Clinical Characteristics and Treatment Experience of Individuals with SCN8A Developmental and Epileptic Encephalopathy (SCN8A-DEE): Findings from an Online Caregiver Survey

ABSTRACT Purpose: SCN8A developmental epileptic encephalopathy (SCN8A-DEE) is a rare and severe genetic epilepsy syndrome characterized by early-onset developmental delay, cognitive impairment, and intractable seizures. Variants in the SCN8A gene are associated with a broad phenotypic spectrum and variable disease severity. A caregiver survey, solicited by the advocacy group The Cute Syndrome Foundation (TCSF), was conducted to gather information on the demographics/disease presentation, seizure history, and treatment of patients with SCN8Arelated epilepsies. Methods: A 36-question online survey was developed to obtain de-identified data from caregivers of children with SCN8A-related epilepsy. The survey included questions on genetic diagnosis, disease manifestations/comorbidities, seizure severity/type, current/prior use of antiseizure medicines (ASMs), and best/worst treatments per caregiver perception. Results: In total, 116 survey responses (87 USA, 12 Canada, 12 UK, 5 Australia) were included in the quantitative analysis. Generalized tonic/clonic was the most common seizure type at onset and time of survey; absence and partial/focal seizures were also common. Most patients (77%) were currently taking ≥2 ASMs; 50% had previously tried and stopped ≥4 ASMs. Sodium channel blockers (oxcarbazepine, phenytoin, lamotrigine) provided the best subjective seizure control and quality of life. Conclusion: The SCN8A-DEE patient population is heterogeneous and difficult to treat, with high seizure burden and multiple comorbidities. The high proportion of patients who previously tried and stopped ASMs indicates a large unmet treatment need. Further collaboration between families, caregivers, patient advocates, clinicians, researchers, and industry can increase awareness and understanding of SCN8A-related epilepsies, improve clinical trial design, and potentially improve patient outcomes.

Epidemiology and treatment patterns of idiopathic multicentric Castleman disease in the era of IL-6 directed therapy

The epidemiology of HHV-8-negative/idiopathic multicentric Castleman disease (iMCD) remains incompletely understood. Prior epidemiologic studies of CD and iMCD have been hampered by difficulties in accurate case ascertainment due to lack of uniform diagnostic criteria and a disease-specific International Classification of Diseases (ICD) code. In this study, we provide reliable estimates of CD and iMCD in the US using a novel claims-based algorithm that includes CD specific ICD-10 diagnosis code (D47.Z2) supported by presence of ≥2 claims codes corresponding to the minor criteria from the international evidence-based diagnostic criteria for iMCD. We additionally analyzed the treatment classes and patterns in the clinical course of iMCD patients. Using an administrative claims database of 30.7 million individuals enrolled between January 1, 2017 and December 31, 2018, we identified 254 iMCD patients with an estimated annual incidence and prevalence of 3.4 (95% CI, 1.4 - 9.2) and 6.9 (95% CI, 3.7 - 13.3) cases per million, respectively. Among iMCD patients, 39% received corticosteroid monotherapy, 33.1% received no iMCD-directed treatment, and 9.8% received IL-6 targeted therapy with tocilizumab or siltuximab. Siltuximab, which is the only FDA-approved treatment and established first-line treatment recommendation, was used in only 8.7% of iMCD patients. This study provides the most up to date understanding of the iMCD disease burden in the US and identifies a major unmet treatment need for IL-6 directed therapy in this vulnerable cohort.

Isatuximab for relapsed/refractory multiple myeloma: review of key subgroup analyses from the Phase III ICARIA-MM study

In the Phase III ICARIA-MM study (NCT02990338), the addition of the anti-CD38 monoclonal antibody isatuximab to pomalidomide and dexamethasone led to increased progression-free survival and improved response rates in patients with relapsed/refractory multiple myeloma. There is an unmet treatment need, particularly among patients with poor prognoses, including those with high-risk cytogenetics, those who have renal impairment, those who are elderly and those who are refractory to prior lines of treatment. In this review, the subgroup analyses from the ICARIA-MM study, representing subpopulations with poor prognostic factors, are discussed. Overall, the addition of isatuximab to pomalidomide and dexamethasone improved progression-free survival and disease response rates across different subgroups, regardless of prognostic factor.

Sustainability planning in the US response to the opioid crisis: An examination using expert and text mining approaches

Between January 2016 and June 2020, the Substance Abuse and Mental Health Services Administration rapidly distributed $7.5 billion in response to the U.S. opioid crisis. These funds are designed to increase access to medications for addiction treatment, reduce unmet treatment need, reduce overdose death rates, and provide and sustain effective prevention, treatment and recovery activities. It is unclear whether or not the services developed using these funds will be sustained beyond the start-up period. Based on 34 (64%) State Opioid Response (SOR) applications, we assessed the states’ sustainability plans focusing on potential funding sources, policies, and quality monitoring. We found variable commitment to sustainability across response plans with less than half the states adequately describing sustainability plans. States with higher proportions of opioid prescribing, opioid misuse, and poverty had somewhat higher scores on sustainment. A text mining/machine learning approach automatically rated sustainability in SOR applications with an 82% accuracy compared to human ratings. Because life saving evidence-based programs and services may be lost, intentional commitment to sustainment beyond the bolus of start-up funding is essential.

Mobile-Assisted Cognitive Behavioral Therapy for Negative Symptoms: Open Single-Arm Trial With Schizophrenia Patients

Background Negative symptoms are an important unmet treatment need for schizophrenia. This study is a preliminary, open, single-arm trial of a novel hybrid intervention called mobile-assisted cognitive behavioral therapy for negative symptoms (mCBTn). Objective The primary aim was to test whether mCBTn was feasible and could reduce severity of the target mechanism, defeatist performance attitudes, which are associated with experiential negative symptoms and poor functioning in schizophrenia. Methods Participants with schizophrenia or schizoaffective disorder (N=31) who met prospective criteria for persistent negative symptoms were enrolled. The blended intervention combines weekly in-person group therapy with a smartphone app called CBT2go. The app extended therapy group skills, including recovery goal setting, thought challenging, scheduling of pleasurable activities and social interactions, and pleasure-savoring interventions to modify defeatist attitudes and improve experiential negative symptoms. Results Retention was excellent (87% at 18 weeks), and severity of defeatist attitudes and experiential negative symptoms declined significantly in the mCBTn intervention with large effect sizes. Conclusions The findings suggest that mCBTn is a feasible and potentially effective treatment for experiential negative symptoms, if confirmed in a larger randomized controlled trial. The findings also provide support for the defeatist attitude model of experiential negative symptoms and suggest that blended technology-supported interventions such as mCBTn can strengthen and shorten intensive psychosocial interventions for schizophrenia. Trial Registration ClinicalTrials.gov NCT03179696; https://clinicaltrials.gov/ct2/show/NCT03179696

Mobile-Assisted Cognitive Behavioral Therapy for Negative Symptoms: Open Single-Arm Trial With Schizophrenia Patients (Preprint)

BACKGROUND Negative symptoms are an important unmet treatment need for schizophrenia. This study is a preliminary, open, single-arm trial of a novel hybrid intervention called mobile-assisted cognitive behavioral therapy for negative symptoms (mCBTn). OBJECTIVE The primary aim was to test whether mCBTn was feasible and could reduce severity of the target mechanism, defeatist performance attitudes, which are associated with experiential negative symptoms and poor functioning in schizophrenia. METHODS Participants with schizophrenia or schizoaffective disorder (N=31) who met prospective criteria for persistent negative symptoms were enrolled. The blended intervention combines weekly in-person group therapy with a smartphone app called CBT2go. The app extended therapy group skills, including recovery goal setting, thought challenging, scheduling of pleasurable activities and social interactions, and pleasure-savoring interventions to modify defeatist attitudes and improve experiential negative symptoms. RESULTS Retention was excellent (87% at 18 weeks), and severity of defeatist attitudes and experiential negative symptoms declined significantly in the mCBTn intervention with large effect sizes. CONCLUSIONS The findings suggest that mCBTn is a feasible and potentially effective treatment for experiential negative symptoms, if confirmed in a larger randomized controlled trial. The findings also provide support for the defeatist attitude model of experiential negative symptoms and suggest that blended technology-supported interventions such as mCBTn can strengthen and shorten intensive psychosocial interventions for schizophrenia. CLINICALTRIAL ClinicalTrials.gov NCT03179696; https://clinicaltrials.gov/ct2/show/NCT03179696

Hepatitis C Virus (HCV) Care Continuum Outcomes and HCV Community Viral Loads Among Patients in an Opioid Treatment Program

Background Hepatitis C virus (HCV) remains endemic among people who use drugs (PWUD). Measures of HCV community viral load (CVL) and HCV care continuum outcomes may be valuable for ascertaining unmet treatment need and for HCV surveillance and control. Methods Data from patients in an opioid treatment program during 2013–2016 were used to (1) identify proportions of antibody and viral load (VL) tested, linked-to-care, and treated, in 2013–2014 and 2015–2016, and pre- and postimplementation of qualitative reflex VL testing; (2) calculate engaged-in-care HCV CVL and “documented” and “estimated” unmet treatment need; and (3) examine factors associated with linkage-to-HCV-care. Results Among 11 267 patients, proportions of HCV antibody tested (52.5% in 2013–2014 vs 73.3% in 2015–2016), linked-to-HCV-care (15.7% vs 51.8%), and treated (12.0% vs 44.7%) all increased significantly. Hispanic ethnicity was associated with less linkage-to-care, and Manhattan residence was associated with improved linkage-to-care. The overall engaged-in-care HCV CVL was 4 351 079 copies/mL (standard deviation = 7 149 888); local HCV CVLs varied by subgroup and geography. Documented and estimated unmet treatment need decreased but remained high. Conclusions After qualitative reflex VL testing was implemented, care continuum outcomes improved, but gaps remained. High rates of unmet treatment need suggest that control of the HCV epidemic among PWUD will require expansion of HCV treatment coverage.

Gout Activity Score has predictive validity and is sensitive to change: results from the Nottingham Gout Treatment Trial (Phase II)

Objectives To examine the predictive validity of the Gout Activity Score (GAS), its correlation with the Gout Impact Scale (GIS) and their sensitivity to change. Methods Data from a clinical trial in which participants with one or more gout flares in the previous year were recruited from primary care and randomized to nurse-led or continuing usual care were used in this study. GAS and GIS were calculated as described, with higher scores indicating worse disease activity and quality of life, respectively. The correlation between GAS and GIS was examined using Spearman’s correlation. Standardized response means (SRMs) were calculated to assess sensitivity to change. The association between GAS at baseline and the number of flares in the next 12 months was evaluated using Poisson regression. Data analyses were performed using STATA version 14, with P-values <0.05 being statistically significant. Results There was low positive correlation between GAS and gout concern overall and unmet treatment need subscales of GIS (r = 0.34–0.45). Female sex associated independently with fewer gout flares, while increasing GAS, BMI and age associated independently with frequent flares. Of all the outcome measures examined, GAS was the most responsive to change (SRM 0.89 to −0.53). Of the GIS domains, the gout concern overall domain had the best sensitivity to change (SRM 1.06–0.01). Conclusion GAS is sensitive to change, has predictive validity and correlates with relevant domains of GIS such as gout concern overall. Additional independent validation of GAS is required before it can be adopted in clinical practice.