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Opioid-free anaesthesia may enhance postoperative recovery by reducing opioid-related side effects such as nausea, hyperalgesia or tolerance. The objective was to investigate the impact of multimodal opioid-free general anaesthesia on postoperative nausea, vomiting, pain and morphine consumption compared to the traditional opioid-based approach. This study was conducted as a prospective parallel-group randomised controlled trial. Perioperative Care. 152 adult women undergoing elective inpatient gynaecological laparoscopy. Patients were randomly assigned for opioid-free anaesthesia (Group OF) with dexmedetomidine, esketamine and sevoflurane or to have opioid-based anaesthesia (Group C) with sufentanil and sevoflurane. Primary outcome was the occurrence of nausea within 24 h after surgery. Patients were assessed for the incidence and severity of PONV, postoperative pain and morphine consumption and recovery characteristics. Patients in both groups had comparable clinical and surgical data. 69.7% of patients in the control group and 68.4% of patients in the opioid-free group met the primary endpoint (OR 1.06, 95% Confidence Interval (CI) (0.53; 2.12) p = 0.86). The incidence of clinically important PONV defined by the PONV impact scale was 8.1% (Group C) vs 10.5% (OF); p = 0.57). Antiemetic requirements, pain scores and morphine consumption were equivalent in both groups. Postoperative sedation was significantly increased in group OF (p < 0.001), and the median length of stay at the post-anaesthesia care unit was 69.0 min (46.5–113.0) vs 50.0 (35.3–77.0) minutes in the control group (p < 0.001). Opioid-free multimodal general anaesthesia is feasible but did not decrease the incidence of PONV, or reduce pain scores and morphine consumption compared to an opioid-containing anaesthetic regimen. •This trial assessed opioid-free anaesthesia in comparison to opioid-based anaesthesia for gynaecological laparoscopy.•Both study groups did not differ with respect to postoperative nausea and vomiting, pain or morphine consumption.•Multimodal general anaesthesia was associated with an increased time to discharge from the post-anaesthesia care unit.

Background Simulation has become integral to the training of both undergraduate medical students and medical professionals. Due to the increasing degree of realism and range of features, the latest mannequins are referred to as high-fidelity simulators. Whether increased realism leads to a general improvement in trainees’ outcomes is currently controversial and there are few data on the effects of these simulators on participants’ personal confidence and self-assessment. Methods One-hundred-and-thirty-five fourth-year medical students were randomly allocated to participate in either a high- or a low-fidelity simulated Advanced Life Support training session. Theoretical knowledge and self-assessment pre- and post-tests were completed. Students’ performance in simulated scenarios was recorded and rated by experts. Results Participants in both groups showed a significant improvement in theoretical knowledge in the post-test as compared to the pre-test, without significant intergroup differences. Performance, as assessed by video analysis, was comparable between groups, but, unexpectedly, the low-fidelity group had significantly better results in several sub-items. Irrespective of the findings, participants of the high-fidelity group considered themselves to be advantaged, solely based on their group allocation, compared with those in the low-fidelity group, at both pre- and post-self-assessments. Self-rated confidence regarding their individual performance was also significantly overrated. Conclusion The use of high-fidelity simulation led to equal or even worse performance and growth in knowledge as compared to low-fidelity simulation, while also inducing undesirable effects such as overconfidence. Hence, in this study, it was not beneficial compared to low-fidelity, but rather proved to be an adverse learning tool.

Objective To examine whether, according to the conclusions of a 2000 systematic review with meta-analysis on interventions to prevent pain from propofol injection that provided a research agenda to guide further research on the topic, subsequently published trials were more often optimally blinded, reported on children, and used the most efficacious intervention as comparator; and to check whether the number of new trials published each year had decreased and whether the designs of trials that cited the review differed from those that did not.Study design Systematic review comparing old trials (published before, and included in, the review) with new trials (published afterwards).Data sources Medline, Cochrane, Embase, and bibliographies to January 2013.Eligibility criteria for study selection Randomised studies testing any intervention to prevent pain from propofol injection in humans.Results 136 new trials (19 778 patients) were retrieved. Compared with the 56 old trials (6264 patients), the proportion of optimally blinded trials had increased from 10.7% to 38.2% (difference 27.5%, 95% confidence interval 16.0% to 39.0%, P<0.001), and the proportion of trials that used the most efficacious intervention as comparator had increased from 12.5% to 27.9% (difference 15.4%, 4.0% to 26.9%, P=0.022). The proportion of paediatric trials had increased from 5.4% to 12.5%, although this was not significant (difference 7.1%, −1.0% to 15.2%, P=0.141). The number of new trials published each year was significantly higher (median number/year 12 (range 7-20) v 2.5 (0-9), P<0.001) with no obvious decreasing trend. 72.8% (n=99) of the new trials cited the review, with their designs similar to trials not citing the review. Only 36.0% (n=49) of the new trials were considered clinically relevant since they used the most efficacious intervention as comparator or included a paediatric population.Conclusions The impact of the systematic review on the design of subsequent research was low. There was an improvement in the reporting of optimal blinding procedures and a tendency towards an increase in the proportion of paediatric trials. The most efficacious intervention was more often chosen as comparator but remained marginally used, and the number of trials published per year had not decreased. The use of systematic reviews should be encouraged to inform rational, and thus ethical, trial design and improve the relevance of new research.

Simulation-based teaching (SBT) is increasingly used in medical education. As an alternative to other teaching methods there is a lack of evidence concerning its efficacy. The aim of this study was to evaluate the potency of SBT in anesthesia in comparison to problem-based discussion (PBD) with students in a randomized controlled setting. Thirty-three fourth-year medical students attending a curricular anesthesiology course were randomly allocated to either a session of SBT or a session of PBD on an emergency induction method. Ten days later all students underwent examination in a simulator. The performance of each student was evaluated by weighted tasks, established according to a modified Delphi process. Confidence and a multiple-choice questionnaire were additionally performed pre- and post-intervention. A total of 32 students completed the study. Participants in the SBT group presented with significantly higher self-assessment scores after the intervention than students in the PBD group. However, students in the SBT group achieved only slightly and statistically insignificantly higher scores in the theoretical and simulator examination ( p  > 0.05) with only a moderate effect size of d  = 0.52. The current study demonstrates that both PBD and SBT lead to comparable short-term outcomes in theoretical knowledge and clinical skills. However, undesirably, SBT students overrated their anticipated clinical abilities and knowledge improvement.

ObjectivesTo study whether systematic reviewers apply procedures to counter-balance some common forms of research malpractice such as not publishing completed research, duplicate publications, or selective reporting of outcomes, and to see whether they identify and report misconduct.DesignCross-sectional analysis of systematic reviews and survey of their authors.Participants118 systematic reviews published in four journals (Ann Int Med, BMJ, JAMA, Lancet), and the Cochrane Library, in 2013.Main outcomes and measuresNumber (%) of reviews that applied procedures to reduce the impact of: (1) publication bias (through searching of unpublished trials), (2) selective outcome reporting (by contacting the authors of the original studies), (3) duplicate publications, (4) sponsors’ and (5) authors’ conflicts of interest, on the conclusions of the review, and (6) looked for ethical approval of the studies. Number (%) of reviewers who suspected misconduct are reported. The procedures applied were compared across journals.Results80 (68%) reviewers confirmed their data. 59 (50%) reviews applied three or more procedures; 11 (9%) applied none. Unpublished trials were searched in 79 (66%) reviews. Authors of original studies were contacted in 73 (62%). Duplicate publications were searched in 81 (69%). 27 reviews (23%) reported sponsors of the included studies; 6 (5%) analysed their impact on the conclusions of the review. Five reviews (4%) looked at conflicts of interest of study authors; none of them analysed their impact. Three reviews (2.5%) looked at ethical approval of the studies. Seven reviews (6%) suspected misconduct; only 2 (2%) reported it explicitly. Procedures applied differed across the journals.ConclusionsOnly half of the systematic reviews applied three or more of the six procedures examined. Sponsors, conflicts of interest of authors and ethical approval remain overlooked. Research misconduct is sometimes identified, but rarely reported. Guidance on when, and how, to report suspected misconduct is needed.

Single-photon emission computed tomography (SPECT) using 3-[(123)I]-iodo-L-alpha-methyltyrosine ([(123)I]-IMT) and positron emission tomography (PET) using 2-[(18)F]-fluoro-2-deoxy-D-glucose ([(18)F]-FDG) are valuable tools for the distinction between viable tumor and radionecrosis in patients receiving radiotherapy for high-grade gliomas. However, to date, little is known about the early effects of radiation on [(123)I]-IMT and [(18)F]-FDG uptake in gliomas.BACKGROUNDSingle-photon emission computed tomography (SPECT) using 3-[(123)I]-iodo-L-alpha-methyltyrosine ([(123)I]-IMT) and positron emission tomography (PET) using 2-[(18)F]-fluoro-2-deoxy-D-glucose ([(18)F]-FDG) are valuable tools for the distinction between viable tumor and radionecrosis in patients receiving radiotherapy for high-grade gliomas. However, to date, little is known about the early effects of radiation on [(123)I]-IMT and [(18)F]-FDG uptake in gliomas.To determine the early effects of irradiation on [(123)I]-IMT and [(18)F]-FDG uptake in gliomas, in vitro studies were performed using rat C6 glioma cells. The glioma cells were irradiated with 20 Gy which is a common dose applied to patients receiving intraoperative radiotherapy. Subsequently, the early kinetics of [(123)I]-IMT and [(18)F]-FDG uptake in glioma cells were monitored for 3 days.MATERIAL AND METHODSTo determine the early effects of irradiation on [(123)I]-IMT and [(18)F]-FDG uptake in gliomas, in vitro studies were performed using rat C6 glioma cells. The glioma cells were irradiated with 20 Gy which is a common dose applied to patients receiving intraoperative radiotherapy. Subsequently, the early kinetics of [(123)I]-IMT and [(18)F]-FDG uptake in glioma cells were monitored for 3 days.Micromorphometric examinations of the irradiated glioma cells revealed that about 25% of the viable cells transformed into giant cells. [(123)I]-IMT uptake per 10(5) viable glioma cells was unchanged on the 1st day post irradiation, but showed a significant increase on the 2nd and 3rd day following radiotherapy (p < 0.01). In addition, there was a moderate increase in [(18)F]- FDG accumulation per 10(5) viable glioma cells during the first 3 days after irradiation (p < 0.05). The maximum increase in early [(123)I]-IMT uptake 1 h after application surpassed that of [(18)F]-FDG (p < 0.01).RESULTSMicromorphometric examinations of the irradiated glioma cells revealed that about 25% of the viable cells transformed into giant cells. [(123)I]-IMT uptake per 10(5) viable glioma cells was unchanged on the 1st day post irradiation, but showed a significant increase on the 2nd and 3rd day following radiotherapy (p < 0.01). In addition, there was a moderate increase in [(18)F]- FDG accumulation per 10(5) viable glioma cells during the first 3 days after irradiation (p < 0.05). The maximum increase in early [(123)I]-IMT uptake 1 h after application surpassed that of [(18)F]-FDG (p < 0.01).Rat C6 glioma cells show an early increase in [(123)I]-IMT and [(18)F]-FDG uptake following irradiation which may be partly due to giant cell formation. These data suggest that [(123)I]-IMT SPECT and [(18)F]-FDG PET may be promising procedures for the early prediction of the therapeutic response of gliomas to radiotherapy.CONCLUSIONRat C6 glioma cells show an early increase in [(123)I]-IMT and [(18)F]-FDG uptake following irradiation which may be partly due to giant cell formation. These data suggest that [(123)I]-IMT SPECT and [(18)F]-FDG PET may be promising procedures for the early prediction of the therapeutic response of gliomas to radiotherapy.

Single-photon emission computed tomography (SPECT) using 3-[(123)I]-iodo-L-alpha-methyltyrosine ([(123)I]-IMT) and positron emission tomography (PET) using 2-[(18)F]-fluoro-2-deoxy-D-glucose ([(18)F]-FDG) are valuable tools for the distinction between viable tumor and radionecrosis in patients receiving radiotherapy for high-grade gliomas. However, to date, little is known about the early effects of radiation on [(123)I]-IMT and [(18)F]-FDG uptake in gliomas. To determine the early effects of irradiation on [(123)I]-IMT and [(18)F]-FDG uptake in gliomas, in vitro studies were performed using rat C6 glioma cells. The glioma cells were irradiated with 20 Gy which is a common dose applied to patients receiving intraoperative radiotherapy. Subsequently, the early kinetics of [(123)I]-IMT and [(18)F]-FDG uptake in glioma cells were monitored for 3 days. Micromorphometric examinations of the irradiated glioma cells revealed that about 25% of the viable cells transformed into giant cells. [(123)I]-IMT uptake per 10(5) viable glioma cells was unchanged on the 1st day post irradiation, but showed a significant increase on the 2nd and 3rd day following radiotherapy (p < 0.01). In addition, there was a moderate increase in [(18)F]- FDG accumulation per 10(5) viable glioma cells during the first 3 days after irradiation (p < 0.05). The maximum increase in early [(123)I]-IMT uptake 1 h after application surpassed that of [(18)F]-FDG (p < 0.01). Rat C6 glioma cells show an early increase in [(123)I]-IMT and [(18)F]-FDG uptake following irradiation which may be partly due to giant cell formation. These data suggest that [(123)I]-IMT SPECT and [(18)F]-FDG PET may be promising procedures for the early prediction of the therapeutic response of gliomas to radiotherapy.

The ratios of strong rest-frame optical emission lines are the dominant indicator of metallicities in high-redshift galaxies. Since typical strong-line based metallicity indicators are calibrated on auroral lines at \\(z=0\\), their applicability for galaxies in the distant Universe is unclear. In this paper, we make use of mock emission line data from cosmological simulations to investigate the calibration of rest-frame optical emission lines as metallicity indicators at high redshift. Our model, which couples the SIMBA cosmological galaxy formation simulation with cloudy photoionization calculations, includes contributions from HII regions, post-AGB stars and Diffuse Ionized Gas (DIG). We find mild redshift evolution in the 12 indicators that we study, which implies that the dominant physical properties that evolve in our simulations do have a discernible impact on the metallicity calibrations at high redshifts. When comparing our calibrations with high redshift auroral line observations from James Webb Space Telescope we find a slight offset between our model results and the observations and find that a higher ionization parameter at high redshifts can be one of the possible explanations. We explore the physics that drives the shapes of strong-line metallicity relationships and propose calibrations for hitherto unexplored low-metallicity regimes. Finally, we study the contribution of DIG to total line fluxes. We find that the contribution of DIG increases with metallicity at z \\(\\sim\\) 0 for singly ionized oxygen and sulfur lines and can be as high as 70% making it crucial to include their contribution when modeling nebular emission.

We present a statistical study of 180 dust continuum sources identified in 33 massive cluster fields by the ALMA Lensing Cluster Survey (ALCS) over a total of 133 arcmin\\(^{2}\\) area, homogeneously observed at 1.2 mm. ALCS enables us to detect extremely faint mm sources by lensing magnification, including near-infrared (NIR) dark objects showing no counterparts in existing {\\it Hubble Space Telescope} and {\\it Spitzer} images. The dust continuum sources belong to a blind sample (\\(N=141\\)) with S/N \\(\\gtrsim\\) 5.0 (a purity of \\(>\\) 0.99) or a secondary sample (\\(N=39\\)) with S/N= \\(4.0-5.0\\) screened by priors. With the blind sample, we securely derive 1.2-mm number counts down to \\(\\sim7\\) \\(\\mu\\)Jy, and find that the total integrated 1.2mm flux is 20.7\\(^{+8.5}_{-6.5}\\) Jy deg\\(^{-2}\\), resolving \\(\\simeq\\) 80 % of the cosmic infrared background light. The resolved fraction varies by a factor of \\(0.6-1.1\\) due to the completeness correction depending on the spatial size of the mm emission. We also derive infrared (IR) luminosity functions (LFs) at \\(z=0.6-7.5\\) with the \\(1/V_{\\rm max}\\) method, finding the redshift evolution of IR LFs characterized by positive luminosity and negative density evolution. The total (=UV+IR) cosmic star-formation rate density (SFRD) at \\(z>4\\) is estimated to be \\(161^{+25}_{-21}\\) % of the established measurements, which were almost exclusively based on optical\\(-\\)NIR surveys. Although our general understanding of the cosmic SFRD is unlikely to change beyond a factor of 2, these results add to the weight of evidence for an additional (\\(\\approx 60\\) %) SFRD component contributed by the faint-mm population, including NIR dark objects.

We report the detection of an ultra-bright fast radio burst (FRB) from a modest, 3.4-day pilot survey with the Australian Square Kilometre Array Pathfinder. The survey was conducted in a wide-field fly's-eye configuration using the phased-array-feed technology deployed on the array to instantaneously observe an effective area of \\(160\\) deg\\(^2\\), and achieve an exposure totaling \\(13200\\) deg\\(^2\\) hr. We constrain the position of FRB 170107 to a region \\(8'\\times8'\\) in size (90% containment) and its fluence to be \\(58\\pm6\\) Jy ms. The spectrum of the burst shows a sharp cutoff above \\(1400\\) MHz, which could be either due to scintillation or an intrinsic feature of the burst. This confirms the existence of an ultra-bright (\\(>20\\) Jy ms) population of FRBs.