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.

Real-world assessment of the relationship between migraine-related disability and healthcare costs in the United States.

OBJECTIVE: The objective of this study was to determine the associations among migraine disability assessment scores, healthcare resource utilization (HCRU; medical visits and pharmacy use) and direct medical costs among people with episodic migraine in a real-world setting. BACKGROUND: Migraine is a public health concern associated with a substantial economic burden in the United States. However, the association between migraine disability and direct medical costs among people with migraine is unknown. METHOD: This retrospective, cohort study used claims and electronic health record data from the Decision Resources Group database. Adults with migraine with or without aura, defined by International Classification of Disease Revision 9 (ICD-9) or ICD Revision 10 (ICD-10) codes, and a completed Migraine Disability Assessment Scale (MIDAS) questionnaire from January 2016 to December 2018 were included (chronic migraine codes not included). The associations of MIDAS score with the cost of HCRU for the 6 months after MIDAS assessment were explored. Results were stratified by treatment setting. RESULTS: Among 7662 included patients, MIDAS scores were distributed as: 3348 (43.7%; I, little/none), 1107 (14.4%; II, mild), 1225 (16.0%; III, moderate), 893 (11.7%; IVa, severe), and 1089 (14.2%; IVb, very severe). Worsening disability was associated with higher medical costs (adjusted from a multivariable model). In the primary care setting, healthcare visit costs were $206 (95% confidence interval: $144-294) for grade I and $631 ($384-1036) for grade IVb patients; corresponding pharmacy costs were $203 (grade I; $136-301) and $719 (grade IVb; $410-1259). For specialty care (e.g., neurologist), healthcare visits cost $509 ($411-629) for grade I and $885 ($634-1236) for grade IVb patients; corresponding pharmacy costs were $494 (grade I; $378-645) and $1020 (grade IVb; $643-1620). CONCLUSION: Higher levels of migraine-related disability (MIDAS assessed) are associated with increased HCRU costs among Americans with episodic migraine. Migraine disability assessment could be useful in the development, testing, and prescription of cost-effective treatments for people with high migraine-related disability.

Relationship Between Initial Parenteral Iron Therapy Dosing and Treatment Effectiveness: A Real-World Retrospective Analysis.

Purpose: Replacement iron is the main treatment for iron deficiency, but the relationship between initial intravenous (IV) dose and need for additional treatment is unclear. This study explored patterns of IV iron dosing in US clinical practice. Methods: Patient records were obtained for adults who received IV iron for anemia between 2015 and 2017. Patients were classified into four groups: those who received <1500 mg and ≥1500 mg IV iron and those received ≤1000 mg and >1000 mg within 3 weeks of their first dose. The proportion of patients requiring additional IV iron after 30 days of the initial dose was evaluated. Results: Data were obtained for 2959 patients receiving iron sucrose (44.2%), ferric carboxymaltose injection (FCM) (25.8%), and ferumoxytol (FM) (14.3%). Overall, 567 patients (19%) received ≥1500 mg of IV iron and 942 (32%) received >1000 mg of IV iron within the first 21 days. Mean (SD) baseline iron deficit was 1001 mg (312). Patients who received ≥1500 mg had a 32% lower probability of receiving additional IV iron than those who received <1500 mg (adjusted hazard ratio [HR]: 0.68 [95% confidence interval (CI); 0.58, 0.81]) and incurred significantly fewer outpatient visits for all causes (p < 0.001) and IV iron treatment (p < 0.001). Patients who received an initial dose of >1000 mg had a 41% lower probability of receiving additional IV iron than those who received ≤1000 mg (adjusted HR: 0.59 [95% CI; 0.52, 0.67]) and had significantly fewer outpatient visits for all causes (p < 0.001) and IV iron treatment (p < 0.001). Patients receiving FCM required fewer outpatient visits than those receiving FM and other treatments, including a subgroup of patients who initially received >1000 mg IV iron. Conclusion: Higher doses of IV iron within 3 weeks of first dose may reduce further IV iron treatment needs and outpatient visits.

Real-World Evidence of Treatment, Tolerance, Healthcare Utilization, and Costs Among Postacute Care Adult Patients Receiving Enteral Peptide-Based Diets in the United States.

OBJECTIVE: Peptide -based (PB) enteral tube feeding (ETF) formulas have been shown to reduce gastrointestinal (GI) intolerance in patients receiving enteral nutrition. However, limited data exist in relation to their use in the postacute/home care setting. We sought to assess the real-world GI tolerance, healthcare utilization, and resource use costs of 100% whey-protein PB ETF in adults in a postacute care setting and describe their demographic, clinical, and treatment characteristics. METHOD: Using medical claims data from the United States, we analyzed GI intolerance events occurring in adults receiving 100% whey-protein PB ETF (Peptamen® adult formulas) for one year before and after initiation of ETF. Resource use costs were subsequently estimated using a multivariate general linearized model and adjusted for age, gender, and Charlson Comorbidity Index score. RESULTS: The proportion of adults experiencing no GI intolerance events increased from 41% (418/1022) to 59% (601/1022) in the one-year period after initiation of 100% whey PB ETF (P < .001). The proportion of patients with at least one hospital inpatient visit also decreased from 100% (1022/1022) to 72% (737/1022) over the same period, and the mean number of inpatient visits per patient decreased from 15.6 to 13.0. Cost modeling revealed that outpatient visits accounted for 42% ($1174/$2820) of total estimated healthcare resource costs in the first 30 days after 100% whey PB ETF initiation, with only 9% ($255/$2820) due to emergency room visits. CONCLUSION: These 100% whey-protein PB ETF formulas are a valuable nutrition treatment option for patients with or at risk of malnutrition who show intolerance to standard ETF formulas and may reduce hospital inpatient visits and associated costs.

Antihypertensive agent utilization patterns among patients with uncontrolled hypertension in the United States.

Hypertension affects approximately one-third of the US adults. This study investigated antihypertensive utilization patterns among hypertensive patients who were prescribed treatment, yet still experienced uncontrolled hypertension. Data from the Decision Resources Group Real World Evidence Data Repository US database (2015-2016) were used to construct a cohort of uncontrolled hypertension patients to observe antihypertensive utilization patterns. Results for 5059 patients, with an average age of 57.8 (SD = 13.7), who had, on average 2.4 agents prescribed. Approximately half (51.9%) were female, and most were White (86.8%). More than one-third (N = 1877; 37.1%) of patients were diagnosed with diabetes mellitus (DM) or chronic kidney disease (CKD) that could independently contribute to increased cardiovascular complications. Overall, the most common treatments prescribed, as percent of agents and as percent of patients, respectively, were diuretics (24.9%; 59.6%), followed by angiotensin-converting enzyme inhibitors (ACEIs) (23.8%; 56.9%), beta-blockers (BBs) (18.7%; 44.8%), calcium channel blockers (CCBs) (15.4%; 36.8%), and angiotensin II receptor blockers (ARBs) (13.5%; 32.3%). Approximately one-tenth (10.5%) of the prescriptions were written for fixed-dose combination therapies. Among patients diagnosed with DM and CKD (N = 200), the order of the most common agents was the same as the overall cohort. Only 5.6% of prescriptions written for these patients were fixed-dose combination therapy. Based on clinical guidelines, which suggest using ACEIs, ARBs, or CCBs as first-line therapy, and fixed-dose combination therapy to increase adherence, this indicates over-prescribing of BBs and under-prescribing of fixed-dose combination therapy. These findings illustrate the need to further investigate challenges faced by patients and providers in treatment decision-making.

Importance of Initial Complete Parenteral Iron Repletion on Hemoglobin Level Normalization and Health Care Resource Utilization: A Retrospective Analysis.

STUDY OBJECTIVE: Iron deficiency anemia is the most common form of anemia, and parenteral iron therapy is necessary in select patients. The objective of this analysis was to assess the impact of initial complete parenteral iron repletion on serum hemoglobin (Hgb) level normalization and on health care resource utilization in real-world practice. DESIGN: Retrospective observational study. DATA SOURCE: Decision Resources Group Real-World Data Repository (United States databases). PATIENTS: A total of 2966 patients who had a baseline Hgb level below normal (< 12 g/dl for females and < 13.5 g/dl for males) and were treated with parenteral iron between March 2015 and February 2017. MEASUREMENTS AND MAIN RESULTS: The effect of receiving the required parenteral iron dose to replete the deficit, calculated by a modified Ganzoni formula, within 3 weeks of the first parenteral iron therapy claim (index date) on the likelihood of Hgb level normalization, was estimated by using logistic regression. All analyses were adjusted for sex, age, comorbidities, and use of prescription oral iron therapy. The adjusted mean numbers of all-cause inpatient admissions, outpatient visits, and emergency department (ED) visits within 6 months and 1 year after the index date were compared between patients with and without normalized Hgb levels by using negative binomial regression. Of the 2966 included patients, 33.9% received the required iron dose within 3 weeks of the index date, and 19.6%, 48.2%, and 53.9% had a normalized Hgb level within 8 weeks of the index date, within 1 year of the index date, and until the end of data availability, respectively. Patients who received the required iron dose within 3 weeks of the index date were significantly more likely to have a normalized Hgb level within 8 weeks of the index date and at any time during the study period than those who did not: adjusted odds ratio (OR) (95% confidence interval [CI]) 2.67 (2.20, 3.24) and 2.33 (1.96, 2.77), respectively. Hgb level normalization within 1 year of the index date was associated with fewer inpatient admissions and outpatient visits and a similar number of ED visits compared with no Hgb level normalization 1 year after the index date. CONCLUSION: The results of these analyses underscore the importance of initial complete parenteral iron repletion for rapidly improving clinical outcomes. Prompt achievement of a normalized Hgb level may also provide an opportunity to reduce health care resource utilization in patients with iron deficiency anemia receiving parenteral iron therapy.

Economic burden of disease-associated malnutrition in China.

Disease-associated malnutrition (DAM) is a well-recognized problem in many countries, but the extent of its burden on the Chinese population is unclear. This article reports the results of a burden-of-illness study on DAM in 15 diseases in China. Using data from the World Health Organization (WHO), the China Health and Nutrition Survey, and the published literature, mortality and disability-adjusted life years (DALYs) lost because of DAM were calculated; a financial value of this burden was calculated following WHO guidelines. DALYs lost annually to DAM in China varied across diseases, from a low of 2248 in malaria to a high of 1 315 276 in chronic obstructive pulmonary disease. The total burden was 6.1 million DALYs, for an economic burden of US$66 billion (Chinese ¥ 447 billion) annually. This burden is sufficiently large to warrant immediate attention from public health officials and medical providers, especially given that low-cost and effective interventions are available.

Effect of hospital use of oral nutritional supplementation on length of stay, hospital cost, and 30-day readmissions among Medicare patients with COPD.

BACKGROUND: COPD is a leading cause of death and disability in the United States. Patients with COPD are at a high risk of nutritional deficiency, which is associated with declines in respiratory function, lean body mass and strength, and immune function. Although oral nutritional supplementation (ONS) has been associated with improvements in some of these domains, the impact of hospital ONS on readmission risk, length of stay (LOS), and cost among hospitalized patients is unknown. METHODS: Using the Premier Research Database, we first identified Medicare patients aged ≥ 65 years hospitalized with a primary diagnosis of COPD. We then identified hospitalizations in which ONS was provided, and used propensity-score matching to compare LOS, hospitalization cost, and 30-day readmission rates in a one-to-one matched sample of ONS and non-ONS hospitalizations. To further address selection bias among patients prescribed ONS, we also used instrumental variables analysis to study the association of ONS with study outcomes. Model covariates included patient and provider characteristics and a time trend. RESULTS: Out of 10,322 ONS hospitalizations and 368,097 non-ONS hospitalizations, a one-to-one matched sample was created (N = 14,326). In unadjusted comparisons in the matched sample, ONS use was associated with longer LOS (8.7 days vs 6.9 days, P < .0001), higher hospitalization cost ($14,223 vs $9,340, P < .0001), and lower readmission rates (24.8% vs 26.6%, P = .0116). However, in instrumental variables analysis, ONS use was associated with a 1.9-day (21.5%) decrease in LOS, from 8.8 to 6.9 days (P < .01); a hospitalization cost reduction of $1,570 (12.5%), from $12,523 to $10,953 (P < .01); and a 13.1% decrease in probability of 30-day readmission, from 0.34 to 0.29 (P < .01). CONCLUSIONS: ONS may be associated with reduced LOS, hospitalization cost, and readmission risk in hospitalized Medicare patients with COPD.

Economic burden of community-based disease-associated malnutrition in the United States.

BACKGROUND: The burden imposed by disease-associated malnutrition (DAM) on patients and the healthcare system in food-abundant industrialized countries is often underappreciated. This study measured the economic burden of community-based DAM in the United States. METHODS: The burden of DAM was quantified in terms of direct medical costs, quality-adjusted life years lost, and mortality across 8 diseases (breast cancer, chronic obstructive pulmonary disease [COPD], colorectal cancer [CRC], coronary heart disease [CHD], dementia, depression, musculoskeletal disorders, and stroke). To estimate the total economic burden, the morbidity and mortality burden was monetized using a standard value of a life year and combined with direct medical costs of treating DAM. Disease-specific prevalence and malnutrition estimates were taken from the National Health Interview Survey and the National Health and Nutrition Examination Survey. Deaths by disease were taken from the Center for Disease Control and Prevention. Estimates of costs and morbidity were taken from the literature. RESULTS: The annual burden of DAM across the 8 diseases was $156.7 billion, or $508 per U.S. resident. Nearly 80% of this burden was derived from morbidity associated with DAM; around 16% derived from mortality and the remainder from direct medical costs of treating DAM. The total burden was highest in COPD and depression, while the burden per malnourished individual was highest in CRC and CHD. CONCLUSION: DAM exacts a large burden on American society. Therefore, improved diagnosis and management of community-based DAM to alleviate this burden are needed.

Impact of oral nutrition supplements on hospital outcomes in pediatric patients.

BACKGROUND: Nutrition deficiency is common among hospitalized children. Although oral nutrition supplements (ONS) may improve malnutrition in this population, the benefits and healthcare costs associated with their use have not yet been fully explored. The objective of this study was to assess the effect of ONS use on inpatient length of stay (LOS) and episode cost in hospitalized children. MATERIALS AND METHODS: Retrospective analysis of 557,348 hospitalizations of children aged 2-8 years in the Premier Research Database. The effect of ONS use on LOS and episode cost in a propensity score- matched sample was estimated in analyses with and without the use of instrumental variables (IVs) to reduce confounding from unobserved variables. RESULTS: ONS were prescribed in 6066 of 557,348 inpatient episodes (1.09%). In IV analysis, using a matched sample of 11,031 episodes, hospitalizations with ONS use had 14.8% shorter LOS (6.4 vs 7.5 days; 1.1 days [95% CI, 0.2-2.4]). Hospitalizations with ONS use had 9.7% lower cost ($16,552 vs $18,320; $1768 [95% CI, $1924-$1612]). CONCLUSIONS: ONS use was associated with lower LOS and episode cost among pediatric inpatients. ONS use in hospitalized pediatric patients may provide a cost-effective, evidence-based approach to improving pediatric hospital care.

Can Oral Nutritional Supplements Improve Medicare Patient Outcomes in the Hospital?

We analyzed the effect of oral nutritional supplement (ONS) use on 30-day readmission rates, length of stay (LOS), and episode costs in hospitalized Medicare patients (≥65), and subsets of patients diagnosed with acute myocardial infarction (AMI), congestive heart failure (CHF) or pneumonia (PNA). Propensity-score matching and instrumental variables were used to analyze ONS and non-ONS episodes from the Premier Research Database (2000-2010). ONS use was associated with reductions in probability of 30-day readmission by 12.0% in AMI and 10.1% in CHF. LOS decreases of 10.9% in AMI, 14.2% in CHF, and 8.5% in PNA were associated with ONS, as were decreases in episode costs in AMI, CHF and PNA of 5.1%, 7.8% and 10.6%, respectively. The effect on LOS and episode cost was greatest for the Any Diagnosis population, with decreases of 16.0% and 15.8%, respectively. ONS use in hospitalized Medicare patients ≥65 is associated with improved outcomes and decreased healthcare costs, and is therefore relevant to providers seeking an inexpensive, evidence-based approach for meeting Affordable Care Act quality targets.

Population pharmacokinetic and pharmacodynamic modeling for assessing risk of bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVE: We hypothesized that patients with bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) accumulate higher levels of BP in bone than those without BRONJ. STUDY DESIGN: Using the Pmetrics package and published data, we designed a population pharmacokinetic model of pamidronate concentration in plasma and bone and derived a toxic bone BP threshold of 0.2 mmol/L. With the model, and using patient individual BP duration and bone mineral content estimated from lean body weight, we calculated bone BP levels in 153 subjects. RESULTS: Mean bone BP in 69 BRONJ cases was higher than in 84 controls (0.20 vs 0.10 mmol/L, P < 0.001), consistent with the toxic bone threshold of 0.2 mmol/L. BRONJ was also associated with longer duration BP therapy (5.3 vs 2.7 years, P < 0.001), older age (76 vs 70 years, P < 0.001), and Asian race (49% vs 14%, P < 0.001). CONCLUSIONS: Our model accurately discriminated BRONJ cases from controls among patients on BP therapy.

Progestogen levels, progesterone receptor gene polymorphisms, and mammographic density changes: results from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study.

OBJECTIVE: Estrogen plus progestin therapy (EPT) in postmenopausal women increases breast cancer risk and mammographic density to a higher extent than does estrogen therapy alone. Data from the randomized placebo-controlled Postmenopausal Estrogen/Progestinv Interventions trial showed that EPT-induced increases in serum estrone and estrone sulfate levels were positively correlated with increases in mammographic density. Here, after adjusting for serum estrone and estrone sulfate levels, we investigated the roles of posttreatment serum progestogen increase and of progesterone receptor gene (PGR) genetic variations on changes in mammographic density. METHODS: We measured the percent mammographic density and serum progestogen levels in 280 Postmenopausal Estrogen/Progestin Interventions trial participants randomized to EPT treatment. Analyses of genetic variations in PGR were limited to 260 white women for whom we successfully obtained PGR genotypes. We used linear regression analyses to determine how an increase in progestogen levels and PGR genetic variation influenced mammographic density change after EPT. RESULTS: The increase in posttreatment serum progestogen level was positively associated with greater increases in mammographic density after adjustment for covariates (P trend = 0.044). Compared with women in the lowest quartile of serum progestogen level, women in the highest quartile experienced a 3.5% greater increase in mammographic density (P = 0.046). We did not find a strong indication that genetic variation in PGR was associated with mammographic density increase or modified the association with serum progestogen; however, confidence in these null findings is constrained by our small sample size. CONCLUSIONS: Our results suggest that higher serum progestogen levels resulting from EPT treatment lead to greater increases in mammographic density.