Identifying people living with cystic fibrosis in the Danish National Patient Registry: A validation study.

BACKGROUND: The Danish National Patient Registry (DNPR) serves as a valuable resource for scientific research. However, to ensure accurate results in cystic fibrosis (CF) studies that rely on DNPR data, a robust case-identification algorithm is essential. This study aimed to develop and validate algorithms for the reliable identification of CF patients in the DNPR. METHODS: Using the Danish Cystic Fibrosis Registry (DCFR) as a reference, accuracy measures including sensitivity and positive predictive value (PPV) for case-finding algorithms deployed in the DNPR were calculated. Algorithms were based on minimum number of hospital contacts with CF as the main diagnosis and minimum number of days between first and last contact. RESULTS: An algorithm requiring a minimum of one hospital contact with CF as the main diagnosis yielded a sensitivity of 96.1 % (95 % CI: 94.2 %; 97.4 %) and a PPV of 84.9 % (82.0 %; 87.4 %). The highest-performing algorithm required minimum 2 hospital visits and a minimum of 182 days between the first and the last contact and yielded a sensitivity of 95.9 % (95 % CI: 94.1 %; 97.2 %), PPV of 91.0 % (95 % CI: 88.6 %; 93.0 %) and a cohort entry delay of 3.2 months at the 75th percentile (95th percentile: 38.7 months). CONCLUSIONS: The DNPR captures individuals with CF with high sensitivity and is a valuable resource for CF-research. PPV was improved at a minimal cost of sensitivity by increasing requirements of minimum number of hospital contacts and days between first and last contact. Cohort entry delay increased with number of required hospital contacts.

Association Between First-time Neurologic Events and Metronidazole Treatment: A Case-time Control Study.

PURPOSE: Metronidazole, a widely used antimicrobial medication, has been linked to neurologic adverse drug reactions. This study investigates the association between metronidazole use and first-time neurologic events. METHODS: We conducted a case-time-control study using data from the Danish National Patient Register and the National Prescription Register in years 2013 to 2021. Patients with a first-time diagnosis of encephalopathy, cerebellar dysfunction, or peripheral neuropathy were included. Conditional logistic regression analyses were performed to estimate the risk of neurologic events associated with metronidazole use. FINDINGS: Out of 476,066 first-time metronidazole prescriptions, the 100-day cumulative incidence of peripheral neuropathy was 0.016%, and 0.002% for cerebellar dysfunction or encephalopathy. In the case-time control study, we identified 17,667 persons with a first-time neurologic event and were included for the analysis. The estimated odds ratio for the combined neurologic events was 0.98 (95% CI, 0.59-1.64, P = 0.95) with no statistically significant association across different subgroups and time windows. IMPLICATIONS: Our findings suggest that metronidazole-induced neurologic events may be rarer than previously described, and we did not find any consistent or statistically significant association between metronidazole exposure. Nonetheless, clinicians should remain vigilant to potential neurologic risks in patients receiving metronidazole, to ensure its safe and effective use.

Education, employment, and income among people living with cystic fibrosis across three decades - A matched cohort study using Danish health registries.

BACKGROUND: Past and ongoing advancements in cystic fibrosis (CF) care warrant long-term analysis of the societal impact of the condition. This study aims to evaluate changes in key socioeconomic factors across three decades among people living with CF (pwCF), compared with both the general population and an early-onset chronic disease population. METHODS: This nationwide, registry-based, matched cohort study included all pwCF ≥ 18 years in Denmark in the years 1990, 2000, 2010, and 2018. Each person living with CF was matched to five individuals in the general population and five individuals living with type 1 diabetes or juvenile arthritis based on age, sex, and municipality. RESULTS: The Danish adult CF population increased nearly fourfold from 88 in 1990 to 331 in 2018, and mean age increased by ten years. The educational level of pwCF was similar to the two comparator cohorts, while pwCF were less often in employment and more often permanently outside the labor force. Personal and household income levels of the CF cohort were higher than those of the comparator cohorts. CONCLUSIONS: The disadvantage in employment for pwCF remained, but, over time, the societal profiles of the one-year CF cohorts increasingly converged with those of the comparator cohorts, indicative of improved clinical management, extended life expectancy, and the supportive role of the Danish welfare system in reducing health inequalities. Further research should be done to evaluate the effects of the newly introduced modulator therapies on employment, considering the broader societal impact and impact on quality of life.

Whole-cycle analysis of echocardiographic tissue Doppler velocities as a marker of biological age.

Purpose: Tissue Doppler imaging (TDI) is a sensitive marker of impaired cardiac function and different phases of the TDI curve carry different prognostic information. It is not known how continuous TDI curves change with age in normal subjects, and whether these changes differ from changes seen in individuals at risk of future cardiac events. Methods: A total of 1,763 individuals from the general population were examined with color TDI at the septal and lateral mitral sites. A low-risk group was defined as without cardiac risk factors (hypertension, diabetes or ischemic heart disease) at baseline and without any cardiac events (cardiovascular death or admission due to either heart failure or acute myocardial infarction) during 10-years follow-up. All TDI curves were corrected for heart rate, and whole-cycle analysis of age-related changes to TDI velocities was performed in both low-risk (n = 881) and high-risk individuals (n = 882). Results: In the low-risk population, four phases where myocardial velocity differed most (p < 10-10) according to age were identified [in a standardized cardiac cycle of 1 second (s)]: Systolic peak (0.09-0.13 s), systolic plateau (0.18-0.27 s), early diastole (0.43-0.54 s) and late diastole (0.88-0.95 s). With increasing age, systolic velocities decreased, early diastolic velocities decreased and had delayed peak, and late diastolic velocities increased until age 70 and then stopped increasing. In the high-risk population, comparison to corresponding age groups of the low-risk population showed: Lower early diastolic velocities in 20-40-year-olds; higher late diastolic velocities and lower peak systolic velocities in 40-60-year-olds; further decreased systolic velocities including the systolic plateau and decreased late diastolic velocities in 60-year-olds. The time segments around the systolic peak (p = 0.002) and early diastole (p < 0.001) differed significantly between the high-risk and low-risk population, thus making it possible to use the individual age gap between a TDI-derived biological age and the real chronological age as a tool to discriminate high-risk individuals from low-risk individuals. Conclusion: We found that individuals with cardiac risk factors display findings compatible with an accelerated aging of the heart and thus propose TDI-derived biological age as a tool to identify high-risk patients.

Left ventricular filling pressure by septal and lateral E/e' equally predict cardiovascular events in the general population.

PURPOSE: There exists no consensus on the site of E/e' measurement. This study aimed to evaluate the predictive value of septal and lateral E/e' along with the importance of their intra-individual difference. METHODS: In 1775 persons from the general population, peak early diastolic velocity (e') was obtained by color tissue Doppler at the septal and lateral mitral annular sites. The endpoint was combined of cardiovascular death or admission due to heart failure or acute myocardial infarction. RESULTS: During a median follow-up of 10.9 years, the endpoint occurred in 227 participants. E/e'septal and E/e'lateral were equally strong predictors of cardiac events; in age- and sex-adjusted models they did not differ in AUC (septal: 0.8385, lateral: 0.8389; p = 0.94) or in continuous NRI (p = 0.84). Models using E/e'average did not improve AUC or NRI, and the intra-individual difference between sites had no predictive value (p = 0.79). E/e'septal was generally higher than E/e'lateral, thus age- and sex-specific normal values were reported for both sites for a population free of cardiac events during 10 years of follow-up. CONCLUSIONS: Septal and lateral E/e' are equally useful in predicting cardiac events in the general population. Measuring both sites provides no further predictive value than measuring a single site.