Long-Term Mortality in Patients Diagnosed with Meningococcal Disease: A Danish Nationwide Cohort Study

Background: In contrast to the case fatality rate of patients diagnosed with meningococcal disease (MD) the long-term mortality in these patients is poorly documented. Methodology/Principal Findings: We performed a nationwide, population-based cohort study including all Danish patients diagnosed with MD from 1977 through 2006 and alive one year after diagnosis. Data was retrieved from the Danish National Hospital Register, the Danish Civil Registration System and the Danish Register of Causes of Death. For each patient four age- and gender-matched individuals were identified from the population cohort. The siblings of the MD patients and of the individuals from the population cohort were identified. We constructed Kaplan-Meier survival curves and used Cox regression analysis, cumulative incidence function and subdistribution hazard regression to estimate mortality rate ratios (MRR) and analyze causes of death. We identified 4,909 MD patients, 19,636 individuals from the population cohort, 8,126 siblings of MD patients and 31,140 siblings of the individuals from the population cohort. The overall MRR for MD patients was 1.27 (95 % confidence interval (CI), 1.12–1.45), adjusted MRR, 1.21 (95 % CI, 1.06–1.37). MD was associated with increased risk of death due to nervous system diseases (MRR 3.57 (95 % CI, 1.82–7.00). No increased mortality due to infections, neoplasms or cardiovascular diseases was observed. The MRR for siblings of MD patients compared with siblings of the individuals from the population cohort was 1.17 (95 % CI, 0.92–1.48)

Hepatitis C prevalence in Denmark in 2016—An updated estimate using multiple national registers

Background: Chronic hepatitis C (CHC) can be eliminated as a public health threat by meeting the WHO targets: 90% of patients diagnosed and 80% treated by 2030. To achieve and monitor progress towards elimination, an updated estimate of the size of the CHC population is needed, but Denmark has no complete national CHC register. By combining existing registers in 2007, we estimated the population living with CHC to be 16,888 (0.38% of the adult population). Aim: To estimate the population living with diagnosed and undiagnosed CHC in Denmark on 31 December 2016. Among additional aims were to estimate the proportion of patients attending specialised clinical care. Methods: People with diagnosed CHC were identified from four national registers. The total diagnosed population was estimated by capture-recapture analysis. The undiagnosed population was estimated by comparing the register data with data from two cross-sectional surveys. Results: The population living with diagnosed CHC in Denmark was 7,581 persons (95%CI: 7,416–12,661) of which 6,116 (81%) were identified in the four registers. The estimated undiagnosed fraction was 24%, so the total CHC infected population was 9,975 corresponding to 0.21% of the adult population (95%CI: 9,758–16,659; 0.21%-0.36%). Only 48% of diagnosed patients had received specialised clinical care. Conclusion: CHC prevalence in Denmark is declining and 76% of patients have been diagnosed. Linking diagnosed patients to care and increasing efforts to test people with former or current drug use will be necessary to achieve CHC elimination

Osteoprotegerin and cardiovascular mortality in patients with non-ST elevation acute coronary syndromes

Objective: To assess the relationship between osteoprotegerin (OPG) and cardiovascular death, and the pathobiological mechanisms contributing to the association, in acute coronary syndromes (ACS). Design: Prospective observational. Setting: Biomarker substudy of MERLIN-TIMI 36, a randomised, placebo controlled trial of ranolazine in non-ST elevation (NSTE)-ACS. Patients: 4463 patients with NSTE-ACS. Interventions: Ranolazine or placebo. Main outcome measures: Incidence of cardiovascular death (CV death); additionally, heart failure (HF), cardiac arrhythmias, inhospital ischaemia, severe recurrent ischaemia or recurrent myocardial infarction (MI). Results: During a median follow-up of 341 days, 208 patients died of cardiovascular causes. The OPG baseline concentration was strongly associated with both 30 day and 1 year incidence of CV death. After adjustment for conventional risk markers, OPG concentrations (log transformed) remained a significant predictor of CV death by 30 days (HR (95% CI) 2.32 (1.30 to 4.17); p¼0.005) and by 1 year (HR 1.85 (1.33 to 2.59); p<0.001). Baseline levels of OPG were also an independent predictor of new or worsening HF at 30 days (HR 2.25 (1.38 to 3.69); p¼0.001) and 1 year (HR 1.81 (1.26 to 2.58) p¼0.001). By univariable analysis, higher OPG was associated with both early ischaemic and arrhythmic events. Although OPG levels were associated with recurrent MI within 12 months, this association was attenuated and no longer significant after multivariable adjustment. Conclusions: OPG is independently associated with 30 day and 1 year risk of cardiovascular mortality and HF development after NSTE-ACS. As no independent relationship between OPG levels and recurrent ischaemia or MI was observed, myocardial dysfunction may be a more important stimulus for OPG production than ischaemia in ACS

Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): a 2 x 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol

Aims: Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the {beta}-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. Methods and results: In a 2 x 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the {beta}-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI −0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. Conclusion: In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function

Cardiac troponin measurement at the point of care: educational recommendations on analytical and clinical aspects by the IFCC Committee on Clinical Applications of Cardiac Bio-Markers (IFCC C-CB).

The International Federation of Clinical Chemistry and Laboarator Medicine (IFCC) Committee on Clinical Applications of Cardiac Bio-Markers (C-CB) has provided evidence-based educational resources to aid and improve the understanding of important analytical and clinical aspects of cardiac biomarkers. The present IFCC C-CB educational report focuses on recommendations for appropriate use, analytical performance, and gaps in clinical studies related to the use of cardiac troponin (cTn) by point of care (POC) measurement, often referred to as a point of care testing (POCT). The use of high-sensitivity (hs)-cTn POC devices in accelerated diagnostic protocols used in emergency departments or outpatient clinics investigating acute coronary syndrome has the potential for improved efficacy, reduction of length of stay and reduced costs in the health care system. POCT workflow integration includes location of the instrument, assignment of collection and testing responsibility to (non-lab) staff, instrument maintenance, in-service and recurrent training, quality control, proficiency assessments, discrepant result trapping, and troubleshooting and inventory management

Cardiac Troponin Assays With Improved Analytical Quality: A Trade-Off Between Enhanced Diagnostic Performance and Reduced Long-Term Prognostic Value.

Background Cardiac troponin (cTn) permits early rule-out/rule-in of patients admitted with possible non-ST-segment-elevation myocardial infarction. In this study, we developed an admission and a 0/1 hour rule-out/rule-in algorithm for a troponin assay with measurable results in >99% of healthy individuals. We then compared its diagnostic and long-term prognostic properties with other protocols. Methods and Results Blood samples were collected at 0, 1, 3, and 8 to 12 hours from patients admitted with possible non-ST-segment-elevation myocardial infarction. cTnT (Roche Diagnostics), cTnI(Abbott) (Abbott Diagnostics), and cTnI(sgx) (Singulex Clarity System) were measured in 971 admission and 465 1-hour samples. An admission and a 0/1 hour rule-out/rule-in algorithm were developed for the cTnI(sgx) assay and its diagnostic properties were compared with cTnTESC (European Society of Cardiology), cTnI(Abbott)ESC, and 2 earlier cTnI(sgx) algorithms. The prognostic composite end point was all-cause mortality and future nonfatal myocardial infarction during a median follow-up of 723 days. non-ST-segment-elevation myocardial infarction prevalence was 13%. The novel cTnI(sgx) algorithms showed similar performance regardless of time from symptom onset, and area under the curve was significantly better than comparators. The cTnI(sgx)0/1 hour algorithm classified 92% of patients to rule-in or rule-out compared with ≤78% of comparators. Patients allocated to rule-out by the prior published 0/1 hour algorithms had significantly fewer long-term events compared with the rule-in and observation groups. The novel cTnI(sgx)0/1 hour algorithm used a higher troponin baseline concentration for rule-out and did not allow for prognostication. Conclusions Increasingly sensitive troponin assays may improve identification of non-ST-segment-elevation myocardial infarction but could rule-out patients with subclinical chronic myocardial injury. Separate protocols for diagnosis and risk prediction seem appropriate