Improved costs and outcomes with conscious sedation vs general anesthesia in TAVR patients: Time to wake up?

BackgroundTranscatheter aortic valve replacement (TAVR) has become a commonplace procedure for the treatment of aortic stenosis in higher risk surgical patients. With the high cost and steadily increasing number of patients receiving TAVR, emphasis has been placed on optimizing outcomes as well as resource utilization. Recently, studies have demonstrated the feasibility of conscious sedation in lieu of general anesthesia for TAVR. This study aimed to investigate the clinical as well as cost outcomes associated with conscious sedation in comparison to general anesthesia in TAVR.MethodsRecords for all adult patients undergoing TAVR at our institution between August 2012 and June 2016 were included using our institutional Society of Thoracic Surgeons (STS) and American College of Cardiology (ACC) registries. Cost data was gathered using the BIOME database. Patients were stratified into two groups according to whether they received general anesthesia (GA) or conscious sedation (CS) during the procedure. No-replacement propensity score matching was done using the validated STS predicted risk of mortality (PROM) as a propensity score. Primary outcome measure with survival to discharge and several secondary outcome measures were also included in analysis. According to our institution's data reporting guidelines, all cost data is presented as a percentage of the general anesthesia control group cost.ResultsOf the 231 patients initially identified, 225 (157 GA, 68 CS) were included for analysis. After no-replacement propensity score matching, 196 patients (147 GA, 49 CS) remained. Overall mortality was 1.5% in the matched population with a trend towards lower mortality in the CS group. Conscious sedation was associated with significantly fewer ICU hours (30 vs 96 hours, p = <0.001) and total hospital days (4.9 vs 10.4, p<0.001). Additionally, there was a 28% decrease in direct cost (p<0.001) as well as significant decreases in all individual all cost categories associated with the use of conscious sedation. There was no difference in composite major adverse events between groups. These trends remained on all subsequent subgroup analyses.ConclusionConscious sedation is emerging as a safe and viable option for anesthesia in patients undergoing transcatheter aortic valve replacement. The use of conscious sedation was not only associated with similar rates of adverse events, but also shortened ICU and overall hospital stays. Finally, there were significant decreases in all cost categories when compared to a propensity matched cohort receiving general anesthesia

Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart

This is the final version. It was first published by Wiley in The Journal of Physiology at http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.275263/abstract.Hypoxic exposure is associated with impaired cardiac energetics in humans and altered mitochondrial function, with suppressed complex I-supported respiration, in rat heart. This response might limit reactive oxygen species (ROS) generation, but at the cost of impaired electron transport chain (ETC) activity. Dietary nitrate supplementation improves mitochondrial efficiency and can promote tissue oxygenation by enhancing blood flow. We therefore hypothesised that ETC dysfunction, impaired energetics and oxidative damage in the hearts of rats exposed to chronic hypoxia could be alleviated by sustained administration of a moderate dose of dietary nitrate. Male Wistar rats (n=40) were given water supplemented with 0.7 mmol/L NaCl (as control) or 0.7 mmol/L NaNO3, elevating plasma nitrate levels by 80%, and were exposed to 13% O2 (hypoxia) or normoxia (n=10 per group) for 14 days. Respiration rates, ETC protein levels, mitochondrial density, ATP content and protein carbonylation were measured in cardiac muscle. Complex I respiration rates and protein levels were 33% lower in hypoxic/NaCl rats compared with normoxic/NaCl controls. Protein carbonylation was 65% higher in hearts of hypoxic rats compared with controls, indicating increased oxidative stress, whilst ATP levels were 62% lower. Respiration rates, complex I protein and activity, protein carbonylation and ATP levels were all fully protected in the hearts of nitrate-supplemented hypoxic rats. Both in normoxia and hypoxia, dietary nitrate suppressed cardiac arginase expression and activity and markedly elevated cardiac L-arginine concentrations, unmasking a novel mechanism of action by which nitrate enhances tissue NO bioavailability. Dietary nitrate therefore alleviates metabolic abnormalities in the hypoxic heart, improving myocardial energetics

The X-ray Spectra of Black Hole X-ray Novae in Quiescence as Measured by Chandra

We present Chandra observations of black hole X-ray novae V404 Cyg, A0620-00, GRO J1655-40 and XTE J1550-564 in quiescence. Their quiescent spectra can be well fitted by a power-law model with slope $\alpha \sim 2$. While a coronal (Raymond-Smith) model is also a statistically acceptable representation of the spectra, the best fit temperatures of these models is $\sim 5$ times higher than that seen in active stellar coronae. These four spectra of quiescent X-ray novae are all consistent with that expected for accretion via an advection-dominated accretion flow (ADAF) and inconsistent with that expected from a stellar corona. This evidence for continued accretion in quiescence further strengthens the case for the existence of event horizons in black holes. Both A0620-00 and GRO J1655-40 were fainter than in previous observations, while V404 Cyg was more luminous and varied by a factor of 2 in a few ksec. A reanalysis of the X-ray data for XTE J1550-564 shows that (like V404 Cyg and A0620-00) its luminosity exceeds the maximum prediction of the coronal model by a large factor. The 0.3-7 keV luminosity of the four sources studied ranges from $\sim 10^{30}-10^{33}$ erg/s.Comment: 9 pages, 6 figures, accepted for publication in Ap

Extended scope of nursing practice: a multicentre randomised controlled trial of appropriately trained nurses and pre-registration house officers in pre-operative assessment in elective general surgery

Aim/ Principal Research Question:1) To determine whether pre-operative assessment carried out by an appropriately trained nurse (ATN) is equivalent in quality to that carried out by a pre-registration house officer (PRHO).2) To assess whether pre-assessments carried out by ATNs and PRHOs are equivalent in terms of cost.3) To determine whether assessments carried out by ATNs are acceptable to patients.4) To investigate the quality of communication between senior medical staff and ATNs.Factors of Interest:The extended role of appropriately trained nurses and pre-registration house officers in pre-operative assessment in elective general surgery.Methods:The study design was principally a prospective randomised equivalence trial but was accompanied by additional qualitative assessment of patient and staff perceptions, and an economic evaluation.The intervention consisted of a pre-operative assessment carried out by either an ATN or a PRHO. Of the patients who completed the study with a full evaluation, 926 patients were randomised to the PRHO arm of the trial and 948 to the ATN arm. Three ATNs took part in the study, one from each centre, together with a total of 87 PRHOs.Immediately following the initial assessment of a patient by a PRHO or an ATN, one of a number of clinical research fellows, all specialist registrars in anaesthetics, repeated the assessment and recorded it on a study form, together with a list of investigations required. The clinical research fellow then evaluated the competency of the initial assessor by comparing the quality of their assessment with their own. Any deficiencies in ordering of investigations and referral to other specialities were met in order to maximise patient care.Sample groups:All patients attending at one site for assessment prior to general anaesthetic for elective general, vascular, urological or breast surgery were potentially included in the study. Of 1907 patients who were randomised, 1874 completed the study with a full evaluation.The study was carried out at four NHS hospitals, three of which were teaching hospitals, in three NHS Trusts in Southampton, Sheffield and Doncaster.Outcome measures:Three areas of ATN and PRHO performance were judged separately, history taking, examination and ordering of tests, and each was graded into one of four categories, the most important of which was under-assessment, which would possibly have affected peri-operative management. In the case of ordering of tests, it was possible to have both over- and under-assessed a patient on different tests.Findings:The pre-operative assessments carried out by the ATNs were essentially equivalent to those performed by the PRHOs in terms of under-assessment that might possibly have affected peri-operative management, although there was variation between the ATNs in terms of the quality of history taking. This may be related to the low number of patients seen at one study site.PRHOs ordered significantly more unnecessary tests than the ATNs. The substitution of ATNs for PRHOs was calculated to be cost neutral.The results of the qualitative assessment showed that the use of ATNs for pre-operative assessment was acceptable to patients; however, there was no evidence that communication between senior medical staff and those carrying out pre-operative assessments was improved by their introduction.Conclusions:This study demonstrated no reason to inhibit the development of fully nurse-led pre-operative assessment, provided that the nurses are appropriately trained and maintain sufficient workload to retain skills.Implications for Further Research:Further research is needed in the following areas:1) the extent and type of training needed for nurses undertaking the pre-operative assessment role2) the use, costs and benefits of routine pre-operative testing.<br/

Origin and Dynamical Evolution of Neptune Trojans - I: Formation and Planetary Migration

We present the results of detailed dynamical simulations of the effect of the migration of the four giant planets on both the transport of pre-formed Neptune Trojans, and the capture of new Trojans from a trans-Neptunian disk. We find that scenarios involving the slow migration of Neptune over a large distance (50Myr to migrate from 18.1AU to its current location) provide the best match to the properties of the known Trojans. Scenarios with faster migration (5Myr), and those in which Neptune migrates from 23.1AU to its current location, fail to adequately reproduce the current day Trojan population. Scenarios which avoid disruptive perturbation events between Uranus and Neptune fail to yield any significant excitation of pre-formed Trojans (transported with efficiencies between 30 and 98% whilst maintaining the dynamically cold nature of these objects). Conversely, scenarios with periods of strong Uranus-Neptune perturbation lead to the almost complete loss of such pre-formed objects. In these cases, a small fraction (~0.15%) of these escaped objects are later recaptured as Trojans prior to the end of migration, with a wide range of eccentricities (<0.35) and inclinations (<40 deg). In all scenarios (including those with such disruptive interaction between Uranus and Neptune) the capture of objects from the trans-Neptunian disk (through which Neptune migrates) is achieved with efficiencies between ~0.1 and ~1%. The captured Trojans display a wide range of inclinations (<40 deg for slow migration, and <20 deg for rapid migration) and eccentricities (<0.35), and we conclude that, given the vast amount of material which undoubtedly formed beyond the orbit of Neptune, such captured objects may be sufficient to explain the entire Neptune Trojan population. (Shortened version)Comment: 25 pages, 6 figure

Formation and Dynamical Evolution of the Neptune Trojans - the Influence of the Initial Solar System Architecture

In this work, we investigate the dynamical stability of pre-formed Neptune Trojans under the gravitational influence of the four giant planets in compact planetary architectures, over 10 Myr. In our modelling, the initial orbital locations of Uranus and Neptune (aN) were varied to produce systems in which those planets moved on non-resonant orbits, or in which they lay in their mutual 1:2, 2:3 and 3:4 mean-motion resonances (MMRs). In total, 420 simulations were carried out, examining 42 different architectures, with a total of 840000 particles across all runs. In the non-resonant cases, the Trojans suffered only moderate levels of dynamical erosion, with the most compact systems (those with aN less than or equal 18 AU) losing around 50% of their Trojans by the end of the integrations. In the 2:3 and 3:4 MMR scenarios, however, dynamical erosion was much higher with depletion rates typically greater than 66% and total depletion in the most compact systems. The 1:2 resonant scenarios featured disruption on levels intermediate between the non-resonant cases and other resonant scenarios, with depletion rates of the order of tens of percent. Overall, the great majority of plausible pre-migration planetary architectures resulted in severe levels of depletion of the Neptunian Trojan clouds. In particular, if Uranus and Neptune formed near their mutual 2:3 or 3:4 MMR and at heliocentric distances within 18 AU (as favoured by recent studies), we found that the great majority of pre-formed Trojans would have been lost prior to Neptune's migration. This strengthens the case for the great bulk of the current Neptunian Trojan population having been captured during that migration.Comment: 17 pages, 2 figures, MNRAS (in press). Abstract slightly reduced in size, but in original form in the PDF fil

Planetary Migration and Extrasolar Planets in the 2/1 Mean-Motion Resonance

We analyze the possible relationship between the current orbital elements fits of known exoplanets in the 2/1 mean-motion resonance and the expected orbital configuration due to migration. It is found that, as long as the orbital decay was sufficiently slow to be approximated by an adiabatic process, all captured planets should be in apsidal corotations. In other words, they should show a simultaneous libration of both the resonant angle and the difference in longitudes of pericenter. We present a complete set of corotational solutions for the 2/1 commensurability, including previously known solutions and new results. Comparisons with observed exoplanets show that current orbital fits of three known planetary systems in this resonance are either consistent with apsidal corotations (GJ876 and HD82943) or correspond to bodies with uncertain orbits (HD160691). Finally, we discuss the applicability of these results as a test for the planetary migration hypothesis itself. If all future systems in this commensurability are found to be consistent with corotational solutions, then resonance capture of these bodies through planetary migration is a working hypothesis. Conversely, If any planetary pair is found in a different configuration, then either migration did not occur for those bodies, or it took a different form than currently believed.Comment: Submitted to MNRA

The influence of rifle carriage on the kinetics of human gait

The influence that rifle carriage has on human gait has received little attention in the published literature. Rifle carriage has two main effects, to add load to the anterior of the body and to restrict natural arm swing patterns. Kinetic data were collected from 15 male participants, with 10 trials in each of four experimental conditions. The conditions were: walking without a load (used as a control condition); carrying a lightweight rifle simulator, which restricted arm movements but applied no additional load; wearing a 4.4 kg diving belt, which allowed arms to move freely; carrying a weighted (4.4 kg) replica SA80 rifle. Walking speed was fixed at 1.5 m/s (+5%) and data were sampled at 400 Hz. Results showed that rifle carriage significantly alters the ground reaction forces produced during walking, the most important effects being an increase in the impact peak and mediolateral forces. This study suggests that these effects are due to the increased range of motion of the body’s centre of mass caused by the impeding of natural arm swing patterns. The subsequent effect on the potential development of injuries in rifle carriers is unknown

Pasireotide for the Medical Management of Feline Hypersomatotropism

BACKGROUND: Feline hypersomatotropism (HST) is a cause of diabetes mellitus in cats. Pasireotide is a novel multireceptor ligand somatostatin analog that improves biochemical control of humans with HST. HYPOTHESIS/OBJECTIVES: Pasireotide improves biochemical control of HST and diabetes mellitus in cats. ANIMALS: Hypersomatotropism was diagnosed in diabetic cats with serum insulin‐like growth factor‐1 (IGF‐1) concentration >1,000 ng/mL by radioimmunoassay and pituitary enlargement. METHODS: Insulin‐like growth factor 1 was measured and glycemic control assessed using a 12‐hour blood glucose curve on days 1 and 5. On days 2, 3, and 4, cats received 0.03 mg/kg pasireotide SC q12h. IGF‐1, insulin dose, and estimated insulin sensitivity (product of the area under the blood glucose curve [BGC] and insulin dose) were compared pre‐ and post treatment. Paired t‐tests or Wilcoxon signed rank tests were employed for comparison where appropriate; a linear mixed model was created to compare BGC results. RESULTS: Insulin‐like growth factor 1 decreased in all 12 cats that completed the study (median [range] day 1: 2,000 ng/mL [1,051–2,000] and day 5: 1,105 ng/mL [380–1,727], P = .002, Wilcoxon signed rank test). Insulin dose was lower on day 5 than on day 1 (mean reduction 1.3 [0–2.7] units/kg/injection, P = .003, paired t‐test). The product of insulin dose and area under the BGC was lower on day 5 than day 1 (difference of means: 1,912; SD, 1523; u × mg/dL × hours, P = .001; paired t‐test). No clinically relevant adverse effects were encountered. CONCLUSIONS: Short‐acting pasireotide rapidly decreased IGF‐1 in cats with HST and insulin‐dependent diabetes. The decrease in IGF‐1 was associated with increased insulin sensitivity

Dynamics of Jupiter Trojans during the 2:1 mean motion resonance crossing of Jupiter and Saturn

We study the dynamics of Jupiter Trojans in the early phase of the Solar system while the outer planets migrated due to their interaction with the planetesimal disk.Comment: 10 pages, 17 figure