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1.
J Robot Surg ; 18(1): 113, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38451376

ABSTRACT

New robot-assisted surgery platforms being developed will be required to have proficiency-based simulation training available. Scoring methodologies and performance feedback for trainees are currently not consistent across all robotic simulator platforms. Also, there are virtually no prior publications on how VR simulation passing benchmarks have been established. This paper compares methods evaluated to determine the proficiency-based scoring thresholds (a.k.a. benchmarks) for the new Medtronic Hugo™ RAS robotic simulator. Nine experienced robotic surgeons from multiple disciplines performed the 49 skills exercises 5 times each. The data were analyzed in 3 different ways: (1) include all data collected, (2) exclude first sessions, (3) exclude outliers. Eliminating the first session discounts becoming familiar with the exercise. Discounting outliers allows removal of potentially erroneous data that may be due to technical issues, unexpected distractions, etc. Outliers were identified using a common statistical technique involving the interquartile range of the data. Using each method above, mean and standard deviations were calculated, and the benchmark was set at a value of 1 standard deviation above the mean. In comparison to including all the data, when outliers are excluded, fewer data points are removed than just excluding first sessions, and the metric benchmarks are made more difficult by an average of 11%. When first sessions are excluded, the metric benchmarks are made easier by an average of about 2%. In comparison with benchmarks calculated using all data points, excluding outliers resulted in the biggest change making the benchmarks more challenging. We determined that this method provided the best representation of the data. These benchmarks should be validated with future clinical training studies.


Subject(s)
Robotic Surgical Procedures , Robotics , Surgeons , Humans , Benchmarking , Robotic Surgical Procedures/methods , Computer Simulation
2.
J Am Chem Soc ; 146(5): 2944-2949, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38227776

ABSTRACT

Methods to incorporate stable radioisotopes are integral to pharmaceutical and agrochemical development. However, despite the prevalence of pyridines in candidate compounds, methods to incorporate 15N atoms within their structures are limited. Here, we present a general approach to pyridine 15N-labeling that proceeds via ring-opening to NTf-Zincke imines and then ring-closure with commercially available 15NH4Cl salts. This process functions on a range of substituted pyridines, from simple building block-type compounds to late-stage labeling of complex pharmaceuticals, and 15N-incorporation is >95% in most cases. The reactivity of the Zincke imine intermediates also enables deuteration of the pyridine C3- and C5-positions, resulting in higher mass isotopologs required for LCMS analysis of biological fluids during drug development.

3.
Clin Transl Sci ; 16(11): 2236-2252, 2023 11.
Article in English | MEDLINE | ID: mdl-37817426

ABSTRACT

This single-center study administered MIJ821 (onfasprodil) as an intravenous infusion to healthy volunteers and included two parts: a single ascending dose study (Part 1) and a repeated intravenous dose study (Part 2). Primary objective was to evaluate the safety and tolerability of single ascending intravenous doses infused over a 40-min period and of two repeated doses (1 week apart) of MIJ821 in healthy volunteers. Secondary objectives were to assess the pharmacokinetics of MIJ821 after intravenous infusion in Part 1 and Part 2 of the study. Overall, 43 subjects in Part 1 and 12 subjects in Part 2 were randomized in the study. Median age in Part 1 and Part 2 was 45.0 and 43.5 years, respectively, with the majority being Caucasian (Part 1: 84%; Part 2: 92%). 19 subjects (44.2%) in Part 1 and 8 subjects (66.7%) in Part 2 experienced at least one adverse event (AE). Following single dose in Part 1 and Part 2, the AUCinf values of MIJ821 increased in a dose-proportional manner across the dose range 0.016-0.48 mg/kg and the Cmax values in a slight overproportional manner across the dose range 0.048-0.48 mg/kg. At the highest dose of 0.48 mg/kg, the geometric mean AUCinf was 708 h ng/mL and the geometric mean Cmax was 462 ng/mL. Inspection of 1-h post-dose resting electroencephalography activity across cohorts showed a relationship to administered dose, providing exploratory evidence of distal target engagement. In conclusion, MIJ821 showed a good safety and tolerability profile in healthy volunteers. Dissociative AEs were mild, transient, and dose-dependent.


Subject(s)
Infusions, Intravenous , Humans , Double-Blind Method , Area Under Curve , Healthy Volunteers , Dose-Response Relationship, Drug
4.
Foot Ankle Spec ; 16(4): 392-398, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36181272

ABSTRACT

INTRODUCTION: Surgical treatment for insertional Achilles tendinosis (IAT) sometimes requires tendon repair augmentation. The purpose of this study is to evaluate the efficacy of polycaprolactone-based polyurethane urea (PUUR) matrix augmentation in the treatment of IAT. METHODS: A retrospective review was performed in surgically treated IAT. Repairs were augmented with a PUUR matrix. Factors evaluated included date of full weightbearing, patient satisfaction, Visual Analog Scale (VAS) pain score, strength, and ankle motion. The Wilcoxon signed-rank test was used to compare baseline and final follow-up VAS scores. RESULTS: A total of 18 cases were included in the study. The mean patient age was 54.61 ± 8.25 (40-75) years with a mean follow-up of 163.61 ± 57.81 (92-314) days. Patient satisfaction was obtained on 15 of 18 patients, with 14 patients satisfied with their outcome. Mean VAS for pain significantly decreased from 6.19 ± 1.97 (2.5-9) to 0.83 ± 1.54 (0-5) postoperatively, which was statistically significant (P < .01). CONCLUSION: Achilles tendon augmentation with the PUUR matrix is a viable option in the treatment of IAT. Its use in this condition has minimal morbidity and can be an alternative to other forms of augmentation. LEVELS OF EVIDENCE: Level IV: Retrospective case series.


Subject(s)
Achilles Tendon , Tendinopathy , Humans , Middle Aged , Achilles Tendon/surgery , Retrospective Studies , Polyurethanes , Tendinopathy/surgery , Pain , Urea , Treatment Outcome
5.
Science ; 378(6621): 773-779, 2022 11 18.
Article in English | MEDLINE | ID: mdl-36395214

ABSTRACT

Pyridine halogenation reactions are crucial for obtaining the vast array of derivatives required for drug and agrochemical development. However, despite more than a century of synthetic endeavors, halogenation processes that selectively functionalize the carbon-hydrogen bond in the 3-position of a broad range of pyridine precursors remain largely elusive. We report a reaction sequence of pyridyl ring opening, halogenation, and ring closing whereby the acyclic Zincke imine intermediates undergo highly regioselective halogenation reactions under mild conditions. Experimental and computational mechanistic studies indicate that the nature of the halogen electrophile can modify the selectivity-determining step. Using this method, we produced a diverse set of 3-halopyridines and demonstrated late-stage halogenation of complex pharmaceuticals and agrochemicals.

6.
Surgery ; 172(6): 1656-1664, 2022 12.
Article in English | MEDLINE | ID: mdl-36123174

ABSTRACT

BACKGROUND: Due to a shortage and maldistribution of surgeons within Kenya, doctors with limited formal surgical training often perform emergency surgical procedures such as appendectomy. This lack of training can compromise patient outcomes and complicate care delivery. Our aim was to develop a low-cost simulator and skills curriculum to effectively teach open appendectomy. METHODS: Surgeons from 4 countries participated in semi-structured interviews to define the steps and technique of open appendectomy using cognitive task analysis. Using this input, our Academic Model Providing Access to Healthcare surgical team developed a curriculum, including a simulator and feedback mechanism. Surgeons and surgical trainees from Kenya and the United States tested the simulator prototype and provided feedback for its refinement based on clarity, utility, and realism. RESULTS: Instructions for a self-constructed simulator were developed at the cost of 70 Kenyan shillings (0.64 US dollars). Fifteen surgeons and surgical residents gave feedback on the simulator and curriculum, and each was presented with an updated version based on feedback. Overall, the curriculum was clear, with each sub-step receiving a median score of ≥83.5 out of 100 for clarity; however, through iterative design, the utility of sub-steps on the simulator improved. CONCLUSION: A comprehensive open appendectomy curriculum, including a low-cost appendectomy simulator model, was developed and refined using surgeon feedback. Such curricula may benefit trainees in low-resource settings who may otherwise have limited access to quality training material.


Subject(s)
Laparoscopy , Mobile Applications , Humans , Appendectomy , Kenya , Laparoscopy/education , Curriculum , Clinical Competence
7.
J Am Coll Surg ; 234(6): 1181-1192, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35703817

ABSTRACT

BACKGROUND: Artificial intelligence (AI) methods and AI-enabled metrics hold tremendous potential to advance surgical education. Our objective was to generate consensus guidance on specific needs for AI methods and AI-enabled metrics for surgical education. STUDY DESIGN: The study included a systematic literature search, a virtual conference, and a 3-round Delphi survey of 40 representative multidisciplinary stakeholders with domain expertise selected through purposeful sampling. The accelerated Delphi process was completed within 10 days. The survey covered overall utility, anticipated future (10-year time horizon), and applications for surgical training, assessment, and feedback. Consensus was agreement among 80% or more respondents. We coded survey questions into 11 themes and descriptively analyzed the responses. RESULTS: The respondents included surgeons (40%), engineers (15%), affiliates of industry (27.5%), professional societies (7.5%), regulatory agencies (7.5%), and a lawyer (2.5%). The survey included 155 questions; consensus was achieved on 136 (87.7%). The panel listed 6 deliverables each for AI-enhanced learning curve analytics and surgical skill assessment. For feedback, the panel identified 10 priority deliverables spanning 2-year (n = 2), 5-year (n = 4), and 10-year (n = 4) timeframes. Within 2 years, the panel expects development of methods to recognize anatomy in images of the surgical field and to provide surgeons with performance feedback immediately after an operation. The panel also identified 5 essential that should be included in operative performance reports for surgeons. CONCLUSIONS: The Delphi panel consensus provides a specific, bold, and forward-looking roadmap for AI methods and AI-enabled metrics for surgical education.


Subject(s)
Artificial Intelligence , Benchmarking , Consensus , Humans , Surveys and Questionnaires
8.
Geospat Health ; 17(1)2022 05 06.
Article in English | MEDLINE | ID: mdl-35532018

ABSTRACT

Maternal address information captured on birth records is increasingly used to estimate residential environmental exposures during pregnancy. However, there has been limited assessment of the geocoding precision of birth records, particularly since the adoption of the 2003 standard birth certificate in 2015. To address this gap, this study evaluated the geocoding precision of live and stillbirth records of Kentucky residents over ten years, from 2008 through 2017. This study summarized the demographic characteristics of imprecisely geocoded records and, using a bivariate logistic regression, identified covariates associated with poor geocoding precision among three population density designations-metro, non-metro, and rural. We found that in metro areas, after adjusting for area deprivation, education, and the race, age and education of both parents, records for Black mothers had 48% lower odds of imprecise geocoding (aOR=0.52, 95% CI: 0.48, 0.56), while Black women in rural areas had 96% higher odds of imprecise geocoding (aOr=1.96, 95% CI: 1.68, 2.28). This study also found that over the study period, rural and non-metro areas began with a high proportion of imprecisely geocoded records (38% in rural areas, 19% in non-metro), but both experienced an 8% decline in imprecisely geocoded records over the study period (aOr=0.92, 95% CI: 0.92, 0.94). This study shows that, while geocoding precision has improved in Kentucky, further work is needed to improve geocoding in rural areas and address racial and ethnic disparities.


Subject(s)
Birth Certificates , Geographic Mapping , Environmental Exposure , Female , Humans , Kentucky/epidemiology , Pregnancy , Rural Population
9.
Ann Surg ; 276(1): 88-93, 2022 07 01.
Article in English | MEDLINE | ID: mdl-33214434

ABSTRACT

OBJECTIVE: To define criteria for robotic credentialing using expert consensus. BACKGROUND: A recent review of institutional robotic credentialing policies identified significant variability and determined current policies are largely inadequate to ensure surgeon proficiency and may threaten patient safety. METHODS: Twenty-eight national robotic surgery experts were invited to participate in a consensus conference. After review of available institutional policies and discussion, the group developed a 91 proposed criteria. Using a modified Delphi process the experts were asked to indicate their agreement with the proposed criteria in three electronic survey rounds after the conference. Criteria that achieved 80% or more in agreement (consensus) in all rounds were included in the final list. RESULTS: All experts agreed that there is a need for standardized robotic surgery credentialing criteria across institutions that promote surgeon proficiency. Forty-nine items reached consensus in the first round, 19 in the second, and 8 in the third for a total of 76 final items. Experts agreed that privileges should be granted based on video review of surgical performance and attainment of clearly defined objective proficiency benchmarks. Parameters for ongoing outcome monitoring were determined and recommendations for technical skills training, proctoring, and performance assessment were defined. CONCLUSIONS: Using a systematic approach, detailed credentialing criteria for robotic surgery were defined. implementation of these criteria uniformly across institutions will promote proficiency of robotic surgeons and has the potential to positively impact patient outcomes.


Subject(s)
Robotic Surgical Procedures , Robotics , Surgeons , Clinical Competence , Consensus , Credentialing , Delphi Technique , Humans , Robotic Surgical Procedures/education
10.
J Thorac Dis ; 13(10): 6116-6122, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34795962

ABSTRACT

A great technological revolution in surgery occurred with the introduction of laparoscopic and other minimally invasive procedures, with enormous patient benefits. Robotic-assisted surgery (RAS) is a form of minimally invasive surgery that overcomes some of the limitations of laparoscopic techniques. Until recently, there were few standardized curricula for RAS. The Fundamentals of Robotic (FRS) developed a process through expert consensus conferences to develop an effective and validated curriculum for basic robotic surgery. A specialty specific curriculum for thoracic robotic surgery is also needed. The Fundamentals of Thoracic Robotic Surgery (FTRS) Consensus Conference brought together expert thoracic surgeons to build upon the accomplishments of FRS and incorporate the experiences of thoracic societies and academic institutions to establish a standardized FTRS curriculum for the development and maintenance of specialty-specific robotic surgical skills. A task deconstruction was completed for the thoracic 'signature' procedure, the lobectomy and training items and potential errors were identified for each step of the procedure. A final outline of the FTRS curriculum was developed during the conference and physical and virtual reality thoracic surgery training models were discussed. Following the conference, the steering committee completed the FTRS curriculum with editorial review from all stakeholders. The FTRS consensus conference followed the validated FRS model but in an accelerated process due to important groundwork set by experts in the FRS consensus conferences. A full online curriculum and supporting psychomotor skills training and team communication has been developed for the lobectomy procedure.

11.
Nature ; 594(7862): 217-222, 2021 06.
Article in English | MEDLINE | ID: mdl-33910228

ABSTRACT

Fluoroalkyl groups profoundly affect the physical properties of pharmaceuticals and influence almost all metrics associated with their pharmacokinetic and pharmacodynamic profile1-4. Drug candidates increasingly contain trifluoromethyl (CF3) and difluoromethyl (CF2H) groups, and the same trend in agrochemical development shows that the effect of fluoroalkylation translates across human, insect and plant life5,6. New fluoroalkylation reactions have undoubtedly stimulated this shift; however, methods that directly convert C-H bonds into C-CF2X groups (where X is F or H) in complex drug-like molecules are rare7-13. Pyridines are the most common aromatic heterocycles in pharmaceuticals14, but only one approach-via fluoroalkyl radicals-is viable for achieving pyridyl C-H fluoroalkylation in the elaborate structures encountered during drug development15-17. Here we develop a set of bench-stable fluoroalkylphosphines that directly convert the C-H bonds in pyridine building blocks, drug-like fragments and pharmaceuticals into fluoroalkyl derivatives. No preinstalled functional groups or directing groups are required. The reaction tolerates a variety of sterically and electronically distinct pyridines, and is exclusively selective for the 4-position in most cases. The reaction proceeds through initial formation of phosphonium salts followed by sp2-sp3 coupling of phosphorus ligands-an underdeveloped manifold for forming C-C bonds.


Subject(s)
Carbon/chemistry , Fluorine/chemistry , Hydrogen/chemistry , Phosphorus/chemistry , Pyridines/chemistry , Alkylation , Animals , Humans , Ligands , Pharmaceutical Preparations/chemistry , Pharmacokinetics , Phosphines/chemistry
12.
J Robot Surg ; 15(2): 187-193, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32409995

ABSTRACT

Fundamentals of robotic surgery (FRS) is a proficiency-based progression curriculum developed by robotic surgery experts from multiple specialty areas to address gaps in existing robotic surgery training curricula. The RobotiX Mentor is a virtual reality training platform for robotic surgery. Our aims were to determine if robotic surgery novices would demonstrate improved technical skills after completing FRS training on the RobotiX Mentor, and to compare the effectiveness of FRS across training platforms. An observational, pre-post design, multi-institutional rater-blinded trial was conducted at two American College of Surgeons Accredited Education Institutes-certified simulation centers. Robotic surgery novices (n = 20) were enrolled and trained to expert-derived benchmarks using FRS on the RobotiX Mentor. Participants' baseline skill was assessed before (pre-test) and after (post-test) training on an avian tissue model. Tests were video recorded and graded by blinded raters using the Global Evaluative Assessment of Robotic Skills (GEARS) and a 32-criteria psychomotor checklist. Post hoc comparisons were conducted against previously published comparator groups. On paired-samples T tests, participants demonstrated improved performance across all GEARS domains (p < 0.001 to p = 0.01) and for time (p < 0.001) and errors (p = 0.003) as measured by psychometric checklist. By ANOVA, improvement in novices' skill after FRS training on the RobotiX Mentor was not inferior to improvement reported after FRS training on previously published platforms. Completion of FRS on the RobotiX Mentor resulted in improved robotic surgery skills among novices, proving effectiveness of training. These data provide additional validity evidence for FRS and support use of the RobotiX Mentor for robotic surgery skill acquisition.


Subject(s)
Clinical Competence , Curriculum , Education, Medical/methods , Robotic Surgical Procedures/education , Simulation Training/methods , Virtual Reality , Humans
13.
Surg Endosc ; 35(5): 2104-2109, 2021 05.
Article in English | MEDLINE | ID: mdl-32377839

ABSTRACT

BACKGROUND: Robotic surgery has seen unprecedented growth, requiring hospitals to establish or update credentialing policies regarding this technology. Concerns about verification of robotic surgeon proficiency and the adequacy of current credentialing criteria to maintain patient safety have arisen. The aim of this project was to examine existing institutional credentialing requirements for robotic surgery and evaluate their adequacy in ensuring surgeon proficiency. METHODS: Robotic credentialing policies for community and academic surgery programs were acquired and reviewed. Common criteria across institutions related to credentialing and recredentialing were identified and the average, standard deviation, and range of numeric requirements, if defined, was calculated. Criteria for proctors and assistants were also analyzed. RESULTS: Policies from 42 geographically dispersed US hospitals were reviewed. The majority of policies relied on a defined number of proctored cases as a surrogate for proficiency with an average of 3.24 ± 1.69 and a range of 1-10 cases required for initial credentialing. While 34 policies (81%) addressed maintenance of privileges requirements, there was wide variability in the average number of required robotic cases (7.19 ± 3.28 per year) and range (1-15 cases per year). Only 11 policies (26%) addressed the maximum allowable time gap between robotic cases. CONCLUSION: Significant variability in credentialing policies exists in a representative sample of US hospitals. Most policies require completion of a robotic surgery training course and a small number of proctored cases; however, ongoing objective performance assessments and patient outcome monitoring was rarely described. Existing credentialing policies are likely inadequate to ensure surgeon proficiency; therefore, development and wide implementation of robust credentialing guidelines is recommended to optimize patient safety and outcomes.


Subject(s)
Credentialing , Robotic Surgical Procedures/education , Clinical Competence , Credentialing/standards , Hospitals , Humans , Organizational Policy , Robotic Surgical Procedures/standards , Surgeons , United States
15.
Ann Surg ; 272(2): 384-392, 2020 08.
Article in English | MEDLINE | ID: mdl-32675553

ABSTRACT

OBJECTIVE: To demonstrate the noninferiority of the fundamentals of robotic surgery (FRS) skills curriculum over current training paradigms and identify an ideal training platform. SUMMARY BACKGROUND DATA: There is currently no validated, uniformly accepted curriculum for training in robotic surgery skills. METHODS: Single-blinded parallel-group randomized trial at 12 international American College of Surgeons (ACS) Accredited Education Institutes (AEI). Thirty-three robotic surgery experts and 123 inexperienced surgical trainees were enrolled between April 2015 and November 2016. Benchmarks (proficiency levels) on the 7 FRS Dome tasks were established based on expert performance. Participants were then randomly assigned to 4 training groups: Dome (n = 29), dV-Trainer (n = 30), and DVSS (n = 32) that trained to benchmarks and control (n = 32) that trained using locally available robotic skills curricula. The primary outcome was participant performance after training based on task errors and duration on 5 basic robotic tasks (knot tying, continuous suturing, cutting, dissection, and vessel coagulation) using an avian tissue model (transfer-test). Secondary outcomes included cognitive test scores, GEARS ratings, and robot familiarity checklist scores. RESULTS: All groups demonstrated significant performance improvement after skills training (P < 0.01). Participating residents and fellows performed tasks faster (DOME and DVSS groups) and with fewer errors than controls (DOME group; P < 0.01). Inter-rater reliability was high for the checklist scores (0.82-0.97) but moderate for GEARS ratings (0.40-0.67). CONCLUSIONS: We provide evidence of effectiveness for the FRS curriculum by demonstrating better performance of those trained following FRS compared with controls on a transfer test. We therefore argue for its implementation across training programs before surgeons apply these skills clinically.


Subject(s)
Clinical Competence , Computer Simulation , Robotic Surgical Procedures/education , Simulation Training/methods , Specialties, Surgical/education , Analysis of Variance , Curriculum , Female , Humans , Male , Risk Assessment , Single-Blind Method , Treatment Outcome
16.
Adv Ther ; 37(7): 3370-3391, 2020 07.
Article in English | MEDLINE | ID: mdl-32524499

ABSTRACT

INTRODUCTION: PF-06881894 is a proposed biosimilar to pegfilgrastim (Neulasta®). This study evaluated the pharmacodynamic/pharmacokinetic (PD/PK) equivalence, immunogenicity, and safety of PF-06881894 vs pegfilgrastim reference products (US- and EU-Neulasta®) in healthy volunteers. METHODS: A phase 1, open-label, randomized, crossover study was conducted to assess the pharmacologic equivalence and safety of a single 6-mg dose of PF-06881894, pegfilgrastim-US, and pegfilgrastim-EU. The primary PD endpoints were area under the effect-versus-time curve for absolute neutrophil count (ANC) from dose administration to 288 h postdose, and maximum observed ANC value among subjects confirmed negative for anti-pegfilgrastim antibodies. Primary PK variables included area under the serum pegfilgrastim-versus-time curve from the time of dose administration to time infinity and maximum observed serum pegfilgrastim concentration. A second phase 1, open-label, randomized (1:1), parallel-group, non-inferiority study was conducted to assess the immunogenicity and safety of multiple 6-mg doses of PF-06881894 versus pegfilgrastim-US. The primary endpoint for the immunogenicity study was the proportion of subjects with both negative baseline and confirmed positive postdose anti-pegfilgrastim antibodies at any time during the study. RESULTS: Across the single- and multiple-dose studies (N = 153 and N = 420 treated subjects, respectively), demographics for age (18-65 years), male gender (n = 264/573), and white race (n = 423/573) were similar. Three-way PD/PK equivalence of PF-06881894, pegfilgrastim-US, and pegfilgrastim-EU was demonstrated with the primary PD endpoints and primary PK variables being completely contained within the predefined 90% confidence interval acceptance limits (80-125%). The non-inferiority of PF-06881894 versus pegfilgrastim-US in terms of immunogenicity was established according to the prespecified non-inferiority margin (≤10%). Overall, there were no clinically meaningful differences in safety profiles among or between study groups. CONCLUSIONS: Single-dose PF-06881894 demonstrated PD/PK equivalence and comparable safety with US- and EU-pegfilgrastim reference products. Multiple-dose PF-06881894 demonstrated immunogenicity non-inferiority to pegfilgrastim-US with comparable safety. Both studies contributed to the totality of evidence supporting biosimilarity. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02629289; NCT03273842 (C1221005).


Subject(s)
Asian People/statistics & numerical data , Biosimilar Pharmaceuticals/pharmacology , Filgrastim/pharmacology , Healthy Volunteers/statistics & numerical data , Neutrophils/drug effects , Polyethylene Glycols/pharmacology , Therapeutic Equivalency , Adolescent , Adult , Cross-Over Studies , Double-Blind Method , Female , Humans , Male , Young Adult
17.
J Am Chem Soc ; 142(25): 11295-11305, 2020 06 24.
Article in English | MEDLINE | ID: mdl-32469220

ABSTRACT

Halopyridines are key building blocks for synthesizing pharmaceuticals, agrochemicals, and ligands for metal complexes, but strategies to selectively halogenate pyridine C-H precursors are lacking. We designed a set of heterocyclic phosphines that are installed at the 4-position of pyridines as phosphonium salts and then displaced with halide nucleophiles. A broad range of unactivated pyridines can be halogenated, and the method is viable for late-stage halogenation of complex pharmaceuticals. Computational studies indicate that C-halogen bond formation occurs via an SNAr pathway, and phosphine elimination is the rate-determining step. Steric interactions during C-P bond cleavage account for differences in reactivity between 2- and 3-substituted pyridines.


Subject(s)
Halogenation , Indicators and Reagents/chemistry , Onium Compounds/chemistry , Phosphines/chemistry , Pyridines/chemistry , Bromides/chemistry , Density Functional Theory , Indicators and Reagents/chemical synthesis , Iodides/chemistry , Lithium Chloride/chemistry , Lithium Compounds/chemistry , Models, Chemical , Onium Compounds/chemical synthesis , Phosphines/chemical synthesis
18.
Eur Urol Open Sci ; 22: 23-33, 2020 Dec.
Article in English | MEDLINE | ID: mdl-34337475

ABSTRACT

CONTEXT: The role of robot-assisted surgery continues to expand at a time when trainers and proctors have travel restrictions during the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To provide guidance on setting up and running an optimised telementoring service that can be integrated into current validated curricula. We define a standardised approach to training candidates in skill acquisition via telepresence technologies. We aim to describe an approach based on the current evidence and available technologies, and define the key elements within optimised telepresence services, by seeking consensus from an expert committee comprising key opinion leaders in training. EVIDENCE ACQUISITION: This project was carried out in phases: a systematic review of the current literature, a teleconference meeting, and then an initial survey were conducted based on the current evidence and expert opinion, and sent to the committee. Twenty-four experts in training, including clinicians, academics, and industry, contributed to the Delphi process. An accelerated Delphi process underwent three rounds and was completed within 72 h. Additions to the second- and third-round surveys were formulated based on the answers and comments from the previous rounds. Consensus opinion was defined as ≥80% agreement. EVIDENCE SYNTHESIS: There was 100% consensus regarding an urgent need for international agreement on guidance for optimised telepresence. Consensus was reached in multiple areas, including (1) infrastructure and functionality; (2) definitions and terminology; (3) protocols for training, communication, and safety issues; and (4) accountability including ethical and legal issues. The resulting formulated guidance showed good internal consistency among experts, with a Cronbach alpha of 0.90. CONCLUSIONS: Using the Delphi methodology, we achieved international consensus among experts for development and content validation of optimised telepresence services for robotic surgery training. This guidance lays the foundation for launching telepresence services in robotic surgery. This guidance will require further validation. PATIENT SUMMARY: Owing to travel restrictions during the coronavirus disease 2019 (COVID-19) pandemic, development of remote training and support via telemedicine is becoming increasingly important. We report a key opinion leader consensus view on a standardised approach to telepresence.

19.
Ann Surg Open ; 1(2): e011, 2020 Dec.
Article in English | MEDLINE | ID: mdl-37637444

ABSTRACT

Operative video has great potential to enable instant replays of critical surgical decisions for training and quality review. Recently, artificial intelligence (AI) has shown early promise as a method of enabling efficient video review, analysis, and segmentation. Despite the progress with AI analysis of surgical videos, more work needs to be done to improve the accuracy and efficiency of AI-driven video analysis. At a recent consensus conference held on July 10-11, 2020, 8 research teams shared their work using AI for surgical video analysis. Four of the teams showcased the utility of wearable technology in providing objective surgical metrics. Data from these technologies were shown to pinpoint important cognitive and motor actions during operative tasks and procedures. The results support the utility of wearable technology to facilitate efficient and accurate video analysis and segmentation.

20.
Cent Eur J Public Health ; 27(2): 115-126, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31241286

ABSTRACT

OBJECTIVE: While some countries of the WHO European Region are global leaders in tobacco control, the Newly Independent States (NIS) have the highest tobacco-smoking prevalence globally and a relatively low overall level of the WHO Framework Convention on Tobacco Control (WHO FCTC) implementation. An abridged version of the SimSmoke tobacco control policy simulation model has been developed to project the health impact of implementing tobacco-control policies in line with the WHO FCTC. METHODS: Data on population size, smoking prevalence, policy-specific effect sizes and formulas were applied in 11 NIS - Armenia, Azerbaijan, Belarus, Georgia, Kazakhstan, Kyrgyzstan, the Russian Federation, Tajikistan, Turkmenistan, Ukraine, and Uzbekistan. The aim was to project the relative reduction in smoking prevalence, number of smokers and number of smoking-attributable deaths resulting from implementing six individual and/or combined WHO FCTC measures. RESULTS: An increase in excise cigarette taxes to 75% of price yields the largest relative reduction in smoking prevalence (range 12.1-44%) for all countries. The projections show that when all six tobacco control measures are fully implemented in line with the WHO FCTC, smoking prevalence in each of the NIS countries can be reduced by at least 39% by the year 2033 (baseline 2015). CONCLUSION: The projections show that the NIS countries can expect a large number of smoking-attributable deaths just among those smokers alive today, but large reductions in smoking prevalence and smoking-attributable deaths can be achieved if the WHO FCTC demand reduction policies are implemented. The results can be used as an advocacy tool for accelerating enforcement of tobacco control laws in NIS.


Subject(s)
Health Policy , Smoking Cessation/statistics & numerical data , Smoking Prevention/legislation & jurisprudence , Smoking/epidemiology , Smoking/legislation & jurisprudence , Tobacco Use/legislation & jurisprudence , Commerce , Humans , Prevalence , Republic of Belarus/epidemiology , Russia/epidemiology , Taxes/legislation & jurisprudence , Ukraine/epidemiology
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