Swedish National Registers Research Articles

Death of parent, sibling, spouse, and child in a Swedish national sample and risk of subsequent stress reaction, major depression, alcohol-use disorder, and drug-use disorder.

To determine, in a general population, how much rates of stress reactions (SR), major depression (MD), alcohol-use disorder (AUD) and drug-use disorder (DUD) increase after the death of close relatives. SR, MD, AUD, and DUD registrations were assessed from national Swedish registries. From the population followed from 2000 to 2018, those exposed to death of a close relative in 2002-2016 were matched to unexposed controls and analyzed in males and females by a controlled pre-post design using a difference-in-difference method. Substantial, brief increases in risk for SR and more modest prolonged increases in MD were observed after death of relatives in both men and women greatest with children, followed by spouses, parents, and siblings. Relatively long-lasting modest increases in AUD but not DUD were also observed following death of relatives. The absolute increases for SR and MD were greater in females than males and for AUD greater in males than females. However, logistic regression analyses showed most effects did not differ significantly by sex. Consistently larger increases in disorder risk were seen with the death of younger v. older parents, siblings, and spouses and with accidental v. non-accidental death in children. Applying a matched cohort design to Swedish population registries, death of close relatives was associated with, and likely caused, substantial increases in rates of SR, MD, and AUD, consistent with smaller prior clinical investigations. Through such registries, we can, in large representative samples, integrate the impact of exposures to selected environmental adversities into disorder risk pathways.

Incidence, demographics and rehabilitation after digital nerve injury: A population-based study of 1004 adult patients in Sweden.

The main objective of this study was to describe the epidemiology of surgically repaired digital nerve injuries in a Swedish population. Secondary objectives were to describe the demographics of the patient population, injury characteristics, post-operative care and rehabilitation. From 2012 to 2018, 1004 patients with a surgically repaired digital nerve injury resident in the Stockholm region were identified in the Swedish national quality registry for hand surgery and all medical records were thoroughly reviewed. The incidence rate was 8.3 per 100.000 person-years and these injuries were more common in men than women. The median age at the time of injury was 37 years and a sharp cut was the most common mechanism of injury. Injuries were equally distributed over weekdays and the year, but surgery was most often performed on Mondays. There were no differences in treatment and rehabilitation regimens between sexes, except women were more likely than men to be operated within three days from injury. Timing and content of rehabilitation varied largely between individuals. One third of patients did not receive any sensory relearning and sensory assessment was performed in only 7%. The epidemiology shows no major changes over the last decade. However, we found a large individual variation in follow up visits, rehabilitation content and assessments indicating large differences in consumption of health care resources. Our findings expose the need to further improve and evaluate rehabilitation regimens after digital nerve injury.

Abstract 6474: Stress-related sick leave and subsequent cancer risk: A Swedish national register study of 516 678 cancer cases

Abstract Background: Despite previous studies investigating psychological stress in relation to cancer risk, no consensus has been reached as to whether stress is a modifiable risk factor for cancer. This study aims to investigate whether sick leave due to psychological stress can affect the risk of developing cancer. Method: This is a matched case-control study using Swedish nation-wide register data (study period 2005-2018). The main exposure is stress-related sick leave defined as registered sick leave due to psychological stress with the diagnosis codes of F43 (International Classification of Diseases codes: ICD) and its subclassifications and hereafter referred to as stress leave. For each primary cancer case (except non-melanoma skin cancer), up to five cancer-free controls were matched based on sex, age and county. Conditional logistic regression, conditioned on matching factors and adjusting for socioeconomic factors, was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). For subgroup analyses by specific tumor sites, Bonferroni-corrected significance level of 0.002 (alpha value divided by the number of tumor sites = 0.05/24) was also applied. Results: The study comprised 516 678 cancer cases and 2 357 433 matched controls. Stress leave of any duration, was associated with a modestly increased risk of cancer, with the highest risk observed for 1-30 days of leave, vs no leave during follow-up (adjusted OR 1.05, 95% CI 1.02-1.09). In subgroup analyses by tumor sites, stress leave was associated with an increased risk of prostate cancer (adjusted OR for >90 days vs no stress leave 1.10, 95% CI 1.01-1.20) and cervix cancer (adjusted OR>90 days vs no leave 1.11, 95% CI 1.05-1.17). For lung cancer, an inverse risk relationship was found (adjusted OR>90 days vs no leave 0.88, 95% CI 0.77-0.99). For other tumor sites, associations were generally null or had wide confidence intervals. After applying a Bonferroni-corrected significance level, the association was still significant for cervical cancer. Further examination by sex, specific types of psychological stress and cancer groups based on established etiology (tobacco use, obesity, alcohol consumption and gastric hyperacidity) showed a clear exposure-response trend in men and pronounced associations for exhaustion disorder (ICD code: F43.8A) and tobacco-related cancers. In a post-hoc analysis, the association for other HPV-related cancers was similar to that for cervical cancer but not statistically significant. Conclusion: In this register study covering the entire Swedish population, we found that stress-related sick leave was associated with modestly higher risk of cancer, particularly the risk of cervical cancer. Potential higher risk of prostate cancer and lower risk of lung cancer were observed, though these associations were not statistically significant after controlling for multiple testing. Citation Format: Sai San Moon Lu, Jenny Hadrévi, Lisbeth Slunga Järvholm, Florentin Späth, Richard Palmqvist, Tommy Olsson, Sophia Harlid, Bethany van Guelpen. Stress-related sick leave and subsequent cancer risk: A Swedish national register study of 516 678 cancer cases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6474.

Patient-reported outcome measures and their association to the original Strickland classification after flexor tendon repair.

The aim of this study was to examine the relationship between patient-reported outcome measures (PROMs) and the original Strickland classification after flexor tendon injuries in Zones 1 and 2. Data were collected from the Swedish national health care registry for hand surgery (HAKIR). The studied PROMs were the Quick Disabilities of Arm, Shoulder and Hand (QuickDASH) and the patient questionnaire from the HAKIR (HQ-8). Complete data of both range of motion (ROM) and PROMs were available for 215 patients at 3 months after surgery, and for 150 patients at 12 months after surgery. We found that QuickDASH values were low and similar between all groups as classified by the Strickland system at 12 months. A statistically significant difference between PROM values (for stiffness and satisfaction) was found only between the Strickland groups Fair and Good, but not between Poor and Fair or Good and Excellent. This suggests that further categorization according to the Strickland classification is less important to the patients as long as they regain 70% of their ROM.Level of evidence: III.

Explaining COVID-19 mortality among immigrants in Sweden from a social determinants of health perspective (COVIS): protocol for a national register-based observational study

IntroductionAdopting a social determinants of health perspective, this project aims to study how disproportionate COVID-19 mortality among immigrants in Sweden is associated with social factors operating through differential exposure to...

Changes in parents' mental health related to child out-of-home care placements: A Swedish national register study

BackgroundLiterature on outcomes of children in out-of-home care (OHC) is extensive. However, less is known regarding associations of such placements with parental mental health disorders (MHD). ObjectiveThis study investigated changes in hospitalization rates due to MHD among parents, four years before and after placement of their child in OHC. Participants and settingWe used data on 4067 members (Generation 1) of the RELINK53 cohort (individuals born and living in Sweden in 1953) and their 5373 children (Generation 2) in OHC. MethodsUsing random effects regression models, associations between OHC and MHD were examined separately for fathers and mothers. Nested models were tested exploring associations with parent and child/placement-related factors. Marginal effects were computed to assess mean rates of hospitalization annually. ResultsOverall, mothers had higher mean hospitalization rates than fathers. Compared to the year of placement, hospitalization rates were significantly lower in the four years before placement for mothers (9.9 %, 9.5 %, 10.5 %, 12.1 %, respectively) and fathers (5.9 %, 7.6 %, 8 %, 9.8 %, respectively). Mothers showed highest hospitalization rates at the year of placement (26.6 %), while fathers, one year after placement (13.4 %). Hospitalization rates declined significantly directly after placement among mothers, but an unclear and non-significant pattern of results was found among fathers. ConclusionsMost parents have higher hospitalization rates at and directly after placement. Potential hypotheses underlying these findings are discussed, including psychosocial gender differences and opportunities to seek care as means of reunification. There is an urgency to develop strategies to better support these parents throughout the process.

VAI-B: a multicenter platform for the external validation of artificial intelligence algorithms in breast imaging.

Multiple vendors are currently offering artificial intelligence (AI) computer-aided systems for triage detection, diagnosis, and risk prediction of breast cancer based on screening mammography. There is an imminent need to establish validation platforms that enable fair and transparent testing of these systems against external data. We developed validation of artificial intelligence for breast imaging (VAI-B), a platform for independent validation of AI algorithms in breast imaging. The platform is a hybrid solution, with one part implemented in the cloud and another in an on-premises environment at Karolinska Institute. Cloud services provide the flexibility of scaling the computing power during inference time, while secure on-premises clinical data storage preserves their privacy. A MongoDB database and a python package were developed to store and manage the data on-premises. VAI-B requires four data components: radiological images, AI inferences, radiologist assessments, and cancer outcomes. To pilot test VAI-B, we defined a case-control population based on 8080 patients diagnosed with breast cancer and 36,339 healthy women based on the Swedish national quality registry for breast cancer. Images and radiological assessments from more than 100,000 mammography examinations were extracted from hospitals in three regions of Sweden. The images were processed by AI systems from three vendors in a virtual private cloud to produce abnormality scores related to signs of cancer in the images. A total of 105,706 examinations have been processed and stored in the database. We have created a platform that will allow downstream evaluation of AI systems for breast cancer detection, which enables faster development cycles for participating vendors and safer AI adoption for participating hospitals. The platform was designed to be scalable and ready to be expanded should a new vendor want to evaluate their system or should a new hospital wish to obtain an evaluation of different AI systems on their images.

Risk for psychiatric and substance use disorders as a function of transitions in Sweden's public educational system: a national study.

To clarify, in a national sample, associations between risk for seven psychiatric and substance use disorders and five key transitions in Sweden's public educational system. Swedish-born individuals (1972-1995, N = 1 997 910) were followed through 12-31-2018, at mean age 34.9. We predicted, from these educational transitions, risk for major depression (MD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), anorexia nervosa (AN), alcohol use disorder (AUD), and drug use disorder (DUD), assessed from Swedish national registers, by Cox regression, censoring individuals with onsets ⩽17. We also predicted risk from the deviation of grades from family-genetic expectations (deviation 1) and from changes in grades from ages 16 to 19 (deviation 2). We observed four major risk patterns across transitions in our disorders: (i) MD and BD, (ii) OCD and SZ, (iii) AUD and DUD, and (iv) AN. Failing early educational transitions had the greatest impact on risk for OCD and SZ while for other disorders, not progressing from basic to upper high school had the largest effect. Completing vocational v. college-prep upper high school was strongly associated with risk for AUD and DUD, had little relation with MD, OCD, BD, and SZ risk, and was protective for AN. Deviation 1 predicted risk most strongly for SZ, AN, and MD. Deviation 2 predicted risk most strongly for SZ, AUD, and DUD. The pattern of educational transitions and within family and within person development deviations are strongly and relatively specifically associated with future risk for seven psychiatric and substance-use disorders.

Overweight in childhood and young adulthood increases the risk for adult thromboembolic events.

Approximately one third of thromboembolic (TE) events are related to obesity, but to which extent elevated body mass index (BMI) during the distinct periods of childhood and puberty contributes is not known. We aimed to evaluate the impact of high BMI during childhood and puberty for the risk of adult venous and arterial thromboembolic events (VTE, ATE, respectively) in men. We included 37,672 men from the BMI Epidemiology Study (BEST) Gothenburg with data on weight and height in childhood, young adult age, and on pubertal BMI change. Information on outcomes (VTE [n=1683], ATE [n=144], or any first TE event [VTE or ATE; n=1780]) was retrieved from Swedish national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions. Both BMI at 8 years of age and the pubertal BMI change were associated with VTE, independently of each other (BMI at 8: HR 1.06 per standard deviation [SD] increase, 95% CI, 1.01;1.11; pubertal BMI change: HR 1.11 per SD increase, 95% CI, 1.06;1.16). Individuals with normal weight during childhood followed by young adult overweight (HR 1.40, 95% CI, 1.15;1.72), and individuals with overweight at both childhood and young adult age (HR 1.48, 95% CI, 1.14;1.92), had a significantly increased risk of VTE in adult life, compared with the normal weight reference group. Individuals with overweight in childhood and in young adult age had increased risk of ATE and TE. Young adult overweight was a strong determinant, and childhood overweight a moderate determinant, of the risk of VTE in adult men.

Myopia in late adolescence and subsequent multiple sclerosis among men.

Risk factors such as low vitamin D level has been implicated in the etiology of multiple sclerosis (MS) and may be relevant to myopia, such that there may be an association between myopia and MS. Using linked Swedish national register data, we conducted a cohort study of men who were born in Sweden between 1950 and 1992, lived in Sweden between 1990 and 2018, and enrolled in military conscription assessment (n=1,847,754). Myopia was defined based on the spherical equivalent refraction measured at conscription assessment, around age 18 years. Multiple sclerosis was identified using the Patient Register. Cox regression produced hazard ratios (HR) with 95% confidence intervals (95% CI), with adjustment for demographic and childhood socioeconomic characteristics and residential region. Due to changes in the assessment of refractive error, the analysis was stratified into two groups by the year of conscription assessment: 1969-1997 and 1997-2010. Among 1,559,859 individuals during a maximum of 48 years of follow-up from age 20 to 68 years (44,715,603 person-years), there were 3,134 MS events, and the incidence rate 7.0 (95% CI [6.8, 7.3] per 100,000 person-years). Among individuals with conscription assessments during 1997-2010, there were 380 MS events. There was no evidence of an association between myopia and MS, with HR 1.09 (95% CI 0.83, 1.43). Among individuals who underwent conscription assessment in 1969-1997, there were 2754 MS events. After adjusting for all covariates, there was no evidence of an association between myopia and MS (HR 0.99 [95% CI 0.91, 1.09]). Myopia in late adolescence is not associated with a subsequent raised risk of MS and thus there does not appear to be important shared risk factors.

Improved survival after laparoscopic compared to open gastrectomy for advanced gastric cancer: a Swedish population-based cohort study

BackgroundLaparoscopic gastrectomy is increasingly used for the treatment of locally advanced gastric cancer but concerns remain whether similar results can be obtained compared to open gastrectomy, especially in Western populations. This study compared the short-term postoperative, oncological and survival outcomes following laparoscopic versus open gastrectomy based on data from the Swedish National Register for Esophageal and Gastric Cancer.MethodsPatients who underwent surgery with curative intent for adenocarcinoma of the stomach or gastroesophageal junction Siewert type III from 2015 to 2020 were identified, and 622 patients with cT2-4aN0-3M0 tumors were included. The impact of surgical approach on short-term outcomes was assessed using multivariable logistic regression. Long-term survival was compared using multivariable Cox regression.ResultsIn total, 350 patients underwent open and 272 laparoscopic gastrectomy, of which 12.9% were converted to open surgery. The groups were similar regarding distribution of clinical disease stage (27.6% stage I, 46.0% stage II, and 26.4% stage III). Neoadjuvant chemotherapy was administered to 52.7% of the patients. There was no difference in the rate of postoperative complications, but laparoscopic approach was associated with lower 90 day mortality (1.8 vs 4.9%, p = 0.043). The median number of resected lymph nodes was higher after laparoscopic surgery (32 vs 26, p < 0.001), while no difference was found in the rate of tumor-free resection margins. Better overall survival was observed after laparoscopic gastrectomy (HR 0.63, p < 0.001).ConclusionsLaparoscopic gastrectomy can be safely preformed for advanced gastric cancer and is associated with improved overall survival compared to open surgery.

Risk of dementia and mild cognitive impairment in older adults with a criminal background: a population-based register study in Sweden

Criminal behaviour has previously been associated with an increased risk for several mental health problems, but little is known about the association between criminal behaviour and dementia. We aimed to examine how the criminal background (type of crime, number of convictions, length of the sentence) is associated with dementia and mild cognitive impairment (MCI), and how mental and physical health disorders and educational attainment influenced these associations. A nationwide cohort of 3,617,028 individuals born between 1932 and 1962 were linked with criminal and medical records using Swedish national registers. We used Cox regression models to examine the associations. Increased risks for dementia (Hazard ratios (HRs) 1.54, 95% confidence interval (CI) 1.50–1.57) and MCI (1.55, 1.50–1.61) were found in individuals with criminal background, particularly among those who committed violent or several crimes, or with long sentences. After full adjustment of covariates, the associations attenuated but remained statistically significant for dementia (1.25, 1.22–1.28) and MCI (1.27, 1.22–1.32). The attenuation was mostly explained by mental health problems -depression, anxiety, schizophrenia spectrum disorders, substance use disorder (SUD), and bipolar disorder- (dementia: 1.34, 1.31–1.37; MCI: 1.35, 1.30–1.40). SUD contributed the most to attenuate the associations. Our results may provide important insights to health and penal systems by showing the importance of considering the severity of the criminal background and life-course mental health when assessing the risk of neurodegenerative disorders.

Preoperative upper tract invasive diagnostic modalities are associated with intravesical recurrence following surgery for upper tract urothelial carcinoma: A population-based study.

Intravesical recurrence (IVR) after surgery for upper tract urothelial carcinoma (UTUC) is a clinical problem. We investigated if preoperative invasive diagnostic modalities (IDM) such as antegrade/retrograde uretero-pyelography and/or selective urine cytology/barbotage, and URS with or without concomitant biopsy are associated with IVR after radical surgery for UTUC. Risk of death from urothelial cancer and all causes was investigated as secondary outcomes. We investigated a population-based cohort of 1038 consecutive patients subjected to radical surgery for UTUC 2015-2019 in Sweden, using the Bladder Cancer Data Base Sweden (BladderBaSe 2.0), comprising all patients in the Swedish National Registry of Urinary Bladder Cancer. Risk estimates of IVR, death from urothelial cancer, and all causes was assessed using multivariable Cox regression models. The study included 536 cases with and 502 without preoperative IDM. IDM was associated with increased risk of IVR (HR 1.24, 95% CI 1.03-1.52) and risk of urothelial cancer death (HR 1.56, CI 1.12-2.18), compared to no IDM after a median follow-up of 1.3 yrs. Stratified analysis for tumor location showed that IDM was associated with risk of IVR in ureteric cancer (HR 1.66, 95% CI 1.21-2.28) but not in renal pelvic cancer (HR 1.07, 95% CI 0.81-1.41). Limitations included the observational setting and the lack of variables such as tumour grade, multifocality and preoperative hydronephrosis. Worse outcomes for patients subjected to preoperative IDM highlight the need for carefully considering diagnostic decisions for UTUC patients, specifically in tumours located in the ureter.

Examining common and distinct contributions to the etiology of suicide attempt and reattempt.

This study examined the extent to which the genetic and environmental characteristics of having a first versus a second suicide attempt (SA) are common or specific. We evaluated the direct pathway between these phenotypes and the role of specific risk factors. From Swedish national registries, two subsamples of individuals born between 1960 and 1980 were selected (1,227,287 twin-sibling pairs and 2,265,796 unrelated individuals). First, a twin-sibling model was fit to evaluate the genetic and environmental risk factors related to first and second SA. The model also included a direct path between first and second SA. Second, an extended Cox proportional hazards model (PWP) was used to evaluate the risk factors related to first versus second SA. In the twin-sibling model, suicide reattempt was strongly related to first SA (β = 0.72). The total heritability for the second SA was estimated at 0.48, with 45.80% unique to this second SA. The total environmental influence for the second SA was 0.51, with 50.59% unique. In the PWP model, we found that childhood environment, psychiatric disorders, and selected stressful life events were related to both first and second SA, potentially reflecting common genetic and environmental factors. Other stressful life events were associated with first but not second SA in the multivariable model, suggesting their specificity in explaining the first occurrence of SA but not its recurrence. Specific risk factors related to second SA need to be further explored. These findings have important implications for describing the pathways toward suicidal behavior and identifying individuals at risk for multiple SA. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Ophthalmological outcome of 6.5 years children treated for retinopathy of prematurity: a Swedish register study

AimsTo determine the ophthalmological outcome at 6.5 years of age in children treated for retinopathy of prematurity (ROP), and registered in the national Swedish National Register for ROP register.MethodsData on...

COVID-19 and comedications in atrial fibrillation—a case–control study in Stockholm

To test the main hypothesis that anticoagulation reduces risk of hospitalization, intensive care unit (ICU) admission and death in COVID-19. Nested case–control study among patients with atrial fibrillation (AF) in Stockholm. COVID-19 cases were matched to five disease-free controls with same sex, born within ± 1 years. Source population was individuals in Stockholm with AF 1997–2020. Swedish regional and national registers are used. National registers cover hospitals and outpatient clinics, local registers cover primary care. Records were linked through the personal identity number assigned to each Swedish resident. Cases were individuals with COVID-19 (diagnosis, ICU admission, or death). The AF source population consisted of 179,381 individuals from which 7548 cases were identified together with 37,145 controls. The number of cases (controls) identified from hospitalization, ICU admission or death were 5916 (29,035), 160 (750) and 1472 (7,360). The proportion of women was 40% for hospitalization and death, but 20% and 30% for admission to ICU in wave one and two, respectively. Primary outcome was mortality, secondary outcome was hospitalization, tertiary outcome was ICU admission, all with COVID-19. Odds ratios (95% confidence interval) for antithrombotics were 0.79 (0.66–0.95) for the first wave and 0.80 (0.64–1.01) for the second wave. Use of anticoagulation among patients with arrythmias infected with COVID-19 is associated with lower risk of hospitalization and death. If further COVID-variants emerge, or other infections with prothrombotic properties, this emphasize need for physicians to ensure compliance among vulnerable patients.

Multifaceted determinants of social-emotional problems in preschool children in Sweden: An ecological systems theory approach

Social-emotional problems occurring early in life can place children at future risk of adverse health, social and economic outcomes. Determinants of social-emotional problems are multi-layered and originate from different contexts surrounding children, though few studies consider them simultaneously. We adopted a holistic approach by using Bronfenbrenner's process-person-context-time model as a structuring device. We aimed to assess what characteristics of families and children from pregnancy, over birth, and up to 3 years of age are associated with social-emotional problems in boys and girls. This study used regional data from the Salut Programme, a universal health promotion programme implemented in Antenatal and Child Health Care, and data from national Swedish registers. The study population included 6033 3-year-olds and their parents during the period 2010–2018. Distinct logistic regression models for boys and girls were used to assess associations between the family social context, parents' lifestyle, parent's mental health, children's birth characteristics, and indicators of proximal processes (the independent variables); and children's social-emotional problems as measured by the parent-completed Ages and Stages Questionnaire: Social-Emotional between 33 and 41 months of age (the outcome). Overall, a less favourable family social context, detrimental lifestyle of the parents during pregnancy, and parents' mental illness from pregnancy onwards were associated with higher odds of social-emotional problems in 3-year-olds. Higher screentime and infrequent shared book-reading were associated with higher odds of social-emotional problems. The multifaceted determinants of children's social-emotional problems imply that many diverse targets for intervention exist. Additionally, this study suggests that Bronfenbrenner's process-person-context-time theoretical framework could be relevant for public health research and policy.

Military service and risk of subsequent drug use disorders among Swedish men.

Environmental factors contribute substantially to risk for drug use disorders (DUD). The current study applies multiple methods to empirically test whether military service is associated with subsequent DUD, as previous findings are inconsistent. Longitudinal Swedish national registry data on a cohort of male conscripts born 1972-1987 (maximum N = 485,900) were used to test the association between military service and subsequent registration for DUD. Cox proportional hazard models were used in preliminary analyses, followed by three methods that enable causal inference: propensity score models, co-relative models, and instrumental variable analysis. Across all methods, military service was causally associated with lower risk of DUD. Hazard ratios ranged from HR = 0.43 (95% confidence intervals [CI] 0.37; 0.50) in the instrumental variable analysis to 0.77 (0.75; 0.79) in the multivariate propensity score matching analysis. This effect diminished across time. In the model including a propensity score, HRs remained below 1 across the observation period, while confidence intervals included 1 after ~ 11years in the co-relative analysis and after ~ 21years in the instrumental variable analysis. In this cohort of Swedish men, complementary methods indicate that military service conferred substantial but time-limited protection against subsequent DUD. The observed effect could be due to reduced opportunity for substance use during service, social cohesion experienced during and after service, and/or socioeconomic advantages among veterans. Additional research is necessary to clarify these protective mechanisms and determine how other environmental contexts can provide similar benefits.

Direct oral anticoagulants versus warfarin in patients with non-valvular atrial fibrillation and CKD G3-G5D.

The use of direct oral anticoagulants (DOAC) in patients with non-valvular atrial fibrillation (NVAF) and advanced chronic kidney disease (CKD) including dialysis is growing. Several studies have shown favorable results of DOAC compared with warfarin regarding bleeding risk but no difference in stroke protection. However, these studies had poor time in therapeutic range (TTR), in the warfarin comparison group. This was a Swedish national cohort study investigating the risk of ischemic stroke and major bleeding on DOAC compared with warfarin in patients with NVAF, glomerular filtration rate category 3-5D (G3-G5D), kidney transplant recipients excluded, between 2009 and 2018. Data extracted from high-quality national healthcare registries including the Swedish Renal Registry, AuriculA (the Swedish national quality register for AF and anticoagulation) and The Stroke Register. At enrolment, of 2453 patients 59% were treated with warfarin (mean TTR 67%) and 41% with DOAC. Overall, 693 (28.3%) had G3, 1113 (45.4%) G4, 222 (9.1%) G5 and 425 (17.3%) G5D. DOAC compared with warfarin showed lower hazard of major bleeding [hazard ratio 0.71 (95% confidence interval 0.53-0.96)] but no difference in ischemic stroke risk. Mortality was increased during DOAC treatment [1.24 (1.01-1.53)], presumably not a causal association since fewer fatal bleedings occurred on DOAC. DOAC treatment, compared with warfarin, is associated with almost 30% lower risk of bleeding in patients with NVAF and CKD G3-G5D. The stroke risk is comparable between the treatments. This is the first study comparing DOAC and well-managed warfarin (TTR 67%) in advanced CKD. Ongoing and planned randomized controlled trials need to confirm the possible benefit of DOAC.

Testing Phenotypic Models of Posttraumatic Stress Disorder and Alcohol Use Disorder Comorbidity Using Longitudinal Registry Data.

Two predominant phenotypic models of causality exist to explain the high co-occurrence of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD): the self-medication and susceptibility models. Population-based longitudinal studies that simultaneously examine both models are needed. Thus, the goal of the present study is to test these models using the Swedish National Registries. Registries were used to conduct longitudinal Cox proportional hazard models (n ≈ 1.5 million) and cross-lagged panel models (N ≈ 3.8 million) with follow-up periods of ~23 years. Covarying for cohort and socioeconomic status, Cox proportional hazards model results found strong support for the self-medication model. Results showed that PTSD predicted increased risk for AUD among both men (HR = 4.58 [4.42, 4.74]) and women (HR = 4.14 [3.99, 4.30]), significantly more so for men (interaction HR = 1.11 [1.05, 1.16]). Support was also found for the susceptibility model, although the effects were lower in magnitude than those for the self-medication model. AUD increased risk for PTSD among men (HR = 2.53 [2.47, 2.60]) and women (HR = 2.06 [2.01, 2.12]), and significantly more so for men (interaction term HR = 1.23 [1.18, 1.28]). Cross-lagged model results of simultaneously testing both models found support for bidirectionality. The PTSD-to-AUD paths and the AUD-to-PTSD paths were of modest effect for men and women. The results from both complementary statistical approaches demonstrate that the models of comorbidity are not mutually exclusive. Although the Cox model results evidenced more support for the self-medication pathway, the cross-lagged model results suggest that the prospective relationships between these disorders are nuanced across development.