The Parent PrU: A measure to assess personal utility of pediatric genomic results.

PURPOSE: We aimed to adapt and validate an existing patient-reported outcome measure, the personal-utility (PrU) scale, for use in the pediatric genomic context. METHODS: We adapted the adult version of the PrU and obtained feedback from 6 parents whose child had undergone sequencing. The resulting measure, the Parent PrU, was administered to parents of children in 4 pediatric cohorts of the Clinical Sequencing Evidence-Generating Research consortium after they received their children's genomic results. We investigated the measure's structural validity and internal consistency. RESULTS: We conducted a principal-axis factor analysis with oblimin rotation on data from 755 participants to determine structural validity. These analyses yielded a 3-factor solution, accounting for 76% of the variance in the 16 items. We used Cronbach's α to assess the internal consistency of each factor: (1) child benefits (α = .95), (2) affective parent benefits (α = .90), and (3) parent control (α = .94). CONCLUSION: Our evidence suggests that the Parent PrU scale has potential as a measure for assessing parent-reported personal utility of their children's genomic results. Additional research is needed to further validate the Parent PrU scale, including by comparing its findings with utility assessments reported by clinicians and children themselves.

Pregnancy and weaning regulate human maternal liver size and function.

During pregnancy, the rodent liver undergoes hepatocyte proliferation and increases in size, followed by weaning-induced involution via hepatocyte cell death and stromal remodeling, creating a prometastatic niche. These data suggest a mechanism for increased liver metastasis in breast cancer patients with recent childbirth. It is unknown whether the human liver changes in size and function during pregnancy and weaning. In this study, abdominal imaging was obtained in healthy women at early and late pregnancy and postwean. During pregnancy time points, glucose production and utilization and circulating bile acids were measured. Independently of weight gain, most women's livers increased in size with pregnancy, then returned to baseline postwean. Putative roles for bile acids in liver growth and regression were observed. Together, the data support the hypothesis that the human liver is regulated by reproductive state with growth during pregnancy and volume loss postwean. These findings have implications for sex-specific liver diseases and for breast cancer outcomes.

The PrU: Development and validation of a measure to assess personal utility of genomic results.

PURPOSE: People report experiencing value from learning genomic results even in the absence of clinically actionable information. Such personal utility has emerged as a key concept in genomic medicine. The lack of a validated patient-reported outcome measure of personal utility has impeded the ability to assess this concept among those receiving genomic results and evaluate the patient-perceived value of genomics. We aimed to construct and psychometrically evaluate a scale to measure personal utility of genomic results-the Personal Utility (PrU) scale. METHODS: We used an evidence-based, operational definition of personal utility, with data from a systematic literature review and Delphi survey to build a novel scale. After piloting with 24 adults, the PrU was administered to healthy adults in a Clinical Sequencing Evidence-Generating Research Consortium study after receiving results. We investigated the responses using exploratory factor analysis. RESULTS: The exploratory factor analysis (N = 841 participants) resulted in a 3-factor solution, accounting for 74% of the variance in items: (1) self-knowledge (α = 0.92), (2) reproductive planning (α = 0.89), and (3) practical benefits (α = 0.91). CONCLUSION: Our findings support the use of the 3-factor PrU to assess personal utility of genomic results. Validation of the PrU in other samples will be important for more wide-spread application.

Most people share genetic test results with relatives even if the findings are normal: Family communication in a diverse population.

PURPOSE: With increasing utilization of genetic testing, sharing genetic information can become part of general family health communication while providing biological relatives with important information about their own genetic risk. Importantly, little is known about motivations for and barriers to family communication of genetic information in historically underserved populations. METHODS: Using mixed methods, we explored patient experiences with family communication in a study population of English- and Spanish-speaking adults aged 18 to 49 years, enriched for participants from historically underserved backgrounds. Risk screening for hereditary cancer guided genetic testing for cancer risk genes and other medically actionable findings. RESULTS: Most participants overall (91%), including most with normal findings (89%), shared or planned to share their results with relatives. Common motivations for sharing results were to give relatives information about their genetic risk and because the participant thought the results were interesting. Reasons for not sharing were limited contact with relatives, perceptions of limited clinical utility for relatives, and concern that discussion of genetic information was stigmatized or taboo. CONCLUSION: Results demonstrate high rates of sharing genetic information, indicate motivations for sharing go beyond facilitating genetic testing for relatives, and suggest general willingness to share genetic information as part of family health communication.

Medical interpreter-mediated genetic counseling for Spanish preferring adults at risk for a hereditary cancer syndrome.

The objective of this study was to identify interpretation challenges specific to exome sequencing and errors of potential clinical significance in the context of genetic counseling for adults at risk for a hereditary cancer syndrome. Thirty transcripts of interpreter-mediated telephone results disclosure genetic counseling appointments were coded for errors by bilingual researchers, and the coders applied an overall rating to denote the degree to which the errors interfered with communication overall. Genetic counselors reviewed a subset of errors flagged for potential clinical significance to identify those likely to have clinical impact. Qualitative interviews with 19 interpreters were analyzed to elucidate the challenges they face in interpreting for genetic counseling appointments. Our analysis identified common interpretation errors such as raising the register, omissions, and additions. Further, we found errors specific to genetic counseling concepts and content that appeared to impact the ability of the genetic counselor to accurately assess risk. These errors also may have impacted the patient's ability to understand their results, access appropriate follow-up care, and communicate with family members. Among interpreters' strengths was the use of requests for clarification; in fact, even more use of clarification would have been beneficial in these encounters. Qualitative interviews surfaced challenges stemming from the structure of interpreter work, such as switching from medical and nonmedical interpretations without substantial breaks. Importantly, while errors were frequent, most did not impede communication overall, and most were not likely to impact clinical care. Nevertheless, potentially clinically impactful errors in communication of genetics concepts may contribute to inequitable care for limited English proficient patients and suggest that additional training in genetics and specialization in healthcare may be warranted. In addition, training for genetic counselors and guidance for patients in working effectively with interpreters could enhance interpreters' transmission of complex genetic concepts.

A Primary Care-Based Cognitive Behavioral Therapy Intervention for Long-Term Opioid Users With Chronic Pain : A Randomized Pragmatic Trial.

BACKGROUND: Chronic pain is common, disabling, and costly. Few clinical trials have examined cognitive behavioral therapy (CBT) interventions embedded in primary care settings to improve chronic pain among those receiving long-term opioid therapy. OBJECTIVE: To determine the effectiveness of a group-based CBT intervention for chronic pain. DESIGN: Pragmatic, cluster randomized controlled trial. (ClinicalTrials.gov: NCT02113592). SETTING: Kaiser Permanente health care systems in Georgia, Hawaii, and the Northwest. PARTICIPANTS: Adults (aged ≥18 years) with mixed chronic pain conditions receiving long-term opioid therapy. INTERVENTION: A CBT intervention teaching pain self-management skills in 12 weekly, 90-minute groups delivered by an interdisciplinary team (behaviorist, nurse, physical therapist, and pharmacist) versus usual care. MEASUREMENTS: Self-reported pain impact (primary outcome, as measured by the PEGS scale [pain intensity and interference with enjoyment of life, general activity, and sleep]) was assessed quarterly over 12 months. Pain-related disability, satisfaction with care, and opioid and benzodiazepine use based on electronic health care data were secondary outcomes. RESULTS: A total of 850 patients participated, representing 106 clusters of primary care providers (mean age, 60.3 years; 67.4% women); 816 (96.0%) completed follow-up assessments. Intervention patients sustained larger reductions on all self-reported outcomes from baseline to 12-month follow-up; the change in PEGS score was -0.434 point (95% CI, -0.690 to -0.178 point) for pain impact, and the change in pain-related disability was -0.060 point (CI, -0.084 to -0.035 point). At 6 months, intervention patients reported higher satisfaction with primary care (difference, 0.230 point [CI, 0.053 to 0.406 point]) and pain services (difference, 0.336 point [CI, 0.129 to 0.543 point]). Benzodiazepine use decreased more in the intervention group (absolute risk difference, -0.055 [CI, -0.099 to -0.011]), but opioid use did not differ significantly between groups. LIMITATION: The inclusion of only patients with insurance in large integrated health care systems limited generalizability, and the clinical effect of change in scores is unclear. CONCLUSION: Primary care-based CBT, using frontline clinicians, produced modest but sustained reductions in measures of pain and pain-related disability compared with usual care but did not reduce use of opioid medication. PRIMARY FUNDING SOURCE: National Institutes of Health.

ORCA, a values-based decision aid for selecting additional findings from genomic sequencing in adults: Efficacy results from a randomized trial.

PURPOSE: Individuals having genomic sequencing can choose to be notified about pathogenic variants in genes unrelated to the testing indication. A decision aid can facilitate weighing one's values before making a choice about these additional results. METHODS: We conducted a randomized trial (N = 231) comparing informed values-choice congruence among adults at risk for a hereditary cancer syndrome who viewed either the Optional Results Choice Aid (ORCA) or web-based additional findings information alone. ORCA is values-focused with a low-literacy design. RESULTS: Individuals in both arms had informed values-choice congruence (75% and 73% in the decision aid and web-based groups, respectively; odds ratio [OR] = 1.10, 95% CI = 0.58-2.08). Most participants had adequate knowledge (79% and 76% in the decision aid and web-based groups, respectively; OR = 1.20, 95% CI = 0.61-2.34), with no significant difference between groups. Most had information-seeking values (97% and 98% in the decision aid and web-based groups, respectively; OR = 0.59, 95% CI = 0.10-3.61) and chose to receive additional findings. CONCLUSION: The ORCA decision aid did not significantly improve informed values-choice congruence over web-based information in this cohort of adults deciding about genomic results. Both web-based approaches may be effective for adults to decide about receiving medically actionable additional results.

Laboratory-related outcomes from integrating an accessible delivery model for hereditary cancer risk assessment and genetic testing in populations with barriers to access.

PURPOSE: This study aimed to evaluate the laboratory-related outcomes of participants who were offered genomic testing based on cancer family history risk assessment tools. METHODS: Patients from clinics that serve populations with access barriers, who are screened at risk for a hereditary cancer syndrome based on adapted family history collection tools (the Breast Cancer Genetics Referral Screening Tool and PREMM5), were offered exome-based panel testing for cancer risk and medically actionable secondary findings. We used descriptive statistics, electronic health record review, and inferential statistics to explore participant characteristics and results, consultations and actions related to pathogenic/likely pathogenic variants identified, and variables predicting category of findings, respectively. RESULTS: Of all the participants, 87% successfully returned a saliva kit. Overall, 5% had a pathogenic/likely pathogenic cancer risk variant and 1% had a secondary finding. Almost all (14/15, 93%) participants completed recommended consultations with nongenetics providers after an average of 17 months. The recommended actions (eg, breast magnetic resonance imaging) were completed by 17 of 25 participants. Participant personal history of cancer and PREMM5 score were each associated with the category of findings (history and colon cancer finding, Fisher's exact P = .02; history and breast cancer finding, Fisher's exact P = .01; PREMM5TM score; and colon cancer finding, Fisher's exact P < .001). CONCLUSION: This accessible model of hereditary cancer risk assessment and genetic testing yielded results that were often acted upon by patients and physicians.

An accessible, relational, inclusive, and actionable (ARIA) model of genetic counseling compared with usual care: Results of a randomized controlled trial.

PURPOSE: Effective approaches to communicate genomic information are needed to ensure equitable care. In a randomized controlled superiority trial, we tested a novel practice model that aims to make genetic counseling inclusive, by making the communication accessible, relational, and actionable (ARIA). METHODS: In total, 696 English- and Spanish-speaking patients aged 18 to 49 years, enriched for individuals from historically underserved backgrounds, were randomized in 1:1 ratio to ARIA or usual care. Primary outcomes were accuracy of recall, communication satisfaction, and perceived understanding. In total, 33 participants completed qualitative interviews. RESULTS: Recall and understanding were high for all participants. ARIA participants scored higher on the relationship scale of communication satisfaction (mean difference = 0.09, 95% CI = <0.01 to 0.17). Moderator analyses of communication satisfaction showed that those with lower health literacy reported less communication difficulty in ARIA and those using medical interpreters reported greater communication ease in ARIA. No significant difference was found on other primary and secondary outcomes. Qualitative data enhanced understanding of how and why ARIA can be effective. CONCLUSION: This study provides evidence that a genetic counseling intervention that focuses on specific communication skills to enhance relationship-building, patient engagement, and comprehension can be effective with all patients and may be especially valuable for patients of lower health literacy and Spanish-speakers who use a medical interpreter.

Economic Evaluation: A Randomized Pragmatic Trial of a Primary Care-based Cognitive Behavioral Intervention for Adults Receiving Long-term Opioids for Chronic Pain.

BACKGROUND: Chronic pain is prevalent and costly; cost-effective nonpharmacological approaches that reduce pain and improve patient functioning are needed. OBJECTIVE: Report the incremental cost-effectiveness ratio (ICER), compared with usual care, of cognitive behavioral therapy aimed at improving functioning and pain among patients with chronic pain on long-term opioid treatment. DESIGN: Economic evaluation conducted alongside a pragmatic cluster randomized trial. SUBJECTS: Adults with chronic pain on long-term opioid treatment (N=814). INTERVENTION: A cognitive behavioral therapy intervention teaching pain self-management skills in 12 weekly, 90-minute groups delivered by an interdisciplinary team (behaviorists, nurses) with additional support from physical therapists, and pharmacists. OUTCOME MEASURES: Cost per quality adjusted life year (QALY) gained, and cost per additional responder (≥30% improvement on standard scale assessment of Pain, Enjoyment, General Activity, and Sleep). Costs were estimated as-delivered, and replication. RESULTS: Per patient intervention replication costs were $2145 ($2574 as-delivered). Those costs were completely offset by lower medical care costs; inclusive of the intervention, total medical care over follow-up was $1841 lower for intervention patients. Intervention group patients also had greater QALY and responder gains than did controls. Supplemental analyses using pain-related medical care costs revealed ICERs of $35,000, and $53,000 per QALY (for replication, and as-delivered intervention costs, respectively); the ICER when excluding patients with outlier follow-up costs was $106,000. LIMITATIONS: Limited to 1-year follow-up; identification of pain-related utilization potentially incomplete. CONCLUSION: The intervention was the optimal choice at commonly accepted levels of willingness-to-pay for QALY gains; this finding was robust to sensitivity analyses.

Changes in Visceral and Ectopic Adipose Tissue Stores Across Pregnancy and Their Relationship to Gestational Weight Gain.

BACKGROUND: Excessive gestational weight gain has been associated with increased total body fat (TBF), metabolic syndrome, and abdominal obesity. However, little is known about the relationship of gestational weight gain with changes in metabolically active visceral or ectopic (hepatic and skeletal muscle) lipid stores. OBJECTIVES: In a prospective study of 50 healthy, pregnant women, we assessed whether changes in weight were associated with changes in total, visceral, and ectopic lipid stores. METHODS: Participants (ages 19-39) were primarily White (84%). The mean preconception BMI was 25.8 kg/m2 (SD, 4.5 kg/m2; min-max, 17.1-35.9 kg/m2). Measurements were completed at visits 1 and 2 at means of 16 and 34 weeks gestation, respectively, and included TBF using BOD POD; abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) using MRI; and intrahepatic lipids (IHL), intramyocellular lipids (IMCL), and extramyocellular lipids (EMCL) using magnetic resonance spectroscopy. We used paired t-tests to examine changes in adipose tissue and Pearson's correlation to examine associations of adipose tissue changes and weight changes. We also examined whether changes in adipose tissue stores differed by preconception BMI (normal, overweight, and obese), using 1-way ANOVA. RESULTS: The TBF (mean change, +3.5 kg; 95% CI: 2.4-4.6 kg), SAT (mean change, +701 cm3; 95% CI: 421-981 cm3), VAT (mean change, +275 cm3; 95% CI: 170-379 cm3), and IHL (percentage water peak; median, +0.15; IQR = -0.01 to 0.32) values increased significantly; the IMCL and EMCL values did not change. Changes varied by BMI strata, with the least increase (or, for SAT, net loss) among women with obesity. Weight change was positively correlated with changes in TBF (r = 0.83; P < 0.001), SAT (r = 0.74; P < 0.001), and VAT (r = 0.63; P < 0.001) but not significantly correlated with changes in ectopic lipids (IHL, IMCL, and EMCL; -0.14 < r < 0.26). CONCLUSIONS: Preferential deposition of adipose tissue to the viscera in pregnancy, as seen in our sample, could serve an important metabolic function; however, excessive deposition in this region could negatively affect maternal health.

Predicting risk of multiple levels of recurrence and progression after initial diagnosis of nonmuscle-invasive bladder cancer in a multisite, community-based cohort.

BACKGROUND: Nonmuscle-invasive bladder cancer (NMIBC) has heterogeneous recurrence and progression outcomes. Available risk calculators estimate recurrence and progression but do not predict the recurrence stage or grade, which may influence downstream treatment. The objective of this study was to predict risk-stratified NMIBC recurrence and progression based on recurrence tumor classification and grade. METHODS: In total, 2956 patients with NMIBC (

Randomized Controlled Trial of Advance Notification Phone Calls vs Text Messages Prior to Mailed Fecal Test Outreach.

BACKGROUND & AIMS: Mailing fecal immunochemical test (FITs) to individuals who are due for screening (mailed FIT outreach) increases colorectal cancer (CRC) screening. Little is known about how phone-based advance notifications (primers) affect the effectiveness of mailed FIT outreach programs. METHODS: We performed a prospective study of patients at a large urban health center, 50-75 years old and due for screening, with no record of a prior FIT. Participants were randomly assigned to groups that received a live phone call primer (n = 1203) or a text message primer (n = 1622), from June through December 2018. The participants were then mailed a FIT kit, followed by 2 automated calls, and live reminder calls delivered by the care team. The main outcome was completion of FIT within 3 months of assignment to the live phone call or text message group. RESULTS: Participants had a FIT completion rate of 16.8%, a mean age of 58 years, and 80% were Latino. In adjusted intention to treat analyses (n = 2825), FIT completion rates were higher in the patients assigned to receive a live phone call vs text message primer (percentage point difference, 3.3%; 95% CI, 0.4%-6.2%). Between-group differences increased to 7.3% points (95% CI, 3.6%-11.0%) in the per-protocol analysis of 2144 participants reached by the text message (1320/1622, 81%), live call (438/1203, 36%), or voice message (386/1203, 32%). This rate increased to 14.9% points (95% CI; 9.6%-20.1%) in the per-protocol analysis of 1758 participants reached by the text message or reached by the live call. CONCLUSIONS: In a randomized trial, advance notification live phone calls outperformed text messages in prompting health center patients who had not previously completed a FIT to complete a mailed FIT. Clinicaltrials.gov no: NCT03167125.

Improving management of the genitourinary syndrome of menopause: evaluation of a health system-based, cluster-randomized intervention.

BACKGROUND: Genitourinary symptoms are common in postmenopausal women and adversely affect the quality of life. National surveys and data collected from our healthcare system indicate that postmenopausal women with the genitourinary syndrome of menopause often fail to receive appropriate diagnosis or treatment. OBJECTIVE: To promote greater detection and treatment of the genitourinary syndrome of menopause, we created and tested a clinician-focused health system intervention that included clinician education sessions and a suite of evidence-based electronic health record tools. STUDY DESIGN: Using a cluster-randomized design, we allocated primary care (16) and gynecology (6) clinics to the intervention or control group. From September to November 2014, we provided training about the diagnosis and treatment of genitourinary syndrome of menopause in face-to-face presentations at each intervention clinic and in an online video. We developed clinical decision support tools in the electronic health record that contained an evidence-based, point-of-care knowledge resource, a standardized order set, and a checklist of patient education materials for the patient's after visit summary. The tools aimed to facilitate accurate diagnostic coding and prescribing (SmartSet, SmartRx) along with relevant patient information (SmartText). Clinicians who only performed visits at control clinics received no training or notification about the tools. Our primary outcome was vulvovaginal diagnoses made at well visits for women at the age of 55 years and older from November 15, 2014 to November 15, 2015. We also assessed urinary diagnoses, vaginal estrogen prescriptions, and use of the electronic tools. There was departmental support for the intervention but no prioritization within the healthcare system to incentivize change. RESULTS: In the 1-year period, 386 clinicians performed 14,921 well visits for women at the age of 55 years and older. Among the 190 clinicians who performed well visits in the intervention clinics, 109 (57.4%) completed either in-person or online educational training. The proportion of visits that included a vulvovaginal (7.2% vs 5.8%; odds ratio, 1.27; 95% confidence interval, 0.65-2.51) or urinary diagnosis (2.5% vs 3.1%; odds ratio, 0.79; 95% confidence interval, 0.55-1.13) or vaginal estrogen prescription (4.5% vs 3.7%; odds ratio, 1.24; 95% confidence interval, 0.63-2.46) did not differ between study arms. There was a significant interaction for primary care and gynecology, which revealed more vulvovaginal diagnoses by gynecology but not primary care intervention clinics (odds ratio, 1.63; 95% confidence interval, 1.15-2.31), but there was no significant interaction for prescriptions. Clinicians in the intervention clinics were more likely to use decision support tools than those in control clinics-SmartSet (22.2% vs 1.5%; odds ratio, 18.8; 95% confidence interval, 5.5-63.8) and SmartText for patient information (38.0% vs 24.4%; odds ratio, 1.91; 95% confidence interval, 1.10-3.34). A per-protocol analysis revealed similar findings. CONCLUSION: Overall, the intervention did not lead to more diagnoses or prescription therapy for postmenopausal genitourinary symptoms but did result in greater distribution of patient information. Gynecology clinicians were more likely to address genitourinary symptoms generally and were more likely to make a vulvovaginal diagnosis after the intervention. Further efforts for improving care should consider ongoing clinician education beginning with enhanced menopause curricula in residency training. Additional interventions to consider include greater access for postmenopausal women to gynecologic care, addressing treatment barriers, and development of national performance metrics.

Disparities in Elevated Body Mass Index in Youth Receiving Care at Community Health Centers.

Childhood obesity has increased significantly in the United States. Racial subgroups are often grouped into categories in research, limiting our understanding of disparities. This study describes the prevalence of obesity among youth of diverse racial and ethnic backgrounds receiving care at community health centers (CHCs). This cross-sectional study describes the prevalence of elevated body mass index (BMI) (≥85th percentile) and obesity (≥95th percentile) in youth aged 9 to 19 years receiving care in CHCs in 2014. Multilevel logistic regression estimated the prevalence of elevated BMI and obesity by age, race/ethnicity, and sex. Among 64 925 youth, 40% had elevated BMI and 22% were obese. By race, obesity was lowest in the combined Asian/Pacific Islander category (13%); however, when subgroups were separated, the highest prevalence was among Native Hawaiians (33%) and Other Pacific Islanders (42%) and the lowest in Asians. By sex, Black females and Hispanic and Asian males were more likely to be obese. By age, the highest prevalence of obesity was among those aged 9 to 10 years (25%). Youth served by CHCs have a high prevalence of obesity, with significant differences observed by race, sex, and age. Combining race categories obscures disparities. The heterogeneity of communities warrants research that describes different populations to address obesity.

Decision Regret Related to Urinary Diversion Choice among Patients Treated with Cystectomy.

PURPOSE: Patients who undergo cystectomy due to bladder cancer can elect an ileal conduit or a neobladder for urinary diversion. Decision regret related to this choice is an important and undesirable patient reported outcome. Our objective was to compare the severity of decision regret experienced by patients with a neobladder vs an ileal conduit. MATERIALS AND METHODS: We analyzed data from a longitudinal cohort study of patients who underwent cystectomy from 2013 to 2015. We applied multivariable linear regression to examine associations of the urinary diversion method (neobladder vs ileal conduit) with decision regret measured with the DRS (Decision Regret Scale) 6 and 18 months after cystectomy. Covariates included demographic and clinical characteristics, health care utilization and complications after cystectomy, quality of life and factors related to the decision making process, including informed and shared decision making, and goal concordance. RESULTS: Of the 192 patients in our cohort 141 received an ileal conduit and 51 received a neobladder. We observed no significant difference in the DRS score in patients with a neobladder vs an ileal conduit at 6 or 18 months (b=-1.28, 95% CI -9.07-6.53, vs b=-1.55, 95% CI -12.48-9.38). However, informed decision making was negatively related to decision regret at 6 and 18 months (b=-13.08, 95% CI -17.05--9.11, and b=-8.54, 95% CI -4.26--2.63, respectively). Quality of life was negatively associated with decision regret at 18 months (b=-5.50, 95% CI -8.95--2.03). CONCLUSIONS: Patients treated with cystectomy who were more informed about bladder reconstruction options experienced less regret independent of the method selected. Efforts to inform and prepare patients for the bladder reconstruction decision may help prevent decision regret.

The effect of multiple recruitment contacts on response rates and patterns of missing data in a survey of bladder cancer survivors 6 months after cystectomy.

PURPOSE: The Bladder Cancer Quality of Life Study collected detailed and sensitive patient-reported outcomes from bladder cancer survivors in the period after bladder removal surgery, when participation in survey research may present a burden. This paper describes the study recruitment methods and examines the response rates and patterns of missing data. METHODS: Detailed surveys focusing on quality of life, healthcare decision-making, and healthcare expenses were mailed to patients 5-7 months after cystectomy. We conducted up to 10 follow-up recruitment calls. We analyzed survey completion rates following each contact in relation to demographic and clinical characteristics, and patterns of missing data across survey content areas. RESULTS: The overall response rate was 71% (n = 269/379). This was consistent across patient clinical characteristics; response rates were significantly higher among patients over age 70 and significantly lower among racial and ethnic minority patients compared to non-Hispanic white patients. Each follow-up contact resulted in marginal survey completion rates of at least 10%. Rates of missing data were low across most content areas, even for potentially sensitive questions. Rates of missing data differed significantly by sex, age, and race/ethnicity. CONCLUSIONS: Despite the effort required to participate in research, this population of cancer survivors showed willingness to share detailed information about quality of life, health care decision-making, and expenses, soon after major cancer surgery. Additional contacts were effective at increasing participation. Response patterns differed by race/ethnicity and other demographic factors. Our data collection methods show that it is feasible to gather detailed patient-reported outcomes during this challenging period.

Performance of ACMG-AMP Variant-Interpretation Guidelines among Nine Laboratories in the Clinical Sequencing Exploratory Research Consortium.

Evaluating the pathogenicity of a variant is challenging given the plethora of types of genetic evidence that laboratories consider. Deciding how to weigh each type of evidence is difficult, and standards have been needed. In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published guidelines for the assessment of variants in genes associated with Mendelian diseases. Nine molecular diagnostic laboratories involved in the Clinical Sequencing Exploratory Research (CSER) consortium piloted these guidelines on 99 variants spanning all categories (pathogenic, likely pathogenic, uncertain significance, likely benign, and benign). Nine variants were distributed to all laboratories, and the remaining 90 were evaluated by three laboratories. The laboratories classified each variant by using both the laboratory's own method and the ACMG-AMP criteria. The agreement between the two methods used within laboratories was high (K-alpha = 0.91) with 79% concordance. However, there was only 34% concordance for either classification system across laboratories. After consensus discussions and detailed review of the ACMG-AMP criteria, concordance increased to 71%. Causes of initial discordance in ACMG-AMP classifications were identified, and recommendations on clarification and increased specification of the ACMG-AMP criteria were made. In summary, although an initial pilot of the ACMG-AMP guidelines did not lead to increased concordance in variant interpretation, comparing variant interpretations to identify differences and having a common framework to facilitate resolution of those differences were beneficial for improving agreement, allowing iterative movement toward increased reporting consistency for variants in genes associated with monogenic disease.

Development of a Goal Elicitation Measure to Support Choice about Urinary Diversion by Patients with Bladder Cancer.

PURPOSE: Patient centered care aims to align treatment with patient goals, especially when treatment options have equivalent clinical outcomes. For surgeries with lasting impacts that alignment is critical. To our knowledge no psychometrically tested preference elicitation measures exist to support patients with bladder cancer treated with cystectomy, who can often choose between ileal conduit and neobladder diversions. In this study we created a scale to measure how patient goals align with each type of urinary diversion and the associated surgical outcomes. MATERIALS AND METHODS: We performed formative research through focus groups and clinician outreach to adapt a goal dissonance measure. We mailed a survey to adult Kaiser Permanente® members who underwent cystectomy for bladder cancer between January 2013 and June 2015. Eligible patients were identified through electronic health records and chart review. Surveys were mailed 5 to 7 months postoperatively. We administered our 10-item decision dissonance scale along with other decision making measures. We explored goal alignment as well as dissonance. Psychometric analysis included factor analysis, evaluation of scale scores between surgery groups and evaluation with other decision making scores. RESULTS: We identified 10 goals associated with ileal conduit or neobladder diversion. Using survey data on 215 patients our scale differentiated patient goals associated with each diversion choice. On average patients with a neobladder strongly valued neobladder aligned goals such as maintaining body integrity and volitional voiding through the urethra. Patients with an ileal conduit had neutral values on average across all goals. CONCLUSIONS: Our measure lays the foundation for a simple value elicitation approach which could facilitate shared decision making about urinary diversion choice.

The ReThink study: a 3-arm parallel randomized trial of cognitive bias modification, with and without adherence promotion, for adolescent anxiety disorder: trial design and protocol.

BACKGROUND: Anxiety disorders are the most common mental health problem among youth, contribute to reduced quality of daily life, and are associated with high rates of comorbidity. However, treatment rates for anxiety are very low, causing a sizeable treatment gap. There is an immediate need to identify treatment interventions that are effective, affordable, and can be delivered easily to the youth population. Cognitive Bias Modification (CBM) is one potentially effective intervention that could reach youth on a large scale, especially when self-administered at home. Thus, we aim to assess the benefit of CBM to treat youth anxiety. Further, we aim to test whether adding an adherence promotion (AP) component to the CBM intervention can improve outcomes, and whether CBM delivered both with and without the AP component is cost effective. METHODS: This is a 12-month randomized controlled trial (RCT) conducted within an existing healthcare system. Potentially eligible youth (ages 12 to 17) will be identified by reviewing the electronic health record (EHR) for clinical anxiety diagnoses, which are then confirmed via research interview. We aim to enroll 498 participants and randomize them 1:1:1 to one of three arms: Arm 1 is a Low-Ratio version of the CBM program (nearly identical to the other CBM versions, but minimally effective); Arm 2 is a High-Ratio "active" CBM program; and Arm 3 is the High-Ratio CBM program with an added AP component. Participants will complete assessments at baseline, 1-, 3-, 6- and 12-months post-baseline. Youth in all three arms will self-administer the CBM program at home and will be asked to complete twelve intervention sessions over a four-week period. Arm 3 participants (High-Ratio CBM + AP) will also receive up to four telephone calls from phone coaches during the intervention period to provide technical assistance, encouragement, and motivational enhancement to increase adherence. The primary clinical outcome will be anxiety remission at 6-month follow-up. DISCUSSION: This study protocol describes the method and design for an RCT to test whether self-administered CBM both with and without adherence promotion can be an effective at-home treatment for anxious youth. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02156531, First Posted June 5, 2014.