Management of an Oral Ingestion of Transdermal Fentanyl Patches: A Case Report and Literature Review

Purpose. Fentanyl is available as a transdermal system for the treatment of chronic pain in opioid-tolerant patients; however, it carries a black box warning due to both the potency of the product and the potential for abuse. In this report, we describe a case of transbuccal and gastrointestinal ingestion of fentanyl patches and the management of such ingestion. Summary. A 32-year-old man was brought to the emergency department (ED) via emergency medical services for toxic ingestion and suicide attempt. The patient chewed and ingested two illegally purchased transdermal fentanyl patches. In the ED, the patient was obtunded, dizzy and drowsy. Initial vital signs showed the patient to be afebrile and normotensive with a heart rate of 63, respiratory rate of 16, and oxygen saturation of 100% on 2 liters nasal cannula after administration of 2 milligrams of intravenous naloxone. The patient was treated with whole bowel irrigation and continuous intravenous naloxone infusion for approximately 48 hours without complications. Conclusion. Despite numerous case reports describing oral ingestion of fentanyl patches, information on the management of such intoxication is lacking. We report successful management of such a case utilizing whole bowel irrigation along with intravenous push and continuous infusion naloxone

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Comparison Of Cefazolin Versus Oxacillin For Treatment Of Complicated Bacteremia Caused By Methicillin-Susceptible Staphylococcus Aureus

Contrary to prior case reports that described occasional clinical failures with cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infections, recent studies have demonstrated no difference in outcomes between cefazolin and antistaphylococcal penicillins for the treatment of MSSA bacteremia. While promising, these studies described low frequencies of high-inoculum infections, such as endocarditis. This retrospective study compares clinical outcomes of cefazolin versus oxacillin for complicated MSSA bacteremia at two tertiary care hospitals between January 2008 and June 2012. Fifty-nine patients treated with cefazolin and 34 patients treated with oxacillin were included. Osteoarticular (41%) and endovascular (20%) sources were the predominant sites of infection. The rates of clinical cure at the end of therapy were similar between cefazolin and oxacillin (95% versus 88%; P = 0.25), but overall failure at 90 days was higher in the oxacillin arm (47% versus 24%; P = 0.04). Failures were more likely to have received surgical interventions (63% versus 40%; P = 0.05) and to have an osteoarticular source (57% versus 33%; P = 0.04). Failures also had a longer duration of bacteremia (7 versus 3 days; P = 0.0002), which was the only predictor of failure. Antibiotic selection was not predictive of failure. Rates of adverse drug events were higher in the oxacillin arm (30% versus 3%; P = 0.0006), and oxacillin was more frequently discontinued due to adverse drug events (21% versus 3%; P = 0.01). Cefazolin appears similar to oxacillin for the treatment of complicated MSSA bacteremia but with significantly improved safety. The higher rates of failure with oxacillin may have been confounded by other patient factors and warrant further investigation.Pharmac

Aggradation and progradation controlled clinothems and deep-water sand delivery model in the Neogene Lake Pannon, Makó Trough, Pannonian Basin, SE Hungary

In the Late Miocene–Early Pliocene Lake Pannon, regression went on for about 6 Ma. Sediments arriving from the Alpine–Carpathian source area were partly accumulated on the flat-lying morphological shelf of the lake, whereas other portions of the sediment were passing through to the slope and deposited on the deep basin floor. The height of the slope exceeded 400–500 mbased on correlated well and seismic data. An extended 3D seismic volume covering theMakó Trough, one of the largest and deepest depressions within the Pannonian Basin, provided an opportunity to study sequences and shelf-margin trajectories generated as a result of continuous slope advancement. The lithology of these shelf, slope and basin centre deposits was inferred fromseven well logs and 220 mcore material. In the Makó Trough the southeastward migrating shelf-margin was formed by alternating aggradational and progradational clinothems. Aggradational clinothems, i.e. aggradation accompanied by subordinate progradation, are characterised by rising shelf-margin trajectories. The shelf built up from inner-shelf to shelf-edge deltaic lobes which compose a few dozen metre thick coarsening-up units. The majority of the sand, however, was transported by effective turbidity currents through leveed channels into the basin, and deposited as thick, extended slopedetached turbidite lobes up to a distance of 30 km from the shelf edge. In aggradational clinothems both the shelf and the basin floor accreted vertically. Development of progradational clinothems resulted in horizontal (flat) shelf-margin trajectories. Corresponding reflections toplap at the shelf edge and downlap within a distance of few kilometres from the toe of the slope. The shelf was bypassed, sediments accumulated on the slope and directly at the slope–toe region as small simple lobes. Short-distance transport was the result of clay-poor, non-effective turbidity currents. Consequently, the thickness of coeval basin-centre sediments remained negligible in progradational clinothems. Alternations of rising and horizontal shelf margin trajectories indicate that the climate- and subsidence-controlled lacustrine base-level rose continuously, though at varying rates. Descending trajectories were not observed. It means that base-level drops larger in amplitude than the seismic resolution (20–30 m), did not occur during the studied time interval, i.e. at 7–5 Ma ago, approximately corresponding to the Messinian age. As a result, major forced-regressive wedges or lowstand fans did not develop. This is in contrast with former stratigraphic models claiming that several 3rd-order sequences, including the intra-Messinian unconformity supposedly induced by hundred metres large lake-level drop, developed in Lake Pannon with significant volume of lowstand deposits as turbidites. Instead, aggradational and progradational clinothems are interpreted as fourth-order transgressive, early and late highstand systems tracts. These incomplete sequences represent less than 100 kyr time intervals. Due to climate control both on high rate of sediment supply and the water budget of Lake Pannon, conditions were more favourable for deposition of large volumes of well-developed turbidite systems during base-level rise than during stagnation or minor base-level fall. Therefore, sand delivery to the basin centre was at maximum during the early highstand aggradational stage and atminimum during the late highstand progradational stage. The timing and position of sand accumulation in the Makó Trough of Lake Pannon is different from those predicted by “traditional” sequence stratigraphic considerations

Continuous versus Intermittent Infusion of Oxacillin for Treatment of Infective Endocarditis Caused by Methicillin-Susceptible Staphylococcus aureus▿

Infective endocarditis (IE) is the fourth leading cause of life-threatening infection in the United States and imposes significant morbidity and mortality. The American Heart Association guidelines for the diagnosis and treatment of IE do not address continuous-infusion (CI) oxacillin. This retrospective study compares outcomes between CI oxacillin and intermittent-infusion (II) oxacillin in the treatment of IE caused by methicillin-susceptible Staphylococcus aureus (MSSA). A total of 709 medical records were reviewed for inpatients with definitive IE treated between 1 January 2000 and 31 December 2007. Continuous data were analyzed by Student's t test or the Wilcoxon rank sum test. The chi-square test or Fisher's exact test was used to compare nominal data. A multivariate logistic model was constructed. One hundred seven patients met eligibility criteria for inclusion into the study. Seventy-eight patients received CI oxacillin, whereas 28 received II oxacillin. CI and II groups were similar with respect to 30-day mortality (8% versus 10%, P = 0.7) and length of stay (20 versus 25 days, P = 0.4) but differed in 30-day microbiological cure (94% versus 79%, P = 0.03). Sixty-three patients received synergistic gentamicin, whereas 44 did not. The gentamicin and no-gentamicin groups were similar with respect to 30-day mortality (11% versus 4%, P = 0.2) and 30-day microbiological cure (90% versus 89%, P = 0.8); however, times to defervescence (4 versus 2 days, P = 0.02) were significantly different. CI oxacillin is an effective alternative to II oxacillin for the treatment of IE caused by MSSA and may improve microbiological cure. This convenient and pharmacodynamically optimized dosing regimen for oxacillin deserves consideration for patients with IE caused by MSSA

Stress phase angle depicts differences in coronary artery hemodynamics due to changes in flow and geometry after percutaneous coronary intervention

The effects of changes in flow velocity waveform and arterial geometry before and after percutaneous coronary intervention (PCI) in the right coronary artery (RCA) were investigated using computational fluid dynamics. An RCA from a patient with a stenosis was reconstructed based on multislice computerized tomography images. A nonstenosed model, simulating the same RCA after PCI, was also constructed. The blood flows in the RCA models were simulated using pulsatile flow waveforms acquired with an intravascular ultrasound-Doppler probe in the RCA of a patient undergoing PCI. It was found that differences in the waveforms before and after PCI did not affect the time-averaged wall shear stress and oscillatory shear index, but the phase angle between pressure and wall shear stress on the endothelium, stress phase angle (SPA), differed markedly. The median SPA was −63.9° (range, −204° to −10.0°) for the pre-PCI state, whereas it was 10.4° (range, −71.1° to 25.4°) in the post-PCI state, i.e., more asynchronous in the pre-PCI state. SPA has been reported to influence the secretion of vasoactive molecules (e.g., nitric oxide, PGI2, and endothelin-1), and asynchronous SPA (≈−180°) is proposed to be proatherogenic. Our results suggest that differences in the pulsatile flow waveform may have an important influence on atherogenesis, although associated with only minor changes in the time-averaged wall shear stress and oscillatory shear index. SPA may be a useful indicator in predicting sites prone to atherosclerosis

Hemodynamic Response to Intravenous Adenosine and Its Effect on Fractional Flow Reserve Assessment:Results of the Adenosine for the Functional Evaluation of Coronary Stenosis Severity (AFFECTS) Study

Background— We studied the hemodynamic response to intravenous adenosine on calculation of fractional flow reserve (FFR). Intravenous adenosine is widely used to achieve conditions of stable hyperemia for measurement of FFR. However, intravenous adenosine affects both systemic and coronary vascular beds differentially. Methods and Results— A total of 283 patients (310 coronary stenoses) underwent coronary angiography with FFR using intravenous adenosine 140 mcg/kg per minute via a central femoral vein. Offline analysis was performed to calculate aortic (Pa), distal intracoronary (Pd), and reservoir (Pr) pressure at baseline, peak, and stable hyperemia. Seven different hemodynamic patterns were observed according to Pa and Pd change at peak and stable hyperemia. The average time from baseline to stable hyperemia was 68.2±38.5 seconds, when both ΔPa and ΔPd were decreased (ΔPa, −10.2±10.5 mm Hg; ΔPd, −18.2±10.8 mm Hg; P &lt;0.001 for both). The fall in Pa closely correlated with the reduction in peripheral Pr (ΔPr, −12.9±15.7 mm Hg; P &lt;0.001; r =0.9; P &lt;0.001). ΔPa and ΔPd were closely related under conditions of peak ( r =0.75; P &lt;0.001) and stable hyperemia ( r =0.83; P &lt;0.001). On average, 56% (10.2 mm Hg) of the reduction in Pd was because of fall in Pa. FFR lesion classification changed in 9% using an FFR threshold of ≤0.80 and 5.2% with FFR threshold &lt;0.75 when comparing Pd/Pa at peak and stable hyperemia. Conclusions— Intravenous adenosine results in variable changes in systemic blood pressure, which can lead to alterations in FFR lesion classification. Attention is required to ensure FFR is measured under conditions of stable hyperemia, although the FFR value at this point may be numerically higher. </jats:sec

Baseline instantaneous wave-free ratio as a pressure-only estimation of underlying coronary flow reserve: results of the JUSTIFY-CFR Study (Joined Coronary Pressure and Flow Analysis to Determine Diagnostic Characteristics of Basal and Hyperemic Indices of Functional Lesion Severity-Coronary Flow Reserve)

Coronary flow reserve has extensive validation as a prognostic marker in coronary disease. Although pressure-only fractional flow reserve (FFR) improves outcomes compared with angiography when guiding percutaneous coronary intervention, it disagrees with coronary flow reserve classification 30% of the time. We evaluated whether baseline instantaneous wave-free ratio (iFR) could provide an improved pressure-only estimation of underlying coronary flow reserve. Invasive pressure and flow velocity were measured in 216 stenoses from 186 patients with coronary disease. The diagnostic relationship between pressure-only indices (iFR and FFR) and coronary flow velocity reserve (CFVR) was compared using correlation coefficient and the area under the receiver operating characteristic curve. iFR showed a stronger correlation with underlying CFVR (iFR-CFVR, ρ=0.68 versus FFR-CFVR, ρ=0.50; P 0.75; mean FFR flow, 42.3±22.8 cm/s versus mean iFR flow, 26.1±15.5 cm/s; P <0.001). When compared with FFR, iFR shows stronger correlation and better agreement with CFVR. These results provide physiological evidence that iFR could potentially be used as a functional index of disease severity, independently from its agreement with FF