Southern Ocean drives multidecadal atmospheric CO2 rise during Heinrich Stadials.

The last glacial period was punctuated by cold intervals in the North Atlantic region that culminated in extensive iceberg discharge events. These cold intervals, known as Heinrich Stadials, are associated with abrupt climate shifts worldwide. Here, we present CO2 measurements from the West Antarctic Ice Sheet Divide ice core across Heinrich Stadials 2 to 5 at decadal-scale resolution. Our results reveal multi-decadal-scale jumps in atmospheric CO2 concentrations within each Heinrich Stadial. The largest magnitude of change (14.0 ± 0.8 ppm within 55 ± 10 y) occurred during Heinrich Stadial 4. Abrupt rises in atmospheric CO2 are concurrent with jumps in atmospheric CH4 and abrupt changes in the water isotopologs in multiple Antarctic ice cores, the latter of which suggest rapid warming of both Antarctica and Southern Ocean vapor source regions. The synchroneity of these rapid shifts points to wind-driven upwelling of relatively warm, carbon-rich waters in the Southern Ocean, likely linked to a poleward intensification of the Southern Hemisphere westerly winds. Using an isotope-enabled atmospheric circulation model, we show that observed changes in Antarctic water isotopologs can be explained by abrupt and widespread Southern Ocean warming. Our work presents evidence for a multi-decadal- to century-scale response of the Southern Ocean to changes in atmospheric circulation, demonstrating the potential for dynamic changes in Southern Ocean biogeochemistry and circulation on human timescales. Furthermore, it suggests that anthropogenic CO2 uptake in the Southern Ocean may weaken with poleward strengthening westerlies today and into the future.

Fasting vs no fasting prior to catheterisation laboratory procedures: the SCOFF trial.

BACKGROUND AND AIMS: Current guidelines recommend 6 hours of solid food and 2 hours of clear liquid fasting for patients undergoing cardiac procedures with conscious sedation. There are no data to support this practice, and previous single centre studies support the safety of removing fasting requirements. The objective of this study was to determine the non-inferiority of a no fasting strategy to fasting prior to cardiac catheterisation procedures which require conscious sedation. METHODS: This is a multicentre, investigator-initiated, non-inferiority randomised trial conduced in Australia with a prospective open label blinded endpoint design. Patients referred for coronary angiography, percutaneous coronary intervention or cardiac implantable electronic device (CIED) related procedures were enrolled. Patients were randomised 1:1 to fasting as normal (6 hours solid food and 2 hours clear liquid) or no fasting requirements (encouraged to have regular meals but not mandated to do so). Recruitment occurred from 2022 to 2023. The primary outcome was a composite of aspiration pneumonia, hypotension, hyperglycaemia and hypoglycaemia assessed with a Bayesian approach. Secondary outcomes included patient satisfaction score, new ventilation requirement (non-invasive and invasive), new intensive care unit admission, 30-day readmission, 30-day mortality, 30-day pneumonia. RESULTS: 716 patients were randomised with 358 in each group. Those in the fasting arm had significantly longer solid food fasting (13.2 versus 3.0 hours, Bayes factor >100 indicating extreme evidence of difference) and clear liquid fasting times (7.0 versus 2.4 hours, Bayes factor >100). The primary composite outcome occurred in 19.1% of patients in the fasting arm and 12.0% of patients in the no fasting arm. The estimate of the mean posterior difference in proportions in the primary composite outcome was -5.2% (95% CI -9.6 to -0.9, ) favouring no fasting. This result confirms non-inferiority (posterior probability >99.5%) and superiority (posterior probability 99.1%) of no fasting for the primary composite outcome. The no fasting arm had improved patient satisfaction scores with a posterior mean difference of 4.02 points (95% CI 3.36 to 4.67, Bayes factor >100). Secondary outcome events were similar. CONCLUSIONS: In patients undergoing cardiac catheterisation and CIED related procedures, no fasting was non-inferior and superior to fasting for the primary composite outcome of aspiration pneumonia, hypotension, hyperglycaemia and hypoglycaemia. Patient satisfaction scores were significantly better with no fasting. This supports removing fasting requirements for patients undergoing cardiac catheterisation laboratory procedures that require conscious sedation.

Use of 3D Anorectal Ultrasonography in the Preoperative Assessment of Complex Anal Fistulas and Patterns of Healing, Failure, and Recurrence After Ligation of the Intersphincteric Fistula Tract (LIFT).

OBJECTIVES: To use three-dimensional anorectal ultrasonography (3D-US) to evaluate the outcome of ligation of the intersphincteric fistula tract (LIFT) in patients with crypto-glandular transsphincteric fistula and describing the patterns of healing, failure, and recurrence rate. METHODS: After classifying the fistula and determining the length of the sphincter muscle to be transected, the patients were submitted to LIFT. The accuracy of pre- and postoperative 3D-US with 360° endoprobe (16 MHz) with automatic scanning and clinical findings was evaluated against surgical findings. Three outcomes were considered: healing, failure (persistent anal fistula through the original external opening or intersphincteric), and recurrence (reappearance of the anal fistula). RESULTS: Sixty-three patients of both sexes were evaluated. The 3D-US assessment revealed primary healing in 50 (79.3%) patients, although in 6 (9.5%) cases healing was delayed and the cavity was without communication with the anal canal. The procedure failed in 9 (15.9%) and fistula recurred in 4 (6.3%), all of whom underwent a second surgery based on a new 3D-US, resulting in a 92.3% (12/13) healing rate on 3D-US. CONCLUSIONS: A 3D-US was found to be useful in the preoperative assessment of fistulas by quantifying the percentage of muscle to be transected, and in the postoperative assessment by identifying healing, types of failure, and recurrence. The 3D-US was accurate and consistent with surgical findings.

Impact of early postoperative blood glucose variability on serum endocan level in cardiac surgery patients: a sub study of the ENDOLUNG observational study.

BACKGROUND: Early postoperative glycemic variability is associated with worse outcome after cardiac surgery, but the underlying mechanisms remain unknown. This study aimed to describe the relationship between postoperative glycemic variability and endothelial function, as assessed by serum endocan level in cardiac surgery patients. METHODS: We performed a post hoc analysis of patients included in the single-center observational ENDOLUNG study. Adult patients who underwent planned isolated coronary artery bypass graft surgery were eligible. Postoperative glycemic variability was assessed by calculating the coefficient of variability (CV) of blood glucose measured within 24 (CV24) and 48 (CV48) hours after surgery. Serum endocan level was measured at 24 (Endocan24) and 48 (Endocan48) hours after surgery. Pearson's correlation coefficient with 95% confidence interval (95% CI) was calculated between CV24 and Endocan24, and between CV48 and Endocan48. RESULTS: Data from 177 patients were analyzed. Median CV24 and CV48 were 18% (range 7 to 39%) and 20% (range 7 to 35%) respectively. Neither CV48 nor CV24 were significantly correlated to Endocan48 and Endocan24 respectively (r (95% CI) = 0.150 (0.001 to 0.290; and r (95% CI) = 0.080 (-0.070 to 0.220), respectively). CONCLUSIONS: Early postoperative glycemic variability within 48 h after planned cardiac surgery does not appear to be correlated with postoperative serum endocan level. CLINICAL TRIAL REGISTRATION NUMBER: NCT02542423.

Impact of Internal Anal Sphincter Division on Continence Disturbance in Female Patients.

BACKGROUND: Few studies measured the pre- and postoperative anatomic and functional anal canal using 3-dimensional endoanal ultrasound and anal manometry and correlated sphincter division with fecal incontinence, severity, and function. OBJECTIVE: To assess the incidence of fecal incontinence in patients who underwent internal anal sphincter division for anal fissure or intersphincteric anal fistula and correlate severity of symptoms with percentage of divided muscle, anatomical measurements, and anal pressures. DESIGN: Prospective cohort study. SETTINGS: Colorectal surgery unit, tertiary referral center. PATIENTS: Patients underwent clinical assessment using the Cleveland Clinic Florida Fecal Incontinence score for severity of symptoms, manometry, and ultrasound. MAIN OUTCOMES MEASURES: Ultrasound measurements of length, percentage, and angle of divided internal anal sphincter, anterior external anal sphincter, posterior external anal sphincter plus puborectalis, and gap lengths. RESULTS: Sixty-three women (mean age, 44 years) were divided into 2 groups: 30 (48%) underwent fistulotomy for intersphincteric anal fistula and 33 (52%) underwent sphincterotomy for chronic anal fissure with high anal resting pressure. Forty-six percent experienced some measure of fecal incontinence after internal anal sphincter division. Incidence of fecal incontinence, severity of symptoms, and angle of the divided internal anal sphincter were similar between the groups. Length and percentage of the divided internal anal sphincter were significantly higher in the intersphincteric anal fistula. External anal sphincter and external anal sphincter plus puborectalis lengths were similar in both groups. Gap length was significantly longer in chronic anal fissures with high anal resting pressure. LIMITATIONS: Single-institution, exclusion of males. CONCLUSIONS: Fecal incontinence was reported in half of the patients who underwent internal anal sphincter division. Despite the greater length and percentage of internal anal sphincter division in patients who underwent fistulotomy, incidence and severity of fecal incontinence were similar in both groups. Three-dimensional endoanal ultrasound showed greater gap length in the sphincterotomy group, which may be functionally significant after the division of the shorter internal anal sphincter but with a similar impact on fecal incontinence in both groups. IMPACTO DE LA DIVISIN DEL ESFNTER ANAL INTERNO EN LA ALTERACIN DE LA CONTINENCIA EN PACIENTES DE SEXO FEMENINO: ANTECEDENTES:Pocos estudios han medido el canal anal anatómico y funcional antes y después de la cirugía mediante ecografía endoanal tridimensional y manometría anal, y correlacionado la división del esfínter con la incontinencia fecal, la gravedad y la función.OBJETIVO:Evaluar la incidencia de incontinencia fecal en pacientes sometidos a división del esfínter anal interno por fisura anal o fístula anal interesfinteriana, y correlacionar la gravedad de los síntomas con el porcentaje de músculo dividido, las medidas anatómicas y las presiones anales.DISEÑO:Estudio de cohorte prospectivo.AJUSTE:Unidad de cirugía colorrectal, centro de referencia de tercer nivel.PACIENTES:Pacientes sometidos a una evaluación clínica utilizando la puntuación de incontinencia fecal de Cleveland Clinic Florida para la gravedad de los síntomas, la manometría y la ecografía.PRINCIPALES MEDIDAS DE RESULTADO:Mediciones por ultrasonido de la longitud, el porcentaje y el ángulo del esfínter anal interno dividido y el esfínter anal externo anterior, el esfínter anal externo posterior más el puborrectal y las longitudes del espacio.RESULTADOS:Sesenta y tres mujeres (edad media, 44 años) se dividieron en 2 grupos: 30 (48%) sometidos a fistulotomía por fístula anal interesfinteriana y 33 (52%) sometidos a esfinterotomía por fisura anal crónica con alta presión anal en reposo. El 46% experimentó algún grado de incontinencia fecal después de la división del esfínter anal interno. La incidencia de incontinencia fecal, la gravedad de los síntomas y el ángulo del esfínter anal interno dividido fueron similares entre los grupos. La longitud y el porcentaje del esfínter anal interno dividido fueron significativamente mayores en la fístula anal interesfinteriana. Las longitudes del esfínter anal externo y del esfínter anal externo más el puborrectal fueron similares en ambos grupos. La longitud del espacio fue significativamente mayor en la fisura anal crónica con alta presión anal en reposo.LIMITACIONES:Institución única, exclusión de varones.CONCLUSIÓN:La incontinencia fecal se reportó en la mitad de los pacientes sometidos a división del esfínter anal interno. A pesar de la mayor longitud y porcentaje de división del esfínter anal interno en los pacientes sometidos a fistulotomía, la incidencia y gravedad de la incontinencia fecal fue similar en ambos grupos. La ecografía endoanal tridimensional mostró una mayor longitud del espacio en el grupo de esfinterotomía, lo que puede ser funcionalmente significativo después de la división del esfínter anal interno más corto, pero con un impacto similar en la incontinencia fecal en ambos grupos. (Traducción-Dr. Fidel Ruiz Healy ).

High Physical Activity Volume Is Associated With an Increase in the Calibre of the Lower Limb Veins Without Impact on Functional Discomfort: the VARISPORT Study.

OBJECTIVE: The relationship between physical activity and lower limb veins is complex. If a sedentary lifestyle is considered to be negative on lower limb veins, specific information on physical activity varicose vein volume is sparse, especially the effect of high physical activity volume. The main objective of the VARISPORT study was to evaluate lower limb veins (clinically, morphologically, and haemodynamically) and chronic venous disease symptoms in subjects exposed to high physical activity volume compared with a group of non-exposed subjects. METHODS: A cross sectional study compared a group of high exercise training volume volunteers (more than eight hours of uninterrupted vigorous intensity physical activity per week for more than six months: high physical activity volume group, HPAV group) with a volunteer control group matched for age, sex, and body mass index. Clinical examination was performed to determine the Clinical, Etiological, Anatomical, Pathophysiological (CEAP) classification of each subject and the Carpentier score was used to assess symptoms related to possible chronic venous disease. Duplex ultrasonography was used to assess vein diameters and reflux in the deep and superficial veins. RESULTS: One hundred and nineteen subjects were included in each group. The lower limb veins (deep and superficial) were significantly more dilated in the HPAV group. More reflux was found in the great saphenous veins and non-saphenous veins in the HPAV group. High physical activity volume was associated with a higher frequency of visible varicose veins (stage C2 of the CEAP classification), odds ratio 3.37 (95% confidence interval 1.66 - 7.25) without impact on functional discomfort (44 subjects with a Carpentier score ≥ 1 in each group). CONCLUSION: The VARISPORT study reported an increase in the calibre of the lower limb veins without impact on functional discomfort. Further studies are needed to determine whether these athletic veins are truly pathological varicose veins or simply an adaptation to high physical activity volumes.

Outer Hair Cell Glutamate Signaling through Type II Spiral Ganglion Afferents Activates Neurons in the Cochlear Nucleus in Response to Nondamaging Sounds.

Cochlear outer hair cells (OHCs) are known to uniquely participate in auditory processing through their electromotility, and like inner hair cells, are also capable of releasing vesicular glutamate onto spiral ganglion (SG) neurons: in this case, onto the sparse Type II SG neurons. However, unlike glutamate signaling at the inner hair cell-Type I SG neuron synapse, which is robust across a wide spectrum of sound intensities, glutamate signaling at the OHC-Type II SG neuron synapse is weaker and has been hypothesized to occur only at intense, possibly damaging sound levels. Here, we tested the ability of the OHC-Type II SG pathway to signal to the brain in response to moderate, nondamaging sound (80 dB SPL) as well as to intense sound (115 dB SPL). First, we determined the VGluTs associated with OHC signaling and then confirmed the loss of glutamatergic synaptic transmission from OHCs to Type II SG neurons in KO mice using dendritic patch-clamp recordings. Next, we generated genetic mouse lines in which vesicular glutamate release occurs selectively from OHCs, and then assessed c-Fos expression in the cochlear nucleus in response to sound. From these analyses, we show, for the first time, that glutamatergic signaling at the OHC-Type II SG neuron synapse is capable of activating cochlear nucleus neurons, even at moderate sound levels.SIGNIFICANCE STATEMENT Evidence suggests that cochlear outer hair cells (OHCs) release glutamate onto Type II spiral ganglion neurons only when exposed to loud sound, and that Type II neurons are activated by tissue damage. Knowing whether moderate level sound, without tissue damage, activates this pathway has functional implications for this fundamental auditory pathway. We first determined that OHCs rely largely on VGluT3 for synaptic glutamate release. We then used a genetically modified mouse line in which OHCs, but not inner hair cells, release vesicular glutamate to demonstrate that moderate sound exposure activates cochlear nucleus neurons via the OHC-Type II spiral ganglion pathway. Together, these data indicate that glutamate signaling at the OHC-Type II afferent synapse participates in auditory function at moderate sound levels.

Exploring Silent Speech Interfaces Based on Frequency-Modulated Continuous-Wave Radar.

Speech is our most natural and efficient form of communication and offers a strong potential to improve how we interact with machines. However, speech communication can sometimes be limited by environmental (e.g., ambient noise), contextual (e.g., need for privacy), or health conditions (e.g., laryngectomy), preventing the consideration of audible speech. In this regard, silent speech interfaces (SSI) have been proposed as an alternative, considering technologies that do not require the production of acoustic signals (e.g., electromyography and video). Unfortunately, despite their plentitude, many still face limitations regarding their everyday use, e.g., being intrusive, non-portable, or raising technical (e.g., lighting conditions for video) or privacy concerns. In line with this necessity, this article explores the consideration of contactless continuous-wave radar to assess its potential for SSI development. A corpus of 13 European Portuguese words was acquired for four speakers and three of them enrolled in a second acquisition session, three months later. Regarding the speaker-dependent models, trained and tested with data from each speaker while using 5-fold cross-validation, average accuracies of 84.50% and 88.00% were respectively obtained from Bagging (BAG) and Linear Regression (LR) classifiers, respectively. Additionally, recognition accuracies of 81.79% and 81.80% were also, respectively, achieved for the session and speaker-independent experiments, establishing promising grounds for further exploring this technology towards silent speech recognition.

Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies.

The past 2 decades have seen a revolution in our approach to therapeutic immunosuppression. We have moved from relying on broadly active traditional medications, such as prednisolone or methotrexate, toward more specific agents that often target a single receptor, cytokine, or cell type, using monoclonal antibodies, fusion proteins, or targeted small molecules. This change has transformed the treatment of many conditions, including rheumatoid arthritis, cancers, asthma, and inflammatory bowel disease, but along with the benefits have come risks. Contrary to the hope that these more specific agents would have minimal and predictable infectious sequelae, infectious complications have emerged as a major stumbling block for many of these agents. Furthermore, the growing number and complexity of available biologic agents makes it difficult for clinicians to maintain current knowledge, and most review articles focus on a particular target disease or class of agent. In this article, we review the current state of knowledge about infectious complications of biologic and small molecule immunomodulatory agents, aiming to create a single resource relevant to a broad range of clinicians and researchers. For each of 19 classes of agent, we discuss the mechanism of action, the risk and types of infectious complications, and recommendations for prevention of infection.

The Prevalence of Iron Deficiency in Atrial Fibrillation: Low Hanging Fruit?

Background and Objectives: Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. The relationship between AF and iron deficiency is poorly understood. Materials and Methods: We conducted an observational study investigating the prevalence of iron deficiency in those with AF. Iron deficiency was defined by the American College of Cardiology (ACC) criteria for iron deficiency in heart failure. Results: Of 134 eligible subjects, 81 (60.4%) met the ACC definition of iron deficiency in heart failure. Those who were iron deficient were more likely to be female (OR 1.876, p = 0.005), have a history of diabetes mellitus (OR 3.085, p = 0.001) a history of stroke (OR 3.147, p = 0.016), and have higher CHA2DS2-VASc (p ≤ 0.0001) and Charlson Comorbidity Index scores (CCI) (p = 0.007). Conclusions: The prevalence of iron deficiency in those with AF appears high and warrants evaluation in a prospective study.

Bayesian predictive probabilities: a good way to monitor clinical trials.

BACKGROUND: Bayesian methods, with the predictive probability (PredP), allow multiple interim analyses with interim posterior probability (PostP) computation, without the need to correct for multiple looks at the data. The objective of this paper was to illustrate the use of PredP by simulating a sequential analysis of a clinical trial. METHODS: We used data from the Laryngobloc trial that planned to include 480 patients to demonstrate the equivalence of success between a laryngoscopy performed with the Laryngobloc® device and a control device. A crossover Bayesian design was used. The success rates of the two laryngoscopy devices were compared. Interim analyses, computed from random numbers of subjects, were simulated. RESULTS: The PostP of equivalence rapidly reached the predefined bound of 0.95. The PredP computed with an equivalence margin of 10% reached the efficacy bound between 352 and 409 of the 480 included patients. If a frequentist analysis had been made on the basis of 217 out of 480 subjects, the study would have been prematurely stopped for equivalence. The PredP indicated that this result was nonetheless unstable and that the equivalence was, thus far, not guaranteed. CONCLUSIONS: Based on these interim analyses, we can conclude with a sufficiently high probability that the equivalence would have been met on the primary outcome before the predetermined end of this particular trial. If a Bayesian approach using PredP had been used, it would have allowed an early termination of the trial by reducing the calculated sample size by 15-20%.

Kawasaki Disease in the Australian Population: An Australian Tertiary Hospital Experience.

AIM: To describe the contemporary experience of Kawasaki Disease (KD) in a tertiary paediatric hospital. METHODS: This was a retrospective analysis of admissions with suspected/confirmed KD to John Hunter Children's Hospital from 1 January 2015 to 31 December 2016, with follow-up. Patients were stratified into classical, incomplete, unlikely and uncertain KD cohorts based on the 2004 American Heart Association (AHA) guidelines. RESULTS: Forty (40) patients had 45 admissions with suspected KD. Twenty-four (24) patients (60%) had complete and incomplete KD. Twenty-nine per cent (29%) (7/24) were not diagnosed at presentation. Thirty per cent (30%) (12/40) were incompletely assessed according to the AHA pathway. Seventy-one per cent (71%) of KD patients (17/24) were treated with aspirin and intravenous immunoglobulin. The incidence was 22-26 per 100,000 in children less than 5 years during the study period, higher compared to prior data. CONCLUSION: The diagnosis of KD remains challenging, with some children not diagnosed at the time of initial presentation. The increase in KD incidence is hypothesis generating and requires further investigation.

Involvement of the Hsp70/TLR4/IL-6 and TNF-α pathways in delayed-onset muscle soreness.

Delayed-onset muscle soreness (DOMS) is a very common condition in athletes and individuals not accustomed to physical activity that occurs after moderate/high-intensity exercise sessions. The activation of microglial Toll-like receptor 4 (TLR4) in the spinal cord has been described to be important for the induction and maintenance of persistent pain. Based on that, we hypothesize that 70 kilodalton heat-shock protein (Hsp70), a mediator released by exercise, could activate microglial TLR4 in the spinal cord, releasing proinflammatory cytokines and contributing to the start of DOMS. In fact, we found that the knockout of TLR4, myeloid differentiation primary response 88 (MyD88), interleukin-6 (IL-6), or both tumor necrosis factor-α (TNF-α) receptor 1 and TNF-α receptor 2 in mice prevented the development of DOMS following acute aerobic exercise in contrast to the findings in male C57BL/6 wild-type mice. Furthermore, DOMS in exercised wild-type mice was also prevented after pre-treatment with microglia inhibitor, TLR4 antagonist, and anti-Hsp70 antibody. During exercise-induced DOMS, Hsp70 mRNA, TLR4 mRNA, and protein levels, as well as Iba-1 (a microglial marker), IL-6, and TNF-α protein levels, were increased in the muscle and/or spinal cord. Together, these findings suggest that Hsp70 released during exercise-induced DOMS activates the microglial TLR4/IL-6/TNF-α pathway in the spinal cord. Thus, the blockade of TLR4 activation may be a new strategy to prevent the development of DOMS before intense exercise.

Clinical trials for the prevention and treatment of COVID-19: current state of play.

Since coronavirus disease 2019 (COVID-19) emerged in Wuhan, China in December 2019 and spread around the world, over 1100 clinical studies have been registered globally on clinical trials registries, including over 500 randomised controlled trials. Such rapid development and launch of clinical trials is impressive but presents challenges, including the potential for duplication and competition. There is currently no known effective treatment for COVID-19. In order to focus on those studies most likely to influence clinical practice, we summarise the 31 currently registered randomised trials with a target sample size of at least 1000 participants. We have grouped these trials into four categories: prophylaxis; treatment of outpatients with mild COVID-19; treatment of hospitalised patients with moderate COVID-19; and treatment of hospitalised patients with moderate or severe disease. The most common therapeutic agent being trialled currently is hydroxychloroquine (24 trials with potential sample size of over 25 000 participants), followed by lopinavir-ritonavir (seven trials) and remdesevir (five trials) There are many candidate drugs in pre-clinical and early phase development, and these form a pipeline for future large clinical trials if current candidate therapies prove ineffective or unsafe.

Theory and practical use of Bayesian methods in interpreting clinical trial data: a narrative review.

The critical reading of scientific articles is necessary for the daily practice of evidence-based medicine. Rigorous comprehension of statistical methods is essential, as reflected by the extensive use of statistics in the biomedical literature. In contrast to the customary frequentist approach, which never uses or gives the probability of a hypothesis, Bayesian theory uses probabilities for both hypotheses and data. This statistical approach is increasingly used for analyses of clinical trial data and for applied machine learning. The aim of this review is to compare general Bayesian concepts with frequentist methods to facilitate a better understanding of Bayesian theory for readers who are not familiar with this approach. The review is intended to be used in combination with a checklist we have devised for reading reports analysed by Bayesian methods. We compare and contrast the different approaches of Bayesian vs frequentist statistical methods by considering data from a clinical trial that lends itself to this comparative approach.

A consensus checklist to help clinicians interpret clinical trial results analysed by Bayesian methods.

INTRODUCTION: In the context of an increasing number of publications of trial data analysed by Bayesian methods, clinicians need support to better understand Bayesian statistical methods. The existing checklists are intended for people who already know these methods. We aimed to establish and validate a checklist that contains a group of items considered crucial in interpreting the results of a phase III RCT analysed with Bayesian methods. METHODS: A team of biostatisticians created a checklist of previously reported items and additional items identified from a literature review. Using three different articles in three rounds, the items were then validated by residents in anaesthesiology with no skills in statistics. RESULTS: Based on an initial item list, three rounds led to a consensus checklist. Eleven items were considered important information to be specified for understanding the validity of the results. Of these, three were considered essential: specification of the prior, source of the prior (when prior is informative), and the effect size point estimate with its credible interval. CONCLUSION: The checklist can help clinicians interpret the results of a phase III randomised clinical trial analysed by Bayesian methods, even clinicians with no particular knowledge of statistics, to ensure that the major elements of the statistical section are present and valid. Care should be taken in interpreting the results of a trial analysed by Bayesian methods that are not reported with these three essential items because the validity of the results cannot be established.

Contemporary trends in stroke complicating cardiac catheterisation.

BACKGROUND: Stroke remains an important complication of diagnostic cardiac catheterisation and percutaneous coronary intervention and is associated with high rates of in-hospital mortality. AIMS: To evaluate the incidence of stroke over a 10-year period and assess the long-term influence of stroke following cardiac catheterisation and PCI on functional outcomes, based on modified Rankin score and mortality. METHODS: The study was performed using a case-control design in a single tertiary referral centre. Patients were identified by correlating those patients undergoing cardiac catheterisation between October 2006 and December 2016 with patients who underwent neuroimaging within 7 days to identify possible cases of suspected stroke or transient ischaemic attack. RESULTS: A total of 21 510 patients underwent cardiac catheterisation during the study period. Sixty (0.28%) patients experienced stroke or transient ischaemic attack. Compared to control patients, those who did experience cerebral ischaemic events were older (70.5 vs 64 years; P < 0.001), with higher rates of atrial fibrillation, hypertension and diabetes mellitus. Stroke complicating cardiac catheterisation was associated with an increased risk of readmission, with a significantly higher hazard of readmission for stroke noted. Despite minimal functional impairment based on modified Rankin score, stroke was associated with a significant risk of early and cumulative mortality. Stroke incidence remained stable over the study period despite changes in procedural practice. CONCLUSIONS: The incidence and functional severity of stroke remains low despite evolving procedural practice with a stable incidence over time despite changes in procedural practice; however, post-procedural stroke confirms an increased mortality hazard.

QA-kNN: Indoor Localization Based on Quartile Analysis and the kNN Classifier for Wireless Networks.

Considering the variation of the received signal strength indicator (RSSI) in wireless networks, the objective of this study is to investigate and propose a method of indoor localization in order to improve the accuracy of localization that is compromised by RSSI variation. For this, quartile analysis is used for data pre-processing and the k-nearest neighbors (kNN) classifier is used for localization. In addition to the tests in a real environment, simulations were performed, varying many parameters related to the proposed method and the environment. In the real environment with reference points of 1.284 density per unit area (RPs/m2), the method presents zero-mean error in the localization in test points (TPs) coinciding with the RPs. In the simulated environment with a density of 0.327 RPs/m2, a mean error of 0.490 m for the localization of random TPs was achieved. These results are important contributions and allow us to conclude that the method is promising for locating objects in indoor environments.

Calcitriol loading before total parathyroidectomy with autotransplant in patients with end-stage kidney disease: does it prevent postoperative hypocalcaemia?

BACKGROUND: Hungry bone syndrome (HBS) is one of the most serious complications following parathyroidectomy for severe hyperparathyroidism. There is a lack of literature informing the treatment and risk factors for this condition and the ideal pre-operative strategy for prevention. AIMS: The primary aims were to examine the incidence of HBS with pre-operative calcitriol loading for 10 days and to determine the risk factors for HBS. The secondary aims were to determine the rate of intravenous calcium replacement in those with HBS and to assess whether cinacalcet removal has increased rates of parathyroidectomy in the end-stage kidney disease population. METHODS: We performed a retrospective study from 2011 to 2018 on 45 patients with end-stage kidney disease undergoing total parathyroidectomy with autotransplantation for severe hyperparathyroidism. This was based at the John Hunter and Newcastle Private Hospitals in New South Wales. RESULTS: 28.3% of patients with calcitriol loading undergoing parathyroidectomy fulfilled criteria for HBS. Pre-operative variables that were associated with HBS were elevated parathyroid hormone (P = 0.028) and longer duration of renal replacement therapy (P = 0.033). Rates of total parathyroidectomy were higher after the removal of calcimimetics from the Pharmaceutical Benefits Scheme (P = 0.0024). CONCLUSIONS: HBS remains a common complication of parathyroidectomy, even with prolonged high-dose calcitriol loading. This emphasises the need for further trials investigating other targeted therapies, such as bisphosphonates, to prevent HBS. Those most at risk of HBS are patients with high bone turnover and prolonged renal replacement therapy.