9003 Background: HD IL-2 remains one of two FDA-approved therapies for the treatment of patients (pts) with advanced melanoma. Initial studies conducted 15–20 years ago reported 16% response rate with 8% of pts achieving durable responses. The toxicity of HD IL-2 limits its application to pts treated in specialized centers. We present the clinical outcome of pts treated over a recent 2 year period with HD IL-2 at a single institution and an associated retrospective pilot study evaluating the predictive value of a novel tumor gene expression signature. Methods: Clinical and radiological data were collected and analyzed on 49 consecutive pts treated with HD IL-2 at Beth Israel Deaconess Medical Center from 10/05 - 10/07. Response was evaluated via RECIST. Formalin-fixed paraffin embedded tumor was obtained on consenting pts and classified as either Class 1, defined by melanocyte-specific genes including MITF, or Class 2, represented by immune genes, using the DNA-mediated Annealing, Selection, and Ligation (DASL) technique. Two-sided Fisher's Exact test was used to compare the proportion of responses for pts in the two classes. Results: Clinical response occurred in 16 of the 49 pts (32.6%), with 5 pts (10.2%) having a CR. Two other pts had stable disease > 12 mos; 3 pts who progressed after response had resection to NED. 10 pts remain disease/progression free at a minimum of 16 mos following treatment. 28 pts (including 13 of 16 responders) had sufficient tumor for DASL analysis. Among the 21 categorized as Class 1, 7 (33%) were responders. Of the 7 classified as Class 2, 6 (86%) were responders. This difference in response was statistically significant (p = 0.0286). Conclusions: The overall and CR rates in a contemporary series of pts with metastatic melanoma treated with HD IL-2 are twice that reported in initial studies suggesting some treatment selection on clinical grounds since the 1990s. Pts with tumors expressing an immune signature by DASL appeared more likely to respond. This finding requires prospective validation, but suggests immune-related gene expression might contribute to IL-2 responsiveness. [Table: see text]
AbstractEpidemiological studies among migrant ethnic groups are potentially important as a way to provide insight into the relative importance of genetic, cultural, and socioeconomic factors in the etiology of substance use disorders. This paper summarizes prior United Kingdom studies of the prevalence of substance-use-associated problems in different ethnic groups before analyzing trends in recent mortality data by country of birth. On this evidence, rates of alcohol-related mortality may be marginally higher for those born in the Caribbean than for the native British, but are substantially raised for those born in Ireland and the Indian subcontinent. There is some indication that rates for the Caribbean and possibly the Irish groups have risen more rapidly than for the national population over a 12-year period. These differences in mortality rates seem to have arisen for complex reasons. [Translations are provided in the International Abstracts Section of this issue.]Key Words: EthnicityAlcohol-related mortalityEngland and Wales
This study investigated the influence of ‘cognitive busyness’ (competing cognitive demands) on residential care staff attributions of challenging behaviour (CB) related to dementia. Following the model of attribution formation proposed by Gilbert, Pelham, and Krull (1988), it was hypothesised that care staff experiencing competing cognitive demands at the time of observing CBs linked with dementia would be more likely to make internal and controllable attributions regarding the causes of such behaviour. This study employed a cross-over experimental design. Thirty formal dementia care-workers viewed two video clips of simulated CB, one under conditions of cognitive ‘busyness’ and another under control conditions of no extra cognitive demands. These conditions occurred a week apart and were counterbalanced, i.e. one group of participants undertook the control condition first and then the experimental condition whilst another undertook the reverse. Self-report measures of attributions were administered after the viewing of each video clip. Competing cognitive demands significantly influenced staff attributions regarding CB, in relation to internality and controllability, and type of CB emerged as a potential moderating factor. No link was found between cognitive busyness and other attributional dimensions (stability and globality). Concurrent cognitive demands seem capable of impairing the ability to use situational information to form some causal attributions regarding CB in dementia but this might depend on the type of CB being witnessed. The results are discussed in relation to key methodological and conceptual issues.
Abstract Background The aims of this study were to identify factors that influence the risk of stroke or death following carotid endarterectomy (CEA) and to develop a model to aid in comparative audit of vascular surgeons and units. Methods A series of 839 CEAs performed by four vascular surgeons between 1992 and 1999 was analysed. Multiple logistic regression analysis was used to model the effect of 15 possible risk factors on the 30-day risk of stroke or death. Outcome was compared for four surgeons and two units after adjustment for the significant risk factors. Results The overall 30-day stroke or death rate was 3·9 per cent (29 of 741). Heart disease, diabetes and stroke were significant risk factors. The 30-day predicted stroke or death rates increased with increasing risk scores. The observed 30-day stroke or death rate was 3·9 per cent for both vascular units and varied from 3·0 to 4·2 per cent for the four vascular surgeons. Differences in the outcomes between the surgeons and vascular units did not reach statistical significance after risk adjustment. Conclusion Diabetes, heart disease and stroke are significant risk factors for stroke or death following CEA. The risk score model identified patients at higher risk and aided in comparative audit.
Aims and objectives To identify sources of information and support preferred by young people to understand adolescent practices as adolescents develop a sexual health knowledge base. Background Statistics suggest that adolescents are not always making safe sexual health decisions. It is essential to develop an understanding of preferred sources of information and support to structure health and education services so that adolescents develop skills and knowledge to make safer choices. Design A cross‐sectional survey design. Methods A wide‐ranging questionnaire was developed using validated questions, drawn from similar adolescent lifestyle surveys and adapted with guidance from an advisory group; 2036 13–16‐year‐olds responded. Two questions, reporting information sources adolescents find useful and sources of approachable support, are considered here. Results Adolescents find informal sources more useful and experience higher levels of comfort accessing informal support especially from their best friends and mothers. Of formal provision, school‐based sources are preferred; however, sexual health information seeking is gendered and changes across year groups. The range of sexual health information sources adolescents access increases with age, and how they access these information sources changes as sexual activity increases and the information becomes more relevant. Conclusions The findings support the targeting of sexual health provision in relation to age and gender and suggest a youth‐focused approach to formal provision, including outreach working and a collaborative relationship with adolescents and parents. Relevance to clinical practice The findings contribute to an understanding of sources of information and support preferred by adolescents. In particular, they need to reconsider how services external to the school may be developed so they are youth‐focused and approachable. Nurses need to consider how best to work in partnership with adolescents and their families to disseminate accurate information and develop relevant services.
Aims: The current study evaluated the long-term effectiveness of a multi-disciplinary approach to chronic fatigue syndrome/myalgic encephalopathy (CFS/ME) in a UK outpatient service. Methods: A longitudinal questionnaire survey was posted to 300 patients, incorporating measures of fatigue, physical functioning, mental health, and pain. Outcome measures administered at baseline (prior to service use) were compared to assessments at discharge, and at follow-up (average 34 months post-intervention). Results: Linear mixed modelling showed that fatigue, physical functioning, and depression significantly improved, although the improvement was reduced for fatigue, physical functioning, and pain at follow-up. Gainful employment had a significant positive association with most measures. Conclusions: The targeted multi-disciplinary service appeared to be at least somewhat effective long-term, and highly acceptable to patients. Patients appeared to benefit from individual and group approaches that combined cognitive behavioural therapy, graded exercise therapy, and pacing.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
