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Hip fracture care in Zimbabwe : a cohort-based health economic analysis
Get PDFAimsHip fractures are a leading cause of morbidity and mortality worldwide, particularly among older people. While early surgical management improves outcomes compared to non-surgical approaches, high costs of surgery pose significant barriers in low- and middle-income countries. A cost-utility analysis of hip fracture management was undertaken in Zimbabwe, to guide resource allocation and policy.MethodsPatient-level data were obtained from a prospective cohort of adults aged 40 years and above with acute hip fractures presenting to hospital in Harare (two public; five private) between October 2021 and October 2022. Healthcare resource use and costs in 2023 USD1,676 (95% CI 730 to 2,621) higher per patient. The ICER for the primary analysis was 4,126/QALY gained. The results were sensitive to the exchange rate used to estimate costs.ConclusionAlthough patients who underwent surgery for hip fractures had higher costs, they had better health outcomes in terms of QALYs. Targeted improvements in provision of surgical care, particularly in minimizing surgical delays, could improve both patient outcomes and lower healthcare costs
The BMIgap tool to quantify transdiagnostic brain signatures of current and future weight
Get PDFUnderstanding the neurobiological underpinnings of weight gain could reduce excess mortality and improve long-term trajectories of psychiatric disorders. Using brain scans from healthy individuals (n = 1,504), we trained a model to predict body mass index (BMI) and applied it to individuals with schizophrenia (n = 146), clinical high-risk states for psychosis (n = 213) and recent-onset depression (ROD, n = 200). We computed BMIgap (BMIpredicted − BMImeasured), interrogated its brain-level overlaps with schizophrenia and explored whether BMIgap predicted weight gain at the 1-year and 2-year follow-ups. Schizophrenia (BMIgap = 1.05 kg m−2) and clinical high-risk individuals (BMIgap = 0.51 kg m−2) showed increased BMIgap and individuals with ROD (BMIgap = −0.82 kg m−2) showed decreased BMIgap. Shared brain patterns of BMI and schizophrenia were linked to illness duration, disease onset and hospitalization frequency. Higher BMIgap predicted future weight gain, particularly in younger individuals with ROD, and at 2-year follow-up. Here we show that BMIgap can serve as a potential brain-derived measure to stratify at-risk individuals and deliver tailored interventions for better metabolic risk control
Scaling relations, dynamical heating, and tidal disruption in spin s ultralight dark matter models
Get PDFWe explore the impact of spin , spin , and spin ultralight dark matter (ULDM) on small scales by numerically solving the Schrödinger–Poisson system using the time-split method. We perform simulations of ULDM for each spin, starting with different numbers of identical initial solitons and analyse the properties of the resulting haloes after they merge. Our findings reveal that higher spin lead to broader, less dense haloes with more prominent Navarro–Frenk–White (NFW) tails, a characteristic that persists regardless of the number of solitons involved. Additionally, we study the process of dynamical heating for these haloes, and find that the heating time-scale for higher spin increases order of magnitude compared to the spin case. Then, we identify scaling relations that describe the density profile, core-NFW of spin s ULDM haloes as a function of the number of initial solitons . These relations allow us to construct equivalent haloes based on average density or total mass, for arbitrarily large , without having to simulate those systems. We simulate the orbit of an ULDM satellite in a constructed halo treated as an external potential, and find that for host haloes having the same average density, the disruption time of the satellite is as predicted for uniform sphere regardless of the spin. However, satellites orbiting haloes having the same mass for each spin, result in faster disruption in the case of spin , whereas for haloes having the same core size result in faster disruption in the case of spin
Synthetic RNA ligands as activators of type I toxin–antitoxin systems: a novel antimicrobial strategy targeting <i>Helicobacter pylori</i>
Get PDFTargeting RNAs with synthetic small molecules represents a privileged avenue for the discovery of new therapeutic approaches and offers the possibility to identify original targets escaping the classical rules of druggability and resistance. In the context of multidrug resistance to antibiotics, an urgent need for new antimicrobial compounds is emerging; however both academia and industry are mostly working on known extensively explored targets susceptible to inducing resistance again. In this work, we present a new potential target for antibiotics represented by a Helicobacter pylori type I toxin-antitoxin system where RNA-RNA interactions are responsible for silencing the synthesis of a toxin that is lethal to bacteria and that is activated only under particular conditions. We report the design and synthesis of new RNA binders to inhibit these RNA-RNA interactions and to artificially activate toxin production and kill bacteria. After screening these compounds using several complementary assays, we identified a selective inhibitor of the targeted RNA-RNA interaction showing specific antibiotic activity against H. pylori. This represents an unprecedented antimicrobial strategy based on the use of compounds that are not toxic by themselves but activate the production of an endogenous toxin produced by the bacteria themselves. Finally, this work allowed us to explore new compounds to inhibit RNA-RNA interactions, which also represents an underexplored field of RNA targeting
“You feel like you come up short over and over again”: a qualitative study of provider perspectives of barriers to respectful maternity care in Boston
Get PDFAbstract Background Respectful maternity care is a human right. Disrespect in childbirth has been implicated in adverse maternal and child outcomes globally, including in the United States. Up to 30% of U.S. birthing people report being disrespected when giving birth, with reported rates being higher amongst racial/ethnic minorities and those who do not primarily speak English. Disrespect in childbirth leads to increased rates of postpartum depression and lower healthcare utilization. Methods Semi-structured qualitative interviews were conducted with 18 maternity health care providers at Massachusetts General Hospital in Boston, Massachusetts. Respondents included physicians, midwives, and nurses. Transcripts of the interviews were coded using an inductive approach, and themes were developed from the codes. Results Four major themes emerged: (1) patient-provider communication and dynamics, (2) structural and organizational drivers of care, (3) patterns in disrespect, and (4) clinician knowledge and beliefs about respectful and disrespectful care. Key barriers to respectful care included workload, facility infrastructure, and constraints in the provision of clinical care. Providers perceived that certain social vulnerabilities (e.g., race, age, ethnicity, language) predisposed some patients to greater levels of disrespect. Consent processes and procedures were also identified to be a crucial leverage point in preventing disrespectful maternity care. Conclusion Although respondents generally perceived care to be of high quality, they noted that challenges to respectful maternity care are present even in high-resource settings. Future research in disrespect and abuse in maternity care is necessary to further develop sustainable solutions. It is imperative to continue exploring the perspectives of maternity care providers, as they are key stakeholders and are uniquely positioned to identify root causes of mistreatment in care provisio
Health Care Providers&#8217; Perceptions of Respectful and Disrespectful Maternity Care in Facility-Based Births Worldwide: A Mixed Methods Systematic Review
Get PDFThe role of antimicrobial prophylaxis in the management of snakebite: a systematic review
Get PDFBackgroundSnakebite, a neglected tropical disease disproportionately affecting lower-income countries, is a significant cause of morbidity and mortality worldwide. Local toxicity and necrosis may result in secondary bacterial infection of bite sites. Despite most guidelines not recommending prophylactic antimicrobials, their use is common in practise. This review aims to systematically assess literature around the use of prophylactic use of antimicrobials in snakebite. We also aim to assess the incidence of secondary infections, types of antimicrobials used, and the aetiology of infections arising from snakebite.MethodsSystematic database searches for studies assessing prophylactic antimicrobial use undertaken. Data was assessed by two reviewers and extracted using a standardised proforma. Included studies were assessed for risk of bias and data extracted narratively. The protocol was prospectively registered on PROSPERO database (CRD42023430752).Results492 studies were screened. Four met the inclusion criteria, totaling 696 patients across three countries. No study found a statistically significant benefit for the use of antibiotic prophylaxis, with no effect on the number or severity of adverse incidents. There were 114 adverse incidences related to secondary infection, with nineteen positive cultures.ConclusionsThis review finds little evidence pertaining to the use of antimicrobial prophylaxis. Studies were highly heterogenous with incomplete reporting of standardised processes. Bacteria isolated supports existing observational data implicating bacteria found in snake oral flora (e.g. M. morganii and Enterococcus spp). This is an important consideration when deciding empirical antimicrobial regimens for suspected superadded infection. International consensus is required to define infection following snakebite and further high-quality research is required to draw definitive conclusions regarding antimicrobial prophylaxis
CO2e (best) avoided? How people experience CO2e avoided on the Too Good To Go app
Get PDFCarbon Dioxide Equivalent (CO2e) avoided is increasingly communicated to individuals through digital media. Too Good To Go – a food waste app – presents users with a personalised CO2e avoided figure. Each time they collect food from a supermarket, café or restaurant their number increases. How do users experience CO2e avoided on the app? We explore this question through a longitudinal research project with 10 households in Oxfordshire, involving three interviews, five self-report surveys and a 28-day trial of the app. In general, participants did not see the figure as particularly valuable – best demonstrated in how little it influenced their usage of the app. This was largely due to issues of truthfulness. Each time a participant travelled and collected a bag, the CO2e avoided data point would increase by a fixed amount. This was at odds with the considerable variation in user experiences. Instead of CO2e avoided, participants put forward alternative impact data that was less individualised and more relatable. We use the concept of data experiences, as developed by Hoeyer et al. (2024), to think through the findings. In doing so, we provide empirical support to the utility of the four-part concept and put forward an additional cross-cutting theme of intensity. The paper also highlights how organisations cannot assume that certain metrics will influence peoples’ opinions and behaviours. To have an impact, their audiences’ data experiences need to be properly understood
Impact of drug-resistance diagnosis based on whole-genome sequencing on the treatment adequacy of patients with drug-resistant pulmonary tuberculosis in the state of São Paulo, Brazil: a protocol for a non-randomised controlled trial (Gen-TB PróCura)
Get PDFIntroduction: Since 2018, WHO has endorsed the use of whole-genome sequencing (WGS) of Mycobacterium tuberculosis complex isolates to detect drug-resistant tuberculosis (DR-TB). This endorsement was based on the assumption that a faster and more detailed description of the resistance profile would improve treatment prescription for DR-TB by healthcare providers, and hence the treatment outcomes of patients. Nonetheless, this assumption has not been tested in routine clinical practice and different scenarios. In Brazil, WGS is not routinely used for the diagnosis of DR-TB, having been carried out in only a few centres for research purposes. With this trial, we will evaluate whether a WGS-based drug-resistance report improves treatment adequacy in patients with pulmonary DR-TB, compared with the current standard-of-care diagnostic methods used in the state of São Paulo, Brazil. Methods and analysis: We will conduct a non-randomised controlled clinical trial with two arms to compare the intervention group (ie, individuals receiving a WGS-based report) with a historical control group (i.e., individuals who received resistance diagnostics based on the standard of care of conventional genotyping and phenotyping techniques). The primary outcome will be the proportion of patients whose treatment scheme was adequate based on complete resistance profile determined by WGS and/or phenotypic drug-susceptibility testing (pDST). Other secondary outcomes will also be considered. The target sample size is 88 eligible patients per group. The intervention group will be prospectively recruited over 18 months and the control group will be composed of patients diagnosed with pulmonary DR-TB up to 2 years before the start of the trial. To ensure comparability, isolates from the control group will undergo WGS retrospectively, and pDST will be performed retrospectively in both groups. This clinical trial will take place in six medical centres for the treatment of DR-TB in the state of São Paulo. This study is intended to support the implementation of the WGS in the routine diagnosis of DR-TB in the state of São Paulo. Ethics and dissemination: Ethical approval was obtained from the Human Research Committee of the Institute of Biomedical Sciences, University of São Paulo, Brazil (CAAE: 79497924.1.1001.5467). Study results will be published in peer-reviewed journals and disseminated to policymakers and stakeholders. Trial registration number: U1111-1308-4669
