Operationalizing the principles of patient engagement through a Patient Advisory Council: Lessons and recommendations.

BACKGROUND: Inclusiveness, Support, Mutual Respect and Co-Build are the four pillars of patient engagement according to the Strategy for Patient-Oriented Research (SPOR). The aim of this manuscript is to describe the operationalization of these principles through the creation of a Patient Advisory Council (PAC) for the research study titled 'Re-Purposing the Ordering of Routine laboratory Tests (RePORT)'. METHODS: Researchers collaborated with the Alberta SPOR SUPPORT Unit (AbSPORU) Patient Engagement Team to create a diverse PAC. Recruitment was intentional and included multiple perspectives and experiences. PAC meetings were held monthly, and patient research partners received support to function as co-chairs of the PAC. Patient research partners were offered training, support and tailored modalities of compensation to actively engage with the PAC. Regular member check-ins occurred through reflexivity and a formal evaluation of PAC member engagement. RESULTS: The PAC included between 9 and 11 patient research partners, principal investigator, research study coordinator, improvement scientist, resident physician and support members from the AbSPORU team. Twelve monthly PAC meetings were held during the first phase of the project. The PAC made course-changing contributions to study design including study objectives, recruitment poster, interview guide and development of codes for thematic analysis. Patient research partners largely felt that their opinions were valued. Diversity in the PAC membership enhanced access to diverse patient participants. Furthermore, support for co-chairs and patient research partner members enabled active engagement in research. In addition, a culture of mutual respect facilitated patient partner engagement, and co-design approaches yielded rich research outputs. CONCLUSIONS: Collaboration between research teams and Patient Engagement Teams can promote effective patient engagement through a PAC. Deliberate and flexible strategies are needed to manage the PAC to create an ecology of Inclusiveness, Support, Mutual Respect, and Co-Build for meaningful patient engagement. PATIENT OR PUBLIC CONTRIBUTION: Patient research partners were involved in the decision to write this manuscript and collaborated equitably in the conception and development of this manuscript, including providing critical feedback. Patient research partners were active members of the PAC and informed the research project design, participant recruitment strategies, data collection and analysis, and will be involved in the implementation and dissemination of results. They are currently involved in the co-development of a patient engagement strategy using a Human-Centered Design process.

Patient perceptions of in-hospital laboratory blood testing: A patient-oriented and patient co-designed qualitative study.

BACKGROUND: Indiscriminate use of laboratory blood testing in hospitals contributes to patient discomfort and healthcare waste. Patient engagement in low-value healthcare can help reduce overuse. Understanding patient experience is necessary to identify opportunities to improve patient engagement with in-hospital laboratory testing. OBJECTIVES: To understand patient experience with the process of in-hospital laboratory blood testing. METHODS: We used a qualitative study design via semistructured interviews conducted online or over the phone. Participants were adult patients or family members/caregivers (≥18 years of age) with a recent (within 12 months of interview) experience of hospitalization in Alberta or British Columbia, Canada. We identified participants through convenience sampling and conducted interviews between May 2021 and June 2022. We analysed transcripts using thematic content analysis. Recruitment was continued until code saturation was reached. RESULTS: We interviewed 16 participants (13 patients, 1 family member and 2 caregivers). We identified four themes from patients' experiences of in-hospital laboratory blood testing: (i) patients need information from healthcare teams about expected blood testing processes, (ii) blood draw processes should consider patient comfort and preferences, (iii) patients want information from their healthcare teams about the rationale and frequency of blood testing and (iv) patients need information on how their testing results affect their medical care. CONCLUSION: Current laboratory testing processes in hospitals do not facilitate shared decision-making and patient engagement. Patient engagement with laboratory testing in hospitals requires an empathetic healthcare team that provides clear communication regarding testing procedures, rationale and results, while considering patient preferences and offering opportunities for involvement. PATIENT OR PUBLIC CONTRIBUTION: We interviewed 16 patients and/or family members/caregivers regarding their in-hospital laboratory blood testing experiences. Our findings show correlations between patient needs and patient recommendations to make testing processes more patient-centred. To bring a lived-experience lens to this study, we formed a Patient Advisory Council with 9-11 patient research partners. Our patient research partners informed the research design, co-developed participant recruitment strategies, co-conducted data collection and informed the data analysis. Some of our patient research partners are co-authors of this manuscript.

Association Between Health System Factors and Utilization of Routine Laboratory Tests in Clinical Teaching Units: a Cohort Analysis.

BACKGROUND: Few studies have looked at health system factors associated with laboratory test use. OBJECTIVE: To determine the association between health system factors and routine laboratory test use in medical inpatients. DESIGN: We conducted a retrospective cohort study on adult patients admitted to clinical teaching units over a 3-year period (January 2015 to December 2017) at three tertiary care hospitals in Calgary, Alberta. PARTICIPANTS: Patients were assigned to a Case Mix Group+ (CMG+) category based on their clinical characteristics, and patients in the top 10 CMG+ groups were included in the cohort. EXPOSURES: The examined health system factors were (1) number of primary attending physicians seen by a patient, (2) number of attending medical teams seen by a patient, (3) structure of the medical team, and (4) day of the week. MAIN MEASURES: The primary outcome was the total number of routine laboratory tests ordered on a patient during their admission. Statistical models were adjusted for age, sex, length of stay, Charlson comorbidity index, and CMG+ group. RESULTS: The final cohort consisting of 36,667 patient-days in hospital (mean (SD) age 62.5 (18.4) years) represented 5071 unique hospitalizations and 4324 unique patients. Routine laboratory test use was increased when patients saw multiple attending physicians; with an adjusted incidence rate ratio (IRR) of 1.46 (95% CI, 1.37-1.55) for two attending physicians, and 2.50 (95% CI, 2.23-2.79) for three or more attending physicians compared to a single attending physician. The number of routine laboratory tests was slightly lower on weekends (IRR 0.98, 95% CI, 0.96-0.99) and on teams without a senior resident as part of their team structure (IRR 0.89, 95% CI 0.830.96). CONCLUSIONS: The associations observed in this study suggest that breaks in continuity of care, including increased frequency in patient transfer of care, may impact the utilization of routine laboratory tests.

Correction to: Internal Medicine Point of Care Ultrasound: Indicators It's Here to Stay.

This editorial, "Internal Medicine Point of Care Ultrasound: Indicators It's Here to Stay" (DOI: 10.1007/s11606-019-05268-0), was intended to accompany "Education Indicators for Internal Medicine Point-of-Care Ultrasound: a Consensus Report from the Canadian Internal Medicine Ultrasound (CIMUS) Group".

Expert Recommendations on Frequency of Utilization of Common Laboratory Tests in Medical Inpatients: a Canadian Consensus Study.

BACKGROUND: Repetitive inpatient laboratory testing in the face of clinical stability is a marker of low-value care. However, for commonly encountered clinical scenarios on medical units, there are no guidelines defining appropriate use criteria for laboratory tests. OBJECTIVE: This study seeks to establish consensus-based recommendations for the utilization of common laboratory tests in medical inpatients. DESIGN: This study uses a modified Delphi method. Participants completed two rounds of an online survey to determine appropriate testing frequencies for selected laboratory tests in commonly encountered clinical scenarios. Consensus was defined as agreement by at least 80% of participants. PARTICIPANTS: Participants were 36 experts in internal medicine across Canada defined as internists in independent practice for ≥ 5 years with experience in medical education, quality improvement, or both. Experts represented 8 of the 10 Canadian provinces and 13 of 17 academic institutions. MAIN MEASURES: Laboratory tests and clinical scenarios included were those that were considered common on medical units. The final survey contained a total of 45 clinical scenarios looking at the utilization of six laboratory tests (complete blood count, electrolytes, creatinine, urea, international normalized ratio, and partial thromboplastin time). The possible frequency choices were every 2-4 h, 6-8 h, twice a day, daily, every 2-3 days, weekly, or none unless there was specific diagnostic suspicion. These scenarios were reviewed by two internists with training in quality improvement and survey methods. KEY RESULTS: Of the 45 initial clinical scenarios included, we reached consensus on 17 scenarios. We reached weak consensus on an additional 19 scenarios by combining two adjacent frequency categories. CONCLUSIONS: A Canadian expert panel of internists has provided frequency recommendations on the utilization of six common laboratory tests in medical inpatients. These recommendations need validation in prospective studies to assess whether restrictive versus liberal laboratory test ordering impacts patient outcomes.

Education Indicators for Internal Medicine Point-of-Care Ultrasound: a Consensus Report from the Canadian Internal Medicine Ultrasound (CIMUS) Group.

BACKGROUND: Curriculum development and implementation for internal medicine point-of-care ultrasound (IM POCUS) continues to be a challenge for many residency training programs. Education indicators may provide a useful framework to support curriculum development and implementation efforts across programs in order to achieve a consistent high-quality educational experience. OBJECTIVE: This study seeks to establish consensus-based recommendations for education indicators for IM POCUS training programs in Canada. DESIGN: This consensus study uses a modified nominal group technique for voting in the initial round, followed by two additional rounds of online voting, with consensus defined as agreement by at least 80% of the participants. PARTICIPANTS: Participants were 22 leaders with POCUS and/or education expertise from 13 Canadian internal medicine residency programs across 7 provinces. MAIN MEASURES: Education indicators considered were those that related to aspects of the POCUS educational system, could be presented by a single statistical measure, were readily understood, could be reliably measured to provide a benchmark for measuring change, and represented a policy issue. We excluded a priori indicators with low feasibility, are impractical, or assess learner reactions. Candidate indicators were drafted by two academic internists with post-graduate training in POCUS and medical education. These indicators were reviewed by two internists with training in quality improvement prior to presentation to the expert participants. KEY RESULTS: Of the 52 candidate education indicators considered, 6 reached consensus in the first round, 12 in the second, and 4 in the third round. Only 5 indicators reached consensus to be excluded; the remaining indicators did not reach consensus. CONCLUSIONS: The Canadian Internal Medicine Ultrasound (CIMUS) group recommends 22 education indicators be used to guide and monitor internal medicine POCUS curriculum development efforts in Canada.

The use of biomarkers and molecular methods for the earlier diagnosis of invasive aspergillosis in immunocompromised patients.

Invasive aspergillosis (IA) is an opportunistic infection that is often life threatening in the immunocompromised host. Early diagnosis is critical, especially given the efficacy and availability of several new anti-fungal therapies. Current (2008) diagnostic criteria have limited ability to detect early infection and are aimed at establishing disease. Although histopathology and culture techniques have traditionally been used to make a proven diagnosis of IA, their dependence on tissue samples and slow turnaround times hamper early confirmation of IA. Serologic detection of circulating galactomannan and 1,3-ß-D-glucan fungal biomarkers show promise for improving the diagnosis of IA, and their use is included in the EORTC/MSG diagnostic criteria for IA. Numerous studies have evaluated the diagnostic performance of these two biomarkers and shown that they have suboptimal sensitivity when used alone for early diagnosis of proven IA. Currently available molecular assays also suffer from a lack of standardization. Evaluation of the use of different combinations of test methods to enhance diagnostic accuracy is also being done but prompt, accurate diagnosis of IA remains a clinical and diagnostic challenge. The clinical validity and limitations of biomarkers and current molecular methods for the early diagnosis of IA are summarized in this review with respect to the different patient populations at risk for this serious infection.

Development and validation of a Pneumocystis jirovecii real-time polymerase chain reaction assay for diagnosis of Pneumocystis pneumonia.

BACKGROUND: Pneumocystis jirovecii (PJ), a pathogenic fungus, causes severe interstitial Pneumocystis pneumonia (PCP) among immunocompromised patients. A laboratory-developed real-time polyermase chain reaction (PCR) assay was validated for PJ detection to improve diagnosis of PCP. METHODS: Forty stored bronchoalveolar lavage (BAL) samples (20 known PJ positive [PJ+] and 20 known PJ negative [PJ-]) were initially tested using the molecular assay. Ninety-two sequentially collected BAL samples were then analyzed using an immunofluorescence assay (IFA) and secondarily tested using the PJ real-time PCR assay. Discrepant results were resolved by retesting BAL samples using another real-time PCR assay with a different target. PJ real-time PCR assay performance was compared with the existing gold standard (ie, IFA) and a modified gold standard, in which a true positive was defined as a sample that tested positive in two of three methods in a patient suspected to have PCP. RESULTS: Ninety of 132 (68%) BAL fluid samples were collected from immunocompromised patients. Thirteen of 92 (14%) BALs collected were PJ+ when tested using IFA. A total of 40 BAL samples were PJ+ in the present study including: all IFA positive samples (n=13); all referred PJ+ BAL samples (n=20); and seven additional BAL samples that were IFA negative, but positive using the modified gold standard. Compared with IFA, the PJ real-time PCR had sensitivity, specificity, and positive and negative predictive values of 100%, 91%, 65% and 100%, respectively. Compared with the modified gold standard, PJ real-time PCR had a sensitivity, specificity, and positive and negative predictive values of 100%. CONCLUSION: PJ real-time PCR improved detection of PJ in immunocompromised patients.

HISTORIQUE: Le Pneumocystis jirovecii (PJ), un champignon pathogène, provoque une grave pneumonie à Pneumocystis interstitielle (PPC) chez les patients immunodéprimés. Les chercheurs ont validé un test de réaction en chaîne par polymérase (PCR) en temps réel pour détecter le PJ et ainsi améliorer le diagnostic de PPC. MÉTHODOLOGIE: Les chercheurs ont d'abord vérifié 40 prélèvements de liquide bronchoalvéolaire (LBA) entreposés (20 cas positifs connus au PJ [PJ+] et 20 cas négatifs connus au PJ [PJ−]) au moyen du test moléculaire. Ils ont ensuite analysé 92 prélèvements séquentiels de LBA au moyen d'un test par immunofluorescence (IFA), puis d'un test de PCR en temps réel du PJ. Ils ont résolu les résultats divergents au moyen d'un nouveau test par PCR en temps réel des prélèvements de LBA axée sur une autre cible. Ils ont comparé le résultat du test de PCR en temps réel du PJ à la référence absolue (l'IFA) et à une référence modifiée, dans laquelle un véritable cas positif désignait un prélèvement positif par deux méthodes sur trois chez un patient atteint d'une PPC présumée. RÉSULTATS: Quatre-vingt-dix prélèvements de LBA (68 %) sur 132 provenaient de patients immunodéprimés. Treize prélèvements de LBA (14 %) sur 92 étaient PJ+ d'après l'IFA. Dans la présente étude, 40 prélèvements de LBA étaient PJ+, y compris tous les prélèvements positifs à l'IFA (n=13), tous les prélèvements de LBA PJ+ aiguillés (n=20) et sept autres prélèvements de LBA négatifs à l'IFA, mais positifs selon la référence modifiée. Par rapport à l'IFA, la PCR en temps réel du PJ avait une sensibilité, une spécificité et des valeurs prédictives positive et négative de 100 %, 91 %, 65 % et 100 %, respectivement. Par rapport à la référence modifiée, la PCR en temps réel du PJ avait une sensibilité, une spécificité et des valeurs prédictives positive et négative de 100 %. CONCLUSION: La PCR en temps réel du PJ en améliore la détection chez les patients immunodéprimés.

Pragmatic randomised trial assessing the impact of peer comparison and therapeutic recommendations, including repetition, on antibiotic prescribing patterns of family physicians across British Columbia for uncomplicated lower urinary tract infections.

OBJECTIVE: To evaluate the impact of a personalised audit and feedback prescribing report (AF) and brief educational summary (ES) on empiric treatment of uncomplicated lower urinary tract infections (UTIs) by family physicians (FPs). DESIGN: Cluster randomised control trial. SETTING: The intervention was conducted in British Columbia, Canada between 23 September 2021 and 28 March 2022. PARTICIPANTS: We randomised 5073 FPs into a standard AF and ES intervention arm (n=1691), an ES-only arm (n=1691) and a control arm (n=1691). INTERVENTIONS: The AF contained personalised and peer-comparison data on first-line antibiotic prescriptions for women with uncomplicated lower UTI and key therapeutic recommendations. The ES contained detailed, evidence-based UTI management recommendations, incorporated regional antibiotic resistance data and recommended nitrofurantoin as a first-line treatment. MAIN OUTCOME MEASURES: Nitrofurantoin as first-line pharmacological treatment for uncomplicated lower UTI, analysed using an intention-to-treat approach. RESULTS: We identified 21 307 cases of uncomplicated lower UTI among the three trial arms during the study period. The impact of receiving both the AF and ES increased the relative probability of prescribing nitrofurantoin as first-line treatment for uncomplicated lower UTI by 28% (OR 1.28; 95% CI 1.07 to 1.52), relative to the delay arm. This translates to additional prescribing of nitrofurantoin as first-line treatment, instead of alternates, in an additional 8.7 cases of uncomplicated UTI per 100 FPs during the 6-month study period. CONCLUSION: AF prescribing data with educational materials can improve primary care prescribing of antibiotics for uncomplicated lower UTI. TRIAL REGISTRATION NUMBER: NCT05817253.

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.

Association between physician continuity of care and patient outcomes in clinical teaching units: a cohort analysis.

BACKGROUND: Hospital-based clinical teaching units (CTUs) are supervised by rotating attending physicians. Physician hand-offs in other contexts have been associated with worse patient outcomes, presumably through communication gaps. We aimed to determine the association between attending physician hand-offs on CTUs and patient outcomes including escalation of care, readmission and mortality. METHODS: We conducted a retrospective, multicentre cohort study using data from 3 tertiary care hospitals in Calgary between Jan. 1, 2015, and Dec. 31, 2017. We included hospital admissions in the top 10 case-mix groups. Our exposure variable was the number of attending physicians seen by a patient. Outcome measures were admission to intensive care unit (ICU); inpatient 7- and 30-day mortality; and 7- and 30-day readmission rate. We used multivariable regression statistical models adjusted for patient age, sex, length of stay, Charlson Comorbidity Index, case-mix groups, senior resident presence, team handovers and team transfers. RESULTS: Our cohort included 4324 unique patients. There were no significant differences in the incidence rate ratios (IRRs) of admission to ICU, inpatient 7- and 30-day mortality, and 7- and 30-day readmission rates among 1 or 2 physicians. However, we noted a significant increase in 30-day readmission rate (IRR 1.37, 95% confidence interval 1.05-1.78) in patients who had 3 or more attending physicians compared with those who had 1 attending physician. INTERPRETATION: We found that 2 or more physician hand-offs on CTUs had a modestly greater association with patient readmission at 30 days. More research is needed to explore this finding and to evaluate associated patient and resource outcomes with physician hand-offs.

Working together in health research: a mixed-methods patient engagement evaluation.

BACKGROUND: In patient-oriented research (POR), patients contribute their valuable knowledge and lived-experiences to work together as active research partners at all stages of the health research cycle. However, research looking to understand how patient research partners (PRPs) and researchers work together in meaningful and collaborative ways remains limited. This study aims to evaluate patient engagement with the RePORT Patient Advisory Council (PAC) and to identify barriers and facilitators to meaningful patient engagement encountered within research partnerships involving patient research partners and researchers. METHODS: The RePORT PAC members included nine PRPs and nine researchers (clinician-researchers, research staff, patient engagement experts) from both Alberta and British Columbia. All members were contacted and invited to complete an anonymous online survey (Public and Patient Engagement Evaluation (PPEET) tool) at two different project times points. The PAC was invited for a semi-structured interview to gain in-depth understanding of their experiences working together. Interviews were audio-recorded, transcribed, and the data was thematically analyzed with the support of a qualitative analysis software, NVivo. RESULTS: A total of nine PRPs (100%) and three researchers (33%) participated in the baseline survey in February 2022 while six PRPs (67%) responded and three researchers (33%) completed the follow up survey in May 2022. For the semi-structured interviews, nine PRPs (100%) and six researchers (67%) participated. According to the survey results, PAC members agreed that the supports (e. g. training, compensation) needed to contribute to the project were available throughout the project. The survey responses also showed that most members of the PAC felt their opinions and views were heard. Responses to the survey regarding diversity within the PAC were mixed. There were many suggestions for improving diversity and collaboration provided by PAC members during the semi-structured interviews. PAC members mentioned that PAC PRPs informed the co-development of research materials such as recruitment posters and interview guides for the RePORT study. CONCLUSIONS: Through fostering a collaborative environment, we can engage a diverse group of people to work together meaningfully in health research. We have identified what works well, and areas for improvement within our research partnership involving PRPs and researchers as well as recommendations for POR projects more broadly, going forward.

Patient research partners contribute their valuable knowledge, lived experiences, and skills in health research projects. However, research looking to understand how patient partners and researchers can work together in a meaningful and collaborative way remains limited. We aim to evaluate patient engagement with the RePORT Patient Advisory Council (PAC) and to identify barriers and facilitators to meaningful patient engagement encountered within research partnerships involving patient research partners and researchers. We used a mixed methods design as it provided the opportunity to gather more insights from the RePORT PAC members' engagement experiences throughout the study and provide a deeper understanding on the barriers and facilitators to working together. We involved diverse patient research partners, clinicians/researchers, patient engagement organization team members and other stakeholders from the RePORT PAC. All PAC members were invited to complete an anonymous online survey as well as a semi-structured interview. Patient research partners appreciated the supports (e.g. training, compensation) provided throughout the project. Most PAC members felt that their views and opinions were heard, which further facilitated a collaborative team environment. There were many suggestions for improving diversity and collaboration provided by PAC members during the semi-structured interviews. Through fostering a collaborative environment, we can engage a diverse group of people to work together meaningfully in health research. We have identified what works well, and areas for improvement in our research partnership and recommendations for patient-oriented research projects more broadly, going forward.

Acute severe hepatitis as a presenting symptom in clinically stable patients admitted with SARS-CoV-2 Omicron infection.

BACKGROUND: Suggested mechanisms for SARS-CoV-2 direct liver infection have been proposed by others to involve both cholangiocytes and hepatocytes. Early clinical studies have highlighted abnormal liver biochemistry with COVID-19 infection as often not being severe, with elevated liver enzymes <5X the upper limit of normal. METHODS: Liver enzymes were evaluated and compared in patients admitted with a diagnosis of COVID-19 in a deidentified Internal Medicine-Medical Teaching Unit/hospitalist admission laboratory database. Comparisons in the incidence of severe liver injury (alanine aminotransferase >10 times upper limit of normal) were made for patients with pre-Omicron SARS-CoV-2 (November 30, 2019, to December 15, 2021) and Omicron SARS-CoV-2 (December 15, 2021, to April 15, 2022). Comprehensive hospital health records were also reviewed for the 2 patient cases discussed. One patient had a liver biopsy that was evaluated with H&E and immunohistochemistry staining using an antibody against COVID-19 spike protein. RESULTS: The evaluation of a deidentified admissions laboratory database found the incidence of severe liver injury was 0.42% with Omicron versus 0.30% with pre-Omicron variants of COVID-19. In both patient cases discussed, abnormal liver biochemistry and a negative comprehensive workup strongly suggest COVID-19 as the cause of severe liver injury. In the one patient with liver biopsy, immunohistochemistry staining suggests SARS-CoV-2 presence in the portal and lobular spaces in association with immune cell infiltration. CONCLUSIONS: The Omicron variant of SARS-CoV-2 should be considered in the differential diagnosis of severe acute liver injury. Our observation suggests that this new variant, either through direct liver infection and/or mediating immune dysfunction, can result in severe liver injury.

Sequential measurement of the neurosensory retina in hypertensive disorders of pregnancy: a model of microvascular injury in hypertensive emergency.

Optical coherence tomography of the eye suggests the retina thins in normal pregnancy. Our objectives were to confirm and extend these observations to women with hypertensive disorders of pregnancy (HDP). Maternal demographics, clinical/laboratory findings and measurements of macular thickness were repeatedly collected at gestational ages <20 weeks, 20-weeks to delivery, at delivery and postpartum. The primary outcome was the change in macular thickness from non-pregnant dimensions in women with incident HDP compared to non-hypertensive pregnant controls. Secondary outcomes were the relationship(s) between mean arterial pressure (MAP) and macular response. Data show macular thicknesses diminished at <20 weeks gestation in each of 27 pregnancies ending in HDP (mean 3.94 µm; 95% CI 4.66, 3.21) and 11 controls (mean 3.92 µm; 5.05, 2.79; P < 0.001 versus non-pregnant dimensions in both; P = 0.983 HDP versus controls). This thinning response continued to delivery in all controls and in 7 women with HDP superimposed on chronic hypertension. Macular thinning was lost after 20 weeks gestation in the other 20 women with HDP. MAP at loss of macular thinning in women without prior hypertension (n = 12) was identical to MAP at enrollment. However, mean MAP subsequently rose 19 mmHg (15, 22) leading to de novo HDP in all 12 women. Loss of thinning leading to a rise in MAP was also observed in 8 of 15 women with HDP superimposed on chronic hypertension. We conclude the macula thins in most women in early pregnancy. Those who lose this early macular thinning response often develop blood pressure elevations leading to HDP.

Repurposing the Ordering of Routine Laboratory Tests in Hospitalised Medical Patients (RePORT): results of a cluster randomised stepped-wedge quality improvement study.

BACKGROUND: Low-value use of laboratory tests is a global challenge. Our objective was to evaluate an intervention bundle to reduce repetitive use of routine laboratory testing in hospitalised patients. METHODS: We used a stepped-wedge design to implement an intervention bundle across eight medical units. Our intervention included educational tools and social comparison reports followed by peer-facilitated report discussion sessions. The study spanned October 2020-June 2021, divided into control, feasibility testing, intervention and a follow-up period. The primary outcomes were the number and costs of routine laboratory tests ordered per patient-day. We used generalised linear mixed models, and analyses were by intention to treat. RESULTS: We included a total of 125 854 patient-days. Patient groups were similar in age, sex, Charlson Comorbidity Index and length of stay during the control, intervention and follow-up periods. From the control to the follow-up period, there was a 14% (incidence rate ratio (IRR)=0.86, 95% CI 0.79 to 0.92) overall reduction in ordering of routine tests with the intervention, along with a 14% (ß coefficient=-0.14, 95% CI -0.07 to -0.21) reduction in costs of routine testing. This amounted to a total cost savings of $C1.15 per patient-day. There was also a 15% (IRR=0.85, 95% CI 0.79, 0.92) reduction in ordering of all common tests with the intervention and a 20% (IRR=1.20, 95% CI 1.10 to 1.30) increase in routine test-free patient-days. No worsening was noted in patient safety endpoints with the intervention. CONCLUSIONS: A multifaceted intervention bundle using education and facilitated multilevel social comparison was associated with a safe and effective reduction in use of routine daily laboratory testing in hospitals. Further research is needed to understand how system-level interventions may increase this effect and which intervention elements are necessary to sustain results.

A conditional allele of Rspo3 reveals redundant function of R-spondins during mouse limb development.

R-spondins are secreted ligands that bind cell surface receptors and activate Wnt/ß-catenin signaling. Human mutations and gene inactivation studies in mice have revealed a role for these four proteins (RSPO1-4) in diverse developmental processes ranging from sex determination to limb development. Among the genes coding for R-spondins, only inactivation of Rspo3 shows early embryonic lethality (E10.5 in mice). Therefore, a conditional allele of this gene is necessary to understand the function of R-spondins throughout murine development. To address this need, we have produced an allele in which loxP sites flank exons 2-4 of Rspo3, allowing tissue-specific deletion of these exons in the presence of Cre recombinase. We used these mice to investigate the role of Rspo3 during limb development and found that limbs ultimately developed normally in the absence of Rspo3 function. However, severe hindlimb truncations resulted when Rspo3 and Rspo2 mutations were combined, demonstrating redundant function of these genes.

Impact of an education and multilevel social comparison-based intervention bundle on use of routine blood tests in hospitalised patients at an academic tertiary care hospital: a controlled pre-intervention post-intervention study.

BACKGROUND: Repetitive inpatient laboratory testing contributes to waste in healthcare. We evaluated an intervention bundle combining education and multilevel social comparison feedback to safely reduce repetitive use of inpatient routine laboratory tests. METHODS: This non-randomised controlled pre-intervention post-intervention study was conducted in four adult hospitals from October 2016 to March 2018. In the medical teaching unit (MTU) of the intervention site, learners received education and aggregate social comparison feedback and attending internists received individual comparison feedback on routine laboratory test utilisation. MTUs of the remaining three sites served as control units. Number and cost of routine laboratory tests ordered per patient-day before and after the intervention was compared with the control units, adjusting for patient factors. Safety endpoints included number of critically abnormal laboratory test results, number of stat laboratory test orders, patient length of stay, transfer rate to the ICU, and 30-day readmission and mortality. RESULTS: A total of 14 000 patients were included. Pre-intervention and post-intervention groups were similar in age, sex, Charlson Comorbidity Index and length of stay. From the pre-intervention period to the post-intervention period, significantly fewer routine laboratory tests were ordered at the intervention MTU (incidence rate ratio=0.89; 95% CI 0.79 to 1.00; p=0.048) with associated costs savings of $C68 877 (p=0.020) as compared with the control sites. The variability in the ordering pattern of internists at the intervention site also decreased post-intervention. No worsening was noted in the safety endpoints between the pre-intervention and post-intervention period at the intervention unit compared with the controls. CONCLUSIONS: Combination of education and multilevel social comparison feedback significantly and safely led to cost savings through reduced use of routine laboratory tests in hospitalised patients.

Disseminated cerebral aspergillosis complicated by thrombotic microangiopathy.

Invasive aspergillosis (IA) is a serious condition that can affect almost any organ. Cerebral aspergillosis itself is rapidly fatal without treatment. We report a case of disseminated cerebral IA in a patient exposed to cyclophosphamide, rituximab and prednisone. This case is unique because: 1) disseminated IA has not been described in anti-glomerular basement membrane glomerulonephritis; 2) IA led to thrombotic microangiopathy with normal ADAMTS13 and 3) voriconazole toxicity necessitated use of isavuconazole for IA treatment.

Carbon pricing: a win-win environmental and public health policy.

Carbon pricing is an important tool for mitigating climate change. Carbon pricing can have significant health co-benefits. Air pollution from fossil fuels leads to detrimental health effects, including premature mortality, heart attacks, hospitalization from cardiorespiratory conditions, stroke, asthma exacerbations, and absenteeism from school and work, and may also be linked to autism spectrum disorder and Alzheimer's disease. Reduction in fossil fuel combustion through a carbon price can lead to improvements in all these areas of health. It can also improve health by encouraging active transportation choices and improving ecosystems. Furthermore, it can promote health equity in society and improve overall societal health where the revenue from carbon pricing is used as a progressive redistribution mechanism for low-income households. Hence, carbon pricing is a win-win environmental and public health policy and an important step toward achieving Canada's emission target by 2030. However, carbon pricing has several potential pitfalls which need to be considered in the design and implementation of any such policy. As Canada moves ahead with mandatory carbon pricing this fall, it is important to monitor its impact, evaluate it objectively, and modify and complement as necessary with policies and regulations.