Challenges and solutions for developing countries in promoting global health and achieving SDG 3

The Sustainable Development Goal 3 (SDG 3), introduced by United Nations and supported by World Health Organization to ensure healthy lives and promote well-being for individuals of all ages, has become increasingly challenging to achieve. The COVID-19 pandemic has disrupted healthcare systems and overwhelmed medical resources, intensifying health inequalities worldwide. As a result, achieving SDG 3 has become more complex and difficult than ever before.1 The current state of global health reflects significant issues and gaps in achieving the SDG 3 targets. For instance, the global maternal mortality ratio, which only slightly decreased from 227 to 223 per 100,000 live births between 2015 and 2020, indicates insufficient progress towards the target of 70 per 100,000 by 2030. Additionally, while the under-five mortality rate dropped to 37 per 1,000 live births in 2022, and neonatal mortality decreased to 17 per 1,000 live births, significant disparities remain. The high rates of communicable diseases, with 1.3 million new HIV infections and 249 million malaria cases in 2022, highlight persistent global health threats. Drug treatment coverage fell from 11% in 2015 to under 9% in 2022, and vaccination rates for diphtheria, tetanus, pertussis and measles remain below pre-pandemic levels.2 These figures emphasize the need for intensified global efforts, increased investment, and focused interventions to address these disparities and achieve the SDG 3 targets.   Despite significant efforts and advancements by developed nations, the overall state and dynamics of global health are suboptimal. The focus on specific health-related challenges in these countries often overshadows critical issues in developing regions, such as the lack of new treatments for tuberculosis.3 This phenomenon impedes the collective effort required to address the global health inequities and delays progress toward achieving SDG 3 targets. The COVID-19 pandemic has demonstrated the interconnectedness of the world and shown that without active and robust participation from developing countries, achieving global health targets is extremely difficult.4,5 However, involving low- and lower-middle-income countries (LICs and LMICs) in building a more resilient global health framework is a gigantic task that requires addressing the unique challenges these nations face in achieving SDG 3.6 These countries are struggling with a range of health-related challenges, including poverty, inadequate access to clean water, maternal and child health issues, and increasing prevalence of infectious and non-communicable diseases.7 Additionally, access to healthcare is uneven, leading to significant disparities among different population groups, particularly in rural areas.8,9 A major hurdle in these countries is poor governance, which obstructs effective health management and appropriate resource allocation.10 This issue is further aggravated by the inadequate healthcare infrastructure, including insufficient facilities, outdated equipment, and a significant shortage of skilled health workers, resulting in compromised quality of care.11,12 A key factor exacerbating the situation is brain drain, driven by low salaries, poor working conditions, and limited career advancement opportunities, which compel healthcare workers to leave their home countries.13 Financial constraints exacerbate these problems, limiting the capacity to invest in and sustain essential health services.14 Additionally, despite facing significant challenges in achieving the SDGs, LICs and LMICs contribute minimally to research on local issues related to achieving the SDG 3 targets, highlighting a global misalignment.11  The existing health data from local research in LMICs often raises concerns about quality and accuracy, making it risky to rely on outdated or unreliable information for aggregation, estimation, and modeling.12,15-18 Addressing these complex challenges requires a coordinated strategy that leverages local strengths and fosters international cooperation. Advancing global health in developing countries demands a comprehensive approach, incorporating innovation, local research, and effective collaboration. The post-pandemic era calls for systematic solutions through reclassifying SDG priorities, coordinating resources, and promoting collaboration across economic, technological, cultural, and political sectors.19 Prioritizing local research and development is essential for tailoring interventions to the specific health needs of LICs and LMICs, where health issues may differ significantly from those in higher-income countries.11 Local research can provide valuable insights into the unique health challenges faced by communities. While, regional and multinational collaboration can strengthen the disease control, facilitate knowledge sharing, and promote collective solutions to common problems.20 Innovative financing mechanisms and broader access to affordable health insurance can significantly improve service delivery.21 Additionally, strengthening health information systems, and supporting local innovations tailored to specific needs can drive further progress.5 Tackling health inequities and investing in preventive care are crucial for reducing disparities and enhancing overall health outcomes.22 Such comprehensive efforts not only benefit local health systems but also make meaningful contributions to global health. No doubt, the journey toward achieving SDG 3 is loaded with challenges, particularly for developing countries. However, by strengthening healthcare systems, implementing good governance, fostering local research, and embracing international cooperation, these nations can overcome their own health challenges and make substantial contributions to the global health progress. The global community must recognize that the health of the world is interconnected, and the success of SDG 3 hinges on our collective efforts to support and uplift the most vulnerable populations

Biosafety challenges and the future landscape in Pakistan

Sepsis is a major threat to global health, as highlighted by the Global Burden of Disease Study, which recorded an estimated 48.9 million cases of sepsis globally, resulting in 11.0 million sepsis-related deaths, accounting for 19.7% of all global deaths in 2017. The incidence and mortality rates of sepsis are particularly high in sub-Saharan Africa, Oceania and South Asia.1 In developing countries, the increasing incidence of sepsis poses a significant challenge, emphasizing the imperative need to prioritize biosafety measures for public health protection. Ensuring biosafety is crucial for the safe handling of biological materials, safeguarding researchers, laboratory personnel, animals and the environment from infectious agents and toxins. In Pakistan, this critical need highlights the urgent requirement for robust biosafety frameworks, where establishing and maintaining these practices remains a formidable challenge.2 Pakistan has demonstrated its commitment to biosafety as a responsible state by being a party to the Cartagena Protocol on Biosafety (CPB) under the Convention on Biological Diversity (CBD).3 The Ministry of Climate Change, in coordination with National Food Security & Research and National Health Services Regulations & Coordination, is responsible for implementing the CPB.4 Additionally, under the Pakistan Environmental Protection Act 1997, the Pakistan Environmental Protection Agency (Pak-EPA) enacted the Pakistan Biosafety Rules in April 2005 to regulate Genetically Modified Organisms (GMOs).5 To facilitate compliance with these rules, the National Biosafety Guidelines were issued in October 2005.6 In April 2006, the National Biosafety Centre was established within the Pak-EPA to further strengthen the biosafety regulatory framework.7 Risk assessment standards and procedures are set by the National Biosafety Committee to ensure the safe handling and regulation of GMOs in Pakistan.8 However, despite these steps in the right direction, many laboratories across Pakistan, even in major cities, exhibit significant gaps in biosafety practices, including inadequate emphasis on laboratory biosecurity, absence of occupational health programs, and ineffective risk assessment strategies.9,10 A situational analysis by the national laboratory working group revealed key issues in national laboratory biosafety and biosecurity management, such as the absence of a centralized Biosafety and Biosecurity Management System, inadequate staff training and competency assessments, poor maintenance of protective equipment, improper waste disposal management, and insufficient fire prevention measures.11 In recent years, there has been positive progress in biosafety practices in Pakistan, significantly accelerated by the COVID-19 pandemic. The pandemic has catalyzed substantial improvements through heightened awareness, stringent protocols, infrastructure upgrades, strengthened regulatory frameworks, enhanced diagnostic capabilities, and increased collaboration. These advancements have led to better waste management, improved safety behaviors and comprehensive biosafety and biosecurity measures. Additionally, significant strides have been made in training programs and the provision of safety and health services.9,12 Nevertheless, despite dedicated efforts by Pakistan's science and policy leaders, Pakistan is facing challenges in biosafety and biosecurity like inadequate risk assessment frameworks, insufficient monitoring tools, lack of data on biosecurity hazards, integration difficulties with limited resources, and poor stakeholder coordination.13 To sustain and enhance these biosafety measures, ongoing efforts and investments are necessary. Looking ahead, the landscape of biosafety in Pakistan is poised for further advancements, driven by the invaluable lessons derived from the COVID-19 pandemic. Sustained investments in infrastructure, regulatory enhancements, and training initiatives will be crucial in elevating biosafety standards. Integration of advanced technologies like digital tracking systems and automated safety protocols, along with intensified international collaborations, will further strengthen biosafety practices. Additionally, fostering a culture of safety, ongoing education, and public awareness campaigns will be indispensable in ensuring the effective implementation and longevity of biosafety measures nationwide

Beyond COP: Pakistan's evolving role in a global climate context

The global community has diligently pursued the ambitious goals of the Paris Agreement 1 to address climate change. The upcoming 28th Conference of the Parties (COP) underscores the urgency of dealing with the climate crisis.2 Pakistan, with its decades-long experience in facing tangible effects like floods and droughts, is in a critical position. These natural disasters pose significant challenges to the country's environmental resilience and sustainability.3-5 Pakistan's vulnerability to climate change is evident, as emphasized by the increased frequency and severity of natural disasters. Alarmingly, Pakistan is globally ranked 8th in vulnerability to climate change impacts 6 and holds the 23rd position in the Inform Risk Index, signifying high disaster risk among 191 countries. 7 It highlights the crucial need for proactive and concerted efforts to address the unfolding climate crisis. Despite multifaceted limitations, Pakistan has the potential to contribute significantly. Limited financial resources hinder large-scale climate initiatives due to economic constraints.8 Simultaneously, the adoption of eco-friendly practices faces challenges due to obstacles arising from infrastructure gaps and technological constraints.9 Nevertheless, Pakistan's meaningful involvement in global climate solutions remains vital. The nation's distinctive perspectives, creative innovations, and steadfast commitment are invaluable assets in enriching the global effort against climate change.   Pakistan initiated its National Climate Change Policy in 2012,10 later refining it in 2021 for more effective addressing of ongoing climate challenges.11 Adopting a multidimensional approach, the policy emphasizes community-based initiatives and sustainable agricultural practices to enhance resilience. It also prioritizes mitigation and adaptation strategies, promotes renewable energy, and encourages international collaboration to address the evolving climate crisis.11 In response to urgent climate challenges, Pakistan employs a comprehensive strategy involving various approaches, from nature-based solutions to technology-driven interventions. 12 The country is committed to a renewable energy transition, accelerating the adoption of solar and wind power to reduce carbon emissions. Initiatives like the 'Ten Billion Tree Tsunami Programme' and the Prime Minister’s 'Urban Forest Project' reflect Pakistan's dedication to large-scale afforestation and sustainable urban development. The 'Ten Billion Tree Tsunami Programme' aims to capture 148.76 million metric tons of carbon dioxide equivalent emissions in the next decade. The financing for this initiative comes from domestic sources, amounting to an estimated expense of $800 million. 12 This reflects Pakistan's commitment to addressing environmental concerns using indigenous resources. Despite facing challenges with a vulnerable water infrastructure leading to substantial water loss, Pakistan is implementing initiatives for water management and conservation. The "decade of dams," as designated by the ‘Water and Power Development Authority’ (WAPDA), involves constructing five dams. These include ongoing projects like ‘Diamer-Bhasha Dam’ and ‘Mohmand Dam’, along with three hydropower projects and one canal & water supply project.  This comprehensive plan, set to be implemented between 2023 and 2029, aims to elevate water storage by over 24 million acre-feet. 13 The success of these endeavors would significantly contribute to addressing water-related challenges in the country. Adoption of climate-smart agriculture practices, including innovative technologies and management changes, is already underway, aiming to enhance resilience and sustainability.14 Securing diverse financing, implementing pro-poor policies, and empowering institutions are vital for the transformative impact of climate-smart agriculture. Additionally, investing in research for climate-resistant crops contributes to addressing local and global climate challenges. Urban planning integrates green spaces and energy-efficient infrastructure for climate-resilient cities. Community-based adaptation strategies acknowledge local vulnerabilities and traditional knowledge. Robust educational programs are implemented to promote public awareness. These programs also encourage the adoption of sustainable practices. Pakistan actively pursues international collaboration, leveraging partnerships for knowledge sharing and technology transfer.15,16 Green finance mechanisms drive investments into sustainable projects, and waste management initiatives minimize environmental impact. Climate-resilient infrastructure is designed to withstand extreme weather events, reflecting Pakistan's commitment to navigating climate change with determination.17 Regional collaboration is crucial for addressing shared climate challenges. The emphasis lies on collaboration between Pakistan and other ‘South Asian Association for Regional Cooperation’ (SAARC) nations, with particular attention to neighboring countries, especially India. Regrettably, the SAARC action plan on climate change, 18 adopted at the SAARC Ministerial Meeting on Climate Change in Dhaka, has not been fully implemented. Strengthened collaboration within the SAARC framework can serve as a positive model for transboundary action, creating global impact in addressing climate change. In summary, Pakistan is at the forefront of global climate action, spearheading initiatives such as the ‘Ten Billion Tree Tsunami Programme’ and the Prime Minister’s ‘Urban Forest Project.’ Despite challenges, the nation's commitment to sustainability is evident in its comprehensive approach, including local initiatives, sustainable agriculture, and international collaboration. With a focus on resilience and innovative solutions, Pakistan can emerge as a crucial player in shaping a greener and more sustainable world

CLINICAL RESEARCH IN PAKISTAN: PAST, PRESENT AND FUTURE PROSPECTS

Pakistan is the 5th most populous country in the world with a population of 229.5 million in 2022.1 Like any developing country, Pakistan is facing various health-related challenges with a huge burden of communicable and non-communicable diseases, poor indicators of maternal and newborn health, nutrition and life expectancy.2,3 Pakistan has a unique population with diverse genetic, lifestyle, socioeconomic, cultural and environmental factors that can affect the disease burden, progression, and response to treatment. Local clinical research is required to understand these factors and develop healthcare interventions tailored to the needs of the Pakistani population. This targeted approach will not only be helpful in addressing the local problems but will have a regional and global impact, especially for other developing countries. First documented evidence of clinical trials from Pakistan, available on PubMed can be traced back to 1963-1964, when Cholera vaccine field trials were conducted in East Pakistan.4,5 Pubmed search revealed that four clinical trials were published in 1968, forty trials were published from 1969-1990, 152 trials were published from 1991-2000, 403 from 2001-2010 and 2737 trials were published from 2011 till February 2023.6   Clinical trials registration with any one of the primary registries by World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP)7 is required by for publication of all clinical trials.8 Unfortunately, clinical trials registration is not done for all trials being conducted in Pakistan. However, data of clinicaltrials.gov showed 2231 clinical trials registered from Pakistan till March 01, 2023; 1895 were Interventional studies, 1471 studies were completed studies, 395 were recruiting, 61 studies were active-not recruiting studies and 66 studies were not-yet recruiting studies.9 Clinical trials from Pakistan registered with Iranian Registry of Clinical Trials (IRCT) and Australian New Zealand Clinical Trials Registry (CTR) till March 01, 2023, were 355 and 164 respectively.10,11 Although the only local CTR of Drug Regulatory Authority of Pakistan (DRAP) is still not included in the list of primary registries by WHO ICTRP. DRAP website shows only 36 clinical trials registered with CTR of DRAP (list of approved clinical trials and studies, updated on DRAP website is till 30th May, 2022).12                                          Evidence is suggestive of an increasing trend in the number of clinical trials registered from Pakistan.13 However, despite of having a large population, sharing a significant pool of patients and rapidly growing pharmaceutical market, Pakistan sharing only 0.1% of the global clinical trials, is not comparable to its real capability.14 Main factors that may impede the output of clinical trials in Pakistan, like other developing countries include inadequate infrastructure, insufficient resources, limited trained and skilled researchers, lack of funding, lack of effective collaboration, poor quality assurance and regulatory barriers.15 Pakistan faces a shortage of research infrastructure, required to conduct of the clinical trials in a safe, effective, and efficient manner. Currently well-equipped laboratories and advanced research facilities are only available in major tertiary care hospitals, medical universities and other research institutes. DRAP requires mandatory approval of Clinical Trial Site(s) (CTS) for conducting clinical trials in Pakistan.16 As per available information on DRAP website, total 82 CTS (49 trial specific & 33 Generalized) are approved by DRAP (List of approved CTS updated till 30th May, 2022). Out of 82 CTS, 34 were from Panjab, 33 from Sind, 7 from Islamabad and 4 each from Khyber Pakhtunkhwa and Baluchistan.17 Majority of centers are lacking important resources like clinical trial management systems, data management & analysis, electronic medical record, electronic source document verification and internet connectivity etc.18 Limited trained and skilled researchers and shortage of qualified research assistants and support staff is another challenge faced by Pakistan.  According to WHO, Pakistan has 5,185 full time equivalent health researchers, 7% of all researchers from WHO Eastern Mediterranean region.19 Similarly, lack of funding for health research has negative effects on magnitude, quality and scope of clinical research in Pakistan. According to the latest report of World Research and Innovation Transformation (World RePORT), low-income countries received about 0.2% of the annual grant amount. Pakistan received 17.6 Million USD (9.39% of 188 countries) as compared to 38.57 Million USD by India.20 Researchers are spending out of pocket money to conduct doctorate level research in Pakistan. Unfortunately, there is no FDA approved pharmaceutical company in Pakistan that can invest in clinical research and conduct multi-center clinical trials.18 Poor quality assurance in clinical trials is another major impediment to the progress of clinical research. Issues related to research ethics committees, poor adherence to study protocol and nonexistence of research integrity offices in universities/research institutions lead to uncertainty about the credibility and trustworthiness of research process and deter international collaboration.   DRAP is doing excellent job in regulating clinical research and safeguarding the rights of research participants. However, certain policies of DRAP create additional obstacles for national and international collaboration in clinical research. Main barriers include mandatory approval of all clinical trials from national bioethics committee, lengthy approval processes complicated with inordinate delays, unclear regulatory requirements, and limited resources to enforce regulations.14,16 Despite of all these challenges and concerns, the future of clinical research in Pakistan is quite promising. Establishment of dedicated clinical trials units at the major research institute and universities in Pakistan is the major development in this regards.18 Master’s in Bioethics is a great step taken by Center of Biomedical Ethics & Culture, Karachi Pakistan.21 International Conference on Harmonization- Good Clinical Practice (ICH-GCP) are also being offered by universities and research institutes to the investigators of clinical trials. Medical universities may boost the efforts of producing more skilled researchers by starting Master programs in clinical research. An important contribution is being extended by Association of Pakistani Physicians of North America (APPNA) in the form of APPNA- Medical Education, Research, International training and transfer of Technology (MERIT).22 APPNA MERIT provides learning opportunities for medical professionals and students in Pakistan, on the latest developments in medical research and practice through weekly webinars by leading experts in the field. APPNA MERIT has recently taken a great initiative bringing together all key stakeholders from Pakistan, United States and Canada to establish a strong network for strengthening clinical research in Pakistan. They held their first roundtable national consultation for evolving participatory clinical research ecosystem in Pakistan on Saturday 18th February 2023. Hopefully, a local (Pakistan) chapter of Association of Clinical Research Professionals (ACRP) will be established soon to provide networking and training support to clinical researchers from Pakistan.   Funding is a grave concern, especially during the current financial crises in Pakistan, resulting in a major cut in research grants to higher education institutions. Multifaceted approach is needed to look for national and international funding bodies, government & private non-profit organizations, agencies, foundations and pharmaceutical companies that can provide grants or funding for clinical research in developing countries addressing the priority issues of our local population. Researchers should explore potential collaborations with pharma industry and international researchers who are interested in outsourcing of clinical trials in developing countries. To attract international trials, we need to train our researchers, simplify regulatory approval, strengthen our pharmacovigilance system, and ensure strong ethical considerations. For national collaboration, establishing a strong network of clinical research organizations and institutions along with a Society for Clinical Research Sites in Pakistan is direly needed. Hopefully these measures will bring a positive change in the future landscape of clinical research in Pakistan

HEALTH AND PEACE: GLOBAL, REGIONAL AND LOCAL PERSPECTIVE

Over the last few decades, human beings are facing the worst challenges of violence, terrorism and wars apart from health related challenges. Health and peace are the fundamental rights of every human being and are interlinked. Relationship between health and peace is dynamic and bilateral. Peace is an important determinant of health while attainment of peace depends upon health of all people.1-3 Both health and peace have a very broad meaning. World Health Organization (WHO) defined health as “a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity”.3 Similarly, “peace” is currently taken as not just the absence or reduction of war but include negation of violence, presence of harmony, justice, equity; and the capacity to handle conflict in a nonviolent manner.4 Global peace is under threat by various conflicts, violence, terrorism and wars. During second half of 20th century, power game among superpowers resulted in open warfare, cold wars and proxy wars, leading to violent conflicts across the world. Worldwide, conflicts arising from any geopolitical, ethnic, religious and economic matters are handled either by a nonviolent peaceful way or through violence and wars. The use of violence for conflict resolution and peace building is not justified as violence itself is considered as opposite to peace and peace should only be achieved by peaceful means. 5,6 Violence, civil wars and terrorism are major threats to global health. Along with economic and infrastructural damage, wars contribute to increased mortality and morbidly with detrimental effects on physical and psychological health of the population.7 According to Global Burden of Disease Study, wars will be the 8th leading cause of disability and death by 2020.8 Iraq war led to the loss of 1,16,903 Iraqi civilians and more than 4,800 coalition military personnel from 2003-11.9 In Afghanistan, conflict and terrorism is the leading cause of disability-adjusted life years (DALYs) lost.10 Pakistan is also affected by violent conflict with an increasing trend over the last couple of decades.11 This resulted in 63,554 deaths in Pakistan from 2000-2018.12 The economic burden on Pakistan due to incidents of terrorism from 2001-20018 was US$126.79 billion.13 Achieving the goal of desirable standard of health for all people needs sustainable, long-term peacebuilding measures by reducing all forms of violence and wars. United Nations General Assembly in its resolution no 34/58 stated: “Peace and security, in their turn, are important for the preservation and improvement of the health of all people, and that cooperation among nations on vital health issues can contribute importantly to peace”.14 This gigantic task needs a multidisciplinary approach and cannot be achieved without involvement of the health professionals - as highlighted by WHO- resolution number 34.38 in 34th World Health Assembly.15 Various organizations like “International Committee of the Red Cross”, “International Physicians for the Prevention of Nuclear War”, “International Campaign to Ban Landmines” and others have worked on the involvement of health force in peace building process.16 In 1984, Pan American Health Organization (PAHO), introduced the concept of “Health as a Bridge for Peace (HBP)”17 which was later on adopted by WHO in 1998 during 51st World Health Assembly.18 HBP aimed to support the health workers in providing healthcare services in conflict affected zones and simultaneously avail all the opportunities to promote peace through various health related activities.19 Health related initiatives are not only helpful in reducing morbidity and mortality during wars but can also be useful in prevention, resolution and transformation of conflicts before, during and after violent conflicts and wars. “Peace through health (PtH)” is another important peace work initiative from McMaster University, addressing the role of health workers in promoting peace through various health interventions in context of war and conflict.16,20,21 “PtH working group has identified various mechanisms that can explain the peace-work performed by health-workers.21,22 Health professionals are already equipped with knowledge, certain skills, values and qualities that can be utilized in handling violent conflicts and promotion of peace in many situations.5,16 Like any other program, there are some limitations of PBH & PtH programs as well. There is no evidence-based, systematic evaluation of the impact of peace through health initiatives.16, 23 Some quarters advocate that health professionals are only concerned with health care delivery in war-affected areas and should not be involved in conflicts and peacebuilding process. Neutrality and impartiality of healthcare workers in certain situations can also be compromised. Questions are also being raised regarding formal education and appropriate skills of health care workers in conflict management and peace-building process.16, 24-26 However, the usefulness of peace through health theory has not been refuted through solid evidence. 20 As already discussed, South Asian region, including Pakistan and Afghanistan are confronting violent conflicts, wars and terrorism during the recent past. There is a dire need of seeking every opportunity to achieve and promote peace in Pakistan, Afghanistan and the region. The involvement of health professionals in this highly needed and noble cause is a proven and viable strategy. A strategic plan may be developed for integration of health-care delivery system with the prevention and transformation of violent conflicts and wars. Special peace-based training courses should be arranged for health care providers in war affected areas and high intensity conflict zones. Incorporation of peace and conflict studies in undergraduate medical curriculum and postgraduate public-health curriculum at university level will be a way forward in achieving peace through health in Pakistan and the region

Shared health challenges, political divides: can South Asia heal itself?

South Asia, with a population of 2.078 billion people (25.29% of the global population),1 is facing challenges in achieving Sustainable Development Goal (SDG) 3 targets, with most countries scoring around 60% on the SDG 3 index. 2  This region, accounting for a substantial share of global health issues, presents challenges that extend beyond its borders, affecting international health policies and economic stability. The region faces a dual burden of communicable and non-communicable diseases (NCDs). In 2019, it accounted for nearly half of all global cases of drug-susceptible tuberculosis and multidrug-resistant tuberculosis.3 By 2023, India (26%) and Pakistan (6.3%) were among the five countries contributing for 56% of global TB cases. 4 Similarly, NCDs, such as diabetes mellitus, stroke, and heart diseases, are highly prevalent in South Asia, with India and Pakistan among the leading contributors to the global diabetes burden. 5-7 Maternal and child health challenges also persist in South Asia, with only 46% of women receiving comprehensive maternal and neonatal health services, with Afghanistan reporting the lowest coverage at 2.8%.8 Antenatal care utilization remains low, with no significant improvement across SAARC countries from 2015 to 2030.9 The region continues to have one of the highest maternal mortality ratios, with significant disparities; for instance, the Maldives reports high antenatal care utilization (96.83%) compared to Bangladesh (47.01%).10  This analysis highlights that, despite individual country efforts to drive change, South Asia has collectively fallen short of achieving its regional health targets. The impact of COVID-19 further exacerbated the situation, emphasizing the urgency of addressing these challenges. Progress remains hindered by many factors like weak health systems, socio-economic inequities, poor governance, environmental challenges, rising disease burden, and barriers to healthcare access and quality. 11-14 Beyond these structural challenges, health progress in South Asia is further adversely affected by poor regional cooperation, driven by geopolitical disputes, religious conflicts, and deep-rooted mistrust among member nations.15,16 Ongoing military tensions between India and Pakistan, along with civil unrest in Afghanistan and Sri Lanka, have severely impacted public health initiatives and resource allocation across South Asia. Political instability and regional conflicts disrupt healthcare services by diverting resources from essential medical care, leading to reduced access and underutilization of healthcare facilities. Economic instability further burdens both patients and health systems, as poor-quality care increases out-of-pocket expenses, delays treatment, and worsens health outcomes. Strengthening health infrastructure and ensuring stability are crucial to mitigating these effects and improving healthcare indicators.17,18 The division of South Asia into two separate WHO regions—South-East Asia Region (SEAR) and Eastern Mediterranean Region (EMR)—remains a major barrier to regional health collaboration. Influenced by geopolitical tensions, such as Pakistan’s placement in EMRO due to its disputes with India,19 this structure has undermined India-Pakistan health cooperation, limiting collaboration, disease control, and resource sharing. The SEAR-EMRO divide further weakened the region’s COVID-19 response; while India’s vaccine production supported SEAR countries, Pakistan and Afghanistan (EMRO) faced high-cost import dependency and limited access. Disrupted supply chains and lack of cross-border coordination led to delays and deepened disparities.20,21 A unified, regionally grounded approach could strengthen health cooperation, policy integration, and public health outcomes across South Asia. Established in 1985, the South Asian Association for Regional Cooperation (SAARC) aimed to foster economic growth, social progress, and regional collaboration, including in health. However, geopolitical tensions, particularly between India and Pakistan, have largely rendered it ineffective, with many viewing it as defunct.22 Meanwhile, China’s growing influence in South Asia’s health sector, especially through COVID-19 vaccine diplomacy, has intensified regional competition, challenging India’s "Neighbourhood First" policy.23 Pakistan’s partnership with China through the China-Pakistan Economic Corridor (CPEC) has expanded into healthcare through the China-Pakistan Health Corridor, promoting bilateral investment and infrastructure development. 24Additionally, Bangladesh and Pakistan have shown signs of diplomatic revival, 53 years after Bangladesh’s independence.25 Given these shifting dynamics, reviving SAARC has become a timely and strategic imperative. While India’s re-engagement remains cautious, there are signs of evolving perspectives amid changing geopolitical and health landscapes.26 Lessons from regional models like the European Union (EU) and Association of Southeast Asian Nations (ASEAN), which have successfully pursued collaborative public health strategies despite internal divides, demonstrate that regional cooperation is both feasible and essential.27 Given the current health crises and deep trust deficit among South Asian nations, there is an urgent need for multilateral engagement to pursue the shared goal of health for all South Asians. Countries must set aside political reservations and commit to both short- and long-term strategies, such as establishing a regional health task force, revitalizing the SAARC Development Fund for joint financing, and developing a shared resource framework to strengthen health systems collectively. International support from organizations such as the World Health Organization and UNICEF can further boost these efforts, but the region must first take ownership through self-help and coordinated action. There is also a pressing need to prioritize research on shared health challenges, a trend reflected in leading global journals like BMJ and The Lancet, which have featured special issues and articles on strengthening regional health systems in South Asia.  Health diplomacy must now take the lead—not only to improve healthcare delivery—but to serve as a bridge to peace and cooperation in the region. The active involvement of civil society, media, and public advocacy is vital to holding government’s accountable and driving meaningful change. Now is the time to act—not only for better health—but for the long-term stability and future of South Asia

Advancing mental health assessment: indigenous psychometric tools for personality disorders in Pakistan

Mental disorders are widespread globally, impacting nearly 1 billion people, with 1 in 8 individuals living with a mental disorder, and costing the global economy trillions of dollars.1,2 The high burden of mental illness emphasizes the urgent need for improved mental health services. However, mental health service utilization varies significantly, from 33% in high-income countries to just 8% in low- and lower-middle-income countries (LMICs), where minimally adequate treatment ranges from 23% to 3%.3 Despite their high burden, LMICs face substantial gaps in mental health service availability, exacerbated by a lack of local research. Although the field of mental health has advanced significantly in recent years, the development of culturally relevant assessment tools remains a critical challenge in many non-Western contexts.4 This gap highlights the importance of cultural psychiatry, which emphasizes understanding mental health within the framework of local cultural, social, and linguistic contexts. The lack of such culturally informed tools has contributed to the underdiagnosis of mental illnesses, including psychological and personality disorders, further deepening the mental health crisis in these regions.4-6 Personality disorders, recognized as a global mental health priority, show significantly higher prevalence rates in high-income countries (9.6%) compared to LMICs.7 However, these figures may not accurately reflect the true burden of personality disorders, as existing diagnostic tools, primarily developed in Western contexts, are often adapted for use in non-Western populations without considering cultural variations in behavior, expression, and interpretation. This lack of cultural sensitivity increases the risk of misdiagnosis and underrepresentation of culturally specific manifestations of personality disorders. This accentuates the need for validated, indigenous diagnostic tools tailored to local populations and developed in national languages to ensure accurate diagnosis of personality disorders in LMICs. Addressing this critical gap, this thematic issue introduces ten meticulously developed Urdu-language scales for diagnosing various personality disorders. The development of these tools ensures assessments that are both linguistically precise and culturally relevant, bridging a significant gap in mental health diagnostics in non-Western contexts.  This issue features a comprehensive set of scales addressing a wide range of personality disorders, including Schizotypal, Schizoid, Paranoid, Histrionic, Obsessive-Compulsive, Dependent, Narcissistic, Antisocial, Avoidant, and Borderline Personality Disorders Developed by researchers Saima Rasheed and Zakia Bano, these instruments are the result of meticulous research and robust psychometric validation. Each scale follows a structured development process, beginning with item generation based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)8 and relevant literature, followed by expert evaluation, pilot testing, and advanced statistical analyses such as exploratory and confirmatory factor analyses (EFA and CFA). Expert panels of bilingual clinical psychologists ensured the cultural and linguistic relevance of the items. The pilot testing phases provided critical insights, with problematic items revised or discarded based on statistical performance and participant’s feedback. Through rigorous EFA and CFA, the final versions of these scales demonstrate strong reliability, validity, and a coherent factor structure, making them valuable tools for both clinical and research applications. The availability of these validated Urdu-language scales represents a major breakthrough for mental health in Pakistan, equipping clinicians with culturally tailored tools for accurate diagnosis, personalized treatment, and effective intervention in personality disorders. Researchers can utilize these scales to study prevalence, etiology, and treatment outcomes, enriching global literature on personality disorders. Moreover, these tools can inform public health initiatives to raise awareness, reduce stigma, and promote early identification and intervention, ultimately enhancing mental health outcomes. The publication of this special issue aligns with Khyber Medical University's commitment to promoting mental health in Pakistan and reflects the scope of KMUJ in advancing this critical field. This issue marks a significant milestone in mental health assessment by introducing culturally relevant, psychometrically robust tools for diagnosing personality disorders, addressing the gap in mental health resources for Urdu-speaking populations. The collaborative efforts of researchers, clinicians, and institutions highlighted here emphasize the value of local solutions to global challenges. We commend the authors for their dedication and innovation in addressing this pressing need and encourage further efforts to refine and expand these tools for broader applicability. This achievement highlights the transformative impact of culturally adapted mental health assessments in enhancing understanding, diagnosis, and outcomes for individuals with personality disorders in Pakistan and beyond. We also encourage researchers to actively use, validate, and refine these scales to ensure their continued improvement and effectiveness

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication