Influenza A H1N1 (2009): clinical spectrum of disease among adult patients admitted to a regional hospital in Singapore.

INTRODUCTION: The worldwide spread of Influenza A H1N1 (2009) has proceeded at an unprecedented rate, with the World Health Organization rapidly raising its influenza pandemic alert to phase six. We describe the disease spectrum of H1N1 (2009) to aid the triaging and identification of patients at risk. METHODS: This is a retrospective chart review of all confirmed H1N1 (2009) cases admitted to our institution between June and September 2009. RESULTS: The disease severity of the 153 patients studied was classified as mild (n is 75), moderate (n is 55) and severe (n is 23). 81 patients were female. The median age was 26 years. While comorbidities were more prevalent among patients with moderate-severe illness, 47.4 percent reported no pre-existing illness. Presenting complaints of breathlessness, tachycardia, low-pulse oximetry, higher leukocyte counts and C-reactive protein with low albumin levels were more commonly noted in moderate-severe illness (p-value less than 0.001). All patients received oseltamivir at a median of four days from illness onset. 18 required intensive care unit admission, with the majority (94.4 percent) within the first 24 hours of hospitalisation. The overall mortality rate was 4.6 percent. Median lengths of hospitalisation were four and nine days for moderate and severe cases, respectively. CONCLUSION: While the majority of H1N1 (2009) patients have mild illness, a subgroup can become critically ill. Prior good health is not necessarily a good discriminator against severe illness. The presence of dyspnoea, tachycardia and desaturation at triage should heighten the index of suspicion for H1N1 (2009)-related complications.

Ministry of Health clinical practice guidelines: Chronic Hepatitis B Infection.

The Ministry of Health (MOH) publishes clinical practice guidelines on Chronic Hepatitis B Infection to provide doctors and patients in Singapore with evidence-based guidance on managing important medical conditions. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Chronic Hepatitis B Infection, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website (http://www.moh.gov.sg/mohcorp/publications.aspx?id=26108). The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Patients with chronic hepatitis B infection: what is their quality of life?

INTRODUCTION: Hepatitis B (HBV) is endemic in Singapore. This study aimed to determine the quality of life of patients with chronic HBV infection (HBV carriers) on conservative management. They were reviewed in primary care facilities and in a district hospital in Singapore. METHODS: This cross-sectional survey utilised a validated Hepatitis Quality of Life questionnaire, which incorporated the SF-36 health survey, to assess a convenience sample of HBV carriers' quality of life in 14 domains. The mean scores in each domain were determined, with higher scores indicating better health. Wilcoxon-Mann-Whitney test was used in the data analysis to determine statistical significance (p-value is less than 0.05). RESULTS: The mean age of 108 participants was 44.1 (standard deviation 12.5) years. They were predominantly Chinese (90.7 percent), male (58.3 percent) and 50.7 percent of them had family members who were HBV-infected. The latter had higher scores in the hepatitis specific limitation (HLIM) domain. The majority did not have any impaired physical nor mental health. In comparison with the healthy peers in the local population, the Chinese HBV carriers scored significantly lower in the "social functioning" domain (p-value is less than 0.001), regardless of gender. CONCLUSION: The majority of HBV carriers had good physical and mental health. Physicians should recognise the impact of the chronic infection on the social aspects of daily living of the HBV carriers, and such issues should be addressed appropriately to provide better quality care.

Endosonography- vs. endoscopic retrograde cholangiopancreatography-based strategies in the evaluation of suspected common bile duct stones in patients with normal transabdominal imaging.

BACKGROUND: Endosonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are highly accurate techniques for evaluating common bile duct stones. AIM: To compare the clinical impact and costs of EUS- and ERCP-based strategies for evaluating patients with suspected common bile duct stones but normal transabdominal imaging. METHODS: The costs of EUS- vs. ERCP-based strategies were compared in patients with suspected acute biliary obstruction from common bile duct stones but normal transabdominal imaging. RESULTS: Over a 15-month period, 110 patients were recruited. EUS detected a common bile duct lesion in 73% (common bile duct stones: 68%; pancreatic cancer: 2%; ampulla tumour: 2%; cholangiocarcinoma: 1%). The sensitivity, specificity, positive predictive value and negative predictive value of EUS were 98%, 100%, 100% and 93%, respectively. EUS prevented 30% unnecessary ERCP. The mean difference in cost per patient between EUS- and ERCP-based strategies was US$166. When stratified according to clinical indications, an EUS-based strategy was costlier only in suspected biliary sepsis. Costs were similar when the indications were cholestatic jaundice, acute pancreatitis and cholestasis. CONCLUSION: EUS prior to biliary interventions in patients with suspected common bile duct stones prevented unnecessary ERCP. It allowed a definitive diagnosis to be made prior to more invasive procedures.

Endoscopic ultrasound-guided fine needle aspiration in the evaluation of suspected lung cancer.

BACKGROUND AND AIM: The role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis and staging of lung cancer is still not fully explored. This prospective study aimed to define the effectiveness of EUS-FNA as an adjunct to computer tomography (CT) and bronchoscopy in the evaluation of suspected lung cancer in routine clinical practice. METHODS: Over a period of 20 weeks, the data of 16 consecutive patients suspected of lung cancer on account of respiratory symptoms, and/or the findings of either a mass or mediastinal lymph nodes on helical CT, who were referred for evaluation by EUS, were prospectively collected. Fourteen of these patients underwent sequential bronchoscopy followed by EUS-FNA in the same setting. RESULTS: Bronchoscopy was performed in 15 patients, while EUS was performed in all 16 patients. Bronchoscopy diagnosed 9 cases of non-small-cell lung cancer (NSCLC) but was falsely negative in 3 cases of malignancies, which were all established by EUS-FNA of mediastinal lymph nodes (2 cases of NSCLC and 1 case of esophageal squamous cell cancer). EUS-FNA also diagnosed advanced NSCLC in another patient who did not undergo bronchoscopy, such that eventually 13 patients were diagnosed to have malignancies. Distant metastases were diagnosed by EUS-FNA in 4 cases of NSCLC (2 cases of left adrenal gland and 2 cases of pancreatic metastases). Two patients were diagnosed to have sarcoidosis and 1 patient was diagnosed to have pneumoconiosis eventually. CONCLUSIONS: EUS-FNA is useful as an adjunct to CT and bronchoscopy in the evaluation of suspected lung cancer.

Rabeprazole vs esomeprazole in non-erosive gastro-esophageal reflux disease: a randomized, double-blind study in urban Asia.

AIM: Gastro-esophageal reflux disease (GERD) is becoming increasingly common in Asia. Data on the efficacy of proton pump inhibitors in patients with non-erosive GERD (NERD) in Asia is lacking. This double-blind study compared the efficacy and safety of rabeprazole with esomeprazole in relief of symptoms in patients with NERD. METHODS: One hundred and thirty-four patients with reflux symptoms of NERD and normal endoscopy were randomized to receive rabeprazole 10 mg or esomeprazole 20 mg once daily for 4 wk. Symptoms were recorded in a diary and changes in severity of symptoms noted. RESULTS: At 4 wk of treatment, rabeprazole 10 mg and esomeprazole 20 mg were comparable with regards to the primary endpoint of time to achieve 24-h symptom-free interval for heartburn 8.5 d vs 9 d and regurgitation 6 d vs 7.5 d. Rabeprazole and esomeprazole were also similarly efficacious in term of patient's global evaluation with 96% of patients on rabeprazole and 87.9% of patients on esomeprazole, reporting that symptoms improved (P = NS). Satisfactory relief of day- and night-time symptoms was achieved in 98% of patients receiving rabeprazole and 81.4% of patients receiving esomeprazole. Adverse events were comparable in both groups (P = NS). CONCLUSION: Rabeprazole 10 mg has a similar efficacy and safety profile in Asians with NERD as esomeprazole 20 mg. Further study is necessary to investigate whether the small differences between the two drugs seen in this study are related to the improved pharmacodynamic properties of rabeprazole. Both drugs were well tolerated.

A qualitative study of health-seeking behavior of Hepatitis B carriers.

INTRODUCTION: Asymptomatic Hepatitis virus (HBV) carriers are often followed up at primary and secondary care centres in Singapore. Compliance to disease monitoring is perceived to be a barrier in their management. The study used qualitative methods to determine the health-seeking behavior of HBV carriers. Understanding such behavior will enable the attending physicians to optimise their care and promote regular disease surveillance. METHODS: Data were collected from 39 HBV carriers from primary and secondary healthcare centres, with different demographic profiles in eight respective focus group discussions (FGD). A nurse conducted the FGDs using a semi-structured guideline. The qualitative data were analysed using standard content analysis technique. RESULTS: There was evidence of doctor hopping among the HBV carriers in seeking the follow-up of their disease. Cost of review and investigations and preference for specialists' care appeared to be determinants of the sites of disease monitoring. Compliance to follow-up seemed to be sub-optimal, arising from apathy, denial, perceived inconvenience and cost of review. A significant proportion of the carriers had tried alternate therapy, took liver supplements but most found them to be ineffective. Most carriers had adopted healthier lifestyle after their diagnosis with regular exercise, smoking cessation and alcohol abstinence. CONCLUSION: Many HBV carriers' inadequate understanding of the disease resulted in indifferent or inappropriate health-seeking behavior towards their disease management. There is room for health education for these carriers to enhance their awareness of the disease and improve compliance to disease monitoring.

Post-SARS psychological morbidity and stigma among general practitioners and traditional Chinese medicine practitioners in Singapore.

INTRODUCTION: The severe acute respiratory syndrome (SARS) outbreak has been unique in recent history in its rapidity of transmission, its concentration in healthcare settings, and the large number of healthcare workers who have been infected. This study aims to examine the psychological impact of SARS on general practitioners (GPs) and traditional Chinese medicine (TCM) practitioners in Singapore. MATERIALS AND METHODS: Two months after the SARS outbreak, all the GPs and TCM practitioners in Singapore were mailed a set of self-reported questionnaires, which included the General Health Questionnaire (GHQ), the Impact of Event Scale-R (IES-R), and a questionnaire to measure the perception of stigma. RESULTS: A total of 721 (29%) GPs and 329 (22%) TCM practitioners responded to the survey. Significantly more GPs had worked in SARS affected facilities and had been directly involved in the care of patients with SARS than the TCM practitioners (P <0.001). Those GPs who were directly involved in the care of patients with SARS were significantly more likely to be GHQ case as compared to those not involved in the care of patients with SARS (P = 0.02; OR = 2.9; 95% CI, 1.3-6.3). The mean score of the GHQ somatic, anxiety and social dysfunction subscales were significantly higher in GPs as compared to TCM Practitioners (P <0.001). The GHQ total score as well as the subscales was significantly correlated with the IES-R and stigma subscales (P <0.05). CONCLUSION: The fear, uncertainty and stigma caused by SARS are associated with psychological distress among some of the primary healthcare providers in Singapore.

Review of peripherally inserted central catheters in the Singapore acute-care hospital.

Peripherally inserted central catheters are frequently used whenever reliable central venous access is required for a prolonged period of time. The objective of this study was to review utilisation profile, complication rates and outcomes of patients who were treated in our hospital with the therapy that required placement of the peripherally inserted central catheter. We reviewed the medical records of all patients who had peripherally inserted central catheter placed between the beginning of July and the end of October 2002. Five patients who remained hospitalised at the time of review (six weeks after the last day of study period) were excluded. Seventy-eight patients with 94 peripherally inserted central catheters were analysed in detail. Sixty-four peripherally inserted central catheters (68.1%) were placed for prolonged antibiotic therapy, 27 (28.7%) mainly to administer total parenteral nutrition and 3 (3.2%) were inserted for other reasons. Catheters were in place before removal for a mean 17.2 days. Forty-eight catheters (51.1%) were removed after completion of therapy on average 20.2 days after insertion. Complications were frequent but minor. Thirty-three catheters (35.1%) were removed due to catheter-related complications. The most common complication were phlebitis followed by accidental removal. In summary, peripherally inserted central catheters proved to be reasonably safe and a reliable way of providing therapy requiring prolonged intravenous access. Complications were frequent but relatively minor. Complication rates in our study were similar to those reported in other studies on this subject. Peripherally inserted central catheters remain a convenient and reasonable alternative to other centrally or peripherally inserted venous devices.

Validation of 13C-urea breathtest for the diagnosis of Helicobacter pylori infection in the Singapore population.

INTRODUCTION: Several tests are available for determining the presence of Helicobacter pylori (H. pylori) infection. These may be invasive or non-invasive. The carbon urea breath test (C-UBT) is generally considered to be a simple, non-invasive and accurate test for the detection of H. pylori infection both before and after treatment. Commercially available 13C-UBT kits are generally validated in their country of manufacture and the stated accuracy of their tests may not be applicable to our local population. AIM: The aim of our study was to determine the accuracy of a commercial 13C-urea breath test kit, Hp-Plus (Utandningstester i Sverige AB, Sweden), in the Singapore population. PATIENTS AND METHODS: One hundred patients for oesophago-gastro-duodenoscopy (OGD) were recruited into this prospective study. Gastric biopsies were obtained for the biopsy urease test and histological examination. Blood samples were obtained for H. pylori serology. Breath samples were then obtained at baseline and after consumption of 100 mg of labelled 13C-urea. The presence of H. pylori infection was defined by a positive result on any two of the three tests (biopsy urease test, histology, serology) performed for the detection of H. pylori. Using this "gold standard", the sensitivity, specificity, and positive and negative predictive values of the 13C-UBT were calculated. RESULTS: In the Singapore population, the 13C-UBT (Hp plus) has a sensitivity and specificity of 94.2% and 100% respectively for the detection of H. pylori infection. The positive predictive value and negative predictive value of the 13C-UBT is 100% and 88.6% respectively. CONCLUSION: The 13C-UBT is a simple, safe, and accurate non-invasive test for the detection of H. pylori infection, making it a valuable tool in local clinical practice.

Liver transplantation in patients with hepatitis B virus infection: outcome in Asian versus white patients.

Previous studies have found that Asian patients transplanted for hepatitis B virus (HBV) infection had worse outcomes than white patients. The aim of this study was to compare outcomes in Asian and white patients listed for liver transplantation for HBV infection. Data of all patients with HBV infection listed for liver transplantation between January 1996 and June 1998 from 20 centers in North America were collected using a survey. Total patients enrolled were 325 (171 whites, 126 Asians, 28 other races). There was no difference in demographics, liver biochemistry, and HBV replicative status between Asians and whites at the time of listing. More Asians had hepatocellular carcinoma and fewer Asians had hepatitis C or D virus coinfection. At the time of this survey, 70 Asians (55%) and 99 whites (58%) had been transplanted. Actuarial 2-year survival posttransplantation for Asians (88%) and whites (92%) was similar. Recurrent HBV infection occurred in 8 (11%) Asians and 12 (12%) whites. Five patients with recurrent HBV infection died, 4 of whom were Asian. Actuarial 2-year survival for Asians versus whites with recurrent HBV infection was 60% versus 90% (P =.04). In this large cohort of patients, overall survival and recurrent HBV infection posttransplantation were comparable between Asians and whites. However, Asians with recurrent HBV infection posttransplantation had significantly higher mortality.

Hepatitis B infection in patients with acute liver failure in the United States.

Occult hepatitis B virus (HBV) infection has been reported in 30% to 50% of patients with acute liver failure (ALF) in small case series. The aim of this study was to determine the prevalence of occult HBV infection in a large series of ALF patients in the United States and the prevalence of precore and core promoter variants in patients with ALF caused by hepatitis B. Sera from patients in the US ALF study and liver, when available, were tested using nested polymerase chain reaction (PCR) with primers in the HBV S and precore regions. PCR-positive samples were sequenced. Sera and/or liver from 139 patients (39 males, 100 females; mean age, 42 years) enrolled between January 1998 and December 1999 were studied. Twelve patients were diagnosed with hepatitis B, 1 with hepatitis B+C+D coinfection, and 22 had indeterminate etiology. HBV DNA was detected in the sera of 9 (6%) patients; all 9 had ALF caused by hepatitis B. HBV genotypes A, B, C, and D were present in 4, 3, 1, and 1 patients, respectively. Seven of these 9 patients had precore and/or core promoter variants. Liver from 19 patients were examined. HBV DNA was detected in the liver of 3 patients with ALF caused by hepatitis B, but in none of the remaining 16 patients with non-B ALF. Contrary to earlier reports, occult HBV infection was not present in this large series of ALF patients in the United States. HBV precore and/or core promoter variants were common among US patients with ALF caused by hepatitis B.

Hepatocellular carcinoma: an Asian perspective.

Hepatocellular carcinoma (HCC) is one of the most frequently occurring malignancies in Asia. The incidence exceeds 30 cases/100,000/year in the east Asian region. Worldwide, it accounts for almost 1 million deaths/year. The high incidence in Asia is due to the high prevalence of chronic viral hepatitis, mainly chronic hepatitis B. With the introduction of universal vaccination for hepatitis B in some Asian countries in the mid 1980s, some of these countries are experiencing a decline in the incidence of HCC. This probably underscores the point that HCC caused by hepatitis B is a malignancy preventable by vaccine. Due to the relative paucity of symptoms in the early stages and the rapid doubling time of the tumor, most HCCs are discovered late in advanced stages at presentation. Most Asian countries have adopted a screening program for patients at risk. Earlier and smaller HCCs are detected through such programs but these programs have yet to demonstrate improved patient survival. Physicians managing patients with HCC are faced with two main challenges, the malignancy itself and the underlying liver disease. The extent of the tumor and the existing liver function limits the therapeutic choices available. Hepatic resection remains the treatment of choice. However, the majority of patients present with nonresectable tumors. Transarterial chemoembolization, percutaneous ethanol injection and radiofrequency ablation are the other treatment modalities. In patients with small tumors (<5 cm) and poor liver function, liver transplant offers a viable treatment alternative. In summary, the risk factor for HCC in Asia is predominantly chronic hepatitis B. Universal vaccination against hepatitis B is likely to reduce the incidence. The prognosis and outcome of treatment remains poor with a 5-year survival of 35% for patients treated surgically and less than 10% for nonresectable tumors. Current management is aimed at earlier detection and more effective treatment of early HCC. In future, the challenge will be managing HCC in the premalignant stage.

Autoimmune hepatitis in Singapore: a rare syndrome affecting middle-aged women.

BACKGROUND AND AIM: The prevalence of autoimmune hepatitis in Singapore is unknown. Over a period of 7 years, 24 cases were diagnosed in a district general hospital in Singapore (Toa Payoh Hospital) by using the scoring system proposed by the International Autoimmune Hepatitis Group in 1993. The aims of our study were to determine the prevalence of autoimmune hepatitis in Singapore, and to investigate the characteristics and prognosis in the mainly Chinese population. METHODS: The case records of all 24 patients were reviewed, and the following parameters were recorded: age at presentation, sex, symptoms and signs at presentation, past exposure to hepatotoxic drugs, alcohol intake, blood transfusion laboratory and histological tests used to determine autoimmune hepatitis, response to treatment, complications, and survival. RESULTS: The mean age of patients was 57 years old. There was a female-male ratio of 11:1. Forty-two percent of the patients were cirrhotic at presentation. The prevalence of autoimmune hepatitis was four per 100 000, with no significant difference between Chinese, Malay and Indian patients (Odds ratio of 0.38 by the chi-squared test). Eighty-nine percent of the patients responded to treatment with the induction of prednisolone, but the relapse rate was 61%. Treatment failure occurred in one patient. The mortality rate during the 7 years of follow up was 21%, and all were caused by complications of cirrhosis. The survival at 5 years was 71%, with a standard error of 0.13. CONCLUSION: Autoimmune hepatitis in Singapore is mainly a disease in older women. The response to steroid treatment is good, with a 5-year survival rate of 71%.

Racial differences in the prevalence of ulcerative colitis and Crohn's disease in Singapore.

BACKGROUND: The aim of this study was to determine the prevalence rates of inflammatory bowel disease in the different races in Singapore. METHODS: The patients studied consisted of 58 people with an established diagnosis of ulcerative colitis (UC) and Crohn's disease (CD) as determined by a combination of clinical, radiological, endoscopic and histological criteria. The patients were residents of a well-defined geographical area in the northern part of Singapore and had been referred to the single regional hospital. Epidemiological data including sex, age, ethnicity, family history and disease type and extent were collected from case records and patient interviews. RESULTS: There were 37 UC and 21 CD patients. Of the patients with UC, 67.5% were Chinese, 13.5% were Malay and 19% were Indian. The CD group consisted of 81% Chinese, 9.5% Malay and 9.5% Indian patients. The study population from which the patients were drawn was approximately 0.5 million in size. CONCLUSIONS: The overall prevalence of UC was 6 per 100,000 and of CD was 3.6 per 100,000 in Singapore. There were disproportionately more Indians suffering from UC, with a prevalence of 16.2 per 100,000 in comparison with six per 100,000 for Chinese and seven per 100 000 for Malays. The relative risk of UC in Indians is 2.9-fold greater than for the Chinese (CI= 1.25-6.7) which was statistically significant. This trend was not seen for CD.

Metronidazole-resistant Helicobacter pylori in an urban Asian population.

BACKGROUND: Helicobacter pylori eradication is the mainstay in the treatment of H. pylori-associated peptic ulcer disease. Metronidazole is an important component in most eradication regimens. However, the presence of metronidazole-resistant H. pylori adversely affects the efficacy of such regimens. We aimed to study the prevalence of metronidazole resistance in our population, and the factors associated with its presence. METHODS AND RESULTS: From September 1993 to September 1996, 459 H. pylori isolates were collected and analysed. The overall resistance rate was 62.7%. The rate was significantly higher among women compared with men (P < 0.05). When the results were analysed according to each year, there was a significant increase in the resistance rate from 50.5% in the first year to 72.7% in the third year (P = 0.0039). CONCLUSIONS: There was a significant rise in the prevalence of metronidazole resistance over a 3-year period. The presence of metronidazole resistance adversely affects the eradication rates of nitroimidazole-based regimens. Hence, in a population with a high prevalence of metronidazole resistance, the use of non-nitroimidazole-based therapy may be more efficacious. This information on resistance rates is important for the empirical choice of antibiotic against H. pylori in a population.

Non-steroidal anti-inflammatory drugs, Helicobacter pylori and bleeding gastric ulcer.

BACKGROUND: Helicobacter pylori infection and NSAID usage are considered to be independent risk factors for gastric ulcer (GU). Whether they interact to influence the risk of bleeding in GU is unclear. AIM: To determine the prevalence of H. pylori infection and NSAID ingestion in a group of patients with GU and determine their roles in bleeding and non-bleeding GU. METHODS AND RESULTS: From January 1993 to June 1996, a total of 217 GU patients (150 male, 67 female, median age 61 years, range 26-94) were eligible for the study. Eighty-five per cent were H. pylori-positive and 15% were H. pylori-negative. NSAID usage within 4 weeks prior to endoscopy was present in 30%, more in the H. pylori-negative than H. pylori-positive patients (59% vs. 25% P = 0.0002). Aspirin was most commonly used (43%). One hundred patients bled from GU (69 male, 31 female, mean age 67 years, range 26-94) and 117 did not (81 male, 36 female, mean age 57 years, range 28-86). Univariate logistic regression showed that advanced age (>/= 65 years) and NSAID usage carried an increased risk of bleeding GU (odds ratio 3.4 and 6.8, respectively) while H. pylori infection alone was not associated with additional risk (OR = 0.8). However, when three variables were considered jointly in a multiple logistic regression, the OR associated with H. pylori infection increased to 2.4, suggesting that in the presence of NSAIDs and advanced age, H. pylori also increases the risk of bleeding GU, indicating an interaction between the variables. CONCLUSION: NSAID usage and advanced age are risk factors for bleeding GU, whereas H. pylori infection by itself is not. In the presence of NSAIDs and advanced age, an increased risk of bleeding GU with H. pylori is observed, indicating the possibility of an interaction between these factors.