The case of the misleading funnel plot.
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Bias↗
Biomedical subjects
Joseph Lau
Publications and source records attributed to Joseph Lau.
Amodiaquine combined with sulfadoxine/pyrimethamine versus artemisinin-based combinations for the treatment of uncomplicated falciparum malaria in Africa: a meta-analysis.
Drug resistance in Plasmodium falciparum is a major obstacle to malaria control. Artemisinin-based combination therapy (ACT) is being advocated to improve treatment efficacy and to delay development of resistance. Here we summarise the available data on the efficacy of amodiaquine plus sulfadoxine/pyrimethamine (AQ+SP) versus ACTs in the treatment of uncomplicated malaria in sub-Saharan Africa. We searched for randomised trials in which patients with uncomplicated malaria treated with AQ+SP were compared with those treated with either amodiaquine plus artesunate (AQ+AS), artesunate plus sulfadoxine/pyrimethamine (AS+SP) or artemether/lumefantrine (AL). Medline, EMBASE, Cochrane Central Register of Controlled Trials and reference lists up to July 2005 were searched. Two reviewers independently extracted the data. The primary outcome measure was treatment failure by Day 28. Outcome measures were combined using a random effects model. Seven randomised trials of 4472 children were included. Trial quality was generally high. Treatment failure of AQ+SP was significantly reduced compared with AS+SP (relative risk (RR)=0.56, 95% CI 0.42-0.75), but increased compared with AL (RR=2.80, 95% CI 2.32-3.39). The overall failure rate of AQ+SP was similar compared with AQ+AS (RR=1.12, 95% CI 0.81-1.54), but there was significant heterogeneity of results across the studies. All the treatment regimens were safe and well tolerated. AQ+SP should be considered in some settings before the full implementation of an ACT.
Africa↗
Preventing post-organ transplantation cytomegalovirus disease with ganciclovir: a meta-analysis comparing prophylactic and preemptive therapies.
BACKGROUND: Cytomegalovirus (CMV) causes significant morbidity and mortality in transplant recipients, but there is no consensus regarding the most appropriate prevention method. The goal of this meta-analysis was to compare the efficacy of universal prophylaxis and preemption using ganciclovir. METHODS: Literature searches for randomized and nonrandomized controlled trials of ganciclovir prophylaxis and preemption were conducted. Because of the lack of head-to-head trials, indirect comparisons of meta-analyses of the prevention strategies were performed. Meta-analyses were conducted using a random effects model to estimate the overall risk ratios for various clinical outcomes. We assessed the event rates for control groups across the trials for comparability. RESULTS: Literature searches identified 17 universal prophylaxis trials and 9 preemption trials with 1560 and 457 subjects, respectively. Overall event rates for CMV disease in control groups across the studies were similar (approximately 26%). The relative risk of CMV disease in prophylaxis trials was 0.34 (95% confidence interval, 0.24-0.48) when trials of patients with prophylaxis of short duration and trials that only evaluated patients with high-risk serostatus were excluded. The relative risk of CMV disease for study subjects in all preemption trials was 0.30 (95% confidence interval, 0.15-0.60), compared with that for control subjects. There was no statistically significant difference in CMV disease between prevention strategies. Similarly, no differences between strategies were found for all-cause mortality or rejection. There were insufficient data to adequately evaluate graft loss and opportunistic infection. CONCLUSIONS: On the basis of indirect comparisons of meta-analyses of prevention strategies, universal prophylaxis and preemption are equally effective in reducing the incidence of CMV disease.
Antiviral Agents↗
On the toxicity of chemotherapy for breast cancer--the need for vigilance.
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Antineoplastic Combined Chemotherapy Protocols↗
A systematic review of the effect of the Excebrane dialyser on biomarkers of lipid peroxidation.
BACKGROUND: Oxidative stress is prevalent in dialysis patients and has been implicated in the pathogenesis of cardiovascular disease and anaemia. We conducted a systematic review and meta-analysis to examine the effect of Excebrane, a vitamin E-coated cellulose-based dialyser, on circulating biomarkers of lipid peroxidation, as surrogate markers of oxidative stress. METHODS: The primary sources used to identify candidate studies included PubMed, the Cochrane Central Register of Controlled Trials, a bibliography provided by the dialyser manufacturer, and a manual search of abstracts from proceedings of scientific meetings and review articles. Studies were selected for analysis if their design included a comparator group (primarily within patient comparison, i.e. pre- and post-study evaluations). For the meta-analysis, we computed the overall change of the outcome from baseline using a random-effects model. A supplemental analysis was performed in which the absolute levels of these biomarkers of lipid peroxidation were converted to a common unit by calculating standardized effect sizes. RESULTS: Fourteen peer-reviewed articles met the criteria. The studies consisted of 11 single arm, one randomized crossover and two randomized controlled trials, with a total of 37 to 158 evaluable patients, according to the outcome of interest analysed. Due to the paucity of randomized trials, the meta-analysis was limited to the Excebrane arm of each study. When the studies were combined according to similar measurement units, the overall mean decrease in malondialdehyde (MDA) level was -0.3 mM (95% CI, -0.5 to -0.1 mM; seven studies) and -0.8 nmol/mg low-density lipoprotein (LDL) (95% CI, -1.3 to -0.4 nmol/mg LDL; three studies), respectively. The summary estimate revealed a non-significant decrease in pre-dialysis thiobarbituric acid reactive substances (TBARS) level of 0.4 microM (95% CI, -1.2 to 0.4 microM; three studies). When the MDA and TBARS studies were combined using the standardized effect size, the mean decrease in these biomarkers of lipid peroxidation was statistically significant at -1.7 units (95% CI, -2.7, -0.7 units; 13 studies). A meta-analysis on the effect of Excebrane on pre-dialysis levels of oxidized-LDL could not be performed due to study heterogeneity. CONCLUSION: The conversion of dialysis patients to a vitamin E-coated dialyser is associated with an improvement in circulating biomarkers of lipid peroxidation, which is of potential clinical benefit.
Antioxidants↗
Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review.
Greater fish oil consumption has been associated with reduced CVD risk, although the mechanisms are unclear. Plant-source oil omega-3 fatty acids (ALA) have also been studied regarding their cardiovascular effect. We conducted a systematic review of randomized controlled trials that evaluated the effect of consumption of fish oil and ALA on commonly measured serum CVD risk factors, performing meta-analyses when appropriate. Combining 21 trials evaluating lipid outcomes, fish oil consumption resulted in a summary net change in triglycerides of -27 (95% CI -33, -20)mg/dL, in HDL cholesterol of +1.6 (95% CI +0.8, +2.3)mg/dL, and in LDL cholesterol of +6 (95% CI +3, +8)mg/dL. There was no effect of fish oil on total cholesterol. Across studies, higher fish oil dose and higher baseline levels were associated with greater reductions in serum triglycerides. Overall, the 27 fish oil trials evaluating Hgb A(1c) or FBS found small non-significant net increases compared to control oils. Five studies of ALA were inconsistent in their effects on lipids, Hgb A(1c) or FBS. Four studies investigating the effects of omega-3 fatty acids on hs-CRP were also inconsistent and non-significant. The evidence supports a dose-dependent beneficial effect of fish oil on serum triglycerides, particularly among people with more elevated levels. Fish oil consumption also modestly improves HDL cholesterol, increases LDL cholesterol levels, but does not appear to adversely affect glucose homeostasis. The evidence regarding the effects of omega-3 fatty acids on hs-CRP is inconclusive, as are data on ALA.
Biomarkers↗
Clinical practice guidelines in nephrology--for worse or for better.
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Evidence-Based Medicine↗
n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review.
Studies on the relation between dietary n-3 fatty acids (FAs) and cardiovascular disease vary in quality, and the results are inconsistent. A systematic review of the literature on the effects of n-3 FAs (consumed as fish or fish oils rich in eicosapentaenoic acid and docosahexaenoic acid or as alpha-linolenic acid) on cardiovascular disease outcomes and adverse events was conducted. Studies from MEDLINE and other sources that were of > or =1 y in duration and that reported estimates of fish or n-3 FA intakes and cardiovascular disease outcomes were included. Secondary prevention was addressed in 14 randomized controlled trials (RCTs) of fish-oil supplements or of diets high in n-3 FAs and in 1 prospective cohort study. Most trials reported that fish oil significantly reduced all-cause mortality, myocardial infarction, cardiac and sudden death, or stroke. Primary prevention of cardiovascular disease was reported in 1 RCT, in 25 prospective cohort studies, and in 7 case-control studies. No significant effect on overall deaths was reported in 3 RCTs that evaluated the effects of fish oil in patients with implantable cardioverter defibrillators. Most cohort studies reported that fish consumption was associated with lower rates of all-cause mortality and adverse cardiac outcomes. The effects on stroke were inconsistent. Evidence suggests that increased consumption of n-3 FAs from fish or fish-oil supplements, but not of alpha-linolenic acid, reduces the rates of all-cause mortality, cardiac and sudden death, and possibly stroke. The evidence for the benefits of fish oil is stronger in secondary- than in primary-prevention settings. Adverse effects appear to be minor.
Cardiovascular Diseases↗
Differences in characteristics of nocturnal enuresis between children and adolescents: a critical appraisal from a large epidemiological study.
OBJECTIVE: To evaluate any differences in the characteristics of primary nocturnal enuresis (PNE) between younger enuretic children and adolescents. SUBJECTS AND METHODS: In all, 21 000 questionnaires designed to determine the presence or absence of bed-wetting, diurnal incontinence, frequency of wetting, systemic illness, and family history, were sent to children aged 5-19 years from 67 kindergartens, primary schools and secondary schools randomly selected by a computer from different areas in Hong Kong. In addition, questions were asked to evaluate when and how the parents became aware that bed-wetting is a significant medical problem deserving attention in children after the age of 5 years. RESULTS: Of the 21,000 questionnaires distributed, 16 512 (78.6%) were completed. Among the respondents, 512 children (302 boys, 210 girls) had PNE; of these, 106 (20.7%) also had daytime incontinence. There was a marked reduction in the overall prevalence of PNE with advancing age. At 5 years old, 16.1% of children had PNE (20.7% boys, 10.8% girls; at age 9 and 19 years, 3.14% and 2.2% of children had PNE, respectively. However, this reduction was significantly more apparent among those with mild enuretic symptoms (wet <3 nights/week) than in those with more frequent bed-wetting. Furthermore, younger enuretic children behaved very differently from adolescents and older patients. As age increased there was a significant tendency towards more severe enuretic symptoms. At age 5 years, 14.3% of enuretic children wet 7 nights/week, compared with 48.3% at age 19 years (P < 0.001). In addition, significantly more adolescent boys aged >10 years had daytime urinary incontinence than had enuretic children aged < or = 10 years (32% vs 14.6%, respectively, P < 0.001). Most (89%) parents only became aware that bed-wetting was a significant medical problem deserving attention through material in the mass media over the past 3-4 years. CONCLUSIONS: The present finding suggesting that PNE spontaneously resolves with increasing age probably applies only to those with mild enuretic symptoms. There are significant differences in characteristics between younger enuretic children and older subjects. As age increases there is an increasing proportion of enuretic patients with more severe bed-wetting. Enuretic children aged >10 years and adolescents have significantly more daytime urinary symptoms and incontinence. The previously reported low prevalence of PNE in Hong Kong was probably due to parental indifference to the problem.
Adolescent↗
A population-based survey on infant feeding practice (0-2 years) in Hong Kong: breastfeeding rate and patterns among 3,161 infants below 6 months old.
The prevalence of breastfeeding for the first 6 months in infants has been low in Hong Kong since the 1970s. In order to develop effective breastfeeding policies and promotion programs, an appraisal of feeding practices and factors related to initiation and early cessation of breastfeeding is necessary. A survey with a population-based representative sample was conducted to determine social-demographic, personal and cultural factors that influenced decision, duration and practice of infant feeding among infants 0-24 months old. This paper focuses on infants below 6 months old to study factors related to decision, duration and practice of breastfeeding. In 1993, 7,298 healthy infants were recruited from 46 Maternal-and-Child-Health-Clinics (MCHC) throughout Hong Kong, of whom 3161 were below 6 months old. The mother reported her feeding decision, duration and practice in a questionnaire. Breastfeeding rate was found to be very low (8.4%) for infants below 6 months old. Only 50.9% infants were breastfed. Infant formulae were widely given among partially breastfed infants. 45% mothers were full-time employed. Most mothers were aware of the benefits of breastfeeding to the infants and themselves. Husbands (43.3%) were regarded the most influential on initiation and duration on breastfeeding. Restricted food varieties (54%), sore nipple and breast engorgement (67%), perceived home confinement (41.5%) and perceived inadequate milk supply (31.7%) were major concerns upon breastfeeding. Furthermore, 76.9% mothers turned to MCHC staff for advice when they encountered difficulties during breastfeeding. In conclusion, the survey collected population-based representative data on factors determining initiation and early cessation of breastfeeding in Hong Kong in 1993. The findings will serve as a cornerstone in understanding the evolution of breastfeeding practice in Hong Kong. It merits further study to investigate how the confounders interplay to modulate initiation, duration and patterns of breastfeeding.
Adult↗
Local literature bias in genetic epidemiology: an empirical evaluation of the Chinese literature.
BACKGROUND: Postulated epidemiological associations are subject to several biases. We evaluated whether the Chinese literature on human genome epidemiology may offer insights on the operation of selective reporting and language biases. METHODS AND FINDINGS: We targeted 13 gene-disease associations, each already assessed by meta-analyses, including at least 15 non-Chinese studies. We searched the Chinese Journal Full-Text Database for additional Chinese studies on the same topics. We identified 161 Chinese studies on 12 of these gene-disease associations; only 20 were PubMed-indexed (seven English full-text). Many studies (14-35 per topic) were available for six topics, covering diseases common in China. With one exception, the first Chinese study appeared with a time lag (2-21 y) after the first non-Chinese study on the topic. Chinese studies showed significantly more prominent genetic effects than non-Chinese studies, and 48% were statistically significant per se, despite their smaller sample size (median sample size 146 versus 268, p < 0.001). The largest genetic effects were often seen in PubMed-indexed Chinese studies (65% statistically significant per se). Non-Chinese studies of Asian-descent populations (27% significant per se) also tended to show somewhat more prominent genetic effects than studies of non-Asian descent (17% significant per se). CONCLUSION: Our data provide evidence for the interplay of selective reporting and language biases in human genome epidemiology. These biases may not be limited to the Chinese literature and point to the need for a global, transparent, comprehensive outlook in molecular population genetics and epidemiologic studies in general.
Asian People↗
Effects of omega-3 fatty acids on coronary restenosis, intima-media thickness, and exercise tolerance: a systematic review.
Greater omega-3 fatty acid consumption is associated with reduced cardiovascular disease risk. Though the mechanisms of their effect are unclear, they may involve lesion formation and heart function. We conducted a systematic review of the clinical literature on the effect of omega-3 fatty acids on measures of vascular structure and function. We included studies that assessed fish and plant sources of omega-3 fatty acids on coronary artery restenosis after angioplasty, carotid IMT, and exercise capacity. Compared to placebo, the summary risk ratio of coronary artery restenosis with fish oil is 0.87 (95% CI 0.73, 1.05) across 12 randomized controlled trials. Two prospective studies reported increased carotid IMT, whereas two cross-sectional studies reported a reduction of IMT, with fish, fish oil or ALA consumption. Three randomized trials and three uncontrolled studies reported small non-significant improvements in exercise capacity with fish oil. Overall, little or no effect of fish oil was found for a variety of markers of cardiovascular disease risk. There are insufficient studies to draw conclusions about the effect of ALA. The dearth of long term data on fish consumption or omega-3 fatty acid supplementation on measures of cardiovascular disease risk severely limits our ability to draw definitive conclusions at this time.
Carotid Arteries↗
High-dosage vitamin E supplementation and all-cause mortality.
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Data Interpretation, Statistical↗
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↗