Extent of liver inflammation in predicting response to interferon alpha & Ribavirin in chronic hepatitis C patients: a cohort study

Background: Liver inflammation due to HCV infection leads to fibrosis, which is an independent predictor of treatment response to interferon therapy in Chronic Hepatitis C (CHC) patients. This relationship has not been studied for liver inflammation on pretreatment liver biopsy and End of Treatment Response (ETR). ALT is a less invasive test than liver biopsy for measuring liver inflammation. Aim of this study was to compare ETR to Interferon alpha (recombinant Interferon) & Ribavirin in CHC patients having higher and lower grades of liver inflammation and to determine the diagnostic accuracy of pretreatment ALT for grades of liver inflammation.Methods: A retrospective cohort of 876 naive CHC patients, who completed Interferon alpha & Ribavirin for 24weeks, was studied for ETR. Pretreatment grade of inflammation on liver biopsy was taken as the exposure variable. It was classified as high if there was moderate or severe and low if there was minimal or mild. Multivariable logistic regression modeling was performed. Diagnostic accuracy of pretreatment ALT for liver inflammation grades was determined by computing Area Under the Receiver Operator Curve (AUROC).Results: Of all patients, 672 having diagnostic liver biopsy and ETR available were analyzed. Among them, 103 had high and 569 had low grades of liver inflammation. Mean age was 36.9 (SD 9.1) years, with patients with high grades being older than those with low grades inflammation (p=0.03). High grades of liver inflammation was associated with ETR (RR 1.17, 95% CI 1.12-1.18) adjusting for age, Total Leukocyte count (TLC) and pretreatment levels of ALT, irrespective of liver fibrosis. This relation remained significant for \u27bridging fibrosis and cirrhosis\u27 and not for \u27no\u27 or \u27portal fibrosis\u27. AUROC of pretreatment ALT for males and females was moderately accurate for severe inflammation compared to minimal inflammation and less accurate for high grades compared to low grades.CONCLUSIONS: ETR in patients with higher grades of liver inflammation was 17% higher than those with lower grades irrespective of fibrosis and 9% higher for bridging fibrosis and cirrhosis. Pretreatment ALT was moderately accurate for severe inflammation only on liver biopsy in both males and females

Development and validation of sunlight exposure measurement questionnaire (SEM-Q) for use in adult population residing in Pakistan

Background: Vitamin D deficiency has been identified as a major public health problem worldwide. Sunlight is the main source of vitamin D and its measurement using dosimeters is expensive and difficult for use in population-based studies. Hence, the aim of this study was to develop and validate questionnaires to assess sunlight exposure in healthy individuals residing in Karachi, Pakistan. Methods: Two questionnaires with seven important items for sunlight exposure assessment were developed. Fifty four healthy adults were enrolled based on their reported sunlight exposure (high = 17, moderate = 18, low = 19) from Aga Khan University, Karachi. Over four days, study participants were asked to wear a dosimeter between sunrise and sunset and report time spent and activities undertaken in the sun for questionnaire validation. Algorithm for item weightage was created as an average score based on ultraviolet B percentage received. Blood samples were obtained for serum vitamin D. Results: The mean time (minutes) spent in sun over 4 days (±SD) was 69.5 (±32) for low, 83.5 (±29.7) for moderate and 329 (±115) for high exposure group. The correlation between average time (minutes) spent in sun over 4 days and mean change in absorbance of UV dosimeters for 4 days was 0.60 (p \u3c 0.01). Correlation between average score and vitamin D levels was found to be 0.36 (p = 0.01) for short term questionnaire score, 0.43 (p = 0.01) for long term questionnaire score in summers and 0.48 (p = 0.01) in winters. Conclusions: The sunlight exposure measurement questionnaires were valid tools for use in large epidemiological studies to quantify sunlight exposure

Childhood and adolescent obesity: Primary Health Care Physicians’ perspectives from Riyadh, Saudi Arabia

BACKGROUND & OBJECTIVES: Primary health care (PHC) physicians are foremost to confront childhood and adolescent obesity. Our objective was to evaluate PHC Physicians perspectives for managing overweight/obesity in children and adolescents. METHODS: PHC services from eight public hospitals in Riyadh participated. A self-administered tool maintaining anonymity evaluated facilitators and barriers for managing overweight/obese children and adolescent patients. Physicians who \u27always\u27 recommended weight management for an overweight / obese patient during past year, by involving patient, parents, and others were classified as having positive and appropriate practice. RESULTS: Of the 58 respondents, 51.7% had appropriate practices. Lack of patient motivation (82.2%), and parental involvement (70.7%) were the major barriers. Physicians with appropriate practices differed in perspectives from those with less appropriate practices by attending continued education forums (p\u3c0.026), referring patients to sub-specialty (p\u3c 0.041), clinical knowledge (p\u3c0.039), convinced on interventions (p\u3c0.017), low concern for precipitating eating disorders (p\u3c0.019), comfortable in examining obese patients (p\u3c0.020), and considered patient\u27s readiness for weight change (p\u3c 0.007). CONCLUSION: Efforts are needed to equip PHC physicians in managing overweight and obesity in Saudi children and adolescents

Phylogenetic and drug-resistance analysis of HIV-1 sequences from an extensive paediatric HIV-1 outbreak in Larkana, Pakistan

Introduction: In April 2019, an HIV-1 outbreak among children occurred in Larkana, Pakistan, affecting more than a thousand children. It was assumed that the outbreak originated from a single source, namely a doctor at a private health facility. In this study, we performed subtype distribution, phylogenetic and drug-resistance analysis of HIV-1 sequences from 2019 outbreak in Larkana, Pakistan.Methods: A total of 401 blood samples were collected between April-June 2019, from children infected with HIV-1 aged 0-15 years recruited into a case-control study to investigate the risk factors for HIV-1 transmission. Partial HIV-1 pol sequences were generated from 344 blood plasma samples to determine HIV-1 subtype and drug resistance mutations (DRM). Maximum-likelihood phylogenetics based on outbreak and reference sequences was used to identify transmission clusters and assess the relationship between outbreak and key population sequences between and within the determined clusters. Bayesian analysis was employed to identify the time to the most recent common recent ancestor (tMRCA) of the main Pakistani clusters.Results: The HIV-1 circulating recombinant form (CRF) 02_AG and subtype A1 were most common among the outbreak sequences. Of the treatment-naïve participants, the two most common mutations were RT: E138A (8%) and RT: K219Q (8%). Four supported clusters within the outbreak were identified, and the median tMRCAs of the Larkana outbreak sequences were estimated to 2016 for both the CRF02_AG and the subtype A1 clusters. Furthermore, outbreak sequences exhibited no phylogenetic mixing with sequences from other high-risk groups of Pakistan.Conclusion: The presence of multiple clusters indicated a multi-source outbreak, rather than a single source outbreak from a single health practitioner as previously suggested. The multiple introductions were likely a consequence of ongoing transmission within the high-risk groups of Larkana, and it is possible that the so-called Larkana strain was introduced into the general population through poor infection prevention control practices in healthcare settings. The study highlights the need to scale up HIV-1 prevention programmes among key population groups and improving infection prevention control in Pakistan

The impact of disease control measures on the spread of COVID-19 in the province of Sindh, Pakistan

The province of Sindh reported the first COVID-19 case in Pakistan on 26(th) February 2020. The Government of Sindh has employed numerous control measures to limit its spread. However, for low-and middle-income countries such as Pakistan, the management protocols for controlling a pandemic are not always as definitive as they would be in other developed nations. Given the dire socio-economic conditions of Sindh, continuation of province-wise lockdowns may inadvertently cause a potential economic breakdown. By using a data driven SEIR modelling framework, this paper describes the evolution of the epidemic projections because of government control measures. The data from reported COVID-19 prevalence and google mobility is used to parameterize the model at different time points. These time points correspond to the government’s call for advice on the prerequisite actions required to curtail the spread of COVID-19 in Sindh. Our model predicted the epidemic peak to occur by 18(th) June 2020 with approximately 3500 reported cases at that peak, this projection correlated with the actual recorded peak during the first wave of the disease in Sindh. The impact of the governmental control actions and religious ceremonies on the epidemic profile during this first wave of COVID-19 are clearly reflected in the model outcomes through variations in the epidemic peaks. We also report these variations by displaying the trajectory of the epidemics had the control measures been guided differently; the epidemic peak may have occurred as early as the end of May 2020 with approximately 5000 reported cases per day had there been no control measures and as late as August 2020 with only around 2000 cases at the peak had the lockdown continued, nearly flattening the epidemic curve

Root-Cause Analysis of Persistently High Maternal Mortality in a Rural District of Indonesia: Role of Clinical Care Quality and Health Services Organizational Factors

Background: Despite significant reduction in maternal mortality, there are still many regions in the world that suffer from high mortality. District Kutai Kartanegara, Indonesia, is one such region where consistently high maternal mortality was observed despite high rate of delivery by skilled birth attendants.Method: Thirty maternal deaths were reviewed using verbal autopsy interviews, terminal event reporting, medical records\u27 review, and Death Audit Committee reports, using a comprehensive root-cause analysis framework including Risk Identification, Signal Services, Emergency Obstetrics Care Evaluation, Quality, and 3 Delays.Findings: The root causes were found in poor quality of care, which caused hospital to be unprepared to manage deteriorating patients. In hospital, poor implementation of standard operating procedures was rooted in inadequate skills, lack of forward planning, ineffective communication, and unavailability of essential services. In primary care, root causes included inadequate risk management, referrals to facilities where needed services are not available, and lack of coordination between primary healthcare and hospitals.Conclusion: There is an urgent need for a shift in focus to quality of care through knowledge, skills, and support for consistent application of protocols, making essential services available, effective risk assessment and management, and facilitating timely referrals to facilities that are adequately equipped

Does malaria during pregnancy affect the newborn?

Objective: To investigate the effect of malarial infection during pregnancy on the newborn.Methods: A retrospective cohort study was conducted at The Aga Khan University Hospital (AKUH), Karachi, using in-patient hospital records over an 11-year period from 1988 to 1999. The incidence of preterm delivery, low birth weight (LBW) and intrauterine growth retardation (IUGR) in 29 pregnant women with malaria, was compared with that in 66 selected pregnant women without malaria, who delivered at the AKUH during the same time period.Results: Pregnant women with malaria had a 3.1 times greater risk of preterm labor (p=0.14). They were more likely to be anaemic compared to women without malaria (RR=2.9, 95% CI=1.6-5.4) and had a significantly lower mean haemoglobin level (p=0.0001). Maternal malaria was significantly associated with LBW babies (p=0.001). The mean birth weight of infants born to pregnant women with malaria was 461 g less (p=0.0005). No significant association was, however, found between malarial infection during pregnancy and IUGR (p=0.33).CONCLUSION: Malarial infection during pregnancy is associated with poor maternal and fetal outcome. It is significantly associated with maternal anaemia and LBW infants. Appropriate measures must, therefore, be taken to prevent malaria during pregnancy, especially in endemic areas

Impact of a multifaceted intervention on physicians' knowledge, attitudes and practices in relation to pharmaceutical incentivisation: protocol for a randomised control trial.

INTRODUCTION: In settings where the private sector constitutes a larger part of the health system, profit-gathering can take primacy over patients' well-being. In their interactions with pharmaceutical companies, private general practitioners (GPs) can experience the conflict of interest (COI), a situation whereby the impartiality of GPs' professional decision making may be influenced by secondary interests such as financial gains from prescribing specific pharmaceutical brands. METHODS AND ANALYSIS: This study is a randomised controlled trial to assess the impact of a multifaceted intervention on GPs' medical practice. The study sample consists of 419 registered GPs who own/work in private clinics and will be randomly assigned to intervention and control groups. The intervention group GPs will be exposed to emotive and educational seminars on medical ethics, whereas control group GPs will be given seminars on general medical topics. The primary outcome measure will be GPs' prescribing practices, whereas the secondary outcome measures will be their knowledge and attitudes regarding COI that arises from pharmaceutical incentivisation. In addition to a novel standardised pharmaceutical representatives (SPSR) method, in which field researchers will simulate pharmaceutical marketing with GPs, presurvey and postsurvey, and qualitative interviewing will be performed to collect data on GPs' knowledge, attitudes and practices in relation to COI linked with pharmaceutical incentives. Univariate and multivariate statistical analyses will be performed to measure a change in GPs' knowledge, attitudes and practices, while qualitative analysis will add to our understanding of the quantitative SPSR data. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Pakistan National Bioethics Committee (# 4-87/NBC-582/21/1364), the Aga Khan University (# 2020-4759-1129) and the London School of Hygiene and Tropical Medicine (# 26506). We will release results within 6-9 months of the study's completion. TRIAL REGISTRATION NUMBER: ISRCTN12294839