Using in silico methods to determine optimal tapering regimens for decanoate-based long-acting injectable psychosis drugs.

Background: Reducing the dose of psychosis drugs in a gradual hyperbolic manner may minimise withdrawal effects and risk of relapse. There is presently limited guidance on tapering decanoate-based long-acting injectable dopamine antagonists (LIDAs). Objectives: We aimed to apply hyperbolic principles of tapering to the decanoate-based LIDAs flupentixol, zuclopenthixol and haloperidol to develop withdrawal regimens. Design: We used in silico methodology to predict plasma drug levels and D2 occupancy for different LIDA regimens. Methods: Existing pharmacokinetic and receptor occupancy data from nuclear neuroimaging studies were used to power modelling. Abrupt discontinuation was examined as a potential strategy, and dose reduction was modelled with pre-defined constraints used in similar work of 10 (fast regimens), 5 (moderate) and 2.5 (slow) percentage points of D2 occupancy change per month. Results: Abrupt discontinuation of decanoate-based LIDAs leads to excessive change in D2 occupancy which violated our pre-defined constraints, potentially resulting in withdrawal symptoms and increased risk of relapse. Reduction of LIDA dose allowed hyperbolic reduction in plasma level consistent with imposed constraints on receptor occupancy reduction rate. For equivalent per-weekly LIDA dosing, more frequent administration allowed a more gradual reduction of D2 occupancy. However, switching to oral forms is required to continue hyperbolic tapering to full discontinuation; reduction to zero using only LIDA produces too large a reduction in D2 occupancy. Guidance for reduction and cessation of LIDAs according to slow, moderate and fast criteria is provided. Conclusion: Abrupt cessation of decanoate LIDAs is not consistent with gradual hyperbolic tapering, despite their longer half-lives compared with oral formulations. Reduction to the point of full discontinuation can only be achieved by switching to oral therapy to complete the taper. These results are limited by the in silico and theoretical nature of the study, and there is a need to confirm these findings through real-world observational and interventional studies.

Computer-based research on the best way to reduce the dose and eventually stop three depot antipsychotics What is the problem? Psychosis affects how someone experiences reality. Antipsychotics are used to treat psychosis. They work by blocking a chemical called dopamine. Stopping these too rapidly can cause psychosis to occur again. This might be because the dopamine block is removed suddenly. Sometimes antipsychotics are given by injection. Injections stay in the body for a longer time than tablets. The best way to reduce these injections is currently unknown. What did we do? We explored the best way to reduce and stop antipsychotic injections. We looked at three different types of psychosis injection. We used existing data to assess how these drugs affect the brain. We examined what would happen if an antipsychotic injection was suddenly stopped. We then evaluated the effect of reducing the dose gradually. What did we find? Stopping antipsychotic injections suddenly would lead to rapid changes at brain receptors. This might lead to symptoms of withdrawal and a high risk of psychosis recurring. Reducing the dose of injections leads to less change than stopping suddenly. Switching to a tablet allows for more control when reducing dose. Having injections more often also reduce the changes occurring between injections. We outline three different rates of dose reduction. What does this mean? Antipsychotic injections stay in the body longer than tablets. However, stopping injections suddenly may still not be safe. We recommend that people reduce the dose of their injection instead. We also recommend people switch to tablets or liquid before stopping. It should be noted that our research is computer-based. We would like to see our recommendations tested in the real world.

Airway decision making in major head and neck surgery: Irish multicenter, multidisciplinary recommendations.

Major head and neck surgery poses a threat to perioperative airway patency. Adverse airway events are associated with significant morbidity, potentially leading to hypoxic brain injury and even death. Following a review of the literature, recommendations regarding airway management in head and neck surgery were developed with multicenter, multidisciplinary agreement among all Irish head and neck units. Immediate extubation is appropriate in many cases where there is a low risk of adverse airway events. Where a prolonged definitive airway is required, elective tracheostomy provides increased airway security postoperatively while delayed extubation may be appropriate in select cases to reduce postoperative morbidity. Local institutional protocols should be developed to care for a tracheostomy once inserted. We provide guidance on decision making surrounding airway management at time of head and neck surgery. All decisions should be agreed between the operating, anesthetic, and critical care teams.

The distinct affect regulation functions of body image flexibility and inflexibility: A prospective study in adolescents and emerging adults.

Body image flexibility and inflexibility are alternative ways of responding to body image threats. Affect regulation offers a framework for understanding how these responses impact health outcomes; however, research in young people is limited. This prospective study tested two potential affect regulation functions in adolescents and emerging adults (N = 351, 66.7% female) via online surveys completed five months apart. Specifically, body image flexibility and inflexibility were tested as (a) direct predictors of adaptive (body appreciation, intuitive eating) and maladaptive (muscle-building strategies, disordered eating) outcomes, and (b) moderators of the indirect effect of a social comparison threat via body appreciation. Results from hierarchical linear and conditional process models showed that body image flexibility and inflexibility served distinct affect regulation functions. Whereas body image inflexibility directly predicted adaptive and maladaptive body- and eating-related outcomes, body image flexibility protected against the negative effects of social comparison on intuitive eating via body appreciation. Findings suggest that adolescents and emerging adults could benefit from learning body image flexibility skills and reducing inflexibility to promote positive body image and prevent body- and eating-related disturbances. Future research should investigate how body image flexibility and inflexibility relate to other established threats and outcomes in diverse demographic groups.

Time to ECG diagnosis delays inter-hospital transfer to revascularization in STEMI patients presenting to a regional emergency department: a five-year audit.

BACKGROUND: Reducing the door-to-balloon time (D2BT) in ST-elevation myocardial infarction (STEMI) patients maximizes myocardial salvage and mitigates morbidity/mortality. AIMS: To assess the D2BT in STEMI patients requiring inter-hospital transfer for revascularization and identify any potential causes of delay. METHODS: Consecutive patients presenting to the Connolly Hospital Blanchardstown (CHB) emergency department (ED) who were transferred to the Mater Misericordiae University Hospital in Dublin for primary percutaneous coronary intervention from January 2018 to October 2022 were identified in a regional database and their D2BTs calculated. D2BTs were further sub-categorized into key intervals to identify any potential causes of delay. RESULTS: A total of 90 patients were included for analysis, with a median D2BT of 117.5 min (interquartile range [IQR]: 99.3-170.8 min) and 52.5% of patients achieving the ≤ 120 min target. Despite being the shortest interval considered, the time from arrival at the CHB ED to diagnostic electrocardiogram (ECG) was a substantial contributor to the overall delay to revascularization given its wide variability (median: 18.0 min; IQR: 9.0-46.8 min), with only 28.8% of patients achieving the ≤ 10 min target. CONCLUSIONS: Nearly half of the patients studied failed to achieve the overall target D2BT for revascularization. The time from arrival at the CHB ED to diagnostic ECG was identified as a substantial contributor to this failure, with a median time almost twice that of the target and a quarter of all patients spending longer than 46.8 min. These findings highlight a need to improve the implementation of ECG triage and interpretation in the ED.

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.

A proposal for reducing maximum target doses of drugs for psychosis: Reviewing dose-response literature.

BACKGROUND: Presently, there is limited guidance on the maximal dosing of psychosis drugs that is based on effectiveness rather than safety or toxicity. Current maximum dosing recommendations may far exceed the necessary degree of dopamine D2 receptor blockade required to treat psychosis. This may lead to excess harm through cognitive impairment and side effects. AIMS: This analysis aimed to establish guidance for prescribers by optimally dosing drugs for psychosis based on efficacy and benefit. METHODS: We used data from two dose-response meta-analyses and reviewed seven of the most prescribed drugs for psychosis in the UK. Where data were not available, we used appropriate comparison techniques based on D2 receptor occupancy to extrapolate our recommendations. RESULTS: We found that the likely threshold dose for achieving remission of psychotic symptoms was often significantly below the currently licensed dose for these drugs. We therefore recommend that clinicians are cautious about exceeding our recommended doses. Individual factors, however, should be accounted for. We outline potentially relevant factors including age, ethnicity, sex, smoking status and pharmacogenetics. Additionally, we recommend therapeutic drug monitoring as a tool to determine individual pharmacokinetic variation. CONCLUSIONS: In summary, we propose a new set of maximum target doses for psychosis drugs based on efficacy. Further research through randomised controlled trials should be undertaken to evaluate the effect of reducing doses from current licensing maximums or from doses that are above our recommendations. However, dose reductions should be implemented in a manner that accounts for and reduces the effects of drug withdrawal.

Safety and Effectiveness of the High-Sensitivity Cardiac Troponin HEART Pathway in Patients With Possible Acute Coronary Syndrome.

BACKGROUND: The HEART Pathway (History, Electrocardiogram, Age, Risk factors, Troponin) can be used with high-sensitivity cardiac troponin to risk stratify emergency department patients with possible acute coronary syndrome. However, data on whether a high-sensitivity HEART Pathway (hs-HP) are safe and effective is lacking. METHODS: An interrupted time series study was conducted at 5 North Carolina sites in 26 126 adult emergency department patients being investigated for possible acute coronary syndrome and without ST-segment-elevation myocardial infarction. Patients were accrued into 16-month preimplementation and postimplementation cohorts with a 6-month wash-in phase. Preimplementation (January 2019 to April 2020), the traditional HEART Pathway was used with 0- and 3-hour contemporary troponin measures (Siemens). In the postimplementation period (November 2020 to February 2022), a modified hs-HP was used with 0- and 2-hour high-sensitivity cardiac troponin (Beckman Coulter) measures. The primary safety and effectiveness outcomes were 30-day all-cause death or myocardial infarction and 30-day hospitalizations. These outcomes and early discharge rate (emergency department discharge without stress testing or coronary angiography) were determined from health records and death index data. Outcomes were compared preimplementation versus postimplementation using χ2 tests and multivariable logistic regression to adjust for potential confounders. RESULTS: Preimplementation and postimplementation cohorts included 12 317 and 13 809 patients, respectively, of them 52.7% (13 767/26 126) were female with a median age of 54 years (interquartile range, 42-66). Rates of 30-day death or MI were 6.8% (945/13 809) postimplementation and 7.7% (948/12 317) preimplementation (adjusted odds ratio, 1.00 [95% CI, 0.90-1.11]). hs-HP implementation was associated with 19.9% (95% CI, 18.7%-21.1%) higher early discharges (post versus pre: 63.6% versus 43.7%; adjusted odds ratio, 2.22 [95% CI, 2.10-2.35]). The hs-HP was also associated with 16.1% (95% CI, 14.9%-17.3%) lower 30-day hospitalizations (postimplementation versus preimplementation, 31.4% versus 47.5%; adjusted odds ratio, 0.51 [95% CI, 0.48-0.54]). Among early discharge patients, death or myocardial infarction occurred in 0.5% (41/8780) postimplementation versus 0.4% (22/5383) preimplementation (P=0.61). CONCLUSIONS: hs-HP implementation is associated with increased early discharges without increasing adverse events. These findings support the use of a modified hs-HP to improve chest pain care.

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.

A 12.4-day periodicity in a close binary system after a supernova.

Neutron stars and stellar-mass black holes are the remnants of massive star explosions1. Most massive stars reside in close binary systems2, and the interplay between the companion star and the newly formed compact object has been theoretically explored3, but signatures for binarity or evidence for the formation of a compact object during a supernova explosion are still lacking. Here we report a stripped-envelope supernova, SN 2022jli, which shows 12.4-day periodic undulations during the declining light curve. Narrow Hα emission is detected in late-time spectra with concordant periodic velocity shifts, probably arising from hydrogen gas stripped from a companion and accreted onto the compact remnant. A new Fermi-LAT γ-ray source is temporally and positionally consistent with SN 2022jli. The observed properties of SN 2022jli, including periodic undulations in the optical light curve, coherent Hα emission shifting and evidence for association with a γ-ray source, point to the explosion of a massive star in a binary system leaving behind a bound compact remnant. Mass accretion from the companion star onto the compact object powers the light curve of the supernova and generates the γ-ray emission.

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.

Sex and race differences in the performance of the European Society of Cardiology 0/1-h algorithm with high-sensitivity troponin T.

The diagnostic performance of the high-sensitivity troponin T (hs-cTnT) European Society of Cardiology (ESC) 0/1-h algorithm in sex and race subgroups of US Emergency Department (ED) patients is unclear. A pre-planned subgroup analysis of the STOP-CP cohort study was conducted. Participants with 0- and 1-h hs-cTnT measures from eight US EDs (1/2017 to 9/2018) were stratified into rule-out, observation, and rule-in zones using the hs-cTnT ESC 0/1 algorithm. The primary outcome was adjudicated 30-day cardiac death or MI. The proportion with the primary outcome in each zone was compared between subgroups with Fisher's exact tests. The negative predictive value (NPV) of the ESC 0/1 rule-out zone for 30-day CDMI was calculated and compared between subgroups using Fisher's exact tests. Of the 1422 patients enrolled, 54.2% (770/1422) were male and 58.1% (826/1422) white with a mean age of 57.6 ± 12.8 years. At 30 days, cardiac death or myocardial infarction (MI) occurred in 12.9% (183/1422) of participants. Among patients stratified to the rule-out zone, 30-day cardiac death or MI occurred in 1.1% (5/436) of women versus 2.1% (8/436) of men (p = .40) and 1.2% (4/331) of non-white patients versus 1.8% (9/490) of white patients (p = .58). The NPV for 30-day cardiac death or MI was similar among women versus men (98.9% [95% confidence interval, CI: 97.3-99.6] vs. 97.9% [95% CI: 95.9-99.1]; p = .40) and among white versus non-white patients (98.8% [95% CI: 96.9-99.7] vs. 98.2% [95% CI: 96.5-99.2]; p = .39). NPVs <99% in each subgroup suggest the hs-cTnT ESC 0/1-h algorithm may not be safe for use in US EDs. Trial Registration: High-Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification (STOP-CP; ClinicalTrials.gov: NCT02984436; https://clinicaltrials.gov/ct2/show/NCT02984436).

The role of surgery for anaplastic thyroid carcinoma in the era of targeted therapeutics: A scoping review.

Background: Questions exist regarding patient selection for surgery in anaplastic thyroid carcinoma (ATC), particularly with the advent of neoadjuvant-targeted therapeutics. The present scoping review sought to evaluate what extent of surgical resection should be performed in ATC. Methods: A scoping review was carried out in accordance with Joanna Briggs Institute and the preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) protocols. Included studies were required to provide clear description of the surgery performed for ATC. Results: The final search identified 6901 articles. Ultimately only 15 articles including 1484 patients met inclusion criteria. A total of 765 patients (51.5%) underwent attempted curative intent surgery. The approach to resection of adjacent tissues varied between studies. Eight studies considered laryngeal ± pharyngeal resection (8/15, 53.3%), eight studies (53.3%) considered tracheal resection and again eight studies (53.3%) considered esophageal resection. More extensive resections increased morbidity without improving overall survival (OS) (<9 months in the 12 studies using a combination of surgery and chemoradiotherapy). In the three studies utilizing targeted therapy in addition to surgery, OS was notably improved while surgical resection following neoadjuvant therapy was less extensive. Conclusions: There is no clear agreement in the literature regarding the limits of surgical resection in locoregionally advanced ATC. A definition of surgically resectable disease will be required to guide surgical decision making in ATC, particularly with the potential to reduce tumor burden using neoadjuvant targeted treatment in suitable patients. Level of evidence: III.

Implementing gradual, hyperbolic tapering of long-acting injectable antipsychotics by prolonging the inter-dose interval: an in silico modelling study.

Gradual, hyperbolic tapering has been proposed as a method to reduce the risk of withdrawal effects and potential relapse of an underlying condition by minimising disruption of existing equilibria. We applied hyperbolic tapering principles in silico to long-acting aripiprazole to generate regimens for withdrawal in clinical practice. We derived thresholds for taper rates using existing studies and consensus. Using pharmacokinetic data for aripiprazole long-acting injectable antipsychotic (ALAI), we conducted in silico modelling to examine the impact of abrupt cessation of long-acting injectable antipsychotic (LAI) medication and the effect of prolonging inter-dose interval on plasma aripiprazole levels and consequent D2 occupancy. We also modelled transitions from LAI medication to oral medication. Regimens were designed to afford a rate of reduction between 5 and 12.5 percentage points of D2 occupancy per month. Abrupt discontinuation of ALAI was shown to lead to a maximal D2 occupancy reduction of 16.8 percentage points per month; prolongation of the inter-dose interval of ALAI produced a slower reduction. Specifically, hyperbolic tapering was afforded by prolongation of a 400 mg ALAI inter-dose interval from 4 to 7 weeks, before reducing the dose to 300 mg ALAI. This could then be administered at up to 4-week (for 6% maximal D2 occupancy change), 6-week (9% change) or 7-week (11% change) intervals. Switching to oral medication - 5, 2.5 and 1.25 mg for the three regimens, respectively - is required for ALAI to complete full cessation to prevent too rapid a reduction in D2 occupancy. Oral medication should probably be maintained at a consistent dose for 3-6 months before further reductions to account for residual LAI being concurrently eliminated. Hyperbolic dose tapering is possible with ALAI through prolongation of the inter-dose interval and may reduce the risk of relapse compared to abrupt discontinuation of LAI medication.

Uncovering a population of gravitational lens galaxies with magnified standard candle SN Zwicky.

Detecting gravitationally lensed supernovae is among the biggest challenges in astronomy. It involves a combination of two very rare phenomena: catching the transient signal of a stellar explosion in a distant galaxy and observing it through a nearly perfectly aligned foreground galaxy that deflects light towards the observer. Here we describe how high-cadence optical observations with the Zwicky Transient Facility, with its unparalleled large field of view, led to the detection of a multiply imaged type Ia supernova, SN Zwicky, also known as SN 2022qmx. Magnified nearly 25-fold, the system was found thanks to the standard candle nature of type Ia supernovae. High-spatial-resolution imaging with the Keck telescope resolved four images of the supernova with very small angular separation, corresponding to an Einstein radius of only θE = 0.167″ and almost identical arrival times. The small θE and faintness of the lensing galaxy are very unusual, highlighting the importance of supernovae to fully characterize the properties of galaxy-scale gravitational lenses, including the impact of galaxy substructures.

International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System.

Objectives Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic ( p < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57-0.96, p = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25-1.00, p = 0.036). Conclusions We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

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.

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.

A Rare Complication of Ascariasis: A Case of Acute Interstitial Nephritis.

Acute interstitial nephritis (AIN) due to helminths is a rare cause of acute kidney injury (AKI). Helminthiases often progresses insidiously, making diagnosis difficult. This was the case of a 72-year-old man, who presented with renal failure, itching and diarrhoea. Urinalysis revealed leukocyturia, microhaematuria and mild proteinuria. A full blood count revealed leucocytosis with eosinophilia. A stool parasitological examination revealed fertilised eggs of Ascaris lumbricoides. Tubulointerstitial nephropathy secondary to A. lumbricoides infection was suspected. A percutaneous renal biopsy was not performed since the patient refused the anti-platelet therapy discontinuation. Mebendazole, albendazole and prednisone therapy was administered. After worm eradiation and discharge, recovery from the parasitosis, absence of pruritus and eosinophilia, and progressive improvement of renal function were observed, strongly suggesting a causal relationship between Ascaris infection and AIN. Parasite infection should be considered in the differential diagnosis of unexplained renal failure because early diagnosis and treatment are necessary to avoid irreversible complications.

Evaluation of IL-35, as a Possible Biomarker for Follow-Up after Therapy, in Chronic Human Schistosoma Infection.

The host response to helminth infections is characterized by systemic and tissue-related immune responses that play a crucial role in pathological diseases. Recently, experimental studies have highlighted the role of regulatory T (Tregs) and B (Bregs) cells with secreted cytokines as important markers in anti-schistosomiasis immunity. We investigated the serical levels of five cytokines (TNFα, IFN-γ, IL-4, IL-10 and IL-35) in pre- and post-treatment samples from chronic Schistosoma infected patients to identify potential serological markers during follow-up therapy. Interestingly, we highlighted an increased serum level of IL-35 in the pre-therapy samples (median 439 pg/mL for Schistosoma haematobium and 100.5 pg/mL for Schistsoma mansoni infected patients) compared to a control group (median 62 pg/mL and 58 pg/mL, respectively, p ≤ 0.05), and a significantly lower concentration in post-therapy samples (181 pg/mL for S. haematobium and 49.5 pg/mL for S. mansoni infected patients, p ≤ 0.05). The present study suggests the possible role of IL-35 as a novel serological biomarker in the evaluation of Schistosoma therapy follow-up.

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.