Risk of Urinary Infections in Veterans on Empagliflozin With Concurrent Catheter Use.

There has been concern over whether to use sodium-glucose-cotransporter-2 (SGLT-2) inhibitors in patients that use catheters due to the concern for increased urinary tract infections (UTIs). The concern is that patients who use catheters are already at an increased risk for UTIs and that SGLT-2-inhibitors may promote bacterial growth due their mechanism of action, ie. increasing glycosuria. The objective of this study was to evaluate whether using empagliflozin, a SGLT-2-inhibitor, in patients who also use catheters, increases their risks for UTIs. A retrospective chart review of electronic health records at a single-center was completed of all Veterans who received an empagliflozin prescription and were also using catheters between October 1, 2015 and September 30, 2022. Veterans were included if they were using catheters for at least 2 months prior to starting empagliflozin and were on both therapies for at least 2 months concurrently. The primary outcome for this study is the number of UTIs occurring prior to and after beginning empagliflozin treatment. Additional secondary outcomes included change in A1c, change in body mass index (BMI), UTI-hospitalizations, and fungal infections. Of the 91 patients with concurrent empagliflozin and catheter-use, only 25 Veterans were included. There was an occurrence of .09 UTIs/month pre-empagliflozin compared to .07 post-empagliflozin (P = .61). There was an observed trend in Veterans with Type 2 Diabetes having an increased rate of UTIs. There was no statistically significant difference found in UTI rates when comparing catheters alone to concurrent catheter and empagliflozin-use.

Microglia as a cellular target of diclofenac therapy in Alzheimer's disease.

Alzheimer's disease (AD) is an untreatable cause of dementia, and new therapeutic approaches are urgently needed. AD pathology is defined by extracellular amyloid plaques and intracellular neurofibrillary tangles. Research of the past decades has suggested that neuroinflammation plays a critical role in the pathophysiology of AD. This has led to the idea that anti-inflammatory treatments might be beneficial. Early studies investigated non-steroidal anti-inflammatory drugs (NSAIDS) such as indomethacin, celecoxib, ibuprofen, and naproxen, which had no benefit. More recently, protective effects of diclofenac and NSAIDs in the fenamate group have been reported. Diclofenac decreased the frequency of AD significantly compared to other NSAIDs in a large retrospective cohort study. Diclofenac and fenamates share similar chemical structures, and evidence from cell and mouse models suggests that they inhibit the release of pro-inflammatory mediators from microglia with leads to the reduction of AD pathology. Here, we review the potential role of diclofenac and NSAIDs in the fenamate group for targeting AD pathology with a focus on its potential effects on microglia.

Utilization of a neurology specialty service by primary care providers for headache management at a tertiary care hospital.

Background: Recent data indicate that the three-month prevalence of severe headaches or migraines in the US general population is close to 25%. Participation of primary care providers will therefore be critical in providing care to affected individuals. Objective: To determine the number of headache disorder consult requests to a neurology outpatient service in a tertiary medical center, the appropriateness of the consult requests, and the effectiveness of a lecture series on headache diagnosis and management in preventing inappropriate consult requests from non-neurology providers. Methods: Clinical data on US Veterans is captured and documented in the Veterans Health Information Systems and Technology Architecture (VISTA). The Computerized Patient Record System (CPRS) electronic medical record (EMR) was used for data entry and retrieval. All consult requests for the study period within the VA North Texas Health Care System were identified in VISTA, and the clinical information reviewed in CPRS. Based on a defined algorithm, headache consult request were categorized as appropriate or inappropriate. A board-certified neurologist provided four in-person/virtual lectures to ambulatory care providers, primary care providers, internal medicine residents, and emergency room providers within the VA North Texas Health Care System on the diagnosis and management of headaches. Prior and post the lecture series, the total number of headache consults per day was assessed over 45-day periods. Results: The number of daily headache consult requests in the 45-day period prior to the lecture series was 3.6 per day (standard deviation 2.7), and 6.0 per day after the lecture series (standard deviation 2.1). The difference was not statistically significant. There were as many inappropriate headache consult requests after the lecture series as appropriate ones (50% each). Conclusion: We found that a short-term educational initiative that instructed primary care providers on the diagnosis and management of common headache disorders did not reduce the number of consultation requests and, surprisingly, it did not improve the appropriateness of the consults. Given the prevalence of headaches in the general population, better training of all primary care providers in headache management should be pursued.

Phosphodiesterase 5 Inhibitor Use in Patients Undergoing Decompression Surgery for Lumbar Spinal Stenosis.

OBJECTIVE: Our objectives were to explore the association between phosphodiesterase 5 inhibitor use and lumbar decompression surgery by evaluating the prevalence of lumbar decompression surgery in a treatment group of patients with lumbar spinal stenosis compared with a control group. DESIGN: We performed database review and extracted data including lumbar decompression surgery prevalence, phosphodiesterase 5 inhibitor dosage, and fill dates. Treatment group was defined as those with phosphodiesterase 5 inhibitor fill dates of less than 30 days before surgery, and control group was defined as those with phosphodiesterase 5 inhibitor fill dates at any other time. Lumbar decompression surgery prevalence rates for both groups were calculated. RESULTS: Our study found 599 lumbar spinal stenosis patients who were prescribed phosphodiesterase 5 inhibitor. Three hundred thirty-eight underwent lumbar decompression surgery. Of these, 71 (21%) filled their prescription of less than 30 days before surgery, whereas 267 (79%) filled their prescription during a different period. The majority (94.6%) of surgical patients received decompression at two or more spinal levels. CONCLUSIONS: Prevalence of lumbar decompression surgery for lumbar spinal stenosis was significantly lower in patients in the treatment group on phosphodiesterase 5 inhibitor therapy compared with the control group. Among many potential explanations, the vasodilatory effect of phosphodiesterase 5 inhibitor may have contributed to a lower surgical rate. This is the first study to explore this novel association. Future prospective studies are necessary to better define the utility of phosphodiesterase 5 inhibitor in lumbar spinal stenosis.

Evaluation of Vitamin B12 Monitoring in Veterans With Type 2 Diabetes on Metformin Therapy.

BACKGROUND: Studies have shown an association between metformin use and vitamin B12 deficiency. Since 2017, the American Diabetes Association (ADA) Standards of Medical Care in Diabetes Guideline has included a recommendation for periodic vitamin B12 measurements in metformin-treated patients, especially those with anemia or peripheral neuropathy. OBJECTIVE: To determine the overall incidence and impact of the ADA Guideline on vitamin B12 monitoring in a veteran population on long-term metformin therapy. METHODS: Retrospective chart review was performed for patients on metformin who started therapy prior to 2005 at the VA North Texas Health Care System (VANTXHCS). The primary outcome was the proportion of patients with at least 1 vitamin B12 level drawn during 2016 versus 2018. Metformin dose and duration, vitamin B12 supplementation, and incident neuropathy prescriptions or diagnosis were also analyzed. RESULTS: Of 394 patients included for the primary outcome, 136 (34.5%) had at least 1 vitamin B12 level in 2016 versus 198 (50.3%) patients in 2018 (odds ratio: 1.94, P < .001). Of the 394 patients, 157 were diagnosed with neuropathy or prescribed a medication for neuropathy without a vitamin B12 level in the previous year or with a low level that was not supplemented. CONCLUSION: Vitamin B12 monitoring significantly increased between 2016 and 2018, aligning with the release of the 2017 ADA guidelines. However, a large proportion of patients were identified who were diagnosed with or treated for neuropathy without adequate vitamin B12 monitoring.

Diclofenac reduces the risk of Alzheimer's disease: a pilot analysis of NSAIDs in two US veteran populations.

BACKGROUND: Our aim was to determine whether specific nonsteroidal anti-inflammatory (NSAID) agents are associated with a decreased frequency of Alzheimer's disease (AD). MATERIALS AND METHODS: Days of drug exposure were determined for diclofenac, etodolac, and naproxen using US Department of Veterans Affairs (VA) pharmacy transaction records, combined from two separate VA sites. AD diagnosis was established by the International Classification of Diseases, ninth revision (ICD-9)/ICD-10 diagnostic codes and the use of AD medications. Cox regression survival analysis was used to evaluate the association between AD frequency and NSAID exposure over time. Age at the end of the study and the medication-based disease burden index (a comorbidity index) were used as covariates. RESULTS: Frequency of AD was significantly lower in the diclofenac group (4/1431, 0.28%) compared with etodolac (328/14,646, 2.24%), and naproxen (202/12,203, 1.66%). For regression analyses, naproxen was chosen as the comparator drug, since it has been shown to have no effect on the development of AD. Compared with naproxen, etodolac had no effect on the development of AD, hazard ratio (HR) 1.00 [95% confidence interval (CI): 0.84-1.20, p = 0.95]. In contrast, diclofenac had a significantly lower HR of AD compared with naproxen, HR 0.25 (95% CI: 0.09-0.68, p <0.01). After site effects were controlled for, age at end of the study (HR = 1.08, 95% CI: 1.07-1.09, p <0.001) was also found to influence the development of AD, and the medication-based disease burden index was a strong predictor for AD, HR 5.17 (95% CI: 4.60-5.81) indicating that as comorbidities increase, the risk for AD increases very significantly. CONCLUSION: Diclofenac, which has been shown to have active transport into the central nervous system, and which has been shown to lower amyloid beta and interleukin 1 beta, is associated with a significantly lower frequency of AD compared with etodolac and naproxen. These results are compelling, and parallel animal studies of the closely related fenamate NSAID drug class.

Safety of tumor necrosis factor inhibitor use in patients with concomitant malignancy.

BACKGROUND/AIMS: Safety for tumor necrosis factor inhibitors (TNFi) in cancer has been focused on risk of incident malignancies, but studies on prognostic effects have been scarce. We determined survival and recurrence rates at 1, 2, and 5 years after cancer diagnosis in patients with and without concurrent TNFi use. METHODS: Chart reviews were performed between 1996 and 2015 at the VA North Texas Healthcare System. Cases were patients with inflammatory disease, concomitant malignancy, and TNFi use while controls were patients with inflammatory disease, concomitant malignancy but no TNFi use. Cases and controls were matched for type of malignancy. Analysis was performed with log-rank tests on Kaplan-Meier curves. RESULTS: Thirty-six cases and 72 controls were identified. For cases, survival at 1, 2, and 5 years were 32 (89%), 31 (86%), and 29 (81%) compared to 63 (90%), 61 (87%), and 51 (73%) for the control group (P=0.985). For cases, recurrence rates at 1, 2, and 5 years were 3 (8%), 5 (14%), and 6 (17%) compared to 2 (3%), 5 (7%), and 7 (10%) for the control group (P=0.158). CONCLUSIONS: Our findings suggest TNFi may be safely used in select inflammatory disease patients with concurrent cancer if therapy is needed for proper disease control. However, case-by-case consideration in conjunction with an oncologist is recommended while considering the apparent safety of TNFi for patients suffering from active inflammatory diseases despite having a concomitant malignancy.

Intravenous Antiplatelet Therapy Bridging in Patients Undergoing Cardiac or Non-Cardiac Surgery Following Percutaneous Coronary Intervention.

BACKGROUND: The effect of perioperative bridging therapy on risks of ischemic cardiac events and major bleeding complications in patients on dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) remains undefined. METHODS: We report on 60 consecutive patients between 2010 and 2017 who required cardiac (CS; n = 15) or non-cardiac (NCS; n = 45) surgeries following PCI at our institution. Short-acting intravenous (IV) antiplatelet (APT) bridging with eptifibatide, tirofiban and cangrelor were instituted after DAPT interruption. RESULTS: All patients were men with multiple atherosclerosis risk factors. An acute coronary syndrome indication (56.7%) was the most common PCI indication in the CS and NCS groups. Drug-eluting stents were used in 93.33% and 95.56% of the above groups, respectively. The median duration from PCI to CS and NCS were 11.17 and 18.25 months, respectively and 38.33% of all surgeries were performed within 6 months of the index PCI. Most patients were on background aspirin (83.33%) and clopidogrel (81.67%) and median duration of DAPT interruption was 7 days. Median duration of perioperative IV APT bridging was 3 days for CS and 5 days for NCS groups. In the CS group, two patients (13.33%) had non-fata myocardial infarction (MI), and four (26.67%) had clinically significant bleeding. No patients had perioperative stent thrombosis. In the NCS group, one patient (2.22%) had stent thrombosis; four (6.67%) had myocardial infarction, and five (11.11%) clinically significant bleeding. CONCLUSIONS: Despite using IV APT as bridging therapy during perioperative DAPT interruption in post-PCI patients, postoperative cardiac events and bleeding complications can still occur.

Incidence of Colorectal Cancer and Extracolonic Cancers in Veteran Patients With Inflammatory Bowel Disease.

Background: The risk for colorectal cancer (CRC) and certain extracolonic cancers is thought to be increased in inflammatory bowel disease (IBD), but few recent US studies have evaluated this issue. We aimed to estimate the incidence of CRC and extracolonic cancers in IBD patients. Methods: In this case-control study, cases were all IBD patients treated in our Department of Veterans Affairs (VA) hospital who developed CRC or extracolonic cancers between 1996 and 2015. Controls were patients in the general VA population who developed these cancers during the same time. We compared cancer incidence rates (IRs) in cases and controls. Results: There was no significant difference between cases and controls in the 20-year IR for CRC (148/100 000 in IBD patients, 97/100 000 in controls; relative risk [RR], 1.53; 95% confidence interval [CI], 0.86-2.69). In contrast, IBD cases had a significantly higher 20-year IR for all extracolonic cancers than controls (2839/100 000 in IBD patients, 1960/100 000 in controls; RR, 1.45; 95% CI, 1.27-1.65). Site-specific analyses revealed that IBD patients had significantly elevated risks for nonmelanoma skin cancers (RR, 2.38; 95% CI, 1.99-2.85), melanoma skin cancers (RR, 2.85; 95% CI, 1.63-4.88), renal tumors (RR, 2.90; 95% CI, 1.46-5.84), prostate cancer (RR, 1.70; 95% CI, 1.28-2.27), and pancreatic cancer (RR, 4.23; 95% CI, 1.35-13.29). Conclusions: The incidence of CRC was not significantly higher in our veteran patients with IBD than in control patients in the general VA population. In contrast, our IBD patients had a significantly higher risk for extracolonic cancers than controls, including cancers of the skin, kidneys, prostate, and pancreas. 10.1093/ibd/izx046_video1Video 1.izx046_Mosher_Video5734484616001.

Factors Associated With Length of Stay in Veterans With Inflammatory Bowel Disease Hospitalized for an Acute Flare.

Background: Reducing hospital costs and risk of complications by shortening length of stay has become paramount. The aim of our study was to identify predictors and potentially modifiable factors that influence length of stay among veterans with inflammatory bowel disease admitted for an acute flare. Methods: Retrospective review of patients admitted to the Dallas VA with an acute flare of their inflammatory bowel disease between 2000 and 2015. Patients with a length of stay of ≤4 days were compared with those whose length of stay >4 days. Results: A total of 180 admissions involving 113 patients (59 with ulcerative colitis and 54 with Crohn's disease) were identified meeting inclusion criteria. The mean length of stay was 5.3 ± 6.8 days, and the median length of stay was 3.0 days. On multiple logistic regression analysis, initiation of a biologic, having undergone 2 or more imaging modalities, and treatment with intravenous steroids were significant predictors of longer lengths of stay, even after controlling for age and comorbid diseases. Conclusions: We identified several predictors for longer hospital length of stay, most related to disease severity but several of which may be modifiable to reduce hospital stays, including most importantly consideration of earlier prebiologic testing. Future studies are needed to evaluate the impact of interventions targeting modifiable predictors of length of stay on health care utilization and patient outcomes.

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.

Significance of an abnormal ankle-brachial index in patients with established coronary artery disease with and without associated diabetes mellitus.

An abnormal ankle-brachial index (ABI) is associated with higher risk for future cardiovascular (CV) events; however, it is unknown whether this association is true in patients with established coronary artery disease (CAD) and associated diabetes mellitus (DM). We evaluated 679 patients with stable CAD enrolled in the Excellence in Peripheral Arterial Disease and Veterans Affairs North Texas Healthcare System peripheral arterial disease databases. ABI and 12-month major adverse CV events (MACEs, a composite of all-cause death, nonfatal myocardial infarction, need for repeat coronary revascularization, and ischemic stroke) were assessed. Cox proportional hazard models were used to assess the association of ABI and DM with subsequent CV events. An abnormal ABI (<0.9 or >1.4) was present in 72% of patients with stable CAD and 68% had DM. Using patients without DM and normal ABI as reference, the adjusted hazard ratio for 12-month MACE was 1.7 (95% confidence interval [CI] 0.71 to 4.06) for patients with DM and normal ABI; 2.03 (95% CI 0.83 to 4.9) for patients without DM with abnormal ABI; and 4.85 (95% CI 2.22 to 10.61) for patients with DM and abnormal ABI. In conclusion, in patients with stable CAD, an abnormal ABI confers an incremental risk of MACE in addition to DM and traditional CV risk factors.

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).

Proton pump inhibitors increase the incidence of bone fractures in hepatitis C patients.

BACKGROUND: While proton pump inhibitors (PPI) may increase the risk of bone fractures, the incidence of new bone fractures in a chronic hepatitis C virus (HCV) infected cohort, with or without PPI exposure, has not been explored. METHODS: A retrospective cohort study of the incidence of bone fractures over 10 years in 9,437 HCV antibody positive patients in the Dallas VA Hepatitis C Registry was performed. The study endpoint was the incidence of verified new bone fractures per patient-years (pt-yrs) in PPI users compared to non-PPI users. PPI use was defined as those taking a PPI for ≥360 days. Pt-yrs of exposure for PPI users began on the first PPI prescription date, and pt-yrs of exposure for non-PPI users began with first date of any non-PPI prescription. For both HCV groups, the final date of patients' study duration was defined by end of PPI exposure, bone fracture occurrence, death or end of study evaluation period. Exclusion criteria included use of bone health modifying medications ≥30 days. Statistical differences in fracture incidence between groups were determined by multivariate regression analysis. RESULTS: Among the total study population analyzed (n = 2,573), 109 bone fractures occurred. Unadjusted bone fracture incidences were 13.99/1,000 pt-yrs vs. 5.86/1,000 pt-yrs in PPI and non-PPI users, respectively. The adjusted hazard ratio for new bone fractures was 3.87 (95 % CI 2.46-6.08) (p < 0.001) in PPI users. CONCLUSIONS: In patients with chronic HCV, use of PPI for >1 year increased the risk of new bone fractures by more than threefold.

The clinical relevance of the clopidogrel-proton pump inhibitor interaction.

Proton pump inhibitors are often prescribed concomitantly with clopidogrel and aspirin to patients post-percutaneous coronary interventions and/or an acute coronary syndrome to mitigate the risk of potential gastrointestinal bleeding, associated primarily with clopidogrel use. Over the last several years, there have been data both supporting and refuting a clopidogrel-proton pump inhibitor interaction. This review critically considers the current evidence and provides practical recommendations to healthcare providers.

Predictors of hyperkalemia and death in patients with cardiac and renal disease.

Predictors of hyperkalemia in patients with cardiovascular disease (CVD; defined as patients with hypertension and heart failure) and associated chronic kidney disease (CKD) are not well established. The aim of this study was to ascertain risk factors of hyperkalemia (defined as serum potassium concentration >5.0 mEq/L) and associated all-cause mortality in patients with CVD treated with antihypertensive drugs that impair potassium homeostasis. In a retrospective analysis using a logistic regression model, risk factors for hyperkalemia and all-cause mortality were analyzed in 15,803 patients with CVD treated with antihypertensive drugs. The mean estimated glomerular filtration rate and mean serum potassium concentration were 55.55 ml/min/1.73 m(2) and 4.06 mEq/L, respectively. Hyperkalemia was observed in 24.5% of study patients and 1.7% of total hospital admissions. Compared to patients with normokalemia, those with hyperkalemia had a higher percentage of death (6.25% vs 2.92%, p = 0.0001) and admissions (7.80% vs 5.04%, p = 0.0001). Predictors of hyperkalemia were CKD stage (odds ratio [OR] 2.14, 95% confidence interval [CI] 2.02 to 2.28), diabetes mellitus (OR 1.59, 95% CI 1.47 to 1.72), coronary artery disease (OR 1.32, 95% CI 1.21 to 1.43), and peripheral vascular disease (OR 1.55, 95% CI 1.36 to 1.77). Predictors of all-cause mortality were CKD stage (OR 1.26, 95% CI 1.12 to 1.43), hyperkalemic event (OR 1.56, 95% CI 1.30 to 1.88), age (OR 1.04, 95% CI 1.03 to 1.05), and hospitalization (OR 1.04, 95% CI 1.04 to 1.05). In conclusion, hyperkalemia is encountered frequently in patients with established CVD who are taking antihypertensive drugs and is associated with increases in all-cause mortality and hospitalizations. Advanced CKD, diabetes mellitus, coronary artery disease, and peripheral vascular disease are independent predictors of hyperkalemia.

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.

Thiazides diuretics in the treatment of nephrolithiasis: are we using them in an evidence-based fashion?

In the 1980s a change occurred in hydrochlorothiazide prescribing practices for hypertension from high-dose (50 mg/day) to low-dose (12.5-25 mg/day) therapy. However, randomized controlled trials (RCT) for prevention of calcium-containing kidney stones (CCKS) employed only high doses (≥ 50 mg/day). We hypothesized that these practices have resulted in underdosing of hydrochlorothiazide for prevention of CCKS. Patients with a filled prescription for thiazide diuretics that underwent a 24-h urine stone risk factor analysis were eligible. Those with evidence that thiazide was prescribed for CCKS were further analyzed. Of 107 patients, 102 were treated with hydrochlorothiazide, 4 with indapamide, and one with chlorthalidone. Only 35% of hydrochlorothiazide-treated patients received 50 mg/day; a dose previously shown to reduce stone recurrence. Fifty-two percent were prescribed 25 mg and 13% 12.5 mg daily, doses that were not studied in RCT. Evidence-based hydrochlorothiazide use was suboptimal regardless of where the patient received care (Nephrology or Endocrinology clinic). In a small subset of patients (n = 6) with 24-h urinary calcium excretion measured at baseline and after 2 hydrochlorothiazide doses (25 and ≥ 50 mg), there was a trend toward decreased urinary calcium excretion as the dose was increased from 25 to ≥ 50 mg/day (p = 0.051). Low-dose hydrochlorothiazide was often used for prevention of CCKS despite the fact that there is no evidence that it is effective in this setting. This may have resulted from a practice pattern of using lower doses for hypertension therapy or a lack of knowledge of RCT results in treatment of CCKS.