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Objective: To analyse comorbidity measures in relation to cardiovascular disease risk, using data from Swedish healthcare registries. The aim was to evaluate the performance of different indices in predicting incidences of four outcomes: coronary heart disease (CHD), myocardial infarction (MI), heart failure (HF) and stroke.

Methods: Study population: All individuals in Sweden born between 1936 and 1975, with a look-back for diagnosis data 2010-2014 and followed-up for outcomes from 2024 to 2019, n=4 454 895 individuals. Two age groups: 40-64 and 65-79 years old were studied. We used the area under the receiver operating characteristic curves (AUROC) of age-and-sex, the Nordic Multimorbidity Index (NMI), a set of five cardiovascular risk factors as indicator variables (CV-IV) and explored measures based on inpatient care and numbers of filled prescriptions.

Results: In the age group 40-64 years, the AUROCs for age-and-sex alone were higher than those for the indices alone in all analyses: CHD (0.739); MI (0.736); HF (0.730) and stroke (0.685). CV-IV alone showed a higher AUROC for HF (0.694; 95% CI 0.690 to 0.697) than that for NMI (0.643; 95% CI 0.639 to 0.647), and for numbers of filled prescriptions (0.671; 95% CI 0.667 to 0.675).

Highest AUROC was observed for HF, when taking age-and-sex into account, for CV-IV (0.781; 95% CI 0.778 to 0.784) followed by numbers of filled prescriptions (0.776; 95% CI 0.773 to 0.780) and NMI (0.771; 95% CI 0.768 to 0.774). Furthermore, AUROC was higher for CV-IV, when taking age-and-sex into account, than that of age-and-sex alone for all outcomes in both age groups.

Conclusion: AUROC for age-and-sex alone was higher than that for any other single measure alone for all outcomes. The highest AUROC observed was for CV-IV adjusted for age-and-sex for HF. Thus, simple indicators measuring a few well-established cardiovascular risk factors outperformed a complex index such as the NMI. Similar results were obtained for numbers of filled prescriptions implying possible use as a proxy measure for comorbidity.

Objectives

The aim of the present study was to compare Area Under the Receiver Operating Characteristic curves (AUROCs) of age-and-sex alone, and in addition respectively, the Nordic Multimorbidity Index (NMI), Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI), and explore simple count-based measures on in-patient care and filled drug prescriptions, with the outcome mortality using Swedish health registries.

Study design and setting Study population

All persons born in 1975 or earlier who were continuously resident in Sweden between 1 January 2010 and 31 December 2014 (n=5 010 261) with a follow-up for all-cause mortality from 1 January 2015 to 31 December 2019.

Methods

AUROCs were calculated with 1- to 5-year-look-back for age-and-sex, each index and explored measures for 1- to 5-year mortality. Results AUROC was for age-and-sex alone for 5-year mortality 0.8731. Age-and-sex alone outperformed, respectively: NMI, difference in AUROC, 0.0695 (95% CI 0.0687 to 0.0704); CCI, 0.1509 (95% CI 0.1500 to 0.1518) and ECI 0.1631 (95% CI 0.1622 to 0.1640). AUROC for NMI when added to age-and-sex, 0.9072 was marginally higher than age-and-sex alone. AUROC for explored measures as numbers of hospitalisations, days hospitalised, or numbers of filled drug prescriptions were around 0.75-0.80 and when added to age-and-sex around 0.90.

Conclusion

Age-and-sex alone showed higher AUROC than any other measure alone and NMI provides modest additional discrimination, with CCI and ECI both less helpful, that is, informative. Explored measures; days hospitalised or numbers of filled prescriptions rendered AUROC of somewhat lower magnitude when added to age-and-sex. Thus, the latter could be considered for use in addition to age-and-sex when full background data are lacking.

Objective: The aim of this review is to describe the regulatory background of the COVID-19 vaccines, the national recommendations for use issued and vaccine uptake in Sweden. It includes an overview of licensing and relevant safety aspects identified by the European Medicines Agency (EMA) and the national vaccination plan issued by the Public Health Agency (PHA) of Sweden.

Materials and methods: Information on dates of licensing and safety aspects of importance identified by EMA published on its website, was compiled and presented in a chronological order. National recommendations on COVID-19-vaccination and vaccinations-data on uptake and coverage using the national-vaccine-register are presented.

Results: COVID-19 vaccines development, assessments using rolling review and licensing of the covid-19 vaccines was done in 2020 during less than a year. Large-scale production was implemented. Monthly safety reviews performed by the EMA identified risk for thrombosis with thrombocytopenia syndrome with adenoviral vaccines and myocarditis for mRNA vaccines which led to restrictions in national recommendations for specified groups. National vaccinations were launched in a phased manner during 2021. Persons of high age, risk groups and nursing home personnel were prioritised during primary vaccinations and for initial boosters. In the Swedish population, 85% recieved at least one vaccine dose from the age of 12. At least two doses were recieved by 81% from age 18 and 95% from age 80.

Conclusion: Recommendations for national use adhered to relevant adverse drug reactions identified. The vaccine coverage was high. Timelines presented should be considered in follow-up studies of COVID-19-vaccines to manage possible selection bias and confounding.

Background: With the increasing global burden of type 2 diabetes, prevention strategies that target prediabetes, a state of hyperglycaemia that puts individuals at high risk of type 2 diabetes, are required. We aimed to estimate global rates of transition from prediabetes to normoglycaemia or type 2 diabetes, stratified by age, sex, and race and ethnicity. We also aimed to quantify the effect of modifiable and non-modifiable risk factors on these transitions.

Methods: In this pooled analysis of individual-level data, we included original data from 19 prospective cohort studies conducted in Asia (Iran and Japan), Australia, Europe (Spain and Sweden), North America (USA and Mexico), and South America (Venezuela). We applied discrete-time hidden Markov models to estimate rates and ratios of prediabetes transitions to type 2 diabetes and normoglycaemia specific to age, sex, and race and ethnicity. We used Fine-Gray competing risk models to derive cohort-specific subhazard ratios (SHRs) for potential risk factors influencing these transitions. We subsequently pooled these SHRs using a random-effects meta-analysis. In subgroup analyses stratified by age, sex, race and ethnicity, and recruitment period, we used multivariate Cox models to investigate the degree of heterogeneity between studies.

Findings: 76 092 participants (39 842 [52·3%] women and 36 250 [47·6%] men; mean age 51·1 years [SD 12·7]) with available data on glycaemic status from at least one follow-up visit were included in the analysis, of whom 56 837 (74·7%) had normoglycaemia and 19 255 (25·3%) had prediabetes. Median follow-up was 9·8 years (IQR 5·8-12·5). Within 10 years, individuals with prediabetes had a 12·5% probability of progressing to type 2 diabetes, whereas the probability of reverting to normoglycaemia was 36·1%. However, in the highest fasting plasma glucose quartile, the probability of progression increased to 16·1% and reversion decreased to 13·4%. Male sex, older age (≥ 55 years), and Latinx populations were associated with an increased risk of transitioning to type 2 diabetes. Risk factors that significantly reduced prediabetes reversion to normoglycaemia were overweight (SHR 0·88 [95% CI 0·76-0·99]), obesity (0·66 [0·52-0·81]), elevated waist-to-height ratio (0·82 [0·70-0·95]), elevated waist-to-hip ratio (0·79 [0·68-0·91]), and reduced HDL concentration (0·72 [0·59-0·84]).

Interpretation: Our findings highlight that reversion to normoglycaemia was more common than progression to type 2 diabetes among individuals with prediabetes, and that these transitions were strongly influenced by modifiable risk factors. The increased risk of progression with advancing age and among men underscores the importance of early identification and targeted interventions in population groups at high risk of type 2 diabetes. Furthermore, the elevated progression risk in individuals with higher fasting plasma glucose concentrations at baseline reinforces the need for timely detection and intervention during this crucial clinical window. 

Background and Objectives: Reports of suspected adverse drug reactions are of a great importance for the safety monitoring of new vaccines to identify potential safety risks promptly and to ensure necessary measures for risk mitigation. We reviewed the reports of fatal adverse drug reactions after coronavirus disease 2019 (COVID-19) vaccination with Comirnaty (R), Spikevax (R), and Vaxzevria (R) during the national vaccination campaign in Sweden.

Methods: Swedish reports of suspected adverse drug reactions with fatal outcomes after COVID-19 vaccines were retrieved from the EudraVigilance database. Vaccination data were obtained from the National vaccination register. Reporting rates were calculated by dividing the number of adverse drug reaction reports with fatal outcomes by the number of people exposed to at least one dose of the COVID-19 vaccines or by the number of vaccine doses given. A causality assessment of adverse drug reaction reports was performed by clinically qualified reviewers.

Results: More than 26 million doses of COVID-19 vaccines were administered and 456 reports of suspected adverse drug reactions with fatal outcomes were reported during 27 December, 2020-31 May, 2023. The reporting rate was 5.7 fatal outcomes per 100,000 persons vaccinated with at least one dose of any COVID-19 vaccine or 1.7 per 100,000 vaccine doses given. Most of the fatalities were related to patients' pre-existing conditions, predominantly among people aged 70 years or older. Only ten of the reported fatalities (0.1 per 100,000 persons vaccinated) were assessed as consistent with a causal association to COVID-19 vaccination.

Conclusions: Adverse drug reactions with fatal outcomes after COVID-19 vaccines in Sweden were very rare. No new safety concerns were observed in this study.

Background: During the COVID-19 vaccination campaign in Sweden, pulmonary embolism (PE) was a frequently reported suspected serious adverse drug reaction. The aim was to estimate risk of PE following vaccination for COVID-19 in the Swedish population aged 18 to 84 years.

Methods: Population-based cohort study using the CoVacSafe-SE established platform including national registers. PE-case definition: Individuals discharged from inpatient-care or visiting specialized outpatient-care with a main diagnosis of PE occurring between 27-Dec-2020 and 31-Dec-2022 without simultaneous diagnosis of COVID-19 infection. Time-to-event analysis was performed using multi-variable Cox' proportional hazard's models. Hazard Ratios (HR) adjusted for age, sex and co-morbidities were modelled. The vaccines were BNT162b2/Comirnaty (R), mRNA1273/Spikevax (R) and ChAdOx1 nCoV-19/Vaxzevria (R) without regard to variants. Doses number one to five were studied.

Results: Eighty percent of the study-population (approximate to 6.1 million people) received at least two doses of COVID-19 vaccine. A total of 12,456 cases of PE were identified. Twenty-eight days after vaccinations we observed 99 cases after 701,455 1st doses of ChAdOx1 nCoV-19, HRadj, 1.29 (95%-CI, 1.05-1.59). Corresponding for BNT162b2 was 361 cases after 4,708,284 1st doses of BNT162b2 HR adj of 1.19 (95%-CI, 1.06-1.34) driven by age group 65-84; HR adj, 1.24 (95%-CI, 1.07-1.44). No increased risks were observed for mRNA1273.

Conclusion: In this nation-wide study, no strong associations were found between COVID-19 vaccinations and pulmonary embolism. Small increases in relative risk for the earliest doses of vaccines may be associated with prioritizing the frailest groups of people in the vaccination campaign, thus selection bias or unmeasured residual confounding is possible.

Background

Gonadotropin-releasing hormone agonists (GnRH) used in prostate cancer (PCa) are associated with atherogenic dyslipidaemia. It can be assumed that GnRH need to be used with greater caution in men with type 2 diabetes mellitus (T2DM). This study investigated association of GnRH with atherogenic lipids (AL) in PCa men with T2DM.

Methods

Two cohorts including 38,311 men with 11 years follow-up based on Swedish national registers were defined (PCa-Exposure cohort and GnRH-Exposure cohort). Based on European guidelines on cardiovascular diseases (CVD), primary outcomes were defined as: 1.0 mmol/L increase in AL and lipid-lowering therapy (LLT) intensification. We used Cox proportional-hazards models and Kaplan–Meier curves to assess the association.

Results

There was an association between GnRH and increased AL (i.e., triglyceride, PCa-Exposure cohort: HR 1.77, 95% CI 1.48–2.10; GnRH-Exposure cohort: HR 1.88, 95% CI 1.38–2.57). There was also an association between PCa diagnosis and increased AL. In contrast, no association between LLT intensification and GnRH was found.

Conclusion

In this large population-based study, men with T2DM on GnRH for PCa had an increased risk of increased atherogenic lipids. These results highlight the need to closely monitor lipids and to be ready to intensify lipid-lowering therapy in men with T2DM on GnRH for PCa.

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10^-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.

Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10^-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.