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PURPOSE: Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric malignancy with myelodysplastic and myeloproliferative features. Curative treatment is restricted to hematopoietic stem-cell transplantation. Fludarabine combined with cytarabine (FLA) and 5-azacitidine (AZA) monotherapy are commonly used pre-transplant therapies. Here, we present a drug screening strategy using a flow cytometry-based precision medicine platform to identify potential additional therapeutic vulnerabilities. METHODS: We screened 120 dual- and 10 triple-drug combinations (DCs) on peripheral blood (n = 21) or bone marrow (n = 6) samples from 27 children with JMML to identify DCs more effectively reducing leukemic cells than the DCs components on their own. If fewer leukemic cells survived a DC ex vivo treatment compared with that DCs most effective component alone, the drug effect was referred to as cooperative. The difference between the two resistant fractions is the effect size. RESULTS: We identified 26 dual- and one triple-DC more effective than their components. The differentiation agent tretinoin (TRET; all-trans retinoic acid) reduced the resistant fraction of FLA in 19/21 (90%) samples (decrease from 15% [2%-61%] to 11% [2%-50%] with a mean effect size of 3.8% [0.5%-11%]), and of AZA in 19/25 (76%) samples (decrease from 69% [34%-100+%] to 47% [17%-83%] with a mean effect size of 16% [0.3%-40%]). Among the resistant fractions, the mean proportion of CD38+ cells increased from 7% (0.03%-25%; FLA) to 17% (0.3%-38%; FLA + TRET) or from 10% (0.2%-31%; AZA) to 51% (0.8%-88%; AZA + TRET). CONCLUSION: TRET enhanced the effects of FLA and AZA in ex vivo assays with primary JMML samples.

FIP1L1-RARA-a ssociated neoplasm is a very rare and aggressive disease, with only 3 previously reported cases in the literature. Here, we describe a 9-month-old boy who presented with a FIP1L1-RARA fusion-associated myelodysplastic/myeloproliferative neoplasm-like overlap syndrome, with similarities and distinct features to both acute promyelocytic leukemia and juvenile myelomonocytic leukemia. Using a combined approach of chemotherapy, differentiating agents, and allogeneic hematopoietic stem cell transplant (allo-HCT), this patient remains in remission 20 months after allo-HCT. To our knowledge, this is only the second published pediatric case involving this condition and the only case with a favorable long-term outcome. Given the aggressive disease described in the previously published case report, as well as the successful treatment course described, the combinatorial use of chemotherapy, differentiation therapy, and allo-HCT for treatment of FIP1L1-RARA fusion-associated myeloid neoplasms should be considered.

BackgroundThe In-Center Hemodialysis Consumer Assessment of Healthcare Providers and Systems (ICH CAHPS) Survey is the first patient reported outcome measure included in the U.S. Medicare End Stage Renal Disease Quality Incentive Program. Administered twice yearly, it assesses in-center dialysis experience and survey responses are tied to dialysis facility payments. Low response rates, currently approximately 35%, raise concern for possible underrepresentation of patient groups.MethodsCross-sectional analysis of survey administration in 2012 to all in-center hemodialysis patients in Dialysis Clinic, Inc. (DCI) facilities nationally over 18 years old who received hemodialysis at their facility for at least 3 months. Patient-level covariates included demographic, clinical, laboratory, and functional characteristics. Random effects multivariable logistic regression was used to assess survey non-response.ResultsAmong 11,055 eligible patients 6541 (59%) were non-responders. Of the remaining 4514 responders, 549 (14%) surveys were not usable due to presence of proxy help or incomplete responses. Non-responders were more likely to be men, non-white, younger, single, dual Medicare/Medicaid eligible, less educated, non-English speaking, and not active on the transplant list; non-responders had longer ESRD vintage, lower body mass index, lower serum albumin, worse functional status, and more hospitalizations, missed treatments, and shortened treatments. Similar associations were found using more parsimonious multivariable analyses and after imputing missing data.ConclusionsNon-responders to the ICH CAHPS significantly differed from responders, broadly spanning individuals with fewer socioeconomic advantages and greater illness burden, raising limitations in interpreting facility survey results. Future research should assess reasons for non-response to improve ICH CAHPS generalizability and utility.

This article focuses on strategies that can be used to help build a strong and inclusive networking foundation for orthopaedic residency and beyond. It stresses the importance of building friendship with medical classmates which can lead to academic collaborations, supplementary perspective on residency training and orthopaedics and a sense community beyond a person's residency. It also notes that social support among orthopaedic surgery residents is crucial to reducing the risk of burnout.

School-based non-pharmacological interventions are an important part of the treatment of attention-deficit/hyperactivity disorder (ADHD). We aimed to systematically review qualitative literature relating to the experience of and attitudes towards school-based non-pharmacological interventions for ADHD. Systematic searches of 20 electronic databases were undertaken. Reviewers screened titles, abstracts and full reports of studies, before extracting data and critically appraising 33 included papers. Studies were synthesised using meta-ethnographic methods. Four-key interrelated themes were identified: (1) individualising interventions, (2) structure of interventions, (3) barriers to effectiveness, (4) perceived moderators and impact of interventions. The perceived effectiveness of interventions used in school settings is reported to vary. Therefore, flexible, tailored interventions ought to hold potential. However, highly individualised interventions may negatively affect children with ADHD. Findings point to the need for school-based interventions to take into account the wider school context, as well as core symptoms of ADHD.

A review of 13 years of research into antecedents of university students' grade point average (GPA) scores generated the following: a comprehensive, conceptual map of known correlates of tertiary GPA; assessment of the magnitude of average, weighted correlations with GPA; and tests of multivariate models of GPA correlates within and across research domains. A systematic search of PsycINFO and Web of Knowledge databases between 1997 and 2010 identified 7,167 English-language articles yielding 241 data sets, which reported on 50 conceptually distinct correlates of GPA, including 3 demographic factors and 5 traditional measures of cognitive capacity or prior academic performance. In addition, 42 non-intellective constructs were identified from 5 conceptually overlapping but distinct research domains: (a) personality traits, (b) motivational factors, (c) self-regulatory learning strategies, (d) students' approaches to learning, and (e) psychosocial contextual influences. We retrieved 1,105 independent correlations and analyzed data using hypothesis-driven, random-effects meta-analyses. Significant average, weighted correlations were found for 41 of 50 measures. Univariate analyses revealed that demographic and psychosocial contextual factors generated, at best, small correlations with GPA. Medium-sized correlations were observed for high school GPA, SAT, ACT, and A level scores. Three non-intellective constructs also showed medium-sized correlations with GPA: academic self-efficacy, grade goal, and effort regulation. A large correlation was observed for performance self-efficacy, which was the strongest correlate (of 50 measures) followed by high school GPA, ACT, and grade goal. Implications for future research, student assessment, and intervention design are discussed. (Contains 11 tables and 1 figure.)