A phase 3 study evaluating the lot consistency, immunogenicity, safety, and tolerability of a Clostridioides difficile vaccine in healthy adults 65 to 85 years of age.

BACKGROUND: A toxoid-based Clostridioides difficile vaccine is currently in development. Here, we report lot-to-lot consistency, immunogenicity, safety, and tolerability of 3 C difficile vaccine doses in healthy older adults. METHODS: This phase 3, placebo-controlled study randomized (1:1:1:1) healthy adults 65 to 85 years of age to 1 of 3 C difficile vaccine lots or placebo. Participants received C difficile vaccine (200 µg total toxoid) or placebo (Months 0, 1, 6). The primary immunogenicity objective was lot-to-lot consistency (2-sided 95 % CIs within 0.5 and 2 for comparisons of geometric mean concentration [GMC] ratios) for toxins A- and B-specific neutralizing antibody levels 1 month after Dose 3. Safety outcomes included local reactions and systemic events ≤7 days after vaccination, adverse events (AEs), and serious AEs (SAEs). RESULTS: Of 1317 enrolled participants, 1218 completed the study. C difficile vaccine immunogenicity was consistent across lots, with neutralizing antibody responses 1 month after Dose 3 for both toxin A (GMC [95 % CI]: lot 1, 878.8 [786.3, 982.2]; lot 2, 873.0 [779.2, 978.1]; lot 3, 872.9 [782.6, 973.5]) and toxin B (lot 1, 5823.9 [5041.0, 6728.4]; lot 2, 5462.8 [4733.4, 6304.7]; lot 3, 5426.0 [4724.4, 6231.8]). Two-sided 95 % CIs for GMC ratios were within 0.5 and 2 for toxins A and B, indicating lot-to-lot consistency was achieved. C difficile vaccine was well tolerated, with similar rates of local reactions and systemic events among vaccine lots. AE and SAE rates were similar across C difficile vaccine (36.5 % and 4.5 %, respectively) and placebo (35.3 % and 6 %). CONCLUSIONS: Three doses (Months 0,1,6) of toxoid-based C difficile vaccine induced robust neutralizing antibody responses and were well tolerated in healthy participants 65 to 85 years of age. Lot-to-lot consistency was excellent, indicating the manufacturing process for this C difficile vaccine formulation was well controlled. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03579459.

Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) infection causes considerable illness in older adults. The efficacy and safety of an investigational bivalent RSV prefusion F protein-based (RSVpreF) vaccine in this population are unknown. METHODS: In this ongoing, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults (≥60 years of age) to receive a single intramuscular injection of RSVpreF vaccine at a dose of 120 µg (RSV subgroups A and B, 60 µg each) or placebo. The two primary end points were vaccine efficacy against seasonal RSV-associated lower respiratory tract illness with at least two or at least three signs or symptoms. The secondary end point was vaccine efficacy against RSV-associated acute respiratory illness. RESULTS: At the interim analysis (data-cutoff date, July 14, 2022), 34,284 participants had received RSVpreF vaccine (17,215 participants) or placebo (17,069 participants). RSV-associated lower respiratory tract illness with at least two signs or symptoms occurred in 11 participants in the vaccine group (1.19 cases per 1000 person-years of observation) and 33 participants in the placebo group (3.58 cases per 1000 person-years of observation) (vaccine efficacy, 66.7%; 96.66% confidence interval [CI], 28.8 to 85.8); 2 cases (0.22 cases per 1000 person-years of observation) and 14 cases (1.52 cases per 1000 person-years of observation), respectively, occurred with at least three signs or symptoms (vaccine efficacy, 85.7%; 96.66% CI, 32.0 to 98.7). RSV-associated acute respiratory illness occurred in 22 participants in the vaccine group (2.38 cases per 1000 person-years of observation) and 58 participants in the placebo group (6.30 cases per 1000 person-years of observation) (vaccine efficacy, 62.1%; 95% CI, 37.1 to 77.9). The incidence of local reactions was higher with vaccine (12%) than with placebo (7%); the incidences of systemic events were similar (27% and 26%, respectively). Similar rates of adverse events through 1 month after injection were reported (vaccine, 9.0%; placebo, 8.5%), with 1.4% and 1.0%, respectively, considered by the investigators to be injection-related. Severe or life-threatening adverse events were reported in 0.5% of vaccine recipients and 0.4% of placebo recipients. Serious adverse events were reported in 2.3% of participants in each group through the data-cutoff date. CONCLUSIONS: RSVpreF vaccine prevented RSV-associated lower respiratory tract illness and RSV-associated acute respiratory illness in adults (≥60 years of age), without evident safety concerns. (Funded by Pfizer; RENOIR ClinicalTrials.gov number, NCT05035212; EudraCT number, 2021-003693-31.).

Overcoming barriers to the adoption and implementation of predictive modeling and machine learning in clinical care: what can we learn from US academic medical centers?

There is little known about how academic medical centers (AMCs) in the US develop, implement, and maintain predictive modeling and machine learning (PM and ML) models. We conducted semi-structured interviews with leaders from AMCs to assess their use of PM and ML in clinical care, understand associated challenges, and determine recommended best practices. Each transcribed interview was iteratively coded and reconciled by a minimum of 2 investigators to identify key barriers to and facilitators of PM and ML adoption and implementation in clinical care. Interviews were conducted with 33 individuals from 19 AMCs nationally. AMCs varied greatly in the use of PM and ML within clinical care, from some just beginning to explore their utility to others with multiple models integrated into clinical care. Informants identified 5 key barriers to the adoption and implementation of PM and ML in clinical care: (1) culture and personnel, (2) clinical utility of the PM and ML tool, (3) financing, (4) technology, and (5) data. Recommendation to the informatics community to overcome these barriers included: (1) development of robust evaluation methodologies, (2) partnership with vendors, and (3) development and dissemination of best practices. For institutions developing clinical PM and ML applications, they are advised to: (1) develop appropriate governance, (2) strengthen data access, integrity, and provenance, and (3) adhere to the 5 rights of clinical decision support. This article highlights key challenges of implementing PM and ML in clinical care at AMCs and suggests best practices for development, implementation, and maintenance at these institutions.

Acceptability and Feasibility of Human Papilloma Virus Self-Sampling for Cervical Cancer Screening.

OBJECTIVES: Women in safety-net institutions are less likely to receive cervical cancer screening. Human papilloma virus (HPV) self-sampling is an alternative method of cervical cancer screening. We examine the acceptability and feasibility of HPV self-sampling among patients and clinic staff in two safety-net clinics in Miami. MATERIALS AND METHODS: Haitian and Latina women aged 30-65 years with no Pap smear in the past 3 years were recruited. Women were offered HPV self-sampling or traditional Pap smear screening. The acceptability of HPV self-sampling among patients and clinic staff was assessed. If traditional screening was preferred the medical record was reviewed. RESULTS: A total of 180 women were recruited (134 Latinas and 46 Haitian). HPV self-sampling was selected by 67% women. Among those selecting traditional screening, 22% were not screened 5 months postrecruitment. Over 80% of women agreed HPV self-sampling was faster, more private, easy to use, and would prefer to use again. Among clinic staff, 80% agreed they would be willing to incorporate HPV self-sampling into practice. CONCLUSIONS: HPV self-sampling was both acceptable and feasible to participants and clinic staff and may help overcome barriers to screening.

Breast Health Disparities: A Primer for Medical Students.

INTRODUCTION: While breast cancer incidence rates have remained stable and mortality rates have declined for white women, breast cancer mortality has steadily increased for African American women since the 1950s. It has often been assumed that genetic risks linked to African ancestry are the cause for these disparities. However, a better understanding of the role of stress and social and environmental factors in health lends evidence to the social determinants behind the increasing gaps in breast health outcomes. This resource's goal is to raise awareness among undergraduate medical students about breast cancer disparities, particularly the late-stage diagnoses and the higher mortality rate for African American women. METHODS: Our educational session included a lecture on basic epidemiological data and information on breast cancer etiology followed by a case study, which was created with the founder of a local cancer support and resource center serving mainly African American women diagnosed with breast cancer. As part of the case exercise, we utilized concept mapping as a tool to apply learning. RESULTS: Pre-/postquizzes showed significant improvements in knowledge and confidence in working with patients. Narrative reflections from students indicated an improvement in targeting at-risk populations, educating patients about their risk and options, and understanding the complex role that socioeconomic factors may play in patient outcomes. DISCUSSION: By raising awareness and exposing medical students to the socioeconomic and cultural aspects of breast health, we hope to improve medical students' knowledge of risk factors and preventive strategies, as well as their abilities to guide patients through appropriate screening and follow-up.

Is greater acculturation associated with an increased prevalence of cardiovascular risk factors among Latinos in South Florida?

OBJECTIVE: To examine the association of acculturation with various cardiovascular risk factors (CRFs) among Latinos with diabetes in South Florida. METHODS: In a cross-sectional analysis of data collected from 300 Latinos with poorly controlled diabetes we measured acculturation using the Marin Short Acculturation Scale. We examined correlations between acculturation and the following 7 CRFs: hemoglobin A1C, low-density lipoprotein, systolic blood pressure, body mass index, smoking status, physical activity, and fruit and vegetable intake. RESULTS: Cubans made up 38% of our population; no other Latino subgroup represented over 17% of the sample. Of the 8 outcomes examined, only smoking was associated with increased acculturation; 12% of Latinos in the 2 lowest acculturation groups were current smokers versus 25% in the highest acculturation group (P=0.02). Furthermore, Cuban Americans from our sample had over double the prevalence of smoking compared with non-Cubans in both the lowest and highest acculturation groups. CONCLUSIONS: With the exception of smoking, our data does not support a link between increased acculturation and higher prevalence of CRFs in Latinos with diabetes. Smoking prevention and cessation programs targeting Latinos and particularly among Cubans are needed.

Rationale and design of the research project of the South Florida Center for the Reduction of Cancer Health Disparities (SUCCESS): study protocol for a randomized controlled trial.

BACKGROUND: In the United States certain minority groups, such as racial/ethnic immigrant women, are less likely than non-Hispanic White women to be screened for cervical cancer. Barriers to such care include health insurance, cost, knowledge, attitudes, health literacy, and cultural norms and practices. Among the most promising approaches to increase screening in these groups are patient navigators that can link women to sources of appropriate care. Another recent promising approach is using human papilloma virus (HPV) self-sampling. In this manuscript, we describe our National Cancer Institute-sponsored study testing such approaches among immigrant minority women. DESIGN: The South Florida Center for the Reduction of Cancer Health Disparities (SUCCESS) is conducting a three-arm randomized trial among Hispanic, Haitian, and African American women in Miami-Dade County. Community health workers (CHW) based in each of three communities are recruiting 200 women at each site (600 total). Eligibility criteria include women aged 30-65 years who have not had a Pap smear test in the last 3 years. Prior to randomization, all women undergo a standardized structured interview. Women randomized to public health outreach, Group 1, receive culturally tailored educational materials. Women in Group 2 receive an individualized comprehensive cervical cancer CHW-led education session followed by patient navigation to obtain the Pap smear test at community-based facilities. Women in Group 3 have the option of navigation to a Pap smear test or performing HPV self-sampling. The primary outcome is self-report of completed screening through a Pap smear test or HPV self-sampling within 6 months after enrollment. DISCUSSION: SUCCESS is one of the first trials testing HPV self-sampling as a screening strategy among underserved minority women. If successful, HPV self-sampling may be an important option in community outreach programs aimed at reducing disparities in cervical cancer. TRIAL REGISTRATION: Clinical Trials.gov # NCT02121548, registered April 21, 2014.

Epidemiology and outcomes of out-of-hospital cardiac arrest in Rochester, New York.

OBJECTIVE: To characterize out-of-hospital cardiac arrest (OHCA) and factors that affect survival in a medium sized city that uses system status management for dispatch. METHODS: A retrospective cohort study of all adult OHCA patients treated by EMS between 1998 and 2001 was conducted using Utstein definitions. The primary endpoint was 1-year survival. RESULTS: Of the 1177 patients who experienced OHCA during the study period, 539 (46%) met inclusion criteria. Age ranged from 18 to 98 years (median 67). The median call-response interval was 5 min (range 0-21), and 93% were 9 min or less. There was no significant difference in the median call-response intervals between call location zip (Post) codes (p=0.07). Twenty percent of experienced ROSC (95% CI 17-23), 7% survived more than 30 days (95% CI 5-9%), and 5% survived to 1 year (95% CI 3-7%). In bivariate analysis, first rhythm and bystander CPR affected survival to 1 year. There was no significant difference in survival between male (4%) and female (7%), black (4%) and white (6%), or witnessed (7%) and unwitnessed arrest (4%). Logistic regression identified younger age, CPR initiated by bystander (19%) or first responder (41%), and presenting rhythm of VF/VT (32%) as factors associated with survival to 1 year. CONCLUSIONS: This study finds a 5% survival to 1 year among OHCA patients in Rochester, NY. A presenting rhythm of VF/VT and bystander CPR were associated with increased survival.