She teaches epidemiology in MSc and PhD courses at the School of Medical Sciences, Örebro University.

I urval från Stockholms universitets publikationsdatabas

• COVID-19 case-fatality rate and demographic and socioeconomic influencers

  2020. Yang Cao, Ayako Hiyoshi, Scott Montgomery. BMJ Open 10 (11)

  Artikel

  Objective To investigate the influence of demographic and socioeconomic factors on the COVID-19 case-fatality rate (CFR) globally.

  Design Publicly available register-based ecological study.

  Setting Two hundred and nine countries/territories in the world.

  Participants Aggregated data including 10 445 656 confirmed COVID-19 cases.

  Primary and secondary outcome measures COVID-19 CFR and crude cause-specific death rate were calculated using country-level data from the Our World in Data website.

  Results The average of country/territory-specific COVID-19 CFR is about 2%–3% worldwide and higher than previously reported at 0.7%–1.3%. A doubling in size of a population is associated with a 0.48% (95% CI 0.25% to 0.70%) increase in COVID-19 CFR, and a doubling in the proportion of female smokers is associated with a 0.55% (95% CI 0.09% to 1.02%) increase in COVID-19 CFR. The open testing policies are associated with a 2.23% (95% CI 0.21% to 4.25%) decrease in CFR. The strictness of anti-COVID-19 measures was not statistically significantly associated with CFR overall, but the higher Stringency Index was associated with higher CFR in higher-income countries with active testing policies (regression coefficient beta=0.14, 95% CI 0.01 to 0.27). Inverse associations were found between cardiovascular disease death rate and diabetes prevalence and CFR.

  Conclusion The association between population size and COVID-19 CFR may imply the healthcare strain and lower treatment efficiency in countries with large populations. The observed association between smoking in women and COVID-19 CFR might be due to the finding that the proportion of female smokers reflected broadly the income level of a country. When testing is warranted and healthcare resources are sufficient, strict quarantine and/or lockdown measures might result in excess deaths in underprivileged populations. Spatial dependence and temporal trends in the data should be taken into account in global joint strategy and/or policy making against the COVID-19 pandemic.

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• Comorbid disease burden among MS patients 1968-2012

  2021. Kelsi A. Smith (et al.). Multiple Sclerosis Journal 27 (2), 268-280

  Artikel

  Background: People with multiple sclerosis (pwMS) have increased comorbid disease (CMD) risk. Most previous studies have not considered overall CMD burden. Objective: To describe lifetime CMD burden among pwMS. Methods: PwMS identified using Swedish registers between 1968 and 2012 (n = 25,476) were matched by sex, age, and county of residence with general-population comparators (n = 251,170). Prevalence, prevalence ratios (PRs), survival functions, and hazard ratios by MS status, age, and time period compared seven CMD: autoimmune, cardiovascular, depression, diabetes, respiratory, renal, and seizures. Results: The magnitude of the PRs for each CMD and age group decreased across time, with higher PRs in earlier time periods. Before 1990, younger age groups had higher PRs, and after 1990, older age groups had higher PRs. Male pwMS had higher burden compared with females. Overall, renal, respiratory, and seizures had the highest PRs. Before 2001, 50% of pwMS received a first/additional CMD diagnosis 20 years prior to people without MS, which reduced to 4 years after 2001. PwMS had four times higher rates of first/additional diagnoses in earlier time periods, which reduced to less than two times higher in recent time periods compared to people without MS. Conclusion: Swedish pwMS have increased CMD burden compared with the general population, but this has reduced over time.

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• Parental death in childhood and pathways to increased mortality across the life course in Stockholm, Sweden

  2021. Ayako Hiyoshi (et al.). PLoS Medicine 18 (3)

  Artikel

  Background

  Previous studies have shown that the experience of parental death during childhood is associated with increased mortality risk. However, few studies have examined potential pathways that may explain these findings. The aim of this study is to examine whether familial and behavioural factors during adolescence and socioeconomic disadvantages in early adulthood mediate the association between loss of a parent at age 0 to 12 and all-cause mortality by the age of 63.

  Methods and findings

  A cohort study was conducted using data from the Stockholm Birth Cohort Multigenerational Study for 12,615 children born in 1953, with information covering 1953 to 2016. Familial and behavioural factors at age 13 to 19 included psychiatric and alcohol problems in the surviving parent, receipt of social assistance, and delinquent behaviour in the offspring. Socioeconomic disadvantage in early adulthood included educational attainment, occupational social class, and income at age 27 to 37. We used Cox proportional hazard regression models, combined with a multimediator analysis, to separate direct and indirect effects of parental death on all-cause mortality.

  Among the 12,582 offspring in the study (men 51%; women 49%), about 3% experienced the death of a parent in childhood. During follow-up from the age of 38 to 63, there were 935 deaths among offspring. Parental death was associated with an elevated risk of mortality after adjusting for demographic and household socioeconomic characteristics at birth (hazard ratio [HR]: 1.52 [95% confidence interval: 1.10 to 2.08, p-value = 0.010]). Delinquent behaviour in adolescence and income during early adulthood were the most influential mediators, and the indirect associations through these variables were HR 1.03 (1.00 to 1.06, 0.029) and HR 1.04 (1.01 to 1.07, 0.029), respectively. After accounting for these indirect paths, the direct path was attenuated to HR 1.35 (0.98 to 1.85, 0.066). The limitations of the study include that the associations may be partly due to genetic, social, and behavioural residual confounding, that statistical power was low in some of the subgroup analyses, and that there might be other relevant paths that were not investigated in the present study.

  Conclusions

  Our findings from this cohort study suggest that childhood parental death is associated with increased mortality and that the association was mediated through a chain of disadvantages over the life course including delinquency in adolescence and lower income during early adulthood. Professionals working with bereaved children should take the higher mortality risk in bereaved offspring into account and consider its lifelong consequences. When planning and providing support to bereaved children, it may be particularly important to be aware of their increased susceptibility to delinquency and socioeconomic vulnerability that eventually lead to higher mortality.

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• Low health literacy and multiple medications in community-dwelling older adults

  2022. Jacques Shebehe (et al.). BMJ Open 12 (2)

  Artikel

  Objectives Adequate health literacy is important for patients to manage chronic diseases and medications. We examined the association between health literacy and multiple medications in community-dwelling adults aged 50 years and older in England.

  Design, settings and participants We included 6368 community-dwelling people of median age 66 years from the English Longitudinal Study of Ageing. Health literacy was assessed at wave 5 (2010/11) with 4 questions concerning a medication label. Four correct answers were categorised as adequate health literacy, otherwise low. Data on medications were collected at wave 6 (2012/13). To examine the difference in the number of medications between low and adequate health literacy, we used zero-inflated negative binomial regression, estimating odds ratio (OR) for zero medication and incidence rate ratios (IRR) for the number of medications, with 95% CIs. Associations were adjusted for demographic, socioeconomic and health characteristics, smoking and cognitive function. We also stratified the analysis by sex, and age (50–64 and ≥65 years). To be comparable with preceding studies, multinomial regression was fitted using commonly used thresholds of polypharmacy (0 vs 1–4, 5–9, ≥10 medications).

  Results Although low health literacy was associated with a lower likelihood of being medication-free (OR=0.64, 95% CI: 0.45 to 0.91), health literacy was not associated with the number of medications among those at risk for medication (IRR=1.01, 95% CI: 0.96 to 1.05), and this finding did not differ among younger and older age groups or women. Among men, low health literacy showed a weak association (IRR=1.06, 95% CI: 0.99 to 1.14). Multinomial regression models showed graded risks of polypharmacy for low health literacy.

  Conclusions Although there was no overall association between health literacy and the number of medications, this study does not support the assertion that low health literacy is associated with a notably higher number of medications in men.

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

  2022. Ayako Hiyoshi (et al.). Epidemiology 33 (2), 246-253

  Artikel

  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.

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• Association of Infectious Mononucleosis in Childhood and Adolescence With Risk for a Subsequent Multiple Sclerosis Diagnosis Among Siblings

  2021. Yin Xu (et al.). JAMA Network Open 4 (10)

  Artikel

  IMPORTANCE Epstein-Barr virus and its acute manifestation, infectious mononucleosis (IM), are associated with an increased risk of multiple sclerosis (MS). Whether this association is confounded by susceptibility to infection is still debated.

  OBJECTIVE To assess whether hospital-diagnosed IM during childhood, adolescence, or young adulthood is associated with subsequent MS diagnosis independent of shared familial factors.

  DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study used the Swedish Total Population Register to identify individuals born in Sweden from January 1, 1958, to December 31, 1994. Participants aged 20 years were followed up from January 1, 1978, to December 31, 2018, with a median follow-up of 15.38 (IQR, 8.68-23.55; range, 0.01-40.96) years. Data were analyzed from October 2020 to July 2021.

  EXPOSURE Hospital-diagnosed IM before 25 years of age.

  MAIN OUTCOMES AND MEASURES Diagnoses of MS from 20 years of age were identified. Risk of an MS diagnosis associated with IM in childhood (birth to 10 years of age), adolescence (11-19 years of age), and early adulthood (20-24 years of age [time-dependent variable]) were estimated using conventional and stratified (to address familial environmental or genetic confounding) Cox proportional hazards regression.

  RESULTS Of the 2 492 980 individuals (1 312 119 men [52.63%] and 1 180 861 women [47.37%]) included, 5867 (0.24%) had an MS diagnosis from 20 years of age (median age, 31.50 [IQR, 26.78-37.54] years). Infectious mononucleosis in childhood (hazard ratio [HR], 1.98; 95% CI, 1.21-3.23) and adolescence (HR, 3.00; 95% CI, 2.48-3.63) was associated with an increased risk of an MS diagnosis that remained significant after controlling for shared familial factors in stratified Cox proportional hazards regression (HRs, 2.87 [95% CI, 1.44-5.74] and 3.19 [95% CI, 2.29-4.46], respectively). Infectious mononucleosis in early adulthood was also associated with risk of a subsequent MS diagnosis (HR, 1.89; 95% CI, 1.18-3.05), but this risk was attenuated and was not significant after controlling for shared familial factors (HR, 1.51; 95% CI, 0.82-2.76).

  CONCLUSIONS AND RELEVANCE These findings suggest that IM in childhood and particularly adolescence is a risk factor associated with a diagnosis of MS, independent of shared familial factors.

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• Historical Overview of Japanese Society, Health, and Health Inequalities from the Nineteenth to the Twenty- first Century

  2020. Ayako Hiyoshi, Naoki Kondo. Health in Japan, 147-161

  Kapitel

  In the previous century, Japan rose from poverty and destruction. High levels of social inequalities before World War II were greatly equalized in the 1960–1980 period. Population health, indicated by life expectancy, height, mortality, and self-rated health, improved. Health inequalities were reduced in line with these improvements. In the past 30 years Japan has experienced low economic growth, rapid ageing, and resource constraints, with some widening of income inequalities. All are indicators of a challenging population health situation. However, health inequalities narrowed for a period in the 1990s and the early 2000s. Limited evidence suggests health inequalities have widened in recent years. Narrowing health inequality after 1990 was partly the result of worsening health in high socioeconomic groups. In the past, the combination of social structure, economic growth, culture, and social policies resulted in remarkable health development and limited health inequalities. Increased research and monitoring is needed to understand these trends, and to support policy development to reduce health inequalities as Japan changes.

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• Maternal smoking during pregnancy and fractures in offspring

  2020. Judith S. Brand (et al.). BMJ. British Medical Journal 368

  Artikel

  OBJECTIVE To study the impact of maternal smoking during pregnancy on fractures in offspring during different developmental stages of life. DESIGN National register based birth cohort study with a sibling comparison design. SETTING Sweden. PARTICIPANTS 1 680 307 people born in Sweden between 1983 and 2000 to women who smoked (n=377 367, 22.5%) and did not smoke (n=1 302 940) in early pregnancy. Follow-up was until 31 December 2014. MAIN OUTCOME MEASURE Fractures by attained age up to 32 years. RESULTS During a median follow-up of 21.1 years, 377 970 fractures were observed (the overall incidence rate for fracture standardised by calendar year of birth was 11.8 per 1000 person years). The association between maternal smoking during pregnancy and risk of fracture in offspring differed by attained age. Maternal smoking was associated with a higher rate of fractures in offspring before 1 year of age in the entire cohort (birth year standardised fracture rates in those exposed and unexposed to maternal smoking were 1.59 and 1.28 per 1000 person years, respectively). After adjustment for potential confounders the hazard ratio for maternal smoking compared with no smoking was 1.27 (95% confidence interval 1.12 to 1.45). This association followed a dose dependent pattern (compared with no smoking, hazard ratios for 1-9 cigarettes/day and >= 10 cigarettes/day were 1.20 (95% confidence interval 1.03 to 1.39) and 1.41 (1.18 to 1.69), respectively) and persisted in within-sibship comparisons although with wider confidence intervals (compared with no smoking, 1.58 (1.01 to 2.46)). Maternal smoking during pregnancy was also associated with an increased fracture incidence in offspring from age 5 to 32 years in whole cohort analyses, but these associations did not follow a dose dependent gradient. In within-sibship analyses, which controls for confounding by measured and unmeasured shared familial factors, corresponding point estimates were all close to null. Maternal smoking was not associated with risk of fracture in offspring between the ages of 1 and 5 years in any of the models. CONCLUSION Prenatal exposure to maternal smoking is associated with an increased rate of fracture during the first year of life but does not seem to have a long lasting biological influence on fractures later in childhood and up to early adulthood.

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• Risk of depression following traumatic limb amputation-a general population-based cohort study

  2020. Helen Lindner, Scott Montgomery, Ayako Hiyoshi. Scandinavian Journal of Public Health 48 (3), 289-293

  Artikel

  Background: Individuals with traumatic limb amputation (TLA) may be at risk of depression, but evidence of increased depression after TLA from longitudinal studies has been limited. It is also unknown whether physical function, cognitive function, and employment prior to amputation affects depression risk. We aimed to examine longitudinal associations between TLA and depression in working age men, and to explore the role of pre-amputation occupational and individual characteristics. Methods: A Swedish national register-based cohort of 189,220 men born between 1952 and 1956, and who attended conscription assessments in adolescence, was followed from 1985 to 2009. Physical, cognitive, and psychological characteristics were measured at the conscription examination, and occupational information was obtained from the 1985 census. Main outcome measures were hospital inpatient and outpatient admissions for depression. Results: In total, 401 men underwent TLA; mean age at amputation was 42.5 years (SD 7.4). Cox regression produced an unadjusted hazard ratio (95% confidence interval) of 2.61 (1.62-4.21) for risk of subsequent depression associated with TLA compared with the general population. Adjustment for occupational, physical, cognitive, and psychological characteristics did not change the association much, producing a hazard ratio of 2.53 (1.57-4.08). Conclusions: TLA is associated with an increased risk of depression in men over more than two decades of follow up. Occupational and individual characteristics prior to amputation did not greatly change depression risk following amputation. We speculate that a coordinated combination of social support and medical management may help reduce persistent depression risk in men who experience amputation.

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• Acute effect of daily fine particulate matter pollution on cerebrovascular mortality in Shanghai, China

  2019. Khadija Akter Leepe (et al.). Environmental Science and Pollution Research 26 (25), 25491-25499

  Artikel

  Numerous studies have investigated the impacts of ambient fine particulate matter (PM2.5) on human health. In this study, we examined the association of daily PM2.5 concentrations with the number of deaths for the cerebrovascular disease on the same day, using the generalized additive model (GAM) controlling for temporal trend and meteorological variables. We used the data between 2012 and 2014 from Shanghai, China, where the adverse health effects of PM2.5 have been of particular concern. Three different approaches (principal component analysis, shrinkage smoothers, and the least absolute shrinkage and selection operator regularization) were used in GAM to handle multicollinear meteorological variables. Our results indicate that the average daily concentration of PM2.5 in Shanghai was high, 55 mu g/m(3), with an average daily death for cerebrovascular disease (CVD) of 62. There was 1.7% raised cerebrovascular disease deaths per 10 mu g/m(3) increase in PM2.5 concentration in the unadjusted model. However, PM2.5 concentration was no longer associated with CVD deaths after controlling for meteorological variables. The results were consistent in the three modelling techniques that we used. As a large number of people are exposed to air pollution, further investigation with longer time period including individual-level information is needed to examine the association.

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• Longitudinal analysis of loneliness and inflammation at older ages

  2019. Snieguole Vingeliene (et al.). Psychoneuroendocrinology 110

  Artikel

  Loneliness has been associated with adverse health outcomes, including age-related diseases with an inflammatory etiology such as cardiovascular disease. We aimed to identify potential biological pathways linking loneliness with morbidity and mortality by examining associations of loneliness with biomarkers. Participants in the English Longitudinal Study of Ageing (n = 3239) aged 50 years or older with an average age of 64 years, provided data in waves 4 (2008/2009) and 6 (2012/2013). Linear regression conditional change models had three outcomes: C reactive protein (CRP) measured in mg/L (log transformed), fibrinogen in g/L and ferritin in g/dL. In men, the onset of loneliness indicated by answering 'no' at wave 4 and 'yes' at wave 6 to question Much of the time during the past week, you felt lonely? was associated with a statistically significant increase in levels of CRP (beta = 0.36, 95% confidence interval (0.09 to 0.62)), plasma fibrinogen (0.18 (0.04 to 0.31)) and ferritin (41.04 (6.58 to 75.50)), after full adjustment. A statistically significant increase in CRP in men was also observed for onset of loneliness assessed with the question How often do you feel lonely? (0.20 (0.03 to 0.38)). These associations were not mediated by depressive symptoms. Persistent loneliness (loneliness experienced at both baseline and follow-up) assessed using the University of California Los Angeles (UCLA) loneliness scale was associated with an increase in CRP (0.11 (0.004 to 0.22)) among men. Associations of the two latter loneliness measures with fibrinogen and ferritin were mainly null. Among women, the only statistically significant association was for persistent loneliness (loneliness at both waves) identified by question Much of the time during the past week, you felt lonely? with a reduction in levels of ferritin (-20.62 (-39.78 to -1.46)). Men may be more susceptible to loneliness-associated disease risks signaled by biological changes, including systemic inflammation. Combined social and targeted medical interventions may help to reduce health risks associated with loneliness.

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• Shared unmeasured characteristics among siblings confound the association of Apgar score with stress resilience in adolescence

  2019. Cecilia Bergh (et al.). Acta Paediatrica 108 (11), 2001-2007

  Artikel

  Aim

  We investigated the association between low Apgar score, other perinatal characteristics and low stress resilience in adolescence. A within‐siblings analysis was used to tackle unmeasured shared familial confounding.

  Methods

  We used a national cohort of 527 763 males born in Sweden between 1973 and 1992 who undertook military conscription assessments at mean age of 18 years (17–20). Conscription examinations included a measure of stress resilience. Information on Apgar score and other perinatal characteristics was obtained through linkage with the Medical Birth Register. Analyses were conducted using ordinary least squares and fixed‐effects linear regression models adjusted for potential confounding factors.

  Results

  Infants with a prolonged low Apgar score at five minutes had an increased risk of low stress resilience in adolescence compared with those with highest scores at one minute, with an adjusted coefficient and 95% confidence interval of −0.26 (−0.39, −0.13). The associations were no longer statistically significant when using within‐siblings models. However, the associations with stress resilience and birthweight remained statistically significant in all analyses.

  Conclusion

  The association with low Apgar score seems to be explained by confounding due to shared childhood circumstances among siblings from the same family, while low birthweight is independently associated with low stress resilience.

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• Increasing income-based inequality in suicide mortality among working-age women and men, Sweden, 1990-2007

  2018. Ayako Hiyoshi, Naoki Kondo, Mikael Rostila. Journal of Epidemiology and Community Health 72 (11), 1009-1015

  Artikel

  Background Income inequalities have risen from the 1990s to 2000s, following the economic recession in 1994, but little research has investigated socioeconomic inequalities in suicide mortality for working-age men and women (aged between 30 and 64 years) over the time using longitudinal data in Sweden. Methods Using Swedish national register data between 1990 and 2007 as a series of repeated cohort studies with a 3-year follow-up (sample sizes were approximately 3.7 to 4.0million in each year), relative and slope indices of inequality (RII and SII respectively) based on quintiles of individual disposable income were calculated and tested for temporal trends. Results SII for the risk of suicide mortality ranged from 27.6 (95% CI 19.5 to 35.8) to 44.5 (36.3 to 52.6) in men and 5.2 (0.2 to 10.4) to 16.6 (10.7 to 22.4) in women (per 100000 population). In men, temporal trends in suicide inequalities were stable in SII but increasing in RII by 3% each year (p=0.002). In women, inequalities tended to increase in both RII and SII, especially after the late-1990s, with 10% increment in RII per year (p<0.001). Conclusions Despite universal social security and generous welfare provision, income inequalities in suicide were considerable and have widened, especially in women. The steeper rise in women may be partially related to higher job insecurity and poorer working conditions in the female dominated public sector after the recession. To reduce health consequences following an economic crisis and widened income inequalities, additional measures may be necessary in proportion to the levels of financial vulnerability.

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