Risk of Overdose with Exposure to Prescription Opioids, Benzodiazepines, and Non-benzodiazepine Sedative-Hypnotics in Adults: a Retrospective Cohort Study.

BACKGROUND: Concurrent use of benzodiazepines in opioid users has been linked to a higher risk of an emergency room visit or inpatient admission for opioid overdose and death from drug overdose. Further research is needed to confirm the findings and analyze contributing risk factors for opioid overdoses in a large commercially insured population. OBJECTIVES: To estimate the risk of opioid overdose associated with opioid users exposed to various combinations of opioid, benzodiazepine, and non-benzodiazepine sedative-hypnotic therapy. To identify other factors that are associated with increased risk for opioid overdose. DESIGN: Retrospective cohort study. PATIENTS: New start adult users of opioids, defined as naïve to opioids for 6 months, in Kaiser Permanente California regions from January 2013 through September 2017. MAIN MEASURES: Inpatient or emergency department admissions due to opioid-related overdose. KEY RESULTS: A total of 2,241,530 patients were included in this study. Patients exposed to opioids, benzodiazepines, and non-benzodiazepine sedative-hypnotics at any point during their follow-up were 60% more likely to overdose than those who were only exposed to opioids (p < 0.0001). Those exposed to opioids and benzodiazepines were 20% more likely to have an opioid-related overdose than those exposed to opioids only (p < 0.0001). Significant risk factors for opioid overdose included exposure to all three medication classes, higher opioid dosage strengths, elderly age (age ≥ 65 years), history of previous overdose, and substance use disorder. CONCLUSIONS: Results from this study demonstrate a significant increase in risk of opioid overdose in patients exposed to combinations of sedative-hypnotics with opioids compared to those only taking opioids. Findings from this study provide evidence that opioids should be avoided in combination with benzodiazepines and non-benzodiazepine sedative-hypnotics, used at the lowest dose possible, and used with caution in the elderly, those with previous history of overdose, and those with substance use disorder at baseline.

Risk of injury associated with skeletal muscle relaxant use in older adults.

BACKGROUND: The use of skeletal muscle relaxants (SMRs) among older adults is associated with sedation and confusion, which may lead to an increased risk of falls and injuries. SMRs continue to be used among older adults, although they are on the Beers list as drugs to avoid in the elderly. OBJECTIVE: To investigate the relationship between SMR use and subsequent risk of injury. METHODS: This was a retrospective case-control study of members aged 65 years or older enrolled in an integrated health care system. Cases were defined as patients with a documented injury resulting in either a hospitalization or an emergency department or urgent care visit from January 2009 through December 2010. Cases were matched to controls in a 1:4 ratio by age and sex. Patients had to be enrolled and alive on the date of an injury (index date). SMR exposure for all cases and controls was evaluated within 60 days prior to the index date. Conditional logistic regression adjusted for covariates was performed, with risk estimates presented as odds ratios with 95% confidence intervals. RESULTS: From a base population of 322,806 older adults, we identified 27,974 cases of injury and 104,303 matched controls. Among the cases, 365 (1.30%) used an SMR; among the controls, 801 (0.77%) used an SMR in the 60 days prior to the index date. After adjustment for demographic and clinical covariates, risk of injury was significantly increased for patients using an SMR compared to no use (OR 1.32, 95% CI 1.16-1.50; p < 0.001). Carisoprodol was associated with an increased risk of injury (OR 1.73, 95% CI 1.04-2.88; p = 0.036), as were methocarbamol (OR 1.42, 95% CI 1.16-1.75; p = 0.001) and cyclobenzaprine (OR 1.22, 95% CI 1.02-1.45; p = 0.029). CONCLUSIONS: Older adults using SMRs have an increased risk of injury. These findings provide evidence to support current recommendations to avoid the use of SMRs in elderly patients.

Risk of skeletal-related events in patients with advanced prostate cancer treated with pamidronate or zoledronic acid.

BACKGROUND: Pamidronate and zoledronic acid are used for the prevention of skeletal-related events (SREs) in patients with advanced solid tumors, particularly breast and prostate cancers. There have been no head-to-head clinical trials comparing pamidronate and zoledronic acid among patients with advanced prostate cancer. OBJECTIVE: To estimate the risk of developing an SRE among men with metastatic prostate cancer after being treated with either pamidronate or zoledronic acid. METHODS: A retrospective cohort study was conducted, using data from Kaiser Permanente's Southern California Region. The cohort included men aged > or = 18 years diagnosed with prostate cancer from 1998 to 2004 who received at least 1 infusion of either pamidronate or zoledronic acid after their cancer diagnosis. Patients receiving both drugs and those with a documented SRE prior to diagnosis were excluded. The primary outcome of SREs was defined using diagnosis codes for fractures, spinal cord compression, radiation to bone, and hypercalcemia of malignancy. Secondary outcomes were deterioration in renal function, based on serum creatinine laboratory results, and mortality. Multivariate logistic regression was used to predict SREs and mortality risk for pamidronate compared to zoledronic acid. The proportion of patients with renal function deterioration was analyzed using chi(2) tests. RESULTS: The cohort included 118 patients treated with pamidronate and 274 treated with zoledronic acid. Results showed no significant difference in risk of SREs for pamidronate versus zoledronic acid (OR 0.99; 95% CI 0.59 to 1.67; p = 0.98). No significant difference was found in renal function deterioration (chi(2) 2.08; p = 0.15) or mortality (OR 0.71; 95% CI 0.43 to 1.17; p = 0.18). CONCLUSIONS: For patients with prostate cancer, the choice between these 2 bisphosphonates must be balanced between the shorter infusion time of zoledronic acid versus its increased costs. We found no evidence for a difference in outcomes; therefore, pamidronate is an effective choice where clinic capacity permits.

Evaluation of a Pharmacist-Managed Diabetes Program in a Primary Care Setting Within an Integrated Health Care System.

BACKGROUND: Pharmacists have important roles in managing the therapy of patients with type 2 diabetes and improving patient care. Pharmacists titrate medications; reinforce patient education; and address care gaps, such as medication adherence, vaccinations, and overdue health screenings. Through these efforts and more, pharmacists help to improve patient care and achieve Healthcare Effectiveness Data and Information Set (HEDIS) measures. Thus, it is important to demonstrate improved health outcomes through pharmacist contributions to diabetes management, which can then provide an opportunity to expand the role of clinical pharmacists in other medical centers and practice settings within an integrated health care system. OBJECTIVE: To evaluate the effect of a pharmacist-managed program within a primary care setting by determining the percentage of patients who reached the HEDIS goal of hemoglobin A1c (A1c) < 8.0%, the time needed to reach this goal, and A1c reduction in patients with type 2 diabetes. METHODS: This retrospective cohort study identified patients aged 18-74 years who had uncontrolled A1c ≥ 8.0%. Patients in the Complete Care Program (CCP) had their diabetes therapy managed by a pharmacist and were propensity score matched to a comparison group of usual care (UC) patients. Multivariate regression analyses and a Cox proportional hazards model compared the change in A1c from baseline and the time to A1c goal between the 2 groups. RESULTS: There were no significant differences in baseline characteristics between the CCP and UC patients (n = 980 patients per group). CCP patients were significantly more likely to achieve the HEDIS goal of A1c < 8% at 3 months (OR = 2.44, 95% CI = 1.93-3.10, P < 0.0001) and at 6 months (OR = 1.32, 95% CI = 1.08-1.61, P = 0.007) compared with the UC patients. CCP patients also reached the A1c goal significantly faster: 3.4 months versus 4.6 months (P < 0.0001), even after controlling for covariates (HR = 1.24, 95% CI = 1.09-1.41, P = 0.001). Change in baseline A1c was -0.95% versus -0.54% (P < 0.0001) at 3 months and -1.19% versus -0.99% (P = 0.008) at 6 months for CCP versus UC patients, respectively. CONCLUSIONS: Type 2 diabetes therapy management by clinical pharmacists was associated with a greater percentage of patients achieving the HEDIS goal of A1c < 8.0%, reaching the A1c goal faster, and a greater A1c reduction from baseline at 3 and 6 months of follow-up compared with patients receiving usual care. DISCLOSURES: No funding was provided to support this research study. The authors report no potential conflicts of interest relevant to this article. All authors contributed to the study concept and design. Benedict and Spence performed data analysis and interpretation. The manuscript was written by Benedict, with assistance from Spence and Rashid. All authors reviewed and contributed to manuscript revisions. Spence is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Parts of this study were presented at the AMCP Managed Care and Specialty Pharmacy Annual Meeting; San Francisco, California; April 19-22, 2016.

Effects on resource utilization of adding salmeterol in combination or separately to inhaled corticosteroids.

BACKGROUND: The addition of a long-acting beta-agonist (LABA) to an inhaled corticosteroid (ICS) for patients with moderate or severe persistent asthma improves outcomes such as pulmonary function, reduces exacerbations requiring oral steroids, and reduces use of rescue beta-agonists. OBJECTIVE: To assess the key resource utilization outcomes of adding salmeterol, a LABA, to fluticasone, an ICS, either as a fixed-combination inhaler (fluticasone-salmeterol [FSA] or as a separate inhaler used concomitantly with the ICS beclomethasone (BSA). METHODS: This is a retrospective, observational database study that extracted data from electronic medical and prescription records in which the prescription written was identical to the prescription dispensed. The sample included asthmatic patients aged 12 to 55 years who received a medium dose of an ICS (240-480 mcg of beclomethasone, 264-660 mcg of fluticasone, 600-1,200 mcg of budesonide, or 1,000-2,000 mcg of triamcinolone acetonide) between July 2001 and December 2002 and had salmeterol added to the regimen (index date). From this population of patients, the analytical cohort was derived to include 1,213 patients who received FSA and a matched cohort of 1,213 patients who received BSA. The primary endpoint was an asthma-related event (ARE), which was defined as (1) an emergency department (ED) visit or (2) hospital admission with a primary asthma diagnosis code (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 493.xx). The secondary endpoints were the (1) use of short-acting beta-agonist (SABA) equivalents, (2) percentage of patients who received 1 or more oral steroid prescriptions, (3) patterns of ICS use, and (4) refill rates of salmeterol. All data were collected for 6 months before and 6 months after the index date, defined as the first prescription dispensed to the patient that included salmeterol as an ingredient. RESULTS: Outcomes were improved in both cohorts with no significant difference in the likelihood of an ARE, 60 patients (4.9%) for FSA and 90 patients (8.1%) for BSA (odds ratio [OR], 0.668; 95% confidence interval [CI], 0.443-1.008); P=0.055). FSA was associated with a reduction in AREs of 55% (10.9%-4.9%; P <0.001), and BSA with a reduction in AREs of 39% (13.3%-8.1%; P <0.001). FSA compared with BSA was associated with a greater reduction in SABA use (-0.66 canister equivalents over 6 months, P <0.001) and a lower likelihood of filling an oral steroid prescription, 35.8% of FSA patients compared with 38.0% of BSA patients (OR, 0.801; 95% CI, 0.662-0.970; P=0.023). For the 132 FSA patients (10.9%) and 162 BSA patients (13.4%) who had an ARE in the preperiod, those who received FSA in the postperiod had a 47% lower likelihood of a subsequent ARE, 17.4% of 132 patients compared with 27.8% of 162 BSA patients (OR, 0.527; 95% CI, 0.291-0.954; P=0.034). No ARE differences in subgroup analyses were noted for patients without an ARE in the preperiod or for patients using more than 6 canisters of SABA. More patients in the FSA group took daily doses of 400 mcg or more of ICS than those in the BSA group (32.0% compared with 10.0%, P <0.001). The average refill rate for salmeterol was 2.71 prescriptions (SD=1.42) over 6 months for FSA compared with 2.38 (SD=1.49) for BSA (P <0.001). CONCLUSION: Overall, the addition of salmeterol as a fixed combination with fluticasone or with beclomethasone as separate inhalers was associated with a reduction in the ARE rate. Patients who received FSA were more likely to be exposed to a higher dose of ICS compared with those who received BSA. Differences in resource utilization may be attributed to how these drugs are prescribed and taken by patients in a real-practice (naturalistic) setting rather than to any inherent difference between the drugs (i.e., higher ICS dose rather than greater efficacy).

Longitudinal study of new and prevalent use of self-monitoring of blood glucose.

OBJECTIVE: We sought to assess longitudinal association between self-monitoring of blood glucose (SMBG) and glycemic control in diabetic patients from an integrated health plan (Kaiser Permanente Northern California). RESEARCH DESIGN AND METHODS: Longitudinal analyses of glycemic control among 1) 16,091 patients initiating SMBG (new-user cohort) and 2) 15,347 ongoing users of SMBG (prevalent-user cohort). SMBG frequency was based on pharmacy use (number of blood glucose test strips dispensed), and glycemic control was based on HbA(1c) (A1C). In the new-user cohort, ANCOVA models (pre- and posttest design) were used to assess the effect of initiating SMBG. In the prevalent-user cohort, repeated-measure, mixed-effects models with random-intercept and time-dependent covariates were used to assess changes in SMBG and A1C. All models were stratified by therapy (no medications, oral agents only, or insulin) and adjusted for baseline A1C, sociodemographics, insulin injection frequency, comorbidity index, medication adherence, smoking status, health care use, and provider specialty. RESULTS: Greater SMBG practice frequency among new users was associated with a graded decrease in A1C (relative to nonusers) regardless of diabetes therapy (P < 0.0001). Changes in SMBG frequency among prevalent users were associated with an inverse graded change in A1C only among pharmacologically treated patients (P < 0.0001). CONCLUSIONS: These observational findings are consistent with short-term benefits of initiating SMBG practice for all patients but continuing benefits only for pharmacologically treated patients. Differences in effectiveness between new versus prevalent users of SMBG have implications for guideline development and interpretation of observational outcomes data.

Treatment Patterns and Overall Survival Associated with First-Line Systemic Therapy for Patients with Advanced Non-Small Cell Lung Cancer.

BACKGROUND: A variety of regimens are used as first-line treatment in patients with advanced non-small cell lung cancer (NSCLC), which may include combination regimens and single agents, depending on histology, molecular profile, and performance status. OBJECTIVE: To describe the types of first-line therapies and compare overall survival between therapies used for patients with advanced NSCLC in an integrated health care system. METHODS: This retrospective cohort study included patients aged 18 years or older from Kaiser Permanente California with a diagnosis of stage IIIB/IV NSCLC. First systemic treatment date occurred from January 1, 2008, through September 30, 2013. Overall survival was measured as the number of months from initial treatment until death, end of enrollment, or September 30, 2014. Treatment regimens were categorized into 6 mutually exclusive groups: platinum doublets; pemetrexed-based, bevacizumab-based, and pemetrexed + bevacizumab-based combinations; singlets; and tyrosine-kinase inhibitors (TKIs). Survival was compared using Kaplan-Meier curves and adjusted Cox proportional hazard models. Subgroup analyses were performed by age group and by nonsquamous histology. RESULTS: Of 2,081 patients, approximately half (52.3%) received platinum doublets, followed by TKIs (19.0%), pemetrexed-based regimens (13.4%), bevacizumab-regimens (8.0%), singlets (5.5%), and pemetrexed + bevacizumab-based combinations (1.8%). Median survival was longest for pemetrexed + bevacizumab-based combinations (18.5 months), followed by bevacizumab-based regimens (14.5), TKIs (12.7), pemetrexed-based regimens (10.4), doublets (9.2), and singlets (5.3). There was a significantly reduced risk of mortality for pemetrexed + bevacizumab-based combinations (HR = 0.64; 95% CI = 0.42-0.94) and TKIs (HR = 0.83; 95% CI = 0.73-0.94) compared with doublets. Singlets were associated with an increased risk of mortality (HR = 1.50; 95% CI = 1.22-1.84). Subgroup analysis among patients aged 65 years and over found no significant differences among treatment groups, with the exception of singlets, which were associated with an increased risk of mortality compared with doublets (HR = 1.51; 95% CI = 1.20-1.90). Among patients under aged 65 years, pemetrexed + bevacizumab-based combinations (HR = 0.36; 95% CI = 0.21-0.64) and TKIs (HR = 0.76; 95% CI = 0.59-0.97) were associated with a reduced risk of mortality, and singlets were associated with an increased risk (HR = 1.85; 95% CI = 1.17-2.92). CONCLUSIONS: In this cohort of patients with advanced NSCLC, patients received a platinum agent with or without bevacizumab or pemetrexed, a TKI, or a single agent. Younger patients (aged < 65 years) receiving bevacizumab + pemetrexed-based combinations had a survival advantage over those receiving platinum doublets, and this finding merits further investigation. Younger patients receiving TKIs also had longer survival. Compared with platinum doublets, we found no survival advantage for older patients receiving bevacizumab or pemetrexed, which suggests that combination therapy of a platinum agent and taxane, such as carboplatin and paclitaxel, could be a reasonable option for older patients who are not candidates for targeted therapy. DISCLOSURES: No outside funding supported this study. Rashid has received past funding from Bristol-Myers Squibb, Astellas, Novartis, and Pfizer. No other authors report any potential financial conflicts of interest. Study concept and design were primarily contributed by Spence and Hui, with input from the other authors. Hui, Spence, and Rashid took the lead in data collection, and data interpretation was performed by Schottinger, Millares, and Spence, assisted by the other authors. The manuscript was written primarily by Spence, along with Chang, and revised by Spence, with input from the other authors.

Cost reduction strategies used by elderly patients with chronic obstructive pulmonary disease to cope with a generic-only pharmacy benefit.

BACKGROUND: Generic-only pharmacy benefits may present more of a burden to patients with chronic disease conditions such as chronic obstructive pulmonary disease (COPD), where generic drug therapy choices are more limited. OBJECTIVE: To evaluate the strategies that elderly patients with COPD use to manage their out-of-pocket (OOP) prescription expenses in a generic-only pharmacy benefit compared with similar patients with a single-tier copayment or a 2-tier pharmacy benefit with coverage of brand formulary drugs. METHODS: Surveys were mailed to a sample of 3,000 Kaiser Permanente (California) patients (aged > or = 65 years) who had a diagnosis for COPD and received at least 1 prescription for a COPD-related medication during 2003. The sample was stratified by type of pharmacy benefit: generic-only, single copayment tier, and 2 copayment tiers. The survey contained questions about strategies used to reduce OOP prescription expenses, such as stop taking a prescribed medication, purchase prescriptions out of the country, or discuss OOP prescription expenses with a physician. The likelihood of using specific strategies to reduce OOP prescription expenses was modeled using logistic regression. Covariates included social support, quality of life, smoking status, socioeconomic status, total prescription costs, and demographics. RESULTS: A total of 1,624 surveys were returned, for a 54% response rate. Results from logistic regressions indicate that COPD patients with a generic-only benefit are significantly more likely to report that they discussed their OOP costs with their physician (odds ratio [OR]=9.02; 95% confidence interval [CI], 6.15- 13.22), purchased their medications from another country (OR=6.70; 95% CI, 3.17-14.16) and reduced spending on food and clothing (OR=4.06; 95% CI, 2.70-6.12). They are also more likely to report that they had taken less than the prescribed amount of a regular medication (OR=1.70; 95% CI, 1.25-2.31) and that they stopped taking one or more of their regular medications (OR=1.77; CI, 1.27-2.47). Patients with low annual household incomes (<25,000 US dollars) were significantly more likely to discuss their OOP costs with their physician (OR=1.47; 95% CI, 1.08-2.00 ) and to reduce spending on food and clothing (OR=1.97; 95% CI, 1.42-2.73) than those with higher incomes. Approximately 15% of COPD patients obtained drug samples from their physicians as a method to reduce OOP costs, and there was no difference among the 3 groups in the prevalence of this cost management strategy. Overall, patients in the generic-only pharmacy benefit used an average of 3 methods to reduce OOP pharmacy costs compared with approximately 1.5 cost reduction methods used by patients in single-tier and 2-tier copayment designs who had coverage of formulary brand as well as generic drugs. CONCLUSION: Elderly patients with COPD and a generic-drug-only pharmacy benefit are more likely to report using a variety of strategies to reduce their OOP costs compared with similar patients with single-tier copayment or 2-tier copayment pharmacy benefits. The most common strategy was discussing OOP costs with their physician, and use of this strategy was inversely related to household income. There was no difference in the proportion of COPD patients among the 3 pharmacy benefit groups that used drug samples from their physicians as a means to reduce OOP costs.

The Risk of Pneumonia in Older Adults Using Nonbenzodiazepine Hypnotics.

BACKGROUND: Previous studies have shown an increased risk of pneumonia with benzodiazepines (BZD) and an increased risk of any infection with non-BZD hypnotics, but no analysis has specifically investigated the risk of pneumonia with non-BZD hypnotic use. OBJECTIVE: To evaluate the risk of pneumonia associated with non-BZD hypnotic use in the elderly. METHODS: This was a retrospective case-control study of members aged 65 years and older enrolled in an integrated health care system. Cases were identified as patients aged 65 years and older with a diagnosis of pneumonia from January 2011 to December 2012. Controls were matched in a 4:1 ratio to cases based on age, gender, and active enrollment. Non-BZD hypnotic exposure was evaluated for all cases and controls 1 year before the index date. Proximity of exposure to index date and duration of use were analyzed. Conditional logistic regression adjusted for covariates was performed. RESULTS: We identified 51,029 cases with pneumonia and matched 188,391 controls without pneumonia. Of the cases with pneumonia, 5.5% (2,790) of cases had exposure to a non-BZD hypnotic, compared with 3.4% (6,345) of controls. Non-BZD hypnotic exposure was associated with an increased risk of pneumonia (OR = 1.14; 95% CI = 1.08-1.20). When exposure was stratified by proximity to index date, only current exposure was associated with an increased risk of pneumonia (OR = 1.27; 95% CI = 1.18-1.36). Short-term exposure was associated with a relatively higher risk of pneumonia (OR = 1.57; 95% CI = 1.39-1.77) compared with long-term use (OR = 1.16; 95% CI = 1.06-1.25). CONCLUSIONS: Current use of non-BZD hypnotics in older adults is associated with an increased risk of pneumonia. The findings of this study provide additional support for reducing the use of non-BZD hypnotics in older adults and for pursuing safer alternatives for treating insomnia. DISCLOSURES: No outside funding supported this study. At the time of this study, Jung was a PGY2 resident in drug information at Kaiser Permanente Drug Information Services. All authors are employed by Kaiser Permanente and report no other potential financial conflicts of interest. Study concept and design were contributed by Jung, Spence, Lee, and Gibbs. Jung, Spence, and Hui were responsible for data collection, and data interpretation was performed by Jung and Spence, with assistance from Escasa, Lee, and Hui. The manuscript was primarily written by Jung, along with Spence and Escasa, and revised by Spence, Escasa, and Lee, along with the other authors.

Identifying Subsequent Therapies in Patients with Advanced Non-Small Cell Lung Cancer and Factors Associated with Overall Survival.

STUDY OBJECTIVES: To identify subsequent therapies used after first-line therapies in patients with advanced non-small cell lung cancer (NSCLC), compare overall survival (OS) associated with subsequent therapies, and evaluate factors associated with OS in these patients. METHODS: The study was a retrospective cohort analysis of patients with advanced NSCLC (stage IIIB/IV) who were initiated on first-line therapy from January 1, 2008, through September 30, 2013, and afterward given subsequent chemotherapy (index date). Patients had to be 18 years or older at the time of diagnosis of advanced NSCLC. Patients were followed from the index date until one of the following end points: end of the study (September 30, 2014), disenrollment from the health plan, or death-whichever came the earliest. The primary outcome was OS. Kaplan-Meier curves and Cox proportional hazard models were used to analyze OS and evaluate the factors associated with OS. RESULTS: The analysis included 1280 patients on subsequent therapies. The most common subsequent therapies were pemetrexed (284 patients [22%]), erlotinib (216 patients [17%]), and docetaxel (139 patients [11%]). Patients from the singlets group had a lower OS at 6.3 months compared with all other groups: pemetrexed based, combination of pemetrexed and bevacizumab based, bevacizumab based, doublets, and tyrosine kinase inhibitors (p<0.0001). Factors associated with greater OS included age younger than 65 years, female gender, and a longer time between initiation of first and subsequent therapies. Factors associated with a reduction in OS were pemetrexed-based or singlet regimens for subsequent therapy, diagnosis of squamous histology, and a higher number of adverse events prior to subsequent therapy. CONCLUSION: We found that a subsequent therapy consisting of singlets is associated with reduced OS compared with other chemotherapy groups. Patient characteristics such as female gender, age younger than 65 years, diagnosis of nonsquamous histology, and/or a longer time frame between initiation of first-line and subsequent chemotherapy are associated with longer survival.

Direct-to-consumer advertising of COX-2 inhibitors: effect on appropriateness of prescribing.

Spending on direct-to-consumer advertising (DTCA) of prescription drugs has increased dramatically in the past several years. An unresolved question is whether such advertising leads to inappropriate prescribing. In this study, the authors use survey and administrative data to determine the association of DTCA with the appropriate prescribing of cyclooxygenase-2 (COX-2) inhibitors for 1,382 patients. Treatment with either a COX-2 or a traditional nonsteroidal anti-inflammatory drug (NSAID) was defined as appropriate or not according to three different definitions of gastrointestinal risk. Patients who saw or heard a COX-2 advertisement and asked their physician about the advertised drug were significantly more likely to be prescribed a COX-2 (versus a NSAID, as recommended by evidence-based guidelines) than all other patients. Findings also suggest that some patients may benefit from DTCA. The authors discuss the need for balanced drug information for consumers, increased physician vigilance in prescribing appropriately, and further study of DTCA.

Risk of Injury in Older Adults Using Gastrointestinal Antispasmodic and Anticholinergic Medications.

OBJECTIVES: To determine the risk of injury associated with gastrointestinal (GI) antispasmodic and anticholinergic use in elderly adults. DESIGN: Retrospective case-control study. SETTING: Integrated healthcare system. PARTICIPANTS: Healthcare system members aged 65 and older (N = 260,010; 54,152 cases, 205,858 controls). MEASUREMENTS: Cases were identified as individuals with an injury resulting in a hospitalization, emergency department, or urgent care visit (index date) from January 2009 through December 2010. Cases and controls were matched in a 1:4 ratio based on age and sex. GI antispasmodic and anticholinergic current and past exposure for cases and controls was evaluated. Individuals were classified as current users if the days' supply of the GI prescription overlapped the index date and past users if the days' supply ended more than 60 days before the index date. Duration of use for current users was analyzed for short- and long-term use. Conditional logistic regression produced adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Of the total population, 1,068 (0.4%) had current exposure to a GI antispasmodic or anticholinergic (302 (0.6%) cases, 766 (0.4%) controls). Current users had a small but significantly greater risk of injury than nonusers (OR = 1.16, 95% CI = 1.01-1.34, P = .03). Past use was not significantly different from no use. Short-term users had a significantly greater risk of injury (OR = 1.31, 95% CI = 1.01-1.70, P = .04) than nonusers. Long-term use was associated with greater risk, but the difference was not statistically significant. CONCLUSION: Older adults using GI antispasmodic and anticholinergic drugs have greater risk of injury. These findings support recommendations to limit the prescribing of GI antispasmodics and anticholinergics in elderly adults.

Impact of a Medicare MTM program: evaluating clinical and economic outcomes.

OBJECTIVES: To assess the impact of a Medicare Medication Therapy Management (MTM) program in a large integrated health plan on patient mortality, hospitalization and emergency department (ED) utilization, and daily prescription costs. STUDY DESIGN: Retrospective matched cohort study. METHODS: Patients who received MTM services between 2006 and 2010 were matched to control patients who were enrolled in Medicare but did not receive MTM services. They were matched in a 1:4 ratio based on age, gender, geographic location, and prospective diagnostic-cost-group (DxCG) risk score. Multivariate regressions were used to analyze the outcomes. Subgroup analyses were conducted for patients enrolled in 2010 because the Centers for Medicare & Medicaid Services lowered the drug-cost threshold for MTM eligibility and changed from opt-in to optout participation. RESULTS: We identified 34,532 members who received MTM services and 138,128 control members. The MTM group was found to have a significantly reduced mortality (hazard ratio 0.86, 95% confidence interval [CI], 0.84-0.88; P <.001), lower odds for hospitalization (odds ratio [OR] = 0.97, 95% CI, 0.94-0.99; P = .018), higher odds for emergency department visits (OR = 1.17, 95% CI, 1.14-1.20; P <.001), and no differences in change in daily medication costs when compared to the matched group. The subgroup analysis of the 2010 cohort found similar results with better outcomes than the overall cohort. CONCLUSIONS: Medicare MTM services resulted in lower mortality and odds for hospitalization for enrolled patients compared with matched controls. This study observed an increase in ED visits and no differences in change in daily medication costs in MTM services.

Evaluation of an outpatient pharmacy clinical services program on adherence and clinical outcomes among patients with diabetes and/or coronary artery disease.

BACKGROUND: Poor medication adherence among patients with chronic diseases can result in complications and increased health care expenditures. An outpatient pharmacy clinical service (OPCS) program targeted nonadherent diabetes mellitus (DM) and/or coronary artery disease (CAD) patients with hemoglobin A1c (HbA1c) and/or low-density lipoprotein cholesterol (LDL-C) outside clinical goals. Pharmacists engaged identified patients with a face-to-face B-SMART consult, a consultation methodology to identify Barriers to medication adherence, work on Solutions to identified barriers, Motivate patients, recommend Adherence tools, reinforce the pharmacist-patient Relationship, and Triage if needed, to other services such as health education to improve outcomes.  OBJECTIVES: To (a) assess rates of medication adherence and clinical outcomes in the OPCS program compared with usual care in an integrated health care system and (b) estimate return-on-investment (ROI) from this intervention.  METHODS: This retrospective cohort study used data from the Kaiser Permanente Southern California region to identify patients who received OPCS consultations and usual care patients from March 2009 through December 2010, with 1 year of follow-up from the initial consult (index date). Four patients from usual care were matched to each patient in the OPCS program and were assigned the same index date as the matching OPCS patient. Additional selection criteria were applied after matching. All patients were required to have a medication possession ratio (MPR) of less than 0.80 for their diabetes or dyslipidemia oral medications 1 year prior to the index date, indicating lower adherence to the prescribed therapy. Diabetic patients or dyslipidemic patients had to have a HbA1c or LDL-C lab result outside of clinical goals prior to the index date to be included in the study, respectively. Adherence outcomes as well as clinical outcomes were measured 12 months after the index date using chi-square tests for differences in percentages and t-tests for differences in means. The ROI was based on a cost-avoidance model that compared the cost of the OPCS program with the cost savings gained through reduced hospitalizations and emergency department (ED) visits. The diabetes and dyslipidemia cohorts were combined for the ROI analysis. RESULTS: Demographic and clinical characteristics at baseline were similar between the OPCS group (n = 1,480) and usual care group (n = 1,477). Among patients with diabetes, a higher percentage in the OPCS group than in the usual care group were adherent with their diabetes medications (53.5% vs. 37.4%, P = 0.001). There was no significant difference in average MPR between groups. However, patients in the OPCS group had a greater increase in mean MPR (0.19 vs. 0.15, P = 0.024); were less likely to discontinue taking their diabetes medications (11.7% vs. 35.5%, P = 0.001); and were more likely to have a timely first fill after the index date (34.8% vs. 12.9%, P = 0.001). The average number of days to the first fill after the index date was significantly shorter for the OPCS group (79.3 vs. 156.3, P = 0.001). Regarding clinical outcomes, patients with diabetes in the OPCS group had a lower mean HbA1c (8.48 vs. 8.80, P = 0.024) and a greater reduction in HbA1c (-1.25 vs. -0.75, P = 0.001) than in the usual care group. They were also less likely to have an ED visit (1.67% vs. 4.21%, P = 0.040), but there was no significant difference in the percentage of patients with a hospital admission. Among patients with dyslipidemia, the mean MPR was significantly lower for the OPCS group than the usual care group (0.70 vs. 0.74, P = 0.003). There were no significant differences in the percentage of adherent patients or the change in mean MPR from baseline. However, the OPCS group was significantly less likely to discontinue dyslipidemia medications (21.1% vs. 35.4%, P less than 0.001) and more likely to have a timely fill (28.3% vs. 15.1%, P less than 0.001). The average days to first fill after the index date was 106.9 for the OPCS group, compared with 162.6 for the usual care group (P less than 0.001). The OPCS group had a lower mean LDL-C (105.1 vs. 110.4, P = 0.001) and a greater reduction in LDL-C (-30.5 vs. -22.4, P = 0.001) than the usual care group. There were no significant differences in the percentage of patients with an ED visit or a hospital admission. In terms of ROI, assuming that 58% of hospitalizations and 8.5% of ED visits incurred in the usual care group were avoidable, approximately $5.79 could be saved for every dollar spent on the OPCS program.  CONCLUSION: By engaging nonadherent patients to restart their DM or lipid medications during a face-to-face consult, the OPCS pharmacist was able to influence and improve medication adherence and clinical outcomes, particularly among patients with diabetes. A positive ROI was demonstrated.

Evaluation of clinical and safety outcomes associated with conversion from brand-name to generic tacrolimus in transplant recipients enrolled in an integrated health care system.

STUDY OBJECTIVE: To evaluate clinical and safety outcomes among transplant recipients whose tacrolimus was converted from the brand-name formulation to a generic formulation. DESIGN: Retrospective analysis. DATA SOURCE: Clinical databases and electronic records from a large, integrated health care system in California. PATIENTS: A total of 234 clinically stable, adult transplant recipients (renal, liver, and heart) whose tacrolimus was converted from the brand-name formulation to a generic formulation between October 1, 2010, and December 31, 2010, according to a physician-approved protocol. MEASUREMENTS AND MAIN RESULTS: For each patient, pre- and postconversion tacrolimus trough concentrations and serum creatinine concentrations were analyzed. Data were also collected on the percentage of patients who required dosage titration, drug cost savings, and rates of reversion to brand-name tacrolimus, biopsy-proved acute allograft rejections, and mortality. No significant differences were noted in mean ± SD pre- and postconversion tacrolimus trough levels (6.74 ± 1.61 vs 6.96 ± 2.31 ng/ml, p=0.137) or serum creatinine concentrations (1.33 ± 0.48 vs 1.36 ± 0.82 mg/dl, p=0.302). The mean ± SD percent change in tacrolimus trough concentration was 5.63 ± 32.95%. Thirty-six patients (15.4%) required dosage titration. Six patients (2.6%) reverted back to brand-name tacrolimus. No deaths or acute rejections occurred. Use of the generic product saved each patient an average of $45/month in drug acquisition cost and $26/prescription copayment. CONCLUSION: Clinical experience as well as research data show that use of generic tacrolimus results in trough concentrations that are comparable to the brand-name drug. Given the lack of adverse events reported and the cost savings recognized, conversion from brand-name tacrolimus to generic tacrolimus should be encouraged. Since dosage titration may be required, close therapeutic drug monitoring is recommended.

Evaluation of a pharmacist-managed amiodarone monitoring program.

BACKGROUND: Because of the potential for serious adverse effects, patients treated with amiodarone must be carefully screened and routinely monitored for potential liver, thyroid, and pulmonary toxicity. However, laboratory and pulmonary monitoring rates have been found to be substantially lower than recommended in guidelines, including those of the North American Society of Pacing and Electrophysiology (NASPE, 2007). OBJECTIVE: To (a) assess rates of laboratory monitoring of liver, thyroid, and pulmonary function and adverse events in a pharmacist-managed amiodarone monitoring program compared with usual care in an integrated health care system and (b) estimate return on investment (ROI) from this intervention. METHODS: This retrospective cohort study used clinic and enrollment data to identify those patients in the pharmacist-managed program and usual care who received at least 100 days of amiodarone therapy with the first prescription for amiodarone (index) from June 1, 2007, through May 31, 2009 (index date). Laboratory test monitoring was recorded at baseline (up to 6 months before the index date), from 1-6 months after the index date, 7-12 months after the index date, and at any time during the year (months 1-12). Alanine aminotransferase (ALT) was evaluated for liver function. Thyroid-stimulating hormone (TSH) and, for patients with abnormal TSH ( less than 0.4 micro international units [uIU] per mL or greater than 4.0 uIU per mL), free thyroxine (T4) were evaluated for thyroid function. Rates of pulmonary function testing (PFT) were measured by the diffusion capacity of carbon monoxide tests (DLCO) and annual chest x-rays (CXR); electrocardiograms were not counted. Monitoring rates were compared using Pearson chi-square tests, and logistic regression was used to compare the odds of testing (ALT, TSH, T4, CXR, PFT) between the 2 groups at any time during the year after the index date. Concomitant uses of amiodarone with high-dose statins and of amiodarone with digoxin were compared using Pearson chi-square tests. Hospitalizations and emergency room (ER) visits during the 12-month follow-up period were counted for (a) interstitial lung disease; (b) rhabdomyolysis for patients who received amiodarone with high-dose statins (either lovastatin greater than 40 mg per day or greater than 20 mg per day of simvastatin or atorvastatin); and (c) for patients with abnormal digoxin, ALT, TSH, or T4 levels, if the hospitalization occurred within 2 days of the abnormal laboratory value. RESULTS: There were 2,292 patients who received at least 100 days of amiodarone therapy and met the other inclusion criteria, of whom 181 patients (7.9%) were in the pharmacist-managed group and 2,111 received usual care. There were 90 (49.7%) new amiodarone users in the pharmacist-managed group and 990 (46.9%) in usual care. The 2 groups had similar demographic characteristics except race, with more whites and fewer African Americans, Asians, and Hispanics in usual care. Laboratory monitoring rates for ALT, TSH, and T4 were significantly higher in the pharmacist-managed group than usual care at the first and second 6 months and at baseline for ALT and TSH but not T4. Baseline CXR rates were significantly higher for the pharmacist-managed group than usual care (59.1% vs. 49.3%; P=0.011). Few patients in either group received PFT tests at baseline, 6.6% versus 3.6% (P=0.042). After controlling for covariates (age, gender, race, new vs. continuing use, and comorbidities), pharmacist-managed patients were significantly more likely to have at least 1 ALT test within the year after the index prescription (odds ratio [OR]=3.13, 95% CI=1.12-8.71), as well as a TSH test (OR=8.13, 95% CI=3.27-20.21) and T4 (OR=2.51, 95% CI=1.67-3.75). PFTs were also more likely to be given to these patients (OR=5.89, 95% CI=3.86-8.99). A higher percentage of patients in the pharmacist-managed group than in usual care were taking a high-dose statin during the 12-month follow-up period (47.5% vs. 36.2%, P=0.003), but of those patients, a greater proportion were switched to another statin (14.0% [n=12] vs. 7.5% [n=57], P=0.037) or a lower dose (9.3% [n=8] vs. 3.9% [n=30], P=0.022). Six patients in the usual care group (0.79% of patients on high-dose statins) developed rhabdomyolysis, and 5 (0.24% of all patients in usual care) had an admission for interstitial lung disease. The proportions of patients using amiodarone and digoxin concomitantly were similar in the 2 groups (35.9% vs. 31.3%, P=0.197). Among patients with abnormal laboratory results for ALT, TSH, and T4, or digoxin, there were 2 all-cause hospitalizations and 1 ER visit in the pharmacist-managed group and 34 all-cause hospitalizations and 18 ER visits in the usual care group during the follow-up year. Assuming that all hospitalizations and ER visits incurred in the usual care group were avoid- able, approximately $2.14 could be saved for every dollar spent on the pharmacist-managed amiodarone monitoring program. CONCLUSIONS: Pharmacist management of patients treated with amiodarone was associated with improved monitoring of recommended laboratory tests and PFTs.

Effect of cost-sharing changes on self-monitoring of blood glucose.

OBJECTIVE: To study the effect of cost-sharing policy changes on utilization of test strips for self-monitoring of blood glucose. STUDY DESIGN: A legislative mandate (January 1, 2000) required California health plans to cover diabetes supplies, including those for self-monitoring of blood glucose. One health plan, Kaiser Permanente Northern California, initially waived established copayments and provided free test strips to members with diabetes mellitus for 2 years but later instituted a 20% coinsurance charge for a portion of their membership. METHODS: A retrospective cohort design was used to study pharmacy-based estimates of test strip utilization changes during this natural experiment. Analyses included 2 cohort investigations using pretest-posttest analysis with control subjects to study transitions from a copayment period to a free test strip period and from the free test strip period to a coinsurance period. RESULTS: During the copayment period, test strip utilization was inversely related to copayments for test strips. Offering free test strips did not increase utilization, even among those paying higher copayments before the policy change. Price-elastic patterns formed before and during the copayment period persisted, despite receiving free test strips for 2 years. The coinsurance, introduced after 2 years of receiving free test strips, resulted in statistically significant (but not clinically relevant) decreased utilization (approximately 1-3 fewer test strips/month). Change patterns did not differ by socioeconomic status. CONCLUSIONS: Offering free test strips shifted costs from patient to health plan, without improving adherence. The introduced coinsurance slightly reduced utilization and adherence to recommendations about self-monitoring of blood glucose. Neither intervention had marked clinical effect. Cross-sectional analyses should not be used to predict utilization changes in the face of rapidly evolving benefit policies.