Assessing health behavior change and comparing remote, hybrid and in-person implementation of a school-based health promotion and coaching program for adolescents from low-income communities.

To assess the impact of a school-based health intervention on adolescents' health knowledge, psychosocial assets and health behaviors, including comparisons of implementation mode: remote, hybrid or in-person. The Stanford Youth Diabetes Coaches Program, an 8-week, school-based health promotion and coaching skills program, was offered to adolescents (ages 14-18 years) from four low-income US communities. Mode of program implementation was remote, hybrid or in-person. Participants completed online pre- and postsurveys. Analysis included paired t-tests, linear regression and qualitative coding. From Fall 2020 to Fall 2021, 262 adolescents enrolled and 179 finished the program and completed pre- and postsurveys. Of the 179, 80% were female, with a mean age of 15.9 years; 22% were Asian; 8% were Black or African American; 25% were White; and 40% were Hispanic. About 115 participants were remote, 25 were hybrid and 39 were in-person. Across all participants, significant improvements (P < 0.01) were reported in health knowledge, psychosocial assets (self-esteem, self-efficacy and problem-solving) and health behaviors (physical activity, nutrition and stress reduction). After adjusting for sex and age, these improvements were roughly equivalent across the three modes of delivery. Participation was associated with significant improvements in adolescent health behaviors. Furthermore, remote mode of instruction was just as effective as in-person and hybrid modes.

Visual and whole-body quantitative analyses of 68 Ga-DOTATATE PET/CT for prognosis of outcome after PRRT with 177Lu-DOTATATE.

BACKGROUND: Somatostatin receptors (SSTR) represent an ideal target for nuclear theranostics applications in neuroendocrine tumors (NET). Studies suggest that high uptake on SSTR-PET is associated with response to SSTR peptide receptor radionuclide therapy (PRRT). The purpose of this study was to evaluate the role of baseline whole-body (WB) 68 Ga-DOTATATE PET/CT (SSTR-PET) quantitative parameters, and the presence of NET lesions without uptake on SSTR-PET, as outcome prognosticator in patients with NET treated with PRRT. METHODS: Patients with NET who underwent at least 4 177Lu-DOTATATE PRRT cycles between 07/2016 and 03/2021 were included in this retrospective analysis if they fulfilled the following inclusion criteria: SSTR-PET within 6 months of 1st PRRT cycle, follow-up CT and/or MRI performed > 6 months after the 4th cycle of PRRT. The SSTR-PET analysis consisted of a visual and a quantitative analysis done independently by two board-certified physicians. The visual analysis assessed the presence of NET lesions visible on the SSTR-PET co-registered CT. The quantitative analysis consisted in contouring all SSTR-avid lesions on SSTR-PET and extracting WB quantitative parameters: SUVmean (WB-SUVmean), SUVmax of the lesion with highest uptake (H-SUVmax), and tumor volume (WB-TV). WB-SSTR-PET parameters and the presence of SSTR-PET-negative lesions were correlated to radiologic response (assessed by RECIST 1.1 criteria) and progression-free survival (PFS). Fisher's exact test, Mann-Whitney's U test and Kaplan-Meier curves with Cox-regression analysis were used for the statistical analysis. RESULTS: Forty patients (F/M: 21/19; 34/40 with gastro-entero-pancreatic (GEP) NET, 6/40 with non-GEP NET) were included in the analysis. The median follow-up period after the 4th PRRT cycle was 25.7 months (range 15.2-59.1). Fourteen/40 (35%) patients showed radiologic response (RECIST PR). PFS event was observed in 17/40 (42.5%) patients. Thirteen/40 (32.5%) patients had SSTR-PET-negative lesions at baseline. Higher WB-SUVmean and H-SUVmax were associated with better response (p = 0.015 and 0.005, respectively). The presence of SSTR-PET-negative lesions and lower WB-SUVmean were associated with shorter PFS (p = 0.026 and 0.008, respectively). CONCLUSION: Visual and quantitative analyses of baseline SSTR-PET can yield valuable information to prognosticate outcomes after 177Lu-DOTATATE PRRT.

Cancer treatment refusal decisions in advanced cancer: a retrospective case-control study.

OBJECTIVE: Cancer remains one of the leading causes of death worldwide. Despite advancements in anticancer therapy, some patients decide against treatment. Our study focused on characterising therapy refusal in advanced-stage malignancies and further determining if certain variables significantly correlated with refusal, compared with acceptance. METHODS: Our inclusion criteria were patients aged 18-75 years, stage IV cancers between 1 January 2010 and 31 December 2015 and treatment refusal (cohort 1 (C1)). A randomly selected group of patients with stage IV cancers who accepted treatment within the same timeframe was used for comparison (cohort 2 (C2)). RESULTS: There were 508 patients in C1 and 100 patients in C2. Female sex was associated with treatment acceptance (51/100, 51.0%) than refusal (201/508, 39.6%); p=0.03. There were no associations between treatment decisions and race, marital status, BMI, tobacco use, previous cancer history, or family cancer history. Government-funded insurance was associated with treatment refusal (337/508, 66.3%) than acceptance (35/100, 35.0%); p<0.001. Age was associated with refusal (p<0.001). Average age of C1 was 63.1 years (SD:8.1) and C2 was 59.2 years (SD:9.9). Only 19.1% (97/508) in C1 were referred to palliative medicine, with 18% (18/100) in C2; p=0.8. There was a trend for patients who accepted therapy to have more comorbidities per the Charlson Comorbidity Index(p=0.08). The treatment of psychiatric disorders after cancer diagnosis was inversely associated with treatment refusal (p<0.001). CONCLUSIONS: The treatment of psychiatric disorders after cancer diagnosis was associated with cancer treatment acceptance. Male sex, older age and government-funded health insurance were associated with treatment refusal in patients with advanced cancer. Those who refused treatment were not increasingly referred to palliative medicine.

The association between isometric strength and cognitive function in adults with cerebral palsy.

Background: The literature supports quantifying the maximum force/tension generated by one's forearm muscles such as the hand grip strength (HGS) to screen for physical and cognitive frailty in older adults. Thus, we postulate that individuals with cerebral palsy (CP), who are at higher risk for premature aging, could benefit from tools that objectively measure muscle strength as a functional biomarker to detect frailty and cognitive decline. This study assesses the clinical relevancy of the former and quantifies isometric muscle strength to determine its association with cognitive function in adults with CP. Methods: Ambulatory adults with CP were identified from a patient registry and were enrolled into this study. Peak rate of force development (RFD) and maximum voluntary isometric contraction of the quadriceps were measured using a commercial isokinetic machine, while HGS was collected with a clinical dynamometer. Dominant and non-dominant side were identified. Standardized cognitive assessments, including the Wechsler Memory and Adult Intelligence Scales IV, Short Test of Mental Status, and the Patient-Reported Outcomes Measurement Information System (PROMIS®) were used to evaluate cognitive function. Results: A total of 57 participants (32 females; mean age 24.3 [SD 5.3]; GMFCS levels I-IV) were included in the analysis. Although dominant and non-dominant RFD and HGS measures were associated with cognitive function, non-dominant peak RFD showed the strongest associations with cognitive function. Conclusion: RFD capacity may reflect age-related neural and physical health and could be a better health indicator than HGS in the CP population.

Feasibility and Assessment of a Cascade Traceback Screening Program (FACTS): Protocol for a Multisite Study to Implement and Assess an Ovarian Cancer Traceback Cascade Testing Program.

Ovarian cancer (OVCA) patients may carry genes conferring cancer risk to biological family; however, fewer than one-quarter of patients receive genetic testing. "Traceback" cascade testing -outreach to potential probands and relatives-is a possible solution. This paper outlines a funded study (U01 CA240747-01A1) seeking to determine a Traceback program's feasibility, acceptability, effectiveness, and costs. This is a multisite prospective observational feasibility study across three integrated health systems. Informed by the Conceptual Model for Implementation Research, we will outline, implement, and evaluate the outcomes of an OVCA Traceback program. We will use standard legal research methodology to review genetic privacy statutes; engage key stakeholders in qualitative interviews to design communication strategies; employ descriptive statistics and regression analyses to evaluate the site differences in genetic testing and the OVCA Traceback testing; and assess program outcomes at the proband, family member, provider, system, and population levels. This study aims to determine a Traceback program's feasibility and acceptability in a real-world context. It will account for the myriad factors affecting implementation, including legal issues, organizational- and individual-level barriers and facilitators, communication issues, and program costs. Project results will inform how health care providers and systems can develop effective, practical, and sustainable Traceback programs.

Using pharmacists to improve risk stratification and management of stage 3A chronic kidney disease: a feasibility study.

BACKGROUND: Measurement of albuminuria to stratify risk in chronic kidney disease (CKD) is not done universally in the primary care setting despite recommendation in KDIGO (Kidney Disease Improving Global Outcomes) guidelines. Pharmacist medication therapy management (MTM) may be helpful in improving CKD risk stratification and management. METHODS: We conducted a pragmatic, cluster-randomized trial using seven primary care clinic sites in the Geisinger Health System to evaluate the feasibility of pharmacist MTM in patients with estimated glomerular filtration rate (eGFR) 45-59 ml/min/1.73 m2 and uncontrolled blood pressure (≥150/85 mmHg). In the three pharmacist MTM sites, pharmacists were instructed to follow a protocol aimed to improve adherence to KDIGO guidelines on testing for proteinuria and lipids, and statin and blood pressure medical therapy. In the four control clinics, patients received usual care. The primary outcome was proteinuria screening over a follow-up of 1 year. A telephone survey was administered to physicians, pharmacists, and patients in the pharmacist MTM arm at the end of the trial. RESULTS: Baseline characteristics were similar between pharmacist MTM (n = 24) and control (n = 23) patients, although pharmacist MTM patients tended to be younger (64 vs. 71 y; p = 0.06) and less likely to have diabetes (17 % vs. 35 %; p = 0.2) or baseline proteinuria screening (41.7 % vs. 60.9 %, p = 0.2). Mean eGFR was 54 ml/min/1.73 m2 in both groups. The pharmacist MTM intervention did not significantly improve total proteinuria screening at the population level (OR 2.6, 95 % CI: 0.5-14.0; p = 0.3). However, it tended to increase screening of previously unscreened patients (78.6 % in the pharmacist MTM group compared to 33.3 % in the control group; OR 7.3, 95 % CI: 0.96-56.3; p = 0.05). In general, the intervention was well-received by patients, pharmacists, and providers, who agreed that pharmacists could play an important role in CKD management. A few patients contacted the research team to express anxiety about having a CKD diagnosis without prior knowledge. CONCLUSIONS: Pharmacist MTM may be useful in improving risk stratification and management of CKD in the primary care setting, although implementation requires ongoing education and multidisciplinary collaboration and careful communication regarding CKD diagnosis. Future studies are needed to establish the effectiveness of pharmacist MTM on slowing CKD progression and improvement in cardiovascular outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02208674 Registered August 1, 2014, first patient enrolled September 30, 2014.

No association of labor epidural analgesia with cerebral palsy in children.

BACKGROUND: Some pregnant women avoid labor epidural analgesia because of their concerns about risk of cerebral palsy in children. Although it is believed that labor epidural does not contribute to cerebral palsy, to our knowledge no study has been published to specifically address this concern. We carried out a retrospective case-control study to investigate whether labor epidural analgesia is associated with cerebral palsy in children. METHODS: This study used data that were collected and entered into the Geisinger electronic health records between January 2004 and January 2013. During this period, 20,929 children were born at Geisinger hospitals. Among them, 50 children were diagnosed with cerebral palsy, and 20 of those were born vaginally. Each of these 20 cerebral palsy children was matched with up to 5 non-cerebral palsy children born at the same hospitals in the same timeframe using propensity scoring methods. Analgesia was classified as epidural (including epidural or combined spinal and epidural) or non-epidural. Conditional logistic regression was used to compare the percentages of deliveries with each analgesia type between the cerebral palsy and non-cerebral palsy groups. RESULTS: In the non-cerebral palsy group, the percentage of patients receiving labor epidural analgesia was 72 %, and in the cerebral palsy group the percentage was 45 %. There was no significant difference between non-cerebral palsy and cerebral palsy groups (odds ratio, 0.57; 95 % confidence interval, 0.14-2.24; p = 0.42). CONCLUSION: We found no association between the use of labor epidural analgesia and the occurrence of cerebral palsy in children.

Bariatric surgery is associated with improvement in kidney outcomes.

Severe obesity is associated with increased risk of kidney disease. Whether bariatric surgery reduces the risk of adverse kidney outcomes is uncertain. To resolve this we compared the risk of estimated glomerular filtration rate (eGFR) decline of ≥30% and doubling of serum creatinine or end-stage renal disease (ESRD) in 985 patients who underwent bariatric surgery with 985 patients who did not undergo such surgery. Patients were matched on demographics, baseline body mass index, eGFR, comorbidities, and previous nutrition clinic use. Mean age was 45 years, 97% were white, 80% were female, and 33% had baseline eGFR <90 ml/min per 1.73 m(2). Mean 1-year weight loss was 40.4 kg in the surgery group compared with 1.4 kg in the matched cohort. Over a median follow-up of 4.4 years, 85 surgery patients had an eGFR decline of ≥30% (22 had doubling of serum creatinine/ESRD). Over a median follow-up of 3.8 years, 177 patients in the matched cohort had an eGFR decline of ≥30% (50 had doubling of serum creatinine/ESRD). In adjusted analysis, bariatric surgery patients had a significant 58% lower risk for an eGFR decline of ≥30% (hazard ratio 0.42, 95% confidence interval 0.32-0.55) and 57% lower risk of doubling of serum creatinine or ESRD (hazard ratio 0.43, 95% confidence interval: 0.26-0.71) compared with the matched cohort. Results were generally consistent among subgroups of patients with and without eGFR <90 ml/min per 1.73 m(2), hypertension, and diabetes. Thus, bariatric surgery may be an option to prevent kidney function decline in severely obese individuals.

Prevalence of Functional Gastrointestinal Disorders in Children and Adolescents.

OBJECTIVES: To determine the prevalence of functional gastrointestinal (GI) disorders (FGIDs) in children and adolescents in a representative community sample of the US. STUDY DESIGN: The study recruited a general population sample of mothers (n = 949) of children and adolescents aged 4-18 years. Child and adolescent GI symptoms were assessed using parental report through online questionnaires, including the Questionnaire on Pediatric Gastrointestinal Symptoms and the PedsQL4.0 Generic Core Scale. Parental GI symptoms, and demographic characteristics were also assessed. The data was used to determine prevalence of FGIDs. RESULTS: Using Rome III criteria by parental report, 23.1% of children and adolescents qualified for at least 1 FGID. Functional constipation and abdominal migraine were the most common FGIDs. All 10 child/adolescent FGIDs occurred, except rumination. Significant prevalence differences were not found between sexes, except in functional constipation, which was more prevalent in males than females (P = .022). There were no significant prevalence differences between racial or ethnic groups. Children who met criteria for an FGID had lower quality of life (median = 76.4) than children who did not (median = 89.6; P < .001). Children were more likely to qualify for a FGID if their parent also qualified for a FGID (P < .01). CONCLUSIONS: FGIDs are common in children and adolescents in the US. There are no significant differences in FGIDs between sex, race, or ethnic groups, except in functional constipation. There is overlap between parental and child FGID symptoms. Children with a FGID report a lower quality of life than healthy children.

Application of chemoproteomics to drug discovery: identification of a clinical candidate targeting hsp90.

A chemoproteomics-based drug discovery strategy is presented that utilizes a highly parallel screening platform, encompassing more than 1000 targets, with a focused chemical library prior to target selection. This chemoproteomics-based process enables a data-driven selection of both the biological target and chemical hit after the screen is complete. The methodology has been exemplified for the purine binding proteome (proteins utilizing ATP, NAD, FAD). Screening of an 8000 member library yielded over 1500 unique protein-ligand interactions, which included novel hits for the oncology target Hsp90. The approach, which also provides broad target selectivity information, was used to drive the identification of a potent and orally active Hsp90 inhibitor, SNX-5422, which is currently in phase 1 clinical studies.

Discovery of novel 2-aminobenzamide inhibitors of heat shock protein 90 as potent, selective and orally active antitumor agents.

A novel class of heat shock protein 90 (Hsp90) inhibitors was developed from an unbiased screen to identify protein targets for a diverse compound library. These indol-4-one and indazol-4-one derived 2-aminobenzamides showed strong binding affinity to Hsp90, and optimized analogues exhibited nanomolar antiproliferative activity across multiple cancer cell lines. Heat shock protein 70 (Hsp70) induction and specific client protein degradation in cells on treatment with the inhibitors supported Hsp90 inhibition as the mechanism of action. Computational chemistry and X-ray crystallographic analysis of selected member compounds clearly defined the protein-inhibitor interaction and assisted the design of analogues. 4-[6,6-Dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]-2-[(trans-4-hydroxycyclohexyl)amino]benzamide (SNX-2112, 9) was identified as highly selective and potent (IC(50) Her2 = 11 nM, HT-29 = 3 nM); its prodrug amino-acetic acid 4-[2-carbamoyl-5-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-phenylamino]-cyclohexyl ester methanesulfonate (SNX-5422, 10) was orally bioavailable and efficacious in a broad range of xenograft tumor models (e.g. 67% growth delay in a HT-29 model) and is now in multiple phase I clinical trials.

Prevalence of antihypertensive, antidiabetic, and dyslipidemic prescription medication use among children and adolescents.

OBJECTIVE: To document trends in the use of prescription medications indicated for types 1 and 2 diabetes mellitus, hypertension, and dyslipidemia among children and adolescents. DESIGN: Serial, cross-sectional study. SETTING: Age-eligible children and adolescents with prescription drug benefits managed by CVS Caremark, a pharmacy benefits manager. PARTICIPANTS: Commercially insured US children and adolescents aged 6 to 18 years. Population size varied by month from approximately 5.3 million to 6 million individuals. MAIN OUTCOME MEASURE: Monthly prevalence of prescription drug use, measured from September 1, 2004, through June 30, 2007. RESULTS: The 1-month prevalence of antihypertensive, dyslipidemic, or oral antidiabetic medication or insulin use increased 15.2% from 3.3 per 1000 youths in November 2004 to 3.8 per 1000 youths in June 2007. The 16- to 18-year-olds had the highest prevalence overall, but the greatest rate of increase was found among 6- to 11-year-olds: 18.7% for girls and 17.3% for boys. Among antihypertensive medications, beta-blockers had the highest prevalence (1.5 per 1000 youths), followed by angiotensin-converting enzyme inhibitors, diuretics, calcium channel blockers, and angiotensin II receptor blockers. For 6- to 11-year-olds, angiotensin-converting enzyme inhibitor use increased 27.7% among girls and 25.2% among boys. Dyslipidemia therapy, which was dominated by statin use, declined 22.9%. CONCLUSIONS: The increasing use of oral antidiabetic and antihypertensive pharmacotherapy among children and adolescents, especially in the younger age group, indicates either an increased awareness of treatment needs or increased incidence of cardiovascular risk factors typically associated with adult populations. The decrease in treatment of dyslipidemia may reflect the ongoing controversy regarding statin use.