Dispositional traits help explain individual differences in relationships between a radiographic knee osteoarthritis measure, pain, and physical function.

Background: The concordance between radiograph-derived Kellgren-Lawrence (KL) scores for knee osteoarthritis (KOA) and experimental and clinical pain and KOA-related physical function is conflicting. Objectives: We investigate whether the inclusion of dispositional traits reduces variability between KOA radiographic findings, experimental pain, clinical pain, and function in individuals with knee pain. Design: This study is a cross-sectional, secondary analysis of data collected from the UPLOAD-II study. Methods: Adults aged 45-85 years with and without knee pain were enrolled. Data collected included sociodemographics, knee radiographs, experimental pain, clinical pain and function, and trait affect. Vulnerable and protective dispositional traits were classified from combined positive and negative trait affect measures. KL scores were determined from the knee radiographs. Unadjusted and adjusted (age, sex, comorbidities, and body mass index) regression analyses were completed with SAS version 9.4 (Cary, NC, USA). Results: The study included 218 individuals with a mean age of 58 years, 63.6% women, and 48.2% non-Hispanic black adults. Dispositional traits were associated with the experimental pain measures. No association between radiographic KOA and experimental pain was observed. In a combined and adjusted analysis, dispositional traits were predictive of knee punctate pain temporal summation (p = 0.0382). Both dispositional traits and radiographic KOA scores independently and combined were predictive of Graded Chronic Pain Scale pain and function, and Western Ontario and McMaster University pain and function (ps ⩽ 0.01). Improvements in R2 were noted across all models with the inclusion of dispositional traits. Conclusion: Consideration of dispositional traits reduces the variability between radiographic KOA and pain and function. Non-pathological and associated pain-related psychological factors and dispositional traits might serve as parsimonious proxy tools to improve clinical assessments. Registration: N/A.

Dispositional traits help explain individual differences in relationships between a radiographic knee osteoarthritis measure, pain, and physical function Significance • The concordance between radiographic knee osteoarthritis and experimental and clinical pain is conflicting. • Dispositional traits comprise the infrastructure from which an individual interprets and interacts with the environment and are predictive of sensory sensitivity, response to stress, psychopathology, and behavior. • Consideration of dispositional traits improves the congruence between knee osteoarthritis Kellgren-Lawrence scores, experimental pain, and clinical pain.

Harmonized Multisite MRI-Based Quantification of Human Liver Fat and Stiffness: A Pilot Study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of end-stage liver disease. NAFLD diagnosis and follow-up relies on a combination of clinical data, liver imaging, and/or liver biopsy. However, intersite imaging differences impede diagnostic consistency and reduce the repeatability of the multisite clinical trials necessary to develop effective treatments. PURPOSE/HYPOTHESIS: The goal of this pilot study was to harmonize commercially available 3 T magnetic resonance imaging (MRI) measurements of liver fat and stiffness in human participants across academic sites and MRI vendors. STUDY TYPE: Cohort. SUBJECTS: Four community-dwelling adults with obesity. FIELD STRENGTH/SEQUENCE: 1.5 and 3 T, multiecho 3D imaging, PRESS, and GRE. ASSESSMENT: Harmonized proton density fat fraction (PDFF) and magnetic resonance spectroscopy (MRS) protocols were used to quantify the FF of synthetic phantoms and human participants with obesity using standard acquisition parameters at four sites that had four different 3 T MRI instruments. In addition, a harmonized magnetic resonance elastography (MRE) protocol was used to quantify liver stiffness among participants at two different sites at 1.5 and 3 T field strengths. Data were sent to a single data coordinating site for postprocessing. STATISTICAL TESTS: Linear regression in MATLAB, ICC analyses using SAS 9.4, one-sided 95% confidence intervals for the ICC. RESULTS: PDFF and MRS FF measurements were highly repeatable among sites in both humans and phantoms. MRE measurements of liver stiffness in three individuals at two sites using one 1.5 T and one 3 T instrument showed repeatability that was high although lower than that of MRS and PDFF. CONCLUSIONS: We demonstrated harmonization of PDFF, MRS, and MRE-based quantification of liver fat and stiffness through synthetic phantoms, traveling participants, and standardization of postprocessing analysis. Multisite MRI harmonization could contribute to multisite clinical trials assessing the efficacy of interventions and therapy for NAFLD. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Greater socioenvironmental risk factors and higher chronic pain stage are associated with thinner bilateral temporal lobes.

INTRODUCTION: Previous research indicates ethnic/race group differences in pain and neurodegenerative diseases. Accounting for socioenvironmental factors reduces ethnic/race group differences in clinical and experimental pain. In the current study sample, we previously reported that in individuals with knee pain, ethnic/race group differences were observed in bilateral temporal lobe thickness, areas of the brain associated with risk for Alzheimer's disease, and related dementias. The purpose of the study was to determine if socioenvironmental factors reduce or account for previously observed ethnic/race group differences and explore if a combined effect of socioenvironmental risk and chronic pain severity on temporal lobe cortices is evident. METHODS: Consistent with the prior study, the sample was comprised of 147 adults (95 women, 52 men), 45-85 years of age, who self-identified as non-Hispanic Black (n = 72) and non-Hispanic White (n = 75), with knee pain with/at risk for osteoarthritis. Measures included demographics, health history, pain questionnaires, cognitive screening, body mass index, individual- and community-level socioenvironmental factors (education, income, household size, marital and insurance status, and area deprivation index), and brain imaging. We computed a summative socioenvironmental risk index. RESULTS: Regression analyses showed that with the inclusion of socioenvironmental factors, the model was significant (p < .001), and sociodemographic (ethnic/race) group differences were not significant (p = .118). Additionally, findings revealed an additive stress load pattern indicating thinner temporal lobe cortices with greater socioenvironmental risk and chronic pain severity (p = .048). IMPLICATIONS: Although individual socioenvironmental factors were not independent predictors, when collectively combined in models, ethnic/race group differences in bilateral temporal lobe structures were not replicated. Further, combined socioenvironmental risk factors and higher chronic pain severity were associated with thinner bilateral temporal lobes.

Medical and psychosocial outcomes of state-funded population genomic screening.

As the uptake of population screening expands, assessment of medical and psychosocial outcomes is needed. Through the Alabama Genomic Health Initiative (AGHI), a state-funded genomic research program, individuals received screening for pathogenic or likely pathogenic variants in 59 actionable genes via genotyping. Of the 3874 eligible participants that received screening results, 858 (22%) responded to an outcomes survey. The most commonly reported motivation for seeking testing through AGHI was contribution to genetic research (64%). Participants with positive results reported a higher median number of planned actions (median = 5) due to AGHI results as compared to negative results (median = 3). Interviews were conducted with survey participants with positive screening results. As determined by certified genetic counselors, 50% of interviewees took appropriate medical action based on their result. There were no negative or harmful actions taken. These findings indicate population genomic screening of an unselected adult population is feasible, is not harmful, and may have positive outcomes on participants now and in the future; however, further research is needed in order to assess clinical utility.

Pain Catastrophizing and Impact on Pelvic Floor Surgery Experience.

IMPORTANCE: Understanding patients' perceptions of symptoms and outcomes of urogynecologic surgery is essential for providing high-quality care. OBJECTIVE: The aim of the study was to assess association of pain catastrophizing with pelvic floor symptom distress and impact, postoperative pain, and voiding trial in patients undergoing urogynecologic surgery. STUDY DESIGN: Individuals whose self-identified gender was female and were undergoing surgery March 2020-December 2021 were included. Participants completed the Pain Catastrophizing Scale (range 0-52), Pelvic Floor Distress Inventory, and Pelvic Floor Impact Questionnaire preoperatively. Pain catastrophizing was score ≥30 and describes the tendency to magnify the overall threat of pain. Voiding trial failure was inability to void ≥2/3 of instilled volume (≤300 mL). The association between pain catastrophizing and symptom distress and impact was assessed with linear regression. A P < 0.05 is significant. RESULTS: Three hundred twenty patients were included (mean age, 60 years, 87% White). Forty-six of 320 participants (14%) had a pain catastrophizing score ≥30. The pain catastrophizing group had higher body mass index (33 ± 12 vs 29 ± 5), more benzodiazepine use (26% vs 12%), greater symptom distress (154 ± 58 vs 108 ± 60), and greater urogenital (59 ± 29 vs 47 ± 28), colorectal (42 ± 24 vs 26 ± 23), and prolapse (54 ± 24 vs 36 ± 24) subscale scores, all P ≤ 0.02. The pain catastrophizing group had greater impact (153 ± 72 vs 72 ± 64, P < 0.01) and urogenital (60 ± 29 vs 34 ± 28), colorectal (36 ± 33 vs 16 ± 26), and prolapse (57 ± 32 vs 22 ± 27) subscale scores, P < 0.01. Associations remained controlling for confounders ( P < 0.01). The pain catastrophizing group had higher 10-point pain scores (8 vs 6, P < 0.01) and was more likely to report pain at 2 weeks (59% vs 20%, P < 0.01) and 3 months (25% vs 6%, P = 0.01). Voiding trial failure did not differ (26% vs 28%, P = 0.98). CONCLUSIONS: Pain catastrophizing is associated with greater pelvic floor symptom distress and impact and postoperative pain but not voiding trial failure.

Biological Effective Radiation Dose for Multiple Myeloma Palliation.

Purpose: Various radiation therapy (RT) dose/fractionation schedules are acceptable for palliation in multiple myeloma. Nine years of single-institution RT experience were reviewed to determine the influence of dose/fractionation and other factors pertinent to individualizing therapy. Methods and Materials: In total, 152 items were identified from Current Procedural Terminology codes for multiple myeloma treatment from 2012 through June 30, 2021. After exclusions, 205 sites of radiation in 94 patients were reviewed. Data were captured from treatment planning and clinical records. To statistically assess the association between biological effective dose (BED10) and variables of interest, BED was first dichotomized to <24 Gy versus ≥24 Gy. Multivariate analysis used SAS software and a generalized estimating equation approach to account for multiple observations per patient. Results: Fractions of 1.8 to 8 Gy were used in 1 to 25 fractions. Most patients had no significant toxicity. Grade 1 toxicity was more likely with greater BED radiation courses, as expected (20% vs 12% for BED <24 Gy). Pain relief was complete or very good for most sites, with <3% reporting no pain relief. Eleven sites in 9 patients required retreatment. All retreatment sites had palliation that was lasting, with a median of 22 months to last follow-up or death after repeat course (range, 0.5-106 months). There was a trend for better pain control and less risk of fracture retreatment with BED ≥24 Gy. Conclusions: Most patients had good palliation without toxicity. BED ≥24 Gy caused 8% greater risk of grade 1 toxicity and trended toward better pain control plus reduced risk of fracture retreatment.

Longitudinal Changes of Bruch's Membrane Opening, Anterior Scleral Canal Opening, and Border Tissue in Experimental Juvenile High Myopia.

Purpose: To investigate the relative positional changes between the Bruch's membrane opening (BMO) and the anterior scleral canal opening (ASCO), and border tissue configuration changes during experimental high myopia development in juvenile tree shrews. Methods: Juvenile tree shrews were assigned randomly to two groups: binocular normal vision (n = 9) and monocular -10 D lens treatment starting at 24 days of visual experience to induce high myopia in one eye while the other eye served as control (n = 12). Refractive and biometric measurements were obtained daily, and 48 radial optical coherence tomography B-scans through the center of the optic nerve head were obtained weekly for 6 weeks. ASCO and BMO were segmented manually after nonlinear distortion correction. Results: Lens-treated eyes developed high degree of axial myopia (-9.76 ± 1.19 D), significantly different (P < 0.001) from normal (0.34 ± 0.97 D) and control eyes (0.39 ± 0.88 D). ASCO-BMO centroid offset gradually increased and became significantly larger in the experimental high myopia group compared with normal and control eyes (P < 0.0001) with an inferonasal directional preference. The border tissue showed a significantly higher tendency of change from internally to externally oblique configuration in the experimental high myopic eyes in four sectors: nasal, inferonasal, inferior, and inferotemporal (P < 0.005). Conclusions: During experimental high myopia development, progressive relative deformations of ASCO and BMO occur simultaneously with changes in border tissue configuration from internally to externally oblique in sectors that are close to the posterior pole (nasal in tree shrews). These asymmetric changes may contribute to pathologic optic nerve head remodeling and an increased risk of glaucoma later in life.

Morphology and morphometry of the human obturator nerve in males and females.

Peripheral nerve injury and the nerves' subsequent repair and regeneration continues to be marked clinically by poor functional recovery. The analysis of nerve morphology is an aspect which may provide an impact on successful clinical outcomes through better prediction of donor and recipient matching. In this study, we evaluated the morphological aspects of the human obturator nerve for a better understanding of its potential in nerve transplantation. Morphological characteristics of donor obturator nerves were analysed, including nerve diameter and length, fascicle count and the ratio of neural to non-neural tissue present within the cross-sectional area of the nerve's epineurium, with respect to laterality and sex. Statistical significance (p < 0.10) was determined for male obturator nerves having an average diameter of 2.67 mm compared to female obturator nerves at 1.91 mm, as well as left obturator nerves having an average of 11.21 fascicles compared to the right having an average of 10.17 fascicles. Strong positive correlations were determined between cross-sectional nerve area and limb size index, as well as between percentage of non-neural tissue and area of non-neural tissue, among males. Separately, strong correlation between percentage of non-neural tissue and area of non-neural tissue among right obturator nerves in males and females was determined . These findings indicate that there are associations and predictions that can be made about nerve morphology and that these when combined with other patient characteristics may enhance patient functional recovery following a peripheral nerve's repair.

Characteristics Associated With Postoperative Catheterization at Discharge in Women Undergoing Colpocleisis.

IMPORTANCE: Although transient voiding dysfunction is common after surgical correction of pelvic organ prolapse, it has not been well studied in women undergoing colpocleisis. OBJECTIVE: This study aimed to identify characteristics associated with discharge home with a urinary catheter in women undergoing colpocleisis. STUDY DESIGN: This is a secondary analysis of a multicenter prospective study examining the effect of pelvic support, symptoms, and satisfaction in women undergoing colpocleisis. Publicly accessible deidentified data sets of the index study were analyzed. Primary outcome was discharge with a urinary catheter postoperatively. Characteristics associated with discharge with catheter after colpocleisis were assessed via logistic regression. Covariates were selected based on statistical significance at 0.05 and clinical relevance on bivariate analysis. RESULTS: Of the 136 women (mean age, 77.8 ± 5.5 years) undergoing colpocleisis in the index study, 68 (50.0%) were discharged with catheter. Baseline characteristics did not differ, except that the catheter group had lower prior incontinence surgery (7.4% vs 22.1%, P = 0.02) and higher preoperative postvoid residual volume (PVR; 189.8 ± 187.6 vs 91.3 ± 124.2 mL, P < 0.01). Those discharged with catheter had greater estimated blood loss (128.7 ± 88.5 vs 95.3 ± 74.5 mL, P = 0.02), operative time (125.2 ± 56.3 vs 100.8 ± 45.4 minutes, P < 0.01), and concomitant levator myorrhaphy (82.4% vs 58.8%, P < 0.01). Multivariable analysis revealed preoperative PVR (adjusted odds ratio, 1.2; 95% confidence interval, 1.0-1.4 for every 50-mL increase in PVR) and levator myorrhaphy (adjusted odds ratio, 4.3; 95% confidence interval, 1.6-11.3) were associated with postoperative catheterization. CONCLUSIONS: In women undergoing colpocleisis, higher preoperative PVR and levator myorrhaphy were associated with discharge with catheter.

Extra-Virgin Olive Oil Enhances the Blood-Brain Barrier Function in Mild Cognitive Impairment: A Randomized Controlled Trial.

Mild cognitive impairment (MCI) and early Alzheimer's disease (AD) are characterized by blood-brain barrier (BBB) breakdown leading to abnormal BBB permeability ahead of brain atrophy or dementia. Previous findings in AD mouse models have reported the beneficial effect of extra-virgin olive oil (EVOO) against AD, which improved BBB and memory functions and reduced brain amyloid-ß (Aß) and related pathology. This work aimed to translate these preclinical findings to humans in individuals with MCI. We examined the effect of daily consumption of refined olive oil (ROO) and EVOO for 6 months in MCI subjects on BBB permeability (assessed by contrast-enhanced MRI), and brain function (assessed using functional-MRI) as the primary outcomes. Cognitive function and AD blood biomarkers were also assessed as the secondary outcomes. Twenty-six participants with MCI were randomized with 25 participants completed the study. EVOO significantly improved clinical dementia rating (CDR) and behavioral scores. EVOO also reduced BBB permeability and enhanced functional connectivity. While ROO consumption did not alter BBB permeability or brain connectivity, it improved CDR scores and increased functional brain activation to a memory task in cortical regions involved in perception and cognition. Moreover, EVOO and ROO significantly reduced blood Aß42/Aß40 and p-tau/t-tau ratios, suggesting that both altered the processing and clearance of Aß. In conclusion, EVOO and ROO improved CDR and behavioral scores; only EVOO enhanced brain connectivity and reduced BBB permeability, suggesting EVOO biophenols contributed to such an effect. This proof-of-concept study justifies further clinical trials to assess olive oil's protective effects against AD and its potential role in preventing MCI conversion to AD and related dementias.

COVID-19 Vaccine Knowledge, Attitudes, and Practices in Alabama: The Case for Primary Health Care Providers.

OBJECTIVE: To examine knowledge, attitudes, and practices about COVID-19 in Alabama, with a primary focus on vaccination perception and utilization. DESIGN: We used a COVID-19 Knowledge, Attitudes, and Practices survey and recruited adult Alabama residents in April-May 2021. PARTICIPANTS: Initial surveys from 1324 Alabamian participants were considered for analysis; after careful review of incomplete responses, 953 were ultimately included for analysis. MAIN OUTCOME MEASURE: Vaccine behavior and hesitancy comprise a self-reported response contained in the survey instrument. Three primary vaccine groups were used to assess differences in demographic characteristics, health status, perception of susceptibility and severity of COVID-19, sources of information, and trust about COVID-19. RESULTS: Of the 953 survey participants included for analysis, 951 had self-identified vaccine status in which 153 (16.1%) reported to have received the vaccine at the time of the survey, 375 (39.4%) were very likely or somewhat likely to get an approved COVID-19 vaccine if it was offered, and 423 (44.5%) were somewhat unlikely or very unlikely to get an approved COVID-19 vaccine. Health care providers were the most trusted sources of information, regardless of vaccine status. For participants unlikely to receive a vaccine, social media and local news sources were consistently more trusted and utilized than those who were vaccinated or were likely to be. CONCLUSIONS: The perceptions among unvaccinated participants are actionable and provide teachable opportunities to decrease vaccine apprehension.

Genetic regulation of OAS1 nonsense-mediated decay underlies association with COVID-19 hospitalization in patients of European and African ancestries.

The chr12q24.13 locus encoding OAS1-OAS3 antiviral proteins has been associated with coronavirus disease 2019 (COVID-19) susceptibility. Here, we report genetic, functional and clinical insights into this locus in relation to COVID-19 severity. In our analysis of patients of European (n = 2,249) and African (n = 835) ancestries with hospitalized versus nonhospitalized COVID-19, the risk of hospitalized disease was associated with a common OAS1 haplotype, which was also associated with reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) clearance in a clinical trial with pegIFN-λ1. Bioinformatic analyses and in vitro studies reveal the functional contribution of two associated OAS1 exonic variants comprising the risk haplotype. Derived human-specific alleles rs10774671-A and rs1131454 -A decrease OAS1 protein abundance through allele-specific regulation of splicing and nonsense-mediated decay (NMD). We conclude that decreased OAS1 expression due to a common haplotype contributes to COVID-19 severity. Our results provide insight into molecular mechanisms through which early treatment with interferons could accelerate SARS-CoV-2 clearance and mitigate against severe COVID-19.

Associations of Obesity and Neighborhood Factors With Urinary Stone Parameters.

INTRODUCTION: Obesity is associated with kidney stone disease, but it is unknown whether this association differs by SES. This study assessed the extent to which obesity and neighborhood characteristics jointly contribute to urinary risk factors for kidney stone disease. METHODS: This was a retrospective analysis of adult patients with kidney stone disease evaluated with 24-hour urine collection (2001-2020). Neighborhood-level socioeconomic data were obtained for a principal component analysis, which identified 3 linearly independent factors. Associations between these factors and 24-hour urine measurements were assessed using linear regression as well as groupings of 24-hour urine results using multivariable logistic regression. Finally, multiplicative interactions were assessed testing effect modification by obesity, and analyses stratified by obesity were performed. Analyses were performed in 2021. RESULTS: In total, 1,264 patients met the study criteria. Factors retained on principal component analysis represented SES, family structure, and housing characteristics. On linear regression, there was a significant inverse correlation between SES and 24-hour urine sodium (p=0.0002). On multivariable logistic regression, obesity was associated with increased odds of multiple stone risk factors (OR=1.61; 95% CI=1.15, 2.26) and multiple dietary factors (OR=1.33; 95% CI=1.06, 1.67). No significant and consistent multiplicative interactions were observed between obesity and quartiles of neighborhood SES, family structure, or housing characteristics. CONCLUSIONS: Obesity was associated with the presence of multiple stone risk factors and multiple dietary factors; however, the strength and magnitude of these associations did not vary significantly by neighborhood SES, family structure, and housing characteristics.

Tiny Habits® for Gratitude-Implications for Healthcare Education Stakeholders.

The COVID-19 pandemic has led to diminished sleep and increased stress, anxiety, and burnout for many health professionals and health professions students. One simple approach that may be effective for bolstering personal well-being is consciously cultivating gratitude. Gratitude is positively associated with physical health, psychological health, hope, sleep, and health behavior engagement; and randomized studies indicate that gratitude interventions can improve psychological well-being and sleep. The primary aim of this study was to assess the impact of practicing Tiny Habits® on self-reported gratitude, as measured by the 6-Item Gratitude Questionnaire (GQ-6). In January 2021, 154 adult participants with GQ-6 <35/42 were randomized to one of 3 groups: Tiny Habits for Gratitude (n = 50), Tiny Habits Control (n = 52), and Inactive Control (n = 52). Both Tiny Habits groups chose 3 Tiny Habits Recipes to practice daily and participated in the free, email-based 5-Day Program with automated daily check-in emails and personalized feedback from a Certified Tiny Habits Coach. The Recipes for the Tiny Habits for Gratitude group focused on cultivating gratitude, while those for the Tiny Habits Control group did not. Post-intervention, the mean change in GQ-6 scores in the Tiny Habits for Gratitude (Δ = ↑6.9 ± 5.6; n = 37/50, 74%; p< 0.001, Cohen's d = 0.85) and Tiny Habits Control (Δ = ↑5.6 ± 4.1; n = 31/52, 60%; p = 0.009, Cohen's d = 0.71) groups were greater than that of the Inactive Control group (Δ = ↑2.5 ± 4.4; N = 42/52, 81%). At 1 month, the mean change in GQ-6 scores in the Tiny Habits for Gratitude group (Δ = ↑7.0 ± 5.3; N = 28/50, 56%) was greater than that of the Inactive Control group (Δ = ↑2.9 ± 5.4; N = 39/52, 72%; p = 0.002, Cohen's d = 0.78). These findings suggest that practicing Tiny Habits Recipes and participating in the 5-Day Program can significantly increase gratitude in the short term and focusing specifically on gratitude during this process can sustain the increase in gratitude for up to 1 month. Implementation is quick, simple, and free. This has significant implications for healthcare education stakeholders.

Perioperative Mobile Telehealth Program for Post-Prostatectomy Incontinence: A Randomized Clinical Trial.

PURPOSE: Perioperative pelvic floor muscle training can hasten recovery of bladder control and reduce severity of urinary incontinence following radical prostatectomy. Nevertheless, most men undergoing prostatectomy do not receive this training. The purpose of this trial was to test the effectiveness of interactive mobile telehealth (mHealth) to deliver an evidence-based perioperative behavioral training program for post-prostatectomy incontinence. MATERIALS AND METHODS: This was a 3-site, 2-arm, randomized trial (2014-2019). Men with prostate cancer scheduled to undergo radical prostatectomy were randomized to a perioperative behavioral program (education, pelvic floor muscle training, progressive exercises, bladder control techniques) or a general prostate cancer education control condition, both delivered by mHealth for 1-4 weeks preoperatively and 8 weeks postoperatively. The primary outcome was time to continence following surgery measured by the ICIQ (International Consultation on Incontinence Questionnaire) Short-Form. Secondary outcomes measured at 6, 9 and 12 months included Urinary Incontinence Subscale of Expanded Prostate Cancer Index Composite; pad use; International Prostate Symptom Score QoL Question and Global Perception of Improvement. RESULTS: A total of 245 men (ages 42-78 years; mean=61.7) were randomized. Survival analysis using the Kaplan-Meier estimate showed no statistically significant between-group differences in time to continence. Analyses at 6 months indicated no statistically significant between-group differences in ICIQ scores (mean=7.1 vs 7.0, p=0.7) or other secondary outcomes. CONCLUSIONS: mHealth delivery of a perioperative program to reduce post-prostatectomy incontinence was not more effective than an mHealth education program. More research is needed to assess whether perioperative mHealth programs can be a helpful addition to standard prostate cancer care.

Associations between pain catastrophizing and resting-state functional brain connectivity: Ethnic/race group differences in persons with chronic knee pain.

Chronic pain is a significant public health problem, and the prevalence and societal impact continues to worsen annually. Multiple cognitive and emotional factors are known to modulate pain, including pain catastrophizing, which contributes to pain facilitation and is associated with altered resting-state functional connectivity in pain-related cortical and subcortical circuitry. Pain and catastrophizing levels are reported to be higher in non-Hispanic black (NHB) compared with non-Hispanic White (NHW) individuals. The current study, a substudy of a larger ongoing observational cohort investigation, investigated the pathways by which ethnicity/race influences the relationship between pain catastrophizing, clinical pain, and resting-state functional connectivity between anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (dlPFC), insula, and primary somatosensory cortex (S1). Participants included 136 (66 NHBs and 70 NHWs) community-dwelling adults with knee osteoarthritis. Participants completed the Coping Strategies Questionnaire-Revised Pain Catastrophizing subscale and Western Ontario and McMaster Universities Osteoarthritis Index. Magnetic resonance imaging data were obtained, and resting-state functional connectivity was analyzed. Relative to NHW, the NHB participants were younger, reported lower income, were less likely to be married, and self-reported greater clinical pain and pain catastrophizing (ps < 0.05). Ethnicity/race moderated the mediation effects of catastrophizing on the relationship between clinical pain and resting-state functional connectivity between the ACC, dlPFC, insula, and S1. These results indicate the NHB and NHW groups demonstrated different relationships between pain, catastrophizing, and functional connectivity. These results provide evidence for a potentially important role of ethnicity/race in the interrelationships among pain, catastrophizing, and resting-state functional connectivity.

Genetic regulation of OAS1 nonsense-mediated decay underlies association with risk of severe COVID-19.

Genomic regions have been associated with COVID-19 susceptibility and outcomes, including the chr12q24.13 locus encoding antiviral proteins OAS1-3. Here, we report genetic, functional, and clinical insights into genetic associations within this locus. In Europeans, the risk of hospitalized vs. non-hospitalized COVID-19 was associated with a single 19Kb-haplotype comprised of 76 OAS1 variants included in a 95% credible set within a large genomic fragment introgressed from Neandertals. The risk haplotype was also associated with impaired spontaneous but not treatment-induced SARS-CoV-2 clearance in a clinical trial with pegIFN-λ1. We demonstrate that two exonic variants, rs10774671 and rs1131454, affect splicing and nonsense-mediated decay of OAS1 . We suggest that genetically-regulated loss of OAS1 expression contributes to impaired spontaneous clearance of SARS-CoV-2 and elevated risk of hospitalization for COVID-19. Our results provide the rationale for further clinical studies using interferons to compensate for impaired spontaneous SARS-CoV-2 clearance, particularly in carriers of the OAS1 risk haplotypes.

Knee pain trajectories over 18 months in non-Hispanic Black and non-Hispanic White adults with or at risk for knee osteoarthritis.

BACKGROUND: Pain is the hallmark symptom of knee osteoarthritis (OA), and varies widely across individuals. Previous research has demonstrated both fluctuating and stable pain trajectories in knee OA using various time periods. Changes in pain assessed quarterly (i.e. 3-month intervals) in knee OA are relatively unknown. The current study aimed to investigate temporal variations in pain over a one and a half year period (18 months) based on quarterly characteristic pain assessments, and to examine differences in pain patterns by sociodemographic and baseline pain characteristics. METHODS: The sample included a prospective cohort of 188 participants (mean age 58 years; 63% female; 52% non-Hispanic Black) with or at risk for knee OA from an ongoing multisite investigation of ethnic/race group differences. Knee pain intensity was self-reported at baseline and quarterly over an18-month period. Baseline pain assessment also included frequency, duration, and total number of pain sites. Group-based trajectory modeling was used to identify distinct pain trajectories. Multinomial logistic regression was used to examine associations between sociodemographic characteristics, risk factors, and pain trajectory groups. RESULTS: Pain trajectories were relatively stable among a sample of adults with knee pain. Four distinct pain trajectories emerged in the overall sample, with the largest proportion of participants (35.1%) classified in the moderate-high pain group. There were significant relationships between age, education, income, ethnicity/race and trajectory group; with younger, less educated, lower income, and non-Hispanic Black participants had a greater representation in the highest pain trajectory group. CONCLUSIONS: Pain remained stable across a one and a half-year period in adults with or at risk for knee osteoarthritis, based on quarterly assessments. Certain sociodemographic variables (e.g. ethnicity/race, education, income, age) may contribute to an increased risk of experiencing greater pain.

A Mediation Appraisal of Catastrophizing, Pain-Related Outcomes, and Race in Adults With Knee Osteoarthritis.

The current cross-sectional study investigates whether pain catastrophizing mediates the relationship between ethnicity/race and pain, disability and physical function in individuals with knee osteoarthritis. Furthermore, this study examined mediation at 2-year follow-up. Participants included 187 community-dwelling adults with unilateral or bilateral knee pain who screened positive for knee osteoarthritis. Participants completed several self-reported pain-related measures and pain catastrophizing subscale at baseline and 2-year follow-up. Non-Hispanic Black (NHB) adults reported greater pain, disability, and poorer functional performance compared to their non-Hispanic White (NHW) counterparts (Ps < .05). NHB adults also reported greater catastrophizing compared to NHW adults. Mediation analyses revealed that catastrophizing mediated the relationship between ethnicity/race and pain outcome measures. Specifically, NHB individuals reported significantly greater pain and disability, and exhibited lower levels of physical function, compared to NHW individuals, and these differences were mediated by higher levels of catastrophizing among NHB persons. Catastrophizing was a significant predictor of pain and disability 2-years later in both ethnic/race groups. These results suggest that pain catastrophizing is an important variable to consider in efforts to reduce ethnic/race group disparities in chronic pain. The findings are discussed in light of structural/systemic factors that may contribute to greater self-reports of pain catastrophizing among NHB individuals. PERSPECTIVE: The current study examines whether pain catastrophizing mediates the relationship between ethnicity/race and OA-related pain, disability, and functional impairment at baseline and during a 2-year follow-up period in non-Hispanic Black and non-Hispanic White adults with knee pain. These results point to the need for interventions that target pain catastrophizing.

Effect of Serum Urate Lowering With Allopurinol on Blood Pressure in Young Adults: A Randomized, Controlled, Crossover Trial.

OBJECTIVE: To determine whether serum urate reduction with allopurinol lowers blood pressure (BP) in young adults and the mechanisms mediating this hypothesized effect. METHODS: We conducted a single-center, randomized, double-blind, crossover clinical trial. Adults ages 18-40 years with baseline systolic BP ≥120 and <160 mm Hg or diastolic BP ≥80 and <100 mm Hg, and serum urate ≥5.0 mg/dl for men or ≥4.0 mg/dl for women were enrolled. Main exclusion criteria included chronic kidney disease, gout, or past use of urate-lowering therapies. Participants received oral allopurinol (300 mg daily) or placebo for 1 month followed by a 2-4 week washout and then were crossed over. Study outcome measures were change in systolic BP from baseline, endothelial function estimated as flow-mediated dilation (FMD), and high-sensitivity C-reactive protein (hsCRP) levels. Adverse events were assessed. RESULTS: Ninety-nine participants were randomized, and 82 completed all visits. The mean ± SD age was 28.0 ± 7.0 years, 62.6% were men, and 40.4% were African American. In the primary intent-to-treat analysis, systolic BP did not change during the allopurinol treatment phase (mean ± SEM -1.39 ± 1.16 mm Hg) or placebo treatment phase (-1.06 ± 1.08 mm Hg). FMD increased during allopurinol treatment periods compared to placebo treatment periods (mean ± SEM 2.5 ± 0.55% versus -0.1 ± 0.42%; P < 0.001). There were no changes in hsCRP level and no serious adverse events. CONCLUSION: Our findings indicate that urate-lowering therapy with allopurinol does not lower systolic BP or hsCRP level in young adults when compared with placebo, despite improvements in FMD. These findings do not support urate lowering as a treatment for hypertension in young adults.