Josefina Robertson

OBJECTIVES: To examine survival and long term cessation of injecting in a cohort of drug users and to assess the influence of opiate substitution treatment on these outcomes. DESIGN: Prospective open cohort study. SETTING: A single primary care facility in Edinburgh. PARTICIPANTS: 794 patients with a history of injecting drug use presenting between 1980 and 2007; 655 (82%) were followed up by interview or linkage to primary care records and mortality register, or both, and contributed 10,390 person years at risk; 557 (85%) had received opiate substitution treatment. MAIN OUTCOME MEASURES: Duration of injecting: years from first injection to long term cessation, defined as last injection before period of five years of non-injecting; mortality before cessation; overall survival. RESULTS: In the entire cohort 277 participants achieved long term cessation of injecting, and 228 died. Half of the survivors had poor health related quality of life. Median duration from first injection to death was 24 years for participants with HIV and 41 years for those without HIV. For each additional year of opiate substitution treatment the hazard of death before long term cessation fell 13% (95% confidence interval 17% to 9%) after adjustment for HIV, sex, calendar period, age at first injection, and history of prison and overdose. Conversely exposure to opiate substitution treatment was inversely related to the chances of achieving long term cessation. CONCLUSIONS: Opiate substitution treatment in injecting drug users in primary care reduces this risk of mortality, with survival benefits increasing with cumulative exposure to treatment. Treatment does not reduce the overall duration of injecting.

AIMS: To study the relation between body mass index (BMI) in young men and risk of early hospitalization with heart failure. METHODS AND RESULTS: In a prospective cohort study, men from the Swedish Conscript Registry investigated 1968-2005 (n = 1 610 437; mean age, 18.6 years were followed 5-42 years (median, 23.0 years; interquartile range, 15.0-32.0), 5492 first hospitalizations for heart failure occurred (mean age at diagnosis, 46.6 (SD 8.0) years). Compared with men with a body mass index (BMI) of 18.5-20.0 kg/m2, men with a BMI 20.0-22.5 kg/m2 had an hazard ratio (HR) of 1.22 (95% CI, 1.10-1.35), after adjustment for age, year of conscription, comorbidities at baseline, parental education, blood pressure, IQ, muscle strength, and fitness. The risk rose incrementally with increasing BMI such that men with a BMI of 30-35 kg/m2 had an adjusted HR of 6.47 (95% CI, 5.39-7.77) and those with a BMI of ≥35 kg/m2 had an HR of 9.21 (95% CI, 6.57-12.92). The multiple-adjusted risk of heart failure per 1 unit increase in BMI ranged from 1.06 (95% CI, 1.02-1.11) in heart failure associated with valvular disease to 1.20 (95% CI, 1.18-1.22) for cases associated with coronary heart disease, diabetes, or hypertension. CONCLUSION: We found a steeply rising risk of early heart failure detectable already at a normal body weight, increasing nearly 10-fold in the highest weight category. Given the current obesity epidemic, heart failure in the young may increase substantially in the future and physicians need to be aware of this.

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/m 2 ; 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/m 2 compared with BMI of 18.5 to <20 kg/m 2 . 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.

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.

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/m 2 , 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/m 2 ), 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.