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DESCRIPTION: The American College of Physicians (ACP) developed this clinical guideline to update recommendations on newer pharmacologic treatments of type 2 diabetes. This clinical guideline is based on the best available evidence for effectiveness, comparative benefits and harms, consideration of patients values and preferences, and costs. METHODS: This clinical guideline is based on a systematic review of the effectiveness and harms of newer pharmacologic treatments of type 2 diabetes, including glucagon-like peptide-1 (GLP-1) agonists, a GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and long-acting insulins, used either as monotherapy or in combination with other medications. The Clinical Guidelines Committee prioritized the following outcomes, which were evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach: all-cause mortality, major adverse cardiovascular events, myocardial infarction, stroke, hospitalization for congestive heart failure, progression of chronic kidney disease, serious adverse events, and severe hypoglycemia. Weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis and were not rated with GRADE. AUDIENCE AND PATIENT POPULATION: The audience for this clinical guideline is physicians and other clinicians. The population is nonpregnant adults with type 2 diabetes. RECOMMENDATION 1: ACP recommends adding a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control (strong recommendation; high-certainty evidence). • Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure. • Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke. RECOMMENDATION 2: ACP recommends against adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality (strong recommendation; high-certainty evidence).

DESCRIPTION: This guideline updates the 2017 American College of Physicians (ACP) recommendations on pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults. METHODS: The ACP Clinical Guidelines Committee based these recommendations on an updated systematic review of evidence and graded them using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. AUDIENCE AND PATIENT POPULATION: The audience for this guideline includes all clinicians. The patient population includes adults with primary osteoporosis or low bone mass. RECOMMENDATION 1A: ACP recommends that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis (strong recommendation; high-certainty evidence). RECOMMENDATION 1B: ACP suggests that clinicians use bisphosphonates for initial pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis (conditional recommendation; low-certainty evidence). RECOMMENDATION 2A: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in postmenopausal females diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; moderate-certainty evidence). RECOMMENDATION 2B: ACP suggests that clinicians use the RANK ligand inhibitor (denosumab) as a second-line pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates (conditional recommendation; low-certainty evidence). RECOMMENDATION 3: ACP suggests that clinicians use the sclerostin inhibitor (romosozumab, moderate-certainty evidence) or recombinant PTH (teriparatide, low-certainty evidence), followed by a bisphosphonate, to reduce the risk of fractures only in females with primary osteoporosis with very high risk of fracture (conditional recommendation). RECOMMENDATION 4: ACP suggests that clinicians take an individualized approach regarding whether to start pharmacologic treatment with a bisphosphonate in females over the age of 65 with low bone mass (osteopenia) to reduce the risk of fractures (conditional recommendation; low-certainty evidence).

Epilepsy genetics is a rapidly developing field, in which novel disease-associated genes, novel mechanisms associated with epilepsy, and precision medicine approaches are continuously being identified. In the past decade, advances in genomic knowledge and analysis platforms have begun to make clinical genetic testing accessible for, in principle, people of all ages with epilepsy. For this reason, the Genetics Commission of the International League Against Epilepsy (ILAE) presents this update on clinical genetic testing practice, including current techniques, indications, yield of genetic testing, recommendations for pre- and post-test counseling, and follow-up after genetic testing is completed. We acknowledge that the resources vary across different settings but highlight that genetic diagnostic testing for epilepsy should be prioritized when the likelihood of an informative finding is high. Results of genetic testing, in particular the identification of causative genetic variants, are likely to improve individual care. We emphasize the importance of genetic testing for individuals with epilepsy as we enter the era of precision therapy.

BACKGROUND: Mental health disorders in the context of long-term conditions in children and young people are currently overlooked and undertreated. Evidence-based psychological treatments for common childhood mental health disorders (anxiety, depression and disruptive behaviour disorders) have not been systematically evaluated in young people with epilepsy despite their high prevalence in this population. The aim of this multi-site randomised controlled trial is to determine the clinical and cost-effectiveness of adding a modular psychological intervention to usual care for the mental health disorders in comparison to assessment-enhanced usual care alone. METHODS: In total, 334 participants aged 3-18 years attending epilepsy services will be screened for mental health disorders with the Strengths and Difficulties Questionnaire (SDQ) and the diagnostic Development and Wellbeing Assessment (DAWBA). Those identified as having a mental health disorder and consenting to the trial will be randomised to either receive up to 22 sessions of the modular psychological intervention (MATCH-ADTC) delivered over the telephone over 6 months by non-mental health professionals in addition to usual care or to assessment-enhanced usual care alone. Outcomes will be measured at baseline, 6 months and 12 months post-randomisation. It is hypothesised that MATCH-ADTC plus usual care will be superior to assessment-enhanced usual care in improving emotional and behavioural symptoms. The primary outcome is the SDQ reported by parents at 6 months. Secondary outcomes include parent-reported mental health measures such as the Revised Childrens Anxiety and Depression Scale, quality of life measures such as the Paediatric Quality of Life Inventory and physical health measures such as the Hague Seizure Severity Scale. Outcome assessors will be blinded to group assignment. Qualitative process evaluations and a health economic evaluation will also be completed. DISCUSSION: This trial aims to determine whether a systematic and integrated approach to the identification and treatment of mental health disorders in children and young people with epilepsy is clinically and cost-effective. The findings will contribute to policies and practice with regard to addressing mental health needs in children and young people with other long-term conditions. TRIAL REGISTRATION: ISRCTN ISRCTN57823197 . Registered on 25 February 2019.

Introduction: The prevalence of epilepsy in sub-Saharan Africa varies considerably, and the exact estimate for Ghana remains unclear, particularly in peri-urban areas where data are scarce. More community-based studies are required to understand better the actual burden of epilepsy in these areas and the difficulties in accessing healthcare. Objective: To adapt and validate a household survey epilepsy-screening instrument in Shai-Osudoku and Ningo-Prampram District of Greater Accra Region, Ghana. Methods: We developed a 17-item epilepsy screening instrument by modifying previously validated English language questionnaires. We included questions that could identify convulsive and non-convulsive seizures. Language experts forward- and back-translated the questionnaires into the two languages: Asante Twi and Dangme. Cases were people with confirmed epilepsy attending healthcare facilities where these languages are used. Controls were unaffected relatives of cases or people attending the same healthcare facilities for other medical conditions. We matched cases and controls for geographical location and ethnicity. An affirmative response to one of the seventeen questions by a participant was deemed a positive screen. The questionnaires were divided into two stages. The first stage consisted of broader, more general questions aimed at identifying potential cases of epilepsy. The second stage involved a more detailed and focused set of questions administered to those who screened positive in the first stage. Results: One hundred and forty Dangme speakers (70 cases and 70 controls) and 100 Asante Twi speakers (50 cases and 50 controls) were recruited. The sensitivity and specificity for Dangme were: Stage 1, 100% and 80%, and Stage 2, 98.6% and 85.7%. The Dangme version reliably identified epilepsy with positive predictive values of 83.3% and 87.3% at stages 1 and 2. The questionnaire excluded epilepsy with 100% and 98.4% negative predictive values. For the Asante Twi version, the sensitivity and specificity were 98% and 92% (95% at Stage 1, and for Stage 2, 96% and 94%. The Asante Twi questionnaire reliably specified epilepsy with positive predictive values of 92.5% and 94.1% at stages 1 and 2. It excluded epilepsy with negative predictive values of 97.9% and 95.9% for the two stages Conclusions: Our questionnaire is valid for the two languages and usable for community-based epilepsy surveys in Ghana. It can also be adapted for other resource-poor settings, although translation and iterative in-country testing will be needed to ensure its validity. [ABSTRACT FROM AUTHOR]

Ketogenic dietary therapies (KDTs) are established, effective nonpharmacologic treatments for intractable childhood epilepsy. For many years KDTs were implemented differently throughout the world due to lack of consistent protocols. In 2009, an expert consensus guideline for the management of children on KDT was published, focusing on topics of patient selection, pre-KDT counseling and evaluation, diet choice and attributes, implementation, supplementation, follow-up, side events, and KDT discontinuation. It has been helpful in outlining a state-of-the-art protocol, standardizing KDT for multicenter clinical trials, and identifying areas of controversy and uncertainty for future research. Now one decade later, the organizers and authors of this guideline present a revised version with additional authors, in order to include recent research, especially regarding other dietary treatments, clarifying indications for use, side effects during initiation and ongoing use, value of supplements, and methods of KDT discontinuation. In addition, authors completed a survey of their institution's practices, which was compared to responses from the original consensus survey, to show trends in management over the last 10 years.

Background and purposePrimary-progressive aphasia is a clinically and pathologically heterogeneous condition. Nonfluent, semantic, and logopenic are the currently recognized clinical variants. The recommendations for the classification of primary-progressive aphasia have advocated variant-specific patterns of atrophy. The aims of the present study were to evaluate the sensitivity and specificity of the proposed imaging criteria and to assess the intra- and interrater reporting agreements.Materials and methodsThe cohort comprised 51 patients with a root diagnosis of primary-progressive aphasia, 25 patients with typical Alzheimer disease, and 26 matched control participants. Group-level analysis (voxel-based morphometry) confirmed the proposed atrophy patterns for the 3 syndromes. The individual T1-weighted anatomic images were reported by 3 senior neuroradiologists.ResultsWe observed a dichotomized pattern of high sensitivity (92%) and specificity (93%) for the proposed atrophy pattern of semantic-variant primary-progressive aphasia and low sensitivity (21% for nonfluent-variant primary-progressive aphasia and 43% for logopenic-variant primary-progressive aphasia) but high specificity (91% for nonfluent-variant primary-progressive aphasia and 95% for logopenic-variant primary-progressive aphasia) in other primary-progressive aphasia variants and Alzheimer disease (sensitivity 43%, specificity 92%). MR imaging was least sensitive for the diagnosis of nonfluent-variant primary-progressive aphasia. Intrarater agreement analysis showed mean κ values above the widely accepted threshold of 0.6 (mean, 0.63 ± 0.16). Pair-wise interobserver agreement outcomes, however, were well below this threshold in 5 of the 6 possible interrater contrasts (mean, 0.41 ± 0.09).ConclusionsWhile the group-level results were in precise agreement with the recommendations, semantic-variant primary-progressive aphasia was the only subtype for which the proposed recommendations were both sensitive and specific at an individual level.

Fenfluramine (FFA), an antiseizure medication (ASM) with serotonergic and sigma‐1 receptor activity, is used to manage patients with developmental and epileptic encephalopathies (DEEs). It is approved in the US for treating seizures associated with Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS) in patients ≥2 years old and as add‐on therapy for seizures associated with DS and LGS in the EU, UK, and Japan in similarly aged patients. Consensus guidelines for treatment of DS have recommended FFA to be an early‐line ASM, and it has also shown efficacy in managing seizures associated with LGS. DS and LGS are DEEs associated with a range of seizure types, developmental impairments, and multiple comorbidities. Here we provide case vignettes describing 4 patients (3 DS and 1 LGS) aged 4–29 years old in whom up to 14 ASMs had previously failed, to illustrate real‐world practice issues encountered by neurologists. This review provides guidance on the use of FFA in the context of ASM polytherapy and drug–drug interactions (DDIs), behavioral issues, dose titration, and adverse events. Along with data from the clinical trial program, these case vignettes emphasize the low risk of DDIs, a generally well‐tolerated safety profile, and other seizure and nonseizure benefits (eg, improved cognition and sleep) associated with the use of FFA in DS or LGS. Plain Language Summary: Fenfluramine is used to treat seizures in individuals with Dravet syndrome and Lennox–Gastaut syndrome, but there are a range of issues that clinicians may face when treating patients. This review highlights four patients from the authors' everyday clinical work and offers guidance and practical considerations by neurologists with expertise in managing these complex conditions related to drug interactions, dosing, and side effects associated with fenfluramine. [ABSTRACT FROM AUTHOR]

BackgroundGuidelines recommend that surgery be considered in patients with drug-resistant epilepsy, yet delays to epilepsy surgery still exist. A Web-based, evidence-informed clinical decision tool (www.toolsforepilepsy.com) was developed to help physicians determine which patients are appropriate for an epilepsy surgery evaluation. We evaluated the usability and feasibility of the tool with the intended end users in order to improve implementation into practice.MethodsUsability testing was conducted with relevant end users. After the tool was modified based on usability results, another group of end users trialed the tool in their clinical practice. This latter group of end users then participated in focus groups and semi-structured interviews to address barriers and facilitators to tool implementation. Finally, a stakeholder meeting was held with domain experts and end users to discuss further changes to the tool and implementation strategies.ResultsSix overall themes were identified through usability testing, and an additional 11 themes were identified through the focus groups and interviews. The tool was modified based on these findings, which were then presented at the stakeholder meeting of experts and end users for further refinement. The findings were also used to guide discussions of potential implementation strategies at the meeting.ConclusionThis study provides guidance on how to improve the usability of clinical decision tools by engaging end users, experts, and other key stakeholders. The modifications to the tool should facilitate its implementation in clinical practice and ultimately enhance the quality of care persons with epilepsy receive.

Epilepsy was defined conceptually in 2005 as a disorder of the brain characterized by an enduring predisposition to generate epileptic seizures. This definition is usually practically applied as having two unprovoked seizures >24 h apart. The International League Against Epilepsy (ILAE) accepted recommendations of a task force altering the practical definition for special circumstances that do not meet the two unprovoked seizures criteria. The task force proposed that epilepsy be considered to be a disease of the brain defined by any of the following conditions: (1) At least two unprovoked (or reflex) seizures occurring >24 h apart; (2) one unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years; (3) diagnosis of an epilepsy syndrome. Epilepsy is considered to be resolved for individuals who either had an age-dependent epilepsy syndrome but are now past the applicable age or who have remained seizure-free for the last 10 years and off antiseizure medicines for at least the last 5 years. "Resolved" is not necessarily identical to the conventional view of "remission or "cure." Different practical definitions may be formed and used for various specific purposes. This revised definition of epilepsy brings the term in concordance with common use. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Epilepsy surgery is highly successful in achieving seizure freedom in carefully selected children with drug-resistant focal epilepsy. Advances in technology have aided presurgical evaluation and increased the number of possible candidates. Many of the tests employed are resource intense, and in specific cases they may be unhelpful or have adverse effects. Some standardization of the evaluation process is thus considered timely. Given the lack of class 1 or 2 evidence defining the relative utility of each test in specific clinicopathologic cohorts, a set of expert recommendations was attempted using consensus among members of the Pediatric Epilepsy Surgery Task Force of the International League Against Epilepsy (ILAE) Commissions of Pediatrics and Diagnostics These recommendations aim to limit fringe over or underutilization of use while retaining substantial flexibility in the use of various tests, in keeping with most standard practices at established pediatric epilepsy centers. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Objective: To investigate the repercussions of the war in Ukraine on people with epilepsy (PWE), focusing on access to health care, seizure control, quality of life (QoL), psychological distress, anxiety, and depression; and to identify the key factors influencing these measures. Methods: Consecutive PWE, ≥18 years of age, presenting to one of seven health centers across Ukraine were invited to complete a self‐administered survey in 2023. The survey gathered information on clinical and demographic aspects, geographic displacement, and access to care and medications. It also contained five valid questionnaires exploring psychological distress (Kessler‐10), QoL with the EuroQOL‐5D‐5L (EQ‐5D‐5L), depression with the Neurological Disorders in Epilepsy scale (NDDIE), anxiety with the Hospital Anxiety and Depression Scalae‐Anxiety (HADS‐A), and epilepsy severity with the Global Assessment of the Severity of Epilepsy scale (GASE). Multivariate linear regression models assessed the relationship between measures of mental health and QoL and their potential predictors. Ethical approval was obtained from the Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine, Ukraine. Results: Among 305 participants (mean age 38 years), 40% were female and 44% had to change residence because of the war. Seizures worsened during the war in 52% of those with active epilepsy and 42% of those with well‐controlled epilepsy. Difficulties accessing health care and anti‐seizure medications occurred in 25% and 34% of PWE, respectively, and was worse among those who were displaced. According to the mental health instruments, 46% suffered psychological distress, 62% experienced anxiety, 50% were depressed, and 59% rated their epilepsy as somewhat severe or worse. Statistically significant predictors of psychological distress, anxiety, and depression included female gender, more severe epilepsy, increased seizures during the war, and requiring mental health support. Significance: The war significantly disrupted access to health care and availability of medication in PWE, who suffer from significant anxiety, depression, and psychological distress. We identify high‐risk factors that can guide resource allocation for prevention and treatment. [ABSTRACT FROM AUTHOR]

Developmental and epileptic encephalopathies (DEEs) are characterized by pharmacoresistant seizures and developmental delay. Patients with DEEs experience multiple seizure types, including tonic–clonic seizures (TCS) that can be generalized tonic–clonic (GTCS) or focal evolving to bilateral tonic–clonic (FBTCS). Fenfluramine (FFA) has demonstrated efficacy in reduction of TCS in patients with Dravet syndrome (DS), Lennox–Gastaut syndrome (LGS), and other DEEs. Using the PRISMA‐ScR (Preferred Reporting Items for Systematic Review and Meta‐Analyses extension for Scoping Review) guidelines, we performed a scoping review to describe changes in TCS in patients treated with FFA. A comprehensive search of five literature databases was conducted up to February 14, 2023. Studies were included if they reported change in GTCS or TCS (but not FBTCS) after treatment with FFA in patients with DEEs. Duplicate patients and studies with unclear efficacy data were excluded. Fourteen of 422 studies met the eligibility criteria. Data extracted and evaluated by expert clinicians identified 421 unique patients with DS (in nine studies), CDKL5 deficiency disorder, SCN8A‐related disorder, LGS, SCN1B‐related disorder, and other DEEs. The median percent reduction in GTCS or TCS from baseline was available in 10 studies (n = 328) and ranged from 47.2% to 100%. Following FFA treatment, 10 studies (n = 144) reported ≥50% reduction in GTCS or TCS from baseline in 72% of patients; in nine of those (n = 112), 54% and 29% of patients achieved ≥75% and 100% reduction in GTCS or TCS from baseline, respectively. Overall, this analysis highlighted improvements in GTCS or TCS frequency when patients were treated with FFA regardless of the DEE evaluated. Future studies may confirm the impact of FFA on TCS reduction and on decreased premature mortality risk (including sudden unexpected death in epilepsy), improvement in comorbidities and everyday executive function, decreased health care costs, and improvement in quality of life. [ABSTRACT FROM AUTHOR]

The implementation and potential of ketogenic dietary therapies (KDTs) have changed over time. The organization of KDT services, the availability of multidisciplinary teams, resources and support for patients and families still vary widely around the world. This diversity is reflected by a lack of consistency in reported outcomes, optimization of using KDT and KDT compliance. To highlight the unmet needs for KDT services, the ERN EpiCARE Ketogenic Dietary Therapy Special Interest Group (KDT SIG) conducted an online survey on KDT implementation and utilization, addressing the following topics: Use and completeness of guidelines and protocols; assessment of compliance and outcome parameters, sustainability and inclusivity in daily life. Consistently reported unmet needs included the lack of psychological support and resources to measure and improve adherence to KDT, the lack of inclusion strategies, and shared guidelines and protocols adapting to specific needs. Future interventions should focus primarily on educational and informative measures together with creation of shared protocols for complex care. Plain Language Summary: This study provides the results of a survey compiled by clinicians and patients representatives belonging to ERN Epicare, designed to unravel unmet needs from both patients' and healthcare practitioners' perspectives during ketogenic dietary therapies (KDT) provision. Importantly, results show the need to create new shared protocols and guidelines meant for KDT use in complex care situations and to develop future strategies initiatives to support patients improving their social inclusivity. [ABSTRACT FROM AUTHOR]

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy, and their representatives to develop minimum sets of standardized outcomes and outcome measurement methods for clinical practice. Using modified Delphi consensus methods with consecutive rounds of online voting over 12 months, a core set of outcomes and corresponding measurement tool packages to capture the outcomes were identified for infants, children, and adolescents with epilepsy. Consensus methods identified 20 core outcomes. In addition to the outcomes identified for the ICHOM Epilepsy adult standard set, behavioral, motor, and cognitive/language development outcomes were voted as essential for all infants and children with epilepsy. The proposed set of outcomes and measurement methods will facilitate the implementation of the use of patient‐centered outcomes in daily practice. [ABSTRACT FROM AUTHOR]