Biomedical subjects

Dean Fergusson

Publications and source records attributed to Dean Fergusson.

At least 19 recordsLinked to original sources

PubMed2006

Conversion from calcineurin inhibitors to sirolimus for chronic renal allograft dysfunction: a systematic review of the evidence.

BACKGROUND: Conversion from a calcineurin inhibitor to sirolimus has been used as a strategy to improve deteriorating renal allograft function but the efficacy and safety of this intervention is unknown. METHODS: We performed a systematic review of studies that involved conversion from a calcineurin inhibitor to sirolimus in kidney transplantation. The search yielded five randomized trials (n=1,040 patients) and 25 nonrandomized studies (n=977 patients). RESULTS: In the randomized trials, conversion to sirolimus improved short-term creatinine clearance (weighted mean difference 6.4 mL/min; 95% CI 1.9 to 11.0) compared to controls. In the nonrandomized studies, renal function improved or stabilized in 66% (95% CI 61% to 72%), creatinine clearance improved (weighted mean change 5.7 mL/min; 95% CI 1.4 to 10.1), cholesterol increased (weighted mean change 20.8 mg/dL; 95% CI 11.2 to 30.4) and triglycerides increased (weighted mean change 40.1 mg/dL; 95% CI 18.6 to 61.7). Sirolimus was discontinued by 28% of patients (95% CI 0 to 59%) in the randomized trials and 17% (95% CI 12 to 22%) in the nonrandomized trials. CONCLUSION: Conversion to sirolimus is associated with an improvement in short-term renal function. However, given the discontinuation rate and potential side effects, adequately powered randomized trials with longer follow-up of hard outcomes are needed to determine whether this strategy leads to a lasting benefit in the clinical care of transplant recipients.

Calcineurin Inhibitors↗

PubMed2006

The prevalence of antibodies to the platelet factor 4 -heparin complex and association with access thrombosis in patients on chronic hemodialysis.

INTRODUCTION: Heparin-induced thrombocytopenia is a serious complication that can lead to thrombocytopenia, venous and arterial thrombosis. Patients with this disorder develop antibodies to the platelet factor 4-heparin (PF4-H) complex. Hemodialysis patients are repeatedly exposed to heparin and are at risk for developing PF4-H antibodies. We sought to determine the prevalence of PF4-H antibodies in a large cohort of patients on chronic hemodialysis and to evaluate the relationship between PF4-H antibodies and hemodialysis vascular access thrombosis in a case-control study. MATERIAL AND METHODS: Pre-dialysis blood samples were drawn on 419 patients; 107 cases with access thrombosis and 312 controls that never had access thrombosis. All samples were screened for PF4-H antibodies using an ELISA assay (GTI PF4 Enhanced, GTI Diagnostics). All positive and indeterminate samples were then tested using an IgG-specific PF4-H ELISA assay and a platelet serotonin-release assay. RESULTS: Antibodies to PF4-H were positive in 54 (12.9%) patients using the screening ELISA assay. Nine (2.1%) patients had IgG-specific PF4-H antibodies. None of the patient's had a positive platelet serotonin-release assay. No relationship between hemodialysis access thrombosis and PF4-H antibodies was noted using the screening ELISA assay (unadjusted odds ratio 0.63; 95% CI 0.30-1.30; P = 0.21), the IgG-specific ELISA assay (unadjusted odds ratio 0.83; 95% CI 0.17-4.06; P = 0.82) or indeterminate platelet serotonin-release assay results (unadjusted odds ratio 0.97;95% CI 0.10-9.44;P = 0.98). CONCLUSIONS: Hemodialysis with repeated exposure to unfractionated heparin was associated with a moderately elevated prevalence of PF4-H antibodies. However, our results do not support a relationship between PF4-H antibodies and hemodialysis vascular access thrombosis.

Adult↗

PubMed2006

Does this patient have deep vein thrombosis?

CONTEXT: Outpatients with suspected deep vein thrombosis (DVT) have nonspecific signs and symptoms. Missed DVT diagnosis may result in fatal pulmonary embolism. Since many patients may have DVT, a selective and efficient diagnostic process is needed. OBJECTIVE: To systematically review trials that determined the prevalence of DVT using clinical prediction rules either with or without D-dimer, for the diagnosis of DVT. DATA SOURCES: English- and French-language studies were identified from MEDLINE from 1990 to July 2004 and supplemented by a review of all relevant bibliographies. STUDY SELECTION: We included studies that prospectively enrolled consecutive, unselected outpatients with suspected DVT and applied clinical prediction rules before D-dimer testing or diagnostic imaging. All studies included sufficient information to allow the calculation of the prevalence of DVT for at least 1 of the 3 clinical probability estimates (low, moderate, or high). We required that patients be followed up for a minimum 3-month period. Unless the clinical model incorporated prior DVT, studies were excluded if patients with a history of prior DVT were enrolled. DATA EXTRACTION: Two reviewers independently reviewed and abstracted data for estimating the prevalence of DVT, sensitivity, specificity, and likelihood ratios (LRs) of D-dimer in each of the 3 clinical probability estimates. Data for the D-dimer in all studies were pooled and analyzed as high-sensitivity/low-specificity test or a moderate-sensitivity/moderate-specificity test. DATA SYNTHESIS: Fourteen studies involving more than 8000 patients used 1 clinical prediction rule for diagnosing DVT, of which 11 incorporated D-dimer testing in the diagnostic algorithm. The prevalence of DVT in the low, moderate, and high clinical probability groups was 5.0% (95% CI, 4.0%-8.0%), 17% (95% CI, 13%-23%), and 53% (95% CI, 44%-61%), respectively. The overall prevalence of DVT was 19% (95% CI, 16%-23%). Pooling all studies, the sensitivity, specificity, and negative LRs of D-dimer testing in the low probability group were 88% (95% CI, 81%-92%), 72% (95% CI, 65%-78%), and 0.18% (95% CI, 0.12-0.18); in the moderate probability group: 90% (95% CI, 80%-95%), 58% (95% CI, 49%-67%), and 0.19% (95% CI, 0.11-0.32); and in the high probability group: 92% (95% CI, 85%-96%), 45% (95% CI, 37%-52%), and 0.16% (95% CI, 0.09-0.30). The LRs for a normal result on a high or moderately sensitive D-dimer assay among patients with: (1) low clinical suspicion were 0.10 (95% CI, 0.03-0.37) and 0.20 (95% CI, 0.12-0.31); (2) moderate clinical suspicion were 0.05 (95% CI, 0.01-0.21) and 0.23 (95% CI, 0.13-0.39); and (3) high clinical suspicion were 0.07 (95% CI, 0.03-0.18) and 0.15 (95% CI, 0.10-0.38). CONCLUSIONS: Diagnostic accuracy for DVT improves when clinical probability is estimated before diagnostic tests. Patients with low clinical probability on the predictive rule have prevalence of DVT of less than 5%. In low-probability patients with negative D-dimer results, diagnosis of DVT can be excluded without ultrasound; in patients with high clinical suspicion for DVT, results should not affect clinical decisions.

Algorithms↗

PubMed2006

Identification of domains relevant to health-related quality of life in patients undergoing major surgery.

This study examined themes relevant to health-related quality of life as identified by patients undergoing major surgery and by health care providers. Semi-structured interviews were conducted with 52 patients undergoing major abdominal, cardiac, orthopedic, thoracic, or vascular surgical procedures and 33 health professionals from various disciplines. A total of 58 themes were identified by content analysis. These themes were categorized into 6 domains. These were: physical well-being (14 themes), emotional well-being (13 themes), concern about quality of care (12 themes), social well-being (12 themes), cognitive preparation (4 themes), and spiritual well-being (3 themes). In general, we found that most aspects of health-related quality of life were common across various major surgical procedures and between patients and health care providers. However, when we examined the coverage of these themes in seven commonly-used health-related quality of life instruments, we found that many of the most frequently mentioned themes were not assessed with the available measures. A new evaluative instrument tailored to patients undergoing major surgery may therefore be warranted.

Aged↗

PubMed2006

Clinical consequences of red cell storage in the critically ill.

Red cell (RBC) transfusions are a potentially life-saving therapy employed during the care of many critically ill patients to replace losses in hemoglobin to maintain oxygen delivery to vital organs. During storage, RBCs undergo a series of biochemical and biomechanical changes that reduce their survival and function. Additionally, accumulation of other biologic by-products of RBC preservation may be detrimental to recipients of blood transfusions. Laboratory studies and an increasing number of observational studies have raised the possibility that prolonged RBC storage adversely affects clinical outcomes. In this article, the laboratory and animal experiments evaluating changes to RBCs during prolonged storage are reviewed. Subsequently, the clinical studies that have evaluated the clinical consequences of prolonged RBC storage are reviewed. These data suggest a possible detrimental clinical effect associated with the transfusion of stored RBCs; randomized clinical trials further evaluating the clinical consequences of transfusing older stored RBCs are required.

Animals↗

PubMed2006

Effect of study setting on anticoagulation control: a systematic review and metaregression.

BACKGROUND: For patients receiving therapy with oral anticoagulants (OACs), the proportion of time spent in the therapeutic range (ie, anticoagulation control) is strongly associated with bleeding and thromboembolic risk. The effect of study-level factors, especially study setting, on anticoagulation control is unknown. OBJECTIVES: Describe anticoagulation control achieved in the published literature. We also used metaregressive techniques to determine which study-level factors significantly influenced anticoagulation control. STUDIES: All published randomized or cohort studies that measured international normalized ratios (INRs) serially in anticoagulated patients and reported the proportion of time between INRs ranging from 1.8 to 2.0 and 3.0 to 3.5. RESULTS: We identified 67 studies with 123 patient groups having 50,208 patients followed for a total of 57,154.7 patient-years. A total of 68.3% of groups were from anticoagulation clinics, 7.3% were from clinical trials, and 24.4% were from community practices. Overall, patients were therapeutic 63.6% of time (95% confidence interval [CI], 61.6 to 65.6). In the metaregression model, study setting had the greatest effect on anticoagulation control with studies in community practices having significantly lower control than either anticoagulation clinics or clinical trials (-12.2%; 95% CI, -19.5 to -4.8; p < 0.0001). Self-management was associated with a significant improvement of time spent in the therapeutic range (+7.0%; 95% CI, 0.7 to 13.3; p = 0.03). CONCLUSIONS: Patients who have received anticoagulation therapy spend a significant proportion of their time with an INR out of the therapeutic range. Patients from community practices showed significantly worse anticoagulation control than those from anticoagulation clinics or clinical trials. This should be considered when interpreting the results of, and generalizing from, studies involving OACs.

Anticoagulants↗

PubMed2005

Reducing the amount of blood transfused: a systematic review of behavioral interventions to change physicians' transfusion practices.

BACKGROUND: Transfusion services have used various techniques to reduce blood product utilization. Given the potential adverse effects of transfusions and the resources consumed in implementing strategies to reduce transfusions, there is a need to understand their effectiveness. Therefore, we performed a systematic review of the literature to examine the effectiveness of behavioral interventions to reduce blood product utilization. METHODS: We identified all relevant articles through the use of electronic searches of MEDLINE and EMBASE, as well as hand searches of review articles and personal files. The electronic searches included articles published between January 1966 and May 2003. The searches included the terms blood transfusion, plasma exchange, guidelines, education, practice patterns, and professional practice. The outcomes of interest were the number of units transfused and the proportion of patients who received transfusions. RESULTS: Nineteen studies examining the effectiveness of single (guidelines, prospective audits, retrospective audits, and reminders) or multifaceted interventions in reducing red blood cell, platelet, plasma, cryoprecipitate, and albumin transfusions met the inclusion criteria. Eighteen studies demonstrated a relative reduction in the number of units given (range, 9%-77%) or the proportion of patients receiving transfusions (range, 17%-79%). The reported reductions were qualitatively similar for the different blood products studied. No particular intervention or combination of interventions appeared more effective in reducing utilization. CONCLUSIONS: Behavioral interventions, including simple interventions, appear to be effective in changing physician transfusion practices and reducing blood utilization. Appropriately designed clinical trials are still needed to determine the relative effectiveness of different interventions to change practices.

Behavior↗

PubMed2005

Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials.

OBJECTIVE: To establish whether an association exists between use of selective serotonin reuptake inhibitors (SSRIs) and suicide attempts. DESIGN: Systematic review of randomised controlled trials. DATA SOURCES: Medline and the Cochrane Collaboration's register of controlled trials (November 2004) for trials produced by the Cochrane depression, anxiety, and neurosis group. SELECTION OF STUDIES: Studies had to be randomised controlled trials comparing an SSRI with either placebo or an active non-SSRI control. We included clinical trials that evaluated SSRIs for any clinical condition. We excluded abstracts, crossover trials, and all trials whose follow up was less than one week. RESULTS: Seven hundred and two trials met our inclusion criteria. A significant increase in the odds of suicide attempts (odds ratio 2.28, 95% confidence 1.14 to 4.55, number needed to treat to harm 684) was observed for patients receiving SSRIs compared with placebo. An increase in the odds ratio of suicide attempts was also observed in comparing SSRIs with therapeutic interventions other than tricyclic antidepressants (1.94, 1.06 to 3.57, 239). In the pooled analysis of SSRIs versus tricyclic antidepressants, we did not detect a difference in the odds ratio of suicide attempts (0.88, 0.54 to 1.42). DISCUSSION: Our systematic review, which included a total of 87 650 patients, documented an association between suicide attempts and the use of SSRIs. We also observed several major methodological limitations in the published trials. A more accurate estimation of risks of suicide could be garnered from investigators fully disclosing all events.

Adult↗

PubMed2005

Ensuring high accuracy of data abstracted from patient charts: the use of a standardized medical record as a training tool.

BACKGROUND AND OBJECTIVE: The quality and integrity of information is pivotal to the validity and reliability of inferences drawn in research. The aim of this study is to demonstrate that standardized medical records can be used as a data abstraction training tool and a quality control measure to assess the validity of medical record data abstraction. METHODS: Sixteen hospitals participating in a large multicenter study completed standardized data abstraction forms for three representative patient charts, one in each of the clinical areas of postoperative critical care and trauma, cardiac surgery, and repair of hip fracture. The completed forms were then compared to an established gold standard. RESULTS: The mean level of accuracy of the completed data abstraction forms in each of the above three clinical areas were 91.8, 77.5, and 91.5%, respectively. Missing data accounted for 19% of all discrepancies between the abstracted information and the gold standard. If queries and amendments were made by the study's coordinating center, the mean level of accuracy increased to 94.5, 82.5, and 92.9%, respectively. CONCLUSION: The present study stressed the need for quality control measures in abstracting information from medical records to ensure the accuracy and completeness of the data abstracted.

Biomedical Research↗

PubMed2005

Reliability of point-of-care testing for glucose measurement in critically ill adults.

BACKGROUND: Glycemic control is increasingly being recognized as a priority in the treatment of critically ill patients. Titration and monitoring of insulin infusions involve frequent blood glucose measurement to achieve target glucose ranges and prevent adverse events related to hypoglycemia. Therefore, it is imperative that bedside glucose testing methods be safe and accurate. OBJECTIVE: To determine the accuracy and clinical impact of three common methods of bedside point-of-care testing for glucose measurements in critically ill patients receiving insulin infusions. DESIGN: Prospective observational study. SETTING: A 21-bed mixed medical/surgical intensive care unit of a tertiary care teaching hospital. PATIENTS: Thirty consecutive critically ill patients who were vasopressor-dependent (n = 10), had significant peripheral edema (n = 10), or were admitted following major surgery (n = 10). MEASUREMENTS: Findings from three different methods of glucose measurement were compared with central laboratory measurements: (1) glucose meter analysis of capillary blood (fingerstick); (2) glucose meter analysis of arterial blood; and (3) blood gas/chemistry analysis of arterial blood. Patients were enrolled for a maximum of 3 days and had a maximum of nine sets of measurements determined during this time. RESULTS: Clinical agreement with the central laboratory was significantly better with arterial blood analysis (69.9% and 76.5% for glucose meter and blood gas/chemistry analysis, respectively) than with capillary blood analysis (56.8%; p = .039 and .001, respectively). During hypoglycemia, clinical agreement was only 26.3% with capillary blood analysis and 55.6% and 64.9% for glucose meter and blood gas/chemistry analysis of arterial blood (p = .010 and <.001, respectively). Glucose meter analysis of both arterial and capillary blood tended to provide higher glucose values, whereas blood gas/chemistry analysis of arterial blood tended to yield lower glucose values. CONCLUSIONS: The magnitude of the differences in the glucose values offered by the four different methods of glucose measurement led to frequent clinical disagreements regarding insulin dose titration in the context of an insulin infusion protocol for aggressive glucose control.

APACHE↗

PubMed2005

Use of intravenous immunoglobulin for treatment of neurologic conditions: a systematic review.

BACKGROUND: Given the increasing use of intravenous immunoglobulin (IVIG) for various neurologic conditions and uncertainty pertaining to its benefits and harms, a systematic review was conducted of randomized controlled trials (RCTs) evaluating IVIG for all neurologic indications for which there was at least one published trial. STUDY DESIGN AND METHODS: For this systematic review, a systematic search strategy was applied to MEDLINE (1966-June 2003) and the Cochrane Register of Controlled Trials (June 2003) to identify potentially eligible RCTs comparing IVIG to placebo or an active control. All dosage regimens were considered. Abstracts were excluded, and no restriction was placed on language of publication. Two investigators independently performed data extraction with a standardized form. Measures of effect were calculated for each trial independently, and studies were pooled based on clinical and methodologic judgment as to its appropriateness. Where pooling of trials was inappropriate, a qualitative discussion of findings is provided. RESULTS AND CONCLUSIONS: Thirty-seven trials representing 14 conditions were identified. IVIG is more effective than placebo for treatment of relapsing-remitting multiple sclerosis and idiopathic chronic inflammatory demyelinating polyneuropathy. There is also potential benefit for treatment of multifocal motor neuropathy, myasthenia gravis, dermatomyositis, stiff-person syndrome, and Lambert-Eaton myasthenic syndrome. There was insufficient evidence to determine whether IVIG therapy was more effective than plasma exchange for Guillain-Barré syndrome. There was also insufficient evidence regarding paraprotein-associated polyneuropathy. No evidence of benefit was observed for secondary progressive multiple sclerosis or inclusion body myositis.

Adrenal Cortex Hormones↗

PubMed2005

Calcineurin inhibitor withdrawal from sirolimus-based therapy in kidney transplantation: a systematic review of randomized trials.

Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function, however, it also carries risk of acute rejection. We conducted a systematic review of randomized trials that involved CNI withdrawal from a sirolimus-based immunosuppressive regimen. The search strategy yielded six trials (n = 1047 patients) reported in eight publications. CNI withdrawal from sirolimus-based therapy, was associated with an increased risk of acute rejection (risk difference, 6%; 95% CI 2-10%, p = 0.002) but a higher creatinine clearance (mean difference, 7.49 mL/min; 95% CI 5.08-9.89 mL/min, p < 0.00001) at 1 year compared to continued CNI and sirolimus therapy. Graft loss (relative risk, 0.87; 95% CI 0.46-1.64, p = 0.66) and death (relative risk, 0.88; CI 0.40-1.96, p = 0.76) were similar in both groups at 1 year. Hypertension was significantly reduced in the CNI withdrawal group (relative risk, 0.56; 95% CI 0.40-0.78, p = 0.0006). CNI withdrawal from sirolimus-based therapy is associated with an increased risk of acute rejection in the short term with a significant improvement in renal function and a reduction in hypertension. Longer follow-up is needed to determine if these changes will result in a significant improvement in patient and graft survival.

Acute Disease↗

PubMed2005

Randomized controlled trials of aprotinin in cardiac surgery: could clinical equipoise have stopped the bleeding?

BACKGROUND: Aprotinin is a serine protease inhibitor used to limit perioperative bleeding and reduce the need for donated blood transfusions during cardiac surgery. Randomized controlled trials of aprotinin evaluating its effect on the outcome of perioperative transfusion have been published since 1987, and systematic reviews were conducted in 1992 and 1997. METHODS: A systematic search was conducted for all RCTs of aprotinin that used placebo controls or were open-label with no active control treatment. Data collected included the primary outcome, objective of each study, whether a systematic review was cited or conducted as part of the background and/or rationale for the study and the number of previously published RCTs cited. Cumulative meta-analyses were performed. RESULTS: Sixty-four randomized, controlled trials of aprotinin were found, conducted between 1987 and 2002, reporting an endpoint of perioperative transfusion. Median trial size was 64 subjects, with a range of 20 to 1784. A cumulative meta-analysis indicated that aprotinin greatly decreased the need for perioperative transfusion, stabilizing at an odds ratio of 0.25 (p < 10 - 6) by the 12th study, published in June of 1992. The upper limit of the confidence interval never exceeded 0.65 and results were similar in all subgroups. Citation of previous RCTs was extremely low, with a median of 20% of prior trials cited. Only 7 of 44 (15%) of subsequent reports referenced the largest trial (N = 1784), which was 28 times larger than the median trial size. CONCLUSIONS: This study demonstrates that investigators evaluating aprotinin were not adequately citing previous research, resulting in a large number of RCTs being conducted to address efficacy questions that prior trials had already definitively answered. Institutional review boards and journals could reduce the number of redundant trials by requiring investigators to conduct adequate searches for prior evidence and conducting systematic reviews.

Aprotinin↗

PubMed2005

Topical nonsteroidal anti-inflammatory drugs for corneal abrasions: meta-analysis of randomized trials.

OBJECTIVES: To determine the effectiveness of topical nonsteroidal anti-inflammatory drugs (NSAIDs) in traumatic corneal abrasions. METHODS: This was a systematic literature review and meta-analysis of randomized clinical trials (RCTs). The following databases were searched: MEDLINE (1966-2004), EMBASE (1980-2004), and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews (first quarter 2004). The structured search strategy included a RCT filter and the terms "cornea," "wounds and injuries," "trauma," "corneal diseases," "eye injuries," "anti-inflammatory agents, nonsteroidal" and specific trade names of topical NSAIDs. In addition, four journals in ophthalmology and emergency medicine were hand searched. Two authors independently reviewed citations from the literature searches. To be included, studies had to be RCTs evaluating topical NSAIDs in traumatic corneal abrasions. Trials were included regardless of language or whether they were unpublished or published. Exclusion criteria were corneal ulcers, nonrandomized studies, animal studies, or perioperative setting. Outcomes were pain scale scores at 24 hours and adverse effects. Two independent reviewers assessed four trial quality components: randomization, double blinding, reporting of withdrawals, and concealment of allocation. Weighted mean difference, using a random effects model, was calculated. RESULTS: Of the 200 citations identified, 11 RCTs met inclusion criteria. Eight trials were identified from the MEDLINE search, two from the EMBASE search, and one from conference proceedings. Seven trials enrolled fewer than 100 patients, and more than half of the studies were conducted in Europe. Five trials reported suitable data for analysis. The overall weighted mean difference for 459 patients was a reduction in pain by 1.30 points (95% confidence interval = -1.56 to -1.03) on the pain scale. Five of the trials met criteria for good quality. Transient stinging was a commonly noted adverse effect. CONCLUSIONS: Topical NSAIDs are effective analgesics for traumatic corneal abrasions.

Administration, Topical↗

PubMed2005

A pilot trial evaluating the clinical effects of prolonged storage of red cells.

The clinical consequences of prolonged storage of red cells have not been established. In this pilot study, we evaluated whether it would be feasible to provide a continuous supply of red cells stored <8 days. In addition, we examined the potential benefits attributed to "fresh" as compared to standard red cells in 66 critically ill and cardiac surgical patients. Nine patients were issued red cells but were not transfused. From the 57 remaining patients, the number of units transfused averaged 5.5 +/- 8.43 red cell units in the experimental group compared to 3.3 +/- 3.27 red cell units in the standard group (P = 0.25). The median storage time was 4 days in the experimental group compared to 19 days in the standard group (difference of 15 days; interquartile range of 12-16 days; P < 0.001). Overall, 73% of patients received red cells with storage times that corresponded to the treatment allocation more than 90% of the time. The group receiving red cells <8 days old tended to be older on average (68 +/- 8.54 yr versus 63 +/- 15.30 yr; P = 0.13) and have more comorbid illnesses (85% versus 65%; P = 0.09). In total, 27% of patients in the experimental group died or had a life-threatening complication as compared to 13% in the standard group (P = 0.31). There were no differences in prolonged respiratory, cardiovascular, or renal support after randomization (P > 0.05). A large clinical trial comparing red cell storage times is feasible and warranted given the limited available evidence.

Adult↗

PubMed2004

Turning a blind eye: the success of blinding reported in a random sample of randomised, placebo controlled trials.

OBJECTIVE: To examine the reporting and success of double blinding in a sample of randomised, placebo controlled trials from leading general medicine and psychiatry journals. METHODS: Identification of placebo controlled, randomised controlled trials from prespecified general medical and psychiatric journals indexed on Medline between 1 January 1998 and 1 October 2001, from which a random sample of 200 randomised clinical trials was chosen, of which 191 trials were evaluated. RESULTS: Only seven of the 97 (7%) general medicine trials provided evidence on the success of blinding, with five reporting that the success of blinding was imperfect. In trials from psychiatric journals, the success of blinding was reported in eight of the 94 trials, with four reporting that the blinding was imperfect. Overall, only four of the 191 (2%) trials assessed blinding in the participants and either the outcome assessors or the investigators. CONCLUSIONS: The current lack of reporting on the success of blinding provides little evidence that success of blinding is maintained in placebo controlled trials. Trialists and editors should make a concerted effort to incorporate, report, and publish such information and its potential effect on study results.

Double-Blind Method↗

PubMed2004

Transfusion of leukoreduced red blood cells may decrease postoperative infections: two meta-analyses of randomized controlled trials.

PURPOSE: To evaluate the efficacy and effectiveness of red blood cell leukoreduction in reducing postoperative infection, mortality and cancer recurrence, two meta-analyses of randomized controlled trials (RCTs) were conducted. METHODS: A systematic search of the scientific literature was conducted. The pooled relative risk ratio (RR) of developing an adverse postoperative outcome with either leukoreduced or non-leukoreduced blood was calculated using a random effects model. To better estimate the efficacy of leukoreduction, a second analysis of transfused patients only was conducted. RESULTS: Ten RCTs met inclusion criteria and eight provided separate data for patients randomized and transfused. The mean percentage of patients randomized but not transfused was 34%. For postoperative infection, the overall pooled RR was 0.76 [(95% confidence interval (CI): 0.54-1.08] for the "all patients randomized" analysis. For the "only patients transfused" analysis, the pooled RR became clinically and statistically significant (RR = 0.60 (95% CI: 0.38-0.93). For mortality, the pooled RR for the "all patients randomized" analysis was 0.71 (95% CI: 0.45-1.13) and 0.61 (95% CI: 0.36-1.04) for the "only patients transfused" analysis. When analyzing either all patients randomized or all patients transfused, there was no statistically significant difference in cancer recurrence rates (one study only). CONCLUSION: We demonstrated that patients who were transfused leukoreduced red blood cells might benefit from a decrease in postoperative infections. A decrease in mortality may have been realized if more patients had been enrolled in the various randomized trials. Including all patients randomized, regardless of whether or not they were actually transfused diluted the observed clinical benefit of leukoreduction.

Blood Transfusion↗

PubMed2004

Changes in body weight and serum lipid profile in obese patients treated with orlistat in addition to a hypocaloric diet: a systematic review of randomized clinical trials.

BACKGROUND: Obesity is a growing health concern in Canada and the United States, and pharmacologic therapies such as orlistat are being more commonly prescribed to assist with weight loss. OBJECTIVE: Our goal was to assess the efficacy and safety of orlistat compared with either placebo or an active control with regard to weight loss and serum lipid changes in overweight patients. DESIGN: We performed a systematic literature search of MEDLINE (1966 through December 2003) and the Cochrane Central Register of Controlled Trials. Relevant trials and reviews were searched by hand. Randomized trials comparing orlistat and a control and reporting changes in weight loss, serum lipids (total cholesterol, LDL cholesterol, HDL cholesterol, LDL:HDL, and triacylglycerols), or both in overweight and obese patients [body mass index (in kg/m2) > or =25] were included. RESULTS: Twenty-eight randomized trials met our inclusion criteria. Seventeen studies including 10,041 patients compared 3 x 120 mg orlistat/d with placebo or an inactive control along with a hypocaloric diet over a 1-y period. Relative risks (RRs) associated with clinically significant weight losses of 5% and 10% were 1.74 (95% CI: 1.57, 1.91) and 1.96 (1.74, 2.21), both favoring orlistat. Improvement in total cholesterol, LDL cholesterol, HDL cholesterol, and LDL:HDL were also greater with orlistat. Gastrointestinal events were more common with orlistat than with placebo [RR: 1.46 (1.37, 1.55)]. CONCLUSION: Our findings suggest that 3 x 120 mg orlistat/d is effective for improving both weight loss and serum lipid profiles in obese patients at low and high cardiovascular disease risk and in obese patients with type 2 diabetes.

Adult↗