To Örebro University

INTRODUCTION: Despite increasing numbers of working-age cancer survivors, evidence on their future work-related circumstances is limited. This study examined their future sick leave, disability pension, and unemployment benefits compared to matched cancer-free individuals.

METHODS: A matched cohort study was conducted using nationwide Swedish registers. In total, 94,411 individuals aged 25 to 59 years when diagnosed with incident cancer in 2001-2012 and who returned to work after cancer were compared with their matched cancer-free individuals (N = 354,814). Follow-up started from the year before cancer diagnosis and continued up to 14 years. Generalized estimating equations were used to calculate incidence rate ratios (IRR) and odds ratios for the difference between cancer survivors and matched cancer-free individuals.

RESULTS: Compared with cancer-free individuals, cancer survivors had six times higher sick-leave days per year after cancer (IRR 6.25 [95% CI, 5.97-6.54] for men; IRR, 5.51 [5.39-5.64] for women). This higher number of sick-leave days declined over time but a two-fold difference persisted. An approximate 1.5 times higher risk of receiving disability pension remained during follow-up. The unemployment days tended to be lower for cancer survivors (IRR, 0.84 [0.75-0.94] for men; IRR, 0.91 [0.86-0.96] for women). Risk of sick leave and disability pension was higher among those with leukemia, colorectal, and breast cancer than skin and genitourinary cancers.

CONCLUSIONS: Cancer survivors who returned to work experienced a high and persisting sick leave and disability pension for over a decade. Prolonged receipt of a high amount of benefits may have long-term adverse impacts on financial circumstances; more knowledge to promote the environment that encourages returning to and remaining in work is needed.

IMPORTANCE: Exposure to adverse childhood experiences (ACEs) has consistently been associated with multiple negative mental health outcomes extending into adulthood. However, given that ACEs and psychiatric disorders cluster within families, it remains to be comprehensively assessed to what extent familial confounding contributes to associations between ACEs and clinically confirmed adult psychiatric disorders.

OBJECTIVE: To investigate whether associations between ACEs and adult mental health outcomes remain after adjusting for familial (genetic and environmental) confounding.

DESIGN, SETTING, AND PARTICIPANTS: This Swedish twin cohort study used a discordant twin pair design based on monozygotic (MZ) and dizygotic (DZ) twins. A total of 25 252 adult twins (aged 18-47 years) from the Swedish Twin Registry born between 1959 and 1998 were followed up from age 19 years until 2016, with a maximum follow-up time of 39 years. Data were analyzed from April 2022 to November 2023.

EXPOSURES: A total of 7 ACEs, including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime, were assessed with items from the Life Stressor Checklist-Revised in a web-based survey.

MAIN OUTCOMES AND MEASURES: Adult (ages >18 years) clinical diagnosis of psychiatric disorders (ie, depressive, anxiety, alcohol or drug misuse, or stress-related disorders) were obtained from the Swedish National Patient Register.

RESULTS: Of 25 252 twins included in the study (15 038 female [59.6%]; mean [SD] age at ACE assessment, 29.9 [8.7] years), 9751 individuals (38.6%) reported exposure to at least 1 ACE. A greater number of ACEs was associated with increased odds of any psychiatric disorder in the full cohort (odds ratio [OR] per additional ACE, 1.52; 95% CI, 1.48-1.57). The association remained but ORs per additional ACE were attenuated in DZ (1.29; 95% CI, 1.14-1.47) and MZ (1.20; 95% CI, 1.02-1.40) twin pairs. Individuals who were exposed to sexual abuse compared with those who were not exposed had increased odds of any clinically confirmed psychiatric disorder in all comparisons: full cohort (OR, 3.09; 95% CI, 2.68-3.56), DZ twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and MZ twin pairs (1.80; 95% CI, 1.04-3.11).

CONCLUSIONS AND RELEVANCE: This study found that associations between ACEs and adult mental health outcomes remained after controlling for shared genetic and environmental factors, which was particularly evident after multiple ACEs or sexual abuse. These findings suggest that targeted interventions may be associated with reduced risks of future psychopathology.

OBJECTIVE: The majority of patients hospitalized for treatment of a manic episode are readmitted within 2 years despite maintenance treatment. Electroconvulsive therapy (ECT) has been associated with lower rehospitalization rates in some psychiatric conditions, but its association with readmission after a manic episode has not been investigated. Therefore, the aim of this study was to determine whether the time to readmission in patients with mania treated with ECT was longer than in patients not treated with ECT and whether there were subgroups of patients that benefited more.

METHODS: This was a nationwide register-based, observational study. All patients diagnosed with bipolar disorder, manic episode, admitted to any hospital in Sweden between 2012 and 2021 were included. Patients contributed data to the study for every admission. All admissions were followed up until psychiatric readmission, death, or the end of the study (December 31, 2021). Association between ECT and time to readmission was analyzed. A paired samples model was performed for 377 patients with at least two admissions for mania, treated with ECT at one admission and without ECT at the other admission. Times to readmission were analyzed.

RESULTS: A total of 12,337 admissions were included; mean (SD) age 47.7 (17.2), 5443 (44.1%) men. Readmission rate within 1 year was 54.6%. ECT was administered in 902 (7.3%) admissions. Within 30 days after admission, 182 out of 894 (20.4%) patients treated with ECT versus 2105 out of 11,305 (18.6%) patients treated without ECT were readmitted. There was no association between ECT and time to readmission (aHR 1.00, 95% CI 0.86-1.16, p = 0.992) in the model with all admissions. The paired samples model included 754 admissions (377 patients), mean (SD) age during admission without ECT was 45.6 (16.5), and with ECT 46.6 (16.4), 147 (39.0%) were men. In that model, readmission rate within 30 days for treatment with ECT was 19.0%, and for treatments without ECT, 24.1% (aHR 0.75, 95% CI 0.55-1.02, p = 0.067).

CONCLUSION: Readmission rates after inpatient treatment of mania were high. ECT was not significantly associated with longer time to readmission, but there was a trend toward a protective effect of ECT when admissions with and without ECT were compared within the same patients.

AIMS/HYPOTHESIS: The potential impact of childhood bereavement-a severe psychological stressor-on childhood type 1 diabetes development remains unclear. Here, we aimed to bridge this knowledge gap and assess whether bereavement characteristics influenced any impact.

METHODS: We conducted a register-based cohort study encompassing 3,598,159 children born in Sweden between 1987 and 2020. Childhood bereavement was defined as the death of a biological mother, father or sibling. Diagnosis of type 1 diabetes in childhood (<18 years) was ascertained through the National Patient Register. We applied a Cox proportional hazards regression model to investigate the impact of childhood bereavement on type 1 diabetes, while adjusting for potential confounders (including parental type 1 diabetes status, country of birth and demographic characteristics).

RESULTS: During follow-up, 86,226 children (2.4%) lost a family member, and 18,817 children (0.52%) were diagnosed with type 1 diabetes (median age at onset 9.1 years). We did not detect any overall association between childhood bereavement and type 1 diabetes (adjusted HR 1.04; 95% CI 0.93, 1.17). We found no influence of age at loss, cause of death, familial relationship to the deceased, and time since loss.

CONCLUSIONS/INTERPRETATION: In this large population-based Swedish study, we observed no evidence supporting a link between childhood bereavement and type 1 diabetes.

BACKGROUND: It has been repeatedly shown that men infected by SARS-CoV-2 face a twofold higher likelihood of dying, being hospitalized or admitted to the intensive care unit compared to women, despite taking into account relevant confounders. It has been hypothesized that these discrepancies are related to sex steroid hormone differences with estrogens being negatively correlated with disease severity. The objective of this study was therefore to evaluate COVID-19-related mortality and morbidity among peri- and postmenopausal women in relation to estrogen-containing menopause hormonal treatments (MHT).

METHODS: This is a national register-based matched cohort study performed in Sweden between January 1 to December 31, 2020. Study participants comprised women over the age of 53 years residing in Sweden. Exposure was defined as prescriptions of local estrogens, systemic estrogens with and without progestogens, progestogens alone, or tibolone. MHT users were then compared with a matched cohort of non-users. The primary outcome consisted of COVID-19 mortality, whereas the secondary outcomes included inpatient hospitalizations/outpatient visits and confirmed SARS-CoV-2 infection. Multivariable adjusted Cox regression-derived hazard ratios (HRs) were calculated.

RESULTS: Use of systemic estrogens alone is associated with increased COVID-19 mortality among older women (aHR 4.73, 1.22 to 18.32), but the association is no longer significant when discontinuation of estrogen use is accounted for. An increased risk for COVID-19 infection is further observed for women using combined systemic estrogens and progestogens (aHR 1.06, 1.00 to 1.13) or tibolone (aHR 1.21, 1.01 to 1.45). Use of local estrogens is associated with an increased risk for COVID-19-related death (aHR 2.02,1.45 to 2.81) as well as for all secondary outcomes.

CONCLUSIONS: Systemic or local use of estrogens does not decrease COVID-19 morbidity and mortality to premenopausal background levels. Excess risk for COVID-19 morbidity and mortality was noted among older women and those discontinuing systemic estrogens. Higher risk for death was also noted among women using local estrogens, for which non-causal mechanisms such as confounding by comorbidity or frailty seem to be the most plausible underlying explanations.

TRIAL REGISTRATION DETAILS: Not applicable.

BACKGROUND: Helicobacter pylori (H. pylori) is an established gastric carcinogen, also associated with an increased risk of colorectal cancer. Therefore, we suspected that H. pylori eradication lowers the risk of colorectal cancer.

MATERIAL AND METHODS: We assessed if H. pylori eradication therapy is associated with a reduced risk of colorectal adenocarcinoma in a population-based nationwide cohort study. This study included all Swedish adults with at least one recorded H. pylori eradication episode between July 2005 and December 2012, based on the high-quality Swedish health registries. Colorectal adenocarcinoma risks were compared to the Swedish background population, presented as standardized incidence ratios (SIRs) and 95% confidence intervals (CIs), accounting for age, sex, calendar period, tumor location (left or right sided), stage, and number of eradication episodes, from 1 year after eradication and onward.

RESULTS: Among 80,381 individuals receiving H. pylori eradication therapy (average follow-up 4.1 years), 282 were diagnosed with colorectal cancer (97.2% adenocarcinoma). Overall, H. pylori eradication was associated with an elevated risk of colorectal adenocarcinoma (SIR 1.27, 95% CI: 1.12-1.43). The colorectal adenocarcinoma risk was increased 1-2 years after eradication (SIR 1.42, 95% CI: 1.17-1.72), then decreased 2-4 years (SIR 0.80, 95% CI: 0.65-0.98) and 4-6 years (SIR 0.76, 95% CI: 0.57-0.99), yet not ≥ 6 years (SIR 1.36, 95% CI: 0.78-2.21) after eradication compared to the general population. Overall, right-sided (SIR 1.47, 95% CI: 1.21-1.76) and left-sided (SIR 1.35, 95% CI: 1.09-1.67) colon adenocarcinomas risks were higher among eradicated individuals than the general population.

CONCLUSION: H. pylori eradication was not associated with a clear and consistent reduction of colorectal cancer in our Swedish cohort.

Serious infections may result in greater risk of Parkinson's disease. However, high-quality cohort studies focusing on a potential causal role of different types and sites of infection are lacking. Gastrointestinal infections are of a particular interest due to growing evidence implicating gut dysbiosis in Parkinson's disease aetiology. This population-based cohort study used the Swedish Total Population Register to identify individuals born during 1944-77 and resident in Sweden between 1990 and 2018 (N = 3 698 319). Hospital-treated infections at ages 21-30 and 31-40 years were identified from the National Patient Register. Participants were followed to identify Parkinson's disease diagnoses from age 41 years up to December 31, 2018, when the oldest individual reached 75 years. Cox regression with a sibling comparison design to tackle familial genetic and environmental confounding was used to derive hazard ratios and 95% confidence intervals for each infection site, type, or any infections at ages 21-30 and 31-40 years. During a median follow-up of 15.4 years, 8815 unique Parkinson's disease diagnoses were accrued, with a crude rate of 17.3 (95% confidence interval 17.0, 17.7) per 100 000 person-years. After controlling for shared familial factors, hospital-treated gastrointestinal and respiratory infections between 21 and 30 years of age were associated with a greater risk of Parkinson's disease [hazard ratios 1.35 (95% confidence interval: 1.05, 1.75) and 1.45 (95% confidence interval: 1.08, 1.95), respectively]; no association was found for any infections at age 31-40 [hazard ratio 1.05 (95% confidence interval: 0.93, 1.19)]. After adjustment, no statistically significant associations were observed for other sites including genitourinary and skin. These findings suggest that hospital-treated infections of the gastrointestinal tract and lungs, both of which may have an influence on the gut microbiome, by age 30 years may be risk factors for Parkinson's disease.

OBJECTIVES: We aimed to evaluate the risk of colorectal adenocarcinoma (CRA) associated with long-term use of proton pump inhibitors (PPIs) in a large nationwide cohort.

DESIGN: Retrospective cohort study.

SETTING: This research was conducted at the national level, encompassing the entire population of Sweden.

PARTICIPANTS: This study utilised Swedish national registries to identify all adults who had ≥180 days of cumulative PPI use between July 2005 and December 2012, excluding participants who were followed up for less than 1 year. A total of 754 118 maintenance PPI users were included, with a maximum follow-up of 7.5 years.

INTERVENTIONS: Maintenance PPI use (cumulative≥180 days), with a comparator of maintenance histamine-2 receptor antagonist (H2RA) use.

PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the risk of CRA, presented as standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). Subgroup analyses were performed to explore the impact of indications, tumour locations, tumour stages and the duration of follow-up. A multivariable Poisson regression model was fitted to estimate the incidence rate ratios (IRRs) and 95% CIs of PPI versus H2RA use.

RESULTS: Maintenance PPI users exhibited a slightly elevated risk of CRA compared to the general population (SIR 1.10, 95% CI=1.06 to 1.13) for both men and women. Individuals aged 18-39 (SIR 2.79, 95% CI=1.62 to 4.47) and 40-49 (SIR 2.02, 95% CI=1.65 to 2.45) had significantly higher risks than the general population. Right-sided CRA showed a higher risk compared to the general population (SIR 1.26, 95% CI=1.20 to 1.32). There was no significant difference in the risk of CRA between maintenance PPI users and maintenance H2RA users (IRR 1.05, 95% CI=0.87 to 1.27, p<0.05).

CONCLUSIONS: Maintenance PPI use may be associated with an increased risk of CRA, but a prolonged observation time is needed.

Demyelinating diseases including multiple sclerosis are associated with prior infectious exposures, so we assessed whether SARS-CoV-2 infection is associated with subsequent diagnoses of non-multiple sclerosis demyelinating diseases and multiple sclerosis. All residents of Sweden aged 3-100 years were followed between 1 January 2020 and 30 November 2022, excluding those with demyelinating disease prior to 2020, comprising 9 959 818 individuals divided into uninfected and those who were infected were categorized into those with and without hospital admission for the infection as a marker of infection severity. Cox regression assessed the risk of two separate outcomes: hospital diagnosed non-multiple sclerosis demyelinating diseases of the CNS and multiple sclerosis. The exposures were modelled as time-varying covariates (uninfected, infection without hospital admission and infected with hospital admission). Hospital admission for COVID-19 was associated with raised risk of subsequent non-multiple sclerosis demyelinating disease, but only 12 individuals had this outcome among the exposed, and of those, 7 has an unspecified demyelinating disease diagnosis. Rates per 100 000 person-years (and 95% confidence intervals) were 3.8 (3.6-4.1) among those without a COVID-19 diagnosis and 9.0 (5.1-15.9) among those admitted to hospital for COVID-19, with an adjusted hazard ratio and (and 95% confidence interval) of 2.35 (1.32-4.18, P = 0.004). Equivalent associations with multiple sclerosis (28 individuals had this outcome among the exposed) were rates of 9.5 (9.1-9.9) and 21.0 (14.5-30.5) and an adjusted hazard ratio of 2.48 (1.70-3.61, P < 0.001). Only a small number of non-multiple sclerosis demyelinating disease diagnoses were associated with hospital admission for COVID-19, and while the number with multiple sclerosis was somewhat higher, longer duration of follow-up will assist in identifying whether the associations are causal or due to shared susceptibility or surveillance bias, as these diseases can have long asymptomatic and prodromal phases.

BACKGROUND: The psychological toll on parents of a child receiving a cancer diagnosis is known to be high, but there is a knowledge gap regarding suicidal behavior among these parents. The aim of this study was to investigate the risk of suicide attempt and death by suicide in relation to having a child with cancer.

METHODS AND FINDINGS: We performed a binational population-based and sibling-controlled cohort study, including all parents with a child diagnosed with cancer in Denmark (1978 to 2016) or Sweden (1973 to 2014), 10 matched unexposed parents per exposed parent (population comparison), and unaffected full siblings of the exposed parents (sibling comparison). Suicide attempt was identified through the Patient Register and the Psychiatric Central Register in Denmark and the Patient Register in Sweden, whereas death by suicide was identified through the Danish Causes of Death Register and the Swedish Causes of Death Register. In population comparison, we used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of suicide attempt and death by suicide associated with cancer diagnosis of a child, adjusting for sex, age, country of residence, calendar year, marital status, highest attained educational level, household income, history of cancer, history of psychiatric disorder, and family history of psychiatric disorder. The sibling comparison was performed to assess the role of familial confounding in the studied associations. The population comparison consisted of 106,005 exposed parents and 1,060,050 matched unexposed parents, with a median age of 56 at cohort entry and 46.9% male. During the median follow-up of 7.3 and 7.2 years, we observed 613 (incidence rate [IR], 58.8 per 100,000 person-years) and 5,888 (IR, 57.1 per 100,000 person-years) cases of first-onset suicide attempt among the exposed and unexposed parents, respectively. There was an increased risk of parental suicide attempt during the first years after a child's cancer diagnosis (HR, 1.15; 95% CI, [1.03, 1.28]; p = 0.01), particularly when the child was 18 or younger at diagnosis (HR, 1.25; 95% CI, [1.08, 1.46]; p = 0.004), when the child was diagnosed with a highly aggressive cancer (HR, 1.60; 95% CI, [1.05, 2.43]; p = 0.03), or when the child died due to cancer (HR, 1.63; 95% CI, [1.29, 2.06]; p < 0.001). The increased risk did not, however, maintain thereafter (HR, 0.86; 95% CI: [0.75, 0.98]; p = 0.03), and there was no altered risk of parental death by suicide any time after the child's cancer diagnosis. Sibling comparison corroborated these findings. The main limitation of the study is the potential residual confounding by factors not shared between full siblings.

CONCLUSIONS: In this study, we observed an increased risk of parental suicide attempt during the first years after a child's cancer diagnosis, especially when the child was diagnosed during childhood, or with an aggressive or fatal form of cancer. There was, however, no altered risk of parental death by suicide at any time after a child's cancer diagnosis. Our findings suggest extended clinical awareness of suicide attempt among parents of children with cancer, especially during the first few years after cancer diagnosis.