DOCSLIB.ORG

Clinical Reference Group SBAR: Therapies for COVID-19

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Clinical Reference Group SBAR: Therapies for COVID-19 Clinical Reference Group SBAR: Therapies for COVID-19 UPDATED: September 8th, 2021 The British Columbia COVID-19 Therapeutics Committee (CTC) meets bi-weekly to discuss the most current research on the use of therapies in the management of COVID-19. Situation SARS-CoV-2 (previously named 2019-nCoV), the virus that causes the clinical illness COVID-19, is a novel RNA virus belonging to the coronavirus family. With over 221 million cases worldwide, various treatments are being used clinically or undergoing evaluation. In preparation for in-patient treatment of COVID-19 at BC’s health care facilities, the COVID Therapeutics Committee has reviewed the evidence for these therapies and made recommendations concerning their use in consultation with various groups such as Infectious Diseases, Medical Microbiology, Intensive Care, Internal Medicine, Emergency Medicine, Hospitalists, Long Term Care and Pharmacy. The COVID Therapeutics Committee has also provided general treatment guidelines for anti-infective use in the setting of viral pneumonia for in- patients. As this is an evolving situation, we are making the necessary amendments to this SBAR along with up-to-date recommendations weekly, and as emerging information becomes available. Background Coronaviruses (CoV) are a large family of viruses that cause illness ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV-1). SARS-CoV-2, the virus responsible for the COVID-19 pandemic, is a non-segmented, positive sense RNA virus most closely related to SARS-CoV-1, with 82% nucleotide identity. There have been over 221 million cases of COVID-19 to date, with a global case fatality rate of ranging between 2% to 10% depending on the country and criteria for testing. Remdesivir is currently the only antiviral agent conditionally approved in Canada for treatment of COVID-19. Certain immunomodulatory treatments have been studied and shown positive results, for example corticosteroids and IL-6 inhibitors such as tocilizumab, while others continue to be investigated in clinical trials. Concomitantly, several well-designed studies have shown various therapies to have no effect or pose safety concerns. Agents of particular interest currently include monoclonal antibodies against the spike protein, as well as oral direct acting antivirals currently in the development pipeline. The most significant advancement in COVID-19 therapeutics is dexamethasone and tocilizumab, with survival benefit, followed by data surrounding anticoagulation for hospitalized patients. While less impactful, colchicine, inhaled budesonide and remdesivir have been shown to decrease time to recovery or improve symptoms in a variety of patient populations. As of January 16, 2021, the Cochrane COVID-19 Study Register lists over 4300 interventional trials. A large proportion of the discussion regarding potential treatment for COVID-19 within the medical community has been occurring through non-academic channels such as social media, blogs or the news. A scientific literature search of potential non-vaccine therapies for COVID-19 and other coronaviruses (search strategy below) resulted in over hundreds of publications. The following pharmaceutical agents are discussed in detail below (see “Assessment”): 1. corticosteroids 2. tocilizumab, sarilumab 3. therapeutic anticoagulation and venous thromboembolism (VTE) prophylaxis 4. colchicine 5. remdesivir# 6. lopinavir/ritonavir (Kaletra®) 7. chloroquine or hydroxychloroquine 8. oseltamivir 9. ribavirin and interferon 10. ivermectin# 11. ascorbic acid and vitamin D 12. biologics/small molecules (anakinra, baricitinib, ruxolitinib) # 13. convalescent plasma#, intravenous immunoglobulin (IVIG) and monoclonal antibodies/antibody cocktails 14. antibiotics 15. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) 16. Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs) 17. SSRIs # Denotes that a clinical trial of named therapy is currently planned or underway in British Columbia. Links below for registered trials in Canada and British Columbia. Canada: https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-clinical- trials/list-authorized-trials.html British Columbia: https://bcahsn.ca/covid-19-response/inventory/ Articles commenting on safety of other agents, for example Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blockers (ARBs), in the context of COVID-19 have also been published. These topics are also discussed in detail below (see “Assessment”). Other investigational therapies that have been suggested by various medical and non-medical literature sources include ASC09, azvudine, baloxavir marboxil/favipiravir, camostat mesylate, darunavir/cobicistat, camrelizumab,niacin, thymosin, natural health products and traditional Chinese medicines. Information on these therapies are limited due to lack of data, lack of availability, or both. Detailed assessment on these therapies will be provided when credible scientific literature becomes available. Page 2 of 112 It is recognized that there may be extenuating clinical circumstances where clinicians decide to use unproven therapies when clinical trials are unavailable. In those circumstances where unproven therapies are used, the WHO has provided a standardized case record form for data collection to ensure that there is contribution to scientific research and the clinical community. Locally, in British Columbia, there is consensus between expert groups regarding treatment of COVID-19 with both unproven therapies and therapies shown to be efficacious in clinical trials through the BCCDC’s Clinical Reference Group, Provincial Antimicrobial Committee of Experts (PACE), and the clinical community. The agreement is that investigational treatments will not be used outside of approved randomized controlled trials (RCTs). This also applies to specific patients like those with immunocompromising conditions (e.g. solid organ transplant). Many BC Health Authorities have committed to enrolling in RCTs such as the CATCO study which aims to investigate the use of remdesivir in the treatment of COVID-19 in hospitalized patients. This RCT is led by Dr. Srinivas Murthy (Infectious Diseases and Critical Care) from BC Children’s Hospital and funded through the Canadian Institutes of Health Research. Several other trials are in the process of recruiting sites across Canada and are in various stages of ethics and operational approval. The BC Health Authorities are currently reviewing the local feasibility of these clinical studies on a regular basis. For recommendations pertaining to Multisystem Inflammatory Syndrome in Children (MIS-C) and COVID-19 please visit BCCDC website at: http://www.bccdc.ca/Health-Professionals- Site/Documents/COVID19_MIS-C_ClinicianGuidance.pdf For recommendations pertaining to Multisystem Inflammatory Syndrome in Adults (MIS-A) and COVID- 19 please visit BCCDC website at: https://www.cmaj.ca/content/193/25/E956 Page 3 of 112 Assessment Corticosteroids Recommendation: i) Non hospitalized patients with no oxygen requirements: In adults with mildly ill COVID-19 aged 65 and over OR aged 50 and over with underlying health conditions and within 14 days of symptom onset, inhaled budesonide 800 μg twice daily for 14 days may be considered on a case by case basis in discussion with the patient by clearly highlighting the uncertainty in the benefit of treatment, and the risks and potential adverse effects. Informed consent should be obtained and treatment initiated as soon as possible. Underlying health conditions include weakened immune system due to illness or medication; heart disease and/or hypertension; chronic lung disease; diabetes; hepatic impairment; stroke or other neurological condition; obesity or BMI above 35. ii) Hospitalized patients requiring oxygen or higher levels of respiratory support Dexamethasone 6 mg IV/PO q24h for up to 10 days is strongly recommended (RECOVERY trial), unless higher doses are clinically indicated (e.g. asthma exacerbation, refractory septic shock, history of chronic steroid use, obstetric use for fetal lung maturation). Hydrocortisone 50 mg IV q6h is recommended as an alternative (REMAP-CAP trial). If dexamethasone and hydrocortisone are not available, methylprednisolone 32 mg IV q24h or prednisone 40 mg PO daily are recommended. Inhaled budesonide Use of inhaled budesonide was prompted by the noticeable decrease in COVID-19 symptoms in patients with chronic obstructive pulmonary disease. Two trials assessed whether inhaled steroids decreased hospitalization. While both trials are limited by their design and one was stopped early because of enrollment, both demonstrated improvement in self-reported symptom duration, albeit small and not seen with more objective measures. Furthermore, the decrease in hospitalization or medical related visits remains unclear. Study details: STOIC: inhaled budesonide in the treatment of early COVID-19 ● Design: Open-label, parallel-group, phase 2, RCT ● Inclusion: Adults aged older than 18 years with symptoms of COVID-19 (new onset cough and fever or anosmia, or both) within 7 days ● Exclusion: recent use (within 7 days) of inhaled or systemic glucocorticoids or if they had a known allergy or contraindication to inhaled budesonide ● Intervention: usual care or intervention with budesonide dry powder inhaler (Pulmicort Turbuhaler, AstraZeneca,
Load more

Recommended publications
  • Extended-Release 30 Mcg Capsules Service Request Form Fax: 1-844-660-7083 | Phone: 1-844-414-Opko (6756) E-Mail: [email protected]
    RAYALDEE® (CALCIFEDIOL) EXTENDED-RELEASE 30 MCG CAPSULES SERVICE REQUEST FORM FAX: 1-844-660-7083 | PHONE: 1-844-414-OPKO (6756) E-MAIL: [email protected] 1. Patient Information Please complete all fields to prevent any delays. New start to Rayaldee® therapy Existing patient on therapy E-mail Address: Preferred Method of Contact: Cell Phone Home Phone Email Text First Name Last Name SS # (Last 4 only) Preferred Time of Contact: Morning Afternoon Evening Male Female Ok to leave a message: Yes No Date of Birth (MM/DD/YYYY) Primary Language: English Spanish Other:________________________________ 2. Patient Insurance Information Address Attached is a copy of both sides of the patient's insurance card City State ZIP Primary Insurance Phone # Cell Phone Home Phone Policy Holder Name Relationship to Patient Alternate Contact or Healthcare Proxy First Name, Last Name and Phone Insurance ID # Group # 3. Patient Clinical Information Please include supporting clinical documentation. ● ICD-10 Code: ● Lab Values & dates: Please check box 1. or 2. below 25(OH)D__________|__________ Calcium__________|__________ (N18.3) CKD stage 3, (N25.81) Secondary hyperparathyroidism, and 1. value date value date (E55.9) Vitamin D deficiency 2. (N18.4) CKD stage 4, (N25.81) Secondary hyperparathyroidism, and (E55.9) Vitamin D deficiency ● Therapies within the previous 6 months: No previous therapies Hectorol® (doxercalciferol) Rocaltrol® (calcitriol) OTC Vitamin D2 ® OTC Vitamin D3 Prescription Vitamin D2 (ergocalciferol) Zemplar (paricalcitol) 4. Prescriber Information Specialty of Prescriber: Nephrologist PCP Endocrinologist Internist First Name Last Name Phone Fax Practice Name Oce Contact Preferred Time of Contact Address NPI # City State ZIP 5.
    [Show full text]
  • A Clinical Update on Vitamin D Deficiency and Secondary
    References 1. Mehrotra R, Kermah D, Budoff M, et al. Hypovitaminosis D in chronic 17. Ennis JL, Worcester EM, Coe FL, Sprague SM. Current recommended 32. Thimachai P, Supasyndh O, Chaiprasert A, Satirapoj B. Efficacy of High 38. Kramer H, Berns JS, Choi MJ, et al. 25-Hydroxyvitamin D testing and kidney disease. Clin J Am Soc Nephrol. 2008;3:1144-1151. 25-hydroxyvitamin D targets for chronic kidney disease management vs. Conventional Ergocalciferol Dose for Increasing 25-Hydroxyvitamin supplementation in CKD: an NKF-KDOQI controversies report. Am J may be too low. J Nephrol. 2016;29:63-70. D and Suppressing Parathyroid Hormone Levels in Stage III-IV CKD Kidney Dis. 2014;64:499-509. 2. Hollick MF. Vitamin D: importance in the prevention of cancers, type 1 with Vitamin D Deficiency/Insufficiency: A Randomized Controlled Trial. diabetes, heart disease, and osteoporosis. Am J Clin Nutr 18. OPKO. OPKO diagnostics point-of-care system. Available at: http:// J Med Assoc Thai. 2015;98:643-648. 39. Jetter A, Egli A, Dawson-Hughes B, et al. Pharmacokinetics of oral 2004;79:362-371. www.opko.com/products/point-of-care-diagnostics/. Accessed vitamin D(3) and calcifediol. Bone. 2014;59:14-19. September 2 2015. 33. Kovesdy CP, Lu JL, Malakauskas SM, et al. Paricalcitol versus 3. Giovannucci E, Liu Y, Rimm EB, et al. Prospective study of predictors ergocalciferol for secondary hyperparathyroidism in CKD stages 3 and 40. Petkovich M, Melnick J, White J, et al. Modified-release oral calcifediol of vitamin D status and cancer incidence and mortality in men.
    [Show full text]
  • Changes in Serum Micrornas After Anti-IL-5 Biological Treatment of Severe Asthma
    International Journal of Molecular Sciences Article Changes in Serum MicroRNAs after Anti-IL-5 Biological Treatment of Severe Asthma Manuel J. Rial 1,2, José A. Cañas 2,3 , José M. Rodrigo-Muñoz 2,3 , Marcela Valverde-Monge 1 , Beatriz Sastre 2,3 , Joaquín Sastre 1,3 and Victoria del Pozo 2,3,* 1 Allergy Unit, Hospital Universitario Fundación Jiménez Díaz, 28040 Madrid, Spain; [email protected] (M.J.R.); [email protected] (M.V.-M.); [email protected] (J.S.) 2 Department of Immunology, IIS-Fundación Jiménez Díaz, 28040 Madrid, Spain; [email protected] (J.A.C.); [email protected] (J.M.R.-M.); [email protected] (B.S.) 3 CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain * Correspondence: [email protected]; Tel.: +34-9155-048-91 Abstract: There is currently enough evidence to think that miRNAs play a role in several key points in asthma, including diagnosis, severity of the disease, and response to treatment. Cells release different types of lipid double-membrane vesicles into the extracellular microenvironment, including exosomes, which function as very important elements in intercellular communication. They are capable of distributing genetic material, mRNA, mitochondrial DNA, and microRNAs (miRNAs). Serum miRNA screening was performed in order to analyze possible changes in serum miRNAs in 10 patients treated with reslizumab and 6 patients with mepolizumab after 8 weeks of treatment. The expression of miR-338-3p was altered after treatment (p < 0.05), although no significant differences between reslizumab and mepolizumab were found. Bioinformatic analysis showed that miR-338-3p regulates important pathways in asthma, such as the MAPK and TGF-β signaling pathways and the Citation: Rial, M.J.; Cañas, J.A.; biosynthesis/degradation of glucans (p < 0.05).
    [Show full text]
  • MEP-AST Mepolizumab Versus Placebo for Asthma
    MEP-AST Mepolizumab versus placebo for asthma Mepolizumab versus placebo for asthma Review information Review type: Intervention Review number: MEP-AST Authors Colin Powell1, Stephen J Milan2, Kerry Dwan3, Lynne Bax4, Nicola Walters5 1Department of Child Health, Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine, Cardiff, UK 2Lancaster Health Hub, Lancaster University, Lancaster, UK 3Department of Biostatistics, University of Liverpool, Liverpool, UK 4Lancashire Care NHS Foundation Trust, Preston, UK 5Chest Unit, St George's University Hospitals NHS Foundation Trust, London, UK Citation example: Powell C, Milan SJ, Dwan K, Bax L, Walters N. Mepolizumab versus placebo for asthma. Cochrane Database of Systematic Reviews 2015 , Issue 7 . Art. No.: CD010834. DOI: 10.1002/14651858.CD010834.pub2 . Contact person Colin Powell Senior Lecturer Department of Child Health Institute of Molecular and Experimental Medicine, Cardiff University School of Medicine Cardiff UK E-mail: [email protected] Dates Assessed as Up-to-date:19 November 2014 Date of Search: 19 November 2014 Next Stage Expected: 6 June 2017 Protocol First Published:Issue 11 , 2013 Review First Published: Issue 7 , 2015 Last Citation Issue: Issue 7 , 2015 What's new Date Event Description History Date Event Description Abstract Background Mepolizumab is a human monoclonal antibody against interleukin-5 (IL-5), the main cytokine involved in the activation of eosinophils, which in turn causes airway inflammation. Recent studies have suggested these agents may have a role in reducing exacerbations and improving health-related quality of life (HRQoL). There are no recommendations for the use of mepolizumab in adults or children in the recent update of the BTS/SIGN guidelines (BTS/SIGN 2014).
    [Show full text]
  • Simulation of Physicochemical and Pharmacokinetic Properties of Vitamin D3 and Its Natural Derivatives
    pharmaceuticals Article Simulation of Physicochemical and Pharmacokinetic Properties of Vitamin D3 and Its Natural Derivatives Subrata Deb * , Anthony Allen Reeves and Suki Lafortune Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, Miami, FL 33169, USA; [email protected] (A.A.R.); [email protected] (S.L.) * Correspondence: [email protected] or [email protected]; Tel.: +1-224-310-7870 or +1-305-760-7479 Received: 9 June 2020; Accepted: 20 July 2020; Published: 23 July 2020 Abstract: Vitamin D3 is an endogenous fat-soluble secosteroid, either biosynthesized in human skin or absorbed from diet and health supplements. Multiple hydroxylation reactions in several tissues including liver and small intestine produce different forms of vitamin D3. Low serum vitamin D levels is a global problem which may origin from differential absorption following supplementation. The objective of the present study was to estimate the physicochemical properties, metabolism, transport and pharmacokinetic behavior of vitamin D3 derivatives following oral ingestion. GastroPlus software, which is an in silico mechanistically-constructed simulation tool, was used to simulate the physicochemical and pharmacokinetic behavior for twelve vitamin D3 derivatives. The Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) Predictor and PKPlus modules were employed to derive the relevant parameters from the structural features of the compounds. The majority of the vitamin D3 derivatives are lipophilic (log P values > 5) with poor water solubility which are reflected in the poor predicted bioavailability. The fraction absorbed values for the vitamin D3 derivatives were low except for calcitroic acid, 1,23S,25-trihydroxy-24-oxo-vitamin D3, and (23S,25R)-1,25-dihydroxyvitamin D3-26,23-lactone each being greater than 90% fraction absorbed.
    [Show full text]
  • Asthma Agents
    APPROVED PA Criteria Initial Approval Date: July 10, 2019 Revised Date: January 20, 2021 CRITERIA FOR PRIOR AUTHORIZATION Asthma Agents BILLING CODE TYPE For drug coverage and provider type information, see the KMAP Reference Codes webpage. MANUAL GUIDELINES Prior authorization will be required for all current and future dose forms available. All medication-specific criteria, including drug-specific indication, age, and dose for each agent is defined in Table 1 below. Benralizumab (Fasenra®) Dupilumab (Dupixent®) Mepolizumab (Nucala®) Omalizumab (Xolair®) Reslizumab (Cinqair®) GENERAL CRITERIA FOR INITIAL PRIOR AUTHORIZATION: (must meet all of the following) • Must be approved for the indication, age, and not exceed dosing limits listed in Table 1. • Must be prescribed by or in consultation with a pulmonologist, allergist, or immunologist.1,2 • For all agents listed, the preferred PDL drug, which treats the PA indication, is required unless the patient meets the non-preferred PDL PA criteria. • Must have experienced ≥ 2 exacerbations within the last 12 months despite meeting all of the following (exacerbation is defined as requiring the use of oral/systemic corticosteroids, urgent care/hospital admission, or intubation: o Patient adherence to two long-term controller medications, including a high-dose inhaled corticosteroid 1,2 (ICS) and a long-acting beta2-agonist (LABA) listed in Table 2. ▪ Combination ICS/LABA and ICS/LABA/LAMA products meet the requirement of two controller medications. o Patient must have had an adequate trial (at least 90 consecutive days) of a leukotriene modifier or a long-acting muscarinic antagonist (LAMA) as a third long-term controller medication listed in Table 2.
    [Show full text]
  • Inadequate Assessment of Adherence To€Maintenance Medication Leads
    ORIGINAL ARTICLE ASTHMA Inadequate assessment of adherence to maintenance medication leads to loss of power and increased costs in trials of severe asthma therapy: results from a systematic literature review and modelling study Matshediso C. Mokoka1, Melissa J. McDonnell2, Elaine MacHale1, Breda Cushen1, Fiona Boland3, Sarah Cormican2, Christina Doherty4, Frank Doyle 5, Richard W. Costello6 and Garrett Greene1 @ERSpublications Trials of add-on therapy for severe asthma do not include adequate assessment of adherence to maintenance therapy. As a result, they suffer from a significant loss of statistical power, leading to greatly increased sample sizes and associated costs. http://ow.ly/ZCyH30nSFHc Cite this article as: Mokoka MC, McDonnell MJ, MacHale E, et al. Inadequate assessment of adherence to maintenance medication leads to loss of power and increased costs in trials of severe asthma therapy: results from a systematic literature review and modelling study. Eur Respir J 2019; 53: 1802161 [https://doi. org/10.1183/13993003.02161-2018]. ABSTRACT Adherence to inhaled maintenance therapy in severe asthma is rarely adequately assessed, and its influence on trial outcomes is unknown. We systematically determined how adherence to maintenance therapy is assessed in clinical trials of “add-on” therapy for severe asthma. We model the improvement in trial power that could be achieved by accurately assessing adherence. A systematic search of six major databases identified randomised trials of add-on therapy for severe asthma. The relationship between measuring adherence and study outcomes was assessed. An estimate of potential improvements in statistical power and sample size was derived using digitally recorded adherence trial data.
    [Show full text]
  • Dietary Supplements Compendium Volume 1
    2015 Dietary Supplements Compendium DSC Volume 1 General Notices and Requirements USP–NF General Chapters USP–NF Dietary Supplement Monographs USP–NF Excipient Monographs FCC General Provisions FCC Monographs FCC Identity Standards FCC Appendices Reagents, Indicators, and Solutions Reference Tables DSC217M_DSCVol1_Title_2015-01_V3.indd 1 2/2/15 12:18 PM 2 Notice and Warning Concerning U.S. Patent or Trademark Rights The inclusion in the USP Dietary Supplements Compendium of a monograph on any dietary supplement in respect to which patent or trademark rights may exist shall not be deemed, and is not intended as, a grant of, or authority to exercise, any right or privilege protected by such patent or trademark. All such rights and privileges are vested in the patent or trademark owner, and no other person may exercise the same without express permission, authority, or license secured from such patent or trademark owner. Concerning Use of the USP Dietary Supplements Compendium Attention is called to the fact that USP Dietary Supplements Compendium text is fully copyrighted. Authors and others wishing to use portions of the text should request permission to do so from the Legal Department of the United States Pharmacopeial Convention. Copyright © 2015 The United States Pharmacopeial Convention ISBN: 978-1-936424-41-2 12601 Twinbrook Parkway, Rockville, MD 20852 All rights reserved. DSC Contents iii Contents USP Dietary Supplements Compendium Volume 1 Volume 2 Members . v. Preface . v Mission and Preface . 1 Dietary Supplements Admission Evaluations . 1. General Notices and Requirements . 9 USP Dietary Supplement Verification Program . .205 USP–NF General Chapters . 25 Dietary Supplements Regulatory USP–NF Dietary Supplement Monographs .
    [Show full text]
  • Mathematical Analysis of Córdoba Calcifediol Trial Suggests
    medRxiv preprint doi: https://doi.org/10.1101/2020.11.08.20222638; this version posted December 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Mathematical analysis of Córdoba calcifediol trial suggests strong role for Vitamin D in reducing ICU admissions of hospitalized COVID-19 patients 1,2* 1,2 Irwin Jungreis ​ and Manolis Kellis ​ ​ 1 MIT​ Computer Science and Artificial Intelligence Laboratory, Cambridge, MA 2 Broad​ Institute of MIT and Harvard, Cambridge, MA * Corresponding​ author: [email protected] ​ Abstract A randomized controlled trial of calcifediol (25-hydroxyvitamin D3) as a treatment for hospitalized COVID-19 ​ ​ patients in Córdoba, Spain, found that the treatment was associated with reduced ICU admissions with very large effect size and high statistical significance, but the study has had limited impact because it had only 76 patients and imperfect blinding, and did not measure vitamin D levels pre- and post-treatment or adjust for several comorbidities. Here we reanalyze the reported results of the study using rigorous and well established statistical techniques, and find that the randomization, large effect size, and high statistical significance address many of these concerns. We show that random assignment of patients to treatment and control groups is highly unlikely to distribute comorbidities or other prognostic indicators sufficiently unevenly to account for the large effect size. We also show that imperfect blinding would need to have had an implausibly large effect to account for the reported results.
    [Show full text]
  • WO 2016/176089 Al 3 November 2016 (03.11.2016) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/176089 Al 3 November 2016 (03.11.2016) P O P C T (51) International Patent Classification: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A01N 43/00 (2006.01) A61K 31/33 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (21) International Application Number: KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, PCT/US2016/028383 MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (22) International Filing Date: PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, 20 April 2016 (20.04.2016) SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, 62/154,426 29 April 2015 (29.04.2015) US TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, (71) Applicant: KARDIATONOS, INC. [US/US]; 4909 DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, Lapeer Road, Metamora, Michigan 48455 (US).
    [Show full text]
  • Dupixent (Dupilumab) Fasenra (Benralizumab) Nucala (Mepolizumab) Xolair (Omalizumab) Effective January 1, 2021
    Asthma and Allergy Injectables Cinqair (reslizumab) Dupixent (dupilumab) Fasenra (benralizumab) Nucala (mepolizumab) Xolair (omalizumab) Effective January 1, 2021 ☐ MassHealth Plan ☒ ☒Commercial/Exchange Prior Authorization Program Type ☐ Quantity Limit ☒ Pharmacy Benefit Benefit ☐ Step Therapy ☒ Medical Benefit (NLX) Specialty This medication has been designated specialty and must be filled at a contracted Limitations specialty pharmacy when obtained through the pharmacy benefit. Specialty Medications All Plans Phone: 866-814-5506 Fax: 866-249-6155 Non-Specialty Medications Contact MassHealth Phone: 877-433-7643 Fax: 866-255-7569 Information Commercial Phone: 800-294-5979 Fax: 888-836-0730 Exchange Phone: 855-582-2022 Fax: 855-245-2134 Medical Specialty Medications (NLX) All Plans Phone: 844-345-2803 Fax: 844-851-0882 Cinqair, Fasenra, Nucala and Xolair solutions are Medical Benefit only Exceptions Dupixent, Fasenra Pen, Nucala Pen and Xolair Pen are Pharmacy Benefit Only and obtained through specialty pharmacy Overview Cinqair and Fasenra are interleukin-5 antagonist monoclonal antibodies indicated for: • As add-on maintenance treatment of severe asthma for members with an eosinophilic phenotype. Nucala is an interleukin-5 antagonist monoclonal antibody indicated for: • Treatment of severe asthma with an eosinophilic phenotype • Eosinophilic granulomatosis with polyangiitis • Hypereosinophilic syndrome (HES) Dupixent is an interleukin-4 receptor alpha agonist indicated for: • Atopic Dermatitis • Chronis rhinosinusitis with nasal polyps
    [Show full text]
  • Samaritan Fund
    Items supported by the Samaritan Fund (a) Non-drug Items supported by the Fund (b) Other items supported by the Samaritan Fund Mechanism (c) Self-financed Drugs supported by the Samaritan Fund (SF) and Community Care Fund (CCF) Medical Assistance Programme (First Phase Programme) (for specified self- financed cancer drugs) (a) Non-drug Items supported by the Fund 1. Percutaneous Transluminal Coronary Angioplasty (PTCA) and other consumables for interventional cardiology 2. Cardiac Pacemakers 3. Myoelectric Prosthesis 4. Custom-made Prosthesis 5. Appliances for prosthetic and orthotic services, physiotherapy and occupational therapy services (e.g. prosthesis) 6. Home use equipment and appliances (e.g. wheelchair, replacement of external speech processor for patients done with cochlear implant) 7. Gamma knife surgery 8. Harvesting of marrow in a foreign country for marrow transplant The Fund will only support the model which can meet the basic medical needs of the patients. (b) Other items supported by the Samaritan Fund Mechanism 1. Positron Emission Tomography (PET) service (c) Drugs supported by the Samaritan Fund The following specific self-financed drugs are supported by the Samaritan Fund: Item Drug Types of Clinical indications diseases 1 Abatacept Rheumatology Rheumatoid arthritis 2a Adalimumab Dermatology Severe psoriasis 2b Ophthalmology Non-infectious intermediate, posterior and panuveitis 2c Paediatric chronic non-infectious anterior uveitis 2d Rheumatology Ankylosing spondylitis 2e Juvenile idiopathic arthritis 2f Psoriatic
    [Show full text]