Deprescribing interventions in older adults: An overview of systematic reviews.

OBJECTIVE: The growing deprescribing field is challenged by a lack of consensus around evidence and knowledge gaps. The objective of this overview of systematic reviews was to summarize the review evidence for deprescribing interventions in older adults. METHODS: 11 databases were searched from 1st January 2005 to 16th March 2023 to identify systematic reviews. We summarized and synthesized the results in two steps. Step 1 summarized results reported by the included reviews (including meta-analyses). Step 2 involved a narrative synthesis of review results by outcome. Outcomes included medication-related outcomes (e.g., medication reduction, medication appropriateness) or twelve other outcomes (e.g., mortality, adverse events). We summarized outcomes according to subgroups (patient characteristics, intervention type and setting) when direct comparisons were available within the reviews. The quality of included reviews was assessed using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2). RESULTS: We retrieved 3,228 unique citations and assessed 135 full-text articles for eligibility. Forty-eight reviews (encompassing 17 meta-analyses) were included. Thirty-one of the 48 reviews had a general deprescribing focus, 16 focused on specific medication classes or therapeutic categories and one included both. Twelve of 17 reviews meta-analyzed medication-related outcomes (33 outcomes: 25 favored the intervention, 7 found no difference, 1 favored the comparison). The narrative synthesis indicated that most interventions resulted in some evidence of medication reduction while for other outcomes we found primarily no evidence of an effect. Results were mixed for adverse events and few reviews reported adverse drug withdrawal events. Limited information was available for people with dementia, frailty and multimorbidity. All but one review scored low or critically low on quality assessment. CONCLUSION: Deprescribing interventions likely resulted in medication reduction but evidence on other outcomes, in particular relating to adverse events, or in vulnerable subgroups or settings was limited. Future research should focus on designing studies powered to examine harms, patient-reported outcomes, and effects on vulnerable subgroups. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178860.

Prefabricated Fibula Flap vs Bone-Driven and Delayed Implant Installation for Jaw Reconstruction.

Importance: Restoration of dental occlusion and oral rehabilitation is the ultimate goal of functional jaw reconstruction. Objective: To evaluate the prefabricated fibula flap (PFF) technique in occlusion-driven jaw reconstruction for benign or previously treated malignant disease. Design, Setting, and Participants: This cohort study was conducted from January 2000 to December 2019 at the University of Alberta Hospital and Institute of Reconstructive Sciences in Medicine in Edmonton, Alberta, Canada, among patients who underwent PFF or bone-driven and delayed osseointegrated implant installation (BDD). Patients were followed up for a minimum of 1 year after occlusal rehabilitation. Data were analyzed from July 2021 to June 2022. Exposures: Patients underwent BDD or PFF, which consists of osseointegrated dental implant installation and skin grafting of the fibular bone 3 to 6 months before jaw tumor resection or defect reconstruction. The implant osseointegration is completed at the time of jaw reconstruction, allowing for full reconstruction, loading, and restoration of the dental occlusion in the immediate postoperative period. Main outcomes and Measure: Safety, effectiveness, accuracy, timeliness of occlusal reconstruction, and aesthetic appeal were compared between PFF and BDD. Groups were compared for the following variables: postoperative complications, number of bony segments used, number of procedures needed, total operative time, time to occlusal rehabilitation, and number of implants installed, exposed, lost, and used (ie, exposed implants - lost implants). Aesthetic appeal was assessed using standardized full-face and profile digital photographs taken before and 6 to 12 months after the operation and analyzed by 3 naive raters. Results: Among 9 patients receiving PFF (mean [SD] age, 43.3 [13.0] years; 7 men [77.8%]) and 12 patients receiving BDD (mean [SD] age, 41.9 [18.0] years; 8 men [66.7%]), the overall complication rate was similar (4 patients [44.4%] vs 3 patients [25.0%], respectively; relative risk, 1.78 [95% CI, 0.52 to 6.04]). The number of patients with implant loss was similar between PFF and BDD groups (0 patients vs 3 patients [25.0%], respectively; difference, -25.0 percentage points [95% CI, -48.4 to 9.7 percentage points]). PFF had a clinically meaningful faster mean (SD) occlusal rehabilitation compared with BDD (12.1 [1.9] months vs 60.4 [23.1] months; difference, -48.3 months [95% CI, -64.5 to -32.0 months]). The mean (SD) difference in preoperative to postoperative aesthetic score was similar between PFF and BDD groups (-0.8 [1.5] vs -0.2 [0.8]; difference, -0.6 [95% CI, -1.6 to 0.4]). Conclusions and Relevance: This study found that PFF compared with BDD was a safe, effective, and aesthetic reconstructive option for patients with benign or previously treated jaw malignant tumors. This technique may provide rapid occlusal reconstruction and oral rehabilitation.

A rapid host-protein test for differentiating bacterial from viral infection: Apollo diagnostic accuracy study.

Objectives: To determine the diagnostic accuracy of a rapid host-protein test for differentiating bacterial from viral infections in patients who presented to the emergency department (ED) or urgent care center (UCC). Methods: This was a prospective multicenter, blinded study. MeMed BV (MMBV), a test based on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon gamma-inducible protein-10 (IP-10), and C-reactive protein (CRP), was measured using a rapid measurement platform. Patients were enrolled from 9 EDs and 3 UCCs in the United States and Israel. Patients >3 months of age presenting with fever and clinical suspicion of acute infection were considered eligible. MMBV results were not provided to the treating clinician. MMBV results (bacterial/viral/equivocal) were compared against a reference standard method for classification of infection etiology determined by expert panel adjudication. Experts were blinded to MMBV results. They were provided with comprehensive patient data, including laboratory, microbiological, radiological and follow-up. Results: Of 563 adults and children enrolled, 476 comprised the study population (314 adults, 162 children). The predominant clinical syndrome was respiratory tract infection (60.5% upper, 11.3% lower). MMBV demonstrated sensitivity of 90.0% (95% confidence interval [CI]: 80.3-99.7), specificity of 92.8% (90.0%-95.5%), and negative predictive value of 98.8% (96.8%-99.6%) for bacterial infections. Only 7.2% of cases yielded equivocal MMBV scores. Area under the curve for MMBV was 0.95 (0.90-0.99). Conclusions: MMBV had a high sensitivity and specificity relative to reference standard for differentiating bacterial from viral infections. Future implementation of MMBV for patients with suspected acute infections could potentially aid with appropriate antibiotic decision-making.

Trends in Varenicline Use for Tobacco Cessation, and Their Implications.

BACKGROUND: Tobacco use remains a leading cause of death in the U.S. Varenicline is a preferred medication for tobacco cessation, and a prior report in the literature showed its use fell dramatically after the voluntary recall of Chantix (name-brand varenicline) in July 2021. OBJECTIVES: Working with data on prescriptions for varenicline and nicotine-replacement therapy (NRT), we studied use from 2018 to 2023 to determine if varenicline use had recovered or if there had been a compensatory increase in NRT use. METHODS: Data are yearly from state employees and their dependents who were aged >18 years and were health-insurance beneficiaries of the Washington Public Employees Benefits Board from July 2018 through June 2023. Data include numbers of tobacco users and numbers of prescriptions filled. RESULTS: The 5-year prevalence of tobacco use among 224,816 beneficiaries was 4.6%. The percentage of tobacco users who filled a prescription for varenicline fell from highs of 9.5% and 9.6% in the 2018-2019 and 2019-2020 year to lows of 5.3% and 6.4% in the 2021-2022 and 2022-2023 years. For nicotine replacement therapy, prescriptions rose modestly over the 5 years, from 4.5% in 2018-2019 to 6.0% in 2022-2023. DISCUSSION: Varenicline use dropped after the voluntary recall of Chantix by Pfizer in mid-2021 and has not returned to pre-recall levels. CONCLUSION: Pharmacists and other clinicians should address this drop, in addition to addressing longer-term challenges to increasing varenicline use; these include the requirement for a prescription and the black-box warning by the Food and Drug Administration, rescinded in 2016.

Implementing a Metabolism-Informed Approach for Smoking Cessation in an Alaska Tribal Health System: Study Protocol for a Single-Arm Implementation Pilot Trial.

Background: Individualized treatment for commercial tobacco smoking cessation, such as through the utilization of the nicotine metabolite ratio (NMR), offers substantial clinical benefit. NMR is a metabolism-informed biomarker that can be used to guide medication selection. NMR testing is particularly promising for tobacco cessation efforts in populations with high rates of smoking, such as some Alaska Native and American Indian (AN/AI) communities. To date, no prior study has evaluated the implementation of NMR-guided tobacco cessation with AN/AI populations. Methods: The present "QUIT" protocol is a two-phase study that will occur at Southcentral Foundation (SCF), an Alaska Native-owned health system, serving 70,000 AN/AI people, based in Anchorage, Alaska. In Phase one, qualitative interviews with customer-owners (patients), providers and administrators (n = 36) and a 10-participant beta-test will be used to refine a strategy to implement NMR testing in the health system. Phase two will involve a single-arm pilot trial (n = 50) and qualitative interviews throughout data collection (n = 48) to evaluate the implementation strategy and explore the real-world acceptability and feasibility of NMR testing to guide tobacco cessation with AN/AI populations. Discussion: This study utilizes a community-based participatory approach to refine and implement a nicotine metabolism-informed smoking cessation program in a Tribal healthcare setting. The process and findings from this study will reflect the importance of customer-owner choice and honor the lived experience involved in quitting commercial tobacco. Pilot study data will inform the effect and sample sizes required for a future pragmatic trial of NMR-guided smoking cessation.

Exploring the Impact of the COVID-19 Pandemic on Employees' Workplace Health Promotion Preferences.

PURPOSE: The COVID-19 pandemic has led to profound changes in the workplace as well as increases in stress, missed preventive care, and other health concerns. There is limited research since the onset of the pandemic on employees' primary health concerns and their willingness to engage with workplace health promotion (WHP) programs to address these needs. We conducted this survey about employees' current health priorities as a first step to exploring whether WHP programs need to evolve to be responsive to employees' needs at this stage of the pandemic. DESIGN: National cross-sectional survey. SETTING: United States, April 29-May 5, 2022. SUBJECTS: 2053 Americans employed part or full time. MEASURES: 17-item online survey assessing demographics, health priorities, and impact of the pandemic on health. ANALYSIS: Descriptive statistics, SPSS Version 19. RESULTS: Employees' most common health concerns included work/life balance and stress (each cited by 55%). Nearly half (46%) said their health or well-being was affected by the pandemic; within this group, the most common concerns were stress (66%), anxiety (61%), sleep (49%), and depression (48%). Almost all (94%) indicated they would be open to receiving support from their employers. CONCLUSION: This research is a first step in learning about employees' current health priorities and how they may have changed. WHP researchers and practitioners can determine how their programs align with current priorities. Our future research will explore employees' preferences, heath behaviors, and their current workplace environments in more depth.

Bridging Culture and Language: Encouraging Bilingual/Multicultural Individuals to Act as Information Navigators for Their Loved-Ones and Communities during the COVID-19 Pandemic.

Linguistically diverse communities face barriers to receiving appropriate health information. COVID-19 exacerbated these health-communication inequities. University of Washington researchers surveyed bilingual staff, students, and medical interpreters - desiring training to become effective communicators of COVID-19 information to their social networks and language communities. In response, the COVID-19 Information Navigator Training was developed and pre-tested with professional networks and members of the target audience. The final training comprised three interactive modules and short quizzes. Evaluation surveys measured Information Navigators' confidence in providing COVID-19 information to their social networks. Surveys included questions on the participants' language or cultural community, the perceived value of the training, and their ability to communicate COVID-19 information. Among 393 participants who enrolled in the training, 284 completed the survey. Significant differences in confidence before and after the course were found in detecting COVID misinformation in the news and social media (pre-course mean: 3.83, post-course mean: 4.63; absolute mean difference was 0.82 points higher in the post-evaluation on the 5-point likert scale, 95% CI: 0.70-0.93, p < .01). Training multicultural volunteers to disseminate information to their social networks is a promising strategy for reaching linguistically diverse communities with up-to-date information during health emergencies.

An Antibody-Drug Conjugate Directed to Tissue Factor Shows Preclinical Antitumor Activity in Head and Neck Cancer as a Single Agent and in Combination with Chemoradiotherapy.

Head and neck squamous cell carcinoma (HNSCC) is a solid tumor type that arises in the squamous epithelial cells lining the mucosal surfaces of the upper aerodigestive tract. Long-term survival of patients with advanced disease stage remains disappointing with current treatment options. We show that tissue factor is abundantly expressed on patient-derived HNSCC cell lines, xenograft tumor material, and tumor biopsies from patients with HNSCC. Tisotumab vedotin (TV) is an antibody-drug conjugate (ADC) directed to tissue factor, a protein expressed in many solid tumors. HNSCC cells and xenograft tumors were efficiently eliminated in vitro and in vivo with TV-monotherapy compared with treatment with a control antibody conjugated to monomethyl auristatin E (MMAE). Antitumor activity of TV was also tested in vivo in combination with chemoradiotherapy, standard of care for patients with advanced stage HNSCC tumors outside the oral cavity. Preclinical studies showed that by adding TV to chemoradiotherapy, survival was markedly improved, and TV, not radiotherapy or chemotherapy, was the main driver of antitumor activity. Interestingly, TV-induced cell death in xenograft tumors showed an influx of macrophages indicative of a potential immune-mediated mode-of-action. In conclusion, on the basis of these preclinical data, TV may be a novel treatment modality for patients suffering from head and neck cancer and is hypothesized to improve efficacy of chemoradiotherapy. SIGNIFICANCE: This work shows preclinical in vitro and in vivo antitumor activity of the antibody-drug conjugate Tisotumab vedotin in head and neck cancer models, and enhanced activity in combination with chemoradiotherapy, supporting further clinical development for this cancer type.

Evaluation of the Panbio™ COVID-19 IgG rapid test device performance.

Background: The Panbio™ COVID-19 IgG Rapid Test Device ("Panbio™") detects IgG antibodies against the SARS-CoV-2 spike protein from viral infection or vaccination. Objectives: To determine the diagnostic sensitivity and specificity of the Panbio™ professional use test, using fingerstick whole blood and venous plasma. Study design: Fingerstick whole blood and venous plasma from each participant were tested with Panbio™ and compared against the SARS-CoV-2 IgG II assay on the Abbott Architect™ platform (Europe) or the equivalent AdviseDx SARS-CoV-2 IgG II Abbott Alinity i™ platform (US). 447 evaluable participants were enrolled across 6 US and 9 European clinical centers. Results: For unvaccinated participants with PCR-confirmed infection ≥21 days post-symptom onset, the Panbio™ sensitivity with fingerstick whole blood was 92.6 % (95 % CI: 85.9, 96.7), and the specificity was 97.0 % (95 % CI: 93.1, 99.0). For venous plasma, the sensitivity was 90.0 % (95 % CI: 79.5, 96.2) for participants with PCR-confirmed infection and symptom onset 22-180 days ago; the specificity was 96.3 % (92.2, 98.6). For vaccinated participants, the sensitivity was 98.4 % (95 % CI: 91.2, 100.0) for fingerstick whole blood and 96.7 % (95 % CI: 88.7, 99.6) for venous plasma. Conclusion: The Panbio™ test had high sensitivity and specificity for detecting IgG against the SARS-CoV-2 spike protein.

Simulation-based workshop for emergency preparedness in otolaryngology.

Objectives: This study aimed to evaluate the outcomes of a hands-on simulation-based course with emphasis on procedural techniques, clinical reasoning, and communication skills developed to improve junior Otolaryngology - Head and Neck Surgery (OHNS) residents' preparedness in managing otolaryngologic emergencies. Methods: Junior OHNS residents and faculty from residency programs in California, Nevada, and Arizona participated in this workshop in 2020 and 2021. The stations featured airway management techniques, ultrasound-guided needle aspiration, nasoseptal hematoma evacuation, and facial fracture repair using various models and cadavers. Participants completed a pre-workshop survey, post-workshop survey, and 2-month follow-up survey that assessed resident anxiety and confidence in three OHNS emergency situations across knowledge, manual skills, and teamwork using a 5-point Likert scale. Results: Pre-workshop surveys reported the least anxiety and most confidence in teamwork, but the most anxiety and least confidence in technical skills and knowledge related to foreign body retrieval and airway management. Immediately post-workshop participants reported significant reductions in anxiety and increases in confidence, largest in the manual skills domain, in foreign body retrieval (anxiety: -0.99, confidence: +0.95, p < .01) and airway management stations (anxiety: -0.68, confidence: +1.07, p < .01). Data collected for the epistaxis station showed decreasing confidence and increasing anxiety following the workshop. Conclusion: Our findings demonstrate the effectiveness of a workshop in preparing junior residents in potentially lifesaving otolaryngologic techniques that residents will encounter. Optimizing use of simulation centered training can inform the future of residency education, improving confidence and decreasing anxiety in residents responsible for the safety of patients. Level of Evidence: III.

Sublithospheric diamond ages and the supercontinent cycle.

Subduction related to the ancient supercontinent cycle is poorly constrained by mantle samples. Sublithospheric diamond crystallization records the release of melts from subducting oceanic lithosphere at 300-700 km depths1,2 and is especially suited to tracking the timing and effects of deep mantle processes on supercontinents. Here we show that four isotope systems (Rb-Sr, Sm-Nd, U-Pb and Re-Os) applied to Fe-sulfide and CaSiO3 inclusions within 13 sublithospheric diamonds from Juína (Brazil) and Kankan (Guinea) give broadly overlapping crystallization ages from around 450 to 650 million years ago. The intracratonic location of the diamond deposits on Gondwana and the ages, initial isotopic ratios, and trace element content of the inclusions indicate formation from a peri-Gondwanan subduction system. Preservation of these Neoproterozoic-Palaeozoic sublithospheric diamonds beneath Gondwana until its Cretaceous breakup, coupled with majorite geobarometry3,4, suggests that they accreted to and were retained in the lithospheric keel for more than 300 Myr during supercontinent migration. We propose that this process of lithosphere growth-with diamonds attached to the supercontinent keel by the diapiric uprise of depleted buoyant material and pieces of slab crust-could have enhanced supercontinent stability.

Development and maturation of the occupational health services research field in the United States over the past 25 years: Challenges and opportunities for the future.

Work is an important social determinant of health; unfortunately, work-related injuries remain prevalent, can have devastating impact on worker health, and can impose heavy economic burdens on workers and society. Occupational health services research (OHSR) underpins occupational health services policy and practice, focusing on health determinants, health services, healthcare delivery, and health systems affecting workers. The field of OHSR has undergone tremendous expansion in both definition and scope over the past 25 years. In this commentary, focusing on the US, we document the historical development and evolution of OHSR as a research field, describe current doctoral-level OHSR training, and discuss challenges and opportunities for the OHSR field. We also propose an updated definition for the OHSR field: Research and evaluation related to the determinants of worker health and well-being; to occupational injury and illness prevention and surveillance; to healthcare, health programs, and health policy affecting workers; and to the organization, access, quality, outcomes, and costs of occupational health services and related health systems. Researchers trained in OHSR are essential contributors to improvements in healthcare, health systems, and policy and programs to improve worker health and productivity, as well as equity and justice in job and employment conditions. We look forward to the continued growth of OHSR as a field and to the expansion of OHSR academic training opportunities.

Opportunities to Improve Tobacco Control for State Agency Employees.

OBJECTIVE: The aim of the study is to explore tobacco-related knowledge and perceptions at Washington State (WA) agencies. METHODS: The study used a cross-sectional employee survey and qualitative focus groups with managers/supervisors. We produced descriptive statistics to examine differences in awareness and perceptions of tobacco-control efforts among employees and conducted a rapid thematic analysis of focus group data. RESULTS: Of employees, only 18% with a history of tobacco use had used their agency's cessation benefits. Employees who did not use tobacco and who had higher education had more favorable attitudes toward tobacco-control efforts. In the focus groups, manager/supervisors described limited tobacco cessation promotion at their agency, barriers to tobacco control implementation, and concerns about the perceived effectiveness of additional tobacco-control efforts. CONCLUSIONS: State agencies should increase promotion of tobacco control policies and programs to increase awareness and reduce disparities in tobacco use.

An AI-Enhanced Electronic Health Record Could Boost Primary Care Productivity.

This Viewpoint discusses ways that artificial intelligence (AI) may improve the productivity of primary care physicians with easier and more accurate use of AI-enhanced electronic health records.

Thiamethoxam soil contaminations reduce fertility of soil-dwelling beetles, Aethina tumida.

There in increasing evidence for recent global insect declines. This is of major concern as insects play a critical role in ecosystem functionality and human food security. Even though environmental pollutants are known to reduce insect fertility, their potential effects on insect fitness remain poorly understood - especially for soil-dwelling species. Here, we show that fertility of soil-dwelling beetles, Aethina tumida, is reduced, on average, by half due to field-realistic neonicotinoid soil contaminations. In the laboratory, pupating beetles were exposed via soil to concentrations of the neonicotinoid thiamethoxam that reflect global pollution of agricultural and natural habitats. Emerged adult phenotypes and reproduction were measured, and even the lowest concentration reported from natural habitats reduced subsequent reproduction by 50%. The data are most likely a conservative estimate as the beetles were only exposed during pupation. Since the tested concentrations reflect ubiquitous soil pollution, the data reveal a plausible mechanism for ongoing insect declines. An immediate reduction in environmental pollutants is urgently required if our aim is to mitigate the prevailing loss of species biodiversity.

Age, sex, and survival following ventricular fibrillation cardiac arrest: A mechanistic evaluation of the ECG waveform.

BACKGROUND: Studies of outcome differences by sex in out-of-hospital cardiac arrest (OHCA) have produced mixed results that may depend on age, a potential surrogate for menopausal status. OBJECTIVE: We used quantitative measures of ventricular fibrillation (VF) waveforms - indicators of the myocardium's physiology - to assess whether survival differences according to sex and age group may be mediated via a biologic mechanism. METHODS: We conducted a cohort study of VF-OHCA in a metropolitan EMS system. We used multivariable logistic regression to assess the association of survival to hospital discharge with sex and age group (<55, ≥55 years). We determined the proportion of outcome difference mediated by VF waveform measures: VitalityScore and amplitude spectrum area (AMSA). RESULTS: Among 1526 VF-OHCA patients, the average age was 62 years, and 29% were female. Overall, younger women were more likely to survive than younger men (survival 67% vs 54%, p = 0.02), while survival among older women and older men did not differ (40% vs 44%, p = 0.3). Adjusting for Utstein characteristics, women <55 compared to men <55 had greater odds of survival to hospital discharge (OR = 1.93, 95% CI 1.23-3.09), an association not observed between the ≥55 groups. Waveform measures were more favorable among women and mediated some of the beneficial association between female sex and survival among those <55 years: 47% for VitalityScore and 25% for AMSA. CONCLUSIONS: Women <55 years were more likely to survive than men <55 years following VF-OHCA. The biologic mechanism represented by VF waveform mediated some, though not all, of the outcome difference.

Association Between Facility Surgical Volume and Excess Time in the Hospital After Surgical Resection of Vestibular Schwannomas.

Importance: High surgical vestibular schwannoma case volume in a medical institution may decrease the risk of adverse outcomes among patients undergoing vestibular schwannoma surgery. Objective: To study the association between surgical vestibular schwannoma case volume and excess time in the hospital after vestibular schwannoma surgery. Design, Setting, and Participants: This cohort study evaluated data from the National Cancer Database from January 1, 2004, through December 31, 2019, on Commission on Cancer-accredited facilities in the US. The hospital-based sample comprised adult patients aged 18 years or older with a vestibular schwannoma treated with surgery. Exposures: Facility case volume, defined as the mean number of surgical vestibular schwannoma cases per year in the 2 years preceding the index case. Main Outcomes and Measures: The primary outcome was a composite of prolonged hospital stay (>90th percentile) or 30-day readmission. Risk-adjusted restricted cubic splines were used to model the probability of the outcome according to facility volume. The inflection point (in cases per year) when the declining risk of excess time in the hospital began to plateau was selected as the threshold to define high- and low-volume facilities. Outcomes were compared among patients treated at high- and low-volume facilities, with mixed-effects logistic regression models adjusting for patient sociodemographic characteristics, comorbidities, tumor size, and clustering within facilities. Collected data were analyzed between June 24 and August 31, 2022. Results: Among 11 524 eligible patients (mean [SD] age, 50.2 [12.8] years; 53.5% female; 46.5% male) who underwent surgical resection of vestibular schwannoma at 66 reporting facilities, the median length of stay was 4 (IQR, 3-5) days, and 655 patients (5.7%) were readmitted within 30 days. The median case volume was 16 (IQR, 9-26) cases per year. An adjusted restricted cubic spline model identified a downtrending probability of excess time in the hospital with increasing volume. The declining risk of excess time in the hospital began to plateau at a facility volume of 25 cases per year. Surgery at a facility with an annual case volume at or above this threshold was independently associated with a 42% reduction in the odds of excess time in the hospital compared with surgery at a low-volume center (odds ratio, 0.58; 95% CI, 0.44-0.77). Conclusions and Relevance: This cohort study found that among adults undergoing vestibular schwannoma surgery, a higher facility case volume was associated with a reduced risk of prolonged hospital stay or 30-day readmission. A facility case volume of 25 cases per year may represent a risk-defining threshold.

Systematic study of tissue factor expression in solid tumors.

BACKGROUND: Elevated tissue factor (TF) expression, although restricted in normal tissue, has been reported in multiple solid cancers, and expression has been associated with poor prognosis. This manuscript compares TF expression across various solid tumor types via immunohistochemistry in a single study, which has not been performed previously. AIMS: To increase insight in the prevalence and cellular localization of TF expression across solid cancer types, we performed a detailed and systematic analysis of TF expression in tumor tissue obtained from patients with ovarian, esophageal, bladder, cervical, endometrial, pancreatic, prostate, colon, breast, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and glioblastoma. The spatial and temporal variation of TF expression was analyzed over time and upon disease progression in patient-matched biopsies taken at different timepoints. In addition, TF expression in patient-matched primary tumor and metastatic lesions was also analyzed. METHODS AND RESULTS: TF expression was detected via immunohistochemistry (IHC) using a validated TF-specific antibody. TF was expressed in all cancer types tested, with highest prevalence in pancreatic cancer, cervical cancer, colon cancer, glioblastoma, HNSCC, and NSCLC, and lowest in breast cancer. Staining was predominantly membranous in pancreatic, cervical, and HNSCC, and cytoplasmic in glioblastoma and bladder cancer. In general, expression was consistent between biopsies obtained from the same patient over time, although variability was observed for individual patients. NSCLC biopsies of primary tumor and matched lymph node metastases showed no clear difference in TF expression overall, although individual patient changes were observed. CONCLUSION: This study shows that TF is expressed across a broad range of solid cancer types, and expression is present upon tumor dissemination and over the course of treatment.

What happens in Vegas, stays in your lungs: an assessment of fine particulate matter in casinos that prohibit and allow smoking in Las Vegas, Nevada, USA.

INTRODUCTION: Despite progress in adoption of smoke-free policies, smoking in casinos is allowed in some US states, including Nevada. In 2020, for the first time, a resort-style casino in Las Vegas prohibited smoking voluntarily. This study is the first to assess air quality in this casino and compare results with similar casinos that allow smoking. METHODS: A real-time personal aerosol monitor evaluated particulate matter with a diameter <2.5 µm (PM2.5), a surrogate for secondhand smoke (SHS). PM2.5 was measured at eight Las Vegas casinos, including the smoke-free casino. Each casino was visited twice, and PM2.5 was assessed in smoking-permitted gaming areas and areas where smoking is otherwise prohibited. RESULTS: Average PM2.5 levels were significantly higher in casinos that allow smoking, for both casino gaming areas and areas where smoking is otherwise prohibited (p<0.05). Mean PM2.5 in gaming areas was 164.9 µg/m3 in casinos that allow smoking and 30.5 µg/m3 in the smoke-free casino. Mean PM2.5 in areas where smoking is otherwise prohibited was 83.2 µg/m3 in casinos which allowed smoking in gaming areas, and 48.1 µg/m3 in the smoke-free casino. CONCLUSION: Despite robust evidence about the harms of SHS, tens of thousands of casino employees and tens of millions of tourists are exposed to high levels of SHS in Las Vegas casinos annually, with PM2.5 levels 5.4 times higher in gaming areas when compared with a smoke-free casino. The only way to protect people from SHS exposure is to prohibit smoking in all indoor areas.

Extreme redox variations in a superdeep diamond from a subducted slab.

The introduction of volatile-rich subducting slabs to the mantle may locally generate large redox gradients, affecting phase stability, element partitioning and volatile speciation1. Here we investigate the redox conditions of the deep mantle recorded in inclusions in a diamond from Kankan, Guinea. Enstatite (former bridgmanite), ferropericlase and a uniquely Mg-rich olivine (Mg# 99.9) inclusion indicate formation in highly variable redox conditions near the 660 km seismic discontinuity. We propose a model involving dehydration, rehydration and dehydration in the underside of a warming slab at the transition zone-lower mantle boundary. Fluid liberated by dehydration in a crumpled slab, driven by heating from the lower mantle, ascends into the cooler interior of the slab, where the H2O is sequestered in new hydrous minerals. Consequent fractionation of the remaining fluid produces extremely reducing conditions, forming Mg-end-member ringwoodite. This fractionating fluid also precipitates the host diamond. With continued heating, ringwoodite in the slab surrounding the diamond forms bridgmanite and ferropericlase, which is trapped as the diamond grows in hydrous fluids produced by dehydration of the warming slab.