Resident Exposure and Involvement in Core Procedural Competencies within Pediatric Plastic Surgery.

Introduction: The implementation of competency-based residency training in plastic surgery is underway. Key competencies in plastic surgery have been previously identified, however, within the domain of pediatrics, data suggest limited exposure throughout training for Canadian graduates. This study aims to identify the exposure and involvement of residents in core pediatric cases. Methods: We performed a retrospective, multicenter review of plastic surgery resident case logs (T-Res, POWER, New Innovations) across 10 Canadian, English-speaking training programs between 2004 and 2014. Case logs were coded according to the 8 core pediatric competencies previously identified by a modified Delphi technique. Results: A total of 3061 of 59 405 cases (5.2%) logged by 55 graduating residents were core pediatric procedures with an average of 55.6 ± 23.0 cases logged per resident. The top 3 most commonly logged procedures were cleft lip repair, cleft palate repair, and setback otoplasty. The number of cases per program varied widely with the most at 731 and least at 85 logged cases. Roles across procedures have wide variation and residents are most commonly identified as the assistant rather than surgeon or co-surgeon. Conclusion: These findings highlight variability both within and across residency programs with a paucity of exposure and involvement in pediatric plastic surgery cases. This may present a conflict between current recommendations for residency-specific procedural competencies and true clinical exposure. Further curriculum development and simulation may be of benefit.

Introduction: La formation des résidents fondée sur les compétences est en voie d'être adoptée en chirurgie plastique. Les compétences clés sont d'ailleurs déjà établies, mais dans le domaine de la pédiatrie, les données indiquent que les diplômés canadiens y sont peu exposés pendant leur formation. La présente étude vise à déterminer l'exposition et la participation des résidents aux cas fondamentaux en pédiatrie. Méthodologie: Les chercheurs ont procédé à une analyse multicentrique rétrospective des registres de cas des résidents en chirurgie plastique (T-Res, POWER, New Innovations) de dix programmes de formation anglophones canadiens entre 2004 et 2014. Ils ont codé ces registres en fonction des huit compétences pédiatriques fondamentales préalablement déterminées par une technique Delphi modifiée. Résultats: Au total, 3 061 des 59 405 cas enregistrés (5,2 %) par 55 résidents de dernière année étaient des interventions pédiatriques fondamentales, et chaque résident a enregistré une moyenne de 55,6 ± 23,0 cas. Les trois interventions les plus enregistrées étaient la réparation de la fissure labiale, la réparation de la fissure palatine et l'otoplastie. Le nombre de cas enregistrés variait énormément d'un programme à l'autre, le plus élevé étant de 731 et le plus bas, de 85. Les rôles au cours des interventions étaient très variables, et les résidents étaient davantage qualifiés d'assistants que de chirurgiens ou de cochirurgiens. Conclusion: Ces observations font ressortir la variabilité des pratiques à la fois au sein des programmes de résidence et entre eux et démontrent le peu d'exposition et de participation des résidents aux cas de chirurgie plastique pédiatrique. Elles peuvent révéler un conflit entre les recommandations actuelles en matière de compétences interventionnelles des résidents et la véritable exposition clinique. Il pourrait être utile de voir à l'élaboration plus poussée du programme et des simulations.

Cox model inference for relative hazard and pure risk from stratified weight-calibrated case-cohort data.

The case-cohort design obtains complete covariate data only on cases and on a random sample (the subcohort) of the entire cohort. Subsequent publications described the use of stratification and weight calibration to increase efficiency of estimates of Cox model log-relative hazards, and there has been some work estimating pure risk. Yet there are few examples of these options in the medical literature, and we could not find programs currently online to analyze these various options. We therefore present a unified approach and R software to facilitate such analyses. We used influence functions adapted to the various design and analysis options together with variance calculations that take the two-phase sampling into account. This work clarifies when the widely used "robust" variance estimate of Barlow (Biometrics 50:1064-1072, 1994) is appropriate. The corresponding R software, CaseCohortCoxSurvival, facilitates analysis with and without stratification and/or weight calibration, for subcohort sampling with or without replacement. We also allow for phase-two data to be missing at random for stratified designs. We provide inference not only for log-relative hazards in the Cox model, but also for cumulative baseline hazards and covariate-specific pure risks. We hope these calculations and software will promote wider use of more efficient and principled design and analysis options for case-cohort studies.

Predicting absolute risk for a person with missing risk factors.

We compared methods to project absolute risk, the probability of experiencing the outcome of interest in a given projection interval accommodating competing risks, for a person from the target population with missing predictors. Without missing data, a perfectly calibrated model gives unbiased absolute risk estimates in a new target population, even if the predictor distribution differs from the training data. However, if predictors are missing in target population members, a reference dataset with complete data is needed to impute them and to estimate absolute risk, conditional only on the observed predictors. If the predictor distributions of the reference data and the target population differ, this approach yields biased estimates. We compared the bias and mean squared error of absolute risk predictions for seven methods that assume predictors are missing at random (MAR). Some methods imputed individual missing predictors, others imputed linear predictor combinations (risk scores). Simulations were based on real breast cancer predictor distributions and outcome data. We also analyzed a real breast cancer dataset. The largest bias for all methods resulted from different predictor distributions of the reference and target populations. No method was unbiased in this situation. Surprisingly, violating the MAR assumption did not induce severe biases. Most multiple imputation methods performed similarly and were less biased (but more variable) than a method that used a single expected risk score. Our work shows the importance of selecting predictor reference datasets similar to the target population to reduce bias of absolute risk predictions with missing risk factors.

Modelling the economic constraints and consequences of anaesthesia associate expansion in the UK National Health Service: a narrative review.

Shortages in the physician anaesthesia workforce have led to proposals to introduce new staff groups, notably in the UK National Health Service (NHS) Anaesthesia Associates (AAs) who have shorter training periods than doctors and could potentially contribute to workflow efficiencies in several ways. We analysed the economic viability of the most efficient staffing model, previously endorsed by both the UK Royal College of Anaesthetists and the Association of Anaesthetists, wherein one physician supervises two AAs across two operating lists (1:2 model). For this model to be economically rational (something which neither national organisation considered), the employment cost of the two AAs should be equal to or less than that of a single supervisor physician (i.e. AAs should be paid <50% of the supervisor's salary). As the supervisor can be an autonomous specialty and specialist (SAS) doctor, this sets the economically viable AA salary envelope at less than £40,000 per year. However, we report that actual advertised AA salaries greatly exceed this, with even student AAs paid up to £48,472. Economically, one way to justify such salaries is for AAs to become autonomous such that they eventually replace SAS doctors at a lower cost. We discuss some other options that might increase AA productivity to justify these salaries (e.g. ≥1:3 staffing ratios), but the medico-political consequences of each of them are also profound. Alternatively, the AA programme should be terminated as economically nonviable. These results have implications for any country seeking to introduce new models of working in anaesthesia.

Discovery of a Cushing's syndrome protein kinase A mutant that biases signaling through type I AKAPs.

Adrenal Cushing's syndrome is a disease of cortisol hypersecretion often caused by mutations in protein kinase A catalytic subunit (PKAc). Using a personalized medicine screening platform, we discovered a Cushing's driver mutation, PKAc-W196G, in ~20% of patient samples analyzed. Proximity proteomics and photokinetic imaging reveal that PKAcW196G is unexpectedly distinct from other described Cushing's variants, exhibiting retained association with type I regulatory subunits (RI) and their corresponding A kinase anchoring proteins (AKAPs). Molecular dynamics simulations predict that substitution of tryptophan-196 with glycine creates a 653-cubic angstrom cleft between the catalytic core of PKAcW196G and type II regulatory subunits (RII), but only a 395-cubic angstrom cleft with RI. Endocrine measurements show that overexpression of RIα or redistribution of PKAcW196G via AKAP recruitment counteracts stress hormone overproduction. We conclude that a W196G mutation in the kinase catalytic core skews R subunit selectivity and biases AKAP association to drive Cushing's syndrome.

Multisensory gamma stimulation promotes glymphatic clearance of amyloid.

The glymphatic movement of fluid through the brain removes metabolic waste1-4. Noninvasive 40 Hz stimulation promotes 40 Hz neural activity in multiple brain regions and attenuates pathology in mouse models of Alzheimer's disease5-8. Here we show that multisensory gamma stimulation promotes the influx of cerebrospinal fluid and the efflux of interstitial fluid in the cortex of the 5XFAD mouse model of Alzheimer's disease. Influx of cerebrospinal fluid was associated with increased aquaporin-4 polarization along astrocytic endfeet and dilated meningeal lymphatic vessels. Inhibiting glymphatic clearance abolished the removal of amyloid by multisensory 40 Hz stimulation. Using chemogenetic manipulation and a genetically encoded sensor for neuropeptide signalling, we found that vasoactive intestinal peptide interneurons facilitate glymphatic clearance by regulating arterial pulsatility. Our findings establish novel mechanisms that recruit the glymphatic system to remove brain amyloid.

Recruitment of BAG2 to DNAJ-PKAc scaffolds promotes cell survival and resistance to drug-induced apoptosis in fibrolamellar carcinoma.

The DNAJ-PKAc fusion kinase is a defining feature of fibrolamellar carcinoma (FLC). FLC tumors are notoriously resistant to standard chemotherapies, with aberrant kinase activity assumed to be a contributing factor. By combining proximity proteomics, biochemical analyses, and live-cell photoactivation microscopy, we demonstrate that DNAJ-PKAc is not constrained by A-kinase anchoring proteins. Consequently, the fusion kinase phosphorylates a unique array of substrates, including proteins involved in translation and the anti-apoptotic factor Bcl-2-associated athanogene 2 (BAG2), a co-chaperone recruited to the fusion kinase through association with Hsp70. Tissue samples from patients with FLC exhibit increased levels of BAG2 in primary and metastatic tumors. Furthermore, drug studies implicate the DNAJ-PKAc/Hsp70/BAG2 axis in potentiating chemotherapeutic resistance. We find that the Bcl-2 inhibitor navitoclax enhances sensitivity to etoposide-induced apoptosis in cells expressing DNAJ-PKAc. Thus, our work indicates BAG2 as a marker for advanced FLC and a chemotherapeutic resistance factor in DNAJ-PKAc signaling scaffolds.

Has the HCV cascade of care changed among people who inject drugs in England since the introduction of direct-acting antivirals?

BACKGROUND: In England, over 80 % of those with hepatitis C virus (HCV) infection have injected drugs. We quantified the HCV cascade of care (CoC) among people who inject drugs (PWID) in England and determined whether this improved after direct-acting antivirals (DAAs) were introduced. METHODS: We analysed data from nine rounds of national annual cross-sectional surveys of PWID recruited from drug services (2011-2019; N = 12,320). Study rounds were grouped as: 'Pre-DAAs' (2011-2014), 'Prioritised DAAs' (2015-2016) and 'Unrestricted DAAs' (2017-2019). Participants were anonymously tested for HCV antibodies and RNA and completed a short survey. We assessed the proportion of PWID recently (current/previous year) tested for HCV. For participants ever HCV treatment eligible (past chronic infection with history of treatment or current chronic infection), we assessed the CoC as: HCV testing (ever), received a positive test result, seen a specialist nurse/doctor, and ever treated. We used logistic regression to determine if individuals progressed through the CoC differently depending on time-period, whether time-period was associated with recent testing (all participants) and lifetime HCV treatment (ever eligible participants), and predictors of HCV testing and treatment in the Unrestricted DAAs period. RESULTS: The proportion of ever HCV treatment eligible PWID reporting lifetime HCV treatment increased from 12.5 % in the Pre-DAAs period to 25.6 % in the Unrestricted DAAs period (aOR:2.40, 95 %CI:1.95-2.96). There were also increases in seeing a specialist nurse/doctor. The largest loss in the CoC was at treatment for all time periods. During the Unrestricted DAAs period, recent (past year) homelessness (vs never, aOR:0.66, 95 %CI:0.45-0.97), duration of injecting (≤3 years vs >3 years; aOR:0.26, 95 %CI:0.12-0.60), never (vs current, aOR:0.31, 95 %CI:0.13-0.75) or previously being prescribed OAT (vs current, aOR:0.67, 95 %CI:0.47-0.95), and never using a NSP (vs past year, aOR:0.27, 95 %CI:0.08-0.89) were negatively associated with lifetime HCV treatment. The proportion of PWID reporting recent HCV testing was higher during Unrestricted DAAs (56 %) compared to Pre-DAAs (48 %; aOR:1.28, 95 %CI:1.06-1.54). CONCLUSION: COC stages from seeing a specialist onwards improved after DAAs became widely available. Further improvements in HCV testing are needed to eliminate HCV in England.

Effect of Remote and Virtual Technology on Home Dialysis.

In the United States, regulatory changes dictate telehealth activities. Telehealth was available to patients on home dialysis as early as 2019, allowing patients to opt for telehealth with home as the originating site and without geographic restriction. In 2020, coronavirus disease 2019 was an unexpected accelerant for telehealth use in the United States. Within nephrology, remote patient monitoring has most often been applied to the care of patients on home dialysis modalities. The effect that remote and virtual technologies have on home dialysis patients, telehealth and health care disparities, and health care providers' workflow changes are discussed here. Moreover, the future use of remote and virtual technologies to include artificial intelligence and artificial neural network model to optimize and personalize treatments will be highlighted. Despite these advances in technology challenges continue to exist, leaving room for future innovation to improve patient health outcome and equity. Prospective studies are needed to further understand the effect of using virtual technologies and remote monitoring on home dialysis outcomes, cost, and patient engagement.

Exposure to polycyclic aromatic hydrocarbons, volatile organic compounds, and tobacco-specific nitrosamines and incidence of esophageal cancer.

BACKGROUND: Studying carcinogens in tobacco and nontobacco sources may be key to understanding the pathogenesis and geographic distribution of esophageal cancer. METHODS: The Golestan Cohort Study has been conducted since 2004 in a region with high rates of esophageal squamous cell carcinoma. For this nested study, the cases comprised of all incident cases by January 1, 2018; controls were matched to the case by age, sex, residence, time in cohort, and tobacco use. We measured urinary concentrations of 33 exposure biomarkers of nicotine, polycyclic aromatic hydrocarbons, volatile organic compounds, and tobacco-specific nitrosamines. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for associations between the 90th vs the 10th percentiles of the biomarker concentrations and incident esophageal squamous cell carcinoma. RESULTS: Among individuals who did not currently use tobacco (148 cases and 163 controls), 2 acrolein metabolites, 2 acrylonitrile metabolites, 1 propylene oxide metabolite, and one 1,3-butadiene metabolite were significantly associated with incident esophageal squamous cell carcinoma (adjusted odds ratios between 1.8 and 4.3). Among tobacco users (57 cases and 63 controls), metabolites of 2 other volatile organic compounds (styrene and xylene) were associated with esophageal squamous cell carcinoma (OR = 6.2 and 9.0, respectively). In tobacco users, 2 tobacco-specific nitrosamines (NNN and N'-Nitrosoanatabine) were also associated with esophageal squamous cell carcinoma. Suggestive associations were seen with some polycyclic aromatic hydrocarbons (especially 2-hydroxynaphthalene) in nonusers of tobacco products and other tobacco-specific nitrosamines in tobacco users. CONCLUSION: These novel associations based on individual-level data and samples collected many years before cancer diagnosis, from a population without occupational exposure, have important public health implications.

Esophagectomy Enhanced Recovery After Surgery Initiative Results in Improved Outcomes.

BACKGROUND: Esophagectomy for esophageal cancer is a procedure with high morbidity and mortality. This study developed a Multidisciplinary Esophagectomy Enhanced Recovery Initiative (MERIT) pathway and analyzed implementation outcomes in a single institution. METHODS: The MERIT pathway was developed as a practice optimization and quality improvement initiative. Patients were studied from November 1, 2021 to June 20, 2022 and were compared with historical control subjects. The Wilcoxon rank sum test and the Fisher exact test were used for statistical analysis. RESULTS: The study compared 238 historical patients (January 17, 2017 to December 30, 2020) with 58 consecutive MERIT patients. There were no significant differences between patient characteristics in the 2 groups. In the MERIT group, 49 (85%) of the patients were male, and their mean age was 65 years (range, 59-71 years). Most cases were performed for esophageal cancer after neoadjuvant therapy. Length of stay improved by 27% from 11 to 8 days (P = .27). There was a 12% (P = .05) atrial arrhythmia rate reduction, as well as a 9% (P = .01) decrease in postoperative ileus. Overall complications were reduced from 54% to 35% (-19%; P = .01). CONCLUSIONS: This study successfully developed and implemented an enhanced recovery after surgery pathway for esophagectomy. In the first year, study investigators were able to reduce overall complications, specifically atrial arrhythmias, and postoperative ileus.