tbuckley/cabot-search huggingface dataset:
The impact of infection on health-related quality of life (HRQoL) in patients with Philadelphia negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (Ph- R/R BCP ALL) in a randomized, open-label, phase 3 study (TOWER).
Authors: Andre C. Schuh, Yan Li, Max S. Topp, Xinke Zhang, Paul Cannell, Herve Dombret, Johan Maertens, Anthony Selwyn Stein, Janet Franklin
Journal: Journal of Clinical Oncology (2019)

e18511 Background: In the phase 3 TOWER study (NCT02013167), blinatumomab (BLIN) significantly improved overall survival in adults with Ph- R/R BCP ALL, and these patients (pts) also reported better HRQoL (EORTC QLQ-C30 measures) compared with standard of care (SOC) chemotherapy. This analysis assessed the impact of grade 3+ infection, which was reported in 34.1% of BLIN pts vs 52.3% of SOC pts, on HRQoL in TOWER. Methods: Pts were stratified into two groups: those with infection vs those without infection, between baseline and Day 8, Day 15, and Day 29. A difference-in-difference (DID) model investigated the impact of infection on HRQoL. A 5-point change is considered the minimum clinically important difference in the EORTC QLQ-C30 for between group comparisons (King et al. 1996). Results: In total, 342 pts (n = 247 BLIN; n = 95 SOC) had a non-missing baseline and ≥1 post-baseline HRQoL score for any scale. Grade 3+ infection was reported in 15 (4.5%) pts before Day 8, 49 (14.5%) pts before Day 15, and 76 (22.6%) pts before Day 29. Pts with grade 3+ infection reported clinical meaningful deterioration in global health status (GHS) score and in almost all functional subscales across timepoints assessed (Table). At Day 29, grade 3+ infection was associated with statistically significant and clinically meaningful deterioration in GHS and most functional scales (Table). Similar but smaller effects were also observed for symptom scales/items (data not shown). Conclusions: Grade 3+ infection in pts with Ph- R/R BCP ALL was associated with clinically meaningful deterioration in HRQoL. The lower incidence of infection in pts treated with BLIN vs SOC may have contributed to the improved HRQoL for pts treated with BLIN. Clinical trial information: NCT02013167. [Table: see text]
Comparison of PEG-rhG-CSF and common rhG-CSF after induction chemotherapy in patients with newly diagnosed acute myeloid leukemia.
Authors: Kaiqi Liu, Hui Wei, Ying Wang, Yingchang Mi, Jianxiang Wang
Journal: Journal of Clinical Oncology (2019)

e18507 Background: To compare the PEG-rhG-CSF (brand name:jinyouli) with ordinary rhG-CSF in the myelosuppressive phase after induction chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients promotes the recovery of neutrophils. At the same time, the effects of the two drugs on the incidence of infection and hospitalization were compared. Methods: A prospective randomized controlled trial was conducted in which patients with newly diagnosed AML who met the enrollment criteria were randomized into 1:1 groups: 1. PEG-rhG-CSF group: patients ≥45 kg for 6 mg/time, &lt;45 kg for 3 mg/time, subcutaneous injection once on the 5th day after stopping chemotherapy; 2. rhG-CSF group: 5 μg/kg/day until neutrophils count ≥0.5×10 9 /L and/or leukocytes count ≥1.0×10 9 /L. The neutrophil recovery time (duration from day 1 of chemotherapy to neutrophils count ≥0.5×10 9 /L and/or leukocytes count ≥1.0×10 9 /L), infection rate and hospitalization time were collected from the two groups, and the two groups were analyzed and compared using SAS 9.4. Results: From August 2014 to December 2017, 60 patients with newly diagnosed AML were enrolled: 30 patients in the PEG-rhG-CSF group and 30 patients in the rhG-CSF group. Except for the gender composition (P=0.018), there were no significant differences in age, chemotherapy regimen, neutrophils count before chemotherapy, leukocytes count before chemotherapy, and induction efficacy between the two groups. The median time (range) of neutrophils recovery in patients with PEG-rhG-CSF and rhG-CSF was 19 (14-35) days and 19 (15-26) days, P=0.36. The number of patients (ratio) with infection during neutropenia in the PEG-rhG-CSF group and the rhG-CSF group were 27 (90.0%) and 28 (93.3%), P=1. The median length of hospitalization (range) was 20.5 (17-49) days and 21 (19-43) days, P=0.53. Conclusions: In patients with AML induction chemotherapy, there was no significant difference between the application of PEG-rhG-CSF and daily rhG-CSF in neutrophil recovery time, infection incidence and hospitalization time.
Taking the Mountain to Muhammad
Authors: Margaret Tempero
Journal: Journal of the National Comprehensive Cancer Network (2019)

Taking the Mountain to Muhammad E very time I consider offering a clinical trial to one of my patients, a swirl of concerns goes through my head.As you know, I provide care for patients with pancreatic cancer, who are often terrified about their future.To participate in a clinical trial-as if they don't already have enough to worry about-they must deal with complicated consent forms and procedures, concerning side effects, and even the possibility of being selected for treatment with a placebo.Yikes!Then, if they do participate, they will probably need additional testing, imaging, and sample collection.That means they must make more trips-likely across one of our Bay Area bridges-face traffic gridlock, and pay exorbitant parking fees in the city each time.No wonder national clinical trial accrual rates are low!So while at a recent FDA meeting, I was excited to sit in on a discussion of decentralized clinical trials-a mechanism designed to keep the patient at home as much as possible.Brilliant!Of course, I initially had no idea how that was possible, but the more I learned, the more I liked the concept.Basically, it's simple: mobile clinical teams, physician-led and part of the investigator team, perform home visits, make assessments, and collect biospecimens like skin biopsies, blood, and urine.In some settings, home infusions are even possible.Pair that with telehealth visits as needed, and add in patient-reported outcomes, and now we're rolling!This is already happening, and for some clinical conditions, such as skin conditions (even limited basal cell and squamous cell cancers), the initial evaluation and informed consent can occur at a patient's home.For more complicated diseases and complex treatments, envision a hybrid approach in which a patient comes in occasionally for an infusion and imaging on schedule, but receives much of the remainder of care and undergoes certain research procedures like blood sampling at home.Of course, there's a cost for this, and it isn't cheap.But if something like decentralized trials could double accrual and ensure compliance, it would be worth it for "big pharma."For them, "time is money," and completing trials quickly is important in drug development.This plan might also allow trials to be open in fewer sites, which is also a cost savings.Personally, I think this is the way to go, and it's great to know that the FDA is also on board.As for our patients, I think they'll love it.And that's what matters most.
Comparative Effectiveness of Single-Agent Ibrutinib in the Ray Trial Versus Real-World Treatment in the Lyon-Sud Database in Patients with Relapsed or Refractory Mantle Cell Lymphoma
Authors: Clementine Sarkozy, Alexandra Traverse-Glehen, Emmanuel Bachy, Lionel Karlin, Hervé Ghesquières, Hervé Besson, Ruben Hermans, Nollaig Healy, Jamie Garside, Joris Diels, Finlay MacDougall, Corinna Pick-Lauer, Gilles Salles
Journal: Blood (2017)
US drug pricing: Trump promises overhaul after judge blocks attempt to force cost disclosures
Authors: Owen Dyer
Journal: BMJ (2019)

A US federal judge has blocked a Trump administration rule that would have required drug manufacturers to display their list prices in all television drug advertisements. The rule, which was set to take effect later this week, would have been the first policy to actually be implemented in Trump’s drive to reduce prescription costs, which he has called a priority for his administration.

Judge Amit Mehta, of the US District Court in the District of Columbia, ruled on 8 July that the US Department of Health had exceeded its authority in making the rule.

The drug companies Merck, Eli Lilly, and Amgen, which sued together to block the rule, called it a violation of the first amendment. They also argued that many patients had health …
Analysis of Cell-Free DNA from 32,989 Advanced Cancers Reveals Novel Co-occurring Activating <i>RET</i> Alterations and Oncogenic Signaling Pathway Aberrations
Authors: Thereasa A. Rich, Karen L. Reckamp, Young Kwang Chae, Robert C. Doebele, Wade T. Iams, Michael Oh, Victoria M. Raymond, Richard B. Lanman, Jonathan W. Riess, Thomas E. Stinchcombe, Vivek Subbiah, David R. Trevarthen, Stephen Fairclough, Jennifer Yen, Oliver Gautschi
Journal: Clinical Cancer Research (2019)

Abstract Purpose: RET is an emerging oncogenic target showing promise in phase I/II clinical trials. An understudied aspect of RET-driven cancers is the extent to which co-occurring genomic alterations exist and how they may impact prognosis or therapeutic response. Experimental Design: Somatic activating RET alterations were identified among 32,989 consecutive patients with metastatic solid tumors tested with a clinical cell-free circulating tumor DNA (cfDNA) assay. This comprehensive next-generation sequencing (NGS) assay evaluates single-nucleotide variants, and select indels, fusions, and copy number gains in 68–73 clinically relevant cancer genes. Results: A total of 176 somatic activating RET alterations were detected in 170 patients (143 fusions and 33 missense mutations). Patients had non–small cell lung (NSCLC, n = 125), colorectal (n = 15), breast (n = 8), thyroid (n = 8), or other (n = 14) cancers. Alterations in other oncogenic signaling pathway genes were frequently identified in RET-positive samples and varied by specific RET fusion gene partner. RET fusions involving partners other than KIF5B were enriched for alterations in MAPK pathway genes and other bona fide oncogenic drivers of NSCLC, particularly EGFR. Molecular and clinical data revealed that these variants emerged later in the genomic evolution of the tumor as mechanisms of resistance to EGFR tyrosine kinase inhibitors. Conclusions: In the largest cancer cohort with somatic activating RET alterations, we describe novel co-occurrences of oncogenic signaling pathway aberrations. We find that KIF5B-RET fusions are highly specific for NSCLC. In our study, only non-KIF5B-RET fusions contributed to anti-EGFR therapy resistance. Knowledge of specific RET fusion gene partner may have clinical significance.
Dopamine Deficiency Reduces Striatal Cholinergic Interneuron Function in Models of Parkinson’s Disease
Authors: Jonathan W. McKinley, Ziqing Shi, Ivana Kawikova, Matthew Hur, Ian J. Bamford, Suma Priya Sudarsana Devi, Annie Vahedipour, Martin Darvas, Nigel S. Bamford
Journal: Neuron (2019)
Promoting Trust Between Patients and Physicians in the Era of Artificial Intelligence
Authors: Shantanu Nundy, Tara Montgomery, Robert M. Wachter
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Development and initial validation of the MS score for diagnosis of macrophage activation syndrome in systemic juvenile idiopathic arthritis
Authors: Francesca Minoia, Francesca Bovis, Sergio Davì, AnnaCarin Horne, Michel Fischbach, Michael Frosch, Adam Huber, Marija Jelusic, Sujata Sawhney, Deborah K McCurdy, Clóvis A Silva, Donato Rigante, Erbil Unsal, Nicolino Ruperto, Alberto Martini, Randy Q Cron, Angelo Ravelli
Journal: Annals of the Rheumatic Diseases (2019)

To develop and validate a diagnostic score that aids in identifying macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (sJIA).The clinical and laboratory features of 362 patients with sJIA-associated MAS and 404 patients with active sJIA without evidence of MAS were collected in a multinational collaborative project. Eighty percent of the study population was used to develop the score and the remaining 20% constituted the validation sample. A Bayesian Model Averaging approach was used to assess the role of each clinical and laboratory variables in the diagnosis of MAS and to obtain the coefficients of selected variables. The final score, named MAS/sJIA (MS) score, resulted from the linear combination of these coefficients multiplied by the values of each variable. The cut-off that best discriminated MAS from active sJIA was calculated by means of receiver operating characteristic (ROC) curve analysis. Score performance was evaluated in both developmental and validation samples.The MS score ranges from -8.4 to 41.8 and comprises seven variables: central nervous system dysfunction, haemorrhagic manifestations, active arthritis, platelet count, fibrinogen, lactate dehydrogenase and ferritin. A cut-off value ≥-2.1 revealed the best performance in discriminating MAS from active sJIA, with a sensitivity of 0.85, a specificity of 0.95 and a kappa value of 0.80. The good performance of the MS score was confirmed in the validation sample.The MS score is a powerful and feasible tool that may assist practitioners in making a timely diagnosis of MAS in patients with sJIA.
Consensus criteria for diagnosis, staging, and treatment response assessment of T-cell prolymphocytic leukemia
Authors: Philipp B. Staber, Marco Herling, Mar Bellido, Eric D. Jacobsen, Matthew S. Davids, Tapan Mahendra Kadia, Andrei Shustov, Olivier Tournilhac, Emmanuel Bachy, Francesco Zaja, Kimmo Porkka, Gregor Hoermann, Ingrid Simonitsch-Klupp, Claudia Haferlach, Stefan Kubicek, Marius E. Mayerhoefer, Georg Hopfinger, Ulrich Jaeger, Claire Dearden
Journal: Blood (2019)
Distinct Patterns of Daily Glucose Variability by Pubertal Status in Youth With Type 1 Diabetes
Authors: Jia Zhu, Lisa K. Volkening, Lori M. Laffel
Journal: Diabetes Care (2019)

OBJECTIVE To evaluate glycemia and metrics of glucose variability in youth with type 1 diabetes, and to assess patterns of 24-h glucose variability according to pubertal status. RESEARCH DESIGN AND METHODS Metrics of glycemia, glucose variability, and glucose patterns were assessed by using 4 weeks of continuous glucose monitoring (CGM) data from 107 youth aged 8–17 years with type 1 diabetes for ≥1 year. Glucose values per hour were expressed as percentages relative to the mean glucose over 24 h for a 4-week period. Glucose data were compared on the basis of pubertal status—prepubertal (Tanner stage [T] 1), pubertal (T2–4), and postpubertal (T5)—and A1C categories (&amp;lt;7.5% [&amp;lt;58 mmol/mol], ≥7.5% [≥58 mmol/mol]). RESULTS Youth (50% female, 95% white) had a mean ± SD age of 13.1 ± 2.6 years, diabetes duration of 6.3 ± 3.5 years, and A1C of 7.8 ± 0.8% (62 ± 9 mmol/mol); 88% were pump treated. Prepubertal youth had a higher mean glucose SD (86 ± 12 mg/dL [4.8 ± 0.7 mmol/L]; P = 0.01) and coefficient of variation (CV) (43 ± 5%; P = 0.06) than did pubertal (SD 79 ± 13 mg/dL [4.4 ± 0.7 mmol/L]; CV 41 ± 5%) and postpubertal (SD 77 ± 14 mg/dL [4.3 ± 0.8 mmol/L]; CV 40 ± 5%) youth. Over 24 h, prepubertal youth had the largest excursions from mean glucose and the highest CV across most hours compared with pubertal and postpubertal youth. Across all youth, CV was strongly correlated with the percentage of time with glucose &amp;lt;70 mg/dL (&amp;lt;3.9 mmol/L) (r = 0.79; P &amp;lt; 0.0001). CONCLUSIONS Prepubertal youth had greater glucose variability independent of A1C than did pubertal and postpubertal youth. A1C alone does not capture the full range of glycemic parameters, highlighting the added insight of CGM in managing youth with type 1 diabetes.
Author Correction: Farm-like indoor microbiota in non-farm homes protects children from asthma development
Authors: Pirkka V. Kirjavainen, Anne M. Karvonen, Rachel I. Adams, Martin Täubel, Marjut Roponen, Pauli Tuoresmäki, Georg Loss, Balamuralikrishna Jayaprakash, Martin Depner, Markus Johannes Ege, Harald Renz, Petra Ina Pfefferle, Bianca Schaub, Roger Lauener, Anne Hyvärinen, Rob Knight, Dick J. J. Heederik, Erika von Mutius, Juha Pekkanen
Journal: Nature Medicine (2019)
Psychosocial distress and access to resources: Preliminary findings from <i>Immunotherapy &amp; Me</i>.
Authors: Maxwell Mulcahy, Linda S. House, Nicholas James Power, Julie Olson, Shauna McManus, Tameka N. Jones, Lee S. Schwartzberg
Journal: Journal of Clinical Oncology (2019)

91 Background: Immunotherapy &amp; Me ( IO &amp; Me) is an innovative program of supportive resources developed by Cancer Support Community to investigate and support the unique needs of immunotherapy patients. Here, we describe psychosocial distress and confidence accessing resources among a sample of program participants. Methods: IO &amp; Me is recruiting at 4 community clinics and 1 academic center. Eligible patients must be on an anti-cancer immunotherapy. At enrollment, participants consent, provide demographic/clinical history, and report level of confidence accessing cancer treatment information and resources related to treatment decision making (TDM) and managing symptoms/side effects (SEs). Distress is reported with CancerSupportSource (CSS), a tool where patients rate level of concern on 15 items. Once enrolled, participants can access educational resources (print materials, SE tracker, eLearning courses) and a toll-free helpline staffed by licensed mental health professionals (Cancer Support Helpline). Follow-up surveys are available every 30 days for 6 months. We present data from 68 participants at enrollment and 22 at first follow-up. Results: Participants were 87% White; 69% male; mean age = 65 years (SD = 13). 43% had lung cancer; 22% melanoma; 9% kidney cancer. At baseline, the frequency who felt very or extremely confident accessing resources related to: TDM = 68%; managing SEs = 60%; treatment information = 75%. For distress, top concerns were: fatigue (35% of participants); health insurance/money worries (34%); exercise/physical activity (32%). After 30 days, the frequency who felt confident accessing resources for: TDM = 100%; managing SEs = 91%; treatment information = 100%. Top concerns were: changes/disruptions in work, school, or home life (14%); feeling irritable (9%); sleep problems (9%). Conclusions: Preliminary results show greater variability in distress and confidence accessing resources at baseline than 1-month into the program, at which time few endorse cancer-related concerns and most feel confident accessing resources. These findings highlight the utility of providing patients with educational/support resources and the value of customizable programs like IO &amp; Me. Clinical trial information: NCT03347058.
Selection of unrelated donors and cord blood units for hematopoietic cell transplantation: guidelines from the NMDP/CIBMTR
Authors: Jason Dehn, Stephen Spellman, Carolyn K. Hurley, Bronwen E. Shaw, Juliet N. Barker, Linda J. Burns, Dennis L. Confer, Mary Eapen, Marcelo Fernandez-Vina, Robert Hartzman, Martin Maiers, Susana R. Marino, Carlheinz Mueller, Miguel-Angel Perales, Raja Rajalingam, Joseph Pidala
Journal: Blood (2019)
From functional genomics to precision medicine: The therapeutic potential of targeting ROCK signaling in pancreatic cancer.
Authors: Venessa T. Chin, Adnan Nagrial, Lorraine A. Chantrill, David K. Chang, Angela Chou, Jeremy Humprhis, Mark Cowley, Jiamin Wu, Renee DiPetro, Clare Watson, Calan Spielman, Angela Steinmann, Mark Pinese, Jessica Pettitt, Amber Johns, Nicola Waddell, Sean Grimmond, Paul Timpson, Andrew Victor Biankin, Marina Pajic
Journal: Journal of Clinical Oncology (2013)

e15029 Background: Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options for metastatic disease. PC is a genetically highly heterogeneous disease that lends itself to a personalised approach to translational research (Biankin et al. Nature. 2012 Nov 15;491(7424):399-405.). Genomic sequence data from the Australian Pancreatic Genome Initiative (APGI) has identified a subset of patients with ROCK-1 amplification. ROCK-1 is a downstream target of Rho, a small GTPase, which is involved in cell adhesion and motility and has been shown to play a role in cancer cell growth and invasiveness (S. Boeck, P. Stieber, et al. Oncology 2006; 70:255., Lane J, Martin T et al. Int J Onc 2008; 33:585-593.). Our aim is to identify biologically and clinically relevant, targetable phenotypes for PC by examining therapeutic efficacy of two ROCK-1 inhibitors, Y-27632 and fasudil in model systems with aberrant Rho/ROCK signaling. Methods: Using extensively characterised model systems of PC, including unique primary patient derived xenografts (PDX) and patient derived cell lines (PDCL) established in the laboratory, we are examining the efficacy of individualized rationally designed combination therapies based on targeting Rho/ROCK signaling. Using innovative techniques, including organotypic assays, we are examining the effect of the targeted approach on cell proliferation, migration, invasion and metastasis in relevant models of PC. Results: Here we demonstrate significant differential sensitivity of pancreatic PDXs and PDCLs with aberrant Rho/ROCK signaling to ROCK combination therapy when compared with standard therapy, gemcitabine. Finally, these compounds impair invasiveness of human pancreatic tumour cells, suggesting that ROCK-1 is a targetable phenotype for the treatment of PC. Conclusions: By carefully defining the key cancer subtypes and expanding our knowledge about the interplay of the key regulators and activators of the Rho/ROCK pathway, the promise of ROCK inhibitors for PC therapy may be realized. As fasudil is already in clinical use for the treatment of cerebral vasospasm, this work may be quickly translated to the clinic.