ATS-NHLBI Asthma COPD Overlap (ACO) Workshop Report.

Am J Respir Crit Care Med. 2017 Jun 21;:

Authors: Woodruff PG, van den Berge M, Boucher RC, Brightling C, Burchard EG, Christenson SA, Han MK, Holtzman MJ, Kraft M, Lynch DA, Martinez FD, Reddel HK, Sin DD, Washko GR, Wenzel SE, Punturieri A, Freemer MM, Wise RA

Abstract
Asthma and COPD are highly prevalent chronic obstructive lung diseases with an associated high burden of disease. Asthma, which is often allergic in origin, frequently begins in infancy or childhood with variable airflow obstruction and intermittent wheezing, cough, and dyspnea. Patients with COPD, in contrast, are usually current or former smokers who present after the age of 40 years with symptoms (often persistent), including dyspnea and a productive cough. Based on age and smoking history, it is often easy to distinguish between asthma and COPD. However, some patients have features compatible with both diseases. Because clinical studies typically exclude these patients, their underlying disease mechanisms and appropriate treatment remain largely uncertain. To explore the status of and opportunities for research in this area, the National Heart, Lung, and Blood Institute (NHLBI) in partnership with the American Thoracic Society (ATS) convened a workshop of investigators in San Francisco (CA) on May 14, 2016. At the workshop, current understanding of Asthma-COPD overlap was discussed among clinicians, pathologists, radiologists, epidemiologists, and investigators with expertise in asthma and COPD. They considered knowledge gaps in our understanding of Asthma-COPD overlap and identified strategies and research priorities that will advance its understanding. This report summarizes those discussions.

PMID: 28636425 [PubMed - as supplied by publisher]

On the importance of accurate quantification of individual volatile metabolites in exhaled breath.

J Breath Res. 2017 Jun 21;:

Authors: Smith D, Spanel P

Abstract
It is argued that shortcomings of certain approaches to breath analysis research based on superficial interpretation of non-quantitative data are inadvertently inhibiting the progression of non-invasive breath analysis into clinical practice. The objective of this perspective is to suggest more clinically profitable approaches to breath research. Thus, following a discourse on the challenges and expectations in breath research, a brief indication is given of the analytical techniques currently used for the analysis of very humid exhaled breath. The seminal work that has been carried out using GC-MS revealed that exhaled breath comprises large numbers of trace volatile organic compounds, VOCs. Unfortunately, analysis of these valuable GC-MS data is mostly performed using chemometrics to distinguish the VOC content of breath samples collected from patients and healthy controls, and reliable quantification of the VOCs is rarely deemed necessary. This limited approach ignores the requirements of clinically acceptable biomarkers and misses the opportunity to identify relationships between the concentrations of individual VOCs and certain related physiological or metabolic parameters. Therefore, a plea is made for more effort to be directed towards the positive identification and accurate quantification of individual VOCs in exhaled breath, which are more physiologically meaningful as best exemplified by the quantification of breath nitric oxide, NO. Support for the value of individual VOC quantification is illustrated by the SIFT-MS studies of breath hydrogen cyanide, HCN, a biomarker of Pseudomonas aeruginosa infection, breath acetic acid as an indicator of airways acidification in cystic fibrosis patients, and n-pentane as a breath biomarker of inflammation in idiopathic bowel disease patients. These single VOCs could be used as non-invasive monitors of the efficacy of therapeutic intervention. The increase of breath methanol following the ingestion of a known amount of the sweetener aspartame impressively shows that accurate breath analysis is a reliable indicator of blood.

PMID: 28635619 [PubMed - as supplied by publisher]

Heparin: new life for an old drug.

Nanomedicine (Lond). 2017 Jun 21;:

Authors: Aláez-Versón CR, Lantero E, Fernàndez-Busquets X

Abstract
Heparin is one of the oldest drugs, which nevertheless remains in widespread clinical use as an inhibitor of blood coagulation. The history of its identification a century ago unfolded amid one of the most fascinating scientific controversies turning around the distribution of credit for its discovery. The composition, purification and structure-function relationship of this naturally occurring glycosaminoglycan regarding its classical role as anticoagulant will be dealt with before proceeding to discuss its therapeutic potential in, among other, inflammatory and infectious disease, cancer treatment, cystic fibrosis and Alzheimer's disease. The first bibliographic reference hit using the words 'nanomedicine' and 'heparin' is as recent as 2008. Since then, nanomedical applications of heparin have experienced an exponential growth that will be discussed in detail, with particular emphasis on its antimalarial activity. Some of the most intriguing potential applications of heparin nanomedicines will be exposed, such as those contemplating the delivery of drugs to the mosquito stages of malaria parasites.

PMID: 28635544 [PubMed - as supplied by publisher]

Psl Produced by Mucoid Pseudomonas aeruginosa Contributes to the Establishment of Biofilms and Immune Evasion.

MBio. 2017 Jun 20;8(3):

Authors: Jones CJ, Wozniak DJ

Abstract
Despite years of research and clinical advances, chronic pulmonary infections with mucoid Pseudomonas aeruginosa remain the primary concern for cystic fibrosis patients. Much of the research on these strains has focused on the contributions of the polysaccharide alginate; however, it is becoming evident that the neutral polysaccharide Psl also contributes to biofilm formation and the maintenance of chronic infections. Here, we demonstrate that Psl produced by mucoid strains has significant roles in biofilm structure and evasion of immune effectors. Though mucoid strains produce less Psl than nonmucoid strains, the Psl that is produced is functional, since it mediates adhesion to human airway cells and epithelial cell death. Additionally, Psl protects mucoid bacteria from opsonization and killing by complement components in human serum. Psl production by mucoid strains stimulates a proinflammatory response in the murine lung, leading to reduced colonization. To determine the relevance of these data to clinical infections, we tested Psl production and biofilm formation of a panel of mucoid clinical isolates. We demonstrated three classes of mucoid isolates, those that produce Psl and form robust biofilms, those that did not produce Psl and have a poor biofilm phenotype, and exopolysaccharide (EPS) redundant strains. Collectively, these experimental results demonstrate that Psl contributes to the biofilm formation and immune evasion of many mucoid strains. This is a novel role for Psl in the establishment and maintenance of chronic pulmonary infections by mucoid strains.IMPORTANCE Cystic fibrosis patients are engaged in an ongoing battle against chronic lung infections by the bacterium Pseudomonas aeruginosa One key factor contributing to the maintenance of chronic infections is the conversion to a mucoid phenotype, where the bacteria produce copious amounts of the polysaccharide alginate. Once the bacteria become mucoid, existing treatments are poorly effective. We proposed that mucoid bacteria produce an additional polysaccharide, Psl, which is important for their establishment and maintenance of chronic infections. This work demonstrates that Psl enhances attachment of mucoid bacteria to lung surfaces and leads to inflammation and damage in the lung. Additionally, we find that 50% of mucoid bacteria isolated from patients with chronic infections rely on Psl for the structure of their biofilm communities, suggesting that treatments against Psl should be investigated to enhance the success of current therapies.

PMID: 28634241 [PubMed - in process]

A Comparison of 2 Respiratory Devices for Sputum Clearance in Adults With Non-Cystic Fibrosis Bronchiectasis.

Respir Care. 2017 Jun 20;:

Authors: Silva YR, Greer TA, Morgan LC, Li F, Farah CS

Abstract
BACKGROUND: Airway clearance techniques are a vital part of routine care for patients with bronchiectasis. There is no clear superior modality. The Flutter combines oscillations (6-20Hz) and positive expiratory pressure; the Lung Flute combines positive expiratory pressure and low frequency acoustic waves (18-22Hz), to augment clearance. This project aimed to compare these devices.
METHODS: This was a randomized crossover study of adult subjects with stable non-cystic fibrosis bronchiectasis (expectorating >25 mL/d). Subjects attended 2 separate out-patient visits, 1 week apart, and completed a supervised sputum clearance regime and Lickert scale (8 questions regarding subjects' perception of the experience using each device). Total sputum expectorated during supervised intervention (T1) and after 30 min from the end of T1 (T2) was recorded as wet sputum weight. Total wet sputum weight desiccated in a microwave (10 min at 300 watts), allowed measurement of total dry sputum weight. Data were compared using paired t test.
RESULTS: We recruited 40 subjects with a mean ± SD age of 63 ± 16y. Overall, there was no significant difference in wet sputum weight (Flutter, 5.78 ± 6.47 g; Lung Flute, 5.75 ± 0.22g) and dry sputum weight (Flutter, 0.40 ± 0.86g; Lung Flute, 0.22 ± 0.21g). At T1, wet sputum weight was higher for the Flutter (5.10 ± 6.26g) compared with the Lung Flute (3.74 ± 3.44g) (P = .038). At T2, wet sputum weight was higher for the Lung Flute (2.02 ± 3.01g) compared with the Flutter (0.68 ± 0.75g) (P = .001). Subjects perceived the Flutter as being significantly better at clearing secretions (P = .01), easy to understand (P = .03), and simple to use (P = .01) compared with the Lung Flute.
CONCLUSIONS: Both devices were well-tolerated and successfully augmented secretion clearance. Most subjects preferred the Flutter because of increased speed of secretion clearance, and greater ease of use.

PMID: 28634173 [PubMed - as supplied by publisher]

Population Pharmacokinetics of Tobramycin Inhalation Solution in Pediatric Patients with Cystic Fibrosis.

J Pharm Sci. 2017 Jun 17;:

Authors: Wang X, Koehne-Voss S, Anumolu SS, Yu J

Abstract
Tobramycin inhalation solution (TOBI) given as a twice-daily inhalation of nebulized aerosols of 300 mg is approved for the treatment of Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients over 6 years of age. To investigate tobramycin pharmacokinetics (PK) after inhalation of TOBI in pediatric CF patients below 7 years, a population PK approach was used to evaluate tobramycin PK data in patients 6 months to 44 years of age from four clinical studies. The final model used a two-compartmental, first-order absorption model with effect of body mass index on the apparent central volume of distribution. Relative bioavailability in patients between 6 months and 7 years increased with age by a linear relationship, and was modeled as a ratio to that of patients over 7 years. Simulation showed steady-state concentrations of tobramycin are lower in pediatric patients 6 months to 6 years than those in patients over 6 years. However, systemic exposure is not predictive of clinical efficacy due to direct dosing at the infection site. Pseudomonas aeruginosa eradication rate and safety profile in patients less than 7 years of age were similar to patients older than 6 years, therefore no dose adjustment is warranted in the younger pediatric patients.

PMID: 28634121 [PubMed - as supplied by publisher]

Identification of intestinal ion transport defects in microvillus inclusion disease.

Am J Physiol Gastrointest Liver Physiol. 2016 Jul 01;311(1):G142-55

Authors: Kravtsov DV, Ahsan MK, Kumari V, van Ijzendoorn SC, Reyes-Mugica M, Kumar A, Gujral T, Dudeja PK, Ameen NA

Abstract
Loss of function mutations in the actin motor myosin Vb (Myo5b) lead to microvillus inclusion disease (MVID) and death in newborns and children. MVID results in secretory diarrhea, brush border (BB) defects, villus atrophy, and microvillus inclusions (MVIs) in enterocytes. How loss of Myo5b results in increased stool loss of chloride (Cl(-)) and sodium (Na(+)) is unknown. The present study used Myo5b loss-of-function human MVID intestine, polarized intestinal cell models of secretory crypt (T84) and villus resembling (CaCo2BBe, C2BBe) enterocytes lacking Myo5b in conjunction with immunofluorescence confocal stimulated emission depletion (gSTED) imaging, immunohistochemical staining, transmission electron microscopy, shRNA silencing, immunoblots, and electrophysiological approaches to examine the distribution, expression, and function of the major BB ion transporters NHE3 (Na(+)), CFTR (Cl(-)), and SLC26A3 (DRA) (Cl(-)/HCO3 (-)) that control intestinal fluid transport. We hypothesized that enterocyte maturation defects lead villus atrophy with immature secretory cryptlike enterocytes in the MVID epithelium. We investigated the role of Myo5b in enterocyte maturation. NHE3 and DRA localization and function were markedly reduced on the BB membrane of human MVID enterocytes and Myo5bKD C2BBe cells, while CFTR localization was preserved. Forskolin-stimulated CFTR ion transport in Myo5bKD T84 cells resembled that of control. Loss of Myo5b led to YAP1 nuclear retention, retarded enterocyte maturation, and a cryptlike phenotype. We conclude that preservation of functional CFTR in immature enterocytes, reduced functional expression of NHE3, and DRA contribute to Cl(-) and Na(+) stool loss in MVID diarrhea.

PMID: 27229121 [PubMed - indexed for MEDLINE]

Phase I dose-escalation study of the c-Met tyrosine kinase inhibitor SAR125844 in Asian patients with advanced solid tumors, including patients with MET-amplified gastric cancer.

Oncotarget. 2017 Jun 16;:

Authors: Shitara K, Kim TM, Yokota T, Goto M, Satoh T, Ahn JH, Kim HS, Assadourian S, Gomez C, Harnois M, Hamauchi S, Kudo T, Doi T, Bang YJ

Abstract
SAR125844 is a potent and selective inhibitor of the c-Met kinase receptor. This was an open-label, phase I, multicenter, dose-escalation, and dose-expansion trial of SAR125844 in Asian patients with solid tumors, a subgroup of whom had gastric cancer and MET amplification (NCT01657214). SAR125844 was administered by intravenous infusion (260-570 mg/m2) on days 1, 8, 15, and 22 of each 28-day cycle. Objectives were to determine the maximum tolerated dose (MTD) and to evaluate SAR125844 safety and pharmacokinetic profile. Antitumor activity was also assessed. Of 38 patients enrolled (median age 64.0 years), 22 had gastric cancer, including 14 with MET amplification. In the dose-escalation cohort (N = 19; unselected population, including three patients with MET-amplification [two with gastric cancer and one with lung cancer]), the MTD was not reached, and the recommended dose was established at 570 mg/m2. Most frequent treatment-emergent adverse events (AEs) were nausea (36.8%), vomiting (34.2%), decreased appetite (28.9%), and fatigue or asthenia, constipation, and abdominal pains (each 21.1%); none appeared to be dose-dependent. Grade ≥ 3 AEs were observed in 39.5% of patients and considered drug-related in 7.9%. SAR125844 exposure increased slightly more than expected by dose proportionality; dose had no significant effect on clearance. No objective responses were observed in the dose-escalation cohort, with seven patients (three gastric cancer, two colorectal cancer, one breast cancer, and one with cancer of unknown primary origin) having stable disease. Modest antitumor activity was observed at 570 mg/m2 in the dose-expansion cohort, comprising patients with MET-amplified tumors (N = 19). Two gastric cancer patients had partial responses, seven patients had stable disease (six gastric cancer and one kidney cancer), and 10 patients had progressive disease. Single-agent SAR125844 administered up to 570 mg/m2 has acceptable tolerability and modest antitumor activity in patients with MET-amplified gastric cancer.

PMID: 28636538 [PubMed - as supplied by publisher]

Sorafenib in Japanese Patients With Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma.

Thyroid. 2017 Jun 21;:

Authors: Ito Y, Onoda N, Ito KI, Sugitani I, Takahashi S, Yamaguchi I, Kabu K, Tsukada K

Abstract
BACKGROUND: Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan even though vandetanib for MTC, and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). We conducted an uncontrolled, open-label, multicenter, single-arm, phase 2 clinical study to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC.
METHODS: Japanese patients with histologically confirmed ATC and locally advanced or metastatic MTC were enrolled from April to September 2014. The primary endpoint was to evaluate the safety of sorafenib. Treatment efficacy variables including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and maximum reduction in tumor size were evaluated as secondary endpoints. Patients received sorafenib 400 mg orally twice daily on a continuous basis and then continued treatment until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent.
RESULTS: A total of 20 patients were screened and 18, including 8 with MTC and 10 with ATC, were enrolled. The most common drug-related adverse events were palmar-plantar erythrodysesthesia (72%), alopecia (56%), hypertension (56%), and diarrhea (44%). In the ATC patients, median PFS was 2.8 months (95% CI, 0.7-5.6), and median OS was 5.0 months (95% CI, 0.7-5.7); ORR and DCR were 0% and 40%, respectively. In the MTC population, neither median PFS nor OS had been reached at the time of this analysis; ORR was 25% and DCR was 75%.
CONCLUSIONS: The toxicities reported in this study were consistent with the known safety profile of sorafenib. Sorafenib seems to be effective in the treatment of advanced MTC but not ATC and could be a new treatment option for locally advanced or metastatic MTC and RAI-R DTC.

PMID: 28635560 [PubMed - as supplied by publisher]

No blank slates: Pre-existing schemas about pharmaceuticals predict memory for side effects.

Psychol Health. 2017 Apr;32(4):402-421

Authors: Heller MK, Chapman SC, Horne R

Abstract
OBJECTIVES: Attribution of symptoms as medication side effects is informed by pre-existing beliefs about medicines and perceptions of personal sensitivity to their effects (pharmaceutical schemas). We tested whether (1) pharmaceutical schemas were associated with memory (recall/recognition) for side effect information (2) memory explained the attribution of a common unrelated symptom as a side effect.
DESIGN: In this analogue study participants saw the patient leaflet of a fictitious asthma drug listing eight side effects.
MAIN OUTCOME MEASURES: We measured recall and recognition memory for side effects and used a vignette to test whether participants attributed an unlisted common symptom (headache) as a side effect.
RESULTS: Participants who perceived pharmaceuticals as more harmful in general recalled fewer side effects correctly (rCorrect Recall = -.273), were less able to differentiate between listed and unlisted side effects (rRecognition Sensitivity = -.256) and were more likely to attribute the unlisted headache symptom as a side effect (rside effect attribution = .381, ps < .01). The effect of harm beliefs on side effect attribution was partially mediated by correct recall of side effects.
CONCLUSION: Pharmaceutical schemas are associated with memory for side effect information. Memory may explain part of the association between pharmaceutical schemas and the attribution of unrelated symptoms as side effects.

PMID: 28219295 [PubMed - indexed for MEDLINE]

A Study of Acute Poisoning Cases Admitted to the University Hospital Emergency Department in Tabriz, Iran.

Drug Res (Stuttg). 2017 Mar;67(3):183-188

Authors: Oraie M, Hosseini MJ, Islambulchilar M, Hosseini SH, Ahadi-Barzoki M, Sadr H, Yaghoubi H

Abstract
Chemical substances have an important threat due to extensive use in medicine, agriculture, industry and environment. In this retrospective study, etiological and demographic characteristics of acute poisoning cases admitted to a hospital in Iran were investigated. We compared these data with those reported from other parts of the country and the international experiences to evaluate any difference if exists. 7 052 poisoned cases admitted to the hospital from April 2006 to March 2013, by data collected from the medical record in poison center section. According to our results there is a predominance of male patients and the majority of the poisoned patients were between 20-30 years old. Drug poisoning was the most common cause of poisonings. The most frequently involved drugs were benzodiazepines and antidepressants. The seasonal distribution of our study showed a peak in summer. To prevent acute poisonings, the social education about the risk assessment of central nervous system-acting drugs and reduction of the exposure period of people to pesticides are recommended. This study suggested a proper educational program for the public and primary care units. Our results provide useful information for preventive strategies.

PMID: 28073114 [PubMed - indexed for MEDLINE]

Disclosure of Adverse Events in Pediatrics.

Pediatrics. 2016 Dec;138(6):

Authors: COMMITTEE ON MEDICAL LIABILITY AND RISK MANAGEMENT, COUNCIL ON QUALITY IMPROVEMENT AND PATIENT SAFETY

Abstract
Despite increasing attention to issues of patient safety, preventable adverse events (AEs) continue to occur, causing direct and consequential injuries to patients, families, and health care providers. Pediatricians generally agree that there is an ethical obligation to inform patients and families about preventable AEs and medical errors. Nonetheless, barriers, such as fear of liability, interfere with disclosure regarding preventable AEs. Changes to the legal system, improved communications skills, and carefully developed disclosure policies and programs can improve the quality and frequency of appropriate AE disclosure communications.

PMID: 27940747 [PubMed - indexed for MEDLINE]

Systematic Review and Meta-Analysis of Randomised Trials to Ascertain Fatal Gastrointestinal Bleeding Events Attributable to Preventive Low-Dose Aspirin: No Evidence of Increased Risk.

PLoS One. 2016;11(11):e0166166

Authors: Elwood PC, Morgan G, Galante J, Chia JW, Dolwani S, Graziano JM, Kelson M, Lanas A, Longley M, Phillips CJ, Pickering J, Roberts SE, Soon SS, Steward W, Morris D, Weightman AL

Abstract
BACKGROUND: Aspirin has been shown to lower the incidence and the mortality of vascular disease and cancer but its wider adoption appears to be seriously impeded by concerns about gastrointestinal (GI) bleeding. Unlike heart attacks, stroke and cancer, GI bleeding is an acute event, usually followed by complete recovery. We propose therefore that a more appropriate evaluation of the risk-benefit balance would be based on fatal adverse events, rather than on the incidence of bleeding. We therefore present a literature search and meta-analysis to ascertain fatal events attributable to low-dose aspirin.
METHODS: In a systematic literature review we identified reports of randomised controlled trials of aspirin in which both total GI bleeding events and bleeds that led to death had been reported. Principal investigators of studies in which fatal events had not been adequately described were contacted via email and asked for further details. A meta-analyses was then performed to estimate the risk of fatal gastrointestinal bleeding attributable to low-dose aspirin.
RESULTS: Eleven randomised trials were identified in the literature search. In these the relative risk (RR) of 'major' incident GI bleeding in subjects who had been randomised to low-dose aspirin was 1.55 (95% CI 1.33, 1.83), and the risk of a bleed attributable to aspirin being fatal was 0.45 (95% CI 0.25, 0.80). In all the subjects randomised to aspirin, compared with those randomised not to receive aspirin, there was no significant increase in the risk of a fatal bleed (RR 0.77; 95% CI 0.41, 1.43).
CONCLUSIONS: The majority of the adverse events caused by aspirin are GI bleeds, and there appears to be no valid evidence that the overall frequency of fatal GI bleeds is increased by aspirin. The substantive risk for prophylactic aspirin is therefore cerebral haemorrhage which can be fatal or severely disabling, with an estimated risk of one death and one disabling stroke for every 1,000 people taking aspirin for ten years. These adverse effects of aspirin should be weighed against the reductions in vascular disease and cancer.

PMID: 27846246 [PubMed - indexed for MEDLINE]

Eliciting the child's voice in adverse event reporting in oncology trials: Cognitive interview findings from the Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events initiative.

Pediatr Blood Cancer. 2017 Mar;64(3):

Authors: Reeve BB, McFatrich M, Pinheiro LC, Weaver MS, Sung L, Withycombe JS, Baker JN, Mack JW, Waldron MK, Gibson D, Tomlinson D, Freyer DR, Mowbray C, Jacobs S, Palma D, Martens CE, Gold SH, Jackson KD, Hinds PS

Abstract
BACKGROUND: Adverse event (AE) reporting in oncology trials is required, but current practice does not directly integrate the child's voice. The Pediatric Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being developed to assess symptomatic AEs via child/adolescent self-report or proxy-report. This qualitative study evaluates the child's/adolescent's understanding and ability to provide valid responses to the PRO-CTCAE to inform questionnaire refinements and confirm content validity.
PROCEDURE: From seven pediatric research hospitals, children/adolescents ages 7-15 years who were diagnosed with cancer and receiving treatment were eligible, along with their parent-proxies. The Pediatric PRO-CTCAE includes 130 questions that assess 62 symptomatic AEs capturing symptom frequency, severity, interference, or presence. Cognitive interviews with retrospective probing were completed with children in the age groups of 7-8, 9-12, and 13-15 years. The children/adolescents and proxies were interviewed independently.
RESULTS: Two rounds of interviews involved 81 children and adolescents and 74 parent-proxies. Fifteen of the 62 AE terms were revised after Round 1, including refinements to the questions assessing symptom severity. Most participants rated the PRO-CTCAE AE items as "very easy" or "somewhat easy" and were able to read, understand, and provide valid responses to questions. A few AE items assessing rare events were challenging to understand.
CONCLUSIONS: The Pediatric and Proxy PRO-CTCAE performed well among children and adolescents and their proxies, supporting its content validity. Data from PRO-CTCAE may improve symptomatic AE reporting in clinical trials and enhance the quality of care that children receive.

PMID: 27650708 [PubMed - indexed for MEDLINE]

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