tbuckley/cabot-search huggingface dataset:
Impact of FDA label change on immunotherapy for metastatic urothelial cancer (mUC) and subsequent changes in mortality.
Authors: Daniel Vader, Ravi Bharat Parikh, Haojie Li, Kentaro Imai, Rebecca A. Hubbard, Ronac Mamtani
Journal: Journal of Clinical Oncology (2022)

459 Background: In May 2017, atezolizumab and pembrolizumab (IO) received accelerated approval for first-line treatment of cisplatin-ineligible patients with mUC, irrespective of PDL1 test status. In June 2018, the FDA and EMA restricted IO to cisplatin-ineligible patients with PDL1 positive tumors based on early review of data from confirmatory trials which suggested decreased overall survival in patients with PDL1 negative tumors treated with IO. We assessed the impact of the FDA label change on clinical outcomes of mUC patients in routine care. Methods: We conducted a controlled interrupted time series analysis using the US Flatiron Health electronic health record-derived de-identified database. The study sample included patients from 280 cancer clinics nationwide diagnosed with mUC and compared patients potentially impacted by the label change (cisplatin ineligible patients initiating first-line IO or carboplatin-based chemotherapy) to a comparator group who would have been unaffected by the label change (patients initiating first-line cisplatin-based chemotherapy) from 01 April 2017 to 17 May 2018 (pre-label change) and 20 June 2018 to 01 March 2020 (post-label change), excluding a 30-day wash out period encompassing the time-period between the initial FDA safety alert (18 May 2018) and the official FDA label change (19 June 2018). We used Cox regression to estimate adjusted pre-/post-label change related mortality differences in patients receiving carboplatin-chemotherapy or IO, accounting for secular changes in survival through comparison with the cisplatin comparator group. Results: The study included 829 patients with mUC initiating treatment in the pre-label change period (582 IO or carboplatin, 247 cisplatin) and 1,184 patients in the post-label change period (849 IO or carboplatin, 336 cisplatin), respectively. The use of IO, carboplatin, and cisplatin was similar across time-periods (pre-label change: 44.4%, 25.8%, and 29.8%; post-label change: 48%, 23.6%, 28.4%); while PD-L1 testing increased (6.6% to 28.1%). In adjusted models, there were no differences in survival in any of the groups following the FDA label change policy (table). Conclusions: The U.S. FDA label restriction on first-line immunotherapy was associated with increased PD-L1 testing but was not associated with changes in treatment patterns or improved mortality among patients with mUC.[Table: see text]
Proportional mortality among vinyl chloride workers
Authors: Richard R. Monson, John M. Peters, Maurice N. Johnson
Journal: Environmental Health Perspectives (1975)

In a proportional mortality analysis of 161 deceased workers in two plants processing or producing vinyl chloride, a 50% excess of deaths due to all cancer was seen. Specific sites of cancer with the greatest excess included liver and biliary tract, lung and brain. The excess in fatal cancer was seen mainly in men who died before age 60. Also, there was a trend in time in the ratio of observed to expected deaths: since 1970 over twice as many cancer deaths as expected have occurred.
An integrative paleolimnological approach for studying evolutionary processes
Authors: Maria Cuenca-Cambronero, Colin J. Courtney-Mustaphi, Ryan Greenway, Oliver Heiri, Cameron M. Hudson, Leighton King, Kimberley D. Lemmen, Marvin Moosmann, Moritz Muschick, Nare Ngoepe, Ole Seehausen, Blake Matthews
Journal: Trends in Ecology & Evolution (2022)
Mortality among US veterans after emergency visits to Veterans Affairs and other hospitals: retrospective cohort study
Authors: David C Chan, Kaveh Danesh, Sydney Costantini, David Card, Lowell Taylor, David M Studdert
Journal: BMJ (2022)

Abstract Objective To measure and compare mortality outcomes between dually eligible veterans transported by ambulance to a Veterans Affairs hospital and those transported to a non-Veterans Affairs hospital. Design Retrospective cohort study using data from medical charts and administrative files. Setting Emergency visits by ambulance to 140 Veteran Affairs and 2622 non-Veteran Affairs hospitals across 46 US states and the District of Columbia in 2001-18. Participants National cohort of 583 248 veterans (aged ≥65 years) enrolled in both the Veterans Health Administration and Medicare programs, who resided within 20 miles of at least one Veterans Affairs hospital and at least one non-Veterans Affairs hospital, in areas where ambulances regularly transported patients to both types of hospitals. Intervention Emergency treatment at a Veterans Affairs hospital. Main outcome measure Deaths in the 30 day period after the ambulance ride. Linear probability models of mortality were used, with adjustment for patients’ demographic characteristics, residential zip codes, comorbid conditions, and other variables. Results Of 1 470 157 ambulance rides, 231 611 (15.8%) went to Veterans Affairs hospitals and 1 238 546 (84.2%) went to non-Veterans Affairs hospitals. The adjusted mortality rate at 30 days was 20.1% lower among patients taken to Veterans Affairs hospitals than among patients taken to non-Veterans Affairs hospitals (9.32 deaths per 100 patients (95% confidence interval 9.15 to 9.50) v 11.67 (11.58 to 11.76)). The mortality advantage associated with Veterans Affairs hospitals was particularly large for patients who were black (−25.8%), were Hispanic (−22.7%), and had received care at the same hospital in the previous year. Conclusions These findings indicate that within a month of being treated with emergency care at Veterans Affairs hospitals, dually eligible veterans had substantially lower risk of death than those treated at non-Veterans Affairs hospitals. The nature of this mortality advantage warrants further investigation, as does its generalizability to other types of patients and care. Nonetheless, the finding is relevant to assessments of the merit of policies that encourage private healthcare alternatives for veterans.
Fibroblast growth factor 21: A “rheostat” for metabolic regulation?
Authors: Qin-Ying She, Jing-Fu Bao, Hui-Zhen Wang, Huixin Liang, Wentao Huang, Jing Wu, Yiwen Zhong, Hanxin Ling, Aiqing Li, Shu-Lan Qin
Journal: Metabolism (2022)
Glandular Fever
Authors: R. J. Lumsden
Journal: BMJ (1943)

Pernicious Anaemia treated with Pyloroduodenal Extract and Liver in Tablet Form Parenteral liver therapy is occasionally complicated by severe reactions.These may take the form of local pain or general effects such as headache, flushing, urticaria, dyspnoea, and even collapse.They are usually overcome by injecting minute doses of liver extract-1/250 c.cm., 1/25 c.cm., and 1/2 c.cm.-at intervals, together with adrenaline.A nervous patient, upset by the.reaction, may refuse further injections, and in such a case resort must be had to an oral preparation.An order made by the Minister of Health prohibits the oral use of liver extract as such, but in this preparation the liver is unextracted.It was tested on the following untreated case of pernicious anaemia.
Letter from Westminster
Authors: W. Russell
Journal: BMJ (1981)

The Social Services Committee's study of medical manpower and education grinds on.After the BMA's appearance-on which I reported last week (p 1004)-it was the turn of the Medical Women's Federation and the Hospital Consultants and Specialists Association.The HCSA's evidence was to the point: their representatives would have nothing to do with any proposal to increase the length of training as a way of tackling the problem.It was "unacceptable," they said.As for increasing the number of consultant posts, it would be costly, cause a complete change in the nature of the consultant's work, and tend to lower standards by eliminating competition.Their views made a fascinating contrast with those of the Medical Women's Federation who preceded them.The women were all for increasing consultant numbers and were remarkably optimistic about the possibilities for acceptance of change by consultants.Dr Susan Roberts, a consultant physician at Preston Hospital, argued that there was a misunderstanding among many consultants.The change in the number of juniors would mean not that they would be doing all their previous work plus that of the registrar but a different job looking after a smaller number of patients."I think pilot schemes have to be set up," she said."The results have to be published.The very real worries consultants have must be exposed and discussed to show that, when it comes down to it, it is not as terrible as all that."She argued that doctors did change their minds, but they did so by seeing that colleagues had found a good idea, looking at the evidence, and considering it.When the evidence was shown to them that something worked, she believed they would think about accepting change."The pilot scheme must be in the acute services," she said."You don't want to pick out an easy operation.It must be a difficult one.The imbalance is greatest in the acute services.
Primary urethral cancer: A GETUG French nationwide cohort study.
Authors: Ilfad Blazevic, Aude Flechon, Geraldine Pignot, Benoît Mesnard, Jerome Rigaud, Mathieu Roumiguié, Michel Soulie, Constance Thibault, Laurence Crouzet, Camille Goislard De Monsabert, Felix Lefort, Marine Gross-Goupil, Lucas Campedel, Mathieu Laramas, Elodie Martin, Leonor Chaltiel, Damien Pouessel
Journal: Journal of Clinical Oncology (2022)

430 Background: Primary urethral cancer (PUC) is a rare and heterogeneous malignancy. Due to its scarcity, little data are available on the optimal treatment sequence and survival, especially in metastatic patients. Methods: Data from patients diagnosed with a PUC between 01/01/2000 and 12/31/2018 were retrospectively collected from nine French referral centers. Survival rate were estimated with the Kaplan-Meier method and prognostic factors were analyzed using the Cox proportional hazards model and the log-rank test. In order to increase the statistical power of survival analysis in the metastatic stage, patients with synchronous and metachronous metastatic disease were pooled. Results: We identified 44 (62%) males and 27 (38%) females with a PUC. The most frequent histological types were urothelial carcinomas (40.0%), squamous cell carcinomas (34.3%) and adenocarcinomas (14.3%). Twenty-five (35.2%) patients were diagnosed at a localized stage (≤ T2, N0, M0); 35 (49.3%) at a locally advanced stage (≥ T3 or ≥ N1, M0) and 11 (15.5%) at a distant stage (M1). Twenty-seven patients had a metachronous metastatic cancer. Multimodality therapy was used in 24.0% and 57.1% of the patients with a localized and locally advanced disease, respectively. In the entire cohort, median overall survival (OS) was 52.5 months (IC95% 32.2 – 64.1) and stage at diagnosis was a predictor of OS (p &lt; 0.0001). For the 60 patients with a non-metastatic disease, 39 (65%) had a recurrence or were dead and the median disease-free survival (DFS) was 21.2 months (IC95% 16.8 – 34.5). Nodal involvement was the only factor associated with DFS (HR: 2.03, p = 0.0390). Multimodal treatment compared with unimodal treatment was not significantly associated with DFS (HR: 1.22, p = 0.5419). Regarding survival of the 38 metastatic patients, the median OS was 15.2 months (IC95% 8.2 – 23.5) and the median progression-free survival was 6.4 months (IC95% 4.4 – 9.8). Conclusions: This retrospective study showed an important heterogeneity in terms of histology, stage at diagnosis, and treatment of PUC. In this cohort, the multimodal approach did not show any improvement in survival of non-metastatic patients. This study is one of the few to describe the survival in metastatic patients.
Gallstone disease.
Authors: M. J. Harman
Journal: BMJ (1968)

BRiTtsH 513 of the liver cells except for those around the portal tracts, which appeared normal.The centrilobular zones were very haemorrhagic, the mid-zonal sinusoids were distended with blood, but the surviving outer zones were not congested.Her oliguric renal failure continued and was treated with intracaval 20% mannitol at first and 40% dextrose.She continued to deteriorate, however, and became comatose.Despite peri- tzneal dialysis for her renal failure, supervised by Dr. H. M. Leather, she did not improve and died on 13 December 1967.
Contemporary treatment and survival differences in patients with urothelial versus nonurothelial bladder and upper tract carcinomas: Analyses from the National Cancer Database (NCDB).
Authors: Jeanny B. Aragon-Ching, Hongkun Wang
Journal: Journal of Clinical Oncology (2022)

463 Background: Non-urothelial bladder and upper tract cancers are known to have worse prognosis than urothelial cancers. Further descriptive analyses of patterns of demographic presentation, stage, metastases and response to chemotherapy and immunotherapy are explored through the NCDB database. Methods: The primary objective of this retrospective review is to evaluate trends and differences between upper tract urothelial cancers (UTUC) versus non-urothelial (nUTUC) histologies (squamous, sarcomatoid, small cell or neuroendocrine, adenocarcinoma) and bladder urothelial cancer (UC) and bladder non-urothelial cancer (nUC) and compare the demographics, disease characteristics, treatment, incidence of stage and survival according to NCDB. Results: Data from diagnosis in year 2004 – 2017 were extracted from the NCDB. A total of 649939 cases of whom 630423 were urothelial and 19516 were non-urothelial for both bladder and upper tract cancers were identified. More men were diagnosed with urothelial carcinoma, UTUC (62%) and bladder UC (75%). The median age was similar for both groups, 71.4 years (UC) and 70.1 years (nUC). Majority were Caucasian at 91.6% (UC) and 85.7% (nUC) while African-American patients consisted of 5.26% in the UC and 10.8% in the nUC cohorts. Primary surgery occurred more frequently in the UC cohort (94.7%) compared to the nUC (87%). More patients were diagnosed with stage IV cancer in the nUC group (21.9%) compared to UC at 4.6%, and overall survival was slightly worse with nUC for stage IV cancers with median OS of 7.92 mos (CI, (7.75, 8.08) for UC vs 6.14 mos (CI, (5.78, 6.47) nUC; logrank p = &lt; 0.001, although the biggest numeric difference was in the stage 0 and stage I patients with mOS of 110.13 mos (CI, 109.44, 110.82) versus 46.09 mos (CI, 42.09, 50.66), p &lt; 0.001. Use of chemotherapy resulted in improved overall survival in the UC group with mOS of 73.53 mos (CI, 72.61, 74.41) compared to nUC at 17.28 mos (CI, (16.59, 17.87), p &lt; 0.0001 and use of immunotherapy similarly yielded improvement in the UC group with mOS of 115.98 mos (CI, 114.33- 117.65) compared to nUC at 64.49 mos (CI, 45.67, 88.51); p &lt; 0.0001. Conclusions: Urothelial cancer of both bladder and upper tract origin compared to non-urothelial cancers tend to have better prognosis in both presentation at diagnosis and with early stage cancers as well as treatment in advanced stages with chemotherapy or immunotherapy, highlighting the need for better therapeutic strategies for non-urothelial cancers.
Correction: Physiotherapy and intermittent positive-pressure ventilation of chronic bronchitis
Authors: R Sandler, G Roberts, D Voak, J Darnborough, A Heeley
Journal: BMJ (1978)

valproate binds to a macromolecule, producing an immunogenic structure.The antibody is directed against platelets because of their membrane fatty acids, which are chemically and configuratively similar to those of valproate.We suggest that all patients whose valproate assay exceeds the recommended concentration have regular platelet counts performed.
Safety and target engagement of an oral small-molecule sequestrant in adolescents with autism spectrum disorder: an open-label phase 1b/2a trial
Authors: A. Stewart Campbell, Brittany D. Needham, Christopher R. Meyer, Joanna Tan, Mary Conrad, Gregory M. Preston, Federico Bolognani, Srinivas G. Rao, Helen Heussler, Rebecca Griffith, Adam J. Guastella, Amy C. Janes, Blaise Frederick, David H. Donabedian, Sarkis K. Mazmanian
Journal: Nature Medicine (2022)
The Premenstrual Syndrome
Authors: R. Greene, K. Dalton
Journal: BMJ (1953)

<h3>Abstract</h3> <h3>Objective</h3> Electroencephalography (EEG) interpretations through visual (by human raters) and automated (by computer technology) analysis are still not reliable for the diagnosis of non-convulsive status epilepticus (NCSE). This study aimed to identify typical pitfalls in the EEG analysis and make suggestions as to how those pitfalls might be avoided. <h3>Methods</h3> We analyzed the EEG recordings of individuals who had clinically confirmed or suspected NCSE. Epileptiform EEG activity during seizures (ictal discharges) were visually analyzed by two independent raters. We investigated whether unreliable EEG visual interpretations quantified by low inter-rater agreement can be predicted by the characteristics of ictal discharges and individuals’ clinical data. In addition, the EEG recordings were automatically analyzed by in-house algorithms. To further explore the causes of unreliable EEG interpretations, two epileptologists analyzed EEG patterns most likely misinterpreted as ictal discharges based on the differences between the EEG interpretations through the visual and automated analysis. <h3>Results</h3> Short ictal discharges with a gradual onset (developing over 3 seconds in length) were liable to be misinterpreted. An extra 2 minutes of ictal discharges contributed to an increase in the kappa statistics of &gt; 0.1. Other problems were the misinterpretation of abnormal background activity (slow wave activities, other abnormal brain activity, and the ictal-like movement artifacts), continuous interictal discharges, and continuous short ictal discharges. <h3>Conclusion</h3> A longer duration criterion for NCSE-EEGs than 10 seconds that commonly used in NCSE working criteria is needed. Using knowledge of historical EEGs, individualized algorithms, and context-dependent alarm thresholds may also avoid the pitfalls.
On Sterility
Authors: A. W. Edis
Journal: BMJ (1882)

smIll and weak.This was immediately followed by a considerable increase in the quantity of urine, which rose to 130 ounces on the 13th and 20th.The codeia was resumed on the 2ISt, in doses of four grains and a half, and on the 30th was increased to nine grains daily, with the same result as before-an immediate fall in the urine from 130 to go ounces.On July 5th, morphia (half a grain three times a day) was substi- tuted for the codeia, and a few days later in grain doses, whereupon he was made an out-patient, and ordered to continue the morphia and cod-liver oil steadily for a month.These three cases all exhibited marked improvement whilst taking codeia, which improvement ceased when the codeiawas withheld, and was renewed on its repetition.Morphia had a good effect in two of the cases; but the improvement was much less marked with it than with the other alkaloids.
Abstract 118: The Epidemiology of Airway Management Following Pediatric Out-of-Hospital Cardiac Arrest in the United States
Authors: Maryam Y Naim, Heather Griffis, Robert A Berg, Richard N Bradley, Matthew L Hansen, David Markenson, Bryan F McNally, Vinay M Nadkarni, Kimberly Vellano, Joseph W Rossano
Journal: Circulation (2018)

Introduction: Bag mask ventilation (BMV) has been associated with improved survival following out of hospital cardiac arrest (OHCA), however advanced airway placement remains part of pre-hospital protocols for many emergency medical services (EMS) agencies. Hypothesis: To characterize airway management for pediatric OHCA and assess whether BMV alone vs. BMV plus advanced airway (supraglottic airway or tracheal intubation) is associated with neurologically favorable survival. Methods: Analysis of the Cardiac Arrest Registry to Enhance Survival database. Inclusion criteria were age ≤ 18 years, non-traumatic OHCA from 2013 through 2017, resuscitated by EMS. To adjust for covariate imbalance, propensity score matching and entropy balancing were utilized; variables included age category, sex, bystander CPR, and shockable rhythm. The primary outcome was favorable neurologically favorable survival defined as a cerebral performance category scale of 1 or 2. Results: Of 5241 cardiac arrests, 2588 (49.3%) had BVM and 2653 (50.6%) had advanced airway placement. The majority 5118 (97.7%) were resuscitated by agencies using both BMV and advanced airways. Advanced airway placement was more common in older children compared to infants, arrests with bystander CPR, in white and Hispanic children, witnessed arrests, arrests with a shockable rhythm, and AED use (Table). Neurologically favorable survival was significantly higher with BMV compared to advanced airways in bivariate analysis (11.4% vs. 5.7%, p&lt;0.001). In multivariable analysis, advanced airway placement was associated with lower neurologically favorable survival (adjusted proportion 4.9% vs. 13.5% BVM, OR 0.21, 95% CI 0.17, 0.28). These results were robust on propensity analysis 3.0% advanced airway vs.11.9% BMV (OR 0.18, 95% CI 0.14, 0.25), and entropy balance 5.9% advanced airway, 15.0% for BMV (OR 0.28, 95% CI 0.22). Conclusion: In pediatric OHCA, advanced airways are placed in half of cardiac arrests where resuscitation is attempted. Advanced airway, compared to BMV alone management, is associated with lower neurologically favorable survival.
Coherence-based connectivity analysis of EEG and EMG signals during reach-to-grasp movement involving two weights
Authors: Cristian D. Guerrero-Mendez, Andres F. Ruiz-Olaya
Journal: Brain-Computer Interfaces (2022)

Corticomuscular coherence allows studying the mechanism of the cerebral cortex's control of muscle activity, which reveals the communication in corticospinal pathways between the primary motor cortex and muscles. The present study aims to quantify the connectivity between the motor cortex (EEG signals) and five muscles of the right upper limb (EMG signals) during the manipulation of an object. A public dataset (WAY-EEG-GAL) was used which recorded EEG and EMG of twelve healthy subjects who performed movements of reaching, grasping, holding, and replacing objects of two different weights. Corticomuscular connectivity was established using the coherence algorithm for 3 EEG channels and 5 upper-limb muscles varying two objects' weights (0.165 kg and 0.660 kg). Results show that the 0.165 kg weight shows greater coherence between the signals for all analyses than the 0.660 kg weight. Furthermore, the results show that there is a contralateral and ipsilateral behavior in the EEG-EMG coherence.
Alcohol Consumption in a Healthy Population
Authors: Laure Papoz
Journal: JAMA (1981)

We analyzed the multivariate relationship between alcohol consumption and γ-glutamyl-transferase (GGT), mean corpuscular volume (MCV), and tobacco consumption. A group of 995 healthy outpatients (604 men and 391 women, 18 to 76 years old) were systematically examined. Daily alcohol consumption was established after an interview regarding complete dietary habits. Significant correlations have been found between daily alcohol intake and corresponding GGT and MCV values, 35 and 34, respectively, in men and 24 and 21 in women. Multiple regression analyses confirm the superiority of GGT over MCV as a laboratory marker of alcohol intake and show the advantage of using them together. A rough estimation of alcohol consumption is proposed as a first step in mass screening of heavy drinkers. (<i>JAMA</i>1981;245:1748-1751)