tbuckley/cabot-search huggingface dataset:
Importance of stratification when measuring quality of care: Results from the Project for an Ontario Women's Health Evidence-Based Report Card (POWER) study
Authors: M. K. Krzyzanowska, L. Barbera, L. Elit, R. Saskin, N. Yeritsyan, A. Bierman
Journal: Journal of Clinical Oncology (2009)

6573 Background: The goal of the POWER study is to improve health and reduce inequities among women of Ontario using population-based performance measurement. All selected indicators are stratified by sex, age, income and place of residence to determine whether there are disparities in performance associated with these factors. Results pertaining to cancer (CA) indicators are presented. Methods: A modified Delphi approach was used to identify performance measures spanning the disease spectrum from screening through follow-up care and feasible to be evaluated from administrative data. Most recently available data (2003–2005) from the Ontario Cancer Registry, Registered Persons, billing and hospital databases were then used to evaluate the selected measures stratified by above four factors. Results: Twenty-nine cancer-specific indicators were selected by the panel, majority of which related to processes of care: general indicators relevant to multiple cancers (3), screening (5), breast CA (5), lung CA (3), colorectal CA (4), gynecologic CA (4), and end-of-life care (5). Among measures relating to non-sex specific cancers, few sex-related differences in care were identified. Income-based differences in care were most pronounced among the screening indicators with individuals from low-income neighborhoods less likely to receive appropriate screening or follow-up after an abnormal screening test. Among measures relating to treatment, age was the factor most frequently associated with differences in care especially in regards to radiation- or chemotherapy-related processes of care. There were geographic differences in quality of care within the province along the entire trajectory of cancer care from screening through end-of-life care. Conclusions: Among the cancer quality indicators considered, few sex-based differences exist. However, factors such as age, income and where one lives are important predictors of care underscoring the importance of stratification by such factors when evaluating quality of care. Further work is necessary to determine whether these differences in processes of care affect outcomes and how to facilitate access to care by disadvantaged groups. No significant financial relationships to disclose.
Asthma reviews in children: what have we learned?
Authors: Mark L Levy, Louise Fleming
Journal: Thorax (2020)

Asthma is a complex chronic disease, characterised by intermittent respiratory symptoms, airway inflammation and reversible airflow obstruction, without the availability of a single confirmatory diagnostic test. Management of this disease involves many challenges for primary care physicians. These include diagnosis, monitoring, identifying risk and chronic as well as acute management; furthermore, it is challenging to maintain up to date knowledge of asthma to facilitate good quality patient education. Primary care clinicians with their limited availability of routine appointments, plus the vast spectrum of medical conditions they manage, are generalists and cannot be experts in every clinical condition. Although these health professionals develop skills in quickly assessing patients and making decisions for urgent or delayed management, the initial challenge is to accurately diagnose chronic diseases and second having the confidence and knowledge to manage these complex diseases in the community. In the case of asthma, diagnosis and monitoring are frequently based on reporting of symptoms, which are limited by their lack of specificity and patient recall.

Considerable controversy1 2 surrounds the recent UK recommendations3 that primary care physicians should include spirometry and fractional exhaled nitric oxide (FeNO) in diagnosing asthma in the UK. Neither quality assured spirometry nor FeNO is widely available in primary care. This is further complicated because asthma patients may have normal spirometry when tested and this would potentially need to be repeated on a number of occasions to demonstrate reversible airflow obstruction, which is totally impractical in primary (or secondary) care settings. Peak flow diaries are a practical alternative in these cases.4 5 In their prospective …
Circulating tumor cell counts (CTC) as prognostic of overall survival (OS) in SWOG S0421-docetaxel with or without atrasentan for metastatic castration resistant prostate cancer (mCRPC).
Authors: Nicholas J. Vogelzang, Benjamin Ely, Louis M. Fink, Amir Goldkorn, Catherine M. Tangen, Przemyslaw Twardowski, Peter J. Van Veldhuizen, Neeraj Agarwal, Michael Anthony Carducci, J. P. Monk, Ram H Datar, Mark Garzotto, Philip C. Mack, Primo Lara, Celestia S. Higano, Maha Hussain, David I. Quinn, Richard J Cote, Ian Murchie Thompson
Journal: Journal of Clinical Oncology (2012)

10503 Background: CTC are promising biomarkers in mCRPC but have not been prospectively validated for docetaxel treatment (Rx). Using CellSearch technology (J&amp;J), we enumerated CTC in this Phase 3 trial &amp; assessed prognostic value for OS. The aim of this correlative study nested within 0421 was to compare CTC via CellSearch technology to newer microfilter technologies (Cote &amp; Goldkorn PIs RO1 CA141077). Comparative data analysis is ongoing. Methods: CTC were drawn at baseline (d1) &amp; pre-cycle 2 (d21) of Rx &amp; shipped overnight to a central site for enumeration (CTC/7.5 ml). Cox regression evaluated the association between OS and (i) baseline CTC counts &amp; (ii) CTC dynamics (d1 to d21) in pts with good (&lt;5) vs. poor (&gt;=5) baseline CTC counts. Receiver operator characteristic (ROC) analysis and Characteristics &amp; Regression Trees (CART) were used to explore further prognostic CTC cutpoints for 2-yr survival. Results: Of 263 patients (pts) consented, 238 were evaluable at d1 &amp; 232 at d21. At d1 median CTC was 5 (range 0-5916) &amp; d1 CTC &lt; vs. &gt;= 5 was associated with baseline PSA (mean 99 vs. 320 ng/ml, p=0.004) and worse bone pain (36% vs. 51%, p=0.03). There was a significant difference in OS for d1 CTC &lt; vs. &gt;=5, with a hazard ratio (HR) of 2.92 (95% CI 1.92-4.43, p&lt;0.001) after adjustment for PSA &amp; other factors. In pts with low d1 CTC (&lt; 5), an increase in CTC was associated with shorter OS, HR 4.04 (95%CI 1.56-10.44, p=0.004); in pts with high d1 CTC (&gt;=5), a &gt;=2-fold decrease in CTC was associated with longer OS, HR 0.45 (95%CI 0.24-0.84, p=0.012); adjusting for risk factors. D1 CTC and 2-year survival had ROC AUC of 0.781. CART analysis identified prognostic subgroups based on CTC of 0, 1-5, 6-53, and &gt;53: (HR 0.36, 0.77,1.3 and 2.8). Conclusions: In this phase 3 trial, d1 CTC was prognostic of OS after risk factor adjustment. CTC dynamics from d1 to d21 were also prognostic of OS. These data are an exploratory subset analysis of the overall study. Yet, they comprise the largest docetaxel-based prospective cohort to date, which validates a 5 CTC prognostic threshold for OS &amp; identifies new potential prognostic subgroups that may extend the clinical utility of CTC enumeration in mCRPC.
“Matching” the “Mismatch” Repair–Deficient Prostate Cancer with Immunotherapy
Authors: Michael T. Schweizer, Evan Y. Yu
Journal: Clinical Cancer Research (2020)

Abstract Mismatch repair gene mutations are uncommon in advanced prostate cancer; however, in those harboring these alterations, immune checkpoint blockade can be effective. As such, assays that can accurately identify these men are critically important. Cell-free circulating tumor DNA–based sequencing approaches appear to be one viable approach for identifying these patients. See related article by Ritch et al., p. 1114
More than 80% of total knee replacements can last for 25 years
Authors: Rob Cook, Peter Davidson, Rosie Martin
Journal: BMJ (2019)

The study Evans JT, Walker R, Evans W, Blom AW, Sayers A, Whitehouse MR How long does a knee replacement last? A systematic review and meta-analysis of case series and national registry reports with more than 15 years of follow-up. Published on 16 February 2019 Lancet 2019;393:655-63 This study was supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000776/more-than-80-of-total-knee-replacements-can-last-for-25-years
State-Specific Prevalence and Characteristics of Frequent Mental Distress and History of Depression Diagnosis Among Adults with Arthritis — United States, 2017
Authors: Janae D. Price, Kamil E. Barbour, Yong Liu, Hua Lu, Nancy L. Amerson, Louise B. Murphy, Charles G. Helmick, Renee M. Calanan, Michelle Sandoval-Rosario, Claudine M. Samanic, Kurt J. Greenlund, Craig W. Thomas
Journal: MMWR Morbidity and Mortality Weekly Report (2020)
The influence of time to adrenaline administration in the Paramedic 2 randomised controlled trial
Authors: Gavin D. Perkins, Claire Kenna, Chen Ji, Charles D. Deakin, Jerry P. Nolan, Tom Quinn, Charlotte Scomparin, Rachael Fothergill, Imogen Gunson, Helen Pocock, Nigel Rees, Lyndsey O’Shea, Judith Finn, Simon Gates, Ranjit Lall
Journal: Intensive Care Medicine (2020)

To examine the time to drug administration in patients with a witnessed cardiac arrest enrolled in the Pre-Hospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest (PARAMEDIC2) randomised controlled trial. The PARAMEDIC2 trial was undertaken across 5 NHS ambulance services in England and Wales with randomisation between December 2014 and October 2017. Patients with an out-of-hospital cardiac arrest who were unresponsive to initial resuscitation attempts were randomly assigned to 1 mg intravenous adrenaline or matching placebo according to treatment packs that were identical apart from treatment number. Participants and study staff were masked to treatment allocation. 8016 patients were enrolled, 4902 sustained a witnessed cardiac arrest of whom 2437 received placebo and 2465 received adrenaline. The odds of return of spontaneous circulation decreased in both groups over time but at a greater rate in the placebo arm odds ratio (OR) 0.93 (95% CI 0.92–0.95) compared with the adrenaline arm OR 0.96 (95% CI 0.95–0.97); interaction OR: 1.03, 95% CI 1.01–1.05, p = 0.005. By contrast, although the rate of survival and favourable neurological outcome decreased as time to treatment increased, the rates did not differ between the adrenaline and placebo groups. The rate of return of spontaneous circulation, survival and favourable neurological outcomes decrease over time. As time to drug treatment increases, adrenaline increases the chances of return of spontaneous circulation. Longer term outcomes were not affected by the time to adrenaline administration. (ISRCTN73485024).
Incidence of Radioembolization-Induced Liver Disease and Liver Toxicity Following Repeat 90Y-Radioembolization
Authors: Mohammad Elsayed, Robert M. Ermentrout, Ila Sethi, Zachary L. Bercu, James R. Galt, Morgan Whitmore, David C. Brandon, David M. Schuster, Nima Kokabi
Journal: Clinical Nuclear Medicine (2019)

Purpose The complication profile following repeat 90 Y-radioembolization (RE) is not well understood, and repeat RE is sometimes avoided because of concerns for RE-induced liver disease (REILD) and liver toxicity. The purpose of this study was to examine the incidence of REILD and liver toxicity following repeat 90 Y-RE and to identify potential risk factors. Methods A retrospective analysis of patients undergoing repeat RE to the same hepatic lobe between 2013 and 2018 was performed. Baseline factors were evaluated as predictors of liver toxicity, mortality, and REILD, which was defined as the presence symptomatic ascites or jaundice in the absence of biliary obstruction within 8 weeks following RE. Post-RE complications were graded according to the Common Terminology Criteria for Adverse Events version 5. Results A total of 39 patients underwent repeat RE with 14 (35.9%) experiencing Common Terminology Criteria for Adverse Events toxicity of grade 2 or greater, 3 (10.3%) grade 3, and no grade 4 or greater. A Model for End Stage Liver Disease score of 8 or greater was associated with grade 2 toxicity or greater (26.7% vs 75%; P = 0.013). Only 3 patients (7.7%) experienced REILD due to symptomatic ascites without jaundice. Greater than 2 REs were associated with a greater rate of 6-month mortality (12% vs 58.3%, P = 0.003), 12-month mortality (28% vs 75%, P = 0.007), and REILD (0% vs 21.4%, P = 0.016). Age, sex, microsphere type, cirrhosis, Child-Pugh, and Eastern Cooperative Oncology Group status were not significantly associated with complications, REILD, or survival. Conclusions Repeat 90 Y-RE appears to be well tolerated with a low rate of high-grade adverse events and REILD.
Limited Conclusions Can Be Reached From Danish Randomized Clinical Trial of Supported Employment—Reply
Authors: Thomas Nordahl Christensen, Merete Nordentoft, Lene Falgaard Eplov
Journal: JAMA Psychiatry (2019)

In Reply We thank Mueser and McGurk for the interest in this Danish randomized clinical trial investigating the effects of individual placement and support (IPS) and IPS supplemented with cognitive remediation and social skills training among 720 participants with severe mental illness.1
Primary Care Physicians’ Experiences With and Strategies for Managing Electronic Messages
Authors: Tracy A. Lieu, Andrea Altschuler, Jonathan Z. Weiner, Jeffrey A. East, Mark F. Moeller, Stephanie Prausnitz, Mary E. Reed, E. Margaret Warton, Nancy Goler, Sameer Awsare
Journal: JAMA Network Open (2019)

<h3>Importance</h3> The increasing use of electronic communications has enhanced access to physicians for patients and clinical staff. Primary care physicians (PCPs) have anecdotally identified electronic inbox management as a new source of work-related stress. <h3>Objectives</h3> To describe PCPs' experiences managing their electronic inboxes and to characterize the array of management strategies developed by individual physicians and practice groups. <h3>Design, Setting, and Participants</h3> This qualitative study was conducted in 8 medical centers of a large group practice with more than 4 million patients in diverse settings and a mature electronic health record. The group encourages patients to use portal secure messaging to enhance access to their physicians and the care experience. Semistructured interviews were conducted with 24 internists and family medicine physicians identified via snowball sampling. Interviews were conducted July through November 2018. Data analysis was conducted between November 2018 and April 2019. <h3>Main Outcomes and Measures</h3> Audio recorded interviews were transcribed and analyzed using thematic analysis to identify major themes and subthemes. <h3>Results</h3> The 24 participants (12 women [50.0%]; mean [SD] age, 45.5 [6.5] years), including 9 department chiefs and 15 PCPs, had a mean (SD) of 16.8 (7.8) years since medical school graduation. Participants described substantial changes in medical practice due to electronic communication, including perceived patient expectations to receive rapid responses to portal secure messages. They described portal secure messaging as useful for building relationships with patients, but also reported that electronic message management has created new stressors, including erosion of work-life boundaries and anxiety associated with unlimited inbox volume. Individual PCPs used a diverse array of strategies, including multitasking during and outside work and delegating to medical assistants. Chiefs described group-level strategies, including reserving clinic time for inbox management, coverage systems for vacation and sick days, physician-to-physician training, and interdisciplinary teams to share messaging work. <h3>Conclusions and Relevance</h3> Individual physicians and local practice groups have developed a wide array of strategies for electronic inbox management. The volume of electronic messages and PCPs' perceptions that patients expect rapid responses have created new stressors in primary care practice. Medical groups and health systems can support PCPs by facilitating knowledge transfer among physicians about inbox management strategies and further developing team structures for inbox coverage.
Ambient particulate matter pollution and adult hospital admissions for pneumonia in urban China: A national time series analysis for 2014 through 2017
Authors: Yaohua Tian, Hui Liu, Yiqun Wu, Yaqin Si, Man Li, Yao Wu, Xiaowen Wang, Mengying Wang, Libo Chen, Chen Wei, Tao Wu, Pei Gao, Yonghua Hu
Journal: PLoS Medicine (2019)

Background The effects of ambient particulate matter (PM) pollution on pneumonia in adults are inconclusive, and few scientific data on a national scale have been generated in low- or middle-income countries, despite their much higher PM concentrations. We aimed to examine the association between PM levels and hospital admissions for pneumonia in Chinese adults. Methods and findings A nationwide time series study was conducted in China between 2014 and 2017. Information on daily hospital admissions for pneumonia for 2014–2017 was collected from the database of Urban Employee Basic Medical Insurance (UEBMI), which covers 282.93 million adults. Associations of PM concentrations and hospital admissions for pneumonia were estimated for each city using a quasi-Poisson regression model controlling for time trend, temperature, relative humidity, day of the week, and public holiday and then pooled by random-effects meta-analysis. Meta-regression models were used to investigate potential effect modifiers, including cities' annual-average air pollutants concentrations, temperature, relative humidity, gross domestic product (GDP) per capita, and coverage rates by the UEBMI. More than 4.2 million pneumonia admissions were identified in 184 Chinese cities during the study period. Short-term elevations in PM concentrations were associated with increased pneumonia admissions. At the national level, a 10-μg/m3 increase in 3-day moving average (lag 0–2) concentrations of PM2.5 (PM ≤2.5 μm in aerodynamic diameter) and PM10 (PM ≤10 μm in aerodynamic diameter) was associated with 0.31% (95% confidence interval [CI] 0.15%–0.46%, P < 0.001) and 0.19% (0.11%–0.30%, P < 0.001) increases in hospital admissions for pneumonia, respectively. The effects of PM10 were stronger in cities with higher temperatures (percentage increase, 0.031%; 95% CI 0.003%–0.058%; P = 0.026) and relative humidity (percentage increase, 0.011%; 95% CI 0%–0.022%; P = 0.045), as well as in the elderly (percentage increase, 0.10% [95% CI 0.02%–0.19%] for people aged 18–64 years versus 0.32% [95% CI 0.22%–0.39%] for people aged ≥75 years; P < 0.001). The main limitation of the present study was the unavailability of data on individual exposure to PM pollution. Conclusions Our findings suggest that there are significant short-term associations between ambient PM levels and increased hospital admissions for pneumonia in Chinese adults. These findings support the rationale that further limiting PM concentrations in China may be an effective strategy to reduce pneumonia-related hospital admissions.
Targeted Therapy of Acute Chest Syndrome with Recombinant Heme Oxygenase-1 Revealed By the Resistance of Young Transgenic Sickle Cell Mice to Heme-Induced Acute Lung Injury
Authors: Rimi Hazra, Samit Ghosh, Bethany Flage, Matthew Crouthamel, Clark Pan, Xiuxia Sun, Bohong Zhang, Joseph Sypek, Solomon Fiifi Ofori-Acquah
Journal: Blood (2019)
The Influence of Glycans-Specific Bioconjugation on the FcγRI Binding and <i>In vivo</i> Performance of <sup>89</sup>Zr-DFO-Pertuzumab
Authors: Delphine Vivier, Kimberly Fung, Cindy Rodriguez, Pierre Adumeau, Gary A. Ulaner, Jason S. Lewis, Sai Kiran Sharma, Brian M. Zeglis
Journal: Theranostics (2020)

Rationale: The overwhelming majority of radioimmunoconjugates are produced via random conjugation methods predicated on attaching bifunctional chelators to the lysines of antibodies. However, this approach inevitably produces poorly defined and heterogeneous immunoconjugates because antibodies have several lysines distributed throughout their structure. To circumvent this issue, we have previously developed a chemoenzymatic bioconjugation strategy that site-specifically appends cargoes to the biantennary heavy chain glycans attached to CH2 domains of the immunoglobulin's Fc region. In the study at hand, we explore the effects of this approach to site-specific bioconjugation on the Fc receptor binding and in vivo behavior of radioimmunoconjugates. Methods: We synthesized three desferrioxamine (DFO)-labeled immunoconjugates based on the HER2-targeting antibody pertuzumab: one using random bioconjugation methods (DFO-nsspertuzumab) and two using variants of our chemoenzymatic protocol (DFO-sspertuzumab-EndoS and DFO-sspertuzumab-βGal). Subsequently, we characterized these constructs and evaluated their ability to bind HER2, human FcγRI (huFcγRI), and mouse FcγRI (muFcγRI). After radiolabeling the immunoconjugates with zirconium-89, we conducted PET imaging and biodistribution studies in two different mouse models of HER2-expressing breast cancer. Results: MALDI-ToF and SDS-PAGE analysis confirmed the site-specific nature of the bioconjugation, and flow cytometry and surface plasmon resonance (SPR) revealed that all three immunoconjugates bind HER2 as effectively as native pertuzumab. Critically, however, SPR experiments also illuminated that DFO-sspertuzumab-EndoS possesses an attenuated binding affinity for huFcγRI (17.4 ± 0.3 nM) compared to native pertuzumab (4.7 ± 0.2 nM), DFO-nsspertuzumab (4.1 ± 0.1 nM), and DFO-sspertuzumab-βGal (4.7 ± 0.2 nM). ImmunoPET and biodistribution experiments in athymic nude mice bearing HER2-expressing BT474 human breast cancer xenografts yielded no significant differences in the in vivo behavior of the radioimmunoconjugates. Yet experiments in tumor-bearing humanized NSG mice revealed that 89Zr-DFO-sspertuzumab-EndoS produces higher activity concentrations in the tumor (111.8 ± 39.9 %ID/g) and lower activity concentrations in the liver and spleen (4.7 ± 0.8 %ID/g and 13.1 ± 4.0 %ID/g, respectively) than its non-site-specifically labeled cousin, a phenomenon we believe stems from the altered binding of the former to huFcγRI. Conclusion: These data underscore that this approach to site-specific bioconjugation not only produces more homogeneous and well-defined radioimmunoconjugates than traditional methods but may also improve their in vivo performance in mouse models by reducing binding to FcγRI.