What is the potential for overdiagnosis of heparin‐induced thrombocytopenia?

Heparin-induced thrombocytopenia (HIT) is caused by platelet-activating antibodies that recognize platelet factor 4//heparin (PF4/H) complexes. According to the "iceberg model," only a subset of anti-PF4/heparin antibodies of IgG class evincing strong platelet-activating properties cause clinical HIT. Since many centers rely predominantly on an anti-PF4/polyanion enzyme-immunoassay (EIA) to diagnose HIT, we estimated the potential for overdiagnosis when only this single test is available. We examined a database of 100 patients in whom the probability of HIT had been estimated using a clinical scoring system (4Ts), and where patients underwent systematic testing for HIT antibodies using three assays: the platelet serotonin release assay (SRA), an "in-house" EIA that detects IgG anti-PF4/heparin antibodies (EIA-IgG), and a commercial EIA that detects anti-PF4/polyanion antibodies of all three immunoglobulin classes (EIA-GTI). Whereas 16 of 100 patients fulfilled a "classic" definition of HIT (intermediate/high probability plus strong platelet-activating anti-PF4/heparin IgG antibodies), an additional 16 patients fulfilled a "liberal" definition in which any investigated patient (irrespective of the pretest probability) who had a positive EIA-GTI was considered to have HIT. The clinical features of these 16 additional patients--including generally weak antibodies and low risk for thrombosis--suggest underlying non-HIT explanations for thrombocytopenia. Patients with a positive SRA generally corresponded to those with intermediate or high pretest probability of HIT who also had strong EIA-GTI reactivity (>1.20 OD units). We conclude there is the potential to overdiagnose HIT by approximately 100% if any positive EIA is considered to "confirm" the diagnosis of HIT irrespective of the clinical scenario.     

One drug or two? Step‐down therapy after i.v. antibiotics for community‐acquired pneumonia

Background: The aim of the study was to describe the oral antibiotics prescribed as step‐down therapy for patients hospitalized for community‐acquired pneumonia (CAP). Methods: A comparative audit of patient records in a Sydney teaching hospital, a district referral hospital and a regional hospital was carried out. Patients older than 15 years admitted between 1 July 2004 and 31 December 2004 with a diagnosis of CAP were identified by diagnostic code. The medical records were reviewed for patient demographics, the specialty of the attending physician, comorbidities, adverse drug events, relevant microbiological results and the antibiotic therapy prescribed for the treatment of pneumonia. Cases were randomly selected from all pneumonia admissions, with approximately equal numbers from urban and regional hospitals. One hundred and ninety‐six admissions for CAP (in 193 patients) were included in this review. Patients were predominantly cared for by respiratory physicians (62%) and geriatricians (14%). Eighty‐nine per cent of patients received dual antibiotic therapy on admission. Results: For patients commenced on two antibiotics, 62% were prescribed two oral antibiotics after completing i.v. therapy, 27% were prescribed one oral agent and 11% were prescribed no step‐down therapy. Geographic location and the presence of a documented antibiotic allergy affected prescribing practice. Neither the specialty of the attending medical officer nor the identification of a likely pathogen affected prescribing practice. Conclusion: Although most of the patients with CAP were initially prescribed two antibiotics, there was considerable variability in whether one, two or no oral agents were prescribed as step‐down therapy.     

Inhibition of Acyl‐CoA Cholesterol Acyltransferase by F12511 (Eflucimibe): Could it be a New Antiatherosclerotic Therapeutic?

Lipid-lowering strategies, particularly with statins, have been extremely useful in the prevention of cardiovascular disease. However, many patients who receive statin monotherapy do not achieve the desired cardiovascular benefits. Accumulation of cholesteryl esters within macrophages constitutes the hallmark of foam cells during atherogenesis. The action of acyl-coenzyme A (CoA): cholesterol acyltransferase (ACAT) leads to formation of cholesterol esters. There are two different ACAT isoforms: ACAT1 and ACAT2. A considerable interest to develop ACAT inhibitors has been emerging. This review has been focused on the current knowledge about a new ACAT inhibitor, F12511 or eflucimibe, and more particularly on its antiatherosclerotic properties.     

Horses for courses? Assessing the potential value of a surrogate,point‐of‐care test for SARS‐CoV‐2 epidemic control

Point‐of‐care tests (POCTs) offer considerable potential for improving clinical and public health management of COVID‐19 by providing timely information to guide decision‐making, but data on real‐world performance are in short supply. Besides SARS‐CoV‐2‐specific tests, there is growing interest in the role of surrogate (non‐specific) tests such as FebriDx, a biochemical POCT which can be used to distinguish viral from bacterial infection in patients with influenza‐like illnesses. This short report assesses what is currently known about FebriDx performance across settings and populations by comparison with some of the more intensively evaluated SARS‐CoV‐2‐specific POCTs. While FebriDx shows some potential in supporting triage for early‐stage infection in acute care settings, this is dependent on SARS‐CoV‐2 being the most likely cause for influenza‐like illnesses, with reduction in discriminatory power when COVID‐19 case numbers are low, and when co‐circulating viral respiratory infections become more prevalent during the autumn and winter. Too little is currently known about its performance in primary care and the community to support use in these contexts, and further evaluation is needed. Reliable SARS CoV2‐specific POCTs—when they become available—are likely to rapidly overtake surrogates as the preferred option given the greater specificity they provide.