Healthcare resource utilization and costs among patients with post-stroke spasticity before and after spasticity management including onabotulinumtoxina.

BACKGROUND: Real-world data regarding the impact of onabotulinumtoxinA on healthcare resource utilization and costs for post-stroke spasticity are scarce. OBJECTIVE: To compare differences in 12-month healthcare resource utilization and costs before and after post-stroke spasticity management including onabotulinumtoxinA. METHODS: This retrospective claims analysis of IBM MarketScan Commercial and Medicare Supplemental databases included adults with ≥ 1 onabotulinumtoxinA claim for post-stroke spasticity (1 January 2010 to 30 June 2018) and continuous enrolment for ≥ 12 months pre- and post-index (first onabotulinumtoxinA claim date). All-cause and spasticity-related healthcare resource utilization and costs were compared 12 months pre- and post-index (McNemar's χ2 test or paired t-test). A subgroup analysis assessed effect of stroke-to-index interval on costs. RESULTS: Among 735 patients, mean (standard deviation) stroke-date-to-index-date interval was 284.5 (198.8) days. Decreases were observed post-index for mean all-cause outpatient (62.9 vs 60.5; p ≤ 0.05) and emergency department visits (1.1 vs 0.8; p ≤ 0.0001), and hospital admissions (1.5 vs 0.4; p ≤ 0.0001). Increase in prescription fills (43.0 vs 53.7) was seen post-index. Post-index decreases in all-cause (-66%) and spasticity-related (-51%) costs were driven by reduced inpatient care costs. Findings were consistent regardless of stroke-date-to-index-date interval. CONCLUSION: Significant reductions in healthcare resource utilization and costs were observed after 1 year of post-stroke spasticity management including onabotulinumtoxinA. Long-term studies are needed to establish causality.

Cost-effectiveness of overactive bladder treatments from a US commercial and payer perspective.

Aim: The cost-effectiveness of treatment options (anticholinergics, ß3-adrenoceptor agonists, onabotulinumtoxinA, sacral nerve stimulation and percutaneous tibial stimulation [the latter two including new rechargeable neurostimulators]) for the management of overactive bladder (OAB) were compared with best supportive care (BSC) using a previously published Markov model. Materials & methods: Cost-effectiveness was evaluated over a 15-year time horizon, and sensitivity analyses were performed using 2- and 5-year horizons. Discontinuation rates, resource utilization, and costs were derived from published sources. Results: Using Medicare and commercial costs over a 15-year time period, onabotulinumtoxinA 100U had incremental cost-effectiveness ratios (ICERs) gained of $39,591/quality-adjusted life-year (QALY) and $42,255/QALY, respectively, versus BSC, which were the lowest ICERs of all assessed treatments. The sensitivity analyses at 2- and 5-year horizons also showed onabotulinumtoxinA to be the most cost-effective of all assessed treatments versus BSC. Conclusion: OnabotulinumtoxinA 100U is currently the most cost-effective treatment for OAB.

Effectiveness and Safety of Chronic Migraine Preventive Treatments: A Systematic Literature Review.

INTRODUCTION: Numerous medications are used for the preventive treatment of chronic migraine (CM), including oral treatments, onabotulinumtoxinA (onabotA; BOTOX), and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs). Despite substantial clinical trial evidence, less is published about the real-world experience of these treatments based on data routinely collected from a variety of sources. This systematic review assessed real-world evidence on the effectiveness and safety of preventive treatments for CM in adults. METHODS: A systematic search of MEDLINE, Embase, and the Cochrane library with back-referencing and supplementary searches retrieved data published between January 2010 and February 2020. Publications were screened, extracted, and quality assessed. Data were narratively synthesized. Search criteria included preventive medications for CM. Evidence was available for topiramate, onabotulinumtoxinA, CGRP mAbs (erenumab, galcanezumab, and fremanezumab). OnabotulinumtoxinA was most commonly assessed (55 studies), followed by erenumab (six studies), multiple CGRP mAbs (one study), and topiramate (one study). Long-term data (> 1 year) were available for onabotulinumtoxinA only, with erenumab reported up 6 months, topiramate up to 3 months, and multiple CGRP mAbs up to 12 months. RESULTS: Substantial data demonstrated that onabotulinumtoxinA reduces the number/frequency of headaches, concomitant acute medication use, and impact of headaches on well-being and daily activity. More limited evidence showed benefits for the same parameters with erenumab. Single studies suggested topiramate and multiple CGRP mAbs decrease the number/frequency of headaches and impact of headaches. To date, onabotulinumtoxinA is the only preventive treatment for CM that has long-term safety data in real-world settings reporting treatment-related adverse events of up to 3 years. CONCLUSION: While substantial real-world evidence supports the long-term effectiveness and safety of onabotulinumtoxinA, real-world data on other preventive treatments of CM are currently limited to short term effectiveness due to their more recent approvals.

Treatment Patterns During Major Depressive Episodes Among Patients with Major Depressive Disorder: A Retrospective Database Analysis.

BACKGROUND: Major depressive disorder, a highly prevalent mental health condition, can be challenging to treat. OBJECTIVE: We aimed to characterize treatment patterns within and across multiple major depressive episodes in patients receiving treatment for major depressive disorder. METHODS: Adults with newly diagnosed major depressive disorder and one or more major depressive episodes were identified using the IBM® MarketScan® Commercial database. Eligible patients had 12 months of continuous enrollment before and after diagnosis. Lines of therapy were periods of continuous treatment with one or more antidepressant claims. Antidepressant, atypical antipsychotic, or mood stabilizer regimens as monotherapy or adjunctive therapy were characterized by lines of therapy and major depressive episodes. Descriptive analyses were performed. RESULTS: A total of 455,082 patients were included in the analysis. The majority of treatment regimens were monotherapy, which decreased with subsequent lines of therapy, while adjunctive treatments increased with subsequent lines of therapy. There were 1860 unique adjunctive regimens identified. Of the 40,315 patients (9%) who received adjunctive therapy, 8024 (20%; 2% of all patients) received atypical antipsychotic-adjunctive regimens. Only 19% of patients treated with atypical antipsychotic-adjunctive therapy discontinued treatment versus 42% of monotherapy-treated patients. On average, patients who received an adjunctive atypical antipsychotic received it as their third line of therapy and approximately 400 days after the initial antidepressant treatment. CONCLUSIONS: In this study, many patients continued monotherapy major depressive disorder regimens and experienced multiple treatment changes. Few patients were treated with adjunctive therapy. These results suggest underutilization of potentially effective treatments, which represents an opportunity to optimize the treatment of patients with major depressive disorder.

Health care resource utilization and costs associated with nonadherence and nonpersistence to antidepressants in major depressive disorder.

BACKGROUND: Nonadherence and nonpersistence to antidepressants in major depressive disorder (MDD) are common and associated with poor clinical and functional outcomes and increased health care resource utilization (HCRU) and costs. However, contemporary real-world evidence on the economic effect of antidepressant nonadherence and nonpersistence is limited. OBJECTIVE: To assess the effect of nonadherence and nonpersistence to antidepressants on HCRU and costs in adult patients with MDD enrolled in U.S. commercial and Medicare supplemental insurance plans. METHODS: This was a retrospective new-user cohort study using administrative claims data from the IBM MarketScan Commercial and Medicare Supplemental databases from January 1, 2010, to December 31, 2018. We identified adult patients with MDD aged ≥ 18 years who initiated antidepressant therapy for a new MDD episode between January 1, 2011, and December 31, 2017. Twelve-month total all-cause HCRU and costs (2019 U.S. dollars) were characterized for patients who were adherent/nonadherent and persistent/nonpersistent to antidepressants at 6 months. Adherence was defined as having proportion of days covered (PDC) ≥ 80%, and persistence was defined as having continuous antidepressant therapy without a ≥ 30-day gap. Multivariable negative binomial regression and 2-part models adjusted for baseline characteristics were used to estimate incidence rate ratios (IRRs) for HCRU and incremental costs of nonadherence and nonpersistence, respectively. RESULTS: A total of 224,645 patients with MDD (commercial: n = 209,422; Medicare supplemental: n = 15,223) met all study inclusion criteria. Approximately half of patients were nonadherent (commercial: 48%; Medicare supplemental: 50%) or nonpersistent (commercial: 49%; Medicare supplemental: 52%) to antidepressants at 6 months. After controlling for baseline characteristics, nonadherent patients experienced significantly more inpatient hospitalizations (commercial, adjusted IRR [95% CI]: 1.34 [1.29 to 1.39]; Medicare supplemental: 1.19 [1.12 to 1.28]) and emergency room (ER) visits (commercial, adjusted IRR [95% CI]: 1.43 [1.40 to 1.45]; Medicare supplemental: 1.28 [1.21 to 1.36]) compared with adherent patients. Similar results were observed in nonpersistent patients. Adjusted mean differences revealed that nonadherent and nonpersistent patients accumulated significantly higher medical costs (commercial: $568 [95% CI: $354 to $764] and $491 [$284 to $703]; Medicare supplemental: $1,621 [$314 to $2,774] and $1,764 [$451 to $2,925]), inpatient costs (commercial: $650 [$490 to $801] and $564 [$417 to $716]; Medicare supplemental: $1,546 [$705 to $2,308] and $1,567 [$778 to $2,331]), and ER costs (commercial: $130 [$115 to $143] and $129 [$115 to $142]; Medicare supplemental: $82 [$23 to $150] and $80 [$18 to $150]), and incurred significantly lower pharmacy costs (commercial: -$561 [-$601 to -$521] and -$576 [-$616 to -$540]; Medicare supplemental: -$510 [-$747 to -$227] and -$596 [-$830 to -$325]) compared with adherent and persistent patients, respectively. CONCLUSIONS: This study found more hospitalizations and ER use and higher total medical costs among patients who were nonadherent and nonpersistent to antidepressants at 6 months. Strategies that promote better adherence and persistence may lower HCRU and medical costs in patients with MDD. DISCLOSURES: This study was sponsored by Allergan, which was involved in the study design; data collection, analysis, and interpretation of data; and decision to present these results. Ta was supported by a training grant provided to the University of Washington by Allergan at the time this study was conducted. Tung and Gillard are employees of Allergan. Oliveri is an employee of Genesis Research. Sullivan and Devine have no financial disclosures. This study was presented as a poster at AMCP 2020 (Virtual Meeting), April 21-24, 2020.

Prevalence, treatment patterns, and stay characteristics associated with hospitalizations for major depressive disorder.

BACKGROUND: Hospitalizations for major depressive disorder (MDD) are a significant burden on patients, their families, and to healthcare systems. This study characterized the prevalence of MDD hospitalizations in the US and described clinical characteristics, treatment patterns, length of stay, costs, and MDD-related hospitalization readmissions. METHODS: A retrospective analysis of the Premier Perspective® Hospital Database was conducted using records of hospital admissions for MDD from January 1, 2014 to December 31, 2015. To supplement this analysis, healthcare claims data from Truven MarketScan® Research Database were also evaluated between January 1, 2013 and December 31, 2014. RESULTS: Among adult hospital stays in the Premier network, 1.3% included a primary diagnosis of MDD. The mean length of MDD-related stays was 6 days, with a mean total hospital charge per stay of $6713. Of those with hospital stays, 5.2% of patients had at least 1 readmission for MDD within 30 days of discharge. In the MarketScan database, 4% of adults with MDD had a MDD-related hospital stay, with a mean length of stay of 6 days and total reimbursed amount per stay of $8441. Of those with hospital stays, 5.4% had at least 1 readmission for MDD within 30 days. LIMITATIONS: Results may not be generalizable to hospitals outside of those represented by these databases. CONCLUSIONS: Adult MDD hospitalizations are costly and associated with high rates of readmission. There is a need for new treatments that may help reduce hospitalizations and costs related to hospitalizations in patients with MDD.

Economic Burden of Illness in Adult Patients with Nocturia.

BACKGROUND: Nocturia is considered to be a very bothersome lower urinary tract disorder. Yet, to date, the economic burden attributable to this poor health condition remains less well known. OBJECTIVE: To compare differences in health care resource utilization (HCRU), health care costs, and work productivity in adult patients with differing frequencies of nocturia episodes (i.e., < 2 vs. ≥ 2 nocturia episodes per night). METHODS: Adult patients with nocturia enrolled in an integrated proprietary database were recruited to complete a survey on their demographics, nocturia characteristics, and work productivity. Using patients' survey data and health care claims from the previous 6 months, those with < 2 (n = 197; 21.9%) versus ≥ 2 (n = 702; 78.1%) nocturia episodes per night were compared for differences in HCRU, health care costs, and work productivity after adjusting for potential confounders. HCRU was reported as the mean number per patient per month (PPPM) for outpatient visits (all types), physician office visits, and prescriptions filled and the proportion of patients with ≥1 hospitalization or emergency department visit in the previous 6 months. Health care costs were reported as mean PPPM. Work productivity was assessed via patient survey and reported as a mean percentage for absenteeism, presenteeism, overall work impairment, and activity impairment during the past week. RESULTS: 899 adult patients (mean age = 71.4 years; 57.2% men) were enrolled and analyzed. Compared with patients with <2 nocturia episodes per night, patients with ≥ 2 nocturia episodes had more outpatient health care visits (unadjusted mean visits PPPM: 2.1 vs. 1.6; P < 0.001; adjusted mean visits PPPM: 2.1 vs. 1.6; P = 0.017), office visits (unadjusted and adjusted mean visits PPPM: 0.9 vs. 0.7; P < 0.001), and prescriptions filled (unadjusted mean prescription fills PPPM: 3.1 vs. 2.1; P < 0.001; adjusted mean prescription fills PPPM: 3.2 vs. 2.2; P = 0.027). Patients with ≥ 2 nocturia episodes per night also displayed significantly higher outpatient health care costs (unadjusted mean PPPM costs: $676 vs. $516; P = 0.028; adjusted mean PPPM costs: $678 vs. $506; P = 0.017). In terms of work productivity impairment, patients with ≥ 2 nocturia episodes per night experienced higher rates of unadjusted (20% vs. 10%; P = 0.002) and adjusted presenteeism (20% vs. 10%; P = 0.004) and unadjusted (20% vs. 10%; P = 0.002) and adjusted overall work impairment (20% vs. 10%; P = 0.001). CONCLUSIONS: Study findings demonstrate that nocturia was associated with higher outpatient encounters and related costs in the presence of a greater occurrence of nocturic episodes. DISCLOSURES: This study was funded by Allergan plc, Dublin, Ireland. Neither honoraria nor payments were provided for authorship. Dmochowski is a consultant and speaker for Allergan plc and a consultant for Serenity Pharmaceuticals. Brucker is a consultant and speaker for Allergan plc, a consultant for Watkins-Conti and Avadel, and an investigator for Medtronic and Ipsen. Cole is a consultant for Allergan plc and an employee of Sharp Rees-Stealy Medical Group. Kawahara and Pulicharam are full-time employees of DaVita Medical Group. Burk is a consultant for Allergan plc and a health outcomes consultant. Tung is an employee of Allergan plc. Hale has served as a consultant/advisor to and has received research funding from Allergan plc. The data from this manuscript were previously presented in poster format by Steve Kawahara at the Academy of Managed Care & Specialty Pharmacy Annual Meeting; April 19-22, 2016; San Francisco, CA.

Employee organizational commitment and hospital performance.

BACKGROUND: There is widespread evidence of the purported benefits of employee organizational commitment (EOC) and its impact on both individual and organizational performance. This study contributes to this literature by providing a unique insight into this relationship, focusing on the interrelationship between EOC with hospital performance and the role of the provision of adequate facilities in eliciting EOC. PURPOSE: The aim of this study was to introduce and empirically examine a new theoretical model in which it is argued that the performance of hospitals with regard to the provision of adequate facilities (medical facilities, support facilities, and staff resources) influences the level of EOC, which in turn influences hospital performance with regard to patient care and operational effectiveness. METHODOLOGY/APPROACH: To examine the interrelationships between the provision of adequate facilities, EOC, and hospital performance, the study utilizes a survey of hospital managers. RESULTS: The findings support the theoretical model, with the provision of support facilities and staff resources positively indirectly associated with both patient care and operational effectiveness through their impact on EOC. CONCLUSION: The findings highlight the importance of providing adequate facilities and EOC within hospitals and suggest that CEOs and general managers should try to enhance the provision of such resources in an attempt to elicit EOC within their hospitals. PRACTICE IMPLICATIONS: The findings suggest that managers should try to enhance their provision of adequate facilities in order to elicit EOC and enhance hospital performance. With regard to medical facilities, they should consider and incorporate the latest technology and up-to-date equipment. They should also provide adequate staff resources, including appropriate numbers of beds, nurses, and doctors, to prevent "fatigue" (West, 2001, p. 41) and provide adequate support facilities.

Cost-effectiveness of overactive bladder treatments: from the US payer perspective.

AIM: To assess the cost-effectiveness of onabotulinumtoxinA (onabotA), implantable sacral nerve stimulation devices, percutaneous tibial nerve stimulation, anticholinergic medications and mirabegron compared with best supportive care (BSC) for management of refractory overactive bladder (OAB). METHODS: A Markov model was developed to compare the cost-effectiveness of treatment options with BSC over a 10-year time horizon. Resource utilization, discontinuation rates and costs were derived from unpublished and published sources. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were reported. RESULTS: Treatment with onabotA 100U produced the largest gain in QALYs (7.179) and lowest estimated incremental cost-effectiveness ratio ($32,680/QALY) of all assessed treatments compared with BSC. CONCLUSION: Compared with BSC, onabotA 100U was the most cost-effective treatment option for patients with refractory OAB.

Characterizing Health Care Utilization, Direct Costs, and Comorbidities Associated with Interstitial Cystitis: A Retrospective Claims Analysis.

BACKGROUND: Interstitial cystitis (IC) is a debilitating condition that affects up to 5% of the U.S. POPULATION: This condition is characterized by bladder pain, urinary urgency and frequency, nocturia, and, in some patients, bladder lesions called Hunner's lesions (HL). IC patients who have HL experience a clinical course that is distinct from those without HL and, as a result, respond differently to existing treatments. Without effective and lasting therapeutic options, IC patients are expected to experience a reduced quality of life and be a significant economic burden. Previous research describing the burden of IC is not only outdated but lacks stratification by HL. OBJECTIVES: To (a) characterize health care utilization, direct costs, and comorbidities associated with IC and (b) elucidate differences between patients with and without HL. METHODS: A retrospective analysis was conducted using health care claims from the Truven Health MarketScan Research Databases. Adults with an incident IC diagnosis between 2009 and 2014 were identified and matched 1:4 to non-IC patients on age, gender, and geographic region. Health care utilization, direct costs, and comorbidities during the first 12 months after diagnosis were compared between the 2 groups, as well as between IC subgroups with and without HL. Associations were evaluated after adjustment for potential confounders using regression models. RESULTS: A total of 24,836 IC patients were identified and matched to 99,344 non-IC patients. Patients were predominantly female (92%), with a mean age of 49.0 (SD = 15.3) years. IC patients used significantly more health care resources across all categories compared with non-IC patients. On average, having IC was associated with $7,223 higher total health care costs than not having IC (95% CI = $6,650-$7,796), with outpatient costs contributing to 71% of the difference, after adjusting for baseline age, gender, region, insurance type, plan type, and Charlson Comorbidity Index (CCI) score. The odds of developing select comorbidities were 2.61 times greater in IC patients compared with non-IC patients (95% CI = 2.52-2.70), adjusting for baseline age, sex, region, and CCI score. Among IC patients, the HL subgroup (n = 292) used more health care resources, and having HL was associated with $6,895 higher total health care costs compared with not having HL (95% CI = $3,770-$10,020) after adjusting for baseline age, gender, region, insurance type, and plan type. CONCLUSIONS: Findings suggest that patients with IC have significantly higher health care utilization, costs, and comorbidities compared with non-IC patients. This economic burden is further amplified in those with HL. DISCLOSURES: Funding for this study was contributed by Allergan. Tung was supported by a training grant from Allergan at the time of this study. Hepp was an Allergan employee at the time this study was conducted. The other authors have nothing to disclose. This research was previously presented, in part, as a poster presentation at the International Society for Pharmacoeconomics and Outcomes Research 21st Annual International Meeting; Washington, DC; May 23, 2016. Study concept and design were primarily contributed by Hepp, along with Tung and Devine. Tung took the lead in data collection, with assistance from Hepp, and data interpretation was performed by Tung, along with Bansal and Devine. The manuscript was prepared primarily by Tung, along with Devine, Bansal, and Hepp.

The relationship between organisational factors and the effectiveness of environmental management.

This paper examines the relationship between specific organisational factors (top management support, training, employee participation, teamwork and the link of performance to rewards) with the effectiveness of environmental management. The effectiveness of environmental management is measured in respect of the effectiveness of environmental management processes and environmental performance. Data were collected by mail survey questionnaire from a random sample of 899 senior financial officers in Australian manufacturing organisations. The findings highlight the significance of the effectiveness of environmental management processes as an antecedent of environmental performance and a mediator of the relationship between organisational factors and environmental performance. The findings provide managers with an insight into the specific organisational factors that they need to focus on to enhance the effectiveness of environmental management.

Startup circuit training program reduces metabolic risk in Latino adolescents.

PURPOSE: This study aimed to test the effects of a circuit training (CT; aerobic + strength training) program, with and without motivational interviewing (MI) behavioral therapy, on reducing adiposity and type 2 diabetes risk factors in Latina teenagers. METHODS: Thirty-eight Latina adolescents (15.8 ± 1.1 yr) who are overweight/obese were randomly assigned to control (C; n = 12), CT (n = 14), or CT + MI (n = 12). The CT classes were held twice a week (60-90 min) for 16 wk. The CT + MI group also received individual or group MI sessions every other week. The following were measured before and after intervention: strength by one-repetition maximum; cardiorespiratory fitness (V·O 2max) by submaximal treadmill test; physical activity by accelerometry; dietary intake by records; height, weight, waist circumference; total body composition by dual-energy x-ray absorptiometry; visceral adipose tissue, subcutaneous adipose tissue, and hepatic fat fraction by magnetic resonance imaging; and glucose/insulin indices by fasting blood draw. Across-intervention group effects were tested using repeated-measures ANOVA with post hoc pairwise comparisons. RESULTS: CT and CT + MI participants, compared with controls, significantly increased fitness (+16% and +15% vs -6%, P = 0.03) and leg press (+40% vs +20%, P = 0.007). Compared with controls, CT participants also decreased waist circumference (-3% vs +3%; P < 0.001), subcutaneous adipose tissue (-10% vs 8%, P = 0.04), visceral adipose tissue (-10% vs +6%, P = 0.05), fasting insulin (-24% vs +6%, P = 0.03), and insulin resistance (-21% vs -4%, P = 0.05). CONCLUSIONS: CT may be an effective starter program to reduce fat depots and improve insulin resistance in Latino youth who are overweight/obese, whereas the additional MI therapy showed no additive effect on these health outcomes.

Aerobic and strength training reduces adiposity in overweight Latina adolescents.

PURPOSE: To date, no study has examined the synergistic effects of a nutrition and combination of aerobic and strength training (CAST) on both adiposity and metabolic parameters in overweight Latina adolescent females. The goal was to assess if a 16-wk nutrition plus CAST pilot study had stronger effects on reducing adiposity and on improving glucose/insulin indices compared with control (C), nutrition only (N), and a nutrition plus strength training (N + ST) groups. METHODS: In a 16-wk randomized trial, 41 overweight Latina girls (15.2 +/- 1.1 yr) were randomly assigned to C (n = 7), N (n = 10), N + ST (n = 9), or N + CAST (n = 15). All intervention groups received modified carbohydrate nutrition classes (once a week), whereas the N + ST also received strength training (twice a week) and the N + CAST received a combination of strength and aerobic training (twice a week). The following were measured before and after intervention: strength by one repetition maximum, physical activity by the 7-d accelerometry and the 3-d physical activity recall, dietary intake by 3-d records, body composition by dual-energy x-ray absorptiometry (DEXA), glucose/insulin indices by oral glucose tolerance test, and intravenous glucose tolerance test with minimal modeling. Across intervention group, effects were tested using ANCOVA with post hoc pairwise comparisons. RESULTS: There were significant overall intervention effects for all adiposity measures (weight, body mass index [BMI], BMI z-scores, and DEXA total body fat), with a decrease of 3% in the N + CAST group compared with a 3% increase in the N + ST group (P < or = 0.05). There was also an intervention effect for fasting glucose with the N group increasing by 3% and the N + CAST group decreasing by 4% (P < or = 0.05). CONCLUSION: The CAST was more effective than nutrition alone or nutrition plus strength training for reducing multiple adiposity outcomes and fasting glucose in overweight Latina girls. However, further research investigating and identifying intervention approaches that improve both adiposity and insulin indices, particularly in high-risk populations, are warranted.