The Role of Cytotoxic Therapy with Hematopoietic Stem Cell Transplantation in the Therapy of Acute Lymphoblastic Leukemia in Adults: An Evidence-based Review

AbstractEvidence supporting the role of hematopoietic stem cell transplantation (SCT) in the therapy of acute lymphoblastic leukemia in adults (≥15 years) is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published medical literature and for grading the quality and strength of the evidence, and the strength of the treatment recommendations. Treatment recommendations based on the evidence are presented and were reached unanimously by a panel of acute lymphoblastic leukemia experts. The priority areas of needed future research for adult acute lymphoblastic leukemia are: definition of patients at high risk in first complete remission, beyond Philadelphia chromosome positive; outcomes of SCT in older (>50 years) adults; determination if reduced intensity versus myeloablative conditioning regimens yield an equivalent graft-versus-leukemia effect with reduced toxicity; monitoring of minimal residual disease to achieve disease control before SCT; and the use of cord blood and other alternative sources of stem cells for use in adult SCT recipients

Prison Rape Elimination Act (PREA): Considerations for Policy Review

A policy review guide designed to assist in drafting PREA (Prison Rape Elimination Act) policies for review by the National Institute of Corrections (NIC) is provided. Sections of this document are: purpose; questions to consider -- policy organization, definitions, zero tolerance, staff/offender duty to report, prevention, and investigations (e.g., general, selection and training of investigators, protocols, and aftermath); and list of resources

Statistical Learning Methods to Identify Nonwear Periods From Accelerometer Data

Background: Accelerometers are used to objectively measure movement in free-living individuals. Distinguishing nonwear from sleep and sedentary behavior is important to derive accurate measures of physical activity, sedentary behavior, and sleep. We applied statistical learning approaches to examine their promise in detecting nonwear time and compared the results with commonly used wear time (WT) algorithms. Methods: Fifteen children, aged 4–17, wore an ActiGraph wGT3X- BT monitor on their hip during overnight polysomnography. We applied Hidden Markov Models (HMM) and Gaussian Mixture Models (GMM) to classify states of nonwear and wear in triaxial acceleration data. Performance of methods was compared with WT algorithms across two conditions with differing amounts of consecutive nonwear. Clinical scoring of polysomnography served as the gold standard. Results: When the length of nonwear was less than or equal to WT algorithms’ predefined thresholds for consecutive nonwear time, GMM methods yielded improved classification error, specificity, positive predictive value, and negative predictive value over commonly used algorithms. HMM was superior to one algorithm for sensitivity and negative predictive value. When the length of nonwear was longer, results were mixed, with the commonly used algorithms performing better on some parameters but GMM with the greatest specificity. However, all approached the upper limits of performance for almost all metrics. Conclusions: GMM and HMM demonstrated robust, consistently strong performance across multiple conditions, surpassing or remaining competitive with commonly used WT algorithms which had marked inaccuracy when nonwear time periods were shorter. Of the two statistical learning algorithms, GMM was superior to HMM

Randomized clinical trial of therapeutic music video intervention for resilience outcomes in adolescents/young adults undergoing hematopoietic stem cell transplant: a report from the Children's Oncology Group

BACKGROUND: To reduce the risk of adjustment problems associated with hematopoietic stem cell transplant (HSCT) for adolescents/young adults (AYAs), we examined efficacy of a therapeutic music video (TMV) intervention delivered during the acute phase of HSCT to: 1) increase protective factors of spiritual perspective, social integration, family environment, courageous coping, and hope-derived meaning; 2) decrease risk factors of illness-related distress and defensive coping; and 3) increase outcomes of self-transcendence and resilience. METHODS: This was a multisite randomized, controlled trial (COG-ANUR0631) conducted at 8 Children's Oncology Group sites involving 113 AYAs aged 11-24 years undergoing myeloablative HSCT. Participants, randomized to the TMV or low-dose control (audiobooks) group, completed 6 sessions over 3 weeks with a board-certified music therapist. Variables were based on Haase's Resilience in Illness Model (RIM). Participants completed measures related to latent variables of illness-related distress, social integration, spiritual perspective, family environment, coping, hope-derived meaning, and resilience at baseline (T1), postintervention (T2), and 100 days posttransplant (T3). RESULTS: At T2, the TMV group reported significantly better courageous coping (Effect Size [ES], 0.505; P = .030). At T3, the TMV group reported significantly better social integration (ES, 0.543; P = .028) and family environment (ES, 0.663; P = .008), as well as moderate nonsignificant effect sizes for spiritual perspective (ES, 0.450; P = .071) and self-transcendence (ES, 0.424; P = .088). CONCLUSIONS: The TMV intervention improves positive health outcomes of courageous coping, social integration, and family environment during a high-risk cancer treatment. We recommend the TMV be examined in a broader population of AYAs with high-risk cancers

BUILDING A SUSTAINABLE NETWORK OF DROUGHT COMMUNITIES

The first step in managing large-scale (national) collaborations and networks is to consider and address how a group and a potential partnership may match up (Luther, 2005). To explore this concept and many other collaborative concepts, the National Integrated Drought Information System (NIDIS) hosted a workshop, “Building a Sustainable Network of Drought Communities,” which was facilitated by the National Drought Mitigation Center (NDMC) in Chicago, IL, June 8-9, 2011. The workshop explored current examples of good communication and lessons learned within the realm of drought planning in order to address a future NIDIS Engaging Preparedness Communities (EPC) working group that is solution-focused and collaborative. With the diversity and experience of the participants at this meeting, a wealth of good practices or lessons learned in drought planning, preparedness, and general stakeholder engagement set the pathway for building a sustainable community of drought practitioners. In his opening remarks, NIDIS Director Roger Pulwarty noted that adaptive institutions can show robustness in the following ways: Levels of alertness—monitoring the external world for early warning signs that key assumptions are likely to verify/fail and a commitment to rigorous monitoring of performance; Agility—the ability to react to early warning signs of problems or opportunities; flow of knowledge across components, and to adjust strategies and tactics rapidly to meet changes in the environment; and Alignment—the ability to align the whole organization (and partners) to its mission-policies and practices that give rise to failures/successes. Through an interactive workshop format that used Appreciative Inquiry (framing breakout sessions on success), the group was able to effectively discuss topics such as: • Integrating Planning Efforts • Planning Under Uncertainty • Evaluating, Assessing, and Updating Drought Plans • Leveraging Resources for Risk Management • Implementing Plans and Planning Information • Synthesizing Success Stories and Lessons Learned • Creating a Sustainable Network of Drought Professionals The most common themes resulting from the workshop included: • Importance of networking and collaboration—this is a necessity. Figuring out how to make it seamless is the main goal that the NIDIS EPC Community should foster. Good communication is the key among the drought practitioners and their stakeholders. • Celebrate success—in this future drought network, successes related to drought efforts should be highlighted within the community and to the public. This will help drive future positive interactions and collaborations. It also gives the community a sense of pride. • “Stakeholder Buy-In”—why should stakeholders stay engaged in an ongoing drought community? Especially when there is no drought? Again, good communication and collaborations with other multi-hazard, sustainability, and natural resources planning efforts will help keep drought a priority. • Economic, environmental, and social aspects of planning for drought—these should always be considered. This was a recurrent theme in the workshop. • Planners should not “reinvent the wheel”—planners involved in climate adaptation work can and should reference the best drought planning resources and case studies to help them incorporate drought in their overall planning efforts. • “Have a plan for the plan”—how and who will make it happen? What kind of leadership is needed within the NIDIS EPC community to track its progress and success? • Sharing of resources—as budgets become slimmer, a central location of available resources and the sharing of resources in the area of drought preparedness and mitigation is necessary. Communication regarding these potential resources should also be integrated into this NIDIS EPC community. Since the occurrence of the workshop, several EPC-related activities have taken place, including a webinar in December 2011. This workshop report and additional EPC updates will be placed on the U.S. Drought portal (www.drought.gov). Currently, the American Planning Association (APA), NIDIS and the NDMC are collaborating to produce a Planning Advisory Service (PAS) Report to connect drought mitigation resources with the planning practices of local, regional, tribal and state governments. This builds on the work of the APA’s Hazard Planning Center, which produced a similar PAS Report (sponsored by FEMA) on how to integrate multi-hazard planning into planning practices. In May 2012: The APA’s drought planning project webpage went live and can be found at: http://www.planning.org/research/drought/index.ht

TNF-Receptor Inhibitor Therapy for the Treatment of Children with Idiopathic Pneumonia Syndrome. A Joint Pediatric Blood and Marrow Transplant Consortium and Children's Oncology Group Study (ASCT0521)

AbstractIdiopathic pneumonia syndrome (IPS) is an acute, noninfectious lung disorder associated with high morbidity and mortality after hematopoietic cell transplantation. Previous studies have suggested a role for TNFα in the pathogenesis of IPS. We report a multicenter phase II trial investigating a soluble TNF-binding protein, etanercept (Enbrel, Amgen, Thousand Oaks, CA), for the treatment of pediatric patients with IPS. Eligible patients were < 18 years old, within 120 days after transplantation, and with radiographic evidence of a diffuse pneumonitis. All patients underwent a pretherapy broncho-alveolor lavage (BAL) to establish the diagnosis of IPS. Systemic corticosteroids (2.0 mg/kg/day) plus etanercept (.4 mg/kg twice weekly × 8 doses) were administered. Response was defined as survival and discontinuation of supplemental oxygen support by day 28 of study. Thirty-nine patients (median age, 11 years; range, 1 to 17) were enrolled, with 11 of 39 patients nonevaluable because of identification of pathogens from their pretherapy BAL. In the remaining 28 patients, the median fraction of inspired oxygen at study entry was 45%, with 17 of 28 requiring mechanical ventilation. Complete responses were seen in 20 (71%) patients, with a median time to response of 10 days (range, 1 to 24). Response rates were higher for patients not requiring mechanical ventilation at study entry (100% versus 53%, P = .01). Overall survival at 28 days and 1 year after therapy were 89% (95% confidence interval [CI], 70% to 96%) and 63% (95% CI, 42% to 79%), respectively. Plasma levels of proinflammatory cytokines were significantly increased at onset of therapy, subsequently decreasing in responding patients. The addition of etanercept to high-dose corticosteroids was associated with high response rates and survival in children with IPS

Adaptation and qualitative evaluation of the BETTER intervention for chronic disease prevention and screening by public health nurses in low income neighbourhoods : views of community residents

The adaptation phase is one component of a study funded as a grant proposal entitled 'Advancing Cancer Prevention Among Deprived Neighbourhoods' by the Canadian Cancer Society Research Institute grant #704042 and by the Canadian Institutes of Health Research Institute of Cancer grant OCP #145450. Aisha Lofters is supported by a CIHR New Investigator Award, as a Clinician Scientist by the Department of Family and Community Medicine, University of Toronto, and as Chair in Implementation Science at the Peter Gilgan Centre for Women’s Cancers at Women’s College Hospital in partnership with the Canadian Cancer Society. Dr. Andrew Pinto holds a Canadian Institutes of Health Research Applied Public Health Chair and is supported as a Clinician-Scientist in the Department of Family and Community Medicine, Temerty Faculty of Medicine, University of Toronto, and supported by the Department of Family and Community Medicine, St. Michael’s Hospital, and the Li Ka Shing Knowledge Institute, St. Michael’s Hospital. He is also the Associate Director for Clinical Research at the University of Toronto Practice-Based Research Network. Lawrence Paszat is supported by a Clinician Scientist award funded by the Ontario Ministry of Health and Long Term Care.Background The BETTER intervention is an effective comprehensive evidence-based program for chronic disease prevention and screening (CDPS) delivered by trained prevention practitioners (PPs), a new role in primary care. An adapted program, BETTER HEALTH, delivered by public health nurses as PPs for community residents in low income neighbourhoods, was recently shown to be effective in improving CDPS actions. To obtain a nuanced understanding about the CDPS needs of community residents and how the BETTER HEALTH intervention was perceived by residents, we studied how the intervention was adapted to a public health setting then conducted a post-visit qualitative evaluation by community residents through focus groups and interviews. Methods We first used the ADAPT-ITT model to adapt BETTER for a public health setting in Ontario, Canada. For the post-PP visit qualitative evaluation, we asked community residents who had received a PP visit, about steps they had taken to improve their physical and mental health and the BETTER HEALTH intervention. For both phases, we conducted focus groups and interviews; transcripts were analyzed using the constant comparative method. Results Thirty-eight community residents participated in either adaptation (n = 14, 64% female; average age 54 y) or evaluation (n = 24, 83% female; average age 60 y) phases. In both adaptation and evaluation, residents described significant challenges including poverty, social isolation, and daily stress, making chronic disease prevention a lower priority. Adaptation results indicated that residents valued learning about CDPS and would attend a confidential visit with a public health nurse who was viewed as trustworthy. Despite challenges, many recipients of BETTER HEALTH perceived they had achieved at least one personal CDPS goal post PP visit. Residents described key relational aspects of the visit including feeling valued, listened to and being understood by the PP. The PPs also provided practical suggestions to overcome barriers to meeting prevention goals. Conclusions Residents living in low income neighbourhoods faced daily stress that reduced their capacity to make preventive lifestyle changes. Key adapted features of BETTER HEALTH such as public health nurses as PPs were highly supported by residents. The intervention was perceived valuable for the community by providing access to disease prevention. Trial registration #NCT03052959, 10/02/2017.Peer reviewe

Count every newborn; a measurement improvement roadmap for coverage data.

BACKGROUND: The Every Newborn Action Plan (ENAP), launched in 2014, aims to end preventable newborn deaths and stillbirths, with national targets of ≤12 neonatal deaths per 1000 live births and ≤12 stillbirths per 1000 total births by 2030. This requires ambitious improvement of the data on care at birth and of small and sick newborns, particularly to track coverage, quality and equity. METHODS: In a multistage process, a matrix of 70 indicators were assessed by the Every Newborn steering group. Indicators were graded based on their availability and importance to ENAP, resulting in 10 core and 10 additional indicators. A consultation process was undertaken to assess the status of each ENAP core indicator definition, data availability and measurement feasibility. Coverage indicators for the specific ENAP treatment interventions were assigned task teams and given priority as they were identified as requiring the most technical work. Consultations were held throughout. RESULTS: ENAP published 10 core indicators plus 10 additional indicators. Three core impact indicators (neonatal mortality rate, maternal mortality ratio, stillbirth rate) are well defined, with future efforts needed to focus on improving data quantity and quality. Three core indicators on coverage of care for all mothers and newborns (intrapartum/skilled birth attendance, early postnatal care, essential newborn care) have defined contact points, but gaps exist in measuring content and quality of the interventions. Four core (antenatal corticosteroids, neonatal resuscitation, treatment of serious neonatal infections, kangaroo mother care) and one additional coverage indicator for newborns at risk or with complications (chlorhexidine cord cleansing) lack indicator definitions or data, especially for denominators (population in need). To address these gaps, feasible coverage indicator definitions are presented for validity testing. Measurable process indicators to help monitor health service readiness are also presented. A major measurement gap exists to monitor care of small and sick babies, yet signal functions could be tracked similarly to emergency obstetric care. CONCLUSIONS: The ENAP Measurement Improvement Roadmap (2015-2020) outlines tools to be developed (e.g., improved birth and death registration, audit, and minimum perinatal dataset) and actions to test, validate and institutionalise proposed coverage indicators. The roadmap presents a unique opportunity to strengthen routine health information systems, crosslinking these data with civil registration and vital statistics and population-based surveys. Real measurement change requires intentional transfer of leadership to countries with the greatest disease burden and will be achieved by working with centres of excellence and existing networks

Late Effects in Hematopoietic Cell Transplant Recipients with Acquired Severe Aplastic Anemia: A Report from the Late Effects Working Committee of the Center for International Blood and Marrow Transplant Research

With improvements in hematopoietic cell transplant (HCT) outcomes for severe aplastic anemia (SAA), there is a growing population of SAA survivors after HCT. However, there is a paucity of information regarding late effects that occur after HCT in SAA survivors. This study describes the malignant and nonmalignant late effects in survivors with SAA after HCT. A descriptive analysis was conducted of 1718 patients post-HCT for acquired SAA between 1995 and 2006 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). the prevalence and cumulative incidence estimates of late effects are reported for 1-year HCT survivors with SAA. of the HCT recipients, 1176 (68.5%) and 542 (31.5%) patients underwent a matched sibling donor (MSD) or unrelated donor (URD) HCT, respectively. the median age at the time of HCT was 20 years. the median interval from diagnosis to transplantation was 3 months for MSD HCT and 14 months for URD HCT. the median follow-up was 70 months and 67 months for MSD and URD HCT survivors, respectively. Overall survival at I year, 2 years, and 5 years for the entire cohort was 76% (95% confidence interval [CI]: 74-78), 73% (95% CI: 71-75), and 70% (95% CI: 68-72). Among 1-year survivors of MSD HCT, 6% had 1 late effect and 1% had multiple late effects. for 1-year survivors of URD HCT, 13% had 1 late effect and 2% had multiple late effects. Among survivors of MSD HCT, the cumulative incidence estimates of developing late effects were all <3% and did not increase over time. in contrast, for recipients of URD HCT, the cumulative incidence of developing several late effects exceeded 3% by 5 years: gonadal dysfunction 10.5% (95% CI: 7.3-14.3), growth disturbance 7.2% (95% CI: 4.4-10.7), avascular necrosis 6.3% (95% CI: 3.6-9.7), hypothyroidism 5.5% (95% CI: 2.8-9.0), and cataracts 5.1% (95% CI: 2.9-8.0). Our results indicated that all patients undergoing HCT for SAA remain at risk for late effects, must be counseled about, and should be monitored for late effects for the remainder of their lives.Public Health Service Grant from the National Cancer InstituteNational Heart, Lung, and Blood InstituteNational Institute of Allergy and Infectious DiseasesNational Cancer InstituteHealth Resources and Services Administration/Department of Health and Human ServicesOffice of Naval ResearchAllosAmgenAngioblastChildrens Hosp Orange Cty, Dept Hematol, Orange, CA 92668 USACIBMTR Med Coll Wisconsin, Dept Biostat, Milwaukee, WI USAMed Coll Wisconsin, CIBMTR Stat Ctr, Milwaukee, WI 53226 USAKing Faisal Specialist Hosp & Res Ctr, Dept Oncol, Riyadh 11211, Saudi ArabiaNew York Med Coll, Dept Pediat Hematol Oncol & Stem Cell Transplanta, Valhalla, NY 10595 USAStemcyte, Covina, CA USADana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USAUniv Florida, Dept Hematol Oncol, Gainesville, FL USAPrincess Margaret Hosp, Dept Med, Toronto, ON M4X 1K9, CanadaUniv S Florida, All Childrens Hosp, Dept Pediat Hematol & Oncol, St Petersburg, FL 33701 USAUniv Basel Hosp, Dept Hematol, CH-4031 Basel, SwitzerlandOregon Hlth & Sci Univ, Dept Hematol & Oncol, Portland, OR 97201 USAChildrens Natl Med Ctr, Dept Blood & Marrow Transplantat, Washington, DC 20010 USABaylor Coll Med, Ctr Cell Therapy, Dept Hematol & Oncol, Houston, TX 77030 USAUniv N Carolina Hosp, Dept Pediat, Chapel Hill, NC USAUniv Hosp Case, Med Ctr, Dept Med, Cleveland, OH USAUniv Arkansas Med Sci, Dept Hematol & Oncol, Little Rock, AR 72205 USACincinnati Childrens Hosp Med Ctr, Dept Bone Marrow Transplantat & Immune Deficiency, Cincinnati, OH USATufts Med Ctr, Dept Med & Pediat, Boston, MA USAUniv S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Hematol & Oncol, Tampa, FL 33612 USAFlorida Ctr Cellular Therapy, Dept Med, Orlando, FL USAUniv Fed Parana, Dept Bone Marrow Transplantat, BR-80060000 Curitiba, Parana, BrazilVanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USAInst Oncol Pediat, Dept Pediat, São Paulo, BrazilFred Hutchinson Canc Res Ctr, Dept Clin Res & Transplantat, Seattle, WA 98104 USAMt Sinai Med Ctr, Dept Bone Marrow & Stem Cell Transplantat, New York, NY 10029 USAUniv N Carolina Hosp, Dept Hematol & Oncol, Chapel Hill, NC USAUniv Manitoba, CancerCare Manitoba, Dept Manitoba Blood & Marrow Transplant Program, Winnipeg, MB, CanadaKarolinska Univ Hosp, Ctr Allogene Stem Cell Transplantat, Dept Pediat, Stockholm, SwedenLouisiana State Univ, Hlth Sci Ctr, Childrens Hosp, Dept Pediat, New Orleans, LA USADept Natl Marrow Donor Program, Minneapolis, MN USAPublic Health Service Grant from the National Cancer Institute: U24-CA76518National Heart, Lung, and Blood Institute: 5U01HL069294Office of Naval Research: N00014-06-1-0704Office of Naval Research: N00014-08-1-0058HHSH234200637015CWeb of Scienc