Molecular mechanisms underpinning favourable physiological adaptations to exercise prehabilitation for urological cancer surgery.

BACKGROUND: Surgery for urological cancers is associated with high complication rates and survivors commonly experience fatigue, reduced physical ability and quality of life. High-intensity interval training (HIIT) as surgical prehabilitation has been proven effective for improving the cardiorespiratory fitness (CRF) of urological cancer patients, however the mechanistic basis of this favourable adaptation is undefined. Thus, we aimed to assess the mechanisms of physiological responses to HIIT as surgical prehabilitation for urological cancer. METHODS: Nineteen male patients scheduled for major urological surgery were randomised to complete 4-weeks HIIT prehabilitation (71.6 ± 0.75 years, BMI: 27.7 ± 0.9 kg·m2) or a no-intervention control (71.8 ± 1.1 years, BMI: 26.9 ± 1.3 kg·m2). Before and after the intervention period, patients underwent m. vastus lateralis biopsies to quantify the impact of HIIT on mitochondrial oxidative phosphorylation (OXPHOS) capacity, cumulative myofibrillar muscle protein synthesis (MPS) and anabolic, catabolic and insulin-related signalling. RESULTS: OXPHOS capacity increased with HIIT, with increased expression of electron transport chain protein complexes (C)-II (p = 0.010) and III (p = 0.045); and a significant correlation between changes in C-I (r = 0.80, p = 0.003), C-IV (r = 0.75, p = 0.008) and C-V (r = 0.61, p = 0.046) and changes in CRF. Neither MPS (1.81 ± 0.12 to 2.04 ± 0.14%·day-1, p = 0.39) nor anabolic or catabolic proteins were upregulated by HIIT (p > 0.05). There was, however, an increase in phosphorylation of AS160Thr642 (p = 0.046) post-HIIT. CONCLUSIONS: A HIIT surgical prehabilitation regime, which improved the CRF of urological cancer patients, enhanced capacity for skeletal muscle OXPHOS; offering potential mechanistic explanation for this favourable adaptation. HIIT did not stimulate MPS, synonymous with the observed lack of hypertrophy. Larger trials pairing patient-centred and clinical endpoints with mechanistic investigations are required to determine the broader impacts of HIIT prehabilitation in this cohort, and to inform on future optimisation (i.e., to increase muscle mass).

In-Person Clinic Visits After Laparoscopic Cholecystectomy: Lessons Learned From COVID-19 Pandemic.

INTRODUCTION: The utility of routine in-person clinic appointments after laparoscopic cholecystectomy (LC) is uncertain, especially after the increase of telehealth visits during the COVID-19 pandemic. The purpose of this study was to evaluate the utility of routine in-person follow-up for patients undergoing LC prior to changes implemented during the pandemic and to determine whether a return to routine in-person follow-up is warranted. METHODS: We retrospectively reviewed follow-up encounters for all patients undergoing LC from April 2018 to February 2020. All patients were routinely scheduled for in-person postoperative clinic follow-up 2-4 wk after discharge. Follow-up was considered nonroutine if new studies or medications were ordered, the patient was referred to the emergency department or readmitted, or malignancy was identified on pathology review. RESULTS: Of 661 patients undergoing LC, 449 (68%) attended their scheduled in-person postoperative appointment and 212 (32%) did not. The postoperative appointment was nonroutine for 39 patients (9% of clinic attenders). Readmission occurred in 42 patients, with no differences between clinic attenders and nonattenders (P = 0.12). Furthermore, attending a postoperative clinic visit did not affect odds of readmission (odds ratio: 0.705, 95% confidence interval: 0.368, 1.351; P = 0.29). Readmission occurred on median day 9 after discharge in both groups. CONCLUSIONS: The incidence of nonroutine follow-up after LC is low, and attendance at follow-up clinic was not associated with reduced readmissions. A return to routinely scheduling in-person follow-up 2-4 wk after discharge may not be warranted. Telehealth visits within 1 wk of discharge after LC should be considered.

Integrating principles and tools of decision science into value-driven watershed planning for compensatory mitigation.

Several environmental policies strive to restore impaired ecosystems and could benefit from a consistent and transparent process-codeveloped with key stakeholders-to prioritize impaired ecosystems for restoration activities. The Clean Water Act, for example, establishes reallocation mechanisms to transfer ecosystem services from sites of disturbance to compensation sites to offset aquatic resource functions that are unavoidably lost through land development. However, planning for the prioritization of compensatory mitigation areas is often hampered by decision-making processes that fall into a myopic decision frame because they are not coproduced with stakeholders. In this study, we partnered with domain experts from the North Carolina Division of Mitigation Services to codevelop a real-world decision framework to prioritize catchments by potential for the development of mitigation projects following principles of a structured decision-making process and knowledge coproduction. Following an iterative decision analysis cycle, domain experts revised foundational components of the decision framework and progressively added complexity and realism as they gained additional insights or more information became available. Through the course of facilitated in-person and remote interactions, the codevelopment of a decision framework produced three main "breakthroughs" from the perspective of the stakeholder group: (a) recognition of the problem as a multiobjective decision driven by several values in addition to biogeophysical goals (e.g., functional uplift, restoring or enhancing lost functionality of ecosystems); (b) that the decision comprises a linked and sequential planning-to-implementation process; and (c) future risk associated with land-use and climate change must be considered. We also present an interactive tool for "on-the-fly" assessment of alternatives and tradeoff analysis, allowing domain experts to quickly test, react to, and revise prioritization strategies. The decision framework described in this study is not limited to the prioritization of compensatory mitigation activities across North Carolina but rather serves as a framework to prioritize a wide range of restoration, conservation, and resource allocation activities in similar environmental contexts across the nation.

Understanding the effect of direct-acting antiviral therapy on weight in patients with chronic hepatitis C.

BACKGROUND: Direct-acting antivirals (DAAs) have revolutionized treatment for HCV. Compared to interferon-based therapies, DAAs achieve higher rates of sustained virologic response, with more tolerable side effects. Nonetheless, interferon-based therapies have the potential to cause weight loss, and literature documenting the impact of DAAs on weight is limited. Appetite suppression may occur with chronic HCV. It is plausible that DAAs may indirectly cause weight gain given their ability to cause rapid virologic suppression, leading to improved hepatic function. METHODS: A retrospective chart review identified 220 patients who initiated DAA therapy between 1 February 2019, and 29 February 2020. Patients 18 years and older who completed therapy with a DAA were included in the study if they had a documented initial weight (weight on the day therapy was initiated) and final weight (weight 12 weeks after therapy completion). Change in weight was assessed as the primary outcome. Comorbidities with the potential to impact weight were assessed as confounders. RESULTS: Multiple variables were analyzed and baseline BMI was the only factor that influenced a change in weight (P = 0.016). Patients with a higher BMI at baseline experienced statistically significant weight gain. Weight was increased by 0.14 kg per unit of BMI (95% CI: 0.026, 0.25). Patient demographics relating to age and gender, progression of cirrhosis and concurrent comorbidities had no statistically significant impact on change in weight. CONCLUSION: Weight changes after treatment with a DAA may be related to the individual's weight prior to treatment.

Social Media Perceptions and Internet Verification Skills Associated With Human Papillomavirus Vaccine Decision-Making Among Parents of Children and Adolescents: Cross-sectional Survey.

BACKGROUND: Human Papillomavirus (HPV) vaccination is recommended for children aged 11-12 years in the United States. One factor that may contribute to low national HPV vaccine uptake is parental exposure to misinformation on social media. OBJECTIVE: This study aimed to examine the association between parents' perceptions of the HPV vaccine information on social media and internet verification strategies used with the HPV vaccine decision-making stage for their child. METHODS: Parents of children and adolescents aged 9-17 years were recruited for a cross-sectional survey in North Texas (n=1192) and classified into 3 groups: children and adolescents who (1) were vaccinated, (2) unvaccinated and did not want the vaccine, and (3) unvaccinated and wanted the vaccine. Multinomial logistic regression models were estimated to identify factors associated with the HPV vaccine decision-making stage with children and adolescents who were vaccinated as the referent group. RESULTS: Of the 1192 respondents, 44.7% (n=533) had an HPV-vaccinated child, 38.8% (n=463) had an unvaccinated child and did not want the vaccine, and 16.4% (n=196) had an unvaccinated child and wanted the vaccine. Respondents were less likely to be "undecided/not wanting the vaccine" if they agreed that HPV information on social media is credible (adjusted odds ratio [aOR] 0.40, 95% CI 0.26-0.60; P=.001), disagreed that social media makes them question the HPV vaccine (aOR 0.22, 95% CI 0.15-0.33; P<.001), or had a higher internet verification score (aOR 0.74, 95% CI 0.62-0.88; P<.001). CONCLUSIONS: Interventions that promote web-based health literacy skills are needed so parents can protect their families from misinformation and make informed health care decisions.

Characteristics and outcomes of young patients with laryngeal cancer: National hospital-based retrospective cohort analysis.

BACKGROUND: The relative incidence of laryngeal cancer is rising in young patients, yet their characteristics, risk factors, and outcomes relative to older patients are poorly understood. METHODS: Retrospective cohort analysis of the National Cancer Database from 2006 to 2015. RESULTS: Among 25 029 total patients, 923 (3.7%) were young (<45 years old) and 3266 underwent tumor HPV testing. Compared to older patients, a greater proportion of young patients were female (30.3%, 23.3%; p < 0.001) and seen with high-risk HPV-positive tumors (29.9%, 12.4%; p < 0.001). In subset analyses of young patients, females with higher income (≥$38 000) exhibited a decreased risk of overall mortality compared to all other sex-income subcategories (adjusted hazard ratio [aHR]: 0.43, 95% confidence interval [CI]: 0.25-0.72). In subset analyses of patients of all ages with known tumor HPV status, patients with high-risk HPV-positive tumors exhibited a reduced risk of all-cause mortality (aHR: 0.74, 95%CI: 0.60-0.92, p = 0.007). CONCLUSION: The interdependent associations between age, sex, tumor HPV status, and income on laryngeal cancer outcomes warrant further investigation.

Provider Perception of Time During Trauma Resuscitation: A Prospective Quantitative Trauma Video Review Analysis.

INTRODUCTION: Delays in transition to the next phase of care result in increased mortality. Prehospital literature suggests emergency medical service technicians underestimate transport times by as much as 20%. What remains unknown is clinician perception of time during the trauma resuscitation. We sought to determine if clinicians have an altered perception of time. We hypothesized that clinicians underestimate time, resulting in delay of care. METHODS: Clinicians at a large level 1 trauma center completed a post-trauma activation survey on the perceived elapsed time to complete three specific resuscitation endpoints. The primary study endpoint was the time to the next phase of care, defined as leaving the trauma bay to go to the operating room, interventional radiology, computerized tomography or time of death. The data from the surveys were linked and compared with recorded videos of the resuscitations. The difference in perceived versus actual time, along with confounding variables, was used to assess the impact of perception of time on the time to the next phase of care using a stepwise multivariate linear model. RESULTS: There were 284 complete surveys and videos, culminating in 543 time points. The median perceived versus actual time (minutes [interquartile range]) to the next phase of care was 20 [10-25] versus 26 [19-40] (P < 0.001). Overall, clinicians underestimated time by 28%, such that if the resuscitation lasted 20 min, the clinician's perception was that 14.4 min elapsed. Differences in the perceived versus actual time in the procedure group impacted time to the next phase of care (P = 0.01). CONCLUSIONS: Clinicians have significant gaps in the perception of time during trauma resuscitations. This misperception occurs during procedures and correlates with an increase in the length of time to the next phase of care.

Proton Resonance Frequency Shift Thermometry: A Review of Modern Clinical Practices.

Magnetic resonance imaging (MRI) has become a popular modality in guiding minimally invasive thermal therapies, due to its advanced, nonionizing, imaging capabilities and its ability to record changes in temperature. A variety of MR thermometry techniques have been developed over the years, and proton resonance frequency (PRF) shift thermometry is the current clinical gold standard to treat a variety of cancers. It is used extensively to guide hyperthermic thermal ablation techniques such as high-intensity focused ultrasound (HIFU) and laser-induced thermal therapy (LITT). Essential attributes of PRF shift thermometry include excellent linearity with temperature, good sensitivity, and independence from tissue type. This noninvasive temperature mapping method gives accurate quantitative measures of the temperature evolution inside biological tissues. In this review, the current status and new developments in the fields of MR-guided HIFU and LITT are presented with an emphasis on breast, prostate, bone, uterine, and brain treatments. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 3.

Depression and Anxiety Are Common Among Patients With Cirrhosis.

BACKGROUND & AIMS: Depression and anxiety can have negative effects on patients and are important to treat. There have been few studies of their prevalence among patients with cirrhosis. We aimed to characterize the prevalence and risk factors for depression and anxiety in a large multi-center cohort of patients with cirrhosis. METHODS: We conducted a telephone-based survey of patients with cirrhosis at 3 health systems in the United States (a tertiary-care referral center, a safety net system, and a Veterans hospital) from April through December 2018. Of 2871 patients approached, 1021 (35.6%) completed the survey. Depression and anxiety were assessed using the PHQ-9 (range 0-25) and STAI (range 20-80) instruments, with clinically significant values defined as PHQ-9 ≥15 and STAI ≥40. We performed multivariate logistic regression analysis to identify factors associated with significant depression and anxiety. RESULTS: The median PHQ-9 score was 7 (25th percentile-75th percentile, 3-12) and the median STAI score was 33 (25th percentile-75th percentile, 23-47); 15.6% of patients had moderately severe to severe depression and 42.6% of patients had high anxiety. In multivariable analyses, self-reported poor health (odds ratio [OR], 4.08; 95% CI, 1.79-9.28), being widowed (OR, 2.08; 95% CI, 1.07-4.05), fear of hepatocellular carcinoma (OR, 1.89; 95% CI, 1.04-3.42), higher household income (OR, 0.30; 95% CI, 0.10-0.95), and Hispanic ethnicity (OR, 0.57; 95% CI, 0.33-0.97) were associated with moderately severe to severe depression. Male sex (OR, 0.71; 95% CI, 0.51-0.98), self-reported poor health (OR, 2.73; 95% CI, 1.73-4.32), and fear of hepatocellular carcinoma (OR, 2.24; 95% CI, 1.33-3.78) were associated with high anxiety. CONCLUSIONS: Nearly 1 in 6 patients with cirrhosis have moderately severe to severe depression and nearly half have moderate-severe anxiety. Patients with cirrhosis should be evaluated for both of these disorders.

Extracapsular extension, pathologic node status, and adjuvant treatment in primary surgery patients with human papillomavirus-mediated oropharyngeal cancer: National hospital-based retrospective cohort analysis.

BACKGROUND: The significance of extracapsular extension (ECE) and adjuvant treatment paradigm in patients with surgically managed human papillomavirus-positive (HPV+) oropharyngeal cancer (OPC) is debated. METHODS: National, hospital-based, retrospective cohort study of 2663 patients pN+ HPV+ OPC who underwent primary surgery. RESULTS: Patients with ECE had a 1.74-times risk of death (95% confidence interval [CI]: 1.26-2.40, p = 0.001) compared to patients without ECE. Among patients with pN1, ECE-positive disease, risk of overall mortality was similar across treatment paradigms (surgery alone: ref; adjuvant radiation therapy [RT]: aHR: 0.81; 95% CI: 0.36-1.85; p = 0.62; adjuvant CRT: aHR: 0.66; 95% CI: 0.34-1.32; p = 0.24). Patients with pN2 ECE-positive disease treated with adjuvant RT alone exhibited similar risk of all-cause mortality (hazard ratio: 1.04, 95% CI: 0.24-4.47, p = 0.96) compared to adjuvant chemoradiation (CRT). In patients with advanced, ECE-positive disease (e.g., pT3-T4pN2), adjuvant CRT did not reduce the risk of overall mortality relative to adjuvant RT. CONCLUSION: Although pathologic ECE negatively predicts for survival in patients with HPV+ OPC, our analyses support expansion of postoperative de-intensification clinical trial eligibility criteria in patients with ECE-positive disease.

The physiological impact of high-intensity interval training in octogenarians with comorbidities.

BACKGROUND: Declines in cardiorespiratory fitness (CRF) and fat-free mass (FFM) with age are linked to mortality, morbidity and poor quality of life. High-intensity interval training (HIIT) has been shown to improve CRF and FFM in many groups, but its efficacy in the very old, in whom comorbidities are present is undefined. We aimed to assess the efficacy of and physiological/metabolic responses to HIIT, in a cohort of octogenarians with comorbidities (e.g. hypertension and osteoarthritis). METHODS: Twenty-eight volunteers (18 men, 10 women, 81.2 ± 0.6 years, 27.1 ± 0.6 kg·m-2 ) with American Society of Anaesthesiology (ASA) Grade 2-3 status each completed 4 weeks (12 sessions) HIIT after a control period of equal duration. Before and after each 4 week period, subjects underwent body composition assessments and cardiopulmonary exercise testing. Quadriceps muscle biopsies (m. vastus lateralis) were taken to quantify anabolic signalling, mitochondrial oxidative phosphorylation, and cumulative muscle protein synthesis (MPS) over 4-weeks. RESULTS: In comorbid octogenarians, HIIT elicited improvements in CRF (anaerobic threshold: +1.2 ± 0.4 ml·kg-1 ·min-1 , P = 0.001). HIIT also augmented total FFM (47.2 ± 1.4 to 47.6 ± 1.3 kg, P = 0.04), while decreasing total fat mass (24.8 ± 1.3 to 24 ± 1.2 kg, P = 0.0002) and body fat percentage (33.1 ± 1.5 to 32.1 ± 1.4%, P = 0.0008). Mechanistically, mitochondrial oxidative phosphorylation capacity increased after HIIT (i.e. citrate synthase activity: 52.4 ± 4 to 67.9 ± 5.1 nmol·min-1 ·mg-1 , P = 0.005; membrane protein complexes (C): C-II, 1.4-fold increase, P = 0.002; C-III, 1.2-fold increase, P = 0.03), as did rates of MPS (1.3 ± 0.1 to 1.5 ± 0.1%·day-1 , P = 0.03). The increase in MPS was supported by up-regulated phosphorylation of anabolic signalling proteins (e.g. AKT, p70S6K, and 4E-BP1; all P < 0.05). There were no changes in any of these parameters during the control period. No adverse events were reported throughout the study. CONCLUSIONS: The HIIT enhances skeletal muscle mass and CRF in octogenarians with disease, with up-regulation of MPS and mitochondrial capacity likely underlying these improvements. HIIT can be safely delivered to octogenarians with disease and is an effective, time-efficient intervention to improve muscle mass and physical function in a short time frame.

Blood Conservation and Hemostasis in Cardiac Surgery: A Survey of Practice Variation and Adoption of Evidence-Based Guidelines.

BACKGROUND: Blood conservation and hemostasis are integral parts of reducing avoidable blood transfusions and the associated morbidity and mortality. Despite the publication of blood conservation guidelines for cardiac surgery, evidence suggests persistent variability in practice patterns. Members of the Society of Cardiovascular Anesthesiologists (SCA) created a survey to audit conformance to existing guidelines and use the results to help narrow the evidence-to-practice gap. METHODS: Members of the SCA and its Continuous Practice Improvement (CPI)- Blood Conservation Work Group developed a 48-item Blood Conservation and Hemostasis in Cardiac Surgery (BCHCS) survey. The questionnaire included the components of the Anesthesia Quality Institute's (AQI) composite measure AQI49. The survey was distributed to the entire SCA membership by e-mail via the Research Electronic Data Capture (REDCap) Consortium between the fall of 2017 and early 2018. RESULTS: Of 3152 SCA members, 536 returned surveys for a response rate of 17%. Most responders worked at academic institutions. The median transfusion trigger after cardiopulmonary bypass was hemoglobin (Hgb) 7.0 to 8.0 g/dL. There are 4 components to AQI49, and the composite conformance to all of them was low due to 1 specific component: the use of transfusion algorithms supplemented with point-of-care (POC) testing. There was good conformance to the other 3 components of AQI49: use of antifibrinolytics, minimization of hemodilution and use of red cell salvage. Overall, practices with a multidisciplinary patient blood management (PBM) team were the most successful in meeting all 4 AQI49 criteria. CONCLUSIONS: The survey demonstrated widespread adoption of several best practices, including the tolerance of lower hemoglobin transfusion triggers, use of antifibrinolytics, minimization of hemodilution, and use of red cell salvage. The survey also confirms that gaps remain in preoperative anemia management and the use of transfusion algorithms supplemented with POC hemostasis testing. Serial use of this survey can be used to identify barriers to implementation and audit the effectiveness of interventions described in this article. This instrument could also help harmonize local, regional, and national efforts and become an essential component of an implementation strategy for PBM in cardiac surgery.

Redefining High-Volume Gastric Cancer Centers: The Impact of Operative Volume on Surgical Outcomes.

BACKGROUND: Performance of technically complex surgery at high-volume (HV) centers is associated with improved outcomes. OBJECTIVE: The aim of this study was to assess whether hospital gastrectomy volume is associated with surgical outcomes, and what threshold of case volume meaningfully impacts surgical outcomes. METHODS: We conducted a retrospective review of adult NCDB patients with gastric adenocarcinoma undergoing gastrectomy between 2004 and 2015. A multivariable Cox proportional hazards model with restricted cubic splines was used to examine the association of annual hospital gastrectomy volume and overall survival. Bootstrap simulation was used to estimate the cut-point corresponding to maximum change in log hazard ratio. Hospitals were divided into HV (≥ 17 cases/year) and low-volume (LV; < 17 cases/year) groups. We examined the relationship between volume groups and adequate nodal examination, R0 resection, unplanned readmission, and 30- and 90-day mortality. RESULTS: Our cohort consisted of 29,559 patients (7.8% treated at an HV center). Treatment at an HV center was associated with an increased likelihood of adequate nodal examination [odds ratio (OR) 2.12, 95% confidence interval (CI) 1.94-2.32] and R0 resection among patients with cardia tumors (OR 1.42, 95% CI 1.07-1.88). Patients treated at HV centers had decreased 30- and 90-day postoperative mortality, which was more pronounced in those undergoing total gastrectomy. CONCLUSIONS: Treatment at an HV gastrectomy center is associated with improved surgical outcomes. Our study identified 17 cases/year as a clinically meaningful distinction between HV and LV centers. This definition of an HV center should be considered when evaluating regionalization of gastric cancer care to improve patient outcomes.

Inaccurate Clinical Stage Is Common for Gastric Adenocarcinoma and Is Associated with Undertreatment and Worse Outcomes.

BACKGROUND: Accurate clinical staging (CS) of gastric cancer is critical for appropriate treatment selection and prognostication, but CS remains highly imprecise. Our study evaluates factors associated with inaccurate CS, the impact of inaccurate CS on outcomes, and utilization of adjuvant therapy in patients who are understaged. METHODS: We conducted a retrospective review of NCDB patients diagnosed with clinical early stage gastric adenocarcinoma (cT1-2N0M0) between 2004 and 2016. Patients not undergoing upfront gastrectomy or with missing pathologic staging were excluded. Patients were classified as accurately staged, inaccurately staged with receipt of adjuvant therapy (IS+), and inaccurately staged with no receipt of adjuvant therapy (IS-). Logistic regression was utilized to assess the impact of factors on CS accuracy and receipt of adjuvant therapies. Kaplan-Meier and Cox proportional hazard methods were used for survival analysis. RESULTS: Approximately 40% of patients were inaccurately staged (IS). cT2, moderately/poorly differentiated, and site-overlapping tumors were associated with increased likelihood of being IS. Treatment at an academic facility was associated with decreased likelihood of understaging. Only 54% of patients who were IS received adjuvant therapy. CONCLUSION: Accurate CS of gastric cancer remains inadequate. Understaging is associated with detrimental effects on receiving guideline-concordant care and, possibly, patient outcomes. Targeted interventions reducing the proportion of understaged patients and ensuring receipt of appropriate therapy is needed to optimize outcomes. Patients with high-risk disease that are frequently understaged may benefit from selective neoadjuvant therapy. Centralization of gastric cancer care may also be a key strategy in improving receipt of guideline-concordant therapies.

Changes in pediatric trauma during COVID-19 stay-at-home epoch at a tertiary pediatric hospital.

BACKGROUND: Trauma is the leading cause of morbidity and mortality in the pediatric population. However, during the societal disruptions secondary to the coronavirus (COVID-19) stay-at-home regulations, there have been reported changes to the pattern and severity of pediatric trauma. We review our two-institution experience. METHODS: Pediatric trauma emergency department (ED) encounters from the National Trauma Registry for a large, tertiary, metropolitan level 1 pediatric trauma center and pediatric burn admission at the regional burn center were extracted for children less than 19 years from March 15th thru May 15th during the years 2015-2020. The primary outcome was the difference in encounters during the COVID-19 (2020) epoch versus the pre-COVID-19 epoch (2015-2019). RESULTS: There were 392 pediatric trauma encounters during the COVID-19 epoch as compared to 451, 475, 520, 460, 432 (mean 467.6) during the pre-COVID-19 epoch. Overall trauma admissions and ED trauma encounters were significantly lower (p < 0.001) during COVID-19. Burn injury admissions (p < 0.001) and penetrating trauma encounters (p = 0.002) increased during the COVID-19 epoch while blunt trauma encounters decreased (p < 0.001). Trauma occurred among more white (p = 0.01) and privately insured (p < 0.001) children, but no difference in suspected abuse, injury severity, mortality, age, or gender were detected. Sub-analysis showed significant decreases in motor vehicle crashes (p < 0.001), pedestrians struck by automobile (p < 0.001), all-terrain vehicle (ATV)/motorcross/bicycle/skateboard involved injuries (p = 0.02), falls (p < 0.001), and sports related injuries (p < 0.001). Fewer injuries occurring in the playground or home play equipment such as trampolines neared significance (p = 0.05). Interpersonal violence (assault, NAT, self-harm) was lower during the COVID-19 era (p = 0.04). For burn admissions, there was a significant increase in flame burns (p < 0.001). CONCLUSIONS: Stay-at-home regulations alter societal patterns, leading to decreased overall and blunt traumas. However, the proportion of penetrating and burn injuries increased. Owing to increased stressors and time spent at home, healthcare professionals should keep a high suspicion for abuse and neglect.

Randomized Clinical Trial of Inreach With or Without Mailed Outreach to Promote Hepatitis C Screening in a Difficult-to-Reach Patient Population.

INTRODUCTION: Hepatitis C virus (HCV) treatment can significantly reduce the risk of liver-related mortality; however, many patients remain unaware of their infection in clinical practice. The aim of this study is to compare the effectiveness of inreach, with and without mailed outreach, to increase HCV screening and follow-up in a large, difficult-to-reach patient population. METHODS: We conducted a pragmatic randomized clinical trial from August 2018 to May 2019 in a large safety-net health system. Patients born between 1945 and 1965 were randomly assigned (1:1) to inreach with an electronic health record reminder to providers (n = 6,195) or inreach plus mailed HCV screening outreach (n = 6,191) to complete HCV antibody screening. Outreach also included processes to promote HCV RNA testing among those with a positive HCV antibody and linkage to care among those with positive HCV RNA. The primary outcome was completion of HCV antibody testing within 3 months of randomization (ClinicalTrials.gov NCT03706742). RESULTS: We included 12,386 eligible patients (median age 60 years; 46.5% Hispanic, 33.0% Black, and 16.0% White). In intent-to-treat analyses, HCV screening completion was significantly higher among inreach-plus-outreach patients than inreach-alone patients at 3 months (14.6% vs 7.4%, P < 0.001) and 6 months (17.4% vs 9.8%, P < 0.001) after randomization. Among those who completed HCV screening within 6 months, a higher proportion of inreach-plus-outreach patients with positive antibody results completed RNA testing within 3 months than inreach-alone patients (81.1% vs 57.1%, respectively, P = 0.02); however, linkage to care within 3 months of HCV infection confirmation did not significantly differ between the 2 groups (48.1% vs 75.0%, respectively, P = 0.24). DISCUSSION: Among difficult-to-reach patients, a combination of inreach and mailed outreach significantly increased HCV screening compared with inreach alone. However, HCV screening completion in both arms remained low, highlighting a need for more intensive interventions.

Blood-based biomarkers of human papillomavirus-associated cancers: A systematic review and meta-analysis.

BACKGROUND: Despite the significant societal burden of human papillomavirus (HPV)-associated cancers, clinical screening interventions for HPV-associated noncervical cancers are not available. Blood-based biomarkers may help close this gap in care. METHODS: Five databases were searched, 5687 articles were identified, and 3631 unique candidate titles and abstracts were independently reviewed by 2 authors; 702 articles underwent a full-text review. Eligibility criteria included the assessment of a blood-based biomarker within a cohort or case-control study. RESULTS: One hundred thirty-seven studies were included. Among all biomarkers assessed, HPV-16 E seropositivity and circulating HPV DNA were most significantly correlated with HPV-associated cancers in comparison with cancer-free controls. In most scenarios, HPV-16 E6 seropositivity varied nonsignificantly according to tumor type, specimen collection timing, and anatomic site (crude odds ratio [cOR] for p16+ or HPV+ oropharyngeal cancer [OPC], 133.10; 95% confidence interval [CI], 59.40-298.21; cOR for HPV-unspecified OPC, 25.41; 95% CI, 8.71-74.06; cOR for prediagnostic HPV-unspecified OPC, 59.00; 95% CI, 15.39-226.25; cOR for HPV-unspecified cervical cancer, 12.05; 95% CI, 3.23-44.97; cOR for HPV-unspecified anal cancer, 73.60; 95% CI, 19.68-275.33; cOR for HPV-unspecified penile cancer, 16.25; 95% CI, 2.83-93.48). Circulating HPV-16 DNA was a valid biomarker for cervical cancer (cOR, 15.72; 95% CI, 3.41-72.57). In 3 cervical cancer case-control studies, cases exhibited unique microRNA expression profiles in comparison with controls. Other assessed biomarker candidates were not valid. CONCLUSIONS: HPV-16 E6 antibodies and circulating HPV-16 DNA are the most robustly analyzed and most promising blood-based biomarkers for HPV-associated cancers to date. Comparative validity analyses are warranted. Variations in tumor type-specific, high-risk HPV DNA prevalence according to anatomic site and world region highlight the need for biomarkers targeting more high-risk HPV types. Further investigation of blood-based microRNA expression profiling appears indicated.

Provider perspectives on communication and dismissal policies with HPV vaccine hesitant parents.

Parental vaccine hesitancy is a growing concern. Less is known about provider or practice characteristics that encounter HPV-specific vaccine-hesitant parents, the providers' confidence in responding to HPV vaccine concerns, and the attitudes and use of vaccine dismissal policies (i.e., removing patients from the practice). North Texas providers completed an online survey. Dependent variables assessed: (1) percentage of HPV vaccine-hesitant parents encountered in practice defined as substantive, or high (≥11%, or among more than one out of ten adolescent patient encounters) versus low (≤10%) levels; (2) confidence in responding to 11 HPV vaccine concerns; (3) attitudes and use of vaccine dismissal policies. Chi-square and Fisher's exact tests were conducted. Among 156 providers, 29% reported high HPV vaccine hesitancy (≥11% of patient population). Overall, providers reported being "very confident" in addressing vaccine concerns (mean: 3.37 out of 4, SD: 0.57). Mean confidence scores were significantly higher for white (vs. non-white) providers and for pediatricians (vs. family practitioners). Providers were least confident in responding to parents' religious/personal beliefs (69%). Some providers (25%) agreed with policies that dismissed vaccine-hesitant parents after repeated counseling attempts. More providers used dismissal policies for childhood (19%) than adolescent (10%) immunizations. Provider communication training should include parental religious/personal beliefs to effectively address HPV vaccine hesitancy. Other regions should examine their HPV-specific vaccine hesitancy levels to understand how the use of dismissal policies might vary between adolescent and childhood immunizations.

Patient-Reported Barriers Are Associated With Receipt of Hepatocellular Carcinoma Surveillance in a Multicenter Cohort of Patients With Cirrhosis.

BACKGROUND: More than 20% of patients with cirrhosis do not receive semi-annual hepatocellular carcinoma (HCC) surveillance as recommended. Few studies have evaluated the effects of patient-level factors on surveillance receipt. METHODS: We administered a telephone survey to a large cohort of patients with cirrhosis from 3 health systems (a tertiary care referral center, a safety-net health system, and Veterans Affairs) to characterize patient knowledge, attitudes, and perceived barriers of HCC surveillance. Multinomial logistic regression was performed to identify factors associated with HCC surveillance receipt (semi-annual and annual vs none) during the 12-month period preceding survey administration. RESULTS: Of 2871 patients approached, 1020 (35.5%) completed the survey. Patients had high levels of concern about developing HCC and high levels of knowledge about HCC. However, patients had knowledge deficits, including believing surveillance was unnecessary when physical examination and laboratory results were normal. Nearly half of patients reported barriers to surveillance, including costs (28.9%), difficulty scheduling (24.1%), and transportation (17.8%). In the year before the survey, 745 patients (73.1%) received 1 or more surveillance examination; 281 received on-schedule, semi-annual surveillance and 464 received annual surveillance. Semi-annual HCC surveillance (vs none) was significantly associated with receipt of hepatology subspecialty care (odds ratio, 30.1; 95% CI, 17.5-51.8) and inversely associated with patient-reported barriers (odds ratio, 0.62; 95% CI, 0.41-0.94). Patterns of associations comparing annual vs no surveillance were similar although the magnitude of effects were reduced. CONCLUSIONS: Patient-reported barriers such as knowledge deficits, costs, difficulty scheduling, and transportation are significantly associated with less frequent receipt of HCC surveillance, indicating a need for patient-centered interventions, such as patient navigation.

The impact of implementation of a hysterectomy enhanced recovery pathway on anesthetic medication costs.

Aim: To evaluate the effect of implementation of a hysterectomy Enhanced Recovery After Surgery (ERAS) protocol on perioperative anesthetic medication costs. Patients & methods: Historical cohort study of 84 adult patients who underwent a hysterectomy. Forty-two patients who underwent surgery before protocol implementation comprised the pre-ERAS group. Forty-two patients who underwent surgery after protocol implementation comprised the post-ERAS group. Data on anesthetic medication costs and outcomes were analyzed. Results: Compared with the pre-ERAS group, the post-ERAS group's total medication cost was significantly lower (median: 325.20 USD; interquartile range [IQR]: 256.12-430.65 USD vs median: 273.10 USD; IQR: 220.63-370.59 USD, median difference: -40.76, 95% CI: -130.39, 16.99, p = 0.047). Length of stay was significantly longer in pre-ERAS when compared with post-ERAS groups (median: 5.0 days; IQR: 4.0-7.0 days vs median: 3.0 days; IQR: 3.0-4.0 days, median difference: -2.0 days, 95% CI: -2.5581, -1.4419, p < 0.0001). Conclusion: ERAS protocols may reduce perioperative medication costs.