Effectiveness of a stigma awareness intervention on reemployment of people with mental health issues/mental illness:A cluster randomised controlled trial

PurposeA barrier for reemployment of people with mental health issues/mental illness (MHI) is workplace stigma and discrimination. In this RCT the effectiveness of a stigma-awareness intervention addressing finding work, retaining work and decisional stress were evaluated.MethodsA cluster RCT was conducted in 8 Dutch municipal practices. Randomisation took place at practice level. Participants were unemployed people with MHI, receiving social benefits. The intervention consisted of a decision aid for workplace disclosure for participants and a 2 × 3 h stigma-awareness training for their employment specialists. Primary outcomes were measured at baseline, 3-, 6- and 12-months. Multilevel analyses, containing random intercepts of participants nested in organizations, were conducted to analyse the effects of the intervention.ResultsParticipants (N = 153) were randomized to an experimental (n = 76) or control group (n = 77). At six months, significantly more participants of the experimental group (51%) had found work compared to the control group (26%). At twelve months, significantly more participants of the experimental group (49%) had retained work compared to the control group (23%). Intention-to-treat analyses showed that randomization to the experimental group was associated with finding (OR(95%CI) = 7.78(1.33–45.53), p = 0.02) and retaining (OR(95%CI) = 12.15(2.81–52.63), p < 0.01) work more often at twelve months. Analyses showed that the experimental and control group did not differ in decisional stress.ConclusionsOur stigma awareness intervention was effective for finding and retaining work. As the percentage of people who found and retained work almost doubled, this suggests that on a societal level, a vast number of unemployed people could be reemployed with a relatively simple intervention.Trial RegistrationThe study was retrospectively registered at the Dutch Trial Register (TRN: NL7798, date: 04-06-2019)

Outcomes of First-Line Chemotherapy in Patients with Advanced or Metastatic Leiomyosarcoma of Uterine and Non-Uterine Origin

Although leiomyosarcomas (LMSs) form the largest subgroup of soft tissue sarcomas (STSs), the efficacy of chemotherapy in this group is largely unclear, partly because older studies are contaminated with gastrointestinal stromal tumors (GISTs). In this retrospective study we investigated the outcome of first line chemotherapy in 65 patients with unresectable or metastatic LMS. The overall response rate (ORR) was 18%; and the median progression-free (PFS) and overall survival (OS) were 3.8 and 9.7 months respectively. No statistically significant differences in outcomes for uterine and non-uterine LMS were found. In non-uterine LMS, however, the PFS and OS seemed to be longer for females than for males, potentially negatively affecting outcomes in this group. If our observations are confirmed in other series, they would suggest that studies performed in STS patients should not only stratify for histological subtype but also for uterine versus non-uterine LMS and for gender

ras Oncogene Activation Does Not Induce Sensitivity to Natural Killer Cell—Mediated Lysis in Human Melanoma

An important phenomenon in tumor immunology that has come under recent attention is the impact of oncogene activation in tumor cells on the sensitivity to lysis by immune effector cells. Several studies suggested that transfer of an activated ras oncogene into cultured rodent fibroblasts induces susceptibility to natural killer cell (NK)-mediated lysis. Experiments using human tumor cells, however, have produced conflicting data on the effect of ras activation in this respect. In studying the activation of the oncogene c-myc, which is often overexpressed in human melanoma, we have found that in cell lines expressing high levels of Myc protein, the sensitivity to lysis by NK cells was dramatically increased due to reduced expression of Human Leukocyte Antigen B locus products. Since the N-ras oncogene was found to be activated in 15% of human melanomas, we examined the possibility that in melanoma, in analogy to the murine systems, the mutated ras oncogene may influence NK susceptibility of human melanoma cells. Two N-ras genes harboring frequently found mutations were cloned into an expression vector. Transfection of the IGR39D melanoma cell line with wildtype and mutant N-ras constructs yielded several ras-expressing clones that were tested for NK sensitivity. Neither high expression of the wildtype N-ras protein, nor expression of two mutant proteins (N61-arg, N61-lys) was shown to result in enhanced NK-mediated lysis. We conclude that activation of ras oncogenes does not lead to the induction of an NK-sensitive phenotype in human melanoma cells. J Invest Dermatol 103:117S–121S, 199

Surgery for Ampullary Cancer in a Patient with Pancreatic Lipomatosis Caused by Cystic Fibrosis

A patient with cystic fibrosis (CF) with pancreatic insufficiency presented with jaundice due to an ampullary tumour. CF is known for a higher incidence of gastrointestinal malignancies. The patient suffered from pancreatic insufficiency. At computed tomography (CT), pancreatic lipomatosis with absence of the pancreatic duct was seen. This is uncommon, also in patients with CF. During surgery, a total pancreatectomy was performed, because there was no possibility to construct a duct to mucosa anastomosis due to the absence of the pancreatic duct and more importantly the pancreas was already afunctional. The presence of lipomatosis increases the risk of leakage at the pancreaticojejunal anastomosis. Therefore, it is important to take this phenomenon, in this case already visible on the preoperative CT scan, into account during the workup for surgery

Differences in neuropsychiatric symptoms between nursing home residents with young-onset dementia and late-onset dementia

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Histological response to radiotherapy is an early event in myxoid liposarcoma

Myxoid liposarcoma; Personalized medicine; RadiotherapyLiposarcoma mixoide; Medicina personalizada; RadioterapiaLiposarcoma mixoide; Medicina personalitzada; RadioteràpiaCompared to other sarcomas, myxoid liposarcoma (MLS) is exceptionally sensitive to radiation therapy, but the underlying mechanism remains unknown. The objective was to assess the tissue-based changes in MLS during and after neoadjuvant radiotherapy in 26 patients of the DOREMY trial. Morphological assessment was performed on biopsies pre-treatment, after 8 fractions, 16 factions, and after surgical resection and included percentage of viable tumor cells, hyalinization, necrosis, and fatty maturation. Furthermore, immunohistochemistry was performed for apoptosis (cleaved caspase-3), anti-apoptosis (Bcl-2), activity of mTOR signaling (phospho-S6), hypoxia (CAIX), proliferation (Ki67), inflammation (CD45 and CD68), and microvessel density (CD34 Chalkley count). A pronounced reduction in vital tumor cells was observed early with a drop to 32.5% (median) tumor cells (IQR 10–93.8%) after 8 fractions. This decreased further to 10% (IQR 5–30%) after 16 fractions and 7.5% (IQR 5–15%) in the surgical specimen. All but one patient had an excellent response with < 50% remaining tumor cells. Inversely, treatment response was mainly observed as hyalinization and less often as fatty maturation. Additionally, a decrease of inflammatory cells was noticed especially during the first eight fractions. Microvessel density remained stable over time. Immunohistochemical markers for apoptosis, anti-apoptosis, activity of mTOR signaling, proliferation, and hypoxia did not show any marked changes within the remaining tumor cells during and after radiotherapy. As a modest dose of neoadjuvant radiotherapy induces profound tissue changes in MLS, mainly during the first 8 fractions, current findings might suggest that in a carefully selected patient population further deintensification of radiotherapy might be explored

Antithrombotic Management in Adult Kidney Transplantation: A European survey study

In kidney transplantation (KTx), renal graft thrombosis (RGT) is one of the main reasons for early graft loss. Although evidence-based guidance on prevention of RGT is lacking, thromboprophylaxis is widely used. The aim of this survey was to obtain a European view of the different thromboprophylactic strategies applied in KTx. An online 22-question survey, addressed to KTx professionals, was distributed by email and via platforms of the European Society for Organ Transplantation. Seventy-five responses (21 countries, 51 centers) were received: 75% had over 10 years' clinical experience, 64% were surgeons, 29% nephrologists, and 4% urologists. A written antithrombotic management protocol was available in 75% of centers. In 8 (16%) centers, respondents contradicted each other regarding the availability of a written protocol. Thromboprophylaxis is preferred by 78% of respondents, independent of existing antithrombotic management protocols. Ninety-two percent of respondents indicated that an anticipated bleeding risk is the main reason to discontinue chronic antithrombotic therapy preoperatively. Intraoperatively, 32% of respondents administer unfractionated heparin (400-10,000 international units with a median of 5,000) in selected cases. Despite an overall preference for perioperative thromboprophylaxis in KTx, there is a high variation within Europe regarding type, timing, and dosage, most likely due to the paucity of high-quality studies. Further research is warranted in order to develop better guidelines.</p

The cardiac sodium channel displays differential distribution in the conduction system and transmural heterogeneity in the murine ventricular myocardium

Cardiac sodium channels are responsible for conduction in the normal and diseased heart. We aimed to investigate regional and transmural distribution of sodium channel expression and function in the myocardium. Sodium channel Scn5a mRNA and Na(v)1.5 protein distribution was investigated in adult and embryonic mouse heart through immunohistochemistry and in situ hybridization. Functional sodium channel availability in subepicardial and subendocardial myocytes was assessed using patch-clamp technique. Adult and embryonic (ED14.5) mouse heart sections showed low expression of Na(v)1.5 in the HCN4-positive sinoatrial and atrioventricular nodes. In contrast, high expression levels of Na(v)1.5 were observed in the HCN4-positive and Cx43-negative AV or His bundle, bundle branches and Purkinje fibers. In both ventricles, a transmural gradient was observed, with a low Na(v)1.5 labeling intensity in the subepicardium as compared to the subendocardium. Similar Scn5a mRNA expression patterns were observed on in situ hybridization of embryonic and adult tissue. Maximal action potential upstroke velocity was significantly lower in subepicardial myocytes (mean +/- SEM 309 +/- 32 V/s; n = 14) compared to subendocardial myocytes (394 +/- 32 V/s; n = 11; P < 0.05), indicating decreased sodium channel availability in subepicardium compared to subendocardium. Scn5a and Na(v)1.5 show heterogeneous distribution patterns within the cardiac conduction system and across the ventricular wall. This differential distribution of the cardiac sodium channel may have profound consequences for conduction disease phenotypes and arrhythmogenesis in the setting of sodium channel diseas

The impact of a supportive supervision intervention on health workers in Niassa, Mozambique: a cluster-controlled trial

BACKGROUND: Regular supportive supervision is critical to retaining and motivating staff in resource-constrained settings. Previous studies have shown the particular contribution that supportive supervision can make to improving job satisfaction amongst over-stretched health workers in such settings. METHODS: The Support, Train and Empower Managers (STEM) study designed and implemented a supportive supervision intervention and measured its' impact on health workers using a controlled trial design with a three-arm pre- and post-study in Niassa Province in Mozambique. Post-intervention interviews with a small sample of health workers were also conducted. RESULTS: The quantitative measurements of job satisfaction, emotional exhaustion and work engagement showed no statistically significant differences between end-line and baseline. The qualitative data collected from health workers post the intervention showed many positive impacts on health workers not captured by this quantitative survey. CONCLUSIONS: Health workers perceived an improvement in their performance and attributed this to the supportive supervision they had received from their supervisors following the intervention. Reports of increased motivation were also common. An unexpected, yet important consequence of the intervention, which participants directly attributed to the supervision intervention, was the increase in participation and voice amongst health workers in intervention facilities