A randomised Trial of Autologous Blood products, leukocyte and platelet-rich fibrin (L-PRF), to promote ulcer healing in LEprosy: The TABLE trial.

INTRODUCTION: Autologous blood products like Platelet Rich Plasma (PRP) and Leukocyte and Platelets Rich Fibrin (L-PRF) have been used for many years across many types of skin ulcers. However, the effectiveness of autologous blood products on wound healing is not well established. METHODS: We evaluated the 'second generation' autologous product- Leukocyte and Platelet- Rich Fibrin (L-PRF). Our trial was undertaken on patients suffering from neuropathic leprosy ulcers at the Anandaban hospital which serves the entire country of Nepal. We conducted a 1:1 (n = 130) individually randomised trial of L-PRF (intervention) vs. normal saline dressing (control) to compare rate of healing and time to complete healing. Rate of healing was estimated using blind assessments of ulcer areas based on three different measurement methods. Time to complete healing was measured by the local unblinded clinicians and by blind assessment of ulcer images. RESULTS: The point estimates for both outcomes were favourable to L-PRF but the effect sizes were small. Unadjusted mean differences (intervention vs control) in mean daily healing rates (cm2) were respectively 0.012 (95% confidence interval 0.001 to 0.023, p = 0.027); 0.016 (0.004 to 0.027, p = 0.008) and 0.005 (-0.005 to 0.016, p = 0.313) across the three measurement methods. Time to complete healing at 42 days yielded Hazard Ratios (unadjusted) of 1.3 (0.8 to 2.1, p = 0.300) assessed by unblinded local clinicians and 1.2 (0.7 to 2.0, p = 0.462) on blind assessment. CONCLUSION: Any benefit from L-PRF appears insufficient to justify routine use in care of neuropathic ulcers in leprosy. TRIAL REGISTRATION: ISRCTN14933421. Date of trial registration: 16 June 2020.

Autologous blood products: Leucocyte and Platelets Rich Fibrin (L-PRF) and Platelets Rich Plasma (PRP) gel to promote cutaneous ulcer healing - a systematic review.

OBJECTIVE: To summarise evidence on the effectiveness of Platelet-Rich Plasma (PRP) gel and Leucocyte and Platelet Rich Fibrin (L-PRF) gel as agents promoting ulcer healing compared with the standard wound dressing techniques alone. DESIGN: Systematic review. ELIGIBILITY CRITERIA: Individual patient randomised controlled trials on skin ulcers of all types excluding traumatic lesions.Intervention group: treatment with topical application of L-PRF gel or PRP gel to the wound surface. CONTROL GROUP: treatment with standard skin ulcer care using normal saline, normgel or hydrogel dressings. INFORMATION SOURCES: Medline (Ovid), Excerpta Medica Database (EMBASE), Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science and manual search of studies from previous systematic reviews and meta-analyses. The papers published from 1946 to 2022 with no restriction on geography and language were included. The last date of the search was performed on 29 August 2022. DATA EXTRACTION AND SYNTHESIS: Independent reviewers identified eligible studies, extracted data, assessed risk of bias using V.2 of the Cochrane risk-of-bias tool for randomised trials tool and assessed certainty of evidence by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. MAIN OUTCOME MEASURES: Time to complete healing, proportion healed at a given time and rate of healing. RESULTS: Seven studies met the inclusion criteria, five using PRP gel and two using L-PRF gel. One study showed a better proportion of complete healing, three reported reduced meantime to complete healing and five showed improved rate of healing per unit of time in the intervention group. The risk of bias was high across all studies with one exception and the GRADE showed very low certainty of evidence. CONCLUSION: The findings show potential for better outcomes in the intervention; however, the evidence remains inconclusive highlighting a large research gap in ulcer treatment and warrant better-designed clinical trials. PROSPERO REGISTRATION NUMBER: CRD42022352418.

Prevalence of plantar ulcer and its risk factors in leprosy: a systematic review and meta-analysis.

BACKGROUND: Plantar ulcers are a leading complication of leprosy that requires frequent visits to hospital and is associated with stigma. The extent of burden of ulcers in leprosy and its risk factors are scant impeding the development of targeted interventions to prevent and promote healing of ulcers. The aim of this review is to generate evidence on the prevalence of plantar ulcer and its risk factors in leprosy. METHODS: Databases (Medline, Embase, Web of Science, CINAHL, BVS), conference abstracts and reference lists were searched for eligible studies. Studies were included that reported a point prevalence of plantar ulcer and/or its "risk factors" associated with development of ulcers (either causatively or predictively), including individual level, disease related and bio-mechanical factors. We followed PRISMA guidelines for this review. Random-effects meta-analysis was undertaken to estimate the pooled point prevalence of ulcers. Reported risk factors in included studies were narratively synthesised. This review is registered in PROSPERO: CRD42022316726. RESULTS: Overall, 15 studies (8 for prevalence of ulcer and 7 for risk factors) met the inclusion criteria. The pooled point prevalence of ulcer was 34% (95% CIs: 21%, 46%) and 7% (95% CIs: 4%, 11%) among those with foot anaesthesia and among all people affected by leprosy, respectively. Risk factors for developing ulcers included: unable to feel 10 g of monofilament on sensory testing, pronated/hyper-pronated foot, foot with peak plantar pressure, foot with severe deformities, and those with lower education and the unemployed. CONCLUSIONS: The prevalence of plantar ulceration in leprosy is as high as 34% among those with loss of sensation in the feet. However, the incidence and recurrence rates of ulceration are least reported. The inability to feel 10 g of monofilament appears to be a strong predictor of those at risk of developing ulcers. However, there is a paucity of evidence on identifying those at risk of developing plantar ulcers in leprosy. Prospective studies are needed to estimate the incidence of ulcers. Identifying individuals at risk of ulcers will help design targeted interventions to minimize risk factors, prevent ulcers and promote ulcer healing.

Safety and upscaling of remote consulting for long-term conditions in primary health care in Nigeria and Tanzania (REaCH trials): stepped-wedge trials of training, mobile data allowance, and implementation.

BACKGROUND: In-person health care poses risks to health workers and patients during pandemics. Remote consultations can mitigate these risks. The REaCH intervention comprised training and mobile data allowance provision for mobile phones to support remotely delivered primary care in Africa compared with no training and mobile data allowance. The aim of this study was to estimate the effects of REaCH among adults with non-communicable diseases on remote and face-to-face consultation rates, patient safety, and trustworthiness of consultations. METHODS: In these two independent stepped-wedge cluster randomised controlled trials, we enrolled 20 primary care clusters in each of two settings (Oyo State, Nigeria, and Morogoro Region, Tanzania). Eligible clusters had 100 or more patients with diabetes, hypertension, and cardiovascular or pulmonary disease employing five health workers. Clusters were computer-randomised to one of ten (Nigeria) or one of seven (Tanzania) sequences to receive the REaCH intervention. Only outcome assessors were masked. Primary outcomes were consultation, prescription, and investigation rates, and trustworthiness collected monthly for 12 months (Nigeria) and 9 months (Tanzania) from open cohorts. Ten randomly sampled consulting patients per cluster-month completed patient reported outcome measures. This trial was registered with ISRCTN, ISRCTN17941313. FINDINGS: Overall, 40 clusters comprising 8776 (Nigeria) and 3246 (Tanzania) patients' open cohort data were analysed (6377 [72·7%] of 8776 females in Nigeria, and 2235 [68·9%] of 3246 females in Tanzania). The mean age of the participants was 55·3 years (SD 13·9) in Nigeria and 59·2 years (14·2) in Tanzania. In Nigeria, no evidence of change in face-to-face consulting rate was observed (rate ratio [RR] 1·06, 95% CI 0·98 to 1·09; p=0·16); however, remote consultations increased four-fold (4·44, 1·34 to >10; p=0·01). In Tanzania, face-to-face (0·94, 0·61 to 1·67; p=0·99) and remote consulting rates (1·17, 0·56 to 5·57; p=0·39) were unchanged. There was no evidence of difference in prescribing rates (Nigeria: 1·05, 0·60 to 1·14; p=0·23; Tanzania: 0·92, 0·60 to 1·67; p=0·97), investigation rates (Nigeria: 1·06, 0·23 to 2·12; p=0·49; Tanzania: 1·15, 0·35 to 1·64; 0·58) or trustworthiness scores (Nigeria: mean difference 0·05, 95% CI -0·45 to 0·42; p=0·89; Tanzania: 0·07, -0·15 to 0·76; p=0·70). INTERPRETATION: REaCH can be implemented and could improve intervention versus control health-care access. Remote consultations appear safe and trustworthy, supporting universal health coverage. FUNDING: The UK Research and Innovation Collective Fund. TRANSLATIONS: For the Swahili and Yoruba translations of the abstract see Supplementary Materials section.

Optimal study designs for cluster randomised trials: An overview of methods and results.

There are multiple possible cluster randomised trial designs that vary in when the clusters cross between control and intervention states, when observations are made within clusters, and how many observations are made at each time point. Identifying the most efficient study design is complex though, owing to the correlation between observations within clusters and over time. In this article, we present a review of statistical and computational methods for identifying optimal cluster randomised trial designs. We also adapt methods from the experimental design literature for experimental designs with correlated observations to the cluster trial context. We identify three broad classes of methods: using exact formulae for the treatment effect estimator variance for specific models to derive algorithms or weights for cluster sequences; generalised methods for estimating weights for experimental units; and, combinatorial optimisation algorithms to select an optimal subset of experimental units. We also discuss methods for rounding experimental weights, extensions to non-Gaussian models, and robust optimality. We present results from multiple cluster trial examples that compare the different methods, including determination of the optimal allocation of clusters across a set of cluster sequences and selecting the optimal number of single observations to make in each cluster-period for both Gaussian and non-Gaussian models, and including exchangeable and exponential decay covariance structures.

Evaluation of combinatorial optimisation algorithms for c-optimal experimental designs with correlated observations.

We show how combinatorial optimisation algorithms can be applied to the problem of identifying c-optimal experimental designs when there may be correlation between and within experimental units and evaluate the performance of relevant algorithms. We assume the data generating process is a generalised linear mixed model and show that the c-optimal design criterion is a monotone supermodular function amenable to a set of simple minimisation algorithms. We evaluate the performance of three relevant algorithms: the local search, the greedy search, and the reverse greedy search. We show that the local and reverse greedy searches provide comparable performance with the worst design outputs having variance <10% greater than the best design, across a range of covariance structures. We show that these algorithms perform as well or better than multiplicative methods that generate weights to place on experimental units. We extend these algorithms to identifying modle-robust c-optimal designs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11222-023-10280-w.

Evaluation of an organisational-level monetary incentive to promote the health and wellbeing of workers in small and medium-sized enterprises: A mixed-methods cluster randomised controlled trial.

We conducted an independent evaluation on the effectiveness of an organisational-level monetary incentive to encourage small and medium-sized enterprises (SMEs) to improve employees' health and wellbeing. This was A mixed-methods cluster randomised trial with four arms: high monetary incentive, low monetary incentive, and two no monetary incentive controls (with or without baseline measurements to examine 'reactivity' The consequence of particpant awareness of being studied, and potential impact on participant behavior effects). SMEs with 10-250 staff based in West Midlands, England were eligible. We randomly selected up to 15 employees at baseline and 11 months post-intervention. We elicited employee perceptions of employers' actions to improve health and wellbeing; and employees' self-reported health behaviours and wellbeing. We also interviewed employers and obtained qualitative data. One hundred and fifty-two SMEs were recruited. Baseline assessments were conducted in 85 SMEs in three arms, and endline assessments in 100 SMEs across all four arms. The percentage of employees perceiving "positive action" by their employer increased after intervention (5 percentage points, pp [95% Credible Interval -3, 21] and 3pp [-9, 17], in models for high and low incentive groups). Across six secondary questions about specific issues the results were strongly and consistently positive, especially for the high incentive. This was consistent with qualitative data and quantitative employer interviews. However, there was no evidence of any impact on employee health behaviour or wellbeing outcomes, nor evidence of 'reactivity'. An organisational intervention (a monetary incentive) changed employee perceptions of employer behaviour but did not translate into changes in employees' self-reports of their own health behaviours or wellbeing. Trial registration: AEARCTR-0003420, registration date: 17.10.2018, retrospectively registered (delays in contracts and identfying a suitable trial registry). The authors confirm that there are no ongoing and related trials for this intervention.

Permutation-based multiple testing corrections for P $$ P $$ -values and confidence intervals for cluster randomized trials.

In this article, we derive and compare methods to derive P-values and sets of confidence intervals with strong control of the family-wise error rates and coverage for estimates of treatment effects in cluster randomized trials with multiple outcomes. There are few methods for P-value corrections and deriving confidence intervals, limiting their application in this setting. We discuss the methods of Bonferroni, Holm, and Romano and Wolf and adapt them to cluster randomized trial inference using permutation-based methods with different test statistics. We develop a novel search procedure for confidence set limits using permutation tests to produce a set of confidence intervals under each method of correction. We conduct a simulation-based study to compare family-wise error rates, coverage of confidence sets, and the efficiency of each procedure in comparison to no correction using both model-based standard errors and permutation tests. We show that the Romano-Wolf type procedure has nominal error rates and coverage under non-independent correlation structures and is more efficient than the other methods in a simulation-based study. We also compare results from the analysis of a real-world trial.

Protocol for a parallel group, two-arm, superiority cluster randomised trial to evaluate a community-level complementary-food safety and hygiene and nutrition intervention in Mali: the MaaCiwara study (version 1.3; 10 November 2022).

BACKGROUND: Diarrhoeal disease remains a significant cause of morbidity and mortality among the under-fives in many low- and middle-income countries. Changes to food safety practices and feeding methods around the weaning period, alongside improved nutrition, may significantly reduce the risk of disease and improve development for infants. We describe a protocol for a cluster randomised trial to evaluate the effectiveness of a multi-faceted community-based educational intervention that aims to improve food safety and hygiene behaviours and enhance child nutrition. METHODS: We describe a mixed-methods, parallel group, two-arm, superiority cluster randomised controlled trial with baseline measures. One hundred twenty clusters comprising small urban and rural communities will be recruited in equal numbers and randomly allocated in a 1:1 ratio to either treatment or control arms. The community intervention will be focussed around an ideal mother concept involving all community members during campaign days with dramatic arts and pledging, and follow-up home visits. Participants will be mother-child dyads (27 per cluster period) with children aged 6 to 36 months. Data collection will comprise a day of observation and interviews with each participating mother-child pair and will take place at baseline and 4 and 15 months post-intervention. The primary analysis will estimate the effectiveness of the intervention on changes to complementary-food safety and preparation behaviours, food and water contamination, and diarrhoea. Secondary outcomes include maternal autonomy, enteric infection, nutrition, child anthropometry, and development scores. A additional structural equation analysis will be conducted to examine the causal relationships between the different outcomes. Qualitative and health economic analyses including process evaluation will be done. CONCLUSIONS: The trial will provide evidence on the effectiveness of community-based behavioural change interventions designed to reduce the burden of diarrhoeal disease in the under-fives and how effectiveness varies across different contexts. TRIAL REGISTRATION: ISRCTN14390796. Registration date December 13, 2021.

Evaluations of water, sanitation and hygiene interventions should not use diarrhoea as (primary) outcome.

Water, sanitation and hygiene interventions have been the subject of cluster trials of unprecedented size, scale and cost in recent years. However, the question 'what works in water, sanitation, hygiene (WASH)?' remains poorly understood. Evaluations of community interventions to prevent infectious disease typically use lab-confirmed infection as a primary outcome; however, WASH trials mostly use reported diarrhoea. While diarrhoea is a significant source of morbidity, it is subjected to significant misclassification error with respect to enteric infection due to the existence of non-infectious diarrhoea and asymptomatic infection. We show how this may lead to bias of estimated effects of interventions from WASH trials towards no effect. The problem is further compounded by other biases in the measurement process. Alongside testing for infection of the gut, an examination of the causal assumptions underlying WASH interventions present several other reliable alternative and complementary measurements and outcomes. Contemporary guidance on the evaluation of complex interventions requires researchers to take a broad view of the causal effects of an intervention across a system. Reported diarrhoea can fail to even be a reliable measure of changes to gastrointestinal health and so should not be used as a primary outcome if we are to progress our knowledge of what works in WASH.

Prevalence and determinants of oral health conditions and treatment needs among slum and non-slum urban residents: Evidence from Nigeria.

Oral diseases constitute a neglected epidemic in Low and Middle-Income Countries (LMICs). An understanding of its distribution and severity in different settings can aid the planning of preventive and therapeutic services. This study assessed the oral health conditions, risk factors, and treatment needs among adult residents in the slum and compared findings with non-slum urban residents in Ibadan, Nigeria. The Multistage sampling was used to select adult (≥18-years) residents from a slum and a non-slum urban sites. Information sought from participants included dietary habits, oral hygiene practices, and the use of dental services. Oral examinations were performed in line with WHO guidelines. Associations were examined using logistic regression. Mediation analysis was undertaken using generalized structural equation modeling. The sample comprised 678 slum and 679 non-slum residents. Median age in slum vs non-slum was 45 (IQR:32-50) versus 38 (IQR:29-50) years. Male: female ratio was 1:2 in both sites. Prevalence of oral diseases (slum vs non-slum sites): dental caries (27% vs 23%), gingival bleeding (75% vs 53%) and periodontal pocket (23% vs 16%). The odds of having dental caries were 21% higher for the slum dwellers compared to non-slum residents (OR = 1.21, 95% CI:0.94 to 1.56); and 50% higher for periodontal pocket (OR = 1.50, 95%CI: 1.13 to 1.98), after adjusting for age and sex. There was little evidence that tooth cleaning frequency mediated the relationship between place of residence and caries (OR = 0.95, 95%CI: 0.87 to 1.03 [indirect effect], 38% mediated) or periodontal pocket (OR = 0.95, 95%CI: 0.86 to 1.04, 15% mediated). Thirty-five percent and 27% of residents in the slum and non-slum sites respectively required the "prompt and urgent" levels of treatment need. Oral diseases prevalence in both settings are high and the prevalence was generally higher in the slum with correspondingly higher levels of prompt and urgent treatment needs. Participants may benefit from targeted therapeutic and health promotion intervention services.

Examining organisational responses to performance-based financial incentive systems: a case study using NHS staff influenza vaccination rates from 2012/2013 to 2019/2020.

OBJECTIVE: Financial incentives are often applied to motivate desirable performance across organisations in healthcare systems. In the 2016/2017 financial year, the National Health Service (NHS) in England set a national performance-based incentive to increase uptake of the influenza vaccination among frontline staff. Since then, the threshold levels needed for hospital trusts to achieve the incentive (ie, the targets) have ranged from 70% to 80%. The present study examines the impact of this financial incentive across eight vaccination seasons. DESIGN: A retrospective observational study examining routinely recorded rates of influenza vaccination among staff in all acute NHS hospital trusts across eight vaccination seasons (2012/2013-2019/2020). The number of trusts included varied per year, from 127 to 137, due to organisational changes. McCrary's density test is conducted to determine if the number of hospital trusts narrowly achieving the target by the end of each season is higher than would be expected in the absence of any responsiveness to the target. We refer to this bunching above the target threshold as a 'threshold effect'. RESULTS: In the years before a national incentive was set, 9%-31% of NHS Trusts reported achieving the target, compared with 43%-74% in the 4 years after. Threshold effects did not emerge before the national incentive for payment was set; however, since then, threshold effects have appeared every year. Some trusts report narrowly achieving the target each year, both as the target rises and falls. Threshold effects were not apparent at targets for partial payments. CONCLUSIONS: We provide compelling evidence that performance-based financial incentives produced threshold effects. Policymakers who set such incentives are encouraged to track threshold effects since they contain information on how organisations are responding to an incentive, what enquiries they may wish to make, how the incentive may be improved and what unintended effects it may be having.

Outcomes for surgical procedures funded by the English health service but carried out in public versus independent hospitals: a database study.

BACKGROUND: The outcomes of elective surgery in public versus Independent Sector Healthcare Providers (ISHPs) are a matter of policy relevance and theoretical interest. METHODS: Retrospective study of all National Health Service (NHS) hospitals and ISHPs in England that provided NHS-funded elective surgery. We used data from the England-wide Hospital Episode Statistics to study 18 common surgical procedures performed between 2006 and 2019. In-hospital outcomes included length of stay, emergency transfers to another hospital or death. Posthospital outcomes included readmission or death within 28 days. Outcomes were compared for each operation type by propensity score matching and survival analysis. RESULTS: The data set included 3 203 331 operations in 734 NHS hospitals and 468 259 operations in 274 ISHPs.In-hospital outcomes: Across all 18 included operation types, length of stay was significantly longer for patients treated in NHS hospitals compared with ISHPs. Effect sizes ranged from a hazard ratio (HR) of 2.15 (95% CI 1.72 to 2.68) for total hip replacement to 1.07 (95% CI 1.05 to 1.09) for wisdom tooth removal; a mean difference of 2.49 and 0.02 days, respectively.Postdischarge outcomes: Treatment at an ISHP was associated with a lower risk of emergency readmission compared with NHS treatment. HRs ranged from 0.36 (95% CI 0.28 to 0.46) for lumbar decompression to 0.75 (95% CI 0.67 to 0.85) for cholecystectomy; absolute risk differences of 1.5 and 1.3 percentage points. There was no difference in mortality. CONCLUSION: Elective surgery in an ISHP is associated with shorter lengths of stay and lower readmission rates than treatment in NHS hospitals across 18 operation types. The data were matched on observable covariates, but we cannot exclude selection bias due to unobserved confounders.

Spatiotemporal analysis of the first wave of COVID-19 hospitalisations in Birmingham, UK.

OBJECTIVES: To evaluate the spatiotemporal distribution of the incidence of COVID-19 hospitalisations in Birmingham, UK during the first wave of the pandemic to support the design of public health disease control policies. DESIGN: A geospatial statistical model was estimated as part of a real-time disease surveillance system to predict local daily incidence of COVID-19. PARTICIPANTS: All hospitalisations for COVID-19 to University Hospitals Birmingham NHS Foundation Trust between 1 February 2020 and 30 September 2020. OUTCOME MEASURES: Predictions of the incidence and cumulative incidence of COVID-19 hospitalisations in local areas, its weekly change and identification of predictive covariates. RESULTS: Peak hospitalisations occurred in the first and second weeks of April 2020 with significant variation in incidence and incidence rate ratios across the city. Population age, ethnicity and socioeconomic deprivation were strong predictors of local incidence. Hospitalisations demonstrated strong day of the week effects with fewer hospitalisations (10%-20% less) at the weekend. There was low temporal correlation in unexplained variance. By day 50 at the end of the first lockdown period, the top 2.5% of small areas had experienced five times as many cases per 10 000 population as the bottom 2.5%. CONCLUSIONS: Local demographic factors were strong predictors of relative levels of incidence and can be used to target local areas for disease control measures. The real-time disease surveillance system provides a useful complement to other surveillance approaches by producing real-time, quantitative and probabilistic summaries of key outcomes at fine spatial resolution to inform disease control programmes.

A household-based community health worker programme for non-communicable disease, malnutrition, tuberculosis, HIV and maternal health: a stepped-wedge cluster randomised controlled trial in Neno District, Malawi.

BACKGROUND: Community health worker (CHW) programmes are a valuable component of primary care in resource-poor settings. The evidence supporting their effectiveness generally shows improvements in disease-specific outcomes relative to the absence of a CHW programme. In this study, we evaluated expanding an existing HIV and tuberculosis (TB) disease-specific CHW programme into a polyvalent, household-based model that subsequently included non-communicable diseases (NCDs), malnutrition and TB screening, as well as family planning and antenatal care (ANC). METHODS: We conducted a stepped-wedge cluster randomised controlled trial in Neno District, Malawi. Six clusters of approximately 20 000 residents were formed from the catchment areas of 11 healthcare facilities. The intervention roll-out was staggered every 3 months over 18 months, with CHWs receiving a 5-day foundational training for their new tasks and assigned 20-40 households for monthly (or more frequent) visits. FINDINGS: The intervention resulted in a decrease of approximately 20% in the rate of patients defaulting from chronic NCD care each month (-0.8 percentage points (pp) (95% credible interval: -2.5 to 0.5)) while maintaining the already low default rates for HIV patients (0.0 pp, 95% CI: -0.6 to 0.5). First trimester ANC attendance increased by approximately 30% (6.5pp (-0.3, 15.8)) and paediatric malnutrition case finding declined by 10% (-0.6 per 1000 (95% CI -2.5 to 0.8)). There were no changes in TB programme outcomes, potentially due to data challenges. INTERPRETATION: CHW programmes can be successfully expanded to more comprehensively address health needs in a population, although programmes should be carefully tailored to CHW and health system capacity.

An individual randomised efficacy trial of autologous blood products, leukocyte and platelet-rich fibrin (L-PRF), to promote ulcer healing in leprosy in Nepal: the TABLE trial protocol.

BACKGROUND: Leprosy is curable with multidrug therapy and treatment in the early stages can prevent disability. However, local nerve damage can lead to injury and consequently recurring and disfiguring ulcers. The aim of this study is to evaluate the treatment of leprosy ulcers using an autologous blood product; leukocyte and platelet-rich fibrin (L-PRF) to promote healing. METHODS: This is a single-centre study in the Anandaban Hospital, The Leprosy Mission Nepal, Kathmandu, Nepal. Consenting patients (n=130) will be individually randomised in a single-blinded, controlled trial. Participants will be 18 years of age or older, admitted to the hospital with a clean, dry and infection-free chronic foot ulcer between 2 and 20 cm2 in size. If the ulcer is infected, it will be treated before enrolment into the study. The intervention involves the application of leukocyte and platelet-rich fibrin (L-PRF) matrix on the ulcer beds during twice-weekly dressing changes. Controls receive usual care in the form of saline dressings only during their twice-weekly dressing changes. Primary outcomes are the rate of healing assessed using standardised photographs by observers blind to allocated treatment, and time to complete re-epithelialization. Follow-up is at 6 months from randomisation. DISCUSSION: This research will provide valuable information on the clinical and cost-effectiveness of L-PRF in the treatment of leprosy ulcers. An additional benefit is the evaluation of the effects of treatment on quality of life for people living with leprosy ulcers. The results will improve our understanding of the scalability of this treatment across low-income countries for ulcer healing in leprosy and potentially other conditions such as diabetic ulcers. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN14933421 . Registered on 16 June 2020.

Development of a video-observation method for examining doctors' clinical and interpersonal skills in a hospital outpatient clinic in Ibadan, Oyo State, Nigeria.

BACKGROUND: Improving the quality of primary healthcare provision is a key goal in low-and middle-income countries (LMICs). However, to develop effective quality improvement interventions, we first need to be able to accurately measure the quality of care. The methods most commonly used to measure the technical quality of care all have some key limitations in LMICs settings. Video-observation is appealing but has not yet been used in this context. We examine preliminary feasibility and acceptability of video-observation for assessing physician quality in a hospital outpatients' department in Nigeria. We also develop measurement procedures and examine measurement characteristics. METHODS: Cross-sectional study at a large tertiary care hospital in Ibadan, Nigeria. Consecutive physician-patient consultations with adults and children under five seeking outpatient care were video-recorded. We also conducted brief interviews with participating physicians to gain feedback on our approach. Video-recordings were double-coded by two medically trained researchers, independent of the study team and each other, using an explicit checklist of key processes of care that we developed, from which we derived a process quality score. We also elicited a global quality rating from reviewers. RESULTS: We analysed 142 physician-patient consultations. The median process score given by both coders was 100 %. The modal overall rating category was 'above standard' (or 4 on a scale of 1-5). Coders agreed on which rating to assign only 44 % of the time (weighted Cohen's kappa = 0.26). We found in three-level hierarchical modelling that the majority of variance in process scores was explained by coder disagreement. A very high correlation of 0.90 was found between the global quality rating and process quality score across all encounters. Participating physicians liked our approach, despite initial reservations about being observed. CONCLUSIONS: Video-observation is feasible and acceptable in this setting, and the quality of consultations was high. However, we found that rater agreement is low but comparable to other modalities that involve expert clinician judgements about quality of care including in-person direct observation and case note review. We suggest ways to improve scoring consistency including careful rater selection and improved design of the measurement procedure for the process score.

Methodological issues in economic evaluations of emergency transport systems in low-income and middle-income countries.

A recent systematic review identified few papers on the economic evaluation of systems for emergency transport of acutely ill or injured patients. In addition, we found no articles dealing with the methodological challenges posed by such studies in low-income or middle-income countries. We therefore carried out an analysis of issues that are of particular salience to this important topic. This is an intellectual study in which we develop models, identify their limitations, suggest potential extensions to the models and discuss priorities for empirical studies to populate models. First, we develop a general model to calculate changes in survival contingent on the reduced time to treatment that an emergency transport system is designed to achieve. Second, we develop a model to estimate transfer times over an area that will be served by a proposed transfer system. Third, we discuss difficulties in obtaining parameters with which to populate the models. Fourth, we discuss costs, both direct and indirect, of an emergency transfer service. Fifth, we discuss the issue that outcomes other than survival should be considered and that the effects of a service are a weighted sum over all the conditions and severities for which the service caters. Lastly, based on the above work, we identify priorities for research. To our knowledge, this is the first study to identify and frame issues in the health economics of acute transfer systems and to develop models to calculate survival rates from basic parameters, such as time delay/survival relationships, that vary by intervention type and context.

Design and analysis of three-arm parallel cluster randomized trials with small numbers of clusters.

In this article, we review and evaluate a number of methods used in the design and analysis of small three-arm parallel cluster randomized trials. We conduct a simulation-based study to evaluate restricted randomization methods including covariate-constrained randomization and a novel method for matched-group cluster randomization. We also evaluate the appropriate modelling of the data and small sample inferential methods for a variety of treatment effects relevant to three-arm trials. Our results indicate that small-sample corrections are required for high (0.05) but not low (0.001) values of the intraclass correlation coefficient and their performance can depend on trial design, number of clusters, and the nature of the hypothesis being tested. The Satterthwaite correction generally performed best at an ICC of 0.05 with a nominal type I error rate for single-period trials, and in trials with repeated measures type I error rates were between 0.04 and 0.06. Restricted randomization methods produce little benefit in trials with repeated measures but in trials with single post-intervention design can provide relatively large gains in power when compared to the most unbalanced possible allocations. Matched-group randomization improves power but is not as effective as covariate-constrained randomization. For model-based analysis, adjusting for fewer covariates than were used in a restricted randomization process under any design can produce non-nominal type I error rates and reductions in power. Where comparisons to two-arm cluster trials are possible, the performance of the methods is qualitatively very similar.