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1.
Detailed contemporary knowledge of the characteristics of the surgical population, national anaesthetic workload, anaesthetic techniques and behaviours are essential to monitor productivity, inform policy and direct research themes. Every 3–4 years, the Royal College of Anaesthetists, as part of its National Audit Projects (NAP), performs a snapshot activity survey in all UK hospitals delivering anaesthesia, collecting patient-level encounter data from all cases under the care of an anaesthetist. During November 2021, as part of NAP7, anaesthetists recorded details of all cases undertaken over 4 days at their site through an online survey capturing anonymous patient characteristics and anaesthetic details. Of 416 hospital sites invited to participate, 352 (85%) completed the activity survey. From these, 24,177 reports were returned, of which 24,172 (99%) were included in the final dataset. The work patterns by day of the week, time of day and surgical specialty were similar to previous NAP activity surveys. However, in non-obstetric patients, between NAP5 (2013) and NAP7 (2021) activity surveys, the estimated median age of patients increased by 2.3 years from median (IQR) of 50.5 (28.4–69.1) to 52.8 (32.1–69.2) years. The median (IQR) BMI increased from 24.9 (21.5–29.5) to 26.7 (22.3–31.7) kg.m–2. The proportion of patients who scored as ASA physical status 1 decreased from 37% in NAP5 to 24% in NAP7. The use of total intravenous anaesthesia increased from 8% of general anaesthesia cases to 26% between NAP5 and NAP7. Some changes may reflect the impact of the COVID-19 pandemic on the anaesthetic population, though patients with confirmed COVID-19 accounted for only 149 (1%) cases. These data show a rising burden of age, obesity and comorbidity in patients requiring anaesthesia care, likely to impact UK peri-operative services significantly.  相似文献   
2.

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   
3.
Background: The use of improvizational theater (“improv”) in health professional education (“medical improv”) is an emerging field. However, optimal curricular design features and learning outcomes have not yet been systematically described.

Objective: To synthesize evidence on learning outcomes and curricular design elements of improvizational theater training in health professions education.

Methods: A literature search with keywords “Improv” and “Improvisational Theatre” was undertaken in January 2016 in Ovid MEDLINE, CINHAL, EMBASE, SCOPUS, Web of Science, and ERIC, with an accompanying gray literature search. Four authors coded and achieved consensus on themes relating to curricular design elements and learning outcomes, which were mapped onto the CanMEDS framework.

Results: Seven articles met inclusion criteria. Key curricular design features included (i) facilitators with dual clinical and theater expertise; (ii) creating a low-stakes environment; and (iii) engaging in debrief to highlight clinical relevance. Improv curricula were found to impact most CanMEDS roles, including: Medical Expert (comfort with uncertainty); Leader (team management); Scholar (feedback, self-reflection); Communicator (empathy, active listening, non-verbal communication); Collaborator (culture of trust); and Professional (resiliency and confidence). Mechanisms by which improv may promote acquisition of these professional competencies, and the utility of improv in areas such as interprofessional team development, leadership, and wellness and resiliency are discussed.  相似文献   

4.
Background: There are evidence-practice gaps in all areas of aphasia management across the continuum of care. Despite the recognition that effective implementation strategies are needed to improve the consistency of speech pathologists’ aphasia management practices, there have been few studies investigating this important issue. Therefore, little is known about the effectiveness of implementation strategies in the field of aphasiology. In light of the developing field of knowledge translation, it is important to review the aphasia implementation literature to highlight current trends, draw together findings, and determine future implementation research needs.

Aims: To critically review, summarise, and discuss the implementation literature in the field of aphasiology to date, in order to guide clinical aphasiologists to work towards closing the evidence-practice gaps in aphasia management.

Main contribution: A review of the literature in this developing area of expertise in the field of aphasiology, with examples of practical applications.

Conclusions: Only six implementation studies have been published in aphasia (related to conversation partner training, discourse analysis, information provision, and collaborative goal-setting practices), showing there is a need for capacity building in this area. Therefore, we are not yet able to state what interventions are effective in which context, nor fully understand how behaviour change occurs for clinicians providing aphasia management. Implications for speech-language pathologists are discussed. An overarching call to action is the need for clinicians and researchers to work together to drive future implementation efforts that can succeed in closing the aphasia management evidence-practice gaps.  相似文献   

5.

Background

The randomized EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial reported a similar rate of the 3-year composite primary endpoint of death, myocardial infarction (MI), or stroke in patients with left main coronary artery disease (LMCAD) and site-assessed low or intermediate SYNTAX scores treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Whether these results are consistent in high-risk patients with diabetes, who have fared relatively better with CABG in most prior trials, is unknown.

Objectives

In this pre-specified subgroup analysis from the EXCEL trial, the authors sought to examine the effect of diabetes in patients with LMCAD treated with PCI versus CABG.

Methods

Patients (N = 1,905) with LMCAD and site-assessed low or intermediate CAD complexity (SYNTAX scores ≤32) were randomized 1:1 to PCI with everolimus-eluting stents versus CABG, stratified by the presence of diabetes. The primary endpoint was the rate of a composite of all-cause death, stroke, or MI at 3 years. Outcomes were examined in patients with (n = 554) and without (n = 1,350) diabetes.

Results

The 3-year composite primary endpoint was significantly higher in diabetic compared with nondiabetic patients (20.0% vs. 12.9%; p < 0.001). The rate of the 3-year primary endpoint was similar after treatment with PCI and CABG in diabetic patients (20.7% vs. 19.3%, respectively; hazard ratio: 1.03; 95% confidence interval: 0.71 to 1.50; p = 0.87) and nondiabetic patients (12.9% vs. 12.9%, respectively; hazard ratio: 0.98; 95% confidence interval: 0.73 to 1.32; p = 0.89). All-cause death at 3 years occurred in 13.6% of PCI and 9.0% of CABG patients (p = 0.046), although no significant interaction was present between diabetes status and treatment for all-cause death (p = 0.22) or other endpoints, including the 3-year primary endpoint (p = 0.82) or the major secondary endpoints of death, MI, or stroke at 30 days (p = 0.61) or death, MI, stroke, or ischemia-driven revascularization at 3 years (p = 0.65).

Conclusions

In the EXCEL trial, the relative 30-day and 3-year outcomes of PCI with everolimus-eluting stents versus CABG were consistent in diabetic and nondiabetic patients with LMCAD and site-assessed low or intermediate SYNTAX scores.(Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization [EXCEL]; NCT01205776)  相似文献   
6.
Volunteer infection studies using the induced blood stage malaria (IBSM) model have been shown to facilitate antimalarial drug development. Such studies have traditionally been undertaken in single‐dose cohorts, as many as necessary to obtain the dose‐response relationship. To enhance ethical and logistic aspects of such studies, and to reduce the number of cohorts needed to establish the dose‐response relationship, we undertook a retrospective in silico analysis of previously accrued data to improve study design. A pharmacokinetic (PK)/pharmacodynamic (PD) model was developed from initial fictive‐cohort data for OZ439 (mixing the data of the three single‐dose cohorts as: n = 2 on 100 mg, 2 on 200 mg, and 4 on 500 mg). A three‐compartment model described OZ439 PKs. Net growth of parasites was modeled using a Gompertz function and drug‐induced parasite death using a Hill function. Parameter estimates for the PK and PD models were comparable for the multidose single‐cohort vs. the pooled analysis of all cohorts. Simulations based on the multidose single‐cohort design described the complete data from the original IBSM study. The novel design allows for the ascertainment of the PK/PD relationship early in the study, providing a basis for rational dose selection for subsequent cohorts and studies.

Study Highlights
  • WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
☑ Volunteer infection studies are routinely used in antimalarial drug development to generate early pharmacokinetic/pharmacodynamic data for compounds.
  • WHAT QUESTION DID THIS STUDY ADDRESS?
☑ Can in silico analyses be used to suggest improvements to volunteer infection study designs?
  • WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
☑ Multiple dose adaptive trial designs can potentially reduce the number of cohorts needed to establish the dose‐response relationship in volunteer infection studies.
  • HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
☑ Real time data analyses can be used to recommend doses for adaptive volunteer infection studies.

Volunteer infection studies using the induced blood stage malaria (IBSM) model have been recognized as a valuable system for defining the key pharmacokinetic (PK) and pharmacodynamic (PD) relationships for dose selection in antimalarial drug development. 1 , 2 , 3 , 4 , 5 , 6 , 7 In such studies, healthy volunteers are inoculated intravenously with a given quantity (with small variability) of Plasmodium‐infected red cells. Parasitemia is then followed by quantitative polymerase chain reaction until a prespecified treatment threshold is reached when the test drug is administered. Parasite and drug concentrations are then measured. These studies are conducted prior to phase II dose‐response (D‐R) trials and can be included in an integrated first‐in‐human study protocol, or after completion of the first‐in‐human PK and safety study. IBSM studies have been typically designed as flexible multiple cohort studies where each volunteer of one cohort receives a single dose of the same amount of drug (“single dose per cohort”). 2 , 3 , 4 , 5 After each cohort, a decision is made to stop or to add a cohort to test a lower or higher dose based on the response observed in the previous cohorts.For the multiple single‐dose‐per‐cohort design, the starting dose is typically selected based on safety and PK information from a phase I single ascending dose (SAD) study and, more recently, on preclinical data from a severe combined immunodeficient mouse model, with the dose selected on the basis of being best able to inform the D‐R relationship, rather than aiming for cure. This approach, where a single dose is tested in all subjects of the initial cohort, risks missing the dose likely to be most informative for defining the PK/PD relationship.An alternative approach is to spread a range of doses across a smaller number of subjects within the initial cohort and use PK/PD models developed based on data from this cohort to support dose selections of subsequent cohorts and studies. Using data from a previous study, 2 we undertook an in silico investigation of such an adaptive study design, aiming to reduce the number of subjects exposed to inefficacious doses, and to establish a D‐R relationship. This multiple‐dose‐groups‐per‐cohort design, referred to as the “2‐2‐4” design, is contrasted with the already implemented study design depicted in Figure  1 .Open in a separate windowFigure 1Comparison of standard and adaptive designs of IBSM studies. A/B/C, dose levels to be selected during the progress of the study based on pharmacokinetic/pharmacodynamic results of the initial cohort; CHMI, controlled human malaria infection; D‐R, dose‐response; IBSM, induced blood stage malaria infection; n, number of subjects at each dose.The objectives of this retrospective analysis were to: (i) compare PK/PD parameter estimates from the initial cohort of the 2‐2‐4 study design with the prior results from the data of the full study and (ii) propose a preliminary workflow to establish D‐R early in an IBSM study, and use modeling and simulation (M&S) to support dose selections for subsequent cohorts and later phase clinical trials.  相似文献   
7.
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   
8.

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   
9.
10.

Introduction

The aim of this study was to evaluate the root canal shaping effect of instruments manufactured from nickel titanium, M-Wire, and Gold wire with different glide path preparation techniques.

Methods

One hundred thirty-five mesiobuccal canals of extracted human maxillary molars were randomly divided into 3 equal groups (N = 45) for glide path preparation with K-files (KF) (Dentsply Sirona, Ballaigues, Switzerland), One G (OG) files (Micro-Mega, Besançon, France), and ProGlider (PG) files (Dentsply Sirona). Specimens of each glide path group were further divided equally into 3 groups for instrumentation with ProTaper Next (PTN, Dentsply Sirona), One Shape (OS, Micro-Mega), and WaveOne Gold (WOG, Dentsply Sirona) systems (n = 15). Micro–computed tomographic imaging was used to scan teeth before instrumentation and after shaping to compare centering ratio and canal transportation values at the apical, midroot, and coronal levels and the overall changes in canal volume. Data sets were statistically analyzed (analysis of variance and Kruskal-Wallis H tests).

Results

The centering ratios for all groups were statistically similar at all levels. Apical canal transportation was significantly high for K/OS and K/PTN (P = .003). Midroot canal transportation was significantly high for K/PTN, K/OS, and OG/OS (P = .0003). Coronal canal transportation was significantly high for K/PTN and K/OS (P = .011). The highest change in canal volume was observed with all PTN groups and the lowest with PG/WOG (P = .06).

Conclusions

WOG manufactured from Gold wire combined with PG showed better root canal shaping ability and removed less dentin from the canal walls. The nickel-titanium (OS) and M-Wire (PTN) instruments used in combination with KF significantly transported more canals. PTN removed the most dentin from the canal walls regardless of the GPP technique.  相似文献   
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