Difference in memory recall among medical students after reading printed text (hard copy) vs. on screen text (soft copy).

OBJECTIVE: To compare the difference in "memory recall" among undergraduates (UGs) and postgraduates (PGs) medical students reading printed text (hard copy) vs. on-screen text (soft copy). METHODS: Final year UGs medical students (Group A) were divided into two batches, one batch was given hard copy of 1258 worded text and other group was given a soft copy of the same text. Likewise PGs (Group B) were divided into two batches, each batch was given hard copy and soft copy of the same text material with identical physical attributes. All batches were asked to read the text in 15 minutes. Text was then removed and a proforma containing statements pertaining to recall of the text material was administered to all. RESULTS: The scores of students reading soft copy text were significantly higher compared to student reading text from hard copy (p<.008) in the proforma assessing memory recall. CONCLUSIONS: The memory recall from reading on screen text is better than reading printed (paper) text, implying that with the advancement of technology and early exposure to computer screen, students are developing the habit of reading on screen text more conveniently.

Antibody-Secreting Cells To Diagnose Mycobacterium tuberculosis Infection in Children in Pakistan.

Reliance on microbiologic methods to diagnose Mycobacterium tuberculosis infection is a suboptimal approach for children due in part to the paucibacillary nature of the disease. A blood-based biomarker assay, such as the mycobacterial-antibody-secreting cell (MASC) assay, could be a major advance for the field of study of pediatric tuberculosis (TB). Children <15 years of age with clinical concern for TB and age-matched children with no concern for TB were enrolled from outpatient clinics in Karachi, Pakistan. MASC, ferritin, and C-reactive protein (CRP) assays were performed, and results were compared among cases and controls, as well as among children with a case definition of "confirmed TB," "probable TB," or "possible TB." MASC responses were significantly higher among children with TB than among controls (0.41 optical density [OD] versus 0.28 OD, respectively, P < 0.001), and the differences were largely driven by the data from children with confirmed TB (P = 0.002). Ferritin and CRP values were significantly higher among those with confirmed TB than among those with the other disease states and controls (P = 0.004 and P = 0.019, respectively). The use of the MASC assay as a blood-based biomarker for TB disease shows some promise among children with microbiologically confirmed disease; however, the performance characteristics for the majority of young children with unconfirmed TB were suboptimal in this cohort.IMPORTANCE Tuberculosis (TB) in children represents a missed opportunity for diagnosis and preventive therapy. The magnitude or burden of disease in children is not fully understood due to our limitations with respect to exploring sensitive diagnostic algorithms. In a setting of TB endemicity in Pakistan, we carried out a proof-of-concept study to evaluate for the first time the performance of B cell analyses by the use of well-defined diagnostic criteria and NIH consensus guidelines as "culture-confirmed," "probable," and "possible" TB groups. In contrast to detection of serum antibody, we focused on mycobacterial-antibody-secreting cell (MASC) detection as a marker of active disease in children with a strong suspicion of TB. Further work exploring a larger panel of inflammatory biomarkers and enrichment of B cells with the objective of increasing the sensitivity of the current MASC assay would lead to the development of a field-friendly assay for timely diagnosis of childhood TB.

Exome sequencing identifies a novel frameshift variant causing hypomagnesemia with secondary hypocalcemia.

Hypomagnesemia with secondary hypocalcemia is a rare autosomal-recessive disorder characterized by intense hypomagnesemia associated with hypocalcemia (HSH). Mutations in the TRPM6 gene, encoding the epithelial Mg2+ channel TRPM6, have been proven to be the molecular cause of this disease. This study identified causal mutations in a 2-month-old male patient of hypomagnesemia from a consanguineous marriage. Biochemical analyses indicated the diagnosis of HSH due to primary gastrointestinal loss of magnesium. Whole exome sequencing of the trio (i.e. proband and both parents) was carried out with mean coverage of > 150×. ANNOVAR was used to annotate functional consequences of genetic variation from exome sequencing data. After variant filtering and annotation, a number of single nucleotide variants (SNVs) and 2 bp deletion at exon26:c.4402_4403delCT in TRPM6 gene were identified. This deletion which resulted in a novel frameshift mutation in exon 26 of this gene was confirmed by Sanger sequencing. With these investigations in hand, the patient was managed with magnesium sulphate. The patient remained asymptomatic and was developmentally and neurologically normal till his last follow up.

Evaluation of Xpert MTB/RIF testing for rapid diagnosis of childhood pulmonary tuberculosis in children by Xpert MTB/RIF testing of stool samples in a low resource setting.

OBJECTIVE: Children with tuberculosis (TB) remain underdiagnosed due to difficulty in testing for Mycobacterium tuberculosis (MTB) infection. We evaluated the Xpert MTB/RIF assay for respiratory and stool testing in children for pulmonary TB through a cross-sectional study at tertiary care facilities in Karachi, Pakistan. Fifty children aged 0-15 years screened by a modified Kenneth-Jones (KJ) score were included. Mycobacterial culture of respiratory samples was the microbiological standard against stool Xpert TB results. All positive TB cases were compared against a treatment response standard (TRS). RESULTS: Twelve study subjects were diagnosed by Xpert TB and nine by MTB culture. Compared with culture [gastric aspirates (GA)/sputum (spm)], stool Xpert TB had a sensitivity of 88.9% (95% CI 50.7-99.4) and a specificity of 95% (95% CI 81.8-99.1). Xpert TB stool versus GA/spm had sensitivity of 81.8% (95% CI 47.8-96.8) and specificity of 94.7% (95% CI 84.6-99.9). We found good agreement (kappa scores of >0.8) between stool Xpert, GA/spm Xpert and GA/spm culture. Stool Xpert PPV and NPV against TRS was 100 and 82.1% respectively. Stool Xpert TB is a relatively easy option for diagnosis for pulmonary childhood TB in a high burden low-resource setting.

Effective testing for pulmonary tuberculosis using Xpert MTB/RIF assay for stool specimens in immunocompetent Pakistani children.

OBJECTIVE/BACKGROUND: Childhood tuberculosis (TB) is largely a paucibacillary disease and difficult to diagnose. It is difficult to obtain a sputum or gastric aspirate (GA) sample, and patients are often undiagnosed and treated empirically. Stool is a noninvasive specimen not usually used for TB testing in Pakistan. We investigated the value of Xpert MTB/RIF to diagnose Mycobacterium tuberculosis (MTB) in children with pulmonary TB cases, by performing comparative testing of GA and stool samples. METHOD: We recruited 60 children aged 1-15years, suspected of TB, from the Department of Pediatrics, Civil Hospital, Karachi, Pakistan and The Aga Khan University Hospital, Karachi, Pakistan. All were immunocompetent. Patients had a Kenneth Jones TB score of ⩾5. Paired GA/sputum and stool samples were collected for testing. All GA samples were tested by Xpert MTB/RIF assay and MTB culture, while stool was tested by Xpert MTB/RIF. RESULTS: The study participants included 27 males and 23 females with a mean age of 6years and a mean TB (Kenneth Jones) score of 7. Stool was received in the laboratory within 1-2days of the GA sample for all but one participant, who expired. The rates of MTB detection were as follows: 22% (11 cases) based on Xpert MTB testing of GA, 21% (10 cases) based on MTB culture of GA, and 21% (10 cases) based on Xpert MTB testing of stool. No rifampicin resistance was detected. Overall, there was concordance between testing of GA and stool. One case had GA with low positive Xpert and positive MTB culture, but negative stool Xpert result. In another case, there was low positive GA Xpert, positive GA MTB culture, and positive stool Xpert. A positive Xpert MTB stool test was associated with a higher TB score (>5) and a greater bacillary load. All 11 cases of TB diagnosed were put on antituberculous therapy and responded well to treatment. CONCLUSION: Use of Xpert MTB/RIF assay for stool-based diagnosis of pulmonary TB in immunocompetent children is useful in a resource poor setting. This is a valuable and noninvasive diagnostic alternative for the diagnosis of childhood TB and can be adapted by pediatric arms of national TB programs.

Implementing WHO feeding guidelines for inpatient management of malnourished children.

OBJECTIVE: To evaluate the efficacy of adopting WHO feeding guidelines on weight gain and case fatality rate in malnourished children. STUDY DESIGN: Cross-sectional, observational study. PLACE AND DURATION OF STUDY: Department of Pediatrics, Dow University of Health Sciences, Karachi, from 2009 to 2010. METHODOLOGY: Patients above 6 months and less than 5 years of age with severe malnutrition were included during the study period, acute complications were treated and nutritional rehabilitation by WHO feeding formulae was done. Demographic details, clinical features, reasons for weight gain and risk factors of mortality were analyzed. RESULTS: A total of 131 children were included. Mean age of children was 22 ± 18 months. There were 78% marasmic, 4% kwashiorkor and marasmic kwashiorkor 18% children. Resolution of edema took 8 ± 4 days, dermatosis cleared in 11 ± 3 days. Mean hospital stay was 10 ± 8 days. Case fatality rate was 13%. Mean weight gain was 5.25 ± 4.57 g/kg/day. Weight gain of > 5 gm/kg/day was associated with hospital stay of more than 7 days, acceptability and palatability of feed by the children and mothers and early clearance of infections. CONCLUSION: Implementation of WHO feeding guidelines resulted in adequate weight gain of inpatient malnourished children, however, adequate healthcare services are available at the therapeutic feeding centers.

Psychosocial determinants of nutritional neglect in a developing country.

OBJECTIVE: To determine the demographic features and psycho-social and economic determinants of nutritional neglect in order to suggest interventional strategies. STUDY DESIGN: Cross-sectional, observational study. PLACE AND DURATION OF STUDY: Department of Paediatrics, Dow University of Health Sciences (DUHS) and Civil Hospital Karachi (CHK), from January 2009 to December 2010. METHODOLOGY: All children suffering from nutritional neglect suggested by weight and height less than the third centile for age, and their mothers were recruited in the study through non-probability consecutive sampling. A team comprising of paediatrician, psychologist, medical social worker and social motivator interviewed the mothers and children suffering from nutritional neglect. Information about demographic, social, economic and psychological factors was obtained. The results were analyzed and described as frequency distribution and percentage. RESULTS: A total of 658 children suffering from nutritional neglect were inducted. Around 75% of children were below 5 years of age, 51% were females. Other determinants of nutritional neglect were, large family size (family of > 5 members (84%), young mother (60%), uneducated parents (67% father and 77% mothers being illiterate), low income (77% earning less than Rs. 7000/month), addiction (23%), tobacco smoking (50%) and non-nutritive substance use (51%). Psychological indicators identified in mothers were depression (70%), anxiety (73%), helplessness (70%), displaced aggression (50%) and insecurity (36%). Psychological factors identified in children as a secondary outcome were aggression (80%), rebellious behaviour (75%), lack of confidence (70%), lack of social interaction (70%) and paranoid tendencies (60%). CONCLUSION: Psycho-social and economic factors are important determinants of neglect. A holistic approach and intervention at multiple levels is required to address these issues.

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.

Applicability of scoring chart in the early detection of tuberculosis in children.

OBJECTIVE: To test the applicability of scoring chart to detect children suffering from tuberculosis. DESIGN: Case control study. PLACE AND DURATION OF STUDY: The study was conducted at the Department of Paediatrics Unit-1, Civil Hospital, Karachi. SUBJECT AND METHODS: Included in this study were 50 children in whom tuberculosis (TB) was diagnosed on the basis of history, physical signs, investigations and positive response to anti-tuberculous therapy. Also included in the study were 50 controls admitted with diagnosis other than tuberculosis. Modified Kenneth Jones Scoring Chart (KJSC) was applied to both the groups of children. These children were given a score of 0-7 or above according to the chart. The sensitivity of various parameters used in the KJSC was also tested in both the groups. RESULTS: A score of 1-2 (TB unlikely) was found in none of the cases versus 44% in the controls. Score of 5-6 (TB probable) was obtained in 40% of cases and none in the controls. Fifty-six percent cases had a score of 7 or more (TB unquestionable) versus 0% in controls. Contact with an adult suffering from tuberculosis, physical and radiological signs suggestive of tuberculosis and an exaggerated reaction to BCG vaccine emerged as the most important indicators used in the scoring chart to detect children with tuberculosis. CONCLUSION: The Kenneth Jones Scoring Chart is a simple cost-effective tool, which can easily be applied to improve the case detection rate in children. In the absence of a gold standard for diagnosing tuberculosis in children and in view of logistic and financial constraints faced by resource constraint countries, like ours, this simple screening tool can be utilized at the health care facilities.