Glucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study.

OBJECTIVE: To investigate whether use of glucagon-like peptide 1 (GLP1) receptor agonists is associated with increased risk of thyroid cancer. DESIGN: Scandinavian cohort study. SETTING: Denmark, Norway, and Sweden, 2007-21. PARTICIPANTS: Patients who started GLP1 receptor agonist treatment were compared with patients who started dipeptidyl peptidase 4 (DPP4) inhibitor treatment, and in an additional analysis, patients who started sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. MAIN OUTCOME MEASURES: Thyroid cancer identified from nationwide cancer registers. An active-comparator new user study design was used to minimise risks of confounding and time related biases from using real world studies of drug effects. Cox regression was used to estimate hazard ratios, controlling for potential confounders with propensity score weighting. RESULTS: The mean follow-up time was 3.9 years (standard deviation 3.5 years) in the GLP1 receptor agonist group and 5.4 years (standard deviation 3.5 years) in the DPP4 inhibitor group. 76 of 145 410 patients (incidence rate 1.33 events per 10 000 person years) treated with GLP1 receptor agonists and 184 of 291 667 patients (incidence rate 1.46 events per 10 000 person years) treated with DPP4 inhibitors developed thyroid cancer. GLP1 receptor agonist use was not associated with increased risk of thyroid cancer (hazard ratio 0.93, 95% confidence interval 0.66 to 1.31; rate difference -0.13, 95% confidence interval -0.61 to 0.36 events per 10 000 person years). The hazard ratio for medullary thyroid cancer was 1.19 (0.37 to 3.86). In the additional analysis comparing the GLP1 receptor agonist group with the SGLT2 inhibitor group, the hazard ratio for thyroid cancer was 1.16 (0.65 to 2.05). CONCLUSIONS: In this large cohort study using nationwide data from three countries, GLP1 receptor agonist use was not associated with a substantially increased risk of thyroid cancer over a mean follow-up of 3.9 years. In the main analysis comparing GLP1 receptor agonists with DPP4 inhibitors, the upper limit of the confidence interval was consistent with no more than a 31% increase in relative risk.

Sexual Behaviors among Individuals Aged 20-49 in Japan: Initial Findings from a Quasi-Representative National Survey, 2022.

Nationally representative data on sexual health and behaviors in Japan are scarce. We conducted an online survey, including questions about a range of topics related to sexual behaviors and outcomes. The sample, including 8000 men and women aged 20-49 years in Japan, was stratified by sex and weighted with respect to age, marital status, and region of residence to reflect the population of Japan. Of the women, 82.9% and 10.0% reported that they were heterosexual and asexual, respectively; corresponding proportions for men were 87.4% and 6.9%. 15.3% of women and 19.8% of men reported never having had any partners with whom they engaged in vaginal, anal, or oral sex. 45.3% of women and 44.5% of men reported not having had any sexual partners during the past year; this proportion was highest among women aged 40-49 years (51.7%) and men aged 20-29 years (55.1%). The proportion of those reporting satisfaction with their sex life was 27.8% for women and 23.1% for men; 17.6% of women and 27.1% of men reported dissatisfaction. Pornography use of ≥3 times per week was most common among those aged 20-29 years (6.5% of women; 34.8% of men), and the frequency of pornography use decreased slightly with age. 4.0% of women and 48.3% of men reported ever having used commercial sex worker services in their lifetime. This survey-based study provides data on sexual behaviors and health outcomes in Japan. Compared to other high-income countries, levels of sexual inexperience and inactivity seem to be high in Japan.

Depression and anxiety-related disorders and suicide among Swedish male elite football players: a nationwide cohort study.

OBJECTIVE: To assess whether male elite football players, during and after their active career, were at increased risk of depression and anxiety-related disorders and suicide, as compared with the general male population. METHODS: We included male football players active in the Swedish top division 1924-2019 and general male population (matched to football players based on age and region of residence) aged <65 years in 1997. Using nationwide registers, we followed the football players from their first season in the top division (or the date of their first registered residency in Sweden) or 1 January 1997, and compared the risk of depression and anxiety-related disorders (captured through diagnoses from hospital admissions and outpatient visits, and use of prescription drugs) among football players versus controls. In a secondary analysis using data from death certificates, we compared the risk of suicide between football players and general population males who were alive in 1969 (when cause of death became available) . RESULTS: During follow-up through 31 December 2020, 504 (13.6%) of 3719 football players and 7455 (22.3%) of 33 425 general population males had a depression or anxiety-related disorder. In analyses accounting for age, region of residence and calendar time, the risk of anxiety and depression-related disorders was lower among football players versus general population males (HR 0.61, 95% CI 0.55 to 0.66). The protective association was attenuated with increasing age, and from around age 70 years the risk was similar in the two groups. The risk of suicide was lower among football players versus general population males (HR 0.48, 95% CI 0.32 to 0.72). CONCLUSIONS: In this nationwide cohort study in Sweden, elite male football players had a lower risk of depression and anxiety-related disorders and suicide as compared with the general population.

Association of glucagon-like peptide-1 receptor agonists with serious liver events among patients with type 2 diabetes: A Scandinavian cohort study.

BACKGROUND AND AIMS: Clinical trials suggest that glucagon-like peptide-1 (GLP-1) receptor agonists may have beneficial effects on NAFLD, but the impact on hard hepatic end points is unknown. We assessed the association between the use of GLP-1 receptor agonists and the risk of serious liver events in routine clinical practice. APPROACH AND RESULTS: Cohort study using data from nationwide registers in Sweden, Denmark, and Norway, 2007-2020, including 91,479 initiators of GLP-1 receptor agonists and 244,004 initiators of the active comparator, dipeptidyl peptidase-4 inhibitors, without a history of chronic liver disease other than NAFLD/NASH. The primary outcome was serious liver events: a composite of incident compensated and decompensated cirrhosis and HCC. Secondary outcomes were the individual components of the primary outcome. Cox regression was used to estimate HRs, using propensity score weighting to control for confounding. Users of GLP-1 receptor agonists had 608 serious liver events (adjusted incidence rate: 16.9 events per 10,000 person-years), compared with 1770 events among users of dipeptidyl peptidase-4 inhibitors (19.2 events per 10,000 person-years). The adjusted HR was 0.85 (95% CI: 0.75 to 0.97), and the rate difference was -2.1 (-4.4 to 0.1) events per 10,000 person-years. In secondary outcome analyses, the adjusted HR was 0.85 (0.75 to 0.97) for compensated and decompensated cirrhosis and 1.05 (0.80 to 1.39) for HCC. CONCLUSIONS: The use of GLP-1 receptor agonists was associated with a significantly reduced risk of serious liver events, driven by a reduction of compensated and decompensated cirrhosis.

Use of DPP4 Inhibitors and GLP-1 Receptor Agonists and Risk of Intestinal Obstruction: Scandinavian Cohort Study.

BACKGROUND & AIMS: Concerns have been raised that the incretin-based diabetes drugs dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists may increase the risk of intestinal obstruction. We aimed to assess the association between use of DPP4 inhibitors and GLP-1 receptor agonists and the risk of intestinal obstruction. METHODS: Using data from nationwide registers in Sweden, Denmark, and Norway, 2013-2021, we conducted 2 cohort studies, one for DPP4 inhibitors and one for GLP-1 receptor agonists, to investigate the risk of intestinal obstruction as compared with an active comparator drug class (sodium-glucose co-transporter 2 [SGLT2] inhibitors). RESULTS: Among 19,0321 new users of DPP4 inhibitors (median (interquartile range [IQR]) follow-up time, 1.3 [0.6-2.6] years) and 139,315 new users of SGLT2 inhibitors (median [IQR] follow-up time, 0.8 [0.4-1.7] years), 919 intestinal obstruction events occurred. Use of DPP4 inhibitors, as compared with SGLT2 inhibitors, was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate, 2.0 vs 1.8 per 1000 person-years; hazard ratio, 1.13; 95% confidence interval, 0.96-1.34). Among 121,254 new users of GLP-1 receptor agonists (median [standard deviation] follow-up time, 0.9 [0.4-1.9] years) and 185,027 new users of SGLT2 inhibitors (median [IQR] follow-up time, 0.8 [0.4-1.8] years), 557 intestinal obstruction events occurred. Use of GLP-1 receptor agonists was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate, 1.3 vs 1.6 per 1000 person-years; hazard ratio, 0.83; 95% confidence interval, 0.69-1.01). CONCLUSIONS: In this analysis of nationwide data from 3 countries, previous safety signals indicating an increased risk of intestinal obstruction with use of DPP4 inhibitors and GLP-1 receptor agonists were not confirmed.

Elevated low-density lipoprotein cholesterol: An inverse marker of morbidity and mortality in patients with myocardial infarction.

BACKGROUND: The incidence of atherosclerotic cardiovascular disease increases with levels of low-density lipoprotein cholesterol (LDL-C). Yet, a paradox may exist where lower LDL-C levels at myocardial infarction (MI) are associated with poorer prognoses. OBJECTIVE: To assess the association between LDL-C levels at MI with risk factor burden and cause-specific outcomes. METHODS: Statin-naive patients hospitalized for a first MI and registered in SWEDEHEART were included. Data were linked to Swedish registers. Primary outcomes were all-cause mortality and nonfatal MI. Associations between LDL-C and outcomes were assessed using adjusted proportional hazards models. RESULTS: Among 63,168 patients (median age, 66 years), the median LDL-C level was 3.0 mmol/L (interquartile range 2.4-3.6). Patient age and comorbidities increased as LDL-C decreased. During a median follow-up of 4.5 years, 10,236 patients died, and 4973 had nonfatal MI. Patients with the highest LDL-C had a lower risk of mortality (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.71-0.80). The risk of hospitalization for pneumonia, hip fracture, chronic obstructive pulmonary disease, and new cancer diagnosis was lower with higher LDL-C (HR range, 0.40-0.81). Patients with the highest LDL-C had a greater risk of recurrent MI (HR 1.16; 95% CI 1.07-1.26). CONCLUSIONS: Patients with the highest LDL-C levels at MI had the lowest incidence of mortality and morbidity. This seems to reflect lower age at MI, less underlying morbidities, paired with the modifiability of LDL-C. However, supporting the causal association between LDL-C and ischemic heart disease, elevated LDL-C was simultaneously associated with an increased risk of nonfatal MI.

Neurodegenerative disease among male elite football (soccer) players in Sweden: a cohort study.

BACKGROUND: Football (soccer) players might be at increased risk of neurodegenerative disease, which has led to questions regarding the safety of the sport and recent measures introduced by football associations to reduce heading of the ball. We aimed to assess the risk of neurodegenerative disease among male football players in the Swedish top division Allsvenskan, compared with matched controls. METHODS: In this cohort study, we identified all male football players (amateurs and professionals) who had played at least one game in Allsvenskan from Aug 1, 1924 to Dec 31, 2019 and excluded players whose personal identity number could not be retrieved or be identified in the Total Population Register, and those who were not born in Sweden and who had immigrated to the country after age 15 years. Football players were matched with up to ten controls from the general population according to sex, age, and region of residence. We used nationwide registers to compare the risk of neurodegenerative disease (diagnoses recorded in death certificates, during hospital admissions and outpatient visits, or use of prescription drugs for dementia) among football players versus controls. We also assessed each type of neurodegenerative disease (Alzheimer's disease and other dementias, motor neuron disease, and Parkinson's disease) separately, and compared the risk of neurodegenerative disease among outfield players versus goalkeepers. FINDINGS: Of 7386 football players who had played at least one game in the top Swedish division between Aug 1, 1924, and Dec 31, 2019, 182 players were excluded for an unretrievable personal identity number, and 417 were excluded due to their number not being identified in the Total Population Register. After a further exclusion of 780 players and 11 627 controls who were born outside of Sweden and who had immigrated to the country after age 15 years, 6007 football players (510 goalkeepers) were included in the study population along with 56 168 matched controls. During follow-up to Dec 31, 2020, 537 (8·9%) of 6007 football players and 3485 (6·2%) of 56 168 controls were diagnosed with neurodegenerative disease. The risk of neurodegenerative disease was higher among football players than controls (hazard ratio [HR] 1·46 [95% CI 1·33-1·60]). Alzheimer's disease and other dementias were more common among football players than controls (HR 1·62 [95% CI 1·47-1·78]), significant group differences were not observed for motor neuron disease (HR 1·27 [0·73-2·22]), and Parkinson's disease was less common among football players (HR 0·68 [0·52-0·89]). The risk of neurodegenerative disease was higher for outfield players than controls (HR 1·50 [95% CI 1·36-1·65]) but not for goalkeepers versus controls (HR 1·07 [0·78-1·47]), and outfield players had a higher risk of neurodegenerative disease than did goalkeepers (HR 1·43 [1·03-1·99]). All-cause mortality was slightly lower among football players than controls (HR 0·95 [95% CI 0·91-0·99]). INTERPRETATION: In this cohort study, male football players who had played in the Swedish top division had a significantly increased risk of neurodegenerative disease compared with population controls. The risk increase was observed for Alzheimer's disease and other dementias but not for other types of neurodegenerative disease, and among outfield players, but not among goalkeepers. Our study expands on the data that can be used to assess and manage risks in the sport. FUNDING: Karolinska Institutet, The Swedish Research Council for Sport Science, Folksam Research Foundation, Hedberg Foundation, Neurofonden, and Åhlen Foundation.

Inhaled ciclesonide in adults hospitalised with COVID-19: a randomised controlled open-label trial (HALT COVID-19).

OBJECTIVE: To assess the efficacy of inhaled ciclesonide in reducing the duration of oxygen therapy (an indicator of time to clinical improvement) among adults hospitalised with COVID-19. DESIGN: Multicentre, randomised, controlled, open-label trial. SETTING: 9 hospitals (3 academic hospitals and 6 non-academic hospitals) in Sweden between 1 June 2020 and 17 May 2021. PARTICIPANTS: Adults hospitalised with COVID-19 and receiving oxygen therapy. INTERVENTION: Inhaled ciclesonide 320 µg two times a day for 14 days versus standard care. MAIN OUTCOME MEASURES: Primary outcome was duration of oxygen therapy, an indicator of time to clinical improvement. Key secondary outcome was a composite of invasive mechanical ventilation/death. RESULTS: Data from 98 participants were analysed (48 receiving ciclesonide and 50 receiving standard care; median (IQR) age, 59.5 (49-67) years; 67 (68%) men). Median (IQR) duration of oxygen therapy was 5.5 (3-9) days in the ciclesonide group and 4 (2-7) days in the standard care group (HR for termination of oxygen therapy 0.73 (95% CI 0.47 to 1.11), with the upper 95% CI being compatible with a 10% relative reduction in oxygen therapy duration, corresponding to a <1 day absolute reduction in a post-hoc calculation). Three participants in each group died/received invasive mechanical ventilation (HR 0.90 (95% CI 0.15 to 5.32)). The trial was discontinued early due to slow enrolment. CONCLUSIONS: In patients hospitalised with COVID-19 receiving oxygen therapy, this trial ruled out, with 0.95 confidence, a treatment effect of ciclesonide corresponding to more than a 1 day reduction in duration of oxygen therapy. Ciclesonide is unlikely to improve this outcome meaningfully. TRIAL REGISTRATION NUMBER: NCT04381364.

Sodium-Glucose Cotransporter 2 Inhibitor Treatment and Risk of Atrial Fibrillation: Scandinavian Cohort Study.

OBJECTIVE: To assess the association between use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and the risk of new-onset atrial fibrillation (AF) in routine clinical practice. RESEARCH DESIGN AND METHODS: We used nationwide registers in Denmark, Norway, and Sweden from 2013 to 2018 in order to include patients without a history of AF who were newly prescribed an SGLT2 inhibitor or an active comparator (glucagon-like peptide 1 [GLP-1] receptor agonist). We performed a cohort study to assess new-onset AF in intention-to-treat analyses using Cox regression, adjusted for baseline covariates with propensity score weighting. RESULTS: We identified 79,343 new users of SGLT2 inhibitors (59.2% dapagliflozin, 40.0% empagliflozin, 0.8% canagliflozin, <0.1% ertugliflozin) and 57,613 new users of GLP-1 receptor agonists. Mean age of the study cohort was 61 years and 60% were men. The adjusted incidence rate of new-onset AF was 8.6 per 1,000 person-years for new users of SGLT2 inhibitors compared with 10.0 per 1,000 person-years for new users of GLP-1 receptor agonists. The adjusted hazard ratio (aHR) was 0.89 (95% CI 0.81-0.96), and the rate difference was 1.4 fewer events per 1,000 person-years (95% CI 0.6-2.1). Using an as-treated exposure definition, the aHR for new-onset AF was 0.87 (95% CI 0.76-0.99). No statistically significant heterogeneity of the aHRs was observed between subgroups of patients with and without a history of heart failure or major cardiovascular disease. CONCLUSIONS: In this cohort study using nationwide data from three countries, use of SGLT2 inhibitors, compared with GLP-1 receptor agonists, was associated with a modestly reduced risk of new-onset AF.

Understanding the sex inequality in childlessness: an approach using Swedish register data.

In most countries, men are more likely to be childless than women. Understanding how this inequality arises is important given the significance of parenthood for individuals' lives. The objective of this study was to explore how three prominent explanations for sex inequalities in childlessness relate to the Sex Gap in Childlessness (SGC) in Sweden. The three explanations examined were sex ratio imbalance (more men than women), mismeasurement of fatherhood (inequalities in registration) and partnership differences (inequality in multi-partner fertility). Administrative register data for cohorts born in 1945-1974 were used. The population was restricted to men and women who were born in Sweden or arrived prior to the age of 15, and all registered childbearing partnerships were examined. To explore the possible significance of the three explanations, counter-factual standardization was used. Of the three explanations examined, the population sex ratio had the largest positive impact on the SGC, while multi-partner fertility had a negative impact. The results show that inequalities in the sex ratio can explain about 20-34% of the SGC depending on cohort. Inequalities in registration of fathers explain about 9-24% of the SGC depending on cohort. Finally, results show that women are slightly more likely to have multiple partners, and that this behaviour has a substantial minimizing effect on the SGC (minimizing it by 6-65%). To the authors' knowledge this was the first paper to estimate the scope of the impacts of these three mechanisms on the SGC. Differences in multi-partner fertility have in many instances been used as an explanation for men's higher childlessness. This study shows that women have slightly more childbearing partners than men, and that this actually leads to a smaller SGC in the studied population.

Use of sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists according to the 2019 ESC guidelines and the 2019 ADA/EASD consensus report in a national population of patients with type 2 diabetes.

AIMS: To assess treatment eligibility for, and received treatment with, sodium-glucose co-transporter 2 inhibitors (SGLT2) and glucagon-like peptide-1 (GLP-1) receptor agonists according to the 2019 the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus report and the 2019 European Society of Cardiology (ESC) guidelines in a nationwide sample of patients with type 2 diabetes. METHODS AND RESULTS: Both sets of guidelines included the treatment indications of heart failure, chronic kidney disease, and atherosclerotic cardiovascular disease while only the 2019 ESC guidelines also recommended treatment based on high or very high cardiovascular risk. The analyses included 435 000 patients with type 2 diabetes identified from the Swedish National Diabetes Register (2020-21). According to the 2019 ESC guidelines, 79.5% were recommended any of the two drugs (SGLT2 inhibitors: 37.2%; SGLT2 inhibitors or GLP-1 receptor agonists: 40.9%; GLP-1 receptor agonists: 1.4%). According to the 2019 ADA/EASD consensus report, 48.8% were recommended any of the two drugs (SGLT2 inhibitors: 37.2%; GLP-1 receptor agonists: 11.6%). Of those who had been recommended any of the two drugs, 33.7% had received the recommended treatment according to the 2019 ESC guidelines and 25.4% according to the 2019 ADA/EASD consensus report. CONCLUSIONS: In this nationwide study, the proportion of patients with type 2 diabetes who were recommended treatment with an SGLT2 inhibitor or a GLP-1 receptor agonist was approximately 80% according to the 2019 ESC guidelines and around half according to the 2019 ADA/EASD consensus report. Uptake of these recommendations in routine clinical practice was limited.

We investigated the proportion of patients with type 2 diabetes in Sweden who were recommended treatment with two types of diabetes drugs, SGLT2 inhibitors, and GLP-1 receptor agonists, according to two European clinical guidelines. • Depending on the guideline used, between half and 80% of the patients with type 2 diabetes were recommended treatment with an SGLT2 inhibitor or a GLP-1 receptor. • Of those who had been recommended any of the two drugs, one in three or one in four, depending on the guideline used, had received the recommended treatment.

Lipid Lowering in "Very High Risk" Patients Undergoing Coronary Artery Bypass Surgery and Its Projected Reduction in Risk for Recurrent Vascular Events: A Monte Carlo Stepwise Simulation Approach.

ABSTRACT: 2018 AHA guidelines provide criteria to identify patients at very high risk (VHR) for adverse vascular events and recommend an low density lipoprotein-C (LDL-C) level <1.8 mmol/L. Data regarding the 10-year risk for adverse vascular events in coronary artery bypass grafting (CABG) patients at VHR and the need for nonstatin therapies in the VHR cohort are limited. We queried a national cohort of CABG patients to answer these questions. The projected reduction of LDL-C from stepwise escalation of lipid-lowering therapy (LLT) was simulated; Monte Carlo methods were used to account for patient-level heterogeneity in treatment effects. Data on preoperative statin therapy and LDL-C levels were obtained. In the first scenario, all eligible patients not at target LDL-C received high-intensity statins, followed by ezetimibe and then alirocumab; alternatively, bempedoic acid was also used. The 10-year risk for an adverse vascular event was estimated using a validated risk score. Potential risk reduction was estimated after simulating maximal LLT. Before CABG, 8948 of 27,443 patients (median LDL-C 85 mg/dL) were at VHR. In the whole cohort, 31% were receiving high-intensity statins. With stepwise LLT escalation, the proportion of patients at target were 60%, 78%, 86%, and 97% after high-intensity statins, ezetimibe, bempedoic acid, and alirocumab, respectively. The projected 10-year risk to suffer a vascular event reduced by 4.6%. A large proportion of CABG patients who are at VHR for vascular events fail to meet 2018 AHA LDL-C targets. A stepwise approach, particularly with the use of bempedoic acid, can significantly reduce the need for more expensive proprotein convertase subtilisin kexin 9 inhibitors.

Recent changes in the reporting of STIs in Japan during the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic has had variable effects on the rates of STIs reported across the globe. This study sought to assess how the number of STI reports changed during the pandemic in Japan. METHODS: We used national infectious disease surveillance data from the National Institute of Infectious Diseases (Tokyo, Japan) for the period between January 2013 and December 2021. We compared reported rates of chlamydia, gonorrhoea, condyloma acuminata and genital herpes, as well as total notifications for HIV/AIDS and syphilis during the pandemic versus previous years in Japan. We used a quasi-Poisson regression to determine whether any given week or month between January 2018 and December 2021 had a significant excess or deficit of STIs. Notification values above or below the 95% upper and lower prediction thresholds were considered as statistically significant. The start of the pandemic was defined as January 2020. RESULTS: Chlamydia generally remained within predicted range during the pandemic period. Reporting of gonorrhoea was significantly higher than expected throughout early-to-mid 2021 but otherwise generally remained within predicted range prior to 2021. Condyloma, herpes and HIV/AIDS reporting were transiently significantly lower than expected throughout the pandemic period, but no significant periods of higher-than-expected reporting were detected. Syphilis showed widespread evidence of significantly lower-than-predicted reporting throughout 2020 but eventually reversed, showing significantly higher-than-predicted reporting in mid-to-late 2021. CONCLUSIONS: The COVID-19 pandemic was associated with variable changes in the reporting of STIs in Japan. Higher-than-predicted reporting was more likely to be observed in the later phases of the pandemic. These changes may have been attributable to pandemic-related changes in sexual behaviour and decreased STI clinic attendance and testing, but further research on the long-term impact of the pandemic on STIs is necessary.

Alcohol related disorders among elite male football players in Sweden: nationwide cohort study.

OBJECTIVES: To assess whether male elite football players are at increased risk of alcohol related disorders compared with men from the general population, and whether such an increased risk would vary on the basis of calendar year of the first playing season in the top tier of competition, age, career length, and goal scoring abilities. DESIGN: Nationwide cohort study. SETTING: Sweden, 1924-2020. PARTICIPANTS: 6007 male football players who had played in the Swedish top division, Allsvenskan, from 1924 to 2019 and 56 168 men from the general population matched to players based on age and region of residence. MAIN OUTCOME MEASURES: Primary outcome was alcohol related disorders (diagnoses recorded in death certificates, during hospital admissions and outpatient visits, or use of prescription drugs for alcohol addiction); secondary outcome was disorders related to misuse of other drugs. RESULTS: During follow-up up to 31 December 2020, 257 (4.3%) football players and 3528 (6.3%) men from the general population received diagnoses of alcohol related disorders. In analyses accounting for age, region of residence, and calendar time, risk of alcohol related disorders was lower among football players than among men from the general population (hazard ratio 0.71, 95% confidence interval 0.62 to 0.81). A reduced risk of alcohol related disorders was observed for football players who played their first season in the top tier in the early 1960s and later, while no significant difference versus men from the general population was seen in the risk for football players from earlier eras. The hazard ratio was lowest at around age 35 years, and then increased with age; at around age 75 years, football players had a higher risk of alcohol related disorders than men from the general population. No significant association was seen between goal scoring, number of games, and seasons played in the top tier and the risk of alcohol related disorders. Risk of disorders related to other drug misuse was significantly lower among football players than the general population (hazard ratio 0.22, 95% confidence interval 0.15 to 0.34). CONCLUSIONS: In this nationwide cohort study, male football players who had played in the Swedish top tier of competition had a significantly lower risk of alcohol related disorders than men from the general population.

Association of Ischemic and Bleeding Events With Mortality Among Patients in Sweden With Recent Acute Myocardial Infarction Receiving Antithrombotic Therapy.

Importance: Antithrombotic treatment after myocardial infarction (MI) should be individualized based on the patient's risk of ischemic and bleeding events. Uncertainty remains regarding the relative prognostic importance of the 2 types of events, and further study would be useful. Objectives: To compare the association of ischemic vs bleeding events with mortality in patients with a recent MI and assess whether the relative mortality risk for the 2 types of events has changed over the past 2 decades. Design, Setting, and Participants: A cohort study based on nationwide registers in Sweden, 2012-2017, was conducted. Data were analyzed between July 2021 and May 2022. Patients with MI who were discharged alive with antithrombotic therapy (antiplatelet therapy or oral anticoagulation) were included in the analysis. Main Outcomes and Measures: The incidence of a first ischemic event (hospitalization for MI or ischemic stroke) or bleeding event (hospitalization with bleeding) up to 1 year after discharge and the mortality risk up to 1 year after each type of event were assessed. Cox proportional hazards regression models were used to estimate adjusted hazard ratios (aHRs) for 1-year mortality after an ischemic and bleeding event vs no event, and after an ischemic vs bleeding event. Adjusted HRs for mortality after ischemic vs bleeding events were compared among patients discharged in 1997-2000, 2001-2011, and 2012-2017. Results: Of 86 736 patients discharged after MI in 2012-2017 (median age, 71 [IQR, 62-80] years; 57 287 [66.0%] men), 4039 individuals experienced a first ischemic event (5.7 per 100 person-years) and 3399 experienced a first bleeding event (4.8 per 100 person-years). The mortality rate was 46.2 per 100 person-years after an ischemic event and 27.1 per 100 person-years after a bleeding event. The aHR for 1-year mortality vs no event was 4.16 (95% CI, 3.91-4.43) after an ischemic event and 3.43 (95% CI, 3.17-3.71) after a bleeding event. When the 2 types of events were compared, the aHR was 1.27 (95% CI, 1.15-1.40) for an ischemic vs bleeding event. There was no statistically significant difference in the aHR of an ischemic vs bleeding event in 1997-2000, 2001-2011, and 2012-2017. Conclusions and Relevance: In this nationwide cohort study of patients with a recent MI, postdischarge ischemic events were more common and associated with higher mortality risk compared with bleeding events.

Assessment of Traffic Accidents in Japan during the COVID-19 Pandemic vs. Previous Years: A Preliminary Report.

Beginning in April 2020, social distancing measures were implemented to mitigate the COVID-19 pandemic in Japan. We assessed whether traffic accident rates had decreased from April 2020 to December 2021 as compared with previous years. The analysis included 2,934,477 traffic accidents, and the trend of decreasing rates of traffic accidents in recent years and seasonal fluctuations in traffic accidents were considered. The yearly change in the traffic accident rate between 2015 and 2019 was estimated, and the traffic accident rate in 2020 and 2021 was predicted. This was followed by the comparison of observed vs. predicted traffic accident rate. In 2020, the observed vs. expected rates of traffic accidents were lower in April to December 2020, and the rate of traffic accidents in Japan was 30-40% lower in April-May 2020 than would be expected based on trends from previous years. In 2021, rates of traffic accidents remained lower than expected between January and November, but the magnitude of decrease was not as pronounced. These findings could be explained by social distancing policies, including the declaration of the state of emergency, and the relaxation of public health and social measures over time.

Changes in marriage, divorce and births during the COVID-19 pandemic in Japan.

INTRODUCTION: Marriage, divorce and fertility are declining in Japan. There is concern that the COVID-19 pandemic may have accelerated the decrease in marriages and births while increasing the number of divorces. Changes in partnership behaviours and fertility have significant implications for mental health, well-being and population demographics. METHODS: Japanese vital statistical data were collected for December 2011-May 2021. We used the Farrington algorithm on the daily numbers of marriages, divorces and births (per month) in order to determine whether any given month between January 2017 and May 2021 had a significant excess or deficit. Analyses were conducted at the national and regional levels. RESULTS: During the pandemic, significant deficits in the national number of marriages were noted in January 2020, April 2020, May 2020, July 2020, September 2020 and April 2021. Regional marriage patterns reflected national trends. Divorces were noted to be in deficit during April 2020, May 2020 and May 2021 at the country level. Regional analyses mirrored national divorce trends with the exception of Shikoku, which showed no deficits during the pandemic. Significant deficits in the number of total births were noted in December 2020, January 2021 and February 2021. Regionally, birth deficits were concentrated in Chubu, Kansai and Kanto. After the start of the pandemic, no significant excesses in marriages, divorces or births were noted at the national or regional level. CONCLUSIONS: Marriages and divorces declined during the pandemic in Japan, especially during state of emergency declarations. There were decreased births between December 2020 and February 2021, approximately 8-10 months after the first state of emergency, suggesting that couples altered their pregnancy intention in response to the pandemic. Metropolitan regions were more affected by the pandemic than their less metropolitan counterparts.

Salaries, degrees, and babies: Trends in fertility by income and education among Japanese men and women born 1943-1975-Analysis of national surveys.

BACKGROUND: While fertility rates have decreased during the second half of the 20th century in Japan, little is known regarding trends in the number of children that men and women have across birth cohorts and whether these differ by education and income. METHODS: We used data from four rounds of the National Fertility Survey (1992, 2005, 2010 and 2015) and included men and women aged 40-49 years (16728 men and 17628 women). By 5-year birth cohorts, we assessed the distribution of number of children (0, 1, 2 and 3 or more) and total fertility (the mean number of children) at completed fertility (age 45-49 or 40-44 years depending on birth cohort). We assessed trends in these fertility outcomes in men and women separately, and by education (no university education; university education) for men and women and by reported annual income (0 to <3 000 000 JPY; 3 000 000 to <6 000 000 JPY; ≥6 000 000 JPY) for men. RESULTS: When comparing those born in 1943-1948 with those born in 1971-1975, the proportion with no children had increased from 14.3 to 39.9% for men and from 11.6 to 27.6% for women. This increase coincided with a decrease in the proportions of individuals with 2 or more children. Total fertility had decreased from 1.92 to 1.17 among men and from 1.96 to 1.42 among women. For men, those with a university degree were more likely to have children than those without a university degree in all birth cohorts except 1943-1947. Men with higher income were more likely to have children across birth cohorts. While the proportion who had children had decreased in all income groups, the decrease was steeper among those in the lowest income group. Among women born 1956-1970, those with a university degree were less likely to have children than those without a university degree; this difference was no longer seen among those born 1971-1975. For both men and women, trends in having children and total fertility across birth cohorts did not differ by educational status. CONCLUSIONS: The decline in the total fertility rate in Japan can be attributed to both an increasing proportion of the population who have no children and a lower number of children among those who have children. Men with lower education and income were less likely to have children and the disparity in the number of children that men have by income had increased in more recent birth cohorts. Among women, higher education was associated with lower fertility, although this pattern was no longer observed among those born in 1971-1975.