A Clinical Analysis of Anti-Programmed Death-Ligand 1 (PD-L1) Immune Checkpoint Inhibitor Treatments Combined with Chemotherapy in Untreated Extensive-Stage Small-Cell Lung Cancer.

Real-world clinical experience of using anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (SCLC) patients has rarely been reported. In this study, we aimed to perform a retrospective multicenter clinical analysis of extensive-stage SCLC patients receiving first-line therapy with anti-PD-L1 ICIs combined with chemotherapy. Between November 2018 and March 2022, 72 extensive-stage SCLC patients receiving first-line atezolizumab or durvalumab in combination with chemotherapy, according to the cancer center databases of Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals, were retrospectively included in the analysis. Twenty-one patients (29.2%) received atezolizumab and fifty-one (70.8%) received durvalumab. Objective response (OR) and disease control (DC) rates of 59.7% and 73.6%, respectively, were observed with first-line ICI plus chemotherapy. The median progression-free survival (PFS) was 6.63 months (95% confidence interval (CI), 5.25-8.02), and the median overall survival (OS) was 16.07 months (95% CI, 15.12-17.0) in all study patients. A high neutrophil-to-lymphocyte ratio (NLR; >4) and a high serum lactate dehydrogenase (LDH) concentration (>260 UL) were identified as independent unfavorable factors associated with shorter OS in the multivariate analysis. Regarding safety, neutropenia was the most common grade 3 treatment-related adverse event (AE), but no treatment-related deaths occurred in the study patients. First-line anti-PD-L1 ICIs combined with chemotherapy are effective and safe for male extensive-stage SCLC patients. Further therapeutic strategies may need to be developed for patients with unfavorable outcomes (e.g., baseline high NLR and serum LDH level).

Differential prognostic value of tumor and plasma T790M mutations in EGFR TKI-treated advanced NSCLC.

Background: Substitution of methionine for threonine at codon 790 (T790M) of epidermal growth factor receptor (EGFR) represents the major mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small-cell lung cancer. We determined the prognostic impact and association of secondary T790M mutations with the outcomes of osimertinib and chemotherapy. Methods: Patients (n = 460) progressing from first-line EGFR-TKI treatment were assessed. Tissue and/or liquid biopsies were used to determine T790M status; post-progression overall survival (OS) was analyzed. Results: Overall, 143 (31.1%) patients were T790M positive, 95 (20.7%) were T790M negative, and 222 (48.2%) had unknown T790M status. T790M status [T790M positive versus T790M negative: hazard ratio (HR) 0.48 (95% confidence interval (CI), 0.32-0.70); p < 0.001, T790M unknown versus T790M negative: HR 1.97 (95% CI, 1.47-2.64); p < 0.001] was significantly associated with post-progression OS. T790M positivity rates were similar for tissue (90/168, 53.6%) and liquid (53/90, 58.9%) biopsies (Fisher's exact test, p = 0.433). Tumor T790M-positive patients had significantly longer post-progression OS than tumor T790M-negative patients (34.1 versus 17.1 months; log-rank test, p = 8 × 10-5). Post-progression OS was similar between plasma T790M-positive and -negative patients (17.4 versus not reached; log-rank test, p = 0.600). In tumor T790M-positive patients, post-progression OS was similar after osimertinib and chemotherapy [34.1 versus 29.1 months; log-rank test, p = 0.900; HR 1.06 (95% CI, 0.44-2.57); p = 0.897]. Conclusion: T790M positivity predicts better post-progression OS than T790M negativity; tumor T790M positivity has a stronger prognostic impact than plasma T790M positivity. Osimertinib and chemotherapy provide similar OS benefits in patients with T790M-positive tumors.

Different prognostic meaning of tumor resistant gene detected from tumor or blood in patients with EGFR-mutant lung cancer The study demonstrates that patients with EGFR-mutant lung cancer who develop resistance due to a secondary T790M mutation, defined by tumor or blood T790M positivity, achieve better survival than patients without secondary T790M mutation; this association was mainly contributed by tumour T790M positivity. Oismertinib and chemotherapy led to similar survival in tumour T790M-positive patients. However, compared to osimertinib, chemotherapy was associated with longer survival in blood T790M-positive patients.

What do primary care providers want to know when caring for patients living with frailty? An analysis of eConsult communications between primary care providers and specialists.

BACKGROUND: Frailty is a complex condition that primary care providers (PCPs) are managing in increasing numbers, yet there is no clear guidance or training for frailty care. OBJECTIVES: The present study examined eConsult questions PCPs asked specialists about patients with frailty, the specialists' responses, and the impact of eConsult on the care of these patients. DESIGN: Cross-sectional observational study. SETTING: ChamplainBASE™ eConsult located in Eastern Ontario, Canada. PARTICIPANTS: Sixty one eConsult cases closed by PCPs in 2019 that use the terms "frail" or "frailty" to describe patients 65 years of age or older. MEASUREMENTS: The Taxonomy of Generic Clinical Questions (TGCQ) was used to classify PCP questions and the International Classification for Primary Care 3 (ICPC-3) was used to classify the clinical content of each eConsult. The impact of eConsult on patient care was measured by PCP responses to a mandatory survey. RESULTS: PCPs most frequently directed their questions to cardiology (n = 7; 11%), gastroenterology (n = 7; 11%), and endocrinology (n = 6; 10%). Specialist answers most often pertained to medications (n = 63, 46%), recommendations for clinical investigation (n = 24, 17%), and diagnoses (n = 22, 16%). Specialist responses resulted in PCPs avoiding referral in 57% (n = 35) of cases whereas referrals were still required in 15% (n = 9) of cases. Specialists responded to eConsults in a median 1.11 days (IQR = 0.3-4.7), and 95% (n = 58) of cases received a response within 7 days. Specialists recorded a median of 15 min to respond (IQR = 10-20), with a median cost of $50.00 CAD (IQR = 33.33 - 66.66) per eConsult. CONCLUSIONS: Through the analysis of questions and responses submitted to eConsult, this study provides novel information on PCP knowledge gaps and approaches to care for patients living with frailty. Furthermore, these analyses provide evidence that eConsult is a feasible and valuable tool for improving care for patients with frailty in primary care settings.

Factors associated with prolonged progression-free survival of patients treated with first-line afatinib for advanced epidermal growth factor receptor-mutated non-small cell lung cancer.

BACKGROUND: This study aimed to investigate the factors associated with prolonged progression-free survival (PFS) (>36 months) of advanced non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations treated with first-line afatinib. METHODS: We performed a retrospective analysis of data of patients with advanced EGFR-mutated NSCLC receiving first-line afatinib at two tertiary care referral centers, Linkou and Kaohsiung Chang Gung Memorial Hospital, in Taiwan between June 2014 and April 2022. RESULTS: The data of 546 treatment-naïve EGFR-mutated advanced NSCLC patients were analyzed. Median PFS and overall survival were 14.5 months and 27.2 months, respectively. The PFS of 462 patients (84.6%) was less than 36 months and of 84 patients (15.4%) was more than 36 months. The PFS > 36 months group had a significantly higher percentage of patients with uncommon mutations (p = 0.002). The PFS ≤36 months group had significantly higher incidences of bone, liver, and adrenal metastases (all p < 0.05) and a higher rate of multiple distant metastases. Multivariate logistic regression analysis showed that liver metastasis was negatively and independently associated with prolonged PFS (adjusted odds ratio = 0.246 [95% CI: 0.067-0.908], p = 0.035). The median overall survival of the PFS >36 months group was 46.0 months and that of the PFS ≤36 months group was 22.9 months (log-rank test, p < 0.001). CONCLUSIONS: We found that EGFR-mutated NSCLC patients receiving first-line afatinib were prone to shorter PFS if they had distant organ metastasis, especially liver metastasis.

Brain metastasis, EGFR mutation subtype and generation of EGFR-TKI jointly influence the treatment outcome of patient with EGFR-mutant NSCLC.

Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation is brain metastasis (BM)-prone. We determined the impact of this hallmark, along with EGFR subtype and generation of tyrosine kinase inhibitor (TKI) treatment, on patients' outcome. 553 metastatic EGFR-mutant NSCLC patients received front-line EGFR-TKI treatment. Progression-free survival (PFS), overall survival (OS) and secondary T790M rate were analysed. BM was observed in 211 (38.2%) patients. BM (HR 1.20 [95% CI 0.99-1.48]; p = 0.053), ECOG PS 0-1 (HR 0.71 [95% CI 0.54-0.93]; p = 0.014) and afatinib treatment (HR 0.81 [95% CI 0.66-0.99]; p = 0.045) were associated with PFS. Afatinib-treated patients without BM demonstrated a significantly longer PFS (16.3 months) compared to afatinib-treated patients with BM (13.7 months) and to gefitinib/erlotinib-treated patients with (11.1 months) or without BM (14.2 months; p < 0.001). CNS-only progression trended higher in afatinib-treated patients. ECOG PS 0-1 (HR 0.41 [95% CI 0.31-0.56]; p < 0.001) and EGFR L858R mutation (HR 1.46 [95% CI 1.13-1.88]; p = 0.003), but not BM, were the predictors for OS. BM (OR 2.02 [95% CI 1.02-4.08]; p = 0.040), afatinib treatment (OR 0.26 [95% CI 0.12-0.50]; p < 0.001) and EGFR L858R mutation (OR 0.55 [95% CI 0.28-1.05]; p = 0.070) were associated with secondary T790M rate. In BM patients, gefitinib/erlotinib-treated ones with 19 deletion mutation and afatinib-treated ones with L858R mutation had the highest and the lowest T790M rate (94.4% vs. 27.3%, p < 0.001), respectively. BM and generation of EGFR-TKI jointly impact PFS and secondary T790M rate in patients with EGFR-mutant NSCLC, whereas OS was mainly associated with EGFR subtype.

Sequential treatment in advanced epidermal growth factor receptor-mutated lung adenocarcinoma patients receiving first-line bevacizumab combined with 1st/2nd-generation EGFR-tyrosine kinase inhibitors.

Introduction: The clinical outcomes of sequential treatment of advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with first-line bevacizumab combined with 1st/2nd-generation EGFR-TKIs are unclear. Thus, we aimed to analyze the outcomes of these patients. Methods: Between January 2015 and December 2020, data for 102 advanced EGFR-mutated lung adenocarcinoma patients receiving first-line bevacizumab combined with erlotinib or afatinib followed by treatments at multiple institutions were retrospectively analyzed. All patients with progressive disease (PD) after first-line therapy underwent secondary T790M mutation detection. Results: The secondary T790M mutation positive rate of all study patients was 57.9%. First-line erlotinib use and progression-free survival (PFS) after first-line therapy > 12 months were positively associated with the T790M mutation (P <0.05). The response rates (RRs) to second-line treatments were 51.7% and 22.7% for the osimertinib and nonosimertinib groups, respectively (P = 0.001). The median PFS associated with second-line osimertinib and nonosimertinib therapy was 13.7 and 7.1 months, respectively (hazard ratio (HR) = 0.38; 95% confidence interval (CI), 0.23-0.63; P< 0.001). Patients with a secondary T790M mutation receiving second-line osimertinib treatment had a median overall survival (OS) of 54.3 months, and the median OS was 31.9 months for non-T790M-mutated patients receiving second-line nonosimertinib treatments (HR = 0.36; CI: 0.21-0.62, P < 0.001). Conclusion: The majority of acquired resistance to first-line bevacizumab combined with 1st/2nd-generation EGFR-TKIs is associated with the T790M mutation. Sequential osimertinib treatment in patients with positive secondary T790M mutation is associated with better outcomes among these patients.

Barriers and facilitators to participation in exercise prehabilitation before cancer surgery for older adults with frailty: a qualitative study.

BACKGROUND: Older adults with frailty are at an increased risk of adverse outcomes after surgery. Exercise before surgery (exercise prehabilitation) may reduce adverse events and improve recovery after surgery. However, adherence with exercise therapy is often low, especially in older populations. The purpose of this study was to qualitatively assess the barriers and facilitators to participating in exercise prehabilitation from the perspective of older people with frailty participating in the intervention arm of a randomized trial. METHODS: This was a research ethics approved, nested descriptive qualitative study within a randomized controlled trial of home-based exercise prehabilitation vs. standard care with older patients (≥ 60 years) having elective cancer surgery, and who were living with frailty (Clinical Frailty Scale ≥ 4). The intervention was a home-based prehabilitation program for at least 3 weeks before surgery that involved aerobic activity, strength and stretching, and nutritional advice. After completing the prehabilitation program, participants were asked to partake in a semi-structured interview informed by the Theoretical Domains Framework (TDF). Qualitative analysis was guided by the TDF. RESULTS: Fifteen qualitative interviews were completed. Facilitators included: 1) the program being manageable and suitable to older adults with frailty, 2) adequate resources to support engagement, 3) support from others, 4) a sense of control, intrinsic value, noticing progress and improving health outcomes and 5) the program was enjoyable and facilitated by previous experience. Barriers included: 1) pre-existing conditions, fatigue and baseline fitness, 2) weather, and 3) guilt and frustration when unable to exercise. A need for individualization and variety was offered as a suggestion by participants and was therefore described as both a barrier and facilitator. CONCLUSIONS: Home-based exercise prehabilitation is feasible and acceptable to older people with frailty preparing for cancer surgery. Participants identified that a home-based program was manageable, easy to follow with helpful resources, included valuable support from the research team, and they reported self-perceived health benefits and a sense of control over their health. Future studies and implementation should consider increased personalization based on health and fitness, psychosocial support and modifications to aerobic exercises in response to adverse weather conditions.

Changing the channel: a qualitative analysis of an innovative video intervention to explore resident attitudes towards interprofessional collaboration on a Geriatric Medicine Unit.

Background: Medical learners develop a more positive attitude toward Interprofessional Collaboration (IPC) following Interprofessional Education (IPE) programs. However, IPE is not standardized, and the most effective teaching tool is unclear. The purpose of our study was to develop an IPE teaching tool for medical residents during an inpatient geriatric medicine rotation at an academic hospital, evaluate and explore the impact of the program on resident attitudes towards teamwork, and identify barriers and facilitators to interprofessional collaboration. Methods: An innovative video was developed which simulated a common IPC scenario. Near the start of the rotation, learners watched the video then participated in a facilitated discussion around principles of IPE, using the Canadian Interprofessional Health Collaborative (CIHC) framework, which highlights interprofessional communication, patient-centered care, role clarification, team functioning, collaborative leadership, and interprofessional conflict resolution. At the end of their four-week rotation, focus groups were conducted to explore resident attitudes towards IPE. The Theoretical Domain Framework (TDF) was used for qualitative analysis. Results: Data from 23 participants in five focus groups were analyzed using the TDF framework. Residents were able to identify barriers and facilitators to IPC in five TDF domains: environmental context and resources, social/professional role and identity, knowledge, social influences, and skills. Their observations correlated with the CIHC framework. Conclusion: The use of a scripted video and facilitated group discussion gave insights into residents' attitudes, perceived barriers, and facilitators towards IPC on a geriatric medicine unit. Future research could explore the use of this video intervention in other hospital services where team-based care is important.

Contexte: Les apprenants en médecine développent une attitude plus positive à l'égard de la collaboration interprofessionnelle (CIP) après avoir suivi un programme de formation interprofessionnelle (FIP). Toutefois, la FIP n'est pas standardisée et on ne sait pas quel outil d'enseignement est le plus efficace. Le but de notre étude était d'élaborer un outil de FIP pour les résidents en stage de gériatrie dans un hôpital universitaire, d'évaluer et d'explorer les effets du programme sur les attitudes des résidents à l'égard du travail d'équipe, et de recenser les facteurs qui entravent ou facilitent la collaboration interprofessionnelle. Méthodes: Une capsule vidéo innovante simulant un scénario courant de CIP a été créée. Au début de leur stage de résidence, les apprenants ont regardé la capsule et participé à une discussion animée sur les principes de la CIP, conformément au référentiel du Consortium pancanadien pour l'interprofessionnalisme en santé (CPIS), qui prône notamment la communication interprofessionnelle, les soins centrés sur le patient, la clarification des rôles, le fonctionnement de l'équipe, le leadership collaboratif et la résolution des conflits interprofessionnels. À la fin de leur stage de quatre semaines, des groupes de discussion ont été organisés pour explorer les attitudes des résidents à l'égard de la CIP. Un cadre de domaines théoriques (Theoretical Domains Framework) a été appliqué pour réaliser l'analyse qualitative. Conclusion: Au moyen d'une capsule scénarisée et d'une discussion de groupe dirigée, nous avons pu cerner les attitudes des résidents d'une unité de gériatrie par rapport à la CIP ainsi que leurs perceptions quant aux facteurs qui peuvent l'entraver ou la faciliter. Des travaux futurs pourraient explorer le recours à cette formule d'enseignement de la CIP dans d'autres services hospitaliers où les soins en équipe sont importants.

Influence of preoperative frailty on quality of life after cardiac surgery: A systematic review and meta-analysis.

BACKGROUND: Frailty has emerged as an important prognostic marker of increased mortality after cardiac surgery, but its association with quality of life (QoL) and patient-centered outcomes is not fully understood. We sought to evaluate the association between frailty and such outcomes in older patients undergoing cardiac surgery. METHODS: This systematic review included studies evaluating the effect of preoperative frailty on QoL outcomes after cardiac surgery amongst patients 65 years and older. The primary outcome was patient's perceived change in QoL following cardiac surgery. Secondary outcomes included residing in a long-term care facility for 1 year, readmission in the year following the intervention, and discharge destination. Screening, inclusion, data extraction, and quality assessment were performed independently by two reviewers. Meta-analyses based on the random-effects model were conducted. The evidential quality of findings was assessed with the GRADE profiler. RESULTS: After the identification of 3105 studies, 10 observational studies were included (1580 patients) in the analysis. Two studies reported on the change in QoL following cardiac surgery, which was higher for patients with frailty than for patients without. Preoperative frailty was associated with both hospital readmission (pooled odds ratio [OR] 1.48 [0.80-2.74], low GRADE level) as well as non-home discharge (pooled OR 3.02 [1.57-5.82], moderate GRADE level). CONCLUSION: While evidence in this field is limited by heterogeneity of frailty assessment and non-randomized data, we demonstrated that baseline frailty may possibly be associated with improved QoL, but with increased readmission as well as discharge to a non-home destination following cardiac surgery. These patient-centered outcomes are important factors when considering interventional options for older patients. STUDY REGISTRATION: OSF registries (https://osf.io/vm2p8).

Changes in tongue morphology predict responses in pharyngeal patency to selective hypoglossal nerve stimulation.

STUDY OBJECTIVES: The major goal of the study was to determine whether changes in tongue morphology under selective hypoglossal nerve therapy for obstructive sleep apnea were associated with alterations in airway patency during sleep when specific portions of the hypoglossal nerve were stimulated. METHODS: This case series was conducted at the Johns Hopkins Sleep Disorders Center at Johns Hopkins Bayview Medical Center. Twelve patients with apnea implanted with a multichannel targeted hypoglossal nerve-stimulating system underwent midsagittal ultrasound tongue imaging during wakefulness. Changes in tongue shape were characterized by measuring the vertical height and polar dimensions between tongue surface and genioglossi origin in the mandible. Changes in patency were characterized by comparing airflow responses between stimulated and adjacent unstimulated breaths during non-rapid eye movement sleep. RESULTS: Two distinct morphologic responses were observed. Anterior tongue base and hyoid-bone movement (5.4 [0.4] to 4.1 [1.0] cm (median and [interquartile range]) with concomitant increases in tongue height (5.0 [0.9] to 5.6 [0.7] cm) were associated with decreases in airflow during stimulation. In contrast, comparable anterior hyoid movement (tongue protrusion from 5.8 [0.5] to 4.5 [0.9] cm) without significant increases in height (5.2 [1.6] to 4.6 [0.8] cm) were associated with marked increases in airflow during sleep. CONCLUSIONS: Tongue protrusion with preservation of tongue shape predicted increases in patency, whereas anterior movement with concomitant increases in height were associated with decreased pharyngeal patency. These findings suggest that pharyngeal patency can be best stabilized by stimulating lingual muscles that maintain tongue shape while protruding the tongue, thereby preventing it from prolapsing posteriorly during sleep. CITATION: Fleury Curado T, Pham L, Otvos T, et al. Changes in tongue morphology predict responses in pharyngeal patency to selective hypoglossal nerve stimulation. J Clin Sleep Med. 2023;19(5):947-955.

Afatinib in Untreated Stage IIIB/IV Lung Adenocarcinoma with Major Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations (G719X/L861Q/S768I): A Multicenter Observational Study in Taiwan.

BACKGROUND: Real-world clinical experience with afatinib as a treatment for advanced lung adenocarcinoma harboring uncommon epidermal growth factor receptor (EGFR) mutations (G719X, L861Q and S768I) has rarely been reported. OBJECTIVE: We aimed to perform a retrospective multicenter study to analyze afatinib therapy in untreated advanced lung adenocarcinoma harboring uncommon EGFR mutations. PATIENTS AND METHODS: Between May 2014 and June 2021, the data of 90 stage IIIB/IV lung adenocarcinoma patients with uncommon EGFR mutations (G719X/L861Q/S768I) treated with first-line afatinib from the cancer center database of Linkou, Tucheng, and Kaohsiung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed. RESULTS: Afatinib had an objective response rate (ORR) of 63.3% and a disease control rate (DCR) of 86.7%. The median progression-free survival (PFS) with first-line afatinib therapy was 17.3 months (95% confidence interval (CI), 12.07-22.53), and the median overall survival (OS) was 28.5 months (95% CI, 20.22-36.77) in all study patients. In the multivariate analysis, poor performance (Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2) and brain and liver metastases were independent predictors of unfavorable PFS. The G719X mutation (alone+compound) was an independent predictor of favorable PFS (hazard ratio (HR) = 0.578; 95% CI, 0.355-0.941; P = 0.027). Most afatinib-related adverse events (AEs) were limited to grades 1 and 2 and were manageable. CONCLUSIONS: First-line afatinib therapy is effective and safe for advanced lung adenocarcinoma harboring uncommon EGFR mutations. The G719X mutation was an independent factor associated with a favorable outcome. Poor performance (ECOG PS ≥ 2), brain metastasis, and liver metastasis were predictive factors of shorter PFS with first-line afatinib therapy.

Value of Surgical and Nonsurgical Treatment for Sleep Apnea: A Closer Look at Health Care Utilization.

OBJECTIVE: To determine how surgery, continuous positive airway pressure (CPAP), and no treatment impact health care utilization in patients who have obstructive sleep apnea (OSA). STUDY DESIGN: This is a retrospective cohort study of patients between the ages of 18 and 65 that were diagnosed with OSA (9th International Classification of Diseases) from January 2007 to December 2015. Data were collected over 2 years, and prediction models were generated to evaluate trends over time. SETTING: A population-based study using real-world data and insurance databases. METHODS: A total of 4,978,649 participants were identified, all with at least 25 months of continuous enrollment. Patients with previous soft tissue procedures not approved for OSA (nasal surgery), or without continuous insurance coverage were excluded. A total of 18,050 patients underwent surgery, 1,054,578 were untreated, and 799,370 received CPAP. IBM Marketscan Research database was utilized to describe patient-specific clinical utilization, and expenditures, across outpatient, and inpatient services, and medication prescriptions. RESULTS: When the cost of the intervention was eliminated in the 2-year follow-up, the monthly payments of group 1 (surgery) were significantly less than group 3 (CPAP) in overall, inpatient, outpatient, and pharmaceutical payments (p < .001). The surgery group was associated with less cumulative payments compared to the other 2 groups when the cost of the intervention (CPAP or surgery) was eliminated in all comorbidities and age groups. CONCLUSION: Treating OSA with surgery can lessen overall health care utilization compared to no treatment and CPAP.

Effects of dexamethasone use on viral clearance among patients with COVID-19: a multicenter cohort study.

OBJECTIVES: This study explored the outcomes and predictors of early viral clearance among patients with COVID-19. METHODS: This study recruited consecutive patients from March 1, 2020 to July 31, 2021. Early viral clearance was defined as having a duration from symptom onset to successive detection of SARS-CoV-2 polymerase chain reaction cycle threshold (Ct) value of ≥30 within 10 days. RESULTS: Among the 239 enrolled patients, 54.4% (130 patients) had early viral clearance. A multivariate logistic regression analysis identified that dexamethasone use and day 1 Ct values were independent factors associated with late viral clearance. Patients with mild-moderate severity and who received dexamethasone therapy had a longer time to viral clearance than those who did not receive dexamethasone (17.2 ± 1.8 days vs 12.3 ± 1.1 days, P = 0.018). Patients with severe-critical severity had a similar duration from symptom onset to Ct value ≥30, regardless of dexamethasone therapy (18.3 ± 0.9 days vs 16.7 ± 4.7 days, P = 0.626). CONCLUSION: The study revealed that dexamethasone therapy and Ct values are independent predictors of late viral clearance. Patients with severe disease course due to older age, increased number of comorbidities, and worse clinical outcomes experienced delayed viral clearance.

A systematic review of perioperative clinical practice guidelines for care of older adults living with frailty.

BACKGROUND: Perioperative frailty is prevalent and requires complex management, which could be guided by clinical practice guidelines (CPGs). The objective of this systematic review was to identify and synthesise CPGs that provide perioperative recommendations specific to older adults living with frailty. METHODS: After protocol registration, we performed a systematic review of CPGs. MEDLINE, Embase, CINAHL, and 14 grey literature databases were searched (January 1, 2000 until December 22, 2021). We included all CPGs that contained at least one frailty-specific recommendation related to any phase of the perioperative period. We compiled all relevant recommendations, extracted underlying strength of evidence, and categorised them by perioperative phase of care. Within each phase, recommendations were synthesised inductively into themes. Quality of CPGs was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. RESULTS: From 4707 citations, 13 guidelines were included; 8/13 were focused on the perioperative care of older surgical patients in general. Among 110 recommendations extracted, 37 themes were generated, with the majority pertaining to preoperative care. Four themes were supported by strong evidence: performing preoperative frailty assessments, using multidimensional frailty instruments, reducing urinary catheter use, and following multidisciplinary care and communication throughout the perioperative period. Per AGREE II, most guidelines (8/13; 62%) were recommended for use with modifications. CONCLUSIONS: Despite increasing numbers of patients living with frailty, few guidelines exist that address frailty-specific perioperative care. Given the lack of strong evidence-based recommendations, particularly outside the preoperative period, high-quality primary research is required to underpin future guidelines and better inform the care of older surgical patients with frailty. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42022320149.

Clinical and laboratory predictors for disease progression in patients with COVID-19: A multi-center cohort study.

BACKGROUND: Reliable clinical and laboratory predictors of coronavirus disease 2019 (COVID-19) disease progression could help to identify the subset of patients who are susceptible to severe symptoms. This study sought to identify the predictors for disease progression in patients with COVID-19. METHODS: This study recruited consecutive patients from four hospitals between March 1, 2020, and July 31, 2021. Demographic characteristics, laboratory results, and clinical outcomes were collected. RESULTS: Among the 239 enrolled patients, 39.3% (94/239) experienced in-hospital disease progression. Multivariate logistic regression revealed that coronary arterial disease (CAD) (OR, 4.15; 95% C.I., 1.47-11.66), cerebrovascular attack (CVA) (OR, 12.98; 95% C.I., 1.30-129.51), platelet count < median value (OR, 3.23; 95% C.I., 1.65-6.32), and C-reactive protein (CRP) levels > median value of (OR, 2.25; 95% C.I., 1.02-4.99) were independent factors associated with COVID-19 progression. Patients who underwent disease progression at days 1, 4, and 7 presented lower lymphocyte counts and higher CRP levels, compared to patients without disease progression. CONCLUSIONS: The study revealed that in hospitalized COVID-19 patients, comorbidity with CAD and CVA, low platelet count, and elevated CRP levels were independently associated with disease progression. Compared with patients without disease progression, those with disease progression presented persistently low lymphocyte counts and elevated CRP levels.

Patient's Perception of Nasal Function and Cosmesis After Maxillomandibular Advancement for Obstructive Sleep Apnea.

Background: Maxillomandibular advancement (MMA) remains one of the most effective surgeries for the treatment of obstructive sleep apnea (OSA), but it can be difficult to manage nasal and midfacial esthetics for patients requiring significant maxillary advancement. Objective: To evaluate changes in the Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) after the modified MMA approach. Methods: This prospective study was conducted on subjects undergoing MMA at a tertiary referral center from September 2020 to August 2021. Nasal function, cosmesis, and sleepiness were assessed perioperatively with the SCHNOS, visual analog scale for nasal function and cosmesis, and Epworth sleepiness scale (ESS). Objective polysomnography data were also investigated. Results: Thirty-one subjects met inclusion criteria. After MMA, SCHNOS-O (obstruction domain) improved from 44.38 ± 26.21 to 19.03 ± -4.75 (p < 0.001). The SCHNOS-C (cosmesis domain) improved significantly from 13.95 ± 19.32 to 5.27 ± 8.93 (p = 0.029). Specific items evaluating self-esteem, nasal straightness, and symmetry showed significant improvement (p = 0.006, 0.025, 0.044). The ESS also improved from 9.41 ± 6.11 to 3.26 ± 3.03 (p < 0.001), and it correlated with nasal obstruction scores. Conclusion: In this study, patients' perception of nasal obstruction and appearance improved after applying the nasal modifications to MMA described for OSA.

Blood transcriptomic biomarkers of alcohol consumption and cardiovascular disease risk factors: the Framingham Heart Study.

BACKGROUND: The relations of alcohol consumption and gene expression remain to be elucidated. MATERIALS AND METHODS: We examined cross-sectional associations between alcohol consumption and whole blood derived gene expression levels and between alcohol-associated genes and obesity, hypertension, and diabetes in 5531 Framingham Heart Study (FHS) participants. RESULTS: We identified 25 alcohol-associated genes. We further showed cross-sectional associations of 16 alcohol-associated genes with obesity, nine genes with hypertension, and eight genes with diabetes at P < 0.002. For example, we observed decreased expression of PROK2 (ß = -0.0018; 95%CI: -0.0021, -0.0007; P = 6.5e - 5) and PAX5 (ß = -0.0014; 95%CI: -0.0021, -0.0007; P = 6.5e - 5) per 1 g/day increase in alcohol consumption. Consistent with our previous observation on the inverse association of alcohol consumption with obesity and positive association of alcohol consumption with hypertension, we found that PROK2 was positively associated with obesity (OR = 1.42; 95%CI: 1.17, 1.72; P = 4.5e - 4) and PAX5 was negatively associated with hypertension (OR = 0.73; 95%CI: 0.59, 0.89; P = 1.6e - 3). We also observed that alcohol consumption was positively associated with expression of ABCA13 (ß = 0.0012; 95%CI: 0.0007, 0.0017; P = 1.3e - 6) and ABCA13 was positively associated with diabetes (OR = 2.57; 95%CI: 1.73, 3.84; P = 3.5e - 06); this finding, however, was inconsistent with our observation of an inverse association between alcohol consumption and diabetes. CONCLUSIONS: We showed strong cross-sectional associations between alcohol consumption and expression levels of 25 genes in FHS participants. Nonetheless, complex relationships exist between alcohol-associated genes and CVD risk factors.

Plasma thrombomodulin levels are associated with acute kidney injury in patients with acute heart failure.

Cardiorenal syndrome type I (CRS I) is defined as the development of acute kidney injury (AKI) following acute decompensated heart failure (ADHF). The clinical significance of endothelial markers in ADHF-associated AKI has yet to be clarified. This study therefore investigated the biological processes linking ADHF and AKI with the aim of determining whether the plasma markers of endothelial injury and activation are associated with AKI in patients with ADHF. The study prospectively recruited 125 consecutive patients admitted to a coronary critical unit due to ADHF. Patients with and without AKI were compared in terms of soluble thrombomodulin (sTM), angiopoietin (Ang)-1 and -2 plasma levels as well as baseline characteristics. Among the study population, 14 (11.2%) patients developed CRS within 7 days after admission. The hemoglobin levels (median [IQR]11.3[10.8-12.6] vs. 13.5 [12.2-15.0] g/dL, p = 0.003) and baseline eGFR (66.5[35.7-87.9] vs. 78.5 [64.9-107.5] mL/minute/1.73m2, p = 0.044) of patients with CRS were lower than those of patients without CRS. Patients with CRS also presented elevated plasma levels of BNP (1317.5 [222.6-3375.5] vs. 258.2 [63.2-925.8] pg/mL, p = 0.008), Ang-2 (3993.0 [1561.3-15722.7] vs. 1805.9 [1196.9-3302.3] pg/mL, p = 0.006), and sTM (6665.7 [4707.1-11947.3] vs. 4132.2 [3338.0-5531.8] ng/mL, p < 0.001), compared to patients without CRS. Multivariate logistic regression analysis based on forward stepwise method identified that log sTM was the only independent risk factor for AKI (OR, 13.83; 3.02-63.28, p = 0.001). Furthermore, higher sTM levels were associated with AKI in patients with ADHF. These findings suggest a novel approach to dealing with kidney injury in the context of ADHF, involving the use of baseline biomarker profiles to identify individuals at risk of developing AKI.KEY MESSAGESThe clinical significance of endothelial markers in acute decompensated heart failure (ADHF)-associated acute kidney injury (AKI) has not previously been clarified. This study revealed that markers of endothelial injury (i.e. plasma soluble thrombomodulin (sTM) levels) were higher in ADHF patients with AKI than in those without AKI.Multivariate analysis identified sTM level > cutoff value of 4,855.2 pg/mL as an independent factor associated with the development of AKI. sTM could potentially be used as a biomarker to predict the development of AKI in patients with heart failure.These findings suggest a novel approach to dealing with kidney injury in the context of ADHF, involving the use of baseline biomarker profiles to identify individuals at risk of developing AKI.

Comparison of Clinical Characteristics and Outcomes of Hospitalized Patients Infected with the D614G Strain or Alpha Variant of COVID-19 in Taiwan: A Multi-Center Cohort Study.

Objective: Direct comparison of the clinical traits of coronavirus disease 2019 (COVID-19) in strain D614G, which originated from Wuhan, China, and the Alpha variant, which contains 17 mutations, infected patients could help physicians distinguish between strains and make clinical decisions accordingly. This study sought to compare the clinical characteristics and outcomes of the D614G strain and Alpha variant of SARS-COV-2 and identify the predictors for viral RNA clearance and in-hospital mortality in patients with COVID-19. Methods: This study recruited consecutive patients from four hospitals between March 1, 2020, and July 31, 2021. Demographic characteristics, laboratory results, and clinical outcomes were determined. Results: Among the 239 enrolled patients, 11.2% (27/239) were infected with strain D614G and 88.7% (212/239) were infected with the Alpha variant. There were no significant differences in disease progression, rate of respiratory failure, subsequent development of acute respiratory distress syndrome (ARDS), acute kidney injury, cardiac injury, duration of stay in the intensive care unit or hospital, discharge rate, mortality rate, or viral RNA clearance time between the two groups. Multivariate Cox regression revealed that antibiotic therapy reduced the risk of delayed viral RNA clearance (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.13-0.55), while autoimmune disease increased the risk of delayed viral RNA clearance (HR, 3.98; 95% CI, 1.21-13.04). Elderly patients (age > 65 years) and patients with a history of cerebrovascular accident (CVA) were at increased risk of in-hospital mortality (HR, 5.14; 95% CI, 1.06-24.72 and HR, 3.62; 95% CI, 1.25-10.42, respectively). Conclusions: There were no significant differences between the D614G strain and Alpha variant of COVID-19 in terms of clinical characteristics and outcomes. However, factors affecting viral RNA clearance and the risk of in-hospital mortality were identified. These results could help to inform the future prioritization of resource allocation and identify patients in need of intense monitoring.

Identifying barriers and facilitators to routine preoperative frailty assessment: a qualitative interview study.

PURPOSE: Preoperative frailty assessment is recommended by multiple practice guidelines and may improve outcomes, but it is not routinely performed. The barriers and facilitators of routine preoperative frailty assessment have not been formally assessed. Our objective was to perform a theory-guided evaluation of barriers and facilitators to preoperative frailty assessment. METHODS: This was a research ethics board-approved qualitative study involving physicians who perform preoperative assessment (consultant and resident anesthesiologists and consultant surgeons). Semistructured interviews were conducted by a trained research assistant informed by the Theoretical Domains Framework to identify barriers and facilitators to frailty assessment. Interview transcripts were independently coded by two research assistants to identify specific beliefs relevant to each theoretical domain. RESULTS: We interviewed 28 clinicians (nine consultant anesthesiologists, nine consultant surgeons, and ten anesthesiology residents). Six domains (Knowledge [100%], Social Influences [96%], Social Professional Role and Identity [96%], Beliefs about Capabilities [93%], Goals [93%], and Intentions [93%]) were identified by > 90% of respondents. The most common barriers identified were prioritization of other aspects of assessment (e.g., cardio/respiratory) and a lack of awareness of evidence and guidelines supporting frailty assessment. The most common facilitators were a high degree of familiarity with frailty, recognition of the importance of frailty assessment, and strong intentions to perform frailty assessment. CONCLUSION: Barriers and facilitators to preoperative frailty assessment are multidimensional, but generally consistent across different types of perioperative physicians. Knowledge of barriers and facilitators can guide development of evidence-based strategies to increase frailty assessment.

RéSUMé: OBJECTIF: L'évaluation préopératoire de la fragilité est recommandée par plusieurs lignes directrices de pratique et pourrait améliorer les devenirs, mais elle n'est pas systématiquement réalisée. Les obstacles et les facilitateurs de l'évaluation de routine de la fragilité préopératoire n'ont pas été officiellement évalués. Notre objectif était de mener une évaluation théorique des obstacles et des facilitateurs de l'évaluation préopératoire de la fragilité. MéTHODE: Il s'agissait d'une étude qualitative approuvée par le comité d'éthique de la recherche impliquant des médecins menant des évaluations préopératoires (anesthésiologistes, résidents en anesthésiologie et chirurgiens). Des entrevues semi-structurées ont été réalisées par un assistant de recherche formé en se fondant sur le Cadre des domaines théoriques afin d'identifier les obstacles et les facilitateurs à l'évaluation de la fragilité. Les transcriptions des entrevues ont été codées de manière indépendante par deux assistants de recherche afin d'identifier les croyances spécifiques pertinentes à chaque domaine théorique. RéSULTATS: Nous avons interrogé 28 cliniciens (neuf anesthésiologistes, neuf chirurgiens et dix résidents en anesthésiologie). Six domaines (Connaissances [100 %], Influences sociales [96 %], Rôle et identité socio-professionnels [96 %], Croyances concernant les capacités [93 %], Objectifs [93 %] et Intentions [93 %]) ont été identifiés par > 90 % des répondants. Les obstacles les plus fréquemment cités étaient la priorisation accordée à d'autres aspects de l'évaluation (p. ex., cardio/respiratoire) et le manque de connaissances des données probantes et des lignes directrices à l'appui de l'évaluation de la fragilité. Les facilitateurs les plus courants étaient un degré élevé de familiarité avec la fragilité, la reconnaissance de l'importance de l'évaluation de la fragilité et de fortes intentions de réaliser une évaluation de la fragilité. CONCLUSION: Les obstacles et les facilitateurs de l'évaluation préopératoire de la fragilité sont multidimensionnels, mais généralement uniformes parmi les différents types de médecins périopératoires. La connaissance des obstacles et des facilitateurs peut guider l'élaboration de stratégies fondées sur des données probantes pour augmenter l'évaluation de la fragilité.