Sweat chloride reflects CFTR function and correlates with clinical outcomes following CFTR modulator treatment.

Background: Highly effective CFTR modulators improve CFTR function and lead to dramatic improvements in health outcomes in many people with cystic fibrosis (pwCF). The relationship between measures of CFTR function, such as sweat chloride concentration, and clinical outcomes in pwCF treated with CFTR modulators is poorly defined. We conducted analyses to better understand the relationships between sweat chloride and CFTR function in vitro, and between sweat chloride and clinical outcomes following CFTR modulator treatment.

Case Report: A delicate equilibrium of exocrine pancreatic recovery and hepatotoxicity with elexacaftor/tezacaftor/ivacaftor therapy in a pediatric patient with cystic fibrosis.

This case report presents a comprehensive evaluation of the complex balance of therapeutic benefits and potential risks associated with the cystic fibrosis transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (ETI) therapy in managing an eight-year-old male with cystic fibrosis (CF) and exocrine pancreatic insufficiency (EPI). While ETI therapy significantly enhanced exocrine pancreatic function, it led to hepatotoxicity, necessitating therapy discontinuation. Attempts to restart ETI at reduced doses were unsuccessful due to persistent hepatic dysfunction.

Equity-Focused Evaluation of a Medicaid-Funded Statewide Diabetes Quality Improvement Project Collaborative.

Objective: To evaluate the Ohio Diabetes Quality Improvement Project (QIP) equity aim to reduce the percentage of Non-Hispanic Black (NHB) and Hispanic patients with A1C >9% by ≥20% over 2 years.

Research Design And Methods: The Ohio Department of Medicaid, Ohio Colleges of Medicine Government Resource Center, Ohio Medicaid managed care plans, and seven medical schools in Ohio formed the Diabetes QIP collaborative using the collective impact model to improve diabetes outcomes and equity in 20 practices across 11 health systems. The quality improvement (QI) strategies included data audit and feedback, peer-to-peer learning, QI coaching/practice facilitation, and subject matter expert consultation through coaching calls, monthly webinars, and annual virtual learning sessions.

The continuing need for dornase alfa for extracellular airway DNA hydrolysis in the era of CFTR modulators.

Introduction: The availability of cystic fibrosis transmembrane conductance regulator (CFTR) modulators opens the possibility of discontinuing some chronic pulmonary therapies to decrease cystic fibrosis (CF) treatment burden. However, CFTR modulators may not adequately address neutrophilic inflammation, which contributes to a self-perpetual cycle of viscous CF sputum, airway obstruction, inflammation, and lung function decline.

Areas Covered: This review discusses the emerging role of neutrophil extracellular traps in CF and its role in CF sputum viscosity, airway obstruction, and inflammation, based on a literature search of PubMed (1990-present).

Efficacy and safety of LAU-7b in a Phase 2 trial in adults with cystic fibrosis.

Background: Lung inflammation is associated with tissue damage in cystic fibrosis (CF). LAU-7b, a novel oral drug candidate, was shown to control inflammation and stabilize CFTR protein in the epithelial membrane during inflammatory stress in preclinical models of CF.

Methods: A double-blind, randomized, placebo-controlled Phase 2 study was conducted to evaluate efficacy and safety of LAU-7b in adults with CF.

Assessing Priorities in a Statewide Cardiovascular and Diabetes Health Collaborative Based on the Results of a Needs Assessment: Cross-Sectional Survey Study.

Background: The Ohio Cardiovascular and Diabetes Health Collaborative (Cardi-OH) unites general and subspecialty medical staff at the 7 medical schools in Ohio with community and public health partnerships to improve cardiovascular and diabetes health outcomes and eliminate disparities in Ohio's Medicaid population. Although statewide collaboratives exist to address health improvements, few deploy needs assessments to inform their work.

Objective: Cardi-OH conducts an annual needs assessment to identify high-priority clinical topics, screening practices, policy changes for home monitoring devices and referrals, and preferences for the dissemination and implementation of evidence-based best practices.

Effects of the Communities that Heal (CTH) intervention on perceived opioid-related community stigma in the HEALing Communities Study: results of a multi-site, community-level, cluster-randomized trial.

Background: Community stigma against people with opioid use disorder (OUD) and intervention stigma (e.g., toward naloxone) exacerbate the opioid overdose crisis.

Impact of the Communities That HEAL Intervention on Buprenorphine-Waivered Practitioners and Buprenorphine Prescribing: A Prespecified Secondary Analysis of the HCS Randomized Clinical Trial.

Importance: Buprenorphine significantly reduces opioid-related overdose mortality. From 2002 to 2022, the Drug Addiction Treatment Act of 2000 (DATA 2000) required qualified practitioners to receive a waiver from the Drug Enforcement Agency to prescribe buprenorphine for treatment of opioid use disorder. During this period, waiver uptake among practitioners was modest; subsequent changes need to be examined.

Heterogeneity of CFTR modulator-induced sweat chloride concentrations in people with cystic fibrosis.

Background: Sweat chloride (SC) concentrations in people with cystic fibrosis (PwCF) reflect relative CF transmembrane conductance regulator (CFTR) protein function, the primary CF defect. Populations with greater SC concentrations tend to have lesser CFTR function and more severe disease courses. CFTR modulator treatment can improve CFTR function within specific CF genotypes and is commonly associated with reduced SC concentration.

A Medicaid-Funded Statewide Diabetes Quality Improvement Collaborative: Ohio 2020‒2022.

We used a collective impact model to form a statewide diabetes quality improvement collaborative to improve diabetes outcomes and advance diabetes health equity. Between 2020 and 2022, in collaboration with the Ohio Department of Medicaid, Medicaid Managed Care Plans, and Ohio's seven medical schools, we recruited 20 primary care practices across the state. The percentage of patients with hemoglobin A1c greater than 9% improved from 25% to 20% over two years.

Longitudinal bacterial prevalence in cystic fibrosis airways: Fact and artifact.

Background: Opportunistic bacterial infection is a hallmark of cystic fibrosis (CF) lung disease and early mortality. Poorly characterized prevalence changes have accompanied two decades of health improvements, with CFTR modulators likely to further affect infection epidemiology.

Methods: Bacterial prevalence change trends across birth cohorts were assessed with linear regression using 2001-2019 US CF Foundation Patient Registry data.

Advancing the pipeline of cystic fibrosis clinical trials: a new roadmap with a global trial network perspective.

The growing use of modulator therapies aimed at restoring cystic fibrosis transmembrane conductance regulator (CFTR) protein function in people with cystic fibrosis has fundamentally altered clinical trial strategies needed to advance new therapeutics across an orphan disease population that is now divided by CFTR modulator eligibility. The development of a robust pipeline of nucleic acid-based therapies (NABTs)-initially directed towards the estimated 10% of the cystic fibrosis population who are genetically ineligible for, or intolerant of, CFTR modulators-is dependent on the optimisation of restricted trial participant resources across multiple development programmes, a challenge that will preclude the use of gold standard placebo-controlled trials. Advancement of a full pipeline of symptomatic therapies across the entire cystic fibrosis population will be challenged by smaller effect sizes and uncertainty regarding their clinical importance in a growing modulator-treated population with more mild and stable pulmonary disease.

Willingness of people with cystic fibrosis receiving elexacaftor/tezacaftor/ivacaftor (ETI) to participate in randomized modulator and inhaled antimicrobial clinical trials.

Objective: To assess the feasibility of enrolling people with CF (pwCF) taking the CFTR modulator elexacaftor/tezacaftor/ivacaftor (ETI) in clinical trials of a new modulator.

Methods: PwCF receiving ETI at CHEC-SC study (NCT03350828) enrollment were surveyed for interest in 2-week to 6-month placebo- (PC) and active-comparator (AC) modulator studies. Those taking inhaled antimicrobials (inhABX) were surveyed for interest in PC inhABX studies.

A Medicaid Statewide Hypertension Quality Improvement Project: Initial Results.

Background Hypertension control is critical to reducing cardiovascular disease, challenging to achieve, and exacerbated by socioeconomic inequities. Few states have established statewide quality improvement (QI) infrastructures to improve blood pressure (BP) control across economically disadvantaged populations. In this study, we aimed to improve BP control by 15% for all Medicaid recipients and by 20% for non-Hispanic Black participants.

Rate of Lung Function Decline in People with Cystic Fibrosis Having a Residual Function Gene Mutation.

Introduction: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Approximately 5% of people with CF have residual function (RF) CFTR mutations that result in partially retained CFTR activity. Published literature on disease trajectory among those with RF mutations is limited.

Forming Cardi-OH: A Statewide Collaborative to Improve Cardiovascular Health in Ohio.

Background Cardiovascular risk factor control is challenging, especially in disadvantaged populations. However, few statewide efforts exist to tackle this challenge. Therefore, our objective is to describe the formation of a unique statewide cardiovascular health collaborative so others may learn from this approach.

Characterizing CFTR modulated sweat chloride response across the cf population: Initial results from the CHEC-SC study.

Background: CHEC-SC is an ongoing epidemiologic study characterizing modulator-induced sweat chloride (SC) responses across the CF population, with interim results available prior to the availability of triple combination modulator therapy.

Methods: Eligible participants had been prescribed a modulator for ≥90 days with re-enrollment allowed upon establishment of a new modulator. Pre-modulator SC values were obtained from chart review; post-modulator sweat was collected and analyzed locally.

Increasing life expectancy in cystic fibrosis: Advances and challenges.

Since the first description of cystic fibrosis in 1938, there have been significant advances in both quality of life and longevity for people living with this disease. In this article we describe the milestones of the last 80 years and what we perceive to be the remaining barriers to normalcy for this population.

Empire-CF study: A phase 2 clinical trial of leukotriene A4 hydrolase inhibitor acebilustat in adult subjects with cystic fibrosis.

Background: Cystic fibrosis (CF) is characterized by neutrophilic inflammation in the airways. Leukotriene B4 (LTB) is a neutrophil chemoattractant and has been implicated in CF pathogenesis. Acebilustat, a novel, synthetic, small-molecule leukotriene A4 hydrolase inhibitor, reduces LTB production.

Disease burden in people with cystic fibrosis heterozygous for F508del and a minimal function mutation.

Background: People with cystic fibrosis (CF) heterozygous for F508del-CFTR and a minimal function CFTR mutation (F/MF) that results in no CFTR protein or results in CFTR protein that is not responsive to tezacaftor, ivacaftor, and tezacaftor/ivacaftor in vitro comprise a sizeable percentage of the US CF population. This retrospective, cross-sectional, observational study aimed to characterize CF burden in this subpopulation.

Methods: People ≥2 years of age in the US CF Foundation Patient Registry with a CF diagnosis, F/MF genotype, and ≥1 encounters in 2017 were included.

Long-term amikacin liposome inhalation suspension in cystic fibrosis patients with chronic P. aeruginosa infection.

Background: . In CLEAR-108-a phase 3, randomised, open-label study-once-daily amikacin liposome inhalation suspension (ALIS) was noninferior to twice-daily tobramycin inhalation solution (TIS) in improving lung function in patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa infection after 3 treatment cycles (28 days on/28 days off). The CLEAR-110 extension study (ClinicalTrials.