The risk of tuberculosis in SLE patients from an Asian tertiary hospital.

Systemic lupus erythematosus (SLE) has been associated with increased risk of tuberculosis (TB). However, little is known about the extent and risk factors for TB among Asian patient with SLE. We aimed to assess the rate of TB in patients with SLE, and investigate the risk of SLE on TB development using hospital administrative database. This is an historical cohort study of hospital discharge database from 2004 to 2011 to identify cases with SLE and TB using International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Australian Modification (ICD-9-AM) codes. Of 301568 hospitalized patients, 841 (0.3%) patients had SLE, 1843 (0.6%) patients had TB, including 17 SLE patients (2.0%). SLE patients had a significantly higher rate of TB (2.0 vs. 0.6%, p < 0.001) compared to that of patients without SLE. The differences in the higher rate after breaking down was in the pulmonary TB group (1.7 vs. 0.5%, p < 0.00) but not in extrapulmonary TB group (0.4 vs. 0.1%, p = 0.060). Logistic regression analyses showed that SLE was a significant and independent predictor of TB (odds ratio 4.6, 95% CI 2.8-7.5, p < 0.001) after adjustment for factors such as age group, gender, ethnicity, admission class, nutritional deficiency, organ transplantation, and Charlson comorbidity index. SLE patients were found to experience higher rates of tuberculosis in this group of Asian patient population. Patients with SLE should be considered as a high-risk group for TB, active screening for latent patients and treatment for positive TB patients is needed.

Berberine-induced haemolysis revisited: safety of Rhizoma coptidis and Cortex phellodendri in chronic haematological diseases.

Two commonly used berberine-containing Chinese herbs, Rhizoma coptidis (RC) and Cortex phellodendri (CP), have been banned in Singapore for the past three decades due to implication of berberine in aggravating jaundice and kernicterus in neonates with glucose-6-phosphate dehydrogenase deficiency. Here we conducted a single arm, phase I/II clinical study on Chinese herbal medicine for patients with chronic cytopenic haematological conditions and we analysed a subset of 20 patients who also had RC, CP or both in their herbal concoction. We found no organ toxicity or electrolyte imbalance in these 20 patients where RC was administered for 1055 patient-days and CP for 1252 patient-days. In three patients with thalassemia intermedia, transient elevation in serum bilirubin level was observed but this was not associated with any aggravation of anaemia or liver dysfunction. A review of the literature found conflicting evidence of varying levels either supporting or refuting the allegation of neonatal jaundice and kernicterus caused by berberine. There were, however, very few clinical reports of adverse reaction attributable to RC or CP in oral TCM concoction. We conclude that based on traditional dosage and indication, the use of RC and CP in oral concoction is safe.

Prognostic factors for mortality due to pneumonia among adults from different age groups in Singapore and mortality predictions based on PSI and CURB-65.

INTRODUCTION: Pneumonia is associated with considerable mortality. However, there is limited information on age-specific prognostic factors for death from pneumonia. METHODS: Patients hospitalised with a diagnosis of pneumonia through the emergency department were stratified into three age groups: 18-64 years, 65-84 years and ≥ 85 years. Multivariate logistic regression and receiver operating characteristic curve analyses were conducted to evaluate prognostic factors for mortality and the performance of pneumonia severity scoring tools for mortality prediction. RESULTS: A total of 1,902 patients were enrolled (18-64 years: 614 [32.3%]; 65-84 years: 944 [49.6%]; ≥ 85 years: 344 [18.1%]). Mortality rates increased with age (18-64 years: 7.3%; 65-84 years: 16.1%; ≥ 85 years: 29.7%; p < 0.001). Malignancy and tachycardia were prognostic of mortality among patients aged 18-64 years. Male gender, malignancy, congestive heart failure and eight other parameters reflecting acute disease severity were associated with mortality among patients aged 65-84 years. For patients aged ≥ 85 years, altered mental status, tachycardia, blood urea nitrogen, hypoxaemia, arterial pH and pleural effusion were significantly predictive of mortality. The Pneumonia Severity Index (PSI) was more sensitive than CURB-65 (confusion, uraemia, respiratory rate ≥ 30 per minute, low blood pressure, age ≥ 65 years) for mortality prediction across all age groups. CONCLUSION: The predictive effect of prognostic factors for mortality varied among patients with pneumonia from the different age groups. PSI performed significantly better than CURB-65 for mortality prediction, but its discriminative power decreased with advancing age.

Simple clinical prognostic model for hepatocellular carcinoma in developing countries and its validation.

PURPOSE: More than 80% of hepatocellular carcinomas (HCCs) worldwide occur in developing countries, especially in Asia. It often presents at an advanced stage beyond treatment. In this circumstance, a simple prognostic model is useful. Previous prognostic models require radiologic and laboratory investigations that are not readily available in developing countries. Our aim is to formulate and then validate a simple clinical prognostic model for HCC in an Asian population using only clinical parameters and with serum alpha-fetoprotein (AFP) as the sole laboratory test. PATIENTS AND METHODS: Cox regression modeling was performed on several clinical parameters and serum AFP level in 397 patients with HCC who received only supportive care in Singapore. A later group of 324 HCC patients from an Asia-Pacific-wide randomized trial was then used to validate the model. RESULTS: Ascites, physical performance status, and serum AFP were independently predictive of survival. Cox analysis yielded a simple score based on these three variables that categorizes patients into low-, medium-, and high-risk groups with 6-month survivals of 43%, 21%, and 5%, respectively. The prospective validation data provided corresponding estimates of 33%, 15%, and 3% and give confirmation of the utility of the simple model. CONCLUSION: We have formulated and prospectively validated a simple prognostic score for untreated HCC that only requires a clinical evaluation for ascites and physical performance status and measurement of serum AFP. This simple model is particularly apt for developing country circumstances and can also be used to select patients for treatment trials.

The effect of chronic liver disease on venous thromboembolism among medically managed patients in Singapore General Hospital.

BACKGROUND: Chronic liver disease (CLD) has been suggested to be associated with venous thromboembolism (VTE) in western populations. However, little is known about the risk effects of CLD on VTE among Asians. OBJECTIVE: To compute the prevalence of VTE among hospitalised Asian patients, and to evaluate the pattern and scale of risk effects of CLD on VTE occurrence. METHOD: Retrospective study of hospital discharge database from 2004 to 2011 to identify patients with VTE and CLD using International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Australian Modification (ICD-9-AM) codes. RESULTS: Of 199904 medically managed inpatients during the 8years, 1744 (0.9%) patients had VTE. Patients with CLD had significant higher prevalence of VTE (non-cirrhosis CLD 1.5%, cirrhosis 2.0%) than patients without CLD (0.8%, p<0.001). In the logistic regression analyses, non-cirrhosis CLD (odds ratio, OR 1.4, 95% CI 1.2-1.7, p<0.001) and cirrhosis (OR 1.5, 95% CI 1.2-2.0, p=0.002) were significant predictors of VTE after adjustment for age, gender, ethnicity, hospital long stayer, cancer, infectious disease, and other comorbid conditions such as diabetic mellitus, anaemia, and cardiovascular, cerebrovascular, renal and pulmonary diseases. CONCLUSION: CLD, particular liver cirrhosis, increases the risks of VTE in hospitalised Asian patients. As CLD patients are perceived to be at risks of bleeding due to the prolonged clotting times and thrombocytopenia, the results of this study brings attention to opposite end of the haemostatic pendulum in patients with chronic liver disease.

The burden of diabetes mellitus in elderly patients from an Asian tertiary hospital.

SUMMARY: Diabetes mellitus (DM) has been declared as a global public health threat to society. However, the burden of the disease in elderly Asian patients has not been described. The aim of the study is to assess the disease burden of DM and its associated adverse outcomes in elderly patients from an Asian hospital using the hospital inpatient database. METHODS: Retrospective study of hospital discharge database from 2004 to 2008 to identify patients aged 65 years and above with DM and its associated 'adverse outcomes' using International Statistical Classification of Diseases and Related Health Problems, 9th Revision, Australian Modification (ICD-9-AM) codes. RESULTS: Of 89,875 hospitalized patients aged 65 years and above over the 5 years, 31,124 (34.6%) patients had DM, and the percentage of DM cases increased steadily from 34.3% to 35.6%. Prevalence of DM-associated adverse outcomes was higher in DM patients than in non-DM patients (53.8% vs. 31.5%, p<0.001). For trends over time, the adverse outcomes decreased in both DM patients (58.1% to 53.6%) and non-DM patients (34.3% to 31.4%, all p<0.001). All disease-specific adverse outcomes except renal disease decreased over time both in DM and non-DM patients (all p<0.05). There were increased trends over time for renal disease in both DM patients (16.1% to 23.2%, p<0.001) and non-DM patients (6.7% to 10.4%, p<0.001). CONCLUSION: The burden of DM in this group of elderly patients is high. Elderly patients with DM experienced much higher rates of the adverse outcomes.

Treatment of chronic hepatitis C in patients with end-stage renal disease and hemophilia--the Singapore experience.

OBJECTIVE: The aim of this study was to determine the response to treatment with interferon-alpha (IFN-alpha) in patients with chronic hepatitis C who had end-stage renal disease (ESRD) or hemophilia in Singapore. METHODS: Treatment-naive hepatitis patients with ESRD or hemophilia were given IFN-alpha(2a) 3 million units three times per week for 12 months in an open-label study. Hepatitis C virus RNA was determined before treatment, at the end of treatment and 6 months thereafter. Regular clinical examinations including blood counts and biochemistry were carried out during and after the treatment. RESULTS: Nine consecutive patients with ESRD (8 men and 1 woman) and 6 consecutive male patients with hemophilia, with a mean age of 43 and 40 years, received treatment. Patients in both groups were predominantly infected with hepatitis C virus genotype 1 and had significant cytopenia affecting all three cell lines during the treatment; only 1 patient developed serious neutropenia, temporarily demanding a reduction of his IFN dose. Biochemical and virological responses at the end of treatment were accomplished by 8 of the 9 (89%) patients with ESRD and 4 of the 6 (67%) patients with hemophilia; however, 1 patient with ESRD and 2 with hemophilia relapsed after the treatment. Four of the 7 patients with ESRD who had sustained virological response underwent successful kidney transplantation later on. CONCLUSION: Monotherapy with IFN-alpha for 12 months is safe for treatment of the patients with chronic hepatitis C who had ESRD or those with hemophilia. A higher sustained virological response rate was observed in patients with ESRD than in those with hemophilia (78 vs. 33%).

Clinical characteristics of ulcerative colitis in Singapore, a multiracial city-state.

BACKGROUND: Ulcerative colitis (UC) is rare in Asia. Singapore is an ethnically heterogeneous city-state with a population made up of Chinese (77%), Indians (7.5%), and Malays (14%). This study describes and compares the characteristics of Chinese, Malay, and Indian patients with UC. STUDY: Retrospective chart review was performed of 235 patients seen in the largest tertiary care hospital in Singapore between 1971 and June 2000. RESULTS: There were 169 (72%) Chinese, 24 (10%) Malays, and 42 (18%) Indians with UC. Male-to-female ratio was 1.8:1 (150:85). Most patients in all three races presented between the ages of 20 and 39 years. No bimodal peak in the age at presentation was seen. The median period from onset of symptoms to diagnosis was 1 month in all three races. More Malay (57%) and Indian (55%) patients had colitis extending proximal to splenic flexure at presentation compared with Chinese (32%) patients (p = 0.04). There were more Indian patients (29%) with severe disease at onset compared with Chinese (12%) and Malay (22%) patients (p = 0.035). Thirty-one percent of patients had only one episode of colitis, 12% were steroid dependent, and 4% were steroid refractory. Proctocolectomy was needed in 31 (18.3%) Chinese, 3 (12.5%) Malay, and 4 (9.5%) Indian patients. Extraintestinal manifestations were found in 6% of the Chinese, 12% of Malay patients, and 14% of Indian patients. The most common extraintestinal manifestation was arthritis, present in 6.4% of patients. CONCLUSION: There were more Indians with UC than expected in this population. Whereas Indian and Malay patients have more extensive and severe disease at presentation than Chinese patients, this does not predict for more refractory disease or a greater need for surgery.

Molecular characterization of hepatitis B virus surface antigen mutants in Singapore patients with hepatocellular carcinoma and hepatitis B virus carriers negative for HBsAg but positive for anti-HBs and anti-HBc.

BACKGROUND AND AIMS: Mutations on the a-determinant of hepatitis B virus surface antigen (HBsAg), capable of escaping detection and vaccination, are identified in HBsAg-positive/anti-HBs-positive vaccinated infants. We studied the prevalence of these mutants in HBsAg-negative/anti-HBc-positive chronic HBV carriers and patients with hepatocellular carcinoma (HCC). METHODS: DNA sequence coding for the antigenic a-determinant of HBsAg was amplified from either HCC genomic DNA or serum samples of the selected patients and sequenced. The replicative mutant genomes were reconstituted in vitro and their reactivity to commercial kits measured. RESULTS: Mutations within and/or outside the a-determinant were identified in patients seronegative for HBsAg. They were then reconstituted in vitro and transiently transfected into HepG2 cells. Culture medium containing secreted HBV viral particles was collected and assayed for their binding to commercial kits. Drastic decrease of reactivity to these kits was seen with most of the identified mutations, including those located outside the a-determinant. CONCLUSION: The existence of a more complex antigenic structure of HBsAg is indicated by the decreased reactivity to detection of mutations, some of which are outside the a-determinant, escape vaccination and may persist in seronegative patients. The high proportion of HBsAg mutants that are integrated in HCC genomes suggests a role of these mutants in hepatocarcinogenesis, possibly leading to mutant HBV-related HCC.