DOCSLIB.ORG

Delaying and Reversing Frailty: a Systematic Review of Primary Care Interventions

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Delaying and Reversing Frailty: a Systematic Review of Primary Care Interventions Research John Travers, Roman Romero-Ortuno, Jade Bailey and Marie-Therese Cooney Delaying and reversing frailty: a systematic review of primary care interventions INTRODUCTION Abstract Frailty has been described as the most Frailty has long been in the lexicon of problematic expression of population ageing Background everyday language. ‘How easily the wind in the context of this considerable growth.3 It Recommendations for routine frailty screening overturns a frail tree’, Buddha reflected has forced fundamental changes in national in general practice are increasing as frailty 1 prevalence grows. In England, frailty identification some 2500 years ago. From such historic health policies. For example, since 2017 became a contractual requirement in 2017. prevalence has come an inherited instinct the new General Medical Services (GMS) However, there is little guidance on the most for recognising frailty. However, it is only contract in England mandates that all effective and practical interventions once frailty primary care practices use an appropriate has been identified. in recent years that frailty has come into focus for more rigorous medical definition tool to identify patients aged ≥65 years who Aim in a shift of emphasis from single-system are living with moderate or severe frailty. To assess the comparative effectiveness and ease of implementation of frailty interventions in conditions to unifying constructs for holistic For patients living with severe frailty, the primary care. patient care. practice must undertake a clinical review, Frailty can be described as a state of provide an annual medication review, Design and setting A systematic review of frailty interventions in physiological vulnerability with diminished discuss whether the patient has fallen in primary care. capacity to manage external stressors.2,3 the last 12 months, activate an enriched Summary Care Record at the patient’s Method It increases the risks of illness, falls, 2,3 Scientific databases were searched from dependency, disability, and death. request (if not already in place), and provide inception to May 2017 for randomised controlled Frailty is becoming a more common any other clinically relevant interventions.7 trials or cohort studies with control groups on challenge as populations age and life A variety of tools has been proposed primary care frailty interventions. Screening 8,9 methods, interventions, and outcomes were expectancy lengthens. The prevalence of for frailty screening in primary care. A analysed in included studies. Effectiveness was frailty is estimated at 10.7% in adults aged commonly used method is Fried’s frailty scored in terms of change of frailty status or ≥65 years and increases to some 50% in phenotype10 (three or more criteria from: frailty indicators and ease of implementation in those 80 years of age.4 The United Nations exhaustion, unexplained weight loss, terms of human resources, marginal costs, and > time requirements. estimates that the world population of slowness, weakness, and low physical individuals aged >60 years will more than activity, with one or two criteria present Results double from 962 million in 2017 to 2.1 billion defining pre-frailty). The cumulative deficit A total of 925 studies satisfied search criteria and 11 46 were included. There were 15690 participants in 2050, whereas the population of individuals model proposed by Rockwood and Mitnitski (median study size was 160 participants). Studies aged >80 years will triple from 137 million to provides a frailty index based on the presence reflected a broad heterogeneity. There were 17 425 million in the same period.5 In the UK, of deficits as a proportion of total measured. different frailty screening methods. Of the frailty interventions, 23 involved physical activity and the number of individuals aged >65 years There are several other indices, checklists, other interventions involved health education, is estimated to grow from 10.4 million to and indicators.12–14 A general model of frailty nutrition supplementation, home visits, hormone 12.4 million by 2025 and life expectancy at that captures commonly involved domains is supplementation, and counselling. A significant 65 years is set to increase by 1.7 years.6 shown in Figure 1. improvement of frailty status was demonstrated in 71% (n = 10) of studies and of frailty indicators in 69% (n=22) of studies where measured. Interventions with both muscle strength training J Travers, MB BCh BAO, BE, MBA, senior house Address for correspondence and protein supplementation were consistently officer, Department of Geriatric Medicine, St John Travers, Department of Geriatric Medicine, placed highest for effectiveness and ease of Vincent’s University Hospital and Trinity College St Vincent’s University Hospital, Dublin 4, Ireland. implementation. Dublin HSE Specialist Training Programme in General Practice, Dublin. R Romero- Ortuno, Email: [email protected] Conclusion Lic Med, MSc, PhD, MRCP(UK), associate Submitted: 30 May 2018; Editor’s response: A combination of muscle strength training and professor, consultant physician, Global Brain final acceptance: protein supplementation was the most effective Health Institute (GBHI), Trinity College Dublin, 29 June 2018; 18 July 2018. intervention to delay or reverse frailty and the Mercer’s Institute for Successful Aging, St James’s ©British Journal of General Practice easiest to implement in primary care. A map of Hospital, Dublin. J Bailey, research assistant, This is the full-length article (published online interventions was created that can be used to School of Medicine, University College Dublin, 4 Dec 2018) of an abridged version published in inform choices for managing frailty. Dublin. MT Cooney, PhD, MRCPI, consultant physician, Department of Geriatric Medicine, St print. Cite this version as: Br J Gen Pract 2018; Keywords Vincent’s University Hospital, Dublin. DOI: https://doi.org/10.3399/bjgp18X700241 feasibility; frailty; primary care; systematic review. e61 British Journal of General Practice, January 2019 interventions. The aim of the present study How this fits in was to map their comparative effectiveness Frailty screening is increasingly and ease of implementation, and help recommended in primary care and in some inform practitioners and patients on the cases contractually required, but there most appropriate choices. is a lack of guidance on interventions, once frailty has been identified. This study METHOD outlines both the relative effectiveness A search of PubMed, CINAHL, the Cochrane and ease of implementation of frailty Library Register of Controlled Trials, and interventions in primary care, and these PEDro for English language articles using findings may help the choice of appropriate primary care interventions. the terms ‘primary care’ or ‘community’; ‘screening’ or ‘intervention’ or ‘integrated- care’; and ‘frailty’ or ‘pre-frail’ was conducted. The search was conducted from A common element in frailty tools is inception to May 2017 by one researcher. A a consideration of biological age rather second researcher repeated the search in than chronological age alone. This fits the May 2018 to confirm the results and add biopsychosocial model of primary care, and any further findings. Any clarifications were its use may help identify those who are resolved by two other researchers. at higher risk of adverse outcomes and Studies were selected following an promote equity of access to services.9 The assessment of titles and abstracts. Studies ability of the frailty model to capture risk chosen for inclusion were randomised and biological age in this way has pushed controlled trials (RCTs) or cohort studies the boundaries of care for a population’s with control groups, which assessed most vulnerable patients. This advance interventions aimed at preventing or and the increase in prevalence have treating frailty in a primary care setting, driven international consensus guidance and that quantified outcomes such as to recommend identification of frailty in the measurement of a physical frailty routine clinical encounters.15,16 phenotype, a frailty index, or a similar Identification of frailty was made a established measurement. There was contractual requirement for GPs in England no restriction on age of participants in from April 2017. However, there appears the search criteria. Studies that involved to be a lack of clear guidance on the most secondary or tertiary interventions were effective and practical interventions for excluded; letters, case studies, abstract- frailty once identified. There also appears only publications, and editorials were also to be no consistent approach to how excluded. frailty is dealt with in general practice at The researchers recorded the type of present. It seemed, therefore, both timely study (for example, RCT or cohort), frailty and necessary to conduct a systematic Figure 1. Domains commonly included in frailty screening method (for example, Fried), definitions. review of the evidence on primary care study size, length of study, intervention, outcome measure, and outcome for each study included. Capacity An analytical tool for comparing a set of heterogeneous interventions that was too diverse for meta-analysis was devised by the authors and a scoring system to map Robustness relative effectiveness and relative ease of Energy Power (the capacity to withstand (the capacity to do work: (the rate of doing work: implementation (summarised in Figure 2) stressors: favourable bone grip strength) walking
Load more

Recommended publications
  • The Effects of Targeted Deletion of the Aromatase Enzyme on Prostatic Contractile Responses to Noradrenaline in Mice
    495 The effects of targeted deletion of the aromatase enzyme on prostatic contractile responses to noradrenaline in mice Katherine T Gray, Jennifer L Short, Evan R Simpson1 and Sabatino Ventura Prostate Research Co-operative, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia 1Prince Henry’s Institute of Medical Research, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia (Correspondence should be addressed to S Ventura; Email: [email protected]) Abstract This investigation aimed to see whether a change in the concentration-dependent contractions. Prazosin (0.3 mM) oestrogen to androgen ratio alters prostate contractility. Isolated attenuated the responses induced by noradrenaline and EFS in organ bath studies using prostates from aromatase knockout all mice (P%0.019, nZ5–7), while cocaine (10 mM) attenuated (ArKO) mice which were homozygous (ArKOK/K)and the responses evoked by tyramine (P!0.001, nZ6). There were heterozygous (ArKOC/K) for the disrupted aromatase cyp19 no genotype differences in EFS- and noradrenaline-induced gene and wild-type littermates (ArKOC/C) were conducted. responses (PR0.506, nZ10–13). Prostates from ArKOK/K The distribution of noradrenergic nerves was visualized using and ArKOC/K mice were more sensitive to tyramine than the sucrose–potassium phosphate–glyoxylic acid method. prostates from ArKOC/C mice (P!0.001, nZ11–13). Dense ArKOK/K mice had increased prostate weights compared adrenergic innervation of the prostate was similar in all mice. with ArKOC/C mice. Frequency–response curves to electrical These results suggest that although the absence of aromatase field stimulation (EFS; 0.5 ms pulse duration, 60 V,0.1–20 Hz) increases prostatic growth, this translates only to a subtle and yielded frequency-dependent contractions, while noradrenaline selective increase in contractility in mature mice.
    [Show full text]
  • INTERRELATIONSHIPS of the ESTROGEN-PRODUCING ENZYMES NETWORK in BREAST CANCER DISSERTATION Presented in Partial Fulfillment Of
    INTERRELATIONSHIPS OF THE ESTROGEN-PRODUCING ENZYMES NETWORK IN BREAST CANCER DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Wendy L. Rich, M.S. ∗∗∗∗∗ The Ohio State University 2009 Dissertation Committee: Approved by Pui-Kai Li, Ph.D., Adviser Robert W. Brueggemeier, Ph.D. Karl A. Werbovetz, Ph.D. Adviser Graduate Program in Pharmacy Charles L. Shapiro M.D. ABSTRACT In the United States, breast cancer is the most common non-skin malignancy and the second leading cause of cancer-related death in women. However, earlier detection and new, more effective treatments may be responsible for the decrease in overall death rates. Approximately 60% of breast tumors are estrogen receptor (ER) positive and thus their cellular growth is hormone-dependent. Elevated levels of estrogens, even in post- menopausal women, have been implicated in the development and progression of hormone-dependent breast cancer. Hormone therapies seek to inhibit local estrogen action and biosynthesis, which can be produced by pathways utilizing the enzymes aromatase or steroid sulfatase (STS). Cyclooxygenase-2 (COX-2), typically involved in inflammation processes, is a major regulator of aromatase expression in breast cancer cells. STS, COX-2, and aromatase are critical for estrogen biosynthesis and have been shown to be over-expressed in breast cancer. While there continues to be extensive study and successful design of potent aromatase inhibitors, much remains unclear about the regulation of STS and the clinical applications for its selective inhibition. Further studies exploring the relationships of STS with COX-2 and aromatase enzymes will aid in the understanding of its role in cancer cell growth and in the development of future hormone- dependent breast cancer therapies.
    [Show full text]
  • Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DIX to the HTSUS—Continued
    20558 Federal Register / Vol. 60, No. 80 / Wednesday, April 26, 1995 / Notices DEPARMENT OF THE TREASURY Services, U.S. Customs Service, 1301 TABLE 1.ÐPHARMACEUTICAL APPEN- Constitution Avenue NW, Washington, DIX TO THE HTSUSÐContinued Customs Service D.C. 20229 at (202) 927±1060. CAS No. Pharmaceutical [T.D. 95±33] Dated: April 14, 1995. 52±78±8 ..................... NORETHANDROLONE. A. W. Tennant, 52±86±8 ..................... HALOPERIDOL. Pharmaceutical Tables 1 and 3 of the Director, Office of Laboratories and Scientific 52±88±0 ..................... ATROPINE METHONITRATE. HTSUS 52±90±4 ..................... CYSTEINE. Services. 53±03±2 ..................... PREDNISONE. 53±06±5 ..................... CORTISONE. AGENCY: Customs Service, Department TABLE 1.ÐPHARMACEUTICAL 53±10±1 ..................... HYDROXYDIONE SODIUM SUCCI- of the Treasury. NATE. APPENDIX TO THE HTSUS 53±16±7 ..................... ESTRONE. ACTION: Listing of the products found in 53±18±9 ..................... BIETASERPINE. Table 1 and Table 3 of the CAS No. Pharmaceutical 53±19±0 ..................... MITOTANE. 53±31±6 ..................... MEDIBAZINE. Pharmaceutical Appendix to the N/A ............................. ACTAGARDIN. 53±33±8 ..................... PARAMETHASONE. Harmonized Tariff Schedule of the N/A ............................. ARDACIN. 53±34±9 ..................... FLUPREDNISOLONE. N/A ............................. BICIROMAB. 53±39±4 ..................... OXANDROLONE. United States of America in Chemical N/A ............................. CELUCLORAL. 53±43±0
    [Show full text]
  • A New Aromatase Inhibitor, in Postmenopausal Women
    (CANCERRESEARCH52, 5933-5939, November1, 1992J Phase I and Endocrine Study of Exemestane (FCE 24304), a New Aromatase Inhibitor, in Postmenopausal Women T. R. Jeffry Evans,' Enrico Di Salle, Giorgio Ornati, Mercedes Lassus, Margherita Strolin Benedetti, Eio Pianezzola, and R. Charles Coombes Department ofMedical OncoIoij@,St. Geoa@ge'sHospital Medical School, Creamer Terrace, London SWI7 ORE, England fT. R. I. E.J; Departments of Oncology IE. D. S., G. 0., M. Li and Pharmacokinetics and Metabolism [M. S. B., E. P.J, Farmitalia Carlo Erba, Via Carlo Imbonati, Milan, Italy; and Department of Medical Oncology, Charing Cross Hospital, FuThoin Palace Roa@ London W6 8RF, England (R. C. C.] ABSTRACT aminoglutethimide and fadrozole (CGS 16949A) (7). Objective tumor regression occurred in approximately 21% of patients Aromatase inhibitors are a useful therapeutic option in the manage treated with 4}IAI@@,2witha low incidence of adverse effects; ment of endocrine-dependent advanced breast cancer. A single-dose 4.5% of patients were withdrawn from treatment because of administration of exemestane (FCE 24304; 6-methylenandrosta-l,4-dl ene-3,17-dione), a new Irreversible aromatase inhibitor, was investi side effects. However, 4HAD undergoes extensive metabolism gated in 29 healthy postmenopausal female volunteers. The compound, in the liver to form the inactive glucuronide (8) and conse given at p.o. doses ofO.5, 5, 12.5, 25, 50, 200, 400, and 800 mg(n = 3—4), quently it is recommended that it is given i.m. rather than p.o. was found to be a well tolerated, potent, long-lasting, and specific in The use of aminoglutethimide as an aromatase inhibitor is re hibitor of estrogen biosynthesis.
    [Show full text]
  • Aromatase Inhibitors As Potential Cancer Chemopreventives
    V Vol. 7, 65-78, Januar’, 1998 Cancer Epidemiology, Biomarkers & Prevention 65 Review Aromatase Inhibitors as Potential Cancer Chemopreventives Gary J. Kelloff,t Ronald A. Lubet, Ronald Lieberman, local estrogen production may be an alternative strategy, Karen Eisenhauer, Vernon E. Steele, James A. Crowell, as suggested by the discovery of a unique transcriptional Ernest T. Hawk, Charles W. Boone, and promoter of aromatase gene expression, 1.4, in breast Caroline C. Sigman adipose tissue. The development of drugs that target this Chemoprevention Branch, Division of Cancer Prevention and Control, promoter region may be possible. National Cancer Institute, Bethesda, Maryland 20852 1G. J. K., R. A. L., R. L.. V. E. S., J. A. C., E. T. H., C. W. B.l; and CCS Associates, Mountain View, Califomia 94043 1K. E., C. C. S.] Strategies in Development of Cancer Chemopreventive Agents This paper is the third in a series on strategies used by the Abstract Chemoprevention Branch of the National Cancer Institute to Epidemiological and experimental evidence strongly develop cancer chemoprevention drugs ( 1-3). One chemopre- supports a role for estrogens in the development and ventive strategy for hormone-dependent cancers is to interfere growth of breast tumors. A role for estrogen in prostate with the hormones that stimulate cellular proliferation in these neoplasia has also been postulated. Therefore, one tumors. Among the most important of these targets for inter- chemopreventive strategy for breast and prostate cancers vention are estrogen-responsive tumors. Estrogen production is to decrease estrogen production. This can be can be decreased by inhibiting aromatase, the enzyme cata- accomplished by inhibiting aromatase, the enzyme that lyzing the final, rate-limiting step in estrogen biosynthesis.
    [Show full text]
  • Aromatase Inhibitors Produce Hypersensitivity In
    AROMATASE INHIBITORS PRODUCE HYPERSENSITIVITY IN EXPERIMENTAL MODELS OF PAIN: STUDIES IN VIVO AND IN ISOLATED SENSORY NEURONS Jason Dennis Robarge Submitted to the faculty of the University Graduate School in partial fulfillment of the requirements for the degree Doctor of Philosophy in the Department of Pharmacology and Toxicology, Indiana University September 2014 Accepted by the Graduate Faculty, of Indiana University, in partial fulfillment of the requirements for the degree of Doctor of Philosophy. ___________________________________ David A. Flockhart, M.D., Ph.D., Chair ___________________________________ Jill C. Fehrenbacher, Ph.D. Doctoral Committee ___________________________________ Rajesh Khanna, Ph.D. ___________________________________ Todd C. Skaar, Ph.D. June 9, 2014 ___________________________________ Michael R. Vasko, Ph.D. ii DEDICATION For Dad iii ACKNOWLEDGEMENTS This scientific endeavor was possible with the support, guidance, and collaboration of many individuals at Indiana University. Foremost, I am grateful for the mentorship of two excellent scientists, Dr. David Flockhart and Dr. Michael Vasko, who encouraged me to pursue scientific questions with thoughtful ambition. For the rest of my scientific career, I will always ask two critical questions: “What’s the clinical impact?” and “What’s the question?”. I am also equally thankful for the friendship and mentorship of many members of the Vasko lab family. I enjoyed so many enlightening conversations about scientific and non-scientific matters alike with Dr. Djane Duarte, Dr. Ramy Habashy, Behzad Shariati, and others. I thank Dr. Todd Skaar, Dr. Rajesh Khanna, and Dr. Jill Fehrenbacher for their encouragement and fair critique as members of my committee. I would especially like to thank my family. To my parents, who provided me with every opportunity to pursue higher education and were unwavering in their support and confidence in me.
    [Show full text]
  • Dehydroepiandrosterone: a Potential Therapeutic Agent in the Treatment
    Bentley et al. Burns & Trauma (2019) 7:26 https://doi.org/10.1186/s41038-019-0158-z REVIEW Open Access Dehydroepiandrosterone: a potential therapeutic agent in the treatment and rehabilitation of the traumatically injured patient Conor Bentley1,2,3* , Jon Hazeldine1,3, Carolyn Greig2,4, Janet Lord1,3,4 and Mark Foster1,5 Abstract Severe injuries are the major cause of death in those aged under 40, mainly due to road traffic collisions. Endocrine, metabolic and immune pathways respond to limit the tissue damage sustained and initiate wound healing, repair and regeneration mechanisms. However, depending on age and sex, the response to injury and patient prognosis differ significantly. Glucocorticoids are catabolic and immunosuppressive and are produced as part of the stress response to injury leading to an intra-adrenal shift in steroid biosynthesis at the expense of the anabolic and immune enhancing steroid hormone dehydroepiandrosterone (DHEA) and its sulphated metabolite dehydroepiandrosterone sulphate (DHEAS). The balance of these steroids after injury appears to influence outcomes in injured humans, with high cortisol: DHEAS ratio associated with increased morbidity and mortality. Animal models of trauma, sepsis, wound healing, neuroprotection and burns have all shown a reduction in pro- inflammatory cytokines, improved survival and increased resistance to pathological challenges with DHEA supplementation. Human supplementation studies, which have focused on post-menopausal females, older adults, or adrenal insufficiency have shown that restoring the cortisol: DHEAS ratio improves wound healing, mood, bone remodelling and psychological well-being. Currently, there are no DHEA or DHEAS supplementation studies in trauma patients, but we review here the evidence for this potential therapeutic agent in the treatment and rehabilitation of the severely injured patient.
    [Show full text]
  • Inhibition of Cytochrome P450 Enzymes
    7 Inhibition of Cytochrome P450 Enzymes Maria Almira Correia and Paul R. Ortiz de Monteflano 1. Introduction of P450 inhibitors are available in various reviews"^^^. This chapter focuses on the mecha­ Three steps in the catalytic cycle of nisms of inactivation; thus, most of the chapter is cytochrome P450 (P450, CYP; see Chapters 5 and devoted to the discussion of agents that require 6) are particularly vulnerable to inhibition: (a) the P450 catalysis to fiilfill their inhibitory potential. binding of substrates, (b) the binding of molecular The mechanisms of reversible competitive and oxygen subsequent to the first electron transfer, noncompetitive inhibitors, despite their practical and (c) the catalytic step in which the substrate is importance, are relatively straightforward and are actually oxidized. Only inhibitors that act at one of discussed more briefly. these three steps will be considered in this chapter. Inhibitors that act at other steps in the catalytic cycle, such as agents that interfere with the 2. Reversible Inhibitors electron supply to the hemoprotein by accepting electrons directly from P450 reductase^"^, are not Reversible inhibitors compete with substrates discussed here. for occupancy of the active site and include agents P450 inhibitors can be divided into three that (a) bind to hydrophobic regions of the active mechanistically distinct classes: Agents that site, (b) coordinate to the heme iron atom, or (a) bind reversibly, (b) form quasi-irreversible (c) enter into specific hydrogen bonding or ionic complexes with the heme iron atom, and (c) bind interactions with active-site residues"*"^^. The first irreversibly to the protein or the heme moiety, or mechanism, in which the inhibitor simply competes accelerate the degradation and/or oxidative frag­ for binding to lipophilic domains of the active site, mentation of the prosthetic heme.
    [Show full text]
  • Pros and Cons Controversy on Molecular Imaging and Dynamic
    Open Access Archives of Biotechnology and Biomedicine Research Article Pros and Cons Controversy on Molecular Imaging and Dynamics of Double- ISSN Standard DNA/RNA of Human Preserving 2639-6777 Stem Cells-Binding Nano Molecules with Androgens/Anabolic Steroids (AAS) or Testosterone Derivatives through Tracking of Helium-4 Nucleus (Alpha Particle) Using Synchrotron Radiation Alireza Heidari* Faculty of Chemistry, California South University, 14731 Comet St. Irvine, CA 92604, USA *Address for Correspondence: Dr. Alireza Abstract Heidari, Faculty of Chemistry, California South University, 14731 Comet St. Irvine, CA 92604, In the current study, we have investigated pros and cons controversy on molecular imaging and dynamics USA, Email: of double-standard DNA/RNA of human preserving stem cells-binding Nano molecules with Androgens/ [email protected]; Anabolic Steroids (AAS) or Testosterone derivatives through tracking of Helium-4 nucleus (Alpha particle) using [email protected] synchrotron radiation. In this regard, the enzymatic oxidation of double-standard DNA/RNA of human preserving Submitted: 31 October 2017 stem cells-binding Nano molecules by haem peroxidases (or heme peroxidases) such as Horseradish Peroxidase Approved: 13 November 2017 (HPR), Chloroperoxidase (CPO), Lactoperoxidase (LPO) and Lignin Peroxidase (LiP) is an important process from Published: 15 November 2017 both the synthetic and mechanistic point of view. Copyright: 2017 Heidari A. This is an open access article distributed under the Creative
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • Medicines Regulations 1984 (SR 1984/143)
    Reprint as at 25 October 2018 Medicines Regulations 1984 (SR 1984/143) David Beattie, Governor-General Order in Council At the Government House at Wellington this 5th day of June 1984 Present: His Excellency the Governor-General in Council Pursuant to section 105 of the Medicines Act 1981, and, in the case of Part 3 of the regulations, to section 62 of that Act, His Excellency the Governor-General, acting on the advice of the Minister of Health tendered after consultation with the organisations and bodies that appeared to the Minister to be representatives of persons likely to be substantially affected, and by and with the advice and consent of the Executive Coun- cil, hereby makes the following regulations. Contents Page 1 Title and commencement 5 2 Interpretation 5 Part 1 Classification of medicines 3 Classification of medicines 9 Note Changes authorised by subpart 2 of Part 2 of the Legislation Act 2012 have been made in this official reprint. Note 4 at the end of this reprint provides a list of the amendments incorporated. These regulations are administered by the Ministry of Health. 1 Reprinted as at Medicines Regulations 1984 25 October 2018 Part 2 Standards 4 Standards for medicines, related products, medical devices, 10 cosmetics, and surgical dressings 5 Pharmacist may dilute medicine in particular case 10 6 Colouring substances [Revoked] 10 Part 3 Advertisements 7 Advertisements not to claim official approval 11 8 Advertisements for medicines 11 9 Advertisements for related products 13 10 Advertisements for medical devices 13
    [Show full text]
  • Aromatase Inhibitors for Treatment of Advanced Breast Cancer in Postmenopausal Women (Review)
    Cochrane Database of Systematic Reviews Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women (Review) Gibson L, Lawrence D, Dawson C, Bliss J Gibson L, Lawrence D, Dawson C, Bliss J. Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD003370. DOI: 10.1002/14651858.CD003370.pub3. www.cochranelibrary.com Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women (Review) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 BACKGROUND .................................... 2 OBJECTIVES ..................................... 3 METHODS ...................................... 3 RESULTS....................................... 6 DISCUSSION ..................................... 12 AUTHORS’CONCLUSIONS . 13 ACKNOWLEDGEMENTS . 13 REFERENCES ..................................... 14 CHARACTERISTICSOFSTUDIES . 19 DATAANDANALYSES. 51 Analysis 1.1. Comparison 1 AI versus non-AI, Outcome 1 Overall survival (reported or calculated). 58 Analysis 1.2. Comparison 1 AI versus non-AI, Outcome 2 Progression-free survival (reported or calculated). 59 Analysis 1.3. Comparison 1 AI versus non-AI, Outcome 3 Clinical benefit (assessable). 61 Analysis 1.4. Comparison 1 AI versus non-AI, Outcome 4 Objective response (assessable). 63 Analysis 1.5. Comparison 1 AI versus non-AI, Outcome 5 Clinical benefit (randomised). 65 Analysis 1.6. Comparison 1 AI versus non-AI, Outcome 6 Objective response (randomised). 68 Analysis 2.1. Comparison 2 AI versus non-AI: Toxicity, Outcome 1hotflushes. 70 Analysis 2.2. Comparison 2 AI versus non-AI: Toxicity, Outcome 2nausea.. 72 Analysis 2.3. Comparison 2 AI versus non-AI: Toxicity, Outcome 3 vomiting. 73 Analysis 2.4. Comparison 2 AI versus non-AI: Toxicity, Outcome 4diarrhoea.
    [Show full text]