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This paper reports an experimental study of tip vortex flowfield and cavitation inception of a tip-loaded hydrofoil. Vortex strength, wandering, and turbulence statistics are characterized using stereo particle image velocimetry (SPIV) in a water tunnel facility, at a chord Reynolds number of 1.3×106. Cavitation physics are characterized using high-speed videography and dual-hydrophone acoustic cavitation measurements. The loading of the rectangular planform hydrofoil has a maximum at 65% span, 56% greater than that at the root, i.e., the hydrofoil loading is representative of non-elliptically loaded open propellers. Acoustic cavitation inception is quantified and is observed to precede visual cavitation onset using unaided and high-speed imaging. Measurements reported here show that vorticity fluctuations are nearly of the same magnitude as the ensemble vorticity. Instantaneous measurements of vorticity at the trailing edge, 12-chord downstream, and one-chord downstream positions are reported. Their peak magnitudes are located adjacent to the ensemble vortex center and are between four and five times the ensemble mean. The fluctuating vorticity measurements, taken in conjunction with high-speed video observations, provide insight into the hydrodynamic conditions responsible for intermittent cavitation events. The reported measurements elucidate instantaneous and mean turbulence physics associated with vortex cavitation and can provide a validation basis for numerical simulations.

New treatments, particularly second-line options, are needed to improve outcomes for patients with recurrent/metastatic cervical cancer (r/mCC). Tisotumab vedotin (TV) is an antibody-drug conjugate directed to tissue factor, a transmembrane protein commonly expressed in cancer cells, to deliver cytotoxic monomethyl auristatin E. This single-arm, open-label phase 1/2 trial evaluated the consistency of safety and efficacy outcomes of TV in Japanese patients with r/mCC to bridge the current findings with those reported in previous trials in non-Japanese patients in the United States and Europe. In part 1 (dose escalation; N = 6), patients with advanced solid tumors received TV 1.5 or 2.0 mg/kg once every 3 weeks to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Part 2 (dose expansion; N = 17) evaluated the RP2D in r/mCC patients with 1-2 prior lines of therapy. In part 1, no dose-limiting toxicities were observed, the MTD was not reached, and TV 2.0 mg/kg was established as the RP2D. In part 2, the most common treatment-emergent adverse events were anemia (58.8%), nausea (58.8%), alopecia (47.1%), epistaxis (47.1%), and diarrhea (35.3%); adverse events of special interest were bleeding (76.5%), ocular events (35.3%), and peripheral neuropathy (17.6%), and were mostly grade 1/2. In part 2, confirmed objective response rate was 29.4%, median duration of response was 7.1 months, and median time to response was 1.2 months. In Japanese patients with r/mCC, TV demonstrated a manageable and tolerable safety, pharmacokinetics, and efficacy profile consistent with that observed in non-Japanese patients.

Supplementary Data

Purpose:Tissue factor (TF) is a potential target in cervical cancer, as it is frequently highly expressed and associated with poor prognosis. Tisotumab vedotin, a first-in-class investigational antibody–drug conjugate targeting TF, has demonstrated encouraging activity in solid tumors. Here we report data from the cervical cancer cohort of innovaTV 201 phase I/II study (NCT02001623).Patients and Methods:Patients with recurrent or metastatic cervical cancer received tisotumab vedotin 2.0 mg/kg every 3 weeks until progressive disease, unacceptable toxicity, or consent withdrawal. The primary objective was safety and tolerability. Secondary objectives included antitumor activity.Results:Of the 55 patients, 51% had received ≥2 prior lines of treatment in the recurrent or metastatic setting; 67% had prior bevacizumab + doublet chemotherapy. Fifty-one percent of patients had squamous cell carcinoma. The most common grade 3/4 treatment-emergent adverse events (AEs) were anemia (11%), fatigue (9%), and vomiting (7%). No grade 5 treatment-related AEs occurred. Investigator-assessed confirmed objective response rate (ORR) was 24% [95% confidence interval (CI): 13%−37%]. Median duration of response (DOR) was 4.2 months (range: 1.0+−9.7); four patients responded for >8 months. The 6-month progression-free survival (PFS) rate was 29% (95% CI: 17%−43%). Independent review outcomes were comparable, with confirmed ORR of 22% (95% CI: 12%−35%), median DOR of 6.0 months (range: 1.0+−9.7), and 6-month PFS rate of 40% (95% CI: 24%−55%). Tissue factor expression was confirmed in most patients; no significant association with response was observed.Conclusions:Tisotumab vedotin demonstrated a manageable safety profile and encouraging antitumor activity in patients with previously treated recurrent or metastatic cervical cancer.

Background Mutations involving BRAF and TERT are important predictors of disease severity in thyroid cancer, but molecular testing is limited by cost and lack of adequate tissue sample. This study aimed to assess the utility of BRAFV600E and TERT testing using droplet digital PCR (ddPCR) as a diagnostic and prognostic tool for thyroid fine needle aspirate biopsy (FNAB). Methods Patients with thyroid nodules were prospectively enrolled from March 2015 to September 2018. Pre-operative FNAB was collected for standard cytology and molecular testing. BRAFV600E and TERT levels were analyzed by ddPCR. Cytology (Bethesda system) and ddPCR results were correlated to surgical pathology. Results A total of 222 patients were enrolled, of which 124 received thyroid surgery. Pre-operative cytology alone with Bethesda ≥5 was 100% specific and 70% sensitive for malignancy on final surgical pathology. BRAFV600E positivity or TERT overexpression was 100% specific and 60.0% sensitive. Combining cytology (Bethesda ≥5) with BRAFV600E and TERT testing increased the sensitivity of a malignant diagnosis to 80.0%. High TERT levels and/or BRAFV600E was associated with aggressive or advanced stage pathology. Conclusions Combining cytology with ddPCR analysis of BRAFV600E and TERT can improve the diagnostic accuracy of thyroid FNAB, and help predict aggressive pathology.

The annual number of firearm injuries in Portland, Oregon has been higher in the years since 2020 than in any prior year in the city's history. This descriptive study analyzed data from Gun Violence Archives (GVA) from January 1, 2018, to December 31, 2021. All incidents in GVA of interpersonal firearm injury that occurred in Portland during this period were analyzed for location, number of people injured or killed, and demographic information for those injured or killed. Comparisons in firearm injury rates were made with Seattle and San Francisco. Interpersonal firearm injuries began to rise after the first COVID-19 case in Oregon; July 2020 had the most injuries in the four-year period. Black men suffered the highest rate of interpersonal fatalities, with more than 11-fold higher rate per 100,000 than White men in every year studied. Portland had a higher rate of total interpersonal firearm injuries and a higher rate of firearm fatalities from 2018 through 2021 compared to Seattle and San Francisco. Neighborhoods near Downtown and those on the Eastside of the city had the highest rates of interpersonal injuries and deaths from firearms, whereas those in the Southwest had the lowest. Defining the burden of disease from interpersonal firearm injuries is a fundamental step in designing future public health research and implementing interventions to curb the trauma brought by interpersonal firearm injury.

Background: Rigorous evidence to guide deprescribing is limited, and priorities to inform deprescribing research and practice remain unclear. The objective of this overview of systematic reviews (i.e. reviews) was to synthesize the available review evidence regarding the effectiveness of interventions to deprescribe medications in older adults. Methods 11 databases were searched from January 2005 to October 2020. We included randomized or non-randomized controlled designs. Two independent reviewers screened and extracted data. We synthesized results in two steps: Step 1 identified results as reported by the original review (including meta-analyses) and Step 2 involved a narrative synthesis of reviews by outcome. Pre-specified subgroups included patient characteristics (e.g., dementia, frailty, advanced age), intervention type and setting. Outcomes included medication-related outcomes (e.g., medication reduction, potentially inappropriate medications) or other outcomes(e.g., mortality, adverse effects, falls, cognition, hospitalizations, quality of life, costs, surrogate biomarkers). Assessment of Multiple Systematic Reviews 2 was used to assess quality of reviews. RESULTS: 2,335 unique citations were retrieved, of which 93 full-text articles were assessed for eligibility. 33 reviews (encompassing 13 meta-analyses) were included. 19 of the 33 reviews had a general deprescribing focus, 13 focused on specific medication classes or therapeutic category and one review included both. Ten of 13 reviews meta-analyzed medication-related outcomes (29 outcomes: 21 favored the intervention, seven reported no difference and one favored the comparison). The narrative synthesis indicated that most interventions resulted in some evidence of medication reduction. Few meta-analyses reported on other outcomes, and our narrative synthesis found primarily mixed effects or no evidence of an effect on these outcomes. Limited information was available for patient characteristic subgroups. All reviews scored low or critically low on quality assessment. CONCLUSIONS: Deprescribing interventions likely resulted in medication reduction. Information about other outcomes was not routinely examined, and where included, studies were likely underpowered. The evidence, though of low quality, suggests deprescribing was not associated with increased adverse events, and had little evidence of effect on mortality, quality of life and health-care use. Future research should focus on designing studies powered to examine harms, patient-centered outcomes and the effects on vulnerable subgroups. Systematic Review Registration PROSPERO CRD42020178860 This study was supported by NIA (1R24AG064025).

Background The tongue is an essential organ for human interaction, communication and survival. To date, there is a paucity of objective functional, patient reported, or quality of life outcomes of patients undergoing a total glossectomy with preservation of the larynx (TGLP). Objective To examine prospectively collected objective, self‐reported functional and quality of life (QOL) data in patients undergoing TGLP and free flap reconstruction. Methods Sixteen TGLP patients were identified in the prospective head and neck cancer and functional outcomes database between January of 2009 and December 2017. Data collection included patient age, sex, performance status, TNM staging, diagnosis and adjuvant treatment. Swallowing and speech functions were measured and prospectively recorded pre‐ and postoperatively. Patient reported outcomes were measured with the Speech Handicap Index (SHI) and the M.D. Anderson Dysphagia Inventory (MDADI). Results All patients had a significant reduction in their objective swallowing (P = 0.035), sentence (P = 0.001) and word intelligibility (P

Objective To examine local health department (LHD) contexts, capacity for, and interest in partnering with employers on workplace health promotion programs (WHPPs) for chronic disease prevention. Design Qualitative interviews with LHD directors. Setting LHDs from 21 counties in 10 states. Participants Twenty-one LHD directors. Main outcome measures(s) Experiences and perceptions of existing partnerships, decision making, funding, data needs, and organizational capacity for WHPP partnerships with employers. Results We identified 3 themes: (1) LHDs see the value of partnering with employers but lack the capacity to do so effectively; (2) while LHDs base priorities on community need, funding ultimately drives decision making; and (3) rural, micropolitan, and urban LHDs differ in their readiness and capacity to work with employers. Conclusions Understanding LHDs' partnership capacity and context is essential to the successful implementation of WHPP partnerships with employers. Expanding these partnerships may require additional financial investments, particularly among rural LHDs.

Most US businesses are small, yet they employ almost half of the nation's workforce. Literature is limited about how small employers (those with 20-250 employees) have made decisions about operating their businesses during the COVID-19 pandemic. We sought to learn how employers made these decisions, what information sources they used, what information they wanted, and to what extent they worked with or used information from their local health department.We conducted qualitative, semistructured interviews with 26 employers in Washington State, from August through October 2020. Employers were recruited from 7 counties (4 urban and 3 rural) that were experiencing either higher or lower COVID-19 case rates than Washington State overall.Employers relied heavily on national government resources to make decisions about how to operate their businesses during the COVID-19 pandemic. Few employers had relationships with or turned to their local health departments for information or support. Employers wanted information about COVID-19 safety that was specific to their business operations and industry. Employers also described the emotional toll of COVID-19 and the challenge of trying to make high-stakes decisions with rapidly evolving information.Small employers showed little awareness of their local health departments and the information and assistance they could provide. Local health departments could increase their visibility and build relationships with small employers by partnering with them on value-added services such as workplace health promotion. Establishing these relationships could support more rapid collaboration between local health departments and small employers during future public health crises.

Purpose This study examined the relationship between employee outcomes and employer implementation of evidence-based interventions (EBIs) for chronic disease prevention. Design Cross-sectional samples collected at 3 time points in a cluster-randomized, controlled trial of a workplace health promotion program to promote 12 EBIs. Setting King County, WA. Sample Employees of 63 small, low-wage workplaces. Measures Employer EBI implementation; 3 types of employee outcomes: perceived implementation of EBIs; perceived employer support for health; and health-related behaviors, perceived stress, depression risk, and presenteeism. Analysis Intent-to-treat and correlation analyses using generalized estimating equations. We tested bivariate associations along potential paths from EBI implementation, through perceived EBI implementation and perceived support for health, to several employee health-related outcomes. Results The intent-to-treat analysis found similar employee health-related behaviors in intervention and control workplaces at 15 and 24 months. Workplaces implemented varying combinations of EBIs, however, and bivariate associations were significant for 4 of the 6 indicators of physical activity and healthy eating, as well as perceived stress, depression risk, and presenteeism. We did not find significant positive associations for cancer screening and tobacco cessation. Conclusion Our findings support broader dissemination of EBIs for physical activity and healthy eating, as well as more focus on improving employer support for employee health. They also suggest we need better interventions for cancer screening and tobacco cessation.

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. ispartof: CANCER REPORTS vol:6 issue:2 ispartof: location:United States status: published

IntroductionDespite 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.MethodsA real-time personal aerosol monitor evaluated particulate matter with a diameter ResultsAverage PM2.5 levels were significantly higher in casinos that allow smoking, for both casino gaming areas and areas where smoking is otherwise prohibited (p3in casinos that allow smoking and 30.5 µg/m3in the smoke-free casino. Mean PM2.5 in areas where smoking is otherwise prohibited was 83.2 µg/m3in casinos which allowed smoking in gaming areas, and 48.1 µg/m3in the smoke-free casino.ConclusionDespite 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.

Background Fine needle aspiration (FNA) is a common diagnostic tool used in the initial evaluation of parotid masses. In the literature, variable diagnostic accuracy of FNA is reported. Therefore, when considering clinical management of these patients, the utility of FNA is unclear. The aim of this study was to determine the capability of ultrasound-guided FNA to differentiate between benign and malignant neoplasms. Further, the way in which FNA results affect clinical decision-making was assessed. Methods Retrospective data were collected for all patients who underwent parotidectomy at a large Canadian tertiary care center between 2011 and 2016. Patient demographics, preoperative imaging reports, preoperative FNA results, and final pathological diagnosis were analyzed. Results Of the 199 patients who underwent parotidectomy, 184 had preoperative ultrasound-guided FNA. There were a total of 13 non-diagnostic FNAs. In diagnosing malignancy, FNA had a sensitivity and specificity of 71.4% and 98.7%, respectively. The positive predictive value (PPV) was 83.3%. The negative predictive value was 97.5%. Of the non-diagnostic FNAs, 2 out of 13 (15.4%) were deemed malignant neoplasms on final pathology. Conclusion FNA is a useful adjunct in the work-up of parotid masses, but it should be used with caution. Due to limited sensitivity, it should not be relied upon as the sole determinant of a surgeon’s management plan.

Background Evidence-based interventions (EBIs) for tobacco control can be implemented in worksite settings to reduce tobacco use. Small worksites are less likely to adopt tobacco control EBIs than large worksites. The purpose of this qualitative study was to 1) explore factors that impact small employers’ decisions to offer tobacco control EBIs, and 2) understand employees’ perceptions of tobacco control at small worksites. Methods Working with staff from small worksites (20–250 employees), we analyzed data from 12 semi-structured interviews with employers (via key informants) and four focus groups with employees. We recruited employers and employees through a purchased business list and market research company, respectively. Interview and focus group topics included perceptions of worksite tobacco control; internal and external forces shaping worksite tobacco control implementation; and perceived worksite support for cessation. We conducted thematic data analysis. Results Key themes from the employer interviews included: the local environment played an important role in implementation of tobacco control EBIs; tobacco control was perceived as important but not a priority; and tobacco control decisions were driven by worksite culture. Key themes from the employee focus groups included: perceived employer support for tobacco cessation was limited although there was interest from employees; employees who currently used tobacco were stigmatized for their behavior; and incentives and coaching were considered ideal tobacco control EBIs. Conclusions Tobacco control has not been prioritized at small worksites, despite employees welcoming additional cessation support. This study contributes important information on contextual factors and employee preferences that could be targeted to improve tobacco control EBI implementation. Worksites should implement comprehensive tobacco-free policies, minimize stigma when promoting cessation, establish equitable break policies, and involve employees in decision-making related to tobacco control.

Context: Worksites can serve as community sites for local health jurisdictions (LHJs) to assist with implementation of evidence-based interventions (EBIs) to prevent and control chronic diseases. Objective: To assess the feasibility and effectiveness of using LHJ staff to disseminate Connect to Wellness (CtW), an effective dissemination package for increasing implementation of EBIs for chronic disease control by small worksites. Design: Single-arm, multisite intervention trial, with measurement at baseline, after 6 months of intervention, and after a maintenance period of 6 months. Setting: Six geographically dispersed counties in Washington State. Target worksites had 20 to 250 employees. Participants: Nine staff members from 6 LHJs delivered CtW to 35 worksites. Intervention: Connect to Wellness seeks to increase worksites' implementation of 14 EBIs classified as communication, policy, or program approaches to increasing 4 behaviors: cancer screening, healthy eating, physical activity, and tobacco cessation. Main Outcome Measure: Evidence-based intervention implementation measured on a scale from 0% to 100%. Results: Participating worksites showed a significant increase (P < .001, t test) in total mean implementation scores from baseline (33%) to 6-month follow-up (47%). Increases in implementation for communications, policy, healthy eating, and tobacco EBIs were statistically significant at 6 months and maintained at 12 months. Increased implementation at 6 months of a group physical activity program was not sustained after the program became unavailable, and total implementation scores at 12 months (38%) showed little change from baseline. Conclusions: Local health jurisdiction–delivered CtW increased worksites' implementation of EBIs at 6 months, and increased implementation in communication, policy, healthy eating, and tobacco was maintained at 12 months. This package, delivered by LHJ staff working part-time on CtW, was nearly as successful as prior delivery by staff working full-time on CtW.

Objective The total oral tongue (anterior 2/3 glossectomy) defect is seldom addressed in the literature. This is the first series to describe a consistent technique for its reconstruction. The aim of the study is to describe the use of the beavertail modified radial forearm free flap (BTRFFF) to reconstruct a total oral tongue defect and the functional and quality of life outcomes associated with it. Study design Retrospective review of prospectively collected data from 2000 to 2010. Methods All patients at the University of Alberta undergoing head and neck free flap surgery are enrolled in a prospective functional outcomes program. Pre-operatively and at set post-operative time points patients complete videofluoroscopic swallowing studies (VFSS), speech evaluations and quality of life questionnaires (EORTC H&N-35). Peri-operative outcomes were also measured. Results 17 consecutive patients were included. All were gastrostomy tube free at 12 months post-operatively and tolerating a full soft diet with aspiration scores of 0. Swallowing transit times increased by a mean of 0.4 s (p = 0.32). Speech intelligibility remained high with mean sentence intelligibility at 75% and single word intelligibility at 62%. Quality of life scores returned to baseline and remained satisfactory. Complications related to the BTRFFF were limited to scarring. Conclusions The BTRFFF provides a robust reconstructive option for the total oral tongue defect with excellent long term functional outcomes and quality of life.

Objectives: To describe how physical therapy providers and their patients interact and communicate about physical activity (PA), and explore the barriers and facilitators to patient involvement in PA programs. Method: We conducted 39 direct observations of patient visits with physical therapy providers and 30 telephone interviews with physical therapists (PTs). We conducted a thematic analysis of observation field notes and interview transcripts. Results: PTs and patients engaged in several behaviors to build rapport, discussed PA type and frequency, and exchanged advice and information about PA. Barriers to patient participation in PA programs included low instrumental support, physical limitations, lack of motivation and confidence, and lack of knowledge about available programs. Facilitators included emotional support from friends, peers, and family, and encouragement and information-sharing from providers. Discussion: PTs play an important role in improving older adult PA and could be instrumental in reducing barriers to PA participation.

Background The role of molecular biomarkers in oropharyngeal squamous cell carcinoma (OPSCC) has recently been increasingly recognized. There is conflicting evidence in the literature with regards to the prognostic value of p53 and Bcl-xL. Objective The purpose of this study was to investigate the association between p53 and Bcl-xL expression profiles and survival outcomes in OPSCC. Methods Patients diagnosed with OPSCC and treated with curative intent between 1998 and 2009 were included in the study. Patient demographics, disease, treatment, and oncologic outcomes were collected prospectively. A tissue microarray (TMA) from patients' biopsies or surgical specimens was retrospectively constructed. The expression levels of p53, Bcl-xL, and p16 were digitally quantified and correlated to patient survival outcomes. Results One hundred and sixty-six patients were included (mean age 56.7 years; standard deviation (SD) ± 10.0; 78% male). High expression of Bcl-xL (p= 0.04) was significantly associated with nodal disease at presentation, and decreased overall survival (OS) (p= 0.04). Combined expression of low Bcl-xL and low p53 conferred a survival advantage in non-smokers (p= 0.04). Multivariate analysis supported smoking and p16 status as independent prognosticators for OS. Conclusions This study suggests that biomarker profiling using Bcl-xL and p53 levels may be of prognostic value in select patients with OPSCC.

Summary Background Few effective second-line treatments exist for women with recurrent or metastatic cervical cancer. Accordingly, we aimed to evaluate the efficacy and safety of tisotumab vedotin, a tissue factor-directed antibody–drug conjugate, in this patient population. Methods This multicentre, open-label, single-arm, phase 2 study was done across 35 academic centres, hospitals, and community practices in Europe and the USA. The study included patients aged 18 years or older who had recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer; disease progression on or after doublet chemotherapy with bevacizumab (if eligible by local standards); who had received two or fewer previous systemic regimens for recurrent or metastatic disease; had measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1); and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 2·0 mg/kg (up to a maximum of 200 mg) tisotumab vedotin intravenously once every 3 weeks until disease progression (determined by the independent review committee) or unacceptable toxicity. The primary endpoint was confirmed objective response rate based on RECIST (version 1.1), as assessed by the independent review committee. Activity and safety analyses were done in patients who received at least one dose of the drug. This study is ongoing with recruitment completed and is registered with ClinicalTrials.gov, NCT03438396. Findings 102 patients were enrolled between June 12, 2018, and April 11, 2019; 101 patients received at least one dose of tisotumab vedotin. Median follow-up at the time of analysis was 10·0 months (IQR 6·1–13·0). The confirmed objective response rate was 24% (95% CI 16–33), with seven (7%) complete responses and 17 (17%) partial responses. The most common treatment-related adverse events included alopecia (38 [38%] of 101 patients), epistaxis (30 [30%]), nausea (27 [27%]), conjunctivitis (26 [26%]), fatigue (26 [26%]), and dry eye (23 [23%]). Grade 3 or worse treatment-related adverse events were reported in 28 (28%) patients and included neutropenia (three [3%] patients), fatigue (two [2%]), ulcerative keratitis (two [2%]), and peripheral neuropathies (two [2%] each with sensory, motor, sensorimotor, and neuropathy peripheral). Serious treatment-related adverse events occurred in 13 (13%) patients, the most common of which included peripheral sensorimotor neuropathy (two [2%] patients) and pyrexia (two [2%]). One death due to septic shock was considered by the investigator to be related to therapy. Three deaths unrelated to treatment were reported, including one case of ileus and two unknown causes. Interpretation Tisotumab vedotin showed clinically meaningful and durable antitumour activity with a manageable and tolerable safety profile in women with previously treated recurrent or metastatic cervical cancer. Given the poor prognosis for this patient population and the low activity of current therapies in this setting, tisotumab vedotin, if approved, would represent a new treatment for women with recurrent or metastatic cervical cancer. Funding Genmab, Seagen, Gynaecologic Oncology Group, and European Network of Gynaecological Oncological Trial Groups.

OBJECTIVE To contribute to a broader understanding of effective implementation strategies to help managers engage employees in workplace wellness. METHODS We beta-tested an online training at four Washington state agencies (two test, two control). We administered a post-training evaluation, re-administered an online manager survey and conducted additional interviews with wellness leads. RESULTS Training participation rate was high. The two test agencies experienced a significant increase in the percentage of managers who: agreed that they received training on employee wellness; agreed their agency's culture supports employee wellness; and encouraged their employees to participate in wellness activities. Approximately 80% of managers who received the training agreed they could apply information learned to support employee wellness. CONCLUSIONS If proven effective, the training could be administered at a low cost and disseminated to improve employee health.

Jaw defect reconstructions have been transformed by the development of free tissue transfer using vascularized bone incorporating osseointegrated dental implants. We recently developed a modification our method this procedure and termed it the Modified Alberta Reconstruction Technique (MART). The objective of this study aimed to assess the soft tissue component and outcomes of the MART as compared to the Alberta Reconstructive Technique (ART) or conventional (BDD) reconstructions.This was a prospective cohort study of adult patients who underwent jaw reconstruction with dental implant rehabilitation between 2000 and 2019 in Edmonton, Alberta. Patients were aged-matched and placed into a cohort based on the type of reconstruction they received. Outcomes were compared between the groups. Expert and aesthetic analyses were performed. Statistical analysis was conducted to determine significance.A total of 46 patients (15 BDD, 15 ART and 16 MART) were included. Demographics were similar between groups. There was no difference in complications. The soft tissue component of the MART cohort was more favourable to work with as judged by the occlusal reconstructive experts. The MART was rated as more aesthetically appealing in comparison to the BDD and ART (p = 0.049).The MART is a safe, effective, and aesthetically appealing procedure. It yields a good functional result and a clinically better soft tissue component for occlusal reconstructions. For a select group of patients requiring jaw reconstruction, the MART is an ideal reconstructive option as the modification provides good control of the soft tissue around the implants.

Background Tisotumab vedotin (TV) is an investigational antibody-drug conjugate composed of a tissue factor (TF)-directed human monoclonal antibody covalently linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable linker. TV demonstrated single agent activity (24% objective response rate [ORR]) in previously treated recurrent or metastatic cervical cancer (NCT03438396) where currently, there is no standard of care and ORRs are typically less than 15% and often of limited duration.1–8 TV is currently being evaluated in combination with pembrolizumab (PD-1 inhibitor), bevacizumab, or carboplatin in cervical cancer (NCT03786081), or as a monotherapy in multiple other solid tumors (NCT03913741, NCT03485209, NCT03657043). The anti-tumor activity of TV may be multimodal as TV can induce tumor cell death through several mechanisms, including direct and bystander MMAE-mediated cytotoxicity, as well as antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and immunogenic cell death (ICD)].9 10 To better characterize immune-mediated tumor cell killing by TV and further the rationale for combination with pembrolizumab, we set out to refine our understanding of TV-mediated ICD and subsequent immunomodulatory effects. Methods We evaluated the ability of TV to mediate activation of immune cells in vitro using co-cultures of TF-expressing tumor cells and human peripheral blood mononuclear cells (PBMCs). We also assessed the ability of TV to induce recruitment of innate immune cells to tumors in vivo using a TF-expressing xenograft tumor model. Results In vitro, tumor cells treated with TV showed several hallmarks of immunogenic cell death, including markers of endoplasmic reticulum (ER) stress and release of ATP and high mobility group protein B1 (HMGB1). Co-culture of TV-killed tumor cells with allogeneic human PBMCs led to innate immune cell activation (measured by upregulation of the costimulatory molecule CD86) and T cell proliferation. Combination with PD-1 blockade further amplified the immune response, leading to enhanced T cell proliferation and cytokine production. Moreover, in vivo studies demonstrated that TV treatment led to recruitment of F4/80+ and CD11c+ innate immune cells to xenograft tumors. Conclusions These data show that, in preclinical models, TV induces immunogenic tumor cell death, which can promote activation and recruitment of immune cells to the tumor. The totality of in vitro and in vivo data provides evidence for the immunomodulatory effects of TV and bolsters rationale for combining TV with immune checkpoint agents. Ongoing analyses aim at further characterizing the immune response induced by TV in preclinical models and patients. Acknowledgements We would like to thank Kristen Gahnberg for embedding and sectioning tissues for these studies and Anthony Cao for his early work identifying hallmarks of ICD in response to TV treatment in vitro.9 Ethics Approval Animals studies were approved by and conducted in accordance with Seattle Genetics Institutional Care and Use Committee protocol #SGE-029. Consent N/A References Van den berg YW, Osanto S, Reitsma PH, Versteeg HH. The relationship between tissue factor and cancer progression: insights from bench and bedside. Blood 2012;119(4):924–932. Miller DS, Blessing JA, Bodurka DC, Bonebrake AJ, Schorge JO. 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Purpose: Small employers, while motivated to implement wellness programs, often lack knowledge and resources to do so. As a result, these firms rely on external decision-making support from insurance brokers. The objective of this study was to analyze brokers’ familiarity with wellness programs and to characterize their role and interactions with small employers. Design: Using a newly developed common interview guide (20 questions), protocol and analysis plan, 20 interviews were conducted with health insurance brokers in Illinois, Minnesota, North Carolina and Washington in 2016 and 2017. In addition to exploring patterns of broker interactions and familiarity by segment, we propose a framework to conceptualize the broker-client relationship using social capital theory and the RE-AIM model. Methods: Interviews were transcribed, summarized and a common codebook was established using DeDoose. Themes were identified following multi-rater coding and structured within the framework. Results: Participating brokers reported having a high to moderate familiarity with wellness programs (65%) and a majority (80%) indicated that they have previously advised their small business clients on the availability and features of them. Further, we find that brokers may help eliminate barriers to resources and act as a connector to wellness opportunities within their professional network. Conclusion: New initiatives to promote small employer wellness programs can benefit from examining the influence of brokers on the decision-making process. When engaged and supported with resources, brokers may be effective champions for employer wellness programs.

Purpose: To examine the reliability and validity of a brief measure (the Workplace Support for Health [WSH] scale) to assess employees’ perceived support for a healthy lifestyle. Design: Repeated cross-sectional surveys. Setting: We collected employer- and employee-level survey data from small, low-wage workplaces in King County, WA enrolled in a randomized controlled trial. Sample: We analyzed data from 68 workplaces that had 2,820 and 2,640 employees complete surveys at baseline and 15 months, respectively. Measures: The WSH scale consisted of five items. To assess validity, we examined associations between the WSH scale and employer implementation of evidence-based interventions for health promotion, employee self-rated health, and job satisfaction. Analysis: We performed an exploratory factor analysis to assess the unidimensionality of the WSH scale items, and produced Cronbach’s alpha coefficients to examine scale reliability. We ran regression models using generalized estimating equations to examine validity. Results: The factor analysis indicated one factor, which accounted for 59% of the total variance in the workplace support for health items. The scale had good reliability at baseline (α = 0.82) and 15 months (α = 0.83). Employer evidence-based intervention implementation was positively associated with WSH. WSH was also associated with higher self-rated health and job satisfaction. These associations indicate good concurrent validity. Conclusion: The WSH scale is a reliable and valid measure of perceived workplace support for health. Employers can use the scale to identify gaps in support and create a plan for improvement.

Background RAAPID (Referral, Access, Advice, Placement, Information, and Destination) is a 24-h call center in Alberta, Canada, facilitating urgent telephone consultations between physicians and specialists. We evaluated the extent to which RAAPID calls to Otolaryngology-Head and Neck Surgery (OHNS) reduced visits to the emergency department and specialty clinics. Methods This was a cross-sectional study evaluating all telephone consultations to OHNS from physicians in northern Alberta between 2013 and 2014 (T1) (where consultations by residents occurred) and 2015 to 2017 (T2) (where consultations were done by consultants during office hours and residents during after hours). Outcomes of the calls included medical advice, specialty clinic referrals, and emergency department (ED) referrals. Differences in the reduction of ED visits and costs, overall as well as in T1 and T2, were assessed using multivariate logistic regression. Results Overall, 62.3% (1064/1709) of telephone consultations reduced ED visits consisting of advice being provided (n = 884; 83.1%) and referral to specialty clinics (n = 180; 16.9%). The adjusted odds ratio of calls reducing emergency visits in T2 as compared to T1 was 2.47 (95% CI 1.99 to 3.08). The adjusted odds ratio of reducing ED visits during office hours compared to after-hours 2.54 (95% CI 1.77–3.64). The estimated direct costs avoided from ED visits in T1 and T2 were $42,224.22 and $114,393.86, respectively. Conclusion RAAPID telephone consultations to OHNS were effective in reducing ED visits and healthcare costs. This model should be considered in other areas to improve efficiencies within the health system.

IMPORTANCE: Incorporation of patient perspectives, or patient-reported outcomes, in functional outcome measures has been gaining prominence in the literature on reconstructive surgery. OBJECTIVE: To create and validate an instrument for measuring the main functional areas of concern for patients with head and neck cancer. DESIGN, SETTING, AND PARTICIPANTS: This 4-phase mixed-methods qualitative study was conducted from July 1, 2013, to June 30, 2016, in a quaternary head and neck oncology center in Edmonton, Alberta, Canada. Patients were recruited from 3 Head and Neck Research Network sites: University of Alberta (Edmonton, Canada), Mount Sinai Health Network (New York, New York), and University of Turku Hospital (Turku, Finland). The inclusion criteria included 18 years of age or older, diagnosis of squamous cell carcinoma involving the subsites of the head and neck (ie, oral cavity, oropharynx, hypopharynx, and larynx), and at least 1 year since treatment completion. Those patients who were undergoing additional active treatment or with evidence of disease recurrence were excluded. Data were analyzed from July 1, 2013, to June 30, 2016. MAIN OUTCOMES AND MEASURES: The primary outcome measures were the clinical correlation of the Edmonton-33 instrument scores with swallowing, speech, dry mouth, and chewing assessment outcomes. RESULTS: In total, 10 patients with head and neck cancer (mean age, 59.6 years; 6 men [60%]) were included in phase 1 of the study, 5 patients (mean age, 55.2 years) were included in phase 2, 10 patients were included in phase 3, and 25 patients with head and neck cancer (mean age, 62.6 years; 14 men [56%]) participated in the phase 4 validation. The Edmonton-33 instrument scores correlated strongly with the swallowing scores of the MD Anderson Dysphagia Inventory (r = 0.77; 95% CI, 0.49-1.0), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Head and Neck 35 (EORTC QLQ–H&N35) (r = –0.73; 95% CI, –1.0 to –0.44), and the modified barium swallow test (r = –0.60; 95% CI, –0.94 to –0.25). The instrument scores were also strongly correlated with the Speech Handicap Index scores (r = –0.64; 95% CI, –0.97 to –0.31), word intelligibility scores (r = 0.61; 95% CI, 0.27-0.95), and sentence intelligibility scores (r = 0.55; 95% CI, 0.19-0.91). A moderate to strong correlation was observed between the Edmonton-33 instrument and the EORTC QLQ–H&N35 scores in the dry mouth (r = –0.54; 95% CI, –0.91 to –0.18) and chewing (r = –0.45; 95% CI, –0.84 to –0.06) domains. The factor loading values for the domains of swallowing, speech, dry mouth, and chewing were all greater than 0.3. The mean factor loading values for the items related to swallowing were 0.71 (95% CI, 0.62-0.80) and for the items related to speech were 0.76 (95% CI, 0.72-0.80). The mean factor loading values for the items related to dry mouth were 0.71 (95% CI, 0.59-0.83) and for those related to chewing were 0.77 (95% CI, 0.69-0.85). CONCLUSIONS AND RELEVANCE: The Edmonton-33 appears to be a validated instrument that will allow patients with head and neck cancer to assess and report their own functional outcomes. It could serve as a single comprehensive measure for functional outcomes.

Introduction Evidence-based interventions for tobacco control in the US workplace can reach a large audience. The purpose of our study was to explore the prevalence and determinants of type of tobacco use (ie, cigarettes only, e-cigarettes only, or dual use) among adult employees in the United States and to examine type of use by state. Methods We used data from the 2017 Behavioral Risk Factor Surveillance System to examine the prevalence of cigarette use, e-cigarette use, dual use, and quit attempts. We used multinomial logistic regression to examine the relationships between sociodemographic characteristics and type of tobacco product used, and we estimated adjusted prevalence. Results Approximately 17% of respondents were current smokers, 5% were current e-cigarette users, and 2% were dual users. E-cigarette-only and dual use were generally highest among young (aged 18-24), male, and less-educated respondents and lower for respondents who identified as black, Asian/Native Hawaiian/Pacific Islander, or Hispanic than for white respondents. Cigarette-only and dual use were higher for respondents who did not have health care coverage. Prevalence by state of e-cigarette use only ranged from 1.2% (Vermont) to 3.9% (Arkansas), whereas the prevalence of dual use ranged from 0.6% (District of Columbia) to 4.0% (Oklahoma). Conclusion Prevalence of cigarette, e-cigarette, and dual use varied by sociodemographic characteristics and by state. These findings can support targeting of specific populations when designing and implementing evidence-based interventions for tobacco control in workplace settings.

Purpose: To construct a wellness committee (WC) implementation index and determine whether this index was associated with evidence-based intervention implementation in a workplace health promotion program. Design: Secondary data analysis of the HealthLinks randomized controlled trial. Setting: Small businesses assigned to the HealthLinks plus WC study arm. Sample: Small businesses (20-200 employees, n = 23) from 6 low-wage industries in King County, Washington. Measures: Wellness committee implementation index (0%-100%) and evidence-based intervention implementation (0%-100%). Analysis: We used descriptive and bivariate statistics to describe worksites’ organizational characteristics. For the primary analyses, we used generalized estimating equations with robust standard errors to assess the association between WC implementation index and evidence-based intervention implementation over time. Results: Average WC implementation index scores were 60% at 15 months and 38% at 24 months. Evidence-based intervention scores among worksites with WCs were 27% points higher at 15 months (64% vs 37%, P < .001) and 36% points higher at 24 months (55% vs 18%, P < .001). Higher WC implementation index scores were positively associated with evidence-based intervention implementation scores over time ( P < .001). Conclusion: Wellness committees may play an essential role in supporting evidence-based intervention implementation among small businesses. Furthermore, the degree to which these WCs are engaged and have leadership support, a set plan or goals, and multilevel participation may influence evidence-based intervention implementation and maintenance over time.

Background Recent guidelines for the management of thyroid nodules incorporate mutation testing as an adjunct for surgical decision-making, however current tests are costly with limited accuracy. Droplet digital PCR (ddPCR) is an ultrasensitive method of nucleic acid detection that is particularly useful for identifying gene mutations. This study aimed to assess the analytic and clinical validity of RAS and BRAF ddPCR mutational testing as a diagnostic tool for thyroid fine needle aspirate biopsy (FNAB). Methods Patients with thyroid nodules meeting indication for FNAB were prospectively enrolled from March 2015 to September 2017. In addition to clinical protocol, an additional FNAB was obtained for ddPCR. Optimized ddPCR probes were used to detect mutations including HRASG12 V, HRASQ61K, HRASQ61R, NRASQ61R, NRASQ61K and BRAFV600E. The diagnostic performance of BRAF and RAS mutations was assessed individually or in combination with Bethesda classification against final surgical pathology. Results A total of 208 patients underwent FNAB and mutational testing with the following Bethesda cytologic classification: 26.9% non-diagnostic, 55.2% benign, 5.3% FLUS/AUS, 2.9% FN/SPN, 2.4% SFM and 7.2% malignant. Adequate RNA was obtained from 91.3% (190) FNABs from which mutations were identified in 21.1% of HRAS, 11.5% of NRAS and 7.4% of BRAF. Malignant cytology or BRAFV600E was 100% specific for malignancy. Combining cytology with ddPCR BRAF600E mutations testing increased the sensitivity of Bethesda classification from 41.7 to 75%. Combined BRAFV600E and Bethesda results had a positive predictive value (PPV) of 100% and negative predictive value (NPV) of 89.7% for thyroid malignancy in our cohort. Conclusions DdPCR offers a novel and ultrasensitive method of detecting RAS and BRAF mutations from thyroid FNABs. BRAFV600E mutation testing by ddPCR may serve as a useful adjunct to increase sensitivity and specificity of thyroid FNAB.

The aim of this study was to identify alignments between wellness offerings low socioeconomic status (SES) employees need and those large companies can provide.Focus groups (employees); telephone interviews (large companies). Employees were low-SES, insured through their employers, and employed by large Washington State companies. Focus groups covered perceived barriers to healthy behaviors at work and potential support from companies. Interviews focused on priorities for employee health and challenges reaching low-SES employees.Seventy-seven employees participated in eight focus groups; 12 companies completed interviews. Employees identified facilitators and barriers to healthier work environments; companies expressed care for employees, concerns about employee obesity, and reluctance to discuss SES.Our findings combine low-SES employee and large company perspectives and indicate three ways workplaces could most effectively support low-SES employee health: create healthier workplace food environments; prioritize onsite physical activity facilities; use clearer health communications.

Purpose: The purpose of this study is to evaluate managers’ barriers and facilitators to supporting employee participation in the Washington State Wellness program. Design: Exploratory sequential mixed methods. Setting: Four Washington State agencies located in Olympia and Tumwater, Washington. Participants: State employees in management positions (executive, middle, and line), whose job includes supervision of subordinates and responsibility for the performance and conduct of a subunit or group. Methods: We interviewed 23 managers and then used the results to create a survey that was fielded to all managers at the 4 agencies. The survey response rate was 65% (n = 607/935). Analysis: We used qualitative coding techniques to analyze interview transcripts and descriptive statistics to summarize survey data. We used the Total Worker Health framework to organize our findings and conclusions. Results: Managers support the wellness program, but they also face challenges with accommodating employees’ participation due to workload, scheduling inflexibility, and self-efficacy to discuss wellness with direct reports. About half the managers receive support from the manager above them, and most have not received training on the wellness program. Conclusion: Our findings point to several strategies that can strengthen managers’ role in supporting the wellness program: the provision of training, targeted messages, formal expectations, and encouragement (from the manager above) to support employees’ participation.

With the changing landscape of postgraduate surgical education to competency-based curricula, there emerges a need for alternative forms of training. Video teaching modules have been shown to be effective tools in surgical education, complementing traditional postgraduate curricula. There is a lack of validated modules described in the literature, specifically for teaching thyroidectomy. The primary objective of this study was to develop and validate a high definition video-based teaching module instructing thyroidectomy surgery to Otolaryngology-Head and Neck Surgery trainees.This prospective study included intermediate to senior Otolaryngology-Head and Neck Surgery residents. Each participant first performed a thyroid lobectomy, serving as the initial assessment. After a washout period of at least 3 weeks, each participant was given the teaching module. The 15-minute module was developed using a 3-camera system and detailed a step-by-step approach to the surgery. After exposure to the module, each trainee performed the same procedure. Recordings of both procedures were deidentified and reviewed by a blinded, independent evaluator. Scoring was done using the Observational Clinical Human Reliability Assessment (OCHRA) system.University of Alberta Hospital and Royal Alexandra Hospital, Edmonton, Alberta, Canada.A total of 6 intermediate to senior Otolaryngology-Head and Neck Surgery residents entered and completed the study.The mean error rate was 8.8 errors per procedure before module exposure and 4.5 errors per procedure after exposure, representing a 49% decrease in error occurrence (p0.05). The mean staff takeover event rate was 10.5 takeovers per procedure prior to module exposure and 5.0 takeovers per procedure after exposure, representing a 52% decrease in error occurrence (p0.05).High-definition video teaching modules are a useful complement to traditional surgical training. In a climate where new innovations for teaching thyroid surgery are needed, properly constructed and validated video teaching modules can serve as important tools in supplementing traditional surgical training.