Subepithelial autoimmune bullous dermatoses disease activity assessment and therapy.

Subepidermal (subepithelial) autoimmune blistering dermatoses are a group of rare skin disorders characterized by the disruption of the dermal-epidermal junction through the action of autoantibodies. The fourth article in this continuing medical education series presents the current validated disease activity scoring systems, serologic parameters, treatments, and clinical trials for bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, bullous systemic lupus erythematosus, anti-p200 pemphigoid, linear IgA bullous dermatosis, and dermatitis herpetiformis.

Intraepithelial autoimmune bullous dermatoses disease activity assessment and therapy.

Intraepithelial autoimmune blistering dermatoses are a rare group of skin disorders characterized by disruptions of inter-keratinocyte connections within the epidermis through the action of autoantibodies. The second article in this continuing medical education series presents validated disease activity scoring systems, serologic parameters of disease, treatments, and clinical trials for pemphigus and its subtypes.

Effects of Irritable Bowel Syndrome on Daily Activities Vary Among Subtypes Based on Results From the IBS in America Survey.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is associated with significant disease burden and decreased quality of life (QOL). We investigated the effects of IBS on different areas of daily function and compared these among disease subtypes. METHODS: The Life with IBS survey was conducted by Gfk Public Affairs & Corporate Communications from September through October 2015. Respondents met Rome III criteria for constipation-predominant or diarrhea-predominant IBS (IBS-C and IBS-D, respectively). Data were collected from 3254 individuals (mean age, 47 years; 81% female; and 90% Caucasian) who met IBS criteria. RESULTS: Respondents who were employed or in school (n = 1885) reported that IBS symptoms affected their productivity an average of 8.0 days out of the month and they missed approximately 1.5 days of work/school per month because of IBS. More than half the individuals reported that their symptoms were very bothersome. Individuals with IBS-C were more likely than with IBS-D to report avoiding sex, difficulty concentrating, and feeling self-conscious. Individuals with IBS-D reported more avoidance of places without bathrooms, difficulty making plans, avoiding leaving the house, and reluctance to travel. These differences remained when controlling for symptom bothersomeness, age, sex, and employment status. In exchange for 1 month of relief from IBS, more than half of the sample reported they would be willing to give up caffeine or alcohol, 40% would give up sex, 24.5% would give up cell phones, and 21.5% would give up the internet for 1 month. CONCLUSIONS: Although the perceived effects of IBS symptoms on productivity are similar among its subtypes, patients with IBS-C and IBS-D report differences in specific areas of daily function.

Chronic nausea and vomiting: evaluation and treatment.

Nausea is an uneasy feeling in the stomach while vomiting refers to the forceful expulsion of gastric contents. Chronic nausea and vomiting represent a diverse array of disorders defined by 4 weeks or more of symptoms. Chronic nausea and vomiting result from a variety of pathophysiological processes, involving gastrointestinal and non-gastrointestinal causes. The prevalence of chronic nausea and vomiting is unclear, although the epidemiology of specific conditions, such as gastroparesis and cyclic vomiting syndrome, is better understood. The economic impact of chronic nausea and vomiting and effects on quality of life are substantial. The initial diagnostic evaluation involves distinguishing gastrointestinal causes of chronic nausea and vomiting (e.g., gastroparesis, cyclic vomiting syndrome) from non-gastrointestinal causes (e.g., medications, vestibular, and neurologic disorders). After excluding anatomic, mechanical and biochemical causes of chronic nausea and vomiting, gastrointestinal causes can be grouped into two broad categories based on the finding of delayed, or normal, gastric emptying. Non-gastrointestinal disorders can also cause chronic nausea and vomiting. As a validated treatment algorithm for chronic nausea and vomiting does not exist, treatment should be based on a thoughtful discussion of benefits, side effects, and costs. The objective of this monograph is to review the evaluation and treatment of patients with chronic nausea and vomiting, emphasizing common gastrointestinal causes.

Consensus Recommendations on Initiating Prescription Therapies for Opioid-Induced Constipation.

OBJECTIVE: Aims of this consensus panel were to determine (1) an optimal symptom-based method for assessing opioid-induced constipation in clinical practice and (2) a threshold of symptom severity to prompt consideration of prescription therapy. METHODS: A multidisciplinary panel of 10 experts with extensive knowledge/experience with opioid-associated adverse events convened to discuss the literature on assessment methods used for opioid-induced constipation and reach consensus on each objective using the nominal group technique. RESULTS: Five validated assessment tools were evaluated: the Patient Assessment of Constipation-Symptoms (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL), Stool Symptom Screener (SSS), Bowel Function Index (BFI), and Bowel Function Diary (BF-Diary). The 3-item BFI and 4-item SSS, both clinician administered, are the shortest tools. In published trials, the BFI and 12-item PAC-SYM are most commonly used. The 11-item BF-Diary is highly relevant in opioid-induced constipation and was developed and validated in accordance with US Food and Drug Administration guidelines. However, the panel believes that the complex scoring for this tool and the SSS, PAC-SYM, and 28-item PAC-QOL may be unfeasible for clinical practice. The BFI is psychometrically validated and responsive to changes in symptom severity; scores range from 0 to 100, with higher scores indicating greater severity and scores >28.8 points indicating constipation. CONCLUSIONS: The BFI is a simple assessment tool with a validated threshold of clinically significant constipation. Prescription treatments for opioid-induced constipation should be considered for patients who have a BFI score of ≥30 points and an inadequate response to first-line interventions.

Trends and racial/ethnic disparities in gluten-sensitive problems in the United States: findings from the National Health and Nutrition Examination Surveys from 1988 to 2012.

OBJECTIVES: Racial disparities in the prevalence of celiac disease (CD) and the number of people without CD avoiding gluten (PWAG) in the United States are unknown. We aimed to describe racial differences in the prevalence of CD and PWAG, and evaluate the trends of CD in the noninstitutionalized civilian adult population of the US between 1988 and 2012. METHODS: A population-based cross-sectional study was conducted using data from the National Health and Nutrition Examination Surveys (NHANES) from 1988 to 1994, 1999 to 2004, and 2009 to 2012. Serum samples from the NHANES participants were tested for CD serology, which included IgA tissue transglutaminase (tTG IgA) and, if findings were abnormal, for IgA endomysial antibodies. Information about adherence to a gluten-free diet was obtained by means of an interviewer-administered questionnaire. RESULTS: In NHANES 2009-2012, the adjusted prevalence of CD was significantly higher (P<0.0001) among non-Hispanic whites (1.0%) than among non-Hispanic blacks (0.2%) and Hispanics (0.3%), whereas the adjusted prevalence of PWAG was significantly higher (P=0.01) in blacks (1.2%) as compared with Hispanics (0.5%) and whites (0.7%). The seroprevalence of CD in adults aged 50 years and older increased from 0.17% (95% confidence interval (CI) 0.03-0.33) in 1988-1994 to 0.44% (95% CI 0.24-0.81) in 2009-2012 (P<0.05). CONCLUSIONS: The overall prevalence of CD increased between 1988 and 2012 and is significantly more common in whites. In addition, a higher proportion of individuals maintaining a gluten-free diet in the absence of a diagnosis of CD are blacks.

Current and future pharmacological treatments for diarrhea-predominant irritable bowel syndrome.

INTRODUCTION: Diarrhea-predominant irritable bowel syndrome (IBS-D) affects about one-third of patients with IBS, which is observed in about 12% of people across five continents. The ultimate goal in this field is to identify the underlying cause of symptoms in order to individualize education of the patient, and to provide optimal treatment of this highly prevalent condition. AREAS COVERED: This review addresses the pharmacological treatments for IBS-D under three categories: drugs for IBS-D (i.e., the 5-HT3 antagonist, alosetron); drugs approved for other indications that are used in IBS-D (e.g., opioid agonists; other 5-HT3 antagonists; serotonergic psychoactive agents; bile acid binders; 5-ASA compounds; probiotics and non-absorbable antibiotics); as well as development of drugs that are likely to impact the management of IBS-D in the future (e.g., drug absorbents; TPH1 inhibitors; mast cell stabilizers; centrally acting benzodiazepines). The final section addresses key findings: regulatory roadblocks; weaknesses in the current research in this field so far and opportunities to address unmet needs including restoration of normal intestinal barrier function or permeability, and suppression within the intestines of local immune activation that is thought to trigger abnormal motor, sensory and secretory functions in IBS-D. EXPERT OPINION: While symptomatic treatment of diarrhea is effective, there is a need for new treatments for the IBS-D complex. Greater understanding of the mechanisms in IBS-D has led to promising approaches to develop more efficacious therapies.

Methods for the assessment of small-bowel and colonic transit.

Transit assessment of the small intestine and colon is relevant in the study of physiology, pathophysiology, and pharmacodynamics, and there is increasing use of small-bowel and colonic transit measurements in clinical practice as well. The main methods that are applied in clinical practice are substrate-hydrogen breath tests for small-bowel transit and radiopaque markers for colonic transit. Over the past 2-3 decades, scintigraphy has become the preferred standard in research studies, particularly for studies of pathophysiology and pharmacodynamics. New approaches include experimental stable isotope measurement of orocecal transit and the recently approved method using a wireless motility capsule that is validated as an accurate measurement of small-bowel and colonic transit.

Epidemiology, mechanisms, and management of diabetic gastroparesis.

Recent evidence of the significant impact of gastroparesis on morbidity and mortality mandates optimized management of this condition. Gastroparesis affects nutritional state, and in diabetics it has deleterious effects on glycemic control and secondary effects on organs that increase mortality. First-line treatments include restoration of nutrition and medications (prokinetic and antiemetic). We review the epidemiology, pathophysiology, impact, natural history, time trends, and treatment of gastroparesis, focusing on diabetic gastroparesis. We discuss pros and cons of current treatment options, including metoclopramide. Second-line therapeutic approaches include surgery, venting gastrostomy or jejunostomy, and gastric electrical stimulation; most of these were developed based on results from open-label trials. New therapeutic strategies for gastroparesis include drugs that target the underlying defects, prokinetic agents such as 5-hydroxytryptamine agonists that do not appear to have cardiac or vascular effects, ghrelin agonists, approaches to pace the stomach, and stem cell therapies.

Perspective: Conflict of interest and professional organizations: considerations and recommendations.

There are differences in conflicts of interest (COIs) in professional organizations compared with academic medical centers. The authors discuss nine major questions pertaining to industry relationships of professional organizations: (1) What makes COI management different in professional membership organizations? (2) What COI challenges are specific to professional organizations? (3) What are potential impacts of perceived or real COIs involving professional organizations and the management of COIs? (4) Is regulation necessary, or should professional organizations proactively resolve COI issues independently? (5) Are guidelines portable from academic medical centers to professional organizations? (6) What approaches may be considered for managing COIs of the organization's leaders? (7) What approaches are reasonable for managing COI issues at professional meetings? (8) What approaches are important for integrity of educational programs, publications, and products? and (9) What approaches are reasonable for managing and enforcing COI guidelines on an ongoing basis? Responses to these questions focus on four principles: First, a code of ethics governing general behavior of members and safeguarding the interest of patients must be in place; second, the monitoring and management of COI for leadership, including, in some cases, recusal from certain activities; third, the pooling and consistent, transparent management of unrestricted grants from corporate sponsors; and, fourth, the management of industry marketing efforts at membership meetings to ensure their appropriateness. The perspectives offered are intended to encourage individuals and learned bodies to further study and provide commentary and recommendations on managing COIs of a professional organization.

The HIPAA authorization form and effects on survey response rates, nonresponse bias, and data quality: a randomized community study.

BACKGROUND: There has been speculation that the Health Insurance Portability and Accountability Act (HIPAA) has muted participation in research but little direct evidence to substantiate those claims exists. OBJECTIVE: To evaluate the effects of including a HIPAA authorization form (HAF) on multiple measures of survey performance. RESEARCH DESIGN, SUBJECTS: A community survey of Olmsted County, Minnesota residents conducted between September 2005 and April 2006. A total of 6939 cases were randomly assigned to 2 experimental conditions where half of the subjects received a 1-page HAF (n = 3469) and the other half did not (n = 3470). MAIN OUTCOME MEASURES: Response rate, nonresponse bias, and data quality. RESULTS: At the end of data collection, a response rate of 39.8% was observed in the HAF condition and 55.0% in the No HAF condition (P < 0.0001). There was a negligible but statistically significant (P < or = 0.001) over-representation of males in the No HAF condition but no difference in the amount of missing data between the 2 groups. However, reports of general health and the percentage of respondents indicating that they were nonsmokers were both significantly (P < or = 0.01) lower in the No HAF condition than in the HAF condition. CONCLUSIONS: Inclusion of a minimally burdensome version of the HAF reduced survey response rates by up to 15 percentage points. This could have implications for a study's statistical power. There was little evidence that the form affected nonresponse bias or data quality.

Managing conflict of interest in clinical practice.

Conflict of interest, even the appearance of potential conflict, has long been a concern for physicians and scientists. Conflict of interest arises when an activity is accompanied by a divergence between personal or institutional benefit when compared to the responsibilities to patients and to society; it arises in the context of research, purchasing, leadership, and investments. Conflict of interest is of concern because it compromises the trust of the patient and of society in the individual physician or the medical center.

Principles and process in the development of the Mayo Clinic's individual and institutional conflict of interest policy.

In 1995, federal regulations required all academic medical centers to implement policies to manage individual financial conflict of interest. At the Mayo Clinic, all staff are salaried, and all medically related intellectual property from the staff belongs to the clinic. Hence, it was necessary to develop a policy for institutional conflict of interest to complement the policy for individual conflicts of interest. This article addresses the principles and process that led to the development of the Mayo Clinic's policies that guide the management of conflict of interest of individuals and of the institution. Empowered by the Bayh-Dole Act, the Mayo Clinic participates in technology transfer through its entity Mayo Medical Ventures. Individual conflicts of interest arising from such technology transfer are associated with Institutional conflicts because all individual intellectual property belongs to the institution, per clinic policy. This policy addresses conflicts of interest that arise in research, leadership, clinical practice, investments, and purchasing. Associated with the statutory annual disclosure on personal consulting and other relationships with Industry, which are guided by federal regulations, all research protocols or grant applications require financial disclosure on initial submission and in annual progress reports. The clinic's Conflict of Interest Review Board was established to review each disclosure and recommend management of individual and institutional conflicts of interest according to policy.