Oregon Health and Science University

Background: Sexual and gender minority (SGM) older adults and their care partners, compared to the general population, face unique vulnerabilities that exacerbate living with dementia, including elevated disparities in comorbidities, social isolation, and structural inequities, such as discrimination and lack of access to supports. Methods: This paper describes the virtual adaptation process of the first-ever randomized controlled clinical trial intervention, Aging with Pride: Innovations in Dementia Empowerment and Action (IDEA), that was designed for SGM older adults living with dementia and their care partners and built upon the foundation of RDAD and NHAS. Results: The virtual adaptation of IDEA was guided by the goals of accessibility, quality, ease of delivery, sustainability, and cultural relevance. The implementation required the development of a HIPPA-compliant online virtual platform, coach and participant virtual training, and modification of necessary intervention elements and materials, as needed. Based on the preliminary findings, the participants and intervention coaches responded well to the virtual adaptation of IDEA. When comparing to in-person delivery, the virtual delivery decreased attrition among both intervention participants and coaches. Discussion: The virtual adaptation of the IDEA intervention resulted in preliminary, unexpected, yet potentially important benefits, including the ability to expand the reach of the intervention and decreased attrition. Virtual interventions are an emerging field for people living with dementia and their care partners and additional systematic research is needed to fully assess the benefits and limitations as well as to evaluate if specific subgroups are better served by differing delivery modalities.

Background Prior research suggests that physicians' personal experience with breastfeeding may influence their attitudes toward breastfeeding. This phenomenon has not been explored in well‐newborn care physician leaders, whose administrative responsibilities often include drafting and approval of hospital breastfeeding and formula supplementation policies. Methods We conducted a mixed‐methods study, surveying physicians in the Better Outcomes through Research for Newborns (BORN) network. We examined physician attitudes toward recommending breastfeeding and their breastfeeding experience. Qualitative analysis was conducted on responses to the question: “How do you think your breastfeeding experience influences your clinical practice?” Results Of 71 participants, most (92%) had a very positive attitude toward breastfeeding with 75% of respondents reporting personal experience with breastfeeding. Of these, 68% had a very positive experience, 25% had a somewhat positive experience, and 6% had a neutral experience. Four themes emerged with respect to the effect of breastfeeding experience on practice: (1) empathy with breastfeeding struggles, (2) increased knowledge and skills, (3) passion for breastfeeding benefits, and (4) application of personal experience in lieu of evidence‐based medicine, particularly among those who struggled with breastfeeding. Conclusions Well‐newborn care physician leaders reported positive attitudes about breastfeeding, increased support toward breastfeeding persons, and a perception of improved clinical lactation skills. Those who struggled with breastfeeding reported increased comfort with recommending formula supplementation to their own patients. Medical education about evidence‐based breastfeeding support practices and provision of lactation support to physicians has the potential to affect public health through improved care for the patients they serve.

White matter connectivity supports diverse cognitive demands by efficiently constraining dynamic brain activity. This efficiency can be inferred from network controllability, which represents the ease with which the brain moves between distinct mental states based on white matter connectivity. However, it remains unclear how brain networks support diverse functions at birth, a time of rapid changes in connectivity. Here, we investigate the development of network controllability during the perinatal period and the effect of preterm birth in 521 neonates. We provide evidence that elements of controllability are exhibited in the infant’s brain as early as the third trimester and develop rapidly across the perinatal period. Preterm birth disrupts the development of brain networks and altered the energy required to drive state transitions at different levels. In addition, controllability at birth is associated with cognitive ability at 18 months. Our results suggest network controllability develops rapidly during the perinatal period to support cognitive demands but could be altered by environmental impacts like preterm birth.

Background Comorbid chronic rhinosinusitis (CRS) remains unresolved for many people with cystic fibrosis (PwCF). While highly effective modulator therapy improves quality‐of‐life and symptom severity, the impact of this intervention and other factors associated with pursuing endoscopic sinus surgery (ESS) remains understudied. Methods Adult PwCF + CRS were enrolled into a prospective, observational, multi‐institutional study. Participants completed validated outcome measures to evaluate respiratory symptom severity, depression, headache, and sleep quality, as well as nasal endoscopy, sinus computed tomography (CT), and olfactory testing. Bivariate comparisons and regression modeling evaluated treatment cofactors, disease characteristics, and outcome measures associated with pursuing ESS. Results Sixty PwCF were analyzed, including 24 (40%) who elected ESS. Pursuing ESS was associated with worse SinoNasal Outcome Test (SNOT‐22) total, rhinologic, psychological, and sleep dysfunction domain scores; worse Patient Health Questionnaire‐9‐Revised depression scores; worse Pittsburgh Sleep Quality Index total scores; worse weight, role, emotion, and eating domain scores on the Cystic Fibrosis Questionnaire‐Revised; more severe disease on nasal endoscopy; and lack of modulator therapy (all p < 0.050). Multivariable regression identified that worse SNOT‐22 total score was associated with electing ESS (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02–1.16, p = 0.015) and elexacaftor/tezacaftor/ivacaftor (ETI) treatment (OR 0.04, 95% CI 0.004–0.34, p = 0.004) was associated with pursing medical therapy. Conclusions Worse sinonasal symptom burden, lack of ETI treatment, sleep quality, depression, and nasal endoscopy scores were associated with electing ESS, while lung disease severity and sinus CT scores were not. ETI use was associated with lower odds of pursuing ESS independent of sinonasal symptom burden.

Background Upadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study. Methods Patients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks. Patients who completed 14 weeks could enter an open-label extension and receive upadacitinib 15 mg QD for up to 2 years. Efficacy endpoints included the percentage of patients achieving ≥ 40% improvement in Assessment of SpondyloArthritis international Society response (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA), and ASDAS inactive disease (ID); and change from baseline in total and nocturnal back pain, and Bath Ankylosing Spondylitis Functional Index (BASFI). Subgroup analyses (bDMARD lack of efficacy versus intolerance, and prior tumor necrosis factor inhibitor [TNFi] versus interleukin-17 inhibitor [IL-17i] exposure) were conducted. Binary and continuous efficacy endpoints were assessed using non-responder imputation with multiple imputation (NRI-MI) and as observed (AO) analyses; and mixed-effects model repeated measures (MMRM) and AO, respectively. Safety was assessed based on adverse events. Data through week 52 are reported. Results Of 420 randomized patients, 366 (continuous upadacitinib: n = 181; placebo to upadacitinib: n = 185) completed 52 weeks of treatment. At week 52, in the continuous upadacitinib and placebo to upadacitinib groups, ASAS40, ASDAS LDA, and ASDAS ID were achieved by 66% and 65%, 57% and 55%, and 26% and 25% (all NRI-MI); and change from baseline in total back pain, nocturnal back pain, and BASFI was -4.5 and -4.3, -4.6 and -4.4, and -3.6 and -3.5 (all MMRM), respectively. No new safety risks were identified. Subgroup analyses were consistent with the overall study population. Conclusions Upadacitinib 15 mg QD demonstrated sustained improvement up to 52 weeks in bDMARD-IR patients with AS. Efficacy was generally similar in patients with lack of efficacy versus intolerance to bDMARDs and prior TNFi versus IL-17i exposure. Trial registration NCT02049138.

Uniparental inheritance of mitochondrial DNA (mtDNA) is an evolutionary trait found in nearly all eukaryotes. In many species, including humans, the sperm mitochondria are introduced to the oocyte during fertilization1,2. The mechanisms hypothesized to prevent paternal mtDNA transmission include ubiquitination of the sperm mitochondria and mitophagy3,4. However, the causative mechanisms of paternal mtDNA elimination have not been defined5,6. We found that mitochondria in human spermatozoa are devoid of intact mtDNA and lack mitochondrial transcription factor A (TFAM)—the major nucleoid protein required to protect, maintain and transcribe mtDNA. During spermatogenesis, sperm cells express an isoform of TFAM, which retains the mitochondrial presequence, ordinarily removed upon mitochondrial import. Phosphorylation of this presequence prevents mitochondrial import and directs TFAM to the spermatozoon nucleus. TFAM relocalization from the mitochondria of spermatogonia to the spermatozoa nucleus directly correlates with the elimination of mtDNA, thereby explaining maternal inheritance in this species.

Body composition assessment is a valuable tool for clinical assessment and research that has implications for long‐term health. Unlike traditional measurements such as anthropometrics or body mass index, body composition assessments provide more accurate measures of body fatness and lean mass. Moreover, depending on the technique, they can offer insight into regional body composition, bone mineral density, and brown adipose tissue. Various methods of body composition assessment exist, including air displacement plethysmography, dual‐energy x‐ray absorptiometry, bioelectrical impedance, magnetic resonance imaging, D3 creatine, ultrasound, and skinfold thickness, each with its own strengths and limitations. In infants, several feeding practices and nutrition factors are associated with body composition outcomes, such as breast milk vs formula feeding, protein intake, breast milk composition, and postdischarge formulas for preterm infants. Longitudinal studies suggest that body composition in infancy predicts later body composition, obesity, and other cardiometabolic outcomes in childhood, making it a useful early marker of cardiometabolic health in both term and preterm infants. Emerging evidence also suggests that body composition during infancy predicts neurodevelopmental outcomes, particularly in preterm infants at high risk of neurodevelopmental impairment. The purpose of this narrative review is to provide clinicians and researchers with a comprehensive overview of body composition assessment techniques, summarize the links between specific nutrition practices and body composition in infancy, and describe the neurodevelopmental and cardiometabolic outcomes associated with body composition patterns in term and preterm infants.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and represents a significant global health burden. Management of HCC can be challenging due to multiple factors, including variable expectations for treatment outcomes. Several treatment options are available, each with specific eligibility and ineligibility criteria, and are provided by a multidisciplinary team of specialists. Radiologists should be aware of the types of treatment options available, as well as the criteria guiding the development of individualized treatment plans. This awareness enables radiologists to contribute effectively to patient-centered multidisciplinary tumor boards for HCC and play a central role in reassessing care plans when the treatment response is deemed inadequate. This comprehensive review aims to equip radiologists with an overview of HCC staging systems, treatment options, and eligibility criteria. The review also discusses the significance of imaging in HCC diagnosis, treatment planning, and monitoring treatment response. Furthermore, we highlight the crucial branch points in the treatment decision-making process that depend on radiological interpretation. Graphical abstract

The frequency of invasive fungal infections has risen dramatically in recent decades, mostly because of a larger population of at-risk patients who are immunocompromised, neutropenic, or critically ill. For clinicians evaluating these patients, it has become increasingly important to make the diagnosis early so that timely antifungal therapy can be instituted. While histopathology and culture for the causative fungus are required for a definitive diagnosis, adequate tissue samples from protected anatomical sites are not always available and culture may lack sensitivity and require several weeks for results to become available. Thus, immunodiagnosis has become an important adjunctive strategy to diagnose most of the clinically relevant fungi. Many immunodiagnostic methods have been developed and generally target three important aspects of the infection: host antibody, fungal antigen, and fungal metabolites. This chapter outlines the available immunologic tests according to what component of the invading pathogen or host immune response they target and provides some discussion of their strengths and weaknesses. In addition to a review of pan-fungal testing using 1,3-β-D-glucan, the discussion is focused on the following diseases: invasive candidiasis, invasive aspergillosis, cryptococcosis, histoplasmosis, blastomycosis, coccidioidomycosis, and paracoccidioidomycosis. Recommendations for utilizing the currently available immunodiagnostic tests are discussed for individual fungal species and specific disease manifestations.

Purpose: This cross-sectional study aimed to investigate the sectoral variance of optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters across eyes with varying degrees of refractive error. Methods: Healthy participants, including individuals with axial ametropia, enrolled in the Hong Kong FAMILY cohort were imaged using the Avanti/AngioVue OCT/OCTA system. The OCT and OCTA parameters obtained include peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), and macular ganglion cell complex thickness (GCCT). Sectoral measurements of NFLT, NFLP-CD, and GCCT were based on sectors and hemispheres. Results: A total of 1339 eyes from 791 participants were stratified based on spherical equivalent refraction: high myopia (<−6 D), low myopia (−6 D to −1 D), emmetropia (−1 D to 1 D), and hyperopia (>1 D). Multivariable broken stick regression models, accounting for age, sex, and signal strength, showed that all NFLT sectors except temporally, the inferior GCCT hemisphere, and half of the NFLP-CD sectors were more affected by ametropia-related covariates than the corresponding global parameters. As expected, the false-positive rates in those sectors were elevated. Finally, sector-specific axial length (AL) and spherical equivalent (SE) adjustments helped reduce the elevated false-positive rates. Conclusions: The effect of optical magnification is even more prominent among sectors than the global parameters. AL-and SE-based adjustments should be individualized to each sector to mitigate this magnification bias effectively. Translational Relevance: Identifying sectoral differences among diagnostic parameters and adopting these sector-based adjustments into commercial OCT systems will hopefully reduce false-positive rates related to refractive error.

Aim The aim of this study was to estimate how ongoing stimulant use affects return to illicit opioid use after initiation onto medication for opioid use disorder (MOUD). Design This was a secondary analysis of pooled data from two clinical trials comparing buprenorphine (BUP‐NX) and extended‐release naltrexone (XR‐NTX). Setting Thirteen opioid treatment programs and HIV clinics across 10 states in the United States from 2014 to 2019 took part in this study. Participants A total of 528 participants who initiated MOUD as part of trial participation were included. Nearly half (49%) were between 30 and 49 years of age, 69% were male and 66% were non‐Hispanic White. Measurements The primary outcome was first self‐reported day of non‐prescribed opioid use following MOUD initiation, and the exposure of interest was daily stimulant use (methamphetamine, amphetamines or cocaine). Both were defined using time‐line follow‐back. Among participants reporting at least 1 day of illicit opioid use, we also examined relapse to ongoing use, defined as (1) 7 days of continuous opioid use or (2) 4 consecutive weeks with self‐reported opioid use, one or more positive urine drug screens (UDS) for opioids or one or more missing UDS. Findings Forty‐seven per cent of participants reported stimulant use following MOUD initiation, 58% returned to illicit opioid use and 66% of those relapsed to ongoing use. Stimulant use was strongly associated with increased risk of misusing opioids after MOUD initiation when measured daily [adjusted hazard ratio (aHR) = 9.23, 95% confidence interval (CI) = 6.80–12.50, P < 0.001] and over a 7‐day period (aHR = 1.27 for each additional day, CI = 1.18–1.37, P < 0.001). Using stimulants weekly or more often was associated with increased likelihood of relapse to ongoing opioid use compared with less than weekly or no stimulant use (adjusted odds ratio = 2.30, CI = 1.05–5.39, P = 0.044). Conclusions People initiated on medication for opioid use disorder who subsequently use stimulants appear to be more likely to return to and continue using non‐prescribed opioids compared with those without stimulant use. The association appears to be stronger among patients who initiate buprenorphine compared with those who initiate extended‐release naltrexone.

Purpose Lung cancer is the leading cause of cancer death, but the advent of lung cancer screening using low-dose computed tomography offers a tremendous opportunity to improve lung cancer outcomes. Unfortunately, implementation of lung cancer screening has been hampered by substantial barriers and remains suboptimal. Specifically, the commentary emphasizes the intersectionality of smoking history and several important sociodemographic characteristics and identities that should inform lung cancer screening outreach and engagement efforts, including socioeconomic considerations (e.g., health insurance status), racial and ethnic identity, LGBTQ + identity, mental health history, military experience/veteran status, and geographic residence in addressing specific community risk factors and future interventions in efforts to make strides toward equitable lung cancer screening. Methods Members of the Equitable Implementation of Lung Cancer Screening Interest Group with the Cancer Prevention and Control Network (CPCRN) provide a critical commentary based on existing literature regarding smoking trends in the US and lung cancer screening uptake to propose opportunities to enhance implementation and support equitable distribution of the benefits of lung cancer screening. Conclusion The present commentary utilizes information about historical trends in tobacco use to highlight opportunities for targeted outreach efforts to engage communities at high risk with information about the lung cancer screening opportunity. Future efforts toward equitable implementation of lung cancer screening should focus on multi-level implementation strategies that engage and work in concert with community partners to co-create approaches that leverage strengths and reduce barriers within specific communities to achieve the potential of lung cancer screening.

Introduction For liver stereotactic body radiation therapy (SBRT), the placement of fiducial markers or retained ethiodized oil by transarterial chemoembolisation (TACE) provides a landmark for consistent target localisation. TACE and fiducial markers are invasive procedures that harbour additional risks. We hypothesise that liver SBRT can be accurately delivered without the use of these invasive surrogate markers. Methods We retrospectively identified 50 consecutive patients who underwent liver SBRT with respiratory motion management to a single lesion which exhibited retained ethiodized oil per prior TACE delivery. For each SBRT fraction, two manual rigid image registrations were performed by the treating physician. One using the liver contour as a surrogate for the target and second aligning only to the radio‐opaque retained ethiodized oil of the treated lesion. The magnitude of the displacement vector between the two registration methods was used to assess the accuracy of target localisation if ethiodized oil was not present. Results For the 50 patients, a total of 244 analysable cone‐beam CTs (CBCTs) were included (six CBCTs excluded due to poor ethiodized oil visualisation). Respiratory motion management techniques consisted of active breathing control for 13 and abdominal compression for 37 patients. Forty‐two patients had peripheral lesions and eight had central lesions (<2 cm from left and right portal veins). The average target localisation offset between the two registration methods (i.e. liver contour vs. retained ethiodized oil alignment) for patients with a single peripheral or central liver lesion was 5.8 and 5.3 mm, respectively. Conclusions Across all patients, the average change in target position exceeded 5 mm for image registration methods based on the liver contour alone versus the retained ethiodized oil region. This suggests that margins greater than 5 mm may be required for respiratory motion‐managed liver SBRT treatments in patients who do not undergo prior TACE or fiducial placement.

Background Therapeutic use of cannabis is common in the United States (up to 18.7% of Americans aged ≥12), and dispensaries in the US are proliferating rapidly. However, the efficacy profile of medical cannabis is unclear, and customers often rely on dispensary staff for purchasing decisions. The objective was to describe cannabis dispensary staff perceptions of medical cannabis benefits and risks, as well as its safety in high-risk populations. Methods Online Survey study conducted using Qualtrics from February 13, 2020 to October 2, 2020 with a national sample of dispensary staff who reportedinteracting with customers in a cannabis dispensary selling tetrahydrocannabinol-containing products. Participants were queried about benefits (“helpfulness”) and risks (“worry”) about cannabis for a variety of medical conditions, and safety in older adults and pregnant women on a five-point Likert scale. These results were then collapsed into three categories including “neutral” (3/5). “I don’t know” (uncertainty) was a response option for helpfulness and safety. Results Participants (n = 434) were from 29 states and included patient-facing dispensary staff (40%); managers (32%); pharmacists (13%); and physicians, nurse practitioners, or physician assistants (5%). Over 80% of participants perceived cannabis as helpful for post-traumatic stress disorder (88.7%), epilepsy (85.3%) and cancer (83.4%). Generally, participants were not concerned about potential cannabis risks, including increased use of illicit drugs (76.3%), decreases in intelligence (74.4%), disrupted sleep (71.7%), and new/worsening health problems from medical cannabis use (70.7%). Cannabis was considered safe in older adults by 81.3% of participants, though there was much less consensus on safety in pregnancy. Conclusions Cannabis dispensary staff generally view medical cannabis as beneficial and low-risk. However, improvements in dispensary staff training, an increased role for certifying clinicians, and interventions to reduce dispensary staff concerns (e.g., cost, judgment) may improve evidence-based staff recommendations to patients seeking medical cannabis.

BACKGROUND Tranexamic acid (TXA) is increasingly being used to prevent hemorrhagic complications after dermatologic surgery. Interpolated flap repairs following Mohs micrographic surgery are at risk for increased bleeding events and unplanned health care utilization, particularly among patients on antithrombotic medication. OBJECTIVE To assess bleeding events after interpolated flap repair in patients receiving TXA compared with those who did not. MATERIALS AND METHODS A retrospective review identified interpolated flap repairs in a 5-year period. Hemorrhagic complications were analyzed, defined as major bleeding events, which included all unplanned medical visits, and minor bleeding events, which included any unplanned patient phone calls or messages through electronic medical record. RESULTS One hundred fifteen patients had interpolated flap repair during the 5-year period, of which 21 (18.3%) received TXA postprocedure. Twenty-seven bleeding events were identified in the non-TXA group compared with 1 event in the TXA-treated group. Patients who received TXA were less likely to have had a bleeding event (28.7% vs 4.8%, p < .01). CONCLUSION Patients undergoing interpolation flap repair were less likely to experience a bleeding event after subcutaneous injection of TXA.

Eating disorders and disordered eating are well-established medical and psychiatric conditions in athletics. Historically, the eating disorder focus has been primarily upon white cisgender female athletes, though emerging research has also described an increased prevalence of eating disorders in white cisgender male athletes. Additional work is ongoing regarding the unique challenges facing BIPOC and transgender/gender nonconforming athletes with eating disorders. Eating disorders and subclinical disordered eating behavior often “hide in plain sight” and may elude detection. As providers in sport, there is a need for increased proficiency at recognizing signs of disordered eating, awareness of our assumptions about eating disorders, vigilance for common co-morbidities, and prompt diagnosis of eating disorders and variants when appropriate. This chapter describes features of eating disorders in sports, highlights common comorbidities and risk factors for the development of eating disorders, and emphasizes the importance of an interdisciplinary approach for management and treatment of the afflicted individual.

Background and Objectives: Research on preparedness for independent clinical practice typically uses surveys of residents and program directors near graduation, which can be affected by several biases. We developed a novel approach to assess new graduates more objectively using physician and staff member assessors 3 months after graduates started their first job. Methods: We conducted a literature review and key informant interviews with physicians from varying practice types and geographic regions in the United States to identify features that indicate a lack of preparedness for independent clinical practice. We then held a Clinical Preparedness Measurement Summit, engaging measurement experts and family medicine education leaders, to build consensus on key indicators of readiness for independent clinical practice and survey development strategies. The 2015 entrustable professional activities for family medicine end-of-residency training provided the framework for assessment of clinical preparedness by physician assessors. Sixteen published variables assessing interpersonal communication skills and processes of care delivery were identified for staff assessors. We assessed frequencies and compared survey findings between physician and staff assessors in 2016 to assist with survey validation. Results: The assessment of frequencies demonstrated a range of responses, supporting the instrument’s ability to distinguish readiness for independent practice of recent graduate hires. No statistical differences occurred between the physician and staff assessors for the same physician they were evaluating, indicating internal consistency. Conclusions: To learn about the possible impact of length of training, we developed a novel approach to assess preparedness for independent clinical practice of family medicine residency graduates.