Phorbol myristate acetateex vivo model of enhanced colonic epithelial permeability

The initiating mechanisms involved in colonic injury are currently unknown. The goal of the current study was to examine the role of the inflammatory mediators reactive oxygen metabolites and proteases in anex vivo model of selective epithelial permeability. Rats were prepared with exteriorized colonic chambers to which the protein kinase C (PKC) activator phorbol myristate acetate (PMA) was added in doses ranging from 5 to 800 g. PMA caused a dose-dependent transient increase in epithelial permeability, but had no significant effect on microvascular permeability. There was no accumulation of neutrophils and no apparent histological changes. PMA acts via a PKC-dependent mechanism, as assessed using the PKC-inactive phorbol analog 4-phorbol didecanoate, and the response is tachyphylactic. The mechanism is independent of reactive oxygen metabolites and proteases, as shown by the lack of effect of the free radical scavengers superoxide dismutase and catalase and the general serine protease inhibitor soybean trypsin inhibitor. The classic inflammatory process does not appear to be involved in the PMA-induced epithelial permeability changes. This finding suggests that noninflammatory mechanisms may regulate the increased epithelial permeability induced by PMA. Further study to elucidate these mechanisms is of importance for understanding both normal gastrointestinal physiology and initiation of pathology.     

Gender differences in the clinical competence of residents in internal medicine

OBJECTIVE: To study the differences between cognitive and noncognitive skills of men and those of women entering internal medicine. DESIGN: Comparison of program directors' ratings of overall clinical competence and its specific components and pass rates for men and women taking the Certifying Examinations in Internal Medicine in 1984-1987. PARTICIPANTS: 14,340 U.S. and Canadian graduates taking the Certifying Examinations of the American Board of Internal Medicine for the first time in 1984-1987. MEASUREMENTS/RESULTS: Average program directors' ratings of overall competence were 6.70-6.78 for men and 6.60-6.71 for women. The greatest differences in ratings of specific components of competence were in the areas of medical knowledge and procedural skills, where men were rated higher than women, and humanistic qualities, where women were rated higher than men. Pass rates were stable over the four years of the study, and ranged from 85 to 86% for men and from 79 to 81% for women. Men consistently performed slightly better than women regardless of the type of residency or quality of medical school attended. CONCLUSIONS: Small but consistent differences were found in the performances of men and those of women completing training in Internal Medicine as measured by program directors' ratings and ABIM Certifying Examination performances.     

What is a new drug worth? An innovative model for performance‐based pricing

This article focuses on a novel method to derive prices for new pharmaceuticals by making price a function of drug performance. We briefly review current models for determining price for a new product and discuss alternatives that have historically been favoured by various funding bodies. The progressive approach to drug pricing, proposed herein, may better address the views and concerns of multiple stakeholders in a developed healthcare system by acknowledging and incorporating input from disparate parties via comprehensive and successive negotiation stages. In proposing a valid construct for performance‐based pricing, the following model seeks to achieve several crucial objectives: earlier and wider access to new treatments; improved transparency in drug pricing; multi‐stakeholder involvement through phased pricing negotiations; recognition of innovative product performance and latent changes in value; an earlier and more predictable return for developers without sacrificing total return on investment (ROI); more involved and informed risk sharing by the end‐user.     

Patients' satisfaction with fast‐track surgery in gynaecological oncology

This study investigates the experience and satisfaction with care of fast‐tracked gynaecological patients. The Sydney Gynaecological Oncology Group, New South Wales, Australia, has previously shown the benefits of a fast‐track surgery programme for gynaecology patients with both complex benign gynaecological pathology and gynaecological malignancy. The question of whether these benefits translate into a positive experience for fast‐tracked patients, in the context of their hospital stay and healthcare team care, has not been previously explored in detail. A self‐administered satisfaction questionnaire incorporating the European Organisation for Research and Treatment of Cancer (EORTC) cancer in‐patient satisfaction with care measure (INPATSAT‐32) questionnaire with additional questions was administered to 106 gynaecology participants at Royal Prince Alfred Hospital. Participants reported high levels of satisfaction with patient care and support received from doctors, ward nurses and the hospital as a service and care organisation, within the context of a fast‐track surgical programme. Early hospital discharge after gynaecological surgery results in both enhanced recovery after surgery (ERAS) and high levels of patient satisfaction.     

The effect of dietary intake changes on nutritional status in acute leukaemia patients after first induction chemotherapy

This study aimed to evaluate how changes in dietary intake among acute lymphoblastic and acute myeloid leukaemia (ALL and AML) patients affect nutritional status after the first induction chemotherapy. Dietary intake was assessed using 24‐h recall and a 136‐item food frequency questionnaire. Nutritional status was assessed by Patients Subjective Global Assessment questionnaire before starting induction therapy and again after 1 month. All newly diagnosed acute leukaemia patients aged 15 years old and older who attended three referral hospitals for initiation of their induction chemotherapy were included in the sample selection provided that they gave informed consent. A total of 30 AML and 33 ALL patients participated in the study. Dietary intake and nutritional status worsened after the chemotherapy treatment. Dietary intake in terms of macronutrients, micronutrients, food variety and diet diversity score changed significantly after the induction chemotherapy. No significant relationship was found between the changes in dietary indices and nutritional status. Chemotherapy‐related side effects as an additional factor to cancer itself could affect dietary intake of leukaemia patients. The effectiveness of an early assessment of nutritional status and dietary intake should be further investigated in order to deter further deterioration.     

Inequalities in reported cancer patient experience by socio‐demographic characteristic and cancer site: evidence from respondents to the English Cancer Patient Experience Survey

Patient experience is a critical dimension of cancer care quality. Understanding variation in experience among patients with different cancers and characteristics is an important first step for designing targeted improvement interventions. We analysed data from the 2011/2012 English Cancer Patient Experience Survey (n = 69 086) using logistic regression to explore inequalities in care experience across 64 survey questions. We additionally calculated a summary measure of variation in patient experience by cancer, and explored inequalities between patients with cancers treated by the same specialist teams. We found that younger and very old, ethnic minority patients and women consistently reported worse experiences across questions. Patients with small intestine/rarer lower gastrointestinal, multiple myeloma and hepatobiliary cancers were most likely to report negative experiences whereas patients with breast, melanoma and testicular cancer were least likely (top‐to‐bottom odds ratio = 1.91, P < 0.0001). There were also inequalities in experience among patients with cancers treated by the same specialty for five of nine services (P < 0.0001). Specifically, patients with ovarian, multiple myeloma, anal, hepatobiliary and renal cancer reported notably worse experiences than patients with other gynaecological, haematological, gastrointestinal and urological malignancies respectively. Initiatives to improve cancer patient experience across oncology services may be suitably targeted on patients at higher risk of poorer experience.