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Jeff Schein,1 Martin Cloutier,2 Marjolaine Gauthier-Loiselle,2 Maryaline Catillon,3 Yan Meng,4 Beatrice Libchaber,2 Fanny Jiang,2 Ann Childress5 1Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, NJ, USA; 2Analysis Group, Inc, Montréal, QC, Canada; 3Analysis Group, Inc, New York, NY, USA; 4Analysis Group, Inc, London, UK; 5Center for Psychiatry and Behavioral Medicine, Las Vegas, NV, USACorrespondence: Maryaline Catillon, Analysis Group, Inc, 151 West 42nd Street, 23rd Floor, New York, NY, 10036, USA, Tel +1 857 222 6863, Email maryaline.catillon@analysisgroup.comBackground: Understanding patient preferences for treatments may facilitate shared decision-making. This study assessed adult patient preferences for attention-deficit/hyperactivity disorder (ADHD) treatments in a sample of 600 patients in the United States (US).Methods: A web-based discrete choice experiment (DCE) survey was conducted among treated adults with ADHD. Participants were recruited from Dynata’s US panel (06/22/2023-07/06/2023). Attributes and levels, identified based on clinical inputs and published data, included efficacy and safety. Participants’ preferences were estimated using conditional logistic regression. Willingness to trade-off and attributes’ relative importance were calculated. Overall preferences for treatment profiles approximating centanafadine, lisdexamfetamine, atomoxetine, and viloxazine were estimated using adjusted total utilities. Results were stratified by current treatment status. Sensitivity analyses including participants who passed validity tests were conducted.Results: Among the 600 participants (mean age 37.9 years; 66.2% female; 50.8% treated), all attributes had a statistically significant impact on preferences for ADHD treatments (p < 0.001); the most important attribute was improvement in ADHD symptoms (36%), followed by risks of nausea (25%), insomnia (20%), anxiety (8%), dry mouth (6%), and feeling jittery (5%). Together, safety attributes accounted for > 60% of relative importance in decision-making. Participants were willing to forgo 0.59, 0.57, 0.49, 0.32, and 0.17 percentage points of symptom improvement to achieve one-percentage-point reduced risk of insomnia, nausea, anxiety, feeling jittery, and dry mouth, respectively. Centanafadine profile had consistently higher adjusted total utilities than its comparators. Similar results were obtained in the subgroup and sensitivity analyses.Conclusion: Efficacy was the most important attribute for patients when making treatment decision, but taken together, AEs had greater relative importance than efficacy alone. Accordingly, a profile resembling that of centanafadine would be preferred by an average patient compared to key competitors due to its favorable safety profile. These findings may help improve treatment decision-making, enhance treatment satisfaction, and foster adherence.Keywords: ADHD, decision-making, discrete choice experiment, patient-centered care, patient satisfaction, patient preference, utility

Purpose: Evidence on treatment preferences of patients with moderate-to-severe atopic dermatitis (AD) in the United States (US) is limited and an assessment of treatment preferences in this group is warranted. Materials and methods: An online discrete choice experiment survey was conducted (June 2023) among US adults with self-reported moderate-to-severe AD or experience with systemic therapy who had inadequate response to topical treatments. Preference weights estimated from conditional logistic regression models were used to calculate willingness to trade off and attributes' relative importance (RI). Results: Participants ( N  = 300; mean age: 45 years; 70% females; 52% systemic therapy experienced) preferred treatments with higher efficacy, lower risk of adverse events (AEs), and less frequent blood tests ( p  < .05). Treatment attributes, from high to low RI, were itch control (38%), risk of cancer (23%), risk of respiratory infections (18%), risk of heart problems (11%), sustained improvement in skin appearance (5%), blood test frequency (3%), and frequency and mode of administration (2%); together, AE attributes accounted for more than half of the RI. Conclusions: Participants preferred AD treatments that maximize itch control while minimizing AE risks, whereas mode of administration had little impact on preferences. Understanding patients' preferences may help improve shared decision-making, potentially leading to enhanced patient satisfaction with treatment, increased engagement, and better clinical outcomes.

Introduction: Factors influencing attention-deficit/hyperactivity disorder (ADHD) treatment preferences have been studied among patients but not physicians in the United States (US) and Canada. This study assessed treatment preferences of physicians treating adult patients with ADHD in both countries., Methods: An online discrete choice experiment (DCE) was conducted (October 4-20, 2023) among physicians from Dynata's US and Canadian panel who treated adult patients with ADHD. Preference weights for efficacy (improvement in ADHD symptoms) and safety [risks of adverse events (AEs)] attributes were estimated using a conditional logistic regression model, and were used to calculate the willingness to trade-off and relative importance of the attributes., Results: Among 510 US and 347 Canadian physicians (64.1% and 69.2% male, respectively), improvement in ADHD symptoms had a significant positive impact, and the risks of AEs (except the risk of feeling jittery in Canada) had a significant negative impact on physician preferences for ADHD treatments. US physicians were willing to tradeoff 0.44, 0.35, 0.20, 0.17, and 0.17 percentage points of improvement in ADHD symptoms to avoid a one-percentage-point risk of insomnia, nausea, feeling jittery, anxiety, and dry mouth, respectively; among Canadian physicians, these were 0.31, 0.21, 0.12, 0.20, and 0.07, respectively. The relative importance of the efficacy versus safety attributes (i.e., the risks of AEs included in the DCE taken together) was 45.5% versus 54.5% in the US and 56.3% versus 43.7% in Canada., Conclusion: Efficacy was the most important single attribute for physicians treating adult patients with ADHD in both the US and Canada; however, the risks of AEs taken together had greater relative importance than efficacy alone among US but not Canadian physicians. These findings highlight potential discrepancies in physician and patient preferences based on existing evidence and underscore the importance of shared decision-making, which may in turn increase patients' treatment satisfaction., Competing Interests: Declarations Conflict of Interest Jeff Schein is an employee of Otsuka Pharmaceutical Development & Commercialization, Inc. Martin Cloutier, Marjolaine Gauthier-Loiselle, Maryaline Catillon, Yan Meng, Beatrice Libchaber, and Fanny Jiang are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Otsuka Pharmaceutical Development & Commercialization, Inc. Ann Childress received research support from Aardvark, Allergan, Axsome, Emalex, Akili, Cingulate, Corium, Ironshore, Les Laboratoires Servier, Lumos, Neurocentria, Otsuka, Purdue, Adlon, Sunovion, Tris, KemPharm, and Supernus; was on the advisory board of Corium, Otsuka, Tris, and Supernus; received consulting fees from Aardvark, Alora, Axsome, Aytu, Cingulate, Corium, Lumos, Medison Pharma, Neurocentria, Noven, Otsuka, Tris, KemPharm, Supernus, and Tulex; received speaker fees from Takeda, Corium, Ironshore, Tris, and Supernus; and received writing support from Otsuka, Takeda, Corium, Ironshore, Purdue, and Tris. Ethical Approval The study was approved by the Western Copernicus Group (WCG) Institutional Review Board (IRB; IRB number 20233279). The study is in accordance with the Declaration of Helsinki. , (© 2024. The Author(s).)

Objectives: To assess quality of life and outcomes associated with adverse effects (AEs) in pediatric patients receiving pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) and their parents/caregivers. Methods: An online survey was conducted (10/13/2023-10/20/2023) among parents/caregivers recruited from Dynata's U.S. panel who lived with a pediatric patient (6-17 years) currently treated for ADHD. Patient and parent/caregiver characteristics and outcomes were descriptively reported. Patients were considered to have AEs if they experienced symptoms/complications in the past 30 days that appeared, worsened, or remained unchanged after initiating their latest ADHD treatment. Regression analyses were used to estimate correlations between the number of AEs and key outcomes, including patients' health-related quality of life (HRQoL; based on the Pediatric Quality of Life Inventory) and parents/caregivers' work and activity impairments (based on Work Productivity and Activity Impairment: Caregiver) and mental health (based on Patient Health Questionnaire-4). Results: A total of 401 parents/caregivers from all U.S. regions completed the survey (caregiver median age: 38 years, 58.9% female; patient median age: 11 years; 37.7% female). In the 30 days prior to data collection, 66.8% of patients had AEs (overall mean: 1.2 AEs), with insomnia/sleep disturbances and decreased appetite/weight loss being the most frequently reported (14.2% and 11.7%, respectively). The number of AEs was significantly correlated with reduced patient's HRQoL (including reduced physical, emotional, and school functioning), increased parent/caregiver's work and activity impairment, and a higher likelihood of parents/caregivers having generalized anxiety disorder or major depressive disorder, respectively (all p < 0.001). Conclusions: AEs are common among pediatric patients receiving pharmacological treatment for ADHD and are associated with poorer quality of life and outcomes in pediatric patients and their parents/caregivers. Therapies with better safety profiles may help improve patient's HRQoL and parent/caregiver outcomes.

Aim: To compare long-term safety and efficacy outcomes of centanafadine versus lisdexamfetamine dimesylate (lisdexamfetamine), methylphenidate hydrochloride (methylphenidate) and atomoxetine hydrochloride (atomoxetine), respectively, in adults with attention-deficit/hyperactivity disorder (ADHD) using matching-adjusted indirect comparisons (MAICs). Patients & methods: Patient-level data from a centanafadine trial (NCT03605849) and published aggregate data from a lisdexamfetamine trial (NCT00337285), a methylphenidate trial (NCT00326300) and an atomoxetine trial (NCT00190736) were used. Patient characteristics were matched in each comparison using propensity score weighting. Study outcomes were assessed up to 52 weeks and included safety (rates of adverse events [AEs]) and efficacy (mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale [AISRS] or ADHD Rating Scale [ADHD-RS] score). Results: In all comparisons of matched populations, risks of AEs were statistically significantly lower with centanafadine or non-different between centanafadine and comparator; the largest differences in AE rates included upper respiratory tract infection (risk difference in percentage points: 18.75), insomnia (12.47) and dry mouth (12.33) versus lisdexamfetamine; decreased appetite (20.25), headache (18.53) and insomnia (12.65) versus methylphenidate; and nausea (26.18), dry mouth (25.07) and fatigue (13.95) versus atomoxetine (all p < 0.05). Centanafadine had a smaller reduction in the AISRS/ADHD-RS score versus lisdexamfetamine (6.15-point difference; p < 0.05) and no statistically significant difference in the change in AISRS score versus methylphenidate (1.75-point difference; p = 0.13) and versus atomoxetine (1.60-point difference; p = 0.21). Conclusion: At up to 52 weeks, centanafadine showed significantly lower incidence of several AEs than lisdexamfetamine, methylphenidate and atomoxetine; efficacy was lower than lisdexamfetamine and non-different from methylphenidate and atomoxetine.

Objective: To compare safety and efficacy of centanafadine versus methylphenidate hydrochloride extended release (ER; Concerta) in adults with ADHD., Methods: Without head-to-head trials, anchored matching-adjusted indirect comparisons (MAIC) of adverse event rates reported across trials and mean change from baseline in Adult ADHD Investigator Symptom Rating Scale (AISRS) score between centanafadine and methylphenidate hydrochloride ER were conducted. Pooled patient-level data from two centanafadine trials (NCT03605680/NCT03605836) and aggregate data from one published methylphenidate hydrochloride ER trial (NCT00937040) were used. Characteristics of individual patients from the centanafadine trials were matched to aggregate baseline characteristics from the methylphenidate hydrochloride ER trial using propensity score weighting. A sensitivity analysis assessed the robustness of the results to the capping of extreme weights (i.e. >99 th percentile)., Results: Compared with methylphenidate hydrochloride ER, centanafadine was associated with significantly lower risk of dry mouth (risk difference [RD] in percentage points: -11.95), initial insomnia (-11.10), decreased appetite (-8.05), anxiety (-5.39), palpitations (-5.25), and feeling jittery (-4.73) though a significantly smaller reduction in AISRS score (4.16-point). In the sensitivity analysis, the safety results were consistent with the primary analysis but there was no significant difference in efficacy between centanafadine and methylphenidate hydrochloride ER., Conclusion: In this MAIC, centanafadine had better safety and possibly lower efficacy than methylphenidate hydrochloride ER. While safety results were robust across analyses, there was no efficacy difference between centanafadine and methylphenidate hydrochloride ER in the sensitivity analysis. Considering its favorable safety profile, centanafadine may be preferred among patients for whom treatment-related adverse events are a concern.

Background: Attention-deficit/hyperactivity disorder (ADHD) has been shown to pose considerable clinical and economic burden; however, research quantifying the excess burden attributable to common psychiatric comorbidities of ADHD among pediatric patients is scarce. This study assessed the impact of anxiety and depression on healthcare resource utilization (HRU) and healthcare costs in pediatric patients with ADHD in the United States., Methods: Patients with ADHD aged 6-17 years were identified in the IQVIA PharMetrics Plus database (10/01/2015-09/30/2021). The index date was the date of initiation of a randomly selected ADHD treatment. Patients with ≥ 1 diagnosis for anxiety and/or depression during both the baseline (6 months pre-index) and study period (12 months post-index) were classified in the ADHD+anxiety/depression cohort; those without diagnoses for anxiety nor depression during both periods were classified in the ADHD-only cohort. Entropy balancing was used to create reweighted cohorts. All-cause HRU and healthcare costs during the study period were compared using regression analyses. Cost analyses were also performed in subgroups by comorbid conditions., Results: The reweighted ADHD-only cohort (N = 204,723) and ADHD+anxiety/depression cohort (N = 66,231) had similar characteristics (mean age: 11.9 years; 72.8% male; 56.2% had combined inattentive and hyperactive ADHD type). The ADHD+anxiety/depression cohort had higher HRU than the ADHD-only cohort (incidence rate ratios for inpatient admissions: 10.3; emergency room visits: 1.6; outpatient visits: 2.3; specialist visits: 5.3; and psychotherapy visits: 6.1; all p < 0.001). The higher HRU translated to greater all-cause healthcare costs; the mean per-patient-per-year (PPPY) costs in the ADHD-only cohort vs. ADHD+anxiety/depression cohort was $3,988 vs. $8,682 (p < 0.001). All-cause healthcare costs were highest when both comorbidities were present; among patients with ADHD who had only anxiety, only depression, and both anxiety and depression, the mean all-cause healthcare costs were $7,309, $9,901, and $13,785 PPPY, respectively (all p < 0.001)., Conclusions: Comorbid anxiety and depression was associated with significantly increased risk of HRU and higher healthcare costs among pediatric patients with ADHD; the presence of both comorbid conditions resulted in 3.5 times higher costs relative to ADHD alone. These findings underscore the need to co-manage ADHD and psychiatric comorbidities to help mitigate the substantial burden borne by patients and the healthcare system., (© 2024. The Author(s).)

Background: Head-to-head trials comparing centanafadine, an investigational therapy for adults with attention-deficit/hyperactivity disorder (ADHD), with other treatment options are lacking., Objective: To compare safety and efficacy outcomes of centanafadine sustained-release vs lisdexamfetamine dimesylate (lisdexamfetamine), atomoxetine hydrochloride (atomoxetine), and viloxazine extended-release (viloxazine ER), respectively, using matching-adjusted indirect comparison (MAIC)., Methods: This MAIC included patient-level data pooled from 2 centanafadine trials (NCT03605680 and NCT03605836) and published aggregate data from comparable trials of 3 comparators-lisdexamfetamine (NCT00334880), atomoxetine (NCT00190736), and viloxazine ER (NCT04016779)-in adult patients with ADHD. Propensity score weighting was used to match characteristics of individual patients from the centanafadine trials to aggregate baseline characteristics from the respective comparator trials. Safety outcomes were rates of adverse events for which information was available in the centanafadine and respective comparator trials. Efficacy outcome was mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale (AISRS) score (ADHD Rating Scale [ADHD-RS] was used as proxy in the comparison with lisdexamfetamine). Anchored indirect comparisons were conducted across matched populations of the centanafadine and respective comparator trials., Results: After matching, baseline characteristics in the centanafadine trials were the same as those in the respective comparator trials. Compared with lisdexamfetamine, centanafadine was associated with a significantly lower risk of lack of appetite (risk difference [RD] in percentage points: 23.42), dry mouth (19.27), insomnia (15.35), anxiety (5.21), nausea (4.90), feeling jittery (3.70), and diarrhea (3.47) (all P < 0.05) but a smaller reduction in the AISRS/ADHD-RS score (6.58-point difference; P < 0.05). Compared with atomoxetine, centanafadine was associated with a significantly lower risk of nausea (RD in percentage points: 18.64), dry mouth (17.44), fatigue (9.21), erectile dysfunction (6.76), lack of appetite (6.71), and urinary hesitation (5.84) (all P < 0.05) and no statistically significant difference in the change in AISRS score. Compared with viloxazine ER, centanafadine was associated with a significantly lower risk of fatigue (RD in percentage points: 11.07), insomnia (10.67), nausea (7.57), and constipation (4.63) (all P < 0.05) and no statistically significant difference in the change in AISRS score., Conclusions: In an anchored MAIC, centanafadine showed a significantly better short-term safety profile than lisdexamfetamine, atomoxetine, and viloxazine ER; efficacy was lower than with lisdexamfetamine and comparable (ie, nondifferent) with atomoxetine and viloxazine ER. This MAIC provides important insights on the relative safety and efficacy of common treatment options to help inform treatment decisions in adults with ADHD. Safety assessment was limited to rates of adverse events reported in both trials of a given comparison., Study Registration Numbers: NCT03605680, NCT03605836, NCT00334880, NCT00190736, and NCT04016779.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous condition with extensive psychiatric comorbidities. ADHD has been associated with substantial clinical and economic burden; however, little is known about the incremental burden specifically attributable to psychiatric comorbidities of ADHD in adults., Objective: To assess the impact of psychiatric comorbidities, specifically anxiety and depression, on health care resource utilization (HRU) and costs in treated adults with ADHD in the United States., Methods: A retrospective case-cohort study was conducted. Adults with ADHD were identified in the IQVIA PharMetrics Plus database (10/01/2015-09/30/2021). The index date was defined as the date of initiation of a randomly selected ADHD treatment. The baseline period was defined as the 6 months prior to the index date, and the study period as the 12 months following the index date. Patients with at least 1 diagnosis for anxiety and/or depression during both the baseline and study periods were classified in the ADHD+anxiety/depression cohort, whereas those without diagnoses for anxiety or depression at any time were classified in the ADHD-only cohort. Entropy balancing was used to create reweighted cohorts with similar baseline characteristics. All-cause HRU and health care costs were assessed during the study period and compared between cohorts using regression analyses. Cost analyses were also conducted in subgroups stratified by comorbid conditions., Results: After reweighting, patients in the ADHD-only cohort (N = 276,906) and ADHD+anxiety/depression cohort (N = 217,944) had similar characteristics (mean age 34.1 years; 54.8% male). All-cause HRU was higher in the ADHD+anxiety/depression cohort than the ADHD-only cohort (incidence rate ratios for inpatient admissions: 4.5, emergency department visits: 1.8, outpatient visits: 2.0, and psychotherapy visits: 6.4; all P < 0.01). All-cause health care costs were more than 2 times higher in the ADHD+anxiety/depression cohort than the ADHD-only cohort (mean per-patient per-year [PPPY] costs in ADHD-only vs ADHD+anxiety/depression cohort: $5,335 vs $11,315; P < 0.01). Among the ADHD+anxiety/depression cohort, average all-cause health care costs were $9,233, $10,651, and $15,610 PPPY among subgroup of patients with ADHD and only anxiety, only depression, and both anxiety and depression, respectively., Conclusions: Comorbid anxiety and depression is associated with additional HRU and costs burden in patients with ADHD. Comanagement of these conditions is important and has the potential to alleviate the burden experienced by patients and the health care system.

Introduction: Invasive Escherichia coli disease (IED) can lead to sepsis and death and is associated with a substantial burden. Yet, there is scarce information on the burden of IED in Asian patients., Methods: This retrospective study used US hospital data from the PINC AI™ Healthcare database (October 2015-March 2020) to identify IED cases among patients aged ≥ 60 years. IED was defined as a positive E. coli culture in blood or other normally sterile body site (group 1 IED) or positive culture of E. coli in urine with signs of sepsis (group 2 IED). Eligible patients with IED were classified into Asian and non-Asian cohorts based on their reported race. Entropy balancing was used to create cohorts with similar characteristics. Outcomes following IED were descriptively reported in the balanced cohorts., Results: A total of 646 Asian and 19,127 non-Asian patients with IED were included (median age 79 years; 68% female after balancing). For both cohorts, most IED encounters had community-onset (> 95%) and required hospitalization (Asian 96%, mean duration 6.9 days; non-Asian 95%, mean duration 6.8 days), with frequent admission to intensive care (Asian 35%, mean duration 3.3 days; non-Asian 34%, mean duration 3.5 days), all standardized differences [SD] < 0.20. Compared to non-Asian patients, Asian patients were more likely to be discharged home (54% vs. 43%; SD = 0.22), and less likely to be discharged to a skilled nursing facility (24% vs. 31%; SD = 0.16). In-hospital fatality rates during the IED encounter were similar across cohorts (Asian 9%, non-Asian 10%; SD = 0.01). Most E. coli isolates showed resistance to ≥ 1 antibiotic (Asian 61%; non-Asian 64%) and 36% to ≥ 3 antibiotic classes (all SD < 0.20)., Conclusion: IED is associated with a substantial burden, including need for intensive care and considerable mortality, in Asian patients in the USA that is consistent with that observed for non-Asian patients., (© 2024. The Author(s).)

Objective: Attention-deficit/hyperactivity disorder (ADHD) medication is frequently associated with adverse events (AEs), but limited real-world data exist regarding their costs from a payer's perspective. Therefore, this study evaluated the healthcare costs associated with common AEs among adult patients treated for ADHD in the US., Methods: Eligible adults treated for ADHD were identified from a large US claims database (1 October 2015-30 September 2021). A retrospective cohort study design was used to assess excess healthcare costs and costs directly related to AE-specific claims per-patient-per-month (PPPM) associated with 10 selected AEs during ADHD treatment. To account for all costs associated with the AE, treatment episodes with a given AE were compared to similar treatment episodes without this AE. Entropy balancing was used to create cohorts with similar characteristics. Studied AEs were selected based on their prevalence in clinical trials for common ADHD medications and were identified from ICD-10-CM diagnosis codes recorded in claims., Results: Among the 461,464 patients included (mean age: 34.2 years; 45.5% males), 49.4% had ≥1 AE during their treatment episode. Treatment episodes with AEs were associated with statistically significant AE-specific medical costs (erectile dysfunction: $57; fatigue: $82; dry mouth: $90; diarrhea: $162; insomnia: $147; anxiety: $281; nausea: $299; constipation: $356; urinary hesitation: $491; feeling jittery: $723) and excess healthcare costs PPPM (erectile dysfunction: $120, fatigue: $248, insomnia: $265, anxiety: $380, diarrhea: $441, dry mouth: $485, nausea: $709, constipation: $802, urinary hesitation: $1,105, feeling jittery: $1,160; p  < .05)., Limitations: AEs were identified based on recorded diagnosis on medical claims and likely represent more severe AEs. Therefore, costs may not be representative of milder AEs., Conclusions: This study found that AEs occurring during ADHD treatment episodes are associated with significant healthcare costs. This highlights the potential of treatments with favorable safety profiles to alleviate the burden experienced by patients and the healthcare system.

Aims: To describe and compare clinical characteristics, healthcare costs, and institutionalization/mortality outcomes among patients with and without agitation associated with Alzheimer's dementia (AAD)., Methods: Data from the Reliant Medical Group database (01/01/2016-03/31/2020) were used, including claims, electronic medical records, and clinical information/physician notes abstracted from medical charts. Patients aged ≥55 years with Alzheimer's dementia (AD) were observed during a randomly selected 12-month study period after AD diagnosis. Using information recorded in medical charts, patients were classified into cohorts based on experiencing (agitation cohort) and not experiencing (no agitation cohort) agitated behaviours during the study period. Entropy balancing was used to create reweighted cohorts with similar characteristics. Study outcomes (patient demographic and clinical characteristics, treatments received, healthcare costs, institutionalization and death events) were compared between cohorts; agitation characteristics were described for the agitation cohort only., Results: Among 711 patients included in the study, 240 were classified in the agitation cohort and 471 in the no agitation cohort. After reweighting, several comorbidities were more frequently observed in the agitation versus no agitation cohort, including infection, depression, and altered mental status. Use of antidepressants, anticonvulsants, antipsychotics, and antianxiety medications was more common in the agitation versus no agitation cohort. Common agitated behaviours included hitting (20.8%), pacing/aimless wandering (17.5%), and cursing/verbal aggression (15.0%). Total all-cause healthcare costs were $4287 per-patient-per-year higher in the agitation cohort versus no agitation cohort ( p  = 0.04), driven by higher inpatient costs. Death was more common and time to death and institutionalization were shorter in the agitation versus no agitation cohort., Limitations: Results may not be generalizable to the US population with AD., Conclusions: Among patients with AD, agitation was associated with shorter time to death/institutionalization and increased comorbidities, medication use, and healthcare costs, highlighting the additional clinical and economic burden that agitation poses to patients and the healthcare system.

Background: The aim of this study was to assess health care resource utilization (HRU) and costs associated with delayed pulmonary arterial hypertension (PAH) diagnosis in the United States., Methods: Eligible adults with newly diagnosed PAH from Optum's de-identified Clinformatics ® Data Mart Database (2016-2021) were assigned to mutually exclusive cohorts based on time between first PAH-related symptom and first PAH diagnosis (i.e., ≤12 months' delay, >12 to ≤24 months' delay, >24 months' delay). All-cause HRU and health care costs per patient per month (PPPM) were assessed during the first year following diagnosis and compared across cohorts using regression analysis adjusted for baseline covariates. Sensitivity analyses were conducted to assess outcomes during all available follow-up post-diagnosis., Results: Among 538 patients (mean age: 65.6 years; 60.6% female), 60.8% had ≤12 months' delay, 23.4% had a delay of >12 to ≤24 months, and 15.8% had >24 months' delay. Compared with ≤12 months, delays of >12 to ≤24 months and >24 months were associated with increased hospitalizations (incidence rate ratio [95% confidence interval]: 1.40 [1.11-1.71] vs 1.71 [1.29-2.12]) and outpatient visits (1.17 [1.06-1.30] vs 1.26 [1.08-1.41]). Longer delays were also associated with more intensive care unit (ICU) stays and 30-day readmissions. Diagnosis delays translated into excess costs PPPM of US$3986 [1439-6436] for >12 to ≤24 months and US$5366 [2107-8524] for >24 months compared with ≤12 months' delay; increased hospitalization costs (US$3248 [1108-5135] and US$4048 [1401-6342], respectively) being the driver. Sensitivity analyses yielded similar trends., Conclusions: Delayed PAH diagnosis is associated with significant incremental economic burden post-diagnosis, driven by hospitalizations including ICU stays and 30-day readmissions, highlighting the need for increased awareness and a potential benefit of earlier screening., (© 2023. The Author(s).)

Background: Knowledge of risk factors for attention-deficit/hyperactivity disorder (ADHD) may facilitate early diagnosis; however, studies examining a broad range of potential risk factors for ADHD in adults are limited. This study aimed to identify risk factors associated with newly diagnosed ADHD among adults in the United States (US)., Methods: Eligible adults from the IQVIA PharMetrics® Plus database (10/01/2015-09/30/2021) were classified into the ADHD cohort if they had ≥ 2 ADHD diagnoses (index date: first ADHD diagnosis) and into the non-ADHD cohort if they had no observed ADHD diagnosis (index date: random date) with a 1:3 case-to-control ratio. Risk factors for newly diagnosed ADHD were assessed during the 12-month baseline period; logistic regression with stepwise variable selection was used to assess statistically significant association. The combined impact of selected risk factors was explored using common patient profiles., Results: A total of 337,034 patients were included in the ADHD cohort (mean age 35.2 years; 54.5% female) and 1,011,102 in the non-ADHD cohort (mean age 44.0 years; 52.4% female). During the baseline period, the most frequent mental health comorbidities in the ADHD and non-ADHD cohorts were anxiety disorders (34.4% and 11.1%) and depressive disorders (27.9% and 7.8%). Accordingly, a higher proportion of patients in the ADHD cohort received antianxiety agents (20.6% and 8.3%) and antidepressants (40.9% and 15.8%). Key risk factors associated with a significantly increased probability of ADHD included the number of mental health comorbidities (odds ratio [OR] for 1 comorbidity: 1.41; ≥2 comorbidities: 1.45), along with certain mental health comorbidities (e.g., feeding and eating disorders [OR: 1.88], bipolar disorders [OR: 1.50], depressive disorders [OR: 1.37], trauma- and stressor-related disorders [OR: 1.27], anxiety disorders [OR: 1.24]), use of antidepressants (OR: 1.87) and antianxiety agents (OR: 1.40), and having ≥ 1 psychotherapy visit (OR: 1.70), ≥ 1 specialist visit (OR: 1.30), and ≥ 10 outpatient visits (OR: 1.51) (all p < 0.05). The predicted risk of ADHD for patients with treated anxiety and depressive disorders was 81.9%., Conclusions: Mental health comorbidities and related treatments are significantly associated with newly diagnosed ADHD in US adults. Screening for patients with risk factors for ADHD may allow early diagnosis and appropriate management., (© 2023. The Author(s).)

Introduction: Connective tissue disorders (CTDs) are the most frequent diseases associated with pulmonary arterial hypertension (PAH). Despite advances in treatment, the prognosis of CTD-related PAH remains poor. To help identify areas for improvement in the management of CTD-related PAH, this study assessed real-world PAH treatment patterns in this population in the US., Methods: Eligible adult patients with PAH initiated on a PAH treatment (index date: 1st initiation date) were identified from Optum's de-identified Clinformatics ® Data Mart Database (10/01/2015-09/30/2021) and categorized into mutually exclusive cohorts (CTD + PAH; PAH) based on the presence of CTD diagnosis claims. Treatment patterns were assessed from the index date to the earliest of death or end of continuous insurance eligibility, or data availability. Treatment persistence was assessed using Kaplan-Meier analysis., Results: A total of 4751 patients were included (CTD + PAH: n = 728, mean follow-up of 18.8 months; PAH: n = 4023, mean follow-up of 19.6 months). For both cohorts, the most common first treatment regimens were sildenafil (CTD + PAH: 38.7%; PAH: 51.5%), tadalafil (10.0%; 9.4%), and macitentan (8.1%; 5.4%) monotherapy; these were also the most frequent agents included in any of the first 3 treatment regimens. Combination therapy was more frequent in the CTD + PAH versus PAH cohort (any regimen: 40.9% vs. 27.2%; 1st treatment regimen: 26.9% vs. 18.5%; 2nd: 52.8% vs. 42.0%; 3rd: 55.2% vs. 48.5%). Treatment persistence was similar across cohorts and the first three treatment regimens, with persistence rates ranging from 42.6 to 49.7% at 12 months., Conclusions: Treatment patterns were generally similar between the CTD + PAH and PAH cohorts, although combination therapy was more frequent in the CTD + PAH cohort. Both cohorts may benefit from broader use of all available PAH treatment classes, including combination therapy. Considering the life-threatening nature of PAH, our findings also highlight the need to address the low persistence rates with PAH therapies regardless of etiology., (© 2023. The Author(s).)

Objective: To assess the predictive accuracy of code-based algorithms for identifying invasive Escherichia coli ( E. coli) disease (IED) among inpatient encounters in US hospitals., Methods: The PINC AI Healthcare Database (10/01/2015-03/31/2020) was used to assess the performance of six published code-based algorithms to identify IED cases among inpatient encounters. Case-confirmed IEDs were identified based on microbiological confirmation of E. coli in a normally sterile body site (Group 1) or in urine with signs of sepsis (Group 2). Code-based algorithm performance was assessed overall, and separately for Group 1 and Group 2 based on sensitivity, specificity, positive and negative predictive value (PPV and NPV) and F1 score. The improvement in performance of refinements to the best-performing algorithm was also assessed., Results: Among 2,595,983 encounters, 97,453 (3.8%) were case-confirmed IED (Group 1: 60.9%; Group 2: 39.1%). Across algorithms, specificity and NPV were excellent (>97%) for all but one algorithm, but there was a trade-off between sensitivity and PPV. The algorithm with the most balanced performance characteristics included diagnosis codes for: (1) infectious disease due to E. coli OR (2) sepsis/bacteremia/organ dysfunction combined with unspecified E. coli infection and no other concomitant non- E. coli invasive disease (sensitivity: 56.9%; PPV: 56.4%). Across subgroups, the algorithms achieved lower algorithm performance for Group 2 (sensitivity: 9.9%-61.1%; PPV: 3.8%-16.0%)., Conclusions: This study assessed code-based algorithms to identify IED during inpatient encounters in a large US hospital database. Such algorithms could be useful to identify IED in healthcare databases that lack information on microbiology data.

Background: Invasive extraintestinal pathogenic Escherichia coli disease (IED) can lead to severe outcomes, particularly among older adults. However, the clinical burden of IED in the U.S. has not been well characterized., Methods: IED encounters among patients ≥ 60 years old were identified using the PINC AI™ Healthcare Database (10/01/2015-03/31/2020) by either a positive E. coli culture in blood or another normally sterile body site and ≥ 1 sign of systemic inflammatory response syndrome or signs of sepsis, or a positive E. coli culture in urine with urinary tract infection and signs of sepsis. Medical resource utilization, clinical outcomes, and E. coli isolate characteristics were descriptively reported during the first IED encounter and during the following year (observation period)., Results: Overall, 19,773 patients with IED were included (mean age: 76.8 years; 67.4% female; 78.5% with signs of sepsis). Most encounters involved community-onset IED (94.3%) and required hospitalization (96.5%; mean duration: 6.9 days), with 32.4% of patients being admitted to the intensive care unit (mean duration: 3.7 days). Most E. coli isolates were resistant to ≥ 1 antibiotic category (61.7%) and 34.4% were resistant to ≥ 3 antibiotic categories. Following their first IED encounter, 34.8% of patients were transferred to a skilled nursing/intermediate care facility, whereas 6.8% had died. During the observation period, 36.8% of patients were rehospitalized, 2.4% had IED recurrence, and in-hospital death increased to 10.9%., Conclusions: IED is associated with substantial clinical burden at first encounter with considerable long-term consequences. Findings demonstrate the need for increased IED awareness and highlight potential benefits of prevention., (© 2023. BioMed Central Ltd., part of Springer Nature.)

BACKGROUND: Although invasive Escherichia coli disease (IED) can lead to severe clinical outcomes, little is known about the associated medical resource use and cost burden of IED in US hospitals. OBJECTIVE: To comprehensively describe medical resource use and costs associated with IED during the initial IED event and over the subsequent 12 months. METHODS: Patients aged 60 years or older with 1 or more IED encounters were identified from the PINC AI Healthcare US hospital database (October 1, 2015, to March 31, 2020). The index encounter was defined as the first encounter with a positive E coli culture in a normally sterile site (group 1 IED) or positive E coli culture in urine with signs of sepsis (group 2 IED). Encounters with a positive culture from other bacteria or fungal pathogens were excluded. Outcomes were descriptively reported between admission and discharge for the index encounter and more than 1 - year post-index discharge. Medical resource use and costs included inpatient admissions and outpatient hospital services; costs were reported from a hospital's perspective (ie, charged amount) in 2021 USD. RESULTS: A total of 19,773 patients were identified (group 1 IED = 51.8%; group 2 IED = 48.2%). Mean age was 76.8 years, 67.4% were female, and 82.1% were White. Most index encounters were community-onset (94.3%) and led to hospitalization (96.5%) (mean inpatient days = 6.9 days). During the 1 - year post-index, 36.8% of patients had 1 or more all-cause hospitalizations. Mean [median] total all-cause hospital costs (as captured through the PINC AI Healthcare database) amounted to $16,760 [$11,340] during the index encounter and $10,942 [$804] during the 1 - year post-index; these costs were higher in the presence of sepsis and multidrug resistance and among hospital-onset IED. CONCLUSIONS: IED is associated with a substantial medical resource use and economic burden both during the initial encounter and over the following year in older adults. This highlights the critical need and potential benefits of preventive measures that may reduce the incidence of IED and associated economic burden. DISCLOSURES: This study was funded by Janssen Global Services, LLC. Dr Hernandez-Pastor is an employee of Janssen Pharmaceutica NV. Dr Geurtsen is an employee of Janssen Vaccines & Prevention BV. Dr Baugh is an employee of Janssen Research & Development, LLC. Dr El Khoury is an employee of Janssen Global Services, LLC. Dr Kalu and Dr Krishnarajah are employees of Janssen Scientific Affairs, LLC. Dr Gauthier-Loiselle, Ms Bungay, and Mr Cloutier are employees of Analysis Group, Inc., a consulting company that provided paid consulting services to Janssen Global Services, LLC. Dr Saade received consultation and speaker fees from Janssen.

Pulmonary arterial hypertension (PAH) is commonly associated with connective tissue disorders (CTDs). This study provides a contemporary assessment of the economic burden of CTD + PAH and PAH in the United States. Eligible adult patients identified from Optum's deidentified Clinformatics® Data Mart Database (10/01/2015-09/30/2021) were classified into mutually exclusive cohorts based on recorded diagnoses: (1) CTD + PAH, (2) PAH, (3) CTD, (4) control without CTD/PAH. The index date was a randomly selected diagnosis date for PAH (CTD + PAH, PAH cohorts) or CTD (CTD cohort), or a random date (control cohort). Entropy balancing was used to balance characteristics across cohorts. Healthcare costs and healthcare resource utilization (HRU) per patient per month (PPPM) were assessed for ≤12 months postindex and compared among balanced cohorts. A total of 552,900 patients were included (CTD + PAH: n  = 1876; PAH: n  = 8177; CTD: n  = 209,156; control: n  = 333,691). Average total all-cause costs were higher for CTD + PAH than PAH cohort ($16,854 vs. $15,686 PPPM; p  = 0.02); both cohorts incurred higher costs than CTD and control cohorts ($4476 and $2170 PPPM; all p  < 0.001). Average HRU PPPM was similar between CTD + PAH and PAH cohorts (inpatient stay: 0.15 vs. 0.15, outpatient visits: 4.23 vs. 4.11; all p  > 0.05), while CTD and control cohorts incurred less HRU (inpatient stay: 0.07 and 0.03, outpatient visits: 2.67 and 1.69; all p  < 0.001). CTD + PAH and PAH are associated with a substantial economic burden. The incremental burden attributable to PAH versus the general population and patients with CTD without PAH highlights significant unmet needs among PAH patients., Competing Interests: YT, SP, VF, and HG are employees of Janssen Scientific Affairs, LLC and may own stock/stock options. MGL, AMM, SL, MC, and PL are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC, which funded the development and conduct of this study and manuscript., (© 2023 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Objective: Describe symptoms associated with ADHD/treatment-related adverse side effects among adults with ADHD in the US and assess their impact on quality of life (QoL) and work productivity., Methods: An online survey among adults receiving ADHD medications in the US was conducted to collect information relating to symptoms associated with ADHD/treatment-related adverse side effects. Participants were recruited from the panel of a well-established market research firm, Dynata, from 26 July to 30 July 2021 and were included in the study if they met the eligibility criteria and were willing to participate in the survey. Correlations between symptoms and key outcomes (QoL/employment/work impairment) were estimated using linear regression analyses., Results: Of 585 participants, 95.2% experienced ≥1 symptom associated with ADHD/treatment-related adverse side effects in the past month (average = 5.8 symptoms). The number of symptoms was significantly correlated with reduced QoL, reduced probability of being employed, and increased work/activity impairment. Among subgroups with insomnia/other sleep disturbances and emotional impulsivity/mood lability, 50.4% and 44.7% reported their symptoms had "a lot" or "extremely" negative impact on their overall well-being, respectively., Conclusions: Symptoms associated with ADHD/treatment-related adverse side effects are common and have a substantial negative impact on QoL and reduces patients' probability of employment. Improved management of ADHD/treatment-related adverse side effects and more tolerable treatment options have the potential to improve QoL and work productivity among adults with ADHD.

Introduction: This study aimed to examine the reasons underlying treatment changes among pediatric patients with attention-deficit/hyperactivity disorder (ADHD)., Methods: Data were obtained through online medical chart abstraction (08/2021-09/2021). Eligible patients with ADHD had initiated a treatment regimen at ages 6-17 and within 1-5 years of chart abstraction. Reasons contributing to treatment changes were analyzed for a randomly selected treatment episode. ADHD/treatment-related complication rate was also described. Results were reported overall and among children (ages 6-12) and adolescents (ages 13-17), separately. Physicians' perspective on adherence among their child, adolescent, and adult patients was assessed through an online survey., Results: A total of 156 physicians abstracted 434 patient charts (235 children + 199 adolescents). Mean patient age was 11.3 years, and 68.7% were male. Inadequate/suboptimal symptom management was the most common reason for treatment discontinuation (50/83 [60.2%]), add-on (17/21 [81.0%]), and dose increase (189/237 [79.7%]). Patient/parent/family attitude/dislike of medication and ADHD/treatment-related complications were common reasons for treatment discontinuation, add-on, switch, and dose decrease. Overall, 42.4% of patients had ≥ 1 documented ADHD/treatment-related complication, insomnia/sleep disturbances being the most common (9.7%). Among patients with ≥ 1 complication, 75.5% reported the experience/fear of complications had a negative impact on their treatment adherence. Results were similar among children and adolescents. Physicians reported taking actions toward patients' non-adherence by further educating patients, closer monitoring, and changing the prescribed ADHD medication., Conclusion: Lack of effectiveness and ADHD/treatment-related complications are important reasons for treatment changes among children and adolescents with ADHD, highlighting the need for more effective and tolerable treatments to mitigate the burden of ADHD., (© 2022. The Author(s).)

Objective: This study aimed to develop and validate a predictive algorithm for unsatisfactory response to initial pulmonary arterial hypertension (PAH) therapy using health insurance claims., Methods: Adult patients with PAH initiated on a first PAH therapy (index date) were identified from Optum's de-identified Clinformatics Data Mart Database (1/1/2010-12/31/2019). A random survival forest algorithm was developed using patient-month data and predicted the "survival function" (i.e. risk of not having unsatisfactory response) over time. For each patient-month observation, risk factors were assessed in the 12 months prior. Unsatisfactory response was defined as the first instance of (1) new PAH therapy, (2) PAH-related hospitalization or emergency room visit, (3) lung transplant or atrial septostomy, (4) PAH-related death or (5) chronic oxygen therapy initiation. To facilitate use in clinical practice, a simplified risk score was also developed based on a linear combination of the most important risk factors identified in the algorithm., Results: In total, 4781 patients were included (median age = 69.0 years; 58.6% female). Over a median follow-up of 14.0 months, 3169 (66.3%) had an unsatisfactory response. The most important risk factors included in the algorithm were healthcare resource use (i.e. PAH-related outpatient visits, pulmonologist visits, cardiologist visits, all-cause hospitalizations), time since first PAH diagnosis, time since index date, Charlson Comorbidity Index, dyspnea, and age. Predictive accuracy was good for the full algorithm (C-statistic: 0.732) but was slightly lower for the simplified risk score (C-statistic: 0.668)., Conclusion: The present claims-based algorithm performed well in predicting time to unsatisfactory response following initial PAH therapy.

Rationale & Objective: Chronic kidney disease (CKD) has a far-reaching impact on both patients and care partners, which can be further compounded by frequent complications such as anemia. This study assessed the burden experienced by patients with CKD and the care partners of patients with CKD, with and without anemia., Study Design: Online survey., Setting & Participants: Adult patients with CKD and the care partners of adult patients with CKD living in the United States were recruited through the American Association of Kidney Patients and a third-party online panel (January 9, 2020-March 12, 2020)., Outcomes: Patient and care partner characteristics, care received or provided; health-related quality of life, and work productivity., Analytical Approach: Descriptive statistics were reported separately based on the presence or absence of anemia., Results: In total, 410 patients (anemia: n=190, no anemia: n=220) and 258 care partners (anemia: n=110, no anemia: n=148) completed the survey. Most patients reported receiving paid or unpaid care because of their health condition (anemia: 58.9%, no anemia: 50.9%), with an overall average of 14.2 and 11.3 h/wk among the anemia and no anemia patients, respectively. The care partners also reported providing numerous hours of care (anemia: 33.6 h/wk, no anemia: 38.0 h/wk), especially care partners living with their care recipient (anemia: 52.6 h/wk, no anemia: 42.8 h/wk). Among the patients, those with anemia reported a numerically lower average health-related quality of life (Functional Assessment of Cancer Therapy-Anemia score, anemia: 110.1; no anemia: 121.6). Most care partners reported a severe or very severe burden (Burden Scale for Family Caregivers-Short Version score≥15, anemia: 69.1%; no anemia: 58.8%). The work productivity impairment was substantial among employed patients (anemia: 44.9%, no anemia: 35.4%) and employed care partners (anemia: 47.9%, no anemia: 40.7%)., Limitations: The survey results may have been subject to selection and recall biases; moreover, the observational nature of the study does not allow for causal inferences., Conclusions: Patients with CKD and the care partners of patients with CKD experience a considerable burden, especially when anemia is present., (© 2022 The Authors.)