tbuckley/cabot-search huggingface dataset:
Concomitant chemoradiation versus radiotherapy in advanced squamous cell carcinoma of oropharynx and nasopharynx using weekly cisplatin: Final result of a phase III trial
Authors: A. Sharma, B. K. Mohanti, A. Thakar, S. Bahadur, S. Bhasker, A. Bahl
Journal: Journal of Clinical Oncology (2007)

6030 Background: Studies have confirmed the role of concomitant chemoradiation (CTRT) in the treatment of advanced SCCHN, however, there is no large study reported from India. Consensus about type and schedule of the chemotherapy is unclear e.g. single agent Vs combination; daily/weekly/three weekly. This study was undertaken to know effectiveness of weekly Cisplatin (DDP). Methods: prospective randomized phase III study. 153 untreated stage II-IV oropharyngeal and nasopharyngeal cancer patients were randomly assigned to one of the two treatment arm; Arm (A) Radical radiotherapy 70 Gy/ 35# over 7 weeks; Arm (B) CTRT; Cisplatin 40mg/m 2 weekly for 6 doses beginning day 1 of radiation treatment plus radiotherapy as in arm (A). The objective endpoints were- to know (i) the responses, (ii) toxicity profile and (iii) overall survival in the two treatment groups. Protocol was approved by local ethics committee. Study period was from June 2003 to July 2005. Results: Number of patients were 76 (A) and 77 (B) in two arms respectively. CR was 70.7 Vs 78.9% in arm A and B. Toxicity- grade III and IV toxicities were 16% and 40% respectively in 2 arms (p=&lt;0.05). There were more frequent interruptions (9.3% Vs 28.9%) and hospitalization (20% Vs 40.8%) (p=&lt;0.05) in CTRT arm. Survival- with median follow up of 17 months overall survival was significantly higher in CTRT arm (p=0.024); 27 months (95%CI 15.2–36.8) for RT Vs not reached (NR) for CTRT group. Three year OS was 42% Vs 62% respectively. Conclusion: This trial confirms that CTRT using single agent weekly DDP is safe and superior to RT in advanced SCCHN but treatment interruptions and toxicities are of concern for developing country’s cancer care infrastructures. No significant financial relationships to disclose. [Table: see text]
Characterization of published errors in high-impact oncology journals
Authors: A. Molckovsky, M. M. Vickers, P. A. Tang
Journal: Journal of Clinical Oncology (2009)

6627 Background: Knowledge within oncology is disseminated primarily via peer-reviewed journals. The potential for dissemination of erroneous data exists, an issue that has not been explored in oncology. We evaluated errata from the Journal of Clinical Oncology and the Journal of the National Cancer Institute published between 2004–2007. Methods: Two authors independently abstracted data regarding errata and classified them as trivial (eg typographical error) or serious (eg change in outcome). For serious errors, the frequency of citation and error propagation was determined using the Science Citation Index in Web of Science. For publications cited &gt; 150 times, a random sample of 10% were evaluated for error propagation. Canadian oncologists were surveyed regarding attitudes towards published errata. Results: There were 190 published errors, out of a total of 5118 papers, for an error rate of 4 ± 1% (SD) per year. 26/190 errors were identified as serious (14%). The median time from publication of the original article to publication of the erratum was 3.5 mo for trivial errors compared to 8.3 mo for serious errors (p = 0.03). A median of 1 error per article was reported for papers with trivial errors compared to a median of 2 errors per article with serious errors (p &lt; 0.01). The 26 articles with serious errors were cited 256 times before publication of the error and 1056 times afterwards; of these, 96 and 527, respectively, were evaluated for propagation. Error propagation occurred in 14.6% of the citations published before error publication, and in 3.4% of citations published afterwards (p &lt; 0.001). Survey results indicate that 30% of oncologists do not read the erratum section of journals, and that 45% of oncologists have only read the abstract of an article before citing it in a publication. Although 58% of oncologists have noticed errors in cancer publications, only 15% of these errors were reported. Conclusions: Error rates in high impact oncology journals average 4% per year, but this is likely an underestimate since errors noticed by readers are not consistently reported to the journal. The accuracy of articles submitted for publication is of utmost importance; while error propagation decreases after erratum publication, serious errors continue to be propagated in the literature. No significant financial relationships to disclose.
Variation in responsiveness to warranted behaviour change among NHS clinicians: novel implementation of change detection methods in longitudinal prescribing data
Authors: Alex J Walker, Felix Pretis, Anna Powell-Smith, Ben Goldacre
Journal: BMJ (2019)

To determine how clinicians vary in their response to new guidance on existing or new interventions, by measuring the timing and magnitude of change at healthcare institutions.Automated change detection in longitudinal prescribing data.Prescribing data in English primary care.English general practices.In each practice the following were measured: the timing of the largest changes, steepness of the change slope (change in proportion per month), and magnitude of the change for two example time series (expiry of the Cerazette patent in 2012, leading to cheaper generic desogestrel alternatives becoming available; and a change in antibiotic prescribing guidelines after 2014, favouring nitrofurantoin over trimethoprim for uncomplicated urinary tract infection (UTI)).Substantial heterogeneity was found between institutions in both timing and steepness of change. The range of time delay before a change was implemented was large (interquartile range 2-14 months (median 8) for Cerazette, and 5-29 months (18) for UTI). Substantial heterogeneity was also seen in slope following a detected change (interquartile range 2-28% absolute reduction per month (median 9%) for Cerazette, and 1-8% (2%) for UTI). When changes were implemented, the magnitude of change showed substantially less heterogeneity (interquartile range 44-85% (median 66%) for Cerazette and 28-47% (38%) for UTI).Substantial variation was observed in the speed with which individual NHS general practices responded to warranted changes in clinical practice. Changes in prescribing behaviour were detected automatically and robustly. Detection of structural breaks using indicator saturation methods opens up new opportunities to improve patient care through audit and feedback by moving away from cross sectional analyses, and automatically identifying institutions that respond rapidly, or slowly, to warranted changes in clinical practice.
Artificial Intelligence in Drug Treatment
Authors: Eden L. Romm, Igor F. Tsigelny
Journal: The Annual Review of Pharmacology and Toxicology (2019)

The most common applications of artificial intelligence (AI) in drug treatment have to do with matching patients to their optimal drug or combination of drugs, predicting drug-target or drug-drug interactions, and optimizing treatment protocols. This review outlines some of the recently developed AI methods aiding the drug treatment and administration process. Selection of the best drug(s) for a patient typically requires the integration of patient data, such as genetics or proteomics, with drug data, like compound chemical descriptors, to score the therapeutic efficacy of drugs. The prediction of drug interactions often relies on similarity metrics, assuming that drugs with similar structures or targets will have comparable behavior or may interfere with each other. Optimizing the dosage schedule for administration of drugs is performed using mathematical models to interpret pharmacokinetic and pharmacodynamic data. The recently developed and powerful models for each of these tasks are addressed, explained, and analyzed here.
Preoperative Circulating Succinate Levels as a Biomarker for Diabetes Remission After Bariatric Surgery
Authors: Victoria Ceperuelo-Mallafré, Gemma Llauradó, Noelia Keiran, Ester Benaiges, Brenno Astiarraga, Laia Martínez, Silvia Pellitero, Jose Miguel González-Clemente, Amaia Rodríguez, José Manuel Fernández-Real, Albert Lecube, Ana Megía, Nuria Vilarrasa, Joan Vendrell, Sonia Fernández-Veledo
Journal: Diabetes Care (2019)

OBJECTIVE To determine the potential use of baseline circulating succinate to predict type 2 diabetes remission after bariatric surgery. RESEARCH DESIGN AND METHODS Forty-five obese patients with diabetes were randomly assigned to Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or laparoscopic greater curvature plication. Anthropometric parameters were evaluated, and a complete biochemical analysis including circulating serum succinate concentrations was performed at baseline and 1 year after surgery. The results were externally validated in a second cohort including 88 obese patients with diabetes assigned to RYGB or SG based on clinical criteria. RESULTS Succinate baseline concentrations were an independent predictor of diabetes remission after bariatric surgery. Patients achieving remission after 1 year had lower levels of baseline succinate (47.8 [37.6–64.6] µmol/L vs. 64.1 [52.5–82.9] µmol/L; P = 0.018). Moreover, succinate concentrations were significantly decreased 1 year after surgery (58.9 [46.4–82.4] µmol/L vs. 46.0 [35.8–65.3] µmol/L, P = 0.005). In multivariate analysis, the best logistic regression model showed that baseline succinate (odds ratio [OR] 11.3, P = 0.031) and the type of surgery (OR 26.4, P = 0.010) were independently associated with remission. The C-statistic for this model was 0.899 (95% CI 0.809–0.989) in the derivation cohort, which significantly improved the prediction of remission compared with current available scores, and 0.729 (95% CI 0.612–0.846) in the validation cohort. Interestingly, patients had a different response to the type of surgery according to baseline succinate, with significant differences in remission rates. CONCLUSIONS Circulating succinate is reduced after bariatric surgery. Baseline succinate levels have predictive value for diabetes remission independently of previously described presurgical factors and improve upon the current available scores to predict remission.
Sphingolipids as a novel target for the treatment of multiple myeloma.
Authors: Yubin Kang, Jagadish Kummetha Venketa
Journal: Journal of Clinical Oncology (2013)

e19534 Background: Multiple myeloma (MM) is the second most common hematological malignancy in the United States and accounts for ~10,600 deaths annually. MM remains an incurable disease and almost all patients will eventually relapse and become refractory to currently available therapeutic agents. There is an unmet need for better understanding the disease’s molecular pathways and for identifying novel therapeutic targets. Sphingolipid metabolism is being increasingly recognized as a key pathway in tumor cell proliferation and in tumor sensitivity to anticancer drugs. We hypothesize that altered sphingolipid metabolism plays an important role in the pathogenesis of MM, thus providing a novel target in the treatment of MM. Methods: We first assayed sphingolipid metabolism including sphingolipid metabolites and sphingolipid metabolizing genes in myeloma cell lines, in freshly isolated human primary CD138 + myeloma cells, and in publically available dataset. We then tested the efficacy of the selective SK2 inhibitor (ABC294640) and the SK2 shRNA in killing myeloma cells in vitro. Results: 1) Compared to immortalized B cells, the levels of pro-apoptotic ceramides were decreased whereas the proliferative sphingosine 1-phosphate (S1P) was increased in myeloma cell lines. 2) The expression of several key sphingolipid-metabolizing genes including sphingosine kinase (SK) 1 and 2 was altered in freshly isolated human primary bone marrow myeloma cells and in publically available microarray dataset. 3) The selective SK2 inhibitor (ABC294640) induces apoptotic cell death and inhibits myeloma cell growth with an IC 50 of ~20 μM in 9 myeloma cell lines. 4) Interestingly, OPM-1 myeloma cell line was extremely sensitive to ABC294640 with an IC 50 of &lt;5 µM whereas U266 myeloma cell line was resistant to ABC294640. SK2 shRNA induced apoptotic cell death in OPM-1, but not in U266 cells. We are currently investigating the molecular mechanisms underlying the resistance of U266 myeloma cells to ABC294640. Conclusions: Our data demonstrated that sphingolipid metabolism provides an attractive target in the treatment of refractory/relapased multiple myeloma.
Transcatheter Interventions for Severe TR Patients Presenting to a Tertiary Care Setting
Authors: Jonathan Curio, Giuseppe Lanzillo, Antonio Mangieri, Matteo Pagnesi, Claudio Montalto, Ozan M. Demir, Michele De Bonis, Eustachio Agricola, Antonio Colombo, Azeem Latib
Journal: Journal of the American College of Cardiology (2019)
Management of clinical stage (CS) I and II patients with non-seminomatous germ cell tumors of the testis (NSGCTT) avoiding upfront retroperitoneal lymph node dissection (RPLND)
Authors: A. Flechon, F. El Karak, C. Salas, M. Rivoire, J. Droz
Journal: Journal of Clinical Oncology (2007)

5090 Background: CS I, Is, IIa and IIb may be treated by either upfront RPLND or upfront medical management followed by RPLND in selected cases. We retrospectively analyzed the later approach. Methods: From 1993 to 2003, 225 NSGCTT patients CS I and Is, IIa, IIb were treated at our center. In total, 148 patients with CS I were managed by surveillance followed by CT and surgical exeresis of residual disease in case of relapse and 77 with CS Is, IIa and IIb underwent upfront chemotherapy and RPLND in case of residual masses. Median follow-up was 52 months for all patients (0.16–165 months). Results: In CS I: 47/148 (32%) patients relapsed: 22/42 (52%) patients with microvascular involvement versus 25/106 without (24%). The median time to relapse was 5 months (0.16–79 months). All relapsing patients received CT except one for whom we have no information. Twenty-two patients (46%) had RPLND. Two patients died, one probably of haemorrhage one month after RPLND and one in a car accident. In CS II: 4 (5%) patients had CS Is, 40 (52%) CS IIa and 33 (43%) CS IIb. Respectively 71 (92%), 5 (6.5%) and 1 (1,5%) patients had good, intermediate or poor prognosis according to the IGCCCG. All patients received cisplatin-based chemotherapy. Forty-one (53%) patients had RPLND after CT and one refused surgery for residual disease. Histological review showed a teratoma in 22 cases (54%), necrosis in 16 (39%) and residual active disease in 3 (7%). Six patients (8%) relapsed: 1 of them had a growing teratoma. One patient died of disease and all others are alive with no evidence of disease. In total, after medical management of CS I and II, avoiding primary RPLND, only 124 (55%) and 63 (28%) patients had eventually CT and RPLND respectively. Ninety-nine percent patients were cured. Conclusions: Upfront medical treatment of CS I and CS II NSGCTT is a good option which allows to avoid unnecessary CT and RPLND indications. [Table: see text] No significant financial relationships to disclose.
Abstract 3279: Short Term Outcomes In Heart Failure Patients, After Initiation Of Guideline Based Therapies Designed To Improve Performance Measures
Authors: Harischandra B Karunaratne, Elizabeth Hoyt, Danielle Johnson
Journal: Circulation (2007)

BACKGROUND Quality improvement measures in heart failure (HF) have been focused on improvement in four performance measures reported in the Hospitals Compare Website. It is unclear whether improvem...
Health care utilization and costs among HER2-negative, HR-positive, elderly women with metastatic breast cancer in the United States.
Authors: Manjiri Pawaskar, Sudeep Karve, Tapashi Dalvi, Keith L. Davis, Robert Deeter
Journal: Journal of Clinical Oncology (2013)

e11571 Background: Limited data exist on the cost burden of elderly women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer (MBC). We therefore assessed this cost burden in a retrospective analysis of the Surveillance, Epidemiology and End Results-Medicare database (2000-2009). Methods: Women aged ≥65 years diagnosed with MBC or early-stage breast cancer who progressed to MBC with HER2 negative, HR positive status were selected. MBC diagnosis date or date of progression to MBC was the index date. The study included non-HMO patients who had continuous Medicare (Part A and B) enrollment for ≥12 months before index date to death or end of database (2009). All-cause and MBC-related (claims for MBC diagnoses or MBC-related treatments) healthcare utilization and costs were assessed descriptively and then annualized based on follow-up duration. Results: In total, 13,170 women met the inclusion criteria (mean [SD] age 76.7 [7.0] years, 88% white, 77% both ER and PR positive). Mean [SD] post-index follow-up duration was 38.5 [28.1] months. On average, patients had 2.5 hospitalizations (mean length-of-stay: 16 days) and 3 emergency department (ED) visits. Mean [SD] annual all-cause costs (in 2011 $) per patient were $34,264 [$33,429], half of which $16,397 [$18,284] were attributable to MBC. Hospitalizations, hospital outpatient visits, and physician office visits accounted for over three-quarters of total all-cause costs (mean [SD]: $13,804 [$22,589] $4,171 [$6,509], and $8,676 [$11,065], respectively) and 75% of MBC-related costs (mean [SD]: $4,449 [$9,436], $2,844 [$5,383], and $5,799 [$9,945], respectively). Within MBC-related costs, mean [SD] annual costs of chemotherapy, radiation, and hormone therapy were $1,442 [$4,095], $1,872 [$4,086], and $579 [$1,197], respectively. Conclusions: Our findings indicate that HR positive, HER2 negative elderly women with MBC have a substantial economic burden on the Medicare system with primary costs drivers being inpatient, hospital outpatient and physician office visit costs.
Time to treat: A system redesign focusing on decreasing the time from suspicion of lung cancer to diagnosis in a community hospital
Authors: D. S. Lo, R. A. Zeldin, R. Skrastins, I. M. Fraser, H. Newman, A. Monavvari, Y. Ung, H. Joseph, T. Downton, J. Meharchand
Journal: Journal of Clinical Oncology (2007)

17005 Background: Multiple physician visits, numerous investigations, and serial wait times often result in a lengthy process from the onset of lung cancer-related symptoms until diagnosis. An unpublished retrospective chart review from a Toronto community hospital indicated suboptimal delays for patients from onset of symptoms until the diagnosis of lung cancer. Methods: The Time to Treat Program (TTT), consisting of a streamlined referral system and a clerical facilitator to fast-track patients through a diagnostic pathway algorithm, was designed for patients with clinical or radiological suspicion of lung cancer. Data on patient visits and investigations were collected. Pre- and post-implementation data on median wait times were compared. Results: From April 2005 to December 2006 over 120 physicians referred 188 females and 226 males. For the majority of patients (95.2%), the reason for referral was chest x-ray findings suspicious for lung cancer. After TTT implementation, the median time from suspicion of lung cancer to referral for specialist consultation decreased from 19.9 days to 10 days, and the median time from such referral to the actual consultation date decreased from 16.8 days to 5.3 days. The median time from specialist consultation to CT scan decreased from 52.1 days to 4 days and the median time from CT to diagnosis decreased from 39 days to 12.4 days. Overall, the median time from suspicion of lung cancer to diagnosis decreased from 127.8 days to 30 days. For 25% of the patients in the TTT it took 13 or fewer days from suspicion of lung cancer to diagnosis, while for 5% of the patients it took 90 days or more. Half of the patients in the TTT had a diagnosis by 24 days from the time of suspicion. Of all patients in the TTT, 33% were eventually diagnosed with lung cancer. The time from suspicion to diagnosis took longer for patients who eventually had confirmed lung cancer than those who did not: 36.5 days vs. 28.7 days. Conclusions: By addressing process issues in the work-up of lung cancer, the TTT was effective in shortening the time from suspicion of lung cancer to diagnosis and reduced time intervals at each step in the process. Earlier diagnosis of lung cancer may allow increased treatment options for patients. No significant financial relationships to disclose.
Assessment of Therapeutic Interventions and Lung Protective Ventilation in Patients With Moderate to Severe Acute Respiratory Distress Syndrome
Authors: Hiroko Aoyama, Kanji Uchida, Kazuyoshi Aoyama, Petros Pechlivanoglou, Marina Englesakis, Yoshitsugu Yamada, Eddy Fan
Journal: JAMA Network Open (2019)

A number of interventions are available to manage patients with moderate to severe acute respiratory distress syndrome (ARDS). However, the associations of currently available ventilatory strategies and adjunctive therapies with mortality are uncertain.To compare and rank different therapeutic strategies to identify the best intervention associated with a reduction in mortality in adult patients with moderate to severe ARDS.An electronic search of MEDLINE, MEDLINE In-Process/ePubs Ahead of Print, Embase, Cochrane Controlled Clinical Trial Register (Central), PubMed, and CINAHL was conducted, from database inception to May 29, 2019.Randomized clinical trials of interventions for adults with moderate to severe ARDS that used lung protective ventilation. No language restrictions were applied.Data were independently extracted by 2 reviewers and synthesized with Bayesian random-effects network meta-analyses.The primary outcome was 28-day mortality. Barotrauma was a secondary outcome.Among 25 randomized clinical trials evaluating 9 interventions, 2686 of 7743 patients (34.6%) died within 28 days. Compared with lung protective ventilation alone, prone positioning and venovenous extracorporeal membrane oxygenation were associated with significantly lower 28-day mortality (prone positioning: risk ratio, 0.69; 95% credible interval, 0.48-0.99; low quality of evidence; venovenous extracorporeal membrane oxygenation: risk ratio, 0.60; 95% credible interval, 0.38-0.93; moderate quality of evidence). These 2 interventions had the highest ranking probabilities, although they were not significantly different from each other. Among 18 trials reporting on barotrauma, 448 of 6258 patients (7.2%) experienced this secondary outcome. No intervention was superior to any other in reducing barotrauma, and each represented low to very low quality of evidence.This network meta-analysis supports the use of prone positioning and venovenous extracorporeal membrane oxygenation in addition to lung protective ventilation in patients with ARDS. Moreover, venovenous extracorporeal membrane oxygenation may be considered as an early strategy for adults with severe ARDS receiving lung protective ventilation.
Emerging Immune Targets for Treatment of Multiple Myeloma
Authors: Atif Sohail, Adeela Mushtaq, Ahmad Iftikhar, Azka Latif, Vikas Kapoor, Faiza Hassan Warraich, Sami Ullah Warraich, Mirza Zeeshan Baig, Ali McBride, Faiz Anwer
Journal: Blood (2017)
Parkinson’s disease in China: a forty-year growing track of bedside work
Authors: Gen Li, Jianfang Ma, Shishuang Cui, Yixi He, Qin Xiao, Jun Liu, Shengdi Chen
Journal: Translational Neurodegeneration (2019)

The number and health burden of Parkinson's disease increase rapidly in China. It is estimated that China will have nearly half of the Parkinson's disease population in the world in 2030. In this review, we present an overview of epidemiology and health economics status of Parkinson's disease across China and discuss the risk factors of Parkinson's disease and related complications. From the view of clinical research, we also discuss the current status of clinical trials, diagnostic biomarkers, treatment of Parkinson's disease, tertiary network and post-occupation education in Chinese Parkinson's disease clinics.