Anti-TNF-α treatment for deep endometriosis-associated pain: a randomized placebo-controlled trial

BACKGROUND: Endometriosis is associated with an inflammatory response. Hence infliximab, an anti-TNF-alpha monoclonal antibody, might relieve pain. METHODS: A randomized placebo-controlled trial was designed with 21 women with severe pain and a rectovaginal nodule of at least 1 cm. After 1 month of observation, three infusions of infliximab (5 mg/kg) or placebo were given. Surgery was performed 3 months later and follow-up continued for 6 months. The primary end-point was pain (dysmenorrhea, deep dyspareunia and non-menstrual pain) rated at each visit by the clinician and on a daily basis by the patient who in addition scored pain by visual analog pain scale and analgesia intake. Secondary end-points included the volume of the endometriotic nodule, pelvic tenderness and the visual appearance of endometriotic lesions at laparoscopy. RESULTS: Pain severity decreased during the treatment by 30% in both the placebo (P < 0.001) and infliximab groups (P < 0.001). However, no effect of infliximab was observed for any of the outcome measures. After surgery, pain scores decreased in both groups to less than 20% of the initial value. CONCLUSIONS: Infliximab appears not to affect pain associated with deep endometriosis. Treatment is associated with an important placebo effect. After surgery, pain decreases to less than 20%. Trials registration number ClinicalTrials.gov: NCT00604864

Assessing the health impact of transnational corporations: its importance and a framework

BACKGROUND: The adverse health and equity impacts of transnational corporations' (TNCs) practices have become central public health concerns as TNCs increasingly dominate global trade and investment and shape national economies. Despite this, methodologies have been lacking with which to study the health equity impacts of individual corporations and thus to inform actions to mitigate or reverse negative and increase positive impacts. METHODS: This paper reports on a framework designed to conduct corporate health impact assessment (CHIA), developed at a meeting held at the Rockefeller Foundation Bellagio Center in May 2015. RESULTS: On the basis of the deliberations at the meeting it was recommended that the CHIA should be based on ex post assessment and follow the standard HIA steps of screening, scoping, identification, assessment, decision-making and recommendations. A framework to conduct the CHIA was developed and designed to be applied to a TNC's practices internationally, and within countries to enable comparison of practices and health impacts in different settings. The meeting participants proposed that impacts should be assessed according to the TNC's global and national operating context; its organisational structure, political and business practices (including the type, distribution and marketing of its products); and workforce and working conditions, social factors, the environment, consumption patterns, and economic conditions within countries. CONCLUSION: We anticipate that the results of the CHIA will be used by civil society for capacity building and advocacy purposes, by governments to inform regulatory decision-making, and by TNCs to lessen their negative health impacts on health and fulfil commitments made to corporate social responsibility.IS

Sprouted Innervation into Uterine Transplants Contributes to the Development of Hyperalgesia in a Rat Model of Endometriosis

Endometriosis is an enigmatic painful disorder whose pain symptoms remain difficult to alleviate in large part because the disorder is defined by extrauteral endometrial growths whose contribution to pain is poorly understood. A rat model (ENDO) involves autotransplanting on abdominal arteries uterine segments that grow into vascularized cysts that become innervated with sensory and sympathetic fibers. ENDO rats exhibit vaginal hyperalgesia. We used behavioral, physiological, and immunohistochemical methods to test the hypothesis that cyst innervation contributes to the development of this hyperalgesia after transplant. Rudimentary sensory and sympathetic innervation appeared in the cysts at two weeks, sprouted further and more densely into the cyst wall by four weeks, and matured by six weeks post-transplant. Sensory fibers became abnormally functionally active between two and three weeks post-transplant, remaining active thereafter. Vaginal hyperalgesia became significant between four and five weeks post-transplant, and stabilized after six to eight weeks. Removing cysts before they acquired functional innervation prevented vaginal hyperalgesia from developing, whereas sham cyst removal did not. Thus, abnormally-active innervation of ectopic growths occurs before hyperalgesia develops, supporting the hypothesis. These findings suggest that painful endometriosis can be classified as a mixed inflammatory/neuropathic pain condition, which opens new avenues for pain relief. The findings also have implications beyond endometriosis by suggesting that functionality of any transplanted tissue can be influenced by the innervation it acquires

Metachronic malignant transformation of small bowel and rectal endometriosis in the same patient

BACKGROUND: Malignant transformation of intestinal endometriosis is a rare event with an unknown rate of incidence. Metachronous progression of endometriosis to adenocarcinoma from two distant intestinal foci happening in the same patient has not been previously reported. CASE PRESENTATION: We describe a case of metachronic transformation of ileal and rectal endometriosis into an adenocarcinoma occurring in a 45-year-old female without macroscopic pelvic involvement of her endometriosis. First, a right colectomy was performed due to intestinal obstruction by an ileal mass. Pathological examination revealed an ileal endometrioid adenocarcinoma and contiguous microscopic endometriotic foci. Twenty months later, a rectal mass was discovered. An endoscopic biopsy revealed an adenocarcinoma. En bloc anterior rectum resection, hysterectomy and bilateral salpingectomy were performed. A second endometrioid adenocarcinoma arising from a focus of endometriosis within the wall of the rectum was diagnosed. CONCLUSION: Intestinal endometriosis should be considered a premalignant condition in premenopausal women

The interplay between structure and agency in shaping the mental health consequences of job loss

Main themes that emerged from the qualitative exploration of the psychological distress of job loss included stress, changes to perceived control, loss of self-esteem, shame and loss of status, experiencing a grieving process, and financial strain. Drawing on two models of agency we identified the different ways workers employed their agency, and how their agency was enabled, but mainly constrained, when dealing with job loss consequences. Respondents’ accounts support the literature on the moderating effects of economic resources such as redundancy packages. The results suggest the need for policies to put more focus on social, emotional and financial investment to mediate the structural constraints of job loss. Our study also suggests that human agency must be understood within an individual’s whole of life circumstances, including structural and material constraints, and the personal or interior factors that shape these circumstances.The authors acknowledge support from the National Health and Medical Research Council Capacity Building Grant (324724). The research was supported by the SA Department of Health and the SA Department of Families and Communities through the Human Services Research and Innovation Program (HSRIP), and the Australian Research Council Linkage Program (LP0562288), with the Department of Health (DOH) serving as Industry Partner. Professor Fran Baum was supported by an ARC Federation Fellowship and Drs Newman and Ziersch by the SA Premier’s Science and Research Fund

Knowledge-to-action processes in SHRTN collaborative communities of practice: A study protocol

<p>Abstract</p> <p>Background</p> <p>The Seniors Health Research Transfer Network (SHRTN) Collaborative is a network of networks that work together to improve the health and health care of Ontario seniors. The collaborative facilitates knowledge exchange through a library service, knowledge brokers (KBs), local implementation teams, collaborative technology, and, most importantly, Communities of Practice (CoPs) whose members work together to identify innovations, translate evidence, and help implement changes.</p> <p>This project aims to increase our understanding of knowledge-to-action (KTA) processes mobilized through SHRTN CoPs that are working to improve the health of Ontario seniors. For this research, KTA refers to the movement of research and experience-based knowledge between social contexts, and the use of that knowledge to improve practice. We will examine the KTA processes themselves, as well as the role of human agents within those processes. The conceptual framework we have adopted to inform our research is the Promoting Action on Research Implementation in Health Services (PARIHS) framework.</p> <p>Methods/design</p> <p>This study will use a multiple case study design (minimum of nine cases over three years) to investigate how SHRTN CoPs work and pursue knowledge exchange in different situations. Each case will yield a unique narrative, framed around the three PARIHS dimensions: evidence, context, and facilitation. Together, the cases will shed light on how SHRTN CoPs approach their knowledge exchange initiatives, and how they respond to challenges and achieve their objectives. Data will be collected using interviews, document analysis, and ethnographic observation.</p> <p>Discussion</p> <p>This research will generate new knowledge about the defining characteristics of CoPs operating in the health system, on leadership roles in CoPs, and on the nature of interaction processes, relationships, and knowledge exchange mechanisms. Our work will yield a better understanding of the factors that contribute to the success or failure of KTA initiatives, and create a better understanding of how local caregiving contexts interact with specific initiatives. Our participatory design will allow stakeholders to influence the practical usefulness of our findings and contribute to improved health services delivery for seniors.</p

Neuroendocrine–immune disequilibrium and endometriosis: an interdisciplinary approach

Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, protein–glycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis