Healthy-year equivalents in major joint replacement. Can patients provide meaningful responses?

OBJECTIVES: Healthy-years equivalents (HYEs) have been proposed as an evaluative measure with advantages over quality-adjusted life-years (QALYs). The main purpose was to assess the feasibility of eliciting HYEs from patients who have undergone major joint replacement; a secondary objective was to examine relationships with postsurgical health status. METHODS: Pre- and postsurgical reports of perceived comorbidity and current arthritic burden were obtained from 194 patients, using a comorbidity checklist, summary scores from the Western Ontario/McMaster Osteoarthritis Questionnaire (WOMAC), summary scores derived from six Likert scales, and holistic utility scores for the same attributes. After surgery, HYEs for the full across-time health profile were also elicited. RESULTS: All measures of arthritic burden were sensitive to pre/postsurgical changes (p = .0001), and comorbidity scores were stable. Two HYE subgroups emerged. An HYE-invariant subgroup ascribed full HYEs to their profiles, while reporting higher Likert (t = 2.1309; p = .0344) and utility (s = 4.1504; p = .0001) scores for their postsurgical health state. An HYE-variant subgroup reported HYEs that were weakly but significantly (p < .009) correlated with Likert (r = .30), utility (rs = .25), and comorbidity (r = -.26) scores for their postsurgical state. CONCLUSIONS: Our results indicate that patients can understand the HYE assessment procedures and provide interpretable responses. However, a significant proportion reports invariant HYEs that could inflate estimates of the overall mean HYE. Further exploration of the HYEs reported by different clinical and attitudinal populations is needed before widespread adoption of this measure.     

Building an inter-disciplinary science of health inequalities: the example of lifecourse research

Across the post-industrial world, new public health strategies are being developed with the goal of reducing the socio-economic gradient in health. These new strategies are distinguished by a commitment to tackling the macro determinants of health inequalities through policies informed by scientific evidence. The engagement with macro determinants and with scientific evidence presents a major challenge to the health inequality research community. This is not only because of the complexity of the links between distal causes, proximal risk factors and health outcomes. It is also and more importantly because of the narrow disciplinary base of health inequality research. Grounded in social epidemiology, health inequality research has illuminated the pathways which run from individual socio-economic position to health-but has left in shadow the factors which influence socio-economic position. Broadening the evidence base to include these structural processes requires a new science of health inequalities, resourced both by epidemiological research and by research on social inequality and social exclusion. The paper demonstrates how such an inter-disciplinary science can be constructed. Taking lifecourse research as its example and the UK as its case study, it nests epidemiological research within social policy research: setting evidence on the health consequences of cumulative exposures within research on lifecourse dynamics, and locating both within analyses of how state policies can amplify or moderate inequalities in socio-economic position.     

Carers' experiences of hospital discharge and continuing care in the community

This paper presents the findings of a study of carers' perspectives on discharge procedures and continuing care arrangements for adults aged 18–65 with physical and complex disabilities. Interviews were conducted with carers of people discharged from younger disabled units (YDUs) and hospital settings. The emphasis carers place on the need to be informed and involved in the discharge planning process is described, and the adequacy of continuing care arrangements from carers' perspectives is examined. The findings of the study raise issues for policy and practice about carers' needs, vis-à-vis patients, to be included as active participants in the discharge planning process.     

Tyrosine nitration in blood vessels occurs with increasing nitric oxide concentration.

1. Experiments were designed to explore the effects of nitric oxide (NO) donors on generation of superoxide (O2.-) and peroxynitrite (ONOO-) in rabbit aortic rings. 2. Following inhibition of endogenous superoxide dismutase (SOD), significant basal release of O2.- was revealed (0.9 +/- 0.01 x 10(-12) mol min-1 mg-1 tissue). Generation of O2.- increased in a concentration-dependent manner in response to NADH or NADPH (EC50 = 2.34 +/- 1.18 x 10(-4) and 6.21 +/- 1.79 x 10(-3) M respectively, n = 4). NADH-stimulated O2.- chemiluminescence was reduced by approximately 85% in the presence of exogenous SOD (15 x 10(3) U ml-1). 3. Incubation of aortic rings with S-nitrosoglutathione (GSNO; 1 x 10(-5)-3 x 10(-3) M) or sodium nitroprusside (SNP; 1 x 10(-8)-1 x 10(-3) M), resulted in a concentration-dependent quenching of O2.- chemiluminescence which was proportional to NO release. 4. ONOO- formation was assessed indirectly by determining protein tyrosine nitration in rabbit aorta using a specific antibody against nitrotyrosine. Basally and in the presence of NADH, a single band was detected. Incubation of aortic rings with either GSNO (1 x 10(-3) M) alone or GSNO with NADH resulted in the appearance of additional nitrotyrosine bands. Incubation of serum albumin with GSNO alone did not cause nitrotyrosine formation. In contrast, incubation with 3-morpholinosydonomine (SIN-1; 1 x 10(-3) M, 10 min), resulted in marked nitration of albumin which was reduced by oxyhaemoglobin or SOD. Incubation of albumin with GSNO and pyrogallol, a O2.- generator, also resulted in protein nitration. 5. Addition of exogenous NO results in nitrotyrosine formation in rabbit aortic rings. Nitrotyrosine formation is likely to result from the reaction of exogenous NO and basal endogenous O2.- resulting in the formation of ONOO-. Formation of ONOO- and nitration of tyrosine residues potentially could lead to vascular damage and might represent unexpected adverse effects of long-term nitrate therapy.     

Effect of two antiprogestins (mifepristone and onapristone) on endometrial factors of potential importance for implantation

Objective: To investigate the effects of postovulatory administration of antiprogestins on endometrial factors that may be of importance for successful implantation.

Design: Ten women were given 200 mg mifepristone and an additional 10 women 400 mg of onapristone 48 hours after the LH surge in urine (LH+2).

Main Outcome Measure(s): Biopsies were assessed for histologic dating and the immunolocalization of [1] leukemia inhibitory factor,[2] 15-hydroxyprostaglandin dehydrogenase, and [3]the cell proliferation marker Ki 67. Hormonal measurements in blood and urine were used to monitor the effects on the ovarian cycle. Glycodelin (placental protein 14) concentrations were measured in blood taken on LH±12.

Result(s): Treatment with antiprogestins retarded the development of secretory changes without affecting the length of the luteal phase. In addition, there was reduced immunostaining for 15-hydroxyprostaglandin dehydrogenase within glands and a significant reduction in serum levels of glycodelin. Reduced immunostaining for leukemia inhibitory factor also was apparent within glands in biopsies taken on LH+6 of the treatment cycle. Increased Ki 67 immunostaining was observed on both cycle days after treatment, consistent with P antagonism.

Conclusion(s): Administration of mifepristone and onapristone adversely affects uterine receptivity. This adds further evidence to support their potential as a method of postovulatory fertility control.     

A multistep model for ovarian tumorigenesis: the value of mutation analysis in the KRAS and BRAF genes

Epithelial ovarian tumours represent a complex group of histological subtypes and there has long been controversy over the question of a precursor lesion for these neoplasms. The application of mutation analysis of the KRAS and BRAF genes (members of the RAS-RAF-MEK-ERK-MAP kinase pathway) is consistent with the model for progression of mucinous carcinomas and a subset of serous carcinomas (the so-called low-grade serous carcinomas) through benign and borderline lesions. The relatively high incidence of BRAF and KRAS mutations in serous borderline tumours and low-grade serous carcinomas, and their extremely low incidence/absence in high-grade serous carcinomas, provide strong evidence that high-grade carcinomas do not arise through this intermediate step.     

Monoclonal antibody detection of a circulating tumor-associated antigen. I. Presence of antigen in sera of patients with colorectal,gastric, and pancreatic carcinoma

Hybridoma-secreted monoclonal anti-colorectal carcinoma antibodies 19-9, 52a, and C₄ 14 bind specifically to cells of colorectal, gastric, and pancreatic carcinoma in tissue culture. The assay for the detection of antigen in human sera is based on the inhibition of binding of monoclonal antibodies to target preparations of colorectal carcinoma cells. Binding of monoclonal antibody 52a was inhibited more than 12% by 163 of 255 sera from patients from various stages of carcinoma of colon and rectum, by 45 of 49 sera from patients with pancreatic carcinoma, and by 8 of 11 sera from patients with gastric carcinoma. By contrast, only 7 of 89 sera from patients with other malignancies and 2 of 108 sera from healthy donors inhibited binding of this monoclonal antibody by more than 12%. These studies show the potential usefulness of monoclonal antibodies in the diagnosis of human malignancy.