Improving concussion education: consensus from the NCAA-Department of Defense Mind Matters Research & Education Grand Challenge
Early disclosure of possible concussive symptoms has the potential to improve concussion-related clinical outcomes. The objective of the present consensus process was to provide useful and feasible recommendations for collegiate athletic departments and military service academy leaders about how to increase concussion symptom disclosure in their setting. Consensus was obtained using a modified Delphi process. Participants in the consensus process were grant awardees from the National Collegiate Athletic Association and Department of Defense Mind Matters Research & Education Grand Challenge and a multidisciplinary group of stakeholders from collegiate athletics and military service academies. The process included a combination of in-person meetings and anonymous online voting on iteratively modified recommendations for approaches to improve concussion symptom disclosure. Recommendations were rated in terms of their utility and feasibility in collegiate athletic and military service academy settings with a priori thresholds for retaining, discarding and revising statements. A total of 17 recommendations met thresholds for utility and feasibility and are grouped for discussion in five domains: (1) content of concussion education for athletes and military service academy cadets, (2) dissemination and implementation of concussion education for athletes and military service academy cadets, (3) other stakeholder concussion education, (4) team and unit-level processes and (5) organisational processes. Collectively, these recommendations provide a path forward for athletics departments and military service academies in terms of the behavioural health supports and institutional processes that are needed to increase early and honest disclosure of concussion symptoms and ultimately to improve clinical care outcomes.
Risk Factors for Graft-versus-Host Disease in Haploidentical Hematopoietic Cell Transplantation Using Post-Transplant Cyclophosphamide
Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with relatively low incidence of GVHD. Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haploHCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with AML, ALL, MDS, or CML who underwent PTCy-based haploHCT (2013-2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced intensity (RIC) conditioning and bone marrow (BM) or peripheral blood (PB) graft source. 646 patients were identified (MA-BMâ€¯=â€¯79, MA-PBâ€¯=â€¯183, RIC-BMâ€¯=â€¯192, RIC-PBâ€¯=â€¯192). The incidence of grade 2-4 aGVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (p=0.002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (p<0.001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2-4 acute GVHD; however, older donor age (30-49 versus <29 years) was significantly associated with higher rates of grade 2-4 acute GVHD (HR 1.53, 95% CI 1.11-2.12, p=0.01). In contrast, PB compared to BM as a stem cell source was a significant risk factor for the development of chronic GVHD (HR 1.70, 95% CI 1.11-2.62, p=0.01) in the RIC setting. There were no differences in relapse or overall survival between groups. Donor age and graft source are risk factors for acute and chronic GVHD, respectively, after PTCy-based haploHCT.Â Our results indicate that in RIC haploHCT, the risk of chronic GVHD is higher with PB stem cells, without any difference in relapse or overall survival.
Adjuvant endocrine therapy for breast cancer patients: impact of a health system outreach program to improve adherence
PURPOSE/OBJECTIVE:Reports suggest that up to 50% of women with hormone receptor-positive (HR+) breast cancer (BC) do not complete the recommended 5Â years of adjuvant endocrine therapy (AET). We examined the impact of an outreach program at Kaiser Permanente Northern California (KPNC) on adherence and discontinuation of AET among patients who initiated AET. METHODS:We assembled a retrospective cohort of all KPNC patients diagnosed with HR+, stage I-III BC initiating AET before (nâ€‰=â€‰4287) and after (nâ€‰=â€‰3580) implementation of the outreach program. We compared adherence proportions and discontinuation rates before and after program implementation, both crude and adjusted for age, race/ethnicity, education, income, and stage. We conducted a pooled analysis of data from six Cancer Research Network (CRN) sites that had not implemented programs for improving AET adherence, using identical methods and time periods, to assess possible secular trends. RESULTS:In the pre-outreach period, estimated adherence in years 1, 2, and 3 following AET initiation was 75.2%, 71.0%, and 67.3%; following the outreach program, the estimates were 79.4%, 75.6%, and 72.2% (p-valuesâ€‰<â€‰.0001 for pairwise comparisons). Results were comparable after adjusting for clinical and demographic factors. The estimated cumulative incidence of discontinuation was 0.22 (0.21-0.24) and 0.18 (0.17-0.19) at 3 years for pre- and post-outreach groups (p-valueâ€‰<â€‰.0001). We found no evidence of an increase in adherence between the study periods at the CRN sites with no AET adherence program. CONCLUSION/CONCLUSIONS:Adherence and discontinuation after AET initiation improved modestly following implementation of the outreach program.
NAM Therapy-Evidence-Based Results [Letter]
Many orthodontists working on patients with cleft lip and palate (CLP) have shown great enthusiasm for presurgical infant orthopedics (PSIO) to improve surgical outcomes with minimal intervention. Even though every clinician aims to use the best treatment modality for their patients, PSIO effects can be confounded by surgical type and timing of the primary repair, as is discussed in many studies. In such cases, one should be cautious when evaluating the particular outcomes for patients with CLP since it is difficult to differentiate the sole effect of an individual surgical or orthodontic intervention. As with any treatment methodology, nasoalveolar molding (NAM) has both benefits and limitations. Commonly cited concerns with NAM, and PSIO in general, include increased cost, increased burden of care, and a negative impact on maxillary growth. However, NAM cannot be deemed as having apparent long-term negative or positive effects on skeletal or soft tissue facial growth, based on previous studies. A review of the literature suggests that NAM does not alter skeletal facial growth when compared with the samples that did not receive PSIO. Nevertheless, the published studies on NAM show evidence of benefits to the patient, caregivers, the surgeon, and society. These benefits include documented reduction in severity of the cleft deformity prior to surgery and as a consequence improved surgical outcomes, reduced burden of care on the care givers, reduction in the need for revision surgery, and consequent reduced overall cost of care to the patient and society.
An Artificial Intelligence Algorithm to Identify Documented Symptoms in Patients with Heart Failure who Received Cardiac Resynchronization Therapy [Meeting Abstract]
WIPI1 is a conserved mediator of right ventricular failure
Right ventricular dysfunction is highly prevalent across cardiopulmonary diseases and independently predicts death in both heart failure (HF) and pulmonary hypertension (PH). Progression towards right ventricular failure (RVF) can occur in spite of optimal medical treatment of HF or PH, highlighting current insufficient understanding of RVF molecular pathophysiology. To identify molecular mechanisms that may distinctly underlie RVF, we investigated the cardiac ventricular transcriptome of advanced HF patients, with and without RVF. Using an integrated systems genomic and functional biology approach, we identified an RVF-specific gene module, for which WIPI1 served as a hub and HSPB6 and MAP4 as drivers, and confirmed the ventricular specificity of Wipi1, Hspb6, and Map4 transcriptional changes in adult murine models of pressure overload induced RV- versus LV- failure. We uncovered a shift towards non-canonical autophagy in the failing RV that correlated with RV-specific Wipi1 upregulation. In vitro siRNA silencing of Wipi1 in neonatal rat ventricular myocytes limited non-canonical autophagy and blunted aldosterone-induced mitochondrial superoxide levels. Our findings suggest that Wipi1 regulates mitochondrial oxidative signaling and non-canonical autophagy in cardiac myocytes. Together with our human transcriptomic analysis and corroborating studies in an RVF mouse model, these data render Wipi1 a potential target for RV-directed HF therapy.
Time-to-event data with time-varying biomarkers measured only at study entry, with applications to Alzheimer's disease
Relating time-varying biomarkers of Alzheimer's disease to time-to-event using a Cox model is complicated by the fact that Alzheimer's disease biomarkers are sparsely collected, typically only at study entry; this is problematic since Cox regression with time-varying covariates requires observation of the covariate process at all failure times. The analysis might be simplified by using study entry as the time origin and treating the time-varying covariate measured at study entry as a fixed baseline covariate. In this paper, we first derive conditions under which using an incorrect time origin of study entry results in consistent estimation of regression parameters when the time-varying covariate is continuous and fully observed. We then derive conditions under which treating the time-varying covariate as fixed at study entry results in consistent estimation. We provide methods for estimating the regression parameter when a functional form can be assumed for the time-varying biomarker, which is measured only at study entry. We demonstrate our analytical results in a simulation study and apply our methods to data from the Rush Religious Orders Study and Memory and Aging Project and data from the Alzheimer's Disease Neuroimaging Initiative.
Surgical Findings and Outcomes in Premenopausal Breast Cancer Patients Undergoing Oophorectomy: A Multicenter Review From the Society of Gynecologic Surgeons Fellows Pelvic Research Network
STUDY OBJECTIVE:To describe the procedures performed, intra-abdominal findings, and surgical pathology in a cohort of women with premenopausal breast cancer who underwent oopherectomy. DESIGN:Multicenter retrospective chart review (Canadian Task Force classification II-3). SETTING:Nine US academic medical centers participating in the Fellows' Pelvic Research Network (FPRN). PATIENTS:One hundred twenty-seven women with premenopausal breast cancer undergoing oophorectomy between January 2013 and March 2016. INTERVENTION:Surgical castration. MEASUREMENTS AND MAIN RESULTS:The mean patient age was 45.8 years. Fourteen patients (11%) carried a BRCA mutations, and 22 (17%) carried another germline or acquired mutation, including multiple variants of uncertain significance. There was wide variation in surgical approach. Sixty-five patients (51%) underwent pelvic washings, and 43 (35%) underwent concurrent hysterectomy. Other concomitant procedures included midurethral sling placement, appendectomy, and hysteroscopy. Three patients experienced complications (transfusion, wound cellulitis, and vaginal cuff dehiscence). Thirteen patients (10%) had ovarian pathology detected on analysis of the surgical specimen, including metastatic tumor, serous cystadenomas, endometriomas, and Brenner tumor. Eight patients (6%) had Fallopian tube pathology, including 3 serous tubal intraepithelial cancers. Among the 44 uterine specimens, 1 endometrial adenocarcinoma and 1 multifocal endometrial intraepithelial neoplasia were noted. Regarding the entire study population, the number of patients meeting our study criteria and seen by gynecologic surgeons in the FPRN for oophorectomy increased by nearly 400% from 2013 to 2015. CONCLUSION:Since publication of the Suppression of Ovarian Function Trial data, bilateral oophorectomy has been recommended for some women with premenopausal breast cancer to facilitate breast cancer treatment with aromatase inhibitors. These women may be at elevated risk for occult abdominal pathology compared with the general population. Gynecologic surgeons often perform castration oophorectomy in patients with breast cancer as an increasing number of oncologists are using aromatase inhibitors to treat premenopausal breast cancer. Our data suggest that other abdominal/pelvic cancers, precancerous conditions, and previously unrecognized metastatic disease are not uncommon findings in this patient population. Gynecologists serving this patient population may consider a careful abdominal survey, pelvic washings, endometrial sampling, and serial sectioning of fallopian tube specimens for a thorough evaluation.
Activation, self-management, engagement, and retention in behavioral health care: a randomized clinical trial of the DECIDE intervention
IMPORTANCE: Given minority patients' unequal access to quality care, patient activation and self-management strategies have been suggested as a promising approach to improving mental health care. OBJECTIVE: To determine whether the DECIDE (Decide the problem; Explore the questions; Closed or open-ended questions; Identify the who, why, or how of the problem; Direct questions to your health care professional; Enjoy a shared solution) intervention, an educational strategy that teaches patients to ask questions and make collaborative decisions with their health care professional, improves patient activation and self-management, as well as engagement and retention in behavioral health care. DESIGN, SETTING, AND PATIENTS: In this multisite randomized clinical trial performed from February 1, 2009, through October 9, 2011 (date of last follow-up interview), we recruited 647 English- or Spanish-speaking patients 18 to 70 years old from 13 outpatient community mental health clinics across 5 states and 1 US territory. A total of 722 patients were included in analyses of secondary outcomes. INTERVENTIONS: Three DECIDE training sessions delivered by a care manager vs giving patients a brochure on management of behavioral health. MAIN OUTCOMES AND MEASURES: Primary outcomes were patient assessment of activation (Patient Activation Scale) and self-management (Perceived Efficacy in Patient-Physician Interactions). Secondary outcomes included patient engagement (proportion of visits attended of those scheduled) and retention (attending at least 4 visits in the 6 months after the baseline research assessment), collected through medical record review or electronic records. RESULTS: Patients assigned to DECIDE reported significant increases in activation (mean beta = 1.74, SD = 0.58; P = .003) and self-management (mean beta = 2.42, SD = 0.90; P = .008) relative to control patients, but there was no evidence of an effect on engagement or retention in care. CONCLUSIONS AND RELEVANCE: The DECIDE intervention appears to help patients learn to effectively ask questions and participate in decisions about their behavioral health care, but a health care professional component might be needed to augment engagement in care. DECIDE appears to have promise as a strategy for changing the role of minority patients in behavioral health care. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01226329
Single-institution, multidisciplinary experience with surgical resection of primary chest wall sarcomas
INTRODUCTION: Primary chest wall sarcomas are rare mesenchymal tumors and their mainstay of therapy is wide surgical resection. We report our single-institution, multidisciplinary experience with full-thickness resection for primary chest wall sarcomas. METHODS: A retrospective review of our prospectively maintained databases revealed that 51 patients were referred for primary chest wall sarcomas from 1990 to 2009. RESULTS: All patients required resections that included rib and/or sternum. Twenty-nine patients (57%) had extended resections beyond the chest wall. Forty-two patients (82%) required prosthetic reconstruction and 17 patients (33%) had muscle flap coverage. Overall, 51% (26/51) of patients received neoadjuvant therapy. Seventy-three percent (11/15) of high-grade soft tissue sarcomas, 77% (10/13) of high-risk bony sarcomas, and 67% (4/6) of desmoid tumors were treated with induction therapy. Negative margins were obtained in 46 patients (90%). There were no perioperative mortalities. Eight patients (16%) experienced complications. Local recurrence and metastasis was detected in 14 and 23%. Five-year overall and disease-free survivals were 66% and 47%, respectively. Favorable prognostic variables for survival included age =50 years, tumor volume =200 cm, desmoid tumor, bony tumor, chondrosarcoma, and low-grade soft tissue sarcoma. CONCLUSIONS: We report our multidisciplinary experience with primary chest wall sarcomas that included induction therapy in the majority of high-risk soft tissue and bony sarcomas and desmoid tumors. Despite aggressive preoperative treatments, acceptable surgical results with low morbidity and mortality can be achieved. Neoadjuvant systemic therapy may reduce local and distant recurrence and improve overall survival.