Related Articles

Evaluation of different recall periods for the US National Cancer Institute's PRO-CTCAE.

Clin Trials. 2017 Jun;14(3):255-263

Authors: Mendoza TR, Dueck AC, Bennett AV, Mitchell SA, Reeve BB, Atkinson TM, Li Y, Castro KM, Denicoff A, Rogak LJ, Piekarz RL, Cleeland CS, Sloan JA, Schrag D, Basch E

Abstract
AIMS: The US National Cancer Institute recently developed the PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events). PRO-CTCAE is a library of questions for clinical trial participants to self-report symptomatic adverse events (e.g. nausea). The objective of this study is to inform evidence-based selection of a recall period when PRO-CTCAE is included in a trial. We evaluated differences between 1-, 2-, 3-, and 4-week recall periods, using daily reporting as the reference.
METHODS: English-speaking patients with cancer receiving chemotherapy and/or radiotherapy were enrolled at four US cancer centers and affiliated community clinics. Participants completed 27 PRO-CTCAE items electronically daily for 28 days, and then weekly over 4 weeks, using 1-, 2-, 3-, and 4-week recall periods. For each recall period, mean differences, effect sizes, and intraclass correlation coefficients were calculated to evaluate agreement between the maximum of daily ratings and the corresponding ratings obtained using longer recall periods (e.g. maximum of daily scores over 7 days vs 1-week recall). Analyses were repeated using the average of daily scores within each recall period rather than the maximum of daily scores.
RESULTS: A total of 127 subjects completed questionnaires (57% male; median age: 57). The median of the 27 mean differences in scores on the PRO-CTCAE 5-point response scale comparing the maximum daily versus the longer recall period (and corresponding effect size) was -0.20 (-0.20) for 1-week recall, -0.36 (-0.31) for 2-week recall, -0.45 (-0.39) for 3-week recall, and -0.47 (-0.40) for 4-week recall. The median intraclass correlation across 27 items between the maximum of daily ratings and the corresponding longer recall ratings for 1-week recall was 0.70 (range: 0.54-0.82), for 2-week recall was 0.74 (range: 0.58-0.83), for 3-week recall was 0.72 (range: 0.61-0.84), and for 4-week recall was 0.72 (range: 0.64-0.86). Similar results were observed for all analyses using the average of daily scores rather than the maximum of daily scores.
CONCLUSION: A 1-week recall corresponds best to daily reporting. Although intraclass correlations remain stable over time, there are small but progressively larger differences between daily and longer recall periods at 2, 3, and 4 weeks, respectively. The preferred recall period for the PRO-CTCAE is the past 7 days, although investigators may opt for recall periods of 2, 3, or 4 weeks with an understanding that there may be some information loss.

PMID: 28545337 [PubMed - indexed for MEDLINE]

Related Articles

Role of taxanes in chemotherapy-related cognitive impairment: A prospective longitudinal study.

Breast Cancer Res Treat. 2017 Jul;164(1):179-187

Authors: Cerulla N, Arcusa À, Navarro JB, Garolera M, Enero C, Chico G, Fernández-Morales L

Abstract
PURPOSE: The aim of this study is to elucidate the role of taxanes on cognition when they are administered as a part of the treatment with a fluorouracil, epirubicin and cyclophosphamide (FEC) regimen for breast cancer (BC).
METHODS: Two groups of women (n = 51) with a novel diagnostic of BC that were treated with a combination of FEC alone (6 cycles of FEC) or with taxanes (4 cycles of FEC plus 8 cycles of taxanes) were compared at three moments: before chemotherapy, after its completion (short-term evaluation) and at a mean of 74.5 weeks from baseline as a long-term evaluation.
RESULTS: Both groups showed worsening in tests of attention and executive functions on the short-term assessment, with the group treated with taxanes showing more number of affected cognitive measures at this time point, including verbal learning and speed measures. At the long-term evaluation, cognitive dysfunction was still found in attention and executive functions in both groups.
CONCLUSION: Our results suggest that chemotherapy for BC with a FEC regimen can have a negative effect on cognition. Acute deficits seem to be larger when taxanes are added, but treatment seems to affect cognition also at long term.

PMID: 28421379 [PubMed - indexed for MEDLINE]

Related Articles

Frailty and long-term mortality of older breast cancer patients: CALGB 369901 (Alliance).

Breast Cancer Res Treat. 2017 Jul;164(1):107-117

Authors: Mandelblatt JS, Cai L, Luta G, Kimmick G, Clapp J, Isaacs C, Pitcher B, Barry W, Winer E, Sugarman S, Hudis C, Muss H, Cohen HJ, Hurria A

Abstract
PURPOSE: Breast cancer patients aged 65+ ("older") vary in frailty status. We tested whether a deficits accumulation frailty index predicted long-term mortality.
METHODS: Older patients (n = 1280) with non-metastatic, invasive breast cancer were recruited from 78 Alliance sites from 2004 to 2011, with follow-up to 2015. Frailty categories (robust, pre-frail, and frail) were based on 35 baseline illness and function items. Cox proportional hazards and competing risk models were used to calculate all-cause and breast cancer-specific mortality for up to 7 years, respectively. Potential covariates included demographic, psychosocial, and clinical factors, diagnosis year, and care setting.
RESULTS: Patients were 65-91 years old. Most (76.6%) were robust; 18.3% were pre-frail, and 5.1% frail. Robust patients tended to receive more chemotherapy ± hormonal therapy (vs. hormonal) than pre-frail or frail patients (45% vs. 37 and 36%, p = 0.06), and had the highest adherence to hormonal therapy. The adjusted hazard ratios for all-cause mortality (n = 209 deaths) were 1.7 (95% CI 1.2-2.4) and 2.4 (95% CI 1.5-4.0) for pre-frail and frail versus robust women, respectively, with an absolute mortality difference of 23.5%. The adjusted hazard of breast cancer death (n-99) was 3.1 (95% CI 1.6-5.8) times higher for frail versus robust patients (absolute difference of 14%). Treatment differences did not account for the relationships between frailty and mortality.
CONCLUSIONS: Most older breast cancer patients are robust and could consider chemotherapy where otherwise indicated. Patients who are frail or pre-frail have elevated long-term all-cause and breast cancer mortality. Frailty indices could be useful for treatment decision-making and care planning with older patients.

PMID: 28364214 [PubMed - indexed for MEDLINE]

Notice NOT-HL-18-607 from the NIH Guide for Grants and Contracts

Notice NOT-PM-18-002 from the NIH Guide for Grants and Contracts

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pharmacogenomics

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"systems biology"

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("drug-induced" OR "drug-related") AND ("adverse events" OR "side effects" OR "side-effects")

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Funding Opportunity PA-18-713 from the NIH Guide for Grants and Contracts. The National Institutes of Health (NIH) Office of the Director announces the availability of administrative supplements to expand existing research to focus on Sexual and Gender Minority (SGM) health. Principal Investigators holding specific types of NIH research grants, listed in the full Funding Opportunity Announcement (FOA) are notified that funds may be available for administrative supplements to meet increased costs that are within the scope of the approved award, but that were unforeseen when the new or renewal application or grant progress report for non-competing continuation support was submitted. Applications for administrative supplements are considered prior approval requests (as described in Section 8.1.2.11 of the NIH Grants Policy Statement) and will be routed directly to the Grants Management Officer of the parent award. Although requests for administrative supplements may be submitted through this FOA, there is no guarantee that funds are available from the awarding IC or for any specific grant. All applicants are encouraged to discuss potential requests with the awarding IC. Additionally, prior to submission, applicants must review the awarding IC's web site to ensure they meet the IC's requirements. SGM populations include, but are not limited to, lesbian, gay, bisexual, and transgender people, and individuals with differences or disorders of sexual development (sometimes referred to as intersex or as specific diagnoses). This trans-NIH effort, which involves multiple Institutes, Centers and Offices from across NIH, is intended to encourage investigation in this growing, field of research. To increase our collective understanding of the broad range of research needed to address the unique health issues of SGM populations, the supplement will focus on areas of research interest, including, but not limited to: studies on increased disease risk; mental, behavioral and social health; approaches to personalized medicine; access to care; reprod

Notice NOT-NS-18-050 from the NIH Guide for Grants and Contracts

Funding Opportunity RFA-FD-18-015 from the NIH Guide for Grants and Contracts. The FDA Center for Drug Evaluation and Research is encouraging applications for projects to expedite development of data standards and terminologies to support human drug development and evaluation. The primary objective is to support research and the development of non-proprietary, consensus-based, national data standards for use in clinical studies of human drugs and biologics. Projects may focus on solutions to general data standards development and implementation challenges or on specific clinical concepts, domains, or therapeutic areas where standardization is needed.

Funding Opportunity PAR-18-712 from the NIH Guide for Grants and Contracts. The purpose of this Funding Opportunity Announcement (FOA) is to advance the discovery and characterization of primary immunodeficiency diseases, to understand the causes and mechanisms of disease, to enable early detection and molecular diagnosis, and to support the development of strategies to treat and eventually cure these disorders.

Cooperative recruitment of Yan via a high-affinity ETS supersite organizes repression to confer specificity and robustness to cardiac cell fate specification.

Genes Dev. 2018 Mar 13;:

Authors: Boisclair Lachance JF, Webber JL, Hong L, Dinner A, Rebay I

Abstract
Cis-regulatory modules (CRMs) are defined by unique combinations of transcription factor-binding sites. Emerging evidence suggests that the number, affinity, and organization of sites play important roles in regulating enhancer output and, ultimately, gene expression. Here, we investigate how the cis-regulatory logic of a tissue-specific CRM responsible for even-skipped (eve) induction during cardiogenesis organizes the competing inputs of two E-twenty-six (ETS) members: the activator Pointed (Pnt) and the repressor Yan. Using a combination of reporter gene assays and CRISPR-Cas9 gene editing, we suggest that Yan and Pnt have distinct syntax preferences. Not only does Yan prefer high-affinity sites, but an overlapping pair of such sites is necessary and sufficient for Yan to tune Eve expression levels in newly specified cardioblasts and block ectopic Eve induction and cell fate specification in surrounding progenitors. Mechanistically, the efficient Yan recruitment promoted by this high-affinity ETS supersite not only biases Yan-Pnt competition at the specific CRM but also organizes Yan-repressive complexes in three dimensions across the eve locus. Taken together, our results uncover a novel mechanism by which differential interpretation of CRM syntax by a competing repressor-activator pair can confer both specificity and robustness to developmental transitions.

PMID: 29535190 [PubMed - as supplied by publisher]

Funding Opportunity RFA-HL-19-016 from the NIH Guide for Grants and Contracts. This FOA encourages new R43 applications for design and development of technologies to monitor health or deliver care in a real-time, accessible, effective, and minimally obtrusive way for aging adults. These may be novel sensor or monitoring systems, home-use point-of-care devices, home or mobile therapy or rehabilitation tools, or information systems and should have the goal of fostering healthy and independent living. The development of such technologies should incorporate specific human factors for people with disabilities, people aging with mild impairments, as well as individuals with chronic conditions. Technology usability for these populations must be incorporated into the design early. Usability considerations include but are not limited to patient-facing displays, hearing and visual impairments considerations, tactile limitations, and literacy. These improvements in technology design could yield more accurate and earlier detection of changes that may interfere with healthy and independent living for older adults.

Notice NOT-GM-18-021 from the NIH Guide for Grants and Contracts

Notice NOT-DC-18-006 from the NIH Guide for Grants and Contracts

Funding Opportunity PAR-18-710 from the NIH Guide for Grants and Contracts. The objective of the NIH Career Transition Award (K22) is to provide support to outstanding basic or clinical investigators to develop their independent research skills through a two phase program: an initial period involving an intramural appointment at the NIH and a final period of support at an extramural institution. This NINDS K22 is specifically designed to facilitate the transition of NINDS intramural neurologist- and neurosurgeon-scientists to independent, academic faculty positions that support clinician-scientists to engage in independently funded scientific research as well as clinical activities.

Funding Opportunity PAR-18-711 from the NIH Guide for Grants and Contracts. The objective of the NIH Career Transition Award (K22) is to provide support to outstanding basic or clinical investigators to develop their independent research skills through a two phase program: an initial period involving an intramural appointment at the NIH and a final period of support at an extramural institution. This NINDS K22 is specifically designed to facilitate the transition of NINDS intramural neurologist- and neurosurgeon-scientists to independent, academic faculty positions that support clinician-scientists to engage in independently funded scientific research as well as clinical activities.

Scedosporium and Lomentospora: an updated overview of underrated opportunists.

Med Mycol. 2018 Apr 01;56(suppl_1):102-125

Authors: Ramirez-Garcia A, Pellon A, Rementeria A, Buldain I, Barreto-Bergter E, Rollin-Pinheiro R, de Meirelles JV, Xisto MIDS, Ranque S, Havlicek V, Vandeputte P, Govic YL, Bouchara JP, Giraud S, Chen S, Rainer J, Alastruey-Izquierdo A, Martin-Gomez MT, López-Soria LM, Peman J, Schwarz C, Bernhardt A, Tintelnot K, Capilla J, Martin-Vicente A, Cano-Lira J, Nagl M, Lackner M, Irinyi L, Meyer W, de Hoog S, Hernando FL

Abstract
Species of Scedosporium and Lomentospora are considered as emerging opportunists, affecting immunosuppressed and otherwise debilitated patients, although classically they are known from causing trauma-associated infections in healthy individuals. Clinical manifestations range from local infection to pulmonary colonization and severe invasive disease, in which mortality rates may be over 80%. These unacceptably high rates are due to the clinical status of patients, diagnostic difficulties, and to intrinsic antifungal resistance of these fungi. In consequence, several consortia have been founded to increase research efforts on these orphan fungi. The current review presents recent findings and summarizes the most relevant points, including the Scedosporium/Lomentospora taxonomy, environmental distribution, epidemiology, pathology, virulence factors, immunology, diagnostic methods, and therapeutic strategies.

PMID: 29538735 [PubMed - in process]