Factors associated with non-use and sub-target dosing of medical therapy for heart failure with reduced ejection fraction.

In clinical practice, many patients with heart failure with reduced ejection fraction (HFrEF) are either not prescribed guideline-directed medical therapies for which they are eligible or are prescribed therapies at sub-target doses. The objective of this study was to examine the factors associated with not receiving guideline-directed medical therapies or receiving sub-target doses. We conducted a systematic review of articles published between January 2014 and May 2019 that described dosing patterns and factors associated with non-use and sub-target dosing of HFrEF therapies in clinical practice. Thirty-seven studies were included. The percentages of patients reaching target doses for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, sacubitril/valsartan, beta-blockers, and mineralocorticoid receptor antagonists ranged from 4 to 55%, 11 to 87%, 4 to 60%, and 22 to 80%, respectively. Older age and worsening renal function were associated with non-use and sub-target dosing, lower body mass index was commonly associated with non-use, and hyperkalemia and hypotension were commonly associated with sub-target dosing. In conclusion, several common patient characteristics are associated with non-use and sub-target dosing of medical therapy for HFrEF. These high-risk groups are in particular need of further studies to improve implementation of available medications and to define the role of novel therapies.

Systematic literature review of the disease burden and vaccination of pneumococcal disease among adults in select Asia-Pacific areas.

INTRODUCTION: Pneumococcal diseases are common and cause significant morbidity and mortality, with higher rates especially in developing areas including many in the Asia-Pacific (AP) region. However, current strategies to prevent pneumococcal disease in adults are quite complicated and not well implemented among many AP areas, and vaccination coverage rates among adults are generally low or perceived as low in the region. Thus, this literature review's purpose was to summarize the disease burden and vaccination against pneumococcal diseases among adults in select AP areas (Australia, Hong Kong, India, Indonesia, South Korea, Malaysia, New Zealand, the Philippines, Singapore, Taiwan, Thailand, and Vietnam). AREAS COVERED: This systematic review included published articles from January 2010 to August 2020 using MEDLINE/Embase. Grey literature websites were searched for national immunization programs and medical society vaccination recommendations from areas of interest. A total of 69 publications were identified. EXPERT OPINION: In the AP region, pneumococcal disease burden and serotype prevalence are variable among adult populations, particularly among older adults. Data was provided primarily from countries with established national immunization programs (NIPs). Further research on the disease burden and emphasis on the benefits of vaccination in AP areas lacking pneumococcal vaccination programs is warranted.

Burden of comorbid anxiety and depression in patients with inflammatory bowel disease: a systematic literature review.

INTRODUCTION: Patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, often have comorbid anxiety and depression that affects their quality of life (QoL) and management of their IBD. AREAS COVERED: A systematic literature review (SLR) was conducted to identify articles and conference abstracts on comorbid anxiety and depression in IBD patients using MEDLINE® and Embase® (January 2003 - June 2018). The impact of these psychological comorbidities on QoL and economic burden was examined. Non-pharmacologic interventions and disease-specific unmet clinical needs associated with these comorbidities were also evaluated. EXPERT OPINION: There is evidence that individual and group-based cognitive behavioral therapy can reduce rates of anxiety and depression in adults and adolescents with IBD. Patients with IBD and anxiety or depression had an increased risk of hospitalization, emergency department visits, readmission, and used outpatient services more often than people without these conditions. Several disease-specific unmet clinical needs for IBD patients were identified. These included lack of reimbursement for mental-health care, inconsistent screening for psychological comorbidities and patients not consulting mental-health professionals when needed. IBD patients may benefit from integrated medical and psychological treatment, and should be considered for behavioral treatment.Plain Language Summary. BACKGROUND: People with IBD may have mental-health conditions, such as anxiety and depression. These conditions can affect people's quality of life and how they manage their IBD. WHAT DID THIS REVIEW LOOK AT?: We found 79 publications on anxiety or depression in people with IBD, published between January 2003 and June 2018. In people with IBD and anxiety or depression, researchers looked at: the impact on health-related quality of life and healthcare utilization, including access to and reimbursement for mental-health services how effective interventions that do not involve the use of medicines were (known as non-pharmacologic therapy). WHAT WERE THE MAIN FINDINGS FROM THIS REVIEW?: People with IBD and anxiety or depression were more likely to be admitted to hospital and visit emergency departments than people without these conditions. Access to mental-health care varied and some people with IBD were not screened for depression.Individual and group-based talking therapy (known as cognitive behavioral therapy) reduced rates of anxiety and depression in some people with IBD. WHAT WERE THE MAIN CONCLUSIONS FROM THIS REVIEW?: We found evidence that people with IBD and anxiety or depression may benefit from certain non-pharmacologic interventions. However, many people with IBD and anxiety or depression did not have access to mental-health services. Healthcare professionals should address gaps in patient care to improve outcomes in people with IBD and anxiety or depression.See Additional file 1 for an infographic plain language summary.

Clinical, humanistic, and economic burden of chronic obstructive pulmonary disease (COPD) in Canada: a systematic review.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic, irreversible disease and a leading cause of worldwide morbidity and mortality. In Canada, COPD is the fourth leading cause of death. This systematic review was undertaken to update healthcare professionals and decision makers regarding the recent clinical, humanistic and economic burden evidence in Canada. METHODS: A systematic literature search was conducted in PubMed, EMBASE, and Cochrane databases to identify original research published January 2000 through December 2012 on the burden of COPD in Canada. Each search was conducted using controlled vocabulary and key words, with "COPD" as the main search concept and limited to Canadian studies, written in English and involving human subjects. Selected studies included randomized controlled trials, observational studies and systematic reviews/meta-analyses that reported healthcare resource utilization, quality of life and/or healthcare costs. RESULTS: Of the 972 articles identified through the literature searches, 70 studies were included in this review. These studies were determined to have an overall good quality based on the quality assessment. COPD patients were found to average 0-4 annual emergency department visits, 0.3-1.5 annual hospital visits, and 0.7-5 annual physician visits. Self-care management was found to lessen the overall risk of emergency department (ED) visits, hospitalization and unscheduled physician visits. Additionally, integrated care decreased the mean number of hospitalizations and telephone support reduced the number of annual physician visits. Overall, 60-68 % of COPD patients were found to be inactive and 60-72 % reported activity restriction. Pain was found to negatively correlate with physical activity while breathing difficulties resulted in an inability to leave home and reduced the ability to handle activities of daily living. Evidence indicated that treating COPD improved patients' overall quality of life. The average total cost per patient ranged between CAN $2444-4391 from a patient perspective to CAN $3910-6693 from a societal perspective. Furthermore, evidence indicated that COPD exacerbations lead to higher costs. CONCLUSIONS: The clinical, humanistic and economic burden of COPD in Canada is substantial. Use of self-care management programs, telephone support, and integrated care may reduce the overall burden to Canadian patients and society.

Comparing common reasons for inpatient and outpatient visits between commercially-insured duloxetine or pregabalin initiators with fibromyalgia.

BACKGROUND: The purpose of this study was to examine the main reasons for inpatient or outpatient visits after initiating duloxetine or pregabalin. METHODS: Commercially insured patients with fibromyalgia and aged 18-64 years who initiated duloxetine or pregabalin in 2006 with 12-month continuous enrollment before and after initiation were identified. Duloxetine and pregabalin cohorts with similar demographics, pre-index clinical and economic characteristics, and pre-index treatment patterns were constructed via propensity scoring stratification. Reasons for inpatient admissions, physician office visits, outpatient hospital visits, emergency room visits, and primary or specialty care visits over the 12 months post-index period were examined and compared. Logistic regression was used to assess the contribution of duloxetine versus pregabalin initiation to the most common reasons for visits, controlling for cross-cohort differences. RESULTS: Per the study design, the duloxetine (n = 3711) and pregabalin (n = 4111) cohorts had similar demographics (mean age 51 years, 83% female) and health care costs over the 12-month pre-index period. Total health care costs during the 12-month post-index period were significantly lower for duloxetine patients than for pregabalin patients ($19,378 versus $27,045, P < 0.05). Eight of the 10 most common reasons for inpatient admissions and outpatient hospital (physician office, emergency room, primary or specialty care) visits were the same for both groups. Controlling for cross-cohort differences, duloxetine patients were less likely to be hospitalized due to an intervertebral disc disorder or major depressive disorder, to have a physician office visit due to nonspecific backache/other back/neck pain (NB/OB/NP) disorder, or to go to specialty care due to a soft tissue, NB/OP/NP, or intervertebral disc disorder. However, duloxetine patients were more likely to have a primary care visit due to a soft tissue disorder, essential hypertension, or other general symptoms. CONCLUSION: Among similar commercially insured patients with fibromyalgia who initiated duloxetine or pregabalin, duloxetine patients had significantly lower health care costs over the 12-month post-index period. The leading reasons for inpatient or outpatient visits were also somewhat different.

Use of select medications prior to duloxetine initiation among commercially-insured patients.

BACKGROUND: The purpose of this study was to assess select medication utilization prior to duloxetine initiation among patients with major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, and musculoskeletal pain associated with osteoarthritis or low back pain. METHODS: Commercially insured duloxetine initiators between January 1, 2007 and March 31, 2010 were identified from a large US administrative claims database. Disease subgroups were constructed based on diagnosis from medical claims during the 12 months prior to duloxetine initiation. Prior use of antidepressants, anticonvulsants, opioids, nonsteroidal anti-inflammatory drugs, and muscle relaxants was assessed during the 12-month preinitiation period. RESULTS: This study identified 56,845 (2007), 44,838 (2008), and 65,840 (January 2009 to March 2010) duloxetine initiators. Among the 2009 initiators, utilization patterns were similar for patients with major depressive disorder and generalized anxiety disorder, with antidepressants being the most used (84% and 80%, respectively), followed by opioids (58% and 55%, respectively). Patients across pain-related conditions also had similar utilization patterns, with opioid use being the highest (76%-82%), followed by antidepressants (65%-72%). Use of other medication classes was common (29%-63%) but less frequent, and over 50% of the patients used any antidepressants, 70% used any antidepressants or anticonvulsants, and 90% used any antidepressants, anticonvulsants, or opioids. Trends in the use of these select medications were similar between 2007 and 2009. CONCLUSION: Patients used several types of medications over the 12 months prior to initiating duloxetine across disease states, with antidepressants and opioids being the most frequently used medications. Trends of select medication use were similar over time.

Combination therapy patterns and predictors of ADHD in commercially insured and Medicaid populations.

OBJECTIVES: Several stimulant and nonstimulant medications are used alone or in combination to treat attention-deficit/hyperactivity disorder (ADHD). Little is known about the current prevalence and predictors of combination therapy. This analysis describes ADHD medication use focusing on combination versus monotherapy. METHODS: Health insurance claims from the Truven Health MarketScan® Commercial Database and Multi-State Medicaid Database were analyzed for patients with an ADHD diagnosis (International Classification of Diseases, Ninth Revision codes 314.0x). Patients included were aged ≥ 6 years as of January 2010, continuously enrolled from July 2009 through December 2010, and had a claim for an ADHD medication in 2010. Medication use was measured in treatment months during 2010. Baseline demographic and clinical predictors of combination therapy (> 1 ADHD medication class in the same month) involving atomoxetine, long-acting stimulants, and α2-adrenergic agonists were explored using logistic regression, with generalized estimating equations to account for within-patient correlation between months. RESULTS: Commercially insured patients with ADHD (N = 211 226) were primarily aged 6 to 17 years (58.4%) and male (61.5%). Attention-deficit/hyperactivity disorder with hyperactivity was present in 15.8% of these patients. Combination therapy was used in 10.3% of 1 125 119 treatment months. Short-acting stimulants and α2-adrenergic agonists had the highest combination use (45.3% and 54.0%, respectively). Patients with ADHD insured through Medicaid (N = 125 104) were primarily aged 6 to 17 years (94.4%) and male (69.5%). Hyperactivity was present in 39.7% of these patients. Combination therapy was used in 24.0% of 721 986 treatment months. Short-acting stimulants, α2-adrenergic agonists, and intermediate-acting stimulants had the highest combination use (70.0%, 63.8%, and 51.8%, respectively). In multivariate models for both data sources, female patients were less likely to use combination therapy. Patients with hyperactivity were more likely to use combination therapy. Tics/Tourette's syndrome was associated with combination therapy for atomoxetine and long-acting stimulants. CONCLUSION: In commercially insured and Medicaid ADHD populations, combination therapy rates differed by medication class, as did the demographic and clinical characteristics statistically significantly associated with combination therapy. This suggests that these medications may be used differently in clinical practice.

Dosing pattern comparison between duloxetine and pregabalin among patients with diabetic peripheral neuropathic pain.

OBJECTIVE: To compare medication dosing patterns of duloxetine and pregabalin among patients with diabetic peripheral neuropathic pain (DPNP). METHODS: Applying a retrospective cohort study design on a large U.S. healthcare claims database, we examined the dosing patterns of duloxetine and pregabalin among commercially insured patients with DPNP aged 18 to 64 who initiated (a 90-day medication gap) duloxetine or pregabalin therapy in 2006. Selected patients had continuous enrollment during the 12-month pre- and post-index periods. The index mediation was used to classified individuals into the duloxetine or pregabalin cohorts. Initial daily dose, average daily dose over the first post-index year, and average daily dose of the first several prescriptions were estimated and compared across the cohorts. RESULTS: The study sample included 828 duloxetine and 1934 pregabalin-treated patients with a mean age of 50 years. Cardiovascular diseases, neuropathic pain other than DPNP, osteoarthritis, and diabetic retinopathy were the most common comorbid conditions. The average initial daily doses were 54.3 and 171.8 mg for duloxetine and pregabalin, respectively. The average daily dose over the first post-index year was 55.2 mg for duloxetine and 173.8 mg for pregabalin. The average daily dose for the first 10 duloxetine prescriptions ranged between 54.3 and 61.9 mg, but increased from 171.8 to 264.3 mg for pregabalin. CONCLUSIONS: The commercially insured patients with DPNP who initiated duloxetine or pregabalin therapy had different dosing patterns. The average daily dose for duloxetine was relatively stable over time, while pregabalin-treated patients had significant dose increase over the 12-month post-index period.

Predictors of pain medication selection among patients diagnosed with fibromyalgia.

OBJECTIVES: Several pharmacologic therapies have been recommended for managing fibromyalgia. However, the factors associated with each treatment initiation have not been well established. This study assessed factors that were associated with the use of duloxetine vs. other pain medications among patients with fibromyalgia. RESEARCH DESIGN AND METHODS: Administrative claims from a large, U.S. commercially insured population were analyzed using a retrospective cohort design. Patients with fibromyalgia who were 18 to 64 years old and initiated duloxetine vs. selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), venlafaxine, gabapentin, pregabalin, tramadol, or nontramadol opioids between January 1, 2007 and December 12, 2008 were selected. Treatment initiation was defined as no access to the same medication over the previous 90 days, with the most recent initiation date as the index date. All patients selected had at least one fibromyalgia diagnosis (ICD-9-CM: 729.1) in the 12 months prior to initiation of each study medication. Multiple logistic regression models were estimated to assess the predictors of initiating duloxetine vs. each of the other medications. RESULTS: The study included 117,305 patients with fibromyalgia (48 years of age on average; 76% women) who initiated duloxetine (n = 5,827), SSRIs (n = 8,620), TCAs (n = 5,424), venlafaxine (n = 2,038), gabapentin (n = 5,733), pregabalin (n = 11,152), tramadol (n = 7,312), or nontramadol opioids (n = 71,199). Common fibromyalgia-related comorbidities were low back pain (31% to 49%), osteoarthritis (14% to 21%), and sleep disturbance (10% to 15%). Controlling for demographic and clinical characteristics, patients who received pregabalin in the prior 12-month period were more likely to initiate duloxetine. Patients from other treatment cohorts, except for those in the pregabalin and nontramadol opioid cohorts, were more likely to re-initiate the same prior medication than to begin treatment with duloxetine. Other predictors of duloxetine initiation included history of rheumatoid and sleep disturbance. CONCLUSIONS: The presence of select comorbidities and prior use of certain medications were associated with the duloxetine initiation among working-age, commercially insured patients with fibromyalgia.