Uncontrolled asthma across GINA treatment steps 2 - 5 in a large US patient cohort.

OBJECTIVE: Despite advances in treatment, asthma remains uncontrolled in many patients, with increased risk of exacerbation and associated healthcare resource utilization (HCRU). We describe patient characteristics, exacerbations, asthma control, and HCRU using GINA treatment step (GS) as a proxy for asthma severity. . METHODS: Using a large, US, health-claims database, 4 longitudinal cohorts of 517,738 patients in GS2-5, including a subgroup of patients with baseline eosinophil (EOS) counts, were analyzed retrospectively (study period 2010 - 2016). Index for each cohort was patients' first time entering the GS, determined by first claim of first regimen. Uncontrolled asthma was defined according to published criteria as a multi-dimensional measure that includes number of exacerbations. Key variables including, baseline characteristics, post-index exacerbations, and HCRU (all-cause and asthma-specific events) are summarized by descriptive statistics. RESULTS: Uncontrolled asthma was reported in 19.8% patients in GS2, 44.8% in GS3, 49.3% in GS4, and 58.6% in GS5. Annualized mean (SD) rates of exacerbation 12 months post-index generally increased across GS2-5 (0.26 [0.86], 0.32 [0.79], 0.36 [0.83], 0.29 [0.86], respectively). HCRU also increased with increasing GS, with higher HCRU among the uncontrolled cohort within each GS. In patients with EOS ≥300 cells/µL, uncontrolled asthma also increased with increasing GS (21.8%, 43.9%, 50.5%, 67.2% for GS2-5, respectively). CONCLUSIONS: This large database study provides real-world evidence of the substantial degree of uncontrolled asthma in US clinical practice across GS, supporting calls for better asthma management. Healthcare burden tends to increase with lack of control in all groups, highlighting the need for improved patient education, adherence, access, and treatment optimization.Supplemental data for this article can be accessed at publisher's website.

Correlations between FEV1 and patient-reported outcomes: A pooled analysis of 23 clinical trials in patients with chronic obstructive pulmonary disease.

BACKGROUND: In clinical trials of inhaled bronchodilators, chronic obstructive pulmonary disease (COPD) guidelines recommend that patient-reported outcomes (PROs) are assessed alongside lung function. How these endpoints are related is unclear. METHODS: Pooled longitudinal data from 23 randomised controlled COPD studies were analyzed (N = 23,213). Treatments included long-acting ß2 agonists, long-acting muscarinic antagonists (LABAs or LAMAs) and the LABA/LAMA combination QVA149. Outcome measures were Transition Dyspnoea Index (TDI) and St. George's Respiratory Questionnaire (SGRQ) scores, COPD exacerbation frequency and rescue medication use. Relationships between changes in trough forced expiratory volume in one second (ΔFEV1) and outcomes following treatment were assessed using correlations of data summaries and model-based analysis: generalized linear mixed-effect regression modelling to determine if ΔFEV1 could predict patient outcomes with different treatments. RESULTS: Mean age was 64 years, 73% were male, and most had moderate (45%) or severe (52%) disease. Statistically significant correlations were observed between ΔFEV1 and each outcome measure (exacerbations Rs = 0.05; rescue medication, SGRQ, TDI, r = 0.11-0.16; all p < .001). Patients with greater improvements in trough FEV1 had on average better SGRQ and TDI scores, fewer exacerbations, and used less rescue medication. For SGRQ and TDI scores, minimal clinically important differences were observed over the range of pooled ΔFEV1 values. Model-based predictions confirmed the treatment effect was partly explained by changes in FEV1 from baseline with improvements in PROs observed across all treatments when trough FEV1 improved. Across all endpoints active treatments were better than placebo (p < .0001), and LABA/LAMA treatment resulted in numerically better treatment outcomes than either monocomponent. CONCLUSIONS: These data suggest that FEV1 improvements post-bronchodilation correlate with PRO improvements. Further improvements in patient outcomes may be expected by maximizing lung function improvements. TRIAL REGISTRATION: Registration details for the 23 randomised controlled studies used in this pooled analysis are supplied in Additional File 4.

The association of lung function and St. George's respiratory questionnaire with exacerbations in COPD: a systematic literature review and regression analysis.

BACKGROUND: This study investigated the relationship between changes in lung function (as measured by forced expiratory volume in one second [FEV1]) and the St. George's Respiratory Questionnaire (SGRQ) and economically significant outcomes of exacerbations and health resource utilization, with an aim to provide insight into whether the effects of COPD treatment on lung function and health status relate to a reduced risk for exacerbations. METHODS: A systematic literature review was conducted in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials of adult COPD patients published in English since 2002 in order to relate mean change in FEV1 and SGRQ total score to exacerbations and hospitalizations. These predictor/outcome pairs were analyzed using sample-size weighted regression analyses, which estimated a regression slope relating the two treatment effects, as well as a confidence interval and a test of statistical significance. RESULTS: Sixty-seven trials were included in the analysis. Significant relationships were seen between: FEV1 and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.001); between FEV1 and moderate-to-severe exacerbations (time to first exacerbation, patients with at least one exacerbation, or annualized rate, p = 0.045); between SGRQ score and any exacerbation (time to first exacerbation or patients with at least one exacerbation, p = 0.0002) and between SGRQ score and moderate-to-severe exacerbations (time to first exacerbation or patients with at least one exacerbation, p = 0.0279; annualized rate, p = 0.0024). Relationships between FEV1 or SGRQ score and annualized exacerbation rate for any exacerbation or hospitalized exacerbations were not significant. CONCLUSIONS: The regression analysis demonstrated a significant association between improvements in FEV1 and SGRQ score and lower risk for COPD exacerbations. Even in cases of non-significant relationships, results were in the expected direction with few exceptions. The results of this analysis offer health care providers and payers a broader picture of the relationship between exacerbations and mean change in FEV1 as well as SGRQ score, and will help inform clinical and formulary-making decisions while stimulating new research questions for future prospective studies.

Psychometric evaluation of an electronic Asthma Symptom Diary for young children.

BACKGROUND: Patient-reported outcome measures that facilitate self-report by children are needed to reduce the bias of proxy report. We previously developed an electronic Pediatric Asthma Symptom Diary (ePASD) to assess the severity of daily asthma symptoms and proximal impacts in children aged 6-11 years with mild to severe asthma. The ePASD, administered via a digital application with visuals, sounds, and text, is uniquely designed to minimize the importance of reading skills on children's ability to self-report accurately. Here, we describe the ePASD's psychometric properties. METHODS: Ninety-one children aged 6-11 years with mild to severe asthma and their caregivers participated in 2 study visits, which consisted of training on the provisioned device and completing asthma-specific clinical outcome assessment (COA) questionnaires. The children self-completed the ePASD at home twice daily for 8 consecutive days. The scoring of the ePASD was guided by factor analyses, inter-item correlations, and internal consistencies. Reliability, discriminating ability, construct validity, and responsiveness were evaluated for ePASD items and candidate scores. RESULTS: All COAs included in the study-the ePASD, Asthma Control Questionnaire (ACQ), Childhood Asthma Control Test, Pediatric Asthma Quality of Life Questionnaire-Standardized (PAQLQ[S]), and global ratings-demonstrated that the children exhibited few asthma-related symptoms and impacts at all timepoints, and consequently, showed little change over time. Internal consistencies (all Cronbach's alphas ≥ 0.52) and test-retest reliabilities (all intraclass correlation coefficients ≥ 0.60) were largely satisfactory. Patterns of convergent and divergent correlations supported the construct validity of ePASD scores. The ePASD symptom scores correlated moderately to strongly with PAQLQ(S) Symptom scores (all correlations ≥ - 0.46) and with ACQ scores (all correlations ≥ 0.42), as predicted. Evidence of the discriminating ability of ePASD items and composite scores was demonstrated by known-groups analyses. CONCLUSIONS: The ePASD is a reliable and valid measure of asthma symptoms and proximal impacts in children aged 6-11 years with mild, moderate, or severe asthma. These results lay the psychometric groundwork for use of the ePASD in future clinical trials for the management of pediatric asthma. An ongoing pediatric asthma treatment trial is anticipated to provide evidence of the ePASD's responsiveness to change.

Impact of choice of inhalers for asthma care on global carbon footprint and societal costs: a long-term economic evaluation.

BACKGROUND: While effective asthma control medications reduce the burden of asthma, a significant subgroup of these treatments, namely metered-dose inhalers (MDIs), produce substantial greenhouse gas (GHG) emissions, thus contributing to climate change. This study quantified the global climate impact (i.e. carbon dioxide equivalent [CO2e] emissions) and costs of long-term status quo asthma inhaler use versus alternative scenarios substituting MDIs with propellant-free dry powder inhalers (DPIs). METHODS: Three scenarios were evaluated across 10-year (2020-2030) and 50-year (2020-2070) time horizons: A (status quo inhaler use), B and C (2% and 5% year-over-year substitution of MDIs with DPIs, respectively). Global inhaler volumes and costs at baseline were sourced from IQVIA, then projected using UN and WHO trends in per capita GDP, urbanization, and asthma population growth. Inhaler spending was assumed to fall by 90% following generic entry in 2030. The carbon footprint per inhaler and health damage factors for disability-adjusted life years (DALYs) were derived from literature. The US government's central and high-impact estimates for the social cost of carbon (SCC) were used to calculate emissions costs. RESULTS: Over 50 years, scenario A resulted in 826 million tonnes of CO2e emissions globally, with an associated SCC between 21% and 65% of the projected global spending on asthma inhalers. In comparison, CO2e emissions were reduced by 38% and 58% in Scenarios B and C, respectively, and DALYs improved by 33 and 51%. Depending on SCC estimates, Scenarios B and C increased global costs by 7.3% and 16.5%, respectively (central SCC), or decreased costs by 4.2% and 2.6% (high-impact SCC) versus Scenario A. Over 10 years, Scenario A resulted in 97 million tonnes of CO2e emissions globally, with an associated SCC between 4.4% and 12.2% of projected spending. In comparison, Scenarios B and C were associated with 12% and 24% reductions in CO2e emissions and improvements in DALYs by 11.5% and 22.7%, respectively. CONCLUSIONS: Global efforts by environmental and health-policy decision-makers to substitute currently available MDIs with DPIs for asthma control would result in substantial reductions in GHG emissions with manageable costs, or potential cost savings, depending on the SCC. Policies that decrease use of MDIs warrant global attention.

Carbon footprint and associated costs of asthma exacerbation care among UK adults.

INTRODUCTION: Asthma exacerbations are a primary driver of costs and health impacts from asthma. Despite research suggesting that asthma care has a disproportionate carbon footprint, emissions costs are not considered when evaluating its societal burden. To advance the understanding of greenhouse gas (GHG) emissions associated with asthma, we estimated the carbon footprint and associated costs of asthma exacerbation care by severity level among UK adults. METHODS: Guidelines for asthma exacerbation treatment in UK adults were reviewed by severity level: mild, moderate, and severe/life-threatening. Components of care for each severity were evaluated for GHG emission potential and key drivers were identified. Carbon dioxide equivalent (CO2e) emissions of drivers were sourced from published literature and combined to estimate the carbon footprint per exacerbation, by severity level. Emissions were scaled up to the annual UK adult population based on the annual number of exacerbations at each severity. Costs associated with emissions were estimated using the UK government's 2020 nontraded price of carbon, at £71 per tonne CO2e (tCO2e). RESULTS: Overall, emissions drivers for exacerbations were medical services, including patient-travel, and quick-relief inhalers. The annual number of mild, moderate, and severe/life-threatening asthma exacerbations among UK adults were 118.9 M, 5.5 M, and 2.4 M. Associated annual carbon footprints were estimated to be 83,455 tCO2e, 192,709 tCO2e, and 448,037 tCO2e for mild, moderate, and severe/life-threatening exacerbations, respectively, with a total of 724,201 tCO2e. Total annual emissions costs from exacerbation care were £51.3 M; £5.9 M, £13.6 M, and £31.7 M for mild, moderate, and severe/life-threatening exacerbations, respectively. CONCLUSION: GHG emissions from asthma exacerbation management were the highest for severe/life-threatening events, followed by moderate exacerbations. Treatment to reduce the severity and occurrence of exacerbations, such as effective, long-term control therapy via lower-emission dry powder inhalers (DPIs), can help mitigate asthma care emissions. For mild exacerbations, the use of DPIs can eliminate associated emissions.

Development and content validation of a self-completed, electronic Pediatric Asthma Symptom Diary.

BACKGROUND: Childhood asthma is an important unmet need. To date, patient-reported outcome measures (PROMs) for children with asthma have used a combination of caregiver or proxy-reported and self-reported measures. No comprehensive measure is available to assess the severity and impact of daytime and nighttime asthma symptoms and rescue medication use for self-completion by children aged 6-11 years. This study aimed to develop a novel, interactive, electronic Pediatric Asthma Symptom Diary (ePASD) measuring self-reported key symptom severity and proximal impacts of asthma in young children with varying reading ability and disease severity, consistent with US Food and Drug Administration (FDA) PRO guidance and the International Society for Health Economics and Outcomes Research (ISPOR) good research practices. METHODS: A targeted literature review and clinician interviews were undertaken to characterize symptoms and impacts experienced by children with mild-to-severe asthma. Concept elicitation interviews (CEIs) were conducted with 44 children and their caregivers (30 US; 14 UK). Following item and digital application development, the ePASD was assessed for relevance, understanding, and interpretability through cognitive debriefing interviews (CDIs) with 21 US children. Face validity/translatability assessments were also performed. RESULTS: Key measurement concepts included cough, wheeze, difficulty breathing, chest tightness/discomfort, nighttime awakening, and daytime activity limitations. Concept saturation was reached during CEIs for primary asthma-related daytime and nighttime symptoms and core impacts. Most CDI participants found the ePASD items clear, understandable, and comprehensive. Standardized training is anticipated to facilitate reliable child self-report. CONCLUSION: The ePASD, a novel PROM for children aged 6-11 years with asthma, uses an innovative multimedia approach and has been developed in accordance with FDA PRO guidance and ISPOR good research practices, directly capturing the child's self-reported asthma symptoms, impacts on daily activities and nighttime awakening, and rescue medication use.

Cost-Effectiveness of Once-Daily, Single-Inhaler Indacaterol Acetate/ Glycopyrronium Bromide/ Mometasone Furoate in Patients with Uncontrolled Moderate-to-Severe Asthma in Canada.

PURPOSE: We evaluated the cost-effectiveness of high-dose indacaterol acetate (IND)/glycopyrronium bromide (GLY)/mometasone furoate (MF) (150/50/160 µg, once daily) compared with high-dose salmeterol/fluticasone (SAL/FLU; 50/500 µg, twice daily)+tiotropium (TIO; 5 µg, once daily) (SAL/FLU+TIO) and with high-dose SAL/FLU (50/500 µg, twice daily) for the treatment of inadequately controlled moderate-to-severe asthma. PATIENTS AND METHODS: A Markov model estimated the incremental cost-effectiveness ratio of treatment with high-dose IND/GLY/MF compared with SAL/FLU+TIO and high-dose IND/GLY/MF compared with SAL/FLU. The model included three health states (day-to-day symptoms without exacerbations, day-to-day symptoms with exacerbations, and death) with a 4-week cycle length. A lifetime time horizon was used. Exacerbation rates and utility values were derived from ARGON and IRIDIUM clinical trials. Canadian dollars (CAD$, 2020) were applied. RESULTS: IND/GLY/MF was the less costly and more effective treatment strategy compared with SAL/FLU+TIO and SAL/FLU in the base-case analyses. IND/GLY/MF had lower costs (CAD $33,501 versus CAD $50,907) and higher quality-adjusted life-years (QALYs) (18.37 versus 18.06 QALYs) compared with SAL/FLU+TIO. Compared with SAL/FLU, IND/GLY/MF had lower costs (CAD $33,408 versus CAD $36,577) and higher QALYs (19.33 versus 19.04 QALYs). IND/GLY/MF was the most cost-effective option in all scenarios tested. CONCLUSION: IND/GLY/MF was cost-effective at a willingness-to-pay threshold of CAD $50,000/QALY in patients with uncontrolled, moderate-to-severe asthma versus SAL/FLU+TIO and SAL/FLU in the base case and all scenarios tested.

Physician-Patient Concordance in the Assessment of Asthma Control.

BACKGROUND: Discordance between physicians' and patients' perceptions of asthma control may negatively impact symptom control, treatment, and outcomes. OBJECTIVE: To evaluate concordance between physicians' and patients' perceptions of overall asthma control and the association between perceived overall control and individual components of control. METHODS: U.S. survey data (Dec 2015-Feb 2016; Apr-Aug 2018) from the Respiratory Disease Specific Programme were analyzed. Physicians recorded patient disease characteristics and their perception of patients' asthma control. Patients' perception of control was assessed using the Asthma Control Test; responses were compared with level of symptom control per the Global Initiative for Asthma criteria and Work Productivity and Impairment questionnaire responses. Agreement and association were assessed by weighted kappa (κ) and Spearman rho (ρ), respectively. RESULTS: The study included 1,288 patients. Concordance between physician-perceived and patient-perceived asthma control in the prior 4 weeks was moderate (κ = 0.4951). Association between physicians' overall perception of asthma control and patients' overall Asthma Control Test score was also moderate (ρ = 0.5450). However, 61.5% of patients with self-reported, well-controlled asthma had shortness of breath 1 to 2 times/wk, 45.6% had 1 to 2 night-time awakenings/wk, and patients reported a mean (SD) daily activity impairment of 17.5% (16.2%). Only 21.8% of patients with self-reported, well-controlled asthma were classified as such by Global Initiative for Asthma symptom criteria. CONCLUSIONS: Patients' self-assessment of overall control does not accurately characterize the true level of control; thus, patients and physicians may benefit from working together to assess the individual components of asthma control to achieve better disease management, treatment decisions, and improved outcomes.

Disease burden and cost of hidradenitis suppurativa: a retrospective examination of US administrative claims data.

OBJECTIVES: Hidradenitis suppurativa (HS) causes substantial morbidity and quality-of-life impairment. We examined demographic/clinical characteristics of patients with HS and treatment patterns, prevalence and healthcare resource utilisation/expenditures related to HS in the real-world. DESIGN: Retrospective claims data of MarketScan Commercial, Medicare Supplemental and Medicaid databases (2009-2014). SETTING: USA. PARTICIPANTS: Patients aged ≥12 years with ≥3 non-diagnostic outpatient or inpatient claims with an HS diagnosis code and ≥12 months continuous enrolment with medical and pharmacy benefits before (preindex) and after (postindex) the earliest diagnosis of HS (index) were included. RESULTS: There were 11 325 Commercial/Medicare patients (mean age 37.4 years) and 5164 Medicaid patients (mean age 28.3 years). HS was more common in Medicaid than Commercial/Medicare patients (0.301% and 0.098%, respectively, in 2014). Cellulitis and psychiatric disorders were the most common comorbidities and oral antibiotics and narcotics were the most frequently prescribed drugs preindex, with ≥10% increase postindex in both populations. HS-related inpatient costs decreased while outpatient costs increased from preindex to postindex. Medicaid patients had several risk factors that may be associated with poor outcomes (eg, high rates of prescription pain medication use, comorbidities, drug discontinuation/interruption/holiday, emergency department (ED) visits and hospitalisation). CONCLUSIONS: Commercial/Medicare and Medicaid HS beneficiaries experience high comorbidity burden but use different treatment modalities to manage HS. Results suggest a substantial unmet need exists among this patient population, with Medicaid patients experiencing a particularly high burden of disease and expensive healthcare resource utilisation.

Association Between Pulmonary Function and Asthma Symptoms.

BACKGROUND: FEV1 as a percentage of predicted (FEV1%pred) is commonly measured in asthma clinical studies; however, reports vary on its association with asthma control instruments evaluating symptoms. OBJECTIVE: Assess the association between FEV1%pred and Asthma Control Questionnaire (ACQ) scores in a managed-care population with persistent asthma. METHODS: Retrospective analysis of survey responses and spirometry results of patients (aged ≥12 years) with persistent asthma from the Observational Study of Asthma Control and Outcomes was done. Eligible patients received 4 identical surveys including the 5-item ACQ (ACQ-5)/6-item ACQ (ACQ-6) and completed spirometry in parallel. Longitudinal analyses, comparisons of change over time, and fixed- and random-effects regression analyses were conducted, with/without adjustment for covariates. RESULTS: There were 1748 survey responses with valid spirometry results. In unadjusted models, coefficients for ACQ-5/ACQ-6 scores were not statistically significant and coefficient of determination (R2) was low (0.03). When adjusted for covariates, ACQ-5 and ACQ-6 scores were significantly associated with FEV1%pred (P < .001) and R2 increased to 0.11 and 0.12, respectively. In adjusted models, every 1-point increase in ACQ-5 and ACQ-6 scores was associated with a 1.7% and 1.9% decrease, respectively, in FEV1%pred. Change in FEV1%pred and change in ACQ-5/ACQ-6 scores were not significantly associated in regressions with/without covariates. CONCLUSIONS: The weak and statistically insignificant association between FEV1%pred and ACQ-5/ACQ-6 scores in unadjusted models suggests a high degree of unexplained variation between these measures. Results support the use of both symptoms and pulmonary function, rather than relying on one measure alone, to assess asthma control in clinical care and outcomes studies.

Cost-effectiveness of twice-daily indacaterol/glycopyrrolate inhalation powder for the treatment of moderate to severe COPD in the US.

BACKGROUND: Indacaterol 27.5 µg/glycopyrrolate 15.6 µg (IND/GLY 27.5/15.6 µg) inhalation powder, a twice-daily, fixed-dose combination of a long-acting beta2-agonist (LABA) and a long-acting antimuscarinic antagonist (LAMA), is indicated in the US for long-term maintenance treatment of airflow obstruction in patients with COPD. The safety and efficacy of IND/GLY 27.5/15.6 µg have been established, but cost-effectiveness is not yet known. This study compared the cost-effectiveness of IND/GLY 27.5/15.6 µg with other long-acting COPD maintenance therapies. METHODS: A Markov model was constructed from the US payer perspective. Health states were defined as mild (post-bronchodilator FEV1 ≥80% of predicted), moderate (50% ≤FEV1 <80% of predicted), severe (30% ≤FEV1 <50% of predicted), and very severe (FEV1 <30% of predicted) COPD. Patients entering the model transitioned through health states based on placebo-adjusted change from baseline in trough FEV1 for each comparator at week 12. Comparators included other US Food and Drug Administration-approved LABA/LAMA fixed-dose combinations as well as commonly prescribed LAMA and LABA/inhaled corticosteroid agents. One-way and probabilistic sensitivity analyses were conducted to test the model assumptions and the overall robustness of the results. RESULTS: Using the model, IND/GLY 27.5/15.6 µg treatment for 12 weeks resulted in total costs of US $23,375 vs US $9,365 for placebo. Compared with placebo, IND/GLY 27.5/15.6 treatment resulted in the highest improvement in FEV1 across all comparators and the lowest cost per decline in 100 mL FEV1. IND/GLY 27.5/15.6 µg was also among the most cost-effective treatment option as measured by St George's Respiratory Questionnaire response rate, at US $3,518 per additional responder at 12 weeks compared with placebo. In addition, IND/GLY 27.5/15.6 µg had the lowest cost per severe exacerbation avoided vs placebo across all comparators (US $87,686). CONCLUSION: This model, developed from the US payer perspective with a 5-year time horizon, found IND/GLY 27.5/15.6 µg to be a cost-effective treatment option for patients with moderate to severe COPD.

Health Status of Patients With Chronic Obstructive Pulmonary Disease by Symptom Level.

Background: Despite receiving treatment, patients with chronic obstructive pulmonary disease (COPD) often continue to experience symptoms that impact their health status. We determined the relationship between overall symptom burden and health status, and assessed the treatments patients were receiving. Methods: Data from 3 cross-sectional surveys of U.S. patients with COPD (2011-2013) were analyzed. Patients receiving inhaled COPD treatment for ≥3 months completed the COPD Assessment Test (CAT) symptom burden and respiratory health status measure, EuroQol 5-dimension (EQ-5D-3L) general health status questionnaire, and Jenkins Sleep Evaluation Questionnaire (JSEQ). CAT scores were used to identify high- (CAT ≥24) and low-symptom patients (CAT <24), who were matched using 1:1 propensity score matching with replacement. Match balance was assessed with standardized mean differences. EQ-5D-3L and JSEQ scores, and current treatment were compared between groups post-matching. Sensitivity was assessed with Rosenbaum bounds. Results: A total of 638 patients were included. Compared with low-symptom patients, high-symptom patients had worse health status and greater sleep disturbance by EQ-5D utility index (0.85 versus 0.71, respectively; p<0.0001) and JSEQ scores (3.73 versus 7.35, respectively; p<0.0001). High-symptom patients were prescribed single-maintenance bronchodilators ± inhaled corticosteroids (46.0%), triple therapy (40.5%), and short-acting therapy only (8.2%). Results were robust and insensitive to unobserved confounders. Conclusions: Increased COPD symptom burden is associated with worse general health status in patients receiving COPD treatment. High-symptom patients frequently received single inhaled medication. The results suggest that health care providers should monitor and tailor therapy, based on level of symptom burden to improve symptom control and health status.

Burden of illness among patients with fragile X syndrome (FXS): a Medicaid perspective.

BACKGROUND: Fragile X syndrome (FXS) is an inherited intellectual disability that imposes a substantial clinical and humanistic burden on patients and caregivers. This study aimed to quantify the incremental burden of illness following FXS diagnosis in Medicaid populations. METHODS: A retrospective matched-cohort study was conducted using FL, NJ, MO, IA, and KS Medicaid claims (1997-2012). Patients with FXS were matched 1:5 to a comparison group without FXS, based on age, gender, state, and continuous Medicaid coverage. Healthcare resource utilization and costs were compared among cohorts over 1 year following first diagnosis. RESULTS: Overall, 697 patients with FXS were matched to 3485 non-FXS patients. Median age was 12.0 years; 82% were male. Newly diagnosed FXS patients were younger (median age: 7.0 years). During the follow-up, patients with FXS had significantly higher medication use, medical procedure use, medical specialist visits, and associated costs than the non-FXS comparison group. One-fourth of FXS patients filled prescriptions for stimulants, antipsychotics, or anticonvulsants; 25% of patients with FXS had speech and language therapy and 39% had physical therapy (versus 9%, 4% and 8%, respectively, for the comparison group). At least 44% of FXS patients visited a neurologist, cardiologist, otolaryngologist, or gastroenterologist; 92% of patients with FXS had an outpatient visit, 35% had an emergency room visit, and 34% used home services (compared to 31%-32%, 64%, 27%, and 10%, respectively, for the comparison group) (all p < 0.05). Patients with FXS had an incremental annual total healthcare cost of $33,409 (2012$) per person relative to the comparison group, while newly diagnosed FXS patients had incremental total annual healthcare costs of $17,617 (2012$) per person. CONCLUSIONS: Both established and newly diagnosed FXS were associated with significantly increased use of multiple medications and medical services, and increased healthcare costs. Treatments that could help reduce this disease burden are urgently needed.

Impact of lung function on exacerbations, health care utilization, and costs among patients with COPD.

OBJECTIVE: To evaluate the impact of lung function, measured as forced expiratory volume in 1 second (FEV1) % predicted, on health care resource utilization and costs among patients with COPD in a real-world US managed-care population. METHODS: This observational retrospective cohort study utilized administrative claim data augmented with medical record data. The study population consisted of patients with one or more medical claims for pre- and postbronchodilator spirometry during the intake period (July 1, 2012 to June 30, 2013). The index date was the date of the earliest medical claim for pre- and postbronchodilator spirometry. Spirometry results were abstracted from patients' medical records. Patients were divided into two groups (low FEV1% predicted [,50%] and high FEV1% predicted [≥50%]) based on the 2014 Global Initiative for Chronic Obstructive Lung Disease report. Health care resource utilization and costs were based on the prevalence and number of discrete encounters during the 12-month postindex follow-up period. Costs were adjusted to 2014 US dollars. RESULTS: A total of 754 patients were included (n=297 low FEV1% predicted group, n=457 high FEV1% predicted group). COPD exacerbations were more prevalent in the low FEV1% predicted group compared with the high group during the 12-month pre- (52.5% vs 39.6%) and postindex periods (49.8% vs 36.8%). Mean (standard deviation) follow-up all-cause and COPD-related costs were $27,380 ($38,199) and $15,873 ($29,609) for patients in the low FEV1% predicted group, and $22,075 ($28,108) and $10,174 ($18,521) for patients in the high group. In the multivariable analyses, patients in the low FEV1% predicted group were more likely to have COPD exacerbations and tended to have higher COPD-related costs when compared with patients in the high group. CONCLUSION: Real-world data demonstrate that patients with COPD who have low FEV1% predicted levels use more COPD medications, have more COPD exacerbations, and incur higher COPD-related health care costs than those with high FEV1% predicted levels.