Data fusion for predicting long-term program impacts.

Policymakers often require information on programs' long-term impacts that is not available when decisions are made. For example, while rigorous evidence from the Oregon Health Insurance Experiment (OHIE) shows that having health insurance influences short-term health and financial measures, the impact on long-term outcomes, such as mortality, will not be known for many years following the program's implementation. We demonstrate how data fusion methods may be used address the problem of missing final outcomes and predict long-run impacts of interventions before the requisite data are available. We implement this method by concatenating data on an intervention (such as the OHIE) with auxiliary long-term data and then imputing missing long-term outcomes using short-term surrogate outcomes while approximating uncertainty with replication methods. We use simulations to examine the performance of the methodology and apply the method in a case study. Specifically, we fuse data on the OHIE with data from the National Longitudinal Mortality Study and estimate that being eligible to apply for subsidized health insurance will lead to a statistically significant improvement in long-term mortality.

Estimating generalized propensity scores with survey and attrition weighted data.

Prior work in causal inference has shown that using survey sampling weights in the propensity score estimation stage and the outcome model stage for binary treatments can result in a more robust estimator of the effect of the binary treatment being analyzed. However, to date, extending this work to continuous treatments and exposures has not been explored nor has consideration been given for how to handle attrition weights in the propensity score model. Nonetheless, generalized propensity score (GPS) analyses are being used for estimating continuous treatment effects on outcomes when researchers have observational data, and those data sets often have survey or attrition weights that need to be accounted for in the analysis. Here, we extend prior work and show with analytic results that using survey sampling or attrition weights in the GPS estimation stage and the outcome model stage for continuous treatments can result in a more robust estimator than one that does not. Simulation study results show that, although using weights in both estimation stages is sufficient for robust estimation, it is not necessary and unbiased estimation is possible in some cases under various approaches to using weights in estimation. Analysts do not know if the conditions of our simulation studies hold, so use of weights in both estimation stages might provide insurance for reducing potential bias. We discuss the implications of our results in the context of an empirical example.

The efficacy of combination treatment with elotuzumab and lenalidomide is dependent on crosstalk between natural killer cells, monocytes and myeloma cells.

Patients with refractory relapsed multiple myeloma respond to combination treatment with elotuzumab and lenalidomide. The mechanisms underlying this observation are not fully understood. Furthermore, biomarkers predictive of response have not been identified to date. To address these issues, we used a humanized myeloma mouse model and adoptive transfer of human natural killer (NK) cells to show that elotuzumab and lenalidomide treatment controlled myeloma growth, and this was mediated through CD16 on NK cells. In co-culture studies, we showed that peripheral blood mononuclear cells from a subset of patients with refractory relapsed multiple myeloma were effective killers of OPM2 myeloma cells when treated with elotuzumab and lenalidomide, and this was associated with significantly increased expression of CD54 on OPM2 cells. Furthermore, elotuzumab- and lenalidomide-induced OPM2 cell killing and increased OPM2 CD54 expression were dependent on both monocytes and NK cells, and these effects were not mediated by soluble factors alone. At the transcript level, elotuzumab and lenalidomide treatment significantly increased OPM2 myeloma cell expression of genes for trafficking and adhesion molecules, NK cell activation ligands and antigen presentation molecules. In conclusion, our findings suggest that multiple myeloma patients require elotuzumab- and lenalidomide-mediated upregulation of CD54 on autologous myeloma cells, in combination with NK cells and monocytes to mediate an effective anti-tumor response. Furthermore, our data suggest that increased myeloma cell CD54 expression levels could be a powerful predictive biomarker for response to elotuzumab and lenalidomide treatment.

The quality of occupational healthcare for carpal tunnel syndrome, healthcare expenditures, and disability outcomes: A prospective observational study.

INTRODUCTION/AIMS: In prior work, higher quality care for work-associated carpal tunnel syndrome (CTS) was associated with improved symptoms, functional status, and overall health. We sought to examine whether quality of care is associated with healthcare expenditures or disability. METHODS: Among 343 adults with workers' compensation claims for CTS, we created patient-level aggregate quality scores for underuse (not receiving highly beneficial care) and overuse (receiving care for which risks exceed benefits). We assessed whether each aggregate quality score (0%-100%, 100% = better care) was associated with healthcare expenditures (18-mo expenditures, any anticipated need for future expenditures) or disability (days on temporary disability, permanent impairment rating at 18 mo). RESULTS: Mean aggregate quality scores were 77.8% (standard deviation [SD] 16.5%) for underuse and 89.2% (SD 11.0%) for overuse. An underuse score of 100% was associated with higher risk-adjusted 18-mo expenditures ($3672; 95% confidence interval [CI] $324 to $7021) but not with future expenditures (-0.07 percentage points; 95% CI -0.48 to 0.34), relative to a score of 0%. An overuse score of 100% was associated with lower 18-mo expenditures (-$4549, 95% CI -$8792 to -$306) and a modestly lower likelihood of future expenditures (-0.62 percentage points, 95% CI -1.23 to -0.02). Quality of care was not associated with disability. DISCUSSION: Improving quality of care could increase or lower short-term healthcare expenditures, depending on how often care is currently underused or overused. Future research is needed on quality of care in varied workers' compensation contexts, as well as effective and economical strategies for improving quality.

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma.

BACKGROUND: The immunostimulatory monoclonal antibody elotuzumab plus lenalidomide and dexamethasone has been shown to be effective in patients with relapsed or refractory multiple myeloma. The immunomodulatory agent pomalidomide plus dexamethasone has been shown to be effective in patients with multiple myeloma that is refractory to lenalidomide and a proteasome inhibitor. METHODS: Patients with multiple myeloma that was refractory or relapsed and refractory to lenalidomide and a proteasome inhibitor were randomly assigned to receive elotuzumab plus pomalidomide and dexamethasone (elotuzumab group) or pomalidomide and dexamethasone alone (control group). The primary end point was investigator-assessed progression-free survival. RESULTS: A total of 117 patients were randomly assigned to the elotuzumab group (60 patients) or the control group (57 patients). After a minimum follow-up period of 9.1 months, the median progression-free survival was 10.3 months in the elotuzumab group and 4.7 months in the control group. The hazard ratio for disease progression or death in the elotuzumab group as compared with the control group was 0.54 (95% confidence interval [CI], 0.34 to 0.86; P=0.008). The overall response rate was 53% in the elotuzumab group as compared with 26% in the control group (odds ratio, 3.25; 95% CI, 1.49 to 7.11). The most common grade 3 or 4 adverse events were neutropenia (13% in the elotuzumab group vs. 27% in the control group), anemia (10% vs. 20%), and hyperglycemia (8% vs. 7%). A total of 65% of the patients in each group had infections. Infusion reactions occurred in 3 patients (5%) in the elotuzumab group. CONCLUSIONS: Among patients with multiple myeloma in whom treatment with lenalidomide and a proteasome inhibitor had failed, the risk of progression or death was significantly lower among those who received elotuzumab plus pomalidomide and dexamethasone than among those who received pomalidomide plus dexamethasone alone. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-3 ClinicalTrials.gov number, NCT02654132 .).

Pulmonary artery aneurysm associated with a nonstenotic bicuspid pulmonic valve: A role for genetics?

BACKGROUND: Bicuspid pulmonic valves are quite uncommon, being described in only 0.1% of donor's hearts, while pulmonary artery aneurysms (PAAs) are even rarer, having been found in 8 out of 109,571 autopsies. This rarity makes it difficult to characterize the relationship between them. MATERIALS AND METHODS: We describe the case of a 66-year-old female who was found to have a bicuspid pulmonic valve and PAA (5.1 cm) on imaging by her cardiologist. DISCUSSION AND CONCLUSION: This case raises the question of whether the association between bicuspid semilunar valve disease and vascular wall anomalies is more genetic or hemodynamic. Even on the aortic side, despite the robust association between bicuspid aortic valves and thoracic aortic aneurysms, the mechanism still remains unclear. In our patient there was no significant gradient across the bicuspid pulmonic valve, suggesting that hemodynamics are not the primum mobile of this association.

Stentectomy for LAD "full metal jacket" with in-stent restenosis: How to do it.

We report our technique for the surgical revascularization of symptomatic severe in-stent restenosis of a "full metal jacket" (≥60 mm overlapping stents) of the left anterior descending coronary artery without suitable distal targets: on-pump cardioplegic-arrest stent removal (stentectomy) with endarterectomy and skeletonized left internal mammary artery onlay patch reconstruction. We also describe our follow-up protocol, including antiplatelet/anticoagulation and angiography. With proper patient selection, multidisciplinary collaboration, and surgical expertise, this advanced coronary procedure can be beneficial to a growing population of patients otherwise deemed to be untreatable.

Optimizing Graft Extraction From the Femoral Condyle for Fresh Osteochondral Allograft Transplantation in Treating Osteochondritis Dissecans of the Capitellum: Best Fit Based on Radius of Curvature.

BACKGROUND: Osteochondritis dissecans (OCD) of the capitellum is a common cause of pain and dysfunction in adolescents that engage in repetitive elbow loading. For large, unstable lesions fresh osteochondral allograft transplantation (FOCAT) from the femoral condyle has been described as an effective treatment. Current practice involves significant guesswork in obtaining an appropriately sized graft, with anatomic variations resulting in poor graft fit. No studies currently exist that analyze and identify the best distal femur FOCAT graft site to repair OCD lesions of the capitellum based on the radius of curvature (ROC) and simulated matching. METHODS: Computed tomography scans of the elbow were used to estimate the subchondral bone ROC of capitella in adolescents aged 11 to 21 years. The capitellar location used corresponds to the most commonly reported site of OCD lesions in the elbow. Computed tomography scans of the lower extremity were used to estimate the subchondral bone ROC of 4 potential donor femoral condyle grafts. ROC from distinct regions at the posterior section of both the medial and lateral femoral condyles were measured: 2 areas representing 10 mm grafts from the center (MC1 and LC1), and 2 areas estimating 10 mm grafts posterior and adjacent to the physeal scar (MC2 and LC2). Intraobserver and interobserver reliability measurements were preformed to corroborate precision and validate the method. RESULTS: The mean ROC of healthy subchondral bone at the region of the capitellum were OCD lesions most commonly occur was 9.79±1.39 mm. The mean ROC of MC1 was 18.61±2.26 mm. The average ROC of the MC2 was 15.23±1.43 mm. The average ROC of LC1 was 16.47±1.34 mm. The average ROC of LC2 was 18.19±3.09 mm. After 15,000 simulated condyle-to-capitellar site matchings based on these measurements, a good fit graft was achieved at a frequency of 15%. DISCUSSION: No site measured from the femoral condyle demonstrated a subchondral ROC that exactly matched the subchondral ROC of the capitellum at the center location where OCD lesions most commonly occur; of the locations measured, a 10 mm section from MC2 demonstrated the closest match. On the basis of this analysis, extracting a graft from MC2 has the potential to further optimize FOCAT fit to the capitellum. LEVEL OF EVIDENCE: Level III.

Therapist Strategies for Managing Midtreatment Problems in Evidence-based Interventions in Community Settings.

The National Institute of Health has made it a priority to identify, develop, and refine strategies to disseminate and implement effective interventions (National Institute of Health, 2015). This study examined qualitative reports of the strategies therapists used to manage common implementation problems they encountered during midtreatment in Multisystemic Therapy® (MST) and Functional Family Therapy (FFT), two widely disseminated evidence- and family-based treatments for substance abusing and delinquent adolescents. Experienced therapists from dissemination sites across the U.S. described cases in which they encountered midtreatment problems they perceived as serious threats to treatment success. They indicated why each case terminated and rated the outcome of the case. Qualitative analyses examined 16 treatment failures and then 16 treatment successes to identify contextual obstacles that accompanied the problems therapists identified, along with strategies they reported using with families that ultimately succeeded or failed. Therapists reported that midtreatment problems were often embedded in additional related difficulties and that they employed multiple relationship techniques and process-focused strategies to try to resolve these problems. For the most part, therapists described obstacles and strategies for successful and unsuccessful families in similar ways. Patterns of themes and subthemes suggested, however, that therapists in successful cases may be more likely to report "on-script" strategies and therapists in unsuccessful cases may describe more "off-script" strategies as well as more generic relationship building and advice-giving strategies.

Los Institutos Nacionales de Salud (NIH, por sus siglas en inglés) han priorizado la detección, el desarrollo y la perfección de estrategias para difundir e implementar intervenciones eficaces (National Institute of Health, 2015). Este estudio analizó los informes cualitativos de las estrategias que usaron los terapeutas para manejar los problemas comunes de implementación que encontraron durante la mitad del tratamiento en la terapia multisistémica (Multisystemic Therapy® , MST) y en la terapia familiar funcional (Functional Family Therapy, FFT), dos tratamientos factuales y basados en la familia ampliamente difundidos para adolescentes con problemas de delincuencia y de abuso de sustancias. Un grupo de terapeutas experimentados de centros de difusión de todo Estados Unidos describió casos en los cuales encontraron problemas en la mitad del tratamiento que ellos percibieron como amenazas graves para el éxito del tratamiento. Estos terapeutas indicaron por qué cada caso terminó y calificaron el resultado del caso. Los análisis cualitativos analizaron 16 fallas del tratamiento y luego 16 aciertos del tratamiento para detectar obstáculos contextuales que acompañaban a los problemas mencionados por los terapeutas, junto con estrategias que informaron haber usado con familias y que finalmente fueron satisfactorias o fallaron. Los terapeutas informaron que los problemas en la mitad del tratamiento generalmente formaban parte de otras dificultades relacionadas y que ellos emplearon varias técnicas relacionales y estrategias centradas en los procesos para intentar resolver estos problemas. En su mayoría, los terapeutas describieron los obstáculos y las estrategias utilizadas con las familias favorables y con las desfavorables de maneras similares. Sin embargo, los patrones de temas y subtemas indicaron que los terapeutas de los casos favorables pueden ser más propensos a informar estrategias "dentro del libreto" y que los terapeutas de los casos desfavorables pueden describir más estrategias "fuera del libreto", así como estrategias más genéricas de construcción de relaciones y de asesoramiento.

The quality of electrodiagnostic tests for carpal tunnel syndrome: Implications for surgery, outcomes, and expenditures.

INTRODUCTION: The quality of electrodiagnostic tests may influence treatment decisions, particularly regarding surgery, affecting health outcomes and health-care expenditures. METHODS: We evaluated test quality among 338 adults with workers' compensation claims for carpal tunnel syndrome. Using simulations, we examined how it influences the appropriateness of surgery. Using regression, we evaluated associations with symptoms and functional limitations (Boston Carpal Tunnel Questionnaire), overall health (12-item Short Form Health Survey version 2), actual receipt of surgery, and expenditures. RESULTS: In simulations, suboptimal quality tests rendered surgery inappropriate for 99 of 309 patients (+32 percentage points). In regression analyses, patients with the highest quality tests had larger declines in symptoms (-0.50 point; 95% confidence interval [CI], -0.89 to -0.12) and functional impairment (-0.42 point; 95% CI, -0.78 to -0.06) than patients with the lowest quality tests. Test quality was not associated with overall health, actual receipt of surgery, or expenditures. DISCUSSION: Test quality is pivotal to determining surgical appropriateness and associated with meaningful differences in symptoms and function.

Quality of electrodiagnostic testing for carpal tunnel syndrome: adherence to quality measures.

INTRODUCTION: Research has shown that quality of health-care services is often suboptimal. Little is known about the quality of electrodiagnostic testing. METHODS: We prospectively recruited 477 adults with workers' compensation claims for carpal tunnel syndrome (CTS) from 30 occupational health clinics and evaluated whether electrodiagnostic testing adhered to five process-oriented quality measures. RESULTS: Among patients who had surgery for CTS, nearly all underwent recommended preoperative electrodiagnostic testing (measure #1, 170 of 174, 97.7%). Most electrodiagnostic tests included essential components (measure #2, 295 of 379, 77.8%). However, few reports documented skin temperature (measure #3, 93 of 379, 24.5%) and criteria were seldom met for interpreting test findings as consistent with CTS (measure #4, 41 of 284, 14.4%) or "severe" CTS (measure #5, 8 of 46, 17.4%). DISCUSSION: Most patients underwent testing before surgery, but test quality was often suboptimal. This work lays the groundwork for future efforts to monitor and improve the quality of electrodiagnostic testing for CTS.

Robust estimation of the causal effect of time-varying neighborhood factors on health outcomes.

The fundamental difficulty of establishing causal relationships between an exposure and an outcome in observational data involves disentangling causality from confounding factors. This problem underlies much of neighborhoods research, which abounds with studies that consider associations between neighborhood characteristics and health outcomes in longitudinal data. Such analyses are confounded by selection issues; individuals with above average health outcomes (or associated characteristics) may self-select into advantaged neighborhoods. Techniques commonly used to assess causal inferences in observational longitudinal data, such as inverse probability of treatment weighting (IPTW), may be inappropriate in neighborhoods data due to unique characteristics of such data. We advance the IPTW toolkit by introducing a procedure based on a multivariate kernel density function which is more appropriate for neighborhoods data. The proposed weighting method is applied in conjunction with a marginal structural model. Our empirical analyses use longitudinal data from the Health and Retirement Study; our exposure of interest is an index of neighborhood socioeconomic status (NSES), and we examine its influence on cognitive function. Our findings illustrate the importance of the choice of method for IPTW-the comparison weighting methods provide poor balance across the set of covariates (which is not the case for our preferred procedure) and yield misleading results when applied in the outcomes models. The utility of the multivariate kernel is also validated via simulation. In addition, our findings emphasize the importance of IPTW-controlling for covariates within a regression without IPTW indicates that NSES affects cognition, whereas IPTW-weighted models fail to show a statistically significant effect.

Characteristics and considerations for children with ankyloglossia undergoing frenulectomy for dysphagia and aspiration.

OBJECTIVE: The purpose of this study is to analyze the basic demographics of patients who underwent frenulectomy at our institution as well as additional considerations regarding age, location of procedure, and possible effects on aspiration. METHODS: A retrospective chart review was performed based on CPT codes for frenulectomy and basic demographic data was collected. Other information such as presenting symptoms, type of ankyloglossia, location of the procedure, and modified barium swallow study (MBSS) information were also obtained. RESULTS: A total of 226 (66.4% male) patients underwent frenulectomy in the study time frame. Younger patients underwent frenulectomy for feeding symptoms (average age 6.5 months) and older children typically presented with speech related symptoms (average age 3.8 years). Of patients who had MBSS before and after the procedure, 5/11 (43%) had improvement of their aspiration after frenulectomy. CONCLUSIONS: Symptomatic ankyloglossia is more common in boys. Two age groups typically present for frenulectomy, infants for feeding difficulties and toddlers/preschoolers for speech related difficulties. Children with aspiration may benefit from frenulectomy, though aspiration is unlikely to resolve if other comorbidities are present. Proper evaluation and documentation of anatomy and functional tongue movement is important for future studies and decision-making regarding frenulectomy.

Evaluating Supervision Models in Functional Family Therapy: Does Adding Observation Enhance Outcomes?

This study examined the effects of observation-based supervision Building Outcomes with Observation-Based Supervision of Therapy (BOOST therapists = 26, families = 105), versus supervision as usual (SAU therapists = 21, families = 59) on (a) youth externalizing behavior problems and (b) the moderating effects of changes in family functioning on youth externalizing behaviors for adolescents receiving Functional Family Therapy (FFT). Exploratory analyses examined the impact of supervision conditions on youth internalizing problems. In 8 community agencies, experienced FFT therapists (M = 1.4 years) received either BOOST or SAU supervision in a quasi-experimental design. Male (59%) or female (41%) adolescents were referred for the treatment of behavior problems (e.g., delinquency, substance use). Clients were Hispanic (62%), African American (19%), Non-Hispanic White (12%), or Other (7%) ethnic/racial origins. Therapists (female, 77%) were Hispanic 45%, African American (19%), White Non-Hispanic (30%), or other (4%) ethnic/racial backgrounds. Analyses controlled for the presence or absence of clinically elevated symptoms on outcome variables. Clinical outcomes were measured at baseline, 5 months, and 12 months after treatment initiation. Clients with externalizing behavior above clinical thresholds had significantly greater reductions in problem behaviors in the BOOST versus the SAU conditions. Clients below thresholds did not respond differentially to conditions. Supervisors in BOOST had more experience with the FFT model; as such, the observed results may be a result of supervisor experience. The BOOST supervision was associated with improved outcomes on problem behaviors that were above clinical thresholds. The findings demonstrate the importance of addressing client case mix in implementation studies in natural environments.

Este estudio examinó los efectos de la supervisión basada en la observación (terapeutas de BOOST = 26, familias = 105) frente a la supervisión habitual (terapeutas de SAU = 21, familias = 59) en (a) la externalización de problemas de conducta en los jóvenes y (b) los efectos moderadores de los cambios en el funcionamiento familiar sobre la externalización de conductas de los jóvenes en el caso de adolescentes que reciben terapia familiar funcional (FFT). Los análisis exploratorios analizaron el efecto de las condiciones de la supervisión en la internalización de problemas de los jóvenes. En 8 agencias comunitarias, terapeutas experimentados en FFT (M = 1,4 años) recibieron supervisión BOOST o SAU en un diseño cuasiexperimental. Se derivó a adolescentes masculinos (59%) o femeninos (41%) para el tratamiento de problemas conductuales (p. ej.: delincuencia, consumo de sustancias). Los pacientes eran hispanos (62%), afroamericanos (19%), blancos no hispanos (12%) o de otros orígenes étnicos o raciales (7%). Los terapeutas (femeninos, 77%) eran hispanos 45%, afroamericanos (19%), blancos no hispanos (30%) o de otros orígenes étnicos o raciales (4%). Los análisis tuvieron en cuenta la presencia o la ausencia de síntomas clínicamente elevados en los criterios de valoración. Se midieron las variables clínicas al inicio, a los 5 meses y 12 meses después del inicio del tratamiento. Resultados: Los pacientes con externalización del comportamiento por encima de los límites clínicos tuvieron reducciones considerablemente mayores de los comportamientos problemáticos en las condiciones de BOOST frente a las de SAU. Los pacientes por debajo de los límites no respondieron de forma diferencial a las condiciones. Los supervisores de BOOST tenían más experiencia con el modelo de FFT; por lo tanto, los resultados observados pueden ser el resultado de la experiencia de los supervisores. La supervisión BOOST estuvo asociada con mejores resultados en los comportamientos problemáticos que estaban por encima de los límites clínicos. Los resultados demuestran la importancia de abordar la variedad de casos de pacientes en la implementación de estudios en ambientes naturales.

Midtreatment Problems Implementing Evidence-based Interventions in Community Settings.

Multisystemic Therapy® (MST) and Functional Family Therapy (FFT) are two widely disseminated evidence-based family-based treatments for substance abusing and delinquent adolescents. This mixed-method study examined common implementation problems in midtreatment in MST and FFT. A convenience sample of experienced therapists (20 MST, 20 FFT) and supervisors (10 MST, 10 FFT) from dissemination sites across the United States participated in semistructured telephone interviews. Participants identified retrospectively serious midtreatment process problems they perceived as threats to treatment success. Coders extracted descriptions of problems from interview transcripts and coded them into 12 categories that fell into five major themes: engaging families in treatment; difficulties implementing strategies; family relational and communication problems; complications external to therapy; and youth problem behavior. Analyses examined caregiver, therapist, and youth variables as predictors of these common midtreatment problems and whether treatment outcomes varied depending on the type of problem, therapy model, and race/ethnic match of therapist and family. MST and FFT therapists and supervisors identified many similar problems. There were, however, model-specific differences consistent with differing features of the models (e.g., FFT participants identified more family relational problems and fewer follow-through problems than their MST counterparts). Results underscore the need to consider both common and specific factors in treatment process.

La terapia multisistémica (Multisystemic Therapy®, MST) y la terapia familiar funcional (Functional Family Therapy, FFT) son dos tratamientos factuales familiares ampliamente difundidos para adolescentes con problemas de abuso de sustancias y delincuencia. Este estudio de métodos combinados analizó los problemas de implementación comunes a mediados del tratamiento en la MST y la FFT. Una muestra de conveniencia de terapeutas experimentados (20 MST, 20 FFT) y supervisores (10 MST, 10 FFT) de centros de difusión de todo EE. UU. participaron en entrevistas telefónicas semiestructuradas. Los participantes reconocieron retrospectivamente graves problemas en el proceso a mediados del tratamiento que percibieron como amenazas para el éxito del tratamiento. Los codificadores extrajeron las descripciones de problemas de las transcripciones de las entrevistas y los codificaron en 12 categorías que comprendían cinco temas principales: interés de las familias por el tratamiento; dificultades para implementar estrategias; problemas de comunicación y relacionales con la familia; complicaciones ajenas a la terapia; y comportamiento problemático de los jóvenes. Los análisis examinaron las variables de cuidador, terapeuta y joven como predictores de estos problemas comunes a mediados del tratamiento y si los resultados del tratamiento variaron según el tipo de problema, el modelo de terapia y la coincidencia étnica/racial entre el terapeuta y la familia. Los terapeutas y los supervisores de la MST y la FFT detectaron varios problemas similares. Sin embargo, hubo diferencias específicas de los modelos que coincidieron con las distintas características de los modelos (p. ej.: los participantes de la FFT reconocieron más problemas de relaciones familiares y menos problemas para terminar el tratamiento que sus homólogos de la MST). Los resultados subrayan las necesidad de tener en cuenta tanto los factores comunes como específicos del proceso de tratamiento.

Juvenile Justice Risk Factors and Functional Family Therapy Fidelity on Felony Recidivism.

Families (n = 5,884) received Functional Family Therapy (FFT) provided as part of court-ordered probation services by 11 community sites throughout Florida. Sites provided home-based FFT to families with male (72%) or female (28%) delinquent youth. Juvenile justice courts referred clients to these services in an effort to redirect them away from incarceration. Clients were Hispanic (18%), Black (41%), and White Non-Hispanic (36%), while therapists (female, 79%) were of Hispanic (28%), Black (20%), and White Non-Hispanic (50%) ethnic/racial origins. Analyses of clients' pretreatment recidivism risk and therapist's caseload of risky clients demonstrated that both individual and treatment site case-mix of client criminal risk levels were associated with higher adjudicated felony recidivism. Furthermore, clinical process indicators suggest that therapists with larger rather than smaller caseloads of high-risk clients provided treatment with greater fidelity. Results suggest that experience in working with challenging clients is critical for achieving fidelity with these cases.

Elotuzumab monotherapy in patients with smouldering multiple myeloma: a phase 2 study.

Smouldering multiple myeloma (SMM) is associated with increased risk of progression to multiple myeloma within 2 years, with no approved treatments. Elotuzumab has been shown to promote natural killer (NK) cell stimulation and antibody-dependent cellular cytotoxicity (ADCC) in vitro. CD56dim (CD56dim /CD16+ /CD3- /CD45+ ) NK cells represent the primary subset responsible for elotuzumab-induced ADCC. In this phase II, non-randomized study (NCT01441973), patients with SMM received elotuzumab 20 mg/kg intravenously (cycle 1: days 1, 8; monthly thereafter) or 10 mg/kg (cycles 1, 2: weekly; every 2 weeks thereafter). The primary endpoint was the relationship between baseline proportion of bone marrow-derived CD56dim NK cells and maximal M protein reduction; secondary endpoints included overall response rate (ORR) and progression-free survival (PFS). Fifteen patients received 20 mg/kg and 16 received 10 mg/kg; combined data arepresented. At database lock (DBL, September 2014), no association was found between baseline CD56dim NK cell proportion and maximal M protein reduction. With minimum 28 months' follow-up (DBL: January 2016), ORR (90% CI) was 10% (2·7-23·2) and 2-year PFS rate was 69% (52-81%). Upper respiratory tract infections occurred in 18/31 (58%) patients. Four (13%) patients experienced infusion reactions, all grade 1-2. Elotuzumab plus lenalidomide/dexamethasone is under investigation for SMM.

Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM.

In this proof-of-concept, open-label, phase 2 study, patients with relapsed/refractory multiple myeloma (RRMM) received elotuzumab with bortezomib and dexamethasone (EBd) or bortezomib and dexamethasone (Bd) until disease progression/unacceptable toxicity. Primary endpoint was progression-free survival (PFS); secondary/exploratory endpoints included overall response rate (ORR) and overall survival (OS). Two-sided 0.30 significance level was specified (80% power, 103 events) to detect hazard ratio (HR) of 0.69. Efficacy and safety analyses were performed on all randomized patients and all treated patients, respectively. Of 152 randomized patients (77 EBd, 75 Bd), 150 were treated (75 EBd, 75 Bd). PFS was greater with EBd vs Bd (HR, 0.72; 70% confidence interval [CI], 0.59-0.88; stratified log-rank P = .09); median PFS was longer with EBd (9.7 months) vs Bd (6.9 months). In an updated analysis, EBd-treated patients homozygous for the high-affinity FcγRIIIa allele had median PFS of 22.3 months vs 9.8 months in EBd-treated patients homozygous for the low-affinity allele. ORR was 66% (EBd) vs 63% (Bd). Very good partial response or better occurred in 36% of patients (EBd) vs 27% (Bd). Early OS results, based on 40 deaths, revealed an HR of 0.61 (70% CI, 0.43-0.85). To date, 60 deaths have occurred (28 EBd, 32 Bd). No additional clinically significant adverse events occurred with EBd vs Bd. Grade 1/2 infusion reaction rate was low (5% EBd) and mitigated with premedication. In patients with RRMM, elotuzumab, an immunostimulatory antibody, appears to provide clinical benefit without added clinically significant toxicity when combined with Bd vs Bd alone. Registered to ClinicalTrials.gov as NCT01478048.

Quality of care and patient-reported outcomes in carpal tunnel syndrome: A prospective observational study.

INTRODUCTION: Higher quality care for carpal tunnel syndrome (CTS) may be associated with better outcomes. METHODS: This prospective observational study recruited adults diagnosed with CTS from 30 occupational health centers, evaluated physicians' adherence to recommended care processes, and assessed results of the Boston Carpal Tunnel Questionnaire (BCTQ) and Short Form Health Survey version 2 (SF-12v2) at recruitment and at 18 months. RESULTS: Among 343 individuals, receiving better care (80th vs. 20th percentile for adherence) was associated with greater improvements in BCTQ Symptom Severity scores (-0.18, 95% confidence interval [CI] -0.32 to -0.05), BCTQ Functional Status scores (-0.21, 95% CI -0.34 to -0.08), and SF12-v2 Physical Component scores (1.75, 95% CI 0.33-3.16). Symptoms improved more when physicians assessed and managed activity, patients underwent necessary surgery, and employers adjusted job tasks. DISCUSSION: Efforts should be made to ensure that patients with CTS receive essential care processes including necessary surgery and activity assessment and management. Muscle Nerve 57: 896-904, 2018.

Methods for determining key components in a mathematical model for tumor-immune dynamics in multiple myeloma.

In this work, we analyze a mathematical model we introduced previously for the dynamics of multiple myeloma and the immune system. We focus on four main aspects: (1) obtaining and justifying ranges and values for all parameters in the model; (2) determining a subset of parameters to which the model is most sensitive; (3) determining which parameters in this subset can be uniquely estimated given certain types of data; and (4) exploring the model numerically. Using global sensitivity analysis techniques, we found that the model is most sensitive to certain growth, loss, and efficacy parameters. This analysis provides the foundation for a future application of the model: prediction of optimal combination regimens in patients with multiple myeloma.