Risk of self-harm in patients with eating disorders: English population-based national record-linkage study, 1999-2021.

OBJECTIVE: Anorexia nervosa (AN) and bulimia nervosa (BN) are eating disorders associated with high rates of self-harm (SH). This is the first national study in England to quantify this association in a hospital population. METHOD: A retrospective cohort study using a linked national dataset of Hospital Episode Statistics for 1999-2021. The exposure cohort included individuals aged <35 years admitted to hospital with a diagnosis of AN or BN. The reference cohort included hospital controls. We calculated the rate ratio (RR) of SH in each cohort. The individuals in the two cohorts were matched on multiple socio-demographic indicators. The main outcome was a subsequent hospitalization or death record with an SH diagnosis. RESULTS: We identified 15,004 females and 1411 males with AN, and 6055 females and 741 males with BN. The RR with 95% confidence intervals (95%CI) for a subsequent admission with intentional self-harm after admission with AN was 4.9 (95%CI 4.7-5.1) in females and 4.8 (95%CI 3.9-5.8) in males. For BN it was 9.0 (95%CI 8.4-9.6) in females and 9.8 (95%CI 7.7-12.2) in males. There were strong associations between AN and BN and other SH. DISCUSSION: Women and men admitted to English hospitals with AN or BN have a very high risk of a subsequent admission with SH. For some SH behaviors, such as alcohol intoxication, the RR was >10-fold elevated. The magnitude of risk was higher for BN than for AN. Clinicians should be aware of the scale of risk increase. Providing those at risk with appropriate support is required. PUBLIC SIGNIFICANCE: This study is the first national study in an English hospital population that confirms and quantifies the association between eating disorders and self-harm. We have found that both women and men admitted to hospital with anorexia nervosa or bulimia nervosa are at an increased risk of subsequent admission with self-harm. It is important that clinicians are aware of this increased risk to support those at highest risk of self-harm.

Patterns of unhealthy behaviours during adolescence and subsequent anxiety and depression in adulthood: a prospective register linkage study of the HUNT survey and health registries.

BACKGROUND: There is increasing need for prospective investigations in the preventing role of health-related behaviours on mental health problems. The aim of this study is to identify patterns of health-related behaviours in adolescence, and the association between the behavioural patterns and the subsequent diagnoses and/or drug treatment for anxiety and/or depression in adulthood. METHODS: This prospective study consisted of 13-19-year-old participants in the Trøndelag Health Study (Young-HUNT3) in 2006-2008 (n = 2061, 1205 females and 856 males) in Norway, who also participated in HUNT4 (2017-2019). Survey data on health-related behaviours in adolescence, including low level of physical activity, low consumption of wholegrain bread, fish, fruit, vegetables and high consumption of sugar-sweetened beverages and insomnia were linked on an individual level to prospective information on drug use and diagnosis in national health registries. The different patterns of health-related behaviours were identified through latent class analysis. Subsequent anxiety or depression was defined as at least one recording in either of three registries covering recorded diagnosis in primary and specialist healthcare, or dispensed prescription drugs during 2008-2019. Additionally, self-reported psychological distress measured in young adulthood was applied as a supplemental outcome measure. RESULTS: Four patterns of health-related behaviours were identified: high risk behaviours (class 1), moderate to high risk behaviours (class 2), low to moderate risk behaviours (class 3) and low risk behaviours (class 4). Adolescents in class 3 showed higher odds of subsequent diagnoses for anxiety and/or depression in primary and specialist healthcare compared to class 4 participants. In addition, both class 1 and class 4 participants had higher odds for self-reported psychological distress than those class 4 (OR = 1.56 and OR = 1.86, respectively). CONCLUSIONS: Our findings suggest that health-related behaviours are clustered among Norwegian adolescents. The patterns of unhealthy behaviours during adolescence only partly increased the risk of anxiety and depression in adulthood. Promoting healthy behaviours during adolescence may potentially reduce the burden of mental illness in adulthood, but further research is needed to clarify the nature of the relationships.

Analysis of the risk of complications during pregnancy in pregnant women with assisted reproductive technology: a retrospective study using registry linkage from 2013 to 2018 in Shanghai, China.

BACKGROUND: To evaluate the differences in pregnancy outcomes between assisted reproductive technology (ART) patients and natural pregnant women in Shanghai, China in the past 6 years objectively. And to assess the feasibility of the research method of registry-database linkage in mainland China. METHODS: This retrospective study was conducted using registry-database linkage. A total of 8102 pregnancies with ART and 8096 parturients with spontaneous conception (SC) from 10 reproductive centers and 111 hospitals composed our retrospective study. The primary outcomes were the rates of obstetric complications (pregnancy-induced hypertention [PIH], gestational diabetes mellitus [GDM], placenta previa, mode of delivery, preterm birth [PTB], low birth weight [LBW], and macrosomia). The prenatal outcomes were compared between ART and SC parturients, frozen-thawed embryo transfer (FET) and fresh embryo transfer, and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). We calculated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The final matching rate of the target population was 92% by using registry linkage. ART resulted in a higher rate of multiple birth, PTB, LBW, cesarean section, placenta previa and GDM compared with SC in the singleton cohort. In ART patients, pregnant women with FET had a significantly higher risk of PIH than those with fresh embryo transfer (14.1% Vs 9.3%, AOR1.528, 95% CI 1.303-1.793), but there was no difference between IVF and ICSI. FET is also related to the severity of PIH. CONCLUSIONS: ART increased the rate of complications during pregnancy, the risk and severity of PIH in patients with FET was higher than that in patients with fresh embryo transfer. The registry-database linkage study is an objective and feasible research method in mainland China.

Daytime contacts and general practitioner consultations, and pain as a reason for encounter in children with cerebral palsy; a Norwegian national registry linkage study.

AIM: The aim of this study was to compare the prevalence of daytime contacts and consultations, and pain as a reason for encounter (RFE) with a general practitioner (GP), in children with cerebral palsy (CP) (cases) to that of the general paediatric population (controls). METHODS: The study linked the Norwegian Directorate of Health's database for the control and reimbursement of health expenses, and the Norwegian Quality and Surveillance Registry for Cerebral Palsy, including children born from 1996 to 2012 in the period 2006 to 2018. All daytime contacts were included. International Classification for Primary Care was applied for RFE. RESULTS: Cases accounted for 0.46% of all daytime contacts and 0.27% of all daytime consultations, the latter corresponding with the estimated national prevalence of CP. GPs registered more administrative contact and coded pain as an RFE less frequently in consultations with cases (6%) than with controls (12%). INTERPRETATION: Children with CP did not consult GPs more than the general paediatric population did. In consultations, GPs should ask for pain even if the child with CP or parent does not address pain. The local multidisciplinary team should encourage the family to consider consulting a GP if the child is in pain.KEY MESSAGESPrevalence of GP consultations in children with CP is similar to that of children in the general population.GPs perform more administrative work for children with CP than for their other paediatric patients.GPs code pain as an RFE less frequently in consultations with children with CP than in consultations with children in the general population.

Male factor infertility and risk of death: a nationwide record-linkage study.

STUDY QUESTION: What is the risk of death among men with oligospermia, unspecified male factor and azoospermia in the years following fertility treatment? SUMMARY ANSWER: No significantly elevated risk was observed among men with oligospermia and unspecified male factor, while an increased risk was found among men with azoospermia. WHAT IS KNOWN ALREADY: Previous studies have shown associations between male factor infertility and risk of death, but these studies have relied on internal reference groups and the risk of death according to type of male infertility is not well characterized. STUDY DESIGN, SIZE, DURATION: In this prospective record-linkage cohort study, we identified men who had undergone medically assisted reproduction (MAR) between 1994 and 2015. Data was linked to the Danish causes of death register and sociodemographic registers through personal identification numbers assigned to all Danish citizens at birth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Men that had undergone MAR in Denmark (MAR Cohort; n = 64 563) were identified from the Danish IVF register, which includes data on whether infertility was due to male factor. For each man in the MAR cohort, five age-matched men who became fathers without fertility treatment were selected from the general population (non-MAR fathers; n = 322 108). Men that could not adequately be tracked in the Danish CPR register (n = 1259) and those that were censored prior to study entry (n = 993) were excluded, leaving a final population of 384 419 men. Risk of death was calculated by Cox regression analysis with age as an underlying timeline and adjustments for educational attainment, civil status and year of study entry. The risk of death was compared among men with and without male factor infertility identified from the IVF register (internal comparisons) as well as to the non-MAR fathers (external comparison). MAIN RESULTS AND THE ROLE OF CHANCE: The risk of death between the MAR cohort (all men, regardless of infertility) and the non-MAR fathers was comparable [hazard ratio (HR), 1.07; 95% CI, 0.98-1.15]. When the MAR cohort was limited to infertile men, these men were at increased risk of death [HR, 1.27; 95% CI, 1.12-1.44]. However, when stratified by type of male factor infertility, men with azoospermia had the highest risk of death, which persisted when in both the internal [HR, 2.30; 95% CI, 1.54-3.41] and external comparison [HR, 3.32; 95% CI, 2.02-5.40]. No significantly elevated risk of death was observed among men with oligospermia [HR, 1.14; 95% CI, 0.87-1.50] and unspecified male factor [HR, 1.10; 95% CI, 0.75-1.61] compared with the non-MAR fathers. The same trends were observed for the internal comparison. LIMITATIONS, REASONS FOR CAUTION: Duration of the follow-up was limited and there is limited generalizability to infertile men who do not seek fertility treatment. WIDER IMPLICATIONS OF THE FINDINGS: Using national health registers, we found an increased risk of death among azoospermic men while no increased risk was found among men with other types of infertility. For the azoospermic men, further insight into causal pathways is needed to identify options for monitoring and prevention. STUDY FUNDING/COMPETING INTEREST(S): This study is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS. C.G.'s research stay at Stanford was funded by grants from the University of Copenhagen, Kong Christian den Tiendes Fond, Torben og Alice Frimodt Fond and Julie Von Müllen Fond. M.E. is an advisor for Sandstone and Dadi. All other authors declare no conflict of interests. TRIAL REGISTRATION NUMBER: Not relevant.

Associations between untreated depression and secondary health care utilization in patients with hypertension and/or diabetes.

PURPOSE: We determined the prevalence of untreated depression in patients with hypertension (HT) and/or diabetes (DM) and estimated the extra health care use and expenditures associated with this comorbidity in a rural Hungarian adult population. We also assessed the potential workload of systematic screening for depression in this patient group. METHODS: General health check database from a primary care programme containing survey data of 2027 patients with HT and/or DM was linked to the outpatient secondary care use database of National Institute of Health Insurance Fund Management. Depression was ascertained by Beck Depression Inventory score and antidepressant drug use. The association between untreated depression and secondary healthcare utilization indicated by number of visits and expenses was evaluated by multiple logistic regression analysis controlled for socioeconomic/lifestyle factors and comorbidity. The age-, sex- and education-specific observations were used to estimate the screening workload for an average general medical practice. RESULTS: The frequency of untreated depression was 27.08%. The untreated severe depression (7.45%) was associated with increased number of visits (OR 1.60, 95% CI 1.11-2.31) and related expenses (OR 2.20, 95% CI 1.50-3.22) in a socioeconomic status-independent manner. To identify untreated depression cases among patients with HT and/or DM, an average GP has to screen 42 subjects a month. CONCLUSION: It seems to be reasonable and feasible to screen for depression in patients with HT and/or DM in the primary care, in order to detect cases without treatment (which may be associated with increase of secondary care visits and expenditures) and to initiate the adequate treatment of them.

Novel caries loci in children and adults implicated by genome-wide analysis of families.

BACKGROUND: Dental caries is a common chronic disease among children and adults alike, posing a substantial health burden. Caries is affected by multiple genetic and environmental factors, and prior studies have found that a substantial proportion of caries susceptibility is genetically inherited. METHODS: To identify such genetic factors, we conducted a genome-wide linkage scan in 464 extended families with 2616 individuals from Iowa, Pennsylvania and West Virginia for three dental caries phenotypes: (1) PRIM: dichotomized as zero versus one or more affected primary teeth, (2) QTOT1: age-adjusted quantitative caries measure for both primary and permanent dentitions including pre-cavitated lesions, and (3) QTOT2: age-adjusted quantitative caries excluding pre-cavitated lesions. Genotyping was conducted for approximately 600,000 SNPs on an Illumina platform, pruned to 127,511 uncorrelated SNPs for the analyses reported here. RESULTS: Multipoint non-parametric linkage analyses generated peak LOD scores exceeding 2.0 for eight genomic regions, but no LOD scores above 3.0 were observed. The maximum LOD score for each of the three traits was 2.90 at 1q25.3 for PRIM, 2.38 at 6q25.3 for QTOT1, and 2.76 at 5q23.3 for QTOT2. Some overlap in linkage regions was observed among the phenotypes. Genes with a potential role in dental caries in the eight chromosomal regions include CACNA1E, LAMC2, ALMS1, STAMBP, GXYLT2, SLC12A2, MEGF10, TMEM181, ARID1B, and, as well as genes in several immune gene families. Our results are also concordant with previous findings from association analyses on chromosomes 11 and 19. CONCLUSIONS: These multipoint linkage results provide evidence in favor of novel chromosomal regions, while also supporting earlier association findings for these data. Understanding the genetic etiology of dental caries will allow designing personalized treatment plans based on an individual's genetic risk of disease.

Cardiovascular medication after cancer at a young age in Finland: A nationwide registry linkage study.

Despite improved survival rates, childhood and young adult (YA) cancer survivors face elevated risks for life-threatening morbidities, especially cardiovascular complications. Our nationwide Finnish registry study investigated the purchases of cardiovascular medication from 1993 to 2011 in patients diagnosed with cancer aged below 35 years (N = 8,197) between 1993 and 2004 compared to siblings (N = 29,974) via linkage to the drug purchase registry. The cumulative incidence for purchasing cardiovascular medications was higher in childhood and YA cancer patients compared to siblings with a rising trend over time. After childhood cancer, the highest hazard ratio (HR) was found for purchasing anticoagulants (HR 19.8, 95% CI 8.5-45.9). The HRs for any cardiovascular medication (HR 7.2, 95% CI 5.1-10.1) and cardiac medication (HR 4.8, 95% CI 3.3-6.9) were markedly elevated after childhood cancer as well. Regarding YA cancer patients, the respective HRs were 2.5 (95% CI 2.0-3.2) for anticoagulants, HR 1.7 (95% CI 1.5-1.9) for any cardiovascular medication and HR 1.5 (95% CI 1.3-1.7) for cardiac medication. Among cancer patients, highest HRs for cardiovascular medication were observed after childhood acute lymphoblastic leukemia (ALL) and bone tumors (HR 10.2, 95% CI 6.8-15.5 and HR 7.4, 95% CI 4.0-13.7) and YA ALL and acute myeloid leukemia (HR 5.1, 95% CI 3.5-7.1 and HR 2.8, 95% CI 1.8-4.0). Our study demonstrated increased HRs for purchasing cardiovascular medication after early-onset cancer compared to siblings reflecting elevated cardiovascular morbidity. Thus, the implementation of long-term cardiovascular disease screening is imperative to prevent, detect and adequately treat cardiovascular late effects after cancer at a young age.

Evidence for genetic regulation of the human parieto-occipital 10-Hz rhythmic activity.

Several functional and morphological brain measures are partly under genetic control. The identification of direct links between neuroimaging signals and corresponding genetic factors can reveal cellular-level mechanisms behind the measured macroscopic signals and contribute to the use of imaging signals as probes of genetic function. To uncover possible genetic determinants of the most prominent brain signal oscillation, the parieto-occipital 10-Hz alpha rhythm, we measured spontaneous brain activity with magnetoencephalography in 210 healthy siblings while the subjects were resting, with eyes closed and open. The reactivity of the alpha rhythm was quantified from the difference spectra between the two conditions. We focused on three measures: peak frequency, peak amplitude and the width of the main spectral peak. In accordance with earlier electroencephalography studies, spectral peak amplitude was highly heritable (h(2)  > 0.75). Variance component-based analysis of 28 000 single-nucleotide polymorphism markers revealed linkage for both the width and the amplitude of the spectral peak. The strongest linkage was detected for the width of the spectral peak over the left parieto-occipital cortex on chromosome 10 (LOD = 2.814, nominal P < 0.03). This genomic region contains several functionally plausible genes, including GRID1 and ATAD1 that regulate glutamate receptor channels mediating synaptic transmission, NRG3 with functions in brain development and HRT7 involved in the serotonergic system and circadian rhythm. Our data suggest that the alpha oscillation is in part genetically regulated, and that it may be possible to identify its regulators by genetic analyses on a realistically modest number of samples.

Antibiotic exposure in the first year of life and later treated asthma, a population based birth cohort study of 143,000 children.

Several epidemiological studies reported an association between antibiotic consumption in the first year of life and later asthma, but results are conflicting and affected by potential biases. We examined this controversial issue in a population-based birth cohort. Using administrative data, we identified 143,163 children born in 1995-2011 in Friuli-Venezia Giulia (Italy) (median follow-up 5.25 years, 927,350 person-years). Antibiotic prescriptions in the first year of life and subsequent treated asthma (defined as ≥2 anti-asthmatic drug prescriptions within a 12-month period) were retrieved from drug prescription records. We estimated incidence rate ratios (IRR) using Poisson regression models, adjusted for perinatal variables and for hospitalizations for infections in the first year of life. We identified 34,957 new-onset asthma cases. Antibiotic consumption in the first year of life increased the risk of new-onset asthma [IRR 1.51, 95% confidence interval (CI) 1.48-1.54] with a dose-response relationship (p-trend <0.001). The risk was highest for asthma identified at 13-35 months of life (IRR 2.07, 95% CI 2.00-2.14), but remained statistically significant for asthma identified at 36-71 months (IRR 1.17, 95% CI 1.14-1.21) and at ≥72 months (IRR 1.15, 95% CI 1.08-1.22). Antibiotics increased the risk of current asthma at ≥6 years (IRR 1.35, 95% CI 1.30-1.41) and at ≥13 years of age (IRR 1.19, 95% CI 1.08-1.33). Antibiotic exposure in infancy is associated with an increased risk of asthma up to adolescence. The association detected at older ages is not explained by reverse causation; however, confounding by respiratory infections not leading to hospital admission cannot be excluded.

The economic impact of mental healthcare consumption before and after stroke in a cohort of stroke patients in the Netherlands: a record linkage study.

BACKGROUND: Post-stroke healthcare consumption is strongly associated with a mental health diagnosis. This study aimed to identify stroke patients who utilised mental healthcare facilities, explored their mental healthcare consumption pre-stroke and post-stroke, and examined possible predictors of costs incurred by mental healthcare consumption post-stroke. METHODS: Three databases were integrated, namely the Maastricht University Medical Centre (MUMC) Medical Administration, the Stroke Registry from the Department of Neurology at MUMC, and the Psychiatric Case Registry South-Limburg. Patients from the MUMC who suffered their first-ever stroke between January 1 2000 and December 31 2004 were included and their records were analysed for mental healthcare consumption from 5 years preceding to 5 years following their stroke (1995-2009). Regression analysis was conducted to identify possible predictors of mental healthcare consumption costs. RESULTS: A total of 1385 patients were included and 357 (25.8%) received services from a mental healthcare facility during the 10-year reference period around their stroke. The costs of mental healthcare usage increased over time and peaked 1 year post-stroke (€7057; 22% of total mental healthcare costs). The number of hospitalisation days and mental healthcare consumption pre-stroke were significant predictors of mental healthcare costs. Explained variances of these models (costs during the 5 years post-stroke: R 2 = 15.5%, costs across a 10 year reference period: R 2 = 4.6%,) were low. CONCLUSION: Stroke patients have a significant level of mental healthcare comorbidity leading to relatively high mental healthcare costs. There is a relationship between stroke and mental healthcare consumption costs, but results concerning the underlying factors responsible for these costs are inconclusive.

A Unique Opportunity to Study Short and Long Term Consequences in Children Prenatally Exposed to Illicit Drugs and Opioid Maintenance Treatment Using Czech and Scandinavian Registers.

Licit and illicit drug use in pregnant women constitutes a long lasting and serious problem worldwide. Information on long-term effects of maternal drug use on the child is limited. Nationwide registers provide a great potential to study short and long-term consequences for children exposed to licit and illicit drugs during pregnancy. We discuss this potential, with a special emphasis on exposure to methamphetamine, heroin and prescription drugs used for opioid maintenance treatment (OMT). We also discuss the advantages of register data and of merging such data from different regions. The Czech and Scandinavian registers are largely comparable and provide great opportunities to conduct innovative research. For instance, using Czech and Scandinavian cohorts we can compare groups with similar characteristics, such as mothers in OMT and mothers addicted to other drugs while also controlling for important confounding factors such as health and socio-economic status.

Effects of Food Depictions in Entertainment Media on Children's Unhealthy Food Preferences: Content Analysis Linked With Panel Data.

Background: Entertainment media content is often mentioned as one of the roots of children's unhealthy food consumption. This might be due to the high quantity of unhealthy foods presented in children's media environments. However, less is known about the role of the centrality of food placement, that is, whether foods are interacted with, consumed, verbally mentioned, or appear unobtrusively. We also lack longitudinal research measuring both children's unhealthy and healthy food consumption behaviors as outcomes. Objective: The aim is to connect content analytical data based on children's actual media diet with panel data in order to explain children's food preferences. Moreover, this study not only focuses on the amount of healthy and unhealthy foods children are exposed to, but also on how these foods are presented (ie, centrally or not). Furthermore, we looked at the question of how parental coviewing can diminish (or enhance) the effects of unhealthy (or healthy) food depictions, and we measured healthy and unhealthy consumption as dependent variables. Methods: We conducted a 2-wave panel study with children and one of their parents (of 2250 parents contacted, 829 responded, for a response rate of 36.84%; 648 valid cases, ie, parent-child pairs, were used for analysis), with 6 months between the 2 panel waves. We linked the 2-wave panel data for the children and their parents to content analytical data for movies (n=113) and TV series (n=134; 3 randomly chosen episodes per TV series were used) that children were exposed to over the course of 6 months. Results: There was no significant relationship between exposure to unhealthy food presentation and unhealthy (b=0.008; P=.07) or healthy (b=-0.003; P=.57) food consumption over time. Also, healthy food presentation was unrelated to unhealthy (b=0.009; P=.18) or healthy (b=0.000; P=.99) food consumption over time. However, there was a significant, positive interaction between unhealthy food presentation and presentation centrality on unhealthy food consumption (b=0.000; P=.03), suggesting that the effects of unhealthy food presentation rise with increasing levels of centrality. There was no interaction between unhealthy food presentation and presentation centrality on the consumption of healthy foods (b=0.000; P=.10). Also, exposure to healthy food presentation interacted with centrality (b=-0.001; P=.003). That is, when a healthy product was presented at maximum centrality, it led to less unhealthy food consumption in children. Coviewing did not interact with exposure to unhealthy foods when explaining unhealthy (b=0.003; P=.08) or healthy (b=-0.001; P=.70) food consumption. Conclusions: We conclude that simply presenting more healthy foods is not sufficient to combat children's unhealthy food preferences. Further regulations may be necessary with respect to representations of unhealthy foods in children's media.

Evaluation of the incidence and risk of hypoglycemic coma associated with selection of basal insulin in the treatment of diabetes: a Finnish register linkage study.

OBJECTIVE: Long-acting basal insulin analogs have demonstrated positive effects on the balance between effective glycemic control and risk of hypoglycemia versus neutral protamine Hagedorn (NPH) insulin in randomized controlled trials. Evidence of severe hypoglycemic risk with insulin detemir, insulin glargine, or NPH insulin is presented from a nationwide retrospective database study. RESEARCH DESIGN AND METHODS: Data from hospital and secondary healthcare visits due to hypoglycemic coma from 75 682 insulin-naïve type 1 or 2 diabetes patients initiating therapy with NPH insulin, insulin glargine, or insulin detemir in Finland between 2000 and 2009 were analyzed. Incidence rates with 95% confidence intervals (CIs) were calculated using Poisson regression. Hazard ratios were estimated using Cox's regression with adjustments for relevant background variables. RESULTS: The adjusted risk of hospital/secondary healthcare visits due to the first severe hypoglycemic event was 21.7% (95% CI 9.6-32.1%, p < 0.001) lower for insulin detemir and 9.9% (95% CI 1.5-17.6%, p = 0.022) lower for insulin glargine versus NPH insulin. Risk of hypoglycemic coma recurrence was 36.3% (95% CI 8.9-55.5%, p = 0.014) lower for detemir and 9.5% but not significantly (95% CI -10.2 to 25.7%, p = 0.318) lower for glargine versus NPH insulin. Risk of all hypoglycemic coma events was 30.8% (95% CI 16.2-42.8%, p-value <0.001) lower for detemir and 15.6% (95% CI 5.1-25.0%, p-value 0.005) lower for glargine versus NPH. Insulin detemir had a significantly lower risk for first (13.1% lower [p = 0.034]), recurrent (29.6% lower [p = 0.021]), and all (17.9% lower [p = 0.016]) severe hypoglycemic events than insulin glargine. CONCLUSIONS: There were considerable differences in risk of hospitalization or secondary healthcare visits due to hypoglycemic coma between basal insulin treatments in real-life clinical practice.

Gender differences in physical morbidity in opioid agonist treatment patients: population-based cohort studies from the Czech Republic and Norway.

BACKGROUND: Physical diseases represent a significant burden for opioid agonist treatment (OAT) patients. This study described physical morbidity in two national cohorts of OAT patients focusing on gender differences. METHODS: This population-based cohort study linking multiple health registers investigated physical diseases (ICD-10) in patients receiving OAT in the Czech Republic (N = 4,280) and Norway (N = 11,389) during 2010-2019. Gender-stratified analysis was performed. RESULTS: Overall, we found a large burden of physical morbidity across gender groups in OAT patients. In the Czech Republic and Norway, women in OAT had a significantly higher prevalence of physical diseases across most diagnostic chapters, notably genitourinary diseases and neoplasms. Injuries/external causes and infectious/parasitic diseases were among the most common diseases in both women and men. Viral hepatitis accounted for over half of infectious morbidity in women and men in both cohorts. CONCLUSIONS: Our findings support the need for early screening, detection, and treatment of diseases and conditions across organ systems and the integration of health promotion activities to reduce physical morbidity in OAT patients. The gender differences underline the need for a tailored approach to address specific medical conditions.

Heritability of nervous system tumors: a sibling-based design.

Background: The contribution of genetic and environmental factors to susceptibility to nervous system tumors remains unclear. We performed a quantitative genetic study using a sibling design to estimate the heritability of nervous system tumors, as well as the proportion of the risk of these tumors, which is attributable to environmental factors. Methods: We conducted a population-based cohort study using Swedish National Register data. All individuals born in Sweden during 1950-2010 with available information on both biological parents were included. A Multi-Generation Register was used to identify family clusters, including both full- and half-siblings. Initially, one index person was randomly selected from each cluster containing only full siblings and one sibling was randomly assigned to this index person. Subsequently, within each of the remaining clusters of full- and half-siblings, an index person was randomly selected, and a half-sibling was randomly assigned to this index person. Among the randomly selected siblings, cases of nervous system tumors were identified using the cancer registry. Quantitative genetic models were used to estimate the proportion of the variance in nervous system tumors attributable to additive genetic factors, shared environment, and individual-specific environment. Results: The heritability of nervous system tumors was estimated to be 29% (95% confidence interval (CI) = 19%-39%), while the contribution of the non-shared environment to the variance of nervous system tumors was estimated to be 71% (95% CI = 61%-81%). The shared environmental parameter was estimated as zero in the full model. Conclusion: The variation in susceptibility to nervous system tumors is predominantly attributable to non-shared environmental factors, followed by genetic factors.

Probing the genomic landscape of human sexuality: a critical systematic review of the literature.

Whether human sexuality is the result of nature or nurture (or their complex interplay) represents a hot, often ideologically driven, and highly polarized debate with political and social ramifications, and with varying, conflicting findings reported in the literature. A number of heritability and behavioral genetics studies, including pedigree-based investigations, have hypothesized inheritance patterns of human sexual behaviors. On the other hand, in most twin, adoption, and nuclear family studies, it was not possible to disentangle between underlying genetic and shared environmental sources. Furthermore, these studies were not able to estimate the precise extent of genetic loading and to shed light both on the number and nature of the putative inherited factors, which remained largely unknown. Molecular genetic studies offer an unprecedented opportunity to overcome these drawbacks, by dissecting the molecular basis of human sexuality and allowing a better understanding of its biological roots if any. However, there exists no systematic review of the molecular genetics of human sexuality. Therefore, we undertook this critical systematic review and appraisal of the literature, with the ambitious aims of filling in these gaps of knowledge, especially from the methodological standpoint, and providing guidance to future studies. Sixteen studies were finally retained and overviewed in the present systematic review study. Seven studies were linkage studies, four studies utilized the candidate gene approach, and five studies were GWAS investigations. Limitations of these studies and implications for further research are discussed.

Parental mental health and risk of poor mental health and death by suicide in offspring: a population-wide data-linkage study.

AIMS: Suicide is a major public health concern. Identifying those most at risk is vital to ensure the implementation of effective interventions. Mental health (MH) is known to have a genetic component and parental MH is associated with offspring MH. However, little is known about the effect of parental psychopathology on offspring suicide risk. The aim of this study is to determine if children living with parents with poor MH are at an increased risk of poor MH, or death by suicide. METHODS: This population-wide cohort study linked data from the 2011 Northern Ireland Census to 6 years' death records (2011-2016). Information on MH status, in addition to other individual and household-level attributes, was derived from the 2011 Census. Logistic regression was utilised to examine the association between parental poor MH and offspring MH and suicide risk, with adjustment for socio-demographic characteristics. RESULTS: Overall, 11.6% of the cohort of 618 970 individuals were residing with parents who reported poor MH; 1.6% reported poor MH themselves, and 0.04% (n = 260) died by suicide. Living with a parent with poor MH increased the odds of offspring poor MH (OR = 2.80, 95% CI 2.59-3.03). After adjustment for age, gender, physical illness, socio-economic status and own MH, children living with 1 parent with poor MH were 76% more likely to die by suicide compared to children of parents who did not report poor MH (OR = 1.76, 95% CI 1.31-2.36). The effect size increased for children living with 2 parents with poor MH, and was higher in children aged under 24 years. CONCLUSIONS: Living with a parent with poor MH is a significant risk factor for offspring poor MH and suicide, even after adjustment for personal MH status. When treating mental ill-health in parents, potential interventions for their children should also be considered.

Suicide mortality among psychiatric patients in Northeast Italy: a 10-year cohort study.

AIMS: The present study investigated the relationship between suicide mortality and contact with a community mental health centre (CMHC) among the adult population in the Veneto Region (northeast Italy, population 4.9 million). Specifically, it estimated the effects of age, gender, time elapsed since the first contact with a CMHC, calendar year of diagnosis and diagnostic category on suicide mortality and modality. METHODS: The regional mortality archive was linked to electronic medical records for all residents aged 18-84 years who had been admitted to a CMHC in the Veneto Region in 2008. In total, 54 350 subjects diagnosed with a mental disorder were included in the cohort and followed up for a period of 10 years, ending in 2018. Years of life lost (YLL) were computed and suicide mortality was estimated as a mortality rate ratio (MRR). RESULTS: During the follow-up period, 4.4% of all registered deaths were from suicide, but, given the premature age of death (mean 52.2 years), suicide death accounted for 8.7% of YLL; this percentage was particularly high among patients with borderline personality disorder (27.2%), substance use disorder (12.1%) and bipolar disorder (11.5%) who also presented the highest suicide mortality rates. Suicide mortality rates were halved in female patients (MRR 0.45; 95% CI 0.37-0.55), highest in patients aged 45-54 years (MRR 1.56; 95% CI 1.09-2.23), and particularly elevated in the 2 months following first contact with CMHCs (MRR 10.4; 95% CI 5.30-20.3). A sensitivity analysis restricted to patients first diagnosed in 2008 confirmed the results. The most common modalities of suicide were hanging (47%), jumping (18%), poisoning (13%) and drowning (10%), whereas suicide from firearm was rare (4%). Gender, age at death and time since first contact with CMHCs influenced suicide modality. CONCLUSIONS: Suicide prevention strategies must be promptly initiated after patients' first contact with CMHCs. Patients diagnosed with borderline personality disorder, substance use disorder and bipolar disorder may be at particularly high risk for suicide.

An Investigation of the Role of Common and Rare Variants in a Large Italian Multiplex Family of Multiple Sclerosis Patients.

Known multiple sclerosis (MS) susceptibility variants can only explain half of the disease's estimated heritability, whereas low-frequency and rare variants may partly account for the missing heritability. Thus, here we sought to determine the occurrence of rare functional variants in a large Italian MS multiplex family with five affected members. For this purpose, we combined linkage analysis and next-generation sequencing (NGS)-based whole exome and whole genome sequencing (WES and WGS, respectively). The genetic burden attributable to known common MS variants was also assessed by weighted genetic risk score (wGRS). We found a significantly higher burden of common variants in the affected family members compared to that observed among sporadic MS patients and healthy controls (HCs). We also identified 34 genes containing at least one low-frequency functional variant shared among all affected family members, showing a significant enrichment in genes involved in specific biological processes-particularly mRNA transport-or neurodegenerative diseases. Altogether, our findings point to a possible pathogenic role of different low-frequency functional MS variants belonging to shared pathways. We propose that these rare variants, together with other known common MS variants, may account for the high number of affected family members within this MS multiplex family.