A 62-year-old man with a history of hypertension presented with 12 h of lip and facial swelling. Twelve days prior to presentation, he developed fevers (up to 39 C), chills, fatigue, myalgias, anorexia, anosmia, ageusia, and a dry cough. These symptoms were improving aside from a lingering dry cough. He noticed upper lip swelling the night prior to presentation, which progressed to include swelling of his cheeks and lower face. He did not experience concomitant rash, pruritus, or shortness of breath. Medications prior to admission included amlodipine and lisinopril, without recent dosing changes and which he had tolerated for 10 years. He had no personal or family history of angioedema.On examination, he was normotensive with a room air oxygen saturation of 99%. He was breathing comfortably without stridor. Compared with his usual state (Panel A), he had slightly asymmetric, non-pitting oedema of his cheeks and lips (Panel B). He had no other sites of swelling and had no rash. Reverse transcription-PCR was positive for SARS-CoV-2. Other laboratory findings included leukocytosis with relative lymphopenia and elevated high-sensitivity C-reactive protein and D-dimer. Functional C1 inhibitor levels (59.7 mg/dL), C3 levels (206 mg/dL), and C4 levels (46 mg/dL) were all elevated (Supplementary material online, Table S1). Computed tomography imaging of his chest showed patchy ground-glass opacities with subpleural and bronchovascular distribution. On presentation, he received intravenous methylprednisolone, famotidine, and diphenhydramine. His lisinopril was held. By hospital day 2, the patient's swelling markedly improved (Panel C) and he was discharged home in stable condition.Vascular permeability is a proposed pathological feature of COVID-19, and the dry cough has been remarked to resemble the idiopathic cough seen in 10-15% of patients who receive angiotensin-converting enzyme (ACE) inhibitors. Both ACE inhibitor-induced cough and certain forms of angioedema are thought to be bradykinin dependent. Bradykinin and its metabolites are cleaved by a series of enzymes, including ACE and its homologue ACE2. After SARS-CoV-2 gains cellular entry by binding to ACE2, it results in down-regulation of surface ACE2, impairing its role in the breakdown of several substrates, including bradykinin metabolites. While late-onset angioedema during chronic ACE inhibition is rarely observed, SARS-CoV-2-mediated dysregulation of ACE2 may represent a 'second hit' that contributed to angioedema in this case. As preclinical models have suggested that bradykinin receptor signalling may be a factor in facilitating pulmonary injury and inflammation, modulation of this pathway should be explored as a potential therapeutic option in COVID-19.

Background Gaps between rational thought and actual decisions are increasingly recognized as a reason why people make suboptimal choices in states of heightened emotion, such as stress. These observations may help explain why high-risk medications continue to be prescribed to acutely ill hospitalized older adults despite widely accepted recommendations against these practices. Role playing and other efforts, such as simulation training, have demonstrated benefits to help people avoid decisional gaps but have not been tested to reduce overprescribing of high-risk medications. Objective This study aims to evaluate the impact of a simulation-based training program designed to address decisional gaps on prescribing of high-risk medications compared with control. Methods In this 2-arm pragmatic trial, we are randomizing at least 36 first-year medical resident physicians (ie, interns) who provide care on inpatient general medicine services at a large academic medical center to either intervention (simulation-based training) or control (online educational training). The intervention comprises a 40-minute immersive individual simulation training consisting of a reality-based patient care scenario in a simulated environment at the beginning of their inpatient service rotation. The simulation focuses on 3 types of high-risk medications, including benzodiazepines, antipsychotics, and sedative hypnotics (Z-drugs), in older adults, and is specifically designed to help the physicians identify their reactions and prescribing decisions in stressful situations that are common in the inpatient setting. The simulation scenario is followed by a semistructured debriefing with an expert facilitator. The trial’s primary outcome is the number of medication doses for any of the high-risk medications prescribed by the interns to patients aged 65 years or older who were not taking one of the medications upon admission. Secondary outcomes include prescribing by all providers on the care team, being discharged on 1 of the medications, and prescribing of related medications (eg, melatonin, trazodone), or the medications of interest for the control intervention. These outcomes will be measured using electronic health record data. Results Recruitment of interns began on March 29, 2021. Recruitment for the trial ended in Q42021, with follow-up completed by Q12022. Conclusions This trial will evaluate the impact of a simulation-based training program designed using behavioral science principles on prescribing of high-risk medications by junior physicians. If the intervention is shown to be effective, this approach could potentially be reproducible by others and for a broader set of behaviors. Trial Registration ClinicalTrials.gov NCT04668248; https://clinicaltrials.gov/ct2/show/NCT04668248 International Registered Report Identifier (IRRID) PRR1-10.2196/31464

Background Chronic kidney disease (CKD) is associated with an increased risk of pulmonary hypertension, which may lead to right ventricular (RV) pressure overload and RV dysfunction. However, the presence of subclinical changes in RV structure or function in early CKD and the influence of these changes on mortality are not well studied. We hypothesized that early CKD, as indicated by elevated albuminuria or mild reductions in estimated glomerular filtration rate (eGFR), is associated with greater RV dilation and RV mass. Methods We included 4,063 participants (age, 45–84 years) without baseline clinical cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis. The associations of baseline creatinine–cystatin C-based eGFR and albuminuria with cardiac magnetic resonance-derived RV measures (2000–2002) were examined cross-sectionally with linear regression models. Cox regression models were used to examine whether RV parameters modified the associations of eGFR and albuminuria with all-cause mortality. Results Participants with reductions in eGFR primarily within the 60–89 mL/min/1.73 m2 category had smaller RV end-diastolic and end-systolic volumes and stroke volume (all adjusted P-trends <0.001) than those with eGFR ≥90 mL/min/1.73 m2, an association that was predominantly seen in participants with albuminuria below 30 mg/g creatinine. Albuminuria was more strongly associated with death among those with lower RV volumes (P-values for interaction <0.03). Conclusions Among community-dwelling adults, reductions in eGFR primarily within the normal range were associated with smaller RV volumes and the association of albuminuria with worse survival was stronger among those with smaller RV volumes. Further studies are needed to elucidate the underlying mechanistic pathways that link kidney measures and RV morphology.