic or stress-related and somatoform disorders (HR 1.45, 95% CI 1.37-1.54). Relationships persisted in models that included illness in brothers. CONCLUSIONS: Lower fitness in late adolescent males is associated with increased risk of serious non-affective mental disorders in adulthood.

Glycaemic control and excess risk of ischaemic and haemorrhagic stroke in patients with type 1 diabetes: a cohort study of 33 453 patients.

OBJECTIVE: To estimate the excess risk of stroke in relation to glycaemic control in patients with type 1 diabetes. METHODS: In this prospective, matched cohort study, we identified patients with type 1 diabetes, aged ≥18 years, who were registered in the Swedish National Diabetes Register from 1998-2011 and five control subjects for each case from the general population, matched for age, sex and county of residence. The risks of all strokes, ischaemic stroke and haemorrhagic stroke were estimated using Cox hazard regression. RESULTS: Of 33 453 type 1 diabetes patients [mean age, 35.5 (SD 14.4) years; mean follow-up, 7.9 (SD 4.3) years; and mean diabetes duration, 20.2 years (SD 14.6)], 762 (2.3%) were diagnosed with stroke compared with 1122 (0.7%) of 159 924 control subjects [mean follow-up, 8.2 (SD 4.3) years]. The overall multiple-adjusted hazard ratios (HRs) for type 1 diabetes patients versus control subjects were 3.29 (95% CI: 2.96-3.66) and 2.49 (95% CI: 1.96-3.16) for ischaemic and haemorrhagic stroke, respectively. The risk of ischaemic and haemorrhagic stroke incrementally increased with increasing HbA1c; the risk of ischaemic stroke was significantly increased with HbA1c within target [≤6.9% (≤52 mmol mol-1 )] [multiple-adjusted HR 1.89 (95% CI: 1.44-2.47)]. For HbA1c ≥9.7% (≥83 mmol mol-1 ), there was a markedly increased risk of both ischaemic and haemorrhagic stroke, with multiple-adjusted HRs of 7.94 (95% CI: 6.29-10.03) and 8.17 (95% CI 5.00-13.35), respectively. CONCLUSIONS: Individuals with type 1 diabetes have an increased risk of ischaemic and haemorrhagic stroke, increasing markedly with poor glycaemic control.

Long-term excess risk of stroke in people with Type 2 diabetes in Sweden according to blood pressure level: a population-based case-control study.

AIMS: To estimate the risk of stroke in people with Type 2 diabetes with different blood pressure levels compared with the risk in the general population in Sweden. METHODS: This prospective case-control study included 408 076 people with Type 2 diabetes, aged ≥ 18 years, and free of prior stroke, registered in the Swedish National Diabetes Register 1998-2011. Age- and sex-matched control subjects (n = 1 913 507) without stroke from the general population were included. Stroke diagnoses were retrieved using International Classification of Disease codes from the Swedish patient and death registers. Cox hazard ratios and 95% confidence intervals (CIs) were estimated at six different blood pressure levels. RESULTS: During a median follow-up of 4 years, 19 548 (4.8%) people with Type 2 diabetes and 61 690 (3.2%) without diabetes were diagnosed with stroke, corresponding to an adjusted hazard ratio of 1.43 (95% CI 1.41-1.46) for people with Type 2 diabetes as a group. Compared with people without diabetes, the risk of stroke for people with Type 2 diabetes with different blood pressure levels was significantly higher, starting at blood pressure levels > 130/80 mmHg. Hazard ratios for stroke were 1.20 (95% CI 1.16-1.24), 1.47 (95% CI 1.43-1.50), and 1.97 (95% CI 1.90-2.03) for blood pressure categories of 130-139/80-89 mmHg, 140-159/90-99 mmHg and ≥ 160/≥ 100 mmHg, respectively, after adjustment for age, sex, diabetes duration, being born in Sweden, maximum education level and baseline comorbidities. CONCLUSIONS: People with Type 2 diabetes and blood pressure < 130/80 mmHg had a risk of stroke similar to that of the general population.

The Swedish CArdioPulmonary BioImage Study: objectives and design.

Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.

Psychosocial factors and obesity in 17 high-, middle- and low-income countries: the Prospective Urban Rural Epidemiologic study.

BACKGROUND/OBJECTIVES: Psychosocial stress has been proposed to contribute to obesity, particularly abdominal, or central obesity, through chronic activation of the neuroendocrine systems. However, these putative relationships are complex and dependent on country and cultural context. We investigated the association between psychosocial factors and general and abdominal obesity in the Prospective Urban Rural Epidemiologic study. SUBJECTS/METHODS: This observational, cross-sectional study enrolled 151 966 individuals aged 35-70 years from 628 urban and rural communities in 17 high-, middle- and low-income countries. Data were collected for 125 290 individuals regarding education, anthropometrics, hypertension/diabetes, tobacco/alcohol use, diet and psychosocial factors (self-perceived stress and depression). RESULTS: After standardization for age, sex, country income and urban/rural location, the proportion with obesity (body mass index ≥30 kg m(-)(2)) increased from 15.7% in 40 831 individuals with no stress to 20.5% in 7720 individuals with permanent stress, with corresponding proportions for ethnicity- and sex-specific central obesity of 48.6% and 53.5%, respectively (P<0.0001 for both). Associations between stress and hypertension/diabetes tended to be inverse. Estimating the total effect of permanent stress with age, sex, physical activity, education and region as confounders, no relationship between stress and obesity persisted (adjusted prevalence ratio (PR) for obesity 1.04 (95% confidence interval: 0.99-1.10)). There was no relationship between ethnicity- and sex-specific central obesity (adjusted PR 1.00 (0.97-1.02)). Stratification by region yielded inconsistent associations. Depression was weakly but independently linked to obesity (PR 1.08 (1.04-1.12)), and very marginally to abdominal obesity (PR 1.01 (1.00-1.03)). CONCLUSIONS: Although individuals with permanent stress tended to be slightly more obese, there was no overall independent effect and no evidence that abdominal obesity or its consequences (hypertension, diabetes) increased with higher levels of stress or depression. This study does not support a causal link between psychosocial factors and abdominal obesity.

The association between BMI and hospitalization for heart failure in 83,021 persons with Type 2 diabetes: a population-based study from the Swedish National Diabetes Registry.

AIM'S: The aim was to To study the relationship between BMI and hospitalization for heart failure in people with Type 2 diabetes. METHODS: We identified 83 021 individuals with Type 2 diabetes from the Swedish National Diabetes Registry during 1998-2003, who were followed until hospitalization for heart failure, death or end of follow-up on 31 December 2009. Cox regression analyses were performed, adjusting for age, sex, HbA(1c), blood pressure, diabetes duration, smoking, microalbuminuria, cardiac co-morbidities, glucose-lowering and anti-hypertensive medications. RESULTS: During a median follow-up of 7.2 years, 10 969 patients (13.2%) were hospitalized with heart failure. By categories of BMI, with BMI 20 to < 25 kg/m(2) as the reference, hazard ratios for patients during follow-up were 1.07 (95% CI 0.91-1.26) for a mean BMI of < 20 kg/m(2), 1.04 (95% CI 0.98-1.11) for BMI 25 to < 27.5 kg/m(2), 1.22 (95% CI 1.15-1.30) for BMI 27.5 to < 30 kg/m(2), 1.54 (95% CI 1.45-1.63) for BMI 30 to < 35 kg/m(2), 2.16 (95% CI 2.00-2.33) for BMI 35 to < 40 kg/m(2) and 3.22 (95% CI 2.88-3.60) for BMI 40 kg/m(2) or higher. There was a significant interaction between BMI and sex (P = 0.0006), with numerically higher hazard ratios for hospitalization for heart failure within each BMI category for men than for women. CONCLUSIONS: Obesity is strongly related to hospitalization for heart failure in people with Type 2 diabetes, and the relationship is somewhat stronger for men than for women. Preventing weight gain and promoting weight loss may be crucial in reducing the incidence of future hospitalizations for heart failure in this population.

Incidence of Type 2 diabetes among occupational classes in Sweden: a 35-year follow-up cohort study in middle-aged men.

AIMS: To assess if low occupational class was an independent predictor of Type 2 diabetes in men in Sweden over a 35-year follow-up, after adjustment for both conventional risk factors and psychological stress. METHODS: A random population-based sample of 6874 men aged 47-56 years without a history of diabetes was divided into five occupational classes and the men were followed from 1970 to 2008. Diabetes cases were identified through the Swedish inpatient and death registers. Subdistribution hazard ratios (SHRs) and 95% CIs from competing risk regressions, cumulative incidence and conditional probabilities were calculated, after accounting for the risk of death attributed to other causes. RESULTS: A total of 907 (13%) men with diabetes were identified over 35 years with a median follow-up of 27.9 years. The cumulative incidence of diabetes, when taking into account death as a competing event, was 11% in high officials, 12% in intermediate non-manual employees, 14% in assistant non-manual employees, 14% in skilled workers, and 16% in unskilled and semi-skilled workers. Men with unskilled and semi-skilled manual occupations had a significantly higher risk of diabetes than high officials (reference) after adjustment for age, BMI, hypertension, smoking and physical activity (SHR 1.39, 95% CI 1.08-1.78). Additional adjustment for self-reported psychological stress did not attenuate the results. CONCLUSIONS: A low occupational class suggests a greater risk of Type 2 diabetes, independently of conventional risk factors and psychological stress.

Clinical segmentation in 22q11.2 deletion syndrome: Cognitive impairments and additional genetic load.

The 22q11.2 deletion syndrome (22q11.2DS) is associated with high psychiatric morbidity. However, large phenotypic heterogeneity hampers early detection of 22q11.2DS individuals at highest risk. Here, we investigated whether individuals with 22q11.2DS can be subdivided into clinically relevant subgroups based on their severity of cognitive impairments and whether such subgroups differ in polygenic risk. Using a cross-sectional design, we examined the number of lifetime psychiatric diagnoses and polygenic risk scores for schizophrenia in an unselected nationwide biobank cohort of individuals with 22q11.2DS (n = 183). Approximately 35% of this sample, aged 10-30 years, had a history with one or more psychiatric diagnosis. In a representative nested subgroup of 28 children and youth, we performed additional comprehensive cognitive evaluation and assessed psychiatric symptoms. Unsupervised hierarchical cluster analysis was performed to divide the subgroup of 22q11.2DS individuals, based on their performance on the cognitive testing battery. This produced two groups that did not differ in mean age or gender composition, but were characterized by low cognitive (LF) and high cognitive (HF) functional levels. The LF group, which had significantly lower global cognitive functioning scores, also displayed higher negative symptom scores; whereas, the HF group displayed lower rate of current psychiatric disorders than the LF group and the reminder of the biobank cohort. The polygenic risk score for schizophrenia was insignificantly lower for the low functioning group than for the high functioning group, after adjustment. Cognitive functioning may provide useful information on psychiatric risk.

Internalized HIV stigma and viral suppression: examining the mediating and moderating roles of substance use and social support.

OBJECTIVE: To examine the effects of internalized HIV stigma on viral non-suppression via depressive symptoms, alcohol use, illicit drug use, and medication adherence and investigate whether social support moderates these effects. DESIGN: Longitudinal observational clinical cohort of patients in HIV care in the US.Methods: Data from the CFAR Network for Integrated Clinical Systems (2016-2019) were used to conduct structural equation models (SEM) to test the indirect effects of internalized HIV stigma on viral non-suppression through depressive symptoms, illicit drug use, alcohol use, and medication adherence. Moderated mediation with an interaction between social support and internalized HIV stigma was examined. RESULTS: Among 9,574 individuals included in the study sample, 81.1% were male and 41.4% were Black, non-Hispanic. The model demonstrated good fit (root mean square error of approximation = 0.028; standardized root means square residual = 0.067). The overall indirect effect was significant (b = 0.058; se  = 0.020; ß = 0.048; 95%CI = .019-.098), indicating that internalized HIV stigma's impact on viral non-suppression was mediated by depressive symptoms, illicit drug use, and medication adherence. An interaction was observed between internalized HIV stigma and social support on alcohol use, however, there was no moderated mediation for any of the mediators. CONCLUSIONS: Internalized HIV stigma indirectly impacts viral non-suppression through its effects on depressive symptoms, illicit drug use, and medication adherence. Social support may buffer the impact, but more research is needed. Understanding the pathways through which internalized stigma impacts viral suppression is key to improving health of people with HIV.

Perceived stress and incidence of Type 2 diabetes: a 35-year follow-up study of middle-aged Swedish men.

AIM: To explore incident cases of diagnosed diabetes over 35 years of follow-up in relation to self-perceived stress at baseline. METHODS: This was a population-based random sample of 7251 men derived from the Primary Prevention Trial Study, aged 47-56 years at baseline and without prior history of diabetes, coronary heart disease and stroke. Incident diabetes was identified from hospital discharge and death registries as principal or secondary diagnosis. Cox proportional hazards regression was used to evaluate the potential association between stress and diabetes. RESULTS: During a 35-year follow-up, a total of 899 men were identified with diabetes. The crude incidence was 5.2 per 1000 persons-years. At baseline, 15.5% men reported permanent stress related to conditions at work or home. After adjusting for age and competing risk of death, the estimated 35-year conditional probability of diabetes in men with permanent stress was 42.6%, compared with 31.0% for those with periodic stress and 31.2% with no stress. In age-adjusted Cox regression analysis, men with permanent stress had a higher risk of diabetes [hazard ratio 1.52 (95% CI 1.26-1.82)] compared with men with no (referent) or periodic stress [hazard ratio 1.09 (95% CI 0.94-1.27)]. The association between stress and diabetes was slightly attenuated but remained significant after adjustment for age, socio-economic status, physical inactivity, BMI, systolic blood pressure and use of anti-hypertensive medication [hazard ratio 1.45 (95% CI 1.20-1.75)]. When examining principal diagnosis of diabetes cases separately from secondary diagnoses cases, the excess risk of diabetes associated with permanent stress remained significant both in age (only) and multivariable adjusted models. CONCLUSION: Self-perceived permanent stress is an important long-term predictor of diagnosed diabetes, independently of socio-economic status, BMI and other conventional Type 2 diabetes risk factors.

The relationship between glycaemic control and heart failure in 83,021 patients with type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to examine the relationship between glycaemic control and hospitalisation for heart failure in patients with type 2 diabetes. METHODS: Patients included in the Swedish National Diabetes Register (NDR) during 1998-2003 were followed until hospitalisation for heart failure, death or 31 December 2009. Unadjusted and adjusted incidence rates for heart failure were estimated by Poisson regression and relative risk was estimated by Cox regression. RESULTS: In 83,021 patients with type 2 diabetes, 10,969 (13.2%) were hospitalised with a primary or secondary diagnosis of heart failure during a mean follow-up of 7.2 years. The incidence increased by male sex (p < 0.001), older age (p < 0.001) and longer diabetes duration (p < 0.001). In Cox regression adjusting for risk factors of heart failure the HR per each percentage unit higher HbA(1c) (10 mmol/mol) for heart-failure hospitalisation was 1.12 (95% CI 1.10, 1.14). By category of HbA(1c) the HR for heart failure hospitalisation was: HbA(1c) 6.0 to <7.0% (42 to <53 mmol/mol), 0.91 (95% CI 0.84, 0.98); HbA(1c) 7.0 to <8.0% (53 to <64 mmol/mol), 0.99 (95% CI 0.91, 1.07); HbA(1c) 8.0 to <9.0% (64 to < 75 mmol/mol), 1.10 (95% CI 1.01, 1.20); HbA(1c) 9.0 to <10.0% (75 to <86 mmol/mol), 1.27 (95% CI 1.15, 1.41); HbA(1c) ≥ 10.0 % (≥ 86 mmol/mol), 1.71 (1.51, 1.93) (reference HbA(1c) <6% [42 mmol/mol]). The HR for patients with HbA(1c) 7.0 to <8.0% (53 to < 64 mmol/mol) compared with patients with HbA(1c) 6.0 to <7.0% (42 to <53 mmol/mol) was 1.09 (95% CI 1.03, 1.14). CONCLUSIONS/INTERPRETATION: Poor glycaemic control (HbA(1c) >7% [53 mmol/mol]) is associated with an increased risk of hospitalisation for heart failure in patients with type 2 diabetes.