Assessing Circulating Tumour DNA (ctDNA) as a Biomarker for Anal Cancer Management: A Systematic Review.

This systematic review investigates the potential of circulating tumour DNA (ctDNA) as a predictive biomarker in the management and prognosis of squamous cell carcinoma of the anal canal (SCCA). PubMed, EMBASE, and Cochrane Central Registry of Controlled Trials were searched until 7 January 2024. Selection criteria included research articles exploring ctDNA in the context of anal cancer treatment response, recurrence risk assessment, and consideration of salvage surgery. A total of eight studies were therefore included in the final review, examining a total of 628 patients. These studies focused on three main themes: SCCA diagnosis and staging, treatment response, and patient outcomes. Significant heterogeneity was observed in terms of patient cohort, study methodology, and ctDNA biomarkers. Four studies provided information on the sensitivity of ctDNA biomarkers in SCCA, with a range of 82-100%. Seven studies noted a correlation between pre-treatment ctDNA levels and SCCA disease burden, suggesting that ctDNA could play a role as a biomarker for the staging of SCCA. Across all seven studies with paired pre- and post-treatment ctDNA samples, a trend was seen towards decreasing ctDNA levels post-treatment, with specific identification of a 'fast elimination' group who achieve undetectable ctDNA levels prior to the end of treatment and may be less likely to experience treatment failure. Residual ctDNA detection post-treatment was associated with poorer patient prognosis. This systematic review identifies the broad potential of ctDNA as a useful and decisive tool in the management of SCCA. Further analysis of ctDNA biomarkers that include larger patient cohorts is required in order to clearly evaluate their potential role in clinical decision-making processes.

Elevating understanding: Linking high-altitude hypoxia to brain aging through EEG functional connectivity and spectral analyses.

High-altitude hypoxia triggers brain function changes reminiscent of those in healthy aging and Alzheimer's disease, compromising cognition and executive functions. Our study sought to validate high-altitude hypoxia as a model for assessing brain activity disruptions akin to aging. We collected EEG data from 16 healthy volunteers during acute high-altitude hypoxia (at 4,000 masl) and at sea level, focusing on relative changes in power and aperiodic slope of the EEG spectrum due to hypoxia. Additionally, we examined functional connectivity using wPLI, and functional segregation and integration using graph theory tools. High altitude led to slower brain oscillations, that is, increased δ and reduced α power, and flattened the 1/f aperiodic slope, indicating higher electrophysiological noise, akin to healthy aging. Notably, functional integration strengthened in the θ band, exhibiting unique topographical patterns at the subnetwork level, including increased frontocentral and reduced occipitoparietal integration. Moreover, we discovered significant correlations between subjects' age, 1/f slope, θ band integration, and observed robust effects of hypoxia after adjusting for age. Our findings shed light on how reduced oxygen levels at high altitudes influence brain activity patterns resembling those in neurodegenerative disorders and aging, making high-altitude hypoxia a promising model for comprehending the brain in health and disease.

Exposure to high-altitude hypoxia, with reduced oxygen levels, can replicate brain function changes akin to aging and Alzheimer's disease. In our work, we propose high-altitude hypoxia as a possible reversible model of human brain aging. We gathered EEG data at high altitude and sea level, investigating the impact of hypoxia on brainwave patterns and connectivity. Our findings revealed that high-altitude exposure led to slower and noisier brain oscillations and produced altered brain connectivity, resembling some remarkable changes seen in the aging process. Intriguingly, these changes were linked to age, even when hypoxia's effects were considered. Our research unveils how high-altitude conditions emulate brain patterns associated with aging and neurodegenerative conditions, providing valuable insights into the understanding of both normal and impaired brain function.

Whole-Body MRI Screening for Carriers of Germline TP53 Mutations-A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review evaluated whole-body MRI (WB-MRI) as a cancer screening tool for individuals carrying germline TP53 mutations, a population known to be at a significantly elevated risk of malignancy. The primary objective is to assess the diagnostic performance of WB-MRI in detecting cancer in this cohort. METHODS: PubMed, MEDLINE, EMBASE and the Cochrane Central Registry of Controlled Trials were searched until 18 August 2023. Eligible studies were selected based on predefined inclusion criteria. The data extracted included information on study characteristics, patient demographics, and the WB-MRI diagnostic performance. RESULTS: This systematic review identified eight eligible studies, comprising 506 TP53 mutation carriers. The mean age was 34.6 ± 16.3 (range 1-74) years. In total, 321/506 (63.4%) of the patients were female and 185/506 (36.6%) were male. In addition, 267/506 (52.8%) had a previous oncological diagnosis. Thirty-six new cancers were diagnosed with WB-MRI (36/506 (7.1%)). The overall pooled proportion of cancer detected on MRI was 7% (95% confidence interval 5-10). In total, 44 new lesions were picked up, as multiple lesions were found in some patients. CONCLUSION: WB-MRI is an effective cancer screening tool for TP53 mutation carriers. While these findings suggest the potential for WB-MRI to contribute to early cancer detection in this high-risk population, further research and the standardisation of protocols internationally are warranted to optimise its clinical utility.

Central nervous system medication use around hospitalization.

BACKGROUND: Central nervous system (CNS) medication use is common among older adults, yet the impact of hospitalizations on use remains unclear. This study details CNS medication use, discontinuations, and user profiles during hospitalization periods. METHODS: Retrospective cohort study using electronic health records on patients ≥65 years, from three hospitals (2018-2020), and prescribed a CNS medication around hospitalization (90 days prior to 90 days after). Latent class transitions analysis (LCTA) examined profiles of CNS medication class users across four time points (90 days prior, admission, discharge, 90 days after hospitalization). RESULTS: Among 4666 patients (mean age 74.3 ± 9.3 years; 63% female; 70% White; mean length of stay 4.6 ± 5.6 days (median 3.0 [2.0, 6.0]), the most commonly prescribed CNS medications were antidepressants (56%) and opioids (49%). Overall, 74% (n = 3446) of patients were persistent users of a CNS medication across all four time points; 7% (n = 388) had discontinuations during hospitalization, but of these, 64% (216/388) had new starts or restarts within 90 days after hospitalization. LCTA identified three profile groups: (1) low CNS medication users, 54%-60% of patients; (2) mental health medication users, 30%-36%; and (3) acute/chronic pain medication users, 9%-10%. Probability of staying in same group across the four time points was high (0.88-1.00). Transitioning to the low CNS medication use group was highest from admission to discharge (probability of 9% for pain medication users, 5% for mental health medication users). Female gender increased (OR 2.4, 95% CI 1.3-4.3), while chronic kidney disease lowered (OR 0.5, 0.2-0.9) the odds of transitioning to the low CNS medication use profile between admission and discharge. CONCLUSIONS: CNS medication use stays consistent around hospitalization, with discontinuation more likely between admission and discharge, especially among pain medication users. Further research on patient outcomes is needed to understand the benefits and harms of hospital deprescribing, particularly for medications requiring gradual tapering.

Quality of vision and tear film osmolarity.

SIGNIFICANCE: We evaluate the relationship between tear film osmolarity measurements and quality of vision in patients presenting for routine eye clinic appointments. We found that the hyperosmolar group (>316 mOsm/L) had a worse quality-of-vision score than the normal osmolarity group, with glare being the most problematic symptom. PURPOSE: Quality of vision is a perception and measure of real-world vision, which is not measured routinely in a clinical setting. This study aimed to evaluate the relationship between tear film osmolarity measurements and quality of vision in patients presenting for routine eye clinic appointments. METHODS: This was an observational nonrandomized study. The participants were placed in groups based on tear film osmolarity (normal, ≤316 mOsm/L; hyperosmolar, >316 mOsm/L; or a difference of >8 mOsm/L between each eye). Thirty-three participants were enrolled in the study, of whom 22 were deemed to have a hyperosmolar tear film. A 30-item questionnaire including 10 symptoms rated on scales of frequency, severity, and bothersomeness was administered to participants in both groups. The quality-of-vision score ranged from 25 to 100 points, with lower scores indicating better quality of vision. RESULTS: The hyperosmolar group had a significantly worse quality-of-vision score than the normal osmolarity group across all three scales; mean differences for frequency, severity, and bothersomeness were 12.66 ± 9.75 (p=0.003), 9.44 ± 7.45 (p=0.003), and 11.90 ± 11.14 (p=0.008), respectively. Of the 10 symptoms that were included in the questionnaire, glare was the most problematic in the hyperosmolar group. CONCLUSIONS: In this study, we demonstrated a significant relationship between tear film hyperosmolarity and quality of vision, as patients with hyperosmolar tear films had worse quality of vision.

Modifiable Risk Factors and Risk of Colorectal and Endometrial Cancers in Lynch Syndrome: A Systematic Review and Meta-Analysis.

PURPOSE: Lynch syndrome is the most common hereditary cause of colorectal and endometrial cancers. Modifiable risk factors, including obesity, physical activity, alcohol intake, and smoking, are well-established in sporadic cancers but are less studied in Lynch syndrome. METHODS: Searches were conducted on MEDLINE, Embase, and Web of Science for cohort studies that investigated the association between modifiable risk factors and the risk of colorectal or endometrial cancer in people with Lynch syndrome. Adjusted hazard ratios (HRs) and 95% CIs for colorectal and endometrial cancers were pooled using a random effects model. The protocol was prospectively registered on PROSPERO (CRD 42022378462), and the meta-analysis was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology reporting guidelines. RESULTS: A total of 770 citations were reviewed. Eighteen studies were identified for qualitative synthesis, with seven colorectal cancer (CRC) studies eligible for meta-analysis. Obesity (HR, 2.38 [95% CI, 1.52 to 3.73]) was associated with increased CRC risk. There was no increased CRC risk associated with smoking (HR, 1.04 [95% CI, 0.82 to 1.32]) or alcohol intake (HR, 1.32 [95% CI, 0.97 to 1.81]). Type 2 diabetes mellitus (T2DM) and some dietary factors might increase risk of CRC although more studies are needed. In a qualitative synthesis of three endometrial cancer cohort studies, female hormonal risk factors and T2DM may affect the risk of endometrial cancer, but obesity was not associated with an increased risk. CONCLUSION: Lifestyle recommendations related to weight and physical activity may also be relevant to cancer prevention for individuals with Lynch syndrome. Further high-quality prospective cohort studies, in particular, including endometrial cancer as an end point, are needed to inform evidence-based cancer prevention strategies in this high-risk population.

Translating ethical and quality principles for the effective, safe and fair development, deployment and use of artificial intelligence technologies in healthcare.

OBJECTIVE: The complexity and rapid pace of development of algorithmic technologies pose challenges for their regulation and oversight in healthcare settings. We sought to improve our institution's approach to evaluation and governance of algorithmic technologies used in clinical care and operations by creating an Implementation Guide that standardizes evaluation criteria so that local oversight is performed in an objective fashion. MATERIALS AND METHODS: Building on a framework that applies key ethical and quality principles (clinical value and safety, fairness and equity, usability and adoption, transparency and accountability, and regulatory compliance), we created concrete guidelines for evaluating algorithmic technologies at our institution. RESULTS: An Implementation Guide articulates evaluation criteria used during review of algorithmic technologies and details what evidence supports the implementation of ethical and quality principles for trustworthy health AI. Application of the processes described in the Implementation Guide can lead to algorithms that are safer as well as more effective, fair, and equitable upon implementation, as illustrated through 4 examples of technologies at different phases of the algorithmic lifecycle that underwent evaluation at our academic medical center. DISCUSSION: By providing clear descriptions/definitions of evaluation criteria and embedding them within standardized processes, we streamlined oversight processes and educated communities using and developing algorithmic technologies within our institution. CONCLUSIONS: We developed a scalable, adaptable framework for translating principles into evaluation criteria and specific requirements that support trustworthy implementation of algorithmic technologies in patient care and healthcare operations.

Development of an Emergency Department Case Management Case-Finding Tool.

PURPOSE OF STUDY: Identifying emergency department (ED) patients who are at high risk for return visits is an important goal for case management to improve patient care. This quality improvement study describes the development and evaluation of the Emergency Department Case Management Priority Score (EDCMPS), an electronic medical record (EMR)-based "case-finding" system, and its ability to identify these high-risk patients. In addition, the authors present data about its acceptability among emergency department case managers (ED CMs). PRIMARY PRACTICE SETTINGS: Emergency departments with case management availability and staffing. METHODOLOGY AND SAMPLE: A retrospective analysis at Duke University Hospital ED compared patient data pre- and postimplementation of the EDCMPS. The tool was developed using the LEAN and Plan-Do-Study-Act (PDSA) quality improvement methodologies, with ED CM participation. ED return and hospitalization rates within 7 and 30 days between both methods were compared, and a survey evaluated CM satisfaction with the EDCMPS. RESULTS: The 2-month preintervention period (July 1, 2022, to August 31, 2022) included 8,677 patients discharged from the ED, with 897 patients (10.3%) identified as at high risk for return based on the previous manual methodology. In the 3-month postintervention period (September 1, 2022, to November 30, 2022), there were 13,566 patients discharged, with 692 patients (5.1%) identified as at high risk for return using the EDCMPS. The EDCMPS outperformed the manual method, yielding a significantly higher odds ratio (OR) for 7- and 30-day ED return or hospitalization (e.g., 30-day any return OR = 4.21 vs. 1.69). The survey showed broad ED CM agreement on the tool's superior performance, especially in organizing outpatient resources and referring to support programs. However, challenges in securing primary care follow-up, housing, and health insurance applications were identified. The tool's collaborative development approach ensured its fit to ED CM needs, contributing to its success. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: The EDCMPS showcases promise in enhancing ED CM efficiency, with strong frontline staff endorsement. It pinpoints areas needing focus for patient support and has the potential to reduce ED revisits and therefore health care utilization. Its methodology offers insights for similar future implementations in health care institutions.

Prognostic value of pre-operative mean corpuscular volume (MCV) in colorectal cancer.

BACKGROUND: Mean corpuscular volume (MCV) has been shown to have some correlation to oncological outcomes in oesophageal cancer, with high pre-operative MCV associated with disease recurrence. A similar association has previously been reported in colorectal cancer. AIMS: This study is aimed at investigating whether high MCV bears similar relation to post-operative outcome and disease recurrence in colorectal cancer (CRC). METHODS: Patients undergoing elective CRC resection with curative intent between January 2008 and December 2019 were identified from our prospective database. Review of patient demographic details, American Society of Anaesthesiologists (ASA) grade, smoking and alcohol intake were performed. In addition, tumour location and staging, operation performed, pre-operative laboratory data and oncological management of each patient were noted. Post-operative morbidity (Clavien-Dindo (CD) score > 2), 30-day mortality, in-hospital mortality and cancer recurrence were examined and multivariable regression analysis was performed to predict these outcomes. RESULTS: A total of 1,293 CRCs were resected, with 1,159 patients (89.7%) experiencing a hospital course without major morbidity (CD < 3). 30-day mortality rate was less than 1% (12/1293). There were 176 patients (13.6%) with recurrence at follow-up. When multivariable regression analysis was performed, high pre-operative MCV did not predict negative post-operative or oncological outcomes. CONCLUSION: MCV does not appear to be an independent prognostic factor for outcomes following elective CRC resection.

Examining the efficacy of verteporfin photo-dynamic therapy (PDT) at different dose & fluence levels.

OBJECTIVES: Photodynamic therapy (PDT) is a vaso-occlusive treatment for a number of chorioretinal vascular pathologies. We aimed to retrospectively analyse efficiency and safety of PDT for different conditions (central serous retinopathy (CSR), age-related macular degeneration (AMD), macular telangiectasia type 2 and choroidal hemangioma) and with different verteporfin parameters. METHODS: Clinical parameters were ascertained from the medical records of patients undergoing PDT over a 6-year period. This included indications for PDT, dosing regimens of verteporfin PDT (which includes treatment dose of verteporfin and fluence). Response to treatment was measured by best corrected visual acuity (BCVA) and central foveal thickness (CFT) on ocular coherence tomography. Complications and side effects were recorded. RESULTS: 67.4 % (31/46) of PDT treatments performed over the last six years were for CSR. In the CSR cohort, there were significant improvements in BCVA (0.47 ± 0.24 to 0.29 ± 0.27, p < 0.05) and CFT (350.2µm ± 66.9 µm to 286.1µm ± 60.6 µm. In the AMD cohort, there was no change in BCVA (1.08 ± 0.52 to 1.07 ± 0.53, p = 0.96) but significant improvement in CFT (488.2µm ± 164.6 µm to 348.7µm ± 65.7 µm, p < 0.05). There was no significant difference in BCVA or CFT for macular telangiectasia type 2 and choroidal hemangioma. CONCLUSIONS: PDT continues to have a role in the management of medical retina conditions. Our results show PDT is most effective in improving and stabilizing visual acuity in CSR, with earlier intervention resulting in better outcomes.

Electronic health record-based readmission risk model performance for patients undergoing outpatient parenteral antibiotic therapy (OPAT).

BACKGROUND: Outpatient Parenteral Antibiotic Therapy (OPAT) provides coordinated services to deliver parenteral antibiotics outside of the acute care setting. However, the reduction in monitoring and supervision may impact the risks of readmission to the hospital. While identifying those at greatest risk of hospital readmission through use of computer decision support systems could aid in its prevention, validation of such tools in this patient population is lacking. OBJECTIVE: The primary aim of this study is to determine the ability of the electronic health record-embedded EPIC Unplanned Readmission Model 1 to predict all-cause 30-day hospital unplanned readmissions in discharged patients receiving OPAT through the Duke University Heath System (DUHS) OPAT program. We then explored the impact of OPAT-specific variables on model performance. METHODS: This retrospective cohort study included patients ≥ 18 years of age discharged to home or skilled nursing facility between July 1, 2019 -February 1, 2020 with OPAT care initiated inpatient and coordinated by the DUHS OPAT program and with at least one Epic readmission score during the index hospitalization. Those with a planned duration of OPAT < 7 days, receiving OPAT administered in a long-term acute care facility (LTAC), or ongoing renal replacement therapy were excluded. The relationship between the primary outcome (unplanned readmission during 30-day post-index discharge) and Epic readmission scores during the index admission (discharge and maximum) was examined using multivariable logistic regression models adjusted for additional predictors. The performance of the models was assessed with the scaled Brier score for overall model performance, the area under the receiver operating characteristics curve (C-index) for discrimination ability, calibration plot for calibration, and Hosmer-Lemeshow goodness-of-fit test for model fit. RESULTS: The models incorporating maximum or discharge Epic readmission scores showed poor discrimination ability (C-index 0.51, 95% CI 0.45 to 0.58 for both models) in predicting 30-day unplanned readmission in the Duke OPAT cohort. Incorporating additional OPAT-specific variables did not improve the discrimination ability (C-index 0.55, 95% CI 0.49 to 0.62 for the max score; 0.56, 95% CI 0.49 to 0.62 for the discharge score). Although models for predicting 30-day unplanned OPAT-related readmission performed slightly better, discrimination ability was still poor (C-index 0.54, 95% CI 0.45 to 0.62 for both models). CONCLUSION: EPIC Unplanned Readmission Model 1 scores were not useful in predicting either all-cause or OPAT-related 30-day unplanned readmission in the DUHS OPAT cohort. Further research is required to assess other predictors that can distinguish patients with higher risks of 30-day unplanned readmission in the DUHS OPAT patients.

Aqueous Photoelectrochemical CO2 Reduction to CO and Methanol over a Silicon Photocathode Functionalized with a Cobalt Phthalocyanine Molecular Catalyst.

We report a precious-metal-free molecular catalyst-based photocathode that is active for aqueous CO2 reduction to CO and methanol. The photoelectrode is composed of cobalt phthalocyanine molecules anchored on graphene oxide which is integrated via a (3-aminopropyl)triethoxysilane linker to p-type silicon protected by a thin film of titanium dioxide. The photocathode reduces CO2 to CO with high selectivity at potentials as mild as 0 V versus the reversible hydrogen electrode (vs RHE). Methanol production is observed at an onset potential of -0.36 V vs RHE, and reaches a peak turnover frequency of 0.18 s-1 . To date, this is the only molecular catalyst-based photoelectrode that is active for the six-electron reduction of CO2 to methanol. This work puts forth a strategy for interfacing molecular catalysts to p-type semiconductors and demonstrates state-of-the-art performance for photoelectrochemical CO2 reduction to CO and methanol.

Uptake of BRCA1/BRCA2 predictive genetic testing in an Irish population is low: a missed opportunity.

INTRODUCTION: Predictive testing for BRCA1 or BRCA2 allows at-risk individuals to engage with appropriate screening and treatment services if a pathogenic mutation is identified. Previous studies have shown uptake of predictive testing to most commonly range between 20% and 40% (Table 2). This represents a missed cancer prevention opportunity. Possible explanations for this low uptake include lack of disclosure of at-risk status to relatives, lack of awareness of cancer genetics services, or patient preference. The goal of the current study was to investigate the uptake of BRCA1 or BRCA2 predictive testing in an Irish population. METHODS: We performed a multicentre, retrospective analysis of 63 pedigrees from two Irish tertiary referral hospitals over a five-year period (2012-2017). Family pedigrees were reviewed to identify at-risk family members eligible for predictive BRCA1 or BRCA2 mutation testing as per international guidelines, and testing rates were determined. RESULTS: A total of 1048 eligible individuals were identified, 318 (30.4%) proceeded to BRCA1 or BRCA2 germline testing including [215 (37.5%) females and 99 males (21.5%)]. Women were significantly more likely to test than men (T = 3.7, p < .0002). Uptake of testing was significant higher amongst first-degree relatives 45% (150/323) compared to 20% (50/258) amongst second degree relatives, and 10 % (33/317) amongst more distant relatives (F = 25.32, p < 0.00001). CONCLUSIONS: Uptake of BRCA1 OR BRCA2 mutation testing in Ireland is suboptimal, particularly amongst Irish males and distant relatives. Further research is needed to identify strategies which may improve uptake within current legal and ethical frameworks.

Patient knowledge, personal experience, and impact of the first wave of the COVD-19 pandemic in an Irish oncology cohort.

BACKGROUND: Oncology patients have had to make many changes to minimise their exposure to COVID-19, causing stress. Despite education, some patients still do not recognise potential COVID symptoms. AIMS: We assessed patient knowledge of COVID, and its impact on their behaviours, concerns, and healthcare experience. METHODS: A 16-page questionnaire was distributed to 120 oncology patients attending the day unit of a tertiary Irish cancer centre for systemic anti-cancer therapy (May/June 2020). The Irish 7-day COVID incidence during this period ranged from 2 to 11 cases/100,000 people. RESULTS: One hundred and one responses were received, 1% had tested positive for COVID, and 31% had undergone testing. Participant insight into their knowledge about COVID and their own behaviour was limited in some cases. Seventy-five percent reported total compliance with restrictions, but many were not fully compliant. Self-reported confidence in knowledge was high, but did not predict demonstrated knowledge. Sixty percent did not recognise two or more symptoms; 40% did not self-identify as high-risk. Patients reported more health-related worry (72%), loneliness (51%), and lower mood (42%) since the pandemic began. Financial toxicity worsened, with increased financial worry (78%), reductions in household income (40%), and increased costs due to lockdown (62%). Use of facemasks introduced new communications barriers for 67% of those with hearing loss. CONCLUSIONS: Despite self-reported confidence in knowledge, some patient's recognition of COVID symptoms and the preventative strategies they should use are not optimal, highlighting the need for further education in this regard. COVID has been a significant stressor for patients and more practical, financial, and psychological supports are needed.

A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland.

In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status. "Mainstreaming" BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101  patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland.

Development of a Community Hospital Medicine Affiliated Inpatient Rotation for Family Medicine Residents-A Collaborative Success.

Background: Hospitalists perform key roles as inpatient educators for family medicine residents. For the past decade, Duke University Family Medicine Residency Program had its inpatient family medicine resident rotation at non-Duke facilities. Objective: The authors describe the steps taken in 2020 to develop an inpatient Duke family medicine rotation at a North Carolina community hospital, Duke Regional Hospital, and provide outcomes data. Methods: Duke Family Medicine Residency and Duke Regional Hospital Medicine collaborated in addressing key issues to develop an inpatient rotation for family medicine residents. Performance metrics of patients cared for by both the family medicine inpatient resident team and internal medicine teams were compared. Resident satisfaction survey results were reviewed. Results: Retrospective cohort evaluation comparing the two inpatient services (internal medicine and family medicine) revealed the family medicine resident inpatient service performed comparatively in length of stay and 30-day readmission rates. Resident evaluation surveys of the family medicine inpatient rotation showed overall satisfaction with learning objectives. Conclusions: This new family medicine inpatient rotation has benefitted all parties. Key quality performance metrics such as LOS and readmissions are comparable to internal medicine, hospitalists have more teaching opportunities, and Duke family medicine has its residents training in a Duke-affiliated community hospital for their core inpatient rotation.

Development of a Novel Coaching Platform to Improve Tackle Technique in Youth Rugby Players: A Proof of Concept.

Rugby union is a field sport that is played at amateur and professional levels by male and female players globally. One of the most prevalent injury risks associated with the sport involves tackle collisions with opposition players. This suggests that a targeted injury reduction strategy could focus on the tackle area in the game. In amateur rugby union, injuries to the head, face and shoulder are the most common injury sites in youth rugby playing populations. A suboptimal tackle technique may contribute to an increased injury risk in these populations. One proposed mitigation strategy to reduce tackle-related injuries in youth populations may be to increase tackle proficiency by coaching an effective tackle technique. The present study aimed to demonstrate a proof of concept for a tackle technique coaching platform using inertial measurement units (IMUs) and a bespoke mobile application developed for a mobile device (i.e., a mobile phone). The test battery provided a proof of concept for the primary objective of modelling the motion of a player in a tackle event. The prototype (bespoke mobile application) modelled the IMU in a 3D space and demonstrated the orientation during a tackle event. The participants simulated ten tackle events that were ten degrees above and ten degrees below the zero degree of approach, and these (unsafe tackles) were indicated by a red light on the mobile display unit. The parameters of ten degrees above and below the zero angle of approach were measured using an inclinometer mobile application. These tackle event simulations provided a real-time stream of data that displayed the angle of tackles on a mobile device. The novel coaching platform could therefore constitute part of an injury reduction strategy for amateur or novice coaches to instruct safer tackle practice in youth rugby playing populations.

The Essentials of Multiomics.

Within the last decade, the science of molecular testing has evolved from single gene and single protein analysis to broad molecular profiling as a standard of care, quickly transitioning from research to practice. Terms such as genomics, transcriptomics, proteomics, circulating omics, and artificial intelligence are now commonplace, and this rapid evolution has left us with a significant knowledge gap within the medical community. In this paper, we attempt to bridge that gap and prepare the physician in oncology for multiomics, a group of technologies that have gone from looming on the horizon to become a clinical reality. The era of multiomics is here, and we must prepare ourselves for this exciting new age of cancer medicine.

Extramural venous invasion (EMVI) in colorectal cancer is associated with increased cancer recurrence and cancer-related death.

INTRODUCTION: Colorectal cancer (CRC) outcomes vary depending on tumour biology, with several features used to predict disease behaviour. Extramural venous invasion (EMVI) is associated with negative outcomes and its presence has been established as an indicator of more aggressive disease in CRC. METHODS: A prospectively maintained database was examined for patients undergoing curative resection for non-metastatic CRC between 2012 and 2018 in a tertiary institution. Clinicopathological factors were compared to assess their impact on recurrence, all-cause mortality and cancer-related death. Kaplan Meier analysis of the association between EMVI and these endpoints was performed, and univariable and multivariable analysis was carried out to establish the relationship of predictive factors in oncological outcomes. RESULTS: Eighty-eight (13.5%) of 654 patients developed recurrence. The mean time to recurrence was 19.8 ± 13.5 months. There were 36 (5.5%) cancer-related deaths at a mean duration of follow-up of 46.3 ± 21.6 months. Two hundred and sixty-six patients had extramural venous invasion (40.7%). EMVI was significantly associated with reduced overall recurrence-free survival, systemic recurrence-free survival, and increased cancer-related death on univariate analysis (p < 0.001 for all, Fig. 1), and multivariable analysis (OR 1.8 and 2.1 respectively, p < 0.05 for both). CONCLUSION: EMVI is associated with a poor prognosis, independent of stage, nodal status and other histopathological features. The presence of EMVI should be strongly considered as an indication for adjuvant therapy.