Automated transient grating spectroscopy mapping and signal control for large samples.

We present developments for the mapping of large areas using transient grating spectroscopy (TGS) that allow for smoother, larger, autonomous measurements of material samples. The addition of a precise linear stage in the direction parallel to laser sampling coupled with signal optimizing control allows for hands free, self-correcting measurements. In addition, the simplification of the sample holding design to a form that is small enough to mount directly to the linear stage exhibits a straightforward, low-cost solution for automated TGS applications. This capability is demonstrated by taking large uninterrupted maps of gradient wafers, and the results are validated on calibrated tungsten samples and control TGS samples from gradient wafers.

The effectiveness of a multifaceted, group-facilitated audit and feedback intervention to increase tranexamic acid use during total joint arthroplasty.

PURPOSE: Intraoperative tranexamic acid (TXA) is used to reduce blood loss and the need for transfusions following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Despite evidence in literature and local practice protocols supporting TXA as a part of standard of care for joint arthroplasty, TXA administration is underutilized. We aimed to use group-facilitated audit and feedback as the foundation of a knowledge translation strategy to increase TXA use for THA and TKA procedures. METHODS: Anesthesiologists consented to receive two data reports summarizing their individual rates of TXA use and postoperative blood transfusions compared with site peers. Variables collected included patient demographics, TXA usage, and the frequency and volume of red blood cell transfusions administered in the 72-hr postoperative period. The facilitated feedback session discussed report findings and focused on factors contributing to local practice patterns and opportunities for change. RESULTS: Tranexamic acid use increased for THA procedures at the intervention site from 66.6 to 74.4% (absolute change, 7.9%; 95% confidence interval [CI], 2.4 to 13.3). Likewise, TXA use for TKA procedures increased from 62.4 to 82.3% (absolute change, 19.9%; 95% CI 15.0 to 25.0). CONCLUSIONS: Physicians and their teams were able to review their practice data on TXA utilization, reflect on differences compared with evidence-based guidelines, discuss findings with peers, and identify opportunities for improvement. The intervention increased the use of TXA for both TKA and THA and shifted the dosage to better align with evidence-based practice guidelines.

RéSUMé: OBJECTIF : L'acide tranexamique (ATX) peropératoire est utilisé pour réduire les pertes sanguines et les besoins transfusionnels après les arthroplasties totales de la hanche (ATH) et du genou (ATG). Malgré les données probantes et les protocoles de pratique locaux appuyant l'utilisation d'ATX dans le cadre de la norme de soins en cas d'arthroplastie, l'administration de cet agent est sous-utilisée. Notre objectif était d'utiliser l'audit et la rétroaction facilités par le groupe comme base d'une stratégie d'application des connaissances afin d'accroître l'utilisation de l'ATX lors des ATH et ATG. MéTHODE: Les anesthésiologistes ont consenti à recevoir deux rapports de données résumant leurs taux individuels d'utilisation d'ATX et de transfusions sanguines postopératoires par rapport à leurs pairs au sein du même établissement. Les variables recueillies comprenaient les données démographiques des patients, l'utilisation d'ATX et la fréquence et le volume des transfusions d'érythrocytes administrées au cours d'une période postopératoire de 72 heures. La séance de rétroaction facilitée a porté sur les conclusions du rapport et s'est concentrée sur les facteurs contribuant aux habitudes de pratique locales et aux possibilités de changement. RéSULTATS: L'utilisation d'acide tranexamique a augmenté pour les procédures d'ATH au site d'intervention, passant de 66,6 % à 74,4 % (variation absolue, 7,9 %; intervalle de confiance [IC] à 95 %, 2,4 à 13,3). De même, l'utilisation d'ATX pour les procédures d'ATG est passée de 62,4 % à 82,3 % (variation absolue, 19,9 %; IC 95 %, 15,0 à 25,0). CONCLUSION: Les médecins et leurs équipes ont pu passer en revue leurs données de pratique sur l'utilisation d'ATX, réfléchir aux différences par rapport aux lignes directrices fondées sur des données probantes, discuter des résultats avec leurs pairs et identifier les possibilités d'amélioration. L'intervention a augmenté l'utilisation d'ATX pour l'ATG et l'ATH et a modifié la posologie pour mieux s'aligner sur les lignes directrices de pratique fondées sur des données probantes.

Reporting of Model Performance and Statistical Methods in Studies That Use Machine Learning to Develop Clinical Prediction Models: Protocol for a Systematic Review.

BACKGROUND: With the growing excitement of the potential benefits of using machine learning and artificial intelligence in medicine, the number of published clinical prediction models that use these approaches has increased. However, there is evidence (albeit limited) that suggests that the reporting of machine learning-specific aspects in these studies is poor. Further, there are no reviews assessing the reporting quality or broadly accepted reporting guidelines for these aspects. OBJECTIVE: This paper presents the protocol for a systematic review that will assess the reporting quality of machine learning-specific aspects in studies that use machine learning to develop clinical prediction models. METHODS: We will include studies that use a supervised machine learning algorithm to develop a prediction model for use in clinical practice (ie, for diagnosis or prognosis of a condition or identification of candidates for health care interventions). We will search MEDLINE for studies published in 2019, pseudorandomly sort the records, and screen until we obtain 100 studies that meet our inclusion criteria. We will assess reporting quality with a novel checklist developed in parallel with this review, which includes content derived from existing reporting guidelines, textbooks, and consultations with experts. The checklist will cover 4 key areas where the reporting of machine learning studies is unique: modelling steps (order and data used for each step), model performance (eg, reporting the performance of each model compared), statistical methods (eg, describing the tuning approach), and presentation of models (eg, specifying the predictors that contributed to the final model). RESULTS: We completed data analysis in August 2021 and are writing the manuscript. We expect to submit the results to a peer-reviewed journal in early 2022. CONCLUSIONS: This review will contribute to more standardized and complete reporting in the field by identifying areas where reporting is poor and can be improved. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020206167; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=206167. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/30956.

Opioid prescribing among new users for non-cancer pain in the USA, Canada, UK, and Taiwan: A population-based cohort study.

BACKGROUND: The opioid epidemic in North America has been driven by an increase in the use and potency of prescription opioids, with ensuing excessive opioid-related deaths. Internationally, there are lower rates of opioid-related mortality, possibly because of differences in prescribing and health system policies. Our aim was to compare opioid prescribing rates in patients without cancer, across 5 centers in 4 countries. In addition, we evaluated differences in the type, strength, and starting dose of medication and whether these characteristics changed over time. METHODS AND FINDINGS: We conducted a retrospective multicenter cohort study of adults who are new users of opioids without prior cancer. Electronic health records and administrative health records from Boston (United States), Quebec and Alberta (Canada), United Kingdom, and Taiwan were used to identify patients between 2006 and 2015. Standard dosages in morphine milligram equivalents (MMEs) were calculated according to The Centers for Disease Control and Prevention. Age- and sex-standardized opioid prescribing rates were calculated for each jurisdiction. Of the 2,542,890 patients included, 44,690 were from Boston (US), 1,420,136 Alberta, 26,871 Quebec (Canada), 1,012,939 UK, and 38,254 Taiwan. The highest standardized opioid prescribing rates in 2014 were observed in Alberta at 66/1,000 persons compared to 52, 51, and 18/1,000 in the UK, US, and Quebec, respectively. The median MME/day (IQR) at initiation was highest in Boston at 38 (20 to 45); followed by Quebec, 27 (18 to 43); Alberta, 23 (9 to 38); UK, 12 (7 to 20); and Taiwan, 8 (4 to 11). Oxycodone was the first prescribed opioid in 65% of patients in the US cohort compared to 14% in Quebec, 4% in Alberta, 0.1% in the UK, and none in Taiwan. One of the limitations was that data were not available from all centers for the entirety of the 10-year period. CONCLUSIONS: In this study, we observed substantial differences in opioid prescribing practices for non-cancer pain between jurisdictions. The preference to start patients on higher MME/day and more potent opioids in North America may be a contributing cause to the opioid epidemic.

Emergency Department Pediatric Visits in Alberta for Cannabis After Legalization.

BACKGROUND AND OBJECTIVES: Canada legalized nonmedical cannabis possession and sale in October 2018. In the United States, state legalization has been tied to an increase in cannabis-related emergency department (ED) visits; however, little research exists on provincial changes in pediatric visits after nationwide legislation. We compared pre- and postlegalization trends in pediatric cannabis-related ED visits and presentation patterns in urban Alberta EDs. METHODS: Retrospective National Ambulatory Care Reporting System data were queried for urban Alberta cannabis-related ED visits among patients aged <18 years from October 1, 2013, to February 29, 2020. Population subgroups included children (aged 0-11 years), younger adolescents (12 to 14 years), and older adolescents (15 to 17 years). We calculated interrupted time series, incident rate ratios (IRRs), and relative risk (RR) ratios to identify trend change. IRRs identified changes against growth-adjusted Alberta population, while RRs measured presentation pattern changes against prelegalization ED visits. RESULTS: Pediatric visit volume did not change postlegalization when accounting for preexisting volume trends. Unintentional ingestions increased in children (IRR: 1.77, 95% confidence interval [CI]: 1.42 to 2.20 and RR: 1.24, 95% CI: 1.05 to 1.47, respectively) and older adolescents (IRR: 1.36, 95% CI: 1.07 to 1.71 and RR: 1.48, 95% CI: 1.21 to 1.81, respectively). Presentation patterns remained similar, although older adolescent co-ingestant use decreased (RR: 0.77, 95% CI: 0.67 to 0.88), whereas hyperemesis cases increased (RR: 1.64, 95% CI: 1.13 to 2.37). CONCLUSIONS: Cannabis legalization has increased child and older adolescent unintentional cannabis ingestions, increasing child cannabis-related ED visits. Changes highlight need for public health interventions targeting pediatric exposures.

Clearing the air: A study of cannabis-related presentations to urban Alberta emergency departments following legalization.

OBJECTIVES: Non-medical cannabis recently became legal for adults in Canada. Legalization provides opportunity to investigate the public health effects of national cannabis legalization on presentations to emergency departments (EDs). Our study aimed to explore association between cannabis-related ED presentations, poison control and telemedicine calls, and cannabis legalization. METHODS: Data were collected from the National Ambulatory Care Reporting System from October 1, 2013, to July 31, 2019, for 14 urban Alberta EDs, from Alberta poison control, and from HealthLink, a public telehealth service covering all of Alberta. Visitation data were obtained to compare pre- and post-legalization periods. An interrupted time-series analysis accounting for existing trends was completed, in addition to the incidence rate ratio (IRR) and relative risk calculation (to evaluate changes in co-diagnoses). RESULTS: Although only 3 of every 1,000 ED visits within the time period were attributed to cannabis, the number of cannabis-related ED presentations increased post-legalization by 3.1 (range -11.5 to 12.6) visits per ED per month (IRR 1.45, 95% confidence interval [CI]; 1.39, 1.51; absolute level change: 43.5 visits per month, 95% CI; 26.5, 60.4). Cannabis-related calls to poison control also increased (IRR 1.87, 95% CI; 1.55, 2.37; absolute level change: 4.0 calls per month, 95% CI; 0.1, 7.9). Lastly, we observed increases in cannabis-related hyperemesis, unintentional ingestion, and individuals leaving the ED pre-treatment. We also observed a decrease in co-ingestant use. CONCLUSION: Overall, Canadian cannabis legalization was associated with small increases in urban Alberta cannabis-related ED visits and calls to a poison control centre.

Group-facilitated audit and feedback to improve bronchiolitis care in the emergency department.

OBJECTIVE: Despite strong evidence recommending supportive care as the mainstay of management for most infants with bronchiolitis, prior studies show that patients still receive low-value care (e.g., respiratory viral testing, salbutamol, chest radiography). Our objective was to decrease low-value care by delivering individual physician reports, in addition to group-facilitated feedback sessions to pediatric emergency physicians. METHODS: Our cohort included 3,883 patients ≤ 12 months old who presented to pediatric emergency departments in Calgary, Alberta, with a diagnosis of bronchiolitis from April 1, 2013, to April 30, 2018. Using administrative data, we captured baseline characteristics and therapeutic interventions. Consenting pediatric emergency physicians received two audit and feedback reports, which included their individual data and peer comparators. A multidisciplinary group-facilitated feedback session presented data and identified barriers and enablers of reducing low-value care. The primary outcome was the proportion of patients who received any low-value intervention and was analysed using statistical process control charts. RESULTS: Seventy-eight percent of emergency physicians consented to receive their audit and feedback reports. Patient characteristics were similar in the baseline and intervention period. Following the baseline physician reports and the group feedback session, low-value care decreased from 42.6% to 27.1% (absolute difference: -15.5%; 95% CI: -19.8% to -11.2%) and 78.9% to 64.4% (absolute difference: -14.5%; 95% CI: -21.9% to -7.2%) in patients who were not admitted and admitted, respectively. Balancing measures, such as intensive care unit admission and emergency department revisit, were unchanged. CONCLUSION: The combination of audit and feedback and a group-facilitated feedback session reduced low-value care for patients with bronchiolitis.

Estimating Urine Albumin-to-Creatinine Ratio from Protein-to-Creatinine Ratio: Development of Equations using Same-Day Measurements.

BACKGROUND: Urine albumin-to-creatinine ratio (ACR) and protein-to-creatinine ratio (PCR) are used to measure urine protein. Recent guidelines endorse ACR use, and equations have been developed incorporating ACR to predict risk of kidney failure. For situations in which PCR only is available, having a method to estimate ACR from PCR as accurately as possible would be useful. METHODS: We used data from a population-based cohort of 47,714 adults in Alberta, Canada, who had simultaneous assessments of urine ACR and PCR. After log-transforming ACR and PCR, we used cubic splines and quantile regression to estimate the median ACR from a PCR, allowing for modification by specified covariates. On the basis of the cubic splines, we created models using linear splines to develop equations to estimate ACR from PCR. In a subcohort with eGFR<60 ml/min per 1.73 m2, we then used the kidney failure risk equation to compare kidney failure risk using measured ACR as well as estimated ACR that had been derived from PCR. RESULTS: We found a nonlinear association between log(ACR) and log(PCR), with the implied albumin-to-protein ratio increasing from <30% in normal to mild proteinuria to about 70% in severe proteinuria, and with wider prediction intervals at lower levels. Sex was the most important modifier of the relationship between ACR and PCR, with men generally having a higher albumin-to-protein ratio. Estimates of kidney failure risk were similar using measured ACR and ACR estimated from PCR. CONCLUSIONS: We developed equations to estimate the median ACR from a PCR, optionally including specified covariates. These equations may prove useful in certain retrospective clinical or research applications where only PCR is available.

Orthomageddon: A retrospective cohort study of weather-dependent variations in emergency department volume in a Canadian city.

INTRODUCTION: Unique weather patterns can dramatically increase the number of emergency department (ED) visits due to falls on snow or ice compared to winter averages. They can create "Orthomageddon" incidences; days when the number of orthopedic injuries dramatically exceeds average. The study objective was to identify weather-dependent differences in demographics, length-of-stay (LOS) predictors, and volume for fall-injury presenting to the ED. The authors placed emphasis on Chinook or Foehn phenomenon (rapid freeze-thaw cycles) common east of the Rocky Mountains. METHOD: Patients with extremity and hip fractures from fall on snow or ice were identified from the Calgary Zone Alberta Health Services ED database from November 1st 2013 to March 31st 2018 (n = 3894). High-volume dates were the 90th percentile of all dates by volume (n = 76). This equated to all dates with >10 fall-injuries. The authors compared post-Chinook, night-freezing, high-volume, and regular winter conditions. Meteorological data was collected from the Environment Canada weather station at the Calgary International Airport. RESULTS: The authors identified 588 post-Chinook, and 1149 night-freezing presenters. Weather was strongly predictive of ED fall-injury volume. Night-freezing events (above-freezing temperatures prior to 1800 hours the preceding day, followed by freezing temperatures prior to 0600 hours the following day) correlated with elevated fall-injury volume (OR, 6.84; 95% CI, 5.88, 7.97) as were recent Chinook events (OR, 2.19; 95% CI, 1.84, 2.62). CONCLUSION: Weather, particularly nighttime conditions, are highly predictive of winter, fall-related ED volume. This may inform future population-level alerts for dates of elevated fall risk and ED staffing patterns.

Informing Primary Care Changes in Alberta: Continuity and Potential Impacts on Acute Care.

Health systems across Canada are embarking on initiatives to enhance access to primary care services, with the intent of improving patient outcomes and mitigating escalating healthcare costs. However, it is important that such initiatives be carefully weighed with the evidence that the changes will indeed have the desired impact. In Alberta, part of the informative process involved an analysis to examine links between continuity with primary care and utilization of acute care services. The findings provide information regarding expectations for outcomes and potentially useful (and not so useful) measures for monitoring progress and performance.

A Cost Analysis and Cost-Utility Analysis of a Community Pharmacist-Led Intervention on Reducing Cardiovascular Risk: The Alberta Vascular Risk Reduction Community Pharmacy Project (RxEACH).

BACKGROUND: A randomized trial (the Alberta Vascular Risk Reduction Community Pharmacy Project) showed that a community pharmacist-led intervention was efficacious for reducing cardiovascular (CV) risk. However, the cost of this strategy is unknown. OBJECTIVES: We examined the short- and long-term cost of a pharmacist-led intervention to reduce CV risk compared to usual care. METHODS: We conducted a trial-based cost analysis from the perspective of a publicly funded healthcare system. Over 3 and 12 months of follow-up, we examined specific intervention costs (pharmacy claims), related intervention costs (laboratory tests and medications), and ongoing healthcare costs (physician claims, emergency department visits, and hospital admissions). We also used the validated CV Disease Policy Model-Canada to estimate the long-term effects. RESULTS: A total of 684 participants (mean age 62, 57% male) were included. Overall, there were no significant differences in healthcare costs at 3 or 12 months between the usual care and intervention groups (P = .127). The CV disease-related healthcare cost of managing a patient over a lifetime was estimated to be Can$45 530 (95% uncertainty interval [UI], 45 460-45 580) and Can$40 750 (95% UI, 37 780-43 620) in usual care and intervention groups, respectively, an incremental cost savings of Can$4770 per patient (95% UI, 1900-7760). The intervention dominated usual care (better outcomes and lower costs) across 3-year, 5-year, 10-year, and lifetime horizons. CONCLUSION: This economic analysis suggests that a clinical pathway-driven pharmacist-led intervention (previously shown to reduce CV risk) was associated with similar measured healthcare costs over 1 year, and lower extrapolated healthcare costs over a patient lifetime. This strategy could be broadly implemented to realize its benefits.

Healthcare Costs Attributable to Hypertension: Canadian Population-Based Cohort Study.

Accurately documenting the current and future costs of hypertension is required to fully understand the potential economic impact of currently available and future interventions to prevent and treat hypertension. The objective of this work was to calculate the healthcare costs attributable to hypertension in Canada and to project these costs to 2020. Using population-based administrative data for the province of Alberta, Canada (>3 million residents) from 2002 to 2010, we identified individuals with and without diagnosed hypertension. We calculated their total healthcare costs and estimated costs attributable to hypertension using a regression model adjusting for comorbidities and sociodemographic factors. We then extrapolated hypertension-attributable costs to the rest of Canada and projected costs to the year 2020. Twenty-one percent of adults in Alberta had diagnosed hypertension in 2010, with a projected increase to 27% by 2020. The average individual with hypertension had annual healthcare costs of $5768, of which $2341 (41%) were attributed to hypertension. In Alberta, the healthcare costs attributable to hypertension were $1.4 billion in 2010. In Canada, the hypertension-attributable costs were estimated to be $13.9 billion in 2010, rising to $20.5 billion by 2020. The increase was ascribed to demographic changes (52%), increasing prevalence (16%), and increasing per-patient costs (32%). Hypertension accounts for a significant proportion of healthcare spending (10.2% of the Canadian healthcare budget) and is projected to rise even further. Interventions to prevent and treat hypertension may play a role in limiting this cost growth.

Analyzing hospitalization data: potential limitations of Poisson regression.

BACKGROUND: Poisson regression is commonly used to analyze hospitalization data when outcomes are expressed as counts (e.g. number of days in hospital). However, data often violate the assumptions on which Poisson regression is based. More appropriate extensions of this model, while available, are rarely used. METHODS: We compared hospitalization data between 206 patients treated with hemodialysis (HD) and 107 treated with peritoneal dialysis (PD) using Poisson regression and compared results from standard Poisson regression with those obtained using three other approaches for modeling count data: negative binomial (NB) regression, zero-inflated Poisson (ZIP) regression and zero-inflated negative binomial (ZINB) regression. We examined the appropriateness of each model and compared the results obtained with each approach. RESULTS: During a mean 1.9 years of follow-up, 183 of 313 patients (58%) were never hospitalized (indicating an excess of 'zeros'). The data also displayed overdispersion (variance greater than mean), violating another assumption of the Poisson model. Using four criteria, we determined that the NB and ZINB models performed best. According to these two models, patients treated with HD experienced similar hospitalization rates as those receiving PD {NB rate ratio (RR): 1.04 [bootstrapped 95% confidence interval (CI): 0.49-2.20]; ZINB summary RR: 1.21 (bootstrapped 95% CI 0.60-2.46)}. Poisson and ZIP models fit the data poorly and had much larger point estimates than the NB and ZINB models [Poisson RR: 1.93 (bootstrapped 95% CI 0.88-4.23); ZIP summary RR: 1.84 (bootstrapped 95% CI 0.88-3.84)]. CONCLUSIONS: We found substantially different results when modeling hospitalization data, depending on the approach used. Our results argue strongly for a sound model selection process and improved reporting around statistical methods used for modeling count data.

Exploring neurotherapeutic space: how many neurological drugs exist (or could exist)?

OBJECTIVES: Since high-throughput screening of compound libraries (virtual or real) against druggable targets is increasingly being used to discover therapies for brain disorders, it is crucial to ascertain if such screening methods adequately explore 'neurotherapeutic space (i.e. the total number of molecules that are or could be neuroactive)'. We present an approach to providing an estimate of the size of neurotherapeutic space. METHODS: Molecular modelling and statistical calculations were used to determine the number of molecules, which exist or could exist, with the necessary physicochemical and structural properties to be neurologically active drugs. KEY FINDINGS: Assuming eight fundamental types of drug-receptor interactions, five different functional groups per type of interaction and five different molecular platforms for each functional group array, we calculated the total number of molecules that could be contained within a 7 Å radius sphere, used to define neuroactive chemical space. This calculation revealed that there are 6 × 10(15) molecules that could be neurological drugs. CONCLUSIONS: Clearly, when it comes to exploring neurochemical space, we are still in our infancy and conventional high-throughput screening provides only a very limited sampling of the neuroactive chemical space that is available to neurotherapeutic compounds.

A retrospective immunohistochemical study reveals atypical scrapie has existed in the United Kingdom since at least 1987.

Atypical scrapie is a relatively recent discovery, and it was unknown whether it was a new phenomenon or whether it had existed undetected in the United Kingdom national flock. Before 1998, the routine statutory diagnosis of transmissible spongiform encephalopathy (TSE) in sheep relied on the presence of TSE vacuolation in the brainstem. This method would not have been effective for the detection of atypical scrapie. Currently, immunohistochemistry (IHC) and Western blot are commonly used for the differential diagnosis of classical and atypical scrapie. The IHC pattern of PrPd deposition in atypical scrapie is very different from that in classical scrapie using the same antibody. It is thus possible that because of a lack of suitable diagnostic techniques and awareness of this form of the disease, historic cases of atypical scrapie remain undiagnosed. Immunohistochemistry was performed on selected formalin-fixed, paraffin-embedded (FFPE) blocks of ovine brain from the Veterinary Laboratories Agency archives that were submitted for various reasons, including suspect neurological disorders, between 1980 and 1989. It was found that PrPd deposits in a single case were consistent with atypical scrapie. A method was developed to obtain a PrP genotype from FFPE tissues and was applied to material from this single case, which was shown to be AHQ/AHQ. This animal was a scrapie suspect from 1987, but diagnosis was not confirmed by the available techniques at that time.