Exploring humanistic burden of fatigue in adults with multiple sclerosis: an analysis of US National Health and Wellness Survey data.

BACKGROUND: This retrospective study examined the humanistic burden of fatigue in patients with relapsing-remitting multiple sclerosis (RRMS), compared with adults without MS, using data from the 2017 and 2019 US National Health and Wellness Survey. METHODS: The 5-item Modified Fatigue Impact Scale (MFIS-5) was used to assess level of fatigue (MFIS-5 score <15: low fatigue [LF]; MFIS-5 score ≥15: high fatigue [HF]) in patients with RRMS. Health-related quality of life (HRQoL) measures (Short Form 36-Item Health Survey version 2, Euroqol-5 Dimensions-5 Levels [EQ-5D-5L], Patient Health Questionnaire-9 [PHQ-9], Generalized Anxiety Disorder-7 [GAD-7], Perceived Deficits Questionnaire-5) and treatment-related characteristics were assessed. RESULTS: In total, 498 respondents were identified as RRMS (n=375 RRMS+LF, n=123 RRMS+HF) and compared with 1,494 matched non-MS controls. RRMS+LF and RRMS+HF had significantly lower Short Form 6 Dimensions health utility, Mental and Physical Component Summary, and EQ-5D-5L scores and higher PHQ-9 and GAD-7 scores, compared with matched non-MS controls (all p<0.001); scores were worse for RRMS+HF than RRMS+LF across all measures (all p<0.001). A higher proportion of RRMS+HF reported moderate-to-severe depression and moderate-to-severe anxiety, compared with RRMS+LF and matched non-MS controls (both p<0.001). Fatigue was a significant predictor of poor HRQoL across all measures (all p<0.001). CONCLUSIONS: Patients with RRMS experienced lower HRQoL with higher levels of fatigue, highlighting an unmet need. Results may help to inform physician-patient communication and shared decision-making to address fatigue and its associated impact on patients' HRQoL.

Robust paths to net greenhouse gas mitigation and negative emissions via advanced biofuels.

Biofuel and bioenergy systems are integral to most climate stabilization scenarios for displacement of transport sector fossil fuel use and for producing negative emissions via carbon capture and storage (CCS). However, the net greenhouse gas mitigation benefit of such pathways is controversial due to concerns around ecosystem carbon losses from land use change and foregone sequestration benefits from alternative land uses. Here, we couple bottom-up ecosystem simulation with models of cellulosic biofuel production and CCS in order to track ecosystem and supply chain carbon flows for current and future biofuel systems, with comparison to competing land-based biological mitigation schemes. Analyzing three contrasting US case study sites, we show that on land transitioning out of crops or pasture, switchgrass cultivation for cellulosic ethanol production has per-hectare mitigation potential comparable to reforestation and severalfold greater than grassland restoration. In contrast, harvesting and converting existing secondary forest at those sites incurs large initial carbon debt requiring long payback periods. We also highlight how plausible future improvements in energy crop yields and biorefining technology together with CCS would achieve mitigation potential 4 and 15 times greater than forest and grassland restoration, respectively. Finally, we show that recent estimates of induced land use change are small relative to the opportunities for improving system performance that we quantify here. While climate and other ecosystem service benefits cannot be taken for granted from cellulosic biofuel deployment, our scenarios illustrate how conventional and carbon-negative biofuel systems could make a near-term, robust, and distinctive contribution to the climate challenge.

A Choice-Based Conjoint Analysis of the Psychiatrist Decision-Making Process Used in Determining When to Discharge Adults With Major Depressive Disorder Hospitalized for Active Suicidal Ideation With Intent.

ABSTRACT: 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.

Clinically meaningful changes on depressive symptom measures and patient-reported outcomes in patients with treatment-resistant depression.

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.

Association of depression symptom severity with short-term risk of an initial hospital encounter in adults with major depressive disorder.

BACKGROUND: Despite the availability of pharmacologic and nonpharmacologic treatment options, depression continues to be one of the leading causes of disability worldwide. This study evaluated whether depression symptom severity, as measured by PHQ-9 score, of patients diagnosed with MDD is associated with short-term risk of a hospital encounter (ER visit or inpatient stay). METHODS: Adults with ≥1 PHQ-9 assessment in an outpatient setting (index date) and ≥ 1 MDD diagnosis within 6 months prior were included from the de-identified Optum Electronic Health Record database (April 2016-June 2019). Patients were categorized by depression symptom severity based on PHQ-9 scores obtained by natural language processing. Crude rates, adjusted absolute risks, and adjusted relative risks of all-cause and MDD-related hospital encounters within 30 days following assessment of depression severity were determined. RESULTS: The study population consisted of 280,145 patients with MDD and ≥ 1 PHQ-9 assessment in an outpatient setting. Based on PHQ-9 scores, 26.9% of patients were categorized as having none/minimal depression symptom severity, 16.4% as mild, 24.7% as moderate, 19.6% as moderately severe, and 12.5% as severe. Among patients with none/minimal, mild, moderate, moderately severe, and severe depression, the adjusted absolute short-term risks of an initial all-cause hospital encounter were 4.1, 4.4, 4.8, 5.6, and 6.5%, respectively; MDD-related hospital encounter adjusted absolute risks were 0.8, 1.0, 1.3, 1.6, and 2.1%, respectively. Compared to patients with none/minimal depression symptom severity, the adjusted relative risks of an all-cause hospital encounter were 1.60 (95% CI 1.50-1.70) for those with severe, 1.36 (1.29-1.44) for those with moderately severe, 1.18 (1.12-1.25) for those with moderate, and 1.07 (1.00-1.13) for those with mild depression symptom severity. CONCLUSIONS: These study findings indicate that depression symptom severity is a key driver of short-term risk of hospital encounters, emphasizing the need for timely interventions that can ameliorate depression symptom severity.

Assessment of yield gaps on global grazed-only permanent pasture using climate binning.

To meet rising demands for agricultural products, existing agricultural lands must either produce more or expand in area. Yield gaps (YGs)-the difference between current and potential yield of agricultural systems-indicate the ability to increase output while holding land area constant. Here, we assess YGs in global grazed-only permanent pasture lands using a climate binning approach. We create a snapshot of circa 2000 empirical yields for meat and milk production from cattle, sheep, and goats by sorting pastures into climate bins defined by total annual precipitation and growing degree-days. We then estimate YGs from intra-bin yield comparisons. We evaluate YG patterns across three FAO definitions of grazed livestock agroecosystems (arid, humid, and temperate), and groups of animal production systems that vary in animal types and animal products. For all subcategories of grazed-only permanent pasture assessed, we find potential to increase productivity several-fold over current levels. However, because productivity of grazed pasture systems is generally low, even large relative increases in yield translated to small absolute gains in global protein production. In our dataset, milk-focused production systems were found to be seven times as productive as meat-focused production systems regardless of animal type, while cattle were four times as productive as sheep and goats regardless of animal output type. Sustainable intensification of pasture is most promising for local development, where large relative increases in production can substantially increase incomes or "spare" large amounts of land for other uses. Our results motivate the need for further studies to target agroecological and economic limitations on productivity to improve YG estimates and identify sustainable pathways toward intensification.

An Evaluation of the Clinical and Economic Burden Among Older Adult Medicare-Covered Beneficiaries With Treatment-Resistant Depression.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 p <0.05). 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. CONCLUSIONS: 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.

All-cause mortality in patients with treatment-resistant depression: a cohort study in the US population.

BACKGROUND: Treatment-resistant depression (TRD) may represent a substantial proportion of major depressive disorder (MDD); however, the risk of mortality in TRD is still incompletely assessed. METHODS: Data 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. RESULTS: Out 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 < 0.0001). Survival time was significantly shorter in the TRD cohort compared with the non-TRD MDD cohort (p < 0.0001). CONCLUSIONS: Patients with TRD had a higher all-cause mortality compared with non-TRD MDD patients.

Recent trends in the prevalence of type 2 diabetes and the association with abdominal obesity lead to growing health disparities in the USA: An analysis of the NHANES surveys from 1999 to 2014.

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 <45 years. CONCLUSION: These findings highlight the critical importance of abdominal obesity-both as a likely key contributor to the continuing epidemic of type 2 diabetes in the USA and as a priority target for public health interventions.

Delays in treatment intensification with oral antidiabetic drugs and risk of microvascular and macrovascular events in patients with poor glycaemic control: An individual patient simulation study.

AIMS: To use the Archimedes model to estimate the consequences of delays in oral antidiabetic drug (OAD) treatment intensification on glycaemic control and long-term outcomes at 5 and 20 years. MATERIALS AND METHODS: Using real-world data, we modelled a cohort of hypothetical patients with glycated haemoglobin (HbA1c) ≥8%, on metformin, with no history of insulin use. The cohort included 3 strata based on the number of OADs taken at baseline. The first add-on in the intensification sequence was a sulphonylurea, next was a dipeptidyl peptidase-4 inhibitor, and last, a thiazolidinedione. The scenarios included either no delay or delay, based on observed and extrapolated times to intensification. RESULTS: At 1 year, HbA1c was 6.8% for patients intensifying without delay, and 8.2% for those delaying intensification. For no delay vs delay, risks of major adverse cardiac events, myocardial infarction, heart failure and amputations were reduced by 18.0%, 25.0%, 13.7%, and 20.4%, respectively, at 5 years; severe hypoglycaemia risk, however, increased to 19% for the no delay scenario vs 12.5% for delay. At 20 years, the results showed similar trends to those at 5 years. CONCLUSIONS: Timing of intensification of OAD therapy according to guideline recommendations led to greater reductions in HbA1c and lower risks of complications, but higher risks of hypoglycaemia than delaying intensification. These results highlight the potential impact of timely treatment intensification on long-term outcomes.

Value-Based Payments and Incentives to Improve Care: A Case Study of Patients with Type 2 Diabetes in Medicare Advantage.

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 A1C levels, we calculated corresponding changes in the plan-level A1C 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.

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

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

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

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

Real-world assessment of treatment inertia in the management of patients treated for major depressive disorder in the USA.

Aim: Major depressive disorder (MDD) is a debilitating illness in which depressive symptoms may persist after treatment. Treatment inertia is the continued use of the same pharmacotherapy regimen when treatment goals are not met. This study assessed the frequency of treatment inertia among adult patients with MDD treated in a real-world setting. Patients & methods: This was a retrospective, observational study of patients with MDD identified in the Decision Resources Group Real World Evidence US Data Repository from January 2014 to June 2018. Patients (≥18 years) had an elevated Patient Health Questionnaire-9 (PHQ-9) score (≥5) following 8 weeks of stable baseline antidepressant use with/without mental-health outpatient therapy. Treatment inertia, modification and discontinuation were evaluated over a 16-week follow-up period (timeline based on the APA Practice Guidelines). The primary outcome was the proportion of MDD patients experiencing treatment inertia. Results: 2850 patients (median age, 55 years; 74% female) met the study criteria. Of these patients, 834 (29%) had study-defined treatment inertia, 1534 (54%) received treatment modification and 482 (17%) discontinued treatment. Use of mirtazapine (Odd ratio [OR]: 0.63; 95% confidence interval [CI]: 0.50-0.79), selective serotonin reuptake inhibitors (OR: 0.64; 95% CI: 0.54-0.75) or bupropion (OR: 0.71; 95% CI: 0.60-0.84) in the baseline period was associated with an increased likelihood of treatment modification versus not receiving treatment with these medications. Frequency of treatment inertia may differ among those who do not have a documented PHQ-9 score. Conclusion: Effective symptom management is critical for optimal outcomes in MDD. Results demonstrate that treatment inertia is common in MDD despite guidelines recommending treatment modification in patients not reaching remission.

How Much Better is Faster? Value Adjustments for Health-Improvement Sequences.

While the quality-adjusted life-year construct has advantages of simplicity and consistency, simplicity requires strong assumptions. In particular, standard assumptions result in health-state utility functions that are unrealistically linear and separable in risk and duration. Consequently, sequencing of a series of health improvements has no effect on the total value of the sequence because each increment is assessed independently of previous increments. Utility functions in nearly all other areas of applied economics are assumed to be nonlinear with diminishing marginal utility so it matters where an improvement occurs in a sequence. We construct a conceptual framework that that demonstrates how diminishing marginal utility for health improvements could affect preferences for different sequence patterns. Using this framework, we derive conditions for which the sum of conventional health-state utilities understates, overstates, or approximates the sequence-sensitive value of health improvements. These patterns suggest the direction and magnitude of possible adjustments to conventional value calculations. We provide numerical examples and identify recent studies whose results are consistent with the conceptual model.

Predictors of response and remission in patients with treatment-resistant depression: A post hoc pooled analysis of two acute trials of esketamine nasal spray.

This exploratory post hoc analysis of two pooled 4-week, phase 3, double-blind, placebo- and active-controlled studies that compared esketamine nasal spray plus a newly initiated oral antidepressant (ESK+AD; n = 310) with a newly initiated oral AD plus placebo nasal spray (AD+PBO; n = 208) in patients with treatment-resistant depression (TRD) examined baseline patient demographic and psychiatric characteristics as potential predictors of response (≥50% reduction from baseline in Montgomery-Åsberg Depression Rating Scale [MADRS] total score) and remission (MADRS total score ≤12) at day 28. Overall, younger age, any employment, fewer failed ADs in the current depressive episode, and reduction in Clinical Global Impression-Severity (CGI-S) score at day 8 were significant positive predictors of response and remission at day 28. Treatment assignment was an important predictor of both response and remission. Patients treated with ESK+AD had 68% and 55% increased odds of achieving response and remission, respectively, versus those treated with AD+PBO. In the ESK+AD group, attainment of response and remission was more likely in patients who were employed, without significant anxiety at baseline, and who experienced a reduction in CGI-S score at day 8. Identification of predictors of response and remission may facilitate identification of those patients with TRD most likely to benefit from ESK+AD. Trial Registration: ClinicalTrials.gov: NCT02417064 (clinicaltrials.gov/ct2/show/NCT02417064) and NCT02418585 (clinicaltrials.gov/ct2/show/NCT02418585).

US budget impact analysis of esketamine nasal spray in major depressive disorder with acute suicidal ideation/behavior.

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.

Assessment of economic burden of fatigue in adults with multiple sclerosis: An analysis of US National Health and Wellness Survey data.

BACKGROUND: Fatigue, a common disabling symptom in multiple sclerosis (MS), is reported by the majority of patients. However, evidence on the economic burden of fatigue in MS by fatigue status is limited. This study aimed to evaluate the economic burden of fatigue, including healthcare resource utilization (HCRU), labor force participation, and Work Productivity and Activity Impairment (WPAI), among adults with relapsing-remitting MS (RRMS) by low fatigue (LF) vs high fatigue (HF) and compared with adults without MS. METHODS: This cross-sectional, retrospective, observational study included pooled data from the 2017 and 2019 US National Health and Wellness Survey. The RRMS sample included respondents aged ≥18 years who reported being diagnosed with MS by a healthcare provider (HCP) and reported having RRMS. Non-MS controls included respondents aged ≥18 years who did not report being diagnosed with MS by an HCP. Fatigue was measured using the Modified Fatigue Impact Scale-5 (MFIS-5). Outcomes included HCRU (HCP visits, emergency department visits, and hospitalizations in the past 12 months), labor force participation (yes vs no), WPAI (absenteeism, presenteeism, total work productivity impairment, and activity impairment), and annualized costs (direct medical, indirect, and total). Respondents with RRMS were propensity-score matched to non-MS controls (ratio 1:3). RRMS respondents were categorized as having LF (MFIS-5<15; RRMS+LF) and HF (MFIS-5≥15; RRMS+HF). Bivariate analysis compared matched non-MS controls, RRMS+LF, and RRMS+HF. Multivariable analyses were conducted among RRMS to evaluate associations between fatigue (continuous variable) and outcomes. RESULTS: Overall, 498 respondents with RRMS (RRMS+LF, n=375; RRMS+HF, n=123) and 1494 matched non-MS controls were included. RRMS+HF and RRMS+LF had more HCRU in the past 12 months than non-MS controls, whereas RRMS+HF had greater HCRU than RRMS+LF (all p<0.05). WPAI was also higher among RRMS+HF and RRMS+LF, compared with non-MS controls, as well as higher in RRMS+HF vs RRMS+LF (all p<0.001). RRMS+HF had significantly higher annualized direct medical costs than RRMS+LF and matched non-MS controls ($19,978 vs $10,656, p=0.007; vs $8,048, p<0.001). Among employed respondents, RRMS+HF and RRMS+LF had higher annualized indirect costs than non-MS controls, with RRMS+HF also having higher annualized indirect costs than RRMS+LF ($23,647 vs $13,738 vs $8,001; all p<0.01); total annualized costs were higher in RRMS+HF and RRMS+LF, compared with non-MS controls, as well as RRMS+HF vs RRMS+LF (all p<0.01). In multivariable models, fatigue was significantly and positively associated with the number of HCP visits in the past 12 months (p=0.002); not participating in the labor force (p<0.001); and absenteeism, presenteeism, total work productivity impairment, and activity impairment (all p<0.001). CONCLUSION: RRMS poses a substantial economic burden on patients and society, and this burden is disproportionately associated with HF.

Excess healthcare resource utilization and healthcare costs among privately and publicly insured patients with major depressive disorder and acute suicidal ideation or behavior in the United States.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: SIB are underreported in claims; unobserved confounders may cause bias. CONCLUSIONS: 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.