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PubMed2006

[Biochips--tools of 21st century medicine].

In the next years biochips will enter into clinical medicine. Each larger diagnostics laboratory will offer genetic tests with this method. In this article the potential of biochips is shown by two examples: Differentiation and prognosis in breast cancer and individualized drug therapy (pharmacogenetics). In cancer the gene expression profile permits an accuracy of differentiation and prognosis that was impossible so far. Already soon oncologists will make their therapeutic decisions on the basis of biochip-based gene expression profiles. For an individualized drug therapy extensive genetic tests must be accomplished, above all of the cytochrome P450 system. An already available biochip seems to make this possible reliably and economically. Moreover, in science biochips will play a substantial role in the analysis of the genetic basis of common diseases. If these diseases are understood once, the clinical use of biochips will open an enormous potential for a predictive medicine. Biochips are a relevant topic for insurers--partially already today, much more however in the future.

Breast Neoplasms↗
PubMed2006

Pediatric liver transplant recipients: mortality analysis over 20 years.

Orthotropic liver transplantation (OLT) has become standard and accepted care for pediatric patients with end-stage liver disease. Two large pediatric OLT series are analyzed to determine excess death rates (EDR) over 20 years. The EDR decreases over time and is lower with more recent transplant recipients who have benefited from improved tacrolimus-based immunosuppression and transplant techniques. Fifteen- to 20-year EDR is 5 deaths/1000. Biliary atresia is the most common pediatric indication, and these recipients do better than those with other types of liver disease. Most deaths occur in the first post-transplant year, with infection being the largest cause.

Adolescent↗
PubMed2006

Mortality in a complete 4-year follow up of 85-year-old residents of Leiden, classified by serum level of thyrotropin and thyroxine.

BACKGROUND: The authors of the source article emphasize the clinical tendency to screen for, detect and treat for thyroid dysfunction in very elderly patients, in which it is a fairly common disorder, often with occult or no symptoms. Published evidence is conflicting on the benefit, if any, of such a program. Accordingly, they devised a prospective, population-based study to determine outcomes, including survival outcome, based on serum levels of thyroid-stimulating hormone (TSH) and thyroxine. METHODS: A cohort of 558 subjects who had their 85th birthday between September 1997 and September 1999 was enrolled after consent of the subject and screening examination that included serum TSH and thyroxine levels. This represented a 79% sample of all 85-year-old residents of Leiden, the Netherlands. Follow up was complete for survival 4 years to the subject's 89th birthday or prior death, although 70 subjects refused the annual re-examination. Thyroid function, disability, cognitive function and number of chronic diseases were analyzed, in addition to mortality, through Cox regression and other statistical methods. RESULTS: In 67 subjects with abnormally high TSH (>4.8 mIU/ L), the mean annual mortality rate was derived as 64 deaths per 1000 per year. In the 491 subjects with normal TSH or low TSH (<0.3 mIU/L), the mean annual mortality rate was derived at 114 per 1000 per year. Laboratory evidence of hypothyroidism (initially low serum thyroxine) was found in only 37 of the 67 subjects. CONCLUSION: In the 13% of elderly subjects in Leiden with abnormally high serum TSH levels, the mean annual mortality rate was significantly lower than the mortality rate in the 87% of the elderly patients with normal or low serum TSH. The significance is based on 95% confidence levels of the Poisson distribution. The rate in the group with high TSH levels had 16 deaths in 264 person-years of follow up (FU). The majority with normal or low TSH levels had 193 deaths in 1698 person-years of FU.

Actuarial Analysis↗
PubMed2006

Diabetes update.

The purpose of this article is to provide a general update of diabetes with a focus on newer developments that may impact risk assessment. The main reasons for concern about diabetes are the associated microvascular and macrovascular complications. Control of blood glucose levels, primarily assessed by measurement of hemoglobin A1c, has been shown to reduce the occurrence of microvascular complications. In conjunction with control of other risk factors, control of blood glucose levels reduces the occurrence of macrovascular complications. Type 1 diabetes is now known to be an autoimmune disease. For unknown reasons, the patient's immune system destroys its own pancreatic insulin-producing beta cells. The hallmark of type 2 diabetes is insulin resistance, which may be mediated by one of a number of gene defects. At some point, the pancreatic beta cells are unable to compensate for the insulin resistance by increasing insulin secretion. Type 2 diabetes then appears. Prediabetes, encompassing impaired fasting glucose and impaired glucose tolerance, is an important clinical entity that precedes the diagnosis of diabetes in many cases. Diet and exercise are the most important interventions for reducing the progression of insulin resistance to diabetes. Once diabetes develops, medications are matched to pathophysiology.

Blood Glucose↗
PubMed2006

Cost/benefit of laboratory tests.

BACKGROUND: Insurers choose laboratory test requirements to maximize the relationship between cost and benefit. Traditional means of analysis, such as experience studies, take years or decades to perform. Cost/benefit models provide a more timely option by projecting possible experience according to different scenarios. METHODS: The article describes how to create a cost/benefit model. RESULTS: Hemoglobin A1c and hepatitis C virus antibody tests--and more generally tests reflexed after a prior abnormal test--often have the highest cost/benefit ratio. Mortality savings is higher for tests done on older aged applicants (except for impairments that are more common in young people) and on tobacco users. Indirect costs, such as time, overhead, delays, and false positives, decrease the cost/benefit of testing. Entire markets may follow inefficient testing strategies because insurers do not deviate from the practices of market leaders. CONCLUSION: Cost/benefit analysis helps insurers set underwriting requirements by age, gender, tobacco/nontobacco status, and policy amount.

Clinical Laboratory Techniques↗