Rationale and design of ENDEAVOR: A sequential phase 2b-3 randomized clinical trial to evaluate the effect of myeloperoxidase inhibition on symptoms and exercise capacity in heart failure with preserved or mildly reduced ejection fraction.

AIMS: Mitiperstat (formerly AZD4831) is a novel selective myeloperoxidase inhibitor. Currently, no effective therapies target comorbidity-induced systemic inflammation, which may be a key mechanism underlying heart failure with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). Circulating neutrophils secrete myeloperoxidase, causing oxidative stress, microvascular endothelial dysfunction, interstitial fibrosis, cardiomyocyte remodelling and diastolic dysfunction. Mitiperstat may therefore improve function of the heart and other organs, and ameliorate heart failure symptoms and exercise intolerance. ENDEAVOR is a combined, seamless phase 2b-3 study of the efficacy and safety of mitiperstat in patients with HFpEF/HFmrEF. METHODS: In phase 2b, approximately 660 patients with heart failure and ejection fraction >40% are being randomized 1:1:1 to mitiperstat 2.5 mg, 5 mg or placebo for 48 weeks. Eligible patients have baseline 6-min walk distance (6MWD) of 30-400 m with a <50 m difference between screening and randomization and Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS) ≤90 points at screening and randomization. The dual primary endpoints are change from baseline to week 16 in 6MWD and KCCQ-TSS. The sample size provides 85% power to detect placebo-adjusted improvements of 21 m in 6MWD and 6.0 points in KCCQ-TSS at overall two-sided alpha of 0.05. Safety is monitored throughout treatment, with a focus on maculopapular rash. In phase 3 of ENDEAVOR, approximately 820 patients will be randomized 1:1 to mitiperstat or placebo. CONCLUSION: ENDEAVOR is the first phase 2b-3 study to evaluate whether myeloperoxidase inhibition can improve symptoms and exercise capacity in patients with HFpEF/HFmrEF.

Effect of AZD9977 and spironolactone on serum potassium in heart failure with preserved or mildly reduced ejection fraction, and renal impairment: A randomized trial.

This phase Ib study compared the effects of AZD9977, a selective mineralocorticoid receptor modulator with predicted low hyperkalemia risk, with spironolactone on serum potassium (sK+ ) in patients with heart failure (HF) with preserved or mildly reduced ejection fraction (EF; ≥40%), and renal impairment. Patients with HF with EF greater than or equal to 40% and estimated glomerular filtration rate of 40-70 ml/min/1.73 m2 were randomized to once-daily AZD9977 100 mg or spironolactone 25 mg for 14 days, up-titrated to AZD9977 200 mg or spironolactone 50 mg for another 14 days. The primary end point was relative change (%) in sK+ for AZD9977 versus spironolactone (baseline to day 28). Serum/urinary electrolytes, fractional excretion (FE) of Na+ /K+ , plasma aldosterone, cortisol, and renin, and safety were also assessed. Sixty-eight patients were randomized (AZD9977, n = 33; spironolactone, n = 35). Mean (SD) age was 73.0 (8.5) years, 51.5% men. Mean sK+ change from baseline to day 28 was 5.7% (AZD9977) and 4.2% (spironolactone), and 1.5% and 4.2% at day 14. Relative change (95% confidence interval) in sK+ with AZD9977 versus spironolactone was -0.3% (-5.3% to 4.4%; day 28), and 3.4% (-0.8% to 7.5%; day 14). Median increase from baseline in plasma aldosterone at day 28 was 89.8 pmol/L for AZD9977 and 67.4 pmol/L for spironolactone. Median FE of K+ was 12.9% (AZD9977) and 10.1% (spironolactone). AZD9977 was well-tolerated. No discontinuations due to hyperkalemia occurred with either treatment. Evidence of target engagement for AZD9977 with a favorable safety profile, supports further evaluation of AZD9977 in patients with HF and renal impairment.

A Meta-Analysis of the Efficacy of Behavioral Interventions to Reduce Risky Sexual Behavior and Decrease Sexually Transmitted Infections in Latinas Living in the United States.

The objective of this meta-analysis was to determine the effect of behavioral interventions in reducing risky sexual behavior and incident sexually transmitted infections (STI) among Latina women living in the United States. Studies were found by systematically searching the MEDLINE, EMBASE, and PsychInfo databases without language restriction. Two independent reviewers screened abstracts and full texts of articles to find randomized control trials testing the effects of behavioral interventions aimed at changing risky sexual behavior among Latinas. Articles were selected using prespecified inclusion criteria. Two independent reviewers extracted data from the included trials in duplicate using a standardized data extraction form. Six randomized control trials met the inclusion criteria for a total of 2,909 participants. Using random effects models with inverse variance weighting, we found a protective effect of the behavioral intervention on reported risky sexual behavior (odds ratio = 0.52; 95% confidence interval = 0.42, 0.64) and on incident nonviral STI (odds ratio = 0.65; 95% confidence interval = 0.46, 0.93). Behavioral interventions targeted toward Latina populations are effective in reducing risky sexual behaviors and incident STI and should be considered by policymakers as a potential tool for HIV/STI prevention in this population.

Investigating cancer clusters in Louisiana and interpreting results.

Physicians are often asked questions related to cancer frequency in their communities, particularly in Louisiana because of the perception of high cancer rates in this region. When individuals perceive a higher than normal rate of cancer in their geographic area, time frame, or group of people, questions about the potential role of environmental contamination are often raised. The purpose of this article is to educate clinicians about the concept of cancer clusters so they can further disseminate this knowledge to patients concerned about increased cancer frequency in their communities. This article will accomplish this goal through the consideration of potential questions or concerns patients might present related to cancer frequency in their communities.

A family cluster of tuberculosis cases, including a case of acquired multidrug resistant tuberculosis.

Although the number of tuberculosis cases in the US is at an all-time low, with progressive declines seen for the past 17 years, many goals in the tuberculosis elimination process remain unrealized. This report describes a cluster of four tuberculosis cases in a family, including one case of acquired multidrug resistant tuberculosis. It also underscores some important issues in tuberculosis control today, including significant disparities in the foreign-born population with multidrug resistant tuberculosis as a looming problem, as well as utilization of therapeutic drug level monitoring in complicated cases.

Increase in primary and secondary syphilis cases in older adults in Louisiana.

Sexually active young adults and adolescents experience a majority of the burden of sexually transmitted diseases in the United States and public health resources are appropriately directed at these age groups. However, sexual health of older adults is often ignored. An analysis of sexually transmitted disease surveillance data from the Louisiana Office of Public Health show that both the numbers and rates of primary and secondary syphilis cases have increased in older age groups over the past 10 years. Clinicians must be aware of increased use of erectile dysfunction drugs in older persons as a possible risk factor for sexually transmitted diseases. Clinicians must also realize that a significant number of older persons display sexually risky behavior and safe sexual health counseling is often overlooked in this population.

How can we improve the nursing work environment?

It has been suggested by many recently that the nursing work environment needs to be altered to make it more responsive to both nurse and patient needs. One essential aspect of this change would be to increase patient safety. This article suggests that to improve patient safety as well as satisfaction of nurses, the culture of the nursing organization should be transformed into one of a "learning organization." Using this model of an organization, every member of the nursing organization would be encouraged to reach his or her greatest potential, the welfare of the team would become paramount, and a shared vision of where the organization needs to go would emerge, thus maximizing productivity, safety, and job satisfaction for all healthcare team members. This transformation could mean that the terms "Nursing Organizations" and "Learning Organizations" would not have to be oxymorons.