Suicide attempt and death by suicide among parents of young individuals with cancer: A population-based study in Denmark and Sweden.

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

Estrogen-modulating treatment among mid-life women and COVID-19 morbidity and mortality: a multiregister nationwide matched cohort study in Sweden.

BACKGROUND: It has been repeatedly shown that men infected by SARS-CoV-2 face a twofold higher likelihood of dying, being hospitalized or admitted to the intensive care unit compared to women, despite taking into account relevant confounders. It has been hypothesized that these discrepancies are related to sex steroid hormone differences with estrogens being negatively correlated with disease severity. The objective of this study was therefore to evaluate COVID-19-related mortality and morbidity among peri- and postmenopausal women in relation to estrogen-containing menopause hormonal treatments (MHT). METHODS: This is a national register-based matched cohort study performed in Sweden between January 1 to December 31, 2020. Study participants comprised women over the age of 53 years residing in Sweden. Exposure was defined as prescriptions of local estrogens, systemic estrogens with and without progestogens, progestogens alone, or tibolone. MHT users were then compared with a matched cohort of non-users. The primary outcome consisted of COVID-19 mortality, whereas the secondary outcomes included inpatient hospitalizations/outpatient visits and confirmed SARS-CoV-2 infection. Multivariable adjusted Cox regression-derived hazard ratios (HRs) were calculated. RESULTS: Use of systemic estrogens alone is associated with increased COVID-19 mortality among older women (aHR 4.73, 1.22 to 18.32), but the association is no longer significant when discontinuation of estrogen use is accounted for. An increased risk for COVID-19 infection is further observed for women using combined systemic estrogens and progestogens (aHR 1.06, 1.00 to 1.13) or tibolone (aHR 1.21, 1.01 to 1.45). Use of local estrogens is associated with an increased risk for COVID-19-related death (aHR 2.02,1.45 to 2.81) as well as for all secondary outcomes. CONCLUSIONS: Systemic or local use of estrogens does not decrease COVID-19 morbidity and mortality to premenopausal background levels. Excess risk for COVID-19 morbidity and mortality was noted among older women and those discontinuing systemic estrogens. Higher risk for death was also noted among women using local estrogens, for which non-causal mechanisms such as confounding by comorbidity or frailty seem to be the most plausible underlying explanations. TRIAL REGISTRATION DETAILS: Not applicable.

Association between electroconvulsive therapy and time to readmission after a manic episode.

OBJECTIVE: The majority of patients hospitalized for treatment of a manic episode are readmitted within 2 years despite maintenance treatment. Electroconvulsive therapy (ECT) has been associated with lower rehospitalization rates in some psychiatric conditions, but its association with readmission after a manic episode has not been investigated. Therefore, the aim of this study was to determine whether the time to readmission in patients with mania treated with ECT was longer than in patients not treated with ECT and whether there were subgroups of patients that benefited more. METHODS: This was a nationwide register-based, observational study. All patients diagnosed with bipolar disorder, manic episode, admitted to any hospital in Sweden between 2012 and 2021 were included. Patients contributed data to the study for every admission. All admissions were followed up until psychiatric readmission, death, or the end of the study (December 31, 2021). Association between ECT and time to readmission was analyzed. A paired samples model was performed for 377 patients with at least two admissions for mania, treated with ECT at one admission and without ECT at the other admission. Times to readmission were analyzed. RESULTS: A total of 12,337 admissions were included; mean (SD) age 47.7 (17.2), 5443 (44.1%) men. Readmission rate within 1 year was 54.6%. ECT was administered in 902 (7.3%) admissions. Within 30 days after admission, 182 out of 894 (20.4%) patients treated with ECT versus 2105 out of 11,305 (18.6%) patients treated without ECT were readmitted. There was no association between ECT and time to readmission (aHR 1.00, 95% CI 0.86-1.16, p = 0.992) in the model with all admissions. The paired samples model included 754 admissions (377 patients), mean (SD) age during admission without ECT was 45.6 (16.5), and with ECT 46.6 (16.4), 147 (39.0%) were men. In that model, readmission rate within 30 days for treatment with ECT was 19.0%, and for treatments without ECT, 24.1% (aHR 0.75, 95% CI 0.55-1.02, p = 0.067). CONCLUSION: Readmission rates after inpatient treatment of mania were high. ECT was not significantly associated with longer time to readmission, but there was a trend toward a protective effect of ECT when admissions with and without ECT were compared within the same patients.

Androgen deprivation therapy in men with prostate cancer is not associated with COVID-2019 infection.

BACKGROUND: Androgens may play a role in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and host responses as the virus is dependent on the androgen-regulated protein transmembrane serine protease 2 for cell entry. Studies have indicated that prostate cancer patients receiving androgen deprivation therapy (ADT) are at reduced risk of SARS-CoV-2 infection and serious complications compared with patients without ADT, but data are inconsistent. METHODS: A total of 655 prostate cancer patients who were under surveillance at two urology departments in Sweden on April 1, 2020 were included in the study as well as 240 patients with benign prostatic hyperplasia (BPH). At follow-up early in 2021, the participants completed a questionnaire containing information about symptoms compatible with coronavirus disease 2019 (COVID-19). Blood samples were also collected for the assessment of SARS-CoV-2 IgG antibodies (SARS-CoV-2 Total; Siemens). We used multivariable logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between ADT and the risk of SARS-CoV-2 infection. RESULTS: The cumulative incidence of SARS-CoV-2 seropositivity was 13.4% among patients receiving ADT and 10.4% among patients without ADT. After adjusting for potential confounders, we observed no differences in symptoms or risk of SARS-CoV-2 infection between patients with and without ADT (OR: 0.98; 95% CI: 0.52-1.85). Higher body mass index, Type 1 diabetes, and prostate cancer severity, defined by high Gleason score (8-10; OR: 2.06; 95% CI: 1.04-4.09) or elevated levels of prostate-specific antigen (>20 µg/l; OR: 2.15; 95% CI: 1.13-4.07) were associated with increased risk of SARS-CoV-2 infection. Overall, the risk of SARS-CoV-2 infection was not higher among men with prostate cancer than among men with BPH. CONCLUSIONS: Our results do not support the hypothesis that ADT use in prostate cancer patients reduces the risk or symptom severity of SARS-CoV-2 infection or that prostate cancer patients are at increased risk of COVID-19 compared with men without prostate cancer.

Associations of parental and perinatal factors with subsequent risk of stress-related disorders: a nationwide cohort study with sibling comparison.

Little is known about the contribution of pregnancy-related parental and perinatal factors to the development of stress-related disorders. We aimed to investigate whether parental/perinatal adversities entail higher risks of stress-related disorders in the offspring, later in life, by accounting for genetic and early environmental factors. Based on the nationwide Swedish registers, we conducted a population-based cohort study of 3,435,747 singleton births (of which 2,554,235 were full siblings), born 1973-2008 and survived through the age of 5 years. Using both population- and sibling designs, we employed Cox regression to assess the association between parental and perinatal factors with subsequent risk of stress-related disorders. We identified 55,511 individuals diagnosed with stress-related disorders in the population analysis and 37,433 in the sibling analysis. In the population-based analysis we observed increased risks of stress-related disorders among offspring of maternal/paternal age <25, single mothers, parity ≥4, mothers with BMI ≥ 25 or maternal smoking in early pregnancy, gestational diabetes, and offspring born moderately preterm (GA 32-36 weeks), or small-for-gestational-age. These associations were significantly attenuated toward null in the sibling analysis. Cesarean-section was weakly associated with offspring stress-related disorders in population [hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06-1.12] and sibling analyses (HR 1.10, 95% CI 1.02-1.20). Our findings suggest that most of the observed associations between parental and perinatal factors and risk of stress-related disorders in the population analysis are driven by shared familial environment or genetics, and underscore the importance of family designs in epidemiological studies on the etiology of psychiatric disorders.

Psychobiological stress response to a lung cancer diagnosis: a prospective study of patients in Iceland and Sweden.

BACKGROUND: A diagnostic work-up leading to a lung cancer diagnosis is a severely stressful experience that may impact tumor progression. Yet, prospective data are scarce on psychological and biological components of stress at the time of lung cancer diagnosis. The aim of this study was to assess pre-to-post diagnosis change in psychological distress and urinary excretion of catecholamines in patients with suspected lung cancer. METHODS: Participants were 167 patients within the LUCASS study, recruited at referral for suspected lung cancer to University Hospitals in Iceland and Sweden. Patients completed questionnaires on perceived distress (Hospital Anxiety and Depression Scale, HADS) before and after diagnosis of lung cancer or a non-malignant origin. A subpopulation of 85 patients also provided overnight urine for catecholamine analysis before and at a median of 24 days after diagnosis but before treatment. RESULTS: A lung cancer diagnosis was confirmed in 123 (73.7%) patients, with a mean age of 70.1 years. Patients diagnosed with lung cancer experienced a post-diagnosis increase in psychological distress (p = 0.010), while patients with non-malignant lung pathology showed a reduction in distress (p = 0.070). Both urinary epinephrine (p = 0.001) and norepinephrine (p = 0.032) levels were higher before the diagnosis among patients eventually diagnosed with lung cancer compared to those with non-malignant lung pathology. We observed indications of associations between pre-to-post diagnosis changes in perceived distress and changes in urinary catecholamine levels. CONCLUSION: Receiving a lung cancer diagnosis is associated with an increase in psychological distress, while elevated catecholamine levels are evident already before lung cancer diagnosis.

Visual Acuity and the Risk of Cycling Injuries: Register-Based Cohort Study From Adolescence to Middle-age.

BACKGROUND: Cycling is increasingly encouraged in many countries as an inexpensive and healthy choice of transportation. Operating any vehicle on the road requires high visual acuity, but few studies to our knowledge have examined the association between vision and cycling injuries. METHODS: We examined whether poorer visual acuity is associated with increased risk of fatal and nonfatal cycling injuries. We used prospectively recorded register data for 691,402 men born between 1970 and 1992 in Sweden. We followed these men from an average age of 18 years, when visual acuity was assessed during the conscription assessment, to age 45 at the latest. We identified fatal and nonfatal cycling and car injuries using Patient and Cause of Death registers. Cox regression models were used to estimate hazard ratios and 95% confidence intervals. RESULTS: Based on visual acuity for the eye with the best vision, moderately impaired acuity 0.9 to 0.6 when wearing refractive correction was associated with increased risk for cycling injuries (hazard ratio = 1.44 [95% confidence interval = 1.16, 1.79]) compared with unimpaired vision (uncorrected visual acuity 1.0) and after adjustment for a wide range of potential confounders. This association remained consistent across various sensitivity analyses. Visual acuity was not associated with car injury risk. CONCLUSIONS: In this cohort study, poorer vision was specifically associated with a higher rate of cycling injuries.

NSAID use and unnatural deaths after cancer diagnosis: a nationwide cohort study in Sweden.

BACKGROUND: Cancer patients experience increased risk of death from accident and suicide. Cognitive impairment induced by cancer-related inflammation and stress-related psychiatric symptoms may be underlying mechanisms. We therefore studied the association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of these outcomes. METHODS: Following a cohort of 388,443 cancer patients diagnosed between October 2005 and December 2014 in Sweden, we ascertained dispense of aspirin or non-aspirin NSAIDs from 3 months before cancer diagnosis onward and defined the on-medication period as from date of drug dispense until the prescribed dosage was consumed. Follow-up time outside medicated periods and time from unexposed patients were defined as off-medication periods. We used Cox models to estimate hazard ratios (HRs) of death due to suicide or accident, by comparing the on-medication periods with off-medication periods. RESULTS: In total, 29.7% of the cancer patients had low-dose aspirin dispensed and 29.1% had non-aspirin NSAIDs dispensed. Patients with aspirin use were more likely to be male than patients without aspirin use. Compared with off-medication periods, there was a 22% lower risk of accidental death (N = 651; HR 0.78, 95% confidence interval [CI]: 0.70 to 0.87) during on-medication periods with aspirin. The use of aspirin was not associated with risk of suicide (N = 59; HR 0.96, 95% CI: 0.66 to 1.39). No association was noted between use of non-aspirin NSAIDs and the risk of suicide (N = 13; HR 0.95, 95% CI: 0.42 to 2.18) or accidental death (N = 59; HR 0.92, 95% CI: 0.68 to 1.26). CONCLUSIONS: Intake of low-dose aspirin after cancer diagnosis was associated with a lower risk of unnatural deaths among cancer patients.

Neuroendocrine pathways and breast cancer progression: a pooled analysis of somatic mutations and gene expression from two large breast cancer cohorts.

BACKGROUND: Experimental studies indicate that neuroendocrine pathways might play a role in progression of breast cancer. We aim to test the hypothesis that somatic mutations in the genes of neuroendocrine pathways influence breast cancer prognosis, through dysregulated gene expression in tumor tissue. METHODS: We conducted an extreme case-control study including 208 breast cancer patients with poor invasive disease-free survival (iDFS) and 208 patients with favorable iDFS who were individually matched on molecular subtype from the Breast Cancer Cohort at West China Hospital (WCH; N = 192) and The Cancer Genome Atlas (TCGA; N = 224). Whole exome sequencing and RNA sequencing of tumor and paired normal breast tissues were performed. Adrenergic, glucocorticoid, dopaminergic, serotonergic, and cholinergic pathways were assessed for differences in mutation burden and gene expression in relation to breast cancer iDFS using the logistic regression and global test, respectively. RESULTS: In the pooled analysis, presence of any somatic mutation (odds ratio = 1.66, 95% CI: 1.07-2.58) of the glucocorticoid pathway was associated with poor iDFS and a two-fold increase of tumor mutation burden was associated with 17% elevated odds (95% CI: 2-35%), after adjustment for cohort membership, age, menopausal status, molecular subtype, and tumor stage. Differential expression of genes in the glucocorticoid pathway in tumor tissue (P = 0.028), but not normal tissue (P = 0.701), was associated with poor iDFS. Somatic mutation of the adrenergic and cholinergic pathways was significantly associated with iDFS in WCH, but not in TCGA. CONCLUSION: Glucocorticoid pathway may play a role in breast cancer prognosis through differential mutations and expression. Further characterization of its functional role may open new avenues for the development of novel therapeutic targets for breast cancer.

Public awareness, emotional reactions and human mobility in response to the COVID-19 outbreak in China - a population-based ecological study.

BACKGROUND: The outbreak of COVID-19 generated severe emotional reactions, and restricted mobility was a crucial measure to reduce the spread of the virus. This study describes the changes in public emotional reactions and mobility patterns in the Chinese population during the COVID-19 outbreak. METHODS: We collected data on public emotional reactions in response to the outbreak through Weibo, the Chinese Twitter, between 1st January and 31st March 2020. Using anonymized location-tracking information, we analyzed the daily mobility patterns of approximately 90% of Sichuan residents. RESULTS: There were three distinct phases of the emotional and behavioral reactions to the COVID-19 outbreak. The alarm phase (19th-26th January) was a restriction-free period, characterized by few new daily cases, but a large amount public negative emotions [the number of negative comments per Weibo post increased by 246.9 per day, 95% confidence interval (CI) 122.5-371.3], and a substantial increase in self-limiting mobility (from 45.6% to 54.5%, changing by 1.5% per day, 95% CI 0.7%-2.3%). The epidemic phase (27th January-15th February) exhibited rapidly increasing numbers of new daily cases, decreasing expression of negative emotions (a decrease of 27.3 negative comments per post per day, 95% CI -40.4 to -14.2), and a stabilized level of self-limiting mobility. The relief phase (16th February-31st March) had a steady decline in new daily cases and decreasing levels of negative emotion and self-limiting mobility. CONCLUSIONS: During the COVID-19 outbreak in China, the public's emotional reaction was strongest before the actual peak of the outbreak and declined thereafter. The change in human mobility patterns occurred before the implementation of restriction orders, suggesting a possible link between emotion and behavior.

Beta-blocker use and urothelial bladder cancer survival: a Swedish register-based cohort study.

BACKGROUND: Recent observational studies linked ß-adrenergic receptor blocker use with improved survival in patients with several cancer types, but there is no information on the potential effects of ß-blockers in patients with bladder cancer. Literature from pre-clinical studies is also limited, but urothelial cancer can exhibit significant overexpression of ß-adrenergic receptors relative to normal urothelial tissue, suggesting that urothelial cancer may benefit from ß-blockade therapy. We thus aimed to explore the possible association between ß-blocker use and bladder cancer-specific mortality (BCSM) among patients with urothelial bladder cancer. MATERIAL AND METHODS: Patients diagnosed during 2006-2014 and identified from the Swedish Cancer Register (n = 16,669) were followed until 31 December 2015. Cox regression was used to evaluate the association of ß-blockers dispensed within 90 days prior to cancer diagnosis with BCSM (primary outcome) and all-cause mortality, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and surgical procedures. Hazard ratios (HR) with 95% confidence intervals (CI) were reported. RESULTS: Overall, ß-blocker use was associated with lower BCSM [HR 0.88 (95%CI 0.81-0.96)]. Especially use of nonselective ß-blockers showed a clear inverse association in comparison with both nonuse [0.66 (0.50-0.86)] and use of other antihypertensive medications [0.72 (0.54-0.95)]. The inverse association was most pronounced among patients with locally advanced/metastatic disease: [0.35 (0.18-0.68)]. A lower-magnitude inverse association was observed for selective ß-blocker use [0.91 (0.83-0.99)]. Largely similar inverse associations were observed for hydrophilic [0.82 (0.70-0.95)] and lipophilic [0.91 (0.83-1.00)] ß-blocker use. CONCLUSION: ß-blocker use, particularly of the nonselective type, was associated with lower BCSM, especially in patients with locally advanced/metastatic urothelial bladder cancer.

Optimal communication associated with lower risk of acute traumatic stress after lung cancer diagnosis.

PURPOSE: The aim of this study was to assess the role of the patient's background and perceived healthcare-related factors in symptoms of acute stress after lung cancer diagnosis. METHODS: The study population consisted of 89 individuals referred for diagnostic work-up at Landspitali National University Hospital in Iceland and subsequently diagnosed with lung cancer. Before diagnosis, the patients completed questionnaires on sociodemographic characteristics, pre-diagnostic distress (Hospital Anxiety and Depression Scale), social support, and resilience. At a median of 16 days after diagnosis, the patients reported symptoms of acute stress on the Impact of Event Scale-Revised (IES-R) and experience of communication and support from healthcare professionals and family during the diagnostic period. RESULTS: Patients were on average 68 years and 52% reported high levels of post-diagnostic acute stress (IES-R > 23) while 24% reported symptoms suggestive of clinical significance (IES-R > 32). Prior history of cancer (ß = 6.7, 95% CI: 0.1 to 13.3) and pre-diagnostic distress were associated with higher levels of post-diagnostic acute stress (ß = 8.8, 95% CI: 2.7 to 14.9), while high educational level (ß = - 7.9, 95% CI: - 14.8 to - 1.1) was associated with lower levels. Controlling for the abovementioned factors, the patients' perception of optimal doctor-patient (ß = - 9.1, 95% CI: - 14.9 to - 3.3) and family communication (ß = - 8.6, 95% CI: - 14.3 to - 2.9) was inversely associated with levels of post-diagnostic acute stress after lung cancer diagnosis. CONCLUSIONS: A high proportion of patients with newly diagnosed lung cancer experience high levels of acute traumatic stress of potential clinical significance. Efforts to improve doctor-patient and family communication may mitigate the risk of these adverse symptoms.

Public health insurance and cancer-specific mortality risk among patients with breast cancer: A prospective cohort study in China.

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.

Proton pump inhibitors and survival in patients with colorectal cancer: a Swedish population-based cohort study.

BACKGROUND: Proton pump inhibitors (PPIs) are associated with microbiome changes of the gut, which in turn may affect the progression of colorectal cancer (CRC). This study aims to assess the associations between PPI use and all-cause and CRC-specific mortality. METHODS: We selected all patients registered in the Swedish Prescribed Drug Registry who were diagnosed with CRC between 2006 and 2012 (N = 32,411, 54.9% PPI users) and subsequently followed them through register linkage to the Swedish Causes of Death Registry until December 2013. PPI users were patients with ≥1 post-diagnosis PPI dispensation. Time-dependent Cox-regression models were performed with PPI use as time-varying exposure. RESULTS: Overall 4746 (14.0%) patients died, with an aHR of 1.38 (95% CI 1.32-1.44) for all-cause mortality comparing PPI users with PPI nonusers. Higher-magnitude associations were observed among male, cancer stage 0-I, rectal cancer and patients receiving CRC surgery. The PPI-all-cause mortality association was also more pronounced comparing new users to non-users (aHR = 1.47, 95%CI 1.40-1.55) than comparing continuous users to non-users (aHR = 1.32, 95%CI 1.24-1.39). The risk estimates for CRC-specific mortality comparing PPI users to PPI nonusers were similar to those for all-cause mortality. CONCLUSION: PPI use after the CRC diagnosis was associated with increased all-cause and CRC-specific mortality.

Cardiovascular mortality among cancer survivors who developed breast cancer as a second primary malignancy.

BACKGROUND: To assess the risk of cardiovascular mortality among cancer survivors who developed breast cancer as a second malignancy (BCa-2) compared with patients with first primary breast cancer (BCa-1) and the general population. METHODS: Using the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study including 1,024,047 BCa-1 and 41,744 BCa-2 patients diagnosed from the age 30 between 1975 and 2016, and the corresponding US female population (994,415,911 person-years; 5,403,551 cardiovascular deaths). Compared with the general population and BCa-1 patients, we calculated incidence rate ratios (IRRs) of cardiovascular deaths among BCa-2 patients using Poisson regression. To adjust for unmeasured confounders, we performed a nested, case-crossover analysis among BCa-2 patients who died from cardiovascular disease. RESULTS: Although BCa-2 patients had a mildly increased risk of cardiovascular mortality compared with the population (IRR 1.08) and BCa-1 patients (IRR 1.15), the association was pronounced among individuals aged 30-49 years (BCa-2 vs. population: IRR 6.61; BCa-2 vs. BCa-1: IRR 3.03). The risk elevation was greatest within the first month after diagnosis, compared with the population, but comparable with BCa-1 patients. The case-crossover analysis confirmed these results. CONCLUSION: Our findings suggest that patients with BCa-2 are at increased risk of cardiovascular mortality.

Psychological distress among health professional students during the COVID-19 outbreak.

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.

Prediagnostic use of estrogen-only therapy is associated with improved colorectal cancer survival in menopausal women: a Swedish population-based cohort study.

BACKGROUND: Menopausal hormone therapy (MHT) reduces the risk of developing colorectal cancer (CRC), yet it is largely unclear whether it could also influence survival in women with CRC. Therefore, we aimed to investigate the influence of prediagnostic MHT use on CRC-specific and all-cause mortality in women with CRC. METHODS: This nationwide nested cohort study, within a large population-based matched cohort, included all women diagnosed with incident CRC between January 2006 and December 2012 (N = 7814). A total of 1529 women had received at least one dispensed prescription of systemic MHT before CRC diagnosis, and 6285 CRC women with CRC did not receive MHT during the study period, as ascertained from the Swedish Prescribed Drug Registry. Multivariable Cox regression models provided adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for CRC-specific mortality and all-cause mortality. RESULTS: Past use of prediagnostic estrogen-only therapy (E-MHT) was associated with lower CRC-specific (HR = 0.67, 95%CI 0.44-0.99) and all-cause mortality (HR = 0.68, 95%CI 0.59-0.93). However, all-cause mortality (HR = 1.23, 95%CI 1.02-1.48) was elevated among current prediagnostic E-MHT users who were 70+ years at diagnosis. Current estrogen combined progestin therapy (EP-MHT) was associated with higher CRC-specific mortality (HR = 1.61, 95%CI 1.06-2.44) in older women, but no association was shown for all-cause mortality. CONCLUSIONS: Our findings suggest that E-MHT, but not EP-MHT use, might be associated with improved CRC survival, indicating a potential role of estrogens in sex hormone-related cancers. However, association of MHT use with grade of cancer remains unclear.

Validity of Routinely Collected Swedish Data in the International Enhanced Recovery After Surgery (ERAS) Database.

BACKGROUND: This study aims to assess patient coverage, validity and data quality in the Swedish part of the International Enhanced Recovery After Surgery (ERAS) Interactive Audit System (EIAS). METHOD: All Swedish ERAS centers that recorded colorectal surgery data in EIAS between January 1, 2017, and December 31, 2017, were included (N = 12). Information registered in EIAS was compared with data from electronic medical records at each hospital to assess the overall coverage of EIAS. Twenty random-selected patients from each of the contributing centers were assessed for accuracy for a set of clinically relevant variables. All patients admitted to the contributing centers were included for the assessment of rate of missing on a selection of key clinical variables. RESULTS: Eight hospitals provided complete information for the evaluation, while four hospitals only allowed assessment of coverage and missing data. The eight hospitals had an overall coverage of 98.8% in EIAS (n = 1301) and the four 86.7% (n = 811). The average agreement for the assessed postoperative outcome variables was 96.5%. The accuracy was excellent for 'length of hospital stay,' 'reoperation,' and 'any complications,' but lower for other types of complications. Only a few variables had more than 5% missing data, and missingness was associated with hospital type and size. CONCLUSION: This validation of the Swedish part of the international ERAS database suggests high patient coverage in EIAS and high agreement and limited missingness in clinically relevant variables. This validation approach or a modified version can be used for continued validation of the International ERAS database.

Pregnancy As a Risk Factor for Small Bowel Obstruction After Laparoscopic Gastric Bypass Surgery.

OBJECTIVE: To evaluate whether pregnancy is associated with increased risk for small bowel obstruction after laparoscopic gastric bypass surgery. BACKGROUND: Small bowel obstruction is a common and feared long-term complication to laparoscopic gastric bypass surgery that may be more common during pregnancy. It is unclear if the risk truly increases during pregnancy. METHODS: Women, 18 to 55 years, operated with a primary laparoscopic gastric bypass procedure from 2010 until 2015 were identified through the Scandinavian Obesity Surgery Registry (n = 25,853). Through record-linkage to the Medical Birth Registry, the National Patient Registry, and review of hospital charts, information on pregnancy periods and outcome were obtained. The main outcome was operation due to small bowel obstruction after the laparoscopic gastric bypass procedure. RESULTS: Pregnancy was associated with increased risk for small bowel obstruction following laparoscopic gastric bypass surgery (incidence rates 46.5, 95% CI 38.0-56.9/1000 person-years, vs 20.9 95% CI 19.9-22.0; adjusted-HR 1.72, 95% CI 1.39-2.12, P < 0.001). While no excess risk was observed during the first trimester, the second (adjusted-HR 1.67, 95% CI 1.17-2.39, P = 0.005) and third (adjusted-HR 2.69, 95% CI 2.02-3.59, P < 0.001) conferred increased risk. The incidence rate of small bowel obstruction during pregnancy was 42.9 (95% CI 32.4-57.0/1000 person-years) among women for whom the mesenteric defects had been closed during the primary procedure, and 53.2 (95% CI 38.9-72.8/1000 person-years) for women in whom they had been left open. CONCLUSION: Pregnancy is associated with increased risk for small bowel obstruction after laparoscopic gastric bypass surgery during the second and third trimesters.

Aspirin and other non-steroidal anti-inflammatory drugs and depression, anxiety, and stress-related disorders following a cancer diagnosis: a nationwide register-based cohort study.

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.