"Even if the test result is negative, they should be able to tell us what is wrong with us": a qualitative study of patient expectations of rapid diagnostic tests for malaria.

BACKGROUND: The debate on rapid diagnostic tests (RDTs) for malaria has begun to shift from whether RDTs should be used, to how and under what circumstances their use can be optimized. This has increased the need for a better understanding of the complexities surrounding the role of RDTs in appropriate treatment of fever. Studies have focused on clinician practices, but few have sought to understand patient perspectives, beyond notions of acceptability. METHODS: This qualitative study aimed to explore patient and caregiver perceptions and experiences of RDTs following a trial to assess the introduction of the tests into routine clinical care at four health facilities in one district in Ghana. Six focus group discussions and one in-depth interview were carried out with those who had received an RDT with a negative test result. RESULTS: Patients had high expectations of RDTs. They welcomed the tests as aiding clinical diagnoses and as tools that could communicate their problem better than they could, verbally. However, respondents also believed the tests could identify any cause of illness, beyond malaria. Experiences of patients suggested that RDTs were adopted into an existing system where patients are both physically and intellectually removed from diagnostic processes and where clinicians retain authority that supersedes tests and their results. In this situation, patients did not feel able to articulate a demand for test-driven diagnosis. CONCLUSIONS: Improvements in communication between the health worker and patient, particularly to explain the capabilities of the test and management of RDT negative cases, may both manage patient expectations and promote patient demand for test-driven diagnoses

The impact of providing rapid diagnostic malaria tests on fever management in the private retail sector in Ghana: a cluster randomized trial

Objective: To examine the impact of providing rapid diagnostic tests for malaria on fever management in private drug retail shops where most poor rural people with fever present, with the aim of reducing current massive overdiagnosis and overtreatment of malaria. Design: Cluster randomized trial of 24 clusters of shops. Setting: Dangme West, a poor rural district of Ghana. Participants: Shops and their clients, both adults and children. Interventions: Providing rapid diagnostic tests with realistic training. Main outcome measures: The primary outcome was the proportion of clients testing negative for malaria by a double-read research blood slide who received an artemisinin combination therapy or other antimalarial. Secondary outcomes were use of antibiotics and antipyretics, and safety. Results: Of 4603 clients, 3424 (74.4%) tested negative by double-read research slides. The proportion of slide-negative clients who received any antimalarial was 590/1854 (32%) in the intervention arm and 1378/1570 (88%) in the control arm (adjusted risk ratio 0.41 (95% CI 0.29 to 0.58), P<0.0001). Treatment was in high agreement with rapid diagnostic test result. Of those who were slide-positive, 690/787 (87.8%) in the intervention arm and 347/392 (88.5%) in the control arm received an artemisinin combination therapy (adjusted risk ratio 0.96 (0.84 to 1.09)). There was no evidence of antibiotics being substituted for antimalarials. Overall, 1954/2641 (74%) clients in the intervention arm and 539/1962 (27%) in the control arm received appropriate treatment (adjusted risk ratio 2.39 (1.69 to 3.39), P<0.0001). No safety concerns were identified. Conclusions: Most patients with fever in Africa present to the private sector. In this trial, providing rapid diagnostic tests for malaria in the private drug retail sector significantly reduced dispensing of antimalarials to patients without malaria, did not reduce prescribing of antimalarials to true malaria cases, and appeared safe. Rapid diagnostic tests should be considered for the informal private drug retail sector

Accuracy of Malaria Rapid Diagnostic Tests in Community Studies and their Impact on Treatment of Malaria in an Area with Declining Malaria Burden in North-Eastern Tanzania.

Despite some problems related to accuracy and applicability of malaria rapid diagnostic tests (RDTs), they are currently the best option in areas with limited laboratory services for improving case management through parasitological diagnosis and reducing over-treatment. This study was conducted in areas with declining malaria burden to assess; 1) the accuracy of RDTs when used at different community settings, 2) the impact of using RDTs on anti-malarial dispensing by community-owned resource persons (CORPs) and 3) adherence of CORPs to treatment guidelines by providing treatment based on RDT results. Data were obtained from: 1) a longitudinal study of passive case detection of fevers using CORPs in six villages in Korogwe; and 2) cross-sectional surveys (CSS) in six villages of Korogwe and Muheza districts, north-eastern, Tanzania. Performance of RDTs was compared with microscopy as a gold standard, and factors affecting their accuracy were explored using a multivariate logistic regression model. Overall sensitivity and specificity of RDTs in the longitudinal study (of 23,793 febrile cases; 18,154 with microscopy and RDTs results) were 88.6% and 88.2%, respectively. In the CSS, the sensitivity was significantly lower (63.4%; χ2=367.7, p<0.001), while the specificity was significantly higher (94.3%; χ2=143.1, p<0.001) when compared to the longitudinal study. As determinants of sensitivity of RDTs in both studies, parasite density of<200 asexual parasites/μl was significantly associated with high risk of false negative RDTs (OR≥16.60, p<0.001), while the risk of false negative test was significantly lower among cases with fever (axillary temperature ≥37.5 °C) (OR≤0.63, p≤0.027). The risk of false positive RDT (as a determinant of specificity) was significantly higher in cases with fever compared to afebrile cases (OR≥2.40, p<0.001). Using RDTs reduced anti-malarials dispensing from 98.9% to 32.1% in cases aged ≥5 years. Although RDTs had low sensitivity and specificity, which varied widely depending on fever and parasite density, using RDTs reduced over-treatment with anti-malarials significantly. Thus, with declining malaria prevalence, RDTs will potentially identify majority of febrile cases with parasites and lead to improved management of malaria and non-malaria fevers

Comparing health workforce forecasting approaches for healthcare planning: The case for ophthalmologists

Health workforce planning is essential in the provision of quality healthcare. Several approaches to planning are customarily used and advocated, each with unique underlying assumptions. Thus, a thorough understanding of each assumption is required in order to make an informed decision on the choice of forecasting approach to be used. For illustration, we compare results for eye care requirements in Singapore using three established workforce forecasting approaches – workforce-to-population-ratio, needs based approach, utilization based approach – and a proposed robust integrated approach to discuss the appropriateness of each approach under various scenarios. Four simulation models using the systems modeling methodology of system dynamics were developed for use in each approach. These models were initialized and simulated using the example of eye care workforce planning in Singapore, to project the number of ophthalmologists required up to the year 2040 under the four different approaches. We found that each approach projects a different number of ophthalmologists required over time. The needs based approach tends to project the largest number of required ophthalmologists, followed by integrated, utilization based and workforce-to-population ratio approaches in descending order. The four different approaches vary widely in their forecasted workforce requirements and reinforce the need to be discerning of the fundamental differences of each approach in order to choose the most appropriate one. Further, health workforce planning should also be approached in a comprehensive and integrated manner that accounts for developments in demographic and healthcare systems

Subacute Oral Toxicity Assessment of Alchornea cordifolia (Schumach and Thonn) Müll Arg (Euphorbiaceae) Extract in Rats

Purpose: To assess Alchornea cordifolia, a medicinal plant with numerous biological actions and uses in traditional medicine, for possible toxicity in rats.Methods: The probable effect of the ethanol extract of Alchornea cordifolia (250 - 2000 mg/kg, p.o.) by gavage was evaluated on blood cellular elements and chemistry, as well as on the weight and histology of vital organs of male adult Spraque-Dawley rats.Results: Daily administration of the extract for two weeks did not cause significant changes in most haematological indices and blood chemistry. However, a dose-dependent increase (p &lt; 0.01) in neutrophils was observed. Relative organ weights were comparable in control and treated groups. Histopathological assessment of liver sections of treated-rats showed normal architecture at doses &lt; 1000 mg/kg. However, in animals treated with 1000 and 2000 mg/kg, cloudy swelling of hepatocytes with vacuolar and hydropic degeneration were evident. Kidney architecture at all dose levels was normal.Conclusion: The results of the study show that administration of the ethanol extract of Alchornea cordifolia to male adult rats by gavage evoked histopathologic changes in the liver at doses &gt; 1000 mg/kg. These findings call for caution in the use of Alchornea cordifolia especially in high doses.Keywords: Alchornea cordifolia, Rats, Subacute oral toxicity, Neutrophils, Hepatocytes, Hydropic denegeratio

In vitro anti-malarial interaction and gametocytocidal activity of cryptolepine

YesBackground: Discovery of novel gametocytocidal molecules is a major pharmacological strategy in the elimination and eradication of malaria. The high patronage of the aqueous root extract of the popular West African anti-malarial plant Cryptolepis sanguinolenta (Periplocaceae) in traditional and hospital settings in Ghana has directed this study investigating the gametocytocidal activity of the plant and its major alkaloid, cryptolepine. This study also investigates the anti-malarial interaction of cryptolepine with standard anti-malarials, as the search for new anti-malarial combinations continues. Methods: The resazurin-based assay was employed in evaluating the gametocytocidal properties of C. sanguinolenta and cryptolepine against the late stage (IV/V) gametocytes of Plasmodium falciparum (NF54). A fixed ratio method based on the SYBR Green I fluorescence-based assay was used to build isobolograms from a combination of cryptolepine with four standard anti-malarial drugs in vitro using the chloroquine sensitive strain 3D7. Results: Cryptolepis sanguinolenta ( IC50 = 49.65 nM) and its major alkaloid, cryptolepine ( IC50 = 1965 nM), showed high inhibitory activity against the late stage gametocytes of P. falciparum (NF54). In the interaction assays in asexual stage, cryptolepine showed an additive effect with both lumefantrine and chloroquine with mean ΣFIC50s of 1.017 ± 0.06 and 1.465 ± 0.17, respectively. Cryptolepine combination with amodiaquine at therapeutically relevant concentration ratios showed a synergistic effect (mean ΣFIC50 = 0.287 ± 0.10) whereas an antagonistic activity (mean ΣFIC50 = 4.182 ± 0.99) was seen with mefloquine. Conclusions: The findings of this study shed light on the high gametocytocidal properties of C. sanguinolenta and cryptolepine attributing their potent anti-malarial activity mainly to their effect on both the sexual and asexual stages of the parasite. Amodiaquine is a potential drug partner for cryptolepine in the development of novel fixed dose combinations

Young adults with kidney failure lived experiences of kidney replacement therapy decision‐making

Background Young adults living with kidney failure make decisions to select a kidney replacement therapy choice in partnership with healthcare professionals. However, little is known about how they experience kidney replacement therapy treatment decision-making and the impact this has on their well-being. Objectives To explore young adults living with kidney failure experiences of treatment decision-making. The treatment decision-making investigated is about the choice of dialysis and/or kidney transplant options. Design A qualitative interpretive hermeneutic phenomenology study. Participants Purposeful sampling was used to recruit young adults with kidney failure from social media, electronic media such as local kidney group websites and word of mouth. Semistructured interviews were conducted with (n = 18) participants aged 18–30 years. Approach Inductive analysis of the data were performed using Braun and Clarke's thematic analysis framework. Findings The five themes generated were (1) awareness and anticipation of future kidney replacement therapy decision; (2) health information and education; (3) engaging in decision-making, support and choices; (4) implementation of kidney replacement therapy and transitioning into the new normal life and (5) the impact of decision-making and choice on well-being. Conclusions Decision-making significantly affected young adults' psychosocial and mental well-being. Young adults had unmet informational and decisional needs and struggled to cope due to lack of support. A four-talk model, with an implement talk phase added to the existing three-talk (team talk, option talk, decision talk) shared decision-making model, would promote a focus on the implementation of choice and support the transitioning from previous life to long-term dependence on treatment