Generating new evidence,improving clinical practice and developing research capacity: the benefits of recruiting to the U.K. Dermatology Clinical Trials Network's STOP GAP and BLISTER trials

Clinical trials may benefit clinical practice in three ways: firstly, clinicians may change their practice according to the new trial evidence; secondly, clinical processes can improve when working on a trial; and thirdly, research capacity is increased. We held a meeting to present and discuss the results of two large multicentre randomized controlled trials delivered through the U.K. Dermatology Clinical Trials Network. Investigators gave reflections on how the trials had changed their clinical practice. The STOP GAP trial showed that prednisolone and ciclosporin are equally effective as first‐line systemic treatment for pyoderma gangrenosum. The final decision of which treatment to use should be based on the different adverse event profiles of the two drugs in relation to comorbidities, along with age, disease severity and patient preference. The BLISTER trial showed that starting people with pemphigoid on doxycycline produces acceptable short‐term effectiveness and a superior safety profile to oral corticosteroids. Recruiting to these trials has led to the development of new specialist clinics with improved documentation. It has increased the profile of participating departments and embedded research in the department's activities. Helping to design and run these trials has also allowed trial staff to develop new skills in research design, which has been beneficial for career development. These and other benefits of recruiting to the trials are summarized here. We hope that these reflections will inspire wider involvement in clinical research.     

Palliative or Hospice Care? Understanding the Similarities and Differences

With advances in health care and medical technology, the focus of medical care has been on curing. As people live longer, the possibility of experiencing chronic and life‐limiting disease not only increases but also spurs the ethical question “Is length of life or quality of life most important?” Palliative care may be confused with hospice care, as both focus on symptom management and improved quality of life for those with chronic life‐limiting disease. A better understanding of each healthcare option is needed for appropriate and timely patient referral. The purpose of this article is to identify the similarities and differences between these two options, clarify when referral is appropriate for hospice or palliative care services, and discuss the nurse's role in caring for patients with chronic disease.     

Physical Frailty Phenotype and the Development of Geriatric Syndromes in Older Adults with Coronary Heart Disease

BackgroundFrailty, a clinical state of vulnerability, is associated with subsequent adverse geriatric syndromes in the general population. We examined the long-term impact of frailty on geriatric outcomes among older patients with coronary heart disease.MethodsWe used the National Health and Aging Trends Study, a prospective cohort study linked to a Medicare sample. Coronary heart disease was identified by self-report or International Classification of Diseases (ICD) codes 1-year prior to the baseline visit. Frailty was measured using the Fried physical frailty phenotype. Geriatric outcomes were assessed annually during a 6-year follow-up.ResultsOf the 4656 participants, 1213 (26%) had a history of coronary heart disease 1-year prior to their baseline visit. Compared to those without frailty, subjects with frailty were older (ages ≥75: 80.9% vs 68.9%, P < 0.001), more likely to be female, and belong to an ethnic minority. The prevalence of hypertension, stroke, falls, disability, anxiety/depression, and multimorbidity were much higher in the frail, than nonfrail, participants. In a discrete time survival model, the incidence of geriatric syndromes during 6-year follow-up including 1) dementia, 2) loss of independence, 3) activities of daily living disability, 4) instrumental activities of daily living disability, and 5) mobility disability were significantly higher in the frail than in the nonfrail older patients with coronary heart disease.ConclusionIn patients with coronary heart disease, frailty is a risk factor for the accelerated development of geriatric outcomes. Efforts to identify frailty in the context of coronary heart disease are needed, as well as interventions to limit or reverse frailty status for older patients with coronary heart disease.     

Controlled trial of maintenance cimetidine treatment in healed duodenal ulcer: short and long-term effects.

Forty-two patients with endoscopically diagnosed duodenal ulcer were studied in a double-blind trial after their ulcers had been healed with cimetidine. Cimetidine was effective in preventing relapse, only five of the 20 patients allocated to cimetidine 400 mg twice daily relapsing during the six months' treatment, compared with 16 of the 22 on placebo treatment (P less than 0.01). Cimetidine was safe in the dosage and duration used, no symptomatic, haematological, or biochemical abnormalities occurring during the trial. Subsequent follow-up at the end of the trial when treatment had been stopped showed that relapse was frequent, particularly in the cimetidine group, making the cumulative relapse rate eight months after completion of the trial similar in the two groups (75% in the cimetidine group, 86% in the placebo group). It seems likely that maintenance cimetidine treatment has to be continued indefinitely in patients with duodenal ulcer, and, until such treatment is shown to be safe and effective, surgical treatment remains a logical option for many patients.     

Hyperbaric oxygen therapy improves angiogenesis and bone formation in critical sized diaphyseal defects

Besides the use of autologous bone grafting several osteoconductive and osteoinductive methods have been reported to improve bone healing. However, persistent non‐union occurs in a considerable number of cases and compromised angiogenesis is suspected to impede bone regeneration. Hyperbaric oxygen therapy (HBO) improves angiogenesis. This study evaluates the effects of HBO on bone defects treated with autologous bone grafting in a bone defect model in rabbits. Twenty‐four New‐Zealand White Rabbits were subjected to a unilateral critical sized diaphyseal radius bone defect and treated with autologous cancellous bone transplantation. The study groups were exposed to an additional HBO treatment regimen. Bone regeneration was evaluated radiologically and histologically at 3 and 6 weeks, angiogenesis was assessed by immunohistochemistry at three and six weeks. The additional administration of HBO resulted in a significantly increased new bone formation and angiogenesis compared to the sole treatment with autologous bone grafting. These results were apparent after three and six weeks of treatment. The addition of HBO therapy to autologous bone grafts leads to significantly improved bone regeneration. The increase in angiogenesis observed could play a crucial role for the results observed. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:513–520, 2015.     

Cytotoxic T lymphocyte precursor (CTL-p) frequency analysis in unrelated donor bone marrow transplantation: two case studies

HLA 'matched' unrelated donor bone marrow transplantation (BMT) is associated with an increased incidence and severity of acute graft-versus-host disease (GVHD) in comparison with HLA-identical sibling transplants. Using a limiting dilution analysis system for quantitating frequencies of alloreactive cytotoxic T lymphocyte precursors (CTL-p), we previously demonstrated a correlation between CTL-p frequency and HLA disparity between responder and stimulator, and between CTL-p frequency and the incidence of acute GVHD following HLA A, B, DR matched unrelated donor BMT. In this study we assayed CTL-p frequencies in two HLA 'matched' unrelated donor/patient pairs, with single HLA antigenic mismatches detected by allogenotyping or isoelectric focusing but not by HLA serology, and demonstrated that the CTL-ps were specifically directed at the mismatched antigen. Both class I and class II antigens were detected. These data, and our previous work, suggest that high CTL-p frequencies in HLA 'matched' unrelated pairs are indicative of HLA antigenic variants undetected by serology but recognized by molecular typing, and that these are responsible for the value of the assay in predicting acute GVHD after BMT. We propose that this assay system be used in aiding final donor selection before unrelated or mismatched related donor BMT.