mLiftOver: harmonizing data across Infinium DNA methylation platforms.

MOTIVATION: Infinium DNA methylation BeadChips are widely used for genome-wide DNA methylation profiling at the population scale. Recent updates to probe content and naming conventions in the EPIC version 2 (EPICv2) arrays have complicated integrating new data with previous Infinium array platforms, such as the MethylationEPIC (EPIC) and the HumanMethylation450 (HM450) BeadChip. RESULTS: We present mLiftOver, a user-friendly tool that harmonizes probe ID, methylation level, and signal intensity data across different Infinium platforms. It manages probe replicates, missing data imputation, and platform-specific bias for accurate data conversion. We validated the tool by applying HM450-based cancer classifiers to EPICv2 cancer data, achieving high accuracy. Additionally, we successfully integrated EPICv2 healthy tissue data with legacy HM450 data for tissue identity analysis and produced consistent copy number profiles in cancer cells. AVAILABILITY AND IMPLEMENTATION: mLiftOver is implemented R and available in the Bioconductor package SeSAMe (version 1.21.13+): https://bioconductor.org/packages/release/bioc/html/sesame.html. Analysis of EPIC and EPICv2 platform-specific bias and high-confidence mapping is available at https://github.com/zhou-lab/InfiniumAnnotationV1/raw/main/Anno/EPICv2/EPICv2ToEPIC_conversion.tsv.gz. The source code is available at https://github.com/zwdzwd/sesame/blob/devel/R/mLiftOver.R under the MIT license.

EndoPRS: Incorporating Endophenotype Information to Improve Polygenic Risk Scores for Clinical Endpoints.

Polygenic risk score (PRS) prediction of complex diseases can be improved by leveraging related phenotypes. This has motivated the development of several multi-trait PRS methods that jointly model information from genetically correlated traits. However, these methods do not account for vertical pleiotropy between traits, in which one trait acts as a mediator for another. Here, we introduce endoPRS, a weighted lasso model that incorporates information from relevant endophenotypes to improve disease risk prediction without making assumptions about the genetic architecture underlying the endophenotype-disease relationship. Through extensive simulation analysis, we demonstrate the robustness of endoPRS in a variety of complex genetic frameworks. We also apply endoPRS to predict the risk of childhood onset asthma in UK Biobank by leveraging a paired GWAS of eosinophil count, a relevant endophenotype. We find that endoPRS significantly improves prediction compared to many existing PRS methods, including multi-trait PRS methods, MTAG and wMT-BLUP, which suggests advantages of endoPRS in real-life clinical settings.

Split face randomized, evaluator blinded study on the effect of multiple subcisions on rolling acne scars.

Acne scarring results from a common inflammatory condition present in many people. These scars can have an impact on quality of life by influencing self-esteem and social acceptance. Current acne scarring treatments, such as chemical peels and laser treatments, often have limited success due to their time-consuming nature and the variability of acne scar types. The subcision technique has shown promise for the treatment of rolling acne scars. There are few studies to date that examine the effects of multiple subcision treatments on rolling acne scars. We evaluated whether the use of multiple subcision treatments improved the appearance of rolling acne scars compared to no treatment. Five patients with rolling acne scars on both sides of their face who met inclusion and exclusion criteria were enrolled in the study. One side of the face was randomized to receive treatment, while the contralateral side of the face received no treatment. Subjects underwent five sequential subcision treatments, spaced 4 weeks apart, with two follow-up visits at weeks 20 and 36 from the 1st treatment. Photographs were taken before and after the initial treatment visit and at each subsequent visit. Acne scar appearance was evaluated by the subject, a blinded live rater, and two double-blinded dermatologist raters. Evaluations of treatment outcomes involved overall acne scar appearance on a 5-point scale, acne scar improvement on a percentage scale, a modified quantitative global scarring grading system, and potential treatment side effects. There was a greater decrease in global scarring scores in the multiple subcision side compared to the control side. There was a greater difference in the average acne scar appearance scores between the Week 36 follow-up visit and baseline for the multiple subcision side compared to that of the control side. 50% of patients reported being more satisfied with the treatment side compared to the control side in regard to overall improvement. The study results suggest that multiple subcision treatments may improve the appearance of rolling acne scars compared to no treatment.

Proteome-wide association study using cis and trans variants and applied to blood cell and lipid-related traits in the Women's Health Initiative study.

In most Proteome-Wide Association Studies (PWAS), variants near the protein-coding gene (±1 Mb), also known as cis single nucleotide polymorphisms (SNPs), are used to predict protein levels, which are then tested for association with phenotypes. However, proteins can be regulated through variants outside of the cis region. An intermediate GWAS step to identify protein quantitative trait loci (pQTL) allows for the inclusion of trans SNPs outside the cis region in protein-level prediction models. Here, we assess the prediction of 540 proteins in 1002 individuals from the Women's Health Initiative (WHI), split equally into a GWAS set, an elastic net training set, and a testing set. We compared the testing r2 between measured and predicted protein levels using this proposed approach, to the testing r2 using only cis SNPs. The two methods usually resulted in similar testing r2, but some proteins showed a significant increase in testing r2 with our method. For example, for cartilage acidic protein 1, the testing r2 increased from 0.101 to 0.351. We also demonstrate reproducible findings for predicted protein association with lipid and blood cell traits in WHI participants without proteomics data and in UK Biobank utilizing our PWAS weights.

Best Practices in Documenting and Coding High-Value Care in Workers' Compensation Encounters-ACOEM Guidance Statement.

ABSTRACT: Workers' compensation outpatient care requires attention to causation, functional assessment, work disability prevention, and return-to-work planning, elements not usually addressed in other types of outpatient encounters. Because these elements of care deviate from the usual pattern of ambulatory services, providers of workers' compensation care have faced challenges in billing and auditing practices resulting in underpayment when providing high-value care based on evidence-based guidelines. Recent changes in Centers for Medicare & Medicaid Services rules on documentation requirements for coding outpatient evaluation and management encounters offer an opportunity for occupational health clinicians to be paid appropriately for care that follows occupational medicine practice guidelines. There remains a need to define the elements of documentation that should be expected in delivering high-value workers' compensation care. This article provides guidance for documenting high-value workers' compensation care.

Racial and Ethnic Disparities in Postpartum Depressive Symptoms Before and During the COVID-19 Pandemic.

Background: Existing evidence regarding the impact of the COVID-19 pandemic on postpartum mental health is mixed, with disparate studies showing increased, stable, or even reduced risk of postpartum depression (PPD) amid the pandemic. Furthermore, although it is plausible that the pandemic impacted the mental health of mothers from vulnerable and underserved communities differentially, few studies have characterized racial and ethnic differences in the impact of the COVID-19 pandemic on PPD. Materials and Methods: Pregnancy Risk Assessment Monitoring System data for 2018-2019 (pre-pandemic period) and 2020 (peri-pandemic period) from 40 sites (n = 110,779, representing 5,485,137 postpartum women) were used to determine whether rates of PPD changed during the first year of the pandemic. Postpartum depressive symptoms were assessed using the Patient Health Questionnaire 2-item. Average marginal effects and contrasts of predictive margins derived from a multivariable logistic regression model were used to compare the risk of PPD before and during the pandemic in the overall sample and across racial/ethnic subgroups. Results: Adjusting for sociodemographic and clinical characteristics, we found that the overall risk for PPD remained stable (0.0 percentage points [pp]; 95% confidence interval [CI]: -0.7, 0.6 pp) in the first year of the pandemic. We detected no statistically significant changes in risk for PPD across seven of eight racial/ethnic groups considered; however, the risk of PPD among non-Hispanic Black women fell by 2.0 pp (95% CI: -3.5, -0.4 pp) relative to the pre-pandemic period. Conclusion: We identified important subgroup differences in pandemic-related changes in risk for PPD.

An Innovative Design to Enhance Osteoinductive Efficacy and Biomechanical Behavior of a Titanium Dental Implant.

The present study investigated the in vivo bone-forming efficacy of an innovative titanium (Ti) dental implant combined with a collagen sponge containing recombinant human bone morphogenetic protein-2 (BMP-2) in a pig model. Two different concentrations of BMP-2 (20 and 40 µg/mL) were incorporated into collagen sponges and placed at the bottom of Ti dental implants. The investigated implants were inserted into the edentulous ridge at the canine-premolar regions of Lanyu small-ear pigs, which were then euthanized at weeks 1, 2, 4, 8, and 12 post-implantation. Specimens containing the implants and surrounding bone tissue were collected for histological evaluation of their bone-to-implant contact (BIC) ratios and calculation of maximum torques using removal torque measurement. Analytical results showed that the control and BMP-2-loaded implants presented good implant stability and bone healing for all testing durations. After 1 week of healing, the BMP-2-loaded implants with a concentration of 20 µg/mL exhibited the highest BIC ratios, ranging from 58% to 76%, among all groups (p = 0.034). Additionally, they also possessed the highest removal torque values (50.1 ± 1.3 N-cm) throughout the 8-week healing period. The BMP-2-loaded implants not only displayed excellent in vivo biocompatibility but also presented superior osteoinductive performance. Therefore, these findings demonstrate that BMP-2 delivered through a collagen sponge can potentially enhance the early-stage osseointegration of Ti dental implants.

Safety and efficacy of liposomal irinotecan as the second-line treatment for advanced pancreatic cancer: A systematic review and meta-analysis.

INTRODUCTION: The use of nanoliposomal irinotecan (nal-IRI) is a novel regimen for pancreatic cancer, featuring a longer half-life and increased area under the concentration-time curve. However, comprehensive systematic reviews or meta-analyses evaluating its efficacy as a second-line treatment have been scarce. Therefore, this study aims to review the current body of evidence on nal-IRI, assessing its overall clinical performances regarding the disease. METHODS: A systemic literature search was conducted based on articles published before September 26, 2023 in PubMed, Cochrane Library, EMBASE, and Web of Science databases. The fixed effect model was performed to calculate pooled mean difference and odds ratio for essential outcomes, such as overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and adverse events. RESULTS: A total of 21 studies, including 3017 patients with locally advanced unresectable or metastatic pancreatic cancers, were considered eligible. The use of nal-IRI, together with 5-fluorouracil and leucovorin, resulted in significantly improved PFS and OS, with a pooled mean difference of 1.01 months (95% confidence interval (95%CI)=0.97-1.05, p<0.01) and 0.29 months (95% CI=0.18-0.39, p<0.01) respectively; a pooled risk ratio of 2.06 (95%CI=1.30-3.27, p=0.002) for ORR compared to other second-line regimens. Nonetheless, an increased risk of grade 3 or greater neutropenia, anemia, hypokalemia, diarrhea, and vomiting was also noted. CONCLUSION: Nal-IRI-based second-line treatments exhibited significantly improved PFS, OS and ORR compared to other available treatments in advanced pancreatic cancer. Further research is necessary to corroborate these findings and define the role of nal-IRI in both first and later lines of therapy.

Postoperative neurocognitive disorders in ambulatory surgery: a narrative review.

Postoperative neurocognitive disorders (PoNCDs), such as postoperative delirium and cognitive dysfunction or decline can occur after surgery, especially in older patients. This significantly affects patient morbidity and surgical outcomes. Among various risk factors, recent studies have shown that preoperative frailty is associated with developing these conditions. Although the mechanisms underlying PoNCDs remain unclear, neuroinflammation appears to play an important role in their development. For the prevention and treatment of PoNCDs, medication modification, a balanced diet, and prehabilitation and rehabilitation programs have been suggested. The risk of developing PoNCDs is thought to be lower in ambulatory patients. However, owing to technological advancements, an increasing number of older and sicker patients are undergoing more complex surgeries and are often not closely monitored after discharge. Therefore, equal attention should be paid to all patient populations. This article presents an overview of PoNCDs and highlights issues of particular interest for ambulatory surgery.

Assessing the properties of patient-specific treatment effect estimates from causal forest algorithms under essential heterogeneity.

BACKGROUND: Treatment variation from observational data has been used to estimate patient-specific treatment effects. Causal Forest Algorithms (CFAs) developed for this task have unknown properties when treatment effect heterogeneity from unmeasured patient factors influences treatment choice - essential heterogeneity. METHODS: We simulated eleven populations with identical treatment effect distributions based on patient factors. The populations varied in the extent that treatment effect heterogeneity influenced treatment choice. We used the generalized random forest application (CFA-GRF) to estimate patient-specific treatment effects for each population. Average differences between true and estimated effects for patient subsets were evaluated. RESULTS: CFA-GRF performed well across the population when treatment effect heterogeneity did not influence treatment choice. Under essential heterogeneity, however, CFA-GRF yielded treatment effect estimates that reflected true treatment effects only for treated patients and were on average greater than true treatment effects for untreated patients. CONCLUSIONS: Patient-specific estimates produced by CFAs are sensitive to why patients in real-world practice make different treatment choices. Researchers using CFAs should develop conceptual frameworks of treatment choice prior to estimation to guide estimate interpretation ex post.

Use of interrupted time-series analyses in evaluating health economic outcomes following implementation of multilayer water-tight wound closure in a primary total joint arthroplasty population.

Aim: Total joint arthroplasty (TJA) with multi-layer, watertight closure (MLWC) using knotless barbed suture and 2-octyl cyanoacrylate plus polymer mesh tape was compared with conventional closure (CC) using Vicryl™ sutures and staples. Patients & methods: Electronic medical records of patients undergoing TJA (1574: total knee arthroplasty; 580: total hip arthroplasty; 13: unknown) from a single surgeon at a US hospital (CC 2011 to 2013; MLWC 2015 to 2020) were reviewed. Outcomes were length of stay (LOS), discharge to skilled nursing facility (SNF), 90-day surgical site infection (SSI) and 90-day readmission. Logistic regression controlled for baseline characteristics. Adjusted interrupted time series (ITS) analyses accounted for decreasing trends in LOS and SNF discharge over time. Results: Among 2167 TJA cases (mean [standard deviation] age 66.0 [9.7] years, 53.3% female), 906 received CC and 1261 received MLWC. Bivariate analysis showed no statistically significant differences in 90-day SSI rates; however, MLWC patients had 60% lower 90-day readmission rates (1.5 vs 3.8%, p < 0.05), 44% lower LOS (1.4 vs 2.5 days, p < 0.05) and 40% lower discharge rates to a skilled care facility (8.5 vs 14.1%, p < 0.05). Multivariable analyses showed CC patients were 2.45-times more likely to be readmitted within 90 days, 1.88-times more likely to be discharged to SNF and had 1.67-times longer LOS compared with MLWC. ITS analyses showed a sharp decline in LOS (0.9 days) and discharge to SNF (5.6% incidence) after implementation of MLWC, followed by no further changes for the remainder of the study period. Conclusion: MLWC was associated with ≥40% reduction in 90-day readmission, LOS and SNF discharge compared with TJA CC. LOS and discharge rate to SNF declined sharply after the implementation of MLWC.

Validation of biomarkers of aging.

The search for biomarkers that quantify biological aging (particularly 'omic'-based biomarkers) has intensified in recent years. Such biomarkers could predict aging-related outcomes and could serve as surrogate endpoints for the evaluation of interventions promoting healthy aging and longevity. However, no consensus exists on how biomarkers of aging should be validated before their translation to the clinic. Here, we review current efforts to evaluate the predictive validity of omic biomarkers of aging in population studies, discuss challenges in comparability and generalizability and provide recommendations to facilitate future validation of biomarkers of aging. Finally, we discuss how systematic validation can accelerate clinical translation of biomarkers of aging and their use in gerotherapeutic clinical trials.

The impact of sodium-glucose cotransporter-2 inhibitors on outcome of patients with diabetes mellitus and colorectal cancer.

BACKGROUND AND AIM: Patients with type 2 diabetes mellitus (T2DM) have a higher risk of colorectal cancer (CRC), and those with diagnosed CRC have a poorer prognosis compared with individuals with normal glucose levels. The inhibition of sodium-glucose cotransporter 2 (SGLT2) channels has been associated with a reduction in tumor proliferation in preclinical studies. We aimed to investigate the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the outcome of T2DM patients with colorectal cancer. METHODS: We performed a retrospective cohort study comprising adult patients with T2DM and colorectal adenocarcinoma. SGLT2i recipients were matched to non-SGLT2i recipients in a 1:1 ratio based on age, sex, and cancer stage. The primary outcome was overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were previously reported serious adverse events associated with SGLT2i. RESULTS: We identified 1347 patients with T2DM and colorectal adenocarcinoma, from which 92 patients in the SGLT2i cohort were matched to the non-SGLT2i cohort. Compared to non-SGLT2i recipients, SGLT2i recipients had a higher rate of 5-year OS (86.2% [95% CI: 72.0-93.5] vs 62.3% [95% CI: 50.9-71.8], P = 0.013) and 5-year PFS (76.6% [95% CI: 60.7-86.7] vs 57.0% [95% CI: 46.2-66.4], P = 0.021). In Cox proportional hazard analyses, SGLT2i were associated with a 50-70% reduction in all-cause mortality and disease progression. SGLT2i were not associated with an increased risk of serious adverse events. CONCLUSION: SGLT2i were associated with a higher rate of survival in T2DM patients with colorectal cancer.

Smoking Dependence, Time-Discounting, and Sustained Cessation Behavior: A Longitudinal Study of Predominantly Light Smokers.

INTRODUCTION: This study aimed to assess whether two established psychosocial predictors of smoking abstinence, nicotine dependence and time-discounting, also apply to a population of predominantly cigarette light smokers, which is the dominant pattern of smoking in countries like Mexico. Relatively infrequent smoking is increasingly prevalent, yet still harmful, making it important to understand the predictors of cessation in this population. AIMS AND METHODS: Mexican adult smokers recruited from an online consumer panel were surveyed every 4 months between November 2018 and July 2020. We considered respondents who reported a quit attempt in between surveys (n = 1288). Dependence was measured with a 10-item version of the Wisconsin Inventory of Smoking Dependence Motives (WISDM). Time-discounting was assessed with five branching questions about hypothetical reward scenarios. Logistic models regressed sustained quit attempts (≥30 days of abstinence) at time t + 1 on study variables at time t. RESULTS: We found strong interitem reliability (α = 0.92) and intraindividual consistency of our brief WISDM (ρ = 0.68), but moderate intraindividual consistency of the time-discounting measure (ρ = 0.48). Forty-eight percent of the sample reported sustained quit attempts, and 79% were non-daily or light daily smokers (≤5 cigarettes per day). Smokers with higher WISDM-10 had lower odds of sustained quitting and this result remained when controlling for smoking frequency and the Heaviness of Smoking Index (adjusted odds ratio [AOR] = 0.768). Time-discounting was unassociated with sustained quitting. CONCLUSIONS: Our findings suggest that a brief, 10-item multidimensional measure of dependence is useful for predicting sustained quitting in a context of relatively light smoking; time-discounting appears less relevant, although our results are not conclusive because of the low test-retest reliability of our measure. IMPLICATIONS: Given the increase in non-daily and light daily cigarette smoking in many countries, including in Mexico, and the health risks this still poses, it is important to understand the predictors of cessation among relatively light smokers. The WISDM-10 multidimensional measure seems to be a good instrument to assess dependence and predict successful quitting in this population, and possibly more appropriate than physical dependence measures. As such, it could help design and target more suitable cessation treatments for non-daily and daily light cigarette smokers. While this study did not find time-discounting to be a relevant predictor of smoking abstinence, future studies should explore other measures.

Classification of radial polydactyly based on physical characteristics.

BACKGROUND: Previous classifications in polydactyly of the thumb were by the level of duplication on radiography. This study aimed to develop a practical algorithm based on physical characteristics for treatment guidelines. METHODS: The polydactylies were stratified using four physical characteristics: floating, symmetry, dominant side, and joint angulation/nail size. The algorithm identified the hypoplastic type and then stratified the polydactylies as symmetric and asymmetric. The asymmetric type was divided into ulnar dominant and radial dominant. The symmetric type was divided into adequate type and inadequate type. The prediction of treatments was studied retrospectively by the distribution of surgical procedures in 500 patients with 545 affected thumbs, by the new classification and the Wassel-Flatt classification. RESULTS: Of the 545 polydactylies, 78 (14.5%) were categorized as the hypoplastic type, 369 (67.5%) as the ulnar-dominant type, 8 (1.5%) as the radial-dominant type, 70 (12.8%) as the symmetric adequate nail type, and 20 (3.7%) as the symmetric inadequate type. Treatments were excision and reconstruction in 403 polydactylies (73.9%), simple excision in 135 polydactylies (24.8%), and the Bilhaut-Cloquet procedure, ray amputation, and on-top plasty procedures were only performed in 7 polydactylies (1.3%). The distribution of surgical procedures was distinct among the new classification types and was similar among the Wassel-Flatt types. CONCLUSIONS: The new classification stratified polydactylies by physical findings in a stepwise manner. Though surgical technical details are not included, this simple classification is useful for paediatricians and parents to understand how a surgical decision is made. LEVEL OF EVIDENCE: Diagnostic Level IV.

Evaluating the Impact of CenteringPregnancy Program Versus Individual Prenatal Care on Gestational Weight Gain.

Introduction: The CenteringPregnancy (CP) program-proven to reduce preterm births-was modified to achieve more optimal gestational weight gain (GWG) by an intentional incorporation of nutrition education. We compared the effect of the modified CP program versus individual prenatal care (IPNC) on GWG. Methods: This observational study used linked birth certificate data and hospital discharge records of women who received prenatal care (PNC) in South Carolina Midlands' obstetric clinics between 2015 and 2019. Linear and multinomial logistic regressions were used to compare participants in CP (n = 568) versus IPNC on weight gain, measured by total GWG (delivery weight minus prepregnancy weight), weekly rate of weight gain, and meeting the Institute of Medicine's recommendations (inadequate, adequate, and excessive GWG). Nonrandom assignment to program was controlled by propensity scoring. Results: CP participants differed from IPNC participants in race, nulliparous, education, and type of health insurance, but not in parity or month PNC began (p-Value <0.05). CP and IPNC participants had a similar GWG experience: total GWG (coef(ß) = -0.054; 95% confidence interval [CI] -0.78 to 0.6), total weekly weight gain (coef(ß) = -0.004; 95% CI -0.03 to 0.03), total GWG category (inadequate GWG: RRR = 0.85, 95% CI 0.64-1.21, and excessive GWG: relative risk ratio (RRR) = 0.92, 95% CI 0.71-1.20 vs. adequate), and weekly weight gain category (inadequate GWG: RRR = 0.73, 95% CI 0.53-1.01, and excessive GWG: RRR = 0.83, 95% CI 0.61-1.13 vs. adequate). Conclusion: The CP program with an enhanced nutritional knowledge component was not associated with achieving recommended GWG. Further investigation is needed to explain the lack of impact.

Rationale, design, and protocol for a hybrid type 1 effectiveness-implementation trial of a proactive smoking cessation electronic visit for scalable delivery via primary care: the E-STOP trial.

BACKGROUND: Cigarette smoking remains the leading cause of preventable disease and death in the United States. Primary care offers an ideal setting to reach adults who smoke cigarettes and improve uptake of evidence-based cessation treatment. Although U.S. Preventive Services Task Force Guidelines recommend the 5As model (Ask, Advise, Assess, Assist, Arrange) in primary care, there are many barriers to its implementation. Automated, comprehensive, and proactive tools are needed to overcome barriers. Our team developed and preliminarily evaluated a proactive electronic visit (e-visit) delivered via the Electronic Health Record patient portal to facilitate evidence-based smoking cessation treatment uptake in primary care, with promising initial feasibility and efficacy. This paper describes the rationale, design, and protocol for an ongoing Hybrid Type I effectiveness-implementation trial that will simultaneously assess effectiveness of the e-visit intervention for smoking cessation as well as implementation potential across diverse primary care settings. METHODS: The primary aim of this remote five-year study is to examine the effectiveness of the e-visit intervention vs. treatment as usual (TAU) for smoking cessation via a clinic-randomized clinical trial. Adults who smoke cigarettes are recruited across 18 primary care clinics. Clinics are stratified based on their number of primary care providers and randomized 2:1 to either e-visit or TAU. An initial baseline e-visit gathers information about patient smoking history and motivation to quit, and a clinical decision support algorithm determines the best evidence-based cessation treatment to prescribe. E-visit recommendations are evaluated by a patient's own provider, and a one-month follow-up e-visit assesses cessation progress. Main outcomes include: (1) cessation treatment utilization (medication, psychosocial cessation counseling), (2) reduction in cigarettes per day, and (3) biochemically verified 7-day point prevalence abstinence (PPA) at six-months. We hypothesize that patients randomized to the e-visit condition will have better cessation outcomes (vs. TAU). A secondary aim evaluates e-visit implementation potential at patient, provider, and organizational levels using a mixed-methods approach. Implementation outcomes include acceptability, adoption, fidelity, implementation cost, penetration, and sustainability. DISCUSSION: This asynchronous, proactive e-visit intervention could provide substantial benefits for patients, providers, and primary care practices and has potential to widely improve reach of evidence-based cessation treatment. TRIAL REGISTRATION: NCT05493254.

The Efficacy of Cationic Amphiphilic Antihistamines on Outcomes of Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Cationic amphiphilic H1-antihistamines have demonstrated antitumor effects in preclinical studies. We conducted a retrospective cohort study to investigate their impact on patients with pancreatic adenocarcinoma (PDAC). METHODS: We performed a matched cohort study involving PDAC patients from two tertiary centers in Taiwan using criteria including age, sex, and cancer stage. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and objective response rates (ORR). RESULTS: We matched 28 cationic amphiphilic antihistamine users with 56 non-cationic amphiphilic antihistamine users. Cationic amphiphilic antihistamine users showed significantly longer OS (median 16.4 [IQR, 2.8 - 89.0] vs.5.8 [IQR, 2.0 - 9.8] months; p<0.001) and PFS (median 12.2 [IQR, 2.2 - 83.3] vs. 5.2 [IQR, 1.7 - 8.4] months; p=0.002) compared to non-users. In the Cox proportional hazard models, the use of cationic amphiphilic antihistamines was associated with approximately 60% lower risk of all-cause mortality and disease progression. Additionally, cationic amphiphilic antihistamine users exhibited a significantly greater ORR than non-users (39% vs. 7%, p=0.004). CONCLUSION: Our study suggests that cationic amphiphilic antihistamines are associated with improved survival outcomes in PDAC patients.

The long-term effects of aggressive spasticity reducing treatment, including selective dorsal rhizotomy, on joint kinematic outcomes of persons with cerebral palsy.

BACKGROUND: Selective dorsal rhizotomy (SDR) creates a large and permanent reduction of spasticity for children with cerebral palsy (CP). Previous SDR outcomes studies have generally lacked appropriate control groups, had limited sample sizes, or reported short-term follow-up, limiting evidence for improvement in long-term gait function. RESEARCH QUESTION: Does aggressive spasticity management for individuals with CP improve long-term gait kinematics (discrete joint kinematics) compared to a control group of individuals with CP with minimal spasticity management? METHODS: This study was a secondary analysis - focused on joint-level kinematics - of a previous study evaluating the long-term outcomes of SDR. Two groups of participants were recruited based on a retrospectively completed baseline clinical gait study. One group received aggressive spasticity treatment including a selective dorsal rhizotomy (Yes-SDR group), while the other group had minimal spasticity management (No-SDR group). Both groups had orthopedic surgery treatment. Groups were matched on baseline spasticity. All participants prospectively returned for a follow-up gait study in young adulthood (greater than 21 years of age and at least 10 years after baseline). Change scores in discrete kinematic variables from baseline to follow-up were assessed using a linear model that included treatment arm (Yes-SDR, No-SDR), baseline age, and baseline kinematic value. For treatment arm, 5° and 5 Gait Deviation Index points were selected as thresholds to be considered a meaningful difference between treatment groups. RESULTS: At follow-up, there were no meaningful differences in pelvis, hip, knee, or ankle kinematic variable changes between treatment arms. Max knee flexion - swing showed a moderate treatment effect for Yes-SDR, although it did not reach the defined threshold. SIGNIFICANCE: Aggressive spasticity treatment does not result in meaningful differences in gait kinematics for persons with cerebral palsy in young adulthood compared to minimal spasticity management with both groups having orthopedic surgery.