The MedSafer Study-Electronic Decision Support for Deprescribing in Hospitalized Older Adults: A Cluster Randomized Clinical Trial.

IMPORTANCE: Scalable deprescribing interventions may reduce polypharmacy and the use of potentially inappropriate medications (PIMs); however, few studies have been large enough to evaluate the impact that deprescribing may have on adverse drug events (ADEs). OBJECTIVE: To evaluate the effect of an electronic deprescribing decision support tool on ADEs after hospital discharge among older adults with polypharmacy. DESIGN, SETTING, AND PARTICIPANTS: This was a cluster randomized clinical trial of older (≥65 years) hospitalized patients with an expected survival of more than 3 months who were admitted to 1 of 11 acute care hospitals in Canada from August 22, 2017, to January 13, 2020. At admission, participants were taking 5 or more medications per day. Data analyses were performed from January 3, 2021, to September 23, 2021. INTERVENTIONS: Personalized reports of deprescribing opportunities generated by MedSafer software to address usual home medications and measures of prognosis and frailty. Deprescribing reports provided to the treating team were compared with usual care (medication reconciliation). MAIN OUTCOMES AND MEASURES: The primary outcome was a reduction of ADEs within the first 30 days postdischarge (including adverse drug withdrawal events) captured through structured telephone surveys and adjudicated blinded to intervention status. Secondary outcomes were the proportion of patients with 1 or more PIMs deprescribed at discharge and the proportion of patients with an adverse drug withdrawal event (ADWE). RESULTS: A total of 5698 participants (median [range] age, 78 [72-85] years; 2858 [50.2%] women; race and ethnicity data were not collected) were enrolled in 3 clusters and were adjudicated for the primary outcome (control, 3204; intervention, 2494). Despite cluster randomization, there were group imbalances, eg, the participants in the intervention arm were older and had more PIMS prescribed at baseline. After hospital discharge, 4989 (87.6%) participants completed an ADE interview. There was no significant difference in ADEs within 30 days of discharge (138 [5.0%] of 2742 control vs 111 [4.9%] of 2247 intervention participants; adjusted risk difference [aRD] -0.8%; 95% CI, -2.9% to 1.3%). Deprescribing increased from 795 (29.8%) of 2667 control to 1249 (55.4%) of 2256 intervention participants [aRD, 22.2%; 95% CI, 16.9% to 27.4%]. There was no difference in ADWEs between groups. Several post hoc sensitivity analyses, including the use of a nonparametric test to address the low cluster number, group imbalances, and potential biases, did not alter study conclusions. CONCLUSIONS AND RELEVANCE: This cluster randomized clinical trial showed that providing deprescribing clinical decision support during acute hospitalization had no demonstrable impact on ADEs, although the intervention was safe and led to improvements in deprescribing. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03272607.

Case Report: Segmental Arterial Mediolysis, a Rare Cause of Hypertension.

RATIONALE: The differential diagnosis for hypertension with elevated plasma renin is broad. This case illustrates one of the rarer, and therefore underrecognized, causes of high renin hypertension. PRESENTING CONCERNS OF THE PATIENT: A 41-year-old man with a medical history significant for multiple ischemic strokes and dyslipidemia presented for assessment of decreased renal function and resistant hypertension. His initial workup for secondary causes of hypertension was remarkable for an elevated plasma renin and normal aldosterone. Further investigation with computed tomography (CT) angiography was performed, which demonstrated multiple bilateral renal aneurysms and infarcts. DIAGNOSES: After ruling out other potential causes of bilateral renal aneurysms and infarcts, a diagnosis of segmental arterial mediolysis (SAM) was made. INTERVENTIONS: Optimization of antihypertensive regimen, counseling regarding regular home blood pressure monitoring, and smoking cessation. OUTCOMES: The patient achieved excellent blood pressure control, stable renal function, and had no further strokes or other vascular events. TEACHING POINTS: Our case demonstrates the importance of considering SAM in the diagnosis of hypertension with elevated plasma renin and as a vasculitis mimic. It also highlights the importance of considering renal vascular imaging in the workup of resistant hypertension.

JUSTIFICATION: Le diagnostic différentiel de l'hypertension avec élévation des concentrations plasmatiques de rénine est vaste. Le cas présenté illustre une des causes les plus rares et les moins connues de cette forme d'hypertension. PRÉSENTATION DU CAS: Un patient de 41 ans dont les antécédents médicaux montraient des dyslipidémies et des accidents ischémiques cérébraux multiples s'est présenté pour une réduction de la fonction rénale et une hypertension résistante. Le premier bilan des causes secondaires de l'hypertension se distinguait par une concentration plasmatique élevée de rénine et une aldostérone normale. L'angiographie par tomodensitométrie a révélé de multiples anévrismes et infarctus rénaux bilatéraux. DIAGNOSTIC: Après avoir écarté les autres causes potentielles d'anévrismes et d'infarctus rénaux bilatéraux, un diagnostic de médiolyse artérielle segmentaire a été posé. INTERVENTIONS: Optimisation du traitement antihypertenseur, encadrement quant à la surveillance régulière de la pression artérielle à domicile et abandon du tabac. RÉSULTATS: Le patient a réussi à contrôler sa pression artérielle, sa fonction rénale s'est stabilisée et aucun autre événement vasculaire n'est survenu. LEÇONS TIRÉES: Ce cas souligne l'importance d'envisager la médiolyse artérielle segmentaire comme affection analogue de la vascularite, et d'en tenir compte dans le diagnostic de l'hypertension avec élévation de la concentration plasmatique de rénine. Ce cas insiste également sur l'importance de considérer l'imagerie vasculaire rénale dans l'étude de l'hypertension résistante.

Renal infarct in a COVID-19-positive kidney-pancreas transplant recipient.

The novel coronavirus disease 2019 (COVID-19) is associated with increased risk of thromboembolic events, but the extent and duration of this hypercoagulable state remain unknown. We describe the first case report of renal allograft infarction in a 46-year-old kidney-pancreas transplant recipient with no prior history of thromboembolism, who presented 26 days after diagnosis of COVID-19. At the time of renal infarct, he was COVID-19 symptom free and repeat test for SARS-CoV-2 was negative. This case report suggests that a hypercoagulable state may persist even after resolution of COVID-19. Further studies are required to determine thromboprophylaxis indications and duration in solid organ transplant recipients with COVID-19.

Weaver Syndrome-Associated EZH2 Protein Variants Show Impaired Histone Methyltransferase Function In Vitro.

Weaver syndrome (WS) is a rare congenital disorder characterized by generalized overgrowth, macrocephaly, specific facial features, accelerated bone age, intellectual disability, and susceptibility to cancers. De novo mutations in the enhancer of zeste homolog 2 (EZH2) have been shown to cause WS. EZH2 is a histone methyltransferase that acts as the catalytic agent of the polycomb-repressive complex 2 (PRC2) to maintain gene repression via methylation of lysine 27 on histone H3 (H3K27). Functional studies investigating histone methyltransferase activity of mutant EZH2 from various cancers have been reported, whereas WS-associated mutations remain poorly characterized. To investigate the role of EZH2 in WS, we performed functional studies using artificially assembled PRC2 complexes containing mutagenized human EZH2 that reflected the codon changes predicted from patients with WS. We found that WS-associated amino acid alterations reduce the histone methyltransferase function of EZH2 in this in vitro assay. Our results support the hypothesis that WS is caused by constitutional mutations in EZH2 that alter the histone methyltransferase function of PRC2. However, histone methyltransferase activities of different EZH2 variants do not appear to correlate directly with the phenotypic variability between WS patients and individuals with a common c.553G>C (p.Asp185His) polymorphism in EZH2.

Microbiological survey of imported produce available at retail across Canada.

Increasing consumption and year-round consumer demand for fresh, minimally processed green vegetables have been observed in Canada and other developed countries. However, in the past two decades, produce has been increasingly implicated in outbreaks and correspondingly recognized as a vector for the transmission of pathogenic microorganisms. To this end, we examined the microbiological quality of imported produce available at retail across Canada during a period of limited domestic availability. In total, 106 samples obtained from five Canadian cities were purchased from retail outlets and subjected to microbiological analyses, including aerobic plate (APC) and coliform counts, and enrichments for enterococci, indicator Escherichia coli, E. coli O157:H7 and Salmonella spp. Also, recovered Enterococcus faecalis and Enterococcus faecium were screened for antimicrobial resistance (AMR). Overall, samples included herbs (n=61), leafy greens (n=25), and spinach (n=20) deriving from five countries (Columbia, Dominican Republic, Guatemala, Mexico, and the United States [US]). APCs were consistent across commodities regardless of country, ranging from mean log10 CFU/g of 6.1 to 7.4, with no significant differences observed. Excluding a single leafy green sample from Guatemala, the lowest prevalence of coliforms was for Mexican herbs (22.2%), with a high of 66.7% on US leafy greens. With the exception of spinach, concentrations of coliforms varied widely, ranging from undetectable to too numerous to count (>8.5 log10 CFU/g). Of the commodities assessed, Mexican and US spinach had the lowest coliform concentrations (undetectable to 4.0 log10 CFU/g). Organic herbs and conventional leafy greens possessed significantly lower (p<0.05) prevalence of coliforms compared to conventional herbs and organic leafy greens, respectively. The most frequent recovery of indicator E. coli was observed for herbs, with 11.1, 8.3, and 3.7% prevalence observed in samples from Columbia, US, and Mexico, respectively. For spinach, 0 and 6.7% of Mexican and US samples tested positive, while no leafy green samples from either country were positive. No E. coli O157:H7 or Salmonella spp. were detected. E. faecium and E. faecalis were recovered from 15.1 and 5.7% of samples, respectively. Although no glycopeptide resistance was observed, resistance to other clinically relevant antibiotics was noteworthy in both species. Overall, though microbiological quality indicators were frequently high, E. coli O157:H7 and Salmonella were not detected. However, the presence of resistance and reduced susceptibility to clinically relevant antimicrobials in recovered enterococci demonstrate imported fresh produce may serve as a vehicle for the transmission of antimicrobial resistance across national borders.