Maximising the efficiency of clinical screening programmes: balancing predictive genetic testing with a right not to know

We explored the dilemma between patients'' right not to know their genetic status and the efficient use of health-care resources in the form of clinical cancer screening programmes. Currently, in the Netherlands, 50% risk carriers of heritable cancer syndromes who choose not to know their genetic status have access to the same screening programmes as proven mutation carriers. This implies an inefficient use of health-care resources, because half of this group will not carry the familial mutation. At the moment, only a small number of patients are involved; however, the expanding possibilities for genetic risk profiling means this issue must be addressed because of potentially adverse societal and financial impact. The trade-off between patients'' right not to know their genetic status and efficient use of health-care resources was discussed in six focus groups with health-care professionals and patients from three Dutch university hospitals. Professionals prefer patients to undergo a predictive DNA test as a prerequisite for entering cancer screening programmes. Professionals prioritise treating sick patients or proven mutation carriers over screening untested individuals. Participation in cancer screening programmes without prior DNA testing is, however, supported by most professionals, as testing is usually delayed and relatively few patients are involved at present. Reducing the number of 50% risk carriers undergoing screening is expected to be achieved by: offering more psychosocial support, explaining the iatrogenic risks of cancer screening, increasing out-of-pocket costs, and offering a less stringent screening programme for 50% risk carriers.     

ANDROGENETIC ALOPECIA IN MEN: THE SCALE OF THE PROBLEM AND PROSPECTS FOR TREATMENT

While the precise incidence of androgenetic alopecia is unknown, it is universally acknowledged to be the most common hair problem in men. Balding is generally associated with ageing; consequently, the desire to prolong a youthful appearance inevitably leads to demands for effective treatments. Further, changing attitudes in modern society have resulted in people becoming concerned about their appearance and less tolerant about conditions that might be alleviated by medical intervention. The importance of hair loss upon quality of life has been underestimated by the medical profession. Clinicians failing to accept hair loss as an important medical problem ignore the real distress suffered by a significant proportion of those affected. New options for treatment that selectively target the metabolic pathways involved in the balding process are showing promise. The first generation of such drugs, Propecia, is now available in some countries and other molecules are currently under development.     

The effect of treatment preference and treatment allocation on patients’ health-related quality of life in the randomized EMMY trial

Objectives

To determine the effect of preference and treatment allocation on health-related quality of life (HRQOL) in patients in the randomized EMMY trial of hysterectomy versus uterine artery embolization (UAE) for symptomatic uterine fibroids.

Study design

We invited 349 patients eligible for trial participation, of which 177 agreed to participate (the ‘randomized group’). Within the randomized group, patients were allocated to.UAE (n = 88) or hysterectomy (n = 89). The remaining 172 patients refused randomization and received the treatment of their preference (varying from hysterectomy to no treatment at all), of which 103 patients agreed to fill in questionnaires (the ‘preference group’). Patients’ treatment preferences and HRQOL were assessed at baseline and the patients were prospectively followed to evaluate HRQOL at 12 months after treatment.

Results

At baseline, most patients in the randomized group preferred UAE: 115/177 (65%). In the preference group most patients preferred hysterectomy: 100/172 (58%). At 12 months there was no effect of having had the preferred treatment on HRQOL, neither in the randomized nor in the preference group. The randomized group improved significantly in both mental and physical health, compared to baseline. In the preference group, only mental health improved compared to baseline, while physical health did not improve significantly.

Conclusions

In a randomized trial comparing UAE and hysterectomy for symptomatic fibroids, the pre-randomization preference for a specific treatment did not affect HRQOL.Trial participants improved better on physical HRQOL than women who refused to participate.     

3，4－二羟基苯乙酮对老年大鼠血小板膜磷脂成分的影响

ＤＨＡＰ１００ｍｇ·ｋｇ－１·ｄ－１，ｐｏ，持续１０周，可使老龄大鼠血小板膜磷脂（ＰＬ）含量增加，膜磷脂与膜胆固醇比值（ＰＬ／Ｃ）相对增高；血小板磷脂成分——磷脂酰乙醇胺（ＰＥ）和磷脂酰胆碱（ＰＣ）含量也有明显增加（ｐ＜０．０１），但血小板膜总脂及膜胆固醇含量无明显变化（Ｐ＞０．０５）。本实验结果提示：ＤＨＡＰ对血小板功能的影响可能与其抑制血小板膜磷脂降解、改变血小板膜组分有关。     

Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers.

BACKGROUND: Mutations of the tumor suppressor gene p53 have been identified in breast cancer cell lines, and some breast carcinomas are detectable by immunohistochemical assay because of p53 protein accumulation. PURPOSE: This study was designed to determine whether p53 protein accumulation in breast cancers correlates with p53 gene mutation, with survival, and with five pathobiologic factors associated with prognosis. METHODS: IgG1 monoclonal antibody to human p53 protein (PAb 1801) and immunohistochemical methods were used to detect p53 protein accumulation in archival formalin-fixed, paraffin-embedded, randomly selected carcinomas. We studied 295 invasive ductal carcinomas from the Massachusetts General Hospital; 151 were determined to be sporadic (not hereditary). We also studied 97 invasive ductal carcinomas--21 sporadic and 76 familial (hereditary)--from Creighton University. In addition, we examined 31 archival in situ carcinomas, 15 snap-frozen invasive ductal carcinomas, primary cell cultures from three benign breast tissue samples, and breast carcinoma cell lines MDA-MB-231 and MDA-MB-468. RESULTS: Nuclear p53 protein was observed in 16% of the 31 in situ carcinomas, 22% of the 172 sporadic carcinomas, 34% of the 50 tumors from patients with familial breast cancer, 52% of the 23 tumors from patients with the familial breast and ovarian cancer syndrome, and all three tumors from two patients with the Li-Fraumeni syndrome. There was complete concordance between p53 gene mutation and p53 protein accumulation in the 15 snap-frozen carcinomas and in both breast carcinoma cell lines. Statistically significant associations of p53 protein accumulation with estrogen receptor negativity and with high nuclear grade were found. There were statistically significant associations, independent of other prognostic factors, between p53 protein accumulation and metastasis-free and overall survival, for randomly accrued and for both sporadic and familial tumors. CONCLUSIONS: Immunohistochemically detected p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation and p53 gene mutation.