Article
Neurosciences
Yachin Chen, Nicholas Fallon, Barbara A. K. Kreilkamp, Christine Denby, Martyn Bracewell, Kumar Das, Emily Pegg, Rajiv Mohanraj, Anthony G. Marson, Simon S. Keller
Summary: This study found significant volume reduction of the left and right anterior thalamic nuclei only in patients with refractory idiopathic generalised epilepsy (IGE), compared to those with non-refractory IGE. Both refractory and non-refractory IGE patients showed significant alterations of functional connectivity between the centromedian nucleus and cortex, with only refractory patients showing altered cortical connectivity with the ventral lateral nuclear group. Refractory IGE patients had increased functional connectivity between the left and right ventral lateral posterior nuclei and cortical regions compared to non-refractory IGE patients, mainly in the frontal lobe.
HUMAN BRAIN MAPPING
(2021)
Article
Health Care Sciences & Services
Grace S. Shieh
Summary: This article reviews the applications of the synthetic lethal (SL) concept in translational cancer medicine over the past five years. It discusses the use of SL concept in drug combinations to overcome tumor resistance, the identification of prognostic and predictive biomarkers using synthetic lethality, the application of SL interactions in stratifying patients for targeted and immunotherapy, as well as the challenges and future directions in this field.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Medicine, General & Internal
Sandra Elena-Perez, David Hansoe Heredero-Jung, Asuncion Garcia-Sanchez, Miguel Estravis, Maria J. Martin, Jacinto Ramos-Gonzalez, Juan Carlos Trivino, Maria Isidoro-Garcia, Catalina Sanz, Ignacio Davila
Summary: The study revealed that IL5RA is overexpressed in patients with asthma, with significant expression differences in different asthmatic types. It also found that some asthmatic patients respond efficiently to benralizumab treatment. These results provide insights for achieving more personalized asthma management.
FRONTIERS IN MEDICINE
(2021)
Review
Health Care Sciences & Services
Francesca Cianci, Ivan Verduci
Summary: The loss of function and aberrant expression of ion channels and transporters, particularly the CLIC1 protein, play a crucial role in the development of diseases such as cancer and neurodegenerative diseases.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Katja Goricar, Vita Dolzan, Metka Lenassi
Summary: EVs have emerged as a potential source of biomarkers in liquid biopsy, offering valuable insights for personalized cancer treatment in oncology.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Gastroenterology & Hepatology
Stephen L. Chan, Nathalie Wong, W. K. Jacky Lam, Ming Kuang
Summary: Advances in systemic treatment for hepatocellular carcinoma (HCC) have introduced more options but personalized treatment approaches are crucial due to differing patient responses. Biomarker data and tumor heterogeneity analysis have proven to be effective methods in guiding treatment decisions for HCC patients.
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Health Care Sciences & Services
Yuichi Yamamoto, Norihiro Kanayama, Yusuke Nakayama, Nobuko Matsushima
Summary: In recent years, personalized medicine has made significant progress in the fields of cancer and rare diseases. However, there is still a need for further research and development in other disease areas such as rheumatoid arthritis, psoriasis, and Alzheimer's disease. These diseases have high unmet needs for personalized medicine, including understanding disease mechanisms, developing diagnostic methods, and finding new therapeutic drugs.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Clinical Neurology
Hyo Min Lee, Fatemeh Fadaie, Ravnoor Gill, Benoit Caldairou, Viviane Sziklas, Joelle Crane, Seok-Jun Hong, Boris C. Bernhardt, Andrea Bernasconi, Neda Bernasconi
Summary: In this study, the authors used unsupervised machine learning to analyze structural MRI data in epilepsy patients. They identified four latent disease factors that were predictive of drug response, surgical outcome, and cognitive dysfunction. This data-driven analysis provides insights into the interindividual variability of the disease and could potentially improve clinical prognostics.
Review
Clinical Neurology
Emilio Perucca, Piero Perucca, H. Steve White, Elaine C. Wirrell
Summary: Drug resistance affects about a third of people with epilepsy, and its prevalence varies depending on the epilepsy syndrome, cause, age of seizure onset, and neurological deficits. After two failed attempts with antiseizure medications, individuals should be referred to a comprehensive epilepsy centre for re-evaluation and targeted management. Delay in finding an effective treatment can negatively impact outcome and increase the risk of cognitive disability, comorbidities, and premature mortality.
Review
Neurosciences
Iman Imtiyaz Ahmed Juvale, Ahmad Tarmizi Che Has
Summary: Epilepsy is a common neurological disorder with a high incidence rate, often accompanied by comorbid conditions that impact patients' quality of life. Current treatment options include anti-epileptic drugs, surgery, and ketogenic diet, but drug resistance is a major concern. Understanding the underlying mechanisms of pharmacoresistant epilepsy is crucial for developing more effective treatments. Various theories have been proposed, such as the gene variant hypothesis, network hypothesis, multidrug transporter hypothesis, and target hypothesis, with potential interconnections between their mechanisms for novel therapy development.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Review
Health Care Sciences & Services
Joanna Kozlowska-Maslon, Kacper Guglas, Anna Paszkowska, Tomasz Kolenda, Marta Podralska, Anna Teresiak, Renata Blizniak, Katarzyna Lamperska
Summary: Long non-coding RNAs (lncRNAs) play crucial regulatory roles in both normal and cancer cells, and are associated with tumorigenesis, treatment response, and patient outcomes. This review examines the role of lncRNAs in radiotherapy and their impact on treatment efficacy.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Medicine, Research & Experimental
Celia Castano-Amores, Xando Diaz-Villamarin, Ana Maria Perez-Gutierrez, Alba Antunez-Rodriguez, Ana Pozo-Agundo, Eduardo Moreno-Escobar, Jesus Gabriel Sanchez-Ramos, Luis Javier Martinez-Gonzalez, Cristina Lucia Davila-Fajardo
Summary: Beta-blockers are commonly used to treat cardiovascular diseases, but genetic differences may affect individual responses. The ADRB1 Arg389Gly variant is the most studied genetic polymorphism in relation to bisoprolol response, but results have been inconclusive. Further studies are needed to explore the impact of genetic variants on bisoprolol response.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Biochemistry & Molecular Biology
Krzysztof Lukawski, Stanislaw J. Czuczwar
Summary: Approximately 70% of epilepsy patients can be successfully treated with antiepileptic drugs, but drug-resistant epilepsy is associated with poor quality of life and increased morbidity and mortality. Various hypotheses have been proposed to explain pharmacoresistance, and the search for newer AEDs or non-AEDs may provide efficacious drugs. Combinations of AEDs exerting synergy in preclinical and clinical studies could be important in managing drug-resistant epilepsy.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Susan Morand, Monika Devanaboyina, Hannah Staats, Laura Stanbery, John Nemunaitis
Summary: Response to immunotherapy in ovarian cancer is limited, but stratification by tumor biomarkers may improve predictiveness. Future directions include utilizing these biomarkers to select ideal candidates, increasing the likelihood of success with immunotherapy in ovarian cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Veterinary Sciences
Heidrun Potschka, Andrea Fischer, Wolfgang Loescher, Holger A. Volk
Summary: Drug resistance is a major issue in the treatment of canine epilepsies, affecting quality of life and survival. Human medicine research has shown that disease severity and pharmacokinetic changes contribute to antiseizure medication failure. In dogs, there is limited understanding of clinical patterns and mechanisms of drug-resistant epilepsy, but factors such as seizure density, genetic background, and epigenetic mechanisms may influence medication efficacy.
VETERINARY JOURNAL
(2023)
Review
Pharmacology & Pharmacy
Hani Essa, Rajiv Sankaranarayanan, Lauren Walker
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Lauren E. Walker, Richard FitzGerald, Geoffrey Saunders, Rebecca Lyon, Michael Fisher, Karen Martin, Izabela Eberhart, Christie Woods, Sean Ewings, Colin Hale, Rajith K. R. Rajoli, Laura Else, Sujan Dilly-Penchala, Alieu Amara, David G. Lalloo, Michael Jacobs, Henry Pertinez, Parys Hatchard, Robert Waugh, Megan Lawrence, Lucy Johnson, Keira Fines, Helen Reynolds, Timothy Rowland, Rebecca Crook, Emmanuel Okenyi, Kelly Byrne, Pavel Mozgunov, Thomas Jaki, Saye Khoo, Andrew Owen, Gareth Griffiths, Thomas E. Fletcher
Summary: Repurposing the drug nitazoxanide may provide effective antiviral concentrations in COVID-19 patients, with the medication showing good safety and tolerability in healthy adult participants. This has led to the initiation of a phase Ib/IIa study in patients with COVID-19.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Letter
Pediatrics
James G. Moss, Daniel Young, Asia N. Rashed, Lauren E. Walker, Daniel B. Hawcutt
ARCHIVES OF DISEASE IN CHILDHOOD
(2023)
Article
Pharmacology & Pharmacy
Roseann S. Gammal, Munir Pirmohamed, Andrew A. Somogyi, Sarah A. Morris, Christine M. Formea, Amanda L. Elchynski, Kazeem A. Oshikoya, Howard L. McLeod, Cyrine E. Haidar, Michelle Whirl-Carrillo, Teri E. Klein, Kelly E. Caudle, Mary Relling
Summary: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with the development of acute hemolytic anemia in the presence of oxidative stress. This guideline provides information on using G6PD genotype for diagnosing G6PD deficiency and categorizes medications based on their risk level in individuals with G6PD deficiency. High-risk medications should be avoided, medium-risk medications should be used with caution, and low-risk medications can be used without considering the G6PD phenotype.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Pharmacology & Pharmacy
Muhammed Shiraz Moosa, Giusy Russomanno, Jeffrey R. Dorfman, Hannah Gunter, Chandni Patel, Eithne Costello, Dan Carr, Gary Maartens, Munir Pirmohamed, Christopher Goldring, Karen Cohen
Summary: This study investigated the concentrations of miR-122 in participants with antituberculosis drug-induced liver injury (AT-DILI) and its correlation with alanine aminotransferase (ALT) concentrations. The study found that miR-122 concentrations in AT-DILI patients were significantly higher than those in healthy volunteers and in patients on antituberculosis therapy without liver injury, and N-acetylcysteine (NAC) had no effect on miR-122 concentrations.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Tjeerd Pieter van Staa, Munir Pirmohamed, Anita Sharma, Iain Buchan, Darren M. Ashcroft
Summary: This study evaluated drug-drug interactions (DDIs) between antibiotics and nonantibiotic drugs listed with warnings of severe outcomes in the British National Formulary. The results showed no substantial risk of DDIs despite the warnings in the national formulary.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Genetics & Heredity
Munir Pirmohamed
Summary: In this Review, the current state of the pharmacogenomics field is discussed, along with clinically relevant drug-gene associations and the steps required for implementing pharmacogenomics into clinical practice. The role of pharmacogenomics in drug discovery and development is also considered. The variability in drug response between individuals, which can be attributed to genomic factors, is a global concern. Despite the availability and decreasing cost of genotyping technologies, challenges in implementing pharmacogenomics lie in adapting current clinical pathways and addressing the knowledge gap in healthcare professionals. Furthermore, pharmacogenomics shows promise in enhancing drug discovery and development outcomes.
NATURE REVIEWS GENETICS
(2023)
Article
Public, Environmental & Occupational Health
Elpida Kontsioti, Simon Maskell, Munir Pirmohamed
Summary: This study aimed to evaluate the impact of multiple design criteria for reference sets used to assess the performance of signal detection algorithms for drug-drug interactions. Custom-made reference sets of different sizes were generated based on various design criteria. The performance metrics of three algorithms were assessed using FDA Adverse Event Reporting System data, and the results showed that the composition of reference sets significantly impacted the evaluation metrics.
PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
(2023)
Review
Clinical Neurology
Corey Ratcliffe, Guleed Adan, Anthony Marson, Tom Solomon, Jitender Saini, Sanjib Sinha, Simon S. Keller
Summary: Neurocysticercosis (NCC), a parasitic CNS infection, is the leading global cause of acquired epilepsy but remains understudied. The factors contributing to recurrent seizures and the features predisposing to an epileptogenic state in NCC are uncertain.
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
(2023)
Review
Geriatrics & Gerontology
Eve Braithwaite, Oliver M. Todd, Abigail Atkin, Rachel Hulatt, Ragy Tadrous, David P. Alldred, Munir Pirmohamed, Lauren Walker, Rebecca Lawton, Andrew Clegg
Summary: A systematic review with meta-analysis was conducted to examine interventions aimed at reducing anticholinergic burden in older adults. The results showed no significant difference in outcomes between control and intervention group for falls, cognition, anticholinergic burden, or quality of life. Short follow-up time and lack of training and support surrounding successful deprescribing may have contributed to these results.
Article
Pharmacology & Pharmacy
Victoria Rollinson, Neil French, Richard Turner, Munir Pirmohamed
Summary: This study aimed to assess the current educational status of pharmacogenomics within the UK pharmacy profession and identify future educational and infrastructure needs of pharmacists. A survey was conducted among practicing pharmacists, preregistration pharmacists, and MPharm students. The findings indicate the need for further education and the development of PGx guidelines to prepare the pharmacy workforce for PGx implementation.
JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS
(2023)
Editorial Material
Clinical Neurology
Ulf Kallweit, Anthony G. Marson
Summary: The ninth Congress of the European Academy of Neurology focuses on the theme of "neurology beyond big data", aiming to explore the potential of neurological data to drive discoveries and enhance patient outcomes and brain health.
NATURE REVIEWS NEUROLOGY
(2023)
Article
Public, Environmental & Occupational Health
Tjeerd Pieter van Staa, Munir Pirmohamed, Anita Sharma, Darren M. M. Ashcroft, Iain Buchan
Summary: This study aims to assess the relationship between medication classes and adverse drug reactions (ADR) and emergency hospital admission. Through big data analysis, it was found that certain medication classes have a higher risk of ADR-related hospitalization. Therefore, there is a need for regular systematic assessment of the harm-benefit ratio of medicines.
PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
(2023)
Article
Multidisciplinary Sciences
Sylvia Hartmann, Summaira Yasmeen, Benjamin M. Jacobs, Spiros Denaxas, Munir Pirmohamed, Eric R. Gamazon, Mark J. Caulfield, Harry Hemingway, Maik Pietzner, Claudia Langenberg
Summary: The study identified three novel genomic regions related to Raynaud's phenomenon risk, prioritized candidate causal genes, and revealed a likely detrimental effect of low fasting glucose levels on RP risk. The research also highlighted opportunities for drug repurposing and provided robust evidence for a strong genetic contribution to RP.
NATURE COMMUNICATIONS
(2023)
Article
Gastroenterology & Hepatology
Brian Ho, Andrew Thompson, Andrea L. Jorgensen, Munir Pirmohamed
Summary: This study assessed the utility of the fatty liver index (FLI) for risk stratification of non-alcoholic fatty liver disease (NAFLD) and associated comorbidities. The results showed that FLI can effectively identify the risk of NAFLD and related comorbidities, including cardiovascular metabolic diseases and malignant tumors, and is closely associated with all-cause mortality risk.