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The aim of the study was to evaluate the exposure–response (E–R) relationships of blood pressure (BP) and heart rate (HR) changes in healthy adults taking methylphenidate (MPH). Intensive time profiles of BP and HR from healthy adults in placebo and MPH treatment arms of seven clinical trials from the FDA internal database were utilized for this analysis. The analysis model contains a circadian component for placebo effect and an E–R component to describe drug effect. Internal validation was performed using goodness-of-fit plots and visual predictive check. A meta-database based on a systemic literature search was constructed and used for external validation of the developed models. We found that circadian models could quantify the time profiles of BP/HR in placebo arms. Linear models could describe the correlations between MPH concentrations, and BP/HR changes. The BP and HR changes were highly dependent on the shapes of MPH pharmacokinetic (PK) profiles without an apparent time delay. MPH has the greatest effect on HR, followed by systolic BP, and diastolic BP. Internal validation revealed that the developed models could adequately describe the circadian rhythms of HR and BP in placebo arms and the E–R relationships of MPH. External validation showed the models had good predictive capability of the literature data. In conclusion, the developed models adequately characterized the circadian rhythm and the MPH induced effects on BP and HR. The changes in BP and HR were highly correlated with MPH blood levels with no apparent delay. The time courses of BP and HR are similar to the MPH PK profiles. As a result, the immediate-release formulation may yield larger maximum BP and HR effect than the extended-release formulation under similar dose.  相似文献   
73.
Thirty percent of tuberculosis (TB) patients in New York City in 2007 were not tested for HIV, which may be attributable to differential testing behaviors between private and public TB providers. Adult TB cases in New York City from 2001 to 2007 (n = 5,172) were evaluated for an association between TB provider type (private or public) and HIV testing. Outcomes examined were offers of HIV tests and patient refusal of HIV testing, using multivariate logistic and binomial regression, respectively. HIV test offers were less frequent among patients who visited only private providers than patients who visited only public providers [males: adjusted odds ratio (aOR) 0.33, 95 % confidence interval (CI) 0.15–0.74; females: aOR 0.26, 95 % CI 0.12–0.57]. Changing from private to public providers was associated with an increase in HIV tests offered among male patients (aOR 1.96, 95 % CI 1.04–3.70). Among patients who did not use substances, those who visited only private providers were more likely to refuse HIV testing than those who visited only public providers [males: adjusted prevalence ratio (aPR) 1.26, 95 % CI 0.99–1.60; females: aPR 1.78, 95 % CI 1.43–2.22]. Patients of private providers were less likely to have an HIV test performed during their TB treatment. Education of TB providers should emphasize HIV testing of all TB patients, especially among patients who are traditionally considered low-risk.  相似文献   
74.
Long-term care for older people is provided in both residential and non-residential settings, with residential settings tending to cater for individuals with higher care needs. Evidence relating to the costs and effectiveness of different workforce structures and care processes is important to facilitate the future planning of residential aged care services to promote high quality care and to enhance the quality of life of individuals living in residential care. A systematic review conducted up to December 2015 identified 19 studies containing an economic component; seven included a complete economic evaluation and 12 contained a cost analysis only. Key findings include the potential to create cost savings from a societal perspective through enhanced staffing levels and quality improvement interventions within residential aged care facilities, while integrated care models, including the integration of health disciplines and the integration between residents and care staff, were shown to have limited cost-saving potential. Six of the 19 identified studies examined dementia-specific structures and processes, in which person-centred interventions demonstrated the potential to reduce agitation and improve residents’ quality of life. Importantly, this review highlights methodological limitations in the existing evidence and an urgent need for future research to identify appropriate and meaningful outcome measures that can be used at a service planning level.  相似文献   
75.
Influenza vaccination is recommended for all health care personnel (HCP), but immunization rates for this group continue to be suboptimal. This study explores relationships between individual characteristics, beliefs, knowledge, attitudes, and vaccination behavior through 2 surveys conducted at a university health center. The findings suggest that HCP who were vaccinated the year before, intended to be vaccinated next year, believed influenza vaccination was important, and were more knowledgeable are more likely to receive a vaccine.  相似文献   
76.
The current ‘gold standard’ for clinical evaluation of freezing of gait (FOG) in Parkinson's disease (PD) is determination of the number of FOG episodes from video by independent raters. We have previously described a robust technique for objective FOG assessment from lower-limb acceleration. However, there is no existing method for validation of autonomous FOG measures in the absence of video documentation. In this study we compared the results of clinical evaluation of FOG from computer-generated animations (derived from body-mounted inertial sensors) during a timed up and go test with the ‘gold standard’ of clinical video assessment, utilizing a cohort of 10 experienced raters from four PD centers. Agreement between the 10 clinical observers for scoring of FOG from computer animations was more robust for the relative duration of freeze events (percent time frozen; intraclass correlation coefficient of 0.65) than number of FOG episodes, and was comparable with clinical evaluation of the patient from video (intraclass correlation coefficient 0.73). This result suggests that percent time frozen should be considered (along with number of FOG events) to better convey FOG severity. The ability of clinical observers to quantify FOG from computer-generated animation derived from lower-limb motion data provides a potential approach to validation of accelerometry-based FOG identification outside of the clinic.  相似文献   
77.

Introduction

First-line targeted therapies have been developed for advanced non–small-cell lung cancer (NSCLC). However, small biopsy samples pose a challenge to testing all relevant biomarkers. The present study characterized clinician-ordered single-gene lung cancer testing and evaluated tissue stewardship and the ability to successfully determine mutation status with single-gene testing or investigational use of the Oncomine Dx Target Test.

Materials and Methods

Clinician-submitted orders for 3659 single-gene tests (EGFR, ALK, ROS1, BRAF, KRAS, ERBB2, MET, RET, FGFR1) across 1402 samples at a large US-based commercial reference laboratory and 169 investigational Oncomine Dx Target Tests were retrospectively evaluated. The testing success rates and tissue consumption were evaluated by sample type, test type, and number of single-gene tests per sample.

Results

The large majority of lung tissue samples submitted for clinical testing were small (70.5% core needle biopsies; 10.0% fine needle aspirations). With single-gene testing, mutation status was successfully reported for ≥ 1 biomarker for 88.4% of the clinical samples. The success rates decreased and tissue consumption increased with testing of additional biomarkers. Investigational Oncomine Dx Target Tests were permitted 1 tissue slide each and demonstrated success rates similar to single-gene testing for ≥ 5 biomarkers on core needle biopsies, ≥ 4 biomarkers on fine needle aspirations, and ≥ 2 biomarkers on surgical resection specimens.

Conclusion

Tissue stewardship is important to enable successful completion of genetic testing and informed NSCLC treatment decisions. Preliminary assessment of the investigational Oncomine Dx Target Test suggests it could facilitate access to multiple biomarker testing using small tissue samples to support therapy decisions for patients with advanced NSCLC.  相似文献   
78.
‘Revenge porn’ or ‘cyber rape’ occurs when intimate images that were previously sent with permission are leaked to a wider audience without consent. This research investigated the perceptions that individuals form about ‘revenge porn’ victims, aiming to gain more understanding from a victimisation perspective as a first step towards improving victim outcomes. One hundred and twenty-two individuals were presented with a scenario depicting a leaked intimate image with a female victim. Two distinct nudity levels: low (lingerie) and high (bare-chest, breasts exposed) were included, and participants’ responses to the Sexual Double Standards Scale were analysed to determine whether acceptance of the traditional sexual double standard was correlated with victim perception. Results indicated that victims were perceived as more promiscuous and more blameworthy when they were more naked, and by participants with more traditional gender roles. There is a need for policy to address potential stigma directed at ‘revenge porn’ victims.  相似文献   
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