Sean D. Sullivan

Global strategy for asthma management and prevention: GINA executive summary

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.

International variation in the prevalence of COPD (The BOLD Study): a population-based prevalence study

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a growing cause of morbidity and mortality worldwide, and accurate estimates of the prevalence of this disease are needed to anticipate the future burden of COPD, target key risk factors, and plan for providing COPD-related health services. We aimed to measure the prevalence of COPD and its risk factors and investigate variation across countries by age, sex, and smoking status. METHODS Participants from 12 sites (n=9425) completed postbronchodilator spirometry testing plus questionnaires about respiratory symptoms, health status, and exposure to COPD risk factors. COPD prevalence estimates based on the Global Initiative for Chronic Obstructive Lung Disease staging criteria were adjusted for the target population. Logistic regression was used to estimate adjusted odds ratios (ORs) for COPD associated with 10-year age increments and 10-pack-year (defined as the number of cigarettes smoked per day divided by 20 and multiplied by the number of years that the participant smoked) increments. Meta-analyses provided pooled estimates for these risk factors. FINDINGS The prevalence of stage II or higher COPD was 10.1% (SE 4.8) overall, 11.8% (7.9) for men, and 8.5% (5.8) for women. The ORs for 10-year age increments were much the same across sites and for women and men. The overall pooled estimate was 1.94 (95% CI 1.80-2.10) per 10-year increment. Site-specific pack-year ORs varied significantly in women (pooled OR=1.28, 95% CI 1.15-1.42, p=0.012), but not in men (1.16, 1.12-1.21, p=0.743). INTERPRETATION This worldwide study showed higher levels and more advanced staging of spirometrically confirmed COPD than have typically been reported. However, although age and smoking are strong contributors to COPD, they do not fully explain variations in disease prevalence-other factors also seem to be important. Although smoking cessation is becoming an increasingly urgent objective for an ageing worldwide population, a better understanding of other factors that contribute to COPD is crucial to assist local public-health officials in developing the best possible primary and secondary prevention policies for their regions.

An Official American Thoracic Society/European Respiratory Society Statement: Asthma Control and Exacerbations Standardizing Endpoints for Clinical Asthma Trials and Clinical Practice

BACKGROUND The assessment of asthma control is pivotal to the evaluation of treatment response in individuals and in clinical trials. Previously, asthma control, severity, and exacerbations were defined and assessed in many different ways. PURPOSE The Task Force was established to provide recommendations about standardization of outcomes relating to asthma control, severity, and exacerbations in clinical trials and clinical practice, for adults and children aged 6 years or older. METHODS A narrative literature review was conducted to evaluate the measurement properties and strengths/weaknesses of outcome measures relevant to asthma control and exacerbations. The review focused on diary variables, physiologic measurements, composite scores, biomarkers, quality of life questionnaires, and indirect measures. RESULTS The Task Force developed new definitions for asthma control, severity, and exacerbations, based on current treatment principles and clinical and research relevance. In view of current knowledge about the multiple domains of asthma and asthma control, no single outcome measure can adequately assess asthma control. Its assessment in clinical trials and in clinical practice should include components relevant to both of the goals of asthma treatment, namely achievement of best possible clinical control and reduction of future risk of adverse outcomes. Recommendations are provided for the assessment of asthma control in clinical trials and clinical practice, both at baseline and in the assessment of treatment response. CONCLUSIONS The Task Force recommendations provide a basis for a multicomponent assessment of asthma by clinicians, researchers, and other relevant groups in the design, conduct, and evaluation of clinical trials, and in clinical practice.

Outcomes for COPD pharmacological trials: from lung function to biomarkers

The American Thoracic Society/European Respiratory Society jointly created a Task Force on “Outcomes for COPD pharmacological trials: from lung function to biomarkers” to inform the chronic obstructive pulmonary disease research community about the possible use and limitations of current outcomes and markers when evaluating the impact of a pharmacological therapy. Based on their review of the published literature, the following document has been prepared with individual sections that address specific outcomes and markers, and a final section that summarises their recommendations.

Global epidemiology of hepatitis B virus.

The burden of hepatitis B virus (HBV) disease and efforts to control infection will determine the future size of the population requiring treatment of HBV infection. To quantify the current prevalence of HBV infection and to reexamine the epidemiology of HBV infection, a structured review was conducted that focused on available primary literature for over 30 countries worldwide. The prevalence of chronic HBV infection continues to be highly variable, ranging over 10% in some Asian and Western Pacific countries to under 0.5% in the United States and northern European countries. The current global estimate of the number of HBV infected individuals is 350 million. Routes of transmission include vertical (mother to child or generation to generation through close contact and sanitary habits), early life horizontal transmission (through bites, lesions, and sanitary habits), and adult horizontal transmission (through sexual contact, intravenous drug use, and medical procedure exposure) and are evident to varying degrees in every country. Younger age at acquisition of infection continues to be the most important predictor of chronic carriage. However, the choice of serologic markers, temporal influences, and representativeness of the study population limit comparability of HBV seroprevalence results. HBV vaccination programs will decrease the future global burden of HBV infection and evidence of reduced burden is mounting in country-specific populations, but vaccination programs have still not been implemented in all countries, thereby maintaining reservoirs of infection and continued HBV transmission. Regardless of vaccination, large numbers of persons are infected with HBVor will become infected. Preventing the most severe HBV disease consequences in infected individuals, such as cirrhosis and hepatocellular carcinoma, will require appropriate therapeutic agents.

A new perspective on concepts of asthma severity and control

Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society Task Force, identifies the need for separate concepts of control and severity, describes their evolution in asthma guidelines and provides a framework for understanding the relationship between current concepts of asthma phenotype, severity and control. “Asthma control” refers to the extent to which the manifestations of asthma have been reduced or removed by treatment. Its assessment should incorporate the dual components of current clinical control (e.g. symptoms, reliever use and lung function) and future risk (e.g. exacerbations and lung function decline). The most clinically useful concept of asthma severity is based on the intensity of treatment required to achieve good asthma control, i.e. severity is assessed during treatment. Severe asthma is defined as the requirement for (not necessarily just prescription or use of) high-intensity treatment. Asthma severity may be influenced by the underlying disease activity and by the patients phenotype, both of which may be further described using pathological and physiological markers. These markers can also act as surrogate measures for future risk.

The efficacy of silver alloy-coated urinary catheters in preventing urinary tract infection: a meta-analysis

PURPOSE Indwelling urinary catheters are implicated in most cases of nosocomial urinary tract infection. Silver-coating of catheters may reduce the risk of these infections; however, trials have provided mixed results. We performed a meta-analysis to estimate the effectiveness of silver-coated urinary catheters. SUBJECTS AND METHODS Published or unpublished articles were sought using MEDLINE, reference review, and correspondence with original authors, catheter manufacturers, and experts. Trials using silver-coated urinary catheters in the treatment group and uncoated urinary catheters in the control group were included. Bacteriuria, as evaluated by urine culture, was the outcome variable used to indicate urinary tract infection. Summary odds ratios (OR) and 95% confidence intervals (CI) were calculated using Mantel-Haenszel methods with a fixed-effects model. RESULTS Of 117 reports retrieved, eight trials with a total of 2,355 patients satisfied inclusion criteria. The summary OR for urinary tract infection was 0.59 (95% CI, 0.42 to 0.84) indicating a significant benefit in the patients receiving silver-coated catheters. A test of heterogeneity, however, indicated that the odds ratios varied significantly among studies. Silver alloy catheters (OR = 0.24; 95% CI, 0.11 to 0.52) were significantly more protective against bacteriuria than silver oxide catheters (OR = 0.79; 95% CI, 0.56 to 1.10). CONCLUSIONS This meta-analysis clarifies discrepant results among trials of silver-coated urinary catheters by revealing that silver alloy catheters are significantly more effective in preventing urinary tract infections than are silver oxide catheters. Though silver alloy urinary catheters cost about

Incidence and long-term cost of steroid-related side effects after renal transplantation.

6 more than standard urinary catheters, they may be worth the extra cost since catheter-related infection is a common cause of nosocomial infection and bacteremia.

The coming epidemic of obesity in elderly Americans

Corticosteroids are an essential component of most immunosuppressive regimens currently used in renal transplantation because of their efficacy in reducing acute rejection and improving graft survival. Steroids, however, are associated with numerous side effects that lead to increased patient morbidity and mortality. The incidence and economic cost of steroid-related side effects have not been quantitatively assessed. Thus, based on a systematic review of the published literature, we estimated the incidence of steroid-related hypertension (15%), posttransplantation diabetes mellitus (10%), peripheral fractures (2% per year), avascular necrosis of the hip (8%), and cataracts (22%). In addition, we estimated that approximately 5% of patients who have cataracts or avascular necrosis of the hip require surgery. We used these literature-based estimates in a model to project the costs of treating side effects over a 10-year posttransplantation time frame for a 50-patient cohort that represented an average-sized renal transplant center. Steroid-induced hypertension and its complications were the most expensive side effect (

Budget impact analysis-principles of good practice: report of the ISPOR 2012 Budget Impact Analysis Good Practice II Task Force.

93,900), followed closely by posttransplantation diabetes (