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Ingram J.R.,Institute of Infection and Immunity | Abbott R.,University of Wales | Ghazavi M.,Nottingham Treatment Center | Alexandroff A.B.,University of Leicester | And 3 more authors.
British Journal of Dermatology | Year: 2014

Background Hidradenitis suppurativa (HS) has been neglected by medical researchers and society in general, despite being a relatively common, painful, chronic skin disease. Objectives To generate a top 10 list of HS research priorities, from the perspectives of patients with HS, carers and clinicians, to take to funding bodies. Methods A priority setting partnership was established between patients with HS, carers and clinicians, following the James Lind Alliance process. Survey 1 requested submission of HS uncertainties, which were grouped into 'indicative uncertainties' for prioritization in survey 2. The 30 highest-ranked indicative uncertainties were reduced to a 'top 10' list using nominal group technique at a prioritization workshop attended by all relevant HS stakeholders. Results In total 1495 potential uncertainties were submitted in survey 1, including 57% from patients with HS and carers, and grouped into 55 indicative uncertainties. Ranking in survey 2 was completed by 371 participants, 50% of whom were patients and carers. The final workshop was attended by 22 HS stakeholders and four facilitators and produced a top 10 list, the three highest priorities in descending order being (i) What is the most effective and safe group of oral treatments in treating HS? (ii) What is the best management of an acute flare? (iii)What is the impact of HS and its treatment on people with HS? Conclusions The top 10 HS research priorities have been directly disseminated to funders to raise awareness of HS. The next step is to generate research questions that will provide the evidence needed to improve care for patients with HS. What's already known about this topic? Hidradenitis suppurativa (HS) has been relatively neglected by society and medical research funding bodies, resulting in a lack of evidence to guide HS care. Obtaining research funding for HS is challenging. Priority setting partnerships can be used to raise awareness of a condition and demonstrate to funders and researchers the priorities of both patients and clinicians. What does this study add? Using transparent and inclusive James Lind Alliance methodology, a top 10 list of HS research priorities was identified, from the perspective of people with HS, their carers and the clinicians involved in their care. This process is important because of the large number of HS uncertainties that exist, and it will help researchers and medical funding bodies to decide which HS projects should be prioritized. © 2014 British Association of Dermatologists.

Ahmed Z.,Institute of Infection and Immunity | Kawamura T.,Yamanashi University | Shimada S.,Yamanashi University | Piguet V.,Institute of Infection and Immunity
Journal of Investigative Dermatology | Year: 2015

Dendritic cells (DCs) and their subsets have multifaceted roles in the early stages of HIV-1 transmission and infection. DC studies have led to remarkable discoveries, including identification of restriction factors, cellular structures promoting viral transmission including the infectious synapse or the interplay of the C-type lectins, Langerin on Langerhans cells (LCs), and dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin on other DC subsets, limiting or facilitating HIV transmission to CD4 + T cells, respectively. LCs/DCs are also exposed to encountering HIV-1 and other sexually transmitted infections (herpes simplex virus-2, bacteria, fungi), which reprogram HIV-1 interaction with these cells. This review will summarize advances in the role of DCs during HIV-1 infection and discuss their potential involvement in the development of preventive strategies against HIV-1 and other sexually transmitted infections. © 2015 The Society for Investigative Dermatology. © 2015 The Society for Investigative Dermatology.

Krishna S.,Institute of Infection and Immunity | Ganapathi S.,St George's, University of London | Ster I.C.,Institute of Infection and Immunity | Saeed M.E.M.,Johannes Gutenberg University Mainz | And 7 more authors.
EBioMedicine | Year: 2015

Background: Artesunate is an antimalarial agent with broad anti-cancer activity in in vitro and animal experiments and case reports. Artesunate has not been studied in rigorous clinical trials for anticancer effects. Aim: To determine the anticancer effect and tolerability of oral artesunate in colorectal cancer (CRC). Methods: This was a single centre, randomised, double-blind, placebo-controlled trial. Patients planned for curative resection of biopsy confirmed single primary site CRC were randomised (n. =. 23) by computer-generated code supplied in opaque envelopes to receive preoperatively either 14 daily doses of oral artesunate (200. mg; n. =. 12) or placebo (n. =. 11). The primary outcome measure was the proportion of tumour cells undergoing apoptosis (significant if >. 7% showed Tunel staining). Secondary immunohistochemical outcomes assessed these tumour markers: VEGF, EGFR, c-MYC, CD31, Ki67 and p53, and clinical responses. Findings: 20 patients (artesunate. =. 9, placebo. =. 11) completed the trial per protocol. Randomization groups were comparable clinically and for tumour characteristics. Apoptosis in >. 7% of cells was seen in 67% and 55% of patients in artesunate and placebo groups, respectively. Using Bayesian analysis, the probabilities of an artesunate treatment effect reducing Ki67 and increasing CD31 expression were 0.89 and 0.79, respectively. During a median follow up of 42. months 1 patient in the artesunate and 6 patients in the placebo group developed recurrent CRC. Interpretation: Artesunate has anti-proliferative properties in CRC and is generally well tolerated. © 2014.

PubMed | Johannes Gutenberg University Mainz, Institute of Tropical Medicine, Abel Salazar Biomedical Sciences Institute and Institute of Infection and Immunity
Type: | Journal: Pharmacological research | Year: 2016

Schistosomiasis is a helminthic disease affecting more than 200 million people in the tropics as well as returning travellers. Treatment mainly relies on a single drug, praziquantel. Praziquantel cannot kill developing schistosomula resulting in frequent treatment failures and re-infections. Monotherapy also favors the selection for resistance. New drugs are therefore urgently needed. The activity of the semi-synthetic artemisinin derivatives artemether, artesunate and arteether is not restricted to malaria. We reviewed their anti-schistosomal activity in vivo and in patients by searching the PubMed database for publications since 1983 with the search terms artemisinin and Schistosoma. Reports on in vivo studies in animals and clinical trials in human beings were selected. S. mansoni, S. japonicum, and S. haematobium have been tested in mice, rabbits, hamsters, and dogs. These artemisinin derivatives strongly reduced total worm rates with stronger reduction rates for female worms than for males. The drugs also reduced egg burden and egg-caused granulomata in the host liver. Artemisinin-type drugs induced oxidative and metabolic stress leading to morphological damage and decreased fertility of the parasites. Although artemether and artesunate have been investigated in numerous clinical trials, the poor quality of many has led to inconsistent results and has not provided convincing evidence on the therapeutic value against schistosomiasis. Despite these methodological concerns, clinical trials may indicate anti-schistosomal activity in patients. Convincing clinical trials providing unambiguous evidence are now needed. Furthermore, suitable treatment protocols for combination therapy to prevent/treat praziquantel-resistant Schistosoma strains should be investigated.

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