Description of a Multi-faceted COVID-19 Pandemic Physician Workforce Plan at a Multi-site Academic Health System.

BACKGROUND: The evolving COVID-19 pandemic has and continues to present a threat to health system capacity. Rapidly expanding an existing acute care physician workforce is critical to pandemic response planning in large urban academic health systems. INTERVENTION: The Medical Emergency-Pandemic Operations Command (MEOC)-a multi-specialty team of physicians, operational leaders, and support staff within an academic Department of Medicine in Calgary, Canada-partnered with its provincial health system to rapidly develop a comprehensive, scalable pandemic physician workforce plan for non-ventilated inpatients with COVID-19 across multiple hospitals. The MEOC Pandemic Plan comprised seven components, each with unique structure and processes. METHODS: In this manuscript, we describe MEOC's Pandemic Plan that was designed and implemented from March to May 2020 and re-escalated in October 2020. We report on the plan's structure and process, early implementation outcomes, and unforeseen challenges. Data sources included MEOC documents, health system, public health, and physician engagement implementation data. KEY RESULTS: From March 5 to October 26, 2020, 427 patients were admitted to COVID-19 units in Calgary hospitals. In the initial implementation period (March-May 2020), MEOC communications reached over 2500 physicians, leading to 1446 physicians volunteering to provide care on COVID-19 units. Of these, 234 physicians signed up for hospital shifts, and 227 physicians received in-person personal protective equipment simulation training. Ninety-three physicians were deployed on COVID-19 units at four large acute care hospitals. The resurgence of cases in September 2020 has prompted re-escalation including re-activation of COVID-19 units. CONCLUSIONS: MEOC leveraged an academic health system partnership to rapidly design, implement, and refine a comprehensive, scalable COVID-19 acute care physician workforce plan whose components are readily applicable across jurisdictions or healthcare crises. This description may guide other institutions responding to COVID-19 and future health emergencies.

Association of NT-proBNP and BNP With Future Clinical Outcomes in Patients With ESKD: A Systematic Review and Meta-analysis.

RATIONALE & OBJECTIVE: Use of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) for cardiovascular (CV) risk assessment in patients with end-stage kidney disease (ESKD) remains unclear. We examined the associations between different threshold elevations of these peptide levels and clinical outcomes in patients with ESKD. STUDY DESIGN: Systematic review and meta-analysis. SETTING & STUDY POPULATIONS: We searched MEDLINE and EMBASE (through September 2019) for observational studies of adults with ESKD (estimated glomerular filtration rate≤15mL/min/1.73m2 or receiving maintenance dialysis). SELECTION CRITERIA FOR STUDIES: Studies that reported NT-proBNP or BNP levels and future CV events, CV mortality, or all-cause mortality. DATA EXTRACTION: Cohort characteristics and measures of risk associated with study-specified peptide thresholds. ANALYTICAL APPROACH: Hazard ratios (HRs) for clinical outcomes associated with different NT-proBNP and BNP ranges were categorized into common thresholds and pooled using random-effects meta-analysis. RESULTS: We identified 61 studies for inclusion in our review (19,688 people). 49 provided sufficient detail for inclusion in meta-analysis. Pooled unadjusted HRs for CV mortality were progressively greater for greater thresholds of NT-proBNP, from 1.45 (95% CI, 0.91-2.32) for levels>2,000pg/mL to 5.95 (95% CI, 4.23-8.37) for levels>15,000pg/mL. Risk for all-cause mortality was significantly higher at all NT-proBNP thresholds ranging from> 1,000 to> 20,000pg/mL (HR range, 1.53-4.00). BNP levels>550pg/mL were associated with increased risk for CV mortality (HR, 2.54; 95% CI, 1.49-4.33), while the risks for all-cause mortality were 2.04 (95% CI, 0.82-5.12) at BNP levels>100pg/mL and 2.97 (95% CI, 2.21-3.98) at BNP levels>550pg/mL. Adjusted analyses demonstrated similarly greater risks for CV and all-cause mortality with greater NT-proBNP concentrations. LIMITATIONS: Incomplete outcome reporting and risk for outcome reporting bias. Estimation of risk for CV events for specific thresholds of both peptides were limited by poor precision. CONCLUSIONS: ESKD-specific NT-proBNP and BNP level thresholds of elevation are associated with increased risk for CV and all-cause mortality. This information may help guide interpretation of NT-proBNP and BNP levels in patients with ESKD.

Arsenic Triglutathione [As(GS)3] Transport by Multidrug Resistance Protein 1 (MRP1/ABCC1) Is Selectively Modified by Phosphorylation of Tyr920/Ser921 and Glycosylation of Asn19/Asn23.

The ATP-binding cassette (ABC) transporter multidrug resistance protein 1 (MRP1/ABCC1) is responsible for the cellular export of a chemically diverse array of xenobiotics and endogenous compounds. Arsenic, a human carcinogen, is a high-affinity MRP1 substrate as arsenic triglutathione [As(GS)3]. In this study, marked differences in As(GS)3 transport kinetics were observed between MRP1-enriched membrane vesicles prepared from human embryonic kidney 293 (HEK) (Km 3.8 µM and Vmax 307 pmol/mg per minute) and HeLa (Km 0.32 µM and Vmax 42 pmol/mg per minute) cells. Mutant MRP1 lacking N-linked glycosylation [Asn19/23/1006Gln; sugar-free (SF)-MRP1] expressed in either HEK293 or HeLa cells had low Km and Vmax values for As(GS)3, similar to HeLa wild-type (WT) MRP1. When prepared in the presence of phosphatase inhibitors, both WT- and SF-MRP1-enriched membrane vesicles had a high Km value for As(GS)3 (3-6 µM), regardless of the cell line. Kinetic parameters of As(GS)3 for HEK-Asn19/23Gln-MRP1 were similar to those of HeLa/HEK-SF-MRP1 and HeLa-WT-MRP1, whereas those of single glycosylation mutants were like those of HEK-WT-MRP1. Mutation of 19 potential MRP1 phosphorylation sites revealed that HEK-Tyr920Phe/Ser921Ala-MRP1 transported As(GS)3 like HeLa-WT-MRP1, whereas individual HEK-Tyr920Phe- and -Ser921Ala-MRP1 mutants were similar to HEK-WT-MRP1. Together, these results suggest that Asn19/Asn23 glycosylation and Tyr920/Ser921 phosphorylation are responsible for altering the kinetics of MRP1-mediated As(GS)3 transport. The kinetics of As(GS)3 transport by HEK-Asn19/23Gln/Tyr920Glu/Ser921Glu were similar to HEK-WT-MRP1, indicating that the phosphorylation-mimicking substitutions abrogated the influence of Asn19/23Gln glycosylation. Overall, these data suggest that cross-talk between MRP1 glycosylation and phosphorylation occurs and that phosphorylation of Tyr920 and Ser921 can switch MRP1 to a lower-affinity, higher-capacity As(GS)3 transporter, allowing arsenic detoxification over a broad concentration range.

Re-Purposing the Ordering of Routine Laboratory Tests in Hospitalized Medical Patients (RePORT): protocol for a multicenter stepped-wedge cluster randomised trial to evaluate the impact of a multicomponent intervention bundle to reduce laboratory test over-utilization.

BACKGROUND: Laboratory test overuse in hospitals is a form of healthcare waste that also harms patients. Developing and evaluating interventions to reduce this form of healthcare waste is critical. We detail the protocol for our study which aims to implement and evaluate the impact of an evidence-based, multicomponent intervention bundle on repetitive use of routine laboratory testing in hospitalized medical patients across adult hospitals in the province of British Columbia, Canada. METHODS: We have designed a stepped-wedge cluster randomized trial to assess the impact of a multicomponent intervention bundle across 16 hospitals in the province of British Columbia in Canada. We will use the Knowledge to Action cycle to guide implementation and the RE-AIM framework to guide evaluation of the intervention bundle. The primary outcome will be the number of routine laboratory tests ordered per patient-day in the intervention versus control periods. Secondary outcome measures will assess implementation fidelity, number of all common laboratory tests used, impact on healthcare costs, and safety outcomes. The study will include patients admitted to adult medical wards (internal medicine or family medicine) and healthcare providers working in these wards within the participating hospitals. After a baseline period of 24 weeks, we will conduct a 16-week pilot at one hospital site. A new cluster (containing approximately 2-3 hospitals) will receive the intervention every 12 weeks. We will evaluate the sustainability of implementation at 24 weeks post implementation of the final cluster. Using intention to treat, we will use generalized linear mixed models for analysis to evaluate the impact of the intervention on outcomes. DISCUSSION: The study builds upon a multicomponent intervention bundle that has previously demonstrated effectiveness. The elements of the intervention bundle are easily adaptable to other settings, facilitating future adoption in wider contexts. The study outputs are expected to have a positive impact as they will reduce usage of repetitive laboratory tests and provide empirically supported measures and tools for accomplishing this work. TRIAL REGISTRATION: This study was prospectively registered on April 8, 2024, via ClinicalTrials.gov Protocols Registration and Results System (NCT06359587). https://classic. CLINICALTRIALS: gov/ct2/show/NCT06359587?term=NCT06359587&recrs=ab&draw=2&rank=1.

Rates of 30-day revisit to the emergency department among older adults living with dementia: a systematic review and meta-analysis.

OBJECTIVE: Older adults visit emergency departments (EDs) at higher rates than their younger counterparts. However, less is known about the rate at which older adults living with dementia visit and revisit EDs. We conducted a systematic review and meta-analysis to quantify the revisit rate to the ED among older adults living with a dementia diagnosis. METHODS: We searched MEDLINE, Embase, and CINAHL, as well as gray literature, to identify observational studies reporting on older adults living with dementia that revisited an ED within 30 days of a prior ED visit. We calculated pooled rates of 30-day revisit as percentages using random effects models, and conducted stratified analyses by study data source, study population, and study period. We assessed between-studies heterogeneity using the I2 statistic and considered [Formula: see text] > 50% to indicate substantial heterogeneity. All analyses were performed in R software. RESULTS: We identified six articles for inclusion. Percentages of 30-day ED revisit among older adults living with dementia ranged widely from 16.1% to 58.0%. The overall revisit rate of 28.6% showed significant heterogeneity. Between-studies heterogeneity across all stratified analyses was also high. By data source, 30-day revisit percentages were 52.3% (public hospitals) and 20.0% (administrative databases); by study population, revisit percentages were 33.5% (dementia as main population) and 19.8% (dementia as a subgroup). By study period, revisit percentages were 41.2% (5 years or greater) and 18.9% (5 years or less). CONCLUSION: Existing literature on ED revisits among older adults living with dementia highlights the medical complexities and challenges surrounding discharge and follow-up care that may cause these patients to seek ED care at an increased rate. ED personnel may play an important role in connecting patients and caregivers to more appropriate medical and social resources in order to deliver an efficient and more rounded approach to care.

RéSUMé: OBJECTIFS: Les personnes âgées se rendent aux services d'urgence (SU) à des taux plus élevés que leurs homologues plus jeunes. Cependant, on sait moins à quelle fréquence les personnes âgées vivant avec une démence se rendent et retournent aux SU. Nous avons mené une revue systématique et une méta-analyse pour quantifier le taux de retour aux SU chez les personnes âgées vivant avec un diagnostic de démence. MéTHODES: Nous avons effectué une recherche dans MEDLINE, Embase et CINAHL, ainsi que dans la littérature grise, pour identifier les études observationnelles rapportant sur les personnes âgées vivant avec une démence qui sont retournées aux SU dans les 30 jours suivant une visite antérieure aux SU. Nous avons calculé les taux de retour à 30 jours en pourcentage en utilisant des modèles à effets aléatoires, et nous avons effectué des analyses stratifiées selon la source des données de l'étude, la population de l'étude et la période de l'étude. Nous avons évalué l'hétérogénéité entre les études à l'aide de la statistique I2 et avons considéré I

Retrospective audit of a convenience cohort of individuals on HIV pre-exposure prophylaxis in Alberta, Canada.

BACKGROUND: We undertook an audit of a province-wide HIV pre-exposure prophylaxis (PrEP) program in Alberta (Canada). METHODS: A retrospective record review of individuals accessing PrEP in Alberta included demographics, PrEP indication(s), and reported non-prescription drug and alcohol use from March 2016 to June 2019. Hepatitis A, B, C, HIV and syphilis serology, serum creatinine, and nucleic acid amplification tests testing for chlamydia and gonorrhea were collected. Descriptive statistics, incidence, and prevalence were calculated. RESULTS: A total of 511 participants were seen at STI, sexual, and reproductive health clinics and private family practitioner (FP) offices; 98.4% (503) were men, median age was 34 years (IQR 28-43 years), and 89.8% (459) were gay or bisexual men who have sex with men. Non-prescription drug use was reported by 39.3% (201) and alcohol use by 55.4% (283). 94.3% (482) reported condomless anal sex in the past 6 months. Testing rates were high (>95%) for all tests except for chlamydia and gonorrhea at the first follow-up visit 89.6%; (3-4 months). There was one HIV seroconversion. The incidence of new bacterial STIs was high: chlamydia 17 cases per 100 person-years (95% CI 13.5% to 21.4%), gonorrhea 11.14 cases per 100 person-years (95% CI 8.3% to 15.0%), and syphilis 1.94 cases per 100 person-years (95% CI 0.73% to 5.12%). CONCLUSIONS: Following implementation of a provincial program for PrEP in Alberta, PrEP initiation and continuation was feasible in a range of settings and by both specialists and FPs.

HISTORIQUE: Les chercheurs ont entrepris une vérification du programme provincial de prophylaxie pré-exposition (PrEP) du VIH en Alberta, au Canada. MÉTHODOLOGIE: Les chercheurs ont procédé à une analyse rétrospective des dossiers des personnes qui ont eu accès à la PrEP en Alberta, y compris les données démographiques, les indications d'administrer une PrEP et la consommation déclarée de médicaments sans ordonnance et d'alcool entre mars 2016 et juin 2019. Ils ont recueilli la sérologie de l'hépatite A, B et C, du VIH et de la syphilis, la créatinine sérique et les tests d'amplification des acides nucléiques de la Chlamydia et de la gonorrhée. Ils ont également calculé les statistiques descriptives, l'incidence et la prévalence de ces maladies. RÉSULTATS: Au total, 511 participants ont été vus dans des cliniques d'ITS, de santé sexuelle et de santé reproductive ainsi qu'au cabinet de médecins de famille privés, soit 98,4 % d'hommes (503), d'un âge médian de 34 ans (ÉIQ : 28 à 43 ans) et 89,8 % (459) d'hommes gay ou bisexuels qui avaient des relations sexuelles avec d'autres hommes. Ainsi, 39,3 % (201) ont déclaré consommer des médicaments sans ordonnance et 55,4 % (283), de l'alcool. De plus, 94,3 % (482) ont indiqué avoir eu des relations sexuelles anales sans préservatif au cours des six mois précédents. Les taux de dépistage étaient élevés (>95 %) à l'égard de tous les tests au premier rendez-vous de suivi (au bout de trois à quatre mois), sauf ceux de la Chlamydia et de la gonorrhée, qui s'élevaient à 89,6 %. Un cas de séroconversion du VIH a été constaté. L'incidence de nouvelles ITS bactérienne était élevée : 17 cas de Chlamydia par 100 années-personnes (IC à 95 %, 13,5 % à 21,4 %), 11,14 cas de gonorrhée par 100 années-personnes (IC à 95 %, 8,3 % à 15,0 %) et 1,94 cas de syphilis par 100 années-personnes (IC à 95 %, 0,73 % à 5,12 %). CONCLUSIONS: Après la mise en œuvre d'un programme provincial de PrEP en Alberta, il a été établi qu'il était possible d'entreprendre et de poursuivre la PrEP dans divers milieux, à l'instigation de spécialistes tout autant que de médecins de famille.

Monomethylarsenic diglutathione transport by the human multidrug resistance protein 1 (MRP1/ABCC1).

The ATP-binding cassette (ABC) transporter protein multidrug resistance protein 1 (MRP1; ABCC1) plays an important role in the cellular efflux of the high-priority environmental carcinogen arsenic as a triglutathione conjugate [As(GS)(3)]. Most mammalian cells can methylate arsenic to monomethylarsonous acid (MMA(III)), monomethylarsonic acid (MMA(V)), dimethylarsinous acid (DMA(III)), and dimethylarsinic acid (DMA(V)). The trivalent forms MMA(III) and DMA(III) are more reactive and toxic than their inorganic precursors, arsenite (As(III)) and arsenate (As(V)). The ability of MRP1 to transport methylated arsenicals is unknown and was the focus of the current study. HeLa cells expressing MRP1 (HeLa-MRP1) were found to confer a 2.6-fold higher level of resistance to MMA(III) than empty vector control (HeLa-vector) cells, and this resistance was dependent on GSH. In contrast, MRP1 did not confer resistance to DMA(III), MMA(V), or DMA(V). HeLa-MRP1 cells accumulated 4.5-fold less MMA(III) than HeLa-vector cells. Experiments using MRP1-enriched membrane vesicles showed that transport of MMA(III) was GSH-dependent but not supported by the nonreducing GSH analog, ophthalmic acid, suggesting that MMA(III)(GS)(2) was the transported form. MMA(III)(GS)(2) was a high-affinity, high-capacity substrate for MRP1 with apparent K(m) and V(max) values of 11 µM and 11 nmol mg(-1)min(-1), respectively. MMA(III)(GS)(2) transport was osmotically sensitive and inhibited by several MRP1 substrates, including 17ß-estradiol 17-(ß-D-glucuronide) (E(2)17ßG). MMA(III)(GS)(2) competitively inhibited the transport of E(2)17ßG with a K(i) value of 16 µM, indicating that these two substrates have overlapping binding sites. These results suggest that MRP1 is an important cellular protective pathway for the highly toxic MMA(III) and have implications for environmental and clinical exposure to arsenic.

Comparative Analysis of Molecular and Serologic Testing for Primary Syphilis: A Population-Based Cohort Study.

Rising rates of syphilis (T. pallidum; Tp) requires rapid diagnosis and treatment to manage the growing epidemic. Syphilis serology is imperfect and requires interpretation of multiple tests while molecular diagnostics allows for potential yes-no identification of highly infective, primary anogenital lesions. Accuracy of this testing modality has thus far been limited to small, highly selective studies. Therefore, we retrospectively assessed a large, adult population of patients with anogenital lesions seen at Sexually Transmitted Infection (STI) clinics in Alberta, Canada who were screened for syphilis and herpes simplex (HSV) 1/2 using PCR to evaluate Tp-PCR versus serology to diagnose primary syphilis. 114 (3.1%) of the 3,600 adult patients had at least one Tp-PCR+ anogenital lesion with 99 (2.8%) patients having newly positive syphilis serology (new INNO-LIA positive or 4-fold RPR increase). Tp-PCR had a sensitivity of 49.3% (95% CI 42.6-56.1) and specificity of 99.9% (99.7-100.0). Positive predictive values and negative predictive values in the study population or when corrected for provincial prevalence were 97.4% (92.5-99.5) or 0.4% (0.4-1.2) and 96.7% (96.1-97.3) or 100.0% (100.0-100.0), respectively. Positive and negative likelihood ratios were estimated at 555 (178-1733) and 0.5 (0.4-0.6), respectively. Review of all Tp-PCR performed with or without exclusion of HSV-positive lesions resulted in no significant change in Tp-PCR characteristics. Interestingly, 12 of the Tp-PCR+ samples had negative serology at time of lesion sampling but became positive within our 28-day testing window. Overall, this study further supports the use of Tp-PCR as an accurate assay to rapidly identify, treat, and prevent the spread of primary syphilis.