Use Of Enzyme Inhibitors Research Articles

Advanced Approaches of Bioactive Peptide Molecules and Protein Drug Delivery Systems

Despite the fact that protein and peptide therapeutics are widely employed in the treatment of various diseases, their delivery is posing an unembellished challenge to the scientists. It was discovered that delivery of these therapeutic systems through oral route is easy with high patient compliance. However, proteolytic degradation and absorption through the mucosal epithelium are the barriers in this route. These issues can be minimized by the use of enzyme inhibitors, absorption enhancers, different carrier systems or either by direct modification. In the process of investigation, it was found that transdermal route is not posing any challenges of enzymatic degradation, but, still absorption is the limitation as the outer layer of skin acts as a barrier. To suppress the effect of the barrier and increase the rate of the absorption, various advanced technologies were developed, namely, microneedle technology, iontophoresis, electroporation, sonophoresis and biochemical enhancement. Indeed, even these molecules are targeted to the cells with the use of cell-penetrating peptides. In this review, delivery of the peptide and protein therapeutics using oral, transdermal and other routes is discussed in detail.

Is prescribing by PAs and NPs comparable to physician prescribing?

PAs and NPs have broad prescribing authority in the United States, yet little is known about how the quality of their prescribing practices compares with that of physicians. The quality of prescribing practices of physicians, PAs, and NPs was investigated through a serial cross-sectional analysis of the 2006-2012 National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS). Ambulatory care services in physician offices, hospital EDs, and outpatient departments were evaluated using a nationally representative sample of patient visits to physicians, PAs, and NPs. Main outcome measures were 13 validated outpatient quality indicators focused on pharmacologic management of chronic diseases and appropriate medication use. The study sampled 701,499 patient visits during the study period, representing about 8.3 billion visits nationwide. Physicians were the primary provider for 96.8% of all outpatient visits examined; PAs and NPs each accounted for 1.6% of these visits. The proportion of eligible visits in which quality standards were met ranged from 34.1% (angiotensin-converting enzyme inhibitor use for patients with heart failure) to 89.5% (avoidance of inappropriate medications in older adults). The median overall performance across all indicators was 58.7%. On unadjusted analyses, differences in quality of care between PAs, NPs, and physicians for each indicator did not consistently favor one practitioner type over others. After adjustment for potentially confounding patient and provider characteristics, the quality of prescribing by PAs and NPs was similar to the care delivered by physicians for 10 of the 13 indicators evaluated, and no consistent directional association was found between provider type and indicator fulfillment for the remaining measures. Although significant shortfalls exist in the quality of ambulatory prescribing across all practitioner types, the quality of care delivered by PAs, NPs, and physicians was generally comparable.1.

Snapshot evaluation of heart failure in Turkey: Baseline characteristics of SELFIE-TR

Heart failure (HF) is an important health issue of the 21st century and the prevalence in Turkey has been reported as 2.9%. A national profile, frequency data, characteristics of different phenotypes, and risk factors have not yet been well established. The Snapshot Evaluation of Heart Failure Patients in Turkey (SELFIE-TR) was an analysis of a representative sample of HF patients from Turkey. A total of 23 centers with at least 2 cardiologists from the 12 NUTS-1 regions of Turkey were invited to participate in the research. The contributing centers shared the data of a consecutive enrollment of HF patients, as confirmed by an investigator, on a pre-selected day of each week for the month of October or November of 2015. The mean age of the entire cohort was 63.3+-13.3 years (male/female ratio: 751/303, 71.3%/28.7%). There were 712 acute HF patients and 342 chronic HF patients. The total number of HF patients with reduced ejection fraction (HFrEF), heart failure with mid-range ejection fraction, and heart failure with preserved ejection fraction was 801 (75%), 176 (16.7%), and 77 (7.3%), respectively. The patients with chronic HF were younger than those with acute HF (61.1+-13.3 years vs 67.9+-12.1 years; p<0.001). Among the whole cohort, hypertension was observed in 46%, diabetes mellitus was present in 27.5%, chronic obstructive pulmonary disease was present in 12.8%, and previous myocardial infarction was noted in 45.2%. In patients with HFrEF, the use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, a beta blocker, or a mineralocorticoid receptor antagonist was noted in 74.7%, 89.7%, and 60.9%, respectively. The SELFIE-TR findings provide important insight, since it is the first study to make a snapshot of HF patients in our country. These data may help to create standardized prevention and treatment strategies.

Use of ACE-inhibitors and Quality of Life in an Older Population.

Improved ability to treat chronic diseases have increased the interest in measuring health-related quality of life (HRQoL) in older adults. Hypertension and heart failure have been associated with decreased HRQoL. The aim of this study was to assess the association between health-related quality of life and use of angiotensin converting enzyme inhibitors in unselected community-dwelling elderly. We analyzed data of all 387 subjects aged 75+ living in a rural Italian town, without exclusion criteria. HRQoL was assessed using the Health Utility Index Mark 3, which allows formal cost-effectiveness calculations. The association of the HRQoL score with use of ACE-I was analyzed by multivariable linear and logistic regression. The median HUI3 score was 0.31, and 186 participants (48%) reported a score above the median value. Use of ACE-I was reported by 34 (9%) participants, and confirmed by general practitioners. Use of these agents was associated with significantly better HRQoL (B=.16, 95% CI=.02 - .30; P=.025). Also, use of ACE-I was associated with increased probability of better HRQoL in logistic regression (OR=2.83; 95% CI=1.03 - 7.78; P=.044) after adjusting. No associations were found between the HRQoL score and use of calcium antagonists or beta-blockers. Use of ACE-I, but not of other antihypertensives, is associated with better HRQoL among community-dwelling older adults. ACE-inhibitors might therefore present with the best cost-effectiveness ratio for the treatment of older populations.

Daily Lisinopril vs Placebo for Prevention of Chemoradiation-Induced Pulmonary Distress in Patients With Lung Cancer (Alliance MC1221): A Pilot Double-Blind Randomized Trial

Chemoradiation (CRT) is an integral treatment modality for patients with locally advanced lung cancer. It has been hypothesized that current use of an angiotensin-converting enzyme inhibitor during CRT may be protective for treatment-related lung damage and pneumonitis. We conducted a pilot, double-blind, placebo-controlled, randomized trial. Study-eligible patients receiving curative thoracic radiation therapy (RT) were randomly assigned to 20mg of lisinopril or placebo once daily during and up to 3months after RT. All patients received concurrent chemotherapy. The primary endpoint was adverse event profiling. Multiple patient-reported outcome (PRO) surveys, including the Lung Cancer Symptom Scale, Function Assessment of Cancer Therapy-Lung, and the European Organisation for Research and Treatment of Cancer Lung Cancer Questionnaire, were applied with a symptom experience questionnaire. Exploratory comparative statistics were used to detect differences between arms with χ2 and Kruskal-Wallis testing. Five institutions enrolled 23 patients. However, accrual was less than expected. Eleven and 12 patients were in the placebo and lisinopril arms, respectively (mean age, 63.5years; male, 62%). Baseline characteristics were balanced. Eighteen patients (86%) were former or current smokers. The primary endpoint was met; neither arm had grade 3 or higher hypotension, acute kidney injury, allergic reaction (medication-induced cough), or anaphylaxis (medication-related angioedema). Few PRO measures suggested that compared with the placebo arm, patients receiving lisinopril had less cough, less shortness of breath, fewer symptoms from lung cancer, less dyspnea with both walking and climbing stairs, and better overall quality of life (for all, P<.05). Although underpowered because of low accrual, our results suggest that there was a clinical signal for safety-and possibly beneficial by limited PRO measures-in concurrently administering lisinopril during thoracic CRT to mitigate or prevent RT-induced pulmonary distress. Our results showed that a definitive, larger-scale, randomized phase 3 trial is needed in the future.

Effect of 2 Clinical Decision Support Strategies on Chronic Kidney Disease Outcomes in Primary Care

Information is needed about optimal strategies to improve evidence-based treatment of chronic kidney disease (CKD) in primary care. To determine whether a multimodal intervention delays annualized loss of estimated glomerular filtration rate (eGFR) in stages 3 and 4 CKD. This pragmatic cluster randomized clinical trial enrolled 42 primary care practices located in nonhospital settings with electronic health record systems. Practices were recruited through the American Academy of Family Physicians National Research Network. The study was conducted January 2013 through January 2016. Practices were randomized at the organization level to either the clinical decision support (CDS) plus practice facilitation (PF) group (n = 25) or CDS group (n = 17) using covariate constrained randomization. Both groups received point-of-care CDS to prompt screening, diagnosis, and treatment of CKD; the intervention group also received PF based on the 9-point TRANSLATE model (target, use point-of-care reminder systems, get administrative buy-in, network information systems using registries, site coordination, local physician champion, audit and feedback, team approach, and education). The primary outcome measure was eGFR over time. Secondary outcome measures were systolic blood pressure over time, change in hemoglobin A1c (HbA1c) over time, avoidance of nonsteroidal anti-inflammatory medications, use of angiotensin converting enzyme inhibitor or angiotensin-renin blocker medication, early recognition and diagnosis of CKD, blood pressure control, and smoking cessation. In this cluster randomized trial of 30 primary care practices comprising 6699 patients, there were 1685 patients in the control group (10 practices) and 5014 patients in the intervention group (20 practices). The final sample of practices differed from the original set of randomized practices owing to dropout. Patients in the practices were similar at baseline for age (mean [SD], 71.3 [9.6] years), sex (2716 male [40.5%]), and eGFR. There was a significant difference in eGFR slopes for patients in the intervention vs control group practices. The mean (SE) annualized loss of eGFR was 0.95 (0.19) in the control group in propensity-adjusted longitudinal analyses and 0.01 (0.12) in the intervention group (mean [SE] difference in slopes, 0.93 [0.23]; P < .001). Among patients with HbA1c measures, slopes differed significantly for patients in intervention vs control practices, with a mean (SE) annualized increase of 0.14 (0.03) in HbA1c for patients in control practices and a mean (SE) decline of 0.009 (0.02) for patients in intervention practices. There was a significant difference in HbA1c slopes for patients in the intervention compared with control group practices (control vs intervention, -0.14; P < .001), but no difference in the other secondary outcomes. A multimodal intervention in primary care, based on the TRANSLATE model, slowed annualized loss of eGFR. This study had several important strengths, weaknesses, and lessons learned regarding the implementation of pragmatic interventions in primary care to improve CKD outcomes. ClinicalTrials.gov Identifier: NCT01767883.

Angiotensin converting enzyme inhibitors and risk of lung cancer: population based cohort study

ObjectiveTo determine whether the use of angiotensin converting enzyme inhibitors (ACEIs), compared with use of angiotensin receptor blockers, is associated with an increased risk of lung cancer.DesignPopulation based cohort study.SettingUnited...

Amyloidoza łańcuchów lekkich immunoglobulin z punktu widzenia kardiologa

Light-chain amyloidosis (amyloidosis AL) is diagnosed in approx. 70% of patients with cardiac amyloidosis. This type of amyloidosis has the worst prognosis, especially if the diagnosis is made in advanced stages. The majority of patients are referred to a cardiologist, but unfortunately only every fifth of them has the proper diagnosis. Therefore, strategies promoting early diagnosis are important. One of them is the measurement of serum free light chains concentration in every patient with heart failure with preserved ejection fraction. The acknowledgement of free light chains (FLCs) cardiotoxicity rendered the picture of AL amyloidosis from infiltrative cardiomyopathy into a toxic one. Best improvement in regard to heart failure is achieved upon hematological treatment resulting in decrease of FLCs concentration. Therefore, cardiological treatment is rather a supportive therapy. The role of cardiologist is the rapid diagnosis of the disease and referral of the patient to the hematologist. The standard heart failure treatment encompassing use of beta-blockers and angiotensin converting enzyme inhibitors aggravates orthostatic hypotension and congestion. Instead, up-to-date hematological treatment improves the prognosis of AL amyloidosis markedly, as long as early diagnosis is made.

Use of Antihypertensive Agents and Association With Risk of Adverse Outcomes in Chronic Kidney Disease: Focus on Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers.

BackgroundOur objective was to determine patterns of antihypertensive agent use by stage of chronic kidney disease (CKD) and to evaluate the association between different classes of antihypertensive agents with nonrenal outcomes, especially in advanced CKD.Methods and ResultsWe studied 3939 participants of the CRIC (Chronic Renal Insufficiency Cohort) study. Predictors were time‐dependent angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker , β‐blocker, and calcium channel blocker use (versus nonuse of agents in each class). Outcomes were adjudicated heart failure events or death. Adjusted Cox models were used to determine the association between predictors and outcomes. We also examined whether the associations differed based on the severity of CKD (early [stage 2–3 CKD] versus advanced disease [stage 4–5 CKD]). During median follow‐up of 7.5 years, renin‐angiotensin‐aldosterone system inhibitor use plateaued during CKD stage 3 (75%) and declined to 37% by stage 5, while β‐blocker, calcium channel blocker, and diuretic use increased steadily with advancing CKD. Renin‐angiotensin‐aldosterone system inhibitor use was associated with lower risk of heart failure (hazard ratio, 0.79; 95% confidence interval, 0.67–0.97) and death (hazard ratio, 0.78; 95% confidence interval, 0.67–0.90), regardless of severity of CKD. Calcium channel blocker use was not associated with risk of heart failure or death, regardless of the severity of CKD. β‐Blocker use was associated with higher risk of heart failure (hazard ratio, 1.62; 95% confidence interval, 1.29–2.04) and death (hazard ratio, 1.22; 95% confidence interval, 1.03–1.43), especially during early CKD (P<0.05 for interaction).ConclusionsAngiotensin‐converting enzyme inhibitor and angiotensin receptor blocker use decreased, while use of other agents increased with advancing CKD. Use of agents besides angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers may be associated with suboptimal outcomes in patients with CKD.

The Difference between the Therapeutic Effects of Thiamine &amp; ACEI as Therapeutic Agents for the Control of Blood Glucose and ABP in Type II Diabetic Rats, A Comparative Study

AbstractBackground: Thiamine is a vitamin with a widespread physiological functions and therapeutic effects. Its beneficial effects in different diseases conditions is the subject area of multiple recent researches. Especially in chronic diseases as diabetes and hypertension.Aim of the Study: Test and compare the possible protective effects of angiotensin converting enzyme inhibitor and thiamine in type 2 diabetic rats.Patients and Methods: A total of 55 male albino rats were used in this study weighing 150-200 grams. The animals were housed in wire mesh cages at room temperature, with normal light dark cycle. They were fed the commercial rat chew diet and had free access to water. These rats were divided into the following groups: Group 1: Control group, Group 2: Type 2 diabetic rats, Group 3: Type 2 diabetic nephropathy rats, Group 4: Lisinopril-treated type 2 diabetic nephropathy rats, Group 5: Thiamine mononitrate-treated type 2 diabetic neph-ropathy rats. Blood samples were collected for measurement of fasting blood glucose, fasting blood insulin. Homeostasis model assessment of insulin resistance was calculated. Systolic blood pressure and diastolic blood pressure were also measured. Nuclear factor kappa B gene expression was estimated.Results: Treatment with angiotensin converting enzyme inhibitor reduced fasting blood glucose, fasting blood insulin, nuclear factor kappa B gene expression, systolic blood pressure and diastolic blood pressure. While treatment with thiamine mononitrate reduced fasting blood glucose and systolic blood pressure.Conclusion: The use of angiotensin converting enzyme inhibitor and thiamine in the treatment of type 2 diabetes significantly improved the ABP and the diabetic condition in type 2 diabetes mellitus. ACE inhibitors also inhibits the inflammatory cascade.

Anti-Hypertensive Medication Use, Soluble Receptor for Glycation End Products and Risk of Pancreatic Cancer in the Women's Health Initiative Study.

Pancreatic cancer is the fourth leading cause of cancer death. Soluble receptor for glycation end products (sRAGE), which is modulated by anti-hypertensive (HT) medications, has been inversely associated with pancreatic cancer. However, the association between commonly used anti-HT medications and risk of pancreatic cancer is unknown. A total of 145,551 postmenopausal women from the Women Health Initiative (WHI) Study were included in analysis. Use of angiotensin converting enzyme inhibitors (ACEi), β-blockers, calcium channel blockers (CCBs) and diuretics was ascertained at baseline (1993–1998). Baseline sRAGE levels were measured among a subset of 2104 participants using an immunoassay. Multivariable Cox proportional hazard regression model was performed to estimate hazard ratios (HRs) and its 95% confidence intervals (CIs) for pancreatic cancer in association with anti-HT medications. Increased risk of pancreatic cancer was found among users of short-acting CCB (HR = 1.66, 95% CI: 1.20–2.28) and long-term (≥3 years) users of short-acting CCB (HR = 2.07, 95% CI: 1.42–3.02) compared to users of other anti-HT medications. Average sRAGE levels were lower in short-acting CCB users than users of other anti-HT medications (1173 versus 1454 pg/mL, p = 0.038). Non-statistically significant reduced risk of pancreatic cancer was found among users of β-blockers (HR = 0.80, 95% CI: 0.60–1.07). Average sRAGE levels were higher in β-blockers users than users of other anti-HT medications (1692 versus 1454 pg/mL, p > 0.05). Future studies are warranted to confirm these findings and elucidate potential mechanisms by which anti-HT medications influence development of pancreatic cancer.

Pathophysiological Insights into Persistent Hyponatremia after LVAD Implantation

Background Persistent hyponatremia after LVAD implantation is not uncommon in patients with end-stage heart failure (HF) and maybe associated with adverse outcomes. The etiology of hyponatremia in HF patients is multifactorial including - low cardiac output state, volume expansion, impaired free water excretion due to renal insufficiency and use of loop diuretics. It is generally thought that with restoration of hemodynamics hyponatremia would resolve after LVAD implantation. We sought to determine the etiology of persistent hyponatremia after LVAD implantation. Methods We performed a retrospective analysis of patients with end-stage HF who received a continuous-flow LVAD and subsequently underwent right heart catheterization (RHC) to assess invasive hemodynamics and for speed optimization. Data was collected concurrently on invasive hemodynamics, medication usage and basic metabolic panel. Hyponatremia was defined as serum sodium level 12 mmHg, volume depletion defined by RAP 0.75 (moderate) and >1.0 (severe), partially unloaded left ventricle (LV) defined by PCWP > 15, use of angiotensin converter enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), use of loop diuretics and renal function measured by estimated glomerular filtration rate (GFR). Each of the factors were compared between patients with hyponatremia and normal sodium levels. Results We included 143 patients in our study. RHC was performed within 6 months from LVAD implantation in 70% of the population, the median time was 199 days. Patients with hyponatremia had a mean sodium of 130.5 mEq/L compared to 139.8 mEq/L in patients with normonatremia, p-value table 1 ). One-year mortality and all-cause readmissions (from time of RHC) were both higher in the hyponatremia group, p-values of 0.012 and 0.023 respectively. Discussion Persistent hyponatremia after LVAD implantation does not appear to be related to low cardiac output state, volume expansion or depletion, RV dysfunction, use of ACEI or ARBs, loop diuretics or renal function. Hyponatremia may be an independent marker of adverse outcomes after LVAD implantation.

Effect of Anti-Hypertensive Medication History on Arteriovenous Fistula Maturation Outcomes

Background: The arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. However, approximately half of AVFs fail to mature. The use of angiotensin converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs) exerts favorable endothelial effects and may promote AVF maturation. We tested associations of ACE-I and ARBs, CCBs, beta-blockers, and diuretics with the maturation of newly created AVFs. Methods: We evaluated 602 participants from the Hemodialysis Fistula Maturation Study, a multi-center, prospective cohort study of AVF maturation. We ascertained the use of each medication class within 45 days of AVF creation surgery. We defined maturation outcomes by clinical use within 9 months of surgery or 4 weeks of initiating hemodialysis. Results: Unassisted AVF maturation failure without intervention occurred in 54.0% of participants, and overall AVF maturation failure (with or without intervention) occurred in 30.1%. After covariate adjustment, CCB use was associated with a 25% lower risk of overall AVF maturation failure (95% CI 3%–41% lower) but a non-significant 10% lower risk of unassisted maturation failure (95% CI 23% lower to 5% higher). ACE-I/ARB, beta-blocker, and diuretic use was not significantly associated with AVF maturation outcomes. None of the antihypertensive medication classes were associated with changes in AVF diameter or blood flow over 6 weeks following surgery. Conclusions: CCB use may be associated with a lower risk of overall AVF maturation failure. Further studies are needed to determine whether CCBs might play a causal role in improving AVF maturation outcomes.

PO-395 Mechanistic investigation of epigenetic modifications induced by metabolic changes in AML

IntroductionAcute Myeloid Leukaemia is the most common and aggressive adult leukaemia with a high frequency of relapse and mortality. This is likely due to the failure to eliminate the malignant stem like population (LSCs) composed by low cycling cells that give rise to highly proliferating blast type progenitors. Although the currently available chemotherapeutic agents efficiently eradicate blasts, LSCs can be retained and cause relapse. Therefore, new therapeutic strategies aimed to specifically eradicate them is urgently needed.These insights led to an increasing interest in understanding the molecular mechanisms governing LSCs biology. Along this line, recent reports (Raffel et al. Nature 2017) highlight the crucial role of Branched Chain Amino Acid (BCAA) catabolism in LSCs. Indeed, BCAA Transaminase 1 (BCAT1) is highly expressed in LSCs and led to reduction of alpha-ketoglutarate (aKG) levels, with consequent impairment of aKG-dependent dioxygenases activity, such as TET1/2, and increase in DNA methylation, resembling AML with TET or an IDH mutation. Moreover, BCAT1 overexpression is associated with poor overall survival in patients which have no TET or IDH mutation.However, aKG is also a cofactor of histone-demethylases and it remains unclear whether BCAT1 also affects these enzymes, which regulate chromatin structure and activity.Material and methodsGenome wide approaches (i.e. ChIPseq for specific histone marks, ATACseq, RNAseq, DNA methylation) are used to mechanistically dissect the connexion between BCAT1 mediated metabolic changes and alterations in the chromatin landscape of AML cell lines (HL-60, SKM1-MOLM-13) and LSCs,Results and discussionsIn order to understand if BCAT1 is controlling the chromatin structure, the transcription factor binding and the histone methylation status, we performed H3K27ac-H3K27me3-H3K4me1-H3K4me3 ChIPseq experiments and ATACseq on control and BCAT overexpressing cells. Despite the global DNA methylation changes observed in BCAT1 overexpressing cells,Raffel et al., Nature 2017 ChIPseq and ATACseq analyses did not show a global change in chromatin structure and modifications. Nonetheless, differences in specific loci were identified after BCAT1 overexpression suggesting a more complicated scenario and opening the road for further analyses.ConclusionThis work will provide rationale for the use of metabolic enzyme inhibitors (alone or in combination with epigenetic inhibitors) as a therapeutic approach in AML and other solid BCAT1 overexpressing tumour entities.

Angiotensin converting enzyme inhibitors and interstage failure in infants with hypoplastic left heart syndrome.

Angiotensin converting enzyme inhibitors are commonly prescribed medications after the Norwood procedure. There are little data that can be used to determine if angiotensin converting enzyme inhibitors improve interstage outcomes in children with single ventricle defects. The objective of this study was to investigate the relationship between angiotensin converting enzyme inhibitors and interstage failure among infants born with hypoplastic left heart syndrome. We conducted a retrospective cohort study using data from the National Pediatric Cardiology Quality Improvement Collaborative database (collected between 2008 and 2015). We used logistic regression models to assess the exposure-outcome associations and propensity score matching to account for differences in baseline patient characteristics associated with use of angiotensin converting enzyme inhibitors. A total of 1487 neonates participated in the study. Thirty-nine percent of patients were prescribed angiotensin converting enzyme inhibitors after the Norwood procedure; 11% experienced interstage failure (death, heart transplantation, and not being a candidate for the second-stage surgery). Before propensity score matching, patients receiving angiotensin converting enzyme inhibitors were significantly more likely to experience interstage failure, compared to patients not on angiotensin converting enzyme inhibitors (OR = 1.44; 95% CI: 1.04, 1.99; P = 0.03). Although there was an increased odds of interstage failure among patients receiving angiotensin converting enzyme inhibitors compared to patients not receiving angiotensin converting enzyme inhibitors in the propensity score-matched cohort, this association was not significantly different (adjusted OR = 1.29; 95% CI: 0.88, 1.95; P = 0.18). Angiotensin converting enzyme inhibitor therapy did not demonstrate a beneficial effect on interstage failure among infants with hypoplastic left heart syndrome, even when patient characteristics associated with the use of angiotensin converting enzyme inhibitors were considered.

Unexpected difficult airway management due to the use of ACE inhibitors

Angioedema induced by the use of angiotensin converting enzyme (ACE) inhibitors is an uncommon but life-threatening complication, especially when the airway is affected, creating unexpected difficult airway management. A prompt differential diagnosis with anaphylactic shock is critical, given that adrenaline treatment does not improve angioedema. We report a case of angioedema induced by ACE inhibitor following in-hospital administration of captopril, with almost impossible intubation, and secondary aspiration during airway management. Angioedema was erroneously treated, because it was mistakenly considered to be an anaphylactic reaction, and it could have ended in death.

Severe Infrarenal Atheroma Load in Open Aortic Aneurysm Repair Is Not a Risk Factor for Postoperative Acute Kidney Injury

Acute kidney injury (AKI) after open aortic repair is subject to multiple patient- and operation-related variables. Hostile neck morphology in open aneurysm repair is thought to contribute to this AKI risk postoperatively. The aim of this study was to evaluate if large neck atheroma is a possible risk factor in the postoperative development of AKI. Retrospectively 137 patients were evaluated for neck atheroma and AKI incidence. Atheroma load measurements were performed by 2 different techniques. Results were compared, and secondly a univariate analysis was performed for multiple additional risk factors regarding AKI occurrence. Significant (>30%) neck atheroma was not associated with a higher risk for developing AKI (odds ratio [OR]: 1.81; 95% confidence intervals: 0.74-4.44). Overall incidence of AKI based upon Acute Kidney Injury Network criteria was 19.7%. In univariate analysis coronary artery disease and the presence of a renal artery stenosis were both significantly associated with AKI (OR: 2.38, 3.31, respectively) as well as the use of B-blockers and angiotensin converting enzyme inhibitors (OR 3.05, 2.48, respectively). Cross-clamping in case of significant neck atheroma during open aortic aneurysm repair is not associated with increased risk of AKI. Defining high-risk patients based on additional risk factors must be a part of preoperative patient selection.

Efficacy of Traditional Chinese Medicine in patients with acute myocardial infarction suffering from diabetes mellitus

OBJECTIVETo investigate the “real world” effectiveness of Traditional Chinese Medicine (TCM) in patients with acute myocardial infarction suffering from diabetes mellitus (AMI+DM patients). METHODSThis was a retrospective cohort study. During hospitalization, the “exposure group” was defined as patients who had a TCM injection for ≥ 7 d. During follow-up, the definition of the exposure group was application of a Chinese patent medicine or decoction of Chinese medicine for ≥ 28 d. General information (age, sex, contact details), TCM use and endpoint events of AMI + DM patients during hospitalization and follow-up were collected. The correlation between TCM and the end-point events of AMI + DM patients was analyzed using a multiple logistic regression method. RESULTSA total of 479 AMI + DM patients were enrolled and 345 cases were followed up. During hospitalization, TCM, age, hypertension and use of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) were associated with cardiac death. During follow-up, TCM was associated with cardiac death. TCM was a relevant factor for a composite endpoint of re-infarction and stroke. TCM, anti-thrombotic therapy and lipid-lowering therapy were related to acute heart failure. TCM, anti-thrombotic therapy, anti-MI therapy and ACEI/ARB use exhibited a strong correlation with re-hospitalization due to cardiovascular disease. CONCLUSIONTCM reduced the prevalence of cardiac death during hospitalization, and cardiac death, a composite endpoint of re-infarction and stroke, acute heart failure and re-hospitalization due to cardiovascular disease during follow-up.

CLINICAL DETERMINANTS OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS/ANGIOTENSIN RECEPTOR BLOCKERS USE IN AN EARLY PHASE AFTER ACUTE HEART FAILURE HOSPITALIZATION

Objective: To investigate which clinical determinants predict the use of angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) in an early phase after acute heart failure (AHF) hospitalization. Design and method: A prospective two-centre observational cohort study enrolled 1433 dyspnoeic patients consecutively admitted to an emergency department. AHF was the cause of acute dyspnoea in 635 patients (44.3%). The mean age was 69.7 ± 12.1; 42% were female. Medication follow up data for 574 and 567 AHF patients were available 1 and 3 months after discharge, respectively. Predictors for ACEi/ARB use were identified by an univariate analysis and multivariate stepwise analysis. Results: The mean systolic blood pressure (SBP) of AHF (n = 635) patients was 139.5 ± 27.8; 59% had a SBP > = 140 mmHg. ACEi/ARB were prescribed in 59.7%, 47.9% and 46.9% of patients at discharge as well as 1 and 3 months after discharge, respectively. SBP of 140 mmHg was identified as a threshold to receive ACEi/ARB at discharge using ROC analysis (area under the curve 0.595). Univariate and independent predictors of ACEi/ARB use are presented in Table 1.Conclusions: Less than half of patients received ACEi/ARB 1 and 3 months after discharge for AHF. SBP, history of hypertension and chronic kidney disease were identified as independent predictors of treatment with ACEi/ARB in an early phase after AHF hospitalization.

COMPARISON OF HOSPITALIZED AND AMBULATORY HYPERTENSIVE PATIENTS’ PHARMACOTHERAPY IN THE PERSPECTIVE OF POLYPRAGMASY

Objective: Cardiovascular diseases cause 1/3 of all deaths, thus they represent a leading global cause of mortality. In Romania, 40% of the adult population is hypertensive, and only three out of seven, among the patients that are being treated, are getting the appropriate pharmacotherapy. Our goal is the evaluation and comparison of the pharmacotherapy of adult hospitalized and ambulatory hypertensive population. Design and method: The cross-sectional, observational, prospective, pharmaco-epidemiological study targets the observation, analysis and comparison of pharmacotherapy of two groups of patients (hospitalized and ambulant patients), in the perspective of polypragmasy and self-medication, if it occured. Results: The average age of hospitalized patients was 70.65+/−4.95 (SD) years, and 68.39+/−10.49 (SD) years of the outpatients. A statistically significant difference has been found regarding the gender rate in the two groups of patients (p = 0.0474), whereas 59% of the hospitalized patients were women compared to only 45% of the outpatients. A statistically significant difference has been found between the two groups’ angiotensin convertase enzyme inhibitors (ACEI) use: 44.86% in case of inpatients and 70.52% in case of outpatients (p = 0.0006), and also regarding the usage of beta-receptor blockers (63.83% hospitalized vs. 44.5% ambulatory). The incidence of polypragmasy of inpatients was 85.12% and in 4.26% of the cases a combination of more than ten drugs occurred. Compared to the ambulatory patients, where the incidence rate of polypragmasy was 61.84% and 6.93% of them used more than ten different drugs daily, the difference is statistically significant (p = 0.0004). Conclusions: Female hypertensive patients are more likely to be hospitalized due to their complications. Beta-receptor blockers are more frequently used in hospitalized cases, and ACEI are more widespread in case of ambulatory patients. A possible explanation includes that the use of ACEI is safer and produce less side effects than beta-blockers, which are tested on hospitalized patients before the long-term introduction in their therapy. Polypragmasy is common in both groups of patients, but it seems to occur at higher rates in case of inpatients, due to the more intense monitoring possibilities.