Cost and Utilization of Behavioral Health Medications Associated with Rescission of an Exemption for Prior Authorization for Severe and Persistent Mental Illness in the Vermont Medicaid Program

BACKGROUND: In recent years, many state Medicaid programs have implemented preferred drug lists (PDL) to control pharmaceutical costs by generating supplemental rebate revenues and directing providers to the most cost-effective treatments. Two states, Michigan and Vermont, sought approval from the Centers for Medicare and Medicaid Services for supplemental rebates for their Medicaid fee-for-service programs in 2002. Behavioral health medications were largely excluded from PDLs and other managed care initiatives implemented by state Medicaid programs because of significant opposition to any impact on this vulnerable population. In November 2001, the Vermont Medicaid program implemented the Vermont Health Access Pharmacy Benefit Management Program, a PDL designed to promote cost-effective use of medications. Despite the potential cost savings resulting from implementation of a PDL, behavioral health providers and advocates in the state of Vermont opposed the implementation of the managed care initiative for beneficiaries with severe mental illness, and after January of 2002, Vermont\u27s program was changed to exempt beneficiaries meeting the severe and persistent mental illness (SPMI) criteria from prior authorization (PA) for behavioral health medications not on the Medicaid PDL. The SPMI exemption was phased out by June 30, 2006. OBJECTIVES: To determine the effects of the rescission of the PA exemption on utilization and costs of 3 classes of behavioral health medications (antidepressants, antipsychotics, and anxiolytics/sedatives). Secondary analyses were conducted to assess the association between rescission of the PA exemption and 2 quality measures that might be associated with pharmacy management policy: (a) behavioral health hospitalizations and (b) high-dose prescribing of antipsychotics, defined as dosing that exceeded the manufacturer-recommended maximum dose by 25%. METHODS: This was a retrospective analysis of pharmacy claims for beneficiaries of the Office of Vermont Health Access Medicaid Program for dates of service from July 1, 2005, through December 31, 2007. The 12-month PA exemption period for 3 categories of drugs (antidepressants, antipsychotics, and anxiolytics/sedatives) was July 1, 2005, through June 30, 2006; and the post-PA exemption period was the 12 months from January 1, 2007, through December 31, 2007, following rescission of the SPMI exemption. Costs in this analysis were defined as the amount paid by Medicaid, excluding federal drug rebates paid by drug manufacturers and supplemental rebates associated with the PDL program. Costs were adjusted for inflation using the Consumer Price Index for medical costs. Frequencies were used to identify trends between medication classes and time periods. Medical claims from the 2 time periods were used to assess inpatient hospitalization trends. Descriptive statistics, Pearson chi-square tests (for categorical data), and t-tests (for continuous data) were used to assess the 2 study cohorts. RESULTS: 17.8% (n=22,130) of 124,169 eligible beneficiaries in the PA exemption period had 1 or more pharmacy claims in the 3 classes of medications exempt from PA versus 19.2% (n=23,717) of 123,499 eligible beneficiaries in the post-PA exemption period. Utilization of behavioral medications per member per month (PMPM) increased by 14.3% from 0.14 claims PMPM in the PA exemption period to 0.16 claims PMPM in the post-PA exemption period, similar to the 14.1% increase in the utilization of nonbehavioral medications (from 0.64 to 0.73 claims PMPM). Utilization changed little between the PA exemption period and the post-PA exemption period for the 3 individual classes of behavioral health drugs, 0.08 claims PMPM versus 0.09 claims PMPM for antidepressants and 0.03 for both study periods for both antipsychotics and anxiolytics/sedative hypnotics. PMPM costs for the 3 drug classes exempt from PA increased by 2.1% from $12.76 to$13.03, compared with a 12.2% increase from $42.58 PMPM to$47.79 PMPM for nonbehavioral health medications. The small 2.1% increase in PMPM costs for the 3 formerly PA-exempt drug classes was attributable in part to a 12.9% reduction in average cost per pharmacy claim, from $94.05 to$81.92, including a 24.8% reduction in the average cost per antidepressant claim, from $65.59 to$49.33. For the subgroup of beneficiaries taking atypical antipsychotic medications, the percentage with high-dose prescriptions decreased from 3.1% to 2.2%. Mental health inpatient hospitalizations also decreased from 0.6% of beneficiaries in the PA exemption period to 0.4% in the post-PA exemption period. CONCLUSIONS: In a Medicaid population excluding Medicare dual-eligible beneficiaries, the rescission of a PA exemption for 3 major classes of behavioral health medications in a PDL was not associated with decreased utilization of formerly PA-exempt behavioral health medications. The increase in PMPM spending for the formerly PA-exempt behavioral health medications was small compared with the increase in PMPM cost for nonbehavioral health medications, and there were fewer beneficiaries with hospitalization for mental health reasons in the period after rescission of the PA exemption

OnabotulinumtoxinA muscle injection patterns in adult spasticity: a systematic literature review

BACKGROUND: OnabotulinumtoxinA has demonstrated significant benefit in adult focal spasticity. This study reviews the injection patterns (i.e., muscle distribution, dosing) of onabotulinumtoxinA for treatment of adult spasticity, as reported in published studies. METHODS: A systematic review of clinical trials and observational studies published between 1990 and 2011 reporting data on muscles injected with onabotulinumtoxinA in adult patients treated for any cause of spasticity. RESULTS: 28 randomized, 5 nonrandomized, and 37 single-arm studies evaluating 2,163 adult patients were included. The most frequently injected upper-limb muscles were flexor carpi radialis (64.0% of patients), flexor carpi ulnaris (59.1%), flexor digitorum superficialis (57.2%), flexor digitorum profundus (52.5%), and biceps brachii (38.8%). The most frequently injected lower-limb muscles were the gastrocnemius (66.1% of patients), soleus (54.7%), and tibialis posterior (50.5%). The overall dose range reported was 5–200 U for upper-limb muscles and 10–400 U for lower-limb muscles. CONCLUSIONS: The reviewed evidence indicates that the muscles most frequently injected with onabotulinumtoxinA in adults with spasticity were the wrist, elbow, and finger flexors and the ankle plantar flexors. OnabotulinumtoxinA was injected over a broad range of doses per muscle among the studies included in this review, but individual practitioners should be mindful of local regulatory approvals and regulations

Extended dual antiplatelet therapy with ticagrelor 60 mg in patients with prior myocardial infarction: The design of ALETHEIA , a multi‐country observational study

Introduction: Clinical guidelines recommend extended treatment with dual antiplatelet therapy (DAPT) with ticagrelor 60 mg (twice daily) beyond 12 months in high-risk patients with a history of myocardial infarction (MI) who have previously tolerated DAPT and are not at heightened bleeding risk. However, evidence on patterns of use and associated clinical outcomes in routine clinical practice is limited. Methods: ALETHEIA is an observational, multi-country study, designed to describe characteristics, treatment persistence, and bleeding and cardiovascular (CV) outcomes in post-MI patients who initiate ticagrelor 60 mg in routine clinical practice (NCT04568083). The study will include electronic health data in the United States (US; Medicare, commercial claims) and Europe (Sweden, Italy, United Kingdom, Germany). Characteristics will be described among patients with and without ticagrelor 60 mg ≥1 year post-MI. Assuming an a priori threshold of 5000 person-years on-treatment is met, to ensure sufficient precision, clinical outcomes (bleeding and CV events) among patients treated with ticagrelor 60 mg will be assessed. Risk factors for clinical outcomes and treatment discontinuation will be assessed in patients with ticagrelor 60 mg and meta-analysis used to combine estimates across databases. Cohort selection will initiate from the ticagrelor 60 mg US and European approval dates and end February 2020. An estimated total of 7250 patients prescribed ticagrelor 60 mg are expected to be included. Discussion: An increased understanding of patterns of ticagrelor 60 mg use and associated clinical outcomes among high-risk patients with a prior MI is needed. The a priori specified stepwise approach adapted in this observational study is expected to generate useful evidence for clinical decision-making and treatment optimization

Mycobacterium marinum antagonistically induces an autophagic response while repressing the autophagic flux in a TORC1- and ESX-1-dependent manner.

Autophagy is a eukaryotic catabolic process also participating in cell-autonomous defence. Infected host cells generate double-membrane autophagosomes that mature in autolysosomes to engulf, kill and digest cytoplasmic pathogens. However, several bacteria subvert autophagy and benefit from its machinery and functions. Monitoring infection stages by genetics, pharmacology and microscopy, we demonstrate that the ESX-1 secretion system of Mycobacterium marinum, a close relative to M. tuberculosis, upregulates the transcription of autophagy genes, and stimulates autophagosome formation and recruitment to the mycobacteria-containing vacuole (MCV) in the host model organism Dictyostelium. Antagonistically, ESX-1 is also essential to block the autophagic flux and deplete the MCV of proteolytic activity. Activators of the TORC1 complex localize to the MCV in an ESX-1-dependent manner, suggesting an important role in the manipulation of autophagy by mycobacteria. Our findings suggest that the infection by M. marinum activates an autophagic response that is simultaneously repressed and exploited by the bacterium to support its survival inside the MCV

An innovative approach to pharmacy management in a state correctional system

Numerous models are employed for medication distribution and pharmacy services management in correctional facilities. Since 2003, the University of Rhode Island College of Pharmacy and the Rhode Island Department of Corrections (RIDOC) have collaborated on a pharmacy management program designed to better integrate medical care, improve medication utilization, and reduce pharmaceuticals costs. The program introduced staff education, waste-reduction strategies, treatment protocols, and a responsive formulary system. RIDOC pharmaceutical expenditures grew at a rate of approximately 1.5% Per Inmate Per Year from 2003 to 2009, considerably below the annual pharmaceutical inflation rate. Analyses of projected and actual drug spending indicate that RIDOC benefited from savings of almost $5 million during this period. This innovative approach to pharmacy management addressed many pharmaceutical care issues that had challenged RIDOC while providing educational opportunities for doctor of pharmacy students in this practice setting. © NCCHC 2012

The incidence and costs of hypoglycemia in type 2 diabetes

Objectives: To estimate the rate and costs of hypoglycemia in patients with type 2 diabetes. Study Design: We used a retrospective cohort design to assess the rate and costs of hypoglycemia among working-age patients with type 2 diabetes in the 2004 to 2008 MarketScan database. Methods: We followed patients from cohort entry to the first instance of hypoglycemia requiring medical intervention (inpatient, emergency department [ED], or outpatient) and calculated incidence rates (IRs), stratifying these estimates by age (18-34, 35-49, 50-64, and 65+ years) and gender. We calculated inflation-adjusted total and mean direct costs of medical visits for hypoglycemia, other diabetes-related visits, and all other medical visits. Results: The cohort was composed of 536,581 members with approximately 1.21 million personyears (p-yrs) of follow-up. The IR of hypoglycemic events leading to an inpatient admission, ED, or outpatient visit was 153.8/10,000 p-yrs. The IRs of hypoglycemic events were highest in adults aged 18 to 34 years (218.8/10,000 p-yrs). Regardless of age group, rates of hypoglycemia were greater in women than in men (P \u3c.001). Total hypoglycemia costs were $52,223,675 over the study period and accounted for 1.0$17,564 for an inpatient admission, $1387 for an ED visit, and$394 for an outpatient visit. Conclusions: The overall incidence of visits for hypoglycemia was considerable in this large database, and was associated with high per-episode costs. Continued vigilance and the development of strategies to decrease potentially avoidable hypoglycemic episodes requiring medical intervention are needed

Gaucher disease epidemiology and natural history: a comprehensive review of the literature

<p><b>Objectives:</b> The objectives of this research were: (1) to heighten awareness of Gaucher disease (GD), a rare lysosomal storage disorder with highly heterogeneous patterns of organ involvement and disease severity, to clinicians most likely to encounter these patients, and; (2) to summarize the published evidence on GD epidemiology which is essential to accurately depict the total societal burden of this rare worldwide disorder.</p> <p><b>Methods:</b> A comprehensive literature review was undertaken to summarize the published evidence on the epidemiology of GD. MEDLINE, EMBASE, CENTRAL, and ‘grey’ literature sources published in English between January 1990 and March 2015 were searched to identify relevant publications.</p> <p><b>Results:</b> In total, 188 full-text articles were reviewed and findings from 49 studies are summarized herein. The standardized birth incidence of GD in the general population varied from 0.39 to 5.80 per 100 000, and prevalence ranged from 0.70 to 1.75 per 100 000, respectively. Time from onset of GD symptoms to clinical diagnosis was highly variable, with median delays of up to 7 years reported.</p> <p><b>Discussion:</b> The incidence and prevalence of GD is substantially higher among the Ashkenazi Jewish population than the general population. Limited epidemiologic information was available from Latin America, Africa, Asia, and developed nations such as the United States, Germany, and the United Kingdom.</p> <p><b>Conclusions:</b> Signs and symptoms of GD frequently mimic more common hematologic conditions resulting in missed or delayed diagnosis. Early diagnosis and prompt initiation of treatment when indicated is crucial to prevent or minimize life-altering or life-threatening liver and skeletal complications.</p

Adherence and persistence with prasugrel following acute coronary syndrome with percutaneous coronary intervention

Purpose: To measure the adherence and persistence of patients with acute coronary syndrome (ACS) initiating prasugrel after percutaneous coronary intervention (PCI). Methods: Using the Thomson Reuters MarketScan Commercial and Medicare Supplemental database, a retrospective cohort study identified patients initiating prasugrel following ACS-PCI hospitalization in 2009-2011. Prasugrel adherence over 12 months was measured using the medication possession ratio (MPR); predictors of adherence were identified using a logistic regression model. Persistence was defined as time on continuous therapy; a Cox model identified predictors of prasugrel discontinuation. Results: Among 1,340 patients, the mean age was 57 years; 79.5 % were male. Median prasugrel MPR was 93.2 %; 69.0 % of patients had an MPR >= 80 %. Predictors of adherence < 80 % included prior PCI [odds ratio (OR) 0.60; 95 % confidence interval (CI) 0.40-0.90], prior depression (OR 0.37; 95 % CI 0.16-0.84), prior bleeding (OR 0.41; 95 % CI 0.19-0.86), and baseline anticoagulant use (OR 0.13; 95 % CI 0.03-0.55). Baseline statin use predicted higher adherence (OR 1.56; 95 % CI 1.21-2.02). The median duration of prasugrel therapy was 259 days. Predictors of discontinuation included prior anemia [hazard ratio (HR) 1.63; 95 % CI 1.21-2.21], prior cardiomyopathy (HR 2.72; 95 % CI 1.44-5.13), and prior ischemic heart disease (HR 1.15; 95 % CI 1.00-1.32); baseline statin use predicted reduced risk of discontinuation (HR 0.85; 95 % CI 0.75-0.97). Conclusions: Although adherence to prasugrel was generally high, the duration of therapy was frequently below recommendations. An awareness of risk factors for low adherence or early discontinuation can point to appropriate targets for intervention

Validation of claims algorithms for progression to metastatic cancer in patients with breast, non-small cell lung, and colorectal cancer

Background: Validated algorithms for identifying progression to metastatic cancer could permit the use of administrative claims databases for research in this area.Objective: To identify simple algorithms that could accurately detect cancer progression to metastatic breast, non-small cell lung, and colorectal cancer using medical and pharmacy claims data.Methods: Adults with stage I–III breast, non-small cell lung cancer (NSCLC), or colorectal cancer (CRC) in the Geisinger Health System from 2004–2011 were selected. Evidence of progression was extracted via manual chart review as the reference standard. In addition to secondary malignancy diagnosis (ICD-9 code for metastases), diagnoses, procedures, and treatments were selected with clinician input as indicators of cancer progression. Random forests models provided variable importance scores. In addition to codes for secondary malignancy, several more complex algorithms were constructed and performance measures calculated.Results: Among those with breast cancer (17/502 [3.4%] progressed), the performance of a secondary malignancy code was suboptimal (sensitivity: 64.7%; specificity: 86.0%; positive predictive value [PPV]: 13.9; negative predictive value [NPV]: 98.6%); requiring malignancy at another site or initiation of immunotherapy increased PPV and specificity but decreased sensitivity. For NSCLC (61/236 [25.8%] progressed) codes for secondary malignancy alone (PPV: 47.4%; NPV: 84.8%; sensitivity: 60.7%; specificity: 76.6%) performed similarly or better than more complex algorithms. For CRC (33/276 [12.0%] progressed), secondary malignancy codes had good specificity (92.7%) and NPV (92.3%) but low sensitivity (42.4%) and PPV (43.8%); an algorithm with change in chemotherapy increased sensitivity but decreased other metrics.Conclusions: Selected algorithms performed similarly to the presence of a secondary tumor diagnosis code, with low sensitivity/PPV and higher specificity/NPV. Accurate identification of cancer progression likely requires verification through chart review