Mapping social capital across Wales (UK) using secondary data and spatial analysis.

Social capital, a powerful community resource based on trust, relationships, norms, culture, values, networks and belonging, could shape the acceptance, cooperation, and involvement of citizens towards new policies or interventions. In past, connections of social capital have been studied in relation to human health, wellbeing, social and economic development. More recently, social capital has been studied with respect to human resilience and adaptation to climate change. We argue that social capital could also play a vital role in our efforts to reduce carbon footprint through behaviour change, a shift on shared local renewable energy resources, and adoption of low carbon technologies. In Wales (UK) there is no national scale dataset, reflecting its social capital landscape, that could be used for designing the right policies/interventions in this context, based on an expected level of trust, cooperation, and support within the communities. This paper is an effort to fill this data gap using secondary datasets. Firstly, a literature review is carried out to identify the indicators of social capital (cognitive and participatory). Secondary datasets have then been identified and acquired. Geospatial analysis has been carried out to produce the criterion maps for various indicators of social capital. Finally, Analytical Hierarchy Process is applied to generate a social capital map of Wales combining these indicators together. For validation of the produced data, social capital's known correlations were tested with crime rates, income level and multiple deprivations. Supplementary Information: The online version contains supplementary material available at 10.1007/s43545-023-00639-1.

Evaluation of a medication monitor-based treatment strategy for drug-sensitive tuberculosis patients in China: study protocol for a cluster randomised controlled trial.

BACKGROUND: Treatment for drug-sensitive tuberculosis (TB) is taken for at least 6 months and problems with adherence are common. Therefore, there is substantial interest in the possible use of eHealth interventions to support patients to take their treatment. Electronic medication monitors have been shown to improve adherence to TB medication, but the impact on clinical outcomes is unknown. We aim to evaluate the impact of a medication monitor-based treatment strategy for drug-sensitive TB patients on a composite poor outcome measured over 18 months from start of TB treatment. METHODS/DESIGN: We will conduct an open, pragmatic, cluster randomised superiority trial, with 24 counties/districts in three provinces in China, randomised 1:1 to implement the intervention or standard of care. Adults (aged ≥ 18 years) with a new episode of GeneXpert-positive and rifampicin-sensitive pulmonary TB, who plan to be in the study area for the next 18 months, and will receive daily fixed-dose combination tablets for 6 months of treatment are eligible. The intervention is centred around a medication monitor that holds a 1-month supply of medication and has three key functions: as an audio and visual reminder for patients to take their daily medication; reminds patients of upcoming monthly visit; and records date and time whenever the box is opened. At the monthly follow-up visit, the doctor downloads these data to generate a graphical display of the last month's adherence record for discussion with the patient and potentially to switch the patient to more intensive management. The primary outcome is a composite poor outcome measured over 18 months from start of TB treatment, defined as either of poor outcome at the end of treatment (death, treatment failure, or loss to follow-up) or subsequent recurrence (culture positive for TB at 12 or 18 months or re-starting TB treatment in the follow-up period). An economic evaluation will also be conducted as part of this study. DISCUSSION: This trial will assess whether a medication monitor-based treatment strategy can improve clinical outcomes for TB patients. Several trials of other eHealth interventions for TB treatment are ongoing and are summarised in this paper. This trial will provide an important part of the emerging evidence base for the potential of eHealth to improve TB treatment outcomes. TRIAL REGISTRATION: This trial was registered with Current Controlled Trials (identifier: ISRCTN35812455 ). Registered on May 19, 2016.

A randomized controlled study of socioeconomic support to enhance tuberculosis prevention and treatment, Peru.

OBJECTIVE: To evaluate the impact of socioeconomic support on tuberculosis preventive therapy initiation in household contacts of tuberculosis patients and on treatment success in patients. METHODS: A non-blinded, household-randomized, controlled study was performed between February 2014 and June 2015 in 32 shanty towns in Peru. It included patients being treated for tuberculosis and their household contacts. Households were randomly assigned to either the standard of care provided by Peru's national tuberculosis programme (control arm) or the same standard of care plus socioeconomic support (intervention arm). Socioeconomic support comprised conditional cash transfers up to 230 United States dollars per household, community meetings and household visits. Rates of tuberculosis preventive therapy initiation and treatment success (i.e. cure or treatment completion) were compared in intervention and control arms. FINDINGS: Overall, 282 of 312 (90%) households agreed to participate: 135 in the intervention arm and 147 in the control arm. There were 410 contacts younger than 20 years: 43% in the intervention arm initiated tuberculosis preventive therapy versus 25% in the control arm (adjusted odds ratio, aOR: 2.2; 95% confidence interval, CI: 1.1-4.1). An intention-to-treat analysis showed that treatment was successful in 64% (87/135) of patients in the intervention arm versus 53% (78/147) in the control arm (unadjusted OR: 1.6; 95% CI: 1.0-2.6). These improvements were equitable, being independent of household poverty. CONCLUSION: A tuberculosis-specific, socioeconomic support intervention increased uptake of tuberculosis preventive therapy and tuberculosis treatment success and is being evaluated in the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project.

Socioeconomic Determinants of Antibiotic Consumption in the State of São Paulo, Brazil: The Effect of Restricting Over-The-Counter Sales.

BACKGROUND: Improper antibiotic use is one of the main drivers of bacterial resistance to antibiotics, increasing infectious diseases morbidity and mortality and raising costs of healthcare. The level of antibiotic consumption has been shown to vary according to socioeconomic determinants (SED) such as income and access to education. In many Latin American countries, antibiotics could be easily purchased without a medical prescription in private pharmacies before enforcement of restrictions on over-the-counter (OTC) sales in recent years. Brazil issued a law abolishing OTC sales in October 2010. This study seeks to find SED of antibiotic consumption in the Brazilian state of São Paulo (SSP) and to estimate the impact of the 2010 law. METHODS: Data on all oral antibiotic sales having occurred in the private sector in SSP from 2008 to 2012 were pooled into the 645 municipalities of SSP. Linear regression was performed to estimate consumption levels that would have occurred in 2011 and 2012 if no law regulating OTC sales had been issued in 2010. These values were compared to actual observed levels, estimating the effect of this law. Linear regression was performed to find association of antibiotic consumption levels and of a greater effect of the law with municipality level data on SED obtained from a nationwide census. RESULTS: Oral antibiotic consumption in SSP rose from 8.44 defined daily doses per 1,000 inhabitants per day (DID) in 2008 to 9.95 in 2010, and fell to 8.06 DID in 2012. Determinants of a higher consumption were higher human development index, percentage of urban population, density of private health establishments, life expectancy and percentage of females; lower illiteracy levels and lower percentage of population between 5 and 15 years old. A higher percentage of females was associated with a stronger effect of the law. CONCLUSIONS: SSP had similar antibiotic consumption levels as the whole country of Brazil, and they were effectively reduced by the policy.

The economic effects of supporting tuberculosis-affected households in Peru.

The End TB Strategy mandates that no tuberculosis (TB)-affected households face catastrophic costs due to TB. However, evidence is limited to evaluate socioeconomic support to achieve this change in policy and practice. The objective of the present study was to investigate the economic effects of a TB-specific socioeconomic intervention.The setting was 32 shantytown communities in Peru. The participants were from households of consecutive TB patients throughout TB treatment administered by the national TB programme. The intervention consisted of social support through household visits and community meetings, and economic support through cash transfers conditional upon TB screening in household contacts, adhering to TB treatment/chemoprophylaxis and engaging with social support. Data were collected to assess TB-affected household costs. Patient interviews were conducted at treatment initiation and then monthly for 6 months.From February 2014 to June 2015, 312 households were recruited, of which 135 were randomised to receive the intervention. Cash transfer total value averaged US$173 (3.5% of TB-affected households' average annual income) and mitigated 20% of households' TB-related costs. Households randomised to receive the intervention were less likely to incur catastrophic costs (30% (95% CI 22-38%) versus 42% (95% CI 34-51%)). The mitigation impact was higher among poorer households.The TB-specific socioeconomic intervention reduced catastrophic costs and was accessible to poorer households. Socioeconomic support and mitigating catastrophic costs are integral to the End TB strategy, and our findings inform implementation of these new policies.

A mixed methods protocol to evaluate the effect and cost-effectiveness of an Integrated electronic Diagnosis Approach (IeDA) for the management of childhood illnesses at primary health facilities in Burkina Faso.

BACKGROUND: Burkina Faso introduced the Integrated Management of Childhood Illnesses (IMCI) strategy in 2003. However, an evaluation conducted in 2013 found that only 28 % of children were assessed for three danger signs as recommended by IMCI, and only 15 % of children were correctly classified. About 30 % of children were correctly prescribed with an antibiotic for suspected pneumonia or oral rehydration salts (ORS) for diarrhoea, and 40 % were correctly referred. Recent advances in information and communication technologies (ICT) and use of electronic clinical protocols hold the potential to transform healthcare delivery in low-income countries. However, no evidence is available on the effect of ICT on adherence to IMCI. This paper describes the research protocol of a mixed methods study that aims to measure the effect of the Integrated electronic Diagnosis Approach innovation (an electronic IMCI protocol provided to nurses) in two regions of Burkina Faso. METHODS/DESIGN: The study combines a stepped-wedge trial, a realistic evaluation and an economic study in order to capture the effect of the innovation after its introduction on the level of adherence, cost and acceptability. DISCUSSION: The main challenge is to interconnect the three substudies. In integrating outcome, process and cost data, we focus on three key questions: (i) How does the effectiveness and the cost of the intervention vary by type of health worker and type of health centre? (ii) What is the impact of changes in the content, coverage and quality of the IeDA intervention on adherence and cost-effectiveness? (iii) What mechanisms of change (including costs) might explain the relationship between the IeDA intervention and adherence? TRIAL REGISTRATION: Clinicaltrials.gov, NCT02341469 .

Cost-Effectiveness of Automated Digital Microscopy for Diagnosis of Active Tuberculosis.

BACKGROUND: Automated digital microscopy has the potential to improve the diagnosis of tuberculosis (TB), particularly in settings where molecular testing is too expensive to perform routinely. The cost-effectiveness of TB diagnostic algorithms using automated digital microscopy remains uncertain. METHODS: Using data from a demonstration study of an automated digital microscopy system (TBDx, Applied Visual Systems, Inc.), we performed an economic evaluation of TB diagnosis in South Africa from the health system perspective. The primary outcome was the incremental cost per new TB diagnosis made. We considered costs and effectiveness of different algorithms for automated digital microscopy, including as a stand-alone test and with confirmation of positive results with Xpert MTB/RIF ('Xpert', Cepheid, Inc.). Results were compared against both manual microscopy and universal Xpert testing. RESULTS: In settings willing to pay $2000 per incremental TB diagnosis, universal Xpert was the preferred strategy. However, where resources were not sufficient to support universal Xpert, and a testing volume of at least 30 specimens per day could be ensured, automated digital microscopy with Xpert confirmation of low-positive results could facilitate the diagnosis of 79-84% of all Xpert-positive TB cases, at 50-60% of the total cost. The cost-effectiveness of this strategy was $1280 per incremental TB diagnosis (95% uncertainty range, UR: $340-$3440) in the base case, but improved under conditions likely reflective of many settings in sub-Saharan Africa: $677 per diagnosis (95% UR: $450-$935) when sensitivity of manual smear microscopy was lowered to 0.5, and $956 per diagnosis (95% UR: $40-$2910) when the prevalence of multidrug-resistant TB was lowered to 1%. CONCLUSIONS: Although universal Xpert testing is the preferred algorithm for TB diagnosis when resources are sufficient, automated digital microscopy can identify the majority of cases and halve the cost of diagnosis and treatment when resources are more scarce and multidrug-resistant TB is not common.

Designing and implementing a socioeconomic intervention to enhance TB control: operational evidence from the CRESIPT project in Peru.

BACKGROUND: Cash transfers are key interventions in the World Health Organisation's post-2015 global TB policy. However, evidence guiding TB-specific cash transfer implementation is limited. We designed, implemented and refined a novel TB-specific socioeconomic intervention that included cash transfers, which aimed to support TB prevention and cure in resource-constrained shantytowns in Lima, Peru for: the Community Randomized Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT) project. METHODS: Newly-diagnosed TB patients from study-site healthposts were eligible to receive the intervention consisting of economic and social support. Economic support was provided to patient households through cash transfers on meeting the following conditions: screening for TB in household contacts and MDR TB in patients; adhering to TB treatment and chemoprophylaxis; and engaging with CRESIPT social support (household visits and community meetings). To evaluate project acceptability, quantitative and qualitative feedback was collected using a mixed-methods approach during formative activities. Formative activities included consultations, focus group discussions and questionnaires conducted with the project team, project participants, civil society and stakeholders. RESULTS: Over 7 months, 135 randomly-selected patients and their 647 household contacts were recruited from 32 impoverished shantytown communities. Of 1299 potential cash transfers, 964 (74 %) were achieved, 259 (19 %) were not achieved, and 76 (7 %) were yet to be achieved. Of those achieved, 885/964 (92 %) were achieved optimally and 79/964 (8 %) sub-optimally. Key project successes were identified during 135 formative activities and included: strong multi-sectorial collaboration; generation of new evidence for TB-specific cash transfer; and the project being perceived as patient-centred and empowering. Challenges included: participant confidence being eroded through cash transfer delays, hidden account-charges and stigma; access to the initial bank-provider being limited; and conditions requiring participation of all TB-affected household members (e.g. community meetings) being hard to achieve. Refinements were made to improve project acceptability and future impact: the initial bank-provider was changed; conditional and unconditional cash transfers were combined; cash transfer sums were increased to a locally-appropriate, evidence-based amount; and cash transfer size varied according to patient household size to maximally reduce mitigation of TB-related costs and be more responsive to household needs. CONCLUSIONS: A novel TB-specific socioeconomic intervention including conditional cash transfers has been designed, implemented, refined and is ready for impact assessment, including by the CRESIPT project. The lessons learnt during this research will inform policy-makers and decision-makers for future implementation of related interventions.

Logistic, ethical, and political dimensions of stepped wedge trials: critical review and case studies.

BACKGROUND: Three arguments are usually invoked in favour of stepped wedge cluster randomised controlled trials: the logistic convenience of implementing an intervention in phases, the ethical benefit of providing the intervention to all clusters, and the potential to enhance the social acceptability of cluster randomised controlled trials. Are these alleged benefits real? We explored the logistic, ethical, and political dimensions of stepped wedge trials using case studies of six recent evaluations. METHODS: We identified completed or ongoing stepped wedge evaluations using two systematic reviews. We then purposively selected six with a focus on public health in high, middle, and low-income settings. We interviewed their authors about the logistic, ethical, and social issues faced by their teams. Two authors reviewed interview transcripts, identified emerging issues through qualitative thematic analysis, reflected upon them in the context of the literature, and invited all participants to co-author the manuscript. RESULTS: Our analysis raises three main points. First, the phased implementation of interventions can alleviate problems linked to simultaneous roll-out, but also brings new challenges. Issues to consider include the feasibility of organising intervention activities according to a randomised sequence, estimating time lags in implementation and effects, and accommodating policy changes during the trial period. Second, stepped wedge trials, like parallel cluster trials, require equipoise: without it, randomising participants to a control condition, even for a short time, remains problematic. In stepped wedge trials, equipoise is likely to lie in the degree of effect, effectiveness in a specific operational milieu, and the balance of benefit and harm, including the social value of better evaluation. Third, the strongest arguments for a stepped wedge design are logistic and political rather than ethical. The design is advantageous when simultaneous roll-out is impractical and when it increases the acceptability of using counterfactuals. CONCLUSIONS: The logistic convenience of phased implementation is context-dependent, and may be vitiated by the additional requirements of phasing. The potential for stepped wedge trials to enhance the social acceptability of cluster randomised trials is real, but their ethical legitimacy still rests on demonstrating equipoise and its configuration for each research question and setting.

Stepped wedge randomised controlled trials: systematic review of studies published between 2010 and 2014.

BACKGROUND: In a stepped wedge, cluster randomised trial, clusters receive the intervention at different time points, and the order in which they received it is randomised. Previous systematic reviews of stepped wedge trials have documented a steady rise in their use between 1987 and 2010, which was attributed to the design's perceived logistical and analytical advantages. However, the interventions included in these systematic reviews were often poorly reported and did not adequately describe the analysis and/or methodology used. Since 2010, a number of additional stepped wedge trials have been published. This article aims to update previous systematic reviews, and consider what interventions were tested and the rationale given for using a stepped wedge design. METHODS: We searched PubMed, PsychINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Web of Science, the Cochrane Library and the Current Controlled Trials Register for articles published between January 2010 and May 2014. We considered stepped wedge randomised controlled trials in all fields of research. We independently extracted data from retrieved articles and reviewed them. Interventions were then coded using the functions specified by the Behaviour Change Wheel, and for behaviour change techniques using a validated taxonomy. RESULTS: Our review identified 37 stepped wedge trials, reported in 10 articles presenting trial results, one conference abstract, 21 protocol or study design articles and five trial registrations. These were mostly conducted in developed countries (n = 30), and within healthcare organisations (n = 28). A total of 33 of the interventions were educationally based, with the most commonly used behaviour change techniques being 'instruction on how to perform a behaviour' (n = 32) and 'persuasive source' (n = 25). Authors gave a wide range of reasons for the use of the stepped wedge trial design, including ethical considerations, logistical, financial and methodological. The adequacy of reporting varied across studies: many did not provide sufficient detail regarding the methodology or calculation of the required sample size. CONCLUSIONS: The popularity of stepped wedge trials has increased since 2010, predominantly in high-income countries. However, there is a need for further guidance on their reporting and analysis.

Systematic review of strategies to increase men's HIV-testing in sub-Saharan Africa.

OBJECTIVE: This systematic review summarizes evidence on the effectiveness of strategies to increase men's HIV-testing in sub-Saharan Africa. METHODS: Medline, EmBase, Africa-Wide Information and Global Health were searched. Cluster and individually randomized trials evaluating interventions to increase the proportion of adults (≥ 15 years) testing for HIV were eligible if they were conducted in sub-Saharan Africa, included men in the study population, and reported HIV-testing data by sex. References were independently screened. RESULTS: Of the 1852 references, 15 papers including 16 trials were eligible. Trials were judged too heterogeneous to combine in meta-analysis. Three interventions invited men to attend antenatal care-based HIV-testing via pregnant partners, of which two showed a significant effect on partner-testing. One intervention invited men to HIV-test through pregnant partners and showed an increase in HIV-testing when it was offered in bars compared with health facilities. A trial of notification to partners of newly diagnosed HIV-positive patients showed an increase in testing where notification was by healthcare providers compared with notification by the patient. Three interventions reached men already at health facilities and eight reported the effects of community-based HIV testing. Mobile-testing had a significant effect on HIV-testing compared with standard voluntary counselling and testing. Home-based testing also had a significant effect, but reached smaller numbers of men than mobile-testing. DISCUSSION: Interventions to encourage HIV-testing can increase men's levels of HIV testing. Community-based programmes in particular had a large effect on population levels of HIV-testing. More data on costs and potential population impact of these approaches over different time-horizons would aid policy-makers in planning resource allocation to increase male HIV-testing.

Mortality associated with delays between clinic entry and ART initiation in resource-limited settings: results of a transition-state model.

OBJECTIVE: To estimate the mortality impact of delay in antiretroviral therapy (ART) initiation from the time of entry into care. DESIGN: A state-transition Markov process model. This technique allows for assessing mortality before and after ART initiation associated with delays in ART initiation among a general population of ART-eligible patients without conducting a randomized trial. METHODS: We used patient-level data from 3 South African cohorts to determine transition probabilities for pre-ART CD4 count changes and pre-ART and on-ART mortality. For each parameter, we generated probabilities and distributions for Monte Carlo simulations with 1-week cycles to estimate mortality 52 weeks from clinic entry. RESULTS: We estimated an increase in mortality from 11.0% to 14.7% (relative increase of 34%) with a 10-week delay in ART for patients entering care with our pre-ART cohort CD4 distribution. When we examined low CD4 ranges, the relative increase in mortality delays remained similar; however, the absolute increase in mortality rose. For example, among patients entering with CD4 count 50-99 cells per cubic millimeter, 12-month mortality increased from 13.3% with no delay compared with 17.0% with a 10-week delay and 22.9% with a 6-month delay. CONCLUSIONS: Delays in ART initiation, common in routine HIV programs, can lead to important increases in mortality. Prompt ART initiation for patients entering clinical care and eligible for ART, especially those with lower CD4 counts, could be a relatively low-cost approach with a potential marked impact on mortality.

Antiretroviral treatment cohort analysis using time-updated CD4 counts: assessment of bias with different analytic methods.

BACKGROUND: Survival analysis using time-updated CD4+ counts during antiretroviral therapy is frequently employed to determine risk of clinical events. The time-point when the CD4+ count is assumed to change potentially biases effect estimates but methods used to estimate this are infrequently reported. METHODS: This study examined the effect of three different estimation methods: assuming i) a constant CD4+ count from date of measurement until the date of next measurement, ii) a constant CD4+ count from the midpoint of the preceding interval until the midpoint of the subsequent interval and iii) a linear interpolation between consecutive CD4+ measurements to provide additional midpoint measurements. Person-time, tuberculosis rates and hazard ratios by CD4+ stratum were compared using all available CD4+ counts (measurement frequency 1-3 months) and 6 monthly measurements from a clinical cohort. Simulated data were used to compare the extent of bias introduced by these methods. RESULTS: The midpoint method gave the closest fit to person-time spent with low CD4+ counts and for hazard ratios for outcomes both in the clinical dataset and the simulated data. CONCLUSION: The midpoint method presents a simple option to reduce bias in time-updated CD4+ analysis, particularly at low CD4 cell counts and rapidly increasing counts after ART initiation.

Antiretrovirals and isoniazid preventive therapy in the prevention of HIV-associated tuberculosis in settings with limited health-care resources.

Antiretroviral therapy and isoniazid preventive therapy (IPT) are both effective interventions to prevent HIV-associated tuberculosis, but work via different mechanisms. We propose that these two interventions might best be used as complementary strategies at different stages of HIV progression. At relatively high CD4-cell counts, IPT reduces tuberculosis risk by 64% (95% CI 39-78%) in patients with positive tuberculin skin tests, and is the key tuberculosis preventive intervention before patients are eligible for antiretroviral therapy. However, at low CD4-cell counts, reliable exclusion of active tuberculosis is difficult, fewer patients are eligible for IPT, and waning immune function might limit the durability of its effect. In such patients, antiretroviral therapy is the primary intervention needed, reducing tuberculosis incidence by 67% (95% CI 61-73%). However, tuberculosis risk during long-term antiretroviral therapy remains several times higher than background, especially in those with poor immune recovery. Patients might therefore derive additional benefit from combined use of IPT and antiretroviral therapy to simultaneously treat mycobacterial infection and restore tuberculosis-specific immune function. For those first presenting with advanced immunodeficiency, we propose that concurrent IPT might best be delayed until completion of the first few months of antiretroviral therapy, when active tuberculosis can be more reliably excluded. Data from randomised controlled trials are needed to underpin further development of public-health policy.