Study protocol for evaluation of aid to diagnosis for developmental dysplasia of the hip in general practice: controlled trial randomised by practice

Introduction: In the UK, a compulsory ‘6-week hip check’ is performed in primary care for the detection of developmental dysplasia of the hip (DDH). However, missed diagnoses and infants incorrectly labelled with DDH remain a problem, potentially leading to adverse consequences for infants, their families and the National Health Service. National policy states that infants should be referred to hospital if the 6-week check suggests DDH, though there is no available tool to aid examination or offer guidelines for referral. We developed standardised diagnostic criteria for DDH, based on international Delphi consensus, and a 9-item checklist that has the potential to enable non-experts to diagnose DDH in a manner approaching that of experts. / Methods and analysis: We will conduct a controlled trial randomised by practice that will compare a diagnostic aid against standard care for the hip check. The primary objective is to determine whether an aid to the diagnosis of DDH reduces the number of clinically insignificant referrals from primary care to hospital and the number of late diagnosed DDH. The trial will include a qualitative process evaluation, an assessment of professional behavioural change and a full health economic evaluation. We will recruit 152 general practitioner practices in England. These will be randomised to conduct the hip checks with use of the study diagnostic aid and/or as per usual practice. The total number of infants seen during a 15-month recruitment period will be 110 per practice. Two years after the 6-week hip check, we will measure the number of referred infants that are (1) clinically insignificant for DDH and (2) those that constitute appropriate referrals. / Ethics and dissemination: This study has approval from the Health Research Authority (16/1/2020) and the Confidentiality Advisory Group (18/2/2020). Results will be published in peer-reviewed academic journals, disseminated to patient organisations and the media. / Trial registration number: NCT04101903; Pre-results

A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear

Social sciences research in neglected tropical diseases 2: A bibliographic analysis

The official published version of the article can be found at the link below.Background There are strong arguments for social science and interdisciplinary research in the neglected tropical diseases. These diseases represent a rich and dynamic interplay between vector, host, and pathogen which occurs within social, physical and biological contexts. The overwhelming sense, however, is that neglected tropical diseases research is a biomedical endeavour largely excluding the social sciences. The purpose of this review is to provide a baseline for discussing the quantum and nature of the science that is being conducted, and the extent to which the social sciences are a part of that. Methods A bibliographic analysis was conducted of neglected tropical diseases related research papers published over the past 10 years in biomedical and social sciences. The analysis had textual and bibliometric facets, and focussed on chikungunya, dengue, visceral leishmaniasis, and onchocerciasis. Results There is substantial variation in the number of publications associated with each disease. The proportion of the research that is social science based appears remarkably consistent (<4%). A textual analysis, however, reveals a degree of misclassification by the abstracting service where a surprising proportion of the "social sciences" research was pure clinical research. Much of the social sciences research also tends to be "hand maiden" research focused on the implementation of biomedical solutions. Conclusion There is little evidence that scientists pay any attention to the complex social, cultural, biological, and environmental dynamic involved in human pathogenesis. There is little investigator driven social science and a poor presence of interdisciplinary science. The research needs more sophisticated funders and priority setters who are not beguiled by uncritical biomedical promises

Pre-referral Rectal Artesunate Treatment by Community-Based Treatment Providers in Ghana, Guinea-Bissau, Tanzania, and Uganda (Study 18): A Cluster-Randomized Trial

BACKGROUND:  If malaria patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate prior to hospital referral can prevent death and disability. The goal is to reduce death from malaria by having rectal artesunate treatment available and used. How best to do this remains unknown. METHODS:  Villages remote from a health facility were randomized to different community-based treatment providers trained to provide rectal artesunate in Ghana, Guinea-Bissau, Tanzania, and Uganda. Prereferral rectal artesunate treatment was provided in 272 villages: 109 through community-based health workers (CHWs), 112 via trained mothers (MUMs), 25 via trained traditional healers (THs), and 26 through trained community-chosen personnel (COMs); episodes eligible for rectal artesunate were established through regular household surveys of febrile illnesses recording symptoms eligible for prereferral treatment. Differences in treatment coverage with rectal artesunate in children aged <5 years in MUM vs CHW (standard-of-care) villages were assessed using the odds ratio (OR); the predictive probability of treatment was derived from a logistic regression analysis, adjusting for heterogeneity between clusters (villages) using random effects. RESULTS:  Over 19 months, 54 013 children had 102 504 febrile episodes, of which 32% (31 817 episodes) had symptoms eligible for prereferral therapy; 14% (4460) children received treatment. Episodes with altered consciousness, coma, or convulsions constituted 36.6% of all episodes in treated children. The overall OR of treatment between MUM vs CHW villages, adjusting for country, was 1.84 (95% confidence interval [CI], 1.20-2.83; P = .005). Adjusting for heterogeneity, this translated into a 1.67 higher average probability of a child being treated in MUM vs CHW villages. Referral compliance was 81% and significantly higher with CHWs vs MUMs: 87% vs 82% (risk ratio [RR], 1.1 [95% CI, 1.0-1.1]; P < .0001). There were more deaths in the TH cluster than elsewhere (RR, 2.7 [95% CI, 1.4-5.6]; P = .0040). CONCLUSIONS:  Prereferral episodes were almost one-third of all febrile episodes. More than one-third of patients treated had convulsions, altered consciousness, or coma. Mothers were effective in treating patients, and achieved higher coverage than other providers. Treatment access was low. CLINICAL TRIALS REGISTRATION:  ISRCTN58046240

Understanding caretakers' dilemma in deciding whether or not to adhere with referral advice after pre-referral treatment with rectal artesunate

BACKGROUND: Malaria kills. A single rectal dose of artesunate before referral can reduce mortality and prevent permanent disability. However, the success of this intervention depends on caretakers' adherence to referral advice for follow-up care. This paper explores the dilemma facing caretakers when they are in the process of deciding whether or not to transit their child to a health facility after pre-referral treatment with rectal artesunate. METHODS: Four focus group discussions were held in each of three purposively selected villages in Mtwara rural district of Tanzania. Data were analysed manually using latent qualitative content analysis. RESULTS: The theme "Caretakers dilemma in deciding whether or not to adhere with referral advice after pre-referral treatment with rectal artesunate" depicts the challenge they face. Caretakers' understanding of the rationale for going to hospital after treatment--when and why they should adhere--influenced adherence. Caretakers, whose children did not improve, usually adhered to referral advice. If a child had noticeably improved with pre-referral treatment however, caretakers weighed whether they should proceed to the facility, balancing the child's improved condition against other competing priorities, difficulties in reaching the health facilities, and the perceived quality of care at the health facility. Some misinterpretation were found regarding the urgency and rationale for adherence among some caretakers of children who improved which were attributed to be possibly due to their prior understanding. CONCLUSION: Some caretakers did not adhere when their children improved and some who adhered did so without understanding why they should proceed to the facility. Successful implementation of the rectal artesunate strategy depends upon effective communication regarding referral to clinic

Role of traditional healers in the management of severe malaria among children below five years of age: the case of Kilosa and Handeni Districts, Tanzania

BACKGROUND: The current malaria control strategy of WHO centres on early diagnosis and prompt treatment using effective drugs. Children with severe malaria are often brought late to health facilities and traditional health practitioners are said to be the main cause of treatment delay. In the context of the Rectal Artesunate Project in Tanzania, the role of traditional healers in the management of severe malaria in children was studied. METHODOLOGY: A community cross-sectional study was conducted in Kilosa and Handeni Districts, involving four villages selected on the basis of existing statistics on the number of traditional health practitioners involved in the management of severe malaria. A total of 41 traditional health practitioners were selected using the snowballing technique, whereby in-depth interviews were used to collect information. Eight Focus Group Discussions (FGDs) involving traditional health practitioners, caregivers and community leaders were carried out in each district. RESULTS: Home management of fever involving sponging or washing with warm water at the household level, was widely practiced by caregivers. One important finding was that traditional health practitioners and mothers were not linking the local illness termed degedege, a prominent feature in severe malaria, to biomedically-defined malaria. The majority of mothers (75%) considered degedege to be caused by evil spirits. The healing process was therefore organized in stages and failure to abide to the procedure could lead to relapse of degedege, which was believed to be caused by evil spirits. Treatment seeking was, therefore, a complex process and mothers would consult traditional health practitioners and modern health care providers, back and forth. Referrals to health facilities increased during the Rectal Artesunate Project, whereby project staff facilitated the process after traditional medical care with the provision of suppositories. This finding is challenging the common view that traditional healers are an important factor of delay for malaria treatment, they actually play a pivotal role by giving "bio-medically accepted first aid" which leads to reduction in body temperature hence increasing chances of survival for the child. Increasing the collaboration between traditional healers and modern health care providers was shown to improve the management of severe malaria in the studied areas. INTERPRETATION AND CONCLUSION: Traditional health care is not necessarily a significant impediment or a delaying factor in the treatment of severe malaria. There is a need to foster training on the management of severe cases, periodically involving both traditional health practitioners and health workers to identify modalities of better collaboration

Rectal artemisinins for malaria: a review of efficacy and safety from individual patient data in clinical studies

<p>Abstract</p> <p>Background</p> <p>Rectal administration of artemisinin derivatives has potential for early treatment for severe malaria in remote settings where injectable antimalarial therapy may not be feasible. Preparations available include artesunate, artemisinin, artemether and dihydroartemisinin. However each may have different pharmacokinetic properties and more information is needed to determine optimal dose and comparative efficacy with each another and with conventional parenteral treatments for severe malaria.</p> <p>Methods</p> <p>Individual patient data from 1167 patients in 15 clinical trials of rectal artemisinin derivative therapy (artesunate, artemisinin and artemether) were pooled in order to compare the rapidity of clearance of <it>Plasmodium falciparum </it>parasitaemia and the incidence of reported adverse events with each treatment. Data from patients who received comparator treatment (parenteral artemisinin derivative or quinine) were also included. Primary endpoints included percentage reductions in parasitaemia at 12 and 24 hours. A parasite reduction of >90% at 24 hours was defined as parasitological success.</p> <p>Results</p> <p>Artemisinin and artesunate treatment cleared parasites more rapidly than parenteral quinine during the first 24 hours of treatment. A single higher dose of rectal artesunate treatment was five times more likely to achieve >90% parasite reductions at 24 hours than were multiple lower doses of rectal artesunate, or a single lower dose administration of rectal artemether.</p> <p>Conclusion</p> <p>Artemisinin and artesunate suppositories rapidly eliminate parasites and appear to be safe. There are less data on artemether and dihydroartemisinin suppositories. The more rapid parasite clearance of single high-dose regimens suggests that achieving immediate high drug concentrations may be the optimal strategy.</p

Diversity of Plasmodium falciparum Chloroquine Resistance Transporter (pfcrt) Exon 2 Haplotypes in the Pacific from 1959 to 1979

Nearly one million deaths are attributed to malaria every year. Recent reports of multi-drug treatment failure of falciparum malaria underscore the need to understand the molecular basis of drug resistance. Multiple mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) are involved in chloroquine resistance, but the evolution of complex haplotypes is not yet well understood. Using over 4,500 archival human serum specimens collected from 19 Pacific populations between 1959 and 1979, the period including and just prior to the appearance of chloroquine treatment failure in the Pacific, we PCR-amplified and sequenced a portion of the pfcrt exon 2 from 771 P. falciparum-infected individuals to explore the spatial and temporal variation in falciparum malaria prevalence and the evolution of chloroquine resistance. In the Pacific, the prevalence of P. falciparum varied considerably across ecological zones. On the island of New Guinea, the decreases in prevalence of P. falciparum in coastal, high-transmission areas over time were contrasted by the increase in prevalence during the same period in the highlands, where transmission was intermittent. We found 78 unique pfcrt haplotypes consisting of 34 amino acid substitutions and 28 synonymous mutations. More importantly, two pfcrt mutations (N75D and K76T) implicated in chloroquine resistance were present in parasites from New Hebrides (now Vanuatu) eight years before the first report of treatment failure. Our results also revealed unexpectedly high levels of genetic diversity in pfcrt exon 2 prior to the historical chloroquine resistance selective sweep, particularly in areas where disease burden was relatively low. In the Pacific, parasite genetic isolation, as well as host acquired immune status and genetic resistance to malaria, were important contributors to the evolution of chloroquine resistance in P. falciparum

Improving pulse crops as a source of protein, starch and micronutrients

Pulse crops have been known for a long time to have beneficial nutritional profiles for human diets but have been neglected in terms of cultivation, consumption and scientific research in many parts of the world. Broad dietary shifts will be required if anthropogenic climate change is to be mitigated in the future, and pulse crops should be an important component of this change by providing an environmentally sustainable source of protein, resistant starch and micronutrients. Further enhancement of the nutritional composition of pulse crops could benefit human health, helping to alleviate micronutrient deficiencies and reduce risk of chronic diseases such as type 2 diabetes. This paper reviews current knowledge regarding the nutritional content of pea (Pisum sativum L.) and faba bean (Vicia faba L.), two major UK pulse crops, and discusses the potential for their genetic improvement