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Background: The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is rapidly spreading worldwide. There is limited information about prognostic markers that could help clinicians to identify COVID-19 patients with a poor prognosis. Serum levels of the immune activation marker neopterin has shown to be of prognostic value in patients with SARS. The aim of this study was to investigate whether serum neopterin is associated with the severity of COVID-19.Methods: We included 34 patients with confirmed COVID-19 between March 3 and March 30, 2020. Fifteen patients had mild disease and did not require hospitalization, whereas 19 patients developed severe COVID-19 requiring intensive care. Concentrations of serum neopterin, tryptophan, and kynurenine were measured at and repeatedly after inclusion.Results: We found a more than two-fold higher mean concentration of neopterin in severely ill patients (mean value 42.0 nmol/L (SD 18.2)) compared to patients with mild symptoms (16.9 nmol/L (SD 11.0)). All of the severe cases had elevated neopterin concentrations (> 9.1 nmol/L) at the initial sampling with values ranging from 17.2 to 86.7 nmol/L. In comparison, 10 of 15 patients with mild disease had neopterin levels above 9.1 nmol/L, with concentrations in the range from 4.9 to 31.6 nmol/L. Neopterin levels gradually decreased during the course of COVID-19, but severe cases maintained elevated levels for a longer period. Moreover, lower levels of tryptophan and higher levels of kynurenine, indicating an increased tryptophan catabolism, were seen in the group with severe cases.Conclusions: In conclusion, we found that serum neopterin levels are associated with the severity of COVID-19. Our findings suggest that neopterin could be used as a prognostic marker, but further studies are needed to elucidate how it can be used in the clinic. [ABSTRACT FROM AUTHOR]

Background: Incidence rates of cardiomyopathies, which are a common cause of heart failure in young people, have increased during the last decades. An association between body weight in adolescence and future cardiomyopathy among men was recently identified. Whether or not this holds true also for women is unknown. The aim was therefore to determine whether for young women being overweight or obese is associated with a higher risk of developing cardiomyopathy.Methods: This was a registry-based national prospective cohort study with data collected from the Swedish Medical Birth Register, 1982 to 2014, with up to 33 years of follow-up. Included women were of childbearing age (18-45 years) during the initial antenatal visit in their first or second pregnancy (n=1 393 346). We obtained baseline data on body mass index (BMI), smoking, education, and previous disorders. After exclusions, mainly because of previous disorders, the final sample was composed of 1 388 571 women. Cardiomyopathy cases were identified by linking the Medical Birth Register to the National Patient and Cause of Death registers.Results: In total, we identified 1699 cases of cardiomyopathy (mean age at diagnosis, 46.2 [SD 9.1] years) during the follow-up with an incidence rate of 5.9 per 100 000 observation years. Of these, 481 were diagnosed with dilated cardiomyopathy, 246 had hypertrophic cardiomyopathy, 61 had alcohol/drug-induced cardiomyopathy, and 509 had other forms. The lowest risk for being diagnosed with a cardiomyopathy was detected at a BMI of 21 kg/m2, with a gradual increase in risk with higher BMI, particularly for dilated cardiomyopathy, where a hazard ratio of 4.71 (95% CI, 2.81-7.89) was found for severely obese subjects (BMI ≥35 kg/m2), as compared with BMI 20 to <22.5.Conclusions: Elevated BMI among young women was associated with an increased risk of being diagnosed with a subsequent cardiomyopathy, especially dilated cardiomyopathy, starting already at mildly elevated body weight, whereas severe obesity entailed an almost 5-fold increase in risk. With the increasing numbers of persons who are overweight or obese, higher rates of cardiomyopathy can be expected in the future, along with an altered disease burden related to adiposity. [ABSTRACT FROM AUTHOR]

Background Lyme borreliosis (LB) of the heart is called Lyme carditis (LC), which often manifests with high-grade atrioventricular block (AVB) requiring pacemaker implantation. LC is treated with antibiotics, and most patients recover fully after treatment. The overall incidence of LC, and of LC as a cause of pacemaker implantation, has not previously been systematically studied. Methods This was a case-control study based on data from Swedish national registers. The study was divided into two parts; part 1 including all patients diagnosed with AVB between 2001 and 2018, and part 2 including all patients who had received a pacemaker due to AVB between 2010 and 2018. Patients diagnosed with LB 90 days before and 180 days after the AVB diagnosis were identified among the patients and compared to matched control groups generated from the general population. Results Of 81 063 patients with AVB, 102 were diagnosed with LB. In the control group, 27 were diagnosed with LB. The yearly incidence of LC was 0.056 per 100 000 adults and year. Of 25 241 patients who had received a pacemaker for AVB, 31 were diagnosed with LB. In the control group, 8 were diagnosed with LB. The yearly incidence of LC as a cause of pacemaker implantation was 0.033 per 100 000 adults and year. The estimated risk for patients with LC to receive a permanent pacemaker was 59%. Conclusions LC is a rare cause of AVB. Nevertheless, more than half of patients with LC receive a permanent pacemaker for a condition that is easily cured with antibiotics. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: Modifiable lifestyle factors in relation to risk for cardiomyopathy, a common and increasing cause of heart failure in the young, have not been widely studied. We sought to investigate a potential link between obesity, a recognized predictor of early heart failure, in adolescence and being diagnosed with cardiomyopathy in adulthood. Methods: This was a nationwide register-based prospective cohort study of 1 668 893 adolescent men (mean age, 18.3 years; SD, 0.7 years) who enlisted for compulsory military service from 1969 to 2005. At baseline, body mass index (BMI), blood pressure, and medical disorders were registered, along with test results for fitness and muscle strength. Cardiomyopathy diagnoses were identified from the National Hospital Register and Cause of Death Register during an up to 46-year follow-up and divided into categories: dilated, hypertrophic, alcohol/drug-induced, and other. Hazard ratios were calculated with Cox proportional hazards models. Results: During follow-up (median, 27 years; Q1–Q3, 19–35 years), 4477 cases of cardiomyopathy were identified, of which 2631 (59%) were dilated, 673 (15%) were hypertrophic, and 480 (11%) were alcohol/drug-induced. Increasing BMI was strongly associated with elevated risk of cardiomyopathy, especially dilated, starting at levels considered normal (BMI, 22.5–<25 kg/m2; hazard ratio, 1.38 [95% CI, 1.22–1.57]), adjusted for age, year, center, and baseline comorbidities, and with a >8-fold increased risk at BMI ≥35 kg/m2 compared with BMI of 18.5 to <20 kg/m2. For each 1-unit increase in BMI, similarly adjusted hazard ratios were 1.15 (95% CI, 1.14–1.17) for dilated cardiomyopathy, 1.09 (95% CI, 1.06–1.12) for hypertrophic cardiomyopathy, and 1.10 (1.06–1.13) for alcohol/drug-induced cardiomyopathy. Conclusions: Even mildly elevated body weight in late adolescence may contribute to being diagnosed with cardiomyopathy in adulthood. The already marked importance of weight control in youth is further strengthened by these findings, as well as greater evidence for obesity as a potential important cause of adverse cardiac remodeling that is independent of clinically evident ischemic heart disease. [ABSTRACT FROM AUTHOR]

Aim To investigate the association of resting heart rate (RHR) measured in late adolescence with the long term risk of myocardial infarction (MI), ischemic stroke (IS), heart failure (HF), atrial fibrillation (AF), cardiovascular- and all-cause death. Methods and results We followed a cohort of Swedish men enrolled for conscription in 1968–2005 (n = 1,008,485; mean age = 18.3 years) until December 2014. Outcomes were collected from the national inpatient - (IPR), outpatient - (OPR) and cause of death registries. Cox proportional hazard models were used to analyze the longitudinal association between RHR and outcomes while adjusting for potential confounders. While we found no independent association between RHR and risk of IS or MI when comparing the highest with the lowest quintile of the RHR distribution, but a positive association persisted between RHR and incident HF (Hazard ratio (HR) = 1.39 [95% confidence interval (CI) = 1.29–1.49]) after adjustment for body mass index (BMI) and blood pressure (BP). In similarly adjusted models, an inverse association was found for AF while there were weaker associations with death from cardiovascular disease (CVD) and all causes (adjusted HR = 1.12 [CI = 1.04–1.21] and 1.20 [CI = 1.17–1.24]). After further adjustment for cardiorespiratory fitness (CRF), the associations persisted for HF (HR = 1.26 [1.17–1.35] for any diagnostic position and HR = 1.43 [1.28–1.60] for HF as a main diagnosis) and for all-cause death (HR 1.09 [1.05–1.12]) but not for CVD death. Conclusion Adolescent RHR is associated with future risk of HF and death, independently of BP, BMI and CRF, but not with CVD death, MI or IS, suggesting a causal pathway between elevated heart rate and myocardial dysfunction. [ABSTRACT FROM AUTHOR]

Background Recent research suggests that the prevalence of early heart failure may be on the rise. Compromised mental health in adolescence may help to explain this phenomenon. We aimed to investigate whether nonpsychotic mental disorder and low stress resilience in late adolescence were associated with increased risk of early heart failure. Methods A prospective cohort study of 18-year-old men (n = 1,784,450) who enlisted 1968–2005. At the conscription examination, 74,522 individuals were diagnosed with nonpsychotic mental disorders. Stress resilience was rated by psychologists; values were trichotomized. The risk of heart failure during the 46-year follow-up was calculated with Cox proportional hazards models. Baseline comorbidities, BMI, blood pressure, fitness, IQ, and parental education were included in the models. Results Incident cases of heart failure (n = 9962) were identified in the National Hospital Register. In fully adjusted models, increased risk of early heart failure was observed in males diagnosed with nonpsychotic mental disorders at conscription (hazard ratio (HR), 1.36; 95% confidence interval (CI), 1.25–1.47). The highest risk was seen among men with the risk factor alcohol/substance use (HR 1.90; 95% CI 1.59–2.28). Conscripts with the risk factor low stress resilience showed increased risk of heart failure compared to those with high scores (HR 1.41; 95% CI 1.30–1.53). Conclusion Nonpsychotic mental disorder, as well as low stress resilience in late adolescence may be associated with increased risk of early heart failure. Adolescence is potentially an important time for mental health interventions that may reduce both short and long-term consequences. [ABSTRACT FROM AUTHOR]

Background: Modifiable lifestyle factors in relation to risk for cardiomyopathy, a common and increasing cause of heart failure in the young, have not been widely studied. We sought to investigate a potential link between obesity, a recognized predictor of early heart failure, in adolescence and being diagnosed with cardiomyopathy in adulthood.Methods: This was a nationwide register-based prospective cohort study of 1 668 893 adolescent men (mean age, 18.3 years; SD, 0.7 years) who enlisted for compulsory military service from 1969 to 2005. At baseline, body mass index (BMI), blood pressure, and medical disorders were registered, along with test results for fitness and muscle strength. Cardiomyopathy diagnoses were identified from the National Hospital Register and Cause of Death Register during an up to 46-year follow-up and divided into categories: dilated, hypertrophic, alcohol/drug-induced, and other. Hazard ratios were calculated with Cox proportional hazards models.Results: During follow-up (median, 27 years; Q1-Q3, 19-35 years), 4477 cases of cardiomyopathy were identified, of which 2631 (59%) were dilated, 673 (15%) were hypertrophic, and 480 (11%) were alcohol/drug-induced. Increasing BMI was strongly associated with elevated risk of cardiomyopathy, especially dilated, starting at levels considered normal (BMI, 22.5-<25 kg/m2; hazard ratio, 1.38 [95% CI, 1.22-1.57]), adjusted for age, year, center, and baseline comorbidities, and with a >8-fold increased risk at BMI ≥35 kg/m2 compared with BMI of 18.5 to <20 kg/m2. For each 1-unit increase in BMI, similarly adjusted hazard ratios were 1.15 (95% CI, 1.14-1.17) for dilated cardiomyopathy, 1.09 (95% CI, 1.06-1.12) for hypertrophic cardiomyopathy, and 1.10 (1.06-1.13) for alcohol/drug-induced cardiomyopathy.Conclusions: Even mildly elevated body weight in late adolescence may contribute to being diagnosed with cardiomyopathy in adulthood. The already marked importance of weight control in youth is further strengthened by these findings, as well as greater evidence for obesity as a potential important cause of adverse cardiac remodeling that is independent of clinically evident ischemic heart disease. [ABSTRACT FROM AUTHOR]

Recent research suggests that the incidence of amyotrophic lateral sclerosis (ALS) may be on the rise. Since ALS becomes predominant in later life, most studies on causal factors are conducted in middle-aged or older populations where potentially important influences from early life can usually not be adequately captured. We aimed to investigate predictors in young Swedish men for ALS in adulthood. Therefore, we performed a prospective cohort study of young men (aged 16-25, n = 1,819,817) who enlisted 1968-2005 and took part in comprehensive conscription examinations. Incident cases of ALS (n = 526) during up to 46 years of follow-up were identified in the National Hospital Register and Swedish Cause of Death Register. Those who developed ALS had lower BMI (body mass index) at conscription than their peers (p = 0.03). The risk of ALS during follow-up was calculated with Cox proportional hazards models. No associations were found with physical fitness, erythrocyte sedimentation rate, or non-psychotic mental disorders. Low overall muscle strength compared to high overall muscle strength [hazard ratio (HR) 1.36; 95% confidence interval (CI) 1.01-1.83] and low BMI (a one-unit increase HR 0.96; 95% CI 0.93-0.99) and lower erythrocyte volume fraction (a one-unit increase HR 0.96; 95% CI 0.92-0.998) were the statistically significant predictors for ALS in adjusted models. These findings provide novel epidemiologic evidence of a prospective association between low overall muscle strength and erythrocyte volume fraction in young men and ALS risk. [ABSTRACT FROM AUTHOR]

The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids. We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir (n = 25), betamethasone (n = 41), both (n = 15), or neither (n = 42). Time to viral RNA clearance was analysed using Kaplan-Meier plots, categorical data were analysed using Fisher's exact test, and Kruskal-Wallis for continuous data. Viral RNA decline rate was analysed using a mixed effect model. We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance. Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response. [ABSTRACT FROM AUTHOR]

Background: Exposure to many contacts is the main risk factor for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, while risk of serious disease and death is chiefly determined by old age and comorbidities. Relative and population‐attributable fractions (PAFs) of multiple medical and social exposures for COVID‐19 outcomes have not been evaluated among older adults. Objectives: We describe the effect of multiple exposures on the odds of testing positive for the virus and of severe disease (hospital care or death) and PAFs in Swedish citizens aged 55 years and above. Methods: We used national registers to follow all citizens aged 55 years and above with respect to (1) testing positive, (2) hospitalization, and (3) death between 31 January 2020 and 1 February 2021. Results: Of 3,410,241 persons, 156,017 (4.6%, mean age 68.3 years) tested positive for SARS‐CoV‐2, while 35,999 (1.1%, mean age 76.7 years) were hospitalized or died (12,384 deaths, 0.4%, mean age 84.0 years). Among the total cohort, the proportion living without home care or long‐term care was 98.8% among persons aged 55–64 and 22.1% of those aged 95 and above. After multiple adjustment, home care and long‐term care were associated with odds ratios of 7.9 (95% confidence interval [CI] 6.8–9.1) and 22.5 (95% CI 19.6–25.7) for mortality, with PAFs of 21.9% (95% CI 20.9–22.9) and 33.3% (95% CI 32.4–34.3), respectively. Conclusion: Among Swedish residents aged 55 years and above, those with home care or long‐term care had markedly increased risk for COVID‐19 death during the first year of the pandemic, with over 50% of deaths attributable to these factors. [ABSTRACT FROM AUTHOR]

Background Congenital heart disease (CHD) is a lifelong predisposing condition for infective endocarditis (IE). As a consequence of advances in pediatric care, the number of adults with CHD is now exceeding the number of children. The goal of the present study was to determine the cumulative incidence of IE in patients with CHD and detect temporal changes compared with controls. Methods Nationwide registry-based case-control study of patients with CHD born 1930–2017 matched with 10 random controls. Infective endocarditis episodes were linked using the Swedish 10-digit personal identification number. Results In total, 89 541 patients with CHD and 890 470 matched controls were included. In patients with CHD, 1477 IE episodes were registered and 447 episodes in controls. Patients with CHD had 8.5% cumulative incidence of IE at age 87 years, compared with 0.7% in matched controls. Incidence rate of IE per 100 000 person-years was 65.5 (95% confidence interval [CI] 62.2–68.9) and 1.8 (95% CI: 1.7–2.0) in CHD patients and controls, respectively. By age 18 years, patients with CHD had an IE incidence similar to that of 81-year-old controls. Incidence of IE differed by age but not by birth year. Bacterial etiology was registered from 1997 in half of the IE episodes; among CHD IE cases, 43.3% were caused by streptococci and 29.8% by Staphylococcus aureus. Conclusions Infective endocarditis remains an important complication in patients with CHD. Incidence correlate with age and the number of IE episodes are expected to increase as the CHD population grow older. [ABSTRACT FROM AUTHOR]

Aims: Heart failure (HF) incidence appears to increase among younger individuals, raising questions of how risk factors affect the younger population. We investigated the association of cognitive performance in late adolescence with long-term risk of early HF.Methods and Results: We followed a cohort of Swedish men enrolled in mandatory military conscription in 1968-2005 (n = 1 225 300; mean age 18.3 years) until 2014 for HF hospitalization, using data from the Swedish National Inpatient Registry. Cognitive performance (IQ) was measured through a combination of tests, separately evaluating logical, verbal, visuospatial, and technical abilities. The results were standardized, weighted, and presented as stanines of IQ. The association between IQ and risk of HF was estimated using Cox proportional hazards models. In follow-up, there were 7633 cases of a first HF hospitalization (mean age at diagnosis 50.1 years). We found an inverse relationship between global IQ and risk of HF hospitalization. Using the highest IQ stanine as reference, the adjusted hazard ratio for the lowest IQ with risk of HF was 3.11 (95% confidence interval 2.60-3.71), corresponding to a hazard ratio of 1.32 (95% CI 1.28-1.35) per standard deviation decrease of IQ. This association proved persistent across predefined categories of HF with respect to pre-existing or concomitant co-morbidities; it was less apparent among obese conscripts (P for interaction =0.0004).Conclusion: In this study of young men, IQ was strongly associated with increased risk of early HF. The medical profession needs to be aware of this finding so as to not defer diagnosis. [ABSTRACT FROM AUTHOR]