Advancing assessment of asthma control with a composite tool: The Asthma Impairment and Risk Questionnaire.

BACKGROUND: National and international asthma guidelines and reports do not include control tools that combine impairment assessment with exacerbation history in one instrument. OBJECTIVE: To analyze the performance of the composite Asthma Impairment and Risk Questionnaire (AIRQ) in assessing both domains of control and predicting exacerbation risk compared with the Global Initiative for Asthma (GINA) 4-question symptom control tool (GINA SCT), Asthma Control Test (ACT), and physician expert opinion (EO) informed by GINA SCT responses and appraisal of GINA-identified risk factors for poor asthma outcomes. METHODS: Multivariable logistic regressions evaluated AIRQ and GINA SCT as predictors of ACT. McNemar's test compared the proportion of patients categorized at baseline as completely or well-controlled by each assessment but with current impairment or previous-year and subsequent-year exacerbations. RESULTS: The analysis included 1064 patients aged 12 years or older; mean (SD) age 43.8 years (19.3); 70% female; 79% White; and 6% Hispanic or Latino. AIRQ and GINA SCT were highly predictive of ACT well-controlled vs not well-controlled and very poorly controlled (receiver operator characteristic area under curve AIRQ = 0.90, GINA SCT = 0.86, P = .03 AIRQ vs GINA SCT) and ACT very poorly controlled vs well-controlled and not well-controlled asthma (receiver operator characteristic area under curve AIRQ = 0.91, GINA SCT = 0.87, P = .01 AIRQ vs GINA SCT). AIRQ rated fewer patients as having completely or well-controlled asthma who had current impairment (P < .01) or with previous-year and subsequent-year exacerbations (P < .001) than did GINA SCT, ACT, and EO. CONCLUSION: AIRQ performs better in assessing both domains of current control and predicting exacerbation risk than do control tools and EO informed by GINA SCT and risk factors for poor asthma outcomes.

Assessing meaningful change in the Asthma Impairment and Risk Questionnaire.

BACKGROUND: The Asthma Impairment and Risk Questionnaire (AIRQ) is a 10-item, yes/no, equally weighted control tool. Lower scores indicate better control. Moreover, 7 impairment items reflect previous 2-week symptoms, and 3 risk items assess previous 12-month exacerbations. The Follow-up AIRQ for use between annual assessments has a 3-month recall period for exacerbation items. OBJECTIVE: To evaluate the responsiveness of the AIRQ over time and identify a minimal important difference (MID). METHODS: The AIRQ longitudinal study data were analyzed from patients with asthma aged 12 years and older. Anchor-based methods assessed differences in AIRQ scores relative to Patient Global Impression of Change, the accepted MIDs for St. George's Respiratory Questionnaire and Asthma Control Test, and exacerbation occurrence over 12 months. Baseline and 12-month data reflected 12-month recall AIRQ scores; Follow-up AIRQ scores were used for 3-, 6-, and 9-month analyses. RESULTS: A total of 1070 patients were included. The Patient Global Impression of Change rating of "much improved" was associated with AIRQ mean score changes from baseline to months 3, 6, 9, and 12 of -2.0, -1.9, -1.9, and -1.8, respectively. The mean AIRQ score change among patients who met the St. George's Respiratory Questionnaire MID (≥4-point decrease) was -1.8 at 6 and 12 months. The AIRQ mean scores decreased from baseline by -2.2 to -2.5 points at months 3, 6, 9, and 12 for patients who met the Asthma Control Test MID (≥ 3-point increase). A 2-point higher baseline AIRQ score was associated with a 1.7 odds ratio of 12-month exacerbation occurrence (95% CI, 1.53-1.89). CONCLUSION: A change score of 2 is recommended as the AIRQ MID.

The Asthma Impairment and Risk Questionnaire enhances the assessment of asthma control.

BACKGROUND: Asthma control is often overestimated in routine practice, and despite advances in the understanding of immunopathology and the availability of new precision therapies, the burden of disease remains unacceptably high. OBJECTIVE: To compare the performance of the Asthma Impairment and Risk Questionnaire (AIRQ) with patient and physician assessments and the Asthma Control Test (ACT) in identifying asthma control. METHODS: Baseline data from a longitudinal study of the AIRQ were analyzed. Patients with asthma in the United States aged 12 years and older followed in 24 specialty practices and 1 specialty-affiliated primary care clinic were enrolled between May and November 2019. At entry, participants completed AIRQ and ACT, and participants and physicians completed 5-point Likert scale assessments of control. RESULTS: A total of 1112 participants were enrolled (mean [SD] age = 43.9 [19.3] years, 70% of the female sex, 78% White). Overall, 62% of participants rated themselves as well- or completely controlled, and 54% were rated comparably by physicians. The ACT classified 49% of participants as well-controlled, with 35% similarly categorized by AIRQ. Previous-year exacerbations were experienced by 32% of participants who self-rated as well- or completely controlled, 30% who were rated as well- or completely controlled by physicians, and 29% assessed as well-controlled by ACT, but only 15% of those classified as well-controlled by AIRQ. CONCLUSION: The burden of asthma is substantial in patients cared for by asthma specialists, and asthma control is overestimated by patients, physicians, and the symptom-based ACT. The AIRQ assesses risk in addition to symptom control and may serve to improve asthma control determination by assessing previous exacerbations.

Evaluating construct validity of the Asthma Impairment and Risk Questionnaire using a 3-month exacerbation recall.

BACKGROUND: Recurrent assessment of asthma control is essential to evaluating disease stability and intervention impacts. An assessment that can be administered between annual clinic visits is needed. The Asthma Impairment and Risk Questionnaire (AIRQ) is a cross-sectionally validated, 10-item, yes or no, composite control tool evaluating previous 2-week symptoms and previous 12-month exacerbations. OBJECTIVE: To evaluate the construct validity of the AIRQ using a 3-month recall period for exacerbation-based risk questions and retaining the 2-week recall for symptom-based impairment items. METHODS: At baseline, patients completed the AIRQ with 12-month recall exacerbation items, Asthma Control Test (ACT), St. George's Respiratory Questionnaire (SGRQ), and global self-assessments of asthma risk, control, and symptom severity. Patient-reported exacerbations were captured monthly. The AIRQ with 3-month recall exacerbation items, ACT, and global self-assessments was administered at months 3, 6, and 9, and SGRQ at month 6. RESULTS: A total of 1112 patients aged 12 years or older were enrolled (mean [SD] age, 43.9 [19.5] years). The AIRQ and each administration of the AIRQ with 3-month recall exacerbation items classified asthma control similarly to an ACT plus exacerbation validation standard. For both AIRQ versions, SGRQ scores were higher with worsening asthma control (P < .001). At months 3, 6, and 9, worse AIRQ control levels were associated with higher proportions of patients with 1 or more and 2 or more exacerbations in the previous 3 months and patient global self-assessments indicating greater asthma morbidity (all P < .001). CONCLUSION: The AIRQ using exacerbation risk items with a 3-month recall period exhibits construct validity for classifying current asthma control and can be administered between annual AIRQ assessments.

Current practice patterns, challenges, and educational needs of asthma care providers in the United States.

OBJECTIVE: For severe, uncontrolled asthma (SUA), a gap exists between recent scientific advances and their incorporation into clinical practice. Using a Knowledge-to-Action Framework, new knowledge can be translated into evidence-based interventions to improve outcomes. The AstraZeneca U.S. PRECISION initiative aims to apply this Framework to improve recognition and management of SUA. The study objective was to identify factors contributing to gaps in care for patients with SUA. Results from a needs assessment survey of U.S. pulmonologists and allergists/immunologists were assessed within the Knowledge-to-Action Framework to advance bench-to-bedside care. METHODS: Pulmonologists and allergists/immunologists from across the United States were invited to complete a customized, quantitative severe asthma survey in person at the 2017 American Thoracic Society annual meeting or via the Internet. Responses were summarized descriptively, and chi-squared tests evaluated associations between variables of interest. RESULTS: Overall, 140 U.S. providers responded, most of whom were pulmonologists (84%). Most (60%) practiced in a community-based setting; 40% practiced at an academic medical center. Key challenges to providing care for patients with severe asthma included insurance company requirements and identification of the pathophysiology of an individual patient's severe asthma. Traditional measures of asthma-related morbidity were ranked as highly important by significantly more respondents compared with assessment of biomarkers (p < 0.0001). Respondents generally valued online virtual self-education. CONCLUSIONS: Survey results identified unmet needs for the identification and management of patients with SUA and opportunities to improve patient outcomes through evidence-based management of SUA, including testing for biologic eligibility and subsequent use of biologic therapies.

Efficacy of adjunctive aripiprazole in patients with major depressive disorder whose symptoms worsened with antidepressant monotherapy.

INTRODUCTION: Efficacy of depression treatments, including adjunctive antipsychotic treatment, has not been explored for patients with worsening symptoms after antidepressant therapy (ADT). METHODS: This post-hoc analysis utilized pooled data from 3 similarly designed, randomized, double-blind, placebo-controlled trials that assessed the efficacy, safety, and tolerability of adjunctive aripiprazole in patients with major depressive disorder with inadequate response to ADT. The studies had 2 phases: an 8-week prospective ADT phase and 6-week adjunctive (aripiprazole or placebo) treatment phase. This analysis focused on patients whose symptoms worsened during the prospective 8-week ADT phase (worsening defined as >0% increase in Montgomery-Åsberg Depressive Rating Scale [MADRS] Total score). During the 6-week, double-blind, adjunctive phase, response was defined as ≥50% reduction in MADRS Total score and remission as ≥50% reduction in MADRS Total score and MADRS score ≤10. RESULTS: Of 1065 patients who failed to achieve a response during the prospective phase, 160 exhibited worsening of symptoms (ADT-Worseners), and 905 exhibited no change/reduction in MADRS scores (ADT-Non-worseners). Response rates for ADT-Worseners at endpoint were 36.6% (adjunctive aripiprazole) and 22.5% (placebo). Similarly, response rates at endpoint for ADT-Non-worseners were 37.5% (adjunctive aripiprazole) and 22.5% (placebo). Remission rates at endpoint for ADT-Worseners were 25.4% (adjunctive aripiprazole) and 12.4% (placebo). For ADT-Non-worseners, remission rates were 29.9% (adjunctive aripiprazole) and 17.4% (placebo). CONCLUSION: These results suggest that adjunctive aripiprazole is an effective intervention for patients whose symptoms worsen during antidepressant monotherapy. The results challenge the view that benefits of adjunctive therapy with aripiprazole are limited to partial responders to ADT.

How well do clinicians and patients agree on depression treatment outcomes? Implications for personalized medicine.

OBJECTIVE: In order to inform outcomes assessments in personalized medicine research, we evaluated the level of agreement between self-reported (SR) and clinician-rated (CR) measures of depression severity before and after treatment with an antidepressant medication. METHODS: We pooled data from three trials (totaling 2075 patients) assessing the efficacy of antidepressant monotherapy in major depressive disorder. Differences between CR (17-item Hamilton Rating Scale for Depression [HAM-D17]) and SR (30-item Inventory of Depressive Symptomatology-Self-Rated) scale scores were used to determine concordance between CR-SR ratings. The effect of anxiety (HAMD17 anxiety-somatization subscale score ≥7) on SR-CR agreement was also assessed. RESULTS: The CR-SR scale agreement was good for response (κ = 0.64) and moderate for remission (κ = 0.57). Patients who rated their depression as less severe than the clinician were significantly more likely to respond to treatment than over-reporters (odds ratio = 1.62; 95% confidence interval: 1.17-2.25). Although anxiety did not impact the level of agreement, among patients with SR-CR discordance, high anxiety was associated with over-reporting of depression severity. CONCLUSION: The levels of disagreement for response and remission were too high for CR and SR scales to be considered interchangeable for research on patient-level outcomes. Anxiety does not meaningfully impact SR-CR agreement.

Validation of the Onset of Effect Questionnaire in Participants With Chronic Obstructive Pulmonary Disease.

Background: Patient perception of medication onset of effect is important for adherence. Although the Onset of Effect Questionnaire (OEQ) has been validated in patients with asthma, it has not been evaluated in patients with chronic obstructive pulmonary disease (COPD). This study evaluated the COPD-OEQ in patients with COPD. Methods: Two analyses (qualitative and quantitative) were conducted to assess the content validity and psychometric properties of the COPD-OEQ in participants with COPD. In the qualitative analysis, interviews assessed content validity by concept elicitation (CE) and cognitive interviewing (CI). CE included questions to understand patient experience related to onset of medication effect. CI included completion of the COPD-OEQ and assessment of the COPD-OEQ items, response options, and instructions. During the 2-week quantitative analysis, 2 versions of the COPD-OEQ (Weekly and Daily) were administered to assess test-retest reliability, construct validity, and known-groups validity. Results: The qualitative analysis demonstrated that 3 of the 5 COPD-OEQ items were relevant and understood as intended. Qualitative findings demonstrated inconsistent evidence that the COPD-OEQ Weekly and Daily were reliable and valid measures in participants with COPD. Test-retest reliability was observed for the COPD-OEQ Weekly and Daily; however, construct validitywas weak and demonstrated inconsistent correlations among COPD-OEQ items. Overall, known-groups validity was not demonstrated. Conclusion: The weak evidence from the quantitative analysis of the COPD-OEQ Weekly and Daily tools does not support use of the OEQ in general COPD. The study supports the content validity for the assessment of perceived onset of effect in patients with COPD.

Impact of Clinical Characteristics and Biomarkers on Asthma Impairment and Risk Questionnaire Exacerbation Prediction Ability.

BACKGROUND: Complex models combining impairment-based control assessments with clinical characteristics and biomarkers have been developed to predict asthma exacerbations. The composite Asthma Impairment and Risk Questionnaire (AIRQ) with adjustments for demographics (age, sex, race, and body mass index) predicts 12-month exacerbation occurrence similarly to these more complex models. OBJECTIVE: To examine whether AIRQ exacerbation prediction is enhanced when models are adjusted for a wider range of clinical characteristics and biomarkers. METHODS: Patients aged 12 years and older completed monthly online surveys regarding exacerbation-related oral corticosteroid use, emergency department or urgent care visits, and hospitalizations. Univariate logistic regressions to predict exacerbations were performed with sociodemographics, comorbidities, exacerbation history, lung function, blood eosinophils, IgE, and FeNO. Significant (P ≤ .05) variables were included in multivariable logistic regressions with and without AIRQ control categories to predict 12-month exacerbations (log odds ratio [95% Wald confidence interval]). Model performances were compared. RESULTS: Over 12 months, 1,070 patients (70% female; mean [SD] age, 43.9 [19.4] years; 22% non-White; body mass index [SD], 30.6 [8.7]) completed one or more survey (mean [SD], 10.5 [2.8] surveys). In the multivariable analysis, AIRQ control category adjusted for significant clinical characteristics and biomarkers was predictive of one or more exacerbations: odds ratio (95% CI) not well-controlled versus well-controlled: 1.93 (1.41-2.62), very poorly controlled versus well-controlled: 3.81 (2.65-5.47). Receiver operating characteristic area under the curve (AUC) for this more complex model of exacerbation prediction (AUC = 0.72) did not differ from AIRQ (AUC = 0.70). Models with AIRQ performed better than those without AIRQ (AUC = 0.67; P < .05). CONCLUSION: Costly and time-consuming complex modeling with clinical characteristics and biomarkers does not enhance the strong exacerbation prediction ability of AIRQ.

Sodium Zirconium Cyclosilicate in HFrEF and Hyperkalemia: REALIZE-K Design and Baseline Characteristics.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF). However, MRAs are often underused because of hyperkalemia concerns. OBJECTIVES: The purpose of this study was to assess whether sodium zirconium cyclosilicate (SZC), a nonabsorbed crystal that traps and rapidly lowers potassium, enables MRA use in patients with HFrEF and prevalent hyperkalemia (or at high risk). METHODS: REALIZE-K is a prospective, double-blind, placebo-controlled trial in patients with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction ≤40%), optimal therapy (except MRA), and prevalent hyperkalemia (or at high risk). During the open-label run-in, all participants underwent protocol-mandated spironolactone titration (target: 50 mg daily); those with prevalent (cohort 1) or incident (cohort 2) hyperkalemia during titration started SZC. Participants achieving normokalemia while on spironolactone ≥25 mg daily were randomized to continuing SZC or matching placebo for 6 months. The primary composite endpoint was proportion of participants with optimal response (normokalemia, on spironolactone ≥25 mg daily, no rescue for hyperkalemia [months 1-6]). RESULTS: Of 365 patients (run-in), 202 were randomized. Baseline characteristics included mean age 70 years, prevalent comorbidities (78% estimated glomerular filtration rate <60 mL/min/1.73 m2, 38% atrial fibrillation/flutter), high N-terminal pro B-type natriuretic peptide (median 1,136 pg/mL), and high HFrEF therapy use (64% sacubitril/valsartan, 96% beta-blocker, 42% sodium glucose co-transporter 2 inhibitor). At randomization, 78% were receiving spironolactone 50 mg daily. CONCLUSIONS: REALIZE-K is the first trial to evaluate whether SZC can enable rapid and safe MRA optimization and long-term continuation in patients with HFrEF and prevalent/high risk of hyperkalemia. (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients with Symptomatic HFrEF Receiving Spironolactone; NCT04676646).

Rationale and design of CONTINUITY: a Phase 4 randomized controlled trial of continued post-discharge sodium zirconium cyclosilicate treatment versus standard of care for hyperkalemia in chronic kidney disease.

Background: Individuals with chronic kidney disease (CKD) hospitalized with hyperkalemia are at risk of hyperkalemia recurrence and re-hospitalization. We present the rationale and design of CONTINUITY, a study to examine the efficacy of continuing sodium zirconium cyclosilicate (SZC)-an oral, highly selective potassium (K+) binder-compared with standard of care (SoC) on maintaining normokalemia and reducing re-hospitalization and resource utilization among participants with CKD hospitalized with hyperkalemia. Methods: This Phase 4, randomized, open-label, multicenter study will enroll adults with Stage 3b-5 CKD and/or estimated glomerular filtration rate <45 mL/min/1.73 m2, within 3 months of eligibility screening, hospitalized with a serum potassium (sK+) level of >5.0-≤6.5 mmol/L, without ongoing K+ binder treatment. The study will include an in-hospital phase, where participants receive SZC for 2-21 days, and an outpatient (post-discharge) phase. At discharge, participants with sK+ 3.5-5.0 mmol/L will be randomized (1:1) to SZC or SoC and monitored for 180 days. The primary endpoint is the occurrence of normokalemia at 180 days. Secondary outcomes include incidence and number of hospital admissions or emergency department visits both with hyperkalemia as a contributing factor, and renin-angiotensin-aldosterone system inhibitor down-titration. The safety and tolerability of SZC will be evaluated.Ethics approval has been received from all relevant ethics committees. Enrollment started March 2022 and the estimated study end date is December 2023. Conclusions: This study will assess the potential of SZC versus SoC in managing people with CKD and hyperkalemia post-discharge. Trial registration: ClinicalTrials.gov identifier: NCT05347693; EudraCT: 2021-003527-14, registered on 19 October 2021.

Relationship Between Asthma Control as Measured by the Asthma Impairment and Risk Questionnaire (AIRQ) and Patient Perception of Disease Status, Health-Related Quality of Life, and Treatment Adherence.

Purpose: Critical asthma outcomes highlighted in clinical guidelines include asthma-related quality of life, asthma exacerbations, and asthma control. An easy-to-implement measure of asthma control that assesses both symptom impairment and exacerbation risk and reflects the impact of asthma on patients' lives is lacking. Hence, the objective of this study was to assess the Asthma Impairment and Risk Questionnaire (AIRQ®) construct validity relative to patient self-perception of asthma status and validated disease-specific patient-reported outcome (PRO) measures. Patients and methods: Baseline data were analyzed from patients (aged ≥ 12 years) with asthma participating in a 12-month observational study assessing the ability of AIRQ to predict exacerbations. At entry, patients completed a sociodemographic questionnaire, AIRQ, 3 questions addressing self-perceived asthma status, Saint George's Respiratory Questionnaire (SGRQ), mini-Asthma Quality of Life Questionnaire (AQLQ), and Adult Asthma Adherence Questionnaire (AAAQ). Descriptive statistics were calculated for demographic and clinical characteristics. AIRQ construct validity was evaluated by assessing correlations between total AIRQ score and patient self-assessments, SGRQ, mini-AQLQ, and AAAQ scores. Comparisons of SGRQ, mini-AQLQ, and AAAQ total and component/domain scores by AIRQ control category were performed using general linear models and Scheffe's post hoc adjustments for pairwise comparisons. Results: A total of 1112 patients were enrolled: 70% female, 78% White, mean (standard deviation) age 43.9 (19.5) years. There were highly significant correlations between AIRQ score and patient self-perception of overall control (r = 0.69; p < 0.001), total SGRQ (r = 0.74, p < 0.001), and mini-AQLQ (r = -0.78, p < 0.001) scores. As AIRQ control category worsened, so did total and domain SGRQ, mini-AQLQ, and AAAQ impediment-to-inhaled-corticosteroid-adherence scores (all pairwise comparisons p < 0.001). Conclusion: Findings demonstrate the construct validity of AIRQ relative to patient self-perception of asthma status, disease-specific PRO measures, and treatment adherence barriers. AIRQ can be a useful instrument to raise awareness of the unrecognized impacts of asthma on patients' lives.

Aripiprazole in bipolar depression: a pooled, post-hoc analysis by severity of core depressive symptoms.

OBJECTIVE: This post-hoc analysis of pooled data from two similarly designed trials assessed the impact of aripiprazole monotherapy vs. placebo on treatment outcomes based on baseline severity of core depressive symptoms in patients with bipolar I disorder. METHODS: Patients were classified as severely depressed (Bech-6 Total score > 15) or less severely depressed (Bech-6 Total score < 15). Efficacy was assessed by mean changes in Montgomery-Åsberg Depression Rating Scale (MADRS) Total and MADRS-6 subscale scores from baseline to endpoint using a mixed model repeated measures analysis. RESULTS: A total of 133 patients (n = 62 on active aripiprazole) were classified as severely depressed and 612 patients (n = 309 aripiprazole) as less severely depressed. At endpoint, the mean MADRS Total score reduction for severely depressed patients receiving aripiprazole compared with placebo was -19.4 vs. -15.4 (P = 0.14), whereas MADRS-6 subscale score reduction for patients receiving aripiprazole compared with placebo was -13.8 vs. -10.3 (P = 0.07). Adverse event profiles were similar between the two severity groups. CONCLUSIONS: Symptomatic improvements assessed here suggest that aripiprazole monotherapy at the doses studied may provide some improvements in core symptoms of depression in patients with bipolar I disorder who were more severely depressed.

The prevalence of predialysis hyperkalemia and associated characteristics among hemodialysis patients: The RE-UTILIZE study.

INTRODUCTION: Hyperkalemia (HK), defined as serum potassium (K+ ) >5.0 mEq/L, is an independent predictor of mortality in patients on maintenance hemodialysis (HD). This study investigated the annual prevalence of HK and examined patient characteristics potentially associated with a higher annual HK prevalence. METHODS: This retrospective observational cohort study used Dialysis Outcomes and Practice Patterns Study (DOPPS) survey data from US patients undergoing in-center HD thrice weekly from 2018 to 2019. The primary endpoint was the proportion of patients with any predialysis HK (K+ >5.0 mEq/L) within 1 year from the index date (date of DOPPS enrollment), using the first hyperkalemic K+ value. Secondary endpoints were the proportion of patients with moderate-to-severe (K+ >5.5 mEq/L) or severe (K+ >6.0 mEq/L) HK. FINDINGS: Overall, 9347 patients on HD were included in this analysis (58% male and 49% aged >66 years). Any predialysis HK (K+ >5.0 mEq/L) occurred in 74% of patients within 1 year of the index date, 52% within 3 months, and 38% within 1 month. The annual prevalence of moderate-to-severe and severe HK was 43% and 17%, respectively. Recurrent HK (at least two K+ >5.0 mEq/L within 1 year) occurred in 60% of patients, and 2.8% of patients were prescribed an oral K+ binder. Multivariable logistic regression analysis showed younger age, female sex, Hispanic ethnicity, and renin-angiotensin-aldosterone system inhibitor use were significantly associated with a higher annual prevalence of any predialysis HK, while Black race, obesity, recent initiation of HD, and dialysate K+ bath concentration ≥3 mEq/L were associated with a lower prevalence of HK. DISCUSSION: The annual prevalence of predialysis HK and recurrence were high among US patients on HD, whereas oral K+ binder use was low. Further studies are needed to understand the impact of dialysate K+ bath concentrations on predialysis HK among patients on HD.

The Asthma Impairment and Risk Questionnaire (AIRQ) Control Level Predicts Future Risk of Asthma Exacerbations.

BACKGROUND: The Asthma Impairment and Risk Questionnaire (AIRQ) is a 10-item, equally weighted, yes/no control tool validated in patients with asthma aged 12 years and older. OBJECTIVE: To evaluate AIRQ's ability to predict patient-reported exacerbations over 12 months. METHODS: Patients completed a baseline AIRQ during an in-person enrollment visit and reported exacerbations (ie, asthma-related courses of oral corticosteroids, emergency department/urgent care visits, and hospitalizations) via monthly online surveys. Logistic regressions were performed using AIRQ control level (well-controlled [WC], not well-controlled [NWC], very poorly controlled [VPC]), age, sex, race, and body mass index as covariates and 1 or more and 2 or more exacerbations as the dependent variables (adjusted odds ratios [OR] and 95% Wald CIs). Kaplan-Meier analyses of time to first exacerbation by AIRQ control level were performed. RESULTS: A total of 1,112 patients were enrolled; 1,070 completed 1 or more surveys over 12 months (mean ± SD 10.5 ± 2.8 months); 70.5% female; age 43.9 ± 19.3 years; 20.4% non-White; body mass index 30.6 ± 8.7 kg/m2; AIRQ: WC 35.2%, NWC 38.1%, VPC 26.6%. A total of 45.7% of patients reported 1 or more exacerbations and 26.7% 2 or more exacerbations (WC 28.4% ≥ 1, 11.1% ≥ 2; NWC 46.3% ≥ 1, 27.9% ≥ 2; VPC 67.7% ≥ 1, 45.6% ≥ 2). The ORs for 1 or more exacerbations NWC versus WC were 2.1 (CI 1.6-2.9), and VPC versus WC were 4.6 (CI 3.3-6.5). The ORs for 2 or more exacerbations NWC versus WC were 3.1 (CI 2.1-4.6), and VPC versus WC were 6.1 (CI 4.0-9.1). Kaplan-Meier curves demonstrated clear differentiation of time to first exacerbation by AIRQ control level (P < .001). CONCLUSIONS: The AIRQ control level predicts exacerbation risk over 12 months and probability of time to first exacerbation.

Efficacy and safety of adjunctive aripiprazole in major depressive disorder in older patients: a pooled subpopulation analysis.

OBJECTIVES: To evaluate the efficacy and safety of adjunctive aripiprazole compared with standard antidepressant therapy (ADT) for older patients with major depressive disorder (MDD) who demonstrated an incomplete response to standard antidepressant monotherapy. METHODS: Data from three similar 14-week studies (an 8-week prospective ADT treatment phase and a 6-week randomized, double-blind phase) of aripiprazole augmentation were pooled for this post hoc analysis. Two age groups were defined: younger patients (aged 18-49 years) and older patients (aged 50-67 years). The older patient group was further divided into three subgroups: 50-55, 56-60, and 61-67 years. The efficacy endpoint was the mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from end of the prospective phase (Week 8) to endpoint (Week 14, last observation carried forward (LOCF)). Remission was defined as MADRS total score ≤10 at endpoint. RESULTS: Four hundred and nine older patients (placebo, n = 198; aripiprazole, n = 211) and 679 younger patients (placebo, n = 341; aripiprazole, n = 338) were included in this analysis. Older patients receiving aripiprazole demonstrated significantly greater improvement in MADRS total score versus placebo at Week 14 (-10.0 vs. -6.4; p < 0.001; LOCF), similar to the improvement seen in younger patients. Remission rates were significantly higher with aripiprazole versus placebo in older (32.5% vs. 17.1%; p < 0.001) and younger (26.9% vs. 16.4%; p < 0.001) patients. Akathisia was the most common adverse event in both the older (17.1%) and younger (26.0%) patient groups. CONCLUSIONS: Adjunctive aripiprazole was effective in improving depressive symptoms in older patients, 50-67 years, with MDD who have had an inadequate response to standard antidepressant medication.

Use of a Digital Chronic Obstructive Pulmonary Disease Respiratory Tracker in a Primary Care Setting: A Feasibility Study.

INTRODUCTION: Telemonitoring is a promising self-management strategy to improve health care outcomes. This study evaluated real-world adoption of the chronic obstructive pulmonary disease (COPD) Co-Pilot daily symptom monitoring tool by patients and primary care providers (PCPs). METHODS: An open-label, 6-month, single-arm, multicenter, noninterventional feasibility study enrolled 97 patients aged ≥ 40 years with symptomatic or poorly controlled COPD and ≥ 10 pack-year smoking history. Patients received smartphones and training to use the COPD Co-Pilot application. During the study, patients tracked symptoms daily; an increase in symptom score of ≥ 1.0 point from baseline (symptom alert) prompted patients to contact their PCP via toll-free number. The primary endpoint was time to clinical recommendation (TTCR) from a symptom alert; adherence to completing daily symptom reports through the COPD Co-Pilot application and patient satisfaction were also measured. RESULTS: Overall, 87 of 96 patients (90.6%) received 2142 symptom alerts; 42 alerts (equivalent to 2% of all symptom alerts) resulted in 23 patients contacting their PCP. Median TTCR was 7.1 h (interquartile range [IQR]: 4.0-29.9). Among 15 patients using the toll-free number, median TTCR was 2.1 h (IQR 0.0-7.2) versus 19.6 h (IQR 4.5-45.2) for eight patients using other contact methods. Average COPD Co-Pilot adherence overall was 75.2% (95% CI 74.6-75.9). Patients responded favorably regarding the application's ease of use, functionality, and information provided. CONCLUSIONS: The COPD Co-Pilot tool was associated with relatively high levels of adherence, suggesting patients' willingness to monitor symptoms daily. Although a limited number of patients initiated PCP contact, patients who used the study-provided toll-free number had substantially shorter median TTCR, suggesting that this tool could help empower patients to better manage their COPD.

The Impact of Budesonide/Formoterol pMDI Medication Reminders on Adherence in Chronic Obstructive Pulmonary Disease (COPD) Patients: Results of a Randomized, Phase 4, Clinical Study.

PURPOSE: Among patients with chronic obstructive pulmonary disease (COPD), adherence to inhaled medication leads to fewer exacerbations and improved health status. The goal of the present study was to evaluate the effects of medication reminders via the BreatheMate device on adherence in patients with COPD. PATIENTS AND METHODS: A 6-month, phase 4, randomized, multicenter, open-label US study (NCT02864342) enrolled 138 patients aged ≥40 years with moderate to very severe COPD and ≥10 pack-year smoking history. Patients in the intervention (n = 68) and control (n = 70) groups received the BreatheMate device, smartphone application, and vouchers to redeem pressurized metered-dose inhalers (pMDIs) for the prescribed 2 puffs of budesonide/formoterol 160/4.5 µg twice daily. The intervention group also received twice-daily electronic reminders to take budesonide/formoterol. The primary endpoint was the mean number of sets of adherent puffs/day (4 puffs: 2 puffs within 60 minutes, twice daily) over 6 months. Secondary endpoints included adherence by three 60-day intervals, usage days, prescription refills, and Clinical COPD Questionnaire (CCQ) score. Study enrollment terminated early due to issues with inconsistent syncing. RESULTS: A higher mean proportion of adherent days (77.6% vs 60.2%; P <0.001) and sets of adherent puffs/day (1.61 vs 1.33; P <0.001) were recorded for the intervention group versus the control group. Intervention group adherence was higher than that of the control group for each 60-day interval (P <0.001); the intervention group was 3.07 (95% confidence interval: 1.49-6.52) times more likely than the control group to be adherent for ≥80% of study days. Overuse (>2 sets of 2 puffs/day), underuse (<2 sets of 2 puffs/day), and no use days were lower in the intervention group versus control (P <0.05). Patients aged ≥65 years had higher adherence (P <0.001). CONCLUSION: Medication reminders through the BreatheMate device and application produced greater adherence to inhaled therapy in patients with COPD.

Dual-combination maintenance inhaler preferences in asthma and chronic obstructive pulmonary disease: A patient-centered benefit-risk assessment.

BACKGROUND: A variety of dual-combination maintenance inhalers are used to treat asthma and chronic obstructive pulmonary disease (COPD). Understanding patient preferences for treatment attributes may help select an optimal treatment from the patient perspective. METHODS: Patient preferences for maintenance inhaler device and medication attributes were elicited through a discrete choice experiment and used in benefit-risk assessments to calculate predicted choice probabilities (PrCPs) for 14 dual-combination maintenance inhalers in four treatment classes: lower- and higher-dose inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) inhalers for asthma, and ICS/LABA and long-acting muscarinic antagonist (LAMA)/LABA inhalers for COPD. RESULTS: For all treatment classes, reduced exacerbations and faster onset of action were the most important attributes. For all classes, patients were willing to tolerate an extra yearly exacerbation to decrease the medication's onset of action from 30 to 5 min. For patients with asthma using lower-dose ICS/LABA (n = 497), budesonide/formoterol fumarate dihydrate (80 µg/4.5 µg) pressurized metered-dose inhaler (pMDI) had the highest PrCP (28.4%), and for those using a higher-dose ICS/LABA (n = 285), PrCPs were highest for mometasone furoate/formoterol fumarate dihydrate (200 µg/5 µg) pMDI (27.0%) and budesonide/formoterol fumarate dihydrate (160 µg/4.5 µg) pMDI (26.9%). For patients with COPD using an ICS/LABA (n = 574), budesonide/formoterol fumarate dihydrate (160 µg/4.5 µg) pMDI had the highest PrCP (56.6%), and for those using a LAMA/LABA inhaler (n = 217), tiotropium/olodaterol (2.5 µg/2.5 µg) soft mist inhaler had the highest PrCP (42.3%). CONCLUSIONS: Patient preference data for maintenance inhaler attributes can be used to identify a preference order of inhalers in different treatment classes.

A pooled MADRS/IDS cross-correlation analysis: clinician and patient self-report assessment of improvement in core depressive symptoms with adjunctive aripiprazole.

BACKGROUND: These analyses aimed to examine the pattern of improvement in depression symptoms with adjunctive aripiprazole. METHODS: Data were pooled (724 subjects: n = 356 placebo, n = 368 aripiprazole) from 2 double-blind, 6-week aripiprazole studies. Pearson correlation coefficients (r) were calculated between changes on the Montgomery-Asberg Depression Rating Scale (MADRS) line items and selected Inventory of Depressive Symptomatology (IDS) line items using last observation carried forward. The magnitude of change was expressed as a between-group effect size (ES). RESULTS: At end point, adjunctive aripiprazole demonstrated significant improvement versus antidepressant therapy alone in 8 of the 10 MADRS items (MADRS total score Cohen effect size = 0.37) and 12 of the 30 IDS items (IDS total score Cohen ES = 0.18). Analysis of correlation data identified 5 MADRS items assessing mood, lassitude, inability to feel, self-worth, and suicidal thoughts that correlated with similar IDS items; these showed a similar pattern of rapid, sustained response to adjunctive aripiprazole and a similar ES. Other symptoms associated with depression (tension associated with feeling anxious, irritability, and lack of concentration) did not show statistically significant changes on either scale at end point. The IDS identified an additional 3 important depression-related symptoms (diminished libido, view of self, and interpersonal sensitivity) that showed significant rapid and sustained improvement with adjunctive aripiprazole. CONCLUSIONS: This cross-correlation analysis confirmed that improvement in core depressive symptoms with adjunctive aripiprazole was identified by both clinicians and patients. Clinically, these changes were maintained during the study. Theoretically, these findings lead to important questions regarding neurochemical changes produced by aripiprazole when used in combination with antidepressants.