Ticagrelor for the prevention of ischemic events in patients with prior myocardial infarction and peripheral artery disease

Introduction: Cardiovascular disease (CVD) is the main cause of death in the world. Coronary artery disease (CAD) is the most common form of CVD presentation, but the prevalence of peripheral artery disease (PAD) is increasing. Patients with polyvascular disease comprise a very high-risk population that has been infrequently studied.

Areas covered: The authors review the current evidence of the efficacy and safety of ticagrelor in the setting of acute coronary syndrome and stable patients post-MI with and without PAD and summarize its pharmacokinetics, pharmacodynamics, and regulatory issues.

Expert opinion: Randomized studies showed that ticagrelor is superior to clopidogrel in patients with acute coronary syndromes, and is superior to placebo in the chronic phase (>1 year) post-myocardial infarction. Sub-analyses of these studies suggest that patients with myocardial infarction and PAD, compared to patients without these characteristics, may have greater benefit with ticagrelor. Nonetheless, the global evidence about the role of ticagrelor in patients with myocardial infarction and PAD remains relatively sparse, and a prospective randomized trial testing this hypothesis would be necessary to provide more definite data regarding the efficacy and safety of ticagrelor in this very high-risk population.     

Empiric therapy for secondary peritonitis: a pharmacodynamic analysis of cefepime, ceftazidime, ceftriaxone, imipenem, levofloxacin, piperacillin/tazobactam, and tigecycline using Monte Carlo simulation

BACKGROUND: Inappropriate antibiotic therapy (ie, the selection of an empiric agent without activity against the responsible pathogen) of secondary peritonitis may result in poor patient outcomes. The selection of an appropriate agent can be challenging because of the emerging resistance of target organisms to commonly prescribed antibiotics. OBJECTIVE: The aim of this study was to perform a pharmacodynamic analysis, using recent global surveillance data, of commonly prescribed antibiotic agents and a newer agent, tigecycline, indicated in 2005 for the treatment of complicated intra-abdominal infections, to determine their probability for achieving microbiologic success against aerobic bacteria associated with secondary peritonitis. METHODS: A 2-compartment model was constructed using pharmacokinetic data from critically ill patients and global surveillance data on MIC distributions for microorganisms encountered in secondary peritonitis. A Monte Carlo simulation of the modeled data was performed to determine drug-appropriate pharmacodynamic end points, including free-drug time above the MIC, steady-state concentration above the MIC, and AUC/MIC ratios. A cumulative fraction of response (CFR) against aerobic bacteria involved in secondary peritonitis was calculated for cefepime, ceftazidime, ceftriaxone, imipenem, levofloxacin, pip eracillin/tazobactam, and tigecycline. A CFR > or =90% was considered microbiologic success. The following treatment regimens, administered as 30-minute N infusions, were examined: cefepime 1 and 2 g q12h, ceftazidime 1 and 2 g q8h, ceftriaxone 1 and 2 g q24h, imipenem 500 mg q6h, levofloxacin 750 mg q24h, pip eracillin/tazobactam 3.375 g q6h, and tigecycline 50 mg q12h, after a loading dose of 100 mg. RESULTS: A CFR > or =90% against nonenterococcal bacteria was predicted for imipenem 500 mg q6h (96.8%), cefepime 2 and 1 g q12h (95.3% and 92.4%, respectively), ceftazidime 2 g q8h (94.2%), and piperacillin/tazobactam 3.375 g q6h (91.2%). A CFR of 84.5% was predicted for tigecycline 50 mg q12h. Ceftriaxone and levofloxacin were predicted to have a CFR <80%. When enterococci were included in the model, the predicted CFRs for imipenem, piperacillin/tazobactam, and tigecycline were 93.4%, 88.4%, and 86.7%, respectively. CONCLUSIONS:: MIC distribution and pathogen prevalence strongly influence the likelihood of microbiological success in secondary peritonitis; therefore, decisions regarding empiric therapy should consider local epidemiology. Using current global data, the following regimens are adequate choices if Enterococcus is not targeted: Combination therapy (with metronidazole) using cefepime 1 g or 2 g q12h, or ceftazidime 2 g q8h; or monotherapy with imipenem 500 mg q6h or piperacillin-tazobactam 3.375 g q6h. When Enterococcus is included in the epidemiologic mix, imipenem, piperacillin/tazobactam, and tigecycline all appear to be viable monotherapeutic choices.     

Pharmacodynamic comparisons of levofloxacin, ciprofloxacin, and ampicillin against Streptococcus pneumoniae in an in vitro model of infection

The increasing frequency of penicillin-resistant pneumococcus continues to be of concern throughout the world. Newer fluoroquinolone antibiotics, such as levofloxacin, have shown enhanced in vitro activity against Streptococcus pneumoniae. In this study, the bactericidal characteristics and pharmacodynamic profiles of levofloxacin, ciprofloxacin, and ampicillin against four isolates of S. pneumoniae were compared by using an in vitro model of infection. Standard antibiotic dosing regimens which simulated the pharmacokinetic profile observed in humans were used. Control and treatment models were sampled for bacterial CFU per milliliter over the duration of each 24- or 48-h experiment. In addition, treatment models were sampled for MIC determinations and drug concentration. Regrowth of all isolates as well as an increase in MICs throughout the study period was observed in the ciprofloxacin experiments. A limited amount of regrowth was noted during levofloxacin therapy for one isolate; however, no change in MIC was detected for any isolate. Ampicillin showed rapid and sustained bactericidal activity against all isolates. In this study, ratios of effective fluoroquinolone area under the concentration-time curve (AUC):MIC values ranged from 30 to 55. Levofloxacin, owing to its larger AUC0-24 values, has excellent and sustained activity against different pneumococcal strains superior to that of ciprofloxacin.     

The effects of LED emissions on sternotomy incision repair after myocardial revascularization: a randomized double-blind study with follow-up

This study aimed to analyze the effects of light-emitting diode (LED) therapy on sternotomy pain and healing in patients who underwent coronary artery bypass grafting (CABG). The patients were followed for 6 months after the surgery to determine their dehiscence. This study was conducted with 90 volunteers who electively submitted to CABG. The volunteers were randomly allocated into three different groups of equal size: LED (λ of 640?±?20 nm and spatial average energy fluency of 1.2 J/cm² during hospitalization), placebo, or control. The outcomes assessed were pain when coughing by a visual analog scale (VAS) and the McGill questionnaire and sternotomy healing by clinical assessment and photographical register end interpretation. The LED group had better pain reduction, as indicated by both the VAS and the McGill questionnaire (number of words chosen and pain index) (p?≤?0.05), on days 6 and 8 after hospital discharge compared to the placebo and control groups. One month after surgery, almost no individual mentioned pain when coughing. Three researchers blindly analyzed the incision photographs to determine hyperemia and wound closure, and they found that the LED group had both less hyperemia and less incision bleeding or dehiscence. The LED therapy (640 nm) had an analgesic effect on the sternotomies of patients who underwent CABG, increasing their incision healing and preventing dehiscence.     

“Low-intensity laser therapy effect on the recovery of traumatic spinal cord injury”

Scientific advances have been made to optimize the healing process in spinal cord injury. Studies have been developed to obtain effective treatments in controlling the secondary injury that occurs after spinal cord injury, which substantially changes the prognosis. Low-intensity laser therapy (LILT) has been applied in neuroscience due to its anti-inflammatory effects on biological tissue in the repairing process. Few studies have been made associating LILT to the spinal cord injury. The objective of this study was to investigate the effect of the LILT (GaAlAs laser—780 nm) on the locomotor functional recovery, histomorphometric, and histopathological changes of the spinal cord after moderate traumatic injury in rats (spinal cord injury at T9 and T10). Thirty-one adult Wistar rats were used, which were divided into seven groups: control without surgery (n?=?3), control surgery (n?=?3), laser 6 h after surgery (n?=?5), laser 48 h after surgery (n?=?5), medullar lesion (n?=?5) without phototherapy, medullar lesion?+?laser 6 h after surgery (n?=?5), and medullar lesion?+?laser 48 h after surgery (n?=?5). The assessment of the motor function was performed using Basso, Beattie, and Bresnahan (BBB) scale and adapted Sciatic Functional Index (aSFI). The assessment of urinary dysfunction was clinically performed. After 21 days postoperative, the animals were euthanized for histological and histomorphometric analysis of the spinal cord. The results showed faster motor evolution in rats with spinal contusion treated with LILT, maintenance of the effectiveness of the urinary system, and preservation of nerve tissue in the lesion area, with a notorious inflammation control and increased number of nerve cells and connections. In conclusion, positive effects on spinal cord recovery after moderate traumatic spinal cord injury were shown after LILT.     

Diabetes association with self-reported health,resource utilization,and prognosis post-myocardial infarction

BackgroundDiabetes mellitus (DM) is associated with increased cardiovascular (CV) risk. We compared health‐related quality of life (HRQoL), healthcare resource utilization (HRU), and clinical outcomes of stable post‐myocardial infarction (MI) patients with and without DM.HypothesisIn post‐MI patients, DM is associated with worse HRQoL, increased HRU, and worse clinical outcomes.MethodsThe prospective, observational long‐term risk, clinical management, and healthcare Resource utilization of stable coronary artery disease study obtained data from 8968 patients aged ≥50 years 1 to 3 years post‐MI (369 centers; 25 countries). Patients with ≥1 of the following risk factors were included: age ≥65 years, history of a second MI >1 year before enrollment, multivessel coronary artery disease, creatinine clearance ≥15 and <60 mL/min, and DM treated with medication. Self‐reported health status was assessed at baseline, 1 and 2 years and converted to EQ‐5D scores. The main outcome measures were baseline HRQoL and HRU during follow‐up.ResultsDM at enrollment was 33% (2959 patients, 869 insulin treated). Mean baseline EQ‐5D score (0.86 vs 0.82; P < .0001) was higher; mean number of hospitalizations (0.38 vs 0.50, P < .0001) and mean length of stay (LoS; 9.3 vs 11.5; P = .001) were lower in patients without vs with DM. All‐cause death and the composite of CV death, MI, and stroke were significantly higher in DM patients, with adjusted 2‐year rate ratios of 1.43 (P < .01) and 1.55 (P < .001), respectively.ConclusionsStable post‐MI patients with DM (especially insulin treated) had poorer EQ‐5D scores, higher hospitalization rates and LoS, and worse clinical outcomes vs those without DM. Strategies focusing specifically on this high‐risk population should be developed to improve outcomes.Trial registration ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01866904","term_id":"NCT01866904"}}NCT01866904 (https://clinicaltrials.gov).     

Prospective evaluation comparing the effects of enalapril and losartan in left ventricular remodeling after acute myocardial infarction

Background

Previous studies have compared angiotensin receptor blockers and angiotensin-converting enzyme inhibitors in patients with heart failure, but there are few data about the effect of these drugs regarding left ventricular remodeling after myocardial infarction.

Methods

Fifty-two consecutive patients with first anterior wall myocardial infarction within 24 hours of evolution were randomized to receive enalapril (as much as 20 mg; mean, 14.6 mg), or losartan (as much as 50 mg; mean, 48 mg). Left ventricular ejection fraction and ventricular volumes were analyzed in 2 serial radionuclide ventriculograpies, carried out within 4 days after the infarction (mean, 97.4 ± 114.2 hours) and after 6 months (mean, 177.7 ± 16.7 days). Ventriculographies were analyzed by a single blinded observer. Mainly because of the unexpected large SD values obtained, the power of the study to demonstrate equivalence between the groups was only 15.7%.

Results

The differences obtained between the first and the second ventriculographies, for the enalapril and losartan groups, were: for left ventricular ejection fraction, −0.4% ± 6.6% versus −1.1% ± 5.9% (P = . 67; 95% CI, 2.77-4.23); for final systolic volume, 0.07 ± 7.7 mL/m² versus −0.2 ± 6.1mL/m² (P = . 85; 95% CI, −3.57-4.26); for final diastolic volume −0.7 ± 12.1 mL/m² versus −3.6 - 9.9 mL/m² (P = . 34; 95% CI, −3.22-9.17).

Conclusion

This study, although underpowered, suggests that neither enalapril nor losartan was superior as compared with each other for left ventricular remodeling after myocardial infarction; however, powerful evidence of equivalence was not provided.     

Usefulness of multidetector computed tomography to differentiate between renal cell carcinoma and oncocytoma. A model validation

Objective:The purpose of this study is to validate a multivariable predictive model previously developed to differentiate between renal cell carcinoma (RCC) and oncocytoma using CT parameters.Methods and materials:We included 100 renal lesions with final diagnosis of RCC or oncocytoma studied before surgery with 4-phase multidetector CT (MDCT). We evaluated the characteristics of the tumors and the enhancement patterns at baseline, arterial, nephrographic and excretory MDCT phases.Results:Histopathologically 15 tumors were oncocytomas and 85 RCCs. RCCs were significantly larger (median 4.4 cm vs 2.8 cm, p = 0.006). There were significant differences in nodule attenuation in the excretory phase compared to baseline (median: 31 vs 42, p = 0.015), with RCCs having lower values. Heterogeneous enhancement patterns were also more frequent in RCCs (85.9% vs 60%, p = 0.027).Multivariable analysis showed that the independent predictors of malignancy were the enhancement pattern, with oncocytomas being more homogeneous in the nephrographic phase [Odds Ratio (OR) 0.16 (95% CI 0.03 to 0.75, p = 0.02)], nodule enhancement in the excretory phase compared to baseline, with RCCs showing lower enhancement [OR 0.96 (95% CI 0.93 to 0.99, p = 0.005)], and a size > 4 cm, with RCCs being larger [OR 5.89 (95% CI 1.10 to 31.58), p = 0.038].Conclusion:The multivariable predictive model previously developed which combines different MDCT parameters, including lesion size > 4 cm, lesion enhancement in the excretory phase compared to baseline and enhancement heterogeneity, can be successfully applied to distinguish RCC from oncocytoma.Advances in knowledge:This study confirms that multiparametric assessment using MDCT (including parameters such as size, homogeneity and enhancement differences between the excretory and the baseline phases) can help distinguish between RCCs and oncocytomas. While it is true that this multiparametric predictive model may not always correctly classify renal tumors such as RCC or oncocytoma, it can be used to determine which patients would benefit from pre-surgical biopsy to confirm that the tumor is in fact an oncocytoma, and thereby avoid unnecessary surgical treatments.