Prescription of high-risk medications among patients with chronic kidney disease: a cross-sectional study from the Washington, Wyoming, Alaska, Montana and Idaho region Practice and Research Network.

Background: Patients with chronic kidney disease (CKD) are at high risk for adverse drug events related to medication dosing errors and prescriptions for relatively contraindicated medications, such as non-steroidal anti-inflammatory drugs (NSAIDs). Objectives: To examine the scope of and variation in prescribing relatively contraindicated medications and medications above the recommended dose levels among patients with stage III/IV CKD in primary care practice. Methods: This is a cross-sectional descriptive study that used structured electronic health record data. The study participants were patients aged 18 years and older from three primary care clinics in a practice-based research network. Number/proportion of adult patients with stage III/IV CKD; proportion of these patients with at least one NSAID or other relatively contraindicated medication prescribed over 2 years. Results: Of the 7586 eligible adult patients, 4.9% had stage III/IV CKD; 46.6% of these 373 patients with stage III/IV CKD were prescribed at least one relatively contraindicated drug (acarbose, chlorpropamide, glyburide, nitrofurantoin or any NSAID) during the 2-year study period; and 34.0% of patients with stage III/IV CKD were prescribed NSAIDs. Conclusions: Primary care patients with stage III/IV CKD were frequently prescribed or had documented use of relatively contraindicated drugs and thus were at risk of adverse drug events. Given the significant number of individuals with CKD in the USA, research that examines rates of adverse events related to these prescriptions and that tests primary care-based interventions to decrease inappropriate prescribing of relatively contraindicated medications to these patients is needed.

Comparative Effectiveness and Resource Usage in Patients Receiving First-line Taxane-based Chemotherapy for Stage IV Non-Small-cell Lung Cancer in a US Community Oncology Setting.

BACKGROUND: Weekly (qw) nanoparticle albumin-bound (nab)-paclitaxel was approved for advanced non-small-cell lung cancer based on the results from a phase III trial in which nab-paclitaxel/carboplatin demonstrated a significantly greater response rate compared with paclitaxel/carboplatin every 3 weeks (q3w). Little information exists on relative real-world results. MATERIALS AND METHODS: The present retrospective study used data from a national electronic medical record database. Patients receiving first-line nab-paclitaxel qw, paclitaxel qw, or paclitaxel q3w for stage IV non-small-cell lung cancer (NSCLC) were identified. The total cumulative dose, time to treatment discontinuation (TTD), and database persistence (a proxy measure for survival) were analyzed for all patients and for the squamous and elderly subgroups. RESULTS: A total of 114, 208, and 153 patients received nab-paclitaxel qw, paclitaxel qw, and paclitaxel q3w, respectively. In the corresponding treatment arms, the median age was 72, 69, and 67 years; 56%, 48%, and 37% were aged ≥ 70 years; and 75%, 43%, and 23% had squamous cell NSCLC. The total cumulative dose was significantly greater with nab-paclitaxel qw. The TTD was longer with nab-paclitaxel qw than with paclitaxel qw (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.40-0.72; P < .001) or with paclitaxel q3w (HR, 0.53; 95% CI, 0.38-0.73; P < .001). Database persistence was longer with nab-paclitaxel qw than with paclitaxel qw (HR, 0.56; 95% CI, 0.39-0.79; P = .001) or with paclitaxel q3w (HR, 0.52; 95% CI, 0.34-0.78; P = .002). The TTD after experiencing any hematologic adverse event was longer with nab-paclitaxel qw. The findings were consistent across the subgroup analyses. CONCLUSION: In a real-world setting, nab-paclitaxel qw was associated with a significantly greater cumulative dose and significantly longer TTD and database persistence compared with paclitaxel qw and paclitaxel q3w.

Spatial and Census Data to Evaluate Obese Persons and their Environment (SCOPE).

OBJECTIVE: To evaluate the built environment and its relationship to BMI for individuals in eastern Idaho. METHODS: Geospatial analyses were coupled to demographic data of adult individuals. ArcGIS Community Analyst was used to compare demographics relative to median BMI. RESULTS: For every kilometer increase in distance to prepared food sites, BMI went down by 1.3% and every kilometer increase in distance to green space, BMI went down by 0.8% (p < .001). For every kilometer increase in distance to trails, BMI went up by 1.5%. No other built environment variables had a statistically significant association with BMI. CONCLUSION: The distance to prepared foods and trails was associated with expected changes in BMI. Conversely, increased distance to green space was associated with a lower BMI.

Paradoxical reduction in HDL-C with fenofibrate and thiazolidinedione therapy in type 2 diabetes: the ACCORD Lipid Trial.

OBJECTIVE: To determine the occurrence of extremely low HDL cholesterol (HDL-C) among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Trial and to examine the relationship of this finding with treatment with fenofibrate and thiazolidinedione (TZD). RESEARCH DESIGN AND METHODS: The ACCORD Lipid Trial was a randomized, double-blind, placebo-controlled study conducted in patients with type 2 diabetes at 77 clinical centers across the U.S. and Canada in a 5,518-patient subset of the larger 10,251 ACCORD Glycemia Trial. Patients were enrolled from 11 January 2001 to 29 October 2005 and followed until the end of study visits between 1 March and 30 June 2009. Follow-up in the ACCORD Lipid Trial was 4-8 years (mean 4.7 years). Patients were treated with blinded fenofibrate or placebo on a background of simvastatin therapy. The main outcome measures for these descriptive, post hoc analyses was the occurrence of extremely low HDL-C (defined as <25 mg/dL [0.647 mmol/L]) during the trial. RESULTS: Among ACCORD Lipid Trial participants, the occurrence of extremely low HDL-C ever during study follow-up was 106% higher among those randomized to fenofibrate (10.1% fenofibrate vs. 4.9% placebo, P < 0.001). The occurrence of low HDL-C was associated with concurrent treatment with fenofibrate and TZD (7.0% for both vs. 2.2% for neither at 48 months postrandomization). CONCLUSIONS: Idiosyncratic and marked reduction in HDL-C can occur in some patients treated with both fenofibrate and TZD. Practitioners should recognize this important potential idiosyncratic reaction and take appropriate corrective action.

Barriers and facilitators to evidence-based blood pressure control in community practice.

INTRODUCTION: The Electronic Communications and Home Blood Pressure Monitoring trial (e-BP) demonstrated that team care incorporating a pharmacist to manage hypertension using secure E-mail with patients resulted in almost twice the rate of blood pressure (BP) control compared with usual care. To translate e-BP into community practices, we sought to identify contextual barriers and facilitators to implementation. METHODS: Interviews were conducted with medical providers, staff, pharmacists, and patients associated with community-based primary care clinics whose physician leaders had expressed interest in implementing e-BP. Transcripts were analyzed using qualitative template analysis, incorporating codes derived from the Consolidated Framework for Implementation Research (CFIR). RESULTS: Barriers included incorporating an unfamiliar pharmacist into the health care team, lack of information technology resources, and provider resistance to using a single BP management protocol. Facilitators included the intervention's perceived potential to improve quality of care, empower patients, and save staff time. Sustainability of the intervention emerged as an overarching theme. CONCLUSION: A qualitative approach to planning for translation is recommended to gain an understanding of contexts and to collaborate to adapt interventions through iterative, bidirectional information gathering. Interviewees affirmed that web pharmacist care offers small primary care practices a means to expand their workforce and provide patient-centered care. Reproducing e-BP in these practices will be challenging, but our interviewees expressed eagerness to try and were optimistic that a tailored intervention could succeed.

Contraceptive methods and informed consent among women receiving medications with potential for adverse fetal effects: a Washington, Wyoming, Alaska, Montana, Idaho (WWAMI) region study.

BACKGROUND: Increasing diabetes, hypertension, and hypercholesterolemia rates expose some young women to medications with potential adverse fetal effects, such as angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and statins. This study examined whether quality improvement (QI) interventions promote informed consent and contraception to minimize risks with use of ACE-I/ARB/statins. METHODS: This longitudinal cohort study at 7 clinics abstracted medical records of 328 women aged 18 to 44 with ≥1 prescription for ACE-I/ARB/statins and ≥1 visit for hypertension, diabetes, or hypercholesterolemia during the previous year. We measured informed consent documentation and contraceptive methods before and after QI interventions in which providers contacted their patients to discuss medication risks and benefits. RESULTS: Of 179 women who were not surgically sterilized, only 11.7% had documented informed consent related to the risks of ACE-I/ARB/statin use. One hundred fifty-eight women were eligible for the QI intervention (not surgically sterilized, no documented informed consent); only 76 (48.1%) received the intervention. Before the intervention, 23.7% of these 76 were "at risk" of an adverse fetal effect. After the intervention, only 7.9% (P ≤ .001) were "at risk" because some women started contraception, discontinued ACE-I/ARB/statins, or changed drug class. CONCLUSIONS: Women prescribed ACE-I/ARB/statins were not consistently using contraception or were not consistently informed of the risks. Provider-implemented QI interventions improved care but were difficult to accomplish, suggesting that new interventions are needed.

Developing a practice-based research network by integrating quality improvement: challenges and ingredients for success.

Improving patient outcomes in community-based settings is the goal of both the Clinical Translational Science Award program and practice-based quality improvement (QI) programs. Given this common goal, integrating QI and outcomes research is a promising strategy for developing, implementing, and evaluating clinical interventions. This article describes the challenges and strengths illuminated by the conduct of a combined research/QI study in a nascent practice-based research network. Challenges include research's exclusion of clinic patients who might benefit from the intervention; QI programs' less uniform approach to intervention implementation; and the need for both academic and clinically relevant products and publications. A major strength is the increased likelihood of both engaging clinical practices in research and developing successful clinical interventions. Required elements for success include identification of enthusiastic clinical research "champions," involvement of researchers with clinical experience, and adequate funding to support both research and clinical resources and dissemination. Combined Ql/research projects in the practice-based research environment have the potential to improve and shorten the cycle from good idea to improved clinical outcomes in real-world settings.

Variation in refill protocols and procedures in a family medicine residency network.

BACKGROUND AND OBJECTIVES: Efficient and accurate medication refill authorization is an integral service provided by family physicians and an essential skill to teach family medicine residents. The goal of this study was to examine the variation in medication refill protocols, procedures, and resources in family medicine residency practices across a five-state region as a background for development of best practices. METHODS: Structured telephone interviews with a key informant at each of 11 clinical practices in a five-state (Washington, Wyoming, Alaska, Montana, and Idaho) family medicine residency network focused on refill protocols and procedures, which personnel have authorization authority, and other factors related to refill protocols and medication prescribing curriculum. Key themes were abstracted from interview notes. RESULTS: There was marked variation in refill protocols and procedures across the clinical sites. While all practices were able to identify their refill procedure, no two practices' procedures were the same, and only 36.4% had a formal written protocol that could be identified by the key informant. All of the practices with formal protocols routinely reviewed medical records before authorizing refills (100%, four/four) compared to less than half of those without formal protocols (42.9%, three/seven). Practices with formal protocols (75.0%) also transferred refill requests between staff prior to authorization more than those without formal protocols (57.1%). CONCLUSIONS: Refill protocols and procedures were highly variable across these family medicine residency program practices. Surprisingly, formal written refill protocols were uncommon. Further research to identify best practices in medication refill procedures associated with safety outcomes is warranted.

Intensive glycemic control is not associated with fractures or falls in the ACCORD randomized trial.

OBJECTIVE: Older adults with type 2 diabetes are at high risk of fractures and falls, but the effect of glycemic control on these outcomes is unknown. To determine the effect of intensive versus standard glycemic control, we assessed fractures and falls as outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) randomized trial. RESEARCH DESIGN AND METHODS: ACCORD participants were randomized to intensive or standard glycemia strategies, with an achieved median A1C of 6.4 and 7.5%, respectively. In the ACCORD BONE ancillary study, fractures were assessed at 54 of the 77 ACCORD clinical sites that included 7,287 of the 10,251 ACCORD participants. At annual visits, 6,782 participants were asked about falls in the previous year. RESULTS: During an average follow-up of 3.8 (SD 1.3) years, 198 of 3,655 participants in the intensive glycemia and 189 of 3,632 participants in the standard glycemia group experienced at least one nonspine fracture. The average rate of first nonspine fracture was 13.9 and 13.3 per 1,000 person-years in the intensive and standard groups, respectively (hazard ratio 1.04 [95% CI 0.86-1.27]). During an average follow-up of 2.0 years, 1,122 of 3,364 intensive- and 1,133 of 3,418 standard-therapy participants reported at least one fall. The average rate of falls was 60.8 and 55.3 per 100 person-years in the intensive and standard glycemia groups, respectively (1.10 [0.84-1.43]). CONCLUSIONS: Compared with standard glycemia, intensive glycemia did not increase or decrease fracture or fall risk in ACCORD.

Comparing medical cost of care for patients with metastatic breast cancer receiving taxane therapy: claims analysis.

BACKGROUND: It has been estimated that more than $8 billion is spent annually on the management of breast cancer in the United States. The taxane chemotherapeutic agents are cornerstones in the treatment of breast cancer, yet no study has assessed whether the choice of a taxane affects the economic outcomes of metastatic breast cancer treatment. OBJECTIVE: To determine if differences exist in the medical cost of care in patients receiving taxane-based chemotherapy for metastatic breast cancer, and to compare the use of ancillary medications (for neutropenia, anemia, and nausea and vomiting) and their associated costs among taxanes. METHOD: We identified women with metastatic breast cancer based on diagnosis codes and the women's previous adjuvant chemotherapeutic regimens. Paid medical insurance claims were captured for the 24-month study period, from January 1, 2006, through December 31, 2007. The groups were determined according to the specific taxane administered. Total medical costs were captured from the date of first taxane administration to the end of data availability. Outpatient pharmacy costs were not available. A multivariate analysis was used to evaluate the total medical costs in each group. Median total medical costs per patient per month during the study period were adjusted using a multiple regression analysis. Utilization and cost of medications administered in the office or hospital for chemotherapy-induced adverse effects were captured and adjusted with Tobit models. RESULTS: Of the 2245 study participants, 1035 received docetaxel, 997 received generic paclitaxel, and 213 received nab-paclitaxel. On average, patients in the nab-paclitaxel group received more doses (9.6) than those in the generic paclitaxel (6.0) or docetaxel (4.8) groups. The multivariate analysis was robust, explaining 72% of the variability in total medical costs across the 3 taxane groups. Median per-patient per-month total medical costs for study participants were within approximately $800 of each other among the groups. Generic paclitaxel had the lowest total medical costs. The total costs for docetaxel and nab-paclitaxel were not significantly different. Nab-paclitaxel had the lowest utilization and lowest costs associated with colony-stimulating factors. The proportion of patients receiving erythropoiesis-stimulating agents was not significantly different among the 3 drugs, but the costs for these agents were significantly lower in patients receiving nab-paclitaxel than in those receiving docetaxel. Antiemetic use was highest in the docetaxel group, but the costs for antiemetics were not different among the 3 taxane groups. CONCLUSION: The differences in total medical costs among the 3 taxanes were modest. Total medical costs were lowest for patients receiving generic paclitaxel and comparable between the docetaxel and nab-paclitaxel groups. Patients taking nab-paclitaxel received more doses than patients taking the other taxanes. Nab-paclitaxel was associated with lower utilization and costs for colony-stimulating factors compared with generic paclitaxel and docetaxel.

Abuse potential of carisoprodol: a retrospective review of Idaho Medicaid pharmacy and medical claims data.

BACKGROUND: Carisoprodol is a muscle relaxant indicated as adjunctive therapy in acute, painful musculoskeletal conditions. Case reports of drug-seeking behavior and utilization of carisoprodol in combination with opioids have suggested abuse potential. OBJECTIVES: We undertook a retrospective review of claims data to identify and characterize potential indicators of abuse in long-term users of carisoprodol and to determine any continued use of the drug by former long-term users following prior authorization implementation. METHODS: The Idaho Medicaid pharmacy and medical claims database was queried from January 1 to December 31, 2005, to identify long-term users of muscle relaxants. Use of concomitant opioids and coded diagnoses relating to past drug abuse were analyzed and compared between patients who used carisoprodol and patients who used other muscle relaxants. Data from 11 of 30 surveys mailed to pharmacies filling prescriptions for long-term users of carisoprodol were also collected to determine the frequency of self-pay-continued use after Medicaid coverage of the drug was discontinued. RESULTS: Long-term users of carisoprodol (n = 340) and other skeletal muscle relaxants (SMRs) (n = 453) were identified from among 130,000 individuals in the Idaho Medicaid pharmacy and medical claims database in calendar year 2005. Patients in both groups were similar in terms of mean age (~47 years) and sex (71.5% female). Patients using carisoprodol used concomitant opioids more frequently (81.5% vs 59.8%; P < 0.01), more commonly had past diagnoses indicating other drug abuse (34.1% vs 21.4%; P < 0.01), and in 80% of reported cases, continued to pay out of pocket for carisoprodol when third-party coverage was discontinued. Taken together, these findings are consistent with published case reports suggesting the abuse potential of carisoprodol. CONCLUSIONS: The results from this review suggest that, compared with long-term users of other SMRs, carisoprodol patients utilized concomitant opioids more frequently and concomitant NSAIDs less frequently, more commonly had past diagnoses indicating other drug dependence or abuse, and continued to pay out of pocket for carisoprodol when third-party coverage was discontinued. While none of these issues alone may be direct indicators of abuse, collectively they suggest that patients who used carisoprodol long term displayed abuse potential characteristics more frequently than long-term users of other agents.

Impact of safety warnings on drug utilization: marketplace life span of cisapride and troglitazone.

STUDY OBJECTIVE: To evaluate the impact of safety alerts on the volume of cisapride and troglitazone usage. DESIGN: Retrospective database analysis. SETTING: University research center. MATERIAL: Idaho Medicaid claims data from January 1994--July 2000. MEASUREMENTS AND MAIN RESULTS: Monthly counts of total and new prescriptions filled for cisapride and troglitazone were analyzed graphically over time as a function of all prescriptions. New prescriptions were defined as those filled by patients who had not received the drug within the previous year. A binomial comparison of the 5 months before and after each safety alert was conducted by Poisson distribution. Overall and new cisapride usage increased after the first alert, which occurred in February 1995 (p<0.05). After the second alert, in September 1995, growth in new prescriptions ended but total prescriptions continued to grow (p<0.05). After the third alert, in June 1998, growth in total use ended and the number of new prescriptions declined (p<0.05). The final two alerts (June 1999 and January 2000) were met with significant declines (p<0.05 for both). Troglitazone was the subject of two alerts in October and December 1997. After these, overall usage increased (p<0.05), whereas the number o new prescriptions decreased (p<0.05). The third alert, in July 1998, caused no change as total prescription use continued to grow (p<0.05), whereas the number of new prescriptions decreased (p<0.05). A fourth alert, in June 1999, resulted in a decrease of overall usage and new prescriptions (p<0.05 for both). CONCLUSION: Numerous safety alerts were required for each drug before drug usage declined. The decline in overall use was slower than the decline in new prescriptions, possibly indicating a need for increased assessment of refilled prescriptions after the release of new safety data.

Cardiovascular outcomes using doxazosin vs. chlorthalidone for the treatment of hypertension in older adults with and without glucose disorders: a report from the ALLHAT study.

Insulin resistance underlies most glucose disorders in adults and is associated with an increased risk of cardiovascular disease. Alpha blockers decrease insulin resistance, whereas diuretics increase insulin resistance. The authors studied the effects of these two classes of hypertension medications (doxazosin, an a blocker, and chlorthalidone, a diuretic) on cardiovascular disease outcomes in adults aged >55 years with hypertension and glucose disorders who were participants in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (8749 had known diabetes mellitus and 1690 had a newly diagnosed glucose disorder [fasting glucose >/=110 mg/dL]). There was no difference in either group between the chlorthalidone- and doxazosin-based treatments with regard to fatal or nonfatal myocardial infarction or all-cause mortality. There was, however, a difference for combined cardiovascular disease (myocardial infarction, revascularization procedures, angina, stroke, heart failure, and peripheral arterial disease) in favor of the diuretic. This difference was due primarily to an increased heart failure risk in those treated with doxazosin (relative risk, 1.85; 95% confidence interval, 1.56-2.19) in the known diabetes mellitus group and a relative risk of 1.63 (95% confidence interval, 1.05-2.55) in those with a newly diagnosed glucose disorder despite lower glucose levels on follow-up in those treated with a blockers. The authors conclude that treatment of hypertension with doxazosin in adults with glucose disorders incurs the same risk of coronary heart disease as treatment with chlorthalidone; however, treatment with doxazosin increases the risk of combined cardiovascular disease and heart failure despite lower glucose levels.

Evidence-based medicine and information mastery: application for acute gastrointestinal conditions.

Although advances in medical therapeutics are providing more options to improve patient care, the medical professional, wading through information overload, may not be effective in critically evaluating new data and making informed decisions based on them. Evidence-based medicine and information mastery offer clear guidelines to help health care professionals critically evaluate the relevance and validity of articles as they relate to patient care. When evaluating literature it is important to emphasize patient-oriented evidence that matters, rather than disease-oriented evidence.

Ambulatory care increased vitamin B12 requirement associated with chronic acid suppression therapy.

BACKGROUND: Assimilation of vitamin B(12) from dietary sources requires gastric acid. By decreasing acid production, the proton pump inhibitors (PPIs) and histamine(2) (H(2))-blockers may reduce vitamin B(12) absorption. OBJECTIVE: To determine whether chronic acid suppression therapy is associated with the initiation of vitamin B(12) supplementation, we conducted a retrospective case-control study using a state-wide Medicaid population. METHODS: Case patients were identified as those who initiated vitamin B(12) supplementation during the study period. Four control patients were age- and gender-matched to each case. Patients (n = 109 844) with a paid claim between September 27, 1995, and September 27, 1997, were eligible for inclusion. Chronic acid suppression therapy was defined as treatment with H(2)-blockers or PPIs for >/=10 of the 12 months prior to the first vitamin B(12) injection. Comparisons were made between the case and control groups regarding exposure to chronic acid suppression therapy. RESULTS: One hundred twenty-five cases were matched to 500 controls. Twenty-three patients (18.4%) had been exposed to chronic acid suppression therapy compared with 55 (11.0%) of the control group (p = 0.025; OR 1.82; 95% CI 1.08 to 3.09). CONCLUSIONS: Initiation of vitamin B(12) supplementation was associated with chronic gastric acid suppression therapy.

Erythropoietin-induced hypertensive urgency in a patient with chronic renal insufficiency: case report and review of the literature.

Hypertension is a potentially dangerous side effect of erythropoietin treatment; however, extreme elevations in blood pressure are rare. A 75-year-old woman with chronic renal insufficiency was treated with subcutaneous erythropoietin. Three weeks before she started receiving erythropoietin, her hematocrit was 27.2%; after 5 weeks of treatment, it rose to 45.7%. The patient came to the emergency department and was admitted with hypertensive urgency. During her hospital stay she was treated with nitroglycerin and nitroprusside infusions, extended-release nifedipine, a variety of beta-blockers, clonidine, and furosemide. By day 3, her blood pressure was adequately controlled. Her renal insufficiency may have progressed as a result of the hypertensive episode, which probably was related to erythropoietin administration and the resultant rapid increase in her hematocrit. Erythropoietin dosing should be titrated to increase the hematocrit gradually, and blood pressure should be monitored closely to avoid serious side effects such as hypertensive emergencies.

Detriments of tPA for acute stroke in routine clinical practice.

Under optimal conditions, tissue plasminogen activator (tPA) may be a viable option for treatment of acute ischemic stroke; however, this study showed that protocol is not adhered to in practice and that these protocol deviations are associated with increased mortality and other adverse events. Based on these findings, tPA should not be used in routine clinical practice to treat acute stroke until individual hospitals develop protocols to guarantee the medication's appropriate use.