Clinical Factors Associated With Nonadherence to Chronic Medications in People With Cognitive Impairment.

Objective To study assessed adherence to 11 chronic medications and one medication class with high medical necessity in people with cognitive impairment (CIM) and identified clinical characteristics associated with nonadherence. Design This was a retrospective cohort study. 180-day adherence was calculated as the percent of days covered (PDC). Multi-variable logistic regression modeling was used to identify clinical factors associated with a PDC less than 80% (ie, nonadherence) to one or more studied chronic medication(s). Setting Primary care in an integrated health care delivery system. Patients People with CIM 65 years of age or older who were dispensed five or more chronic medications in one month between March 1, 2019, and October 31, 2019. Results Overall, the 1,109 patients included were older (mean age = 79.8 years of age), female (54.1%), White (78.6%), had a high burden of chronic disease, and 396 (35.7%) were nonadherent to one or more study medication(s). Two medications (tiotropium and venlafaxine) and one medication class (direct oral anticoagulants) had a mean PDC less than 80%. Alzheimer's disease and related dementias (ADRD), chronic pain, chronic obstructive pulmonary disease (COPD), male, nonwhite race, and one or more mental health visits were associated independently with nonadherence. Conclusions Chronic pain, COPD, ADRD, male sex, nonwhite race, and mental health care use were associated with nonadherence. These findings can help guide clinicians as they navigate medication therapy in people with CIM.

Clinical outcomes of dabigatran use in patients with non-valvular atrial fibrillation and weight >120 kg.

BACKGROUND: Patients with obesity were underrepresented in studies evaluating the safety and effectiveness of direct oral anticoagulants (DOAC) in patients with non-valvular atrial fibrillation (NVAF). This study compared clinical outcomes in patients with NVAF and weighing >120 kg and ≤120 kg who were receiving dabigatran. MATERIALS AND METHODS: This retrospective, matched, longitudinal cohort study included patients from three integrated healthcare delivery systems. Patients ≥18 years of age with NVAF were included if between September 1, 2016 and June 30, 2019 they received dabigatran. Patients >120 kg and ≤120 kg were matched up to 1:6 on age, sex, and CHA2DS2-VASc score. Data were extracted from administrative databases. The primary outcome was a composite of ischemic stroke, clinically-relevant bleeding, systemic embolism, and all-cause mortality. Multivariable regression analyses were performed. RESULTS: 777 and 3522 patients >120 kg and ≤120 kg, respectively, were matched. The >120 kg group tended to be younger with a higher burden of chronic disease. There was no difference between groups in the composite outcome (adjusted hazard ratio [AHR] 1.10, 95% confidence interval 0.89-1.37) or individual components of the composite. A subanalysis of clinically-relevant bleeding identified that patients >120 kg were at a greater risk of gastrointestinal bleeding (AHR 1.44, 95% CI 1.01-2.05). CONCLUSIONS: In patients with NVAF and >120 kg, dabigatran use was associated with a small increased risk of gastrointestinal bleeding but no differences in stroke, mortality or clinically-relevant bleeding. These findings suggest that dabigatran use is reasonable in patients with NVAF and weight >120 kg.

Retrospective assessment of antimicrobial stewardship initiative in outpatient use of ertapenem for uncomplicated extended spectrum beta lactamase Enterobacteriaceae urinary tract infections.

BACKGROUND: Urinary tract infections (UTI) are often over-diagnosed and over-treated, which can induce and select for resistant pathogens. After observing wide-spread outpatient use of ertapenem, a broad-spectrum antibiotic, a structured antimicrobial stewardship initiative (ASI) to improve appropriate antimicrobial prescribing was undertaken. ASI objectives were to achieve a goal of reducing ertapenem utilization for extended spectrum beta lactamase Enterobacteriaceae (ESBL-EB) UTI by 10% and evaluate the clinical outcomes associated with the ASI. METHODS: A pre-to-post cohort study was conducted at a single-center integrated healthcare system between November 1, 2014 and February 26, 2017. An intensive, 90-day, pharmacist-driven, structured ASI was implemented between November 1, 2015 and January 29, 2016. Female patients aged ≥18 years who were treated for an uncomplicated, ESBL-EB urinary tract infection (UTI) were included. Primary outcome was clinical resolution defined as cure, persistence, relapse and recurrence. Secondary outcome measured was monthly ertapenem use expressed as number of days of therapy (DOT)/1000 adjusted patient days (APD). Segmented regression analysis for interrupted time series was performed to estimate ASI intervention effect. RESULTS: A total of 184 patients were included in the study. Ertapenem utilization decreased from 0.0145 DOT/1000 APD in Nov. 2014 to 0.0078 DOT/1000 APD Feb. 2017(p < 0.01). The mean ertapenem DOT declined 19% overall from the pre vs. post intervention periods (32 vs 26, p < 0.01). Frequency of recurrent UTIs between treatments did not significantly differ and no adverse effects were reported in patients treated with aminoglycosides. CONCLUSIONS: A structured ASI for uncomplicated ESBL-EB UTI was associated with a clinically meaningful decrease in ertapenem utilization and once-daily, 5-day aminoglycoside treatment was well-tolerated.

Aligning care with the personal values of patients with complex care needs.

OBJECTIVE: To identify opportunities to align care with the personal values of patients from three distinct groups with complex medical, behavioral, and social needs. DATA SOURCES/STUDY SETTING: Between June and August 2019, we conducted semi-structured interviews with individuals with complex care needs in two integrated health care delivery systems. STUDY DESIGN: Qualitative study using semi-structured interviews. DATA COLLECTION METHODS: We interviewed three groups of patients at Kaiser Permanente Washington and Kaiser Permanente Colorado representing three distinct profiles of complex care needs: Group A ("obesity, opioid prescription, and low-resourced neighborhood"), Group B ("older, high medical morbidity, emergency department, and hospital use"), and Group C ("older, mental and physical health concerns, and low-resourced neighborhood"). These profiles were identified based on prior work and prioritized by internal primary care stakeholders. Interview transcripts were analyzed using thematic analysis. PRINCIPAL FINDINGS: Twenty-four patients participated; eight from each complex needs profile. Mean age across groups was 71 (range 48-86) years. We identified five themes common across the three groups that captured patients' views regarding values-aligned care. These themes focused on the importance of care teams exploring and acknowledging a patient's values, providing access to nonphysician providers who have different perspectives on care delivery, offering values-aligned mental health care, ensuring connection to community-based resources that support values and address needs, and providing care that supports the patient plus their family and caregivers. CONCLUSIONS: Our results suggest several opportunities to improve how care is delivered to patients with different complex medical, behavioral, and social needs. Future research is needed to better understand how to incorporate these opportunities into health care.

Clinical Effectiveness of an Outpatient Multidisciplinary Chronic Pain Management Telementoring Service.

OBJECTIVE: The objective of this study was to assess the effectiveness of a Pain E-Consult Program (PEP), a multidisciplinary telementoring service based on the Extension for Community Healthcare Outcomes (ECHO) model to reduce opioid use in the outpatient setting. MATERIALS AND METHODS: This was a retrospective matched cohort study conducted in an integrated health care delivery system. Adult patients without cancer and with a 90-day morphine milligram equivalent (MME) ≥30 mg/d between April 1, 2016, and June 30, 2017, were included. Patients whose primary care clinician received the PEP (observation) were compared with usual care (control) patients. Observation patients were matched up to 1:5 to control patients. Outcomes included change in MME and initiation of nonopioid alternative medications. Multivariable regression analyses were performed. RESULTS: A total of 665 patients were matched: 125 and 540 in the observation and control groups, respectively. Patients were primarily female, white, and Medicare beneficiaries. The observation group had a statistically significantly greater decrease in median MME/day during the 6-month (-7.4 vs. 1.5 mg, P=0.002) and 12-month (-15.1 vs. -2.8 mg, P<0.001) follow-up and rates of ≥20% decrease (6 mo: 41.6% vs. 24.6%, P=0.003; 12 mo: 48.0% vs. 32.6%, P=0.017). There were no differences in the rates of initiation of nonopioid alternative medications. CONCLUSIONS: A PEP was associated with greater reductions in MME/day compared with usual care despite similar rates of nonopioid alternative medication initiation. A prospective randomized study of this program should be undertaken to confirm these findings.

Retrospective Cohort Study Comparing Infliximab-dyyb and Infliximab in Biologic-Naive Patients With Inflammatory Bowel Disease in the United States.

Background: Real-world assessments of biosimilars are needed to understand their effectiveness and safety in practice settings that may differ from those seen in clinical trials or healthcare systems in different countries. To assess the effectiveness and safety of a biosimilar (infliximab-dyyb) and its reference product (infliximab) in patients with inflammatory bowel disease (IBD) in the United States. Methods: We conducted a retrospective cohort study of biologic-naive patients with IBD who started treatment with infliximab-dyyb or infliximab. The study included 3206 patients identified through electronic health records in a US integrated healthcare delivery system. The effectiveness outcome was a composite of IBD-related surgery, IBD-related emergency room visit, and IBD-related hospitalization within 12 months of initiation. Safety outcomes included incidence of any or serious infection, cancer, acute liver dysfunction, and tuberculosis. We used a non-inferiority test with an upper-limit margin of 10% to analyze effectiveness. Doubly robust methods incorporating Cox proportional hazard regression with standardized inverse probability of treatment weighting were used to analyze both effectiveness and safety outcomes. Results: The composite effectiveness outcome occurred in 107 of 870 patients (12.3%) in the infliximab-dyyb and 379 of 2336 patients (16.2%) in the infliximab groups. Infliximab-dyyb was non-inferior (P < .01) and was not different (hazard ratio [HR] 0.81; confidence interval [CI] 0.65-1.01; P = .06) to infliximab. Safety outcomes were not different between infliximab-dyyb and infliximab for any infections (HR 1.01; CI 0.86-1.17; P = .95), serious infections (HR 0.83; CI 0.54-1.26; P = .38), cancers (HR 0.83; CI 0.44-1.54; P = .55), and tuberculosis (HR 0.59; CI 0.10-3.55; P = .57). Conclusions: Initiation of infliximab-dyyb was non-inferior to infliximab among biologic-naive patients with IBD in an US integrated healthcare delivery system.

Patterns of Care and Treatment Outcomes for Outpatient Daptomycin-Containing Regimens in Osteomyelitis.

BACKGROUND: Use of daptomycin at doses ≥ 6 mg/kg for treatment of osteomyelitis is increasing in clinical practice; unfortunately, limited data are available to guide optimal dosing and duration. The objective of this study was to assess daptomycin dosing and duration regimens for osteomyelitis treatment. METHODS: This was a retrospective, multi-site, cohort study conducted in an integrated healthcare delivery system. Nonpregnant patients ≥ 18 years of age with osteomyelitis diagnosed between November 1, 2003 and June 30, 2011, ≥ 2 weeks outpatient daptomycin therapy, and ≥ 1 month of follow-up were included. Daptomycin doses < 6 mg/kg and ≥ 6 mg/kg at durations of < 6 weeks and ≥ 6 weeks were examined with univariate and multivariate analyses to assess treatment success and all-cause mortality. RESULTS: A total of 247 patients were included, with 39 (15.8%), 37 (15.0%), 107 (43.3%), and 64 (25.9%) receiving < 6 mg/kg and ≥ 6 weeks, < 6 mg/kg and < 6 weeks, ≥ 6 mg/kg and ≥ 6 weeks, and ≥ 6 mg/kg and < 6 weeks of daptomycin therapy, respectively. Patients had a mean age of 58 years and had received prior vancomycin therapy (65.6%). Patients receiving < 6 weeks of therapy were less likely to experience treatment success compared with ≥ 6 weeks (41.5% vs 25.3%, adjusted odds ratio = 0.55; 95% confidence interval = 0.31-0.98) independent of duration. There were no differences across groups in mortality after adjustment. CONCLUSION: In a diverse clinical population, daptomycin for treatment of osteomyelitis of 6 weeks or longer duration was associated with success independent of dose. This finding supports longer treatment with daptomycin as a first-line agent in antimicrobial stewardship initiatives.

Perceptions of the Value of Clinical Pharmacy Medication Review for Women During Early Pregnancy.

BACKGROUND: The benefit of continuing medications to prevent or treat illness is often overlooked, since pregnant women tend to overestimate the teratogenic risk of medications. Pharmacists can serve as a resource to prescribers and pregnant women with their knowledge of the appropriate use and management of medications during pregnancy. Little information exists on the value women place on pharmacists' medication management during pregnancy. OBJECTIVE: To assess pregnant women's perceptions of an ambulatory care clinical pharmacist (CP) medication review service during early pregnancy that provided education regarding the risks and benefits of medication use during pregnancy. METHODS: This was a qualitative study of pregnant women using semistructured telephone interviews performed between December 12, 2018, and January 18, 2019, and conducted in an integrated health care delivery system. Potential participants were identified from CP encounter records. Consented English-speaking women aged ≥ 18 years participated in an up to 30-minute interview within 1 week of the CP encounter. Interviews were professionally transcribed and coded line by line using the constant comparison method with grounded theory used to gain insight into participants' perspectives. RESULTS: 62 women were invited to participate in semistructured telephone interviews of whom 24 (39%) completed the interview. Three main themes emerged from the qualitative analysis: satisfaction with the service, comfort with medication use during pregnancy, and connectedness to the health care team. Overall, the CP medication review and education service was perceived positively by the participants. Participants reported satisfaction in the quality, timeliness, and convenience of the service and found it beneficial to have their medications reviewed early during pregnancy to assist in medication use decisions before their first obstetric visit. CONCLUSIONS: CP medication review provided a comforting, valuable service for women during early pregnancy when medication-taking decisions can feel exigent. DISCLOSURES: This study was funded by Kaiser Permanente. The authors have nothing to disclose. Preliminary results were presented at the Mountain States Conference for Residents and Preceptors, May 2019, in Salt Lake City, UT.

Temporal trends in first-line outpatient anticoagulation treatment for cancer-associated venous thromboembolism.

BACKGROUND: First-line treatment and secondary prevention of venous thromboembolism (VTE) in patients with cancer consisted, historically, of unfractionated heparin or low-molecular weight heparin (LMWH). With recent clinical trials of direct oral anticoagulants (DOAC) showing similar efficacy as LMWH, little is known about anticoagulant prescribing patterns in patients with cancer and a VTE. This study characterized the temporal trends in first-line outpatient anticoagulation therapy for cancer-associated VTE. MATERIALS AND METHODS: This retrospective cohort study of patients who were hospitalized for a cancer-associated venous thromboembolism (VTE) between 01/01/2000 and 10/31/2017 identified patients from the cancer registries at two regions of an integrated healthcare delivery system. The primary outcome was the trend in age- and sex-adjusted rates of first-line anticoagulant therapy during the 30 days post-hospital discharge. Therapies were categorized as 1) injectable LMWH monotherapy, 2) warfarin ± injectable, 3) injectable fondaparinux monotherapy, or 4) DOAC ± injectable. RESULTS: Overall, 9816 patients were included with a mean age of 66 ± 13 years and 54% were female. From 2000 to 2003, warfarin ± injectable was used in ≈90% of cases. After 2003, there was a steady decline in warfarin use (25% in 2017) corresponding with increased LMWH use: 11% in 2003 to 55% in 2017. The DOAC ± injectable use has rapidly increased from <1% in 2014 to 20% in 2017. CONCLUSIONS: From 2000 to 2017, first-line anticoagulant therapy for cancer-associated VTE has experienced a substantial increase in LMWH and DOAC use with a resultant decline in warfarin use.

Indications for Rituximab Use in an Integrated Health Care Delivery System.

BACKGROUND: Rituximab is a top-selling biologic that was first approved by the FDA in 1997 for a non-Hodgkin lymphoma orphan indication. It has since been approved for additional orphan indications, with rheumatoid arthritis as the only FDA-approved, nonorphan indication. Evidence suggests that rituximab is frequently used off-label, but information on its use over time and indications for use in the United States is limited. OBJECTIVE: To assess incident rituximab use over time in an integrated health care delivery system. METHODS: This was a cross-sectional, retrospective study. Data were collected from administrative databases and manual chart reviews. Patients who received their first rituximab infusion between October 1, 2009, and December 31, 2017, and who were not a part of a clinical trial were included. Indication for use (FDA-approved orphan/nonorphan, off-label) was determined. Proportions of use were assessed over time. Multivariable logistic regression modeling was performed to assess factors associated with receiving rituximab for an FDA-approved indication. RESULTS: A total of 1,674 patients were included. The majority (66.4%) of patients had an FDA-approved indication, with lymphoma being the most common approved indication (66.4%). The most common indication for off-label use was neurologic conditions (72.7%), predominantly demyelinating diseases. Off-label indication use increased from 1.2% in 2009 to 55.6% in 2017. Factors associated with rituximab use for an FDA-approved indication included increased age (adjusted odds ratio [AOR] = 1.05, 95% CI = 1.04-1.07) and increased burden of chronic disease (chronic disease score: AOR = 1.07, 95% CI = 1.02-1.12; Charlson Comorbidity Index score: AOR = 3.52, 95% CI = 3.03-4.10). CONCLUSIONS: Off-label use of rituximab grew dramatically over the course of the study. With the recent FDA approval of the rituximab biosimilar and its expected lower price, off-label use will likely continue to rise. Opportunities for cost savings and to ensure appropriate use of these medications should be evaluated. DISCLOSURES: This study was funded by Kaiser Permanente. All authors except Hansen are employed by Kaiser Permanente. Hansen has nothing to disclose. Preliminary results were presented at the Mountain States Conference for Residents and Preceptors in May 2019 in Salt Lake City, UT, and at an encore presentation October 2019 at the American College of Clinical Pharmacy Annual Meeting in New York, NY.

Validation of algorithms to identify elective percutaneous coronary interventions in administrative databases.

BACKGROUND: Elective percutaneous coronary interventions (PCI) are difficult to discriminate from non-elective PCI in administrative data due to non-specific encounter codes, limiting the ability to track outcomes, ensure appropriate medical management, and/or perform research on patients who undergo elective PCI. The objective of this study was to assess the abilities of several algorithms to identify elective PCI procedures using administrative data containing diagnostic, utilization, and/or procedural codes. METHODS AND RESULTS: For this retrospective study, administrative databases in an integrated healthcare delivery system were queried between 1/1/2015 and 6/31/2016 to identify patients who had an encounter for a PCI. Using clinical criteria, each encounter was classified via chart review as a valid PCI, then as elective or non-elective. Cases were tested against nine pre-determined algorithms. Performance statistics (sensitivity, specificity, positive predictive value, and negative predictive value) and associated 95% confidence intervals (CI) were calculated. Of 521 PCI encounters reviewed, 497 were valid PCI, 93 of which were elective. An algorithm that excluded emergency room visit events had the highest sensitivity (97.9%, 95%CI 92.5%-99.7%) while an algorithm that included events occurring within 90 days of a cardiologist visit and coronary angiogram or stress test had the highest positive predictive value (62.2%, 95%CI 50.8%-72.7%). CONCLUSIONS: Without an encounter code specific for elective PCI, an algorithm excluding procedures associated with an emergency room visit had the highest sensitivity to identify elective PCI. This offers a reasonable approach to identify elective PCI from administrative data.

Vitamin K versus warfarin interruption alone in patients without bleeding and an international normalized ratio > 10.

BACKGROUND: Reversal of an international normalized ratio (INR) > 10 with vitamin K is recommended in patients experiencing bleeding; however, information on outcomes with reversal using vitamin K in non-bleeding patients is lacking. OBJECTIVE: To compare clinical and safety outcomes between non-bleeding patients receiving warfarin with an INR > 10 who did and did not receive a prescription for vitamin K. PATIENTS/METHODS: This was a retrospective cohort study conducted in an integrated health-care delivery system. Adult patients receiving warfarin therapy who experienced an INR > 10 without bleeding between 01/01/2006 and 06/30/2018 were included. Patients were assessed for an outpatient dispensing or in-office administration of vitamin K on the day of or the day after an INR > 10 and then clinically relevant bleeding, thromboembolism, all-cause mortality, and time to INR < 4 within the next 30 days. RESULTS: A total of 809 patients was included with 332 and 477 who were and were not dispensed vitamin K, respectively. Overall, mean patient age was 71.7 years, 60.1% were female and the mean INR was 10.4 at presentation. There were no differences between groups in 30-day rates of bleeding or thromboembolism (both P > .05). Patients dispensed vitamin K had a higher likelihood of mortality (15.1% versus 10.1%, P = .032, adjusted odds ratio = 1.63, 95% confidence interval 1.03 to 2.57). Overall, time to an INR < 4 was similar between groups. CONCLUSION: Vitamin K administration was not associated with improved clinical outcomes in asymptomatic patients with an INR > 10.

Universal hepatitis B screening and management in patients with cancer who received immunosuppressive chemotherapy.

BACKGROUND: Clinical data to guide management of patients with cancer and hepatitis B virus (HBV) infection who are treated with immunosuppressive chemotherapy are lacking. The purpose of this study was to describe HBV+ rates in a population of patients with cancer and evaluate a risk-stratified management protocol for the prevention of HBV reactivation (HBVr). METHODS: This was a descriptive study conducted in an integrated healthcare delivery system. Patients with cancer and hepatitis B virus infection who received immunosuppressive chemotherapy between 1 January 2014 and 31 January 2016 were included. A risk-stratified management protocol that continued for six months after chemotherapy completion or 12 months after completion of B-cell targeted chemotherapy was assessed. Outcomes included the proportion of patients who were HBV+ and amongst patients who initiated immunosuppressive therapy, proportions who received hepatitis B virus monitoring or anti-hepatitis B virus prophylaxis, or experienced HBVr or hepatitis B virus-related complications. RESULTS: There were 2463 patients with cancer screened for hepatitis B virus with 114 (4.6%) HBV+ of whom 59 (51.8%) initiated chemotherapy. Included patients were primarily older, male, and white with gastrointestinal or hematologic cancers and initiated intermediate/low-risk cytotoxic chemotherapy. During follow-up, 41 (69.5%) received hepatitis B virus DNA monitoring and 17 (28.8%) initiated anti-hepatitis B virus prophylaxis. No HBVr was observed. ALT and AST abnormalities were common but mostly Grade 1 and primarily related to the patient's malignancy or medications. CONCLUSIONS: Universal hepatitis B virus screening coupled with a risk-stratified management strategy utilizing HBVr monitoring and anti-hepatitis B virus prophylaxis in HBV+ patients receiving immunosuppressive chemotherapy for cancer may prevent HBVr.

Effectiveness of Best Practice Alerts for Potentially Inappropriate Medication Orders in Older Adults in the Ambulatory Setting.

INTRODUCTION: Information is limited about the effectiveness of best practice alerts (BPAs) for potentially inappropriate medications (PIMs) in improving clinical outcomes in older adults. OBJECTIVE: To assess clinical outcomes of 11 BPAs for PIMs in older adults in the ambulatory setting. METHODS: A retrospective cohort study was conducted at an integrated health care delivery system with computerized provider order entry. Patients aged 65 years and older were included if they had a BPA triggered when a prescriber attempted to order a sedating PIM in the ambulatory setting. Patients were categorized into dispensed and nondispensed groups if they did and did not, respectively, have the study PIM for which the BPA was triggered dispensed within 30 days of the alert. Rates of fall, fracture, or other injury and cognitive impairment were measured during 180-day follow-up. RESULTS: A total of 2704 patients were included: 1373 (50.8%) and 1331 (49.2%) in the dispensed and nondispensed groups, respectively. The dispensed group had a lower unadjusted rate of fall/fracture/injury (3.4% vs 5.3%, p = 0.019), but this difference was attenuated with multivariable adjustment (adjusted odds ratio = 0.77, 95% confidence interval = 0.51-1.13). There was no difference in the rate of cognitive impairment between groups (4.6% vs 4.4%, adjusted odds ratio = 1.40, 95% confidence interval = 0.95-2.05). CONCLUSION: No association was identified between PIM dispensing after a prescriber was alerted with a BPA and reduced rates of falls/fractures/injuries and cognitive impairment.

Birth outcomes with prescribed chronic and acute opioid exposure during pregnancy.

OBJECTIVES: To assess the effects of no, any, and acute and chronic prescription opioid exposure for pain during pregnancy on maternal and fetal outcomes. DESIGN: Retrospective cohort study. SETTING: Integrated healthcare delivery system. Information on pregnancies and their outcomes were obtained from administrative data and verified via manual chart review. PARTICIPANTS: Women ≥ 18 years of age who were pregnant between January 1, 2012 and May 31, 2015 and had chronic, acute, and no opioid exposure; defined as an ambulatory dispensing(s) of >30 (with a total of 225 morphine equivalents), 1-29, and 0 days supply of opioid, respectively, during pregnancy. MAIN OUTCOME MEASURE: Non-live birth. RESULTS: A total 13,809 pregnancies for 13,131 women were included. Pregnancies with opioid exposure had higher risk scores and more comorbid conditions. A total of 1,319 (9.6 percent) pregnancies had any documented opioid exposure during pregnancy with 125 (1.0 percent) and 1,194 (8.7 percent) pregnancies having had chronic and acute opioid exposure, respectively. Pregnancies with acute opioid exposure had a higher percentage of non-live births (3.1 percent) compared to pregnancies (1.0 percent) with no opioid exposure (adjusted odds ratio = 3.46, 95% confidence interval 2.33-5.14) but no difference compared to pregnancies with chronic (1.6 percent) opioid exposure (p > 0.05 with adjustment). CONCLUSIONS: While a dose response of opioid exposure was not identified, these results add to existing evidence that opioid exposure during pregnancy is correlated with negative outcomes. Practitioners may better serve pregnant women and their fetuses by encouraging alternate pain relief treatments.

Trends in high intensity statin use among secondary prevention patients 76 years and older.

BACKGROUND: High intensity statin therapy (HIST) is the gold standard therapy for decreasing the risk of recurrent atherosclerotic cardiovascular disease (ASCVD); however, little is known about the use of HIST in older adults with ASCVD. OBJECTIVES: The aim of this cross-sequential study was to determine trends in statin intensity in older adults over a 10-year timeframe. METHODS: The study was conducted in an integrated healthcare delivery system. Patients were 76 years or older with validated coronary ASCVD. Data were collected from administrative databases. Statin intensity level was assessed in eligible patients on January 1st and July 1st from January 1, 2007 to December 31, 2016. RESULTS: Overall, a total of 5,453 patients were included with 2,119 (38.9%) and 3,334 (61.1%) categorized as HIST and Non-HIST, respectively. Included patients had a mean age of 79.8 years and were primarily male and white and had a cardiac intervention. The rate of HIST use increased from 14.5% to 41.3% over the study period (p<0.001 for trend). Conversely, the rates of moderate and low intensity statin use decreased from 61.8% and 9.8% to 41.2% and 4.8%, respectively (both p<0.001 for trend). Similar trends were identified for females and males. CONCLUSIONS: The percentage of patients with ASCVD 76 years and older who received HIST substantially increased from 2007 to 2016. This trend was identified in both females and males. Future comparative effectiveness research should be conducted in this patient population to examine cardiac-related outcomes with HIST and Non-HIST use.

Clinical Pharmacist Intervention to Engage Older Adults in Reducing Use of Alprazolam.

OBJECTIVE: To assess whether a letter explaining the risks of alprazolam can engage older adults to call a clinical pharmacist (CP) to initiate reduction in alprazolam use. DESIGN: Randomized, controlled study. SETTING: Integrated health care delivery system. PATIENTS: Patients 65 years of age and older who resided at home, had a current supply of alprazolam as of December 15, 2016, and had four outpatient dispensings of alprazolam during the previous 12 months. INTERVENTION: Patients were randomized to receive an educational outreach regarding alprazolam use reduction via a mailed letter (intervention group) or receive usual care (control group). Intervention patients/caregivers were requested to call the CP to discuss reduction of alprazolam use. For intervention patients who called and consented to participate, alternative treatment options were discussed on a case-by-case basis. MAIN OUTCOME MEASURES: Composite rate of 1) no alprazolam dispensing, 2) an alprazolam dose reduction, or 3) interchange to an alternative medication during the six-month follow-up. RESULTS: 153 and 173 patients were and were not, respectively, sent a letter. The mean age was 73 years and patients primarily were female. Thirty (19.6%) intervention patients called the CP. The composite rate was equivalent between the intervention (34.0%) and control (35.3%) groups (P = 0.822). In subanalyses, the composite rate was higher among intervention patients who did vs. those who did not call the CP (77.8% vs. 27.6%; P < 0.001). CONCLUSION: A low-cost patient educational outreach coupled with CP care efficiently engaged older adults in benzodiazepine use reduction process; however, alprazolam continues to be a challenging medication for patients to discontinue.

Pharmacy Technician Management of Stable, In-Range INRs Within a Clinical Pharmacy Anticoagulation Service.

BACKGROUND: There is increasing demand on pharmacist time within clinical pharmacy services, and pharmacy technicians are a crucial resource for expanding pharmacy practice. OBJECTIVE: To assess the safety and effectiveness of pharmacy technician management of stable, in-range international normalized ratio (INR) results compared with usual care. METHODS: This retrospective, longitudinal, noninferiority cohort study was conducted at an integrated health care delivery system with a centralized anticoagulation service. Adult patients receiving chronic warfarin therapy with therapeutic INR results over a 3-month period (i.e., 100% time in therapeutic range [TTR] during the 3 months before the index date) were eligible for referral to technician warfarin management between March 1, 2015, and December 31, 2015. Patients with similar INR control during the same period but not referred to technician management were included as comparators in the usual care group. A one-sided noninferiority margin for the technician management group was set to -2.5% for mean TTR. Propensity scoring was used in regression modeling via inverse probability of treatment weights to compare between-group differences to account for covariates that may have influenced assignment to the technician group. Finally, bleeding, thromboembolic, and mortality outcomes were compared. RESULTS: 1,840 and 1,116 patients were included in the technician and usual care groups, respectively. The mean age of included patients was 73.1 years, and the majority (77.9%) had received warfarin for > 3 years. TTR during follow-up was 83.3% and 77.7% in the technician and usual care groups, respectively (mean difference = 5.7%; 95% CI = 4.1%-7.2%). The risk of thromboembolism was similar between the technician and usual care groups (HR = 0.84; 95% CI = 0.17-4.22; P = 0.832); however, bleeding (HR = 0.60; 95% CI = 0.39-0.94; P = 0.026) and all-cause mortality (HR = 0.44; 95% CI = 0.25-0.77; P = 0.004) were lower in the technician group during follow-up. CONCLUSIONS: Technician management of stable patients receiving chronic warfarin therapy within an integrated health care delivery system's centralized anticoagulation service was associated with noninferior TTR results compared with usual care pharmacist management. DISCLOSURES: This study was internally funded by the Kaiser Permanente Pharmacy Department. The study sponsor had no role in the study design, analysis, or interpretation. The authors have no relevant financial conflicts of interest to disclose.

A Predictive Model to Identify Skilled Nursing Facility Residents for Pharmacist Intervention.

Objective Develop a predictive model to identify patients in a skilled nursing facility (SNF) who require a clinical pharmacist intervention. Design Retrospective, cross-sectional. Setting Nine freestanding SNFs within an integrated health care delivery system. Patients Patients who received a clinical pharmacist medication review between January 1, 2016, and April 30, 2017. Identified patients (n = 2,594) were randomly assigned to derivation and validation cohorts. Interventions Multivariable logistic regression modeling was performed to identify factors predictive of patients who required an intervention (i.e., medication dose adjustment, initiation, or discontinuation). Patient-specific factors (e.g., demographics, medication dispensings, diagnoses) were collected from administrative databases. A parsimonious model based on clinical judgment and statistical assessment was developed in the derivation cohort and assessed for fit in the validation cohort. Main Outcome Measures Model to predict patients requiring clinical pharmacist intervention. Secondary outcome was a comparison of factors between patients who did and did not receive a clinical pharmacist intervention. Results Ninety-five factors were assessed. The derivation (n = 1,299) model comprised 22 factors (area under the curve [AUC] = 0.79, 95% confidence interval [CI] 0.74-0.84). A clopidogrel dispensing (odds ratio [OR] = 2.42, 95% CI 1.19-4.91), fall (OR = 2.47, 95% CI 1.59-3.83), or diagnosis for vertebral fracture (OR = 2.33, 95% CI 1.34-4.05) in the 180 days prior to clinical pharmacist medication review were predictive of requiring an intervention. The model fit the validation cohort (n = 1,295) well, AUC = 0.79 (95% CI 0.74-0.84). Conclusion Administrative data predicted patients in a SNF who required clinical pharmacist intervention. Application of this model in real-time could result in clinical pharmacist time-savings and improved pharmacy services through more directed patient care.

Effect of increased time in the therapeutic range on atrial fibrillation outcomes within a centralized anticoagulation service.

BACKGROUND: Clinical pharmacy anticoagulation services have improved the quality of anticoagulant therapy and are associated with lower rates of bleeding and thromboembolism compared to usual care. Several studies have found that higher time-in-therapeutic range (TTR) during warfarin therapy is associated with better warfarin outcomes. However, whether increasing TTR over time within an established anticoagulation service is associated with further reduction in bleeding and thromboembolic outcomes is unknown. METHODS: This was a retrospective cohort study of patients with atrial fibrillation conducted at an integrated healthcare delivery system with a centralized, pharmacist-managed anticoagulation service. Clinical outcomes (clinically-relevant bleeding, ischemic stroke or systemic embolism, and all-cause mortality) and TTR were compared between two distinct time periods: 1/1/2006 through 12/31/2007 (control group) and 1/1/2012 through 12/31/2013 (observation group) with regression modeling to adjustment for potential confounders. RESULTS: There were 3641 and 4764 patients in the control and observation groups, respectively. The mean age was 74.3 years and 54.4% of the cohort was female. Mean TTR was higher in the observation group (70.5% vs. 63.4%, p < 0.001). The composite outcome of clinically-relevant bleeding, thromboembolism and all-cause mortality occurred in 4.6% and 3.6% of the control and observation groups, respectively (adjusted odds ratio = 0.69; 95% confidence interval 0.54-0.87). Individual rates of stroke/systemic embolism and all-cause mortality were each lower in the observation group (both p < 0.05) while clinically-relevant bleeding was not significantly different (p = 0.256). CONCLUSION: Increased TTR within a clinical pharmacy anticoagulation management service was associated with a lower risk of the composite outcomes of bleeding, thromboembolism and death in a large atrial fibrillation population receiving warfarin.