A Journey of Innovation: 40 years of Pioneering Medical Education at the Aga Khan University Medical College in Karachi, Pakistan.

This article presents an overview of Aga Khan University's (AKU) pioneering medical education initiatives over the past 40 years, exploring its impact on healthcare in the region and its commitment to advancing medical education and research in the developing world. Established in 1983 as the first private university in Pakistan, AKU has evolved into a global institution with a focus on improving healthcare standards and addressing healthcare needs in the developing world. The article also discusses the undergraduate and postgraduate medical education programs at AKU Medical College, Pakistan, highlighting their unique features and pioneering approaches to medical education. The institution's journey highlights its ability to adapt to the evolving healthcare landscape while maintaining a focus on quality and excellence, offering a model for other institutions striving to meet healthcare needs in low- and middle-income countries.

Early detection of malignant and pre-malignant peripheral nerve tumors using cell-free DNA fragmentomics.

Early detection of neurofibromatosis type 1 (NF1) associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, potentially averting deadly outcomes. Here, we describe a cell-free DNA (cfDNA) fragmentomic approach which distinguishes non-malignant, pre-malignant and malignant forms of NF1 PNST. Using plasma samples from a novel cohort of 101 NF1 patients and 21 healthy controls, we validated that our previous cfDNA copy number alteration (CNA)-based approach identifies malignant peripheral nerve sheath tumor (MPNST) but cannot distinguish among benign and premalignant states. We therefore investigated the ability of fragment-based cfDNA features to differentiate NF1-associated tumors including binned genome-wide fragment length ratios, end motif analysis, and non-negative matrix factorization deconvolution of fragment lengths. Fragmentomic methods were able to differentiate pre-malignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management. Overall, this study pioneers the early detection of malignant and premalignant peripheral nerve sheath tumors in NF1 patients using plasma cfDNA fragmentomics. In addition to screening applications, this novel approach distinguishes atypical neurofibromas from benign plexiform neurofibromas and malignant peripheral nerve sheath tumors, enabling more precise clinical diagnosis and management.

Methodological analysis of a community-based training initiative using the EPIS framework: an ongoing initiative to empower 10 million bystanders in CPR and bleeding control.

Background: Out-of-hospital cardiac arrest (OHCA) and life-threatening bleeding from trauma are leading causes of preventable mortality globally. Early intervention from bystanders can play a pivotal role in increasing the survival rate of victims. While great efforts for bystander training have yielded positive results in high-income countries, the same has not been replicated in low and middle-income countries (LMICs) due to resources constraints. This article describes a replicable implementation model of a nationwide program, aimed at empowering 10 million bystanders with basic knowledge and skills of hands-only cardiopulmonary resuscitation (CPR) and bleeding control in a resource-limited setting. Methods: Using the EPIS (Exploration, Preparation, Implementation and Sustainment) framework, we describe the application of a national bystander training program, named 'Pakistan Life Savers Programme (PLSP)', in an LMIC. We discuss the opportunities and challenges faced during each phase of the program's implementation and identify feasible and sustainable actions to make them reproducible in similar low-resource settings. Results: A high mortality rate owing to OHCA and traumatic life-threatening bleeding was identified as a national issue in Pakistan. After intensive discussions during the exploration phase, PLSP was chosen as a potential solution. The preparation phase oversaw the logistical administration of the program and highlighted avenues using minimal resources to attain maximum outreach. National implementation of bystander training started as a pilot in suburban schools and expanded to other institutions, with 127 833 bystanders trained to date. Sustainability of the program was targeted through its addition in a single national curriculum taught in schools and the development of a cohesive collaborative network with entities sharing similar goals. Conclusion: This article provides a methodological framework of implementing a national intervention based on bystander response. Such programs can increase bystander willingness and confidence in performing CPR and bleeding control, decreasing preventable deaths in countries having a high mortality burden. Level of evidence: Level VI.

Health data ecosystem in Pakistan: a multisectoral qualitative assessment of needs and opportunities.

OBJECTIVE: Data are essential for tracking and monitoring of progress on health-related sustainable development goals (SDGs). But the capacity to analyse subnational and granular data is limited in low and middle-income countries. Although Pakistan lags behind on achieving several health-related SDGs, its health information capacity is nascent. Through an exploratory qualitative approach, we aimed to understand the current landscape and perceptions on data in decision-making among stakeholders of the health data ecosystem in Pakistan. DESIGN: We used an exploratory qualitative study design. SETTING: This study was conducted at the Aga Khan University, Karachi, Pakistan. PARTICIPANTS: We conducted semistructured, in-depth interviews with multidisciplinary and multisectoral stakeholders from academia, hospital management, government, Non-governmental organisations and other relevant private entities till thematic saturation was achieved. Interviews were recorded and transcribed, followed by thematic analysis using NVivo. RESULTS: Thematic analysis of 15 in-depth interviews revealed three major themes: (1) institutions are collecting data but face barriers to its effective utilisation for decision-making. These include lack of collection of needs-responsive data, lack of a gender/equity in data collection efforts, inadequate digitisation, data reliability and limited analytical ability; (2) there is openness and enthusiasm for sharing data for advancing health; however, multiple barriers hinder this including appropriate regulatory frameworks, platforms for sharing data, interoperability and defined win-win scenarios; (3) there is limited capacity in the area of both human capital and infrastructure, for being able to use data to advance health, but there is appetite to improve and invest in capacity in this area. CONCLUSIONS: Our study identified key areas of focus that can contribute to orient a national health data roadmap and ecosystem in Pakistan.

COVID-19 severity and cardiovascular outcomes in SARS-CoV-2-infected patients with cancer and cardiovascular disease.

Background: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. Objectives: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. Methods: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated. Results: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p<0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31-1.74] vs. OR 1.04 [95% CI 0.90-1.20], pinteraction <0.001). Conclusions: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701).

Leveraging COVID-19 vaccination to promote hepatitis C screening.

Health care initiatives, such as hepatitis C virus (HCV) screening, have been greatly overshadowed by the corona virus disease 2019 (COVID-19) pandemic. However, COVID-19 vaccination programs also provide an opportunity to engage with a high volume of people in a health care setting. We collaborated with a large COVID vaccination center to offer HCV point-of-care testing followed by dried blood spot collection for HCV RNA. Additionally, this opportunity was used to evaluate the practical significance of a 5-minute version of the OraQuick HCV antibody test in lieu of the standard 20-minute test. We tested 2317 individuals; 31 were HCV antibody positive and six were RNA positive of which four were treated and reached sustained virological response. Over a third of those surveyed said they would not have participated had the test required 20 minutes. Conclusion : Colocalizing HCV testing and linkage to care at a COVID vaccination clinic was found to be highly feasible; furthermore, a shortened antibody test greatly improves the acceptance of testing.

Urine eosinophil-derived neurotoxin: A potential marker of activity in select eosinophilic disorders.

BACKGROUND: Biomarkers of eosinophilic disease activity, especially in the context of novel therapies that reduce blood eosinophil counts, are an unmet need. Absolute eosinophil count (AEC) does not accurately reflect tissue eosinophilia or eosinophil activation. Therefore, the aims of this study were to compare the reliability of plasma and urine eosinophil major basic protein 1, eosinophil cationic protein, eosinophil-derived neurotoxin (EDN), and eosinophil peroxidase measurement and to evaluate the usefulness of eosinophil granule protein (EGP) measurement for the assessment of disease activity in patients with eosinophil-associated diseases treated with mepolizumab, benralizumab, or dexpramipexole. METHODS: Eosinophil granule protein concentrations were measured in serum, plasma, and urine from healthy volunteers and patients with hypereosinophilic syndrome (HES), eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic asthma using a multiplex assay. RESULTS: Urine EGP concentrations remained stable, whereas serum and plasma EGP concentrations increased significantly with delayed processing. Plasma (p) EDN, but not urine (u) EDN, concentration correlated with AEC and negatively correlated with prednisone dose. Both pEDN and uEDN decreased significantly following treatment of HES patients with benralizumab and EGPA patients with mepolizumab. uEDN appeared to increase with clinical relapse in both patient groups. CONCLUSIONS: Measurement of EGP in urine is noninvasive and unaffected by cellular lysis. Although plasma and urine EDN concentrations showed a similar pattern following benralizumab and mepolizumab treatment, the lack of correlation between AEC or prednisone dose and uEDN concentrations suggests that measurement of uEDN may provide a potential biomarker of disease activity in patients with HES and EGPA.

The impact of COVID-19 safety interventions on creating a controlled environment on campus.

Objectives: During COVID-19 the re-opening of educational institutes was frequently debated, however with the decline in the number of COVID-19 cases, The Aga Khan University (AKU) in Karachi, Pakistan opened its campus for medical and nursing students after more than 6 months of closure. To ensure gradual resumption of activities on-campus, a combination of interventions was diligently deployed to minimize student infection rates. Scarce literature exists on students' perceptions regarding decisions implemented by university leadership. The aim of the study was to determine the efficacy of these interventions. Methods: We conducted a convergent, parallel, mixed-methods observational study targeting medical and nursing students. An online questionnaire was disseminated to elicit students' degree of (dis)agreement on a four-point Likert scale. Focused group discussions (FGDs) were conducted to comprehend reasons for (dis)agreement. Results: Total of 183 students responded to questionnaire (59.0% nursing, 67.8% female), 11 FGDs were conducted with 85 students. Interventions with highest agreement were mandatory face masks policy (94.54%), weekly mandated COVID-testing (92.35%) and students' Academic Bubble (91.26%); highest disagreement was for Sehat Check application (41.53%); and stay strong campaign (40.44%). Four themes emerged from FGDs: Effective safety interventions, Safety interventions with limited effectiveness, Utility of Sehat Check Application and Future recommendations for informing policy. Conclusion: It is paramount to seek student-feedback at forefront of university re-opening strategy. Clear communication channels are as important as an administrative response system's robustness. Bidirectional communication channels are fundamental and requisite during ever-changing policies and regulations. Engaging student representatives in decision making or implementation processes (such as "pilot" before "roll-out") would allow any potential issues to be managed early on. Gather real-time anonymous feedback and identify key areas that need further promulgation and those that need to be replaced with more effective ones.

A comparative systematic scan of COVID-19 health literacy information sources for Canadian university students. / Analyse comparative systématique des sources d'information sur la littératie en matière de santé liée à la COVID-19 des étudiants universitaires au Canada.

INTRODUCTION: With the rapid spread of online coronavirus-related health information, it is important to ensure that this information is reliable and effectively communicated. This study observes the dissemination of COVID-19 health literacy information by Canadian postsecondary institutions aimed at university students as compared to provincial and federal government COVID-19 guidelines. METHODS: We conducted a systematic scan of web pages from Canadian provincial and federal governments and from selected Canadian universities to identify how health information is presented to university students. We used our previously implemented health literacy survey with Canadian postsecondary students as a sampling frame to determine which academic institutions to include. We then used specific search terms to identify relevant web pages using Google and integrated search functions on government websites, and compared the information available on pandemic measures categorized by university response strategies, sources of expertise and branding approaches. RESULTS: Our scan of Canadian government and university web pages found that universities similarly created one main page for COVID-19 updates and information and linked to public sector agencies as a main resource, and mainly differed in their provincial and local sources for obtaining information. They also differed in their strategies for communicating and displaying this information to their respective students. CONCLUSION: The universities in our sample outlined similar policies for their students, aligning with Canadian government public health recommendations and their respective provincial or regional health authorities. Maintaining the accuracy of these information sources is important to ensure student health literacy and counter misinformation about COVID-19.

Using Social Media as a Survey Recruitment Strategy for Post-Secondary Students During the COVID-19 Pandemic.

The COVID-19 pandemic rapidly forced Canadian post-secondary students into remote learning methods, with potential implications on their academic success and health. In recent years, the use of social media to promote research participation and as a strategy for communicating health messages has become increasingly popular. To better understand how the pandemic has impacted this population, we used social media platforms to recruit students to participate in a national bilingual COVID-19 Health Literacy Survey. The purpose of the survey was to assess the health literacy levels and online information-seeking behaviors of post-secondary students in relation to the coronavirus. This paper outlines the social media recruitment strategies used for promoting participation in the survey among Canadian post-secondary students during the pandemic. Facebook, Twitter, and Instagram accounts were created to promote the online survey. The objective of this paper is to examine the use of Instagram, Facebook, and Twitter as survey recruitment strategies tailored to students. Data analytics from these platforms were analyzed using descriptive statistics. We found that the most commonly used platform for survey dissemination was Twitter, with 64800 total impressions recorded over 3 months. The use of social media as a survey recruitment strategy showed promise in the current context of COVID-19 where many students are participating in online learning and for a study population that actively uses these platforms to seek out information.

Can Sound Public Health Policies Stem the Tide of Burgeoning Epidemic of Cardiovascular Disease in South Asians?

PURPOSE OF REVIEW: To revisit the importance of prevention strategies and policies in reducing the burden of ischemic heart disease in South Asian countries. RECENT FINDINGS: South Asia has seen rapid growth in its population with variable improvement in health indicators such as life expectancy at birth over the last three decades. Parallel to these improvements, there has been a stark rise in noncommunicable diseases (NCDs) but without a commensurate improvement in infrastructure/policies and health system interventions to address NCDs. South Asia is the epicenter of the cardiovascular disease (CVD) epidemic in Asia. It has a population that manifests accelerated atherosclerosis at a younger age. Poverty, lower health literacy, lack of health-promoting behaviors, poor urban design, rising air pollution, weak health systems, and lack and poor implementation of existing policies contribute to the continued rise in the incidence of CVD and the associated case fatality rates. A relatively young population presents an opportunity for implementation of prevention measures now which if not adequately utilized will result in an exponential rise in the CVD burden. There is a large gap between policymaking and implementation in this part of the world. Economic realities further constrain coverage of prevention policies; and therefore, stronger collaboration between governments, stakeholders, civil society, and regional and international funding agencies is needed to universally implement prevention strategies in South Asia.

Ethanolic extract of okra has a potential gastroprotective effect on acute gastric lesions in Sprague Dawley rats.

Okra (Abelmoschus esculentus) has various bioactive components used for the treatment of different diseases such as gastritis and ulcers. This research aims to examine the anti-inflammatory and anti-ulcer attributes of okra extract against gastric lesions. Adult Sprague Dawley male albino rats were divided into five groups. The negative control (G1) received normal feed, positive control (G2) received ulcer-inducing drug aspirin 150 mg/kg of body weight (b.w), G3 group received reference drug omeprazole 20 mg/kg of b.w, G4 group received okra extract 250 mg/kg of b.w, and G5 group received 500 mg/kg of b.w. Acute gastric damage was induced in G1, G2, G3, and G4 using aspirin 150 mg/kg of b.w, during 14-day-long efficacy trials after that all the animals were sacrificed. Anti-ulcer parameters and histopathological analysis of stomachs were performed to evaluate the degree of recovery against tissue damage by the administration of okra extract. The obtained results indicated that the 500 mg/kg of b.w okra extract exerted a protective effect in aspirin-induced gastric ulcers by significantly (p < .05) reducing ulcer score, ulcer area, total acidity, and gastric volume, and significantly (p < .05) increasing gastric pH. Moreover, histopathological observation revealed that gastric mucosa was normal in G1, G3, G4, and G5; however, disruptions in the gastric epithelium were observed in G2. Congestion was observed in all groups except G1 and G5. Gastric pits and gastric glands were increased in size in G2 and G4. A higher concentration of okra extract (500 mg/kg of b.w) showed almost similar results when compared to the reference drug omeprazole.

Celiac disease associated with aplastic anemia in a 6-year-old girl: a case report and review of the literature.

BACKGROUND: Celiac disease may present with hematological abnormalities including long-standing anemia. Both aplastic anemia and celiac disease have a similar underlying autoimmune process but an association between the two is seldom reported. There have only been three pediatric cases reporting this association and this case is the first reported in a female pediatric patient. CASE PRESENTATION: We report a case of 6-year-old South Asian girl presenting with bruises, petechiae, and recent history of loose stools. On evaluation, she was diagnosed as having celiac disease and was put on a gluten-free diet and further investigations including bone marrow biopsy revealed pancytopenia. She was managed with packed red cells, platelets, and diet restrictions and had improving platelet counts over yearly follow ups. Her parents were counseled regarding the need for bone marrow transplant. CONCLUSIONS: This is the fourth case report suggesting an association between celiac disease and aplastic anemia in the pediatric population and this association could be more common than expected. Timely intervention of either celiac disease through strict gluten-free diet or aplastic anemia through immunosuppressive therapy could potentially reduce the risk for other autoimmune conditions. We can see that all four pediatric cases reported with this potential association are from South East Asia and hence larger studies would be prudent to explore this association.

Impact of age, tumor size, lymph node metastasis, stage, receptor status and menopausal status on overall survival of breast cancer patients in Pakistan.

BACKGROUND: Survival of breast cancer patients depends on a number of factors which are not only prognostic but are also predictive. A number of studies have been carried out worldwide to find out prognostic and predictive significance of different clinicopathological and molecular variables in breast cancer. This study was carried out at Nuclear Medicine, Oncology and Radiotherapy Institute (NORI), Islamabad, to find out the impact of different factors on overall survival of breast cancer patients coming from Northern Pakistan. MATERIALS AND METHODS: This observational retrospective study was carried out in the Oncology Department of NORI Hospital. A total of 2,666 patients were included. Data were entered into SPSS 20. Multinomial logistic regression analysis was performed to determine associations of different variables with overall survival. P values <0.05 were considered significant. RESULTS: The mean age of the patients was 47.6 years, 49.5% being postmenopausal. Some 1,708 were ER positive and 1,615 were PR positive, while Her 2 neu oncogene positivity was found in 683. A total of 1,237 presented with skin involvement and 426 had chest wall involvement. Some 1,663 had > 5cm tumors. Lymph node involvement was detected in 2,131. Overall survival was less than 5 years in 669 patients, only 324 surviving for more than 10 years, and in the remainder overall survival was in the range of 5-10 years. CONCLUSIONS: Tumor size, lymph node metastases, receptor status, her 2 neu positivity, skin involvement, and chest wall involvement have significant effects whereas age and menopausal status have no significant effect on overall survival of breast cancer patients in Pakistan.

Epithelioid trophoblastic tumor: an unusual malignancy of ovary.

Epithelioid Trophoblastic Tumor (ETT) is a distinct but rare variety of gestational trophoblastic tumors. Misdiagnosis delays effective treatment and affects the survival. The case being reported here involved a 43 years old lady presented with 4 months history of intermenstrual per vaginal bleeding and 6 weeks amenorrhea. Workup has revealed pelvic mass. The patient underwent laparotomy with transabdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathology turned out to be clear cell carcinoma of the ovary. Patient was put on chemotherapy but there was progression of disease. Review of histopathology and immunohistochemistry revealed it as Epithelioid Trophoblastic Tumor; serum b-hCG was also raised. The case was really challenging for histopathologist. By the time final diagnosis was made, patient developed extensive metastases in lungs and liver and expired. Such an uncommon yet distinct trophoblastic tumor should be kept in mind by pathologists and treating physicians.

Adenocarcinoma of rectum as second primary cancer after treatment of endometrium cancer.

Colorectal cancer is the second leading cause of death from cancer in women in the United States. Previous epidemiologic studies have identified a 1.5 - 3 fold increased risk of colorectal cancer in women after ovarian and endometrial cancer. In Pakistan, neither such a study showing relationship of colorectal cancer with gynaecological cancer has been done nor any case has been reported. Here, a case is being reported who developed adenocarcinoma of rectum as the second primary about nine years after completion of treatment for adenocarcinoma of endometrium.