Biological biomarkers of oral cancer.

The oral squamous cell carcinoma (OSCC) 5 year survival rate of 41% has marginally improved in the last few years, with less than a 1% improvement per year from 2005 to 2017, with higher survival rates when detected at early stages. Based on histopathological grading of oral dysplasia, it is estimated that severe dysplasia has a malignant transformation rate of 7%-50%. Despite these numbers, oral dysplasia grading does not reliably predict its clinical behavior. Thus, more accurate markers predicting oral dysplasia progression to cancer would enable better targeting of these lesions for closer follow-up, especially in the early stages of the disease. In this context, molecular biomarkers derived from genetics, proteins, and metabolites play key roles in clinical oncology. These molecular signatures can help predict the likelihood of OSCC development and/or progression and have the potential to detect the disease at an early stage and, support treatment decision-making and predict treatment responsiveness. Also, identifying reliable biomarkers for OSCC detection that can be obtained non-invasively would enhance management of OSCC. This review will discuss biomarkers for OSCC that have emerged from different biological areas, including genomics, transcriptomics, proteomics, metabolomics, immunomics, and microbiomics.

Internal Medicine Resident Barriers to Advance Care Planning in the Primary Care Continuity Clinic.

Background: While primary care providers regularly engage in Advance Care Planning (ACP) conversations, it is not well known what challenges resident physicians face to achieving this core competency. Objectives: We aimed to assess resident perceptions of barriers and potential interventions to outpatient ACP. Methods: We distributed an electronic survey to Internal Medicine and Medicine-Psychiatry residents at our institution in 2022. Questions addressed outpatient ACP barriers and potential interventions in several domains: structural issues, personal knowledge, and communication skills. We reported results using descriptive statistics and Wilcoxon rank-sum tests, comparing responses by residency year (interns vs upperyears). Likert-scale responses were dichotomized to a "not at all or slightly" vs "moderate or extreme" barrier or helpful intervention. Results: Of 149 residents, 71 completed the survey (48%). Highest scoring barriers were structural, including 1) lack of clinic time (99%), 2) need to prioritize other medical problems (94%), and 3) lack of patient continuity (62%). Highest scoring interventions included the ability to schedule dedicated ACP visits with themselves (96%) or another clinician (82%). Interns were statistically significantly less confident in their ability to conduct ACP, and more likely to report lack of knowledge (i.e., not understanding ACP, patient prognosis, or how to complete paperwork, P < .05). Conclusions: Residents report significant structural barriers to outpatient ACP, including limitations in time, continuity, and competing medical priorities, that may warrant greater program attention to interventions such as clinic schedules and work-flow. Additional trainings may be most beneficial if targeted to the beginning of intern year.

Two-year outcomes following the HIDOC program: expanding outpatient care delivery to meet the needs of medically complex, high-utilizing patients with a broader interprofessional care team.

This article describes the Highly Individualized Dedicated Onsite Care (HIDOC) intensive primary care program implemented at a university clinic, comprising (a) care by an interprofessional team, (b) new logistical capacity, and (c) clinician skills training. Measured outcomes include Emergency Department (ED) visits and hospitalizations at a university and a community hospital over 2 years, using a within-subjects design. We demonstrate decreased hospitalizations at the University Hospital, and a decrease in ED visits at both sites. Team-based strategies to provide intensive primary care can decrease utilization, allowing for greater continuity of care.

eConsults' Impact on Care Access and Wait Times in Rheumatology.

BACKGROUND/OBJECTIVE: A growing number of health systems have implemented eConsults to improve access to specialty advice, but few studies have described their use in rheumatology or impact on visit wait times. We evaluated the uptake of an eConsult program and its impact on wait times for in-person rheumatology visits. METHODS: In this quality improvement project, we analyzed electronic health record data from 4 intervention clinics and 4 comparison clinics, 12 months before and after implementation of an eConsult program. We compared median wait time for rheumatology appointments using a pre-post difference-in-differences analysis and quantile regression, adjusting for patient age, race, sex, clinic pair, and primary insurance payer. We also interviewed 11 primary care providers from the intervention clinics and conducted a rheumatology provider focus group (n = 4) to elucidate experiences with the program. RESULTS: Rheumatologists recommended management in primary care or referral to another specialty for 41% of eConsults, reducing initial demand for in-person visits. The median wait times dropped in the intervention and the comparison clinics (42 and 25 days, respectively). Intervention clinic median wait time dropped 17 days more than comparison clinics, and this was nonstatistically significant (p = 0.089). eConsults fit provider care tasks best for triage or initial workup for diagnosis, and less well when tests required interpretation, or when back and forth communication was needed to manage the patient's condition. CONCLUSIONS: Implementation of eConsults for rheumatology was associated with reduced wait times for rheumatology appointments and supported primary care providers in the triage and workup for a substantial portion of patients.

Gene therapy for cystic fibrosis: new tools for precision medicine.

The discovery of the Cystic fibrosis (CF) gene in 1989 has paved the way for incredible progress in treating the disease such that the mean survival age of individuals living with CF is now ~58 years in Canada. Recent developments in gene targeting tools and new cell and animal models have re-ignited the search for a permanent genetic cure for all CF. In this review, we highlight some of the more recent gene therapy approaches as well as new models that will provide insight into personalized therapies for CF.

Use of Chronic Prescription Medications and Prevalence of Polypharmacy in Survivors of Childhood Cancer.

BACKGROUND: As survivors of childhood cancer age, development of cancer treatment-related chronic health conditions often occur. This study aimed to describe the pattern of chronic prescription medication use and identify factors associated with polypharmacy among survivors of childhood cancer. METHODS: This was a retrospective study conducted at the pediatric oncology long-term follow-up clinic in Hong Kong. Eligible subjects included survivors who were (1) diagnosed with cancer before 18 years old, (2) were at least 3 years post-cancer diagnosis and had completed treatment for at least 30 days, and (3) receiving long-term follow-up care at the study site between 2015 and 2018. Dispensing records of eligible survivors were reviewed to identify medications taken daily for ≥30 days or used on an "as needed" basis for ≥6 months cumulatively within the past 12-month period. Polypharmacy was defined as the concurrent use of ≥5 chronic medications. Multivariable log-binomial modeling was conducted to identify treatment and clinical factors associated with medication use pattern and polypharmacy. RESULTS: This study included 625 survivors (mean current age = 17.9 years, standard deviation [SD] = 7.2 years) who were 9.2 [5.2] years post-treatment. Approximately one-third (n = 219, 35.0%) of survivors were prescribed at least one chronic medication. Frequently prescribed medication classes include systemic antihistamines (26.5%), sex hormones (19.2%), and thyroid replacement therapy (16.0%). Overall prevalence of polypharmacy was 5.3% (n = 33). A higher rate of polypharmacy was found in survivors of CNS tumors (13.6%) than in survivors of hematological malignancies (4.3%) and other solid tumors (5.3%) (P = .0051). Higher medication burden was also observed in survivors who had undergone cranial radiation (RR = 6.31; 95% CI = 2.75-14.49) or hematopoietic stem-cell transplantation (HSCT) (RR = 3.53; 95% CI = 1.59-7.83). CONCLUSION: Although polypharmacy was observed in a minority of included survivors of childhood cancer, chronic medication use was common. Special attention should be paid to survivors of CNS tumors and survivors who have undergone HSCT or cranial radiation. These individuals should be monitored closely for drug-drug interactions and adverse health outcomes that may result from multiple chronic medications, particularly during hospitalization in an acute care setting.

Mapping Tonal Hierarchy in the Brain.

In Western tonal music, pitches are organized hierarchically based on their perceived fit in a specific tonal context. This hierarchy forms scales that are commonly used in Western tonal music. The hierarchical nature of tonal structure is well established behaviourally; however, the neural underpinnings are largely unknown. In this study, EEG data and goodness-of-fit ratings were collected from 34 participants who listened to an arpeggio followed by a probe tone, where the probe tone could be any chromatic scale degree and the context any of the major keys. Goodness-of-fit ratings corresponded to the classic tonal hierarchy. N1, P2 and the Early Right Anterior Negativity (ERAN) were significantly modulated by scale degree. Furthermore, neural marker amplitudes and latencies were significantly correlated with similar magnitude to both pitch height and goodness-of-fit ratings. This is different from the clearer divide between pitch height correlating with early neural markers (100-200 ms) and tonal hierarchy correlating with late neural markers (200-1000 ms) reported by Sankaran et al. (2020) and Quiroga-Martinez et al. (2019). Finally, individual differences were greater than any main effects detected when pooling participants and brain-behavior correlations vary widely (i.e. r = -0.8 to 0.8).

General Behavioral Engagement and Changes in Clinical and Cognitive Outcomes of Patients with Type 2 Diabetes Using the Time2Focus Mobile App for Diabetes Education: Pilot Evaluation.

BACKGROUND: Type 2 diabetes affects 30 million Americans, representing a significant cause of morbidity and mortality. Self-management support is an important component of chronic illness care and is a key pillar of the chronic care model. Face-to-face teaching and patient education materials suffer from being static or incompatible with mobile lifestyles. Digital apps provide a self-management support alternative that is convenient and scalable. OBJECTIVE: This pilot study tested the real-world deployment of a self-guided mobile app for diabetes education (Time2Focus app; MicroMass Communications Inc, Cary, NC), which utilizes evidence-based content and gamification to deliver an interactive learning experience. METHODS: Primary care providers were approached for permission to invite their patients to participate. Eligible patients were 18 to 89 years of age, had a diagnosis of type 2 diabetes, hemoglobin A1c (HbA1c) ≥8% and <12% in the past 3 months, an active online patient portal account (tied to the electronic health record), and access to an iOS or Android smartphone. Interested patients were emailed a baseline survey, and once this was completed, were sent instructions for downloading the Time2Focus app. After completing all 12 levels, participants were sent a follow-up survey. The primary outcome was the change in HbA1c. Secondary outcomes included medication adherence, self-care activities, self-reporting of physical activities, diabetes self-efficacy, illness perceptions, diabetes distress scale, and users' engagement with and rating of the app. RESULTS: Of 1355 potentially eligible patients screened, 201 were consented. Of these 201 patients, 101 (50.2%) did not download the app. Of the 100 participants (49.8%) who downloaded the app, 16 (16.0%) completed 0 levels, 26 (26.0%) completed 1 to 4 levels, 10 (10.0%) completed 5 to 11 levels, and 48 (48.0%) completed all 12 levels of the app and the follow-up survey. Those completing one or more levels had a mean pre/post-HbA1c change of -0.41% (compared to -0.32% among those who completed zero levels); however, the unadjusted two-tailed t test indicated no significant difference between the two groups (P=.73). Diabetes self-efficacy showed a large and significant increase during app usage for completers (mean change 1.28, P<.001, d=.83). Severity of illness perceptions showed a small but significant decrease during app usage for completers (mean change -0.51, P=.004, d=.43). Diabetes distress showed a small but significant decrease during app usage for completers (mean change -0.45, P=.006, d=.41). The net promoter score was 62.5, indicating that those who completed all levels of the app rated it highly and would recommend it to others. CONCLUSIONS: Participants who engaged in all 12 levels of the Time2Focus mobile app showed an improvement in diabetes self-efficacy and a decrease in severity of illness perceptions. The decrease in HbA1c observed in app users relative to nonusers during this limited pilot study was not statistically significant. However, uptake and application of lessons learned from self-management support may be delayed. Further research is needed to address how to increase engagement through self-management support and to investigate if follow up over a longer period demonstrates a significant change in outcomes such as HbA1c.

Comparative risk of musculoskeletal adverse reactions among new users of dipeptidyl peptidase-4 inhibitors: A retrospective cohort study.

Background: The effects of dipeptidyl peptidase-4 inhibitors (DPP4Is) on joint pain have been controversial. Objective: To assess the comparative musculoskeletal (MSk) risk of DPP4Is vs. non-DPP4Is. Methods: This study used a national claims database from January 2007 to December 2014. Exposure included the initiation of DPP4Is against the initiation of non-DPP4Is: metformin, sulfonylureas, thiazolidinediones, meglitinides, and glucagonlike peptide-1 receptor agonists (GLP-1 RAs). Insulin was not included in this study. Outcomes were newly diagnosed MSk conditions (arthralgia, arthropathy, and rheumatoid arthritis or other inflammatory polyarthropathies). Individuals exposed to DPP4Is were matched to those exposed to non-DPP4Is using a propensity score (PS). Balance between the DPP4I's group and the non-DPP4I's group was assessed using standardized differences for both continuous and categorical variables. Cox regressions were used to estimate hazard ratios (HRs) for MSk conditions. Results: Among PS-matched cohorts, incidence rates (IRs) for MSk conditions did not differ between DPP4I initiators and non-DPP4I initiators (HR = 1.01, 95% CI: 0.97-1.05). After stratifying non-DPP4Is by drug class, the results still showed that DPP4I initiators had similar MSk risk when compared to initiators of metformin, sulfonylureas, meglitinides, and GLP-1 RAs. However, thiazolidinedione initiators had higher risk of MSk conditions than DPP4I initiators (HR = 1.05, 95% CI: 1.00-1.10). Conclusions: This head-to-head comparison study estimated comparative MSk risks among different antidiabetic drugs. The risk of MSk conditions among DPP4I initiators were not significantly higher than non-DPP4I initiators.

Telehealth transformation: COVID-19 and the rise of virtual care.

The novel coronavirus disease-19 (COVID-19) pandemic has altered our economy, society, and healthcare system. While this crisis has presented the U.S. healthcare delivery system with unprecedented challenges, the pandemic has catalyzed rapid adoption of telehealth, or the entire spectrum of activities used to deliver care at a distance. Using examples reported by U.S. healthcare organizations, including ours, we describe the role that telehealth has played in transforming healthcare delivery during the 3 phases of the U.S. COVID-19 pandemic: (1) stay-at-home outpatient care, (2) initial COVID-19 hospital surge, and (3) postpandemic recovery. Within each of these 3 phases, we examine how people, process, and technology work together to support a successful telehealth transformation. Whether healthcare enterprises are ready or not, the new reality is that virtual care has arrived.

Tibial access for supra-inguinal embolization in extremely obese patients.

Extreme obesity is a risk factor for hemorrhagic complications of femoral access (FA). Femoral lines, hematomas, pelvic binders and coagulopathy in the trauma scenario may also add difficulty and/or risk to FA. Radial access (RA) for routine peripheral endovascular procedures has been popularized owing to decreased hemorrhagic complications, increased patient satisfaction, and decreased operator radiation dose. However, though uncommon, cerebrovascular complications from RA approach are a known risk. Relatively recently, tibial access (TA) has been used for lower extremity peripheral vascular disease interventions. The advantages of TA mirror that of RA, with few and mostly minor complications, and the risk of iatrogenic cerebral embolization is nil. We report the feasibility of TA for supra-inguinal embolization in two extremely obese patients {body mass index > 40 kg/m2} following motor vehicle accidents. Commercially available base and microcatheters were used to perform embolization of the affected lower abdominal or pelvic arteries in standard fashion via a novel trans-tibial artery approach.

Multiyear Outcomes of a Population-Oriented Care Redesign in an Internal Medicine Residency Continuity Clinic.

The cornerstone of ambulatory care training for internal medicine residents is the continuity clinic, which often serves medically and psychosocially complex patients. We conducted and evaluated a population-oriented redesign to improve care for "high-needs" patients and the resident experience at a hospital-based safety net primary care internal medicine practice in the Southeastern U.S. A Define, Measure, Analyze, Implement, Control (DMAIC) framework was adapted to identify and develop three main interventions to address major unmet needs of patients and trainees: (1) a behavioral health-focused team care model; (2) a formalized hospital discharge transitions workflow; and (3) the creation of larger "firms" of smaller resident practice partnerships. We constructed a financial model to justify investments, with metrics to track progress. Over three years, sustained reductions in hospitalizations and ED visits (mean annual changes of -11.6% and -16.9%, respectively) were achieved. Resident primary care provider (PCP)-to-patient continuity and satisfaction also improved.

Keeping care connected: e-Consultation program improves access to nephrology care.

INTRODUCTION: Health systems are seeking innovative solutions to improve specialty care access. Electronic consultations (eConsults) allow specialists to provide formal clinical recommendations to primary care providers (PCPs) based on patient chart review, without a face-to-face visit. METHODS: We implemented a nephrology eConsult pilot program within a large, academic primary care practice to facilitate timely communication between nephrologists and PCPs. We used primary care referral data to compare wait times and completion rates between traditional referrals and eConsults. We surveyed PCPs to assess satisfaction with the program. RESULTS: For traditional nephrology referrals placed during the study period (July 2016-March 2017), there was a 51-day median appointment wait time and a 40.9% referral completion rate. For eConsults, there was a median nephrologist response time of one day and a 100% completion rate; 67.5% of eConsults did not require a subsequent face-to-face specialty appointment. For eConsults that were converted to an in-person visit, the median wait time and completion rate were 40 days and 73.1%, respectively. Compared to traditional referrals placed during the study period, eConsults converted to in-person visits were more likely to be completed ( p = 0.001). Survey responses revealed that PCPs were highly satisfied with the program and consider the quick turnaround time as the greatest benefit. DISCUSSION: Our eConsult pilot program reduced nephrology wait times and significantly increased referral completion rates. In large integrated health systems, eConsults have considerable potential to improve access to specialty care, reduce unnecessary appointments, and optimize the patient population being seen by specialists.

Automated fabrication of photopatterned gelatin hydrogels for organ-on-chips applications.

Organ-on-chip platforms aim to improve preclinical models for organ-level responses to novel drug compounds. Heart-on-a-chip assays in particular require tissue engineering techniques that rely on labor-intensive photolithographic fabrication or resolution-limited 3D printing of micropatterned substrates, which limits turnover and flexibility of prototyping. We present a rapid and automated method for large scale on-demand micropatterning of gelatin hydrogels for organ-on-chip applications using a novel biocompatible laser-etching approach. Fast and automated micropatterning is achieved via photosensitization of gelatin using riboflavin-5'phosphate followed by UV laser-mediated photoablation of the gel surface in user-defined patterns only limited by the resolution of the 15 µm wide laser focal point. Using this photopatterning approach, we generated microscale surface groove and pillar structures with feature dimensions on the order of 10-30 µm. The standard deviation of feature height was 0.3 µm, demonstrating robustness and reproducibility. Importantly, the UV-patterning process is non-destructive and does not alter gelatin micromechanical properties. Furthermore, as a quality control step, UV-patterned heart chip substrates were seeded with rat or human cardiac myocytes, and we verified that the resulting cardiac tissues achieved structural organization, contractile function, and long-term viability comparable to manually patterned gelatin substrates. Start-to-finish, UV-patterning shortened the time required to design and manufacture micropatterned gelatin substrates for heart-on-chip applications by up to 60% compared to traditional lithography-based approaches, providing an important technological advance enroute to automated and continuous manufacturing of organ-on-chips.

Understanding Frequent Emergency Department Use Among Primary Care Patients.

Patients with high emergency department (ED) utilization are an important focus in population health management. This retrospective cohort study analyzed patterns of frequent ED use for 4087 patients enrolled at an academically-affiliated primary care clinic. For all ED visits (n = 4776), the chief complaints, admission rates, number of complaints per patient, and median time between return visits were assessed. Chart reviews were conducted for the 10 highest utilizers from each of the 3 leading complaints to help explain repeated ED use for the same complaints. Results showed that chief complaints for high utilizers were statistically similar to other patients. Nearly half (49.8%) of all ED visits among high utilizers were repeat visits for the same complaint. However, most high utilizers (85%) had 4 or more separate complaints. Their visits clustered temporally, with 55% occurring less than 30 days apart. Visits for psychiatric symptoms demonstrated the shortest time to repeat visit (median 17.5 days, interquartile range: 39.5). Abdominal pain, chest pain, and shortness of breath were the leading complaints and the leading sources of hospital admissions and repeat visits. Chart review revealed that these 3 chief complaints often were associated with a wide range of ongoing chronic conditions, confounded by substance abuse, anxiety, and treatment nonadherence. This study demonstrates an integrative method for examining patterns of ED use among high utilizers. It also highlights the complex nature of high utilization and the inherent difficulty in predicting and addressing the needs of high-utilizer patients.

Primary care providers' use of pharmacist support for delivery of pharmacogenetic testing.

AIM: To investigate provider utilization of pharmacist support in the delivery of pharmacogenetic testing in a primary care setting. METHODS: Two primary care clinics within Duke University Health System participated in the study between December 2012 and July 2013. One clinic was provided with an in-house pharmacist and the second clinic had an on-call pharmacist. RESULTS: Providers in the in-house pharmacist arm consulted with the pharmacist for 13 of 15 cases, or about one of every four patients tested compared with one of every 7.5 patients in the on-call pharmacist arm. A total of 63 tests were ordered, 48 by providers in the pharmacist-in-house arm. CONCLUSION: These findings suggest that the availability of an in-house pharmacist increases the likelihood of pharmacogenetic test utilization.

Impact of Genetic Testing and Family Health History Based Risk Counseling on Behavior Change and Cognitive Precursors for Type 2 Diabetes.

Family health history (FHH) in the context of risk assessment has been shown to positively impact risk perception and behavior change. The added value of genetic risk testing is less certain. The aim of this study was to determine the impact of Type 2 Diabetes (T2D) FHH and genetic risk counseling on behavior and its cognitive precursors. Subjects were non-diabetic patients randomized to counseling that included FHH +/- T2D genetic testing. Measurements included weight, BMI, fasting glucose at baseline and 12 months and behavioral and cognitive precursor (T2D risk perception and control over disease development) surveys at baseline, 3, and 12 months. 391 subjects enrolled of which 312 completed the study. Behavioral and clinical outcomes did not differ across FHH or genetic risk but cognitive precursors did. Higher FHH risk was associated with a stronger perceived T2D risk (pKendall < 0.001) and with a perception of "serious" risk (pKendall < 0.001). Genetic risk did not influence risk perception, but was correlated with an increase in perception of "serious" risk for moderate (pKendall = 0.04) and average FHH risk subjects (pKendall = 0.01), though not for the high FHH risk group. Perceived control over T2D risk was high and not affected by FHH or genetic risk. FHH appears to have a strong impact on cognitive precursors of behavior change, suggesting it could be leveraged to enhance risk counseling, particularly when lifestyle change is desirable. Genetic risk was able to alter perceptions about the seriousness of T2D risk in those with moderate and average FHH risk, suggesting that FHH could be used to selectively identify individuals who may benefit from genetic risk testing.

Patient experiences with pharmacogenetic testing in a primary care setting.

AIM: To investigate patient experiences with pharmacogenetic (PGx) testing. METHODS: Patients were offered PGx testing through a study on pharmacist-assisted delivery of PGx testing and invited to complete pre- and post-testing surveys about their experience. RESULTS: Of 63 patients tested, 17 completed the baseline survey (27%). Interest in testing was mostly impacted by desire to inform selection of best treatment (n = 13). Seven of 12 patients that completed the follow-up survey indicated that their provider discussed the test result with them. Five patients understood their test result very or somewhat well. All would be likely to have PGx testing again. CONCLUSION: Patients perceived PGx testing to be useful, though more effort may be needed to improve patient-provider communication of test results.

Does Type 2 Diabetes Genetic Testing and Counseling Reduce Modifiable Risk Factors? A Randomized Controlled Trial of Veterans.

OBJECTIVE: We examined the clinical utility of supplementing type 2 diabetes mellitus (DM) risk counseling with DM genetic test results and counseling. RESEARCH DESIGN AND METHODS: In this randomized controlled trial, non-diabetic overweight/obese veteran outpatients aged 21 to 65 years received DM risk estimates for lifetime risk, family history, and fasting plasma glucose, followed by either genetic test results (CR+G; N = 303) or control eye disease counseling (CR+EYE; N = 298). All participants received brief lifestyle counseling encouraging weight loss to reduce the risk of DM. RESULTS: The mean age was 54 years, 53% of participants were black, and 80% were men. There was no difference between arms in weight (estimated mean difference between CR+G vs. CR+EYE at 3 months = 0.2 kg, 95% CI: -0.3 to 0.7; at 6 months = 0.4 kg, 95 % CI: -0.3 to 1.1), insulin resistance, perceived risk, or physical activity at 3 or 6 months. Calorie and fat intake were lower in the CR+G arm at 3 months (p's ≤ 0.05) but not at 6 months (p's > 0.20). CONCLUSIONS: Providing patients with genetic test results was not more effective in changing patient behavior to reduce the risk of DM compared to conventional risk counseling. TRIAL REGISTRATION: ClinicalTrials.gov NCT01060540 http://clinicaltrials.gov/show/NCT01060540.