Knowledge of learning disabilities: the relationship with choice, duty of care and non-aversive approaches

The present study examines the relationship between the knowledge of the diagnostic criteria for a learning disability (based on DSM IV criteria), care practices and experience in health care and social care staff. Responses to a questionnaire were analysed in terms of participants emphasis on: recognizing duty of care; enabling choice; non-aversive and aversive strategies. Results indicated that the knowledge of the criteria for a learning disability was limited, with only I6% of the sample correctly identifying all three criteria. There were no significant differences between the two groups in relation to experience or level of knowledge. No clear cut differences were found between the groups in relation to tendency to emphasize a particular management approach, with the strategies adopted appearing to be influenced by vignettes used in this study. Participants tended to give responses that identified both a recognition of their duty of care to clients and the need to enable choice. Limitations of this study are discussed

Progressive Resistance Training and Cancer Testis (PROTRACT) - Efficacy of resistance training on muscle function, morphology and inflammatory profile in testicular cancer patients undergoing chemotherapy: design of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Standard treatment for patients with disseminated germ cell tumors is combination chemotherapy with bleomycin, etoposide and cisplatin (BEP). This treatment is highly effective, but the majority of patients experience severe adverse effects during treatment and are at risk of developing considerable long-term morbidity, including second malignant neoplasms, cardiovascular disease, and pulmonary toxicity. One neglected side effect is the significant muscular fatigue mentioned by many patients with testicular cancer both during and after treatment. Very limited information exists concerning the patho-physiological effects of antineoplastic agents on skeletal muscle. The primary aim of this study is to investigate the effects of BEP-treatment on the skeletal musculature in testicular cancer patients, and to examine whether the expected treatment-induced muscular deterioration can be attenuated or even reversed by high intensity progressive resistance training (HIPRT).</p> <p>Design/Methods</p> <p>The PROTRACT study is a randomized controlled trial in 30 testicular cancer patients undergoing three cycles of BEP chemotherapy. Participants will be randomized to either a 9-week HIPRT program (STR) initiated at the onset of treatment, or to standard care (UNT). 15 healthy matched control subjects (CON) will complete the same HIPRT program. All participants will take part in 3 assessment rounds (baseline, 9 wks, 21 wks) including muscle biopsies, maximum muscle strength tests, whole body DXA scan and blood samples. <it>Primary outcome</it>: mean fiber area and fiber type composition measured by histochemical analyses, satellite cells and levels of protein and mRNA expression of intracellular mediators of protein turnover. Secondary outcomes: maximum muscle strength and muscle power measured by maximum voluntary contraction and leg-extensor-power tests, body composition assessed by DXA scan, and systemic inflammation analyzed by circulating inflammatory markers, lipid and glucose metabolism in blood samples. Health related Quality of Life (QoL) will be assessed by validated questionnaires (EORTC QLQ-C30, SF-36).</p> <p>Discussion</p> <p>This study investigates the muscular effects of antineoplastic agents in testicular cancer patients, and furthermore evaluates whether HIPRT has a positive influence on side effects related to chemotherapy. A more extensive knowledge of the interaction between cytotoxic-induced physiological impairment and exercise-induced improvement is imperative for the future development of optimal rehabilitation programs for cancer patients.</p> <p>Trial Registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN32132990">ISRCTN32132990</a>.</p

High-dose epirubicin is not an alternative to standard-dose doxorubicin in the treatment of advanced soft tissue sarcomas. A study of the EORTC soft tissue and bone sarcoma group.

The activity and toxicity of single-agent standard-dose doxorubicin were compared with that of two schedules of high-dose epirubicin. A total of 334 chemonaive patients with histologically confirmed advanced soft-tissue sarcomas received (A) doxorubicin 75 mg m(-2) on day 1 (112 patients), (B) epirubicin 150 mg m(-2) on day 1 (111 patients) or (C) epirubicin 50 mg m(-2) day(-1) on days 1, 2 and 3 (111 patients); all given as bolus injection at 3-week intervals. A median of four treatment cycles was given. Median age was 52 years (19-70 years) and performance score 1 (0-2). Of 314 evaluable patients, 45 (14%) had an objective tumour response (eight complete response, 35 partial response). There were no differences among the three groups. Median time to progression for groups A, B and C was 16, 14 and 12 weeks, and median survival 45, 47 and 45 weeks respectively. Neither progression-free (P = 0.93) nor overall survival (P = 0.89) differed among the three groups. After the first cycle of therapy, two patients died of infection and one owing to cardiovascular disease, all on epirubicin. Both dose schedules of epirubicin were more myelotoxic than doxorubicin. Cardiotoxicity (> or = grade 3) occurred in 1%, 0% and 2% respectively. Regardless of the schedule, high-dose epirubicin is not a preferred alternative to standard-dose doxorubicin in the treatment of patients with advanced soft-tissue sarcomas

Cancers of unknown primary origin (CUP) are characterized by chromosomal instability (CIN) compared to metastasis of know origin

BACKGROUND: Cancers of unknown primary (CUPs) constitute ~5% of all cancers. The tumors have an aggressive biological and clinical behavior. The aim of the present study has been to uncover whether CUPs exhibit distinct molecular features compared to metastases of known origin. METHODS: Employing genome wide transcriptome analysis, Linear Discriminant Analysis (LDA) and Quadratic Discriminant Analysis (QDA), we defined the putative origins of a large series of CUP and how closely related a particular CUP was to corresponding metastases of known origin. LDA predictions were subsequently used to define a universal CUP core set of differentially expressed genes, that by means of gene set enrichment analysis was exploited to depict molecular pathways characterizing CUP. RESULTS: The analyses show that CUPs are distinct from metastases of known origin. CUPs exhibit inconsistent expression of conventional cancer biomarkers and QDA derived outlier scores show that CUPs are more distantly related to their primary tumor class than corresponding metastases of known origin. Gene set enrichment analysis showed that CUPs display increased expression of genes involved in DNA damage repair and mRNA signatures of chromosome instability (CIN), indicating that CUPs are chromosome unstable compared to metastases of known origin. CONCLUSIONS: CIN may account for the uncommon clinical presentation, chemoresistance and poor outcome in patients with CUP and warrant selective diagnostic strategies and treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1128-x) contains supplementary material, which is available to authorized users

Cognitive dysfunction in early experimental metabolic dysfunction-associated steatotic liver disease is associated with systemic inflammation and neuroinflammation

Background & Aims: Cognitive dysfunction is an increasingly recognised manifestation of metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanistic link remains unclear. The aim of this study was to investigate the hypothesis that experimental MASLD leads to cognitive dysfunction via systemic inflammation and neuroinflammation. Methods: Twenty male Sprague Dawley rats were randomised to a high-fat high-cholesterol (HFHC) diet to induce MASLD, or a standard diet (n = 10/group), for 16 weeks. Assessments included: MASLD severity (histology), neurobehaviour, inflammation (liver, plasma and cerebrospinal fluid), brain microglia and astrocyte activation, and synaptic density. Results: The HFHC diet induced MASLD with extensive steatosis and lobular inflammation without fibrosis. Several plasma cytokines were elevated (CXCL1, IL-6, IL-17, MIP-1α, MCP-1, IL-10; all p <0.05) and correlated with increases in hepatic chemokine gene expression. Cerebrospinal fluid concentrations of CXCL1 were elevated (p = 0.04). In the prefrontal brain cortex, we observed a 19% increase in microglial activation confirmed by Iba1 immunohistochemistry (p = 0.03) and 3H-PK11195 autoradiography (p <0.01). In parallel, synaptic density was reduced to 92%, assessed by 3H-UCB-J autoradiography (p <0.01). MASLD animals exhibited impaired memory to previously encountered objects in the novel object recognition test (p = 0.047) and showed depression-like behaviour evidenced by increased immobility time (p <0.01) and reduced swimming time (p = 0.03) in the forced swim test. Conclusions: Experimental non-fibrotic MASLD, as a model to reflect the early stage of human disease, results in cognitive impairment and depression-like behaviour. This is associated with an inflammatory phenotype not only in the liver but also in the plasma and brain, which together with diminished synaptic density, provides a pathophysiological link between liver disease and cognitive dysfunction in MASLD. Impact and implications: Cognitive dysfunction is an increasingly recognised comorbidity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), yet the underlying mechanisms remain unclear. This study provides evidence of impaired memory and depression-like symptoms in early experimental MASLD and indicates that hepatic inflammation may drive a systemic inflammatory response, resulting in neuroinflammation and reduced brain synaptic density. The evidence of impaired memory in MASLD and establishing its underlying pathophysiological link provides insights that could guide the development of potential new treatments for this increasingly common condition in people of working age. The study also emphasises the need to develop better tools for clinical cognitive testing, which will enable physicians to assess and manage brain dysfunction early in MASLD

Development and Validation of a Risk Score for Febrile Neutropenia After Chemotherapy in Patients With Cancer: The FENCE Score

Background: Febrile neutropenia (FN) after chemotherapy causes a high burden of morbidity and mortality. We aimed to develop and validate a risk score to predict FN in the first cycle of chemotherapy. Methods: We included patients with solid cancers and diffuse large B-cell lymphomas at Rigshospitalet, University of Copenhagen, 2010-2016. Predictors of FN were analyzed using Poisson regression and random split-sampling. Results: Among 6294 patients in the derivation cohort, 360 developed FN. Female sex, older age, cancer type, disease stage, low albumin, elevated bilirubin, low creatinine clearance, infection before chemotherapy, and number of and type of chemotherapy drugs predicted FN. Compared with those at low risk (n = 2520, 40.0%), the incidence rate ratio of developing FN was 4.8 (95% confidence interval [CI] = 2.9 to 8.1), 8.7 (95% CI = 5.3 to 14.1) and 24.0 (95% CI = 15.2 to 38.0) in the intermediate (n = 1294, 20.6%), high (n = 1249, 19.8%) and very high (n = 1231, 19.6%) risk groups, respectively, corresponding to a number needed to treat with granulocyte colony-stimulating factors to avoid one FN event in the first cycle of 284, 60, 34 and 14. The discriminatory ability (Harrell's C-statistic = 0.80, 95% CI = 0.78 to 0.82) was similar in the validation cohort (n = 3163) (0.79, 95% CI = 0.75 to 0.82). Conclusion: We developed and internally validated a risk score for FN in the first cycle of chemotherapy. The FENCE score is available online and provides good differentiation of risk groups