Assessment of Dengue Fever Severity Through Liver Function Test

Objective: To assess the utility of liver function tests (LFTs) for early recognition and prediction of severity of dengue fever in hospitalized patients. Study Design: An analytical study. Place and duration of study: Services Institute of Medical Science and Fatima Memorial Hospital, Lahore, from September to December 2010. Methodology: Admitted cases of dengue fever were divided into three groups: mild, moderate, and severe increases in aminotransferases. Elevation in LFTs was co-related with good or bad outcome i.e. (survival or complication free stay) or (death or complications). Results were analyzed in SPSS version 18. Results: Out of the 353 patients with mean age of 37.12 ± 15.45 years, 245 (69.4%) were males and 108 (30.6%) were females. Seventy five patients (21.2%) had mild elevation of aminotransferases (twofold increases), 265 patients (75.1%) had moderate increases (three to fourfold), and 13 (3.7%) had severe (>4 fold increase). Alanine transaminase (ALT) was statistically higher in patients with septicemia, hepatic, and renal failure (p-value ≤0.05). Aspartate transaminase (AST) was higher in almost all complications. Prolonged hospital stay was associated with raised LFTs and greater complications and mortality. AST was found to be twice as much raised as ALT. Conclusion: AST and ALT were statistically higher in patients with worse outcome thus can lead to early recognition of high risk cases

Gastroesophageal Reflux Disease in Patients with Chronic Obstructive Pulmonary Disease

Objective: To determine the frequency of gastroesophageal reflux disease (GERD) in patients with chronic obstructive pulmonary disease in our population Methodology: This cross-sectional study was conducted at medical out-patient Department, Services Hospital, Lahore; from September 2014 to March 2015. All the patients having chronic obstructive pulmonary disorder (COPD) were included. COPD was defined as the patients having a ratio of “forced expiratory volume in one second” (FEVI) to “forced vital capacity” (FVC) below 70% and having no improvement in FEVI after bronchodilator. Severity GERD was categorized as per episodes of symptoms. Information regarding the frequency of GERD was collected via study proforma. Data was analyzed using SPSS version 16.  Results:  Overall 100 cases were studied; their mean age was 47.54+3.62 years. Out of all 90% were males and 10% were females. Frequency of GERD in patients with COPD reveals 33%, followed by 03% study subjects had mild GERD, 7% had moderate, 11% had severe and 12% had very severe symptoms of GERD, while 67% had no nay symptoms of GERD. Conclusion: In the conclusion the frequency of gastroesophageal reflux disease (GERD) was found to be 33.0% among COPD subjects.

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

MTRR gene variants may predispose to the risk of Congenital Heart Disease in Down syndrome patients of Indian origin

Background: Down syndrome (DS), also called as trisomy 21, is one of the most leading cause of intellectual disability. DS is associated with a number of phenotypes including Congenital Heart Disease (CHD), Leukemia, Alzheimer’s disease, Hirschsprung’s disease and others. DS affects about 1 in 700 live births. Objectives: The study aims to investigate the association of MTRR (Methionine synthase reductase) gene polymorphisms (C524T and A66G) with the risk of CHD in DS patients. Methods: PCR and PCR-RFLP methods were used for the genotyping of study samples and results were validated using Sanger’s sequencing. Results: MTRR C524T and A66G were significantly associated with the increased risk of CHD in DS. We have also reported two novel polymorphisms, T19775C and 19778_19778delG, in DS with CHD cases with a frequency of 93% and 40%, respectively. These two polymorphisms were not found among DS without CHD group. Conclusion: Results from this study indicate that the MTRR C524T and A66G polymorphisms influence the risk of the occurrence of CHD in DS patients of Indian Origin. This is the first report from India highlighting the potential association of MTRR C524T and A66G polymorphisms with CHD in DS. We are also the first one to report two novel polymorphisms, T19775C and 19778_19778delG in DS with CHD group. Hence these four polymorphisms can be used to evaluate the risk of CHD in DS patients

Maternal Risk Factors Triggering Congenital Heart Defects in Down Syndrome: A Case-Control Study

Objectives: Maternal MTHFR and MTRR polymorphisms as a risk of CHD in DS fetus were studied along with maternal folic acid supplementation, which could influence the folate metabolism along with other risk factors. Material and Methods: A case-control study comprising of mothers of DS with and without CHD along with controls were recruited from a tertiary care center since 2018–2019. Genomic DNA was isolated followed by PCR-RFLP. Results: Mothers with age ≥35 years and having history of miscarriages have a higher risk of giving birth to DS with CHD (n = 35% and 42%, respectively). Mothers who carried the MTHFR 677CT/TT and MTRR 524CT/TT genotypes combination in the folic acid nonusers group during pregnancies had six-fold (OR = 6.909, p-value = 0.027; 95% CI—1.23 ± 38.51) and four-fold (OR = 4.75, p-value = 0.040; 95% CI—1.067 ± 21.44) increased odds of having a DS child with CHD, respectively, as compared to folic acid users. Conclusion: Maternal age, folic acid supplementation, and previous history of miscarriages is involved in the etiology of CHD in DS fetus in Indian population. Maternal MTHFR and MTRR polymorphisms are also involved in the occurrence of CHD and DS in Indian population when controlling for periconceptional folic acid supplementation. Limitations: Single-Centered Stud

Identification of Novel Genomic Variations in Susceptibility to Nonsyndromic Cleft Lip and Palate Patients

Background: Nonsyndromic cleft lip with or without palate (NSCL/P) is a multifactorial and common birth malformation caused by genetic and environmental factors, as well as by teratogens. Genome-wide association studies found genetic variations with modulatory effects of NSCL/P formation in Chinese and Iranian populations. We aimed to identify the susceptibility of single-nucleotide polymorphisms (SNPs) to nonsyndromic cleft lip with or without palate in the Indian population. Material and Methods: The present study was conducted on NSCL/P cases and controls. Genomic DNA was extracted from peripheral blood and Axiom- Precision Medicine Research Array (PMRA) was performed. The Axiom-PMRA covers 902,527 markers and several thousand novel risk variants. Quality control-passed samples were included for candidate genetic variation identification, gene functional enrichment, and pathway and network analysis. Results: The genome-wide association study identified fourteen novel candidate gene SNPs that showed the most significant association with the risk of NSCL/P, and eight were predicted to have regulatory sequences. Conclusion: The GWAS study showed novel candidate genetic variations in NSCL/P formations. These findings contribute to the understanding of genetic predisposition to nonsyndromic cleft lip with or without palate

Association between maternal experiences of intimate partner violence and child stunting: a secondary analysis of the Demographic Health Surveys of four South Asian countries

Objectives To determine the association between maternal exposure to intimate partner violence (IPV) and child stunting using the Demographic Health Survey (DHS) data comparing four South Asian countries.Design A secondary analysis.Setting Data from the seventh round of the DHS data of four South Asian countries; Pakistan, Nepal, India and Maldives.Participants Married women of reproductive age (15–49 years) from each household were randomly selected, having at least one child less than 5 years of age for whom all anthropometric measures were available.Outcome measure The exposure variable was maternal IPV including, sexual violence, physical violence or both. The outcome variable was moderate or severe stunting, measured based on the height-for-age Z-score of children aged 6–59 months old . Multiple Cox proportional regression analyses were used separately on each country’s data to determine the association between maternal IPV and child stunting.Results The prevalence of IPV among women ranged from 10.17% in the Maldives to 31% in India. The burden of child stunting was the lowest in the Maldives at 14.04% and the highest in Pakistan at 35.86%. The number of severely stunted children was the highest in Pakistan (16.60%), followed by India (14.79%). In India, children whose mothers were exposed to IPV showed a 7% increase in the prevalence of moderate to severe child stunting (OR 1.07; 95% CI 1.01 to 1.14). Additionally, in Nepal, severe stunting was strongly associated with the prevalence of physical IPV (OR 1.66; 95% CI 1.01 to 2.87).Conclusion Our study findings suggest that maternal exposure to IPV is associated with child stunting. Further research investigating the relationship between IPV and child outcomes using improved and advanced statistical analyses can provide substantial evidence to enhance public awareness and potentially reduce the burden of child stunting in South Asian countries

HepFREEPak: protocol for a multi-centre, prospective observational study examining efficacy and impact of current therapies for the treatment of hepatitis C in Pakistan and reporting resistance to antiviral drugs: study protocol

Background: Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization\u27s goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan.Methods: This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection.Conclusion: The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan