Association of smoking with neurocognition, inflammatory and myeloid cell activation profiles in people with HIV on ART.

OBJECTIVE: People with HIV (PWH) experience excess comorbidities, including neurocognitive disorders, which are linked to inflammation, particularly monocyte-macrophage activation. Smoking contributes to morbidity and mortality in well-treated PWH. We investigated associations between smoking, neurocognitive function, and inflammation in PWH on ART. DESIGN: We used baseline data on cognition and inflammation from a longitudinal study of virologically-suppressed PWH who do and do not smoke. METHODS: Participants completed 4 neurocognitive tests (7 measures), with a composite score as the primary measure. Inflammatory markers were plasma sCD14, sCD163, and CCL2/MCP-1; %CD14+ monocytes expressing CD16, CD163, and CCR2; and %CD8+ T cells co-expressing CD38/HLA-DR. Exploratory analyses included a plasma cytokine/chemokine panel, neurofilament light chain (NFL), hsCRP and monocyte transcriptomes by RNAseq. RESULTS: We recruited 58 PWH (26 current smoking [PWH/S], 32 no current smoking [PWH/NS]). Mean composite and individual neurocognitive scores did not differ significantly by smoking status except for the color shape task; PWH/S exhibited worse cognitive flexibility, with adjusted mean times 317.2 (95%CI 1.4, 632.9) msec longer than PWH/NS. PWH/S had higher plasma sCD14 than PWH/NS (median(IQR) 1820(1678, 2105) versus 1551(1284, 1760) ng/ml, p=0.009). Other inflammatory markers were not significantly different between PWH/S and PWH/NS. Monocyte transcriptomes showed several functions, regulators and gene sets that differed by smoking status. CONCLUSIONS: sCD14, a marker of monocyte activation, is elevated in PWH who smoke. While neurocognitive measures and other inflammatory markers did not generally differ, these data implicate smoking-related myeloid activation and monocyte gene dysregulation in the HIV/smoking synergy driving HIV-associated comorbidities.

Modulation of circulating free testosterone fraction by testosterone, dihydrotestosterone, and estradiol during testosterone replacement therapy.

BACKGROUND: Testosterone, estradiol, and dihydrotestosterone share common ligand binding sites on sex hormone binding globulin and albumin. It is unknown whether and how changes in testosterone, dihydrotestosterone, and estradiol concentrations during testosterone replacement therapy affect free testosterone fraction. OBJECTIVE: To determine the effect of changes in testosterone, dihydrotestosterone, and estradiol concentrations on free testosterone fraction during testosterone replacement therapy of men with hypogonadism. METHODS: Using data from the Testosterone Trials, we assessed the association of changes in total testosterone, estradiol, and dihydrotestosterone concentrations over 12 months of testosterone replacement therapy with changes in free testosterone fraction, measured using equilibrium dialysis. We used random forests to evaluate the associations of predicted mean changes in free testosterone fraction with changes in circulating concentrations of each hormone at low, mean, or high change in the other two hormones. RESULTS: Testosterone replacement therapy not only increased total testosterone, dihydrotestosterone, estradiol, and free testosterone concentrations, but also the percent free testosterone, even though sex hormone binding globulin levels did not change. The predicted changes in free testosterone fraction during testosterone replacement therapy exhibited a non-linear relationship with changes in each of total testosterone, dihydrotestosterone, and estradiol concentrations. Greater increases in testosterone, dihydrotestosterone, and estradiol levels during testosterone replacement therapy were each associated with higher model-predicted percent free testosterone. Substantially smaller changes in molar concentrations of estradiol and dihydrotestosterone had a greater effect on percent free testosterone than those in testosterone. CONCLUSION: During testosterone replacement therapy of men with hypogonadism, changes in testosterone, dihydrotestosterone, and estradiol concentrations each altered percent free testosterone non-linearly. Small changes in estradiol concentrations exerted much larger effect on the free testosterone fraction than testosterone and dihydrotestosterone, suggesting complex interactions of the three hormones with the binding proteins. Assessment of changes in free testosterone during testosterone replacement therapy should include consideration of changes in all three hormones.

University of Pennsylvania Telehealth Research Center of Excellence.

Drawing from insights from communication science and behavioral economics, the University of Pennsylvania Telehealth Research Center of Excellence (Penn TRACE) is designing and testing telehealth strategies with the potential to transform access to care, care quality, outcomes, health equity, and health-care efficiency across the cancer care continuum, with an emphasis on understanding mechanisms of action. Penn TRACE uses lung cancer care as an exemplar model for telehealth across the care continuum, from screening to treatment to survivorship. We bring together a diverse and interdisciplinary team of international experts and incorporate rapid-cycle approaches and mixed methods evaluation in all center projects. Our initiatives include a pragmatic sequential multiple assignment randomized trial to compare the effectiveness of telehealth strategies to increase shared decision-making for lung cancer screening and 2 pilot projects to test the effectiveness of telehealth to improve cancer care, identify multilevel mechanisms of action, and lay the foundation for future pragmatic trials. Penn TRACE aims to produce new fundamental knowledge and advance telehealth science in cancer care at Penn and nationally.

Comparison of Sales From Vending Machines With 4 Different Food and Beverage Messages: A Randomized Trial.

Importance: Point-of-sale food messaging can encourage healthier purchases, but no studies have directly compared multiple interventions in the field. Objective: To examine which of 4 food and beverage messages would increase healthier vending machine purchases. Design, Setting, and Participants: This randomized trial assessed 13 months (February 1, 2019, to February 29, 2020) of vending sales data from 267 machines and 1065 customer purchase assessments from vending machines on government property in Philadelphia, Pennsylvania. Data analysis was performed from March 5, 2020, to November 8, 2022. Interventions: Study interventions were 4 food and beverage messaging systems: (1) beverage tax posters encouraging healthy choices because of the Philadelphia tax on sweetened drinks; (2) green labels for healthy products; (3) traffic light labels: green (healthy), yellow (moderately healthy), or red (unhealthy); or (4) physical activity equivalent labels (minutes of activity to metabolize product calories). Main Outcomes and Measures: Sales data were analyzed separately for beverages and snacks. The main outcomes analyzed at the transaction level were calories sold and the health status (using traffic light criteria) of each item sold. Additional outcomes were analyzed at the monthly machine level: total units sold, calories sold, and units of each health status sold. The customer purchase assessment outcome was calories purchased per vending trip. Results: Monthly sales data came from 150 beverage and 117 snack vending machines, whereas 1065 customers (558 [52%] male) contributed purchase assessment data. Traffic light labels led to a 30% decrease in the mean monthly number of unhealthy beverages sold (mean ratio [MR], 0.70; 95% CI, 0.55-0.88) compared with beverage tax posters. Physical activity labels led to a 34% (MR, 0.66; 95% CI, 0.51-0.87) reduction in the number of unhealthy beverages sold at the machine level and 35% (MR, 0.65; 95% CI, 0.50-0.86) reduction in mean calories sold. Traffic light labels also led to a 30-calorie reduction (b = -30.46; 95% CI, -49.36 to -11.56) per customer trip in the customer purchase analyses compared to physical activity labels. There were very few significant differences for snack machines. Conclusions and Relevance: In this 13-month randomized trial of 267 vending machines, the traffic light and physical activity labels encouraged healthier beverage purchases, but no change in snack sales, compared with a beverage tax poster. Corporations and governments should consider such labeling approaches to promote healthier beverage choices. Trial Registration: ClinicalTrials.gov Identifier: NCT06260176.

Comparative Effectiveness of Perioperative Antibiotic Regimens to Prevent Surgical Site Infections in Pediatric Liver Transplant Recipients.

BACKGROUND: Surgical site infections (SSIs) are a common complication in liver transplant (LT) recipients. Lack of pediatric prophylaxis guidelines results in variation in preventative antibiotic regimens. METHODS: We performed a retrospective observational study of LT recipients <18 years old using a merged data set that included data from the Pediatric Health Information System and the United Network for Organ Sharing between 2006 and 2017. The exposure was defined as the antibiotic(s) received within 24 hours of LT, with 6 categories, ranging from narrow (category 1: cefazolin), to broad). The primary outcome was presence or absence of SSI in the index admission. Mixed-effects logistic regression compared the effectiveness of each category in preventing SSI, relative to category 1. RESULTS: Of the 2586 LT, 284 (11%) met SSI criteria. The SSI rate was higher in the younger subcohort (16.2%) than in the older (8.6%), necessitating a stratified analysis. Antibiotics from category 5 were most commonly used. In the younger subcohort, the adjusted risk was increased in all categories compared with the reference, most notably in category 3 (odds ratio [OR], 2.58 [95% confidence interval: .69-9.59]) and category 6 (2.76 [.66-11.56]). In the older subcohort, estimated ORs were also increased for each category, most notably in category 4 (2.49 [95% confidence interval: .99-6.27]). None of the ORs suggested benefit from broader-spectrum prophylaxis. Our E-value assessment suggests that it's unlikely there is unmeasured confounding by indication to the degree necessary to revert ORs to protective. CONCLUSIONS: There was wide variation in antibiotic prophylaxis. Adjusted analyses did not reveal a protective benefit of broader-spectrum prophylaxis in either subcohort, suggesting that narrower regimens may be adequate.

Marshall Joffe's Contributions to Causal Inference, Biostatistics, and Epidemiology.

We pay tribute to Marshall Joffe, PhD, and his substantial contributions to the field of causal inference with focus in biostatistics and epidemiology. By compiling narratives written by us, his colleagues, we not only present highlights of Marshall's research and their significance for causal inference but also offer a portrayal of Marshall's personal accomplishments and character. Our discussion of Marshall's research notably includes (but is not limited to) handling of posttreatment variables such as noncompliance, employing G-estimation for treatment effects on failure-time outcomes, estimating effects of time-varying exposures subject to time-dependent confounding, and developing a causal framework for case-control studies. We also provide a description of some of Marshall's unpublished work, which is accompanied by a bonus anecdote. We discuss future research directions related to Marshall's research. While Marshall's impact in causal inference and the world outside of it cannot be wholly captured by our words, we hope nonetheless to present some of what he has done for our field and what he has meant to us and to his loved ones.

Use of the Bath Ankylosing Spondylitis Disease Activity Index in Patients With Psoriatic Arthritis With and Without Axial Disease.

OBJECTIVE: To evaluate whether the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a responsive instrument in psoriatic arthritis (PsA) and whether it differentiates between axial and peripheral disease activity in PsA. METHODS: Individuals with PsA initiating therapy in a longitudinal cohort study based in the United States were included. Axial PsA (axPsA), most often also associated with peripheral disease, was defined as fulfillment of the Assessment of Spondyloarthritis international Society axial spondyloarthritis classification criteria or presence of axial disease imaging features. Baseline BASDAI, individual BASDAI items, patient global assessment, patient pain, and Routine Assessment of Patient Index Data 3, and score changes following therapy initiation were descriptively reported. Standardized response means (SRMs) were calculated as the mean change divided by the SD of the change. RESULTS: The mean (SD) baseline BASDAI score at the time of therapy initiation was 5.0 (2.2) among those with axPsA (n = 40) and 4.8 (2.0) among those with peripheral-only disease (n = 79). There was no significant difference in patient-reported outcome scores between the groups. The mean change for BASDAI was similar among axial vs peripheral disease (-0.75 vs -0.83). SRMs were similar across axial vs peripheral disease for BASDAI (-0.37 vs -0.44) and the individual BASDAI items. CONCLUSION: BASDAI has reasonable responsiveness in PsA but does not differentiate between axPsA and peripheral PsA. (ClinicalTrials.gov: NCT03378336).

Clinician Prompts for Human Papillomavirus Vaccination: A Cluster Randomized Trial.

OBJECTIVE: We assessed the impact of an online intervention using clinician prompts for human papillomavirus (HPV) vaccination with a cluster randomized controlled trial. METHODS: The randomized trial occurred July 2021-January 2022 in 48 primary care pediatric practices (24 intervention, 24 control) across the US. We trained clinicians via two online learning modules, plus weekly ''quick tips'' delivered via text or email. The training taught practices to implement a staff prompt to the clinician (e.g., printed reminders placed on the keyboard) plus electronic health record (EHR) prompts (if not already done) at well and acute/chronic visits for initial and subsequent HPV vaccination. We assessed missed opportunities for HPV vaccination using logistic regression models accounting for clustering by practice on an intent to treat basis. Surveys assessed facilitators and barriers to using prompts. RESULTS: During the 6-month intervention, missed opportunities for HPV vaccination increased (worsened) in both intervention and control groups. However, at well child care visits, missed opportunities for the initial HPV vaccine increased by 4.5 (95% CI: -9.0%, -0.1%) percentage points less in intervention versus control practices. Change in missed opportunities for subsequent doses at well child care and non-well child care visits did not differ between trial groups. An end-of trial survey found understaffing as a common challenge. CONCLUSIONS: Clinician prompts reduced missed opportunities for HPV vaccination at well child care visits. Understaffing related to the COVID-19 pandemic may have led to worsening missed opportunities for both groups and likely impeded practices in fully implementing changes.

Incidence, Microbiological Studies, and Factors Associated With Prosthetic Joint Infection After Total Knee Arthroplasty.

Importance: Despite the frequency of total knee arthroplasty (TKA) and clinical implications of prosthetic joint infections (PJIs), knowledge gaps remain concerning the incidence, microbiological study results, and factors associated with these infections. Objectives: To identify the incidence rates, organisms isolated from microbiological studies, and patient and surgical factors of PJI occurring early, delayed, and late after primary TKA. Design, Setting, and Participants: This cohort study obtained data from the US Department of Veterans Affairs (VA) Corporate Data Warehouse on patients who underwent elective primary TKA in the VA system between October 1, 1999, and September 30, 2019, and had at least 1 year of care in the VA prior to TKA. Patients who met these criteria were included in the overall cohort, and patients with linked Veterans Affairs Surgical Quality Improvement Program (VASQIP) data composed the VASQIP cohort. Data were analyzed between December 9, 2021, and September 18, 2023. Exposures: Primary TKA as well as demographic, clinical, and perioperative factors. Main Outcomes and Measures: Incident hospitalization with early, delayed, or late PJI. Incidence rate (events per 10 000 person-months) was measured in 3 postoperative periods: early (≤3 months), delayed (between >3 and ≤12 months), and late (>12 months). Unadjusted Poisson regression was used to estimate incidence rate ratios (IRRs) with 95% CIs of early and delayed PJI compared with late PJI. The frequency of organisms isolated from synovial or operative tissue culture results of PJIs during each postoperative period was identified. A piecewise exponential parametric survival model was used to estimate IRRs with 95% CIs associated with demographic and clinical factors in each postoperative period. Results: The 79 367 patients (median (IQR) age of 65 (60-71) years) in the overall cohort who underwent primary TKA included 75 274 males (94.8%). A total of 1599 PJIs (2.0%) were identified. The incidence rate of PJI was higher in the early (26.8 [95% CI, 24.8-29.0] events per 10 000 person-months; IRR, 20.7 [95% CI, 18.5-23.1]) and delayed periods (5.4 [95% CI, 4.9-6.0] events per 10 000 person-months; IRR, 4.2 [95% CI, 3.7-4.8]) vs the late postoperative period (1.3 events per 10 000 person-months). Staphylococcus aureus was the most common organism isolated overall (489 [33.2%]); however, gram-negative infections were isolated in 15.4% (86) of early PJIs. In multivariable analyses, hepatitis C virus infection, peripheral artery disease, and autoimmune inflammatory arthritis were associated with PJI across all postoperative periods. Diabetes, chronic kidney disease, and obesity (body mass index of ≥30) were not associated factors. Other period-specific factors were identified. Conclusions and Relevance: This cohort study found that incidence rates of PJIs were higher in the early and delayed vs late post-TKA period; there were differences in microbiological cultures and factors associated with each postoperative period. These findings have implications for postoperative antibiotic use, stratification of PJI risk according to postoperative time, and PJI risk factor modification.

Effects of 4 Interpretive Front-of-Package Labeling Systems on Hypothetical Beverage and Snack Selections: A Randomized Clinical Trial.

Importance: Policymakers and researchers have proposed a variety of interpretative front-of-package food labeling systems, but it remains unclear which is most effective at encouraging people to choose healthier foods and beverages, including among people with less education. Objective: To test the effects of 4 interpretative front-of-package food labeling systems on the healthfulness of beverage and snack selections, overall and by education level. Design, Setting, and Participants: This randomized clinical trial of a national sample of US adults 18 years and older was conducted online from November 16 to December 3, 2022. Intervention: Participants were randomized to view products with 1 of 5 food labeling systems, including control (calorie labels only) or 1 of 4 interpretative labeling systems: green ("choose often") labels added to healthy foods; single traffic light labels added to healthy, moderately healthy, and unhealthy foods; physical activity calorie equivalent labels added to all products; and nutrient warning labels added to products high in calories, sugar, saturated fat, or sodium. All conditions had calorie labels on all products. Main Outcomes and Measures: Participants selected 1 of 16 beverages and 1 of 16 snacks that they wanted to hypothetically purchase. The primary outcomes were calories selected from beverages and from snacks. Secondary outcomes included label reactions and perceptions. Results: A total of 7945 participants completed the experiment and were included in analyses (4078 [51%] female, 3779 [48%] male, and 88 [1%] nonbinary or another gender; mean [SD] age, 47.5 [17.9 years]). Compared with the control arm, exposure to the green (average differential effect [ADE], -34.2; 95% CI, -42.2 to -26.1), traffic light (ADE, -31.5; 95% CI, -39.5 to -23.4), physical activity (ADE, -39.0; 95% CI, -47.0 to -31.1), or nutrient warning labels (ADE, -28.2; 95% CI, -36.2 to -20.2) led participants to select fewer calories from beverages (all P < .001). Similarly, compared with the control label, exposure to the green (ADE, -12.7; 95% CI, -17.3 to -8.2), traffic light (ADE, -13.7; 95% CI, -18.2 to -9.1), physical activity (ADE, -18.5; 95% CI, -23.1 to -13.9), or nutrient warning labels (ADE, -14.2; 95% CI, -18.8 to -9.6) led participants to select fewer calories from snacks (all P < .001). These effects did not differ by education level. The green labels were rated as less stigmatizing than the other interpretative systems but otherwise generally received the least favorable label reactions and perceptions (eg, elicited less attention, were perceived as less trustworthy), while the nutrient warnings and physical activity labels received the most favorable ratings. Conclusions and Relevance: In this randomized clinical trial of front-of-package food labeling systems, all 4 interpretative labeling systems reduced calories selected from beverages and from snacks compared with calorie labels, with no differences by education level. Trial Registration: ClinicalTrials.gov Identifier: NCT05432271.

Missed Opportunities for Adolescent Immunizations at Well-Care Visits During the COVID-19 Pandemic.

PURPOSE: The Coronavirus Disease 2019 pandemic disrupted healthcare, but the impact on vaccination missed opportunities (MOs, vaccine-eligible visits without vaccination) is unknown. We evaluated pandemic-related trends in MOs at adolescent well-care visits for three vaccines: human papillomavirus; quadrivalent meningococcal conjugate; and tetanus, diphtheria, and acellular pertussis (Tdap). METHODS: We analyzed electronic health record data from 24 pediatric primary care practices in 13 states from 1/1/2018 to 12/31/2021. Segmented logistic regression estimated risk differences for MOs during the pandemic relative to prepandemic trends. RESULTS: Among 106,605 well-care visits, we observed decreases in MOs prepandemic followed by an increase in MOs during the pandemic for all three vaccines. Relative to prepandemic, MOs increased for human papillomavirus (+15.9%, 95% confidence interval [CI]: 11.7%, 20.1%), meningococcal conjugate (+9.4%, 95% CI: 5.2%, 13.7%), and tetanus, diphtheria, and acellular pertussis (Tdap) (+ 8.2%, 95% CI: 4.3%, 12.1%). DISCUSSION: Increases in vaccine MOs during the pandemic equaled or exceeded pre-pandemic decreases. Reducing MOs in adolescent well-care could raise vaccine coverage.

Widespread Pain Phenotypes Impact Treatment Efficacy Results in Randomized Clinical Trials for Interstitial Cystitis/Bladder Pain Syndrome: A MAPP Network Study.

Clinical trials of pain are notoriously difficult and inefficient in demonstrating efficacy even for known efficacious treatments. Determining the appropriate pain phenotype to study can be problematic. Recent work has identified the extend of widespread pain as an important factor in the likelihood of response to therapy, but has not been tested in clinical trials. Using data from three previously published negative studies of the treatment of interstitial cystitis/ bladder pain with data on the extent of widespread pain, we examined the response of patients to different therapies base on the amount of pain beyond the pelvis. Participants with predominately local but not widespread pain responded to therapy targeting local symptoms. Participants with widespread and local pain responded to therapy targeting widespread pain. Differentiating patients with and without widespread pain phenotypes may be a key feature of designing future pain clinical trials to demonstrate treatments that are effective versus not.

Responsiveness and Minimum Clinically Important Difference in Patient-Reported Outcome Measures Among Patients With Psoriatic Arthritis: A Prospective Cohort Study.

OBJECTIVE: To determine the responsiveness to therapy and minimum clinically important improvement (MCII) for patient-reported outcome measures in psoriatic arthritis (PsA) and to examine the impact of baseline disease activity on the ability to demonstrate change. METHODS: A longitudinal cohort study was performed within the PsA Research Consortium. Patients completed several patient-reported outcomes, including the Routine Assessment of Patient Index Data, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Psoriatic Arthritis Impact of Disease 12-item (PsAID12) questionnaire, and others. The mean change in the scores between visits and standardized response means (SRMs) were calculated. The MCII was calculated as the mean change in score among patients who reported minimal improvement. SRMs and MCIIs were compared among subgroups with moderate to highly active PsA and those with lower disease activity. RESULTS: Among 171 patients, 266 therapy courses were included. The mean ± SD age was 51 ± 13.8 years, 53% were female, and the mean swollen and tender joint counts were 3 and 6, respectively, at baseline. SRMs and MCII for all measures were small to moderate, although greater among those with higher baseline disease activity. BASDAI had the best SRM overall and for less active PsA, and the clinical Disease Activity of PsA (cDAPSA) and PsAID12 were best for those with higher disease activity. CONCLUSION: SRMs and MCII were relatively small in this real-world population, particularly among those with lower disease activity at baseline. BASDAI, cDAPSA, and PsAID12 had good sensitivity to change, but selection for use in trials should consider the baseline disease activity of patients to be enrolled.

Clinically Important Differences for Pain and Urinary Symptoms in Urological Chronic Pelvic Pain Syndrome: A MAPP Network Study.

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.

Associations Between Urological Chronic Pelvic Pain Syndrome Symptom Flares, Illness Impact, and Health Care Seeking Activity: Findings From the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study.

PURPOSE: Most studies on interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome use typical or average levels of pelvic pain or urological symptom intensity as their outcome, as both are associated with reduced quality of life. Symptom exacerbations or "flares" have also been found to be associated with reduced quality of life, but no studies, to our knowledge, have investigated whether these associations are independent of typical pelvic pain levels and thus might be useful additional outcome measures (or stated differently, whether reducing flare frequency even without reducing mean pain intensity may be important to patients). MATERIALS AND METHODS: We used screening visit and weekly run-in period data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study to investigate associations between flare frequency and multiple measures of illness impact and health care seeking activity, independent of typical nonflare and overall pelvic pain levels. RESULTS: Among the 613 eligible participants, greater flare frequency was associated with worse condition-specific illness impact (standardized ß coefficients=0.11-0.68, P trends < .0001) and health care seeking activity (odds ratios=1.52-3.94, P trends .0039 to < .0001) in analyses adjusted for typical nonflare and overall pelvic pain levels. Experiencing ≥1/d was also independently associated with worse general illness impact (standardized ß coefficients=0.11-0.25). CONCLUSIONS: Our findings suggest that flare frequency and possibly other flare characteristics may be worth considering as additional outcome measures in urological chronic pelvic pain syndrome research to support the development of new preventive and therapeutic flare strategies.

Trends in Positive Depression and Suicide Risk Screens in Pediatric Primary Care During COVID-19.

OBJECTIVE: Adolescent mental health concerns increased during COVID-19, but it is unknown whether early increases in depression and suicide risk have been sustained. We examined changes in positive screens for depression and suicide risk in a large pediatric primary care network through May 2022. METHODS: Using an observational repeated cross-sectional design, we examined changes in depression and suicide risk during the pandemic using electronic health record data from adolescents. Segmented logistic regression was used to estimate risk differences (RD) for positive depression and suicide risk screens during the early pandemic (June 2020-May 2021) and late pandemic (June 2021-May 2022) relative to before the pandemic (March 2018-February 2020). Models adjusted for seasonality and standard errors accounted for clustering by practice. RESULTS: Among 222,668 visits for 115,627 adolescents (mean age 15.7, 50% female), the risk of positive depression and suicide risk screens increased during the early pandemic period relative to the prepandemic period (RD, 3.8%; 95% CI, 2.9, 4.8; RD, 2.8%; 95% CI, 1.7, 3.8). Risk of depression returned to baseline during the late pandemic period, while suicide risk remained slightly elevated (RD, 0.7%; 95% CI, -0.4, 1.7; RD, 1.8%; 95% CI, 0.9%, 2.7%). CONCLUSIONS: During the early months of the pandemic, there was an increase in positive depression and suicide risk screens, which later returned to prepandemic levels for depression but not suicide risk. Results suggest that pediatricians should continue to prioritize screening adolescents for depressive symptoms and suicide risk and connect them to treatment.

Performance Feedback for Human Papillomavirus Vaccination: A Randomized Trial From the American Academy of Pediatrics Pediatric Research in Office Settings Research Network.

OBJECTIVE: To test the hypothesis that a feedback-based intervention would reduce human papillomavirus (HPV) vaccine missed opportunities. METHODS: In a longitudinal cluster randomized controlled trial of 48 pediatric primary care practices, we allocated half the practices to receive a sequential, multicomponent intervention phased over consecutive periods. In a prior trial (period 1), communication skills training reduced missed opportunities for the initial HPV vaccine dose at well visits but not at acute/chronic visits. The current trial (period 2) evaluated the added value of performance feedback to clinicians after communication training. Performance feedback consisted of an introductory training module, weekly electronic "Quick Tips," and 3 individualized performance feedback reports to clinicians. We fit logistic regression models for the primary outcome of HPV vaccination missed opportunities using generalized estimating equations with independence working correlation, accounting for clustering at the practice level. RESULTS: Performance feedback resulted in a 3.4 (95% confidence interval [CI]: -6.8, 0.0) percentage point greater reduction in missed HPV vaccine opportunities for the intervention versus control group during acute/chronic visits for subsequent HPV vaccinations (dose 2 or 3). However, during well visits for HPV vaccination dose #1, intervention practices increased missed opportunities (worsened) by 4.2 (95% CI: 1.0, 7.4) percentage points more than control practices, reducing the prior period 1 improvements and blunting the overall effect of performance feedback. We did not observe differences for the other visit/dose categories. CONCLUSIONS: Performance feedback improved HPV vaccination for one subset of visits (acute/chronic, subsequent HPV vaccinations due), but not for well visits.

Predictors of Male Sexual Dysfunction in Urologic Chronic Pelvic Pain Syndrome (UCPPS), Other Chronic Pain Syndromes, and Healthy Controls in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

BACKGROUND: Sexual dysfunction (SD), including erectile (ED) and ejaculatory dysfunction, is associated with diminished quality of life (QoL) in men with UCPPS (chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and/or interstitial cystitis/bladder pain syndrome (IC/BPS)). AIM: We sought to compare SD among male patients with UCPPS, other chronic pain conditions (positive controls, PC), and healthy controls (HC) without chronic pain, and to evaluate the association of comorbidities, psychosocial factors, and urologic factors of SD in all 3 groups. METHODS: Baseline data from male UCPPS participants, PC (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia) and HC enrolled in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network Epidemiology and Phenotyping Study were included in the analysis. Sexual function was assessed using the International Index of Erectile Function-Erectile Function Domain (IIEFEF) and Ejaculatory Function Scale (EFS). Male ED was defined as a composite IIEF-EF score <21. Higher EFS score indicated worse sexual dysfunction; no threshold to define SD was identified for the EFS. Multivariable logistic and linear regression was used to investigate associations of comorbidities, psychosocial factors, and urologic factors with ED and ejaculatory, respectively. OUTCOMES: Comorbidities, genital pain, and psychosocial factors are associated with SD across the study population and male patients with UCPPS had a high prevalence of ED and greater ejaculatory dysfunction. RESULTS: There were 191 males with UCPPS; 44 PC; and 182 HC. Males with UCPPS had worse SD compared to PC and HC including lower mean IIEF-EF scores, greater degree of ejaculatory dysfunction, and lower quality of sexual relationships. Among all 3 cohorts, depression, stress, and pain were associated with ED in univariable and multivariable analysis, as was diabetes mellitus. Pain in the genitalia, severity of urinary symptoms, depression, stress, and history of childhood sexual trauma were associated with ejaculatory dysfunction in univariable and multivariable analysis. CLINICAL IMPLICATIONS: A multidisciplinary approach that addresses the identified risk factors for SD may improve overall QoL in males with UCPPS. STRENGTHS AND LIMITATIONS: Our study is strengthened by its use of validated, patient-reported questionnaires and inclusion of healthy and positive controls. Our understanding of the role of IC in this study is limited because only 1 patient in the study had IC/BPS as a sole diagnosis. CONCLUSIONS: When compared to healthy controls and patients with other chronic pain conditions, males with UCPPS experience higher degrees of SD, including erectile and ejaculatory dysfunction. Loh-Doyle JC, Stephens-Shields AJ, Rolston R, et al. Predictors of Male Sexual Dysfunction in Urologic Chronic Pelvic Pain Syndrome (UCPPS), Other Chronic Pain Syndromes, and Healthy Controls in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network. J Sex Med 2022;19:1804-1812.