Meta-analysis of large outcome trials of angiotensin receptor blockers in hypertension.

Angiotensin receptor blockers (ARBs), also known as sartans, block the activation of angiotensin type 1 receptors and have a recognised role in the treatment of heart failure and nephropathy. Since 2002, there have been three major outcome trials of ARBs in hypertension. We performed a meta-analysis to evaluate the impact of ARB on major outcomes. Randomised controlled trials of ARBs in hypertensive subjects with an average follow-up of at least 2 years and at least 100 major cardiovascular events were included. For each trial, the ARB used, number and characteristics of subjects, baseline and change in blood pressure, cardiovascular and noncardiovascular outcomes were recorded. Three trials involving 29 375 subjects were included in the meta-analysis. In Losartan Intervention For Endpoint (LIFE) and Study on Cognition and Prognosis in the Elderly (SCOPE) but not in Valsartan Antihypertensive Long-term Use Evaluation trial (VALUE), an ARB reduced the occurrence of the primary end point and stroke compared to control. Compared to other antihypertensive drugs, ARB treatment was associated with no significant change in all-cause mortality (relative risk ratio (RRR) 0.96, 95% CI: 0.88-1.06, P = 0.45). There was an increase in myocardial infarction (RRR, 1.12, 95% CI: 1.01-1.26, P = 0.041), but a decrease in new-onset diabetes mellitus (RRR, 0.80, 95% CI: 0.74-0.86, P < 0.0000001). In conclusion, the reduction in new-onset diabetes partly offsets any increase in the risk of myocardial infarction. Most hypertensive patients require more than one class of drugs. Small differences in treatment outcome should not over-ride the importance of good blood pressure control.

Lack of association between slow acetylator status and spontaneous lupus erythematosus.

The Chinese in Southeast Asia are recognized as a population group that has a relatively high prevalence of rapid "acetylators" and a relatively high incidence of systemic lupus erythematosus. This study was designed to evaluate the possibility that there were environmental lupus erythematosus provocative substances eliminated by acetylation that resulted in a preponderance of slow acetylators among patients with the disease. We compared acetylator status in 36 Chinese women with mild, stable, and confirmed lupus erythematosus and 36 healthy control subjects matched for age, sex, and ethnic origin. Acetylator status was determined by use of HPLC to assay 5-acetylamino-6-formylamino-3-methyluracil/methylxanthine (AFMU/MX) and AFMU/(AFMU + MX) ratios in urine 1 to 4 hours after drinking a strong cup of coffee (caffeine). By use of parametric and nonparametric methods of analysis, the frequency distribution of AFMU/MX and AFMU/(AFMU + MX) ratios in both the patients and control subjects were determined to be very similar. Thus there was no association between slow acetylator status and lupus erythematosus in the study subjects.

The hepatitis C virus genome: a guide to its conserved sequences and candidate epitopes.

A comprehensive analysis of reported hepatitis C virus genomic sequences comprising 151 partial or complete nucleotide sequences and 159 partial or complete amino acid sequences revealed an irregular composition of conserved and variable regions. There were but eight conserved nucleotide sequences, none outside the 5' noncoding and structural regions. A search among conserved amino acid sequences revealed 14 candidate B-cell epitopes, which were chosen mainly on the basis of their hydrophilicity profiles. Twenty five candidate T-cell epitopes were selected according to the criteria of absolute conservation of amino acid sequence, together with characteristic sequence motifs, amphipathic helical structure, or both. Conserved peptide sequences, with the characteristics of both B- and T-cell epitopes, were identified in the nonstructural 5 (NS5) region of the genome.

Kernel density analysis of variable and conserved regions of the envelope proteins of human immunodeficiency virus type 1 and associated epitopes.

A new statistical approach to the study of conservation of amino acid and nucleotide sequences based on kernel density analysis is described that enables analysis of both conserved and highly variable HIV-1 protein sequences. The amino acid sequences of HIV-1 env proteins in 63 isolates were analysed to determine, first, whether the designations of regions identified in 1987 as conserved (C1-C6) or variable (V1-V5) were still valid. Even though the data base used was nine times larger, the designations that were based on seven isolates from five patients remain correct. Second, the new approach enabled the quantifications of the degree of conservation in reported B or T cell epitopes. Using this approach, highly conserved epitopes located in both gp41 and gp120 were identified.

A community study of sleep-disordered breathing in middle-aged Chinese men in Hong Kong.

BACKGROUND: Sleep-disordered breathing (SDB) in Asian populations is being increasingly recognized. This study investigated the prevalence of SDB in Chinese middle-aged office-based male workers in Hong Kong. METHODS: Sleep questionnaires were distributed to 1,542 men (age range, 30 to 60 years), and 784 questionnaires were returned. Subsequently, full polysomnographic (PSG) examinations were conducted in 153 questionnaire respondents. Subjects with an apnea-hypopnea index (AHI) > or =5 were recalled for clinical assessment. RESULTS: Questionnaire respondents were similar in age and body mass index (BMI) to the general community in the target age range and gender. Habitual snoring was reported by 23% of this cohort and was associated with excessive daytime sleepiness (EDS), hypertension, witnessed abnormal breathing pattern, BMI, and leg movements during sleep. Allowing for subject bias in undergoing PSG, the estimated prevalence of SDB and obstructive sleep apnea syndrome (OSAS) (defined as SDB in the presence of EDS) at various AHI cutoff threshold values was 8.8% and 4.1% (AHI > or =5), 6.3% and 3.2% (AHI > or =10), and 5.3% and 3.1% (AHI > or =15). Multiple stepwise logistic regression analysis identified BMI, habitual snoring, time taken to fall asleep, and age as predictors of SDB at AHI > or =5. Analysis of anthropometric parameters indicated that the relative risk of OSAS attributable to obesity was less than in white subjects. CONCLUSION: This community-based study of sleep apnea among middle-aged men in Hong Kong using full PSG demonstrated an estimated prevalence of OSAS (AHI > or =5 and EDS) at 4.1%. Increasing BMI and age were associated with SDB, although factors other than adiposity may also have an important pathogenic role in OSA in Chinese subjects.

Histologic changes in Chinese patients with chronic hepatitis B virus infection after interferon-alpha therapy.

To evaluate the histologic effects of interferon-alpha (IFN alpha) therapy on chronic hepatitis B virus (HBV) infection, a semiquantitative study using a modified Knodell's numeric histologic scoring system was performed on paired pre- and post-treatment liver biopsy specimens from 127 adult Chinese patients from two trials of IFN alpha therapy (IFN alpha, n = 86; control, n = 41). The effects of IFN alpha therapy on the hepatic expression of HBV antigens were also determined using immunohistochemical analysis. Serologic response with clearance of HBV e antigen (n = 18) was associated with reduction in lobular activity, periportal piecemeal necrosis, portal inflammation, and total histologic scores. Loss of HBV e antigen also was associated with a reduction in the amount of HBV core antigen in the hepatocytes. In contrast, there was an increase in hepatic expression of HBV surface antigen after IFN alpha therapy. Patients who lost HBV e antigen with IFN alpha therapy were characterized by more severe initial periportal piecemeal necrosis before treatment. These data indicate that (1) serologic response is associated with a reduction in hepatic HBV replication and an improvement in hepatic histology, and (2) patients with severe periportal piecemeal necrosis respond more favorably to IFN alpha therapy.

Free perforation of gastric carcinoma. Results of surgical treatment.

OBJECTIVE: To define by actual standards the results of treatment of free perforation of gastric carcinoma in a consecutive number of patients treated at one institution. DESIGN: Case series of patients with perforated adenocarcinoma of the stomach treated in Hong Kong between 1984 and 1992. SETTING: Urban academic medical center. PATIENTS: Thirty-four Chinese patients who were operated on for perforated gastric carcinoma. A risk scoring system was used to predict postoperative mortality. Factors with a possible influence on postoperative mortality and long-term survival were studied using univariate and multivariate analysis. INTERVENTION: All patients underwent laparotomy, which was performed for closure of the perforation in four patients and for gastrectomy in 30. MAIN OUTCOME MEASURES: Thirty-day mortality and survival times. RESULTS: The 30-day mortality rate was 20%, and the median survival time was 10 months (range, 2 to 92 months). The risk score was the only significant predictor of 30-day mortality, and the pathologic TNM staging, of long-term survival. CONCLUSIONS: A significant proportion of patients can be saved and offered good palliation with emergency gastrectomy; those likely to die can be identified before surgery.

Prediction of persistent carbohydrate intolerance in patients with gestational diabetes.

A 12-month prospective study was carried out in 120 Chinese patients with gestational diabetes who were found to have persistent carbohydrate intolerance at 6 weeks postpartum. The 75 g OGTT and WHO diagnostic criteria were employed for both antepartum and postpartum assessment. By 12 months, persistent carbohydrate intolerance was found in 13.3% of the patients only, 6 patients were diabetic while 10 had impaired glucose tolerance. Of those whose carbohydrate tolerance reverted to normal, 85% did so within the first 6 months. The clinical variables were analysed by multiple discriminant analysis using the logistic model. Five prognostic variables which were predictive of persistent carbohydrate intolerance at 12 months were identified. In order of decreasing predictive value, these included a high fasting glucose during pregnancy and at the first postnatal visit, a high antepartum 2 h blood glucose, the requirement of insulin during pregnancy, and a high postpartum 2 h blood glucose. Macrosomia, gestational age at diagnosis and a family history of diabetes were not predictive of persistent carbohydrate intolerance. Multiparity, maternal age and body mass index were of marginal significance only. The fitted logistic model provides a mechanism to estimate the probability of persistent carbohydrate intolerance. Such information will be helpful in patient counselling and in the efficient planning of postpartum medical follow-up.

Self-medication among Hong Kong Chinese.

A randomized telephone survey on the practice of self-medication in the preceding 2 weeks was carried out from October 1989 to April 1990 among Chinese living in Hong Kong. 1068 people were interviewed. Self-medication was a common and universal practice by Hong Kong Chinese with a prevalence of 32.5% in 2 weeks. Those who reported illness were significantly more likely than those who did not use self-medication (65 vs 18.2%) and to have used more than one item of medications (39 vs 20%). Chinese tonics were the most frequently used self-medications although they were the least known. Chinese medicines were used as often as Western medicines in the self-treatment of illnesses. People used self-medication mainly because they felt that they knew what to do. About 80% of the Western and Chinese medicines were perceived to be effective but only 49% of the tonics were reported so. Side effects were reported from all types of medications with an overall prevalence of 6.4%. There was a lack of knowledge of the possible side effects in over 96% of the self-medications which is an area for patient education. The popularity but the relative lack of knowledge of Chinese tonics call for more scientific research and better regulation on their sales.

An evaluation of the prognostic factors in metastatic gestational trophoblastic disease.

A retrospective evaluation of prognostic factors in 55 patients suffering from metastatic gestational trophoblastic disease (MGTD) treated by modified Bagshawe's CHAMOCA regimen was done. The prognostic significance of the eight prognostic factors in the WHO scoring system, number of sites of metastasis and FIGO staging were evaluated by univariate analysis using Chi-square test with Yates' correction and odds ratio and by multivariate analysis using Cox proportional hazard analysis and logistic regression analysis. In the univariate analysis, the intervals between antecedent pregnancy and the diagnosis of GTD, (P = 0.004) the level of hCG (P = 0.02) and the number of metastatic sites (P = 0.046) were significantly associated with death. In the multivariate analysis, only the interval between the antecedent pregnancy and the diagnosis and the level of hCG were significantly associated with death. Thus, it seems that the interval between antecedant pregnancy and the diagnosis and the level of hCG were the two most significant factors in predicting mortality in high risk MGTD. The WHO staging was more predictive of poor outcome than that of the FIGO staging in this group of patients.

Long-term combination therapy with aspirin and clopidogrel.

The possible additive antiplatelet effects of aspirin and clopidogrel have been explored in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and Management of Atherothrombosis with Clopidogrel in High Risk Patients (MATCH) studies. To assess the overall absolute beneficial and/or harmful impact of aspirin and clopidogrel combination therapy compared with monotherapy with either drug, we analyzed the results from both trials in terms of number needed to treat per year. Treating between 35 and 204 at-risk patients for 1 year with combination therapy appeared to prevent 1 patient from experiencing an adverse primary cardiovascular outcome; whereas, about 1 in 63 such patients appeared liable to major bleeding during that period. We determined that the evidence to date indicates no overall advantage for combination therapy with anti-platelet drugs in preference to monotherapy.

Prognostic significance of serum tumour markers in carcinoma of the cervix.

PURPOSE: The purpose was to evaluate the prognostic significance of serum tumour markers and other potential prognostic factors in cervical cancer. MATERIALS AND METHODS: Five hundred and thirty-one patients with cervical cancer were studied. The pre-treatment levels of SCC (squamous cell carcinoma antigen), TPA (tissue polypeptide antigen), CEA (carcinoembryonic antigen), CA125 and hCG (human chorionic gonadotrophin) were assayed in these patients. Possible association between raised tumour markers and potential prognostic factors and their prognostic significance were sought by univariate and multivariate Cox analysis. RESULTS: SCC was raised in 65% of squamous cell carcinoma of the cervix and TPA was raised in 50%. Other markers were raised in less than 25%. No tumour markers were raised more than 30% in adenocarcinoma of the cervix. Raised SCC and TPA were related to advancing age, stage and grade of differentiation. Univariate analysis showed that age, stage, grade, raised SCC and TPA were significant prognostic factors on survival. Multivariate Cox analysis showed that stage was the most significant factor. CONCLUSION: Stage, age, grade of differentiation, raised pre-treatment levels of SCC and TPA were significant prognostic factors in cervical cancer using univariate analysis. However, only stage remains the most important independent prognostic factor in multivariate analysis. The prognostic value of these other factors in early stage disease needs further exploration.

Appraising published claims about drug treatment to implement best therapy in clinical practice.

The validity and applicability of publications about individual clinical studies and systematic overviews regarding interventions with drugs need to be established and perceived in quantitative terms to implement evidence-based, best current therapy. This requires an understanding of study design, various types of bias, intention to treat analysis, clinical versus statistical significance, and other considerations. The quantitative appreciation of drug effects may be facilitated by arranging results from case-control studies, cohort studies, and controlled trials in suitable contingency tables. Relative risks, relative risk reductions, odds ratios, and absolute risk reductions (in a given period of time), as well as corresponding numbers needing treatment (to prevent one event) may then be calculated. Systematic overviews of multiple clinical trials and assessment of their combined quantitative significance (meta-analyses) were developed to enhance statistical power, to enhance the level of confidence about small differences in effect, and to reconcile conflicting claims. The results of a meta-analysis are usually represented by so-called 'forest plots' of point estimates (corresponding to medians) and their respective confidence intervals, as well as a combined point estimate and confidence interval. Heterogeneity (important differences between findings from individual trials is a special problem incurred with this relatively new tool. The meta-analysis are also specially prone to other special sources of bias-a greater likelihood that trials reporting 'favourable' effects are published, covert duplicate inclusion of results from the same patients, and non-blinded meta-analysers.

Cost-effectiveness analysis of applying the Cholesterol and Recurrent Events (CARE) study protocol in Hong Kong.

OBJECTIVE: To determine the cost-effectiveness of secondary prevention with pravastatin in Hong Kong patients with coronary heart disease and average cholesterol levels. DESIGN: Cost-effectiveness analysis based on published results of the CARE study. PATIENTS: Men and women post-myocardial infarction with average cholesterol levels. MAIN OUTCOME MEASURES: Cost-effectiveness analysis: cost per life saved, cost per fatal or non-fatal coronary event prevented, cost per procedure prevented, and cost per fatal or non-fatal stroke prevented. Cost-utility analysis: gross cost and net cost per quality-adjusted life year gained calculated using two alternative models. RESULTS: Cost per life saved or death prevented was HK$4,442,350 (non-discounted); cost per fatal or non-fatal cardiac event prevented HK$1,146,413; cost per procedure prevented HK$732,759; and cost per fatal or non-fatal stroke prevented HK$2,961,566. Net cost per quality adjusted life year gained was HK$73,218 and HK$65,280 non-discounted, respectively using the two alternative models. CONCLUSIONS: The results of this study can assist in prioritising the use of health care resources in Hong Kong but should be considered alongside the benefits and costs of alternative interventions for coronary heart disease.

Tracing quantitative measurements on human chromosomes in family studies.

Statistical methods are developed for tracing quantitative measurements on human chromosomes from parents to offspring. Tests for transmission are briefly considered.

Bone mass in men with Klinefelter's syndrome and in normal subjects, estimated by the cortical thickness of bone.

Metacarpal cortical thickness has been measured in a sample of 47,XXY men and two control samples of 46,XY men and 46,XX women in the age range 20-70. The results suggest that in this age range cortical thickness in 47,XXY men is more similar to that of normal women than normal men.

Longitudinal study of heart size in older people.

Transverse cardiac diameter and transverse thoracic diameter were measured in a longitudinal study of older men and women at the original examination and after five years. The cardiothoracic ratio overestimated 5-year changes in heart size, because of significant decreases with age in transverse thoracic diameter. A regression equation to predict transverse cardiac diameter from age and weight had been previously computed from the data obtained at the initial examination. This was a satisfactory predictor of recorded 5-year changes except in women of 70 years and over at entry to the study in whom the predicted change was significantly larger than the recorded change. This had resulted from the death during the 5 years of women in that age group with larger transverse cardiac diameters.