The magnitude and sustainability of treatment benefit of zuranolone on function and well-being as assessed by the SF-36 in adult patients with MDD and PPD: An integrated analysis of 4 randomized clinical trials.

BACKGROUND: Major depressive disorder (MDD) and postpartum depression (PPD) are disabling conditions. This integrated analysis of MDD and PPD clinical trials investigated the impact of zuranolone-a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and neuroactive steroid under investigation for adults with MDD and approved as an oral, once-daily, 14-day treatment course for adults with PPD in the US-on health-related quality of life, including functioning and well-being, as assessed using the 36-item Short Form Health Survey V2 (SF-36). METHODS: Integrated data from 3 MDD (201B, MOUNTAIN, WATERFALL) and 1 PPD trial (ROBIN) for individual SF-36 domains were compared for zuranolone (30- and 50-mg) vs placebo at Day (D)15 and D42. Comparisons between zuranolone responders (≥50 % reduction from baseline in 17-item Hamilton Depression Rating Scale total score) and nonresponders were assessed. RESULTS: Overall, 1003 patients were included (zuranolone, n = 504; placebo, n = 499). Significant differences in change from baseline (CFB) to D15 for patients in zuranolone vs placebo groups were observed in 6/8 domains; changes were sustained or improved at D42, with significant CFB differences for all 8 domains. Zuranolone responders had significantly higher CFB scores vs nonresponders for all domains at D15 and D42 (p < 0.001). LIMITATIONS: Two zuranolone doses were integrated across populations of 2 disease states with potential differences in functioning, comorbidities, and patient demographics. All p-values presented are nominal. CONCLUSIONS: Integrated data across 4 zuranolone clinical trials showed improvements in functioning and well-being across all SF-36 domains. Benefits persisted after completion of treatment course at D42.

Real-world reporting rates of administration-site reactions with on-demand treatment of hereditary angioedema attacks.

Background: Hereditary angioedema (HAE) is characterized by recurrent and unpredictable episodes of subcutaneous and/or submucosal swelling. Objective: To characterize the real-world treatment burden associated with existing on-demand therapies, we analyzed administration-site adverse drug reactions (ADR) associated with approved on-demand HAE therapies reported in the U.S. Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS). Methods: We searched the FAERS database from October 1, 2009, to March 31, 2022, for reports of all FDA-approved on-demand therapies for HAE: plasma-derived C1-inhibitor (pdC1-INH), ecallantide, icatibant, and recombinant C1-inhibitor (rhC1-INH). ADRs in which the drug was listed as the "primary suspect" were recorded for each drug. ADR preferred terms were grouped into 18 ADR domains based on semantic and/or clinical similarity, and the number of reports for each drug was calculated per year from the time of approval through March 2022, and descriptive results were presented. Preferred terms associated with administration-site ADRs identified from clinical trials and denoted on approved HAE drug U.S. package inserts were examined in a complementary analysis. Results: The highest reported rates of administration-site ADRs per year were site pain (17.9 reports per year), site erythema (7.4 per year), and site swelling (6.7 per year). RhC1-INH was the only drug for which access-site complications and/or malfunctions were reported (9.5 per year). PdC1-INH had the highest rate of incorrect route of product administration (3.7 per year). PdC1-INH showed statistically significant elevated reporting rate of injection-site reactions (reporting odds ratio [ROR] 3.59 [2.36-5.46]; empirical Bayesian geometric mean [EBGM] 1.97 [1.39]). Icatibant and rhC1-INH showed a statistical trend toward an increased reporting rate of administration-site reactions. Conclusion: Real-world data from FAERS were generally consistent with adverse events reported in clinical trials and suggest that patients experience substantial treatment burden associated with FDA-approved parenteral on-demand therapies for HAE attacks. It should be noted that ADR rates are not exposure adjusted and are based on spontaneous reporting.

Capacity-Building for Collecting Patient-Reported Outcomes and Experiences (PRO) Data Across Hospitals.

PURPOSE: Patient-reported outcomes and experiences (PRO) data are an integral component of health care quality measurement and PROs are now being collected by many healthcare systems. However, hospital organizational capacity-building for the collection and sharing of PROs is a complex process. We sought to identify the factors that facilitated capacity-building for PRO data collection in a nascent quality improvement learning collaborative of 16 hospitals that has the goal of improving the childbirth experience. DESCRIPTION: We used standard qualitative case study methodologies based on a conceptual framework that hypothesizes that adequate organizational incentives and capacities allow successful achievement of project milestones in a collaborative setting. The 4 project milestones considered in this study were: (1) Agreements; (2) System Design; (3) System Development and Operations; and (4) Implementation. To evaluate the success of reaching each milestone, critical incidents were logged and tracked to determine the capacities and incentives needed to resolve them. ASSESSMENT: The pace of the implementation of PRO data collection through the 4 milestones was uneven across hospitals and largely dependent on limited hospital capacities in the following 8 dimensions: (1) Incentives; (2) Leadership; (3) Policies; (4) Operating systems; (5) Information technology; (6) Legal aspects; (7) Cross-hospital collaboration; and (8) Patient engagement. From this case study, a trajectory for capacity-building in each dimension is discussed. CONCLUSION: The implementation of PRO data collection in a quality improvement learning collaborative was dependent on multiple organizational capacities for the achievement of project milestones.

Factors Associated With Response to Growth Hormone in Pediatric Growth Disorders: Results of a 5-year Registry Analysis.

Context: Growth hormone (GH) therapy can increase linear growth in patients with growth hormone deficiency (GHD), Turner syndrome (TS), Noonan syndrome (NS), and Prader-Willi syndrome (PWS), although outcomes vary by disease state. Objective: To assess growth and identify factors associated with growth response with long-term GH therapy. Methods: Data from pediatric patients with GHD, TS, NS, and PWS obtained at GH treatment initiation (baseline) and annually for 5 years in the ANSWER Program and NordiNet® IOS were analyzed retrospectively. Height standard deviation score (HSDS) was assessed over time, and multivariate analyses determined variables with significant positive effects on growth outcomes in each patient cohort. Results: Data from patients with GHD (n = 12 683), TS (n = 1307), NS (n = 203), and PWS (n = 102) were analyzed. HSDS increased over time during GH treatment in all cohorts. Factors with significant positive effects on ΔHSDS were younger age at GH initiation and lower HSDS at baseline (all cohorts) and higher GH dose (GHD and TS only); sex had no effect in any cohort. The modeling analysis showed that ΔHSDS was greatest in year 1 and attenuated over consecutive years through year 5. Estimated least-squares mean ΔHSDS values at year 5 by cohort were 1.702 (females) and 1.586 (males) in GHD, 1.033 in TS, 1.153 in NS, and 1.392 in PWS. Conclusion: Long-term GH therapy results in large increases in HSDS in patients with GHD, TS, NS, and PWS. Greater gains in HSDS can be obtained with higher GH doses and earlier initiation of treatment.

Effect of Zuranolone on Concurrent Anxiety and Insomnia Symptoms in Women With Postpartum Depression.

Objective: Concurrent anxiety and/or insomnia symptoms in women with postpartum depression (PPD) are common and associated with more severe PPD. The effects of zuranolone on concurrent anxiety and/or insomnia symptoms and on patient-perceived functional health in women with PPD in the ROBIN study are reported.Methods: The phase 3, double-blind, randomized, placebo-controlled trial (conducted January 2017-December 2018) included women aged 18-45 years, ≤ 6 months postpartum, with PPD (onset of DSM-5-defined major depressive episode in the third trimester or ≤ 4 weeks postpartum) and baseline 17-item Hamilton Depression Rating Scale (HDRS-17) total score ≥ 26. Women were randomized 1:1 to once-daily oral zuranolone 30 mg (n = 77) or placebo (n = 76) for 14 days with follow-up through day 45. Concurrent remission of depressive and anxiety symptoms (Hamilton Anxiety Rating Scale total score ≤ 7 plus HDRS-17 total score ≤ 7 or Montgomery-Asberg Depression Rating Scale total score ≤ 10), improvement in insomnia symptoms, patient-perceived functional health, and treatment effect sizes described by number needed to treat (NNT) were assessed. Analyses were exploratory; P values are nominal.Results: Rates of concurrent remission of depressive and anxiety symptoms were higher with zuranolone versus placebo (P < .05) at days 3, 15, and 45; the rate of sustained concurrent remission (ie, at both days 15 and 45) was also higher with zuranolone (P < .05). Anxiety symptoms (assessed by HDRS-17 anxiety/somatization subscale and Edinburgh Postnatal Depression Scale anxiety subscale) improved with zuranolone versus placebo (P < .05) at days 3 through 45. Potential benefits on insomnia symptoms and patient-perceived functional health were observed. Day 15 NNTs were 5 for both HDRS-17 response and remission.Conclusions: Zuranolone was associated with concurrent improvements in depressive and anxiety symptoms, with beneficial effects on insomnia symptoms and patient-perceived functional health in adults with PPD.Trial Registration: ClinicalTrials.gov identifier: NCT02978326.

Using Potentially Preventable Severe Maternal Morbidity to Monitor Hospital Performance.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) measure of severe maternal morbidity (SMM) quantifies the burden of SMM but is not restricted to potentially preventable SMM. The authors adapted the CDC SMM measure for this purpose and evaluated it for use as a hospital performance measure. METHODS: Guidelines for defining performance SMM (pSMM) were (1) exclusion of preexisting conditions from outcome; (2) exclusion of inconsistently documented outcomes; and (3) risk adjustment for conditions that preceded hospitalization. California maternal hospital discharge data from 2016 to 2017 were used for model development, and 2018 data were used for model testing and evaluation of hospital performance. Separate models were developed for hospital types (Community, Teaching, Integrated Delivery System [IDS], and IDS Teaching), generating model-based expected pSMM values. Observed-to-expected (O/E) ratios were calculated for hospitals and used to categorize them as overperforming, average performing, or underperforming using 95% confidence intervals. Performance categories were compared for pSMM vs. CDC SMM (excluding blood transfusion). RESULTS: The overall 2016-2018 pSMM rate was 0.44%. All hospital types had over- and underperformers, and the proportions of Community, Teaching, IDS, and IDS Teaching hospitals whose performance differed from their performance on the CDC SMM measure were 12.1%, 25.0%, 38.9%, and 66.7%, respectively. CONCLUSION: The rate of potentially preventable SMM as defined by pSMM (0.44%) was less than half the previously published rate of CDC SMM (1.03%). pSMM identified differences in performance across hospitals, and pSMM and CDC SMM classified hospitals' performances differently. pSMM may be suitable for hospital comparisons because it identifies potentially preventable, hospital-acquired SMM that should be responsive to quality improvement activities.

The Association of Alopecia Areata-Related Emotional Symptoms with Work Productivity and Daily Activity Among Patients with Alopecia Areata.

INTRODUCTION: Patients with alopecia areata (AA) experience psychological and psychosocial symptoms including depression, anxiety, anger, social withdrawal, embarrassment, and low self-esteem. While multiple studies have measured the detrimental emotional impact of AA on patient quality of life, evidence of its effect on work productivity loss (WPL) and daily activities is limited. This study aimed to assess the extent of AA-related emotional symptom (ES) burden on work productivity and activity impairment. METHODS: A cross-sectional survey of dermatologists and their adult patients with AA was conducted in the USA in 2019. Dermatologists provided assessments of patients' clinical characteristics, while patients completed sociodemographic questionnaires along with two validated patient-reported outcome measures of the Work Productivity and Activity Impairment (WPAI) and the AA Patient Priority Outcomes (AAPPO) ES subscale. The WPAI assessed AA-related WPL (employed respondents) and activity impairment (all respondents), and the AAPPO-ES assessed AA-related frequency of feeling self-conscious, embarrassed, sad, or frustrated. Multiple linear regression models were fitted to both WPAI scores with the AAPPO ES as an independent variable. RESULTS: A total of 242 patients with a mean (SD) age of 39.2 (13.3) years, treated by 59 dermatologists, were evaluated. Mean (SD) ES score was 2.0 (1.1). Mean (SD) work productivity loss [n = 170] and activity impairment [n = 242] were 12.2% (17.4%) and 13.3% (18.3%), respectively. After adjusting for covariates, WPL increased by 4.1% [95% confidence interval (CI) 1.6-6.7%; p = 0.002] and activity impairment increased by 3.1% (95% CI 0.7-5.4%; p = 0.010) for every 1-point increase in ES. For an average patient, a 1-SD decrease (about 1 point) on the ES scale substantially reduced WPL and activity impairment (by at least 25%). CONCLUSIONS: Patients with AA reported significant increases in WPL and activity impairment associated with worsening AA-related ES. These findings underscore the substantial emotional and psychosocial burden among patients with AA and a need for improved treatment options.

Treatment Patterns and Treatment Satisfaction Among Adults with Alopecia Areata in the United States.

INTRODUCTION: Alopecia areata (AA), an autoimmune disease, is characterized by non-scarring hair loss involving the scalp, face, and/or body. Prior to 2022, no US Food and Drug Administration (FDA)-approved treatments for AA were available in the USA; existing treatment options had limited efficacy and durability and are often associated with side effects. This study aimed to evaluate the current AA treatment patterns and treatment satisfaction as reported by dermatologists. METHODS: Real-world data from a 2019 cross-sectional survey of US dermatologists and their adult patients with AA were analyzed. Dermatologists provided comprehensive data on their patients with AA, including AA dermatologist-assessed severity, treatments, treatment duration, treatment satisfaction, and reasons for dissatisfaction. The switching patterns among the proportion of patients on each of the treatment groups at the time of survey and, for those with prescription history, were reported. RESULTS: A total of 442 patients with AA, treated by 90 dermatologists, were included in this analysis. At the time of survey, 45% of patients were being prescribed a combination of corticosteroids, 21% injectable corticosteroids, 11% topical corticosteroids/topical calcineurin inhibitor, and 10% immunomodulator as monotherapy or in combination. The majority (65%) of patients had no prior reported therapy. Among patients who were reported to have a prior therapy, frequent switching was to combination corticosteroids, injectable corticosteroids, and immunomodulators. Overall treatment dissatisfaction was high (24% dissatisfied and 29% neutral) and increased with AA severity. CONCLUSIONS: This analysis provides a snapshot of the different local and systemic treatment options currently being used in a real-world treatment setting. Unfortunately, none of these treatments provide a sustainable, safe, and relapse-free solution, which leads to high treatment dissatisfaction rates and hence indicates a significant unmet need for the new and advanced treatment options for patients with AA.

Severe Maternal Morbidity in California Hospitals: Performance Based on a Validated Multivariable Prediction Model.

BACKGROUND: Severe maternal morbidity (SMM) is under development as a quality indicator for maternal health care. The aim of this study is to evaluate California hospital performance based on a standardized SMM measure. METHODS: California maternal hospital delivery discharge data from 2016 to 2017 were used to develop logistic regression models for SMM, adjusted for clinical risk factors at admission. Data from 2018 were used to test the models and evaluate hospital performance. SMM was defined per the Centers for Disease Control and Prevention, including (excluding) blood transfusion. Independent models were developed for each hospital type: community, teaching, integrated delivery system (IDS), and IDS teaching. Within each type, model-based expected SMM values and observed-to-expected (O/E) ratios were calculated for each hospital. For each hospital type, hospitals were ranked by O/E ratio, and over- and underperforming hospitals were identified using 95% confidence intervals. RESULTS: Rates of SMM including (excluding) transfusion by hospital type were 1.7% (0.9%) for community, 2.7% (1.5%) for teaching, 2.3% (1.2%) for IDS, and 3.0% (1.6%) for IDS teaching hospitals. In higher-volume community hospitals (≥ 500 births/year), the proportion of underperformers including (excluding) transfusion was 20.7% (11.0%). Summing over all hospital types, 25.3% (14.9%) of hospitals were identified as underperformers in that they experienced significantly more SMM events than expected including (excluding) transfusion. CONCLUSION: California hospital discharge data demonstrated significant hospital variation in standardized childbirth SMM. These data suggest that a standardized SMM measure may help guide and monitor statewide quality improvement efforts.

Reporting of Thromboembolic Events with JAK Inhibitors: Analysis of the FAERS Database 2010-2019.

INTRODUCTION: A potentially elevated risk for pulmonary thrombosis with Janus kinase inhibitors (JAKinibs) was identified, as well as an increased risk for portal vein thrombosis, in ruxolitinib patients. Consequently, the objective of this investigation was to repeat a comprehensive analysis of the US FDA's Adverse Event Reporting System (FAERS) database to assess postmarketing reporting rates of thromboembolic events (TEs) in patients treated with JAKinibs. METHODS: FAERS data (1 January 2010 to 30 September 2019) were searched for reports of all FDA-approved JAKinibs across all indications. For each drug-adverse drug reaction (ADR) pair, the reporting odds ratio (ROR) [two-sided 95% confidence interval (CI)] and empirical Bayesian geometric mean (EBGM) [one-sided 95% lower bound] were calculated to detect drug-ADR pairs with higher-than-expected reporting rates within the FAERS. Significance was declared when both lower 95% CI bounds were > 1. RESULTS: Significantly elevated reporting rates of pulmonary thrombosis were evident with tofacitinib (ROR 2.36 [1.69-3.31]; EBGM 2.01 [1.53]), as was pulmonary embolism with baricitinib (ROR 12.23 [8.35-17.89]; EBGM 7.72 [3.82]) and portal vein thrombosis with ruxolitinib (ROR 4.16 [2.70-6.40]; EBGM 4.52 [3.11]). Deep vein thrombosis reports were increased with baricitinib (ROR 14.84 [9.64-22.84]; EBGM 9.49 [5.91]), as was thrombosis with ruxolitinib (ROR 1.40 [1.20-1.63]; EBGM 1.72 [1.52]). The relationship between the time of treatment initiation and event occurrence indicated that time to events occurred randomly. CONCLUSIONS: This study found significant reporting rates for TEs in patients treated with JAKinibs across brands and indications, providing additional evidence that JAKinibs may be contraindicated in patients at risk of TEs.

Achieving clinical response in postpartum depression leads to improvement in health-related quality of life.

OBJECTIVE: To evaluate the health-related quality of life (HRQoL) burden associated with postpartum depression (PPD), determine the extent to which clinical response impacts HRQoL, and estimate the impact of PPD and clinical response on healthcare resource utilization (HRU) and productivity. METHODS: Patient data (n = 127) from two multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trials evaluating the safety and efficacy of brexanolone injection in adults with PPD were employed for these posthoc analyses. HRQoL and health utility was assessed with the SF-36-v2 Health Survey (SF-36v2) acute version. The 17-item Hamilton Rating Scale for Depression (HAMD-17) total score was used to identify clinical response (≥50% reduction in HAMD-17 total score). Baseline HRQoL burden was assessed by comparison to age- and gender-adjusted population normative data from the 2009 QualityMetric PRO Norming study. The impact of clinical response was evaluated by comparing day 7 and day 30 SF-36v2 scores between clinical responders and non-responders. Interpretations of the meaningfulness of clinical response were indirectly estimated via 2017 National Health and Wellness Survey data linking SF-36v2 mental component summary (MCS) scores to (HRU) and productivity. RESULTS: Baseline HRQoL of patients with PPD was significantly below normative values. Day 7 and day 30 clinical response were associated with large and statistically significant improvements in HRQoL, greater likelihood of meeting SF-36v2 responder definitions, and reduced impairment. MCS levels corresponding to those observed in clinical responders were linked to lower HRU and productivity loss relative to non-responders. CONCLUSIONS: PPD places a substantial burden on HRQoL. Achievement of rapid clinical response (at day 7) and clinical response sustained several weeks following the end of treatment (day 30) led to significant improvement in HRQoL, suggesting the importance of identifying women with PPD and providing effective treatment options.

A scoping review of severe maternal morbidity: describing risk factors and methodological approaches to inform population-based surveillance.

BACKGROUND: Current interest in using severe maternal morbidity (SMM) as a quality indicator for maternal healthcare will require the development of a standardized method for estimating hospital or regional SMM rates that includes adjustment and/or stratification for risk factors. OBJECTIVE: To perform a scoping review to identify methodological considerations and potential covariates for risk adjustment for delivery-associated SMM. SEARCH METHODS: Following the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews, systematic searches were conducted with the entire PubMed and EMBASE electronic databases to identify publications using the key term "severe maternal morbidity." SELECTION CRITERIA: Included studies required population-based cohort data and testing or adjustment of risk factors for SMM occurring during the delivery admission. Descriptive studies and those using surveillance-based data collection methods were excluded. DATA COLLECTION AND ANALYSIS: Information was extracted into a pre-defined database. Study design and eligibility, overall quality and results, SMM definitions, and patient-, hospital-, and community-level risk factors and their definitions were assessed. MAIN RESULTS: Eligibility criteria were met by 81 studies. Methodological approaches were heterogeneous and study results could not be combined quantitatively because of wide variability in data sources, study designs, eligibility criteria, definitions of SMM, and risk-factor selection and definitions. Of the 180 potential risk factors identified, 41 were categorized as pre-existing conditions (e.g., chronic hypertension), 22 as obstetrical conditions (e.g., multiple gestation), 22 as intrapartum conditions (e.g., delivery route), 15 as non-clinical variables (e.g., insurance type), 58 as hospital-level variables (e.g., delivery volume), and 22 as community-level variables (e.g., neighborhood poverty). CONCLUSIONS: The development of a risk adjustment strategy that will allow for SMM comparisons across hospitals or regions will require harmonization regarding: a) the standardization of the SMM definition; b) the data sources and population used; and c) the selection and definition of risk factors of interest.

Brexanolone in Postpartum Depression: Post Hoc Analyses to Help Inform Clinical Decision-Making.

Background: Brexanolone (BRX) injection was approved by the United States Food and Drug Administration in 2019 for the treatment of adults with postpartum depression (PPD) based on two Phase 3 clinical trials. Materials and Methods: Data from the three trials were combined. PPD-specific 17-item Hamilton Rating Scale for Depression (HAMD-17) group-level minimal important difference (MID) and patient-level meaningful change (meaningful change threshold [MCT]) were estimated and applied to differences in BRX versus placebo (PBO) at hour 60 (primary endpoint) and day 30 (end of trial follow-up). Likelihood of HAMD-17 response and remission and Clinical Global Impression of Improvement (CGI-I) response for BRX versus PBO were assessed at hour 60 and as sustained through day 30 using relative risk. Associated number needed to treat (NNT) and number needed to harm (NNH) values were also estimated. Results: Two-hundred nine patients were included. The average HAMD-17 MID estimate was -2.1; the least-squared mean difference between BRX and PBO exceeded this at hour 60 and day 30. Minimal, moderate, and large MCTs were estimated to be -9, -15, and -20 points, respectively. Significantly more BRX-treated than PBO-treated patients achieved minimal, moderate, and large change (all ps < 0.05) at hour 60 and large meaningful response at day 30 (p < 0.05). BRX-treated patients were more likely to sustain HAMD-17 remission and CGI-I response through day 30 versus PBO. NNTs ranged from 4 to 8, with NNH of 97. Conclusions: BRX provided meaningful changes relative to PBO, rapid (hour 60), and sustained improvements (day 30) in PPD symptoms, low NNT, and large NNH. These results may help inform treatment decision-making. Clinicaltrials.gov registration numbers: NCT02614547, NCT02942004, and NCT02942017.

Impact of Weight Change in Adults with Type 2 Diabetes Mellitus: A Literature Review and Critical Analysis.

OBJECTIVE: Weight reduction is a key component of diabetes management in adults with type 2 diabetes mellitus (T2DM), yet the benefits of weight loss in T2DM patients have been difficult to quantify. We examined the medical literature regarding the relationships between weight change and 1) glycemic control and 2) cost and resource use. METHODS: Systematic searches were conducted in the electronic databases Embase, MEDLINE, and the Cochrane Database of Systematic Reviews to identify publications regarding the impact of weight change on T2DM outcomes from 2007 onward. Identified publications were screened for relevance against predefined eligibility criteria, and methodological approaches and results were extracted. Evidence for the impact of weight change on outcomes was evaluated and used to identify strengths, limitations, and gaps in the current literature. RESULTS: The number of studies meeting eligibility criteria for each outcome was: glycemic control (n=38) and cost and resource use (n=11). The relationship between weight change and glycemic control was dependent on the interplay of multiple factors, eg, the weight loss interventions employed, the antidiabetic medication classes used, the time horizon, and baseline BMI and glycemic control. With respect to cost and resource use, the review indicated that savings were associated with weight loss, and increased costs were associated with weight gain. CONCLUSION: Studies regarding weight change in T2DM patients demonstrated varying effects on glycemic control and a positive association with costs and resource use, where weight loss was associated with decreased costs and resource use. Future studies may be able to clarify these relationships.

Associations between commonly used patient-reported outcome tools in postpartum depression clinical practice and the Hamilton Rating Scale for Depression.

The objective of this study is to explore the associations between the patient-reported Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire (PHQ)-9 and clinician-reported 17-item Hamilton Depression Rating Scale (HAMD-17) in order to facilitate clinical decision-making. An integrated efficacy dataset of three randomized placebo-controlled trials (NCT02614547, NCT02942004, and NCT02942017) evaluating brexanolone injection, a neuroactive steroid chemically identical to allopregnanolone, in women with postpartum depression was used for this post hoc analysis. Data were pooled across treatment arms. Associations were assessed at day 30 (end-of-trial follow-up). Pearson correlation assessed the relationship between EPDS and PHQ-9 item and total scores and HAMD-17 total score. Cohen's kappa assessed agreement of EPDS remission (score < 10) and PHQ-9 remission (score < 5) with HAMD-17 remission (score ≤ 7). Ordinary least squares (OLS) regression models were used to develop equations estimating HAMD-17 total scores from EPDS and PHQ-9 scores, respectively. The total scores showed large correlations (HAMD-17/EPDS: r = 0.71, p < 0.001; HAMD-17/PHQ-9: r = 0.75, p < 0.001). Individual EPDS and PHQ-9 items significantly correlated (r= 0.35 to 0.67, all p < 0.001) with HAMD-17 total score. EPDS had 79% sensitivity and 67% specificity to detect HAMD-17 remission; corresponding estimates for PHQ-9 were 76% and 78%. OLS models yielded the following equations: HAMD-17 total = 2.66 + (EPDS total × 0.87) and HAMD-17 total = 3.99 + (PHQ-9 total × 0.97). There were large and statistically significant associations between patient-reported outcomes (EPDS, PHQ-9) and clinician-reported outcomes (HAMD-17) as clinical improvements were associated with patient-reported symptom improvement. These results provide tools to help translate clinical trial data to clinical practice, thus aiding shared decision-making for this critical population.

Hereditary angioedema C1-esterase inhibitor replacement therapy and coexisting autoimmune disorders: findings from a claims database.

In this letter to the editor, we present results of claims data analysis. This claims data analysis supports a hypothesis that in patients with hereditary angioedema due to C1-esterase inhibitor (C1-INH) deficiency, the occurrence and/or symptomatology of coexisting autoimmune disease may be positively influenced by a replacement therapy with plasma derived C1-INH.

Comparison of Quality of Life, Productivity, Functioning and Self-Esteem in Adults Diagnosed With ADHD and With Symptomatic ADHD.

Objective: Investigate the association between diagnosis and outcomes in adults with symptoms of ADHD. Method: The Validate Attitudes and Lifestyle Issues in Depression, ADHD and Troubles with Eating (VALIDATE) study collected sociodemographic and clinical characteristics data, and responses from validated questionnaires on health-related quality of life (HRQoL), work productivity, functioning, and self-esteem. ADHD-diagnosed respondents (n = 444) were matched with respondents with symptomatic ADHD (n = 1,055) within the same sex-by-age group using propensity score matching. Effects of ADHD diagnosis on each outcome were adjusted for covariates that remained imbalanced after matching, using generalized mixed models. Results: After matching, symptomatic respondents (n = 867) had worse outcomes than ADHD-diagnosed respondents (n = 436), as measured by the Work Productivity and Activity Impairment: General Health questionnaire and Sheehan Disability Scale (p < .001). ADHD-diagnosed respondents had better mean EuroQol five-dimensional five-level (EQ-5D-5L) scores and Rosenberg Self-Esteem Scale scores than symptomatic respondents (p < .001). Conclusion: ADHD-diagnosed individuals are more likely to experience better functional performance, work-related productivity, HRQoL, and self-esteem than individuals with symptomatic ADHD.

Caregiver Burden Due to Pulmonary Exacerbations in Patients with Cystic Fibrosis.

OBJECTIVE: To describe the poorly understood burden of pulmonary exacerbations experienced by primary caregivers of children (aged 2-17 years) with cystic fibrosis (CF), who frequently require prolonged hospitalizations for treatment of pulmonary exacerbations with intravenous (IV) antibiotics. STUDY DESIGN: In this prospective observational study, 88 caregivers in Germany, Ireland, the United Kingdom, and the US completed a survey during pulmonary exacerbation-related hospitalizations (T1) and after return to a "well state" of health (T2). The impact of pulmonary exacerbations on caregiver-reported productivity, mental/physical health, and social/family/emotional functioning was quantified. RESULTS: Primary caregivers of children with CF reported significantly increased burden during pulmonary exacerbations, as measured by the 12-item Short-Form Health Survey mental health component and the Work Productivity and Activity Impairment: Specific Health Problem absenteeism, presenteeism, work productivity loss, and activity impairment component scores. Compared to the "well state," during pulmonary exacerbations-related hospitalization caregivers reported lower physical health scores on the Child Health Questionnaire-Parent Form 28. Quality-of-life scores on the Caregiver Quality of Life Cystic Fibrosis scale and total support score on the Multidimensional Scale of Perceived Social Support did not differ significantly between T1 and T2. More caregivers reported a negative impact on family/social/emotional functioning during pulmonary exacerbations than during the "well state." CONCLUSIONS: Pulmonary exacerbations necessitating hospitalization impose a significant burden on primary caregivers of children with CF. Preventing pulmonary exacerbations may substantially reduce this burden.

Patient-reported outcomes in patients with cystic fibrosis with a G551D mutation on ivacaftor treatment: results from a cross-sectional study.

BACKGROUND: Clinical studies demonstrate that ivacaftor (IVA) improves health-related quality of life (HRQoL) in patients aged ≥6 years with cystic fibrosis (CF). The real-world impact of IVA and standard of care (SOC) in groups of patients with G551D and F508del mutations, respectively, was assessed using a survey comprising disease-specific and generic HRQoL measures. METHODS: Patients with CF aged ≥12 years, or aged 6-11 years with caregiver support, with either (1) a G551D mutation and receiving IVA (G551D/IVA) for ≥3 months, or (2) homozygous for F508del and receiving SOC before lumacaftor/IVA availability (F508del/SOC), were eligible to participate in a cross-sectional survey. Demographic and clinical characteristics, and HRQoL measures were compared between patient groups, and multiple regression analyses were conducted. RESULTS: After differences in patient demographic and clinical characteristics were controlled for, significantly better scores were observed in the G551D/IVA group than in the F508del/SOC group on multiple domains of the validated Cystic Fibrosis Questionnaire-Revised and the EuroQol 5-dimensions 5-level questionnaire. CONCLUSIONS: G551D/IVA patients reported better HRQoL than F508del/SOC patients on generic and disease-specific measures in a real-world setting.

Injectable Antihyperglycemics: A Systematic Review and Critical Analysis of the Literature on Adherence, Persistence, and Health Outcomes.

INTRODUCTION: Improving real-world medication adherence to injectable antihyperglycemics in type 2 diabetes mellitus (T2DM) is a clinical challenge. Quantification of the level of adherence required to achieve a minimal clinically important difference (MCID) in glycemic control would assist in meeting this goal. The study objective was to review the literature regarding the relationships of medication adherence and persistence with health outcomes in adult T2DM patients using injectable antihyperglycemics. METHODS: Systematic searches were conducted using electronic databases to identify publications over the last decade. Publications were screened against established eligibility criteria. Study data were extracted, evaluated, and used to identify strengths, limitations, and gaps in current evidence. RESULTS: Eligibility criteria were met by 38 studies, and this report analyzed 34 studies related to glycemic control (n = 25), healthcare resource use (n = 9), and healthcare costs (n = 14). Eight of these studies examined adherence to glucagon-like peptide-1 receptor agonists (GLP-1 RA), including 1 study regarding adherence to GLP-1 RA or to insulin, and 1 study investigating a GLP-1 RA/insulin combination; the remaining studies involved insulin. Studies used a broad range of measures to classify adherence and persistence, and most measures were unable to reliably evaluate the complexities of patient behavior over time. Better adherence to injectable antihyperglycemic medications was generally found to be associated with improved glycemic control, although no studies attempted to identify a MCID. Although higher diabetes-related pharmacy and total healthcare costs were reported for adherent or persistent patients, these patients tended to have lower diabetes-related and all-cause medical costs. CONCLUSION: Results of this review confirmed the effectiveness of injectable antihyperglycemic medications for glycemic control, suggesting that there are clinical and financial consequences to nonadherence. Although attempts were made to quantify the effects of nonadherence, the interpretation of study results was limited by the lack of a MCID and inadequate study design. FUNDING: Novo Nordisk, Inc., Plainsboro Township, NJ, USA. Plain language summary available for this article.