Marriage of a medium-term liver model to surrogate markers--a practical approach for risk and benefit assessment. (65/30946)

The need for a reliable medium-term alternative to traditional long-term rodent test protocols for carcinogen risk assessment is pressing given the immense variety of compounds being developed for introduction into the human environment. The established lack of a complete correlation between mutagenicity and carcinogenicity means that recourse must be made to an in vivo model. Optimally, this model should be able to detect not only complete carcinogenic or promoting potential but also any ability to inhibit neoplasia. In order to be effective, it must take into account the available detailed knowledge on mechanisms of action of carcinogens and modulating agents. The Ito model, for which a uniquely comprehensive set of background data has already been accumulated, has a solid scientific basis; this model utilizes quantitative data for glutathione S transferase-positive foci as the preneoplasia-based surrogate end point (PSE). A very practical candidate for routine application, its predictive power, its flexibility, and its capacity to incorporate a range of mechanism-based surrogate end points (MSEs) provide a powerful tool for attainment of the twin goals of detecting carcinogenic agents and identifying promising chemopreventors.  (+info)

An integrated assessment framework for climate change and infectious diseases. (66/30946)

Many potential human health effects have been hypothesized to result either directly or indirectly from global climate change. Changes in the prevalence and spread of infectious diseases are some of the most widely cited potential effects of climate change, and could have significant consequences for human health as well as economic and societal impacts. These changes in disease incidence would be mediated through biologic, ecologic, sociologic, and epidemiologic processes that interact with each other and which may themselves be influenced by climate change. Although hypothesized infectious disease effects have been widely discussed, there have not yet been thorough quantitative studies addressing the many processes at work. In part this is because of the complexity of the many indirect and feedback interactions or mechanisms that bear on all aspects of the climate issue. It also results from the difficulty of including the multitude of always-changing determinants of these diseases. This paper proposes a framework for an integrated assessment of the impacts of climate change on infectious diseases. The framework allows identification of potentially important indirect interactions or mechanisms, identification of important research gaps, and a means of integrating targeted research from a variety of disciplines into an enhanced understanding of the whole system.  (+info)

Audit of cardiac catheterisation in a district general hospital: implications for training. (67/30946)

OBJECTIVE: To assess complications of diagnostic cardiac catheterisation in a non-surgical centre by review of the first three years' experience and audit of 2804 diagnostic left heart procedures. DESIGN: Analysis of a prospective database of cardiac catheter procedures. SETTING: District general hospital without available on site cardiac surgery. RESULTS: The rate of major complications of cardiac catheterisation was 0.07%. Mortality was 0. 07%, and the rate of arterial complications (requiring surgical repair) was 0.24% for brachial arteries and 0.17% for femoral. These results are comparable to those reported from national and international surgical centres. CONCLUSION: A diagnostic cardiac catheterisation service can be offered in non-surgical hospitals without an increased risk to patients. It highlights the relevance of training in angioplasty and questions the appropriateness of starting preliminary invasive cardiology training of specialist registrars in district general hospitals.  (+info)

Is recruitment more difficult with a placebo arm in randomised controlled trials? A quasirandomised, interview based study. (68/30946)

OBJECTIVE: To investigate whether including a placebo arm in a clinical trial of hormone replacement therapy influenced women's stated willingness to participate. DESIGN: Quasirandomised, interview based study. SETTING: 10 group practices in the Medical Research Council's General Practice Research Framework. PARTICIPANTS: 436 postmenopausal women aged 45-64 who had not had a hysterectomy. MAIN OUTCOME MEASURES: Stated willingness to enter a trial and reasons for the decisions made. RESULTS: Of 218 women told about the trial without a placebo arm, 85 (39%) indicated their willingness to enter compared with 65 (30%) of the 218 women told about the trial with the placebo arm (P=0.06). Part of this difference was due to explicit reluctance to take a placebo. Altruism and personal benefit were the reasons most frequently given for wanting to take part in a trial. The reasons most frequently cited for not wanting to take part were reluctance to restart periods, not wanting to take unknown or unnecessary tablets, or not wanting to interfere with present good health. CONCLUSION: For preventive trials the inclusion of a placebo arm may reduce patients' willingness to participate.  (+info)

Ready-made, recalibrated, or Remodeled? Issues in the use of risk indexes for assessing mortality after coronary artery bypass graft surgery. (69/30946)

BACKGROUND: Risk indexes for operative mortality after cardiac surgery are used for comparative profiling of surgeons or centers. We examined whether clinicians and managers should use an existing index without modification, recalibrate it for their populations, or derive a new model altogether. METHODS AND RESULTS: Drawing on 7491 consecutive patients who underwent isolated CABG at 2 Toronto teaching hospitals between 1993 and 1996, we compared 3 strategies: (1) using a ready-made model originally derived and validated in our jurisdiction; (2) recalibrating the ready-made model to better fit the population; and (3) deriving a new model with additional risk factors. We assessed statistical accuracy, ie, area under a receiver-operator characteristic curve (ROC); precision, ie, statistical goodness-of-fit; and actual impact on both risk-adjusted operative mortalities (RAOM) and performance rankings for 14 surgeons. The new model was slightly more accurate than the ready-made model (ROC, 0.78 versus 0.76; P<0.05), albeit not different from the recalibrated model (ROC, 0.77). The ready-made model showed poor fit between the predicted and observed results (P<0.001), leading to significant underestimation of RAOM (1.6+/-0. 2%) compared with the other strategies (2.5+/-0.2%; P=0.048). Remodeling also changed the performance rankings among half the surgeons with higher RAOM. CONCLUSIONS: Poorly calibrated risk algorithms can bias the calculation of RAOM and alter the results of surgeon-specific profiles. Any existing index used for risk assessment in cardiac surgery should be episodically recalibrated or compared with new models derived from local subjects to ensure that its performance remains optimal.  (+info)

Standardized lifetime risk. (70/30946)

The authors propose the use of two new standardized measures of risk, the standardized lifetime risk and the standardized number of years of life lost. These measures maintain the advantages of standardized rates but are more readily understood without special training. In this paper, standardizing weights based on 1992 data from England and Wales are provided, and the new measures are illustrated with a variety of examples. The new standardized rates are useful for examining trends over time; for comparing the impact of various diseases on public health; and for comparing rates of a given disease in several different countries. The authors think it is far more informative to say that 41 out of every 1,000 women die of breast cancer than to say that the standardized mortality rate is 51 per 100,000 women per year.  (+info)

Survival prediction of terminally ill cancer patients by clinical symptoms: development of a simple indicator. (71/30946)

BACKGROUND: Although accurate prediction of survival is essential for palliative care, no clinical tools have been established. METHODS: Performance status and clinical symptoms were prospectively assessed on two independent series of terminally ill cancer patients (training set, n = 150; testing set, n = 95). On the training set, the cases were divided into two groups with or without a risk factor for shorter than 3 and 6 weeks survival, according to the way the classification achieved acceptable predictive value. The validity of this classification for survival prediction was examined on the test samples. RESULTS: The cases with performance status 10 or 20, dyspnea at rest or delirium were classified in the group with a predicted survival of shorter than 3 weeks. The cases with performance status 10 or 20, edema, dyspnea at rest or delirium were classified in the group with a predicted survival of shorter than 6 weeks. On the training set, this classification predicted 3 and 6 weeks survival with sensitivity 75 and 76% and specificity 84 and 78%, respectively. On the test populations, whether patients survived for 3 and 6 weeks or not was predicted with sensitivity 85 and 79% and specificity 84 and 72%, respectively. CONCLUSION: Whether or not patients live for 3 and 6 weeks can be acceptably predicted by this simple classification.  (+info)

Should we clone human beings? Cloning as a source of tissue for transplantation. (72/30946)

The most publicly justifiable application of human cloning, if there is one at all, is to provide self-compatible cells or tissues for medical use, especially transplantation. Some have argued that this raises no new ethical issues above those raised by any form of embryo experimentation. I argue that this research is less morally problematic than other embryo research. Indeed, it is not merely morally permissible but morally required that we employ cloning to produce embryos or fetuses for the sake of providing cells, tissues or even organs for therapy, followed by abortion of the embryo or fetus.  (+info)