tbuckley/cabot-search huggingface dataset:
Safety and feasibility of outpatient high-dose cytarabine (HIDAC) and intermediate-dose cytarabine (IDAC) for consolidation therapy in acute myeloid leukemia (AML).
Authors: Wenhui Li, Katherine Simondsen, Jamie Lee, Maher Elharake, Timothy Edward Kubal
Journal: Journal of Clinical Oncology (2019)

e18509 Background: Patients with acute myeloid leukemia (AML) who achieve complete remission with induction therapy require consolidation therapy. The standard of care consolidation is HIDAC or IDAC depending on age and risk stratification. Consolidation therapy has historically been administered in the inpatient setting. The rising cost of AML care has prompted institutions to consider shifting therapy to the outpatient setting. However, the safety and feasibility of outpatient HIDAC/IDAC consolidation therapy has not been established. Moffitt Cancer Center (MCC) developed an Inpatient/Outpatient (IPOP) program to facilitate administration of complicated regimens in the outpatient setting. We hypothesized that IPOP administration of HIDAC/IDAC consolidation therapy is safe and may have cost-savings implications. Methods: We conducted a retrospective chart review on AML patients who were 18 years or older and received HIDAC/IDAC consolidation therapy at MCC following induction therapy from January 1, 2015 to November 1, 2018. Data collected included age, risk stratification, treatment history, clinic visits, number of cycles received in the IPOP versus inpatient setting, supportive care, hospitalizations, and chemotherapy related adverse events. Results: 258 of 270 cycles of HIDAC/IDAC were delivered outpatient over the reviewed time period to 122 patients. 45 patients (37%) required hospitalization during consolidation with the primary reason being neutropenic fever (72%), consistent with historical data (50 to 90%). No patients receiving outpatient consolidation required hospitalization during chemotherapy. Specific details regarding administration of HIDAC/IDAC in IPOP, including infusion times, frequency of visits, laboratory frequency, supportive medications, and home antimicrobials will be reported. 1,290 hospital days were saved through IPOP administration. Financial assessment of cost-savings is being determined and will be reported. Conclusions: Outpatient administration of HIDAC/IDAC consolidation therapy for AML is a safe option for AML patients undergoing consolidation.
BRCA1 and MGMT gene promoter methylation predicts for chemoresponsiveness in epithelial ovarian cancer [EOC]
Authors: Radhika Srinivasan, Parvesh Chaudhry, Firuza Patel, Sarala Gopalan
Journal: Cancer Research (2007)

1047    BACKGROUND:  Ovarian cancer is the second most common and most fatal of the gynaecological malignancies. Platinum-based combination chemotherapy is the mainstay of treatment of ovarian cancer. These agents act by inducing DNA damage and apoptosis and so genes regulating these processes such as  BRCA1, MGMT, MLH1, RASSF1A  may be involved in determining tumor chemoresponsiveness. CpG island methylation of gene promoters is frequently altered in cancer and has been implicated in response to chemotherapy.  OBJECTIVE:  To determine the methylation status of  BRCA1, MGMT, MLH1, RASSF1A  and  p16  genes and to correlate the methylator phenotypes to chemoresponsiveness as determined clinically.  METHODS:  Thirty-five women with FIGO stage III epithelial ovarian cancer underwent surgical cytoreduction followed by platinum-based chemotherapy regimen. After an informed consent, a portion of the tumor was snap frozen for molecular analysis.The methylation-specific polymerase chain reaction (MS-PCR) technique was employed to assay the methylation status of the gene promoters. The response to platinum-based chemotherapy was documented clinically, radiologically and by serial CA-125 levels. At the end of 6 cycles of chemotherapy, based on their initial response, two groups were identified: Primary chemosensitive (PCs, n=24) and primary chemoresistant (PCr, n=11). The patients were further followed up [9-33 mo], on the basis of which, two groups were identified: No Evidence of Disease (NED, n=15) and Evidence of disease [ED (Stable/Progressive Disease), n=20]. Statistical analysis was performed on these groups by the Pearson’s Chi-square test.  RESULTS:  Frequent methylation was observed for  BRCA1  (48%) and  RASSF1A  (37%) genes. Methylation frequency of  p16, MGMT and MLH1  were 25%, 20% and 5% respectively. Methylated  BRCA1  (p MGMT  (p=0.05) showed a significant correlation to primary chemosensitivity. Further, methylated  BRCA1  (p=0.05) and  p16  (p=0.03) predicted for No Evidence of Disease at a mean follow-up period of 18months [Range 9-33 mo].Methylation of at least one of the group of genes involved in DNA repair/cell cycle (BRCA1, MGMT and p16) was associated with improved response to chemotherapy (p = 0.002).  CONCLUSION:  In EOC, methylation profiling of a limited number of genes involved in DNA repair such as  BRCA1  and  MGMT  is useful in prediction of response to chemotherapy. This is particularly applicable in a low-resource setting where high-throughput approaches are not available.  BRCA1  and  p16  gene methylation status are also promising prognostic markers.
Abstract 16863: Cardiac Magnetic Resonance T1 Mapping as a Window Into the Myocardium in Friedreich Ataxia
Authors: Kimberly Y Lin, Martin Delatycki, Louise Corben, Michael Cheung, Victor Ferrari, Mark Fogel, Stuart Moir, Roger Peverill
Journal: Circulation (2018)

Introduction: Left ventricular (LV) remodeling and hypertrophy are common findings in Friedreich Ataxia (FA) and associated with a poorer prognosis. Cardiac magnetic resonance (CMR) T1 mapping, a technique used to assess myocardial fibrosis, may be able to identify cardiomyopathic changes in FA at an early stage of the cardiac disease process. We hypothesized that T1 mapping variables would demonstrate myocardial involvement in FA independently of the recognized LV structural and functional changes. Methods: A standardized CMR protocol including T1 mapping and measurements of LV mass, LV end-diastolic volume, native T1 time, post gadolinium (PostGad) T1 time, and calculation of the LV mass/volume ratio (LVMVR), partition coefficient (PC), and extracellular volume (ECV) was performed at two sites on FA subjects who were homozygous for GAA repeats in the FXN gene. GAA repeat length in the shorter allele (GAA1) of the frataxin gene ( FXN ) was used as a surrogate for the degree of frataxin deficiency. Results: Ninety-five FA subjects (56% males, median age 22 yrs, age of onset 10 yrs, GAA1 700) were scanned. Nine FA subjects had a LV ejection fraction (EF) &amp;lt;55%; their T1 variables were not different than those with preserved LVEF. Fifty-three subjects had an elevated LVMVR (&amp;gt;1.20); their T1 variables were not different from those without an elevated LVMVR. On multivariate analysis, GAA1 correlated with native T1 time (p=0.009), PostGad T1 time (p=0.003), PC (p&amp;lt;0.001), and ECV (p&amp;lt;0.001) after adjusting for sex, age and site. LVMVR was a correlate of native T1 time when adjusted for sex, age and site (p=0.019), but not when also adjusted for GAA1, whereas GAA1 still predicted native T1 when adjusted for sex, age, site, and LVMVR (p=0.018). Conclusion: T1 mapping provides information about the myocardium in FA which is correlated with the degree of frataxin deficiency and is independent of LV remodeling. Study of the relationship between T1 variables and cardiac outcomes is now needed to help determine the utility of this technique as a monitoring and prognostic biomarker for this rare disease.
Prevalence, severity, and nature of preventable patient harm across medical care settings: systematic review and meta-analysis
Authors: Maria Panagioti, Kanza Khan, Richard N Keers, Aseel Abuzour, Denham Phipps, Evangelos Kontopantelis, Peter Bower, Stephen Campbell, Razaan Haneef, Anthony J Avery, Darren M Ashcroft
Journal: BMJ (2019)

Abstract Objective To systematically quantify the prevalence, severity, and nature of preventable patient harm across a range of medical settings globally. Design Systematic review and meta-analysis. Data sources Medline, PubMed, PsycINFO, Cinahl and Embase, WHOLIS, Google Scholar, and SIGLE from January 2000 to January 2019. The reference lists of eligible studies and other relevant systematic reviews were also searched. Review methods Observational studies reporting preventable patient harm in medical care. The core outcomes were the prevalence, severity, and types of preventable patient harm reported as percentages and their 95% confidence intervals. Data extraction and critical appraisal were undertaken by two reviewers working independently. Random effects meta-analysis was employed followed by univariable and multivariable meta regression. Heterogeneity was quantified by using the I 2 statistic, and publication bias was evaluated. Results Of the 7313 records identified, 70 studies involving 337 025 patients were included in the meta-analysis. The pooled prevalence for preventable patient harm was 6% (95% confidence interval 5% to 7%). A pooled proportion of 12% (9% to 15%) of preventable patient harm was severe or led to death. Incidents related to drugs (25%, 95% confidence interval 16% to 34%) and other treatments (24%, 21% to 30%) accounted for the largest proportion of preventable patient harm. Compared with general hospitals (where most evidence originated), preventable patient harm was more prevalent in advanced specialties (intensive care or surgery; regression coefficient b=0.07, 95% confidence interval 0.04 to 0.10). Conclusions Around one in 20 patients are exposed to preventable harm in medical care. Although a focus on preventable patient harm has been encouraged by the international patient safety policy agenda, there are limited quality improvement practices specifically targeting incidents of preventable patient harm rather than overall patient harm (preventable and non-preventable). Developing and implementing evidence-based mitigation strategies specifically targeting preventable patient harm could lead to major service quality improvements in medical care which could also be more cost effective.
On the potential distortions of highly cited papers in emerging research fields: A critical appraisal
Authors: Edoardo G. Ostinelli, Orsola Gambini, Armando D'Agostino
Journal: Behavioral and Brain Sciences (2019)

Abstract Citation-based metrics are increasingly used as a proxy to define representative, considerable, or significant papers. We challenge this belief by taking into account factors that may play a role in providing citations to a manuscript and whether/how those highly cited studies could shape a scientific field. A different approach to summarisation of relevant core publications within a topic is proposed.
Controlled attenuation parameter does not predict hepatic decompensation in patients with advanced chronic liver disease
Authors: B. Scheiner, L. Steininger, G. Semmler, P. Schwabl, T. Bucsics, R. Paternostro, A. Ferlitsch, M. Trauner, T. Reiberger, M. Mandorfer
Journal: Journal of Hepatology (2018)
Abstract 14039: Antiarrhythmic Drug Use and Success Rates After Catheter Ablation for Atrial Fibrillation: Findings From the SMASH-AF Meta-Analysis Study Cohort
Authors: Andrew Cluckey, Fahd N Yunus, George C Leef, Mariam Askari, Paul Heidenreich, Mintu P Turakhia, Alexander C Perino
Journal: Circulation (2017)

Introduction: Atrial fibrillation (AF) ablation has been shown superior to antiarrhythmic drugs (AAD) for maintenance of sinus rhythm. However, there has been limited investigation into the magnitu...
Variations in Surgical Safety According to Affiliation Status With a Top-Ranked Cancer Hospital
Authors: Benjamin J. Resio, Jessica R. Hoag, Alexander S. Chiu, Andres Monsalve, Tejas Sathe, Xiao Xu, Daniel J. Boffa
Journal: JAMA Oncology (2019)

It is recognized that evaluation of OS can be challenging or unfeasible in some instances and is complicated by factors such as use of crossover trial design.Where possible, the requirement for postmarketing studies confirming an OS benefit, enforcement of timely completion of the studies, and action should those studies fail to show a benefit represents one avenue by which the FDA could improve the number of oncology drugs that provide true meaningful benefits to patients.
Investigating a 7-day baseline while establishing healthy scat3 symptom frequency and severity
Authors: Michael Robinson, Danielle Mc Elhiney
Journal: British Journal of Sports Medicine (2017)

Objective The reliability of a concussion symptom checklist can become compromised by external conditions (weather, medical conditions, stress, medications, etc.). This study assessed the day-to-day reliability of the SCAT3 Symptom Evaluation to determine if participants provide consistent responses in addition to determining the frequency and severity of the 22 symptoms in a non-concussed, adult, athletic population. Design Repeated measure observational design. Setting This study was conducted at a University in Ohio, U.S.A. Participants 52 volunteers (18 to 30 years), self-identified as an athlete and had not suffered a concussion in the past 6 months. Intervention Participants completed the SCAT3 Symptom Evaluation at prescribed times through the day over a 7 day period. Participants were randomly assigned to two equal groups, alternating between completing the SCAT3 Symptom Evaluation twice (at wake up and before bed) or once (in the afternoon) each day. Outcome measures Severity and frequency of each of the 22 symptoms over a 7 day period. Main results The single measure intraclass correlation coefficient was 0.496 (95% CI=0.382 to 0.620, SEM=0.134) for the frequency of symptoms and 0.438 (95% CI=0.325 to 0.568, SEM=0.221) for the sum of the symptom severity over 7 days. Conclusions The results demonstrated poor day-to-day reliability for the reporting of the frequency and severity of symptoms. All of the 22 symptoms on the SCAT3 Symptom Checklist were reported by at least one participant with the most commonly reported symptoms being fatigue or low energy, drowsiness, and headaches. Competing interests None.
International prevalence and risk factors evaluation for drug-resistant Streptococcus pneumoniae pneumonia
Authors: Stefano Aliberti, Grayden S. Cook, Bettina L. Babu, Luis F. Reyes, Alejandro H. Rodriguez, Francisco Sanz, Nilam J. Soni, Antonio Anzueto, Paola Faverio, Ricardo Franco Sadud, Irfan Muhammad, Cristina Prat, Ester Vendrell, Joao Neves, Evangelos Kaimakamis, Andrew Feneley, Rajesh Swarnakar, Fabio Franzetti, Manuela Carugati, Manuela Morosi, Elisa Monge, Marcos I. Restrepo
Journal: Journal of Infection (2019)
A randomized trial comparing four-weekly versus 12-weekly administration of bone-targeted agents (denosumab, zoledronate, or pamidronate) in patients with bone metastases from either breast or castration-resistant prostate cancer.
Authors: Mark J. Clemons, Michael Ong, Carol Stober, D. Scott Ernst, Christopher M. Booth, Christina M. Canil, Mihaela Mates, Andrew George Robinson, Phillip S. Blanchette, Anil Abraham Joy, John Frederick Hilton, Olexiy Aseyev, Gregory Russell Pond, Brian Hutton, Ahwon Jeong, Lisa Vandermeer, Dean Fergusson
Journal: Journal of Clinical Oncology (2019)

11501 Background: Defining the optimal dosing interval of commonly used bone-targeted agents (BTAs), such as denosumab and bisphosphonates, for patients with bone metastases remains an important clinical question. We performed a pragmatic randomised trial comparing the non-inferiority of 12- versus 4-weekly BTAs in patients with bone metastases from breast and prostate cancer. Methods: Patients with bone metastases, who were either BTA-naïve, or already receiving, denosumab, pamidronate or zoledronate were eligible. They were randomised to receive their chosen BTA every 12- or 4-weeks for one year. The primary endpoint was Health related quality of life (HRQL) (EORTC-QLQ-C30 Functional Domain - Physical Subdomain). Secondary endpoints included: pain (EORTC-QLQ-BM22 - pain domain), Global Health Status (EORTC-QLQ-C30), symptomatic skeletal events (SSE) rates and time to SSEs. Adverse events and toxicity profiles were also compared. Results: Of 263 patients (60.8% breast and 39.2% prostate), 130 (49.4%) were randomised to 12-weekly and 133 (50.6%) to 4-weekly therapy. 138 (52.5%) were bone-agent naïve. The BTAs included; denosumab (n=148, 56.3%), zoledronate (n=63, 24.0%) and pamidronate (n=52, 19.8%). Study-reported outcomes showed no significant difference in; HRQL-physical domain (median [range]: 0 [-86, 40] vs. 0 [-66, 53.3]), pain (median [range]: 0 [-66, 72] vs. 0 [-100, 88]), Global Health Status (median [range]: 0 [-100, 66.7] vs. 0 [-83, 33.3]), SSE rates (N [%]: 24 [18.5%] vs. 22 [16.5%]), 1-year SSE-free rate (median, range; 73.2% [63.6, 80.7] vs. 77.9% [69.1, 84.4]) between the 12- and 4-weekly arms, respectively. Subgroup analyses for BTA naïve and pre-treated patients, and for patients receiving denosumab, zoledronate and pamidronate, showed no significant difference between the 12- and 4-weekly arms. There was no significant difference in reported rates of renal impairment (2.3% vs. 3.0%), symptomatic hypocalcaemia (1.5% vs. 1.5%) or osteonecrosis of the jaw (0.8% vs. 0.8%). Conclusion: The findings of this trial are consistent with those previously reported for de-escalating zoledronate. This trial also included patients receiving de-escalated denosumab and pamidronate. While the results of the Swiss REDUSE trial are awaited, the data presented would suggest that de-escalation of all commonly used BTAs is a reasonable treatment option. Clinical trial information: NCT02721433.
Short-term complications and use of breast brachytherapy in the national Medicare population in 2008-2009.
Authors: Carolyn J. Presley, Pamela R. Soulos, Jeph Herrin, Kenneth B Roberts, James B. Yu, Brigid K. Killelea, Beth-Ann Lesnikoski, Jessica B. Long, Cary P. Gross
Journal: Journal of Clinical Oncology (2012)

1030 Background: Brachytherapy as an alternative to whole-breast irradiation (WBI) for early-stage breast cancer has disseminated into clinical practice; however, current national treatment patterns and associated complications remain unknown. Methods: We constructed a national sample of Medicare beneficiares aged 66 to 94 who underwent breast conserving surgery in 2008-2009 and who were treated with brachytherapy or WBI. We used hospital referral regions to assess national treatment variation and an instrumental variable analysis to compare complication rates between treatment groups, adjusting for patient and clinical characteristics such as age, number of comorbidities, receipt of chemotherapy or screening mammogram, and type of radiation facility. We compared one-year overall, wound and skin, and deep tissue and bone complications between brachytherapy and WBI using specific procedure and diagnosis codes identified in Medicare claims. Results: Of the 29,648 women in our sample, 4,671 (15.8%) received brachytherapy. The median percent of patients receiving brachytherapy varied substantially across hospital referral regions (interquartile range: 7.5%-23.3%). In the bivariate analysis, 34.3% of women treated with brachytherapy had a complication compared to 27.3% of those who received WBI (P&lt;0.001). After adjusting for patient and clinical characteristics, 35.3% (95% CI: 34.7, 35.8) of women treated with brachytherapy had a complication compared to 18.7% (95% CI: 18.2,19.2) treated with WBI (average predicted difference: 16.5%, 95% CI: 15.8, 17.3, P&lt;0.001). While brachytherapy was associated with a 16.9% (95% CI: 10.0, 23.8, P&lt;0.001) higher absolute percentage of wound and skin complications compared to WBI, there was no difference in deep tissue and bone complications. Conclusions: Brachytherapy is commonly used among Medicare beneficiaries; in some regions nearly one in four women who underwent adjuvant radiation received brachytherapy. After one year, wound and skin complications were significantly more common among women who received brachytherapy compared to those receiving WBI, but there was no difference in deep tissue and bone complications.
Educational and Health Outcomes of Children Treated for Type 1 Diabetes: Scotland-Wide Record Linkage Study of 766,047 Children
Authors: Michael Fleming, Catherine A. Fitton, Markus F.C. Steiner, James S. McLay, David Clark, Albert King, Robert S. Lindsay, Daniel F. Mackay, Jill P. Pell
Journal: Diabetes Care (2019)

OBJECTIVE This study was conducted to determine the association between childhood type 1 diabetes and educational and health outcomes. RESEARCH DESIGN AND METHODS Record linkage of nine Scotland-wide databases (diabetes register, dispensed prescriptions, maternity records, hospital admissions, death certificates, annual pupil census, school absences/exclusions, school examinations, and unemployment) produced a cohort of 766,047 singleton children born in Scotland who attended Scottish schools between 2009 and 2013. We compared the health and education outcomes of schoolchildren receiving insulin with their peers, adjusting for potential confounders. RESULTS The 3,330 children (0.47%) treated for type 1 diabetes were more likely to be admitted to the hospital (adjusted hazard ratio [HR] 3.97, 95% CI 3.79–4.16), die (adjusted HR 3.84, 95% CI 1.98–7.43), be absent from school (adjusted incidence rate ratio [IRR] 1.34, 95% CI 1.30–1.39), and have learning difficulties (adjusted odds ratio [OR] 1.19, 95% CI 1.03–1.38). Among children with type 1 diabetes, higher mean HbA1c (particularly HbA1c in the highest quintile) was associated with greater absenteeism (adjusted IRR 1.75, 95% CI 1.56–1.96), increased school exclusion (adjusted IRR 2.82, 95% CI 1.14–6.98), poorer attainment (adjusted OR 3.52, 95% CI 1.72–7.18), and higher risk of unemployment (adjusted OR 2.01, 95% CI 1.05–3.85). CONCLUSIONS Children with type 1 diabetes fare worse than their peers in respect of education and health outcomes, especially if they have higher mean HbA1c. Interventions are required to minimize school absence and ensure that it does not affect educational attainment.
Inhibition of natriuretic peptide receptor 1 reduces itch in mice
Authors: Hans Jürgen Solinski, Patricia Dranchak, Erin Oliphant, Xinglong Gu, Thomas W. Earnest, John Braisted, James Inglese, Mark A. Hoon
Journal: Science Translational Medicine (2019)

Natriuretic peptide receptor 1 inhibition with small molecules has therapeutic effects in mouse models of acute and chronic itch.