University of Lancaster

A four-year research project by INSEAD and five other institutions sheds light on how understanding medical criticality, supply chain risk and their interactions could help us better address drug shortages. FONTAINEBLEAU, France, SINGAPORE and SAN FRANCISCO, July 18, 2024 /PRNewswire/ -- Drug shortages are becoming an increasing problem in Europe and other parts of the world. When pharmacists in France walked out of their counters en masse and marched into the streets on 30 May, it was not just over their compensation and prospects, but a concern with wider implications for the public – the unreliable supply of drugs. In the Netherlands, the estimated annual total cost of drug shortages was about EUR220 million in 2023. In England, pharmacists have warned that drug shortages are at such critical levels that patients are at risk of immediate harm and even death. While Covid-19 shone the spotlight on drug shortages, it's a structural issue that exists even in the absence of demand and supply shocks. Yet most shortages are managed reactively, without accounting for the importance of supply chain risk. There needs to be a simple way to think about the differences between drugs and how that would lead to different interventions in addressing shortages. As a path to resolving these issues, Luk Van Wassenhove, Emeritus Professor of Technology and Operations Management and Iman Parsa, postdoctoral researcher at the Humanitarian Research Group at INSEAD, together with researchers* from Tilburg University, BI Norwegian Business School, Norwegian Institute of Public Health, Lancaster University and the Rotterdam School of Management embarked on a four-year project to study drug shortages in six European countries. Under the "Measures for Improved Availability of Medicines and Vaccines" (MIA#): funded by the Research Council of Norway, an analysis of Belgium, France, Norway, Sweden, The Netherlands and the UK led to the development of the Risk/Criticality Matrix (RCM). It represents a pragmatic framework for classifying drugs and guiding decision-making through a two-dimensional matrix: Supply chain risk (e.g. exported vs. locally produced drug) vs. medical criticality (e.g. blood thinners vs. erectile dysfunction drug). Refer to the Figure: Risk/Criticality Classification Matrix developed under the Measures for Improved Availability of Medicines and Vaccines (MIA) project. Drug supply chains involve many stakeholders with potentially vastly different perspectives, incentives and objectives. The simple, visual matrix is a powerful tool to align diverse stakeholders – particularly policy makers and international organisations – to consider how medical criticality and supply chain risk interact dynamically. Taking into consideration the context, regulations and costs, the tool can help them to determine the most appropriate intervention that is affordable, and which will not jeopardise patient care. The Risk/Criticality Classification Matrix is a first step in a continuous improvement loop that ensures interventions stay effective and aligned as conditions change, such as when a pandemic strikes or when a brand-name drug becomes generic. Ultimately, a systems approach is needed to tackle the chronic drug shortage issue, exacerbated by the complexity and sometimes opaqueness of drug supply chains. An evidence-based approach that aligns stakeholders and brings clarity might eventually heal medical supply chains of their structural woes. *Collaborators of the projects are: Thomas Breugem, Tilburg University; Iman Parsa and Luk Van Wassenhove, INSEAD; Kim van Oorschot and Marianne Jahre, BI Norwegian Business School; Christine Oline Årdal, Norwegian Institute of Public Health; Nonhlanhla Dube and Kostas Selviaridis, Lancaster University; and Harwin de Vries and Stef Lemmens, the Rotterdam School of Management. #More information on the MIA project: For any queries, reach out to [email protected] SOURCE INSEAD

The genetic disease Huntington's not only affects nerve cells in the brain but also has widespread effects on microscopic blood vessels according to research. These changes to the vasculature were also observed in the pre-symptomatic stages of the disease, demonstrating the potential for this research for predicting brain health and evaluating the beneficial effects of lifestyle changes or treatments. Huntington's disease is an inherited genetic condition leading to dementia, with a progressive decline in a person's movement, memory, and cognition. There is currently no cure. The genetic disease Huntington's not only affects nerve cells in the brain but also has widespread effects on microscopic blood vessels according to research. These changes to the vasculature were also observed in the pre-symptomatic stages of the disease, demonstrating the potential for this research for predicting brain health and evaluating the beneficial effects of lifestyle changes or treatments. Huntington's disease is an inherited genetic condition leading to dementia, with a progressive decline in a person's movement, memory, and cognition. There is currently no cure. The study, published in Brain Communications, is by Juliane Bjerkan, Gemma Lancaster, Peter McClintock and Aneta Stefanovska from Lancaster University, Jan Kobal, Sanja Šešok and Bernard Meglič from the University Medical Centre in Ljubljana, Karol Budohoski from the Cambridge University Hospitals NHS Trust, and Peter Kirkpatrick from Cambridge University. The team investigated changes in the coordination between neuronal activity and the brain's oxygenation in Huntington's disease. The vasculature and brain work together to ensure that the brain receives sufficient energy. In fact, the brain needs as much as 20% of the body's energy consumption despite only weighing approximately 2% of the body's weight. The "neurovascular unit" consists of vasculature connected via brain cells called astrocytes to neurons and ensures that this cooperation is successful. To assess the function of these neurovascular units, the researchers combined non-invasive measurement techniques and novel analysis methods developed by Lancaster's Nonlinear and Biomedical Physics group. Probes emitting infrared light were placed on the heads of participants in the study. The infrared light penetrated the skull harmlessly and enabled researchers to measure the brain's blood oxygenation. Electrodes, which can measure electrical activity from neurons, were also placed on the heads of participants. The researchers then studied the many rhythms related to the functioning of the brain and the cardiovascular system using mathematical techniques. These rhythms included the heart and respiration rates, related to the transport of nutrients and oxygen, as well as slower rhythms associated with local control of blood flow. Brain activity manifests in faster rhythms. Efficient functioning of the brain depends on how well all these rhythms are orchestrated. To assess the efficiency of the neurovascular unit, both the strength and the coordination of these rhythms were assessed by computing their "power" and "phase coherence." Professor Aneta Stefanovska of Lancaster University said: "We are hopeful that the method described could be used to monitor the disease progression and to evaluate the effect of potential treatments or lifestyle changes in Huntington's disease and other neurodegenerative diseases. We also hope that our study will stimulate new treatments of Huntington's disease targeting the vasculature and brain metabolism."

Scientists have discovered a new snakebite treatment to prevent the devastating tissue damage caused by African spitting cobra venom. Spitting cobra venom is incredibly potent and causes dermonecrosis, which presents as rapid destruction of skin, muscle and bone around the site of the snakebite, and can lead to permanent injuries and disfigurements, including limb loss and amputations in extreme cases. Using the repurposed small molecule drug varespladib to block one of the two major dermonecrosis-causing toxins in spitting cobra venom prevents skin and muscle damage. Each year, it is estimated that snakebite causes long term detrimental effects in around 400,000 people across the world, with a substantial proportion of those in Africa the result of spitting cobra bites. Scientists have discovered a groundbreaking new snakebite treatment to prevent the devastating tissue damage caused by African spitting cobra venom. Spitting cobra venom is incredibly potent and causes dermonecrosis, which presents as rapid destruction of skin, muscle and bone around the site of the snakebite, and can lead to permanent injuries and disfigurements, including limb loss and amputations in extreme cases. Professor Nicholas Casewell and Liverpool School of Tropical Medicine colleagues including Dr Steven Hall -- who is now at Lancaster University- discovered that using the repurposed small molecule drug varespladib to block one of the two major dermonecrosis-causing toxins in spitting cobra venom prevents skin and muscle damage. Each year, it is estimated that snakebite causes long term detrimental effects in around 400,000 people across the world, with a substantial proportion of those in Africa the result of spitting cobra bites. Currently, there is no effective treatment for tackling severe local envenoming caused by spitting cobra venom. Existing antivenoms only work on bites by other snake species and are often ineffective for treating local envenoming because antivenom antibodies are too large to effectively penetrate into the region around the bite site. Professor Nicholas Casewell of LSTM said: "Our findings hold much promise to improve the treatment of tropical snakebite. Current treatments for spitting cobra bites are widely regarded as being ineffective, meaning that rates of disability and amputation have remained high across much of Africa. Our data shows that blocking just one of the main toxin families in spitting cobra venom will likely prevent the debilitating tissue damage seen in thousands of snakebite patients each year." Professor Casewell's team, led by PhD student Keirah Bartlett and Dr Steven Hall, then of LSTM and now at Lancaster University, and also involving researchers from Canada, Denmark, Costa Rica and the USA, first analysed spitting cobra venom to identify the toxins responsible for causing venom-induced dermonecrosis. The results showed that cytotoxic three-finger toxins (CTx) are largely responsible but that phospholipases A2 (PLA2) toxins play a critical role in the process. Local injection of the PLA2-inhibiting drug varespladib reduced the extent of dermonecrosis, even when delivered up to an hour after the venom, and the protection conferred by the drug also extended to venom-induced muscle toxicity. According to the authors, the findings suggest that varespladib could become an invaluable treatment against the tissue-damaging effects of black-necked and red spitting cobra venoms, which cause extensive morbidity in snakebite victims across the African continent. Lead author Keirah Bartlett said: "These findings are extremely promising, not only does this offer up a new mode of treatment where previously nothing effective existed, but because varespladib has already gone through testing in human clinical trials, including for snakebite, it could be available for use in real world patients very soon." Dr Hall added: "Snakebite is a devastating neglected tropical disease, with tissue destruction caused by necrotic snake venoms permanently injuring hundreds of thousands of victims every year. Our work shows that the repurposed drug, Varespladib, is incredibly effective at inhibiting such necrosis caused by African spitting cobras; an exciting finding as their venoms are particularly fast-acting and destructive. We hope this work helps pave the way to future snakebite therapies that can save the lives and limbs of victims worldwide." Professor Casewell's team are already looking for viable treatments that effectively block the venom CTx. Having treatments available against both toxins has the potential to enhance the potency of varespladib, and could significantly reduce the long-term morbidity associated with spitting cobra bites in Africa and beyond.