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Background There have been concerns about COVID-19 vaccination safety among frail older individuals. We investigated the relationship between COVID-19 mRNA vaccination and mortality among individuals aged ≥ 70 years and whether mortality varies across four groups of health services used. Methods In this nationwide cohort study, we included 688,152 individuals aged ≥ 70 years at the start of the Norwegian vaccination campaign (December 27, 2020). We collected individual-level data from the Norwegian Emergency Preparedness Register for COVID-19. Vaccinated and unvaccinated individuals were matched (1:1 ratio) on the date of vaccination based on sociodemographic and clinical characteristics. The main outcome was all-cause mortality during 21 days after first dose of COVID-19 mRNA vaccination. Kaplan-Meier survival functions were estimated for the vaccinated and unvaccinated groups. We used Cox proportional-hazards regression to estimate hazard ratios (HRs) of death between vaccinated and unvaccinated individuals, with associated 95% confidence intervals (CIs), overall and by use of health services (none, home-based, short- and long-term nursing homes) and age group. Results Between December 27, 2020, and March 31, 2021, 420,771 older individuals (61.1%) were vaccinated against COVID-19. The Kaplan-Meier estimates based on the matched study sample showed a small absolute risk difference in all-cause mortality between vaccinated and unvaccinated individuals, with a lower mortality in the vaccinated group (overall HR 0.28 [95% CI: 0.24–0.31]). Similar results were obtained in analyses stratified by use of health services and age group. Conclusion We found no evidence of increased short-term mortality among vaccinated individuals in the older population after matching on sociodemographic and clinical characteristics affecting vaccination and mortality. publishedVersion

Background: Whether the SARS-CoV-2 mRNA vaccines may cause a transient increased stroke risk is uncertain. Methods: In a registry-based cohort of all adult residents at December 27, 2020, in Norway, we linked individual-level data on COVID-19 vaccination, positive SARS-CoV-2 test, hospital admissions, cause of death, health care worker status, and nursing home resident status extracted from the Emergency Preparedness Register for COVID-19 in Norway. The cohort was followed for incident intracerebral bleeding, ischemic stroke, and subarachnoid hemorrhage within the first 28 days after the first/second or third dose of mRNA vaccination until January 24, 2022. Stroke risk after vaccination relative to time not exposed to vaccination was assessed by Cox proportional hazard ratio, adjusted for age, sex, risk groups, health care personnel, and nursing home resident. Results: The cohort included 4 139 888 people, 49.8% women, and 6.7% were ≥80 years of age. During the first 28 days after an mRNA vaccine, 2104 people experienced a stroke (82% ischemic stroke, 13% intracerebral hemorrhage, and 5% subarachnoid hemorrhage). Adjusted hazard ratios (95% CI) after the first/second and after the third mRNA vaccine doses were 0.92 (0.85–1.00) and 0.89 (0.73–1.08) for ischemic stroke, 0.81 (0.67–0.98) and 1.05 (0.64–1.71) for intracerebral hemorrhage, and 0.64 (0.46–0.87) and 1.12 (0.57–2.19) for subarachnoid hemorrhage, respectively. Conclusions: We did not find increased risk of stroke during the first 28 days after an mRNA SARS-CoV-2 vaccine.

ImportanceThe SARS-CoV-2 mRNA vaccines are associated with an increased risk of myocarditis. This association appears to be strongest in male adolescents and younger males and after the second dose. Few studies have evaluated the association after booster doses.ObjectiveTo evaluate the risk of myocarditis following SARS-CoV-2 mRNA booster vaccination in 12-to-39-year-olds.DesignA multinational cohort study using nationwide register data.SettingDenmark, Finland, Norway, and Sweden.ParticipantsCohorts comprising all 8.9 million individuals residing in each of the four countries, born 1982-2009, and alive at start of study on December 27, 2020, without a previous diagnosis of myocarditis or pericarditis or laboratory-confirmed SARS-CoV-2 infection.ExposuresThe 28-day acute risk periods following the second and third dose of BNT162b2 and mRNA-1273, respectively, in a homologous schedule defines the exposures of interest.Main Outcomes and MeasuresCohort participants were followed until an inpatient diagnosis of myocarditis, loss to follow-up, or end of study (latest data availability in each country), whichever occurred first. In each of the four countries, Poisson regression was used to estimate adjusted incidence rate ratios (IRRs) of myocarditis, with associated 95% confidence intervals (CIs), according to vaccination status. Country-specific results were combined in meta-analyses.ResultsA total of 8.9 million residents were followed for 12,271,861 person-years. We identified 1533 cases of myocarditis. In 12-to-39-year-old males, the 28-day acute risk period following the third dose of BNT162b2 or mRNA-1273 was associated with an increased incidence rate of myocarditis compared to the post-acute risk period 28 days or more after a second homologous dose (IRR, 2.08 [95% CI, 1.31 to 3.33] and 8.89 [95% CI, 2.26 to 35.03], respectively). The corresponding incidence rates following the third dose of BNT162b2 and mRNA-1273 were 0.86 and 1.95, respectively, within 28 days of follow-up among 100,000 individuals.Conclusions and RelevanceOur results suggest that a booster dose is associated with increased myocarditis risk in male adolescents and young male adults.KEY POINTSQuestionIs a first booster dose of SARS-CoV-2 messenger RNA (mRNA) vaccine associated with increased risk of myocarditis in male adolescents and young male adults?FindingsIn a cohort study of 8.9 million residents in Denmark, Finland, Norway, and Sweden, a booster dose of BNT162b2 or mRNA-1273 vaccine was associated with increased risk of myocarditis in 12-to-39-year-old males, with incidence rates 0.86 and 1.95, respectively, within 28 days of follow-up per 100,000 vaccinated individuals.MeaningA booster dose with a SARS-CoV-2 mRNA vaccine is associated with increased myocarditis risk in male adolescents and young male adults. Compared to after a primary course, the risk appears attenuated.

The Norwegian Institute of Public Health's statistics on immunisation against SARS-CoV-2 show that vaccination coverage for foreign-born persons living in Norway is lower than for persons born in Norway. As of January 2022, the difference was 18 percentage points (76 % versus 94 %). This difference is likely to be due to several factors, one of which may be that many of those who were immunised abroad have not had this registered in the Norwegian Immunisation Registry.In November 2021, the Norwegian Institute of Public Health conducted a public health survey in the county of Viken. Respondents were asked if they had been vaccinated against the coronavirus, if they were vaccinated in Norway or abroad, and if immunisation abroad had been reported to the Norwegian health service. They were also asked to specify their country of birth. The sample was drawn from the National Population Register. The survey was conducted online and the response rate was 41 % (n = 108 738).A total of 105 010 (97 %) of the respondents had had at least one dose of the coronavirus vaccine. Of these, 724 (1 %) had only been vaccinated abroad. This applied to 392 (3 %) of the 13 286 foreign-born persons, 203 (52 %) of whom had reported their immunisation to the Norwegian health service.In this dataset, unregistered immunisation abroad explains only a small proportion of the difference in vaccination coverage between Norwegian-born and foreign-born persons.

Summary Background Diabetes prevalence is increasing in most places in the world, but prevalence is affected by both risk of developing diabetes and survival of those with diabetes. Diabetes incidence is a better metric to understand the trends in population risk of diabetes. Using a multicountry analysis, we aimed to ascertain whether the incidence of clinically diagnosed diabetes has changed over time. Methods In this multicountry data analysis, we assembled aggregated data describing trends in diagnosed total or type 2 diabetes incidence from 24 population-based data sources in 21 countries or jurisdictions. Data were from administrative sources, health insurance records, registries, and a health survey. We modelled incidence rates with Poisson regression, using age and calendar time (1995–2018) as variables, describing the effects with restricted cubic splines with six knots for age and calendar time. Findings Our data included about 22 million diabetes diagnoses from 5 billion person-years of follow-up. Data were from 19 high-income and two middle-income countries or jurisdictions. 23 data sources had data from 2010 onwards, among which 19 had a downward or stable trend, with an annual estimated change in incidence ranging from −1·1% to −10·8%. Among the four data sources with an increasing trend from 2010 onwards, the annual estimated change ranged from 0·9% to 5·6%. The findings were robust to sensitivity analyses excluding data sources in which the data quality was lower and were consistent in analyses stratified by different diabetes definitions. Interpretation The incidence of diagnosed diabetes is stabilising or declining in many high-income countries. The reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources. Funding US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Aims/hypothesis Obesity and insulin resistance may be associated with elevated plasma concentration of branched-chain amino acids (BCAAs) and impaired BCAA metabolism. However, it is unknown whether the insulin-sensitising effect of long-term exercise can be explained by concomitant change in BCAAs and their metabolism. Methods We included 26 sedentary overweight and normal-weight middle-aged men from the MyoGlu clinical trial, with or without dysglycaemia, for 12 weeks of supervised intensive exercise intervention, including two endurance and two resistance sessions weekly. Insulin sensitivity was measured as the glucose infusion rate (GIR) from a hyperinsulinaemic−euglycaemic clamp. In addition, maximum oxygen uptake, upper and lower body strength and adipose tissue depots (using MRI and spectroscopy) were measured, and subcutaneous white adipose tissue (ScWAT) and skeletal muscle (SkM) biopsies were harvested both before and after the 12 week intervention. In the present study we have measured plasma BCAAs and related metabolites using CG-MS/MS and HPLC-MS/MS, and performed global mRNA-sequencing pathway analysis on ScWAT and SkM. Results In MyoGlu, men with dysglycaemia displayed lower GIR, more fat mass and higher liver fat content than normoglycaemic men at baseline, and 12 weeks of exercise increased GIR, improved body composition and reduced liver fat content similarly for both groups. In our current study we observed higher plasma concentrations of BCAAs (14.4%, p = 0.01) and related metabolites, such as 3-hydroxyisobutyrate (19.4%, p = 0.034) in dysglycaemic vs normoglycaemic men at baseline. Baseline plasma BCAA levels correlated negatively to the change in GIR (ρ = −0.41, p = 0.037) and $$ \dot{V}{\mathrm{O}}_{2\max } $$ V ̇ O 2 max (ρ = −0.47, p = 0.015) after 12 weeks of exercise and positively to amounts of intraperitoneal fat (ρ = 0.40, p = 0.044) and liver fat (ρ = 0.58, p = 0.01). However, circulating BCAAs and related metabolites did not respond to 12 weeks of exercise, with the exception of isoleucine, which increased in normoglycaemic men (10 μmol/l, p = 0.01). Pathway analyses of mRNA-sequencing data implied reduced BCAA catabolism in both SkM and ScWAT in men with dysglycaemia compared with men with normoglycaemia at baseline. Gene expression levels related to BCAA metabolism correlated positively with GIR and markers of mitochondrial content in both SkM and ScWAT, and negatively with fat mass generally, and particularly with intraperitoneal fat mass. mRNA-sequencing pathway analysis also implied increased BCAA metabolism after 12 weeks of exercise in both groups and in both tissues, including enhanced expression of the gene encoding branched-chain α-ketoacid dehydrogenase (BCKDH) and reduced expression of the BCKDH phosphatase in both groups and tissues. Gene expression of SLC25A44, which encodes a mitochondrial BCAA transporter, was increased in SkM in both groups, and gene expression of BCKDK, which encodes BCKDH kinase, was reduced in ScWAT in dysglycaemic men. Mediation analyses indicated a pronounced effect of enhanced SkM (~53%, p = 0.022), and a moderate effect of enhanced ScWAT (~18%, p = 0.018) BCAA metabolism on improved insulin sensitivity after 12 weeks of exercise, based on mRNA sequencing. In comparison, plasma concentration of BCAAs did not mediate any effect in this regard. Conclusion/interpretation Plasma BCAA concentration was largely unresponsive to long-term exercise and unrelated to exercise-induced insulin sensitivity. On the other hand, the insulin-sensitising effect of long-term exercise in men may be explained by enhanced SkM and, to a lesser degree, also by enhanced ScWAT BCAA catabolism.

Background: Cardiovascular outcome trials have shown cardiovascular benefit with sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors have not shown an effect. We aimed to address knowledge gaps regarding the comparative effectiveness of SGLT2 inhibitor use in clinical practice (with DPP-4 inhibitor use as an active comparator) across a range of cardiovascular risks and in diverse geographical settings. Methods: In this comparative cohort study, we used data from clinical practice from 13 countries in the Asia-Pacific, Middle East, European, and North American regions to assess the risk of cardiovascular events and death in adult patients with type 2 diabetes newly initiated on SGLT2 inhibitors compared with those newly initiated on DPP-4 inhibitors. De-identified health records were used to select patients who were initiated on these drug classes between Dec 1, 2012, and May 1, 2016, with follow-up until Dec 31, 2014, to Nov 30, 2017 (full range; dates varied by country). Non-parsimonious propensity scores for SGLT2 inhibitor initiation were developed for each country and patients who were initiated on an SGLT2 inhibitor were matched with those who were initiated on a DPP-4 inhibitor in a 1:1 ratio. Outcomes assessed were hospitalisation for heart failure, all-cause death, myocardial infarction, and stroke. Hazard ratios (HRs) were estimated by country and then pooled in a weighted meta-analysis. Findings: Following propensity score matching, 193 124 new users of SGLT2 inhibitors and 193 124 new users of DPP-4 inhibitors were included in the study population. Participants had a mean age of 58 years (SD 12·2), 170 335 (44·1%) of 386 248 were women, and 111 933 (30·1%) of 372 262 had established cardiovascular disease. Initiation of an SGLT2 inhibitor versus a DPP-4 inhibitor was associated with substantially lower risks of hospitalisation for heart failure (HR 0·69, 95% CI 0·61–0·77; p

Importance: Reports of myocarditis after SARS-CoV-2 messenger RNA (mRNA) vaccination have emerged. Objective: To evaluate the risks of myocarditis and pericarditis following SARS-CoV-2 vaccination by vaccine product, vaccination dose number, sex, and age. Design, Setting, and Participants: Four cohort studies were conducted according to a common protocol, and the results were combined using meta-analysis. Participants were 23122522 residents aged 12 years or older. They were followed up from December 27, 2020, until incident myocarditis or pericarditis, censoring, or study end (October 5, 2021). Data on SARS-CoV-2 vaccinations, hospital diagnoses of myocarditis or pericarditis, and covariates for the participants were obtained from linked nationwide health registers in Denmark, Finland, Norway, and Sweden. Exposures: The 28-day risk periods after administration date of the first and second doses of a SARS-CoV-2 vaccine, including BNT162b2, mRNA-1273, and AZD1222 or combinations thereof. A homologous schedule was defined as receiving the same vaccine type for doses 1 and 2. Main Outcomes and Measures: Incident outcome events were defined as the date of first inpatient hospital admission based on primary or secondary discharge diagnosis for myocarditis or pericarditis from December 27, 2020, onward. Secondary outcome was myocarditis or pericarditis combined from either inpatient or outpatient hospital care. Poisson regression yielded adjusted incidence rate ratios (IRRs) and excess rates with 95% CIs, comparing rates of myocarditis or pericarditis in the 28-day period following vaccination with rates among unvaccinated individuals. Results: Among 23122522 Nordic residents (81% vaccinated by study end; 50.2% female), 1077 incident myocarditis events and 1149 incident pericarditis events were identified. Within the 28-day period, for males and females 12 years or older combined who received a homologous schedule, the second dose was associated with higher risk of myocarditis, with adjusted IRRs of 1.75 (95% CI, 1.43-2.14) for BNT162b2 and 6.57 (95% CI, 4.64-9.28) for mRNA-1273. Among males 16 to 24 years of age, adjusted IRRs were 5.31 (95% CI, 3.68-7.68) for a second dose of BNT162b2 and 13.83 (95% CI, 8.08-23.68) for a second dose of mRNA-1273, and numbers of excess events were 5.55 (95% CI, 3.70-7.39) events per 100000 vaccinees after the second dose of BNT162b2 and 18.39 (9.05-27.72) events per 100000 vaccinees after the second dose of mRNA-1273. Estimates for pericarditis were similar. Conclusions and Relevance: Results of this large cohort study indicated that both first and second doses of mRNA vaccines were associated with increased risk of myocarditis and pericarditis. For individuals receiving 2 doses of the same vaccine, risk of myocarditis was highest among young males (aged 16-24 years) after the second dose. These findings are compatible with between 4 and 7 excess events in 28 days per 100000 vaccinees after BNT162b2, and between 9 and 28 excess events per 100000 vaccinees after mRNA-1273. This risk should be balanced against the benefits of protecting against severe COVID-19 disease.

Aims We investigated the current extent of undiagnosed diabetes and prediabetes and their associated cardiovascular risk profile in a population-based study. Methods All residents aged ≥20 years in the Nord-Trøndelag region, Norway, were invited to the HUNT4 Survey in 2017–2019, and 54% attended. Diagnosed diabetes was self-reported, and in those reporting no diabetes HbA1c was used to classify undiagnosed diabetes (≥48 mmol/mol [6.5%]) and prediabetes (39–47 mmol/mol [5.7%–6.4%]). We estimated the age- and sex-standardized prevalence of these conditions and their age- and sex-adjusted associations with other cardiovascular risk factors. Results Among 52,856 participants, the prevalence of diabetes was 6.0% (95% CI 5.8, 6.2), of which 11.1% were previously undiagnosed (95% CI 10.1, 12.2). The prevalence of prediabetes was 6.4% (95% CI 6.2, 6.6). Among participants with undiagnosed diabetes, 58% had HbA1c of 48–53 mmol/mol (6.5%–7.0%), and only 14% (i.e., 0.1% of the total study population) had HbA1c >64 mmol/mol (8.0%). Compared with normoglycaemic participants, those with undiagnosed diabetes or prediabetes had higher body mass index, waist circumference, systolic blood pressure, triglycerides and C-reactive protein but lower low-density lipoprotein cholesterol (all p < 0.001). Participants with undiagnosed diabetes had less favourable values for every measured risk factor compared with those with diagnosed diabetes. Conclusions The low prevalence of undiagnosed diabetes suggests that the current case-finding-based diagnostic practice is well-functioning. Few participants with undiagnosed diabetes had very high HbA1c levels indicating severe hyperglycaemia. Nonetheless, participants with undiagnosed diabetes had a poorer cardiovascular risk profile compared with participants with known or no diabetes.

ObjectiveThe effects of levothyroxine (LT4)/liothyronine (LT3) combination therapy on quality of life (QoL) in hypothyroid patients former on LT4 monotherapy have been disappointing. We therefore wanted to test the effects of LT3 monotherapy on QoL in hypothyroid patients with residual symptoms despite thyroid stimulating hormone (TSH) values within the reference range.DesignFemale hypothyroid patients with residual symptoms on LT4 monotherapy or combination LT4/LT3 therapy received LT3 and LT4 monotherapy, respectively for 12 weeks in a non-blinded randomized crossover study.MethodsFifty-nine patients aged 18-65 years were included. QoL was assessed using one disease-specific questionnaire (ThyPRO) and two generic questionnaires (Fatigue Questionnaire and SF-36) at baseline and at the end of the two treatment periods. Clinical indices of cardiovascular health (resting heart rate and blood pressure), as well as thyroid tests, were assessed at baseline and at the end of the two treatment periods.ResultsAfter 12 weeks of LT3 treatment, 12 of the 13 domains of the ThyPRO questionnaire (physical, mental and social domains) showed significant improvements. The most pronounced improvements were less tiredness (mean -21 ± 26; PPPPConclusionsLT3 treatment improved QoL in women with residual hypothyroid symptoms on LT4 monotherapy or LT4/LT3 combination therapy. Short-term LT3 treatment did not induce biochemical or clinical hyperthyroidism, and no cardiovascular adverse effects were recorded. Further studies are needed to assess the long-term safety and efficacy of LT3 monotherapy.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03627611.

ObjectiveTo determine risk factors for SARS-CoV-2 infection and hospitalisation among children and adolescents.DesignNationwide, population-based cohort study. Setting: Norway from 1 March 2020 to 31 April 2021. Participants: All Norwegian residents Main outcome measuresPopulation-based health care and population registries were used to study risk factors for SARS-CoV-2 infection, including socioeconomic factors, country of origin, and pre-existing chronic comorbidities. All residents were followed until age 18, emigration, death, or end of follow-up. Hazard ratios (HR) estimated by Cox regression models were adjusted for testing frequency. Further, risk factors for admission to the hospital among the infected were investigated.ResultsOf 1 182 796 residents, 22608 (1.9%) tested positive by polymerase chain reaction or lateral flow tests, of whom 107 (0.5%) were admitted to a hospital. Low family income (aHR 1.40, 95% confidence interval 1.36 to 1.46), crowded housing (1.35, 1.30 to 1.39), household size, age, and area of living were independent risk factors for infection. A non-Nordic country of origin was the strongest risk factor (aHR 2.37, 95% CI 2.30 to 2.49), whereas chronic comorbidity was not associated with the risk of infection. Chronic comorbidity was associated with hospitalisation (aHR 4.15, 2.63 to 6.56), in addition to age, whereas socioeconomic status and country of origin did not predict hospitalisation among those infected.ConclusionsSocioeconomic factors, country of origin, and area of living were associated with the risk of SARS-CoV-2 infection. However, these factors did not predict hospitalisation among those infected. Chronic comorbidity was associated with the risk of admission but not with the overall risk of acquiring SARS-CoV-2.What is already known on this topicHospital admissions rates for covid-19 among children and adolescents are low compared to adults. Admission rates to hospitals and intensive care units for covid-19 have been higher in minority groups and in children and adolescents with chronic comorbidity.Whether underlying differences in susceptibility for severe disease or the incidence of infections are driving these associations have not been investigated.What this study addsLow family income, crowded housing and household size, and country of origin outside the Nordic countries were associated with increased risk of infection with SARS-CoV-2.None of these factors, but chronic comorbidities, were associated with the risk of hospital admission among those infected.

Aims The type 2 diabetes risk following gestational diabetes mellitus (GDM) is high, particularly among South Asian women in Western countries. Our study aimed to advance the knowledge regarding the mechanisms behind suboptimal follow-up in the Nordic and South Asian women with previous GDM by comparing: 1) their experiences, 2) health and disease perceptions, and 3) barriers to and facilitators of health-promoting behaviours. Methods This qualitative study was conducted in three hospital outpatient clinics in Norway, comprising 6 focus group interviews with 28 women 1-3 years after a pregnancy with GDM. The participants were purposively sampled and grouped according to their ethnicity. The data were analysed using thematic analysis, and a theoretical approach was applied to support the analysis and discuss the study's findings. Results Five main themes were identified: lack of resilience, emotional distress, 'caught between a rock and a hard place', postpartum abandonment, and insufficient guidance. The key determinants of the maintenance of unwanted health behaviours after GDM were consistent across the ethnic groups. Although the importance of a culturally sensitive approach was emphasised, it appeared secondary to the need for a more organised public healthcare during and after GDM. Conclusions Women's real-life constraints, combined with the inadequate healthcare-service implementation, could explain the non-adherence to the lifestyle-changes guidelines essential for preventing diabetes post-GDM. We suggest promoting specific coping strategies and changing the healthcare service approach rather than relying on women's capacity to initiate the necessary changes.

Objective To assess rates of cardiovascular and haemostatic events in the first 28 days after vaccination with the Oxford-AstraZeneca vaccine ChAdOx1-S in Denmark and Norway and to compare them with rates observed in the general populations. Design Population based cohort study. Setting Nationwide healthcare registers in Denmark and Norway. Participants All people aged 18-65 years who received a first vaccination with ChAdOx1-S from 9 February 2021 to 11 March 2021. The general populations of Denmark (2016-18) and Norway (2018-19) served as comparator cohorts. Main outcome measures Observed 28 day rates of hospital contacts for incident arterial events, venous thromboembolism, thrombocytopenia/coagulation disorders, and bleeding among vaccinated people compared with expected rates, based on national age and sex specific background rates from the general populations of the two countries. Results The vaccinated cohorts comprised 148 792 people in Denmark (median age 45 years, 80% women) and 132 472 in Norway (median age 44 years, 78% women), who received their first dose of ChAdOx1-S. Among 281 264 people who received ChAdOx1-S, the standardised morbidity ratio for arterial events was 0.97 (95% confidence interval 0.77 to 1.20). 59 venous thromboembolic events were observed in the vaccinated cohort compared with 30 expected based on the incidence rates in the general population, corresponding to a standardised morbidity ratio of 1.97 (1.50 to 2.54) and 11 (5.6 to 17.0) excess events per 100 000 vaccinations. A higher than expected rate of cerebral venous thrombosis was observed: standardised morbidity ratio 20.25 (8.14 to 41.73); an excess of 2.5 (0.9 to 5.2) events per 100 000 vaccinations. The standardised morbidity ratio for any thrombocytopenia/coagulation disorders was 1.52 (0.97 to 2.25) and for any bleeding was 1.23 (0.97 to 1.55). 15 deaths were observed in the vaccine cohort compared with 44 expected. Conclusions Among recipients of ChAdOx1-S, increased rates of venous thromboembolic events, including cerebral venous thrombosis, were observed. For the remaining safety outcomes, results were largely reassuring, with slightly higher rates of thrombocytopenia/coagulation disorders and bleeding, which could be influenced by increased surveillance of vaccine recipients. The absolute risks of venous thromboembolic events were, however, small, and the findings should be interpreted in the light of the proven beneficial effects of the vaccine, the context of the given country, and the limitations to the generalisability of the study findings.

Type 1 and type 2 diabetes mellitus incur an increased risk of fracture, with a generally higher risk among individuals with type 1 diabetes. The fracture risk among individuals with latent autoimmune diabetes of adulthood (LADA) is not known. The present cohort study aimed to estimate the risk of hip and forearm fracture among individuals with LADA, alongside type 1 and type 2 diabetes, using data from the second survey of the Trondelag Health Study (HUNT2) in 1995–97. All inhabitants aged 20 years or older (N = 92,936) were invited to attend, of whom 65,234 (70%) participated. A total of 1972 (3%) reported to have diabetes; 1399 were found to have type 2 diabetes, 144 to have LADA, and 138 to have type 1 diabetes. All participants were followed prospectively with respect to hip- and forearm fractures by linkage to the local fracture registry. During a median follow-up of 16.2 years, 2695 persons with hip fractures and 3533 persons with forearm fractures were identified. There was an increased risk of hip fracture in women with type 2 diabetes (HR = 1.51, 95% CI 1.24–1.85) and LADA (HR = 2.15, 95% CI 1.25–3.72), whereas women with type 1 diabetes did not have a significantly increased risk (HR = 2.13, 95% CI 0.89–5.14). Among men, only LADA was associated with an increased risk of hip fracture (HR = 2.69, 95% CI 1.34–5.41). There was no statistically significant association between any of the diabetes types and forearm fracture. In women with type 2 diabetes, the highest risks of hip fracture were observed among those with highest HbA1c level at baseline, longest time since diagnosis, and most visual and movement impairment. We found that individuals with LADA had an increased risk of hip fracture similar to that previously reported for individuals with type 1 diabetes, and no increased risk of forearm fracture.

Advanced age is the most important risk factor for death as a result of COVID-19, but there is a dearth of knowledge regarding the impact of chronic diseases. Using health registry data, we describe the disease profiles of persons who died after a confirmed infection with SARS-CoV-2 during the first three months of the pandemic in Norway.Data from the specialist health service (Norwegian Patient Registry, NPR) and the primary health service (Norwegian Registry for Primary Health Care, NRPHC) were linked to information on positive tests for SARS-CoV-2 from the Norwegian Surveillance System for Communicable Diseases (MSIS) and on deaths from the National Population Register. The data retrieval included the Norwegian population as of 1 March 2020 with data for confirmed infections, hospitalisations and deaths until 31 May 2020.Of 8 412 persons with a confirmed SARS-CoV-2 infection, altogether 244 (2.9 %) died, whereof 133 (55 %) were men. Among those with a confirmed infection, the proportion who died varied from 0.2 % (age60 years) to 52 % (age ≥ 90 years). Altogether 92 (38 %) patients died in hospital. 25 (16 %) of those who died elsewhere had previously been hospitalised for COVID-19. The proportion with no registered chronic disease was 39 % in the age group70 years and 26 % in the age group ≥ 70 years. The disease distribution varied between those patients who had died in and outside of hospital, especially for diagnoses of diabetes, renal failure and dementia.Among those who had a SARS-CoV-2 infection confirmed during the first three months of the pandemic in Norway, only a small proportion died. The majority of those who died were 70 years or older and had at least one chronic disease, but the disease profile varied between patients who died in and outside of hospital. Health registry data can help provide a better overview of and advice to risk groups in the population during an ongoing pandemic.

Cardiovascular diseases, cancer, type-2 diabetes and chronic obstructive pulmonary disease (COPD) were initially noted as the most common diseases among individuals who were hospitalised for COVID-19. However, the evidence base is weak. The objective of this study is to describe how selected diseases were distributed among adults with confirmed COVID-19 (COVID-19 positive tests) and among those hospitalised for COVID-19 compared to the general population.We used data from the Norwegian Patient Registry, the Norwegian Registry for Primary Health Care and the Norwegian Surveillance System for Communicable Diseases for adults from the age of 20 and older for the period 1 March 2020-13 May 2020.Of all those who tested positive for COVID-19, 7 632 (94 %) were aged 20 years or older, and 1 025 (13.4 %) of these had been hospitalised. Among those hospitalised with COVID-19, there was a higher proportion of individuals with cardiovascular diseases (18.3 % versus 15.6 %), cancer (6.9 % versus 5.4 %), type-2 diabetes (8.6 % versus 5.2 %) and COPD (3.8 % versus 2.7 %) than in the general population as a whole after adjusting for age. The proportion of hospitalised patients with asthma, other chronic respiratory disease, cardiovascular disease, ongoing cancer treatment, complications related to hypertension, obesity and overweight, neurological disorders and cardiac and renal failure was also higher than in the general population. There were few differences between persons who had tested positive for COVID-19 and the general population in terms of underlying conditions.Among those hospitalised for COVID-19, there was a higher proportion of patients with underlying illnesses than in the general population. This may indicate that these patients tend to have a more severe course of disease or that they are more likely to be hospitalised compared to healthy individuals. The results must be interpreted with caution, since the sample of COVID-19 individuals is non-random.

Children and adolescents are at lower risk of disease caused by SARS-CoV-2. We describe the incidence of confirmed infection and hospitalisation of children and adolescents under the age of 20 in Norway, and specifically among those with underlying conditions.The Norwegian Directorate of Health has collaborated with the Norwegian Institute of Public Health on the establishment of a data extraction system to monitor the coronavirus outbreak. Data from the specialist health service (Norwegian Patient Registry, NPR), and the primary health service (Norwegian Registry for Primary Health Care, NRPHC) are linked to data on positive SARS-CoV-2 tests from the Surveillance System for Communicable Diseases (MSIS). This covers all persons living in Norway as of 1 March 2020, with data on confirmed infection up to and including 13 May 2020 and on hospitalisations up to and including 30 April 2020.Of 8 125 persons with confirmed SARS-CoV-2 in the whole population, 493 (6.1 %) were under 20 years old. The median age of the under-20s was 15 years, and 252 (51 %) were girls. 3 % were hospitalised. No deaths were registered among patients aged under 20 in Norway. We found a somewhat larger share with confirmed SARS-CoV-2 in the group with diseases of the neuromuscular system.Few children and adolescents have had SARS-CoV-2 confirmed, and only a very few have been hospitalised. Underlying conditions may result in a lower threshold for testing, and hence a higher incidence of confirmed infection in this group, although higher risk cannot be excluded.

Background and Aims Hypomagnesaemia has been associated with increased insulin resistance and decreased insulin secretion. Recent data suggest that early post-engraftment hypomagnesaemia may play a role in development of post-transplant diabetes mellitus (PTDM). This single-centre study investigated the association between hypomagnesaemia 8 weeks post-engraftment and glucose metabolism changes 1 year after kidney transplantation. Method The study included 425 renal transplantation recipients, transplanted at Oslo University Hospital between March 2015 and May 2018. All included patients had functioning grafts with valid blood sampling and oral glucose tolerance tests 8 weeks and 1 year after transplantation. Patients with known pretransplant diabetes and those developing PTDM the first 8 weeks after transplantation were excluded. The association between plasma magnesium 8 weeks after transplantation and HbA1c, fasting plasma glucose and 2-hr glucose after 1 year was tested using both unadjusted and multiple linear regression, adjusted for: gender, age, body mass index (BMI), systolic blood pressure (SBP), tacrolimus (trough), measured glomerular filtration rate (mGFR; iohexol clearance) and plasma triglycerides. Results Patients had a median age of 54 (range 18-83) years, 65% were men and mean mGFR 1 year after transplantation was 56 (SD±14) ml/min/1.73m2. Median plasma magnesium was 0.72 (0.46-0.94) mmol/L 8 weeks after Tx and patients with hypomagnesaemia (Mg< 0.7 mmol/L) (n=169) were not different compared to patients with normal plasma magnesium (n=256) regarding age, gender, BMI, tacrolimus, mGFR, SBP or plasma triglycerides after 1 year. In unadjusted linear regression 1 mmol/L higher plasma magnesium at 8 weeks was associated with the following glycaemic endpoints 1 year after transplantation (β-coefficient, CI 95%, p-value); fasting glucose: HbA1c: +9 mmol/mol (1;16, P=0.02); +0.5 mmol/L (-0.7;1.7, P=0.39); 2-hour glucose: +0.74 mmol/L (-2.5;3.9, P=0.65). In multiple linear regression the following numbers were: Fasting glucose: HbA1c: +8 mmol/mol (0.3;16, P=0.042); +0.7 mmol/L (-0.5;2.0, P=0.26); 2-hour glucose: +2.8 mmol/L (-0.6;6.2, P=0.11). Conclusion In both unadjusted and multiple linear regression there was a positive correlation between 8-week plasma magnesium and HbA1c 1 year after transplantation. A similar trend was found for fasting and 2-hour glucose, although this was not statistically significant.

Plasma concentration of branched-chain amino acids (BCAAs) is associated with insulin resistance. However, it is unknown if the insulin sensitizing effect of exercise can be explained by BCAAs. In agreement with previous reports, we found that plasma BCAAs concentration was higher, and transcription of BCAA catabolic enzymes in skeletal muscle (SkM) and subcutaneous white adipose tissue (ScWAT) was lower in dysglycemic (DG) than normoglycemic (NG) men. Twelve weeks of intensive exercise enhanced insulin sensitivity by ~40% in both groups, as quantified by euglycemic hyperinsulinemic clamp, but no changes were observed in plasma BCAAs concentrations. However, pathway analyses of mRNA sequencing data predicted enhanced BCAA catabolism in both SkM and ScWAT, which mediated the effect of exercise on insulin sensitivity. Our results suggest that the insulin sensitizing effect of exercise cannot be explained by plasma BCAAs, but imply that tissue catabolism of BCAAs may be linked to regulation of insulin sensitivity.

Background Randomized trials demonstrated a lower risk of cardiovascular (CV) events with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) in patients with type 2 diabetes (T2D) at high...

Background Prior studies found patients treated with sodium-glucose co-transporter-2 inhibitors (SGLT-2i) had lower rates of death and heart failure (HF). Whether the benefits of SGLT-2i vary based upon the presence of cardiovascular disease (CVD) is unknown. Objectives This study sought to determine the association between initiation of SGLT-2i therapy and HF or death in patients with and without CVD. Methods The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study was a multinational, observational study in which adults with type 2 diabetes were identified. Patients prescribed an SGLT-2i or other glucose-lowering drugs (GLDs) were matched based on a propensity score for initiation of an SGLT-2i. Hazard ratios (HRs) for the risk of death, HF, and HF or death in patients with and without established CVD were estimated for each country and pooled. Results After propensity score matching, 153,078 patients were included in each group. At baseline, 13% had established CVD. Compared with therapy using other GLDs, initiation of an SGLT-2i was associated with lower risk of death in patients with and without CVD (HR: 0.56; 95% confidence interval [CI]: 0.44 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.63, respectively). There were also associations between SGLT-2i and lower risk of HF (HR: 0.72; 95% CI: 0.63 to 0.82; and HR: 0.61; 95% CI: 0.48 to 0.78, respectively) and the composite of HF or death (HR: 0.63; 95% CI: 0.57 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.62, respectively) observed in patients with and without established CVD. Conclusions In this large, multinational, observational study, initiation of SGLT-2i was associated with lower risk of death and HF regardless of pre-existing CVD. Ongoing clinical trials will provide further evidence regarding the benefit of SGLT-2i in patients without established CVD. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614)

Background Roux-en-Y gastric bypass (RYGB) is a common surgical procedure for treatment of morbid obesity. RYGB induces considerable and sustained weight loss, and remission of obesity related-comorbidities. While studies have suggested negative effects of RYGB on bone health, long-term data are lacking. We aimed to evaluate the prevalence of aBMD below the expected range for age, osteopenia, osteoporosis and low-energy fractures in a defined patient cohort 10 years after RYGB. Secondly, we wanted to identify factors associated with increased risk of aBMD z-score or t-score of −1.1 or lower 10 years after RYGB. Methods Patients undergoing RYGB surgery from June 2004 to December 2006 at the Department of Morbid Obesity and Bariatric Surgery, Oslo University Hospital, a tertiary referral centre for treatment of morbid obesity, were invited to a 10 year follow-up. Follow-up visits included morning fasting blood samples, clinical examination, anthropometric measures and dual energy X-ray absorptiometry (DXA). Results Out of 194 patients eligible for the study, 124 attended the 10 year follow-up and 122 (63%) were examined with DXA. Mean (SD) age was 50.3 (9.0) years, 118 (97%) were of Caucasian ethnicity, 94 were females (77%), of whom 41 (44%) were postmenopausal. Secondary hyperparathyroidism (SHPT) was noted in 37 participants (31%) and vitamin D deficiency (value below 50 nmol/L) and insufficiency (value below 75 nmol/L) in 40 (33%) and 91 (75%), respectively. Among the 63 participants who were premenopausal females or males 49 years or younger the prevalence of areal bone mineral density (aBMD) in the lower range of normal (z-score −1.1- to −1.9) was 30% (n = 19) and aBMD below the expected range for age (z-score ≤ −2.0) was noted in 8% (n = 5). Among the 59 participants who were postmenopausal females or males 50 years or older, the prevalence of osteopenia (t-score −1.1 to −2.4) was 51% (n = 30) and osteoporosis (t-score ≤ −2.5) was 27% (n = 16). The bone resorption markers CTX-1 and PINP were higher in participants with aBMD z-score or t-score of −1.1 or lower compared to participants with aBMD z-score or t-score of −1.0 or higher. Preoperative hypothyroidism, or higher age, postmenopausal status, BMI

Background Obesity and type 2 diabetes (T2D) are associated with an increased risk of skeletal fractures despite a normal areal bone mineral density (aBMD) and low bone turnover, possibly due to reduced bone material strength. Roux-en-Y gastric bypass (RYGB) enables a substantial and persistent weight loss and resolution of obesity related comorbidities such as T2D. However, the procedure induces a decrease in aBMD and increased bone turnover and fracture rate. To our knowledge, changes in bone material strength after RYGB have not been explored. This study aimed to evaluate changes in factors influencing bone quality; bone material strength, aBMD and bone turnover markers, in a population with morbid obesity undergoing RYGB and whether these changes differed in participants with and without T2D. We also sought to assess factors associated with bone material strength and bone mineral density in obese subjects before and after RYGB. Methods We examined 34 participants before and one year after RYGB, of whom 13 had T2D. Bone material strength index (BMSi) was evaluated by impact microindentation, aBMD and body composition by Dual energy X-ray absorptiometry, levels of bone turnover markers and calciotropic hormones were estimated from fasting serum samples. Participants with and without T2D were comparable before surgery, with the exception of glycosylated hemoglobin (HbA1c). Results Preoperatively, BMSi was inversely associated with BMI, βunadjusted −1.1 (−1.9 to −0.28), R2 = 0.19, p = 0.010, and this association remained significant after adjusting for age and gender. After RYGB the participants had lost a mean ± SD of 33.9 ± 10.9 kg, 48.7 ± 14.2% of total body fat, increased physical activity, unchanged vitamin D levels, and all but one of the 13 participants with T2D were in diabetes remission. BMSi increased from 78.1 ± 8.5 preoperatively to 82.0 ± 6.4 one year after RYGB, corresponding to an increase of 4.0 ± 9.8 in absolute units or 6.3 ± 14.0%, p = 0.037. The increase was comparable in participants with and without T2D. In subjects with T2D, a larger decrease in HbA1c was associated with a larger increase in BMSi βunadjusted −9.2 (−16.5 to −1.9), R2 = 0.47, p = 0.019. Bone turnover markers (CTX-1 and PINP) increased by 195.1 ± 133.5% and 109.5 ± 70.6%, respectively. aBMD decreased by 3.9 ± 5.5% in the lumbar spine, 8.2 ± 4.6% in the femoral neck, 11.6 ± 4.9% in total hip and 9.4 ± 3.8% in total body. Conclusion Our findings indicate that bone material strength improves despite an increase in bone turnover and a decrease in aBMD one year after RYGB. Trends were statistically comparable in participants with and without T2D. However, improved glucose control was associated with improved bone material strength in participants with T2D.

The perilipin proteins enclose intracellular lipid droplets. We describe the mRNA expression of the five perilipins in human skeletal muscle in relation to fatty acid supply, exercise and energy balance. We observed that all perilipins were expressed in skeletal muscle biopsies with the highest mRNA levels of perilipin 2, 4 and 5. Cultured myotubes predominantly expressed perilipin 2 and 3. In vitro, incubation of myotubes with fatty acids enhanced mRNA expression of perilipin 1, 2 and 4. In vivo, low fat diet increased mRNA levels of perilipin 3 and 4. Endurance training, but not strength training, enhanced the expression of perilipin 2 and 3. Perilipin 1 mRNA correlated positively with body fat mass, whereas none of the perilipins were associated with insulin sensitivity. In conclusion, all perilipins mRNAs were expressed in human skeletal muscle. Diet as well as endurance exercise modulated the expression of perilipins.