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1. Development of antidrug antibodies against adalimumab maps to variation within the HLA-DR peptide-binding groove

Author

Teresa Tsakok, Jake Saklatvala, Theo Rispens, Floris C. Loeff, Annick de Vries, Michael H. Allen, Ines A. Barbosa, David Baudry, Tejus Dasandi, Michael Duckworth, Freya Meynell, Alice Russell, Anna Chapman, Sandy McBride, Kevin McKenna, Gayathri Perera, Helen Ramsay, Raakhee Ramesh, Kathleen Sands, Alexa Shipman, the Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) Study Group, A. David Burden, Christopher E.M. Griffiths, Nick J. Reynolds, Richard B. Warren, Satveer Mahil, Jonathan Barker, Nick Dand, Catherine Smith, and Michael A. Simpson

Subjects
Genetics, Therapeutics, Medicine
Abstract

Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6–36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.

Published
2023
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2. Caregiving in U.S. Gulf States During Natural Disasters and COVID-19

Author

Nathan A. Boucher DrPH, Kevin McKenna MPH, Carrie B. Dombeck MA, Amy G. Clark PhD, Ke Wang PhD, Jennifer M. Olsen DrPH, and Megan Shepherd-Banigan PhD

Subjects
Geriatrics, RC952-954.6
Abstract

Objectives: To ascertain common experiences and needs of a diverse group of caregivers challenged by hurricanes/floods and COVID-19. Methods: In-depth interviews with unpaid caregivers in U.S. Southeast/Gulf Coast states who had experienced caregiving during a natural disaster and during COVID-19. Results: Caregivers report challenges including daily living disruption, altered social supports, complicated health management, additional disaster planning, and emotional/financial impacts. Caregivers suggested helpful resources, policy options, and preparatory tools at individual, local, and health system levels to mediate discontinuity. Conclusions: Our data describe combined caregiver experiences of hurricanes/floods and the pandemic. Caregivers experience unique burdens related to care recipient diagnosis, location, and veteran status. Access to community supports varies as they manage the tasks required for care recipients’ health and safety. Our findings indicate the need for public health reinforcement of caregiving though caregiver pre-planning and targeted support. Bolstering understanding of communities’ caregiving capacity though first responder trainings and caregiver registries may enhance health and safety.

Published
2022
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3. Intermittent and Persistent Type 2 lupus: patient perspectives on two distinct patterns of Type 2 SLE symptoms

Author

David S Pisetsky, Rebecca E Sadun, Kai Sun, Amanda M Eudy, Megan E B Clowse, Lisa G Criscione-Schreiber, Mithu Maheswaranathan, Jennifer L Rogers, Jayanth Doss, Kevin McKenna, and Amy Corneli

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Objective We have developed a new conceptual model to characterise the signs and symptoms of SLE: the Type 1 and 2 SLE Model. Within the original model, Type 1 SLE consists of inflammatory manifestations like arthritis, nephritis and rashes; Type 2 SLE includes symptoms of fatigue, myalgia, mood disturbance and cognitive dysfunction. Through in-depth interviews, we explored how the Type 1 and 2 SLE Model fits within the lived experience of patients with SLE, with a focus on the connection between Type 1 and Type 2 SLE symptoms.Methods Semistructured in-depth interviews were conducted among adult participants meeting 1997 American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria for SLE. Participants were purposefully selected for age, race, sex and nephritis history. All interviews were audio-recorded and transcribed. Data were analysed through episode profile and thematic analysis.Results Through interviews with 42 patients with SLE, two patterns of Type 2 SLE emerged: Intermittent (n=18) and Persistent (n=24). Participants with Intermittent Type 2 SLE described feeling generally well when Type 1 is inactive; these participants were younger and had more internal SLE manifestations. Participants with Persistent Type 2 described always experiencing Type 2 symptoms despite inactive Type 1, although the severity may fluctuate. Participants with Persistent Type 2 SLE experienced traditional lupus symptoms of joint pain, hair loss and rash, but less often had severe organ system involvement.Conclusions By listening to the stories of our patients, we found two underlying patterns of Type 2 SLE: Intermittent Type 2 symptoms that resolve in synchrony with Type 1 inflammatory symptoms, and Persistent Type 2 symptoms that continue despite remission of Type 1 symptoms.

Published
2022
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4. Investigation of patient and observer agreement on description of seizures at initial clinical visit

Author

Maha N. Saleem, Christopher A. Arencibia, Kevin McKenna, Sabrina Cristofaro, Kamil Detyniecki, Daniel Friedman, Jacqueline French, Hal Blumenfeld, and the HEP Investigators

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract There have been few studies of agreement between seizure descriptions obtained from patients and observers. We investigated 220 patients and observers who completed structured questionnaires about patients’ semiological seizure features at the initial clinical visit. Inter‐rater reliability was assessed using Cohen’s kappa and indices of positive and negative agreement. Patients and observers had excellent agreement on the presence of memory impairment and generalized shaking and stiffness during seizures. In addition, patients under‐reported seizure descriptions more easily observed externally, whereas observers under‐reported change in patient location at seizure end. These findings may guide interpretation of clinical histories obtain in epilepsy care.

Published
2019
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5. Beyond the Individual: Social and Cultural Influences on the Health-Seeking Behaviors of African American Men

Author

Natalie T. Eley, Emily Namey, Kevin McKenna, Annette Carrington Johnson, and Greg Guest

Subjects
Medicine
Abstract

Morbidity and mortality rates are alarmingly high among African American men and are influenced by the health-seeking behaviors of this population. This study examined data from 40 focus groups with African American men in Durham, North Carolina, to better understand social and cultural influences on health-seeking behaviors. Data were analyzed using inductive thematic analysis. Three broad types of social/cultural influence on motivation to seek health care services were identified: family, culture and upbringing, and peers. Study findings confirm the importance of social relationships in influencing African American men’s health-seeking behaviors and offer characterization of the nature of influence across different types of relationships, according to the direct support or indirect messages they provide. Future programs can draw on these data to inform efforts to include family and peers as well as utilize existing cultural gender norms to the advantage of health promotion for African American men.

Published
2019
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6. Barriers to HIV testing in Guatemala: A Qualitative Study

Author

Lars Margolis, Narda Medina, Kimberly Gon, Brian Hagan, Kevin McKenna, Blanca Samayoa, Karla Patricia Alonzo Pacheco, Eduardo Arathoon, and Matthew Anderson

Subjects
Public aspects of medicine, RA1-1270, Sociology (General), HM401-1281
Abstract

Background: Early detection and treatment decreases HIV transmission rates and leads to risk reduction in those who are diagnosed. HIV-infected Guatemalans typically present with late-stage disease. Objective: We employed qualitative methods to explore barriers to HIV testing in Guatemala. Methods: In depth, qualitative interviews were conducted in an HIV testing and treatment facility in Guatemala City. These were analyzed using the methods of Grounded Theory. Results: Four major barriers impeded HIV testing in our subjects: psychological factors, stigma/discrimination, gender roles/machismo, and systemic barriers to care. Many of our patients’ fears were grounded in a reality of discrimination, while the systemic problems of the healthcare system reflected misunderstandings and fears on the part of healthcare workers. Discussion: Our findings are consonant with the international literature. Our narrative suggested potential interventions; presenting HIV testing as a way to “save one’s life” instead of an “automatic death sentence” might foster HIV testing and earlier diagnosis

Published
2017

7. HPTN 062: A Pilot Randomized Controlled Trial Exploring the Effect of a Motivational-Interviewing Intervention on Sexual Behavior among Individuals with Acute HIV Infection in Lilongwe, Malawi.

Author

Audrey Pettifor, Amy Corneli, Gift Kamanga, Kevin McKenna, Nora E Rosenberg, Xuesong Yu, San-San Ou, Cecilia Massa, Patricia Wiyo, Diana Lynn, Jenae Tharaldson, Carol Golin, Irving Hoffman, and HPTN 062 Study Protocol Team

Subjects
Medicine, Science
Abstract

OBJECTIVE:We pilot tested a Motivational Interviewing (MI) -based counseling intervention for individuals with Acute HIV Infection (AHI) to reduce risky sexual behavior in Lilongwe, Malawi. METHODS:Twenty-eight individuals diagnosed with AHI were randomized to receive either brief education alone, or the brief education plus the MI-based intervention, called Uphungu Wanga. Participants in Uphungu Wanga received four sessions delivered on the day of diagnosis, three days later and at weeks 1 and 2 with a booster session at week 8; participants were followed for 24 weeks from diagnosis. An interviewer administered quantitative questionnaire was conducted at baseline and at weeks 2, 4, 8, 12, 16, 20 and 24. Semi-structured qualitative interviews (SSI) were conducted at weeks 2, 8, 12, and 24. RESULTS:The majority of participants in both arms reported rapid and sustained behavior change following diagnosis with AHI. Very few participants reported having sex without a condom after diagnosis. Participants reported a trend towards fewer sex partners and abstaining from sex during study follow-up. Participants in the MI-based arm provided concrete examples of risk reduction strategies in the SSIs while those in the brief education arm primarily described reducing risk behavior, suggesting that the MI-based group may have acquired more risk reduction skills. CONCLUSIONS:Individuals in both study arms reduced risky sexual behaviors after diagnosis with AHI. We found few major differences between study arms during the 6-month follow up period in self-reported sexual behaviors therefore a MI-based intervention may not be needed to trigger behavior change following AHI. However, comparing the MI-based intervention to repeated brief education sessions made it difficult to assess the potential benefit of an MI-based intervention in a setting where standard counseling often consists of one post-test session. Nevertheless, provision of counseling immediately following diagnosis with HIV to support behavior change should remain a priority. TRIAL REGISTRATION:ClinicalTrials.gov NCT01197027.

Published
2015
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8. Risk Factors for Increased Stent-associated Symptoms Following Ureteroscopy for Urinary Stones: Results From STENTS

Author

Jonathan D. Harper, Alana C. Desai, Naim M. Maalouf, Hongqiu Yang, Jodi A. Antonelli, Gregory E. Tasian, H. Henry Lai, Peter P. Reese, Michele Curatolo, Ziya Kirkali, Hussein R. Al-Khalidi, Hunter Wessells, Charles D. Scales, Justin Ziemba, Emily Funsten, Adam Mussell, Rebecca McCune, Salima Shah, Arushi Jain, Antoine Selman-Fermin, Brett A. Johnson, Margaret S. Pearle, Linda A. Baker, Brooke Piskator, Joyce Obiaro, Cynthia Rangel, Martinez Hill, Todd Edwards, Mathew Sorensen, Robert Sweet, Tristan Baxter, Holly Covert, Elsa Ayala, Lisa Flint, Grace Cho, Grace Marshall, Kefu Du, Susan Mueller, Linda Black, Aleksandra Klim, Amy Corneli, Bryce Reeve, Kevin Weinfurt, Davy Andersen, Laura Johnson, Andrew Dodd, Omar Thompson, Carrie Dombeck, Kevin McKenna, Teri Swezey, and Christopher Mullins

Subjects
Urology
Published
2023
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11. Initial Content Validation and Roadmap for a New Patient-Reported Outcome Measure of Pain Intensity

Author

Dale J. Langford, Jennifer S. Gewandter, Dagmar Amtmann, Bryce B. Reeve, Amy Corneli, Kevin McKenna, Teresa Swezey, Molly McFatrich, Mark P. Jensen, Dennis C. Turk, and Robert H. Dworkin

Subjects
Clinical Trials as Topic, Anesthesiology and Pain Medicine, Neurology, Humans, Reproducibility of Results, Patient Reported Outcome Measures, Neurology (clinical), Chronic Pain, Acute Pain, Pain Measurement
Abstract

Measures of pain intensity (eg, numeric rating scales [NRS]) are widely used in clinical research and practice. While these measures have evidence for validity and reliability, poor standardization of instructions, and response options limits precision of pain assessment, allows for inconsistency in interpretation, and presents a challenge for comparison and aggregation of study results. Despite these pitfalls, the 0 to 10 NRS remains the most commonly used primary outcome measure in clinical trials of pain treatments and is the core measure recommended by regulatory agencies. The purpose of this study was to describe the first phase in the development of a pain intensity measure that is easily interpretable, psychometrically sound, and that adheres to FDA qualification processes. The Analgesic, Anesthetic, and Addiction Clinical Trial, Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership conducted concept elicitation interviews (N = 44; 22 with acute pain; 22 with chronic pain) to understand the patient perspective on rating pain intensity and to identify actionable suggestions for improved clarity and meaningfulness of instructions, recall periods, and response options. This article summarizes interview findings, describes how patient input and FDA feedback informed preliminary candidate measures, and provides an overview of the FDA qualification process. PERSPECTIVE: Concept elicitation interviews informed the development of content-valid candidate measures of acute and chronic pain intensity for planned use in clinical trials of pain treatments, and comprise the initial stage in FDA clinical outcome assessment qualification. Measures will subsequently be evaluated through cognitive interviews and a series of psychometric studies.

Published
2022
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12. Patients’ Experiences with the Removal of a Ureteral Stent: Insights from In-Depth Interviews with Participants in the USDRN STENTS Qualitative Cohort Study

Author

Carrie Dombeck, Charles D. Scales, Kevin McKenna, Teresa Swezey, Jonathan D. Harper, Jodi A. Antonelli, Alana C. Desai, H. Henry Lai, Rebecca McCune, Michele Curatolo, Hussein R. Al-Khalidi, Naim M. Maalouf, Peter P. Reese, Hunter Wessells, Ziya Kirkali, and Amy Corneli

Subjects
Urology
Published
2023
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13. Up-dosing of secukinumab to 2-weekly results in superior efficacy in patients with severe psoriasis weighing 90 kg or more: a real-world prospective observational study

Author

Niamh McGuire, Shahd Elamin, Pamela Gough, Nicola Cooke, Conor McGrath, Kevin McKenna, and Donal O’Kane

Subjects
Dermatology
Abstract

This is the first real-world observational study demonstrating the superior efficacy of 2-weekly (Q2W) secukinumab dosing in patients with severe psoriasis greater than 90kg.

Published
2023
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15. Caregivers of Black and Latino/a/x Students and School Personnel Perspectives on School-Based SARS-CoV-2 Testing: Implications for Testing and Test-to-Stay Programs in K-12 Schools

Author

Amy, Corneli, Kevin, McKenna, Carrie, Dombeck, Nneka, Molokwu, Jamilah, Taylor, Lorraine, Vergara, Daniel K, Benjamin, and Kanecia O, Zimmerman

Abstract

"Test-to-stay" (TTS) is an effective approach for keeping students in school post-exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To prepare for school-based SARS-CoV-2 testing, we implemented formative research to gather perspectives on school-based testing among school personnel, as well as caregivers of Black and Latino/a/x students given systemic racism, existing school inequalities, and the disproportionate effect of COVID-19 on Black and Latino/a/x populations.We conducted in-depth interviews with caregivers of K-12 grade Black and Latino/a/x students and focus group discussions with K-12 school personnel. We described the forthcoming school-based SARS-CoV-2 testing program and explored potential benefits and concerns, including concerns about testing-related stigma and discrimination, particularly toward Black and Latino/a/x students, and implementation recommendations.Perceived testing benefits included school community reassurance and preventing school outbreaks. Concerns included potential student anxiety, classroom disruption, inaccurate results, and limited information for caregivers. Some participants mentioned that testing-related stigma and discrimination could happen based on the testing selection process or results but not due to race or ethnicity. Participants provided numerous testing recommendations, including suggestions to prevent negative outcomes.Participants believed that stigma and discrimination from SARS-CoV-2 testing is possible, although differential treatment based on race or ethnicity was not anticipated. Participants' narratives provide support for school-based testing and the testing component of TTS.

Published
2022

16. Inclusion of Caregivers in Veterans’ Care: A Critical Literature Review

Author

Nina R. Sperber, Nathan A. Boucher, Kimberly Peacock, Kevin McKenna, Courtney Harold Van Houtven, Roxana E. Delgado, Megan Shepherd-Banigan, and Megan Van Noord

Subjects
Constant comparison, Communication, 030503 health policy & services, Health Policy, media_common.quotation_subject, 03 medical and health sciences, 0302 clinical medicine, Caregivers, Extant taxon, Nursing, Content analysis, Conceptual model, Humans, In patient, Quality (business), 030212 general & internal medicine, 0305 other medical science, Psychology, Inclusion (education), Veterans, media_common, Health care quality
Abstract

More direct inclusion of informal caregivers (i.e., family, friends) in patients’ care will make care more patient- and family-centered and has the potential to improve overall quality of care for patients. We need to understand what potentially comprises “inclusive care” so that we can define what “inclusive care” is and develop targets for care quality metrics. We conducted a critical literature review to identify key components of “caregiver inclusion.” Focusing on extant literature from 2005 to 2017, 35 papers met inclusion criteria. Directed content analysis with constant comparison was used to identify major themes related to a concept of “inclusive care.” Our analysis indicates that “inclusive care” entails five components: clear definition of caregiver role, system level policies for inclusion, explicit involvement of caregiver, provider assessment of caregiver capability, and mutuality in caregiver–provider communication. We discuss the evidence behind these five components using the Donabedian health care quality conceptual model.

Published
2020
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17. Research Use of Electronic Health Records: Patients’ Views on Alternative Approaches to Permission

Author

Kevin McKenna, Kathleen M. Brelsford, Ross D. Graham, Laura M. Beskow, Catherine M. Hammack-Aviran, and Zachary M. Lampron

Subjects
Adult, Male, Health (social science), Adolescent, Internet privacy, Permission, Trust, 0603 philosophy, ethics and religion, Article, Ethics, Research, law.invention, Young Adult, 03 medical and health sciences, Mississippi, law, Surveys and Questionnaires, Health care, North Carolina, Electronic Health Records, Humans, Confidentiality, Qualitative Research, Aged, Aged, 80 and over, Appalachian Region, 0303 health sciences, Research ethics, Informed Consent, business.industry, Data Collection, Health Policy, 030305 genetics & heredity, Usability, 06 humanities and the arts, Awareness, Middle Aged, Philosophy, Attitude, Privacy, Research Design, Public trust, CLARITY, Female, 060301 applied ethics, business, Psychology, Qualitative research
Abstract

Background: The increased use of electronic health records (EHRs) has resulted in new opportunities for research, but also raises concerns regarding privacy, confidentiality, and patient awareness. Because public trust is essential to the success of the research enterprise, patient perspectives are essential to the development and implementation of ethical approaches to the research use of EHRs. Yet, little is known about patients' views and expectations regarding various approaches to seeking permission for research use of their EHR data. Methods: We conducted semi-structured interviews with 120 patients in four counties in diverse regions of the southeastern United States: Appalachia, the Mississippi Delta, and the Piedmont area of North Carolina. We asked participants to consider, from multiple stakeholder perspectives, the advantages and disadvantages of three approaches to notifying patients of, or obtaining permission for, research use of their EHR data; whether they believed it would be acceptable if their healthcare organization used each approach; and which approach would be most appropriate. Results: Nearly all participants said General Notification, Broad Permission, and Categorical Permission would each be acceptable approaches to notification of, or permission for, EHR research. Over half identified Broad Permission as the most appropriate approach. Across all of these discussions, major themes included the importance of clarity, simplicity, and usability of patient-facing materials, as well as the level of transparency, trustworthiness, and respect for patients the approach conveys. Conclusions: Our findings help to inform the development and implementation of ethical approaches to the research use of EHRs by identifying key patient considerations regarding various approaches to permission and suggesting potential actions for healthcare organizations and researchers.

Published
2020
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18. Location of Power within Psychiatry: A Fifty-Year Journey as Represented in Film

Author

Kevin McKenna, Ian Needham, Jeanne E Kimpel, and Lois Biggin Moylan

Subjects
Psychiatry, medicine.medical_specialty, Hollywood, History, 030504 nursing, Mental Disorders, Motion Pictures, Social change, Patient rights, History, 20th Century, Mental health, United States, 030227 psychiatry, Power (social and political), 03 medical and health sciences, 0302 clinical medicine, Western europe, medicine, Humans, Pshychiatric Mental Health, 0305 other medical science, Period (music)
Abstract

Over the last half of the twentieth century, many advances in the field of psychiatry and mental health have occurred and continue today. Among these developments are the increasing recognition of patient rights and the expanding role of psychiatric nurses. This paper presents a view of how these changes have been reflected in film over a period of fifty years in both documentary and Hollywood movies. Discussion of advances in psychiatry, as identified in the selected films, is presented against the background of social change that was occurring in the United States and Western Europe during this period.

Published
2020
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19. Leveraging institutional support for family caregivers to meet the health and vocational needs of persons with disabilities

Author

Nina R. Sperber, Kevin McKenna, Megan Shepherd-Banigan, Terri K. Pogoda, and Courtney Harold Van Houtven

Subjects
Adult, Male, Staffing, Institutional support, Article, 03 medical and health sciences, Social support, 0302 clinical medicine, Nursing, Humans, Disabled Persons, Family, 030212 general & internal medicine, Veterans Affairs, health care economics and organizations, General Nursing, Aged, Veterans, Aged, 80 and over, 030504 nursing, Family caregivers, Qualitative interviews, Social Support, Middle Aged, United States, humanities, United States Department of Veterans Affairs, Caregivers, Vocational education, Female, 0305 other medical science, Psychology, Needs Assessment, Qualitative research
Abstract

Background Family caregivers might enhance veteran engagement in health and nonhealth services (i.e., vocational/educational assistance). Purpose To describe how veterans with disabilities perceive their recovery needs, identify types of social support from caregivers that help veterans engage in Veterans Affairs (VA) health and nonhealth services, and explore participant views of VA institutional support for caregivers to help veterans engage in these services. Methods Joint in-depth qualitative interviews with U.S. veterans and family caregivers (n = 26). Findings Caregivers performed social support functions that helped veterans engage in health and vocational/educational services and institutional support from VA enhanced caregivers’ capacity. Discussion Caregivers are well positioned to align health and nonhealth services with patient needs to enhance recovery. Staffing a point person for caregivers within the health system is key to help families develop a coordinated plan of treatment and services to improve patient success across health and nonhealth domains. Nurses are well suited to perform this role.

Published
2020
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22. 1113 Patient and Physician Perspectives of Lupus Flare

Author

Jennifer L. Rogers, Nneka Molokwu, Amy Corneli, Lisa G. Criscione-Schreiber, Mithunan Maheswaranthan, Kevin McKenna, Megan E.B. Clowse, Kai Sun, Teresa Swezey, David S. Pisetsky, Summer Starling, Rebecca E Sadun, Amanda M Eudy, and Jayanth Doss

Subjects
medicine.medical_specialty, Lupus Flare, business.industry, Medicine, business, Dermatology
Published
2021
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23. Quantitative analysis of phenotypic elements augments traditional electroclinical classification of common familial epilepsies

Author

Orrin Devinsky, Samuel F. Berkovic, Catharine Freyer, Annapurna Poduri, Eric B. Geller, Amos D. Korczyn, Heidi E. Kirsch, Nathan B. Fountain, Rosemary Burgess, Jack M. Parent, Jocelyn F. Bautista, Susannah T. Bellows, Robert C. Knowlton, David Goldstein, Dennis J. Dlugos, Heather C Mefford, Anthony G Marson, Mike Smith, Sabrina Cristofaro, Erin L. Heinzen, Bassel Abou-Khalil, Michael P. Epstein, Douglas E. Crompton, Eileen P.G. Vining, Kevin McKenna, Steven Petrou, Anu Venkat, Eric H. Kossoff, Gretchen Von Allmen, Sheryl R. Haut, Ruben Kuzniecky, Juliann M. Paolicchi, Colin A Ellis, Rani K. Singh, Simon Glynn, Daniel H. Lowenstein, Liu Lin Thio, Lynette G. Sadleir, Rebecca Loeb, Norman Delanty, Terence J. O'Brien, Paul V. Motika, Peter Widdess-Walsh, Sara Kivity, Gregory D. Cascino, Slavé Petrovski, Ruth Ottman, Micheline Gravel, Andrew S. Allen, Jerry J. Shih, Ingrid E. Scheffer, Joseph I Sirven, William O. Pickrell, Tracy A. Glauser, Judith L.Z. Weisenberg, Judith Bluvstein, Zaid Afawi, Phil Smith, Kevin F. Haas, Mark McCormack, Hadassa Goldberg-Stern, Sarah Paterson, Melodie R. Winawer, Mark I. Rees, Saul A. Mullen, Patrick Cossette, and Rhys H. Thomas

Subjects
Male, 0301 basic medicine, Concordance, Electroencephalography, Article, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, medicine, Humans, Medical history, Generalized epilepsy, medicine.diagnostic_test, Seizure types, business.industry, Family aggregation, medicine.disease, Latent class model, Pedigree, Phenotype, 030104 developmental biology, Neurology, Latent Class Analysis, Female, Neurology (clinical), business, Epileptic Syndromes, 030217 neurology & neurosurgery, Clinical psychology
Abstract

OBJECTIVE: Classification of epilepsy into types and subtypes is important for both clinical care and research into underlying disease mechanisms. A quantitative, data-driven approach may augment traditional electroclinical classification and shed new light on existing classification frameworks. METHODS: We used latent class analysis, a statistical method that assigns subjects into groups called latent classes based on phenotypic elements, to classify individuals with common familial epilepsies from the Epi4K Multiplex Families study. Phenotypic elements included seizure types, seizure symptoms, and other elements of the medical history. We compared class assignments to traditional electroclinical classifications and assessed familial aggregation of latent classes. RESULTS: A total of 1120 subjects with epilepsy were assigned to five latent classes. Classes 1 and 2 contained subjects with generalized epilepsy, largely reflecting the distinction between absence epilepsies and younger onset (class 1) versus myoclonic epilepsies and older onset (class 2). Classes 3 and 4 contained subjects with focal epilepsies, and in contrast to classes 1 and 2, these did not adhere as closely to clinically defined focal epilepsy subtypes. Class 5 contained nearly all subjects with febrile seizures plus or unknown epilepsy type, as well as a few subjects with generalized epilepsy and a few with focal epilepsy. Family concordance of latent classes was similar to or greater than concordance of clinically defined epilepsy types. SIGNIFICANCE: Quantitative classification of epilepsy has the potential to augment traditional electroclinical classification by (1) combining some syndromes into a single class, (2) splitting some syndromes into different classes, (3) helping to classify subjects who could not be classified clinically, and (4) defining the boundaries of clinically defined classifications. This approach can guide future research, including molecular genetic studies, by identifying homogeneous sets of individuals that may share underlying disease mechanisms.

Published
2019
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24. Including Family Caregivers In Seriously Ill Veterans’ Care: A Mixed-Methods Study

Author

Roxana E. Delgado, Kevin McKenna, Courtney Harold Van Houtven, Nathan A. Boucher, Margaret Kabat, Madison Moore, Nina R. Sperber, Rachael Barrett, and Megan Shepherd-Banigan

Subjects
Male, 03 medical and health sciences, 0302 clinical medicine, Nursing, Surveys and Questionnaires, Health care, Humans, 030212 general & internal medicine, Veterans Affairs, Human services, Veterans, Patient Care Team, business.industry, Family caregivers, Communication, 030503 health policy & services, Health Policy, Social Support, Quality Improvement, United States, United States Department of Veterans Affairs, Long-term care, Caregivers, Chronic Disease, Workforce, Female, 0305 other medical science, Psychology, business, Inclusion (education)
Abstract

Family caregivers often serve as unpaid members of the home and community-based care workforce for people with serious illness; as key partners in the home-clinic continuum, they should be included in health care teams. The Campaign for Inclusive Care is an initiative within the Veterans Affairs health care system to improve provider practices for including caregivers of military members in treatment planning and decisions. We defined inclusive care using a literature review, provider interviews, and a caregiver survey. We found that inclusive care involves clear definition of the caregiver role, system policies for inclusion, assessment of caregivers' capacity, explicit involvement of caregivers, and mutuality in caregiver-provider communication. We recommend solutions based on this definition that can inform development of a national caregiver strategy, required of the Department of Health and Human Services by the Recognize, Assist, Include, Support, and Engage Family Caregivers Act of 2018.

Published
2019
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25. Family Caregiver and Provider Perspectives on Inclusive Care: Aligning Needs and Expectations

Author

Leah Christensen, Nina R. Sperber, Coleton Whitaker, Kevin McKenna, Roxana E. Delgado, Megan Shepherd-Banigan, and Nathan A. Boucher

Subjects
Health Knowledge, Attitudes, Practice, Health Services Needs and Demand, Vulnerable adult, business.industry, Family caregivers, media_common.quotation_subject, Health Personnel, Public Health, Environmental and Occupational Health, Communications management, Interview data, Interviews as Topic, Nursing, Caregivers, Patient-Centered Care, Health care, Humans, Quality (business), business, Psychology, Inclusion (education), Veterans Affairs, Qualitative Research, media_common
Abstract

BACKGROUND Home-based and community-based health care for individuals with complex medical conditions is often provided by family caregivers. Yet caregivers often are not meaningfully included in interactions with clinical health care teams. Inclusive care means inviting the caregiver to participate in shared decision-making and treatment planning. For aging or medically vulnerable adults, caregiver inclusion is an important facet of patient-centered care. METHODS We apply a mixed-methods approach using a survey (n=50) and semistructured interview data (n=13) from a national sample of caregivers of veterans and semistructured interview data from (n=24) providers from 3 Veterans Affairs regional networks. We elicited data from caregivers about their experiences with inclusive care and how providers communicate with them and assess their capacity. We juxtaposed these data with provider perspectives to see where there was alignment. FINDINGS We determined that caregivers play important roles in trust-building, communications management, implementation of care plans at home or in the community, and improving the care of care recipients-while maintaining a balance between competing tensions. CONCLUSIONS Our findings suggest that expanding inclusive care could improve care quality and health outcomes of individuals with complex health care needs. Further, our findings bolster recent policy efforts at the federal and state levels to increase recognition of caregivers as key members of the health care team.

Published
2021

26. Stakeholder Experiences with the Single IRB Review Process and Recommendations for Food and Drug Administration Guidance

Author

Carrie B. Dombeck, Amy Corneli, Kevin McKenna, and Sara B. Calvert

Subjects
Health (social science), Standardization, Context (language use), Article, Consistency (negotiation), Common Rule, institutional review boards (IRBs), Humans, human research ethics, Human services, business.industry, United States Food and Drug Administration, Communication, Stakeholder, Uncertainty, Articles, Public relations, Reference Standards, Institutional review board, United States, Clinical research, Food and Drug Administration (FDA), human subjects research, single institutional review boards (sIRBs), business, Ethics Committees, Research, revised Common Rule
Abstract

The revised Common Rule requires using a single institutional review board (sIRB) for U.S.‐based, multisite, nonexempt, federally conducted or supported research with human participants. The 21st Century Cures Act directs the Department of Health and Human Services (HHS) to harmonize differences between HHS and the U.S. Food and Drug Administration (FDA) regulations governing research with humans. Anticipating that the FDA may update its 2006 centralized IRB guidance, we conducted interviews with 34 stakeholders engaged in FDA‐regulated clinical research to identify benefits and challenges of using sIRBs and to gather recommendations for revising the FDA's guidance. The main benefits were consistency and standardization, speed and efficiency, and streamlining and simplification. The main challenges were uncertainty at local institutions, including addressing local context; decreased timeliness of the research review process; variable processes; and insufficient communication. Several recommendations for FDA guidance focused on the local context and communication plans. Findings suggest that the sIRB review process may be gaining efficiency although challenges remain.

Published
2021

27. Distinct gene-set burden patterns underlie common generalized and focal epilepsies

Author

Mahmoud Koko, Roland Krause, Thomas Sander, Dheeraj Reddy Bobbili, Michael Nothnagel, Patrick May, Holger Lerche, Yen-Chen Anne Feng, Daniel P Howrigan, Liam E Abbott, Katherine Tashman, Felecia Cerrato, Tarjinder Singh, Henrike Heyne, Andrea Byrnes, Claire Churchhouse, Nick Watts, Matthew Solomonson, Dennis Lal, Erin L Heinzen, Ryan S Dhindsa, Kate E Stanley, Gianpiero L Cavalleri, Hakon Hakonarson, Ingo Helbig, Sarah Weckhuysen, Slavé Petrovski, Sitharthan Kamalakaran, Sanjay M Sisodiya, Patrick Cossette, Chris Cotsapas, Peter DeJonghe, Tracy Dixon-Salazar, Renzo Guerrini, Patrick Kwan, Anthony G Marson, Randy Stewart, Chantal Depondt, Dennis J Dlugos, Ingrid E Scheffer, Pasquale Striano, Catharine Freyer, Kevin McKenna, Brigid M Regan, Susannah T Bellows, Costin Leu, Caitlin A Bennett, Esther M C Johns, Alexandra Macdonald, Hannah Shilling, Rosemary Burgess, Dorien Weckhuysen, Melanie Bahlo, Terence J O'Brien, Marian Todaro, Hannah Stamberger, Danielle M Andrade, Tara R Sadoway, Kelly Mo, Heinz Krestel, Sabina Gallati, Savvas S Papacostas, Ioanna Kousiappa, George A Tanteles, Katalin Štěrbová, Markéta Vlčková, Lucie Sedláčková, Petra Laššuthová, Karl Martin Klein, Felix Rosenow, Philipp S Reif, Susanne Knake, Wolfram S Kunz, Gábor Zsurka, Christian E Elger, Jürgen Bauer, Michael Rademacher, Manuela Pendziwiat, Hiltrud Muhle, Annika Rademacher, Andreas vanBaalen, Sarah vonSpiczak, Ulrich Stephani, Zaid Afawi, Amos D Korczyn, Moien Kanaan, Christina Canavati, Gerhard Kurlemann, Karen Müller-Schlüter, Gerhard Kluger, Martin Häusler, Ilan Blatt, Johannes R Lemke, Ilona Krey, Yvonne G Weber, Stefan Wolking, Felicitas Becker, Christian Hengsbach, Sarah Rau, Ana F Maisch, Bernhard J Steinhoff, Andreas Schulze-Bonhage, Susanne Schubert-Bast, Herbert Schreiber, Ingo Borggräfe, Christoph J Schankin, Thomas Mayer, Rudolf Korinthenberg, Knut Brockmann, Dieter Dennig, Rene Madeleyn, Reetta Kälviäinen, Pia Auvinen, Anni Saarela, Tarja Linnankivi, Anna-Elina Lehesjoki, Mark I Rees, Seo-Kyung Chung, William O Pickrell, Robert Powell, Natascha Schneider, Simona Balestrini, Sara Zagaglia, Vera Braatz, Michael R Johnson, Pauls Auce, Graeme J Sills, Larry W Baum, Pak C Sham, Stacey S Cherny, Colin H T Lui, Nina Barišić, Norman Delanty, Colin P Doherty, Arif Shukralla, Mark McCormack, Hany El-Naggar, Laura Canafoglia, Silvana Franceschetti, Barbara Castellotti, Tiziana Granata, Federico Zara, Michele Iacomino, Francesca Madia, Maria Stella Vari, Maria Margherita Mancardi, Vincenzo Salpietro, Francesca Bisulli, Paolo Tinuper, Laura Licchetta, Tommaso Pippucci, Carlotta Stipa, Raffaella Minardi, Antonio Gambardella, Angelo Labate, Grazia Annesi, Lorella Manna, Monica Gagliardi, Elena Parrini, Davide Mei, Annalisa Vetro, Claudia Bianchini, Martino Montomoli, Viola Doccini, Carla Marini, Toshimitsu Suzuki, Yushi Inoue, Kazuhiro Yamakawa, Birute Tumiene, Lynette G Sadleir, Chontelle King, Emily Mountier, Hande S Caglayan, Mutluay Arslan, Zuhal Yapıcı, Uluc Yis, Pınar Topaloglu, Bulent Kara, Dilsad Turkdogan, Aslı Gundogdu-Eken, Nerses Bebek, Sibel Uğur-İşeri, Betül Baykan, Barış Salman, Garen Haryanyan, Emrah Yücesan, Yeşim Kesim, Çiğdem Özkara, Annapurna Poduri, Beth R Shiedley, Catherine Shain, Russell J Buono, Thomas N Ferraro, Michael R Sperling, Warren Lo, Michael Privitera, Jacqueline A French, Steven Schachter, Ruben I Kuzniecky, Orrin Devinsky, Manu Hegde, Pouya Khankhanian, Katherine L Helbig, Colin A Ellis, Gianfranco Spalletta, Fabrizio Piras, Federica Piras, Tommaso Gili, Valentina Ciullo, Andreas Reif, Andrew McQuillin, Nick Bass, Andrew McIntosh, Douglas Blackwood, Mandy Johnstone, Aarno Palotie, Michele T Pato, Carlos N Pato, Evelyn J Bromet, Celia Barreto Carvalho, Eric D Achtyes, Maria Helena Azevedo, Roman Kotov, Douglas S Lehrer, Dolores Malaspina, Stephen R Marder, Helena Medeiros, Christopher P Morley, Diana O Perkins, Janet L Sobell, Peter F Buckley, Fabio Macciardi, Mark H Rapaport, James A Knowles, Genomic Psychiatry Cohort, Ayman H Fanous, Steven A McCarroll, Namrata Gupta, Stacey B Gabriel, Mark J Daly, Eric S Lander, Daniel H Lowenstein, David B Goldstein, Samuel F Berkovic, Benjamin M Neale, Epi25 Collaborative, Koko M., Krause R., Sander T., Bobbili D.R., Nothnagel M., May P., Lerche H., Bisulli F., Tinuper P., Pippucci T., Abbott, Liam E., Hengsbach, Christian, Rau, Sarah, Maisch, Ana F., Steinhoff, Bernhard J., Schulze-Bonhage, Andreas, Schubert-Bast, Susanne, Schreiber, Herbert, Borggräfe, Ingo, Schankin, Christoph J., Mayer, Thomas, Tashman, Katherine, Korinthenberg, Rudolf, Brockmann, Knut, Kurlemann, Gerhard, Dennig, Dieter, Madeleyn, Rene, Kälviäinen, Reetta, Auvinen, Pia, Saarela, Anni, Linnankivi, Tarja, Lehesjoki, Anna-Elina, Cerrato, Felecia, Rees, Mark I., Chung, Seo-Kyung, Pickrell, William O., Powell, Robert, Schneider, Natascha, Balestrini, Simona, Zagaglia, Sara, Braatz, Vera, Johnson, Michael R., Auce, Pauls, Singh, Tarjinder, Sills, Graeme J., Baum, Larry W., Sham, Pak C., Cherny, Stacey S., Lui, Colin H. T., Barišic, Nina, Delanty, Norman, Doherty, Colin P., Shukralla, Arif, McCormack, Mark, Heyne, Henrike, El-Naggar, Hany, Canafoglia, Laura, Franceschetti, Silvana, Castellotti, Barbara, Granata, Tiziana, Zara, Federico, Iacomino, Michele, Madia, Francesca, Vari, Maria Stella, Mancardi, Maria Margherita, Byrnes, Andrea, Salpietro, Vincenzo, Bisulli, Francesca, Tinuper, Paolo, Licchetta, Laura, Pippucci, Tommaso, Stipa, Carlotta, Minardi, Raffaella, Gambardella, Antonio, Labate, Angelo, Annesi, Grazia, Churchhouse, Claire, Manna, Lorella, Gagliardi, Monica, Parrini, Elena, Mei, Davide, Vetro, Annalisa, Bianchini, Claudia, Montomoli, Martino, Doccini, Viola, Marini, Carla, Suzuki, Toshimitsu, Watts, Nick, Inoue, Yushi, Yamakawa, Kazuhiro, Tumiene, Birute, Sadleir, Lynette G., King, Chontelle, Mountier, Emily, Caglayan, Hande S., Arslan, Mutluay, Yapici, Zuhal, Yis, Uluc, Solomonson, Matthew, Topaloglu, Pinar, Kara, Bulent, Turkdogan, Dilsad, Gundogdu-Eken, Asli, Bebek, Nerses, Ugur-Iseri, Sibel, Baykan, Betül, Salman, Baris, Haryanyan, Garen, Yücesan, Emrah, Lal, Dennis, Kesim, Yesim, Özkara, Çigdem, Poduri, Annapurna, Shiedley, Beth R., Shain, Catherine, Buono, Russell J., Ferraro, Thomas N., Sperling, Michael R., Lo, Warren, Privitera, Michael, Heinzen, Erin L., French, Jacqueline A., Schachter, Steven, Kuzniecky, Ruben I., Devinsky, Orrin, Hegde, Manu, Khankhanian, Pouya, Helbig, Katherine L., Ellis, Colin A., Spalletta, Gianfranco, Piras, Fabrizio, Dhindsa, Ryan S., Piras, Federica, Gili, Tommaso, Ciullo, Valentina, Reif, Andreas, McQuillin, Andrew, Bass, Nick, McIntosh, Andrew, Blackwood, Douglas, Johnstone, Mandy, Palotie, Aarno, Stanley, Kate E., Pato, Michele T., Pato, Carlos N., Bromet, Evelyn J., Carvalho, Celia Barreto, Achtyes, Eric D., Azevedo, Maria Helena, Kotov, Roman, Lehrer, Douglas S., Malaspina, Dolores, Marder, Stephen R., Cavalleri, Gianpiero L., Medeiros, Helena, Morley, Christopher P., Perkins, Diana O., Sobell, Janet L., Buckley, Peter F., Macciardi, Fabio, Rapaport, Mark H., Knowles, James A., Cohort, Genomic Psychiatry, Fanous, Ayman H., Hakonarson, Hakon, McCarroll, Steven A., Gupta, Namrata, Gabriel, Stacey B., Daly, Mark J., Lander, Eric S., Lowenstein, Daniel H., Goldstein, David B., Lerche, Holger, Berkovic, Samuel F., Neale, Benjamin M., Helbig, Ingo, Krause, Roland, May, Patrick, Weckhuysen, Sarah, Petrovski, Slavé, Kamalakaran, Sitharthan, Sisodiya, Sanjay M., Cossette, Patrick, Cotsapas, Chris, DeJonghe, Peter, Dixon-Salazar, Tracy, Guerrini, Renzo, Kwan, Patrick, Marson, Anthony G., Stewart, Randy, Depondt, Chantal, Dlugos, Dennis J., Scheffer, Ingrid E., Striano, Pasquale, Freyer, Catharine, McKenna, Kevin, Regan, Brigid M., Bellows, Susannah T., Leu, Costin, Bennett, Caitlin A., Johns, Esther M. C., Macdonald, Alexandra, Shilling, Hannah, Burgess, Rosemary, Weckhuysen, Dorien, Bahlo, Melanie, O'Brien, Terence J., Todaro, Marian, Stamberger, Hannah, Andrade, Danielle M., Sadoway, Tara R., Mo, Kelly, Krestel, Heinz, Gallati, Sabina, Papacostas, Savvas S., Kousiappa, Ioanna, Tanteles, George A., Šterbová, Katalin, Vlcková, Markéta, Sedlácková, Lucie, Laššuthová, Petra, Klein, Karl Martin, Rosenow, Felix, Reif, Philipp S., Knake, Susanne, Kunz, Wolfram S., Zsurka, Gábor, Elger, Christian E., Bauer, Jürgen, Rademacher, Michael, Feng, Yen-Chen Anne, Pendziwiat, Manuela, Muhle, Hiltrud, Rademacher, Annika, van Baalen, Andreas, von Spiczak, Sarah, Stephani, Ulrich, Afawi, Zaid, Korczyn, Amos D., Kanaan, Moien, Canavati, Christina, Howrigan, Daniel P., Müller-Schlüter, Karen, Kluger, Gerhard, Häusler, Martin, Blatt, Ilan, Lemke, Johannes R., Krey, Ilona, Weber, Yvonne G., Wolking, Stefan, Becker, Felicitas, DFG Research Unit FOR-2715 (Germany), FNR (Luxembourg), NHGRI (US), NHLBI (US), DAAD (Germany). [sponsor], and Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) [research center]

Subjects
Exome sequencing, Male, Medicine (General), Neurology [D14] [Human health sciences], Gene-set, Genome-wide association study, Disease, Biology, Epileptogenesis, General Biochemistry, Genetics and Molecular Biology, Whole Exome Sequencing, Epilepsy, R5-920, medicine, Missense mutation, Humans, Exome, Genetic Predisposition to Disease, Gene, Genetic association, Ultra-rare variant, Genetics, Neurologie [D14] [Sciences de la santé humaine], Burden analysis, Genetic Variation, General Medicine, medicine.disease, Ultra-rare variants, Gene-sets, Case-Control Studies, Medicine, epilepsy, Epilepsy, Generalized, Female, Genetics & genetic processes [F10] [Life sciences], Epilepsies, Partial, Human medicine, Burden analysi, Génétique & processus génétiques [F10] [Sciences du vivant], Case-Control Studie, Research Paper, Genome-Wide Association Study, Human
Abstract

EBioMedicine 72, 103588 (2021). doi:10.1016/j.ebiom.2021.103588, Published by Elsevier, Amsterdam [u.a.]

Published
2021
Full Text
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28. Sub-genic intolerance, ClinVar, and the epilepsies: A whole-exome sequencing study of 29,165 individuals

Author

Joshua E. Motelow, Gundula Povysil, Ryan S. Dhindsa, Kate E. Stanley, Andrew S. Al- len, Yen-Chen Anne Feng, Daniel P. Howrigan, Liam E. Abbott, Ka- therine Tashman, Felecia Cerrato, Caroline Cusick, Tarjinder Singh, Henrike Heyne, Andrea E. Byrnes, Claire Churchhouse, Nick Watts, Matthew Solomonson, Dennis Lal, Namrata Gupta, Benjamin M. Neale, Gianpiero L. Cavalleri, Patrick Cossette, Chris Cotsapas, Peter De Jonghe, Tracy Dixon-Salazar, Renzo Guerrini, Hakon Hakonarson, Erin L. Heinzen, Ingo Helbig, Patrick Kwan, Anthony G. Marson, Slave ? Petrovski, Sitharthan Kamalakaran, Sanjay M. Sisodiya, Randy Stewart, Sarah Weckhuysen, Chantal Depondt, Dennis J. Dlugos, Ingrid E. Scheffer, Pasquale Striano, Catharine Freyer, Roland Krause, Patrick May, Kevin McKenna, Brigid M. Regan, Caitlin A. Bennett, Costin Leu, Stephanie L. Leech, Terence J. O'Brien, Marian Todaro, Hannah Stamberger, Danielle M. Andrade, Quratulain Zulfiqar Ali, Tara R. Sadoway, Heinz Krestel, Andre ? Schaller, Savvas S. Papacostas, Ioanna Kou- siappa, George A. Tanteles, Yiolanda Christou, Katalin Sterbova ?, Marke ? ta Vlckova ?, Lucie Sedlackova, Petra Lassuthova ?, Karl Martin Klein, Felix Rosenow, Philipp S. Reif, Susanne Knake, Bernd A. Neubauer, Friedrich Zimprich, Martha Feucht, Eva M. Reinthaler, Wolfram S. Kunz, Ga ?bor Zsurka, Rainer Surges, Tobias Baumgart- ner, Randi von Wrede, Manuela Pendziwiat, Hiltrud Muhle, An- nika Rademacher, Andreas van Baalen, Sarah von Spiczak, Ulrich Stephani, Zaid Afawi, Amos D. Korczyn, Moien Kanaan, Christina Canavati, Gerhard Kurlemann, Karen Mu ?ller-Schlu ?ter, Gerhard Kluger, Martin Ha ?usler, Ilan Blatt, Johannes R. Lemke, Ilona Krey, Yvonne G. Weber, Stefan Wolking, Felicitas Becker, Stephan Lauxmann, Christian Boßelmann, Josua Kegele, Christian Hengs- bach, Sarah Rau, Bernhard J. Steinhoff, Andreas Schulze-Bonhage, IngoBorggra ?fe, ChristophJ.Schankin, SusanneSchubert-Bast, Herbert Schreiber, Thomas Mayer, Rudolf Korinthenberg, Knut Brockmann, Markus Wolff, Dieter Dennig, Rene Madeleyn, Reetta Ka ?lvia ?inen, Anni Saarela, Oskari Timonen, Tarja Linnankivi, Anna-Elina Lehesjoki, Sylvain Rheims, Gaetan Lesca, Philippe Ryvlin, Louis Maillard, Luc Valton, Philippe Derambure, Fabrice Bartolomei, Edouard Hirsch, Ve ?ronique Michel, Francine Chas- soux, Mark I. Rees, Seo-Kyung Chung, William O. Pickrell, Robert Powell, Mark D. Baker, Beata Fonferko-Shadrach, Charlotte Law- thom, Joseph Anderson, Natascha Schneider, Simona Balestrini, Sara Zagaglia, Vera Braatz, Michael R. Johnson, Pauls Auce, Graeme J. Sills, Larry W. Baum, Pak C. Sham, Stacey S. Cherny, Colin H.T. Lui, Norman Delanty, Colin P. Doherty, Arif Shukralla, Hany El-Naggar, Peter Widdess-Walsh, Nina Barisic, Laura 12 The American Journal of Human Genetics 108, 1-18, June 3, 2021 Please cite this article in press as: Epi25 Collaborative, Sub-genic intolerance, ClinVar, the epilepsies: A whole-exome sequencing study of 29, 165 individuals, The American Journal of Human Genetics (2021), https://doi.org/10.1016/j.ajhg.2021.04.009 Canafoglia, Silvana Franceschetti, Barbara Castellotti, Tiziana Granata, Francesca Ragona, Federico Zara, Michele Iacomino, An- tonella Riva, Francesca Madia, Maria Stella Vari, Vincenzo Salpie- tro, Marcello Scala, Maria Margherita Mancardi, Lino Nobili, Elisa- betta Amadori, Thea Giacomini, Francesca Bisulli, Tommaso Pippucci, Laura Licchetta, Raffaella Minardi, Paolo Tinuper, Lor- enzo Muccioli, Barbara Mostacci, Antonio Gambardella, Angelo Labate, Grazia Annesi, Lorella Manna, Monica Gagliardi, Elena Parrini, Davide Mei, Annalisa Vetro, Claudia Bianchini, Martino Montomoli, Viola Doccini, Carmen Barba, Shinichi Hirose, At- sushi Ishii, Toshimitsu Suzuki, Yushi Inoue, Kazuhiro Yamakawa, Ahmad Beydoun, Wassim Nasreddine, Nathalie Khoueiry Zgheib, Birute Tumiene, Algirdas Utkus, Lynette G. Sadleir, Chontelle King, S. Hande Caglayan, Mutluay Arslan, Zuhal Yap?c?, P?nar To- paloglu, Bulent Kara, Uluc Yis, Dilsad Turkdogan, Asl? Gun- dogdu-Eken, Nerses Bebek, Meng-Han Tsai, Chen-Jui Ho, Chih- Hsiang Lin, Kuang-Lin Lin, I-Jun Chou, Annapurna Poduri, Beth R. Shiedley, Catherine Shain, Jeffrey L. Noebels, Alicia Goldman, Robyn M. Busch, Lara Jehi, Imad M. Najm, Lisa Ferguson, Jean Khoury, Tracy A. Glauser, Peggy O. Clark, Russell J. Buono, Thomas N. Ferraro, Michael R. Sperling, Warren Lo, Michael Privitera, Jac- queline A. French, Steven Schachter, Ruben I. Kuzniecky, Orrin Devinsky, Manu Hegde, David A. Greenberg, Colin A. Ellis, Ethan Goldberg, Katherine L. Helbig, Mahgenn Cosico, Priya Vaidis- waran, Eryn Fitch, Samuel F. Berkovic, Holger Lerche, Daniel H. Lowenstein, David B. Goldstein., Motelow J.E., Povysil G., Dhindsa R.S., Stanley K.E., Allen A.S., Feng Y.-C.A., Howrigan D.P., Abbott L.E., Tashman K., Cerrato F., Cusick C., Singh T., Heyne H., Byrnes A.E., Churchhouse C., Watts N., Solomonson M., Lal D., Gupta N., Neale B.M., Cavalleri G.L., Cossette P., Cotsapas C., De Jonghe P., Dixon-Salazar T., Guerrini R., Hakonarson H., Heinzen E.L., Helbig I., Kwan P., Marson A.G., Petrovski S., Kamalakaran S., Sisodiya S.M., Stewart R., Weckhuysen S., Depondt C., Dlugos D.J., Scheffer I.E., Striano P., Freyer C., Krause R., May P., McKenna K., Regan B.M., Bennett C.A., Leu C., Leech S.L., O'Brien T.J., Todaro M., Stamberger H., Andrade D.M., Ali Q.Z., Sadoway T.R., Krestel H., Schaller A., Papacostas S.S., Kousiappa I., Tanteles G.A., Christou Y., Sterbova K., Vlckova M., Sedlackova L., Lassuthova P., Klein K.M., Rosenow F., Reif P.S., Knake S., Neubauer B.A., Zimprich F., Feucht M., Reinthaler E.M., Kunz W.S., Zsurka G., Surges R., Baumgartner T., von Wrede R., Pendziwiat M., Muhle H., Rademacher A., van Baalen A., von Spiczak S., Stephani U., Afawi Z., Korczyn A.D., Kanaan M., Canavati C., Kurlemann G., Muller-Schluter K., Kluger G., Hausler M., Blatt I., Lemke J.R., Krey I., Weber Y.G., Wolking S., Becker F., Lauxmann S., Bosselmann C., Kegele J., Hengsbach C., Rau S., Steinhoff B.J., Schulze-Bonhage A., Borggrafe I., Schankin C.J., Schubert-Bast S., Schreiber H., Mayer T., Korinthenberg R., Brockmann K., Wolff M., Dennig D., Madeleyn R., Kalviainen R., Saarela A., Timonen O., Linnankivi T., Lehesjoki A.-E., Rheims S., Lesca G., Ryvlin P., Maillard L., Valton L., Derambure P., Bartolomei F., Hirsch E., Michel V., Chassoux F., Rees M.I., Chung S.-K., Pickrell W.O., Powell R., Baker M.D., Fonferko-Shadrach B., Lawthom C., Anderson J., Schneider N., Balestrini S., Zagaglia S., Braatz V., Johnson M.R., Auce P., Sills G.J., Baum L.W., Sham P.C., Cherny S.S., Lui C.H.T., Delanty N., Doherty C.P., Shukralla A., El-Naggar H., Widdess-Walsh P., Barisic N., Canafoglia L., Franceschetti S., Castellotti B., Granata T., Ragona F., Zara F., Iacomino M., Riva A., Madia F., Vari M.S., Salpietro V., Scala M., Mancardi M.M., Nobili L., Amadori E., Giacomini T., Bisulli F., Pippucci T., Licchetta L., Minardi R., Tinuper P., Muccioli L., Mostacci B., Gambardella A., Labate A., Annesi G., Manna L., Gagliardi M., Parrini E., Mei D., Vetro A., Bianchini C., Montomoli M., Doccini V., Barba C., Hirose S., Ishii A., Suzuki T., Inoue Y., Yamakawa K., Beydoun A., Nasreddine W., Khoueiry Zgheib N., Tumiene B., Utkus A., Sadleir L.G., King C., Caglayan S.H., Arslan M., Yapici Z., Topaloglu P., Kara B., Yis U., Turkdogan D., Gundogdu-Eken A., Bebek N., Tsai M.-H., Ho C.-J., Lin C.-H., Lin K.-L., Chou I.-J., Poduri A., Shiedley B.R., Shain C., Noebels J.L., Goldman A., Busch R.M., Jehi L., Najm I.M., Ferguson L., Khoury J., Glauser T.A., Clark P.O., Buono R.J., Ferraro T.N., Sperling M.R., Lo W., Privitera M., French J.A., Schachter S., Kuzniecky R.I., Devinsky O., Hegde M., Greenberg D.A., Ellis C.A., Goldberg E., Helbig K.L., Cosico M., Vaidiswaran P., Fitch E., Berkovic S.F., Lerche H., Lowenstein D.H., Goldstein D.B., Epi25 Collaborative, Institut de Neurosciences des Systèmes (INS), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, focal epilepsy, Whole Exome Sequencing, Cohort Studies, Epilepsy, 0302 clinical medicine, Genetic Marker, Missense mutation, Exome, whole-exome sequencing, generalized epilepsy, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Exome sequencing, seizures, Genetics, ClinVar, Phenotype, epileptic encephalopathy, Epi25, intolerance, Case-Control Studie, Human, Genetic Markers, seizure, Disease Association, Biology, Article, 03 medical and health sciences, Exome Sequencing, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Generalized epilepsy, Gene, Louvain, [SCCO.NEUR]Cognitive science/Neuroscience, Correction, Genetic Variation, medicine.disease, epilepsy, Human genetics, 030104 developmental biology, Case-Control Studies, Human medicine, Cohort Studie, Genetic generalized epilepsy, 030217 neurology & neurosurgery
Abstract

Summary Both mild and severe epilepsies are influenced by variants in the same genes, yet an explanation for the resulting phenotypic variation is unknown. As part of the ongoing Epi25 Collaboration, we performed a whole-exome sequencing analysis of 13,487 epilepsy-affected individuals and 15,678 control individuals. While prior Epi25 studies focused on gene-based collapsing analyses, we asked how the pattern of variation within genes differs by epilepsy type. Specifically, we compared the genetic architectures of severe developmental and epileptic encephalopathies (DEEs) and two generally less severe epilepsies, genetic generalized epilepsy and non-acquired focal epilepsy (NAFE). Our gene-based rare variant collapsing analysis used geographic ancestry-based clustering that included broader ancestries than previously possible and revealed novel associations. Using the missense intolerance ratio (MTR), we found that variants in DEE-affected individuals are in significantly more intolerant genic sub-regions than those in NAFE-affected individuals. Only previously reported pathogenic variants absent in available genomic datasets showed a significant burden in epilepsy-affected individuals compared with control individuals, and the ultra-rare pathogenic variants associated with DEE were located in more intolerant genic sub-regions than variants associated with non-DEE epilepsies. MTR filtering improved the yield of ultra-rare pathogenic variants in affected individuals compared with control individuals. Finally, analysis of variants in genes without a disease association revealed a significant burden of loss-of-function variants in the genes most intolerant to such variation, indicating additional epilepsy-risk genes yet to be discovered. Taken together, our study suggests that genic and sub-genic intolerance are critical characteristics for interpreting the effects of variation in genes that influence epilepsy.

Published
2021
Full Text
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31. Experiences of VA vocational and education training and assistance services: Facilitators and barriers reported by veterans with disabilities

Author

Megan Shepherd-Banigan, Nina R. Sperber, Terri K. Pogoda, Courtney Harold Van Houtven, and Kevin McKenna

Subjects
Medical education, business.industry, Rehabilitation, MEDLINE, Rehabilitation, Vocational, PsycINFO, Health Professions (miscellaneous), humanities, United States, Article, Psychiatry and Mental health, United States Department of Veterans Affairs, Vocational education, Employment, Supported, Health care, Humans, Disabled Persons, Vocational rehabilitation, business, Psychology, Everyday life, Veterans Affairs, health care economics and organizations, Supported employment, Veterans
Abstract

Objective To understand the experiences of veterans with disabilities and caregiving needs who use Department of Veterans Affairs (VA) vocational and education services, including Supported Employment, the Post-9/11 GI Bill, and Vocational Rehabilitation and Employment. Method We conducted 26 joint semistructured interviews with post-9/11 veterans who had used at least one of three vocational and education services, and their family members who were enrolled in a VA Caregiver Support Program. Results VA vocational and education services helped veterans with disabilities transition from the military into civilian life by providing skills and incremental exposure to engaging in everyday life tasks. Veteran motivation, caregiver support, and engaged staff at VA and academic institutions were key drivers of veteran success. Veterans who experienced challenges cited the following barriers: health problems, concerns about benefits loss if they became employed, and VA and academic programs that did not accommodate the needs of nontraditional veteran learners. Conclusions and implications for practice There is a need to bolster VA vocational and educational services for veterans with disabilities in several domains, including modifying the roles of frontline staff and increasing communication between vocational counselors and health care teams to better accommodate the veteran's health-related limitations. Providing a vocational rehabilitation navigator to help veterans identify opportunities within VA and work/educational settings that are a good match for the veteran's goals and abilities could also be beneficial across vocational and educational services. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Published
2020

32. HORROR SHOW.

Author

Kevin McKenna

Abstract

ABERDEEN manager Jimmy Thelin insists he takes full responsibility for his side's failings following yesterday's calamitous defeat to St Mirren, as the dismal Dons' wretched Premiership winless run was extended to 13 games. [ABSTRACT FROM PUBLISHER]

Published
2025

33. NO CASE FOR THE DEFENCE OF THESE ROPEY REDS.

Author

Kevin McKenna

Abstract

FEW of an Aberdeen persuasion were getting too carried away in the wake of the Scottish Cup victory at Elgin City last weekend which ended their side's recent wretched 12-game winless sequence. By this stage, they know better than that. [ABSTRACT FROM PUBLISHER]

Published
2025

38. Clement sure Ibrox squad can cope with hectic schedule.

Author

KEVIN McKENNA

Abstract

RANGERS boss Philippe Clement insists his squad have the necessary strength in depth to handle their gruelling upcoming schedule. His team will face no fewer than 11 games between now and the end of January, starting with a tricky Boxing Day trip to St Mirren. [ABSTRACT FROM PUBLISHER]

Published
2024

39. BABY STEPS.

Author

KEVIN McKENNA

Abstract

RANGERS Cerny 46 1 [ABSTRACT FROM PUBLISHER]

Published
2024

42. Disaster Caregiving: Caregivers Negotiating Storms and COVID-19 for Veterans and Non-Veterans on the Gulf Coast

Author

Nathan Boucher, Kevin McKenna, Carrie Dombeck, Amy Clark, Ke Wang, Jennifer Olson, and Megan Shepherd-Banigan

Subjects
Abstracts, Health (social science), Life-span and Life-course Studies, AcademicSubjects/SOC02600, Health Professions (miscellaneous), Session 4080 (Symposium), humanities
Abstract

Natural disasters and COVID-19 likely add complexity to caregiving efforts, yet little is known about these effects. We will discuss our findings exploring additional needs and challenges experienced by caregivers during hurricanes, floods, and COVID focused on US Gulf Coast states. We interviewed caregivers of both Veterans (n=13) and non-Veterans (n=11). The presentation will include an overview of 1) types of resources needed or used related to storms and to COVID, including social support and access to information for both emergency planning and recovery; 2) caregiver experience before, during, and after the disaster including psychological effects on caregivers and addressing special health needs; 3) comparisons of challenges during storms versus COVID including emotional impact and access to health and specialty care; and 4) additional resources used by caregivers of Veterans. We will also address how these data are informing national caregiver support programs.

Published
2021

43. How to Drag Race

Author

Kevin McKenna and Kevin McKenna

Subjects
Drag racing
Abstract

The photos in this edition are black and white.From race registration to the finish line and everything in between, How to Drag Race explains all the steps for successful drag racing, so the aspiring drag racer can easily setup his or her car, launch off the line, and quickly run at every racetrack. It offers the first comprehensive description of every aspect of drag racing, including car set up, driving techniques, class information, and getting active in racing at the local level. Author Kevin McKenna, editor at National DRAGSTER, NHRA's weekly news magazine, uses 300 color photos to show you what to expect your first time out, how to set your street car or race car up for consistency and speed, and driving techniques for racers at all levels. He discusses tires, safety equipment, driving aids, such as line-locks and delay boxes, choosing a class, and advanced racer math. Special sections detail how to maximize your setup and strategy bracket racing success. If you have ever thought it would be fun to give drag racing a try, this book is for you. If you have ever thought it would be fun to give drag racing a try, this book is for you.

Published
2020

44. How Many Focus Groups Are Enough? Building an Evidence Base for Nonprobability Sample Sizes

Author

Greg Guest, Kevin McKenna, and Emily Namey

Subjects
Research design, Evidence-based practice, Research methodology, Focus group, Data science, Nonprobability sampling, 03 medical and health sciences, 0302 clinical medicine, Empirical research, Sample size determination, Anthropology, 030212 general & internal medicine, Health behavior, Psychology, Social psychology, 030217 neurology & neurosurgery
Abstract

Few empirical studies exist to guide researchers in determining the number of focus groups necessary for a research study. The analyses described here provide foundational evidence to help researchers in this regard. We conducted a thematic analysis of 40 focus groups on health-seeking behaviors of African American men in Durham, North Carolina. Our analyses revealed that more than 80% of all themes were discoverable within two to three focus groups, and 90% were discoverable within three to six focus groups. Three focus groups were also enough to identify all of the most prevalent themes within the data set. These empirically based findings suggest focus group sample sizes that differ from many of the “rule of thumb” recommendations in the existing literature. We discuss the relative generalizability of our findings to other study contexts, and we highlight some methodological questions about adequate sample sizes for focus group research.

Published
2016
Full Text
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45. Evaluating Bang for the Buck

Author

Emily Namey, Kevin McKenna, Greg Guest, and Mario Chen

Subjects
Health (social science), Data collection, Sociology and Political Science, Social Psychology, Cost effectiveness, 030503 health policy & services, Strategy and Management, Qualitative property, Focus group, Education, Data set, 03 medical and health sciences, 0302 clinical medicine, Statistics, 030212 general & internal medicine, Business and International Management, Thematic analysis, 0305 other medical science, Psychology, Social psychology, Coding (social sciences), Qualitative research
Abstract

Evaluators often use qualitative research methods, yet there is little evidence on the comparative cost-effectiveness of the two most commonly employed qualitative methods—in-depth interviews (IDIs) and focus groups (FGs). We performed an inductive thematic analysis of data from 40 IDIs and 40 FGs on the health-seeking behaviors of African American men ( N = 350) in Durham, North Carolina. We used a bootstrap simulation to generate 10,000 random samples from each data set and calculated the number of data collection events necessary to reach different levels of thematic saturation. The median number of data collection events required to reach 80% and 90% saturation was 8 and 16, respectively, for IDIs and 3 and 5 for FGs. Interviews took longer but were more cost-effective at both levels. At the median, IDIs cost 20–36% less to reach thematic saturation. Evaluators can consider these empirically based cost-effectiveness data when selecting a qualitative data collection method.

Published
2016
Full Text
View/download PDF

48. No more slip-ups, demands Barron.

Author

Kevin McKenna

Abstract

CONNOR BARRON has urged his Rangers team-mates to make sure Thursday's blistering four-goal demolition of Steaua Bucharest isn't an outlier as they look to get their faltering domestic campaign back on track. [ABSTRACT FROM PUBLISHER]

Published
2024

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