tbuckley/cabot-search huggingface dataset:
STING: a master regulator in the cancer-immunity cycle
Authors: Yuanyuan Zhu, Xiang An, Xiao Zhang, Yu Qiao, Tongsen Zheng, Xiaobo Li
Journal: Molecular Cancer (2019)

The aberrant appearance of DNA in the cytoplasm triggers the activation of cGAS-cGAMP-STING signaling and induces the production of type I interferons, which play critical roles in activating both innate and adaptive immune responses. Recently, numerous studies have shown that the activation of STING and the stimulation of type I IFN production are critical for the anticancer immune response. However, emerging evidence suggests that STING also regulates anticancer immunity in a type I IFN-independent manner. For instance, STING has been shown to induce cell death and facilitate the release of cancer cell antigens. Moreover, STING activation has been demonstrated to enhance cancer antigen presentation, contribute to the priming and activation of T cells, facilitate the trafficking and infiltration of T cells into tumors and promote the recognition and killing of cancer cells by T cells. In this review, we focus on STING and the cancer immune response, with particular attention to the roles of STING activation in the cancer-immunity cycle. Additionally, the negative effects of STING activation on the cancer immune response and non-immune roles of STING in cancer have also been discussed.
Treatment with Novel Agents in Patients with Multiple Myeloma in México: Data of Characteristics, Treatment Patterns and Outcomes from a Health Care System
Authors: Fernando Pérez-Jacobo, Elia Zamora P., Irma Leticia Barrios-Hernández, Nubia Paloma Pérez-Mar, Lidia Mondragón-Posadas, Patricia Galindo-Delgado, Magdalena Bahena-García, Adrian Hernández-López
Journal: Blood (2019)
Health Literacy, Self-Efficacy and Knowledge of Sickle Cell Disease Among Caregivers
Authors: Maite E. Houwing, Rowena Grohssteiner, Sonja A.M.C. Teuben, Jan A Hazelzet, Anne P.J. de Pagter, Mirjam P. Fransen, Marjon H. Cnossen
Journal: Blood (2019)
A Circular RNA Molecule, circRAB11FIP1, Is Associated with TP53 Mutations and Is of Potential Prognostic and Functional Significance in Mantle Cell Lymphoma: Data from the Nordic MCL2 and MCL3 Studies
Authors: Mette Dahl, Simon Husby, Christian Winther Eskelund, Christophe Côme, Sara Ek, Arne Kolstad, Riikka Räty, Mats Jerkeman, Christian H. Geisler, Lasse Sommer Kristensen, Kirsten Grønbæk
Journal: Blood (2019)
Preliminary Minimal Residual Disease Analysis of the Australasian Leukaemia &amp; Lymphoma Group (ALLG) ALL8 Study of Front-Line Blinatumomab with Chemotherapy in Adults with Ph Negative B-Cell Acute Lymphoblastic Leukaemia
Authors: Shaun Fleming, Nicola Venn, John Reynolds, Uyen Nguyen, John Kwan, John Moore, David T Yeung, Michael F. Leahy, Matthew Greenwood, Emma Verner, Ashish Bajel, Leanne Berkahn, Andrew H. Wei, Rosemary Sutton
Journal: Blood (2019)
RARE-48. GROWING KNOWLEDGE AND EMERGING QUESTIONS RELATED TO POT-1 GERMLINE MUTATIONS AND ASSOCIATED MALIGNANCIES: A CASE REPORT
Authors: Amber Ruiz, Boryana Eastman, Lia Halasz, Gail Jarvik, Lauren Brown, Jerome Graber
Journal: Neuro-Oncology (2019)

Abstract Protection of telomeres 1 (POT1) is a member of a family of genes responsible for maintenance of telomere integrity. Germline mutations of the POT1 gene have been associated with tumorigenesis of multiple tissue types, conferring an increased risk of development of malignancies such as melanoma, chronic lymphocytic leukemia, gliomas, and cardiac sarcomas. We present the case of a 28 year old male who first presented at the age of 15 with personality changes. Several years later, he was found to have a left frontal, IDH mutated, WHO grade III anaplastic astrocytoma. Following successful treatment with gross total resection, radiation therapy, and adjuvant chemotherapy, the patient represented with an MRI showing enhancement concerning for osteomyelitis and possible tumor recurrence. Pathology of the dura was consistent with myxofibrosarcoma. Staging PET scan at that time revealed multiple hypermetabolic lung lesions found to be Lanagerhans cell histiocytosis. Given the patient’s complex oncological history, genetic testing was performed. He was found to carry a heterozygous mutation of the POT1 gene. This case raises the suspicion for a broader POT1-associated cancer predisposition than previously described in the literature. Moreover, this prompts further questioning of an association between POT1 mutations and IDH status in related gliomas. Patients with POT1 mutations might also be at increased risk of secondary malignancies after radiation exposure, which may require closer observation after treatment.
Mutational Patterns and Clonal Architecture of Therapy-Related Acute Myeloid Leukemia
Authors: Hassan Awada, Teodora Kuzmanovic, Ashwin Kishtagari, Jibran Durrani, Arda Durmaz, Sanghee Hong, Cassandra M Kerr, Vera Adema, Yihong Guan, Sonia Sandhu, Aziz Nazha, Manja Meggendorfer, Torsten Haferlach, Hetty E. Carraway, Mikkael A. Sekeres, Valeria Visconte, Jaroslaw P. Maciejewski
Journal: Blood (2019)
First Clinical Study of the B-Cell Maturation Antigen (BCMA) 2+1 T Cell Engager (TCE) CC-93269 in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM): Interim Results of a Phase 1 Multicenter Trial
Authors: Luciano J. Costa, Sandy W. Wong, Arancha Bermúdez, Javier de la Rubia, María-Victoria Mateos, Enrique M. Ocio, Paula Rodríguez-Otero, Jesús San-Miguel, Shaoyi Li, Rafael Sarmiento, Pilar Lardelli, Allison Gaudy, Isaac Boss, Lisa M. Kelly, Michael R. Burgess, Kristen Hege, William I. Bensinger
Journal: Blood (2019)
Ampicillin for Typhoid Carriers
Authors: A. B. Christie
Journal: BMJ (1964)

CJOUnNc L tion necessary.The one case had taken only small oral doses of ergotamine; the other was receiving subcutaneous dihydroergotamine.This report was referred to in our article' in the British Medical 7ournal four years ago.Our own report was on gangrenous ergotism in a woman of 45 who had taken only 7 tablets, each containing 1 mg.ergotamine tartrate, over three days-not for migraine.Amputation of both legs, the right thumb, and tip of right index finger had to be performed.We believe that migraine confers immunity to possible side-effects from ergotamine, and further that the route of administration is probably of little importance.In some cases side-effects may arise because of abnormal response to accepted therapeutic dosage.The smallest possible dose that will control the symptoms of migraine must be found by gradually increasing the dose with each attack-increasing from 1 mg.by 1 mg.increments, respectively, in subsequent attacks until either a satisfactory dose is thus safely found, or side-effects are too severe.Paraesthesiae, coldness, and pains in the extremities should be reported at once.-We are, etc.,
Ruxolitinib Is an Effective Salvage Treatment for Multidrug-Resistant Graft-Versus-Host Disease after Allogeneic Hematopoietic Transplantation
Authors: Sining Liu, Jiaoyu Zhao, Lanping Xu, Xiaohui Zhang, Yu Wang, Yuhong Chen, Kaiyan Liu, Xiaojun Huang, Xiaodong Mo
Journal: Blood (2019)
PATH-23. PROGNOSTIC AND RADIOGRAPHIC CORRELATES OF A PROSPECTIVELY COLLECTED MOLECULARLY PROFILED COHORT OF IDH-WILDTYPE ASTROCYTOMAS
Authors: Andrew Lin, Tejus Bale, Ingo Mellinghoff, Viviane Tabar, Lauren Schaff, T Jonathan Yang, Robert Young, Barry Taylor, Marc Rosenblum, Philip Jonsson
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND In the molecular era, the relevance of tumor grade for prognostication of IDH-wildtype (WT) astrocytomas has been debated. It has been suggested that lower-grade gliomas with molecular features of glioblastoma, IDH-WT have a similar prognosis to glioblastoma and should be considered for the same clinical trials. METHODS We integrated prospective clinical sequencing via the FDA-approved genomic sequencing assay MSK-IMPACT from 564 patients with IDH-WT astrocytomas (26 grade II, 71 grade III, and 467 grade IV) with clinical data. RESULTS Compared to grade III IDH-WT astrocytomas, grade II tumors harbor fewer chromosome 7/10 alterations and EGFR amplifications (p=0.07 and 0.03), but the same frequency of TERT promoter mutation. In contrast, there is no difference in the frequency of these canonical molecular features in grade III versus grade IV IDH-WT disease. Additionally, grade II astrocytomas harbor fewer cell cycle-pathway alterations than grade III tumors (p=6.9e-7). Progression-free (PFS) and overall survival (OS) for grade II astrocytomas were significantly longer than grade III tumors (p=0.02 and p=0.008, respectively), whereas there was no difference in PFS and OS for grade III compared to grade IV tumors. Median PFS for grade II vs. III vs. IV: 19 mo vs. 11 mo vs. 9 mo; median OS: 44 mo vs. 23 mo vs. 23 mo. In lower-grade IDH-WT astrocytomas, gliomatosis is associated with grade II histology (p=0.04), the absence of cell-cycle alterations (p=0.008), and more alterations in the PI3K-AKT pathway (p=0.09). CONCLUSION Histologic grade has genotypic and phenotypic associations, remains prognostically important in IDH-WT astrocytomas, and should be considered when enrolling patients to clinical trials.
Reevaluating the Role of Cytogenetic Testing in Patients with Suspected Myelodysplastic Syndrome in the Era of Next Generation Sequencing
Authors: Eri Kawata, Anargyros Xenocostas, Cyrus C. Hsia, Alejandro Lazo-Langner, Kang Howson-Jan, Uday Deotare, Lalit Saini, Benjamin Hedley, Ping Yang, Michael Levy, Hanxin Lin, Bekim Sadikovic, Ian Chin-Yee
Journal: Blood (2019)
Abstract 19722: Exome Sequencing Identifies a ZBTB17 Truncation Variant in Arrhythmogenic Cardiomyopathy
Authors: Sunny C Chang, Hane Lee, Martin Cadeiras, Aldons J Lusis, Stanley Nelson, Jessica J Wang
Journal: Circulation (2017)

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder of the myocardium characterized by progressive fibrofatty replacement that predisposes to sudden death. Al...
EXTH-48. GALECTIN-1 INHIBITION SENSITIZES RADIATION TREATMENT IN A PRE-CLINICAL MODEL OF GLIOBLASTOMA
Authors: Fraser Henderson, Arabinda Das, Indira Kanginakudru, Daniel G McDonald, Libby Kosnik Infinger, William Vandergrift III, Abhay Varma, Kenneth N Vanek, Scott Lindhorst, Sunil Patel, David Cachia
Journal: Neuro-Oncology (2019)

Abstract Radioresistance remains a major clinical challenge in glioblastoma (GB) therapy. However, the mechanism for the development of radioresistance in GB is unclear. Mounting evidence suggests that Galectin-1 (Gal1: a carbohydrate-binding protein galectin-1) contributes to the radioresistance of GB tumors. Recently, several Gal1-targeting compounds have emerged. OTX008 is a calixarene derivative designed to bind the Gal1 amphipathic β-sheet conformation. Our study aimed to reduce galectin-1 expression using OTX008 in a human GB pre-clinical model. For these studies an in vivo GL261 murine models of GB were utilized to assess efficacy of treatment with radiation plus OTX008. Our results demonstrated that inhibition of Gal-1 with OTX008 plus radiation showed significantly decrease in GB growth rate and improved survival in in vivo. OTX008 treatment plus radiation was associated with downregulation of Gal1 and Ki67 in treated tumors, as well as decreased microvessel density and VEGFR2 expression. Finally, combination studies showed OTX008 synergy with radiation therapies, principally when OTX008 was administered first. This study provides insights of Gal-1inhibitory effects of OTX008 and its enhancement of the efficacy of radiotherapy in mouse models of GB suggest that further studies are warranted.
The Transmembrane Receptor Roundabout 1 (ROBO1) Is Necessary for Multiple Myeloma Proliferation and Homing to the Bone Marrow Niche
Authors: Giada Bianchi, Peter G. Czarnecki, Matthew Ho, Aldo M. Roccaro, Antonio Sacco, Yawara Kawano, Anil Aktas Samur, Annamaria Gulla, Tianzeng Chen, Kenneth Wen, Xinchen Wu, Yu-Tzu Tai, Gulden Camci-Unal, Irene M. Ghobrial, Ruben D. Carrasco, Kenneth C. Anderson
Journal: Blood (2019)
A Phase II Study of Daratumumab in Patients with High-Risk MGUS and Low-Risk Smoldering Multiple Myeloma: First Report of Efficacy and Safety
Authors: Omar Nadeem, Robert Redd, Laura V. Stampleman, Jeffrey V. Matous, Andrew J. Yee, Jeffrey A. Zonder, Andrew Kin, Jacalyn Rosenblatt, Mark Bustoros, MD, Julia Prescott, Alexandra Savell, Kathleen Guimond, Erin Frey, Rachel Styles, Adrienne Bielawski, Cody J Boehner, Nang Kham Su, Multiple Myeloma Research Foundation Multiple Myeloma Research Foundation, The Leukemia & Lymphoma Society The Leukemia & Lymphoma Society, BCRP Blood Cancer Research Partnership, Adam S Sperling, Giada Bianchi, Jacob P. Laubach, Jorge J. Castillo, Nikhil C. Munshi, Kenneth C. Anderson, Paul G. Richardson, Lorenzo Trippa, Irene M. Ghobrial
Journal: Blood (2019)
Galectin-1 Is Highly Expressed By Myeloma Cells and the Bone Marrow Microenvironment and Its Suppression Delineates a New Therapeutic in Vitro and in Vivo Strategy in Multiple Myeloma
Authors: Paola Storti, Gaetano Donofrio, Valentina Marchica, Daniela Guasco, Katia Todoerti, Irma Airoldi, Judith Anderson, Marina Bolzoni, Valentina Ferri, Eugenia Martella, Cristina Mancini, Nicoletta Campanini, Antonino Neri, G. David Roodman, Franco Aversa, Nicola Giuliani
Journal: Blood (2014)
TMIC-54. COMPARISON OF CELLULAR FEATURES AT AUTOPSY IN GLIOBLASTOMA PATIENTS WITH STANDARD TREATMENT OF CARE AND TUMOR TREATMENT FIELDS
Authors: Allison Lowman, Alexander Barrington, Elizabeth Cochran, Jennifer Connelly, Wade Mueller, Peter LaViolette
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The FDA has approved the use of tumor treatment fields (TTFields) on patients with recurrent glioblastoma (GBM). A recent clinical trial showed that the use of TTFields along with standard treatment of care resulted in increased quality of life and survival over five years. TTFields work by delivering low intensity electric fields that disrupt GBM tumor cell division. This works to slow or even stop GBM tumor cells from dividing. METHODS Brain tissue samples were taken from thirteen GBM patients, diagnosed at autopsy. Three patients underwent standard clinical treatment and ten patients underwent TTField therapy in addition to the standard. Tissue samples were acquired from regions where enhancement was seen on the last clinical T1 plus contrast MRI prior to death. Samples were paraffin embedded and stained with hematoxylin and eosin (H&amp;E) and Ki67. The slides were digitized, allowing analysis of the cellular features. RESULTS Using the H&amp;E stained slides we compared cellular density between both groups. We found that there was not a noticeable difference in the nuclei density in areas of tumor between the groups. The percent of positive nuclei on the Ki67 stained slides was calculated and there was increased mitotically active cells per area of tissue in patients that did not undergo TTField therapy. CONCLUSION These findings suggest there is a difference in the cellular features in areas of tumor in patients treated with TTFields compared to those with standard treatment alone. Additional research needs to be done evaluating more patients.
Preclinical Development of an Anti-CD38 Antibody-Drug Conjugate for Treatment of Hematological Malignancies
Authors: Lingna Li, Wenyong Tong, Megan Lau, Katherine Fells, Tong Zhu, Yingqing Sun, Ernest Kovacs, Alisher Khasanov, Zheng Yan, Dalun Deng, Ken Takeshita, Gunnar F. Kaufmann, Henry Ji, Hui Li, Hong Zhang
Journal: Blood (2019)
Third-Party BK Virus Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation
Authors: Amanda L. Olson, Ruitao Lin, Mustafa Bdaiwi, Peter F Thall, Hind Rafei, Indreshpal Kaur, Li Li, Glorette Abueg, Melissa Timmons, Roy Chemaly, David Marin, Amin M. Alousi, Sairah Ahmed, Stefan O. Ciurea, Chitra Hosing, Partow Kebriaei, Roy B Jones, Borje S Andersson, Betul Oran, Ala Abuddayeh, Uday Popat, Richard E. Champlin, Elizabeth J. Shpall, Katayoun Rezvani
Journal: Blood (2019)
The Relationship between Baseline Biomarkers and Efficacy of Isatuximab in Combination with Pomalidomide and Dexamethasone in RRMM: Insights from Phase 1 and Phase 3 Studies
Authors: Paul G. Richardson, Joseph Mikhael, Thierry Facon, William I. Bensinger, Sandrine Macé, Marielle Chiron, Helgi van de Velde, Frank Campana, Li Liu, Michel Attal
Journal: Blood (2019)
RTHP-24. TRENDS IN THE UP FRONT USE OF STEREOTACTIC RADIOSURGERY FOR GLIOBLASTOMA
Authors: Rodney Wegner, Stephen Abel, Tulika Ranjan, Richard Williamson, Alexander Yu, Linda Xu, Stephen Karlovits
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND GBM is typically managed with a combined modality approach including resection followed by adjuvant chemoradiation. Despite aggressive up front treatment local failure occurs in the vast majority of patients. The concept of dose escalation through use of stereotactic radiosurgery (SRS) was tested in RTOG 9305 in the pre-temozolomide era with the hopes of improving control, ultimately showing no benefit. We used the National Cancer Database (NCDB) to examine trends in the use of up-front SRS, to see if it had truly fallen out of favor, and if it had any impact on outcome. METHODS We queried the NCDB from 2004–14 for GBM patients that had radiation and 2 months of follow up. Odds ratios were used to determine predictors of SRS. Univariable and multivariable Cox regressions were used to determine potential predictors of overall survival (OS). Propensity adjusted multivariable analysis was used to account for any indication bias. RESULTS We identified 62,681 patients meeting eligibility criteria, of which 1,046 had SRS. SRS decreased over time from 3% to less than 1%. Predictors of SRS were increased age, government insurance, lower comorbid score, treatment at an academic facility, metropolitan location, increased distance to facility, smaller tumor, lack of surgery, no chemotherapy, and more remote year of treatment. Median overall survival was 13.1 months in the non-SRS group and 12.9 months in the SRS group, p=0.28. On multivariable analysis increased age, lack of chemotherapy, higher comorbidity score, extent of surgery, non-academic facility, decreased education, government insurance, urban location, Caucasian race, male gender, larger tumor, and more remote year of treatment predicted for worse overall survival. CONCLUSIONS Use of up-front SRS in the management of GBM has decreased over time, in concordance with past randomized trials examining its use. Our analysis did not show any benefit in survival with its use.
TMIC-20. ELIMINATION OF SENESCENT ASTROCYTES IN THE BRAIN TUMOR MICROENVIRONMENT ATTENUATES GLIOBLASTOMA RECURRENCE AFTER RADIOTHERAPY
Authors: Eliot Fletcher-Sananikone, Bipasha Mukherjee, Sandeep Burma
Journal: Neuro-Oncology (2019)

Abstract Glioblastomas (GBM) are treated with high doses of ionizing radiation (IR) yet these tumors inevitably recur, and the recurrent tumors are highly therapy resistant. During GBM therapy, the surrounding brain tissue is irradiated along with the tumor. IR induces senescence in multiple cell types, and senescent stromal cells are known to promote the growth of neighboring tumor cells by secreting cytokines which create a senescence-associated secretory phenotype (SASP). We hypothesize that IR-induced senescence of normal brain cells in the tumor microenvironment is a powerful driver of GBM recurrence. We intra-cranially irradiated C57BL/6J mice, and found evidence of widespread senescence, with the astrocytic population being highly susceptible. Genomic analyses of irradiated brains revealed an altered transcriptomic profile which included upregulation of CDKN1A (p21), a key enforcer of senescence, and increased expression of SASP proteins including HGF, the ligand for the RTK Met. We orthotopically implanted mock-irradiated or irradiated mice with a limiting number of syngeneic glioma cells. Pre-irradiation of mouse brains resulted in a striking increase in tumor growth and invasion driven by Met activation in the tumor cells. Importantly, irradiated p21-/- mouse brains did not exhibit SASP and failed to promote tumor growth. Irradiated primary astrocytes underwent senescence in vitro and promoted the migration of glioma cells, and this could be attenuated with HGF-neutralizing antibodies or by the Met inhibitor Crizotinib. These findings indicate that SASP factors (like HGF) in the irradiated brain microenvironment could drive GBM recurrence after radiotherapy via the activation of RTKs (like MET) in the tumor cells. Significantly, we found that senolytic drugs can selectively kill senescent astrocytes both in vitro and in vivo resulting in attenuated growth of glioma cells. These results are of great translational significance as they indicate that adjuvant therapy with senolytic drugs might attenuate GBM recurrence after radiotherapy.
Cooperativity between Flt3/Syk and Proteasome Inhibitors in Flt3mutant/Wildtype AML, By Acting on the Oxphos and Wnt Endpoints of Syk and p62SQSTM1 Pathways Prohibits Protective Autophagy; While Downregulation of NRF2, NQO1, Jun, and b-Catenin Bypasses Interfering RAS or WT1 Co-Mutations
Authors: Sravanti Rangaraju, Silvia Marino, G. David Roodman, Larry D. Cripe, Baskar Ramdas, Lakshmi Reddy Palam, Katie J Sargent, Hamid Sayar, Heiko Konig, Reuben Kapur, H. Scott Boswell
Journal: Blood (2019)
Targeted Delivery of Nanocarrier-Conjugated Doxorubicin to Widen the Therapeutic Window of the Most Active Drug in Lymphoma Therapeutics
Authors: Artavazd Arumov, Piumi Y. Liyanage, Asaad Trabolsi, Lingxiao Li, Evan R. Roberts, Daniel Bilbao, Roger M. LeBlanc, Jonathan H. Schatz
Journal: Blood (2019)
The Optimal Treatment Strategy for Adult Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in First Complete Remission in the Era of High-Intensity Chemotherapy
Authors: Shinichi Kako, Fumihiko Hayakawa, Kiyotoshi Imai, Junji Tanaka, Shuichi Mizuta, Satoshi Nishiwaki, Heiwa Kanamori, Noriko Doki, Naoyuki Uchida, Kazuhiro Ikegame, Takahiro Fukuda, Tatsuo Ichinohe, Shuichi Ota, Yoshinori Tanaka, Tohru Murayama, Shingo Kurahashi, Toru Sakura, Noriko Usui, Shigeki Ohtake, Hitoshi Kiyoi, Itaru Matsumura, Yasushi Miyazaki, Yoshiko Atsuta
Journal: Blood (2019)
Treatment of Refractory Acute Myeloid Leukemia and High-Grade Myelodysplastic Syndrome: Implications of Further Care at an Academic Center Versus Community Setting
Authors: Noam E. Kopmar, Megan Othus, Kelda Gardner, Carole M. Shaw, Anna B. Halpern, Bart L. Scott, Paul C. Hendrie, Roland B. Walter, Pamela S. Becker, Elihu H. Estey, Mary-Elizabeth M. Percival
Journal: Blood (2019)
Practical aspects of childhood epilepsy
Authors: Maria-Christina Petropoulos, Karen Bonaiuto, Janet Currier, Deb K Pal,
Journal: BMJ (2019)

### What you need to know 

Children and adolescents with epilepsy are medically managed by paediatricians with expertise in the condition, but non-specialist doctors can also help these young people live a fuller life. In this update we focus on important issues that are sometimes misunderstood, particularly those with little published guidance or where new evidence or guidance has emerged. The advice applies mainly to children with common epilepsies attending mainstream schools. Children with complex epilepsy require specialist guidance.

Official guidance and discussions on social media are conservative on the question of switching1 between different products, while prescribers are encouraged to use cheaper generic drug treatments. On balance, we advise consistency in prescribing (in the UK it not uncommon for the pharmacy to have different formulations every time the patient goes to renew the prescription) because comparative bioavailability data are incomplete for every anti-epileptic drug.2 Only the 2016 EQUIGEN study3 showed that switching between branded and generic lamotrigine was safe. Furthermore, the different names, packaging, and appearance of alternative products may cause confusion, anxiety, or occasionally non-adherence when prescriptions are refilled.

Table 1 lists anti-epileptic drugs stratified by risk of switching, according to their therapeutic index and release characteristics.4

View this table:

Table 1 
Risk categories for switching between generic and branded formulations of anti-epileptic drugs4



Management of a missed …