HbA1C as a Biomarker of Non-alcoholic Fatty Liver Disease: Comparison with Anthropometric Parameters.

BACKGROUND AND AIMS: Multiple non-invasive methods including radiological, anthropometric and biochemical markers have been reported with variable performance. The present study assessed glycosylated hemoglobin (HbA1C) as a biomarker to predict non-alcoholic fatty liver disease (NAFLD) and its severity, compared with body mass index (BMI), waist to hip ratio (WHR) and waist circumference (WC). METHODS: This case control study included 450 individuals, including 150 cases and 300 age- and gender-matched controls recruited from the Dow Radiology Institute on the basis of radiological findings of fatty infiltration on abdominal ultrasound through convenient sampling. BMI, WHR and WC were measured according to standard protocols. HbA1C was determined by turbidimetric inhibition immunoassay. RESULTS: Among the cases and controls, 66% and 32% had HbA1C levels higher than 5.7% respectively. HbA1C and BMI were significantly associated with NAFLD [crude odds ratio (cOR)=4.12, 2.88, 2.25 (overweight) and 4.32 (obese)]. WC was found to be significantly associated with NAFLD for both genders (cOR in males=5.50 and females=5.79, p<0.01). After adjustment for other parameters, HbA1C and WC were found to be significantly associated with NAFLD (aOR=3.40, p<0.001) along with WC in males (aOR=2.91, p<0.05) and in females (aOR=4.28, p<0.05). A significant rise in severity of hepatic steatosis was noted with increases in HbA1C, BMI and WC. HbA1C possessed a positive predictive value of 76% for the study population [0.76, confidence interval (CI): 0.715-0.809], 70.6% for males (0.706, CI: 0.629-0.783) and 80% for females (0.80, CI: 0.741-0.858). CONCLUSIONS: Higher than normal HbA1C and WC measurements possess a more than 70% potential to predict NAFLD. It is the single risk factor that is strongly associated with NAFLD after adjustment for indices of body measurements. HbA1C may be presented as a potential biomarker for NAFLD in examination with other anthropometric measures in the adult population.

Correction to: Gender Differences and Prevalence of Mental Health Problems in Students of Healthcare Units.

The original version of this article unfortunately contained a typo in the author name. The co-author name should be Ahsan Ehtesham instead it was published as Ahsan Ehtisham.

Gender Differences and Prevalence of Mental Health Problems in Students of Healthcare Units.

The aim of the present was to assess and compare the mental health of male and female healthcare students in a Health University of Karachi, Pakistan. A cross-sectional study was conducted for which questionnaire was designed along the standard scoring scales of depression (PHQ-9), anxiety (GAD-7) and phobia (IAPT) completed by 300 enrolled students. Females (52%) of the medical institute suffered from mild to moderately-severe depression in contrast to the males (33%). Females were found to be affected by mild anxiety and phobia (42.7 and 26% respectively) exceeding the male population (27.3 and 15.3% respectively). However, severe depression or anxiety was not observed in either gender groups significantly, suggesting a healthy mental picture of these medical students. It can be concluded that health care students in modern upgraded education systems, in contrast to evidence from literature, have been able to adopt better coping mechanisms for maintaining their mental health.

False negativity in AFB Smear microscopy: An insight into the caveats of the most widely used screening tool for tuberculosis.

OBJECTIVE: To study the ratio of false negativity in sputum samples in diagnostic smears received for acid fast bacilli smear microscopy. METHODS: The retrospective cross-sectional study was conducted at the Ojha Institute of Chest Diseases, Karachi, and comprised specimens for microscopy and culture from presumptive tuberculosis patients for 38 months starting from November 2010.All laboratory investigations had been done as per the National Tuberculosis Control Programme guidelines. Statistical analyses were performed on MedCalc and Social statistics calculators, and Open Epi software. RESULTS: TOf the 2,158 specimens, 1,316(60.98%) were of men and 842(39.02%) of women (male-to-female ratio: 1.56:1). Besides, 843(39.06%) were smear-negative, of which 99(11.74%) were false negative. Of the 1,275(96.88%) men whose age was reported, 808(63.37%) were aged 19-45 years, whereas out of the 792(94.06) women whose age was known, 517(65.28%) were in that age group. Microscopic outcomes were significantly related to gender (p<0.001). CONCLUSIONS: Smear microscopy cannot be solely relied upon for diagnosis and its results must be correlated with additional clinical information and other diagnostics due to considerable amount of false negativity, especially in female population.

Frequency of Hyperthermia in Acute Ischemic Stroke Patients Visiting a Tertiary Care Hospital.

OBJECTIVE: To determine the frequency of hyperthermia in acute ischemic stroke patients visiting a tertiary care hospital in a developing country. STUDY DESIGN: Cross-sectional, observational study. PLACE AND DURATION OF STUDY: Medical Wards of Civil Hospital, Karachi, from January to June 2013. METHODOLOGY: Patients aged ≥18 years of either gender with acute ischemic stroke presenting within 24 hours of onset of symptoms were included. Written informed consent was obtained from all participants as well as approval of ethical review committee of the institute. Axillary temperature by mercury thermometer was monitored at the time of admission and after every 6 hours for 3 days. The data was analyzed using SPSS version 17.0 (SPSS Inc., IL, Chicago, USA). RESULTS: Atotal of 106 patients of ischemic stroke were included. The mean age of enrolled participants was 60.1 ±9.5 years. Among these, 61 (57.5%) were males and 45 (42.5%) females. Among all patients, 51.9% presented with loss of consciousness, 30.2% with slurred speech, 77.4% with limb weakness, and 9.4% with decrease vision. Atotal of 17 (16%) patients with ischemic stroke developed hyperthermia. When the prevalence of hyperthermia was stratified according to age, among patients of < 60 years of age, 26% developed hyperthermia compared to 7.1% in patients of ≥60 years of age (p=0.008). On gender stratification, among male patients, 14.8% developed hyperthermia compared to 17.8% in female patients (p=0.43). CONCLUSION: It is concluded from this study that the frequency of hyperthermia in ischemic stroke was 16% and it should be looked for as it has significant impact on the outcome. The hyperthermia was significantly more common in younger adults as compared to older adults. However, gender had no influence on the prevalence rate of hyperthermia.

Solitary Rectal Ulcer Syndrome: Demographic, Clinical, Endoscopic and Histological Panorama.

OBJECTIVE: To assess the demographic, clinical, endoscopic and histological spectrum of Solitary Rectal Ulcer Syndrome (SRUS). STUDY DESIGN: Cross-sectional observational study. PLACE AND DURATION OF STUDY: Medical Unit-III, Civil Hospital Karachi (CHK) and Ward 7, Jinnah Postgraduate Medical Centre (JPMC), Karachi, from January 2009 to June 2012. METHODOLOGY: Patients with SRUS, based on characteristic endoscopic and histological findings, were enrolled. Patients were excluded if they had other causes of the rectal lesions (neoplasm, infection, inflammatory bowel disease, and trauma). Endoscopically, lesions were divided on the basis of number (solitary or multiple) and appearance (ulcerative, polypoidal/nodular or erythematous mucosa). Demographic, clinical and endoscopic characteristics of subjects were evaluated. RESULTS: Forty-four patients met the inclusion criteria; 21 (47.7%) were females and 23 (52.3%) were males with overall mean age of 33.73 ±13.28 years. Symptom-wise 41 (93.2%) had bleeding per rectum, 39 (88.6%) had mucous discharge, 34 (77.3%) had straining, 34 (77.3%) had constipation, 32 (72.7%) had tenesmus, 5 (11.4%) had rectal prolapse and 2 (4.5%) had fecal incontinence. Twelve (27.27%) patients presented with hemoglobin less 10 gm/dl, 27 (61.36%) with 10 - 12 gm/dl and 05 (11.36%) subjects had hemoglobin more than 12 gm/dl. Endoscopically, 26 (59.1%) patients had mucosal ulceration, 11 (25.0%) had mucosal ulceration with polypoid characteristics; while only polypoid features were found in 7 (15.9%) subjects. CONCLUSION: Solitary rectal ulcer syndrome affects adults of both genders with diverse clinical presentation and nonspecific endoscopic features.

DIFFERENCES IN CULTURAL YIELD OF MYCOBACTERIUM TUBERCULOSIS ON MEDIA PREPARED USING COMMERCIAL AND HOUSEHOLD EGGS.

BACKGROUND: Mycobacterial culture is considered as the gold standard for TB diagnosis. It is performed on egg-based media using commercially available eggs to grow Mycobacteria from clinical samples. These eggs are known to contain high concentration of antibiotics, including fluoroquinolones, given to chicken to prevent early mortality. This study was performed to compare Mycobacterial growth on media prepared from commercial and antibiotic free household eggs. METHODS: Sputum samples from negative (No bacilli in 100 oil immersion field), scanty (1-9 AFB in 100 fields), 1+ (10-99 bacilli per field), 2+ (1-10 bacilli per field) and 3+ (>10 bacilli per field) were inoculated dually on Ogawa medium prepared from commercial and household eggs. Tubes were inspected every fourth day for the appearance of colonies till 60 days. Data tabulations and statistical analysis (F test for variation and unpaired Student's t test) were performed on Microsoft Excel. RESULTS: One microscopically negative sample showed growth on media prepared from household eggs, while all were negative on that prepared from commercial eggs. There were significant differences in time to culture positivity for samples graded 1+ (p = 0.02), 2+ (p = 0.002) and 3+ (p = 0.0003). CONCLUSION: Commercial eggs containing antibiotics can be a source of false negativity in cultures especially in microscopically negative samples. This can be of special concern in HIV patients who have high smear negativity. It is therefore important to either develop provision of antibiotic free eggs for media preparation or to develop and validate other laboratory investigations for smear negative TB patients.

Interferon-alpha treatment of children and young adults with chronic hepatitis delta virus (HDV) infection.

OBJECTIVE: To determine the response of one-year interferon-alpha therapy in hepatitis delta virus (HDV) infection in children and young adults at a tertiary care hospital, Karachi, Pakistan. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Sarwar Zuberi Liver Centre (SZLC), Medical Unit IV, Civil Hospital, Karachi/Dow University of Health Sciences (DUHS), from June 2009 to July 2010. METHODOLOGY: Paediatric patients (< 18 years age) and young adults (18-35 years) presenting were screened for hepatitis B virus (HBV) and HDV sero-markers. HDV anti-body positive by ELISA were further screened for hepatitis D ribonucleic acid (HDV-RNA) by real time PCR. HDV RNA PCR positive patients were treated with INF-a (children 6 MIU/m2/day and adults 5 MIU/day) for a period of one year. Patients were assessed monthly. Haematological parameters and ALT were monitored during treatment. Clinical progress (side effects) and negative HDV RNA were used as response criteria. RESULTS: Overall 49 patients were HDV RNA positive (children: n=15, mean age 15±2.92 years adults: n=34, mean age 27±4 years). Eighty percent were male. Treatment was given to 25 patients (children: n=11, adults: n=14). HBV genotype D was the predominant in all HDV RNA positive patients (73%). Eighty percent (20/25) were HDV-RNA negative after one year of treatment, and remaining patients are still under treatment. Side effects were tolerated well and children continued regular activity. Haematological parameters were unremarkable. Children maintained their pre-treatment centile for height and weight (growth parameters). ALT levels were significantly decreased post-treatment. CONCLUSION: Conventional INF-a was safe in children with HDV infection in terms of side effects and growth parameters. Eighty percent were HDV-RNA negative one year after treatment. Further follow-up 2 years post-treatment will give conclusive results.

Treatment profile of hepatitis C patients - a comparison of interferon alpha 2a and 2b treatment regimes.

OBJECTIVE: To compare the side effects, cost, end treatment response (ETR) and Sustained viral response (SVR) with combination therapy of either interferon alpha 2a or 2b in combination with Ribavarin. STUDY DESIGN: Randomized Control Clinical Trial (RCCT). PLACE AND DURATION OF STUDY: The study was conducted at Sarwar Zuberi Liver Centre (SZLC), Civil Hospital Karachi (CHK), from May 2004 to July 2009. METHODOLOGY: Patients positive for qualitative HCV ribonucleic acid (RNA) by Polymerase chain reaction (PCR) and genotype 3 were included. Patients with decompensated cirrhosis, severe depressive illness, autoimmune hepatitis, hyperthyroidism, pregnancy, heart failure, uncontrolled diabetes, obstructive pulmonary disease, children less than three years and patients who had previously received treatment were excluded. Single blind randomization using computerized randomization list was done and patients divided into groups A and B, those requiring treatment were given injection Interferon 3 million units (MU) subcutaneously (SC) three times/week and Ribavarin 1000 mg per day (weight ≤ 75kg) and 1200 mg/day (weight > 75kg) orally with either interferon alpha 2a (group A; FDA approved products) or alpha 2b (group B; non FDA approved product). Demographics, side effects, ETR and SVR were noted. ETR was defined as absence of virus at the end of treatment and SVR was taken as absence of HCV RNA at 6 months after completion of treatment. RESULTS: There were a total 310 patients with mean age of 34.07 +/- 9.38 years including 52.4% males, (n=162). Majority of the patients were from North Pakistan. There were 155 patients each in group A and group B respectively. The cost of treatment for interferon alpha for a single patient for 6 months was Rs 60,000, while for Interferon alpha 2b was Rs 30,000. Side effects (fever initially, followed by fatigue, headache, musculoskeletal pain, depression, alopecia, insomnia, and anorexia) were more prominent in group B when compared with group A. In group A, ETR was 83.8% (130/155) while in group B was 83.2% (129/155). While SVR available in group A was 61/70 (87.1%) and in group B was 60/72 (83.3%). CONCLUSION: Response to combination therapy for HCV was 83%. ETR and SVR were similar for both interferon alpha 2a and 2b. Side effects though minor are more with alpha 2b (non FDA approved products).

Multiple diverse circoviruses infect farm animals and are commonly found in human and chimpanzee feces.

Circoviruses are known to infect birds and pigs and can cause a wide range of severe symptoms with significant economic impact. Using viral metagenomics, we identified circovirus-like DNA sequences and characterized 15 circular viral DNA genomes in stool samples from humans in Pakistan, Nigeria, Tunisia, and the United States and from wild chimpanzees. Distinct genomic features and phylogenetic analysis indicate that some viral genomes were part of a previously unrecognized genus in the Circoviridae family we tentatively named "Cyclovirus" whose genetic diversity is comparable to that of all the known species in the Circovirus genus. Circoviridae detection in the stools of U.S. adults was limited to porcine circoviruses which were also found in most U.S. pork products. To determine whether the divergent cycloviruses found in non-U.S. human stools were of dietary origin, we genetically compared them to the cycloviruses in muscle tissue samples of commonly eaten farm animals in Pakistan and Nigeria. Limited genetic overlap between cycloviruses in human stool samples and local cow, goat, sheep, camel, and chicken meat samples indicated that the majority of the 25 Cyclovirus species identified might be human viruses. We show that the genetic diversity of small circular DNA viral genomes in various mammals, including humans, is significantly larger than previously recognized, and frequent exposure through meat consumption and contact with animal or human feces provides ample opportunities for cyclovirus transmission. Determining the role of cycloviruses, found in 7 to 17% of non-U.S. human stools and 3 to 55% of non-U.S. meat samples tested, in both human and animal diseases is now facilitated by knowledge of their genomes.

Self-reported practices of hand hygiene among the trainees of a teaching hospital in a resource limited country.

OBJECTIVE: To determine the compliance of hand hygiene among the trainee physicians of a tertiary care teaching hospital; and to identify physicians' opinion regarding various obstacles in adhering to the hand hygiene principles. METHODS: Cross-sectional survey was conducted among the Interns (House Officers) and Post Graduate trainee physicians of a tertiary care teaching hospital in a resource limited country. Subjects were consented and selected through non probability convenient sampling. A self-administered questionnaire, based on the hand hygiene guidelines laid down by the World Health Organization (WHO) was used. RESULTS: A total of 211 questionnaires were completed. Only 4.7% of the physicians reported to decontaminate their hands before having direct contact with their patients. Only 17% claimed to be aware of the WHO recommendations on hand hygiene. Majority of subjects considered "lack of sinks, soap, water and disposable towel" as a major barrier towards hand hygiene adherence. Overall compliance of hand hygiene was found to be 38.8% but it widely varied as a function of patient care activity. CONCLUSION: Hand hygiene practices among trainee physicians were not in line with WHO recommendations. To make a difference, interventions taken to improve awareness alone, won't be sufficient; they have to be supported with improving facilities for hand hygiene.

Epidemiology and clinical findings associated with enteroviral acute flaccid paralysis in Pakistan.

BACKGROUND: Enteroviruses are among the most common viruses infecting humans worldwide and they are associated with diverse clinical syndromes. Acute flaccid paralysis (AFP) is a clinical manifestation of enteroviral neuropathy, transverse myelitis, Guillian-Barre Syndrome, Traumatic neuritis and many other nervous system disorders. The objective of this study was to understand the role of Non-Polio Enteroviruses (NPEV) towards this crippling disorder. METHODS: Stool specimens of 1775 children, aged less than 15 years, suffering from acute flaccid paralysis were collected after informed consent within 14 days of onset of symptoms during January 2003 to September 2003. The specimens were inoculated on RD and L20B cells using conventional tube cell culture while micro-neutralization test was used to identify the non-polio enterovirus (NPEV) serotypes. Detailed clinical information and 60-days follow-up reports were analyzed for NPEV-associated AFP cases. RESULTS: NPEV were isolated from 474 samples. The male to female ratio was 1.4:1. The isolation of NPEV decreased significantly with the increase in age. Cases associated with fever at the onset of NPEV-associated AFP were found to be 62%. The paralysis was found asymmetrical in 67% cases, the progression of paralysis to peak within 4 days was found in 72% cases and residual paralysis after 60 days of paralysis onset was observed in 39% cases associated with NPEV. A clinical diagnosis of Guillian-Barre syndrome was made in 32% cases. On Microneutralization assay, echo-6 (13%) and coxsackievirus B (13%) were the most commonly isolated serotypes of NPEV along with E-7, E-13, E-11, E-4 and E-30. The isolates (n = 181) found untypable by the antiserum pools were confirmed as NPEV by PCR using Pan-Enterovirus primers. CONCLUSION: The present study suggests that NPEV are a dominant cause of AFP and different serotypes of NPEV are randomly distributed in Pakistan. The untypable isolates need further characterization and analysis in order to determine their association with clinical presentation of a case.