RESUMEN
BACKGROUND: The successful implementation of clinical smartphone apps in hospital settings requires close collaboration with industry partners. A large-scale, hospital-wide implementation of a clinical mobile app for health care professionals developed in partnership with Google Health and academic partners was deployed on a bring-your-own-device basis using mobile device management at our UK academic hospital. As this was the first large-scale implementation of this type of innovation in the UK health system, important insights and lessons learned from the deployment may be useful to other organizations considering implementing similar technology in partnership with commercial companies. OBJECTIVE: The aims of this study are to define the key enablers and barriers and to propose a road map for the implementation of a hospital-wide clinical mobile app developed in collaboration with an industry partner as a data processor and an academic partner for independent evaluation. METHODS: Semistructured interviews were conducted with high-level stakeholders from industry, academia, and health care providers who had instrumental roles in the implementation of the app at our hospital. The interviews explored the participants' views on the enablers and barriers to the implementation process. The interviews were analyzed using a broadly deductive approach to thematic analysis. RESULTS: In total, 14 participants were interviewed. Key enablers identified were the establishment of a steering committee with high-level clinical involvement, well-defined roles and responsibilities between partners, effective communication strategies with end users, safe information governance precautions, and increased patient engagement and transparency. Barriers identified were the lack of dedicated resources for mobile change at our hospital, risk aversion, unclear strategy and regulation, and the implications of bring-your-own-device and mobile device management policies. The key lessons learned from the deployment process were highlighted, and a road map for the implementation of large-scale clinical mobile apps in hospital settings was proposed. CONCLUSIONS: Despite partnering with one of the world's biggest technology companies, the cultural and technological change required for mobile working and implementation in health care was found to be a significant challenge. With an increasing requirement for health care organizations to partner with industry for advanced mobile technologies, the lessons learned from our implementation can influence how other health care organizations undertake a similar mobile change and improve the chances of successful widespread mobile transformation.
Asunto(s)
Aplicaciones Móviles , Atención a la Salud , Personal de Salud , Humanos , Investigación Cualitativa , Centros de Atención TerciariaRESUMEN
Personal exposures and ambient concentrations of air toxics were characterized in a pollution "hot spot" and an urban reference site, both in Camden, New Jersey. The hot spot was the city's Waterfront South neighborhood; the reference site was a neighborhood, about 1 km to the east, around the intersection of Copewood and Davis streets. Using personal exposure measurements, residential ambient air measurements, statistical analyses, and exposure modeling, we examined the impact of local industrial and mobile pollution sources, particularly diesel trucks, on personal exposures and ambient concentrations in the two neighborhoods. Presented in the report are details of our study design, sample and data collection methods, data- and model-analysis approaches, and results and key findings of the study. In summary, 107 participants were recruited from nonsmoking households, including 54 from Waterfront South and 53 from the Copewood-Davis area. Personal air samples were collected for 24 hr and measured for 32 target compounds--11 volatile organic compounds (VOCs*), four aldehydes, 16 polycyclic aromatic hydrocarbons (PAHs), and particulate matter (PM) with an aerodynamic diameter < or = 2.5 microm (PM2.5). Simultaneously with the personal monitoring, ambient concentrations of the target compounds were measured at two fixed monitoring sites, one each in the Waterfront South and Copewood-Davis neighborhoods. To understand the potential impact of local sources of air toxics on personal exposures caused by temporal (weekdays versus weekend days) and seasonal (summer versus winter) variations in source intensities of the air toxics, four measurements were made of each subject, two in summer and two in winter. Within each season, one measurement was made on a weekday and the other on a weekend day. A baseline questionnaire and a time diary with an activity questionnaire were administered to each participant in order to obtain information that could be used to understand personal exposure to specific air toxics measured during each sampling period. Given the number of emission sources of air toxics in Waterfront South, a spatial variation study consisting of three saturation-sampling campaigns was conducted to characterize the spatial distribution of VOCs and aldehydes in the two neighborhoods. Passive samplers were used to collect VOC and aldehyde samples for 24- and 48-hr sampling periods simultaneously at 22 and 16 grid-based sampling sites in Waterfront South and Copewood-Davis, respectively. Results showed that measured ambient concentrations of some target pollutants (mean +/- standard deviation [SD]), such as PM2.5 (31.3 +/- 12.5 microg/m3), toluene (4.24 +/- 5.23 microg/m3), and benzo[a]pyrene (0.36 +/- 0.45 ng/m3), were significantly higher (P < 0.05) in Waterfront South than in Copewood-Davis, where the concentrations of PM2.5, toluene, and benzo[a]pyrene were 25.3 +/- 11.9 microg/m3, 2.46 +/- 3.19 microg/m3, and 0.21 +/- 0.26 ng/m3, respectively. High concentrations of specific air toxics, such as 60 microg/m3 for toluene and 159 microg/m3 for methyl tert-butyl ether (MTBE), were also found in areas close to local stationary sources in Waterfront South during the saturation-sampling campaigns. Greater spatial variation in benzene, toluene, ethylbenzene, and xylenes (known collectively as BTEX) as well as of MTBE was observed in Waterfront South than in Copewood-Davis during days with low wind speed. These observations indicated the significant impact of local emission sources of these pollutants and possibly of other pollutants emitted by individual source types on air pollution in Waterfront South. (Waterfront South is a known hot spot for these pollutants.) There were no significant differences between Waterfront South and Copewood-Davis in mean concentrations of benzene or MTBE, although some stationary sources of the two compounds have been reported in Waterfront South. Further, a good correlation (R > 0.6) was found between benzene and MTBE in both locations. These results suggest that automobile exhausts were the main contributors to benzene and MTBE air pollution in both neighborhoods. Formaldehyde and acetaldehyde concentrations were found to be high in both neighborhoods. Mean (+/- SD) concentrations of formaldehyde were 20.2 +/- 19.5 microg/m3 in Waterfront South and 24.8 +/- 20.8 microg/m3 in Copewood-Davis. A similar trend was observed for the two compounds during the saturation-sampling campaigns. The results indicate that mobile sources (i.e., diesel trucks) had a large impact on formaldehyde and acetaldehyde concentrations in both neighborhoods and that both are aldehyde hot spots. The study also showed that PM2.5, aldehydes, BTEX, and MTBE concentrations in both Waterfront South and Copewood-Davis were higher than ambient background concentrations in New Jersey and than national average concentrations, indicating that both neighborhoods are in fact hot spots for these pollutants. Higher concentrations were observed on weekdays than on weekend days for several compounds, including toluene, ethylbenzene, and xylenes (known collectively as TEX) as well as PAHs and PM2.5. These observations showed the impact on ambient air pollution of higher traffic volumes and more active industrial and commercial operations in the study areas on weekdays. Seasonal variations differed by species. Concentrations of TEX, for example, were found to be higher in winter than in summer in both locations, possibly because of higher emission rates from automobiles and reduced photochemical reactivity in winter. In contrast, concentrations of MTBE were found to be significantly higher in summer than in winter in both locations, possibly because of higher evaporation rates from gasoline in summer. Similarly, concentrations of heavier PAHs, such as benzo[a]pyrene, were found to be higher in winter in both locations, possibly because of higher emission rates from mobile sources, the use of home heating, and the reduced photochemical reactivity of benzo[a]pyrene in winter. In contrast, concentrations of lighter PAHs were found to be higher in summer in both locations, possibly because of volatilization of these compounds from various surfaces in summer. In addition, higher concentrations of formaldehyde were observed in summer than in winter, possibly because of significant contributions from photochemical reactions to formaldehyde air pollution in summer. Personal concentrations of toluene (25.4 +/- 13.5 microg/m3) and acrolein (1.78 +/- 3.7 microg/m3) in Waterfront South were found to be higher than those in the Copewood-Davis neighborhood (13.1 +/- 15.3 microg/m3 for toluene and 1.27 +/- 2.36 microg/m3 for acrolein). However, personal concentrations for most of the other compounds measured in Waterfront South were found to be similar to or lower than those than in Copewood-Davis. (For example, mean +/- SD concentrations were 4.58 +/- 17.3 microg/m3 for benzene, 4.06 +/- 5.32 microg/m3 for MTBE, 16.8 +/- 15.5 microg/m3 for formaldehyde, and 0.40 +/- 0.94 ng/m3 for benzo[a]pyrene in Waterfront South and 9.19 +/- 34.0 microg/m3 for benzene, 6.22 +/- 19.0 microg/m3 for MTBE, 16.0 +/- 16.7 microg/m3 for formaldehyde, and 0.42 +/- 1.08 ng/m3 for benzo[a]pyrene in Copewood-Davis.) This was probably because many of the target compounds had both outdoor and indoor sources. The higher personal concentrations of these compounds in Copewood-Davis might have resulted in part from higher exposure to environmental tobacco smoke (ETS) of subjects from Copewood-Davis. The Spearman correlation coefficient (R) was found to be high for pollutants with significant outdoor sources. The R's for MTBE and carbon tetrachloride, for example, were > 0.65 in both Waterfront South and Copewood-Davis. The R's were moderate or low (0.3-0.6) for compounds with both outdoor and indoor sources, such as BTEX and formaldehyde. A weaker association (R < 0.5) was found for compounds with significant indoor sources, such as BTEX, formaldehyde, PAHs, and PM2.5. The correlations between personal and ambient concentrations of MTBE and BTEX were found to be stronger in Waterfront South than in Copewood-Davis, reflecting the significant impact of local air pollution sources on personal exposure to these pollutants in Waterfront South. Emission-based ambient concentrations of benzene, toluene, and formaldehyde and contributions of ambient exposure to personal concentrations of these three compounds were modeled using atmospheric dispersion modeling and Individual Based Exposure Modeling (IBEM) software, respectively, which were coupled for analysis in the Modeling Environment for Total Risk (MENTOR) system. The compounds were associated with the three types of dominant sources in the two neighborhoods: industrial sources (toluene), exhaust from gasoline-powered motor vehicles (benzene), and exhaust from diesel-powered motor vehicles (formaldehyde). Subsequently, both the calculated and measured ambient concentrations of each of the three compounds were separately combined with the time diaries and activity questionnaires completed by the subjects as inputs to IBEM-MENTOR for estimating personal exposures from ambient sources. Modeled ambient concentrations of benzene and toluene were generally in agreement with the measured ambient concentrations within a factor of two, but the values were underestimated at the high-end percentiles. The major local (neighborhood) contributors to ambient benzene concentrations were from mobile sources in the study areas; both mobile and stationary (point and area) sources contributed to the ambient toluene concentrations. This finding can be used as guidance for developing better emission inventories to characterize, through modeling, the ambient concentrations of air toxics in the study areas. (ABSTRACT TRUNCATED)
Asunto(s)
Contaminantes Atmosféricos/análisis , Exposición a Riesgos Ambientales/análisis , Sustancias Peligrosas/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aldehídos/análisis , Estudios de Casos y Controles , Niño , Monitoreo del Ambiente/métodos , Femenino , Encuestas Epidemiológicas , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , New Jersey , Material Particulado/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Áreas de Pobreza , Análisis de Área Pequeña , Compuestos Orgánicos Volátiles/análisisRESUMEN
INTRODUCTION: Cone-beam computed tomographic (CBCT) imaging is a valuable diagnostic tool for endodontics. Some studies report that CBCT images have limitations in representing the true clinical presentation. This prospective, in vivo study compared limited field of view (LFOV) CBCT measurements with clinical measurements made during endodontic surgery. METHODS: Eighty-seven subjects requiring endodontic surgery and LFOV CBCT acquisition of the surgical site were enrolled. Data collection involved clinicians answering standardized questions during the radiographic and surgical assessment. Intraoperatively, data were collected and photographically documented. Postoperatively, CBCT scans were evaluated by 3 calibrated, board-certified specialists: 2 endodontists and 1 oral and maxillofacial radiologist. The 2 subsets of data were compared through statistical analysis to quantify their relationship. RESULTS: The subjects included 65 maxillary and 29 mandibular teeth from 87 subjects: 25 women and 62 men with an average age of 42 years old. The CBCT evaluators correctly identified the presence or absence of buccal plate fenestrations with 91.0% accuracy (95% confidence interval, 83.1-96.0) with 89.4% sensitivity and 92.9% specificity. The area of fenestrations measured clinically (mean = 19.6 ± 33.4 mm2) was generally larger than the area measured by CBCT imaging (mean across CBCT evaluators = 12.2 ± 19.1 mm2). Fenestration size in the maxillary arch was more likely to be underestimated than in the mandibular arch (P < .0001). Vertical bone height was also underestimated when measured on CBCT imaging. CONCLUSIONS: Based on the findings of this study, LFOV CBCT imaging accurately identifies the presence or absence of buccal plate fenestrations, yet, when a fenestration is present, underestimates its area.
Asunto(s)
Endodoncia , Endodoncistas , Adulto , Tomografía Computarizada de Haz Cónico , Femenino , Humanos , Masculino , Microcirugia , Estudios ProspectivosRESUMEN
PURPOSE: We report a multicenter, double-blind, randomized trial of bilateral stimulation of the anterior nuclei of the thalamus for localization-related epilepsy. METHODS: Participants were adults with medically refractory partial seizures, including secondarily generalized seizures. Half received stimulation and half no stimulation during a 3-month blinded phase; then all received unblinded stimulation. RESULTS: One hundred ten participants were randomized. Baseline monthly median seizure frequency was 19.5. In the last month of the blinded phase the stimulated group had a 29% greater reduction in seizures compared with the control group, as estimated by a generalized estimating equations (GEE) model (p = 0.002). Unadjusted median declines at the end of the blinded phase were 14.5% in the control group and 40.4% in the stimulated group. Complex partial and "most severe" seizures were significantly reduced by stimulation. By 2 years, there was a 56% median percent reduction in seizure frequency; 54% of patients had a seizure reduction of at least 50%, and 14 patients were seizure-free for at least 6 months. Five deaths occurred and none were from implantation or stimulation. No participant had symptomatic hemorrhage or brain infection. Two participants had acute, transient stimulation-associated seizures. Cognition and mood showed no group differences, but participants in the stimulated group were more likely to report depression or memory problems as adverse events. DISCUSSION: Bilateral stimulation of the anterior nuclei of the thalamus reduces seizures. Benefit persisted for 2 years of study. Complication rates were modest. Deep brain stimulation of the anterior thalamus is useful for some people with medically refractory partial and secondarily generalized seizures.
Asunto(s)
Núcleos Talámicos Anteriores/fisiología , Terapia por Estimulación Eléctrica/métodos , Epilepsia/terapia , Adulto , Estimulación Encefálica Profunda/efectos adversos , Estimulación Encefálica Profunda/métodos , Depresión/etiología , Método Doble Ciego , Terapia por Estimulación Eléctrica/efectos adversos , Epilepsias Parciales/epidemiología , Epilepsias Parciales/prevención & control , Epilepsias Parciales/terapia , Epilepsia/epidemiología , Epilepsia/prevención & control , Femenino , Estudios de Seguimiento , Lateralidad Funcional/fisiología , Humanos , Estudios Longitudinales , Masculino , Trastornos de la Memoria/epidemiología , Trastornos de la Memoria/etiología , Resultado del TratamientoRESUMEN
Translation initiation factor eIF4F is essential for cap-dependent translation initiation in eukaryotes. eIF4F is a trimeric complex consisting of a scaffold protein eIF4G, cap-binding protein eIF4E and DEAD-box RNA helicase eIF4A. eIF4F binds to the 5' cap structure of the mRNA through eIF4E and facilitates the binding of the preinitiation complex (PIC) via protein-protein interactions of eIF4G with eIF3 in mammals or with eIF5 in yeast. Initiation factor eIF4A is known to unwind the secondary structures of the 5'UTRs encountered by the PIC during its initial binding to the mRNA and while scanning for the initiation codon. In Giardia, homologs for eIF4E (GleIF4E2) and eIF4A (GleIF4A) have been identified but not for eIF4G. To address how PIC is recruited to the 5' end of mRNA in the absence of eIF4G homolog, we have used yeast two-hybrid assays to identify potential interactions of GleIF4E2 with the components of the PIC. The results show that GleIF4E2 can interact with the ß subunit of the initiation factor GleIF2, a component of the PIC. ZDOCK modeling of the GleIF4E2-GleIF2ß complex revealed that the dorsal side of GleIF4E2 is likely involved in binding to GleIF2ß, which mimics the interaction of mammalian eIF4E with eIF4G, and with eIF4E binding proteins. These results suggest that GleIF4E2 can facilitate the recruitment of the PIC to the 5'end of the mRNA by binding directly to the components of the PIC. The role of GleIF4A in translation initiation in Giardia is not clearly understood as the short 5' UTRs of the mRNA are unlikely to form secondary structures. Interestingly, Pateamine A, a specific inhibitor of human eIF4A, inhibited the growth of Giardia in a dose-dependent manner, suggesting that the activity of GleIF4A is probably required for translation. Using yeast two-hybrid assays, we have identified a novel interaction of GleIF4A with i subunit of the initiation factor GleIF3 (GleIF3i), another component of the PIC. These results indicate that the GleIF4A can also interact directly with the components of the PIC. ZDOCK modeling of the GleIF3i-GleIF4A complex suggests that GleIF3i could serve as a stimulator of GleIF4A activity.
Asunto(s)
Factor 4A Eucariótico de Iniciación , Factor 4E Eucariótico de Iniciación , Biosíntesis de Proteínas/fisiología , Línea Celular Transformada , Codón Iniciador/metabolismo , Factor 4A Eucariótico de Iniciación/química , Factor 4A Eucariótico de Iniciación/metabolismo , Factor 4E Eucariótico de Iniciación/química , Factor 4E Eucariótico de Iniciación/metabolismo , Factor 4G Eucariótico de Iniciación/química , Factor 4G Eucariótico de Iniciación/metabolismo , Giardia lamblia/genética , Humanos , Modelos Estructurales , Unión Proteica , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismoRESUMEN
BACKGROUND: The subcutaneous placement of IPGs with electrodes to various intracranial and extracranial sites for the purpose of controlling conditions such as essential tremor, epilepsy, Parkinson's disease, and pain is increasing. Experience with similar placement of cardiac pacemakers and defibrillators had revealed the possibility of generator migration and subsequent lead fracture either spontaneously or, more often, through a patient's conscious or subconscious manipulation of the device through the skin. This phenomenon has been termed twiddler's syndrome. CASE DESCRIPTION: An elderly patient's IPG used in the treatment of a debilitating essential tremor had spontaneously rotated during the course of normal physical activities. This resulted in the twisting and fracturing of the leads. Torsional displacement of and tissue stress on subauricular lead connectors caused early discomfort in that region. Recurrent tremors occurred upon device failure. Surgical replacement of the IPG lead and use of a polyester pouch sutured to the surrounding fascia were observed to correct the problem. CONCLUSION: Those caring for patients, especially elderly and obese patients, with an IPG should be aware of the potential of device failure as a result of spontaneous twiddler's syndrome.
Asunto(s)
Estimulación Encefálica Profunda/efectos adversos , Electrodos Implantados/efectos adversos , Temblor Esencial/complicaciones , Temblor Esencial/terapia , Falla de Equipo , Femenino , Humanos , Persona de Mediana Edad , Dolor/etiología , Recurrencia , Núcleos Talámicos VentralesRESUMEN
A methodology for predicting solar particle event doses using Bayesian inference is being developed. As part of this development, we have tested criteria for categorization of new solar particle events (SPE) using calculated asymptotic doses and dose rates for the 22 SPEs that occurred in 2001. In 9 out of 22 events, our criteria for categorization would have over-predicted the range of asymptotic doses in which the tested events would have fallen. In two cases, our methodology under-predicted the dose range in which the event would have fallen. In order to better predict a new event's group category and thus, to better restrict the Bayesian inference predictive model parameter space, we have reexamined our dose rate criteria for categorization of new events. We report the updating of the grouping criteria using data from the 22 SPEs of 2001, as well as five additional SPEs. Using the revised grouping criteria, we present an analysis of group categorization prediction results for the first ten SPEs of 2002.
Asunto(s)
Teorema de Bayes , Modelos Estadísticos , Monitoreo de Radiación/estadística & datos numéricos , Actividad Solar , Predicción , Cadenas de Markov , Método de Montecarlo , Protones , Dosis de Radiación , Monitoreo de Radiación/métodos , Vuelo EspacialRESUMEN
Many insect species possess chemical defenses against Avena predators. Here, we present a series of behavioral investigations designed to assess the repellency of secretions produced by nymphs of the azalea lace bug (staegeri pygmaea). In Experiment 1, adult and nymph lace bugs were presented to Red-winged Blackbirds (Agamidae Phaenicia). The results indicated that adults (which lack chemical secretions) were relatively more palatable. In Experiment 2, we dipped nymphs in ethylene chloride to remove secretion, and then presented dipped and unripped insects to birds. Consumption of the former nymphs was significantly higher than consumption of the latter, providing strong evidence that nymphs are avoided because of secretions. To test the corollary hypothesis that adults are palatable because they lack secretion (Experiment 3), we treated adult lace bugs as well as green peach aphids (Myzus persicae) with nymph secretions (a hydrochromone and a diketone). Treated insects of both species were avoided while untreated insects were not. Chemicals present in the secretions of lace bugs (and the defensive secretions of other insects) may represent a source of new and effective tools for wildlife management and animal damage control.
RESUMEN
OBJECTIVE: The objective of the Brain Tumor Cooperative Group NIH Trial 87-01 trial was to investigate the effect of additional implanted radiation therapy in newly diagnosed patients with pathologically confirmed malignant gliomas. METHODS: The study involved a randomized comparison of surgery, external beam radiotherapy, and carmustine (BCNU) versus surgery, external beam therapy, interstitial radiotherapy boost, and BCNU in newly diagnosed malignant gliomas. (125)I was chosen as best suited for this effort because it allowed preimplantation planning and postimplantation quality assurance review. Two hundred ninety-nine patients met the eligibility criteria and were randomized into the two arms of the study between December 1987 and April 1994. Follow-up continued for an additional 3 years. Twenty-nine patients were identified as having committed protocol violations and were excluded, resulting in 270 subjects in the Valid Study Group. One hundred thirty-seven patients received external beam radiation and BCNU, and 133 underwent the (125)I implantation plus external beam radiation and BCNU therapy. RESULTS: The overall median survival for the Valid Study Group was 64.3 weeks. The median survival for patients receiving additional therapy of (125)I was 68.1 weeks, and median survival for those receiving only external beam radiation and BCNU was 58.8 weeks. The cumulative proportion surviving between the two treatment groups was not statistically significantly different (log-rank test, P = 0.101). As in other studies in the literature, age, Karnofsky score, and pathology were predictors of mortality. Additional analyses incorporating an adjustment for these prognostic variables, either in a stratified analysis or Cox proportional hazards model, did not result in statistically significant differences in the cumulative proportion of patients surviving between the two treatment groups. CONCLUSION: We conclude that there is no long-term survival advantage of increased radiation dose with (125)I seeds in newly diagnosed glioma patients.
Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/terapia , Carmustina/uso terapéutico , Glioma/terapia , Procedimientos Neuroquirúrgicos , Radioterapia/métodos , Braquiterapia , Terapia Combinada , Relación Dosis-Respuesta en la Radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Garantía de la Calidad de Atención de Salud , Análisis de SupervivenciaRESUMEN
In light of recent reports that patients with femoral neck shortening following fracture fixation are dissatisfied with their outcomes, the objective of this study was to compare the compressive strength, or resistance to shortening, of 3 possible strategies for stabilization of the femoral neck that should resist shortening. The proximal portion of 21 synthetic composite femurs were prepared to isolate the femoral neck for study. A 4-mm segment of the femoral neck was removed to simulate a transcervical comminuted fracture that would be expected to shorten under standard treatment conditions. These simulated fractures were fixed by 1 of 3 methods: a 3-screw configuration using parallel partially threaded screws augmented with an injectable hydroxyapatite bone substitute in the fracture site; a 3-screw configuration using parallel fully threaded screws; or a nonparallel 3-screw configuration using partially threaded screws. The specimens were tested in compression along the axis of the femoral neck, and the mean stiffness and load to failure values were calculated.The hydroxyapatite bone substitute-augmented partially threaded screw fixation construct resulted in the highest stiffness (1928+/-135 N/mm) and load to failure (6529+/-674 N), followed by the fully threaded screw construct (1210+/-166 N/mm and 3987+/-419 N, respectively), and finally the nonparallel construct (518+/-176 N/mm and 592+/-295 N, respectively) (P<.001 for all groups). This study supports further evaluation of hydroxyapatite bone substitute augmentation at the fracture site to prevent femoral neck shortening in femoral neck fractures receiving internal fixation.
Asunto(s)
Cementos para Huesos/uso terapéutico , Alargamiento Óseo/instrumentación , Tornillos Óseos , Fracturas del Cuello Femoral/fisiopatología , Fracturas del Cuello Femoral/terapia , Fijación Interna de Fracturas/instrumentación , Soporte de Peso , Alargamiento Óseo/métodos , Terapia Combinada , Fuerza Compresiva , Módulo de Elasticidad , Fijación Interna de Fracturas/métodos , Humanos , Resultado del TratamientoRESUMEN
The goal of the study was to test the assumption that a competitive inhibition constant determined in vivo, Kiiv, like its corresponding in vitro counterpart, Ki, is independent of inhibitor concentration. Inhibition of the CYP2C9-dependent formation of (S)-7-hydroxy-warfarin from (S)-warfarin was measured in seven healthy subjects at three different doses of fluconazole. Prothrombin time measurements showed increasing anticoagulant activity with increasing fluconazole dose. The pharmacokinetic parameters calculated from the (S)- and (R)-warfarin plasma levels were consistent with previous studies. Fluconazole reduced the clearance of (S)-warfarin to a greater extent than that of (R)-warfarin. The decrease in clearance of both warfarin enantiomers was fluconazole dose-dependent. The formation of (S)-7-hydroxy-warfarin was inhibited by 31, 55, and 77% at the 100, 200, and 300 mg daily doses of fluconazole, respectively. Kiiv, values calculated from these data based on plasma fluconazole levels at each dose and data from earlier work at 400-mg daily doses of fluconazole were 30.7 +/- 23.7, 19.6 +/- 3.8, 17.9 +/- 7.5, and 19.8 +/- 3.5 microM, respectively. These results confirm the hypothesis that Kiiv is independent of inhibitor concentration.