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https://www.readbyqxmd.com/read/28550039/a-phase-1-2-study-of-the-oral-proteasome-inhibitor-ixazomib-in-relapsed-or-refractory-light-chain-al-amyloidosis
#1
Vaishali Sanchorawala, Giovanni Palladini, Vishal Kukreti, Jeffrey A Zonder, Adam D Cohen, David C Seldin, Angela Dispenzieri, Arnaud Jaccard, Stefan O Schönland, Deborah Berg, Huyuan Yang, Neeraj Gupta, Ai-Min Hui, Raymond L Comenzo, Giampaolo Merlini
This phase 1/2 study assessed the safety, tolerability, and preliminary efficacy of the oral proteasome inhibitor (PI) ixazomib in patients with relapsed/refractory AL amyloidosis (RRAL). Ixazomib was administered to adult patients with RRAL after ≥1 prior line of therapy (including bortezomib) on days 1, 8, and 15 of 28-day cycles, for up to 12 cycles. Patients with less than partial response after 3 cycles received oral dexamethasone (40 mg, days 1-4) from cycle 4. A 3+3 dose-escalation phase was followed by 2 expansion cohorts (PI-naïve and PI-exposed patients) at the maximum tolerated dose (MTD)...
May 26, 2017: Blood
https://www.readbyqxmd.com/read/28549459/-a-steep-learning-curve-junior-doctor-perspectives-on-the-transition-from-medical-student-to-the-health-care-workplace
#2
Nancy Sturman, Zachary Tan, Jane Turner
BACKGROUND: The transition from medical student to hospital-based first year junior doctor (termed "intern" in Australia) is known to be challenging, and recent changes in clinical learning environments may reduce graduate preparedness for the intern workplace. Although manageable challenges and transitions are a stimulus to learning, levels of burnout in junior medical colleagues are concerning. In order to prepare and support medical graduates, educators need to understand contemporary junior doctor perspectives on this transition...
May 26, 2017: BMC Medical Education
https://www.readbyqxmd.com/read/28548223/cannabis-smoking-and-cardiovascular-health-it-s-complicated
#3
M R Piano
Many states have legalized cannabis use for treatment of certain medical conditions or have legalized cannabis for recreational use. Consequently, cannabis use prevalence has escalated, giving rise to concerns about potential health effects. Cannabis smoking remains the most prevalent route of administration and is associated with inhalation of chemical toxicants. The aim of this article is to summarize the effects of cannabis smoking on the vasculature and occurrence of cardiovascular (CV) events such as myocardial infarction (MI) and stroke...
May 26, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28548028/developmental-differences-between-newborn-and-adult-mice-in-response-to-romiplostim
#4
Katherine A Sparger, Haley Ramsey, Viola Lorenz, Zhi-Jian Liu, Henry A Feldman, Nan Li, Tahirih Laforest, Martha C Sola-Visner
Thrombocytopenia is frequent among sick neonates. While most cases are transient, some neonates experience prolonged and severe thrombocytopenia. These infants often pose diagnostic and therapeutic challenges, and may receive large numbers of platelet transfusions. Romiplostim (ROM) is a thrombopoietin (TPO)-receptor-agonist approved for treatment of adults with chronic immune thrombocytopenia (ITP). The immature platelet fraction (IPF) is a novel measure of newly produced platelets, which could aid with the diagnostic evaluation of thrombocytopenic neonates...
May 26, 2017: Platelets
https://www.readbyqxmd.com/read/28547854/nucleus-accumbens-functional-connectivity-at-age-20-is-associated-with-trajectory-of-adolescent-cannabis-use-and-predicts-psychosocial-functioning-in-young-adulthood
#5
Sarah D Lichenstein, Samuel Musselman, Daniel S Shaw, Stephanie Sitnick, Erika E Forbes
AIMS: To identify trajectories of cannabis use across adolescence, 2) to measure the influence of cannabis use characteristics on functional connectivity of the nucleus accumbens (NAcc), and 3) to assess whether patterns of functional connectivity related to cannabis use are associated with psychosocial functioning 2 years later. DESIGN: The Pitt Mother & Child Project (PMCP) is a prospective, longitudinal study of male youth at high risk for psychopathology based on family income and gender...
May 26, 2017: Addiction
https://www.readbyqxmd.com/read/28546381/adjunct-therapies-for-refractory-status-asthmaticus-in-children
#6
Kyle J Rehder
Asthma exacerbation is a common reason for children to present to the emergency department. If primary therapies fail to halt the progression of an asthma flare, status asthmaticus often leads to hospital, and potentially ICU, admission. Following the initial administration of inhaled β agonists and systemic corticosteroids, a wide array of adjunct medical therapies may be used to treat status asthmaticus. Unfortunately, the data supporting the use of these adjunct therapies are often unclear, conflicting, or absent...
June 2017: Respiratory Care
https://www.readbyqxmd.com/read/28546227/keyboard-a-novel-bayesian-toxicity-probability-interval-design-for-phase-i-clinical-trials
#7
Fangrong Yan, Sumithra J Mandrekar, Ying Yuan
The primary objective of phase I oncology trials is to find the maximum tolerated dose (MTD). The 3+3 design is easy to implement but performs poorly in finding the MTD. A newer design, such as the modified toxicity probability interval (mTPI) design, provides better accuracy to identify the MTD but tends to overdose patients. We propose the keyboard design, an intuitive Bayesian design that conducts dose escalation and de-escalation based on whether the strongest key, defined as the dosing interval that most likely contains the current dose, is below or above the target dosing interval...
May 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28545679/selective-use-of-radioactive-iodine-rai-in-thyroid-cancer-no-longer-one-size-fits-all
#8
REVIEW
J L Marti, L G T Morris, A S Ho
A remarkable, evidence-based trend toward de-escalation has reformed the practice of radioactive iodine (RAI) administration for thyroid cancer patients. Updated guidelines have supported both decreased RAI doses for select populations, as well as expanded definitions of low-risk and intermediate-risk patients that may not require RAI. Correspondingly, there is now increased flexibility for hemithyroidectomy without need for RAI, and relaxed TSH suppression targets for low-risk thyroidectomy patients. Clinical judgment remains indispensable where multiple risk factors co-exist that individually are not indications for RAI...
May 3, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28545456/towards-an-equitable-healthcare-in-china-evaluating-the-productive-efficiency-of-community-health-centers-in-jiangsu-province
#9
Lulin Zhou, Xinglong Xu, Henry Asante Antwi, Linna Wang
BACKGROUND: While the demand for the health service keeps escalating at the grass root or rural areas of China, a substantial portion of healthcare resources remains stagnant in the more developed cities and this has entrenched health inequity in many parts of China. At its conception, the Deepening Health Care Reform in 2012 China was intended to flush out these discrepancies and promote a more equitable and efficient distribution of health resources. Nearly half a decade of this reform, there are uncertainties as to whether the attainment of the objectives of the reform is in sight...
May 25, 2017: International Journal for Equity in Health
https://www.readbyqxmd.com/read/28544774/safety-pharmacokinetics-and-pharmacodynamics-of-hetrombopag-olamine-a-novel-tpo-r-agonist-in-healthy-subjects
#10
Li Zheng, Mao-Zhi Liang, Xiao-Ling Zeng, Cai-Zheng Li, Yi-Fan Zhang, Xiao-Yan Chen, Xi Zhu, An-Bo Xiang
Hetrombopag olamine (hetrombopag) is a novel small-molecule, orally bioavailable, non-peptide thrombopoietin (TPO) receptor agonist that is being developed as the treatment for thrombocytopenia. Two randomized, placebo-controlled phase I studies were conducted in 72 healthy subjects to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of hetrombopag. Hetrombopag was orally administered with a single dose in 5 dose cohorts (5 mg, 10 mg, 20 mg, 30 mg or 40 mg) in the first study, and given once daily for 10 days in 3 dose cohorts (2...
May 24, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28544644/%C3%AE-cell-function-in-postmenopausal-women-with-isolated-postchallenge-hyperglycemia
#11
Chii-Min Hwu, Yi-Chun Lin, Kuan-Hung Lin
BACKGROUND: Isolated postchallenge hyperglycemia (IPH) is an early stage of type 2 diabetes mellitus (T2DM) with fasting glucose < 126 mg/dL and 2 h glucose ≥ 200 mg/dL. Observations of insulin secretion profile in subjects with IPH may provide insight to the pathogenesis of T2DM in older women. METHODS: We recruited 555 naturally postmenopausal women without a history of T2DM for this study. All participants received a 75 g oral glucose tolerance test to examine if they had IPH...
May 22, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28544175/prevalence-and-potential-factors-associated-with-overweight-and-obesity-status-in-adults-with-intellectual-developmental-disorders
#12
REVIEW
Sobhana Ranjan, Jennifer A Nasser, Kathleen Fisher
BACKGROUND: The prevalence of being overweight and obese is increasing not just in the general population but also in individuals with intellectual disability (ID). Therefore, a need to identify factors contributing to overweight/obesity arises as this population is escalating. MATERIALS AND METHODS: This narrative review article summarizes pertinent research focusing on prevalence and the potential factors associated with overweight and obesity in adults with intellectual disability during the past decade...
May 24, 2017: Journal of Applied Research in Intellectual Disabilities: JARID
https://www.readbyqxmd.com/read/28542711/preventing-relapse-after-haematopoietic-stem-cell-transplantation-for-acute-leukaemia-the-role-of-post-transplantation-minimal-residual-disease-mrd-monitoring-and-mrd-directed-intervention
#13
REVIEW
Xiao-Dong Mo, Meng Lv, Xiao-Jun Huang
Relapse is the main cause of treatment failure after allogeneic haematopoietic stem cell transplantation (allo-HSCT) for acute leukaemia (AL). Post-transplantation minimal residual disease (MRD) monitoring enables risk stratification and identifies AL patients at higher risk of relapse. MRD assessment primarily involves the determination of leukaemia-associated immunophenotypic patterns using multiparameter flow cytometry, and the polymerase chain reaction (PCR)-based evaluation of expression levels of leukaemia-related genes (specific reciprocal gene rearrangements and other mutation types)...
May 23, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28542412/low-rates-of-antibiotic-resistance-and-infectious-mortality-in-a-cohort-of-high-risk-hematology-patients-a-single-center-retrospective-analysis-of-blood-stream-infection
#14
Jason R Conn, Elizabeth M Catchpoole, Naomi Runnegar, Sally J Mapp, Kate A Markey
Febrile neutropenia (FN) is a medical emergency and can represent a life-threatening complication for hematology patients treated with intensive chemotherapy regimens. In clinical practice, the diagnostic yield of blood cultures and other investigations which aim to identify a causative organism or site of infection is low. We have retrospectively examined all blood cultures collected in a "real world" cohort of patients receiving chemotherapy for acute leukemia and patients with aggressive lymphoma treated with Hyper-CVAD/MTX-cytarabine, at a single tertiary center over a five-year period...
2017: PloS One
https://www.readbyqxmd.com/read/28542389/cognitive-distortions-among-older-adult-gamblers-in-an-asian-context
#15
Mythily Subramaniam, Siow Ann Chong, Colette Browning, Shane Thomas
AIMS: The study aims to describe the construct of cognitive distortions based on the narratives of older adult gamblers (aged 60 years and above) in Singapore. METHODS: Singapore residents (citizens or permanent residents) aged 60 years and above, who were current or past regular gamblers were included in the study. Participants were recruited using a combination of venue based approach, referrals from service providers as well as by snowball sampling. In all, 25 in-depth interviews were conducted with older adult gamblers...
2017: PloS One
https://www.readbyqxmd.com/read/28541603/comparison-of-first-line-chemotherapy-including-escalated-beacopp-versus-chemotherapy-including-abvd-for-people-with-early-unfavourable-or-advanced-stage-hodgkin-lymphoma
#16
REVIEW
Nicole Skoetz, Andrea Will, Ina Monsef, Corinne Brillant, Andreas Engert, Bastian von Tresckow
BACKGROUND: There are two different international standards for the treatment of early unfavourable and advanced stage Hodgkin lymphoma (HL): chemotherapy with escalated BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) regimen and chemotherapy with ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) regimen. OBJECTIVES: To determine the advantages and disadvantages of chemotherapy including escalated BEACOPP compared to chemotherapy including ABVD in the treatment of early unfavourable or advanced stage HL as first-line treatment...
May 25, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28541507/current-management-and-clinical-outcomes-for-catheter-ablation-of-atrioventricular-nodal-re-entrant-tachycardia
#17
Jonathan Chrispin, Satish Misra, Joseph E Marine, John Rickard, Andreas Barth, Aravindan Kolandaivelu, Hiroshi Ashikaga, Harikrishna Tandri, David D Spragg, Jane Crosson, Ronald D Berger, Gordon Tomaselli, Hugh Calkins, Sunil K Sinha
Aims: Historical studies of ablation of atrioventricular nodal re-entrant tachycardia (AVNRT) have shown high long-term success rates and low complication rates. The potential impact of several recent practice trends has not been described. This study aims to characterize recent clinical practice trends in AVNRT ablation and their associated success rates and complications. Methods and results: Patients undergoing initial ablation of AVNRT between 1 July 2005 and 30 June 2015 were included in this study...
May 24, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28541431/emerging-safety-of-intramedullary-transplantation-of-human-neural-stem-cells-in-chronic-cervical-and-thoracic-spinal-cord-injury
#18
Allan D Levi, David O Okonkwo, Paul Park, Arthur L Jenkins, Shekar N Kurpad, Ann M Parr, Aruna Ganju, Bizhan Aarabi, Dong Kim, Steven Casha, Michael G Fehlings, James S Harrop, Kim D Anderson, Allyson Gage, Jane Hsieh, Stephen Huhn, Armin Curt, Raphael Guzman
BACKGROUND: Human central nervous system stem cells (HuCNS-SC) are multipotent adult stem cells with successful engraftment, migration, and region-appropriate differentiation after spinal cord injury (SCI). OBJECTIVE: To present data on the surgical safety profile and feasibility of multiple intramedullary perilesional injections of HuCNS-SC after SCI. METHODS: Intramedullary free-hand (manual) transplantation of HuCNS-SC cells was performed in subjects with thoracic (n = 12) and cervical (n = 17) complete and sensory incomplete chronic traumatic SCI...
May 24, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28540417/monitoring-early-response-to-chemoradiotherapy-with-18-f-fmiso-dynamic-pet-in-head-and-neck-cancer
#19
Milan Grkovski, Nancy Y Lee, Heiko Schöder, Sean D Carlin, Bradley J Beattie, Nadeem Riaz, Jonathan E Leeman, Joseph A O'Donoghue, John L Humm
PURPOSE: There is growing recognition that biologic features of the tumor microenvironment affect the response to cancer therapies and the outcome of cancer patients. In head and neck cancer (HNC) one such feature is hypoxia. We investigated the utility of (18)F-fluoromisonidazole (FMISO) dynamic positron emission tomography (dPET) for monitoring the early microenvironmental response to chemoradiotherapy in HNC. EXPERIMENTAL DESIGN: Seventy-two HNC patients underwent FMISO dPET scans in a customized immobilization mask (0-30 min dynamic acquisition, followed by 10 min static acquisitions starting at ∼95 min and ∼160 min post-injection) at baseline and early into treatment where patients have already received one cycle of chemotherapy and anywhere from five to ten fractions of 2 Gy per fraction radiation therapy...
May 24, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28540172/nonlinear-relationship-between-enteric-coated-mycophenolate-sodium-dose-and-mycophenolic-acid-exposure-in-han-kidney-transplantation-recipients
#20
Jun Zhang, Mengmeng Jia, Lihua Zuo, Na Li, Yonggang Luo, Zhi Sun, Xiaojian Zhang, Zhenfeng Zhu
The aim of the research was to investigate the pharmacokinetics (PK) of enteric-coated mycophenolate sodium (EC-MPS) by quantification of the active metabolite of mycophenolic acid (MPA) after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from 0 to 12 h after EC-MPS administration...
May 2017: Acta Pharmaceutica Sinica. B
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