Raised Serum Uric Acid as a Predictor of Perinatal Outcome in Parturient with Pregnancy Induced Hypertension

Objective: To evaluate the association of increased uric acid in pregnancy-induced hypertension with adverse perinatal outcomes. Study Design: Comparative cross-sectional study. Place and Duration of Study: Departments of Anesthesia, Gynecology & Obstetrics, Combined Military Hospital, Okara Pakistan, from Mar to Sep 2018. Methodology: After approval of the Hospital Ethical Committee, 106 patients with pregnancy-induced hypertension were included in our study (n=53 in each group). Group-A had patient with raised uric acid, whereas Group-B had normal uric acid. Perinatal outcomes were monitored prospectively. Results: There was no difference in demographic profile of the two study groups. Raised uric acid was shown to be associated with a higher cesarean mode of delivery (p=0.014); preterm delivery (0.001); intrauterine growth retardation (0.038); and low APGAR at 5mintues (0.008). Raised uric had a sensitivity greater than 65% and specificity greater than 50% for perinatal outcomes. Conclusion: Raised uric acid is associated with adverse perinatal outcomes in neonates

A cytogenic monitoring approach of hospital workers occuptionally exposed to ionizing radiations using micronucleus assay

Background: The objective of this study was to determine chromosomal damage in occupational workers of the radiation department from three different hospitals, Faisalabad, Pakistan exposed for a long term to ionizing radiations using micronucles (MN) assay. A comparison between exposed and non-exposed subjects (controlled) of same age exhibited a significant an increase in the number of micronuclei in occupational workers. MN frequency increases with an increase in age and duration of exposure in both sexes but higher in females.Materials and Methods: The study was conducted at the District Head Quarter Hospital (DHQ), Punjab Institute of Nuclear Medicine (PINUM) and Allied Hospital, Faisalabad, Pakistan. The total 145 subjects were selected from these hospitals. The subjects were divided into two groups. The control group (N= 40) (20 males and 20 females) of healthy subjects (no exposure) and the second group of subjects (N=105) (68 males and 37 females) subjects of occupational workers who were indirectly exposed to radiation. Blood samples (2ml) were collected in sodium heparinised vaccutainer tubes through venipuncture from both the groups. Disposable syringes were used for this purpose. For the evaluation of MN yield, slides were prepared by following the method of Jorge et al. (2004).Results: A significant difference in micro nuclear induction was observed between the occupational subjects and the control subjects and as well as in females and in males (P < 0.01). Females are more vulnerable to ionizing radiation than males. In females, MN yield was two times higher than males. MN frequency was increased with an increase in age and duration of exposure in both sexes, but higher in females and may be due to an increase in chromosomal loss in hospital workers. There is an individual response to the physical noxa, depending on sex, age and exposure. Smoking and drinking habits do not have a significant effect in increasing the number of MN in occupationally exposed workers.Conclusion: It was concluded that females are more vulnerable to ionizing radiations than males. MN test can be used as a biomarker with a predictive value for the estimation in occupationally exposed subjects.Key Words: Radiations; Hospital workers; Sex; Micronucleus assay; Chromosomal damag

Health professionals and women's knowledge and experiences of caring for small gestational age (SGA) infants in Pakistan

Background In Pakistan, every third baby is born small for gestational age (SGA). Early antenatal detection of SGA helps with birth planning and initial treatment of mother and baby, thereby reducing complications. Screening and diagnosis of SGA however are challenging, especially in low and middle-income countries where access to technological advances may be limited and there is a lack of routine antenatal screening. Aims To explore the current practices, knowledge, and experiences of caring for SGA infants with women and health professionals in Pakistan. Design A cross-sectional survey with healthcare professionals and focus groups or interviews with health professionals and mothers of SGA babies were undertaken. Survey data were analysed descriptively and integrated with the qualitative data using thematic data analysis. Subjects 78 completed surveys were returned and eight FGDs and five interviews were undertaken with 77 participants – 67 healthcare professionals (gynecologists/obstetricians, neonatologists, Lady Health Workers, and Lady Health Visitors) and 10 mothers of SGA infants aged under 12 months. Results The survey highlighted a general lack of training on SGA for all health care professionals, but particularly amongst community staff who often act as primary caregivers for women. Five qualitative themes described the challenges and issues faced in the management, treatment, and prevention of SGA in Pakistan: Lack of policies and training, Lack of resources, Lack of access to healthcare, Not following the guidance, and Lack of data and reporting. Conclusions A whole system approach to improve service provision and outcomes is needed. This should include epidemiological research, country-specific policies, training for healthcare professionals and awareness raising amongst women and community members

A CYTOGENIC MONITORING APPROACH OF HOSPITAL WORKERS OCCUPTIONALLY EXPOSED TO IONIZING RADIATIONS USING MICRONUCLEUS ASSAY

Background: The objective of this study was to determine chromosomal damage in occupational workers of the radiation department from three different hospitals, Faisalabad, Pakistan exposed for a long term to ionizing radiations using micronucles (MN) assay. A comparison between exposed and non-exposed subjects (controlled) of same age exhibited a significant an increase in the number of micronuclei in occupational workers. MN frequency increases with an increase in age and duration of exposure in both sexes but higher in females. Materials and Methods: The study was conducted at the District Head Quarter Hospital (DHQ), Punjab Institute of Nuclear Medicine (PINUM) and Allied Hospital, Faisalabad, Pakistan. The total 145 subjects were selected from these hospitals. The subjects were divided into two groups. The control group (N= 40) (20 males and 20 females) of healthy subjects (no exposure) and the second group of subjects (N=105) (68 males and 37 females) subjects of occupational workers who were indirectly exposed to radiation. Blood samples (2ml) were collected in sodium heparinised vaccutainer tubes through venipuncture from both the groups. Disposable syringes were used for this purpose. For the evaluation of MN yield, slides were prepared by following the method of Jorge et al. (2004). Results: A significant difference in micro nuclear induction was observed between the occupational subjects and the control subjects and as well as in females and in males (P < 0.01). Females are more vulnerable to ionizing radiation than males. In females, MN yield was two times higher than males. MN frequency was increased with an increase in age and duration of exposure in both sexes, but higher in females and may be due to an increase in chromosomal loss in hospital workers. There is an individual response to the physical noxa, depending on sex, age and exposure. Smoking and drinking habits do not have a significant effect in increasing the number of MN in occupationally exposed workers. Conclusion: It was concluded that females are more vulnerable to ionizing radiations than males. MN test can be used as a biomarker with a predictive value for the estimation in occupationally exposed subjects

Biofortification of wheat with zinc for eliminating deficiency in Pakistan: Study protocol for a cluster-randomised, double-blind, controlled effectiveness study (BIZIFED2)

Introduction: Micronutrient deficiencies, commonly referred to as “hidden hunger”, affect more than two billion people worldwide, with zinc and iron deficiency frequently reported. The aim of this study is to examine the impact of consuming zinc biofortified flour (Zincol-2016) on biochemical and functional measures of status in adolescent girls and children living in a low resource setting in Pakistan. Methods and analysis: We are conducting a pragmatic, cluster-randomised, double-blind, controlled trial. A total of 483 households have been recruited from two catchment areas approximately 30-40 km distance from Peshawar. Household inclusion criteria are the presence of both an adolescent girl, aged 10-16 years, and a child aged 2-5 years. The study duration is 12 months, divided into two 6-month phases. During phase 1, all households will be provided with locally procured flour from standard varieties of wheat. During phase 2, clusters will be paired, and randomised to either the control or intervention arm of the study. The intervention arm will be provided with zinc biofortified wheat flour, with a target zinc concentration of 40 mg/kg. The control arm will be provided with locally procured wheat flour from standard varieties with an expected zinc concentration of 20 mg/kg. The primary outcome measure is plasma zinc concentration. Secondary outcomes include anthropometric measurements, biomarkers of iron and zinc status, and the presence and duration of respiratory tract infections and diarrhoea. Ethics and dissemination: Ethical approval was granted from the University of Central Lancashire STEMH Ethics Committee (reference number: STEMH 1014) and Khyber Medical University Ethics Committee (DIR/KMU-EB/BZ/000683). The final study methods will be published in peer reviewed journals, alongside the study outcomes. In addition, findings will be disseminated to the scientific community via conference presentations and abstracts and communicated to the study participants through the village elders at an appropriate community forum. Registration details: The trial has been registered with the ISRCTN registry, study ID ISRCTN17107812

Spatial, temporal, and demographic patterns in prevalence of chewing tobacco use in 204 countries and territories, 1990-2019 : a systematic analysis from the Global Burden of Disease Study 2019

Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Findings In 2019, 273 center dot 9 million (95% uncertainty interval 258 center dot 5 to 290 center dot 9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 center dot 72% (4 center dot 46 to 5 center dot 01). 228 center dot 2 million (213 center dot 6 to 244 center dot 7; 83 center dot 29% [82 center dot 15 to 84 center dot 42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global agestandardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 center dot 21% [-1 center dot 26 to -1 center dot 16]), similar progress was not observed for chewing tobacco (0 center dot 46% [0 center dot 13 to 0 center dot 79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 center dot 94% [-1 center dot 72 to -0 center dot 14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Summary Background Chewing tobacco and other types of smokeless tobacco use have had less attention from the global health community than smoked tobacco use. However, the practice is popular in many parts of the world and has been linked to several adverse health outcomes. Understanding trends in prevalence with age, over time, and by location and sex is important for policy setting and in relation to monitoring and assessing commitment to the WHO Framework Convention on Tobacco Control. Methods We estimated prevalence of chewing tobacco use as part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 using a modelling strategy that used information on multiple types of smokeless tobacco products. We generated a time series of prevalence of chewing tobacco use among individuals aged 15 years and older from 1990 to 2019 in 204 countries and territories, including age-sex specific estimates. We also compared these trends to those of smoked tobacco over the same time period. Findings In 2019, 273 & middot;9 million (95% uncertainty interval 258 & middot;5 to 290 & middot;9) people aged 15 years and older used chewing tobacco, and the global age-standardised prevalence of chewing tobacco use was 4 & middot;72% (4 & middot;46 to 5 & middot;01). 228 & middot;2 million (213 & middot;6 to 244 & middot;7; 83 & middot;29% [82 & middot;15 to 84 & middot;42]) chewing tobacco users lived in the south Asia region. Prevalence among young people aged 15-19 years was over 10% in seven locations in 2019. Although global age standardised prevalence of smoking tobacco use decreased significantly between 1990 and 2019 (annualised rate of change: -1 & middot;21% [-1 & middot;26 to -1 & middot;16]), similar progress was not observed for chewing tobacco (0 & middot;46% [0 & middot;13 to 0 & middot;79]). Among the 12 highest prevalence countries (Bangladesh, Bhutan, Cambodia, India, Madagascar, Marshall Islands, Myanmar, Nepal, Pakistan, Palau, Sri Lanka, and Yemen), only Yemen had a significant decrease in the prevalence of chewing tobacco use, which was among males between 1990 and 2019 (-0 & middot;94% [-1 & middot;72 to -0 & middot;14]), compared with nine of 12 countries that had significant decreases in the prevalence of smoking tobacco. Among females, none of these 12 countries had significant decreases in prevalence of chewing tobacco use, whereas seven of 12 countries had a significant decrease in the prevalence of tobacco smoking use for the period. Interpretation Chewing tobacco remains a substantial public health problem in several regions of the world, and predominantly in south Asia. We found little change in the prevalence of chewing tobacco use between 1990 and 2019, and that control efforts have had much larger effects on the prevalence of smoking tobacco use than on chewing tobacco use in some countries. Mitigating the health effects of chewing tobacco requires stronger regulations and policies that specifically target use of chewing tobacco, especially in countries with high prevalence. Copyright (c) 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990-2019 : a systematic analysis from the Global Burden of Disease Study 2019

Background Ending the global tobacco epidemic is a defining challenge in global health. Timely and comprehensive estimates of the prevalence of smoking tobacco use and attributable disease burden are needed to guide tobacco control efforts nationally and globally. Methods We estimated the prevalence of smoking tobacco use and attributable disease burden for 204 countries and territories, by age and sex, from 1990 to 2019 as part of the Global Burden of Diseases, Injuries, and Risk Factors Study. We modelled multiple smoking-related indicators from 3625 nationally representative surveys. We completed systematic reviews and did Bayesian meta-regressions for 36 causally linked health outcomes to estimate non-linear dose-response risk curves for current and former smokers. We used a direct estimation approach to estimate attributable burden, providing more comprehensive estimates of the health effects of smoking than previously available. Findings Globally in 2019, 1.14 billion (95% uncertainty interval 1.13-1.16) individuals were current smokers, who consumed 7.41 trillion (7.11-7.74) cigarette-equivalents of tobacco in 2019. Although prevalence of smoking had decreased significantly since 1990 among both males (27.5% [26. 5-28.5] reduction) and females (37.7% [35.4-39.9] reduction) aged 15 years and older, population growth has led to a significant increase in the total number of smokers from 0.99 billion (0.98-1.00) in 1990. Globally in 2019, smoking tobacco use accounted for 7.69 million (7.16-8.20) deaths and 200 million (185-214) disability-adjusted life-years, and was the leading risk factor for death among males (20.2% [19.3-21.1] of male deaths). 6.68 million [86.9%] of 7.69 million deaths attributable to smoking tobacco use were among current smokers. Interpretation In the absence of intervention, the annual toll of 7.69 million deaths and 200 million disability-adjusted life-years attributable to smoking will increase over the coming decades. Substantial progress in reducing the prevalence of smoking tobacco use has been observed in countries from all regions and at all stages of development, but a large implementation gap remains for tobacco control. Countries have a dear and urgent opportunity to pass strong, evidence-based policies to accelerate reductions in the prevalence of smoking and reap massive health benefits for their citizens. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Plasma proteomics for detection of early stage colorectal cancer biosignatures

Thesis by publication.Bibliography: pages 252-267.Chapter 1. Introduction -- Chapter 2. General materials and methods -- Chapter 3. Isolation of comprehensive human plasma peptidomes -- Chapter 4. An assessment of anticoagulants in blood collection tubes on the stability of comprehensive proteomic analysis -- Chapter 5. A novel multiplexed immunoassay identifies CEA, IL-8 and prolactin as prospective markers for Dukes' stages A-D colorectal cancers -- Chapter 6. A SWAT MS based proteomic investigation for detection of early stage CRC biosignatures.Colorectal cancer (CRC) is one of the top three most common cancers worldwide. In Australia, CRC alone accounted for around 13% of all new cancer cases and 10% of all cancer deaths. Early CRC detection is critical for improved survival rates and more effective treatment. Blood is an easily accessible circulating fluid that reflects the current physiological and health state of an individual. For this reason, it is thought to be one of the best sources of protein or peptide biomarkers that reflect the health or clinical status of an individual.This PhD initially addresses the possible challenges for developing a robust reproducible Tri-Tricine SDS PAGE-based technique for capturing and identifying the endogenous intact LMW protein/peptide plasma "peptidome". It compares this attempt with other conventional methods (i.e., extraction using membrane filtration with 30 KDa cut off, differential solubilization and SPE C18 chromatography) that have been practiced for the isolation of intact LMW propteins/peptides from complex biospecimens. Following that, the thesis examines the suitability of spray-dried EDTA-treated plasma samples for proteomic biomarker discovery investigations against recently developed proprietary tubes containing a cocktail of protease inhibitors (PIs).A range of proteomic analyses have been conducted on CRC plasma samples (age, sex matched with stringent exclusion/inclusion criteria) obtained from the Victoria Biobank. These investigations included immune-based multiplex assays using two different approaches: Proseek® Multiplex Oncology kit I (Proseek assay) based on novel Proximity Extension Assay (PEA) technology with real time PCR (Olink Biosciences) and Bio-Plex Pro™ human cytokine27-plex kit. The high throughput multiplex assay has identified three potential candidate biomarkers (CEA, IL-8 and prolactin) that were expressed among Dukes’ stages as well as healthy, benign and malignant groups. Finally, an extensive investigation to explore the available techniques for deep depletion of the complex plasma proteome is conducted, in the hope of allowing identification of lower abundance clinical stage specific novel diagnostic plasma biomarkers for CRC. A follow up study was designed to immunodeplete pooled CRC plasmas using commercially available Agilent MARS 14 as well as our in house patented immune based depletion methods. The depleted samples were analyzed through a data independent acquisition (DIA) method (SWATH-MS), and demonstrated that cystatin C,paraoxonase-1 and ADAM DEC1 were potential candidate biomarkers for stage specific CRC (i.e., significantly overexpressed in CRC patients). The findings reported in this thesis hold great promise for future identification of low abundance plasma proteomic biomarkers for CRC.Mode of access: World wide web1 online resource (xx, 423 pages) illustrations (some colour