Role of Thrombolestagrophy in Monitoring Perioperative Coagulation Status and Effect of Thromboprophylaxis in Bariatric Surgery

Background  

Thromboelastography is a technique that surveys the properties of viscoelastic blood clot. The purpose of this paper was to evaluate the hypercoagulability state and the effect of antithrombotic prophylaxis on thromboelastogram (TEG) results in bariatric surgery.     

Single-dose azithromycin microspheres vs clarithromycin extended release for the treatment of mild-to-moderate community-acquired pneumonia in adults

BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. The inability or failure of many subjects to adhere to standard antibiotic regimens, which may last up to 10 days, results in suboptimal antibiotic treatment. Treatment with a single-dose antibiotic regimen may improve compliance with prescribed therapy. A novel microsphere formulation of azithromycin provides a single-dose regimen while maintaining tolerability. STUDY OBJECTIVE: To compare the efficacy and safety of a single 2.0-g dose of azithromycin microspheres to that of an extended-release formulation of clarithromycin (1.0 g/d for 7 days) for the treatment of adults with mild-to-moderate CAP. DESIGN: A phase III, multinational, multicenter, randomized, double-blind, double-dummy study, comparing single-dose azithromycin microspheres to extended-release clarithromycin, both administered orally. METHODS: Subjects with mild-to-moderate CAP (Fine class I and II) were included. The primary end point was clinical response at the test-of-cure (TOC) visit (days 14 to 21) in the clinical per protocol (CPP) population. The bacteriologic response at the TOC visit was assessed in subjects with a baseline pathogen. RESULTS: A total of 501 subjects were randomized, and 499 were treated. Clinical cure rates at the TOC visit in the CPP population were 92.6% (187 of 202 subjects) for azithromycin microspheres and 94.7% (198 of 209 subjects) for extended-release clarithromycin. Overall pathogen eradication rates were 91.8% (123 of 134 subjects) for azithromycin microspheres and 90.5% (153 of 169 subjects) for extended-release clarithromycin. Both agents were well tolerated. The incidence of treatment-related adverse events was 26.3% with azithromycin microspheres and 24.6% with extended-release clarithromycin. Most adverse events were mild to moderate in severity. CONCLUSION: A single 2.0-g dose of azithromycin microspheres was as effective and well tolerated as a 7-day course of extended-release clarithromycin in the treatment of adults with mild-to-moderate CAP.     

Liver injury with novel oral anticoagulants: assessing post-marketing reports in the US Food and Drug Administration adverse event reporting system

Aim

We assessed the hepatic safety of novel oral anticoagulants (NOACs) analyzing the publicly available US-FDA adverse event reporting system (FAERS).

Methods

We extracted reports of drug-induced liver injury (DILI) associated with NOACs, including acute liver failure (ALF) events. Based on US marketing authorizations, we performed disproportionality analyses, calculating reporting odds ratios (RORs) with 95% confidence interval (CI), also to test for event- and drug-related competition bias, and case-by-case evaluation for concomitant medications.

Results

DILI reports represented 3.7% (n = 146) and 1.7% (n = 222) of all reports for rivaroxaban and dabigatran, respectively. No statistically significant association was found for dabigatran, in primary and secondary analyses. Disproportionality signals emerged for rivaroxaban in primary analysis (ALF: n = 25, ROR = 2.08, 95% CI 1.34, 3.08). In a large proportion of DILI reports concomitant hepatotoxic and/or interacting drugs were recorded: 42% and 37% (rivaroxaban and dabigatran, respectively), especially statins, paracetamol and amiodarone. Among ALF reports, fatal outcome occurred in 49% of cases (44% and 51%, rivaroxaban and dabigatran, respectively), whereas rapid onset of the event (<1 week) was detected in 46% of patients (47% and 44%, respectively).

Conclusions

The disproportionality signal for rivaroxaban calls for further comparative population-based studies to characterize and quantify the actual DILI risk of NOACs, taking into account drug- and patient-related risk factors. As DILI is unpredictable, our findings strengthen the role of (a) timely pharmacovigilance to detect post-marketing signals of DILI through FAERS and other data sources, (b) clinicians to assess early, on a case-by-case basis, the potential responsibility of NOACs when they diagnose a liver injury.     

Echocardiography predicts embolic events in infective endocarditis

OBJECTIVES: The aim of our study was to assess the value of transesophageal echocardiography (TEE) in predicting embolic events (EEs) in a large group of patients with definite endocarditis according to the Duke criteria, including silent embolism. BACKGROUND: The value of echocardiography in predicting embolism in patients with endocarditis remains controversial. Some studies reported an increased risk of embolism in patients with large and mobile vegetations, whereas other studies failed to demonstrate such a relationship. METHODS: Multiplane transesophageal echocardiograms of 178 consecutive patients with definite infective endocarditis (IE) were analyzed. The incidence of embolism was compared with the echocardiographic characteristics (localization, size and mobility) of the vegetations. To detect silent embolism, cerebral and thoraco-abdominal scans were performed in 95% of patients. RESULTS: Among 178 patients, 66 (37%) had one or more EEs. There was no difference between patients with and without embolism in terms of age, gender and left valve involved. On univariate analysis, Staphylococcus infection, right-side valve endocarditis and vegetation length and mobility were significantly related to EEs. A significant higher incidence of embolism was present in patients with vegetation length >10 mm (60%, p < 0.001) and in patients with mobile vegetations (62%, p < 0.001). Embolism was particularly frequent among 30 patients with both severely mobile and large vegetations (> 15 mm) (83%, p < 0.001). On multivariate analysis, the only predictors of embolism were vegetation length (p = 0.03) and mobility (p = 0.01). CONCLUSIONS: Our study shows that the presence of vegetations on TEE is predictive of embolism and that the morphologic characteristics of vegetations are helpful in predicting EEs in both mitral and aortic valve IE. It also suggests that early operation may be recommended in patients with vegetations > 15 mm and high mobility, irrespective of the degree of valve destruction, heart failure and response to antibiotic therapy.     

Proteases and chronic leg ulcers

AIM: The aim of this study was to compare the effect of cadexomer on reducing wound surface area of leg ulcers compared to that obtained in a group patients whose ulcers were treated by compression therapy. METHODS: For each ulcer group, wound surface area was calculated at day 0 and after 28 days of treatment: this allowed to calculate the average wound surface area reduction, the percent reduction in wound size, as well as the weekly wound size reduction index. RESULTS: In the cadexomer-treated ulcers the total wound area reduction was 9.67 cm(2)/week, with a weekly wound size reduction index per patient of 0.96 cm(2); in the controls (compression therapy-treated patients) the total wound area reduction was 6.11 cm(2)/week, with a weekly reduction index per patient of 0.61 cm(2). At the end of treatment, in the group of patients whose ulcers were treated with cadexomer ointment the average wound size reduction was 43%, whereas in the control-treated patient group the average wound size reduction was 28%. CONCLUSION: These data suggest that cadexomer can play an important role in the healing of chronic leg ulcers.     

Anxiety,depression, and quality of life in Parkinson’s disease: the implications of multidisciplinary treatment

Anxiety and depression in Parkinson’s disease (PD) reduce well-being of the patients. Emotional alterations influence motor skills and cognitive performance; moreover, they contribute significantly and independently to worsen rehabilitative treatment response. We investigated anxiety, depression, and quality of life in PD patients subjected to multidisciplinary rehabilitative training. The self-controlled study included 100 PD patients (49 males and 51 females with the mean age of 64.66 years) admitted to 60 days hospitalization rehabilitative program, between January 2017 and December 2018. Motor, cognitive, linguistic abilities, and functional independence were evaluated at admission (T0 baseline visit) and 60 days after (T1) the multidisciplinary rehabilitation including motor exercises, speech therapies, and cognitive intervention. The multidisciplinary rehabilitation improved functional status in PD patients and exerted its positive effects on mood, motor abilities, autonomy in the activities of daily life, perception of quality of life, cognitive performance and speech skills. Non-motor symptoms may worsen severe disability and reduce quality of life. They are often poorly recognized and inadequately treated. Nonetheless, multidisciplinary rehabilitative training represents an optimal strategy to improve disease management. The study was approved by Istituito di Ricovero e Cura a Carattere Scientifico (IRCCS) Centro Neurolesi “Bonino-Pulejo” Ethical Committee (approval No. 6/2016) in June 2016.     

Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder

Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala–calcarine (P=0.01) and amygdala–thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala–ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma.     

In patients with COPD, treatment with a combination of formoterol and ipratropium is more effective than a combination of salbutamol and ipratropium : a 3-week, randomized, double-blind, within-patient, multicenter study

STUDY OBJECTIVES: To compare the efficacy of adding formoterol or salbutamol to regular ipratropium bromide treatment in COPD patients whose conditions were suboptimally controlled with ipratropium bromide alone. DESIGN: A randomized, double-blind, double-dummy, two-period, crossover clinical trial. SETTING: Twenty-four clinics and university medical centers in nine countries. PATIENTS: One hundred seventy-two patients with baseline FEV(1) < or = 65% predicted, with FEV(1) reversibility to salbutamol not exceeding the normal variability of the measurement, and symptomatic despite regular treatment with ipratropium bromide. INTERVENTIONS: Each patient received two treatments in random order: either inhaled formoterol dry powder, 12 microg bid, in addition to ipratropium bromide, 40 microg qid for 3 weeks, followed by salbutamol, 200 microg qid, in addition to ipratropium, 40 microg qid for 3 weeks, or vice versa. MEASUREMENTS AND RESULTS: Efficacy end points included morning premedication peak expiratory flow (PEF) during the last week of treatment (primary end point), the area under the curve (AUC) for FEV(1) measured for 6 h after morning dose on the last day of treatment, and symptom scores (from daily diary recordings). Morning PEF and the AUC for FEV(1) were significantly better for formoterol/ipratropium than for salbutamol/ipratropium (p = 0.0003 and p < 0.0001, respectively). The formoterol/ipratropium combination also induced a greater improvement in mean total symptom scores (p = 0.0042). The safety profile of the two treatments was comparable. CONCLUSIONS: In COPD patients requiring combination bronchodilator treatment, the addition of formoterol to regular ipratropium treatment is more effective than the addition of salbutamol.