Implications of Age for the Diagnostic and Prognostic Value of Cardiac Troponin T and I.

BACKGROUND: The influence of age on cardiac troponin is unclear and may vary between cardiac troponin T (cTnT) and I (cTnI). We aimed to compare the impact of age on the diagnostic and prognostic utility of cTnT and cTnI. METHODS: This Danish nationwide, register-based cohort study included patients with at least one cardiac troponin (cTn) measurement from 2009 through June 2022, stratified into decades of age. We used peak cTn concentration during admission, dichotomized as positive/negative and normalized to the 99th percentile. Receiver operating characteristics for myocardial infarction (MI) and logistic regression were used to estimate the odds ratio (OR) for mortality at 1 year. RESULTS: We included 541 817 patients; median age 66 years (interquartile range [IQR] 51-77) and 256 545 (47%) female. A total of 40 359 (7.4%) had an MI, and 59 800 (14.1%) patients died within 1 year of admission. The predictive ability of both cTns for MI were highest for patients 30 to 50 years. This was most pronounced for cTnT, the specificity of which fell from 83% among patients 40 to 49 years to 4% for patients ≥90 years. The prognostic ability of both cTns for 1-year mortality declined with age. cTnT had stronger prognostic ability for all age-groups; OR for a positive cTnT 28.4 (95% CI, 20.1-41.0) compared with 9.4 (95% CI, 5.0-16.7) for cTnI among patients <30 years. CONCLUSIONS: The predictive and prognostic ability of cTnT and cTnI declined with age. cTnT had a low specificity for MI in elderly patients. However, cTnT was the strongest prognostic marker among all age groups.

Prevalence and prognostic relevance of electrocardiographic abnormalities among patients with ANCA-associated vasculitis.

OBJECTIVES: Current guidelines provide limited evidence for cardiovascular screening in ANCA-associated vasculitis (AAV). This study aimed to investigate the prevalence of electrocardiogram (ECG) abnormalities and associations between no, minor or major ECG abnormalities with cardiovascular mortality in AAV patients compared with matched controls. METHOD: Using a risk-set matched cohort design, patients diagnosed with granulomatosis with polyangiitis or microscopic polyangiitis with digital ECGs were identified from Danish registers from 2000-2021. Patients were matched 1:3 to controls without AAV on age, sex, and year of ECG measurement. Associated hazards of cardiovascular mortality according to ECG abnormalities were assessed in Cox regression models adjusted for age, sex, and comorbidities, with subsequent computation of 5-year risk of cardiovascular mortality standardized to the age- and sex-distribution of the sample. RESULTS: A total of 1431 AAV patients were included (median age: 69 years, 52.3% male). Median follow-up was 4.8 years. AAV was associated with higher prevalence of left ventricular hypertrophy (17.5% vs 12.5%), ST-T deviations (10.1% vs 7.1%), atrial fibrillation (9.6% vs 7.5%), and QTc prolongation (5.9% vs 3.6%). Only AAV patients with major ECG abnormalities demonstrated significantly elevated risk of cardiovascular mortality [HR 1.99 (1.49-2.65)] compared with controls. This corresponded to a 5-year risk of cardiovascular mortality of 19.14% (16-22%) vs 9.41% (8-11%). CONCLUSION: Patients with AAV demonstrated a higher prevalence of major ECG abnormalities than controls. Notably, major ECG abnormalities were associated with a significantly increased risk of cardiovascular mortality. These results advocate for the inclusion of ECG assessment into routine clinical care for AAV patients.

The Danish Nationwide Electrocardiogram (ECG) Cohort.

The electrocardiogram (ECG) is a non-invasive diagnostic tool holding significant clinical importance in the diagnosis and risk stratification of cardiac disease. However, access to large-scale, population-based digital ECG data for research purposes remains limited and challenging. Consequently, we established the Danish Nationwide ECG Cohort to provide data from standard 12-lead digital ECGs in both pre- and in-hospital settings, which can be linked to comprehensive Danish nationwide administrative registers on health and social data with long-term follow-up. The Danish Nationwide ECG Cohort is an open real-world cohort including all patients with at least one digital pre- or in-hospital ECG in Denmark from January 01, 2000, to December 31, 2021. The cohort includes data on standardized and uniform ECG diagnostic statements and ECG measurements including global parameters as well as lead-specific measures of waveform amplitudes, durations, and intervals. Currently, the cohort comprises 2,485,987 unique patients with a median age at the first ECG of 57 years (25th-75th percentiles, 40-71 years; males, 48%), resulting in a total of 11,952,430 ECGs. In conclusion, the Danish Nationwide ECG Cohort represents a novel and extensive population-based digital ECG dataset for cardiovascular research, encompassing both pre- and in-hospital settings. The cohort contains ECG diagnostic statements and ECG measurements that can be linked to various nationwide health and social registers without loss to follow-up.

Poor socioeconomic outcomes: Completion of the final examination after lower secondary education mitigates risks associated with gestational age.

AIM: To investigate the influence of gestational age (GA) on the association between completion of the final examination after 10-11 years of basic education and education, financial independence and income in early adulthood. METHODS: A nationwide register-based study including individuals born in Denmark between 1990 and 1992. Completion of the examination was evaluated at age 18 and education, financial independence and income at age 28. RESULTS: Of 165 683 individuals included, 15.7%, 10.8% and 5.5% had low educational level, were not financially independent and had low income. For those who completed the examination odds ratio (OR) ranged from 1.03 at GA = 32-36 weeks to 1.25 at ≤27 weeks for low education, from 1.10 to 0.91 for not being financial independent and from 1.06 to 1.48 for low income. For those who did not complete the examination, OR increased from 7.55 at ≥37 weeks to 15.03 at ≤27 weeks for low education and from 4.68 to 15.31 for not being financial independent. For low income, OR was 2.57 and independent of GA. CONCLUSION: For individuals who completed the examination, the odds of poor socioeconomic outcomes were independent of GA. Individuals who did not complete the examination had increased odds of poor socioeconomic outcomes, particularly as GA decreased.

Five-year neurodevelopmental assessment of extremely preterm or extremely low birthweight infants: Association with school performance.

AIM: We investigated the associations between motor performance and IQ at 5 years of age and school difficulties and grade point averages (GPAs) at 18 years of age. Additionally, the accuracy of preschool IQ in predicting school difficulties was examined. METHODS: A nationwide follow-up study of children born in 1994-1995 who were <28 weeks of gestation or had a birthweight <1000 g. The Danish personal identification number was used to merge data from a national cohort study with population-based registries. Logistic regression analyses examined the associations between motor performance/IQ and school difficulties. Linear regression analyses and the area under the receiver operator curve (AUC) were used to examine the relationship between IQ and GPAs. RESULTS: The study population comprised 248 children, 37% were classified with school difficulties. Motor performance and IQ were associated with school difficulties. The odds of having school difficulties increased as IQ decreased, and the same pattern was observed for GPAs. IQ predicted school difficulties, with an AUC of 0.80 (confidence interval: 0.74-0.86). CONCLUSION: Preschool motor performance and IQ were associated with school difficulties. Additionally, IQ was linked to GPAs. As a screening tool, the predictive ability of preschool IQ for academic difficulties was moderate/high in this cohort.

All-cause mortality among Danish nursing home residents before and during the COVID-19 pandemic: a nationwide cohort study.

A substantial part of mortality during the COVID-19-pandemic occurred among nursing home residents which caused alarm in many countries. We investigate nursing home mortality in relation to the expected mortality prior to the pandemic. This nationwide register-based study included all 135,501 Danish nursing home residents between 2015 until October 6, 2021. All-cause mortality rates were calculated using a standardization method on sex and age distribution of 2020. Survival probability and lifetime lost for 180 days was calculated using Kaplan Meier estimates. Of 3,587 COVID-19 related deaths, 1137 (32%) occurred among nursing home residents. The yearly all-cause mortality rates per 100,000 person-years in 2015, 2016, and 2017 were 35,301 (95% CI: 34,671-35,943), 34,801 (95% CI: 34,180-35,432), and 35,708 (95% CI: 35,085-36,343), respectively. Slightly elevated mortality rates per 100,000 person-years were seen in 2018, 2019, 2020, and 2021 of 38,268 (95% CI: 37,620-38,929), 36,956 (95% CI: 36,323-37,600), 37,475 (95% CI: 36,838-38,122), and 38,536 (95% CI: 37,798-39,287), respectively. For SARS-CoV-2-infected nursing home residents, lifetime lost difference was 42 days (95% CI: 38-46) in 2020 versus non-infected in 2018. Among vaccinated in 2021, lifetime lost difference was 25 days (95% CI: 18-32) for SARS-CoV-2-infected versus non-infected. Even though a high proportion of COVID-19 fatalities took place in nursing homes and SARS-CoV-2-infection increased the risk of individual death, the annual mortality was only slightly elevated. For future epidemics or pandemics reporting numbers of fatal cases in relation to expected mortality is critical.

Consequences of COVID-19-related lockdowns and reopenings on emergency hospitalizations in pediatric patients in Denmark during 2020-2021.

There is a considerable burden of children being hospitalized due to infectious diseases worldwide. The COVID-19 pandemic provided a unique opportunity to examine effects of worldwide efforts to control spread of infection. We aimed to investigate overall age-specific hospitalizations due to viral and bacterial infections and diseases triggered by respiratory tract infections during and after lockdown. This nationwide register-based observational study included children from 29 days to 17 years old hospitalized in all Danish pediatric emergency departments during the years 2015-2021. Main outcomes were ICD-10 diagnoses for infectious diseases and infection triggered illnesses. Fluctuations in hospitalization events were explored using figures with weekly events per 100,000. Total events followed a predictable pattern during 2015-2019. In 2020-2021, there was a drop in hospital encounters after lockdowns and surge after reopenings. In 2021, there was a surge of hospital encounters in the late summer due to respiratory syncytial virus infections and asthmatic bronchitis mostly in infants from 29 days to 2 years. For the infectious diseases, there was a dramatic decrease in events after lockdowns and immediate increase in cases that followed the same pattern of previous years after reopenings. Bacterial infections, like urinary tract infections, sepsis, and meningitis followed a steady pattern throughout all calendar-years. CONCLUSIONS: Nationwide efforts to minimize infectious disease spread like lockdowns have a preventative and period lasting effect but reopenings/reunions result in surges of infectious diseases. This might be due to children not getting immunized steadily thereby increasing the pool of possible hosts for potential viral infections. WHAT IS KNOWN: • There is a seasonal fluctuation in viral/respiratory infections in children with higher infection rates in the winter and lower rates in the summer. • RSV infection is a major source of concern. WHAT IS NEW: • Major lockdowns and reopenings disrupt the seasonal fluctuations which can result in high surges in infections that increases the burden of children emergency departments and the risk of serious complications.

Household Exposure to Severe Acute Respiratory Syndrome Coronavirus 2 and Association With Coronavirus Disease 2019 Severity: A Danish Nationwide Cohort Study.

BACKGROUND: Households are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Severity of coronavirus disease 2019 (COVID-19) is likely associated with the infectious dose of SARS-CoV-2 exposure. We therefore aimed to assess the association between SARS-CoV-2 exposure within households and COVID-19 severity. METHODS: We performed a Danish, nationwide, register-based, cohort study including laboratory-confirmed SARS-CoV-2-infected individuals from 22 February 2020 to 6 October 2020. Household exposure to SARS-CoV-2 was defined as having 1 individual test positive for SARS-CoV-2 within the household. Cox proportional hazards models were used to estimate the association between "critical COVID-19" within and between households with and without secondary cases. RESULTS: From 15 063 multiperson households, 19 773 SARS-CoV-2-positive individuals were included; 11 632 were categorized as index cases without any secondary household cases; 3431 as index cases with secondary cases, that is, 22.8% of multiperson households; and 4710 as secondary cases. Critical COVID-19 occurred in 2.9% of index cases living with no secondary cases, 4.9% of index cases with secondary cases, and 1.3% of secondary cases. The adjusted hazard ratio for critical COVID-19 among index cases vs secondary cases within the same household was 2.50 (95% confidence interval [CI], 1.88-3.34), 2.27 (95% CI, 1.77-2.93) for index cases in households with no secondary cases vs secondary cases, and 1.1 (95% CI, .93-1.30) for index cases with secondary cases vs index cases without secondary cases. CONCLUSIONS: We found no increased hazard ratio of critical COVID-19 among household members of infected SARS-CoV-2 index cases.

All-cause mortality and location of death in patients with established cardiovascular disease before, during, and after the COVID-19 lockdown: a Danish Nationwide Cohort Study.

BACKGROUND: On 13 March 2020, the Danish authorities imposed extensive nationwide lockdown measures to prevent the spread of the coronavirus disease 2019 (COVID-19) and reallocated limited healthcare resources. We investigated mortality rates, overall and according to location, in patients with established cardiovascular disease before, during, and after these lockdown measures. METHODS AND RESULTS: Using Danish nationwide registries, we identified a dynamic cohort comprising all Danish citizens with cardiovascular disease (i.e. a history of ischaemic heart disease, ischaemic stroke, heart failure, atrial fibrillation, or peripheral artery disease) alive on 2 January 2019 and 2020. The cohort was followed from 2 January 2019/2020 until death or 16/15 October 2019/2020. The cohort comprised 340 392 and 347 136 patients with cardiovascular disease in 2019 and 2020, respectively. The overall, in-hospital, and out-of-hospital mortality rate in 2020 before lockdown was significantly lower compared with the same period in 2019 [adjusted incidence rate ratio (IRR) 0.91, 95% confidence interval (CI) CI 0.87-0.95; IRR 0.95, 95% CI 0.89-1.02; and IRR 0.87, 95% CI 0.83-0.93, respectively]. The overall mortality rate during and after lockdown was not significantly different compared with the same period in 2019 (IRR 0.99, 95% CI 0.97-1.02). However, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during and after lockdown compared with the same period in 2019 (in-hospital, IRR 0.92, 95% CI 0.88-0.96; out-of-hospital, IRR 1.04, 95% CI1.01-1.08). These trends were consistent irrespective of sex and age. CONCLUSIONS: Among patients with established cardiovascular disease, the in-hospital mortality rate was lower and out-of-hospital mortality rate higher during lockdown compared with the same period in the preceding year, irrespective of age and sex.

Association Between Male Sex and Outcomes of Coronavirus Disease 2019 (COVID-19)-A Danish Nationwide, Register-based Study.

BACKGROUND AND OBJECTIVES: Male sex has been associated with severe coronavirus disease 2019 (COVID-19) infection. We examined the association between male sex and severe COVID-19 infection and if an increased risk remains after adjustment for age and comorbidities. METHODS: Nationwide register-based follow-up study of COVID-19 patients in Denmark until 16 May 2020. Average risk ratio comparing 30-day composite outcome of all-cause death, severe COVID-19 diagnosis or intensive care unit (ICU) admission for men versus women standardized to the age and comorbidity distribution of all patients were derived from multivariable Cox regression. Included covariates were age, hypertension, diagnoses including obesity, alcohol, sleep apnea, diabetes, chronic obstructive pulmonary disease, previous myocardial infarction (MI), ischemic heart disease (IHD), heart failure (HF), atrial fibrillation (AF), stroke, peripheral artery disease, cancer, liver, rheumatic, and chronic kidney disease (CKD). RESULTS: Of 4842 COVID-19 patients, 2281 (47.1%) were men. Median age was 57 [25%-75% 43-73] for men versus 52 [38-71] for women (P < .001); however, octogenarians had equal sex distribution. Alcohol diagnosis, diabetes, hypertension, sleep apnea, prior MI and IHD (all P < .001) as well as AF, stroke, and HF (all P = .01) were more often seen in men, and so was CKD (P = .03). Obesity diagnosis (P < .001) were more often seen in women. Other comorbidity differences were insignificant (P > .05). The fully adjusted average risk ratio was 1.63 [95% CI, 1.44-1.84]. CONCLUSIONS: Men with COVID-19 infection have >50% higher risk of all-cause death, severe COVID-19 infection, or ICU admission than women. The excess risk was not explained by age and comorbidities.

Severe mental illness is associated with increased mortality and severe course of COVID-19.

OBJECTIVE: Psychiatric disorders have been associated with unfavourable outcome following respiratory infections. Whether this also applies to coronavirus disease 2019 (COVID-19) has been scarcely investigated. METHODS: Using the Danish administrative databases, we identified all patients with a positive real-time reverse transcription-polymerase chain reaction test for COVID-19 in Denmark up to and including 2 January 2021. Multivariable cox regression was used to calculate 30-day absolute risk and average risk ratio (ARR) for the composite end point of death from any cause and severe COVID-19 associated with psychiatric disorders, defined using both hospital diagnoses and redemption of psychotropic drugs. RESULTS: We included 144,321 patients with COVID-19. Compared with patients without psychiatric disorders, the standardized ARR of the composite outcome was significantly increased for patients with severe mental illness including schizophrenia spectrum disorders 2.43 (95% confidence interval [CI], 1.79-3.07), bipolar disorder 2.11 (95% CI, 1.25-2.97), unipolar depression 1.70 (95% CI, 1.38-2.02), and for patients who redeemed psychotropic drugs 1.70 (95% CI, 1.48-1.92). No association was found for patients with other psychiatric disorders 1.13 (95% CI, 0.86-1.38). Similar results were seen with the outcomes of death or severe COVID-19. Among the different psychiatric subgroups, patients with schizophrenia spectrum disorders had the highest 30-day absolute risk for the composite outcome 3.1% (95% CI, 2.3-3.9%), death 1.2% (95% CI, 0.4-2.0%) and severe COVID-19 2.7% (95% CI, 1.9-3.6%). CONCLUSION: Schizophrenia spectrum disorders, bipolar disorder, unipolar depression and psychotropic drug redemption are associated with unfavourable outcomes in patients with COVID-19.

Consequences of coronavirus disease-2019 (COVID-19) lockdown on infection-related hospitalizations among the pediatric population in Denmark.

It remains unknown how Coronavirus disease-2019 (COVID-19) prevention measures implemented on March 12, 2020, have affected the rate of pediatric infection-related hospitalizations in Denmark. Therefore, we investigated the rate of pediatric infection-related hospitalizations during the COVID-19 pandemic. We used a retrospective cohort design and included all Danish children < 18 years. Infection-related hospitalizations were assessed during study periods in 2020 vs. 2018/2019, and we computed incidence rate ratios (IRRs) with 95% confidence intervals (CIs) using Poisson regression. In the 2020 study period, 3093 children were hospitalized with an infection, while the corresponding figures for 2018 and 2019 study periods were 4824 and 3830, respectively. When comparing the 2020 to the 2018/2019 study period prior to nationwide lockdown, we observed a decline in infection-related hospitalizations (12.68 (95% CI, 12.22-13.16) vs. 15.49 (95% CI, 15.12-15.86) per 1000 person-years). We further observed decreased IRRs, especially during the lockdown period (week 11: 0.64 (95% CI, 0.55-0.75); week 12: 0.26 (95% CI, 0.21-0.33); week 13: 0.13 (95% CI, 0.10-0.19)).Conclusion: The rate of pediatric infection-related hospitalizations in Denmark declined during the COVID-19 pandemic in 2020 compared to that in 2018/2019, with a 36% decline during initiation of the nationwide lockdown period. What is Known: • Due to the COVID-19 pandemic, several countries have implemented mitigation strategies such as lockdown of non-critical business functions. Most of these strategies have previously been proven effective on interruption of infection transmission. • It remains unclear how the mitigation strategies have affected the rate of pediatric infection-related hospitalizations. What is New: • Insight on how COVID-19 prevention measures have affected the frequency of infection-related hospitalization. • Valuable knowledge on how to act in potential future pandemics.

National all-cause mortality during the COVID-19 pandemic: a Danish registry-based study.

Denmark implemented early widespread social distancing to reduce pressure on the healthcare system from the coronavirus disease 2019 (COVID-19) pandemic, with the aims to reduce mortality. Unintended consequences might be delays in treatment for other diseases and subsequent mortality. We examined national all-cause mortality comparing weeks 1-27 in 2020 and 2015-2019. This registry-based study used Danish national registry data until 5 July 2020. We examined all-cause mortality rates among all deaths recorded from 2015 to 2020 and among chronic conditions (cardiovascular (cardiac & circulatory), chronic pulmonary, chronic kidney disease, cancer, and diabetes), comparing each week in 2020 to weeks in 2015-2019. In 2020, there were 28,363 deaths in weeks 1-27 (30 December 2019-5 July 2020), the mean deaths in 2015-2019 were 28,630 deaths (standard deviation 784). Compared to previous years, the mortality rate in weeks 3-10 of 2020 was low, peaking in week 14 (17.6 per 100,000 persons in week 9, 19.9 per 100,000 in week 14). Comorbidity prevalence among deceased individuals was similar in 2020 and 2015-2019: 71.1% of all deceased had a prior cardiovascular diagnosis, 30.0% of all deceased had a prior cardiac diagnosis. There were 493 deaths with COVID-19 in weeks 11-27, (59.8% male), and 75.1% had a prior cardiovascular diagnosis. Weekly mortality rates for pre-existing chronic conditions peaked in week 14, and then declined. During the COVID-19 pandemic, due to timely lockdown measures, the mortality rate in Denmark has not increased compared to the mortality rates in the same period during 2015-2019.

In utero exposure to antiepileptic drugs is associated with learning disabilities among offspring.

OBJECTIVES: In utero exposure to antiepileptic drugs has previously been associated with adverse outcome among offspring, but evidence on longer term milestone development remains limited. We investigated the association between in utero exposure to antiepileptic drugs and learning disabilities in the first year of compulsory education among offspring and assessed which antiepileptic drugs carried the highest risk. METHODS: This population-based case-cohort study used Danish nationwide register data from 2005 to 2008. Cases were offspring exposed to antiepileptic drugs in utero, and controls were unexposed offspring of mothers previously redeeming antiepileptic drug prescriptions. Offspring were followed from birth until the first year of compulsory education from 2011 to 2015. Learning disabilities were defined as mental retardation, specific developmental disorders, autism spectrum disorders, emotional/behavioural disorders or having special educational needs. Logistic regression was used to compute ORs with 95% CIs adjusted for potential confounding. RESULTS: Of 117 475 incident singleton births, 636 cases and 434 controls were included (median age: 6.1 years, males: 55.7%). Learning disabilities were identified among 7.1% cases compared with 3.7% for controls. During any trimester, the adjusted OR of the association between in utero exposure to antiepileptic drugs and learning disabilities was 2.20 (95% CI 1.16 to 4.17). Among cases not exposed to polytherapy (n=556), in utero exposure to lamotrigine compared with another antiepileptic drug was associated with the lowest adjusted risk (OR 0.42, 95% CI 0.19 to 0.92), and valproate carried a higher risk (OR 4.67, 95% CI 1.73 to 12.59). CONCLUSION: In utero exposure to antiepileptic drugs was significantly associated with learning disabilities among offspring. Lamotrigine should preferentially be considered over, for example, valproate if clinically feasible.

The indirect and direct pathways between physical fitness and academic achievement on commencement in post-compulsory education in a historical cohort of Danish school youth.

BACKGROUND: Some studies have found positive associations between physical fitness and academic achievements. Pupils' academic achievements should indicate scholastic abilities to commence a post-compulsory education. However, the effect magnitude of physical fitness and academic achievements on commencement in post-compulsory education is unknown. We examined the pathways between physical fitness and academic achievement on pupils' commencement in post-compulsory education. METHODS: This historical cohort study followed 530 girls and 554 boys from the Danish municipality of Aalborg in the period 2008-2014, 13 to 15 years old in 2010. Physical fitness was assessed through a watt-max cycle ergometer test represented as VO2max (mL·kg-1·min-1). Academic achievement, commencement status and information on covariates were obtained from Danish nationwide registers. Causal inference based mediation analysis was used to investigate the indirect and direct pathways by separating the total effect of physical fitness on post-compulsory education commencement. RESULTS: Adjusting for sex, age, ethnicity and socioeconomic status, the overall mediation analysis showed an odds ratio (OR) of 1.87 (95% confidence interval (CI): 1.30; 2.73) for the total effect, corresponding to an increase in odds of post-compulsory education commencement when the physical fitness was increased by 10 units of VO2max. The separated total effect showed a natural direct OR of 1.36 (95% CI: 0.93; 1.98) and a natural indirect (i.e., through academic achievement) OR of 1.37 (95% CI: 1.20; 1.57). Thus, 51% (95% CI: 27%; 122%) of the effect of physical fitness on post-compulsory education commencement was mediated through academic achievement. CONCLUSION: Physical fitness had a positive effect on post-compulsory education commencement. A substantial part of this effect was mediated through academic achievement.

Fluoroquinolones do not provide added risk of out-of-hospital cardiac arrest: a nationwide study.

AIM: Conflicting results have been reported regarding the association between fluoroquinolones (FQs) and the risk of out-of-hospital cardiac arrest (OHCA). In particular, it has not become clear whether OHCA in FQ users is related to the inherent comorbidities or whether there is a direct pro-arrhythmic effect of FQs. Therefore, we studied the relation between FQs and OHCA in the general population. METHODS: Through Danish nationwide registries, we conducted a nested case-control study with OHCA cases of presumed cardiac causes and age/sex/OHCA date-matched non-OHCA controls from the general population. Conditional logistic regression models with adjustments for well-known risk factors of OHCA were employed to estimate the OR with 95% CI of OHCA comparing FQs with amoxicillin. RESULTS: The study population consisted of 46 578 OHCA cases (mean: 71 years (SD: 14.40), 68.8% men) and 232 890 matched controls. FQ was used by 276 cases and 328 controls and conferred no increase in the odds of OHCA compared with amoxicillin use after controlling for the relevant confounders (OR: 0.91 (95% CI: 0.71 to 1.16)). The OR of OHCA associated with FQ use did not vary significantly by age (OR≤65: 0.96 (95% CI: 0.53 to 1.74), OR>65: 0.88 (95% CI: 0.67 to 1.16), p value interaction=0.7818), sex (ORmen: 0.96 (95% CI: 0.70 to 1.31), ORwomen: 0.80 (95% CI: 0.53 to 1.20), p value interaction=0.9698) and pre-existing cardiovascular disease (ORabsent: 1.02 (95% CI: 0.57 to 1.82), ORpresent: 0.98 (95% CI: 0.75 to 1.28), p value interaction=0.3884), including heart failure (ORabsent: 0.93 (95% CI: 0.72 to 1.22), ORpresent: 1.11 (95% CI: 0.61 to 2.02), p value interaction=0.7083) and ischaemic heart disease (ORabsent: 0.85 (95% CI: 0.64 to 1.12), ORpresent: 1.38 (95% CI: 0.86 to 2.21), p value interaction=0.6230). CONCLUSION: Our findings do not support an association between FQ exposure and OHCA in the general population. This lack of association was consistent in men and women, in all age categories, and in the presence or absence of cardiovascular disease.

Overweight in childhood and consumer purchases in a Danish cohort.

BACKGROUND: Prevention and management of childhood overweight involves the entire family. We aimed to investigate purchase patterns in households with at least one member with overweight in childhood by describing expenditure on different food groups. METHODS: This Danish register-based cohort study included households where at least one member donated receipts concerning consumers purchases in 2019-2021 and at least one member had their Body mass index (BMI) measured in childhood within ten years prior to first purchase. A probability index model was used to evaluate differences in proportion expenditure spent on specific food groups. RESULTS: We identified 737 households that included a member who had a BMI measurement in childhood, 220 with overweight and 517 with underweight or normal weight (reference households). Adjusting for education, income, family type, and urbanization, households with a member who had a BMI classified as overweight in childhood had statistically significant higher probability of spending a larger proportion of expenditure on ready meals 56.29% (95% CI: 51.70;60.78) and sugary drinks 55.98% (95% CI: 51.63;60.23). Conversely, they had a statistically significant lower probability of spending a larger proportion expenditure on vegetables 38.44% (95% CI: 34.09;42.99), compared to the reference households. CONCLUSION: Households with a member with BMI classified as overweight in childhood spent more on unhealthy foods and less on vegetables, compared to the reference households. This study highlights the need for household/family-oriented nutrition education and intervention.

Oxidative Stress-Induced Damage to RNA and DNA and Mortality in Individuals with Psychiatric Illness.

Importance: All-cause mortality and the risk for age-related medical disease is increased in individuals with psychiatric illness, but the underlying biological mechanisms are not known. Oxidative stress on nucleic acids (DNA and RNA; NA-OXS) is a molecular driver of aging and a potential pathophysiological mechanism in a range of age-related disorders. Objective: To study the levels of markers of NA-OXS in a large cohort of community-dwelling individuals with and without psychiatric illness and to evaluate their association with prospective all-cause mortality. Design, Setting, and Participants: This cohort study used a combined cohort of participants from 2 population-based health studies: the Danish General Suburban Population Study (January 2010 to October 2013) and nondiabetic control participants from the Vejle Diabetes Biobank study (March 2007 to May 2010). Individual history of psychiatric illness was characterized using register data on psychiatric diagnoses and use of psychotropic drugs before baseline examination. Urinary markers of systemic RNA (8-oxo-7,8-dihydroguanosine [8-oxoGuo]) and DNA (8-oxo-7,8-dihydro-2'-deoxyguanosine [8-oxodG]) damage from oxidation were measured by ultraperformance liquid chromatography-tandem mass spectrometry. Cox proportional hazard regression models were applied for survival analyses, using register-based all-cause mortality updated to May 2023. The follow-up time was up to 16.0 years. Exposures: History of psychiatric illness. Main Outcomes and Measures: Mortality risk according to psychiatric illness status and 8-oxoGuo or 8-oxodG excretion level. Results: A total of 7728 individuals were included (3983 [51.5%] female; mean [SD] age, 58.6 [11.9] years), 3095 of whom (40.0%) had a history of psychiatric illness. Mean (SD) baseline 8-oxoGuo was statistically significantly higher in individuals with psychiatric illness than in those without (2.4 [1.2] nmol/mmol vs 2.2 [0.9] nmol/mmol; P < .001), whereas 8-oxodG was not. All-cause mortality was higher in the psychiatric illness group vs the no psychiatric illness group (hazard ratio [HR], 1.44; 95% CI, 1.27-1.64; P < .001) and increased sequentially with each increasing tertile of 8-oxoGuo excretion in both groups to an almost doubled risk in the psychiatric illness/high 8-oxoGuo group compared to the no psychiatric illness/low 8-oxoGuo reference group (HR, 1.99; 95% CI, 1.58-2.52; P < .001). These results persisted after adjustment for a range of potential confounders and in a sensitivity analysis stratified for sex. Conclusions and Relevance: This study establishes systemic oxidative stress-induced damage to RNA as a potential mechanism in the accelerated aging observed in psychiatric disorders and urinary 8-oxoGuo as a potentially useful marker of mortality risk in individuals with psychiatric illness.