Intraclass Difference in Pneumonia Risk with Fluticasone and Budesonide in COPD: A Systematic Review of Evidence from Direct-Comparison Studies.

Background: Inhaled corticosteroids (ICS) are widely used and recommended to treat chronic obstructive pulmonary disease (COPD). While generally considered safe, several studies demonstrated an increased risk of pneumonia with the use of ICS in COPD patients. Although all ICS indicated for COPD carry the class labeling warning of increased pneumonia risk, evidence suggests an intraclass difference in the risk of pneumonia between inhaled budesonide and fluticasone. To date, systematic reviews of direct-comparison studies have not been performed to assess if an intraclass difference exists. Research Question: This review investigated whether there is an intraclass difference in risk of pneumonia between inhaled fluticasone and budesonide, the 2 most commonly used ICS in COPD. Study Design and Methods: A search of the medical literature was conducted in PubMed and Embase for the time period of 01/01/69-05/31/19. The search strategy combined terms that defined the patient/disease type, exposures, outcome, and the study/publication type. Descriptive and comparative statistics reported for fluticasone- and budesonide-containing products in each study, including data for pneumonia event subgroups, were extracted and reported by dose, seriousness, or practice setting. Controlled clinical trials and observational studies meeting the inclusion criteria were assessed for methodologic quality by using the appropriate tool from the list of study quality assessment tools developed by the National Institutes of Health. Results: The summary relative risk (RR) ratio across 5 included studies (57,199 patients) was 1.13 (95% CI: 1.09-1.19), representing a 13.5% increased risk of pneumonia among fluticasone users compared to budesonide users. Similarly, summary RR ratio for serious pneumonia implied a 14.4% increased risk of serious pneumonia among fluticasone users compared to budesonide users (pooled RR: 1.14; 95% CI: 1.09-1.20). Interpretation: There is likely a clinically important intraclass difference in the risk of pneumonia between fluticasone- and budesonide-containing inhaled medications in COPD.

Benefits of glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) in improving lung function and reducing exacerbations in patients with moderate-to-very severe COPD: a pooled analysis of the PINNACLE studies.

BACKGROUND: The Phase III PINNACLE studies assessed the efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI), a dual long-acting bronchodilator for chronic obstructive pulmonary disease (COPD). Here we present a pre-specified pooled analysis of PINNACLE-1, PINNACLE-2, and PINNACLE-4. METHODS: PINNACLE-1, -2, and -4 were multicenter, double-blind, randomized controlled trials that enrolled patients with moderate-to-very severe COPD, with no requirement for exacerbation history or a high symptom burden. Patients received GFF MDI 18/9.6 µg, glycopyrrolate (GP) MDI 18 µg, formoterol fumarate (FF) MDI 9.6 µg, or placebo MDI, twice-daily for 24 weeks. The primary endpoint of the pooled analysis was the change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) at week 24. Secondary endpoints included COPD exacerbations and clinically important deterioration (CID). Adverse events were also assessed. RESULTS: The pooled intent-to-treat population included 4983 patients; of these, 61.9% had a COPD assessment test (CAT) score ≥15, and 25.0% had experienced ≥1 moderate/severe exacerbation in the past year. At week 24, GFF MDI improved morning pre-dose trough FEV1 versus GP MDI (least squares mean [LSM] difference [95% confidence interval (CI)]: 59 mL [43, 75]), FF MDI (65 mL [48, 81]), and placebo MDI (146 mL [125, 166]); all p < 0.0001. GFF MDI reduced the risk of a moderate/severe exacerbation by 18% (p = 0.0168), 15% (p = 0.0628), and 28% (p = 0.0012) compared with GP MDI, FF MDI, and placebo MDI, respectively. In general, exacerbation risk reduction with GFF MDI versus comparators was greater in subgroups of symptomatic patients (CAT ≥15) and those who had an exacerbation history, than in the pooled intent-to-treat population. The risk of CID was also lower with GFF MDI versus GP MDI (23% decrease), FF MDI (17%), and placebo MDI (49%); all p < 0.0001. All treatments were well tolerated, with no unexpected safety signals. CONCLUSIONS: This pooled analysis of the PINNACLE studies demonstrated that GFF MDI improved lung function and reduced the risk of exacerbations compared with monocomponents and placebo in patients with COPD. Exacerbation reductions with GFF MDI versus comparators were generally greater in patients with higher symptom burden and those with exacerbation history. TRIAL REGISTRATION: ClinicalTrials.gov NCT01854645, NCT01854658, and NCT02343458. Registered 13 May 2013 (NCT01854645, NCT01854658) and 6 January 2015 (NCT02343458).

Validation of a claims-based algorithm to identify patients with chronic thromboembolic pulmonary hypertension using electronic health record data.

This study aimed to validate an algorithm developed to identify chronic thromboembolic pulmonary hypertension (CTEPH) among patients with a history of pulmonary embolism. Validation was halted because too few patients had gold-standard evidence of CTEPH in the administrative claims/electronic health records database, suggesting that CTEPH is underdiagnosed.

Riociguat improves health-related quality of life for patients with pulmonary arterial hypertension: results from the phase 4 MOTION study.

Pulmonary arterial hypertension (PAH) is characterized by progressive dyspnea and exercise limitation and is associated with reduced health-related quality of life. Few clinical studies have evaluated the primary effects of treatment of PAH from the patient perspective. Here, we present the impact of riociguat on patient-reported outcomes (PROs) in treatment-naïve patients with PAH. MOTION (NCT02191137) was an open-label, phase 4 trial of riociguat monotherapy in treatment-naïve patients with PAH. The primary endpoint was the change in total score from baseline to Week 24 in the Living with Pulmonary Hypertension (LPH) questionnaire. The Short Form-12 Health Survey and Work Limitations Questionnaire 8 were also utilized to assess PROs. Other secondary endpoints included change from baseline in World Health Organization functional class (WHO FC), 6-min walk distance (6MWD), Modified Borg Dyspnea Scale, and safety. At week 24 (n = 66), the mean (standard deviation [SD]) total LPH score was 37.17 (24.61), for a mean (SD) change from baseline of -10.99 (22.51). At last visit, with week 24 imputed, the mean (SD) total score was 40.63 (28.38), for a mean (SD) change from baseline of -5.40 (27.8) (n = 75; P = 0.0484). Improvement in LPH questionnaire total score was observed by week 4 and was maintained through week 24. Improvements were observed in WHO FC, Modified Borg Dyspnea Scale, and accelerometer-measured 6MWD at week 24. Treatment with riociguat had a positive impact on PROs in treatment-naïve patients with PAH and was well tolerated, with a similar safety profile to that observed in placebo-controlled phase 3 trials.

Eugenics, genetics, and the minority group model of disabilities: implications for social work advocacy.

In the United States, genetic research, as well as policy and practice innovations based on this research, has expanded greatly over the past few decades. This expansion is indicated, for example, by the mapping of the human genome, an expansion of genetic counseling, and other biogenetic research. Also, a disability rights movement that in many ways parallels other "minority" rights campaigns has expanded. The coexistence of these developments poses intriguing challenges for social work that the profession has yet to address in a meaningful way. These issues are especially pertinent for social work professionals in the crucial role as advocates for marginalized populations. This article describes some ofthe concerns of disability rights activists relative to genetic innovations and goals as well as the instrumental role of the social work community in this important debate.

Important elements of the Americans With Disabilities Act for persons with diabetes.

Having diabetes can have profound implications for individuals in the workplace. Due to the increasing number of people who are diagnosed with this disease and the often complex treatment it requires, this issue continues to pose challenges for not only employees with this illness, but also for their employers. The 1990 Americans with Disabilities Act (ADA) was influential in promoting accommodations for and nondiscrimination against people with diabetes in the workplace. This article discusses 3 of the elements that can make it difficult for persons with diabetes to file a successful claim under the ADA. These important elements include employee disability status, the ability to perform essential job functions, and direct threat concerns.

The Americans with Disabilities Act: a decision tree for social services administrators.

The 1990 Americans with Disabilities Act has had a profound influence on social workers and social services administrators in virtually all work settings. Because of the multiple elements of the act, however, assessing the validity of claims can be a somewhat arduous and complicated task. This article provides a "decision tree" for administrators to assist with the evaluation of claims. This decision tree allows people who are considering the validity of an ADA claim to break the decision-making process into discrete steps that can be considered separately and sequentially. These steps include employee and disability status, employer knowledge of the disability, employee qualification for the job, the provision of accommodations, the adverse actions that may be included in a claim, valid employer rationales for adverse action, and the procedural elements required for a successful ADA claim. Issues that are important in each step are discussed.

Rosemary Kennedy: the importance of a historical footnote.

In most accounts of the Kennedy family, Rosemary, John F. Kennedy's eldest sister, has been discussed only in passing. In fact, there is much in Rosemary 's story that is instructive in regard to the effort families take to cope with disability, the impact of the social environment on such efforts, and the impact of a disabled member on the family as a whole. Rosemary's presence within the Kennedy home may have been a much more important component of the family' rise to prominence than most scholars appear to believe. This article describes Rosemary's place within the family, attempts by her parents and siblings to cope with and obfuscate her condition, and her possible impact on family dynamics.

People with cognitive disabilities: the Argument from Marginal Cases and social work ethics.

A primary argument used by animal rights advocates to engage the public in questioning our maltreatment of animals is the Argument from Marginal Cases (AMC). It is important that social workers are aware of this argument, because it has the potential to diminish our consideration of people with severe cognitive disabilities. This article provides a brief overview of the argument, followed by a description of the means by which people with cognitive disabilities have been denigrated over the past century through animalistic rhetoric and negative comparisons with animals. The "animalization" of marginalized groups of all types has often served to reinforce and justify dehumanizing treatment of group members. Questions related to the logic of the AMC are raised, and the importance of the argument for the social work community is discussed.

Gastroparesis after combined heart and lung transplantation.

GOALS: To determine the prevalence, severity, and outcome of gastroparesis after heart and lung transplantation (HLT). STUDY: Ten patients (five women; age range, 27-57 years) underwent HLT at Temple University Hospital from 1996 to 1999. The charts of these patients were reviewed, including results from gastric emptying scans and upper endoscopies. Symptoms were assessed with a standardized questionnaire. RESULTS: The indications for HLT included pulmonary hypertension in six patients, Eisenmenger syndrome in two, and dilated cardiomyopathy and congenital heart disease in two. Four patients died before the start of this clinical analysis. The six surviving patients constituted our study population. The patients' posttransplantation follow-up period ranged from 1.4 to 4.4 years (average, 2.6 years). Five patients (83%) were symptomatic with nausea, vomiting, and postprandial abdominal distension. Solid phase gastric emptying was delayed in all five patients with mean gastric retention of 93% at 2 hours (normal <50%). Patients generally did not respond to prokinetic agents. Four patients required pyloroplasty with J tube placement for symptom control, nutrition, and delivery of immunosuppressive medication. CONCLUSIONS: There is a high prevalence of symptomatic gastroparesis in patients after HLT. The gastroparesis is severe and often resistant to prokinetic agents.