Transfusion-associated circulatory overload prevention: a retrospective observational study of diuretic use.

BACKGROUND AND OBJECTIVES: Approaches to preventing transfusion-associated circulatory overload (TACO) include the use of diuretics. The purpose of this study was to determine how commonly diuretics are prescribed in patients receiving a red-blood-cell (RBC) transfusion. MATERIALS AND METHODS: This was a retrospective study of 200 adult inpatient RBC transfusion orders, 50 consecutive at each of four academic institutions. Only the first transfusion order for each patient was included. Only 1 or 2 unit orders were included. The primary outcome was the percentage of patients receiving furosemide peri-transfusion. Secondary objectives included the dose, route, and timing of furosemide and the association of clinical factors with ordering furosemide. RESULTS: The median age was 62·5 years (IQR 53, 73), and 52% were female. Peri-transfusion furosemide was ordered in 16% (95% CI 11-21%). The most common dose was 20 mg (55%), the route intravenous (90%) and timing post-transfusion (74%). At least one risk factor for TACO was present in 55% of patients: renal dysfunction (33%), older than 70 years (28%), history of congestive heart failure (18%), ejection fraction <60% (16%) and diastolic dysfunction (5%). Low haemoglobin as an indication for transfusion (OR 4·2; 95% CI 1·4-12·8) and diuretics on admission (OR 3·5; 95% CI 1·5-8·0) were associated with ordering furosemide peri-transfusion. CONCLUSIONS: Furosemide is not routinely ordered for RBC transfusion, even in patients with risk factors for TACO. Studies assessing the safety, efficacy, optimal dose, and timing of furosemide in preventing TACO are justified.

Audit of appropriate use of platelet transfusions: validation of adjudication criteria.

BACKGROUND AND OBJECTIVES: Platelet (PLT) transfusions must be used appropriately, as they are in chronic short supply, costly and risky to patients. The goals of this audit were to: (1) validate preset adjudication criteria through an audit of appropriateness at four large academic hospitals; (2) identify variability in appropriateness across medical services, physician specialties or hospital locations; and (3) inform logistical or educational interventions that may reduce inappropriate use. MATERIALS AND METHODS: A chart review of two hundred patients receiving PLT transfusions was performed. Fifty consecutive transfusion episodes per site were audited in detail. Each transfusion episode was independently adjudicated as appropriate or inappropriate by two transfusion specialists based on predetermined criteria. RESULTS: The adjudication criteria performed well with simple agreement of 95% (kappa statistic 0·83) between reviewers. Overall, 78% (95% CI: 72-84%) of PLT transfusions were adjudicated as appropriate, with results varying significantly by hospital site (range 62-94%). Prophylactic transfusions for non-bleeding patients had the highest proportion of appropriateness (85%, n = 80), and therapeutic transfusions for bleeding patients had the lowest (73%, n = 99). The lowest levels of appropriate platelet transfusions were observed in the operating rooms (60%) and when ordered by the general surgery service (55%). CONCLUSIONS: One in five platelet transfusions may be unnecessary, suggesting that interventions to improve PLT transfusion practice are warranted.

A novel method for the isolation of extracellular vesicles and RNA from urine.

The discovery of urinary extracellular biomarkers has been impeded by the lack of efficient methods for the isolation of extracellular vesicles (EVs: exosomes and microvesicles) and extracellular nucleic acid (RNA and DNA) from urine. Ultracentrifugation (UC), considered the gold standard for vesicle isolation from many biofluids, is efficacious but laborious, and, like most commercially available methods, is unable to isolate enough material from small volumes for protein or RNA-based biomarker discovery. We have developed a novel precipitation method for the isolation of EVs and nucleic acids from urine. The method, which is now commercially available, takes less than 30 min and does not require polyethylene glycol. Transmission electron microscopy and Nanosight particle analysis confirm that the method isolates intact vesicles with a similar size, shape, and number to UC. Immunoblot analysis of preparations made from a variety of urine samples demonstrates that the method isolates multiple vesicle protein markers more efficiently than other commercial kits, especially from more diluted samples. Bioanalyzer, quantitative reverse transcription polymerase chain reaction, and array analysis show that the method is extremely efficient at the isolation of extracellular miRNAs. The Ymir Genomics EV and Extracellular RNA Isolation Kits offer an efficient and rapid alternative to UC and other commercial kits.

The association of fever with transfusion-associated circulatory overload.

BACKGROUND: Fever is described in transfusion-associated circulatory overload (TACO), reflecting either comprehensive haemovigilance or an inflammatory pathobiology (such as congestion-associated atheroma disruptions). METHODS: Hospital haemovigilance data (1/1/2010-31/12/2012) were reviewed for TACO cases (frequency and mode of referral). TACO with or without fever (TACO+F/-F) was examined for its association with patient age (as a surrogate for atheroma burden) and product age (as a surrogate for storage-related pyrogens). Fever in allergic transfusion reactions was also compared. RESULTS: Of 972 reactions, 107 suspected cases of TACO (11%) were seen. TACO+F vs. TACO-F occurred in 42·1 vs. 57·9%, respectively. TACO+F cases were discovered in referrals to investigate either a fever (in 47·1%) or dyspnoea (in 52·9%). Among TACO+F cases, 24·4% had already been febrile, whereas 75·6% exhibited a new reaction-associated fever. After excluding preexisting fevers, TACO+F occurred in 31·8% of TACO, compared with 8·2% of allergic reactions with fever, for an odds ratio of 5·2 (2·9-9·4 [95% CI]), P < 0·001. TACO+F/TACO-F showed no difference in median host age (69 vs. 64 years, P = 0·3), RBC age (22 days +F/-F, P = 0·9) or severity. CONCLUSION: Transfusion-associated circulatory overload disproportionately exhibits fever compared with allergic reactions. However, TACO+F did not associate with patient or product age, nor reflect severity. To better understand TACO+F, the fever-congestion sequence merits attention. Further study is needed to see whether TACO+F occurs as reproducibly elsewhere, and in association with atherosclerosis in a better characterized cohort.

Human albumin eye drops as a therapeutic option for the management of keratoconjunctivitis sicca secondary to chronic graft-versus-host disease after stem-cell allografting.

BACKGROUND: Keratoconjunctivitis sicca from chronic graft-versus-host disease (cgvhd) after allogeneic stem cell transplantation is common, leading to severe corneal damage and blindness if not treated. We retrospectively examined the efficacy and safety of pooled human albumin eye drops (haeds) for symptom relief in 40 stem-cell transplantation patients after other alternatives had failed. METHODS: The Common Terminology Criteria for Adverse Events (version 4.0) and the cgvhd grading scale were used to compare response in the patients during January 2000 and July 2013. In addition, on days 1 and 30, the haeds were subjected to quality assurance testing for sterility, oncotic pressure, albumin measurement, viscosity, pH, and purity by protein electrophoresis. RESULTS: Use of haeds resulted in symptom relief for 37 patients (92.5%); 3 patients (7.5%) failed to improve with use of haeds (p ≤ 0.0001). Of the 37 patients having symptom relief, 7 (19%) improved from grade 3 to no dry eye symptoms. Proportionately, post-treatment symptom improvement by two grade levels, from 3 to 1 (70%), was significantly higher than improvement by one grade level, from 3 to 2 (11%) or from 2 to 1 (19%, p ≤ 0.0001). Time to symptom relief ranged from 2 weeks to 28 weeks. Of the 40 patients, 38 (95%) had no adverse reactions. Days 1 and 30 quality assurance testing results were equivalent. CONCLUSIONS: Complications of keratoconjunctivitis sicca were well managed and well tolerated with haeds when other remedies failed. Quality assurance testing confirmed that haeds were safe and stable in extreme conditions.

Quantification of myocardial iron deposition by two-dimensional speckle tracking in patients with ß-thalassaemia major and Blackfan-Diamond anaemia.

BACKGROUND: Cardiac disease related to transfusional iron overload is the leading cause of death in patients with ß-thalassaemia major. Early myocardial iron deposition predates decreased left ventricular dysfunction and currently is best assessed by cardiac magnetic resonance. METHODS: Echocardiographic speckle tracking-derived myocardial mechanics were compared with cardiac MRI T2 star (T2*) calculations in 45 chronically transfused patients with ß-thalassaemia major or Diamond-Blackfan anaemia (26 retrospectively and an additional 19 for validation). Two groups were studied: patients with presumed cardiac iron overload and interventricular T2* value ≤20 ms (low T2*) and patients with >20 ms (normal T2*). They were compared with a normal control group of 18 age- and gender-matched patients. RESULTS: Patients with low T2* had a uniform decrease in longitudinal and circumferential strain compared with normal controls (-16±3% vs -20±3% and -20±4% vs -23±5%, respectively; p<0.0005). Peak twist and peak apical rotation were lower in patients with low T2* than in those with normal T2* or normal control patients. Conversely, no significant difference was observed between patients with normal T2* and controls. There was a strong and direct logarithmic correlation between average global longitudinal strain and T2* values (r=-0.68, p=0.0007). Using a cut-off of ≤-17%, global longitudinal strain predicted a T2* value of <20 ms with a sensitivity of 76% and a specificity of 88%. CONCLUSION: Myocardial mechanics offers a simple alternative to cardiac MRI for assessing significant myocardial iron deposition.

Changes in intravenous immunoglobulin prescribing patterns during a period of severe product shortages, 1995-2000.

BACKGROUND AND OBJECTIVES: Canadian consumption of intravenous immunoglobulin (IVIG) has increased dramatically since it was first marketed in the early 1980s, and Canada is now the world's largest per capita consumer. During the late 1990s, worldwide product shortages of IVIG occurred. This study was designed to identify the disease conditions for which IVIG was being prescribed in academic hospitals during this period, and to explore the effects that IVIG shortages had on prescribing patterns. MATERIALS AND METHODS: Blood bank and pharmacy records of IVIG distribution were collected retrospectively from four Toronto teaching hospitals for the period 1995-2000. These records were then cross-referenced with patient medical records to determine the indication for IVIG administration. RESULTS: A total of 100,208 g of IVIG was prescribed to 429 patients over a 6-year period. Most of the IVIG consumption was in patients with haematological (22%) or neurological (20%) conditions, in recipients of bone marrow transplants (19%) and in patients with infectious disease-related conditions (including congenital and acquired hypogammoglobulinaemia, 18%). Dermatological conditions (7%) were the most rapidly growing indication for IVIG usage during the 6-year period of review, increasing from 0% of annual IVIG usage in 1995 to 16% in 2000. Over 80% of the diseases treated were supported by published recommendations. After 1997 there was an abrupt decline in the annual number of patients treated, primarily owing to a decline in single-use recipients. Annual consumption of IVIG, however, remained stable. CONCLUSIONS: IVIG shortages were followed by a decrease in the number of single-use recipients, who probably represented empirical use of IVIG; this had little effect on the total amount of IVIG distributed annually. Stricter adherence to currently available published recommendations may not be the optimal means of controlling IVIG use within an academic hospital setting. Rather, emphasis may be better placed on improving the evidence base upon which these recommendations are made, for example by conducting controlled prospective clinical trials.

How Nova Scotia general practitioners choose antibiotics for the empirical treatment of community-acquired pneumonia.

OBJECTIVE: To gain an understanding of how physicians in general practice choose antibiotics for the empirical treatment of community-acquired pneumonia (CAP). DESIGN: Questionnaire with three sample cases of CAP and a knowledge assessment (mailed to half of the physicians). POPULATION STUDIED: Nova Scotia family physicians. RESULTS: One hundred and eighty-four of the 841 (21.9%) physicians who were mailed a questionnaire responded. A knowledge assessment showed satisfactory knowledge except in two areas - an overestimation of the prevalence of penicillin-resistant Streptococcus pneumoniae in Nova Scotia and the view that ciprofloxacin was an effective antibiotic for the treatment of CAP (42% of physicians). As the complexity of the case increased, there was decreasing consensus regarding the choice of antibiotic therapy and a decline in prescribing according to guidelines for the treatment of CAP. Also, as the complexity of the cases increased, it became increasingly difficult to discern a decision-making strategy. For the simplest case - a 17-year-old male with presumed Mycoplasma pneumoniae pneumonia - physician factors (age, family practice training), desire to target specific pathogens, and concern with resistance and side effects affected the choice of antibiotic. However, for the most complex case - a 45-year-old female with severe pneumonia - familiarity with such a case was the only significant factor and led to treatment with a combination of antibiotics designed to treat both typical and atypical pathogens. CONCLUSIONS: For uncomplicated cases of CAP, physician factors, desire to treat specific pathogens and concern with resistance affect the choice of antibiotic therapy. For complex cases, familiarity with such cases was the only factor that influenced choice of antibiotic therapy.

Reasons for choice of antibiotic for the empirical treatment of CAP by Canadian infectious disease physicians.

BACKGROUND: Previous studies have documented substantial variation in physician prescribing practices for the treatment of community-acquired pneumonia. Much of this variation is the result of empirical treatment, in which physicians must choose antibiotics in the a8bsence of culture and sensitivity data. OBJECTIVE: To explore the factors that influence antibiotic choice for the empirical treatment of community-acquired pneumonia. MATERIALS AND METHODS: Case-based questionnaires were mailed to all 157 members of the Canadian Infectious Disease Society in June 1996. The questionnaires presented three clinical cases and asked respondents which antibiotics they would most likely prescribe. Half the questionnaires were closed-ended, and half were open-ended. In the former, respondents were asked to explain their antibiotic choice by assigning weights to a list of clinical factors. In the latter, respondents were asked to explain their antibiotic choice by providing a short written answer. Respondents were grouped by the class of antibiotics they selected. These groups were then compared with regards to respondent characteristics (age, years of infectious disease experience, adult versus pediatric practice, country of training, province of practice) and rationale for the treatment chosen. Rationale for drug choice was analyzed statistically for the closed-ended questionnaires and qualitatively for the open-ended questionnaires. RESULTS: A response rate of 84.6% was obtained. For the first clinical case, in which the patient was young and had no underlying illness, the majority of respondents chose a macrolide (74.7%). In the second case, in which the patient was older and had evidence of comorbidity, the most common choice of antibiotic was a penicillin (40.8%). In the third case, in which the patient had intensive care unit-requiring pneumonia, the most popular choice was combination therapy of a third-generation cephalosporin and a macrolide (43.2%). There was decreasing consensus regarding the choice of antibiotics as the complexity of the cases increased. There was evidence that prescribing variation could occasionally be attributed to both respondent characteristics and the use of different decision-making strategies. CONCLUSIONS: Despite the relative homogeneity of the physicians studied, considerable variation in antibiotic choice was observed. In the first case, this variation was based on the issue of whether the patient had a typical or atypical infection. In the second case, the choice of antibiotic was related to the issue of infection by Haemophilus influenzae, although the results of the Gram stain suggested a pneumococcal infection. In the third case, variance appeared to be based more on the respondent's age and province of practice than on any difference in decision-making strategy.