Usefulness Of Sofosbuvir And Daclatasvir Combination In The Treatment Of HCV Infection In Childhood Cancer Patients: Experience From A Tertiary Care Hospital.

Objectives: To determine the usefulness of Sofosbuvir-Daclatasvir combination in the treatment of hepatitis c virus infection in paediatric cancer.. METHODS: The retrospective study was conducted at the Oncology Department of the National Institute of Child Health, Karachi, and comprised medical charts of patients who received sofosbuvir and daclatasvir from January 2018 to January 2022. Efficacy was documented by clearance of hepatitis C virus ribonucleic acid as rapid viral response, early viral response and sustained viral response at weeks 4, 12 and 24, respectively. Drug efficacy was determined by monitoring and recording adverse effects. Chemotherapy protocol for the treatment of patients concomitantly receiving direct acting antivirals was modified while looking at drug-drug interactions. The total duration of direct acting antiviral therapy was 12 weeks. Data was analysed using SPSS 24. RESULTS: Of the 804 patients with different malignancies, 132(16.4%) were found positive for hepatitis C virus. Of them, 28(21.21%) patients were started on direct acting antivirals; 17(60.71%) boys and 11(39.28%) girls. The overall mean age was 9.93±6.12 years. The diagnosis was pre-B acute lymphoblastic leukaemia in 18(64.28%) cases, 16 (57.14%) were on maintenance chemotherapy, and 18(64.28%) had genotype 1. Pre- and post-treatment mean alanine transaminase levels were 328.00±324.00IU and 36.00±29.00IU, respectively (p=0.003). Pre- and post- treatment mean serum bilirubin levels were 3.13±3.95mg/dl and 0.61±0.21mg/dl (p=0.022). Rapid viral response was achieved in 26(92.85%) children, while early viral response and sustained viral response were achieved in all 28(100%) patients. Minor side effects were noted in 4(14.28%) patients and chemotherapy was continued in all 28(100%) cases as per the designed protocol. CONCLUSIONS: The sofosbuvir-daclatasvir combination was found to be effective in hepatitis C virus treatment in paediatric cancer patients.

Changes in caloric consumption, physical activity, body mass index and sleeping pattern during holy month of Ramadan among doctors of a public sector University.

Objectives: To determine the change in caloric intake, physical activity, body mass index and sleeping pattern during Ramadan among doctors. METHODS: The longitudinal study was conducted at a public-sector medical university in Karachi from April to May 2020, and comprised healthy doctors of either gender who planned to fast during Ramadan. Data was collected using a multitude of validated structured tools by trained data collectors. Data was analysed using SPSS 20. RESULTS: Of the 193 subjects, 103(53.4%) were females and 90(46.6%) were males. The overall mean age was 30.05±9.4 years. Caloric intake in the month before Ramadan was significantly higher 2288±495kcal/day than during Ramadan 2089±491kcal/day (p<0.001). Calories from proteins decreased and those from fats increased (p<0.001). Metabolic equivalent of task per minute per week increased significantly during Ramadan (p<0.001). Overall sleep per day decreased significantly, and there was an increase in daytime sleep and a decrease in night-time sleep (p<0.05). Body mass index also dropped significantly (p=0.005). CONCLUSIONS: Fasting during Ramadan had a positive effect on body mass index and physical activity levels of doctors, while the quality of diet and sleep was affected negatively.

Effectiveness And Safety Of Direct Acting Antiviral Agents In Thalassaemic Patients With Chronic Hepatitis C.

BACKGROUND: Pakistan has the highest prevalence of Β-Thalassemia major in children and Chronic Hepatitis C (HCV) infection is a common transfusion transmitted infection. After the emergence of new generations of Antiviral drugs labelled as Direct Acting Antivirals (DAAs), substantial eradication of HCV has been reported as 90-95% with fewer side effects as compared to older regimen of Peginterferon with or without Ribavirin. The main objective of this study was to assess the Rapid virological response (RVR) at 4th week, End of treatment response (ETR) at 12th week and sustained viral response (SVR) at 24th week achieved by using direct acting antiviral and to assess their safety. Methods: Retrospective descriptive study was conducted from July 2018 to July 2020 at National Institute of Child Health. All ß-thalassemia major paediatric patients with HCV infection and age between 3-14 years were included. Demographic data, liver function test, HCV PCR, and response of antiviral therapy was recorded and analyzed. Safety was determined by adverse effects reported in records and efficacy was documented by clearance of HCV-RNA to see ETR and SVR. RESULTS: Total 21 patients were treated. Mean age was 7.67±3yr and 12 (57%) were male. Mean weight was 19.3±3.2kg. RVR and ETR was achieved in all (100%) and SVR was achieved in 20/21 (95%) patients. Headache in 2(9.5%) and generalized body ache was found in 1 (4.25%) patient. Conclusion: Combined Sofosbuvir and Daclatasvir were found to be effective and safe for treating HCV in Thalassaemia Major Children.

Etiology in Children Presented With Chronic Liver Disease in a Tertiary Care Hospital.

Background Chronic liver disease (CLD) is one of the most significant causes of morbidity and mortality among the pediatric age group. The identification of the etiology of the disease is of utmost importance for the effective management of the disease. Objective To determine the various causes of CLD in pediatric patients attending a large public sector pediatric hospital. Patients and methods A prospective cross-sectional study was conducted at the National Institute of Child Health, Karachi, Pakistan from August 1, 2021, to February 28, 2022. All patients below 16 years of age of either gender with more than three months of symptoms duration on admission were enrolled. The diagnosis was labeled after the standard reference ranges for the pediatric age group. Results Of 136 patients, the mean age was 4.42 ± 3.92 years. More than half of the patients were males (76, 55.9%). Hepatitis B (31, 22.8%), idiopathic (23, 16.9%), glycogen storage disorder (GSD) (21, 15.4%), and Wilson disease (14, 10.3%) were the most common cause of CLD. A significant association of hepatitis was observed with age (p-value < 0.001), residence (p-value = 0.048), symptomatic (p-value < 0.001), total bilirubin level (p-value = 0.003), direct bilirubin level (p-value = 0.002), and albumin level (p-value = 0.003). Whereas a significant association of GSD was observed with age (p-value = 0.001), residence (p-value < 0.001), and serum glutamic pyruvic transaminase (SGPT) level (p-value = 0.033). Conclusion In our cohort, hepatitis B, idiopathic, GSD, and Wilson disease were the most common causes of CLD in pediatric patients. Moreover, age, residence, symptomatic, total bilirubin level, direct bilirubin level, SGPT, and albumin level were the important predictor variables.

Effectiveness of Ready-to-Use Therapeutic Food Among Children With Protein-Calorie Malnutrition.

Background Malnutrition develops when there is an inadequacy of one or more than one macronutrient for optimum body functioning. This study was designed to determine the effectiveness of ready-to-use therapeutic food (RUTF) in children with protein-calorie malnutrition (PCM) in terms of weight gain and mid-upper arm circumference (MUAC) improvement. Methodology This prospective observational study was done at The Department of Pediatrics, National Institute of Child Health, Karachi, Pakistan from 1st January 2021 to 31st December 2021. A total of 159 children of either gender between six and 59 months of age and diagnosed with PCM were included. All children participating in the study were asked to come back for a follow-up every two weeks until they are 12 weeks old. Outcomes were measured in terms of comparison of weight gain and MUAC at baseline and after 12 weeks of RUTF. Results Of the 159 children, 94 (59.1%) were female. The mean age was 16.8±9.2 months, and 88 (55.3%) children were aged between six to 12 months. The mean body weight was 6.8±9.7 kg. The mean MUAC was calculated to be 116±9.1 mm. There were 121 (76.1%) children who had severe acute malnutrition. One hundred and thirty-one children completed the planned 12-week of follow-up using RUTF in this study, so they were included in the final analysis. Body weight increased significantly from baseline to 12-weeks after RUTF (6.8±1.7 kg vs. 7.6±1.2kg, p<0.0001). Likewise, MUAC also increased from baseline to 12 weeks after RUTF (116.0±9.1 mm vs. 127.2±8.2 mm, p<0.0001). Conclusion The RUTF was found to significantly improve weight gain and MUAC among children aged between six to 60 months with PCM during a period of 12-weeks. Early diagnosis and timely intervention can improve outcomes among children with PCM. Community-based interventions can be aimed to improve the nutritional status of children in a developing country like Pakistan.

Trends in Weight Gain Among Breastfed Infants Versus Bottle-Fed Infants at a Tertiary Care Hospital in Karachi, Pakistan.

Background Infants need to be exclusively breastfed up to six months of age, and breastfeeding should be continued up to two years of age along with complementary food. In Pakistan, the majority of newborns are not exclusively breastfed. This study was done to compare weight gain between breastfed infants and non-breastfed infants at a tertiary care hospital in Karachi, Pakistan. Methodology This observational cohort study was conducted at the well-baby clinic and vaccination center of the National Institute of Child Health, Karachi, Pakistan, from January 2021 to December 2021. A total of 360 normal term babies (180 in each group) with age below 11 months on either exclusively breastfeeding or other milk feed were included. Data were collected by the duty senior staff nurse of the well-baby clinic and monitored on daily basis by the researchers. The sociodemographic characteristics of mothers of breastfed and non-breastfed babies and birth weight, length, and BMI Z scores of babies in both groups were compared. Results In a total of 360 babies, there were 192 (53.3%) boys and 168 (46.7%) girls. Overall, the mean maternal age was calculated to be 28.1±6.2 years, ranging between 18 and 37 years. The employment status of mothers (p=0.0117) and monthly income of parents (p=0.0388) were significantly different between groups. The mean weight gain in the exclusively breastfeeding group was 4.0±0.5 kg between the first and fifth visit (final visit) in comparison with 4.5±0.5 kg in the non-breastfeeding group (p<0.0001). Conclusion Non-breastfed babies gained significantly more weight in comparison with exclusively breastfed babies. More multicenter trials involving a large proportion of populations are needed to further verify the findings of the present study.

Congenital hepatic fibrosis: clinical presentation, laboratory features and management at a tertiary care hospital of Lahore.

OBJECTIVE: To describe the clinical presentations, laboratory features and management of congenital hepatic fibrosis patients at a tertiary care hospital. METHODS: The case series was conducted at The Children Hospital and Institute of Child Health, Lahore, Pakistan, from July 2013 to June 2015, and comprised patients of congenital hepatic fibrosis diagnosed on the basis of liver biopsy. SPSS 20 was used for statistical analysis. RESULTS: The mean age of 25 patients in the study was 8.5±2.74 years, and the male-to-female ratio was 3:1. Parents of 21(84%) patients had consanguineous marriage, and 14(56%) patients had family history of hematemesis and melena. Besides, 15(60%) patients presented with hematemesis, 12(48%) had abdominal distension, 5(20%) were picked up on screening of siblings and 5(20%) were referred from general practitioners on feeling of hepatosplenomegaly during routine examination. All had hepatomegaly with a mean size of 7.2 ±2.3cm palpable in midline. Splenomegaly was present in 24(96%). Overall, 15(60%) patients had oesophageal varices. Endoscopic band ligations were done in oesophageal variceal patients who were successfully managed, while 5(20%) patients required portosystemic shunt surgeries. CONCLUSIONS: Congenital hepatic fibrosis was not uncommon in our population having high rate of consanguinity and most of them were familial cases.

Spectrum of Inherited Metabolic Disorders in Pakistani Children Presenting at a Tertiary Care Centre.

OBJECTIVE: To determine the frequency, presentation and outcome of various inherited metabolic diseases in children presenting in a tertiary care hospital, Lahore, Pakistan. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Gastroenterology, Hepatology and Nutrition Department of The Children Hospital and Institute of Child Health, Lahore, from January 2011 to October 2014. METHODOLOGY: All children aged < 14 years with high suspicion of a metabolic disorder were inducted. Routine and radiological investigation were carried out at the study place. Comprehensive diagnostic testing of particular metabolic disorder was sent abroad. Those with a specific metabolic disorder were included in the study while those with normal metabolic work-up were excluded. All data was collected on preformed proforma. RESULTS: Atotal of 239 patients were enrolled. Nineteen different types of inherited metabolic disorders were diagnosed in 180 patients; age ranged from 8 days to 14 years. Consanguinity was positive in 175 (97%) among the parents of the affected children, with previously affected siblings in 64 (35.5%). The most frequent disorders were inherited disorders of carbohydrate metabolism (92, 51%), lipid storage disease (59, 32.7%), organic acidemia and energy defects (18, 10%), amino acid disorder (6, 3.3%), and miscellaneous (4, 2.2%). Fifty-eight (32.2%) presented with acute metabolic crisis, 28 (15.5%) patients presented with early onset liver failure, and 24 (13.3%) with mental retardation. Out of these, 16 (8.8%) expired. CONCLUSION: Glycogen storage disorders being the commonest followed by Gaucher disease and Galactosemia. The associated complications resulted in high morbidity and mortality.

Response to nebulized salbutamol versus combination with ipratropium bromide in children with acute severe asthma.

OBJECTIVE: To compare the efficacy of nebulised salbutamol alone and in combination with ipratropium bromide in acute severe asthma in children. METHODS: The randomised controlled trial was conducted at the National Institute of Child Health, Karachi, from October 2012 to March 2013, and comprised patients with acute severe asthma who were randomised into two equal groups. Group A patients received 3 doses of nebulised salbutamol alone (0.03 ml/kg/dose) at 15-minute intervals and Group B received 3 similar doses of salbutamol along with ipratropium (250 ug/dose). Acute severe asthma was categorised as serve exacerbation (clinical score >10) and moderate (5-10 score) based on Bentur Modification. Efficacy was measured after 5minutes of the last dose by change in severity score from severe exacerbation (baseline) to low score. SPSS 10 was used for statistical analysis. RESULTS: There were two groups of 100(50%) patients each. The mean age in Group A was 9.1±3 years and 9.3±2.8 years in Group B. Male-Female ratio in Group A was 1.5:1 and in Group B it was 1.2:1. In Group B, 93(93%) children showed improvement in clinical score (<10 score) while it was 84(84%) in Group A. There was better response in clinical score in Group A than Group B, but it was not significant (p>0.05). CONCLUSIONS: The combination of nebulised salbutamol along with ipratropium bromide in the treatment of acute asthma exacerbation was not superior to salbutamol alone.

Permanent Neonatal Diabetes (DEND Syndrome).

DEND syndrome is a very rare syndrome of permanent neonatal diabetes mellitus, with an incidence of < 1/1000,000. It is defined as a triad of developmental delay, epilepsy, and neonatal diabetes. We report the case of a 9-month infant girl who presented with the most severe form of neonatal diabetes mellitus spectrum along with developmental delay and epilepsy. Genetic mutation testing confirmed mutations in KCNJ11 gene encoding the Kir6.2 subunit of the K-ATPchannel, which are involved in insulin secretion. The use of oral sulfonylureas in treatment of such patients is showing promising results worldwide. The authors strongly recommend early referral and checking for genetic mutations in all patients of neonatal diabetes mellitus.

Spontaneous Perforation Of Bile Duct, Clinical Presentation, Laboratory Work Up, Treatment And Outcome.

BACKGROUND: Spontaneous perforation of bile duct (SPBD) is a rare and often misdiagnosed entity. Though rare, it is the second most common surgical cause of jaundice in infants, after biliary atresia. This study was planned to determine the clinical presentation, study different diagnostic modalities, treatment and outcome of patients with spontaneous perforation of bile duct. METHODS: This descriptive case series, comprising 22 patients with spontaneous perforation of bile duct over a period of 24 months. Clinical presentation, biochemical abnormalities, imaging details, treatment options and outcome were studied. RESULTS: Total 22 patients (12 Males and 10 Females) between ages of 1.5-36 months were studied. Associated anatomical defects included choledochal cyst in 7 (31.8%) while acquired biliary atresia in 1 (4.5%). Elevated liver enzymes (ALT and AST) were present in 16 patients (72.7%) and 5 (22.7%) had bilirubin above 3 mg/dl. Coagulopathy was seen in 8 (36.6%) patients. Abdominal USG showed presence of ascites in all 22 (100%), hydrocele in 2 (9.0%), inguinal hernia in 1 (4.5%), choledochal cyst in 7 (31.8%) and atretic gall bladder suggestive of acquired biliary atresia in one (4.5%) patient. HIDA scan was diagnostic in all 17 (77.27%) in which it was performed. MRCP was done in 3 (13.6%) patients. Mortality frequency was 3/22 (13.6%); one died of post-surgical sepsis second one was cirrhotic at time of presentation and didn't make It. Two were lost to follow up one which died at home while we lost contact with fourth patient. CONCLUSIONS: Spontaneous perforation of bile duct can present and should be suspected as an important cause of neonatal biliary ascites or peritonitis. Most patients can be managed with intravenous antibiotics, percutaneous drainage and ttube insertion while patients with choledochal cysts required cholecystectomy with roux en y choledochjejunostomy. Timely recognition and intervention is associated with favourable outcome.

Frequency, causes and outcome of neonates with respiratory distress admitted to Neonatal Intensive Care Unit, National Institute of Child Health, Karachi.

OBJECTIVE: To determine the frequency, aetiology and outcome of respiratory distress in neonates in intensive care unit. METHODS: The descriptive cross-sectional study was conducted at the Neonatal Intensive Care Unit, National Institute of Child Health, Karachi, from October 2009 to March 2010. It comprised neonates aged day 0 to 28 who were admitted to Neonatal Intensive Care Unit. The neonates were screened first for respiratory distress and presence of one or more signs and symptoms. History, examination and investigations were carried out to find out various aetiologies of respiratory distress. Outcome was measured in terms of discharge and death. Data was analysed using SPSS12. RESULTS: Of the 205 neonates in the study, 120(58.6%) were boys and 85(41.4%) were girls The overall mean age was 70.58±110.02 hours and the mean gestational age was 36.32±2.72 weeks while the mean weight was 2.41±2.4kg. Respiratory rate >60/min was found in all (100%) the neonates. In terms of signs and symptoms, 125(60.9%) had grunting, 205(100%) had subcostal retractions and nasal flaring, and 81(40%) had cyanosis. The aetiologies observed were birth asphyxia, sepsis, transient tachypnoea of the newborn, pneumonia, meconium aspiration syndrome and respiratory distress syndrome in 22(10.75%), 37(18.05%), 29(14.1%), 36(17.6%), 34(16.7%) and 47(23.0%) neonates respectively. The incidence of neonates with respiratory distress was 68(33.3%). CONCLUSIONS: The frequency of respiratory distress among the neonates was high, while mortality was high in neonates with respiratory distress, especially in pre-term and low birthweight neonates. Early diagnosis and management is important for better outcome.

CLINICAL PRESENTATION, AETIOLOGY AND COMPLICATIONS OF PANCREATITIS IN CHILDREN.

BACKGROUND: Childhood Pancreatitis is an uncommon but serious condition with incidence on the rise. It manifests as acute or chronic form with epigastric pain, vomiting and elevated serum -amylase and lipase. This study was conducted with the aim to determine the clinical presentation, aetiology, and complications of pancreatitis in children. METHODS: This descriptive case series was conducted in the Department of Paediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital & the Institute of Child Health, Lahore from 1st January to 31st December 2014. Seventy-two patients up to the age of 15 years having abdominal pain, Amylase >200 IU/L and/or lipase >165 IU/L, with features of acute or chronic pancreatitis on abdominal imaging; were included in study. Data analysis was done using SPSS-20. RESULTS: Of the total 72 patients, 43 (60%) had acute pancreatitis, males were 25 (58%) and females 18 (42%) and chronic pancreatitis was diagnosed in 29 (40%), males 10 (34%) and females 19 (66%). Common clinical features were abdominal pain (100%), nausea and vomiting (79%). Common aetiologies were idiopathic (40%) while choledochal cyst 8%, hyperlipidaemia 7%, biliary tract stones/sludge 7% and abdominal trauma 6%. Complications were more frequently associated with acute pancreatitis (60%) than with chronic pancreatitis (34%). Common complications were pseudo-pancreatic cyst (36%), ascites (17%) and pleural effusion (4%). CONCLUSION: Abdominal pain, nausea and vomiting were common presenting features of childhood pancreatitis. Common aetiologies were idiopathic hyperlipidemia, biliary tract stones/sludge, choledochal cyst and abdominal trauma. Common complications were Pseudo-pancreatic cyst, ascites and pleural effusion.

Etiological diagnosis of undervirilized male/XY disorder of sex development.

OBJECTIVE: To do clinical, hormonal and chromosomal analysis in undervirilized male / XY disorder of sex development and to make presumptive etiological diagnosis according to the new Disorder of Sex Development (DSD) classification system. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Endocrine Unit at National Institute of Child Health, Karachi, Pakistan, from January 2007 to December 2012. METHODOLOGY: Patients of suspected XY DSD / undervirilized male visiting endocrine clinic were enrolled in the study. Criteria suggested XY DSD include overt genital ambiguity, apparent female/male genitalia with inguinal/labial mass, apparent male genitalia with unilateral or bilateral non-palpable testes, micropenis and isolated hypospadias or with undescended testis. The older children who had delayed puberty were also evaluated with respect to DSD. As a part of evaluation of XY DSD, abdominopelvic ultrasound, karyotype, hormone measurement (testosterone, FSH, LH), FISH analysis with SRY probing, genitogram, laparoscopy, gonadal biopsy and HCG stimulation test were performed. Frequencies and percentages applied on categorical data whereas mean, median, standard deviation were calculated for continuous data. RESULTS: A total of 187 patients met the criteria of XY DSD. Age ranged from 1 month to 15 years, 55 (29.4%) presented in infancy, 104 (55.6%) between 1 and 10 years and 28 (15%) older than 10 years. Twenty five (13.4%) were raised as female and 162 as (86.6%) male. The main complaints were ambiguous genitalia, unilateral cryptorchidism, bilateral cryptorchidism, micropenis, delayed puberty, hypospadias, female like genitalia with gonads, inguinal mass. The karyotype was 46 XY in 183 (97.9%), 46 XX in 2 (1.1%), 47 XXY in 1 (0.5%), 45 X/46 XY in 1 (0.5%) patient. HCG stimulation test showed low testosterone response in 43 (23 %), high testosterone response in 62 (33.2%), partial testosterone response in 32 (17.1%) and normal testosterone response in 50 (26.7%). Genitogram was carried out in 86 (45.98%) patients. Presumptive etiological diagnosis of androgen sensitivity syndrome/ 5-alpha reductase deficiency, testicular biosynthetic defect/ leydig cell hypoplasia, partial gonadal dysgenesis, ovotesticular DSD, XX testicular DSD, mixed gonadal dysgenesis, testicular vanishing syndrome, klinefelter syndrome, hypogonadotropic hypogonadism, isolated hypospadias and isolated micropenis was made. CONCLUSION: Clinical, chromosomal and hormonal assessment may help in making the presumptive etiological diagnosis. Further molecular genetics analysis are needed in differentiating these abnormalities and to make a final diagnosis.