Citations

AbstractVenous thromboembolic (VTE) complications in children and adolescents with acute lymphoblastic leukaemia (ALL) and T or B cell lymphoblastic lymphoma (T/B cell LL) can result not only in life-threatening acute complications but also contribute to significant long-term sequelae. The PREVAPIX-ALL study is an open-label randomized controlled study comparing outcomes of treatment with prophylactic dose apixaban versus no anticoagulation (standard of care) in children and adolescents with ALL and T/B cell LL receiving standard induction chemotherapy with asparaginase and the presence of a central venous access device. On day 29 of induction, all patients undergo screening imaging with duplex ultrasonography and echocardiography. The primary efficacy endpoint of the study is a composite of symptomatic and asymptomatic VTE that includes deep vein thrombosis, pulmonary embolism, cerebral sinovenous thrombosis or VTE-related death. The primary safety outcome is major bleeding. Secondary outcomes are central line-associated infections, patency and line replacement, superficial thrombosis, arterial events and death. A planned sample size of 500 randomized paediatric patients enrolled over a period of 5 years is based on the estimation of VTE rates of 20 and 10% in the standard of care and apixaban groups, respectively. An optional biomarker study in 150 patients will examine predictors of increased VTE risk and study in vivo anticoagulant effects of apixaban in children by measuring specific biomarkers in the haemostatic system and inflammatory pathway. This study will provide valuable information for the safety and efficacy of apixaban in VTE prevention during induction in paediatric ALL.

ABSTRACTIntroductionOnion‐bulbs (OB) are concentrically layered Schwann‐cell processes, surrounding nerve fibers, occurring in both inherited and acquired demyelinating polyneuropathies. We investigated whether OB patterns (generalized, mixed, or focal) correlate with acquired or inherited neuropathies.MethodsOne hundred thirty‐one OB‐rich nerve biopsies were graded for OB pattern and inflammation without knowledge of clinical history. We classified inherited (n = 49) or acquired (n = 82) neuropathies based solely on clinical history.ResultsFifty‐one biopsies had generalized (34 inherited vs. 17 acquired, P < 0.001), 54 mixed (48 acquired vs. 6 inherited, P < 0.001), and 26 focal/multifocal (inherited [n = 9], acquired [n = 17]) OB. Inflammation occurred more frequently in acquired (n = 54) than inherited (n = 14) neuropathy (P = 0.004).DiscussionGeneralized OB correlates with inherited neuropathy; mixed OB with acquired. Inflammation occurs more in acquired neuropathy cases. OB patterns are best explained by ubiquitous Schwann‐cell involvement in inherited and multifocal Schwann‐cell involvement in acquired neuropathies and predict the electrophysiology of uniform demyelination in inherited and unequal demyelination in acquired neuropathies. Muscle Nerve 59:665–670, 2019

ABSTRACTObjectives:The aim of the present study was to investigate the natural history of chronic pancreatitis (CP); patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared.Methods:Demographics, risk factors, disease duration, management and outcomes of 224 children and 1063 adults were compared using appropriate statistical tests for categorical and continuous variables.Results:Alcohol was a risk in 53% of adults and 1% of children (P < 0.0001); tobacco in 50% of adults and 7% of children (P < 0.0001). Obstructive factors were more common in children (29% vs 19% in adults, P = 0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, P = 0.107). Diabetes was more common in adults than children (36% vs 4% respectively, P < 0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2‐CO) were compared with INSPPIRE subjects. These 2 cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2‐CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2‐CO vs 1% INSPPIRE cohorts, P = 0.011).Conclusions:Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.

The objective was to quantitatively evaluate clinician characteristics associated with unwarranted practice variation, and how clinical care algorithms influence this variation. Participants (142 physicians, 53 nurse practitioners, and 9 physician assistants in family medicine, internal medicine, and cardiology) described their management of 4 clinical vignettes, first based on their own practice (unguided), then using care algorithms (guided). The authors quantitatively estimated variation in management. Cardiologists demonstrated 17% lower variation in unguided responses than generalists (fold-change 0.83 [95% confidence interval (CI) 0.68, 0.97]), and those who agreed that practice variation can realistically be reduced had 16% lower variation than those who did not (fold-change 0.84 [CI, 0.71, 0.99]). A 17% reduction in variation was observed for guided responses compared with baseline (unguided) responses (fold-change 0.83 [CI, 0.76, 0.90]). Differences were otherwise similar across clinician subgroups and attitudes. Unwarranted practice variation was similar across most clinician subgroups. The authors conclude that care algorithms can reduce variation in management.

656 Background: Despite multiple trials of new agents in metastatic colorectal cancer (mCRC), long term outcomes remain poor. This study explores the changing trends in the design, interpretation and outcomes of phase III randomized controlled trials (RCT) in mCRC over time. Methods: Phase III RCTs of systemic therapy for mCRC with enrollment between 1986 and 2016 were identified through 4 electronic databases and grouped into 3 time periods (1986-1996 – T1; 1997-2006 – T2 & 2007-2016 – T3). Study selection, quality appraisal and data collection were performed by 2 independent investigators. Study characteristics, primary and secondary endpoints, and authors’ interpretation of results and conclusions were analyzed. Improvement in overall survival (OS) was the difference between experimental and control arms. A study was deemed positive if it met its end point, was recommended for further study or for adoption for clinical use (p ≤ 0.05 significant for all analyses). Results: One hundred fifty trials (T1=36, T2=62, T3=52) with 77494 patients (T1=12406, T2=39158, T3=25930) were included. Although 1st line therapy trials continued to be the most common across all T, the percentage (%) of trials evaluating 3rd line and beyond (T1=0, T2=3, T3=27) have increased significantly over time as have trials with targeted agents (T1=11, T2=34, T3=79). Although OS remains the most common primary end point, more trials in T2 & T3 have used progression-free survival instead (14 vs 47 & 44). The % of trials with negative results but interpreted as positive increased over time (T1=18; T2=42; T3=35). Across all T, the median improvement in OS (months, m) of these trials was significantly lower compared to the trials that met primary end point across all T (T1 = 0 vs 1.8 m, T2 = -0.1 vs 3.25, T3 = -0.25 vs 2.55). Conclusions: A significant shift has occurred over the past three decades in the design and interpretation of phase III trials in advanced CRC. Any interpretations of potential survival benefits from trials that have not met primary end point must be made with significant caution.

Little is known about whether adolescent participation in sexual health research prompts adolescents and parents to have conversations about sensitive topics. One year after being presented with a hypothetical microbicide safety study, 248 adolescent–parent dyads were asked about conversations they may have had after their initial study visit. Sixty-three per cent of adolescents and 82% of parents reported having a conversation about the study. A launching conversation about broader topics (e.g. risk behaviours) was reported by 8% of adolescents and 17% of parents. Because there is evidence that conversations are occurring, researchers could provide guidance to help facilitate potentially sensitive discussions.

ABSTRACT Background and purpose: The use of pulmonary ultrasound (US) in the critical care setting has been increasing over the past 2 decades. The use of advanced practice providers (APPs) in the critical care setting is also increasing. Limited data exist regarding the clinical and educational impact of a formal pulmonary US training course for APPs working in critical care settings. Methods: A preimplementation and postimplementation comparative design focused on the development and implementation of a formal pulmonary US course for novice critical care APPs. Conclusions: Eleven APPs underwent formal pulmonary US training. There was a significant increase in pulmonary US knowledge after the course, with pretest median of 13 and posttest median of 22 (p < .001; maximum score = 23). Presurvey and postsurvey comparison showed overall increase in skill and clinical use of pulmonary US. After the course, participating APPs reported a greater frequency of clinical decision-making based on US examination as measured by presurvey and postsurvey results. Implications for practice: Implementation of a formal pulmonary US course for critical care APPs improved pulmonary US knowledge, skill, and utilization, and impacted clinical decision-making and should be a highly recommended addition to the practice setting.