Improving healthcare quality for transgender patients in the perioperative setting: The patient's perspective.

Transgender individuals reported higher rates of discrimination and barriers to care within healthcare settings than their cisgender counterparts. There is a paucity of literature concerning the barriers experienced within perioperative healthcare settings. Participants completed a sociodemographic questionnaire and a 7-item Likert-type scale survey: the Everyday Discrimination Scale Adapted for Medical Settings. Overall, 57% of trans-individuals who underwent gender-affirming surgery reported perceptions of discrimination when interacting with healthcare providers within the perioperative setting according to responses from the Discrimination in Medical Settings Survey. There was an overall difference in the summary scores between participants based on gender transition. These findings highlight an opportunity to address barriers to care related to discrimination and negative patient-provider interactions. These findings have implications for the development and integration of patient-informed, evidence-based, trans-specific, educational and cultural competency trainings to enhance the healthcare professional's knowledge, attitudes, comfort and ability to care for the transgender population.Key phrases: Transgender individuals reported higher rates of discrimination and barriers to care; enhancing the healthcare professional's knowledge, attitudes, comfort and ability to care for the transgender population; opportunities to address barriers to care related to discrimination and negative patient-provider interactions; individuals who transitioned from male-to-female (MTF) had higher scores related to perceptions of discrimination during interactions with healthcare providers.

A Programme for Risk Assessment and Minimisation of Progressive Multifocal Leukoencephalopathy Developed for Vedolizumab Clinical Trials.

INTRODUCTION: Over the past decade, the potential for drug-associated progressive multifocal leukoencephalopathy (PML) has become an increasingly important consideration in certain drug development programmes, particularly those of immunomodulatory biologics. Whether the risk of PML with an investigational agent is proven (e.g. extrapolated from relevant experience, such as a class effect) or merely theoretical, the serious consequences of acquiring PML require careful risk minimisation and assessment. No single standard for such risk minimisation exists. Vedolizumab is a recently developed monoclonal antibody to α4ß7 integrin. Its clinical development necessitated a dedicated PML risk minimisation assessment as part of a global preapproval regulatory requirement. OBJECTIVE: The aim of this study was to describe the multiple risk minimisation elements that were incorporated in vedolizumab clinical trials in inflammatory bowel disease patients as part of the risk assessment and minimisation of PML programme for vedolizumab. METHODS: A case evaluation algorithm was developed for sequential screening and diagnostic evaluation of subjects who met criteria that indicated a clinical suspicion of PML. An Independent Adjudication Committee provided an independent, unbiased opinion regarding the likelihood of PML. RESULTS: Although no cases were detected, all suspected PML events were thoroughly reviewed and successfully adjudicated, making it unlikely that cases were missed. CONCLUSION: We suggest that this programme could serve as a model for pragmatic screening for PML during the clinical development of new drugs.

Long-term Efficacy of Vedolizumab for Crohn's Disease.

BACKGROUND AND AIMS: Vedolizumab is a gut-selective α4ß7 integrin antagonist therapy for ulcerative colitis and Crohn's disease. The GEMINI long-term safety [LTS] trial is an ongoing open-label study investigating the safety of vedolizumab. We present interim exploratory analyses of efficacy in patients with Crohn's disease. METHODS: Patients from the C13004, GEMINI 2 and GEMINI 3 studies and vedolizumab-naïve patients could enrol in GEMINI LTS and received vedolizumab every 4 weeks. Data were collected from May 22, 2009 to June 27, 2013. Outcomes of clinical response and remission, defined by the Harvey-Bradshaw Index, and health-related quality of life [HRQL] were assessed for up to 152 weeks of treatment in the efficacy population. RESULTS: Among patients with response at week 6 in GEMINI 2 who received vedolizumab continuously, 83% [n=100/120] and 89% [n=62/70] of patients with available data were in remission after 104 and 152 weeks, respectively. Increased dosing frequency from every 8 weeks [GEMINI 2] to every 4 weeks [GEMINI LTS] improved outcomes in patients who had withdrawn early from GEMINI 2, with 47% [n=27/57] experiencing clinical response and 32% [n=18/57] in remission at week 52 of GEMINI LTS [up from 39% and 4% before the dose increase]. Similar improvements were observed regardless of prior tumour necrosis factor [TNF] antagonist exposure. Long-term benefits of HRQL were also observed. CONCLUSIONS: The clinical benefits of vedolizumab continued with long-term treatment regardless of prior TNF antagonist exposure. Increased dosing frequency might improve outcomes in patients who lose response to conventional 8-weekly dosing.

Long-term Efficacy of Vedolizumab for Ulcerative Colitis.

BACKGROUND AND AIMS: The GEMINI long-term safety [LTS] study is a continuing phase 3 trial investigating the safety and efficacy of vedolizumab, an α4ß7 integrin antagonist for ulcerative colitis [UC] and Crohn's disease. We provide an interim analysis of efficacy in patients with UC. METHODS: Patients from the C13004 and GEMINI 1 studies and a cohort of vedolizumab-naïve patients received open-label vedolizumab every 4 weeks. Interim data were collected from May 22, 2009 to June 27, 2013. Clinical response and remission, evaluated using partial Mayo scores, and health-related quality of life [HRQL] were assessed for up to 152 weeks of cumulative treatment in the efficacy population. RESULTS: As of June 27, 2013, 63% of the efficacy population [n = 532/845] were continuing treatment. Among patients who responded to vedolizumab induction and had data available, 88% [n = 120/136] were in remission after 104 weeks of exposure (96% [n = 70/73] after 152 weeks). Among patients who withdrew from every-8-week vedolizumab maintenance in GEMINI 1 [n = 32] before week 52, increased dosing to every 4 weeks in GEMINI LTS resulted in response and remission rates of 41% and 28%, respectively, after 52 weeks, an increase from 19% and 6%, respectively, from before the dose increase. Similar benefits were demonstrated regardless of prior tumour necrosis factor-antagonist exposure. Durable benefits on HRQL were also observed. CONCLUSIONS: Patients with UC experienced clinical and HRQL improvements with continued vedolizumab treatment. Increased dosing frequency to every 4 weeks was beneficial in patients who had loss of response to 8-weekly dosing.

Occurrence of adverse events among patients with inflammatory bowel disease in the HealthCore Integrated Research Database.

OBJECTIVES: Inflammatory bowel disease (IBD) is a chronic condition commonly requiring lifelong care. Both IBD and IBD-related treatments can cause significant morbidity, and it is often difficult to differentiate their relative etiologic contribution to adverse events (AEs). The objectives of this study were to assess the rates of select AEs among patients with IBD as a function of disease severity and of the use of anti-tumor necrosis factor alpha (anti-TNFα) medications. METHODS: We conducted a retrospective cohort study of IBD patients in the HealthCore Integrated Research Database (HIRD(TM)) between January 2004 and January 2011 to determine rates of AEs in patients with mild and moderate to severe IBD. Key study endpoints were select prespecified malignant neoplasms, infections, and other AEs of interest. RESULTS: A total of 33,386 IBD patients (52.7% ulcerative colitis; 47.3% Crohn's disease) met the inclusion criteria, and 60% had been followed for ≥1 year. Patients with moderate to severe IBD had increased rates of infections, lymphatic and digestive tract cancers, gastrointestinal (GI) perforations, and myocardial infarctions versus patients with mild IBD. Patients with IBD who used anti-TNFα therapies during the study had increased incidence of many types of infections, certain GI cancers (including rectal and anal cancer), intestinal perforations, and kidney stones compared with patients who had never used anti-TNFα therapies. CONCLUSIONS: Results from this large US cohort provide descriptive information on AE rates in a population of IBD patients undergoing routine care, estimating background incidence rates of AEs that are not readily available in the published literature. Our study findings may be limited owing to a lack of generalizability and potential for misclassification due to reliance on medical diagnosis and treatment and procedure codes to identify disease, comorbidities, and treatments. Further research and validation of our findings in other populations and databases are needed.

The epidemiology and targeted therapies for relapsed and refractory CD30+ lymphomas.

BACKGROUND: Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL) both have consistent expression of CD30, a cytokine receptor that is expressed by activated T and B cells but is largely absent from normal tissue. METHODS: A literature search was conducted via PubMed, Google Scholar, and UpToDate to identify relevant peer-reviewed original research or review articles on HL, sALCL, and CD30 targeted therapies. RESULTS: These lymphomas are both more common among males, young adults and the elderly. Although many patients with HL and sALCL can achieve long-term remission after standard first-line therapy, up to a third of these patients are refractory to or relapse after initial therapy. Among these relapsed/refractory patients, many experience disease progression and/or death despite subsequent treatment, and treatment-related adverse events and mortality are not uncommon. To address the need for safer and more effective therapies for these relapsed/refractory patients, researchers have developed therapies that specifically target CD30-expressing cells. Brentuximab vedotin, an antibody-drug conjugate that selectively delivers a toxic microtubule-disrupting agent to malignant cells with CD30 expression, is the first such therapy to be approved in the US and Europe. In clinical trials, brentuximab vedotin has demonstrated efficacy and safety in patients with HL after failure of autologous stem cell transplantation (ASCT), or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and in patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. CONCLUSION: HL and sALCL are both CD30+ lymphomas, and therapies like brentuximab vedotin that target cells expressing CD30 hold promise for the treatment of these diseases.