Feasibility of a cluster randomized controlled trial on the effectiveness of peer-led health education interventions to increase uptake of retinal examination for diabetic retinopathy in Kirinyaga, Kenya: a pilot trial.

BACKGROUND: People living with diabetes can reduce their risk of vision loss from diabetic retinopathy by attending screening, which enables early detection and timely treatment. The aim of this pilot trial was to assess the feasibility of a full-scale cluster randomized controlled trial of an intervention to increase uptake of retinal examination in this population, as delivered within existing community-based diabetes support groups (DSGs). METHODS: All 16 DSGs in Kirinyaga county were invited to participate in the study. The first two groups recruited took part in the pilot trial. DSG members who met the eligibility criteria were recruited before the groups that were randomized to the two arms. In the intervention group, two peer educators were trained to deliver monthly DSG-based eye health education and individual telephone reminders to attend screening. The control group continued with usual DSG practice which is monthly meetings without eye health education. The recruitment team and outcome assessors were masked to the allocation. We documented the study processes to ascertain the feasibility, acceptability, and potential effectiveness of the intervention. Feasibility was assessed in terms of clarity of study procedures, recruitment and retention rates, level of acceptability, and rates of uptake of eye examination. We set the target feasibility criteria for continuation to the main study to be recruitment of 50 participants in the trial, 80% monthly follow-up rates for individuals, and no attrition of clusters. RESULTS: Of the 122 DSG members who were assessed for eligibility, 104 were recruited and followed up: 51 (intervention) and 53 (control) arm. The study procedures were well understood and easy to apply. We learnt the DSG meeting days were the best opportunities for recruitment. The study had a high acceptance rate (100% for clusters, 95% for participants) and high follow-up and retention rate (100% of those recruited). All clusters and participants were analysed. We observed that the rate of incidence of eye exam was about 6 times higher in the intervention arm as compared to the control arm. No adverse unexpected events were reported in either arm. CONCLUSIONS: The study is feasible and acceptable in the study population. The results support the development of a full-scale cluster RCT, as the success criteria for the pilot were met. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201707002430195 Registered on 25 July 2017.

Peer-support to increase uptake of screening for diabetic retinopathy: process evaluation of the DURE cluster randomized trial.

BACKGROUND: There is limited evidence on how implementation of peer support interventions influences effectiveness, particularly for individuals with diabetes. We conducted a cluster randomized controlled trial to compare the effectiveness of a peer-led health education package versus usual care to increase uptake of screening for diabetic retinopathy (DR). METHODS: Our process evaluation used a mixed-method design to investigate the recruitment and retention, reach, dose, fidelity, acceptability, and context of implementation, and was guided by the Consolidated Framework for Implementation Research (CFIR). We reviewed trial documents, conducted semi-structured interviews with key informants (n = 10) and conducted four focus group discussions with participants in both arms of the trial. Three analysts undertook CFIR theory-driven content analysis of the qualitative data. Quantitative data was analyzed to provide descriptive statistics relevant to the objectives of the process evaluation. RESULTS: The trial had positive implementation outcomes, 100% retention of clusters and 96% retention for participants, 83% adherence to delivery of content of group talks (fidelity), and 78% attendance (reach) to at least 50% (3/6) of the group talks (dose). The data revealed that intervention characteristics, outer setting, inner setting, individual characteristics, and process (all the constructs of CFIR) influenced the implementation. There were more facilitators than barriers to the implementation. Facilitators included the relative advantage of the intervention compared with current practice (intervention characteristics); awareness of the growing prioritization of diabetes in the national health policy framework (outer setting); tension for change due to the realization of the vulnerability to vision loss from DR (inner setting); a strong collective sense of accountability of peer supporters to implement the intervention (individual characteristics); and regular feedback on the progress with implementation (process). Potential barriers included the need to queue at the eye clinic (intervention characteristic), travel inconveniences (inner setting), and socio-political disruption (outer setting). CONCLUSIONS: The intervention was implemented with high retention, reach, fidelity, and dose. The CFIR provided a valuable framework for evaluating contextual factors that influenced implementation and helped to understand what adaptations may be needed during scale up. TRIAL REGISTRATION: Pan African Clinical Trials Registry: PACTR201707002430195 registered 15 July 2017.

Diagnostic Accuracy of Unattended Automated Office Blood Pressure Measurement in Screening for Hypertension in Kenya.

Despite increasing adoption of unattended automated office blood pressure (uAOBP) measurement for determining clinic blood pressure (BP), its diagnostic performance in screening for hypertension in low-income settings has not been determined. We determined the validity of uAOBP in screening for hypertension, using 24-hour ambulatory BP monitoring as the reference standard. We studied a random population sample of 982 Kenyan adults; mean age, 42 years; 60% women; 2% with diabetes mellitus; none taking antihypertensive medications. We calculated sensitivity using 3 different screen positivity cutoffs (≥130/80, ≥135/85, and ≥140/90 mm Hg) and other measures of validity/agreement. Mean 24-hour ambulatory BP monitoring systolic BP was similar to mean uAOBP systolic BP (mean difference, 0.6 mm Hg; 95% CI, -0.6 to 1.9), but the 95% limits of agreement were wide (-39 to 40 mm Hg). Overall discriminatory accuracy of uAOBP was the same (area under receiver operating characteristic curves, 0.66-0.68; 95% CI range, 0.64-0.71) irrespective of uAOBP cutoffs used. Sensitivity of uAOBP displayed an inverse association (P<0.001) with the cutoff selected, progressively decreasing from 67% (95% CI, 62-72) when using a cutoff of ≥130/80 mm Hg to 55% (95% CI, 49-60) at ≥135/85 mm Hg to 44% (95% CI, 39-49) at ≥140/90 mm Hg. Diagnostic performance was significantly better (P<0.001) in overweight and obese individuals (body mass index, >25 kg/m2). No differences in results were present in other subanalyses. uAOBP misclassifies significant proportions of individuals undergoing screening for hypertension in Kenya. Additional studies on how to improve screening strategies in this setting are needed.

Effectiveness of peer support to increase uptake of retinal examination for diabetic retinopathy: study protocol for the DURE pragmatic cluster randomized clinical trial in Kirinyaga, Kenya.

BACKGROUND: All patients with diabetes are at risk of developing diabetic retinopathy (DR), a progressive and potentially blinding condition. Early treatment of DR prevents visual impairment and blindness. The natural history of DR is that it is asymptomatic until the advanced stages, thus annual retinal examination is recommended for early detection. Previous studies show that the uptake of regular retinal examination among people living with diabetes (PLWD) is low. In the Uptake of Retinal Examination in Diabetes (DURE) study, we will investigate the effectiveness of a complex intervention delivered within diabetes support groups to increase uptake of retinal examination. METHODS: The DURE study will be a two-arm pragmatic cluster randomized clinical trial in Kirinyaga County, Kenya. Diabetes support groups will be randomly assigned to either the intervention or usual care conditions in a 1:1 ratio. The participants will be 700 PLWD who are members of support groups in Kirinyaga. To reduce contamination, the unit of randomization will be the support group. Peer supporters in the intervention arm will receive training to deliver the intervention. The intervention will include monthly group education on DR and individual member reminders to take the eye examination. The effectiveness of this intervention plus usual care will be compared to usual care practices alone. Participant data will be collected at baseline. The primary outcome is the proportion of PLWD who take up the eye examination at six months. Secondary outcomes include the characteristics of participants and peer supporters associated with uptake of eye examination for DR. Intention-to-treat analysis will be used to evaluate the primary and secondary outcomes. DISCUSSION: Eye care programs need evidence of the effectiveness of peer supporter-led health education to improve attendance to retinal screening for the early detection of DR in an African setting. Given that the intervention combines standardization and flexibility, it has the potential to be adopted in other settings and to inform policies to promote DR screening. TRIAL REGISTRATION: Pan African Clinical Trial Registry PACTR201707002430195 , registered 25 July 2017, www.pactr.org.

Adapting clinical practice guidelines for diabetic retinopathy in Kenya: process and outputs.

BACKGROUND: The use of clinical practice guidelines envisages augmenting quality and best practice in clinical outcomes. Generic guidelines that are not adapted for local use often fail to produce these outcomes. Adaptation is a systematic and rigorous process that should maintain the quality and validity of the guideline, while making it more usable by the targeted users. Diverse skills are required for the task of adaptation. Although adapting a guideline is not a guarantee that it will be implemented, adaptation may improve acceptance and adherence to its recommendations. METHODS: We describe the process used to adapt clinical guidelines for diabetic retinopathy in Kenya, using validated tools and manuals. A technical working group consisting of volunteers provided leadership. RESULTS: The process was intensive and required more time than anticipated. Flexibility in the process and concurrent health system activities contributed to the success of the adaptation. The outputs from the adaptation include the guidelines in different formats, point of care instruments, as well as tools for training, monitoring, quality assurance and patient education. CONCLUSION: Guideline adaptation is applicable and feasible at the national level in Kenya. However, it is labor- and time -intensive. It presents a valuable opportunity to develop several additional outputs that are useful at the point of care.

Insecticide-Treated Nets and Protection against Insecticide-Resistant Malaria Vectors in Western Kenya.

Insecticide resistance might reduce the efficacy of malaria vector control. In 2013 and 2014, malaria vectors from 50 villages, of varying pyrethroid resistance, in western Kenya were assayed for resistance to deltamethrin. Long-lasting insecticide-treated nets (LLIN) were distributed to households at universal coverage. Children were recruited into 2 cohorts, cleared of malaria-causing parasites, and tested every 2 weeks for reinfection. Infection incidence rates for the 2 cohorts were 2.2 (95% CI 1.9-2.5) infections/person-year and 2.8 (95% CI 2.5-3.0) infections/person-year. LLIN users had lower infection rates than non-LLIN users in both low-resistance (rate ratio 0.61, 95% CI 0.42-0.88) and high-resistance (rate ratio 0.55, 95% CI 0.35-0.87) villages (p = 0.63). The association between insecticide resistance and infection incidence was not significant (p = 0.99). Although the incidence of infection was high among net users, LLINs provided significant protection (p = 0.01) against infection with malaria parasite regardless of vector insecticide resistance.

Predictors of uptake of eye examination in people living with diabetes mellitus in three counties of Kenya.

BACKGROUND: Diabetic retinopathy (DR) is a significant public health concern that is potentially blinding. Clinical practice guidelines recommend annual eye examination of patients with diabetes for early detection of DR. Our aim was to identify the demand-side factors that influence uptake of eye examination among patients already utilizing diabetes services in three counties of Kenya. METHODS: We designed a clinic based cross-sectional study and used three-stage sampling to select three counties, nine diabetes clinics in these counties and 270 patients with diabetes attending these clinics. We interviewed the participants using a structured questionnaire. The two outcomes of interest were 'eye examination in the last 12 months' and 'eye examination ever'. The exposure variables were the characteristics of participants living with diabetes. RESULTS: The participants had a mean age of 53.3 years (SD 14.1) and an average interval of 4 months between visits to the diabetes clinic. Only 25.6% of participants had ever had an eye examination in their lifetime, while 13.3% had it in the preceding year. The independent predictors of uptake were referral by diabetes services, patient knowledge of diabetes eye complications, comorbid hypertension and urban or semi-urban residence. CONCLUSIONS: We conclude that access to retinal examination for DR is low in all three counties. An intervention that increases the knowledge of patients with diabetes about eye complications and promotes referral of patients with diabetes for eye examination may improve access to annual eye examination for DR.

Design of a study to determine the impact of insecticide resistance on malaria vector control: a multi-country investigation.

BACKGROUND: Progress in reducing the malaria disease burden through the substantial scale up of insecticide-based vector control in recent years could be reversed by the widespread emergence of insecticide resistance. The impact of insecticide resistance on the protective effectiveness of insecticide-treated nets (ITN) and indoor residual spraying (IRS) is not known. A multi-country study was undertaken in Sudan, Kenya, India, Cameroon and Benin to quantify the potential loss of epidemiological effectiveness of ITNs and IRS due to decreased susceptibility of malaria vectors to insecticides. The design of the study is described in this paper. METHODS: Malaria disease incidence rates by active case detection in cohorts of children, and indicators of insecticide resistance in local vectors were monitored in each of approximately 300 separate locations (clusters) with high coverage of malaria vector control over multiple malaria seasons. Phenotypic and genotypic resistance was assessed annually. In two countries, Sudan and India, clusters were randomly assigned to receive universal coverage of ITNs only, or universal coverage of ITNs combined with high coverage of IRS. Association between malaria incidence and insecticide resistance, and protective effectiveness of vector control methods and insecticide resistance were estimated, respectively. RESULTS: Cohorts have been set up in all five countries, and phenotypic resistance data have been collected in all clusters. In Sudan, Kenya, Cameroon and Benin data collection is due to be completed in 2015. In India data collection will be completed in 2016. DISCUSSION: The paper discusses challenges faced in the design and execution of the study, the analysis plan, the strengths and weaknesses, and the possible alternatives to the chosen study design.

Pyrethroid susceptibility of malaria vectors in four Districts of western Kenya.

BACKGROUND: Increasing pyrethroid resistance in malaria vectors has been reported in western Kenya where long lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the mainstays of vector control. To ensure the sustainability of insecticide-based malaria vector control, monitoring programs need to be implemented. This study was designed to investigate the extent and distribution of pyrethroid resistance in 4 Districts of western Kenya (Nyando, Rachuonyo, Bondo and Teso). All four Districts have received LLINs while Nyando and Rachuonyo Districts have had IRS campaigns for 3-5 years using pyrethroids. This study is part of a programme aimed at determining the impact of insecticide resistance on malaria epidemiology. METHODS: Three day old adult mosquitoes from larval samples collected in the field, were used for bioassays using the WHO tube bioassay, and mortality recorded 24 hours post exposure. Resistance level was assigned based on the 2013 WHO guidelines where populations with <90% mortality were considered resistant. Once exposed, samples were identified to species using PCR. RESULTS: An. arabiensis comprised at least 94% of all An. gambiae s.l. in Bondo, Rachuonyo and Nyando. Teso was a marked contrast case with 77% of all samples being An. gambiae s.s. Mortality to insecticides varied widely between clusters even in one District with mortality to deltamethrin ranging from 45-100%, while to permethrin the range was 30-100%. Mortality to deltamethrin in Teso District was < 90% in 4 of 6 clusters tested in An arabiensis and <90% in An. gambiae s.s in 5 of 6 clusters tested. To permethrin, mortality ranged between 5.9-95%, with <90% mortality in 9 of 13 and 8 of 13 in An. arabiensis and An. gambiae s.s. respectively. Cluster specific mortality of An. arabiensis between permethin and deltamethrin were not correlated (Z = 2.9505, P = 0.2483). CONCLUSION: High levels of pyrethroid resistance were observed in western Kenya. This resistance does not seem to be associated with either species or location. Insecticide resistance can vary within small geographical areas and such heterogeneity may make it possible to evaluate the impact of resistance on malaria and mosquito parameters within similar eco-epidemiological zones.

Geographical variation in the response of visceral leishmaniasis to paromomycin in East Africa: a multicentre, open-label, randomized trial.

BACKGROUND: Visceral leishmaniasis (VL) is a major health problem in developing countries. The untreated disease is fatal, available treatment is expensive and often toxic, and drug resistance is increasing. Improved treatment options are needed. Paromomycin was shown to be an efficacious first-line treatment with low toxicity in India. METHODS: This was a 3-arm multicentre, open-label, randomized, controlled clinical trial to compare three treatment regimens for VL in East Africa: paromomycin sulphate (PM) at 15 mg/kg/day for 21 days versus sodium stibogluconate (SSG) at 20 mg/kg/day for 30 days; and the combination of both dose regimens for 17 days. The primary efficacy endpoint was cure based on parasite-free tissue aspirates taken 6 months after treatment. FINDINGS: Overall, 135 patients per arm were enrolled at five centres in Sudan (2 sites), Kenya (1) and Ethiopia (2), when the PM arm had to be discontinued due to poor efficacy. The trial has continued with the higher dose of PM as well as the combination of PM and SSG arms. These results will be reported later. Baseline patient characteristics were similar among treatment arms. The overall cure with PM was significantly inferior to that with SSG (63.8% versus 92.2%; difference 28.5%, 95%CI 18.8% to 38.8%, p<0.001). The efficacy of PM varied among centres and was significantly lower in Sudan (14.3% and 46.7%) than in Kenya (80.0%) and Ethiopia (75.0% and 96.6%). No major safety issues with PM were identified. CONCLUSION: The efficacy of PM at 15 mg/kg/day for 21 days was inadequate, particularly in Sudan. The efficacy of higher doses and the combination treatment warrant further studies.

Markers in HIV associated tuberculosis in Kenya.

Tuberculosis is one of the most frequent opportunistic infections in HIV-infected patients in developing countries. In some instances, manifestations of pulmonary tuberculosis precede all other HIV related signs and symptoms because of the high virulence of M. tuberculosis. In order to characterise the interaction between these two pathogens, clinical and immunological parameters in pulmonary tuberculosis patients with and without HIV infection were compared. Amongst newly diagnosed pulmonary tuberculosis patients the association of some of these changes with the clinical outcome were evaluated. Of these, 44% were co-infected with HIV. Pulmonary tuberculosis patients with HIV-1 presented more frequently with lymphadenopathy and diarrhoea than those without HIV-1. Peripheral blood CD4+ counts were significantly lower in patients with pulmonary tuberculosis with HIV-1 than those with pulmonary tuberculosis alone, P= 0.0292. Low CD4+ lymphocyte counts, lymphadenopathy and BCG scar absence could serve as indicators of HIV-1 infection in pulmonary tuberculosis (PTB) patients.