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Biomedical subjects

J Lau

Publications and source records attributed to J Lau.

At least 145 records · Page 8Linked to original sources
PubMed1997

Predictors and impact of patients lost to follow-up in a long-term randomized trial of immediate versus deferred antiretroviral treatment.

We studied predictors for losses to follow-up and the impact of such losses in the AIDS Clinical Trials Group 019 protocol, a long-term randomized trial of immediate versus deferred antiretroviral therapy in asymptomatic HIV-1-infected patients with >500 CD4 cells/mm3. The trial was selected because of its key importance in determining guidelines for antiretroviral therapy, and because it had the longest follow-up among all antiretroviral trials and the largest percentage of patients whose vital status was unknown at study end. Younger age, a history of parenteral drug use, and nonwhite race were associated with higher rates of loss to follow-up, but race was not an important predictor after adjusting for clinical site. There was large and statistically significant variability in the rates of losses among different clinical sites (p < 0.001). Patient retention was significantly better in clinical sites that enrolled many participants, with 25% of enrollees lost to follow-up in sites enrolling >100 patients and 44% in sites enrolling <33 patients each. As a group, patients lost to follow-up after the 2nd year had steeper declines of CD4 cell counts, and a significantly larger proportion had reached a CD4 cell count <300/mm3 in the year before being lost, compared with patients remaining in the study. Losses to follow-up probably decreased substantially the observed number of primary endpoints, curtailed the power of the trial to demonstrate any difference between immediate and deferred initiation of antiretroviral therapy, and may have introduced large bias in the estimated hazard ratio for the primary endpoint and its statistical significance.

Adult↗
PubMed1997

Effect of angiotensin-converting enzyme inhibitors on the progression of nondiabetic renal disease: a meta-analysis of randomized trials. Angiotensin-Converting-Enzyme Inhibition and Progressive Renal Disease Study Group.

BACKGROUND: The effect of angiotensin-converting enzyme (ACE) inhibitors in slowing the decline in renal function in nondiabetic renal disease varies among studies. PURPOSE: To use meta-analysis to assess the effect of ACE inhibitors on the development of end-stage renal disease caused by factors other than diabetes. DATA SOURCES: The English-language medical literature, identified by a MEDLINE search and unpublished studies. STUDY SELECTION: All randomized studies that compared ACE inhibitors with other antihypertensive agents and had at least 1 year of planned follow-up were selected. Studies of diabetic renal disease and renal transplants were excluded. A total of 1594 patients in 10 studies was included. DATA EXTRACTION: Data on end-stage renal disease, death, drop out, and blood pressure were extracted. Study investigators confirmed results and provided additional data. DATA SYNTHESIS: Among 806 patients receiving ACE inhibitors, 52 (6.4%) developed end-stage renal disease and 17 (2.1%) died; in the 788 controls, the respective values were 72 (9.1%) and 12 (1.5%). The pooled relative risks were 0.70 (95% CI, 0.51 to 0.97) for end-stage renal disease and 1.24 (CI, 0.55 to 2.83) for death; the studies were not significantly heterogeneous. The decreases in weighted mean systolic and diastolic blood pressures during follow-up were 4.9 and 1.2 mm Hg greater, respectively, in the patients who received ACE inhibitors. CONCLUSIONS: Angiotensin-converting enzyme inhibitors are more effective than other antihypertensive agents in reducing the development of end-stage nondiabetic renal disease, and they do not increase mortality. It could not be determined whether this beneficial effect is due to the greater decline in blood pressure or to other effects of ACE inhibition.

Adult↗
PubMed1997

Echocardiographic evaluation of cardiac function in paediatric oncology patients treated with or without anthracycline.

Using Doppler echocardiography, we studied the left ventricular systolic and diastolic function in 124 healthy control children (group C), 110 oncology patients who had received anthracycline (group A), and 76 oncology patients who had received chemotherapy not including anthracycline (group N), at rest and after supine bicycle exercise. The mean dosage of anthracycline that group A patients received was 219 +/- 95 mg/m2. Impaired systolic function was detected in 29% of the patients in group A and 4% in group N. Figures for impaired diastolic function for group A and N were 27% and 28% respectively. Abnormal diastolic function was detected more frequently in the first two years after chemotherapy in both groups. Four parameters measured at rest appeared to be specifically abnormal in group A but not in group N. These were ejection fraction, fractional shortening, rate-corrected velocity of circumferential fiber shortening (VCFC) and left ventricle peak systolic wall stress (LVWS). After exercise more parameters were abnormal in group N patients when compared to normal children, but abnormalities of VCFC and LVWS remained specific for group A. In conclusion, abnormalities of diastolic function were common among paediatric oncology patients no matter whether they had received anthracycline treatment or not. Abnormalities of systolic function were more specific to anthracycline toxicity. VCFC and LVWS were the most sensitive measurements for differentiating group N patients from group A patients.

Adolescent↗
PubMed1997

Correlation of biochemical response to interferon alfa with histological improvement in hepatitis C: a meta-analysis of diagnostic test characteristics.

The current goal of interferon treatment for chronic hepatitis C is to normalize alanine aminotransferase (ALT) and to eradicate detectable viral RNA. Many patients do not achieve this objective during treatment, and most do not sustain these outcomes after interferon is discontinued. However, biochemical or virological responses to interferon may not reflect accurately the histological consequences of therapy. The aim of this study was to determine the extent to which the biochemical measures reflect the histological outcomes in the treatment of hepatitis C with interferon alfa using a meta-analysis of diagnostic test characteristics. The data sources were English and non-English language studies retrieved from Medline (from 1966 to December 1995). The study selection included studies in which interferon alfa was used for treatment of chronic hepatitis C with liver biopsies performed before and after therapy. Data on histological and biochemical outcomes were extracted independently by two reviewers. Two separate criteria were used for defining histological response. When strict definitions of histological improvement were considered, histology improved in 28% (95% confidence interval [95% CI], 17%-43%) of patients after interferon treatment. The sensitivity and specificity of the ALT for determining histological change were 70% (95% CI, 56%-81%) and 66% (95% CI, 56%-75%), respectively. As many as 17% (95% CI, 9%-30%) of subjects with an abnormal ALT at the end of therapy may have improved histologically after interferon therapy. When less stringent definitions of histological improvement were considered, 62% (95% CI, 51%-72%) improved after therapy. The sensitivity and specificity of the ALT for determining histological change were 55% (95% CI, 44%-65%) and 75% (95% CI, 67%-81%), respectively. As many as 51% (95% CI, 38%-64%) may have improved, despite failure to normalize ALT. A substantial number of patients may improve histologically after interferon therapy. The significance of histological changes observed after interferon therapy must be weighed against the limitations of liver biopsy and the uncertain natural history of hepatitis C. Nevertheless, the ALT does not always reflect liver histology accurately after interferon alfa treatment and may underestimate histological improvement.

Alanine Transaminase↗
PubMed1997

The relationship between study design, results, and reporting of randomized clinical trials of HIV infection.

We examined whether the study design of randomized clinical trials for medications against human immunodeficiency virus (HIV) may affect the results and whether the outcomes of these trials affect reporting and publication. We used a database of 71 published randomized HIV-related drug efficacy trials and considered the following study design factors: endpoint definition and method of analysis, masked design, sample size, and duration of follow-up. Large variation was noted in the methods of analysis for surrogate endpoints. Often statistical significance for a surrogate endpoint was not associated with statistical significance for the clinical endpoint or for survival in the same trial, although disagreements in the direction of the treatment effect for surrogate endpoints and survival within individual trials were uncommon. Open-label design seemed to affect the magnitude of the treatment effect for two treatments. The magnitude of the treatment effect in trials of zidovudine monotherapy was inversely related to their sample size, but this probably reflected the confounding effect of longer duration of follow-up in large trials (with a resulting loss of efficacy) rather than publication bias. There was, however, evidence for potential bias in reporting and publication of HIV-related trials. Meta-analyses of published trials for specific treatments demonstrated a sizable treatment benefit for all the examined medications regardless of whether these medications were officially approved, controversial, or abandoned, raising concerns about either publication bias or unjustifiable rejection of potentially useful medications. Compared with trials published in specialized journals, trials published in journals of wide readership were larger (p = 0.001) and 4.4 times more likely to report "positive" results (p = 0.01). We identified several examples of trials with "negative" results that have remained unpublished for a long time. In conclusion, study design factors may have an impact on the magnitude and significance of the treatment effect in HIV-related trials. Bias in reporting can further affect the information that these studies provide.

Anti-HIV Agents↗
PubMed1997

Combining single patient (N-of-1) trials to estimate population treatment effects and to evaluate individual patient responses to treatment.

When treating individual patients, physicians may face difficulties using the evidence from center-based randomized control trials (RCTs) due to limitations in these studies generalizability. Therefore, they often perform their own "informal" tests of treatment effectiveness. Single patient ("N-of-1") trials provide a structured design for more rigorous assessment of medical treatments of chronic diseases, but are applied only to the index patient. We present a hierarchical Bayesian random effects model to combine N-of-1 studies to obtain an estimate of treatment effectiveness for the population and to use this population information to aid in the evaluation of an individual patient's trial results. The model's treatment effect estimates are adjustments between the population estimate and the individual's observed results. This adjustment is based upon the within-patient and between-patient heterogeneity. We demonstrate this patient-focused method using published data from 23 N-of-1 trial results comparing amitriptyline and placebo for the treatment of fibromyalgia.

Amitriptyline↗
PubMed1997

The impact of high-risk patients on the results of clinical trials.

The results of clinical trials may not reflect equally the experiences of all their individual participants. By modeling populations where patients have very diverse baseline risks of suffering an event of interest, it can be seen that very sick patients of high risk become the major determinants of how many events occur in the whole population, even though they may represent only a small minority. Human immunodeficiency virus-related trials and trials of magnesium in acute myocardial infarction are analyzed. When the benefit or toxicity from a treatment varies with the baseline risk of each patient, the treatment effect may be markedly different in populations with a different representation of high- and low-risk patients. The results of small clinical trials studying heterogeneous populations with binary outcomes depend on the sampling and outcomes of very few high risk participants. Conversely, mega-trials studying homogeneous populations would miss subgroups or individuals with diverse treatment responses. In both cases, aggregate trial results may be misleading for the care of many individuals.

Data Interpretation, Statistical↗
PubMed1997

An estimate of chronic disease burden and some economic consequences among the elderly Hong Kong population.

OBJECTIVES: To estimate the burden of chronic disease for an elderly Chinese population aged 70 years and over, and to illustrate the use of this information in estimating the economic consequences of disease burden using stroke as an example. PARTICIPANTS: A total of 1902 subjects recruited by random sampling of the old age and disability allowance schemes, which cover over 90% of the Hong Kong elderly population, stratified by sex and five year age groups from age 70 years onwards. METHOD: Information was collected on 10 medical conditions at baseline: arthritis, hypertension, cardiac disease, stroke, chronic obstructive airways disease, peptic ulcer, diabetes mellitus, osteoporotic fracture, malignancy, and dementia. A follow up survey was carried out after 18 months to determine the occurrence of new disease and the number with disease who had died. Disease burden is calculated as the number with disease at baseline plus the number developing new disease minus the number who had died. RESULTS: Disease burden figures were highest for arthritis, hypertension, cardiac disease, and peptic ulcer, and were higher in the 70-79 age group than the 80+ age group for some diseases. For stroke, the economic cost based on a population projection for 2001 was estimated to be around HK$1,900,000,000, or US$250 million. CONCLUSION: Information on the burden of chronic disease is important. It enables the economic consequences to be estimated so that strategies can be developed to prevent diseases with high costs and known effective preventive methods.

Age Distribution↗
PubMed1997

Prevalence of asthma and allergy in Hong Kong schoolchildren: an ISAAC study.

Asthma and allergic disease in children is increasing in many Western countries but such trend has not been well-defined in Chinese populations. This paper aims to determine the prevalence of asthma and allergic disease in Hong Kong schoolchildren and compare it with previous data to identify a changing trend. We studied 4,665 schoolchildren aged 13-14 yrs using the International Study of Asthma and Allergy in Childhood (ISAAC) protocol to determine prevalence rates for asthma, wheeze, respiratory symptoms, rhinitis and eczema in 1994-1995. Additional questions on education levels of the parents and smoking status were also asked. Concordance between responses to the written and video questionnaires was good (76% for wheeze ever, 80% for current wheeze). Prevalence rates for asthma ever, wheeze ever, and current wheeze were 11, 20 and 12%, respectively, and were greater in boys (p < 0.05). Rhinitis affected slightly over half of the subjects (52%), and eczema was reported by a sixth (15%), whilst current rhinitis and current eczema were present in 44% and 3.6% of children, respectively. In multiple logistic regression: odds ratio male sex (OR) 1.47; (95% confidence interval (95% CI) 1.15-1.86); current rhinitis (OR 3.00; 95% CI 2.36-3.81); current eczema (OR 2.34; 95% CI 1.40-3.93); and active smoking (OR 2.00; 95% CI 1.38-2.89) were associated with current wheeze; whilst severe wheezing attack was associated with: current rhinitis (OR 2.72; 95% CI 1.47-5.02); current eczema (OR 6.13; 95% CI 2.82-13.33); and active smoking (OR 4.62; 95% CI 2.43-8.76). Age, parental education and passive smoking were not important factors. When compared to previous epidemiological data obtained in 1992, the prevalence rates for asthma ever and wheeze ever had increased by 71 and 255%, respectively, in Hong Kong schoolchildren. The severity of asthma and respiratory symptoms showed a similar increasing trend. Further studies should aim to identify the role of the environment in the pathogenesis of asthma.

Adolescent↗
PubMed1997

Determinants of peak bone mass in Chinese women aged 21-40 years. III. Physical activity and bone mineral density.

Previous studies on the relation between moderate physical activity and bone mass have observed conflicting results. Many of these studies have not dissociated the role of physical activity by age groups and in relation to the period of peak bone mass formation. Our cross-sectional analysis of the baseline data of a longitudinal study of 273 women aged 21-40 attempted to evaluate the role of moderate physical activity on bone mass around the period of peak bone mass attainment. The analyses were carried out separately for the two age groups--21-30 and 31-40--and had also taken into account the effects of age, dietary calcium intake, and lean body mass on bone mineral density (BMD). The total metabolic equivalent values (MET) of leisure time physical activity was based on the MET values for each activity and the reported time spent on each activity in the past year. The results indicated that among the younger group of women, high level of leisure time physical activity was associated with higher bone mass at both the spine and the hip. Additive effects of physical activity and dietary calcium intake on the spine and the hip BMD were observed. Together with age and lean body mass, physical activity and dietary calcium intake accounted for 19% of the variances of bone mineral at the spine and 9-11% at the hip. Among women aged 31-40, presumably after the peak bone mass formation, lean body mass as well as fat mass have independent strong association with BMD. Physical activity was not associated with bone mass in this age group.

Absorptiometry, Photon↗
PubMed1997

Comparison of the ISAAC video questionnaire (AVQ3.0) with the ISAAC written questionnaire for estimating asthma associated with bronchial hyperreactivity.

BACKGROUND: A standardized protocol is essential for international comparisons of asthma prevalence and severity. The International Study of Asthma and Allergies in Childhood (ISAAC) used a standardized written questionnaire (WQ) and a video questionnaire (AVQ3.0) to survey the prevalence and severity of asthma in 13-14-year-old schoolchildren in different countries. OBJECTIVE: To compare the effectiveness of WQ and AVQ3.0 in predicting bronchial hyperresponsiveness (BHR), defined as having a provocation dose of inhaled methacholine causing a 20% fall in baseline FEV1 of 7.8 mumol. METHODS: One hundred and eighty-nine Chinese schoolchildren completed a written questionnaire followed by a video questionnaire on asthma symptoms. They then underwent bronchial challenge to methacholine. RESULTS: Fair correlations were seen between the first two corresponding questions (moderate wheezing at rest and exercise wheeze) in the two questionnaires with Kapper indices of 0.44 and 0.43, respectively. The ability to predict BHR, as indicated by the Youden's index, was similar between the corresponding questions of the two questionnaires, except for 'severe wheeze' which had a significantly higher Youden's index in AVQ3.0 (0.44) than the corresponding question in WQ (0.11, P < 0.05). CONCLUSION: The ISAAC International video questionnaire is at least as effective as the ISAAC written questionnaire in predicting BHR. It therefore provides a simple and valid tool for international comparisons of asthma prevalence and severity.

Adolescent↗
PubMed1996

Impact of epidemic and individual heterogeneity on the population distribution of disease progression rates. An example from patient populations in trials of human immunodeficiency virus infection.

Patients at the same stage of chronic disease may have had different rates of disease progression. The authors developed a mathematical modeling approach that allows reconstructing and comparing populations in terms of the disease progression rates of their participants when the disease onset and progression rates are unknown for individual patients. Human immunodeficiency virus 1 infection was used as an example. Both published and hypothetical models were used to describe the human immunodeficiency virus 1 epidemic (epidemic heterogeneity) and incubation and survival functions for different disease stages (individual heterogeneity). Reconstructions of populations with late disease (e.g., acquired immunodeficiency syndrome patients) show a marked predominance of rapid progressors, unless the incidence of new infections has been decreasing for a long time. Rapid progressors would also predominate in populations of acute seroconverters, unless diagnosis is based on repeated serologic screening rather than symptoms. Populations of patients who have not progressed beyond an early stage of the disease (e.g., patients with CD4 cell counts > 500/microliter) tend to overrepresent slow progressors, especially if the epidemic has been decreasing for a long time. With this approach, one can assess whether the target population of a clinical trial is comparable with other patient populations at different places and times. Epidemic and individual diversity may even affect trial results if patients with different progression rates experience different benefits from a treatment. By modeling the targeted populations in trials of early versus deferred antiretroviral treatment, the authors observed larger treatment benefits in trials in which rapid progressors probably predominated, compared with trials of slow progressors.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Changes in clinical trials mandated by the advent of meta-analysis.

Service on the Data Monitoring Committee of the CPEP (Calcium for Pre-eclampsia Prevention) has led us to four conclusions about clinical trials which we should like to present to this gathering of biostatisticians for their reactions: (i) meta-analyses of the pertinent published trials of the same therapy should always be undertaken before the start of a new trial, and the results examined to help determine the design of a new trial or determine if a trial should be undertaken at all; (ii) assuming that a decision is made to go ahead, the results of the past trials should be used in sizing the new one; (iii) in the course of the new one, regardless of the size estimates, stopping early should be considered if the trends conform to the results of the meta-analysis; and (iv) heterogeneity of patients entering clinical trials is desirable and should be specifically studied, and it should never be concluded that an average outcome is applicable to all future patients.

Calcium↗
PubMed1996

The effect of dietary protein restriction on the progression of diabetic and nondiabetic renal diseases: a meta-analysis.

BACKGROUND: Dietary protein has long been thought to play a role in the progression of chronic renal disease, but clinical trials to date have not consistently shown that dietary protein restriction is beneficial. PURPOSE: To use meta-analysis to assess the efficacy of dietary protein restriction in previously published studies of diabetic and nondiabetic renal diseases, including the recently completed Modification of Diet in Renal Disease Study. DATA SOURCES: The English-language medical literature published from January 1966 through December 1994 was searched for studies examining the effect of low-protein diets in humans with chronic renal disease. A total of 1413 patients in five studies on nondiabetic renal disease (mean length of follow-up, 18 to 36 months) and 108 patients in five studies of type I diabetes mellitus (mean length of follow-up, 9 to 35 months) were included. STUDY SELECTION: Randomized, controlled studies were selected for nondiabetic renal disease; randomized, controlled studies or time-controlled studies with nonrandomized crossover design were selected for diabetic nephropathy. DATA EXTRACTION: Data in tables, figures, or text were independently extracted by two of the authors. DATA SYNTHESIS: The relative risk for progression of renal disease in patients receiving a low-protein diet compared with patients receiving a usual-protein diet was calculated by using a random-effects model. In five studies of nondiabetic renal disease, a low-protein diet significantly reduced the risk for renal failure or death (relative risk, 0.67 [95% Cl, 0.50 to 0.89]). In five studies of insulin-dependent diabetes mellitus, a low-protein diet significantly slowed the increase in urinary albumin level or the decline in glomerular filtration rate or creatinine clearance (relative risk, 0.56 [Cl, 0.40 to 0.77]). Tests for heterogeneity showed no significant differences in relative risk among studies of either diabetic or nondiabetic renal disease. No significant differences were seen between diet groups in pooled mean arterial blood pressure (diabetic and nondiabetic patients) or glycosylated hemoglobin level (diabetic patients only). CONCLUSION: Dietary protein restriction effectively slows the progression of both diabetic and nondiabetic renal diseases.

Adult↗