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.

Computed tomographic evaluation of the role of craniofacial and upper airway morphology in obstructive sleep apnea in Chinese.

OBJECTIVES: To evaluate the relationship between cephalometric parameters, upper airway morphological factors and obstructive sleep apnea (OSA) in Chinese subjects. DESIGN: Polysomnogram (PSG) were performed and scored using standard criteria. Supine lateral cephalometric parameters and pharyngeal cross-sectional areas at the level of velopharynx (VA) and hypopharynx (HA) were measured from computed tomographic scans. The roles of these parameters and other anthropometric/demographic characteristics in OSA (apnea hypopnea index, AHI > or = 5) and their relationship with severity of OSA were explored by multiple logistic and multinominal regression analysis. RESULTS: Ninety-two subjects, ranging from normal (n = 36), mild/moderate OSA (n = 34) to severe OSA (n = 22), were evaluated. Compared with normal subjects, OSA subjects were heavier (body mass index 27 vs. 24 kg/m2) and older (47 vs. 42 years of age); had smaller VA size and VA to HA ratio, lower positioned hyoid bone, longer and thicker soft palate, and more retropositioned mandible relative to maxilla. After controlling for body mass index and age, subjects with severe OSA (AHI > 30) had more retropositioned mandible relative to maxilla (odds ratio, OR 1.31, P = 0.044) and longer soft palate (OR 1.16, P = 0.01), while those with mild/moderate OSA had larger VA to HA ratio (OR 0.17, P = 0.018). CONCLUSIONS: Craniofacial factors and upper airway morphology contributed to severity of OSA in Chinese subjects. Having controlled for obesity, more retropositioned mandible was associated with more severe OSA.

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.

Angiotropic lymphoma occurring in a lacrimal sac oncocytoma.

This report describes a case of angiotropic variant of diffuse large B cell lymphoma within a benign oncocytoma of the lacrimal sac. The occurrence of this rare lymphoma within a benign neoplasm has not been documented previously. An 87 year old woman presented with a swelling over the area of the left lacrimal sac, which histological examination revealed to be an oncocytoma. Many small blood vessels within the tumour were filled with large cytologically atypical cells, which stained positively for leucocyte common antigen and a B cell antigen, CD20, confirming the presence of a large B cell non-Hodgkin's lymphoma of angiotropic type. Angiotropic lymphoma is a very rare and usually highly aggressive variant of non-Hodgkin's lymphoma, which classically involves the central nervous system and skin, but has been described within most organs. Its occurrence within a benign neoplasm is probably coincidental, although a close association between oncocytic epithelium and normal lymphoid cells is recognised in Warthin's tumour of salivary and lacrimal glands.

Sequential combination chemotherapy in patients with advanced nonsmall cell lung carcinoma: carboplatin and gemcitabine followed by paclitaxel.

BACKGROUND: The objective of this Phase II study was to evaluate the concept of sequential chemotherapy in the treatment of patients with advanced nonsmall cell lung carcinoma (NSCLC) by the administration of carboplatin plus gemcitabine followed by of paclitaxel. METHODS: Patients with Stage IIIB (pleural effusion) or Stage IV NSCLC and a Southwest Oncology Group (SWOG) performance status (PS) of 0--2 were eligible. Therapy consisted of three cycles of carboplatin (area under the concentration-time curve = 5.5 mg/mL per minute) on Day 1 and gemcitabine 1000 mg/m(2) on Days 1 and 8 every 21 days followed by three cycles of paclitaxel 225 mg/m(2) every 21 days. RESULTS: Of the 37 eligible patients, 81% had Stage IV disease, and 27% had a PS of 2; all were assessable for survival and toxicity; 32 patients were assessable for response. After treatment with carboplatin plus gemcitabine, there were no complete responses (CRs) and eight partial responses (PRs) (response rate [RR], 25%; 95% confidence interval [95% CI], 11--43%). The best overall response was two CRs and eight PRs (RR, 31%; 95% CI, 16--50%). The median survival time was 9.5 months, the 1-year survival rate was 36% (95% CI, 26--44%), the 2-year survival rate was 11% (95% CI, 3--25%), and the median time to disease progression was 4.9 months. The median survivals were 11.2 months for patients with a PS of 0--1 and 6.4 months for patients with a PS of 2. Noncumulative, reversible thrombocytopenia was the principal toxicity with carboplatin/gemcitabine therapy. Paclitaxel therapy was well tolerated, and moderate (Grade 3) neutropenia was the primary toxic effect. One cardiac death occurred, possibly related to paclitaxel. CONCLUSIONS: This study is the first to evaluate planned sequential chemotherapy in patients with NSCLC. Carboplatin plus gemcitabine followed by paclitaxel was well tolerated and resulted in promising survival in this patient population. This pilot experience forms the basis for an ongoing SWOG trial. Cancer 2001;92:146-52. Published 2001 American Cancer Society.

Increasing use of inhaled steroids associated with declining asthma mortality.

Increasing worldwide asthma prevalence and mortality has led to greater advocacy of inhaled agents, especially steroids. To determine whether corresponding drug usage trends had ensued locally, wholesale data (expressed as defined daily doses (DDDs)/1000 inhabitants/day) were compared for inclusive periods 1984-1986 and 1992-1994. Whereas absolute usage of anti-asthmatics increased by 79%, proportional inhaled usage increased markedly, especially of steroids (571%) and in hospitals. An odds ratio trend analysis revealed asthma mortality from 1992 onward had declined, particularly in males (p < 0.001). In Hong Kong, despite increasing asthma prevalence, more intensive use of anti-asthmatic drugs (especially inhaled steroids) was associated with declining asthma mortality.

An estimation of the post-mortem interval in human skeletal remains: a radionuclide and trace element approach.

Estimation of the post-mortem interval remains a contentious issue, with forensic pathologists often relying upon the recognition of morphological changes.A radionuclide approach has often been suggested in the literature, although limitations have prevented its application, most notably those of diagenesis. Within this pilot study, we show for the first time that there is a correlation between certain radionuclide content and time since death.A larger study is proposed to confirm these findings and possibly provide a calibration against which bones uncovered can be dated.

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.

Long-term culture of human immunodeficiency virus type 1 resulting in loss of glycosylation sites.

Cultures of human immunodeficiency virus type 1 (HIV-1) provided a model for the study of mutations in the absence of host antibodies. Replicate cultures of biological and molecular clones of HIV-1 were passaged weekly for 30 or 34 weeks. Eight regions of HIV-1 genomic RNA were analyzed by means of single-strand conformation polymorphism analysis and nucleotide sequencing. Six mutations were detected in the biological clones. Two were G-->A substitutions. The frequency of mutations was higher in V1 compared to that in other regions (P = 0.01). Three mutations involved loss of potential glycosylation sites in V1. These results show that mutations in the viral genome may result from selection by factors other than host immune pressures.

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.

An unusual case of pyrexia of unknown origin with cervical lymphadenopathy.

Kikuchi's disease is usually a self limiting illness characterised by pyrexia, neutropenia, and cervical lymphadenopathy particularly in young women of Asian descent. This often leads to an initial misdiagnosis of lymphoma. A case of a young Asian woman who presented with pyrexia of unknown origin is described.

The impact of chronic diseases on the health-related quality of life (HRQOL) of Chinese patients in primary care.

BACKGROUND: Ageing of the population results in an increasing number of people living with chronic diseases that can adversely affect their quality of life. Information on the impact of chronic diseases on quality of life can make health services more patient-centred. OBJECTIVES: The aim of this study was to determine the impact of eight chronic diseases on the health-related quality of life (HRQOL) of Chinese patients. METHODS: A cross-sectional case-control study was carried out on 760 adult Chinese patients of a family medicine clinic in Hong Kong. Each subject answered the COOP/WONCA charts and a standard questionnaire on demographic and morbidity data. The likelihood of sub-optimal COOP/WONCA scores of each disease group was compared with that of patients without any of the surveyed diseases. The independent effects of each disease on the COOP/WONCA scores were analysed by multivariate logistic regression, controlling for demographic variables and co-morbidity. RESULTS: Depression increased the risks for sub-optimal scores in all but one COOP/WONCA chart with odds ratios (OR) ranging from 2.1818 to 3.8645. Hypertension increased the risk of a sub-optimal physical fitness score (OR 1.7263). Increased risk of limitations in daily activities was associated with stroke (OR = 1.8771), osteoarthritis of the knee (OR = 1.5867), diseases of joints other than the knees (OR 2.0187) and asthma/COPD (OR 2.1679). Osteoarthritis of the knees also increased the risk of sub-optimal overall health (OR = 1.7927). CONCLUSIONS: Depression was the most disabling disease, and osteoarthritis of the knee had more impact on the HRQOL than many other chronic diseases. The lack of adverse effects of diabetes mellitus and heart disease on the HRQOL of Chinese patients deserves further studies.

Early detection of hepatocellular carcinoma increases the chance of treatment: Hong Kong experience.

The prognosis for patients with hepatocellular carcinoma (HCC) is poor because of the low chance of curative treatment. To increase the chance of intervention and to improve survival, early detection of subclinical HCC (SCHCC) by alpha-fetoprotein (AFP) and/or ultrasonography (USG) screening is implemented in many countries. Three hundred six Chinese patients with HCC diagnosed between January 1995 and December 1997 were recruited. They were categorized into two groups: 142 patients (group 1) had SCHCC diagnosed by screening (AFP and/or USG), and 164 patients (group 2) presented with symptomatic HCC. The tumor size was significantly smaller in group 1 compared with that of group 2 (3.5 cm vs. 8.1 cm; P <.0001). A significantly higher proportion of patients had bilobar involvement, multifocal HCC, diffuse-type HCC, portal vein infiltration, and distant metastasis in group 2 when compared with group 1. Operability and feasibility of treatment by transcatheter intra-arterial chemoembolization (TACE) in group 1 patients (26.8% and 45.1%, respectively) were significantly better than in group 2 patients (7.9% and 32.3%, P <.0001 and P =.03, respectively). The cumulative survival rate was significantly higher in group 1 than in group 2 (P <.0001). For those who had surgical resection and those who had TACE, group 1 patients had a higher cumulative survival rate compared with that of group 2 patients (P =.04 and P =.0003, respectively). Screening for HCC by AFP and/or USG can identify tumors at an early stage, resulting in a higher chance of receiving treatment. Whether it can improve survival requires a further prospective, randomized study.

Correlation of bone scintigraphy and histological findings in medial tibial syndrome.

OBJECTIVE: To correlate bone scintigraphy and histopathological findings in patients with medial tibial syndrome. METHODS: Twenty patients (32 limbs) with a clinical diagnosis of medial tibial syndrome had surgery. Bone scintigraphy before the operation was compared with the histological appearance of bone and periosteal specimens obtained at surgery. RESULTS: Delayed bone scintigraphy showed normal appearance in 11 limbs, characteristic diffuse tubular pattern uptake in 16 limbs, and focal uptake in five. Periosteal histology disclosed fibrous thickening as the most common finding associated with increased vascularity, occasionally with chronic inflammatory cell infiltration, haemosiderin, and acid mucopolysaccharide deposition. Loss of osteocytes was the main finding of bone histology associated with some enlargement of lacunae and lamellar structure disruption. A grading system was used to score normal and abnormal histological appearance. For analysis the findings were regrouped to provide tables using Fisher's exact test. There was no correlation between bone scintigraphy and the histology of bone and periosteum, but two interesting observations were noted. Those cases with periosteal thickening had mostly normal bone scan appearance (p = 0.0028). Those cases with low levels of osteocyte loss had mostly abnormal bone scintigraphy. CONCLUSION: Abnormal histological appearance of bone and periosteum is a feature of medial tibial syndrome. These histological findings show poor correlation with bone scintigraphy. The exact pathogenesis of this syndrome remains unclear.