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BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with substantial clinical burden as individuals transition to adulthood, including higher rates of comorbidities, mortality, incarceration, and psychiatric hospitalizations than in individuals without ADHD. These higher rates likely contribute to substantial economic burden as well. OBJECTIVE: To provide a comprehensive evaluation of the economic burden associated with ADHD in the US adult population. METHODS: Direct health care costs were obtained by using claims data from the IBM MarketScan Research Databases (January 1, 2017, through December 31, 2018). Direct non-health care costs and indirect costs were estimated on the basis of the literature and government publications. Excess costs incurred by adults with ADHD during 2018 were evaluated from a societal perspective; per-patient costs were extrapolated to the national level. RESULTS: An estimated 8.7 million adults live with ADHD in the United States, resulting in a total societal excess cost attributable to ADHD of $122.8 billion ($14,092 per adult). Excess costs of unemployment ($66.8 billion; 54.4%) comprised the largest proportion of the total, followed by productivity loss ($28.8 billion; 23.4%) and health care services ($14.3 billion; 11.6%). CONCLUSIONS: ADHD in adults is associated with substantial economic burden. DISCLOSURES: This study was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. (Otsuka). The study sponsor contributed to and approved the study design, participated in the interpretation of data, and reviewed and approved the manuscript. Schein is an employee of Otsuka. Gagnon-Sanschagrin, Davidson, Kinkead, Cloutier, Guerin, and Lefebvre are employees of Analysis Group, Inc., a consulting company that provided paid consulting services to Otsuka to develop and conduct this study and write the manuscript. Adler has received research support from Shire/Takeda, Sunovion, and Otsuka; consulting fees from Bracket, Shire/Takeda, Sunovion, Otsuka, the State University of New York (SUNY), the National Football League (NFL), and Major League Baseball (MLB); and royalty payments (as inventor) from New York University (NYU) for license of adult ADHD scales and training materials. Childress has received research support from Allergan, Takeda/Shire, Emalex, Akili, Ironshore, Arbor, Aevi Genomic Medicine, Neos Therapeutics, Otsuka, Pfizer, Purdue, Rhodes, Sunovion, Tris, KemPharm, Supernus, and the US Food and Drug Administration; was on the advisory board of Takeda/Shire, Akili, Arbor, Cingulate, Ironshore, Neos Therapeutics, Otsuka, Pfizer, Purdue, Adlon, Rhodes, Sunovion, Tris, Supernus, and Corium; received consulting fees from Arbor, Ironshore, Neos Therapeutics, Purdue, Rhodes, Sunovion, Tris, KemPharm, Supernus, Corium, Jazz, and Tulex Pharma; received speaker fees from Takeda/Shire, Arbor, Ironshore, Neos Therapeutics, Pfizer, Tris, and Supernus; and received writing support from Takeda/Shire, Arbor, Ironshore, Neos Therapeutics, Pfizer, Purdue, Rhodes, Sunovion, and Tris. Part of the material in this study was presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2021 Virtual Meeting; May 17-20, 2021.

Introduction Spinal muscular atrophy (SMA) is a rare, genetic neuromuscular disorder caused by deletion/mutation of the survival motor neuron 1 gene, characterized by progressive loss of motor neurons, resulting in increasing muscular weakness, deteriorating motor function, and, in its most severe form, death before 2 years. Nusinersen, an antisense oligonucleotide that increases expression of the functional SMN protein, was approved for SMA by US and European regulatory agencies in 2016 and 2017, respectively. The indicated regimen requires intrathecal injections every 4 months, following the first four injections during the loading phase. Adherence is integral to treatment success. Adherence to nusinersen may pose particular challenges as most patients with SMA are young children who require complex multidisciplinary care (including ongoing intrathecal treatment administration and potential specialized anesthetic and surgical procedures) at specialized centers. However, real-world data on adherence to nusinersen are limited. Methods We conducted a retrospective claims database analysis from December 23, 2016, to November 20, 2019, to study nusinersen adherence and discontinuation/persistence in US patients with SMA types 1–3 who completed the loading phase, and to determine the impact of non-adherence or treatment discontinuation on SMA-related comorbidities, health care resource utilization (HCRU), and costs. Results We identified 23 patients with SMA type 1, 41 patients with SMA type 2, and 260 patients with SMA type 3 who had completed the loading phase. Deviations from the indicated nusinersen treatment schedule were frequent in real-world usage, with most patients receiving ≥1 dose outside the scheduled interval. Across SMA types, non-adherent patients were more likely to have had SMA-related comorbidities (e.g., feeding difficulties, dyspnea and respiratory anomalies, and muscle weakness) and greater HCRU. Persistence rates 12 months after treatment initiation for patients with SMA types 1, 2, and 3 were 55.2%, 42.4%, and 54.6%, respectively. Patients who discontinued nusinersen and those who did not had generally similar comorbidity profiles. Discontinuation was associated with greater health care costs across SMA types. Conclusion Our analysis of claims data indicated that discontinuation and non-adherence to nusinersen treatment were prevalent, and associated with greater frequency of comorbidities, greater HCRU, and increased costs for patients. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01938-w.

To assess treatment patterns in adults with attention-deficit/hyperactivity disorder (ADHD) and associated healthcare costs in a real-world US setting. Claims data from the IBM MarketScan Commercial Subset (Q1/2014-Q4/2018) was used to identify adults diagnosed with ADHD who newly initiated on ADHD treatment (index date). Treatment sequences were defined using an algorithm; for each sequence, the regimen comprised all ADHD-related agents observed within 30 d of the first agent during the 12-month study period. Treatment changes included discontinuation, switch, add-on, and drop. Treatment characteristics were described for the first treatment regimen observed. Total adjusted annual healthcare costs were compared between patients with no treatment change and patients with 1, 2, and ≥3 treatment changes. Among 122,881 adults with ADHD, the majority initiated a stimulant (95.1%) as their first treatment regimen observed; 9.3% of patients initiated combination therapy of ≥2 ADHD-related agents, and 34.9% of patients had psychotherapy. After an average first treatment regimen duration of 7.1 months, 50.2% of patients experienced a treatment change (22.5% discontinued, 17.5% switched, 5.3% had an add-on, and 4.6% had a treatment drop). Among those who discontinued, 44.8% did so within the first month of initiation. Mean annual healthcare costs were higher among patients with at least 1 treatment change compared to those with no treatment changes; excess costs increased with each additional treatment change. Treatment changes were commonly observed and were associated with excess healthcare cost, emphasizing the unmet treatment needs of adults with ADHD in the US.

Objectives To describe characteristics and compare clinical outcomes including falls, fractures, infections, and neuropsychiatric symptoms (NPS) among long-term care residents with dementia with and without agitation. Methods A cross-sectional secondary analysis of administrative healthcare data was conducted whereby residents with dementia residing in a long-term care facility for ≥12 months were identified from the AnalytiCare LLC database (10/2010-06/2014) and were classified into mutually exclusive cohorts (Agitation Cohort or No-Agitation Cohort) based on available agitation-related symptoms. Entropy balancing was used to balance demographic and clinical characteristics between the two cohorts. The impact of agitation on clinical outcomes was compared between balanced cohorts using weighted logistic regression models. Results The study included 6,265 long-term care residents with dementia among whom, 3,313 were included in the Agitation Cohort and 2,952 in the No-Agitation Cohort. Prior to balancing, residents in the Agitation Cohort had greater dementia-related cognitive impairment and clinical manifestations compared to the No-Agitation Cohort. After balancing, residents with and without agitation, respectively, received a median of five and four distinct types of medications (including antipsychotics). Further, compared to residents without agitation, those with agitation were significantly more likely to have a recorded fall (OR = 1.58), fracture (OR = 1.29), infection (OR = 1.18), and other NPS (OR = 2.11). Conclusions Agitation in long-term care residents with dementia was associated with numerically higher medication use and an increased likelihood of experiencing falls, fractures, infections, and additional NPS compared to residents without agitation, highlighting the unmet need for effective management of agitation symptoms in this population.

Background: Few studies have examined patient characteristics and treatment patterns among patients with dementia and agitation in the United States (US). Objective: To examine real-world treatment patterns and characteristics of patients with agitation related to dementia who were treated with antipsychotics in US residential care and community-based settings. Methods: This retrospective chart review collected US physician-level data from patients 55 to 90 years old initiated on an antipsychotic medication for the treatment of agitation related to dementia from January 2018 to May 2018. Clinical characteristics and treatment patterns were assessed overall and stratified by residential care and community-based settings. Results: A total of 313 participating physicians, 59.5% of whom were primary care physicians, abstracted 801 patient charts (residential care: n = 312; community-based: n = 489). Of patients with agitation who were initiated on an antipsychotic, most patients (74.5%) were initiated within 3 months of the onset of their studied agitation episode, and 62.8% experienced multiple agitation episodes before initiation. While non-pharmacological therapies are recommended first-line approach for agitation in dementia, use of non-pharmacological therapy before initiation of antipsychotics was reported for only 37.8% of patients in residential care and 21.3% in community-based settings. Conclusion: Most patients were initiated on an antipsychotic treatment after multiple episodes of agitation and largely without initial non-pharmacological therapy, suggesting that current treatment guideline recommendations for first-line non-pharmacological intervention may not be adequately followed in clinical practice. Understanding the clinical burden and treatment patterns among dementia patients with agitation is imperative for effective disease management.

Background Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited kidney diseases characterized by progressive development of renal cysts and numerous extra-renal manifestations, eventually leading to kidney failure. Given its chronic and progressive nature, ADPKD is expected to carry a substantial economic burden over the course of the disease. However, there is a paucity of evidence on the impact of ADPKD from a societal perspective. This study aimed to estimate the direct and indirect costs associated with ADPKD in the United States (US). Methods A prevalence-based approach using data from scientific literature, and governmental and non-governmental organizations was employed to estimate direct healthcare costs (i.e., medical services, prescription drugs), direct non-healthcare costs (i.e., research and advocacy, donors/recipients matching for kidney transplants, transportation to/from dialysis centers), and indirect costs (i.e., patient productivity loss from unemployment, reduced work productivity, and premature mortality, caregivers’ productivity loss and healthcare costs). The incremental costs associated with ADPKD were calculated as the difference between costs incurred over a one-year period by individuals with ADPKD and the US population. Sensitivity analyses using different sources and assumptions were performed to assess robustness of estimates and account for variability in published estimates. Results The estimated total annual costs attributed to ADPKD in 2018 ranged from $7.3 to $9.6 billion in sensitivity analyses, equivalent to $51,970 to $68,091 per individual with ADPKD. In the base scenario, direct healthcare costs accounted for $5.7 billion (78.6%) of the total $7.3 billion costs, mostly driven by patients requiring renal replacement therapy ($3.2 billion; 43.3%). Indirect costs accounted for $1.4 billion (19.7%), mostly driven by productivity loss due to unemployment ($784 million; 10.7%) and reduced productivity at work ($390 million; 5.3%). Total excess direct non-healthcare costs were estimated at $125 million (1.7%). Conclusions ADPKD carries a considerable economic burden, predominantly attributed to direct healthcare costs, the majority of which are incurred by public and private healthcare payers. Effective and timely interventions to slow down the progression of ADPKD could substantially reduce the economic burden of ADPKD.

This study synthesized evidence regarding the prevalence of post-traumatic stress disorder (PTSD) in the United States (US).A systematic literature review (SLR) identified recently published (2015-2019) observational studies of PTSD prevalence in the USData from 38 identified articles were categorized by population, diagnostic criteria, and lookback period. Among civilians, point prevalence ranged from 8.0% to 56.7%, 1-year prevalence from 2.3% to 9.1%, and lifetime prevalence from 3.4% to 26.9%. In military populations, point prevalence ranged from 1.2% to 87.5%, 1-year prevalence from 6.7% to 50.2%, and lifetime prevalence from 7.7% to 17.0%. Within these ranges, several estimates were derived from relatively high quality data; these articles are highlighted in the review. Prevalence was elevated in subpopulations including emergency responders, refugees, American Indian/Alaska Natives, individuals with heavy substance use, individuals with a past suicide attempt, trans-masculine individuals, and women with prior military sexual trauma. Female sex, lower income, younger age, and behavioral health conditions were identified as risk factors for PTSD.PTSD prevalence estimates varied widely, partly due to different study designs, populations, and methodologies, and recent nationally representative estimates were lacking. Efforts to increase PTSD screening and improve disease awareness may allow for a better detection and management of PTSD.

International audience; Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.Methods: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.Results: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P

Introduction Infants with spinal muscular atrophy (SMA) type 1 typically face a decline in motor function and a severely shortened life expectancy. Clinical trials for SMA type 1 therapies, onasemnogene abeparvovec (AVXS-101) and nusinersen, demonstrated meaningful improvements in efficacy (e.g., overall survival) but there were no head-to-head clinical trials assessing comparative efficacy. This study estimated the treatment effects of AVXS-101 relative to nusinersen for the treatment of SMA type 1. Methods Overall survival, event-free survival (no death or need to use permanent assisted ventilation), improvement in motor function [increase of ≥ 4 points in Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score from baseline], and motor milestone achievements (head control, rolling over, and sitting unassisted) reported in the onasemnogene abeparvovec (AVXS-101-CL-101; NCT02122952) and nusinersen (ENDEAR; NCT02193074) clinical trials were indirectly compared using frequentist and Bayesian approaches. Results Among symptomatic infants with SMA type 1, the number needed to treat (NNT) to prevent one more death with AVXS-101 instead of nusinersen was 6.2 [95% confidence intervals (CI) = 4.1–12.2], and the probability of preventing death was 20% higher for patients treated with AVXS-101 than nusinersen [risk ratio (RR) = 1.2, 95% CI 1.1–1.3]. For event-free survival, the NNT to prevent one more event was 2.6 (95% CI 2.0–3.6) and RR was 1.6 (95% CI 1.4–1.9). For improvement in motor function, NNT was 3.5 (95% CI 2.6–5.3) and RR was 1.4 (95% CI 1.2–1.6). For milestone achievements, the NNTs were 1.4 (95% CI 1.1–1.9), 1.5 (95% CI 1.1–2.5), and 1.2 (95% CI 1.0–1.5); RRs 4.2 (95% CI 2.6–6.7), 7.8 (95% CI 3.6–17.0), and 11.2 (95% CI 5.1–24.5) for head control, rolling over, and sitting unassisted, respectively. Results were similar using the Bayesian approach. Conclusion This indirect comparison (AVXS-101-CL-101 vs. ENDEAR) among symptomatic SMA type 1 infants suggests that AVXS-101 may have an efficacy advantage relative to nusinersen for overall survival, independence from permanent assisted ventilation, motor function, and motor milestones. Funding AveXis.

Introduction Agitation in individuals with Alzheimer's disease (AD) may predict institutionalization. This study assessed the incremental risk and costs associated with agitation in individuals with AD. Methods A retrospective analysis of the National Alzheimer's Coordinating Center Uniform Data Set (June 2005–February 2018) was conducted. Incremental risk of institutionalization associated with agitation was estimated and used with the number of institutionalized individuals with AD and agitation and costs of living by residential setting in the United States (literature-based), to estimate incremental institutionalization costs. Results The analysis included 11,348 individuals with AD: 6603 (58.2%) with and 4745 (41.8%) without agitation. Compared with individuals without agitation, those with agitation were 20% more likely to be institutionalized (odds ratio = 1.20; 95% CI = 1.08–1.33). Total incremental cost of institutionalization associated with agitation was $4.3 billion ($50,588/individual). Discussion Agitation is associated with a higher risk of institutionalization among patients with AD, which translates into a substantial economic burden., Highlights • Agitation in Alzheimer's disease portends higher risk of institutionalization. • Higher institutionalization risk translates into a substantial economic burden. • Agitation-related institutionalization cost was ∼$4.3 billion in the United States.

To evaluate geographic variation in the prevalence of autosomal dominant polycystic kidney disease (ADPKD) in the US, including ADPKD at risk of rapid progression. Claims data from the IBM MarketScan Commercial and Medicare Supplemental databases (01/16/2016–12/31/2017) were used to estimate the 2017 annual and 2016–2017 two-year prevalence of diagnosed ADPKD and ADPKD at risk of rapid progression in the US overall, and stratified by census regions and states. Risk of rapid progression was identified based on either: hypertension r = .34, one-sided p = .026). In 2017, 37.5% of patients were identified as being at risk for rapid progression, and this proportion was larger among patients in the South (42.1%, p This estimate for ADPKD prevalence is consistent with previously reported national estimates, with regional variation suggesting that ADPKD might be under-diagnosed in rural areas with more limited access to care. More than one-third of ADPKD patients presented risk factors associated with rapid progression, highlighting the need for timely identification, as disease-modifying therapy may delay progression to end-stage renal disease.

To build upon previous outdated studies by comprehensively assessing the direct healthcare burden of autosomal dominant polycystic kidney disease (ADPKD). Patients with ≥2 diagnoses for ADPKD (ADPKD cohort) were identified in the US fee-for-use IBM Truven Health Analytics MarketScan Commercial Claims and Encounters and IBM Truven Health Analytics MarketScan Medicare Supplemental databases (01 January 2015–31 December 2017) and matched (1:3) to controls without ADPKD (non-ADPKD cohort). The index date was the last calendar date followed by 12 months continuous enrollment (study period). Patients with ADPKD were stratified into one of seven mutually exclusive groups based on chronic kidney disease (CKD) stages (I–V), end-stage renal disease requiring renal replacement therapy (ESRD-RRT), and unknown stage. During the 12-month study period, patients with ADPKD incurred significantly higher total healthcare costs than those without ADPKD (mean cost difference = $22,879 per patient per year [PPPY]; p p Results may not be representative of the overall ADPKD US population; CKD stage was based on diagnosis and procedure codes; criteria used to identify ADPKD at risk of rapid progression did not rely on laboratory values; there may be billing inaccuracies and omissions in health insurance claims data. This study demonstrated the substantial healthcare costs associated with ADPKD, which increased as patients progressed through more severe CKD stages.

Introduction:Symptoms of cervical dystonia (CD) can vary in severity and cause significant pain. OnabotulinumtoxinA is an approved treatment for CD. This study assessed health-related quality of life (HRQoL) in patients with CD who received multiple onabotulinumtoxinA treatments.Methods:This prospective, observational standard-of-care study was conducted at multiple neurology centers in Québec, Canada. Patients reported the health impact of CD using the Cervical Dystonia Impact Profile (CDIP)-58, before and after up to eight onabotulinumtoxinA treatments. Other measures included the Cervical Dystonia Severity Rating Scale by physician, employment status using the Work Productivity Questionnaire and pain using the Pain Numeric Rating Scale (PNRS). Adverse events (AEs) were recorded.Results:Sixty-two patients were enrolled (safety population, n = 61; modified efficacy population, n = 58). Participants were mostly females who were employed; most (79.3%) had torticollis. In all, 21/62 patients (33.9%) discontinued the study. At the final visit, there was a statistically significant (p < 0.001) improvement in all eight CDIP-58 subscales, particularly head and neck symptoms (−31.0) and psychosocial functioning (−28.2). Employment increased from baseline (55%) to the end of the study (64%), and there was improvement in work productivity. There was a significant (p < 0.0001) reduction in pain measured by the PNRS, from −0.5 post-treatment 1 to −2.4 at end of study. AEs (neck pain, muscular weakness, dysphagia, nausea) were consistent with onabotulinumtoxinA use.Conclusion:These real-world data indicate that after repeated, long-term use, onabotulinumtoxinA continues to be a safe and effective treatment for CD, improving HRQoL and work productivity.

Psoriasis is a risk factor for cardiovascular events.To assess the risk of major cardiovascular events and the effect of cumulative treatment exposure on cardiovascular event risk in patients with psoriasis treated with tumor necrosis factor-α inhibitors (TNFis) versus phototherapy.Adult patients with psoriasis were selected from a large US administrative claims database (from the first quarter of 2000 through the third quarter of 2014) and classified in 2 mutually exclusive cohorts based on whether they were treated with TNFis or phototherapy. Cardiovascular event risk was compared between cohorts using multivariate Cox proportional hazards models. Cumulative exposure was defined based on treatment persistence.A total of 11,410 TNFi and 12,433 phototherapy patients (psoralen plus ultraviolet A light phototherapy, n = 1117; ultraviolet B light phototherapy, n = 11,316) were included in this study. TNFi patients had a lower risk of cardiovascular events compared to phototherapy patients (adjusted hazard ratio 0.77, P .05). The risk reduction associated with 6 months of cumulative exposure was 11.2% larger for patients treated with TNFis compared to phototherapy (P .05).Information on psoriasis severity and mortality was limited/not available.Patients with psoriasis who were treated with TNFis exhibited a lower cardiovascular event risk than patients treated with phototherapy. Cumulative exposure to TNFis was associated with an incremental cardiovascular risk reduction compared to phototherapy.

Aims: To estimate healthcare resource utilization (HRU) and costs among patients with spinal muscular atrophy (SMA) type 1 (SMA1) in real-world practice, overall and among patients treated with nusinersen. As a secondary objective, HRU and costs were estimated among patients with other SMA types (i.e. 2, 3, or 4 combined), overall and among patients treated with nusinersen. Materials and methods: Patients with SMA were identified from the Symphony Health’s Integrated Dataverse (IDV) open claims database (September 1, 2016–August 31, 2018) and were classified into four cohorts based on SMA type and nusinersen treatment (i.e. SMA1, SMA1 nusinersen, other SMA, and other SMA nusinersen cohorts). The index date was the date of the first SMA diagnosis after December 23, 2016 or, for nusinersen cohorts, the date of nusinersen initiation. The study period spanned from the index date to the earlier among the end of clinical activity or data availability. Results: Patients in the SMA1 (n = 349) and SMA1 nusinersen (n = 45) cohorts experienced an average of 59.4 and 56.6 days with medical visits per-patient-per-year (PPPY), respectively, including 14.1 and 4.6 inpatient days. Excluding nusinersen-related costs, total mean healthcare costs were $137,627 and $92,618 PPPY in the SMA1 and SMA1 nusinersen cohorts, respectively. Mean nusinersen-related costs were $191,909 per-patient-per-month (PPPM) for the first 3 months post-initiation (i.e. loading phase) and $36,882 PPPM thereafter (i.e. maintenance phase). HRU and costs were also substantial among patients in the other SMA (n = 5,728) and other SMA nusinersen (n = 404) cohorts, with an average of 44.5 and 63.7 days with medical visits PPPY and total mean healthcare costs (excluding nusinersen-related costs) of $49,175 and $76,371 PPPY, respectively. Limitations: The database may contain inaccuracies or omissions in diagnoses, procedures, or costs, and does not capture medical services outside of the IDV network. Conclusions: HRU and healthcare costs were substantial in patients with SMA, including in nusinersen-treated patients.

Nephrology nurses face health and wellness challenges due to significant work-related stressors. This survey, conducted online between July 24 and August 17, 2020, assessed the psychological well-being of nephrology nurses in the United States during the COVID-19 pandemic (n = 393). Respondents reported feeling burned out from work (62%), symptoms of anxiety (47% with Generalized Anxiety Disorder-7 [GAD-7] scores ≥ 5), and major depressive episodes (16% with Patient Health Questionnaire-2 [PHQ-2] scores ≥ 3). Fifty-six percent (56%) of survey respondents reported caring for COVID-19 patients, and 62% were somewhat or very worried about COVID-19. Factors, including high workload, age, race, and the COVID-19 pandemic, may partially explain the high proportion of nephrology nurses who reported symptoms of burnout, anxiety, and depression.

Objective The objective of this study was to estimate the US societal economic burden of schizophrenia and update the 2002 reported costs of $62.7 billion given the disease management and health care structural changes of the last decade. Methods A prevalence-based approach was used to assess direct health care costs, direct non-health care costs, and indirect costs associated with schizophrenia (ICD-9 codes 295.xx) for 2013, with cost adjustments where necessary. Direct health care costs were estimated using a retrospective matched cohort design using the Truven Health Analytics MarketScan Commercial Claims and Encounters, Medicare Supplemental, and Medicaid Multistate databases. Direct non-health care costs were estimated for law enforcement, homeless shelters, and research and training. Indirect costs were estimated for productivity loss from unemployment, reduced work productivity among the employed, premature mortality (ie, suicide), and caregiving. Results The economic burden of schizophrenia was estimated at $155.7 billion ($134.4 billion-$174.3 billion based on sensitivity analyses) for 2013 and included excess direct health care costs of $37.7 billion (24%), direct non-health care costs of $9.3 billion (6%), and indirect costs of $117.3 billion (76%) compared to individuals without schizophrenia. The largest components were excess costs associated with unemployment (38%), productivity loss due to caregiving (34%), and direct health care costs (24%). Conclusions Schizophrenia is associated with a significant economic burden where, in addition to direct health care costs, indirect and non-health care costs are strong contributors, suggesting that therapies should aim at improving not only symptom control but also cognition and functional performance, which are associated with substantial non-health care and indirect costs.

Aims: Antipsychotic medications are associated with an increased risk of hyperprolactinemia, but differ in their propensity to cause this complication. This study aimed to assess the economic burden of hyperprolactinemia, and to compare its risk among adult patients using atypical antipsychotics (AAs) with a mechanism of action associated with no/low vs high/moderate prolactin elevation. Methods: This retrospective cohort study was based on US Commercial and Medicaid claims databases. Healthcare costs were compared between matched hyperprolactinemia and hyperprolactinemia-free cohorts using a two-part model. Risk of hyperprolactinemia was compared between patients receiving AAs with a mechanism of action associated with no/low (no/low prolactin elevation cohort) vs high/moderate prolactin elevation (high/moderate prolactin cohort) using logistic regression. Results: In the commercially insured sample, compared to the hyperprolactinemia-free cohort (n = 499), the hyperprolactinemia cohort (n = 499) was associated with incremental total healthcare costs of $5,732 ($20,081 vs $14,349; p = .004), and incremental medical costs of $3,861 ($13,218 vs $9,357; p = .040), mainly driven by hyperprolactinemia-related costs. In the Medicaid-insured sample, compared to the hyperprolactinemia-free cohort, the hyperprolactinemia cohort was associated with incremental total healthcare costs of $10,773 ($30,763 vs $19,990; p = .004), and incremental medical costs of $9,246 ($20,859 vs $11,613; p = .004), mainly driven by hyperprolactinemia-related and mental health-related costs. The odds of hyperprolactinemia in the no/low prolactin elevation cohort were 4–5-times lower than that in the high/moderate prolactin elevation cohort (odds ratio =0.21; p Limitations: Hyperprolactinemia may be under-reported in claims data. Conclusions: Hyperprolactinemia is associated with substantial healthcare costs. AAs associated with no/low prolactin elevation reduce the risk of hyperprolactinemia by 4–5-times compared to AAs associated with moderate/high prolactin elevation. Treatment options with minimal impact on prolactin levels may contribute to reducing hyperprolactinemia burden in AA-treated patients.

Introduction Agitation is among the most common behavioral symptoms of dementia and poses a major challenge for the treatment and management of individuals with dementia. A few studies have shown agitation may be an important predictor of institutionalization; however, these studies were limited to very small sample sizes and focused on behavioral symptoms in general. This study aimed to assess the rate of institutionalization by agitation severity level in patients with dementia. Methods A retrospective cohort analysis was undertaken using the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS), comprising data from 39 past and present Alzheimer's Disease Centers across the United States supported by the National Institute on Aging/National Institute of Health. Eligible individuals had dementia due to Alzheimer's disease, were not institutionalized as of the index date, and had known information on key variables (including residence status) as of the index date and the following annual visit. Agitation severity level was assessed using reported scores per the Neuropsychiatric Inventory Questionnaire (NPI-Q), a behavioral assessment scale. More specifically, agitation was defined per the NPI-Q agitation/aggression scale, where 1=mild (noticeable, but not a significant change), 2= moderate (significant, but not a dramatic change), and 3=severe (very marked or prominent; a dramatic change). Patients with no agitation at any time were included in the “No agitation cohort”. For each patient in the “No agitation cohort”, one visit was randomly selected among all of the patient's visits during which a score on the NPI-Q for the agitation domain was recorded, and the date of the selected visit was defined as the index date. Patients with at least one visit with a score greater than 0 on the agitation domain of the NPI-Q at any time were included in the “Agitation cohort” and classified in the Mild, Moderate, or Severe cohort based on their score on the agitation domain of the NPI-Q as of their index date. For each patient, one visit was randomly selected among all of the patient's visits where a score greater than 0 on the NPI-Q for the agitation domain was recorded, and the date of the selected visit was defined as the index date. Entropy balancing was used to reweight baseline characteristics of individuals included in the “Agitation cohort” and those in the “No agitation cohort” based on age; gender; race; ethnicity; education; primary language; marital status; blood pressure (systolic and diastolic); resting heart rate; active depression; and Clinical Dementia Rating, Geriatric Depression Scale, Modified Hachinski Ischemia Scale, and Functional Activities Questionnaire scores. Institutionalization rates were assessed among balanced cohorts at the first annual visit following the index date. Results A total of 4,344 individuals met the sample selection criteria for the study, of whom 2,798 (64%) were classified as having agitation per the NPI-Q agitation/aggression scale and 1,546 (36%) were in the “No agitation cohort”. Among patients in the balance cohort, 50% were female, 82% were white, and the mean age was 75.2 years ± 9.7. The proportion of patients by agitation severity level at index was 62.2% with mild agitation, 29.5% with moderate agitation, and 8.3% with severe agitation. The risk of transitioning to long-term care over a 12-month period was 4.78% for no agitation, 7.84% for mild agitation, 8.19% for moderate agitation, and 10.13% for severe agitation. Conclusions Study findings support increasing rates of long-term residential placement as agitation progresses which is interlinked with the natural disease progression. To our knowledge, this is one of the few studies reporting rates of institutionalization by agitation severity level, underscoring a need for research and innovation in a prevalent yet underserved condition. This research was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. Lundbeck LLC

Introduction Agitation is among the most common behavioral symptoms of dementia and poses a major challenge for the treatment and management of individuals with dementia. Very few studies report patients’ dependence levels by agitation severity. This study aims to assess the level of care dependency including patients’ functional status. Methods A retrospective cohort analysis was undertaken using the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS), comprising data from 39 past and present Alzheimer's Disease Centers across the United States supported by the National Institute on Aging/National Institute of Health. Eligible individuals had dementia due to Alzheimer's disease and known information on key variables. Agitation severity level was assessed using reported scores per the Neuropsychiatric Inventory Questionnaire (NPI-Q), a behavioral assessment scale. More specifically, agitation was defined per the NPI-Q agitation/aggression scale, where 1=mild (noticeable, but not a significant change), 2= moderate (significant, but not a dramatic change), and 3=severe (very marked or prominent; a dramatic change). Functional status was based on scores reported from the Functional Activities Questionnaire (FAQ) scale ranging 0 to 30, where a score higher than 9 indicates impaired function and possible cognitive impairment. Dependence status was assessed per the question assessing level of dependence and response options included: 1) able to live independently, 2) requires some assistance with complex activities, 3) requires some assistance with basic activities, 4) completely dependent, and 5) unknown. Patients were classified as having agitation if they were reported to have agitation based on the NPI-Q scale for at least one visit. The index date was randomly selected among all visits with agitation, and the severity of agitation was based on the NPI-Q scale as of the index date. For patients without agitation, the index date was randomly selected among all visits. Outcomes were assessed during the 12-month period following the index date (or the next visit if there were no other visits within 12 months). Results A total of 11,346 individuals met the sample selection criteria for the study, of whom 4,745 (42%) were classified as having no agitation per the NPI-Q agitation/aggression scale, 3,861 (34%) with mild agitation, 2,084 (18%) with moderate agitation, and 656 (6%) with severe agitation. The proportion by severity level who reported being “completely dependent” were as follows: 10.2% for no agitation, 21.8% for mild agitation, 29.0% for moderate agitation, and 35.4% for severe agitation. Mean FAQ scores were 14.5 for no agitation, 18.0 for mild agitation, 20.6 for moderate agitation, and 21.9 for severe agitation. Conclusions Study findings show greater dependency and higher functional impairment with progressing agitation. To our knowledge, this is one of the few studies reporting rates of care dependency by agitation severity level, underscoring a need for research and innovation in a prevalent yet underserved condition. This research was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. Lundbeck LLC

To describe real-world treatment patterns of patients receiving colchicine or other treatments during a gout-related emergency room or acute care facility (ER/ACF) visit.An online physician-administered questionnaire was used to collect chart data on 500 patients with a gout-related ER/ACF visit after 16 October 2009; 250 patients receiving colchicine (Colchicine Cohort) and 250 receiving NSAIDs, systemic corticosteroids, narcotics, allopurinol, febuxostat, pegloticase, probenecid, or sulfinpyrazone (Other Cohort). Patient characteristics and treatment received/prescribed during the ER/ACF visit (Period 1 [P1]), at discharge (P2), and at the first follow-up visit (P3) are reported.A total of 45 rheumatologists and 63 primary care physicians participated in the study. Patient mean age was 51 years and 74.8% were male. The most common treatments in the Other Cohort were NSAIDs (59.6%), systemic corticosteroids (45.2%), and narcotics (33.6%). The 500 patients contributed 307 distinct treatment patterns from P1 to P3. Of the 20.6% patients not prescribed a treatment in P2, 60.2% were restarted on a treatment in P3. Of the 78.6% treated patients in P2, 27.0% had a treatment adjustment (dose increase, treatment add-on, or initiation of a different gout-related treatment - not with a urate lowering therapy only) in P3; for 72.6% of these patients, physicians justified the treatment adjustment by inadequacy of the treatment for maintenance therapy, insufficient dosage, or inadequate response. In the Colchicine Cohort, 60.8% of patients were prescribed colchicine consistently from P1 to P3, while 26.8% and 17.7% of patients in the Other Cohort were prescribed consistently NSAIDs and systemic corticosteroids from P1 to P3, respectively.Specific nature of the acute gout-related symptoms or potential attack/flare during the ER/ACF visit was not recorded.Real-world clinical practice reveals a substantial number of distinct treatment patterns and frequent treatment adjustments by treating physicians for patients with a gout-related ER/ACF visit.

Background The current societal costs of bipolar I disorder (BDI) have not been comprehensively characterized in the United States, as previous studies are based on data from two decades ago. Methods The costs of BDI were estimated for 2015 and comprised direct healthcare costs, non-healthcare costs, and indirect costs, calculated based on a BDI prevalence of 1%. The excess costs of BDI were estimated as the difference between the costs incurred by individuals with BDI and those incurred by individuals without BD or individuals from the general population. Direct healthcare costs were assessed using three large US claims databases for insured individuals and the literature for uninsured individuals. Direct non-healthcare and indirect costs were based on the literature and governmental publications. Results The total costs of BDI were estimated at $202.1 billion in 2015, corresponding to an average of $81,559 per individual, while the excess costs of BDI were estimated at $119.8 billion, corresponding to an average of $48,333 per individual. The largest contributors to excess costs were caregiving (36%), direct healthcare costs (21%), and unemployment (20%). In sensitivity analyses, excess costs ranged from $101.2 to $124.3 billion. Limitations Direct healthcare costs were calculated based on a BDI diagnosis, thus excluding undiagnosed patients. Direct non-healthcare and indirect costs were based on combined estimates from the literature. Conclusions Besides direct healthcare costs, BDI was associated with substantial direct non-healthcare and indirect costs. More effective treatments and practices are needed to optimize therapeutic strategies and contain direct and indirect costs.

To compare therapy augmentation and deviation rates from the recommended once-daily dosing regimen in Attention Deficit Hyperactivity Disorder (ADHD) patients initiated on lisdexamfetamine (LDX) vs other once-daily Food and Drug Administration (FDA) approved stimulants.ADHD patients initiated on a long-acting ADHD stimulant medication (index medication) in/after 2007 were selected from a large U.S. administrative claims database. Patients were required to be persistent for ≥90 days and continuously enrolled in their healthcare plan for ≥12 months following treatment initiation date. Based on age and previous treatment status, patients were classified into treatment-naïve children and adolescents (6-17 years old), previously treated children and adolescents, treatment-naïve adults (≥18 years old), and previously treated adults. Furthermore, patients were classified into four mutually exclusive treatment groups, based on index medication: lisdexamfetamine (LDX), osmotic release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate long-acting (MPH LA), and amphetamine/dextroamphetamine long-acting (AMPH LA). The average daily consumption was measured as the quantity of index medication supplied in the 12-month study period divided by the total number of days of supply. Therapy augmentation was defined as the use of another ADHD medication concomitantly with the index medication for ≥28 consecutive days. Therapy augmentation and deviation rates from the recommended once-daily dosing regimen were compared between treatment groups using multivariate logistic regression models.Compared to the other treatment groups, LDX patients were less likely to augment with another ADHD medication (range odds ratios [OR]; 1.28-3.30) and to deviate from the recommended once-daily dosing regimen (range OR; 1.73-4.55), except for previously treated adult patients, where therapy augmentation differences were not statistically significant when compared to OROS MPH and MPH LA patients.This study did not control for ADHD severity.Overall, compared to LDX-treated patients, patients initiated on other ADHD medications were equally or more likely to have a therapy augmentation and more likely to deviate from the recommended once-daily dosing regimen.

Alain Joseph,1 Martin Cloutier,2 Annie Guérin,2 Roy Nitulescu,2 Vanja Sikirica3 1Global HEOR and Epidemiology, Shire, Zählerweg, Zug, Switzerland; 2Analysis Group, Inc., Montreal, Quebec, Canada; 3Global HEOR and Epidemiology, Shire, Wayne, PA, USA Purpose: To compare treatment adherence, discontinuation, add-on, and daily average consumption (DACON) among adults with attention-deficit/hyperactivity disorder receiving second-line lisdexamfetamine dimesylate (LDX) or atomoxetine (ATX), following methylphenidate.Patients and methods: A retrospective cohort study using US commercial claims databases (Q2/2009–Q3/2013).Results: At month 12, the LDX cohort (N=2,718) had a higher adherence level (proportion of days covered: 0.48 versus 0.30, P1 (adjusted odds ratio: 0.20, 95% confidence interval: 0.15–0.25, P

Objective. This study compared the healing of 2 laser ablation units, erbium YAG and femtosecond lasers versus conventional mechanical cutting with carbide and diamond drills to explore future applications for bone surgery. The effects of laser or mechanical ablation combined with rhBMP-7 were also investigated. Methods and materials. Following defect standardization, a full-thickness circular defect was created on the parietal bones of 160 mice divided into 4 groups: carbide drill, diamond drill, erbium YAG laser, and femtosecond laser. Each of the 4 ablation groups was treated with and without BMP 7. Hard tissue healing was assessed using microcomputerized tomography at 3 and 12 weeks postsurgical time points. Results. The femtosecond laser created wounds that showed slightly delayed bone healing during the observation period when compared with mechanical drilling, although the difference was not statistically significant. The Er:YAG laser showed a healing rate similar to that of the mechanically ablated groups. When BMP 7 was added to the surgical sites, bone wound closure occurred at a similar rate in all test groups. Conclusions. The femtosecond and Er:YAG lasers are 2 laser modalities suitable for bone ablation that are comparable to mechanical instrumentation in terms of bone healing. This study suggested that BMP-7 may be used to enhance bone healing with success regardless of the ablative modality used, whether laser or mechanical drilling. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;110:720-728)

Adverse event (AE)-related costs represent an important component of economic models for cancer care. However, since previous studies mostly focused on specific AEs, treatments, or cancer types, limited information is currently available. Therefore, this study assessed the incremental healthcare costs associated with a large number of AEs among patients diagnosed with some of the most prevalent types of cancer. Data were obtained from a large US claims database. Adult patients were included if diagnosed with and treated for one of the following cancer types: breast, digestive organs and peritoneum, genitourinary organs (including bladder and ovary and other uterine adnexa), lung, lymphatic and hematopoietic tissue, and skin. Treatment episodes were defined as the period from initiation of the first antineoplastic pharmacologic therapy to discontinuation (i.e., gap of ≥ 45 days), or change in treatment regimen, or end of data availability. A total of 36 AEs were selected from the product inserts of 104 treatments recommended by practice guidelines. A retrospective matched cohort design was used, matching a treatment episode with a certain AE with a treatment episode without that AE. A total of 412,005 patients were selected, for a total of 794,243 treatment episodes, resulting in 1,617,368 matched treatment episodes across all 36 AEs. Incremental healthcare costs associated with AEs of any severity ranged from $546 for cough/upper respiratory infections to $24,633 for gastrointestinal perforation. The three most costly AEs when considering any severity were gastrointestinal perforation ($24,633), central nervous system hemorrhage ($24,322), and sepsis/septicemia ($23,510). Incremental healthcare costs associated with severe AEs ranged from $15,709 for dermatitis and rash to $48,538 for gastrointestinal fistula. The three most costly severe AEs were gastrointestinal fistula ($48,538), gastrointestinal perforation ($41,281), and central nervous system hemorrhage ($38,428). In conclusion, AEs during treatment episodes for cancer were frequent and associated with a substantial economic burden.

The existing literature suggests the Bayesian-Frequentist debate could soon be involved in the prioritization of hits from HTS campaigns. The Bayesian-Frequentist debate reflects two archetypical attitudes regarding the process of conducting scientific and technological research. This review article covers recent advances in statistical analyses, currently in use, for hit selection in the drug discovery process. The impact of decisions (e.g. attrition) executed at early stages in the drug discovery process influences HTS performance in later development stages. It shows that, as the high content value of the information from HTS campaigns increases over time, the two statistical approaches aim to provide similar answers, but they might not succeed.

Paraoxonase1 is a HDL-associated enzyme, which is responsible for their antioxidant property. This study was aimed to investigate the effect of PON1 [Q192R] and [L55M] genotypes on susceptibility of LDL and HDL to lipid peroxidation and on antioxidant activity of HDL as a function of aging. Seventy-eight healthy subjects distributed in two age groups, young (20–30 years) and elderly (60–89 years) were recruited. PON1 activities and genotype polymorphisms were determined for each subject. LDL and HDL susceptibility to lipid peroxidation was evaluated by the measure of lag-phase (LP) for conjugated diene formation. HDL antioxidant property was evaluated by the measure of their capacity to protect LDL against lipid peroxidation. Our results show that LP for LDL and HDL peroxidation decreased with age of donors. Moreover, PON1 genotypes affect significantly the susceptibility of LDL and HDL to lipid peroxidation. Furthermore, basal- and salt-stimulated paraoxonase as well arylesterase activities were significantly reduced in elderly compared to young subjects. These results show a beneficial effect of PON1 towards susceptibility of HDL to oxidation as well to their antioxidant effect. However, this PON1 protective effect seems to be blunted with advancing age. Altogether our results suggest that the decrease in the PON1 protective effect with aging may contribute to the acceleration of the atherosclerosis process in elderly.

Our aim in this study was to investigate the effect of aging on the capacity of HDLs to promote reverse cholesterol transport. HDLs were isolated from plasma of young (Y-HDL) and elderly (E-HDL) subjects. HDL-mediated cholesterol efflux was studied using THP-1 and J774 macrophages. Our results show that E-HDLs present a lower capacity to promote cholesterol efflux than Y-HDLs (41.7 +/- 1.4% vs. 49.0 +/- 2.2%, respectively; P = 0.013). Reduction in the HDL-mediated cholesterol efflux capacity with aging was more significant with HDL(3) than HDL(2) (Y-HDL(3), 57.3 +/- 1% vs. E-HDL(3), 50.9 +/- 2%; P = 0.012). Moreover, our results show that ABCA1-mediated cholesterol efflux is the more affected pathway in terms of cholesterol-removing capacity. Interestingly, the composition and structure of HDL revealed a reduction in the phosphatidylcholine-sphingomyelin ratio (E-HDL, 32.7 +/- 2.7 vs. Y-HDL, 40.0 +/- 1.9; P = 0.029) and in the phospholipidic layer membrane fluidity in E-HDL compared with Y-HDL as well as an alteration in the apolipoprotein A-I structure and charge. In conclusion, our results shown that E-HDLs present a reduced capacity to promote cholesterol efflux, principally through the ABCA1 pathway, and this may explain the increase of the incidence of cardiovascular diseases observed during aging.

Oxidative modification of low-density lipoprotein (LDL) particles has been implicated in the process of atherogenesis. Antioxidants that prevent LDL from oxidation may reduce atherosclerosis. We have investigated the protective effect of Peganum harmala-extract (P-extract) and the two major alkaloids (harmine and harmaline) from the seeds of P. harmala against CuSO4-induced LDL oxidation. Through determination of the formation of malondialdehyde (MDA) and conjugated diene as well as the lag phase, the extract (P-extract) and compounds were found to possess an inhibitory effect. Moreover, harmaline and harmine reduced the rate of vitamin E disappearance and exhibited a significant free radical scavenging capacity (DPPH•). However, harmaline had a markedly higher antioxidant capacity than harmine in scavenging or preventive capacity against free radicals as well as inhibiting the aggregation of the LDL protein moiety (apolipoprotein B) induced by oxidation. The results suggested that P. harmala compounds could be a major source of compounds that inhibit LDL oxidative modification induced by copper.

The aim of this study was to delineate the mode of action of 20-hydroxy-eicosatetraenoic acid (20-HETE) in airway smooth muscle (ASM) cells. ASM metabolizes arachidonic acid by various enzymatic pathways, including the cytochrome P-450 (CYP-450) ω-hydroxylase, which leads to the production of 20-HETE, a bronchoconstrictive eicosanoid. The present study demonstrated that 20-HETE induced concentration-dependent tonic responses in ASM, whereas transient responses were recorded in Ca2+-free solution, suggesting an intracellular Ca2+release process. 20-HETE inotropic responses were abolished by 36 μM 2-aminoethoxydiphenyl borate or 1 μM thapsigargin but were insensitive to 10 μM ryanodine, indicating that inositol triphosphate receptors likely control the release of intracellular Ca2+. Sustained tension, which required Ca2+entry, was partially blocked by 1 μM nifedipine (an L-type) and 100 μM Gd3+(a nonselective cationic channel blocker). Moreover, in the absence of selective 20-HETE receptor antagonists, 20-HETE tonic responses were inhibited in a concentration-dependent manner (0.1–10 μM) by capsazepine, a well-characterized vanilloid receptor antagonist. Capsazepine was also observed to reverse cumulative responses to 20-HETE and capsaicin, a TRPV1 agonist. In addition, capsazepine pretreatment largely modified the sustained inotropic responses to 20-HETE, suggesting that 20-HETE cross-reacted with TRPV1 receptors with a low affinity (μM) or that its specific receptor was inhibited by the vanilloid antagonist. Data obtained using RHC-80267, ONO-RS-082, and eicosatetraynoic acid, respective inhibitors of diacylglycerol-lipase, phospholipase A2, and CYP-450 ω-hydroxylase, reveal that intracellular arachidonic acid production and its 20-HETE metabolite may be responsible for the activation of nonselective cationic channels and tonic responses.

20-Hydroxyeicosatetraenoic acid (20-HETE) controls several mechanisms such as vasoactivity, mitogenicity, and ion transport in various tissues. Our goal was to quantify the effects of 20-HETE on the electrophysiological properties of airway smooth muscle (ASM). Isometric tension measurements, performed on guinea pig ASM, showed that 20-HETE induced a dose-dependent inotropic effect with an EC50 value of 1.5 μM. This inotropic response was insensitive to GF-109203X, a PKC inhibitor. The sustained contraction, requiring Ca2+ entry, was partially blocked by either 100 μM Gd3+ or 1 μM nifedipine, revealing the involvement of noncapacitative Ca2+ entry and L-type Ca2+ channels, respectively. Microelectrode measurements showed that 3 μM 20-HETE depolarized the membrane potential in guinea pig ASM by 13 ± 2mV( n = 7), as did 30 μM 1-oleoyl-2-acetyl- sn-glycerol. Depolarizing effects were also observed in the absence of epithelium. Patch-clamp recordings demonstrated that 1 μM 20-HETE activated a nonselective cationic inward current that may be supported by the activation of transient receptor potential channels. The presence of canonical transient receptor potential mRNA was confirmed by RT-PCR in guinea pig ASM cells.

To compare treatment persistence in attention-deficit/hyperactivity disorder (ADHD) of patients initiated on lisdexamfetamine (LDX) vs other ADHD medications.A large US administrative claims database was used to select ADHD patients who initiated an ADHD medication (index treatment) during/after 2007. Patients were classified, based on age and previous treatment status, as treatment-naïve or previously treated children and adolescents (6-17 years) and treatment-naïve or previously treated adults (18 years and older). Furthermore, patients were classified into seven mutually exclusive treatment groups, based on their index treatment: LDX, atomoxetine (ATX), osmotic-release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate short-acting (MPH SA) and long-acting (MPH LA), and amphetamine/dextroamphetamine short acting (AMPH SA) and long-acting (AMPH LA). Treatment persistence, analyzed through discontinuation (interruption of the index treatment for ≥30 consecutive days), was compared between treatment groups using multivariate Cox proportional hazards. Patients were followed until first treatment discontinuation or up to 12 months after the initiation of the index treatment, whichever occurred first.Among children and adolescents, LDX patients had a significantly lower discontinuation rate compared to other treatment groups (range hazard ratios [HRs]; 1.04-2.26; all p 0.05), except when compared to treatment-naïve patients on ATX and OROS MPH, where no statistically significant differences were found and where LDX had a higher risk of discontinuation, respectively. Among adults, LDX patients had a significantly lower discontinuation rate compared to patients in other treatment groups (range HR; 1.14-1.86; all p 0.05), except for the comparison with AMPH LA patients, where differences were not statistically significant.This study did not control for ADHD severity.LDX-treated patients were associated with higher persistence compared to patients initiated on other ADHD medications, except for the comparisons with OROS MPH and ATX treated patients in treatment-naïve children and adolescents and AMPH LA-treated patients in adults.

To assess treatment adherence in attention deficit/hyperactivity disorder (ADHD) patients initiated on Lisdexamfetamine (LDX) vs other FDA-approved stimulants and non-stimulant medications.ADHD patients initiated on an ADHD medication (index medication) were selected from a large US administrative claims database. Based on age and previous treatment status, patients were classified into treatment-naïve children and adolescents (6-17 years old), previously treated children and adolescents, treatment-naïve adults (over 18 years old), and previously treated adults. Furthermore, based on their index medication, patients were classified into seven mutually exclusive treatment groups: LDX, atomoxetine (ATX), osmotic release methylphenidate hydrochloride long acting (OROS MPH), other methylphenidate/dexmethylphenidate long acting (MPH LA) and short acting (MPH SA), and amphetamine/dextroamphetamine short acting (AMPH SA) and long acting (AMPH LA). Treatment adherence (proportion of days covered by the index medication ≥0.8) over a 12-month period was compared across treatment groups using multivariate logistic regression models.In children and adolescents, LDX patients were more likely to be adherent compared to patients in each of the other treatment groups, except in treatment-naïve patients where LDX patients had a similar likelihood (p = 0.6925) and were less likely (p = 0.0004) to be adherent compared to ATX and OROS MPH patients, respectively. In adults, the LDX treatment group was also more likely to be adherent compared to each of the other treatment groups, except compared to AMPH LA, where statistically insignificant differences were observed (previously treated: p = 0.6471, treatment-naïve: p = 0.0733).ADHD severity information was not available in the database. Accordingly, this study did not control for ADHD severity.Overall, LDX-treated patients demonstrated a better treatment adherence compared to patients initiated on other ADHD medications, except for AMPH LA in adult and OROS MPH and ATX in treatment-naïve children and adolescents.

e20549Background: A Phase 2 clinical trial of veliparib + carboplatin (C) and paclitaxel (P) in patients (pts) with previously untreated metastatic/advanced NSCLC showed that veliparib may improve ...

Patients treated with epidermal growth factor receptor inhibitors (EGFRIs) may develop dermatologic adverse drug reactions (ADRs) that may affect patients' quality-of-life, require medical care, and may lead to substantial costs. This study assessed the economic burden of dermatologic ADRs in colorectal cancer (CRC), head and neck cancer (HNC), and non-small cell lung cancer (NSCLC) patients.Adult patients with ≥1 diagnosis for the study cancer initiated on EGFRIs indicated for CRC, HNC, and NSCLC were selected from a large commercial database (MarketScan Commercial Database [2000-2010]; Thomas Reuters, New York, NY). For each cancer type, patients were classified into two mutually exclusive cohorts: 'ADR' (patients with ≥1 ADR following EGFRI initiation) and 'ADR-free' (patients without any ADR). Patients were observed from the index date up to the end of continuous healthcare plan enrollment or 90 days after EGFRI discontinuation, whichever occurred first. For each cancer group, the proportion of patients and the incidence rate (IR) of experiencing ≥1 dermatologic ADR were reported. Incidence rate ratios for healthcare resource utilization and monthly incremental costs (2010 USD) were estimated using Poisson regression and generalized linear or two-part models, respectively.Overall, the proportion of patients with ≥1 ADR ranged between 20.5-36.4% across cancer groups (IR ranged between 44.2-57.4 per 100 patient-years). After adjusting for confounders, in each cancer group, ADR patients had higher incidence of healthcare resource utilization, generally driven by higher incidence of emergency room visits and incurred incremental total monthly healthcare costs that ranged between $2284-$3210 across cancer groups.There was no clinical measure of cancer staging and ADR severity in the database.Results suggest that patients with CRC, NSCLC, and HNC, who may benefit from EGFRI therapies, may also incur a substantial economic burden that is associated with dermatologic ADRs.

Background This retrospective cohort study compared rates of treatment persistence, incidences of de novo stroke, arterial embolism, and hemorrhage/bleeding, and healthcare resource use and costs between atrial fibrillation/flutter (AF/AFL) patients receiving concomitant warfarin (W)+amiodarone (A) or warfarin+other antiarrhythmic drug (OAAD) therapy in real-world practice. Methods The Ingenix IMPACT database (1997–2009) was used to identify patients with ≥1 diagnostic claim for AF/AFL and concurrent pharmacy claims (≥60days' supply) for W and A ( n =4238) or W+OAAD ( n =6332) within the first 90days of initiating therapy. Outcomes of interest were assessed over 12months following initiation of dual therapy. Results The W+A cohort was older than the W+OAAD cohort (mean 66.5 vs. 61.9years) and had greater baseline comorbidity. The W+A cohort had significantly 1) lower rates of treatment persistence; 2) higher incidences of de novo stroke (hazard ratio [HR] 1.24), arterial embolism (HR 1.48) and combined stroke/hemorrhage/bleeding/arterial embolism (HR 1.25); 3) more frequent inpatient (incidence rate ratio [IRR] 1.25), emergency room (IRR 1.16) and outpatient (IRR 1.07) admissions; and 4) higher incidences of cardiovascular- (IRR 1.35) and arterial embolism- (IRR 1.94) related healthcare use than the W+OAAD cohort. Incremental total healthcare costs over 12months were $4114 ($2397 inpatient; $1171 outpatient). Conclusions Allowing for differences in prescribing practice, AF/AFL patients treated with W+A are at higher risk of stroke and arterial embolism, and have higher healthcare use and costs, than patients receiving W+OAAD.

Femtosecond (fs) ablation is mediated via electron avalanche and multiphoton ionization and is characterized by very precise cutting and undetectable thermal damage in biological tissues. We have used a 775nm, 150 fs, 1kHz laser system compared to two conventional bone cutting techniques using carbide and diamond tip burs in a mice calvarial wound healing model. Wound healing was evaluated using micro computerized tomographs and histological techniques. Good healing outcomes were found for fs laser surgery in comparison to the conventional surgical methods. However, the degree of healing was highly variable in all treatment groups. The realization of healing comparable to that observed for conventional surgical tools demonstrates the possible use of fs lasers for clinical surgery involving small bones where a much higher degree of precision is required than that possible with current methods.

This report discusses the management of a 21-year-old male who developed a peripheral giant cell granuloma (PGCG) associated with dental implant therapy, and reviews 4 previously reported cases of PGCGs developing in association with dental implant treatment. The patient described in this report was treated with multiple dental implants to manage severe oligodontia. Six years after implant placement, with the patient lost to follow-up, he presented to his dentist complaining of increasing swelling in the right mandibular vestibule. The patient was noted to have a large exophytic, ovoid-shaped, firm, smooth-surfaced, maroon-colored lesion. The lesion was found to be a PGCG associated with a dental implant. The lesion was treated successfully by explantation of the dental implant, complete excision of the lesion, and curettage of the underlying bony defect. No evidence of recurrence was seen over 12 months of follow-up.