scholarly journals Adjuvant rituximab, a potential treatment for the young patient with Graves’ hyperthyroidism (RiGD): study protocol for a single-arm, single-stage, phase II trial

BMJ Open ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. e024705
Author(s):  
Michael Cole ◽  
Ann Marie Hynes ◽  
Denise Howel ◽  
Lesley Hall ◽  
Mario Abinun ◽  
...  

IntroductionGraves’ disease (Graves’ hyperthyroidism) is a challenging condition for the young person and their family. The excess thyroid hormone generated by autoimmune stimulation of the thyroid stimulating hormone receptor on the thyroid gland can have a profound impact on well-being. Managing the young person with Graves’ hyperthyroidism is more difficult than in older people because the side effects of conventional treatment are more significant in this age group and because the disease tends not to resolve spontaneously in the short to medium term. New immunomodulatory agents are available and the anti-B cell monoclonal antibody rituximab is of particular interest because it targets cells that manufacture the antibodies that stimulate the thyroid gland in Graves’.Methods and analysisThe trial aims to establish whether the combination of a single dose of rituximab (500 mg) and a 12-month course of antithyroid drug (usually carbimazole) can result in a meaningful increase in the proportion of patients in remission at 2 years, the primary endpoint. A single-stage, phase II A’Hern design is used. 27 patients aged 12–20 years with newly presenting Graves’ hyperthyroidism will be recruited. Markers of immune function, including lymphocyte numbers and antibody levels (total and specific), will be collected regularly throughout the trial.DiscussionThe trial will determine whether the immunomodulatory medication, rituximab, will facilitate remission above and beyond that observed with antithyroid drug alone. A meaningful increase in the expected proportion of young patients entering remission when managed according to the trial protocol will justify consideration of a phase III trial.Ethics and dissemination The trial has received a favourable ethical opinion (North East - Tyne and Wear South Research Ethics Committee, reference 16/NE/0253, EudraCT number 2016-000209-35). The results of this trial will be distributed at international endocrine meetings, in the peer-reviewed literature and via patient support groups.Trial registration numberISRCTN20381716.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS10126-TPS10126
Author(s):  
Florence Joly Lobbedez ◽  
Laurence Vanlemmens ◽  
Jean-Marc Descotes ◽  
Sophie Abadie-Lacourtoisie ◽  
Claude Boiron ◽  
...  

TPS10126 Background: Fatigue is a frequent side effect with oral targeted therapies (OTT). Physical activity has been reported to improve fatigue and quality of life (QoL). However, few studies focused on metastatic cancer patients and mainly among patients treated with chemotherapy. Furthermore, recent guidelines recommend evaluation and optimization of standardized exercise programs. The aim of our study is to evaluate home-based standard physical exercise program (SPEP) for metastatic cancer patients treated with OTT. Methods: This phase II-III study will randomize (2:1) patients starting first-line OTT for metastatic cancer between an individualized SPEP supervised by a personal coach, and recommended physical exercises via a booklet. Eligible patients will have received ≤2 lines of metastatic chemotherapy, ECOG PS ≤2, controlled pain (VAS < 3/10), and life expectancy ≥3 months. The phase II part (120 patients) will evaluate the feasibility of a 3-month SPEP using the rate of patients performing ≥50% of SPEP (2-stage Fleming: one-sided α = 5%; β = 85%). An interim analysis is planned after the phase II. The phase III will compare the efficacy of an SPEP as opposed to recommendations to reduce fatigue and/or improve physical well-being (PWB) dimensions of QoL (evaluated with FACT-G and FACT-F questionnaires). To show a difference of ≥5 points in PWB and 2.5 for fatigue (α = 2.5%; β = 80%), 312 patients are required in the phase III trial. . Secondary objectives include: PFS, OS, other dimensions of QoL, tolerability and observance of OTT, change in body composition, physical benefits, and a medico-economic study. The SPEP was developed by specialized coaches involved in physical activity and cancer. The study has Ethic committee approval and accrual is planned in 18 French centers in April 2017, for 30 months. This is the first randomized trial dedicated to patients with metastatic cancer treated with OTT evaluating the feasibility and the efficacy of a well design home based SPEP on fatigue and physical well-being.


BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e037090
Author(s):  
Jeanna Parsons Leigh ◽  
Chloe de Grood ◽  
Sofia Ahmed ◽  
Karen Bosma ◽  
Karen E A Burns ◽  
...  

IntroductionWhile the number of women entering medical school now equals or surpasses the number of men, gender equity in medicine has not been achieved. Women continue to be under-represented in leadership roles (eg, deans, medical chairs) and senior faculty positions. In addition, women do not enter medical specialties as often as men, which can have important implications for work environment, reimbursement and the delivery of patient care. Compared with other medical specialties (eg, anaesthesiology, dermatology, etc), critical care medicine is a medical specialty with some of the lowest representation of women. While strategies to improve gender equity in critical care medicine exist in the published literature, efforts to comprehensively synthesise, prioritise and implement solutions have been limited.The objective of this programme of work is to establish priorities for the development and implementation of key strategies to improve the outcomes, well-being and experiences of women in critical care in Canada.Methods and analysisThree phases encompass this programme of work. In phase I, we will catalogue published strategies focused on improving gender inequity across medical specialties through a scoping review. In phase II, we will conduct a modified Delphi consensus process with decision-makers, physicians and researchers to identify key strategies (identified in phase I and proposed by participants in phase II) for improving gender inequity in the specialty of critical care medicine. Finally, in phase III, we will conduct a 1-day stakeholder meeting that engages participants from phase II to build capacity for the development and implementation of top ranked strategies. Data analyses from this programme of work will be both quantitative and qualitative.Ethics and disseminationThe proposed programme of work is a foundational step towards establishing targeted strategies to improve gender inequity in the medical specialty of critical care medicine. Strategies will be prioritised by stakeholders, mapped to preidentified drivers of gender equity in the specialty and be scalable to institutional needs. A final report of our results including the list of top prioritised strategies and implementation objectives will be disseminated to panel participants, critical care leadership teams and major critical care societies who are partners in this work, around the country to facilitate uptake at the local level.The University of Calgary Conjoint Health Research Ethics Board has approved this study (REB16-0890).


2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Seong-Mo Kim ◽  
Sang-Chan Kim ◽  
In-Kwon Chung ◽  
Woo-Hyun Cheon ◽  
Sae-Kwang Ku

Bupleuri Radix (BR), the dried roots ofBupleurum falcatumL., has been used in folk medicine as an antiinflammatory and antioxidative agent. The aqueous extract of BR was evaluated for its possible ameliorative effect in the regulation of hyperthyroidism in l-thyroxine- (LT4-) induced rat model. After oral administration of 300, 150, and 75 mg/kg of BR extracts, once a day for 15 days from 12th LT4 treatments, changes on the body, thyroid gland, liver, and epididymal fat pad weights, serum triiodothyronine, thyroxine, thyroid-stimulating hormone, asparte aminotransferase and alanine aminotransferase concentrations, hepatic lipid peroxidation, glutathione contents, superoxide dismutase, and catalase activities were investigated with thyroid gland, liver, and epididymal fat histopathological changes. The effects of BR extracts were compared with that of propylthiouracil, a standard antithyroid drug 10 mg/kg (intraperitoneally). In this experiment, BR extracts dose dependently reversed LT4-induced hyperthyroidisms, and these effects indicating their potential in the regulation of hyperthyroidism. Further, the BR extract normalized LT4-induced liver oxidative stresses, and also reduced liver and epididymal fat pad changes. BR extracts 150 mg/kg showed comparable effects on the LT4-induced rat hyperthyroidism as compared with PTU 10 mg/kg. These effects of BR may help the improvement of hyperthyroidisms and accompanied various organ damages.


Praxis ◽  
2018 ◽  
Vol 107 (17-18) ◽  
pp. 951-958 ◽  
Author(s):  
Matthias Wilhelm

Zusammenfassung. Herzinsuffizienz ist ein klinisches Syndrom mit unterschiedlichen Ätiologien und Phänotypen. Die überwachte Bewegungstherapie und individuelle körperliche Aktivität ist bei allen Formen eine Klasse-IA-Empfehlung in aktuellen Leitlinien. Eine Bewegungstherapie kann unmittelbar nach Stabilisierung einer akuten Herzinsuffizienz im Spital begonnen werden (Phase I). Sie kann nach Entlassung in einem stationären oder ambulanten Präventions- und Rehabilitationsprogramm fortgesetzt werden (Phase II). Typische Elemente sind Ausdauer-, Kraft- und Atemtraining. Die Kosten werden von der Krankenversicherung für drei bis sechs Monate übernommen. In erfahrenen Zentren können auch Patienten mit implantierten Defibrillatoren oder linksventrikulären Unterstützungssystemen trainieren. Wichtiges Ziel der Phase II ist neben muskulärer Rekonditionierung auch die Steigerung der Gesundheitskompetenz, um die Langzeit-Adhärenz bezüglich körperlicher Aktivität zu verbessern. In Phase III bieten Herzgruppen Unterstützung.


2019 ◽  
Vol 7 (1) ◽  
pp. 9-20
Author(s):  
Inna Yeung

Choice of profession is a social phenomenon that every person has to face in life. Numerous studies convince us that not only the well-being of a person depends on the chosen work, but also his attitude to himself and life in general, therefore, the right and timely professional choice is very important. Research about factors of career self-determination of students of higher education institutions in Ukraine shows that self-determination is an important factor in the socialization of young person, and the factors that determine students' career choices become an actual problem of nowadays. The present study involved full-time and part-time students of Institute of Philology and Mass Communications of Open International University of Human Development "Ukraine" in order to examine the factors of career self-determination of students of higher education institutions (N=189). Diagnostic factors of career self-determination of students studying in the third and fourth year were carried out using the author's questionnaire. Processing of obtained data was carried out using the Excel 2010 program; factorial and comparative analysis were applied. Results of the study showed that initial stage of career self-determination falls down on the third and fourth studying year at the university, when an image of future career and career orientations begin to form. At the same time, the content of career self-determination in this period is contradictory and uncertain, therefore, the implementation of pedagogical support of this process among students is effective.


2021 ◽  
pp. 135245852098863
Author(s):  
Frank Dahlke ◽  
Douglas L Arnold ◽  
Piet Aarden ◽  
Habib Ganjgahi ◽  
Dieter A Häring ◽  
...  

Background: The Oxford Big Data Institute, multiple sclerosis (MS) physicians and Novartis aim to address unresolved questions in MS with a novel comprehensive clinical trial data set. Objective: The objective of this study is to describe the Novartis–Oxford MS (NO.MS) data set and to explore the relationships between age, disease activity and disease worsening across MS phenotypes. Methods: We report key characteristics of NO.MS. We modelled MS lesion formation, relapse frequency, brain volume change and disability worsening cross-sectionally, as a function of patients’ baseline age, using phase III study data (≈8000 patients). Results: NO.MS contains data of ≈35,000 patients (>200,000 brain images from ≈10,000 patients), with >10 years follow-up. (1) Focal disease activity is highest in paediatric patients and decreases with age, (2) brain volume loss is similar across age and phenotypes and (3) the youngest patients have the lowest likelihood (<25%) of disability worsening over 2 years while risk is higher (25%–75%) in older, disabled or progressive MS patients. Young patients benefit most from treatment. Conclusion: NO.MS will illuminate questions related to MS characterisation, progression and prognosis. Age modulates relapse frequency and, thus, the phenotypic presentation of MS. Disease worsening across all phenotypes is mediated by age and appears to some extent be independent from new focal inflammatory activity.


2020 ◽  
pp. 103985622097005
Author(s):  
Oliver Smith ◽  
Jessica Bergmann ◽  
Ulrich Schall

Objective: General practitioners (GPs) are key health professionals for referrals to mental health specialists. Youth mental health issues are particularly challenging, requiring a competent assessment and understanding of appropriate referral pathways. We surveyed local GPs about their understanding of youth mental health problems and needs to competently look after young patients. Methods: GPs working in the Hunter region were contacted via email, fax and post over a 6-month period in 2019. Results: Seventy-five GPs participated. They reported 577 of 1698 (34%) of young people seen 2 weeks prior to being surveyed presented with a mental health problem. Predominantly, referrals were to private practice psychologists and Headspace. Almost a third (31%) reported having limited understanding of ‘at-risk mental state’ and are ‘not always comfortable’ when facing a young person with a mental health problem. Nearly all (95%) expressed interest in attending specialised training. GPs identified treatment costs, scarce access to psychiatrists and limited patient engagement as the main obstacles to help young people. Conclusions: Effective treatment of a mental health problem relies on early identification. GPs are seeing young people on a regular basis but don’t feel well equipped for this task and are keen to up-skill, which needs to be addressed by targeted training.


2021 ◽  
pp. 1-8
Author(s):  
Niamh McGrath ◽  
Colin Patrick Hawkes ◽  
Stephanie Ryan ◽  
Philip Mayne ◽  
Nuala Murphy

Scintigraphy using technetium-99m (<sup>99m</sup>Tc) is the gold standard for imaging the thyroid gland in infants with congenital hypothyroidism (CHT) and is the most reliable method of diagnosing an ectopic thyroid gland. One of the limitations of scintigraphy is the possibility that no uptake is detected despite the presence of thyroid tissue, leading to the spurious diagnosis of athyreosis. Thyroid ultrasound is a useful adjunct to detect thyroid tissue in the absence of <sup>99m</sup>Tc uptake. <b><i>Aims:</i></b> We aimed to describe the incidence of sonographically detectable in situ thyroid glands in infants scintigraphically diagnosed with athyreosis using <sup>99m</sup>Tc and to describe the clinical characteristics and natural history in these infants. <b><i>Methods:</i></b> The newborn screening records of all infants diagnosed with CHT between 2007 and 2016 were reviewed. Those diagnosed with CHT and athyreosis confirmed on scintigraphy were invited to attend a thyroid ultrasound. <b><i>Results:</i></b> Of the 488 infants diagnosed with CHT during the study period, 18/73 (24.6%) infants with absent uptake on scintigraphy had thyroid tissue visualised on ultrasound (3 hypoplastic thyroid glands and 15 eutopic glands). The median serum thyroid-stimulating hormone (TSH) concentration at diagnosis was significantly lower than that in infants with confirmed athyreosis (no gland on ultrasound and no uptake on scintigraphy) (74 vs. 270 mU/L), and median free T4 concentration at diagnosis was higher (11.9 vs. 3.9 pmol/L). Six of 10 (60%) infants with no uptake on scintigraphy but a eutopic gland on ultrasound had transient CHT. <b><i>Conclusion:</i></b> Absent uptake on scintigraphy in infants with CHT does not rule out a eutopic gland, especially in infants with less elevated TSH concentrations. Clinically, adding thyroid ultrasound to the diagnostic evaluation of infants who have athyreosis on scintigraphy may avoid committing some infants with presumed athyreosis to lifelong levothyroxine treatment.


2021 ◽  
Vol 80 (3) ◽  
pp. 567-578 ◽  
Author(s):  
Rosaria Sciarrillo ◽  
Mariana Di Lorenzo ◽  
Salvatore Valiante ◽  
Luigi Rosati ◽  
Maria De Falco

Abstract Different environmental contaminants disturb the thyroid system at many levels. AlkylPhenols (APs), by-products of microbial degradation of AlkylPhenol Polyethoxylates (APEOs), constitute an important class of Endocrine Disrupting Chemicals (EDCs), the two most often used environmental APs being 4-nonylphenol (4-NP) and 4-tert-octylphenol (4-t-OP). The purpose of the present study was to investigate the effects on the thyroid gland of the bioindicator Podarcis siculus of OP alone and in combination with NP. We used radioimmunoassay to determine their effects on plasma 3,3′,5-triiodo-L-thyronine (T3), 3,3′,5,5′-L-thyroxine (T4), thyroid-stimulating hormone (TSH), and thyrotropin-releasing hormone (TRH) levels in adult male lizards. We also investigated the impacts of AP treatments on hepatic 5′ORD (type II) deiodinase and hepatic content of T3 and T4. After OP and OP + NP administration, TRH levels increased, whereas TSH, T3, and T4 levels decreased. Lizards treated with OP and OP + NP had a higher concentration of T3 in the liver and 5′ORD (type II) activity, whereas T4 concentrations were lower than that observed in the control group. Moreover, histological examination showed that the volume of the thyroid follicles became smaller in treated lizards suggesting that that thyroid follicular epithelial cells were not functionally active following treatment. This data collectively suggest a severe interference with hypothalamus–pituitary–thyroid axis and a systemic imbalance of thyroid hormones. Graphic Abstract


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1464.1-1465
Author(s):  
J. Blaess ◽  
J. Walther ◽  
J. E. Gottenberg ◽  
J. Sibilia ◽  
L. Arnaud ◽  
...  

Background:Rheumatoid arthritis (RA) is the most frequent chronic inflammatory diseases with an incidence of 0.5% to 1%. Therapeutic arsenal of RA has continuously expanded in recent years with the recent therapeutic progress with the arrival of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), biological (bDMARDs) and targeted synthetic (tsDMARDs), JAK inhibitors. However, there are still some unmet needs for patients who do not achieve remission and who continue to worsen despite treatments. Of note, only approximately 40% of patients are ACR70 responders, in most randomized controlled trials. For these patients, finding new therapeutic avenues is challenging.Objectives:The objective of our study was to analyze the whole pipeline of immunosuppressive and immunomodulating drugs evaluated in RA and describe their mechanisms of action and stage of clinical development.Methods:We conducted a systematic review of all drug therapies in clinical development in RA in 17 databases of international clinical trials. Inclusion criterion: study from one of the databases using the keywords “Rheumatoid arthritis” (search date: June 1, 2019). Exclusion criteria: non-drug trials, trials not related to RA or duplicates. We also excluded dietary regimen or supplementations, cellular therapies, NSAIDs, glucorticoids or their derivatives and non-immunosuppressive or non-immunomodulating drugs. For each csDMARD, bDMARD and tsDMARD, we considered the study at the most advanced stage. For bDMARDs, we did not take into account biosimilars.Results:The research identified 4652 trials, of which 242 for 243 molecules met the inclusion and exclusion criteria. The developed molecules belong to csDMARDs (n=21), bDMARDs (n=117), tsDMARDs (n=105).Among the 21 csDMARDs molecules: 8 (38%) has been withdrawn, 4 (19%) are already labelled in RA (hydroxychloroquine, leflunomide, methotrexate and sulfasalazine) and 9 (43%) are in development: 1 (11%) is in phase I/II, 5 (56%) in phase II, 3 (33%) in phase IV.Among the 117 bDMARDs molecules: 69 (59%) has been withdrawn, 9 (8%) are labeled in RA (abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, sarilumab, tocilizumab) and 39 (33%) are in development: 9 (23%) in phase I, 3 (8%) in phase I/II, 21 (54%) in phase II, 5 (12%) are in phase III, 1 (3%) in phase IV. bDMARDs currently under development target B cells (n=4), T cells (n=2), T/B cells costimulation (n=2),TNF alpha (n=2), Interleukine 1 or his receptor (n=3), Interleukine 6 or his receptor (n=7), Interleukine 17 (n=4), Interleukine 23 (n=1), GM-CSF (n=1), other cytokines or chemokines (n=5), integrins or adhesion proteins (n=3), interferon receptor (n=1) and various other targets (n=4).Among the 105 tsDMARDs molecules: 64 (61%) has been withdrawn, 6 (6%) JAK inhibitors, have just been or will probably soon be labelled (baricitinib, filgotinib, peficitinib, tofacitinib and upadacitinib), 35 (33%) are in development: 8 (24%) in phase I, 26 (74%) in phase II, 1 (3%) in phase III and. tsDMARDs currently under development target tyrosine kinase (n=12), janus kinase (JAK) (n=3), sphingosine phostate (n=3), PI3K pathway (n=1), phosphodiesterase-4 (n=3) B cells signaling pathways (n=3) and various other targets (n=10).Conclusion:A total of 242 therapeutic trials involving 243 molecules have been or are being evaluated in RA. This development does not always lead to new treatments since 141 (58%) have already been withdrawn. Hopefully, some of the currently evaluated drugs will contribute to improve the therapeutic management of RA patients, requiring a greater personalization of therapeutic strategies, both in the choice of molecules and their place in therapeutic sequences.Disclosure of Interests:Julien Blaess: None declared, Julia Walther: None declared, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Jean Sibilia: None declared, Laurent Arnaud: None declared, Renaud FELTEN: None declared


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