Sex differences in the prognostic role of achieving target doses of heart failure medications: Data from the Swedish Heart Failure Registry.

AIMS: Guidelines recommend target doses (TD) of heart failure (HF) with reduced ejection fraction (HFrEF) medications regardless of sex. Differences in pharmacokinetics and pharmacodynamics may explain heterogeneity in treatment response, adverse reactions, and tolerability issues across sexes. The aim of this study was to explore sex-based differences in the association between TD achievement and mortality/morbidity in HFrEF. METHODS AND RESULTS: Patients with HFrEF and HF duration ≥6 months registered in the Swedish HF Registry between May 2000 and December 2020 (follow-up until December 2021) were analysed. Treatments of interest were renin-angiotensin system inhibitors (RASI) or angiotensin receptor-neprilysin inhibitors (ARNI), and beta-blockers. Multivariable Cox regression models were performed to explore the risk of cardiovascular mortality or hospitalization for HF across dose categories in females versus males. A total of 17 912 patients were analysed (median age 77.0 years, interquartile range [IQR] 70.0-83.0), 29% were female. Over a median follow-up of 1.33 years (IQR 0.29-3.22), for RASI/ARNI there was no significant difference in outcome for females achieving 50-99% versus 100% of TD (hazard ratio 0.92, 95% confidence interval 0.83-1.03), whereas males showed a gradual lowering in risk together with the achievement of higher % of TD (p-interaction = 0.030). For beta-blockers the achievement of TD was associated with the lowest risk of outcome regardless of sex. CONCLUSIONS: Our findings suggest that females and males might differently benefit from the same dose of RASI/ARNI, and do represent a general call for randomized controlled trials to consider sex-specific up-titration schemes when testing HFrEF treatments in need of up-titration.

Rolling the DICE (Design, Interpret, Compute, Estimate): Interactive Learning of Biostatistics With Simulations.

Despite the increasing relevance of statistics in health sciences, teaching styles in higher education are remarkably similar across disciplines: lectures covering the theory and methods, followed by application and computer exercises in given data sets. This often leads to challenges for students in comprehending fundamental statistical concepts essential for medical research. To address these challenges, we propose an engaging learning approach-DICE (design, interpret, compute, estimate)-aimed at enhancing the learning experience of statistics in public health and epidemiology. In introducing DICE, we guide readers through a practical example. Students will work in small groups to plan, generate, analyze, interpret, and communicate their own scientific investigation with simulations. With a focus on fundamental statistical concepts such as sampling variability, error probabilities, and the construction of statistical models, DICE offers a promising approach to learning how to combine substantive medical knowledge and statistical concepts. The materials in this paper, including the computer code, can be readily used as a hands-on tool for both teachers and students.

Multiple imputation of systematically missing data on gait speed in the Swedish National Study on Aging and Care.

BACKGROUND: There is insufficient investigation of multiple imputation for systematically missing discrete variables in individual participant data meta-analysis (IPDMA) with a small number of included studies. Therefore, this study aims to evaluate the performance of three multiple imputation strategies - fully conditional specification (FCS), multivariate normal (MVN), conditional quantile imputation (CQI) - on systematically missing data on gait speed in the Swedish National Study on Aging and Care (SNAC). METHODS: In total, 1 000 IPDMA were simulated with four prospective cohort studies based on the characteristics of the SNAC. The three multiple imputation strategies were analysed with a two-stage common-effect multivariable logistic model targeting the effect of three levels of gait speed (100% missing in one study) on 5-years mortality with common odds ratios set to OR1 = 0.55 (0.8-1.2 vs ≤0.8 m/s), and OR2 = 0.29 (>1.2 vs ≤0.8 m/s). RESULTS: The average combined estimate for the mortality odds ratio OR1 (relative bias %) were 0.58 (8.2%), 0.58 (7.5%), and 0.55 (0.7%) for the FCS, MVN, and CQI, respectively. The average combined estimate for the mortality odds ratio OR2 (relative bias %) were 0.30 (2.5%), 0.33 (10.0%), and 0.29 (0.9%) for the FCS, MVN, and CQI respectively. CONCLUSIONS: In our simulations of an IPDMA based on the SNAC where gait speed data was systematically missing in one study, all three imputation methods performed relatively well. The smallest bias was found for the CQI approach.

Prevalence and associated factors for poor mental health among young migrants in Sweden: a cross-sectional study.

BACKGROUND: Young migrants face multiple challenges that can affect their mental, sexual and reproductive health. OBJECTIVE: To assess the prevalence of self-reported poor mental health and its associated demographic, post-migration and sexual risk behaviour factors among young migrants (aged 15-25) in Sweden. METHODS: Data were drawn from a cross-sectional survey conducted with migrants aged 15-65 years old in Sweden between December 2018 and November 2019 (n = 6449). Among these, 990 participants aged 15-25 were eligible for the study. Mental health was measured using the Refugee Health Screener-13. Missing data indicator analysis and multivariable logistic regression models were conducted to estimate the association between mental health, sexual risk behaviour, demographic and migration-related variables. RESULTS: Of the 990 participants, 59% reported poor mental health. Participants reporting poor mental health were more likely to be female (AOR:1.63, 95% CI:1.18-2.25), to have lived in Sweden more than three years (AOR:2.16, 95% CI:1.17-3.97), to engage in any sexual risk behaviour (AOR:1.99, 95% CI:1.25-3.17), and to live alone (AOR:1.95, 95% CI:1.25-3.03) or with friends they already knew (AOR:1.60, 95% CI:1.37-4.91). People arriving from the Americas (AOR:0.54, 95% CI:0.33-0.88), Asia (AOR:0.44, 95% CI:0.22-0.86), Europe (AOR:0.30, 95% CI:0.14-0.61) and Africa (AOR 0.37, 95% CI: 0.23-0.60) had lower odds of poor mental health than those arriving from Syria. CONCLUSION: The prevalence of poor mental health among young migrants in Sweden was high, with specific subgroups (women, asylum seekers, people arriving from Syria, and those residing longer in Sweden) being particularly vulnerable. Our results indicate the interconnectedness between poor mental health and sexual risk behaviour in this population. Thus, policies targeting young migrants should ensure that healthcare services screen for both poor sexual and mental health at the same time.

A probabilistic bias analysis on the magnitude of unmeasured confounding: The impact of driving mileage on road traffic crashes.

INTRODUCTION: Unmeasured confounding can lead to biased interpretations of empirical findings. This paper aimed to assess the magnitude of suspected unmeasured confounding due to driving mileage and simulate the statistical power required to detect a discrepancy in the effect of polypharmacy on road traffic crashes (RTCs) among older adults. METHODS: Based on Monte Carlo Simulation (MCS) approach, we estimated 1) the magnitude of confounding of driving mileage on the association of polypharmacy and RTCs and 2) the statistical power of to detect a discrepancy from no adjusted effect. A total of 1000 studies, each of 500000 observations, were simulated. RESULTS: Under the assumption of a modest adjusted exposure-outcome odds ratio of 1.35, the magnitude of confounding bias by driving mileage was estimated to be 16% higher with a statistical power of 50%. Only an adjusted odds ratio of at least 1.60 would be associated with a statistical power of about 80% CONCLUSION: This applied probabilistic bias analysis showed that not adjusting for driving mileage as a confounder can lead to an overestimation of the effect of polypharmacy on RTCs in older adults. Even considering a large sample, small to moderate adjusted exposure effects were difficult to be detected.

Prevalence of children under five with disabilities in Sierra Leone in 2017: Insights from a population-based multiple indicator cluster survey.

BACKGROUND: Children with disabilities have been low on the agenda of child health, including in Sierra Leone, and there are still many gaps in our knowledge and understanding of the issue. OBJECTIVE: To estimate the prevalence of children with disabilities in Sierra Leone using functional difficulty as a proxy and to understand the factors associated with disabilities among children two to four years living in Sierra Leone. METHODS: We used cross-sectional data from the Sierra Leone 2017 Multiple Indicator Cluster Survey. Disability was defined using a functional difficulty definition with additional thresholds used to define children with severe functional difficulty and multiple disabilities. Logistic regression models estimated odds ratios (ORs) of childhood disability and how they were associated with socioeconomic factors and living conditions. RESULTS: Prevalence of children with disabilities was 6.6% (95% confidence interval (CI) 5.8-7.6%) and there was a high risk of comorbidity between different functional difficulties. Children with disabilities were less likely to be girls (adjusted odds ratio (AOR) 0.8 (CI 0.7-1.0) and older (AOR 0.3 (CI 0.2-0.4)), but more prone to be stunted (AOR 1.4 (CI 1.1-1.7)) and have younger caregivers (AOR 1.3 (CI 0.7-2.3)). CONCLUSION: The prevalence of disabilities in young Sierra Leonean children was comparable to other countries in West and Central Africa when using the same measure of disability. Preventive as well as early detection and intervention efforts are recommended to be integrated with other programs, e.g vaccinations, nutrition, and poverty reducing programs.

Does misclassification of former tobacco smokers explain the 'smoker's paradox' in the risk of COVID-19? Insights from the Stockholm Public Health Cohort.

BACKGROUND: The association between tobacco smoking and the risk of COVID-19 and its adverse outcomes is controversial, as studies reported contrasting findings. Bias due to misclassification of the exposure in the analyses of current versus non-current smoking could be a possible explanation because former smokers may have higher background risks of the disease due to co-morbidity. The aim of the study was to investigate the extent of this potential bias by separating non-, former, and current smokers when assessing the risk or prognosis of diseases. METHODS: We analysed data from 43,400 participants in the Stockholm Public Health Cohort, Sweden, with information on smoking obtained prior to the pandemic. We estimated the risk of COVID-19, hospital admissions and death for (a) former and current smokers relative to non-smokers, (b) current smokers relative to non-current smokers, that is, including former smokers; adjusting for potential confounders (aRR). RESULTS: The aRR of a COVID-19 diagnosis was elevated for former smokers compared with non-smokers (1.07; 95% confidence interval (CI) =1.00-1.15); including hospital admission with any COVID-19 diagnosis (aRR= 1.23; 95% CI = 1.03-1.48); or with COVID-19 as the main diagnosis (aRR=1.23, 95% CI= 1.01-1.49); and death within 30 days with COVID-19 as the main or a contributory cause (aRR=1.40; 95% CI=1.00-1.95). Current smoking was negatively associated with risk of COVID-19 (aRR=0.79; 95% CI=0.68-0.91). CONCLUSIONS: Separating non-smokers from former smokers when assessing the disease risk or prognosis is essential to avoid bias. However, the negative association between current smoking and the risk of COVID-19 could not be entirely explained by misclassification.

The influence of meteorological factors on COVID-19 spread in Italy during the first and second wave.

The relation between meteorological factors and COVID-19 spread remains uncertain, particularly with regard to the role of temperature, relative humidity and solar ultraviolet (UV) radiation. To assess this relation, we investigated disease spread within Italy during 2020. The pandemic had a large and early impact in Italy, and during 2020 the effects of vaccination and viral variants had not yet complicated the dynamics. We used non-linear, spline-based Poisson regression of modeled temperature, UV and relative humidity, adjusting for mobility patterns and additional confounders, to estimate daily rates of COVID-19 new cases, hospital and intensive care unit admissions, and deaths during the two waves of the pandemic in Italy during 2020. We found little association between relative humidity and COVID-19 endpoints in both waves, whereas UV radiation above 40 kJ/m2 showed a weak inverse association with hospital and ICU admissions in the first wave, and a stronger relation with all COVID-19 endpoints in the second wave. Temperature above 283 K (10 °C/50 °F) showed a strong non-linear negative relation with COVID-19 endpoints, with inconsistent relations below this cutpoint in the two waves. Given the biological plausibility of a relation between temperature and COVID-19, these data add support to the proposition that temperature above 283 K, and possibly high levels of solar UV radiation, reduced COVID-19 spread.

Diagnosing acute mastoiditis in a Pediatric Emergency Department: a retrospective review.

Background and aim Acute mastoiditis (AM) is a common complication of acute otitis media in children. There is currently no consensus on criteria for diagnosis. Head CT is the most frequent diagnostic tool used in the ED although the increasing awareness on the use of ionized radiations in children has questioned the use of CT imaging versus solely using clinical criteria. Our research aimed to understand if CT imaging was essential in making a diagnosis of AM. Methods We retrospectively analyzed medical records from pediatric patients who accessed our Pediatric Emergency Department (ED) between January 2014 and December 2020, with a clinical suspicion of AM. We reviewed clinical symptoms upon presentation, head CT and lab values (white blood cell count or WBC, C-Reactive Protein or CRP) when done, presence of complications and discharge diagnosis. A multilogistic regression model was specified to establish the role of clinical features and of CT in the diagnosis of AM based on 77 patients. Results Otalgia (OR= 5.01; 95% CI= 1.52-16.51), protrusion of the auricle (OR= 8.42; 95% CI= 1.37-51.64) and hyperemia (OR= 4.07; 95% CI= 1.09-15.23) of the mastoid were the symptoms strongly associated with a higher probability of AM. In addition to clinical features, the adjusted OR conferred by head CT was 3.09 (95% CI = 0.92-10.34). Conclusions Clinical signs were most likely predictive of AM in our sample when compared to Head CT. Most common symptoms were protrusion of the auricle, hyperemia or swelling behind the ear and otalgia.

Iron deficiency in heart failure: screening, prevalence, incidence and outcome data from the Swedish Heart Failure Registry and the Stockholm CREAtinine Measurements collaborative project.

AIMS: Iron deficiency (ID) is common in heart failure (HF) and linked with poor prognosis regardless of anaemia. We assessed temporal trends in ID testing, ID prevalence, ID incidence, iron need, and outcomes associated with ID in HF across the ejection fraction (EF) spectrum. METHODS AND RESULTS: From the Swedish HF registry, we enrolled 15 197 patients from Region Stockholm with available EF and collected laboratory tests from routine practice. Iron screening improved since 2016 but remained <25% as of 2018. In 1486 patients with iron biomarkers at baseline, the prevalence of ID was 55% (HF with reduced EF 54%; mildly reduced EF 51%; preserved EF 61%). Iron need was ≥1500 mg in 72% of patients. ID was independently associated with higher risk for HF rehospitalizations (incidence rate ratio [IRR] 1.62, 95% confidence interval [CI] 1.13-2.31) and with cardiovascular (CV) death or repeated HF hospitalizations (IRR 1.63, 95% CI 1.15-2.30) regardless of EF (p-interaction 0.21 and 0.26, respectively), but not with all-cause death, CV death, or first HF hospitalization. Among 96 patients without ID at baseline and with follow-up iron biomarkers, 21% developed ID within 6 months. CONCLUSIONS: Iron deficiency screening improved over time but is still limitedly implemented, despite being highly prevalent and incident, and independently associated with CV death or HF rehospitalizations regardless of EF. Most patients with ID had an iron need necessitating either repeated administrations of intravenous iron or a preparation permitting >1000 mg doses. These data highlight the need for improved screening for ID in HF.

Knowledge of the abortion law and key legal issues of sexual and reproductive health and rights among recently arrived migrants in Sweden: a cross-sectional survey.

BACKGROUND: Sexual and reproductive health and rights (SRHR), including access and information on the laws and policies related to abortion, varies considerably between countries. Migrants may have limited knowledge of SRHR and related resources in their new country. This study investigates migrants' knowledge of the right to safe and legal abortion and other associated factors including the recent law on sexual consent, the legal age for sexual consent and age to marry in Sweden. METHODS: We conducted a cross-sectional study from 2018 to 2019 among recent migrants attending high schools or Swedish language schools. Descriptive statistics were computed on the knowledge of the Swedish abortion law and other legal aspects. Univariable and multivariable logistic regression analyses were conducted to assess if migrants' socio-demographic characteristics were associated with knowledge (i.e. correct/incorrect) of the Swedish abortion law and other key SRHR-related legal issues. RESULTS: Of the total 6,263 participants, 3,557 (57%) responded about whether it is legal to have an induced abortion in Sweden, and of these, 2,632 (74%) answered incorrectly. While more than half (61%) of the respondents knew the sexual consent law, nearly half (48%) did not know that sexual consent is also required for married couples. About 90% correctly responded that it is illegal to have sex with a minor (under the age of 15) and were aware of the legal age (18 years) to marry in Sweden. Incorrect knowledge of the Swedish abortion law was associated with being religious (adjusted odds ratio (AOR), 2.12; 95% confidence interval (CI), 1.42-3.15), not having previous sexual health education (AOR, 1.68; 95% CI, 1.38-2.05), coming from a country with predominantly restrictive abortion laws (AOR, 1.46; 95% CI, 1.16-1.84), low level of education (AOR, 1.29; 95% CI, 1.04-1.61) and having a temporary residence permit (AOR, 1.27; 95% CI, 1.02-1.57). CONCLUSION: We found a substantial lack of knowledge among migrants of reproductive age in Sweden regarding important laws and policies of SRHR, particularly the right to abortion. SRHR-related programmes and comprehensive sexual health education for recently arrived migrants could include components to increase knowledge of legal and safe abortions and other laws concerning SRHR.

Use of and association between heart failure pharmacological treatments and outcomes in obese versus non-obese patients with heart failure with reduced ejection fraction: data from the Swedish Heart Failure Registry.

AIMS: To investigate the use of guideline-directed medical therapies (GDMT) and associated outcomes in obese (body mass index ≥30 kg/m2 ) versus non-obese patients with heart failure (HF) with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Patients with HFrEF from the Swedish HF Registry were included. Of 16 116 patients, 24% were obese. In obese versus non-obese patients, use of treatments was 91% versus 86% for renin-angiotensin system inhibitors (RASi)/angiotensin receptor-neprilysin inhibitors (ARNi), 94% versus 91% for beta-blockers, 53% versus 43% for mineralocorticoid receptor antagonists. Obesity was shown to be independently associated with more likely use of each treatment, triple combination therapy, and the achievement of target dose by multivariable logistic regressions. Multivariable Cox regressions showed use of RASi/ARNi and beta-blockers being independently associated with lower risk of all-cause/cardiovascular death regardless of obesity, although, when considering competing risks, a lower risk of cardiovascular death with RASi/ARNi in obese versus non-obese patients was observed. RASi/ARNi were associated with lower risk of HF hospitalization in obese but not in non-obese patients, whereas beta-blockers were not associated with the risk of HF hospitalization regardless of obesity. At the competing risk analysis, RASi/ARNi use was associated with higher risk of HF hospitalization regardless of obesity. CONCLUSION: Obese patients were more likely to receive optimal treatments after adjustment for factors affecting tolerability, suggesting that perceived beyond actual tolerance issues limit GDMT implementation. RASi/ARNi and beta-blockers were associated with lower mortality regardless of obesity, with a greater association between RASi/ARNi and lower cardiovascular death in obese versus non-obese patients when considering competing risk.

Can dementia risk be reduced by following the American Heart Association's Life's Simple 7? A systematic review and dose-response meta-analysis.

This study aimed to quantify the relationships between the American Heart Association (AHA) Cardiovascular Health (CVH) metrics, namely AHA Life's Simple 7, and cognitive outcomes. We searched PubMed and Embase (January 1, 2010-August 24, 2022) and finally included 14 longitudinal studies (311654 participants with 8006 incident dementia cases). Random-effects meta-analysis and one-stage linear mixed-effects models were performed. Increased CVH score seemed to associate with decreased risk of incident dementia in a linear manner, but this relationship varied by the measurement age of CVH metrics. That is, midlife CVH tended to have a linear association with late-life dementia risk, whereas a J-shaped association was observed between the late-life CVH score and dementia. In addition, late-life dementia risk was reduced significantly if individuals maintained an ideal level of AHA's CVH guidelines of physical activity, fasting plasma glucose, total cholesterol, and smoking. However, our meta-analysis did not show a significant association between CVH score and global cognitive decline rate. Following AHA's CVH guidelines and maintaining CVH at an optimal level would substantially reduce the late-life dementia risk. More research is required to explore the link between a favorable CVH score and cognitive trajectories among cognitively asymptomatic older populations.

Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis.

BACKGROUND: We investigated the causality of IL-8 on carotid intima-media thickness (c-IMT), a measure of sub-clinical atherosclerosis. METHODS: The IMPROVE is a multicenter European study (n = 3,711). The association of plasma IL-8 with c-IMT (mm) was estimated by quantile regression. Genotyping was performed using the Illumina CardioMetabo and Immuno chips. Replication was attempted in three independent studies and a meta-analysis was performed using a random model. RESULTS: In IMPROVE, each unit increase in plasma IL-8 was associated with an increase in median c-IMT measures (all p<0·03) in multivariable analyses. Linear regression identified rs117518778 and rs8057084 as associated with IL-8 levels and with measures of c-IMT. The two SNPs were combined in an IL-8-increasing genetic risk that showed causality of IL-8 on c-IMT in IMPROVE and in the UK Biobank (n = 22,179). The effect of IL-8 on c-IMT measures was confirmed in PIVUS (n = 1,016) and MDCCC (n = 6,103). The association of rs8057084 with c-IMT was confirmed in PIVUS and UK Biobank with a pooled estimate effect (ß) of -0·006 with 95%CI (-0·008- -0·003). CONCLUSION: Our results indicate that genetic variants associated with plasma IL-8 also associate with c-IMT. However, we cannot infer causality of this association, as these variants lie outside of the IL8 locus.

Vertical HIV transmission within 18 months post partum among women on lifelong antiretroviral therapy for HIV in Dar es Salaam, Tanzania: a prospective cohort study.

BACKGROUND: The UNAIDS estimate of vertical HIV transmission in Tanzania is high (11%), despite 84% uptake of antiretroviral therapy (ART) among pregnant women with HIV. We aimed to evaluate vertical transmission and its determinants by 18 months post partum among women on lifelong ART in routine health-care settings in Tanzania. METHODS: We conducted a prospective cohort study in 226 health facitilies across Dar-es-Salaam, Tanzania. Eligible participants were pregnant women of any age with HIV, and later their infants, who enrolled in routine health-care services for the prevention of vertical transmission. We prospectively followed up mother-infant pairs at routine monthly visits until 18 months post partum and extracted data from the care and treatment clinic (CTC2) database, a national electronic database that stores patient-level HIV care and treatment clinic data. The primary outcome was time from birth to HIV diagnosis, defined as a positive infant HIV DNA PCR or antibody test from age 18 months. We used the Kaplan-Meier method to estimate cumulative risk of vertical transmission by 18 months post partum and Cox proportional hazards regression with shared frailties to account for potential clustering in health facilities to evaluate predictors of transmission. FINDINGS: Between Jan 1, 2015, and Dec 31, 2017, 22 930 pregnant women with HIV (median age 30 years, IQR 25-34) enrolled on a care programme. After excluding 9140 (39·9%) women and 539 (2·4%) infants with missing outcome data, 13 251 (59·0%) mother-infant pairs were analysed, of whom 6072 (45·8%) women were already on ART before pregnancy. By 18 months post partum, 159 (1·2%) of 13 251 infants were diagnosed with HIV, equivalent to a risk of vertical transmission of 1·4% (95% CI 1·2-1·6). In the complete case analysis, the rates of vertical transmission were higher among women who enrolled in the third trimester of pregnancy than among those who enrolled in the first trimester (adjusted hazard ratio 3·01, 95% CI 1·59-5·70; p=0·0003), among women with advanced HIV disease than among those with early-stage disease (1·89, 1·22-2·93; p=0·0046), and among women who were on a second-line ART regimen than among those on a first-line regimen (3·58, 1·08-11·82; p=0·037). By contrast, the rate of vertical transmission was lower among women who were already on ART at enrolment than among those starting ART at enrolment (0·39, 0·25-0·60; p<0·0001) as well as among women in high-volume clinics than among those in low-volume clinics (0·46 (0·24-0·90; p<0·0097). INTERPRETATION: Provision of ART for life (WHO's option B+ recommendation) has reduced the risk of vertical transmission to less than 2% among pregnant women with HIV in routine care settings in urban Tanzania. There is still a need to improve timely HIV diagnosis and ART uptake, and to optimise follow-up for the prevention of vertical transmission and the uptake of infant HIV testing. FUNDING: Swedish International Development Cooperation Agency.

Socio-demographic differences in polypharmacy and potentially inappropriate drug use among older people with different care needs and in care settings in Stockholm, Sweden.

AIMS: Polypharmacy and potentially inappropriate medications (PIM) are risk factors for negative health outcomes among older people. This study aimed to investigate socio-demographic differences in polypharmacy and PIM use among older people with different care needs in a standard versus an integrated care setting. METHODS: Population-based register data on residents aged ⩾65 years in Stockholm County based on socio-demographic background and social care use in 2014 was linked to prescription drug use in 2015. A logistic regression analysis was used to estimate socio-demographic differences in polypharmacy and PIM, adjusting for education, age group, sex, country of birth, living alone, morbidity and dementia by care setting based on area and by care need (i.e. independent, home help or institutionalised). RESULTS: The prevalence of polypharmacy and PIM was greater among home-help users (60.4% and 11.5% respectively) and institutional residents (74.4% and 11.9%, respectively). However, there were greater socio-demographic differences among the independent, with those with lower education, older age and females having higher odds of polypharmacy and PIM. Morbidity was a driver of polypharmacy (odds ratio (OR)=1.19, confidence interval (CI) 1.16-1.22) among home-help users. Dementia diagnosis was associated with reduced odds of polypharmacy and PIM among those in institutions (OR=0.78, CI 0.71-0.87 and OR 0.52, CI 0.45-0.59, respectively) and of PIM among home-help users (OR=0.53, 95% CI 0.42-0.67). CONCLUSIONS: Polypharmacy and PIM were associated with care needs, most prevalent among home-help users and institutional residents, but socio-demographic differences were most prominent among those living independently, suggesting that municipal care might reduce differences between socio-demographic groups. Care setting had little effect on inappropriate drug use, indicating that national guidelines are followed.

Antithrombotic treatment switching in elderly patients with atrial fibrillation and the risk of thromboembolism, bleeding, and cardiac death.

Background: Risks of antithrombotic switching is not investigated in elderly atrial fibrillation patients. Objectives: To investigate the effectiveness and safety of antithrombotic treatment and switching of antithrombotic treatment in elderly patients (aged 75 years or older) with atrial fibrillation (AF). Methods: We conducted a cohort study of 2943 patients with AF (Carrebean-elderly), hospitalized during 2010-2017. Cox models were used to estimate the association of antithrombotic treatment (warfarin, direct oral anticoagulants [DOAC] and non-guideline-recommended therapy [NG], i.e., aspirin and low-molecular-weight heparin) at discharge and antithrombotic treatment switching during follow-up with the risk of a composite and single end points of thromboembolism, bleeding, and cardiac death. Crude and adjusted risk estimates were expressed as hazard ratios (HRs) with 95% confidence intervals (CIs). All-cause death was evaluated, with competing risk regression and estimates expressed as subhazard ratios and 95% CIs. Results: We observed an increased risk for the composite end point associated with NG as compared to warfarin at discharge (HR, 1.18; 95% CI, 1.01-1.38) with congruent competing risk regression results, while no significant risk difference was seen for DOACs compared to warfarin (HR, 1.12; 95% CI, 0.92-1.36). Switching from NG to warfarin/DOAC and from warfarin to DOAC occurred in 30.4% and 33.1% of respective antithrombotic treatment groups at discharge and was associated with a decreased risk for the composite end point with an adjusted HR of 0.45 (95% CI, 0.32-0.63) and a HR of 0.50 (95% CI, 0.38-0.65), respectively. Conclusions: Antithrombotic treatment switching is common in the elderly AF population. Importantly, switching to guideline-recommended treatment has a favorable impact on both effectiveness and safety.

Interaction Analysis Based on Shapley Values and Extreme Gradient Boosting: A Realistic Simulation and Application to a Large Epidemiological Prospective Study.

Background: SHapley Additive exPlanations (SHAP) based on tree-based machine learning methods have been proposed to interpret interactions between exposures in observational studies, but their performance in realistic simulations is seldom evaluated. Methods: Data from population-based cohorts in Sweden of 47,770 men and women with complete baseline information on diet and lifestyles were used to inform a realistic simulation in 3 scenarios of small (ORM = 0.75 vs. ORW = 0.70), moderate (ORM = 0.75 vs. ORW = 0.65), and large (ORM = 0.75 vs. ORW = 0.60) discrepancies in the adjusted mortality odds ratios conferred by a healthy diet among men and among women. Estimates were obtained with logistic regression (L-ORM; L-ORW) and derived from SHAP values (S-ORM; S-ORW). Results: The sensitivities of detecting small, moderate, and large discrepancies were 28, 83, and 100%, respectively. The sensitivities of a positive sign (L-ORW > L-ORM) in the 3 scenarios were 93, 100, and 100%, respectively. Similarly, the sensitivities of a positive discrepancy based on SHAP values (S-ORW > S-ORM) were 86, 99, and 100%, respectively. Conclusions: In a realistic simulation study, the ability of the SHAP values to detect an interaction effect was proportional to its magnitude. In contrast, the ability to identify the sign or direction of such interaction effect was very high in all the simulated scenarios.

Ion channel inhibition with amiodarone or verapamil in symptomatic hospitalized nonintensive-care COVID-19 patients: The ReCOVery-SIRIO randomized trial.

BACKGROUND: Ion channel inhibition may offer protection against coronavirus disease 2019 (COVID-19). Inflammation and reduced platelet count occur during COVID-19 but precise quantification of risk thresholds is unclear. The Recov ery-SIRIO study aimed to assess clinical effects of amiodarone and verapamil and to relate patient phenotypes to outcomes. METHODS: RECOVERY-SIRIO is a multicenter open-label 1:1:1 investigator-initiated randomized trial with blinded event adjudication. A sample of 804 symptomatic hospitalized nonintensive-care COVID-19 patients, follow-up for 28 days was initially planned. RESULTS: The trial was stopped when a total of 215 patients had been randomized to amiodarone (n = 71), verapamil (n = 72) or standard care alone (n = 72). At 15 days, the hazard ratio (hazard ratio [HR], 95% confidence interval [CI]) for clinical improvement was 0.77 (0.52-1.14) with amiodarone and 0.97 (0.81-1.17) with verapamil as compared to usual care. Clinically relevant associations were found between mortality or lack of clinical improvement and higher peak C-reactive protein (CRP) levels or nadir platelet count at 7, 10 and 15 days. Mortality rate increased by 73% every 5 mg/dL increment in peak CRP (HR 1.73, 95% CI 1.27-2.37) and was two-fold higher for every decrement of 100 units in nadir platelet count (HR 2.19, 95% CI 1.37-3.51). By cluster analysis, thresholds of 5 mg/dL for peak CRP and 187 × 103/mcL for nadir platelet count identified the phenogroup at greatest risk of dying. CONCLUSIONS: In this randomized trial, neither amiodarone nor verapamil were found to significantly accelerate short-term clinical improvement. Peak CRP and nadir platelet counts were associated with increased mortality both in isolation and by cluster analysis.

Socioeconomic differences in inpatient care expenditure in the last year of life among older people: a retrospective population-based study in Stockholm County.

OBJECTIVES: To investigate the association between inpatient care expenditure (ICE) and income group and the effect of demographic factors, health status, healthcare and social care utilisation on ICE in the last year of life. DESIGN: Retrospective population-based study. SETTING: Stockholm County. PARTICIPANTS: Decedents ≥65 years in 2015 (N=13 538). OUTCOME: ICE was calculated individually for the month of, and 12 months preceding death using healthcare register data from 2014 and 2015. ICE included the costs of admission and treatment in inpatient care adjusted for the price level in 2018. RESULTS: There were difference between income groups and ICE incurred at the 75th percentile, while a social gradient was found at the 95th percentile where the highest income group incurred higher ICE (SEK45 307, 95% CI SEK12 055 to SEK79 559) compared with the lowest income groups. Incurring higher ICE at the 95th percentile was driven by greater morbidity (SEK20 333, 95% CI SEK12 673 to SEK29 993) and emergency department care visits (SEK77 995, 95% CI SEK64 442 to SEK79 549), while lower ICE across the distribution was associated with older age and residing in institutional care. CONCLUSION: Gaining insight into patterns of healthcare expenditure in the last year of life has important implications for policy, particularly as socioeconomic differences were visible in ICE at a time of greater care need for all. Future policies should focus on engaging in advanced care planning and strengthening the coordination of care for older people.