Potential of a second screening test for alloimmunization in pregnancies of Rhesus-positive women: a Swedish population- based cohort study.

INTRODUCTION: There is lack of consensus regarding whether a second screening in Rhesus-positive pregnant women is worthwhile, with different guidelines, recommendations, and practices. We aimed to estimate the number and timing of missed alloimmunizations in Rhesus-positive pregnancies screened once and weigh the relative burden of additional screening and monitoring versus the estimated reduction in adverse pregnancy outcomes. METHODS: We extracted information on maternal, pregnancy, and screening results for 682,126 pregnancies for 2003-2012 from Swedish national registers. We used data from counties with a routine second screening to develop and validate a logistic model for a positive second test after an earlier negative. We used this model to predict the number of missed alloimmunizations in counties offering only one screening. Interval-censored survival analysis identified an optimal time window for a second test. We compared the burden of additional screening with estimated adverse pregnancy outcomes avoided. RESULTS: The model provided an accurate estimate of positive tests at second screening. For counties with the lowest screening rates, we estimated that a second screening would increase the alloimmunization prevalence by 33% (from 0.19% to 0.25%), detecting the 25% (304/1222) of cases that are currently missed. The suggested timing of a second screen was gestational week 28.For pregnancies currently screened once, the estimated cost of a second test followed by maternal monitoring was approximately 10% the cost incurred by the excess adverse pregnancy outcomes. CONCLUSION: Investment in routine second screening can identify many alloimmunizations that currently go undetected or are detected late, with the potential for cost savings.

Association between childhood trauma and depressive symptoms in adolescents during the post COVID-19 pandemic: the mediating role of social peer rejection.

This study aimed to investigate the associations of childhood trauma and its facets with depressive symptoms in depressed adolescents during the post COVID-19 epidemic, and explore the potential mediating role of social peer rejection in these associations. A total of 413 adolescents with depressive disorders completed the Chinese version of the Child Trauma Questionnaire Short Form, the Social Peer Rejection, and the Children's Depression Inventory. Childhood trauma (ß = 0.42, p < 0.01) and social peer rejection (ß = 0.18, p < 0.01) were positively related to depressive symptoms, after adjustment for demographic factors. Furthermore, social peer rejection partly mediated the relationship between childhood trauma and depressive symptoms, and the mediation effect ratio was 17.0% (p < 0.001). This study found that childhood trauma and social peer rejection are both risk factors for depressive symptoms, and social peer rejection played a mediating role in the relationship between childhood trauma and depressive symptoms.

Effect of Additives on CO2 Adsorption of Polyethylene Polyamine-Loaded MCM-41.

Organic amine-modified mesoporous carriers are considered potential CO2 sorbents, in which the CO2 adsorption performance was limited by the agglomeration and volatility of liquid amines. In this study, four additives of ether compounds were separately coimpregnated with polyethylene polyamine (PEPA) into MCM-41 to prepare the composite chemisorbents for CO2 adsorption. The textural pore properties, surface functional groups and elemental contents of N for MCM-41 before and after functionalization were characterized; the effects of the type and amount of additives, adsorption temperature and influent velocity on CO2 adsorption were investigated; the amine efficiency was calculated; and the adsorption kinetics and regeneration for the optimized sorbent were studied. For 40 wt.% PEPA-loaded MCM-41, the CO2 adsorption capacity and amine efficiency at 60 °C were 1.34 mmol/g and 0.18 mol CO2/mol N, when the influent velocity of the simulated flue gas was 30 mL/min, which reached 1.81 mmol/g and 0.23 mol CO2/mol N after coimpregnating 10 wt.% of 2-propoxyethanol (1E). The maximum adsorption capacity of 2.16 mmol/g appeared when the influent velocity of the simulated flue gas was 20 mL/min. In addition, the additive of 1E improved the regeneration and kinetics of PEPA-loaded MCM-41, and the CO2 adsorption process showed multiple adsorption routes.

Borderline personality disorder: associations with psychiatric disorders, somatic illnesses, trauma, and adverse behaviors.

In one of the largest, most comprehensive studies on borderline personality disorder (BPD) to date, this article places into context associations between this diagnosis and (1) 16 different psychiatric disorders, (2) eight somatic illnesses, and (3) six trauma and adverse behaviors, e.g., violent crime victimization and self-harm. Second, it examines the sex differences in individuals with BPD and their siblings. A total of 1,969,839 Swedish individuals were identified from national registers. Cumulative incidence with 95% confidence intervals (CI) was evaluated after 5 years of follow-up from BPD diagnosis and compared with a matched cohort. Associations were estimated as hazard ratios (HR) with 95% CIs from Cox regression. 12,175 individuals were diagnosed with BPD (85.3% female). Individuals diagnosed with BPD had higher cumulative incidences and HRs for nearly all analyzed indicators, especially psychiatric disorders. Anxiety disorders were most common (cumulative incidence 95% CI 33.13% [31.48-34.73]). Other notable findings from Cox regressions include psychotic disorders (HR 95% CI 24.48 [23.14-25.90]), epilepsy (3.38 [3.08-3.70]), violent crime victimization (7.65 [7.25-8.06]), and self-harm (17.72 [17.27-18.19]). HRs in males and females with BPD had overlapping CIs for nearly all indicators. This indicates that a BPD diagnosis is a marker of vulnerability for negative events and poor physical and mental health similarly for both males and females. Having a sibling with BPD was associated with an increased risk for psychiatric disorders, trauma, and adverse behaviors but not somatic disorders. Clinical implications include the need for increased support for patients with BPD navigating the health care system.

Use of benzodiazepine and Z-drugs and mortality in older adults after myocardial infarction.

BACKGROUND: The adverse cardiovascular effects of benzodiazepines and Z-drugs (jointly referred as BZDRs) have been of concern. Yet, little is known about the use of BZDRs in relation to mortality risk among older adults with myocardial infarction history (post-MI). METHODS: This study is a secondary analysis of the Alpha Omega Cohort study, comprising post-MI patients aged 40-60 years. Self-reported information on the use of BZDRs, including types and dose, was collected at baseline. Four categories of mortality were examined, namely all-cause mortality, cardiovascular (CVD) mortality, cancer mortality, and non-CVD/non-cancer mortality. Associations between BZDRs use, by types and doses, and mortality were estimated with Cox regression models, adjusted for demographic and classic cardiovascular risk factors. RESULTS: A total of 433 (8.9%) out of 4837 (21.8% females) patients reported BZDRs use at baseline. During a median follow-up of 12.4 years, 2287 deaths were documented, of which 825 (36.1%) were due to CVD. BZDRs use was related to a statistically significantly higher risk of all-cause and CVD mortality; adjusted hazard ratios [95% CI] were (1.31 [1.41, 1.52]) and (1.43 [1.14, 1.81]), respectively. These relationships were dose-dependent-patients using BZDRs on an as-needed basis had similar risks compared to the non-uses, whereas patients with a daily use schedule and increasing doses had higher risks (p-value for trend: <0.001). CONCLUSION: BZDRs use was independently associated with a higher risk of all-cause and cardiovascular mortality in older post-MI patients, and there was evidence for a dose-dependent relationship. CLINICAL TRIAL REGISTRATION: NCT00127452 (www. CLINICALTRIALS: gov).

Childhood-onset type 1 diabetes and attention-deficit/hyperactivity disorder with educational attainment: A population-based sibling-comparison study.

AIM: To examine the association of childhood-onset type 1 diabetes (T1D) and attention-deficit/hyperactivity disorder (ADHD) with educational outcomes from compulsory school to university. METHODS: Using multiple Swedish nationwide registers, we followed up on 1,474,941 individuals born in Sweden from 1981-1995 to December 31, 2013. Associations of T1D and ADHD with achieving educational milestones (from compulsory school to university) and school performances were estimated using logistic and linear regression models and sibling comparison models. RESULTS: Compared to their peers, children with both T1D and ADHD were less likely to achieve any of the educational attainments, including completing compulsory school (adjusted OR [aOR] [95% CI]: 0.43 [0.26, 0.72]), be eligible to and finishing upper secondary school (0.26 [0.19, 0.36], 0.24 [0.17, 0.35], respectively), and starting university (0.38 [0.17, 0.90]). The odds of achieving these educational milestones were substantially lower in children with ADHD alone (aORs: 0.14-0.44), but were slightly worse or no differences in children with T1D alone (aORs: 0.86-1.08). All associations above remained similar in the sibling comparison models. CONCLUSION: Children and adolescents with both T1D and ADHD had long-term educational underachievement, with ADHD being the major contributor. Our findings suggest the importance of assessing ADHD in children with T1D and targeted support for minimising the education gap between the affected children and their peers.

Poor glycaemic control is associated with increased risk of neurodevelopmental disorders in childhood-onset type 1 diabetes: a population-based cohort study.

AIMS/HYPOTHESIS: The aim of this study was to investigate the effect of childhood-onset type 1 diabetes on the risk of subsequent neurodevelopmental disorders, and the role of glycaemic control in this association. We hypothesised that individuals with poor glycaemic control may be at a higher risk of neurodevelopmental disorders compared with the general population, as well as compared with individuals with type 1 diabetes with adequate glycaemic control. METHODS: This Swedish population-based cohort study was conducted using data from health registers from 1973 to 2013. We identified 8430 patients with childhood-onset type 1 diabetes (diagnosed before age 18 years) with a median age of diabetes onset of 9.6 (IQR 5.9-12.9) and 84,300 reference individuals from the general population, matched for sex, birth year and birth county. Cox models were used to estimate the effect of HbA1c on the risk of subsequent neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD) and intellectual disability. RESULTS: During a median follow-up period of 5.6 years, 398 (4.7%) individuals with type 1 diabetes received a diagnosis of any neurodevelopmental disorder compared with 3066 (3.6%) in the general population, corresponding to an adjusted HR (HRadjusted) of 1.31 (95% CI 1.18, 1.46) after additionally adjusting for other psychiatric morbidity prior to inclusion, parental psychiatric morbidity and parental highest education level. The risk of any neurodevelopmental disorder increased with HbA1c levels and the highest risk was observed in patients with mean HbA1c >8.6% (>70 mmol/mol) (HRadjusted 1.90 [95% CI 1.51, 2.37]) compared with reference individuals without type 1 diabetes. In addition, when compared with patients with diabetes with HbA1c <7.5% (<58 mmol/mol), patients with HbA1c >8.6% (>70 mmol/mol) had the highest risk of any neurodevelopmental disorder (HRadjusted 3.71 [95% CI 2.75, 5.02]) and of specific neurodevelopmental disorders including ADHD (HRadjusted 4.16 [95% CI 2.92, 5.94]), ASD (HRadjusted 2.84 [95% CI 1.52, 5.28]) and intellectual disability (HRadjusted 3.93 [95% CI 1.38, 11.22]). CONCLUSIONS/INTERPRETATION: Childhood-onset type 1 diabetes is associated with an increased risk of neurodevelopmental disorders, with the highest risk seen in individuals with poor glycaemic control. Routine neurodevelopmental follow-up visits should be considered in type 1 diabetes, especially in patients with poor glycaemic control.

Inhibition of miR-1224 suppresses hypoxia/reoxygenation-induced oxidative stress and apoptosis in cardiomyocytes through targeting GPX4.

We have focused on the underlying role of miR-1224 in cardiomyocyte injury stimulated by hypoxia/reoxygenation (H/R). In the current study, the rat cardiomyocyte cell line H9C2 was used to construct a H/R cell model to validate the cardioprotective effects of miR-1224. Data from the dual-luciferase assay revealed that the glutathione peroxidase 4 (GPX4) was a direct target of miR-1224. Expression of miR-1224, determined using qRT-PCR, was remarkably increased while that of GPX4 protein, evaluated via western blotting, was significantly decreased in cardiomyocytes in response to H/R exposure. ROS generation, superoxide dismutase (SOD) activity, concentrations of malondialdehyde (MDA) and 4-hydroxy aldehydes (4-HNE), and H9C2 cell apoptosis were further evaluated following overexpression of miR-1224 or silencing of GPX4 in H9C2 cells. H9C2 cells under H/R conditions displayed increased synthesis of ROS, along with overexpression of miR-1224 and downregulation of GPX4. SOD activity was significantly decreased while concentrations of MDA and 4-HNE were markedly increased under H/R injury conditions. In addition, miR-1224 mimic or GPX4 siRNA plasmids dramatically enhanced H/R-mediated apoptosis, Bax expression and caspase-3 activity, with a concomitant reduction in Bcl-2 expression. Conversely, inhibition of miR-1224 exerted suppressive effects on oxidative stress and apoptosis in H9C2 cells under H/R conditions. Interestingly, silencing of GPX4 attenuated the negative effects of miR-1224 inhibition. Our results suggested that inhibition of miR-1224 caused resistance to H/R and diminished oxidative stress in vitro through targeting of GPX4.

Management and clinical consequences of red blood cell antibodies in pregnancy: A population-based cohort study.

INTRODUCTION: Anti-D alloimmunization is the most common cause of severe hemolytic disease of the fetus and newborn (HDFN). The management of pregnancies affected by less frequent red blood cell (RBC) antibodies poses a challenge to clinicians, and perinatal outcomes are less well described. This study aimed to describe the frequency of clinically significant RBC antibodies in our pregnant population and analyze the risk of prenatal and postnatal treatment for HDFN in relation to our national risk classification system and management guidelines. MATERIAL AND METHODS: A retrospective cohort study in the population of all alloimmunized singleton pregnancies in the Stockholm region 1990-2016. Descriptive summaries of different RBC antibodies and pregnancy outcomes were presented, the risks of intrauterine blood transfusion (IUT) and neonatal treatment for HDFN were estimated by type of antibodies. RESULTS: Of the 1724 alloimmunized pregnancies, 1079 (63%) were at risk of HDFN and constituted our study cohort. Anti-D was detected in 492 (46%) pregnancies, followed by anti-E in 161 (15%), and anti-c in 128 (12%). Eighty-seven (8%) pregnancies had IUT, with the highest risk in pregnancies affected by anti-D combined with other antibodies. The maximum titer recorded before IUT was 64 or above, except for two pregnancies affected by anti-c, for which the maximum titers were 8 and 16. For the 942 (95%) live-born neonates from 992 alloimmunized pregnancies without IUT, the median gestational age at birth was 38+5  weeks compared with 35+5  weeks for those who had IUT. Neonatal treatment was most common in the anti-D alone and anti-D combined groups, with 136 (57%) and 21 (44%), respectively, treated with phototherapy and 35 (15%) and 9 (20%) receiving exchange transfusions, respectively. For pregnancies complicated by moderate- and low-risk antibodies, phototherapy was less frequent (32 [36%] and 21 [19%]) and exchange transfusion was rare (5 [6%] and 3 [3%]). CONCLUSIONS: Anti-D, especially in combination with other antibodies, presents the highest risk of severe HDFN. The classification of less frequent and less well-known RBC antibodies into risk groups can help clinicians in assessing the risk of HDFN and counseling alloimmunized pregnant women regarding the risk of prenatal and postnatal treatments.

Effect of B vitamins supplementation on cardio-metabolic factors in patients with stable coronary artery disease: A randomized double-blind trial.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate whether B vitamins supplementation would improve dyslipidemia, alleviate inflammatory state of patients with stable coronary artery disease (SCAD). METHODS AND STUDY DESIGN: We conducted a randomized, double-blind, 12-week, placebo-controlled trial involving adults with SCAD, and who were randomly divided into B vitamins group (folic acid and VB-6) and control group (placebo tablet). Blood tests had also been performed at baseline and endpoint. RESULTS: After 12 weeks of intervention, B vitamins supplementation significantly improved the concentration of serum TG, TC and HDL-C (p<0.05). Changes of serum homocysteine in B vitamins treatment were significantly different compared to placebo by the multivariate-adjusted analysis (3.02±2.35 vs 1.55±1.58 p<0.001). Meanwhile, the levels of IL-1ß and IL-10, significant difference were observed between two groups after adjustment for confounding factors. CONCLUSIONS: Supplementation with B vitamins significantly improves lipid metabolism, alleviate inflammation and serum homocysteine concentration in patients with SCAD.

Intake of dietary saturated fatty acids and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort: associations by types, sources of fatty acids and substitution by macronutrients.

PURPOSE: The association between dietary saturated fatty acids (SFA) intake and type 2 diabetes (T2D) remains unclear. This study aimed at investigating the association between SFA intake and T2D risk based on (1) individual SFA (differing in carbon chain length), (2) food sources of SFA and (3) the substituting macronutrients. METHODS: 37,421 participants from the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort were included in this study. Baseline dietary intake was assessed by a validated food frequency questionnaire. T2D risks were estimated by Cox regression models adjusted for non-dietary and dietary covariates. RESULTS: 893 incident T2D cases were documented during 10.1-year follow-up. We observed no association between total SFA and T2D risk. Marginally inverse associations were found for lauric acid (HR per 1 SD of energy%, 95% CI 0.92, 0.85-0.99), myristic acid (0.89, 0.79-0.99), margaric acid (0.84, 0.73-0.97), odd-chain SFA (pentadecylic plus margaric acids; 0.88, 0.79-0.99), and cheese derived SFA (0.90, 0.83-0.98). Soft and liquid fats derived SFA was found related to higher T2D risk (1.08, 1.01-1.17). When substituting SFA by proteins, carbohydrates and polyunsaturated fatty acids, significantly higher risks of T2D were observed (HRs per 1 energy% ranging from 1.05 to 1.15). CONCLUSION: In this Dutch population, total SFA does not relate to T2D risk. Rather, the association may depend on the types and food sources of SFA. Cheese-derived SFA and individual SFA that are commonly found in cheese, were significantly related to lower T2D risks. We cannot exclude the higher T2D risks found for soft and liquid fats derived SFA and for substituting SFA with other macronutrients are influenced by residual confounding by trans fatty acids or limited intake variation in polyunsaturated fatty acids and vegetable protein.

Electronic devices and myopic refraction among children aged 6-14 years in urban areas of Tianjin, China.

PURPOSE: To assess associations between different types of electronic devices, myopic refraction and ocular biometric parameters in children aged 6-14 years in urban areas of Tianjin, China. METHODS: A school-based, cross-sectional study was performed on 566 children (302 boys and 264 girls). The children underwent a comprehensive eye examination, including cycloplegic autorefraction and ocular biometry. The children's parents completed a detailed questionnaire that included each child's demographics, the use of electronic devices and other related risk factors. RESULTS: Myopia was not associated with time spent using various electronic devices. However, the mean spherical equivalent refraction (SER) decreased by 0.28 D (p = 0.042) and 0.33 D (p = 0.018) for each 1-h increase in the time spent using smart phones and computers, respectively. In the multiple linear regression analyses of factors associated with the SER, the standardised coefficient B for time spent reading and writing was approximately four to five times larger than the standardised coefficient for time spent using smart phones or computers. Time spent using tablets and watching television was not significantly associated with the SER. A longer axial length (AL) was associated with more time spent using smart phones (B = 0.23, p = 0.006) and computers (B = 0.26, p = 0.002) but not using tablets (p = 0.45) and watching television (p = 0.45). No significant association was found between other ocular biometric parameters and time spent using various electronic devices. CONCLUSIONS: On average, a more myopic SER and longer AL were both associated with more time spent using smart phones and computers, but not with time spent using tablets and watching television. The magnitude of the association between SER and time spent reading and writing was a substantially larger than that for smart phone or computer use. Different types of electronic devices had differing levels of association with myopic refraction.

The impact of dementia caregiving on self-care management of caregivers and facilitators: a qualitative study.

BACKGROUND: Caregivers of patients with dementia or Alzheimer's disease (AD) face special health challenges due to the progressive nature of the disease. Self-care has crucial importance on individuals' management of life, health, and well-being. However, limited evidence is available on self-care management of dementia and AD caregivers. This study aimed to investigate the influence of caregiving on the self-care management of dementia and AD caregivers based on the caregivers' experience. In addition, the facilitators of caregivers' self-care management were assessed. METHODS: A sample of 45 caregivers of patients with dementia or AD was recruited from a local community in the south-eastern USA. Semi-structured interviews were conducted. Data were transcribed verbatim and analyzed by the method of cross-case thematic analysis of qualitative data. RESULTS: As reported by the caregivers, caregiving negatively influenced their self-care management, including physical self-care and mental and social self-care. Both internal and external facilitators were found that can assist caregivers' self-care. Caregivers differ considerably in their demographic characteristics, caregiving tasks, and self needs. CONCLUSION: Self-care management of dementia and AD caregivers can be largely affected by caregiving. Awareness, motivation, and knowledge of self-care, as well as knowledge of health-care resources, are important prerequisites for caregivers to achieve self-care management. Given the massive differences in caregiving situations, future intervention studies based on the specific needs of individual caregivers are warranted.

P300 amplitude and latency in autism spectrum disorder: a meta-analysis.

Autism spectrum disorder (ASD) is an early onset neurodevelopmental disorder. Evidence suggests that ASD patients have abnormalities in information processing. Event-related potential (ERP) technique can directly record brain neural activity in real time. P300 is a positive ERP component which can measure the neuroelectrophysiological characteristics of human beings and has the potential to discover the pathological mechanism of ASD. However, P300 studies on ASD patients are incongruent and the disparities may be caused by several factors. By searching PubMed, Embase and Cochrane Library databases, a meta-analysis of P300 component difference between ASD group and typically developed (TD) control group was conducted. Results of amplitude and latency of P3b and P3a from included studies were synthesized. Random effect model was chosen and standardized mean difference (SMD) was calculated. Subgroup analysis was used to identify the source of heterogeneity and to test the effect of different experiment factors. A total of 407 ASD patients and 457 TD controls from 32 studies were included in this analysis. Reduced amplitude of P3b was found in ASD group (SMD = -0.505, 95 % CI -0.873, -0.138) compared with TD group, but no difference of P3b latency, P3a amplitude, or P3a latency was found between groups. Subgroup analysis showed that oddball paradigm elicited attenuated P3b amplitude in Pz electrode among ASD subjects. This meta-analysis suggests ASD patients have abnormalities in P300 component, which may represent for deficits in cognition, attention orientation and working memory processing, particularly in the decision-making processing condition.

Serum Helicobacter pylori CagA antibody may not be used as a tumor marker for diagnosing gastric cancer in east Asian countries.

Gastric cancer (GC) is a highly malignant cancer with increasing incidence and mortality worldwide. Serum Helicobacter pylori CagA antibody has been widely reported to play an important role in diagnosing GC. However, published data on this subject are inconclusive. Therefore, we performed a meta-analysis to evaluate the sensitivity and specificity of serum H. pylori CagA antibody in the diagnosis of GC. We conducted a comprehensive search to identify eligible related studies, in which the pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves could be determined. A total of 12 studies including 1,524 cases and 3,324 controls who fulfilled all of the inclusion criteria were included for analysis. The summary estimates for serum H. pylori CagA antibody in the diagnosis of GC in these studies were pooled sensitivity 0.71 (95 % CI 0.69-0.73), specificity 0.40 (95 % CI 0.39-0.42), DOR 2.11 (95 % CI 1.55-2.8), and the area under the curve was 0.636. Our meta-analysis showed that serum H. pylori CagA antibody should not be used for detecting GC.

Familial aggregation and heritability of childhood-onset and adult-onset type 1 diabetes: a Swedish register-based cohort study.

BACKGROUND: Type 1 diabetes in children is known to be highly heritable, but much less is known about the heritability of adult-onset type 1 diabetes. Thus, our objective was to compare the familial aggregation and heritability of type 1 diabetes in adults and children. METHODS: This Swedish nationwide register-based cohort study included individuals born from Jan 1, 1982, to Dec 31, 2010, identified through the Medical Birth Register who were linked to their parents, full siblings, half siblings, and cousins through the Multi-Generation Register (MGR). We excluded multiple births, deaths within the first month of life, individuals who could not be linked to MGR, or individuals with contradictory information on sex. Information on diagnoses of type 1 diabetes was retrieved by linkages to the National Diabetes Register and National Patient Register (1982-2020). Individuals with inconsistent records of diabetes type were excluded. We estimated the cumulative incidence and hazard ratios (HRs) of type 1 diabetes in adults (aged 19-30 years) and children (aged 0-18 years) by family history of type 1 diabetes and the heritability of adult-onset and childhood-onset type 1 diabetes based on tetrachoric correlations, using sibling pairs. FINDINGS: 2 943 832 individuals were born in Sweden during the study period, 2 832 755 individuals were included in the analysis of childhood-onset type 1 diabetes and 1 805 826 individuals were included in the analysis of adult-onset type 1 diabetes. 3240 cases of adult-onset type 1 diabetes (median onset age 23·4 years [IQR 21·1-26·2]; 1936 [59·7%] male and 1304 [40·2%] female) and 17 914 cases of childhood-onset type 1 diabetes (median onset age 9·8 years [6·2-13·3]; 9819 [54·8%] male and 8095 [45·2%] female) developed during follow-up. Having a first-degree relative with type 1 diabetes conferred an HR of 7·21 (95% CI 6·28-8·28) for adult-onset type 1 diabetes and 9·92 (9·38-10·50) for childhood-onset type 1 diabetes. The HR of developing type 1 diabetes before the age 30 years was smaller if a first-degree relative developed type 1 diabetes during adulthood (6·68 [6·04-7·39]) rather than during childhood (10·54 [9·92-11·19]). Similar findings were observed for type 1 diabetes in other relatives. Heritability was lower for adult-onset type 1 diabetes (0·56 [0·45-0·66]) than childhood-onset type 1 diabetes (0·81 [0·77-0·85]). INTERPRETATION: Adult-onset type 1 diabetes seems to have weaker familial aggregation and lower heritability than childhood-onset type 1 diabetes. This finding suggests a larger contribution of environmental factors to the development of type 1 diabetes in adults than in children and highlights the need to identify and intervene on such factors. FUNDING: Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, Swedish Diabetes Foundation, and the China Scholarship Council.

Substance use-related problems in mild intellectual disability: A Swedish nationwide population-based cohort study with sibling comparison.

Background: Evidence for substance use-related problems in individuals with mild intellectual disability is sparse and mainly limited to selected psychiatric populations. We evaluated the risk of substance use-related problems in individuals with mild intellectual disability compared to the general population. Additionally, we have performed secondary sibling comparison analyses to account for familial confounding. Methods: We conducted a population-based cohort study of individuals born in Sweden between 1973 and 2003. A total of 18,307 individuals with mild intellectual disability were compared to 915,350 reference individuals from the general population and 18,996 full siblings of individuals with mild intellectual disability. Information on mild intellectual disability and substance use-related problems was obtained from several Swedish national and regional school and healthcare registers. Substance use-related problems were measured via corresponding diagnostic and legal codes and included alcohol use disorder, drug use disorder, alcohol-related somatic disease, conviction for a substance-related crime, and substance-related death. Results: Individuals with mild intellectual disability had a higher risk of any substance use-related problem compared to the general population (HR, 1.81; 95% CI, 1.72-1.91), both in males (HR, 1.76; 95% CI, 1.65-1.89) and females (HR, 1.89; 95% CI, 1.74-2.05). The risks of substance use-related problems were particularly elevated among individuals with mild intellectual disability and psychiatric comorbidities (HR, 2.21-8.24). The associations were attenuated in the sibling comparison models. Conclusions: Individuals with mild intellectual disability, especially those with psychiatric comorbidity, are at an elevated risk of substance use-related problems. Familial factors shared by full siblings contribute considerably to the association between mild intellectual disability and substance use-related problems.

Cumulative ADHD medication use and risk of type 2 diabetes in adults: a Swedish Register study.

BACKGROUND: Little is known about the impact of cumulative attention-deficit/hyperactivity disorder (ADHD) medication use on the risk of type 2 diabetes (T2D). OBJECTIVE: The objective is to examine the association between cumulative use of ADHD medication and risk of incident T2D. METHODS: A nested case-control study was conducted in a national cohort of individuals aged 18-70 years with incident ADHD (n=138 778) between 2007 and 2020 through Swedish registers. Individuals with incident T2D after ADHD were selected as cases (n=2355) and matched with up to five controls (n=11 681) on age at baseline, sex and birth year. Conditional logistic regression models examined the association between cumulative duration of ADHD medication use and T2D. FINDINGS: Compared with no use, a decreased risk of T2D was observed for those on cumulative use of ADHD medications up to 3 years (ORs: 03 years, 0.97 (95% CI, 0.84 to 1.12)). When investigating medication types separately, methylphenidate showed results similar to main analyses, lisdexamfetamine showed no association with T2D, whereas long-term (>3 years) use of atomoxetine was associated with an increased risk of T2D (OR: 1.44 (95% CI, 1.01 to 2.04)). CONCLUSION: Cumulative use of ADHD medication does not increase the risk for T2D, with the exception of long-term use of atomoxetine. CLINICAL IMPLICATIONS: Findings suggest that clinicians should be aware of the potential risk of T2D associated with the cumulative use of atomoxetine among patients with ADHD; however, further replication is strongly needed.

Bringing an end to diabetes stigma and discrimination: an international consensus statement on evidence and recommendations.

People with diabetes often encounter stigma (ie, negative social judgments, stereotypes, prejudice), which can adversely affect emotional, mental, and physical health; self-care, access to optimal health care; and social and professional opportunities. To accelerate an end to diabetes stigma and discrimination, an international multidisciplinary expert panel (n=51 members, from 18 countries) conducted rapid reviews and participated in a three-round Delphi survey process. We achieved consensus on 25 statements of evidence and 24 statements of recommendations. The consensus is that diabetes stigma is driven primarily by blame, perceptions of burden or sickness, invisibility, and fear or disgust. On average, four in five adults with diabetes experience diabetes stigma and one in five experience discrimination (ie, unfair and prejudicial treatment) due to diabetes, such as in health care, education, and employment. Diabetes stigma and discrimination are harmful, unacceptable, unethical, and counterproductive. Collective leadership is needed to proactively challenge, and bring an end to, diabetes stigma and discrimination. Consequently, we achieved unanimous consensus on a pledge to end diabetes stigma and discrimination.

Impact of Chronic Kidney Disease on Outcomes of Percutaneous Coronary Intervention in Patients With Diabetes Mellitus: A Systematic Review and Meta-Analysis.

BACKGROUND: The impact of chronic kidney disease (CKD) on adverse cardiovascular outcomes after percutaneous coronary intervention in patients with diabetes mellitus (DM) is still unclear. This study aimed to systematically assess evidence on this topic. METHODS: The PubMed, Embase, and CENTRAL databases were searched for studies comparing mortality, myocardial infarction (MI), or revascularization outcomes between patients with DM with and without CKD. RESULTS: In 11 studies, the presence of CKD was associated with significantly increased risk of early all-cause mortality (risk ratio [RR], 3.45; 95% CI, 3.07-3.87; I2 = 0%; P < .001), late all-cause mortality (RR, 2.78; 95% CI, 1.92-4.02; I2 = 83%; P < .001), cardiac mortality (RR, 2.90; 95% CI, 1.99-4.22; I2 = 29%; P < .001), and MI (RR, 1.40; 95% CI, 1.06-1.85; I2 = 13%; P = .02) compared with no CKD. There was no difference in the risk of any revascularization between those with and without CKD. Analysis of adjusted hazard ratios (HRs) indicated significantly increased risk of mortality (HR, 2.64; 95% CI, 1.91-3.64; I2 = 0%; P < .001) in the CKD group but only a nonsignificant tendency of increased MI (HR, 1.59; 95% CI, 0.99-2.54; I2 = 0%; P = .05) and revascularization (HR, 1.24; 95% CI, 0.94-1.63; I2 = 2%; P = .12) in the CKD group. CONCLUSION: The presence of CKD in patients with DM significantly increases the risk of mortality and MI. However, CKD had no impact on revascularization rates.