Early VEGF testing in inflammatory neuropathy avoids POEMS syndrome misdiagnosis and associated costs

BACKGROUND: Prompt diagnosis and early treatment prevents disability in Polyneuropathy Organomegaly Endocrinopathy Monoclonal-protein and Skin Changes (POEMS) syndrome. Delay in diagnosis is common with 55% of patients initially incorrectly diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Patients are often treated with intravenous immunoglobulin which is both expensive and ineffective in the treatment of POEMS. Testing patients with acquired demyelinating neuropathy with serum vascular endothelial growth factor (VEGF) more accurately identifies POEMS syndrome than the current standard of care. Incorporating VEGF testing into screening could prevent misdiagnosis and reduce costs. METHODS: We used observed treatment information for patients in the University College London Hospital's POEMS syndrome database (n=100) and from the National Immunoglobulin Database to estimate costs associated with incorrect CIDP diagnoses across our cohort. We conducted a model-based cost-effectiveness analysis to compare the current diagnostic algorithm with an alternative which includes VEGF testing for all patients with an acquired demyelinating neuropathy. RESULTS: Treatment associated with an incorrect CIDP diagnosis led to total wasted healthcare expenditures of between £808 550 and £1 111 756 across our cohort, with an average cost-per-POEMS-patient misdiagnosed of £14 701 to £20 214. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy would lead to annual cost-savings of £107 398 for the National Health Service and could prevent misdiagnosis in 16 cases per annum. CONCLUSIONS: Misdiagnosis in POEMS syndrome results in diagnostic delay, disease progression and significant healthcare costs. Introducing mandatory VEGF testing for patients with acquired demyelinating neuropathy is a cost-effective strategy allowing for early POEMS diagnosis and potentially enabling prompt disease-directed therapy

The costs of accessible quality assured syphilis diagnostics: informing quality systems for rapid syphilis tests in a Tanzanian setting.

OBJECTIVES: To determine the costs of Rapid Syphilis Test (RSTs) as compared with rapid plasma reagin (RPR) when implemented in a Tanzanian setting, and to determine the relative impact of a quality assurance (QA) system on the cost of RST implementation. METHODS: The incremental costs for RPR and RST screening programmes in existing antenatal care settings in Geita District, Tanzania were collected for 9 months in subsequent years from nine health facilities that varied in size, remoteness and scope of antenatal services. The costs per woman tested and treated were estimated for each facility. A sensitivity analysis was constructed to determine the impact of parameter and model uncertainty. FINDINGS: In surveyed facilities, a total of 6362 women were tested with RSTs compared with 224 tested with RPR. The range of unit costs was $1.76-$3.13 per woman screened and $12.88-$32.67 per woman treated. Unit costs for the QA system came to $0.51 per woman tested, of which 50% were attributed to salaries and transport for project personnel. CONCLUSIONS: Our results suggest that rapid syphilis diagnostics are very inexpensive in this setting and can overcome some critical barriers to ensuring universal access to syphilis testing and treatment. The additional costs for implementation of a quality system were found to be relatively small, and could be reduced through alterations to the programme design. Given the potential for a quality system to improve quality of diagnosis and care, we recommend that QA activities be incorporated into RST roll-out

Using Choice Experiments to Improve Equity in Access to Socially Marketed HIV Prevention Products

Designing strategies to introduce new HIV prevention technologies requires balancing equitable access with sustainable distribution, particularly in resource constrained settings with high HIV prevalence. This paper explores how knowledge of preference heterogeneity can guide the equitable targeting of HIV prevention products using differentiated advertising and product placement to balance increased access with sustainability. A discrete choice experiment elicited 1016 women's preferences for distribution of HIV prevention products in South Africa. Qualitative research guided the experimental design which considered distribution outlet, collection method, advertising message, and price. A range of choice models, including random parameters logit, latent class and latent class random parameters logit models, were compared for fit. A latent class model showed the best fit and distinguished two classes of women: Class 1 were significantly more likely to be cohabiting and unemployed, who preferred products advertised for HIV prevention distributed through clinics and were highly price sensitive. Class 2 significantly preferred distribution through pharmacies and advertising around women's empowerment, while price was not a key factor. This analysis suggests that equity in access to new products could be advanced through exploiting preference heterogeneity between groups. The identified groups can be then used to design social marketing differentiated distribution strategies. Distributing free products promoted for HIV prevention could discourage ‘leakage’ of highly subsidised products to women with some capacity to pay, while priced products marketed for women's empowerment through pharmacies could encourage cost recovery with minimal reductions in coverage among employed women

Optimising the management of vaginal discharge syndrome in Bulgaria: cost effectiveness of four clinical algorithms with risk assessment

OBJECTIVES: To evaluate the performance and cost effectiveness of the WHO recommendations of incorporating risk-assessment scores and population prevalence of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) into vaginal discharge syndrome (VDS) algorithms. METHODS: Non-pregnant women presenting with VDS were recruited at a non-governmental sexual health clinic in Sofia, Bulgaria. NG and CT were diagnosed by PCR and vaginal infections by microscopy. Risk factors for NG/CT were identified in multivariable analysis. Four algorithms based on different combinations of behavioural factors, clinical findings and vaginal microscopy were developed. Performance of each algorithm was evaluated for detecting vaginal and cervical infections separately. Cost effectiveness was based on cost per patient treated and cost per case correctly treated. Sensitivity analysis explored the influence of NG/CT prevalence on cost effectiveness. RESULTS: 60% (252/420) of women had genital infections, with 9.5% (40/423) having NG/CT. Factors associated with NG/CT included new and multiple sexual partners in the past 3 months, symptomatic partner, childlessness and >or=10 polymorphonuclear cells per field on vaginal microscopy. For NG/CT detection, the algorithm that relied solely on behavioural risk factors was less sensitive but more specific than those that included speculum examination or microscopy but had higher correct-treatment rate and lower over-treatment rates. The cost per true case treated using a combination of risk factors, speculum examination and microscopy was euro 24.08. A halving and tripling of NG/CT prevalence would have approximately the inverse impact on the cost-effectiveness estimates. CONCLUSIONS: Management of NG/CT in Bulgaria was improved by the use of a syndromic approach that included risk scores. Approaches that did not rely on microscopy lost sensitivity but were more cost effective

Informing targeted HIV self-testing: a protocol for discrete choice experiments in Malawi, Zambia and Zimbabwe

Introduction HIV self-testing (HIVST) is a new approach to HIV testing where a person collects his or her own specimen, performs an HIV test and interprets the result, either alone or with someone he or she trusts. It is becoming increasingly relevant as a complement to standard-of-care HIV testing and is now recommended by the World Health Organization. Few studies have explored user preferences around HIVST service delivery and optimal models for increasing uptake and linkage to care, particularly among hard-to-reach populations. This paper describes an ongoing study that uses discrete choice experiments (DCE) to identify key HIVST service characteristics that drive people’s willingness to self-test for HIV and link to care, measure the relative strength of user preferences, and explore preference heterogeneity in Southern Africa. Method and Analysis Two DCEs – one on HIVST delivery and one on linkage to care after a positive self-test – are being administered in Malawi, Zambia and Zimbabwe. The designs in each country were informed by a qualitative study, which identified key HIVST service characteristics that influence user decision-making and refined scenario presentations and illustrations. Following data collection, DCE data will be analysed using a multinomial logit model as well as latent class, nested logit and generalised mixed models to examine heterogeneity in preferences by sociodemographic background, HIV testing experience and sexual behaviour. Ethics and dissemination The study has been approved by the College of Medicine Research Ethics Committee in Malawi, the Biomedical Ethics Committee of the University of Zambia, the Medical Research Council of Zimbabwe and the Research Ethics Committee of the London School of Hygiene and Tropical Medicine. Findings from the study will be presented at international conferences and in peer-reviewed journals. The results will help inform the HIVST implementation strategy in Southern Africa, particularly among populations underserved by standard-of-care services, such as men and young women

Challenges of using modelling evidence in the visceral leishmaniasis elimination programme in India.

As India comes closer to the elimination of visceral leishmaniasis (VL) as a public health problem, surveillance efforts and elimination targets must be continuously revised and strengthened. Mathematical modelling is a compelling research discipline for informing policy and programme design in its capacity to project incidence across space and time, the likelihood of achieving benchmarks, and the impact of different interventions. To gauge the extent to which modelling informs policy in India, this qualitative analysis explores how and whether policy makers understand, value, and reference recently produced VL modelling research. Sixteen semi-structured interviews were carried out with both users- and producers- of VL modelling research, guided by a knowledge utilisation framework grounded in knowledge translation theory. Participants reported that barriers to knowledge utilisation include 1) scepticism that models accurately reflect transmission dynamics, 2) failure of modellers to apply their analyses to specific programme operations, and 3) lack of accountability in the process of translating knowledge to policy. Political trust and support are needed to translate knowledge into programme activities, and employment of a communication intermediary may be a necessary approach to improve this process

Introduction of syphilis point-of-care tests, from pilot study to national programme implementation in Zambia: A qualitative study of healthcare workers' perspectives on testing, training and quality assurance

Syphilis affects 1.4 million pregnant women globally each year. Maternal syphilis causes congenital syphilis in over half of affected pregnancies, leading to early foetal loss, pregnancy complications, stillbirth and neonatal death. Syphilis is under-diagnosed in pregnant women. Point-of-care rapid syphilis tests (RST) allow for same-day treatment and address logistical barriers to testing encountered with standard Rapid Plasma Reagin testing. Recent literature emphasises successful introduction of new health technologies requires healthcare worker (HCW) acceptance, effective training, quality monitoring and robust health systems. Following a successful pilot, the Zambian Ministry of Health (MoH) adopted RST into policy, integrating them into prevention of mother-to-child transmission of HIV clinics in four underserved Zambian districts. We compare HCW experiences, including challenges encountered in scaling up from a highly supported NGO-led pilot to a large-scale MoH-led national programme. Questionnaires were administered through structured interviews of 16 HCWs in two pilot districts and 24 HCWs in two different rollout districts. Supplementary data were gathered via stakeholder interviews, clinic registers and supervisory visits. Using a conceptual framework adapted from health technology literature, we explored RST acceptance and usability. Quantitative data were analysed using descriptive statistics. Key themes in qualitative data were explored using template analysis. Overall, HCWs accepted RST as learnable, suitable, effective tools to improve antenatal services, which were usable in diverse clinical settings. Changes in training, supervision and quality monitoring models between pilot and rollout may have influenced rollout HCW acceptance and compromised testing quality. While quality monitoring was integrated into national policy and training, implementation was limited during rollout despite financial support and mentorship. We illustrate that new health technology pilot research can rapidly translate into policy change and scale-up. However, training, supervision and quality assurance models should be reviewed and strengthened as rollout of the Zambian RST programme continues. © 2015, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

Costs and outcomes of active and passive case detection for visceral leishmaniasis (Kala-Azar) to inform elimination strategies in Bihar, India.

BACKGROUND: Effective case identification strategies are fundamental to capturing the remaining visceral leishmaniasis (VL) cases in India. To inform government strategies to reach and sustain elimination benchmarks, this study presents costs of active- and passive- case detection (ACD and PCD) strategies used in India's most VL-endemic state, Bihar, with a focus on programme outcomes stratified by district-level incidence. METHODS: Expenditure analysis was complemented by onsite micro-costing to compare the cost of PCD in hospitals alongside index case-based ACD and a combination of blanket (house-to-house) and camp ACD from January to December 2018. From the provider's perspective, a cost analysis evaluated the overall programme cost of each activity, the cost per case detected, and the cost of scaling up ACD. RESULTS: During 2018, index case-based ACD, blanket and camp ACD, and PCD reported 1,497, 131, and 1,983 VL-positive cases at a unit cost of $522.81,$4,186.81, and $246.79, respectively. In high endemic districts, more VL cases were identified through PCD while in meso- and low-endemic districts more cases were identified through ACD. The cost of scaling up ACD to identify 3,000 additional cases ranged from$1.6-4 million, depending on the extent to which blanket and camp ACD was relied upon. CONCLUSION: Cost per VL test conducted (rather than VL-positive case identified) may be a better metric estimating unit costs to scale up ACD in Bihar. As more VL cases were identified in meso-and low-endemic districts through ACD than PCD, health authorities in India should consider bolstering ACD in these areas. Blanket and camp ACD identified fewer cases at a higher unit cost than index case-based ACD. However, the value of detecting additional VL cases early outweighs long-term costs for reaching and sustaining VL elimination benchmarks in India