High-dosage vitamin E supplementation and all-cause mortality.
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Data Interpretation, Statistical↗
Biomedical subjects
Joseph Lau
Publications and source records attributed to Joseph Lau.
Challenges in systematic reviews of diagnostic technologies.
Diagnostic tests are critical components of effective health care. They help determine treatments that are most beneficial for a given patient. Their assessment is a complex process that includes such challenges as a dearth of studies that evaluate clinical outcomes and lack of data on use of the test in realistic clinical settings. The methodologic quality of studies of diagnostic tests also lags behind the quality of studies of therapeutic interventions. Statistical methods to combine diagnostic accuracy data are more complex and not as well developed, leading to difficulties in the interpretation of results. The Agency for Healthcare Research and Quality Technology Assessment Program has adopted a 6-level framework for evaluating diagnostic technologies. The model emphasizes the need for systematic reviews of diagnostic test studies to go beyond the assessment of technical feasibility and accuracy to examine the impact of the test on health outcomes. In this paper, we use examples from 3 Evidence-based Practice Center reports to illustrate 3 challenges reviewers may face when reviewing diagnostic test literature: finding relevant studies, assessing methodologic quality of diagnostic accuracy studies, and synthesizing studies that evaluate tests in different patient populations or use different outcomes.
Diagnostic Techniques and Procedures↗
Effects of fish oil supplementation on kidney transplantation: a systematic review and meta-analysis of randomized, controlled trials.
The objective of this study was to assess the effects of omega-3 fatty acid supplementation on various kidney transplant-related outcomes. A systematic review and meta-analysis was performed of published randomized, controlled trials (RCT). There were 16 kidney transplant RCT with a total of 812 patients. All trials evaluated fish oil with dosages that ranged from 1.2 to 5.4 g/d. No consistent benefits were observed for any outcome with the exception of a modest benefit on triglycerides. A meta-analysis of rejection episodes found no significant benefit on either early (<6 mo posttransplantation) or late episodes. The overall relative risk of having at least one rejection episode in those who received fish oil was 0.91 (95% confidence interval 0.74 to 1.10) in four studies with a follow-up of 1 yr. A meta-analysis of eight RCT of graft survival found no significant benefit (relative risk 1.00, 95% confidence interval 0.96 to 1.05). The available data (mostly derived from older studies with important methodologic limitations) do not demonstrate a consistent, clinically important benefit of fish oil in kidney transplantation.
Clinical Trials as Topic↗
Generalized low bone mass of girls with adolescent idiopathic scoliosis is related to inadequate calcium intake and weight bearing physical activity in peripubertal period.
Generalized low bone mass has been well documented in patients with adolescent idiopathic scoliosis (AIS). However, studies linking calcium-intake (CA), weight-bearing physical-activity (PA) and bone mass of AIS are lacking. We aimed to study the relationship between CA, PA and bone mass in AIS girls and compared to those of healthy non-AIS controls during the peripubertal period. Newly diagnosed AIS girls (n=596) aged 11-16 years with Cobb angle >/=10 degrees were recruited to compare with age-matched healthy girls (n=302) in a cross-sectional study. Anthropometric parameters, pubertal status, CA and PA were assessed. Areal bone mass of lumbar spine and femoral neck, and volumetric bone mass of distal radius and tibia were determined by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography, respectively. The results showed that weight and body mass index (BMI) of AIS were lower than the controls (P<0.05). Corrected height and arm span of AIS were longer than those of controls from 13 years onwards (P<0.02). Median CA of AIS was <410 mg/day across the ages and did not differ from the controls (P=0.063). Median PA of AIS (1.6 h/day) was lower than the controls (1.8 h/day) (P=0.025). Bone mass of AIS was on average 6.5% lower than controls across the ages (P<0.05). CA and PA were significantly correlated with bone mass of AIS (P<0.04). Multivariate analysis showed that AIS in girls was associated with lower bone mass, and that both CA and PA were independent predictors of bone mass in AIS. In conclusion, AIS girls were found to have lower body weight and BMI, longer segmental lengths and generalized low bone mass. Inadequate calcium intake and weight-bearing physical activity were significantly associated with low bone mass in AIS girls during the peripubertal period. The importance of preventing generalized osteopenia in the control of AIS progression during the peripubertal period warrants further study.
Absorptiometry, Photon↗
Long-term effectiveness of weight-loss interventions in adults with pre-diabetes: a review.
OBJECTIVE: To assess the effectiveness of weight-loss and weight-control interventions for adults with pre-diabetes (impaired fasting glucose and impaired glucose tolerance), an important risk factor for the development of type 2 diabetes. METHODS: Computerized searches were conducted of multiple electronic bibliographic databases up to August 2003. Randomized controlled trials in any language were selected that examined weight-loss or weight-control strategies using at least one dietary, physical activity, or behavioral intervention, and with a follow-up interval of a per thousand yen12 months. Effects were combined using a random effects model. RESULTS: Studies were identified, with a total of 5168 participants. Follow-up ranged from 1 to 10 years. Quantitative synthesis was limited by the heterogeneity of populations, settings, and interventions, and by the small number of studies that examined outcomes other than weight. Overall, compared to usual care, four studies with a follow-up of 1 year reduced weight by 2.8 kg (95% confidence interval [CI]=1.0-4.7) (3.3% of baseline body weight) and decreased body mass index by 1.4 kg/m(2) (CI=0.5-2.3). Weight loss at 2 years was 2.7 kg (CI=1.9-3.4) (two studies). Modest improvements were noted in the few studies that examined glycemic control, blood pressure, and lipid concentrations (p >0.05). The incidence of diabetes was significantly lower in the intervention groups versus the controls in three of five studies examining this outcome at 3 to 6 years follow-up. CONCLUSIONS: Overall, weight-loss strategies using dietary, physical activity, or behavioral interventions produced significant improvements in weight among persons with pre-diabetes, and a significant decrease in diabetes incidence. Further work is needed on the long-term effects of these interventions on morbidity and mortality and on how to implement these interventions in the community setting.
Adult↗
Topical anesthetics for dermal instrumentation: a systematic review of randomized, controlled trials.
STUDY OBJECTIVE: We compare the analgesic efficacy of topical anesthetics for dermal instrumentation with conventional infiltrated local anesthesia and also compare topically available amide and ester agents with a eutectic mixture of local anesthetics (EMLA). METHODS: We conducted a systematic review of randomized, controlled trials. Relevant literature was identified through searches of MEDLINE, Cochrane Central Register of Controlled Trials, and the Excerpta Medica Database Drugs and Pharmacology. We limited the type of procedures to puncture of intact skin with a needle. The primary outcome was analgesic efficacy, reflected in the patient's self-report of pain intensity during dermal instrumentation. Where possible, quantitative methods were used to summarize the results. RESULTS: We identified 25 randomized controlled trials including 2,096 subjects. The results of the trials comparing the efficacy of EMLA with infiltrated local anesthetic were inconsistent. Qualitative analysis demonstrated comparable analgesic efficacy between liposome-encapsulated lidocaine and EMLA. The weighted mean difference in 100-mm visual analogue scale pain scores favored topical tetracaine over EMLA (-8.1 mm; 95% confidence interval -15.6 mm to -0.6 mm). Liposome-encapsulated tetracaine provided greater analgesia than EMLA according to the weighted mean difference in 100-mm visual analogue scale scores (-10.9 mm; 95% confidence interval -15.9 mm to -5.9 mm). CONCLUSION: EMLA may be an effective, noninvasive means of analgesia before dermal procedures. However, we identified 3 topical anesthetics that are at least as efficacious as EMLA: tetracaine, liposome-encapsulated tetracaine, and liposome-encapsulated lidocaine. Liposomal lidocaine is commercially available in the United States and offers a more rapid onset and less expensive alternative to EMLA.
Administration, Cutaneous↗
Comparative efficacy and costs of various topical anesthetics for repair of dermal lacerations: a systematic review of randomized, controlled trials.
STUDY OBJECTIVES: To compare the efficacy of infiltrated local anesthesia with topical anesthesia for repair of dermal laceration, to analyze the efficacy of single or multicomponent topical anesthetics, and to identify topical formulations that are potentially less costly and equally efficacious as cocaine-containing topical anesthetics. DESIGN: Systematic review of randomized controlled trials. SETTING: University-affiliated hospital. PATIENTS: Pediatric and adult subjects. MEASUREMENTS AND MAIN RESULTS: Twenty-two trials that randomized more than 3000 patients were identified. The majority of studies demonstrated equivalent or superior analgesic efficacy for topical formulations compared with conventional intradermal infiltration. We found that cocaine is not a mandatory component of topical anesthesia. The literature discloses no significant difference in anesthetic efficacy between topical tetracaine-epinephrine-cocaine and each of the following 6 cocaine-free formulations: lidocaine-epinephrine-tetracaine, lidocaine-epinephrine, tetracaine-phenylephrine, tetracaine-lidocaine-phenylephrine, bupivicaine-norepinephrine, or prilocaine-phenylephrine. CONCLUSION: Topical anesthetics are an efficacious, noninvasive means of providing analgesia before suturing of dermal lacerations. The use of cocaine-containing topical anesthetics can no longer be justified in light of its high cost and potential adverse effects. We have summarized the evidence, mostly favorable, supporting the use of various non-cocaine-containing topical anesthetics.
Anesthetics, Local↗
Does the evidence support the use of spinal and epidural anesthesia for surgery?
When spinal and epidural anesthesia were introduced into clinical practice, their primary use was as an alternative to general anesthesia. Later, largely as a result of the realization that opioids could be safely and effectively used to produce selective spinal analgesia, spinal and epidural (neuraxial) analgesia began to be used specifically for the treatment of perioperative pain. We present a systematic review of the literature on neuraxial anesthesia and analgesia, new meta-analyses that illustrate the powerful effect of improvements in perioperative safety in general on the ability of neuraxial techniques to make a difference, and a consideration of why a literature analysis does not provide clear answers.
Analgesia, Epidural↗
In an empirical evaluation of the funnel plot, researchers could not visually identify publication bias.
BACKGROUND AND OBJECTIVE: Publication bias and related biases can lead to overly optimistic conclusions in systematic reviews. The funnel plot, which is frequently used to detect such biases, has not yet been subjected to empirical evaluation as a visual tool. We sought to determine whether researchers can correctly identify publication bias from visual inspection of funnel plots in typical-size systematic reviews. METHODS: A questionnaire with funnel plots containing 10 studies each (the median number in medical meta-analyses) was completed by 41 medical researchers, including clinical research fellows in a meta-analysis class, faculty in clinical care research, and experienced systematic reviewers. RESULTS: On average, participants correctly identified 52.5% (95% CI 50.6-54.4%) of the plots as being affected or unaffected by publication bias. The weighted mean percent correct, which adjusted for the fact that asymmetric plots are more likely to occur in the presence of publication bias, was also low (48.3 to 62.8%, depending on the presence or absence of publication bias and heterogeneous study effects). CONCLUSION: Researchers who assess for publication bias using the funnel plot may be misled by its shape. Authors and readers of systematic reviews need to be aware of the limitations of the funnel plot.
Humans↗
Reading and critically appraising systematic reviews and meta-analyses: a short primer with a focus on hepatology.
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Gastroenterology↗
A systematic review and meta-analysis of the impact of omega-3 fatty acids on selected arrhythmia outcomes in animal models.
Epidemiological studies and clinical trials report the beneficial effects of fish or fish oil consumption on cardiovascular disease outcomes including sudden death. We performed a systematic review of the literature on controlled animal studies that assessed the effects of omega-3 fatty acids on selected arrhythmia outcomes. On the basis of predetermined criteria, 27 relevant animal studies were identified; 23 of these were feeding studies, and 4 were infusion studies. Across species, fish oil, eicosapentaenoic acid, and/or docosahexaenoic acid appear to have beneficial effects on ventricular tachycardia (VT) and fibrillation (VF) in ischemia- but not reperfusion-induced arrhythmia models; no effect on the incidence of death and infarct size; and inconsistent results with regard to arrhythmia score, VF threshold, ventricular premature beats or length of time in normal sinus rhythm, compared to omega-6, monounsaturated, or saturated fatty acids, and no treatment controls. In a meta-analysis of 13 studies using rat models, fish oil but not alpha-linolenic acid supplementation showed a significant protective effect for ischemia- and reperfusion-induced arrhythmias by reducing the incidence of VT and VF. It is not known whether omega-3 fatty-acid supplementation has antiarrhythmic effects in other disease settings not related to ischemia.
Animals↗
Caveat for a cumulative meta-analysis.
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Data Interpretation, Statistical↗
Systemic administration of local anesthetics to relieve neuropathic pain: a systematic review and meta-analysis.
We reviewed randomized controlled trials to determine the efficacy and safety of systemically administered local anesthetics compared with placebo or active drugs. Of 41 retrieved studies, 27 trials of diverse quality were included in the systematic review. Ten lidocaine and nine mexiletine trials had data suitable for meta-analysis (n = 706 patients total). Lidocaine (most commonly 5 mg/kg IV over 30-60 min) and mexiletine (median dose, 600 mg daily) were superior to placebo (weighted mean difference on a 0-100 mm pain intensity visual analog scale = -10.60; 95% confidence interval: -14.52 to -6.68; P < 0.00001) and equal to morphine, gabapentin, amitriptyline, and amantadine (weighted mean difference = -0.60; 95% confidence interval: -6.96 to 5.75) for neuropathic pain. The therapeutic benefit was more consistent for peripheral pain (trauma, diabetes) and central pain. The most common adverse effects of lidocaine and mexiletine were drowsiness, fatigue, nausea, and dizziness. The adverse event rate for systemically administered local anesthetics was more than for placebo but equivalent to morphine, amitriptyline, or gabapentin (odds ratio: 1.23; 95% confidence interval: 0.22 to 6.90). Lidocaine and mexiletine produced no major adverse events in controlled clinical trials, were superior to placebo to relieve neuropathic pain, and were as effective as other analgesics used for this condition.
Anesthetics, Local↗
The epidemiology of cancer pain.
We identified 28 epidemiological surveys by applying a sensitive search in Medline and CancerLit databases, supplemented by hand searches. Only two surveys enrolled more than 10,000 patients with cancer. The remaining were hospital or clinic-based surveys of at most a few hundred patients. Fourteen surveys were conducted in the United States. The majority of the remaining studies were conducted in Europe (Finland, France, Germany, UK/Ireland). No single survey identified a prevalence of any type of pain below 14%. The prevalence of pain reported in these surveys varies with the specific type of pain (e.g., breakthrough pain) and/or population studied. Based on these surveys an aggregate statement could not be deduced regarding the correlation between the occurrence of pain and patient factors, disease characteristics, the setting in which care is provided (e.g., primary care or specialized oncology or pain treatment clinics), or specific treatments directed towards the underlying disease and its associated pain. However, these surveys suggest that a significant number of patients with cancer worldwide will, during the course of their disease, experience pain that requires medical and/or other treatment.
Epidemiologic Studies↗
Long-term effectiveness of lifestyle and behavioral weight loss interventions in adults with type 2 diabetes: a meta-analysis.
BACKGROUND: Most persons with type 2 diabetes are overweight, and obesity worsens the metabolic and physiologic abnormalities associated with diabetes. Our objective was to assess the effectiveness of lifestyle and behavioral weight loss and weight control interventions in adults with type 2 diabetes. METHODS: Studies were obtained from searches of multiple electronic bibliographic databases, supplemented with hand searches of selected journals and consultation with experts in obesity research. Studies were included if they were published or unpublished randomized controlled trials in any language that examined weight loss or weight control strategies using one or more dietary, physical activity, or behavioral interventions, with a follow-up interval of at least 12 months. Effects were combined using a random-effects model. RESULTS: The 22 studies of weight loss interventions identified yielded a total of 4659 participants with a follow-up of 1 to 5 years. The pooled weight loss for any intervention in comparison with usual care among 585 subjects was 1.7 kg (95% confidence interval [CI]: 0.3 to 3.2 kg), or 3.1% of baseline body weight among 511 subjects. Among 126 persons who underwent a physical activity and behavioral intervention, those who also received a very low-calorie diet lost 3.0 kg (95% CI: -0.5 to 6.4 kg), or 1.6% of baseline body weight, more than persons who received a low-calorie diet. Among 53 persons who received identical dietary and behavioral interventions, those who received a more intense physical activity intervention lost 3.9 kg (95% CI: -1.9 to 9.7 kg), or 3.6% of baseline body weight, more than those who received a less intense or no physical activity intervention. Comparison groups often achieved substantial weight loss (up to 10.0 kg), minimizing between-group differences. Changes in glycated hemoglobin level generally corresponded to changes in weight and were not substantial when between-group differences were examined. CONCLUSION: Weight loss strategies involving dietary, physical activity, or behavioral interventions were associated with small between-group improvements in weight. These results were minimized by weight loss in the comparison group, however, and examination of individual study arms revealed that multicomponent interventions, including very low-calorie diets or low-calorie diets, may hold promise for achieving weight loss in adults with type 2 diabetes.
Behavior Therapy↗
Effects of statins on vascular structure and function: a systematic review.
PURPOSE: Statins reduce cardiovascular events by more than can be explained by their effects on lipids. We conducted a systematic review of how statins affect vascular structure and function, differences among statins, and correlations between the effects of statins on vascular outcomes and either lipid levels or cardiovascular outcomes. METHODS: We primarily searched MEDLINE (1980 to March 2004) to identify all studies with at least 10 subjects that reported the effects of currently available statins on coronary artery stenosis, carotid intima-media thickness, and endothelial function (excluding studies of drug combinations and subjects with organ transplants). Meta-analyses were performed when feasible. RESULTS: Statins decrease the progression and increase the regression of coronary artery lesions and luminal narrowing. Compared with placebo, statins decrease the likelihood of coronary artery restenosis (summary risk ratio = 0.85; 95% confidence interval: 0.77 to 0.95). Statins appear to slow the progression of carotid artery intima-media thickness. Although the effect of statins on coronary endothelial function is uncertain, statins appear to improve peripheral endothelial function. There is no conclusive evidence to suggest that individual statins differ in their effects on these outcomes. Studies generally found weak or no correlation between the effects of statins on vascular outcomes and lipid levels. No study showed a correlation between vascular effect and clinical outcome. CONCLUSION: Statins slow the progression of, and may reverse, atherosclerosis. The magnitude of these effects, however, is small compared with the effects of statins on cardiovascular events. Statins also improve measures of vascular function, which may contribute to their clinical benefits. There is insufficient evidence to suggest that individual statins differ in their vascular effects.
Cardiovascular Diseases↗
Insulin therapy for critically ill hospitalized patients: a meta-analysis of randomized controlled trials.
BACKGROUND: Hyperglycemia is common in critically ill hospitalized patients, and it is associated with adverse outcomes, including increased mortality. The objective of this meta-analysis was to determine the effect of insulin therapy initiated during hospitalization on mortality in adult patients with a critical illness. METHODS: An electronic search in the English-language articles of MEDLINE and the Cochrane Controlled Clinical Trials Register and a hand search of key journals and relevant review articles were performed. Randomized controlled trials that reported mortality data on critically ill hospitalized adult patients who were treated with insulin were selected. Data on patient demographics, hospital setting, intervention (formulation and dosage of insulin, delivery method, and duration of therapy), mortality outcomes, adverse events, and methodological quality were extracted. RESULTS: Thirty-five trials met the inclusion criteria. Combining data from all trials using a random-effects model showed that insulin therapy decreases short-term mortality by 15% (relative risk [RR], 0.85; 95% confidence interval [CI], 0.75-0.97). In subgroup analyses, insulin therapy decreased mortality in the surgical intensive care unit (RR, 0.58; 95% CI, 0.22-0.62), when the aim of therapy was glucose control (RR, 0.71; 95% CI, 0.54-0.93), and in patients with diabetes mellitus (RR, 0.73; 95% CI, 0.58-0.90). A near-significant trend toward decreasing mortality was seen in patients with acute myocardial infarction who did not receive reperfusion therapy (RR, 0.84; 95% CI, 0.71-1.00). No randomized trials of insulin in the medical intensive care unit were identified. CONCLUSION: Insulin therapy initiated in the hospital in critically ill patients has a beneficial effect on short-term mortality in different clinical settings.
Adult↗
Clinical practice guidelines for chronic kidney disease in adults: Part II. Glomerular filtration rate, proteinuria, and other markers.
The Kidney Disease Outcome Quality Initiative of the National Kidney Foundation published clinical practice guidelines on chronic kidney disease in February 2002. Of the 15 guidelines, the first six are of greatest relevance to family physicians. Part II of this two-part review covers guidelines 4, 5, and 6. Glomerular filtration rate is the best overall indicator of kidney function. It is superior to the serum creatinine level, which varies with age, sex, and race and often does not reflect kidney function accurately. The glomerular filtration rate can be estimated using prediction equations that take into account the serum creatinine level and some or all of specific variables (age, sex, race, body size). In many patients, estimates of the glomerular filtration rate can replace 24-hour urine collections for creatinine clearance measurements. Urine dipsticks generally are acceptable for detecting proteinuria. To quantify proteinuria, the ratio of protein or albumin to creatinine in an untimed (spot) urine sample is an accurate alternative to measurement of protein excretion in a 24-hour urine collection. Patients with persistent proteinuria have chronic kidney disease. Other techniques for evaluating patients with chronic kidney disease include examination of urinary sediment, urine dipstick testing for red and white blood cells, and imaging studies of the kidneys (especially ultrasonography). These techniques also can help determine the underlying cause of chronic kidney disease. Family physicians should weigh the value of the National Kidney Foundation guidelines for their clinical practice based on the strength of evidence and perceived cost-effectiveness until additional evidence becomes available on the usefulness of the recommended quality indicators.
Adult↗