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Time to turn off the toxins: adjuvant suppression of group A streptococcus.
Get PDFStreptococcus pyogenes, or group A streptococcus, remains a major global pathogen, responsible for a wide spectrum of diseases ranging from pharyngitis to severe invasive group A streptococcus (iGAS) infections. Central to the virulence of S pyogenes are its many anti-phagocytic proteins and toxins, including the superantigens. Emergence of new S pyogenes lineages are associated with both increased iGAS case frequency and mortality, often linked to changes in toxin production
General practice characteristics associated with pay-for-performance in the UK: a systematic review.
Get PDFBACKGROUND: The Quality and Outcomes Framework (QOF), a pay-for-performance programme, has been the most widespread quality initiative in NHS general practice since 2004. It has contributed between 25% and 8% of practices' income during this time, but concerns about its effect on equity have been raised. AIM: To understand which practice characteristics are associated with QOF performance. DESIGN AND SETTING: A systematic review was conducted, focusing on NHS general practice in the UK. METHOD: MEDLINE, Embase, CINAHL+, Web of Science, and grey literature were searched for studies examining the association between general practice characteristics and QOF performance. RESULTS: Twenty-two studies, published between 2006 and 2022, exploring the relationship between six population and 15 organisational characteristics and QOF measures were found. Most studies were cross-sectional, of English general practices, and used data from the early years of QOF. A negative association was frequently found between overall QOF performance and socioeconomic deprivation; increasing proportion of registered patients aged >65 years; increasing list size; increasing mean GP age; and Alternative Provider Medical Services contracts. Group practices (versus single-handed), more full-time equivalent (FTE) GPs, and being a training practice were frequently associated with better overall QOF performance. The associations of most other characteristics with performance were inconsistent. CONCLUSION: Associations with characteristics both within and outside practices' control were identified. Pay-for-performance instruments may systematically disadvantage practices serving those at greatest risk of ill-health such as older and more deprived populations. Given the cross-sectional design of many studies and focus on the early years of QOF, more up-to-date evidence is needed to understand if and why these relationships persist
Modelling the epidemiological and economic impact of digital adherence technologies with differentiated care for tuberculosis treatment in Ethiopia.
Get PDFBACKGROUND: Digital adherence technologies (DATs) with associated differentiated care are potential tools to improve tuberculosis (TB) treatment outcomes and reduce associated costs for both patients and healthcare providers. However, the balance between epidemiological and economic benefits remains unclear. Here, we used data from the ASCENT trial to estimate the potential long-term epidemiological and economic impact of DAT interventions in Ethiopia. METHODS: We developed a compartmental transmission model for TB, calibrated to Ethiopia and parameterised with patient and provider costs. We compared the epidemiological and economic impact of two DAT interventions, a digital pillbox and medication labels, to the current standard of care, assuming each was introduced at scale in 2023. We projected long-term TB incidence, mortality and costs to 2035 and conducted a threshold analysis to identify the maximum possible epidemiological impact of a DAT intervention by assuming 100% treatment completion for patients on DAT. FINDINGS: We estimated small and uncertain epidemiological benefits of the pillbox intervention compared with the standard of care in Ethiopia, with a difference of -0.4% (95% uncertainty interval (UI) -1.1%; +2.0%) incident TB episodes and -0.7% (95% UI -2.2%; +3.6%) TB deaths. However, our analysis also found large total provider and patient cost savings (US118; US3 (95%UI: US5), respectively, over 2023-2035), translating to a 50.2% (95% UI 35.9%; 65.2%) reduction in total cost of treatment. Results were similar for the medication label intervention. The maximum possible epidemiological impact a theoretical DAT intervention could achieve over the same timescale would be a 3% (95% UI 1.4%; 5.5%) reduction in incident TB and an 8.2% (95% UI 4.4%; 12.8%) reduction in TB deaths. INTERPRETATION: DAT interventions, while showing limited epidemiological impact, could substantially reduce TB treatment costs for both patients and the healthcare provider
Ethical issues in vaccine trial participation by adolescents: qualitative insights on family decision making from a human papillomavirus vaccine trial in Tanzania.
Get PDFBACKGROUND: Research in children is essential for them to benefit from the outcomes of research but involvement must be weighed against potential harms. In many countries and circumstances, medical research legally requires parental consent until the age of 18 years, with poorly defined recommendations for assent prior to this. However, there is little research exploring how these decisions are made by families and the ethical implications of this. AIM: To explore key ethical debates in decision-making for participation of children and adolescents in a human papillomavirus (HPV) vaccine trial. METHODS: Semi-structured interviews were undertaken with Tanzanian girls (aged 9-16 years) who had participated in an HPV vaccine trial (n = 13), their parents or guardians (n = 12), and girls together with their parents (in paired parent-child interviews) (n = 6). The interviews were analysed using thematic analysis. Interview data came from a qualitative acceptability study undertaken as part of the Dose Reduction Immunobridging and Safety Study of Two Human Papillomavirus (HPV) Vaccines in Tanzanian Girls (DoRIS) trial. RESULTS: Girls and parents desired collaborative decision-making, with parents ultimately making the decision to consent. However, girls wanted a larger part in decision-making. Decisions to consent involved many people, including extended social networks, the trial team, media outlets and healthcare professionals and this resulted in conflicts to be negotiated. Deciding where to place trust was central in participants and parents considering decisions to consent and overcoming rumours about trial involvement. CONCLUSIONS: Existing models of decision-making help to understand dynamics between parents, adolescents and researchers but neglect the important wider social impacts and the fundamental nature of trust. Children's roles in discussions can be evaluated using the principles of consent: autonomy, freedom and information. Concepts such as relational autonomy help to explain mechanisms families use to negotiate complex consent decisions. Whilst interviewees supported the maintenance of legal parental consent, researchers must design consent processes centring the child to ensure that whole family decision-making processes are supported
From policy to practice: Experiences from the ECHO trial following revisions of the WHO medical eligibility criteria for contraceptive use (MEC) guidance on DMPA-IM.
Get PDFOBJECTIVES: In 2017, the World Health Organization (WHO) medical eligibility criteria (MEC) for contraception category for intramuscular depot medroxyprogesterone acetate (DMPA-IM) was changed from MEC category 1 to 2 for women at high risk of HIV acquisition. We assessed the impact of communicating this category change among women in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial. STUDY DESIGN: ECHO was conducted in eSwatini, Kenya, South Africa and Zambia. Women were randomized (1:1:1) to DMPA-IM, levonorgestrel (LNG) implant or copper intrauterine device (Cu IUD). We compared the hazards of DMPA-IM discontinuation and assessed sexual behavior and DMPA-IM satisfaction before and after MEC category change. RESULTS: In DMPA-IM users there was a decrease in the hazards of discontinuation after the MEC change (hazard ratio 0.37; 95% CI = 0.26-0.52, p < 0.001). No evidence of an effect of the MEC change was observed in sexual behaviour outcomes. There was some evidence of an increase in disatisfaction with DMPA-IM immediately after the MEC change, with the odds of women reporting a higher score (more dissatisfied) increasing by 1.38 compared with before the MEC change (95% CI = 1.11-1.72). CONCLUSIONS: While counseling on possible theoretical risks associated with contraceptive methods in the MEC is an important medical ethical standard, in this study it did not adversely impact continuation or sexual behavior, while there was some evidence on increase in dissatisfaction. There is however a need to monitor how changes in MEC categories are implemented. IMPLICATIONS: Although we found no evidence in this analysis of an effect of the MEC change on any of the sexual behavioral outcomes among women after the change in category, it is still an important medical ethical standard to counsel on possible theoretical risks associated with contraceptive methods. Given the challenges of translating research findings to guidelines and further to counseling messages, evaluation of clinical guidelines implementation is necessary to understand the effects of implementation and to monitor both intended impacts and unintended consequences
Perceptions of stakeholders on the use of a simplified, combined protocol for treatment of acute malnutrition in Central African Republic.
Get PDFTreatment of acute malnutrition requires novel approaches to improve coverage, reduce costs and improve the efficiency of standard protocols that separate the management of moderate acute malnutrition (MAM) and severe acute malnutrition (SAM). The use of simplified, combined protocols to treat both MAM and SAM has drawn research and policy interest among global, regional and national stakeholders. However, the perspectives of local communities and health care workers regarding the use of protocols to treat acute malnutrition in a routine health care system are generally lacking. This was a cross-sectional mixed-methods study aimed at assessing the perceptions of different stakeholders on the use of a simplified, combined protocol in two districts in the Central African Republic. Most of the respondents preferred the simplified, combined protocol over the standard protocol. They generally agreed that the protocol was easy to understand, allowed more children to receive treatment and was effective in treating acute malnutrition. The protocol modifications were well received, including the expanded admission criteria, use of mid-upper arm circumference (MUAC) only for admission and discharge criteria and reduced and simplified ready-to-use therapeutic food quantity to treat MAM and SAM. Some caregivers expressed concern with the use of MUAC only to declare recovery, flagging that underlying illnesses could still be present. The caregivers recommended the provision of other food basket interventions to improve the treatment. The support by caregivers and health care workers on the idea of training community health volunteers to treat acute malnutrition points to the potential of scaling up decentralized treatment to increase coverage in remote areas
Evaluation of population immunity against SARS-CoV-2 variants, EG.5.1, FY.4, BA.2.86, JN.1, JN.1.4, and KP.3.1.1 using samples from two health demographic surveillance systems in Kenya.
Get PDFIncreased immune evasion by emerging and highly mutated SARS-CoV-2 variants is a key challenge to the control of COVID-19. The majority of these mutations mainly target the spike protein, allowing the new variants to escape the immunity previously raised by vaccination and/or infection by earlier variants of SARS-CoV-2. In this study, we investigated the neutralizing capacity of antibodies against emerging variants of interest circulating between May 2023 and October 2024 using sera from representative samples of the Kenyan population. From our genomics data, we identified the most prevalent Kenyan and global variants and performed pseudoviruses neutralization assays with the most recent SARS-CoV-2 variants. Our data show that antibodies from individuals in the general population in Kenya were less effective against the recent prevalent SARS-CoV-2 omicron variants (i.e. EG.5.1, FY.4, BA.2.86, JN.1, JN.1.4, and KP.3.1.1) compared to the ancestral wildtype strain. Although there was increased neutralization following multiple doses of vaccine, antibodies from > 40% of the vaccinated individuals did not neutralize the omicron variants, suggesting that individuals were susceptible to infection by these variants
Decision-making for childhood vaccination in crisis settings: a survey of practice & barriers.
Get PDFBACKGROUND: Children, particularly those who have received no routine vaccinations (zero-dose children), are at high risk of vaccine-preventable diseases in humanitarian crisis settings. However, the decision-making processes underlying vaccine intervention design and delivery in such settings are poorly understood. The present study investigated the decision-making practices of organisations involved in childhood vaccination in humanitarian crisis settings globally via an online survey. METHODS: Individuals involved in the design or delivery of childhood vaccination programmes in humanitarian crisis settings were invited to fill out a self-administered online survey. Respondents were asked about factors influencing intervention design and vaccine delivery; use of technical guidance, specifically the WHO decision-making framework for vaccination in acute humanitarian emergencies (WHO Framework); and practices for reaching zero-dose children. RESULTS: Fourteen responses were received. Large international organisations and UN agencies were overrepresented in the sample. Technical guidance was considered of high importance when designing vaccine interventions. However, the WHO Framework is not available in relevant languages and has not been well-distributed to local and national actors. Awareness of initiatives to reach zero-dose children was high within our sample, though this may not accurately reflect global awareness. Security and resource availability were key barriers to vaccine delivery and reaching zero-dose children. Problems with vaccine access in our sample pertained primarily to issues with the procurement system rather than vaccine cost. CONCLUSIONS: The WHO Framework should be provided in more languages, and vaccination actors at local and national level should be engaged to improve its practicality and increase awareness of its aims. In order to reach zero-dose children, vaccines must be made available for use in expanded age groups, which is sometimes not currently feasible within the Gavi/UNICEF procurement system. Clarifying this policy would allow relevant organisations to reach more zero-dose children. Additionally, security is a key barrier impeding vaccine delivery, including for zero-dose children. Safe operational space for humanitarian actors in conflict must be maintained and global conflict resolution mechanisms improved
Municipality assessment of temperature-related mortality risks in Norway.
Get PDFBACKGROUND & AIM: Understanding local vulnerability to heat and cold is crucial for public health planning, yet few studies have provided a nationwide analysis of temperature-related mortality across diverse communities. This study analyses the association between ambient air temperature and non-accidental mortality across mainland Norway, using a constrained hierarchical clustering algorithm to group municipalities with similar geographic, environmental, socioeconomic, and demographic patterns. METHODS: This study analysed the association between ambient air temperature and non-accidental mortality across 356 Norwegian municipalities, using daily data from 1996 to 2018. We applied a case time series design with distributed lag non-linear models. A downscaling procedure assessed the effect of 21 vulnerability factors on temperature-related mortality risks, using Principal Components Analysis to explore heterogeneity across clusters. FINDINGS: Cold temperatures contributed to an estimated 3879 deaths per year (95% CI 3718-4130), while heat was associated with 44 deaths annually (95%CI: 29-58). The highest heat-related mortality risk occurred in the South-East, and the highest cold-related risk in the Central-East. Greater heat-related mortality correlated with medium-to sparsely-populated areas, while higher education levels were linked to reduced vulnerability to both heat and cold. INTERPRETATION: By providing the first comprehensive assessment of temperature-related excess mortality and associated risk factors in Norway, our findings underscore the need for targeted, equitable health policies that integrate environmental and socioeconomic factors. These insights are essential to guide climate adaptation strategies, prioritising vulnerable rural communities and socioeconomically disadvantaged groups to mitigate future climate-related health impacts
