Setting health research priorities using the CHNRI method: VII. a review of the first 50 applications of the CHNRI method

Background: Several recent reviews of the methods used to set research priorities have identified the CHNRI method (acronym derived from the Child Health and Nutrition Research Initiative ) as an approach that clearly became popular and widely used over the past decade. In this paper we review the first 50 examples of application of the CHNRI method, published between 2007 and 2016, and summarize the most important messages that emerged from those experiences.Methods: We conducted a literature review to identify the first 50 examples of application of the CHNRI method in chronological order. We searched Google Scholar, PubMed and so-called grey literature.Results: Initially, between 2007 and 2011, the CHNRI method was mainly used for setting research priorities to address global child health issues, although the first cases of application outside this field (eg, mental health, disabilities and zoonoses) were also recorded. Since 2012 the CHNRI method was used more widely, expanding into the topics such as adolescent health, dementia, national health policy and education. The majority of the exercises were focused on issues that were only relevant to low- and middle-income countries, and national-level applications are on the rise. The first CHNRI-based articles adhered to the five recommended priority-setting criteria, but by 2016 more than two-thirds of all conducted exercises departed from recommendations, modifying the CHNRI method to suit each particular exercise. This was done not only by changing the number of criteria used, but also by introducing some entirely new criteria (eg, low cost , sustainability , acceptability , feasibility , relevance and others).Conclusions: The popularity of the CHNRI method in setting health research priorities can be attributed to several key conceptual advances that have addressed common concerns. The method is systematic in nature, offering an acceptable framework for handling many research questions. It is also transparent and replicable, because it clearly defines the context and priority-setting criteria. It is democratic, as it relies on crowd-sourcing . It is inclusive, fostering ownership of the results by ensuring that various groups invest in the process. It is very flexible and adjustable to many different contexts and needs. Finally, it is simple and relatively inexpensive to conduct, which we believe is one of the main reasons for its uptake by many groups globally, particularly those in low- and middle-income countries

European College of Equine Internal Medicine consensus statement on equine flaviviridae infections in Europe

Horses and other equids can be infected with several viruses of the family Flaviviridae, belonging to the genus Flavivirus and Hepacivirus. This consensus statement focuses on viruses with known occurrence in Europe, with the objective to summarize the current literature and formulate clinically relevant evidence-based recommendations regarding clinical disease, diagnosis, treatment, and prevention. The viruses circulating in Europe include West Nile virus, tick-borne encephalitis virus, Usutu virus, Louping ill virus and the equine hepacivirus. West Nile virus and Usutu virus are mosquito-borne, while tick-borne encephalitis virus and Louping ill virus are tick-borne. The natural route of transmission for equine hepacivirus remains speculative. West Nile virus and tick-borne encephalitis virus can induce encephalitis in infected horses. In the British Isle, rare equine cases of encephalitis associated with Louping ill virus are reported. In contrast, equine hepacivirus infections are associated with mild acute hepatitis and possibly chronic hepatitis. Diagnosis of flavivirus infections is made primarily by serology, although cross-reactivity occurs. Virus neutralization testing is considered the gold standard to differentiate between flavivirus infections in horses. Hepacivirus infection is detected by serum or liver RT-PCR. No direct antiviral treatment against flavi- or hepacivirus infections in horses is currently available and thus, treatment is supportive. Three vaccines against West Nile virus are licensed in the European Union. Geographic expansion of flaviviruses pathogenic for equids should always be considered a realistic threat, and it would be beneficial if their detection was included in surveillance programs

South-Africa (Goodstart III) trial: community-based maternal and newborn care economic analysis

In light of South Africa’s generalized HIV/AIDS epidemic coupled with high infant mortality, we undertook a cluster Randomized Control Trial (2008–10) assessing the effect of Community Health Worker (CHW) antenatal and postnatal home visits on, amongst other indicators, levels of HIV-free survival, and exclusive and appropriate infant feeding at 12 weeks. Cost and time implications were calculated, by assessing the 15 participating CHWs, using financial records, mHealth and interviews. Sustainability and scalability were assessed, enabling identification of health system issues. The majority (96%) of women in the community received an average of 4.1 visits (target seven). The paid, single purpose CHWs spent 13 h/week on the programme. The financial cost per mother amounted to $94 ($23 per home visit). Modelling target coverage (95% mothers, seven visits) and increased efficiency showed that if CHWs spent 25h/week on the programme, the number of CHWs required would decrease from 15 to 12. The intervention almost doubled exclusive breastfeeding (EBF) at 12 weeks and showed a 6% relative increase in EBF with each additional CHW visit. Home visit programmes improve access and prevention but are not an inexpensive alternative: the observed cost per home visit is twice that of a clinic visit and in target/efficiency scenario decreases to 70% of the cost of a clinic visit. Ensuring sustainability requires optimizing the design of programmes and deployment of human resources, whilst maintaining impact. However, low remuneration of CHWs leads to shorter working hours, low motivation and sub-optimal coverage even in a situation with well-resourced supervision. The communitybased care programme in South-Africa is based on multi-purpose CHWs, its cost and impact should be compared with results from this study. Quality of support for multi-purpose CHWs may be the biggest challenge to address to achieving higher efficiency of community-based services.IBSS, ISI & Scopu

An effectiveness study of an integrated, community-based package for maternal, newborn, child and HIV care in South Africa: study protocol for a randomized controlled trial

BACKGROUND: Progress towards MDG4 in South Africa will depend largely on scaling up effective prevention against mother to child transmission (PMTCT) of HIV and also addressing neonatal mortality. This imperative drives increasing focus on the neonatal period and particularly on the development and testing of appropriate models of sustainable, community-based care in South Africa in order to reach the poor. A number of key implementation gaps affecting progress have been identified. Implementation gaps for HIV prevention in neonates; implementation gaps for neonatal care especially home postnatal care; and implementation gaps for maternal mental health support. We have developed and are evaluating and costing an integrated and scaleable home visit package delivered by community health workers targeting pregnant and postnatal women and their newborns to provide essential maternal/newborn care as well as interventions for Prevention of Mother to Child Transmission (PMTCT) of HIV. METHODS: The trial is a cluster randomized controlled trial that is being implemented in Umlazi which is a peri-urban settlement with a total population of 1 million close to Durban in KwaZulu Natal, South Africa. The trial consists of 30 randomized clusters (15 in each arm). A baseline survey established the homogeneity of clusters and neither stratification nor matching was performed. Sample size was based on increasing HIV-free survival from 74% to 84%, and calculated to be 120 pregnant women per cluster. Primary outcomes are higher levels of HIV free survival and levels of exclusive and appropriate infant feeding at 12 weeks postnatally. The intervention is home based with community health workers delivering two antenatal visits, a postnatal visit within 48 hours of birth, and a further four visits during the first two months of the infants life. We are undertaking programmatic and cost effectiveness analysis to cost the intervention. DISCUSSION: The question is not merely to develop an efficacious package but also to identify and test delivery strategies that enable scaling up, which requires effectiveness studies in a health systems context, adapting and testing Asian community-based studies in various African contexts

Setting health research priorities using the CHNRI method: VII. A review of the first 50 applications of the CHNRI method

BACKGROUND: Several recent reviews of the methods used to set research priorities have identified the CHNRI method (acronym derived from the "Child Health and Nutrition Research Initiative") as an approach that clearly became popular and widely used over the past decade. In this paper we review the first 50 examples of application of the CHNRI method, published between 2007 and 2016, and summarize the most important messages that emerged from those experiences. METHODS: We conducted a literature review to identify the first 50 examples of application of the CHNRI method in chronological order. We searched Google Scholar, PubMed and so-called grey literature. RESULTS: Initially, between 2007 and 2011, the CHNRI method was mainly used for setting research priorities to address global child health issues, although the first cases of application outside this field (eg, mental health, disabilities and zoonoses) were also recorded. Since 2012 the CHNRI method was used more widely, expanding into the topics such as adolescent health, dementia, national health policy and education. The majority of the exercises were focused on issues that were only relevant to low- and middle-income countries, and national-level applications are on the rise. The first CHNRI-based articles adhered to the five recommended priority-setting criteria, but by 2016 more than two-thirds of all conducted exercises departed from recommendations, modifying the CHNRI method to suit each particular exercise. This was done not only by changing the number of criteria used, but also by introducing some entirely new criteria (eg, "low cost", "sustainability", "acceptability", "feasibility", "relevance" and others). CONCLUSIONS: The popularity of the CHNRI method in setting health research priorities can be attributed to several key conceptual advances that have addressed common concerns. The method is systematic in nature, offering an acceptable framework for handling many research questions. It is also transparent and replicable, because it clearly defines the context and priority-setting criteria. It is democratic, as it relies on "crowd-sourcing". It is inclusive, fostering "ownership" of the results by ensuring that various groups invest in the process. It is very flexible and adjustable to many different contexts and needs. Finally, it is simple and relatively inexpensive to conduct, which we believe is one of the main reasons for its uptake by many groups globally, particularly those in low- and middle-income countries

Setting Priorities in Global Child Health Research Investments: Assessment of Principles and Practice

Članak daje pregled teoretskih i praktičnih pristupa postavljanju prioriteta prilikom ulaganja u istraživanje dječjega globalnog zdravlja. Daje i pregled prijašnjih pokušaja razvitka odgovarajućih alata i postupaka u području ulaganja u istraživanja o zdravlju. Napravljen je kratak pregled najvažnijih teoretskih postavki prema kojima bi se trebalo ravnati u postupku određivanja prioriteta. On je pokazao da će se različiti pristupi u postavljanju prioriteta, poput medicinskoga, gospodarskoga, zakonskoga, etičkoga, društvenoga, političkoga, pragmatičnoga, filozofskoga, onoga od poslodavaca i svih drugih nužno sukobiti. Posebno smo raspravili aktualne pravce istraživanja u području globalnoga dječjega zdravlja i njihov odnos prema Milenijskom cilju br. 4 organizacije Ujedinjenih naroda (UN), koji je da se između 1990. i 2015. dječja smrtnost smanji za dvije trećine. Procijenjena su postignuća pristupa koji su bili ranije primjenjivani i prikazane njihove prednosti i mane. Navedeni su razlozi organizacije Inicijativa za dječje zdravlje i prehranu (engl., Child Health and Nutrition Research Initiative) za stvaranje nove metodologije određivanja prioriteta u ulaganju u zdravstvena istraživanja i navedeni su razlozi za njezinu primjenu u području globalnoga dječjega zdravlja. Da bi se mogli obuhvatiti svi kutovi iz kojih je moguće promatrati prioritete ulaganja u istraživanja zdravlja nuždan je interdisciplinarni pristup. Određivanje prioriteta traži da njihovo stvaranje bude javno, jasno i sustavno i da u obzir uzme mnogobrojna gledišta i nastavi se na prednosti prethodnih pristupa.This article reviews theoretical and practical approaches to priority setting in global child health research investments. It also provides an overview of previous attempts to develop appropriate tools and methodologies to define priorities in health research investments. A brief review of the most important theoretical concepts that should govern priority setting processes is undertaken, showing how different perspectives, such as medical, economical, legal, ethical, social, political, rational, philosophical, stakeholder driven, and others will necessarily conflict each other in determining priorities. We specially address present research agenda in glo

Viral testing of 10 cases of Theiler's disease and 37 in-contact horses in the absence of equine biologic product administration: A prospective study (2014-2018)

Background A novel equine parvovirus (EqPV-H) was recently discovered in the equine liver with Theiler's disease. Objectives To determine the prevalence of EqPV-H infection in naturally occurring Theiler's disease cases and in-contact horses in the absence of historical equine biologic product administration. Animals Ten cases of Theiler's disease from 6 separate properties were included in the study, based on the criteria of acute onset of clinical signs of liver failure with laboratory or histopathologic findings characteristic of Theiler's disease and no history of receiving an equine biologic product within the preceding 4 months. In addition, 37 in-contact horses from 4 of the 6 properties were screened for EqPV-H infection and hepatitis. Methods In prospective case series, cases were diagnosed with Theiler's disease by the attending veterinarian and were tested for EqPV-H by PCR of liver or serum. In-contact horses were assessed via serum chemistry and PCR at the attending veterinarian's discretion. Hepatitis was defined as serum gamma-glutamyltransferase activity above reference interval. The association of EqPV-H with hepatitis was determined by Fisher's exact test. Results Nine of 10 (90%) Theiler's disease cases and 54% of tested in-contact horses were EqPV-H positive. Hepatitis was significantly associated with EqPV-H infection (P = .036). Conclusions and Clinical Importance Although further study is required to identify EqPV-H as the causative agent of Theiler's disease, EqPV-H appears strongly associated with cases of fatal Theiler's disease and subclinical hepatitis in horses in contact with those cases. The prevalence of EqPV-H infection on affected properties can be high

Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmenting thrombosis risk. Current long-term therapies to prevent arterial occlusion in diabetes are focussed on anti-platelet agents, a strategy that fails to address the contribution of coagulation proteins to the enhanced thrombotic milieu. Moreover, antiplatelet treatment is associated with bleeding complications, particularly with newer agents and more aggressive combination therapies, questioning the safety of this approach. Therefore, to safely control thrombosis risk in diabetes, an alternative approach is required with the fibrin network representing a credible therapeutic target. In the current review, we address diabetes-specific mechanistic pathways responsible for hypofibrinolysis including the role of clot structure, defects in the fibrinolytic system and increased incorporation of anti-fibrinolytic proteins into the clot. Future anti-thrombotic therapeutic options are discussed with special emphasis on the potential advantages of modulating incorporation of the anti-fibrinolytic proteins into fibrin networks. This latter approach carries theoretical advantages, including specificity for diabetes, ability to target a particular protein with a possible favourable risk of bleeding. The development of alternative treatment strategies to better control residual thrombosis risk in diabetes will help to reduce vascular events, which remain the main cause of mortality in this condition

World Health Organization and knowledge translation in maternal, newborn, child and adolescent health and nutrition.

The World Health Organization (WHO) has a mandate to promote maternal and child health and welfare through support to governments in the form of technical assistance, standards, epidemiological and statistical services, promoting teaching and training of healthcare professionals and providing direct aid in emergencies. The Strategic and Technical Advisory Group of Experts (STAGE) for maternal, newborn, child and adolescent health and nutrition (MNCAHN) was established in 2020 to advise the Director-General of WHO on issues relating to MNCAHN. STAGE comprises individuals from multiple low-income and middle-income and high-income countries, has representatives from many professional disciplines and with diverse experience and interests.Progress in MNCAHN requires improvements in quality of services, equity of access and the evolution of services as technical guidance, community needs and epidemiology changes. Knowledge translation of WHO guidance and other guidelines is an important part of this. Countries need effective and responsive structures for adaptation and implementation of evidence-based interventions, strategies to improve guideline uptake, education and training and mechanisms to monitor quality and safety. This paper summarises STAGE's recommendations on how to improve knowledge translation in MNCAHN. They include support for national and regional technical advisory groups and subnational committees that coordinate maternal and child health; support for national plans for MNCAHN and their implementation and monitoring; the production of a small number of consolidated MNCAHN guidelines to promote integrated and holistic care; education and quality improvement strategies to support guidelines uptake; monitoring of gaps in knowledge translation and operational research in MNCAHN

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies