tbuckley/cabot-search huggingface dataset:
Phase 3 MAGNITUDE study: First results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations.
Authors: Kim N. Chi, Dana E. Rathkopf, Matthew Raymond Smith, Eleni Efstathiou, Gerhardt Attard, David Olmos, Ji Youl Lee, Eric Jay Small, Andrea Juliana Gomes, Guilhem Roubaud, Marniza Saad, Bogdan Zurawski, Valerii Sakalo, Gary Mason, Adam del Corral, George C. Wang, Daphne Wu, Brooke Diorio, Angela Mennicke Lopez- Gitlitz, Shahneen Kaur Sandhu
Journal: Journal of Clinical Oncology (2022)

12 Background: Approximately 20% of mCRPC has alterations in genes associated with HRR and is responsive to PARP inhibitors (PARPi) such as NIRA. Combined PARPi with androgen receptor pathway targeting may also benefit unselected mCRPC. MAGNITUDE assessed whether adding NIRA to AAP improves outcomes in pts with mCRPC with or without alterations in HRR associated genes. Methods: MAGNITUDE (NCT03748641) is a randomized, double-blind phase 3 study. In eligible mCRPC pts, ≤4 mos of prior AAP for mCRPC was allowed. Pts with (HRR biomarker [BM]+; ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2) and without specified gene alterations (HRR BM-) were randomized 1:1 to receive NIRA 200 mg once daily + AAP or placebo (PBO) + AAP. Primary endpoint was radiographic progression-free survival (rPFS) assessed by blinded independent central review (BICR) in the BRCA1/2 group followed by all HRR BM+ pts. Secondary endpoints were time to initiation of cytotoxic chemotherapy (TTCC), time to symptomatic progression (TTSP) and overall survival (OS). Other endpoints included time to PSA progression (TTPP) and objective response rate (ORR). Results: 423 HRR BM+ pts were randomized to NIRA + AAP (n = 212) or PBO + AAP (n = 211). Median age was 69, 23% had prior AAP, 21% had visceral metastases, and 53% had BRCA1/2 mutations. Median follow-up was 18.6 mos. NIRA + AAP significantly improved rPFS by BICR in the BRCA1/2 subgroup and in all HRR BM+ pts, reducing the risk of progression or death by 47% (16.6 vs 10.9 mo) and 27% (16.5 vs 13.7 mo) respectively (Table), vs PBO + AAP. Investigator assessed rPFS was consistent with BICR. NIRA + AAP delayed TTCC, TTSP, and TTPP and improved ORR in HRR BM+ pts (Table). First interim analysis of OS is immature. The preplanned futility analysis in 233 HRR BM- pts showed no benefit of adding NIRA to AAP in the prespecified composite endpoint (first of PSA progression or rPFS; HR, 1.09; 95% CI, 0.75-1.57). No new safety signals were seen. In HRR BM+ pts, 67% and 46.4% had grade 3/4 AEs and 9% and 3.8% discontinued treatment in the NIRA + AAP and PBO + AAP arms, respectively. There were no clinically significant differences in overall quality of life (FACT-P). Conclusions: NIRA + AAP improves rPFS and other clinically relevant outcomes in pts with mCRPC and alterations in HRR associated genes. There was no evidence of benefit with the addition of NIRA to AAP in HRR BM- pts with mCRPC. Clinical trial information: NCT03748641. [Table: see text]
COVID-19 in pregnancy: implications for fetal brain development
Authors: Lydia L. Shook, Elinor L. Sullivan, Jamie O. Lo, Roy H. Perlis, Andrea G. Edlow
Journal: Trends in Molecular Medicine (2022)

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy on the developing fetal brain is poorly understood. Other antenatal infections such as influenza have been associated with adverse neurodevelopmental outcomes in offspring. Although vertical transmission has been rarely observed in SARS-CoV-2 to date, given the potential for profound maternal immune activation (MIA), impact on the developing fetal brain is likely. Here we review evidence that SARS-CoV-2 and other viral infections during pregnancy can result in maternal, placental, and fetal immune activation, and ultimately in offspring neurodevelopmental morbidity. Finally, we highlight the need for cellular models of fetal brain development to better understand potential short- and long-term impacts of maternal SARS-CoV-2 infection on the next generation.
THE WASSERMANN AND PRECIPITATION TESTS
Journal: JAMA (1922)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Patience
Authors: ROBERT RAY MCGEE
Journal: Annals of Internal Medicine (1980)

Ad Libitum1 August 1980PatienceROBERT RAY MCGEE, M.D.ROBERT RAY MCGEE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-93-2-372_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptEighty-three years oldSick all her lifeBuried her mother and fatherWho fretted all their days over the sickly childBuried her husband twenty years agoWorn out with the burden of a sick wifeBuried three childrenDid they worry themselves to deathOver mother?I think she'll bury her doctor, too.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Clarksdale, Mississippi PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1980Volume 93, Issue 2Page: 372-372KeywordsChildren ePublished: 1 December 2008 Issue Published: 1 August 1980 PDF downloadLoading ...
Parkinsonism
Authors: H. G. Garland
Journal: BMJ (1952)

As is true of morbidity in general, we know little of the incidence of Parkinsonism in Great Britain.but with the kind co-operation of a group of practitioners in the Leeds area it has been possible to gain an, approximate idea of it.Incidence of Parkinsonism in Leeds and District Population surveyed 485.903Parkinsonism (all forms) .288Approximate incidence .1 in 1.700 Approximate total in Great Britain .. ..
Intensity of Treatment as Usual and Its Impact on the Effects of Face-to-Face and Internet-Based Psychotherapy for Depression: A Preregistered Meta-Analysis of Randomized Controlled Trials
Authors: Thomas Munder, Alessia Geisshüsler, Tobias Krieger, Johannes Zimmermann, Markus Wolf, Thomas Berger, Birgit Watzke
Journal: Psychotherapy and Psychosomatics (2022)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Treatment as usual (TAU) is the most frequently used control group in randomized trials of psychotherapy for depression. Concerns have been raised that the heterogeneity of treatments in TAU leads to biased estimates of psychotherapy efficacy and to an unclear difference between TAU and control groups like waiting list (WL). &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; We investigated the impact of control group intensity (i.e., amount and degree to which elements of common depression treatments are provided) on the effects of face-to-face and internet-based psychotherapy for depression. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We conducted a preregistered meta-analysis (www.osf.io/4mzyd). We included trials comparing psychotherapy with TAU or WL in patients with symptoms of unipolar depression. Six indicators were used to assess control group intensity. Primary outcome: Standardized mean difference (SMD) of psychotherapy and control in depressive symptoms at treatment termination. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; We included 89 trials randomizing 14,474 patients to 113 psychotherapy conditions and 89 control groups (TAU in 42 trials, WL in 47 trials). Control group intensity predicted trial results in preregistered (one-sided &lt;i&gt;p&lt;/i&gt;s &amp;#x3c; 0.042) and exploratory analyses. Psychotherapy effects were significantly smaller (one-sided &lt;i&gt;p&lt;/i&gt; = 0.002) in trials with higher intensity TAU (SMD = 0.324, CI 0.209 to 0.439) than in trials with lower intensity TAU (SMD = 0.628, CI 0.455 to 0.801). Psychotherapy effects against lower intensity TAU did not differ from effects against WL (two-sided &lt;i&gt;p&lt;/i&gt; = 0.663). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Our results suggest that variation in TAU intensity impacts the outcome of trials. More scrutiny in the design of control groups for clinical trials is recommended.
Manchester Eye Hospital
Authors: J. Windsor
Journal: BMJ (1858)

ABOUT forty cases have been recorded in which a shinin, or glistening appearance of the eye has been observed.I have -he notes of several cases which I had taken before seeing any account of this affection by others.CASE i.The first case of it in my own practice, as far as I remenmber, occurred in a girl namiied Martha Chadwick, aged 18, residing at Cold WVall or Spotlaind Bridge, near Rochidale.She became a patient of the MIanchester Eye Hospital, Novem- '22nd, 1831.For her age, slhe appeared girlish, or younger t.han 18, short, slender, and of pale complexion.She stated that she had had always near, but in other respects pretty good sight, until lately, when her eyes became more liable than before to be affected with slighlt inflammation after ex- posure to cold.About twelve months previously to admission, 'ner left eye faile(d her; it becam-iie rather inflamed and painful; hier visioin with it was less distinct, so that she could no longer readl even large print.She could still see with her right eye till about six weeks before admission, when it also became inflamedl and painful.In about two weeks more, she could onYly just distinguish by it light fiom darkness.When she was adlmitted.both eyes were nearly in the same state as to vision ; still she saidl the liglht, especially of a sunny day, was painful to her.Her eyes were rather prominent; the iris in each was of a greyish colour; the conjunctiva and sclerotic, especially of the riaht eye, were rather injected.The pupils of both eyes were dilated, that of the left circular, that of the liglht somewhat oblong from side to si(le; the left was occupied by a large vbite opaque lens, which projected also against the cornea, occupying a great part of the anterior chamber.In the right eye, a palish amber-coloured but transparent lens projected also through the pupil into the anterior chamber, occup.ing a
Comprehensive genomic profiling unravels molecular targets in patients with metastatic spinal cord compression from prostate cancer.
Authors: Tony Duong, Jue Wang
Journal: Journal of Clinical Oncology (2022)

147 Background: Spinal cord compression (SCC) from prostatic cancer is an oncologic emergency with significant negative impact on morbidity and survival. However, the molecular mechanisms involved in spinal metastases remains largely unclear. The aim of this study was to evaluate the histopathology, molecular profiles, and outcome in these patients. Methods: Twenty patients with magnetic resonance imaging-confirmed metastatic SCC from prostate cancer were identified at Dignity health Cancer Institute. Pathology slides were reviewed and the molecular analysis of 324 cancer-related genes was performed on tumor specimens using targeted next-generation sequencing. Characteristics including age, Gleason score, SCC anatomical site, time to diagnosis of SCC, gene alterations, number of lines of treatment and clinical outcome were analyzed. Results: At the time of diagnosis of SCC, the median age at diagnosis of SCC was 60.5 years old (range=50-76). The median PSA value was 626 ng/ml, 100% of patients have a Gleason score above 7, 30% of patients had visceral metastases. The thoracic spine affecting (15/20) patients is the most common site of SCC. Seventeen patients (75%) were initially treated with surgery combined with radiation therapy (RT), whereas 3 (15%) were managed with RT alone. At the time of this study, 11 patients remain alive (55%), median overall survival (OS) is 20 months, 18 months in treatment naive and 22 months in hormone refractory patients. Molecular analysis revealed gene mutations in all (100%) tumors, The most common gene alterations were PTEN (16%), followed by AR alterations AR (13%), TP53 (11%), TMPRSS2-ERG (8 %), BRCA1/2(4%), RB1(1%) and ATM (1%). Conclusions: Comprehensive genomic profiling revealed several molecular targets in patients with metastatic spinal cord compression from prostate cancer.[Table: see text]
Ribavirin and acute bronchiolitis in infancy.
Authors: A. D. Milner
Journal: BMJ (1988)

this subject, has written: "I remember clearly lying awake on the third night of a disaster and feeling inside me the over- whelming load of grief that was ahead for those people and families we had met at the morgue. . .I felt a terrible sadness and a sense of loss as well as a great burden."3Student nurses and medical students generally receive little training on dealing with death and dying,7 and there is rarely time to visit a mortuary.Social workers, clinical psycholo- gists, and counsellors who may be asked to provide psycho- logical help after a tragedy have usually also had little training for such a task.Training should be improved, but it will never be a substitute for strong support from senior staff.Relatives should thus, it seems, be encouraged to view bodies, and photographs should be kept.But much more research is needed, and reluctance by relatives to see a body should always be respected.
Antibody responses and correlates of protection in the general population after two doses of the ChAdOx1 or BNT162b2 vaccines
Authors: Jia Wei, Koen B. Pouwels, Nicole Stoesser, Philippa C. Matthews, Ian Diamond, Ruth Studley, Emma Rourke, Duncan Cook, John I. Bell, John N. Newton, Jeremy Farrar, Alison Howarth, Brian D. Marsden, Sarah Hoosdally, E. Yvonne Jones, David I. Stuart, Derrick W. Crook, Tim E. A. Peto, A. Sarah Walker, David W. Eyre, Tina Thomas, Daniel Ayoubkhani, Russell Black, Antonio Felton, Megan Crees, Joel Jones, Lina Lloyd, Esther Sutherland, Emma Pritchard, Karina-Doris Vihta, George Doherty, James Kavanagh, Kevin K. Chau, Stephanie B. Hatch, Daniel Ebner, Lucas Martins Ferreira, Thomas Christott, Wanwisa Dejnirattisai, Juthathip Mongkolsapaya, Sarah Cameron, Phoebe Tamblin-Hopper, Magda Wolna, Rachael Brown, Richard Cornall, Gavin Screaton, Katrina Lythgoe, David Bonsall, Tanya Golubchik, Helen Fryer, Stuart Cox, Kevin Paddon, Tim James, Thomas House, Julie Robotham, Paul Birrell, Helena Jordan, Tim Sheppard, Graham Athey, Dan Moody, Leigh Curry, Pamela Brereton, Ian Jarvis, Anna Godsmark, George Morris, Bobby Mallick, Phil Eeles, Jodie Hay, Harper VanSteenhouse, Jessica Lee, Sean White, Tim Evans, Lisa Bloemberg, Katie Allison, Anouska Pandya, Sophie Davis, David I. Conway, Margaret MacLeod, Chris Cunningham
Journal: Nature Medicine (2022)

Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration of protection after a second vaccine dose remain unclear. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 or BNT162b2 vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United Kingdom general population. In 222,493 individuals, we found significant boosting of anti-spike IgG by the second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Older individuals and males had lower peak levels with BNT162b2 but not ChAdOx1, whereas declines were similar across ages and sexes with ChAdOX1 or BNT162b2. Prior infection significantly increased antibody peak level and half-life with both vaccines. Anti-spike IgG levels were associated with protection from infection after vaccination and, to an even greater degree, after prior infection. At least 67% protection against infection was estimated to last for 2-3 months after two ChAdOx1 doses, for 5-8 months after two BNT162b2 doses in those without prior infection and for 1-2 years for those unvaccinated after natural infection. A third booster dose might be needed, prioritized to ChAdOx1 recipients and those more clinically vulnerable.
Characteristics and outcomes of patients managed with surgical resection of brain metastasis from renal cell carcinoma.
Authors: Max Drescher, Sunil H. Patel, Ridwan Alam, Claire De La Calle, Anirudh Yerrapragada, Chetan Bettegowda, Andres Matoso, Yasser Ged, Nirmish Singla
Journal: Journal of Clinical Oncology (2022)

392 Background: For patients with metastatic renal cell carcinoma (mRCC), the presence of brain metastases (BM) confers a poor prognosis compared with alternative metastatic sites. Being an uncommon site of spread, granular data regarding BM in RCC is relatively sparse. We retrospectively reviewed the clinical features and outcomes of patients with surgically-resected BM from mRCC at our institution. Methods: Patients with mRCC and BM were identified within our institutional experience. Clinical and treatment data was obtained from electronic records. A diagnosis of mRCC to the brain was determined by pathological confirmation obtained via metastasectomy or rarely biopsy. Baseline patient demographics, clinicopathological disease characteristics and survival data were extracted. Overall survival (OS) was calculated from the date of BM intervention using Kaplan–Meier methods. Results: 54 patients were identified with surgically resected BM. Median age at RCC diagnosis was 58 years (IQR 49-67) and most patients were male (n = 39, 73%). 30 patients (56%) presented with de novo metastatic disease without any prior localized treatment, and most developed or presented with multiple metastatic sites. The most common histologic subtype was clear cell carcinoma (n = 51, 94%) and high grade disease was common (n = 39, 73%). The initial treatment of BM for the majority of patients was with neurosurgical resection (94%) followed by post-operative stereotactic radiosurgery (SRS) (87%) and systemic therapy (75%). For patients receiving systemic therapy, most received multiple agents (median 2, range 1-5). 32% of patients had received systemic therapy prior to developing BM. 19 patients (35%) received immune-checkpoint inhibitors. The median overall survival for patients from the date of neurosurgical intervention was 14.5 months (95% CI 9.2- 25 months). Conclusions: We present a large institutional series of patients with BM from mRCC treated with surgical resection. While BM remains a poor prognostic factor in mRCC, surgical resection in selected patients remains a viable strategy. Comprehensive molecular profiling of BM and their corresponding primary RCC tumors will shed light on biological tropism of this phenomenon and underscore prognostic and therapeutic implications.[Table: see text]
Infantile gastroenteritis.
Authors: L Haas
Journal: BMJ (1970)

I have never been an enthusiastic advocate of immunofluorescence in the gen- eral diagnosis of virus disease,' but it may encourage those who have struggled to iden- tify virus antigen in smears of inflamed tis- sue or deposits of degenerating cells to know that the identification and titration of specific antibody by straining a known virus antigen is an easier and a much more exact technique.The identification of IgM and other components is a new and significant factor.The man without means to buy a high- speed centrifuge or one without skill in gradient-centrifugation should try fluorescent antibody.I predict that a clean preparation of rubella-infected cells, specific antisera to human immunoglobulins from Wellcome Reagents Ltd., an inexpensive, but efficient Reichert Fluorpan microscope, and patients' sera will provide a rapid, reliable, and beautiful test which will give the ultra-centrifuge a run for its money now, and will replace it quite soon.-Iam, etc.,
The Country Doctor
Authors: G. O. Barber
Journal: BMJ (1951)

was no difficulty in doing what I have described.I did not borrow money, plunge into debt, or live in grinding poverty; I did not separate myself from hospi- tals or abandon their clinical standards; I never sat in a consulting-room twiddling my thumbs; I entered into no cut-throat competition with my medical neighbours; competitors of course we are, to the great advantage of our patients, but there is no cutting of throats, and if there is jealousy or hostility it is marvellous how we disguise it.To judge by behaviour we are friends.I should like here to explode one more myth-namely, that in private practice one must sell one's integrity to any well-to-do patient who covets it.Sooner or later almost everyone doing anything worth doing is offered a price for his or her soul.A medical man is no exception, but he is not in the least bound to accept the offer, which, incidentally, comes at least as often and as persuasively from a public body as from a patient.