TIMI risk index and the benefit of enoxaparin in patients with ST-elevation myocardial infarction

Purpose

The purpose of the study was to evaluate the cause of death, risk of nonfatal complications, and relative outcomes with an enoxaparin versus unfractionated heparin strategy in ST-elevation myocardial infarction stratified using the Thrombolysis in Myocardial Infarction (TIMI) Risk Index (TRI).

Methods

We evaluated 30-day outcomes in 19,941 patients with ST-elevation myocardial infarction treated with fibrinolysis and unfractionated heparin or enoxaparin. Patients were categorized on the basis of prespecified ranges of the TRI [heart rate × (age/10)²/systolic blood pressure].

Results

There was a strongly graded increase in 30-day mortality with increasing TRI (1.2%-20.7%, P <.0001). The proportion of deaths due to mechanical causes (congestive heart failure, shock, and myocardial rupture) increased progressively with the TRI. There also was a significant positively graded association between the TRI and nonfatal heart failure or shock (0.4%-4.4%, P <.0001). In contrast, death resulting from recurrent ischemic events predominated in the lowest TRI group. The relative reduction in death/myocardial infarction with the enoxaparin strategy appeared inversely graded with the TRI. There was a 38% reduction in the lowest risk group (relative risk 0.62, 95% confidence interval 0.45-0.86) and a decrease in the relative benefit of enoxaparin with increasing risk index.

Conclusions

The TRI was a strong predictor of all-cause mortality in a broad population, with a positive association with the risk of death due to mechanical complications and an inverse association with deaths due to recurrent ischemia. The enoxaparin strategy was superior to unfractionated heparin in a majority of patients with ST-elevation myocardial infarction, except for the group at the highest risk for severe mechanical complications, in whom the 2 anticoagulant strategies showed similar results.     

To Evaluate the Effect of Various Surface Treatments on the Shear Bond Strength of Three Different Intraoral Ceramic Repair Systems: An In Vitro Study

Fractures of metal-ceramic restoration pose an esthetic and functional dilemma both for patient and the dentist. Intraoral repair systems eliminate the remake and removal of restoration. Many intraoral repair materials and surface treatments are available to repair intraorally fractured metal-ceramic restoration. Bond strength data of various materials and specific technique used for repair are necessary for predicting the success of a given repair system. This study evaluated the shear bond strength of three different intraoral repair systems for metal-ceramic restorations applied on exposed metal and porcelain surface. One hundred and twenty metal discs (20 mm in diameter × 0.7 mm thick) were fabricated with nickel–chromium alloy (Mealloy, Dentsply, USA). Feldspathic porcelain (Duceram, Degudent, Germany) were applied over one test surface of the discs in the thickness of 1.8 mm followed by conventional firing. The defect, which simulates clinical failures were created in 1/4th area of the metal-ceramic discs. The metal-ceramic discs samples were divided into ceramic substrate (Group I, n = 60) and metal substrate (Group II, n = 60), according to the defect location. Then, samples of ceramic substrate (Group I) and metal substrate (Group II) were subdivided into A, B according to the surface treatments (A; roughening with diamond bur and B; abraded with 50 μ Al₂O₃) and repaired with one of the intraoral repair systems tested (a. Ceramic repair system, Ivoclar Vivadent; b. Clearfil repair system, Kurary, c; Porcelain repair system, 3 M ESPE). All the repaired samples were stored in distilled water at 37 °C for 24 h. After thermocycling at 6–60° C, all the samples were stored at 37 °C for additional 7 days. Shear bond strength of all the samples were calculated by using Universal testing machine. The mean shear bond strength values for the group I (A/B) were as follows: Ceramic repair system (9.47 ± 1.41/14.03 ± 2.54 MPa), Clearfil repair system (14.03 ± 2.32/14.64 ± 2.28 MPa), and Porcelain repair system (14.41 ± 3.96/14.86 ± 3.10 MPa). The mean shear bond strength values for the group II (A/B) were as follows: Ceramic repair system (9.42 ± 1.44/18.61 ± 2.60 MPa), Clearfil repair system (14.44 ± 3.23/14.98 ± 2.73 MPa), and Porcelain repair system (11.86 ± 2.24/13.24 ± 2.72 MPa). Air abrasion with 50 μm aluminum oxide particles is the preferred surface treatment. Porcelain repair system showed the highest shear bond with air abrasion for ceramic substrate and for metal substrate Ceramic repair system showed the highest bond strength with air abrasion as a surface treatment. This study suggest that the three repair systems tested are adequate for intraoral chairside repair of metal-ceramic restoration when air abrasion is used for surface treatment of the substrate (Ceramic repair system, Ivoclar Vivadent, Germany; Clearfil repair system, Kurary, Japan; Porcelain repair system, 3M ESPE, Germany).     

Interval between clinical presentation of necrotizing enterocolitis and bowel perforation in neonates

Objective  

To define the interval between clinical presentation of necrotizing enterocolitis (NEC) and bowel perforation in neonates.     

Topical dosage form of valdecoxib: preparation and pharmacological evaluation

Valdecoxib, a selective COX-2 inhibitor, produces serious side effects when given orally. This has led to its withdrawal. Topical application of valdecoxib was formulated and evaluated for its efficacy and safety. Standard procedures were followed and male Wistar albino rats were used to test the anti-inflammatory effect and effect in hyperalgesic conditions. Ointments, creams, and gels containing valdecoxib 1% (m/m) were prepared. These were tested for physical appearance, pH, spreadability, drug content uniformity, in vitro diffusion. Gel prepared using Carbopol 940 (F-X) was selected after the analysis of the results. Formulation F-X was evaluated for acute skin irritancy, anti-inflammatory effect, optimum effective concentration of valdecoxib, effect on hyperalgesia, inhibition of the granulation tissue formation and anti-arthritic effect. Determination of valdecoxib in test animals plasma and determining the blood clotting time and bleeding time were conducted to study the safety of topical valdecoxib. Valdecoxib gel containing 1% (m/m) of the drug was significantly (p < 0.05) more effective in inhibiting hyperalgesia associated with inflammation, compared to placebo gel, but exhibited significantly (p < 0.05) lower suppression of inflammation than commercial rofecoxib gel. Concentration of valdecoxib used in the preparation minimizes the risk of systemic effects, as shown by the analysis of rat plasma for the presence of valdecoxib; hence, this may be the alternative to oral preparations. The bleeding and clotting time showed no significant difference before and after application of F-X.     

Acute Decline in Renal Function,Inflammation, and Cardiovascular Risk after an Acute Coronary Syndrome

Background and objectives: Chronic kidney disease is associated with a higher risk of cardiovascular outcomes. The prognostic significance of worsening renal function has also been shown in various cohorts of cardiac disease; however, the predictors of worsening renal function and the contribution of inflammation remains to be established.Design, setting, participants, & measurements: Worsening renal function was defined as a 25% or more decrease in estimated GFR (eGFR) over a 1-mo period in patients after a non-ST or ST elevation acute coronary syndromes participating in the Aggrastat-to-Zocor Trial; this occurred in 5% of the 3795 participants.Results: A baseline C-reactive protein (CRP) in the fourth quartile was a significant predictor of developing worsening renal function (odds ratio, 2.48; 95% confidence interval, 1.49, 4.14). After adjusting for baseline CRP and eGFR, worsening renal function remained a strong multivariate predictor for the combined cardiovascular composite of CV death, recurrent myocardial infarction (MI), heart failure or stroke (hazard ratio, 1.6; 95% confidence interval, 1.1, 2.3).Conclusions: Patients with an early decline in renal function after an acute coronary syndrome are at a significant increased risk for recurrent cardiovascular events. CRP is an independent predictor for subsequent decline in renal function and reinforces the idea that inflammation may be related to the pathophysiology of progressive renal disease.Impaired renal function has consistently been shown to be an independent risk factor for cardiovascular outcomes across a broad spectrum of patients including population-based studies of patients with cardiovascular disease (1,2), acute coronary syndromes (3–6), chronic heart failure with either impaired or preserved ventricular systolic function (7), and after coronary artery bypass grafting (8). Worsening renal function (WRF), defined by small increases in creatinine or decreases in GFR, has also been independently associated with adverse cardiovascular outcomes and mortality in patients after an acute MI (9), cardiac surgery (10,11), and in patients with heart failure (12–14).Serum C-reactive protein (CRP), a marker of inflammation, has been associated with WRF in a population of nondiabetics (15), as well as in those after an MI (15,16). The predictors and prognostic significance of WRF in a cohort of patients after an acute coronary syndrome (ACS) is not well defined. Furthermore, the contribution of inflammatory markers to WRF in this cohort is unknown. We analyzed subjects from the phase Z of the A-Z trial (Early Intensive versus Delayed Conservative Simvastatin Strategy in Patients with Acute Coronary Syndromes), who had both measurements of serum creatinine and thus estimates of GFR (eGFR), at baseline and 1 mo. We have previously reported that both baseline CRP and eGFR were important prognostic markers after an ACS and that the increased cardiovascular hazard associated with a reduction in eGFR was independent and additive to baseline markers of inflammation (6). The objectives of this subsequent analysis was to determine clinical factors associated with an early decline in eGFR after an ACS and second to evaluate the cardiovascular prognostic importance of an early decline in eGFR in this patient population.