Effect Of Justicia Adhatoda (Malabar Nut) Leaf Extract On Drug-Induced Coagulopathy In Mice And In-Vitro Platelet Aggregation Of Human Blood.

BACKGROUND: Justicia adhatoda is widely used in traditional medicine for treatment of menorrhagia, piles and bleeding disorders. Oral antiplatelet and anticoagulant drugs are routinely prescribed to patients with cardiovascular diseases. These drugs have one major adverse effect that they can cause spontaneous haemorrhage, which can be fatal. Development of a haemostatic agent can help in effective management of drug-induced haemorrhages. This study was devised to observe the effect of leaf extract of Justicia adhatoda on coagulation profile in mice and to evaluate its effect on in-vitro platelet aggregation. METHODS: The study was divided into two parts. First part was designed to evaluate the effect of J. adhatoda leaf extract on coagulation parameters. Three drugs were used to induce coagulopathy viz., warfarin, aspirin and dabigatran. Bleeding time, platelet count, PT and APTT were estimated. Second part of this study was devised to observe the effect of J. adhatoda leaf extract on in vitro platelet aggregation of human. Percent aggregation was recorded by light transmission aggregometer for three minutes. RESULTS: Leaf extract of Justicia adhatoda decreased bleeding time from 6.1±2.36 minutes in normal control to 1.9±1.03 minutes in extract treated mice. There was no effect on the coagulation parameters. Platelet count increased significantly only in the aspirin treated group that received the extract to 540±46.8x103 /µl from 436.9±37.9x103 /µl of aspirin treated group. Platelet aggregation in vitro increased in a dose dependent manner. CONCLUSION: Justicia adhatoda leaf extract is effective in controlling excessive bleeding in vivo, in mice with acquired platelet defect produced by aspirin. This haemostatic effect is probably due to increased platelet aggregation as indicated by the in vitro results.

Glycemic Control after Initiating Direct-Acting Antiviral Agents in Patients with Hepatitis C Virus and Type 2 Diabetes Mellitus Using the United States Integrated Healthcare System.

OBJECTIVE: Hepatitis C virus (HCV) has an increased risk of Type 2 diabetes mellitus (T2DM). Prior studies found that the eradication of HCV with direct-acting antiviral (DAA) agents led to improved glycemic control in patients with T2DM. We aimed to identify the association between HCV eradication and glycemic control in patients diagnosed with HCV and T2DM. METHODS: A retrospective observational study was conducted to identify adult patients diagnosed with HCV from January 1, 2014, to August 31, 2017. Patients were included if they were initiated on one of the following DAA agents within the study period: Sofosbuvir/velpatasvir, sofosbuvir/ledispavir, elbasvir/grazopevir. Patients were also required to have the diagnosis of T2DM. The primary outcome of this study was the average change in glycosylated hemoglobin (HbA1c) pre- versus post-DAA agents. FINDINGS: Our final cohort consisted of 996 patients diagnosed with HCV and T2DM: Patients who achieved sustained virologic response (SVR) (n = 937, 94%) and those who did not achieve SVR (n = 59, 6%). In the SVR group, there was a 0.3950% reduction in HbA1c (P < 0.0001) and in those who did not achieve SVR group, there was 0.3532% reduction in HbA1c (P = 0.0051). In the overall study population, SVR group had 0.04% more reduction in HbA1c but was not statistically significant (P = 0.7441). CONCLUSION: Both groups had statistically significant reductions in HbA1c when comparing the mean change in average HbA1c pre-versus post-DAA agent. Patients who achieved SVR had a greater absolute reduction in HbA1c by 0.04%; however, this was not statistically significant.

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.

Real world treatment patterns in chronic myeloid leukemia patients newly initiated on tyrosine kinase inhibitors in an U.S. integrated healthcare system.

Purpose To evaluate treatment patterns in patients diagnosed with incident chronic myelogenous leukemia (CML) newly initiating therapy with imatinib, dasatinib, or nilotinib. Patients were followed to determine switching and discontinuation rates. Factors associated with switching or discontinuation from index TKI therapy, reasons for discontinuation based on electronic chart notes, and frequency of laboratory monitoring were assessed during the follow-up period. Methods A retrospective cohort study was conducted in chronic myelogenous leukemia patients aged ≥ 18 years who were identified from the Kaiser Permanente Southern California (KPSC) Cancer Registry database during the study time period of 1 January 2007 to 12 December 2013. The index date was defined as the date of the first TKI prescription (imatinib, dasatinib, or nilotinib) identified during the study time period with no prior history of TKI use within 12 months. Patients had to have continuous membership with drug benefit eligibility and no prior history of stem cell transplant (SCT) or other cancers during the 12 months prior to the index date. Baseline characteristics were identified during 12 months prior to the index date and outcomes were identified during the follow-up period after the index date. All patients were followed from index TKI therapy until end of study time period (12 December 2014), death, stem cell transplant, or disenrollment from the health plan unless one of the following occurred first: a patient switched their index therapy, or a patient discontinued their index therapy. Forward stepwise selection multivariable logistic regression models were used to evaluate factors associated with patients who continued therapy compared to those who switched or discontinued therapy with the index TKI. Chart notes were reviewed 30 days prior and 30 days post index TKI discontinuation to evaluate reasons for discontinuation. Molecular and cytogenetic testing frequency was also assessed during the follow-up period among the different patient groups. Results Two hundred sixteen patients were identified with incident chronic myelogenous leukemia and use of TKI therapy: 189 (87.5%) received imatinib, 19 (8.8%) received dasatinib, and 8 (3.7%) received nilotinib. The mean age on index date was 53 years and 63% were male; 103 patients (48%) continued on their index therapy, while 62 patients (28%) switched, and 51 patients (24%) discontinued.

Warfarin Management and Outcomes in Patients with Nonvalvular Atrial Fibrillation Within an Integrated Health Care System.

BACKGROUND: Warfarin is a common treatment option to manage patients with nonvalvular atrial fibrillation (NVAF) in clinical practice. Understanding current pharmacist-led anticoagulation clinic management patterns and associated outcomes is important for quality improvement; however, currently little evidence associating outcomes with management patterns exists. OBJECTIVES: To (a) describe warfarin management patterns and (b) evaluate associations between warfarin treatment and clinical outcomes for patients with NVAF in an integrated health care system. METHODS: A retrospective cohort study was conducted among NVAF patients with warfarin therapy between January 1, 2006, and December 31, 2011, using Kaiser Permanente Southern California data, and followed until December 31, 2013. Management patterns related to international normalized ratio (INR) monitoring, anticoagulation clinic pharmacist intervention (consultation), and warfarin dose adjustments were investigated along with yearly attrition rates, time-in-therapeutic ranges (TTRs), and clinical outcomes (stroke or systemic embolism and major bleeding). Descriptive statistics and multivariable Cox proportional hazard models were used to determine associations between TTR and clinical outcomes. RESULTS: A total of 32,074 NVAF patients on warfarin treatment were identified and followed for a median of 3.8 years. About half (49%) of the patients were newly initiating warfarin therapy. INR monitoring and pharmacist interventions were conducted roughly every 3 weeks after 6 months of warfarin treatment. Sixty-three percent of the study population had ≥ 1 warfarin dose adjustments with a mean (SD) of 6.7 (6.3) annual dose adjustments. Warfarin dose adjustments occurred at a median of 1 day (interquartile ranges [IQR] 1-3) after the INR measurement. Yearly attrition rate was from 3.3% to 6.3% during the follow-up, and median (IQR) TTR was 61% (46%-73%). Patients who received frequent INR monitoring (≥ 27 times per year), pharmacist interventions (≥ 24 times per year), or frequently adjusted warfarin dose (≥ 11 times per year) consistently showed poor TTRs (mean TTR for the highest quartiles was 45.3%-48.3%). A higher TTR was associated with a lower risk of clinical outcomes regardless of frequency of INR monitoring, pharmacist interventions, or number of dose adjustments. Patients whose TTRs were < 65%, even with frequent pharmacist interventions, had similar stroke or systemic embolism event rates, as compared with patients with TTRs < 65% and less frequent interventions (1.88 vs. 1.54 stroke or systemic embolism rates per 100 person-years, respectively, P = 0.78). The lowest TTR quartile (< 46%) was associated with a 3 times higher risk of stroke or systemic embolism (hazard ratio [HR] = 3.19, 95% CI = 2.71-3.77) and a 2 times higher risk of major bleeding (HR = 2.10, 95% CI = 1.96-2.24) compared with the highest TTR quartile (≥ 73%). CONCLUSIONS: Despite close monitoring with timely warfarin dose adjustments, there were still a substantial number of challenging patients whose TTRs were suboptimal despite a higher number of pharmacist interventions. These patients eventually experienced more stroke or systemic embolism and bleeding events among NVAF patients managed by anticoagulation clinics. New individualized treatment or management strategies for patients who are not able to reach optimal therapeutic ranges are necessary to improve outcomes. DISCLOSURES: This research and manuscript were funded by Bristol-Myers Squibb Company and Pfizer. Authors from Bristol-Myers Squibb Company and Pfizer participated in the design of the study, interpretation of the data, review/revision of the manuscript, and approval of the final version of the manuscript. An received a grant for research support from Bristol-Myers Squibb/Pfizer. Niu, Rashid, and Zheng received a grant from Bristol-Myers Squibb/Pfizer to their institutions for salary reimbursement. Vo, Singh, and Aranda are employed by Bristol-Myers Squibb; Bruno was employed by Bristol-Myers Squibb at the time of this study. Mendes and Dills are employed by Pfizer, and Mendes was a member of the Pfizer Cardiovascular and Metabolic Field Medical Team during the time of this study. Lang, Jazdzewski, and Le have no known conflicts of interest to report. Study concept and design were contributed primarily by An and Rashid, along with the other authors. Niu took the lead in data collection, along with Zheng, and data interpretation was performed by An, along with Mendes and Dills, with assistance from the other authors. The manuscript was written by An and revised by Mendes, Dills, Vo, Singh, Bruno, and Aranda, along with Lang, Le, and Jazdezewski. Part of this study's findings was presented at the CHEST 2015 Annual Meeting in Montreal, Canada, on October 28, 2015.

Primary Nonadherence to Overactive Bladder Medications in an Integrated Managed Care Health Care System.

BACKGROUND: Treatment for overactive bladder (OAB) remains suboptimal, in part because of patient nonadherence to medications. Primary nonadherence is when patients fail to pick up their initial prescriptions. OBJECTIVE: To measure primary nonadherence to OAB medications within 30 days of a first OAB prescription order using electronic medical records from a U.S. managed care health care system METHODS: A retrospective cohort study was conducted using electronic medical records from the Kaiser Permanente Southern California (KPSC) database to identify patients with new OAB prescriptions between January 1, 2007, and December 31, 2013. The index date was defined as the first order of an OAB prescription. Patients had to be aged ≥ 18 years on the index date and were required to have 12 months of continuous membership with drug benefit eligibility before, during, and after the index date. Patients were defined as primary nonadherent if they did not pick up their new OAB prescriptions within 30 days of the order date. Descriptive statistics and a multivariable logistic regression analysis with backward selection were conducted to identify factors associated with patients who were primary nonadherent versus adherent. RESULTS: There were 9,050 patients with a new OAB prescription order; 1,662 (18%) of these were primary nonadherent. Patients with primary nonadherence were younger in age (56.9 [SD ± 16.0] years vs. 63.9 [SD ± 14.8] years; P < 0.001) and more likely to have commercial insurance (65.9% vs. 46.2%; P < 0.001). They also had lower mean Charlson Comorbidity Index (CCI) scores (1.99 vs. 2.70; P < 0.001), fewer OAB-related comorbidities, fewer concomitant medications (P < 0.005), and fewer overall prescriptions dispensed in the previous 12 months (P < 0.001) compared with adherent patients. Significant factors such as commercial insurance (P = 0.013), race other than white (P = 0.020), CCI = 0 versus CCI ≥ 2 (P = 0.001), urinary tract infections (P < 0.001), and falls (P = 0.047) were associated with a higher likelihood of primary nonadherence versus adherence. CONCLUSIONS: Nearly 1 in 5 patients did not pick up their new OAB medications within 30 days of the order date. Knowledge of factors associated with primary nonadherence may inform strategies for improving management of OAB. DISCLOSURES: This study was supported by a research grant provided by Astellas Pharma Global Development. Rashid and Lin do not have any financial interests or potential conflict of interest with regard to the work. Vassilakis, Kristy, and Ng were employees of Astellas Pharma Global Development when this study was conducted. Study concept and design were contributed by Rashid and Ng, along with the other authors. Rashid and Lin collected the data, and data interpretation was performed by Rashid, Ng, and Lin, along with Vassilakis and Kristy. The manuscript was written by Rashid and Ng, along with Vassilakis and Lin, and revised by Rashid, Ng, and Lin.

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.

Economic burden related to chemotherapy-related adverse events in patients with metastatic breast cancer in an integrated health care system.

BACKGROUND: Breast cancer is treated with many different modalities, including chemotherapy that can be given as a single agent or in combination. Patients often experience adverse events from chemotherapy during the cycles of treatment which can lead to economic burden. OBJECTIVE: The objective of this study was to evaluate costs related to chemotherapy-related adverse events in patients with metastatic breast cancer (mBC) in an integrated health care delivery system. METHODS: Patients with mBC newly initiated on chemotherapy were identified and the first infusion was defined as the index date. Patients were ≥18 years old at time of index date, had at least 6 months of health plan membership and drug eligibility prior to their index date. The chemotherapy adverse events were identified after the index date and during first line of chemotherapy. Episodes of care (EOC) were created using healthcare visits. Chart review was conducted to establish whether the adverse events were related to chemotherapy. Costs were calculated for each visit, including medications related to the adverse events, and aggregated to calculate the total EOC cost. RESULTS: A total of 1,682 patients with mBC were identified after applying study criteria; 54% of these patients had one or more adverse events related to chemotherapy. After applying the EOC method, there were a total of 5,475 episodes (4,185 single episodes [76.4%] and 1,290 multiple episodes [23.6%]) related to chemotherapy-related adverse events. Within single episodes, hematological (1,387 EOC, 33.1%), musculoskeletal/pain related (1,070 EOC, 25.6%), and gastrointestinal (775 EOC, 18.5%) were the most frequent adverse events. Patients with adverse events related to single EOC with anemia and neutropenia had the highest total outpatient costs with 901 EOC ($81,991) and 187 EOC ($17,017); these patients also had highest total inpatient costs with 46 EOC ($542,798) and 16 EOC ($136,768). However, within multiple episodes, hematological (420 EOC, 32.6%), followed by infections/pyrexia (335 EOC, 25.9%) and gastrointestinal (278 EOC, 22.6%) were the most frequent adverse events. CONCLUSION: The economic burden related to chemotherapy adverse events in patients with mBC is substantial.

Severe hypertriglyceridemia and factors associated with acute pancreatitis in an integrated health care system.

OBJECTIVE: To evaluate patient characteristics, treatment patterns, comorbidities, and risk factors associated with the development of acute pancreatitis (AP) in patients with severe hypertriglyceridemia (HTG) in an integrated health care delivery system. METHODS: We identified a retrospective cohort of severe HTG patients with a fasting triglyceride level ≥ 1000 mg/dL during January 1, 2007 to June 30, 2013 (index date) in an integrated health care delivery system. Patients were aged ≥18 years on index date and had 12 months of continuous membership and drug eligibility before the index date and during postindex including index date. Baseline patient characteristics, comorbidities, and risk factors were evaluated during 12-month preindex. Outcomes such as development of AP, treatment patterns, adherence to index therapy, and change in triglyceride (TG) laboratory levels were evaluated during postindex. Descriptive statistics were used to identify differences between patients developing AP vs no development of AP. A stepwise multivariate logistic regression and backward elimination method were used to assess statistically significant predictive factors associated with development of AP vs no AP. RESULTS: We identified 5550 patients with severe HTG, and 5.4% of these patients developed AP during postindex. Patients were mostly male (≥70%) in both groups; however, younger in the AP group (45 years ± 10.6) vs no AP group (50 years ± 11.4) with P value < .0001. The AP group had higher baseline Charslon Comorbidity Index score, alcohol abuse history (42.2%), any pancreatitis history (51.5%), diabetes (47%), and hypertension (55%), vs the no AP group (P values < .05). Patients in the AP group had higher baseline mean TG levels (2148, SD ± 1578) vs the no AP group (1559, SD ± 861), P value < .0001. Over 50% of the patients were prescribed their index therapy by a primary care provider. Predictive factors associated with the development of AP included younger age, alcohol use, and prior history of any pancreatitis, hypertension, renal disease stage 4, and other prescriber specialty. From parameters estimates, for each 100 mg/dL unit of increase in the TG level above 1000 mg/dL, there was a 3 percent increase in risk of developing AP. CONCLUSIONS: Patients with severe HTG are at a higher risk of developing AP. A number of comorbidities, risk factors, and baseline TG levels are associated with an increased incidence of AP. Patients with severe HTG are underdiagnosed, undertreated and are nonadherent to their index lipid therapy. There is a need to better define optimal approaches to treating severe HTG so as to reduce the incidence of AP. Economic studies are also needed to evaluate the burden of AP on various health care systems.

Rates, factors, reasons, and economic impact associated with switching in rheumatoid arthritis patients newly initiated on biologic disease modifying anti-rheumatic drugs in an integrated healthcare system.

Objectives To identify how many RA patients newly-initiated on bDMARD therapy switch to another bDMARD during the first year of treatment; to evaluate the factors and reasons associated with bDMARD switching; and to compare the RA-related healthcare resource utilization (HCRU) and costs between switchers vs non-switchers during the post-index period. Methods A retrospective cohort study was conducted in RA patients using the Kaiser Permanente Southern California (KPSC) database with the study time period of January 1, 2007 to December 31, 2012. The index date was defined as the date of the first bDMARD prescription. Patients had to have continuous membership eligibility with drug benefit and no prior history of bDMARD during the 24 months prior to the index date. bDMARD switching was defined as a different bDMARD claim during post-index. A multivariable logistic regression model was used to evaluate factors associated with switchers vs non-switchers. Chart notes were reviewed to evaluate reasons for switching from index bDMARD. RA-related HCRU use and costs were evaluated using a generalized linear model (GLM) with gamma distribution and log link function. Results Two hundred and fifty-one patients (12%) switched from their index bDMARD to a different bDMARD during the post-index period. bDMARD switchers were more likely to be female, of Asian/Pacific race, younger than ≤65 years of age, overweight, CCI score ≤2, initiating etanercept or adalimumab, and have a commercial insurance plan compared to non-switchers. Reasons for switching were related mostly to lack or loss of efficacy (∼51%); bDMARD switchers had overall mean adjusted RA related total costs that were 25% higher (p = 0.04) compared to non-switchers. Conclusion It is important for RA patients to receive appropriate therapy and consider bDMARD with different mechanisms of action to decrease subsequent switching, and decrease overall RA related costs as shown in this study.

Clinical Impact of Chemotherapy-Related Adverse Events in Patients with Metastatic Breast Cancer in an Integrated Health Care System.

BACKGROUND: Stage IV breast cancer, also known as metastatic breast cancer (mBC), is not a curable condition. However, treatment can prolong life, delay the progression of the cancer, or improve quality of life. Currently, patients with mBC are often treated with chemotherapy. Patients often experience adverse events from chemotherapy during the treatment cycle, which leads to chemotherapy modifications such as dose delay, dose reduction, or discontinuation of chemotherapy. Previous studies have evaluated the rates of adverse events that occur from the use of chemotherapy; however, few studies have evaluated the clinical impact on the chemotherapy regimen once the adverse event occurs. This study evaluates the clinical impact on the chemotherapy regimen from chemotherapy-related adverse events in patients with mBC in an integrated health care delivery system.   OBJECTIVES: To assess the adverse events in patients with mBC and evaluate the clinical impact on the chemotherapy regimen from these adverse events in an integrated health care delivery system.  METHODS: This study is a retrospective cohort of patients with mBC newly initiated on chemotherapy. The first infusion was defined as the index date. Patients were aged greater than 18 years at time of index date and had 6 months or more of Kaiser membership and drug eligibility prior to the index date and continuous membership and drug eligibility throughout follow-up. Adverse events were identified after the index date and during the follow-up using ICD-9-CM diagnosis and procedure codes. Single or multiple episodes of care were created from the adverse events. Chart review was conducted to establish whether the adverse event was related to chemotherapy and if any modification to the chemotherapy regimen occurred-a dose delay, dose reduction, or discontinuation was considered a clinical impact on therapy. Multivariate logistic regression was used to examine factors associated with clinical impact versus no clinical impact from the delivery of chemotherapy treatment.  RESULTS: A total of 1,682 patients with mBC were identified during our time period with an average follow-up of 2.21 years on first-line chemotherapy (SD = 1.83). 909 patients (54%) had at least 1 adverse event, and 773 patients (46%) did not have any adverse events during follow-up. Significant differences at baseline between these 2 groups included race, peripheral vascular disease, and length of stay (P less than 0.05). From the 909 patients who had at least 1 adverse event, 185 patients (20%) experienced an impact on their chemotherapy regimens. Patients with single episodes of care with any chemotherapy regimen impact experienced mostly hematological, infection/pyrexia, and gastrointestinal-related adverse events. In multiple episodes of care, neurological impact was more frequent than gastrointestinal-related effects. Patients with hospitalizations of greater than 3 days experienced the most impact, demonstrating that severe adverse events have more impact on chemotherapy regimens. In our multivariate analysis, patients aged greater than 65 years, having more than 1 comorbidity and having longer duration in days for each episode of care were all associated with clinical impact. Black and Hispanic patients were more likely to have a modification in their chemotherapy compared with white patients. CONCLUSIONS: This retrospective analysis demonstrates that chemotherapy-related adverse events in patients with mBC have an impact on the delivery of chemotherapy regimens. Having multiple comorbidities, increased age, and prolonged hospitalizations because of adverse events appear to be some of the primary factors related to chemotherapy modification.

Medication Extraction from Electronic Clinical Notes in an Integrated Health System: A Study on Aspirin Use in Patients with Nonvalvular Atrial Fibrillation.

PURPOSE: The purpose of this study was to investigate whether aspirin use can be captured from the clinical notes in a nonvalvular atrial fibrillation population. METHODS: A total of 29,507 patients with newly diagnosed nonvalvular atrial fibrillation were identified from January 1, 2006, through December 31, 2011, and were followed up through December 31, 2012. More than 3 million clinical notes were retrieved from electronic medical records. A training data set of 2949 notes was created to develop a computer-based method to automatically extract aspirin use status and dosage information using natural language processing (NLP). A gold standard data set of 5339 notes was created using a blinded manual review. NLP results were validated against the gold standard data set. The aspirin data from the structured medication databases were also compared with the results from NLP. Positive and negative predictive values, along with sensitivity and specificity, were calculated. FINDINGS: NLP achieved 95.5% sensitivity and 98.9% specificity when compared with the gold standard data set. The positive predictive value was 93.0%, and the negative predictive value was 99.3%. NLP identified aspirin use for 83.8% of the study population, and 70% of the low dose aspirin use was identified only by the NLP method. IMPLICATIONS: We developed and validated an NLP method specifically designed to identify low dose aspirin use status from the clinical notes with high accuracy. This method can be a valuable tool to supplement existing structured medication data.

Patient and clinical characteristics associated with gout flares in an integrated healthcare system.

Gout flares have been challenging to identify in retrospective databases due to gout flares not being well documented by diagnosis codes, making it difficult to conduct accurate database studies. Previous studies have used different algorithms, and in this study, we used a computer-based method to identify gout flares. The objectives of this study were to identify gout flares in gout patients newly initiated on urate-lowering therapy and evaluate factors associated with a patient experiencing gout flares after starting drug treatment. This was a retrospective cohort study identifying gout patients newly initiated on a urate-lowering therapy (ULT) during the study time period of January 1, 2007-December 31, 2010. The index date was the first dispensed ULT prescription during the study time period. Patients had to be ≥18 years of age on index date, have no history of prior ULT prescription during 12 months before index date, and were required to have 12 months of continuous membership with drug benefit during pre-/post-index. Electronic chart notes were reviewed to identify gout flares; these reviews helped create a validated computer-based method to further identify patients with gout flares and were categorized into 0 gout flares, 1-2 gout flares, and ≥3 gout flares during the 12 months post-index period. Multivariable logistic regression was used to examine patient and clinical factors associated with gout flares during the 12-month follow-up period. There were 8905 patients identified as the final cohort and 68 % of these patients had one or more gout flares during the 12-month follow-up: 2797 patients (31 %) had 0 gout flares, 4836 (54 %) had 1-2 gout flares, and 1272 patients (14 %) had ≥3 gout flares. Using a multivariate regression analyses, factors independently associated with 1-2 gout flares and ≥3 gout flares versus no gout flares were similar, however, with slight differences, such as younger patients were more likely to have 1-2 gout flares and patients ≥65 years of age had ≥3 gout flares. Factors such as male gender, not attaining sUA goal, having ≥3 comorbidities, diuretics use, no changes in initial ULT dose, and not adhering to ULT all were associated with gout flares versus no gout flares. Using a new method to identify gout flares, we had the opportunity to compare our findings with the previous studies. Our study findings echo other previous studies where older patients, male, diuretics, having a greater number of comorbidities, and non-adherence are more likely to have more gout flares during the first year of newly initiating ULT. There is an unmet need for patients with gout to be educated and managed more closely, especially during the first year.

A Descriptive Evaluation of Prescriber Perceptions and Experience With Risk Evaluation and Mitigation Strategy (REMS) Programs in an Integrated Health Care System.

OBJECTIVE: To assess prescriber perceptions and experience with risk evaluation and mitigation strategy (REMS) programs in an integrated health care delivery system. METHODS: A cross-sectional online survey was e-mailed to eligible health care prescribers if they prescribed at least 1 selected REMS-related product within 6 months spanning January 1 to June 30, 2013; were an active employee of Kaiser Permanente Southern California; and had an active " kp.org " e-mail address. Descriptive analyses were conducted on the survey responses. RESULTS: Three hundred sixty-four respondents (34%) completed the online survey. The majority were primary care prescribers (65%) versus nonprimary prescribers. The majority of primary care, oncologist, and specialist prescribers responded that REMS was meaningful, improved patient safety, and made an impact on their patient interactions. The majority of surgeons and pain management prescribers responded that REMS was not meaningful, did not improve safety for the patients, or did not impact their interactions with their patients. Over 50% of prescribers counseled their patients or had another health care team member discuss the risks and benefits of these REMS-related medications; medication guides or other printed literature was not provided as much. CONCLUSION: The results from the survey suggest that prescriber specialty has an impact on the perceived value of the REMS program and the perceived need to counsel patients regarding medications with REMS programs.

Modifiable factors associated with allopurinol adherence and outcomes among patients with gout in an integrated healthcare system.

OBJECTIVE: To identify modifiable patient and provider factors associated with allopurinol adherence and the achievement of a serum urate acid (SUA) goal in gout. METHODS: We identified a retrospective cohort of patients with gout, newly treated with allopurinol. All patient data came from administrative datasets at a large integrated health delivery system. Patients were ≥ 18 years old at time of initial allopurinol dispensing, and had 12 months or more of membership and drug eligibility prior to the index date. Allopurinol adherence was defined as a proportion of days covered ≥ 0.80, evaluated during the first 12 months of observation after the initial dispensing. Multivariable logistic regression was used to examine factors associated with allopurinol nonadherence and attaining an SUA concentration < 6.0 mg/dl. RESULTS: We identified 13,341 patients with gout with incident allopurinol use (mean age 60 yrs, 78% men). Of these, 9581 patients (72%) had SUA measured both at baseline and during followup. Only 3078 patients (32%) attained an SUA target of < 6.0 mg/dl during followup. Potentially modifiable factors associated with treatment adherence and obtaining the SUA goal in the multivariable analysis included concomitant diuretic use, prescriber specialty, and allopurinol dosing practices. Adherent patients were 2.5-fold more likely than nonadherent patients to achieve an SUA < 6.0 mg/dl during observation. CONCLUSION: Among patients with gout initiating allopurinol in our study, 68% did not reach the SUA goal and 57% of patients were nonadherent. Modifiable factors, including allopurinol dose escalation, treatment adherence, rheumatology referral, and concomitant medication use, could be important factors to consider in efforts aimed at optimizing gout treatment outcomes.

Switching to Omnitrope(®) from Other Recombinant Human Growth Hormone Therapies: A Retrospective Study in an Integrated Healthcare System.

INTRODUCTION: This study was conducted using an integrated retrospective database to evaluate the effectiveness of Omnitrope(®) (Sandoz) on children with growth hormone deficiency (GHD), idiopathic short stature (ISS), and Turner Syndrome (TS) who switched from a non-Omnitrope recombinant human growth hormone (rhGH) preparation during routine clinical care. METHODS: This was a retrospective study which identified patients with GHD, ISS, and TS during the study time period of January 1, 2006 and July 31, 2011. Patients were included if they switched to Omnitrope from another non-Omnitrope rhGH therapy during the study time period, were <18 years of age at time of switch, and on a prior rhGH therapy for at least 15 months pre-switch and on Omnitrope for 15 months post-switch. Auxological parameters (height, height standard deviation score [HSDS], height velocity [HV], and height velocity standard deviation score [HVSDS]) were evaluated during post-switch. RESULTS: One hundred and three patients were identified: GHD (n = 57), ISS (n = 26), and TS (n = 20). There was continuous growth in height for all 103 patients with an average rate of 6.52 cm over the 15-month post-switch period. Patients with GHD grew an average rate of 6.30 cm, patients with ISS grew an average rate of 6.58 cm, and patients with TS grew an average rate of 6.52 cm over the 15-month post-switch period. The average rate of HSDS was increased by 0.04 for all patients. The HV and HVSDS demonstrated the expected decline with advancing age and prolonged duration of treatment. CONCLUSIONS: The growth trajectories of rhGH-treated patients were not negatively impacted by switching to Omnitrope and growth rates remained as expected prior to the switch.