Effects of a change in recall period on reporting severe symptoms: an analysis of a pragmatic multisite trial.

BACKGROUND: Optimal methods for deploying electronic patient-reported outcomes (ePROs) to manage symptoms in routine oncologic practice remain uncertain. The eSyM symptom management program asks chemotherapy and surgery patients to self-report 12 symptoms regularly. Feedback from nurses and patients led to changing the recall period from the past 7 days to the past 24 hours. METHODS: Using questionnaires submitted during the 16-weeks surrounding the recall period change, we assessed the likelihood of reporting a severe, or a moderate-severe, symptom across all 12 symptoms and separately for the 5 most prevalent symptoms. Interrupted time series analyses modeled the effects of the change using generalized linear mixed-effects models. Surgery and chemotherapy cohorts were analyzed separately. Study-wide effects were estimated using a meta-analysis method. RESULTS: In total, 1,692 patients from 6 institutions submitted 7,823 eSyM assessments during the 16-weeks surrounding the recall period change. Shortening the recall period was associated with lower odds of severe symptom reporting in the surgery cohort (OR 0.65; 95% CI 0.46 to 0.93; p = .02) and lower odds of moderate-severe symptom reporting in the chemotherapy cohort (OR 0.83, 95% CI 0.71 to 0.97; p = .02). Among the most prevalent symptoms, 24-hour recall was associated with lower rate of reporting post-operative constipation, but no differences in reporting rates for other symptoms. CONCLUSION: A shorter recall period was associated with a reduction in the proportion of patients reporting moderate-severe symptoms. The optimal recall period may vary depending on whether ePROs are collected for active symptom management, as a clinical trial endpoint, or another purpose. (Clinicaltrails.gov (NCT03850912).

Strategies for Implementing an Electronic Patient-Reported Outcomes-Based Symptom Management Program Across Six Cancer Centers.

Background: Electronic patient-reported outcome (ePRO)-based symptom management improves cancer patients' outcomes. However, implementation of ePROs is challenging, requiring technical resources for integration into clinical systems, substantial buy-in from clinicians and patients, novel workflows to support between-visit symptom management, and institutional investment. Methods: The SIMPRO Research Consortium developed eSyM, an electronic health record-integrated, ePRO-based symptom management program for medical oncology and surgery patients and deployed it at six cancer centers between August 2019 and April 2022 in a type II hybrid effectiveness-implementation cluster randomized stepped-wedge study. Sites documented implementation strategies monthly using REDCap, itemized them using the Expert Recommendations for Implementation Change (ERIC) list and mapped their target barriers using the Consolidated Framework for Implementation Research (CFIR) to inform eSyM program enhancement, facilitate inter-consortium knowledge sharing and guide future deployment efforts. Results: We documented 226 implementation strategies: 35 'foundational' strategies were applied consortium-wide by the coordinating center and 191 other strategies were developed by individual sites. We consolidated these 191 site-developed strategies into 64 unique strategies (i.e., removed duplicates) and classified the remainder as either 'universal', consistently used by multiple sites (N=29), or 'adaptive', used only by individual sites (N=35). Universal strategies were perceived as having the highest impact; they addressed eSyM clinical preparation, training, engagement of patients/clinicians, and program evaluation. Across all documented SIMPRO strategies, 44 of the 73 ERIC strategies were addressed and all 5 CFIR barriers were addressed. Conclusion: Methodical collection of theory-based implementation strategies fostered the identification of universal, high-impact strategies that facilitated adoption of a novel care-delivery intervention by patients, clinicians, and institutions. Attention to the high-impact strategies identified in this project could support implementation of ePROs as a component of routine cancer care at other institutions.

Assessing Patient Readiness for an Electronic Patient-Reported Outcome-Based Symptom Management Intervention in a Multisite Study.

PURPOSE: While the use of electronic patient-reported outcomes (ePROs) in routine clinical practice is increasing, barriers to patient engagement limit adoption. Studies have focused on technology access as a key barrier, yet other characteristics may also confound readiness to use ePROs including patients' confidence in using technology and confidence in asking clinicians questions. METHODS: To assess readiness to use ePROs, adult patients from six US-based health systems who started a new oncology treatment or underwent a cancer-directed surgery were invited to complete a survey that assessed access to and confidence in the use of technology, ease of asking clinicians questions about health, and symptom management self-efficacy. Multivariable ordinal logistic regression models were fit to assess the association between technology confidence, ease of asking questions, and symptom management self-efficacy. RESULTS: We contacted 3,212 individuals, and 1,043 (33%) responded. The median age was 63 years, 68% were female, and 75% reported having access to patient portals. Over 80% had two or more electronic devices. Most patients reported high technology confidence, higher ease of asking clinicians questions, and high symptom management self-efficacy (n = 692; 66%). Patients with high technology confidence also reported higher ease of asking nurses about their health (adjusted odds ratio [AOR], 4.58 [95% CI, 2.36 to 8.87]; P ≤ .001). Those who reported higher ease of asking nurses questions were more likely to report higher confidence in managing symptoms (AOR, 30.54 [95% CI, 12.91 to 72.30]; P ≤ .001). CONCLUSION: Patient readiness to use ePROs likely depends on multiple factors, including technology and communication confidence, and symptom management self-efficacy. Future studies should assess interventions to address these factors.

The Use and Short-term Outcomes of Active Surveillance in Men With National Comprehensive Cancer Network Favorable Intermediate-risk Prostate Cancer: The Initial Michigan Urological Surgery Improvement Collaborative Experience.

PURPOSE: National Comprehensive Cancer Network favorable intermediate-risk prostate cancer is a heterogeneous disease with varied oncologic and survival outcomes. We describe the Michigan Urological Surgery Improvement Collaborative's experience with the use of active surveillance and the short-term oncologic outcomes for men with favorable intermediate-risk prostate cancer.Materials and Methods:We reviewed the Michigan Urological Surgery Improvement Collaborative registry for men diagnosed with favorable intermediate-risk prostate cancer from 2012-2020. The proportion of men with favorable intermediate-risk prostate cancer managed with active surveillance was calculated by year of diagnosis. For men selecting active surveillance, the Kaplan-Meier method was used to estimate treatment-free survival. To assess for the oncologic safety of active surveillance, we compared the proportion of patients with adverse pathology and biochemical recurrence-free survival between men undergoing delayed radical prostatectomy after a period of active surveillance with men undergoing immediate radical prostatectomy. RESULTS: Of the 4,275 men with favorable intermediate-risk prostate cancer, 1,321 (31%) were managed with active surveillance, increasing from 13% in 2012 to 45% in 2020. The 5-year treatment-free probability for men with favorable intermediate-risk prostate cancer on active surveillance was 73% for Gleason Grade Group 1 and 57% for Grade Group 2 disease. More men undergoing a delayed radical prostatectomy had adverse pathology (46%) compared with immediate radical prostatectomy (32%, P < .001), yet short-term biochemical recurrence was similar between groups (log-rank test, P = .131). CONCLUSIONS: The use of active surveillance for men with favorable intermediate-risk prostate cancer has increased markedly. Over half of men with favorable intermediate-risk prostate cancer on active surveillance remained free of treatment 5 years after diagnosis. Most men on active surveillance will not lose their window of cure and have similar short-term oncologic outcomes as men undergoing up-front treatment. Active surveillance is an oncologically safe option for appropriately selected men with favorable intermediate-risk prostate cancer.

The Role of Ca2+ Sparks in Force Frequency Relationships in Guinea Pig Ventricular Myocytes.

Calcium sparks are the elementary Ca2+ release events in excitation-contraction coupling that underlie the Ca2+ transient. The frequency-dependent contractile force generated by cardiac myocytes depends upon the characteristics of the Ca2+ transients. A stochastic computational local control model of a guinea pig ventricular cardiomyocyte was developed, to gain insight into mechanisms of force-frequency relationship (FFR). This required the creation of a new three-state RyR2 model that reproduced the adaptive behavior of RyR2, in which the RyR2 channels transition into a different state when exposed to prolonged elevated subspace [Ca2+]. The model simulations agree with previous experimental and modeling studies on interval-force relations. Unlike previous common pool models, this local control model displayed stable action potential trains at 7 Hz. The duration and the amplitude of the [Ca2+]myo transients increase in pacing rates consistent with the experiments. The [Ca2+]myo transient reaches its peak value at 4 Hz and decreases afterward, consistent with experimental force-frequency curves. The model predicts, in agreement with previous modeling studies of Jafri and co-workers, diastolic sarcoplasmic reticulum, [Ca2+]sr, and RyR2 adaptation increase with the increased stimulation frequency, producing rising, rather than falling, amplitude of the myoplasmic [Ca2+] transients. However, the local control model also suggests that the reduction of the L-type Ca2+ current, with an increase in pacing frequency due to Ca2+-dependent inactivation, also plays a role in the negative slope of the FFR. In the simulations, the peak Ca2+ transient in the FFR correlated with the highest numbers of SR Ca2+ sparks: the larger average amplitudes of those sparks, and the longer duration of the Ca2+ sparks.

Factors Associated with Decision Aid Use in Localized Prostate Cancer.

Purpose: Decision aids have been found to improve patients' knowledge of treatments and decrease decisional regrets. Despite these benefits, there is not widespread use of decision aids for newly diagnosed prostate cancer (PCa). This analysis investigates factors that impact men's choice to use a decision aid for newly diagnosed prostate cancer. Materials and Methods: This is a retrospective analysis of a PCa registry from the Michigan Urological Surgery Improvement Collaborative (MUSIC). We included data from men with newly diagnosed, clinically localized PCa seen from 2018-21 at practices offering a PCa decision aid (Personal Patient Profile-Prostate; P3P). The primary outcome was men's registration to use P3P. We fit a multilevel logistic regression model with patient-level factors and included urologist specific random intercepts. We estimated the intra-class correlation (ICC) and predicted the probability of P3P registration among urologists. Results: A total of 2629 men were seen at practices that participated in P3P and 1174 (45%) registered to use P3P. Forty-one percent of the total variance of P3P registration was attributed to clustering of men under a specific urologist's care. In contrast, only 1.5% of the variance of P3P registration was explained by patient factors. Our model did not include data on socioeconomic, literacy or psychosocial factors, which limits the interpretation of the results. Conclusions: These results suggest that urologists' effect far outweighs patient factors in a man's decision to enroll in P3P. Strategies that encourage providers to increase decision aid adoption in their practices are warranted.

Delivering patient-centered care through shared decision making in overactive bladder.

INTRODUCTION: Men and women living with overactive bladder (OAB) face many treatment decisions as they progress through the treatment pathway. Decisions to pursue specific therapies are highly preference sensitive and ideal for shared decision making (SDM). The aim of this narrative review is to provide urologists with a practical summary of methods to elicit preferences and facilitate SDM to promote patient-centered care for OAB. METHODS: We explore OAB as a preference sensitive condition through a review of treatment outcomes and present available data on prediction tools, patient preferences, and decision aids. We propose a paradigm for applying Everyday SDM to OAB care. RESULTS: Clinical outcome data points to equipoise (balanced outcomes) between options for first-, second-, and third-line OAB therapies, making OAB preference sensitive and appropriate for SDM. Methods to personalize care through individualized outcome prediction calculators and tools to elicit patient preferences are emerging. While patient information about OAB is readily available, we identified few OAB decision aids that facilitate patient preference elicitation and SDM. CONCLUSIONS: OAB is a preference sensitive condition, where treatment is largely based on the patient's preferences and values. SDM is an ideal approach to supporting patients through these treatment decisions. We propose the application of Everyday SDM, a personalized, clinically efficient methodology as a method to support patient-centered OAB care.

Assessing the Impact of Decision Aid Use on Post Prostatectomy Patient Reported Outcomes.

OBJECTIVE: To evaluate whether completing a decision aid, Personal Patient Profile - Prostate (P3P), prior to prostatectomy, affects self-reported bother from post-prostatectomy urinary incontinence and erectile dysfunction. MATERIALS AND METHODS: This retrospective analysis included data from men with newly diagnosed clinically localized, very low to intermediate risk prostate cancer who elected for prostatectomy within the Michigan Urological Surgery Improvement Collaborative between 2018-2021. Multivariable logistic regression models were used to estimate the association between P3P use and bother from post prostatectomy erectile dysfunction and urinary incontinence as measured by the Expanded Prostate Cancer Index Composite (EPIC-26). RESULTS: Among the 3987 patients included, 7% used P3P (n = 266). Men who used P3P reported significantly less bother from erectile dysfunction at 6 months vs non-users (aOR 0.42 [95% CI 0.27-0.66]). At 12 months, the effect of P3P on bother from erectile dysfunction was not statistically significant (aOR 0.62 [95% CI 0.37-1.03]). Men who used P3P did not have a statistically significant difference in bother from urinary incontinence (3-month: aOR 0.56 [95% CI 0.30-1.06]; 6-month; aOR 0.79 [95% CI 0.31-1.97]). CONCLUSION: Within the stated limitations of this study, we find that use of a decision aid for localized prostate cancer was associated with decreased odds of men being bothered from sexual dysfunction but not urinary incontinence at 6 months post prostatectomy.

Pacing Dynamics Determines the Arrhythmogenic Mechanism of the CPVT2-Causing CASQ2G112+5X Mutation in a Guinea Pig Ventricular Myocyte Computational Model.

Calsequestrin Type 2 (CASQ2) is a high-capacity, low-affinity, Ca2+-binding protein expressed in the sarcoplasmic reticulum (SR) of the cardiac myocyte. Mutations in CASQ2 have been linked to the arrhythmia catecholaminergic polymorphic ventricular tachycardia (CPVT2) that occurs with acute emotional stress or exercise can result in sudden cardiac death (SCD). CASQ2G112+5X is a 16 bp (339-354) deletion CASQ2 mutation that prevents the protein expression due to premature stop codon. Understanding the subcellular mechanisms of CPVT2 is experimentally challenging because the occurrence of arrhythmia is rare. To obtain an insight into the characteristics of this rare disease, simulation studies using a local control stochastic computational model of the Guinea pig ventricular myocyte investigated how the mutant CASQ2s may be responsible for the development of an arrhythmogenic episode under the condition of ß-adrenergic stimulation or in the slowing of heart rate afterward once ß-adrenergic stimulation ceases. Adjustment of the computational model parameters based upon recent experiments explore the functional changes caused by the CASQ2 mutation. In the simulation studies under rapid pacing (6 Hz), electromechanically concordant cellular alternans appeared under ß-adrenergic stimulation in the CPVT mutant but not in the wild-type nor in the non-ß-stimulated mutant. Similarly, the simulations of accelerating pacing from slow to rapid and back to the slow pacing did not display alternans but did generate early afterdepolarizations (EADs) during the period of second slow pacing subsequent acceleration of rapid pacing.

Exploiting the Innate Potential of Sorghum/Sorghum-Sudangrass Cover Crops to Improve Soil Microbial Profile That Can Lead to Suppression of Plant-Parasitic Nematodes.

Sorghum/sorghum-sudangrass hybrids (SSgH) have been used as a cover crop to improve soil health by adding soil organic matter, enhancing microbial activities, and suppressing soil-borne pathogens in various cropping systems. A series of SSgH were screened for (1) allelopathic suppression and (2) improvement of soil edaphic factors and soil microbial profile against plant-parasitic nematode (PPNs). The allelopathic potential of SSgH against PPNs is hypothesized to vary by variety and age. In two greenhouse bioassays, 'NX-D-61' sorghum and the 'Latte' SSgH amendment provided the most suppressive allelopathic effect against the female formation of Meloidogyne incognita on mustard green seedlings when using 1-, 2-, or 3-month-old SSgH tissue, though most varieties showed a decrease in allelopathic effect as SSgH mature. A field trial was conducted where seven SSgH varieties were grown for 2.5 months and terminated using a flail mower, and eggplant was planted in a no-till system. Multivariate analysis of measured parameters revealed that increase in soil moisture, microbial biomass, respiration rate, nematode enrichment index, and sorghum biomass were negatively related to the initial abundance of PPNs and the root-gall index at 5 months after planting eggplant in a no-till system. These results suggested that improvement of soil health by SSgH could lead to suppression of PPN infection.

Patient Preferences and Treatment Decisions for Prostate Cancer: Results From A Statewide Urological Quality Improvement Collaborative.

OBJECTIVES: To examine the relationship between influential factors and treatment decisions among men with newly diagnosed prostate cancer (PCa). METHODS: We identified men in the Michigan Urological Surgery Improvement Collaborative registry diagnosed with localized PCa between 2018-2020 who completed Personal Patient Profile-Prostate. We analyzed the proportion of active surveillance (AS) between men who stated future bladder, bowel, and sexual problems (termed influential factors) had "a lot of influence" on their treatment decisions versus other responses. We also assessed the relationship between influential factors, confirmatory testing results and choice of AS. RESULTS: A total of 509 men completed Personal Patient Profile-Prostate. Treatment decisions aligned with influential factors for 88% of men with favorable risk and 49% with unfavorable risk PCa. A higher proportion of men who identified bladder, bowel and sexual concerns as having "a lot of influence" on their treatment decision chose AS, compared with men with other influential factors, although not statistically significant (44% vs 35%, P = .11). Similar results were also found when men were stratified based on PCa risk groups (favorable risk: 78% vs 67%; unfavorable risk: 17% vs 9%, respectively). Despite a small sample size, a higher proportion of men with non-reassuring confirmatory testing selected AS if influential factors had "a lot of influence" compared to "no influence" on their treatment decisions. CONCLUSION: Men's concerns for future bladder, bowel, and sexual function problems, as elicited by a decision aid, may help explain treatment selection that differs from traditional clinical recommendation.

Implementation of prostate cancer treatment decision aid in Michigan: a qualitative study.

BACKGROUND: The American Urological Association White Paper on Implementation of Shared Decision Making (SDM) into Urological Practice suggested SDM represents the state of the art in counseling for patients who are faced with difficult or uncertain medical decisions. The Michigan Urological Surgery Improvement Collaborative (MUSIC) implemented a decision aid, Personal Patient Profile-Prostate (P3P), in 2018 to help newly diagnosed prostate cancer patients make shared decisions with their clinicians. We conducted a qualitative study to assess statewide implementation of P3P throughout MUSIC. METHODS: We recruited urologists and staff from 17 MUSIC practices (8 implementation and 9 comparator practices) to understand how practices engaged patients on treatment discussions and to assess facilitators and barriers to implementing P3P. Interview guides were developed based on the Tailored Interventions for Chronic Disease (TICD) Framework. Interviews were transcribed for analysis and coded independently by two investigators in NVivo, PRO 12. Additionally, quantitative program data were integrated into thematic analyses. RESULTS: We interviewed 15 urologists and 11 staff from 16 practices. Thematic analysis of interview transcripts indicated three key themes including the following: (i) P3P is compatible as a SDM tool as over 80% of implementation urologists asked patients to complete the P3P questionnaire routinely and used P3P reports during treatment discussions; (ii) patient receptivity was demonstrated by 370 (50%) of newly diagnosed patients (n = 737) from 8 practices enrolled in P3P with 78% completion rate, which accounts for 39% of all newly diagnosed patients in these practices; and (iii) urologists' attitudes towards SDM varied. Over a third of urologists stated they did not rely on a decision aid. Comparator practices indicated habit, inertia, or concerns about clinic flow as reasons for not adopting P3P and some were unconvinced a decision aid is needed in their practice. CONCLUSION: Urologists and staff affiliated with MUSIC implementation sites indicated that P3P focuses the treatment discussion on items that are important to patients. Experiences of implementation practices indicate that once initiated, there were no negative effects on clinic flow and urologists indicated P3P saves time during patient counseling, as patients were better prepared for focused discussions. Lack of awareness, personal habits, and inertia are reasons for not implementing P3P among the comparator practices.

Taro Genome Assembly and Linkage Map Reveal QTLs for Resistance to Taro Leaf Blight.

Taro (Colocasia esculenta) is a food staple widely cultivated in the humid tropics of Asia, Africa, Pacific and the Caribbean. One of the greatest threats to taro production is Taro Leaf Blight caused by the oomycete pathogen Phytophthora colocasiae Here we describe a de novo taro genome assembly and use it to analyze sequence data from a Taro Leaf Blight resistant mapping population. The genome was assembled from linked-read sequences (10x Genomics; ∼60x coverage) and gap-filled and scaffolded with contigs assembled from Oxford Nanopore Technology long-reads and linkage map results. The haploid assembly was 2.45 Gb total, with a maximum contig length of 38 Mb and scaffold N50 of 317,420 bp. A comparison of family-level (Araceae) genome features reveals the repeat content of taro to be 82%, >3.5x greater than in great duckweed (Spirodela polyrhiza), 23%. Both genomes recovered a similar percent of Benchmarking Universal Single-copy Orthologs, 80% and 84%, based on a 3,236 gene database for monocot plants. A greater number of nucleotide-binding leucine-rich repeat disease resistance genes were present in genomes of taro than the duckweed, ∼391 vs. ∼70 (∼182 and ∼46 complete). The mapping population data revealed 16 major linkage groups with 520 markers, and 10 quantitative trait loci (QTL) significantly associated with Taro Leaf Blight disease resistance. The genome sequence of taro enhances our understanding of resistance to TLB, and provides markers that may accelerate breeding programs. This genome project may provide a template for developing genomic resources in other understudied plant species.

Phylogenetic Relationships, Breeding Implications, and Cultivation History of Hawaiian Taro (Colocasia Esculenta) Through Genome-Wide SNP Genotyping.

Taro, Colocasia esculenta, is one of the world's oldest root crops and is of particular economic and cultural significance in Hawai'i, where historically more than 150 different landraces were grown. We developed a genome-wide set of more than 2400 high-quality single nucleotide polymorphism (SNP) markers from 70 taro accessions of Hawaiian, South Pacific, Palauan, and mainland Asian origins, with several objectives: 1) uncover the phylogenetic relationships between Hawaiian and other Pacific landraces, 2) shed light on the history of taro cultivation in Hawai'i, and 3) develop a tool to discriminate among Hawaiian and other taros. We found that almost all existing Hawaiian landraces fall into 5 monophyletic groups that are largely consistent with the traditional Hawaiian classification based on morphological characters, for example, leaf shape and petiole color. Genetic diversity was low within these clades but considerably higher between them. Population structure analyses further indicated that the diversification of taro in Hawai'i most likely occurred by a combination of frequent somatic mutation and occasional hybridization. Unexpectedly, the South Pacific accessions were found nested within the clades mainly composed of Hawaiian accessions, rather than paraphyletic to them. This suggests that the origin of clades identified here preceded the colonization of Hawai'i and that early Polynesian settlers brought taro landraces from different clades with them. In the absence of a sequenced genome, this marker set provides a valuable resource towards obtaining a genetic linkage map and to study the genetic basis of phenotypic traits of interest to taro breeding such as disease resistance.