2 Minute Medicine Rewind December 27, 2021

Hypoglycemia requiring paramedic assistance among adults in southwestern Ontario, Canada: A population-based retrospective cohort study

1. Among patients who received paramedic assistance for hypoglycemic events, rates of refusal of transport to hospital were high.

2. Refusal of transport to hospital was more common in patients with mean capillary blood sugar greater than 2.5 and GCS scores above 9.

Evidence Rating Level: 2 (Good)

In Canada, approximately 23% of emergency department visits for severe hypoglycemia result in hospitalization. The rates of pre-hospital hypoglycemic events requiring paramedic assistance have not been well described in the literature and may be unknown to patients’ primary care providers. This population-based retrospective cohort study collected ambulance call report data from 2008 to 2014, comprising calls from adult patients to 8 paramedic services in southwestern Ontario to describe the incidence of hypoglycemic events and predictors of hospital transport refusals. Over the specified time period, there were 9185 patient calls for hypoglycemic events requiring paramedic intervention, of which 2243 (24%) declined transport to hospital. Canadian Triage Acuity Scale less than 3 was significantly associated with higher odds of hospital transport, adjusted OR 1.12 (0.65-1.31); as was glucagon treatment, adjusted OR 3.89 (1.64-9.20). Patients who refused hospital transport had significantly higher mean capillary blood glucose and Glasgow Coma Scale scores compared to those who did not (p<0.001). There were no significant associations between antihyperglycemic use and hospital transport. These findings may indicate that a sizable proportion of patients who decline hospital transport after milder hypoglycemic events are less willing to seek follow-up care.

Clinical characteristics and prognostic risk factors of patients with proven invasive pulmonary aspergillosis: A single-institution retrospective study

1. All-cause mortality from invasive pulmonary aspergillosis was significantly higher in patients with advanced age (>60 years), malignancy and chemotherapy history.

Evidence Rating Level: 2 (Good)

Although invasive pulmonary aspergillosis (IPA) commonly afflicts immunocompromised individuals, there is a paucity of pathological data available for diagnostic clarification. This retrospective chart review collected data from inpatients with IPA proven by pathology reports to describe patient clinical characteristics and risk factors for progression of the disease. Demographic, clinical and laboratory studies were obtained for 117 patients; out of these, 74 (63.2%) were males and 85 (72.6%) survived, with diabetes mellitus (n=30, 25.6%) as the most common comorbidity and consolidation (n=71, 60.7%) the most likely abnormality on diagnostic imaging. All-cause mortality was the primary endpoint. Patients who died were significantly more likely to have history of malignancy, recent chemotherapy and age greater than 60 years (p < 0.001). Multivariate analysis demonstrated that age (HR: 10.7, CI: 2.5-44.9, p <0.001), chemotherapy (HR: 9.5, CI: 2.7-32.9, p<0.001), pleural effusion on CT (HR: 5.74, CI:1.6-20.8,p=0.008), and CRP count (HR: 6.3, CI: 1.2-34.3, p=0.033) were independent risk factors for mortality. There were no significant differences in treatment between survival and non-survival groups. These findings may have implications for pathological investigations earlier in the disease course of IPA.

Ruxolitinib versus dexamethasone in hospitalized adults with COVID-19: multicenter matched cohort study

1. For hospitalized COVID-19 patients on respiratory support, there were no significant differences in case-fatality rates associated with dexamethasone treatment compared to ruxolitinib.

Evidence Rating Level: 2 (Good)

In patients hospitalized with COVID-19 hyperinflammatory syndrome, dexamethasone is the mainstay of mortality-reducing treatment. Ruxolitinib is a Janus kinase 1/2 inhibitor with demonstrated immunomodulatory efficacy in myelofibrosis, and in some early studies, COVID-19. This multicenter matched cohort study recruited 146 hospitalized patients on respiratory support for COVID-19 with scores of 5-6 on the Ordinal scale, and excluded those being palliated for terminal oncologic illnesses. Patients matched to the treatment arm received ruxolitinib in doses of 5-10 mg bid while reference arm patients were selected from hospitalized individuals receiving dexamethasone 16-24 mg daily due to respiratory failure. The primary outcome measures were mortality and discharge from hospital. The cumulative incidence of death and median time to discharge were 9.6% and 13 days in the treatment group, respectively, compared to 13.0% and 11 days in those receiving dexamethasone (p=0.35, OR = 0.71,CI[0.31-1.57]). The absolute risk difference was 3.4% (95% CI[-3.8, 10.7%]). Ruxolitinib was associated with case-fatality reduction in patients with persistent fevers greater than 38.5°C (OR 0.33, 95% CI 0.11-1.00), but was not superior over dexamethasone for any other features of hyperinflammatory syndrome including elevated CRP or acute kidney injury. There were no significant differences between the groups in terms of case-fatality rates across all subgroups and no differences in adverse events following administration of either dexamethasone or ruxolitinib. The evidence was insufficient to draw further conclusions on the basis of this single randomized controlled trial, though with further research, ruxolitinhib may be a viable alternative to dexamethasone for the treatment of severe COVID-19 infections.

Renal function in B-thalassemia major patients treated with two different iron-chelation regimes

1. For B-thalassemia major patients receiving iron chelation therapy, markers of renal tubular endothelial injury were higher in those treated with deferasirox compared to desferoxamine +/- deferiprone.

Evidence Rating Level: 2 (Good)

Patients with transfusion-dependent B thalassemia are reported to have renal tubular dysfunctions that may be secondary to various mechanisms including chronic anemia, hypoxia, hemosiderosis, iron chelation therapy and iron overload. Hematological and iron overload parameters in this subset of patients have not been well defined. This retrospective cohort study recruited 36 patients with transfusion-dependent B-thalassemia receiving blood transfusions every 2-3 weeks and divided into two subgroups depending upon their iron chelation therapy, either 1) deferasirox (DFX) or 2) desferoxamine (DFO) +/- deferiprone (DFP). Blood and urine samples were monitored for electrolyte derangements regularly, before blood transfusions and while fasting, and iron status estimations were calculated. Changes to the patients’ iron chelation therapy were recorded. Renal function parameters were within normal range for all patients. Hypercalciuria was present in 28% of patients and was significantly negatively correlated with 10-year mean serum ferritin and total transfused iron. Serum levels of uNAG, a marker of tubular endothelial injury, were significantly positively related to the 10-year-amount of transfused iron (r=0.7,p=0.02) in patients with DFO+/-DFP, and were also significantly more prevalent in patients receiving DFX. These study results may have implications for the roles of iron toxicity and iron chelators in B-thalassemia major patients with renal tubular injury.

Severity of functional mitral regurgitation on admission for acute decompensated heart failure predicts long-term risk of rehospitalization and death

1. The rate of all-cause mortality in acute decompensated heart failure 1 year after admission was 4.5 times higher in patients with moderate/severe functional mitral regurgitation than those without it.

2. Rates of 6-month hospitalizations were 2.5 times higher in patients with moderate/severe FMR than those without it.

Evidence Rating Level: 2 (Good)

Functional mitral regurgitation is common in chronic heart failure. It has been linked to reduced mortality and hospitalizations with the use of percutaneous transcatheter repair techniques. In acute decompensated heart failure (ADHF), functional mitral regurgitation (FMR) has been hypothesized to represent a mismatch between ventricular preload and afterload for which pharmacologic treatment is available. To date, its prognostic significance has not been recognized. This retrospective cohort study collected clinical and laboratory data of 2303 adult inpatients with ADHF and left ventricular systolic dysfunction (<50%) to assess the prevalence of FMR and its prognostic significance. Exclusion criteria included no trans-thoracic echocardiogram in the initial 72 hours of admission, normal left ventricular ejection fraction and mitral valve degeneration or ischemic mitral regurgitation. Study groups were formed according to echocardiogram results: none/mild (n=1093, 47%), moderate (n=757, 33%), and moderate/severe FMR (n=453, 20%). Primary outcomes of the study were 1-year post-discharge all-cause mortality, while secondary outcomes were heart failure hospitalization rates. Results showed that more severe FMR was linked with larger left ventricular chamber sizes (diameter at end-diastole 6.1 cm versus 5.9 cm versus 5.7 cm, p<0.001, diameter at end-systole 5.2 cm versus 5 cm versus 4.7 cm, p<0.001) and lower LVEF (25% versus 25% versus 30%, p<0.001). Relative risk for all-cause mortality in the first year after admission was higher in patients with moderate/severe FMR compared with none/mild FMR (HR 1.45, 95% CI, 1.001-2.08, p-0.049). Additionally, rates of 6-month hospitalizations were higher in moderate FMR than those with no or mild FMR (HR 1.24, 95% CI, 1.03-1.49, p=0.02) and similarly higher in those with moderate/severe FMR than those with none or mild FMR (HR 1.25, 95% CI, 1.006-1.55, p=0.043). To improve post-discharge outcomes, prompt characterization, medical optimization and close follow up of acute heart failure patients with FMR should be considered.

Image: PD

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