Trends in SARS-CoV-2 seroprevalence among pregnant women attending first antenatal care visits in Zambia: A repeated cross-sectional survey, 2021-2022.

SARS-CoV-2 serosurveys help estimate the extent of transmission and guide the allocation of COVID-19 vaccines. We measured SARS-CoV-2 seroprevalence among women attending ANC clinics to assess exposure trends over time in Zambia. We conducted repeated cross-sectional SARS-CoV-2 seroprevalence surveys among pregnant women aged 15-49 years attending their first ANC visits in four districts of Zambia (two urban and two rural) during September 2021-September 2022. Serologic testing was done using a multiplex bead assay which detects IgG antibodies to the nucleocapsid protein and the spike protein receptor-binding domain (RBD). We calculated monthly SARS-CoV-2 seroprevalence by district. We also categorized seropositive results as infection alone, infection and vaccination, or vaccination alone based on anti-RBD and anti-nucleocapsid test results and self-reported COVID-19 vaccination status (vaccinated was having received ≥1 dose). Among 8,304 participants, 5,296 (63.8%) were cumulatively seropositive for SARS-CoV-2 antibodies from September 2021 through September 2022. SARS-CoV-2 seroprevalence primarily increased from September 2021 to September 2022 in three districts (Lusaka: 61.8-100.0%, Chongwe: 39.6-94.7%, Chipata: 56.5-95.0%), but in Chadiza, seroprevalence increased from 27.8% in September 2021 to 77.2% in April 2022 before gradually dropping to 56.6% in July 2022. Among 5,906 participants with a valid COVID-19 vaccination status, infection alone accounted for antibody responses in 77.7% (4,590) of participants. Most women attending ANC had evidence of prior SARS-CoV-2 infection and most SARS-CoV-2 seropositivity was infection-induced. Capturing COVID-19 vaccination status and using a multiplex bead assay with anti-nucleocapsid and anti-RBD targets facilitated distinguishing infection-induced versus vaccine-induced antibody responses during a period of increasing COVID-19 vaccine coverage in Zambia. Declining seroprevalence in Chadiza may indicate waning antibodies and a need for booster vaccines. ANC clinics have a potential role in ongoing SARS-CoV-2 serosurveillance and can continue to provide insights into SARS-CoV-2 antibody dynamics to inform near real-time public health responses.

Complex periprosthetic wound coverage in patients undergoing revision total knee arthroplasty: a single plastic surgeon study.

INTRODUCTION: Options for soft tissue coverage in revision total knee arthroplasty (rTKA) range from primary wound closure to complex muscle flap reconstructions. The purpose of this study was to investigate the institutional experience of wound coverage options for complex soft tissue defects in rTKA. MATERIALS AND METHODS: 77 patients undergoing rTKA with complex wound closure by a single plastic surgeon were retrospectively reviewed. The average follow-up was 30.1 months. In 18 (23.4%) patients, an intraoperative decision for primary closure was made. Fifty-nine patients (76.6%) received either a local fasciocutaneous (N = 18), a medial gastrocnemius (N = 37), a free latissimus dorsi (N = 3) or a lateral gastrocnemius flap (N = 1). Revision-free survival and complication rates were assessed and risk factors were analyzed with Cox-regression analysis. RESULTS: Medial gastrocnemius flaps had significant lower cumulative revision-free survival rates than local fasciocutaneous flaps (P = 0.021) and primary closures (P < 0.001) (42.5% vs. 71.5% vs. 100%,respectively). Comparing the most common complex closure procedures medial gastrocnemius flaps had the highest rate of prolonged wound healing (29.7%) and infection/reinfection (40.5%). Infection-associated flap procedures had significant lower cumulative revision-free survival rates (30.5%) than non-infection associated flap procedures (62.8%,P = 0.047). A history of more than two prior surgeries (HR = 6.11,P < 0.001) and an age ≥ 65 years (HR = 0.30,P = 0.018) significantly increased the risk of revision. CONCLUSIONS: The results of this study indicate that primary closure -if possible- should be preferred to early proactive muscle flap coverage. Even in the hands of an experienced plastic surgeon muscle flaps have high revision and complication rates. The study highlights the need to clarify flap indications and to investigate alternative approaches.

Comparison of HIV prevalence, incidence, and viral load suppression in Zambia population-based HIV impact assessments from 2016 and 2021.

BACKGROUND: The Zambian government has implemented a public health response to control the HIV epidemic in the country. Zambia conducted a population-based HIV impact assessment (ZAMPHIA) survey in 2021 to assess the status of the HIV epidemic to guide its public health programs. METHODS: ZAMPHIA 2021 was a cross-sectional two-stage cluster sample household survey among persons aged ≥15 years conducted in Zambia across all 10 provinces. Consenting participants were administered a standardized questionnaire and whole blood was tested for HIV according to national guidelines. HIV-1 viral load (VL), recent HIV infection, and antiretroviral medications were tested for in HIV-seropositive samples. Viral load suppression (VLS) was defined as <1000 copies/ml. ZAMPHIA 2021 results were compared to ZAMPHIA 2016 for persons aged 15-59 years (i.e., the overlapping age ranges). All estimates were weighted to account for nonresponse and survey design. RESULTS: During ZAMPHIA 2021, of 25 483 eligible persons aged ≥15 years, 18 804 (73.8%) were interviewed and tested for HIV. HIV prevalence was 11.0% and VLS prevalence was 86.2% overall, but was <80% among people living with HIV aged 15-24 years and in certain provinces. Among persons aged 15-59 years, from 2016 to 2021, HIV incidence declined from 0.6% to 0.3% ( P -value: 0.07) and VLS prevalence increased from 59.2% to 85.7% ( P -value: <0.01). DISCUSSION: Zambia has made substantial progress toward controlling the HIV epidemic from 2016 to 2021. Continued implementation of a test-and-treat strategy, with attention to groups with lower VLS in the ZAMPHIA 2021, could support reductions in HIV incidence and improve overall VLS in Zambia.

Test negative case-control study of COVID-19 vaccine effectiveness for symptomatic SARS-CoV-2 infection among healthcare workers: Zambia, 2021-2022.

OBJECTIVES: The study aim was to evaluate vaccine effectiveness (VE) of COVID-19 vaccines in preventing symptomatic COVID-19 among healthcare workers (HCWs) in Zambia. We sought to answer the question, 'What is the vaccine effectiveness of a complete schedule of the SARS-CoV-2 vaccine in preventing symptomatic COVID-19 among HCWs in Zambia?' DESIGN/SETTING: We conducted a test-negative case-control study among HCWs across different levels of health facilities in Zambia offering point of care testing for COVID-19 from May 2021 to March 2022. PARTICIPANTS: 1767 participants entered the study and completed it. Cases were HCWs with laboratory-confirmed SARS-CoV-2 and controls were HCWs who tested SARS-CoV-2 negative. Consented HCWs with documented history of vaccination for COVID-19 (vaccinated HCWs only) were included in the study. HCWs with unknown test results and unknown vaccination status, were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was VE among symptomatic HCWs. Secondary outcomes were VE by: SARS-CoV-2 variant strains based on the predominant variant circulating in Zambia (Delta during May 2021 to November 2021 and Omicron during December 2021 to March 2022), duration since vaccination and vaccine product. RESULTS: We recruited 1145 symptomatic HCWs. The median age was 30 years (IQR: 26-38) and 789 (68.9%) were women. Two hundred and eighty-two (24.6%) were fully vaccinated. The median time to full vaccination was 102 days (IQR: 56-144). VE against symptomatic SARS-CoV-2 infection was 72.7% (95% CI: 61.9% to 80.7%) for fully vaccinated participants. VE was 79.4% (95% CI: 58.2% to 90.7%) during the Delta period and 37.5% (95% CI: -7.0% to 63.3%) during the Omicron period. CONCLUSIONS: COVID-19 vaccines were effective in reducing symptomatic SARS-CoV-2 among Zambian HCWs when the Delta variant was circulating but not when Omicron was circulating. This could be related to immune evasive characteristics and/or waning immunity. These findings support accelerating COVID-19 booster dosing with bivalent vaccines as part of the vaccination programme to reduce COVID-19 in Zambia.

Gluteus maximus transfer for wound closure and treatment of abductor deficiency: a single-plastic surgeon series.

INTRODUCTION: Due to the increasing number of total hip arthroplasties (THA), the number and complexity of revision procedures are also on the rise. For complex cases such as periprosthetic joint infections with soft tissue compromise or for abductor muscle deficiencies, one of the treatment options is a gluteus maximus flap (GMF) that covers dead space and can help restore the failed abductor mechanism. The purpose of this study is to investigate the outcomes of a single-plastic surgeon's series of GMF procedures. MATERIALS AND METHODS: This retrospective review reports on 57 patients (mean follow-up 39.2 months) undergoing GMF transfers for abductor insufficiency on native hip (N = 16), for abductor insufficiency in aseptic revision THA (rTHA) (N = 16), for soft tissue defects in aseptic rTHA (N = 8) and for soft tissue defects in septic rTHA (N = 17) by a single plastic surgeon over a 10-year period. Revision-free survival and complication rates were assessed and risk factors were analyzed with Cox-regression analysis. RESULTS: The reoperation-free survival rate of GMF for abductor insufficiency in native hips was 100%. GMF procedures for soft tissue defects in septic rTHA had the lowest cumulative revision-free survival (34.3%) and highest reinfection rates (53.9%). More than three prior surgeries (HR = 2.9, p = 0.020), presence of infection (HR = 3.2, p = 0.010) and resistant organisms (HR = 3.1, p = 0.022) significantly increased the risk of revision. CONCLUSIONS: GMF is a viable option for addressing abductor insufficiency in native hip joints. However, high revision and complication rates are reported for GMF in septic rTHA. This study highlights the need to clarify the circumstances for which the flap reconstruction will be indicated.

Hypertension among persons living with HIV-Zambia, 2021; A cross-sectional study of a national electronic health record system.

Hypertension is a major risk factor for cardiovascular disease, which is a common cause of death in Zambia. Data on hypertension prevalence in Zambia are scarce and limited to specific geographic areas and/or populations. We measured hypertension prevalence among persons living with HIV (PLHIV) in Zambia using a national electronic health record (EHR) system. We did a cross-sectional study of hypertension prevalence among PLHIV aged ≥18 years during 2021. Data were extracted from the SmartCare EHR, which covers ~90% of PLHIV on treatment in Zambia. PLHIV with ≥2 clinical visits in 2021 were included. Hypertension was defined as ≥2 elevated blood pressure readings (systolic ≥140 mmHg/diastolic ≥90 mmHg) during 2021 and/or on anti-hypertensive medication recorded in their EHR ≤5 years. Logistic regression was used to assess for associations between hypertension and demographic characteristics. Among 750,098 PLHIV aged ≥18 years with ≥2 visits during 2021, 101,363 (13.5%) had ≥2 recorded blood pressure readings. Among these PLHIV, 14.7% (95% confidence interval [CI]: 14.5-14.9) had hypertension. Only 8.9% of PLHIV with hypertension had an anti-hypertensive medication recorded in their EHR. The odds of hypertension were greater in older age groups compared to PLHIV aged 18-29 years (adjusted odds ratio [aOR] for 30-44 years: 2.6 [95% CI: 2.4-2.9]; aOR for 45-49 years: 6.4 [95% CI: 5.8-7.0]; aOR for ≥60 years: 14.5 [95% CI: 13.1-16.1]), urban areas (aOR: 1.9 [95% CI: 1.8-2.1]), and on ART for ≥6-month at a time (aOR: 1.1 [95% CI: 1.0-1.2]). Hypertension was common among PLHIV in Zambia, with few having documentation of treatment. Most PLHIV were excluded from the analysis because of missing BP measurements. Strengthening integrated management of non-communicable diseases in HIV clinics might help to diagnose and treat hypertension in Zambia. Addressing missing data of routine clinical data (like blood pressure) could improve non-communicable diseases surveillance in Zambia.

Hepatitis B viral replication markers and hepatic fibrosis in untreated chronic hepatitis B virus infection with and without HIV coinfection in Zambia.

BACKGROUND: To inform novel therapies, a more nuanced understanding of HIV's impact on hepatitis B virus (HBV) natural history is needed, particularly in high burden countries. METHODS: In Lusaka, Zambia, we compared prospectively recruited adults (18+ years) with chronic HBV infection, with and without HIV. We excluded those with prior antiviral treatment experience or HBV diagnosis due to clinical suspicion (rather than routine testing). We assessed HBV DNA levels, hepatitis B e antigen (HBeAg), CD4 + (if HIV coinfection), and liver disease (transient elastography, serum alanine aminotransferase). In multivariable analyses, we evaluated the association of HIV overall and by level of CD4 + count on these markers. RESULTS: Among 713 adults analyzed, median age was 33 years, 63% were male, and 433 had HBV/HIV coinfection. Median CD4 + count was 200 cells/µl. HBV DNA was greater than 2000 IU/ml for 311 (51.0%) and 227 (32.5%) were HBeAg-positive. 15.5% had advanced fibrosis or cirrhosis. HIV coinfection was associated with five-fold increased HBV DNA levels [adjusted geometric mean ratio, 5.78; 95% confidence interval (CI), 2.29-14.62] and two times the odds of HBeAg-positivity (adjusted odds ratio, 2.54; 95% CI, 1.59-4.08). These associations were significant only at CD4 + counts 100-350 and <100 cells/µl. HIV was not associated with markers of fibrosis or ALT. DISCUSSION: HIV's impact on HBV natural history likely depends on the degree and duration of immune suppression. There is strong rationale to monitor HBV DNA in people with HBV/HIV coinfection and immune suppression. A better understanding is needed of mechanisms of increased liver-related mortality in people with HBV/HIV coinfection.

Using mortuary and burial data to place COVID-19 in Lusaka, Zambia within a global context.

Reported COVID-19 cases and associated mortality remain low in many sub-Saharan countries relative to global averages, but true impact is difficult to estimate given limitations around surveillance and mortality registration. In Lusaka, Zambia, burial registration and SARS-CoV-2 prevalence data during 2020 allow estimation of excess mortality and transmission. Relative to pre-pandemic patterns, we estimate age-dependent mortality increases, totalling 3212 excess deaths (95% CrI: 2104-4591), representing an 18.5% (95% CrI: 13.0-25.2%) increase relative to pre-pandemic levels. Using a dynamical model-based inferential framework, we find that these mortality patterns and SARS-CoV-2 prevalence data are in agreement with established COVID-19 severity estimates. Our results support hypotheses that COVID-19 impact in Lusaka during 2020 was consistent with COVID-19 epidemics elsewhere, without requiring exceptional explanations for low reported figures. For more equitable decision-making during future pandemics, barriers to ascertaining attributable mortality in low-income settings must be addressed and factored into discourse around reported impact differences.

Synergistic Strategies to Accelerate the Development of Function-Promoting Therapies: Lessons From Operation Warp Speed and Oncology Drug Development.

BACKGROUND: Functional limitations and physical disabilities associated with aging and chronic disease are major concerns for human societies and expeditious development of function-promoting therapies is a public health priority. METHODS: Expert panel discussion. RESULTS: The remarkable success of Operation Warp Speed for the rapid development of COVID-19 vaccines, COVID-19 therapeutics, and of oncology drug development programs over the past decade have taught us that complex public health problems such as the development of function-promoting therapies will require collaboration among many stakeholders, including academic investigators, the National Institutes of Health, professional societies, patients and patient advocacy organizations, the pharmaceutical and biotechnology industry, and the U.S. Food and Drug Administration. CONCLUSIONS: There was agreement that the success of well designed, adequately powered clinical trials will require careful definitions of indication/s, study population, and patient-important endpoints that can be reliably measured using validated instruments, commensurate resource allocation, and versatile organizational structures such as those used in Operation Warp Speed.

Effects of the ECHO tele-mentoring program on HIV/TB service delivery in health facilities in Zambia: a mixed-methods, retrospective program evaluation.

BACKGROUND: In the quest to ensure that quality healthcare is provided to all citizens through building healthcare worker capacity and extending reach for expert services, Zambia's Ministry of Health (MoH) in collaboration with its partners PEPFAR through the CDC and HRSA, began to implement the Extension for Community Healthcare Outcomes (ECHO) tele-mentoring program across the country through the Health Workers for the 21st Century (HW21) Project and University Teaching Hospital HIV/AIDS Project (UTH-HAP). This ECHO tele-mentoring approach was deemed pivotal in helping to improve the human immunodeficiency virus (HIV) service delivery capacity of health care workers. METHOD: The study used a mixed method, retrospective program evaluation to examine ECHO participants' performance in the management of HIV/AIDS patients in all the 10 provinces of Zambia. CASE PRESENTATION: A phenomenological design was applied in order to elicit common experiences of ECHO users through focus group discussions using semi-structured facilitation guides in four provinces (Eastern, Lusaka, Southern and Western) implementing ECHO tele-mentoring approach. These provinces were purposively selected for this study. From which, only participants that had a monthly frequency of ECHO attendance of ten (10) and above were selected. The participants were purposively selected based on the type of cadre as well as facility type so that the final sample consisted of Doctors, Nurses, Midwives, Clinical Officers, Medical Licentiates, Pharmacy and Laboratory Personnel. All sessions were audio recorded and transcribed by the data collectors. A thematic content analysis approach was adopted for analyzing content of the interview's transcripts. RESULTS: Enhanced knowledge and skills of participants on HIV/TB improved by 46/70 (65.7%) in all provinces, while 47/70 (67.1%) of the participants reported that ECHO improved their clinical practice. Further, 12/70 (17.1%) of participants in all provinces reported that presenter/presentation characteristics facilitated ECHO implementation and participation. While, 15/70(21.4%) of the participants reported that ownership of the program had contributed to ECHO implementation and participation. Coordination, another enabler accounted for 14/70 (20%). Inclusiveness was reported as a barrier by 16/70 (22.8%) of the participants while 6/70 (8.6%) of them reported attitudes as a barrier (8.6%) to ECHO participation. In addition, 34/70 (48.6%) reported poor connectivity as a barrier to ECHO implementation and participation while 8/70 (11.5%) of the participants reported that the lack of ownership of the ECHO program was a barrier. 22/70 (31.4%) reported that increased workload was also a barrier to the program's implementation. CONCLUSION: Consistent with its logical pathway model, healthcare providers' participation in ECHO sessions and onsite mentorship contributed to improved knowledge on HIV/TB among health care providers and patient health outcomes. In addition, barriers to ECHO implementation were intrinsic to the program its self, such as coordination, presenter and presentation characteristics other barriers were extrinsic to the program such as poor connectivity, poor infrastructure in health facilities and negative attitudes towards ECHO. Improving on intrinsic factors and mitigating extrinsic factors may help improve ECHO outcomes and scale-up plans.

Intersection of alcohol use, HIV infection, and the HIV care continuum in Zambia: nationally representative survey.

Through a nationally-representative household survey, we measured the prevalence and correlates of unhealthy alcohol use (UAU) in Zambia and its association with the HIV care continuum. Adolescent and adult (ages 15-59 years) data, including the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), from the 2016 Zambia Population-based HIV Impact Assessment, were analyzed. UAU was defined as AUDIT-C of 3 + points for women and 4 + for men. Among 20,923 participants, 15.3% had UAU; this was 21.6% among people living with HIV (PLWH). Male sex, increasing age, being employed, urban residence, and having HIV were independent correlates of UAU (all P < 0.05). Among PLWH, UAU was associated with reduced HIV diagnosis (adjusted odds ratio [AOR]: 0.66, 95% CI 0.50-0.88) and non-significant trends toward reduced ART use if diagnosed (AOR: 0.73, 95% CI 0.73-1.10) and reduced viral suppression (VS) if on ART (AOR: 0.91, 95% CI 0.57-1.44). Overall, UAU was linked to 25% lower odds of VS compared to abstinence. UAU in Zambia disproportionately affects certain groups including PLWH. Achieving and sustaining HIV epidemic control in Zambia will require evidence-based approaches to screen and treat UAU.

A Study to Evaluate Relative Bioavailability, Food Effect, and Pharmacodynamics of Tropifexor, a Farnesoid X Receptor Agonist, in Healthy Participants.

This open-label, randomized, 3-treatment, 3-period, 6-sequence, crossover study in healthy subjects compared the pharmacokinetic and pharmacodynamic properties of a lipid-based (soft gelatin capsule) prototype final market image (pFMI) formulation of tropifexor (90-µg) to its clinical service form (CSF) and assessed the food effect for the pFMI formulation. In the fasted state, drug exposure was higher for the pFMI. The geometric mean ratios for pFMI versus CSF of peak concentration and area under the concentration-time curve were 2.0 and 1.5, respectively. No food effect was apparent for the pFMI formulation, and the geometric mean ratios for pFMI fed versus pFMI fasted of peak concentration and area under concentration-time curve were 1.0 and 1.0 respectively. Despite having lower systemic exposure, the CSF formulation provided a higher pharmacological response for the gut biomarker fibroblast growth factor 19. Under fasted conditions, fibroblast growth factor 19 maximum change from baseline serum concentration after drug administration and area under the change from baseline serum concentration-time curve from time 0 to 24 hours were 36% for CSF and 12% for FMI. For a second biomarker, serum 7-alpha hydroxy-4-cholest-3-one, the pharmacological activity was comparable between CSF (fasted) and pFMI (both fasted and fed states). The pFMI offers advantages over the CSF in terms of insensitivity to food effect, lower intersubject variability, and overcoming solubility limitations.

Ophthalmic Manifestations of ROSAH (Retinal Dystrophy, Optic Nerve Edema, Splenomegaly, Anhidrosis, and Headache) Syndrome, an Inherited NF κB-Mediated Autoinflammatory Disease with Retinal Dystrophy.

PURPOSE: We aimed to characterize the ocular phenotype of patients with ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome and their response to therapy. DESIGN: Single-center observational case study. PARTICIPANTS: Eleven patients with a diagnosis of ROSAH syndrome and mutation in ALPK1 were included. METHODS: Patients with molecularly confirmed ROSAH syndrome underwent ophthalmic evaluation, including visual acuity testing, slit-lamp and dilated examinations, color fundus and autofluorescence imaging, fluorescein angiography, OCT, and electrophysiologic testing. MAIN OUTCOME MEASURES: Visual acuity, electrophysiology, fluorescein angiography, and OCT findings. RESULTS: Eleven individuals (6 female and 5 male patients) from 7 families ranging in age from 7.3 to 60.2 years at the time of the initial evaluation were included in this study. Seven patients were followed up for a mean of 2.6 years (range, 0.33-5.0 years). Best-corrected visual acuity at baseline ranged from 20/16 to no light perception. Variable signs or sequelae of intraocular inflammation were observed in 9 patients, including keratic precipitates, band keratopathy, trace to 2+ anterior chamber cells, cystoid macular edema, and retinal vasculitis on fluorescein angiography. Ten patients were observed to show optic disc elevation and demonstrated peripapillary thickening on OCT. Seven patients showed retinal degeneration consistent with a cone-rod dystrophy, with atrophy tending to involve the posterior pole and extending peripherally. One patient with normal electroretinography findings and visual evoked potential was found to have decreased Arden ratio on electro-oculography. CONCLUSIONS: Leveraging insights from the largest single-center ROSAH cohort described to date, this study identified 3 main factors as contributing to changes in visual function of patients with ROSAH syndrome: optic nerve involvement; intraocular inflammation, including cystoid macular edema; and retinal degeneration. More work is needed to determine how to arrest the progressive vision loss associated with ROSAH syndrome. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Clinical Characteristics and Outcomes of Patients Hospitalized With COVID-19 During the First 4 Waves in Zambia.

Importance: Few epidemiologic studies related to COVID-19 have emerged from countries in Africa, where demographic characteristics, epidemiology, and health system capacity differ from other parts of the world. Objectives: To describe the characteristics and outcomes of patients admitted to COVID-19 treatment centers, assess risk factors for in-hospital death, and explore how treatment center admissions were affected by COVID-19 waves in Zambia. Design, Setting, and Participants: This retrospective cohort study assessed patients admitted to COVID-19 treatment centers in 5 Zambian cities between March 1, 2020, and February 28, 2022. Exposures: Risk factors for in-hospital mortality, including patient age and severity of COVID-19, at treatment center admission. Main Outcomes and Measures: Patient information was collected, including inpatient disposition (discharged or died). Differences across and within COVID-19 waves were assessed. Mixed-effects logistic regression models were used to assess associations between risk factors and in-hospital mortality as well as between characteristics of admitted patients and timing of admission. Results: A total of 3876 patients were admitted during 4 COVID-19 waves (mean [SD] age, 50.6 [19.5] years; 2103 male [54.3%]). Compared with the first 3 waves (pooled), the proportion of patients who were 60 years or older admitted during wave 4, when the Omicron variant was circulating, was significantly lower (250 of 1009 [24.8%] vs 1116 of 2837 [39.3%]; P < .001). Factors associated with in-hospital mortality included older age (≥60 vs <30 years; adjusted odds ratio [aOR], 3.55; 95% CI, 2.34-5.52) and HIV infection (aOR, 1.39; 95% CI, 1.07-1.79). Within waves, patients who were admitted during weeks 5 to 9 had significantly higher odds of being 60 years or older (aOR, 2.09; 95% CI, 1.79-2.45) or having severe COVID-19 at admission (aOR, 2.49; 95% CI, 2.14-2.90) than those admitted during the first 4 weeks. Conclusions and Relevance: The characteristics of admitted patients during the Omicron wave and risk factors for in-hospital mortality in Zambia reflect data reported elsewhere. Within-wave analyses revealed a pattern in which it appeared that admission of higher-risk patients was prioritized during periods when there were surges in demand for health services during COVID-19 waves. These findings support the need to expand health system capacity and improve health system resiliency in Zambia and other countries with resource-limited health systems.

Understanding the role of financial health literacy in midlife and old age: A scoping review.

As global population ageing persists, understanding older adults' capacity to navigate the financial and healthcare system is essential. This scoping review examines how the concept of financial health literacy (FHL) is described and measured in the existing literature, the factors that may affect it, and its potential outcomes in middle-aged and older adults. The review follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) extension guidelines to synthesise the available evidence on this topic. We utilised electronic databases and hand searching to identify relevant literature published between 2010 and 2022. A total of 29 articles were included in this review. The results showed that FHL involved accessing, understanding and utilising financial information for planning/management of healthcare expenses and selecting appropriate health services. However, FHL is not particularly depicted as a concept in the current literature, as most studies investigated health literacy, financial literacy and health insurance literacy as separate domains that were interrelated to one another. No validated measurement tool was developed for FHL. We propose five domains to indicate the concept and measurement of FHL in middle-aged/older adults: money management, management of medical bills, understanding health insurance, deciding on appropriate health services, and planning for long-term care needs. Demographic variables, such as sex (females), advanced age, cognitive impairment, low education and income and racial and ethnic minorities, were found to be related to low FHL. The reviewed studies also showed that FHL was related to several outcomes, including healthcare decision-making, physical health and psychological well-being. Hence, future studies to develop and validate assessment tools of FHL, together with the involvement of vulnerable groups, are imperative to understanding the concept of FHL. This could also facilitate the development of appropriate interventions that could enhance this capacity in the ageing population.

Protecting the gains: analysis of HIV treatment and service delivery programme data and interventions implemented in 19 African countries during COVID-19.

INTRODUCTION: The potential disruption in antiretroviral therapy (ART) services in Africa at the start of the COVID-19 pandemic raised concern for increased morbidity and mortality among people living with HIV (PLHIV). We describe HIV treatment trends before and during the pandemic and interventions implemented to mitigate COVID-19 impact among countries supported by the US Centers for Disease Control and Prevention (CDC) through the President's Emergency Plan for AIDS Relief (PEPFAR). METHODS: We analysed quantitative and qualitative data reported by 10,387 PEPFAR-CDC-supported ART sites in 19 African countries between October 2019 and March 2021. Trends in PLHIV on ART, new ART initiations and treatment interruptions were assessed. Viral load coverage (testing of eligible PLHIV) and viral suppression were calculated at select time points. Qualitative data were analysed to summarize facility- and community-based interventions implemented to mitigate COVID-19. RESULTS: The total number of PLHIV on ART increased quarterly from October 2019 (n = 7,540,592) to March 2021 (n = 8,513,572). The adult population (≥15 years) on ART increased by 14.0% (7,005,959-7,983,793), while the paediatric population (<15 years) on ART declined by 2.6% (333,178-324,441). However, the number of new ART initiations dropped between March 2020 and June 2020 by 23.4% for adults and 26.1% for children, with more rapid recovery in adults than children from September 2020 onwards. Viral load coverage increased slightly from April 2020 to March 2021 (75-78%) and viral load suppression increased from October 2019 to March 2021 (91-94%) among adults and children combined. The most reported interventions included multi-month dispensing (MMD) of ART, community service delivery expansion, and technology and virtual platforms use for client engagement and site-level monitoring. MMD of ≥3 months increased from 52% in October 2019 to 78% of PLHIV ≥ age 15 on ART in March 2021. CONCLUSIONS: With an overall increase in the number of people on ART, HIV programmes proved to be resilient, mitigating the impact of COVID-19. However, the decline in the number of children on ART warrants urgent investigation and interventions to prevent further losses experienced during the COVID-19 pandemic and future public health emergencies.

Farnesoid X receptor agonist tropifexor attenuates cholestasis in a randomised trial in patients with primary biliary cholangitis.

Background & Aims: The safety, tolerability, and efficacy of the non-bile acid farnesoid X receptor agonist tropifexor were evaluated in a phase II, double-blind, placebo-controlled study as potential second-line therapy for patients with primary biliary cholangitis (PBC) with an inadequate ursodeoxycholic acid response. Methods: Patients were randomised (2:1) to receive tropifexor (30, 60, 90, or 150 µg) or matched placebo orally once daily for 28 days, with follow-up on Days 56 and 84. Primary endpoints were safety and tolerability of tropifexor and reduction in levels of γ-glutamyl transferase (GGT) and other liver biomarkers. Other objectives included patient-reported outcome measures using the PBC-40 quality-of-life (QoL) and visual analogue scale scores and tropifexor pharmacokinetics. Results: Of 61 enrolled patients, 11, 9, 12, and 8 received 30-, 60-, 90-, and 150-µg tropifexor, respectively, and 21 received placebo; 3 patients discontinued treatment because of adverse events (AEs) in the 150-µg tropifexor group. Pruritus was the most frequent AE in the study (52.5% [tropifexor] vs. 28.6% [placebo]), with most events of mild to moderate severity. Decreases seen in LDL-, HDL-, and total-cholesterol levels at 60-, 90-, and 150 µg doses stabilised after treatment discontinuation. By Day 28, tropifexor caused 26-72% reduction in GGT from baseline at 30- to 150-µg doses (p <0.001 at 60-, 90-, and 150-µg tropifexor vs. placebo). Day 28 QoL scores were comparable between the placebo and tropifexor groups. A dose-dependent increase in plasma tropifexor concentration was observed, with 5- to 5.55-fold increases in AUC0-8h and Cmax between 30- and 150-µg doses. Conclusions: Tropifexor showed improvement in cholestatic markers relative to placebo, predictable pharmacokinetics, and an acceptable safety-tolerability profile, thereby supporting its potential further clinical development for PBC. Lay summary: The bile acid ursodeoxycholic acid (UDCA) is the standard-of-care therapy for primary biliary cholangitis (PBC), but approximately 40% of patients have an inadequate response to this therapy. Tropifexor is a highly potent non-bile acid agonist of the farnesoid X receptor that is under clinical development for various chronic liver diseases. In the current study, in patients with an inadequate response to UDCA, tropifexor was found to be safe and well tolerated, with improved levels of markers of bile duct injury at very low (microgram) doses. Itch of mild to moderate severity was observed in all groups including placebo but was more frequent at the highest tropifexor dose. Clinical Trials Registration: This study is registered at ClinicalTrials.gov (NCT02516605).

COVID-19 Vaccine Effectiveness Against Progression to In-Hospital Mortality in Zambia, 2021-2022.

Background: Coronavirus disease 2019 (COVID-19) vaccines are highly effective for reducing severe disease and mortality. However, vaccine effectiveness data are limited from Sub-Saharan Africa. We report COVID-19 vaccine effectiveness against progression to in-hospital mortality in Zambia. Methods: We conducted a retrospective cohort study among admitted patients at 8 COVID-19 treatment centers across Zambia during April 2021 through March 2022, when the Delta and Omicron variants were circulating. Patient demographic and clinical information including vaccination status and hospitalization outcome (discharged or died) were collected. Multivariable logistic regression was used to assess the odds of in-hospital mortality by vaccination status, adjusted for age, sex, number of comorbid conditions, disease severity, hospitalization month, and COVID-19 treatment center. Vaccine effectiveness of ≥1 vaccine dose was calculated from the adjusted odds ratio. Results: Among 1653 patients with data on their vaccination status and hospitalization outcome, 365 (22.1%) died. Overall, 236 (14.3%) patients had received ≥1 vaccine dose before hospital admission. Of the patients who had received ≥1 vaccine dose, 22 (9.3%) died compared with 343 (24.2%) among unvaccinated patients (P < .01). The median time since receipt of a first vaccine dose (interquartile range) was 52.5 (28-107) days. Vaccine effectiveness for progression to in-hospital mortality among hospitalized patients was 64.8% (95% CI, 42.3%-79.4%). Conclusions: Among patients admitted to COVID-19 treatment centers in Zambia, COVID-19 vaccination was associated with lower progression to in-hospital mortality. These data are consistent with evidence from other countries demonstrating the benefit of COVID-19 vaccination against severe complications. Vaccination is a critical tool for reducing the consequences of COVID-19 in Zambia.

COVID-19 Vaccine Effectiveness during a Prison Outbreak when Omicron was the Dominant Circulating Variant-Zambia, December 2021.

During a COVID-19 outbreak in a prison in Zambia from December 14 to 19, 2021, a case-control study was done to measure vaccine effectiveness (VE) against infection and symptomatic infection, when the Omicron variant was the dominant circulating variant. Among 382 participants, 74.1% were fully vaccinated, and the median time since full vaccination was 54 days. There were no hospitalizations or deaths. COVID-19 VE against any SARS-CoV-2 infection was 64.8%, and VE against symptomatic SARS-CoV-2 infection was 72.9%. COVID-19 vaccination helped protect incarcerated persons against SARS-CoV-2 infection during an outbreak while Omicron was the dominant variant in Zambia. These findings provide important local evidence that might be used to increase COVID-19 vaccination in Zambia and other countries in Africa.