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Objectives Firefighters are potentially exposed to a wide range of known and suspected carcinogens through their work. The objectives of this study were to examine the patterns of cancer among Nordic firefighters, and to compare them with the results from previous studies. Methods Data for this study were drawn from a linkage between the census data for 15 million people from the five Nordic countries and their cancer registries for the period 1961–2005. SIR analyses were conducted with the cancer incidence rates for the entire national study populations used as reference rates. Results A total of 16 422 male firefighters were included in the final cohort. A moderate excess risk was seen for all cancer sites combined, (SIR=1.06, 95% CI 1.02 to 1.11). There were statistically significant excesses in the age category of 30–49 years in prostate cancer (SIR=2.59, 95% CI 1.34 to 4.52) and skin melanoma (SIR=1.62, 95% CI 1.14 to 2.23), while there was almost no excess in the older ages. By contrast, an increased risk, mainly in ages of 70 years and higher, was observed for non-melanoma skin cancer (SIR=1.40, 95% CI 1.10 to 1.76), multiple myeloma (SIR=1.69, 95% CI 1.08 to 2.51), adenocarcinoma of the lung (SIR=1.90, 95% CI 1.34 to 2.62), and mesothelioma (SIR=2.59, 95% CI 1.24 to 4.77). By contrast with earlier studies, the incidence of testicular cancer was decreased (SIR=0.51, 95% CI 0.23 to 0.98). Conclusions Some of these associations have been observed previously, and potential exposure to polycyclic aromatic hydrocarbons, asbestos and shift work involving disruption of circadian rhythms may partly explain these results.

In severe viral pneumonia, including Coronavirus disease 2019 (COVID-19), the viral replication phase is often followed by hyperinflammation, which can lead to acute respiratory distress syndrome, multi-organ failure, and death. We previously demonstrated that alpha-1 adrenergic receptor (⍺ 1 -AR) antagonists can prevent hyperinflammation and death in mice. Here, we conducted retrospective analyses in two cohorts of patients with acute respiratory distress (ARD, n = 18,547) and three cohorts with pneumonia (n = 400,907). Federated across two ARD cohorts, we find that patients exposed to ⍺ 1 -AR antagonists, as compared to unexposed patients, had a 34% relative risk reduction for mechanical ventilation and death (OR = 0.70, p = 0.021). We replicated these methods on three pneumonia cohorts, all with similar effects on both outcomes. All results were robust to sensitivity analyses. These results highlight the urgent need for prospective trials testing whether prophylactic use of ⍺ 1 -AR antagonists ameliorates lower respiratory tract infection-associated hyperinflammation and death, as observed in COVID-19.

Objective To study the long term risk of invasive cancer of the cervix or vagina after treatment for cervical intraepithelial neoplasia grade 3.Design Prospective cohort study.Setting Swedish cancer registry.Participants All women in Sweden with severe dysplasia or cervical carcinoma in situ (equivalent to cervical intraepithelial neoplasia grade 3) treated during 1958-2002 (n=132 493) contributing 2 315 724 woman years.Main outcome measures Standardised incidence ratios with risk of cancer in the Swedish general female population as reference, and relative risks in multivariable log-linear regression model, with internal references.Results Women with previous cervical intraepithelial neoplasia grade 3 had an increased risk of invasive cervical cancer compared with the general female population (standardised incidence ratio 2.34, 95% confidence interval 2.18 to 2.50). The increased risk showed a decreasing trend with time since diagnosis for women treated later than 1970 but the risk was still increased after 25 years. An effect of age was found, with an accentuated increase in risk for women aged more than 50. The excess risk for cervical cancer associated with previous cervical intraepithelial neoplasia grade 3 has steadily increased since 1958. For vaginal cancer the standardised incidence ratio was 6.82 (5.61 to 8.21) but this decreased to 2.65 after 25 years. Adjustments in the multivariable log-linear regression model did not substantially alter these results.Conclusions Women previously treated for cervical intraepithelial neoplasia grade 3 are at an increased risk of developing invasive cervical cancer and vaginal cancer. This risk has increased since the 1960s and is accentuated in women aged more than 50. The risk is still increased 25 years after treatment.

The efficacy and effectiveness of the quadrivalent human papillomavirus (HPV) vaccine in preventing high-grade cervical lesions have been shown. However, data to inform the relationship between quadrivalent HPV vaccination and the subsequent risk of invasive cervical cancer are lacking. We used nationwide Swedish demographic and health registers to follow an open population of 1,672,983 girls and women who were 10 to 30 years of age from 2006 through 2017. We assessed the association between HPV vaccination and the risk of invasive cervical cancer, controlling for age at follow-up, calendar year, county of residence, and parental characteristics, including education, household income, mother's country of birth, and maternal disease history. During the study period, we evaluated girls and women for cervical cancer until their 31st birthday. Cervical cancer was diagnosed in 19 women who had received the quadrivalent HPV vaccine and in 538 women who had not received the vaccine. The cumulative incidence of cervical cancer was 47 cases per 100,000 persons among women who had been vaccinated and 94 cases per 100,000 persons among those who had not been vaccinated. After adjustment for age at follow-up, the incidence rate ratio for the comparison of the vaccinated population with the unvaccinated population was 0.51 (95% confidence interval [CI], 0.32 to 0.82). After additional adjustment for other covariates, the incidence rate ratio was 0.37 (95% CI, 0.21 to 0.57). After adjustment for all covariates, the incidence rate ratio was 0.12 (95% CI, 0.00 to 0.34) among women who had been vaccinated before the age of 17 years and 0.47 (95% CI, 0.27 to 0.75) among women who had been vaccinated at the age of 17 to 30 years. Among Swedish girls and women 10 to 30 years old, quadrivalent HPV vaccination was associated with a substantially reduced risk of invasive cervical cancer at the population level. (Funded by the Swedish Foundation for Strategic Research and others.).

In a national cohort of subjects exposed to extended-spectrum β-lactamase-producing Enterobacteriaceae (EPE), the subsequent risk of bloodstream infection by EPE declined rapidly during the first year. Several risk factors can be used to identify high-risk population subgroups. Abstract Background Little is known of the long-term risks of bloodstream infection (BSI) with extended spectrum β-lactamase-producing Enterobacteriaceae (EPE) in previously-colonized individuals. We investigated EPE-BSI risks and associated risk factors during 6 years following EPE colonization. Methods We performed a population-based cohort study in Sweden using national health registers. Subjects were followed from their first EPE finding in feces (n = 5513) or urine (n = 17189). The effects of co-morbidity, sociodemography, and outpatient antibiotic dispensation on EPE-BSI risks were assessed. The EPE-BSI risks were compared to those of 45161 matched population-based reference subjects. Results The cumulative 6-year EPE-BSI incidences were 3.8%, 1.6%, and 0.02% in the urine, feces, and reference cohorts, respectively. The incidences decreased exponentially during the first 6-12 months. Among EPE-exposed subjects, urological disorders were associated with the highest adjusted cause-specific hazard ratio (aCSHR) for subsequent EPE-BSIs (3.40, 95% confidence interval 2.47-4.69). The aCSHRs were between 1.62-2.20 for male sex, immunosuppression, diabetes, malignancy, lung disease, baseline urine source, and Klebsiella pneumoniae, compared to the Escherichia coli baseline sample. Antibiotics with selective activity against gram-negative bacilli-but mostly not EPE (trimethoprim-sulfamethoxazole, fluoroquinolones, oral cephalosporins, and penicillins with extended spectrums)-and pivmecillinam were associated with doubled EPE BSI risk during the 3 months after antibiotic dispensation in EPE-colonized subjects. Conclusions EPE in urine or feces is a substantial risk factor for subsequent EPE-BSIs, but the risk declines rapidly during the first year after detection. In EPE-colonized individuals, specific risk factors can be used to identify subgroups for targeted interventions, such as eradication therapy.

In this study of more than 6 million Swedes during 1991–2006, patients were at increased risk for suicide or death from cardiovascular causes after a diagnosis of cancer. Risks were especially high immediately after diagnosis and for cancers with a poor prognosis. Alarge body of evidence suggests high levels of distress and psychiatric symptoms among patients who receive a diagnosis of cancer. 1 – 9 Patients with cancer have been shown to be at increased risk for suicide 10 – 17 and cardiovascular events. 18 – 22 However, most results have been interpreted to be consequences of treatment or the burden of living with a progressing cancer. The psychological stress induced by the diagnosis itself may also give rise to such serious consequences. However, only a few studies have explored the period immediately after a cancer diagnosis. 13 , 14 , 23 We recently observed that patients with prostate cancer both . . .

Background. Etiologic hypotheses in infantile autism suggest a strong genetic component, as well as possible environmental risks linked to early fetal development. We evaluated the association of maternal, pregnancy, delivery, and infant characteristics and risk of infantile autism. Methods. We conducted a case-control study nested within a population-based cohort (all Swedish children born in 1974-1993). We used prospectively recorded data from the Swedish Birth Register, which were individually linked to the Swedish Inpatient Register. Cases were 408 children (321 boys and 87 girls) discharged with a main diagnosis of infantile autism from any hospital in Sweden before 10 years of age in the period 1987-1994, plus 2,040 matched controls. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results. The risk of autism was associated with daily smoking in early pregnancy (OR = 1.4; CI = 1.1-1.8), maternal birth outside Europe and North America (OR = 3.0; CI = 1.7-5.2), cesarean delivery (OR = 1.6; CI = 1.1-2.3), being small for gestational age (SGA; OR = 2.1; CI = 1.1-3.9), a 5-minute Apgar score below 7 (OR = 3.2, CI = 1.2-8.2), and congenital malformations (OR = 1.8, CI = 1.1-3.1). No association was found between autism and head circumference, maternal diabetes, being a twin, or season of birth. Conclusions. Our findings suggest that intrauterine and neonatal factors related to deviant intrauterine growth or fetal distress are important in the pathogenesis of autism.

Objective This study aimed to determine occupational variations in the incidence of breast cancer in the population-based cohort of Nordic Occupational Cancer Study (NOCCA). Methods The study included long-term follow-up data from almost 7.5 million Nordic women. Participants were assigned to one of the 54 occupational categories based on census records at the ages of 30–64 years. Sixty-two thousand cases of breast cancer were identified through record linkages between nationwide cancer registries in Finland, Sweden, Norway, Denmark, and Iceland, followed up between 1961 and 2005. Country-specific standardized incidence ratios (SIRs) with 95% confidence intervals were estimated. Results Overall, the highest risk elevations were seen among military personnel (SIR 1.58, 95% CI 1.03–2.32), dentists (SIR 1.43, 95% CI 1.31–1.56), and physicians (SIR 1.35, 95% CI 1.26–1.46). The lowest risks were observed among gardeners (SIR 0.76, 95% CI 0.74–0.78), farmers (SIR 0.80, 95% CI 0.78–0.82), and woodworkers (SIR 0.75, 95% CI 0.70–0.81). Welders, tobacco workers, and painters had higher SIRs for breast cancer diagnosed at age < 50. A reduced risk was observed among forestry workers, welders, and fishery workers for breast cancers diagnosed both before and after age 50. The SIRs for breast cancer did not vary substantially by histology. A significantly increased risk of breast cancer was observed among laboratory workers in the latest calendar period (1991–2005) compared with earlier periods (1976–1990 and 1961–1975). Occupations such as farming, forestry, driving, and gardening had low SIRs during all periods. Conclusions The study suggests that the risk of breast cancer varies by occupation. Heterogeneity is also observed in some occupational categories according to age (before or after 50), histology, and calendar period.

OBJECTIVE:--The purpose of this study was to estimate the risks of nontraumatic lower-extremity amputations (LEAs) in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS--We identified 31,354 patients with type 1 diabetes (15,001 women and 16,353 men) in the Swedish Inpatient Register between 1975 and 2004. The incidence of nontraumatic LEAs was followed up until 31 December 2004 by cross-linkage in the Inpatient Register and linkage to the Death and Migration registers. Poisson regression modeling was used to compare the risks of nontraumatic LEAs during different calendar periods of follow-up, with adjustment for both sex and attained age at follow-up. Standardized incidence ratios (SIRs) were used to estimate the relative risks (RRs) with the age-, sex-, and calendar period-matched general Swedish population as reference. The cumulative probability of nontraumatic LEAs was calculated by the Kaplan-Meier method. RESULTS:--In total, 465 patients with type 1 diabetes underwent nontraumatic LEAs. The risk was lower during the most recent calendar period (2000-2004) than during the period before 2000 (RR 0.6 [95% CI 0.5-0.8]). However, even in this most recent period, the risk for nontraumatic LEAs among these relatively young patients was 86-fold higher than that in the matched general population (SIR 85.8 [72.9-100.3]). By age 65 years, the cumulative probability of having a nontraumatic LEA was 11.0% for women with type 1 diabetes and 20.7% for men with type 1 diabetes. CONCLUSIONS:--Although the risks appeared to have declined in recent years, patients with type 1 diabetes still have a very high risk for nontraumatic LEAs.

The population of Leningrad suffered from severe starvation, cold and psychological stress during the siege in 1941–1944. We investigated long-term effects of the siege on cardiovascular risk factors and mortality in surviving men and women. 3905 men born 1916–1935 and 1729 women born 1910–1940, resident in St Petersburg (formerly Leningrad) between 1975 and 1982, of whom a third experienced the siege as children, adolescents or young adults, were examined for cardiovascular risk factors in 1975–1977 and 1980–1982 respectively and followed till end 2005. Effects of siege exposure on blood pressure, lipids, body size, and mortality were studied in multivariate analysis stratified by gender and period of birth, adjusted for age, smoking, alcohol and social characteristics. Women who were 6–8 years-old and men who were 9–15 years-old at the peak of starvation had higher systolic blood pressure compared to unexposed subjects born during the same period of birth (fully adjusted difference 8.8, 95% CI: 0.1–17.5 mm Hg in women and 2.9, 95% CI: 0.7–5.0 mm Hg in men). Mean height of women who were exposed to siege as children appeared to be greater than that of unexposed women. Higher mortality from ischaemic heart disease and cerebrovascular disease was noted in men exposed at age 6–8 and 9–15, respectively. The experience of severe stress and starvation in childhood and puberty may have long-term effects on systolic blood pressure and circulatory disease in surviving men and women with potential gender differences in the effect of siege experienced at pre-pubertal age.