Shaun Holt

Bio: Shaun Holt is an academic researcher from Wellington Management Company. The author has contributed to research in topics: Asthma & Fluticasone propionate. The author has an hindex of 17, co-authored 49 publications receiving 4544 citations. Previous affiliations of Shaun Holt include Victoria University of Wellington.

The global burden of asthma: executive summary of the GINA Dissemination Committee Report

Abstract: It is estimated that as many as 300 million people of all ages, and all ethnic backgrounds, suffer from asthma and the burden of this disease to governments, health care systems, families, and patients is increasing worldwide. In 1989 the Global Initiative for Asthma (GINA) program was initiated in an effort to raise awareness among public health and government officials, health care workers, and the general public that asthma was on the increase. The GINA program recommends a management program based on the best available scientific evidence to provide effective medical care for asthma tailored to local health care systems and resources. Working in continued collaboration with leaders in asthma care from many countries, GINA sponsors World Asthma Day (first Tuesday in May) which has been extremely successful. A vast number of people have made a commitment to bring awareness about the burden of asthma to their local health care officials, and to implement programs of effective asthma care. Beginning in 2003, the theme of World Asthma Day has been the ‘‘Global Burden of Asthma.’’ GINA commissioned Professor Richard Beasley, Wellington, New Zealand (member, GINA Dissemination Committee) to provide available data on the burden of asthma. A summary of this report is provided in this publication; the full document with data sets for 20 different regions worldwide may be obtained from the GINA website (http://www.ginasthma.com). Professor Beasley and his colleagues obtained data on the burden of asthma from literature primarily published through the International StudyofAsthmaandAllergies in Childhood (ISAAC) and the European Community Respiratory Health Survey (ECHRS). Methodologies differ in these studies, and epidemiological data on asthma are very difficult to collect, as Professor Beasley carefully describes in his segment on ‘‘Methodological Issues.’’ Nonetheless, the full report provides a wealth of information, along with a large number of scientific references. The study regions have been grouped according to geographical, political, historical, and racial considerations based on official data from WHO, the United Nations (UN), and other sources, and to some extent, the availability of asthma epidemiological data within the study region. Using the United Nations World Population Prospect Population Database (http://esa.un.org/unpp) as a source within each region, all countries were included, and in some cases territories and dependencies if specific asthma epidemiological data were available. For simplicity some data from small territories have been omitted or lumped in a larger sub-regional unit. The report will be updated as new information becomes available and following feedback from individual countries and regions. The GINA Executive Committee is indebted to Professor Beasley and his colleagues for providing this report that will be an invaluable source of information for those who wish to explore available data on the burden of asthma by region. It will be extremely useful to develop background materials for World Asthma Day activities in 2004 and well into the future. Matthew Masoli, Denise Fabian, Shaun Holt, Richard Beasley for the Global Initiative for Asthma (GINA) Program

Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis.

Abstract: Objective: To examine the dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma. Design: Meta-analysis of placebo controlled, randomised clinical trials that presented data on at least one outcome measure of asthma and that used at least two different doses of fluticasone. Setting: Medline, Embase, and GlaxoWellcome9s internal clinical study registers. Main outcome measures: FEV 1 , morning and evening peak expiratory flow, night awakenings, β agonist use, and major exacerbations. Results: Eight studies, with 2324 adolescents and adults with asthma, met the inclusion criteria. Data on doses of >500 µg/day were limited. The dose-response curve for the raw data began to reach a plateau at around 100-200 µg/day and peaked by 500 µg/day. A negative exponential model for the data, without meta-analysis, indicated that 80% of the benefit at 1000 µg/day was achieved at doses of 70-170 µg/day and 90% by 100-250 µg/day. A quadratic meta-regression showed that the maximum achievable efficacy was obtained by doses of around 500 µg/day. The odds ratio for patients remaining in a study at a dose of 200 µg/day, compared with higher doses, was 0.73 (95% confidence interval 0.49 to 1.08). Comparison of the standardised difference in FEV 1 for an inhaled dose of 200 µg/day against higher doses showed a difference in FEV 1 of 0.13 of a standard deviation (−0.02 to 0.29). Conclusions: In adolescent and adult patients with asthma, most of the therapeutic benefit of inhaled fluticasone is achieved with a total daily dose of 100-250 µg, and the maximum effect is achieved with a dose of around 500 µg/day. However, these findings were limited by the lack of data on individual patients and by the paucity of dose-response studies that included doses of >500 µg/day. What is already known on this topic Inhaled corticosteroids are recommended for most patients with asthma, with the dose being increased as required to obtain control A therapeutic dose range of fluticasone propionate of 200-2000 µg/day is recommended in the British National Formulary for adults with asthma What this study adds Published data are insufficient to determine with confidence the dose-response relation of inhaled fluticasone at doses of >500 µg/day The dose-response curve for inhaled fluticasone in moderate to severe asthma in adolescents and adults, for all major clinical outcome measures, including exacerbations, begins to plateau at 100-200 µg/day and peaks at around 500 µg/day This study partially explains why adding a long acting β agonist to inhaled corticosteroids is more efficacious than increasing the dose of inhaled steroid beyond this dose range

An audiovisual reminder function improves adherence with inhaled corticosteroid therapy in asthma

Abstract: Background Adherence to medication regimens is poor in the management of chronic diseases, including asthma. Objective To determine whether an audiovisual reminder device improves adherence with inhaled corticosteroid (ICS) therapy in adult asthma. Methods A randomized open-label parallel group study of 110 adult or adolescent subjects with asthma was undertaken. Subjects were randomized to receive 24 weeks of fluticasone propionate 250 μg, 1 actuation twice daily via a metered dose inhaler (MDI) with or without an audiovisual reminder function (AVRF). All MDIs had electronic covert adherence monitors. The primary outcome variable was adherence, defined as the proportion of medication taken as prescribed over the final 12 weeks of the study. Adherence was also assessed as the proportion of subjects who took >50%, >80%, or >90% of prescribed medication. Results The proportion of medication taken in the last 12 weeks was greater in the AVRF group (93%) compared with the control group (74%), with a difference of 18% (95% confidence interval [CI] 10-26%; P 50%, >80%, or >90% of their medication was greater in the AVRF group, with a ratio of proportions adherent of 1.33 (95% CI, 1.10-1.61; P = .003), 2.27 (95% CI, 1.56-3.3; P P Conclusion An audiovisual reminder function can significantly improve adherence with ICS therapy in adult asthma. Clinical implications An audiovisual reminder function has potential to improve adherence with medication regimens across a wide spectrum of diseases, in both research and clinical practice.

Moderate dose inhaled corticosteroids plus salmeterol versus higher doses of inhaled corticosteroids in symptomatic asthma

Abstract: Background: There is uncertainty as to the dose of inhaled corticosteroids (ICS) at which to start concomitant long acting β agonist (LABA) treatment in patients with asthma not adequately controlled by ICS alone. Methods: A meta-analysis was carried out of randomised, double blind clinical trials that compared the efficacy of adding salmeterol to moderate doses of ICS (fluticasone propionate 200 μg/day or equivalent) with increasing the ICS dose by at least twofold in symptomatic adult patients with asthma. The main outcome measures were the number of subjects withdrawn from the study due to asthma and the number of subjects with at least one moderate or severe exacerbation. Results: Twelve studies with a total of 4576 subjects met the inclusion criteria for the analyses. The number of subjects withdrawn due to asthma and with at least one moderate or severe exacerbation was higher in the high dose ICS group (odds ratios 1.58, 95% CI 1.12 to 2.24 and 1.35, 95% CI 1.10 to 1.66, respectively). For the secondary outcome variables (forced expiratory volume in 1 second, morning and evening peak expiratory flow, and daytime β agonist use) there was significantly greater benefit in the salmeterol group. Conclusions: This meta-analysis shows that the addition of salmeterol to moderate doses of ICS (fluticasone 200 μg/day or equivalent) in patients with asthma symptomatic at that dose results in significantly greater clinical benefit than increasing the dose of ICS by twofold or more.

Harrison's Principles of Internal Medicine

Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen)

Abstract: Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations. In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease. This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work. The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available. Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed. The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.

A systematic review of the literature

Abstract: OBJECTIVE — To systematically review the incidence of posttransplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management. RESEARCH DESIGN AND METHODS — We searched databases (MEDLINE, EMBASE, the Cochrane Library, and others) from inception to September 2000, reviewed bibliographies in reports retrieved, contacted transplantation experts, and reviewed specialty journals. Two reviewers independently determined report inclusion (original studies, in all languages, of PTD in adults with no history of diabetes before transplantation), assessed study methods, and extracted data using a standardized form. Meta-regression was used to explain between-study differences in incidence. RESULTS — Nineteen studies with 3,611 patients were included. The 12-month cumulative incidence of PTD is lower (10% in most studies) than it was 3 decades ago. The type of immunosuppression explained 74% of the variability in incidence (P 0.0004). Risk factors were patient age, nonwhite ethnicity, glucocorticoid treatment for rejection, and immunosuppression with high-dose cyclosporine and tacrolimus. PTD was associated with decreased graft and patient survival in earlier studies; later studies showed improved outcomes. Randomized trials of treatment regimens have not been conducted. CONCLUSIONS — Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients. Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients, paying particular attention to interactions with immunosuppressive drugs. Diabetes Care 25:583–592, 2002

Global strategy for asthma management and prevention: GINA executive summary.

Abstract: Asthma is a serious health problem throughout the world During the past two decades, many scientific advances have improved our understanding of asthma and ability to manage and control it effectively However, recommendations for asthma care need to be adapted to local conditions, resources and services Since it was formed in 1993, the Global Initiative for Asthma, a network of individuals, organisations and public health officials, has played a leading role in disseminating information about the care of patients with asthma based on a process of continuous review of published scientific investigations A comprehensive workshop report entitled "A Global Strategy for Asthma Management and Prevention", first published in 1995, has been widely adopted, translated and reproduced, and forms the basis for many national guidelines The 2006 report contains important new themes First, it asserts that "it is reasonable to expect that in most patients with asthma, control of the disease can and should be achieved and maintained," and recommends a change in approach to asthma management, with asthma control, rather than asthma severity, being the focus of treatment decisions The importance of the patient-care giver partnership and guided self-management, along with setting goals for treatment, are also emphasised

Interventions for enhancing medication adherence.

Abstract: Background People who are prescribed self-administered medications typically take less than half the prescribed doses. Efforts to assist patients with adherence to medications might improve the benefits of prescribed medications, but also might increase their adverse effects. Objectives To update a review summarizing the results of randomized controlled trials (RCTs) of interventions to help patients follow prescriptions for medications for medical problems, including mental disorders but not addictions. Search methods We updated searches of The Cochrane Library, MEDLINE, CINAHL, EMBASE, International Pharmaceutical Abstracts (IPA), PsycINFO (all via OVID) and Sociological Abstracts (via CSA) in January 2007 with no language restriction. We also reviewed bibliographies in articles on patient adherence and articles in our personal collections, and contacted authors of relevant original and review articles. Selection criteria Articles were selected if they reported an unconfounded RCT of an intervention to improve adherence with prescribed medications, measuring both medication adherence and treatment outcome, with at least 80% follow-up of each group studied and, for long-term treatments, at least six months follow-up for studies with positive initial findings. Data collection and analysis Study design features, interventions and controls, and results were extracted by one review author and confirmed by at least one other review author. We extracted adherence rates and their measures of variance for all methods of measuring adherence in each study, and all outcome rates and their measures of variance for each study group, as well as levels of statistical significance for differences between study groups, consulting authors and verifying or correcting analyses as needed. The studies differed widely according to medical condition, patient population, intervention, measures of adherence, and clinical outcomes. Therefore, we did not feel that quantitative analysis was scientifically justified; rather, we conducted a qualitative analysis. Main results For short-term treatments, four of ten interventions reported in nine RCTs showed an effect on both adherence and at least one clinical outcome, while one intervention reported in one RCT significantly improved patient adherence, but did not enhance the clinical outcome. For long-term treatments, 36 of 83 interventions reported in 70 RCTs were associated with improvements in adherence, but only 25 interventions led to improvement in at least one treatment outcome. Almost all of the interventions that were effective for long-term care were complex, including combinations of more convenient care, information, reminders, self-monitoring, reinforcement, counseling, family therapy, psychological therapy, crisis intervention, manual telephone follow-up, and supportive care. Even the most effective interventions did not lead to large improvements in adherence and treatment outcomes. Authors' conclusions For short-term treatments several quite simple interventions increased adherence and improved patient outcomes, but the effects were inconsistent from study to study with less than half of studies showing benefits. Current methods of improving adherence for chronic health problems are mostly complex and not very effective, so that the full benefits of treatment cannot be realized. High priority should be given to fundamental and applied research concerning innovations to assist patients to follow medication prescriptions for long-term medical disorders.