301 research outputs found
Ethics, economics, and the use of primaquine to reduce falciparum malaria transmission in asymptomatic populations.
No full textYoel Lubell and colleagues consider ethical and economic perspectives on mass drug administration of primaquine to limit transmission of P. falciparum malaria. Please see later in the article for the Editors' Summary
Guidelines for the standardized collection of predictor variables in studies for pediatric sepsis (guidelines)~Pediatric Sepsis Predictors Standardization (PS2) Working Group
No full textThese guidelines aim to maximize the efficiency of data-sharing collaborations in pediatric sepsis research by facilitating the standardization of data collection in predictors captured in future studies
C-reactive protein testing to discriminate bacterial from viral pathogens among febrile patients in Southeast Asia and its impact on antibiotic prescribing in primary care
No full textIn an era marked by the worldwide decline of malaria, fever remains the most frequent reason for seeking health care in the tropics. Non-malarial pathogens are mainly studied among hospitalised patients, while evidence in primary care is scarce. In addition to the limited evidence on the local epidemiology, prescribers routinely face difficulty in identifying patients who really need an antibiotic. This translates into high antibiotic prescription, fuelling the worldwide spread of antimicrobial resistance. C-reactive protein (CRP) is one of the most studied host-response biomarkers for guiding the management of acutely febrile patients, although evidence mainly originates from hospitals in high-income countries, implying that findings may not be applicable in primary care in low-to-middle-income countries (LMICs). My thesis aims to explore the bacteria and viruses driving acute fever in primary care in Southeast Asia, as well as the potential utility of CRP in identifying patients who need an antibiotic. To this end, we designed an individually randomised controlled trial of CRP-guided treatment in all febrile children and adults, ‘the CRP Study’. We also collected blood and respiratory specimens to ascertain the causes of fever in these patients. We found a significant antibiotic reduction of 7.8 percentage-points using CRP at a 40 mg/L threshold compared to routine practice, without differences in clinical outcome. Routine prescription levels were lower than prior to study implementation, suggesting that future studies should adopt a cluster rather than individual randomised design. Influenza virus type A, dengue virus and respiratory syncytial virus were the key pathogens among our primary care patients, although ascertaining causality was challenging due to lack of acontrol group, especially in nasopharyngeal swabs. Most bacterial infections showed low inflammatory levels and recovered without antibiotics, questioning the interpretation of microbiological findings among non-severe patients. CRP performance in distinguishing bacterial from viral pathogens was limited, suggesting that CRP may rather discriminate self-limiting from serious infections. We also evaluated the performance of CRP in a cohort of febrile patients in Tanzania. Here CRP showed a high sensitivity for detecting bacterial bloodstream infection, indicating that prospective evaluations on its effect on antibiotic prescriptions could be envisaged. The detection of bacterial zoonotic pathogens was of lower accuracy, warranting further evaluations for various levels of healthcare settings and age categories
Enhanced decision models for the diagnosis and treatment of malaria in an age of ACTs
No full textNew diagnostics and treatments for malaria have renewed hope in the developing world
as they promise relief from the debilitating effects of this illness. Accompanying these
interventions are a growing number of economic evaluations assessing their efficiency. To
ensure the relevance of economic evaluations to decision making purposes it is imperative
that they use best available computational and statistical approaches.
This thesis initially discusses the necessary requirements for economic evaluations to
ensure they provide appropriate decision recommendations. This is followed by four
evaluations of malaria diagnostics and treatments using methods new to the context of
malaria.
The first study expands the range of factors included in the evaluation of diagnostic tests,
addressing compromised adherence to test results and societal costs associated with
antimalarial use.
The second analysis demonstrates how models can be designed as decision support tools
allowing stakeholders to enter local data along with other parameter estimates, priorities
and values. Both Bayesian and deterministic models are presented for comparison.
The third analysis demonstrates the use of multilevel models for economic evaluations
based on multi-centre trials. The chapter compares the results of a multilevel model
evaluating treatments for severe malaria with those obtained in a standard analysis.
The fourth study uses a Markov model to evaluate the efficiency of Home Management of
Malaria programmes. The use of a Markov model addresses the restricted portrayal of
malaria infection and illness that has characterised many previous evaluations.
In addition to contributing to a better understanding of the cost-effectiveness of the latest
malaria treatments and diagnostic tests, this thesis seeks to bridge the growing gap
between recent methodological advances in the field of economic evaluation, and the
relative paucity of evaluations producing practical and effective policy recommendations
for areas of the world where the burden of malaria and other diseases is heaviest
Priority-setting for malaria control and elimination in Myanmar
No full textIn Myanmar, Plasmodium falciparum malaria is important because of both the burden of disease and the emergence of parasites resistant to artemisinin-based therapies. In 2012, concomitant with the lifting of international economic sanctions, funding for malaria control and elimination in Myanmar rose significantly. The University of Oxford was asked to support priority setting by assessing the relative cost-effectiveness of insecticide- treated bed nets and community health workers, particularly with respect to planning in the Myanmar Artemisinin Resistance Containment region along the east of the country. In the context of rising artemisinin resistance and, later, the goal of regional malaria elimination by 2030, reduction in malaria transmission was an important consideration in prioritising between interventions.
A cost-effectiveness analysis was undertaken using both a static decision tree model and a dynamic disease transmission model. Supporting work towards this analysis included a systematic review of dynamic-transmission economic-evaluations and the creation of a data repository to collate governmental and non-governmental malaria case records. In addition, initially unplanned work on economic evaluation methodology was completed; identifying challenges in the application of cost utility analysis to this decision problem and proposing a framework for budget-based geographic resource allocation as an adaptation of standard methods.
The results of this work include a tripling of the number of malaria diagnostic reports available between 2012 and 2014 (71% increase in Plasmodium falciparum cases) with this data showing a decrease in Plasmodium falciparum cases over time, alongside rising testing rates. Cost utility analysis found that, in general, malaria community health workers are more costly yet more effective than insecticide treated bed nets, though in both cases cost effectiveness is very much context dependent. Geographic allocation analyses using both static and dynamic models illustrate the potential for economic evaluation to provide both more detailed and more practical policy recommendations. Parameter uncertainty was explored in both cases. Some township recommendations were robust to both parameter uncertainty and model variation (structural uncertainty). Viewed through the lens of the Reference Case for Economic Evaluation in Low and Middle Income Countries (published during the course of this DPhil), budget-based geographic resource allocation largely adheres to the healthcare economic evaluation principles and offers improvements to dealing with heterogeneity and resource constraints. This DPhil recommends that Myanmar malaria policy is tailored to reflect geographic variation in intervention cost-effectiveness, rather than focusing on universal coverage, and illustrates a framework for economic evaluation to support budget-based geographic allocation.</p
Application of economic analysis to evaluate various infectious diseases in Vietnam
No full textThis thesis is composed of two economic evaluations: one trial-based study and one model-based study. In a recent study published in Clinical Infectious Diseases in 2011, a team of OUCRU investigators found that immediate antiretroviral therapy (ART) was not associated with improved 9-month survival in HIV-associated TBM patients (HR, 1.12; 95% CI, .81 toâ1.55; P = .50). An economic evaluation of this clinical trial was conducted to examine the cost-effectiveness of immediate ART (initiate ART within 1 week of study entry) versus deferred ART (initiate ART after 2 months of TB treatment) in HIV-associated TBM patients. Over 9 months, immediate ART was not different from deferred ART in terms of costs and QALYs gained. Late initiation of ART during TB and HIV treatment for HIV-positive TBM patients proved to be the most cost-effective strategy.
Increasing resistance of Plasmodium falciparum malaria to artemisinin is posing a major threat to the global effort to eliminate malaria. Artesmisinin combination therapies (ACT) are currently known as the most efficacious first-line therapies to treat uncomplicated malaria. However, resistance to both artemisinin and partner drugs is developing and this could result in increasing morbidity, mortality, and economic costs. One strategy advocated for delaying the development of resistance to the ACTs is the wide-scale deployment of multiple first-line therapies. A previous modeling study examined that the use of multiple first-line therapies (MFT) reduced the long-term treatment failures compared with strategies in which a single first-line ACT was recommended. Motivated by observed results of the published modelling study in the Lancet, the cost-effectiveness of the MFT versus the single first-line therapies was assessed in settings of different transmission intensities, treatment coverages and fitness cost of resistance using a previously developed model of the dynamics of malaria and a literature âbased cost estimate of changing antimalarial drug policy at national level. This study demonstrates that the MFT strategies outperform the single first-line strategies in terms of costs and benefits across the wide range of epidemiological and economic scenarios considered. The second analysis of the thesis is not only internationally relevant but also with a focus towards healthcare practice in Vietnam.
These two studies add significant new cost-effectiveness evidence in Vietnam. This thesis presents the first trial-based economic evaluation in Vietnam considers patient-health outcome measures as the participants have cognitive limitations (tuberculous meningitis), dealing with missing data along with the potential ways to handle this common problem by the use of multiple imputation, and the issues of censored costs data. Having identified these issues would support the decision makers or stakeholders including the pharmaceutical industry to devise a new guideline on how to implement a well-design trial-based economic evaluation in Vietnam in the future. Another novelty of this thesis is the introduction of the detailed of costing of drug regimens change in which the economic evaluations considering the drug policy change often do not include. This cost could be substantial to the healthcare system for retraining the staff and publishing the new guidelines. This thesis will document the costs incurred by the Vietnamese government by changing the first-line treatment of malaria, from single first-line therapy (ACT) to multiple first-line therapies.</p
The epidemiology of acute febrile illness in rural South and Southeast Asian primary care, and evaluation of selected interventions to improve its management
No full textAcute febrile illness (AFI) accounts for a major proportion of presentations in primary care, particularly in tropical low-income and middle-income countries (LMICs). The paradigm that tropical AFI is primarily attributable to malaria is no longer valid in South and Southeast Asia, yet there is precious little high-quality contemporary evidence on its epidemiology, especially in the rural, resource-constrained, and under-studied areas containing most of the regional population. Clinical and health policy decision-making is, thus, hampered leading to larger-scale problems such as antimicrobial over-prescription and development of resistance, and hospital overcrowding from poorly-targeted referrals. Viewing this pressing but neglected problem through a pragmatic, multi-disciplinary lens, this thesis aims to lay the foundations for the development of interventions to improve primary care management of AFI in rural South and Southeast Asia at both individual patient and population levels. Beginning with two multi-national prospective studies embedded in the South and Southeast Asian Community-based Trials Network Rural Febrile Illness project, it details the baseline contextual and epidemiological realities confronting health workers and policymakers in Bangladesh, Cambodia, Laos, Myanmar, and Thailand daily, which have thus far been poorly researched. The first showed that while there were considerable differences between these sites, all relied on primary health centres and village health/malaria workers as the main providers of primary healthcare. The key results from the second, an observational study, were that in the 82,760 patients enrolled by these two provider groups the most frequent diagnoses were upper respiratory tract infection (URTI, 61.0%) and fever of unclear source (30.7%). This study also showed that targeting of antibiotic prescriptions and identification of patients with potentially severe illness could be improved, although mortality was very low (0.01%). Building on the results, a variety of research methodologies based on real-world data were used to generate evidence on potential interventions, starting with one commonly used in high-income settings (pulse oximetry), followed by one for which the need is well-established but data for its development is lacking (a multiplex rapid diagnostic test for AFI). With regard to pulse oximetry, a systematic review concluded that it may assist clinicians in diagnosing and managing paediatric pneumonia, but for the greatest impact on patient outcomes should be implemented as part of a health systems approach. For the latter, the most important finding from a priority-setting Delphi survey was that it should be able to diagnose dengue and enteric fever at a minimum in adults and children. Health economic modelling studies showed that both these interventions were likely to be cost-effective in the settings which they were evaluated. The culminating work describes the development of a novel algorithmic electronic clinical decision support tool which integrates epidemiological and clinical data to guide diagnosis and management, and the methodology for its evaluation via a cluster-randomised trial in Cambodia. The generalisability of the knowledge gained from this thesis to other tropical LMICs, as well as the barriers to its application and implementation, are also discussed, along with potential solutions
CRP-PCT-BMC.dta
No full textProcalcitonin and CRP values from well characterised samples from fever studies in Southeast Asia<br
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