Incidence, prevalence and risk factors for hepatitis C in Danish prisons

Hepatitis C virus (HCV) infection is prevalent among people in prison and prisons could therefore represent a unique opportunity to test risk groups for HCV. The aim of this sero-epidemiological study was to determine the incidence and prevalence of HCV infection and the corresponding risk factors in Danish prisons. Participants, recruited from eight Danish prisons, were tested for HCV using dried blood spots and filled out a questionaire with demographic data and risk factors for HCV infection. In total, 76.9% (801/1041) of all eligible prisoners consented to participate. The prevalence of HCV RNA positive prisoners was 4.2% (34/801) and the in-prison incidence rate was 0.7-1.0 per 100PY overall and 18-24/100PY among PWIDs. Infected prisoners were older than the overall population with a mean age of 42 years and only 17.6% (6/34) were younger than 35 years. The prevalence of PWID was 8.5% (68/801) and only 3% (2/68) of PWID were younger than 25 years. Among the PWID, 85.3% (58/68) had ever received opioid substitution therapy (OST) and 47.1% (32/68) were currently receiving OST. Risk factors associated with HCV infection were intravenous drug use, age ≥ 40 years, and being incarcerated ≥ 10 years. In conclusion, the prevalence of PWID in Danish prisons is low, possibly reflecting a decrease in injecting among the younger generation. This together with OST coverage could explain the low prevalence of HCV infection. However among PWIDs in prison the incidence remains high, suggesting a need for improved HCV prevention in prison

Hepatitis C prevalence in Denmark in 2016-An updated estimate using multiple national registers

Background: Chronic hepatitis C (CHC) can be eliminated as a public health threat by meeting the WHO targets: 90% of patients diagnosed and 80% treated by 2030. To achieve and monitor progress towards elimination, an updated estimate of the size of the CHC population is needed, but Denmark has no complete national CHC register. By combining existing registers in 2007, we estimated the population living with CHC to be 16,888 (0.38% of the adult population). Aim: To estimate the population living with diagnosed and undiagnosed CHC in Denmark on 31 December 2016. Among additional aims were to estimate the proportion of patients attending specialised clinical care. Methods: People with diagnosed CHC were identified from four national registers. The total diagnosed population was estimated by capture-recapture analysis. The undiagnosed population was estimated by comparing the register data with data from two cross-sectional surveys. Results: The population living with diagnosed CHC in Denmark was 7,581 persons (95%CI: 7,416-12,661) of which 6,116 (81%) were identified in the four registers. The estimated undiagnosed fraction was 24%, so the total CHC infected population was 9,975 corresponding to 0.21% of the adult population (95%CI: 9,758-16,659; 0.21%-0.36%). Only 48% of diagnosed patients had received specialised clinical care. Conclusion: CHC prevalence in Denmark is declining and 76% of patients have been diagnosed. Linking diagnosed patients to care and increasing efforts to test people with former or current drug use will be necessary to achieve CHC elimination

Low incidence of HCC in chronic hepatitis C patients with pretreatment liver stiffness measurements below 17.5 kilopascal who achieve SVR following DAAs

Background and aimsTo evaluate the ability of pretreatment liver stiffness measurements (pLSM) to predict hepatocellular carcinoma (HCC), incident decompensation and all-cause mortality in chronic hepatitis C (CHC) patients who achieved sustained virological response (SVR) after treatment with direct-acting antivirals (DAAs).Methods773 CHC patients with SVR after DAA treatment and no prior liver complications were identified retrospectively. Optimized cut-off of 17.5 kPa for incident HCC was selected by maximum Youden's index. Patients were grouped by pLSM: ResultsMedian follow-up was 36 months and 43.5% (336) had cirrhosis (LSM>12.5 kPa). The median pLSM was 11.6 kPa (IQR 6.7-17.8, range 2.5-75) and pLSM of ConclusionPretreatment LSM predicts risk of HCC, decompensation and all-cause mortality in patients with SVR after DAA treatment. Patients with a pLSM <17.5 kPa and no other risk factors for chronic liver disease appear not to benefit from HCC surveillance for the first 3 years after treatment. Longer follow-up is needed to clarify if they can be safely excluded from post treatment HCC screening hereafter

Return to Work After Refractory Out-of-Hospital Cardiac Arrest in Patients Managed With or Without Extracorporeal Cardiopulmonary Resuscitation: A Nationwide Register-Based Study

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used for refractory out-of-hospital cardiac arrest (OHCA). However, survivors managed with ECPR are at risk of poor functional status. The purpose of this study was to investigate return to work (RTW) after refractory OHCA.METHODS AND RESULTS: Of 44 360 patients with OHCA in the period of 2011 to 2020, this nationwide registry-based study included 805 patients with refractory OHCA in the working age (18-65 years) who were employed before OHCA (2% of the total OHCA cohort). Demographics, prehospital characteristics, status at hospital arrival, employment status, and survival were retrieved through the Danish national registries. Sustainable RTW was defined as RTW for ≥6 months without any long sick leave relapses. Median follow-up time was 4.1 years. ECPR and standard advanced cardiovascular life support were applied in 136 and 669 patients, respectively. RTW 1 year after OHCA was similar (39% versus 54%; P=0.2) and sustainable RTW was high in both survivors managed with ECPR and survivors managed with standard advanced cardiovascular life support (83% versus 85%; P&gt;0.9). Younger age and shorter length of hospitalization were associated with RTW in multivariable Cox analysis, whereas ECPR was not.CONCLUSIONS: In refractory OHCA-patients employed prior to OHCA, approximately 1 out of 2 patients were employed after 1 year with no difference between patients treated with ECPR or standard advanced cardiovascular life support. Younger age and shorter length of hospitalization were associated with RTW while ECPR was not.</p

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Genetic Overlap Between Alzheimer’s Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes

Background: Alzheimer's disease (AD) and bipolar disorder (BIP) are complex traits influenced by numerous common genetic variants, most of which remain to be detected. Clinical and epidemiological evidence suggest that AD and BIP are related. However, it is not established if this relation is of genetic origin. Here, we applied statistical methods based on the conditional false discovery rate (FDR) framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits. Methods: We obtained genome wide association studies data from the International Genomics of Alzheimer's Project part 1 (17,008 AD cases and 37,154 controls) and the Psychiatric Genetic Consortium Bipolar Disorder Working Group (20,352 BIP cases and 31,358 controls). We used conditional QQ-plots to assess overlap in common genetic variants between AD and BIP. We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework. Results: Conditional QQ-plots demonstrated a polygenic overlap between AD and BIP. Using conditional FDR, we identified one novel genomic locus associated with AD, and nine novel loci associated with BIP. Further, we identified two novel loci jointly associated with AD and BIP implicating the MARK2 gene (lead SNP rs10792421, conjunctional FDR=0.030, same direction of effect) and the VAC14 gene (lead SNP rs11649476, conjunctional FDR=0.022, opposite direction of effect). Conclusions: We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci. Further studies should examine if the shared loci implicating the MARK2 and VAC14 genes could explain parts of the shared and distinct features of AD and BIP

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development

The genetics of the mood disorder spectrum:genome-wide association analyses of over 185,000 cases and 439,000 controls

Background Mood disorders (including major depressive disorder and bipolar disorder) affect 10-20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Despite their diagnostic distinction, multiple approaches have shown considerable sharing of risk factors across the mood disorders. Methods To clarify their shared molecular genetic basis, and to highlight disorder-specific associations, we meta-analysed data from the latest Psychiatric Genomics Consortium (PGC) genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; non-overlapping N = 609,424). Results Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More genome-wide significant loci from the PGC analysis of major depression than bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell-types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment – positive in bipolar disorder but negative in major depressive disorder. Conclusions The mood disorders share several genetic associations, and can be combined effectively to increase variant discovery. However, we demonstrate several differences between these disorders. Analysing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum