Single- versus multiple-tablet HIV regimens: adherence and hospitalization risks.

OBJECTIVES: To evaluate the impact of antiretroviral therapy as a single-tablet regimen (STR) and multiple-tablet regimen (MTR) on outcomes in human immunodeficiency virus (HIV)/AIDS patients using electronic health records from the Veterans Healthcare Administration (VHA). STUDY DESIGN: Retrospective cohort. METHODS: This study evaluated VHA patients to whom HIV medications were dispensed as STRs or MTRs during the study period (January 1, 2006, to July 30, 2012). Patients were followed from the index date (ie, start of regimen) until treatment discontinuation, end of study period, last date of healthcare-related activity, or death. Differences in outcomes of hospitalization, adherence defined as a medication possession ratio of ≥ 95%, and undetectable viral load were evaluated using a Cox-proportional hazard and logistic model controlling for covariates measured during a 6-month baseline period. RESULTS: A total of 15,602 patients (6191 STR and 9411 MTR) met all study criteria. The study sample was, on average, aged 52 years with similar CD4 counts (mean ± SD: 432.2 ± 282.8 vs 419.3 ± 280.9; P = .287), but a significantly lower proportion of STR versus MTR patients had an undetectable viral load at baseline (42% vs 46%; P < .001). After controlling for baseline covariates, the STR cohort had twice the odds of being adherent (odds ratio [OR], 1.98; P < .001), 31% had a significantly lower hazard of having a hospitalization (hazard ratio, 0.69; P < .001), and 21% had higher odds of having an undetectable viral load during follow-up (OR, 1.21; P < .001). CONCLUSIONS: STR is associated with higher adherence rates, decreased hospitalizations, and more patients with an undetectable viral load in VHA patients with HIV/AIDS.

Economic considerations for mid-urethral sling procedures among patients with stress urinary incontinence.

OVERVIEW: Stress urinary incontinence (SUI) is associated with a hefty economic burden. Retropubic and transobturator vaginal slings have become common surgical options for women with SUI. This study examines the costs of transobturator slings for SUI surgeries. METHODS: A model was created to estimate the budget impact to hospitals of transobturator sling surgery in women with SUI. Current practice using transobturator slings including the MonarcTM Subfascial Hammock, Obtryx® Transobturator Mid-Urethral Sling System, Aris® Transobturator Sling System, Align® TO Trans-Obturator Urethral Support System, GYNECARE TVTTM Obturator System Tension-free Support for Incontinence and GYNECARE TVT ABBREVOTM Continence System were modeled. Four surgical complications were considered: re-operation due to failure, revision or removal of sling, urologic complications including urinary obstruction and urinary tract infection, and pelvic complications. This model calculates the average 1-year cost per patient with the use of each sling product and estimates the total budget for sling urinary incontinence surgery associated with each product based on these calculations. RESULTS: Average incremental cost over 1 year ranged from $2,601 (GYNECARE TVTTM Obturator) to $3,132 (Desara®) per patient. In a hypothetical population of 100 patients, a 10% shift from the most to the least expensive option was associated with a 2% decrease in hospital expenditures. With the current market share for transobturator sling products, the expected expenditure is around $285,533 for a surgical population of 100 patients. Sling costs account for approximately $105,526 (37%) of this cost, with complications comprising the remaining majority. CONCLUSION: This study represents the first comparative assessment of the costs of different sling options for stress urinary incontinence surgeries. GYNECARE TVT ABBREVOTM and GYNECARE TVTTM Obturator products represent a sound clinical and economic choice for hospitals. Moreover, the reduction in expenditures is obtained at the benefit of patients, who experience fewer complications and avoid complication-related procedures.

Long-term patterns of use and treatment failure with anticholinergic agents for overactive bladder.

BACKGROUND: Overactive bladder (OAB) involves a complex set of symptoms with a lifetime prevalence of any symptom in ~30% of women and 20% of men. Anticholinergic agents are associated with poor medication persistence in OAB treatment. OBJECTIVE: This study evaluated the long-term patterns of use and treatment failure in patients prescribed anticholinergic agents for OAB. METHODS: This was a nonexperimental, retrospective cohort study. Medical, pharmacy, and eligibility data from the IMS LifeLink Health Plans Claims Database were used. Men and women aged ≥18 years were eligible for inclusion with an International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis of OAB in any field during the patient study period from January 2005 to June 2010. First documentation of a prescription filled between July 2005 and June 2008 for an anticholinergic agent was defined as the index prescription. Other inclusion criteria were: ≥1 pharmacy claim for an anticholinergic drug between July 2005 and June 2008; continuous enrollment 6 months before the index date, during which no anticholinergic drugs were filled; and 24 months of follow-up from the index prescription. Study outcomes were treatment failure, discontinuation, switch, reinitiation, and adherence. Treatment failure was defined as having a treatment discontinuation (ie, treatment gap of ≥45 days) or switching anticholinergic therapy. RESULTS: The analytic cohort comprised 103,250 patients with a mean age of 58.7 years. A majority were female (73%) and privately insured (75%). The vast majority of patients (91.7%) failed to meet their treatment goals with their index anticholinergic agent over the 24-month follow-up period. Of these, 5.8% switched, 51.3% permanently discontinued all anticholinergic agents, and 34.6% reinitiated treatment sometime after 45 days. The mean (SD) time to treatment failure was 159 (216.0) days, with a mean of 1.3 (0.5) unique anticholinergic agents per patient. Forty-eight percent of patients demonstrated appropriate adherence as determined by a medication possession ratio ≥80%. CONCLUSIONS: This study provides real-world data on treatment patterns over 2 years in a large cohort of patients diagnosed with OAB. Despite the potential for better adherence with some anticholinergic agents, these analyses suggest that such benefits have not yet been realized, and many patients end up without effective pharmacotherapy. Thus, there is a need for new therapies and strategies to increase persistence and adherence to improve outcomes in OAB.

Surveillance and treatment of non-muscle-invasive bladder cancer in the USA.

Seventy percent of newly diagnosed bladder cancers are classified as non-muscle-invasive bladder cancer (NMIBC) and are often associated with high rates of recurrence that require lifelong surveillance. Currently available treatment options for NMIBC are associated with toxicities that limit their use, and actual practice patterns vary depending upon physician and patient characteristics. In addition, bladder cancer has a high economic and humanistic burden in the United States (US) population and has been cited as one of the most costly cancers to treat. An unmet need exists for new treatment options associated with fewer complications, better patient compliance, and decreased healthcare costs. Increased prevention of recurrence through greater adherence to evidence-based guidelines and the development of novel therapies could therefore result in substantial savings to the healthcare system.

Potential drug-drug interactions with antiepileptic drugs in Medicaid recipients.

PURPOSE: The frequency of potential drug-drug interactions (DDIs) between antiepileptic drugs (AEDs) and other (non-AED) medications in Medicaid patients taking newer AED monotherapy, older AED monotherapy, and combinations of AED treatment was studied. METHODS: A retrospective, observational study was conducted using administrative claims obtained from South Carolina Medicaid. Patients were included in the analysis if they (1) had at least one prescription for an AED between January 1, 2004, and December 31, 2004, (2) were taking a specific AED for at least 60 days, (3) had at least one epilepsy diagnosis during the 6 months before or during the enrollment period, and (4) were enrolled in Medicaid for at least 11 of the 12 months of the follow-up period. Possible DDI exposure was defined as 10 days of overlap between an AED and a non-AED known to have the potential to cause a clinically relevant interaction. RESULTS: A total of 4955 patients met the inclusion criteria. Approximately 45% of patients receiving monotherapy with an older AED had a potential DDI, compared with 3.9% receiving a newer AED. An average of 0.08 potential DDI per year of exposure occurred in the newer AED monotherapy cohort compared with 1.18 in the older AED monotherapy cohort. The most common potential interaction category was a decreased concentration of the non-AED. CONCLUSION: Older AEDs were associated with a greater likelihood of a potential DDI than were newer AEDs. Further research is needed to elucidate the relationship between the occurrence of potential DDIs and actual clinically relevant consequences.

Current management of glaucoma and the need for complete therapy.

Glaucoma is a long-term ocular neuropathy defined by optic disc or retinal nerve fiber structural abnormalities and visual field abnormality. Primary open-angle glaucoma is the most common type of glaucoma. Currently available treatments, initiated in a stepwise process, focus on intraocular pressure (IOP) reduction, and initially include topical drug therapy (single then multidrug combinations), followed by laser then surgical treatment. Topical prostaglandin analogues or beta-adrenergic receptor blockers are first used, followed by alpha-agonists or topical carbonic anhydrase inhibitors, and infrequently, cholinergic agonists and oral therapy. Limitations to existing topical IOP-reducing medications include continued disease progression in glaucoma patients with normal IOP, treatment failure, and low rates of compliance and persistence. Therapeutic agents under investigation include neuroprotectants, which target the disease process manifested by death of retinal ganglion cells, axonal loss, and irreversible loss of vision. Neuroprotectants may be used alone or in combination with IOPreducing therapy (a treatment strategy called complete therapy). Memantine, an N-methyl-D-aspartate receptor blocker currently approved for dementia, is the neuroprotectant farthest along in the process seeking regulatory approval for glaucoma treatment and has a favorable safety profile because of its selective mechanism of action. Several other neuroprotectants are in early stage investigation. Complete therapy provides hope for improved outcomes by reducing the significant morbidity and economic consequences that occur as a result of neurodegeneration and disease progression.

Disease progression and the need for neuroprotection in glaucoma management.

Glaucoma, the second leading cause of worldwide blindness, is a progressive optic neuropathy characterized by a loss of retinal ganglion cells and their axons beyond typical age-related baseline loss. Diagnosis is defined by optic disc and visual field changes, and the primary goal of glaucoma treatment is to preserve vision. Proven existing therapies (ie, pharmacotherapy, laser, and surgical) focus on reduction of intraocular pressure (IOP), although elevated IOP is no longer a diagnostic feature of glaucoma. New neuroprotectant drugs are being investigated, with the goal of reducing retinal ganglion cell loss, either prophylactically or after the insult has occurred. Various treatment strategies are being evaluated, and include a neuroprotectant only, or a complete therapy approach comprised of both a neuroprotectant supplemented by an IOP-lowering therapy. Dually targeted complete therapy may directly preserve the optic nerve, decrease the risk factors that cause glaucoma damage, and reduce glaucoma-related morbidities. Neuroprotectant therapy outcomes should include functional and structural effects of disease progression and neuroprotectant therapies, as well as patient functioning and economic impact.

Managed care and the impact of glaucoma.

Changes in the healthcare system, population demographics, and treatment alternatives have contributed to an emerging awareness of glaucoma among managed care organizations. Early diagnosis and treatment are essential to thwarting the personal and economic consequences of end-stage glaucoma. Despite recognition of the need for early intervention and therapy, the literature suggests a great need still exists for improvements in lowering intraocular pressure, managing appropriate follow-up, and improving adherence to current glaucoma medication regimens. As the elderly population continues to increase, these issues will intensify and present further problems for the healthcare system. The purpose of this introductory manuscript is to highlight the literature on the clinical and economic impact of glaucoma and its importance to the managed care community. The remainder of the supplement will focus on the current management of glaucoma and the potential role of neuroprotection in this patient population.

Current landscape of insomnia in managed care.

Insomnia affects a large percentage of the population, particularly the elderly. Literature reports varying estimates of prevalence, a variation that relates to the lack of definition and consistency in diagnostic criteria. Primary insomnia (not caused by known physical/mental conditions) responds to pharmacologic therapy, while secondary insomnia(resulting from other illnesses, medications, or sleep disorders) responds to pharmacologic and psychologic treatments (cognitive therapy, relaxation techniques, stimulus control). Use of certain agents in the elderly and patients with abuse/addiction potential is a concern. Medicare Part D does not cover benzodiazepines (classified as controlled substances). Nonprescription agents are affordable but have sedation and anticholinergic side effects. Medication use should be considered a possible contributing factor. Insomnia patients experience significantly more limited activity and higher total health services than those without insomnia. Annual costs are between $92.5 billion and $107.5 billion. A standard definition and better pathways to recognize and treat insomnia are needed.

The state of insomnia and emerging trends.

Recent research into the pathophysiology of insomnia has brought a shift in the approach to treatment. Insomnia rarely occurs in isolation and is typically comorbid with other conditions. Rather than simply treating the primary disorder, whereby symptoms of insomnia may go unaddressed, now there is a push to acknowledge the existence of chronic insomnia as a disorder that itself merits treatment. This recognition is due to the identification of pathophysiologic changes and associated morbidity, which can be substantial. Insomnia patients have increased risk for psychiatric disorders, especially depression, anxiety, decreased quality of life, increased healthcare utilization and costs, drug/alcohol abuse, decreased occupational performance, and increased falls/accidents. Current management patterns explore non-nightly or discontinuous hypnotic treatment - non-nightly flexible, non-nightly semiflexible, non-nightly fixed, and flexible timing - which deviates from past trends of continuous dosing with hypnotics. These trends reflect a change from considering insomnia a symptom to treating insomnia as a disorder.

Circadian rhythmicity and the pharmacologic management of insomnia.

The circadian clock modulates timing of sleep and wakefulness. In certain situations, the circadian potentiation of wakefulness may interfere with desired sleep-scheduling, particularly in the elderly and shift workers. Known abnormalities of circadian regulation are defined by their impact on sleep-wake state expression. In delayed sleep phase syndrome, patients have trouble going to sleep and arising at reasonable hours and are alert in the evening and sleepy in the morning. Patients with advanced sleep phase syndrome are sleepy in the evening and awaken very early and alert in the morning. In shift-work sleep disorder, individuals attempt to wake and sleep out of phase with the circadian clock. As with jet lag, the clock is functioning normally, but the requirements on the clock are abnormal. Typical insomnia can also be associated with circadian rhythm alterations. Practice guidelines and clinical studies data are needed to lead appropriate therapy selection and effective management.

Chronic insomnia treatment and Medicare Part D: implications for managed care organizations.

The elderly population is of particular concern with regard to insomnia and managed care. Early intervention and management of insomnia as a chronic disease are recommended. Increased awareness of the negative clinical and economic consequences associated with not treating insomnia may serve to raise the perceived importance of having effective formulary options for this disease area. Because the elderly population is now covered by Medicare Part D, health plans previously without a Medicare drug benefit must now select and reimburse for sedative-hypnotics for the elderly. A review of the major Medicare Part D plans' formularies reveals they offer a limited number of sedative-hypnotic alternatives, but not all are available. Due to variable response, variation in comorbidities, drug and disease interactions, and individual patient needs, managed care organizations should cover a reasonable array of drugs. This is essential to optimally manage patients with chronic insomnia to reduce the long-term clinical morbidity and economic consequences.

Topiramate prescribing patterns among medicaid patients: diagnosis, comorbidities, and dosing.

BACKGROUND: Routine clinical practice data are useful for payers and formulary decision makers to make sound decisions regarding coverage policy. Based on a literature search, there has been scant research into topiramate prescribing patterns among Medicaid patients. OBJECTIVE: The aim of this study was to describe diagnoses, demographic characteristics, additional co-existing diagnoses, and dosing among Medicaid patients prescribed topiramate. METHODS: This descriptive, retrospective database analysis used data from South Carolina (SC) and Texas (TX) ambulatory Medicaid claims dated October 1, 2003, to December 31, 2004. Patients whose data were eligible for inclusion in the study were enrolled in Medicaid during the study period, had >or=2 topiramate prescriptions, were aged <65 years, and had evidence of a topiramate treatment-related diagnosis (possible diagnoses were identified through literature search and drug compendiums). Four cohorts were defined: (1) epilepsy only; (2) migraine only; (3) epilepsy and migraine; and (4) nonepilepsy/nonmigraine. Demographic characteristics, diagnoses, comorbidities, and daily dose of topiramate were summarized using descriptive statistics. The initial study analysis (period 1) was a 180-day window comprising the 90 days before and after the first available topiramate prescription claim was filed. A second, 360-day analysis (period 2) was completed comprising the 180 days before and after the index topiramate prescription date. RESULTS: In the 180-day analysis, 2216 SC and 4766 TX Medicaid patients met the selection criteria. Cohort classification percentages were 32.3% and 39.6% (epilepsy only), 29.7% and 16.4% (migraine only), 10.7% and 9.2% (epilepsy and migraine), and 27.3% and 34.9% (nonepilepsy/nonmigraine) for SC and TX, respectively. Mean (SD) ages were 29.9 (15.9) (SC) and 27.1 (16.1) (TX) years. In the nonepilepsy/nonmigraine cohort, the most common diagnoses were bipolar disorder and depression. The median daily doses in the epilepsy-only cohort were 175 mg/d in the SC group and 200 mg/d in the TX group. In the migraine-only cohort, the median daily dose was 100 mg/d in SC and TX. Results for the 360-day analysis were similar. CONCLUSIONS: In this descriptive study using data from 2 Medicaid populations, the majority of patients using topiramate had a diagnosis of epilepsy and/or migraine. Median dosages ranged from 175 to 200 mg/d in patients with epilepsy and 100 mg/d in those with migraine. Depression was a common comorbidity in the migraine cohort and the nonepilepsy/nonmigraine cohort.

Relationship of blood pressure control to adherence with antihypertensive monotherapy in 13 managed care organizations.

OBJECTIVE: This study was conducted to evaluate the relationship between medication compliance and blood pressure (BP) control among members of 13 managed care organizations with essential hypertension (HTN) who received antihypertensive monotherapy for at least 3 pharmacy claims prior to the blood pressure measurement. METHODS: This was a retrospective review of medical and pharmacy claims over a 4-year period (1999-2002) from 13 U.S. health plans. Data were collected by trained health professionals from randomly selected patient medical records per Health Plan Employer Data and Information Set (HEDIS) technical specifications. Patients were selected if they (1) had received monotherapy or fixed-dose combination therapy (administered in one tablet or capsule) during the time BP was measured (thus those with no BP drug therapy were excluded); (2) had received 3 or more antihypertensive pharmacy claims for the antihypertensive drug therapy prior to BP measurement; and (3) had one or more antihypertensive pharmacy claims after BP was measured. Control of BP was defined according to guidelines of the Sixth Report of the Joint National Committee (JNC 6) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (<140/90 mm Hg, or <130/85 mm Hg for patients with diabetes). Medication adherence was measured using the medication possession ratio (MPR), and MPR was used to classify patients into 3 adherence levels: high (80%-100%), medium (50%-79%), and low (<50%). The relationship between medication adherence and BP control was assessed using a logistic regression model. RESULTS: There were 1,017,181 patients with a diagnosis of HTN in medical claims data from which 10,734 (10.6%) were randomly selected for chart review. There were 1,032 patients (9.6%) in the sample who had a diagnosis of HTN but who were excluded because they had no HTN drug therapy. Of the total 9,894 patients (92.2%) who were excluded from the sample, 3,029 patients (28.2%) met all other inclusion criteria but were receiving more than one HTN drug. Of the 840 patients on HTN monotherapy, the mean age was 59 12.2 years; 422 (50%) were women, 16% had diabetes, and 43% had dyslipidemia. The monotherapy HTN drug was an angiotensin-converting enzyme inhibitor (27% of patients), calcium channel blocker (22%), beta-blocker (20%), or diuretic (11%). Of the 840 patients, 629 (74.8%) were determined to have high medication adherence, 165 (19.6%) had medium adherence, and 46 (5.5%) had low adherence. Approximately 270 (43%) of high adherence patients achieved BP control compared with 56 (34%) and 15 (33%) patients with medium and low adherence, respectively. High-adherence patients were 45% more likely to achieve BP control than those with medium or low compliance after controlling for age, gender, and comorbidities (odds ratio=1.45; P =0.026). CONCLUSION: These results demonstrate that 75% of these health plan members with a diagnosis of essential HTN who were selected for receipt of at least 4 pharmacy claims for HTN monotherapy exhibited high medication adherence. However, only 43% of high-adherence patients attained their target (JNC 6) blood pressure goal compared with 33% to 34% of patients with medium or low adherence to antihypertensive monotherapy.

Development of a predictive index for picornavirus infections.

To create a clinical prediction index that aids in the diagnosis of picornavirus respiratory infections, we analyzed patients from 5 clinical trials designed to evaluate the efficacy of an antiviral treatment for respiratory infections. Logistic regression was used to determine which baseline symptoms and patient characteristics best predicted picornavirus infection. Parameter estimates were then used to create a predictive index for estimating the probability of picornavirus infection on the basis of cold symptoms. The presence at baseline of rhinorrhea (odds ratio [OR], 2.73), nasal congestion (OR, 1.63), and sore throat (OR, 1.37) increased the likelihood of picornavirus infection; the presence of myalgia (OR, 0.71) and fever (OR, 0.59) decreased the likelihood. The positive and negative predictive values of the model were 61.5% and 64.4%, respectively. The model was simplified for clinical use by creating a whole-number index: the lowest possible score (-3) indicates a 15% chance of picornavirus infection and the highest (7) indicates a 69% chance of picornavirus infection.

Determinants of uncontrolled hypertension in an African-American population.

OBJECTIVES: The purpose of this study was to assess blood pressure control and the determinants of uncontrolled blood pressure among African-American hypertensive patients. DESIGN: Baseline clinical data were collected as part of a nationwide hypertension quality improvement initiative. An analysis of determinants of uncontrolled blood pressure was conducted using logistic regression for the following variables: angina, congestive heart failure, coronary artery disease, diabetes, family history of cardiovascular disease or stroke, hyperlipidemia, left ventricular hypertrophy, and tobacco use. SETTING: 10 managed care/advanced physician organizations. PATIENTS: Pharmacy and medical claims covering 1,965,000 lives were reviewed and 292,996 members with a hypertension-related claim were identified between June 1, 1998 and July 1, 2001. A random sample (N = 5,935) was selected for chart review. The present analysis was conducted on the subset of African-American patients (N = 440) included in this sample. RESULTS: Approximately 66% of the African-American patients were female, the mean age was 60.4 years, 47.8% had dyslipidemia, and 31.4% had diabetes. Approximately 64% had uncontrolled hypertension. Patients with diabetes were 3 times more likely to have uncontrolled blood pressure as were patients without diabetes (OR = 2.92; P < .0001). CONCLUSIONS: Blood pressure control in the African-American population is lower than the Healthy People 2010 goal of 50%. African Americans with hypertension and diabetes are at an increased risk for uncontrolled blood pressure. Treating this high-risk population more aggressively may reduce long-term complications and decrease mortality.

Productivity losses related to the common cold.

Health-related productivity assessments typically focus on chronic conditions; however, acute conditions, particularly colds, have the potential to cause substantial health-related productivity losses because of their high prevalence in working-age groups. This article presents the findings of a study conducted to estimate productivity loss due to cold by using a telephone-administered survey that measured three sources of loss: absenteeism, on-the-job productivity, and caregiver absenteeism. Each cold experienced by a working adult caused an average of 8.7 lost work hours (2.8 absenteeism hours; 5.9 hours of on-the-job loss), and 1.2 work hours were lost because of attending to children under the age of 13 who were suffering from colds. We conclude that the economic cost of lost productivity due to the common cold approaches $25 billion, of which $16.6 billion is attributed to on-the-job productivity loss, $8 billion is attributed to absenteeism, and $230 million is attributed to caregiver absenteeism.