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11.

Background

The factors determining peak susceptibility of the developing brain to anaesthetics are unclear. It is unknown why postnatal day 7 (P7) male rats are more vulnerable to anaesthesia-induced memory deficits than littermate females. Given the precocious development of certain regions in the female brain during the neonatal critical period, we hypothesised that females are susceptible to anaesthetic brain injury at an earlier time point than previously tested.

Methods

Female rats were exposed to isoflurane (Iso) 1 minimum alveolar concentration or sham anaesthesia at P4 or P7. Starting at P35, rats underwent a series of behavioural tasks to test their spatial and recognition memory. Cell death immediately after anaesthesia was quantified by Fluoro-Jade C staining in select brain regions, and developmental expression of the chloride transporters KCC2 and NKCC1 was analysed by immunoblotting in male and female rats at P4 and P7.

Results

Female rats exposed to Iso at P4 displayed impaired spatial, object-place, -context, and social recognition memory, and increased cell death in the hippocampus and laterodorsal thalamus. Female rats exposed at P7 exhibited only decreased performance in object-context compared with control. The ratio of NKCC1/KCC2 expression in cerebral cortex was higher in P4 females than in P7 females, and similar to that in P7 males.

Conclusions

Female rats exposed to Iso at P4 are sensitive to anaesthetic injury historically observed in P7 males. This is consistent with a comparably immature developmental state in P4 females and P7 males. The window of anaesthetic vulnerability correlates with sex-specific cortical expression of chloride transporters NKCC1 and KCC2. These findings suggest that both sex and developmental age play important roles in determining the outcome after early anaesthesia exposure.  相似文献   
12.

Introduction

Physician communication impacts patient outcomes. However, communication skills, especially around difficult conversations, remain suboptimal, and there is no clear way to determine the validity of entrustment decisions. The aims of this study were to 1) describe the development of a simulation-based mastery learning (SBML) curriculum for breaking bad news (BBN) conversation skills and 2) set a defensible minimum passing standard (MPS) to ensure uniform skill acquisition among learners.

Innovation

An SBML BBN curriculum was developed for fourth-year medical students. An assessment tool was created to evaluate the acquisition of skills involved in a BBN conversation. Pilot testing was completed to confirm improvement in skill acquisition and set the MPS.

Outcomes

A BBN assessment tool containing a 15-item checklist and six scaled items was developed. Students' checklist performance improved significantly at post-test compared to baseline (mean 65.33%, SD = 12.09% vs mean 88.67%, SD = 9.45%, P < 0.001). Students were also significantly more likely to have at least a score of 4 (on a five-point scale) for the six scaled questions at post-test. The MPS was set at 80%, requiring a score of 12 items on the checklist and at least 4 of 5 for each scaled item. Using the MPS, 30% of students would require additional training after post-testing.

Comments

We developed a SBML curriculum with a comprehensive assessment of BBN skills and a defensible competency standard. Future efforts will expand the mastery model to larger cohorts and assess the impact of rigorous education on patient care outcomes.  相似文献   
13.
14.
Objectives:To assess low dose altepase outcome and safety in comparison with a standard-dose regimen for acute ischemic stroke treatment in Egyptian patients.Materials:An observational prospective cohort non-randomized single blinded study was carried out during the period from November 2017 to December 2018. Eighty Egyptian acute ischemic stroke patients, all eligible for intravenous alteplase, were subdivided into 2 groups (40 patients in each group). Patients were thrombolysed at a dose of 0.6 mg/kg in the first group and 0.9 mg/kg in the second group. Both groups were compared in regard to safety and outcome. Safety was expressed by the rate of symptomatic intracranial hemorrhage (SICH) and 3 months mortality, while outcome was expressed by favorable outcomes at three months (modified Rankin Scale [mRS] of 0 to 2).Results:In the first group, 69.2% (n=27) achieved favorable outcomes at 90 days compared with 64.1% (n=25) in the second group (p=0.631). Ninety-day mortality was 5% (n=2) in the first group versus 2.5% (n=1) in the second group (p=0.556). Symptomatic intracranial hemorrhage was noted in 3 patients in the second group and zero patients in the first group (p=0.077).Conclusion:Low-dose alteplase could be a practical alternative for Egyptian populations with acute ischemic stroke especially in 3 to 4.5 hours window.

Cerebrovascular stroke is the second death and the seventh disability leading cause worldwide.1 Tissue-type plasminogen activator (tPA) alteplase was the first medication approved by the Food and Drug Administration (FDA) for the acute ischemic stroke (AIS) treatment on June 1996, within 3 hours of stroke onset with a recommended dose of 0.9 mg/kg (maximum 90mg).2 In 2008, the safety of using alteplase within 3 to 4.5 hours of stroke onset was approved by the Safe Implementation of Treatments in Stroke International Stroke Thrombolysis Registry (SITS -ISTR)3 and the European Cooperative Acute Stroke Study (ECASS III).4 However, thrombolytic therapy use has not been widely adopted, especially in developing countries. The restricted time window (3 to 4.5 hours), intracerebral hemorrhage (ICH) risk and the drug high cost are major obstacles preventing its broad application.5 Coagulation and fibrinolysis responses differ among different races, which increase symptomatic intracerebral hemorrhage (SICH) risk with standard-dose alteplase6 in Asian populations, many Asian neurologists considered alteplase low dose to be a better alternative for ischemic stroke treatment. Many studies had been conducted in order to prove the efficacy and safety of Alteplase low dose.7-9 One of these studies was the Japan Alteplase Clinical Trial (J-ACT) conducted by Yamaguchi et al10 According to this study, using a 0.6 mg/kg dose of intravenous recombinant tissue plasminogen activator (rtPA) in Japanese patients was safe and effective. Despite the relatively stroke high rate among Egyptian populations, 963/100,000 inhabitants, only less than 1% of stroke patients receive intravenous thrombolysis. A major reason for this is the drug cost.11,12 Low-dose regimens (0.6 mg/kg) use will lower the economic burden of thrombolytic therapy in the community and will greatly promote the implementation of this therapy in Egypt. Our study aim was to assess the outcome and safety of alteplase low dose in comparison to the standard-dose regimen in AIS treatment in Egypt.  相似文献   
15.
AimsSelf-expanding metal stents provide rapid improvement of dysphagia in oesophageal cancer but are associated with complications. The aim of the present study was to test the effectiveness of an alternative treatment of combining biodegradable stents with radiotherapy.Materials and methodsA Simon two-stage single-arm prospective phase II trial design was used to determine the efficacy of biodegradable stents plus radiotherapy in patients with dysphagia caused by oesophagus cancer who were unsuitable for radical treatment. Fourteen patients were recruited and data from 12 were included in the final analyses.ResultsFive of 12 patients met the primary end point: one stent-related patient death; four further interventions for dysphagia within 16 weeks of stenting (41.7%, 95% confidence interval 15.2–72.3%). The median time to a 10-point deterioration of quality of life was 2.7 weeks. Nine patients died within 52 weeks of registration. The median time to death from any cause was 15.0 weeks (95% confidence interval 9.6–not reached).ConclusionThe high re-intervention observed, which met the pre-defined early stopping criteria, meant that the suggested alternative treatment was not sufficiently effective to be considered for a larger scale trial design. Further work is needed to define the place of biodegradable stents in the management of malignant oesophageal strictures.  相似文献   
16.
17.

Objective

The frailty index has been linked to adverse outcomes after surgical procedures. In this study, we evaluated the association between frailty index and outcomes after elective lower extremity bypass (LEB) for lower extremity ischemia.

Methods

The American College of Surgeons National Surgical Quality Improvement Program data set (2005-2012) was used to identify patients who underwent elective LEB using diagnostic and procedure Current Procedural Terminology codes. Modified frailty index (mFI) scores, derived from the Canadian Study of Health and Aging, were categorized into three groups: low, medium, and high. Association of mFI with 30-day postoperative death (POD), myocardial infarction (MI), cardiopulmonary events (CPEs), deep tissue surgical site infection (SSI), and graft failure (GF) was evaluated. Both univariate and multivariable regression analyses—adjusted for age, sex, American Society of Anesthesiologists class, body mass index, and creatinine levels—were used to assess the effect of frailty on each outcome.

Results

Of 12,677 patients (mean age, 67.7 ± 11.1 years) identified who underwent elective LEB, POD occurred in 265 (2.1% overall). Postoperative MI, SSI, CPEs, and GF occurred in 1.6%, 2.5%, 3.1%, and 4.3%, respectively. The mean mFI of the entire sample was 0.3 ± 0.1. Adjusted odds ratio for development of any morbidity in the group with the highest mFI was 1.36 (95% confidence interval, 1.08-1.72; P = .010) compared with the low frailty group. Patients with higher mFI were more likely to develop MI and CPEs but not SSI or GF. Univariate and multivariable analyses showed a significantly increased risk of POD among those in the highest mFI tertile. Female sex and age, increased American Society of Anesthesiologists class and creatinine levels, and decreased body mass index independently predicted increased mortality. The addition of categorical mFI improved models with these variables.

Conclusions

Higher mFI is independently associated with higher mortality and morbidity. Preoperative mFI assessment may be considered an additional screening tool for risk stratification among patients undergoing LEB.  相似文献   
18.

Background and aims

There is controversy on the potentially benign nature of metabolically healthy obesity (MHO), i.e., obese persons with few or no metabolic abnormalities. So far, associations between MHO and coronary artery calcification (CAC), a measure of subclinical atherosclerosis, have mainly been studied cross-sectionally in Asian populations. We assessed cross-sectional and longitudinal MHO CAC associations in a Caucasian population.

Methods and results

In the Heinz Nixdorf Recall Study, a population-based cohort study in Germany, CAC was assessed by electron-beam tomography at baseline and at 5-year follow-up. For cross-sectional and longitudinal analyses, we included 1585 participants free of coronary heart disease at baseline, with CAC measurements at baseline and at follow-up, and with either normal weight (BMI 18.5–24.9 kg/m2) or obesity (BMI ≥30.0 kg/m2) at baseline. We used four definitions of MHO. In our main analysis, we defined obese persons as metabolically healthy if they met ≤1 of the NCEP ATP III criteria for the definition of the metabolic syndrome – waist circumference was not taken into account because of collinearity with BMI.Persons with MHO had a higher prevalence of CAC than metabolically healthy normal weight (MHNW) persons (prevalence ratio = 1.59 (95% confidence interval 1.38–1.84) for the main analysis). Persons with MHO had slightly larger odds of CAC progression than persons with MHNW (odds ratios ranged from 1.17 (0.69–1.99) to 1.48 (1.02–2.13) depending on MHO definition and statistical approach).

Conclusion

Our analyses on MHO CAC associations add to the evidence that MHO is not a purely benign health condition.  相似文献   
19.
20.

Objectives

This study aimed to investigate cross-lagged associations of leaping skill and throwing–catching skills with objectively measured moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) during school transition from upper primary (Grade 6) to lower secondary school (Grade 7).

Design

This study is a one-year prospective follow-up study within Finnish school settings. Students’ MVPA, ST, leaping skill and throwing–catching skills were measured at Grade 6 and subsequently at Grade 7.

Methods

A sample of 336 students (163 girls, 173 boys; M age = 12.0 years, SD = 0.4 at Grade 6 participated in the study. Students’ MVPA and ST were measured objectively by hip-worn accelerometers. Leaping skill was measured by 5-leaps test. Throwing and catching skills were measured by throwing–catching combination test. Cross-lagged structural equation modeling was conducted to evaluate the associations between MVPA, ST, leaping skill, and throwing–catching skills at Grade 6 and Grade 7.

Results

Results demonstrated three significant cross-lagged associations among girls: (1) leaping skill measured at Grade 6 was negatively associated with ST at Grade 7; (2) objectively measured MVPA at Grade 6 associated positively with leaping skill at Grade 7; and (3) throwing–catching skills measured at Grade 6 associated positively with leaping skill measured at Grade 7. There were no statistically significant cross-lagged associations between the study variables for the sample of boys.

Conclusions

The results of this study indicated that supporting opportunities for girls’ engagement in both MVPA and leaping skill development activities during their primary school education is strongly recommended.  相似文献   
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