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•Fifty-five patients with bronchiolitis obliterans syndrome (BOS) were followed for infectious complications and changes in lung function.•More than one-half of the patients developed at least 1 lower respiratory tract infection (LRTI); infections were often recurrent.•Viral LRTIs predominated, followed by bacterial LRTIs (especially due to Pseudomonas aeruginosa). Nontuberculous mycobacteria (NTM) were unexpectedly common.•BOS patients with LRTIs had inferior lung function compared to those without and trended toward decreased overall survival.•Patients with BOS should be monitored closely for LRTIs, including those due to NTM.

Monitoring of measurable residual disease (MRD) is essential to the management of acute lymphoblastic leukemia (ALL) and is typically performed through repeated bone marrow (BM) assessments. Using a next-generation sequencing (NGS) MRD platform, we performed a prospective observational study evaluating the correlation between peripheral blood (PB) and BM MRD in adults with ALL receiving cellular therapies (hematopoietic cell transplantation [HCT] and chimeric antigen receptor T-cell [CAR-T] therapies). Among the study cohort (N = 69 patients; 126 paired PB/BM samples), we found strong correlation between PB and BM MRD (r = 0.87; P < .001), with a sensitivity and specificity of MRD detection in the PB of 87% and 90%, respectively, relative to MRD in the BM. MRD became detectable in the PB in 100% of patients who subsequently relapsed following HCT, with median time from MRD+ to clinical relapse of 90 days, and in 85% of patients who relapsed following CAR T, with median time from MRD+ to clinical relapse of 60 days. In adult patients with ALL undergoing cellular therapies, we demonstrate strong concordance between NGS-based MRD detected in the PB and BM. Monitoring of ALL MRD in the PB appears to be an adequate alternative to frequent invasive BM evaluations in this clinical setting.

Monitoring of measurable residual disease (MRD) is essential to the management of acute lymphoblastic leukemia (ALL) and is typically performed through repeated bone marrow (BM) assessments. Using a next-generation sequencing (NGS) MRD platform, we performed a prospective observational study evaluating the correlation between peripheral blood (PB) and BM MRD in adults with ALL receiving cellular therapies (hematopoietic cell transplantation [HCT] and chimeric antigen receptor T-cell [CAR-T] therapies). Among the study cohort (N = 69 patients; 126 paired PB/BM samples), we found strong correlation between PB and BM MRD (r= 0.87; P< .001), with a sensitivity and specificity of MRD detection in the PB of 87% and 90%, respectively, relative to MRD in the BM. MRD became detectable in the PB in 100% of patients who subsequently relapsed following HCT, with median time from MRD+to clinical relapse of 90 days, and in 85% of patients who relapsed following CAR T, with median time from MRD+to clinical relapse of 60 days. In adult patients with ALL undergoing cellular therapies, we demonstrate strong concordance between NGS-based MRD detected in the PB and BM. Monitoring of ALL MRD in the PB appears to be an adequate alternative to frequent invasive BM evaluations in this clinical setting.

•Our study represents one of the only published randomized controlled trials on an advance care planning (ACP) intervention for patients undergoing allogeneic hematopoietic cell transplantation.•Patients were randomized to the traditional state advanced directive (AD) and a novel Stanford Letter AD.•Both groups in the study had a high AD completion rate, much higher than that reported historically elsewhere and at our own institution.•Incorporating ACP education and reminders throughout the transplantation process can increase AD completion rates.

Background: Protease-activated receptor-1 antagonism by vorapaxar could facilitate arteriovenous fistula maturation but may increase bleeding risk.Objective: The primary objective of the Vorapaxar Study for Maturation of arteriovenous fistula for Hemodialysis Access (VorapAccess) was to determine if vorapaxar improves arteriovenous fistula functional maturation in patients with end-stage renal disease.Methods: VorapAccess was a randomized, placebo-controlled, double-blind pilot trial comparing 2.5 mg vorapaxar per day with placebo for twelve weeks starting on day two after arteriovenous fistula creation. The primary outcome was time to functional maturation defined as successful cannulation for six hemodialysis sessions within three weeks. The planned sample size was 50 participants. The study was terminated early after withdrawal of planned financial support. Given the small number of randomized patients, we performed descriptive analyses without inference testing.Results: A total of 13 participants were randomly allocated study drug (six vorapaxar and seven placebo). The median age was 56 years and seven participants (54%) were female. The median (minimum–maximum) days to functional maturation were 169 (77–287) days in the vorapaxar group and 145 (48–198) days in the placebo group. Six of the 13 (46%) participants had arteriovenous fistula functional maturation within 180 days; two of six (33%) in the vorapaxar group and four of seven (57%) in the placebo group. There was one bleeding event in the placebo group.Conclusion: Fewer than half of participants had functional maturation within 180 days after surgery, suggesting a major need for agents or strategies that enhance arteriovenous fistula maturation.

History of postembolization syndrome, tumor burden, and drug-eluting embolic chemoembolization were related to protracted recovery because of postembolization syndrome following chemoembolization for hepatocellular carcinoma.

IMPORTANCE: Although lay health workers (LHWs) improve cancer screening and treatment adherence, evidence on whether they can enhance other aspects of care is limited. OBJECTIVE: To determine whether an LHW program can increase documentation of patients’ care preferences after cancer diagnosis. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted from August 13, 2013, through February 2, 2015, among 213 patients with stage 3 or 4 or recurrent cancer at the Veterans Affairs Palo Alto Health Care System. Data analysis was by intention to treat and performed from January 15 to August 18, 2017. INTERVENTIONS: Six-month program with an LHW trained to assist patients with establishing end-of-life care preferences vs usual care. MAIN OUTCOMES AND MEASURES: The primary outcome was documentation of goals of care. Secondary outcomes were patient satisfaction on the Consumer Assessment of Health Care Providers and Systems “satisfaction with provider” item (on a scale of 0 [worst] to 10 [best possible]), health care use, and costs. RESULTS: Among the 213 participants randomized and included in the intention-to-treat analysis, the mean (SD) age was 69.3 (9.1) years, 211 (99.1%) were male, and 165 (77.5%) were of non-Hispanic white race/ethnicity. Within 6 months of enrollment, patients randomized to the intervention had greater documentation of goals of care than the control group (97 [92.4%] vs 19 [17.5%.]; P &lt; .001) and larger increases in satisfaction with care on the Consumer Assessment of Health Care Providers and Systems “satisfaction with provider” item (difference-in-difference, 1.53; 95% CI, 0.67-2.41; P &lt; .001). The number of patients who died within 15 months of enrollment did not differ between groups (intervention, 60 of 105 [57.1%] vs control, 60 of 108 [55.6%]; P = .68). In the 30 days before death, patients in the intervention group had greater hospice use (46 [76.7%] vs 29 [48.3%]; P = .002), fewer emergency department visits (mean [SD], 0.05 [0.22] vs 0.60 [0.76]; P &lt; .001), fewer hospitalizations (mean [SD], 0.05 [0.22] vs 0.50 [0.62]; P &lt; .001), and lower costs (median [interquartile range], $1048 [$331-$8522] vs $23 482 [$9708-$55 648]; P &lt; .001) than patients in the control group. CONCLUSIONS AND RELEVANCE: Incorporating an LHW into cancer care increases goals-of-care documentation and patient satisfaction and reduces health care use and costs at the end of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02966509

Preterm/very low birth weight infants may suffer neurodevelopmental delays. Pediatricians should monitor neurodevelopment and pursue timely referrals. Yet parents who speak non-English primary languages (NEPL) report worse health care communication and fewer appropriate specialty referrals for their children. We sought to determine whether infants of NEPL parents receive recommended outpatient follow-up care for neurodevelopment. We hypothesized that these infants received less care than infants of English speakers.

Positron emission tomography (PET) is a diagnostic tool for lung cancer evaluation. No studies have ascertained practice patterns and determined the appropriateness of PET imaging in a large group of US patients with screen-detected lung nodules.

Frontline providers frequently make time-sensitive antibiotic choices, but many feel poorly equipped to handle antibiotic allergies.

OBJECTIVE To evaluate the evidence that quality improvement (QI) strategies can improve the processes and outcomes of outpatient pediatric asthma care. DATA SOURCES Cochrane Effective Practice and Organisation of Care Group database (January 1966 to April 2006), MEDLINE (January 1966 to April 2006), Cochrane Consumers and Communication Group database (January 1966 to May 2006), and bibliographies of retrieved articles. STUDY SELECTION Randomized controlled trials, controlled before-after trials, or interrupted time series trials of English-language QI evaluations. INTERVENTIONS Must have included 1 or more QI strategies for the outpatient management of children with asthma. MAIN OUTCOME MEASURES Clinical status (eg, spirometric measures); functional status (eg, days lost from school); and health services use (eg, hospital admissions). RESULTS Seventy-nine studies met inclusion criteria: 69 included at least some component of patient education, self-monitoring, or self-management; 13 included some component of organizational change; and 7 included provider education. Self-management interventions increased symptom-free days by approximately 10 days/y (P = .02) and reduced school absenteeism by about 0.1 day/mo (P = .03). Interventions of provider education and those that incorporated organizational changes were likely to report improvements in medication use. Quality improvement interventions that provided multiple educational sessions, had longer durations, and used combinations of instructional modalities were more likely to result in improvements for patients than interventions lacking these characteristics. CONCLUSIONS A variety of QI interventions improve the outcomes and processes of care for children with asthma. Use of similar outcome measures and thorough descriptions of interventions would advance the study of QI for pediatric asthma care.Arch Pediatr Adolesc Med. 2009;163(6):572-581--

Muffly: Adaptive: Research Funding; Amgen: Consultancy; Servier: Research Funding. Meyer:Orca Bio: Research Funding. Negrin:Amgen: Consultancy; Magenta Therapeutics: Consultancy, Current equity holder in publicly-traded company; BioEclipse Therapeutics: Current equity holder in private company; Biosource: Current equity holder in private company; UpToDate: Honoraria; KUUR Therapeutics: Consultancy. Rezvani:Pharmacyclics: Research Funding. Sidana:Janssen: Consultancy. Shiraz:ORCA BioSystems: Research Funding; Kite, a Gilead Company: Research Funding. Shizuru:Jasper Therapeutics, Inc: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Liedtke:Adaptive: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria. Miklos:Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Adaptive Biotech: Consultancy, Other: Travel support, Research Funding; Allogene Therapeutics Inc.: Research Funding; Novartis: Consultancy, Other: Travel support, Research Funding; Pharmacyclics: Consultancy, Other: Travel support, Patents & Royalties, Research Funding; Juno-Celgene-Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Janssen: Consultancy, Other: Travel support; Miltenyi Biotec: Research Funding.

Background:

Care remains suboptimal for many patients with hypertension.

The Pan-Canadian Early Detection of Lung Cancer (PanCan) risk model and the Lung CT Screening Reporting & Data System (Lung-RADS) estimate cancer probability for screening-detected nodules. The accuracy and agreement of these models require further study.

Muffly: Adaptive Biotechnologies: Research Funding; Shire Pharmaceuticals: Research Funding.

Lynch: Johnson Graffe Keay Moniz & Wick LLP: Consultancy; Rhizen Pharmaceuticals S.A.: Research Funding; Takeda Pharmaceuticals: Research Funding; T.G. Therapeutics: Research Funding; Incyte Corporation: Research Funding. Advani:Agensys: Other: Institutional Research Support; Celgene: Other: Institutional Research Support; Regeneron Pharmaceuticals, Inc.: Other: Institutional Research Support; Bayer Healthcare Pharmaceuticals: Other: Consultancy/Advisory Role; Bristol Myers Squibb: Other: Consultancy/Advisory role and Institutional Research Support; Millenium: Other: Institutional Research Support; Kura: Other: Institutional Research Support; Infinity: Other: Institutional Research Support; Kyowa: Other: Consulting/Advisory Role; Merck: Other: Institutional Research Support; Gilead/Kite: Other: Consultancy/Advisory Role; Forty Seven, Inc: Other: Institutional Research Support; Janssen Pharmaceutical: Other: Institutional Research Support; AstraZeneca: Other: Consultancy/Advisory Role; Roche/Genentech: Other: Consultancy/Advisory Role, Institutional Research Support; Takeda: Other: Consultancy/Advisory Role; Cell Medica: Other: Consultancy/Advisory Role; Autolus: Other: Consultancy/Advisory Role; Seattle Genetics: Other: Consultancy/Advisory role, Institutional Research Support; Pharmacyclics: Other: Institutional Research Support.

Background: Classic Hodgkin lymphoma (CHL) is currently highly curable. Surveillance guidelines have been extrapolated largely from an era where sophisticated staging techniques were lacking, radiotherapy alone was the mainstay of therapy, and cure rates were lower. While the lack of a role for surveillance imaging for patients (pts) in complete remission (CR) at end of therapy (EOT) is well established, there is paucity of data regarding role of laboratory testing. Current NCCN guidelines recommend complete blood counts (CBC), chemistry panels, and erythrocyte sedimentation rate (ESR) “as clinically indicated,” while ESMO recommends testing be performed at each clinic visit. To assess the utility of surveillance laboratory testing in detecting relapse, we conducted a retrospective analysis.

Background

Recombinant factor VIIa (rFVIIa) is a potent hemostatic agent licensed for treatment of bleeding in hemophiliac patients with inhibitors but has been increasingly used off-label to treat or prevent bleeding, despite sparse data to support its efficacy and a possible increase in thromboembolic events. While randomized controlled trials (RCTs) provide the best evidence regarding efficacy, they may not identify rare but important adverse events. Observational studies may capture the rate of such events in clinical practice more accurately.To compare rates of thromboembolic events associated with off-label use of rFVIIa in RCTs and observational studies.Studies of off-label application of rFVIIa were identified by review of 10 literature and clinical trial databases through February, 2009. The off-label indications examined were trauma, non-traumatic intracranial hemorrhage (ICH), and adult cardiac surgery. When an appropriate number and quality of studies were available, data from RCTs and higher quality comparative observational studies were combined via meta-analysis using the arc sine statistical method, a method that characterizes uncommon events more accurately than more conventional methods. To describe the absolute rate of thromboembolism for patients treated with rFVIIa in RCTs versus observational studies, we analyzed data from the interventional arms of RCTs and comparative observational studies, as well as data from non-comparative observational studies with 15 or more patients.Included Studies Our search identified 4 RCTs and 4 observational studies of rFVIIa use in ICH. Two RCTs and 5 observational studies were identified for trauma. For cardiac surgery, 2 RCTs, 2 higher quality comparative observational studies (included in the meta-analysis), and 8 additional observational studies were identified. Meta-analyses The meta-analysis of the RCTs investigating use of rFVIIa in ICH showed a trend toward increased thromboembolic risk with rFVIIa (arcsine summary effect size 0.100, 95% CI -0.072-0.272). For trauma, the two RCTs did not provide sufficient data to perform meta-analysis. Individually, they did not demonstrate significantly different incidences of thromboembolic events with rFVIIa compared to placebo but may have been underpowered to detect such differences. For cardiac surgery, the meta-analysis of the 4 studies showed a significant increase in thromboembolic events in the rFVIIa group (arcsine summary effect 0.14; 95% CI 0.038- 0.242). Absolute rates of thromboembolic events in RCTs versus observational studies In ICH, thromboembolic event rates in the treatment arms of the RCTs ranged from 0.07-0.11, while those in the observational studies ranged from 0-0.20. In trauma, thromboembolic event rates in the RCT treatment arms ranged from 0.03-0.06, whereas those in the observational studies ranged from 0.02-0.11. In cardiac surgery, thromboembolic event rates in the RCTs ranged from 0.07-0.22 compared to a range of 0-0.25 in the observational studies. For all three indications, Figure 1 shows that the weighted mean thromboembolic event rates associated with rFVIIa use are higher in the observational studies than in the RCTs. Patients in the observational studies tended to be older and have a worse prognosis than those enrolled in the RCTs.We identified a trend toward significantly higher rates of thromboembolic adverse events with off-label use of rFVIIa compared to placebo in our meta-analyses of ICH and cardiac surgery, but no similar pattern in trauma trials. For each of these indications, we identified a higher rate of thromboembolic adverse events associated with the use of rFVIIa in observational trials compared to RCTs. This finding suggests that patients receiving off-label rFVIIa for these off-label indications in real-world practice may be at higher risk of thromboembolic events than patients enrolled in clinical trials and may caution against widespread use, especially in the absence of convincing data on efficacy.Off Label Use: This study examines the off-label use of rFVIIa in randomized controlled trials and observational studies of intracranial hemorrhage, trauma, and cardiac surgery.

Abstract 1403