Second fractures among older adults in the year following hip, shoulder, or wrist fracture.

UNLABELLED: We report on second fracture occurrence in the year following a hip, shoulder or wrist fracture using insurance claims. Among 273,330 people, 4.3 % had a second fracture; risk did not differ by first fracture type. Estimated adjusted second fracture probabilities may facilitate population-based evaluation of secondary fracture prevention strategies. INTRODUCTION: The purpose of this study was estimate second fracture risk for the older US population in the year following a hip, shoulder, or wrist fracture. METHODS: Observational cohort study of Medicare fee-for-service beneficiaries with an index hip, shoulder, or wrist fragility fracture in 2009. Time-to-event analyses using Cox proportional hazards models to characterize the relationship between index fracture type (hip, shoulder, wrist) and patient factors (age, gender, and comorbidity) on second fracture risk in the year following the index fracture. RESULTS: Among 273,330 individuals with fracture, 11,885 (4.3 %) sustained a second hip, shoulder or wrist fracture within one year. Hip fracture was most common, regardless of the index fracture type. Comparing adjusted second fracture risks across index fracture types reveals that the magnitude of second fracture risk within each age-comorbidity group is similar regardless of the index fracture. Men and women face similar risks with frequently overlapping confidence intervals, except among women aged 85 years or older who are at greater risk. CONCLUSIONS: Regardless of index fracture type, second fractures are common in the year following hip, shoulder or wrist fracture. Secondary fracture prevention strategies that take a population perspective should be informed by these estimates which take competing mortality risks into account.

Predicting EQ-5D-US and SF-6D societal health state values from the Osteoporosis Assessment Questionnaire.

SUMMARY: Linear regression was applied to data from 275 persons with osteoporosis-related fracture to estimate EQ-5D-US and SF-6D health state values from the Osteoporosis Assessment Questionnaire. The models explained 56% and 58% of the variance in scores, respectively, and root mean square error values (0.096 and 0.085) indicated adequate prediction for use when actual values are unavailable. INTRODUCTION: This study was conducted to provide models that predict EQ-5D-US and SF-6D societal health state values from the Osteoporosis Assessment Questionnaire (OPAQ). METHODS: OPAQ, EQ-5D, and SF-6D data from individuals at two centers with prior osteoporosis-related fracture were used. Fractures were classified by type as hip/hip-like, spine/spine-like, or wrist/wrist-like. Spearman rank correlations between preference-based system (EQ-5D and SF-6D) dimensions and OPAQ subscales were estimated. Linear regression was used to estimate preference-based system health state values based on OPAQ subscales. We assessed models including age, sex, and fracture type and chose the model with the best performance based on the root mean square error (RMSE) estimate. RESULTS: Among the 275 participants (198 women), with mean age of 68 years (range 50-94), the distribution of fracture types included 10% hip/5% hip-like, 18% spine/11% spine-like, and 24% wrist/18% wrist-like. The final regression model for EQ-5D-US included three OPAQ attributes (physical function, emotional status, and symptoms), predicted 56% of the variance in EQ-5D-US scores, and had a RMSE of 0.096. The final model for SF-6D, which included all four OPAQ dimensions, predicted 58% of the variance in SF-6D scores and had a RMSE of 0.085. CONCLUSIONS: Two models were developed to estimate EQ-5D-US and SF-6D health state values from OPAQ and demonstrated adequate prediction for use when actual values are not available.

Neuroleptic malignant syndrome: a diagnosis easily missed.

A woman admitted with psychotic depression developed a number of physical problems. Urinary incontinence, headache, neck stiffness and breathing difficulties were all treated separately but were later found to be part of the neuroleptic malignant syndrome. Treatment of the disorder led to complete recovery. We review the criteria for diagnosis of this serious disorder and some differential diagnoses.

Gender differences in the results of the final medical examination at University College Dublin.

OBJECTIVES: In 1984 females made up 45% of medical undergraduates in Ireland. By 1996 this proportion had increased to 57%. This study examines gender differences in performance at final medical examinations, with a view to ascertaining the impact of the change in proportion of females attending medical school. DESIGN: Final year examination results of medical students over a 5-year period (1992-96) were obtained from the broadsheets of University College Dublin (UCD) examinations office. The results of 557 students (females n=277; males=280) were analysed for all final year examinations (n=5). SETTING: University College Dublin. SUBJECTS: Final year medical students. RESULTS: Overall females were found to have performed better than their male counterparts. They were more likely to achieve an honours grade and had a similar or lower likelihood of passing or failing. Gender differences in performance were most marked in paediatrics (P < 0.01), psychiatry (P < 0.01) and obstetrics and gynaecology (P=0.01), females being more successful in each case. CONCLUSIONS: The success of females and their increased numbers at undergraduate level are not reflected at senior registrar and consultant level. As medical manpower becomes more of an issue the lack of women, particularly in certain specialties, and the possible reasons for this need to be addressed.

Efficacious, orally bioavailable thrombin inhibitors based on 3-aminopyridinone or 3-aminopyrazinone acetamide peptidomimetic templates.

We have addressed the key deficiency of noncovalent pyridinone acetamide thrombin inhibitor L-374,087 (1), namely, its modest half-lives in animals, by making a chemically stable 3-alkylaminopyrazinone bioisostere for its 3-sulfonylaminopyridinone core. Compound 3 (L-375,378), the closest aminopyrazinone analogue of 1, has comparable selectivity and slightly decreased efficacy but significantly improved pharmacokinetics in rats, dogs, and monkeys to 1. We have developed an efficient and versatile synthesis of 3, and this compound has been chosen for further preclinical and clinical development.

L-374,087, an efficacious, orally bioavailable, pyridinone acetamide thrombin inhibitor.

Replacement of the amidinopiperidine P1 group of 3-benzylsulfonylamino-6-methyl-2-pyridinone acetamide thrombin inhibitor L-373,890 (2) with a mildly basic 5-linked 2-amino-6-methylpyridine results in an equipotent compound L-374,087 (5, Ki = 0.5 nM). Compound 5 is highly selective for thrombin over trypsin, is efficacious in the rat ferric chloride model of arterial thrombosis and is orally bioavailable in dogs and cynomolgus monkeys. The structural basis for the critical importance of both methyl groups in 5 was confirmed by X-ray crystallography.

Genetic maternity and paternity in a local population of armadillos assessed by microsatellite DNA markers and field data.

Genetic data from polymorphic microsatellite loci were employed to estimate paternity and maternity in a local population of nine-banded armadillos (Dasypus novemcinctus) in northern Florida. The parentage assessments took advantage of maximum likelihood procedures developed expressly for situations when individuals of neither gender can be excluded a priori as candidate parents. The molecular data for 290 individuals, interpreted alone and in conjunction with detailed biological and spatial information for the population, demonstrate high exclusion probabilities and reasonably strong likelihoods of genetic parentage assignment in many cases; low mean probabilities of successful reproductive contribution to the local population by individual armadillo adults in a given year; and statistically significant microspatial associations of parents and their offspring. Results suggest that molecular assays of highly polymorphic genetic systems can add considerable power to assessments of biological parentage in natural populations even when neither parent is otherwise known.

Molecular documentation of polyembryony and the micro-spatial dispersion of clonal sibships in the nine-banded armadillo, Dasypus novemcinctus.

A battery of allelic markers at highly polymorphic microsatellite loci was developed and employed to confirm genetically, the clonal nature of sibships in nine-banded armadillos. This phenomenon of consistent polyembryony, otherwise nearly unknown among the vertebrates, was capitalized upon to describe the micro-spatial distributions of numerous clonal sibships in a natural population of armadillos. Adult clone mates were significantly more dispersed than were juvenile sibs, suggesting limited opportunities for altruistic behavioural interactions among mature individuals. These results, and considerations of armadillo natural history, suggest that evolutionary explanations for polyembryony in this species may not reside in the kinds of ecological and kin selection theories relevant to some of the polyembryonic invertebrates. Rather, polyembryony in armadillos may be associated evolutionarily with other reproductive peculiarities of the species, including delayed uterine implantation of a single egg.

Seasonal and spatial trends in the detectability of leprosy in wild armadillos.

A survey for leprosy among 565 armadillos from Louisiana and Texas found IgM antibodies to the phenolic glycolipid-1 antigen of Mycobacterium leprae in 16% of the animals. There were no geographic trends in the distribution of prevalence rates between the sites and the disease probably has a much greater range. Repeat observations in one location showed significant seasonal variations in the observable antibody prevalence rate, but the yearly average remained similar. Infected armadillos tended to be heavier, and the females usually had plasma progesterone concentrations indicative of sexual maturity. Using these characteristics to stratify the populations into adult and sub-adult cohorts, variations in the observable leprosy prevalence rate were seen to be proportional to changes in the age structure of the populations. Leprosy appears to be maintained in steady state within some regions, and nearly a third of the adult armadillos in Louisiana and Texas harbour M. leprae.

Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation.

The influence of total-body irradiation (TBI) and autologous or allogeneic bone marrow transplantation on serum immunoglobulin subclasses was determined in a dog model. Only IgG1 levels decreased after low-dose (+/- 4.5 Gy) TBI, but levels of all immunoglobulin classes fell after high-dose TBI (8.5 GyX1 or 2X6.0 Gy). After autologous bone marrow transplantation IgM levels were the first and IgE levels were the last to return to normal. After successful allogeneic bone marrow transplantation prolonged low IgM and IgE levels were found but IgA levels increased rapidly to over 150% of pretreatment values. A comparison of dogs with or without clinical signs or graft-versus-host disease (GVHD), revealed no differences in IgM levels. Dogs with GVHD had higher IgA but lower IgE levels. Dogs that rejected their allogeneic bone marrow cells showed significant early rises in IgE and IgA levels in comparison with dogs with GVHD. These results differ from the observations made on Ig levels in human bone marrow transplant patients. No significant differences in phytohemagglutinin stimulation tests were found between dogs with or without GVHD or dogs receiving an autologous transplant for the first four months after TBI and transplantation. An early primary or secondary involvement of humoral immunity in GVHD and graft rejection in dogs is postulated.