RESUMEN

With an increased interest in the use of molten salts in both nuclear and non-nuclear systems, measuring important thermophysical properties of specific salt mixtures becomes critical in understanding salt performance and behavior. One of the more basic and significant thermophysical properties of a given salt system is density as a function of temperature. With this in mind, this work aims to present and layout a novel approach to measuring densities of molten salt systems using neutron radiography. This work was performed on Flight Path 5 at the Los Alamos Neutron Science Center at Los Alamos National Laboratory. In order to benchmark this initial work, three salt mixtures were measured, NaCl, LiCl (58.2 mol%) + KCl (41.8 mol%), and MgCl2 (32 mol%) + KCl (68 mol%). Resulting densities as a function of temperature for each sample from this work were then compared to previous works employing traditional techniques. Results from this work match well with previous literature values for all salt mixtures measured, establishing that neutron radiography is a viable technique to measure density as a function of temperature in molten salt systems. Finally, advantages of using neutron radiography over other methods are discussed and future work in improving this technique is covered.

RESUMEN

The authors have created a radiation transport code using the GEANT4 Monte Carlo toolkit to simulate pediatric patients undergoing CT examinations. The focus of this paper is to validate their simulation with real-world physical dosimetry measurements using two independent techniques. Exposure measurements were made with a standard 100-mm CT pencil ionization chamber, and absorbed doses were also measured using optically stimulated luminescent (OSL) dosimeters. Measurements were made in air with a standard 16-cm acrylic head phantom and with a standard 32-cm acrylic body phantom. Physical dose measurements determined from the ionization chamber in air for 100 and 120 kVp beam energies were used to derive photon-fluence calibration factors. Both ion chamber and OSL measurement results provide useful comparisons in the validation of the Monte Carlo simulations. It was found that simulated and measured CTDI values were within an overall average of 6% of each other.

Asunto(s)

RESUMEN

The goal was to develop and implement a comprehensive, primarily face-to-face handoff process that begins in the operating room and concludes at the bedside in the intensive care unit (ICU) for pediatric patients undergoing congenital heart surgery. Involving all stakeholders in the planning phase, the framework of the handoff system encompassed a combination of a formalized handoff tool, focused process steps that occurred prior to patient arrival in the ICU, and an emphasis on face-to-face communication at the conclusion of the handoff. The final process was evaluated by the use of observer checklists to examine quality metrics and timing for all patients admitted to the ICU following cardiac surgery. The process was found to improve how various providers view the efficiency of handoff, the ease of asking questions at each step, and the overall capability to improve patient care regardless of overall surgical complexity.

Asunto(s)

RESUMEN

Eastern North Carolina is a major contributor to both turkey and swine production in the United States. In this region, turkeys and swine are frequently grown in close proximity and by common growers. To further characterize colonization of turkeys and swine with Campylobacter in such a setting, we investigated the prevalence of thermophilic campylobacters in eight paired operations involving turkey farms in close proximity to finishing swine farms. All 15 surveyed flocks and 15 herds were Campylobacter positive at one or more sampling times. Campylobacter was isolated from 1,310 (87%) of the 1,512 turkey samples and 1,116 (77%) of the 1,448 swine samples. Most (> 99%) campylobacters from swine samples were Campylobacter coli, found in 59 to 97% of the samples from the different herds. Both Campylobacterjejuni and C. coli were recovered from the turkey flocks (overall prevalences of 52 and 35%, respectively). Prevalence among flocks ranged from 31 to 86% for C. jejuni and 0 to 67% for C. coli, and both species were recovered from most flocks. Relative prevalence of C. coli was higher in young birds (brooders), whereas C. jejuni predominated in grow-out birds (P < 0.0001). The prevalence of C. coli in a swine herd was generally not a good predictor for prevalence of this species in the corresponding turkey flock. These findings indicate that even though turkeys and swine grown in proximity to each other were commonly colonized with thermophilic campylobacters, the relative prevalences of C. jejuni and C. coli appear to be host associated.

Asunto(s)

RESUMEN

S-nitrosoglutathione (GSNO) stabilizes the alpha-subunit of hypoxia inducible factor-1 (HIF-1) in normoxic cells, but not in the presence of PI3K inhibitors. In this report, the biochemical pathway by which GSNO alters PI3K/Akt activity to modify HIF-1 expression was characterized in Cos cells and primary pulmonary vascular endothelial cells. GSNO increased Akt kinase activity--and downstream HIF-1alpha protein accumulation and DNA-binding activity--in a dose- and time-dependent manner. The PI3K inhibitors, wortmannin and LY294002, blocked these responses. Neither glutathione nor 8-bromo-cyclic GMP mimicked the GSNO-induced increases in Akt kinase activity. GSNO-induced Akt kinase activity and downstream HIF-1alpha stabilization were blocked by acivicin, an inhibitor of gamma-glutamyl transpeptidase (gammaGT), a transmembrane protein that can translate extracellular GSNO to intracellular S-nitrosocysteinylglycine. Dithiothreitol blocked GSNO-induced Akt kinase activity and HIF-1alpha stabilization. Moreover, the 3'-phosphatase of phosphoinositides, PTEN (phosphatase and tensin homolog deleted on chromosome ten) was S-nitrosylated by GSNO in pulmonary arterial endothelial cells, which was reversed by dithiothreitol and ultraviolet light. Interestingly, the abundance of S-nitrosylated PTEN also correlated inversely with PTEN activity. Taken together, these results suggest that GSNO induction of Akt appears to be mediated by S-nitrosylation chemistry rather than classic NO signaling through guanylate cyclase/cGMP. We speculate that gammaGT-dependent activation of Akt and subsequent activation of HIF-1 in vascular beds may be relevant to the regulation of HIF-1-dependent gene expression in conditions associated with oxyhemoglobin deoxygenation, as opposed to profoundly low Po(2), in the pulmonary vasculature.

Asunto(s)

RESUMEN

Commercial turkey flocks in North Carolina have been found to be colonized frequently with Campylobacter coli strains that are resistant to several antimicrobials (tetracycline, streptomycin, erythromycin, kanamycin, and ciprofloxacin/nalidixic acid). Such strains have been designated multidrug resistant (MDR). However, the population structure of MDR C. coli from turkeys remains poorly characterized. In this study, an analysis of multilocus sequence typing (MLST)-based sequence types (STs) of 59 MDR strains from turkeys revealed that the majority of these strains corresponded to one of 14 different STs, with three STs accounting for 41 (69%) of the strains. The major STs were turkey specific, and most (87%) of the strains with these STs were resistant to the entire panel of antibiotics mentioned above. Some (13%) of the strains with these STs were susceptible to just one or two of the antibiotics in this panel. Further subtyping using fla typing and pulsed-field gel electrophoresis with SmaI and KpnI revealed that the major MDR STs corresponded to strains of related but distinct subtypes, providing evidence for genomic diversification within these STs. These findings suggest that MDR strains of C. coli from turkeys have a clonal population structure characterized by the presence of a relatively small number of clonal groups that appear to be disseminated in the turkey production system. In addition, the observed correlation between STs and the MDR profiles of the microbes indicates that MLST-based typing holds potential for source-tracking applications specific to the animal source (turkeys) and the antimicrobial resistance profile (MDR status) of C. coli.

Asunto(s)

RESUMEN

As part of a study on ovarian and oviductal adenocarcinomas in older laying hens, 676 commercial egg-laying chickens were necropsied at 4 yr of age. Tumors were identified in 305 (45.1%) of the hens. Grossly visible metastatic tumors in the lungs of a few birds prompted collection of lungs from 228 affected hens for histologic examination. Metastatic adenocarcinomas were identified histologically in the lungs of 42 of the 228 hens (18.4%). The number of tumors and extent of involvement of the lung parenchyma varied from minimal to extensive. Tumor emboli were occasionally seen in pulmonary vessels. Metastatic foci showing expansive or invasive growth were identified. These findings indicate that vascular spread of adenocarcinomas is more common than previously thought in chickens, and the lungs are often involved with metastatic tumors, primarily from the reproductive tract.

Asunto(s)

RESUMEN

Previous studies have demonstrated a detrimental effect of seminal plasma on the maintenance of motility of cooled equine spermatozoa; however, the mechanism for the adverse effect of seminal plasma during cooled storage remains undetermined. In goats, a glycoprotein component of bulbourethral gland secretion contains lipase activity that is detrimental to sperm motility when stored in skim milk-based extenders. The objective of the current study was to determine the amount of lipase activity in stallion seminal plasma and to determine the effect of added lipase on spermatozoal motility during cooled semen storage. In the first experiment, seminal plasma (1.0 ml) was assayed for lipase activity based upon hydrolysis of triglycerides (olive oil substrate) into free fatty acids and subsequent titration of pH change (SigmaDiagnostic Lipase Kit). Lipase activity in stallion seminal plasma was 0.36 +/- 0.02 Sigma units/ml, (mean + S.E.M.; n = 16 ejaculates from six stallions). In the second experiment, equine semen (three ejaculates from each of four stallions) was divided into five treatment aliquots. In Treatment 1, semen was extended 1:3 with nonfat dried skim milk extender (NFDSM). In treatment groups 2 through 5, spermatozoa were washed by centrifugation (300 x g for 15 min) and resuspended in NFDSM to a final concentration of 25 x 10(6) spermatozoa/ml. Porcine pancreatic lipase (pPL) was added to Treatment 3 (10 pPL units/ml), Treatment 4 (100 pPL units/ml) and Treatment 5 (100 pPL units/ml, heat inactivated at 100 degrees C for 5 min) while Treatment 2 had no pancreatic lipase added and served as the control. Samples were cooled slowly to 5 degrees C, and stored at 5 degrees C until evaluation. Sperm motility was evaluated at time 0, 24, 48 and 72 h by computerized semen analysis, and data were analyzed via repeated measures ANOVA. The addition of 100 units/ml but not 10 units/ml of pPL decreased (P < 0.01) total and progressive motility of stored sperm. Heat-inactivated pPL (Treatment 5) did not significantly decrease motility of spermatozoa during storage. Because the lipase activity assayed (Sigma units) and the lipase activity added to cooled semen (pPL units) were not equivalent, pPL was assayed in the Sigma Diagnostic Lipase assay. The relationship between Sigma Units (Y) and pPL units (X) appeared to be a log-linear relationship with log(Y) = -0.912 + 0.007X; R2 = 0.90. Mean lipase activity assayed in stallion seminal plasma was equivalent to approximately 64 pPL units/ml. These data suggest that endogenous lipase activity in stallion seminal plasma may be a factor in the adverse effects of seminal plasma on cooled spermatozoa in some stallions.

Asunto(s)

RESUMEN

A prospective ecologic study, using routinely collected data from commercial turkey companies, was done of 312 turkey flocks placed over a 1-yr period. The objective was to identify hatchery- and transportation-associated risk factors for poult mortality in the first 14 d after placement using statistical models. Logistic regression was used to determine the effects of hatchery-and transportation-related factors on odds of mortality for hen and tom flocks separately. Hatchery and transportation-related risk factors for hen flock mortality included truck, truck temperature, and number of poults dead on arrival at the farm. Hatchery and transportation-related risk factors for tom flock mortality included desnooding, truck, truck temperature, shipping time, and weather conditions at placement.

Asunto(s)

RESUMEN

A novel product (SQ12) for subcutaneous (SQ) injectable delivery of oxytetracycline (OTC) has been developed for use in livestock. SQ12 employs microfluidic spheres encasing OTC crystals, which allows for longer release of the OTC compared with other injectable antibiotics. The objectives of the study were to determine serum and tissue levels of SQ12 in turkey breeder hens to 14 days postinjection and to evaluate effects of SQ12 on reproductive status. Thirty photostimulated hens were housed in litter floor pens and provided with 14.5 hr of light per day in a curtain-sided facility. Six hens served as untreated controls. Twelve hens per treatment group received SQ injections in the neck with SQ12 at 11.4 (L dose group) or 22.7 mg/kg (H dose group) to assess low and high doses, respectively. Serum samples were obtained from each hen at predose and 6, 12, 24, 48, 72, 96, 168, 240, and 336 hr postinjection. All hens were euthanatized at 14 and 15 days postinjection. One-half of the hens in each treatment group were sampled (liver, lung, kidneys, and breast muscle) for tissue residue levels of OTC. The control group had no detectable OTC in serum or tissues at any sample collection time. There were no detectable serum levels of OTC in either treatment group prior to injection. The average serum concentrations of the L and H dose groups showed similar depletion curves although the H dose group was 42% higher at maximum concentration than the L group. Average tissue concentration of OTC for all tissues sampled from the H dose group was twice that of the L dose group. All tissue levels were below the OTC residue tolerance limit. SQ12 provided an extended source of OTC in serum of turkey breeder hens with no effect on reproductive status. SQ12 may provide for a novel treatment of bacterial infection in turkey breeder hens with longer lasting serum levels compared with other single injectable OTC products.

Asunto(s)

RESUMEN

Poult enteritis mortality syndrome (PEMS) is an economically devastating disease. To date, many questions about the syndrome remain unanswered, including its cause, transmission of causative agent(s), and control methods. Turkey coronavirus (TCV) infection has been associated with some outbreaks of PEMS, with areas having a higher prevalence of TCV infection also experiencing an increased incidence of PEMS. This study was designed to establish mortality patterns for flocks experiencing excess mortality and TCV infection in PEMS-affected regions and to delineate the possible role of TCV in PEMS-affected flocks. Fifty-four commercial turkey flocks on farms in areas with and without a history of TCV infection were monitored for weekly mortality and for antibodies to TCV. Flocks were chosen on the basis of placement dates and were monitored from day of placement until processing. All flocks were tested for TCV by an indirect fluorescent antibody assay. PEMS status was determined with the use of the clinical definition of mortality greater than 2% during any 3-wk period from 2 wk of age through the end of brooding due to unknown cause. Of the 54 flocks, 24 remained healthy, 23 experienced PEMS, and 7 tested positive for TCV but did not experience PEMS. Ten flocks experienced PEMS and tested positive for TCV, whereas 13 flocks experienced PEMS and did not test positive for TCV. Four health status groups were evident: healthy, PEMS positive, TCV positive, and PEMS + TCV positive. Distinct mortality patterns were seen for each of the four health status groups. Whereas TCV was associated with PEMS in 43% of PEMS cases, 13 cases (57%) of PEMS did not involve TCV. Additionally, 7 out of 17 cases of TCV (41%) did not experience excess mortality (PEMS) at any time during brooding of the flock. The results of this study indicate that TCV can be associated with PEMS but is neither necessary nor sufficient to cause PEMS.

Asunto(s)

RESUMEN

OBJECTIVE: To test Comprehensive Geriatric Assessment (CGA) as an adjunct to usual care. DESIGN: A randomized controlled trial with 3, 6, and 12 months follow-up. SETTING: Rural communities. PATIENTS: A total of 182 of 265 frail older patients (52 refused, 2 withdrawn, 27 ineligible, 2 deaths) referred by family practitioners with allocation to intervention (n = 95) or usual care (n = 87). INTERVENTION: Three-month implementation of CGA recommendations by a Mobile Geriatric Assessment Team (MGAT) with follow-up assessments at 3, 6, and 12 months. Geriatric nurse assessors, blinded to group assignment, performed each assessment. MAIN OUTCOME MEASURE: Goal Attainment Scaling (GAS). RESULTS: Baseline characteristics were comparable between groups. At 3 months, the intervention group was more likely to attain their goals (GAS total: chi = 46.4 +/- 5.9; GAS outcome chi = 48.0 +/- 6.6) compared with controls (total: chi = 38.7 +/- 4.1; outcome chi = 40.8 +/- 5.6) (P < .001). Standard assessments of function (Barthel index, instrumental activities of daily living), cognition (Mini-Mental State Examination), and quality of life (modified Spitzer quality of life index) showed no difference over 12 months. No difference in survival (intervention: chi = 320 days, SE = 6; control: chi = 294 days, SE = 6; P = .257) or time to institutionalization (intervention: 340 days, SE = 9; control: 342 days, SE = 8; log rank = 0.661; P = .416) were observed. CONCLUSIONS: A MGAT can target rural dwelling, frail older persons, perform in-home CGA, and develop an intervention strategy. Although the intervention did not prolong life or delay institutionalization, clinically important benefits were observed.

Asunto(s)

RESUMEN

Activation of the serine/threonine kinase Akt and the regulation of its activation are recognized as critical in controlling proliferative/survival signals via many hematopoietic receptors. In B lymphocytes, the B-cell receptor (BCR)-mediated activation of Akt is attenuated by co-cross-linking of BCR with the inhibitory receptor Fc gamma RIIB1, and the binding of the SH2 domain-containing inositol phosphatase, SHIP, to Fc gamma RIIB1. Because SHIP dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PIP3) and activation of Akt requires PIP3, the destruction of this phospholipid has been proposed as the mechanism for Akt inhibition. However, upstream kinases that activate Akt, such as PDK1, also require PIP3 for activation. In this report, we addressed whether SHIP inhibits Akt directly at the level of Akt recruitment to the membrane, indirectly through PDK recruitment/phosphorylation of Akt, or both. We generated stable B-cell lines expressing a regulatable, but constitutively membrane-bound Akt that still required PDK-dependent phosphorylation for activation. Several lines of evidence suggested that activation of this membrane-targeted Akt is not inhibited by Fc gamma RIIB1/SHIP and that PDK is not a target for SHIP-mediated inhibition. These data demonstrate that SHIP inhibits Akt primarily through regulation of Akt membrane localization. We also observed during these studies that Fc gamma RIIB1/SHIP does not inhibit p70(S6k) activation, even though several other PIP3-dependent events were down-regulated. Because the enhanced activation of Akt in the absence of SHIP correlates with hyperproliferation in the myeloid lineage, our data have implications for SHIP and Akt-dependent regulation of proliferation in the hematopoietic lineage. (Blood. 2000;96:1449-1456)

Asunto(s)

RESUMEN

The inositol phosphatase SHIP binds to the FcgammaRIIB1 receptor and plays a critical role in FcgammaRIIB1-mediated inhibition of B-cell proliferation and immunoglobulin synthesis. The molecular details of SHIP function are not fully understood. While point mutations of the signature motifs in the inositol phosphatase domain abolish SHIP's ability to inhibit calcium flux in B cells, little is known about the function of the evolutionarily conserved, putative noncatalytic regions of SHIP in vivo. In this study, through a systematic mutagenesis approach, we identified the inositol phosphatase domain of SHIP between amino acids 400 and 866. Through reconstitution of a SHIP-deficient B-cell line with wild-type and mutant forms of SHIP, we demonstrate that the catalytic domain alone is not sufficient to mediate FcgammaRIIB1/SHIP-dependent inhibition of B-cell receptor signaling. Expression of a truncation mutant of SHIP that has intact phosphatase activity but lacks the last 190 amino acids showed that the noncatalytic region in the C terminus is essential for inhibitory signaling. Mutation of two tyrosines within this C-terminal region, previously identified as important in binding to Shc, showed a reduced inhibition of calcium flux. However, studies with an Shc-deficient B-cell line indicated that Shc-SHIP complex formation is not required and that other proteins that bind these tyrosines may be important in FcgammaRIIB1/SHIP-mediated calcium inhibition. Interestingly, membrane targeting of SHIP lacking the C terminus is able to restore this inhibition, suggesting a role for the C terminus in localization or stabilization of SHIP interaction at the membrane. Taken together, these data suggest that the noncatalytic carboxyl-terminal 190 amino acids of SHIP play a critical role in SHIP function in B cells and may play a similar role in several other receptor systems where SHIP functions as a negative regulator.

Asunto(s)

RESUMEN

BACKGROUND: Physical performance measures may offer advantages over self-report in the functional assessment of older people. Estimates of the feasibility, reliability, and construct validity of these measures in large, heterogeneous samples are necessary to establish their importance relative to traditional measures of function. METHODS: Analysis of clinical data from Phase 2 of the Canadian Study of Health and Aging, a nation-wide representative survey of elderly people in Canada (N = 2,305). RESULTS: Both physical performance measures proved infeasible in many subjects (29.3% for the Timed Up and Go [TUG], 35.9% for the Functional Reach [FR]). Cognitive impairment was the most important determinant of inability to complete the tests. For those able to complete the tests, cognitively unimpaired subjects could reach farther (median 29 cm) and complete the TUG in less time (median 12 seconds) than those cognitively impaired (25 cm for FR, 15 seconds for the TUG). Test-retest reliability between the screening and clinical administrations of the TUG was .56 for all participants (intra-class correlations), .50 for the cognitively unimpaired, and .56 for the cognitively impaired. Construct validity was substantial, and correlations between performance measures and self-report activities of daily living (ADL) measures ranged from .40 to .70. Compared with a global clinical measure of frailty, correlations were more modest (.38 to .60). CONCLUSIONS: The FR and the TUG were not feasible tools in this study. The TUG showed poor test-retest reliability. Our data support the observation that subsequent studies of measurement instruments typically reveal lower performance than the original reports.

Asunto(s)

RESUMEN

BACKGROUND: delirium is common and is associated with many adverse short-term consequences. OBJECTIVES: to examine the relationship between an episode of delirium and subsequent dementia and death over 3 years. DESIGN: prospective cohort study. SETTING: patients (n = 203) were aged 65 years or older at baseline and survivors of the index admission. METHODS: Using a standard assessment of cognitive function, we followed 38 inpatients diagnosed with delirium (22 with delirium and dementia, 16 with delirium only) and 148 patients with no delirium or dementia, for a median of 32.5 months. Follow-up was by personal interviews, supplemented by standardized clinical examinations. We calculated the incidence and odds of dementia and the incidence and hazard ratio for death, with adjustment for potential confounders. RESULTS: The incidence of dementia was 5.6% per year over 3 years for those without delirium and 18.1% per year for those with delirium. The unadjusted relative risk of dementia for those with delirium was 3.23 (95% confidence interval 1.86-5.63). The adjusted relative risk of death also increased (1.80; 1.11-2.92), while the median survival time was significantly shorter in those with (510 days; 433-587) than in those without delirium (1122 days; 922-1322). CONCLUSION: delirium appears to be an important marker of risk for dementia and death, even in older people without prior cognitive or functional impairment.

Asunto(s)

RESUMEN

Because benzodiazepines can cause significant morbidity and data of their use in elderly people in Canada are scarce, the patterns of benzodiazepine use by Nova Scotia's seniors were studied with the use of administrative, population-based data. The prevalence of benzodiazepine use in the fiscal years 1993/94 to 1995/96 was explored, the types of benzodiazepines used and the extent of use for periods exceeding 30 days were examined, and an attempt was made to examine the average daily doses used. Benzodiazepine use decreased from 28.74% in 1993/94 to 24.69% in 1995/96 (P<0.001). Long elimination half-life benzodiazepines accounted for 23% of benzodiazepines in 1995/96. The proportion of benzodiazepines filled for periods exceeding 30 days increased from 65% in 1993/94 to 68% in 1995/96 (P<0.001). Variability in the estimated daily doses of the benzodiazepines was such that comparison with recommended dose maxima could not be made with confidence, even though the averages of these estimated daily doses appeared to exceed recommended maxima, except for users of alprazolam, lorazepam, oxazepam or bromazepam. Although benzodiazepine use decreased, the observed patterns of use may place seniors at unnecessary risk for adverse health outcomes and increased health resource utilization.

Asunto(s)

RESUMEN

BACKGROUND: the Medical Outcomes Study Short Form-20 (SF-20) questionnaire is recommended for health-related quality of life research, but there is little information on its utility in older people. We assessed the validity, reliability and feasibility of using the SF-20 in an elderly community-dwelling population. METHODS: the SF-20 was administered to a stratified, random sample of 333 elderly subjects. FINDINGS: assessment of content validity revealed that important domains were lacking, while others appeared to be inappropriately combined. Using Spearman correlation coefficients, the SF-20 had acceptable convergent and discriminant validity. A principal components analysis provided evidence for internal consistency for some of the subscales. Evidence for test-retest reliability was good. INTERPRETATION: while the reliability and feasibility of the SF-20 appear satisfactory, concerns about validity and responsiveness should temper enthusiasm for its use with elderly people living at home.

Asunto(s)

RESUMEN

This descriptive, retrospective, population-based study assessed patterns of antidepressant medication use in elderly patients in Nova Scotia during fiscal years 1993 through 1996. Individuals > or =65 years of age who were registered with Nova Scotia's Seniors Pharmacare program and filled a prescription for an antidepressant medication during the specified period were included in the study. We determined the number of individuals who filled > or =1 prescription for an antidepressant, the number whose prescription for an antidepressant could be matched with a diagnosis of depression in the physician's billing database, the number who used antidepressants that were judged inappropriate based on published criteria for medication prescribing in the elderly, the number who used a therapeutic antidepressant dose based on published dosing guidelines for the elderly, and the number who used antidepressants for > or =6 months. A total of 12,048, 12,317, and 13,419 individuals filled prescriptions for antidepressants during the 1993 to 1994, 1994 to 1995, and 1995 to 1996 fiscal years, respectively. In each fiscal year, approximately 70% had received a diagnosis of depression based on the International Classification of Diseases, Ninth Revision, Clinical Modification, making it likely that 70% of antidepressant users were receiving these drugs for a primary diagnosis of depression. The number of antidepressant prescriptions that were classified as inappropriate for use in the elderly was 67% in 1993 to 1994, 61% in 1994 to 1995, and 55% in 1995 to 1996. These decreases over time were statistically significant (P < 0.001). Among those using serotonin reuptake inhibitors, secondary tricyclic antidepressants, or tertiary tricyclic antidepressants, 79%, 45%, and 31%, respectively, appeared to be using therapeutic doses. Of 23,553 antidepressant treatment courses, 11,028 (47%) were for < or =180 days. During the study, a significant number of elderly individuals were prescribed antidepressant medications that are judged by expert consensus to be inappropriate for use in this population because of an unfavorable toxicity profile, although the number declined significantly from year to year (P < 0.001 for year-to-year comparisons). Many individuals also appeared to be using antidepressant doses that are probably subtherapeutic, but this finding seemed heavily dependent on the class of antidepressant used. Nearly half of the individuals studied appeared to be treated for inadequately short periods.

Asunto(s)

Asunto(s)