Phaeochromocytoma in multiple endocrine neoplasia type 2: RET codon-specific penetrance and changes in management during the last four decades.

OBJECTIVES: We describe phaeochromocytoma (phaeo) penetrance in multiple endocrine neoplasia type 2 (MEN2) according to RET protooncogene-specific mutations and report changes in phaeo diagnosis and management from 1968 to 2015. DESIGN: This retrospective chart review included 309 MEN2 patients from one specialized ambulatory care centre. Phaeo patients were categorized by diagnosis date: early, 1968-1996, n=40, and recent, 1997-2015, n=45. RESULTS: Phaeochromocytoma was diagnosed in 85/309 patients with RET mutations in the following exons (phaeos/all carriers, %): exon 11 (56/120, 46.6%); exon 16 (7/17, 41.2%), exon 10 (14/47, 29.8%), and exon 13-15 (2/116, 1.7%). Age at phaeo diagnosis differed according to affected exon: 21.9±1.5 years, exon 16; 34.1±11.6 years, exon 11; and 41.8±8.8 years, exon 10. Age-related phaeo penetrance differed among five amino acid substitutions at codon 634 and was highest for Cys634Arg and Cys634Tyr. Age at diagnosis was 34.4±11.6 years in the early and recent groups. Phaeochromocytoma and medullary thyroid carcinoma (MTC) were diagnosed synchronously in 21/40 (early) vs 8/45 (recent) and metachronously in 19/40 vs 37/45 cases. Diagnostic methods significantly changed from clinical (22/40 vs 4/45) to biochemical and/or imaging based (14/40 vs 35/45). Phaeochromocytoma diameter at diagnosis was 4.6 vs 2.6 cm. CONCLUSION: Phaeochromocytoma penetrance and age of diagnosis are highly correlated with MTC aggressiveness based on RET mutation status, with higher penetrance and younger age of diagnosis associated with more aggressive MTC. Penetrance steadily increases with age. At-risk patients require lifelong follow-up.

Assessment of potential measures in models of progression in Alzheimer disease.

BACKGROUND: In estimating the potential benefits of treatment, it is often necessary to extrapolate beyond clinical trial results using economic modeling. Previous attempts in Alzheimer disease (AD) were primarily based on the Mini-Mental State Examination (MMSE) due to its widespread use. These models were criticized as not accurately reflecting the total impact of the disease, providing untrustworthy estimates of treatment benefit. We compared 3 alternatives to the MMSE with respect to bridging between clinical outcomes needed for regulatory approval and economic and quality of life (QOL) outcomes important to reimbursement agencies. METHODS: The MMSE, Disability Assessment in Dementia (DAD) scale, Clinical Dementia Rating (CDR) scale, and Dependence Scale (DS) were compared in their ability to explain variation in cognitive, functional, and behavioral measures as well as economic and QOL outcomes using univariate (Pearson correlations) and multivariate (linear regression) analyses of data from research sites in the United States and Europe. RESULTS: Subjects with mild to moderate AD (n = 196; mean 75.9 years; 56% female) were evaluated. The DS, DAD, and CDR were moderately correlated with the MMSE (Pearson correlations, range 0.54-0.58) but performed better (higher adjusted R(2)) than the MMSE in explaining variations in subject behavior, QOL, and health status. The DS and DAD performed better in explaining variation in medical costs, caregiver QOL, and caregiver time. CONCLUSIONS: Measures of function (DAD) or dependence on others (DS), or global measures (CDR), appear to be better candidates than the MMSE for modeling AD progression.

Study of stretched polypropylene fibres by 1H pulsed and CW NMR spectroscopy.

A set of stretched isotactic polypropylene fibres prepared with the draw ratio lambda=4 at four different stretching temperatures was investigated by H1 pulsed relaxation NMR methods and CW NMR spectroscopy. We have studied the influence of the stretching temperature and draw ratio upon the changes of structure and molecular mobility. Some information on the influence of these conditions was obtained from CW NMR measurements by means of the temperature dependences of second moment M(2) and decomposition of NMR spectra into elementary components corresponding to the chains with different mobility. H1 CW NMR spectra were measured at two (14.1 and 10.5 MHz) Larmor frequencies in the temperature range 200-420 K. An analysis of the experimental data shows that the stretching of the fibres at different temperature results in a change of molecular mobility. Spin-lattice relaxation times in laboratory (T(1)) and rotating (T(1rho)) frames were also measured on the set of the fibres in the temperature range 239-423 K at 30 MHz Larmor frequency employing a home made pulse spectrometer. In the rotating frame spin-lattice relaxation time measurements in the temperature range above 278 K three relaxation times T(1rho) have been observed. The minima of the temperature dependences of the observed relaxation times reflect an alpha-relaxation process in crystalline regions and beta-relaxation process related to a double glass transition in the non-crystalline regions of the studied fibres.

Impact of compliance and persistence with bisphosphonate therapy on health care costs and utilization.

UNLABELLED: The impact of persistence and compliance with bisphosphonate therapy on health care costs and utilization was examined in women newly prescribed bisphosphonates. At 3 years, women who were persistent and compliant with bisphosphonate therapy had lower total costs compared with non-persistent and non-compliant women, after controlling for relevant risk factors. INTRODUCTION: The impact of persistence and compliance with bisphosphonate therapy on health care costs and utilization was examined in bisphosphonate-naïve women. METHODS: Two claims databases were used to identify women > or = 45 years of age and who filled a new bisphosphonate prescription during 2000-2002. Persistence and compliance were evaluated over 3 years. Compliance was defined as a medication possession ratio (days of bisphosphonate supply/days of follow-up) > or = 0.80; persistence was defined as no refill gaps > or = 30 days. Multivariate models accounted for potential confounders. RESULTS: This analysis included 32,944 women (mean age, 64 years) who filled a new prescription for daily or weekly alendronate (n = 26,581) or risedronate (n = 6,363). At 3 years, 37% of women were compliant and 21% of women were persistent. Unadjusted total mean health care costs were lower for the compliant vs. non-compliant and persistent vs. non-persistent cohorts. After adjusting for potential confounders, total health care costs were reduced by 8.9% for persistent patients (p < 0.001) and 3.5% for compliant patients (p = 0.014). Persistence decreased the likelihood of inpatient admission by 47%. CONCLUSION: At 3 years, women who were persistent and compliant with bisphosphonate therapy had lower total costs compared with non-persistent and non-compliant women, after controlling for relevant risk factors.

National estimates of the quantity and cost of informal caregiving for the elderly with dementia.

OBJECTIVE: Caring for the elderly with dementia imposes a substantial burden on family members and likely accounts for more than half of the total cost of dementia for those living in the community. However, most past estimates of this cost were derived from small, nonrepresentative samples. We sought to obtain nationally representative estimates of the time and associated cost of informal caregiving for the elderly with mild, moderate, and severe dementia. DESIGN: Multivariable regression models using data from the 1993 Asset and Health Dynamics Study, a nationally representative survey of people age 70 years or older (N = 7,443). SETTING: National population-based sample of the community-dwelling elderly. MAIN OUTCOME MEASURES: Incremental weekly hours of informal caregiving and incremental cost of caregiver time for those with mild dementia, moderate dementia, and severe dementia, as compared to elderly individuals with normal cognition. Dementia severity was defined using the Telephone Interview for Cognitive Status. RESULTS: After adjusting for sociodemographics, comorbidities, and potential caregiving network, those with normal cognition received an average of 4.6 hours per week of informal care. Those with mild dementia received an additional 8.5 hours per week of informal care compared to those with normal cognition (P < .001), while those with moderate and severe dementia received an additional 17.4 and 41.5 hours (P < .001), respectively. The associated additional yearly cost of informal care per case was 3,630 dollars for mild dementia, 7,420 dollars for moderate dementia, and 17,700 dollars for severe dementia. This represents a national annual cost of more than 18 billion dollars. CONCLUSION: The quantity and associated economic cost of informal caregiving for the elderly with dementia are substantial and increase sharply as cognitive impairment worsens. Physicians caring for elderly individuals with dementia should be mindful of the importance of informal care for the well-being of their patients, as well as the potential for significant burden on those (often elderly) individuals providing the care.

Effect of nonsteroidal anti-inflammatory drug use on the rate of gastrointestinal hospitalizations among people living in long-term care.

OBJECTIVES: Gastrointestinal (GI) complications are the most-common serious adverse reactions associated with nonsteroidal anti-inflammatory drugs (NSAIDs). We quantified the effect of specific NSAIDs on the rate of GI hospitalizations among older people living in long-term care. DESIGN: Retrospective cohort study. SETTING: All Medicare/Medicaid certified nursing homes in four states (Maine, Minnesota, New York, and South Dakota). PARTICIPANTS: We identified 125,516 newly admitted residents from a database of all residents (1992-1996) of all Medicare/Medicaid certified nursing homes in four states. Using the federally mandated Minimum Data Set, which includes information on all drugs received (prescription and over-the-counter), we identified patients who received at least one prescription for aspirin (n = 19,101) or NSAIDs (n = 9,777). The control population consisted of all institutionalized persons who did not receive these drugs. MEASUREMENTS: From Health Care Financing Administration inpatient claims, we identified the first hospitalization for GI perforation, ulcer, or hemorrhage that occurred during the year of follow up (ICD9-CM discharge codes: 531-534, 578). Cox proportional hazards models provided adjusted estimates of rate ratios. RESULTS: NSAID exposure increased the GI-event-related hospitalization rate in both men (rate ratios (RR) = 2.64; 95% confidence interval (CI) = 1.17-5.99) and women (RR = 3.23; 95% CI = 1.85-5.65). The rate of GI hospitalizations for both men and women taking sulindac, naproxen, or indomethacin was higher than for nonusers. The risk of GI-event-related hospitalizations was greatest among women exposed to diflunisal (RR = 6.08; 95% CI = 2.27-16.26) or oxaprozin (RR = 6.03; 95% CI = 2.49-14.58). CONCLUSIONS: Despite the high background rate of GI events, most NSAIDs increased the risk of GI hospitalization. Careful attention to choice of agent and dosing is needed in prescribing NSAIDs in this frail, older population.

Efficient patient identification strategies for women with osteoporosis.

The purpose of this analysis was to identify efficient (highest sensitivity at each level of cost) strategies to detect osteoporosis in postmenopausal women. Our study sample consisted of 392 women (age >/=50 yr) who were retirees or active employees of a corporation. The Simple Calculated Osteoporosis Risk Estimation (SCORE) questionnaire was completed, and bone mineral density levels were collected at the forearm using peripheral dual X-ray absorptiometry (pDXA), and at the femoral neck and lumbar spine using central DXA. Osteoporotic women were those with a T-score of -2.5 or less at any one of the three skeletal sites tested. Assumed costs were $5 for SCORE, $35 for pDXA, $120 for DXA at either the hip or spine, and $200 for DXA at both the hip and spine. The analysis indicated that the current "gold standard" is inefficient relative to other strategies investigated. By comparison, a tiered strategy consisting of SCORE, pDXA, and then selective use of DXA at both the hip and spine identified 90% of the women with osteoporosis at a cost of only $106 per woman tested. In choosing among the efficient strategies, decision makers must determine the extent to which they are willing to trade off higher program cost for greater sensitivity.

Employment trends and the traditional baccalaureate health administration student.

Baccalaureate programs in health administration serve both traditional undergraduates--usually age 18 to 22 with little experience--and older adult students with more experience. The former group of students, as well as some older students who are changing their fields, are sometimes not as well informed as graduate students and adult undergraduates with health care experience about the impact of changes in the health care sector on employment opportunities. Furthermore, career advisers in placement offices may not be able to keep pace with the rapid change in health care. This article examines past and future changes in employment opportunities for baccalaureate students, with a particular focus on the changes that are occurring in sector employment growth. The implications of the continued shrinking in the acute care sector, the growth of managed care, the increased complexity of physician group management, and the ongoing rise in long-term care for employment are too often missed by students with limited experience in health care.

[The effect of Zindep inj. preparation on levels of zinc, T-lymphocytes and beta-lysine in the blood of pregnant dairy cows]. / Vplyv prípravku Zindep inj. na zinkémiu, T-lymfocyty a beta-lyzín u gravidných dojníc.

The effects of zinc administration at a rate of 3 mg/kg lw. in the preparation Zindep inj. ad usum vet. (Biotika, Slovenská L'upca) were evaluated as exerted on zinc concentrations in the blood serum of 16 dairy cows in the middle of the 7th month of pregnancy. With respect to zinc injection, T-rosetted lymphocytes and beta-lysine activity were inestigated. Blood was collected from all dairy cows from v. jugularis before the preparation was administered, on days 2, 5, 8, 15, 30 and 60 after Zindep administration. Atom absorption spectrophotometry, applying a flame technique on a Perkin Elmer 1100 apparatus (Bíres, 1986), was used to determine Zn concentrations in the blood serum of all dairy cows. T-lymphocytes were determined by a rosette test after Paul et al. (1977), and beta-lysine was detected spectrophotometrically after Bucharin et al. (1987). Zinc dynamics in the blood serum of dairy cows is presented in Fig. 1. The starting values of zinc in the test cows were 9.68 +/- 2.30 mumol/l and in the control ones 10.15 +/- 1.27 mumol/l. Zincaemia of experimental dairy cows was significantly lower (P less than 0.01) on day 2 after Zindep administration, in comparison with the control group. A significant increase in zinc concentrations in the blood serum of experimental animals, in comparison with the control ones, was observed from day 8 to day 60 (P less than 0.01). The maximum zincaemia values were recorded in experimental dairy cows within days 15 and 30 (15.65 +/- 3.33, and/or 14.55 +/- 2.10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)