The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study.

Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression. Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL. We aim to recruit 150 participants with diagnosed CADASIL, family history of CADASIL or suspected CADASIL symptoms, and 150 cognitively normal NOTCH3 negative individuals as controls. Participants will complete: 1) online questionnaires on medical and family history, mental health, and wellbeing; 2) neuropsychological evaluation; 3) neurological examination and brain MRI; 4) ocular examination and 5) blood sample donation. Participants will have annual follow-up for 4 years to assess their progression and will be asked to invite a study partner to corroborate their self-reported cognitive and functional abilities.Primary outcomes include cognitive function and neuroimaging abnormalities. Secondary outcomes include investigation of genetics and blood and ocular biomarkers. Data from the cohort will contribute to an international consortium, and cohort participants will be invited to access future treatment/health intervention trials. Discussion: AusCADASIL will be the first study of an Australian cohort of individuals with CADASIL. The study will identify common pathogenic variants in this cohort, and characterise the pattern of clinical presentation and longitudinal progression, including imaging features, blood and ocular biomarkers and cognitive profile.

Re-repair for mitral insufficiency.

BACKGROUND: Mitral valve repair provides superior outcomes to replacement for primary MR. Whether this is true following previous repair is unknown. We present the results of a strategy of re-repair for failed mitral valve repair. We examine patients who were brought to the operating room for an intended mitral valve re-repair. METHODS: We reviewed the last one decade of our institutional mitral valve databases at The University of Pennsylvania and Plano Heart Hospital and identified patients undergoing repeat mitral valve repair, in whom the index operation was mitral valve repair. We analyzed their operative details, clinical and echocardiographic outcomes. RESULTS: Between 2008 and 2021, 71 patients (aged 61.5 ±10.7 years, 20% female) underwent mitral valve reoperation at an mean of 6.24 ±7.62 years following index mitral repair. 20% of patients presented with NYHA class III/IV symptoms. At index operation, 34 (47.9%) had repair through a right mini-thoracotomy. 15 patients (21.1%) required the reoperation within one year. There were 0 early and 8 late deaths. One patient who underwent mitral replacement instead of repair, required reoperation for paravalvular leak during the follow-up period. Three patients required mitral valve replacement at an average of 2.28 ±2.03 years following initial mitral valve re-repair. CONCLUSIONS: Mitral re-repair can be performed with acceptable results at a valve reference center. Durability and functional advantages of this approach remain to be proven.

Microbial diversity, genomics, and phage-host interactions of cyanobacterial harmful algal blooms.

The occurrence of cyanobacterial harmful algal blooms (cyanoHABs) is related to their physical and chemical environment. However, less is known about their associated microbial interactions and processes. In this study, cyanoHABs were analyzed as a microbial ecosystem, using 1 year of 16S rRNA sequencing and 70 metagenomes collected during the bloom season from Lake Okeechobee (Florida, USA). Biogeographical patterns observed in microbial community composition and function reflected ecological zones distinct in their physical and chemical parameters that resulted in bloom "hotspots" near major lake inflows. Changes in relative abundances of taxa within multiple phyla followed increasing bloom severity. Functional pathways that correlated with increasing bloom severity encoded organic nitrogen and phosphorus utilization, storage of nutrients, exchange of genetic material, phage defense, and protection against oxidative stress, suggesting that microbial interactions may promote cyanoHAB resilience. Cyanobacterial communities were highly diverse, with picocyanobacteria ubiquitous and oftentimes most abundant, especially in the absence of blooms. The identification of novel bloom-forming cyanobacteria and genomic comparisons indicated a functionally diverse cyanobacterial community with differences in its capability to store nitrogen using cyanophycin and to defend against phage using CRISPR and restriction-modification systems. Considering blooms in the context of a microbial ecosystem and their interactions in nature, physiologies and interactions supporting the proliferation and stability of cyanoHABs are proposed, including a role for phage infection of picocyanobacteria. This study displayed the power of "-omics" to reveal important biological processes that could support the effective management and prediction of cyanoHABs. IMPORTANCE: Cyanobacterial harmful algal blooms pose a significant threat to aquatic ecosystems and human health. Although physical and chemical conditions in aquatic systems that facilitate bloom development are well studied, there are fundamental gaps in the biological understanding of the microbial ecosystem that makes a cyanobacterial bloom. High-throughput sequencing was used to determine the drivers of cyanobacteria blooms in nature. Multiple functions and interactions important to consider in cyanobacterial bloom ecology were identified. The microbial biodiversity of blooms revealed microbial functions, genomic characteristics, and interactions between cyanobacterial populations that could be involved in bloom stability and more coherently define cyanobacteria blooms. Our results highlight the importance of considering cyanobacterial blooms as a microbial ecosystem to predict, prevent, and mitigate them.

Skeletal muscle desmin alterations following revascularization in peripheral artery disease claudicants.

Peripheral artery disease (PAD) is characterized by varying severity of arterial stenosis, exercise induced claudication, malperfused tissue precluding normal healing and skeletal muscle dysfunction. Revascularization interventions improve circulation, but post-reperfusion changes within the skeletal muscle are not well characterized. This study investigates if revascularization enhanced hemodynamics increases walking performance with concurrent improvement of mitochondrial function and reverses abnormal skeletal muscle morphological features that develop with PAD. Fifty-eight patients completed walking performance testing and muscle biopsy before and 6 months after revascularization procedures. Muscle fiber morphology, desmin structure, and mitochondria respiration assessments before and after the revascularization were evaluated. Revascularization improved limb hemodynamics, walking function, and muscle morphology. Qualitatively not all participants recovered normal structural architecture of desmin in the myopathic myofibers after revascularization. Heterogenous responses in the recovery of desmin structure following revascularization may be caused by other underlying factors not reversed with hemodynamic improvements. Revascularization interventions clinically improve patient walking ability and can reverse the multiple subcellular functional and structural abnormalities in muscle cells. Further study is needed to characterize desmin structural remodeling with improvements in skeletal muscle morphology and function.

Lung Cancer Screening in the US, 2022.

Importance: The US Preventive Services Task Force (USPSTF) recommends annual lung cancer screening (LCS) with low-dose computed tomography in high-risk individuals (age 50-80 years, ≥20 pack-years currently smoking or formerly smoked, and quit <15 years ago) for early detection of LC. However, representative state-level LCS data are unavailable nationwide. Objective: To estimate the contemporary prevalence of up-to-date (UTD) LCS in the US nationwide and across the 50 states and the District of Columbia. Design, Setting, and Participants: This cross-sectional study used data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS) population-based, nationwide, state-representative survey for respondents aged 50 to 79 years who were eligible for LCS according to the 2021 USPSTF eligibility criteria. Data analysis was performed from October 1, 2023, to March 20, 2024. Main Outcomes and Measures: The main outcome was self-reported UTD-LCS (defined as past-year) prevalence according to the 2021 USPSTF eligibility criteria in respondents aged 50 to 79 years. Adjusted prevalence ratios (APRs) and 95% CIs compared differences. Results: Among 25 958 sample respondents eligible for LCS (median [IQR] age, 62 [11] years), 61.5% reported currently smoking, 54.4% were male, 64.4% were aged 60 years or older, and 53.0% had a high school education or less. The UTD-LCS prevalence was 18.1% overall, but varied across states (range, 9.7%-31.0%), with relatively lower levels in southern states characterized by high LC mortality burden. The UTD-LCS prevalence increased with age (50-54 years: 6.7%; 70-79 years: 27.1%) and number of comorbidities (≥3: 24.6%; none: 8.7%). A total of 3.7% of those without insurance and 5.1% of those without a usual source of care were UTD with LCS, but state-level Medicaid expansions (APR, 2.68; 95% CI, 1.30-5.53) and higher screening capacity levels (high vs low: APR, 1.93; 95% CI, 1.36-2.75) were associated with higher UTD-LCS prevalence. Conclusions and Relevance: This study of data from the 2022 BRFSS found that the overall prevalence of UTD-LCS was low. Disparities were largest according to health care access and geographically across US states, with low prevalence in southern states with high LC burden. The findings suggest that state-based initiatives to expand access to health care and screening facilities may be associated with improved LCS rates and reduced disparities.

Factors associated with medical consumable availability in level 1 facilities in Malawi: a secondary analysis of a facility census.

BACKGROUND: Medical consumable stock-outs negatively affect health outcomes not only by impeding or delaying the effective delivery of services but also by discouraging patients from seeking care. Consequently, supply chain strengthening is being adopted as a key component of national health strategies. However, evidence on the factors associated with increased consumable availability is limited. METHODS: In this study, we used the 2018-19 Harmonised Health Facility Assessment data from Malawi to identify the factors associated with the availability of consumables in level 1 facilities, ie, rural hospitals or health centres with a small number of beds and a sparsely equipped operating room for minor procedures. We estimate a multilevel logistic regression model with a binary outcome variable representing consumable availability (of 130 consumables across 940 facilities) and explanatory variables chosen based on current evidence. Further subgroup analyses are carried out to assess the presence of effect modification by level of care, facility ownership, and a categorisation of consumables by public health or disease programme, Malawi's Essential Medicine List classification, whether the consumable is a drug or not, and level of average national availability. FINDINGS: Our results suggest that the following characteristics had a positive association with consumable availability-level 1b facilities or community hospitals had 64% (odds ratio [OR] 1·64, 95% CI 1·37-1·97) higher odds of consumable availability than level 1a facilities or health centres, Christian Health Association of Malawi and private-for-profit ownership had 63% (1·63, 1·40-1·89) and 49% (1·49, 1·24-1·80) higher odds respectively than government-owned facilities, the availability of a computer had 46% (1·46, 1·32-1·62) higher odds than in its absence, pharmacists managing drug orders had 85% (1·85, 1·40-2·44) higher odds than a drug store clerk, proximity to the corresponding regional administrative office (facilities greater than 75 km away had 21% lower odds [0·79, 0·63-0·98] than facilities within 10 km of the district health office), and having three drug order fulfilments in the 3 months before the survey had 14% (1·14, 1·02-1·27) higher odds than one fulfilment in 3 months. Further, consumables categorised as vital in Malawi's Essential Medicine List performed considerably better with 235% (OR 3·35, 95% CI 1·60-7·05) higher odds than other essential or non-essential consumables and drugs performed worse with 79% (0·21, 0·08-0·51) lower odds than other medical consumables in terms of availability across facilities. INTERPRETATION: Our results provide evidence on the areas of intervention with potential to improve consumable availability. Further exploration of the health and resource consequences of the strategies discussed will be useful in guiding investments into supply chain strengthening. FUNDING: UK Research and Innovation as part of the Global Challenges Research Fund (Thanzi La Onse; reference MR/P028004/1), the Wellcome Trust (Thanzi La Mawa; reference 223120/Z/21/Z), the UK Medical Research Council, the UK Department for International Development, and the EU (reference MR/R015600/1).

The network structures of mental and behavioral problems among children and adolescents in China using propensity score matching: A comparison between one-child and multi-child families based on a nationwide survey.

BACKGROUND: Exploring networks of mental and behavioral problems in children and adolescents may identify differences between one-child and multi-child families. This study compared the network structures of mental and behavioral problems in children and adolescents in one-child families versus multi-child families based on a nationwide survey. METHODS: Propensity score matching (PSM) was used to match children and adolescents from one-child families with those from multi-child families. Mental and behavioral problems were assessed using the Achenbach's Child Behavior Checklist (CBCL) with eight syndromal subscales. In the network analysis, strength centrality index was used to estimate central symptoms, and case-dropping bootstrap method was used to assess network stability. RESULTS: The study included 39,648 children and adolescents (19,824 from one-child families and 19,824 from multi-child families). Children and adolescents from multi-child families exhibited different network structure and higher global strength compared to those from one-child families. In one-child families, the most central symptoms were "Social problems", "Anxious/depressed" and "Withdrawn/depressed", while in multi-child families, the most central symptoms were "Social problems", "Rule-breaking behavior" and "Anxious/depressed". CONCLUSION: Differences in mental and behavioral problems among children and adolescents between one-child and multi-child families were found. To address these problems, interventions targeting "Social problems" and "Anxious/depressed" symptoms should be developed for children and adolescents in both one-child and multi-child families, while other interventions targeting "Withdrawn/depressed" and "Rule-breaking behavior" symptoms could be useful for those in one-child and multi-child families, respectively.

Purine and pyrimidine synthesis differently affect the strength of the inoculum effect for aminoglycoside and ß-lactam antibiotics.

The inoculum effect has been observed for nearly all antibiotics and bacterial species. However, explanations accounting for its occurrence and strength are lacking. We previously found that growth productivity, which captures the relationship between [ATP] and growth, can account for the strength of the inoculum effect for bactericidal antibiotics. However, the molecular pathway(s) underlying this relationship, and therefore determining the inoculum effect, remain undiscovered. We show that nucleotide synthesis can determine the relationship between [ATP] and growth, and thus the strength of inoculum effect in an antibiotic class-dependent manner. Specifically, and separate from activity through the tricarboxylic acid cycle, we find that transcriptional activity of genes involved in purine and pyrimidine synthesis can predict the strength of the inoculum effect for ß-lactam and aminoglycosides antibiotics, respectively. Our work highlights the antibiotic class-specific effect of purine and pyrimidine synthesis on the severity of the inoculum effect and paves the way for intervention strategies to reduce the inoculum effect in the clinic.

The Effects of Anchoring a Fatiguing Forearm Flexion Task to a High vs. Low Rating of Perceived Exertion on Torque and Neuromuscular Responses.

ABSTRACT: Ortega, DG, Housh, TJ, Smith, RW, Arnett, JE, Neltner, TJ, Schmidt, RJ, and Johnson, GO. The effects of anchoring a fatiguing forearm flexion task to a high versus low rating of perceived exertion on torque and neuromuscular responses. J Strength Cond Res 38(5): e219-e225, 2024-This study examined the torque and neuromuscular responses following sustained, isometric, forearm flexion tasks anchored to 2 ratings of perceived exertion (RPE). Nine men (mean ± SD: age = 21.0 ± 2.4 years; height = 179.5 ± 5.1 cm; body mass = 79.6 ± 11.4 kg) completed maximal voluntary isometric contractions (MVIC) before and after sustained, isometric, forearm flexion tasks to failure anchored to RPE = 2 and RPE = 8. The amplitude (AMP) and mean power frequency (MPF) of the electromyographic (EMG) signal were recorded from the biceps brachii. Normalized torque was divided by normalized EMG AMP to calculate neuromuscular efficiency (NME). A dependent t-test was used to assess the mean difference for time to task failure (TTF). Repeated-measures analysis of variances was used to compare mean differences for MVIC and normalized neuromuscular parameters. There was no significant difference in TTF between RPE = 2 and RPE = 8 (p = 0.713). The MVIC decreased from pretest to posttest at RPE = 2 (p = 0.009) and RPE = 8 (p = 0.003), and posttest MVIC at RPE = 8 was less than that at RPE = 2 (p < 0.001). In addition, NME decreased from pretest to posttest (p = 0.008). There was no change in normalized EMG AMP or EMG MPF (p > 0.05). The current findings indicated that torque responses were intensity specific, but TTF and neuromuscular responses were not. Furthermore, normalized EMG AMP and EMG MPF remained unchanged but NME decreased, likely due to peripheral fatigue and excitation-contraction coupling failure. Thus, this study provides information regarding the neuromuscular responses and mechanisms of fatigue associated with tasks anchored to RPE, which adds to the foundational understanding of the relationship between resistance exercise and the perception of fatigue.

Rapid Metabolism Underlying Subtherapeutic Serum Levels of Atypical Antipsychotics Preceding Clozapine Treatment: A Retrospective Analysis of Real-World Data.

INTRODUCTION: Adequate antipsychotic treatment intensity is required before diagnosing resistant schizophrenia and initiating clozapine treatment. We aimed to investigate potential rapid drug metabolism underlying low dose-adjusted serum concentration (CD) of non-clozapine atypical antipsychotics preceding clozapine treatment. METHODS: Patients using non-clozapine, atypical antipsychotics (aripiprazole, risperidone, olanzapine, or quetiapine) within 1 year before starting clozapine were included in this study from a therapeutic drug monitoring service in Oslo, Norway, between 2005 and 2023. Patients were assigned into low CD (LCD) and normal CD (NCD) subgroups. Using a reference sample with 147,964 antipsychotic measurements, LCD was defined as CDs below the 25th percentile, while patients with NCD exhibited CDs between the 25th and 75th percentile of the respective reference measurements. Metabolic ratios, doses, and frequency of subtherapeutic levels of non-clozapine antipsychotics were compared between LCD and NCD groups. RESULTS: Preceding clozapine treatment, 110 out of 272 included patients (40.4%) were identified with LCD. Compared with the NCD group, LCD patients exhibited higher metabolic ratios of olanzapine (1.5-fold; p < 0.001), quetiapine (3.0-fold; p < 0.001), and risperidone (6.0-fold; p < 0.001). Metabolic ratio differences were independent of smoking and CYP2D6 genotype for olanzapine (p = 0.008) and risperidone (p = 0.016), respectively. Despite higher doses of olanzapine (1.25-fold; p = 0.054) and quetiapine (1.6-fold; p = 0.001) in LCD versus NCD patients, faster metabolism among the former was accompanied by higher frequencies of subtherapeutic levels of olanzapine (3.3-fold; p = 0.044) and quetiapine (1.8-fold; p = 0.005). CONCLUSION: LCD and associated rapid metabolism of non-clozapine antipsychotics is frequent before starting clozapine treatment. For olanzapine and quetiapine, this is associated with significantly increased risk of having subtherapeutic concentrations.

Protocol for nanoscale thermal mapping of electronic devices using atomic force microscopy with phase change material.

In this protocol, we present a facile nanoscale thermal mapping technique for electronic devices by use of atomic force microscopy and a phase change material Ge2Sb2Te5. We describe steps for Ge2Sb2Te5 thin film coating, Ge2Sb2Te5 temperature calibration, thermal mapping by varying heater power, and thermal mapping by varying heating time. The protocol can be applied for resolving surface temperatures of various operational microelectronic devices with a nanoscale precision. For complete details on the use and execution of this protocol, please refer to Cheng et al.1.

Porcine-derived collagen peptides promote re-epithelialisation through activation of integrin signalling.

Chronic non-healing cutaneous wounds represent a major burden to patients and healthcare providers worldwide, emphasising the continued unmet need for credible and efficacious therapeutic approaches for wound healing. We have recently shown the potential for collagen peptides to promote proliferation and migration during cutaneous wound healing. In the present study, we demonstrate that the application of porcine-derived collagen peptides significantly increases keratinocyte and dermal fibroblast expression of integrin α2ß1 and activation of an extracellular signal-related kinase (ERK)-focal adhesion kinase (FAK) signalling cascade during wound closure in vitro. SiRNA-mediated knockdown of integrin ß1 impaired porcine-derived collagen peptide-induced wound closure and activation of ERK-FAK signalling in keratinocytes but did not impair ERK or FAK signalling in dermal fibroblasts, implying the activation of differing downstream signalling pathways. Studies in ex vivo human 3D skin equivalents subjected to punch biopsy-induced wounding confirmed the ability of porcine-derived collagen peptides to promote wound closure by enhancing re-epithelialisation. Collectively, these data highlight the translational and clinical potential for porcine-derived collagen peptides as a viable therapeutic approach to promote re-epithelialisation of superficial cutaneous wounds.

Comparison of Transcatheter Edge-to-Edge Mitral Valve Repair for Primary Mitral Regurgitation Outcomes to Hospital Volumes of Surgical Mitral Valve Repair.

BACKGROUND: Transcatheter edge-to-edge mitral valve (MV) repair (TEER) is an effective treatment for patients with primary mitral regurgitation at prohibitive risk for surgical MV repair (MVr). High-volume MVr centers and high-volume TEER centers have better outcomes than low-volume centers, respectively. However, whether MVr volume predicts TEER outcomes remains unknown. We hypothesized that high-volume MV surgical centers would have superior risk-adjusted outcomes for TEER than low-volume centers. METHODS: We combined data from the American College of Cardiology/Society of Thoracic Surgeons Transcatheter Valve Therapy registry and the Society of Thoracic Surgeons adult cardiac surgery database. MVr was defined as leaflet resection or artificial chords with or without annuloplasty and was evaluated as a continuous variable and as predefined categories (<25, 25-49, and ≥50 MV repairs/year). A generalized linear mixed model was used to evaluate risk-adjusted in-hospital/30-day mortality, 30-day heart failure readmission, and TEER success (mitral regurgitation ≤2+ and gradient <5 mm Hg). RESULTS: The study comprised 41 834 patients from 500 sites of which 332 (66.4%) were low, 102 (20.4%) intermediate, and 66 (13.2%) high-volume surgical centers (P<0.001). TEER success was 54.6% and was not statistically significantly different across MV surgical site volumes (P=0.4271). TEER mortality at 30 days was 3.5% with no significant difference across MVr volume on unadjusted (P=0.141) or adjusted (P=0.071) analysis of volume as a continuous variable. One-year mortality was 15.0% and was lower for higher MVr volume centers when adjusted for clinical and demographic variables (P=0.027). Heart failure readmission at 1 year was 9.4% and was statistically significantly lower in high-volume centers on both unadjusted (P=0.017) or adjusted (P=0.015) analysis. CONCLUSIONS: TEER can be safely performed in centers with low volumes of MV repair. However, 1-year mortality and heart failure readmission are superior at centers with higher MVr volume.

Automated dairy cattle lameness detection utilizing the power of artificial intelligence; current status quo and future research opportunities.

Lameness represents a major welfare and health problem for the dairy industry across all farming systems. Visual mobility scoring, although very useful, is labour-intensive and physically demanding, especially in large dairies, often leading to inconsistencies and inadequate uptake of the practice. Technological and computational advancements of artificial intelligence (AI) have led to the development of numerous automated solutions for livestock monitoring. The objective of this study was to review the automated systems using AI algorithms for lameness detection developed to-date. These systems rely on gait analysis using accelerometers, weighing platforms, acoustic analysis, radar sensors and computer vision technology. The lameness features of interest, the AI techniques used to process the data as well as the ground truth of lameness selected in each case are described. Measures of accuracy regarding correct classification of cows as lame or non-lame varied with most systems being able to classify cows with adequate reliability. Most studies used visual mobility scoring as the ground truth for comparison with only a few studies using the presence of specific foot pathologies. Given the capabilities of AI, and the benefits of early treatment of lameness, longitudinal studies to identify gait abnormalities using automated scores related to the early developmental stages of different foot pathologies are required. Farm-specific optimal thresholds for early intervention should then be identified to ameliorate cow health and welfare but also minimise unnecessary inspections.

Industry Perceptions and Experiences with the Access Consortium New Active Substance Work-Sharing Initiative (NASWSI): Survey Results and Recommendations.

The Access Consortium New Active Substance Work-Sharing Initiative, or "Access" for simplicity, allows regulatory authorities (RAs) of the Access Consortium countries to jointly review applications for the registration of new active substances or for new indications. Using a survey developed by the pharmaceutical industry trade associations of the five Access Consortium countries-Australia, Canada, Singapore, Switzerland, and the United Kingdom (UK)-this study gathered insights into the perceptions and experiences of the Access pathway held by affiliates of pharmaceutical companies. Understanding industry perceptions of Access is important for the success of the initiative, as participation is voluntary. Findings indicate that affiliates who participated in Access had mostly positive experiences with this pathway; most affiliates were satisfied with their interactions with the Access RAs and appeared willing to continue to participate in the initiative. Affiliates' reasons for not having yet participated in Access included a lack of opportunity to do so and perceived barriers, such as the Access pathway being too complicated to manage. Recommendations to improve Access cover six key areas: ensure predictability, increase guidance and transparency, streamline processes, maintain flexibility, increase harmonization, and advance RA-industry cooperation. This study should facilitate informed discussions among relevant stakeholders on how to improve Access to maximize efficiencies, accelerate approvals, and improve patient access to innovative medicines.

A comparison of radiographically determined periapical healing and tooth survival outcomes of root canal (re)treatment performed in two care pathways within the United Kingdom Armed Forces.

AIMS: To compare radiographic periapical healing and tooth survival outcomes of root canal (re)treatment performed within two care pathways (Routine Dental Care and Referred Treatment Pathway), in the United Kingdom Armed Forces (UKAF), and determine the effects of endodontic complexity on outcomes. METHODOLOGY: This retrospective cohort study included 1466 teeth in 1252 personnel who received root canal (re)treatment between 2015 and 2020. General Dental Practitioners treated 661 teeth (573 patients) (Routine cohort), whilst Dentists with a Special Interest treated 805 teeth (678 patients) (Referred cohort). The latter group were graduates of an MSc programme in Endodontics with 4-8 years of postgraduation experience. Case complexity was retrospectively determined for each tooth using the endodontic component of Restorative Index of Treatment Need (RIOTN) guidelines. Periapical healing was determined using loose radiographic criteria. The data were analysed using chi-square tests, univariate logistic regression and Cox proportional hazards models. RESULTS: A significantly (p < 0.0001) larger proportion of cases of low complexity had undergone root canal treatment within the Routine versus Referred cohort. The odds of periapical healing was significantly higher within the Referred versus Routine cohort, regardless of analyses using pooled (OR = 1.17; 95% CI: 1.11, 1.22) or moderate complexity (OR = 4.71; 95% CI: 2.73, 8.11) data. Within the Routine cohort, anterior teeth had higher odds of periapical healing than posterior teeth (OR = 1.13; 95% CI: 1.04, 1.22). The 60-month cumulative tooth survival was lower (p = 0.03) in the Routine (90.5%) than the Referred (96.0%) cohort. Within the Routine cohort, the hazard of tooth loss was higher amongst posterior teeth (HR = 4.03; 95% CI: 1.92, 8.45) but lower if posterior teeth had cast restorations (HR = 0.36; 95% CI: 0.19, 0.70). For the Referred cohort, posterior teeth restored with cast restoration (vs not) had significantly lower risk of tooth loss (HR = 0.21; 95% CI: 0.08, 0.55). CONCLUSIONS: For UKAF patients, root canal (re)treatment provided within the Referred pathway was significantly more likely to achieve periapical healing and better tooth survival than those provided within the Routine pathway. Posterior teeth restored with an indirect restoration had a higher proportion of tooth survival. This study supported the utility of the endodontic component of RIOTN for assessing case complexity.

Implementation and Validation of an Automated, Longitudinal Robotic Surgical Evaluation and Feedback Program at a High-volume Center and Impact on Training.

Background: Surgical education lacks a standardized, proficiency-based approach to evaluation and feedback. Objective: To assess the implementation and reception (ie, feasibility) of an automated, standardized, longitudinal surgical skill assessment and feedback system, and identify baseline trainee (resident and fellow) characteristics associated with achieving proficiency in robotic surgery while learning robotic-assisted laparoscopic prostatectomy. Design setting and participants: A quality improvement study assessing a pilot of a surgical experience tracking program was conducted over 1 yr. Participants were six fellows, eight residents, and nine attending surgeons at a tertiary cancer center. Intervention: Trainees underwent baseline self-assessment. After each surgery, an evaluation was completed independently by the trainee and attending surgeons. Performance was rated on a five-point anchored Likert scale (trainees were considered "proficient" when attending surgeons' rating was ≥4). Technical skills were assessed using the Global Evaluative Assessment of Robotic Skills (GEARS) and Prostatectomy Assessment and Competency Evaluation (PACE). Outcome measurements and statistical analysis: Program success and utility were assessed by evaluating completion rates, evaluation completion times, and concordance rates between attending and trainee surgeons, and exit surveys. Baseline characteristics were assessed to determine associations with achieving proficiency. Results and limitations: Completion rates for trainees and attending surgeons were 72% and 77%, respectively. Fellows performed more steps/cases than residents (median [interquartile range]: 5 [3-7] and 3 [2-4], respectively; p < 0.01). Prior completion of robotics or laparoscopic skill courses and surgical experience measures were associated with achieving proficiency in multiple surgical steps and GEARS domains. Interclass correlation coefficients on individual components were 0.27-0.47 on GEARS domains. Conclusions: An automated surgical experience tracker with structured, longitudinal evaluation and feedback can be implemented with good participation and minimal participant time commitment, and can guide curricular development in a proficiency-based education program by identifying modifiable factors associated with proficiency, individualizing education, and identifying improvement areas within the education program. Patient summary: An automated, standardized, longitudinal surgical skill assessment and feedback system can be implemented successfully in surgical education settings and used to inform education plans and predict trainee proficiency.