Impact of adherence to antidepressants on healthcare outcomes and costs among patients with type 2 diabetes and comorbid major depressive disorder

Objective: To evaluate the association between adherence to antidepressants and an effect on clinical outcomes and healthcare costs in patients with major depressive disorder (MDD) and comorbid type 2 diabetes (T2D).

Methods: This retrospective study used MarketScan claims data from January 2012 to March 2014. Study entry was the first claim for an antidepressant and a diagnosis code for MDD and T2D in the prior 6 months. Adherence and persistence with antidepressant therapy in the first 180 days were defined as medication possession ratio (MPR)?≥?80% and length of therapy (LOT), with no treatment gap of >15 days, respectively. T2D control (HbA1c <7%), oral diabetes medication adherence, and healthcare costs were measured in the 12 month post-index period. The impact of antidepressant adherence and persistence on outcomes was assessed using multivariable analyses.

Results: Among the 1361 patients included, the mean age was 59 years and 55% were women. About one-third of the patients were adherent (35.9%, mean MPR?=?40%), persistent (32.0%, average LOT?=?100 days), and adherent/persistent (31.2%) on antidepressants. Being adherent, persistent, or adherent/persistent to antidepressants was associated with a two-fold improvement in adherence to oral diabetes medications. Of those with HbA1c data (n?=?121), adherence or adherence/persistence to antidepressants was associated with patients being five times more likely to have T2D control (odds ratio [OR]: 4.95; 95% confidence interval [CI]: 1.39, 17.59, p?=?.0134). Comparison between antidepressant-persistent and non-persistent patients was not significant. Mean difference in adjusted all-cause annual costs showed lower costs among antidepressant-adherent and adherent/persistent patients (adherent: -$350, 95% CI: -$462, -$247; adherent/persistent: -$1165; 95% CI: -$1280, -$1060).

Conclusions: Patients with better antidepressant adherence and adherence/persistence demonstrated better HbA1c control, with lower all-cause total and medical costs. Adherence, persistence, or adherence/persistence to antidepressants was associated with improved adherence to oral diabetes medications.     

The economic implications of the racial and ethnic disparities in the use of selective serotonin reuptake inhibitors*

ABSTRACT

Objectives: Previous studies have examined racial and ethnic disparities in the use of selective serotonin reuptake inhibitors (SSRI). This study aims to examine the economic implications of these disparities.

Research design and methods: In this retrospective observational study, the study sample was adult survey respondents with a diagnosis of depression from the Medical Expenditure Panel Survey (2002–2003). SSRI use was measured as the number of times when SSRIs were obtained. The racial and ethnic disparities in SSRI use were examined employing a negative binomial model. The economic implications of disparities were explored using a linear regression with SSRI use as an independent variable. Interaction terms between the variable for SSRI use and dummy variables for racial and ethnic groups were included to explore whether the relationships between SSRI use and health expenditures differ across racial and ethnic groups.

Results: The mean number of times of SSRI use was higher for non-Hispanic whites than non-Hispanic blacks (3.02 vs. 1.79; p < 0.05) and Hispanic whites (3.02 vs. 1.68; p < 0.05). These differences were still significant after adjusting for covariates (?p < 0.05). In the multivariate analysis, each time of SSRI use was associated with health expenditures of $301 higher. Neither dummy variables for racial and ethnic groups nor the interaction terms between these dummy variables and the variable for SSRI use were significant.

Conclusions: The lower use of SSRIs among minorities compared to non-Hispanic whites is associated with lower health expenditures among minorities. SSRI may be a proxy for improved access to health care due to under-treatment of depression in general. The main limitation of this study is that its observational nature does not allow the researchers to determine whether the association between SSRI use and the increase in health expenditures is a causal effect.     

Racial and ethnic disparities associated with the measure for drug-drug interactions among Medicare beneficiaries

BackgroundDrug-drug interactions (DDIs) cause many preventable hospitalizations and admissions. Efforts have been made to raise DDI awareness and reduce DDI occurrence; for example, Medicare Part D Star Ratings, a health plan quality assessment program, included a DDI measure. Previous research reported racial and ethnic disparities in health services utilization and that racial and ethnic minorities, compared with non-Hispanic whites (whites), may be less likely to be targeted for a similar measure, a Star Ratings adherence measure for diabetes medications.ObjectiveThis study aimed to investigate whether any racial and ethnic disparities are associated with the DDI measure in Part D Star Ratings among Medicare populations with diabetes, hypertension, and hyperlipidemia.MethodsThis cross-sectional study analyzed a 2017 Medicare Part D data sample, including 3,960,813 beneficiaries. Because the inclusion in the denominator of the Star Ratings DDI measure was determined by the use of a list of target medications, the likelihood of using a listed target medication was compared between racial and ethnic minorities and whites. Individuals with diabetes, hypertension, and hyperlipidemia were included in the analysis owing to the high prevalence of these conditions. Patient- and community-level characteristics were adjusted by logistic regression.ResultsOf the entire study sample, 26.2% used a target medication. Compared with whites, most racial and ethnic minorities were less likely to use a target medication. For example, among individuals with diabetes, blacks, Hispanics, Asians/Pacific Islanders, and others had, respectively, 14% (odds ratio 0.86 [95% CI 0.84–0.88]), 5% (0.95 [0.93–0.98]), 12% (0.88 [0.84–0.92]), and 10% (0.90 [0.87–0.93]) lower odds compared with whites. Findings were similar among hypertension and hyperlipidemia cohorts, except that Hispanics had similar odds of use as whites.ConclusionMost racial and ethnic minorities may have lower likelihood of being targeted for the DDI measure compared with whites. Future studies should examine whether these disparities affect health outcomes and devise new DDI measures for racial and ethnic minorities.     

The effect of fixed combination of fluticasone and salmeterol on asthma drug utilization,asthma drug cost,and episodes of asthma exacerbations

ABSTRACT

Objective: This study evaluated the use and drug costs of inhaled corticosteroids (ICSs), long-acting β₂-agonists (LABAs), and fluticasone propionate and salmeterol in a fixed-dose combination (FSC) and their relationship to asthma exacerbations before and after the market introduction of FSC in April 2001.

Methods: This is a retrospective analysis of employer-sponsored health insurance claims filed between January 1, 1998, and December 31, 2003 to detect impact of introduction of FSC (approved by the US Food and Drug Administration in August 2000) on utilization and cost of FSC, any ICS (excluding FSC), and any LABA (excluding FSC) along with utilization of medical services related to asthma exacerbations. Asthma medications were identified using National Drug Codes and Redbook, whereas asthma exacerbations were identified using ICD?9?CM primary diagnosis code 493.x. These medical and pharmacy claims were converted to rates per 100 asthma office visits.

Results: For all ICSs, the average pharmacy claims per 100 office visits increased from 383 in the year before FSC was introduced to 407 (120 [29.5%] were for FSC and 287 [70.5%] were for single-entity ICSs) in 2003. LABA prescribing increased from 72 in the year before FSC to 147 (120 from FSC, 27 single-entity LABA) in 2003 (?p < 0.001). An additional $13?511 per 100 asthma office visits was spent on the FSC product (?p < 0.001). After the introduction of FSC, there was no significant difference in asthma admissions (?p = 0.17), whereas emergency department (ED) visits increased by 0.92 visits per 100 office visits (?p = 0.03). The diagnosis and severity of asthma was inferred from the pharmacy claims and patients with chronic obstructive pulmonary disease could not be excluded. In addition, the study was not designed to assess the impact of other asthma medications on the disease and/or associated costs, and patient adherence to claimed medication could not be monitored.

Conclusions: The introduction of FSC was associated with increased LABAs/FSC patient exposure and expenditure with no change in asthma hospitalizations and an increase in ED visits.     

Historical trend of racial and ethnic disparities in meeting Medicare medication therapy management eligibility in non-Medicare population

BackgroundPrior research examining racial and ethnic disparities in meeting Medicare medication therapy management (MTM) eligibility criteria among the non-Medicare population suggests minorities have lower likelihood of being eligible than non-Hispanic Whites (Whites). However, such research has not examined trends in disparities and whether these disparities may be expected to decrease over time based on historical data.ObjectivesTo examine trends in MTM eligibility disparities among the non-Medicare population from 1996–1997 to 2009–2010.MethodsThis retrospective observational analysis used Medical Expenditure Panel Survey data from the two study periods. The MTM eligibility criteria used by health insurance plans in 2008 and 2010 were analyzed. Trends in disparities were examined by including interaction terms between dummy variables for 2009–2010 and non-Hispanic Blacks (Blacks)/Hispanics in a logistic regression. Interaction effects were estimated on both the multiplicative and additive terms. Main and sensitivity analyses were conducted to represent the ranges of the Medicare MTM eligibility thresholds used by health insurance plans.ResultsAccording to the main analysis, Blacks and Hispanics were less likely to be eligible than Whites for both sets of eligibility criteria in 1996–1997 and in 2009–2010. Trend analysis for both sets of criteria found that on the multiplicative term, there were generally no significant changes in disparities between Whites and Blacks/Hispanics from 1996–1997 to 2009–2010. Interaction on the additive term found evidence that disparities between Whites and Blacks/Hispanics may have increased from 1996–1997 to 2009–2010 (e.g., in the main analysis between Whites and Hispanics for 2010 eligibility criteria: difference in odds = −0.03, 95% CI: [−0.03]–[−0.02]).ConclusionsRacial and ethnic minorities in the non-Medicare population experience persistent and often increasing disparities in meeting MTM eligibility criteria. Drug benefit plans should take caution when using elements of Medicare MTM eligibility criteria.     

Adherence to iron chelation therapy in patients who switched from deferasirox dispersible tablets to deferasirox film-coated tablets

Objective: To compare real-world adherence to and persistence with deferasirox film-coated tablets (DFX-FCT) and deferasirox dispersible tablets (DFX-DT) among patients who switched from DFX-DT to DFX-FCT, overall and by disease type (sickle cell disease [SCD], thalassemia, and myelodysplastic syndrome [MDS]).

Methods: Patients were ≥2 years old and had ≥2 DFX-FCT claims over the study period and ≥2 DFX-DT claims before the index date (first DFX-FCT claim). The DFX-DT period was defined from the first DFX-DT claim to the index date; the DFX-FCT period was defined from the index date to the end of the study period. Adherence was measured as medication possession ratio (MPR) and proportion of days covered (PDC). Persistence was defined as continuous medication use without a gap ≥30 or 60 days between refills. Comparisons were conducted using paired-sample Wilcoxon sign-rank and McNemar’s tests.

Results: In total, 606 patients were selected (SCD: 348; thalassemia: 107; MDS: 106; other: 45). Adherence and persistence in the DFX-FCT vs DFX-DT period was significantly higher across all measures: mean MPR was 0.80 vs 0.76 (p?<?.001); 60.9% vs 54.3% of patients had MPR?≥?0.8 (p?=?.009); mean 3-month PDC was 0.83 vs 0.71 (p?<?.001); 64.2% vs 45.4% of patients had 3-month PDC?≥?0.8 (p?<?.001); 87.2% vs 63.4% of patients had 3-month persistence with no gap ≥30 days and 96.1% vs 79.9% with no gap ≥60 days (p?<?.001). Adherence and persistence improved after switching across all diseases, particularly MDS.

Conclusions: Adherence and persistence improved significantly after switching from DFX-DT to DFX-FCT for all diseases, but especially MDS.     

Association between availability of care providers and healthcare utilizations among adults with asthma

Background: Limited accessibility to providers may delay appropriate control of asthma exacerbations. The objective of our study is to estimate the contributors to the hospital/emergency department (ED) visits among adults with asthma focusing on the availability of healthcare providers.

Methods: We conducted a pooled cross-sectional analysis using the 2011–2013 Asthma Call-Back Survey linked with 2012–2016 Area Health Resource Files. We employed multivariable logistic regression with dichotomous outcomes of hospitalization and ED visits. Key covariates were the availability of county-level healthcare provider variables per 100,000 persons such as the number of lung disease specialists (including pulmonary care specialists, and allergy and immunology specialists), the number of hospitals, the number of safety-net facilities including rural health centers (RHCs) and federally qualified health centers (FQHCs), and the number of primary care physicians (PCPs).

Results: Among 25,621 adults, proportions of hospital visits and ED visits were 3.3% and 13.2%, respectively. An additional RHC reduced by 3% the odds of having an ED visit (odds ratio [OR]?=?0.97, p?=?.004). Patients with cost barriers to seeing a PCP were 60% (OR?=?1.60, p?=?.028) more likely to have a hospital visit than those without. In addition, patients with cost barriers to seeing a specialist were 90% (OR?=?1.90, p?=?.007) and 111% (OR?=?2.11, p?=?.001) more likely to have a hospital visit and ED visit, respectively, than those without.

Conclusions: Hospital and ED visits among adults with asthma are partially related to the availability of providers, and more related to financial barriers. Therefore, financial support for the vulnerable asthma population might be a target for policy makers interested in reducing hospitalizations and ED visits.     

An update on the safety of long-acting β-agonists in asthma patients using inhaled corticosteroids

Importance of the field: Pooled trial data have shown that long-acting β-agonists increase the risk for asthma hospitalizations and deaths by two to fourfold compared with placebo. Until recently, it was unclear whether concomitant inhaled corticosteroids (ICSs) could eliminate this risk.

Areas covered in this review: This review summarizes the available data on the safety of long-acting β-agonist use in asthma, with and without concomitant ICSs. The results from an updated meta-analysis are presented, with data through December 2008.

What the reader will gain: In pooled trial data, catastrophic asthma events (defined as asthma-related intubation or death) were increased fourfold for concomitant treatment with long-acting β-agonists and ICSs compared with corticosteroids alone (odds ratio 3.7; 95% CI 1.4 – 9.6). It is estimated that the addition of long-acting β-agonists to ICS therapy is associated with an absolute increase of one catastrophic event per 1500 patient-years.

Take home message: When the available trial data are pooled together, it is clear that long-acting β-agonists significantly increase the risk for asthma-related intubations and deaths, even when used in a controlled fashion with concomitant ICSs. Clinical guidelines should readdress the role long-acting β-agonists have in the management of asthma.     

Ciclesonide and the treatment of asthma

Importance of the field: Asthma is a chronic disease characterized by airway inflammation and hyper-responsiveness. Inhaled corticosteroids (ICSs) constitute the guideline-recommended first-line therapy for persistent asthma. However, concerns regarding ICS-related adverse events may contribute to their underutilization by physicians and patients.

Areas covered in this review: The currently available published data on the pharmacokinetic and pharmacodynamic properties, safety and efficacy of the ICS, ciclesonide, is described. Peer-reviewed publications (1996 – 2009) on the pharmacodynamic and pharmacokinetic profile, safety and efficacy of ciclesonide were reviewed.

What the reader will gain: Ciclesonide is delivered as an inactive prodrug, which is cleaved to the active molecule by intracellular esterases located in the lungs. This and other pharmacodynamic and pharmacokinetic properties may limit the amount of active molecule outside the lung and may reduce the incidence of side effects. Randomized placebo-controlled studies found that ciclesonide can initiate and maintain disease control in subjects with persistent asthma of all disease severities. Moreover, studies have found that ciclesonide is as effective as other ICSs in establishing and controlling disease symptoms. Controlled clinical trials also showed that ciclesonide is associated with minimal systemic and local treatment-related adverse events.

Take home message: Published findings indicate that ciclesonide is effective at initiating and maintaining asthma control and is well tolerated, with a positive safety profile.     

Mometasone furoate dry powder inhaler: a once-daily inhaled corticosteroid for the treatment of persistent asthma

ABSTRACT

Background: Mometasone furoate (MF), a potent synthetic inhaled corticosteroid (ICS) with a high affinity for the glucocorticoid receptor, is approved for use in the treatment of asthma.

Scope: Publications reviewed in this article were identified via searches of MEDLINE and EMBASE databases using the terms ‘mometasone furoate AND pharmacology’ and ‘mometasone furoate AND asthma AND clinical trial’. Data from abstracts presented at respiratory society meetings, and relevant background information, are also reviewed.

Findings: In clinical studies, MF, administered by dry powder inhaler (MF-DPI), was effective in treating all severities of persistent asthma, improving pulmonary function, reducing asthma symptoms, and reducing or eliminating the need for oral corticosteroids. Once-daily dosing of MF-DPI was effective in patients with mild or moderate persistent asthma previously taking twice-daily regimens of inhaled corticosteroids (ICSs), and in patients taking only inhaled β₂?agonists for symptom relief. Once-daily dosing in the evening with MF-DPI 200?µg conferred a greater benefit than morning dosing with MF-DPI 200?µg. Patients with severe asthma who were dependent on oral corticosteroids (OCSs) and high doses of ICSs were able to achieve greater asthma control and reduce or even eliminate OCSs when switched to MF-DPI. In trials of up to 1 year in duration, MF-DPI was well tolerated, with the majority of adverse events considered mild or moderate in intensity. MF had low systemic bioavailability and no clinically significant hypothalamic–pituitary–adrenal-axis suppression at therapeutic doses. The DPI device is a multiple-dose inhaler with a counter containing agglomerates of MF and lactose. Patients of all severities of persistent asthma were able to generate and maintain airflow profiles necessary to provide a uniform and accurate dose.

Limitations: Only one study evaluated both morning and evening administration of once-daily doses, and one of the comparative clinical trials was an open-label study.

Conclusion: Once-daily administration of MF-DPI 200–400?µg in patients with mild to moderate persistent asthma effectively improved lung function and asthma control. In patients with severe persistent asthma dependent on oral corticosteroids, treatment with MF-DPI 400?µg BID permitted substantial reduction of oral corticosteroid use. All MF-DPI treatments were well tolerated and had minimal systemic effects.     

Inhaled corticosteroids for chronic obstructive pulmonary disease

Introduction: Current guidelines recommend the use of inhaled long-acting bronchodilators, inhaled corticosteroids (ICSs) and their combinations for maintenance treatment of moderate-to-severe chronic obstructive pulmonary disease (COPD); however, it is questionable whether all COPD patients should be treated, as the long-term use of ICSs is accompanied by side effects.

Areas covered: This article reviews the evidence about the effects of ICSs in the treatment of COPD. It mainly focuses on meta-analyses of published data and pooled analyses of primary data. It also offers an overview of pipeline developments.

Expert opinion: There is now more evidence that there are subsets of patients (mainly, frequent exacerbators with predominant chronic bronchitis and those with overlap between COPD and asthma) with a favorable response to treatment with ICSs (i.e., reduced progression of lung function loss, reduced exacerbation rate and improved health-related quality of life). Therefore, nowadays, the right question is not whether ICSs should not be used at all unless patients have concomitant asthma, but, instead, which COPD patient can benefit from a therapy with ICSs. Unfortunately, however, the number of studies that have investigated the clinical features that might predict corticosteroid response in COPD is still inadequate.     

Association of waterpipe smoking with myocardial infarction and determinants of metabolic syndrome among catheterized patients

Background: Waterpipe smoking is a rising global public health epidemic perceived by many users to be less harmful, though its toxicity overlaps or even exceeds that of cigarette smoking. Short-term cardiovascular changes due to waterpipe smoking are well established, but longer-term health impacts are still not fully elucidated.

Objective: We aim to investigate the association of waterpipe smoking with myocardial infarction among patients undergoing cardiac catheterization.

Methods: The study was performed on Lebanese patients referred for cardiac catheterization. Patient’s blood was collected for metabolic measures and questionnaires were filled out to include socio-demographic, behavioral and pertinent medical characteristics of the study subjects.

Results: Myocardial infarction is significantly and independently associated with waterpipe smoking, with odds ratio (OR) of 1.329 (95% CI: [1.04–1.68]; p?=?.021), which is lower than that for cigarette smoking (OR?=?1.87, 95% CI: [1.63–2.15]; p?p?=?.032).

Conclusion: The study provides yet another evidence for the adverse cardiovascular effects of waterpipe smoking on a clinical level. The harmful effects of waterpipe smoking should be underscored by health care professionals.     

Real-world adherence assessment of lurasidone and other oral atypical antipsychotics among patients with schizophrenia: an administrative claims analysis

Objective: To compare adherence with lurasidone to other oral atypical antipsychotics among Medicaid and commercially insured patients with schizophrenia.

Research design and methods: Administrative claims of patients with schizophrenia treated with atypical antipsychotics (lurasidone, aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone) from October 2010 to September 2011 were identified from MarketScan Commercial and Medicaid Databases, and were classified by the first (index) antipsychotic. Patients were 18–64 years, had insurance coverage 12 months pre- and 6 months post-index, and no pre-index use of the index drug.

Main outcome measures: Medication possession ratio (MPR), discontinuation rate, and mean time to discontinuation were assessed post-index. Pairwise comparisons (lurasidone versus each drug) were conducted using chi-square tests and Student’s t-tests.

Results: There were 146 Medicaid (mean age 43.5 years, 47.9% female) and 63 commercial (mean age 40.0 years, 42.9% female) patients treated with lurasidone. In the Medicaid population, the MPR for patients treated with lurasidone was 0.60, versus 0.41–0.48 for patients treated with other antipsychotics (all p?p?p?p?p?Conclusions: In Medicaid and commercial populations, patients treated with lurasidone demonstrated greater adherence compared to patients treated with other atypical antipsychotics. Limitations of using administrative claims data include potential errors or inconsistencies in coding, and lack of complete clinical information.     

Sex differences in the relationships between childhood adversity,attachment anxiety and current smoking

Background: Smoking behavior and smoking cessation are complex. Interpersonal factors such as childhood adversity are associated with smoking, especially in women. Identifying how and in whom these individual factors contribute to smoking behavior may support individualized smoking cessation strategies. Attachment insecurity (attachment avoidance and attachment anxiety) involves biological and psychological processes in close relationships and is associated with both childhood adversity, and in select populations, smoking. This study aims to identify an association between attachment insecurity and smoking in adults and to determine if attachment insecurity is a plausible mediator between childhood adversity and smoking.

Methods: In a cross-sectional survey, 348 primary care patients reported childhood adversity, attachment insecurity and smoking status. Statistical analyses were performed using regression and PRODCLIN.

Results: Sixty-one percent of participants had experienced childhood adversity and 20% were current smokers. In women, attachment anxiety was associated with both childhood adversity (p?=?.002) and current smoking (p?=?.04). The PRODCLIN test indicated that attachment anxiety may be a mediator between childhood adversity and current smoking in women (95%CI 0.003, 0.236). In men, current smoking was not associated with childhood adversity (p?=?.673) or attachment anxiety (p?=?.29). Attachment avoidance was not related to current smoking in men (p?=?.31) or in women (p?=?.16).

Conclusions: In women but not in men, attachment anxiety is associated with current smoking and may mediate the relationship between childhood adversity and current smoking. Childhood adversity and attachment anxiety may be factors to consider in the design of cessation strategies for women.     

A cross-sectional study of changes in markers of immunological effects and lung health due to exposure to multi-walled carbon nanotubes

Background: Multi-wall carbon nanotubes (MWCNTs) are manufactured nanomaterials to which workers and the general population will be increasingly exposed in coming years. Little is known about potential human health effects of exposure to MWCNTs, but effects on the lung and the immune system have been reported in animal and mechanistic studies.

Objectives: We conducted a cross-sectional study to assess the association between occupational exposure to MWCNTs and effects on lung health and the immune system.

Methods: We assessed 51 immune markers and three pneumoproteins in serum, complete blood cell counts (CBC), fractional exhaled nitric oxide (FENO), and lung function among 22 workers of a MWCNT producing facility and 39 age- and gender-matched, unexposed controls. Measurements were repeated four months later among 16 workers also included in the first phase of the study. Regression analyses were adjusted for potentially confounding parameters age, body mass index, smoking, and sex, and we explored potential confounding by other factors in sensitivity analyses.

Results: We observed significant upward trends for immune markers C-C motif ligand 20 (p?=?.005), basic fibroblast growth factor (p?=?.05), and soluble IL-1 receptor II (p?=?.0004) with increasing exposure to MWCNT. These effects were replicated in the second phase of the study and were robust to sensitivity analyses. We also observed differences in FENO and several CBC parameters between exposed and non-exposed, but no difference in lung function or the pneumoproteins.

Conclusions: We observed indications of early effects of occupational exposure to MWCNTs on lung health and the immune system.