tbuckley/cabot-search huggingface dataset:
Clinical focus and and funding characteristics of cancer trials registered in ClinicalTrials.gov.
Authors: Sayeedul Hasan, Amitasha Sinha, Rohit Anand, Aman Opneja, Anita Sivaraman, Shruti Bhandari, Kenneth David Miller
Journal: Journal of Clinical Oncology (2015)

e12631 Background: The relative distribution of the type and focus of funding for cancer research is changing. There is relatively little published data on the distribution of cancer trials and funding across various organ systems. Methods: The ClinicalTrials.gov website was searched for registered trials on cancer on August 7, 2014. The content of the registered trials was assessed for organ system, intervention, type of trial, funding source, and size. Trends were analyzed using Cochrane Armitage test. Results: A total of 44,861 clinical trials were reviewed. The number of unique registered trials increased significantly from 1042 in 2000 to 3810 in 2013. From 2000-2010, the highest number of clinical trials registered every year were for hematologic (Heme) malignancies; however, since 2011 the number of gastrointestinal-hepatic (GI/Hep) cancers increased significantly and constituted the largest proportion of clinical trials registered every year. Inspite of the change in trend, hematologic cancers account for > 20% of total number of cancer trials, followed by GI/hepatic (18%) and breast cancer (12%). The number of NIH/Federal funded trials decreased significantly over the last decade (p < 0.001), and non-government funded studies constituted nearly 70% of all registered trials. Federal and NIH funding was consistent with the ranking across organ systems with nearly 23% of government funding for heme malignancies. 84% of trials were interventional, of which 32% were drug trials, and nearly 40% were phase 2 trials. Only 7% of trials had published their results and 10% of trials were suspended or withdrawn. Conclusions: The number of cancer clinical trials has increased significantly in the last decade. Heme malignancy trials are most frequent followed by GI/hepatic and breast cancer trials. The percentage of federally funded trials has decreased during the study period. Many studies do not publish their results.
Metastasis-free survival as a predictor of overall survival in non-metastatic castration-resistant prostate cancer.
Authors: Richard Gagnon, Nimira S. Alimohamed, Eugene Batuyong, Alyssa Chow, Richard M. Lee-Ying
Journal: Journal of Clinical Oncology (2019)

201 Background: Recent trials have shown that apalutamide and enzalutamide can improve metastasis free survival (MFS) in advanced non-metastatic (M0) castrate-resistant prostate cancer (CRPC). MFS is a novel clinical endpoint, demonstrated to be a strong predictor of overall survival (OS) for localized prostate cancer, yet it is unknown if this is also true for M0 CRPC. Our aim was to determine how strongly MFS in M0 CRPC correlates with OS in a real world population. Secondary analyses evaluated whether a rapid PSA-doubling time (PSADT), of ≤10 months, impacts outcomes. Methods: We performed an analysis of patients diagnosed with advanced prostate cancer, followed at the Tom Baker Cancer Centre, in Calgary, Alberta from 2001-2017. Patients were excluded if they did not develop M0 CRPC. MFS and OS were measured using the Kaplan-Meier method and the log-rank test was used to compare outcomes based on PSADT. Correlation between OS and MFS was determined using Pearson Correlation and Kendall’s Tau-B. Results: A total of 1310 patients were identified with advanced prostate cancer, of which 87 developed M0 CRPC. The median age of diagnosis of M0 CRPC was 72 years, with a median Gleason score of 7.0, initial PSA of 10.4, and PSADT of 5.1 months. Only 6 patients were treated with second-generation anti-androgens or chemotherapy. Median MFS and OS after M0 CRPC diagnosis were 44.1 and 83.7 months, respectively. Pearson Correlation between MFS and OS was strong with a coefficient of 0.850 (p &lt; 0.001); with non-parametric Kendall’s Tau, correlation was also strong with a coefficient of 0.632 (p &lt; 0.001). PSADT ≤10 months was identified in 70 patients, and associated with a significantly shorter MFS, compared to a PSADT &gt; 10 months (40.2 vs. 90.4 months; p = 0.001), as well as shorter OS (76.2 vs. 104.3 months; p = 0.008). Conclusions: MFS for M0 CRPC is strongly correlated with OS in a real world population. PSADT of ≤10 months seems to be a useful prognostic tool in estimating MFS and OS in patients with M0 CRPC. MFS was better than expected even in patients with a PSADT of ≤10 months, which may due to our adherence to the biochemical definition of castration-resistant disease, as well as lack of standard imaging intervals in the real world.
Abstract P113: The Primordial Prevention Project: Pilot Study of Disclosing Child’s Diabetes Genetic Risk Information
Authors: Mitchell Smith, Jennifer Wessel
Journal: Circulation (2019)

The prevalence of type 2 diabetes (T2D) in children has risen dramatically. NHANES data of 12-19 years old showed a significant increase, from 9% to 23%, in pre-diabetes and diabetes from 1999-2008, which was related to increases in BMI. Lifestyle interventions in adults have been shown to be effective at reducing T2D risk, however, interventions in families have been inconclusive in demonstrating the benefit of lifestyle change in reducing T2D risk. We hypothesized that using child’s genetic risk information in families at high risk of developing T2D would serve as a motivator to improve behaviors related to risk factors for T2D. We conducted a pilot study of 44 families and their children aged 2-8 who consented to participate in baseline, risk-disclosure and 3-month follow-up sessions. We identified families as high risk based on a maternal history of gestational diabetes, large for gestational age, or paternal obesity. Parents were surveyed on their family’s physical activity and dietary behaviors, and attitudes and motivations for lifestyle change at baseline and 3-month follow-up. At baseline, saliva samples were collected from children for genotyping of variants previously associated with obesity and T2D risk in genome-wide association studies. When genotyping was completed families were then scheduled to receive results. Parents completed questionnaires related to their anxiety (STAI-State) and depressive symptoms (POMS) prior to receiving their child’s genetic risk and immediately after the intervention. Parents received their child’s genetic risk report, in combination with a quasi-motivational interviewing session and educational materials. At the end of the session parents set individualized behavior goals for themselves and their children based on their responses to baseline questionnaires related to dietary and PA behaviors. Follow-up at 3 months are still being collected. Results from the risk disclosure session are reported here. Parents were 35±5 years old; 11% Latino, 26% black and 63% White; and 60% were mothers. Parents reported a significant increase in fatigue (ß =0.98, p=0.001), depressiveness (ß=0.35, p=0.04), and anxiety (ß =3.0, p=0.001) from pre-risk disclosure compared to post risk-disclosure. Parents reported a significant increase in their confidence to change their family’s behaviors after receiving the intervention (ß=0.34, p=0.001). All parents committed to a personalized health behavior change after learning of their child’s risk. In conclusion, we were able to demonstrate that genetic risk may be a useful motivator to encourage parents to take immediate action to make improvements to their family’s health behaviors. Short-term follow-up results will determine whether changes were meaningful in actual behavior changes.
Measurement Floors and Dynamic Ranges of OCT and OCT Angiography in Glaucoma
Authors: Sasan Moghimi, Christopher Bowd, Linda M. Zangwill, Rafaella C. Penteado, Kyle Hasenstab, Huiyuan Hou, Elham Ghahari, Patricia Isabel C. Manalastas, James Proudfoot, Robert N. Weinreb
Journal: Ophthalmology (2019)
Typical hormone deprivation side effects compared to SM-88 therapy for rising PSA.
Authors: Benjamin Adam Gartrell, Giuseppe Del Priore, Avi S. Retter, Gerald H. Sokol, Alexander G Vandell, Mack Roach
Journal: Journal of Clinical Oncology (2019)

79 Background: Treatment for rising PSA non-metastatic prostate cancer (nmPC) includes multifaceted hormone therapies (HT) associated with increasing related toxicity; in aggregate the risk benefit ratio is not ideal. We report on the use before HT, of SM-88, a novel combination therapy (amino acid analogue, CYP3A4 inducer, mTOR inhibitor and catalyst) based on the Warburg effect without known hormone related toxicity. Methods: Prospective ongoing Phase II of SM-88 (230 mg po bid) in recurrent nmPC with rising PSA (PCWG3 definition), no radiographically identified metastases at baseline and detectable CTCs. Results: From Sept 2016 to Dec 2017, there have been 31 consented (34 planned) with 23 evaluable (completed &gt; 1 cycle). Mean age 68.9; BMI 28.7; 38% black and 62% post RT. Mean testosterone (T) rose from 319 to 382 ng/dl (p=.19). Typical HT related side-effects were not observed: 96% of subjects reported no hot flashes, 91% no gynecomastia, 83% interest and 61% activity in sex, 78% excellent or nearly so overall health and 74% excellent QOL on at least 50% of their EORTC questionnaires; weight (-0.2 kg), hct (0%), glu (+2 mg/dl), urinary N telopeptide (-4.2 nmol), MAP (normotensives -2 mmHg, hypertensives -3 mmHg), heart rate (-2.4 beats/min), QTc (-3 ms) with no newly emergent &gt;480 ms, serum Ca ++ (-0.006 mg/dL), LDH (+6.4 u/L), bsAlkPhos (+6.2 u/L), triglycerides (-5.2 mg/dL), total protein (0.05 g/dL) and albumin (0.02 g/dL). Neutrophil lymphocyte ratio decreased at the end of cycle 1 in 100% (n=5, median 2.4) of those who progressed to subsequent therapy vs 47% of those who did not (p=.05). AEs occurred in 16 subjects: 1 unrelated Grade (G) 3; 0 G 4; 14/26 G 1-2 possibly related to drug. No AEs were related to T levels. From initial diagnosis of PSA rise (median 9, 3-18 months), 96% (22/23) have remained metastases free and 78% (18/23) remained free of additional HT (p&lt;.05). There were no skeletal or cardiovascular events. Conclusions: SM-88 may be useful in delaying the start of HT. While on SM88 subjects did not report any T or therapy related AEs &gt;G2. SM88 may be useful in prostate cancer patients who are more sensitive or vulnerable to HT related toxicity while maintaining stable PSA values. Prospective trials are planned to confirm its utility. Clinical trial information: NCT02796898.
Differing contribution of methotrexate polyglutamates to adalimumab blood levels as compared with etanercept
Authors: Thierry Dervieux, Joel M Kremer, Michael E Weinblatt
Journal: Annals of the Rheumatic Diseases (2019)

Table 1 Multivariate analysis of anti-TNF steady state blood levels in relation to MTXPG levels after adjusting for dosage, obesity status, CRP levels, disease duration and previous anti-TNF Random adalimumab levels µg/mL (n=83) Random etanercept levels µg/mL (n=86) Total R 2 37.0% 8.8% Intercept 3.88±2.591.33±1.57RBC MTXPG 3 (nmol/L) 0.07±0.03(p=0.01)*-0.01±0.01(p=0.44)Anti-TNF dose (mg/week) 0.47±0.10(p<0.01)0.06±0.03(p=0.07)BMI >30 (kg/m 2 ) -4.26±1.33 (p<0.01)-0.18±0.49(p=0.72)CRP (mg/L) -0.46±0.16(p<0.01)-0.05±0.03(p=0.12)Disease duration (years) 0.05±0.07(p=0.50)-0.03±0.02(p=0.23)Previous anti-TNF -2.54±1.66(p=0.13)-0.06±0.77(p=0.94)*Each unit RBC MTXPG 3 (expressed as nmol/L) was associated with 0.09 units higher adalimumab levels (expressed as µg/mL).Estimates are given for each of the anti-TNFs as dependent variables with RBC MTXPG3, anti-TNF dose, obese status, CRP, disease duration and previous anti-TNFs as independent predictors.BMI, body mass index; CRP, C reactive protein; RBC MTXPG, red blood cells methotrexate polyglutamate; TNF, tumour necrosis factor.
Half of councils no longer provide universal specialist stop smoking services
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Almost half of England’s local councils no longer have a specialist stop smoking service for all smokers in their area as a result of government cuts to public health budgets, a new analysis has shown.1

The report from the charities Action on Smoking and Health (ASH) and Cancer Research UK found that 85 of 151 local authorities (56%) provided a universal specialist service in 2018-19, a drop from 61% the previous year. A further 13 (9%) provided only restricted specialist support to targeted groups of smokers, such as pregnant women and people with a mental health condition.

The charities said …
Inflammatory bowel disease and risk of prostate cancer: A matched-cohort analysis.
Authors: Adam Weiner, Jacob A Burns, William J Catalona, Eric Li, Edward M. Schaeffer, Stephen Hanauer, Scott Strong, James Burns, Maha H. A. Hussain, Shilajit Kundu
Journal: Journal of Clinical Oncology (2019)

55 Background: There are few data on the risk of prostate cancer (PCa) in men with inflammatory bowel disease (IBD) and there are no data comparing serum prostate-specific antigen (PSA) values between men with IBD and matched men without IBD. Methods: This study retrospectively matched men with IBD based on race and age 1 to 9 to men without IBD (controls) who underwent PCa screening with at least one PSA at a single academic medical center from 1996 to 2017. Kaplan-Meier and multivariable Cox analyses were used to compare the risk of any and clinically significant PCa (Gleason grade group &gt; 1) between the two groups adjusting for number of PSA tests, abnormal rectal exam, age, and race. A mix-effects regression was used to assess the association between PSA and IBD status. Results: After a median follow-up of 6.5 years for 1,033 men with IBD and 4.7 years for 9,306 controls, the median number of PSA tests was 2, 74% were white, and median age at first PSA (starting point of follow-up) was 53 years. At 10 years of follow-up, the incidence of any PCa was 0.65% for controls and 4.4% for men with IBD (HR 4.37, 95% CI 3.08-6.19, p &lt; 0.001) and of clinically significant PCa was 0.42% for controls and 2.4% for men with IBD (HR 3.78, 95% CI 2.40-5.96, p &lt; 0.001). When only men with IBD were assessed, use of biologic medications, duration of IBD diagnosis, history of bowel resection, Crohn’s disease versus ulcerative colitis were not associated with PCa diagnoses (all p &gt; 0.1). Any steroid treatment for IBD was associated with decreased incidence of any PCa (HR 0.22, 95% CI 0.06-0.78, p = 0.019), but not with clinically significant PCa (p = 0.5). PSA values were higher among men with IBD starting at age 60 (1.12 ng/mL vs 1.04 ng/mL, p = 0.031) and this gap widened with increasing age (age 70: 1.54 ng/mL vs 1.32 ng/mL, p = 0.007). Conclusions: Men with IBD being screened for PCa had an increased incidence of all and clinically significant PCa compared to age- and race-matched controls and had increased PSA values at older age. These findings should be further validated to consider IBD as a risk factor for PCa and optimize screening for this population.
Special, radical, failure of reduction in psychiatry
Authors: Don Ross
Journal: Behavioral and Brain Sciences (2019)

Abstract Use of network models to identify causal structure typically blocks reduction across the sciences. Entanglement of mental processes with environmental and intentional relationships, as Borsboom et al. argue, makes reduction of psychology to neuroscience particularly implausible. However, in psychiatry, a mental disorder can involve no brain disorder at all, even when the former crucially depends on aspects of brain structure. Gambling addiction constitutes an example.
Abstract 18784: Lamin A/C Regulates Transcription Factor and Epigenetic Gene Networks in the Heart
Authors: Priyatansh Gurha, Gaelle Auguste, Raffaella Lombardi, Suet Nee Chen, Tyrone Garnett, Kyle Chamberlain, Jalish M Riyad, Thomas Weber, Cristian Coarfa, Ali J Marian
Journal: Circulation (2017)

Introduction: Mutations in Lamin A/C (LMNA) are major causes of dilated cardiomyopathy (DCM). LMNA an inner nuclear membrane protein is considered to be essential for nuclear genome organization an...
Carbon Monoxide Toxicity
Journal: New England Journal of Medicine (1963)

Carbon monoxide (CO) is released into the environment by the incomplete combustion of carbonaceous materials. The sources of CO are plentiful, and except carbon dioxide (CO2), CO is the most abundant pollutant in the lower environment. It is tasteless, odorless, and colorless, and victims are usually rendered unconscious before they realize they are being poisoned. The effects of CO poisoning on humans are variable, and healthcare professionals are just beginning to understand these effects better.,,
Association between urinary, bowel, and hormonal treatment-related symptoms and clinical outcomes in nonmetastatic castration-resistant prostate cancer (nmCRPC): PROSPER study.
Authors: Fred Saad, Robert Morlock, Cristina Ivanescu, Jennifer Sugg, Bertrand F. TOMBAL
Journal: Journal of Clinical Oncology (2019)

233 Background: PROSPER data were analyzed to assess the relationship between time to worsening of urinary, bowel, and hormonal treatment-related symptoms and prostate-specific antigen (PSA) response, and the longitudinal association between symptom changes and metastasis-free survival (MFS). Methods: 1401 patients (pts) with nmCRPC at high metastasis risk were randomized 2:1 to enzalutamide (ENZA) or placebo. Urinary, bowel, and hormonal treatment-related symptoms were assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-PR25) at baseline (BL) and every 16 weeks. The association between time to first clinically meaningful symptom worsening and PSA response (≥50% decline from BL) was analyzed with stratified Cox regression using treatment as a covariate. Longitudinal symptom changes and MFS were evaluated in joint models using symptom scores as covariates, adjusted for treatment and clinical/demographic variables. The proportion of pts with improvement, no change, or deterioration at metastasis were analyzed by treatment group. Results: 723/1401 (52%) pts were PSA responders, including &gt;90% of ENZA pts. PSA responders were significantly less likely to develop urinary, bowel, and hormone treatment-related symptoms vs. non-responders (hazard ratio [HR] 0.58 [95% confidence interval 0.41, 0.81]; 0.59 [0.43, 0.80]; and 0.70 [0.51, 0.97], respectively). Every 9-point increase in urinary symptom score was associated with a 10% increased metastasis risk (HR 1.1 [1.05, 1.15]). Bowel and hormonal symptoms did not predict metastasis. Most pts reported no EORTC score changes at metastasis and maintained stable urinary/bowel symptoms, with no major observed symptom differences between treatment groups. Conclusions: ENZA delays metastasis and extends time to symptom worsening. A ≥50% PSA reduction from BL is associated with a reduction in risk for urinary, bowel, and hormonal treatment-related symptom worsening; changes in urinary symptoms from BL also predict metastases. Clinical trial information: NCT02003924 (PROSPER).
Did Medicare Part D reduce socioeconomic disparities in mortality? An analysis of breast cancer patients.
Authors: Liliana E Pezzin, Purushottam Laud, Emily McGinley, Ann Nattinger
Journal: Journal of Clinical Oncology (2015)

e17602 Background: A major goal of the Medicare Part D program was to enhance access to oral medications thereby reducing medication cost-related disparities in health outcomes. We examined whether the Medicare Part D program ameliorated socioeconomic (SES) disparities in overall and disease-specific 5-year survival among elderly women with incident breast cancer. Methods: Cumulative incidence functions by SES were calculated for all-cause and breast cancer specific mortality. Difference-in-differences logistic and competing risks regressions were applied to a pooled cohort of women identified as having breast cancer before (in 2001, N = 54,772) and after (in 2007, N = 46,371) enactment of Part D. SES indicators, obtained from individual and ecological data, identified women as poor, near-poor, medium and high income. Results: There were significant reductions in SES disparities in overall mortality among elderly breast cancer patients after implementation of the Part D program. Differences in the predicted probability of death from any cause across the 2001 and 2007 cohorts ranged from -6.9 (from 40.5% to 33.6%) and -5.5 (25.9% to 20.5%) percentage points for poor and near poor women to -1.9 percentage points (20.3% to 18.4%) for the high income group. The relative (to high income) post Part D improvements in survival among poor and near poor women were both substantial (nearly 4- and 3-fold) and statistically significant ( p < 0.004) . Although breast cancer mortality was lower, across all SES groups, for the post Part D cohort, there were no significant reductions in SES disparitiesacross the two cohorts. The adjusted predicted probability of breast cancer mortality declined by 1.9 (13.1 to 11.2%), 1.3 (8.8 to 7.5%) and 0.8 (6.3 to 5.5%) percentage points for poor, near poor and high income women, respectively. Conclusions: Our findings indicate that, although the Part D program was successful in ameliorating SES disparities in mortality and survival among breast cancer patients, gains were concentrated in causes of death other than breast cancer. This suggests remaining gaps in access to effective initial or followup care.
Rectal toxicity results for patients treated with HDR brachytherapy as monotherapy versus dose-escalated external beam radiotherapy for localized prostate cancer.
Authors: Jacob Samuel Parzen, Hong Ye, Gary S. Gustafson, Alvaro Martinez, Evelyn Sebastian, Amy Limbacher, Daniel J. Krauss
Journal: Journal of Clinical Oncology (2019)

5 Background: We present a large retrospective analysis comparing rectal toxicity following high dose rate (HDR) brachytherapy as monotherapy relative to dose-escalated external beam radiotherapy (EBRT) for patients with localized prostate cancer. Methods: 2683 patients treated with HDR or EBRT between 1994 and 2017 were included. 545 (20.3%) received HDR and 2138 (79.7%) EBRT. HDR fractionation was 38 Gy/4 fractions (n=321), 24 Gy/2 (n=96), or 27 Gy/2 (n=128). EBRT patients received a median dose of 75.6 Gy in 1.8 Gy fractions [range 70.2-82.8 Gy], using either 3D conformal or intensity modulated radiotherapy (IMRT). All EBRT patients underwent 3D image guidance via an off-line adaptive process. Treatment was directed to prostate only (n=780) or prostate and seminal vesicles (n=1351). No nodal therapy was given. Target volume for HDR patients included the prostate with no expansion. Acute and chronic gastrointestinal (GI) toxicity was defined as occurring ≤ 6 and &gt; 6 months, respectively, after radiotherapy and was graded per CTCAE version 3.0. Toxicity variables were analyzed with χ 2 test. Results: Median follow-up was 7.5 years (7.4 years for EBRT and 7.9 years for HDR). 69.1% of EBRT patients received IMRT with the remainder treated using 3D conformal technique. Compared to EBRT, HDR was associated with decreased rates of acute grade ≥ 2 diarrhea (0.7% vs. 4.5%, p &lt; 0.001), rectal pain/tenesmus (0.6% vs. 7.9%, p &lt; 0.001), and rectal bleeding (0% vs. 1.6%, p=0.001). Rates of chronic grade ≥ 2 rectal bleeding (1.3% vs. 8.7%, p &lt; 0.001) and radiation proctitis (0.9% vs. 3.3%, p=0.001) favored HDR over EBRT. Rates of any chronic rectal toxicity grade ≥ 2 were 2.4% vs. 10.5% (p &lt; 0.001) for HDR vs. EBRT, respectively. For the 1478 EBRT patients treated with IMRT, acute and chronic rates of any grade ≥ 2GI toxicity were 4.2% and 5.6%, respectively, compared to 1.5% (p=0.002) and 2.4% (p=0.002), respectively, for HDR patients. Conclusions: In appropriately selected patients with localized prostate cancer undergoing definitive radiation therapy, HDR brachytherapy as monotherapy is an effective strategy for reducing acute and chronic rectal toxicity.