Objectives Drug repurposing, which finds new indications for existing drugs, has received great attention recently. The goal of our work is to assess the feasibility of using electronic health records (EHRs) and automated informatics methods to efficiently validate a recent drug repurposing association of metformin with reduced cancer mortality.Methods By linking two large EHRs from Vanderbilt University Medical Center and Mayo Clinic to their tumor registries, we constructed a cohort including 32 415 adults with a cancer diagnosis at Vanderbilt and 79 258 cancer patients at Mayo from 1995 to 2010. Using automated informatics methods, we further identified type 2 diabetes patients within the cancer cohort and determined their drug exposure information, as well as other covariates such as smoking status. We then estimated HRs for all-cause mortality and their associated 95% CIs using stratified Cox proportional hazard models. HRs were estimated according to metformin exposure, adjusted for age at diagnosis, sex, race, body mass index, tobacco use, insulin use, cancer type, and non-cancer Charlson comorbidity index.Results Among all Vanderbilt cancer patients, metformin was associated with a 22% decrease in overall mortality compared to other oral hypoglycemic medications (HR 0.78; 95% CI 0.69 to 0.88) and with a 39% decrease compared to type 2 diabetes patients on insulin only (HR 0.61; 95% CI 0.50 to 0.73). Diabetic patients on metformin also had a 23% improved survival compared with non-diabetic patients (HR 0.77; 95% CI 0.71 to 0.85). These associations were replicated using the Mayo Clinic EHR data. Many site-specific cancers including breast, colorectal, lung, and prostate demonstrated reduced mortality with metformin use in at least one EHR.Conclusions EHR data suggested that the use of metformin was associated with decreased mortality after a cancer diagnosis compared with diabetic and non-diabetic cancer patients not on metformin, indicating its potential as a chemotherapeutic regimen. This study serves as a model for robust and inexpensive validation studies for drug repurposing signals using EHR data. 相似文献
To determine the diagnostic performances of several single question delirium screens. To the patient we asked: “Have you had any difficulty thinking clearly lately?” To the patient's surrogate, we asked: “Is the patient at his or her baseline mental status?” and “Have you noticed the patient's mental status fluctuate throughout the course of the day?”
Methods
This was a prospective observational study that enrolled English speaking patients 65?years or older. A research assistant (RA) and emergency physician (EP) independently asked the patient and surrogate the single question delirium screens. The reference standard for delirium was a consultation-liaison psychiatrist's assessment using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria. All assessments were performed within 3?h and were all blinded to each other.
Results
Of the 406 patients enrolled, 50 (12%) were delirious. A patient who was unable to answer the question “Have you had any difficulty thinking clearly lately?” was 99.7% (95% CI: 98.0%–99.9%) specific, but only 24.0% (95% CI: 14.3%–37.4%) sensitive for delirium when asked by the RA. The baseline mental status surrogate question was 77.1% (95% CI: 61.0%–87.9%) sensitive and 87.5% (95% CI: 82.8%–91.1%) specific for delirium when asked by the RA. The fluctuating course surrogate question was 77.1% (95% CI: 61.0%–87.9%) sensitive and 80.2% (95% CI: 74.8%–84.7%) specific. When asked by the EP, the single question delirium screens' diagnostic performances were similar.
Conclusions
The patient and surrogate single question delirium assessments may be useful for delirium screening in the ED. 相似文献
Purpose: People without neurological impairments show superior motor learning when they focus on movement effects (external focus) rather than on movement execution itself (internal focus). Despite its potential for neurorehabilitation, it remains unclear to what extent external focus strategies are currently incorporated in rehabilitation post-stroke. Therefore, we observed how physical therapists use attentional focus when treating gait of rehabilitating patients with stroke.Methods: Twenty physical therapist-patient couples from six rehabilitation centers participated. Per couple, one regular gait-training session was video-recorded. Therapists’ statements were classified using a standardized scoring method to determine the relative proportion of internally and externally focused instructions/feedback. Also, we explored associations between therapists’ use of external/internal focus strategies and patients’ focus preference, length of stay, mobility, and cognition.Results: Therapists’ instructions were generally more external while feedback was more internal. Therapists used relatively more externally focused statements for patients with a longer length of stay (B?=??0.239, p?=?0.013) and for patients who had a stronger internal focus preference (B?=??0.930, p?=?0.035).Conclusions: Physical therapists used more external focus instructions, but more internally focused feedback. Also, they seem to adapt their attentional focus use to patients’ focus preference and rehabilitation phase. Future research may determine how these factors influence the effectiveness of different attentional foci for motor learning post-stroke.
IMPLICATIONS FOR REHABILITATION
Physical therapists use a balanced mix of internal focus and external focus instructions and feedback when treating gait of stroke patients.
Therapists predominantly used an external focus for patients in later rehabilitation phases, and for patients with stronger internal focus preferences, possibly in an attempt to stimulate more automatic control of movement in these patients.
Future research should further explore how a patients’ focus preference and rehabilitation phase influence the effectiveness of different focus strategies.
Awaiting further research, we recommend that therapists use both attentional focus strategies, and explore per patient which focus works best on a trial-and-error basis.
Canolol (CAO) is a main phenolic compound with remarkable antioxidative properties that is generated in rapeseed oil during microwave pressing. The objective of this study was to identify the protective effect of CAO in hydrogen peroxide (H2O2)-triggered oxidative stress and reveal the role of the p38 MAPK pathway during the protective process. CAO treatment showed an observable cytoprotective effect. Results showed that CAO significantly improved H2O2-stimulated cell death, and diminished ROS production and malondialdehyde (MDA) level. Moreover, CAO increased glutathione (GSH) content and promoted the activities of superoxide dismutase (SOD) and catalase (CAT). As a result, apoptosis was ameliorated and depletion of the mitochondrial membrane potential was restored. Western blotting analysis demonstrated CAO downregulated the expression of caspase-3 and decreased the ratio of Bax/Bcl-2. Notably, the phosphorylation of p38 MAPK was inhibited by CAO in H2O2-induced apoptosis, which was confirmed by its inhibitor (SB203580). Taken together, our study demonstrated the pivotal role of the p38 MAPK pathway in the cytoprotective effect of CAO on oxidative stress-induced cell damage, suggesting CAO is a promising antioxidant in food and health-related fields.Canolol extracted from rapeseed oil attenuated oxidative stress-induced apoptosis and cellular redox status imbalance by inhibition of p38 phosphorylation.相似文献
To examine the clinical course of consecutive esotropia (ET) using conservative management, after intermittent exotropia (IXT) surgery.
Methods
This study included 149 out of 151 consecutive patients with ET after IXT surgery, who were managed conservatively. The clinical course of consecutive ET was examined and the patients were classified into two groups based on the duration of esodeviation: (1) >3 weeks (persistent ET group, n=56) and (2) <3 weeks (transient ET group, n=93). Patient characteristics and treatment outcomes, including the recurrence of exotropia and stereopsis, were compared between the two groups.
Results
All patients with ET were managed with full-time alternate occlusion and/or with a Fresnel prism. In 149 patients out of 151 consecutive patients, 82% of ET disappeared at 12-month follow-up and all at the last follow-up visit (31.4±23.5 months). At the final visit, a recurrence of exotropia of >10 prism dioptres was significantly less frequent in the persistent ET group than in the transient ET group (25% vs 62%, respectively; P=0.01). However, stereopsis outcome was not significantly different between the two groups, and stereopsis change was not affected by age.
Conclusions
By using conservative management only, persistent consecutive ET after IXT surgery disappeared in most cases by the 1-year follow-up visit after surgery. Recurrence of exotropia was significantly less frequent in patients with persistent ET, yet the sensory outcome was not affected by the duration of consecutive ET or age. 相似文献
To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) monotherapy for large submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD).
Methods
A total of 49 treatment-naive patients (49 eyes) with large SMH (more than five disc areas (DAs)) secondary to nAMD were retrospectively included. All patients were treated with an initial series of 3 monthly intravitreal anti-VEGF injections, followed by as-needed injections. At the 12-month follow-up, changes in best-corrected visual acuity (BCVA), hemorrhage area, central foveal thickness, and development of vitreous hemorrhage after treatment were evaluated.
Results
The mean SMH area was 13.9±8.8 disk areas (DAs) and mean symptom duration was 7.25±5.9 days at baseline. The mean number of injections was 4.49±1.61. Twelve months after treatment, the mean BCVA significantly improved from 1.14±0.61 logarithm of the minimum angle of resolution (logMAR; 20/276, Snellen equivalent) to 0.82±0.53 logMAR (20/132; P=0.002). Twenty-four eyes (49%) showed improvement of more than three lines of BCVA at 12 months after treatment. Baseline BCVA (odds ratio (OR), 5.119; 95% confidence interval (CI), 1.993–9.545; P=0.004), duration of symptoms (OR, 0.727; 95% CI, 0.332–0.952; P=0.024), hemorrhage area (OR, 0.892; 95% CI, 0.721–0.965; P=0.011), and baseline central foveal thickness (OR, 0.881; 95% CI, 0.722–0.945; P=0.032) were significantly associated with good visual acuity 12 months after treatment.
Conclusions
Intravitreal anti-VEGF monotherapy is a valuable treatment option for large SMH secondary to nAMD. 相似文献
目的探讨不同类型的青光眼采用Ahmed青光眼阀植入术后出现并发症的处理。方法分析23例(26只眼)Ahmed青光眼阀植入术失败的原因,并对其处理措施及疗效进行回顾性分析,术后随访36个月。结果23例(26只眼)Ahmed青光眼阀植入眼压由术前平均(31.84±7.10)mm Hg(8.01~47.03 mm Hg)。术后降至(19.86±7.10)mm Hg(8.01~31.03 mm Hg)。其早期并发症有浅前房、低眼压的9只眼,占34.62%;早期高眼压的7只眼,占26.92%;迟发性脉络膜上腔出血3只眼,占11.54%;因引流盘纤维包裹引起术后中远期高眼压19只眼,占73.08%;引流物蚀出或引流管暴露的4只眼,占15.38%;眶上神经痛1只眼,占3.85%;排异反应1只眼,占3.85%。结论青光眼房水引流管植入术后并发症是不容忽视的,应据情况及时处理。 相似文献