Disparities in the Timeliness of Addressing Patient-Initiated Telephone Calls in a Primary Care Clinic: The Impact of Quality Improvement Interventions.

A timely response to patient-initiated telephone calls can affect many aspects of patient health, including quality of care and health equity. Historically, at a family medicine residency clinic, at least 1 out of 4 patient calls remained unresolved three days after the call was placed. We sought to explore whether there were differential delays in resolution of patient concerns for certain groups and how these were affected by quality improvement interventions to increase responsiveness to patient calls. A multidisciplinary team at a primary care residency clinic applied Lean education and tools to improve the timeliness of addressing telephone encounters. Telephone encounter data were obtained for one year before and nine months after the intervention. Data were stratified by race, ethnicity, preferred language, sex, online portal activation status, age category, zip code, patient risk category, and reason for call. Stratified data revealed consistently worse performance on telephone encounter closure by 72 hours for Black/African American patients compared to Hispanic and non-Hispanic White patients pre-intervention. Interventions resulted in statistically significant overall improvement, with an OR of 2.9 (95% CI: 2.62 to 3.21). Though interventions did not target a specific population, pre-intervention differences based on race and ethnicity resolved post-intervention. Telephone calls serve as an important means of patient communication with care teams. General interventions to improve the timeliness of addressing telephone encounters can lead to sustainable improvement in a primary care academic clinic and may also alleviate disparities.

Safety and Immunogenicity of Influenza A/H5N8 Virus Vaccine in Healthy Adults: Durability and Cross-reactivity of Antibody Responses.

BACKGROUND: Influenza A/H5N8 viruses infect poultry and wild birds in many countries. In 2021, the first human A/H5N8 cases were reported. METHODS: We conducted a phase I, cohort-randomized, double-blind, controlled trial of inactivated influenza A/H5N8 vaccine (clade 2.3.4.4c) administered with or without adjuvant. Cohort 1 subjects received either two doses of AS03-adjuvanted vaccine containing 3.75 µg or 15 µg hemagglutinin (HA); two doses of 15 µg HA unadjuvanted vaccine; or one dose of AS03-adjuvanted vaccine (3.75 µg or 15 µg HA), followed by one dose of non-adjuvanted vaccine (same HA content). Cohort 2 subjects received two doses of MF59-adjuvanted vaccine containing 3.75 µg or 15 µg HA, or 15 µg HA of non-adjuvanted vaccine. Subjects were followed for 13 months for safety and immunogenicity. RESULTS: We enrolled 386 adult subjects in good health. Solicited adverse events were generally mild and more common among subjects who received adjuvanted vaccines. Antibody responses (hemagglutination inhibition or microneutralization assays) were highest in the two-dose AS03 group, followed by the one-dose AS03 group, the MF59 groups, and the non-adjuvanted groups. Antibody levels returned to baseline 12 months after the second vaccination in all groups except the 15 µg AS03-adjuvanted group. Cross-reactive antibodies to clade 2.3.4.4b strains isolated from recent human cases were demonstrated in a subset of both 15 µg adjuvanted groups. CONCLUSIONS: Two doses of influenza A/H5N8 vaccine were well-tolerated. Immunogenicity improved with receipt of two doses of adjuvanted vaccine and higher antigen content. (Funded by the National Institute of Allergy and Infectious Diseases.

"When the Bills Keep on Coming:" the Experiences of Seafood Processors During the COVID-19 Pandemic.

Essential workers were at increased risk during the COVID-19 pandemic, including seafood processors who are often rendered invisible within the public sphere. To examine the health and safety concerns of seafood processors, many who are low income or im/migrant workers on H-2B visas, our team conducted qualitative research with 44 participants. We found that in addition to high occupational health hazards that existed before the pandemic, COVID-19 increased workers' financial risks, which put them in more dangerous health and safety positions, since they needed to work through physical and mental health illness. These financial risks can be seen through the themes of paid sick leave, mental health, economic duress, and primary care access. We conclude with three recommendations to the H-2B visa worker program, which will not only decrease health disparities for im/migrant workers, but also increase health equity across seafood worker populations.

Does hormone therapy exacerbate other venous thromboembolism risk factors?

OBJECTIVE: Postmenopausal symptoms in women at higher risk for venous thromboembolism (VTE) due to comorbidities are often undertreated because of concerns that hormone therapy (HT) may increase VTE risk; however, it is unclear how much HT impacts risk of VTE when compared with other risk factors. METHODS: This is a case-control study in a commercial claims database from 2007 to 2019. Women aged 50 to 64 years (n = 223,949) were classified as cases if they had an International Classification of Diseases code indicating an acute VTE plus a filled prescription for an anticoagulant, placement of intravascular vena cava filter, or death within 30 days of diagnosis. Controls were matched 10:1 to each case by index date and age. Risk factors and comorbidities present within the year before index were examined. Exposure was defined as a HT prescription within 60 days before index. RESULTS: There were 20,359 VTE cases and 203,590 matched controls. A conditional logistic regression indicated that the greatest risks for VTE were from metastatic cancer (odds ratio [OR], 13.66; 95% CI, 12.64-14.75), hospitalization/surgery (OR, 8.51; 95% CI, 8.09-8.96), trauma (OR, 3.52; 95% CI, 3.32-3.73), comorbidity burden (OR, 3.51; 95% CI, 3.34-3.69), history of hypercoagulable condition (OR, 3.10; 95% CI, 2.87-3.36), and varicose veins (OR, 2.87; 95% CI, 2.56-3.22). Regarding hormone exposure, we observed ORs of 1.51 (95% CI, 1.43-1.60) for any recent hormone exposure; 1.13 (95% CI, 1.04-1.23; number needed to harm, 4,274) for unopposed estrogen menopausal HT; 1.23 (95% CI, 1.10-1.38; number needed to harm, 2,440) for combined menopausal HT; and 5.22 (95% CI, 4.67-5.84) for combined hormonal contraceptives compared with no recent HT exposure. CONCLUSIONS: Hormone therapy exposure did not appear to adversely influence other risk factors, and exposure generally played a minor role in VTE risk. Contraceptives, however, were a strong risk factor.

Overcoming Mission Competition in Departments of Family Medicine.

Departments of family medicine are centered around the tripartite mission of education, research, and clinical care. Historically, these three missions have been balanced and interdependent; however, changes in the funding and structures of health systems have resulted in shrinking education and research missions and an increased emphasis on clinical care. In the wake of waning state and federal contributions to primary care research, many departments of family medicine have adopted a private practice approach. This approach is centered on generating revenue for the institution, incentivizing physicians to remain clinically focused through productivity and intense attention to volume targets. As a department's focus shifts to the clinical care mission, education and research are increasingly neglected and underresourced. Meanwhile, the administrative burden of electronic health records (EHRs) has further encroached on time previously allocated to research, with the EHR burden disproportionately affecting the primary care workforce. To counteract mission competition in departments of family medicine and to recover the vital missions of education and scholarship, devising a clear plan for reclaiming and sustaining a tripartite mission is important. Advocating for increased primary care research funding, enhancing EHRs, balancing clinical and education metrics, and supporting primary care research, especially for groups underrepresented in medicine, are interventions to help fully support education and research missions and to recover and sustain mission balance in departments of family medicine.

Family Medicine Team Perspectives on Screening for Health-Related Social Needs.

INTRODUCTION: Social drivers of health (SDH) strongly influence health outcomes and disparities. Although systemic level change is vital to address the disparities driven by SDH, it is also crucial that health care organizations develop the ability to care for patients in a manner that accounts for social factors and their influence on patient health. Although primary care is a natural fit for health-related social needs (HRSN) screening and intervention, significant barriers can impede primary care's effectiveness in this area. METHODS: We conducted 3 focus groups with family medicine clinicians, clinical staff, and social care workers in an academic medical center using a semistructured discussion guide to explore current practices, perceived benefits, barriers, and potential opportunities and approaches for integrating routine HRSN screening in primary care. RESULTS: 3 primary themes emerged from the focus groups. They included 1) the barriers to routine screening in primary care, including time, workload, emotional burden, patient factors, and team members' fear of inadequacy of resources or their own ability; 2) the importance and benefit of HRSN screening, including the opportunity to improve patient care through increased care team awareness of the patient's context, interventions to address HRSN, and improved relationships between the care team and the patient; and 3) recommendations for implementing routine screening in primary care, including opportunities to optimize workflow and technology, the importance of an electronic medical record (EMR)-integrated resource database, and the centrality of teamwork. DISCUSSION: Family medicine health care teams embrace the importance of HRSN screening and the potential for positive impact. However, there are vital barriers and considerations to address for HRSN screening to be effectively integrated into primary care visits.

A community health worker led diabetes self-management education program: Reducing patient and system burden.

AIMS: Conduct a secondary analysis of the TIME (Telehealth-supported, Integrated Community Health Workers (CHWs), Medication access, diabetes Education) made simple trial (SIMPLE) to evaluate healthcare utilization and explore variables that may have influenced HbA1c. METHODS: Participants (N = 134 [67/group]) were low-income, uninsured Hispanics with or at risk for type 2 diabetes mellitus. We included in-person and telehealth clinician visits, other visits, missed visits, orders placed, and guideline-adherence (e.g., vaccinations, quarterly HbA1c for uncontrolled diabetes). Using multivariable models, we explored for associations between HbA1c changes and these measures. RESULTS: The control arm had higher missed visits rates (intervention: 45 %; control: 56 %; p = 0.007) and missed telehealth appointments (intervention: 10 %; control: 27.4 %; p = 0.04). The intervention group received more COVID vaccinations than the control (p = 0.005). Other health measures were non-significant between groups. Intervention individuals' HbA1c improved with more missed visits (-0.60 %; p < 0.01) and worsened with improved guideline-adherent HbA1c measurements (HbA1c: 1.2 %; p = 0.057). The control group had non-significant HbA1c associations. CONCLUSIONS: Findings suggest that the SIMPLE trial's improved HbA1c levels stemmed from a CHW-driven intervention and not additional healthcare contact. Exploratory outcomes resulted in seemingly counterintuitive HbA1c associations with missed visits and guideline-adherent measurements; these may suggest that an intervention that enhances communication provides support to reduce the amount of follow-up needed by participants without sacrificing clinical improvements.

Preparing Community Health Workers to Empower Latino(a)s With Diabetes: A Real-World Implementation Study.

PURPOSE: The purpose of the study was to evaluate the delivery of diabetes self-management education (DSME) to Latino(a) adults by community health workers (CHWs). METHODS: Investigators developed an evidence-based, bilingual (Spanish/English) diabetes education curriculum and trained 10 CHWs on its content. CHWs then implemented the curriculum in 6-month diabetes group visit programs for low-income Latino(a)s with type 2 diabetes in nonacademic 501(c)3 community clinics. Investigators evaluated efficacy of the training through successful implementation, measured by participant group visit acceptance and attendance. RESULTS: Participants (n = 70) reported high levels of program satisfaction (3.8/4.0), improvement in quality of life (9.7/10), meeting of individual needs (3.8/4.0), and acceptability (9.7/10.0). Content analyses revealed that 87.1% of participants would not change the program or wanted to extend it. Participant attendance was 81.6%. CONCLUSIONS: Investigators demonstrated the ability to develop a training that nonmedical personnel (CHWs) successfully implemented in a real-world study. This study provides a curricular framework for CHW-led education that may serve as a template to extend to other diseases and populations.

Microbial determinants of dementia risk in subjects of Mexican descent with type 2 diabetes living in South Texas.

Type 2 diabetes (T2D) is a common forerunner of neurodegeneration and dementia, including Alzheimer's Disease (AD), yet the underlying mechanisms remain unresolved. Individuals of Mexican descent living in South Texas have increased prevalence of comorbid T2D and early onset AD, despite low incidence of the predisposing APOE-e4 variant and an absence of the phenotype among relatives residing in Mexico - suggesting a role for environmental factors in coincident T2D and AD susceptibility. Here, in a small clinical trial, we show dysbiosis of the human gut microbiome could contribute to neuroinflammation and risk for AD in this population. Divergent Gastrointestinal Symptom Rating Scale (GSRS) responses, despite no differences in expressed dietary preferences, provided the first evidence for altered gut microbial ecology among T2D subjects (sT2D) versus population-matched healthy controls (HC). Metataxonomic 16S rRNA sequencing of participant stool revealed a decrease in alpha diversity of sT2D versus HC gut communities and identified BMI as a driver of gut community structure. Linear discriminant analysis effect size (LEfSe) identified a significant decrease in the relative abundance of the short-chain fatty acid-producing taxa Lachnospiraceae, Faecalibacterium, and Alistipes and an increase in pathobionts Escherichia-Shigella, Enterobacter, and Clostridia innocuum among sT2D gut microbiota, as well as differentially abundant gene and metabolic pathways. These results suggest characterization of the gut microbiome of individuals with T2D could identify key actors among "disease state" microbiota which may increase risk for or accelerate the onset of neurodegeneration. Furthermore, they identify candidate microbiome-targeted approaches for prevention and treatment of neuroinflammation in AD.

Text messaging intervention for Pap smear uptake: a single-institution study.

Cervical cancer continues to be one of the leading causes of death among women in many parts of the world. With the increasing proliferation of mobile technology, text messaging interventions have been effective in improving Pap smear uptake in non-United States populations. This study evaluated whether text message reminders from a health system in Galveston, Texas, USA increased uptake of cervical cancer screening as compared to usual care. A single text message reminder was sent to 16,002 unique patient phone numbers using the Televox Communication Program from February 20, 2019, to April 4, 2019. The institution's population health database was subsequently used to determine if patients received cervical cancer screening (Pap smear) following the text message transmission. Patient demographics within text message and control groups were compared using Chi-square tests. Our text messaging intervention to improve Pap smear rates did not show a statistically significant difference between the intervention group receiving a text message and the control. However, there were significant interactions between text messages and age, financial class, and county (P=0.0023, 0.0299, and <0.0001, respectively). Text messaging did have a positive impact on our most vulnerable patient populations given that the text messaging intervention showed a marginally higher rate of Pap smear among Medicaid and low-income/uninsured (MLIU) patients. Text messaging interventions do have effectiveness in increasing Pap smear uptake in populations which are most impacted by health disparities.

Hormone exposure and venous thromboembolism in commercially insured women aged 50 to 64 years.

Background: Menopausal hormone therapy (MHT) can elevate venous thromboembolism (VTE) risk, but less is known about formulations and routes of exposures. Objective: To estimate hormone-associated VTE risk by route and formulation in exposed and unexposed women aged 50 to 64 years in the US. Methods: In a nested case-control study of US commercially insured women aged 50 to 64 years (2007-2019), cases were defined as incident VTE diagnoses and matched to 10 controls by date of VTE and age, excluding prior VTE, inferior vena cava filter placement, or anticoagulants. Filled prescriptions in the prior year defined hormone exposures. International Classification of Diseases and Current Procedural Terminology codes identified risk factors and comorbidities. Results: Odds ratios (ORs) were estimated with conditional logistic regression controlling for differences between cases (n = 20,359) and controls (n = 203,590) in comorbidities and VTE risk factors. For exposures within 60 days, oral MHT risk was almost twice as high as transdermal MHT (OR = 1.92; 95% CI, 1.43-2.60); transdermal MHT did not elevate risk compared with no exposure (unopposed OR = 0.70; 95% CI, 0.59-0.83; combined OR = 0.73; 95% CI, 0.56-0.96). Risk was highest for MHT combinations with ethinyl estradiol, followed by conjugated equine estrogen (CEE) (ethinyl estradiol-CEE: OR = 1.55; 95% CI, 1.07-2.25), and lowest for estradiol (CEE-estradiol: OR = 1.33; 95% CI, 1.02-1.72). Combined hormonal contraceptives elevated risk 5 times higher than no exposure (OR = 5.22; 95% CI, 4.67-5.84) and 3 times higher than oral MHT (OR = 3.65; 95% CI, 3.09-4.31). Conclusion: The risk of VTE is much lower with MHT than combined hormone contraceptives and varies by hormone formulation and route of exposure. Transdermal MHT did not elevate risk. Oral MHT combinations with estradiol were lower risk than other forms of estrogen. Oral combined hormone contraceptives had much higher risk than oral combined hormonal MHT.

Resident Self-assessment and Clinical Competency Committee Evaluations in Family Medicine: A Single-Institution Study.

BACKGROUND AND OBJECTIVES: We sought to describe the process of integrating resident self-assessments into milestone assessments at the University of Texas Medical Branch Family Medicine Residency Program in Galveston, Texas. We compared resident self-assessments across milestones to Clinical Competency Committee (CCC) assessments across terms (fall versus spring) and by postgraduate year (PGY). METHODS: In fall 2020, the milestone assessment process was updated to include a resident milestone self-assessment, which was used as the starting point for CCC assessment. We calculated mean and standard deviation of average milestone scores for both self-assessment and CCC for each PGY. We used repeated measure analysis of variance to examine within- and between-subject effects. RESULTS: Self-assessment and CCC assessments were completed for 30 postgraduate trainees for spring 2020 and fall 2021 terms, for a total of 60 self- and 60 CCC assessments. CCC score was similar to self-assessment. There were larger variations in the resident self-assessment scores than CCC scores. Self-assessment scores increased by PGY, but were not different between fall and spring terms. We found a significant three-way interaction of assessors, terms, and PGYs. CONCLUSIONS: Resident milestone self-assessment enables residents to participate in the assessment process, and when differences exist between self- and CCC assessments, specific feedback can be given based on individual milestone skills. Our study showed progression between PGY regardless of the assessor, but only CCC assessment showed significant differences between terms.

Changing Missions of Medical Schools and Trends in Medical Student Diversity.

BACKGROUND AND OBJECTIVES: Improving diversity in the physician workforce continues to be a challenge and a priority for medical schools. Establishing a school-wide mission statement that addresses diversity, equity, and inclusion can help support efforts to increase the number of underrepresented in medicine (URM) graduates. METHODS: In this study, we analyzed changes in medical school mission statements between 2013 and 2021 and correlated changes in mission statements with trends in URM student representation. We performed a web search of 136 medical schools' mission statements and categorized them based on whether they changed their mission statement to add diversity or equity language. We then obtained demographic data of enrolled students at each school and identified the percentage of students identifying as URM in each academic year. We used mixed-effects regression and pair fixed effects linear regression to examine trends in URM student representation and the association between URM student representation and whether a school added diversity and equity content to its mission statement. RESULTS: We found that URM student representation increased by 0.4% per year at schools that added diversity and equity content to their mission statements. CONCLUSIONS: Changing medical schools' mission statements to reflect values of diversity, equity, and inclusion was associated with an increase of less than a 1% per year in URM representation. More research is needed to explore relationships between URM representation and medical school mission statements.

Addressing Training Gaps: A Competency-Based, Telehealth Training Initiative for Community Health Workers.

Background: To overcome vast variations in Community Health Worker (CHW) training, investigators for the CHW Core Consensus Project (CCCP) derived three types of CHW (Category 1, 2, 3) and established competencies for each category. However, studies are needed that implement these competencies in real-world settings. Objective: Using the six competency domains of the CCCP as a theoretical backbone, we developed and evaluated a training for Category 1 CHWs, individuals whose focus is on community outreach and advocacy. Methods: We developed five telehealth-based, bilingual (Spanish/English) training sessions and implemented them among Category 1 Latino(a) CHWs. We measured the number of CHWs who achieved ≥70% correct on a domain-based posttest, attendance, and qualitative feedback. Results: All (18/18) CHWs achieved at least 70% on the posttest (mean: 93.7%; range 73.3-100%). Training attendance was 98.9%. Using a six-point scale, CHWs reported high levels of satisfaction overall (5.72 ± 0.57/6.0), with telehealth (5.72 ± 0.58/6.0), effectiveness of teaching strategies/methods (5.89 ± 0.32/6.0), achieving training objectives (5.96 ± 0.15/6.0), knowledge improvement (5.72 ± 0.57/6.0), and interest (5.78 ± 0.43/6.0). Conclusion: We successfully developed and evaluated a bilingual training program for Category 1 CHWs to address core competency gaps. High CHW attendance reinforces the value of telehealth modalities and their potential to increase the reach for CHW training. To overcome gaps in chronic disease training, investigations are needed to address additional CHW trainings. Trial Registration: NCT04835493.

Statin Use and the Risk of Venous Thromboembolism in Women Taking Hormone Therapy.

Importance: Although hormone therapy (HT) in perimenopausal women is associated with increased risk for venous thromboembolism (VTE), it is unclear to what extent statins may mitigate this HT-associated risk. Objective: To estimate VTE risk in women aged 50 to 64 years taking HT with or without statins. Design, Setting, and Participants: This nested case-control study analyzed data from a commercially insured claims database in the US. Eligible participants included women aged 50 to 64 years with at least 1 year of continuous enrollment between 2008 and 2019. Data analysis occurred from January 2022 to August 2023. Exposure: Filled prescriptions for estrogens, progestogens, and statins were recorded in the 12 months prior to index. Recent HT was defined as any estrogen or progestogen exposure within 60 days before the index date. Current statin exposure was defined as 90 or more days of continuous exposure prior to and including the index date. Statin intensity was defined by the statin exposure 30 days prior to index. Main Outcomes and Measures: Cases were identified with VTE diagnoses (diagnostic codes) preceded by at least 12 months without VTE and followed within 30 days by anticoagulation, an inferior vena cava filter placement, or death. Controls were matched to cases (10:1) on date and age. Conditional logistic regression models estimated risk for HT and statin exposures with odds ratios (OR), adjusted for comorbidities. Conditional logistic regression models were used to estimate VTE risk for HT and statin exposures with odds ratios (ORs), adjusted for comorbidities. Intensity of statin therapy was measured as a subgroup analysis. Results: The total sample of 223 949 individuals (mean [SD] age, 57.5 [4.4] years) included 20 359 cases and 203 590 matched controls. Of the entire sample, 19 558 individuals (8.73%) had recent HT exposure and 36 238 individuals (16.18%) had current statin exposure. In adjusted models, individuals with any recent HT exposure had greater odds of VTE compared with those with no recent HT exposure (OR, 1.51; 95% CI, 1.43-1.60). Individuals receiving current statin therapy had lower odds of VTE compared with those with no current statin exposure (OR, 0.88; 95% CI, 0.84-0.93). When compared with those not recently taking HT or statins, the odds of VTE were greater for those taking HT without statins (OR, 1.53; 95% CI, 1.44-1.63) and for those taking HT with statins (OR, 1.25; 95% CI, 1.10-1.43), but were lower for those taking statins without HT (OR, 0.89; 95% CI, 0.85-0.94). Individuals taking HT with statin therapy had 18% lower odds of VTE than those taking HT without statins (OR, 0.82; 95% CI, 0.71-0.94) and there was greater risk reduction with higher intensity statins. Conclusions and Relevance: In this case-control study, statin therapy was associated with reduced risk of VTE in women taking HT, with greater risk reduction with high-intensity statins. These findings suggest that statins may reduce risk of VTE in women exposed to HT and that HT may not be contraindicated in women taking statins.

Determining call-to-entry rate and recruitment barriers in clinical studies for community clinics serving low-income populations: a cohort study.

BACKGROUND: Recruitment for clinical studies is challenging. To overcome barriers, investigators have previously established call-to-entry rates to assist in planning. However, rates specific to low-income minority populations are needed to account for additional barriers to enrolment these individuals face. OBJECTIVE: To obtain a call-to-entry rate in a low-income uninsured Hispanic population with chronic disease. METHODS: We used data from four of our randomised clinical studies to determine the call-to-entry rate for individuals (n=1075) with or at risk for type 2 diabetes: participants needed/potential participants contacted=recruitment rate (yield). Research staff contacted potential participants to enrol in a study that evaluated 6 month diabetes programmes at community clinics from 2015 to 2020. We recorded call-to-entry rates, reasons for declining the study, show rates, and attrition. RESULTS: The call-to-entry rate was 14.5%. Forty per cent of potential participants could not be contacted, and 30.6%, 19.1%, and 5.4% responded yes, no, and maybe, respectively. No show percentages were 54% for yes and 91.4% for maybe responders. The majority (61.6%) declined due to inability to attend; reasons to decline included work (43%), eligibility (18%), transportation (10%), out of town (9%), did not think they needed the programme (7%) and other/unknown (14%). Being a physician predicted inability to reach participants (adjusted OR 2.91, 95% CI 1.73 to 4.90). Attrition was 6.8%. CONCLUSIONS: We described a call-to-entry rate and detailed recruitment data, including reasons to decline the study. This valuable information can assist investigators in study planning and overcoming enrolment barriers in low-income populations. Telehealth-based or strategies that limit transportation needs may increase participant involvement. TRIAL REGISTRATION NUMBER: NCT03394456.

Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial.

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID50 titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037 .

Bivalent and Monovalent SARS-CoV-2 Variant Vaccine Boosters Improve coverage of the known Antigenic Landscape: Results of the COVID-19 Variant Immunologic Landscape (COVAIL) Trial.

Vaccine protection against COVID-19 wanes over time and has been impacted by the emergence of new variants with increasing escape of neutralization. The COVID-19 Variant Immunologic Landscape (COVAIL) randomized clinical trial (clinicaltrials.gov NCT05289037) compares the breadth, magnitude and durability of antibody responses induced by a second COVID-19 vaccine boost with mRNA (Moderna mRNA-1273 and Pfizer-BioNTech BNT162b2), or adjuvanted recombinant protein (Sanofi CoV2 preS DTM-AS03) monovalent or bivalent vaccine candidates targeting ancestral and variant SARS-CoV-2 spike antigens (Beta, Delta and Omicron BA.1). We found that boosting with a variant strain is not associated with loss in neutralization against the ancestral strain. However, while variant vaccines compared to the prototype/wildtype vaccines demonstrated higher neutralizing activity against Omicron BA.1 and BA.4/5 subvariants for up to 3 months after vaccination, neutralizing activity was lower for more recent Omicron subvariants. Our study, incorporating both antigenic distances and serologic landscapes, can provide a framework for objectively guiding decisions for future vaccine updates.

The Social, Behavioral, and Ethical Modalities of COVID-19 on HIV Care in South Africa: A Systematic Review.

The profound public health impact of the novel outbreak of the SARS-CoV-2 virus in 2019 has been unparalleled in the last century. Rapid spread of the disease and a high death toll fueled the development and global rollout of effective vaccines regardless of the massive inequitable access. However, some public health measures intended to control COVID-19 have had collateral effects on the control of other infectious diseases. In this systematic review, we analyze the impact of the COVID-19 pandemic on efforts to control HIV in South Africa, emphasizing the social, ethical, and behavioral ramifications. The SCOPUS, PubMed, Ovid, PsychINFO, and Cochrane Library databases were searched for publications between March 2020 and January 2022. Of the 854 articles identified, 245 were found duplicated, and 609 were screened, 241 of which were potentially eligible, and 15 of which were ultimately included. Although no studies on the ethical implications were eligible for our study criteria due to insufficient primary data to perform an analysis on, we explored this topic in the Discussion section of this paper. We confirm declines in ART, PrEP, and HIV testing during the initial lockdown period, with slight variations across the South African provinces. Protecting routine services and reducing the disease burden on high-risk nations such as South Africa is imperative moving forward with the pandemic.