tbuckley/cabot-search huggingface dataset:
Evaluation of the Association Between Gastric Acid Suppression and Risk of Intestinal Colonization With Multidrug-Resistant Microorganisms
Authors: Roel P. J. Willems, Karin van Dijk, Johannes C. F. Ket, Christina M. J. E. Vandenbroucke-Grauls
Journal: JAMA Internal Medicine (2020)

Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome. Whether acid suppression increases the risk of colonization with multidrug-resistant microorganisms (MDROs) is unclear.To systematically examine the association of use of acid suppressants with the risk of colonization with MDROs and to perform a meta-analysis of current evidence.PubMed, Embase, the Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials were searched from database inception through July 8, 2019.Study selection was performed independently by 2 authors (R.P.J.W. and C.M.J.E.V.-G.) on the basis of predefined selection criteria; conflicts were resolved by consensus or by an adjudicator (K.v.D.). Human observational studies (case control, cohort, and cross-sectional) and clinical trial designs were selected if they quantified the risk of MDRO colonization in users of acid suppressants in comparison with nonusers.The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) recommendations were followed. Data were extracted independently by the same 2 authors, and adjudication was conducted when necessary. Risk of bias was assessed according to a modified Newcastle-Ottawa Scale. Pooled odds ratios (ORs) were estimated using random-effects models; heterogeneity was evaluated using the I2 method.The primary outcome measure was intestinal colonization with MDROs of the Enterobacterales order (producing extended-spectrum β-lactamases, carbapenemases, or plasmid-mediated AmpC β-lactamases), vancomycin-resistant enterococci, methicillin-resistant or vancomycin-resistant Staphylococcus aureus, or multidrug-resistant Pseudomonas or Acinetobacter species.A total of 26 observational studies including 29 382 patients (11 439 [38.9%] acid suppressant users) met the selection criteria. Primary meta-analysis of 12 studies including 22 305 patients that provided adjusted ORs showed that acid suppression increased the odds of intestinal carriage of MDROs of the Enterobacterales order and of vancomycin-resistant enterococci by roughly 75% (OR = 1.74; 95% CI, 1.40-2.16; I2 = 68%). The odds were concordant with the secondary pooled analysis of all 26 studies (OR = 1.70; 95% CI, 1.44-1.99; I2 = 54%). Heterogeneity was partially explained by variations in study setting and the type of acid suppression.Acid suppression is associated with increased odds of MDRO colonization. Notwithstanding the limitations of observational studies, the association is plausible and is strengthened by controlling for confounders. In view of the global increase in antimicrobial resistance, stewardship to reduce unnecessary use of acid suppressants may help to prevent MDRO colonization.
Tolerability of Antiseizure Medications in Individuals With Newly Diagnosed Epilepsy
Authors: Bshra Ali A. Alsfouk, Martin J. Brodie, Matthew Walters, Patrick Kwan, Zhibin Chen
Journal: JAMA Neurology (2020)

<h3>Importance</h3> Tolerability is a key determinant of the effectiveness of epilepsy treatment. It is important to evaluate whether the overall tolerability has improved. <h3>Objective</h3> To identify factors associated with poor tolerability of antiseizure medications (ASMs) and examine temporal changes in tolerability. <h3>Design, Setting, and Participants</h3> This was a longitudinal cohort study at a specialist clinic in Glasgow, Scotland. Patients with newly diagnosed and treated epilepsy between July 1982 and October 2012 were included from 2282 eligible individuals. They were followed up until April 2016 or death. Data analysis was completed in August 2019. <h3>Exposures</h3> Antiseizure medications. <h3>Main Outcomes and Measures</h3> Univariable and multivariable survival analyses were performed to examine associations between potential risk factors and development of intolerable adverse effects (AEs). Intolerable AE rates of the ASMs as the initial monotherapy were compared between 3 epochs (July 1982-June 1992, July 1992-June 2002, and July 2002-April 2016). <h3>Results</h3> Of 1795 patients, 969 (54.0%) were male, and the median (interquartile range) age was 33 (21-50) years. A total of 3241 ASMs were prescribed during the period, of which 504 (15.6%) were discontinued within 6 months owing to intolerable AEs. Children younger than 18 years had lower intolerable AE rates than adults (vs aged 18-64 years: adjusted hazard ratio [aHR], 1.58; 95% CI, 1.07-2.32; vs aged ≥65 years: aHR, 1.90; 95% CI, 1.19-3.02) while female individuals (aHR, 1.60; 95% CI, 1.30-1.96) and those who had more than 5 pretreatment seizures (aHR, 1.24; 95% CI, 1.03-1.49) were associated with having higher risk. For each ASM trial, the risk of intolerable AEs increased with the number of previous drug withdrawals due to AEs (aHR, 1.18; 95% CI, 1.09-1.28) and the number of concomitant ASMs (aHR, 1.31; 95% CI, 1.04-1.64). The proportion of second-generation ASMs prescribed as the initial monotherapy increased from 22.3% (33 of 148) in the first epoch to 68.7% (645 of 939) in the last (<i>P</i> &lt; .001). Although differences in intolerable AE rates and types of AEs were found between the ASMs, there was no difference in the overall intolerable AEs rates to the initial monotherapy across the 3 epochs (first: 10.1% [15 of 148]; second: 13.8% [98 of 708]; third: 14.0% [131 of 939];<i>P</i> = .41). <h3>Conclusions and Relevance</h3> In this cohort study, the increased use of the second-generation ASMs had not improved overall treatment tolerability. Greater effort to improve tolerability in ASM development is needed.
Analysis of prevalence and prognostic implications of early versus delayed PSA declines during radium-223 (Ra223) treatment among men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Amanjot Sidhu, Pawel Zalewski, Anil Kapoor, Neil Fleshner, Edward Chow, Urban Emmenegger
Journal: Journal of Clinical Oncology (2020)

117 Background: Ra233 is a well-tolerated, bone-seeking alpha emitter that prolongs the survival of men with mCRPC. Since there is a lack of validated biomarkers useful for disease monitoring during Ra223 therapy, we sought to characterize prostate-specific antigen (PSA) response patterns within a retrospective cohort study of real-world Ra223 treatment in four cancer centres across Ontario. Methods: Of 198 patients (pts) overall, 64 were not included due to incomplete data. The remaining 134 pts were grouped into (i) early PSA responders with a ≥30% PSA decrease (PSA30) within 12 weeks of treatment start, (ii) pts with an initial PSA flare followed by decreasing PSA, and (iii) non-responders. We analyzed the overall survival (OS) of these three cohorts using the Kaplan-Meier method and log-rank testing. Results: PSA30 responses were rare (n = 11; 8.2%), PSA flares were seen in 20.2% of pts (n = 27), but the majority of pts did not achieve a PSA response (n = 96; 71.7%). Of the pts identified as having a PSA flare, 11/27 (40.7%) presented with a post-flare PSA decrease below baseline, whereas in 16/27 (59.3%) the PSA decreased below the flare peak but not below baseline. 5/27 (18.5%) pts with a PSA flare achieved a PSA30. The median OS was not reached, 15.8 months and 14.7 months in responders, flare pts and non-responders, respectively (p &gt; 0.05). Similarly, one year OS was 90.9%, 67.7% and 63.9% in responders, flare pts and non-responders. Conclusions: PSA flares are seen in one fifth of men undergoing Ra223 therapy for mCRPC. Despite delayed PSA declines of varying degrees, the survival of PSA flare pts is comparable to men without any PSA decline.
Maternal Intrapartum Group B Streptococcal Prophylaxis and Childhood Atopic Disorders
Authors: Sagori Mukhopadhyay, Miren Dhudasia, William Quarshie, Matthew Bryan, Robert Grundmeier, Gerber Jeffery, Scott Lorch, Zaoutis Theoklis, Jonathan Spergel, Karen Puopolo
Journal: Journal of Allergy and Clinical Immunology (2020)
罕见疾病先天性厚甲症 (PC) 研究
Authors: A.G. Zieman, P.A. Coulombe
Journal: British Journal of Dermatology (2020)

根据国际先天性厚甲症 (PC) 研究登记处,PC 是一种罕见的皮肤病,影响全世界约 900 人。PC 是由称为角蛋白中间丝基因(角蛋白 6A、角蛋白 6B、角蛋白 6C、角蛋白 16 和角蛋白 17)的基因亚群中的遗传突变(异常)引起的,这些突变通常存在于毛囊等皮肤结构、甲床和汗腺。 PC 有很多症状,但最常见和最具破坏性的症状是掌跖角化病 (PPK),在手掌和/或足底形成疼痛、厚的胼胝样溃疡。 PC 或 PC 相关 PPK 无法治愈或无有效治疗。这种情况的原因很复杂,但其中包括该疾病是显性遗传的,胼胝难以渗透,基础病变(受累皮肤斑块)的分子学复杂且不断演变。 这篇文章由美国密歇根大学的研究人员撰写,旨在综述目前关于 PC 相关 PPK 病理生理学(指体内过程和改变)的知识,并提出开发潜在有效疗法的新策略。 PPK 进展至少有 3 个阶段。这些阶段中的每一个都具有可以靶向的不同分子特征。作者提出了针对 PPK 进展各个阶段的方法,以开发出一种有效的 PC 相关 PPK 的治疗方法。通过不断的努力可获得对该疾病的更多了解。 本摘要涉及研究: 先天性厚甲症相关掌跖角化病的病理生理学: 对皮肤上皮稳态和治疗途径的新见解
Preparedness and vulnerability of African countries against importations of COVID-19: a modelling study
Authors: Marius Gilbert, Giulia Pullano, Francesco Pinotti, Eugenio Valdano, Chiara Poletto, Pierre-Yves Boëlle, Eric D'Ortenzio, Yazdan Yazdanpanah, Serge Paul Eholie, Mathias Altmann, Bernardo Gutierrez, Moritz U G Kraemer, Vittoria Colizza
Journal: The Lancet (2020)
A combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy
Authors: Ajaybabu V. Pobbati, Wanjin Hong
Journal: Theranostics (2020)

The transcriptional co-regulators YAP and TAZ pair primarily with the TEAD family of transcription factors to elicit a gene expression signature that plays a prominent role in cancer development, progression and metastasis. YAP and TAZ endow cells with various oncogenic traits such that they sustain proliferation, inhibit apoptosis, maintain stemness, respond to mechanical stimuli, engineer metabolism, promote angiogenesis, suppress immune response and develop resistance to therapies. Therefore, inhibiting YAP/TAZ- TEAD is an attractive and viable option for novel cancer therapy. It is exciting to know that many drugs already in the clinic restrict YAP/TAZ activities and several novel YAP/TAZ inhibitors are currently under development. We have classified YAP/TAZ-inhibiting drugs into three groups. Group I drugs act on the upstream regulators that are stimulators of YAP/TAZ activities. Many of the Group I drugs have the potential to be repurposed as YAP/TAZ indirect inhibitors to treat various solid cancers. Group II modalities act directly on YAP/TAZ or TEADs and disrupt their interaction; targeting TEADs has emerged as a novel option to inhibit YAP/TAZ, as TEADs are major mediators of their oncogenic programs. TEADs can also be leveraged on using small molecules to activate YAP/TAZ-dependent gene expression for use in regenerative medicine. Group III drugs focus on targeting one of the oncogenic downstream YAP/TAZ transcriptional target genes. With the right strategy and impetus, it is not far-fetched to expect a repurposed group I drug or a novel group II drug to combat YAP and TAZ in cancers in the near future.
Achievement of Remission in Two Early Rheumatoid Arthritis Cohorts Implementing Different Treat‐to‐Target Strategies
Authors: Vibeke Norvang, Gina H. Brinkmann, Kazuki Yoshida, Siri Lillegraven, Anna‐Birgitte Aga, Joseph Sexton, Sara K. Tedeschi, Houchen Lyu, Ellen S. Norli, Till Uhlig, Tore K. Kvien, Maria D. Mjaavatten, Daniel H. Solomon, Espen A. Haavardsholm
Journal: Arthritis & Rheumatology (2020)

Objective The objective of this study was to compare achievement of remission in 2 early rheumatoid arthritis ( RA ) treat‐to‐target ( TTT ) cohorts, a tight control cohort with a target of stringent remission in a randomized controlled trial and an observational cohort targeting a looser definition of remission in clinical practice. Methods We analyzed data from the Aiming for Remission in Rheumatoid Arthritis: a randomised trial examining the benefit of ultrasound in a Clinical Tight Control regimen ( ARCTIC ) trial and the Norwegian Very Early Arthritis Clinic ( NOR ‐ VEAC ) observational study. Both were Norwegian multicenter studies that included disease‐modifying antirheumatic drug ( DMARD )–naive RA patients and implemented TTT . The target in the ARCTIC trial was remission defined as a Disease Activity Score ( DAS ) of &lt;1.6 plus 0 swollen joints on a 44‐joint count, while the target in the NOR ‐ VEAC study was the less stringent remission target of a DAS 28 of &lt;2.6. We assessed achievement of the study‐specific targets and compared the odds of achieving the American College of Rheumatology( ACR )/European League Against Rheumatism ( EULAR ) Boolean remission during 2 years of follow‐up. Results We included 189 patients from the ARCTIC trial and 330 patients from the NOR ‐ VEAC study. The study‐specific target had been achieved in more than half of the patients in each cohort at 6 months, increasing to &gt;60% at 12 and 24 months. The odds of achieving ACR / EULAR Boolean remission during follow‐up were higher in the ARCTIC trial than in the NOR ‐ VEAC study, with significant differences at 3 months (odds ratio 1.73 [95% confidence interval 1.03–2.89]), 12 months (odds ratio 1.97 [95% confidence interval 1.21–3.20]), and 24 months (odds ratio 1.82 [95% confidence interval 1.05–3.16]). Conclusion A majority of patients in both cohorts reached the study‐specific treatment targets. More patients in the ARCTIC trial than in the NOR‐VEAC study achieved ACR/EULAR Boolean remission during follow‐up, suggesting that targeting a more stringent definition of remission provides further potential for favorable outcomes of a TTT strategy.
Around 3% of 1,300 Levels Were Elevated during Infections in a Retrospective Review of 131 Beijing Hospital In-Patients with More than 24,000 Days of Clozapine Treatment
Authors: Can-Jun Ruan, Yan-Nan Zang, Yu-Hang Cheng, Chuan-Yue Wang, José de Leon
Journal: Psychotherapy and Psychosomatics (2020)
Quality and Safety in Healthcare, Part LXIV
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2020)

Abstract Burnout and other causes of a lack of well-being among radiology residents are a major problem. The American College of Radiology has developed a “Well-being Curriculum for Radiology Residency Programs,” which has many suggestions that should be helpful to residents in multiple specialties. The American College of Radiology is also collecting data on well-being in order to get benchmarking data and try to find out why some programs have more problems with decreased well-being than other programs. Wellness newsletters, providing social opportunities, insisting on professional behavior for all, fairness in work distribution, night float schedules, willingness to be flexible with work schedules, and retreats have also been advocated.
Blood platelet volume to predict treatment-specific outcomes of metastatic castration-resistant prostate cancer.
Authors: Wataru Fukuokaya, Takahiro Kimura, Fumihiko Urabe, Shoji Kimura, Kojiro Tashiro, Shunsuke Tsuzuki, Yusuke Koike, Hiroshi Sasaki, Kenta Miki, Shin Egawa
Journal: Journal of Clinical Oncology (2020)

242 Background: In the present guidelines for the management of metastatic castration-resistant prostate cancer (CRPC), it is unclear who benefits from androgen receptor axis-targeted agents (ARATs) or docetaxel as a first-line treatment. Methods: We conducted a single-institutional retrospective study to explore treatment-specific biomarkers for treatment response of metastatic CRPC. A cohort of 211 patients with metastatic CRPC treated with either ARAT (abiraterone acetate or enzalutamide) or docetaxel as a first-line treatment was evaluated. In addition to well-established biomarkers such as hemoglobin, neutrophil-to-lymphocyte ratio, alkaline phosphatase, and lactate dehydrogenase, we also assessed red cell distribution width, platelet count, and mean platelet volume (MPV). Laboratory measures were assessed within 1 month before starting treatment. Prostate-specific antigen progression-free survival (PSA-PFS) and radiographic progression-free survival (RPFS) were evaluated. Multivariable Cox regression models were used to assess the association between biomarkers and the risk of events. We also studied the statistical interaction between biomarkers and clinical outcomes. Results: Of all blood-based biomarkers, multivariable Cox regression models identified pre-treatment MPV (≤9.0 fL) as an independent prognostic factor of both PSA progression (hazard ratio [HR]: 2.62, 95% confidence interval [CI]: 1.25-5.48, P = 0.011) and radiographic progression (HR: 4.46, 95% CI: 1.79-11.1, P = 0.001). In addition, these models showed a lower risk of PSA progression (HR: 0.38, 95% CI: 0.15-0.96, P = 0.041) and radiographic progression (HR: 0.16, 95% CI: 0.05-0.50, P = 0.002) with docetaxel compared with ARAT when pre-treatment MPV was small. Conclusions: The present study identified MPV as a significant treatment-specific prognostic factor of PSA progression and radiographic progression in patients with metastatic CRPC treated with a first-line treatment. Furthermore, our results suggested that small MPV was associated with superior survival benefit on docetaxel over ARAT.
The Efficacy and Safety of Probiotic and Peanut Oral Immunotherapy for inducing Desensitization and Sustained Unresponsiveness: Results from a Phase 2b Multi-center Randomized Trial (PPOIT-003)
Authors: Paxton Loke, Adriana Chebar Lozinsky, Francesca Orsini, Molly O'Sullivan, Christine Axelrad, Susan Fahy-Scheer, Jessica Metcalfe, Dean Tey, Marnie Robinson, Ee-Lyn Su, Kuang-Chih Hsiao, Susan Prescott, Michael O’Sullivan, Patrick Quinn, Michael Gold, Mimi Tang
Journal: Journal of Allergy and Clinical Immunology (2020)
The use of intermittent enzalutamide dosing in the treatment of metastatic castrate-resistant prostate cancer.
Authors: Michael Rowe, Ayesha Hidayat, Stuart Walter, Adam Pollard, Timothy Norris, Deborah Victor, John McGrane, Alastair Thomson
Journal: Journal of Clinical Oncology (2020)

81 Background: Intermittent hormone manipulation in castrate-sensitive prostate cancer can improve quality of life whilst maintaining comparable disease outcomes with continuous scheduling. Enzalutamide is effective in metastatic castrate-resistant prostate cancer (mCRPC) treatment but can have significant side-effects. We conducted a retrospective analysis of patients treated with intermittent enzalutamide compared with continuous dosing. Methods: Patients prescribed enzalutamide for mCRPC at Royal Cornwall Hospital from September 2011 to February 2018 were included. Data was collected from electronic medical records, selecting patients with at least a 1 month treatment break. Kaplan-Meier analysis of overall survival from enzalutamide start (OS), time to PSA failure (TTF) and total enzalutamide treatment time (TTT) was calculated for intermittent and continuous responders (&gt;50% PSA drop), assigned significance level of 0.05. Results: 243 patients received enzalutamide, 110 (45%) were continuous responders and 29 (12%) had intermittent dosing. All patients treated intermittently had a PSA response prior to first treatment break, which was most commonly for fatigue (60%). 25% were still receiving enzalutamide. Median number of breaks was 1 (range 1-7), time on treatment was 70% and time to first break was 5 months. The intermittent group had significantly improved OS with median not reached, median OS for continuous responders was 19 months (HR 2.39, 95% CI 1.53-3.76, p=0.002). The intermittent group had prolonged TTF (median 13 vs 6 months, p=0.001) and TTT (median 30 vs 10 months, p=0.0003). Conclusions: Intermittent dosing of enzalutamide in these mCRPC patients does not adversely impact OS, increasing time patients remain on treatment. However, this was a small, retrospective, single-centre study; prospective trials are necessary to clarify the role of intermittent enzalutamide.[Table: see text]
Overall survival (OS) among Medicare beneficiaries receiving sipuleucel-T (sip-T) versus oral treatment for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Rana R. McKay, Scott C. Flanders, Christine Ferro, Kate Fitch, Michael Fabrizio, Michael Thomas Schweizer
Journal: Journal of Clinical Oncology (2020)

42 Background: Since the mCRPC treatment landscape is evolving, we examined real-world use and outcomes of sipuleucel-T (sip-T) and oral agents (abiraterone acetate and enzalutamide) in men with mCRPC. Methods: Using Medicare FFS Identifiable Research data, we identified mCRPC men with a qualifying prostate cancer diagnosis (ICD-9 185, ICD-10 C-61) and an initial treatment claim (abiraterone, cabazitaxel, docetaxel, enzalutamide, radium 223, sip-T) in 2014. Continuous Part A, B, and D eligibility and no HMO enrollment was required through 2017 or until death. mCRPC index date is the date of a mCRPC therapeutic claim. Using 4 groups (sip-T first line, oral first line, sip-T any line, and oral any line [no sip-T]), survival was estimated using Kaplan-Meier methods (unadjusted). Hazard ratios (HR) were estimated using Cox’s proportional hazards regression modeling. Results: During 2014, 14,482 eligible men had mCRPC drug claims. We studied 6,853 naïve mCRPC men with no treatment claim in the prior 12 months. Over 150 permutations of anti-cancer agents were identified. See table for patient characteristics. Sip-T was used 2+ line in 4.5% of men receiving orals 1st. Median overall survival was longer for men who received sip-T, regardless if used 1st line (35 mo) or in any line (35 mo), compared with oral 1st line use (21 mo) or an oral any time without sip-T (21 mo). Similar survival was seen after adjusting for baseline opioid use. While most received sip-T as 1st line, survival rates were higher in men receiving sip-T in any line (48%) compared to men who never received any sip-T (29%). Conclusions: In this analysis, sip-T use was associated with a 45% reduction in risk of death and 14 mo survival benefit in the Medicare FFS population regardless of when used. Real-world analyses like this provide insight into how to optimize sip-T use to treat prostate cancer.[Table: see text]