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1.  Comparing influenza vaccine efficacy against mismatched and matched strains: a systematic review and meta-analysis 
BMC Medicine  2013;11:153.
Influenza vaccines are most effective when the antigens in the vaccine match those of circulating strains. However, antigens contained in the vaccines do not always match circulating strains. In the present work we aimed to examine the vaccine efficacy (VE) afforded by influenza vaccines when they are not well matched to circulating strains.
We identified randomized clinical trials (RCTs) through MEDLINE, EMBASE, the Cochrane Library, and references of included RCTs. RCTs reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of matching and non-matching influenza strains were included. Two independent reviewers screened citations/full-text articles, abstracted data, and appraised risk of bias. Conflicts were resolved by discussion. A random effects meta-analysis was conducted. VE was calculated using the following formula: (1 - relative risk × 100%).
We included 34 RCTs, providing data on 47 influenza seasons and 94,821 participants. The live-attenuated influenza vaccine (LAIV) showed significant protection against mismatched (six RCTs, VE 54%, 95% confidence interval (CI) 28% to 71%) and matched (seven RCTs, VE 83%, 95% CI 75% to 88%) influenza strains among children aged 6 to 36 months. Differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 75%, 95% CI 41% to 90%) and mismatched influenza B (five RCTs, VE 42%, 95% CI 22% to 56%) estimates among children aged 6 to 36 months. The trivalent inactivated vaccine (TIV) also afforded significant protection against mismatched (nine RCTs, VE 52%, 95% CI 37% to 63%) and matched (eight RCTs, VE 65%, 95% CI 54% to 73%) influenza strains among adults. Numerical differences were observed between the point estimates for mismatched influenza A (five RCTs, VE 64%, 95% CI 23% to 82%) and mismatched influenza B (eight RCTs, VE 52%, 95% CI 19% to 72%) estimates among adults. Statistical heterogeneity was low (I2 <50%) across all meta-analyses, except for the LAIV meta-analyses among children (I2 = 79%).
The TIV and LAIV vaccines can provide cross protection against non-matching circulating strains. The point estimates for VE were different for matching versus non-matching strains, with overlapping CIs.
PMCID: PMC3706345  PMID: 23800265
Antigenic variation; Cross protection; Influenza A virus; Influenza B virus; Meta-analysis; Systematic review; Vaccines
2.  Effect of influenza vaccines against mismatched strains: a systematic review protocol 
Systematic Reviews  2012;1:35.
Influenza vaccines are most effective when the antigens in the vaccine match those of circulating influenza strains. The extent to which the vaccine is protective when circulating strains differ from vaccine antigens, or are mismatched, is uncertain. We propose to systematically review the cross-protection offered by influenza vaccines against circulating influenza A or B viruses that are not antigenically well-matched to vaccine strains.
This is a protocol for a systematic review and meta-analysis. Placebo-controlled randomized clinical trials (RCTs) reporting laboratory-confirmed influenza among healthy participants vaccinated with antigens of influenza strains that differed from those circulating will be included. The primary outcome is the incidence of laboratory-confirmed influenza (polymerase chain reaction (PCR) or viral culture). The secondary outcome is the incidence of laboratory-confirmed influenza through antibody assay (a less sensitive test than PCR or viral culture) alone or combined with PCR, and/ or viral culture. The review will be limited to RCTs written in English.
We will search MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, previous influenza reviews, and the reference lists of included studies to identify potentially relevant RCTs. Two independent reviewers will conduct all levels of screening, data abstraction, and quality appraisal (using the Cochrane risk of bias tool).
If appropriate, random effects meta-analysis of vaccine efficacy will be conducted in SAS (version 9.2) by calculating the relative risk. Vaccine efficacy will be calculated using the following formula: (1 - relative risk × 100). The results will be analyzed by type of vaccine (live attenuated, trivalent inactivated, or other). Subgroup analysis will include the effects of age (children, adults, older participants), and influenza A versus influenza B on the results. For influenza B we will also consider variable degrees of antigenic mismatch (lineage and drift mismatch).
Our results can be used by researchers and policy-makers to help predict the efficacy of influenza vaccines during mismatched influenza seasons. Furthermore, the review will be of interest to patients and clinicians to determine whether to get immunized or support immunization for a particular influenza season.
PMCID: PMC3488466  PMID: 22846340
Antigenic variation; Cross protection; Influenza A virus; Influenza B virus; Protocol; Systematic review; Vaccines
3.  Errors Associated with IV Infusions in Critical Care 
All medication errors are serious, but those associated with the IV route of administration often result in the most severe outcomes. According to the literature, IV medications are associated with 54% of potential adverse events, and 56% of medication errors.
To determine the type and frequency of errors associated with prescribing, documenting, and administering IV infusions, and to also determine if a correlation exists between the incidence of errors and either the time of day (day versus night) or the day of the week (weekday versus weekend) in an academic medicosurgical intensive care unit without computerized order entry or documentation.
As part of a quality improvement initiative, a prospective, observational audit was conducted for all IV infusions administered to critically ill patients during 40 randomly selected shifts over a 7-month period in 2007. For each IV infusion, data were collected from 3 sources: direct observation of administration of the medication to the patient, the medication administration record, and the patient’s medical chart. The primary outcome was the occurrence of any infusion-related errors, defined as any errors of omission or commission in the context of IV medication therapy that harmed or could have harmed the patient.
It was determined that up to 21 separate errors might occur in association with a single dose of an IV medication. In total, 1882 IV infusions were evaluated, and 5641 errors were identified. Omissions or discrepancies related to documentation accounted for 92.7% of all errors. The most common errors identified via each of the 3 data sources were incomplete labelling of IV tubing (1779 or 31.5% of all errors), omission of infusion diluent from the medication administration record (474 or 8.4% of all errors), and discrepancy between the medication order as recorded in the patient’s chart and the IV medication that was being infused (105 or 1.9% of all errors).
Strict definitions of errors and direct observation methods allowed identification of errors at every step of the medication administration process that was evaluated. Documentation discrepancies were the most prevalent type of errors in this paper-based system.
PMCID: PMC3282194  PMID: 22479108
IV infusion; continuous infusion; errors; intensive care unit; critical care; perfusion i.v.; perfusion continue; erreurs; unité de soins intensifs; soins aux malades en phase critique
4.  Survey of information technology in Intensive Care Units in Ontario, Canada 
The Intensive Care Unit (ICU) is a data-rich environment where information technology (IT) may enhance patient care. We surveyed ICUs in the province of Ontario, Canada, to determine the availability, implementation and variability of information systems.
A self-administered internet-based survey was completed by ICU directors between May and October 2006. We measured the spectrum of ICU clinical data accessible electronically, the availability of decision support tools, the availability of electronic imaging systems for radiology, the use of electronic order entry and medication administration systems, and the availability of hardware and wireless or mobile systems. We used Fisher's Exact tests to compare IT availability and Classification and Regression Trees (CART) to estimate the optimal cut-point for the number of computers per ICU bed.
We obtained responses from 50 hospitals (68.5% of institutions with level 3 ICUs), of which 21 (42%) were university-affiliated. The majority electronically accessed laboratory data and imaging reports (92%) and used picture archiving and communication systems (PACS) (76%). Other computing functions were less prevalent (medication administration records 46%, physician or nursing notes 26%; medication order entry 22%). No association was noted between IT availability and ICU size or university affiliation. Sites used clinical information systems from15 different vendors and 8 different PACS systems were in use. Half of the respondents described the number of computers available as insufficient. Wireless networks and mobile computing systems were used in 23 ICUs (46%).
Ontario ICUs demontrate a high prevalence of the use of basic information technology systems. However, implementation of the more complex and potentially more beneficial applications is low. The wide variation in vendors utilized may impair information exchange, interoperability and uniform data collection.
PMCID: PMC2233621  PMID: 18218117
5.  Prospective evaluation of an internet-linked handheld computer critical care knowledge access system 
Critical Care  2004;8(6):R414-R421.
Critical care physicians may benefit from immediate access to medical reference material. We evaluated the feasibility and potential benefits of a handheld computer based knowledge access system linking a central academic intensive care unit (ICU) to multiple community-based ICUs.
Four community hospital ICUs with 17 physicians participated in this prospective interventional study. Following training in the use of an internet-linked, updateable handheld computer knowledge access system, the physicians used the handheld devices in their clinical environment for a 12-month intervention period. Feasibility of the system was evaluated by tracking use of the handheld computer and by conducting surveys and focus group discussions. Before and after the intervention period, participants underwent simulated patient care scenarios designed to evaluate the information sources they accessed, as well as the speed and quality of their decision making. Participants generated admission orders during each scenario, which were scored by blinded evaluators.
Ten physicians (59%) used the system regularly, predominantly for nonmedical applications (median 32.8/month, interquartile range [IQR] 28.3–126.8), with medical software accessed less often (median 9/month, IQR 3.7–13.7). Eight out of 13 physicians (62%) who completed the final scenarios chose to use the handheld computer for information access. The median time to access information on the handheld handheld computer was 19 s (IQR 15–40 s). This group exhibited a significant improvement in admission order score as compared with those who used other resources (P = 0.018). Benefits and barriers to use of this technology were identified.
An updateable handheld computer system is feasible as a means of point-of-care access to medical reference material and may improve clinical decision making. However, during the study, acceptance of the system was variable. Improved training and new technology may overcome some of the barriers we identified.
PMCID: PMC1065064  PMID: 15566586
clinical; computer; critical care; decision support systems; handheld; internet; point-of-care systems; practice guidelines; simulation
6.  Practising evidence-based medicine: the design and implementation of a multidisciplinary team-driven extubation protocol 
Critical Care  2001;5(6):349-354.
Evidence from recent literature shows that protocol-directed extubation is a useful approach to liberate patients from mechanical ventilation (MV). However, research evidence does not necessarily provide guidance on how to implement changes in individual intensive care units (ICUs). We conducted the present study to determine whether such an evidence-based strategy can be implemented safely and effectively using a multidisciplinary team (MDT) approach.
We designed a MDT-driven extubation protocol. Multiple meetings were held to encourage constructive criticism of the design by attending physicians, nurses and respiratory care practitioners (RCPs), in order to define a protocol that was evidence based and acceptable to all clinical staff involved in the process of extubation. It was subsequently implemented and evaluated in our medical/ surgical ICU. Outcomes included response of the MDT to the initiative, duration of MV and stay in the ICU, as well as reintubation rate.
The MDT responded favourably to the design and implementation of this MDT-driven extubation protocol, because it provided greater autonomy to the staff. Outcomes reported in the literature and in the historical control group were compared with those in the protocol group, and indicated similar durations of MV and ICU stay, as well as reintubation rates. No adverse events were documented.
An MDT approach to protocol-directed extubation can be implemented safely and effectively in a multidisciplinary ICU. Such an effort is viewed favourably by the entire team and is useful in enhancing team building.
PMCID: PMC83857  PMID: 11737924
extubation protocol; mechanical ventilation; multidisciplinary team; spontaneous breathing trial; weaning
7.  Synthesis of Hemoglobin AIc and Related Minor Hemoglobins by Erythrocytes 
Factors that influence hemoglobin (Hb)AIc synthesis by intact erythrocytes were studied in vitro. After incubation cells were lysed, and hemoglobins were separated by isoelectric focusing on polyacrylamide slab gels and quantitated by microdensitometry. HbAIc increased with time, glucose concentrations (5-500 mM), and incubation temperature (4°-37°C). Low temperatures allowed prolonged incubations with minimal hemolysis. At 4°C HbAIc increased linearly with time for 6 wk; after incubation at the highest glucose concentration, HbAIc comprised 50% of total hemoglobin.
Insulin (1 and 0.1 mU/ml) did not affect HbAIc synthesis in vitro. In addition to glucose, galactose and mannose, but not fructose, served as precursors to HbAIc. A good substrate for hexokinase (2-deoxyglucose) and a poor hexokinase substrate (3-O-methylglucose), were better precursors for HbAIc synthesis than glucose, suggesting that enzymatic phosphorylation of glucose is not required for HbAIc synthesis. Autoradiography after erythrocyte incubation with 32P-phosphate showed incorporation of radioactivity into HbAIa1 and AIa2, but not HbAIb, AIc, or A. Acetylated HbA, generated during incubation with acetylsalicylate, migrated anodal to HbAIc and clearly separated from it.
Erythrocytes from patients with insulinopenic diabetes mellitus synthesized HbAIc at the same rate as controls when incubated with identical glucose concentrations. Likewise, the rate of HbAIc synthesis by erythrocytes from patients with cystic fibrosis and congenital spherocytosis paralleled controls. When erythrocytes from cord blood and from HbC and sickle cell anemia patients were incubated with elevated concentrations of glucose, fetal Hb, HbC, and sickle Hb decreased, whereas hemoglobins focusing at isoelectric points near those expected for the corresponding glycosylated derivatives appeared in proportionately increased amounts.
PMCID: PMC372088  PMID: 36412

Results 1-7 (7)