Cost effectiveness of newborn screening for cystic fibrosis: a simulation study.

BACKGROUND: Early detection of cystic fibrosis (CF) by newborn screening (NBS) reduces the rate of avoidable complications. NBS protocols vary by jurisdiction and the cost effectiveness of these different protocols is debated. OBJECTIVE: To compare the cost effectiveness of various CF NBS options. METHODS: A Markov model was built to simulate the cost effectiveness of various CF-NBS options for a hypothetical CF-NBS program over a 5-year time horizon assuming its integration into an existing universal NBS program. NBS simulated options were based on a combination of tests between the two commonly used immunoreactive trypsinogen (IRT) cutoffs (96th percentile and 99.5th percentile) as first tier tests, and, as a second tier test, either a second IRT, pancreatic-associated protein (PAP) or CFTR mutation panels. CFTR mutation panels were also considered as an eventual third tier test. Data input parameters used were retrieved from a thorough literature search. Outcomes considered were the direct costs borne by the Quebec public health care system and the number of cases of CF detected through each strategy, including the absence of screening option. RESULTS: IRT-PAP with an IRT cutoff at the 96th percentile is the most favorable option with a ratio of CAD$28,432 per CF case detected. The next most favorable alternative is the IRT1-IRT2 option with an IRT1 cutoff at the 96th percentile. The no-screening option is dominated by all NBS screening protocols considered. Results were robust in sensitivity analyses. CONCLUSION: This study suggests that NBS for cystic fibrosis is a cost-effective strategy compared to the absence of NBS. The IRT-PAP newborn screening algorithm with an IRT cutoff at the 96th percentile is the most cost effective NBS approach for Quebec.

[Assessment of mammography screening and its introduction in Germany in the Statutory Early Diagnosis Program]. / Wissensstand zum Mammographie-Screening zur Einführung in Deutschland in das gesetzliche Früherkennungsprogramm.

Malmö, in the south of Sweden, has, over the past 15 years, achieved a reduction in the mortality rate of 10% as a result of adjuvant drug treatment (adjuvant chemo- and hormone therapy). The drop in the mortality rate by means of a quality assured early diagnosis programme, reduces the mortality rate for breast cancer by 34% so that in South Sweden these methods have reduced the death rate for breast cancer by a total of 44% although the incident rate has increased by 1.25%. It follows that a quality assured early diagnosis programme is by far the most effective method of reducing the mortality rate for breast cancer, whereby breast cancer constitutes the main cause of death from cancer in women. The effectiveness of early diagnosis is dependent on experience with these methods whereby the learning curve, even in the case of specialists, does not reach a maximum until there has been at least 6-8 years experience and a minimum of 8000 patients have been seen. A reduction in the mortality rate can only be achieved if a large number of the population takes part (in Sweden, 89% of women contacted) and only applies to the age group 40-70. In the case of younger women (40-50 years) the reduction in the death rate in Sweden lies at 30%. For cost-benefit reasons this age group has not yet been recommended for routine screening in Sweden, apart from in clinical studies. Screening is only effective with complete quality control of technical equipment and personnel as stipulated in the European guidelines for screening mammography (August 1997 edition, EU Commission (EUREF). The risks of radiation exposure, with a threshold value of 5 mGy per breast (X-ray in two planes), is so minimal that it is as yet not measurable. The induction of breast cancer through annual screening mammography is estimated theoretically at 4 indicated cases of breast cancer to 1 million female years. Theoretically these induced cases of breast cancer can be cured by early diagnosis. A reduction in the mortality rate of 34% is a tremendous advantage for women. Since breast cancer is the main cause of death in women between the ages of 38 and 51 and screening considerably cheaper than other preventive measures (cervical smear, dialysis in kidney disease, safety belts, medication to lower cholesterol levels) the introduction of quality assured screening is an essential priority towards improving the health of women in society today. It has been proved (Netherlands) that the cost of screening is far lower than the expense incurred in the treatment of women in the metastatic stage of their cancer illness before death.

[Cost-benefit analysis in mammography screening]. / Kosten-Nutzenanalyse beim Mammographie-Screening.

The Swedish Mammography-Screening trials have shown a long-term reduction in the mortality rate in women aged between 50-69 of up to 30%. The lower reduction in mortality observed in women aged 40-49 was not statistically significant. Long-term observation over 20 years) has shown that a radiation dose of 2.4 mGy for a 2-view-mammography per breast does not lead to an increase in occurrence of breast cancers. The advantage of screening with regard to a reduction in death rate, frequent use of breast cancerving therapy and the reduction by half in the average size of the tumor compared to control groups results in: A recommendation for quality controlled screening in Germany from the age of 50 to 70. The possible advantage for younger women must be examined in further trials. Screening in the form of a de-centralized check-up system is to be carried out by practising doctors in co-operation with hospitals which will be responsible for double findings, assessment of difficult cases and continuous cost evaluation. Quality assurance centres, reference and training centres are required. The mammography in curative check-ups will also benefit from a screening programme.

Breast tumors: computer-assisted quantitative assessment with color Doppler US.

PURPOSE: To compare quantified measurements with color Doppler ultrasonography (US) with those obtained with conventional duplex US in the differential diagnosis of suspect lesions in the breast. MATERIALS AND METHODS: A computer-assisted protocol was used to calculate the color pixel density (CPD) and the mean color value (MCV) in US images of breast lesions. These results were compared with conventional results in the examination of 25 patients (aged 29-78 years) with carcinomas and 32 patients (aged 23-73 years) with benign lesions of the breast. RESULTS: The sensitivity of maximum flow velocity in helping identify carcinomas was 60% and the specificity was 70%. In color Doppler US, the sensitivity for MCV in helping identify carcinomas was 92% and the specificity was 78%; for CPD the sensitivity was 64% and the specificity was 91%. Combining MCV and CPD did not improve differentiation. CONCLUSION: Computer-assisted image analysis may be superior to conventional duplex US in helping differentiate between carcinomas and benign lesions.

Loss of brain 5-HT2 receptors in Alzheimer's disease. In vivo assessment with positron emission tomography and [18F]setoperone.

Using [18F]setoperone and positron emission tomography (PET), alterations in serotonergic 5-HT2 receptor binding were studied in cerebral cortex of nine unmedicated patients with probable Alzheimer's disease and 37 healthy controls. The kinetics of unchanged radioligand in plasma and 18F-radioactivity in blood and brain were obtained for 90 min following tracer injection. The specific binding of [18F]setoperone to 5-HT2 receptors in the cerebral cortex was quantitated by subtraction using cerebellum as reference. In controls, a significant reduction in specific binding was associated with age and similar linear regression slopes were obtained in all the cortical regions studied. No significant difference was observed between patients with Alzheimer's disease and age-matched controls in the injected mass of setoperone, percentage of unmetabolized [18F]setoperone in plasma, 18F-radioactivity in blood fractions and cerebellar 18F-radioactivity concentration, indicating similar non-specific brain kinetics and metabolism of the radioligand. In contrast, there was a significant reduction in specific [18F]setoperone binding in the cerebral cortex in patients with Alzheimer's disease relative to control values (temporal, 69%; frontal, 69%; parietal, 55%; temporo-parietal, 54%; occipital cortex, 35%). The results demonstrate that the loss in 5-HT2 receptor binding in the cerebral cortex of patients with Alzheimer's disease, long documented by post-mortem studies, can now be assessed in vivo using PET.

Mammographic assessment of human breast cancer growth and duration.

BACKGROUND: Accumulating data from numerous sources have confirmed that breast cancers have highly variable rates of growth. Contemporary thought supports that collectively the gross rates should decelerate with increasing tumor mass. METHODS: Using composite data derived from mammographically measured growth of breast cancers observed at the Universities of Heidelberg and Louisville, the growth curve providing the best fit to the observed data, and the variance occurring around this curve has been calculated. RESULTS: A generalized logistic equation provided the best fit, with a natural variance ranging from extremely rapidly growing to slowly growing cancer. These data do not cover the entire range of growth rates because cancers appearing acutely between mammograms were observed only once, and some breast cancers never grew. CONCLUSIONS: The highly variable decelerating growth rates of breast cancers are better but incompletely defined, and these rates are of value in considering screening strategies and prognosis.

Urodynamic assessment and lateral urethrocystography. A comparison of two diagnostic procedures for female urinary incontinence.

We compared urodynamic findings and results of lateral urethrocystography in 84 case. The aim of the study was to establish a possible correlation between anatomic findings and functional results. Clinically, a significantly greater increase in the normal axis of urethral inclination was noted in patients with a urodynamic diagnosis of stress incontinence than in patients with urge incontinence or for normal urodynamic findings. Lateral urethrocystography vis-à-vis urodynamic assessment proved to be a method having high sensitivity (91%) but low specificity. These two methods supply different but complementary data. Together with the patients' medical history, the assessment of their complaints, clinical vaginal examination, and clinical stress test, they offer valuable information for an efficient therapeutic concept.

Hormesis, Gompertz functions, and risk assessment.

A historical survey of the literature indicates that benefits derived from low doses of toxic substances have been reported over many centuries. Hippocrates, Paracelsus, Arndt, Schulz, and Hahnemann (founder of homeopathy) have all reported that low doses of toxic substances may be "stimulatory" or otherwise beneficial. Assessment of mortality data from modern-day bioassay studies indicates that low-dose animal exposure to a variety of toxic agents can, through an unknown mechanism, also induce beneficial changes which promote health and prolong life (longevity hormesis). This nonspecific and apparently reversible phenomenon has been modeled kinetically through use of age-specific mortality rate and a generalized Gompertz function; the basic assumption is that mortality in an interval is a function of the weighted sum of intensities of physiologic injury during that interval. It was assumed that longevity-enhancing hormetic reduction in population injury may be decremented from life-shortening injury produced through the aging process and concomitant toxicity. At low exposure levels, a net reduction in age-specific mortality rate can sometimes be observed. The implications for risk assessment are significant. It is tacitly assumed in generating virtually all estimates of risk that toxic manifestations observed at higher doses are the sole effects elicited at lower doses. This appears to be qualitatively incorrect.

The Quebec question: a matter of population.

PIP: Current demographic trends in Quebec are reviewed. The relative contribution of natural increase and migration to the province's population growth is assessed. Consideration is given to language, population reproduction, and demographic aging. The political, economic, and social consequences of these trends are discussed. (SUMMARY IN FRE)^ieng