Effect of pregabalin initiation on diuretic requirements in patients with chronic heart failure.

BACKGROUND: Literature on pregabalin use in patients with heart failure is largely limited to patient case reports and cohort studies. OBJECTIVE: This study aimed to evaluate the effect of pregabalin initiation on diuretic requirements in patients with heart failure. METHODS: A retrospective analysis of patients with heart failure who were started on pregabalin between January 1, 2014, and September 1, 2021, at the Veterans Affairs North Texas Health Care System was used. The primary objective was to determine the median change in loop diuretic dose, in furosemide dose equivalents, 6 months after pregabalin initiation. RESULTS: Of 58 patients analyzed, there was no statistically significant difference in the primary outcome (P = 0.162). The secondary outcomes were found to be nonstatistically significant, and there was no correlation between pregabalin dose and outcomes. CONCLUSION: This represents the largest analysis of diuretic dose requirements in patients with heart failure after initiation of pregabalin. Although there was no difference in the median change of diuretic dose prescribed, pregabalin should still be used with caution.

We'll take it from here: Veterans Affairs OPAT management of home IV therapy initiated at community hospitals.

An outpatient parenteral antimicrobial therapy team from a Veterans Affairs facility managed patients discharged from their own facility and neighboring community hospitals. There were no significant differences in adverse outcomes between the groups, but a majority of regimens were modified from those initially proposed by community providers.

Provider Decisions and Patient Outcomes After Premature Metformin Discontinuation.

The purpose of this study was to evaluate the effects of alternative antihyperglycemic therapy after discontinuation of metformin due to documented declining renal function. This retrospective, single-site study evaluated patients who had metformin discontinued between 1 January 1999 and 30 September 2013. Medical records were evaluated for documented adverse events, subsequent glycemic control, and costs associated with the alternative therapy. Patients served as their own controls. A total of 179 patients met study entry criteria, and their peak A1C was significantly higher within the year after metformin discontinuation (P <0.001). After the provider added new medications to control patients' blood glucose, their A1C by the end of the first year after discontinuing metformin was similar to their A1C while taking metformin. Significant weight gain accompanied the use of the medications added to replace metformin, with an average increase of 3.81 kg (P <0.001). Additionally, after discontinuing metformin, more patients experienced hypoglycemia with the addition of other medications to control their blood glucose (P <0.001). As expected, the cost of therapy was significantly higher (P <0.0001) after metformin was discontinued because metformin was generically available, whereas the replacement medications frequently were not. Providers should consider the expanded recommendations for the use of metformin in patients with mild to moderate stable renal dysfunction to help such patients avoid weight gain, hypoglycemia, loss of blood glucose control, and increased costs.

Anticoagulation Management Outcomes in Veterans: Office vs Telephone Visits.

Patients on anticoagulation therapy who transitioned to telephone visits from office visits showed no change in therapeutic outcomes.

Substantial improvement in prophylactic antibiotic administration for open fracture patients: results of a performance improvement program.

OBJECTIVES: Administration of early and appropriate antibiotic in treating patients with open fractures is an important early factor in preventing infection and optimizing outcomes. The purpose of this study is to evaluate the effects of an orthopaedic trauma performance improvement program directed at early antibiotic administration for open fracture patients at our trauma center. DESIGN: Retrospective comparative cohort study of patients treated for an open fracture by before and after implementation of our performance improvement program specifically designed to address early open fracture care. SETTING: Single metropolitan level 2 regional trauma center. PATIENTS: Patients with open fractures treated by orthopaedic surgery (hand and spine excluded) at our institution between January 2012 and December 2013 were included. Patients transferred from another facility were excluded. INTERVENTION: Patients were divided into one of the following 2 groups. Group 1 included patients treated before our open fracture performance improvement program (January 2012-December 2012) and group 2 comprised those treated after the program was instituted (January 2013-December 2013). MAIN OUTCOME MEASUREMENTS: Patient demographics, injury factors, and performance measures relating to early open fracture care [eg, the characteristics of early antibiotic administration in their treatment course, including timeliness of prophylactic intravenous (IV) antibiotic therapy and reasons for delay or omission of these treatments] were evaluated. RESULTS: Group 1 was comprised of 127 patients with a total of 142 open fractures, whereas group 2 included 132 patients with a total of 156 open fractures. Patient and injury factors were not significantly different between the 2 groups. Group 1 received IV antibiotics at an average of 70.5 minutes after arrival at our institution compared with group 2 who received antibiotics at an average of 32.4 minutes (P < 0.001). The average times from emergency department arrival to physician evaluation improved from 6.5 to 4.5 minutes (P = 0.02) and antibiotic order to antibiotic delivery improved from 37 to 13 minutes (P < 0.001) for group 1 compared with group 2, respectively. The average time between physician evaluation and antibiotic showed a trend toward improvement (12.7-8.0 minutes, P = 0.57). Fifty percent of patients in group 1 (63/127) had antibiotics initiated within 1 hour of hospital arrival, whereas 78% (100/132) in group 2 had antibiotics initiated within 1 hour (P < 0.001). Eighty-five percent (112/127) of patients in group 1 had antibiotics initiated within 3 hours of hospital arrival, whereas 95% (125/132) in group 2 had antibiotics initiated within 3 hours (P = 0.03). Of those patients receiving standard antibiotics (cephalosporin), 79% (85/107) in group 1 and 91% (104/114) in group 2 received the recommended dose of IV antibiotic for their body weight (e.g., 2 g cefazolin for patients of >80 kg) (P < 0.006). CONCLUSIONS: Optimal treatment of open fracture patients with early and appropriate antibiotic prophylaxis was lacking for many patients at our trauma center. A multifaceted performance improvement program specifically concentrating on education, accountability, and antibiotic availability aimed at this aspect of orthopaedic trauma care was very effective in improving our early treatment of these patients. LEVEL OF EVIDENCE: Therapeutic level III. See instructions for authors for a complete description of levels of evidence.

Outcomes of a preoperative "bridging" strategy with glycoprotein IIb/IIIa inhibitors to prevent perioperative stent thrombosis in patients with drug-eluting stents who undergo surgery necessitating interruption of thienopyridine administration.

AIMS: Surgery after drug-eluting stent (DES) implantation may be associated with increased risk for perioperative stent thrombosis (ST). METHODS AND RESULTS: We evaluated the outcomes of 67 patients who underwent non-cardiac (n=51) or cardiac (n=16) surgery after DES implantation at our institution between 2008 and 2010 and who underwent preoperative "bridging" with a glycoprotein IIb/IIIa inhibitor. Surgery occurred after a mean time of 13.9 ± 1.7 and 8.7 ± 2 months post stenting for non-cardiac (NCS) and cardiac surgery, respectively. Glycoprotein IIb/IIIa inhibitors were administered preoperatively for a mean of 7.1 ± 0.4 and 7.8 ± 0.7 days, respectively, then discontinued four to six hours before surgery. Most patients received aspirin through the perioperative period (33 NCS patients and 15 cardiac surgery patients). Clopidogrel was restarted as early as possible in the postoperative period. In the non-cardiac surgery group, two patients (3.9%, 95% confidence intervals 0.5% to 13.5%) suffered acute ST in the immediate postoperative period and four patients suffered major bleeding by the Global Utilisation of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) criteria. One cardiac surgery patient had probable ST one hour postoperatively. CONCLUSIONS: In spite of preoperative "bridging" with a glycoprotein IIb/IIIa inhibitor, postoperative stent thrombosis can still occur in patients with prior DES undergoing surgery requiring antiplatelet medication interruption.

Pilot trial of cryoplasty or conventional balloon post-dilation of nitinol stents for revascularization of peripheral arterial segments: the COBRA trial.

OBJECTIVES: The purpose of this study is to compare post-dilation strategies of nitinol self-expanding stents implanted in the superficial femoral artery of diabetic patients with peripheral arterial disease. BACKGROUND: Endovascular treatment of superficial femoral artery disease with nitinol self-expanding stents is associated with high rates of in-stent restenosis in patients with diabetes mellitus. METHODS: We conducted a prospective, multicenter, randomized, controlled clinical trial of diabetic patients to investigate whether post-dilation of superficial femoral artery nitinol self-expanding stents using a cryoplasty balloon reduces restenosis compared to a conventional balloon. Inclusion criteria included diabetes mellitus, symptomatic peripheral arterial disease, and superficial femoral artery lesions requiring implantation of stents>5 mm in diameter and >60 mm in length. Primary endpoint was binary restenosis at 12 months, defined as ≥2.5-fold increase in peak systolic velocity by duplex ultrasonography. RESULTS: Seventy-four patients, with 90 stented superficial femoral artery lesions, were randomly assigned to post-dilation using cryoplasty (n=45 lesions) or conventional balloons (n=45 lesions). Mean lesion length was 148±98 mm, mean stented length was 190±116 mm, mean stent diameter was 6.1±0.4 mm, and 50% of the lesions were total occlusions. Post-dilation balloon diameters were 5.23±0.51 mm versus 5.51±0.72 mm in the cryoplasty and conventional balloon angioplasty groups, respectively (p=0.02). At 12 months, binary restenosis was significantly lower in the cryoplasty group (29.3% vs. 55.8%, p=0.01; odds ratio: 0.36, 95% confidence interval: 0.15 to 0.89). CONCLUSIONS: Among diabetic patients undergoing implantation of nitinol self-expanding stents in the superficial femoral artery, post-dilation with cryoplasty balloon reduced binary restenosis compared to conventional balloon angioplasty. (Study Comparing Two Methods of Expanding Stents Placed in Legs of Diabetics With Peripheral Vascular Disease [COBRA]; NCT00827853).

The effects of clopidogrel (Plavix) and other oral anticoagulants on early hip fracture surgery.

OBJECTIVE: Risk for bleeding complications during and after early hip fracture surgery for patients taking clopidogrel and other anticoagulants have not been defined. The purpose of this study is to assess the perioperative bleeding risks and clinical outcome after early hip fracture surgery performed on patients taking clopidogrel (Plavix) and other oral anticoagulants. DESIGN: Study design is a retrospective cohort analysis using data extracted from hospital records and state death records. SETTING: Regional medical center (level II trauma). METHODS: Data for 1118 patients ≥60 years of age who had surgical treatment for a hip fracture between 2004 and 2008 were reviewed. Eighty-two patients undergoing late surgery (>3 days after admission) were excluded. Patients taking clopidogrel were compared against those not taking clopidogrel. In addition, patients taking clopidogrel only were compared against cohorts of patients taking both clopidogrel and aspirin, aspirin only, warfarin only, or no anticoagulant. RESULTS: Seventy-four of 1036 patients (7%) were taking clopidogrel, although control groups included 253 patients on aspirin alone, 90 patients on warfarin, and 619 taking no anticoagulants. No significant differences were noted between patients taking clopidogrel and those not taking clopidogrel in estimated blood loss, transfusion requirement, final blood count, hematoma evacuation, hospital length of stay (LOS), or mortality while in hospital or at 1 year. A higher American Society of Anesthesiologists score was seen in the clopidogrel and warfarin groups (P = 0.05 each), increased LOS in the clopidogrel group (P = 0.05), and higher rate of deep vein thrombosis seen in those patients taking warfarin (P = 0.05). Clopidogrel only versus aspirin versus both aspirin and clopidogrel, versus no anticoagulant versus warfarin showed no significant differences in estimated blood loss, transfusion requirement, final blood count, bleeding or perioperative complications, or mortality. CONCLUSIONS: Patients undergoing early hip fracture surgery who are taking clopidogrel, aspirin, or warfarin (with regulated international normalized ratio) are not at substantially increased risk for bleeding, bleeding complications, or mortality. Comorbidities and American Society of Anesthesiologists scores were significantly higher in the clopidogrel group, which may have resulted in the increased postoperative LOS in this group.

U500 regular insulin use in insulin-resistant type 2 diabetic veteran patients.

OBJECTIVE: To evaluate the use of U500 regular insulin therapy in insulin-resistant patients with type 2 diabetes mellitus who were previously treated with high-dosage U100 insulin regimens. METHODS: At a large Veterans Affairs medical center, a retrospective chart review was performed of all patients whose U100 insulin regimens were converted to U500 regular insulin regimens using a protocol to ensure patient safety. Patients were followed up for longer than 6 months. Data reviewed included total daily dosage of insulin before and after regimen conversion and changes in hemoglobin A1c, body weight, lipids, and episodes of severe hypoglycemia. RESULTS: Fifty-three patients met inclusion criteria. Average hemoglobin A1c level on U100 insulin regimens was 9.1 ± 1.7%, which decreased to 8.1 ± 1.3% (P<.001) after an average of 20 months (range, 6-52 months) on U500 insulin. The total daily insulin dosage at study end was not significantly greater on U500 (415 ± 166 units/day) than on U100 insulin (391 ± 120 units/day) (P = .34). Body weight did not change significantly (134 ± 29 kg vs 136 ± 30 kg, P = .18). There was a 20-mg/dL decrease in total cholesterol (P = .014). Triglyceride values decreased by 97 mg/dL (P = .005). Eight episodes of severe hypoglycemia were documented in patients treated with U500 insulin, but this was similar to the incidence in these same patients while treated with U100 insulin. CONCLUSION: We conclude that U500 insulin can be safely and effectively used in insulin-resistant patients with type 2 diabetes followed up at a large Veterans Affairs medical center using a protocol that ensures patients are thoroughly educated and carefully monitored.

Effect of concomitant use of clopidogrel and proton pump inhibitors after percutaneous coronary intervention.

The aim of the present study was to analyze the effect of drug exposure patterns of clopidogrel and proton pump inhibitors (PPIs) on the clinical outcomes after percutaneous coronary intervention (PCI). Previous analyses predominantly included discharge medications and did not explore the effect of the drug exposure patterns. We analyzed all-cause death, nonfatal myocardial infarction, repeat revascularization, and major adverse cardiovascular events (MACE) in a cohort of 23,200 post-PCI patients (January 2003 to December 2008) using a multivariate adjusted Cox model and propensity-matched case-control analysis. The adjusted hazard ratio for MACE on PPI according to the exposure patterns of clopidogrel after PCI for 6 years was 1.24 (95% confidence interval [CI] 1.11 to 1.38) and 1.12 (95% CI 1.03 to 1.22) for "continuous" (consistent clopidogrel with or without PPIs) and "switched" (clopidogrel with or without varying PPIs) respectively. However, the propensity score adjusted odds ratios for MACE on PPI use was 0.97 (95% CI 0.65 to 1.44) for "continuous" and 1.04 (95% CI 0.87 to 1.25) for "switched." Moreover, in the first year after PCI, the use of "rescue" (≤30 days before MACE) nitroglycerin was greater in the patients taking clopidogrel and PPIs than in those taking clopidogrel alone, as was the overall use of rescue PPIs (p <0.001). In conclusion, PPI use in clopidogrel-treated post-PCI patients was not associated with an increased risk of MACE after controlling for the confounding effect of PPI use with propensity matching. A potential for the misdiagnosis of angina symptoms and rescue use of nitroglycerin and PPIs in post-PCI patients exists, a finding that might have confounded previous observational analyses.

Comparison of the impact of short (<1 year) and long-term (> or =1 year) clopidogrel use following percutaneous coronary intervention on mortality.

The optimal duration of clopidogrel administration after percutaneous coronary intervention (PCI) remains unknown. Clopidogrel is currently recommended for minimums of 1 and 12 months after bare-metal stent and drug-eluting stent implantation, respectively. To determine the impact of clopidogrel discontinuation 1 year after PCI, the outcomes of 530 consecutive patients who underwent PCI from January 2004 to July 2006, were free of cardiovascular events for 6 months after PCI, and had follow-up available for >12 months were examined. The outcomes of patients who received clopidogrel for > or =1 year were compared with those of patients who received it for <1 year. The mean age was 65 +/- 9 years. Patients often presented with acute coronary syndromes (57%), and 85% received drug-eluting stents. Clopidogrel was used for > or =1 year and for <1 year in 341 and 189 patients, respectively. During a mean follow-up period of 2.4 +/- 0.8 years, 40 patients (8%) died, 21 (4%) had acute myocardial infarctions, and 89 (17%) underwent repeat coronary revascularization. Compared with patients with clopidogrel administration for <1 year after PCI, those who received clopidogrel for > or =1 year had lower mortality (14.8% vs 3.5%, p <0.001). On multivariate analysis, clopidogrel use for > or =1 year was associated with lower mortality (hazard ratio 0.28, 95% confidence interval 0.14 to 0.59), independent of traditional cardiovascular risk factors, clinical presentation, and the use of drug-eluting stents. In conclusion, the use of clopidogrel for > or =1 year after PCI was associated with lower mortality.

The risk of acute myocardial infarction with etodolac is not increased compared to naproxen: a historical cohort analysis of a generic COX-2 selective inhibitor.

BACKGROUND: This study compares the risk of acute myocardial infarction among patients exposed to etodolac, naproxen, celecoxib, and rofecoxib. METHODS: A retrospective cohort study in 38 258 veteran patients (26 376 patient-years) measured the adjusted odds ratios of acute myocardial infarction during exposure to etodolac, naproxen, celecoxib, or rofecoxib. RESULTS: Diagnosis of acute myocardial infarction was confirmed in 100 patients who were exposed to a study nonsteroidal anti-inflammatory drug. Compared to naproxen, the increased risk of acute myocardial infarction was not significant for etodolac (OR = 1.32, P = .27), whereas celecoxib (OR = 2.18, 95% CI 1.09-4.35, P = .03) and rofecoxib (OR = 2.16, 95 CI 1.04-4.46, P = .04) were significant. A post hoc analysis indicates that patients with a prior history of acute myocardial infarction had a significant, 4.26-fold risk for another acute myocardial infarction if taking celecoxib or rofecoxib. CONCLUSION: Etodolac is not associated with a statistically increased risk of acute myocardial infarction compared to naproxen.

Risks of clinically significant upper gastrointestinal events with etodolac and naproxen: a historical cohort analysis.

BACKGROUND AND AIMS: Etodolac is a generic nonsteroidal anti-inflammatory drug (NSAID). Previous in vitro studies have shown that etodolac is a selective inhibitor of cyclooxygenase (COX)-2 with selectivity in between that of other COX-2 inhibitors such as celecoxib and rofecoxib. However, there are no outcomes data assessing clinically significant upper gastrointestinal (CSUGI) events with etodolac. METHODS: A historical cohort study was performed at the Dallas Veterans Affairs Medical Center in which 16,286 veteran patients (5596 patient-years) received etodolac or naproxen during a 3-year period without concurrent use of other ulcerogenic drugs other than low-dose aspirin. The primary outcome was the CSUGI event rate of the etodolac and naproxen groups without concomitant low-dose aspirin. RESULTS: The incidence of CSUGI events was .78% and .24% for naproxen and etodolac, respectively. In the NSAID-naive subset, the incidence of CSUGI events was .99% and .24% for naproxen and etodolac, respectively. Compared with naproxen, etodolac was associated with a reduction in upper gastrointestinal events, corresponding to an odds ratio of .39 (95% confidence interval, .20-.76; P = .006). Concomitantly used low-dose aspirin increased event rates with naproxen 2-fold and etodolac 9-fold. Hence, there was no significant difference in gastrointestinal event rates between etodolac and naproxen when low-dose aspirin was taken concomitantly. CONCLUSIONS: Etodolac is a generic COX-2 selective inhibitor that reduces CSUGI events compared with the nonselective NSAID naproxen. However, concomitant use of low-dose aspirin negates the gastrointestinal safety advantages of etodolac.

Amifostine and curative intent chemoradiation for compromised cancer patients.

Concurrent chemotherapy and radiation are usually indicated for locally advanced carcinomas such as head and neck and anal malignancies. Because of the toxicity of the treatment, patient selection plays an important role in recommendations to treat with a curative intent. Elderly patients (> 70 years), those with underlying medical conditions or acquired immunological disorders (AIDS) are commonly excluded from combined modality therapy because of their perceived inability to tolerate the aggressive treatment. They may thus be deprived of a potentially curative therapy. In an attempt to improve outcome, we conducted a pilot study using amifostine, a radioprotector, to increase the tolerance of such compromised individuals to treatment. Amifostine (500 mg intravenously) was given during chemotherapy on days 1-5, and days 21-25 of radiation regimen. All patients were able to complete the chemoradiation. Despite the locally advanced stage of the disease, five out of our six patients achieved a complete response (CR). One patient with synchronous primaries had a complete response for the base of tongue cancer and regression of the esophageal cancer, which allowed him to resume oral feeding. All patients achieved improved quality of life. Successful chemoradiation appears to be feasible in patients with advanced stage, age and/or underlying medical conditions when amifostine is integrated in the treatment.

COX-2-specific inhibitors: prescribing patterns in a large managed care health system and strategies to minimize costs.

OBJECTIVE: To determine the relative costs associated with the exclusive use of celecoxib versus rofecoxib in a large managed care system. STUDY DESIGN: A retrospective review of all calendar year 2000 prescriptions dispensed for celecoxib and rofecoxib in the Veterans Affairs (VA) system. METHODS: The primary data points included drug strength, quantity dispensed, and days supply for the prescription. The cost minimization model described in Federal Practitioner (1999;16[4]:41-44) was used to calculate the cost savings. The mean once-daily dosing rates and their 95% confidence intervals were determined by binomial data analysis. Calendar year 2001 utilization and cost projections were derived by linear regression trend analysis. RESULTS: Current VA system costs per dose are celecoxib 100 mg $0.66; celecoxib 200 mg $1.32; rofecoxib (12.5 or 25 mg) $1.32; rofecoxib 50 mg $2.14. During calendar year 2000, the VA spent $13.8 million and $4.2 million on celecoxib and rofecoxib, respectively. The percentage of once-daily or less than once-daily dosing was celecoxib 100 mg (17%), celecoxib 200 mg (67%), celecoxib overall (49%), rofecoxib 12.5 mg (86%), rofecoxib 25 mg (94%), rofecoxib 50 mg (100%), and rofecoxib overall (93%). Based on current utilization, if all celecoxib prescriptions were changed to rofecoxib, the VA would have realized annual cost savings of $2.1 million in calendar year 2000. In calendar year 2001, projected cost savings could total $5.2 million. This potential savings is largely due to the high prevalence of twice-daily celecoxib dosing. CONCLUSION: The results of the cyclooxygenase-2 cost minimization analysis provide a compelling argument for the preferred use of rofecoxib in the VA system, and potentially in other managed care systems.