Vitamin B12 deficiency--a major cause of megaloblastic anaemia in patients attending a tertiary care hospital

BACKGROUND: Folate and vitamin B12 deficiencies have been known to cause megaloblastic anaemia. Since the deficiencies of these two vitamins are very common in Pakistani population, it would be imperative to investigate their role in causing megaloblastic anaemia. The objective of this study was to find out the contribution of folate and vitamin B12 deficiencies in causing megaloblastic anaemia in our patient population. METHODS: In this retrospective cohort study, clinical records of 220 patients (101 females and 119 males with an age range of 1-80 years) who presented themselves with macrocytic anaemia at the Aga Khan University Hospital were collected. Data pertaining to complete blood count and serum levels of folate and vitamin B12 were analysed. RESULTS: The mean haemoglobin (Hb) level was 6.8 +/- 0.2 gm/dl. Sixty-nine percent of the patients had severe anaemia (Hb \u3c 8 gm/dl). Mean +/- SEM values of haemoglobin, serum folate and serum B12 were not significantly different between males and females (Hb 6.4 +/- 0.3 gm/dl vs 6.3 +/- 0.3 gm/dl; folate 6.9 +/- 0.8 etag/ml vs 7.8 +/- 1 etag/ml; B12 259 +/- 65 rhog/ml vs 225 +/- 45 rhog/ml, respectively). Linear regression analysis showed that serum folate was inversely related with the mean corpuscular volume (MCV, p = 0.04). Spearman\u27s correlation analysis indicated an inverse mild association between MCV and serum folate (correlation coefficient = -0.18). Folate deficiency was 43.4%, while vitamin B12 deficiency was 78.5% in these patients. Seventy-one percent of folate-deficient patients had vitamin B12 deficiency as well, while 26.1% of patients with B12 deficiency had a co-occurrence of folate deficiency. CONCLUSION: Vitamin B12 deficiency appears to be the major factor leading to megaloblastic anaemia in our study population. Inadequate dietary intake, over-cooking of our food and poor absorption might be contributing to high prevalence of vitamin B12 deficiency in this population

High prevalence of vitamin D deficiency and insufficiency in a low income peri-urban community in Karachi

Objective: To determine the frequency of vitamin D deficiency and insufficiency in a low-income peri-urban population.Methods: The cross-sectional study was conducted in a low-income, unplanned settlement in Karachi, and comprised apparently healthy adults who were recruited randomly with informed consent. Serum levels of 25-hydroxy vitamin D were measured using a kit obtained from Roche Diagnostics. One-way analysis of variance and logistic regression were used for statistical analysis.Results: Of the 858 subjects, 507(59%) were females and 351(41%) males (age range: 18-60 years). Prevalence estimates of vitamin D deficiency (\u3c20ng/ml) and insufficiency (20.0-29.9ng/ml) were found to be 501(58.4%) and 269(31.4%), respectively. Odds ratio of vitamin D deficiency was significantly higher in females compared to males after adjusting for education and smoking status (p=0.001).CONCLUSIONS: High prevalence of vitamin D deficiency among females in one of the peri-urban areas points towards a public health problem which requires attention of the medical community

Admission creatine kinase as a prognostic marker in acute myocardial infarction

OBJECTIVES: To investigate the prognostic significance of creatine kinase (CK) in Pakistani patients suffering from acute myocardial infarction (AMI) and to find out if CK combined with troponin T (TnT) could be a better predictor for long-term adverse cardiac event. METHODS: One hundred and eighty six consecutive patients with AMI who were eligible for streptokinase (SK) treatment were included in this prospective cohort study. The relationship between their serum/plasma CK and TnT levels at the time of admission and clinical outcome was investigated over a mean follow up of 24.12 +/- 3.75 months. RESULTS: Admission CK was found to be associated with subsequent cardiac event and mortality (P \u3c 0.01 and P \u3c 0.04 respectively). Admission CK was also mildly associated with time interval between onset of symptoms to SK treatment (correlation coefficient \u27r\u27 = 0.23). Odds of encountering a cardiac event in AMI patients with above-normal CK levels (adjusted for gender) were 3.46 times higher than the odds in patients with normal CK levels. Similarly, odds of mortality in patients with positive TnT were 4.6 times the odds in patients with negative TnT. The two biochemical markers, CK and TnT, together did not provide any further information about prognosis of the disease. CONCLUSION: Admission CK is a better prognostic marker for a subsequent cardiac event, while TnT is a better predictor of mortality over a mean follow up of nearly 2 years. Together, they do not improve predictability of an adverse cardiac event

Relationship of sociodemographic factors with serum levels of vitamin D in a healthy population of Pakistan

High prevalence of vitamin D deficiency has been reported from Pakistan. Association of sociodemographic factors with vitamin D status has received little attention in this region. Therefore, we embarked on investigating the relationship of sociodemographic factors with vitamin D levels in a healthy Pakistani population. Venous blood from 226 healthy participants (age range 19-69 years) was collected and analyzed for serum concentrations of 25(OH) vitamin D [25(OH)D] and other related biomarkers. Demographic characteristics of the study participants were collected. Vitamin D deficiency (25(OH)D levels less than 20 ng/ml) was found to be 75% in this cohort. Gender, sunlight exposure and monthly household income emerged as predictors of hypovitaminosis D. Mean serum 25(OH)D levels in the groups with monthly household income less than Pakistani Rupees (PKR) 20,000, between PKR 20,000-50,000 and above PKR 50,000 were found to be 11.0±7.5, 13.9±9.6 and16.9±11.7 ng/ml, respectively. Using logistic regression the odds of having vitamin D deficiency was 3.22 (95% CI, 1.65-6.28) in the group with household income less than PKR 50,000 per month compared to the group with household income more than PKR 50,000 per month when the model was adjusted for gender and exposure to sunlight. There is an association between household income and hypovitaminosis D in a healthy Pakistani population

Polymorphisms in MTHFR, MS and CBS genes and premature acute myocardial infarction in a Pakistani population

High prevalence of premature coronary heart disease in Pakistanis compared to other populations points towards the genetic predisposition of this population to develop this disease. Since no investigations have been carried out in Pakistan to study the relationship of polymorphisms in genes involved in homocysteine cycle, the objective of the present study was to find out if there is any association of methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C; methionine synthase (MS) A2756G; cystathionine-beta-synthase (CBS) 844ins68, G919A polymorphisms with premature acute myocardial infarction (AMI) in a population of Pakistani patients with this disease. In a cross-sectional study, DNA samples of 143 AMI patients (age \u3c 45 years) and 153 healthy controls were genotyped for the above mentioned polymorphisms using PCR-RFLP methods. Plasma/serum samples of both patients and healthy controls were screened for homocysteine, folate and vitamin B12. One way ANOVA and chi-squared test were used for analysis of data. Mean plasma homocysteine levels in premature AMI patients and healthy controls were found to be 23±17.2 and 23±13.4 mumol/l, respectively which are higher than the upper normal limit of this biomarker (15mumol/l). MTHFR 677 CT genotype in healthy controls and MTHFR 677 TT genotype in AMI patients were found to have significantly increased levels of plasma homocysteine (p value \u3c 0.05), while all other polymorphisms did not show any significant difference in mean levels of homocysteine between AMI patients and healthy controls. Moreover, no association was observed between MTHFR C677T, A1298C; MS A2756C; CBS844ins68 polymorphisms and premature AMI in this population. This indicates that common polymorphisms in MTHFR, MS and CBS genes have no role in premature AMI in Pakistani population

Folic acid and vitamin B6 deficiencies related hyperhomocysteinemia in apparently healthy Pakistani adults; is mass micronutrient supplementation indicated in this population

OBJECTIVE: To determine the plasma/serum levels of homocysteine, and vitamins folate, B6 and B12, in Pakistani healthy adults.STUDY DESIGN: Cross-sectional study.PLACE AND DURATION OF STUDY: The Aga Khan University, from October 2006 to April 2008.METHODOLOGY: Fasting levels of plasma/serum folic acid, pyridoxal phosphate (PLP), vitamin B12 and homocysteine were determined in 290 apparently healthy hospital personnel from institutions in two cities of Pakistan. Spearman correlation test and linear regression analysis was conducted.RESULTS: There were 219 males and 71 females with mean age of 46+/-10.5 years and mean body mass index of 23.5 +/-3.8. Mean plasma homocysteine levels in Pakistani normal adults were found to be 17.95+/-8.4 micromol/l. Mean concentrations of plasma/serum folate, vitamin B12 and PLP were found to be 5+/-3.9 ng/ml, 522+/-296 pg/ml and 21.6+/-14 nmol/l, respectively. Serum/plasma levels of folate, vitamin B12 and PLP were negatively correlated with plasma homocysteine (rho coefficient=-0.367,

Nature, scope and use of economic evaluation of healthcare programmes: with special reference to Pakistan.

Economic evaluation (EE)/cost effectiveness analysis(CEA) of healthcare programmes is an emerging area, yet the resource base to apprehend EE/CEA is very limited in Pakistan. This paper attempts to fill this gap by providing a basic text in the field of EE with special reference to Pakistan. We used four dimensional criteria (available, relevant, complete and accurate) for reviewing the EE contents in the locally available textbooks and reading material on public health. We find CEA as core competency and skill of medical doctors in undergraduate medical curricula yet we could not find EE contents in the recommended textbooks. We find that economic evaluation entails two rules: both cost and effectiveness should be included in the analysis, and there must be a comparison of at least two drugs or medical intervention. We describe EE/CEA in this article and recommend that EE content should be included in the medical and public health curriculum in Pakistan

A comparison of treatments offered to patients with nonalcoholic steatohepatitis

OBJECTIVE: To compare various treatment options provided to patients with Nonalcoholic Steatohepatitis (NASH) and assess improvement in liver status via reduction in serum Alanine Aminotransferase (ALT) levels. STUDY DESIGN: Retrospective cohort study. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from April 2000 to April 2007. METHODOLOGY: All available records of patients aged between 20-70 years, fatty liver on ultrasound, elevated serum ALT and having at least one follow-up, after a baseline visit were included. The patients had variable number of follow-ups and a maximum of 3 follow-ups were considered. Information was collected on demographic and clinical characteristics of the subjects. The treatment options were categorized as weight reduction alone, with statins, and with other medications. Serum ALT level was the main outcome measured in IU/l. Repeated-measures ANOVA, using a mixed model approach was performed with treatment options as between subject factor, and follow-up as within subject factor and p-value \u3c 0.05 was considered significant. RESULTS: Sixty-nine records of subjects, consisting of 50 males and 19 females were selected. The mean (+/- SD) age was 40+/-12 years. Thirty-one subjects (45%) were advised weight reduction only, and experienced a 72% reduction in serum ALT levels, over the mean follow-up time of 9+/-3 months. Twelve subjects (17%) received statins along with weight reducing advice, and experienced a 56% reduction in mean ALT over the mean follow-up of 11+/-7 months. Twenty-six subjects (38%) received other medications along with advice for weight reduction and experienced a 73% reduction in serum ALT levels over the mean time of 10+/-4 months. The mean ALT declined at follow-up times, irrespective of the prescribed treatment, and that the decline with time was different for males and females. CONCLUSION: Serum ALT levels among patients with NASH decreased with time, regardless of the provided treatment, and the decrease was different for males and females

Pattern of benzodiazepine use in psychiatric outpatients in Pakistan: a cross-sectional survey.

Background: Benzodiazepines (BDZ) are the largest-selling drug group in the world. The potential of dependence with BDZ has been known for almost three decades now. In countries like Pakistan where laws against unlicensed sale of BDZ are not implemented vigorously the risk of misuse of and dependence on these drugs is even higher. Previous studies have shown that BDZ prevalence among Patients/visitors to general outPatient clinics in Pakistan may be as high as 30%. However, no research has been carried out on the prevalence of BDZ use in psychiatric Patients in Pakistan. Methods: We carried out a cross-sectional survey over 3 months in psychiatry outPatient clinics of two tertiary care hospitals in Karachi and Lahore. Besides basic socio-demographic data the participants were asked if they were taking a BDZ at present and if yes, the frequency, route and dosage of the drug, who had initiated the drug and why it had been prescribed. We used chi-square test and t-test to find out which socio-demographic or clinical factors were associated with an increased risk of BDZ use. We used Logistic Regression to find out which variable(s) best predicted the increased likelihood of BDZ use. Results: Out of a total of 419 participants 187 (45%) of the participants had been currently using at least one BDZ. Seventy-three percent of the users had been using the drug for 4 weeks or longer and 87% were taking it every day. In 90% of cases the BDZ had been initiated by a doctor, who was a psychiatrist in 70% of the cases. Female gender, increasing age, living in Lahore, and having seen a psychiatrist before, were associated with an increased likelihood of using BDZ. Conclusion: The study shows how high BDZ use is in psychiatric outPatients in Pakistan. Most of the users were taking it for a duration and with a frequency which puts them at risk of becoming dependent on BDZ. In most of the cases it had been initiated by a doctor. Both Patients and doctors need to be made aware of the risk of dependence associated with the use of BDZ

Improving community case management of diarrhoea and pneumonia in district Badin, Pakistan through a cluster randomised study--the NIGRAAN trial protocol

BACKGROUND: Diarrhoea and pneumonia contribute 30% of deaths in children under 5 in Pakistan. Pakistan\u27s Lady Health Workers Programme (LHW-P) covers about 60% of the population but has had little impact in reducing morbidity and mortality related to these major childhood killers. An external evaluation of the LHW-P suggests that lack of supportive supervision of LHWs by lady health supervisors (LHSs) is a key determinant of this problem. Project NIGRAAN aims to improve knowledge and skills of LHWs and community caregivers through supervisory strategies employed by LHSs. Ultimately, community casemanagement (CCM) of childhood pneumonia and diarrhoea will improve. METHODS/DESIGN: NIGRAAN is a cluster-randomised trial in District Badin, Pakistan. There are approximately 1100 LHWs supervised by 36 LHSs in Badin. For this study, each LHS serves as a cluster. All LHSs working permanently in Badin who regularly conduct and report field visits are eligible. Thirty-four LHSs have been allocated to either intervention or control arms in a ratio of 1:1 through computer-generated simple randomisation technique. Five LHWs from each LHSs are also randomly picked. All 34 LHSs and 170 LHWs will be actively monitored. The intervention consists of training to build LHS knowledge and skills, clinical mentorship and written feedback to LHWs. Pre- and post-intervention assessments of LHSs, LHWs and community caregivers will be conducted via focus group discussions, in-depth interviews, knowledge assessment questionnaires, skill assessment scorecards and household surveys. Primary outcome is improvement in CCM practices of childhood diarrhoea and pneumonia and will be assessed at the cluster level. DISCUSSION: NIGRAAN takes a novel approach to implementation research and explores whether training of LHSs in supervisory skills results in improving the CCM practices of childhood diarrhoea and pneumonia. No significant harm to participants is anticipated. The enablers and barriers towards improved CCM would provide recommendations to policymakers for scale up of this intervention nationally and regionally