Electrocardiographic predictors of response to sacubitril/valsartan therapy in heart failure with reduced ejection fraction.

BACKGROUND: Sacubitril/valsartan (SV) is currently recommended as a first-line therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to its significant clinical and prognostic benefit; however, not all patients respond to therapy and predictors of clinical response to SV remain under-studied. AIMS: To identify electrocardiographic (ECG) predictors of response to SV therapy in HFrEF patients. METHODS: A retrospective analysis of a hospital heart failure registry was undertaken. Consecutive HFrEF patients (New York Heart Association class II-III) on maximal-dose SV were studied. Response to SV was defined as ≥10% relative improvement in left ventricular ejection fraction (LVEF) at 3-months post-maximal-dose therapy. Pre-therapy ECGs were retrospectively analyzed for axes and standard wave and interval durations. Logistic regression was used to estimate odds ratios and 95% confidence intervals for associations between predictors and therapeutic response. Backward stepwise regression was employed to develop a parsimonious model. RESULTS: P-wave duration (PWD) 100-120 ms, PWD >120 ms, and QTc >460 ms were associated with response to SV on univariate analysis: OR 18.00 (4.45-122.90), 5.00 (1.47-20.42), and 3.10 (1.18-9.22), respectively. The preferred model that included the former two predictors in combination with pre-therapy creatinine, mineralocorticoid receptor antagonist use, and LVEF was highly selective (area under the ROC curve = 0.868). CONCLUSIONS: Prolongation of both PWD and QTc interval on baseline ECG in HFrEF patients is predictive of therapeutic response to maximal-dose SV therapy and may indicate early cardiac remodeling that is highly amenable to reversal.

Epidemiology and management of oral cavity squamous cell carcinoma in Ireland.

INTRODUCTION: The epidemiology and management of oral cavity cancer have changed considerably in recent decades. This study examines epidemiological and management trends in oral cavity squamous cell carcinoma (OCSCC). METHODS: A retrospective cohort study of data from the National Cancer Registry of Ireland between 1994 and 2014. RESULTS: A total of 2725 patients were identified. The most common subsites were the tongue (34 %, n = 1025), lip (19 %, n = 575), floor of mouth (FOM) (18 %, n = 550), and retromolar trigone (RMT) (6 %, n = 189). The incidence of OCSCC remained largely unchanged (3.14 cases/100000/year) during the study period. 5-year disease-specific survival (DSS) was 58.6 % overall, varying between subsites (lip 85 %, RMT 62.9 %, tongue 54.7 %, and FOM 47.3 %). DSS improved over the study period (p = 0.03), in particular for tongue primaries (p = 0.007). Primary surgery significantly improved DSS versus radiotherapy (HR 0.28, p < 0.0001). Survival of T4 disease managed surgically was superior to that of T1 disease managed with radiotherapy. In node positive patients, chemotherapy improved overall survival (HR 0.8 p = 0.038) but not DSS (HR 0.87 p = 0.215). CONCLUSION: Primary surgery remains the standard of care in the management of OCSCC. Prognosis has improved in line with an increase in the use of primary surgery in the same time frame, though the incidence remains unchanged.

Anaplastic thyroid cancer:Improved understanding of what remains a deadly disease.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare, undifferentiated form of thyroid cancer accounting for less that 2 % of thyroid cancers. Here we provide an overview of the contemporary understanding of ATC as well as discussing in detail any pertinent updates in the molecular understanding and treatment of this disease with reference to the 2021 American Thyroid Association (ATA) guidelines. METHODS: A review of the literature regarding the understanding, management and prognosis of ATC was undertaken using both Pubmed and Cochrane databases along with local institutional experience. Studies published in the last 5 years were prioritised for inclusion. RESULTS: Between 80 and 90 % of patients will have disease that has spread beyond the thyroid gland at presentation. Despite the use of aggressive, multimodal, conventional treatment strategies encompassing surgery and chemoradiotherapy, the median overall survival has remained between 3 and 6 months. Our understanding has evolved regarding the key oncogenic mutations involved in the development of ATC. These include BRAF, RAS, PI3K, PTEN, TP53 and TERT mutations. There is growing evidence that novel targeted therapies against these mutations may improve outcomes in this disease which has led to FDA approval of dabrafenib/trametinib combined BRAF/Mek inhibition. CONCLUSIONS: The prognosis of ATC remains dismal. Recent development and approval of targeted therapies offers hope of improved oncologic outcomes with further data eagerly awaited surrounding the impact of these targeted therapies.

Derivation and validation of a high sensitivity troponin-T HEART pathway.

BACKGROUND: The HEART Pathway is widely used for chest pain risk stratification but has yet to be optimized for high sensitivity troponin T (hs-cTnT) assays. METHODS: We conducted a secondary analysis of STOP-CP, a prospective cohort study enrolling adult ED patients with symptoms suggestive of acute coronary syndrome at 8 sites in the United States (US). Patients had a 0- and 1-hour hs-cTnT measured and a HEAR score completed. A derivation set consisting of 729 randomly selected participants was used to derive a hs-cTnT HEART Pathway with rule-out, observation, and rule-in groups for 30-day cardiac death or myocardial infarction (MI). Optimal baseline and 1-hour troponin cutoffs were selected using generalized cross validation to achieve a negative predictive value (NPV) >99% for rule out and positive predictive value (PPV) >60% or maximum Youden index for rule-in. Optimal 0-1-hour delta values were derived using generalized cross validation to maximize the NPV for the rule-out group and PPV for the rule-in group. The hs-cTnT HEART Pathway performance was validated in the remaining cohort (n = 723). RESULTS: Among the 1452 patients, 30-day cardiac death or MI occurred in 12.7% (184/1452). Within the derivation cohort the optimal hs-cTnT HEART Pathway classified 36.5% (266/729) into the rule-out group, yielding a NPV of 99.2% (95% CI: 98.2-100) for 30-day cardiac death or MI. The rule-in group included 15.4% (112/729) with a PPV of 55.4% (95% CI: 46.2-64.6). In the validation cohort, the hs-cTnT HEART Pathway ruled-out 37.6% (272/723), of which 2 had 30-day cardiac death or MI, yielding a NPV of 99.3% (95% CI: 98.3-100). The rule-in group included 14.5% (105/723), yielding a PPV of 57.1% (95% CI: 47.7-66.6). CONCLUSIONS: A novel hs-cTnT HEART Pathway with serial 0- and 1-hour hs-cTnT measures has high NPV and moderate PPV for 30-day cardiac death or MI.

Utility of screening for silent myocardial ischaemia in diabetes with an annual electrocardiogram.

BACKGROUND AND METHODS: Asymptomatic coronary artery disease (CAD) is common in people with diabetes mellitus, but there is a lack of consensus regarding appropriate screening for the condition. We performed a 12-lead electrocardiogram (ECG) on 312 consecutive participants with diabetes mellitus attending for routine annual outpatient review in order to determine the effectiveness of a yearly ECG in screening people with diabetes for asymptomatic CAD. RESULTS: Three of 312 participants (0.96%, 95% CI 0.2%-2.78%) had a newly identified ECG abnormality. One person had newly discovered atrial fibrillation. Two people had abnormalities which prompted further investigation for asymptomatic CAD. One of these participants underwent percutaneous coronary intervention. Seventeen further participants had abnormalities on ECG which had been previously documented, the majority having been present since their diagnosis of diabetes. CONCLUSION: A low positive yield of routine annual ECG in our study does not support its use as a screening tool for asymptomatic CAD in diabetes. Our findings support advice to perform an ECG at diagnosis of diabetes and to repeat only if a person develops relevant symptoms.

Ablation versus anti-arrhythmic therapy for reducing all hospital episodes from recurrent atrial fibrillation: a prospective, randomized, multi-centre, open label trial.

AIMS: There is rising healthcare utilization related to the increasing incidence and prevalence of atrial fibrillation (AF) worldwide. Simplifying therapy and reducing hospital episodes would be a valuable development. The efficacy of a streamlined AF ablation approach was compared to drug therapy and a conventional catheter ablation technique for symptom control in paroxysmal AF. METHODS AND RESULTS: We recruited 321 patients with symptomatic paroxysmal AF to a prospective randomized, multi-centre, open label trial at 13 UK hospitals. Patients were randomized 1:1:1 to cryo-balloon ablation without electrical mapping with patients discharged same day [Ablation Versus Anti-arrhythmic Therapy for Reducing All Hospital Episodes from Recurrent (AVATAR) protocol]; optimization of drug therapy; or cryo-balloon ablation with confirmation of pulmonary vein isolation and overnight hospitalization. The primary endpoint was time to any hospital episode related to treatment for atrial arrhythmia. Secondary endpoints included complications of treatment and quality-of-life measures. The hazard ratio (HR) for a primary endpoint event occurring when comparing AVATAR protocol arm to drug therapy was 0.156 (95% CI, 0.097-0.250; P < 0.0001 by Cox regression). Twenty-three patients (21%) recorded an endpoint event in the AVATAR arm compared to 76 patients (74%) within the drug therapy arm. Comparing AVATAR and conventional ablation arms resulted in a non-significant HR of 1.173 (95% CI, 0.639-2.154; P = 0.61 by Cox regression) with 23 patients (21%) and 19 patients (18%), respectively, recording primary endpoint events (P = 0.61 by log-rank test). CONCLUSION: The AVATAR protocol was superior to drug therapy for avoiding hospital episodes related to AF treatment, but conventional cryoablation was not superior to the AVATAR protocol. This could have wide-ranging implications on how demand for AF symptom control is met. TRIAL REGISTRATION: Clinical Trials Registration: NCT02459574.

Performance of Prehospital Use of Chest Pain Risk Stratification Tools: The RESCUE Study.

BACKGROUND: Emergency medical services (EMS) assesses millions of patients with chest pain each year. However, tools validated to risk stratify patients for acute coronary syndrome (ACS) and pulmonary embolism (PE) have not been translated to the prehospital setting. The objective of this study is to assess the prehospital performance of risk stratification scores for 30-day major adverse cardiac events (MACE) and PE. METHODS: A prospective observational cohort study of patients ≥21 years of age with acute chest pain who were transported by EMS in two North Carolina (NC) counties was conducted from 18 April 2018-2 January 2019. In this convenience sample, paramedics completed HEAR (history, electrocardiogram, age, risk factor), ED Assessment of Chest Pain Score (EDACS), Revised Geneva Score (RGS), and pulmonary embolism rule-out criteria (PERC) assessments on each patient. MACE (all-cause death, myocardial infarction, and revascularization) and PE at 30 days were determined by hospital records and NC Death Index. The positive (+LR) and negative likelihood ratios (-LR) of the risk scores for 30-day MACE and PE were calculated. RESULTS: During the study period, 82.1% (687/837) patients had all four risk score assessments. The cohort was 51.1% (351/687) female, 49.5% (340/687) African American, and had a mean age of 55.0 years (SD 16.0). At 30 days, MACE occurred in 7.4% (51/687), PE occurred in 0.9% (6/687), and the combined outcome occurred in 8.2% (56/687). The HEAR score had a - LR of 0.46 (95% CI 0.27-0.78) and + LR of 1.48 (95% CI 1.26-1.74) for 30-day MACE. EDACS had a - LR of 0.61 (95% CI 0.46-0.81) and + LR of 2.53 (95% CI 1.86-3.46) for 30-day MACE. The PERC score had a - LR of 0 (95% CI 0.0-1.4) and a + LR of 1.38 (95% CI 1.32-1.45) for 30-day PE. The RGS score had a - LR of 0 (95% CI 0.0-0.65) and a + LR of 2.36 (95% CI 2.16-2.57) for 30-day PE. The combination of a low-risk HEAR score and negative PERC evaluation had a - LR of 0.25 (95% CI 0.08-0.76) and a + LR of 1.21 (95% CI 1.21-1.30) for 30-day MACE or PE. CONCLUSION: The combination of a paramedic-obtained HEAR score and PERC evaluation performed best to exclude 30-day MACE and PE but was not sufficient for directing prehospital decision making.

Using Virtual Emergency Medicine Clinicians as a Health System Entry Point (Virtual First): Cross-Sectional Survey Study.

BACKGROUND: The COVID-19 pandemic accelerated the use and acceptance of telemedicine. Simultaneously, emergency departments (EDs) have experienced increased ED boarding. With this acceptance of telemedicine and the weighty increase in patient boarding, we proposed the innovative Virtual First (VF) program to leverage emergency medicine clinicians' (EMCs) ability to triage patients. VF seeks to reduce unnecessary ED visits by connecting patients with EMCs prior to seeking in-person care rather than using traditional ED referral systems. OBJECTIVE: The goal of this study is to investigate how patients' access to EMCs from home via the establishment of VF changed how patients sought care for acute care needs. METHODS: VF is a synchronous virtual video visit at a tertiary care academic hospital. VF was staffed by EMCs and enabled full management of patient complaints or, if necessary, referral to the appropriate level of care. Patients self-selected this service as an alternative to seeking in-person care at a primary care provider, urgent care center, or ED. A postvisit convenience sample survey was collected through a phone SMS text message or email to VF users. This is a cross-sectional survey study. The primary outcome measure is based on responses to the question "How would you have sought care if a VF visit was not available to you?" Secondary outcome measures describe valued aspects and criticisms. Results were analyzed using descriptive statistics. RESULTS: There were 3097 patients seen via VF from July 2021 through May 2022. A total of 176 (5.7%) patients completed the survey. Of these, 87 (49.4%) would have sought care at urgent care centers if VF had not been available. There were 28 (15.9%) patients, 26 (14.8%) patients, and 1 (0.6%) patient that would have sought care at primary care providers, EDs, or other locations, respectively. Interestingly, 34 (19.3%) patients would not have sought care. The most valued aspect of VF was receiving care in the comfort of the home (n=137, 77.8%). For suggested improvements, 58 (33%) patients most commonly included "Nothing" as free text. CONCLUSIONS: VF has the potential to restructure how patients seek medical care by connecting EMCs with patients prior to ED arrival. Without the option of VF, 64.2% (113/177) of patients would have sought care at an acute care facility. VF's innovative employment of EMCs allows for acute care needs to be treated virtually if feasible. If not, EMCs understand the local resources to better direct patients to the appropriate site. This has the potential to substantially decrease patient costs because patients are given the appropriate destination for in-person care, reducing the likelihood of the need for transfer and multiple ED visits.

High frequency and mortality of head and neck malignancy in organ transplant recipients in Ireland - A national cohort study.

BACKGROUND: Solid organ transplant recipients are recognized to carry a high burden of malignancy and frequently this cancer develops in the head and neck region. Furthermore, cancer of the head and neck post-transplant carries a significantly increased mortality. In this study, we aim to conduct a national retrospective cohort study to investigate the impact of head and neck cancer in terms of frequency and mortality in a large group of solid organ transplant recipients over a 20 year time span and compare the mortality in transplant patients to non-transplant patients with head and neck cancer. METHODS: Patients in the Republic of Ireland who underwent solid organ transplantation between 1994 and 2014 who developed post-transplant head and neck malignancy were identified from the records of two prospective, national databases (National Cancer Registry of Ireland (NCRI) and The Irish Transplant Cancer Group database) working in conjunction with each other. Incidence of head and neck malignancy post-transplant was compared with the general population by means of standardised incidence ratios (SIR). Cumulative incidence of all cause and cancer related mortality from head and neck keratinocytic was undertaken by a competing risks analysis. RESULTS: A total of 3346 solid organ transplant recipients were identified, 2382 (71.2 %) kidney, 562 (16.8 %) liver, 214 (6.4 %) cardiac and 188 (5.6 %) lung. During the period of follow up of 428 patients developed head and neck cancer, representing (12.8 %) of the population. 97 % of these patients developed keratinocytic cancers, specifically, of head and neck. The frequency of post-transplant head and neck cancer was related to the duration of immunosuppression with 14 % of patients developing cancer at 10 years and 20 % having developed at least one cancer by 15 years. 12 (3 %) patients developed non-cutaneous head and neck malignancy. 10 (0.3 %) patients died due to head and neck keratinocytic malignancy post-transplant. Competing risk analysis demonstrated that organ transplantation conferred a strong independent effect of death, compared to non-transplant patients with head and neck keratinocytes. This applied specifically for kidney (HR 4.4, 95 % CI 2.5-7.8) and heart transplants (HR 6.5, 95 % CI 2.1-19.9), and overall, across the four transplant categories (P < 0.001). The SIR of developing keratinocyte cancer varied based on primary tumor site, gender, and type of transplant organ. CONCLUSION: Transplant patients demonstrate a particularly high rate of head and neck keratinocyte cancer with a very high rate of associated mortality. Physicians should be cognizant of the increased rate of malignancy in this population and monitor for red flag signs/symptoms.

Survival in an era of organ preservation: an update on laryngeal cancer in Ireland.

BACKGROUND: Laryngeal cancer epidemiology has changed in recent years, with falling incidence observed internationally. Organ preservation therapies have revolutionised management, though some patients may be unsuitable and survival was noted to fall in the 2000s. This study examines trends in laryngeal cancer in Ireland. METHODS: A retrospective cohort study of National Cancer Registry of Ireland data from 1994 to 2014. RESULTS: From a cohort of 2651, glottic disease was most common (62%, n = 1646). Incidence rose to 3.43 cases/100,000/year for 2010-2014. 5-year disease-specific survival (DSS) was 60.6% and did not change significantly over time. Overall survival (OS) for T3 disease managed with primary radiotherapy was similar to primary surgery (HR 0.98, p = 0.9). DSS for T3 disease improved with primary radiotherapy (HR 0.72, p = 0.045). CONCLUSION: Incidence of laryngeal cancer in Ireland rose despite international trends, while survival changed little. Radiotherapy improves DSS for T3 disease but does not improve OS, possibly secondary to poor organ function post-radiotherapy.

Non-conventional laryngeal malignancies: a multicentre review of management and outcomes.

PURPOSE: Non-conventional laryngeal malignancies (NSCC) often have limited published data to guide management despite individual histopathological subtypes often exhibiting heterogeneous behaviour, characteristics, and treatment responses compared to laryngeal squamous cell carcinoma (SCC). This study aimed to compare oncological outcomes with SCC, specifically disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS). Secondary objectives were to compare treatment differences and perform a state of the art review. METHODS: This was a multicentre retrospective cohort study at four tertiary head and neck centres. Survival outcomes between NSCC and SCC patients were analysed with Kaplan-Meier curves and compared by log rank testing. Univariate Cox regression analysis was performed to predict survival by histopathological subgroup, T-stage, N-stage and M-stage. RESULTS: There were no significant differences in 3-year DFS (p = 0.499), DSS (p = 0.329), OS (p = 0.360) or Kaplan Meier survival curves (DSS/OS) between SCC and overall NSCC groups. However, univariate Cox regression analysis identified "rare" histopathologies (mostly small cell carcinoma) to be predictive of less favourable OS (p = 0.035) but this result was not observed for other NSCC histopathological subgroups. N-stage (p = 0.027) and M-stage (p = 0.048) also predicted OS for NSCC malignancies. Significant differences in treatment modalities were identified with treatment of NSCC typically involving surgical resection and SCC often managed non-surgically (e.g., primary radiotherapy). CONCLUSIONS: Although overall NSCC is managed differently compared to SCC, there do not appear to be differences in survival outcomes between these groups. N-stage and M-stage appear to be more predictive of OS than histopathology than many NSCC subtypes.

Future of Biotransformation Science in the Pharmaceutical Industry.

Over the past decades, the number of scientists trained in departments dedicated to traditional medicinal chemistry, biotransformation and/or chemical toxicology have seemingly declined. Yet, there remains a strong demand for such specialized skills in the pharmaceutical industry, particularly within drug metabolism/pharmacokinetics (DMPK) departments. In this position paper, the members of the Biotransformation, Mechanisms, and Pathways Focus Group (BMPFG) steering committee reflect on the diverse roles and responsibilities of scientists trained in the biotransformation field in pharmaceutical companies and contract research organizations. The BMPFG is affiliated with the International Society for the Study of Xenobiotics (ISSX) and was specifically created to promote the exchange of ideas pertaining to topics of current and future interest involving the metabolism of xenobiotics (including drugs). The authors also delve into the relevant education and diverse training skills required to successfully nurture the future cohort of industry biotransformation scientists and guide them toward a rewarding career path. The ability of scientists with a background in biotransformation and organic chemistry to creatively solve complex drug metabolism problems encountered during research and development efforts on both small and large molecular modalities is exemplified in five relevant case studies. Finally, the authors stress the importance and continued commitment to training the next generation of biotransformation scientists who are not only experienced in the metabolism of conventional small molecule therapeutics, but are also equipped to tackle emerging challenges associated with new drug discovery modalities including peptides, protein degraders, and antibodies. SIGNIFICANCE STATEMENT: Biotransformation and mechanistic drug metabolism scientists are critical to advancing chemical entities through discovery and development, yet the number of scientists academically trained for this role is on the decline. This position paper highlights the continuing demand for biotransformation scientists and the necessity of nurturing creative ways to train them and guarantee the future growth of this field.

Is repeat fine needle aspiration required in thyroid nodules with initial benign cytology? Results from a large Irish series.

BACKGROUND : Fine needle aspiration (FNA) cytology is the preferred method for assessing thyroid nodules for malignancy. Concern remains about the rate of false negative results. The primary aim of this study is to investigate the malignancy rate of thyroid nodules initially classified as benign (Thy 2). METHODS: We retrospectively examined 658 nodules in 653 (429 female) patients between January 2013 to December 2017. All FNA biopsies (FNABs) were performed under ultrasound (US) guidance by a radiologist with expertise in thyroid pathology. Nodules were cytologically classified according to the UK Royal College of Pathologists guidelines. Decisions about further management were made at a regular thyroid multidisciplinary meeting. Follow up of the Thy 2 nodules was determined based on clinical and radiological criteria. RESULTS: The mean age (± SD) was 53.2 (14.6) years. Five hundred out of 658 (76.0%) nodules were classified as Thy 2 (benign) after the first FNAB. Of these thyroid nodules initially classified as benign, 208 (41.6%) underwent repeat FNAB and 9 (1.8%) were surgically removed without repeat FNAB. The remainder were followed up clinically and/or radiologically. Seven (1.4%) of nodules initially classified as Thy 2 were later shown to be or to harbor malignancy after a follow-up of 74.5 (± 19.7) months. Papillary thyroid microcarcinomas were found co-incidentally in two thyroid glands of benign nodules, giving a true prevalence of 5/500 (1.0%). CONCLUSIONS: With a well targeted FNAB, the false negative rate of an initial benign thyroid FNA is very low thus routine second FNAB is not required in patients with a thyroid nodule initially deemed benign. Multidisciplinary input is imperative in informing decision making.

Prehospital Comparison of the HEAR and HE-MACS Scores for 30-Day Adverse Cardiac Events.

OBJECTIVE: The History, Electrocardiogram (ECG), Age, and Risk factor (HEAR) and History and ECG-only Manchester Acute Coronary Syndromes (HE-MACS) risk scores can risk stratify chest pain patients without troponin measures. The objective of this study was to determine if either risk score could achieve the ≥99% negative predictive value (NPV) required to rule out major adverse cardiovascular events (MACE; a composite of all-cause death, myocardial infarction, or coronary revascularization) at 30 days or the ≥50% positive predictive value (PPV) indicative of a patient possibly needing interventional cardiology. METHODS: We performed a pre-planned secondary analysis of the prospective multisite PARAHEART (n = 462, 12/2016-1/2018) and RESCUE (n = 767, 4/2018-1/2019) trials, which accrued adults ≥21 years old with acute non-traumatic chest pain transported by emergency medical services (EMS). Paramedics prospectively completed risk assessment forms. Very low risk was defined by a HEAR score of 0-1 or HE-MACS probability <4%. The primary outcome was 30-day MACE, which was determined by adjudication (PARAHEART) or electronic record review (RESCUE). NPV and PPV with exact 95% confidence intervals (95%CI) for 30-day MACE were calculated for each risk score and compared using McNemar's tests. RESULTS: Among the PARAHEART and RESCUE cohorts, 30-day MACE occurred in 18.8% (87/462) and 6.9% (53/767) of patients, respectively. In PARAHEART, 7.8% (36/462) were very low risk by HEAR score vs. 7.8% (36/462) by HE-MACS (p = 1.0). The HEAR score had a NPV of 97.2% (95%CI 91.9-100.0) vs. 91.7% (95%CI 82.6-100.0) for HE-MACS (p = 0.15). The HEAR and HE-MACS PPVs were similar [46.4% (95%CI 28.0-64.9) vs. 33.3% (95%CI 13.2-53.5) (p = 0.26)]. In RESCUE, the HEAR score identified 14.2% (109/767) as low risk compared to 8.3% (64/767) by HE-MACS (p < 0.001). In this cohort, the HEAR and HE-MACS scores had similar NPVs [98.2% (95%CI 95.7-100.0) vs. 98.4% (95%CI 95.4-100.0) (p = 0.89)] and PPVs [16.2% (95%CI 6.2-32.0) vs. 22.6% (95%CI 12.3-36.2) (p = 0.41)]. CONCLUSIONS: In two prehospital chest pain cohorts, neither the HEAR score nor HE-MACS achieved sufficient NPV or PPV to rule out or rule in 30-day MACE.

The changing face of Irish head and neck cancer epidemiology: 20 years of data.

BACKGROUND: Head and neck cancer (HNC) is associated with significant morbidity and mortality, especially when high stage disease is present. The epidemiology and prognosis of HNC has changed considerably over the last 20 years. AIMS: This study aimed to examine the epidemiological trends in HNC patients over a prolonged period in Ireland. METHODS: We conducted a retrospective cohort study using 20 years of cancer registry data provided by the National Cancer Registry of Ireland. Baseline characteristics and survival statistics were thereby generated. RESULTS: 10,148 patients were identified. There is a growing population of young (< 50 years) and very old (> 85 years) HNC patients; 48.15% of the population was elderly (> 65 years). Oral cavity (29.8%) and laryngeal cancer (28.1%) remain the most prevalent subsites, though oral cavity cancer prevalence declined from 35.9% in 1994 to 27.5% in 2014. Oropharyngeal cancer prevalence increased from 13.6 to 22.2% over the same period. Overall 5-year survival has improved significantly to 56.8% in 2010 but there remains a disparity between the elderly and adult cohorts (42.0% vs 60.7%). 5-year survival for hypopharyngeal and oropharyngeal cancers has improved from 11.8% and 33.3% to 22.2% and 44.8%, respectively, while laryngeal and oral cavity cancer survival remains approximately stable at 58.7% and 61.5%, respectively. CONCLUSION: HNC survival in Ireland has improved in line with increasing recognition of the value of multidisciplinary assessment, subspecialisation in cancer care, and targeted therapies based on tumour subsites. Survival in the elderly cohort remains poor despite increasing recognition of the challenges such cases pose.

Scoring systems for the triage and assessment of short-term cardiovascular risk in patients with acute chest pain.

Acute chest pain is a common emergency department (ED) chief complaint. Evaluating patients for acute coronary syndrome is challenging because missing the diagnosis carries substantial morbidity, mortality, and medicolegal consequences. However, over-testing is associated with increased cost, overcrowding, and possible iatrogenic harm. Over the past two decades, multiple risk scoring systems have been developed to help emergency providers evaluate patients with acute chest pain. The ideal risk score balances safety by achieving high sensitivity and negative predictive value for major adverse cardiovascular events while also being effective in identifying a large proportion of patients for early discharge from the ED. This review examines contemporary risk scores used to risk stratify patients with acute chest pain.

Assessing the quality of life of head and neck healthcare workers during the COVID-19 pandemic-A self-reported global cross-sectional questionnaire study by the International Federation of Head and Neck Oncologic Societies.

BACKGROUND: Considering the pandemic's mode of transmission, the impact on quality of life (QOL) is likely to be exaggerated among healthcare workers (HCWs) who treat head and neck diseases (hHCWs). METHODS: A cross-sectional self-reported QOL assessment was undertaken between July and September 2020 using the World Health Organization Quality of Life instrument sent out to hHCWs. Factors that predicted a poorer QOL were identified using regression models and mediation analysis. RESULTS: Responses from 979 individuals across 53 countries were analyzed with 62.4% participation from low- and middle-income countries. The physical domain had the highest mean scores of 15 ± 2.51, while the environmental domain was the lowest (14.17 ± 2.42). Participants from low- and middle-income countries had a significantly worse physical (p < 0.001) and environmental (p < 0.001) domains, while a low coronavirus disease 2019-related mortality significantly impacted the environmental domain (p-0.034). CONCLUSION: QOL-related issues among hHCWs are a vexing problem and need intervention at an individual and systems level in all parts of the world.

The Royal College of surgeons multidisciplinary guidelines on elective tracheostomy insertion in COVID-19 ventilated patients.

BACKGROUND: The current COVID-19 pandemic has placed enormous strain on healthcare systems worldwide. Understanding of COVID-19 is rapidly evolving. Pneumonia associated with COVID-19 may lead to respiratory failure requiring mechanical ventilation. The rise in patients requiring mechanical ventilation may lead to an increase in tracheostomies being performed in patients with COVID-19. Performing tracheostomy in patients with active SARS-CoV-2 infection poses a number of challenges. METHODS: These guidelines were written following multidisciplinary agreement between Otolaryngology, Head and Neck Surgery, Respiratory Medicine and the Department of Anaesthetics and Critical Care Medicine in the Royal College of Surgeons in Ireland. A literature review was performed and a guideline for elective tracheostomy insertion in patients with COVID-19 proposed. CONCLUSION: The decision to perform tracheostomy in patients with COVID-19 should be undertaken by senior members of the multidisciplinary team. Steps should be taken to minimise risks to healthcare workers.

Academic Partnerships in Global Surgery: An Overview American Surgical Association Working Group on Academic Global Surgery.

: Most surgeons from high-income countries who work in global surgery will do so through partnerships between their institutions and institutions in low- and middle-income countries (LMICs). In this article, the American Surgical Association Working Group for Global Surgery lays out recommendations for criteria that contribute to equitable, sustainable, and effective partnerships. These include ethically engaging with the LMIC partner institution by putting its interests first and by proactively seeking to be aware of cultural issues. Formally structuring the partnership with a memorandum of understanding and clearly designating leaders at both institutions are important criteria for assuring long-term sustainability. Needs assessments can be done using existing methods, such as those established for development of national surgical, obstetric, and anesthesia plans. Such assessments help to identify opportunities for partnerships to be most effective in addressing the biggest surgical needs in the LMIC. Examples of successful high-income countries-LMIC partnerships are provided.

Cancer survival in kidney transplant recipients in Ireland.

BACKGROUND: Transplantation is a well-known risk factor for malignancy. However, outcomes of cancer in transplant recipients compared with non-transplant recipients are less well studied. We aim to study the survival in kidney transplant recipients who develop cancer and compare this with cancer outcomes in the general population. METHODS: We linked data from the National Cancer Registry Ireland with the National Kidney Transplant Database. The period of observation was from 1 January 1994 until 31 December 2014. Transplant recipients were considered at risk from the time of diagnosing cancer. We administratively censored data at 10 years post-cancer diagnosis. Survival was compared with all patients in the general population that had a recorded diagnosis of cancer. RESULTS: There were 907 renal transplant recipients and 426679 individuals in the general population diagnosed with cancer between 1 January 1994 and 31 December 2014. In those with non-melanoma skin cancer, the hazard ratio (HR) for 10-year, all-cause mortality [HR = 3.06, 95% confidence interval (CI) 2.66-3.52] and cancer-specific mortality (HR = 3.91, 95% CI 2.57-5.96) was significantly higher among transplant recipients than the general population. Patients who developed non-Hodgkin lymphoma (HR = 2.89, 95% CI 1.96-4.25) and prostate cancer (HR = 4.32, 95% CI 2.39-7.82) had increased all-cause but not cancer-specific mortality. Colorectal, lung, breast and renal cell cancer did not show an increased risk of death in transplant recipients. CONCLUSION: Cancer-attributable mortality is higher in kidney transplant recipients with non-melanoma skin cancer compared with non-transplant patients. The American Joint Committee on Cancer staging should reflect the increased hazard of death in these immunosuppressed patients.