Clinical Outcomes in Patients with CKD and Rapid or Non-rapid eGFR Decline: A Report from the DISCOVER CKD Retrospective Cohort.

INTRODUCTION: This analysis examined the baseline characteristics and clinical outcomes of patients with chronic kidney disease (CKD) and rapid or non-rapid estimated glomerular filtration rate (eGFR) decline, using retrospective data from DISCOVER CKD (ClinicalTrials.gov, NCT04034992). METHODS: Data (2008-2020) were extracted from UK Clinical Practice Research Datalink, US TriNetX, US Limited Claims and Electronic Health Record Dataset, and Japan Medical Data Vision. Patients with CKD (two consecutive eGFR measures < 75 mL/min/1.73 m2 recorded 90-730 days apart) were included. Rapid eGFR decline was defined as an annual decline of > 4 mL/min/1.73 m2 at 2 years post-index; non-rapid eGFR decline was defined as an annual decline of ≤ 4 mL/min/1.73 m2. Clinical outcomes assessed included all-cause mortality, kidney outcomes (composite risk of kidney failure [progression to CKD stage 5] or > 50% eGFR decline, and kidney failure alone), cardiovascular events-including major adverse cardiovascular events (MACE; non-fatal myocardial infarction/stroke and cardiovascular death)-and all-cause hospitalization. RESULTS: Across databases, rapid eGFR decline occurred in 13.7% of 804,237 eligible patients. Mean annual eGFR decline ranged between - 6.21 and - 6.86 mL/min/1.73 m2 in patients with rapid eGFR decline versus between - 0.11 and - 0.77 mL/min/1.73 m2 in patients with non-rapid eGFR decline. Rapid eGFR decline was associated with increased comorbidity burden and medication prescriptions. Across databases, the composite risk of kidney failure or > 50% decline in eGFR was significantly greater in patients with rapid versus non-rapid eGFR decline (P < 0.01); all-cause mortality, kidney failure alone, MACE, and all-cause hospitalization each significantly increased in two databases (P < 0.01-0.05). CONCLUSION: Understanding patient factors associated with rapid eGFR decline in patients with CKD may help identify individuals who would benefit from proactive management to minimize the risk of adverse outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04034992.

Role of 18F-FDG PET/CT in the management of head and neck cancer patients with persistent cervical lymphadenopathy following chemoradiation.

BACKGROUND: We aim to describe the management and outcomes of patients with persistent lymphadenopathy (LAD) after primary chemoradiation for head and neck squamous cell carcinoma (HNSCC) based on post-treatment PET/CT results. METHODS: Retrospective chart review was conducted of all patients who underwent primary concurrent chemoradiation for HNSCC at a tertiary care center from 2010 to 2022 and had persistent post-treatment LAD. RESULTS: Nearly 62% of patients were managed conservatively, and 27.0% underwent neck dissection. PET-positive patients were more likely to undergo neck dissection than PET-negative patients (p = 0.042). Positive predictive value (PPV) and negative predictive values (NPV) of PET/CT in detecting residual disease in the neck were 48.0% and 73.7%, respectively. CONCLUSIONS: PPV and NPV of PET/CT for detecting residual neck disease in patients with post-treatment LAD was lower than those of HNSCC patients with and without persistent LAD reported in other studies.

Projecting the clinical burden of chronic kidney disease at the patient level (Inside CKD): a microsimulation modelling study.

Background: Chronic kidney disease (CKD) is a global concern that presents significant challenges for disease management. Several factors drive CKD prevalence, including primary risk factors, such as type 2 diabetes and hypertension, and an ageing population. Inside CKD is an international initiative that aims to raise awareness of the substantial burden incurred by CKD. Methods: Using a peer-reviewed microsimulation method, the clinical burden of CKD was estimated from 2022 to 2027. Demographic data from the Americas, Europe, and Asia-Pacific/Middle East were used to generate virtual populations and to project the prevalence of CKD, kidney replacement therapy, associated cardiovascular complications, comorbid conditions, and all-cause mortality in the CKD population over the modelled time frame. Findings: Across the 31 participating countries/regions, the total prevalence of CKD was projected to rise to 436.6 million cases by 2027 (an increase of 5.8% from 2022), with most cases (∼80%) undiagnosed. Inside CKD projected a mean of 8859 cases of heart failure, 10,244 of myocardial infarction, and 7797 of stroke per 100,000 patients with CKD by 2027. Interpretation: The clinical impact of CKD is substantial and likely to increase; the high prevalence of undiagnosed cases and associated complications may benefit from the implementation of health policy interventions that promote screening, earlier diagnosis, and interventions to improve outcomes. Funding: AstraZeneca.

Benefits of Neurosurgical Teleconsults in the Management of Intracerebral Hemorrhage: Transfers and Transportation Cost Reduction.

BACKGROUND: Our study explores the efficacy and economic benefits of neurosurgical teleconsultations in managing intracerebral hemorrhage (ICH), focusing on reducing unnecessary patient transfers and associated costs. METHODS: We conducted a cost-savings analysis at our institution of a previously published pilot study involving a cohort of patients with ICH who were potential candidates for airlift to our tertiary care center but instead received neurosurgical consultation via teleconsultation to avoid the transfer. Data on patient demographics, distances, and costs were collected and analyzed to assess the economic impact of teleconsultations. RESULTS: The cohort comprised 14 patients; we noted significant cost savings from avoiding interhospital transfers, ranging from $84,346.52 to $120,495.03 per patient. Teleconsultations facilitated immediate, collaborative decision-making between healthcare providers at community hospitals and a tertiary care center, reducing the need for expensive air transportation and unnecessary hospital transfers. CONCLUSIONS: Neurosurgical teleconsultations offer a cost-effective alternative to traditional patient transfer methods for ICH management, providing substantial economic benefits while maintaining high physician and patient-family satisfaction levels. This study underscores the potential of our teleneurosurgery program to significantly reduce costs by reducing unnecessary financial burdens on patients' families and healthcare systems.

A Reproducible Peritonsillar Abscess Incision and Drainage Model for Junior Trainees.

OBJECTIVES: To describe the design and construction of a reproducible, low-cost, peritonsillar abscess (PTA) incision and drainage simulator and assess its impact on trainees' confidence. METHODS: The 2-part simulator we developed consisted of a manikin head with a fixed, partially open mouth and a modular PTA mold. The mold is created by injecting a lotion and water mixture into plastic bubbles, followed by silicone solidification. Neodymium magnets secure the silicone-abscess packet to the manikin's palate. The simulator was utilized during an academic otolaryngology residency training program Annual Otolaryngology Boot Camp. A self-assessment Likert scale questionnaire was used to evaluate participants' confidence before and after simulator training. Fourth-year medical students and junior (first and second year) residents who participated in the boot camp and agreed to complete the evaluation were included. RESULTS: Three medical students, 17 PGY-1, and 10 PGY-2 residents agreed to complete the evaluation. All trainees agreed the model was useful for learning skills. The overall post-training confidence Likert scores of participants, and PGY-1 residents in particular, significantly improved compared to their pre-training scores (P < .001). CONCLUSIONS: Our model offers an affordable and efficient training opportunity for residents to enhance their competence in managing PTAs. This approach, with its simple yet effective design and low production cost, shows potential for scalability on a broader scale.

Diversity of US participants in AstraZeneca-sponsored clinical trials.

BACKGROUND: To develop medicines that are safe and efficacious to all patients, clinical trials must enroll appropriate target populations, but imbalances related to race, ethnicity and sex have been reported. A comprehensive analysis and improvement in understanding representativeness of patient enrollment in industry-sponsored trials are key public health needs. METHODS: We assessed race/ethnicity and sex representation in AstraZeneca (AZ)-sponsored clinical trials in the United States (US) from 2010 to 2022, compared with the 2019 US Census. RESULTS: In total, 246 trials representing 95,372 patients with complete race/ethnicity and sex records were analyzed. The proportions of different race/ethnicity subgroups in AZ-sponsored clinical trials and the US Census were similar (White: 69.5% vs 60.1%, Black or African American: 13.3% vs 12.5%, Asian: 1.8% vs 5.8%, Hispanic: 14.4% vs 18.5%). We also observed parity in the proportions of males and females between AZ clinical trials and US Census (males: 52.4% vs 49.2%, females: 47.6% vs 50.8%). Comparisons of four distinct therapy areas within AZ (Respiratory and Immunology [R&I]; Cardiovascular, Renal, and Metabolism [CVRM]; Solid Tumors; and Hematological Malignancies), including by trial phases, revealed greater variability, with proportions observed above and below US Census levels. CONCLUSION: This analysis provides the first detailed insights into the representativeness of AZ trials. Overall, the proportions of different race/ethnicity and sex subgroups in AZ-sponsored clinical trials were broadly aligned with the US Census. We outline some of AZ's planned health equity initiatives that are intended to continue to improve equitable patient enrollment.

Development of hypothyroidism following hemithyroidectomy: A population-based study.

PURPOSE: Hypothyroidism is a known possibility after hemithyroidectomy, with a highly variable incidence in the literature ranging from 8 to 60 %. Incidence of hypothyroidism after hemithyroidectomy was evaluated with a secondary aim to assess incidence in patients with Hashimoto's disease. MATERIALS & METHODS: A retrospective study using the TriNetX global federated research network was performed. We included patients within the last 15 years that were ≥18 years of age and had Current Procedural Terminology codes for hemithyroidectomy. Patients were excluded if they had a total or completion thyroidectomy at any time, a history of thyroid cancer, were preoperatively either on levothyroxine, diagnosed with hypothyroidism, or had a Thyroid Stimulating Hormone ≥ 4 m[IU]/L. We assessed the 3 month incidence of hypothyroidism postoperatively based on the International Classification of Diseases code, TSH ≥ 4 m[IU]/L, or taking levothyroxine after surgery. RESULTS: 6845 patients met the inclusion criteria. Most of the cohort was female (67 %) and white (63 %). The mean age at surgery for this population was 54 ± 14.8 years. During the 15 years of data, we found the 3-month incidence of hypothyroidism following hemithyroidectomy to be 23.58 %. The median time to develop the disease was 41.8 months. A subgroup analysis of those with Hashimoto's revealed a 3-month incidence of 31.1 % of patients developing hypothyroidism after surgery. CONCLUSIONS: This population-based study gives additional insight into the incidence of hypothyroidism after hemithyroidectomy. This will help improve perioperative patient counseling and management.

The Development of Head and Neck Cancer in Patients with the Isolated Complaint of Globus Pharyngeus.

OBJECTIVES: Globus pharyngeus (GP) is a perplexing problem that accounts for 4% of referrals to otolaryngologists. Workup can be extensive and may not be definitive in terms of etiology. The concern that lingers is that of a subtle cancer, which can prolong anxiety and increase testing cost. The aim of this study was to identify the incidence of head and neck cancer (HNC) in patients diagnosed with GP. METHODS: Longitudinal data were captured from two academic institutions, identifying patients with a new diagnosis of globus pharyngeus in 2015. The patient cohort was tracked for at least 4 years to assure follow-up and ability to determine if a HNC developed. Additional demographic data was also collected to determine most common consults, treatments, and testing employed. RESULTS: Excluding patients with previous diagnosis of HNC, 377 patients were identified who presented with GP in 2015 that had at least 4 years of follow-up. Demographics were predominantly women (64.65%), with a mean age of 56.48 years at diagnosis, and the most common provider specialty on the first visit was otolaryngology (39.52%). Four patients ultimately developed HN cancer, for an overall incidence of 1% for the 4-year period of 2015-2019. CONCLUSIONS: Given the long-term follow-up of this population, the overall incidence of developing a head and neck cancer, with a presenting symptom of globus, is low. This is the largest study to date to report the percentage of patients endorsing GP to then subsequently develop HNC. This helps otolaryngologists to reassure patients who have a normal comprehensive exam, flexible endoscopy, and targeted studies. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1147-1154, 2024.

Bell's Palsy and COVID-19: Insights from a Population-Based Analysis.

Background: Coronavirus disease 2019 (COVID-19) has been linked to Bell's palsy and facial paralysis. Studies have also shown increased risk of Bell's palsy in unvaccinated COVID-19 patients. Objective: To compare the relationship between Bell's palsy and COVID-19 infection and vaccination. Design: This is a retrospective longitudinal study. Methods: The COVID-19 research network was used to identify patients with facial palsy presenting to 70 health care organizations in the United States. The incidence of Bell's palsy was measured within an 8-week window after COVID-19 test or vaccination event in identified patients. Results: Incidence of facial palsy diagnosis (0.99%) was higher than the background rate within 2 months of COVID-19 infection. When compared with their negative counterparts, patients with COVID-19 infection had significantly higher risk of Bell's palsy (risk ratio [RR] = 1.77, p < 0.01) and facial weakness (RR = 2.28, p < 0.01). Risk ratio was also amplified when evaluating Bell's palsy (RR = 12.57, p < 0.01) and facial palsy (RR = 44.43; p < 0.01) in COVID-19-infected patients against patients who received COVID-19 vaccination. Conclusion: In our patient population, there is a higher risk of developing facial palsy within 2 months of COVID-19 infection versus vaccination. Vaccinated patients are not at higher risk of developing facial palsy.

Comparison of the incidence of smell and taste disorders between influenza and COVID-19.

OBJECTIVE: Smell and taste disorders among patients with COVID-19 has become increasingly reported in the literature, however the prevalence varies. Post-infectious respiratory dysfunction has also been linked to influenza. In this study, we aimed to compare the rates of smell and taste disorders between COVID-19 and Influenza in unvaccinated patients. STUDY DESIGN: Retrospective cohort study. SETTING: TriNetX research network. METHODS: Two queries were made on 7/1/2023 to include Influenza without a diagnosis of COVID-19 and a COVID-19 without a diagnosis of Influenza. The queries included patients from January 1 to December 31, 2022 from 102 Healthcare Organizations. The resultant population of patients with ICD-10 codes for COVID-19 and Influenza were matched using demographic characteristics to evaluate the risk of smell disorders. RESULTS: The overall 3-month incidence of smell and taste disorders was 0.73 % in the COVID-19 population and 0.1 % in the influenza population. The 3-month matched risk ratios were 11.1 [95 % CI (8.8,13.8)]; p < 0.001) times higher for disorders of the smell and taste secondary to COVID-19 compared to influenza. CONCLUSIONS: Disorders of the smell and taste are more common among patients with COVID-19 compared to patients with Influenza. Beyond smell loss, patients experience additional nasal and sinus-related rhinological symptoms, pointing to COVID-19's and influenza's wider impact on overall rhinological health. We believe that due to the transient nature of these disorders, they might go underreported.

Un reto biomédico: facilitar la disponibilidad informativa acerca de la relación entre la microbiota intestinal, medicamentos y vacunas / A biomedical challenge: to facilitate the availability of information about the relationship between gut microbiota, drugs and vaccines / Um desafio biomédico: facilitar a disponibilidade de informações sobre a relação entre a microbiota intestinal, medicamentos e vacinas

Resumen El personal biomédico carece de plataformas informatizadas que resuman los principales mecanismos de colaboración entre los microbios intestinales y los seres humanos en cuanto a la absorción y transformación de los medicamentos o vacunas y sus respuestas homeostáticas. Por esta razón, el presente trabajo tiene como objetivo aportar evidencias y recomendaciones para el diseño de una plataforma de consulta biomédica, referente a esta relación, lo cual permitirá la valoración de la posible inclusión de la taxa y abundancia microbiana intestinal en los protocolos de evaluación de la efectividad de los mismos. La encuesta realizada a un grupo de profesionales, destinada a la verificación de las posibilidades de acceso y especificidad de este tipo de información posibilitó la identificación de los tópicos principales para la conexión entre grupos de medicamentos, estructura tridimensional, moduladores y mediadores de la respuesta homeostática, biomarcadores, relación inter-reinos y mecanismos patogénicos, de manera que se fusione toda la información "ómica" humanomicrobiota en una plataforma dentro de la página del NCBI, la cual se propone que se denomine Pharmacolobiomic o Pharmaco-metagenomic. La información existe en las bases de datos contenidas en NCBI-NIH, según la búsqueda realizada y el filtrado a partir de 28 628 referencias. A partir de la presente propuesta se demostró la necesidad de contar con una plataformafarma cometagenómica que resuma el papel de la microbiota intestinal en el metabolismo y la efectividad de los fármacos y vacunas; así como disponer de la actualización sistemática para los profesionales en cuanto a la microbiota como biomarcador, en los protocolos de ensayos clínicos.

Abstract Biomedical staff lacks a computer platform that summarises the main mechanisms of collaboration between intestinal microbes and humans, related to the absorption and transformation of drugs and vaccines and their ho-meostatic responses. For this reason, the aim of this work is to provide some evidences and recommendations for the design of a biomedical consultation platform, about the relationship between the microbiota and the effect of drugs or vaccines. These evidences will support the assessment for inclu¬sion of taxa and gut microbial abundance, as a part of clinical protocols of effectiveness. The survey carried out on a group of biomedical professionals, aimed at verifying the possibilities of access and specificity of this type of information made it possible to identify the main topics for the connection between drug groups, three-dimensional structure, modulators and mediators of the homeostatic response, biomarkers, inter-kingdom relationship and pathogenic mechanismsin such a way that all the human-microbiota "omics" information will be shown into a sub-platform within NCBI-NIH, which could be called Pharmacolobiomic or Pharmaco-metagenomic. The information is present in the databases contained in the NCBI, taking into account this search and filtering, from 28 628 references. Based on this proposal, the need for a pharmacometagenomic platform that summarises the role of the intestinal microbiota in the metabolism and effectiveness of drugs and vaccines was demonstrated, as well as having the systematic update for professionals about the microbiota as a biomarker, in clinical trial protocols.

Resumo O pessoal biomédico carece de plataformas computadorizadas que resumam os principais mecanismosde colaboração entre micróbios intestinais e seres humanos, em termos de absorção e transformação demedicamentos e vacinas e suas respostas homeostáticas. Por essa razão, este trabalho visa fornecer evidênciase recomendações para o desenho de uma plataforma de consulta biomédica, referente a esta relação;o que permitirá avaliar a possível inclusão dos táxons e da abundância microbiana intestinal nosprotocolos de avaliação da sua eficácia. A pesquisa realizada em um grupo de profissionais, teve comoobjetivo verificar as possibilidades de acesso e especificidade desse tipo de informação; possibilitouidentificar os principais tópicos para a conexão entre grupos de medicamentos, estrutura tridimensional,moduladores e mediadores da resposta homeostática, biomarcadores, relação inter-reino, mecanismospatogênicos; de forma tal que toda a informação "ômica" humano-microbiota se funde em uma plataformadentro da página do NCBI, à qual se propõe ser chamada de Pharmacolobiomic ou Pharmacometagenomic. A informação existe nas bases de dados contidas em NCBI-NIH, tendo em conta a pesquisarealizada e a filtragem, a partir de 28 628 referências. Com base nessa proposta, foi demonstradaa necessidade de contar com uma plataforma farmacometagenômica que resuma o papel da microbiotaintestinal no metabolismo e eficácia de medicamentos e vacinas; além de ter a atualização sistemáticapara os profissionais quanto à microbiota como biomarcador, nos protocolos de ensaios clínicos.

A Systematic Review of Peritonsillar Abscess Simulators: Enhancing Training and Identifying the Need for Standardization.

OBJECTIVES: To systematically review the literature regarding previously described peritonsillar abscess (PTA) drainage simulation. DATA SOURCES: PubMed, Scopus, Web of Science, Ovid, and Cochrane. REVIEW METHODS: A search of the abovementioned databases was performed in August 2022 using the terms "peritonsillar abscess/quinsy," "incision/drainage/aspiration," and "simulation." No time restrictions were applied. We included studies that clearly described how their PTA models were built and underwent validation from experts and/or evaluation from trainees. Articles describing a model only without any evaluation and reports in languages other than English were excluded. RESULTS: Our search initially yielded 80 articles after duplicate removal, 10 of which met our criteria and were included. Two studies trained participants on both needle aspiration and incision and drainage (I&D), four studies on I&D only, and four on needle aspiration only. 87.5% to 100% of junior residents reported minimal exposure to PTA prior to simulation. Five studies provided some form of validation to their models. The value of the simulators to train participants on skills received better appreciation than their anatomical fidelity. The perceived confidence level of trainees in managing PTA, which was assessed in 7 studies, substantially improved after training. CONCLUSION: PTA simulation improves the confidence of trainees to perform PTA drainage. There is, however, a lack of standardization and evidence regarding transfer validity among PTA simulators. The development of a standardized PTA simulator could allow for more widespread use and increase resident comfort with this procedure in a pre-clinical setting. LEVEL OF EVIDENCE: NA Laryngoscope, 2023.

The Distribution of Eight Antimicrobial Resistance Genes in Streptococcus oralis, Streptococcus sanguinis, and Streptococcus gordonii Strains Isolated from Dental Plaque as Oral Commensals.

It has been proposed that oral commensal bacteria are potential reservoirs of a wide variety of antimicrobial resistance genes (ARGs) and could be the source of pathogenic bacteria; however, there is scarce information regarding this. In this study, three common streptococci of the mitis group (S. oralis, S. sanguinis, and S. gordonii) isolated from dental plaque (DP) were screened to identify if they were frequent reservoirs of specific ARGs (blaTEM, cfxA, tetM, tetW, tetQ, ermA, ermB, and ermC). DP samples were collected from 80 adults; one part of the sample was cultured, and from the other part DNA was obtained for first screening of the three streptococci species and the ARGs of interest. Selected samples were plated and colonies were selected for molecular identification. Thirty identified species were screened for the presence of the ARGs. From those selected, all of the S. sanguinis and S. oralis carried at least three, while only 30% of S. gordonii strains carried three or more. The most prevalent were tetM in 73%, and blaTEM and tetW both in 66.6%. On the other hand, ermA and cfxA were not present. Oral streptococci from the mitis group could be considered frequent reservoirs of specifically tetM, blaTEM, and tetW. In contrast, these three species appear not to be reservoirs of ermA and cfxA.

Examining the relationship between COVID-19 and Bell's palsy: Experience of a single tertiary care center.

BACKGROUND: While the etiology of Bell's palsy (BP) is largely unknown, current evidence shows it may occur secondary to the immune response following a viral infection. Recently, BP has been reported as a clinical manifestation of coronavirus disease (COVID-19). OBJECTIVES: To investigate an association between COVID-19 infection and BP. Additionally, to evaluate the need for COVID-19 testing in patients who present with BP. METHODS: Hospital records of patients who presented to a single tertiary care center with BP in 2020 and 2021 were reviewed for presenting symptoms, demographics, COVID-19 infection and vaccination status. RESULTS: There was no statistically significant difference between patients with BP who had a positive or negative COVID test in terms of sex, BMI, age, race, smoking history or alcohol use. All 7 patients with BP and a positive COVID test were unvaccinated. Of the total cohort of 94 patients, 82 % were unvaccinated at the time of the study. None of the 17 patients who were vaccinated had a positive COVID test. A history of BP showed no statistical significance (10.3 % vs 14.3 %, p-value 0.73). CONCLUSION: We discovered a limited cohort of patients who underwent COVID-19 testing at the time of presentation for BP. Though there have been recent studies suggesting a COVID-19 and BP, we were unable to clearly identify a relationship between COVID-19 and BP. Interestingly, all patients with facial paralysis and COVID-19 were unvaccinated. To further study this relationship, we recommend consideration of a COVID-19 test for any patient that presents with facial paralysis.

Prognostic significance of time trends in treatment of head and neck squamous cell carcinoma.

PURPOSE: To analyze the impact of demographic, clinical, and management variables on time to treatment initiation (TTI) and overall survival (OS). STUDY DESIGN: Retrospective chart review. MATERIALS AND METHODS: Medical records of patients diagnosed with head and neck cancer from 2018 to 2020 were reviewed. Univariate linear and Cox-regressions identified predictors of TTI and OS. Kaplan Meier (KM) curves assessed the difference in survival by diagnostic year and TTI. RESULTS: 381 patients met eligibility criteria. Median TTI was 35.0 days (IQR: 25.0-49.0). Only 10.8 % of all patients reported any treatment delay, with TTI exceeding 90 days found in 3.7 % of patients. TTI increased with African American race (p = 0.02), ED referrals (p = 0.02), and direct admission status (p = 0.01). When compared to treatment with surgery alone, TTI was shorter in patients undergoing surgery with adjuvant radiation (p = 0.02), adjuvant chemoradiation (p = 0.04), and salvage surgery (p = 0.04). Univariate Cox-regressions found smoking (p = 0.01), direct admission status (p = 0.02), increased duration of symptoms (p = 0.02), placement of PEG tubes (p < 0.01) and tracheostomies (p < 0.01), combination treatment (p < 0.01), and surgery with adjuvant chemoradiation treatment (p = 0.01) to increase mortality risk. Disease characteristics, including tumor size (p < 0.01), presence of nodal disease (p = 0.02), and late-stage disease (p < 0.01), increased mortality risk. TTI and diagnostic year did not impact survival. CONCLUSIONS: Our analysis determined several demographic, referral, and treatment factors impacted TTI. However, increased TTI did not impact survival. Characteristics consistent with advanced disease worsened OS. Despite the pandemic burden, patients diagnosed in 2020 showed no difference in short-term survival compared to prior years.

Global Economic Burden Associated with Chronic Kidney Disease: A Pragmatic Review of Medical Costs for the Inside CKD Research Programme.

INTRODUCTION: Chronic kidney disease (CKD) is a progressive disease of growing prevalence, posing serious concerns for global public health. While the economic burden of CKD is substantial, data on the cost of CKD is limited, despite growing pressures on healthcare systems. In this review, we summarise the available evidence in 31 countries and regions and compile a library of costing methodology and estimates of CKD management and disease-associated complications across 31 countries/regions within the Inside CKD programme. METHODS: We collected country/region-specific CKD costs via a pragmatic rapid literature review of local literature and engagement with local experts. We extracted cost data and definitions from identified sources for CKD stages G3a-5, kidney failure with replacement therapy by modality, covering haemodialysis, peritoneal dialysis, and kidney transplants, and disease-associated complications in local currency, converted to United States dollars (USD) and inflated to 2022. RESULTS: Annual direct costs associated with CKD management rose by an average factor of 4 in each country/region upon progression from stage G3a to G5. Mean annual costs per patient increased considerably more from early stages versus dialysis (stage G3a, mean: $3060 versus haemodialysis, mean: $57,334; peritoneal dialysis, mean: $49,490); with estimates for annual costs of transplant also substantially higher (incident: $75,326; subsequent: $16,672). The mean annual per patient costs of complications were $18,294 for myocardial infarction, $8463 for heart failure, $10,168 for stroke and $5975 for acute kidney injury. Costing definitions varied widely in granularity and/or definition across all countries/regions. CONCLUSION: Globally, CKD carries a significant economic burden, which increases substantially with increasing disease severity. We identified significant gaps in published costs and inconsistent costing definitions. Cost-effective interventions that target primary prevention and disease progression are essential to reduce CKD burden. Our results can be used to guide cost collection and facilitate better comparisons across countries/regions to inform healthcare policy.

Pharmacokinetics of Venetoclax Co-Administered with Posaconazole in Patients with Acute Myeloid Leukemia.

The Food and Drug Administration currently approves the combination of hypomethylating agents (HMA), azacytidine or decitabine with venetoclax (VEN) for acute myeloid leukemia (AML) patients aged more than 75 years and for patients unsuitable for intensive chemotherapy. The risk of fungal infection in the early phase of treatment is not negligible; therefore, posaconazole (PCZ) is commonly administered as primary prophylaxis. A drug-drug interaction between VEN and PCZ is well known, but the trend of serum levels of venetoclax when both drugs are overlapped is not clear. In total, 165 plasma samples from 11 elderly AML patients receiving combined treatment with HMA, VEN and PCZ were analyzed by a validated analytical method (high-pressure liquid chromatography-tandem mass spectrometry). Venetoclax trough plasma concentrations were detected during the 3 days of ramp-up as well as on day 7 and day 12 of treatment when the exposure as the area under the plasma concentration-time curve and the accumulation ratio were also calculated. The results were compared with the expected data for 400 mg/dose VEN administered alone-the confirmed high inter-individual variability in pharmacokinetics suggests the need for therapeutic drug monitoring.

Olfactory dysfunction incidence and resolution amongst 608 patients with COVID-19 infection.

PURPOSE: Olfactory dysfunction (OD) is a common presenting sign of coronavirus-19 (COVID-19) infection and remains persistent in up to 7 % of patients one year after diagnosis. However, demographic, socioeconomic, and medical risk factors for persistent OD are not well understood. This study aims to determine risk factors for development and persistence of OD amongst patients with COVID-19 infection. MATERIALS AND METHODS: This prospective, observational questionnaire study was performed at a tertiary-level, academic center. Patients with history of a positive COVID-19 diagnosis were sent an online questionnaire. Patients' self-reported survey responses for OD and resolution were assessed for associations with demographic variables, socioeconomic factors, and clinical data. RESULTS: In total, 608 of 26,094 patients (77.6 % women, mean age 42.7 ± 17.4 years, range 9 months-92 years) completed the survey. OD was reported by 220 (36.2 %) patients, and 139 (63.2 %) patients achieved resolution. Patients with OD were more likely to have other sinonasal and flu-like symptoms, and had a hospitalization rate of 2.7 %. There were no significant differences in age, gender, occupational or residential factors, or medical comorbidities incidence of OD development. Women reported higher rates of persistent OD (88.9 % vs 77.0 %, p = 0.045). The OD recovery rates amongst active and resolved COVID-19 infections was 27.0 % and 70.0 %, respectively (p < 0.001). CONCLUSIONS: There was a low hospitalization rate amongst patients reporting OD. One-third of patients with COVID-19 self-reported OD, and two-thirds of patients achieve OD resolution. Survey respondents with active COVID-19 infection and female gender were more likely to report persistent OD.