Reduced Hospitalizations and Amputations in Patients with Diabetic Foot Ulcers Treated with Cyclical Pressurized Topical Wound Oxygen Therapy: Real-World Outcomes.

Background: This study sought to examine the real-world impact of multimodality cyclical-pressure topical wound oxygen therapy (TWO2) on hospitalizations and amputations in patients with diabetic foot ulcer (DFU) compared with patients without TWO2. Methods: We conducted a retrospective review of deidentified patient medical records at 2 U.S. Veterans Affairs hospitals between January 2012 and January 2020. DFU patients were assigned to TWO2 or NO TWO2 cohorts based on their treatment records. Patients received appropriate standard of care and may have received other advanced wound treatments, including skin substitutes, negative pressure wound therapy, and growth factors. Primary study outcomes were patients requiring hospitalization and/or amputation within 360 days of initial wound documentation. Findings: Among unmatched cohorts of 202 patients with DFU (91 TWO2, 111 NO TWO2), 6.6% and 12.1% of TWO2 patients had hospitalizations and amputations, respectively, compared with 54.1% and 41.4% of NO TWO2 patients within 360 days (p < 0.0001, p < 0.0001), representing 88% and 71% reductions. Among propensity score-matched cohorts of 140 DFU patients (70 TWO2, 70 NO TWO2), compared with NO TWO2, 82% fewer TWO2 patients were hospitalized (7.1% vs. 40.0%, p < 0.0001) and 73% fewer TWO2 patients had amputations (8.6% vs. 31.4%, p = 0.0007). Logistic regression among matched cohorts demonstrated nearly ninefold and fivefold higher risk of hospitalization and amputation, respectively, for NO TWO2 versus TWO2. Interpretation: This retrospective cohort study demonstrates that treating patients with DFU with TWO2 is associated with significant reductions in hospitalizations and amputations in the real-world setting.

Correlation of disease comorbidity with prescribed treatment among insured U.S. lymphedema patients.

OBJECTIVE: The objective of this study was to define the current forms of treatment in a contemporary population of lymphedema (LED) patients for LED related to breast cancer, the most prevalently diagnosed LED comorbidity in Western countries, and phlebolymphedema with venous leg ulcer (PLEDU), a sequela of chronic venous disease. The goals of LED therapy are to reduce edema, thereby improving function and related symptoms, and to improve skin integrity to prevent development of infection. Treatment is generally nonsurgical: conservative care, including complex physical therapy, manual lymphatic drainage, and compression bandaging; or pneumatic compression device (PCD) therapy by a simple nonprogrammable device or an advanced programmable device. METHODS: To determine the frequency of individual types of treatment for LED and their relationship to breast cancer-related lymphedema (BCRL) and PLEDU, we queried claims from a deidentified Health Insurance Portability and Accountability Act-compliant commercial administrative insurance database with >165 million members. A total of 26,902 patients identified with LED who had been enrolled with continuous medical benefits for 12 months before and after the index date for the complete years 2012 through 2016 were separated into four treatment categories: no treatment, conservative care, simple PCD (SPCD), and advanced PCD. LED treatment was related to the BCRL and PLEDU comorbidities. RESULTS: BCRL patients, who represented 32.1% of all study patients, made up 41% of all patients receiving conservative care and 24% of patients receiving PCD therapy. By contrast, PLEDU patients (9.6% of study patients) were proportionally under-represented in the conservative care group (7.8%) but composed a disproportionately high share of the PCD therapy group (17.7%). PLEDU patients represented 23.5% of all LED patients prescribed SPCD therapy, whereas BCRL patients composed 10.3% of total LED patient SPCD prescriptions (P < .001). CONCLUSIONS: Our analysis of a large health care administrative database showed clear differences between the way BCRL and PLEDU patients are treated. Compared with BCRL patients, PLEDU patients were less likely to receive conservative care and more likely to be prescribed SPCDs for pneumatic compression therapy. These differences suggest that lymphatic therapy may be undervalued for treatment of chronic venous swelling and prevention and treatment of PLEDU.

Lymphedema-associated comorbidities and treatment gap.

BACKGROUND: Lymphedema (LE) has been called the forgotten vascular disease, given such scant knowledge about LE-associated comorbidities or causes. Such knowledge of the comorbidities and treatment of LE may assist in diagnostic decisions and health care planning. METHODS: To determine the proportion of LE patients with various LE-associated comorbidities as well as the rate of associated treatment, deidentified Health Insurance Portability and Accountability Act-compliant commercial administrative claims from the Blue Health Intelligence (BHI) research database (165 million Blue Cross Blue Shield members) were queried. We analyzed a BHI study sample of 26,902 patients with LE who had been enrolled with continuous medical benefits for 12 months before and after the index date for the complete years 2012 through 2016. Patients were first identified by comorbidity and then grouped into those receiving no treatment for LE and those receiving any treatment for LE. Any treatment was defined as receiving manual lymphatic drainage, physical therapy, compression garments, or a pneumatic compression device. The purpose of this study was to determine the proportion of LE patients comorbid with various known LE-associated conditions and the treatment rates of LE patients with each comorbidity. RESULTS: Among the 84,579,269 BHI patients enrolled during the study window, 81,366 patients were identified with LE. From this LE group, our study focused on the 26,902 patients who were enrolled with continuous medical and pharmacy benefits for 12 months before and after the index date. Among these 26,902 LE patients, breast cancer was the most frequent comorbidity with LE (32.1%), and these patients almost universally received any treatment (94.2%); other cancer types, such as melanoma (2.1%) and prostate cancer (0.7%), were less frequent and received any treatment less often, 75% and 82% of the time, respectively. Venous leg ulcer was the most common non-cancer-linked comorbidity for LE (9.6%), but only 81.7% of venous leg ulcer patients received any treatment for LE. CONCLUSIONS: To our knowledge, this is the largest study to date detailing the comorbidities associated with LE and LE treatment rates within each. Our findings suggest that a sizable proportion of cancer-related LE patients do not receive appropriate treatment. Furthermore, this study highlights the role of advanced venous disease as an LE comorbidity that is frequently untreated and its associated gap in treatment.

Health and economic benefits of advanced pneumatic compression devices in patients with phlebolymphedema.

OBJECTIVE: Phlebolymphedema (chronic venous insufficiency-related lymphedema) is a common and costly condition. Nevertheless, there is a dearth of evidence comparing phlebolymphedema therapeutic interventions. This study sought to examine the medical resource utilization and phlebolymphedema-related cost associated with Flexitouch (FLX; Tactile Medical, Minneapolis, Minn) advanced pneumatic compression devices (APCDs) relative to conservative therapy (CONS) alone, simple pneumatic compression devices (SPCDs), and other APCDs in a representative U.S. population of phlebolymphedema patients. METHODS: This was a longitudinal matched case-control analysis of deidentified private insurance claims. The study used administrative claims data from Blue Health Intelligence for the complete years 2012 through 2016. Patients were continuously enrolled for at least 18 months, diagnosed with phlebolymphedema, and received at least one claim for CONS either alone or in addition to pneumatic compression (SPCDs or APCDs). The main outcomes included direct phlebolymphedema- and sequelae-related medical resource utilization and costs. RESULTS: After case matching, the study included 86 patients on CONS (87 on FLX), 34 on SPCDs (23 on FLX), and 69 on other APCDs (67 on FLX). Compared with CONS, FLX was associated with 69% lower per patient per year total phlebolymphedema- and sequelae-related costs net of any pneumatic compression device-related costs ($3839 vs $12,253; P = .001). This was driven by 59% fewer mean annual hospitalizations (0.13 vs 0.32; P < .001) corresponding to 82% lower inpatient costs and 55% lower outpatient hospital costs. FLX was also associated with 52% lower outpatient physical therapy and occupational therapy costs and 56% lower other outpatient-related costs. Compared with SPCDs, FLX was associated with 85% lower total costs ($1153 vs $7449; P = .008) driven by 93% lower inpatient costs ($297 vs $4215; P = .002), 84% lower outpatient hospital costs ($368 vs $2347; P = .020), and 85% lower other outpatient-related costs ($353 vs $2313; P = .023). Compared with APCDs, FLX was associated with 53% lower total costs ($3973 vs $8436; P = .032) because of lower outpatient costs and lower rates of cellulitis (22.4% vs 44.9% of patients; P = .02). CONCLUSIONS: This analysis indicates significant benefits attributable to FLX compared with alternative compression therapies that can help reduce the notable economic burden of phlebolymphedema.

US budget impact of increased payer adoption of the Flexitouch advanced pneumatic compression device in lymphedema patients with advanced chronic venous insufficiency and multiple infections.

AIMS: To assess the budget impact to a US commercial health plan of providing access to the Flexitouch (FLX) advanced pneumatic compression device (Tactile Medical) to lymphedema (LE) patients with either comorbid chronic venous insufficiency (CVI) or frequent infections. METHODS: Budget impact was calculated over 2 years for a hypothetical US payer with 10-million commercial members. Model inputs were derived from published sources and from a case-matched analysis of Blue Health Intelligence (BHI) claims data for the years 2012-2016. To calculate the budget impact, the Status Quo budget (i.e. total cost for LE and sequelae-related medical treatment) was compared to the budget under each of three Alternate Payer Policy scenarios which assumed that a sub-set of patients was redistributed from their initial treatment groups to a group that received FLX. Model outputs included cumulative payer costs, net budget impact, and breakeven point. Sensitivity analyses were performed to assess the impact of model inputs on results. RESULTS: Increasing access to FLX yielded a favorable budget impact in every scenario. For LE patients with comorbid CVI, the three alternate scenarios resulted in cumulative 2-year budget impacts of -$52,841, -$173,317, and -$375,601, respectively. For LE patients with comorbid frequent infections, the three alternate scenarios resulted in cumulative 2-year budget impacts of -$192,729, -$259,339, and -$613,179, respectively. LIMITATIONS: Use of claims data assumes accurate coding and does not allow one to control for disease severity or treatment adherence. Also, the distribution of patients between treatment arms was determined using claims data from a specific payer organization, and could differ for health plans with different coverage policies. CONCLUSIONS: While previous studies have illustrated cost savings with adoption of FLX, US commercial health plans may also achieve tangible cost savings by expanding access to FLX for LE patients with comorbid CVI and multiple infections.

Long-term natalizumab treatment is associated with sustained improvements in quality of life in patients with multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) patients experience lower health-related quality of life (HRQoL) than the general population. In clinical trials, natalizumab significantly improved HRQoL and reduced relapse rates and disability progression in patients with relapsing MS. In a 1-year analysis of patients included in the current study, HRQoL improvement occurred within 3 months of natalizumab initiation and continued for 1 year thereafter. However, natalizumab's long-term efficacy in improving HRQoL has not been studied. METHODS: In this longitudinal, observational, single-arm US study, HRQoL and treatment satisfaction were evaluated in MS patients receiving intravenous natalizumab 300 mg every 4 weeks in clinical settings. Patients completed surveys at baseline and every 6 months for 3 years and reported the following measures: Short Form-12 Version 2 (SF-12v2), Multiple Sclerosis Impact Scale (MSIS-29), and Treatment Satisfaction Questionnaire for Medication. RESULTS: In this study, 120 patients completed ≥3 years of natalizumab treatment. Significant HRQoL improvements were evident from baseline to year 3 by increases in SF-12v2 Physical Component Summary (PCS) and Mental Component Summary scores (P<0.01) and decreases in MSIS-29 physical and psychological scores (P<0.0001). Patients with less physical disability (baseline Disease Steps [DS] 0-2) had significant improvement from baseline to year 3 in SF-12v2 PCS (P<0.05) and MSIS-29 physical scores (P<0.05). Physical HRQoL outcomes in patients with baseline DS 3-6 remained stable over 3 years. Treatment satisfaction increased significantly from baseline to year 1 (P<0.0001) and was maintained in the following 2 years. CONCLUSION: Patients reported physical and psychological HRQoL improvements over 3 years of natalizumab treatment, supporting the long-term efficacy of natalizumab in real-world settings. Lower baseline disease activity and earlier treatment were related to better outcomes, indicating the importance of starting natalizumab early in the disease course. Treatment satisfaction increased after natalizumab initiation and remained high over 3 years of treatment.

Informal Care Time and Cost in a Large Clinical Trial Sample of Patients with Mild to Moderate Alzheimer's Disease: Determinants and Level of Change Observed.

INTRODUCTION: We evaluate the association between caregiver (informal) time/cost and illness severity from two recently completed clinical trials of an investigational drug for Alzheimer's disease (AD). METHODS: Changes from baseline caregiver time were calculated and treatment effects analyzed using a restricted maximum likelihood-based mixed model for repeated measures. Four separate models were then estimated to examine the association between caregiver time costs and the clinical endpoints measured during the trials, including cognition (MMSE), function (DAD), behavior (NPI), global disability (CDR) and dependence (DS). RESULTS: Caregiver time cost was significantly associated with all clinical measures of illness severity with a 1-unit change in MMSE, DAD, NPI, CDR and DS associated with a 11.57%, 4.81-4.97%, 3.58-3.67%, 42.52% and 71.05% change, respectively, in primary caregiver time cost. The association between caregiver time cost and DS was the strongest of all the associations examined. CONCLUSION: Caregiver time costs increase with increasing AD severity in all key domains of AD (cognition, function, behavior, global disability and dependence on others). Our analysis demonstrated that patient dependence is a particularly important predictor of caregiver time costs and should be considered as a potential outcome measure in intervention clinical trials in AD. FUNDING: Pfizer Inc. and Janssen Alzheimer Immunotherapy Research and Development.

The High Direct Medical Costs of Prader-Willi Syndrome.

OBJECTIVE: To assess medical resource utilization associated with Prader-Willi syndrome (PWS) in the US, hypothesized to be greater relative to a matched control group without PWS. STUDY DESIGN: We used a retrospective case-matched control design and longitudinal US administrative claims data (MarketScan) during a 5-year enrollment period (2009-2014). Patients with PWS were identified by Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code 759.81. Controls were matched on age, sex, and payer type. Outcomes included total, outpatient, inpatient and prescription costs. RESULTS: After matching and application of inclusion/exclusion criteria, we identified 2030 patients with PWS (1161 commercial, 38 Medicare supplemental, and 831 Medicaid). Commercially insured patients with PWS (median age 10 years) had 8.8-times greater total annual direct medical costs than their counterparts without PWS (median age 10 years: median costs $14 907 vs $819; P < .0001; mean costs: $28 712 vs $3246). Outpatient care comprised the largest portion of medical resource utilization for enrollees with and without PWS (median $5605 vs $675; P < .0001; mean $11 032 vs $1804), followed by mean annual inpatient and medication costs, which were $10 879 vs $1015 (P < .001) and $6801 vs $428 (P < .001), respectively. Total annual direct medical costs were ∼42% greater for Medicaid-insured patients with PWS than their commercially insured counterparts, an increase partly explained by claims for Medicaid Waiver day and residential habilitation. CONCLUSION: Direct medical resource utilization was considerably greater among patients with PWS than members without the condition. This study provides a first step toward quantifying the financial burden of PWS posed to individuals, families, and society.

Dependence in Alzheimer's disease and service use costs, quality of life, and caregiver burden: the DADE study.

BACKGROUND: Most models determining how patient and caregiver characteristics and costs change with Alzheimer's disease (AD) progression focus on one aspect, for example, cognition. AD is inadequately defined by a single domain; tracking progression by focusing on a single aspect may mean other important aspects are insufficiently addressed. Dependence has been proposed as a better marker for following disease progression. METHODS: This was a cross-sectional observational study (18 UK sites). Two hundred forty-nine community or institutionalized patients, with possible/probable AD, Mini-Mental State Examination (3-26), and a knowledgeable informant participated. RESULTS: Significant associations noted between dependence (Dependence Scale [DS]) and clinical measures of severity (cognition, function, and behavior). Bivariate and multivariate models demonstrated significant associations between DS and service use cost, patient quality of life, and caregiver perceived burden. CONCLUSION: The construct of dependence may help to translate the combined impact of changes in cognition, function, and behavior into a more readily interpretable form. The DS is useful for assessing patients with AD in clinical trials/research.

Cognition in MCI and Alzheimer's disease: baseline data from a longitudinal study of the NTB.

Baseline data are summarized from a study examining the psychometric properties of the Neuropsychological Test Battery (NTB) and its subtests, and correlating the NTB with other cognitive and functional assessments. A multicenter, longitudinal, non-interventional study included mild to moderate Alzheimer's disease (AD, n = 196), mild cognitive impairment (MCI, n = 70), or normal cognition participants (NC, n = 75). The NTB, other cognitive assessment tools, functional/behavioral questionnaires, and health outcome assessments were administered. At baseline composite NTB, NTB memory, and NTB executive function z-scores were significantly lower for participants with AD compared with MCI, and for participants with MCI compared with NC. The composite NTB z-score had high test-retest reliability between screening and baseline. The results of this study suggest that NTB exhibits good reliability in patients with mild to moderate AD and MCI.

Health-related quality of life during natalizumab maintenance therapy for Crohn's disease.

OBJECTIVES: We evaluated the effects of treatment on health-related quality of life (HRQoL) during a randomized controlled trial of natalizumab maintenance therapy (ENACT-2) using both disease-specific and generic measures. METHODS: Crohn's disease patients who received natalizumab as induction therapy in ENACT-1 (N=724) and responded (N=339) were re-randomized to ENACT-2 in which they received natalizumab 300 mg (N=168) or placebo (N=171) every 4 wk for 48 additional wk. Outcome measures were the change from baseline on the inflammatory bowel disease questionnaire (IBDQ), the short form-36 (SF-36), the EuroQol-5D (EQ-5D), and a subject global assessment. RESULTS: At entry into ENACT-1, scores indicated substantially impaired HRQoL for both the disease-specific and general measures. Natalizumab responders showed clinically meaningful improvement in HRQoL over the course of the ENACT-1 study. During maintenance therapy, IBDQ and SF-36 scale scores of patients who responded to natalizumab induction and were re-randomized to receive the drug in ENACT-2 (N=168) remained stable, while those re-randomized to placebo (N=171) worsened. At week 60, 48 wk after the initiation of maintenance therapy, the mean change from ENACT-1 baseline of all scales of the IBDQ and the SF-36 was significantly higher for those who continued to receive natalizumab (P<0.001 for all scales). The scores of patients who received maintenance natalizumab treatment were not statistically different from those of a cross-section of the U.S. population for 6 of 8 scales of the SF-36. CONCLUSIONS: The substantial improvement in HRQoL experienced by patients who responded to natalizumab induction therapy was maintained during an additional 48 wk of maintenance therapy.

Mapping from disease-specific measures to utility: an analysis of the relationships between the Inflammatory Bowel Disease Questionnaire and Crohn's Disease Activity Index in Crohn's disease and measures of utility.

OBJECTIVES: To examine the relationship between the Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn's Disease Activity Index (CDAI) and measures of utility (EQ-5D and the SF-6D indexes), and to estimate algorithms to map the two utility values from IBDQ and CDAI scores. METHODS: A large data set from clinical trials in Crohn's disease provided contemporaneous patient responses to all four questionnaires. Paired observations from multiple time-points were analyzed. We calculated mean utility scores by IBDQ and CDAI score deciles; Spearman correlation coefficients for paired observations between IBDQ and EQ-5D (n = 3320) and IBDQ and SF-6D (n = 3230), and explored regression models using maximum likelihood estimation. The IBDQ/SF-6D model was validated against paired observations from an independent data set. RESULTS: The IBDQ decile analysis demonstrated a consistent positive relationship with both utility indexes. Correlations between the IBDQ and both the EQ-5D and SF-6D were statistically significant (P < 0.0001), with correlation coefficients of 0.76 and 0.85, respectively. A simple linear model between EQ-5D and IBDQ explained 45% of the variance. The residuals plot for the IBDQ/SF-6D model suggested some nonlinearity and a nonlinear model explained 69% of the variance. In the validation analysis, no statistically significant difference was observed between the mean observed SF-6D and the SF-6D scores estimated using the IBDQ/SF-6D regression model. CONCLUSIONS: Given the strength, consistency, and predictable characteristics of the relationships, the algorithms appear to provide valuable and valid methods to estimate utilities from IBDQ scores (but not CDAI) in trials of Crohn's disease patients that have collected IBDQ scores but not utilities.