Celiac Disease: Current and Investigational Therapies and the Role of the Pharmacist

Celiac disease is a genetically-linked autoimmune disease which affects the gastrointestinal tract. It is an inflammatory reaction to ingested gluten-containing substances that produces the most frequent symptoms of abdominal pain, bloating and intermittent or chronic diarrhea. Diagnosis can be made by blood testing for specific IgA autoantibodies and a confirmation duodenal biopsy to look for the characteristic scalloping and villous atrophy that occurs in response to the inflammation. A gluten-free diet, until recently, was the only treatment available and continues to be the mainstay of treatment. Newer adjunct therapies to dietary management include larazotide acetate, peptidases, the use of parasite Necator americanus, a desensitizing vaccine, polymeric binders, cytokine antagonists, tissue transglutaminase inhibitors, probiotics and anti-inflammatory therapy. This review will outline the potential of each of these therapies and discuss the role of the pharmacist in assisting patients with Celiac disease

Crohn\u27s Disease: Management, Emerging Therapies and the Role of the Pharmacist

Crohn\u27s disease is a relapsing-remitting disorder of the gastrointestinal tract caused by a mixture of genetic and environmental factors. Pharmacologic treatment of Crohn\u27s disease is patient-specific, and regimens vary widely between individuals. Drug regimens are typically based on 5-aminosalicylate therapy and may include a combination of steroids, histamine 2 receptor antagonists, proton pump inhibitors, immunomodulators, antibiotics, biologic agents and other medications aimed at symptom relief. A new medication, vedolizumab, is currently in phase III clinical trials awaiting U.S. Food and Drug Administration (FDA) approval for use in Crohn\u27s disease. Vedolizumab is an alpha-integrin inhibitor, which is anticipated to have a better safety profile than Tysabri® ( natalizumab ), an alpha-integrin inhibitor already approved for treatment of Crohn\u27s disease. Pharmacists have an opportunity to educate Crohn\u27s disease patients about nonpharmacologic management including counseling on diet, exercise, stress-relief therapy and use of multivitamins as well as the importance of regular colonoscopies and visits to a primary care practitioner. Pharmacists can also educate patients and practitioners about alternative therapies including probiotics, fecal microbiota transplantation and fish oils which may help manage the disease

“The most lonely condition I can imagine”: Psychosocial impacts of endometriosis on women’s identity"

Endometriosis is a condition which affects around 1-2 % of women worldwide and has profound effects on their everyday lives. Previous research has tended to focus on physical symptoms (such as chronic pain); how women manage changes to their identity and relationships as a result of endometriosis has received less attention. This paper discusses qualitative data examining how women negotiate changes to identity while living with endometriosis, in a social context where women are expected to minimise their symptoms and conform to feminine role expectations. We conducted thematic analysis of 34 replies to an online survey seeking qualitative text responses. The women identified disruptions to personal identity as a result of living with endometriosis. They talked about not feeling like themselves (Theme 1) and about reactions from medical and social connections prompting feelings that they were going “mad” (Theme 2). Participants also expressed feeling as though they were a burden to loved ones (Theme 3) which often resulted in self-silencing (Theme 4). Findings are discussed in the context of Western expectations of women’s roles in social relationships and suggest that professionals who support women with endometriosis should be aware of strategies such as self-silencing which may reduce effective self-care

“So many women suffer in silence”: A thematic analysis of women’s written accounts of coping with endometriosis

Objective: To understand women’s experiences of coping with endometriosis, and impact on their lives. Design: Women accessed an online questionnaire through a UK-based endometriosis charity website. Methods: Thirty-four women, aged 22-56 years, with self-reported medically-diagnosed endometriosis, 30 of whom were White, responded to open-ended questions, analysed using inductive thematic analysis. Results: Participants spoke about their lives being a constant struggle, where they tried to maintain their personal and working lives whilst dealing with long-term pain. Women had to “battle” for an accurate diagnosis, and had limited faith in health professionals. Coping strategies included avoidance of social events to conserve energy (self-pacing), and avoiding taking painkillers to retain alertness. Women did not feel able to be honest with family and friends about their symptoms, and felt socially isolated and misunderstood. Conclusions: Implications for health professionals are discussed, including the need for earlier diagnosis and taking women’s symptoms more seriously at referral; understanding the need to conserve energy in the context of long-term pain; that not taking pain medication may be an active choice to retain alertness; and that avoiding being honest with friends and family and subsequent feelings of isolation may be common experiences relevant to designing treatment programmes

Patients’ experiences of emergency hospital care following self-harm: Systematic review and thematic synthesis of qualitative research

Rates of hospital presentation for self-harm have increased in recent years and although clinical practice guidelines on clinical provision prioritise positive patient experiences, the quality of provision remains variable. This systematic review provides an updated and extended synthesis of qualitative research on: i) patients’ experiences of treatment following presentation to hospital; and ii) patients’ perceptions of the impact of treatment on recurrent self-harm and/or suicidal ideation, and future help-seeking. 26 studies were identified for inclusion in the final synthesis. Three meta-themes emerged: i) individuals undertake extensive identity work when presenting with self-harm, navigating the process of becoming a patient and negotiating the type of patient they want to be; ii) care ranges from gentle to hostile, with care at admission and discharge being particularly disorientating and iii) negative experiences of clinical treatment may increase future self-harm. Emerging research gaps include the need for further theoretically-informed qualitative research in this area

The G-protein-coupled receptor CLR is upregulated in an autocrine loop with adrenomedullin in clear cell renal cell carcinoma and associated with poor prognosis

Purpose: The G-protein-coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) and its ligand peptide adrenomedullin (encoded by ADM gene) are implicated in tumor angiogenesis in mouse models but poorly defined in human cancers. We therefore investigated the diagnostic/prognostic use for CLR in human tumor types that may rely on adrenomedullin signaling and in clear cell renal cell carcinoma (RCC), a highly vascular tumor, in particular. Experimental Design: In silico gene expression mRNA profiling microarray study (n = 168 tumors) and cancer profiling cDNA array hybridization (n=241 pairs of patient-matched tumor/normal tissue samples) were carried out to analyze ADM mRNA expression in 13 tumor types. Immunohistochemistry on tissue microarrays containing patient-matched renal tumor/normal tissues (n = 87 pairs) was conducted to study CLR expression and its association with clinicopathologic parameters and disease outcome. Results: ADM expression was significantly upregulated only in RCC and endometrial adenocarcinoma compared with normal tissue counterparts (P < 0.01). CLR was localized in tumor cells and vessels in RCC and upregulated as compared with patient-matched normal control kidney (P < 0.001). Higher CLR expression was found in advanced stages (P < 0.05), correlated with high tumor grade (P < 0.01) and conferred shorter overall survival (P < 0.01). Conclusions: In human tissues ADM expression is upregulated in cancer type-specific manner, implicating potential role for adrenomedullin signaling in particular in RCC, where CLR localization suggests autocrine/paracrine mode for adrenomedullin action within the tumor microenvironment. Our findings reveal previously unrecognized CLR upregulation in an autocrine loop with adrenomedullin in RCCwith potential application for this GPCR as a target for future functional studies and drug development. © 2013 AACR

Risk factors for race-day fatality in flat racing Thoroughbreds in Great Britain (2000 to 2013)

A key focus of the racing industry is to reduce the number of race-day events where horses die suddenly or are euthanased due to catastrophic injury. The objective of this study was therefore to determine risk factors for race-day fatalities in Thoroughbred racehorses, using a cohort of all horses participating in flat racing in Great Britain between 2000 and 2013. Horse-, race- and course-level data were collected and combined with all race-day fatalities, recorded by racecourse veterinarians in a central database. Associations between exposure variables and fatality were assessed using logistic regression analyses for (1) all starts in the dataset and (2) starts made on turf surfaces only. There were 806,764 starts in total, of which 548,571 were on turf surfaces. A total of 610 fatalities were recorded; 377 (61.8%) on turf. In both regression models, increased firmness of the going, increasing racing distance, increasing average horse performance, first year of racing and wearing eye cover for the first time all increased the odds of fatality. Generally, the odds of fatality also increased with increasing horse age whereas increasing number of previous starts reduced fatality odds. In the ‘all starts’ model, horses racing in an auction race were at 1.46 (95% confidence interval (CI) 1.06–2.01) times the odds of fatality compared with horses not racing in this race type. In the turf starts model, horses racing in Group 1 races were at 3.19 (95% CI 1.71–5.93) times the odds of fatality compared with horses not racing in this race type. Identification of novel risk factors including wearing eye cover and race type will help to inform strategies to further reduce the rate of fatality in flat racing horses, enhancing horse and jockey welfare and safety

Mapping the evidence about what works to safely reduce the entry of children and young people into statutory care: a systematic scoping review protocol

Introduction The increasing number of children and young people entering statutory care in the UK is a significant social, health and educational priority. Development of effective approaches to safely reduce this number remains a complex but critical issue. Despite a proliferation in interventions, evidence summaries are limited. The present protocol outlines a scoping review of research evidence to identify what works in safely reducing the number of children and young people (aged ≤18 years) entering statutory social care. The mapping of evidence gaps, clusters and uncertainties will inform the research programme of the newly funded Department for Education’s What Works Centre for Children’s Social Care. Methods and analysis The review uses Arksey and O’Malley’s scoping review methodology. Electronic database and website searches will identify studies targeting reduction of care entry, reduction of care re-entry and increase in post-care reunification. Supplementary searching techniques will include international expert consultation. Abstracts and full-text studies will be independently screened by two reviewers. Ten per cent of data abstraction will be independently conducted by two reviewers, with the remainder being extracted and then verified by a second reviewer. Descriptive numerical summaries and a thematic qualitative synthesis will be generated. Evidence will be synthesised according to primary outcome, intervention point (mapped across socioecological domains) and the realist EMMIE categorisation of evidence type (Effectiveness; Mechanisms of change; Moderators; Implementation; Economic evaluation). Ethics and dissemination Outputs will be a conceptual evidence map, a descriptive table quantitatively summarising evidence and a qualitative narrative summary. Results will be disseminated through a peer-reviewed publication, conference presentations, the What Works Centre website, and knowledge translation events with policy-makers and practitioners. Findings will inform the primary research programme of the What Works Centre for Children’s Social Care and the subsequent suite of systematic reviews to be conducted by the Centre in this substantive area