Safety and effectiveness of bariatric surgery: Roux-en-y gastric bypass is superior to gastric banding in the management of morbidly obese patients: a reply to the response by Bhoyrul et al

ABSTRACT: BACKGROUND: We have read the letter by Bhoyrul et al. in response to our recently published article "Safety and effectiveness of bariatric surgery: Roux-en-Y gastric bypass is superior to gastric banding in the management of morbidly obese patients". We strongly disagree with the content of the letter. RESULTS AND DISCUSSION: Bhoyrul et al. base their letter mostly on low level evidence such as single-institutional case series (level IV evidence) and expert opinion (level V evidence). Surprisingly, they do not comment on the randomized controlled trial, which clearly favours gastric bypass over gastric banding. CONCLUSION: The letter by Bhoyrul et al. is based on low level evidence and is itself biased, unsubstantiated, and not supported by the current literature.

Traffic Routes and Signals for the Tonoplast

Tonoplast, the membrane delimiting plant vacuoles, regulates ion, water and nutrient movement between the cytosol and the vacuolar lumen through the activity of its membrane proteins. Correct traffic of proteins from the endoplasmic reticulum (ER) to the tonoplast requires (i) approval by the ER quality control, (ii) motifs for exit from the ER and (iii) motifs that promote sorting to the tonoplast. Recent evidence suggests that this traffic follows different pathways that are protein-specific and could also reflect vacuole specialization for lytic or storage function. The routes can be distinguished based on their sensitivity to drugs such as brefeldin A and C834 as well as using mutant plants that are defective in adaptor proteins of vesicle coats, or dominant-negative mutants of Rab GTPases.

Improved safety and reduction in stent thrombosis associated with biodegradable polymer-based biolimus-eluting stents versus durable polymer-based sirolimus-eluting stents in patients with coronary artery disease: final 5-year report of the LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) randomized, noninferiority trial

OBJECTIVES This study sought to report the final 5 years follow-up of the landmark LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) trial. BACKGROUND The LEADERS trial is the first randomized study to evaluate biodegradable polymer-based drug-eluting stents (DES) against durable polymer DES. METHODS The LEADERS trial was a 10-center, assessor-blind, noninferiority, "all-comers" trial (N = 1,707). All patients were centrally randomized to treatment with either biodegradable polymer biolimus-eluting stents (BES) (n = 857) or durable polymer sirolimus-eluting stents (SES) (n = 850). The primary endpoint was a composite of cardiac death, myocardial infarction (MI), or clinically indicated target vessel revascularization within 9 months. Secondary endpoints included extending the primary endpoint to 5 years and stent thrombosis (ST) (Academic Research Consortium definition). Analysis was by intention to treat. RESULTS At 5 years, the BES was noninferior to SES for the primary endpoint (186 [22.3%] vs. 216 [26.1%], rate ratio [RR]: 0.83 [95% confidence interval (CI): 0.68 to 1.02], p for noninferiority <0.0001, p for superiority = 0.069). The BES was associated with a significant reduction in the more comprehensive patient-orientated composite endpoint of all-cause death, any MI, and all-cause revascularization (297 [35.1%] vs. 339 [40.4%], RR: 0.84 [95% CI: 0.71 to 0.98], p for superiority = 0.023). A significant reduction in very late definite ST from 1 to 5 years was evident with the BES (n = 5 [0.7%] vs. n = 19 [2.5%], RR: 0.26 [95% CI: 0.10 to 0.68], p = 0.003), corresponding to a significant reduction in ST-associated clinical events (primary endpoint) over the same time period (n = 3 of 749 vs. n = 14 of 738, RR: 0.20 [95% CI: 0.06 to 0.71], p = 0.005). CONCLUSIONS The safety benefit of the biodegradable polymer BES, compared with the durable polymer SES, was related to a significant reduction in very late ST (>1 year) and associated composite clinical outcomes. (Limus Eluted From A Durable Versus ERodable Stent Coating [LEADERS] trial; NCT00389220).

Safety and efficacy of drug-eluting stents in women: a patient-level pooled analysis of randomised trials

BACKGROUND The safety and efficacy of drug-eluting stents (DES) in the treatment of coronary artery disease have been assessed in several randomised trials. However, none of these trials were powered to assess the safety and efficacy of DES in women because only a small proportion of recruited participants were women. We therefore investigated the safety and efficacy of DES in female patients during long-term follow-up. METHODS We pooled patient-level data for female participants from 26 randomised trials of DES and analysed outcomes according to stent type (bare-metal stents, early-generation DES, and newer-generation DES). The primary safety endpoint was a composite of death or myocardial infarction. The secondary safety endpoint was definite or probable stent thrombosis. The primary efficacy endpoint was target-lesion revascularisation. Analysis was by intention to treat. FINDINGS Of 43,904 patients recruited in 26 trials of DES, 11,557 (26·3%) were women (mean age 67·1 years [SD 10·6]). 1108 (9·6%) women received bare-metal stents, 4171 (36·1%) early-generation DES, and 6278 (54·3%) newer-generation DES. At 3 years, estimated cumulative incidence of the composite of death or myocardial infarction occurred in 132 (12·8%) women in the bare-metal stent group, 421 (10·9%) in the early-generation DES group, and 496 (9·2%) in the newer-generation DES group (p=0·001). Definite or probable stent thrombosis occurred in 13 (1·3%), 79 (2·1%), and 66 (1·1%) women in the bare-metal stent, early-generation DES, and newer-generation DES groups, respectively (p=0·01). The use of DES was associated with a significant reduction in the 3 year rates of target-lesion revascularisation (197 [18·6%] women in the bare-metal stent group, 294 [7·8%] in the early-generation DES group, and 330 [6·3%] in the newer-generation DES group, p<0·0001). Results did not change after adjustment for baseline characteristics in the multivariable analysis. INTERPRETATION The use of DES in women is more effective and safe than is use of bare-metal stents during long-term follow-up. Newer-generation DES are associated with an improved safety profile compared with early-generation DES, and should therefore be thought of as the standard of care for percutaneous coronary revascularisation in women. FUNDING Women in Innovation Initiative of the Society of Cardiovascular Angiography and Interventions.

A reliable, traffic-adaptive and energy-efficient link layer for wireless sensor networks

The paper presents a link layer stack for wireless sensor networks, which consists of the Burst-aware Energy-efficient Adaptive Medium access control (BEAM) and the Hop-to-Hop Reliability (H2HR) protocol. BEAM can operate with short beacons to announce data transmissions or include data within the beacons. Duty cycles can be adapted by a traffic prediction mechanism indicating pending packets destined for a node and by estimating its wake-up times. H2HR takes advantage of information provided by BEAM such as neighbour information and transmission information to perform per-hop congestion control. We justify the design decisions by measurements in a real-world wireless sensor network testbed and compare the performance with other link layer protocols.

Traffic-Adaptive and Link-Quality-Aware Communication in Wireless Sensor Networks

This paper is a summary of the main contribu- tions of the PhD thesis published in [1]. The main research contributions of the thesis are driven by the research question how to design simple, yet efficient and robust run-time adaptive resource allocation schemes within the commu- nication stack of Wireless Sensor Network (WSN) nodes. The thesis addresses several problem domains with con- tributions on different layers of the WSN communication stack. The main contributions can be summarized as follows: First, a a novel run-time adaptive MAC protocol is intro- duced, which stepwise allocates the power-hungry radio interface in an on-demand manner when the encountered traffic load requires it. Second, the thesis outlines a metho- dology for robust, reliable and accurate software-based energy-estimation, which is calculated at network run- time on the sensor node itself. Third, the thesis evaluates several Forward Error Correction (FEC) strategies to adap- tively allocate the correctional power of Error Correcting Codes (ECCs) to cope with timely and spatially variable bit error rates. Fourth, in the context of TCP-based communi- cations in WSNs, the thesis evaluates distributed caching and local retransmission strategies to overcome the perfor- mance degrading effects of packet corruption and trans- mission failures when transmitting data over multiple hops. The performance of all developed protocols are eval- uated on a self-developed real-world WSN testbed and achieve superior performance over selected existing ap- proaches, especially where traffic load and channel condi- tions are suspect to rapid variations over time.

Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases

A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

Safety and Feasibility of a Diagnostic Algorithm Combining Clinical Probability, d-Dimer Testing, and Ultrasonography for Suspected Upper Extremity Deep Venous Thrombosis: A Prospective Management Study.

BACKGROUND Although well-established for suspected lower limb deep venous thrombosis, an algorithm combining a clinical decision score, d-dimer testing, and ultrasonography has not been evaluated for suspected upper extremity deep venous thrombosis (UEDVT). OBJECTIVE To assess the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT. DESIGN Diagnostic management study. (ClinicalTrials.gov: NCT01324037) SETTING: 16 hospitals in Europe and the United States. PATIENTS 406 inpatients and outpatients with suspected UEDVT. MEASUREMENTS The algorithm consisted of the sequential application of a clinical decision score, d-dimer testing, and ultrasonography. Patients were first categorized as likely or unlikely to have UEDVT; in those with an unlikely score and normal d-dimer levels, UEDVT was excluded. All other patients had (repeated) compression ultrasonography. The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a normal diagnostic work-up. RESULTS The algorithm was feasible and completed in 390 of the 406 patients (96%). In 87 patients (21%), an unlikely score combined with normal d-dimer levels excluded UEDVT. Superficial venous thrombosis and UEDVT were diagnosed in 54 (13%) and 103 (25%) patients, respectively. All 249 patients with a normal diagnostic work-up, including those with protocol violations (n = 16), were followed for 3 months. One patient developed UEDVT during follow-up, for an overall failure rate of 0.4% (95% CI, 0.0% to 2.2%). LIMITATIONS This study was not powered to show the safety of the substrategies. d-Dimer testing was done locally. CONCLUSION The combination of a clinical decision score, d-dimer testing, and ultrasonography can safely and effectively exclude UEDVT. If confirmed by other studies, this algorithm has potential as a standard approach to suspected UEDVT. PRIMARY FUNDING SOURCE None.

Automated low flow pump system for the treatment of refractory ascites: A multi-center safety and efficacy study

BACKGROUND & AIMS: Refractory ascites (RA) affects 10% of patients with advanced cirrhosis and ascites. Usual therapy includes large volume paracentesis, and in selected patients, a transjugular portosystemic shunt (TIPS). These therapies may be associated with increased morbidity: paracentesis may induce circulatory dysfunction and impair quality of life and TIPS may induce encephalopathy and is associated with increased mortality in patients with severe liver dysfunction. We present the results of a multicenter, non-randomized trial to assess the safety and efficacy of a new automated pump system for treatment of RA. METHODS: Forty patients at 9 centers (February 2010-June 2011) received an implanted pump for the automated removal of ascites from the peritoneal cavity into the bladder, from where it was eliminated through normal urination. Patients were followed-up for 6months. The primary study outcome was safety. Secondary outcomes included recurrence of tense ascites and pump performance. RESULTS: Surgical complications occurred early in the study and became less frequent. The pump system removed 90% of the ascites and significantly reduced the median number of large volume paracentesis per month [3.4 (range 1-6) vs. 0.2 (range 0-4); p <0.01]. Cirrhosis-related adverse events decreased along follow-up. CONCLUSIONS: The automated pump seems an efficacious tool to move out ascites from the peritoneal cavity to the bladder. Its safety is still moderate, but a broad use in different countries will improve the surgical technique as well as the medical surveillance. A prospective randomized clinical trial vs. large volume paracentesis is underway to confirm these preliminary results.

Safety and efficacy of thrombolysis with intravenous alteplase in older stroke patients.

Stroke is a common cause of death and persisting disability worldwide, and thrombolysis with intravenous alteplase is the only approved treatment for acute ischaemic stroke. Older age is the most important non-modifiable risk factor for stroke, and demographic changes are also resulting in an increasingly ageing population. However, clinical trial evidence for the use of intravenous alteplase is limited for the older age group where stroke incidence is highest. In this article, the current evidence regarding the safety and efficacy of intravenous thrombolytic therapy in stroke patients aged ≥80 years is critically analysed and the gap in current knowledge highlighted. In summary, intravenous thrombolysis in stroke patients aged ≥80 years seems to be associated with less favourable clinical outcomes and higher mortality than in younger patients, which is consistent with the natural course in untreated patients. The risk of symptomatic intracranial haemorrhage does not appear to be significantly higher in the elderly group, suggesting that intracranial bleeding complications are unlikely to outweigh the potential benefit in this age group. Overall, withholding thrombolytic treatment in ischaemic stroke on the basis of advanced age alone is no longer justifiable.

Age dependency of safety and outcome of endovascular therapy for acute stroke

Elderly patients generally experience less favorable outcomes and higher mortality after acute stroke than younger patients. The aim of this study was to analyze the influence of age on outcome and safety after endovascular therapy in a large cohort of patients aged between 20 and 90 years. We prospectively acquired data of 1,000 stroke patients treated with endovascular therapy at a single center. Logistic regression analysis was performed to determine predictors of outcome and linear regression analysis to evaluate the association of age and outcome after 3 months. Younger age was an independent predictor of favorable outcome (OR 0.954, p < 0.001) and survival (OR 0.947, p < 0.001) in multivariate regression analysis. There was a linear relationship between age and outcome. Ever increase in 26 years of age was associated with an increase in the modified Rankin Scale of 1 point (p < 0.001). However, increasing age was not a risk factor for symptomatic (p = 0.086) or asymptomatic (p = 0.674) intracerebral hemorrhage and did not influence recanalization success (p = 0.674). Advancing age was associated with a decline of favorable outcomes and survival after endovascular therapy. This decline was linear from age 20 to 90 years, but was not related to lower recanalization rates or higher bleeding risk in the elderly. The efficacy of endovascular stroke therapy seems to be preserved also in the elderly and other factors than efficacy of endovascular therapy such as decreased plasticity are likely to explain the worse outcome with advancing age.

Feeling present in arousing virtual reality worlds: prefrontal brain regions differentially orchestrate presence experience in adults and children

Virtual reality (VR) is a powerful tool for simulating aspects of the real world. The success of VR is thought to depend on its ability to evoke a sense of "being there", that is, the feeling of "Presence". In view of the rapid progress in the development of increasingly more sophisticated virtual environments (VE), the importance of understanding the neural underpinnings of presence is growing. To date however, the neural correlates of this phenomenon have received very scant attention. An fMRI-based study with 52 adults and 25 children was therefore conducted using a highly immersive VE. The experience of presence in adult subjects was found to be modulated by two major strategies involving two homologous prefrontal brain structures. Whereas the right DLPFC controlled the sense of presence by down-regulating the activation in the egocentric dorsal visual processing stream, the left DLPFC up-regulated widespread areas of the medial prefrontal cortex known to be involved in self-reflective and stimulus-independent thoughts. In contrast, there was no evidence of these two strategies in children. In fact, anatomical analyses showed that these two prefrontal areas have not yet reached full maturity in children. Taken together, this study presents the first findings that show activation of a highly specific neural network orchestrating the experience of presence in adult subjects, and that the absence of activity in this neural network might contribute to the generally increased susceptibility of children for the experience of presence in VEs.

Virtual reality and the role of the prefrontal cortex in adults and children

In this review, the neural underpinnings of the experience of presence are outlined. Firstly, it is shown that presence is associated with activation of a distributed network, which includes the dorsal and ventral visual stream, the parietal cortex, the premotor cortex, mesial temporal areas, the brainstem and the thalamus. Secondly, the dorsolateral prefrontal cortex (DLPFC) is identified as a key node of the network as it modulates the activity of the network and the associated experience of presence. Thirdly, children lack the strong modulatory influence of the DLPFC on the network due to their unmatured frontal cortex. Fourthly, it is shown that presence-related measures are influenced by manipulating the activation in the DLPFC using transcranial direct current stimulation (tDCS) while participants are exposed to the virtual roller coaster ride. Finally, the findings are discussed in the context of current models explaining the experience of presence, the rubber hand illusion, and out-of-body experiences.

The Impact of Renal Impairment on Long-Term Safety and Effectiveness of Drug-Eluting Stents

BACKGROUND Renal impairment (RI) is associated with impaired prognosis in patients with coronary artery disease. Clinical and angiographic outcomes of patients undergoing percutaneous coronary intervention (PCI) with the use of drug-eluting stents (DES) in this patient population are not well established. METHODS We pooled individual data for 5,011 patients from 3 trials with the exclusive and unrestricted use of DES (SIRTAX - N = 1,012, LEADERS - N = 1,707, RESOLUTE AC - N = 2,292). Angiographic follow-up was available for 1,544 lesions. Outcomes through 2 years were stratified according to glomerular filtration rate (normal renal function: GFR≥90 ml/min; mild RI: 90and MI (OR 2.02, 95%CI 1.19-3.43) compared with patients with normal renal function at 2 years follow-up. There was no difference in cardiac death or MI between patients with mild RI compared to those with normal renal function (OR 1.10, 95%CI 0.75-1.61). The risk of target-lesion revascularization was similar for patients with moderate/severe RI (OR 1.17, 95%CI 0.70-1.95) and mild RI (OR 1.16, 95%CI 0.81-1.64) compared with patients with normal renal function. In-stent late loss and in-segment restenosis were not different for patients with moderate/severe RI, mild RI, and normal renal function. CONCLUSIONS Renal function does not affect clinical and angiographic effectiveness of DES. However, prognosis remains impaired among patients with moderate/severe RI.