Cross-sectional analysis of baseline differences of candidates for rotator cuff surgery: a sex and gender perspective

<p>Abstract</p> <p>Background</p> <p>The word "sex" refers to biological differences between men and women. Gender refers to roles, behaviors, activities, and attributes that a given society considers appropriate for men and women. Traditionally, treatment decisions have been based on patient's sex without including the gender. Assessment of disability secondary to musculoskeletal problems would not be complete or accurate unless potentially relevant biological and non-biological aspects of being a man or woman are taken into consideration. The purposes of this study were to: 1) investigate the difference in pre-operative characteristics between men and women who were candidates for rotator cuff surgery; and, 2) assess the relationship between level of disability and factors that represent sex and factors that signify gender.</p> <p>Method</p> <p>This was a cross-sectional study. The primary outcome measure of disability was a disease-specific outcome measure, the Western Ontario Rotator Cuff (WORC) index, and independent variables were sex, age, hand dominance, shoulder side involvement, BMI, co-morbidity, medication use, work status, smoking habits, strength, range of motion, level of pathology, concurrent osteoarthritis, expectations for recovery, and participation restriction. Parametric, non-parametric, univariable, subgroup, and multivariable analyses were conducted.</p> <p>Results</p> <p>One hundred and seventy patients were included in the study. The mean age was 57 ± 11, 85 were females. Women reported higher levels of disability despite similar or lower levels of pathology. Scores of the WORC were strongly influenced by factors that represented "gender" such as participation restriction (F = 28.91, p < 0.0001) and expectations for improved activities of daily living (F = 5.80, p = 0.004). Painfree combined range of motion, which represented an interaction between "sex" and "gender" was also associated with disability after being adjusted for all other relevant baseline factors (F = 25.82, p < 0.0001).</p> <p>Conclusion</p> <p>Gender-related factors such as expectations and participation limitations have an independent impact on disability in men and women undergoing rotator cuff related surgery.</p

A Phase II Trial of Sorafenib in Metastatic Melanoma with Tissue Correlates

Sorafenib monotherapy in patients with metastatic melanoma was explored in this multi-institutional phase II study. In correlative studies the impact of sorafenib on cyclin D1 and Ki67 was assessed. mutational status and clinical activity. No significant changes in expression of cyclin D1 or Ki67 with sorafenib treatment were demonstrable in the 15 patients with pre-and post-treatment tumor samples. mutational status of the tumor was not associated with clinical activity and no significant effect of sorafenib on cyclin D1 or Ki67 was seen, suggesting that sorafenib is not an effective BRAF inhibitor or that additional signaling pathways are equally important in the patients who benefit from sorafenib

Relationship between physician-adjudicated adverse events and patient-reported health-related quality of life in a phase II clinical trial (NCT01143402) of patients with metastatic uveal melanoma

PURPOSE: Clinical trials commonly use physician-adjudicated adverse event (AE) assessment via the Common Terminology Criteria for Adverse Events (CTCAE) for decision-making. Patient-reported health-related quality of life (HRQoL) data is becoming more frequent in oncology; however, the relationship between physician-adjudicated AE assessment and HRQoL is understudied. METHODS: Data from a phase II trial (clinicaltrials.gov identifier: NCT01143402) where patients with metastatic uveal melanoma were randomized to receive selumetinib, an oral MEK inhibitor, or chemotherapy were analyzed. Patients reported HRQoL at baseline, after 1 month, and end of treatment (n=118), whereas physicians adjudicated AEs via CTCAE. Mean HRQoL scores were compared between patient randomization arms, as well as between those patients who did/did not receive dose modifications. RESULTS: Ninety-four percent had a CTCAE grade ≥ 1 for at least one treatment-associated AE, with 18% undergoing dose modification due to toxicity. Mean HRQoL scores did not significantly differ at each of the three time points. Patient and physician-adjudicated reports of nausea were significantly correlated at the start (r=0.31, p<0.01) and end of treatment (r=0.42, p<0.05). There were no significant correlations between need for dose modification and HRQoL scores. CONCLUSIONS: Despite the high rate of physician-adjudicated AEs and need for dose modifications with selumetinib, patient-reported HRQoL was not impacted by treatment. Since HRQoL did not differ in the subgroup of patients who received dosage reductions due to AEs, patients may be willing to tolerate select AEs without dose modification (if medically appropriate). More research is needed to determine how to best integrate HRQoL data into clinical trial conduct

Gecombineerde ondersteuning in Ontmoetingscentra voor mensen met dementie en hun mantelzorgers vergeleken met reguliere dagbehandeling

BACKGROUND: A previous study in Amsterdam showed that combined family support in the Meeting Centres Support Programme, in which persons with dementia patients and their carers are both supported by one professional staff, is more effective in influencing behaviour problems and mood of dementia patients living in the community than non-integrated support, such as day care only. A multi-centre implementation study tests if similar effects are achieved in other regions of The Netherlands. METHODS: A pretest-posttest control group design was applied. 112 dementia patients who visited psychogeriatric day care in eight community centres across the country and in three nursing homes, and their carers participated in the study. The patients in the experimental group (n=89) received support from the Meeting Centres Support Programme together with their carers, while the control group (n=23) received day care only. Behaviour problems (aggressive behaviour, inactivity, non-social behaviour) and mood (dissatisfaction, depressive behaviour) were assessed using standardized observation scales. Quality of life was assessed by interviewing the patients. RESULTS: After 7 months the Meeting Centres Support Programme, compared to regular day care, showed a moderately positive effect on the degree of total behaviour problems (effect size=0.52), especially on inactivity (effect size=0.37) and non-social behaviour (effect size=0.60), a large effect on depressive behaviour (effect size=0.92) and a moderate effect on self-esteem (effect size=0.43). CONCLUSIONS: The Meeting Centres Support Programme proves to be more effective than regular day care in influencing behaviour problems, especially inactivity and non-social behaviour, and depressed mood. Participation in the programme also seems to have a positive effect on self-esteem, an important aspect of quality of life. These findings surpass the results of the Amsterdam study and confirm the surplus value of the Meeting Centres Support Programme as compared to regular day care for people with mild to severe dementi

BrafV600E cooperates with Pten loss to induce metastatic melanoma

Mutational activation of BRAF is the earliest and most common genetic alteration in human melanoma. To build a model of human melanoma, we generated mice with conditional melanocyte-specific expression of BRaf(V600E). Upon induction of BRaf(V600E) expression, mice developed benign melanocytic hyperplasias that failed to progress to melanoma over 15-20 months. By contrast, expression of BRaf(V600E) combined with Pten tumor suppressor gene silencing elicited development of melanoma with 100% penetrance, short latency and with metastases observed in lymph nodes and lungs. Melanoma was prevented by inhibitors of mTorc1 (rapamycin) or MEK1/2 (PD325901) but, upon cessation of drug administration, mice developed melanoma, indicating the presence of long-lived melanoma-initiating cells in this system. Notably, combined treatment with rapamycin and PD325901 led to shrinkage of established melanomas. These mice, engineered with a common genetic profile to human melanoma, provide a system to study melanoma's cardinal feature of metastasis and for preclinical evaluation of agents designed to prevent or treat metastatic disease