Search results
Found 12972 matches for
Age- and sex-specific incidence rates and future projections for hip fractures in Zimbabwe.
INTRODUCTION: Population ageing in Africa is increasing healthcare demands. Hip fractures require multidisciplinary care and are considered an indicator condition for age-related health services. We aimed to estimate current hip fracture incidence in Zimbabwe, compare rates against other regional estimates and estimate future fracture numbers. METHODS: All hip fracture cases in adults aged ≥40 years, presenting to any hospital in Harare over 2 years, were identified. From this, age- and sex-specific hip fracture incidence rates per 100 000 person-years were estimated using 2022 Zimbabwean Census data and compared with South African and Botswanan estimates. Furthermore, using the United Nations population projections, future hip fracture numbers were estimated to 2052 for Zimbabwe. RESULTS: In 2022, 1 83 312 women and 1 79 212 men aged ≥40 years were living in Harare (14.9% of the city's population). Over 2 years 243 hip fracture cases, 133 (54.7%) female, mean (SD) age 71.2 (15.9) years, were identified. Most presented to public hospitals (202 [83.1%]) and were fragility hip fractures (211 [86.8%]); high-impact trauma (eg, traffic accidents) was more common in younger men. Presentation delays of >2 weeks were common (37.4%). Incidence rates for adults aged ≥40 years in Harare (observed) and Zimbabwe (estimated) were 33.5 and 53.8/100 000 person-years, respectively. Over age 50, rates increased with age, with the highest rates seen in women aged ≥85 years (704/100 000 person-years). Age-standardised hip fracture incidence rates are broadly comparable between Zimbabwe, Botswana and Black South Africans in those aged 40-69 years; thereafter, rates in Zimbabwean women and men exceed those in Botswana and South Africa. Across Zimbabwe, the number of hip fractures occurring annually is expected to increase more than 2.5-fold from 1709 in 2022 to 4414 by 2052. CONCLUSION: In Zimbabwe, most hip fractures in adults ≥50 years are fragility fractures, consistent with age-associated osteoporosis; incidence rates exceed those previously reported regionally. Demands on already challenged healthcare systems will increase.
Fractures in sub-Saharan Africa: epidemiology, economic impact and ethnography (Fractures-E 3): study protocol.
Background: The population of older adults is growing in sub-Saharan Africa. Ageing exponentially increases fragility fracture risk. Of all global regions, Africa is projected to observe the greatest increase in fragility fractures. Fractures cause pain, disability and sometimes death, and management is expensive, often requiring complex healthcare delivery. For countries to plan future healthcare services, understanding is needed of fracture epidemiology, associated health service costs and the currently available healthcare resources. Methods:The Fractures-E 3 5-year mixed-methods research programme will investigate the epidemiology, economic impact, and treatment provision for fracture and wider musculoskeletal health in The Gambia, South Africa and Zimbabwe. These three countries are diverse in their geography, degree of urbanisation, maturity of health service infrastructure, and health profiles. The programme comprises five study types: (i) population-based cross-sectional studies to determine vertebral fracture prevalence. Secondary outcomes will include osteoarthritis and sarcopenia. Age- and sex-stratified household sampling will recruit 5030 adults aged 40 years and older; (ii) prospective cohort studies in adults aged 40 years and older will determine hip fracture incidence, associated risk factors, and outcomes over one year ( e.g. mortality, disability, health-related quality of life); (iii) economic studies of direct health costs of hip fracture with projection modelling of future national health costs and cost-effectiveness analyses of different hip fracture care pathways; (iv) national surveys of hip fracture services (including traditional bonesetters in The Gambia); and (v) ethnographic studies of hip fracture care provision and experiences will understand fracture service pathways. Conclusions:Greater understanding of current and expected fracture burdens, fracture risk factors, and existing fracture care provision, is intended to inform national clinical guidelines, health service policy and planning and future health service development in sub-Saharan Africa.
Which performance indicators are used globally for evaluating healthcare in patients with a hip fracture? : a mixed methods systematic review.
AIMS: Performance indicators are increasingly used to evaluate the quality of healthcare provided to patients with a hip fracture. The aim of this review was to map the variety of performance indicators used around the world and how they are defined. METHODS: We present a mixed methods systematic review of literature on the use of performance indicators in hip fracture care. Evidence was searched through 12 electronic databases and other sources. A Mixed Methods Appraisal Tool was used to assess methodological quality of studies meeting the inclusion criteria. A protocol for a suite of related systematic reviews was registered at PROSPERO (CRD42023417515). RESULTS: A total 24,634 articles were reviewed, of which 171 met the criteria of the review. Included studies were heterogenous in design and came from varied healthcare systems in 34 different countries. Most studies were conducted in high-income countries in Europe (n = 118), followed by North America (n = 33), Asia (n = 21), Australia (n = 10), and South America (n = 2). The highest number of studies in one country came from the UK (n = 45). Only seven of the 171 studies (< 2,000 participants) were conducted across ten low- and middle-income countries (LMICs). There was variation in the performance indicators reported from different healthcare systems, and indicators were often undefined or ambiguously defined. For example, there were multiple definitions of 'early' in terms of surgery, different or missing definitions of 'mobilization', and variety in what was included in an 'orthogeriatric assessment' in hip fracture care. However, several performance indicators appeared commonly, including time to surgery (n = 142/171; 83%), orthogeriatric review (n = 30; 17%), early mobilization after surgery (n = 58; 34%), and bone health assessment (n = 41; 24%). Qualitative studies (n = 18), mainly from high-income countries and India, provided evidence on the experiences of 192 patients and 138 healthcare professionals with regard to the use of performance indicators in clinical care and rehabilitation pathways. Themes included the importance of education and training in parallel with the introduction of performance indicators, clarity of roles with the clinical team, and the need for restructuring or integration of care pathways. CONCLUSION: This review identified a large number of performance indicators related to the delivery of healthcare for patients with a hip fracture. However, their definitions and thresholds varied across studies and countries. Evidence from LMICs is sparse. Both qualitative and quantitative evidence indicates that there remains a pressing need for further research into the use and standardization of performance indicators in hip fracture care and their influence on patient outcomes and economic costs.
Five-year outcomes for patients with a displaced fracture of the distal tibia.
AIMS: To report the outcomes of patients with a fracture of the distal tibia who were treated with intramedullary nail versus locking plate in the five years after participating in the Fixation of Distal Tibia fracture (FixDT) trial. METHODS: The FixDT trial reported the results for 321 patients randomized to nail or locking plate fixation in the first 12 months after their injury. In this follow-up study, we report the results of 170 of the original participants who agreed to be followed up until five years. Participants reported their Disability Rating Index (DRI) and health-related quality of life (EuroQol five-dimension three-level questionnaire) annually by self-reported questionnaire. Further surgical interventions related to the fracture were also recorded. RESULTS: There was no evidence of a difference in patient-reported disability, health-related quality of life, or the need for further surgery between participants treated with either type of fixation at five years. Considering the combined results for all participants, there was no significant change in DRI scores after the first 12 months of follow-up (difference between 12 and 24 months, 3.3 (95% confidence interval -1.8 to 8.5); p = 0.203), with patients reporting around 20% disability at five years. CONCLUSION: This study shows that the moderate levels of disability and reduced quality of life reported by participants 12 months after a fracture of the distal tibia persist in the medium term, with little evidence of improvement after the first year.
Shared imaging markers of fatigue across multiple sclerosis, aquaporin-4 antibody neuromyelitis optica spectrum disorder and MOG antibody disease.
Fatigue is frequently reported by patients with multiple sclerosis, aquaporin-4-antibody neuromyelitis optica spectrum disorder and myelin-oligodendrocyte-glycoprotein antibody disease; thus they could share a similar pathophysiological mechanism. In this cross-sectional cohort study, we assessed the association of fatigue with resting-state functional MRI, diffusion and structural imaging measures across these three disorders. Sixteen patients with multiple sclerosis, 17 with aquaporin-4-antibody neuromyelitis optica spectrum disorder and 17 with myelin-oligodendrocyte-glycoprotein antibody disease assessed, outside of relapses, at the Oxford Neuromyelitis Optica Service underwent Modified Fatigue Impact Scale, Hospital Anxiety and Depression Scale and Expanded Disability Status Scale scoring. A 3T brain and spinal cord MRI was used to derive cortical, deep grey and white matter volumetrics, lesions volume, fractional anisotropy, brain functional connectivity metrics, cervical spinal cord cross-sectional area, spinal cord magnetic transfer ratio and average functional connectivity between the ventral and the dorsal horns of the cervical cord. Linear relationships between MRI measures and total-, cognitive- and physical-fatigue scores were assessed. All analyses were adjusted for correlated clinical regressors. No significant differences in baseline clinical characteristics, fatigue, depression and anxiety questionnaires and disability measures were seen across the three diseases, except for older age in patients with aquaporin-4-antibody neuromyelitis optica spectrum disorder (P = 0.0005). In the total cohort, median total-fatigue score was 35.5 (range 3-72), and 42% of patients were clinically fatigued. A positive correlation existed between the total-fatigue score and functional connectivity of the executive/fronto-temporal network in the in left middle temporal gyrus (P = 0.033) and between the physical-fatigue score and functional connectivity of the sensory-motor network (P = 0.032) in both pre- and post-central gyri. A negative relationship was found between the total-fatigue score and functional connectivity of the salience network (P = 0.023) and of the left fronto-parietal network (P = 0.026) in the right supramarginal gyrus and left superior parietal lobe. No clear relationship between fatigue subscores and the average functional connectivity of the spinal cord was found. Cognitive-fatigue scores were positively associated with white matter lesion volume (P = 0.018) and negatively associated with white matter fractional anisotropy (P = 0.032). Structural, diffusion and functional connectivity alterations were not influenced by the disease group. Functional and structural imaging metrics associated with fatigue relate to brain rather than spinal cord abnormalities. Salience and sensory-motor networks alterations in relation to fatigue might indicate a disconnection between the perception of the interior body state and activity and the actual behavioural responses and performances (reversible or irreversible). Future research should focus on functional rehabilitative strategies.
A comparison of lesion mapping analyses based on CT versus MR imaging in stroke.
It is commonly asserted that MRI-derived lesion masks outperform CT-derived lesion masks in lesion-mapping analysis. However, no quantitative analysis has been conducted to support or refute this claim. This study reports an objective comparison of lesion-mapping analyses based on CT- and MRI-derived lesion masks to clarify how input imaging type may ultimately impact analysis results. Routine CT and MRI data were collected from 85 acute stroke survivors. These data were employed to create binarized lesion masks and conduct lesion-mapping analyses on simulated behavioral data. Following standard lesion-mapping analysis methodology, each voxel or region of interest (ROI) were considered as the underlying "target" within CT and MRI data independently. The resulting thresholded z-maps were compared between matched CT- and MRI-based analyses. Paired MRI- and CT-derived lesion masks were found to exhibit significant variance in location, overlap, and size. In ROI-level simulations, both CT and MRI-derived analyses yielded low Dice similarity coefficients, but CT analyses yielded a significantly higher proportion of results which overlapped with target ROIs. In single-voxel simulations, MRI-based lesion mapping was able to include more voxels than CT-based analyses, but CT-based analysis results were closer to the underlying target voxel. Simulated lesion-symptom mapping results yielded by paired CT and MRI lesion-symptom mapping analyses demonstrated moderate agreement in terms of Dice coefficient when systematic differences in cluster size and lesion overlay are considered. Overall, these results suggest that CT and MR-derived lesion-symptom mapping results do not reliably differ in accuracy. This finding is critically important as it suggests that future studies can employ CT-derived lesion masks if these scans are available within the appropriate time-window.
Acceptability and cultural appropriateness of a parenting programme to reduce violence against adolescents in Tanzania delivered at scale: Implications for scale-up.
Although parenting programmes may be effective at reducing violence against children (VAC), there is a limited understanding on how acceptable and appropriate such programmes are among parents/caregivers ('caregivers') when delivered at scale. This paper explores the acceptability and cultural appropriateness of a parenting programme for caregivers and their adolescent girls, Parenting for Lifelong Health for Teens (PLH-Teens), which was delivered at scale in rural and semi-urban Tanzania. This paper employed a qualitative research design involving 18 focus group discussions (FGDs) with caregivers (N = 120) and adolescent girls (N = 60). Participants reported that the programme was acceptable, culturally appropriate, and beneficial. The use of participatory approaches and in-person group sessions was appealing to caregivers. However, several challenges hindered consistent engagement. These factors ranged from initial community mistrust about the programme, social norms on parenting, and group interactions to individual-level participant factors, stigma, and feeling of shame for being selected to join a programme. Overall, PLH-Teens programme was perceived as addressing the real parenting needs of caregivers and their adolescents. There is a need to address the challenges families experienced as these could hinder the acceptability, sustainability, and continued scale up of PLH-Teens in future programme delivery.
A Digital Parenting Intervention With Intimate Partner Violence Prevention Content: Quantitative Pre-Post Pilot Study.
BACKGROUND: Intimate partner violence (IPV) and violence against children are global issues with severe consequences. Intersections shared by the 2 forms of violence have led to calls for joint programming efforts to prevent both IPV and violence against children. Parenting programs have been identified as a key entry point for addressing multiple forms of family violence. Building on the IPV prevention material that has been integrated into the parenting program ParentText, a digital parenting chatbot, this pilot study seeks to explore parents' engagement with the IPV prevention content in ParentText and explore preliminary changes in IPV. OBJECTIVE: This study aimed to assess parents' and caregivers' level of engagement with the IPV prevention material in the ParentText chatbot and explore preliminary changes in experiences and perpetration of IPV, attitudes toward IPV, and gender-equitable behaviors following the intervention. METHODS: Caregivers of children aged between 0 and 18 years were recruited through convenience sampling by research assistants in Cape Town, South Africa, and by UNICEF (United Nations Children's Fund) Jamaica staff in 3 parishes of Jamaica. Quantitative data from women in Jamaica (n=28) and South Africa (n=19) and men in South Africa (n=21) were collected electronically via weblinks sent to caregivers' phones using Open Data Kit. The primary outcome was IPV experience (women) and perpetration (men), with secondary outcomes including gender-equitable behaviors and attitudes toward IPV. Descriptive statistics were used to report sociodemographic characteristics and engagement outcomes. Chi-square tests and 2-tailed paired dependent-sample t tests were used to investigate potential changes in IPV outcomes between pretest and posttest. RESULTS: The average daily interaction rate with the program was 0.57 and 0.59 interactions per day for women and men in South Africa, and 0.21 for women in Jamaica. The rate of completion of at least 1 IPV prevention topic was 25% (5/20) for women and 5% (1/20) for men in South Africa, and 21% (6/28) for women in Jamaica. Exploratory analyses indicated significant pre-post reductions in overall IPV experience among women in South Africa (P=.01) and Jamaica (P=.01) and in men's overall harmful IPV attitudes (P=.01) and increases in men's overall gender-equitable behaviors (P=.02) in South Africa. CONCLUSIONS: To the best of our knowledge, this is the first pilot study to investigate user engagement with and indicative outcomes of a digital parenting intervention with integrated IPV prevention content. Study findings provide valuable insights into user interactions with the chatbot and shed light on challenges related to low levels of chatbot engagement. Indicative results suggest promising yet modest reductions in IPV and improvements in attitudes after the program. Further research using a randomized controlled trial is warranted to establish causality.
Using a Digital Parenting Intervention to Prevent Intimate Partner Violence and Promote Gender Equitable behaviors in South Africa and Jamaica: A Qualitative Study Exploring Partnered Parents' Experiences of ParentText.
This qualitative study explores caregivers' experiences of using a preprogramed, chatbot parenting intervention with integrated intimate partner violence (IPV) prevention content. The intervention aims to address the challenge of scale-up that in-person parenting programs often face while seeking to reduce both IPV and violence against children simultaneously. Conducted in South Africa and Jamaica, individual interviews and focus group discussions exploring the chatbot IPV prevention content were held with male and female caregivers. The thematic analysis revealed that caregivers perceived the chatbot to be accessible and observed positive changes in relationship dynamics, while also noting some technological barriers and limitations.
Parasitaemia and fever in uncomplicated Plasmodium vivax malaria: A systematic review and individual patient data meta-analysis.
BACKGROUND: Parasite density thresholds used for diagnosing symptomatic malaria are defined by the relationship between parasitaemia and fever. This relationship can inform the design and development of novel diagnostic tests but appropriate parasitaemia thresholds for Plasmodium vivax malaria remain poorly defined. METHODOLOGY/PRINCIPAL FINDINGS: We undertook an individual patient data meta-analysis of P. vivax clinical trials mapped to the WorldWide Antimalarial Resistance Network (WWARN) repository and used parasitaemia centiles of febrile patients at enrolment to derive proportions of patients who would have been diagnosed at different parasite densities. Febrile and afebrile patients with recurrent infections were selected to estimate pyrogenic densities using receiver operating characteristic curve analysis. In total 13,263 patients from 50 studies were included in the analysis. In 27 studies (8,378 febrile patients) in which a parasitaemia threshold was not applied as an inclusion criterion, the median parasitaemia at enrolment was 3,280/µL (interquartile range, 968 - 8,320); 90% of patients had a parasitaemia above 278/µL (10th centile), and 95% above 120/µL (5th centile). The 10th centile was higher in children <5 years old (368/µL) compared to adults ≥15 years (240/µL). In high relapse periodicity regions (Southeast Asia and Oceania) febrile patients presented with lower parasitaemias (10th centile 185/µL vs. 504/µL) and a wider range of parasitaemias compared to those from low relapse periodicity regions (interquartile range 760/µL - 8,774/µL vs. 1,204/µL - 8,000/µL). In total 2,270 patients from 41 studies had at least one episode of recurrent P. vivax parasitaemia, of whom 43% (849/1,983) were febrile at their first recurrence. The P. vivax pyrogenic density at first recurrence was 1,063/µL, defining fever with 74% sensitivity and 65% specificity. The pyrogenic density was lower in young children compared to adults ≥15 years (935/µL vs. 1,179/µL). CONCLUSIONS/SIGNIFICANCE: The derived parasitaemia centiles will inform the use of current and the design of novel point-of-care tests to diagnose patients with symptomatic vivax malaria. Variation by age and location should be considered when selecting diagnostic thresholds and interpreting results. TRIAL REGISTRATION: This trial was registered with PROSPERO: CRD42021254905. The date of the first registration was 17th May 2021.
Performance of quantitative point-of-care tests to measure G6PD activity: An individual participant data meta-analysis.
BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the main risk factor for severe haemolysis following treatment with 8-aminoquinolines (8AQ). The World Health Organization recommends G6PD testing prior to 8AQ-based hypnozoitocidal treatment. METHODS: We undertook an individual level meta-analysis of the performance of commercially available quantitative point-of-care diagnostics (PoCs) compared with reference spectrophotometry. A systematic literature search (PROSPERO: CRD42022330733) identified 595 articles of which 16 (2.7%) fulfilled pre-defined inclusion criteria and were included in the analysis, plus an additional 4 datasets. In total there were 12,678 paired measurements analyzed, 10,446 (82.4%) by STANDARD G6PD Test (SD Biosensor, RoK, [SDB]), 2,042 (16.1%) by CareStart G6PD Biosensor (AccessBio, USA, [CSA]), 150 (1.2%) by CareStart Biosensor (WellsBio, RoK [CSW]), and 40 (0.3%) by FINDER (Baebies, USA, [FBA]). FINDINGS: The pooled sensitivities of the SDB when measuring G6PD activity <30% of normal were 0.82 (95% confidence interval [CI]: 0.72-0.89) for capillary and 0.93 (95% CI: 0.75-0.99) for venous blood samples. The corresponding values for measuring <70% G6PD activity were 0.93 (95% CI: 0.67-0.99) and 0.89 (95% CI: 0.73-0.96), respectively. The pooled specificity of the SDB was high (>96%) for all blood samples and G6PD activity thresholds. Irrespective of the blood samples and thresholds applied, sensitivity of the CSA did not exceed 62%, although specificity remained high at both 30% and 70% thresholds (>88%). Only one study each for CSW and FBA was included. Sensitivities of the CSW were 0.04 (95% CI: 0.01-0.14) and 0.81 (95% CI: 0.71-0.89) at the 30% and 70% thresholds, respectively (venous blood samples). Sensitivities of the FBA were 1.00 (95% CI: 0.29-1.00) and 0.75 (95% CI: 0.19-0.99) at the 30% and 70% thresholds (venous blood samples). Specificities of the CSW and FBA were consistently high (>90%) at both thresholds. Accuracy of the SDB was higher in females at the 30% cut-off (OR: 3.49, p=0.002) and lower in malaria patients at the 70% cut-off (OR: 0.59, p = 0.005). CONCLUSIONS: The SDB performed better than other PoCs. More evidence was available for the performance of the SDB compared to other PoCs, giving higher confidence in its utility in diagnosing G6PD deficiency.
Evaluation of the diagnostic accuracy of Xpert® Mpox and STANDARD™ M10 MPX/OPX for the detection of monkeypox virus.
OBJECTIVES: Evaluation of diagnostic accuracy of two point-of-care (POC) molecular diagnostic tests for the detection of monkeypox virus (MPXV): Xpert® Mpox (Cepheid, Inc., USA) and STANDARD™ M10 MPX/OPX (SD Biosensor, Inc., Korea). METHODS: Diagnostic accuracy of both POC platforms was evaluated using 53 upper-respiratory swabs (URS) and 32 skin lesions swabs (SS) collected from mpox and COVID-19 patients in the UK against the Sansure (Sansure Biotech Inc.) and CDC reference qPCR tests. The analytical sensitivity of both platforms was assessed using a viral isolate from II, B.1 lineage. RESULTS: The overall sensitivity and specificity of the Xpert® Mpox was 97.67% [95% CI 87.71-99.94%] and 88.57% [95% CI 73.26-96.80%] and 97.44% [95% CI 86.52-99.94%] and 74.42% [95% CI 58.83-86.48%] comparing the Sansure and CDC qPCR, respectively and for the M10 MPX/OPX was 87.80% [95% CI 73.80-95.92%] and 76.60% [95% CI 61.97-87.70%] and 94.29% [95% CI 80.84-99.30%] and 86.67% [95% CI 73.21-94.95%] with the Sansure and CDC qPCR. CONCLUSION: The Xpert® Mpox had good diagnostic accuracy for both sample types while the M10 MPX/OPX clinical accuracy was deficient with URS. Our data supports the use of URS during the first 3 days of symptoms onset for mpox diagnosis.
Embedding treatment in stronger care systems.
A key lesson from the west Africa (2014-16) Ebola disease epidemic was that outbreak responses fail when they respond to patients through a narrow clinical lens without considering the broader community and social context of care. Here, in the second of two Series papers on the modern landscape of Ebola disease, we review progress made in the last decade to improve patient-centred care. Although the biosafety imperatives of treating Ebola disease remain, recent advances show how to mitigate these so that patients are cared for in a safe and dignified manner that encourages early treatment-seeking behaviour and provides support after the return of patients to their communities. We review advances in diagnostics, including faster Ebola disease detection via real-time RT-PCR, and consider design improvements in Ebola disease treatment units that enhance patient safety and dignity. We also review advances in care provision, such as the integration of palliative care and mobile communication into routine care, and address how greater access to research is possible through harmonised clinical trials. Finally, we discuss how strengthened community engagement and psychosocial programmes are addressing stigma and providing holistic support for survivors.
Situational analysis of antibiotic prescriptions in Kenyan neonatal units for antimicrobial stewardship: a retrospective longitudinal study.
BACKGROUND: High antibiotic use in neonatal units may drive antimicrobial resistance and cause harm including mortality. We used data from 22 Kenyan neonatal units to (1) describe the proportion with antibiotic prescriptions at admission; (2) assess the predictors of non-first line antibiotic prescription; (3) estimate antibiotic use, and (4) explore postadmission antibiotic switching. METHODS: Retrospective longitudinal study from 1st September 2020 to 31st October 2023. Antibiotics were classified as first line (penicillin plus gentamicin only), third generation cephalosporins (ceftazidime or ceftriaxone) or others. The proportion of antibiotic prescriptions were computed, and a multilevel logistic regression model used to analyse predictors of non-first line prescription. Antibiotic use was quantified by days of therapy (DOT) and length of therapy (LOT). FINDINGS: Most neonates-62.6% (51,883/82,834)- received at least one antibiotic prescription at admission. Overall, first line antibiotics constituted 86% (44,636/51,883) but third generation cephalosporin use reached 100% in two facilities temporarily. The odds of non-first line prescription was greatest for outborn neonates (Odds ratio 2.27, 95% CI 2.12-2.43) while the estimated antibiotic consumption was 418 (389-500) per 1000 patient days by LOT and 744 (691-869) by DOT. From exploratory data post admission switching was most commonly to third generation cephalosporins. INTERPRETATION: There is a high use of antibiotics potentially related to severity of illness at admission. Adherence to national guidelines for first line antibiotics is however generally high. Estimation of neonatal antibiotic prescription patterns and use over time and place is feasible and will be important in assessing the effectiveness of antimicrobial stewardship in Kenya and elsewhere in reducing antimicrobial resistance. FUNDING: This work was funded by the Wellcome Trust.
Why the growth of arboviral diseases necessitates a new generation of global risk maps and future projections.
Global risk maps are an important tool for assessing the global threat of mosquito and tick-transmitted arboviral diseases. Public health officials increasingly rely on risk maps to understand the drivers of transmission, forecast spread, identify gaps in surveillance, estimate disease burden, and target and evaluate the impact of interventions. Here, we describe how current approaches to mapping arboviral diseases have become unnecessarily siloed, ignoring the strengths and weaknesses of different data types and methods. This places limits on data and model output comparability, uncertainty estimation and generalisation that limit the answers they can provide to some of the most pressing questions in arbovirus control. We argue for a new generation of risk mapping models that jointly infer risk from multiple data types. We outline how this can be achieved conceptually and show how this new framework creates opportunities to better integrate epidemiological understanding and uncertainty quantification. We advocate for more co-development of risk maps among modellers and end-users to better enable risk maps to inform public health decisions. Prospective validation of risk maps for specific applications can inform further targeted data collection and subsequent model refinement in an iterative manner. If the expanding use of arbovirus risk maps for control is to continue, methods must develop and adapt to changing questions, interventions and data availability.
Anakinra for dengue patients with hyperinflammation: protocol for a randomized double-blind placebo-controlled trial.
BACKGROUND: Novel host-directed therapies are urgently needed for patients with dengue, particularly those at high risk of developing severe disease. Broad immunosuppression using corticosteroids in unselected patients with dengue has so far been unsuccessful. Patients with hyperinflammation (raised CRP and/or ferritin levels) are at highest risk of poor outcomes in dengue. Anakinra is a licensed, bio-engineered form of the naturally occurring IL-1R antagonist which has shown efficacy in other acute viral-associated hyperinflammatory syndromes. METHODS: This is a randomized placebo-controlled phase II trial of anakinra in 160 patients ≥ 12 years old, diagnosed as having dengue with warning signs or severe dengue and the hyperinflammatory syndrome (plasma ferritin >2000 ng/ml). Participants will receive a 4-day course of either anakinra or placebo. The primary endpoint is the efficacy of anakinra measured by the delta mSOFA score* (change in mSOFA score over 4 days after randomization). The accompanying immunological and transcriptomic analyses aim to identify novel mechanisms and pathways that may represent future biomarkers and therapeutic targets. DISCUSSION: The observed immunomodulatory benefit of anakinra in acute viral-associated hyperinflammatory syndromes including COVID-19 and auto-immune diseases makes this medication a promising potential treatment for dengue patients with hyperinflammation. This trial will assess the safety and efficacy of anakinra in patients with severe dengue or at high risk of developing life-threatening dengue disease. REGISTRATION: ClinicalTrials.gov (NCT05611710).