Treatment of fevers prior to introducing rapid diagnostic tests for malaria in registered drug shops in Uganda.

BACKGROUND: Since drug shops play an important role in treatment of fever, introducing rapid diagnostic tests (RDTs) for malaria at drug shops may have the potential of targeting anti-malarial drugs to those with malaria parasites and improve rational drug use. As part of a cluster randomized trial to examine impact on appropriate treatment of malaria in drug shops in Uganda and adherence to current malaria treatment policy guidelines, a survey was conducted to estimate baseline prevalence of, and factors associated with, appropriate treatment of malaria to enable effective design and implementation of the cluster randomized trial. METHODS: A survey was conducted within 20 geographical clusters of drug shops from May to September 2010 in Mukono district, central Uganda. A cluster was defined as a parish representing a cluster of drug shops. Data was collected using two structured questionnaires: a provider questionnaire to capture data on drug shops (n=65) including provider characteristics, knowledge on treatment of malaria, previous training received, type of drugs stocked, reported drug sales, and record keeping practices; and a patient questionnaire to capture data from febrile patients (n=540) exiting drug shops on presenting symptoms, the consultation process, treatment received, and malaria diagnoses. Malaria diagnosis made by drug shop vendors were confirmed by the study team through microscopy examination of a blood slide to ascertain whether appropriate treatment was received. RESULTS: Among febrile patients seen at drug shops, 35% had a positive RDT result and 27% had a positive blood slide. Many patients (55%) had previously sought care from another drug shop prior to this consultation. Three quarters (73%) of all febrile patients seen at drug shops received an anti-malarial, of whom 39% received an ACT and 33% received quinine. The rest received another non-artemisinin monotherapy. Only one third (32%) of patients with a positive blood slide had received treatment with Coartem® while 34% of those with a negative blood slide had not received an anti-malarial. Overall appropriate treatment was 34 (95% CI: 28 - 40) with substantial between-cluster variation, ranging from 1% to 55%. CONCLUSION: In this setting, the proportion of malaria patients receiving appropriate ACT treatment at drug shops was low. This was due to the practice of presumptive treatment, inadequate training on malaria management and lack of knowledge that Coartem® was the recommended first-line treatment for malaria. There is urgent need for interventions to improve treatment of malaria at these outlets

Economic evaluation of a cluster randomized trial of interventions to improve health workers' practice in diagnosing and treating uncomplicated malaria in Cameroon.

BACKGROUND: Malaria rapid diagnostic tests (RDTs) are a valid alternative to malaria testing with microscopy and are recommended for the testing of febrile patients before prescribing an antimalarial. There is a need for interventions to support the uptake of RDTs by health workers. OBJECTIVE: To evaluate the cost-effectiveness of introducing RDTs with basic or enhanced training in health facilities in which microscopy was available, compared with current practice. METHODS: A three-arm cluster randomized trial was conducted in 46 facilities in central and northwest Cameroon. Basic training had a practical session on RDTs and lectures on malaria treatment guidelines. Enhanced training included small-group activities designed to change health workers' practice and reduce the consumption of antimalarials among test-negative patients. The primary outcome was the proportion of febrile patients correctly treated: febrile patients should be tested for malaria, artemisinin combination therapy should be prescribed for confirmed cases, and no antimalarial should be prescribed for patients who are test-negative. Individual patient data were obtained from facility records and an exit survey. Costs were estimated from a societal perspective using project reports and patient exit data. The analysis used bivariate multilevel modeling and adjusted for imbalance in baseline covariates. RESULTS: Incremental cost per febrile patient correctly treated was $8.40 for the basic arm and$3.71 for the enhanced arm. On scale-up, it was estimated that RDTs with enhanced training would save $0.75 per additional febrile patient correctly treated. CONCLUSIONS: Introducing RDTs with enhanced training was more cost-effective than RDTs with basic training when each was compared with current practice

Basic or enhanced clinician training to improve adherence to malaria treatment guidelines: a cluster-randomised trial in two areas of Cameroon

Background The scale-up of malaria rapid diagnostic tests (RDTs) is intended to improve case management of fever and targeting of artemisinin-based combination therapy. Habitual presumptive treatment has hampered these intentions, suggesting a need for strategies to support behaviour change. We aimed to assess the introduction of RDTs when packaged with basic or enhanced clinician training interventions in Cameroon. Methods We did a three-arm, stratifi ed, cluster-randomised trial at 46 public and mission health facilities at two study sites in Cameroon to compare three approaches to malaria diagnosis. Facilities were randomly assigned by a computer program in a 9:19:19 ratio to current practice with microscopy (widely available, used as a control group); RDTs with a basic (1 day) clinician training intervention; or RDTs with an enhanced (3 days) clinician training intervention. Patients (or their carers) and fi eldworkers who administered surveys to obtain outcome data were masked to study group assignment. The primary outcome was the proportion of patients treated in accordance with WHO malaria treatment guidelines, which is a composite indicator of whether patients were tested for malaria and given appropriate treatment consistent with the test result. All analyses were by intention to treat. This study is registered at ClinicalTrials. gov, number NCT01350752. Findings The study took place between June 7 and Dec 14, 2011. The analysis included 681 patients from nine facilities in the control group, 1632 patients from 18 facilities in the basic-training group, and 1669 from 19 facilities in the enhanced-training group. The proportion of patients treated in accordance with malaria guidelines did not improve with either intervention; the adjusted risk ratio (RR) for basic training compared with control was 1·04 (95% CI 0·53–2·07; p=0·90), and for enhanced training compared with control was 1·17 (0·61–2·25; p=0·62). Inappropriate use of antimalarial drugs after a negative test was reduced from 84% (201/239) in the control group to 52% (413/796) in the basic-training group (unadjusted RR 0·63, 0·28–1·43; p=0·25) and to 31% (232/759) in the enhanced-training group (0·29, 0·11–0·77; p=0·02). Interpretation Enhanced clinician training, designed to translate knowledge into prescribing practice and improve quality of care, has the potential to halve overtreatment in public and mission health facilities in Cameroon. Basic training is unlikely to be suffi cient to support the behaviour change required for the introduction of RDTs

Designing and implementing interventions to change clinicians' practice in the management of uncomplicated malaria: lessons from Cameroon.

BACKGROUND: Effective case management of uncomplicated malaria is a fundamental pillar of malaria control. Little is known about the various steps in designing interventions to accompany the roll out of rapid diagnostic tests (RDTs) and artemisinin-based combination therapy (ACT). This study documents the process of designing and implementing interventions to change clinicians' practice in the management of uncomplicated malaria. METHODS: A literature review combined with formative quantitative and qualitative research were carried out to determine patterns of malaria diagnosis and treatment and to understand how malaria and its treatment are enacted by clinicians. These findings were used, alongside a comprehensive review of previous interventions, to identify possible strategies for changing the behaviour of clinicians when diagnosing and treating uncomplicated malaria. These strategies were discussed with ministry of health representatives and other stakeholders. Two intervention packages - a basic and an enhanced training were outlined, together with logic model to show how each was hypothesized to increase testing for malaria, improve adherence to test results and increase appropriate use of ACT. The basic training targeted clinicians' knowledge of malaria diagnosis, rapid diagnostic testing and malaria treatment. The enhanced training included additional modules on adapting to change, professionalism and communicating effectively. Modules were delivered using small-group work, card games, drama and role play. Interventions were piloted, adapted and trainers were trained before final implementation. RESULTS: Ninety-six clinicians from 37 health facilities in Bamenda and Yaounde sites attended either 1-day basic or 3-day enhanced training. The trained clinicians then trained 632 of their peers at their health facilities. Evaluation of the training revealed that 68% of participants receiving the basic and 92% of those receiving the enhanced training strongly agreed that it is not appropriate to prescribe anti-malarials to a patient if they have a negative RDT result. CONCLUSION: Formative research was an important first step, and it was valuable to engage stakeholders early in the process. A logic model and literature reviews were useful to identify key elements and mechanisms for behaviour change intervention. An iterative process with feedback loops allowed appropriate development and implementation of the intervention. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01350752

A cost-effectiveness analysis of provider and community interventions to improve the treatment of uncomplicated malaria in Nigeria: study protocol for a randomized controlled trial.

BACKGROUND: There is mounting evidence of poor adherence by health service personnel to clinical guidelines for malaria following a symptomatic diagnosis. In response to this, the World Health Organization (WHO) recommends that in all settings clinical suspicion of malaria should be confirmed by parasitological diagnosis using microscopy or Rapid Diagnostic Test (RDT). The Government of Nigeria plans to introduce RDTs in public health facilities over the coming year. In this context, we will evaluate the effectiveness and cost-effectiveness of two interventions designed to support the roll-out of RDTs and improve the rational use of ACTs. It is feared that without supporting interventions, non-adherence will remain a serious impediment to implementing malaria treatment guidelines. METHODS/DESIGN: A three-arm stratified cluster randomized trial is used to compare the effectiveness and cost-effectiveness of: (1) provider malaria training intervention versus expected standard practice in malaria diagnosis and treatment; (2) provider malaria training intervention plus school-based intervention versus expected standard practice; and (3) the combined provider plus school-based intervention versus provider intervention alone. RDTs will be introduced in all arms of the trial. The primary outcome is the proportion of patients attending facilities that report a fever or suspected malaria and receive treatment according to malaria guidelines. This will be measured by surveying patients (or caregivers) as they exit primary health centers, pharmacies, and patent medicine dealers. Cost-effectiveness will be presented in terms of the primary outcome and a range of secondary outcomes, including changes in provider and community knowledge. Costs will be estimated from both a societal and provider perspective using standard economic evaluation methodologies. TRIAL REGISTRATION: Clinicaltrials.gov NCT01350752

Dopamine Augmented Rehabilitation in Stroke (DARS): a multicentre double-blind, randomised controlled trial of co-careldopa compared with placebo, in addition to routine NHS occupational and physical therapy, delivered early after stroke on functional recovery

BACKGROUND: Dopamine is a key modulator of striatal function and learning, and may improve motor recovery after stroke. Seven small trials of dopamine agonists after stroke have provided equivocal evidence of the clinical effectiveness of dopamine agonists in improving motor recovery. DESIGN: Dopamine Augmented Rehabilitation in Stroke was a multicentre, randomised, double-blind, placebo-controlled trial with stroke patients randomised to receive 6 weeks of co-careldopa (Sinemet®, Merck Sharp & Dohme Ltd) or placebo in combination with occupational and physical rehabilitation. METHODS: The primary outcome measure was the proportion of patients walking independently at 8 weeks [Rivermead Mobility Index (RMI) score of ≥ 7 points and ‘yes’ to item 7 on the RMI]. Secondary outcome measures assessed physical functioning, pain, cognition, mood, fatigue and carer burden at 8 weeks, 6 months and 12 months. RESULTS: Between May 2011 and March 2014, 593 patients (mean age 68.5 years) and 165 carers (mean age 59.7 years) were recruited from stroke rehabilitation units; 308 patients were randomised to co-careldopa and 285 to placebo at a median of 15 days following stroke onset. The study drug was to be taken 45–60 minutes before therapy, which included motor activities (mean 23.2 and 24.8 sessions in the co-careldopa and placebo groups, respectively). The mean number of investigational medicinal product doses taken was 20.6 in the co-careldopa group and 22.4 in the placebo group. Ability to walk independently was not improved at 8 weeks [40.6% (co-careldopa) vs. 44.6% (placebo); odds ratio 0.78, 95% confidence interval (CI) 0.53 to 1.15], 6 months [51.6% (co-careldopa) vs. 53.3% (placebo)] or 12 months [51.6% (co-careldopa) vs. 56.8% (placebo)]. There were no significant differences for Barthel Index, Nottingham Extended Activities of Daily Living, ABILHAND Manual Ability Measure or Modified Rankin Scale, pain or fatigue at any time point. Montreal Cognitive Assessment scores did not significantly differ; the majority of participants had cognitive impairment at baseline, which improved during 12 months’ follow-up. No difference was observed in General Health Questionnaire 12-item version scores between groups at 8 weeks and 12 months but, at 6 months, those in the co-careldopa group reported significantly better general health [mean difference (MD) –1.33, 95% CI –2.57 to –0.10]. Mortality at 12 months was not significantly different. Carers in the placebo group reported significantly greater burden at 6 months (MD 5.05, 95% CI 0.10 to 10.01) and 12 months (MD 7.52, 95% CI 1.87 to 13.18). CONCLUSION: Co-careldopa in addition to routine NHS occupational and physical therapy is not clinically effective or cost-effective in improving walking, physical functioning, mood or cognition following stroke. We recommend further research to develop imaging and clinical markers that would allow identification of promising drug therapies that would enhance motor therapy in improving walking ability and arm function. Further research is needed to compare strategies of giving drug therapy intermittently immediately prior to therapy sessions or as continuous background daily administration. LIMITATIONS: In total, 10.3% of patients were lost to follow-up at 8 weeks and < 10% of patients met the strict per-protocol definition. Despite this, the findings are robust and generalisable to patients with limited mobility in the first few weeks after stroke. TRIAL REGISTRATION: Current Controlled Trials ISRCTN99643613. FUNDING: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership

A posture and mobility training package for care home staff: results of a cluster randomised controlled feasibility trial (the PATCH trial)

Background: provision of care for care home residents with complex needs is challenging. Physiotherapy and activity interventions can improve well-being but are often time-limited and resource intensive. A sustainable approach is to enhance the confidence and skills of staff who provide care. This trial assessed the feasibility of undertaking a definitive evaluation of a posture and mobility training programme for care staff. Design and setting: a cluster randomised controlled feasibility trial with embedded process evaluation. Ten care homes in Yorkshire, United Kingdom, were randomised (1:1) to the skilful care training package (SCTP) or usual care (UC). Participants: residents who were not independently mobile. Intervention: SCTP—delivered by physiotherapists to care staff. Objectives and measurements: key objectives informed progression to a definitive trial. Recruitment, retention and intervention uptake were monitored. Data, collected by a blinded researcher, included pain, posture, mobility, hospitalisations and falls. This informed data collection feasibility and participant safety. Results: a total of 348 residents were screened; 146 were registered (71 UC, 75 SCTP). Forty two were lost by 6 months, largely due to deaths. While data collection from proxy informants was good (>95% expected data), attrition meant that data completion rates did not meet target. Data collection from residents was poor due to high levels of dementia. Intervention uptake was variable—staff attendance at all sessions ranged from 12.5 to 65.8%. There were no safety concerns. Conclusion: care home and resident recruitment are feasible, but refinement of data collection approaches and intervention delivery are needed for this trial and care home research more widely

Effectiveness of Provider and Community Interventions to Improve Treatment of Uncomplicated Malaria in Nigeria: A Cluster Randomized Controlled Trial

The World Health Organization recommends that malaria be confirmed by parasitological diagnosis before treatment using Artemisinin-based Combination Therapy (ACT). Despite this, many health workers in malaria endemic countries continue to diagnose malaria based on symptoms alone. This study evaluates interventions to help bridge this gap between guidelines and provider practice. A stratified cluster-randomized trial in 42 communities in Enugu state compared 3 scenarios: Rapid Diagnostic Tests (RDTs) with basic instruction (control); RDTs with provider training (provider arm); and RDTs with provider training plus a school-based community intervention (provider-school arm). The primary outcome was the proportion of patients treated according to guidelines, a composite indicator requiring patients to be tested for malaria and given treatment consistent with the test result. The primary outcome was evaluated among 4946 (93%) of the 5311 patients invited to participate. A total of 40 communities (12 in control, 14 per intervention arm) were included in the analysis. There was no evidence of differences between the three arms in terms of our composite indicator (p = 0.36): stratified risk difference was 14% (95% CI -8.3%, 35.8%; p = 0.26) in the provider arm and 1% (95% CI -21.1%, 22.9%; p = 0.19) in the provider-school arm, compared with control. The level of testing was low across all arms (34% in control; 48% provider arm; 37% provider-school arm; p = 0.47). Presumptive treatment of uncomplicated malaria remains an ingrained behaviour that is difficult to change. With or without extensive supporting interventions, levels of testing in this study remained critically low. Governments and researchers must continue to explore alternative ways of encouraging providers to deliver appropriate treatment and avoid the misuse of valuable medicines