Plasma Trimethylamine N-Oxide Levels Are Associated with Poor Kidney Function in People with Type 2 Diabetes.

Previous studies have linked elevated plasma trimethylamine N-oxide (TMAO) levels to poor renal function. The relationship between TMAO and chronic kidney disease (CKD) in type 2 diabetes (T2D) is still unclear. We investigated the association between plasma TMAO levels and CKD in patients with T2D. A cross-sectional study of 133 patients with T2D with or without CKD has been conducted. Blood biomarkers of kidney function, diabetes, and inflammation were assessed in the study participants. Plasma TMAO levels were quantified using UPLC-MS/MS. People with T2D and CKD exhibited significantly higher plasma TMAO levels [10.16 (5.86-17.45) µmol/L] than those without CKD [4.69 (2.62-7.76) µmol/L] (p = 0.002). Participants in the highest quartile of TMAO levels (>8.38 µmol/L) presented relatively elevated serum creatinine levels and a higher number of people with CKD than those in the lower quartiles. TMAO levels were significantly correlated with kidney function biomarkers, including estimated glomerular filtration rate and urinary albumin to creatinine ratio. The association between TMAO and CKD was evident (p < 0.0001) and remained significant after adjusting for risk factors of kidney disease, including age, gender, body mass index, duration of diabetes, and smoking. These findings suggest the association between plasma TMAO and CKD in patients with T2D.

Association between Plasma Trimethylamine N-Oxide Levels and Type 2 Diabetes: A Case Control Study.

Animal and human studies have reported conflicting results on the relationship between circulating trimethylamine N-oxide (TMAO) levels and risk of Type 2 diabetes (T2D). This study aimed to compare plasma TMAO levels in people with or without T2D and explore the association of TMAO and T2D. A prospective case-control study of 297 participants, 164 healthy controls and 133 patients with T2D, was conducted. TMAO levels were quantified by UPLC-MS/MS. Comorbidities, dietary patterns, physical activity, and blood biomarkers were assessed. Median (IQR) plasma TMAO levels were significantly higher in diabetes cases (4.95 (2.84−8.35) µmol/L) compared to healthy controls (3.07 (2.05−4.82) µmol/L) (p < 0.001). The association between TMAO and T2D was significant in the non-adjusted Model 1 (p < 0.001) and after adjusting for confounders of diabetes including age, BMI, and level of education in Model 2 (p = 0.04). When the association was further adjusted for physical activity and diet in Model 3, plasma TMAO levels at only the highest quartile (>6.40 µmol/L) were associated with the risk of diabetes (OR = 3.36, 95% CI [1.26, 9.04], p = 0.02). The results presented suggest an association between plasma TMAO levels and T2D. A significant correlation was found between red meat consumption and increased levels of TMAO in T2D patients. A longitudinal study is warranted to further evaluate the correlation between TMAO and T2D.

Evaluation of Cytotoxic and Tyrosinase Inhibitory Activities of 2-phenoxy(thiomethyl) pyridotriazolopyrimidines: In Vitro and Molecular Docking Studies.

BACKGROUND: The use of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies. OBJECTIVE: The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines. METHODS: MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the Tyrosinase (TYR) inhibitory activity of the targets. RESULTS: The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitory test. Compounds 2b, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the Structure-Activity Relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase. CONCLUSION: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors.

Identifying factors and target preventive therapies for Middle East Respiratory Syndrome sucsibtable patients.

BACKGROUND: Middle East Respiratory Syndrome (MERS) is a respiratory disease caused by a novel coronavirus that was identified in 2012 in Saudi Arabia. It is associated with significant mortality and morbidity. We identified factors associated with the Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) infection among suspected cases presented with sign and symptoms of upper respiratory infection or exposure to the virus. We also looked at the impact of medication history on virus transmission. METHOD: We included subjects with suspected MERS-CoV infection and confirmed cases of MERS infection. Subjects were excluded if there were any missing data that prevent the final analysis. Descriptive statistics were used to report demographic data. Percentages and frequencies were used to summarize the categorical variables, while means and standard deviations were calculated for continuous variables. Logistic regression was used to assess the risk of MERS-CoV infection among the suspected cases. A value of p < 0.05 was considered statistically significant. RESULTS: A total of 16,189 suspected cases were identified, complete data were analyzed for 3154 to assess factors that are independently associated with MERS-CoV infection. MERS-CoV infection was associated with age (adjusted odds ratio [AOR] = 1.06; 95% CI [1.02-1.098], P-value = 0.004), male gender (AOR = 1.617; 95% CI [1.365-1.77], P-value < 0.001) and diabetes (AOR = 1.68; 95% CI [1.346-1.848], P-value = 0.002. There was no significant association with the other comorbidities. Medication history was not associated with an increase or decrease the likelihood of the infection. CONCLUSIONS: MERS-Cov infection is more common in male, advanced age and diabetes. No medications were associated with an increase or decrease the likelihood of the infection. This is important to focus on screening and detection to this patient population.

Health literacy among patients with poor understanding of prescription drug label instructions in Saudi Arabia.

INTRODUCTION: This study conducted to assess the health literacy level among patients who have poor understanding of the medications' labels in Saudi Arabia. METHODS: This multi-center cross-sectional study was conducted on two phases. In the 1st phase, 511 patients waiting for their medications in the outpatient pharmacies of four major hospitals in Saudi Arabia were interviewed to assess their understanding ability of the labels of five of the commonly prescribed medications. Those participants who misunderstood the medications' labels were enrolled in the 2nd phase of the study to assess their health literacy level. The validate Arabic Single Item Literacy Screener (SILS) was used to assess the health literacy level. ANALYSIS: The sample characteristics were described by mean and percentage. Both Chi-square test and logistic regression model were used to figure out the association between health literacy with the main affecting factors. RESULTS: Almost 38.6% (n = 197) of the participants in phase-1 misunderstood the medications' labels. Nearly, 11.2% (n = 22) of them had low health literacy level. Participants who had low education level and low socioeconomic status were more likely to have low health literacy [adjusted odds ratio (AOR) = 2.94; 95% confidence interval (95%CI) (1.03-8.404); P-value = 0.044], [AOR = 5.28; 95%CI (1.118-24.943); P-value = 0.036], respectively. CONCLUSION: Low health literacy was associated with low education level and low socioeconomic status of the patients.

Modulation of Circulating Trimethylamine N-Oxide Concentrations by Dietary Supplements and Pharmacological Agents: A Systematic Review.

Discovery of the association of plasma/serum trimethylamine N-oxide (TMAO) concentrations with atherosclerosis has sparked immense interest in exploring TMAO as a predictor of cardiovascular disease risk. A spectrum of antibiotics and other therapeutic strategies have been employed to test their potential to modulate TMAO concentrations, assuming the gut microbiome to be the key source of TMAO. The aim of this systematic review was to determine whether dietary supplements or pharmacological agents affect TMAO concentrations in adults. Six databases were searched (Medline, EMBASE, CINAHL, Scopus, ProQuest, and PubMed) for randomized and nonrandomized controlled trials. Searches were limited to the English language and to studies in adults. Thirteen eligible trials were identified, including 6 studies on dietary supplements and 7 on pharmacological agents. Whereas intervention studies involving dietary supplements were mostly randomized controlled trials, those involving pharmacological agents appeared opportunistic and varied greatly in study design and duration. Different interventional products were tested, and the studies lacked the consistency to reliably synthesize any evidence for the modifiability of TMAO concentrations by dietary supplements or pharmacological agents. Choline and l-carnitine are conditionally essential nutrients, and carefully designed placebo-controlled randomized trials specifically aimed at reducing the synthesis of microflora-dependent TMAO production from choline-containing precursors by pro- and/or prebiotics, antibiotics, or other pharmaceutical agents may be the way forward for future research.

Radioiodination and biodistribution of newly synthesized 3-benzyl-2-([3-methoxybenzyl]thio)benzo[g]quinazolin-4-(3H)-one in tumor bearing mice.

3-Benzyl-2-((3-methoxybenzyl)thio)benzo[g]quinazolin-4(3H)-one was previously synthesized and proved by physicochemical analyses (HRMS, 1H and 13C NMR). The target compound was examined for its radioactivity and the results showed that benzo[g]quinazoline was successfully labeled with radioactive iodine using NBS via an electrophilic substitution reaction. The reaction parameters that affected the labeling yield such as concentration, pH and time were studied to optimize the labeling conditions. The radiochemical yield was 91.2 ±â€¯1.22% and the in vitro studies showed that the target compound was stable for up to 24 h. The thyroid was among the other organs in which the uptake of 125I-benzoquinazoline has increased significantly over the time up to 4.1%. The tumor uptake was 6.95%. Radiochemical and metabolic stability of the benzoquinazoline in vivo/in vitro and biodistribution studies provide some insights about the requirements for developing more potent radiopharmaceutical for targeting the tumor cells.

Liver enzyme trends in patients taking uninterrupted metformin before and after coronary surgery.

BACKGROUND: Metformin is an oral antidiabetic agent belonging to the biguanide class of antidiabetics. Possible novel applications for metformin in cardiovascular disease might exist. The aim of this study was to verify a possible association between pre-operative metformin administration and protection against ischemia-induced liver injury in diabetic patients undergoing coronary artery bypass grafting (CABG) surgery. METHODS: A retrospective case-control series was conducted at a single center. Two hundred consecutive diabetic patients underwent isolated on-pump CABG during a 12-month span (July 2015 - July 2016). Metformin was uninterrupted in patients who took this drug prior to CABG; 68 patients were metformin users (34%) while 132 patients were taking other antidiabetic agents (66%). Liver enzymes and other organ markers were consecutively recorded daily for 7 days after surgery and expressed as medians with interquartile range (IQR). RESULTS: Both the metformin and non-metformin group of patients had similar pre-operative demographic characteristics. The median (IQR) post-operative cardiac enzyme creatinine kinase (CK) MB fraction was significantly lower in the metformin group [46.4 U/L (35.8-66.5) vs. 66.5 U/L (44-94.5), P=0.005]. Total bilirubin [0.58 (0.48-0.82) mg/dL vs. 0.67 (0.56-0.95) mg/dL, P=0.021], the transaminase aspartate aminotransferase (AST) [32.5 U/L (25.0-42.0) vs. 37.5 U/L (28.5-56), P=0.011], the transaminases alanine aminotransferase (ALT) [48.5 U/L (40.0-64.0) vs. 57.0 U/L (44.0-77.0), P=0.040] and lactate dehydrogenase (LDH) [320.0 U/L (273.5-367.2) vs. 356.5 U/L (289.5-427), P=0.014] were significantly lower in the metformin group. No differences were noted in clinical outcomes. CONCLUSIONS: In this limited retrospective study, the diabetic patients who took metformin before and after undergoing CABG appeared to have a reduced post-operative surge in the total bilirubin and transaminase liver enzymes. Metformin's role in mitigating oxidative stress in liver cells might explain this observation. Further experimental studies are warranted to verify this possible effect.

Transient liver dysfunction increases surgical site infections after coronary surgery.

Background Surgical site infections can have a significant impact on cardiac surgical outcome. The liver plays an important role in infection prevention. This study aimed to retrospectively determine whether transient postoperative liver dysfunction after coronary bypass surgery increased surgical site infections. Methods A modified version of the Schindl scoring scale for liver dysfunction was adapted to objectively quantify transient liver dysfunction in the first 7 days after on-pump coronary artery bypass grafting. A retrospective analysis of clinical outcomes at 30 months postoperatively was performed on data of 575 patients who underwent coronary artery bypass between 2014 and 2016. The patients were categorized into a liver dysfunction group (Schindl score ≥ 4) and a non-liver dysfunction group (Schindl score < 4). Results The liver dysfunction group (47.3%) had significantly more patients who were obese, current smokers, and had diabetes, renal impairment, and peripheral vascular disease. Surgical site infections occurred predominantly in the liver dysfunction group (12.1% vs. 0.3%, p < 0.001). The independent predictors of surgical site infection were liver dysfunction, body mass index > 30 kg m-2, and coronary bypass surgery combined with other cardiac procedures. Conclusions Surgical wound infections can be precipitated by multiple factors before, during, and after coronary bypass surgery. Transient liver dysfunction in the perioperative period is associated with an increased rate of surgical infections even after adjusting for known risk factors. Considering this factor as well as other known risks may help to identify and stratify patients with a potentially higher risk of surgical site infections.

Guideline-Directed Medical Therapy and Survival Following Hospitalization in Patients with Heart Failure.

BACKGROUND: Modification of guideline-directed medical therapy (GDMT) in hospitalized patients with heart failure (HF) has not been extensively evaluated. METHODS: The community surveillance arm of the Atherosclerosis Risk in Communities Study identified 6959 HF hospitalizations from 2005-2011. Predictors of GDMT modification and survival were assessed using multivariable logistic regression and Cox proportional hazards models. RESULTS: For 5091 hospitalizations, patient mean age was 75 years, 53% were female, 69% were white, and 81% had acute decompensated heart failure (ADHF). Regarding ejection fraction (EF), 31% of patients had HF with reduced EF (HFrEF), 24% had HF with preserved EF (HFpEF), and 44% were missing EF values. At admission, 52% of patients received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), 66% ß-blockers (BBs), 9% aldosterone-receptor antagonists, 16% digoxin, 10% hydralazine, and 29% nitrates. Modification of GDMT occurred in up to 23% of hospitalizations. Significant predictors of GDMT initiation included ADHF and HFrEF; discontinuation of medications was observed with select comorbidities. In HFrEF, initiation of any GDMT was associated with reduced 1-year all-cause mortality (adjusted hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.23-0.71) as was initiation of ACEI/ARBs, BBs, and digoxin. Discontinuation of any therapy versus maintaining GDMT was associated with greater mortality (HR 1.30, 95% CI 1.02-1.66). Similar trends were observed in HFpEF. CONCLUSIONS: Our study suggests that GDMT initiation is associated with increased survival, and discontinuation of therapy is associated with reduced survival in hospitalized patients with HF. Future studies should be conducted to confirm the impact of GDMT therapy modification in this population.

Advancing pharmaceuticals and patient safety in Saudi Arabia: A 2030 vision initiative.

Low-quality medicines deliver sub-optimal clinical outcomes and waste precious health resources. It is important to ensure that public funds are spent on healthcare technologies that meet national regulatory bodies such as the Saudi Food and Drug Authority (SFDA), quality standards for safety, efficacy, and quality. Medicines quality is a complicated combination of pre-market regulatory specifications, appropriate sourcing of ingredients (active pharmaceutical ingredient (API), excipients, etc.), manufacturing processes, healthcare ecosystem communications, and regular and robust pharmacovigilance practices. A recent conference in Riyadh, sponsored by King Saud University, sought to discuss these issues and develop specific policy recommendations for the Saudi 2030 Vision plan. This and other efforts will require more and more creative educational programs for physicians, pharmacists, hospitals, and patients, and, most importantly evolving regulations on quality standards and oversight by Saudi health authorities.

The utilization of nonprescription medications in Saudi patients with cardiovascular diseases.

BACKGROUND: Cardiovascular diseases (CVDs) are the most common cause of disease-related death in Saudi Arabia. The incidence of CVDs continues to increase, presenting a major health care problem. Nonprescription medications are widely used by patients with CVD and may cause adverse drug events, either by worsening the disease or by harmfully interacting with prescribed medications. We investigated the patterns of nonprescription medication utilization and the factors associated with their use in patients with CVD. METHODS: This was a cross-sectional study conducted at the Cardiology Clinics of an academic tertiary health care center. Participants were asked about their sociodemographic characteristics, medical history and frequency of using nonprescription medications including over-the-counter (OTC) products, dietary supplements, and herbal products. Moreover, we investigated the participants' sources of information about nonprescription medications. Multivariate logistic regression analysis was conducted to examine the predictors of nonprescription medication use. RESULTS: A total of 209 participants were interviewed. The mean age of the participants was 56 ± 15 years, and 110 (52.6%) were female. Of the 209 participants, 116 (55%) reported routine use of nonprescription medications. Black seeds and garlic were the most frequently used herbal products. Acetaminophen, cold/cough remedies, and ibuprofen were the most commonly reported OTC drugs. Of the surveyed patients, 54 (46.5%) used nonprescription medications to manage cardiovascular conditions specifically. Compared with other comorbidities, diabetes mellitus was associated with a higher use of nonprescription medications. CONCLUSION: In patients with CVD, the routine use of nonprescription medications was common for a number of reasons. Health care providers should proactively discuss nonprescription use with their CVD patients to avoid potential harmful outcomes.

Patients' understanding of prescription drug label instructions in developing nations: The case of Saudi Arabia.

BACKGROUND: Processing health-related data is challenging for patients. It is believed that low education level and low socioeconomic status are associated with prescription label misunderstanding, which may lead to poor clinical outcomes, increased adverse drug reactions, and increased health costs. OBJECTIVES: The aim of this study was to gain a better insight into the current understanding of prescription drug labels, and to determine the main factors affecting patients' understanding of prescription labels. METHOD: A total of 511 adult participants in 4 major hospitals in Riyadh were interviewed. The primary outcome was patient understanding of prescription labels for 5 commonly prescribed medications. Prescription label understanding was assessed using a prespecified structured interview protocol. Participants with less than a 6th-grade education level and monthly income less than 10,000 Saudi Riyal were considered to have a low education level and low monthly income, respectively. Logistic regression analysis was used to examine the cross-sectional association of socioeconomic factors with the participants' understanding of the medication label. RESULTS: The prevalence of poor understanding of the medication labels was 38.6% among the participants. Out of those participants with poor understanding, 27.9% incorrectly understood at least 4 of the 5 labels. The degree of misunderstanding significantly worsened for older participants (P-value = 0.004), male (P-value < 0.001), with low education level (P-value = 0.002), and low monthly income (P-value = 0.012). The most common features misunderstood were duration of treatment (38.9%) and storage instructions (29.5%). CONCLUSIONS: Prescription label misunderstanding is common among participants. More efforts should be made to improve patients' understanding by reducing the ambiguity of the prescription labels.

Predictors of Medication Adherence in the Elderly: The Role of Mental Health.

The aging population routinely has comorbid conditions requiring complicated medication regimens, yet nonadherence can preclude optimal outcomes. This study explored the association of adherence in the elderly with demographic, socioeconomic, and disease burden measures. Data were from the fifth visit (2011-2013) for 6,538 participants in the Atherosclerosis Risk in Communities Study, conducted in four communities. The Morisky-Green-Levine Scale measured self-reported adherence. Forty percent of respondents indicated some nonadherence, primarily due to poor memory. Logit regression showed, surprisingly, that persons with low reading ability were more likely to report being adherent. Better self-reported physical or mental health both predicted better adherence, but the magnitude of the association was greater for mental than for physical health. Compared with persons with normal or severely impaired cognition, mild cognitive impairment was associated with lower adherence. Attention to mental health measures in clinical settings could provide opportunities for improving medication adherence.

Use of the guidelines directed medical therapy after coronary artery bypass graft surgery in Saudi Arabia.

Background: incidence of cardiovascular diseases in Saudi Arabia is growing and more patients are expected to have cardiac revascularization surgery. Optimal pharmacotherapy management with Guideline Directed Medical Therapy (GDMT) post coronary artery bypass grafting (CABG) plays an important role in the prevention of adverse cardiovascular outcomes. The objective of this study was to assess the utilization of GDMT for secondary prevention in CABG patients and determine whether specific patients' characteristics can influence GDMT utilization. Method: A retrospective chart review of patients discharged from the hospital after CABG surgery from April 2015 to April 2016. The primary outcome was the utilization of secondary prevention GDMT after CABG surgery - aspirin, B-blockers, statin and angiotensin-converting enzyme inhibitors (ACEI) (or angiotensin receptor blockers (ARB) in ACEI-intolerant patients). The proportions of eligible and ideal patients who received treatment were calculated, and mixed-effects logistic regression was used to estimate odds ratios (OR) for the association of age, gender or patient nationality with the use of GDMT. Results: A total number of 119 patients included in the analysis. The median age of the cohort was 57.3 ± 11 years, and 83% were male (83.2%). Nearly 69.7% of patients had diabetes, and 82% had a previous diagnosis of hypertension. Nearly 91% received aspirin therapy and the rate was lower for B-blocker and statin. The rate of GDMT utilization did not change with the change in patient's age, gender or nationality. Conclusion: Despite adjustments for contraindications to GDMT, the rate of GDMT utilization was suboptimal.

Utilization and adherence to guideline-recommended lipid-lowering therapy at an academic medical center.

BACKGROUND: Clinical guidelines for managing blood cholesterol were updated in November 2013. OBJECTIVE: To evaluate the adherence to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations for statin therapy in the treatment of elevated blood cholesterol in high-risk patients. DESIGN: A single-center, retrospective, observational study. SETTING: A tertiary care academic medical center in Riyadh, Saudi Arabia. PATIENTS: Consecutive adult patients discharged with a prescription for any of the statin medications group between 1 June 2015 and 31 December 2015. MAIN OUTCOME MEASURE(S): Adherence to the 2013 ACC/AHA guidelines for management of cholesterol by statin therapy in high-risk patients. RESULTS: Of 1094 patients, 753 (68.8%) met the inclusion criteria of the study. Of these 753 patients, 53.5% had atherosclerotic cardiovascular diseases; 29.2% had diabetes; 0.9% had an LDL-C level > 190 mg/dL; 10.8% had an estimated 10-year risk > 7.5%; and 4.9% had no risk. Two hundred and eight (27.6%) patients received statin therapy at an inappropriate intensity according to their risk group based on the guideline; 126 (16.7%) received less than the ideal intensity. CONCLUSION: Approximately one-third of patients received statin therapy at an inappropriate intensity according to the guideline recommendation. Wide application of the 2013 ACC/AHA cholesterol guidelines in our practice would optimize the utilization of statin therapy at the ideal intensity in high-risk patients. LIMITATION: Drug-drug interactions and intolerance to statin therapy were not considered when we evaluated adherence among high-risk patients.

Contribution of medications and risk factors to QTc interval lengthening in the atherosclerosis risk in communities (ARIC) study.

RATIONALE, AIMS, AND OBJECTIVES: Prolongation of the corrected QT (QTc) interval is associated with increased morbidity and mortality. The association between QTc interval-prolonging medications (QTPMs) and risk factors with magnitude of QTc interval lengthening is unknown. We examined the contribution of risk factors alone and in combination with QTPMs to QTc interval lengthening. METHOD: The Atherosclerosis Risk in Communities study assessed 15 792 participants with a resting, standard 12-lead electrocardiogram and ≥1 measure of QTc interval over 4 examinations at 3-year intervals (1987-1998). From 54 638 person-visits, we excluded participants with QRS ≥ 120 milliseconds (n = 2333 person-visits). We corrected the QT interval using the Bazett and Framingham formulas. We examined QTc lengthening using linear regression for 36 602 person-visit observations for 14 160 cohort members controlling for age ≥ 65 years, female sex, left ventricular hypertrophy, QTc > 500 milliseconds at the prior visit, and CredibleMeds categorized QTPMs (Known, Possible, or Conditional risk). We corrected standard errors for repeat observations per person. RESULTS: Eighty percent of person-visits had at least one risk factor for QTc lengthening. Use of QTPMs increased over the 4 visits from 8% to 17%. Among persons not using QTPMs, history of prolonged QTc interval and female sex were associated with the greatest QTc lengthening, 39 and 12 milliseconds, respectively. In the absence of risk factors, Known QTPMs and ≥2 QTPMs were associated with modest but greater QTc lengthening than Possible or Conditional QTPMs. In the presence of risk factors, ≥2 QTPM further increased QTc lengthening. In combination with risk factors, the association of all QTPM categories with QTc lengthening was greater than QTPMs alone. CONCLUSION: Risk factors, particularly female sex and history of prolonged QTc interval, have stronger associations with QTc interval lengthening than any QTPM category alone. All QTPM categories augmented QTc interval lengthening associated with risk factors.

Metformin is not associated with lactic acidosis in patients with diabetes undergoing coronary artery bypass graft surgery: a case control study.

BACKGROUND: Metformin associated lactic acidosis (MALA) is a rare but lethal complication. There is no consensus regarding when to stop and resume metformin in patients who undergo coronary artery bypass grafting (CABG). This study aimed to determine if uninterrupted metformin administration in patients with diabetes undergoing CABG increases the risk of lactic acidosis. METHODS: Over a span of 12 months (2015-2016), 127 patients with type 2 diabetes underwent isolated CABG. Of those, 41 patients (32%) continued taking metformin and 86 patients (68%) took other antidiabetic agents. Patients taking metformin took the drug until the day of surgery and resumed taking it 3 h after extubation. RESULTS: There were no differences in clinical outcomes or complications between groups. Serial measurement of cardiac, liver, and kidney biomarkers were similar between groups. The mean peak lactic acid level was significantly higher in the non-metformin users (5.4 ± 2.6 vs. 7.4 ± 4.1 mmol/l; P = 0.001). Multivariable logistic regression analysis identified the need for vasopressor administration as an independent predictor of lactic acidosis (odds ratio: 7.3, 95% confidence interval: 2.5-20.6; P < 0.001). CONCLUSION: In the absence of risk factors associated with persistent lactic acidosis, such as shock or acute kidney or liver injury, continued peri-operative metformin administration was not associated with the occurrence of lactic acidosis in patients undergoing CABG. Elevated lactic acid levels seem to be directly related to tissue anoxia caused by escalating vasopressor support after surgery.

Warfarin and Aspirin Versus Warfarin Alone for Prevention of Embolic Events in Patients with a HeartMate II Left Ventricular Assist Device.

Acquired von Willebrand disease increases bleeding risk in patients implanted with a continuous-flow left ventricular assist device. Lower aspirin (ASA) doses decrease the risk of bleeding without an increased risk of embolic events. No published studies in the United States have compared the incidence of bleeding and thrombotic events between antithrombotic regimens with and without ASA. A single-center, retrospective analysis was conducted of adult patients implanted with a HeartMate II (HM II). Patients received warfarin and ASA 81 mg daily or warfarin alone. The primary end-point was a composite of death, bleeding events, and thrombotic events from the date of HM II implantation to first event or 18 months. Secondary end-points included the individual components of the primary end-point and the proportion of patients alive with HM II or transplanted. The Wilcoxon rank sum test and Fisher's exact test were used for statistical analysis. Of the 76 patients meeting inclusion criteria, 44 received warfarin and ASA and 32 received warfarin alone. Baseline characteristics were similar between groups. Warfarin alone was not associated with an increased risk of the primary composite outcome (53 vs. 59%, respectively, p = 0.64). No significant difference was observed in any bleeding event (34 vs. 43%, respectively, p = 0.48) nor any thrombotic event (9 vs. 11%, respectively, p = 1.00) with warfarin alone compared with warfarin and ASA. Elimination of antiplatelet therapy from the HM II antithrombotic regimen was associated with no significant difference in the composite outcome of bleeding events, thrombotic events, or death, nor the individual components of each end-point.

A Comparison of Self-reported Medication Adherence to Concordance Between Part D Claims and Medication Possession.

OBJECTIVE: Medicare Part D claims indicate medication purchased, but people who are not fully adherent may extend prescription use beyond the interval prescribed. This study assessed concordance between Part D claims and medication possession at a study visit in relation to self-reported medication adherence. MATERIALS AND METHODS: We matched Part D claims for 6 common medications to medications brought to a study visit in 2011-2013 for the Atherosclerosis Risk in Communities study. The combined data consisted of 3027 medication events (claims, medications possessed, or both) for 2099 Atherosclerosis Risk in Communities study participants. Multinomial logistic regression estimated the association of concordance (visit only, Part D only, or both) with self-reported medication adherence while controlling for sociodemographic characteristics, veteran status, and availability under Generic Drug Discount Programs. RESULTS: Relative to participants with high adherence, medication events for participants with low adherence were approximately 25 percentage points less likely to match and more likely to be visit only (P<0.001). The results were similar but smaller in magnitude (approximately 2-3 percentage points) for participants with medium adherence. Compared with females, medication events for male veterans were approximately 11 percentage points less likely to match and more likely to be visit only. Events for medications available through Generic Drug Discount Programs were 3 percentage points more likely to be visit only. CONCLUSIONS: Part D claims were substantially less likely to be concordant with medications possessed at study visit for participants with low self-reported adherence. This result supports the construction of adherence proxies such as proportion days covered using Part D claims.