In-patient psychiatric care and non-substance-related psychiatric diagnoses among individuals seeking treatment for alcohol and substance use disorders: associations with all-cause mortality and suicide.

BACKGROUND: The largest excess mortality risk has been reported for combinations of psychiatric disorders that included substance use disorders. AIMS: To study the associations of different non-substance-related in-patient psychiatric diagnoses with all-cause mortality and suicide up to 28 years of age after entering substance use treatment. METHOD: National register data on psychiatric hospital admissions and death were combined with the treatment records of over 10 000 individuals in substance use treatment between 1990 and 2009. Cox regression was used to calculate hazard ratios (HRs) with 95% CIs for all-cause and suicide-specific mortality from the time of entering substance use treatment. RESULTS: Nearly one-third (31.4%; n = 3330) of the study population had died during follow-up or by their 65th birthday, with more than one in ten (n = 385) from suicide. Over half of the study population (53.2%) had undergone psychiatric in-patient care and 14.1% involuntary psychiatric care during the study period. Bipolar disorder and unipolar depression were associated with a 57% (HR 1.57, 95% CI 1.18-2.10) and 132% (HR 2.32, 95% CI 1.21-4.46) increase in risk of suicide, respectively. Involuntary psychiatric care was associated with a 40% increase in risk of suicide (HR 1.42, 95% CI 1.05-1.94). CONCLUSION: Severe psychiatric morbidity is common among individuals seeking treatment for alcohol and/or substance use and specifically mood disorders appear to increase the risk of suicide. Treatment service planning needs to focus on integrated care for concomitant substance use and psychiatric disorders to address this risk.

Exome-wide somatic mutation characterization of small bowel adenocarcinoma.

Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. Despite previous studies, its molecular genetic background has remained somewhat elusive. To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. Archival tissue from 106 primary tumors with appropriate clinical information were available for exome sequencing from a patient series consisting of a majority of confirmed SBA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify driver genes from the exome data. We also defined frequently affected cancer signalling pathways and performed the first extensive allelic imbalance (AI) analysis in SBA. Exome data analysis revealed significantly mutated genes previously linked to SBA (TP53, KRAS, APC, SMAD4, and BRAF), recently reported potential driver genes (SOX9, ATM, and ARID2), as well as novel candidate driver genes, such as ACVR2A, ACVR1B, BRCA2, and SMARCA4. We also identified clear mutation hotspot patterns in ERBB2 and BRAF. No BRAF V600E mutations were observed. Additionally, we present a comprehensive mutation signature analysis of SBA, highlighting established signatures 1A, 6, and 17, as well as U2 which is a previously unvalidated signature. Finally, comparison of the three small bowel segments revealed differences in tumor characteristics. This comprehensive work unveils the mutational landscape and most frequently affected genes and pathways in SBA, providing potential therapeutic targets, and novel and more thorough insights into the genetic background of this tumor type.

Imprisonment, community sanctions and mortality by cause of death among patients with substance use disorder - a 28-year follow-up using Finnish register data.

BACKGROUND: The first few weeks' post-imprisonment are associated with high mortality, particularly among individuals with a history of substance use. Excess risk may vary by societal context due to a range of penal systems and substance use patterns. Using data on Finnish individuals who had sought treatment for substance use, we studied the association between criminal sanctions with cause-specific mortality. METHODS: The database contained 10887 individuals who had sought treatment between 1990 and 2009. Their treatment data were combined with register data on imprisonments and community sanctions and weekly mortality between 1992 and 2015. Mortality was analysed using discrete-time survival models. We controlled for age and sociodemographic factors, and analysed whether education, type of substance used and the type of latest sentence modified the associations. FINDINGS: Mortality was high in the first two weeks after sanctions (all-cause odds ratio [OR] 2.61, 95% confidence interval [CI] 1.67-4.07; drug-related deaths OR 8.52, 95% CI 4.64-15.7). Excess risk declined over time (OR after 12 weeks: 1.19, 95% CI 1.07-1.31). Most of the excess risk was attributable to external causes. Mortality was low during imprisonment, but not during community sanctions. The patterns were similar by level of education, substance use and the type of latest sentence. CONCLUSIONS: Community sanctions were not associated with mortality among people with substance use disorders. Mortality was low during imprisonment, but high post-release. Criminal sanctions should be better utilised as intervention touchpoints and follow-up resources should target prisoners with substance use treatment history to reduce post-release mortality.