X-ray illumination of the ejecta of supernova 1987A.

When a massive star explodes as a supernova, substantial amounts of radioactive elements--primarily (56)Ni, (57)Ni and (44)Ti--are produced. After the initial flash of light from shock heating, the fading light emitted by the supernova is due to the decay of these elements. However, after decades, the energy powering a supernova remnant comes from the shock interaction between the ejecta and the surrounding medium. The transition to this phase has hitherto not been observed: supernovae occur too infrequently in the Milky Way to provide a young example, and extragalactic supernovae are generally too faint and too small. Here we report observations that show this transition in the supernova SN 1987A in the Large Magellanic Cloud. From 1994 to 2001, the ejecta faded owing to radioactive decay of (44)Ti as predicted. Then the flux started to increase, more than doubling by the end of 2009. We show that this increase is the result of heat deposited by X-rays produced as the ejecta interacts with the surrounding material. In time, the X-rays will penetrate farther into the ejecta, enabling us to analyse the structure and chemistry of the vanished star.

Genetic discrimination: perspectives of consumers.

In a study of the perceptions of 332 members of genetic support groups with one or more of 101 different genetic disorders in the family, it was found that as a result of a genetic disorder 25 percent of the respondents or affected family members believed they were refused life insurance, 22 percent believed they were refused health insurance, and 13 percent believed they were denied or let go from a job. Fear of genetic discrimination resulted in 9 percent of respondents or family members refusing to be tested for genetic conditions, 18 percent not revealing genetic information to insurers, and 17 percent not revealing information to employers. The level of perceived discrimination points to the need for more information to determine the extent and scope of the problem.

The effect of age and sex on cost of inpatient facility encounters among patients with multiple sclerosis.

OBJECTIVE: To explore the effect of age and sex on cost of all-cause and multiple sclerosis (MS)-related inpatient facility encounters. METHODS: Adult patients with an initial MS diagnosis were identified from a national managed-care database (IMS LifeLink Health Plans Database). The analysis included newly diagnosed MS patients with 12 months insurance eligibility before and after their first MS diagnosis. Inpatient facility encounters (stays) were analyzed for all-cause and MS-related events (ICD-9-CM = 340.XX), other demyelinating CNS disease (ICD-9-CM = 341.XX), rehabilitation (ICD-9-CM = V57.89), and a group of symptom-related diagnoses. Costs and length of stay were evaluated using a general linear model controlling for age and sex. RESULTS: A total of 57,236 patients met study criteria; 74.3% were female. Mean age for females was 45.5 years and for males it was 47.5 years. In total, 17.0% had an all-cause inpatient stay in the 360-day post index, and 3.2% had an in patient stay with a MS relapse-related diagnosis as primary discharge diagnosis. Additional MS-related diagnoses that led to inpatient stays included other demyelinating CNS disease (0.3%), symptom-related diagnoses (1.0%), and rehabilitation (1.1%). All-cause inpatient cost was higher for males vs females across all age groups; however, cost for females increased at a greater rate as age increased (p = 0.0007). Symptom-related inpatient cost was flat for males, was lower for females than males at an average age of 30, and was greater for females than males at an average age of 60 (p = 0.0199). Cost for MS inpatient stays ($11,931), other demyelinating CNS-related stays ($14,931), and rehabilitation ($23,643) did not differ by age and sex. The average cost for any MS-related relapse inpatient stay was $13,761 and varied with increasing age (p < 0.0001). CONCLUSION: Burden of illness for relapse among MS patients is substantial. Costs vary by age and sex depending on the discharge diagnosis. Inclusion of symptom-related and rehabilitation inpatient stays may account for an under-recognized proportion of total expenditures.

Autosomal dominant inheritance of Brachmann-de Lange syndrome.

A mother with mild phenotype and her severely affected son, both with classic manifestations of Brachmann-de Lange syndrome (BDLS), are described. This documented mother-to-child transmission supports the hypothesis of autosomal dominant transmission with intrafamilial variability. Known cases of BDLS with autosomal dominant inheritance are reviewed. Although most cases of BDLS are sporadic, a careful evaluation of parents of affected children is important for appropriate genetic counseling.

Valproic acid embryopathy: report of two siblings with further expansion of the phenotypic abnormalities and a review of the literature.

Fetal Valproate Syndrome (FVS) results from prenatal exposure to valproic acid (VPA). It is characterized by a distinctive facial appearance, a cluster of minor and major anomalies, and central nervous system dysfunction. In this study, two siblings who were exposed to monotherapy with VPA are described with documentation of long-term follow up. Both children had craniofacial findings, multiple systemic and orthopedic abnormalities, an overgrowth pattern, and developmental deficits. The literature from 1978-2000 is reviewed. A total of 69 cases that were solely exposed to VPA with adequate phenotypic description were identified. The clinical manifestations of FVS encompass a wide spectrum of abnormalities including consistent facial phenotype, multiple systemic and orthopedic involvement, central nervous system dysfunction, and altered physical growth. The facial appearance is characterized by a small broad nose, small ears, flat philtrum, a long upper lip with shallow philtrum, and micro/retrognathia. In this review, 62% of the patients had musculoskeletal abnormalities, 30% had minor skin defects, 26% had cardiovascular abnormalities, 22% had genital abnormalities, and 16% had pulmonary abnormalities. Less frequently encountered abnormalities included brain, eye, kidney, and hearing defects. Neural tube defects were seen in 3% of the sample. Twelve percent of affected children died in infancy and 29% of surviving patients had developmental deficits/mental retardation. Although 15% of patients had growth retardation, an overgrowth pattern was seen in 9%. The data from this comprehensive review especially the developmental outcome should be added to the teratogenic risk, that arises in association with the use of VPA during pregnancy.

Familial 10p trisomy resulting from a maternal pericentric inversion.

We report a familial recombination of a pericentric inversion of chromosome 10 resulting in 2 affected relatives who had 10p trisomy and 10q monosomy with the karyotypic abnormality designated rec(10) dup p,inv(10) (p11.2q26). Both of these individuals had the typical characteristics of 10p trisomy, however, at birth the proposita had mild facial anomalies suggesting that the distinct facial characteristics may be of postnatal onset in some cases. In addition, the proposita had gastroesophageal reflux causing severe anemia. The phenotype of our patients is compared to 41 patients with 10p trisomy reported in the literature.

Characterization of a supernumerary marker derived from chromosome 17 by microdissection in an adult with MR/MCA.

We describe a 38-year-old adult who has a supernumerary marker chromosome in 40% of metaphase cells which was identified by reverse in situ hybridization with a DNA probe made by microdissection to be derived from chromosome 17. The breakpoints are estimated by G-banding and fluorescence in situ hybridization (FISH) to consist of the region from 17p11.1 to proximal 17q21. The propositus displayed severe growth retardation, kyphoscoliosis, bilateral cataracts, severe calcaneovalgus deformity of the feet, dysmorphic facies, profound mental retardation, and multiple medical problems requiring ongoing medical management. These problems included a mitral valve prolapse with regurgitation, recurrent upper and lower respiratory tract infections, and severe respiratory insufficiency. The relatively long survival of this patient enabled us to describe the natural history of this rare chromosomal mutation.

Trisomy 7p resulting from 7p15;9p24 translocation: report of a new case and review of associated medical complications.

The authors report on a young girl with generalized developmental deficits originally thought to be caused by an unusual reaction to DPT vaccination. At the age of 4(1/2) years, chromosome analysis showed that the terminus of the short arm of chromosome 9 had extra material believed to originate from 7p terminus, thus she was considered to be trisomic for a segment of 7p and monosomic for a small portion of 9p [46,XX,der (9), t(7;9)(p15;p24)]. Ten years later, molecular cytogenetic testing using fluorescence in situ hybridization (FISH) confirmed that the extra chromosomal material represented partial trisomy 7p. The proposita had a high and large forehead, hypertelorism, and broad nasal bridge, findings seen in most individuals with trisomy 7p. Long-term follow-up showed the presence of hypothyroidism, obesity, and cerebral palsy. A review of all published cases of trisomy 7p with focus on associated complications suggests a well-defined pattern of abnormalities characterized by musculoskeletal, cardiovascular, neurological, genital, and ocular abnormalities in decreasing frequency. At least one-third of affected individuals died in infancy and close to half had severe mental retardation. FISH was essential in the confirmation of the cytogenetic abnormality and further delineation of the chromosomal disorder.

Interstitial deletion of 4p15.32p16.3 in a boy with minor anomalies, hearing loss, borderline intelligence, and oligodontia.

We describe an 11-year-old boy of Saudi origin with an interstitial deletion in the short arm of chromosome 4 (p15.32p16.3) as determined by G-banding and fluorescent in situ hybridization. His clinical manifestations were similar but not identical to previously reported cases of interstitial deletion in the same chromosomal region, and were not those associated with Wolf-Hirschhorn syndrome. The boy had normal facial characteristics, short stature, minor anomalies of hands and feet, amblyopia of the right eye, bilateral hearing loss, and hypotonia. On developmental testing, he had borderline intelligence, with a severe sensory integration and motor planning disorder, and severe deficits in the communication domain. In addition, he had severe oligodontia affecting his secondary dentition. This finding supports the presence of one or more genes involved in dentition in this chromosomal region.

De novo duplication of 17p [dup(17)(p12----p11.2)]: report of an additional case with confirmation of the cytogenetic, phenotypic, and developmental aspects.

We describe an apparent de novo duplication of bands 17p11.2 and p12. A comparison of the manifestations of a previously reported case with a similar karyotype [Magenis et al., Am J Med Genet 24:415-420 (1986)] and of our own case seems to indicate a characteristic pattern which includes prenatal and postnatal growth retardation, facial changes, club feet, and mild developmental deficits. The prominent facial changes are a relatively triangular face, downslanted palpebral fissures, malocclusion, and abnormal ears. In addition, this condition appears to be milder than other duplications of the short arm of chromosome 17, namely trisomy 17p and dup(17)(p11.2----cen).

Dyssegmental dysplasia Silverman-Handmaker type in a consanguineous Druze Lebanese family: long term survival and documentation of the natural history.

We report on a male infant born with clinical and radiographic evidence of a lethal form of dyssegmental dysplasia not comparable to Silverman-Handmaker type, who had a prolonged survival of more than eight months. He had ocular and central nervous system abnormalities which have not been previously described. His course included significant feeding and respiratory difficulties, severe physical and psychomotor retardation, and recurrent fever of unknown etiology believed to be of central origin. The relatively long survival of this infant enabled us to focus on the natural history of this rare syndrome. The infant was born to first cousin parents of Druze Lebanese origin supporting an autosomal recessive mode of inheritance for the condition. This is the first documentation of dyssegmental dysplasia Silverman-Handmaker type in a family of Druze Lebanese ethnicity.

Economic, clinical, and humanistic outcomes: a planning model for pharmacoeconomic research.

Medical, ethical, and societal concerns about costs, access, and quality of care are causing health care practitioners to consider a more comprehensive model for medical decision making. Consequently, interest in research to assess the outcomes of health care has been increasing. The purpose of this paper is to explicate a theoretical framework for identifying, collecting, and using outcomes data to assess the value of pharmaceutical treatment alternatives. Causal relationships between disease, health outcomes, and decisions about medical care interventions (eg, treatment with pharmaceutical products and services) are proposed to address limitations inherent in the traditional medical decision-making model. The Economic, Clinical, and Humanistic Outcomes (ECHO) model depicts the value of a pharmaceutical product or service as a combination of traditional clinical-based outcomes with more contemporary measures of economic efficiency and quality. This integrated approach provides a theoretical basis for considering potential trade-offs among economic, clinical, and humanistic variables in optimizing the allocation of health care resources. The ECHO model is a preliminary step to modeling outcomes from pharmaceutical treatments and services. Data collection instruments need to be developed, and the proposed relationships among outcomes variables should be established empirically. The ECHO model should assist health services researchers in planning, conducting, and evaluating pharmaceutical products and services from a multidimensional perspective.

A comparison of costs and efficacy of intranasal fluticasone propionate and terfenadine tablets for seasonal allergic rhinitis.

This paper compares cost-efficacy ratios for intranasal fluticasone propionate and terfenadine tablets within a sample of patients with seasonal allergic rhinitis symptoms due to mountain cedar allergy. Efficacy was assessed using secondary data analysis of patient ratings of symptoms and their overall assessment of response to treatment within a previously conducted clinical trial. Costs include direct costs of the drugs used for therapy. Patients with documented mountain cedar allergy who were 12 years of age or older (N = 232) had been randomized to either receive intranasal fluticasone propionate, terfenadine, or placebo. The cost-efficacy ratios for intranasal fluticasone propionate 200 micrograms once daily were more favorable than the ratios for terfenadine 60 mg twice daily. This relationship remained throughout the sensitivity analysis. Because intranasal fluticasone propionate is only available in a fixed package size, the number of efficacy-adjusted days of terfenadine therapy that could be purchased to reach break-even costs for a 30-day supply of fluticasone was calculated. Cost efficacy-adjusted days ranged from 11 to 18 days. If cost-efficacy adjustments are not conducted, the upper end of the range increases from 18 to 22 days, since 22 days of terfenadine could be purchased for the price of a 30-day supply of intranasal fluticasone propionate. Depending on which of the efficacy measures the reader believes, if patients use terfenadine for longer than 11 to 22 days, fluticasone propionate is the more cost-efficacious choice. Because most allergies are seasonal and allergy seasons typically last longer than 11 to 22 days, it is likely that fluticasone propionate will frequently be the more cost-efficacious choice in the patient population represented in this study.

A literature review comparing the economic, clinical, and humanistic attributes of dihydroergotamine and sumatriptan.

The value of different pharmaceuticals in treating migraine is frequently based on clinical efficacy only. This article assumes a broader perspective and compares the clinical, economic, and humanistic attributes of two antimigraine medications, dihydroergotamine (DHE) and sumatriptan, based on a literature review. DHE is an established product with over 40 years of use in the treatment of migraine. Sumatriptan is a new product with a higher acquisition cost than DHE. Because sumatriptan costs more than DHE, the question must be asked. "Does sumatriptan provide advantages that offset this price differential?" This question reflects the growing concern among payers and patients over the cost and effectiveness of therapies. However, it is not easily answered. Direct comparative data are not available, and data sources are different for the two products. Moreover, the products are currently marketed in different dosage forms--intramuscular for DHE and subcutaneous for sumatriptan. The literature reviewed indicates that the clinical attributes of the two products are similar, with each having slightly different advantages and disadvantages. However, the DHE literature is generally limited to uncontrolled studies, whereas the sumatriptan literature reports the results of rigorously designed, randomized, double-blind, placebo-controlled clinical trials. Published data on the products' economic and humanistic attributes are limited. We concluded that the literature does provide important, albeit limited, data on the economic, clinical, and humanistic attributes of DHE and sumatriptan that permit restricted comparisons. The limitations of the data highlight the need for comparative studies of these products' multidimensional attributes both in controlled clinical trials and under actual practice conditions.

Comparing dihydroergotamine mesylate and sumatriptan in the management of acute migraine. A retrospective cost-efficacy analysis.

The annual cost of managing migraine totals billions of US dollars. This retrospective economic analysis of a clinical trial comparing subcutaneous dihydroergotamine mesylate (DHE) with subcutaneous sumatriptan in the treatment of acute migraine is appropriate because, although each product has been shown to be efficacious, the acquisition cost of sumatriptan is over 3 times that of DHE. Total costs in each treatment group were calculated and applied independently to 11 clinical trial efficacy measures. Three of the efficacy measures showed no statistically significant difference between treatment arms, leading to a decision to use the less expensive DHE. In 4 of the efficacy measures. DHE was the obvious choice because it is more efficacious and less expensive. For the final 4 efficacy measures, where sumatriptan is more efficacious and more expensive, incremental cost-efficacy ratios were calculated to determine the additional expenditure required to achieve outcomes associated with quick relief. Depending on the efficacy variable chosen and the assumptions used in the model, the incremental cost-efficacy ratios ranged from $US4000 to $US6700 per year (1993 dollars) for each additional patient who is successfully treated with sumatriptan compared with DHE. Therefore, in a population of 100 migraineurs, an additional 13 to 22 patients would achieve these short term benefits of sumatriptan, although it would cost an additional $US88 395 annually, given the assumptions made. Because each product has unique advantages, we conclude that the more cost-efficacious product is dependent on the outcome of interest and the amount that the patient or provider is willing to pay to achieve that outcome.

Economic outcomes for the treatment of allergic rhinitis.

The purpose of this article is to review the literature related to economic outcomes associated with treating allergic rhinitis. A literature review was conducted using 'Medline' and the in-house database of the publishers of this journal for articles published between January 1991 and January 1996. Only 3 cost-outcome analyses that compared alternative treatments for allergic rhinitis were found. Given the limited number of full economic evaluations, much of this article focuses on issues related to direct and indirect costs and outcome measures that should be considered when performing an economic evaluation of allergic rhinitis. We conclude that more comprehensive analyses using a wide array of costs and outcomes are needed. At present, it is not possible to draw general conclusions regarding the economic value of alternative treatments for allergic rhinitis.

Multivariate analysis of health status scores: chronic airway disorders and the MOS SF-36.

Multivariate analysis of variance (MANOVA) with follow-up canonical discriminant analysis may be used to interpret differences in health-related quality of life measured by the Medical Outcome Study Short Form 36 (MOS SF-36). Due to the moderate correlations between the 8 health dimensions of the SF-36, MANOVA is theoretically a more appropriate method than traditional univariate approaches for detecting group differences on the SF-36. Additionally, canonical discriminant analysis presents a novel approach to understanding the relationship between health dimensions of the SF-36 and model-independent variables. Results from the MANOVA and canonical discriminant analysis provide evidence of the sensitivity of the SF-36 in cross-sectional, self-reported data. Significant differences in health status (alpha less than or equal to 0.05) were found for the variables of age, and primary physician visits, and between levels of disease severity, type of breathing problem, whether patients had seen a specialist or not, use of emergency room, the comorbid states of depression and arthritis, and income. No significant differences in health status were reported between males and females or racial groups.

Economic impact of cost-containment strategies in third party programmes in the US. Part II.

This is the second article in a 2-part series that examines the economic impact of several different strategies used to control costs in third party programmes. This article investigates 5 different methods: (a) formularies; (b) capitation; (c) drug utilisation review; (d) prior approval; and (e) drug product selection. The published literature indicates that use of formularies decreases drug expenditures, but these savings may be offset by expenditures in other areas of healthcare programmes. Capitation, though less well studied than other strategies, may show some effectiveness in reducing costs by increasing generic dispensing and promoting switching from prescription drug to over-the-counter. Drug utilisation review, as a systematic programme of claims data review, has been shown to yield positive economic return in a variety of areas, including both impersonal and face-to-face educational interventions with healthcare practitioners. Prior approval and drug product selection both result in savings when examined in isolation from other aspects of healthcare. Cost-shifting, administrative costs and costs incurred because of possible decreased access to care have yet to be fully accounted for.

Restacorin, a new antiarrhythmic drug: a review of its electrophysiologic and hemodynamic properties.

Restacorin is a recently developed effective antiarrhythmic agent with primarily class Ic properties. The present paper reviews the electrophysiologic and hemodynamic effects of this compound. The major electrophysiologic effects are a depression of Vmax and an increase in AH, HV and QRS duration. The administration of restacorin does not induce significant side effects. In subjects with a normal left ventricular function, restacorin does not show negative inotropic effects. However, in patients with a decreased left ventricular function, restocorin produces a moderate negative inotropic effect.