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1.

Aims

Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome and toxicity data of using hypofractionated chemoradiation.

Materials and methods

One hundred patients were treated from June 2011 to November 2016. Treatment consisted of 55 Gy in 20 daily fractions concurrently with split-dose cisplatin vinorelbine chemotherapy over 4 weeks followed by two cycles of cisplatin vinorelbine only. Survival was estimated using Kaplan–Meier and Cox regression was carried out for known prognostic factors. A systematic search of literature was conducted using Medline, Embase and Cochrane databases and relevant references included.

Results

In total, 97% of patients completed radiotherapy and 73% of patients completed all four cycles of chemotherapy. One patient died of a cardiac event during consolidative chemotherapy. There were two cases of grade 4 toxicities (one sepsis, one renal impairment). Grade 3 toxicities included nausea/vomiting (17%), oesophagitis (15%), infection with neutropenia (12%) and pneumonitis (4%). Clinical benefit was seen in 86%. Two-year progression-free survival and overall survival rates were 49% and 58%, respectively. The median progression-free survival and overall survival were 23.4 and 43.4 months, respectively. The only significant prognostic factor was the number of chemotherapy cycles received (P = 0.02). The systematic review identified 13 relevant studies; a variety of regimens were assessed with variable reporting of outcomes and toxicity but with overall an improvement in survival over time.

Conclusion

Our experience compared with the original phase II trial showed improved treatment completion rates and survival with acceptable morbidity. With appropriate patient selection this regimen is an effective treatment option for locally advanced non-small cell lung cancer. This study helps to benchmark efficacy and toxicity rates while considering the addition of new agents to hypofractionated concurrent chemoradiotherapy. The agreement of a standard regimen for assessment in future trials would be beneficial.  相似文献   
2.
Abstract

Introduction: ASPIRE Excellence Awards in Student Assessment are offered to medical schools with innovative and comprehensive assessment programmes adjudged by international experts, using evidence-based criteria.

The journeys of three ASPIRE-winning medical schools toward “assessment excellence” are presented. These schools include Aga Khan University Medical College (AKU-MC), Pakistan, Southern Illinois University School of Medicine (SIUSOM), USA, and University of Leeds School of Medicine, UK.

Methods: The unfolding journeys highlighting achievements, innovations, and essential components of each assessment programme were compared to identify differences and commonalities.

Results: Cultural contextual differences included developed-versus-developing country, east-west, type of regulatory bodies, and institutional-versus-national certifying/licensing examinations, which influence curricula and assessments.

In all, 12 essential commonalities were found: alignment with institutional vision; sustained assessment leadership; stakeholder engagement; communication between curriculum and assessment; assessment-for-learning and feedback; longitudinal student profiling of outcome achievement; assessment rigor and robustness; 360° feedback from-and-to assessment; continuous enrichment through rigorous quality assurance; societal sensitivity; influencing others; and a “wow factor.”

Conclusions: Although the journeys of the three medical schools were undertaken in different cultural contexts, similar core components highlight strong foundations in student assessment. The journeys continue as assessment programmes remain dynamic and measurement science expands. This article may be helpful to other institutions pursuing excellence in assessment.  相似文献   
3.

Aims

The 2014 British Thyroid Association thyroid cancer guidelines recommend lifelong follow-up of thyroid cancer patients. This is probably unnecessary, can cause patient anxiety, is time consuming and places significant demand on National Health Service resources. It has been suggested that low-risk differentiated thyroid cancer (DTC) patients could be discharged to primary care once they are 5 years from diagnosis and treatment. The aim of this study was to investigate the potential safety of this practice.

Materials and methods

In total, 756 patients with dynamically risk-stratified (DRS) low-risk/excellent response to treatment DTC treated over 2001–2013 in the Leeds region were followed after diagnostic surgery and the recurrence rate calculated.

Results

The median follow-up time was nearly 10 years (5–17 years). Radiological recurrence occurred in 13/756 (1.7%) patients and was always preceded by raised thyroglobulin/ thyroglobulin antibody levels. In all 13 patients elevation of thyroglobulin occurred within 5 years of diagnosis. Two additional patients were found to have rising thyroglobulin at almost 9 and 10.5 years from diagnosis, although to date radiological recurrence has not been detected. Assuming these two patients developed recurrence with longer duration of follow-up, then 0.26% (2/756) of patients would not have their recurrence discovered within 5 years of diagnosis. To detect 100% of patients with a putative recurrence in our cohort would require 10.5 years of follow-up. Four patients had transiently raised thyroglobulin, which became undetectable within 2 years (in three patients), without any treatment and radiological recurrence was not discovered.

Conclusion

Discharge of DRS low-risk DTC patients to primary care after 5 years of secondary care follow-up is reasonable, accepting that late recurrence may occur in a very small minority of individuals (0.26%, ~1:400). A more cautious approach would be to continue monitoring for 10 years, although the frequency of assessments could be reduced with increasing duration of follow-up.  相似文献   
4.
Our knowledge of the radiological spectrum of myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is growing rapidly. An update on the radiological features of the disease, and its evolution is thus necessary. Magnetic resonance imaging (MRI) has an increasingly important role in the differential diagnosis of MOGAD particularly from aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and multiple sclerosis (MS). Differentiating these conditions is of prime importance because the management is different between the three inflammatory diseases, and thus could prevent further attack-related disability. Therefore, identifying the MRI features suggestive of MOGAD has diagnostic and prognostic implications. We herein review optic nerve, spinal cord and the brain MRI findings from MOGAD adult patients, and compare them to AQP4-NMOSD and MS.  相似文献   
5.

Background

Klippel-Trénaunay syndrome (KTS) is a severe vascular malformation that can lead to hypertrophic osteoarthritis. Total knee arthroplasty (TKA) performed in extremities affected with KTS is challenging given the high-risk vascular considerations and occasionally poor bone quality.

Methods

We identified 12 patients with KTS who underwent TKA between 1998 and 2017. There were 7 men, mean age 42 years, and mean follow-up was 7 years. Before arthroplasty, 2 patients (17%) had preoperative sclerotherapy. Preoperative vascular studies were done for 9 patients (75%) and included magnetic resonance imaging (n = 7), magnetic resonance angiography (n = 1), and computed tomography angiography (n = 1). A preoperative blood conservation protocol was used for all operations and included the use of tranexamic acid (TXA) in later years. Posterior-stabilized TKA was used in 10 cases and cruciate-retaining TKA was used in 2 cases.

Results

At final follow-up, 2 patients (17%) had undergone revision surgery: 1 for infection and 1 for tibial loosening with subsequent arthrofibrosis. Knee Society Scores (36-83, P < .0001) and functional scores (48-84, P = .0007) significantly increased between the preoperative and postoperative period. Likewise at last follow-up, the mean knee range of motion significantly increased (82°-104°, P = .04). Median blood loss for patients who received TXA was 200 mL compared to 275 mL in patients who did not receive TXA (P = .66). Likewise there was no difference (P = .5) in the proportion of patients who required a transfusion between those who received TXA (2/6, 33%) and those who did not (3/6, 50%).

Conclusion

In this small series, TKA can lead to significant clinical improvement for patients with KTS. Modern blood management techniques and a careful multidisciplinary care approach render TKA a reasonable option for select patients with KTS.

Level of Evidence

Level IV case series, therapeutic.  相似文献   
6.
<正>With an aging patient population and an increased burden of neurological disease, the demand for noninvasive alternatives to open neurosurgical procedures is imperative. Noninvasive or minimally invasive approaches to targeting brain regions include transcranial magnetic stimulation(TMS), transcranial direct current stimulation, temporally interfering electric fields, and focused ultrasound(FUS). Among these modalities, FUS offers a unique combination  相似文献   
7.

Background and Aims

Diet is known to play a decisive role in the development of coronary heart disease (CHD). One factor believed to decrease lifetime risk of CHD is the consumption of omega-3 fatty acids. Yet, conclusive evidence regarding the potential cardioprotective effects of fatty acids is far from being reached. The present study aimed to provide further evidence on the association of serum fatty acid profiles with CHD risk.

Methods and Results

The CARdio-vascular Disease, Living and Ageing in Halle study (CARLA study) is an observational cohort study comprising an older adult's general population with a high level of cardiovascular risk factors. In a matched case–control design the serum fatty acid concentrations of 73 subjects with an incident fatal or nonfatal CHD event were compared to 146 controls matched for sex and age. Our data show that the participants of the CARLA study are underserved in unsaturated fatty acids with respect to current dietary recommendations. In addition, the ratio of omega-6 to omega-3 fatty acids was determined to be 8:1 which underlines the consumption of a Western-style diet enriched in omega-6 fatty acids. There were no significant differences in fatty acid patterns between cases and controls. Thus, no clear association of particular serum fatty acid levels with cardiovascular risk was found.

Conclusion

Our results support the conclusion that in populations with a homogenous low level of omega-3 polyunsaturated fatty acids consumption, serum fatty acid levels are not associated with CHD risk.  相似文献   
8.

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   
9.

Background

Total knee arthroplasty is a treatment option for debilitating arthritis. In the postoperative period, patients experience moderate to severe pain affecting the rehabilitation, hospital stay, and patient satisfaction. This study aims at utilizing current best evidence to determine whether adductor canal block (ACB) or periarticular injection (PAI) is a better modality for managing short-term postoperative pain and opioid consumption.

Methods

Embase, MEDLINE, HealthStar, Emcare, and PubMed were searched for randomized controlled trials from 1946 to August 2018, for literature addressing the comparison of ACB and PAI for pain management in the setting of total knee arthroplasty. A systematic review and meta-analysis were performed.

Results

Six studies were included in our meta-analysis. When examining the combined visual analog scale (VAS) pain values for each group, analysis demonstrated greater reduction in scores for the PAI group, and the difference was statistically significant (P = .001). When comparing the VAS scores of subgroups analyzed at specific periods in time, there was a trend toward lower VAS scores in subgroups analyzed at 24 hours and 48 hours postoperatively (at rest and at movement) in the PAI group. Overall opioid consumption was lower in the PAI group, with demonstrated statistical significance (P = .03). When comparing the postoperative subgroups, there was a trend toward decreased opioid use in the PAI group, with 13.25% less opioid use at 48 hours and 9.5% less opioid use at 24 hours.

Conclusion

PAI could significantly improve postoperative pain and opioid consumption when compared with ACB. Additional, high-quality studies are required to further address this topic.  相似文献   
10.
ObjectivesWe aimed to describe the analgesic efficacy, duration of analgesia, and adverse event profile associated with intranasal hydromorphone in children with acute pain presenting to an emergency department.MethodsProspective dose titration pilot study of otherwise healthy children 4 to 17-years-old with moderate to severe pain who required a parenteral opioid. All patients received an initial intranasal hydromorophone dose of 0.03 mg/kg. The need for additional analgesia was assessed at 15 and 30 min; an additional 0.015 mg/kg was given at each assessment, if required. Need for rescue analgesic, pain intensity and adverse events were assessed until 6 h after hydromorphone administration or until patients were discharged, underwent a procedure to treat their painful condition, or received a rescue analgesic.ResultsWe enrolled 35 children. Fifteen, 11, and 9 children required a total dose of 0.03, 0.045, and 0.06 mg/kg, respectively. Patients in each dose group experienced an absolute decrease in pain score of ≥3/10 and percent reduction >40% within 5–15 min of completing dose-titration administration of hydromorphone. Duration of analgesia (i.e. time until rescue analgesic administered) >1 h was observed in 85.7% of patients. Patients not requiring rescue analgesics had mild or no pain until discharged or their painful conditions were treated. Three (8.6%) patients required a rescue analgesic <1 h after hydromorphone administration. There were no major adverse events.ConclusionsIntranasal hydromorphone led to rapid, clinically significant and frequently sustained decreases in pain intensity in children. No major adverse events were observed in this preliminary sample.Clinical Trials Registration Number: NCT02437669  相似文献   
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