PhD in Clinical Sciences
Student Profiles
Mirza Noor Ali Baig
Supervisory Team: Prof. Zafar Fatmi, Primary Supervisor; Prof. Junaid Razzak, Co-Supervisor; Dr Nadeemullah Khan, Committee Member; Dr Uzma Khan, Committee Member
Summary of PhD Project: Sudden cardiac arrest (SCA) is a leading global cause of death, primarily due to cardiac etiologies, though trauma also contributes significantly. Without timely intervention, SCA can rapidly lead to death. Many SCAs occur outside hospitals, known as out-of-hospital cardiac arrests (OHCA), which have high mortality rates despite interventions. In developed countries, OHCA survival rates range from less than 1% to over 25%, influenced by several system-related factors and predictors. Key survival factors include witnessed cardiac arrest, bystander cardiopulmonary resuscitation (CPR), early defibrillation, and return of spontaneous circulation (ROSC). Variations in these predictors arise from disparities in practices and systems managing OHCA patients. Survival largely depends on the "Chain of Survival" (COS), which includes high-quality pre-hospital and in-hospital care.
Developed countries, like the United States, exhibit better OHCA survival rates due to robust COS. In resource-limited settings, OHCA survival rates are often unknown and very low. A multicentre study in Karachi, Pakistan, reported 0% survival (two months post-cardiac arrest) for OHCA, likely due to a non-existent COS and contextually driven health system factors. Most populations in developing countries reside in rural areas, where COS and referral systems are weak or non-existent. Identifying gaps and contextually relevant COS factors in these low-income rural settings is crucial.
This study aims to conduct a mixed-methods investigation to identify gaps in COS and OHCA management in rural Sindh, Pakistan, and determine factors associated with an ineffective COS. Data collection is complete, and data analysis is in progress. The study includes:
- A scoping literature review to understand COS effectiveness for OHCA patients in low-income settings.
- An assessment of management strategies and COS for OHCA in three rural Sindh districts (Thatta, Shaheed Benazirabad, and Shikarpur) using mixed methods, including focus group discussions with community members and ambulance drivers, interviews with emergency healthcare providers and experts, exit interviews of emergency room patients, and health facility record reviews.
Research Publication(s) from PhD Work:
Pakistan's Emergency Medical Services (EMS) system & out-of-hospital-cardiac-arrest (OHCA): A narrative review of an EMS system of a low middle income country in context of OHCA
Farhala Juman
Supervisory Team: Dr Tashfeen Ahmad, Primary Supervisor; Dr Babar Hassan, Co-Supervisor; Dr Laila Ladak, Committee Member; Mr Iqbal Azam, Committee Member; Dr Shazia Mohsin, Committee Member
Summary of PhD Project: Feasibility of implementing CHD ICHOM standard sets aims to evaluate the feasibility of adopting robust evidence based standard set of health outcome measures in routine clinical practice. This mix method implementation study will provide evidence to assess the practicality, demand, and integration of these outcome measures in improving the quality-of-care of congenital heart diseases patients. Our research seeks to advance the shift from volume-based to value-based healthcare particularly in LMICs
Shahan Waheed
Supervisory Team: Prof. Asad Mian, Primary Supervisor; Dr Nadeemullah Khan, Co-Supervisor; Prof. Junaid Razzak, Committee Member
Summary of PhD Project: There are numerous challenges and risks associated with airway management in a critically ill adult. These risks if not timely addressed, result in poor outcomes. Therefore, to secure a definitive airway, emergency physicians must consider both anatomical and physiological factors which tend to dominate in critically ill patients requiring endotracheal intubation. Physiologically difficult airway is defined as an airway that is physiologically challenging and increases the risk of cardiovascular collapse during intubation or conversion to positive pressure ventilation. In emergency airway management, there are several airway assessment scores that focus on anatomical factors of difficulty, but few targets physiological derangements. The objective of this study is to derive and validate a difficult airway physiological score that can predict serious outcomes among critically ill adults using pre-intubation clinical and laboratory parameters. This is an observational single center study with two sequential phases. Phase 1, to identified the frequency of physiologically difficult airways and derived the Difficult Airway Physiological Score (DAPS). Phase 2, to prospectively validate the score among critically ill adults undergoing endotracheal intubation in the emergency department.
Research Publication(s) from PhD Work:
Derivation of the Difficult Airway Physiological Score (DAPS) in adults undergoing endotracheal intubation in the emergency department
Validation of Difficult Airway Physiological Score (DAPS) in Critically Ill Adults Undergoing Endotracheal Intubation in the Emergency Department
A Prospective Study Evaluating Gender Differences of Serious Outcomes through Difficult Airway Physiological Score (DAPS) in the Emergency Department
Altaf Ali Laghari
Supervisory Team: Prof. Ather Enam, Primary Supervisor; Dr Nouman Mughal Co-Supervisor; Dr Hani Abidi, Committee Member; Dr Jing Song Wu, Committee Member
Summary of PhD Project: Glioblastoma (GBM) is the most common and lethal malignancy of the brain. It accounts for 45.2% of all brain tumors and is classified as grade IV glioma by the World Health Organization (WHO). This malignancy results from genetic aberrations and deregulation of signaling pathways. Despite current treatment strategies involving surgery, chemotherapy, and radiotherapy, there is a poor patient survival rate of 15 months.
GBM is driven and maintained by a subpopulation of clonogenic stem cells called Glioma Initiating Cells (GICs), which play a crucial role in its biological behavior. GICs display the malignant phenotype, self-renewal ability, altered genomic stability, and specific epigenetic signature. They can be identified by cell-surface markers, LGR5, L1CAM, CD44, and CD133. These cells lead to resistance to chemo and radiotherapy in glioblastoma patients through the activation of DNA damaged checkpoint responses and the increase in DNA repair capacity. GICs are not distributed homogenously throughout the tumor and only constitute a small portion of tumor cells. A recent study done at AKUH has shown that GICs concentration may vary in accordance with different parts of tumor as per differences identified by MRI. Since tumor growth depends on GICs and understanding of its molecular biology would give us a better knowledge of GBM progression and pathogenesis.
There are several key epigenetics modifications (DNA methylation, histone modification and non-coding RNA) involved in GBM progression, out of these, microRNA have been proven to play an important role. Recent studies have found microRNA are involved in the regulation of proliferation and self-renewal of the GICs where they promote differentiation to determine the fate of stem cell. Further research in a wide range of species as well as multiple cancers heavily indicates the use of microRNAs as biomarkers and possible therapeutic targets. Studies have shown that microRNAs are expressed in a heterogeneous manner throughout the tumor. But these studies investigated the expression of microRNA in tumor tissues. Tumor tissue can have 0.02% to 25% of cancer-initiating stem cells depending on the tumor type, where higher cancer-initiating stem cells proportions are found in undifferentiated tumors. Due to the higher percentage of differentiated cells in glioblastoma biopsy specimen, we plan to identify microRNA(s) contributing to the tumor driving capability of GICs in patient-derived culture after enrichment of GICs population.
A better understanding of the microRNA signature of the GICs in the tumor and their association with their proliferative and invasive potential is crucial to understand GBM pathogenesis.
