Machine learning approach for ambient-light-corrected parameters and the Pupil Reactivity (PuRe) score in smartphone-based pupillometry.

Introduction: The pupillary light reflex (PLR) is the constriction of the pupil in response to light. The PLR in response to a pulse of light follows a complex waveform that can be characterized by several parameters. It is a sensitive marker of acute neurological deterioration, but is also sensitive to the background illumination in the environment in which it is measured. To detect a pathological change in the PLR, it is therefore necessary to separate the contributions of neuro-ophthalmic factors from ambient illumination. Illumination varies over several orders of magnitude and is difficult to control due to diurnal, seasonal, and location variations. Methods and results: We assessed the sensitivity of seven PLR parameters to differences in ambient light, using a smartphone-based pupillometer (AI Pupillometer, Solvemed Inc.). Nine subjects underwent 345 measurements in ambient conditions ranging from complete darkness (<5 lx) to bright lighting (≲10,000 lx). Lighting most strongly affected the initial pupil size, constriction amplitude, and velocity. Nonlinear models were fitted to find the correction function that maximally stabilized PLR parameters across different ambient light levels. Next, we demonstrated that the lighting-corrected parameters still discriminated reactive from unreactive pupils. Ten patients underwent PLR testing in an ophthalmology outpatient clinic setting following the administration of tropicamide eye drops, which rendered the pupils unreactive. The parameters corrected for lighting were combined as predictors in a machine learning model to produce a scalar value, the Pupil Reactivity (PuRe) score, which quantifies Pupil Reactivity on a scale 0-5 (0, non-reactive pupil; 0-3, abnormal/"sluggish" response; 3-5, normal/brisk response). The score discriminated unreactive pupils with 100% accuracy and was stable under changes in ambient illumination across four orders of magnitude. Discussion: This is the first time that a correction method has been proposed to effectively mitigate the confounding influence of ambient light on PLR measurements, which could improve the reliability of pupillometric parameters both in pre-hospital and inpatient care settings. In particular, the PuRe score offers a robust measure of Pupil Reactivity directly applicable to clinical practice. Importantly, the formulae behind the score are openly available for the benefit of the clinical research community.

Deep learning on pre-procedural computed tomography and clinical data predicts outcome following stroke thrombectomy.

BACKGROUND: Deep learning using clinical and imaging data may improve pre-treatment prognostication in ischemic stroke patients undergoing endovascular thrombectomy (EVT). METHODS: Deep learning models were trained and tested on baseline clinical and imaging (CT head and CT angiography) data to predict 3-month functional outcomes in stroke patients who underwent EVT. Classical machine learning models (logistic regression and random forest classifiers) were constructed to compare their performance with the deep learning models. An external validation dataset was used to validate the models. The MR PREDICTS prognostic tool was tested on the external validation set, and its performance was compared with the deep learning and classical machine learning models. RESULTS: A total of 975 patients (550 men; mean±SD age 67.5±15.1 years) were studied with 778 patients in the model development cohort and 197 in the external validation cohort. The deep learning model trained on baseline CT and clinical data, and the logistic regression model (clinical data alone) demonstrated the strongest discriminative abilities for 3-month functional outcome and were comparable (AUC 0.811 vs 0.817, Q=0.82). Both models exhibited superior prognostic performance than the other deep learning (CT head alone, CT head, and CT angiography) and MR PREDICTS models (all Q<0.05). CONCLUSIONS: The discriminative performance of deep learning for predicting functional independence was comparable to logistic regression. Future studies should focus on whether incorporating procedural and post-procedural data significantly improves model performance.

The aetiology of fracture and nonunion in the hook of the hamate.

Fractures of the hook of the hamate are traditionally thought to be caused by direct trauma. A review of the anatomy and function of the hamate hook suggests that fracture is more likely as a result of a fatigue response that develops in the hook from repetitive load applied by the adjacent deep flexor tendons. Additional vascular compromise, from direct pressure of the tendons on critical local vessels, reduces blood flow leading to both mechanical and vascular effects that create pathological osseous change and weakening. These changes are likely to predispose to stress fracture and nonunion in repetitive gripping activities and are consistent with radiological findings.

Penumbral cooling in ischemic stroke with intraarterial, intravenous or active conductive head cooling: A thermal modeling study.

In ischemic stroke, selectively cooling the ischemic penumbra might lead to neuroprotection while avoiding systemic complications. Because penumbral tissue has reduced cerebral blood flow and in vivo brain temperature measurement remains challenging, the effect of different methods of therapeutic hypothermia on penumbral temperature are unknown. We used the COMSOL Multiphysics® software to model a range of cases of therapeutic hypothermia in ischemic stroke. Four ischemic stroke models were developed with ischemic core and/or penumbra volumes between 33-300 mL. Four experiments were performed on each model, including no cooling, and intraarterial, intravenous, and active conductive head cooling. The steady-state temperature of the non-ischemic brain, ischemic penumbra, and ischemic core without cooling was 37.3 °C, 37.5-37.8 °C, and 38.9-39.4 °C respectively. Intraarterial, intravenous and active conductive head cooling reduced non-ischemic brain temperature by 4.3 °C, 2.1 °C, and 0.7-0.8 °C respectively. Intraarterial, intravenous and head cooling reduced the temperature of the ischemic penumbra by 3.9-4.3 °C, 1.9-2.1 °C, and 1.2-3.4 °C respectively. Active conductive head cooling was the only method to selectively reduce penumbral temperature. Clinical studies that measure brain temperature in ischemic stroke patients undergoing therapeutic hypothermia are required to validate these hypothesis-generating findings.

What differences exist between the lead and trail wrist in extensor carpi ulnaris activity and golf swing joint kinematics in sub-elite golfers?

This study assessed the lead and trail arm peak and average extensor carpi ulnaris (ECU) muscle activity in association with tri-planar angular velocities of the lead and trail wrists during the golf swing. Fifteen sub-elite, male right-handed golfers (Mage = 34.7 years ±13.3, Mhandicap = 1.5 ± 2.2) were recruited to execute five shots each with their pitching wedge, 7-iron and driver clubs in an indoor golf simulator. Surface electromyography (EMG) sensors were placed over the ECU muscle belly and inertial measurement unit sensors were placed bi-laterally on the distal forearm and dorsum of the hand. There was a statistically greater recruitment of the trail ECU muscle during the downswing (p < 0.001) for all clubs. The lead ECU muscle was recruited more during the backswing (p < 0.001) and follow through (p < 0.024) phases. There were statistically different tri-planar movement patterns between the lead and trail wrist throughout all three phases of the golf swing. No significant relationships were found between downswing EMG data and clubhead kinematics at impact. In conclusion, differing wrist kinematics and associated muscle activity may contribute to the asymmetrical injury pattern seen clinically.

Using days alive and out of hospital to measure surgical outcomes in New Zealand: a cross-sectional study.

OBJECTIVES: To measure differences at various deciles in days alive and out of hospital to 90 days (DAOH90) and explore its utility for identifying outliers of performance among district health boards (DHBs). METHODS: Days in hospital and mortality within 90 days of surgery were extracted by linking data from the New Zealand National Minimum Data Set and the births and deaths registry between 1 January 2011 and 31 December 2021 for all adults in New Zealand undergoing acute laparotomy (AL-a relatively high-risk group), elective total hip replacement (THR-a medium risk group) or lower segment caesarean section (LSCS-a low-risk group). DAOH90 was calculated without censoring to zero in cases of mortality. For each DHB, direct risk standardisation was used to adjust for potential confounders and presented in deciles according to baseline patient risk. The Mann-Whitney U test assessed overall DAOH90 differences between DHBs, and comparisons are presented between selected deciles of DAOH90 for each operation. RESULTS: We obtained national data for 35 175, 52 032 and 117 695 patients undergoing AL, THR and LSCS procedures, respectively. We have demonstrated that calculating DAOH without censoring zero allows for differences between procedures and DHBs to be identified. Risk-adjusted national mean DAOH90 Scores were 64.0 days, 79.0 days and 82.0 days at the 0.1 decile and 75.0 days, 82.0 days and 84.0 days at the 0.2 decile for AL, THR and LSCS, respectively, matching to their expected risk profiles. Differences between procedures and DHBs were most marked at lower deciles of the DAOH90 distribution, and outlier DHBs were detectable. Corresponding 90-day mortality rates were 5.45%, 0.78% and 0.01%. CONCLUSION: In New Zealand after direct risk adjustment, differences in DAOH90 between three types of surgical procedure reflected their respective risk levels and associated mortality rates. Outlier DHBs were identified for each procedure. Thus, our approach to analysing DAOH90 appears to have considerable face validity and potential utility for contributing to the measurement of perioperative outcomes in an audit or quality improvement setting.

Temporal validation of a multivariable surgical mortality prediction model (NZRisk): a New Zealand national cohort study.

OBJECTIVES: Clinical risk calculators (CRCs), such as NZRisk, are used daily by clinicians to guide clinical decisions and explain individual risk to patients. The utility and robustness of these tools depends on the methods used to create the underlying mathematical model, as well as the stability of that model in relation to changing clinical practice and patient populations over time. The later should be checked by temporal validation using external data. Few if any of the clinical prediction models in current clinical use have published temporal validation. Here, we use a large external dataset to temporally validate NZRisk; a perioperative risk prediction model used in the New Zealand population. METHODS: A sample of 1 976 362 adult non-cardiac surgical procedures collected over 15 years from the New Zealand Ministry of Health National Minimum Dataset, was used to temporally validate NZRisk. We divided the dataset into 15 single year cohorts and compared 13 of these to our NZRisk model (2 years used for the model building were excluded). We compared the area under the curve (AUC) value, calibration slope and intercept for each single year cohort, to the same values produced by the data used to create NZRisk, by fitting a random effects meta-regression with each year cohort acting as a separate study point. In addition, we used two-sided t-tests to compare each measure across the cohorts. RESULTS: The AUC values for the 30-day NZRisk model applied to our single year cohorts ranged from 0.918 to 0.940 (NZRisk AUC was 0.921). There were eight statistically different AUC values for the following years 2007-2009, 2016 and 2018-2021. The intercept values ranged from -0.004 to 0.007 and 7 years had statistically significant different intercepts during leave-one-out t-tests; 2007-2010, 2012, 2018 and 2021. The slope values ranged from 0.72 to 1.12 and 7 years had statistically significant different slopes during leave-one-out t-tests; 2010, 2011, 2017, 2018 and 2019-2021. The random effects meta-regression upheld our results related to AUC (0.54 (95% CI 0.40 to 0.99), I2 67.57 (95% CI 40.67 to 88.50), Cochran's Q<0.001) and slope (τ 0.14 (95% CI 0.01 to 0.23), I2 98.61 (95% CI 97.31 to 99.50), Cochran's Q<0.001) between year difference. CONCLUSION: The NZRisk model shows differences in AUC and slope but not intercept values over time. The biggest differences were in the calibration slope. The models maintained excellent discrimination over time as shown by the AUC values. These findings suggest we update our model in the next 5 years. To our knowledge, this is the first temporal validation of a CRC in current use.

Processed electroencephalography-guided general anaesthesia to reduce postoperative delirium: a systematic review and meta-analysis.

BACKGROUND: Postoperative delirium (POD) is the most common serious postoperative complication in older adults. It has uncertain aetiology, limited preventative strategies, and poor long-term outcomes. This updated systematic review and meta-analysis aimed to estimate the effect of processed electroencephalography (pEEG)-guided general anaesthesia during surgery on POD incidence. METHODS: We performed a systematic review and meta-analysis by searching OVID MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases. Studies of adult patients having general anaesthesia for any surgery where pEEG was used and POD was an outcome measure were included. Full-text reports of RCTs published from database inception until August 28, 2021, were included. Trials were excluded if sedation rather than general anaesthesia was administered, or the setting was intensive care. The primary outcome was POD assessed by validated tools. The study was prospectively registered with PROSPERO. RESULTS: Nine studies, which included 4648 eligible subjects, were identified. The incidence of POD in the pEEG-guided general anaesthesia or lighter pEEG target group was 19.0% (440/2310) compared with 23.3% (545/2338) in the usual care or deeper pEEG target group (pooled odds ratio=0.78; 95% confidence interval, 0.60-1.00; P=0.054). Significant heterogeneity was detected (I2=53%). CONCLUSIONS: Our primary analysis demonstrated a highly sensitive result with a pooled analysis of trials in which the intervention group adhered to manufacturer's recommended guidelines, showing reduced incidence of POD with pEEG guidance. High clinical heterogeneity limits inferences from this and any future meta-analyses. CLINICAL TRIAL REGISTRATION: CRD42020199404 (PROSPERO).

Understanding disparities in post-operative mortality for Indigenous patients.

There is an urgent need for high-quality evidence regarding post-operative mortality among Indigenous peoples. Our group recently published a national audit of 4,000,000 procedures conducted between 2005-2017, which identified considerable disparities in post-operative mortality between Indigenous Maori and non-Indigenous New Zealanders. Understanding the primary drivers of these disparities-for Maori, but likely also other Indigenous populations worldwide-requires us to consider the multiple levels at which these drivers might arise. To that end, in this paper we breakdown these drivers in detail, conceptualising these drivers as operating in layers with each factor leading to the next. These layers include structural factors, care system factors, care process factors, care team factors and patient factors. Each of these factors are presented within a framework that can be used to begin to understand them - with a view to rousing action and inspiring intervention to address inequities in post-operative outcomes experienced by Indigenous peoples.

End the confusion: general anaesthesia improves patient outcomes in endovascular thrombectomy.

Expert physiological and pharmacological care by anaesthetists is required in all stroke endovascular thrombectomy cases. RCTs show clinical benefits in recanalisation rates and functional recovery after endovascular thrombectomy with general anaesthesia compared with sedation. Many stroke centres will require wholesale reorganisation of stroke pathways to ensure anaesthesia services are available for all cases. Anaesthetists have an integral role in improving clinical outcomes in large vessel occlusion stroke.

Active conductive head cooling of normal and infarcted brain: A magnetic resonance spectroscopy imaging study.

Active conductive head cooling is a simple and non-invasive intervention that may slow infarct growth in ischemic stroke. We investigated the effect of active conductive head cooling on brain temperature using whole brain echo-planar spectroscopic imaging. A cooling cap (WElkins Temperature Regulation System, 2nd Gen) was used to administer cooling for 80 minutes to healthy volunteers and chronic stroke patients. Whole brain echo-planar spectroscopic imaging scans were obtained before and after cooling. Brain temperature was estimated using the Metabolite Imaging and Data Analysis System software package, which allows voxel-level temperature calculations using the chemical shift difference between metabolite (N-acetylaspartate, creatine, choline) and water resonances. Eleven participants (six healthy volunteers, five post-stroke) underwent 80 ± 5 minutes of cooling. The average temperature of the coolant was 1.3 ± 0.5°C below zero. Significant reductions in brain temperature (ΔT = -0.9 ± 0.7°C, P = 0.002), and to a lesser extent, rectal temperature (ΔT = -0.3 ± 0.1°C, P = 0.03) were observed. Exploratory analysis showed that the occipital lobes had the greatest reduction in temperature (ΔT = -1.5 ± 1.2°C, P = 0.002). Regions of infarction had similar temperature reductions to the contralateral normal brain. Future research could investigate the feasibility of head cooling as a potential neuroprotective strategy in patients being considered for acute stroke therapies.

Bone grafting for scaphoid nonunion surgery : a systematic review and meta-analysis.

AIMS: The purpose of this systematic review was to determine the rates of union for vascularized versus non-vascularized grafting techniques in the operative management of scaphoid nonunion. Secondary aims were to determine the effect of the fixation techniques used, the source of grafting, as well as the influence of fracture location (proximal pole) and avascular necrosis (AVN). METHODS: A search of PubMed, MEDLINE, and Embase was performed in June 2021 using the Preferred Reporting Items for Systematic Review and Meta-Analyses statement and registered using the PROSPERO International prospective register of systematic reviews. The primary outcome was union rate. RESULTS: There were 78 studies that met the inclusion criteria with a total of 7,671 patients (87.8% male, 12.2% female). The mean age was 27.9 years (SD 3.8) and the mean follow-up was 30.9 months (SD 25.9). The mean union rate was 88.7% (95% confidence interval (CI) 85.0 to 92.5) for non-vascularized grafts versus 87.5% (95% CI 82.8 to 92.2) for vascularized grafts (p = 0.685). Pooled analysis of trial data alone found a mean union rate of 82.4% (95% CI 66.9% to 97.9%) for non-vascularized grafts and 89.4% (95% CI 84.1% to 94.7%) for vascularized grafts (p = 0.780). No significant difference was observed in union rates between any of the fixation techniques used in the studies (p = 0.502). Distal radius and iliac crest graft source had comparable mean union rates (86.9% (95% CI 83.1 to 90.7) vs 87.6% (95% CI 82.2 to 92.9); p = 0.841). Studies that excluded patients with both proximal pole fractures and AVN (n = 14) had a mean union rate of 96.5% (95% CI 94.2 to 98.9) that was significantly greater than the mean union rate of 86.8% (95% CI 83.2 to 90.4) observed in the remaining studies (p < 0.001). CONCLUSION: Current evidence suggests vascularized bone grafting does not yield significantly superior results to non-vascularized grafting in scaphoid nonunion management. However, potential selection bias lessens the certainty of these findings. The fixation type or source of the graft used was not found to influence union rates either. Sufficiently designed and powered prospective randomized controlled trials in this area are needed. Cite this article: Bone Joint J 2022;104-B(5):549-558.

Protocol for the MAnagement of Systolic blood pressure during Thrombectomy by Endovascular Route for acute ischemic STROKE randomized clinical trial: The MASTERSTROKE trial.

REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12619001274167p. RATIONALE: Cerebral blood flow is blood pressure-dependent when cerebral autoregulation is impaired. Cerebral ischemia and anesthetic drugs impair cerebral autoregulation. In ischemic stroke patients treated with endovascular thrombectomy, induced hypertension is a plausible intervention to increase blood flow in the ischemic penumbra until reperfusion is achieved. This could potentially reduce final infarct size and improve functional recovery. AIM: To test if patients with large vessel occlusion stroke treated with endovascular thrombectomy will benefit from induced hypertension. DESIGN: Prospective, randomized, parallel group, open label, multicenter clinical trial with blinded assessment of outcomes. PROCEDURES: Patients with anterior circulation stroke treated with endovascular thrombectomy with general anesthesia within 6 h of symptom onset, and patients with 'wake up' stroke or presenting within 6 to 24 h with potentially salvageable tissue on computed tomography perfusion scanning, are included. Participants are randomized to a systolic blood pressure target of 140 mmHg or 170 mmHg from procedure initiation until recanalization. Methods to maintain the blood pressure are at the discretion of the procedural anesthesiologist. STUDY OUTCOMES: The primary efficacy outcome is improvement in disability measured by modified Rankin Scale score at 90 days. The primary safety outcome is all-cause mortality at 90 days. ANALYSIS: The Mann-Whitney U test will be used to test the ordinal shift in the seven-category modified Rankin Scale score. All-cause mortality will be estimated using the Kaplan-Meier method and compared using a log-rank test.

Disparities in post-operative mortality between Maori and non-Indigenous ethnic groups in New Zealand.

AIM: To describe disparities in post-operative mortality experienced by Indigenous Maori compared to non-Indigenous New Zealanders. METHODS: We completed a national study of all those undergoing a surgical procedure between 2005 and 2017 in New Zealand. We examined 30-day and 90-day post-operative mortality for all surgical specialties and by common procedures. We compared age-standardised rates between ethnic groups (Maori, Pacific, Asian, European, MELAA/Other) and calculated hazard ratios (HRs) using Cox proportional hazards regression modelling adjusted for age, sex, deprivation, rurality, comorbidity, ASA score, anaesthetic type, procedure risk and procedure specialty. RESULTS: From nearly 3.9 million surgical procedures (876,976 acute, 2,990,726 elective/waiting list), we observed ethnic disparities in post-operative mortality across procedures, with the largest disparities occurring between Maori and Europeans. Maori had higher rates of 30- and 90-day post-operative mortality across most broad procedure categories, with the disparity between Maori and Europeans strongest for elective/waiting list procedures (eg, elective/waiting list musculoskeletal procedures, 30-day mortality: adj. HR 1.93, 95% CI 1.56-2.39). CONCLUSIONS: The disparities we observed are likely driven by a combination of healthcare system, process and clinical team factors, and we have presented the key mechanisms within these factors.

Revisiting Ophidiomycosis (Snake Fungal Disease) After a Decade of Targeted Research.

Emerging infectious diseases (EIDs) are typically characterized by novelty (recent detection) and by increasing incidence, distribution, and/or pathogenicity. Ophidiomycosis, also called snake fungal disease, is caused by the fungus Ophidiomyces ophidiicola (formerly "ophiodiicola"). Ophidiomycosis has been characterized as an EID and as a potential threat to populations of Nearctic snakes, sparking over a decade of targeted research. However, the severity of this threat is unclear. We reviewed the available literature to quantify incidence and effects of ophidiomycosis in Nearctic snakes, and to evaluate whether the evidence supports the ongoing characterization of ophidiomycosis as an EID. Data from Canada remain scarce, so we supplemented the literature review with surveys for O. ophidiicola in the Canadian Great Lakes region. Peer-reviewed reports of clinical signs consistent with ophidiomycosis in free-ranging, Nearctic snakes date back to at least 1998, and retrospective molecular testing of samples extend the earliest confirmed record to 1986. Diagnostic criteria varied among publications (n = 33), confounding quantitative comparisons. Ophidiomycosis was diagnosed or suspected in 36/121 captive snakes and was fatal in over half of cases (66.7%). This result may implicate captivity-related stress as a risk factor for mortality from ophidiomycosis, but could also reflect reporting bias (i.e., infections are more likely to be detected in captive snakes, and severe cases are more likely to be reported). In contrast, ophidiomycosis was diagnosed or suspected in 441/2,384 free-ranging snakes, with mortality observed in 43 (9.8 %). Ophidiomycosis was only speculatively linked to population declines, and we found no evidence that the prevalence of the pathogen or disease increased over the past decade of targeted research. Supplemental surveys and molecular (qPCR) testing in Ontario, Canada detected O. ophidiicola on 76 of 657 free-ranging snakes sampled across ~136,000 km2. The pathogen was detected at most sites despite limited and haphazard sampling. No large-scale mortality was observed. Current evidence supports previous suggestions that the pathogen is a widespread, previously unrecognized endemic, rather than a novel pathogen. Ophidiomycosis may not pose an imminent threat to Nearctic snakes, but further research should investigate potential sublethal effects of ophidiomycosis such as altered reproductive success that could impact population growth, and explore whether shifting environmental conditions may alter host susceptibility.

"We can't just have a casual conversation": An institutional ethnography-informed study of work in labour and birth.

Labour and delivery units often become contested workplaces with tensions between obstetrics, nursing, and midwifery practices. These tensions can impede communication and raise concerns about provider wellness and patient safety. Remedying such tensions requires inquiry into the drivers of recurrent problems in interprofessional practice. We engaged in change-oriented inquiry informed by institutional ethnography (IE) within an academic hospital in Toronto, Canada (2017-2019). Clinicians identified critical incident analysis reports used to document recurrent issues for transfers of care (TOC) and consultations between professionals. We then mapped the everyday/everynight work of midwives, nurses, and obstetricians by observing (75 h) and interviewing them (n = 15). We also traced work processes to local (forms and hospital policies) and external (national policies and evidence-based guidelines) texts. Our IE-informed analysis made visible the otherwise hidden links between the everyday work of practitioners and its social organization. Three intrapartum work processes involving midwives consulting with obstetricians were identified: induction of labour with TOC back to midwife once labour was "active", consultation without TOC, and TOC for various indications. Three points of disjuncture complicated these processes: (i) a local "3 consult rule", linked to medico-legal governance and remuneration structures; (ii) subjective interpretations of the "4-cm dilation rule", a policy meant to standardize practice; and (iii) regulations delaying the timing of consultations. The Electronic Fetal Monitoring system served as a powerful text, materializing issues of professional scope and autonomy for midwives, and medicolegal accountability for obstetricians. Our study extends extant evidence that medicine-driven governance of midwifery practices can perpetuate interprofessional challenges. While practitioners spoke of the three disjunctures as 'laws', most also viewed them as ostensibly modifiable. Interprofessional tensions may be addressed by considering how social organization, materialized in texts detailing medico-legal liability and remuneration, can constrain possible practices through regulatory protocols, local ruling policies, and cultural expectations (e.g., documentation practices).