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PurposeWe evaluated and identified baseline factors associated with change in health related quality of life among patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome.Materials and methodsA total of 191 men and 233 women with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome (collectively referred to as urologic chronic pelvic pain syndrome) were followed for 12 months with bimonthly completion of the Short Form 12 to assess general mental and physical health related quality of life, and with biweekly assessment of condition specific health related quality of life using the Genitourinary Pain Index. A functional clustering algorithm was used to classify participants as improved, stable or worsened for each health related quality of life measure. Ordinal logistic regression was used to determine baseline factors associated with change.ResultsPhysical health related quality of life improved in 22% of the participants, mental health related quality of life improved in 25% and condition specific health related quality of life improved in 47%. Better baseline physical health related quality of life, older age and the presence of nonurological symptoms were associated with lower likelihood of improvement in physical health related quality of life. Better baseline mental health related quality of life, female sex, and greater baseline depression and stress were associated with a lower likelihood of improvement in mental health related quality of life. Better baseline condition specific health related quality of life and more severe baseline urologic chronic pelvic pain syndrome pain symptoms were associated with a lower likelihood of improvement in condition specific health related quality of life.ConclusionsWhile several nonurologic chronic pelvic pain syndrome factors influenced the trajectory of general health related quality of life over time, only condition specific baseline health related quality of life and urologic chronic pelvic pain syndrome symptoms were associated with urologic chronic pelvic pain syndrome specific health related quality of life change. Significant differences in how urologic chronic pelvic pain syndrome impacts various aspects of health related quality of life suggest a multidisciplinary approach to assessment and treatment of these patients.

BACKGROUND AND AIMS: Genes associated with longevity have been identified using both single gene and genome-wide approaches in a variety of species. The aim of this study was to identify quantitative trait loci (QTLs) that influence longevity in male and female mice from twenty-three C57BL/6J by DBA/2J (BXD) recombinant inbred (RI) strains. METHODS: Approximately 12 animals of each sex for each RI strain were maintained under standard conditions until natural death or moribundity criteria were met. RESULTS: A number of life span-relevant loci previously reported on chromosomes (Chrs) 7, 8, 10 and 11 were confirmed. In addition, 5 previously unreported QTLs for mouse life span on Chrs 1, 2, 6, 11, and X were identified as significant and 3 QTLs on Chrs 5, 8, and 16 were suggestive. CONCLUSIONS: Several QTLs were coincident in males and females although the modest correlation between male and female median lifespans and the identification of sex specific QTLs provide evidence that the genetic architecture underlying longevity in the sexes may differ substantially. The identification of multiple QTLs for longevity will provide valuable resources for both reductionist and integrationist research into mechanisms of life span determination. [ABSTRACT FROM AUTHOR]

Abstract: Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the likelihood of response to therapy, but it has not been tested in clinical trials for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). We explored this hypothesis using data from 3 previously published trials testing treatments for IC/BPS, which suggested modest benefits but did not meet a priori primary outcome statistical significance criteria. Importantly, these studies also collected symptom questionnaire data that allowed us to retrospectively identify participants with and without widespread pain. Analyzing the treatment by the degree of widespread pain revealed a difference in outcome and statistical significance level for each trial. Participants with predominately local pain (ie, limited widespread pain symptoms) responded to therapy targeting local symptoms, whereas those with widespread pain did not. Alternatively, participants with widespread pain beyond their local pelvic pain responded to more centrally acting treatments. Our results suggest that differentiating patients based on widespread vs more localized pain is a key consideration for designing future clinical trials for conditions with variable pain profiles, such as IC/BPS and potentially other pain-based syndromic disorders., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Aims: The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is undertaking a new cohort study in LURN II including cases and controls., Methods: This new cohort was enrolled to specifically study urinary urgency and urgency urinary incontinence, lower urinary tract symptoms (LUTSs) that are often difficult to treat due to a lack of understanding of their phenotypes and pathophysiologies., Results: This paper will focus on the motivation for the second iteration of LURN and highlight the new research techniques and plans for more thorough phenotyping of this population., Conclusions: This paper will outline the gaps in understanding in treating LUTSs, specifically urinary urgency., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Objectives: To develop a patient-reported outcome measure using qualitative patient-centered methods and expert opinion to quantify the impact of ureteral stricture disease and its management., Methods: Patients undergoing robotic ureteral reconstruction for ureteral stricture disease between 9/2021-4/2023 were enrolled. A novel patient-reported outcome was developed in four steps: 1) Semi-structured concept elicitation interviews to evaluate the physical, mental, and social effects of ureteral stricture disease; 2) Item generation based on themes identified in the interview transcripts, existing patient-reported outcomes on health-related QOL, and expert opinion; 3) Feedback on the generated items from a panel of external clinicians with high surgical volume for ureteral stricture disease; and 4) Cognitive interviews assessing patient comprehension and relevance., Results: We conducted 14 semi-structured concept-elicitation interviews. After qualitative analysis of these interviews, we generated a 13-item instrument: 8 items assessed symptoms, 4 items assessed QOL, and 1 item assessed patient-perceived treatment success. Expert input supported the content of the patient-reported outcome measure and guided minor adjustments. Two rounds of cognitive interviews were conducted. The first round included 6 patients, and the patient-reported outcome measure was revised according to patient feedback. The second round included 4 patients, and no additional revisions were made based on the second round., Conclusions: We utilized qualitative patient-centered methods and expert opinion to develop a patient reported outcome measure to assess outcomes in patients undergoing surgery for ureteral stricture disease., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ziho Lee reports a relationship with Intuitive Surgical Inc that includes: consulting or advisory. Ziho Lee reports a relationship with Boston Scientific Corporation that includes: consulting or advisory. Ziho Lee reports a relationship with Intuitive Surgical Inc that includes: funding grants. Ziho Lee reports a relationship with Kerecis LLC that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of Interest 1) Devin Boehm no conflict 2) Aurash Naser-Tavakolian no conflict 3) Kyle Nolla no conflict 4) Jonathan Rosenfelt no conflict 5) Emily Ji no conflict 6) James W. Griffith no conflict 7) Ziho Lee consultant for Intuitive Surgical and Boston Scientific, educational grants from Intuitive Surgical and Kerecis, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Men with lower urinary tract symptoms (LUTS) represent a heterogeneous group, and treatment decisions are often based on severity of symptoms and physical examination findings. Identification of clinically meaningful subtypes could allow for more personalized care. This study advances phenotyping efforts from the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) by adding data domains to previous phenotyping using urologic symptoms alone., Methods: Two-hundred-seventeen LUTS, demographics, medical history, and physical examination datapoints from the LURN Observational Cohort study were assessed among 519 men with at least one bothersome LUTS, using weighted Tanimoto indices, semi-supervised learning, and resampling-based consensus clustering to identify distinct clusters of participants. Differentially abundant serum proteins of 220 men were compared across identified clusters., Results: Five refined male clusters (RM1-RM5) were identified. Two clusters reported mild LUTS (RM1: n = 66; RM2: n = 84). RM1 was older than RM2 (70.3 vs. 56.1 years), had more comorbidities (functional comorbidity index 2.4 vs. 1.5) and erectile dysfunction. Two benign prostatic hyperplasia-like symptom clusters were identified (RM3: n = 64; RM4: n = 188). RM3 has the largest postvoid residual volume (275 mL); RM4 reported more urinary frequency, urgency, urinary incontinence, pain, and psychosocial symptoms. RM5 (n = 119) was characterized by urgency urinary incontinence, frequency, and significant comorbidities and psychosocial symptoms. Fifteen (RM2) to 87 (RM1) differentially abundant proteins were identified within each cluster. Minimal overlap was observed between affected proteins and pathways across clusters., Conclusions: Protein signatures across newly discovered subgroups suggest identified subtypes are biochemically distinct. Findings should be validated, but may represent populations with separate pathophysiology and therapeutic needs., Clinical Trial Registration: The LURN ClinicalTrials.gov Identifier is NCT02485808., (© 2024 The Author(s). Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Purpose: We aimed to assess health-related quality of life (HRQL) and its correlates among people living with HIV/AIDS (PLWHA) co-infected with SARS-CoV-2 in France., Methods: This cross-sectional was study conducted among PLWHA co-infected with SARS-CoV-2. HRQL was measured using the four dimensions of the PROQOL-HIV scale. Factors associated with each dimension were identified using linear regression., Results: mean (SD) scores for HRQL dimensions: 76.7 (± 21.1) for Physical Health and Symptoms (PHS), 79.2 (± 23.6) for Social Relationships (SR), 67.3 (± 27.4) for Mental and Cognitive (MC), and 83.9 (± 16.5) for Treatment Impact (TI). Employment status and COVID-19 knowledge were associated with higher PHS score, while blood transfusion-acquired HIV, CDC HIV, hospital discharge instructions, and self-reported symptoms were associated with lower PHS score. Couple status was associated with higher SR score, whereas, hospital discharge instructions, CDC HIV stage C, drug injection-acquired HIV, self-reported symptoms, and COVID-19 vulnerability perception were associated with lower SR score. Employment status and French birth were associated with higher MC score, while female sex, detectable HIV viral load, hospital discharge instructions, COVID-19 vulnerability perception, smoking, and self-reported symptoms were associated with lower MC score. French birth and homosexual/bisexual relationships-acquired HIV were associated with higher TI score, while detectable HIV viral load, psychiatric disorders, and self-reported symptoms were associated with lower TI score CONCLUSION: Among PLWHA co-infected with SARS-CoV-2, the scores of HRQL were impaired, particularly in the MC dimension. Findings underscore the multidimensional nature of HRQL, with notable variations across different dimensions. Understanding these correlates is crucial for tailored interventions aimed at improving the well-being of this population., (© 2024. The Author(s).)

Purpose: We aimed to estimate the prevalence of a wide range of lower urinary tract symptoms (LUTS) in US women, and explore associations with bother and discussion with health care providers, friends, and family., Materials and Methods: We analyzed baseline data collected from May 2022 to December 2023 in the RISE FOR HEALTH study-a large, regionally representative cohort study of adult female community members. LUTS and related bother were measured by the 10-item Symptoms of Lower Urinary Tract Dysfunction Research Network Symptom Index, and discussion was assessed by a study-specific item., Results: Of the 3000 eligible participants, 73% (95% CI 71%-74%) reported any storage symptoms, 52% (95% CI 50%-53%) any voiding or emptying symptoms, and 11% (95% CI 10%-13%) any pain with bladder filling, for an overall LUTS prevalence of 79% (95% CI 78%-81%). This prevalence estimate included 43% (95% CI 41%-45%) of participants with mild to moderate symptoms and 37% (95% CI 35%-38%) with moderate to severe symptoms. Over one-third of participants reported LUTS-related bother (38%, 95% CI 36%-39%) and discussion (38%, 95% CI 36%-40%), whereas only 7.1% (95% CI 6.2%-8.1%) reported treatment. Urgency and incontinence (including urgency and stress incontinence) were associated with the greatest likelihood of bother and/or discussion (adjusted prevalence ratios = 1.3-2.3), even at mild to moderate levels. They were also the most commonly treated LUTS., Conclusions: LUTS, particularly storage LUTS such as urgency and incontinence, were common and bothersome in the RISE study population, yet often untreated. Given this large burden, both prevention and treatment-related interventions are warranted to reduce the high prevalence and bother of LUTS.

Importance: Chronic skin disorders in children frequently are visible and can cause stigmatization. However, the extent of stigmatization from chronic skin disease and association with mental health needs further study., Objective: To examine the extent of stigma, dependence on disease visibility and severity, and association with mental health and quality of life (QOL) in chronic pediatric skin disease., Design, Setting, and Participants: A cross-sectional, single-visit study was conducted at 32 pediatric dermatology centers in the US and Canada from November 14, 2018, to November 17, 2021. Participants included patients aged 8 to 17 years with chronic skin disease and 1 parent., Main Outcomes and Measures: Using the Patient-Reported Outcomes Measurement Instrumentation System (PROMIS) Stigma-Skin, the extent of stigma with child-, caregiver-, and physician-assessed disease visibility (primary outcome) and severity was compared, as well as reduced QOL (assessed by Skindex-Teen), depression, anxiety, and poor peer relationships (PROMIS child and proxy tools) (secondary outcomes)., Results: The study included 1671 children (57.9% female; mean [SD] age, 13.7 [2.7] years). A total of 56.4% participants had self-reported high disease visibility and 50.5% had moderate disease severity. Stigma scores significantly differed by level of physician-assessed and child/proxy-assessed disease visibility and severity. Among children with chronic skin disorders, predominantly acne, atopic dermatitis, alopecia areata, and vitiligo, only 27.0% had T scores less than 40 (minimal or no stigma) and 43.8% had at least moderate stigma (T score ≥45) compared with children with a range of chronic diseases. Stigma scores correlated strongly with reduced QOL (Spearman ρ = 0.73), depression (ρ = 0.61), anxiety (ρ = 0.54), and poor peer relationships (ρ = -0.49). Overall, 29.4% of parents were aware of bullying of their child, which was strongly associated with stigma (Cohen d = -0.79, with children who were not bullied experiencing lower levels of stigma). Girls reported more stigma than boys (Cohen d = 0.26). Children with hyperhidrosis and hidradenitis suppurativa were most likely to have increased depression and anxiety., Conclusions and Relevance: The findings of this study suggest that physician assessment of disease severity and visibility is insufficient to evaluate the disease impact in the patient/caregiver. Identifying stigmatization, including bullying, and tracking improvement through medical and psychosocial interventions may be a key role for practitioners.

Background: Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) significantly impact quality of life among older men. Despite the prevalent use of the American Urological Association Symptom Index (AUA-SI) for BPH, this measure overlooks key symptoms such as pain and incontinence, underscoring the need for more comprehensive patient-reported outcome (PRO) tools. This study aims to integrate enhanced PROs into routine clinical practice to better capture the spectrum of LUTS, thereby improving clinical outcomes and patient care., Methods: This prospective observational study will recruit men with LUTS secondary to BPH aged ≥ 50 years from urology clinics. Participants will be stratified into medical and surgical management groups, with PRO assessments scheduled at regular intervals to monitor LUTS and other health outcomes. The study will employ the LURN Symptom Index (SI)-29 alongside the traditional AUA-SI and other non-urologic PROs to evaluate a broad range of symptoms. Data on comorbidities, symptom severity, and treatment efficacy will be collected through a combination of electronic health records and PROs. Analyses will focus on the predictive power of these tools in relation to symptom trajectories and treatment responses. Aims are to: (1) integrate routine clinical tests with PRO assessment to enhance screening, diagnosis, and management of patients with BPH; (2) examine psychometric properties of the LURN SIs, including test-retest reliability and establishment of clinically meaningful differences; and (3) create care-coordination recommendations to facilitate management of persistent symptoms and common comorbidities measured by PROs., Discussion: By employing comprehensive PRO measures, this study expects to refine symptom assessment and enhance treatment monitoring, potentially leading to improved personalized care strategies. The integration of these tools into clinical settings could revolutionize the management of LUTS/BPH by providing more nuanced insights into patient experiences and outcomes. The findings could have significant implications for clinical practices, potentially leading to updates in clinical guidelines and better health management strategies for men with LUTS/BPH., Trial Registration: This study is registered in ClinicalTrials.gov (NCT05898932)., (© 2024. The Author(s).)

Purpose: This study tested the hypothesis that ecological momentary assessment (EMA) of pelvic pain (PP) and urinary urgency (UU) would reveal unique Urologic Chronic Pelvic Pain Syndrome (UCPPS) phenotypes that would be associated with disease specific quality of life (QOL) and illness impact metrics (IIM)., Materials and Methods: A previously validated smart phone app (M-app) was provided to willing Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) participants. M-app notifications were sent 4-times daily for 14 days inquiring about PP and UU severity. A clustering algorithm that accounted for variance placed participants into PP and UU variability? clusters. Associations between clusters and QOL and IIM were then determined., Results: A total of 204 participants enrolled in the M-app study (64% female). M-app compliance was high (median 63% of surveys). Cluster analysis revealed k = 3 (high, low, none) PP clusters and k = 2 (high, low) UU clusters. When adjusting for baseline pain severity, high PP variability, but not UU variability, was strongly associated with QOL and IIM; specifically worse mood, worse sleep and higher anxiety. UU and PP clusters were associated with each other (p < 0.0001), but a large percentage (33%) of patients with high PP variability had low UU variability., Conclusions: PP variability is an independent predictor of worse QOL and more severe IIM in UCPPS participants after controlling for baseline pain severity and UU. These findings suggest alternative pain indices, such as pain variability and unpredictability, may be useful adjuncts to traditional measures of worst and average pain when assessing UCPPS treatment responses., (© 2024 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Importance: Physical health and psychological health represent modifiable factors in the causal pathway of lower urinary tract symptoms (LUTS)., Objectives: Understand the relationship between physical and psychological factors and LUTS over time., Study Design: Adult women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network observational cohort study completed the LUTS Tool and Pelvic Floor Distress Inventory, including urinary (Urinary Distress Inventory), prolapse (Pelvic Organ Prolapse Distress Inventory), and colorectal anal (Colorectal-Anal Distress Inventory) subscales at baseline, 3 months, and 12 months. Physical functioning, depression, and sleep disturbance were measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires; relationships were assessed using multivariable linear mixed models., Results: Of 545 women enrolled, 472 had follow-up. Median age was 57 years; 61% and 78% reported stress urinary incontinence and overactive bladder, respectively; and 81% reported obstructive symptoms. The PROMIS depression scores were positively associated with all urinary outcomes (range, 2.5- to 4.8-unit increase per 10-unit increase in depression score; P < 0.01 for all). Higher sleep disturbance scores were associated with higher urgency, obstruction, LUTS Total Severity, Urinary Distress Inventory, and Pelvic Floor Distress Inventory (1.9- to 3.4-point increase per 10-unit increase, all P < 0.02). Better physical functioning was associated with less severe urinary symptoms except stress urinary incontinence (2.3- to 5.2-point decrease per 10-unit increase, all P < 0.01). All symptoms decreased over time; however, no association was detected between baseline PROMIS scores and trajectories of LUTS over time., Conclusions: Nonurologic factors demonstrated small to medium cross-sectional associations with urinary symptom domains, but no significant association was detected with changes in LUTS. Further work is needed to determine whether interventions targeting nonurologic factors reduce LUTS in women., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2023 American Urogynecologic Society. All rights reserved.)

Respiratory viral infections are frequent causes of acute respiratory distress syndrome (ARDS), a disabling condition with a mortality of up to 46%. The pulmonary endothelium plays an important role in the development of ARDS as well as the pathogenesis of pulmonary fibrosis; however, the therapeutic potential to modulate endothelium-dependent signaling to prevent deleterious consequences has not been well explored. Here, we used a clinically relevant influenza A virus infection model, endothelial cell-specific transgenic gain-of-function and loss-of-function mice as well as pharmacologic approaches and in vitro modeling, to define the mechanism by which S1PR1 expression is dampened during influenza virus infection and determine whether therapeutic augmentation of S1PR1 has the potential to reduce long-term postviral fibrotic complications. We found that the influenza virus-induced inflammatory milieu promoted internalization of S1PR1, which was pharmacologically inhibited with paroxetine, an inhibitor of GRK2. Moreover, genetic overexpression or administration of paroxetine days after influenza virus infection was sufficient to reduce postviral pulmonary fibrosis. Taken together, our data suggest that endothelial S1PR1 signaling provides critical protection against long-term fibrotic complications after pulmonary viral infection. These findings support the development of antifibrotic strategies that augment S1PR1 expression in virus-induced ARDS to improve long-term patient outcomes.

We sought to analyze the relationship between health literacy, confidence in COVID-19 vaccines, and self-reported vaccination. We hypothesized that the relationship between health literacy and vaccination would be mediated by vaccine confidence. We recruited (N = 271) English- and Spanish-speaking adults in Boston and Chicago from September 2018 to September 2021. We performed a probit mediation analysis to determine if confidence in COVID-19 vaccines and health literacy predicted self-reported vaccination. We hypothesized that the relationship between health literacy and vaccination would be mediated by vaccine confidence. Participants were on average 50 years old, 65% female, 40% non-Hispanic Black, 25% Hispanic, and 30% non-Hispanic White; 231 (85%) reported at least one COVID-19 vaccination. A higher mean vaccine confidence score ( t = -7.9, p < 0.001) and higher health literacy ( t = -2.2, p = 0.03) were associated with vaccination, but only vaccine confidence predicted vaccination in a multivariate model. Vaccine confidence mediated the relationship between health literacy and COVID-19 vaccination (mediated effects: 0.04; 95% CI [0.02, 0.08]). We found that using a simple tool to measure vaccine confidence identified people who declined or delayed COVID-19 vaccination in a diverse sample of adults with varying levels of health literacy. Simple short survey tools can be useful to identify people who may benefit from vaccine promotion efforts and evidence-based communication strategies.

Regulatory T (T reg ) cell modulation of adaptive immunity and tissue homeostasis is well described; however, less is known about T reg cell-mediated regulation of the innate immune response. Here we show that deletion of ST2, the receptor for interleukin (IL)-33, on T reg cells increased granulocyte influx into the lung and increased cytokine production by innate lymphoid and γδ T cells without alteration of adaptive immunity to influenza. IL-33 induced high levels of the interleukin-1 receptor antagonist (IL-1Ra) in ST2 + T reg cells and deletion of IL-1Ra in T reg cells increased granulocyte influx into the lung. T reg cell-specific deletion of ST2 or IL-1Ra improved survival to influenza, which was dependent on IL-1. Adventitial fibroblasts in the lung expressed high levels of the IL-1 receptor and their chemokine production was suppressed by T reg cell-produced IL-1Ra. Thus, we define a new pathway where IL-33-induced IL-1Ra production by tissue T reg cells suppresses IL-1-mediated innate immune responses to respiratory viral infection., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Alzheimer's disease and related dementias (ADRD) are among the most feared age-related conditions. The aim of this study was to evaluate a brief psychological intervention to promote adaptive coping in older adults experiencing heightened fear of ADRD and investigate positive downstream effects on health-related secondary outcomes, including frequency of reported memory failures, psychosocial functioning, and quality of life., Methods: Eighty-one older adults were recruited and randomized into REFRAME or active control intervention arms. Both groups received psycho-education and training in mindful monitoring of fears related to ADRD. The REFRAME group received an additional behavioral activation component intended to disrupt maladaptive avoidant coping (i.e., avoidance) strategies. Both groups completed 3-weeks of intervention exercises with accompanying questionnaires (baseline, mid- and post-intervention and 4-week follow-up)., Results: Adherence was strong (> 75%). We observed a significant reduction in ADRD-related fear and avoidance in both groups. Significant reductions were also observed for frequency of self-reported memory failures, anxiety, and depression. Depression was significantly reduced in the REFRAME group compared to the control group. Significant increases in participants' ability to participate in social activities and well-being were also observed., Conclusions: Findings suggest that a brief psychological intervention can mitigate ADRD-related fears and avoidant coping in older adults, and that benefits extend to broader health-related outcomes including anxiety, depression, social functioning, and well-being. Addressing ADRD-related fear has implications for healthy aging and risk reduction, as individuals may be more likely to engage in activities that are protective against ADRD but were previously avoided., Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04821960 ., (© 2023. The Author(s).)

Abstract: Urologic chronic pelvic pain syndrome (UCPPS) is a complex, debilitating condition in which patients often report nonpelvic pain in addition to localized pelvic pain. Understanding differential predictors of pelvic pain only vs widespread pain may provide novel pathways for intervention. This study leveraged baseline data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network's Symptom Pattern Study to investigate the impact of childhood sexual and nonsexual violent trauma on pelvic and nonpelvic pain sensitivity among adult patients with UCPPS, as well as potential mediators of this association. Study participants who met inclusion criteria for UCPPS completed questionnaires assessing childhood and recent trauma, affective distress, cognitive dysfunction, and generalized sensory sensitivity. Experimental pain sensitivity was also evaluated using standardized pressure pain applied to the pubic region and the arm. Bivariate analyses showed that childhood violent trauma was associated with more nonviolent childhood trauma, more recent trauma, poorer adult functioning, and greater pain sensitivity at the pubic region, but not pain sensitivity at the arm. Path analysis suggested that childhood violent trauma was indirectly associated with pain sensitivity at both sites and that this indirect association was primarily mediated by generalized sensory sensitivity. More experiences of recent trauma also contributed to these indirect effects. The findings suggest that, among participants with UCPPS, childhood violent trauma may be associated with heightened pain sensitivity to the extent that trauma history is associated with a subsequent increase in generalized sensory sensitivity., (Copyright © 2023 International Association for the Study of Pain.)

Objectives: We investigated how individuals with chronic obstructive pulmonary disease (COPD) and multi-morbidity (MM) navigate barriers and facilitators to their health management., Methods: We conducted a mixed-methods study using semi-structured interviews and survey assessments of adults with COPD, hypertension, and/or diabetes. We recruited 18 participants with an average age of 65, with 39% being male, 50% Black, and 22% Hispanic/Latino/a. Five investigators used an iterative, hybrid-coding process combining a priori and emergent codes to analyze transcripts and compare quantitative and qualitative data for themes., Results: Participants reported a generalized approach to their health rather than managing MMs separately. Individuals with good or mixed adherence found daily routines facilitated regular medication use, while those with poor adherence experienced complex prescriptions and life stressors as barriers. Walking was viewed as beneficial but challenging due to limited mobility. Most participants viewed diet as important to their MMs, but only two reported high diet quality and many held inaccurate beliefs about healthy diet choices., Discussion: Participants with MM were highly motivated to engage in self-management activities, but some individuals experienced barriers to maintaining them. Emphasizing an individualized clinical approach to assessing and solving patient barriers may improve self-management outcomes in this complex population.

Purpose: Symptom heterogeneity in interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively termed urological chronic pelvic pain syndrome, has resulted in difficulty in defining appropriate clinical trial endpoints. We determine clinically important differences for 2 primary symptom measures, pelvic pain severity and urinary symptom severity, and evaluate subgroup differences., Materials and Methods: The Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study enrolled individuals with urological chronic pelvic pain syndrome. We defined clinically important differences by associating changes in pelvic pain severity and urinary symptom severity over 3 to 6 months with marked improvement on a global response assessment using regression and receiver operating characteristic curves. We evaluated clinically important differences for absolute and percent change and examined differences in clinically important differences by sex-diagnosis, presence of Hunner lesions, pain type, pain widespreadness, and baseline symptom severity., Results: An absolute change of -4 was clinically important in pelvic pain severity among all patients, but clinically important difference estimates differed by pain type, presence of Hunner lesions, and baseline severity. Pelvic pain severity clinically important difference estimates for percent change were more consistent across subgroups and ranged from 30% to 57%. The absolute change urinary symptom severity clinically important difference was -3 for female participants and -2 for male participants with chronic prostatitis/chronic pelvic pain syndrome only. Patients with greater baseline severity required larger decreases in symptoms to feel improved. Estimated clinically important differences had lower accuracy among participants with low baseline symptoms., Conclusions: A reduction of 30%-50% in pelvic pain severity is a clinically meaningful endpoint for future therapeutic trials in urological chronic pelvic pain syndrome. Urinary symptom severity clinically important differences are more appropriately defined separately for male and female participants.

Introduction: The spectrum of bladder health and the factors that promote bladder health and prevent lower urinary tract symptoms (LUTS) among women are not well understood. This manuscript describes the rationale, aims, study design, sampling strategy, and data collection for the RISE FOR HEALTH (RISE) study, a novel study of bladder health in women conducted by the Prevention of Lower Urinary Tract Symptom (PLUS) Research Consortium., Methods and Results: RISE is a population-based, multicenter, prospective longitudinal cohort study of community-dwelling, English- and Spanish-speaking adult women based in the United States. Its goal is to inform the distribution of bladder health and the individual factors (biologic, behavioral, and psychosocial) and multilevel factors (interpersonal, institutional, community, and societal) that promote bladder health and/or prevent LUTS in women across the life course. Key study development activities included the: (1) development of a conceptual framework and philosophy to guide subsequent activities, (2) creation of a study design and sampling strategy, prioritizing diversity, equity, and inclusion, and (3) selection and development of data collection components. Community members and cross-cultural experts shaped and ensured the appropriateness of all study procedures and materials. RISE participants will be selected by simple random sampling of individuals identified by a marketing database who reside in the 50 counties surrounding nine PLUS clinical research centers. Participants will complete self-administered surveys at baseline (mailed paper or electronic) to capture bladder health and LUTS, knowledge about bladder health, and factors hypothesized to promote bladder health and prevent LUTS. A subset of participants will complete an in-person assessment to augment data with objective measures including urogenital microbiome specimens. Initial longitudinal follow-up is planned at 1 year., Discussion: Findings from RISE will begin to build the necessary evidence base to support much-needed, new bladder health promotion and LUTS prevention interventions in women., (© 2022 Wiley Periodicals LLC.)

Introduction: Alzheimer's disease and related dementias (ADRD) are among the most feared conditions. However, research around ADRD-specific fear and avoidance behaviors is lacking. Here, we validated a novel measure of fear and avoidance specific to memory loss, the Fear and Avoidance of Memory Loss (FAM) scale, and examined associations between fear avoidance and psychosocial functioning in older adults., Methods: We assessed FAM Scale internal reliability and concurrent validity, and candidate subscales across two samples (total N  = 813). We then examined associations between fear avoidance and memory performance, anxiety, depressive symptoms, sleep, social functioning, and quality of life., Results: We identified two subscales: fear and avoidance, which yielded strong psychometric validity. Higher fear was associated with memory failures and sleep disturbance. Higher avoidance was associated with memory failures, poorer verbal memory, reduced social functioning, and quality of life., Discussion: We present the first measure of fear avoidance specific to memory loss. We propose that targeting fear avoidance can promote ADRD risk reduction and resiliency., Competing Interests: The authors declare no conflicts. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Background: A high rate of COVID-19 vaccination is critical to reduce morbidity and mortality related to infection and to control the COVID-19 pandemic. Understanding the factors that influence vaccine confidence can inform policies and programs aimed at vaccine promotion. We examined the impact of health literacy on COVID-19 vaccine confidence among a diverse sample of adults living in two major metropolitan areas., Methods: Questionnaire data from adults participating in an observational study conducted in Boston and Chicago from September 2018 through March 2021 were examined using path analyses to determine whether health literacy mediates the relationship between demographic variables and vaccine confidence, as measured by an adapted Vaccine Confidence Index (aVCI)., Results: Participants (N = 273) were on average 49 years old, 63 % female, 4 % non-Hispanic Asian, 25 % Hispanic, 30 % non-Hispanic white, and 40 % non-Hispanic Black. Using non-Hispanic white and other race as the reference category, Black race and Hispanic ethnicity were associated with lower aVCI (-0.76, 95 % CI -1.00 to -0.50; -0.52, 95 % CI -0.80 to -0.27, total effects from a model excluding other covariates). Lower education was also associated with lower aVCI (using college or more as the reference, -0.73 for 12th grade or less, 95 % CI -0.93 to -0.47; -0.73 for some college/associate's/technical degree, 95 % CI -1.05 to -0.39). Health literacy partially mediated these effects for Black and Hispanic participants and those with lower education (indirect effects -0.19 and -0.19 for Black race and Hispanic ethnicity; 0.27 for 12th grade or less; -0.15 for some college/associate's/technical degree)., Conclusions: Lower levels of education, Black race, and Hispanic ethnicity were associated with lower scores on health literacy, which in turn were associated with lower vaccine confidence. Our findings suggest that efforts to improve health literacy may improve vaccine confidence, which in turn may improve vaccination rates and vaccine equity., Clinical Trials Number: NCT03584490., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JWG declares that he and his lab have received a research grant from Pfizer to create a patient decision aid for children with atopic dermatitis (unrelated to this manuscript and unrelated to vaccines, vaccine confidence, and COVID-19); Pfizer is a maker of one common COVID-19 vaccine (Pfizer-BioNTech). He and his lab also have funding for research from the National Institutes of Health and the National Eczema Association. He has no other interests to declare. MPO is a primary investigator on multiple National Institute of Health funded research projects. Otherwise, the authors whose names are listed immediately certify that they have no other affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Most health literacy measures require in-person administration or rely upon self-report., Objective: We sought to develop and test the feasibility of a brief, objective health literacy measure that could be deployed via text messaging or online survey., Design: Participants were recruited from ongoing NIH studies to complete a phone interview and online survey to test candidate items. Psychometric analyses included parallel analysis for dimensionality and item response theory. After 9 months, participants were randomized to receive the final instrument via text messaging or online survey., Participants: Three hundred six English and Spanish-speaking adults with ≥ 1 chronic condition MAIN MEASURES: Thirty-three candidate items for the new measure and patient-reported physical function, anxiety, depression, and medication adherence. All participants previously completed the Newest Vital Sign (NVS) in parent NIH studies., Key Results: Participants were older (average 67 years), 69.6% were female, 44.3% were low income, and 22.0% had a high school level of education or less. Candidate items loaded onto a single factor (RMSEA: 0.04, CFI: 0.99, TLI: 0.98, all loadings >.59). Six items were chosen for the final measure, named the HL6. Items demonstrated acceptable internal consistency (α=0.73) and did not display differential item functioning by language. Higher HL6 scores were significantly associated with greater educational attainment (r=0.41), higher NVS scores (r=0.55), greater physical functioning (r=0.26), fewer depressive symptoms (r=-0.20), fewer anxiety symptoms (r=-0.15), and fewer barriers to medication adherence (r=-0.30; all p<.01). In feasibility testing, 75.2% of participants in the text messaging arm completed the HL6 versus 66.2% in the online survey arm (p=0.09). Socioeconomic disparities in completion were more common in the online survey arm., Conclusions: The HL6 demonstrates adequate reliability and validity in both English and Spanish. This performance-based assessment can be administered remotely using commonly available technologies with fewer logistical challenges than assessments requiring in-person administration., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: Most children with atopic dermatitis (AD) experience sleep disturbance, but reliable and valid assessment tools are lacking., Objectives: To test the Patient-Reported Outcomes Measurement Information System (PROMIS) sleep measures in pediatric AD and to develop an algorithm to screen, assess, and intervene to reduce sleep disturbance., Methods: A cross-sectional study was conducted with children with AD ages 5 to 17 years and 1 parent (n = 61), who completed sleep, itch, and AD-specific questionnaires; clinicians assessed disease severity. All children wore actigraphy watches for a 1-week objective sleep assessment., Results: PROMIS sleep disturbance parent proxy reliability was high (Cronbach α = 0.90) and was differentiated among Patient-Oriented Eczema Measure (POEM)-determined disease severity groups (mean ± standard deviation in mild vs moderate vs severe was 55.7 ± 7.5 vs 59.8 ± 10.8 vs 67.1 ± 9.5; P < .01). Sleep disturbance correlated with itch (numeric rating scale, r = 0.48), PROMIS sleep-related impairment (r = 0.57), and worsened quality of life (Children's Dermatology Life Quality Index, r = 0.58), with all P values less than .01. Positive report on the POEM sleep disturbance question has high sensitivity (95%) for PROMIS parent proxy-reported sleep disturbance (T-score ≥ 60). An algorithm for screening and intervening on sleep disturbance was proposed., Limitations: This was a local sample., Conclusions: Sleep disturbance in pediatric AD should be screened using the POEM sleep question, with further assessment using the PROMIS sleep disturbance measure or objective sleep monitoring if needed., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Limited epidemiological data exist describing how patients engage with various treatments for overactive bladder (OAB). To improve care for patients with OAB, it is essential to gain a better understanding of how patients interface with OAB treatments longitudinally, that is, how often patients change treatments and the pattern of this treatment change in terms of escalation and de-escalation., Objectives: To describe treatment patterns for women with bothersome urinary urgency (UU) and/or urgency urinary incontinence (UUI) presenting to specialty care over 1 year., Study Design: The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) study enrolled adult women with bothersome UU and/or UUI seeking care for lower urinary tract symptoms (LUTS) between January 2015 and September 2016. An ordinal logistic regression model was fitted to describe the probabilities of escalating or de-escalating level of treatment during 1-year follow-up., Results: Among 349 women, 281 reported UUI and 68 reported UU at baseline. At the end of 1 year of treatment by a urologist or urogynecologist, the highest level of treatment received by participants was 5% expectant management, 36% behavioral treatments (BT), 26% physical therapy (PT), 26% OAB medications, 1% percutaneous tibial nerve stimulation, 3% intradetrusor onabotulinum toxin A injection, and 3% sacral neuromodulation. Participants using BT or PT at baseline were more likely to be de-escalated to no treatment than participants on OAB medications at baseline, who tended to stay on medications. Predictors of the highest level of treatment included starting level of treatment, hypertension, UUI severity, stress urinary incontinence, and anticholinergic burden score., Conclusions: Treatment patterns for UU and UUI are diverse. Even for patients with significant bother from OAB presenting to specialty clinics, further treatment often only involves conservative or medical therapies. This study highlights the need for improved treatment algorithms to escalate patients with persistent symptoms, or to adjust care in those who have been unsuccessfully treated., (© 2022 Wiley Periodicals LLC.)

Objective: To determine how the LURN-SI-10, a novel questionnaire developed by the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), compares with the International Prostate Symptom Score (IPSS) in men with lower urinary tract symptoms (LUTS) attributed to benign prostatic hyperplasia (BPH). Specifically, to assess convergent validity and determine how frequently the LURN-SI-10 identifies symptoms not captured by the IPSS., Materials and Methods: Men presenting with BPH/LUTS were prospectively administered LURN-SI-10 and IPSS questionnaires. Urinary incontinence (UI) including post-void dribbling (PVD), urgency urinary incontinence (UUI), stress urinary incontinence (SUI), as well as bladder pain were considered present if the patient reported "about half the time or more" on LURN-SI-10. Correlations between LURN-SI-10 and IPSS were assessed as continuous and categorical variables. Multivariable linear regression analysis was performed to determine associations with symptom scores., Results: LURN-SI-10 and IPSS were highly correlated in men with BPH/LUTS (r = 0.82, n = 429), as were respective bother and quality of life scores (ρ = 0.74). The LURN-SI-10 identified additional symptoms including PVD (24%), UUI (13%), SUI (2%), and pain (8%). Men with any UUI, SUI, or PVD had on average a 7.6-point higher LURN-SI-10 score than those without UI (P<.001) and 8.0-point higher IPSS score than those without UI (P<.001)., Conclusion: The LURN-SI-10 correlates strongly with the IPSS, but the LURN-SI-10 identifies additional important symptomatology in men with LUTS. This additional information may improve the evaluation and treatment of men with BPH/LUTS. Further prospective studies of the LURN-SI-10 is warranted., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Atopic dermatitis is a pruritic chronic condition associated with significant sleep disturbance, inattention, and sometimes behavioral problems. Enhancing resiliency in children with atopic dermatitis may promote coping strategies to improve quality of life. Positive psychology is one strategy that can be used to strengthen resiliency., Objective: Our objective was to identify positive psychology concepts mentioned by children with atopic dermatitis and their parent to inform strategies to strengthen resiliency in children with atopic dermatitis., Methods: A total of 20 patient-parent dyads were interviewed to share their experience with atopic dermatitis to help develop a novel psychologic intervention for atopic dermatitis. Patients were 8 to 17 years old and diagnosed with atopic dermatitis. Trained coders analyzed transcripts using a coding dictionary developed based on Seligman's PERMA (positive emotion, engagement, relationships, meaning, and accomplishment) model of positive psychology. The frequency of unprompted mentions of PERMA themes and relevant quotations was captured. Transcripts were also separately coded for resiliency, which is the ultimate goal of PERMA., Results: Positive psychology concepts were mentioned by 100% (20/20) of children and 95% (19/20) of parents. Engagement and relationships, both negative and positive aspects, were the most common unprompted PERMA themes mentioned by children (14/20, 70%) and parents (13/20, 65%). Emotion elicited the most negative comments from children (19/20, 95%) and parents (17/20, 85%). When analyzed for resiliency, 8 participants were identified with at least one resiliency code. On average, participants with a resiliency code mentioned PERMA concepts 9.1 (SD 4.7) times compared to those who mentioned none (mean 5.9, SD 4.6) (P=.14). When participants were stratified by disease severity, on average, more positive psychology concepts were mentioned by patients with mild atopic dermatitis (mean 13, SD 3.0) than those with moderate symptoms (mean 6.2, SD 4.9) or severe symptoms (mean 6.1, SD 4.0) (P=.03)., Conclusions: Among PERMA themes, engagement and relationships are the two most commonly mentioned categories for children with atopic dermatitis. Strategies targeting PERMA such as affirmations and positive reframing may improve psychosocial well-being and resiliency in pediatric atopic dermatitis. Future directions will look at incorporating "positive medicine" into atopic dermatitis treatment to not only relieve symptoms but also strengthen positive aspects of life., (©Terry M Lou, Kenneth L Zhang, Noël C Slesinger, Michelle Taddeo, Eloisa Serrano, Wendy Smith Begolka, Korey Capozza, Amy S Paller, James W Griffith, Anna B Fishbein. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org), 14.09.2022.)

Three categories of pain mechanisms are recognized as contributing to pain perception: nociceptive, neuropathic, and nociplastic (ie, central nervous system augmented pain processing). We use validated questionnaires to identify pain mechanisms in Urologic Chronic Pelvic Pain Syndrome (UCCPS) patients (n = 568, female = 378, male = 190) taking part in the Symptom Patterns Study of the Multidisciplinary Approach to the study of chronic Pelvic Pain Research Network. A cutoff score of 12 on the painDETECT questionnaire (-1 to 38) was used to classify patients into the neuropathic category while the median score of 7 on the fibromyalgia survey criteria (0-31) was used to classify patients into the nociplastic category. Categories were compared on demographic, clinical, psychosocial, psychophysical and medication variables. At baseline, 43% of UCPPS patients were classified as nociceptive-only, 8% as neuropathic only, 27% as nociceptive+nociplastic, and 22% as neuropathic+nociplastic. Across outcomes nociceptive-only patients had the least severe symptoms and neuropathic+nociplastic patients the most severe. Neuropathic pain was associated with genital pain and/or sensitivity on pelvic exam, while nociplastic pain was associated with comorbid pain conditions, psychosocial difficulties, and increased pressure pain sensitivity outside the pelvis. A self-report method classifying individuals on pain mechanisms reveals clinical differences that could inform clinical trials and novel targets for treatment. PERSPECTIVE: This article presents differences in clinical characteristics based on a simple self-report method of classifying pain mechanisms for Urologic Chronic Pelvic Pain Syndrome patients. This method can be easily applied to other chronic pain conditions and may be useful for exploring pathophysiology in pain subtypes., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: The impact of nonurological factors on male lower urinary tract symptoms (LUTS) remains unclear. We investigated cross-sectional and longitudinal associations among anxiety, depression, physical function, sleep quality and urinary symptom subdomains., Materials and Methods: Data from 518 men in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) study were analyzed to identify associations between Patient-Reported Outcomes Measurement Information System® (PROMIS®) depression, anxiety, sleep disturbance and physical function measures and LUTS subdomains, as derived from the American Urological Association Symptom Index and LUTS Tool. Multivariable linear regression was used to assess the relationships between PROMIS measures and LUTS subdomains at baseline and at 3- and 12-month followup., Results: Baseline depression and anxiety were associated with urinary incontinence (p <0.001), voiding symptoms (p <0.001) and quality of life (p=0.002), whereas baseline sleep disturbance was associated with voiding and storage symptoms and quality of life (p <0.001 for all). Urinary symptom severity improved in all subdomains at 3 and 12 months. Similar associations between PROMIS measures and LUTS subdomains were observed at all time points, but baseline depression, anxiety, sleep disturbance and physical function measures were not associated with longitudinal trajectories of LUTS., Conclusions: Urinary symptom subdomains are independently associated with modifiable clinical variables including sleep quality and depression at all time points, but these variables do not predict the degree of improvement in LUTS following urological evaluation and treatment over the medium term. Bidirectional assessment and randomized experiments may improve our understanding of these relationships.

We present a methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center observational study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data types (continuous and categorical) required novel methodology using a weighted Tanimoto indices approach. Data domains only available on a subset of the cohort were integrated using a semi-supervised clustering approach. Novel contrast criterion for determination of the optimal number of clusters in consensus clustering was introduced and compared with existing criteria. Distinctiveness of the clusters was confirmed by using multiple criteria for cluster quality, and by testing for significantly different variables in pairwise comparisons of the clusters. Cluster dynamics were explored by analyzing longitudinal data at 3- and 12-month follow-up. Five clusters of women with LUTS were identified using the developed methodology. None of the clusters could be characterized by a single symptom, but rather by a distinct combination of symptoms with various levels of severity. Targeted proteomics of serum samples demonstrated that differentially abundant proteins and affected pathways are different across the clusters. The clinical relevance of the identified clusters is discussed and compared with the current conventional approaches to the evaluation of LUTS patients. The rationale and thought process are described for the selection of procedures for data preprocessing, clustering, and cluster evaluation. Suggestions are provided for minimum reporting requirements in publications utilizing clustering methodology with multiple heterogeneous data domains., Competing Interests: The authors have declared that no competing interests exist.

Purpose: We assessed the reliability and validity of an efficient severity assessment for pelvic pain and urinary symptoms in urological chronic pelvic pain syndrome, which consists of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome., Materials and Methods: A total of 578 patients were assessed using brief, empirically derived self-report scales for pelvic pain severity (PPS) and urinary symptom severity (USS) 4 times during a 1-month period and baseline clinic visit that included urological, pain and illness-impact measures. Mild, moderate and severe categories on each dimension were examined for measurement stability and construct validity., Results: PPS and USS severity categories had adequate reliability and both discriminant validity (differential relationships with specific clinical and self-report measures) and convergent validity (common association with nonurological somatic symptoms). For example, increasing PPS was associated with pelvic tenderness and widespread pelvic pain, whereas USS was associated with urgency during a bladder filling test and increased sensory sensitivity. PPS and USS categories were independently associated with nonurological pain and emotional distress. A descriptive analysis identified higher likelihood characteristics associated with having moderate to severe PPS or USS or both. Lack of sex interactions indicated that the measures are comparable in interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome., Conclusions: Women and men with urological chronic pelvic pain syndrome can be reliably subgrouped using brief self-report measures of mild, moderate or severe pelvic pain and urinary symptoms. Comparisons with a broad range of clinical variables demonstrate the validity and potential clinical utility of these classifications, including use in clinical trials, health services and biological research.

Abstract: The objective of this study is to validate a placebo pill response predictive model-a biosignature-that classifies chronic pain patients into placebo responders (predicted-PTxResp) and nonresponders (predicted-PTxNonR) and test whether it can dissociate placebo and active treatment responses. The model, based on psychological and brain functional connectivity, was derived in our previous study and blindly applied to current trial participants. Ninety-four chronic low back pain (CLBP) patients were classified into predicted-PTxResp or predicted-PTxNonR and randomized into no treatment, placebo treatment, or naproxen treatment. To monitor analgesia, back pain intensity was collected twice a day: 3 weeks baseline, 6 weeks of treatment, and 3 weeks of washout. Eighty-nine CLBP patients were included in the intent-to-treat analyses and 77 CLBP patients in the per-protocol analyses. Both analyses showed similar results. At the group level, the predictive model performed remarkably well, dissociating the separate effect sizes of pure placebo response and pure active treatment response and demonstrating that these effects interacted additively. Pain relief was about 15% stronger in the predicted-PTxResp compared with the predicted-PTxNonR receiving either placebo or naproxen, and the predicted-PTxNonR successfully isolated the active drug effect. At a single subject level, the biosignature better predicted placebo nonresponders, with poor accuracy. One component of the biosignature (dorsolateral prefrontal cortex-precentral gyrus functional connectivity) could be generalized across 3 placebo studies and in 2 different cohorts-CLBP and osteoarthritis pain patients. This study shows that a biosignature can predict placebo response at a group level in the setting of a randomized controlled trial., (Copyright © 2021 International Association for the Study of Pain.)

Background: Few studies have measured the impact of dementia-related fear on daily functioning, despite its clinical relevance. Our aim was to determine the relationship between fear-avoidance of memory loss, perceived memory failures and self-reported quality of life in a community based sample of older adults using a novel fear of memory loss (FAM) scale., Methods: Sixty-seven older adults (59-81 years) completed a 23-item self-report scale designed to capture multi-faceted components of fear of memory loss, known as the FAM scale. Perceived memory failures were measured using the Memory Failures Scale (MFS) and quality of life was assessed using the Older Person's Quality of Life scale (OPQOL-35). Participants also completed the Wechsler Memory Scale (WMS-IV) as a measure of objective memory performance and the Depression, Anxiety and Stress Scales (DASS) and the Geriatric Anxiety Inventory (GAI) as measures of general anxiety., Results: The FAM scale demonstrated strong internal consistency (Cronbach's α = .82) and concurrent validity with the GAI ( r = .47). Three latent factors were observed: (1) fear-avoidance, (2) problematic beliefs and (3) affective resilience. After adjusting for objective memory performance and general anxiety, higher fear-avoidance significantly predicted increased perceived memory failures ( p = .014) and reduced quality of life ( p = .033)., Conclusions: Fear of memory loss predicts increased perceived memory failures and lower self-reported quality of life in a community sample of older adults. Based on these findings, we propose a preliminary fear-avoidance model that explains the development and maintenance of dementia-related functional disability in terms of psychological processes.

A person's level of education can affect their access to health care, and their health outcomes. Increasing rates of depression are another looming public health concern. Therefore, vulnerability is compounded for individuals who have a lower level of education and depression. Assessment of depressive symptoms is integral to many domains of health care including primary care and mental health specialty care. This investigation examined the degree to which education influences the psychometric properties of self-report items that measure depressive symptoms. This study was a secondary data analysis derived from three large internet panel studies. Together, the studies included the Beck Depression Inventory-II, the Center for Epidemiologic Studies Depression Scale, the Patient Health Questionnaire, and the Patient Reported Outcomes Measurement Information System measures of depression. Using a differential item functioning (DIF) approach, we found evidence of DIF such that some items on each of the questionnaires were flagged for DIF with effect sizes ranging from McFadden's Pseudo R 2 = .005 to .022. For example, results included several double-barreled questions flagged for DIF. Overall, questionnaires assessing depression vary in level of complexity, which interacts with the respondent's level of education. Measurement of depression should include consideration of possible educational disparities, to identify people who may struggle with a written questionnaire, or may be subject to subtle psychometric biases associated with education.

This study explores the narrative contents obtained from the description of autobiographical memories reported by a sample of incarcerated males that exemplified their most aggressive, transgressive, or criminal selves. Participants were 110 men serving a prison sentence for different types of crimes. Three main phenomena were identified from their stories: the narration of the criminal self, description of the crime (or crimes) committed, and the criminal responsibility attributional processes. The results showed the existence of mechanisms to justify the crime among a large section of participants, whereas the assumption of personal responsibility for the commission of the crime and the consideration of an unfair or excessive sentence were not as frequent. Also, some specific crimes concurred with concrete responsibility attributional processes, especially with the justification of criminal behavior. These findings generate useful information regarding recidivism, resocialization, and the attribution of responsibility among inmates.

Background/objectives: Older children with atopic dermatitis (AD) suffer from poor sleep and attention problems. However, until recently, the dearth of developmentally sensitive assessment tools impeded characterization in younger children. We aimed to characterize sleep and attention problems in young children with AD and identify modifiable factors., Methods: A cross-sectional study of children with AD aged 1-4 years was stratified by disease severity (Patient-Oriented Eczema Measure), age, and racial/ethnic groups. Developmentally sensitive surveys assessed attention (Multidimensional Assessment Profile of Attention Regulation), sleep, and itch (Patient-Reported Outcomes Measurement Information System). Linear regression models identified predictors of sleep health and attention dysregulation., Results: Parents (n = 60) of children aged 2.78 ± 0.98 years with severe (n = 25), moderate (n = 25), or mild (n = 10) AD were recruited across the United States. Significantly reduced sleep health (T-score ≥ 60) was reported in 86% of children with moderate/severe disease (n = 43), and 50% had ≥5 nights of disturbed sleep per week. A suboptimal sleep environment was identified with 32% of children with too much light, noise, or electronic device usage. With regard to attention regulation, in children with severe AD, 80% had trouble sitting still and 72% of children had trouble paying attention no matter their surroundings. In fully adjusted models, AD severity was a significant predictor of poor sleep health (B = 0.79 [0.31-1.28], p < .01) and attention dysregulation (B = 1.22 [0.51-1.93], p < .01)., Conclusions: More severe AD correlates with poor sleep health and attention dysregulation. In addition to aggressive treatment of AD, clinicians should advise on modifiable sleep hygiene practices and consider screening for attention dysregulation in young children., (© 2021 Wiley Periodicals LLC.)

Background: Preventing transition to chronic back pain (CBP) is a long-sought strategy that could rescue patients from prolonged suffering. Recent rodent and human brain imaging studies suggest involvement of sexually dimorphic, dopaminergic-motivational, mesolimbic circuits in the transition to chronic pain (tCBP), and hint that the combination of carbidopa/levodopa and naproxen (LDP + NPX) may block tCBP. Here we evaluated, in people with recent-onset back pain, whether a 3-month treatment with LDP + NPX is safe, blocks tCBP, and whether its efficacy is sex-dependent., Methods: A total of 72 participants were enrolled and stratified by risk for tCBP using brain-imaging biomarkers. Low-risk participants entered a no-treatment arm. Others were randomized to placebo + naproxen or LDP + NPX for 3 months., Results: Both treatments resulted in more than 50% pain relief for approximately 75% of participants. A strong sex by treatment interaction was observed for daily pain intensity (phone NRS, P = 0.007), replicated on 4-week average pain (Pain/4w, P = 0.00001), and in intent-to-treat analysis (Pain/4w, P = 0.000004). Nucleus accumbens functional connectivity with medial prefrontal cortex, a predefined objective biomarker, showed sex dependence at baseline (P = 0.03) and sex-by-treatment interaction effect 3 months after treatment cessation (P = 0.031). Treatment modified the psychological profile of participants, and disrupted brain modeling-based predicted back pain intensity trajectories. Forty participants were queried 3.3 years from trial start; back pain ratings were similar between end of treatment and at 3.3 years (P = 0.62), indicating persistence of relief for this duration., Conclusions: These results provide the first evidence for preventing transition to chronic back pain using sex-specific pharmacotherapy. These provocative observations require confirmation in a larger study. ClinicalTrials.gov identifier: NCT01951105., (© 2021. The Author(s).)

Pain relief, or a decrease in self-reported pain intensity, is frequently the primary outcome of pain clinical trials. Investigators commonly report pain relief in one of two ways: using raw units (additive) or using percentage units (multiplicative). However, additive and multiplicative scales have different assumptions and are incompatible with one another. In this work, we describe the assumptions and corollaries of additive and multiplicative models of pain relief to illuminate the issue from statistical and clinical perspectives. First, we explain the math underlying each model and illustrate these points using simulations, for which readers are assumed to have an understanding of linear regression. Next, we connect this math to clinical interpretations, stressing the importance of statistical models that accurately represent the underlying data; for example, how using percent pain relief can mislead clinicians if the data are actually additive. These theoretical discussions are supported by empirical data from four longitudinal studies of patients with subacute and chronic pain. Finally, we discuss self-reported pain intensity as a measurement construct, including its philosophical limitations and how clinical pain differs from acute pain measured during psychophysics experiments. This work has broad implications for clinical pain research, ranging from statistical modeling of trial data to the use of minimal clinically important differences and patient-clinician communication., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Vigotsky, Tiwari, Griffith and Apkarian.)

Background: Atopic dermatitis (AD) causes sleep disturbance but the epidemiology is not known., Objective: To estimate the US prevalence of sleep disturbance and its impact on psychological and neurocognitive function., Methods: We conducted a cross-sectional survey of 180 parent-child dyads with AD using stratified sampling based on disease severity (Patient Oriented Eczema Measure: mild [n = 30), moderate (n = 75) or severe (n = 75]), age, and race (White or Black or African American or other). Symptoms of sleep and psychologic health were assessed using the Patient-Reported Outcome Measurement Information System. To estimate the prevalence of sleep disturbance, we calculated weights using poststratification adjustment making marginal frequencies of AD severity, race, and age similar to marginal frequencies in the 2007 National Survey of Children's Health. Unweighted regression models examined associations with sleep disturbance., Results: In children age 5 to 17 years with AD, we estimated that sleep disturbance occurred in 66.9% (95% confidence interval, 53.3% to 80.5%; 3,116,305 children). The odds of severe sleep disturbance (worse than 95% of US children) were highest in moderate to severe versus mild AD (2.03 [1.00-4.10]; P = .0495; compared with 8.68 [1.82-41.49]; P = .0068). Predictors of parent proxy-reported sleep disturbance were itch intensity (adjusted β [95% confidence interval] 1.33 [0.62-2.04]) and low income (<$50,000: 6.64 [2.05-11.23]; and $50,000 to less than 100,000: 4.75 [0.35-9.14]). Controlling for disease severity, itch intensity, and significant sociodemographics-parent-proxy, reported sleep disturbance was associated with increased severity of sleep-related impairment, depression, fatigue, and anxiety, in addition to worse inattention and impulsivity. In fully adjusted models, children who self-reported sleep disturbance (T-score ≥60) had increased odds of sleep-related impairment (1.20 [1.11-1.29]), depression (1.13 [1.03, 1.24]), fatigue (1.28 [1.06-1.54]), and anxiety (1.16 [1.02-1.31])., Conclusions: Sleep disturbance is a common symptom of AD. It affects about 3 million US children and is associated with neuropsychiatric impairment, including depression, anxiety, and inattention. Clinicians should screen for these symptoms in school-aged children, particularly those with moderate to severe AD., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

A cardinal feature of COVID-19 is lung inflammation and respiratory failure. In a prospective multi-country cohort of COVID-19 patients, we found that increased Notch4 expression on circulating regulatory T (Treg) cells was associated with disease severity, predicted mortality, and declined upon recovery. Deletion of Notch4 in Treg cells or therapy with anti-Notch4 antibodies in conventional and humanized mice normalized the dysregulated innate immunity and rescued disease morbidity and mortality induced by a synthetic analog of viral RNA or by influenza H1N1 virus. Mechanistically, Notch4 suppressed the induction by interleukin-18 of amphiregulin, a cytokine necessary for tissue repair. Protection by Notch4 inhibition was recapitulated by therapy with Amphiregulin and, reciprocally, abrogated by its antagonism. Amphiregulin declined in COVID-19 subjects as a function of disease severity and Notch4 expression. Thus, Notch4 expression on Treg cells dynamically restrains amphiregulin-dependent tissue repair to promote severe lung inflammation, with therapeutic implications for COVID-19 and related infections., Competing Interests: Declaration of interests T.A.C., H.H., M.B., P.S.L., P.C., and R.D.P. are inventors on provisional patent application US 63/038,186 titled “Methods and Compositions for treating coronavirus infectious disease.” H.H. and T.A.C. are co-founders of and hold equity in Alcea Therapeutics., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: We sought to determine the time-lagged, bidirectional relationships among clinical variables of pelvic pain, urinary symptoms, negative mood, nonpelvic pain and quality of life in men and women with urological chronic pelvic pain syndrome, incorporating interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome., Materials and Methods: A total of 204 female and 166 male patients were assessed up to 24 times over a 48-week period on the 5 primary outcomes. A lagged autoregressive analysis was applied to determine the directional relationship of one variable to another 2 weeks later, beyond that of the concurrent relationships at each time point and autocorrelations and trends over time., Results: The results show clear evidence for a bidirectional positive relationship between changes in pelvic pain severity and urinary symptom severity. Increases in either variable predicted significant increases in the other 2 weeks later, beyond that explained by their concurrent relationship at each time point. Pelvic pain and to a lesser degree urinary frequency also showed similar bidirectional relationships with negative mood and decreased quality of life. Interestingly, neither pelvic pain or urinary symptom severity showed lagged relationships with nonpelvic pain severity., Conclusions: Results document for the first time specific short-term positive feedback between pelvic pain and urinary symptoms, and between symptoms of urological chronic pelvic pain syndrome, mood and quality of life. The feedforward aspects of these relationships can facilitate a downward spiral of increased symptoms and worsening psychosocial function, and suggest the need for multifaceted treatments and assessment to address this possibility in individual patients.

Background: People who have migrated or with a language barrier may face significant hurdles in accessing health care. Some apps have been specifically developed to facilitate the dialogue between health care professionals and people who have migrated who have low-level language proficiency or to promote health among people who have migrated., Objective: We conducted a systematic review to investigate development, acceptability, and effectiveness of these types of apps., Methods: We conducted a search of PubMed, Scopus, and Embase databases. We included all study designs (qualitative, quantitative, mixed) reporting development, evaluation of efficacy, or acceptability of apps facilitating dialogue with a health professional or promoting health for people who have migrated, minorities, or tourists with a language barrier, using any outcome. Two researchers selected the studies independently. We collected general information about the app, information about health literacy and cultural adaptation, information about the development of the app, evidence on acceptability or efficacy, and information on app use. Data were collected by 2 researchers independently and results were reviewed to verify agreement and reported according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-analysis)., Results: Positive results for translation apps included better communication, but with possible limitations, and reduced consultation time. Positive results for health promotion apps included improved quality of life and better management of chronic illnesses., Conclusions: Overall, the apps had good levels of acceptability, though only half had their efficacy evaluated. In those evaluations, the endpoints were mostly related to reported behavior change and knowledge improvement, which is common for evaluations of health promotion programs. In the future, as more health apps are created, it is essential that apps that claim to have a public health objective undergo a rigorous evaluation of their acceptability, efficacy, and actual use. Indicators of outcomes beyond changes in behavior and knowledge should be reported; change in health status or access to care should also be reported. This systematic review has helped us note the characteristics associated with improved acceptability and efficacy, which can be helpful for the development of future apps., (©Frédérique Thonon, Swati Perrot, Abhijna Vithal Yergolkar, Olivia Rousset-Torrente, James W Griffith, Olivier Chassany, Martin Duracinsky. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 06.05.2021.)

Background: Late diagnoses of HIV, hepatitis B, and hepatitis C are important public health problems that affect the population at large and migrants in particular. Missed opportunities of HIV and hepatitis screening are numerous, with language differences being a significant barrier to testing. Several studies have shown that migrants who do not speak the language of the health provider are less likely to get tested, due to health providers' reluctance to offer a test and to migrants' reluctance to accept testing., Objective: The aim of our study is to develop a multilingual electronic tool (app) that assists health providers in offering and explaining HIV and hepatitis screenings to migrants with a language barrier and to evaluate its acceptability and impact in terms of public health., Methods: The study will go through 3 stages: (1) concept development, (2) app development, and (3) app evaluation. A qualitative study has been undertaken to explore language barriers during health care encounters and their effect on communication, specifically when a screening test is offered. In parallel, a systematic review of the literature was conducted to have a comprehensive overlook of electronic tools designed to help health care providers communicate with migrants with a language barrier. To generate a list of items to be translated for inclusion in the app, we will conduct a focus group and Delphi survey. The development of the app will include translation and voice recording of items. The electronic development will also include 3 steps of user testing. The acceptability of the app will be evaluated using the System Usability Scale. Evaluation of the app's efficacy will consist of a stepped wedge randomized controlled trial. The study will be carried out in 16 centers that treat migrants and offer them screening tests for infectious diseases. The primary outcome is the percentage of screening tests realized. The secondary outcomes are the rate of screening proposal by health professionals, acceptance rate by migrants, number of positive cases using this app, and frequency of use of the app., Results: The app evaluation study received a 3-year grant from the Agence Nationale de la Recherche contre le SIDA et les hépatites virales (ANRS) and from the Office Français de l'Immigration et Intégration (OFII). At the time of publication of this protocol, the initial qualitative study and systematic literature review were completed., Conclusions: This study will develop an app that assists health providers in offering and explaining HIV and hepatitis screenings to migrants with a language barrier and measure its acceptability and effectiveness in terms of public health. When completed, this app could be distributed to numerous professionals carrying out screening with migrant populations in various health care settings., International Registered Report Identifier (irrid): PRR1-10.2196/22239., (©Frédérique Thonon, Saleh Fahmi, Olivia Rousset-Torrente, Pascal Bessonneau, James W Griffith, Carter Brown, Olivier Chassany, Martin Duracinsky. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 05.05.2021.)

Background: Cognitive outcomes are an important determinant of quality of life after critical illness, but methods to assess early cognitive impairment and cognition recovery are not established. The objective of this study was to assess the feasibility and validity of objective and patient-reported cognition assessments for generalized use during early recovery from critical illness., Methods: Patients presented from the community with acute onset of either intracerebral hemorrhage (ICH) or sepsis as representative neurologic and systemic critical illnesses. Early cognitive assessments comprised the Glasgow Coma Scale (GCS), three NIH Toolbox cognition measures (Flanker Inhibitory Control and Attention Test, List Sorting Working Memory Test and Pattern Comparison Processing Speed Test) and two Patient Reported Outcomes Measurement Information System (PROMIS) cognition measures (Cognition-General Concerns and Cognition-Abilities) performed seven days after intensive care unit discharge or at hospital discharge, whichever occurred first., Results: We enrolled 91 patients (53 with sepsis, 38 with ICH), and after attrition principally due to deaths, cognitive assessments were attempted in 73 cases. Median [interquartile range] Sequential Organ Failure Assessment scores for patients with sepsis was 7 [3, 11]. ICH cases included 13 lobar, 21 deep and 4 infratentorial hemorrhages with a median [IQR] ICH Score 2 [1, 2]. Patient-reported outcomes were successfully obtained in 42 (58% overall, 79% of sepsis and 34% of ICH) patients but scores were anomalously favorable (median 97th percentile compared to the general adult population). Analysis of the PROMIS item bank by four blinded, board-certified academic neurointensivists revealed a strong correlation between higher severity of reported symptoms and greater situational relevance of the items (ρ = 0.72, p = 0.002 correlation with expert item assessment), indicating poor construct validity in this population. NIH Toolbox tests were obtainable in only 9 (12%) patients, all of whom were unimpaired by GCS (score 15) and completed PROMIS assessments. Median scores were 5th percentile (interquartile range [2nd, 9th] percentile) and uncorrelated with self-reported symptoms. Shorter intensive care unit length of stay was associated with successful testing in both patients with ICH and sepsis, along with lower ICH Score in patients with ICH and absence of premorbid dementia in patients with sepsis (all p < 0.05)., Conclusions: Methods of objective and patient-reported cognitive testing that have been validated for use in patients with chronic medical and neurologic illness were infeasible or yielded invalid results among a general sample of patients in this study who were in early recovery from neurologic and systemic critical illness. Longer critical illness duration and worse neurocognitive impairments, whether chronic or acute, reduced testing feasibility.

Introduction: We created and tested a mobile app that facilitates the ecological momentary assessment of pain intensity and pain location and identifies heterogeneous patient pain phenotypes., Methods: A mobile app was created with patient, clinician and researcher input. A sample of 20 participants with urologic chronic pelvic pain syndrome were then asked to complete a 14-day pain assessment using the app. Data were analyzed to assess compliance, usability and the ability for the app to capture variation in pain intensity and pain location. Ecological momentary assessment pain data were then compared to end-of-week pain summary questions to determine construct validity., Results: Mean compliance was 70±8%, higher earlier in the study period (p <0.0005) and better in older individuals (p <0.0001). During the 14-day assessment, 90% of participants reported daily variation in pelvic pain intensity (SD 0.64-3.02; out of 10), 95% reported variation in their nonpelvic pain (SD 0.17-3.63; out of 10) and 100% reported variations in number of sites with pain (SD 0.22-1.44; out of 7). Pelvic pain and nonpelvic pain intensity, as determined by cumulative app scores, were associated with patient reported end-of-week scores; worst pain ( r pelvic =0.67; r nonpelvic =0.53) and average pain ( r pelvic =0.78; r nonpelvic =0.73)., Conclusions: The easy-to-use app captured unique patterns of pain not fully captured by traditional end-of-day/week summary questions or by traditional in-office assessments. Mobile apps for assessing chronic conditions will become increasingly important as telehealth becomes more commonplace., (© 2021 by American Urological Association Education and Research, Inc.)