How People with Multiple Sclerosis Rate Their Quality of Life: An EQ-5D Survey via the UK MS Register

The EQ-5D is a widely-used, standardised, quality of life measure producing health profiles, indices and states. The aims of this study were to assess the role of various factors in how people with Multiple Sclerosis rate their quality of life, based on responses to the EQ-5D received via the web portal of the UK MS Register.The 4516 responses to the EQ-5D (between May 2011 and April 2012) were collated with basic demographic and descriptive MS data and the resulting dataset was analysed in SPSS (v.20).The mean health state for people with MS was 59.73 (SD 22.4, median 61), compared to the UK population mean of 82.48 (which is approximately 1SD above the cohort mean). The characteristics of respondents with high health states (at or above +1SD) were: better health profiles (most predictive dimension: Usual Activities), higher health indices, younger age, shorter durations of MS, female gender, relapsing-remitting MS, higher educational attainment and being in paid employment (all p-values<0.001). Conversely, the characteristics of respondents with low health states (at or below -1SD) were: poorer health profiles (most predictive dimension: Mobility), lower health indices, older age, longer durations of MS, male gender, progressive MS, lower educational attainment and having an employment status of sick/disabled (p = 0.0014 for age, all other p-values<0.001). Particular living arrangements were not associated with either the high or low health status groups.This large-scale study has enabled in-depth analyses on how people with MS rate their quality of life, and it provides new knowledge on the various factors that contribute to their self-assessed health status. These findings demonstrate the impact of MS on quality of life, and they can be used to inform care provision and further research, to work towards enhancing the quality of life of people with MS

Prolactin Receptor in Primary Hyperparathyroidism – Expression, Functionality and Clinical Correlations

<div><h3>Background</h3><p>Primary hyperparathyroidism (PHPT) is an endocrine disorder most commonly affecting women, suggesting a role for female hormones and/or their receptors in parathyroid adenomas. We here investigated the prolactin receptor (PRLr) which is associated with tumours of the breast and other organs.</p> <h3>Methodology/Principal Findings</h3><p>PRLr expression was investigated in a panel of 37 patients with sporadic parathyroid tumours and its functionality in cultured parathyroid tumour cells. In comparison with other tissues and breast cancer cells, high levels of prolactin receptor gene (<em>PRLR</em>) transcripts were demonstrated in parathyroid tissues. PRLr products of 60/70 kDa were highly expressed in all parathyroid tumours. In addition varying levels of the 80 kDa PRLr isoform, with known proliferative activity, were demonstrated. In parathyroid tumours, PRLr immunoreactivity was observed in the cytoplasm (in all cases, n = 36), cytoplasmic granulae (n = 16), the plasma membrane (n = 12) or enlarged lysosomes (n = 4). In normal parathyroid rim (n = 28), PRLr was uniformly expressed in the cytoplasm and granulae. In <em>in vitro</em> studies of short-term cultured human parathyroid tumour cells, prolactin stimulation was associated with significant transcriptional changes in JAK/STAT, RIG-I like receptor and type II interferon signalling pathways as documented by gene expression profiling. Moreover, <em>PRLR</em> gene expression in parathyroid tumours was inversely correlated with the patients’ plasma calcium levels.</p> <h3>Conclusions</h3><p>We demonstrate that the prolactin receptor is highly abundant in human parathyroid tissues and that PRLr isoforms expression and PRLr subcellular localisation are altered in parathyroid tumours. Responsiveness of PRLr to physiological levels of prolactin was observed in the form of increased PTH secretion and altered gene transcription with significant increase of RIG-I like receptor, JAK-STAT and Type II interferon signalling pathways. These data suggest a role of the prolactin receptor in parathyroid adenomas.</p> </div

Monocytes induce STAT3 activation in human mesenchymal stem cells to promote osteoblast formation

A major therapeutic challenge is how to replace bone once it is lost. Bone loss is a characteristic of chronic inflammatory and degenerative diseases such as rheumatoid arthritis and osteoporosis. Cells and cytokines of the immune system are known to regulate bone turnover by controlling the differentiation and activity of osteoclasts, the bone resorbing cells. However, less is known about the regulation of osteoblasts (OB), the bone forming cells. This study aimed to investigate whether immune cells also regulate OB differentiation. Using in vitro cell cultures of human bone marrow-derived mesenchymal stem cells (MSC), it was shown that monocytes/macrophages potently induced MSC differentiation into OBs. This was evident by increased alkaline phosphatase (ALP) after 7 days and the formation of mineralised bone nodules at 21 days. This monocyte-induced osteogenic effect was mediated by cell contact with MSCs leading to the production of soluble factor(s) by the monocytes. As a consequence of these interactions we observed a rapid activation of STAT3 in the MSCs. Gene profiling of STAT3 constitutively active (STAT3C) infected MSCs using Illumina whole human genome arrays showed that Runx2 and ALP were up-regulated whilst DKK1 was down-regulated in response to STAT3 signalling. STAT3C also led to the up-regulation of the oncostatin M (OSM) and LIF receptors. In the co-cultures, OSM that was produced by monocytes activated STAT3 in MSCs, and neutralising antibodies to OSM reduced ALP by 50%. These data indicate that OSM, in conjunction with other mediators, can drive MSC differentiation into OB. This study establishes a role for monocyte/macrophages as critical regulators of osteogenic differentiation via OSM production and the induction of STAT3 signalling in MSCs. Inducing the local activation of STAT3 in bone cells may be a valuable tool to increase bone formation in osteoporosis and arthritis, and in localised bone remodelling during fracture repair

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700