Index Prescription Research Articles

Adherence, Persistence of Use, and Costs Associated With Second-Generation Antipsychotics for Bipolar Disorder

A retrospective study using Medicaid claims identified patients with bipolar disorder for whom oral second-generation antipsychotics were prescribed and compared rates of adherence, persistence of use, and costs across five groups of patients taking aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone. Medicaid claims data for 2,446 bipolar patients were analyzed from eight states. The 18-month observation period included the six months before and the 12 months after the index prescription date. Adherence was defined as a medication possession ratio >80%. Persistence of use was measured by the number of days of medication therapy before a 30-day gap. Mental health-related prescription costs, total prescription costs, total mental health-related costs, and total costs were assessed. Ziprasidone was the comparator. Clinically recommended doses of second-generation antipsychotic medications were prescribed for 45% of the patients (N = 1,102). Of these, 58% (N = 642 of 1,102) were adherent with the prescribed medication, with no significant differences between medication groups. Median time to nonpersistence of use averaged 96 days. Patients taking olanzapine were about 35% more likely than patients taking ziprasidone to discontinue taking their medication (hazard ratio = 1.34, 95% confidence interval = 1.02-1.76, p = .04). Mental health-related prescription costs and total prescription costs were lower for risperidone than ziprasidone. No statistically significant differences were found between the groups for all mental health-related costs or total costs. Among patients in a sizeable Medicaid cohort for whom a second-generation antipsychotic medication was prescribed, less than half had a clinically recommended dose, and less than two-thirds with a clinically recommended dose were adherent to the medication, confirming that many patients with bipolar disorder do not receive clinically recommended doses of second-generation antipsychotics.

Prevalence and detection rate of underlying disease in men with erectile dysfunction receiving phosphodiesterase type 5 inhibitors in the United Kingdom: a retrospective database study

To determine the rate of newly detected underlying disease in men receiving their first (index) phosphodiesterase type 5 inhibitor (PDE5i) prescription. This non-interventional, retrospective study used anonymised patient records from UK general practices identified from the THIN database. Records of men aged ≥ 18 years, who received an index PDE5i prescription between January 1999 and June 2008 and with a continuous medical history (≥ 60 months) before the index prescription were included. Primary end-points were the prevalence of underlying disease prior to the index prescription and to establish the detection rate, defined as cumulative incidence of such a diagnosis in the 3 months following the index prescription. Assessments included comparison with age-matched controls, comparison with identical time periods immediately before and 1 year after, index prescription, and changes over time during the study period. Descriptive statistics, analysis of proportions and multivariate logistic regression analysis were used. Among the 24,708 patients receiving a PDE5i, the prevalence of any underlying diagnosis before the index prescription was 70.23%; prevalence of vasculogenic disease was highest (48.20%). The detection rate of any underlying disease was 11.53%, and again highest for vasculogenic disease (4.07%). Compared with an age-matched control population, the additional detection rate of an unknown underlying disease at PDE5i prescription was 45 for hypertension, 61 for hypercholesterolaemia, 38 for diabetes and 5 for hypogonadism per 10,000 men. Only a minority of men with erectile dysfunction have a previously undiagnosed important underlying disease that is uncovered at the time of an initial PDE5i prescription by a GP.

Prescription Patterns in Asthma Patients Initiating Salmeterol in UK General Practice

An association between salmeterol, a long-acting β(2)-agonist (LABA), use and rare serious asthma events or asthma mortality was observed in two large clinical trials. This has resulted in heightened scrutiny of LABAs and comprehensive reviews by regulatory agencies. The aim of this retrospective observational cohort study was to better characterize salmeterol medication use patterns in the UK. We describe asthma prescription patterns in a cohort of patients (n =17,745) in the General Practice Research Database who initiated treatment with salmeterol-containing prescriptions between 2003 and 2006, including salmeterol and salmeterol/fluticasone propionate in a single device. Prescriptions patterns by medication class, including concurrent prescription of salmeterol with inhaled corticosteroids (ICS), were described using 6-month intervals in the 1-year period before and after the salmeterol-containing index prescription. In the 0- to 6-month and 7- to 12-month periods prior to initiation of the salmeterol-containing prescription, the cohort experienced worsening of asthma, measured by an increase in the proportion of patients with prescriptions for short-acting β-agonists [SABA] (73-89%), ICS (70-81%) and systemic corticosteroids (14-28%). Nearly all patients prescribed salmeterol were concurrently prescribed ICS (≥95% within 90 days). In the 12 months following initiation of the salmeterol-containing prescription, a decrease in asthma prescriptions was observed. These results support the appropriate prescribing of salmeterol-containing medications, as per recommendations in asthma treatment guidelines in the UK. Salmeterol was consistently prescribed as an add-on asthma-controller with an ICS for most patients, and was associated with improvements in asthma control, as indicated by decreases in SABA and systemic corticosteroid prescriptions following salmeterol introduction.

Time to discontinuation of first- and second-generation antipsychotic medications in the treatment of schizophrenia

Background Continuous adherence to antipsychotic treatment is critical for individuals with schizophrenia to benefit optimally, yet studies have shown rates of antipsychotic discontinuation to be high with few differences across medications. We investigated discontinuation of selected first- and second-generation antipsychotics among individuals with schizophrenia receiving usual care in a VA healthcare network in the U.S. mid-Atlantic region. Methods We identified 2138 VA patients with schizophrenia who initiated antipsychotic treatment with one of five non-clozapine second-generation antipsychotics or either of the two most commonly prescribed first-generation agents between 1/2004 and 9/2006. The dependent variable was duration of continuous antipsychotic possession from the index prescription until the first gap of more than 45 days between prescriptions. We used the Cox proportional hazards model to compare the hazard of discontinuation among the seven antipsychotics controlling for patient demographic and clinical characteristics. The reference group was olanzapine. Results The majority of patients (84%) discontinued their index antipsychotic during the follow-up period (up to 33 months). In multivariable analysis, only risperidone had a significantly greater hazard of discontinuation compared to olanzapine (Adjusted hazard ratio = 1.15, 95% CI: 1.02–1.30, p = .025). Younger age, non-white race, homelessness, substance use disorder, recent inpatient mental health hospitalization, and prescription of another antipsychotic were also associated with earlier discontinuation. Conclusions Examination of a usual care sample of individuals with schizophrenia revealed short durations of antipsychotic use, with only risperidone having a shorter time to discontinuation than olanzapine. These findings demonstrate that current antipsychotic agents have limited overall acceptability by patients in usual care.

Cost-effectiveness of enhancing adherence to therapy with statins in the setting of primary cardiovascular prevention. Evidence from an empirical approach based on administrative databases

Aim To estimate the cost-effectiveness of enhancing adherence to statin therapy across a large population without signs of pre-existing cardiovascular disease. Methods and results The cohort of 84,262 patients aged 40–79 years, resident in the Italian Lombardia Region, who were newly treated with statins during 2002–2003, was followed from index prescription until 2007. During follow-up the 1397 patients who experienced a hospitalization for ischemic heart disease (IHD) were identified (outcome). Adherence from index prescription until the date of hospitalization or censoring was measured by the proportion of days covered by the therapy with statins (PDC). Cost-effectiveness of enhancing adherence was measured through the incremental cost-effectiveness ratio (ICER). The robustness of findings was tested in a sensitivity analysis. Interventions to increase the average level of adherence from 45% (baseline) to 50% (“soft” intervention) or to 90% (“hard” intervention) reduced the number of patients who experience IHD (from 38.9 to 38.4 or 35.8 events every 10,000 person-year, respectively), and increased the cost for drug therapy (from 1326 to 1452 or 2626 thousand euros every 10,000 person-year, respectively). ICER ranged from 243 (95% CI: 230–259) to 413 (391–439) thousand euros every 10,000 person-year for the soft and hard interventions, respectively. Conclusions Interventions aimed at enhancing adherence to statin therapy in the setting of primary cardiovascular prevention might offer important benefits in reducing the risk of cardiovascular outcome, but at a substantial cost.

Relationship between physician specialty and allopurinol prescribing patterns: a study of patients with gout in managed care settings

Objective:Allopurinol is used to lower serum uric acid (sUA) levels in gout patients. The objective of this study was to investigate the influence of physician specialty on allopurinol treatment patterns and sUA control.Design and methods:This was a retrospective study using claims from a managed care database of US health plan enrollees. Gout patients at least 18 years of age who received allopurinol were identified from the database between January 1, 2002 and April 30, 2007. The index date was defined as the date of the earliest allopurinol claim, and patients were required to have health plan enrollment for at least 365 days prior to and following the index date for inclusion. Physician specialty was determined using the index allopurinol claim. Dosage of allopurinol prescription(s) and number of gout flares were determined from claims data. sUA measurements were used to assess goal attainment over a period of at least one year following the index allopurinol prescription.Results:There were 3363 patients with gout of whom 69.9% received an index allopurinol prescription from a generalist/internist, 5.7% from a rheumatologist, 2.6% from a nephrologist, and 21.8% from a physician with other specialty. Of patients receiving their index prescription from a nephrologist, 38.7% reached the sUA goal of <6 mg/dL (357 μmol/L), as compared to patients prescribed by a rheumatologist, generalist/internist, or other physician (35.4%, 31.4%, and 39.4%, respectively; P = 0.015). When controlling for patient characteristics, multivariate analysis did not reveal statistically significant different odds of sUA goal attainment based on prescribing physician specialty, though separate analyses indicated that patients prescribed by a nephrologist had fewer gout flares. Change in allopurinol dosage from initial to final dose was more frequent among patients prescribed by rheumatologists and nephrologists.Conclusion:There is significant heterogeneity in the specialists’ management of sUA levels in patients with gout, possibly reflecting differences in case mix and treatment approaches. Limitations related to the use of claims data, such as inability to observe medications filled over-the-counter, should be considered when interpreting study results.

Better compliance to antihypertensive medications reduces cardiovascular risk

The effect of compliance with antihypertensive medications on the risk of cardiovascular outcomes in a population without a known history of cardiovascular disease has been addressed by a large population-based prospective, cohort study carried out by linking Italian administrative databases. The cohort of 242 594 patients aged 18 years or older, residents in the Italian Lombardy Region, who were newly treated for hypertension during 2000-2001, was followed from index prescription until 2007. During this period patients who experienced a hospitalization for coronary or cerebrovascular disease were identified (outcome). Exposure to antihypertensive drugs from index prescription until the date of hospitalization or censoring was assessed. Proportional hazards models were fitted to assess the association between persistence on and adherence with antihypertensive drug therapy and outcome. Data were adjusted for several covariates. During an average follow-up of 6 years, 12 016 members of the cohort experienced the outcome. Compared with patients who experienced at least one episode of treatment discontinuation, those who continued treatment had a 37% reduced risk of cardiovascular outcomes (95% confidence interval 34-40%). Compared with patients who had very low drug coverage (proportion of days covered ≤ 25%), those at intermediate (from 51 to 75%) and high coverage (>75%) had risk reductions of 20% (16-24%) and 25% (20-29%), respectively. Similar effects were observed when coronary and cerebrovascular events were considered separately. In the real life setting, fulfillment compliance with antihypertensive medications is effective in the primary prevention of cardiovascular outcomes.

Impact of Duration of Antidepressant Treatment on the Risk of Occurrence of a New Sequence of Antidepressant Treatment

Despite the recommendation that antidepressant treatment should be continued for several months to reduce the risk of relapse/recurrence of depression, early discontinuation is frequent in naturalistic conditions. The study was aimed at exploring the impact of early discontinuation of antidepressant treatment on the risk of antidepressant re-initiation. A follow-up study of persons (n=35,053) starting antidepressant treatment was performed using a representative sample of the French Social Security Insurance national database. The risk of re-initiation of antidepressant treatment was higher if the duration of the index episode of antidepressant treatment was ≥ 6 months [hazard ratio (HR)=2.35; 95% CI 2.25-2.45) or 2-5 months (HR=1.65; 95% CI 1.59-1.71) compared to ≤ 1 month. The other characteristics independently associated with re-initiation of treatment were older age, female gender, low income, serious chronic illness, index prescription by a specialist and co-prescription of other psychotropic drugs. The lower risk of re-initiation of antidepressant treatment in persons with shorter-than-recommended duration of antidepressant treatment might be explained by overprescription of antidepressants in persons with sub-threshold symptoms.

Impact of Treatment Success on Health Service Use and Cost in Depression

Research has consistently demonstrated a relationship between depression and increased levels of health service use over the short term. However, much less is known about how this relationship is influenced by the success, or otherwise, of depression management strategies, and the economic impact over the longer term. To investigate the economic impact of non-remission on health service use and costs over 12 months from the index episode in patients with depression. A naturalistic, longitudinal study was carried out using data from a large primary care UK general practice research database between 2001 and 2006. The records of 88 935 patients aged ≥18 years, diagnosed with depression and in receipt of at least two antidepressant prescriptions (for amitriptyline, citalopram, escitalopram, fluoxetine, paroxetine, sertraline or venlafaxine) in the first 3 months after the index prescription were included. The main outcome measures were health service use and cost over the 12-month study period, by remission status, where remission is defined as patients not using antidepressants for at least 6 months after antidepressant treatment has ended. Sociodemographic and clinical characteristics were similar for participants classified as in remission and those not in remission. Over 12 months from the index prescription, patients classified as non-remitters spent longer, on average, than patients classified as remitters on concomitant psychotropic medication (204 days vs 93 days, respectively), and had more contact with primary care services (17 vs 13 GP visits), secondary care psychiatrists and other specialists (47% vs 40%). Days in hospital, accident and emergency attendances and psychological therapy contacts did not differ between the groups. Total 12-month costs per participant were significantly lower for remitters (mean £656 vs £937; mean difference £317; p < 0.0001). Total costs fell over time for both groups, but at a faster rate for those in remission, and for those who remitted earlier after the index prescription than for those who remitted later. Successful cessation of antidepressant medication treatment in adults with depression can result in significant cost savings to the health service.

Using primary care prescribing databases for pharmacovigilance.

In the UK, adverse drug reactions (ADRs) are responsible for over 6.5% of all hospital admissions, representing a significant morbidity and cost burden to the health service. We aimed to develop an ADR monitoring system capable of identifying the reasons for patient discontinuation of drug therapy within 6 months of the index prescription. Patients first prescribed amlodipine between 1 March 2004 and 28 February 2007 who discontinued their amlodipine medication within 6 months of the index prescription were identified from the practice team information (PTI) database. Once identified, reasons for amlodipine discontinuation were assessed by an electronic database search using relevant Readcodes and key words and by a direct approach to the primary care medical records. The PTI database identified 995 patients [61.4% females, mean age 65.9 years (SD 12.4 years)] who discontinued amlodipine within 6 months of an index prescription. An electronic search of the database, using Readcodes, identified that 19.4% (193) of patients who discontinued their medication had an ADR recorded in the database. Six (20%) of 30 participating primary care practices, contributing to the PTI database, agreed to be approached directly and supply the reasons for discontinuation for the 51 patients identified as having discontinued amlodipine in their practices. Completed data were returned for all 51 patients, 98% of whom discontinued amlodipine due to an ADR or adverse drug event. The results of this study confirm that primary care prescribing databases can be easily used to identify the frequency and nature of ADRs occurring in an ADR-enriched population identified through medication discontinuation.

Medication Adherence and Hospitalization Among Patients With Schizophrenia Treated With Antipsychotics

This analysis assessed rates of medication adherence and predictors of nonadherence and hospitalization among patients treated with long-acting injectable and oral antipsychotic therapies. Data were from a retrospective analysis of Florida Medicaid recipients with schizophrenic disorder (ICD-9-CM code 295.XX) who received a prescription for an antipsychotic between July 1, 2004, and June 30, 2005. Patients were required to have filled one additional antipsychotic prescription during follow-up. Adherence measures included medication possession ratio (MPR), medication persistence, medication consistency, and maximum gap in treatment. Multivariate logistic regression models identified predictors of nonadherence and hospitalization. Patients were considered adherent if they had an MPR ≥ .8. A total of 12,032 patients met selection criteria. The mean ± SD MPR was .79 ± .23, medication persistence was 94.1% ± 16.4%, medication consistency was 83.3% ± 16.4%, and the maximum gap in treatment was 29.7 ± 41.4 days. Thirty-seven percent of patients were hospitalized for any cause, and 32% had a psychiatric hospitalization. Predictors of nonadherence included newly starting treatment; younger age; a substance abuse diagnosis; use of a mood stabilizer, antidepressant, anxiolytic, or anticholinergic; and receipt of long-acting first-generation antipsychotics. Receipt of long-acting second-generation therapy or receipt of both first- and second-generation medications was associated with lower likelihood of nonadherence. Predictors of hospitalization risk included a diagnosis of other psychoses or substance abuse, anticholinergic use, and nonadherence to therapy. Results document rates of antipsychotic adherence and predictors of nonadherence and hospitalization. Findings may be useful to health plan administrators, formulary decision makers, and physicians.

Dose Adjustment and Treatment Interruptions Associated with Second-Line Nilotinib or Dasatinib In Real-World Treatment of Chronic Myeloid Leukemia

AbstractAbstract 4758 Background:Nilotinib and dasatinib are second-generation tyrosine kinase inhibitors (TKI) indicated for the treatment of chronic phase (CP) and accelerated phase (AP) Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) patients resistant to or intolerant of first-line therapy with imatinib. Dasatinib is also indicated for treatment of blast crisis (BC) patients. The recommended dose of nilotinib for treatment of resistant or intolerant Ph+ CML-CP is 400 mg twice daily. The current recommended starting dose of dasatinib for second-line therapy of Ph+ CML-CP is 100 mg once daily, and for Ph+ CML-AP or BC is 140 mg once daily. Some patients may experience treatment-related adverse events at the recommended doses of nilotinib or dasatinib, necessitating a dose reduction or interruption of treatment. Therefore, patients may not be receiving the full approved therapeutic doses. There is no available information comparing dose modifications or interruption of treatment between nilotinib and dasatinib. The objective of this study was to compare the frequency of dose adjustments and treatment interruptions between nilotinib and dasatinib in second-line therapy in CML patients from a clinical practice setting perspective. Methods:Two claims databases were combined (MarketScan and Ingenix Impact, 01/2002-12/2008) to identify patients diagnosed with CML (ICD-9 code 205.1x) and who had received ≥1 prescription of nilotinib or dasatinib. Patients were required to have continuous enrollment ≥1 month prior to and after the index date. The index date was defined as the first prescription for nilotinib or dasatinib. Two patient cohorts were created based on patient's index treatment. Dasatinib data prior to the 100 mg once daily approval date were excluded from the analysis. Patients were followed for up to 6 months from the index date to the earliest of the termination of health care plan enrollment, or end of data availability. Dosage characteristics, including any dose changes from index prescription, defined as either an increase or decrease in the delivered dose and average dose were calculated during the study period. A ≥15% dose decrease in average dose is selected for comparison between the two groups as it is the mean of the lowest absolute dose change. Dose adjustments were further characterized in relation to the incidence and frequency of hematological and non-hematological events during the study period. Results:Data were analyzed for 514 patients receiving a second-line TKI (67 nilotinib, 447 dasatinib). Baseline characteristics were similar between the groups. Seven patients (2 nilotinib, 5 dasatinib) were excluded due to missing dosage information. Patients treated with dasatinib had more follow-up days in the study period than nilotinib-treated patients (mean ± standard deviation [SD], 162 ± 39 days versus 143 ± 51 days; P = 0.0003). There were no differences between the number of patients treated with nilotinib or dasatinib who had any dose adjustments over the study period (P = 0.8424). Stratification of the data by percent of adjustment revealed statistically significant differences between the two treatment groups. Eighty-nine (19.9%) patients treated with dasatinib had at least one dose reduction of at least 15% compared with 4 patients (6.0%) treated with nilotinib (P = 0.0057). Dasatinib-treated patients with at least 15% dose reduction experienced a mean ± SD of 0.24 ± 0.52 dose decreases compared with 0.06 ± 0.24 dose decreases for patients who received nilotinib (P = 0.0055). However the time to first dose reduction was longer for dasatinib users than for nilotinib users (15.1 ± 37.5 days vs. 7.5 ± 31.5 days, P = 0.0194). Dose decreases occurred within 30 days of a hematological or non-hematological event in 49.5% of patients. Conclusion:These data demonstrate that more CML patients treated second-line with dasatinib experienced dose reductions of at least 15% than patients treated second-line with nilotinib, and that fewer dose reductions were required by the nilotinib users. Although this study did not assess the specific reasons for dose change, dose reductions are frequently associated with hematological or non-hematological events. Future studies may also investigate the relationship between response to treatment and dose reduction for the two TKIs. Disclosures:Yu:Analysis Group, Inc.: Employment. Guerin:Analysis Group, Inc.: Employment. Bollu:Novartis: Employment. Cloutier:Analysis Group, Inc.: Employment. Williams:Novartis: Employment, Equity Ownership.

The Epidemiology of Prescriptions Abandoned at the Pharmacy

Picking up prescriptions is an essential but previously unstudied component of adherence for patients who use retail pharmacies. Understanding the epidemiology and correlates of prescription abandonment may have an important effect on health care quality. To evaluate the rates and correlates of prescription abandonment. Cross-sectional cohort study. One large retail pharmacy chain and one large pharmacy benefits manager (PBM) in the United States. Prescriptions bottled at the retail pharmacy chain between 1 July 2008 and 30 September 2008 by patients insured by the PBM were identified. Pharmacy data were used to identify medications that were bottled and either dispensed or returned to stock (RTS) or abandoned. Data from the PBM were used to identify previous or subsequent dispensing at any pharmacy. The first (index) prescription in a class for each patient was assigned to 1 of 3 mutually exclusive outcomes: filled, RTS, or RTS with fill (in the 30 days after abandonment, the patient purchased a prescription for a medication in the same medication class at any pharmacy). Outcome rates were assessed by drug class, and generalized estimating equations were used to assess patient, neighborhood, insurance, and prescription characteristics associated with abandonment. 10 349 139 index prescriptions were filled by 5 249 380 patients. Overall, 3.27% of index prescriptions were abandoned; 1.77% were RTS and 1.50% were RTS with fill. Patients were least likely to abandon opiate prescriptions. Prescriptions with copayments of $40 to $50 and prescriptions costing more than $50 were 3.40 times and 4.68 times more likely, respectively, to be abandoned than prescriptions with no copayment (P < 0.001 for both comparisons). New users of medications had a 2.74 times greater probability of abandonment than prevalent users (P < 0.001), and prescriptions delivered electronically were 1.64 times more likely to be abandoned than those that were not electronic (P < 0.001). The study included mainly insured patients and analyzed data collected during the summer months only. Although prescription abandonment represents a small component of medication nonadherence, the correlates to abandonment highlight important opportunities to intervene and thereby improve medication taking. CVS Caremark.

Triptan persistency among newly initiated users in a pharmacy claims database

Our study was conducted to describe prescription refill patterns among patients newly treated with triptans. Although triptans are efficacious in treating migraine headache, the persistency of triptan use among newly initiated users has not been well described. From a US pharmacy claims database, we identified patients receiving new triptan monotherapy prescriptions from 2001 to 2005. Prescription refill information was gathered for two years for each patient. Persistency was defined as sustained refills of the index triptan prescription, regardless of duration between refills. Of 40,892 patients receiving a new triptan prescription, 53.8% (N = 22031) did not persistently refill their index triptan. Of these, 25.5% discontinued prescription migraine therapy, 7.4% switched to a different triptan, and 67.1% switched to a non-triptan migraine medication at the time of their first refill. Only 46.2% of patients received at least one persistent refill. Migraine patients were more likely to discontinue their triptan after their index prescription than at any other time in their prescription refill history. The majority of patients did not persistently refill triptans, but filled prescriptions for non-specific migraine therapies such as opioids and non-steroidal anti-inflammatory drugs. Reasons for triptan discontinuation warrant further investigation.

Epidemiologic study of aripiprazole use and the incidence of suicide events

Because second generation antipsychotics (SGA) might affect the risk of suicide, systematic assessment of suicide risk associated with SGA in the postmarketing setting is important and of interest to regulatory authorities. To fulfill a postmarketing request, our objective was to determine suicide event (attempted or completed) incidence in patients with schizophrenia or bipolar disorder, prescribed aripiprazole. Using administrative data from three US sources, we assessed study endpoints of suicide attempts and death by suicide in patients aged ≥18 enrolled continuously for ≥3 months in their health plans before receiving their first ever antipsychotic (November 2002-December 2005). Among 20 489 antipsychotic users (8985 patient-years), unadjusted suicide event rates (per 1000 patient-years) were: 20.69 (aripiprazole); 23.99 (olanzapine); 32.33 (quetiapine); 19.69 (risperidone); 48.52 (ziprasidone). Compared with current users of other SGA combined, aripiprazole users did not have an increased risk of suicide events (crude hazard ratio (HR) = 0.79, 95%CI: 0.48-1.30; adjusted HR = 0.69, 95%CI: 0.42-1.14-(controlling for study site, age, sex, index prescription year, antipsychotic use history, other pharmacotherapy exposure, comorbidity presence, schizophrenia/bipolar disorder, suicide attempts, number inpatient/outpatient encounters). In this large, multi-site study, compared with other SGA combined, aripiprazole is not associated with an increased risk of suicide events in an inception cohort of patients with ICD-9/ICD-10 codes indicative of schizophrenia or bipolar disorder.

Linear Accelerator-based Stereotactic Radiosurgery for Single Brainstem Metastases: The Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) Experience

To review the safety and efficacy of linear accelerator-based stereotactic radiosurgery (SRS) for single brainstem metastases. We reviewed all patients with brain metastases treated with SRS at DF/BWCC from 2001-2009 to identify patients who had SRS to a single brainstem metastasis. Overall survival and freedom-from-local-failure rates were calculated from the date of SRS using the Kaplan-Meier method. Prognostic factors were evaluated using the log-rank test and Cox proportional hazards model. A total of 24 consecutive patients with brainstem metastases had SRS. All had single lesions in the brainstem (10 midbrain, 13 pons and 1 medulla). At the time of SRS, 21/24 had metastatic lesions elsewhere within the brain. 23/24 had undergone previous whole-brain radiotherapy. Primary diagnoses included 8 NSCLC, 8 breast cancer, 3 melanoma, 3 renal cell carcinoma and 2 others. Median dose was 13 Gy (range, 8-16). One patient had fractionated SRS 5 Gy x 5. Median target volume was 0.2 cc (range, 0.02-2.39). At least 98% of the target was covered by the prescription dose in all cases. Median normalization was 73% (range, 52-90). Median conformity index (prescription isodose volume/PTV) and homogeneity index (maximum dose/prescribed dose) were 1.81 (range, 1.36-2.60) and 1.39 (range, 1.22-1.92), respectively. Fourteen patients were female (58%). The median age was 57 years (range, 42-92). Follow-up information was available in 22/24 cases. At the time of analysis, 18/22 patients (82%) had died. The median overall survival was 5.3 months (range, 0.8-21.1 months). The 4 surviving patients have been followed for 5, 8, 14, and 21 months. The only prognostic factor that trended toward statistical significance for overall survival was the absence of synchronous brain metastasis at the time of SRS (1-year overall survival 31% with vs. 67% without synchronous brain metastasis, log-rank p = 0.11). Non-significant factors included primary tumor histology and status of extracranial disease (progressing vs. stable/absent). Local failure occurred in 4/22 cases. Actuarial freedom-from local failure for all cases was 78.6% at 1 year. RTOG grade 3 toxicities were recorded in two patients (ataxia, confusion). Both patients progressed at distant sites within the brain. Linac-based SRS for small-volume brainstem metastases using a median dose of 13 Gy is associated with acceptable local control and low morbidity.

Comparison Study of Intensity Modulated Arc Therapy (IMAT) using Single or Multiple Arcs to Intensity Modulated Radiation Therapy (IMRT) for High-risk Prostate Cancer

IMAT is a complex form of IMRT that allows dose delivery in a single or multiple arcs. The treatment of nodal stations in high-risk prostate cancer is controversial, however, there is emerging data to support enhanced biochemical disease free survival with nodal irradiation. We compared the plan quality and plan efficiency of IMRT versus one arc (1Arc) versus three arcs (3Arc) for treatment of high-risk prostate cancer. Fifteen patients with high-risk prostate cancer as defined by NCCN, were studied. Prostate (PTVp), right pelvic lymph nodes (PTVrln), left pelvic lymph nodes (PTVlln), and organs at risk were contoured. The total planned dose was 79.20Gy/1.8Gy/fraction. PTVp, PTVrln, PTVlln received 50.40Gy/1.8Gy/fraction followed by a boost to PTVb of 28.80Gy. Three plans were generated for each patient: 7 beams IMRT, 1Arc (1full rotation, 1 isocenter), 3Arc (1 full, 2 partial rotations for the lymph nodes, 3 isocenters) using Rapid Arc technology. All 3 plans were calculated to maintain Dmax ≤110% with 95% coverage to PTVt (PTVp+PTVrln+PTVlln). All plans were optimized using the same dose constraints. Nine patients were treated using 3Arc technique, 4 with IMRT and 3 using 1Arc. All plans had excellent coverage, i.e., 95% of dose to 95% of PTVt. The average RTOG conformity index (prescription volume/target volume), was 1.17, 1.20, 1.15 for IMRT, 1Arc, 3Arc, respectively, with 3Arc exhibiting the highest conformity. The 3 plans' homogeneity index was within 1% of each other. Similarly, Dmean of bladder was within 2% of each other. The lowest mean dose for the rectum was achieved with the IMRT plan, with 10% lower dose than the arc plans. The Paddick gradient index (50% isodose volume/prescription volume) of the 3Arc was superior to IMRT by 27.4% (p = 0.006). The average monitor unit (MU) was highest in the IMRT plan (1685) versus 1Arc (575) versus 3Arc (1079), (p =0.0001 for 1arc). The average beam on time was 6 minutes for IMRT compared to IMAT, p = 0.001. The beam on time of the arc therapies was 1.3 and 2.9 minutes for 1Arc and 3Arc, respectively. Intensity Modulated Arc Therapy delivers acceptable coverage compared to IMRT for high-risk prostate cancer, it also has the potential to achieve a more favorable dose gradient profile, conformity, lower MU and beam on time compared to IMRT. The 3Arc plan proved to have a superior gradient and conformity indices in contrast to the 1Arc plan. In regards to dose to organs at risk, there was no significant difference except that a lower rectal dose was seen in the IMRT plans.

Costs of Gastrointestinal Events after Outpatient Opioid Treatment for Non-Cancer Pain

Gastrointestinal (GI) adverse effects are common with oral opioid treatment. To estimate the costs associated with GI events after oral short-acting opioid treatment, from the payer perspective. Medical and pharmacy claims from the PharMetrics' Patient-Centric Database were used to identify opioid-naïve patients who received a new prescription for oxycodone- or hydrocodone-containing immediate-release oral products between 2002 and 2006. Health-care resource use and costs were determined for patients with claims associated with ICD-9 CM (International Classification of Diseases-9th Clinical Modification) codes for nausea/vomiting (787.0x), constipation (564.0x), bowel obstruction (560, 560.1, 560.3, 560.39, 564.81), or antiemetic and laxative prescriptions during the 3 months after opioid index prescription and compared with patients without these GI event medical or prescription claims. Resource use data were compared using negative binomial regression and cost data were compared using ordinary least squares confirmed by generalized gamma regression analysis while controlling for demographics, treatment duration, and comorbidities. Data from 237,447 patients were analyzed. Patients with GI event claims had significantly more hospitalizations (adjusted mean 0.20 to 0.97 vs 0.17, respectively, p < 0.001), days in the hospital (1.12 to 12.05 vs 1.00 days, p < 0.001), emergency department visits (0.36 to 1.44 vs 0.25 visits, p < 0.001), outpatient office visits (5.68 to 11.81 vs 4.11 visits, p < 0.001), and prescription claims (7.46 to 8.21 vs 6.06 claims, p < 0.001) than did patients without any GI event claims in the 3 months after index opioid prescription. Compared with patients without any GI event claims, incremental adjusted mean total health-care costs for patients with any of the GI event claims ranged from $4,880 to $36,152 and were significant (p < 0.001). The economic burden of GI events coincident with opioid treatment is significant for patients with a GI event recorded in claims. Reducing GI adverse effects has potential cost savings for the health-care system.

Results of a retrospective database analysis of adherence to statin therapy and risk of nonfatal ischemic heart disease in daily clinical practice in Italy

Background: Previous studies have reported that statin use was associated with reductions in cardiovascular morbidity and mortality among patients with dyslipidemia, even without established cardiovascular disease. However, inadequate adherence may reduce statins' protective effects. Objective: The aim of this work was to investigate whether an association exists between statin adherence when used as primary prevention and risk of subsequent ischemic heart disease (IHD). Methods: People aged ≥18 years who were residents of Italy's Lombardy region and were newly treated with statins in 2002 to 2003 were assessed as part of a retrospective analysis of data from a healthservices database. Patients who were hospitalized for IHD during this period were identified with hospitaldischarge information from a health-services database; IHD-related hospitalizations were identified by International Classification of Diseases, Ninth Revision, Clinical Modification, codes for acute myocardial infarction (410), acute and subacute forms of IHD (411), and/or codes concerning coronary revascularization (36.0–36.9). Four groups of patients were excluded: those with ≥1 lipid-lowering drug within 2 years before the index prescription (to limit the sample to treatment initiators); those who had been hospitalized for cardiovascular disease or had used medications for IHD or heart failure within 2 years before the index date (to limit the study to primary prevention); those who did not have ≥1 year of follow-up; and those who received only 1 dispensation of a statin during the first year after the index prescription. Follow-up continued until hospitalization for IHD or any other cardiovascular cause, death from any cause, emigration, or the end of the study period (June 30, 2007). The proportion of days covered (PDC) by therapy with statins was the exposure variable; it served as a proxy for adherence. PDC (and therefore adherence) was categorized as very low (≤25%), low (26%–50%), intermediate (51%–75%), or high (≥75%) coverage. A proportional hazards model was fitted to estimate hazard ratio (HR) and 95% CIs for the association between time-dependent categories of PDC and time of IHD hospitalization, after correcting for covariates. Results: A group of 90,832 patients was included; during follow-up, 1480 patients experienced a hospitalization for IHD. After the Cox proportional hazards model was adjusted for age, sex, type of statin dispensed at index prescription, current use of other selected drugs (ie, antidiabetics, antihypertensives, digitalis or organic nitrates, or other cardiac medications), Charlson comorbidity index, and whether or not a given patient switched statins, those with low, intermediate, or high statin coverage had HR (95% CI) values of 0.85 (0.72–0.98), 0.82 (0.71–0.95), and 0.81 (0.71–0.94), respectively, compared with patients with very low coverage. Conclusions: In these Italian subjects without a history of cardiovascular disease, low, intermediate, and high levels of adherence to statin pharmaco-therapy were associated with lower risk of nonfatal IHD compared with those who had very low (≤25%) adherence. However, these findings have several limitations, such as the use of database information (rather than medical records), the assumption that PDC accurately represented actual adherence, and confounding (ie, unmeasured factors related to PDC or to adherence may have influenced clinical outcomes).

Weighing Scientific Evidence: Let's Keep the Blindfold Off

Back to table of contents Next article Taking IssueFull AccessWeighing Scientific Evidence: Let's Keep the Blindfold OffBonnie T. Zima M.D., M.P.H.,Bonnie T. Zima M.D., M.P.H.Search for more papers by this author,Published Online:1 Feb 2010https://doi.org/10.1176/ps.2010.61.2.107AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Lady Justice—or Justitia, the Roman goddess of justice—holds a double-edged sword in her right hand and a scale in her left, and sometimes she is blindfolded. The blindfold symbolizes the ideal of weighing evidence with impartiality. However, in the case of scientific evidence, scrutiny and deliberation are required to find the balance point in measuring the strength of evidence and its applicability to a clinical decision.The findings of a study reported in this issue, "Evidence-Based Use of Second-Generation Antipsychotics in a State Medicaid Pediatric Population, 2001–2005," require careful scrutiny because they could be misinterpreted as indicating overuse or inappropriate use of these agents to treat children. Conclusions about the appropriateness of medication treatment that are based on claims data are limited because the validity of the diagnosis cannot be established from such data and the clinical rationale for prescribing a particular drug is missing. The authors of the report acknowledge that they were unable to link the diagnoses recorded in the Medicaid claims to the index prescription of the antipsychotic.Nevertheless, on the basis of the design and sample size of published studies and diagnoses from claims data, these investigators rated the strength of evidence for each initial prescription of a second-generation antipsychotic for 11,700 children between 2001 and 2005. During this period none of these agents were approved for pediatric use by the Food and Drug Administration (FDA), and the majority of published reports that included children were open-label studies involving risperidone. One medication, aripiprazole, was approved for adult use in November 2002. Was the study premature to apply ratings of evidence strength? Or by applying the ratings at a time when the evidence base was not strong, did the study simply reflect the fact that prescribers were exercising their clinical judgment in making medication decisions for high-risk children?Either way, the study illuminates the larger debate about what constitutes substantial evidence of the safety and effectiveness of psychotropic medications prescribed to children. In 1962 the proposed FDA criterion for "substantial evidence" of effectiveness was "at least two adequate and well-controlled studies, each convincing on its own, to establish effectiveness." With the FDA Modernization Act of 1997, the criterion was relaxed to "one adequate and well-controlled clinical investigation and confirmatory evidence," and rules were revised to allow for extrapolation from adult efficacy data to pediatric patients. National efforts have also been made to standardize approaches to rating scientific evidence. These approaches acknowledge a subjective component in the assessment of research methods to "weigh" scientific evidence. Given the need for more long-term studies to establish the safety and efficacy of antipsychotics for children in real-world settings, let's keep Lady Justice's blindfold off during our deliberations.UCLA-Semel Institute for Neuroscience and Human Behavior FiguresReferencesCited byDetailsCited ByLetterPrathamesh Pathak, M.S., B.Pharm.Donna West, Ph.D.Bradley C. Martin, Pharm.D., Ph.D.1 March 2010 | Psychiatric Services, Vol. 61, No. 3LetterMuhamad Aly Rifai, M.D.1 March 2010 | Psychiatric Services, Vol. 61, No. 3LetterOurania K. Kakisi, M.D.Drosos E. Karageorgopoulos, M.D.Matthew E. Falagas, M.D., D.Sc.1 March 2010 | Psychiatric Services, Vol. 61, No. 3LetterHerng-Ching Lin, Ph.D.Ling-Yu Yang, M.A.Wen-Ta Chiu, M.D.1 March 2010 | Psychiatric Services, Vol. 61, No. 3LetterJonathan D. Brown, Ph.D., M.H.S.Ellen Singer, M.A.Henry T. Ireys, Ph.D.1 March 2010 | Psychiatric Services, Vol. 61, No. 3 Volume 61Issue 2 February, 2010Pages 107-107PSYCHIATRIC SERVICES February 2010 Volume 61 Number 2 Metrics PDF download History Published online 1 February 2010 Published in print 1 February 2010