Original Article

Chia YC, Yeoh ESH, Ng CJ, Khoo EM, Chua CT
Correspondence: Prof Chia Yook Chin, chiayc@um.edu.my

ABSTRACT
Introduction Calcium channel blockers are well established modalities for the treatment of hypertension. However, in spite of the availability of many efficacious agents, hypertension control continues to be poor. One reason is poor tolerability due to adverse events. Racial differences also exist. Lercanidipine, a third-generation calcium channel blocker, is associated with better tolerability. However, it has not been studied in the Asian population. This study examines its efficacy and tolerability in Asian subjects of different ethnicities.
Methods This was an eight-week open label study of adults with mild to moderate hypertension. Blood pressure (BP), pulse rate, self-administered symptom check and laboratory evaluations were done at baseline. Patients were prescribed 10 mg lercanidipine, with up-titration to 20 mg if BP was not controlled at Week 4. Baseline evaluations were repeated at Week 8. Adverse events were also enumerated.
Results 27 patients (mean age 53.4 +/- 12.1 years) completed the study. The baseline systolic BP (SBP), diastolic BP (DBP) and heart rate was 159 +/- 12.2, 96.6 +/- 7.7 mmHg and 71 +/- 13/min, respectively. Three racial groups were represented. SBP and DBP decreased significantly after four weeks of therapy. A further reduction to 139 +/- 14.3 and 88 +/- 9.8 (p-value is less than 0.0001) was seen in Week 8. The absolute SBP and DBP reduction was 20.5 mmHg (95 percent confidence interval [CI] 16.5–24.5, p-value is less than 0.0001) and 9.3 mmHg (95 percent CI 6.2–12.5, p-value is less than 0.0001), respectively. All adverse symptoms, except for palpitations, were reduced at the end of the study.
Conclusion Lercanidipine is efficacious and well tolerated in Asians of different ethnicities. Its BP lowering effects and tolerability in Asians appear to be similar to other studies on Caucasians and other calcium channel blockers.

Keywords: blood pressure, calcium channel blockers, hypertension, lercanidipine
Singapore Med J 2009; 50(5): 500-505

Yousuf RM, Fauzi ARM, How SH, Akter SFU, Shah A
Correspondence: Dr R M Yousuf, drmyrathor@yahoo.com

ABSTRACT
Introduction Optimal patient care varies considerably from place to place and is influenced by scientific as well as social developments. The purpose of this study was to investigate awareness and pertinent issues regarding informed consent among hospitalised patients and to determine lapses, in order to improve the standard of care.
Methods A questionnaire-based cross-sectional survey was conducted among inpatients at a tertiary care level hospital.
Results 90 percent of patients were aware of their rights, and 85 percent had enough information regarding their illness and modality of treatment. However, treatment options were discussed with 45 percent of cases only, and 65 percent of patients were informed of their duration of treatment. Most of the patients from the surgical group, haemodialysis unit and those with minor ailments were very satisfied with the doctors (92 percent, 86 percent and 96 percent, respectively), as opposed to only 36 percent of cancer patients and 70 percent of acquired immunodeficiency syndrome (AIDS) patients (p-value is less than 0.0001). Almost all patients (99 percent) said that their religious beliefs were respected by the staff and they had no problems in accessing them in times of need. Informed consent was obtained by the doctor in 98 percent of cases and by the nurse in two percent. 98 percent of the patients mentioned that their treatments/examinations were conducted in an atmosphere of privacy and that their personal information was kept confidential by their doctors.
Conclusion Patients were reasonably informed about their illness. Their privacy and religious beliefs were duly respected. Treatment options and the duration of treatment were not discussed with all patients. Cancer and AIDS patients were less satisfied with the attending staff. The results suggest that there is a need for periodic surveys of patient satisfaction with the quality of care.

Keywords: informed consent, patient-centred care, patient confidentiality, patients’ privacy, patients’ rights
Singapore Med J 2009; 50(5): 494-499

Ngow HA, Wan Khairina WMN, Teh LK, Lee WL, Harun R, Ismail R, Salleh MZ
Correspondence: Dr Harris Ngow, harrisngow@gmail.com

ABSTRACT
Introduction Genetic polymorphisms of CYP2C9 among different populations in different geographical regions could be different. CYP2C9 has been reported to be the enzyme responsible for the metabolism of many drugs, including warfarin and other drugs with a narrow therapeutic index. Realising the importance of inter-individual differences in the genetic profile in determining the outcome of a drug therapy, this study was conducted to explore the types and frequencies of CYP2C9 alleles in healthy and warfarin-treated Malays and Chinese, the two major ethnic groups in Malaysia. We aimed to evaluate the prevalence of the types and frequencies of common CYP2C9 alleles (*1, *2, *3 and *4) among the healthy unrelated individuals and diseased patients prescribed with warfarin.
Methods A total of 565 Malay and Chinese subjects, including 191 patients prescribed warfarin, were recruited into the study. The healthy unrelated volunteers were also blood donors and they were confirmed to be physically fit before participating in the study. For the patients group, their medical records were reviewed for the relevant clinical data. 5 ml of blood was taken from each subject, and DNA was isolated and used for identification of the CYP2C9 allele *1, *2, *3 and *4 using nested-allele-specific-multiplex-polymerase chain reaction.
Results CYP2C9*1, *2 and *3 were detected among the healthy unrelated individuals but only CYP2C9 *1 and *3 were found in the diseased patients. Among the healthy Malays, 92.8 percent had CYP2C9*1/*1, 2.6 percent had CYP2C9*1/*2 and 4.6 percent had CYP2C9*1/*3 genotypes. Among the Chinese, 92.3 percent had CYP2C9*1/*1 and 7.7 percent had CYP2C9*1/*3, but CYP2C9*2 and *4 were not found in the Chinese. Among the warfarin-treated group, only CYP2C9*1 and *3 were detected. Even though some alleles were not detected among the patients, suggesting the possible role of CYP2C9 in certain disorders, the sample size of the current study is too small to be able to arrive at any conclusive results.
Conclusion Based on the above-observed genotypes, the prevalence of CYP2C9*2 and *3 was low in healthy and warfarin-treated Malays and Chinese in Malaysia. Further studies are required to support the clinical effectiveness of pharmacogenomics testing.

Keywords: CYP2C9 frequency, genetic polymorphism, pharmacogenomics testing, warfarin
Singapore Med J 2009; 50(5): 490-493

Siddiqi A, Khan DA, Khan FA, Razzaq A
Correspondence: Dr Dilshad Ahmed Khan, saadbinqamar@hotmail.com

ABSTRACT
Introduction Amikacin is a commonly-prescribed drug used for the empirical treatment of bacterial infections in neonates. A marked change in the pharmacokinetics of amikacin has been reported during neonatal life. Amikacin has a very narrow therapeutic range and can cause very serious side effects such as nephrotoxicity and ototoxicity. The current therapeutic dose of amikacin, i.e. 15 mg/kg of body weight, may increase the risk of toxicity in preterm infants with immature renal functions. We aimed to determine the frequency of amikacin toxicity in preterm as compared to term infants by measuring its serum trough levels following the administration of the current therapeutic dose.
Methods A comparative study was conducted at the neonatal intensive care unit of the Military Hospital, Rawalpindi, Pakistan. A total of 104 infants (52 term and 52 preterm) receiving amikacin at a dose of 15 mg/kg of their body weight, once daily for bacterial infection, were included. After clinical evaluation, serum creatinine levels were measured at admission and on the third day. Amikacin trough levels were taken after 72 hours of therapy and measured on the TDx Abbot Drug Analyser.
Results The gestational age range was 37–40 weeks in term and 29–36 weeks in preterm infants. The term and preterm infants had a median weight of 2.8 kg and 2.1 kg, respectively. The preterm infants had significantly higher median (range) 11.33 (1.50–42.60) ug/ml levels of serum amikacin as compared to 8.5 (2.8–33.0) ug/ml in term infants (p-value is less than 0.01). The preterm infants had a high frequency of toxic 32 (62 percent) and subtherapeutic 12 (23 percent) levels, as compared to 11 (21 percent) and 5 (10 percent) in term infants, respectively. Serum amikacin levels revealed a positive correlation with post-dose serum creatinine (r equals 0.48; p-value is less than 0.05).
Conclusion This study demonstrated that the current practice of amikacin treatment for bacterial infection needs to be adjusted due to unique pharmacokinetic variability in preterm infants. There is a need for regular therapeutic drug monitoring and renal function assessment in all infants receiving amikacin therapy in order to avoid nephrotoxicity.

Keywords: amikacin, bacterial infection, neonatal sepsis, nephrotoxicity, serum trough levels, therapeutic drug monitoring
Singapore Med J 2009; 50(5): 486-489

Torkaman M, Afsharpaiman S, Hoseini MJ, Moradi M, Mazraati A, Amirsalari S, Kavehmanesh Z
Correspondence: Dr Shahla Afsharpaiman, safshar@razi.tums.ac.ir

ABSTRACT
Introduction Sepsis is a common complication in the neonatal intensive care unit. It is most common in the smallest and most premature infants in whom the clinical presentation can be subtle and nonspecific. The objectives of the present study were to identify the most common organisms causing sepsis and their associations with thrombocytopenia.
Methods This is a retrospective case analysis of blood culture positive patients between March 2003 and July 2007 in a single centre. We enrolled 53 eligible neonates whose blood culture yielded positively for any organism. Blood for the culture was obtained from a peripheral vessel. The data was analysed for differences in platelet and neutrophil count in terms of the microorganisms causing sepsis using chi-square and Fisher’s exact tests, analysis of variance and Kruskal-Wallis, as appropriate.
Results The most common organism in the blood culture was Enterobacter spp. with 21 cases (39.6 percent) and the least common was coagulase-positive Staphylococcus spp. The most common organisms in infants with normal weight and early onset sepsis were coagulase-positive Staphylococcus spp. (50 percent and 36.7 percent, respectively), while in other neonates with low birth weight, very low birth weight and late onset sepsis, the most common organism was Enterobacter spp. (40.9 percent, 71.4 percent and 47.8 percent, respectively). The patients with Enterobacter spp. sepsis had a higher incidence of thrombocytopenia. The mortality rate was 15.1 percent (8/53 cases), which was significantly higher among those with the Enterobacter spp. sepsis (five cases, p-value is 0.033).
Conclusion Our study shows the changes in the pattern of late onset neonatal infections in the neonatal intensive care unit. Enterobacter spp. is the most common organism causing neonatal sepsis accompanying thrombocytopenia.

Keywords: Enterobacter spp., neonatal infection, neonatal sepsis, thrombocytopenia
Singapore Med J 2009; 50(5): 482-485

Low SY, Eng P
Correspondence: Dr Su-Ying Low, low.su.ying@sgh.com.sg

ABSTRACT
Introduction Infection with human immunodeficiency virus (HIV) is the most well-known risk factor for the development of tuberculosis (TB). The joint statement by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America recommends that all patients with TB undergo testing for HIV infection after counselling. We looked at physician compliance with this recommendation in Singapore.
Methods A retrospective review of the case records of all patients diagnosed with microbiologically-proven TB between September 2005 and December 2006 (inclusive) at the Singapore General Hospital was conducted.
Results Between September 2005 and December 2006, 493 patients were diagnosed with tuberculosis at our institution. HIV testing was performed in 184 patients (37.3 percent), of whom 15 (8.2 percent) was seropositive. Univariate analysis showed that an age equal to or younger than 60 years, male gender, non-pulmonary tuberculosis, inpatient location at diagnosis, and having an infectious diseases physician as the attending doctor were all significantly associated with HIV testing (p-value is less than 0.05).
Conclusion Compliance with HIV testing in all newly-diagnosed tuberculosis patients is poor, with less than 40 percent of patients being tested at our institution. We need to address the factors associated with failure to test, and reinforce to our physicians the importance of HIV testing in these patients.

Keywords: acquired immunodeficiency syndrome, human immunodeficiency virus, pulmonary tuberculosis, tuberculosis
Singapore Med J 2009; 50(5): 479-481

Phua HP, Chua AVL, Ma S, Heng D, Chew SK
Correspondence: Dr Stefan Ma, stefan_ma@moh.gov.sg

ABSTRACT
Introduction The Singapore Burden of Disease (SBoD) Study 2004 provides a comprehensive and detailed assessment of the size and distribution of health problems in Singapore. It is the first local study to use disability-adjusted life years (DALYs) to quantify the total disease burden.
Methods The SBoD study applied the methods developed for the original Global Burden of Disease study to data specific to Singapore to compute the DALYs. DALY is a summary measure of population health that combines time lost due to premature mortality (years of life lost [YLL]) with time spent in ill-health (broadly-termed disability) arising from incident cases of disease or injury (years of life lost due to disability [YLD]). DALYs, stratified by gender and age group, were calculated for more than 130 specific health conditions for the Singapore resident population for the year 2004.
Results In 2004, diabetes mellitus, ischaemic heart disease and stroke were the top three leading causes of premature death and ill-health in Singapore, and together accounted for more than one-quarter (28 percent) of the total disease burden (in DALYs). Morbidity burden (YLD) was responsible for 52 percent of the total DALYs, with diabetes mellitus, anxiety and depression, and Alzheimer’s disease and other dementias being the main sources of the total YLDs. Ischaemic heart disease, stroke and lung cancer were the major contributors to the premature mortality burden (YLL).
Conclusion This study provides an objective and systematic assessment of the fatal and nonfatal health conditions in Singapore to support priority setting in public health policies and research.

Keywords: burden of disease, morbidity, population health problems, premature mortality, public health
Singapore Med J 2009; 50(5): 468-478

Ng CL, Tambyah PA, Wong CY
Correspondence: Mr Ng Chew Lip, ngchewlip@gmail.com

ABSTRACT
Introduction Medical tuition fees have been rising in many countries, including in Singapore. No formal study has been conducted to evaluate the financial situation of medical students in relation to the cost of medical education in Singapore. This study was conducted to determine the financial profile of Singaporean medical students and the financial expenses they incur over the five-year duration of their undergraduate medical course.
Methods A questionnaire study was conducted among Year one to Year five medical students in the Yong Loo Lin School of Medicine, National University of Singapore. The following quantifiable parameters were analysed: monthly household income, financial assistance, monthly allowances and expenses.
Results 64.3 percent (735) of the 1,143 undergraduates completed the survey. 21.9 percent came from families with a monthly income of less than S$3,000, with another 26.2 percent from families with monthly incomes of S$3,000–S$5,000. The total tuition fees for a five-year medical course amounted to S$87,450. The average annual expenditure of medical students amounted to S$4,470. 31.1 percent of respondents were on loans. 14.6 percent received scholarships or bursaries.
Conclusion A five-year medical course can cost more than S$100,000 and pose a significant financial burden for students. The proportion of students who came from lower-income families was lower in medical school than at the national level, while the proportion from high-income families was significantly higher than at the national level. A significant proportion of students took loans to pay for tuition, and a smaller percentage was under scholarships and bursaries. More substantial financial assistance is required, particularly for students from lower-income families.

Keywords: education costs, medical education, medical student
Singapore Med J 2009; 50(5): 462-467

Koh SLS, Hafizah N, Lee JY, Loo YL, Muthu R
Correspondence: Dr Serena Siew Lin Koh, serena.koh.sl@kkh.com.sg

ABSTRACT
Introduction This study aimed to develop a multifaceted strategy using tailored interventions to implement a fall prevention programme, and to achieve a change in fall prevention practices and a reduction in fall incidence at an acute care hospital in Singapore.
Methods A comparative study was conducted at two acute care hospitals (intervention and control) in Singapore. Pre-intervention, post-intervention and six-month follow-up knowledge assessments of 641 nursing staff, and audits of fall rates and fall prevention practices were performed to determine the effectiveness of a multifaceted strategy with targeted interventions in supporting the implementation of a fall prevention programme.
Results The mean post-knowledge test scores at six months were statistically significantly higher (t[516] is -3.3, p-value is less than 0.01) at the intervention hospital (10.3 +/- 2.3) compared to the scores at the control hospital (9.8 +/- 1.8). Increased compliance with the use of fall risk assessment tools was evident in 99.4 percent and 99.3 percent of all patient records at the control and intervention hospitals, respectively. Following the implementation strategy for a fall prevention programme, there was a non-significant reduction in fall rates from 1.44 to 1.09 per 1,000 patient days at the intervention hospital. No reduction in the fall rate was observed at the control hospital.
Conclusion A multifaceted strategy for the implementation of a fall prevention programme was effective in increasing nurses’ knowledge and the use of the fall risk assessment, but did not have a statistically significant impact on a reduction in the fall rate. The increase in nurses’ knowledge and change in nursing practice were important markers of success in terms of fall prevention at the acute hospitals.

Keywords: clinical practice guidelines, fall incidence, fall prevention programme, fall risk assessment
Singapore Med J 2009; 50(4): 425-432

Bhagwat VR, Yadav AS, Rathod IM
Correspondence: Dr VR Bhagwat, bhagwatvr@yahoo.co.in

ABSTRACT
Introduction Geographical and ethnic factors have recently been shown to have a significant role to play in cardiovascular diseases. The exact relationship between nutritional and geographical factors in cardiovascular diseases is not very clear. This study examined the relationship of hyperhomocysteinaemia with lipid profile and antioxidants in patients with ischaemic heart disease from rural areas in Maharashtra, India.
Methods Blood cholesterol (total, high- and low-density lipoproteins cholesterol), triglycerides along with thiobarbituric acid reactive substances (TBARS), superoxide dismutase, glutathione peroxidase and catalase activities were measured in acute coronary syndrome (ACS) and chronic stable angina (CSA) patients from rural areas and in normal healthy controls from the same area. Plasma total homocysteine was measured by high pressure liquid chromatography with fluorescence detection. Folic acid and vitamin B12 were measured by chemiluminescence immunoassay.
Results The relative lipid ratios were higher in the patients and had a poor correlation with antioxidants. Total homocysteine levels were significantly higher by almost three times more than the controls. TBARS levels also showed a similar pattern, whereas antioxidant enzymes showed a significantly greater fall in ACS than CSA. There was a definite inverse relationship between total homocysteine, TBARS and antioxidants in the patients. The levels of folic acid and vitamin B12 were 3–4 times higher in the patients compared to the controls. There was a poor correlation between the total homocysteine and vitamin levels in the patients.
Conclusion Blood homocysteine is a very important biomarker of cardiovascular diseases and must be evaluated along with other risk factors. There is a higher prevalence of hyperhomocysteinaemia in rural Indian patients. There appears to be a strong association of genetic factors in the development of ischaemic heart disease in Indian patients.

Keywords: antioxidants, folic acid, homocysteine, ischaemic heart disease, lipids, vitamin B₁₂
Singapore Med J 2009; 50(4): 418-424