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Grasslands are the largest contributor of nitrous oxide (N2O) emissions in the agriculture sector due to livestock excreta and nitrogen fertilizers applied to the soil. Nitrification inhibitors (NIs) added to N input have reduced N2O emissions, but can show a range of efficiencies depending on climate, soil, and management conditions. A meta-analysis study was conducted to investigate the factors that influence the efficiency of NIs added to fertilizer and excreta in reducing N2O emissions, focused on grazing systems. Data from peer-reviewed studies comprising 2164 N2O emission factors (EFs) of N inputs with and without NIs addition were compared. The N2O EFs varied according to N source (0.0001–8.25%). Overall, NIs reduced the N2O EF from N addition by 56.6% (51.1–61.5%), with no difference between NI types (Dicyandiamide—DCD; 3,4-Dimethylpyrazole phosphate—DMPP; and Nitrapyrin) or N source (urine, dung, slurry, and fertilizer). The NIs were more efficient in situations of high N2O emissions compared with low; the reduction was 66.0% when EF > 1.5% of N applied compared with 51.9% when EF ≤ 0.5%. DCD was more efficient when applied at rates > 10 kg ha−1. NIs were less efficient in urine with lower N content (≤ 7 g kg−1). NI efficiency was negatively correlated with soil bulk density, and positively correlated with soil moisture and temperature. Better understanding and management of NIs can optimize N2O mitigation in grazing systems, e.g., by mapping N2O risk and applying NI at variable rate, contributing to improved livestock sustainability.

This study assessed the healthcare resource utilization (HRU) and cost burden of patients with major depressive disorder (MDD) and acute suicidal ideation or behavior (SIB; MDSI) versus those with MDD without SIB and those without MDD.Adults were selected from the MarketScan® Databases (10/2015-02/2020). The MDSI cohort received an MDD diagnosis within 6 months of a claim for acute SIB (index date). The index date was a random MDD claim in the MDD without SIB cohort and a random date in the non-MDD cohort. Patients had continuous eligibility ≥12 months pre- and ≥1 month post-index. HRU and costs were compared during 1- and 12-month post-index periods between MDSI and control cohorts matched 1:1 on demographics.The MDSI cohort included 73,242 patients (mean age 35 years, 60.6% female, 37.2% Medicaid coverage). At 1 month post-index, the MDSI cohort versus the MDD without SIB/non-MDD cohorts had 12.8/67.2 times more inpatient admissions and 3.3/8.9 times more emergency department visits; they had 2.9 times more outpatient visits versus the non-MDD cohort (all p 0.001). The MDSI cohort had incremental mean healthcare costs of $5255 and $6674 per-patient-month versus the MDD without SIB and non-MDD cohorts (all p 0.001); inpatient costs drove up to 89.5% of incremental costs. At 12 months post-index, HRU and costs remained higher in MDSI versus control cohorts.SIB are underreported in claims; unobserved confounders may cause bias.MDSI is associated with substantial excess healthcare costs driven by inpatient costs, concentrated in the first month post-index, and persisting during the following year.

Introduction Pre-existing conditions relevant for adverse events (AE) and the potential for drug–drug interactions (DDIs) may limit safe pharmacotherapeutic augmentation options for patients with major depressive disorder (MDD). This concern may be heightened among patients with treatment-resistant depression (TRD), who often have comorbid medical disorders. Methods Adults with MDD and ≥ 1 antidepressant claim within the first observed major depressive episode were identified in the MarketScan® Databases. Those initiating a new regimen after two regimens at adequate dose and duration were considered to have TRD. The index date was defined at TRD onset or on a random antidepressant claim among patients with non-TRD MDD. Pre-existing conditions 12 months pre-index and potential DDIs 3 months pre/post-index associated with specific non-antidepressant augmentation therapies, including atypical antipsychotics (APs), buspirone, psychostimulants, anticonvulsants, thyroid hormone, and lithium were compared between 1:1 matched TRD and non-TRD MDD cohorts. Results Overall, 3414 patients with TRD and non-TRD MDD (mean age 39.7 years, 69% female) were matched. Relative to non-TRD MDD, patients with TRD had 33% higher likelihood of ≥ 1 pre-existing condition relevant for AEs listed in product labels of non-antidepressant augmentation therapies (p

Aim: Estimate the cost-per-remitter with esketamine nasal spray plus an oral antidepressant (ESK + oral AD) versus oral AD plus nasal placebo (oral AD + PBO) among patients with treatment-resistant depression. Patients & methods: An Excel-based model was developed to estimate the cost-per-remitter for ESK + oral AD versus oral AD + PBO over 52 weeks from multiple US payer perspectives. Clinical end points and cost inputs were derived from clinical trials and the literature, respectively. Results: Under the base-case scenario, the cost-per-remitter for ESK + oral AD and oral AD + PBO were as follows: Commercial: US$85,808 versus US$100,198; Medicaid: US$76,236 versus US$96,067; Veteran’s Affairs: US$77,765 versus US$104,519; and Integrated Delivery Network: US$103,924 versus US$142,766. Conclusion: The findings suggest that ESK + oral AD is a cost-efficient alternative treatment for treatment-resistant depression compared with oral AD + PBO.

To compare health care resource utilization (HCRU), short-term disability days, and costs between states of persistence on antidepressant lines of therapy after evidence of treatment-resistant depression (TRD). Patients with major depressive disorder (MDD) were identified in the IBM MarketScan Commercial and Medicare Supplemental Databases (01/01/2013���03/04/2019), Multi-State Medicaid Database (01/01/2013���12/31/2018), and Health Productivity Management Database (01/01/2015���12/31/2018). The index date was the date of the first evidence of TRD during the first observed major depressive episode. The follow-up period was divided into 45-day increments and categorized into persistence states: (1) evaluation (first 45 days after evidence of TRD); (2) persistence on the early line after evidence of TRD; (3) persistence on a late line; and (4) non-persistence. HCRU, short-term disability days, and costs were compared between persistence states using multivariate generalized estimating equations. Among 10,053 patients with TRD, the evaluation state was associated with higher likelihood of all-cause inpatient admissions (odds ratio [OR; 95% confidence interval (CI)] = 1.79 [1.49, 2.14]), emergency department visits (OR [95% CI] = 1.23 [1.12, 1.34]), and outpatient visits (OR [95% CI] = 3.83 [3.51, 4.18]; all p p p p = .028) relative to the early line. Medication may have been dispensed but not actually taken. Higher costs during the first 45 days after evidence of the presence of TRD and during persistence on a late line relative to persistence on the early-line therapy suggest there are benefits to using more effective treatments earlier.

Objective:This study compared health care use and costs among patients with treatment-resistant versus treatment-responsive depression across Medicaid, Medicare, and commercial payers.Methods:A ret...

To compare the clinical and economic burden of treatment-resistant depression (TRD) among older adult patients with major depressive disorder (MDD) to non-TRD MDD and non-MDD patients.Retrospective cohort study using 5% Medicare data (January 1, 2012-December 31, 2015) for MDD patients aged ≥65 years who were defined as TRD if they received ≥2 antidepressant treatments in the current episode. MDD patients not meeting TRD criteria were deemed non-TRD MDD; those without an MDD diagnosis were categorized as non-MDD. All were required to have continuous health plan enrollment for ≥6 months pre- and ≥12 months postindex date (index: first antidepressant claim/random [non-MDD]). Three cohorts were matched, and generalized linear and Cox proportional hazards models were used to compare medication use, healthcare resource utilization, costs, and risks of initial hospitalization and readmission ≤30 days postdischarge from initial hospitalization.After matching, 178 patients from each cohort were analyzed. During 12 months of follow-up, TRD patients had higher use of different antidepressants and antipsychotics, higher inpatient and emergency room visits, longer inpatient stays, and higher total healthcare costs ($24,543 versus $16,059, $8,058) than non-TRD MDD and non-MDD cohorts, respectively (all p0.05). Risk of initial hospitalization was higher in the TRD (hazard ratio [HR] = 3.60, 95% confidence interval [CI] = 2.08-6.23) and non-TRD MDD cohorts (HR = 1.82, 95% CI = 1.02-3.25) than the non-MDD cohort.The burden of MDD among older adult Medicare beneficiaries is substantial, and even greater among those with TRD compared to non-TRD MDD, demonstrating the need for more effective treatments than those currently available.

Objective: To assess the real-world use of home health services (HHS) among patients with major depressive disorder (MDD) with and without treatment-resistant depression (TRD).Methods: Adults (18–6...

Background: Esketamine nasal spray plus an oral antidepressant is approved in adults with major depressive disorder with acute suicidal ideation or behavior (MDSI). Methods: A budget impact analysis from a US payer perspective was performed with a hypothetical 1-million-member plan, using pharmacy and medical costs associated with adding esketamine plus an oral antidepressant to usual care. Results: Estimated annual total healthcare costs of managing patients with MDSI increased from $32,988,247 without esketamine to $34,161,188 in Year 3 with esketamine (primarily due to medical costs). The per-member-per-month incremental costs were $0.02, $0.06 and $0.10 in Years 1, 2 and 3, respectively. Conclusion: Incorporation of esketamine results in a modest estimated impact on the annual budget over a 3-year time horizon.

To ascertain the relative importance of attributes considered when deciding to discharge patients hospitalized with major depressive disorder (MDD) and active suicidal ideation with intent, a choice-based conjoint analysis was conducted via online survey among US-based psychiatrists actively managing such patients. Potential attributes and attribute levels were identified. Attribute importance in decision to discharge and the discharge time frame were assessed. One hundred psychiatrists completed the survey. The relative importance of attributes were current MDD severity (relative importance weight [out of 100] 24.8 [95% confidence interval, 23.3-26.3]), clinician assessment of current suicidal ideation (20.8 [18.5-23.0]), previous history of suicide attempts (16.7 [15.9-17.6]), psychosocial support at discharge (13.0 [11.7-14.4]), postdischarge outpatient follow-up (9.8 [8.8-10.8]), current length of hospital stay (9.2 [8.1-10.3]), and suicidal ideation at admission (5.7 [4.8-6.6]). Thus, current clinical symptoms were considered the most important attributes by psychiatrists when discharging patients initially hospitalized with MDD and active suicidal ideation with intent.

Objective: To examine the incremental mental health care resource utilization (MHRU) and barriers to receiving mental health services among adults with a major depressive episode (MDE) and suicidal ideation or behavior with intent. Methods: Data from adult participants in the 2017 National Survey on Drug Use and Health were used to identify 3 cohorts: MDE (determined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5] criteria) with suicidal ideation or behavior with intent (MDSI), MDE, and non-MDE. MHRU and barriers to receiving mental health services were compared among cohorts using logistic regression models. Results: The MDSI cohort had significantly higher odds (adjusted odds ratio [95% confidence interval]) of receiving mental health-related inpatient care, outpatient care, prescription medications, and any treatment versus the MDE cohort (10.2 [7.1-14.6], 2.4 [1.7-3.4], 2.4 [1.8-3.3], and 2.6 [1.8-3.7], respectively) and the non-MDE cohort (40.3 [27.3-59.5], 20.0 [14.5-27.7], 17.2 [12.9-22.9], and 19.6 [14.1-27.1], respectively). Compared to the MDE cohort, the MDSI cohort was significantly more likely to report barriers to receiving mental health services (2.6 [2.0-3.4]), with the largest differences between cohorts related to fear of negative impact (3.9 [2.8-5.4]). Additionally, 30.6% of the MDSI cohort and 47.0% of the MDE cohort did not receive any mental health treatment in the past year. Conclusions: Although respondents in the MDSI cohort reported substantially higher MHRU across all categories, they also reported greater barriers to receiving care than those in the MDE cohort. This study documents the extensive burden and unmet need in the MDSI population.

Objective: To compare direct and indirect costs among caregivers of patients with major depressive disorder (MDD) and suicidal ideation and/or suicide attempts (MDSI) versus caregivers of patients with MDD alone versus caregivers of patients without MDD or suicidal ideation and/or suicide attempts (controls). Methods: Cohorts were based on caregivers of adult patients with MDSI, MDD alone, and controls. Patients were identified by Workpartners employer database ICD-9/ICD-10 codes (January 2010 to July 2019) and were spouses or domestic partners of employees (caregivers). Twenty controls and 20 MDD-alone caregivers were matched to each MDSI caregiver on sex, age, and index year. All caregiver-patient pairs had 6 months pre/postindex information and met additional inclusion/exclusion criteria. Patient and caregiver medical and prescription claims and caregiver absenteeism (payment/time) were analyzed. Direct costs (medical, prescription) and indirect costs (absence payments by benefit type) were analyzed using separate, 2-part stepwise regression models and controlling for demographics, job-related variables, region, index year, and Charlson Comorbidity Index score. Results: 570 MDSI caregiver-patient pairs and 11,400 matched MDD-alone and control pairs were identified. MDSI and MDD-alone caregivers had higher medical costs compared with controls ($5,131 and $4,548 versus $3,885, respectively; P

Aim: To evaluate Medicaid spending and healthcare resource utilization (HRU) in treatment-resistant depression (TRD). Materials & methods: TRD beneficiaries were identified from Medicaid claims databases (January 2010–March 2017) and matched 1:1 with major depressive disorder (MDD) beneficiaries without TRD (non-TRD-MDD) and randomly selected patients without MDD (non-MDD). Differences in HRU and per-patient-per-year costs were reported in incidence rate ratios (IRRs) and cost differences (CDs), respectively. Results: TRD beneficiaries had higher HRU than 1:1 matched non-TRD-MDD (e.g., inpatient visits: IRR = 1.41) and non-MDD beneficiaries (N = 14,710 per cohort; e.g., inpatient visits: IRR = 3.42, p Conclusion: TRD is associated with higher HRU and costs versus non-TRD-MDD and non-MDD. TRD poses a significant burden to Medicaid.

Objective Estimates of prevalence and burden of treatment-resistant depression (TRD) vary widely in the literature. This study evaluated the prevalence and burden of TRD and the share of TRD in the burden of medication-treated major depressive disorder (MDD) using the most commonly accepted definition of TRD and a novel bottom-up approach. Methods Prevalence and health care burden of TRD were estimated by synthetizing inputs across 4 similarly designed claims studies in adults covered by Medicare, Medicaid, commercial plans, and the US Veterans Health Administration (VHA). Productivity (absenteeism and presenteeism) and unemployment burden were estimated based on inputs from a study conducted with data from the Kantar National Health and Wellness Survey (NHWS; 2017). A targeted literature search for additional inputs was performed. A cost model was developed to estimate the burden of TRD and medication-treated DSM-5-defined MDD in the United States. Study outcomes were the 12-month prevalence of TRD and the annual health care, productivity, and unemployment burden of TRD and medication-treated MDD in the United States. Results The estimated 12-month prevalence of medication-treated MDD in the United States was 8.9 million adults, and 2.8 million (30.9%) had TRD. The total annual burden of medication-treated MDD among the US population was $92.7 billion, with $43.8 billion (47.2%) attributable to TRD. The share of TRD was 56.6% ($25.8 billion) of the health care burden, 47.7% ($8.7 billion) of the unemployment burden, and 32.2% ($9.3 billion) of the productivity burden of medication-treated MDD. Conclusions TRD is associated with disproportionate health care costs and unemployment, suggesting potentially large economic and societal gains with effective management.

Objectives To create and validate a model to predict depression symptom severity among patients with treatment‐resistant depression (TRD) using commonly recorded variables within medical claims databases. Methods Adults with TRD (here defined as > 2 antidepressant treatments in an episode, suggestive of nonresponse) and ≥ 1 Patient Health Questionnaire (PHQ)‐9 record on or after the index TRD date were identified (2013–2018) in Decision Resource Group's Real World Data Repository, which links an electronic health record database to a medical claims database. A total of 116 clinical/demographic variables were utilized as predictors of the study outcome of depression symptom severity, which was measured by PHQ‐9 total score category (score: 0–9 = none to mild, 10–14 = moderate, 15–27 = moderately severe to severe). A random forest approach was applied to develop and validate the predictive model. Results Among 5,356 PHQ‐9 scores in the study population, the mean (standard deviation) PHQ‐9 score was 10.1 (7.2). The model yielded an accuracy of 62.7%. For each predicted depression symptom severity category, the mean observed scores (8.0, 12.2, and 16.2) fell within the appropriate range. Conclusions While there is room for improvement in its accuracy, the use of a machine learning tool that predicts depression symptom severity of patients with TRD can potentially have wide population‐level applications. Healthcare systems and payers can build upon this groundwork and use the variables identified and the predictive modeling approach to create an algorithm specific to their population., In this study, we created and validated a machine learning model using commonly recorded variables within a medical claims database to predict depression symptom severity of patients with TRD based on Patient Health Questionnaire (PHQ)‐9 scores available within an electronic health record (EHR) database. The model was found to predict depression symptom severity category from the three possible severity category choices with an overall accuracy of 62.7%. Of the 116 clinical and demographic variables evaluated in our study, six were found to be the most important predictors. To our knowledge, this is the first study which attempts to predict depression symptom severity of patients with TRD using clinical and demographic characteristics in a medical claims database.

Objective To use the Clinical Global Impression‐Severity (CGI‐S) scale to estimate clinically meaningful and clinically substantial changes as measured using the Montgomery‐Åsberg Depression Rating Scale (MADRS), the Sheehan Disability Scale (SDS), and the Patient Health Questionnaire‐9 (PHQ‐9) in patients with treatment‐resistant depression (TRD). Methods Pooled data were derived from two 4‐week, randomized, active‐controlled studies evaluating esketamine nasal spray (ESK) plus oral antidepressant (OAD) or OAD plus placebo nasal spray (PBO) in adults with TRD (N = 565). CGI‐S, MADRS, SDS, and PHQ‐9 scores were obtained at baseline and over 4 weeks of treatment. In this post hoc analysis, change scores on the MADRS, SDS, and PHQ‐9 that corresponded to a clinically meaningful (1‐point) or clinically substantial (2‐point) change on the CGI‐S scale were identified. Results Clinically meaningful changes in CGI‐S scores after 28 days corresponded to 6‐, 4‐, and 3‐point changes from baseline on the MADRS, SDS, and PHQ‐9, respectively. Similarly, a 2‐point CGI‐S score change (clinically substantial change) corresponded to a 12‐, 8‐, and 6‐point change on the MADRS, SDS, and PHQ‐9, respectively. The proportion of patients showing substantial clinical improvement in the ESK plus OAD group versus the OAD plus PBO group after 28 days of treatment favored ESK plus OAD: 69.0% vs 55.3% (MADRS), 64.5% vs 48.9% (SDS), and 77.1% vs 64.7% (PHQ‐9). Conclusion We provide a basis for identifying clinically meaningful and clinically substantial changes as assessed with commonly used outcome measures for depression to facilitate the translation of clinical trial results into clinical practice.

Study ObjectivesTo describe characteristics of veterans with MDD and the different treatment regimens received during the first observed and treated major depressive episode (MDE).MethodsA retrospective study was performed using the Veterans Health Administration (VHA) database from 4/1/2015 to 2/28/2019 (study period), supplemented with Medicare Part A/B/D data from 4/1/2015 to 12/31/2017. Adult veterans with ≥1 MDD diagnosis in the VHA database between 10/1/2015 and 2/28/2017 (index date) were included if they received ≥1 line of therapy (LOT) within a complete MDE. An MDE was considered as starting on the date of the first observed MDD diagnosis preceded by ≥6 months depression-free period (i.e. a period without an MDD diagnosis or antidepressant (AD) use); an MDE was considered as ended on the date of the last MDD diagnosis or the end of the medication supply of the last AD/augmentation medication, whichever came last and then followed by ≥6 months depression-free period. An MDE was required to begin and end during the study period. A LOT was defined as ≥1 AD at adequate dose and duration (≥6 weeks of continuous therapy with no gaps longer than 14 days) with or without an augmenting medication. Patients were required to have VA benefit enrollment for ≥6 months before (baseline) and ≥24 months after index (follow-up). Patient baseline demographic and clinical characteristics as well as the number and type of LOTs (up to the first six LOTs) received during the first observed and treated MDE were evaluated.ResultsOverall, 40,240 veterans with MDD were identified (mean ± standard deviation [SD] age: 50.9±16.3 years).The majority were male (83.9%), White (63.4%), and non-Hispanic (88.6%); 60.1% were unemployed or retired at some point during the study period. The most commonly observed baseline comorbidities included hypertension (27.5%), hyperlipidemia (20.8%), post-traumatic stress disorder (17.5%), and diabetes (14.8%). During the first observed and treated MDE (mean ± SD duration: 14.7 ± 8.6 months), patients received a mean of 1.6±1.0 LOTs, with 36.5% and 14.6% of patients receiving ≥2 and ≥3 LOTs, respectively; 0.8% of patients received ≥6 LOTs. The most commonly observed therapies were SSRI monotherapy (58.9%) followed by SNRI monotherapy (8.8%) in LOT1; SSRI monotherapy followed by AD augmented with anticonvulsants in LOT2 (SSRI monotherapy: 48.7%; AD augmentation with anticonvulsants:12.1%) and LOT3 (SSRI monotherapy: 43.5%; AD augmentation with anticonvulsants:15.0%).ConclusionsThis study used an episodic approach to evaluate the current standard of care among veterans with MDD. During the first observed and treated MDE, about one in seven veterans received ≥3 LOTs, suggesting presence of treatment-resistant MDD. Monotherapy with SSRIs or SNRIs and combination therapies of AD with anticonvulsants were the most common therapies in the first three LOTs.FundingJanssen Scientific Affairs, LLC

Aim To assess whether the secular trends in type 2 diabetes prevalence differ between abdominally obese and non‐obese individuals. Methods Data from the National Health and Nutrition Examination Surveys (NHANES) were used to estimate the prevalence of type 2 diabetes and abdominal obesity among individuals aged ≥20 years in the USA from 1999/2000 to 2013/2014, after standardization to the age, sex and ethnicity population distribution estimates on January 1, 2014, as published by the US Census Bureau. Results The prevalence of abdominal obesity in the US population increased from 47.4% (95% confidence interval [CI] 42.6‐52.2) in 1999/2000 to 57.2% (95% CI 55.9‐58.5) in 2013/2014. A significant increase was observed in all age groups: 20 to 44, 45 to 64, and ≥65 years. The prevalence of type 2 diabetes has also increased from 8.8% (95% CI 7.2‐10.4) in 1999/2000 to 11.7% (95% CI 10.9‐12.6) in 2013/2014, with no substantial change in trend over the recent years. However, the increase in the prevalence of type 2 diabetes was limited to individuals with abdominal obesity, and more specifically to individuals aged ≥45 years with abdominal obesity, with no significant change in prevalence in the non‐obese group and in individuals aged

Objectives To estimate the impact of increased glycated hemoglobin (A1C) monitoring and treatment intensification for patients with type 2 diabetes (T2D) on quality measures and reimbursement within the Medicare Advantage Star (MA Star) program. Methods The primary endpoint was the share of patients with T2D with adequate A1C control (A1C ≤ 9%). We conducted a simulation of how increased A1C monitoring and treatment intensification affected this end point using data from the National Health and Nutrition Examination Survey and clinical trials. Using the estimated changes in measured A 1C levels, we calculated corresponding changes in the plan-level A 1C quality measure, overall star rating, and reimbursement. Results At baseline, 24.4% of patients with T2D in the average plan had poor A1C control. The share of plans receiving the highest A1C rating increased from 27% at baseline to 49.5% (increased monitoring), 36.2% (intensification), and 57.1% (joint implementation of both interventions). However, overall star ratings increased for only 3.6%, 1.3%, and 4.8% of plans, respectively, by intervention. Projected per-member per-year rebate increases under the MA Star program were $7.71 (monitoring), $2.66 (intensification), and $10.55 (joint implementation). Conclusions The simulation showed that increased monitoring and treatment intensification would improve A1C levels; however, the resulting average increases in reimbursement would be small.

To compare healthcare costs of adults with type 2 diabetes (T2D) after initiation of saxagliptin or linagliptin, two antidiabetic medications in the dipeptidyl peptidase-4 inhibitor medication class.Patients with T2D who were at least 18 years old and initiated saxagliptin or linagliptin (index date) between 1 June 2011 and 30 June 2014 were identified in the MarketScan Commercial and Medicare Supplemental Databases. All-cause healthcare costs and diabetes-related costs (T2D diagnosis on a medical claim and/or an antidiabetic medication claim) were measured in the 1 year follow-up period. Saxagliptin and linagliptin initiators were matched using propensity score methods. Cost ratios (CRs) and predicted costs were estimated from generalized linear models and recycled predictions.There were 34,560 saxagliptin initiators and 18,175 linagliptin initiators identified (mean ages 57 and 59; 55% and 56% male, respectively). Before matching, saxagliptin initiators had significantly lower all-cause total healthcare costs than linagliptin initiators (mean = $15,335 [SD $28,923] vs. mean = $20,069 [SD $48,541], p .001) and significantly lower diabetes-related total healthcare costs (mean = $6109 [SD $13,851] vs. mean = $7393 [SD $26,041], p .001). In matched analyses (n = 16,069 per cohort), saxagliptin initiators had lower all-cause follow-up costs than linagliptin initiators (CR = 0.953, 95% CI = 0.932-0.974, p .001; predicted costs = $17,211 vs. $18,068). There was no significant difference in diabetes-related total costs after matching; however, diabetes-related medical costs were significantly lower for saxagliptin initiators (CR = 0.959, 95% CI = 0.927-0.993, p = 0.017; predicted costs = $3989 vs. $4159).Adult patients with T2D initiating treatment with saxagliptin had lower total all-cause healthcare costs and diabetes-related medical costs over 1 year compared with patients initiating treatment with linagliptin.

DISCLOSURES: The writing of this letter was supported by Janssen Scientific Affairs. The authors are employees of Janssen Scientific Affairs or Janssen Global Services (Johnson & Johnson).

Objectives: To assess characteristics and healthcare costs associated with pharmacologically-treated episodes of treatment-resistant depression (TRD) in patients with major depressive disor...

BackgroundPrevious studies have assessed the incremental economic burden of treatment-resistant depression (TRD) versus non-treatment-resistant major depressive disorder (i.e., non-TRD MDD) in commercially-insured and Medicaid-insured patients, but none have focused on Medicare-insured patients.ObjectiveTo assess healthcare resource utilization (HRU) and costs of patients with TRD versus non-TRD MDD or without major depressive disorder (MDD; i.e., non-MDD) in a Medicare-insured population.MethodsAdult patients were retrospectively identified from the Chronic Condition Warehouse de-identified 100% Medicare database (01/2010-12/2016). MDD was defined as ≥1 MDD diagnosis and ≥1 claim for an antidepressant. Patients initiated on a third antidepressant following two antidepressant treatment regimens of adequate dose and duration were considered to have TRD. The index date was defined as the date of the first antidepressant claim for the TRD and non-TRD MDD cohorts, and as a randomly imputed date for the non-MDD cohort. Patients with TRD were matched 1:1 to non-TRD MDD patients and randomly selected non-MDD patients based on propensity scores. Analyses were also performed for a subset of patients aged ≥65.ResultsOf 29,543 patients with MDD, 3,225 (10.9%) met the study definition of TRD; 157,611 were included in the non-MDD cohort. Matched patients with TRD and non-TRD MDD were, on average, 58.9 and 59.0 years old, respectively. The TRD cohort had higher per-patient-per-year (PPPY) HRU than the non-TRD MDD (e.g., inpatient visits: incidence rate ratio [IRR] = 1.36) and non-MDD cohorts (e.g., inpatient visits: IRR = 1.84, all PConclusionAmong Medicare-insured patients, those with TRD had higher HRU and costs compared to those with non-TRD MDD and non-MDD.

Objective Our objective was to assess healthcare resource utilization (HRU) and costs among patients with major depressive disorder (MDD) with and without treatment-resistant depression (TRD) and those without MDD in US Integrated Delivery Networks (IDNs). Methods This was a retrospective matched-cohort study. The Optum© Integrated Claims Electronic Health Record de-identified database was used to identify adult patients with TRD (January 2011–June 2017) across US IDNs. TRD patients were propensity score matched 1:1 with non-TRD MDD and non-MDD patients on demographics. Rates of HRU and costs were compared up to 2 years following the first antidepressant pharmacy claim (or randomly imputed date for non-MDD patients) using negative binomial and ordinary least squares regressions, respectively, with 95% confidence intervals (CIs) from nonparametric bootstraps (costs only) adjusted for baseline comorbidity index and costs. Results All 1582 TRD patients were matched to non-TRD MDD and non-MDD patients and evaluated. TRD patients were on average 46 years old, and 67% were female. Mean duration of observation was 20.1, 19.6, and 17.9 months in the TRD, non-TRD MDD, and non-MDD cohorts, respectively. Patients with TRD had significantly higher rates of HRU than did non-TRD MDD patients (inpatient visits 0.35 vs. 0.16 per patient per year [PPPY]; adjusted incidence rate ratio [IRR] 2.04 [95% CI 1.74–2.39]) and non-MDD patients (0.35 vs. 0.09 PPPY, adjusted IRR 3.05 [95% CI 2.54–3.66]). TRD patients incurred significantly higher costs PPPY than did non-TRD MDD patients ($US25,807 vs. 13,701, adjusted cost difference $US9479 [95% CI 7071–11,621]) and non-MDD patients ($US25,807 vs. 8500, adjusted cost difference $US11,433 [95% CI 8668–13,876]). Conclusions HRU and costs associated with TRD are significant in US IDNs. Electronic supplementary material The online version of this article (10.1007/s41669-019-0154-z) contains supplementary material, which is available to authorized users.

Among patients with major depressive disorder (MDD), those with treatment-resistant depression (TRD) have a higher economic burden. However, the healthcare resource utilization (HRU) and costs may vary by severity status in TRD patients. This study quantified the incremental economic burden of severity status in TRD patients.In a US database of privately insured employees and dependents (07/01/2009-03/31/2015), a claims-based algorithm identified adult TRD patients who were stratified into mild, moderate, and severe cohorts based on the information in the last observed MDD ICD-9-CM code. HRU and costs of moderate and severe cohorts were compared to those of the mild cohort during the 2-year follow-up after the first antidepressant claim.Among 6411 TRD patients, 455 (7.1%) were identified as mild, 2153 (33.6%) as moderate, and 1455 (22.7%) as severe. Moderate and severe patients compared to mild had 45% and 150% more inpatient admissions, 65% and 164% more inpatient days, 18% and 54% more emergency department visits and 8% and 10% more outpatient visits per-patient-per-year (PPPY), respectively (all-cause; all p 0.05). Mean all-cause direct total healthcare costs were $12,123, $16,885, and $18,911 PPPY in mild, moderate, and severe patients, respectively. The all-cause total healthcare cost differences adjusted for baseline characteristics amounted to $3455 in moderate and $5150 in severe versus mild patients, respectively (PPPY; all p 0.05).Not all TRD patients had a severity specifier; the severity specifier was not cross-validated against a depression scale.Increased severity status is associated with incremental economic burden in TRD patients.

BackgroundTreatment-resistant depression (TRD) may represent a substantial proportion of major depressive disorder (MDD); however, the risk of mortality in TRD is still incompletely assessed.MethodsData were obtained from Optum Clinformatics™ Extended, a US claims database. Date of the first antidepressant (AD) dispensing was designated as the index date for study entry and 6 months prior to that was considered the baseline period. Patients with MDD aged ≥ 18 years, index date between January 1, 2008 and September 30, 2015, no AD claims during baseline, and continuous enrollment in the database during baseline were included. Patients who started a third AD regimen after two regimens of appropriate duration were included in the TRD cohort. All-cause mortality was compared between patients with TRD and non-TRD MDD using a proportional hazards model and Kaplan–Meier estimate with TRD status being treated as a time-varying covariate. The model was adjusted for study year, age, gender, depression diagnosis, substance use disorder, psychiatric comorbidities, and Charlson comorbidity index.ResultsOut of 355,942 patients with MDD, 34,176 (9.6%) met the criterion for TRD. TRD was associated with a significantly higher mortality compared with non-TRD MDD (adjusted HR: 1.29; 95% CI 1.22–1.38;p p ConclusionsPatients with TRD had a higher all-cause mortality compared with non-TRD MDD patients.

[This corrects the article DOI: 10.1371/journal.pone.0223255.].

Background The use of quality measures attempts to improve safety and health outcomes and to reduce costs. In two Phase III trials in treatment-naive patients with type 2 diabetes, dapagliflozin 5 or 10 mg/d as initial combination therapy with metformin extended-release (XR) significantly reduced glycated hemoglobin (A1C) from baseline to 24 weeks and allowed higher proportions of patients to achieve A1C

R Brett McQueen,1 Vahram Ghushchyan,1,2 Temitope Olufade,3 John J Sheehan,4 Kavita V Nair,1 Joseph J Saseen1,5 1Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Anschutz Medical Campus, Aurora, CO, USA; 2College of Business and Economics, American University of Armenia, Yerevan, Armenia; 3AstraZeneca, Wilmington, DE, 4AstraZeneca, Fort Washington, PA, 5Department of Family Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA Objective: Estimate the economic burden associated with incremental increases in the number of cardiometabolic risk factors (CMRFs) in the US. Methods: We used the nationally representative Medical Expenditure Panel Survey from 2010 to 2012 to create a retrospective cohort of people based on the number of CMRFs (one, two, and three or four), and a comparison cohort of people with zero CMRFs. CMRFs included abdominal obesity, elevated blood pressure, elevated triglycerides, and elevated glucose andwere defined using diagnostic codes, prescribed medications, and survey responses. Adjusted regression analysis was developed to compare health expenditures, utilization, and lost-productivity differences between the cohorts. Generalized linear regression was used for health care expenditures, and negative binomial regression was used for utilization and productivity, controlling for individual characteristics. Results: The number of CMRFs was associated with significantly more annual utilization, health care expenditures, and reduced productivity. As compared with people with zero CMRFs, people with one, two, and three or four CMRFs had 1.15 (95% confidence interval [CI]: 1.06, 1.24), 1.37 (95% CI: 1.25, 1.51), and 1.39 (95% CI: 1.22, 1.57) times higher expected rate of emergency room visits, respectively. Compared with people with zero CMRFs, people with one, two, and three or four CMRFs had increased incremental health care expenditures of US$417 (95% CI: $70, $763), US$2,326 (95% CI: $1,864, $2,788), and US$4,117 (95% CI: $3,428, $4,807), respectively. Those with three or four CMRFs reported employment of 60%, compared with 80% in patients with zero CMRFs. People with three or four CMFRs had 1.75 (95% CI: 1.42, 2.17) times higher expected rate of days missed at work due to illness, compared with people with zero CMRFs. Conclusion: Our findings demonstrate a direct association between economic burden and number of CMRFs. Although this was expected, the increase in burden that was independent from the cost of cardiovascular disease was surprising. Keywords: economic burden, cardiometabolic risk factors, cardiovascular disease

ObjectiveThe economic burden of commercially insured patients in the United States with treatment-resistant depression and patients with non-treatment-resistant major depressive disorder was compared using data from the Optum Clinformatics™ claims database.MethodsPatients 18-63 years on antidepressant treatment between 1/1/13 and 9/30/13, who had no treatment claims for depression 6 months before the index date (first antidepressant dispensing), and who had a major depressive disorder or depression diagnosis within 30 days of the index date, were included. Treatment-resistant depression was defined as receiving 3 antidepressant regimens during 1 major depressive disorder episode. Patients with treatment-resistant depression were matched with patients with non-treatment-resistant major depressive disorder at a 1:4 ratio using propensity score matching. The study consisted of 1-year baseline (pre-index) and 2-year follow-up (post index) periods. Cost outcomes were compared using a generalized linear model.Results2,370 treatment-resistant depression and 9,289 non-treatment-resistant major depressive disorder patients were included. In year 1 of the follow-up period, compared with non-treatment-resistant major depressive disorder, patients with treatment-resistant depression had: more emergency department visits (odds ratio = 1.39, 95% confidence interval = 1.24-1.56); more inpatient hospitalizations (odds ratio = 1.73, 95% confidence interval = 1.46-2.05); longer hospital stays (mean difference vs non-treatment-resistant major depressive disorder = 2.86, 95% confidence interval = 0.86-4.86 days); and more total healthcare costs (mean difference vs non-treatment-resistant major depressive disorder = US$3,846, 95% confidence interval = $2,855-$4,928). These patterns remained consistent in year 2 of the follow-up period.ConclusionTreatment-resistant depression was associated with higher healthcare resource utilization and costs versus non-treatment-resistant major depressive disorder in this commercially insured cohort of patients in the United States.

This study aimed to evaluate hospital length of stay (LOS) and cost as well as readmission risk and the associated economic burden among patients hospitalized for treatment-resistant and non-treatment-resistant major depressive disorder.Adult patients with a primary hospital discharge diagnosis of major depressive disorder were identified from the Premier Hospital Database (January 1, 2012-September 30, 2015). Patients were stratified into two cohorts: those whose hospital treatment was suggestive of treatment-resistant depression and those with non-treatment-resistant depression. Hospital LOS and cost during the initial admission and readmissions rates, LOS, and cost within the 6-month follow-up were compared between cohorts with a propensity score-matched sample.After matching, 45,066 patients were included in each cohort. For index hospitalizations, mean hospital LOS was longer (7.4 vs. 5.9 days, p0.001) and mean hospital cost higher ($8,681 vs. $6,632, p0.001) for patients with treatment-resistant depression vs. non-treatment-resistant depression. Rates for all-cause (24.4% vs. 20.0%, p0.001), major depressive disorder-related (17.0% vs. 13.3%, p0.001), and suicidal ideation/suicide attempt-related (12.8% vs. 9.5%, p0.001) readmissions were higher for patients with treatment-resistant depression. Mean LOS and total hospital costs per patient for readmissions were also greater for patients with treatment-resistant depression vs. non-treatment-resistant depression. Correspondingly, the combined hospital cost (index hospitalization+all-cause readmissions) was greater for patients with treatment-resistant depression ($12,370 vs. $9,429, p0.001).Treatment-resistant depression was associated with substantial economic burden among patients hospitalized for major depressive disorder. More-effective treatment and care for this patient population may reduce the hospital burden of patients with treatment-resistant depression.

The authors discuss a simple strategy for payers to ensure more patients with type 2 diabetes achieve control of A1C.

This study examined the relationship between medication adherence, cost sharing measured as out-of-pocket spending, and total annual spending in Medicare beneficiaries with type 2 diabetes (T2D) to evaluate whether pharmacy cost-sharing programs have the potential to decrease adherence. These programs may unintentionally increase the risk of medical complications and may result in higher spending overall.This retrospective study used 2006 to 2009 Medicare claims data. The sample included patients 65 years or older with T2D (at least 1 claim with International Classification of Diseases, 9th Revision, Clinical Modification codes 250.x0 and 250.x2 and at least 1 antidiabetes drug claim).Medication adherence was measured as proportion of days covered over the first 12 months of observation. Spending and adherence outcomes were defined in deciles.The sample included 12,305 patient-year observations. Pharmacy spending for patients in the most adherent (10th) decile was 59% higher than that for patients in the least adherent (1st) decile ($4839 vs $3046). Yet, patients in the 10th decile had 49% lower total ($12,531 vs $24,468) and 64% lower medical spending ($7692 vs $21,421) than patients in the 1st decile. Greater out-of-pocket spending was correlated with lower adherence and higher total and medical spending.This study describes a widespread variation in medication adherence, pharmacy cost sharing, and medical spending in a sample of Medicare beneficiaries with T2D. We found that lower adherence was correlated with higher cost sharing in the Medicare population, perhaps because of unobserved confounding factors. However, the existing literature on patients with employer-sponsored insurance suggests some of this correlation may be indicative of causal relationships.

Background: Although practice guidelines stress individualization of glucose management in patients with type 2 diabetes (T2D), the extent to which providers take patient factors into account when selecting medications is not well known. We used data from DCR to evaluate the current real-world landscape of glucose-lowering drugs in key subsets of patients with T2D. Methods: DCR is the first large-scale US outpatient registry of patients with diabetes recruited from cardiology, endocrinology, and primary care practices and currently encompasses 374 practices and 5114 providers. T2D medications were grouped as those which are suboptimal for patients with 1) obesity: insulin, sulfonylurea, TZD; 2) elderly (i.e., high hypoglycemia risk): insulin, sulfonylurea; 3) CKD 4/5: metformin, sulfonylurea; and 4) CV disease: sulfonylurea. We examined patient factors associated with use of these groups of meds using 4 hierarchical (for both specialty and site) modified Poisson models, adjusting for HbA1c, number of T2D meds, and insurance. Results: Overall, 157,551 patients with T2D were prescribed a med for glycemic control: metformin 75%, sulfonylurea 34%, insulin 28%, DPP-4i 18%, TZD 11%, GLP-1 RA 6.4%, SGLT2i 4.8%. After adjusting patient factors, glycemic control, and insurance status, patients with higher BMIs were more likely treated with medications prone to cause weight gain (obesity class I/II: rate ratio [RR] 1.02, 95% CI 1.00-1.03; obesity class III: RR 1.09, 95% CI 1.05-1.12). Older patients were more likely to be treated with meds with increased risk of hypoglycemia (RR 1.04 per 5 years, 95% CI 1.03-1.05). Patients with GFR less likely to be treated with meds with known risk in patients with CKD (RR 0.72, 95% CI 0.68-0.76). Patients with CAD were less likely to be treated with meds with known CV harm (RR 0.97, 95% CI 0.96-1.00). Conclusion: In a large US-based registry of T2D patients, we observed some targeted use of glucose-lowering therapy—in particular, patients with advanced CKD and CAD were not given meds known to be harmful to these patients. However, risk of hypoglycemia and risk of weight gain did not appear to factor substantially into decision making. As these are among several factors that go into drug selection for complicated patients with T2D, conclusions from these data are limited. Nonetheless, in an era of increasing number and complexity of medication choices with varying risk/benefits, databases like the DCR may allow investigators to assess these trends and to highlight potential areas for improvement in pharmacologic personalization, particularly as the use of newer drug classes grows.

Introduction Patients with type 2 diabetes mellitus (T2DM) must remain adherent and persistent on antidiabetic medications to optimize clinical benefits. This analysis compared adherence and persistence among adults initiating dipeptidyl peptidase-4 inhibitors (DPP-4is), sulfonylureas (SUs), and thiazolidinediones (TZDs) and between patients initiating saxagliptin or sitagliptin, two DPP-4is. Methods This retrospective cohort study utilized the US MarketScan® (Truven Health Analytics, Ann Arbor, MI, USA) Commercial and Medicare Supplemental health insurance claims databases. Adults aged ≥18 years with T2DM who initiated a DPP-4i, SU, or TZD from January 1, 2009 to January 31, 2012 were included. Patients must have been continuously enrolled for ≥1 year prior to and ≥1 year following initiation. Adherence was measured using proportion of days covered (PDC), with PDC ≥ 0.80 considered adherent. Persistence was measured as time to discontinuation, defined as last day with drug prior to a 60+ days gap in therapy. Multivariable logistic regression and Cox proportional hazards models compared the outcomes between cohorts, controlling for baseline differences. Results The sample included 238,372 patients (61,399 DPP-4i, 134,961 SU, 42,012 TZD). During 1-year follow-up, 47.3% of DPP-4i initiators, 41.2% of SU initiators, and 36.7% of TZD initiators were adherent. Adjusted odds of adherence were significantly greater among DPP-4i initiators than SU (adjusted odds ratio [AOR] = 1.678, P

Summary Background The efficacy of adjunctive aripiprazole in patients with major depressive disorder (MDD) with no improvement after 8 weeks of prior antidepressant monotherapy has not been evaluated. Methods A post hoc analysis of three similarly designed, randomised, double-blind, placebo-controlled, phase III studies was conducted investigating the efficacy and safety of aripiprazole adjunctive to standard antidepressant treatment (ADT) in MDD patients with a prior inadequate response to one to three ADTs. Minimal improvement to antidepressant monotherapy was defined as a Clinical Global Impressions – Improvement (CGI-I) score of 3 and non-improvement as a CGI-I of 4 at weeks 6 and 8 of antidepressant monotherapy. Results The end-point response rate for ADT minimal improvers receiving adjunctive aripiprazole was 38.8% vs. 26.6% for adjunctive placebo (p

This study evaluated the relationship between patient characteristics and augmentation strategies for the treatment of major depressive disorder.This retrospective, cross-sectional study used data from a psychiatric electronic medical record database for patients with depression without psychosis or psychotic features who initiated augmentation therapy between January 2001 and June 2011. Medical records were evaluated to identify factors predicting use of specific augmentation agents, and a multivariate logistic regression model was used to assess clinical and demographic predictors of augmentation strategy.Of 3,209 patients initiating augmentation therapy for depression, 75% received augmentation with an antidepressant combination and 11% received augmentation with second-generation antipsychotics. Baseline clinical severity (Clinical Global Impressions-Severity score) most strongly and consistently predicted augmentation with second-generation antipsychotics.Treatment of patients in specialty settings with depression was often augmented with an antidepressant combination, whereas those with severe depression had an increased likelihood of augmentation with second-generation antipsychotics.

Background There is a paucity of evidence for outcome predictors in patients with major depressive disorder (MDD) not responding to initial antidepressant therapy (ADT). This post-hoc analysis evaluated whether MDD severity affects response to adjunctive aripiprazole. Methods Data from 3 randomized, double-blind, placebo-controlled trials of adjunctive aripiprazole in adults with MDD and inadequate response to 1 to 3 ADT trials were pooled and stratified based on Montgomery–Asberg Depression Rating Scale (MADRS) total score (mild, ≤24; moderate, 25–30; severe, ≥31). Treatment differences in change in MADRS total score and rates of response (≥50% MADRS improvement) and remission (response with MADRS total score ≤10) were analyzed at endpoint. Adverse events were assessed within each subgroup. Results Aripiprazole produced greater improvement than placebo in the MADRS total score regardless of MDD severity at baseline (between-treatment difference [95% CI]: mild, −2.5 [−4.0 to −1.1]; moderate, −3.2 [−4.9 to −1.6]; severe, −4.5 [−6.8 to −2.2]). Compared with placebo, adjunctive aripiprazole increased the likelihood of response in all subgroups (risk ratio [95% CI]: mild, 1.50 [1.15, 1.95]; moderate, 1.51 [1.09, 2.11]; severe, 1.95 [1.23, 3.10]). Common treatment-emergent adverse events included akathisia and restlessness. Limitations The original studies were not designed to assess the efficacy of adjunctive aripiprazole by baseline severity, and this post-hoc analysis was not powered to evaluate differences in severity subgroups. Conclusions In patients who failed to respond to initial ADT, adjunctive aripiprazole was more effective than placebo in mild, moderate, and severe MDD strata. Clinical trial registration ClinicalTrial.gov: NCT00095823, NCT00105196, and NCT00095758.

Patients with schizophrenia often suffer from comorbid hepatic disease. This multicenter, open-label, single-arm, crossover study evaluated the safety and efficacy of paliperidone extended-release (ER) in patients with schizophrenia or schizoaffective disorder and hepatic disease.The study comprised a screening period, followed by 9 weeks' open-label treatment, divided into 2 phases. Phase 1 (4 weeks) was a continuation of usual antipsychotic treatment (UAT); phase 2 (5 weeks) consisted of a 1-week cross-titration from UAT to flexibly dosed paliperidone ER (3-12 mg/d), followed by 4 weeks of paliperidone ER alone. Treatment-emergent adverse events (TEAEs), including those considered more relevant to antipsychotic treatment (prespecified adverse events [AEs]), were analyzed.Although more subjects reported TEAEs during the paliperidone ER alone period than during the UAT period, no significant differences occurred in prespecified AE rates. No new safety signals were detected, and minimal shifts in liver function test values were observed. Improvements in psychiatric symptoms and functioning were observed after 4 weeks' paliperidone ER treatment.This study suggests that paliperidone ER is well tolerated in patients with schizophrenia or schizoaffective disorder and hepatic disease. To the best of our knowledge, this is the largest prospective study to date in this population.