tbuckley/cabot-search huggingface dataset:
Costs of Public Health Screening of Children for Presymptomatic Type 1 Diabetes in Bavaria, Germany
Authors: Florian M. Karl, Christiane Winkler, Anette-Gabriele Ziegler, Michael Laxy, Peter Achenbach
Journal: Diabetes Care (2022)

We sought to evaluate costs associated with public health screening for presymptomatic type 1 diabetes in 90,632 children as part of the Fr1da study in Bavaria and in forecasts for standard care.We report on resource use and direct costs for screening-related procedures in the Fr1da study coordination center and laboratory and in participating pediatric practices and local diabetes clinics. Data were obtained from Fr1da study documents, an online survey among pediatricians, and interviews and records of Fr1da staff members. Data were analyzed with tree models that mimic procedures during the screening process. Cost estimates are presented as they were observed in the Fr1da study and as they can be expected in standard care for various scenarios.The costs per child screened in the Fr1da study were €28.17 (95% CI 19.96; 39.63) and the costs per child diagnosed with presymptomatic type 1 diabetes were €9,117 (6,460; 12,827). Assuming a prevalence of presymptomatic type 1 diabetes of 0.31%, as in the Fr1da study, the estimated costs in standard care in Germany would be €21.73 (16.76; 28.19) per screened child and €7,035 (5,426; 9,124) per diagnosed child. Of the projected screening costs, €12.25 would be the costs in the medical practice, €9.34 for coordination and laboratory, and €0.14 for local diabetes clinics.This study provides information for the planning and implementation of screening tests for presymptomatic type 1 diabetes in the general public and for the analysis of the cost-effectiveness of targeted prevention strategies.
Pectus excavatum
Authors: G. H. Wooler, Y. A. S. Mashhour, J. B. Garcia, M. P. Holden, M. I. Ionescu
Journal: Thorax (1969)

The deformity of pectus excavatum is caused by a negative pressure in the anterior mediastinum sucking in the body of the sternum. This is usually due to the heart lying on the left side, leaving the mediastinum empty so that the sternum and costal cartilages are sucked in to fill the empty space. The operation consists of excising the deformed cartilages, mobilizing the sternum, and suturing the pericardial sac into a central position which corrects the deformity.
DISSEMINATED SCLEROSIS
Authors: W. R. Brain
Journal: BMJ (1935)

Disseminated sclerosis is probably due to an infection of the nervous system.Inflammatory patches in which the myelin sheaths of the nerve fibres are destroyed occur mainly in the white matter of the brain and spinal cord, including the optic nerves.These patches appear at intervals, a fresh patch leading to new symptoms or to an exacerbation of existing symptoms, while during the earlier phases of healing and scarring the patient improves, often strikingly.The appearance of patches may be so rapid that the patient dies within three months of the first symptom, or the intervals between the outbreaks may be so long that there is no substantial disablemenL at the end of twenity-five years.The nature of the symp- toms and signs depends upon the situation of the patches in the nervous system.A common early symptom is acute unilateral retrobulbar neuritis, which leads to primary optic atrophy characterized by pallor of the optic disk, especially in its temporal half.The brunt of the damage usually falls upon the pyramidal tracts and the cerebellar connexions.The principal manifesta- tions of the disease therefore are weakness of the upper motor neurone type and-incoordination.These find ex- pression in nystagmus, slurred speech, intention tremor, a spastic and ataxic gait, increased tendon reflexes, and bilateral extensor plantar responses.The abdominal reflexes are usually lost at an early stage.Impaired control over the bladder leading to precipitancy or delay in micturition is a common early symptom.Since the cause of the disease is unknown treatment is necessarily empirical, and it is clearly very difficult to judge the value of any method of treatment for a disorder which runs such a variable course.
Contents
Authors: Alexandra Zauner, Petra Nimmerrichter, Christian Anderwald, Martin Bischof, Mark Schiefermeier, Klaus Ratheiser, Bruno Schneeweiss, Christian Zauner, Christina Aragão, Luana Souza, Adriana Cabanelas, Karen Oliveira, Carmen Pazos-Moura, Walter Zawalich, Kathleen Zawalich, Hanae Yamazaki, Stephen Mitchell, Mary Bollard, Aiqin Zhang, Kwame Osei, Trudy Gaillard, Dara Schuster, Enrica Delfini, Luigi Petramala, Chiara Caliumi, Darlo Cotesta, Giorgio De Toma, Giuseppe Cavallaro, Giuseppe Panzironi, Daniele Diacinti, Savatore Minisola, Emilio D' Erasmo, Gian Mazzuoli, Claudio Letizia, Didier Chapelot, Corinne Marmonier, Paul Valensi, Tetsuo Hayakawa, Toshinari Takamura, Toshio Abe, Shuichi Kaneko
Journal: Metabolism (2006)
Timing of antimicrobial prophylaxis for cesarean section is critical for gut microbiome development in term born infants
Authors: Verena Bossung, Mariia Lupatsii, Lkhagvademberel Dashdorj, Oronzo Tassiello, Sinje Jonassen, Julia Pagel, Martin Demmert, Ellinor Anna Wolf, Achim Rody, Silvio Waschina, Simon Graspeuntner, Jan Rupp, Christoph Härtel
Journal: Gut Microbes (2022)

Animal models imply that the perinatal exposure to antibiotics has a substantial impact on microbiome establishment of the offspring. We aimed to evaluate the effect of timing of antimicrobial prophylaxis for cesarean section before versus after cord clamping on gut microbiome composition of term born infants. We performed an exploratory, single center randomized controlled clinical trial. We included forty pregnant women with elective cesarean section at term. The intervention group received single dose intravenous cefuroxime after cord clamping (n = 19), the control group single dose intravenous cefuroxime 30 minutes before skin incision (n = 21). The primary endpoint was microbiome signature of infants and metabolic prediction in the first days of life as determined in meconium samples by 16S rRNA gene sequencing. Secondary endpoints were microbiome composition at one month and 1 year of life. In meconium samples of the intervention group, the genus Staphylococcus pre-dominated. In the control group, the placental cross-over of cefuroxime was confirmed in cord blood. A higher amino acid and nitrogen metabolism as well as increased abundance of the genera Cutibacterium, Corynebacterium and Streptophyta were noted (indicator families: Cytophagaceae, Lactobacilaceae, Oxalobacteraceae). Predictive models of metabolic function revealed higher 2ʹfucosyllactose utilization in control group samples. In the follow-up visits, a higher abundance of the genus Clostridium was evident in the intervention group. Our exploratory randomized controlled trial suggests that timing of antimicrobial prophylaxis is critical for early microbiome engraftment but not antimicrobial resistance emergence in term born infants.
A phase 2 study of the efficacy and safety of INCMGA00012 in advanced penile squamous cell carcinoma (PSqCC): ORPHEUS.
Authors: Xavier Garcia del Muro, François Riva, M. Andres Cuellar, Pablo Maroto-Rey, Daniel E. Castellano, Patrizia Giannatempo, Miguel Angel A. Climent Duran, Andrea Necchi, Begoña Pérez-Valderrama, Alfonso Gomez De Liano Lista, Carmen Garcias-Espana, Javier Puente, Silverio Ros, Carmen Santander, Cristina Masini, Marta Martínez de Falcon, Almudena Garcia, Miguel Sampayo-Cordero, Andrea Malfettone, David Paez
Journal: Journal of Clinical Oncology (2022)

TPS8 Background: PSqCC is a rare tumor with poor prognosis and limited therapeutic options. The current standard of care for advanced disease has been palliative platinum-based chemotherapy, with only marginal survival benefit. Recent data has shown that the majority of PSqCC patients present high levels of programmed death-ligand 1 (PD-L1). The ORPHEUS trial is evaluating the efficacy and safety of INCMGA00012 –a programmed cell death 1 (PD-1) antagonist– in patients with unresectable, locally advanced or metastatic PSqCC. Methods: ORPHEUS is an international, multicenter, open-label, single-arm, phase 2 clinical trial. Eligible patients are male aged ≥18 years with locally advanced or metastatic PSqCC, ECOG performance status of 0-1, adequate organ function, a life expectancy of ≥12 weeks, and with no prior treatment with PD-1 or PD-L1/2 agents. A total of 18 patients will be enrolled to receive INCMGA00012 500 mg administered intravenously on day 1 of each 28-day cycle. Treatment will continue until progressive disease or unacceptable toxicity. Tumor assessments per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune-related RECIST will be performed approximately every 8 weeks for the first 6 months and every 12 weeks thereafter until progressive disease. The primary endpoint is objective response rate. Secondary objectives include additional efficacy outcomes (clinical benefit rate, progression-free survival (PFS), 6-month PFS, duration of response, time to progression, overall survival, and maximum tumor shrinkage) and safety evaluated as per NCI-CTCAE 5.0. Exploratory objectives will evaluate efficacy based on immune-related RECIST; predictive and prognostic biomarkers; impact of INCMGA00012 on human immunodeficiency virus (HIV) control in patients known to be HIV-positive. The sample size calculation is based on an exact binomial test. At least 4 responders (22.2%) among 18 patients will be adequate to justify further investigation of this strategy. The analyses were designed to attain an 80% power, with a 10% dropout rate assumption, at a nominal one-sided α level of 5%. The response probabilities for null (H0) and alternative hypotheses (H1) were H0: ≤ 5% and H1: ≥ 25%, respectively. All 18 planned patients have been enrolled since the trial began in March 2020. Clinical trial information: NCT04231981.
Auditory Perception
Authors: J. A. M. Martin, D. Martin
Journal: BMJ (1973)

Auditory perceptual tasks involving the discrimination of fine differences in frequency, duration, or rhythmic pattern were given to a group of sixth form schoolboys. The results indicate that there is a wide range of auditory skills for different individuals, even within a relatively homogeneous group. There are also differences in a person9s ability to carry out distinct tasks; there does not necessarily appear to be any correlation between his ability for each task. The findings support observations arising out of consideration of hearing problems in children and adults that pure tone threshold audiometry and its derivatives give an inadequate definition of hearing disorder and a limited understanding of the nature of hearing.
O2 N2 A1.
Journal: JAMA (1895)

It is no longer correct to represent the chemic composition of the atmosphere by the familiar symbols O<sub>2</sub>N<sub>2</sub>—argon, the new element, must be taken into the account, and the formula now is O<sub>2</sub>N<sub>2</sub>A<sub>1</sub>. This era-marking discovery byLord RayleighandProfessor Ramsey, which was fully described in theJournalof Sept. 1, 1894,<sup>1</sup>is the scientific sensation of the day, and although if theHodgkinsfund prize has been awarded to the discoverers, it has escaped observation, they continue to be the recipients of the highest tokens of recognition by learned bodies everywhere. Among the most recent of these tributes is the award toLord Rayleighof theFaradaygold medal by the Chemical Society of London, and of theLeblancmedal toProfessor Ramseyby the Société Chimique de Paris; while it is just announced that " on the recommendation of the National Academy of Science
Pancreatic diagnosis.
Authors: C J Mitchell, E Elias, J E Agnew
Journal: BMJ (1977)

the legs and abdomen.No further outbreaks occurred after the exclusion of fish from the diet.Of questionable significance is the finding of moderate skin-test reactions to fish, shellfish, cheese, milk, grasses, house dust, and dust-mite despite the absence of a history of any atopic reactions in the past at all.
Petechiae and Streptococcal Pharyngitis
Journal: JAMA (1969)

The recent description, in the<i>American Journal of Diseases of Children</i><sup>1</sup>of "dust-like" petechiae associated with streptococcal pharyngitis brings three questions to mind. First, why hasn't the association been made previously? The second and third questions relate to the clinical characteristics and etiology of the lesions, respectively. Although many physicians have claimed to be aware of the association, there is little if anything in the literature to substantiate these claims. The classic description of streptococcosis by Powers and Boisvert<sup>2</sup>and later clinical studies make no mention of petechiae, other than those seen on the palate. The clinical characteristics of these petechiae, their size, color, distribution, and lack of elevation, are unlike the purpura manifest by illness such as meningococcemia. The presence of exudative tonsillitis together with the absence of signs of meningeal irritation mitigate against the diagnosis of meningitis. Although all cases of streptococcal pharyngitis with petechiae will
Genome‐wide meta‐analysis identifies susceptibility loci for autoimmune hepatitis type 1
Authors: You Li, Ying Sun, Yanmin Liu, Bangmao Wang, Jia Li, Hanxiao Wang, Haiping Zhang, Xiaoyi Wang, Xu Han, Qiuxiang Lin, Yang Zhou, Lilin Hu, Yuhu Song, Jie Bao, Ling Gong, Mengying Sun, Xiaoling Yuan, Xinhe Zhang, Min Lian, Xiao Xiao, Qi Miao, Qixia Wang, Ke‐Ke Li, Shiyu Du, Anlin Ma, Yiling Li, Jie Xu, Shanhong Tang, Junping Shi, Yun Xu, Ling Yang, Jiming Zhang, Zuxiong Huang, Lu Zhou, Yong Cui, Michael F. Seldin, M. Eric Gershwin, Huiping Yan, Zhengsheng Zou, Xianbo Zuo, Ruqi Tang, Xiong Ma
Journal: Hepatology (2022)

Abstract Background and Aims Autoimmune hepatitis (AIH) is a rare and chronic autoimmune liver disease. While genetic factors are believed to play a crucial role in the etiopathogenesis of AIH, our understanding of these genetic risk factors is still limited. In this study, we aimed to identify susceptibility loci to further understand the pathogenesis of this disease. Approach and Results We conducted a case–control association study of 1,622 Chinese patients with AIH type 1 and 10,466 population controls from two independent cohorts. A meta‐analysis was performed to ascertain variants associated with AIH type 1. A single‐nucleotide polymorphism within the human leukocyte antigen ( HLA ) region showed the strongest association with AIH (rs6932730: OR = 2.32; p = 9.21 × 10 −73 ). The meta‐analysis also identified two non‐HLA loci significantly associated with AIH: CD28 / CTLA4 / ICOS on 2q33.3 (rs72929257: OR = 1.31; p = 2.92 × 10 −9 ) and SYNPR on 3p14.2 (rs6809477: OR = 1.25; p = 5.48 × 10 −9 ). In silico annotation, reporter gene assays, and CRISPR activation experiments identified a distal enhancer at 2q33.3 that regulated expression of CTLA4 . In addition, variants near STAT1 / STAT4 (rs11889341: OR = 1.24; p = 1.34 × 10 −7 ), LINC00392 (rs9564997: OR = 0.81; p = 2.53 × 10 −7 ), IRF8 (rs11117432: OR = 0.72; p = 6.10 × 10 −6 ), and LILRA4 / LILRA5 (rs11084330: OR = 0.65; p = 5.19 × 10 −6 ) had suggestive association signals with AIH. Conclusions Our study identifies two novel loci ( CD28 / CTLA4 / ICOS and SYNPR ) exceeding genome‐wide significance and suggests four loci as potential risk factors. These findings highlight the importance of costimulatory signaling and neuro‐immune interaction in the pathogenesis of AIH.
Interim results of a phase Ib single-center study of pembrolizumab in combination with chemotherapy in patients with locally advanced or metastatic small cell/neuroendocrine cancers of the prostate and urothelium.
Authors: Arnold I. Chin, Alexandra Drakaki, Sara Rodriguez, Ankush Sachadeva, Margaret Bradley, Nazy Zomorodian, Hanwei Zhang, Shanpeng Li, Gang Li, Matthew Rettig, Sandy Liu
Journal: Journal of Clinical Oncology (2022)

510 Background: Small cell/neuroendocrine cancers irrespective of origin share aggressive phenotypes. Pembrolizumab (MK-3475) is a humanized antibody targeting programmed cell death protein 1 (PD-1) that has shown activity against small cell lung cancers. Preclinical studies showed molecular commonality amongst small cell/neuroendocrine cancers across multiple tissue types. This study evaluated the safety and efficacy signals of pembrolizumab and chemotherapy in patients with small cell/neuroendocrine cancer of the prostate and urothelium. Methods: Patients with locally advanced or metastatic small cell cancer of the bladder or upper urinary tract (cohort 1) and primary small cell or treatment-derived neuroendocrine prostate cancer (NEPC) (cohort 2) received pembrolizumab and standard of care chemotherapy (etoposide and cisplatin/carboplatin for cohorts 1 and 2, with option of docetaxel and carboplatin for cohort 2) with maintenance pembrolizumab for 2 years until unequivocal progressive disease or unacceptable toxicity. The primary endpoint was to estimate ORR and PFS compared to historical controls as well as safety and tolerability. Pretreatment targeted gene mutation sequencing was performed. Results: 14 patients were enrolled (7 cohort 1, 7 cohort 2) with mean age 64.9 (range 53 to 81). ORR across cohorts was 43% (95% CI: (0.17, 0.69)), and 43% (95% CI: (0.06, 0.80)) within each cohort. PFS rate at 12 months (proportion of patients who have not progressed at 12 month) was 61% (95% CI: (0.40,0.95)) across cohorts, 86% (95% CI: (0.63,1.00)) within cohort 1, and 36% (95% CI: (0.12,1.00)) within cohort 2. 3 patients in cohort 1 with locally advanced disease exhibited SD and underwent radical cystectomy, with one patient pT0 and no PD at a mean follow up of 20 months. Grade 3 or higher AEs occurred in 71% of patients, while 29% of patients experienced grade 3 or higher AEs related to pembrolizumab. No patients died or discontinued therapy secondary to adverse treatment effects. In 12 patients where tissue was sufficient, all patients had genomic alterations in either p53 (75%) or Rb (58%). Of the 5 available patients with NEPC, 60% had alternations in DNA damage response genes. Conclusions: In patients with locally advanced or metastatic small cell/neuroendocrine prostate and bladder cancers, combination pembrolizumab with standard of care chemotherapy and maintenance pembrolizumab showed promising efficacy with tolerable adverse events. Clinical trial information: NCT03582475.
Book Listings
Journal: Annals of Internal Medicine (2001)

Book Listings17 April 2001Book ListingsSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-134-8-200104170-00006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail AngiologyVein Diagnosis and Treatment: A Comprehensive ApproachRA Weiss, C Feied, and MA Weiss, eds. 304 pages. New York: McGraw-Hill; 2001. $149.00. ISBN 0070692017. Order phone 800-262-4729.CardiologyAcute Coronary Syndromes2nd edition. EJ Topol, ed. 862 pages. New York: Marcel Dekker; 2001. $100.00. ISBN 0824704169. Order phone 800-228-1160.Angiotensin I Receptor AntagonistsM Epstein and HR Brunner, eds. 384 pages. Philadelphia: Hanley & Belfus; 2001. ISBN 1560534532. Order phone 800-962-1892.Antioxidants and Cardiovascular DiseaseJ Tardif and MG Bourassa, eds. 258 pages. Boston: Kluwer; 2000. $95.00. ISBN 079236564X. Order phone 781-871-1660.Blood Pressure Monitoring in Cardiovascular Medicine and TherapeuticsWB White, ed. 308 ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 April 2001Volume 134, Issue 8Page: B1KeywordsPrevention, policy, and public health ePublished: 17 April 2001 Issue Published: 17 April 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Phase 3 study of first-line treatment with pembrolizumab + belzutifan + lenvatinib or pembrolizumab/quavonlimab + lenvatinib versus pembrolizumab + lenvatinib for advanced renal cell carcinoma (RCC).
Authors: Toni K. Choueiri, Elizabeth R. Plimack, Thomas Powles, Martin H Voss, Howard Gurney, Rachel Kloss Silverman, Rodolfo F. Perini, Karla Rodriguez-Lopez, Brian I. Rini
Journal: Journal of Clinical Oncology (2022)

TPS399 Background: Combination therapy with the PD-1 inhibitor pembrolizumab and the vascular endothelial growth factor (VEGF) inhibitor lenvatinib showed antitumor activity as first-line treatment for advanced clear cell RCC (ccRCC) in the phase 3 KEYNOTE-581/CLEAR study (NCT02811861). Antitumor activity has also been shown with the hypoxia-inducible factor 2α (HIF-2α) inhibitor belzutifan (MK-6482) in ccRCC and with MK-1308A (coformulation of pembrolizumab and the CTLA-4 inhibitor quavonlimab) in non–small cell lung cancer. Therefore, HIF-2α or CTLA-4 inhibition with a PD-1 and VEGF inhibition backbone combination may provide additional benefit as first-line treatment in ccRCC. This open-label, randomized, phase 3 study (NCT04736706) will compare first-line treatment with the novel combination therapies pembrolizumab + belzutifan + lenvatinib (arm A) or MK-1308A + lenvatinib (arm B) with pembrolizumab + lenvatinib (arm C) for advanced RCC. Methods: Approximately 1,431 adults with metastatic ccRCC, measurable disease per RECIST v1.1, and KPS score ≥70% who had not previously undergone systemic therapy for advanced ccRCC will be enrolled. Patients will be randomly assigned 1:1:1 to arm A (belzutifan 120 mg + lenvatinib 20 mg orally once daily [QD] + pembrolizumab 400 mg IV every 6 weeks [Q6W]), arm B (MK-1308A [quavonlimab 25 mg + pembrolizumab 400 mg] IV [Q6W] and lenvatinib 20 mg orally QD), or arm C (pembrolizumab 400 mg IV [Q6W] + lenvatinib 20 mg orally QD). Treatment will continue until documented disease progression, withdrawal of consent, or other discontinuation event; patients will receive pembrolizumab and MK-1308A for up to 18 cycles (̃2 years). Stratification factors are International mRCC Database Consortium (IMDC) score (favorable vs intermediate vs poor), region of the world (North America vs Western Europe vs rest of world), and sarcomatoid features (yes vs no). Response will be assessed by CT or MRI per RECIST v1.1 by blinded independent central review (BICR) at week 12 from randomization, Q6W through week 78, and every 12 weeks thereafter. Adverse events and serious adverse events will be monitored throughout the study and for 90 days after treatment. Dual primary end points are progression-free survival per RECIST v1.1 by BICR and overall survival for arm A or arm B versus arm C in patients with IMDC intermediate/poor status and in all patients regardless of IMDC status. Secondary end points are objective response rate and duration of response per RECIST v1.1 by BICR, patient-reported outcomes, and safety. The study is recruiting patients at sites across, Asia, Australia, Europe, North America, and South America. Clinical trial information: NCT04736706.
Update: Outbreak of Rift Valley Fever—Saudi Arabia, August-November 2000
Journal: JAMA (2000)

On September 10, 2000, the Ministry of Health (MOH), Kingdom of Saudi Arabia and subsequently, the MOH of Yemen began receiving reports of unexplained hemorrhagic fever in humans and associated animal deaths and abortions from the far western Saudi-Yemeni border region. These cases subsequently were confirmed as Rift Valley fever (RVF), the first such cases on the Arabian peninsula. This report updates the findings of the ongoing investigation conducted by the Saudi Arabian MOH in collaboration with CDC and the National Institute of Virology, South Africa.
Dolutegravir dosing for children with HIV weighing less than 20 kg: pharmacokinetic and safety substudies nested in the open-label, multicentre, randomised, non-inferiority ODYSSEY trial
Authors: Hylke Waalewijn, Man K Chan, Pauline D J Bollen, Hilda A Mujuru, Shafic Makumbi, Adeodata R Kekitiinwa, Elizabeth Kaudha, Tatiana Sarfati, Godfrey Musoro, Annet Nanduudu, Abbas Lugemwa, Pauline Amuge, Cecilia L Moore, Pablo Rojo, Carlo Giaquinto, Angela Colbers, Diana M Gibb, Deborah Ford, Anna Turkova, David M Burger
Journal: The Lancet HIV (2022)