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Biomedical subjects

J Lau

Publications and source records attributed to J Lau.

At least 163 records · Page 9Linked to original sources
PubMed1996

Single or multiple daily doses of aminoglycosides: a meta-analysis.

OBJECTIVE: To assess relative efficacy and toxicity of aminoglycosides given by single daily dose compared with multiple daily doses. DESIGN: Meta-analysis of 21 randomised trials identified through MEDLARS (1966 to January 1995). Data were overviewed with fixed effects and random effects models and with meta-regression analysis. SUBJECTS: Total of 3091 patients with bacterial infection, most without pre-existing renal disease. INTERVENTIONS: Patients were randomized to receive aminoglycosides once daily or multiple times daily with similar total daily dose. MAIN OUTCOME MEASURES: Clinical failure of treatment, nephrotoxicity, ototoxicity, and mortality. RESULTS: Single daily dose regimen produced a non-significant decrease in risk of antibiotic failures (random effects risk ratio 0.83 (95% confidence interval 0.57 to 1.21)). Benefit of once daily dosing was greater when the percentage of pseudomonas isolates in a trial was larger. Once daily administration reduced risk of nephrotoxicity (fixed effects risk ratio 0.74 (0.54 to 1.00)). Similar trends were noted for patients with febrile neutropenia and for children. There was no significant difference in ototoxicity between the two dosing regimens, but the power of the pooled trials to detect a meaningful difference was low. There was no significant difference in mortality. CONCLUSIONS: Once daily administration of aminoglycosides in patients without pre-existing renal impairment is as effective as multiple daily dosing, has a lower risk of nephrotoxicity, and no greater risk of ototoxicity. Given the additional convenience and reduced cost, once daily dosing should be the preferred mode of administration.

Aminoglycosides↗
PubMed1996

A meta-analysis of the relative efficacy and toxicity of Pneumocystis carinii prophylactic regimens.

BACKGROUND: Finding the optimal strategy for Pneumocystis carinii prophylaxis in patients with human immunodeficiency virus infection can be problematic. Several prophylactic regimens are available, but their relative efficacy and tolerance are not well understood. METHODS: A meta-analysis overviewed 35 randomized trials comparing different regimens for P carinii prophylaxis directly or with placebo. Analyses were based on intention-to-treat. On-treatment data were also analyzed when available. RESULTS: Regardless of dose, sulfamethoxazole-trimethoprim was almost universally effective for patients who tolerated it. The risk of discontinuing sulfamethoxazole-trimethoprim because of side effects decreased by 43% (95% confidence interval, 30% to 54%) if one double-strength tablet was given three times a week instead of daily. For dapsone, among 100 patients given 100 mg daily instead of twice a week for 1 year (primary prophylaxis), seven fewer patients would develop P carinii pneumonia, but 17 more would have significant toxic reactions. Aerosolized pentamidine was well tolerated regardless of the dose used. Prophylaxis failures might be halved if the dose of aerosolized pentamidine were doubled. Compared with aerosolized pentamidine, oral regimens prevented 73% (95% confidence interval, 57% to 82%) of toxoplasmosis events by on-treatment analysis, but only 33% (95% confidence interval, 12% to 50%) by intention-to-treat. No significant difference in mortality was demonstrated between different regimens. CONCLUSIONS: Sulfamethoxazole-trimethoprim is the superior regimen, and low doses could improve tolerance without losing effectiveness for primary prophylaxis. Low doses of dapsone reduce toxic effects, but at the expense of some loss of efficacy. There are few data on the use of low-dose regimens for secondary prophylaxis. High doses of aerosolized pentamidine may improve the efficacy of this regimen. Aerosolized pentamidine is inadequate for prevention of toxoplasmosis, and strategies that improve the tolerance of oral regimens may increase effectiveness in preventing toxoplasmosis.

AIDS-Related Opportunistic Infections↗
PubMed1996

Uncertainty of the time of first significance in random effects cumulative meta-analysis.

We propose a process for evaluating quantities of clinical and statistical interest in cumulative meta-analysis. We use Monte Carlo simulation studies to assess the error variance of the time to significance in cumulative meta-analysis. For the specific cumulative meta-analyses that we simulated, the 95% confidence interval of the treatment effect, estimated by the random effects method at the time of earliest significance, appears to be approximately appropriate except when the hypothesized treatment effect is near the null. The Monte Carlo approach that we used can also estimate the power of a cumulative meta-analysis when two treatments differ in efficacy. We illustrate these issues in the context of five cumulative meta-analyses, each comparing two treatments for preventing mortality from myocardial infarction. These simulated meta-analyses demonstrate our main point, which is that the time of first significance, however parameterized, is itself a random variable with error variance.

Bias↗
PubMed1996

Gender-based mortality follow-up from the Program on the Surgical Control of the Hyperlipidemias (POSCH) and meta-analysis of lipid intervention trials. Women in POSCH and other lipid trials.

OBJECTIVE: The authors assessed the clinical results of lipid-lowering therapy in women. SUMMARY BACKGROUND DATA: The Program on the Surgical Control of the Hyperlipidemias (POSCH) has demonstrated that effective lowering of total cholesterol and low-density lipoprotein cholesterol in a postmyocardial infarction population significantly reduces atherosclerotic coronary heart disease (ACHD) mortality, ACHD mortality combined with a new confirmed nonfatal myocardial infarction, and the number of coronary artery bypass grafting and angioplasty procedures performed. METHODS: A review and meta-analysis were performed of the seven primary or secondary lipid/ atherosclerosis intervention trials-including POSCH-published in the English-language literature that included women and published results in women separate from the results in men or in the entire trial population. The main outcome measure analyzed was overall mortality. RESULTS: The Scottish Physicians Clofibrate Study, the Newcastle upon Tyne Clofibrate Study, and the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC I) Trial may have demonstrated a possible benefit in ACHD prognosis from effective lipid intervention in women. The other four available trials did not. The Minnesota Coronary Survey reported a 15.6% increase in overall mortality rate and a 30.6% increase in a combined cardiovascular endpoint rate in the lipid-intervention group. The Upjohn Colestipol Study demonstrated statistically significant reductions in overall and ACHD mortality in the men, but not in the women. The Scandinavian.

Cholesterol↗
PubMed1996

Predictive value of viral load measurements in asymptomatic untreated HIV-1 infection: a mathematical model.

OBJECTIVE: To model the predictive value of viral load measurements in asymptomatic patients with HIV-1 infection, who have CD4 cell counts > 500 x 10(6)/l and no prior antiretroviral therapy, when the time of seroconversion and the prior levels of viremia are unknown. DESIGN: A mathematical model was constructed for the changes in HIV RNA load over time based on data from cohorts of HIV-infected patients followed since the time of seroconversion. METHODS: For different values of viral load, the time to progression to AIDS or an equivalent state [progression to AIDS equivalent (PAE)] was calculated using a wide range of estimates for the time since seroconversion and the rate of change of the viral load over time. RESULTS: In the absence of antiretroviral treatment, patients with a viral load of 10(5) copies/ml serum are at risk for PAE in less than 3 years (0-3 years) and patients with a viral load half a log higher are at risk in less than 1 year. In contrast, patients with a viral load of 10(4.5) have at least 1.9 years and may have up to 8 years before risk of PAE. Patients with a viral load of 10(4) RNA copies/ml have at least 2.8 years and may have up to 19 years before risk of PAE. The rate of change of the viral load was an important predictor of outcome; the time since seroconversion had only a minor effect. CONCLUSIONS: The viral load in the plasma or serum has predictive value even if the time of seroconversion is unknown. The rate of change of viral load over time may also be an important predictive factor. Serial measurements of viral load over time may provide therapeutic guidance.

CD4 Lymphocyte Count↗
PubMed1996

Anthropometric measurements and body proportions among Chinese children.

There are significant racial differences in body proportions. Such data are not readily available for Chinese children. This article reports a cross section study of body proportions of 2193 Hong Kong Chinese children, ages 4 to 16 years, with equal gender distribution. Standing height, sitting height, and arm span were measured with standard equipment and methodology. Lower segment height was calculated as the difference between standing height and sitting height. Statistical analysis of the results showed a high linear correlation of the standing height with arm span, sitting height, and lower segment height, with a correlation coefficient ranging from 0.965 to 0.983 for both genders. When expressed as the ratio of standing height to arm span, the value was relatively constant and changed only linearly from 1.03 to 1 in girls and 1.03 to 0.98 in boys ages 4 to 16 years. The ratio of sitting height to lower segment height varied from a mean of 1.4 to 1.14 in boys and 1.36 to 1.18 in girls ages 4 to 16 years. The Chinese children were found to have a proportional limb segmental length relative to the trunk that differed significantly from the proportionally longer limbs in whites and blacks.

Adolescent↗
PubMed1996

An estimation of the functional disability burden in elderly Chinese age 70 years and over.

A cross-sectional survey of functional status among elderly Hong Kong Chinese aged 70 years and over was carried out to estimate the current burden of disability. Two thousand and thirty-two subjects (999 men, 1033 women) were recruited by random sampling of the old age and disability allowance schemes covering over 90% of the elderly population, stratified by sex and 5-year age groups. Functional ability was administered using the Barthel Index. The duration of disability, if any, was also noted. The prevalence of disability for different activities of daily living varied from 0.8% to 26% (lowest for feeding and highest for climbing stairs and bathing). The prevalence was higher for women than men, and higher in the older age group for both sexes. Men in the 80+ age group had shorter duration of disability compared with those in the 70-79 age group, and compared with women. Using disability years (estimated number of elderly with disability in the population x median duration of disability) as an estimate of disability burden, the number ranges from approximately 19,000 (inability to feed) to 100,000 (inability to climb stairs). This estimate may be useful in the planning of service provisions for the formal and informal care sector.

Activities of Daily Living↗
PubMed1995

The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature.

OBJECTIVE: To quantify the protective efficacy of influenza vaccine in elderly persons. DATA SOURCES: A MEDLINE search was done using the index terms influenza vaccine, vaccine efficacy, elderly, mortality, hospitalized, and pneumonia. Appropriate references in the initially selected articles were also reviewed. STUDY SELECTION: Only cohort observational studies with mortality assessment were included in the meta-analysis. In addition, 3 recent case-control studies, 2 cost-effectiveness studies, and 1 randomized, double-blind, placebo-controlled trial were reviewed. DATA EXTRACTION: Vaccine and epidemic virus strains, age and sex of patients, severity of illness, patient status, and study design were recorded. Upper respiratory illness, hospitalization, pneumonia, and mortality were used as outcome measures. DATA SYNTHESIS: In a meta-analysis of 20 cohort studies, the pooled estimates of vaccine efficacy (1-odds ratio) were 56% (95% Cl, 39% to 68%) for preventing respiratory illness, 53% (Cl, 35% to 66%) for preventing pneumonia, 50% (Cl, 28% to 65%) for preventing hospitalization, and 68% (Cl, 56% to 76%) for preventing death. Vaccine efficacy in the case-control studies ranged from 32% to 45% for preventing hospitalization for pneumonia, from 31% to 65% for preventing hospital deaths from pneumonia and influenza, from 43% to 50% for preventing hospital deaths from all respiratory conditions, and from 27% to 30% for preventing deaths from all causes. The randomized, double-blind, placebo-controlled trial showed a 50% or greater reduction in influenza-related illness. Recent cost-effectiveness studies confirm the efficacy of influenza vaccine in reducing influenza-related morbidity and mortality and show that vaccine provides important cost savings per year per vaccinated person. CONCLUSION: Despite the paucity of randomized trials, many studies confirm that influenza vaccine reduces the risks for pneumonia, hospitalization, and death in elderly persons during an influenza epidemic if the vaccine strain is identical or similar to the epidemic strain. Influenza immunization is an indispensable part of the care of persons 65 years of age and older. Annual vaccine administration requires the attention of all physicians and public health organizations.

Age Factors↗
PubMed1995

Early or deferred zidovudine therapy in HIV-infected patients without an AIDS-defining illness.

PURPOSE: To do a meta-analysis on the efficacy of early or deferred zidovudine monotherapy in patients with human immunodeficiency virus (HIV) infection but not the acquired immunodeficiency syndrome (AIDS). DATA SOURCES: Articles on zidovudine monotherapy published through May 1994. STUDY SELECTION: Double-blind, randomized, placebo-controlled trials addressing the efficacy of zidovudine monotherapy in HIV-infected persons without an AIDS-defining illness. DATA EXTRACTION: Progression to any primary trial end point; any clinical end point; and AIDS or death. Data were stratified according to disease stage at study entry and duration of follow-up (short-term, < 14 months; long-term, > 21 months). DATA SYNTHESIS: Early initiation of zidovudine therapy was of short-term benefit for all the end points evaluated (for example, the risk ratio for progression to any primary end point was 0.51; 95% CI, 0.41 to 0.64). Long-term trials showed a marginally significant trend of decreased progression to any primary end point (risk ratio, 0.73; CI, 0.52 to 1.03). The trend was not significant for other end points. With further stratification according to disease stage, progression to AIDS or death in the short term was significantly decreased for both symptomatic and asymptomatic patients with CD4 cell counts of less than 500 x 10(6)/L (risk ratios, 0.26 [CI, 0.13 to 0.56] and 0.43 [CI, 0.30 to 0.64], respectively). A regression analysis indicated a larger relative benefit in short-term trials and symptomatic patients than in long-term trials and asymptomatic patients. CONCLUSIONS: Early initiation of zidovudine therapy offers a benefit that decreases over time. Symptomatic patients experience a larger benefit than asymptomatic patients. The implications beyond 3 years of follow-up remain unknown.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Efficacy and safety of different aspirin dosages on vascular diseases in high-risk patients. A metaregression analysis.

PURPOSE: To compare the efficacy and safety of different aspirin dosages in trials with patients at increased risk of vascular disease. DATA SOURCES: Pertinent studies were selected using MEDLINE (1966 through 1992), weekly reviews of Current Contents (1970 through 1992), and references from review articles and editorials. STUDY SELECTION: Thirty-six randomized control trials of aspirin compared with another dosage of aspirin or with placebo. METHODS: The Mantel-Haenszel method of pooling odds ratios and metaregression involving log odds ratio (and the risk difference) on aspirin dosage, adjusting for the control rate and the mean length of follow up of the studies. RESULTS: For all patients and for subgroups of patients with previous vascular conditions, there was no relationship between dose and vascular events. For all patients, a dose-response relation was not found with gastrointestinal hemorrhages and hemorrhagic stroke, but was found with gastrointestinal symptoms and withdrawals from side effects. For every 25 mg/day increase in aspirin dosage, the odds ratio of gastrointestinal symptoms and withdrawals increased, respectively, by 0.87% (99% Cl, 0.18 to 1.57%) and 0.94% (99% Cl, 0.06 to 1.82%). The corresponding absolute risk increases were 0.58 and 0.78 per 1,000 patients. CONCLUSIONS: Direct and indirect comparisons of high-risk patients suggest no statistical differences in efficacy, gastrointestinal bleeds, and hemorrhagic strokes across aspirin dosages. These comparisons, however, suggest decreased risk of gastrointestinal symptoms and of withdrawals with lower doses of aspirin. More direct comparison studies are warranted that should contrast the benefits and risks to determine the net benefit.

Aspirin↗
PubMed1995

Determinants of bone mass in the Chinese old-old population.

One hundred and eighty-eight elderly men and women were included in a study of bone mass at the neck of femur and its related factors. The study subjects were a subsample of a Hong Kong wide study of the elderly population aged 70 years and above. The study variables included age, sex, body measurements of height, weight, body mass index, dietary calcium intake, grip strength, 16 feet (5 m) gait speed, smoking, drinking, and years since menopause among women. The neck of femur bone mineral density among elderly men was about 1 standard deviation higher than that of women. Subjects aged 85 years and above had about 20% lower bone mineral density at the neck of femur when compared with those in the age group 70-74 years. Mean dietary calcium intake ranged between 300 and 430 mg/day and was not associated with bone mass. Multiple regression analysis showed that body weight, 16 feet gait speed, sex and alcohol consumption explained 46% of the total variance of femoral neck bone mineral density. Body weight was the most significant predictor of bone mineral density, with a partial correlation coefficient of 0.5. The maintenance of body weight within the acceptable weight range and promotion of physical fitness may be important measures in reducing bone loss in the elderly population.

Aged↗
PubMed1995

Efficacy and safety of combined anticoagulant and antiplatelet therapy versus anticoagulant monotherapy after mechanical heart-valve replacement: a metaanalysis.

We performed a metaanalysis of five randomized controlled trials to compare the efficacy and safety of combined oral anticoagulant and antiplatelet therapy versus oral anticoagulants alone after prosthetic heart-valve replacement. The combined regimen reduced embolism and overall mortality by approximately 67% (pooled odds ratio [OR] 0.33; 95% confidence interval [CI] 0.16 to 0.69; p = 0.0032) and 40% (OR 0.60; 95% CI 0.32 to 1.12; p = 0.11), respectively, but increased the risk of hemorrhage by approximately 65% (OR 1.65; 95% CI 1.15 to 2.39; p = 0.0069) and of major gastrointestinal hemorrhage by approximately 250% (OR 3.47; 95% CI 1.43 to 8.40; p = 0.0058). It is estimated that for every 1.6 patients who had their stroke prevented by combination therapy, there was an excess of one major gastrointestinal bleed. This metaanalysis suggests that the benefits derived from the enhanced antithrombotic potential of combined therapy outweigh the toxic effects resulting from the enhanced anticoagulant potential of this regimen.

Administration, Oral↗
PubMed1995

Cumulative meta-analysis of clinical trials builds evidence for exemplary medical care.

Cumulative meta-analysis of clinical trials (a Bayesian interpretation for accumulating evidence) will profoundly affect medical care by summarizing evidence in the assessment of technology innovations. Application of the technique to the randomized control trials (RCTs) of streptokinase treatment of acute myocardial infarction, reduction of peri-operative mortality by antibiotic prophylaxis, and prevention of death from bleeding peptic ulcers has revealed efficacy years before it was suspected by any other means. Arrangement of the trials according to event rate in the controls, effect sizes, quality of the trials or according to covariables of interest has supplied unique information. If carried out prospectively the technique supplies invaluable information regarding indications for another trial, the number of patients necessary to determine the validity of past trends, and the type of patients who might be benefitted. Careful examination in a cumulative manner of the prior trials can reduce the need for future large trials.

Bayes Theorem↗
PubMed1995

The rational use of therapeutic drugs in the 21st century. Important lessons from cumulative meta-analyses of randomized control trials.

The use of randomized control trials to assess the usefulness of therapeutic drugs over the last half century has brought significant benefits to patient care. The full potential benefits, however, have been only partially fulfilled because available data are frequently poorly used. Meta-analysis has emerged as an important tool for combining clinical evidence. Several examples are presented that compared the results of cumulative meta-analysis of randomized control trials with clinical expert recommendations. These comparisons demonstrated that clinical expert recommendations are often not synchronized with accumulating evidence, and this lack of recognition often resulted in delays in the acceptance of effective drugs and the slow abandonment of possibly harmful therapeutic practices. The problems of inappropriate therapeutic drug use will only intensify as new drugs are introduced and new uses for established drugs are proposed. The rational use of therapeutic drugs can be achieved only through the routine use of meta-analysis on high-quality clinical data. Some suggestions are made to improve the quality of the original research and the ways of assembling meta-analyses and disseminating their results.

Diffusion of Innovation↗
PubMed1995

Effects of double-blind controlled calcium supplementation on calcium absorption in Chinese children measured with stable isotopes (42Ca and 44Ca).

A double-blind controlled Ca supplementation trial was conducted for 6 months in thirty-four 7-year-old Chinese children from Hongkong and Jiangmen, China. The children were randomly allocated to the study group (n 17) or control group (n 17), and a CaCO3 tablet (300 mg Ca) or a placebo tablet was taken daily. True fractional Ca absorption (TFCA) was evaluated before and after the trial using stable isotopes: 8 mg 44Ca mixed in 100 g chocolate milk was given after an intravenous injection of 0.75 mg 42Ca. There was no significant difference in baseline TFCA between the study group (60.6 (SD 11.4)%) and the controls (58.2 (SD 9.0)%; P = 0.55). Serum 25-hydroxycholecalciferol levels were comparable between the two groups (P = 0.71). After 6 months, TFCA of the study group (55.6 (SD 12.7)%) was significantly lower than that of the controls (64.3 (SD 10.7)%; P = 0.015). By comparing the individual changes in TFCA after the trial between the two groups there was a non-significant reduction in TFCA (5.03 (SD 12.4)%; P = 0.11, Wilcoxon signed-rank test) in the study group (60.6-55.6%), whereas a significant increase in TFCA (6.17 (SD 7.7)%; P = 0.004, Wilcoxon signed-rank test) was observed in the controls (58.2-64.3%). The differential in TFCA between the two groups after 6 months was significantly different (P = 0.001), and remained significant after adjustment for baseline dietary intakes, weight and height by multiple-regression analysis (P = 0.003). If the mechanism of TFCA from chocolate milk in response to the treatment effects is similar to that from the total diet, then our results suggest that children with adequate vitamin D status can adapt to a change in Ca intake by adjusting the efficiency of TFCA. In corollary, children on habitually-low Ca diets have a higher TFCA than the counterparts with higher Ca diets.

Calcium↗
PubMed1995

A randomized double-blind controlled calcium supplementation trial, and bone and height acquisition in children.

There is limited information relating Ca intake to bone and height acquisition among Oriental children who consume little or even no milk. The present controlled study investigated the acquisition of bone mass and height of Chinese children with an initial Ca intake of approximately 567 mg/d who were supplemented to about 800 mg/d. Eighty-four 7-year-old Hong Kong Chinese children underwent an 18-month randomized, double-blind, controlled Ca-supplementation trial. The children were randomized to receive either 300 mg elemental Ca or a placebo tablet daily. Bone mass of the distal one-third radius was measured by single-photon absorptiometry, lumbar spine and femoral neck were determined using dual-energy X-ray absorptiometry. Measurements were repeated 6-monthly. Baseline serum 25-hydroxycholecalciferol concentration and physical activity were also assessed. Baseline Ca intakes of the study group and controls were respectively 571 (SD 326) and 563 (SD 337) mg/d. There were no significant differences in baseline serum 25-hydroxycholecalciferol concentration (P = 0.71) and physical activity (P = 0.36) between the study and control groups. After 18 months the study group had significantly greater increases in lumbar-spinal bone mineral content (20.9 v. 16.34%; P = 0.035), lumbar-spinal area (11.16 v. 8.71%; P = 0.049), and a moderately greater increment in areal bone mineral density of the radius (7.74 v. 6.00%; P = 0.081) when compared with the controls. The results confirm a positive effect of Ca on bone mass of the spine and radius but no effects on femoral-neck and height increase. A longer trial is warranted to confirm a positive Ca effect during childhood that may modify future peak bone mass.

Absorptiometry, Photon↗