Unnur Valdimarsdóttir

One of the questions faced by the parents of a child who is terminally ill with a malignant disease is whether or not they should talk about death with their child.In 2001, we attempted to contact all parents in Sweden who had lost a child to cancer between 1992 and 1997. Among 561 eligible parents, 449 answered a questionnaire, and 429 stated whether or not they had talked about death with their child.None of the 147 parents who talked with their child about death regretted it. In contrast, 69 of 258 parents (27 percent) who did not talk with their child about death regretted not having done so. Parents who sensed that their child was aware of his or her imminent death were more likely to regret not having talked about it (47 percent, as compared with 13 percent of parents who did not sense this awareness in their child; relative risk, 3.7; 95 percent confidence interval, 2.3 to 6.0). The same variable was related to having talked about death (50 percent vs. 13 percent; relative risk, 3.8; 95 percent confidence interval, 2.6 to 5.6), as was being religious (42 percent vs. 25 percent; relative risk, 1.7; 95 percent confidence interval, 1.2 to 2.3). The child's age was related to both having talked about death and the parents' regretting not having talked about it.Parents who sense that their child is aware of his or her imminent death more often later regret not having talked with their child than do parents who do not sense this awareness in their child; overall, no parent in this cohort later regretted having talked with his or her child about death.

Receiving a diagnosis of cancer is a traumatic experience that may trigger immediate adverse health consequences beyond the effects of the disease or treatment.Using Poisson and negative binomial regression models, we conducted a historical cohort study involving 6,073,240 Swedes to examine the associations between a cancer diagnosis and the immediate risk of suicide or death from cardiovascular causes from 1991 through 2006. To adjust for unmeasured confounders, we also performed a nested, self-matched case-crossover analysis among all patients with cancer who died from suicide or cardiovascular diseases in the cohort.As compared with cancer-free persons, the relative risk of suicide among patients receiving a cancer diagnosis was 12.6 (95% confidence interval [CI], 8.6 to 17.8) during the first week (29 patients; incidence rate, 2.50 per 1000 person-years) and 3.1 (95% CI, 2.7 to 3.5) during the first year (260 patients; incidence rate, 0.60 per 1000 person-years). The relative risk of cardiovascular death after diagnosis was 5.6 (95% CI, 5.2 to 5.9) during the first week (1318 patients; incidence rate, 116.80 per 1000 person-years) and 3.3 (95% CI, 3.1 to 3.4) during the first 4 weeks (2641 patients; incidence rate, 65.81 per 1000 person-years). The risk elevations decreased rapidly during the first year after diagnosis. Increased risk was particularly prominent for cancers with a poor prognosis. The case-crossover analysis largely confirmed results from the main analysis.In this large cohort study, patients who had recently received a cancer diagnosis had increased risks of both suicide and death from cardiovascular causes, as compared with cancer-free persons. (Funded by the Swedish Council for Working Life and Social Research and others.).

To assess whether maternal use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of persistent pulmonary hypertension in the newborn, and whether such an effect might differ between specific SSRIs.Population based cohort study using data from the national health registers.Denmark, Finland, Iceland, Norway, and Sweden, 1996-2007.More than 1.6 million infants born after gestational week 33.Risks of persistent pulmonary hypertension of the newborn associated with early and late exposure to SSRIs during pregnancy and adjusted for important maternal and pregnancy characteristics. Comparisons were made between infants exposed and not exposed to SSRIs.Around 30 000 women had used SSRIs during pregnancy and 11 014 had been dispensed an SSRI later than gestational week 20. Exposure to SSRIs in late pregnancy was associated with an increased risk of persistent pulmonary hypertension in the newborn: 33 of 11 014 exposed infants (absolute risk 3 per 1000 liveborn infants compared with the background incidence of 1.2 per 1000); adjusted odds ratio 2.1 (95% confidence interval 1.5 to 3.0). The increased risks of persistent pulmonary hypertension in the newborn for each of the specific SSRIs (sertraline, citalopram, paroxetine, and fluoxetine) were of similar magnitude. Filling a prescription with SSRIs before gestational week 8 yielded slightly increased risks: adjusted odds ratio 1.4 (95% confidence interval 1.0 to 2.0).The risk of persistent pulmonary hypertension of the newborn is low, but use of SSRIs in late pregnancy increases that risk more than twofold. The increased risk seems to be a class effect.

<h3>Importance</h3> Psychiatric reactions to life stressors are common in the general population and may result in immune dysfunction. Whether such reactions contribute to the risk of autoimmune disease remains unclear. <h3>Objective</h3> To determine whether there is an association between stress-related disorders and subsequent autoimmune disease. <h3>Design, Setting, and Participants</h3> Population- and sibling-matched retrospective cohort study conducted in Sweden from January 1, 1981, to December 31, 2013. The cohort included 106 464 exposed patients with stress-related disorders, with 1 064 640 matched unexposed persons and 126 652 full siblings of these patients. <h3>Exposures</h3> Diagnosis of stress-related disorders, ie, posttraumatic stress disorder, acute stress reaction, adjustment disorder, and other stress reactions. <h3>Main Outcomes and Measures</h3> Stress-related disorder and autoimmune diseases were identified through the National Patient Register. The Cox model was used to estimate hazard ratios (HRs) with 95% CIs of 41 autoimmune diseases beyond 1 year after the diagnosis of stress-related disorders, controlling for multiple risk factors. <h3>Results</h3> The median age at diagnosis of stress-related disorders was 41 years (interquartile range, 33-50 years) and 40% of the exposed patients were male. During a mean follow-up of 10 years, the incidence rate of autoimmune diseases was 9.1, 6.0, and 6.5 per 1000 person-years among the exposed, matched unexposed, and sibling cohorts, respectively (absolute rate difference, 3.12 [95% CI, 2.99-3.25] and 2.49 [95% CI, 2.23-2.76] per 1000 person-years compared with the population- and sibling-based reference groups, respectively). Compared with the unexposed population, patients with stress-related disorders were at increased risk of autoimmune disease (HR, 1.36 [95% CI, 1.33-1.40]). The HRs for patients with posttraumatic stress disorder were 1.46 (95% CI, 1.32-1.61) for any and 2.29 (95% CI, 1.72-3.04) for multiple (≥3) autoimmune diseases. These associations were consistent in the sibling-based comparison. Relative risk elevations were more pronounced among younger patients (HR, 1.48 [95% CI, 1.42-1.55]; 1.41 [95% CI, 1.33-1.48]; 1.31 [95% CI, 1.24-1.37]; and 1.23 [95% CI, 1.17-1.30] for age at ≤33, 34-41, 42-50, and ≥51 years, respectively;<i>P</i>for interaction &lt; .001). Persistent use of selective serotonin reuptake inhibitors during the first year of posttraumatic stress disorder diagnosis was associated with attenuated relative risk of autoimmune disease (HR, 3.64 [95% CI, 2.00-6.62]; 2.65 [95% CI, 1.57-4.45]; and 1.82 [95% CI, 1.09-3.02] for duration ≤179, 180-319, and ≥320 days, respectively;<i>P</i>for trend = .03). <h3>Conclusions and Relevance</h3> In this Swedish cohort, exposure to a stress-related disorder was significantly associated with increased risk of subsequent autoimmune disease, compared with matched unexposed individuals and with full siblings. Further studies are needed to better understand the underlying mechanisms.

Abstract: The Nordic countries are Denmark, Finland, Iceland, Norway, and Sweden and comprise a total population of approximately 27 million. The countries provide unique opportunities for joint health registry-based research in large populations with long and complete follow-up, facilitated by shared features, such as the tax-funded and public health care systems, the similar population-based registries, and the personal identity number as unique identifier of all citizens. In this review, we provide an introduction to the health care systems, key registries, and how to navigate the practical and ethical aspects of setting up such studies. For each country, we provide an overview of population statistics and health care expenditures, and describe the operational and administrative organization of the health care system. The Nordic registries provide population-based, routine, and prospective data on individuals lives and health with virtually complete follow-up and exact censoring information. We briefly describe the total population registries, birth registries, patient registries, cancer registries, prescription registries, and causes of death registries with a focus on period of coverage, selected key variables, and potential limitations. Lastly, we discuss some practical and legal perspectives. The potential of joint research is not fully exploited, mainly due to legal and practical difficulties in, for example, cross-border sharing of data. Future tasks include clear and transparent legal pathways and a framework by which practical aspects are facilitated. Keywords: health care system, population characteristics, registries, epidemiology, Scandinavian and Nordic countries

Abstract Background Due to the drastic surge of COVID-19 patients, many countries are considering or already graduating health professional students early to aid professional resources. We aimed to assess outbreak-related psychological distress and symptoms of acute stress reaction (ASR) in health professional students and to characterize individuals with potential need for interventions. Methods We conducted a prospective cohort study of 1442 health professional students at Sichuan University, China. At baseline (October 2019), participants were assessed for childhood adversity, stressful life events, internet addiction, and family functioning. Using multivariable logistic regression, we examined associations of the above exposures with subsequent psychological distress and ASR in response to the outbreak. Results Three hundred and eighty-four (26.63%) participants demonstrated clinically significant psychological distress, while 160 (11.10%) met the criterion for a probable ASR. Individuals who scored high on both childhood adversity and stressful life event experiences during the past year were at increased risks of both distress (ORs 2.00–2.66) and probable ASR (ORs 2.23–3.10), respectively. Moreover, internet addiction was associated with elevated risks of distress (OR 2.05, 95% CI 1.60–2.64) and probable ASR (OR 2.15, 95% CI 1.50–3.10). By contrast, good family functioning was associated with decreased risks of distress (OR 0.43, 95% CI 0.33–0.55) and probable ASR (OR 0.48, 95% CI 0.33–0.69). All associations were independent of baseline psychological distress. Conclusions Our findings suggest that COVID-19 related psychological distress and high symptoms burden of ASR are common among health professional students. Extended family and professional support should be considered for vulnerable individuals during these unprecedented times.

<h3>Importance</h3> Psychiatric comorbidities are common among patients with cancer. However, whether or not there is increased risk of mental disorders during the diagnostic workup leading to a cancer diagnosis was unknown. <h3>Objective</h3> To examine the relative risks of depression, anxiety, substance abuse, somatoform/conversion disorder, and stress reaction/adjustment disorder during the periods before and after cancer diagnosis compared with individuals without cancer. <h3>Design, Setting, and Participants</h3> Nationwide matched cohort study from January 1, 2001, to December 31, 2010, in a Swedish population and health registers. <h3>Main Outcomes and Measures</h3> We estimated the time-varying hazard ratios (HRs) of the first clinical diagnosis of the studied mental disorders from 2 years before cancer diagnosis, through the time of diagnosis, and until 10 years after diagnosis, adjusting for age, sex, calendar period, and educational level. To assess milder mental conditions and symptoms, we further assessed the use of related psychiatric medications for patients with cancer diagnosed during 2008-2009. <h3>Results</h3> The study included 304 118 patients with cancer and 3 041 174 cancer-free individuals who were randomly selected from the Swedish population and individually matched to the patients with cancer on year of birth and sex. The median age at diagnosis for the patients with cancer was 69 years, and 46.9% of the patients were female. The relative rate for all studied mental disorders started to increase from 10 months before cancer diagnosis (HR, 1.1; 95% CI, 1.1-1.2), peaked during the first week after diagnosis (HR, 6.7; 95% CI, 6.1-7.4), and decreased rapidly thereafter but remained elevated 10 years after diagnosis (HR, 1.1; 95% CI, 1.1-1.2). The rate elevation was clear for all main cancers except nonmelanoma skin cancer and was stronger for cancers of poorer prognosis. Compared with cancer-free individuals, increased use of psychiatric medications was noted from 1 month before cancer diagnosis and peaked around 3 months after diagnosis among patients with cancer. <h3>Conclusions and Relevance</h3> Patients diagnosed as having cancer had increased risks of several common mental disorders from the year before diagnosis. These findings support the existing guidelines of integrating psychological management into cancer care and further call for extended vigilance for multiple mental disorders starting from the time of the cancer diagnostic workup.

To assess whether use of specific selective serotonin reuptake inhibitors (SSRIs) or venlafaxine in early pregnancy is associated with an increased risk of birth defects, with emphasis on cardiovascular birth defects even when accounting for lifestyle or other familial confounding.Multicountry population based cohort study, including sibling controlled design.Nordic population (Denmark, Finland, Iceland, Norway, and Sweden) identified from nationwide health registers at different periods in 1996-2010.The full study cohort included women giving birth to 2.3 million live singletons. The sibling cohort included 2288 singleton live births. The sibling controlled analyses included sibling pairs who were discordant for exposure to SSRIs or venlafaxine and birth defects.Prevalence of birth defects, including subtypes of cardiac defects. Odds ratio of birth defects from logistic and conditional logistic regression.Among 36,772 infants exposed to any SSRI in early pregnancy, 3.7% (n=1357) had a birth defect compared with 3.1% of 2,266,875 unexposed infants, yielding a covariate adjusted odds ratio of 1.13 (95% confidence interval 1.06 to 1.20). In the sibling controlled analysis the adjusted odds ratio decreased to 1.06 (0.91 to 1.24). The odds ratios for any cardiac birth defect with use of any SSRI or venlafaxine were 1.15 (95% confidence interval 1.05 to 1.26) in the covariate adjusted analysis and 0.92 (0.72 to 1.17) in the sibling controlled analysis. For atrial and ventricular septal defects the covariate adjusted odds ratio was 1.17 (1.05 to 1.31). Exposure to any SSRI or venlafaxine increased the prevalence of right ventricular outflow tract obstruction defects, with a covariate adjusted odds ratio of 1.48 (1.15 to 1.89). In the sibling controlled analysis the adjusted odds ratio decreased to 0.56 (0.21 to 1.49) for any exposure to SSRIs or venlafaxine and right ventricular outflow tract obstruction defects.In this large Nordic study no substantial increase was found in prevalence of overall cardiac birth defects among infants exposed to SSRIs or venlafaxine in utero. Although the prevalence of septal defects and right ventricular outflow tract defects was higher in exposed infants, the lack of an association in the sibling controlled analyses points against a teratogenic effect of these drugs.

Abstract Objective To assess the association between stress related disorders and subsequent risk of cardiovascular disease. Design Population based, sibling controlled cohort study. Setting Population of Sweden. Participants 136 637 patients in the Swedish National Patient Register with stress related disorders, including post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions, from 1987 to 2013; 171 314 unaffected full siblings of these patients; and 1 366 370 matched unexposed people from the general population. Main outcome measures Primary diagnosis of incident cardiovascular disease—any or specific subtypes (ischaemic heart disease, cerebrovascular disease, emboli/thrombosis, hypertensive diseases, heart failure, arrhythmia/conduction disorder, and fatal cardiovascular disease)—and 16 individual diagnoses of cardiovascular disease. Hazard ratios for cardiovascular disease were derived from Cox models, after controlling for multiple confounders. Results During up to 27 years of follow-up, the crude incidence rate of any cardiovascular disease was 10.5, 8.4, and 6.9 per 1000 person years among exposed patients, their unaffected full siblings, and the matched unexposed individuals, respectively. In sibling based comparisons, the hazard ratio for any cardiovascular disease was 1.64 (95% confidence interval 1.45 to 1.84), with the highest subtype specific hazard ratio observed for heart failure (6.95, 1.88 to 25.68), during the first year after the diagnosis of any stress related disorder. Beyond one year, the hazard ratios became lower (overall 1.29, 1.24 to 1.34), ranging from 1.12 (1.04 to 1.21) for arrhythmia to 2.02 (1.45 to 2.82) for artery thrombosis/embolus. Stress related disorders were more strongly associated with early onset cardiovascular diseases (hazard ratio 1.40 (1.32 to 1.49) for attained age &lt;50) than later onset ones (1.24 (1.18 to 1.30) for attained age ≥50; P for difference=0.002). Except for fatal cardiovascular diseases, these associations were not modified by the presence of psychiatric comorbidity. Analyses within the population matched cohort yielded similar results (hazard ratio 1.71 (1.59 to 1.83) for any cardiovascular disease during the first year of follow-up and 1.36 (1.33 to 1.39) thereafter). Conclusion Stress related disorders are robustly associated with multiple types of cardiovascular disease, independently of familial background, history of somatic/psychiatric diseases, and psychiatric comorbidity.

Long-term mental and physical health consequences of COVID-19 (long COVID) are a persistent public health concern. Little is still known about the long-term mental health of non-hospitalised patients with COVID-19 with varying illness severities. Our aim was to assess the prevalence of adverse mental health symptoms among individuals diagnosed with COVID-19 in the general population by acute infection severity up to 16 months after diagnosis.This observational follow-up study included seven prospectively planned cohorts across six countries (Denmark, Estonia, Iceland, Norway, Sweden, and the UK). Participants were recruited from March 27, 2020, to Aug 13, 2021. Individuals aged 18 years or older were eligible to participate. In a cross-sectional analysis, we contrasted symptom prevalence of depression, anxiety, COVID-19-related distress, and poor sleep quality (screened with validated mental health instruments) among individuals with and without a diagnosis of COVID-19 at entry, 0-16 months from diagnosis. In a cohort analysis, we further used repeated measures to estimate the change in mental health symptoms before and after COVID-19 diagnosis.The analytical cohort consisted of 247 249 individuals, 9979 (4·0%) of whom were diagnosed with COVID-19 during the study period. Mean follow-up was 5·65 months (SD 4·26). Participants diagnosed with COVID-19 presented overall with a higher prevalence of symptoms of depression (prevalence ratio [PR] 1·18 [95% CI 1·03-1·36]) and poorer sleep quality (1·13 [1·03-1·24]) but not symptoms of anxiety (0·97 [0·91-1·03]) or COVID-19-related distress (1·05 [0·93-1·20]) compared with individuals without a COVID-19 diagnosis. Although the prevalence of depression and COVID-19-related distress attenuated with time, individuals diagnosed with COVID-19 but never bedridden due to their illness were consistently at lower risk of depression (PR 0·83 [95% CI 0·75-0·91]) and anxiety (0·77 [0·63-0·94]) than those not diagnosed with COVID-19, whereas patients who were bedridden for more than 7 days were persistently at higher risk of symptoms of depression (PR 1·61 [95% CI 1·27-2·05]) and anxiety (1·43 [1·26-1·63]) than those not diagnosed throughout the study period.Severe acute COVID-19 illness-indicated by extended time bedridden-is associated with long-term mental morbidity among recovering individuals in the general population. These findings call for increased vigilance of adverse mental health development among patients with a severe acute disease phase of COVID-19.Nordforsk, Horizon2020, Wellcome Trust, and Estonian Research Council.

Importance Suicidal ideation is common among women with perinatal depression (PND). However, prospective data are limited on the risk, particularly long-term risk, of suicidal behavior (suicide attempt and completed suicide) among women with perinatal depression. Objective To examine the association between PND and risk of short- and long-term suicidal behavior. Design, Setting, and Participants A nationwide population-matched cohort study was conducted in Sweden including 86 551 women with PND from 2001 to 2017 and 865 510 unaffected women individually matched on age and calendar year at delivery. Sibling comparison was used to account for familial confounding. Data were analyzed from January 2022 to November 2023. Exposure PND was identified through depression diagnosis or filled prescriptions of antidepressants from pregnancy to 1 year post partum in registers. Main Outcomes and Measures All women were followed up for the first event of suicidal behavior recorded in registers. Hazard ratios (HR) of suicidal behavior were estimated using time-to-event analysis. Results Women with PND (86 551 participants) received a diagnosis at a mean (SD) age of 30.67 (5.23) years. During a median (IQR) follow-up of 6.91 (3.62-10.88) years, 3604 events of suicidal behavior (incidence rate [IR], 5.62 per 1000 person-years) were identified among women with PND and 6445 (IR, 1.01 per 1000 person-years) among population-unaffected women. Women with PND had an elevated risk of suicidal behavior when compared with matched unaffected women (HR, 3.15; 95% CI, 2.97-3.35). Comparable, albeit somewhat attenuated, associations were yielded when comparing PND women with their PND-free sisters (HR, 2.75; 95% CI, 2.10-3.61). In the population-matched cohort, the association was greater for postnatal depression and among women without a history of psychiatric disorders. The excess risk was pronounced during the first year after diagnosis (HR, 7.20; 95% CI, 6.07-8.54), yet remained statistically significant during 5 to 18 years of follow-up (HR, 2.34; 95% CI, 2.12-2.57). Conclusions and Relevance In this nationwide cohort study, women with PND were at an increased risk of suicidal behavior, particularly within the first year after diagnosis with persistent risk elevations throughout the 18 years of follow-up, highlighting the need for vigilant clinical monitoring of this vulnerable group.

Abstract Objective To determine whether women with perinatal depression are at an increased risk of death compared with women who did not develop the disorder, and compared with full sisters. Design Nationwide, register based study. Setting Swedish national registers, 1 January 2001 to 31 December 2018. Participants 86 551 women with a first ever diagnosis of perinatal depression ascertained through specialised care and use of antidepressants, and 865 510 women who did not have perinatal depression were identified and matched based on age and calendar year at delivery. To address familial confounding factors, comparisons were made between 270 586 full sisters (women with perinatal depression (n=24 473) and full sisters who did not have this disorder (n=246 113)), who gave at least one singleton birth during the study period. Main outcome measures Primary outcome was death due to any cause. Secondary outcome was cause specific deaths (ie, unnatural and natural causes). Multivariable Cox regression was used to estimate hazard ratios of mortality comparing women with perinatal depression to unaffected women and sisters, taking into account several confounders. The temporal patterns of perinatal depression and differences between antepartum and postpartum onset of perinatal depression were also studied. Results 522 deaths (0.82 per 1000 person years) were reported among women with perinatal depression diagnosed at a median age of 31.0 years (interquartile range 27.0 to 35.0) over up to 18 years of follow-up. Compared with women who did not have perinatal depression, women with perinatal depression were associated with an increased risk of death (adjusted hazard ratio 2.11 (95% confidence interval 1.86 to 2.40)); similar associations were reported among women who had and did not have pre-existing psychiatric disorder. Risk of death seemed to be increased for postpartum than for antepartum depression (hazard ratio 2.71 (95% confidence interval 2.26 to 3.26) v 1.62 (1.34 to 1.94)). A similar association was noted for perinatal depression in the sibling comparison (2.12 (1.16 to 3.88)). The association was most pronounced within the first year after perinatal depression but remained up to 18 years after start of follow up. An increased risk was associated with both unnatural and natural causes of death among women with perinatal depression (4.28 (3.44 to 5.32) v (1.38 (1.16 to 1.64)), with the strongest association noted for suicide (6.34 (4.62 to 8.71)), although suicide was rare (0.23 per 1000 person years). Conclusions Even when accounting for familial factors, women with clinically diagnosed perinatal depression were associated with an increased risk of death, particularly during the first year after diagnosis and because of suicide. Women who are affected, their families, and health professionals should be aware of these severe health hazards after perinatal depression.

Some consider the loss of a child as the most stressful life event. When the death is caused by a malignancy, the parents are commonly exposed not only to their own loss, but also to the protracted physical and emotional suffering of the child. We investigated parental risk of anxiety and depression 4-9 years after the loss of a child owing to a malignancy.In 2001, we attempted to contact all parents in Sweden who had lost a child due to a malignancy during 1992--1997. We used an anonymous postal questionnaire and utilized a control group of non-bereaved parents with a living child.Participation among bereaved parents was 449/561 (80 %); among non-bereaved 457/659 (69%). We found an increased risk of anxiety (relative risk 1.5, 95 % confidence interval 1.1-1.9) and depression (relative risk 1.4, 95 % confidence interval 1.1-1.7) among bereaved parents compared with non-bereaved. The risk of anxiety and depression was higher in the period 4-6 years after bereavement than in the 7-9 years period, during which the average excess risks approached zero. Psychological distress was overall higher among bereaved mothers and loss of a child aged 9 years or older implied an increased risk, particularly for fathers.Psychological morbidity in bereaved parents decreases to levels similar to those among non-bereaved parents 7-9 years after the loss. Bereaved mothers and parents who lose a child 9 years or older have on average an excess risk for long-term psychological distress.

Purpose Palliative care is an important part of cancer treatment. However, little is known about how care-related factors affect bereaved intimates in a long-term perspective. We conducted a population-based, nationwide study addressing this issue, focusing on potential care-related stressors in parents losing a child to cancer. Methods In 2001, we attempted to contact all parents in Sweden who had lost a child to cancer in 1992 to 1997. The parents were asked, through an anonymous postal questionnaire, about their experience of the care given and to what extent these experiences still affect them today. Results Information was supplied by 449 (80%) of 561 eligible parents. Among 196 parents of children whose pain could not be relieved, 111 (57%) were still affected by it 4 to 9 years after bereavement. Among 138 parents reporting that the child had a difficult moment of death, 78 (57%) were still affected by it at follow-up. The probability of parents reporting that their child had a difficult moment of death was increased (relative risk = 1.4; 95% CI, 1.0 to 1.8) if staff were not present at the moment of death. Ten percent of the parents (25 of 251 parents) were not satisfied with the care given during the last month at a pediatric hematology/oncology center; the corresponding figure for care at other hospitals was 20% (33 of 168 parents; P = .0163). Conclusion Physical pain and the moment of death are two important issues to address in end-of-life care of children with cancer in trying to reduce long-term distress in bereaved parents.

Receiving a cancer diagnosis is a stressful event that may increase risks of suicide and cardiovascular death, especially soon after diagnosis. We conducted a cohort study of 342 497 patients diagnosed with prostate cancer from January 1, 1979, through December 31, 2004, in the Surveillance, Epidemiology, and End Results Program. Follow-up started from the date of prostate cancer diagnosis to the end of first 12 calendar months after diagnosis. The relative risks of suicide and cardiovascular death were calculated as standardized mortality ratios (SMRs) comparing corresponding incidences among prostate cancer patients with those of the general US male population, with adjustment for age, calendar period, and state of residence. We compared risks in the first year and months after a prostate cancer diagnosis. The analyses were further stratified by calendar period at diagnosis, tumor characteristics, and other variables. During follow-up, 148 men died of suicide (mortality rate = 0.5 per 1000 person-years) and 6845 died of cardiovascular diseases (mortality rate = 21.8 per 1000 person-years). Patients with prostate cancer were at increased risk of suicide during the first year (SMR = 1.4, 95% confidence interval [CI] = 1.2 to 1.6), especially during the first 3 months (SMR = 1.9, 95% CI = 1.4 to 2.6), after diagnosis. The elevated risk was apparent in pre–prostate-specific antigen (PSA) (1979–1986) and peri–PSA (1987–1992) eras but not since PSA testing has been widespread (1993–2004). The risk of cardiovascular death was slightly elevated during the first year (SMR = 1.09, 95% CI = 1.06 to 1.12), with the highest risk in the first month (SMR = 2.05, 95% CI = 1.89 to 2.22), after diagnosis. The first-month risk was statistically significantly elevated during the entire study period, and the risk was higher for patients with metastatic tumors (SMR = 3.22, 95% CI = 2.68 to 3.84) than for those with local or regional tumors (SMR = 1.57, 95% CI = 1.42 to 1.74). A diagnosis of prostate cancer may increase the immediate risks of suicide and cardiovascular death.

Assessment of cortisol concentrations in hair is one of the latest innovations for measuring long-term cortisol exposure. We performed a systematic review of correlates of cortisol in human hair to inform the design, analysis, and interpretation of future epidemiologic studies. Relevant publications were identified through electronic searches on PubMed, WorldCat, and Web of Science using keywords, “cortisol,” “hair,” “confounders,” “chronic,” “stress,” and “correlates.” Thirty-nine studies were included in this review. Notwithstanding scarce data and some inconsistencies, investigators have found hair cortisol concentrations to be associated with stress-related psychiatric symptoms and disorders (e.g., post-traumatic stress disorder), medical conditions indicating chronic activation of the hypothalamic-pituitary-adrenal axis (e.g., Cushing's syndrome), and other life situations associated with elevated risk of chronic stress (e.g., shiftwork). Results from some studies suggest that physical activity, adiposity, and substance abuse may be correlates of hair cortisol concentrations. In contrast to measures of short-term cortisol release (saliva, blood, and urine), cigarette smoking and use of oral contraceptives appear not to be associated with hair cortisol concentrations. Studies of pregnant women indicate increased hair cortisol concentrations across successive trimesters. The study of hair cortisol presents a unique opportunity to assess chronic alterations in cortisol concentrations in epidemiologic studies.

Abstract Disruption of the circadian system has been hypothesized to increase cancer risk, either because of direct disruption of the molecular machinery generating circadian rhythms or because of disruption of parameters controlled by the clock such as melatonin levels or sleep duration. This hypothesis has been studied in hormone-dependent cancers among women, but data are sparse about potential effects of circadian disruption on the risk of prostate cancer. This review systematically examines available data evaluating the effects of light at night, sleep patterns, and night shift work on prostate cancer risk. Cancer Epidemiol Biomarkers Prev; 21(7); 1002–11. ©2012 AACR.

BACKGROUND: We evaluated whether younger age in class is associated with poorer academic performance and an increased risk of being prescribed stimulants for attention-deficit/hyperactivity disorder (ADHD). METHODS: This was a nationwide population-based cohort study, linking data from national registries of prescribed drugs and standardized scholastic examinations. The study population comprised all children born in 1994–1996 who took standardized tests in Iceland at ages 9 and 12 (n = 11 785). We estimated risks of receiving low test scores (0–10th percentile) and being prescribed stimulants for ADHD. Comparisons were made according to children’s relative age in class. RESULTS: Mean test scores in mathematics and language arts were lowest among the youngest children in the fourth grade, although the gap attenuated in the seventh grade. Compared with the oldest third, those in the youngest third of class had an increased relative risk of receiving a low test score at age 9 for mathematics (1.9; 95% confidence interval [CI] 1.6–2.2) and language arts (1.8; 95% CI 1.6–2.1), whereas at age 12, the relative risk was 1.6 in both subjects. Children in the youngest third of class were 50% more likely (1.5; 95% CI 1.3–1.8) than those in the oldest third to be prescribed stimulants between ages 7 and 14. CONCLUSIONS: Relative age among classmates affects children’s academic performance into puberty, as well as their risk of being prescribed stimulants for ADHD. This should be taken into account when evaluating children’s performance and behavior in school to prevent unnecessary stimulant treatment.

The diagnosis of cancer is strongly associated with the risk of mental disorders even in patients with no previous history of mental disorders. Accumulating data suggest that mental distress may accelerate tumor progression. We hypothesized therefore that mental disorders after a cancer diagnosis may increase the risk of cancer-specific mortality.We conducted a nationwide cohort study including 244 261 cancer patients diagnosed in Sweden during 2004-2009 and followed them through 2010. Through the Swedish Patient Register, we obtained clinical diagnoses of all mental disorders and focused on mood-, anxiety-, and substance abuse disorders (ICD10: F10-F16, F18-F19, F32-F33, F40-F41, and F43-45) that are commonly diagnosed among patients with cancer. We further classified the studied mental disorders into first-onset or recurrent mental disorders. We used Cox regression to estimate multivariable hazard ratios (HRs) with 95% confidence intervals (CIs) as a measure of the association between mental disorders after cancer diagnosis and cancer-specific mortality, adjusting for age, sex, calendar period, educational level, cancer stage, and cancer type at diagnosis.After cancer diagnosis, 11 457 patients were diagnosed with mood-, anxiety-, and substance abuse disorders; of which 7236 were first-onset mental disorders. Patients with a first-onset mental disorder were at increased risk of cancer-specific mortality (HR: 1.82, 95% CI: 1.71-1.92) while patients with a recurrent mental disorder had much lower risk elevation (HR: 1.14, 95% CI: 1.05-1.24). The increased cancer-specific mortality by first-onset mental disorders was observed for almost all cancer sites/groups and the association was stronger for localized cancers (HR: 2.00, 95% CI: 1.73-2.31) than for advanced cancers (HR: 1.49, 95% CI: 1.32-1.69).Patients with a first-onset common mood-, anxiety-, or substance abuse disorder after cancer diagnosis may be at increased risk of cancer-specific death.

Psychiatric morbidities have been associated with a risk of severe infections through compromised immunity, health behaviours, or both. However, data are scarce on the association between multiple types of pre-pandemic psychiatric disorders and COVID-19. We aimed to assess the association between pre-pandemic psychiatric disorders and the subsequent risk of COVID-19 using UK Biobank.For this cohort analysis, we included participants from UK Biobank who were registered in England and excluded individuals who died before Jan 31, 2020, (the start of the COVID-19 outbreak in the UK) or had withdrawn from UK Biobank. Participants diagnosed with a psychiatric disorder before Jan 31 were included in the group of individuals with pre-pandemic psychiatric disorders, whereas participants without a diagnosis before the outbreak were included in the group of individuals without pre-pandemic psychiatric disorders. We used the Public Health England dataset, UK Biobank hospital data, and death registers to collect data on COVID-19 cases. To examine the relationship between pre-pandemic psychiatric disorders and susceptibility to COVID-19, we used logistic regression models to estimate odds ratios (ORs), controlling for multiple confounders and somatic comorbidities. Key outcomes were all COVID-19, COVID-19 specifically diagnosed in inpatient care, and COVID-19-related deaths. ORs were also estimated separately for each psychiatric disorder and on the basis of the number of pre-pandemic psychiatric disorders. As a positive disease control, we repeated analyses for hospitalisation for other infections.We included 421 014 UK Biobank participants in our study and assessed their COVID-19 status between Jan 31 and July 26, 2020. 50 809 participants were diagnosed with psychiatric disorders before the outbreak, while 370 205 participants had no psychiatric disorders. The mean age at outbreak was 67·80 years (SD 8·12). We observed an elevated risk of COVID-19 among individuals with pre-pandemic psychiatric disorders compared with that of individuals without such conditions. The fully adjusted ORs were 1·44 (95% CI 1·28-1·62) for All COVID-19 cases, 1·55 (1·34-1·78) for Inpatient COVID-19 cases, and 2·03 (1·59-2·59) for COVID-19-related deaths. We observed excess risk, defined as risk that increased with the number of pre-pandemic psychiatric disorders, across all diagnostic categories of pre-pandemic psychiatric disorders. We also observed an association between psychiatric disorders and elevated risk of hospitalisation due to other infections (OR 1·74, 95% CI 1·58-1·93).Our findings suggest that pre-existing psychiatric disorders are associated with an increased risk of COVID-19. These findings underscore the need for surveillance of and care for populations with pre-existing psychiatric disorders during the COVID-19 pandemic.National Natural Science Foundation of China.

The purpose was to describe utilization of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), including trends in prevalence, characteristics of users, drug switching and changes in prescribed doses in a large group of pregnant women across four Nordic countries.A drug utilization study based on linked individual-level data from the nationwide prescription- and medical birth registers in Denmark, Iceland, Norway and Sweden. The study population comprised all pregnancies in these countries, resulting in a live birth or stillbirth after gestational week 22 from January 1st 2008 to December 31st 2012 (N = 1 162 470). In addition to the main study drugs SSRIs and SNRIs, we included (concurrent) use of other antidepressants, antipsychotics, anxiolytics and hypnotics.A total of 38 219 (3.3%) pregnancies were exposed to SSRIs and 5 634 (0.5%) to SNRIs. Prevalence of SSRI and SNRI use varied by country (1.8% in Norway to 7.0% in Iceland). Use and prescribed dosages decreased with each passing trimester of pregnancy; prevalence was 2.7% at conception, and 2.1%, 1.7% and 1.3% respectively in 1st, 2nd and 3rd trimester. In 0.6% of pregnancies women filled a prescription before pregnancy and in every trimester. In one third of exposed pregnancies, women were also dispensed anxiolytics, hypnotics or sedatives.Use of SSRI and SNRI use during pregnancy varied between the Nordic countries, but the overall prevalence remained low and relatively stable from 2008 to 2012. The low prevalence of use and high proportion of women who discontinue treatment in pregnancy raise questions about adequate treatment of depression in pregnant women.

Survivors of natural disasters are thought to be at an increased risk of psychiatric disorders, however the extent of this risk, and whether it is linked to pre-existing psychopathology, is not known. We aimed to establish whether Swedish survivors of tsunamis from the 2004 Sumatra-Andaman earthquake had increased risks of psychiatric disorders and suicide attempts 5 years after repatriation.We identified Swedish survivors repatriated from southeast Asia (8762 adults and 3742 children) and 864 088 unexposed adults and 320 828 unexposed children matched for sex, age, and socioeconomic status. We retrieved psychiatric diagnoses and suicide attempts from the Swedish patient register for the 5 years after the tsunami (from Dec 26, 2004, to Jan 31, 2010) and estimated hazard ratios (HRs), then adjusted for pre-tsunami psychiatric disorders, and, for children, for parental pre-tsunami disorders.Exposed adults were more likely than unexposed adults to receive any psychiatric diagnosis (547 [6·2%] vs 47 734 [5·5%]; adjusted HR 1·21, 95% CI 1·11-1·32), particularly stress-related disorders (187 [2·1%] vs 8831 [1·0%]; 2·27, 1·96-2·62) and suicide attempts (38 [0·43%] vs 2752 [0·32%]; 1·54, 1·11-2·13), but not mood or anxiety disorders. Risk of psychiatric diagnoses did not differ between exposed and unexposed children and adolescents (248 [6·6] vs 22 081 [6·9%]; 0·98, 0·86-1·11), although exposed children and adolescents had a higher risk for suicide attempts with uncertain intent (1·43; 1·01-2·02) and stress-related disorders (1·79; 1·30-2·46), mainly during the first 3 months after the tsunami.The 2004 tsunami was, independently of previous psychiatric morbidity, associated with an increased risk of severe psychopathology, mainly stress-related disorders and suicide attempts, in children and adults. Survivors of natural disasters should be targeted with early interventions and active long-term follow-up to prevent, detect, and alleviate psychiatric disorders that might follow.The Swedish Council for Working Life and Social Research, Swedish Board of Health and Welfare, Polish Ministry of Science and Higher Education, Swedish Society for Medical Research.

Melatonin has anticarcinogenic properties in experimental models. We undertook a case–cohort study of 928 Icelandic men without prostate cancer (PCa) nested within the Age, Gene/Environment Susceptibility (AGES)-Reykjavik cohort to investigate the prospective association between first morning-void urinary 6-sulfatoxymelatonin (aMT6s) levels and the subsequent risk for PCa, under the hypothesis that men with lower aMT6s levels have an increased risk for advanced PCa. We used weighted Cox proportional hazards models to assess the association between first morning-void aMT6s levels and PCa risk, adjusting for potential confounders. A total of 111 men were diagnosed with incident PCa, including 24 with advanced disease. Men who reported sleep problems at baseline had lower morning aMT6s levels compared with those who reported no sleep problems. Men with morning aMT6s levels below the median had a fourfold statistically significant increased risk for advanced disease compared with men with levels above the median (hazard ratio: 4.04; 95% confidence interval, 1.26–12.98). These results require replication in larger prospective studies with longer follow-up. In this report, we evaluated the prospective association between urinary aMT6s levels and risk of PCa in an Icelandic population. We found that lower levels of aMT6s were associated with an increased risk for advanced PCa.

To assess whether severe psychiatric reactions to trauma and other adversities are associated with subsequent risk of life threatening infections.Population and sibling matched cohort study.Swedish population.144 919 individuals with stress related disorders (post-traumatic stress disorder (PTSD), acute stress reaction, adjustment disorder, and other stress reactions) identified from 1987 to 2013 compared with 184 612 full siblings of individuals with a diagnosed stress related disorder and 1 449 190 matched individuals without such a diagnosis from the general population.A first inpatient or outpatient visit with a primary diagnosis of severe infections with high mortality rates (ie, sepsis, endocarditis, and meningitis or other central nervous system infections) from the Swedish National Patient Register, and deaths from these infections or infections of any origin from the Cause of Death Register. After controlling for multiple confounders, Cox models were used to estimate hazard ratios of these life threatening infections.The average age at diagnosis of a stress related disorder was 37 years (55 541, 38.3% men). During a mean follow-up of eight years, the incidence of life threatening infections per 1000 person years was 2.9 in individuals with a stress related disorder, 1.7 in siblings without a diagnosis, and 1.3 in matched individuals without a diagnosis. Compared with full siblings without a diagnosis of a stress related disorder, individuals with such a diagnosis were at increased risk of life threatening infections (hazard ratio for any stress related disorder was 1.47 (95% confidence intervals1.37 to 1.58) and for PTSD was 1.92 (1.46 to 2.52)). Corresponding estimates in the population based analysis were similar (1.58 (1.51 to 1.65) for any stress related disorder, P=0.09 for difference between sibling and population based comparison, and 1.95 (1.66 to 2.28) for PTSD, P=0.92 for difference). Stress related disorders were associated with all studied life threatening infections, with the highest relative risk observed for meningitis (sibling based analysis 1.63 (1.23 to 2.16)) and endocarditis (1.57 (1.08 to 2.30)). Younger age at diagnosis of a stress related disorder and the presence of psychiatric comorbidity, especially substance use disorders, were associated with higher hazard ratios, whereas use of selective serotonin reuptake inhibitors in the first year after diagnosis of a stress related disorder was associated with attenuated hazard ratios.In the Swedish population, stress related disorders were associated with a subsequent risk of life threatening infections, after controlling for familial background and physical or psychiatric comorbidities.

<h3>Importance</h3> Posttraumatic stress disorder (PTSD) has been associated with increased risk for dementia. Less is known, however, about other stress-related disorders and their associations with neurodegenerative diseases. <h3>Objective</h3> To examine the association between stress-related disorders and risk for neurodegenerative diseases. <h3>Design, Setting, and Participants</h3> This population-matched and sibling cohort study was conducted in Sweden using data from nationwide health registers, including the Swedish National Patient Register. Individuals who received their first diagnosis of stress-related disorders between January 1, 1987, and December 31, 2008, were identified. Individuals who had a history of neurodegenerative diseases, had conflicting or missing information, had no data on family links, or were aged 40 years or younger at the end of the study were excluded. Individuals with stress-related disorders were compared with the general population in a matched cohort design; they were also compared with their siblings in a sibling cohort. Follow-up commenced from the age of 40 years or 5 years after the diagnosis of stress-related disorders, whichever came later, until the first diagnosis of a neurodegenerative disease, death, emigration, or the end of follow-up (December 31, 2013), whichever occurred first. Data analyses were performed from November 2018 to April 2019. <h3>Exposures</h3> Diagnosis of stress-related disorders (PTSD, acute stress reaction, adjustment disorder, and other stress reactions). <h3>Main Outcomes and Measurements</h3> Neurodegenerative diseases were identified through the National Patient Register and classified as primary or vascular. Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis were evaluated separately. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% CIs after controlling for multiple confounders. <h3>Results</h3> The population-matched cohort included 61 748 exposed individuals and 595 335 matched unexposed individuals. A total of 44 839 exposed individuals and their 78 482 unaffected full siblings were included in the sibling cohort analysis. The median (interquartile range) age at the start of follow-up was 47 (41-56) years, and 24 323 (39.4%) of the exposed individuals were male. The median (interquartile range) follow-up was 4.7 (2.1-9.8) years. Compared with unexposed individuals, individuals with a stress-related disorder were at an increased risk of neurodegenerative diseases (HR, 1.57; 95% CI, 1.43-1.73). The risk increase was greater for vascular neurodegenerative diseases (HR, 1.80; 95% CI, 1.40-2.31) than for primary neurodegenerative diseases (HR, 1.31; 95% CI, 1.15-1.48). A statistically significant association was found for Alzheimer disease (HR, 1.36; 95% CI, 1.12-1.67) but not Parkinson disease (HR, 1.20; 95% CI, 0.98-1.47) or amyotrophic lateral sclerosis (HR, 1.20; 95% CI, 0.74-1.96). Results from the sibling cohort corroborated results from the population-matched cohort. <h3>Conclusions and Relevance</h3> This study showed an association between stress-related disorders and an increased risk of neurodegenerative diseases. The relative strength of this association for vascular neurodegenerative diseases suggests a potential cerebrovascular pathway.

Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are associated, but it is unclear if this is a causal relationship or confounding. We used genetic analyses and sibling comparisons to clarify the direction of this relationship.Linkage disequilibrium score regression and 2-sample Mendelian randomization were used to test for genetic correlation (rg) and bidirectional causal effects using European ancestry genome-wide association studies of ADHD (20,183 cases and 35,191 controls) and 6 PTSD definitions (up to 320,369 individuals). Several additional variables were included in the analysis to verify the independence of the ADHD-PTSD relationship. In a population-based sibling comparison (N = 2,082,118 individuals), Cox regression models were fitted to account for time at risk, a range of sociodemographic factors, and unmeasured familial confounders (via sibling comparisons).ADHD and PTSD had consistent rg (rg range, 0.43-0.52; p < .001). ADHD genetic liability was causally linked with increased risk for PTSD (β = 0.367; 95% CI, 0.186-0.552; p = 7.68 × 10-5). This result was not affected by heterogeneity, horizontal pleiotropy (Mendelian randomization Egger intercept = 4.34 × 10-4, p = .961), or other phenotypes and was consistent across PTSD datasets. However, we found no consistent associations between PTSD genetic liability and ADHD risk. Individuals diagnosed with ADHD were at a higher risk for developing PTSD than their undiagnosed sibling (hazard ratio = 2.37; 95% CI, 1.98-3.53).Our findings add novel evidence supporting the need for early and effective treatment of ADHD, as patients with this diagnosis are at significantly higher risk to develop PTSD later in life.

Although major depression, characterized by a pro-inflammatory profile, genetically overlap with autoimmune disease (AD) and the perinatal period involve immune system adaptations and AD symptom alterations, the bidirectional link between perinatal depression (PND) and AD is largely unexplored. Hence, the objective of this study was to investigate the bidirectional association between PND and AD. Using nationwide Swedish population and health registers, we conducted a nested case-control study and a matched cohort study. From 1,347,901 pregnancies during 2001-2013, we included 55,299 incident PND, their unaffected full sisters, and 10 unaffected matched women per PND case. We identified 41 subtypes of AD diagnoses recorded in the registers and compared PND with unaffected population-matched women and full sisters, using multivariable regressions. Women with an AD had a 30% higher risk of subsequent PND (95% CI 1.2-1.5) and women exposed to PND had a 30% higher risk of a subsequent AD (95% CI 1.3-1.4). Comparable associations were found when comparing exposed women with their unaffected sisters (nested case-control OR: 1.3, 95% CI 1.2-1.5, matched cohort HR: 1.3, 95% CI 1.1-1.6), and when studying antepartum and postpartum depression. The bidirectional association was more pronounced among women without psychiatric comorbidities (nested case-control OR: 1.5, 95% CI 1.4-1.6, matched cohort HR: 1.4, 95% CI 1.4-1.5) and strongest for multiple sclerosis (nested case-control OR: 2.0, 95% CI 1.6-2.3, matched cohort HR: 1.8, 95% CI 1.0-3.1). These findings demonstrate a bidirectional association between AD and PND independent of psychiatric comorbidities, suggesting possibly shared biological mechanisms. If future translational science confirms the underlying mechanisms, healthcare providers need to be aware of the increased risk of PND among women with ADs and vice versa.

To investigate the temporal trend of amyotrophic lateral sclerosis (ALS) incidence in Sweden between January 1, 1991, and December 31, 2005, and to explore incidence variations according to major demographic factors.Population-based study.Academic research.All incident cases of ALS identified through the Swedish Inpatient Register between January 1, 1991, and December 31, 2005.Age-standardized incidence rates were calculated by applying the observed age-specific incidence rates to the age distribution of the Swedish population in 1991. A linear regression model was used to assess the potential trend of the incidence during calendar years. We also followed up the entire population registered in the 1990 Population and Housing Census for incidence of ALS. Relative risk and 95% confidence interval of ALS associated with demographic variables were estimated using Poisson regression models.The age-standardized incidence rates increased from 2.32 per 100,000 person-years in 1991-1993 to 2.98 per 100,000 person-years in 2003-2005, representing an annual increase of approximately 2% during the 15 years (P value for trend, .002). The age-specific incidence rates increased in all age groups except those younger than 50 years. The observed increase remained significant when restricting the analysis to individuals born in Sweden (P value for trend, <.001). Compared with individuals born from April through June, those born from October through December were at 11% increased risk of ALS (95% confidence interval, 1.01-1.23).The incidence of ALS has been increasing during the last 15 years in Sweden. Further studies are warranted to explore the underlying reasons for this observed trend.

Stressful life events have been shown to be associated with altered risk of various health consequences. The aim of the present study was to investigate whether the emotional stress evoked by a prostate cancer diagnosis increases the immediate risks of cardiovascular events and suicide.We conducted a prospective cohort study by following all men in Sweden who were 30 y or older (n = 4,305,358) for a diagnosis of prostate cancer (n = 168,584) and their subsequent occurrence of cardiovascular events and suicide between January 1, 1961 and December 31, 2004. We used Poisson regression models to calculate relative risks (RRs) and 95% confidence intervals (CIs) of cardiovascular events and suicide among men who had prostate cancer diagnosed within 1 y to men without any cancer diagnosis. The risks of cardiovascular events and suicide were elevated during the first year after prostate cancer diagnosis, particularly during the first week. Before 1987, the RR of fatal cardiovascular events was 11.2 (95% CI 10.4-12.1) during the first week and 1.9 (95% CI 1.9-2.0) during the first year after diagnosis. From 1987, the RR for cardiovascular events, nonfatal and fatal combined, was 2.8 (95% CI 2.5-3.2) during the first week and 1.3 (95% CI 1.3-1.3) during the first year after diagnosis. While the RR of cardiovascular events declined, the RR of suicide was stable over the entire study period: 8.4 (95% CI 1.9-22.7) during the first week and 2.6 (95% CI 2.1-3.0) during the first year after diagnosis. Men 54 y or younger at cancer diagnosis demonstrated the highest RRs of both cardiovascular events and suicide. A limitation of the present study is the lack of tumor stage data, which precluded possibilities of investigating the potential impact of the disease severity on the relationship between a recent diagnosis of prostate cancer and the risks of cardiovascular events and suicide. In addition, we cannot exclude residual confounding as a possible explanation.Men newly diagnosed with prostate cancer are at increased risks for cardiovascular events and suicide. Future studies with detailed disease characteristic data are warranted.

Psychotic illness following childbirth is a relatively rare but severe condition with unexplained etiology. The aim of this study was to investigate the impact of maternal background characteristics and obstetric factors on the risk of postpartum psychosis, specifically among mothers with no previous psychiatric hospitalizations.We investigated incidence rates and potential maternal and obstetric risk factors of psychoses after childbirth in a national cohort of women who were first-time mothers from 1983 through 2000 (n = 745,596). Proportional hazard regression models were used to estimate relative risks of psychoses during and after the first 90 d postpartum, among mothers without any previous psychiatric hospitalization and among all mothers. Within 90 d after delivery, 892 women (1.2 per 1,000 births; 4.84 per 1,000 person-years) were hospitalized due to psychoses and 436 of these (0.6 per 1,000 births; 2.38 per 1,000 person-years) had not previously been hospitalized for any psychiatric disorder. During follow-up after the 90 d postpartum period, the corresponding incidence rates per 1,000 person-years were reduced to 0.65 for all women and 0.49 for women not previously hospitalized. During (but not after) the first 90 d postpartum the risk of psychoses among women without any previous psychiatric hospitalization was independently affected by: maternal age (35 y or older versus 19 y or younger; hazard ratio 2.4, 95% confidence interval [CI] 1.2 to 4.7); high birth weight (> or = 4,500 g; hazard ratio 0.3, 95% CI 0.1 to 1.0); and diabetes (hazard ratio 0).The incidence of psychotic illness peaks immediately following a first childbirth, and almost 50% of the cases are women without any previous psychiatric hospitalization. High maternal age increases the risk while diabetes and high birth weight are associated with reduced risk of first-onset psychoses, distinctly during the postpartum period.

Background We aimed to study care-related determinants of when parents gain awareness of their child's impending death to cancer, and whether the duration of this awareness affects the parents' long-term morbidity. Methods Between August 2001 and October 2001, 449 of 561 (80%) parents who had lost a child due to any malignancy in Sweden between Jan 1, 1992, and Dec 31, 1997 (identified on the Swedish Causes of Death Register), answered a 365-item postal questionnaire designed to ascertain when, before the child's actual death, they had become intellectually and emotionally aware of the child's impending death (awareness time). The primary endpoints were intellectual awareness time (defined as time between intellectual realisation that a disease is fatal and the actual time of death) and emotional awareness time (defined as time between emotional realisation that a disease is fatal and the actual time of death). Parents' awareness of less than 24 h was referred to as a short awareness time. Findings 436 parents answered the question about intellectual awareness and 433 parents answered the question about emotional awareness. 112 parents (26%) reported a short intellectual awareness time and 195 parents (45%) reported a short emotional awareness time. The risk of having short intellectual awareness time was increased if parents had absence of information on their child's fatal condition (mothers relative risk [RR] 3·6 [95% CI 2·3–5·5]; fathers 2·9 [1·8–4·5]) and if curative treatment was used towards the end of life (mothers 4·1 [2·6–6·5]; fathers 2·7 [1·7–4·2]). The risk of short emotional awareness time was increased if parents had absence of information indicating the child would die (mothers 1·5 [1·1–2·0]; fathers 1·8 [1·3–2·5]) and absence of talks about death with the other parent (mothers 1·5 [1·1–2·0]; fathers 1·7 [1·2–2·2]). Compared with fathers who had longer emotional awareness time, fathers with short emotional awareness time had an increased risk of depression (adjusted RR 1·8 [1·0–3·3]) and absence from employment due to sick leave or early retirement (RR 8·5 [1·1–67·8]) at follow-up. This difference was not noted for mothers. Interpretation Health-care professionals can influence parents' intellectual and emotional awareness of a child's impending death due to cancer. Short emotional awareness increases the risk of long-term depression in bereaved fathers.

Maternal psychiatric disease is associated with adverse pregnancy outcomes. Use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy has been associated with congenital anomalies, neonatal withdrawal syndrome, and persistent pulmonary hypertension of the newborn. However, the risk of stillbirth and infant mortality when accounting for previous maternal psychiatric disease remains unknown.To study risk of stillbirth and infant mortality associated with use of SSRIs during pregnancy.Population-based cohort study from all Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) at different periods from 1996 through 2007. The study included women with singleton births. We obtained information on maternal use of SSRIs from prescription registries. Maternal characteristics, pregnancy, and neonatal outcomes were obtained from patient and medical birth registries.We used logistic regression to estimate relative risks of stillbirth, neonatal death, and postneonatal death associated with SSRI use during pregnancy taking into account maternal characteristics and previous psychiatric hospitalization.Among 1,633,877 singleton births in the study, 6054 were stillbirths; 3609, neonatal deaths; and 1578, postneonatal deaths. A total of 29,228 (1.79%) of mothers had filled a prescription for an SSRI during pregnancy. Women exposed to an SSRI presented with higher rates of stillbirth (4.62 vs 3.69 per 1000, P = .01) and postneonatal death (1.38 vs 0.96 per 1000, P = .03) than those who did not. The rate of neonatal death was similar between groups (2.54 vs 2.21 per 1000, P = .24). Yet in multivariable models, SSRI use was not associated with stillbirth (adjusted odds ratio [OR], 1.17; 95% CI, 0.96-1.41; P = .12), neonatal death (adjusted OR, 1.23; 95% CI, 0.96-1.57; P = .11), or postneonatal death (adjusted OR, 1.34; 95% CI, 0.97-1.86; P = .08). Estimates were further attenuated when stratified by previous hospitalization for psychiatric disease. The adjusted OR for stillbirth in women with a previous hospitalization for psychiatric disease was 0.92 (95% CI, 0.66-1.28; P = .62) and was 1.07 (95% CI, 0.84-1.36; P = .59) for those who had not been previously hospitalized. The corresponding ORs for neonatal death were 0.89 (95% CI, 0.58-1.39; P = .62) for women who were hospitalized and 1.14 (95% CI, 0.84-1.56; P = .39) for women who were not. For postneonatal death, the ORs were 1.02 (95% CI, 0.61-1.69; P = .95) for women who were hospitalized and 1.10 (95% CI, 0.71-1.72; P = .66) for women who were not.Among women with singleton births in Nordic countries, no significant association was found between use of SSRIs during pregnancy and risk of stillbirth, neonatal mortality, or postneonatal mortality. However, decisions about use of SSRIs during pregnancy must take into account other perinatal outcomes and the risks associated with maternal mental illness.

Although positive associations have consistently been reported between sleep disruption and breast cancer, less is known about its potential role in prostate cancer.Within the prospective AGES-Reykjavik cohort study, we followed 2,102 men recruited in 2002-2006 until the end of 2009. Participants answered questions on sleep disruption. Information on the occurrence of prostate cancer was obtained through record linkages across the Icelandic Cancer Registry. We used Cox regression models with 95% confidence intervals (CI) to estimate HRs of prostate cancer by symptoms of sleep disruption.During follow-up, 135 men (6.4%) were diagnosed with prostate cancer. Compared with men without sleep disruption, those with problems falling and staying asleep were at significantly increased risk of prostate cancer [HR, 1.7 (95% CI, 1.0-2.9) and 2.1 (95% CI, 1.2-3.7)], respectively, with increasing sleep disruption severity. When restricted to advanced prostate cancer (≥ stage T3 or lethal disease), these associations became even stronger [HR 2.1 (95% CI, 0.7-6.2) and 3.2 (95% CI, 1.1-9.7)]. The results did not change after excluding from the analyses men who woke up during the night, indicative of nocturia, suggesting limited risk of reverse association.Our data suggest that certain aspects of sleep disruption may confer an increased risk of prostate cancer and call for additional, larger studies with longer follow-up times.Prostate cancer is one of the leading public health concerns in men; if confirmed in future studies, the association between sleep disruption and prostate cancer risk may open new avenues for prevention.

Abstract Preclinical studies have suggested that β-adrenergic signaling is involved in pancreatic cancer progression. Prompted by such studies, we investigated an association between beta-blocker drug use with improved cancer-specific survival in a large, general population-based cohort of patients with pancreatic ductal adenocarcinoma (PDAC). All patients diagnosed with a first primary PDAC in Sweden between 2006 and 2009 were identified through the Swedish Cancer Register (n = 2,394). We obtained information about use of beta-blockers and other medications through linkage with the national Prescribed Drug Register. Cancer-specific mortality was assessed using the Swedish Cause of Death Register. We used multivariable Cox regression adjusted for sociodemographic factors, tumor characteristics, comorbidity score, and other medications to estimate HRs and 95% confidence intervals (CI) for cancer-specific mortality associated with beta-blocker use during the 90-day period before cancer diagnosis. A total of 2,054 (86%) died, with pancreatic cancer recorded as the underlying cause of death during a maximum of 5-year follow-up (median 5 months). Patients who used beta-blockers (n = 522) had a lower cancer-specific mortality rate than nonusers (adjusted HR, 0.79; 95% CI, 0.70–0.90; P &amp;lt; 0.001). This observed rate reduction was more pronounced among patients with localized disease at diagnosis (n = 517; adjusted HR, 0.60; 95% CI, 0.43–0.83; P = 0.002), especially for users with higher daily doses (HR, 0.54; 95% CI, 0.35–0.83; P = 0.005). No clear rate differences were observed by beta-blocker receptor selectivity. Our results support the concept that beta-blocker drugs may improve the survival of PDAC patients, particularly among those with localized disease. Cancer Res; 77(13); 3700–7. ©2017 AACR.

Data are scarce on the potential change in suicidal behavior among adolescents and young adults after receiving a cancer diagnosis.We conducted a population-based cohort study including 7 860 629 Swedes at the age of ≥15 during 1987-2009. Among the cohort participants, 12 669 received a first diagnosis of primary cancer between the age of 15 and 30. We measured the relative risks (RRs) of suicidal behavior (defined as completed suicides or suicide attempts) after cancer diagnosis. We also carried out a case-crossover study nested within the cohort to adjust for unmeasured confounders.Twenty-two completed suicides (versus 14 expected) and 136 suicide attempts (versus 80 expected) were identified among the cancer patients. The RR of suicidal behavior was 1.6 [95% confidence interval (CI), 1.4-1.9] after a cancer diagnosis, compared with cancer-free individuals. Risk increase was greatest immediately after diagnosis; the RR was 2.5 (95% CI 1.7-3.5) during the first year after diagnosis and was 1.5 (95% CI 1.2-1.8) thereafter. This pattern was similar for completed suicide and suicide attempts. The elevated risks were evident for majority of the main cancer types, except for cancer in thyroid, testis and melanoma. The case-crossover analysis of suicidal behavior during the first year after cancer diagnosis revealed similar results.Adolescents and young adults receiving a cancer diagnosis are at substantially increased risk of suicidal behavior, particularly during the first year after diagnosis. Although the absolute excess risk is modest, these findings emphasize the need to support and carefully monitor this vulnerable population.

There is a scarcity of data on mental health effects of the global economic recession. In this study, we investigated potential change in self-reported levels of psychological stress in the Icelandic population as a result of the major national economic collapse that occurred in 2008. We used a national cohort of 3,755 persons who responded to a survey administered in 2007 and 2009, including demographic questions and a stress measure (the 4-item Perceived Stress Scale). We used repeated-measures analysis of variance and logistic regression models to assess change in mean stress levels and risk of high stress levels (>90th percentile) in 2009 as compared with 2007. Age-adjusted mean stress levels increased between 2007 and 2009 (P = 0.004), though the increase was observed only for women (P = 0.003), not for men (P = 0.34). Similarly, the odds ratios for experiencing high stress levels were increased only among women (odds ratio (OR) = 1.37), especially among women who were unemployed (OR = 3.38), students (OR = 2.01), had middle levels of education (OR = 1.65), or were in the middle income bracket (OR = 1.59). The findings indicate that psychological stress may have increased following the economic collapse in Iceland, particularly among females in economically vulnerable groups.

Purpose To examine whether maternal cancer during pregnancy is associated with increased risks of stillbirth and infant mortality. Methods On the basis of nationwide health registers, we conducted a study of 3,947,215 singleton births in Sweden from 1973 through 2012. Exposure was defined as maternal cancer diagnosed during pregnancy (number of births = 984) or during the year after pregnancy (number of births = 2,723). We calculated incidence rate ratios (IRRs) for stillbirth and infant mortality, comparing exposed births to unexposed births. Small-for-gestational-age (SGA) and preterm births were examined as secondary outcomes. Results Maternal cancer diagnosed during pregnancy was positively associated with stillbirth (IRR, 2.5; 95% CI, 1.2 to 5.0), mainly stillbirths assessed as SGA (IRR, 4.9; 95% CI, 2.2 to 11.0), and with preterm SGA births (relative risk 3.0; 95% CI, 2.1 to 4.4). Positive associations of maternal cancer diagnosed during pregnancy or the year after pregnancy were noted for both neonatal mortality (deaths within 0 to 27 days; IRR, 2.7; 95% CI, 1.3 to 5.6 and IRR, 2.0; 95% CI, 1.2 to 3.2, respectively) and preterm birth (IRR, 5.8; 95% CI, 5.3 to 6.5 and IRR, 1.6; 95% CI, 1.4 to 1.8, respectively). The positive association with preterm birth was due to iatrogenic instead of spontaneous preterm birth. Preterm birth explained 89% of the association of maternal cancer during pregnancy with neonatal mortality. Conclusion Maternal cancer during pregnancy is associated with increased risks of rare but fatal outcomes, including stillbirth and neonatal mortality. This may be due to conditions associated with fetal growth restriction and iatrogenic preterm birth. Careful monitoring of fetal growth and cautious decision making on preterm delivery should therefore be reinforced.

Patients with depression are at increased risk for a range of comorbid diseases, with, however, unclear explanations. In this large community-based cohort study of the UK Biobank, 24,130 patients diagnosed with depression were compared to 120,366 matched individuals without such a diagnosis. Follow-up was conducted from 6 months after the index date until death or the end of 2019, for the occurrence of 470 medical conditions and 16 specific causes of death. The median age at the time of the depression diagnosis was 62.0 years, and most of the patients were female (63.63%). During a median follow-up of 4.94 years, 129 medical conditions were found to be significantly associated with a prior diagnosis of depression, based on adjusted Cox regression models. Using disease trajectory network analysis to visualize the magnitude of disease–disease associations and the temporal order of the associated medical conditions, we identified three main affected disease clusters after depression (i.e., cardiometabolic diseases, chronic inflammatory diseases, and diseases related to tobacco abuse), which were further linked to a wider range of other conditions. In addition, we also identified three depression-mortality trajectories leading to death due to cardiovascular disease, respiratory system disease and malignant neoplasm. In conclusion, an inpatient diagnosis of depression in later life is associated with three distinct network-based clusters of medical conditions, indicating alterations in the cardiometabolic system, chronic status of inflammation, and tobacco abuse as key pathways to a wide range of other conditions downstream. If replicated, these pathways may constitute promising targets for the health promotion among depression patients.

Background: Adverse childhood experiences (ACEs) have consistently been associated with elevated risk of multiple adverse health outcomes, yet their contribution to coping ability and psychiatric resilience in adulthood is unclear. Methods: Cross-sectional data were derived from the ongoing Stress-And-Gene-Analysis cohort, representing 30% of the Icelandic nationwide female population, 18–69 years. Participants in the current study were 26,198 women with data on 13 ACEs measured with the ACE-International Questionnaire. Self-reported coping ability was measured with the Connor-Davidson Resilience Scale and psychiatric resilience was operationalized as absence of psychiatric morbidity. Generalized linear regression assuming normal or Poisson distribution were used to assess the associations of ACEs with coping ability and psychiatric resilience controlling for multiple confounders. Results: Number of ACEs was inversely associated with adult resilience in a dose-dependent manner; every 1SD unit increase in ACE scores was associated with both lower levels of coping ability ( β = −0.14; 95% CI-0.15,–0.13) and lower psychiatric resilience ( β = −0.28; 95% CI-0.29,–0.27) in adulthood. Compared to women with 0 ACEs, women with ≥5 ACEs had 36% lower prevalence of high coping ability (PR = 0.64, 95% CI 0.59,0.70) and 58% lower prevalence of high psychiatric resilience (PR = 0.42; 95% CI 0.39,0.45). Specific ACEs including emotional neglect, bullying, sexual abuse and mental illness of household member were consistently associated with reduced adult resilience. We observed only slightly attenuated associations after controlling for adult socioeconomic factors and social support in adulthood. Conclusions: Cumulative ACE exposure is associated with lower adult resilience among women, independent of adult socioeconomic factors and social support, indicating that adult resilience may be largely determined in childhood. Funding: This work was supported by the European Research Council (Consolidator grant; UAV, grant number 726413), and the Icelandic Center for Research (Grant of excellence; UAV, grant number 163362-051). HBD was supported by a doctoral grant from the University of Iceland Research Fund.

Maternal immune activation during pregnancy is associated with increased risks of several mental disorders in offspring during childhood, but little is known about how maternal autoimmune diseases during pregnancy are associated with mental health in offspring during and after childhood.To investigate the association between maternal autoimmune diseases before childbirth and risk of mental disorders among offspring up to early adulthood.This population-based nationwide cohort study used data from Danish national registers on singletons born in Denmark from 1978 to 2015 with up to 38 years of follow-up. Data analyses were conducted from March 1, 2020, through September 30, 2021.Maternal autoimmune disease diagnosed before or during pregnancy according to the Danish National Patient Register.The main outcome was mental disorders, defined by hospital diagnoses, in offspring. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for mental disorders.Of the 2 254 234 singleton infants included in the study (median age, 16.7 years [IQR, 10.5-21.7 years]; 51.28% male), 2.26% were born to mothers with autoimmune diseases before childbirth. Exposed participants had an increased risk of overall mental disorders compared with their unexposed counterparts (HR, 1.16; 95% CI, 1.13-1.19; incidence, 9.38 vs 7.91 per 1000 person-years). Increased risks of overall mental disorders in offspring were seen in different age groups for type 1 diabetes (1-5 years: HR, 1.35 [95% CI, 1.17-1.57]; 6-18 years: HR, 1.24 [95% CI, 1.15-1.33]; >18 years: HR, 1.19 [95% CI, 1.09-1.30]) and rheumatoid arthritis (1-5 years: HR, 1.42 [95% CI, 1.16-1.74]; 6-18 years: HR, 1.19 [95% CI, 1.05-1.36]; >18 years: HR, 1.28 [95% CI, 1.02-1.60]). Regarding specific mental disorders, increased risk after exposure to any maternal autoimmune disorder was observed for organic disorders (HR, 1.54; 95% CI, 1.21-1.94), schizophrenia (HR, 1.35; 95% CI, 1.21-1.51), obsessive-compulsive disorder (HR, 1.42; 95% CI, 1.24-1.63), mood disorders (HR, 1.12; 95% CI, 1.04-1.21), and a series of neurodevelopmental disorders (eg, childhood autism [HR, 1.21; 95% CI, 1.08-1.36] and attention-deficit/hyperactivity disorder [HR, 1.19; 95% CI, 1.12-1.26]).In this cohort study in Denmark, prenatal exposure to maternal autoimmune diseases was associated with increased risks of overall and type-specific mental disorders in offspring. Maternal type 1 diabetes and rheumatoid arthritis during pregnancy were associated with offspring's mental health up to early adulthood. Individuals prenatally exposed to autoimmune disease may benefit from long-term surveillance for mental disorders.

The ongoing COVID-19 pandemic has had an unprecedented impact on the lives of people globally and is expected to have profound effects on mental health. Here we aim to describe the mental health burden experienced in Sweden using baseline data of the Omtanke2020 Study.We analysed self-reported, cross-sectional baseline data collected over a 12-month period (June 9, 2020-June 8, 2021) from the Omtanke2020 Study including 27,950 adults in Sweden. Participants were volunteers or actively recruited through existing cohorts and, after providing informed consent, responded to online questionnaires on socio-demographics, mental and physical health, as well as COVID-19 infection and impact. Poisson regression was fitted to assess the relative risk of demonstrating high level symptoms of depression, anxiety, and COVID-19 related distress.The proportion of persons with high level of symptoms was 15.6 %, 9.5 % and 24.5 % for depression, anxiety, and COVID-19 specific post-traumatic stress disorder (PTSD), respectively. Overall, 43.4 % of the participants had significant, clinically relevant symptoms for at least one of the three mental health outcomes and 7.3 % had significant symptoms for all three outcomes. We also observed differences in the prevalence of these outcomes across strata of sex, age, recruitment type, COVID-19 status, region, and seasonality.While the proportion of persons with high mental health burden remains higher than the ones reported in pre-pandemic publications, our estimates are lower than previously reported levels of depression, anxiety, and PTSD during the pandemic in Sweden and elsewhere.

Abstract Anxiety/stress-related disorders have been associated with multiple diseases, whereas a comprehensive assessment of the structure and interplay of subsequent associated diseases and their genetic underpinnings is lacking. Here, we first identify 136, out of 454 tested, medical conditions associated with incident anxiety/stress-related disorders attended in specialized care using a population-based cohort from the nationwide Swedish Patient Register, comprising 70,026 patients with anxiety/stress-related disorders and 1:10 birth year- and sex-matched unaffected individuals. By combining findings from the comorbidity network and disease trajectory analyses, we identify five robust disease clusters to be associated with a prior diagnosis of anxiety/stress-related disorders, featured by predominance of psychiatric disorders, eye diseases, ear diseases, cardiovascular diseases, and skin and genitourinary diseases. These five clusters and their featured diseases are largely validated in the UK Biobank. GWAS analyses based on the UK Biobank identify 3, 33, 40, 4, and 16 significantly independent single nucleotide polymorphisms for the link to the five disease clusters, respectively, which are mapped to several distinct risk genes and biological pathways. These findings motivate further mechanistic explorations and aid early risk assessment for cluster-based disease prevention among patients with newly diagnosed anxiety/stress-related disorders in specialized care.

Mental disorders (MDs) are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders (CMDs). Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and complete genealogies of Denmark and Sweden (n=17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six MDs and 14 CMDs. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with CMDs, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with CMDs was mainly or fully driven by environmental factors. These findings provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.

A proposed nationwide postal questionnaire to Swedish parents who had lost a child due to cancer between 1992 and 1997 was denied approval by the local ethics committee. However, a pilot study to assess the harm and benefit of the questionnaire was approved. 95% of parents found the pilot study valuable; thus, we were allowed to proceed with the main study, which consisted of 129 questions about the child's care and death and five about the parents' perceptions of the study. 423 (99%) parents found the investigation valuable, 285 (68%) were positively affected, and 123 (28%) were negatively affected (10 [2%] of whom, very much). Although the numerical data cannot be directly translated to ethical conclusions, they can provide guidance for future ethical decisions.

We investigated the predictors and long-term consequences of awareness time - the length of time a woman is aware of her husband's impending death from cancer.All women (n = 506) living in Sweden under 80 years of age who lost their husband/partner owing to cancer of the prostate in 1996 or of the urinary bladder in 1995 or 1996 were followed with an anonymous postal questionnaire, 2-4 years after their loss.We received completed questionnaires from 379 of the widows. Of these, 55 (15%) reported an awareness time of 24 hours or less, 56 (15%) of 3-6 months and 95 (26%) of one year or more. The associations between the awareness time and morbidity were of a reverted 'J-shape,' with awareness time of 24 hours or less carrying the highest risk and 3-6/6-12 months the lowest. On comparing the awareness time of 24 hours or less with 3-6 months (preformed response category), the relative risks for anxiety were found to be 1.9. (1.0-3.6) (visual digital scale) and 4.5 (1.0-20.0) for intake of tranquillising drugs. Those not informed of their husband's fatal condition or not provided with psychological support by caregivers during their husband's last months of life had an increased risk of a short awareness time.During a man's terminal cancer illness, the wife's awareness time varies considerably and is influenced by information and psychological support from caregivers. A short awareness time may result in an additional and avoidable psychological trauma.

We investigated if a cancer patient's unrelieved symptoms during the last 3 months of life increase the risk of long-term psychological morbidity of the surviving partner. All women (n=506) living in Sweden under 80 years of age, who lost their husband/partner owing to cancer of the prostate in 1996 or of the urinary bladder in 1995 or 1996 were asked to answer an anonymous postal questionnaire, 2–4 years after their loss. The widows' psychological morbidity was associated with the patient's unrelieved mental symptoms. When the patient was perceived to have been very anxious during last three months of life (compared to no observed symptoms) the relative risks for the widows' psychological morbidity were: 2.5 (1.4–4.3) for depression and 3.4 (1.4–8.2) for anxiety. When comparing reports of the patient's pain (much vs no), the relative risks were 0.8 (0.5–1.2) for widowhood depression, and 0.8 (0.4–1.7) for widowhood anxiety. The patients were found to have had adequate access to physical pain control but poor access to psychological symptom control. Efficiency in diagnosing and treating psychological complications of terminally ill cancer patients may not only improve their quality of life but possibly also prevent long-term psychological morbidity of their surviving partners.

Studies on the suicide risk among patients with amyotrophic lateral sclerosis (ALS) in countries without legalized euthanasia or assisted suicide are important additions to data on the wish to die of these patients. We conducted a population-based cohort study in Sweden between 1965 and 2004, which comprised of 6642 patients with incident ALS identified from the Swedish Inpatient Register. We calculated the standardized mortality ratios (SMRs) of suicide among the patients using the suicide rates of the general Swedish population as a reference. In total, 21 patients committed suicide during follow-up, compared to the predicted 3.6 suicides. Thus, we noted an almost 6-fold increased risk for suicide among ALS patients [SMR 5.8, 95% confidence interval (CI) 3.6–8.8]. Patients who committed suicide were, on average, around 7 years younger at the time of their first period of hospitalization than patients who did not commit suicide. The highest relative risk for suicide was observed within the first year after the patient's first period of hospitalization (SMR 11.2, 95% CI 5.8–19.6). After that, the relative risks decreased with time after hospitalization (P-value for trend = 0.006), but remained elevated 3 years later. The relative risks of suicide among ALS patients did not show a clear trend over time in contrast to the decreasing trend of relative risks for suicide among patients with cancer during the same period. Patients with ALS are at excess risk of suicide in Sweden and the relative risk is higher during the earlier stage of the disease.

Objective: The aim of this study was to investigate psychotropic drug use among children in Iceland between 2003 and 2007. Methods: A nationwide population-based drug use study covering the total pediatric population (ages 0–17) in Iceland. Information was obtained from the National Medicines Registry to calculate prevalence of use by year and psychotropic drug group; incidence by year, psychotropic drug group, child's age and sex, and medical specialty of prescriber; the most commonly used psychotropic chemical substances, off-label and unlicensed use and concomitant psychotropic drug use. Results: The overall prevalence of psychotropic drug use was 48.7 per 1000 Icelandic children in 2007. Stimulants and antidepressants increased in prevalence from 2003 to 2007 and were the two most prevalent psychotropic drug groups, respectively, 28.4 and 23.4 per 1000 children in 2007. A statistically significant trend of declining prevalence (p = 0.00013) and incidence (p = 0.0018) of antidepressant use occurred during the study period. Out of 21,986 psychotropic drugs dispensed in 2007, 25.4% were used off-label. Conclusions: With reference to reports from other European countries, the results indicate extensive psychotropic drug use among children in Iceland between 2003 and 2007. Further scrutiny is needed to assess the rationale behind this widespread use.

The authors examined the impact of a widower's preparedness before his wife's death from cancer on his risk of long-term morbidity. In a population-based study, 691 (76%) of 907 Swedish men who lost a wife to breast, ovarian, or colon cancer in 2000 or 2001 answered an anonymous questionnaire in 2004 or 2005 measuring preparedness at the time of the wife's death and psychological well-being at follow-up. Men aged 38-61 years with a low degree of preparedness at the time of their spouse's death had increased risk of psychological morbidity and other symptoms, such as anxiety (adjusted relative risk (aRR) = 2.1, 95% confidence interval (CI): 1.0, 4.3), a heightened startle response (aRR = 5.3, 95% CI: 1.2, 23.6), emotional numbness (aRR = 2.1, 95% CI: 1.2, 3.6), little or no grief resolution (aRR = 2.7, 95% CI: 1.3, 5.4), and sleep disorders (aRR = 2.3, 95% CI: 1.2, 4.3), 4-5 years after the loss. For older widowers (aged 62-80 years), a low degree of preparedness increased the risk of having repeated painful memories (aRR = 2.8, 95% CI: 1.5, 5.2) and a heightened startle response (aRR = 5.7, 95% CI: 1.5, 21.4) at follow-up. These results show that to improve the long-term psychological well-being of widowers, it may be fruitful to identify care-related facilitators and inhibitors of preparedness.

The authors investigated whether early-life residency in certain areas of Iceland marked by distinct differences in milk intake was associated with risk of prostate cancer in a population-based cohort of 8,894 men born between 1907 and 1935. Through linkage to cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality from study entry (in waves from 1967 to 1987) through 2009. In 2002-2006, a subgroup of 2,268 participants reported their milk intake in early, mid-, and current life. During a mean follow-up period of 24.3 years, 1,123 men were diagnosed with prostate cancer, including 371 with advanced disease (stage 3 or higher or prostate cancer death). Compared with early-life residency in the capital area, rural residency in the first 20 years of life was marginally associated with increased risk of advanced prostate cancer (hazard ratio = 1.29, 95% confidence interval (CI): 0.97, 1.73), particularly among men born before 1920 (hazard ratio = 1.64, 95% CI: 1.06, 2.56). Daily milk consumption in adolescence (vs. less than daily), but not in midlife or currently, was associated with a 3.2-fold risk of advanced prostate cancer (95% CI: 1.25, 8.28). These data suggest that frequent milk intake in adolescence increases risk of advanced prostate cancer.

Objectives: Chronic pain is a debilitating condition that may cause additional symptoms affecting the sufferers’ working capacity and quality of life. Studying the prevalence and consequences of chronic pain in various populations remains important for a complete picture of the global burden imposed by chronic pain conditions.Methods: We investigated the prevalence of self-reported chronic pain conditions in Iceland in addition to symptoms and functional limitations within the group, using a population-based random sample. A questionnaire was mailed to 9807 Icelanders aged 18–79 years and, of these, 5906 participated in the study. Chronic pain was considered manifest in people reporting chronic low back pain, chronic neck symptoms, and/or fibromyalgia. Prevalence calculations were weighted with respect to gender, age, and residential area to represent the underlying population. Associations of chronic pain conditions with symptoms and functional limitations were measured with adjusted logistic regression models, contrasting symptoms in individuals reporting any of the three pain conditions with those who did not.Results: The population-estimated prevalence of chronic pain condition was 19.9% with distinct gender differences (men = 15.2%, women = 24.7%). Several symptoms and functional limitations in daily life were strongly associated with chronic pain, including deficient energy and muscular discomfort, physical mobility limitations, lifting groceries, climbing stairs, and stooping. Women, but not men, with chronic pain tended to refrain from physical activity.Conclusions: Chronic pain is a prevalent condition and those who report chronic pain generally suffer from ill health and limitations in their daily life compared to individuals not suffering from the condition.

The study aimed to determine whether exposure to a volcanic eruption was associated with increased prevalence of physical and/or mental symptoms.Cohort, with non-exposed control group.Natural disasters like volcanic eruptions constitute a major public-health threat. The Icelandic volcano Eyjafjallajökull exposed residents in southern Iceland to continuous ash fall for more than 5 weeks in spring 2010. This study was conducted during November 2010-March 2011, 6-9 months after the Eyjafjallajökull eruption.Adult (18-80 years of age) eruption-exposed South Icelanders (N=1148) and a control population of residents of Skagafjörður, North Iceland (N=510). The participation rate was 72%.Physical symptoms in the previous year (chronic), in the previous month (recent), General Health Questionnaire (GHQ-12) measured psychological morbidity.The likelihood of having symptoms during the last month was higher in the exposed population, such as; tightness in the chest (OR 2.5; 95% CI 1.1 to 5.8), cough (OR 2.6; 95% CI 1.7 to 3.9), phlegm (OR 2.1; 95% CI 1.3 to 3.2), eye irritation (OR 2.9; 95% CI 2.0 to 4.1) and psychological morbidity symptoms (OR 1.3; 95% CI 1.0 to 1.7). Respiratory symptoms during the last 12 months were also more common in the exposed population; cough (OR 2.2; 95% CI 1.6 to 2.9), dyspnoea (OR 1.6; 95% CI 1.1 to 2.3), although the prevalence of underlying asthma and heart disease was similar. Twice as many in the exposed population had two or more symptoms from nose, eyes or upper-respiratory tract (24% vs 13%, p<0.001); these individuals were also more likely to experience psychological morbidity (OR 4.7; 95% CI 3.4 to 6.5) compared with individuals with no symptoms. Most symptoms exhibited a dose-response pattern within the exposed population, corresponding to low, medium and high exposure to the eruption.6-9 months after the Eyjafjallajökull eruption, residents living in the exposed area, particularly those closest to the volcano, had markedly increased prevalence of various physical symptoms. A portion of the exposed population reported multiple symptoms and may be at risk for long-term physical and psychological morbidity. Studies of long-term consequences are therefore warranted.

To investigate the risk of self-injury in parentally cancer-bereaved youth compared with their nonbereaved peers.Population-based study of cancer-bereaved youth and a random sample of matched population controls.Sweden in 2009 and 2010.A total of 952 youth (74.8%) confirmed to be eligible for the study returned the questionnaire: 622 (73.1%) of 851 eligible young adults who lost a parent to cancer between the ages of 13 and 16 years, in 2000 to 2003, and 330 (78.4%) of 451 nonbereaved peers.Cancer bereavement or nonbreavement during the teenage years.Unadjusted and adjusted odds ratios (ORs) of self-injury after January 1, 2000.Among cancer-bereaved youth, 120 (19.5%) reported self-injury compared with 35 (10.6%) of their nonbereaved peers, yielding an OR of 2.0 (95% CI, 1.4-3.0). After controlling for potential confounding factors in childhood (eg, having engaged in self-destructive behavior, having been bullied, having been sexually or physically abused, having no one to share joys and sorrows with, and sex), the adjusted OR was 2.3 (95% CI, 1.4-3.7). The OR for suicide attempts was 1.6 (95% CI, 0.8-3.0).One-fifth of cancer-bereaved youth reported self-injury, representing twice the odds for self-injury in their nonbereaved peers, regardless of any of the adjustments we made. Raised awareness on a broad basis in health care and allied disciplines would enable identification and support provision to this vulnerable group.

We investigated the feasibility of obtaining hair samples from men and women at community-based barbershops and hair salons for analysis of cortisol and assessed sociodemographic and lifestyle correlates of hair cortisol concentrations (HCCs). A total of 102 participants completed the study. Research staff interviewed participants using a structured questionnaire, and samples of hair were collected. HCCs were determined using liquid chromatography-tandem mass spectrometry. Age- and sex-adjusted linear regression models were used to evaluate the association of HCC with covariates. Analyses by race/ethnicity showed highest median HCC in blacks (12.5 [6.9–29.3]) pg/mg) followed by Hispanics (10.7 [5.8–14.9] pg/mg), whites (5.0 [3.8–10.8] pg/mg), and other participants (4.2 [3.3–15.7] pg/mg), P < .01. Current smokers had significantly higher median HCC (11.7 [8.8–18.9] pg/mg) compared with former smokers (4.6 [3.5–14.6] pg/mg) and those who had never smoked (6.9 [4.7–12.8] pg/mg), P = .04. After adjustment for age and sex, geometric mean HCC was 0.72 pg/mg lower in dyed hair compared with hair that was not dyed (β = −0.72, standard error = 0.30, 95% confidence interval, −1.29 to −0.15, P = .02). HCC can be assessed in community-based studies. Future HCC studies should consider cosmetic hair treatment, cigarette smoking, and the potential role of psychosocial stressors in the association between race/ethnicity and HCC.

The aim of this study was to investigate the associations between loss of a life partner and the development of dementia and decline in cognitive function in later life. We used an Icelandic cohort of 4,370 participants in the Age, Gene/Environment Susceptibility-Reykjavik Study who were living as married in 1978 (born in 1907-1935) and were either still married (unexposed cohort) or widowed (exposed cohort) at follow-up (in 2002-2006). We ascertained history of marital status and spouse's death by record linkage to the Registry of the Total Population, Statistics Iceland. The outcome measures were as follows: 1) dementia and mild cognitive impairment; and 2) memory, speed of processing, and executive function. During the observation period, 3,007 individuals remained married and 1,363 lost a spouse through death. We did not find any significant associations between loss of a spouse and our outcome variables, except that widowed women had poorer executive function (mean = -0.08) during the first 2 years after their husbands' deaths compared with still-married women (mean = 0.09). Our findings do not support the notion that the risk of dementia is increased following the loss of a spouse, yet women demonstrate a seemingly temporary decline in executive function following the death of a partner.

Abstract Background: Sleep deficiency is a major public health problem. There are limited human data on whether sleep duration or disruption are risk factors for prostate cancer. Methods: We prospectively followed 32,141 men in the Health Professionals Follow-Up Study who reported their typical sleep duration in 1987, 2000, and 2008. We identified 4,261 incident prostate cancer cases, including 563 lethal cases through 2010. Sleep disruption was assessed in 2004 among 19,639 men, with 930 prostate cancer cases (50 lethal) identified from 2004 to 2010. Cox proportional hazards models were used to evaluate the association between sleep insufficiency and risk of overall and lethal prostate cancer. Results: In 1987, 2% of men reported sleeping ≤5 hours per night. We found no association between habitual sleep duration or change in sleep duration with the risk of advanced or lethal prostate cancer. We also found no association between waking up during the night, difficulty falling asleep, or waking up too early, and risk of prostate cancer. In 2004, 6% of men reported never feeling rested when they woke up; these men had an increased risk of developing lethal prostate cancer compared with those who reported always feeling rested when they woke up (RR, 3.05; 95% CI, 1.15–8.10). Conclusions: We found no consistent association between self-reported sleep duration or sleep disruption and any of our prostate cancer outcomes. Impact: We did not find support for a consistent association between self-reported sleep and risk of advanced or lethal prostate cancer in this large cohort of men. Cancer Epidemiol Biomarkers Prev; 25(2); 302–8. ©2015 AACR.

Background: Traumatic life events have been associated with increased risk of various psychiatric disorders, even suicidality. Our aim was to investigate the association between different traumatic life events and suicidality, by type of event and gender.Methods: Women attending a cancer screening programme in Iceland (n = 689) and a random sample of men from the general population (n = 709) were invited to participate. In a web-based questionnaire, life events were assessed with the Life Stressor Checklist – Revised, and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criterion was used to identify traumatic life events. Reports of lifetime suicidal thoughts, self-harm with suicidal intent and suicide attempt were considered as lifetime suicidality. We used Poisson regression, adjusted for demographic factors, to express relative risks (RRs) as a measure of the associations between traumatic events and suicidality.Results: Response rate was 66% (922/1398). The prevalence of lifetime traumatic events was 76% among women and 77% among men. Lifetime suicidality was 11% among women and 16% among men. An overall association of having experienced traumatic life events with suicidality was observed [RR 2.05, 95% confidence interval (CI) 1.21–3.75], with a stronger association for men (RR 3.14, 95% CI 1.25–7.89) than for women (RR 1.45, 95% CI 0.70–2.99). Increased likelihood for suicidality was observed among those who had experienced interpersonal trauma (RR 2.97, 95% CI 1.67–5.67), childhood trauma (RR 4.09, 95% CI 2.27–7.36) and sexual trauma (RR 3.44, 95% CI 1.85–6.37), with a higher likelihood for men. In addition, an association between non-interpersonal trauma and suicidality was noted among men (RR 3.27, 95% CI 1.30–8.25) but not women (RR 1.27, 95% CI 0.59–2.70).Conclusion: Findings indicate that traumatic life events are associated with suicidality, especially among men, with the strongest association for interpersonal trauma.

Background The World Cancer Research Fund classifies as “strong evidence” the link between obesity and the risk of advanced prostate cancer. In light of the different hormonal profiles associated with where adipose is stored, this study investigated the role of objectively measured body fat distribution and the risk of clinically relevant prostate cancer. Methods This was a prospective study of 1832 men in the Age, Gene/Environment Susceptibility–Reykjavik study. From 2002 to 2006, participants underwent baseline computed tomography imaging of fat deposition, bioelectric impedance analysis, and measurement of body mass index (BMI) and waist circumference. Men were followed through linkage with nationwide cancer registries for the incidence of total (n = 172), high‐grade (Gleason grade ≥8; n = 43), advanced (≥cT3b/N1/M1 at diagnosis or fatal prostate cancer over follow‐up; n = 41), and fatal prostate cancer (n = 31) through 2015. Cox regression was used to evaluate the association between adiposity measures and prostate cancer outcomes. Results Among all men, visceral fat (hazard ratio [HR], 1.31 per 1–standard deviation [SD] increase; 95% confidence interval [CI], 1.00‐1.72) and thigh subcutaneous fat (HR, 1.37 per 1‐SD increase; 95% CI, 1.00‐1.88) were associated with risk of advanced and fatal disease, respectively. Among men who were leaner based on BMI, visceral fat was associated with both advanced and fatal disease. BMI and waist circumference were associated with a higher risk of advanced and fatal disease. No adiposity measures were associated with total or high‐grade disease. Conclusions Specific fat depots as well as BMI and waist circumference were associated with the risk of aggressive prostate cancer, which may help to elucidate underlying mechanisms and target intervention strategies.

Abstract Emerging evidence suggests a role of psychologic factors in the progression of different cancer types. However, it is unclear whether psychologic distress around the time of diagnosis of invasive cervical cancer places patients at a higher risk of cancer-specific mortality, independently of tumor characteristics and treatment modalities. We conducted a nationwide cohort study, including 4,245 patients with newly diagnosed cervical cancer during 2002–2011 in Sweden. Psychologic distress was indicated by a clinical diagnosis of depression, anxiety, or stress reaction and adjustment disorders, or the experience of a stressful life event, including death or severe illness of a family member, divorce, or between jobs, from one year before cancer diagnosis and onwards. We calculated the HRs of cancer-specific mortality among the patients exposed to psychologic distress, compared with unexposed patients, controlling for socioeconomic characteristics and other known prognostic indicators such as tumor and treatment characteristics. We found that patients exposed to psychologic distress had an increased risk of cancer-specific mortality (HR 1.33; 95% CI, 1.14–1.54). The association was primarily driven by distress experienced within one year before or after diagnosis (HR 1.30; 95% CI, 1.11–1.52), but not thereafter (HR 1.12; 95% CI, 0.84–1.49). In summary, our study shows that psychiatric disorders and stressful life events around cancer diagnosis are associated with increased cancer-specific mortality among patients with cervical cancer, independent of tumor characteristics and treatment modality. Significance: These findings support the integration of psychologic screening and intervention in the clinical management of patients with cervical cancer, particularly around the time of cancer diagnosis.

Abstract An association between schizophrenia and subsequent breast cancer has been suggested; however the risk of schizophrenia following a breast cancer is unknown. Moreover, the driving forces of the link are largely unclear. Here, we report the phenotypic and genetic positive associations of schizophrenia with breast cancer and vice versa, based on a Swedish population-based cohort and GWAS data from international consortia. We observe a genetic correlation of 0.14 (95% CI 0.09–0.19) and identify a shared locus at 19p13 ( GATAD2A ) associated with risks of breast cancer and schizophrenia. The epidemiological bidirectional association between breast cancer and schizophrenia may partly be explained by the genetic overlap between the two phenotypes and, hence, shared biological mechanisms.

An increased susceptibility to COVID-19 has been suggested for individuals with neurodegenerative diseases, but data are scarce from longitudinal studies.In this community-based cohort study, we included 96,275 participants of the UK Biobank who had available SARS-CoV-2 test results in Public Health England. Of these, 2617 had a clinical diagnosis of neurodegenerative diseases in the UK Biobank inpatient hospital data before the outbreak of COVID-19 (defined as January 31st, 2020), while the remaining participants constituted the reference group. We then followed both groups from January 31st, 2020 to June 14th, 2021 for ascertainment of COVID-19 outcomes, including any COVID-19, inpatient care for COVID-19, and COVID-19 related death. Logistic regression was applied to estimate the association between neurogenerative disease and risks of COVID-19 outcomes, adjusted for multiple confounders and somatic comorbidities.We observed an elevated risk of COVID-19 outcomes among individuals with a neurodegenerative disease compared with the reference group, corresponding to a fully adjusted odds ratio of 2.47 (95%CI 2.25-2.71) for any COVID-19, 2.18 (95%CI 1.94-2.45) for inpatient COVID-19, and 3.67 (95%CI 3.11-4.34) for COVID-19 related death. Among individuals with a positive test result for SARS-CoV-2, individuals with neurodegenerative diseases had also a higher risk of COVID-19 related death than others (fully adjusted odds ratio 2.08; 95%CI 1.71-2.53).Among UK Biobank participants who received at least one test for SARS-CoV-2, a pre-existing diagnosis of neurodegenerative disease was associated with a subsequently increased risk of COVID-19, especially COVID-19 related death.

WHO aims to eliminate cervical cancer. Whether women with mental illness constitute a group at high-risk and require targeted prevention initiatives remains unknown. We aimed to assess whether women with severe mental illness, psychiatric or neurodevelopmental disorders, have an increased risk of invasive cervical cancer, and an increased risk of precancerous lesions and a lower degree of participation in cervical screening compared with women without severe mental illness.In this population-based observational study, 4 112 598 women from 1973 to 2018 in Sweden were included to compare the risk of invasive cervical cancer, high-grade precancerous cervical lesions (CIN2+), and degree of participation in cervical screening (defined as the proportion of time covered by screening during a period when cervical screening is recommended) between women with and without mental illness. We focused on severe mental illness (ie, diagnosed in specialised psychiatric care) and also investigated milder mental illness (ie, use of psychotropic medications prescribed in primary care without specialist diagnosis) as secondary exposure. In two nested case-control studies, we defined the cases as women who have a diagnosis of invasive cervical cancer or CIN2+, and randomly selected individually matched controls from women who did not have these diagnoses.Women with a specialist diagnosis of mental illness had a higher risk of invasive cervical cancer (hazard ratio 2·39, 95% CI 2·22-2·57) and CIN2+ (2·22, 2·18-2·26) and a 5·0% (4·8-5·2) lower cervical screening participation compared with matched controls. The risk increment of invasive cervical cancer and CIN2+ was greatest for substance misuse, whereas the screening reduction was greatest for intellectual disability and autism. In contrast, women who used prescribed psychotropic medications without specialist diagnosis had slightly higher screening participation and higher risk of CIN2+ but lower risk of invasive cervical cancer than women with neither specialist diagnosis nor medication use.Women with severe mental illness participate less in screening and experience a higher risk of cervical neoplasia. Refined approaches are needed to better target these women in the elimination agenda of cervical cancer.Swedish Cancer Society.

Importance There is emerging evidence that spouses of patients with cancer may have a higher prevalence of mental illness, but these studies have been limited by pre-post designs, focus on a single mental illness, and short follow-up periods. Objectives To assess the overall burden of psychiatric disorders among spouses of patients with cancer vs spouses of individuals without cancer and to describe possible changes in this burden over time. Design, Setting, and Participants This population based cohort study included spouses of patients with cancer (diagnosed 1986-2016 in Denmark and 1973-2014 in Sweden; exposed group) and spouses of individuals without cancer (unexposed group). Members of the unexposed group were individually matched to individuals in the exposed group on the year of birth, sex, and country. Spouses with and without preexisting psychiatric morbidity were analyzed separately. Data analysis was performed between May 2021 and January 2022. Exposures Being spouse to a patient with cancer. Main Outcomes and Measures The main outcome was a clinical diagnosis of psychiatric disorders through hospital-based inpatient or outpatient care. Flexible parametric models and Cox models were fitted to estimate hazard ratios (HRs) with 95% CIs, adjusted for sex, age and year at cohort entry, country, household income, and cancer history. Results Among 546 321 spouses in the exposed group and 2 731 574 in the unexposed group who had no preexisting psychiatry morbidity, 46.0% were male participants, with a median (IQR) age at cohort entry of 60 (51-68) years. During follow-up (median, 8.4 vs 7.6 years), the incidence rate of first-onset psychiatric disorders was 6.8 and 5.9 per 1000 person-years for the exposed and unexposed groups, respectively (37 830 spouses of patients with cancer [6.9%]; 153 607 of spouses of individuals without cancer [5.6%]). Risk of first-onset psychiatric disorders increased by 30% (adjusted HR, 1.30; 95% CI, 1.25-1.34) during the first year after cancer diagnosis, especially for depression (adjusted HR, 1.38; 95% CI, 1.30-1.47) and stress-related disorders (adjusted HR, 2.04; 95% CI, 1.88-2.22). Risk of first-onset psychiatric disorders increased by 14% (adjusted HR, 1.14; 95% CI, 1.13-1.16) during the entire follow-up, which was similar for substance abuse, depression, and stress-related disorders. The risk increase was more prominent among spouses of patients diagnosed with a cancer with poor prognosis (eg, pancreatic cancer: adjusted HR, 1.41; 95% CI, 1.32-1.51) or at an advanced stage (adjusted HR, 1.31; 95% CI, 1.26-1.36) and when the patient died during follow-up (adjusted HR, 1.29; 95% CI, 1.27-1.31). Among spouses with preexisting psychiatric morbidity, the risk of psychiatric disorders (first-onset or recurrent) increased by 23% during the entire follow-up (adjusted HR, 1.23; 95% CI, 1.20-1.25). Conclusions and Relevance In this cohort study of 2 populations in Denmark and Sweden, spouses of patients with cancer experienced increased risk of several psychiatric disorders that required hospital-based specialist care. Our results support the need for clinical awareness to prevent potential mental illness among the spouses of patients with cancer.

<h2>Summary</h2><h3>Background</h3> Several psychiatric disorders have been associated with increased risk of cardiovascular disease (CVD), however, the role of familial factors and the main disease trajectories remain unknown. <h3>Methods</h3> In this longitudinal cohort study, we identified a cohort of 900,240 patients newly diagnosed with psychiatric disorders during January 1, 1987 and December 31, 2016, their 1,002,888 unaffected full siblings, and 1:10 age- and sex-matched reference population from nationwide medical records in Sweden, who had no prior diagnosis of CVD at enrolment. We used flexible parametric models to determine the time-varying association between first-onset psychiatric disorders and incident CVD and CVD death, comparing rates of CVD among patients with psychiatric disorders to the rates of unaffected siblings and matched reference population. We also used disease trajectory analysis to identify main disease trajectories linking psychiatric disorders to CVD. Identified associations and disease trajectories of the Swedish cohort were validated in a similar cohort from nationwide medical records in Denmark (N = 875,634 patients, same criteria during January 1, 1969 and December 31, 2016) and in Estonian cohorts from the Estonian Biobank (N = 30,656 patients, same criteria during January 1, 2006 and December 31, 2020), respectively. <h3>Findings</h3> During up to 30 years of follow-up of the Swedish cohort, the crude incidence rate of CVD was 9.7, 7.4 and 7.0 per 1000 person-years among patients with psychiatric disorders, their unaffected siblings, and the matched reference population. Compared with their siblings, patients with psychiatric disorders experienced higher rates of CVD during the first year after diagnosis (hazard ratio [HR], 1.88; 95% confidence interval [CI], 1.79–1.98) and thereafter (1.37; 95% CI, 1.34–1.39). Similar rate increases were noted when comparing with the matched reference population. These results were replicated in the Danish cohort. We identified several disease trajectories linking psychiatric disorders to CVD in the Swedish cohort, with or without mediating medical conditions, including a direct link between psychiatric disorders and hypertensive disorder, ischemic heart disease, venous thromboembolism, angina pectoris, and stroke. These trajectories were validated in the Estonian Biobank cohort. <h3>Interpretation</h3> Independent of familial factors, patients with psychiatric disorders are at an elevated risk of subsequent CVD, particularly during first year after diagnosis. Increased surveillance and treatment of CVDs and CVD risk factors should be considered as an integral part of clinical management, in order to reduce risk of CVD among patients with psychiatric disorders. <h3>Funding</h3> This research was supported by EU Horizon 2020 Research and Innovation Action Grant, European Research Council Consolidator grant, Icelandic Research fund, Swedish Research Council, US NIMH, the Outstanding Clinical Discipline Project of Shanghai Pudong, the Fundamental Research Funds for the Central Universities, and the European Union through the European Regional Development Fund; the Research Council of Norway; the South-East Regional Health Authority, the Stiftelsen Kristian Gerhard Jebsen, and the EEA-RO-NO-2018-0535.

Background: Parental feelings of guilt can be a serious problem after the death of a child to a malignancy. This study identified predictors of feelings of guilt in parents during the year after a child's death. Methods: The Swedish Cause of Death Register and Swedish Cancer Register were used to identify all parents in Sweden who had a child who died of a malignancy between 1992–1997. Results: Among parents not reporting recent depression, those who were not confident that their child would immediately receive help from the staff in the hospital while he or she was sick with a malignancy (compared to those who felt partly or entirely sure, relative risk [RR] 4.0; 95% confidence interval [CI] 2.1–7.6), were at increased risk for reporting daily or weekly feelings of guilt in the year after the child's death. Parents who perceived that the staff in the pediatric cancer ward were incompetent were at increased risk (compared to parents reporting partial or total competence, RR 3.7; 95% CI 1.6–8.6). Compared to parents reporting that their children had moderate or much access, those who felt their children had little or no access to pain relief, dietary advice, anxiety relief, and relief of other psychological symptoms beside anxiety were at more than two times greater risk for reporting feelings of guilt. Conclusions: Bereaved parents' perceptions of inadequate health care were associated with subsequent feelings of guilt during the year following their child's death due to a malignancy.

To examine the associations between the 2008 economic collapse in Iceland and smoking behaviour at the national and individual levels.A population-based, prospective cohort study based on a mail survey (Health and Wellbeing in Iceland) assessed in 2007 and 2009.National mail survey.Representative cohort (n=3755) of Icelandic adults.Smoking status.A significant reduction in the prevalence of smoking was observed from 2007 (pre-economic collapse) to 2009 (postcollapse) in both males (17.4-14.8%; p 0.01) and females (20.0-17.5%; p 0.01) in the cohort (n=3755). At the individual level of analysis, male former smokers experiencing a reduction in income during the same period were less likely to relapse (OR 0.37; 95% CI 0.16 to 0.85). Female smokers were less likely to quit over time compared to males (OR 0.65; 95% CI 0.45 to 0.93). Among male former smokers who experienced an increase in income between 2007 and 2009, we observed an elevated risk of smoking relapse (OR 4.02; 95% CI 1.15 to 14.00).The national prevalence of smoking in Iceland declined following the 2008 economic crisis. This could be due to the procyclical relationship between macro-economic conditions and smoking behaviour (ie, hard times lead to less smoking because of lower affordability), or it may simply reflect a continuation of trends already in place prior to the crisis. In individual-level analysis, we find that former smokers who experienced a decline in income were less likely to relapse; and conversely, an increase in income raises the risk. However, caution is warranted since these findings are based on small numbers.

Objective We estimated the risk of complications at birth of extremely large babies (≥5000 g). Study Design This was a cohort study including all births of extremely large babies in 1996 through 2005 and comparison cohort with normal birthweight (1:2) identified in the national birth registration. Results There were 343 extremely large babies or 0.9% of all singletons. Compared to the normal birthweight cohort (n = 679), there were increased odds of shoulder dystocia (odds ratio [OR], 26.9; 95% confidence interval [CI], 11.1–65.1), emergency cesarean section (OR, 5.2; 95% CI, 3.4–8.0), and failed labor induction (OR, 4.3; 95% CI, 1.7–11.0). The risk of elective section was not increased (OR, 1.1; 95% CI, 0.6–2.0). Minor congenital malformations were more frequent (OR, 2.1; 95% CI, 1.2–3.7), as were birth injuries (OR, 3.7; 95% CI, 2.1–6.8) and minor metabolic disturbance (OR, 2.5; 95% CI, 1.1–6.2), but not asphyxial births. Conclusion The risk of shoulder dystocia for very large babies is markedly raised, as are minor complications, while for mothers the main risk is emergency section. We estimated the risk of complications at birth of extremely large babies (≥5000 g). This was a cohort study including all births of extremely large babies in 1996 through 2005 and comparison cohort with normal birthweight (1:2) identified in the national birth registration. There were 343 extremely large babies or 0.9% of all singletons. Compared to the normal birthweight cohort (n = 679), there were increased odds of shoulder dystocia (odds ratio [OR], 26.9; 95% confidence interval [CI], 11.1–65.1), emergency cesarean section (OR, 5.2; 95% CI, 3.4–8.0), and failed labor induction (OR, 4.3; 95% CI, 1.7–11.0). The risk of elective section was not increased (OR, 1.1; 95% CI, 0.6–2.0). Minor congenital malformations were more frequent (OR, 2.1; 95% CI, 1.2–3.7), as were birth injuries (OR, 3.7; 95% CI, 2.1–6.8) and minor metabolic disturbance (OR, 2.5; 95% CI, 1.1–6.2), but not asphyxial births. The risk of shoulder dystocia for very large babies is markedly raised, as are minor complications, while for mothers the main risk is emergency section.

Objective Infants born small for gestational age (SGA) or preterm have increased rates of perinatal morbidity and mortality. Stressful events have been suggested as potential contributors to preterm birth (PB) and low birth weight (LBW). We studied the effect of the 2008 economic collapse in Iceland on the risks of adverse birth outcomes. Study design The study population constituted all Icelandic women giving birth to live-born singletons from January 1st 2006 to December 31st 2009. LBW infants were defined as those weighing <2500 grams at birth, PB infants as those born before 37 weeks of gestation and SGA as those with a birth weight for gestational age more than 2 standard deviations (SD's) below the mean according to the Swedish fetal growth curve. We used logistic regression analysis to estimate odds ratios [OR] and corresponding 95 percent confidence intervals [95% CI] of adverse birth outcomes by exposure to calendar time of the economic collapse, i.e. after October 6th 2008. Results Compared to the preceding period, we observed an increased adjusted odds in LBW-deliveries following the collapse (aOR = 1.24, 95% CI [1.02, 1.52]), particularly among infants born to mothers younger than 25 years (aOR = 1.85, 95% CI [1.25, 2.72]) and not working mothers (aOR = 1.61, 95% CI [1.10, 2.35]). Similarly, we found a tendency towards higher incidence of SGA-births (aOR = 1.14, 95% CI [0.86, 1.51]) particularly among children born to mothers younger than 25 years (aOR = 1.87, 95% CI [1.09, 3.23]) and not working mothers (aOR = 1.86, 95% CI [1.09, 3.17]). No change in risk of PB was observed. The increase of LBW was most distinct 6–9 months after the collapse. Conclusion The results suggest an increase in risk of LBW shortly after the collapse of the Icelandic national economy. The increase in LBW seems to be driven by reduced fetal growth rate rather than shorter gestation.

Air pollutants in Iceland's capital area include hydrogen sulfide (H2S) emissions from geothermal power plants, particle pollution (PM10) and traffic-related pollutants. Respiratory health effects of exposure to PM and traffic pollutants are well documented, yet this is one of the first studies to investigate short-term health effects of ambient H2S exposure. The aim of this study was to investigate the associations between daily ambient levels of H2S, PM10, nitrogen dioxide (NO2) and ozone (O3), and the use of drugs for obstructive pulmonary diseases in adults in Iceland's capital area. The study period was 8 March 2006 to 31 December 2009. We used log-linear Poisson generalized additive regression models with cubic splines to estimate relative risks of individually dispensed drugs by air pollution levels. A three-day moving average of the exposure variables gave the best fit to the data. Final models included significant covariates adjusting for climate and influenza epidemics, as well as time-dependent variables. The three-day moving average of H2S and PM10 levels were positively associated with the number of individuals who were dispensed drugs at lag 3–5, corresponding to a 2.0% (95% confidence interval [CI] 0.4, 3.6) and 0.9% (95% CI 0.1, 1.8) per 10 μg/m3 pollutant concentration increase, respectively. Our findings indicated that intermittent increases in levels of particle matter from traffic and natural sources and ambient H2S levels were weakly associated with increased dispensing of drugs for obstructive pulmonary disease in Iceland's capital area. These weak associations could be confounded by unevaluated variables hence further studies are needed.

To examine whether fish and fish oil consumption across the lifespan is associated with a lower risk of prostate cancer.The study was nested among 2268 men aged 67-96 years in the AGES-Reykjavik cohort study. In 2002 to 2006, dietary habits were assessed, for early life, midlife and later life using a validated food frequency questionnaire. Participants were followed for prostate cancer diagnosis and mortality through 2009 via linkage to nationwide cancer- and mortality registers. Adjusting for potential confounders, we used regression models to estimate odds ratios (ORs) and hazard ratios (HRs) for prostate cancer according to fish and fish oil consumption.Among the 2268 men, we ascertained 214 prevalent and 133 incident prostate cancer cases, of which 63 had advanced disease. High fish consumption in early- and midlife was not associated with overall or advanced prostate cancer. High intake of salted or smoked fish was associated with a 2-fold increased risk of advanced prostate cancer both in early life (95% CI: 1.08, 3.62) and in later life (95% CI: 1.04, 5.00). Men consuming fish oil in later life had a lower risk of advanced prostate cancer [HR (95%CI): 0.43 (0.19, 0.95)], no association was found for early life or midlife consumption.Salted or smoked fish may increase risk of advanced prostate cancer, whereas fish oil consumption may be protective against progression of prostate cancer in elderly men. In a setting with very high fish consumption, no association was found between overall fish consumption in early or midlife and prostate cancer risk.

Purpose To assess children's trust in the care provided to a dying parent during the final week of life in relation to end-of-life medical information about disease, treatment, and death. Methods This nationwide population-based survey included 622 (73%) of 851 youths who, 6 to 9 years earlier, at age 13 to 16 years, lost a parent to cancer. We asked about the children's reception of end-of-life professional information and trust in the care provided. We also asked about depression and several potential risk factors of distrust in the care provided. Results A majority (82%) reported moderate/very much trust in the care provided. Compared with children who received end-of-life medical information before their loss, the risk of distrust in the care provided was higher in those who received no information (risk ratio [RR], 2.5; 95% CI, 1.5 to 4.1), in those who only received information afterward (RR, 3.2; 95% CI, 1.7 to 5.9), and in those who did not know or remember if end-of-life medical information was provided (RR, 1.7; 95% CI, 1.1 to 2.5). Those reporting distrust in the care provided had an RR of 2.3 (95% CI, 1.5 to 3.5) for depression. Furthermore, the risk of distrust in the care provided was higher among children reporting poor efforts to cure (RR, 5.1; 95% CI, 3.6 to 7.3), and/or a poor relationship with the surviving parent (RR, 2.9; 95% CI, 2.0 to 4.1). Conclusion Our study suggests that children's trust in the care provided to a dying parent was highest when they received end-of-life medical information before their loss.

Study Objectives:Limited data exist on the association between trauma and sleep across developmental stages, particularly trauma experienced in childhood and sleep in adulthood. We assessed sleep quality across the developmental spectrum among avalanche survivors 16 years after exposure as compared to a matched comparison cohort.

There are some data to suggest that insufficient sleep, including short sleep duration and sleep disruption, may be associated with an increased risk of cancer. We investigated the association between sleep duration and sleep disruption and risk of prostate cancer.Prospective cohort study.Sweden.A total of 14,041 men in the Swedish National March Cohort.None.Habitual sleep duration and sleep disruption were self-reported in 1997. Prostate cancer diagnoses, including lethal (metastases at diagnosis or death from prostate cancer) and advanced (stage T4, N1, or M1 at diagnosis or death from prostate cancer), were determined from linkage to nationwide cancer registries through 2010. We conducted Cox proportional hazards regression adjusted for potential confounding variables. During 13 years of follow-up, we identified 785 cases of incident prostate cancer, including 118 lethal and 127 advanced cases. Four percent of men reported sleeping 5 h or less a night, and 2% reported sleeping 9 h or more per night. We found no association between sleep duration and risk of prostate cancer overall or for advanced/lethal disease. We also did not find an association between prostate cancer and sleep disruption, as defined by difficulty falling asleep, difficulty maintaining sleep, sleep quality, and restorative power of sleep.In this large prospective study from Sweden, we found no association between habitual sleep duration or sleep disruption and risk of prostate cancer.

Circadian genes may be involved in regulating cancer-related pathways, including cell proliferation, DNA damage response, and apoptosis. We aimed to assess the role of genetic variation in core circadian rhythm genes with the risk of fatal prostate cancer and first morning void urinary 6-sulfatoxymelatonin levels.We used unconditional logistic regression to evaluate the association of 96 single-nucleotide polymorphisms (SNPs) across 12 circadian-related genes with fatal prostate cancer in the AGES-Reykjavik cohort (n = 24 cases), the Health Professionals Follow-Up Study (HPFS) (n = 40 cases), and the Physicians' Health Study (PHS) (n = 105 cases). We used linear regression to evaluate the association between SNPs and first morning void urinary 6-sulfatoxymelatonin levels in AGES-Reykjavik. We used a kernel machine test to evaluate whether multimarker SNP sets in the pathway (gene based) were associated with our outcomes.None of the individual SNPs were consistently associated with fatal prostate cancer across the three cohorts. In each cohort, gene-based analyses showed that variation in the CRY1 gene was nominally associated with fatal prostate cancer (p values = 0.01, 0.01, and 0.05 for AGES-Reykjavik, HPFS, and PHS, respectively). In AGES-Reykjavik, SNPs in TIMELESS (four SNPs), NPAS2 (six SNPs), PER3 (two SNPs) and CSNK1E (one SNP) were nominally associated with 6-sulfatoxymelatonin levels.We did not find a strong and consistent association between variation in core circadian clock genes and fatal prostate cancer risk, but observed nominally significant gene-based associations with fatal prostate cancer and 6-sulfatoxymelatonin levels.

Background. We aimed to investigate cancer-bereaved youths’ opinions and experiences of being told about a parent's imminent death from cancer and of barriers to this communication.Material and methods. This nationwide population-based survey included 622/851 (73%) youths (aged 18–26) who at age 13–16, 6–9 years earlier had lost a parent to cancer.Results. In total 595 of 610 (98%) of the participants stated that teenage children should be informed when the parent's death was imminent (i.e. a matter of hours or days, not weeks). 59% stated that they themselves had been told this, 37% by the parents, 7% by parents and healthcare professionals together and 8% by professionals only. Frequent reasons for why the teenager and parents did not talk about imminent death before loss were that one (n = 106) or both (n = 25) of the parents together with the teenage child had pretended that the illness was not that serious, or that none of the parents had been aware that death was imminent (n = 80). Up to a couple of hours before the loss, 43% of participants had not realized that death was imminent.Conclusion. In this population-based study virtually all youth who at ages 13–16 had lost a parent to cancer afterwards stated that teenagers should be told when loss is near, i.e. a matter of hours or days, not weeks. Many stated that they had not been given this information and few were informed by professionals, with implications for future improvements in end-of-life care of patients with teenage children.

Objective To investigate if marital status is associated with risk of cardiovascular disease (CVD) and to explore the potential influence of leucocyte telomere length (LTL), a marker of biological ageing, on such association. Design Population-based prospective cohort study Settings Swedish Twin Registry. Participants Based on the Screening Across the Lifespan Twin Study from the Swedish Twin Registry, we included 10 058 twins born between 1900 and 1958 who underwent an interview between 1998 and 2002 during which information about marital status was collected. Blood samples from these participants were subsequently collected between 2004 and 2008 and used for LTL assessment using quantitative PCR technique. Main outcome measures Incident cases of CVD were identified through the Swedish Patient Register and Causes of Death Register through December 31, 2016. Multivariable linear regression and Cox proportional hazards regression models were used to estimate the regression coefficients (βs) and HRs with 95% CIs respectively. Potential confounders included age, sex, educational attainment and body mass index. Results A total of 2010 participants were diagnosed with CVD during a median follow-up of 9.8 years. LTL was shorter among individuals living singly, including those who were divorced or separated (β:−0.014, 95% CI: −0.035, 0.007), widowed (β:−0.035, 95% CI: −0.061, –0.010), or living alone (β:−0.033, 95% CI: −0.052, –0.014), than individuals who were married or cohabitating. One SD increase of LTL was associated with a lower risk of CVD (HR: 0.79, 95% CI: 0.66, 0.93). Individuals who were divorced or separated, widowed, or living alone had a higher risk of CVD than individuals who were married or cohabitating. The summary HR of CVD was 1.21 (95% CI: 1.08, 1.35) when comparing individuals who were living singly, regardless of reason, with the individuals who were married or cohabitating. LTL appeared to mediate little of the association between marital status and CVD (HR additionally adjusted for LTL: 1.20; 95% CI: 1.08, 1.34). Conclusions Living singly, regardless of reason, was associated with a shorter LTL and a higher risk of CVD. The association between marital status and CVD was however not greatly attributable to telomere shortening.

Abstract Little is known about how health insurance policies, particularly in developing countries, influence breast cancer prognosis. Here, we examined the association between individual health insurance and breast cancer‐specific mortality in China. We included 7436 women diagnosed with invasive breast cancer between 2009 and 2016, at West China Hospital, Sichuan University. The health insurance plan of patient was classified as either urban or rural schemes and was also categorized as reimbursement rate (ie, the covered/total charge) below or above the median. Breast cancer‐specific mortality was the primary outcome. Using Cox proportional hazards models, we calculated hazard ratios (HRs) for cancer‐specific mortality, contrasting rates among patients with a rural insurance scheme or low reimbursement rate to that of those with an urban insurance scheme or high reimbursement rate, respectively. During a median follow‐up of 3.1 years, we identified 326 deaths due to breast cancer. Compared to patients covered by urban insurance schemes, patients covered by rural insurance schemes had a 29% increased cancer‐specific mortality (95% CI 0%‐65%) after adjusting for demographics, tumor characteristics and treatment modes. Reimbursement rate below the median was associated with a 42% increased rate of cancer‐specific mortality (95% CI 11%‐82%). Every 10% increase in the reimbursement rate is associated with a 7% (95% CI 2%‐12%) reduction in cancer‐specific mortality risk, particularly in patients covered by rural insurance schemes (26%, 95% CI 9%‐39%). Our findings suggest that underinsured patients face a higher risk of breast cancer‐specific mortality in developing countries.

The 2014-15 Holuhraun eruption in Iceland was the largest fissure eruption in over 200 years, emitting prodigious amounts of gas and particulate matter into the troposphere. Reykjavík, the capital area of Iceland (250 km from eruption site) was exposed to air pollution events from advection of (i) a relatively young and chemically primitive volcanic plume with a high sulphur dioxide gas (SO2) to sulphate PM (SO42-) ratio, and (ii) an older and chemically mature volcanic plume with a low SO2/SO42- ratio. Whereas the advection and air pollution caused by the primitive plume were successfully forecast and forewarned in public advisories, the mature plume was not. Here, we show that exposure to the mature plume is associated with an increase in register-measured health care utilisation for respiratory disease by 23% (95% CI 19.7-27.4%) and for asthma medication dispensing by 19.3% (95% CI 9.6-29.1%). Absence of public advisories is associated with increases in visits to primary care medical doctors and to the hospital emergency department. We recommend that operational response to volcanic air pollution considers both primitive and mature types of plumes.

Emerging data suggest that more than two-thirds of premenstrual disorders (PMDs), including premenstrual syndrome and premenstrual dysphoric disorder, have symptom onset during the teen years. Adulthood adiposity has been associated with PMDs; however, the association with childhood and adolescent body size is unknown.To examine the association between childhood and adolescent body size and risk of PMDs in young adulthood.This prospective cohort study included 6524 US female participants from the Growing Up Today Study (1996-2013). Data were analyzed from February 26, 2020, to June 23, 2021.Body mass index (BMI) was estimated using self-reported height and weight through adolescence and converted to BMI for age (z score).In 2013, premenstrual symptoms and identified PMDs were assessed with a validated scale based on the Calendar of Premenstrual Experiences. The associations of BMI for age with PMDs and premenstrual symptoms were examined using log-binomial and linear regressions, respectively.Among 6524 participants (mean [SD] age, 26 [3.5] years; 6108 [93.6%] White), 1004 (15.4%) met the criteria for a PMD. Baseline BMI for age reported at a mean (SD) age of 12.7 (1.1) years was associated with increased risk of PMDs (confounding-adjusted relative risk, 1.09 per unit of z score; 95% CI, 1.03-1.15) and higher burden of premenstrual symptoms (β = 0.06; 95% CI, 0.04-0.08). Associations were particularly pronounced for premenstrual dysphoric disorder and for PMDs with symptom onset before 20 years of age and remained in the absence of psychiatric comorbidities, including depression, anxiety, and disordered eating behavior. When analyzing BMI change over time, individuals with high BMI throughout adolescence had a higher burden of premenstrual symptoms (β = 0.17; 95% CI, 0.08-0.27) compared with those with normal BMI throughout adolescence. Individuals with high BMI early followed by a mild decrease later did not report higher premenstrual symptoms (β = 0.06; 95% CI, 0.00-0.12).In this cohort study, childhood body size was associated with PMD risk and premenstrual symptoms in young adulthood. These findings suggest that maintaining a normal body mass in childhood may be considered for lowering the burden of PMDs in adulthood.

Childhood abuse and neglect have been associated with premenstrual disorders (PMDs), including premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). However, the associations of other adverse childhood experiences (ACEs) and the cumulative number of ACEs with PMDs remain to be explored.To evaluate the associations of the cumulative number and types of ACEs with PMDs, we conducted a cross-sectional analysis with a subsample of menstruating women within the Stress-And-Gene-Analysis (SAGA) cohort, assessed for PMDs and ACEs (N=11,973). The cumulative and individual exposure of 13 types of ACEs was evaluated by a modified ACE-International Questionnaire. A modified version of the Premenstrual Symptom Screening Tool was used to identify probable cases of PMDs, further sub-grouped into PMS and PMDD. Prevalence ratios (PRs) of PMDs in relation to varying ACEs were estimated using Poisson regression.At a mean age of 34.0 years (standard deviation (SD) 9.1), 3235 (27%) met the criteria of probable PMDs, including 2501 (21%) for PMS and 734 (6%) for PMDD. The number of ACEs was linearly associated with PMDs (fully-adjusted PR 1.12 per ACE, 95% CI 1.11-1.13). Specifically, the PR for PMDs was 2.46 (95% CI 2.21-2.74) for women with 4 or more ACEs compared with women with no ACEs. A stronger association was observed for probable PMDD compared to PMS (p for difference <0.001). The associations between ACEs and PMDs were stronger among women without PTSD, anxiety, or depression, and without childhood deprivation and were stronger among women a lower level of social support (p for interaction<0.001). All types of ACEs were positively associated with PMDs (PRs ranged from 1.11 to 1.51); the associations of sexual abuse, emotional neglect, family violence, mental illness of a household member, and peer and collective violence were independent of other ACEs.Our findings suggest that childhood adverse experiences are associated with PMDs in a dose-dependent manner. If confirmed by prospective data, our findings support the importance of early intervention for girls exposed to ACEs to minimize risks of PMDs and other morbidities in adulthood.

Prior research provides suggestive evidence on an association between stress-related disorders and mortality. No previous study has however addressed the role of familial confounding on such association. We conducted a nationwide cohort study of 189,757 individuals with a first-onset stress-related disorder between January 1, 1981 and December 31, 2016 in Sweden (i.e., exposed patients), 1,896,352 matched unexposed individuals, and 207,479 unaffected full siblings of the exposed patients. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause and cause-specific mortality. During a mean follow-up of 9.42 years, an elevated risk of all-cause mortality was observed during the entire follow-up among patients with stress-related disorders, compared with either unexposed individuals or their unaffected full siblings. Such excess risk was most pronounced within the first year after diagnosis of stress-related disorders (HR, 3.19 [95% CI, 2.87-3.54] in population-based comparison; HR, 3.21 [95% CI, 2.56-4.02] in sibling-based comparison). The excess risk decreased but remained statistically significant thereafter (HR, 1.64 [95% CI, 1.60-1.67] in population-based comparison; HR, 1.61 [95% CI, 1.54-1.68] in sibling-based comparison). An increased risk was observed for almost all cause-specific mortality, with greater risk increase for deaths from unnatural causes, especially suicide, and potentially avoidable causes. Stress-related disorders were associated with an increased risk of all-cause mortality and multiple cause-specific mortality, and the risk elevation was independent of familial confounding. The excess mortality attributable to unnatural causes and potentially avoidable causes highlights the importance of clinical surveillance of major health hazards among patients with stress-related disorders. EU Horizon 2020 Research and Innovation Action Grant, 1.3.5 Project for Disciplines of Excellence at West China Hospital of Sichuan University, National Natural Science Foundation of China, Icelandic Research Fund (Grant of Excellence), ERC Consolidator Grant, and Swedish Research Council.

Whether a genetic predisposition to psychiatric disorders is associated with coronavirus disease 2019 (COVID-19) is unknown.Our analytic sample consisted of 287,123 white British participants in UK Biobank who were alive on 31 January 2020. We performed a genome-wide association study (GWAS) analysis for each psychiatric disorder (substance misuse, depression, anxiety, psychotic disorder, and stress-related disorders) in a randomly selected half of the study population ("base dataset"). For the other half ("target dataset"), the polygenic risk score (PRS) was calculated as a proxy of individuals' genetic predisposition to a given psychiatric phenotype using discovered genetic variants from the base dataset. Ascertainment of COVID-19 was based on the Public Health England dataset, inpatient hospital data, or death registers in UK Biobank. COVID-19 cases from hospitalization records or death records were considered "severe cases." The association between the PRS for psychiatric disorders and COVID-19 risk was examined using logistic regression. We also repeated PRS analyses based on publicly available GWAS summary statistics.A total of 143,562 participants (including 10,868 COVID-19 cases) were used for PRS analyses. A higher genetic predisposition to psychiatric disorders was associated with an increased risk of any COVID-19 and severe COVID-19. The adjusted odds ratio (OR) for any COVID-19 was 1.07 (95% confidence interval [CI] 1.02-1.13) and 1.06 (95% CI 1.01-1.11) among individuals with a high genetic risk (above the upper tertile of the PRS) for substance misuse and depression, respectively, compared with individuals with a low genetic risk (below the lower tertile). Slightly higher ORs were noted for severe COVID-19, and similar result patterns were obtained in analyses based on publicly available GWAS summary statistics.Our findings suggest a potential role of genetic factors in the observed phenotypic association between psychiatric disorders and COVID-19. Our data underscore the need for increased medical surveillance for this vulnerable population during the COVID-19 pandemic.

The role of COVID-19 vaccination on the mental health of the general population remains poorly understood. This study aims to assess the short-term change in depressive and anxiety symptoms in relation to COVID-19 vaccination among Swedish adults.A prospective study of 7,925 individuals recruited from ongoing cohort studies at the Karolinska Institutet, Stockholm, Sweden, or through social media campaigns, with monthly data collections on self-reported depressive and anxiety symptoms from December 2020 to October 2021 and COVID-19 vaccination from July to October 2021. Prevalence of depressive and anxiety symptoms (defined as a self-reported total score of ≥10 in PHQ-9 and GAD-7, respectively) was calculated one month before, one month after the first dose, and, if applicable, one month after the second dose. For individuals not vaccinated or choosing not to report vaccination status (unvaccinated individuals), we selected three monthly measures of PHQ-9 and GAD-7 with 2-month intervals in-between based on data availability.5,079 (64.1%) individuals received two doses of COVID-19 vaccine, 1,977 (24.9%) received one dose, 305 (3.9%) were not vaccinated, and 564 (7.1%) chose not to report vaccination status. There was a lower prevalence of depressive and anxiety symptoms among vaccinated, compared to unvaccinated individuals, especially after the second dose. Among individuals receiving two doses of vaccine, the prevalence of depressive and anxiety symptoms was lower after both first (aRR = 0.82, 95%CI 0.76-0.88 for depression; aRR = 0.81, 95%CI 0.73-0.89 for anxiety) and second (aRR = 0.79, 95%CI 0.73-0.85 for depression; aRR = 0.73, 95%CI 0.66-0.81 for anxiety) dose, compared to before vaccination. Similar results were observed among individuals receiving only one dose (aRR = 0.76, 95%CI 0.68-0.84 for depression; aRR = 0.82, 95%CI 0.72-0.94 for anxiety), comparing after first dose to before vaccination.We observed a short-term improvement in depressive and anxiety symptoms among adults receiving COVID-19 vaccines in the current pandemic. Our findings provide new evidence to support outreach campaigns targeting hesitant groups.

Importance Maternal infection is common during pregnancy and is an important potential cause of fetal genetic and immunological abnormalities. Maternal infection has been reported to be associated with childhood leukemia in previous case-control or small cohort studies. Objective To evaluate the association of maternal infection during pregnancy with childhood leukemia among offspring in a large study. Design, Setting, and Participants This population-based cohort study used data from 7 Danish national registries (including the Danish Medical Birth Register, the Danish National Patient Registry, the Danish National Cancer Registry, and others) for all live births in Denmark between 1978 and 2015. Swedish registry data for all live births between 1988 and 2014 were used to validate the findings for the Danish cohort. Data were analyzed from December 2019 to December 2021. Exposures Maternal infection during pregnancy categorized by anatomic locations identified from the Danish National Patient Registry. Main Outcomes and Measures The primary outcome was any leukemia; secondary outcomes were acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML). Offspring childhood leukemia was identified in the Danish National Cancer Registry. Associations were first assessed in the whole cohort using Cox proportional hazards regression models, adjusted for potential confounders. A sibling analysis was performed to account for unmeasured familial confounding. Results This study included 2 222 797 children, 51.3% of whom were boys. During the approximately 27 million person-years of follow-up (mean [SD], 12.0 [4.6] years per person), 1307 children were diagnosed with leukemia (ALL, 1050; AML, 165; or other, 92). Children born to mothers with infection during pregnancy had a 35% increased risk of leukemia (adjusted hazard ratio [HR], 1.35 [95% CI, 1.04-1.77]) compared with offspring of mothers without infection. Maternal genital and urinary tract infections were associated with a 142% and 65% increased risk of childhood leukemia, with HRs of 2.42 (95% CI, 1.50-3.92) and 1.65 (95% CI, 1.15-2.36), respectively. No association was observed for respiratory tract, digestive, or other infections. The sibling analysis showed comparable estimates to the whole-cohort analysis. The association patterns for ALL and AML were similar to that for any leukemia. No association was observed for maternal infection and brain tumors, lymphoma, or other childhood cancers. Conclusions and Relevance In this cohort study of approximately 2.2 million children, maternal genitourinary tract infection during pregnancy was associated with childhood leukemia among offspring. If confirmed in future studies, our findings may have implications for understanding the etiology and developing preventive measures for childhood leukemia.

Objective: Emerging evidence supports a bidirectional phenotypic association between stress-related disorders and autoimmune disease. However, the biological underpinnings remain unclear. Here, the authors examined whether and how shared genetics contribute to the observed phenotypic associations. Methods: Based on data from 4,123,631 individuals identified from Swedish nationwide registers, familial coaggregation of stress-related disorders (any disorder or posttraumatic stress disorder [PTSD]) and autoimmune disease were initially estimated in seven cohorts with different degrees of kinship. Polygenic risk score (PRS) analyses were then performed with individual-level genotyping data from 376,871 participants in the UK Biobank study. Finally, genetic correlation analyses and enrichment analyses were performed with genome-wide association study (GWAS) summary statistics. Results: Familial coaggregation analyses revealed decreasing odds of concurrence of stress-related disorders and autoimmune disease with descending kinship or genetic relatedness between pairs of relatives; adjusted odds ratios were 1.51 (95% CI=1.09–2.07), 1.28 (95% CI=0.97–1.68), 1.16 (95% CI=1.14–1.18), and 1.01 (95% CI=0.98–1.03) for monozygotic twins, dizygotic twins, full siblings, and half cousins, respectively. Statistically significant positive associations were observed between PRSs of stress-related disorders and autoimmune disease, as well as between PRSs of autoimmune disease and stress-related disorders. GWAS summary statistics revealed a genetic correlation of 0.26 (95% CI=0.14–0.38) between these two phenotypes and identified 10 common genes and five shared functional modules, including one module related to G-protein–coupled receptor pathways. Similar analyses performed for PTSD and specific autoimmune diseases (e.g., autoimmune thyroid disease) largely recapitulated the results of the main analyses. Conclusions: This study demonstrated familial coaggregation, genetic correlation, and common biological pathways between stress-related disorders and autoimmune disease.

Abstract Background Persistence of physical symptoms after SARS-CoV-2 infection is a major public health concern, although evidence from large observational studies remain scarce. We aimed to assess the prevalence of physical symptoms in relation to acute illness severity up to more than 2-years after diagnosis of COVID-19. Methods This multinational study included 64 880 adult participants from Iceland, Sweden, Denmark, and Norway with self-reported data on COVID-19 and physical symptoms from April 2020 to August 2022. We compared the prevalence of 15 physical symptoms, measured by the Patient Health Questionnaire (PHQ-15), among individuals with or without a confirmed COVID-19 diagnosis, by acute illness severity, and by time since diagnosis. We additionally assessed the change in symptoms in a subset of Swedish adults with repeated measures, before and after COVID-19 diagnosis. Findings During up to 27 months of follow-up, 22 382 participants (34.5%) were diagnosed with COVID-19. Individuals who were diagnosed with COVID-19, compared to those not diagnosed, had an overall 37% higher prevalence of severe physical symptom burden (PHQ-15 score ≥ 15, adjusted prevalence ratio [PR] 1.37 [95% confidence interval [CI] 1.23-1.52]). The prevalence was associated with acute COVID-19 severity: individuals bedridden for seven days or longer presented with the highest prevalence (PR 2.25[1.85-2.74]), while individuals never bedridden presented with similar prevalence as individuals not diagnosed with COVID-19 (PR 0.92 [0.68-1.24]). The prevalence was statistically significantly elevated among individuals diagnosed with COVID-19 for eight of the fifteen measured symptoms: shortness of breath, chest pain, dizziness, heart racing, headaches, low energy/fatigue, trouble sleeping, and back pain. The analysis of repeated measurements rendered similar results as the main analysis. Interpretation These data suggest an elevated prevalence of some, but not all, physical symptoms during up to more than 2 years after diagnosis of COVID-19, particularly among individuals suffering a severe acute illness. Funding This work was mainly supported by grants from NordForsk (COVIDMENT, grant number 105668 and 138929) and Horizon2020 (CoMorMent, 847776). See Acknowledgements for further details on funding. Research in context Evidence before the study As the majority of the global population has contracted COVID-19, persistence of physical symptoms after SARS-CoV-2 infection ( Long COVID or post COVID-19 condition) has become a major public health concern. We searched PubMed for studies assessing physical symptoms after COVID-19, published by March 22, 2023. The search term was (physical symptoms after covid) AND LitCLONGCOVID [Pubmed filter]. We reviewed 82 studies, after excluding those not on humans or not published in English. High prevalence of multiple physical symptoms, mainly fatigue, shortness of breath, headache, muscle and chest pain, has been reported, mostly based on small samples of hospitalized patients confined to three to six months after diagnosis. A comprehensive assessment of long-term prevalence of physical symptoms beyond six months after diagnosis and among non-hospitalized patients is lacking. Added value of this study We included 64 880 participants from the general population of four Nordic countries, of whom 22 382 had been diagnosed with COVID-19 up to 2 years earlier (&lt;1% hospitalized due to COVID-19). Individuals diagnosed with COVID-19 reported a 37% higher prevalence of overall severe physical symptom burden compared to individuals not diagnosed with COVID-19. We found that shortness of breath, chest pain, dizziness, headaches, and low energy/fatigue were particularly increased among individuals with COVID-19 diagnosis. Individuals bedridden for seven days or more during the acute illness phase (9.6% of the patients) showed the greatest and most persistent elevation in prevalence of severe physical symptoms while individuals not bedridden during the acute COVID-19 illness showed no increase in prevalence of physical symptoms compared to those not diagnosed. Implications of the available evidence Our findings provide timely and valuable evidence to demonstrate the constitution of Long COVID and the long-term health consequences after recovery from COVID-19 in the general population. The long-term risk of severe physical symptom burden is distinctly associated with acute illness severity, highlighting the importance of sustained monitoring of physical symptoms among the group of patients who suffered severe acute illness course.

Abstract Major depressive disorder (MDD) and cardiovascular disease (CVD) are often comorbid, resulting in excess morbidity and mortality. Using genomic data, this study elucidates biological mechanisms, key risk factors, and causal pathways underlying their comorbidity. We show that CVDs share a large proportion of their genetic risk factors with MDD. Multivariate genome-wide association analysis of the shared genetic liability between MDD and atherosclerotic CVD (ASCVD) revealed seven novel loci and distinct patterns of tissue and brain cell-type enrichments, suggesting a role for the thalamus. Part of the genetic overlap was explained by shared inflammatory, metabolic, and psychosocial/lifestyle risk factors. Finally, we found support for causal effects of genetic liability to MDD on CVD risk, but not from most CVDs to MDD, and demonstrated that the causal effects were partly explained by metabolic and psychosocial/lifestyle factors. The distinct signature of MDD-ASCVD comorbidity aligns with the idea of an immunometabolic sub-type of MDD more strongly associated with CVD than overall MDD. In summary, we identify plausible biological mechanisms underlying MDD-CVD comorbidity, as well as key modifiable risk factors for prevention of CVD in individuals with MDD.

We investigated the feasibility of using single-item visual-digital scales for measuring anxiety and depression for research purposes within the oncology and palliative care setting. Data were retrieved from five nationwide postal questionnaires comprising 3030 individuals (response rate 76%): cancer patients, widows/parents who had lost their husband/child to cancer and population controls. All questionnaires contained the Center for Epidemiological Studies Depression scale (CES-D) and Spielberger's State-Trait Anxiety Inventory (STAI-T) as well as seven-point Visual-Digital Scales (VDS) assessing anxiety and depression. Each stepwise increased score on the VDS-depression provided a statistically significant increase in the mean score on CES-D (Spearman's r=0.582). The VDS-anxiety correlated with mean scores on STAI-T (Spearman's r=0.493), however, not all stepwise increased scores on the VDS-anxiety gave a statistically significant increase on the STAI-T. Positive- and negative predictive values were 51% and 91% for VDS-depression and 64% and 80% for VDS-anxiety. Missing data for STAI-T were 7% and 9% for CES-D; the corresponding figures were 2% for the VDS-depression and 3% for VDS-anxiety. With low attrition and agreement with psychometric scales, the Visual-Digital Scales are a feasible alternative for research in the oncology setting. However, the high negative predictive value and the low positive predictive value suggest that the visual- digital scales mainly detect the absence of the symptoms.

If we can learn how to increase preparedness before the death of a loved one, we can possibly decrease the next-of-kin's long-term morbidity.In a population-based study, 691 of 907 (76%) men in Sweden who lost a wife to cancer 4-5 years earlier answered an anonymous questionnaire about their preparedness at the time of their wife's death as well as potential predictors for preparedness.A final logistic regression model indicates following predictors for preparedness, among others: the length of the widower's intellectual awareness time before his wife's death [relative risk (RR) 4.1, confidence interval (CI) 2.7-6.1], the widower could take in the information that his wife's disease could not be cured (RR 3.5, CI 2.3-5.2), the couple had arranged their economical affairs (RR 1.5, CI 1.3-1.7), the wife had stayed at a palliative care unit during her last months of life (RR 1.2, CI 1.1-1.4) and health care personnel supported the husband to participate in his wife's care (RR 1.6, CI 1.3-2.1).We identified several care-related factors that may influence the preparedness of men before their wife's death to cancer. These factors can be considered in future intervention studies aiming at influencing preparedness before the death of a loved one.

Abstract Background Self‐injury, a manifestation of severe psychological distress, is increased in cancer‐bereaved youths. Little is known about the potential influence on the risk for self‐injury of factors that could be clinically relevant to and modifiable by the health‐care professionals involved in the care of the dying parent. Methods In a nationwide population‐based anonymous study, 622 (73.1%) youths (aged 18–26) who, 6 to 9 years earlier at ages 13 to 16, had lost a parent to cancer answered study‐specific questions about self‐injury and factors related to the family and parental health care. Results Univariable analyses showed that the risk for self‐injury was increased among cancer‐bereaved youths who reported poor family cohesion the years before (relative risk [RR], 3.4, 95% confidence interval [CI], 2.5–4.6) and after the loss (RR, 3.3, 95% CI, 2.4–4.4), distrust in the health care provided to the dying parent (RR, 1.7, 95% CI, 1.2–2.4), perceiving poor health‐care efforts to cure the parent (RR 1.5, 95% CI, 1.1–2.1) and poor efforts to prevent suffering (RR, 1.6, 95% CI, 1.1–2.4), that at least one of their parents had been depressed or had troubles in life (RR, 1.5, CI, 1.1–2.1) and believing 3 days before the loss that the treatment would probably cure the parent (RR, 1.6, CI, 1.1–2.3). In the total multivariable models, only poor family cohesion before and after the loss remained statistically significantly associated with self‐injury. Conclusion Poor family cohesion before and after the loss of a parent to cancer is associated with an increased risk of self‐injury in teenage children. Copyright © 2014 John Wiley &amp; Sons, Ltd.

Musculoskeletal chronic pain is a costly public health threat. The aim of our study was to investigate mental health indicators, including self-reported symptoms of depression, sleep disruption, stress, well-being, and quality of life (QoL), among men and women with musculoskeletal chronic pain in a general population.This was a cross-sectional study; a postal questionnaire was mailed to a stratified random sample of 9807 eligible Icelanders retrieved from a national registry, of whom 5906 responded (response rate = 60.2%). Chronic pain conditions included reports of current chronic back pain, chronic neck symptoms, and/or fibromyalgia. Gender-stratified associations of chronic pain conditions with mental health indicators were estimated with logistic regression analyses adjusting for age, income, body mass index (BMI), smoking, education, and residence.We observed higher odds of low satisfaction with life [adjusted odds ratio (OR(adj)) women 2.0, 95% confidence interval (CI) 1.5-2.6; OR(adj) men 2.3, 95% CI 1.7-3.1], higher levels of perceived stress (OR(adj) women 1.7, 95% CI 1.3-2.2; OR(adj) men = 1.5, 95% CI 1.1-2.1), depressive symptoms (OR(adj) women 2.4, 95% CI 1.9-3.0; OR(adj) men 2.8, 95% CI 2.1-3.7), and sleep disruption (OR(adj) women 2.8, 95% CI 2.2-3.5; OR(adj) men 2.2, 95% CI 1.5-3.1), and diminished QoL (OR(adj) women 1.6, 95% CI 1.2-2.1; OR(adj) men 1.5, 95% CI 1.0-2.1) among individuals with chronic pain compared with those without the condition.Our data indicate that individuals with musculoskeletal chronic pain have increased risk of poor mental health and diminished QoL. Further studies are needed on treatment and preventative measures of a decline in mental health among individuals with chronic pain.

OBJECTIVE: We evaluated the hypothesis that later start of stimulant treatment of attention-deficit/hyperactivity disorder adversely affects academic progress in mathematics and language arts among 9- to 12-year-old children. METHODS: We linked nationwide data from the Icelandic Medicines Registry and the Database of National Scholastic Examinations. The study population comprised 11 872 children born in 1994–1996 who took standardized tests in both fourth and seventh grade. We estimated the probability of academic decline (drop of ≥5.0 percentile points) according to drug exposure and timing of treatment start between examinations. To limit confounding by indication, we concentrated on children who started treatment either early or later, but at some point between fourth-grade and seventh-grade standardized tests. RESULTS: In contrast with nonmedicated children, children starting stimulant treatment between their fourth- and seventh-grade tests were more likely to decline in test performance. The crude probability of academic decline was 72.9% in mathematics and 42.9% in language arts for children with a treatment start 25 to 36 months after the fourth-grade test. Compared with those starting treatment earlier (≤12 months after tests), the multivariable adjusted risk ratio (RR) for decline was 1.7 (95% confidence interval [CI]: 1.2–2.4) in mathematics and 1.1 (95% CI: 0.7–1.8) in language arts. The adjusted RR of mathematics decline with later treatment was higher among girls (RR, 2.7; 95% CI: 1.2–6.0) than boys (RR, 1.4; 95% CI: 0.9–2.0). CONCLUSIONS: Later start of stimulant drug treatment of attention-deficit/hyperactivity disorder is associated with academic decline in mathematics.

Except for overall survival, whether or not waiting time for treatment could influences other domains of cancer patients' overall well-being is to a large extent unknown. Therefore, we performed this study to determine the effect of waiting time for cancer treatment on the mental health of patients with esophageal or gastric cancer.Based on the Swedish National Quality Register for Esophageal and Gastric Cancers (NREV), we followed 7,080 patients diagnosed 2006-2012 from the time of treatment decision. Waiting time for treatment was defined as the interval between diagnosis and treatment decision, and was classified into quartiles. Mental disorders were identified by either clinical diagnosis through hospital visit or prescription of psychiatric medications. For patients without any mental disorder before treatment, the association between waiting time and subsequent onset of mental disorders was assessed by hazard ratios (HRs) with 95% confidence interval (CI), derived from multivariable-adjusted Cox model. For patients with a preexisting mental disorder, we compared the rate of psychiatric care by different waiting times, allowing for repeated events.Among 4,120 patients without any preexisting mental disorder, lower risk of new onset mental disorders was noted for patients with longer waiting times, i.e. 18-29 days (HR 0.86; 95% CI 0.74-1.00) and 30-60 days (HR 0.79; 95% CI 0.67-0.93) as compared with 9-17 days. Among 2,312 patients with preexisting mental disorders, longer waiting time was associated with more frequent psychiatric hospital care during the first year after treatment (37.5% higher rate per quartile increase in waiting time; p for trend = 0.0002). However, no such association was observed beyond one year nor for the prescription of psychiatric medications.These data suggest that waiting time to treatment for esophageal or gastric cancer may have different mental health consequences for patients depending on their past psychiatric vulnerabilities. Our study sheds further light on the complexity of waiting time management, and calls for a comprehensive strategy that takes into account different domains of patient well-being in addition to the overall survival.

Purpose Although childhood traumatic experiences are recognized as important determinants for adolescent psychiatric health in general, our objective was to explore the specific influence of childhood bereavement on the stress resilience development trajectory. Methods In this national register-based cohort study, we identified 407,639 men born in Sweden between 1973 and 1983, who underwent compulsory military enlistment examinations in late adolescence, including measures of psychological stress resilience. We defined exposure as loss of a first-degree family member in childhood, and estimated relative risk ratios (RRRs) for reduced (moderate or low), compared with high, stress resilience with 95% confidence intervals (CIs) using multinomial logistic regression. Results Loss of a parent or sibling in childhood conferred a 49% increased risk of subsequent low stress resilience (RRR, 1.49, 95% CI, 1.41–1.57) and an 8% increased risk of moderate stress resilience (RRR, 1.08, 95% CI, 1.03–1.13) in late adolescence. There was also a graded increase in risk with increasing age at loss; teenagers were at higher risk for low resilience (RRR, 1.64, 95% CI, 1.52–1.77) than children aged 7–12 (RRR, 1.47, 95% CI, 1.34–1.61) and ≤6 years (RRR, 1.16 95% CI, 1.02–1.32). The excess risk was observed for all causes of death, including suicide and unexpected deaths as well as deaths due to other illnesses. The associations remained after exclusion of parents with a history of hospitalization for psychiatric diagnoses. Conclusions The long-term consequences of childhood bereavement may include lower stress resilience in late adolescence.

Although smoking during pregnancy may lead to many adverse outcomes, numerous studies have reported a paradoxical inverse association between maternal cigarette smoking during pregnancy and preeclampsia. Using a counterfactual framework we aimed to explore the structure of this paradox as being a consequence of selection bias. Using a case-control study nested in the Icelandic Birth Registry (1309 women), we show how this selection bias can be explored and corrected for. Cases were defined as any case of pregnancy induced hypertension or preeclampsia occurring after 20 weeks' gestation and controls as normotensive mothers who gave birth in the same year. First, we used directed acyclic graphs to illustrate the common bias structure. Second, we used classical logistic regression and mediation analytic methods for dichotomous outcomes to explore the structure of the bias. Lastly, we performed both deterministic and probabilistic sensitivity analysis to estimate the amount of bias due to an uncontrolled confounder and corrected for it. The biased effect of smoking was estimated to reduce the odds of preeclampsia by 28 % (OR 0.72, 95 %CI 0.52, 0.99) and after stratification by gestational age at delivery (<37 vs. ≥37 gestation weeks) by 75 % (OR 0.25, 95 %CI 0.10, 0.68). In a mediation analysis, the natural indirect effect showed and OR > 1, revealing the structure of the paradox. The bias-adjusted estimation of the smoking effect on preeclampsia showed an OR of 1.22 (95 %CI 0.41, 6.53). The smoking-preeclampsia paradox appears to be an example of (1) selection bias most likely caused by studying cases prevalent at birth rather than all incident cases from conception in a pregnancy cohort, (2) omitting important confounders associated with both smoking and preeclampsia (preventing the outcome to develop) and (3) controlling for a collider (gestation weeks at delivery). Future studies need to consider these aspects when studying and interpreting the association between smoking and pregnancy outcomes.

<b>Objective</b>&nbsp;To examine the relative risks of iatrogenic and non-iatrogenic injuries during the period shortly before and after a diagnosis of cancer. <b>Design</b>&nbsp;Nationwide register based study. <b>Setting</b>&nbsp;Swedish national population and health registers. <b>Participants</b>&nbsp;720 901 patients with diagnosis of cancer, 1991-2009, in Sweden. <b>Main outcome measures</b>&nbsp;All hospital admissions in patients with cancer with a main discharge diagnosis of iatrogenic (from medical complications) or non-iatrogenic injuries in 1990-2010 identified from the Swedish patient register. Conditional Poisson regression was used to compare the incidence rate of injuries during the “diagnostic period” (16 weeks before to 16 weeks after diagnosis) with the incidence rate during a “pre-diagnostic period” (the same 32 weeks one year before diagnosis) among the same patients. <b>Results</b>&nbsp;During the diagnostic period, there were 7306 iatrogenic (incidence rate 0.60 per 1000 person months) and 8331 non-iatrogenic injuries (incidence rate 0.69 per 1000 person months). For iatrogenic injuries, the incidence rate ratio was 7.0 (95% confidence interval 6.6 to 7.4) during the diagnostic period compared with the pre-diagnostic period. The increase in risk started two weeks before cancer diagnosis and peaked during the two weeks after diagnosis (48.6, 37.3 to 63.5). For non-iatrogenic injuries, the incidence rate ratio was 1.9 (1.8 to 2.0) during the diagnostic period compared with the pre-diagnostic period. The increase in risk began four weeks before diagnosis and peaked during the two weeks before diagnosis (5.3, 4.6 to 6.1). There were increased risks of both types of injury during the diagnostic period for all common cancers, with the smallest risk increase noted for non-melanoma skin cancer. <b>Conclusions</b>&nbsp;Patients with cancer have highly increased risks of both iatrogenic and non-iatrogenic injuries requiring inpatient care<b></b>shortly before and after their diagnosis. These findings shed further light on the total burden of medical complications and call for prevention of intentional and unintentional injuries during the diagnostic process of cancer.

Abstract Background Cancer patients have a highly increased risk of psychiatric disorders following diagnosis, compared with cancer-free individuals. Inflammation is involved in the development of both cancer and psychiatric disorders. The role of non-steroidal anti-inflammatory drugs (NSAIDs) in the subsequent risk of psychiatric disorders after cancer diagnosis is however unknown. Methods We performed a cohort study of all patients diagnosed with a first primary malignancy between July 2006 and December 2013 in Sweden. Cox proportional hazards models were used to assess the association of NSAID use during the year before cancer diagnosis with the risk of depression, anxiety, and stress-related disorders during the first year after cancer diagnosis. Results Among 316,904 patients identified, 5613 patients received a diagnosis of depression, anxiety, or stress-related disorders during the year after cancer diagnosis. Compared with no use of NSAIDs, the use of aspirin alone was associated with a lower rate of depression, anxiety, and stress-related disorders (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.81 to 0.97), whereas the use of non-aspirin NSAIDs alone was associated with a higher rate (HR, 1.24; 95% CI, 1.15 to 1.32), after adjustment for sociodemographic factors, comorbidity, indications for NSAID use, and cancer characteristics. The association of aspirin with reduced rate of depression, anxiety, and stress-related disorders was strongest for current use (HR, 0.84; 95% CI, 0.75 to 0.93), low-dose use (HR, 0.88; 95% CI, 0.80 to 0.98), long-term use (HR, 0.84; 95% CI, 0.76 to 0.94), and among patients with cardiovascular disease (HR, 0.81; 95% CI, 0.68 to 0.95) or breast cancer (HR, 0.74; 95% CI, 0.56 to 0.98). Conclusion Pre-diagnostic use of aspirin was associated with a decreased risk of depression, anxiety, and stress-related disorders during the first year following cancer diagnosis.

Background: β-adrenergic signaling has been implicated in the pathology of hepatocellular carcinoma (HCC), but the evidence from clinical studies is limited. In this national population-based cohort study, we investigated the possible association of β-adrenergic receptor blockers and cancer-specific mortality among patients with primary HCC diagnosed in Sweden between 2006 and 2014.Methods: Patients were identified from the Swedish Cancer Register (n = 2104) and followed until 31 December 2015. We used Cox regression to evaluate the association of β-blockers dispensed within 90 days prior to cancer diagnosis, ascertained from the national Prescribed Drug Register, with liver cancer mortality identified from the Cause of Death Register, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and treatment procedures.Results: Over a median follow-up of 9.9 months, 1601 patients died (of whom 1309 from liver cancer). Compared with non-use, β-blocker use at cancer diagnosis [n = 714 (predominantly prevalent use, 93%)] was associated with lower liver cancer mortality [0.82 (0.72–0.94); p = .005]. Statistically significant associations were observed for non-selective [0.71 (0.55–0.91); p = .006], β1-receptor selective [0.86 [0.75–1.00); p = .049] and lipophilic [0.78 (0.67–0.90); p = .001] β-blockers. No association was observed for hydrophilic β-blockers [1.01 (0.80–1.28); p = .906] or other antihypertensive medications. Further analysis suggested that the observed lower liver cancer mortality rate was limited to patients with localized disease at diagnosis [0.82 (0.67–1.01); p = .062].Conclusion: β-blocker use was associated with lower liver cancer mortality rate in this national cohort of patients with HCC. A higher-magnitude inverse association was observed in relation to non-selective β-blocker use.