Implementation of Cognitive Behavioral Therapy for psychosis via telehealth: An expert consultation and clinical service model.

Individuals living with psychosis are often underserved in the United States, partly due to the dearth of providers trained in evidence-based practices for this population. One such practice is Cognitive Behavioral Therapy for psychosis, which the Substance Abuse and Mental Health Services Administration has identified as a standard of care for this population. The explosion of telehealth, in large part due to the COVID-19 pandemic, has led to increased opportunities for virtual psychotherapy. Telehealth offers a number of benefits, such as the ability to address service inequities, including lack of access to a local provider well-trained in the modality of therapy needed. The current article describes the National Psychosis Telehealth Program within the National Expert Consultation and Specialized Services (formerly VA National Telemental Health Center) program, U.S. Department of Veterans Affairs. The goal of this telehealth program is to utilize an expert consultation model and offer a remote individual, time-limited Cognitive Behavioral Therapy for psychosis protocol to Veterans across the nation in order to decrease access disparities to this relatively scarce service. We share our initiation activities and lessons learned as we developed this program in hopes of encouraging others to consider similar efforts at their sites. We also include a typical, complex case that serves to illustrate the challenges and benefits of this approach. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Protein NirP1 regulates nitrite reductase and nitrite excretion in cyanobacteria.

When the supply of inorganic carbon is limiting, photosynthetic cyanobacteria excrete nitrite, a toxic intermediate in the ammonia assimilation pathway from nitrate. It has been hypothesized that the excreted nitrite represents excess nitrogen that cannot be further assimilated due to the missing carbon, but the underlying molecular mechanisms are unclear. Here, we identified a protein that interacts with nitrite reductase, regulates nitrogen metabolism and promotes nitrite excretion. The protein, which we named NirP1, is encoded by an unannotated gene that is upregulated under low carbon conditions and controlled by transcription factor NtcA, a central regulator of nitrogen homeostasis. Ectopic overexpression of nirP1 in Synechocystis sp. PCC 6803 resulted in a chlorotic phenotype, delayed growth, severe changes in amino acid pools, and nitrite excretion. Coimmunoprecipitation experiments indicated that NirP1 interacts with nitrite reductase, a central enzyme in the assimilation of ammonia from nitrate/nitrite. Our results reveal that NirP1 is widely conserved in cyanobacteria and plays a crucial role in the coordination of C/N primary metabolism by targeting nitrite reductase.

Foster Care Involvement Among Youth With Intellectual and Developmental Disabilities.

Importance: Youth with intellectual and developmental disabilities (I/DD) are more likely to be placed in foster care than other youth. Examining the clinical and sociodemographic characteristics of youth with I/DD in the foster care system is critical for identifying disparities and understanding service needs. Objective: To produce a population-level analysis of youth with I/DD in foster care that examines differences in rates of foster care involvement based on race, ethnicity, age, and sex. Design, Setting, and Participants: This cross-sectional study involved all individuals with I/DD 21 years and younger enrolled in Medicaid through foster care in 2016 via data from Transformed Medicaid Statistical Information System (T-MSIS) Analytic Files (TAF) for all 50 US states and Washington, DC. As a key insurer of I/DD services and foster care, Medicaid claims offer a timely population-level analysis. Youth with I/DD were grouped into diagnostic subgroups: autism spectrum disorder (ASD) only, intellectual disability only, or ASD and ID. The data analysis took place from July 2022 to September 2023. Exposure: TAF data contain Medicaid enrollment information by month with a binary indicator of foster care involvement, and eligibility files identify race, ethnicity, age, and sex. Main Outcomes and Measures: The period prevalence of foster care involvement was determined among I/DD youth by diagnostic subgroups using an intersectional approach across race, ethnicity, age, and sex. Logistic regression examined associations between risk for foster care involvement and race, ethnicity, age, and sex. Results: A total of 39 143 youth with I/DD had foster care involvement in 2016. Black youth (adjusted odds ratio [aOR], 1.37; 95% CI, 1.28-1.47) and females (aOR, 1.18; 95% CI, 1.1-1.27) had increased likelihood for foster care involvement. The likelihood for foster care involvement increased with age in all groups relative to the age group 0 to 5 years old. Conclusions and Relevance: This study found that among youth with I/DD, Black youth and females faced higher risk for foster care involvement, and the likelihood of foster care involvement increased with age. There is an urgent need for research that focuses on addressing system-level factors that drive increased risk. Understanding the specific health needs of Black and female youth with I/DD is critical to ensure the formation, implementation, and monitoring of equitable delivery of health services.

Impact of body mass index on pathological response after neoadjuvant chemotherapy: results from the I-SPY 2 trial.

PURPOSE: Increased body mass index (BMI) has been associated with poor outcomes in women with breast cancer. We evaluated the association between BMI and pathological complete response (pCR) in the I-SPY 2 trial. METHODS: 978 patients enrolled in the I-SPY 2 trial 3/2010-11/2016 and had a recorded baseline BMI prior to treatment were included in the analysis. Tumor subtypes were defined by hormone receptor and HER2 status. Pretreatment BMI was categorized as obese (BMI ≥ 30 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and normal/underweight (< 25 kg/m2). pCR was defined as elimination of detectable invasive cancer in the breast and lymph nodes (ypT0/Tis and ypN0) at the time of surgery. Logistic regression analysis was used to determine associations between BMI and pCR. Event-free survival (EFS) and overall survival (OS) between different BMI categories were examined using Cox proportional hazards regression. RESULTS: The median age in the study population was 49 years. pCR rates were 32.8% in normal/underweight, 31.4% in overweight, and 32.5% in obese patients. In univariable analysis, there was no significant difference in pCR with BMI. In multivariable analysis adjusted for race/ethnicity, age, menopausal status, breast cancer subtype, and clinical stage, there was no significant difference in pCR after neoadjuvant chemotherapy for obese compared with normal/underweight patients (OR = 1.1, 95% CI 0.68-1.63, P = 0.83), and for overweight compared with normal/underweight (OR = 1, 95% CI 0.64-1.47, P = 0.88). We tested for potential interaction between BMI and breast cancer subtype; however, the interaction was not significant in the multivariable model (P = 0.09). Multivariate Cox regression showed there was no difference in EFS (P = 0.81) or OS (P = 0.52) between obese, overweight, and normal/underweight breast cancer patients with a median follow-up time of 3.8 years. CONCLUSION: We found no difference in pCR rates by BMI with actual body weight-based neoadjuvant chemotherapy in this biologically high-risk breast cancer population in the I-SPY2 trial.

The role of species ecology in predicting Toxoplasma gondii prevalence in wild and domesticated mammals globally.

Macroecological approaches can provide valuable insight into the epidemiology of globally distributed, multi-host pathogens. Toxoplasma gondii is a protozoan that infects any warm-blooded animal, including humans, in almost every habitat worldwide. Toxoplasma gondii infects its hosts through oocysts in the environment, carnivory of tissue cysts within intermediate host prey and vertical transmission. These routes of infection enable specific predictions regarding the ecological and life history traits that should predispose specific taxa to higher exposure and, thus infection rates of T. gondii. Using T. gondii prevalence data compiled from 485 studies representing 533 free-ranging wild mammalian species, we examined how ecological (habitat type, trophic level) and life history (longevity, vagility, gestation duration and torpor) traits influence T. gondii infection globally. We also compared T. gondii prevalence between wild and domesticated species from the same taxonomic families using data compiled from 540 studies of domestic cattle, sheep, and pigs. Across free-ranging wildlife, we found the average T. gondii prevalence was 22%, which is comparable to the global human estimate. Among ecological guilds, terrestrial species had lower T. gondii prevalence than aquatic species, with freshwater aquatic taxa having an increased prevalence compared to marine aquatic species. Dietary niches were also influential, with carnivores having an increased risk compared to other trophic feeding groups that have reduced tissue cyst exposure in their diet. With respect to influential life history traits, we found that more vagile wildlife species had higher T. gondii infection rates, perhaps because of the higher cumulative risk of infection during movement through areas with varying T. gondii environmental loads. Domestic farmed species had a higher T. gondii prevalence compared to free-ranging confamilial wildlife species. Through a macroecological approach, we determined the relative significance of transmission routes of a generalist pathogen, demonstrating an increased infection risk for aquatic and carnivorous species and highlighting the importance of preventing pathogen pollution into aquatic environments. Toxoplasma gondii is increasingly understood to be primarily an anthropogenically-associated pathogen whose dissemination is enhanced by ecosystem degradation and human subsidisation of free-roaming domestic cats. Adopting an ecosystem restoration approach to reduce one of the world's most common parasites would synergistically contribute to other initiatives in conservation, feline and wildlife welfare, climate change, food security and public health.

Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial-Efficacy and Biomarker Discovery.

PURPOSE: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial. PATIENTS AND METHODS: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy "graduates" if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. Patients received weekly paclitaxel (plus trastuzumab if HER2-positive) without (control) or with weekly intravenous trebananib, followed by doxorubicin/cyclophosphamide and surgery. Pathway-specific biomarkers were assessed for response prediction. RESULTS: There were 134 participants randomized to trebananib and 133 to control. Although trebananib did not graduate in any signature [phase III probabilities: Hazard ratio (HR)-negative (78%), HR-negative/HER2-positive (74%), HR-negative/HER2-negative (77%), and MP2 (79%)], it demonstrated high probability of superior pCR rates over control (92%-99%) among these subtypes. Trebananib improved 3-year event-free survival (HR 0.67), with no significant increase in adverse events. Activation levels of the Tie2 receptor and downstream signaling partners predicted trebananib response in HER2-positive disease; high expression of a CD8 T-cell gene signature predicted response in HR-negative/HER2-negative disease. CONCLUSIONS: The angiopoietin (Ang)/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority >90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.

Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer.

Importance: There has been little consideration of genomic risk of recurrence by breast cancer subtype despite evidence of racial disparities in breast cancer outcomes. Objective: To evaluate associations between clinical trial end points, namely pathologic complete response (pCR) and distant recurrence-free survival (DRFS), and race and examine whether gene expression signatures are associated with outcomes by race. Design, Setting, and Participants: This retrospective cohort study used data from the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2 (I-SPY 2) multicenter clinical trial of neoadjuvant chemotherapy with novel agents and combinations for patients with previously untreated stage II/III breast cancer. Analyses were conducted of associations between race and short- and long-term outcomes, overall and by receptor subtypes, and their association with 28 expression biomarkers. The trial enrolled 990 female patients between March 30, 2010, and November 5, 2016, with a primary tumor size of 2.5 cm or greater and clinical or molecular high risk based on MammaPrint or hormone receptor (HR)-negative/ERBB2 (formerly HER2 or HER2/neu)-positive subtyping across 9 arms. This data analysis was performed between June 10, 2021, and October 20, 2022. Exposure: Race, tumor receptor subtypes, and genomic biomarker expression of early breast cancer. Main Outcomes and Measures: The primary outcomes were pCR and DRFS assessed by race, overall, and by tumor subtype using logistic regression and Cox proportional hazards regression models. The interaction between 28 expression biomarkers and race, considering pCR and DRFS overall and within subtypes, was also evaluated. Results: The analytic sample included 974 participants (excluding 16 self-reporting as American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, or multiple races due to small sample sizes), including 68 Asian (7%), 120 Black (12%), and 786 White (81%) patients. Median (range) age at diagnosis was 47 (25-71) years for Asian, 49 (25-77) for Black, and 49 (23-73) years for White patients. The pCR rates were 32% (n = 22) for Asian, 30% for Black (n = 36), and 32% for White (n = 255) patients (P = .87). Black patients with HR-positive/ERBB2-negative tumors not achieving pCR had significantly worse DRFS than their White counterparts (hazard ratio, 2.28; 95% CI, 1.24-4.21; P = .01), with 5-year DRFS rates of 55% (n = 32) and 77% (n = 247), respectively. Black patients with HR-positive/ERBB2-negative tumors, compared with White patients, had higher expression of an interferon signature (mean [SD], 0.39 [0.87] and -0.10 [0.99]; P = .007) and, compared with Asian patients, had a higher mitotic score (mean [SD], 0.07 [1.08] and -0.69 [1.06]; P = .01) and lower estrogen receptor/progesterone receptor signature (mean [SD], 0.31 [0.90] and 1.08 [0.95]; P = .008). A transforming growth factor ß signature had a significant association with race relative to pCR and DRFS, with a higher signature associated with lower pCR and worse DRFS outcomes among Black patients only. Conclusions and Relevance: The findings show that women with early high-risk breast cancer who achieve pCR have similarly good outcomes regardless of race, but Black women with HR-positive/ERBB2-negative tumors without pCR may have worse DRFS than White women, highlighting the need to develop and test novel biomarker-informed therapies in diverse populations.

The Preserving Kidney Function in Children With CKD (PRESERVE) Study: Rationale, Design, and Methods.

Rationale & Objective: PRESERVE seeks to provide new knowledge to inform shared decision-making regarding blood pressure (BP) management for pediatric chronic kidney disease (CKD). PRESERVE will compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; expand the National Patient-Centered Clinical Research Network (PCORnet) common data model by adding pediatric- and kidney-specific variables and linking electronic health record data to other kidney disease databases; and assess the lived experiences of patients related to BP management. Study Design: Multicenter retrospective cohort study (clinical outcomes) and cross-sectional study (patient-reported outcomes [PROs]). Setting & Participants: PRESERVE will include approximately 20,000 children between January 2009-December 2022 with mild-moderate CKD from 15 health care institutions that participate in 6 PCORnet Clinical Research Networks (PEDSnet, STAR, GPC, PaTH, CAPRiCORN, and OneFlorida+). The inclusion criteria were ≥1 nephrologist visit and ≥2 estimated glomerular filtration rate (eGFR) values in the range of 30 to <90 mL/min/1.73 m2 separated by ≥90 days without an intervening value ≥90 mL/min/1.73 m2 and no prior dialysis or kidney transplant. Exposures: BP measurements (clinic-based and 24-hour ambulatory BP); urine protein; and antihypertensive treatment by therapeutic class. Outcomes: The primary outcome is a composite event of a 50% reduction in eGFR, eGFR of <15 mL/min/1.73 m2, long-term dialysis or kidney transplant. Secondary outcomes include change in eGFR, adverse events, and PROs. Analytical Approach: Longitudinal models for dichotomous (proportional hazards or accelerated failure time) and continuous (generalized linear mixed models) clinical outcomes; multivariable linear regression for PROs. We will evaluate heterogeneity of treatment effect by CKD etiology and degree of proteinuria and will examine variation in hypertension management and outcomes based on socio-demographics. Limitations: Causal inference limited by observational analyses. Conclusions: PRESERVE will leverage the PCORnet infrastructure to conduct large-scale observational studies that address BP management knowledge gaps for pediatric CKD, focusing on outcomes that are meaningful to patients. Plain-Language Summary: Hypertension is a major modifiable contributor to loss of kidney function in chronic kidney disease (CKD). The purpose of PRESERVE is to provide evidence to inform shared decision-making regarding blood pressure management for children with CKD. PRESERVE is a consortium of 16 health care institutions in PCORnet, the National Patient-Centered Clinical Research Network, and includes electronic health record data for >19,000 children with CKD. PRESERVE will (1) expand the PCORnet infrastructure for research in pediatric CKD by adding kidney-specific variables and linking electronic health record data to other kidney disease databases; (2) compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; and (3) assess the lived experiences of patients and caregivers related to blood pressure management.

Impact of Body Mass Index on Pathological Response after Neoadjuvant Chemotherapy: Results from the I-SPY 2 trial.

Purpose: Increased body mass index (BMI) has been associated with poor outcomes in women with breast cancer. We evaluated the association between BMI and pathological complete response (pCR) in the I-SPY 2 trial. Methods: 978 patientsenrolled in the I-SPY 2 trial 3/2010-11/2016 and had a recorded baseline BMI prior to treatment were included in the analysis. Tumor subtypes were defined by hormone receptor and HER2 status. Pretreatment BMI was categorized as obese (BMI≥30 kg/m2), overweight (25≤BMI < 30 kg/m2), and normal/underweight (< 25 kg/m2). pCR was defined as elimination of detectable invasive cancer in the breast and lymph nodes (ypT0/Tis and ypN0) at the time of surgery. Logistic regression analysis was used to determine associations between BMI and pCR. Event-free survival (EFS) and overall survival (OS) between different BMI categories were examined using Cox proportional hazards regression. Results: The median age in the study population was 49 years. pCR rates were 32.8% in normal/underweight, 31.4% in overweight, and 32.5% in obese patients. In univariable analysis, there was no significant difference in pCR with BMI. In multivariable analysis adjusted for race/ethnicity, age, menopausal status, breast cancer subtype, and clinical stage, there was no significant difference in pCR after neoadjuvant chemotherapy for obese compared with normal/underweight patients (OR = 1.1, 95% CI: 0.68-1.63, p = 0.83), and for overweight compared with normal/underweight (OR = 1, 95% CI: 0.64-1.47, p = 0.88). We tested for potential interaction between BMI and breast cancer subtype; however, the interaction was not significant in the multivariable model (p = 0.09). Multivariate Cox regression showed there was no difference in EFS (p = 0.81) or OS (p = 0.52) between obese, overweight, and normal/underweight breast cancer patients with a median follow-up time of 3.8 years. Conclusions: We found no difference in pCR rates by BMI with actual body weight based neoadjuvant chemotherapy in this biologically high-risk breast cancer population in the I-SPY2 trial.

Observational study of organisational responses of 17 US hospitals over the first year of the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic has required significant modifications of hospital care. The objective of this study was to examine the operational approaches taken by US hospitals over time in response to the COVID-19 pandemic. DESIGN, SETTING AND PARTICIPANTS: This was a prospective observational study of 17 geographically diverse US hospitals from February 2020 to February 2021. OUTCOMES AND ANALYSIS: We identified 42 potential pandemic-related strategies and obtained week-to-week data about their use. We calculated descriptive statistics for use of each strategy and plotted percent uptake and weeks used. We assessed the relationship between strategy use and hospital type, geographic region and phase of the pandemic using generalised estimating equations (GEEs), adjusting for weekly county case counts. RESULTS: We found heterogeneity in strategy uptake over time, some of which was associated with geographic region and phase of pandemic. We identified a body of strategies that were both commonly used and sustained over time, for example, limiting staff in COVID-19 rooms and increasing telehealth capacity, as well as those that were rarely used and/or not sustained, for example, increasing hospital bed capacity. CONCLUSIONS: Hospital strategies during the COVID-19 pandemic varied in resource intensity, uptake and duration of use. Such information may be valuable to health systems during the ongoing pandemic and future ones.

Psychosocial supports within pediatric nephrology practices: A pediatric nephrology research consortium survey.

BACKGROUND: The landscape of available psychosocial services within pediatric nephrology care is poorly characterized. However, the effects of kidney disease on emotional health and health-related quality of life are well documented, as is the impact of social determinants of health on kidney disease outcomes. The objectives of this study were to assess pediatric nephrologists' perceptions of available psychosocial services and to elucidate inequities in access to psychosocial care. METHODS: A web-based survey was distributed to members of the Pediatric Nephrology Research Consortium (PNRC). Quantitative analyses were performed. RESULTS: We received responses from 49 of the 90 PNRC centers. With regards to dedicated services, social work was most commonly available (45.5-100%), followed by pediatric psychology (0-57.1%) and neuropsychology (0-14.3%), with no centers having embedded psychiatry. Availability of psychosocial providers was positively associated with nephrology division size, such that as center size increased, access to various psychosocial providers increased. Notably, the majority of respondents indicated that perceived need for psychosocial support exceeds that which is currently available, even at centers with higher levels of current support. CONCLUSIONS: Within the US, there is wide variability in the availability of psychosocial services within pediatric nephrology centers despite a well-documented necessity for the provision of holistic care. Much work remains to better understand the variation in funding for psychosocial services and in utilization of psychosocial professionals in the pediatric nephrology clinic, and to inform key best practices for addressing the psychosocial needs of patients with kidney disease.

Assessing the Potential Efficacy of an Intervention for Incarcerated People With Mental Illness.

OBJECTIVE: This preliminary study tested the efficacy of an evidence-based correctional intervention (Thinking for a Change) with an adapted delivery to incarcerated people with mental illness. METHODS: A small-scale randomized controlled trial (N=47 men) was conducted. Outcomes were changes in aggression, number of behavioral infractions, and days in administrative segregation. Treatment targets were impulsivity, interpersonal problem-solving skills, and attitudes supportive of crime. Linear mixed-effects models were used to examine within-person and between-group differences over time, and nonparametric tests were used to examine between-group differences in criminal legal outcomes postintervention. RESULTS: Statistically significant within-person differences were found for all treatment targets and for one study outcome (aggression). Statistically significant differences in impulsivity were found between the experimental and control groups (B=-7.10, p=0.02). CONCLUSIONS: Existing evidence-based correctional interventions can affect the lives of people with mental illness. Accelerated research in this area may benefit people with mental illness at high risk for criminal legal system involvement.

Effectiveness of COVID-19 mRNA Vaccines in Preventing COVID-19-Associated Outpatient Visits and Hospitalizations Among American Indian and Alaska Native Persons, January-November 2021: A Test-Negative Case-Control Analysis Using Surveillance Data.

Background: Despite the disproportionate morbidity and mortality experienced by American Indian and Alaska Native (AI/AN) persons during the coronavirus disease 2019 (COVID-19) pandemic, few studies have reported vaccine effectiveness (VE) estimates among these communities. Methods: We conducted a test-negative case-control analysis among AI/AN persons aged ≥12 years presenting for care from January 1, 2021, through November 30, 2021, to evaluate the effectiveness of mRNA COVID-19 vaccines against COVID-19-associated outpatient visits and hospitalizations. Cases and controls were patients with ≥1 symptom consistent with COVID-19-like illness; cases were defined as those test-positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and controls were defined as those test-negative for SARS-CoV-2. We used unconditional multivariable logistic regression to estimate VE, defined as 1 minus the adjusted odds ratio for vaccination among cases vs controls. Results: The analysis included 207 cases and 267 test-negative controls. Forty-four percent of cases and 78% of controls received 2 doses of either BNT162b2 or mRNA-1273 vaccine. VE point estimates for 2 doses of mRNA vaccine were higher for hospitalized participants (94.6%; 95% CI, 88.0-97.6) than outpatient participants (86.5%; 95% CI, 63.0-95.0), but confidence intervals overlapped. Conclusions: Among AI/AN persons, mRNA COVID-19 vaccines were highly effective in preventing COVID-associated outpatient visits and hospitalizations. Maintaining high vaccine coverage, including booster doses, will reduce the burden of disease in this population.

Improving inclusion and well-being of trans and gender nonconforming collegiate student-athletes: foundational concepts from the National Collegiate Athletic Association Summit on Gender Identity and Student-Athlete Participation.

The National Collegiate Athletic Association (NCAA) Summit on Gender Identity and Student-Athlete Participation was convened to identify institutional/athletic department strategies that may support the well-being of trans and gender nonconforming (TGNC) collegiate student-athletes in the USA. The Summit's purview did not include policy-level changes to eligibility rules. A modified Delphi consensus process was used to identify strategies for supporting collegiate TGNC student-athlete well-being. Key steps included an exploration phase (learning, generating ideas), and an evaluation phase (rating ideas in terms of their utility and feasibility). Summit participants (n=60) included individuals meeting at least one of the following criteria: current or former TGNC athlete, academic or healthcare professional with topical expertise, collegiate athletics stakeholder who would be involved in implementing potential strategies, representative from leading sports medicine organisation, or representative from relevant NCAA membership committee. Summit participants identified strategies in the following domains: healthcare practices (patient-centred care and culturally sensitive care); education for all stakeholders involved in athletics; and administration (inclusive language, quality improvement processes). Summit participants also proposed ways that the NCAA, through its existing committee and governance structures, could help support the well-being of TGNC athletes. NCAA-focused concepts were in the following domains: policy making processes; eligibility and transfer processes; resource development and dissemination; and visibility and support for TGNC athletes. The strategies developed represent important and relevant approaches that member institutions, athletic departments, NCAA committees, governance bodies and other stakeholders might consider in their efforts to support TGNC student-athlete well-being.

Patient-Reported Outcomes Over 24 Months in Pediatric CKD: Findings From the MyKidneyHealth Cohort Study.

RATIONALE & OBJECTIVE: The lived experience of children with chronic kidney disease (CKD) is poorly characterized. We examined the associations between patient-reported outcome (PRO) scores measuring their fatigue, sleep health, psychological distress, family relationships, and global health with clinical outcomes over time in children, adolescents, and younger adults with CKD and investigated how the PRO scores of this group compare with those of other children, adolescents, and younger adults. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 212 children, adolescentss, and adults aged 8 to 21 years with CKD and their parents recruited from 16 nephrology programs across North America. PREDICTORS: CKD stage, disease etiology, and sociodemographic and clinical variables. OUTCOME: PRO scores over 2 years. ANALYTICAL APPROACH: We compared PRO scores in the CKD sample with a nationally representative general pediatric population (ages 8 to 17 years). Change of PROs over time and association of sociodemographic and clinical variables with PROs were assessed using multivariable regression models. RESULTS: For all time points, 84% of the parents and 77% of the children, adolescents, and younger adults completed PRO surveys . The baseline PRO scores for the participants with CKD revealed a higher burden of fatigue, sleep-related impairment, psychological distress, impaired global health, and poorer family relationships compared with the general pediatric population, with median score differences≥1 SD for fatigue and global health. The baseline PRO scores did not differ by CKD stage or glomerular versus nonglomerular etiology. Over 2 years, PROs were stable with a<1-point annual change on average on each measure and intraclass correlation coefficients ranging from 0.53 to 0.79, indicating high stability. Hospitalization and parent-reported sleep problems were associated with worse fatigue, psychological health, and global health scores (all P<0.04). LIMITATIONS: We were unable to assess responsiveness to change with dialysis or transplant. CONCLUSIONS: Children with CKD experience a high yet stable burden of impairment across numerous PRO measures, especially fatigue and global health, independent of disease severity. These findings underscore the importance of assessing PROs, including fatigue and sleep measures, in this vulnerable population. PLAIN-LANGUAGE SUMMARY: Children with chronic kidney disease (CKD) have many treatment demands and experience many systemic effects. How CKD impacts the daily life of a child is poorly understood. We surveyed 212 children, adolescents, and younger adults with CKD and their parents over 24 months to assess the participants' well-being over time. Among children, adolescents, and younger adults with CKD we found a very high and persistent burden of psychological distress that did not differ by degree of CKD or type of kidney disease. The participants with CKD endorsed greater impairment in fatigue and global health compared with healthy children, adolescents, and younger adults, and parent-reported sleep problems were associated with poorer patient-reported outcome (PRO) scores across all domains. These findings emphasize the importance of including PRO measures, including fatigue and sleep measures, into routine clinical care to optimize the lived experience of children with CKD.

Feasibility of recruiting in prisons during a randomized controlled trial with people with serious mental illness.

BACKGROUND: Successful participant recruitment is vital to the feasibly of intervention research. In the behavioral and social sciences, intervention researchers face a myriad of recruitment barriers, many of which stem from working in real-world settings and among hard-to-access populations. Optimizing recruitment efforts requires being intentional about study planning and resource allocation, carefully documenting the outcomes of recruitment efforts, and developing and implementing procedures and strategies to overcome anticipated recruitment barriers. METHODS: The current article presents recruitment flowcharts to illustrate (a) the multistep recruitment process and (b) the points of potential participant attrition during recruitment from a two-phase group-based intervention study conducted among individuals with serious mental illness incarcerated in a state prison system in the U.S. In addition, qualitative methods are used to examine strategies employed during the study to support recruitment efforts. RESULTS: Despite challenges, this study was able to achieve recruitment goals. Analyses found the majority of potential participant attrition occurred prior to informed consent, highlighting the need for studies to track recruitment efforts in more detail than is currently recommended by commonly used guidelines. Strategies to optimize recruitment efforts included maximizing recruiter availability, developing a responsive communication approach, demonstrating respect for facility procedures and operations, and ensuring peak preparedness. CONCLUSION: Careful documentation of recruitment efforts and the early deployment of recruitment strategies is vital to the feasibility of intervention studies conducted in real-world settings with hard-to-access populations. The publication of recruitment procedures and outcomes can help future researchers anticipate recruitment challenges and inform recruitment goals, timelines, and strategies.

Posttraumatic stress disorder and posttraumatic stress symptoms among adults with hemophilia A and B.

Background: Persons with hemophilia may encounter various traumatic experiences related to their bleeding disorder throughout their lifetime. Little is known about the clinical impact of disease-related trauma on this population. Objectives: To explore the prevalence of posttraumatic stress disorder (PTSD) and posttraumatic stress symptoms in adults with hemophilia A and B and characterize the traumatic experiences they report. Methods: An online survey tool collecting data on participant characteristics and a validated questionnaire containing the PTSD checklist for Diagnostic and Statistical Manual of Mental Disorders 5 were distributed via Research Electronic Data Capture to adults with hemophilia A and B during their annual visit to their hemophilia treatment center. Participants were asked about traumatic experiences specific to their hemophilia prior to self-administering the PTSD checklist for Diagnostic and Statistical Manual of Mental Disorders 5 questionnaire. Results: Survey responses from 178 individuals across 3 hemophilia treatment centers were included in the analysis, representing a 70% response rate. One hundred one (56.7%) participants identified a hemophilia-related traumatic event, and 21 (11.8%) participants met criteria for a provisional diagnosis of PTSD. Multivariable analysis showed higher odds of a positive PTSD screen in participants with noninfectious (odds ratio [OR], 13.89; 95% CI, 2.23-86.62) and infectious comorbidities (OR, 11.18; 95% CI, 1.34-93.45) and in participants with >1 mental health comorbidity (OR, 10.07; 95% CI, 2.39-42.52). On the contrary, age >46 years (OR, 0.6; 95% CI, 0.01-0.62) and higher education (OR, 0.25; 95% CI, 0.07-0.88) reduced odds of PTSD. Conclusion: Persons with hemophilia are at risk of developing PTSD and posttraumatic stress symptoms. These data support the need for trauma screening, psychosocial services in the bleeding disorders community, and provision of trauma-informed care by providers.

Safety and efficacy of HSP90 inhibitor ganetespib for neoadjuvant treatment of stage II/III breast cancer.

HSP90 inhibitors destabilize oncoproteins associated with cell cycle, angiogenesis, RAS-MAPK activity, histone modification, kinases and growth factors. We evaluated the HSP90-inhibitor ganetespib in combination with standard chemotherapy in patients with high-risk early-stage breast cancer. I-SPY2 is a multicenter, phase II adaptively randomized neoadjuvant (NAC) clinical trial enrolling patients with stage II-III breast cancer with tumors 2.5 cm or larger on the basis of hormone receptors (HR), HER2 and Mammaprint status. Multiple novel investigational agents plus standard chemotherapy are evaluated in parallel for the primary endpoint of pathologic complete response (pCR). Patients with HER2-negative breast cancer were eligible for randomization to ganetespib from October 2014 to October 2015. Of 233 women included in the final analysis, 140 were randomized to the standard NAC control; 93 were randomized to receive 150 mg/m2 ganetespib every 3 weeks with weekly paclitaxel over 12 weeks, followed by AC. Arms were balanced for hormone receptor status (51-52% HR-positive). Ganetespib did not graduate in any of the biomarker signatures studied before reaching maximum enrollment. Final estimated pCR rates were 26% vs. 18% HER2-negative, 38% vs. 22% HR-negative/HER2-negative, and 15% vs. 14% HR-positive/HER2-negative for ganetespib vs control, respectively. The predicted probability of success in phase 3 testing was 47% HER2-negative, 72% HR-negative/HER2-negative, and 19% HR-positive/HER2-negative. Ganetespib added to standard therapy is unlikely to yield substantially higher pCR rates in HER2-negative breast cancer compared to standard NAC, and neither HSP90 pathway nor replicative stress expression markers predicted response. HSP90 inhibitors remain of limited clinical interest in breast cancer, potentially in other clinical settings such as HER2-positive disease or in combination with anti-PD1 neoadjuvant chemotherapy in triple negative breast cancer.Trial registration: www.clinicaltrials.gov/ct2/show/NCT01042379.