Model for Evaluating Antimicrobial Therapy To Prevent Life-Threatening Bacterial Infections following Exposure to a Medically Significant Radiation Dose.

More evidence is needed to support recommendations for medical management of acute radiation syndrome (ARS) and associated infections resulting from a radiological/nuclear event. While current guidelines recommend the administration of antibiotics to chemotherapy patients with febrile neutropenia, the clinical benefit is unclear for acute radiation injury patients. A well-characterized nonhuman primate (NHP) model of hematopoietic ARS was developed that incorporates supportive care postirradiation. This model evaluated the efficacy of myeloid growth factors within 24 to 48 h after total body irradiation (TBI). However, in this model, NHPs continued to develop life-threatening bacterial infections, even when granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor was administered in combination with antibiotic monotherapy. In this study, we evaluated the efficacy of combination antibiotic therapies administered to NHPs following 7.4-Gy TBI to understand the occurrence of bacterial infection in NHPs with hematopoietic ARS. We compared enrofloxacin-linezolid, enrofloxacin-cefepime, and enrofloxacin-ertapenem to enrofloxacin monotherapy. The primary endpoint was 60-day postirradiation mortality, with secondary endpoints of overall survival time, incidence of bacterial infection, and bacteriologic culture with antimicrobial susceptibility testing. We observed that enrofloxacin-ertapenem significantly increased survival compared to enrofloxacin monotherapy. Bacteria isolated from nonsurviving macaques with systemic bacterial infections exhibited uniform resistance to enrofloxacin and variable resistance to beta-lactam antibiotics, linezolid, gentamicin, and azithromycin. Multidrug antibiotic resistance was observed in Enterococcus spp. and Escherichia coli. We conclude that antibiotic combination therapies appear to be more effective than monotherapy alone but acknowledge that more work is needed to identify an optimal antimicrobial therapy.

Applied global health diplomacy: profile of health diplomats accredited to the UNITED STATES and foreign governments.

BACKGROUND: Global health diplomacy (GHD) is a burgeoning field bridging the priorities of global health and foreign affairs. Given the increasing need to mobilize disparate global health stakeholders coupled with the need to design complex public health partnerships to tackle issues of international concern, effective and timely cooperation among state actors is critical. Health Attachés represent this coordination focal point and are key diplomatic professionals at the forefront of GHD. Despite their unique mandate, little is published about this profession and the perspectives of those who work in the field. METHODS: Through purposive sampling, we performed in-depth qualitative interviews with seven Health Attachés: three foreign Health Attachés accredited to the United States and four U.S. Health Attachés accredited to foreign governments. Our interviews explored four key topics: the role and mission of Health Attachés, skills needed to perform GHD, examples of successes and challenges in accomplishing their respective missions, and suggestions for the future development of the diplomatic profession. RESULTS: We identified several lessons to apply to the growing field of GHD. First, GHD actors need to receive appropriate training to successfully negotiate the intersection of global health and foreign affairs. Participants suggested several areas of training that would benefit GHD actors: diplomacy and negotiation, applied science, and cross-cultural competency. Second, participants articulated the need for a career path for GHD practitioners, increased opportunities for on-the-job training and mentored experiences, and GHD competencies with defined levels of mastery that can be used in occupational evaluation and career development. CONCLUSIONS: Our findings indicate that skills in diplomacy and negotiation, applied science, and cross cultural competency are essential for the statecraft of Health Attachés. Additionally, establishing a clear career pathway for Health Attachés is critical for future maturation of the profession and for fostering effective global health action that aligns public health and foreign diplomacy outcomes. Achieving these goals would ensure that this special cadre of diplomats could effectively practice GHD and would also better position Health Attachés to take the lead in advancing shared global health goals among nation states in a new era of twenty-first century diplomacy.

Maternal Influences on Access to and Use of Infant ARVs and HIV Health Services in Uganda.

Vertical transmission of HIV is responsible for about 14 % of new HIV cases reported each year in sub-Saharan Africa. Barriers that prevent women from accessing and using antiretroviral medications (ARVs) for themselves and their infants perpetuate the epidemic. To identify influences on access to and use of infant HIV health services, specifically nevirapine administration, we conducted a mixed methods study among HIV-positive women in Uganda. This included a cross-sectional survey (n = 384) and focus group discussions (n = 6, 5-9 participants each). Of the 384 women, 80 % gave nevirapine to their infants within 72 h of birth. Factors independently associated with nevirapine administration were lack of maternal adherence to ARVs (AOR 3.55, 95 % CI 1.36-9.26) and attending a support group (AOR 2.50, 95 % CI 1.06-5.83). Non-health facility births were inversely related to nevirapine use (AOR 0.02, 95 % CI 0.003-0.09). Focus group discussions identified four themes impacting access and use: attending a support group, health care worker attitudes, lack of partner support, and poor health messaging regarding ARVs. Improving health care worker messaging regarding ARVs and providing women with needed support to access and use infant ARV prophylaxis is critical to overcoming access barriers. Eliminating these barriers may prevent numerous HIV infections each year saving the lives of many HIV-exposed infants.

Outcomes and Cost-Effectiveness of Integrating HIV and Nutrition Service Delivery: Pilots in Malawi and Mozambique.

This paper provides the first estimates of impact and cost-effectiveness for integrated HIV and nutrition service delivery in sub-Saharan Africa. HIV and undernutrition are synergistic co-epidemics impacting millions of children throughout the region. To alleviate this co-epidemic, UNICEF supported small-scale pilot programs in Malawi and Mozambique that integrated HIV and nutrition service delivery. We use trends from integration sites and comparison sites to estimate the number of lives saved, infections averted and/or undernutrition cases cured due to programmatic activities, and to estimate cost-effectiveness. Results suggest that Malawi's program had a cost-effectiveness of $11-29/DALY, while Mozambique's was $16-59/DALY. Some components were more effective than others ($1-4/DALY for Malawi's Male motivators vs. $179/DALY for Mozambique's One stop shops). These results suggest that integrating HIV and nutrition programming leads to a positive impact on health outcomes and should motivate additional work to evaluate impact and determine cost-effectiveness using an appropriate research design.

The cost of accessing infant HIV medications and health services in Uganda.

Patient costs are a critical barrier to the elimination of mother to child HIV transmission. Despite the Ugandan government providing free public HIV services, infant antiretroviral (ARV) prophylaxis coverage remains low (25%). To understand costs mothers incur in accessing ARV prophylaxis for their infants, we conducted a mixed methods study to quantify and identify their direct costs. We used cross-sectional survey data and focus group discussions from 49 HIV-positive mothers in Uganda. Means and standard deviations were calculated for the direct costs (e.g., transportation, caretaker, services/medications) involved in accessing infant HIV services. The direct cost of attending HIV clinic visits averaged $3.71 (SD = $3.52). Focus group discussions identified two costs hindering access to infant HIV services: transportation costs and informal service charges. All participants reported significant costs associated with accessing infant HIV services - the equivalent of 2-3 days' income. To address transportation costs, community and home care models should be explored. Additionally, stricter policies and oversight should be implemented to prevent informal HIV service charges.

Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures: Overlapping science in radiation and sulfur mustard injuries to lung and skin.

PURPOSE: To summarize presentations and discussions from the 2022 trans-agency workshop titled "Overlapping science in radiation and sulfur mustard (SM) exposures of skin and lung: Consideration of models, mechanisms, organ systems, and medical countermeasures." METHODS: Summary on topics includes: (1) an overview of the radiation and chemical countermeasure development programs and missions; (2) regulatory and industry perspectives for drugs and devices; 3) pathophysiology of skin and lung following radiation or SM exposure; 4) mechanisms of action/targets, biomarkers of injury; and 5) animal models that simulate anticipated clinical responses. RESULTS: There are striking similarities between injuries caused by radiation and SM exposures. Primary outcomes from both types of exposure include acute injuries, while late complications comprise chronic inflammation, oxidative stress, and vascular dysfunction, which can culminate in fibrosis in both skin and lung organ systems. This workshop brought together academic and industrial researchers, medical practitioners, US Government program officials, and regulators to discuss lung-, and skin- specific animal models and biomarkers, novel pathways of injury and recovery, and paths to licensure for products to address radiation or SM injuries. CONCLUSIONS: Regular communications between the radiological and chemical injury research communities can enhance the state-of-the-science, provide a unique perspective on novel therapeutic strategies, and improve overall US Government emergency preparedness.

Partnering on vaccines to counter multi-drug resistant threats: Workshop proceedings, Biomedical Advanced Research and Development Authority.

On March 12, 2021, the Biomedical Advanced Research and Development Authority (BARDA) sponsored a virtual market research workshop, "Partnering on Vaccines to Counter Multi-Drug Resistant Threats," to discuss the threat of antimicrobial resistance in the context of BARDA's mission space and the challenges encountered during the development of vaccines for specific antimicrobial resistant bacteria. The workshop convened representatives with expertise in vaccine development from government, academia, and industry. This report summarizes the presentations and subsequent discussions from the workshop and highlights existing challenges to advance the development of vaccine candidates for antimicrobial resistant pathogens, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus.

Applying Lessons Learned From COVID-19 Therapeutic Trials to Improve Future ALI/ARDS Trials.

Host-directed therapeutics targeting immune dysregulation are considered the most promising approach to address the unmet clinical need for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) related to coronavirus disease 2019 (COVID-19). To better understand the current clinical study landscape and gaps in treating hospitalized patients with severe or critical COVID-19, we identified COVID-19 trials developing host-directed therapies registered at ClinicalTrials.gov and discussed the factors contributing to the success vs failure of these studies. We have learned, instead of the one-size-fits-all approach, future clinical trials evaluating a targeted immunomodulatory agent in heterogeneous patients with ALI/ARDS due to COVID-19 or other infectious diseases can use immune-based biomarkers in addition to clinical and demographic characteristics to improve patient stratification and inform clinical decision-making. Identifying distinct patient subgroups based on immune profiles across the disease trajectory, regardless of the causative pathogen, may accelerate evaluating host-directed therapeutics in trials of ALI/ARDS and related conditions (eg, sepsis).

How does intimate partner violence affect condom and oral contraceptive Use in the United States?: A systematic review of the literature.

INTRODUCTION: Intimate partner violence (IPV) is estimated to affect 25% of adult women in the United States alone. IPV directly impacts women's ability to use contraception, resulting in many of unintended pregnancies and STIs. This review examines the relationship between IPV and condom and oral contraceptive use within the United States at two levels: the female victim's perspective on barriers to condom and oral contraceptive use, in conjunction with experiencing IPV (Aim 1) and the male perpetrator's perspective regarding condom and oral contraceptive use (Aim 2). STUDY DESIGN: We systematically reviewed and synthesized all publications meeting the study criteria published since 1997. We aimed to categorize the results by emerging themes related to each study aim. RESULTS: We identified 42 studies that met our inclusion criteria. We found 37 studies that addressed Aim 1. Within this we identified three themes: violence resulting in reduced condom or oral contraceptive use (n=15); condom or oral contraceptive use negotiation (n=15); which we further categorized as IPV due to condom or oral contraceptive request, perceived violence (or fear) of IPV resulting in decreased condom or oral contraceptive use, and sexual relationship power imbalances decreasing the ability to use condoms or oral contraceptives; and reproductive coercion (n=7). We found 5 studies that addressed Aim 2. Most studies were cross-sectional, limiting the ability to determine causality between IPV and condom or oral contraceptive use; however, most studies did find a positive relationship between IPV and decreased condom or oral contraceptive use. CONCLUSIONS: Quantitative, qualitative, and mixed methods research has demonstrated the linkages between female IPV victimization/male IPV perpetration and condom or oral contraceptive use. However, additional qualitative and longitudinal research is needed to improve the understanding of dynamics in relationships with IPV and determine causality between IPV, intermediate variables (e.g., contraceptive use negotiation, sexual relationship power dynamics, reproductive coercion), and condom and oral contraceptive use. Assessing the relationship between IPV and reproductive coercion may elucidate barriers to contraceptive use as well as opportunities for interventions to increase contraceptive use (such as forms of contraception with less partner influence) and reduce IPV and reproductive coercion.

Women's perspectives on female-initiated barrier methods for the prevention of HIV in the context of methamphetamine use and partner violence.

BACKGROUND: Female-initiated barrier methods for the prevention of HIV may be an effective alternative for drug-using women who are unable to negotiate safe sex, often as a result of physical and/or sexual partner violence. METHODS: Utilizing a SAVA (substance abuse, violence, and AIDS) syndemic framework, we qualitatively examined perspectives on female condoms and vaginal microbicides among 18 women with histories of methamphetamine abuse and partner violence in San Diego, California. FINDINGS: Most women were not interested in female condoms owing to perceived discomfort, difficulty of insertion, time-intensive effort, and unappealing appearance. Alternatively, most women viewed vaginal microbicides as a useful method. Positive aspects included convenience, ability to disguise as a lubricant, and a sense of control and empowerment. Concerns included possible side effects, timing of application, and unfavorable characteristics of the gel. Acceptability of female-initiated barrier methods was context dependent (i.e., partner type, level of drug use and violence that characterized the sexual relationship). CONCLUSIONS: Findings indicate that efforts are needed to address barriers identified for vaginal microbicides to increase its uptake in future HIV prevention trials and marketing of future Food and Drug Administration-approved products. Strategies should address gender-based inequalities (e.g., partner violence) experienced by drug-using women and promote female empowerment. Education on female-initiated barrier methods is also needed for women who use drugs, as well as health care providers and other professionals providing sexual health care and contraception to women with histories of drug use and partner violence.