Non-fatal injuries in rural Burkina Faso amongst older adults, disease burden and health system responsiveness:a cross-sectional household survey

OBJECTIVES: This study aimed to evaluate the epidemiology of injury as well as patient-reported health system responsiveness following injury and how this compares with non-injured patient experience, in older individuals in rural Burkina Faso. DESIGN: Cross-sectional household survey. Secondary analysis of the CRSN Heidelberg Ageing Study dataset. SETTING: Rural Burkina Faso. PARTICIPANTS: 3028 adults, over 40, from multiple ethnic groups, were randomly sampled from the 2015 Nouna Health and Demographic Surveillance Site census. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was incidence of injury. Secondary outcomes were incidence of injury related disability and patient-reported health system responsiveness following injury. RESULTS: 7.7% (232/3028) of the population reported injury in the preceding 12 months. In multivariable analyses, younger age, male sex, highest wealth quintile, an abnormal Generalised Anxiety Disorder score and lower Quality of Life score were all associated with injury. The most common mechanism of injury was being struck or hit by an object, 32.8%. In multivariable analysis, only education was significantly negatively associated with odds of disability (OR 0.407, 95% CI 0.17 to 0.997). Across all survey participants, 3.9% (119/3028) reported their most recent care seeking episode was following injury, rather than for another condition. Positive experience and satisfaction with care were reported following injury, with shorter median wait times (10 vs 20 min, p=0.002) and longer consultation times (20 vs 15 min, p=0.002) than care for another reason. Injured patients were also asked to return to health facilities more often than those seeking care for another reason, 81.4% (95% CI 73.1% to 87.9%) vs 54.8% (95% CI 49.9% to 53.6%). CONCLUSIONS: Injury is an important disease burden in this older adult rural low-income and middle-income country population. Further research could inform preventative strategies, including safer rural farming methods, explore the association between adverse mental health and injury, and strengthen health system readiness to provide quality care

Is there scope for cost savings and efficiency gains in HIV services? A systematic review of the evidence from low- and middle-income countries.

OBJECTIVE: To synthesize the data available--on costs, efficiency and economies of scale and scope--for the six basic programmes of the UNAIDS Strategic Investment Framework, to inform those planning the scale-up of human immunodeficiency virus (HIV) services in low- and middle-income countries. METHODS: The relevant peer-reviewed and "grey" literature from low- and middle-income countries was systematically reviewed. Search and analysis followed Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. FINDINGS: Of the 82 empirical costing and efficiency studies identified, nine provided data on economies of scale. Scale explained much of the variation in the costs of several HIV services, particularly those of targeted HIV prevention for key populations and HIV testing and treatment. There is some evidence of economies of scope from integrating HIV counselling and testing services with several other services. Cost efficiency may also be improved by reducing input prices, task shifting and improving client adherence. CONCLUSION: HIV programmes need to optimize the scale of service provision to achieve efficiency. Interventions that may enhance the potential for economies of scale include intensifying demand-creation activities, reducing the costs for service users, expanding existing programmes rather than creating new structures, and reducing attrition of existing service users. Models for integrated service delivery--which is, potentially, more efficient than the implementation of stand-alone services--should be investigated further. Further experimental evidence is required to understand how to best achieve efficiency gains in HIV programmes and assess the cost-effectiveness of each service-delivery model

COVID-19 vaccine uptake, confidence and hesitancy in rural KwaZulu-Natal, South Africa between April 2021 and April 2022: A continuous cross-sectional surveillance study

High COVID-19 vaccine hesitancy in South Africa limits protection against future epidemic waves. We evaluated how vaccine hesitancy and its correlates evolved April 2021-April 2022 in a well-characterized rural KwaZulu-Natal setting. All residents aged >15 in the Africa Health Research Institute's surveillance area were invited to complete a home-based, in-person interview. We described vaccine uptake and hesitancy trends, then evaluated associations with pre-existing personal factors, dynamic environmental context, and cues to action using ordinal logistic regression. Among 10,011 respondents, vaccine uptake rose as age-cohorts became vaccine-eligible before levelling off three months post-eligibility; younger age-groups had slower uptake and plateaued faster. Lifetime receipt of any COVID-19 vaccine rose from 3.0% in April-July 2021 to 32.9% in January-April 2022. Among 7,445 unvaccinated respondents, 47.7% said they would definitely take a free vaccine today in the first quarter of the study time period, falling to 32.0% in the last. By March/April 2022 only 48.0% of respondents were vaccinated or said they would definitely would take a vaccine. Predictors of lower vaccine hesitancy included being male (adjusted odds ratio [aOR]: 0.70, 95% confidence interval [CI]: 0.65-0.76), living with vaccinated household members (aOR:0.65, 95%CI: 0.59-0.71) and knowing someone who had had COVID-19 (aOR: 0.69, 95%CI: 0.59-0.80). Mistrust in government predicted greater hesitancy (aOR: 1.47, 95%CI: 1.42-1.53). Despite several COVID-19 waves, vaccine hesitancy was common in rural South Africa, rising over time and closely tied to mistrust in government. However, interpersonal experiences countered hesitancy and may be entry-points for interventions

Is learning being supported when information is provided to informal carers during inpatient stroke rehabilitation? A qualitative study

Purpose: To explore how health professionals provide information to informal carers during inpatient stroke rehabilitation and whether these practices align with adult learning principles. Methods: Informal carers and survivors of stroke who had completed inpatient rehabilitation, and health professionals working in inpatient stroke rehabilitation were interviewed. Directed qualitative content analysis was conducted using an adult learning model, to determine how closely reported practices aligned to adult learning principles. Results: 14 carers, 6 survivors of stroke and 17 health professionals participated. Carers (79% female, 57% spouse/partner) reported having incomplete knowledge during rehabilitation, lacking information about mechanisms of stroke recovery, rehabilitation processes, long-term effects of stroke, and navigating post-discharge services. Health professionals supported carers to address their learning needs related to safety of caring for stroke survivors. Carers indicated they were responsible for their own non-safety related learning. Health professionals tended not to check carers’ understanding of information provided nor offer learning opportunities beyond written or verbal information. Conclusions: Health professionals consistently provide certain information to carers during inpatient rehabilitation, but adult learning principles are not routinely applied when information is provided. Fostering adult learning among informal carers may improve preparedness of carers to support stroke survivors after discharge from inpatient rehabilitation. © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group

Dual pathogenicity island transfer by piggybacking lateral transduction

Lateral transduction (LT) is the process by which temperate phages mobilize large sections of bacterial genomes. Despite its importance, LT has only been observed during prophage induction. Here, we report that superantigen-carrying staphylococcal pathogenicity islands (SaPIs) employ a related but more versatile and complex mechanism of gene transfer to drive chromosomal hypermobility while self-transferring with additional virulence genes from the host. We found that after phage infection or prophage induction, activated SaPIs form concatamers in the bacterial chromosome by switching between parallel genomic tracks in replication bubbles. This dynamic life cycle enables SaPIbov1 to piggyback its LT of staphylococcal pathogenicity island vSaα, which encodes an array of genes involved in host-pathogen interactions, allowing both islands to be mobilized intact and transferred in a single infective particle. Our findings highlight previously unknown roles of pathogenicity islands in bacterial virulence and show that their evolutionary impact extends beyond the genes they carry

PROTAC-mediated degradation of Bruton's tyrosine kinase is inhibited by covalent binding

The impact of covalent binding on PROTAC-Mediated degradation of BTK was investigated through the preparation of both covalent binding and reversible binding PROTACs derived from the covalent BTK inhibitor ibrutinib. It was determined that a covalent binding PROTAC inhibited BTK degradation despite evidence of target engagement, while BTK degradation was observed with a reversible binding PROTAC. These observations were consistently found when PROTACs that were able to recruit either IAP or cereblon E3 ligases were employed. Proteomics analysis determined that the use of a covalently bound PROTAC did not result in the degradation of covalently bound targets, while degradation was observed for some reversibly bound targets. This observation highlights the importance of catalysis for successful PROTAC-Mediated degradation and highlights a potential caveat for the use of covalent target binders in PROTAC design

Closing in on Asymmetric Dark Matter I: Model independent limits for interactions with quarks

It is argued that experimental constraints on theories of asymmetric dark matter (ADM) almost certainly require that the DM be part of a richer hidden sector of interacting states of comparable mass or lighter. A general requisite of models of ADM is that the vast majority of the symmetric component of the DM number density must be removed in order to explain the observed relationship $\Omega_B\sim\Omega_{DM}$ via the DM asymmetry. Demanding the efficient annihilation of the symmetric component leads to a tension with experimental limits if the annihilation is directly to Standard Model (SM) degrees of freedom. A comprehensive effective operator analysis of the model independent constraints on ADM from direct detection experiments and LHC monojet searches is presented. Notably, the limits obtained essentially exclude models of ADM with mass 1GeV$\lesssim m_{DM} \lesssim$ 100GeV annihilating to SM quarks via heavy mediator states. This motivates the study of portal interactions between the dark and SM sectors mediated by light states. Resonances and threshold effects involving the new light states are shown to be important for determining the exclusion limits.Comment: 18+6 pages, 18 figures. v2: version accepted for publicatio

Access to primary healthcare during lockdown measures for COVID-19 in rural South Africa: an interrupted time series analysis.

OBJECTIVES: We evaluated whether implementation of lockdown orders in South Africa affected ambulatory clinic visitation in rural Kwa-Zulu Natal (KZN). DESIGN: Observational cohort SETTING: Data were analysed from 11 primary healthcare clinics in northern KZN. PARTICIPANTS: A total of 46 523 individuals made 89 476 clinic visits during the observation period. EXPOSURE OF INTEREST: We conducted an interrupted time series analysis to estimate changes in clinic visitation with a focus on transitions from the prelockdown to the level 5, 4 and 3 lockdown periods. OUTCOME MEASURES: Daily clinic visitation at ambulatory clinics. In stratified analyses, we assessed visitation for the following subcategories: child health, perinatal care and family planning, HIV services, non-communicable diseases and by age and sex strata. RESULTS: We found no change in total clinic visits/clinic/day at the time of implementation of the level 5 lockdown (change from 90.3 to 84.6 mean visits/clinic/day, 95% CI -16.5 to 3.1), or at the transitions to less stringent level 4 and 3 lockdown levels. We did detect a >50% reduction in child healthcare visits at the start of the level 5 lockdown from 11.9 to 4.7 visits/day (-7.1 visits/clinic/day, 95% CI -8.9 to 5.3), both for children aged <1 year and 1-5 years, with a gradual return to prelockdown within 3 months after the first lockdown measure. In contrast, we found no drop in clinic visitation in adults at the start of the level 5 lockdown, or related to HIV care (from 37.5 to 45.6, 8.0 visits/clinic/day, 95% CI 2.1 to 13.8). CONCLUSIONS: In rural KZN, we identified a significant, although temporary, reduction in child healthcare visitation but general resilience of adult ambulatory care provision during the first 4 months of the lockdown. Future work should explore the impacts of the circulating epidemic on primary care provision and long-term impacts of reduced child visitation on outcomes in the region

Long-Term Costs and Health Impact of Continued Global Fund Support for Antiretroviral Therapy

Background: By the end of 2011 Global Fund investments will be supporting 3.5 million people on antiretroviral therapy (ART) in 104 low- and middle-income countries. We estimated the cost and health impact of continuing treatment for these patients through 2020. Methods and Findings: Survival on first-line and second-line ART regimens is estimated based on annual retention rates reported by national AIDS programs. Costs per patient-year were calculated from country-reported ARV procurement prices, and expenditures on laboratory tests, health care utilization and end-of-life care from in-depth costing studies. Of the 3.5 million ART patients in 2011, 2.3 million will still need treatment in 2020. The annual cost of maintaining ART falls from $1.9 billion in 2011 to$1.7 billion in 2020, as a result of a declining number of surviving patients partially offset by increasing costs as more patients migrate to second-line therapy. The Global Fund is expected to continue being a major contributor to meeting this financial need, alongside other international funders and domestic resources. Costs would be $150 million less in 2020 with an annual 5$150-370 million less with a 5%-12% annual decline in second-line prices, but $200 million higher in 2020 with phase out of stavudine (d4T), or$200 million higher with increased migration to second-line regimens expected if all countries routinely adopted viral load monitoring. Deaths postponed by ART correspond to 830,000 life-years saved in 2011, increasing to around 2.3 million life-years every year between 2015 and 2020. Conclusions: Annual patient-level direct costs of supporting a patient cohort remain fairly stable over 2011-2020, if current antiretroviral prices and delivery costs are maintained. Second-line antiretroviral prices are a major cost driver, underscoring the importance of investing in treatment quality to improve retention on first-line regimens