Unveiling the untreated: development of a database algorithm to identify potential Fabry disease patients in Germany.

Background: Fabry disease (FD), an X-linked lysosomal storage disorder, is caused by mutations in the gene encoding α-galactosidase A, resulting in lysosomal accumulation of globotriaosylceramide and other glycosphingolipids. Early detection of FD is challenging, accounting for delayed diagnosis and treatment initiation. This study aimed to develop an algorithm using a logistic regression model to facilitate early identification of patients based on ICD-10-GM coding using a German Sickness Fund Database.

Effect of avalglucosidase alfa on disease-specific and general patient-reported outcomes in treatment-naïve adults with late-onset Pompe disease compared with alglucosidase alfa: Meaningful change analyses from the Phase 3 COMET trial.

Background: The Phase 3 COMET trial (NCT02782741) comparing avalglucosidase alfa and alglucosidase alfa included health-related quality of life (HRQoL) assessments in treatment-naïve patients with late-onset Pompe disease (LOPD). Here, we further characterize results from disease-specific and general patient-reported outcome (PRO) measures.

Methods: Adults who participated in the COMET trial receiving avalglucosidase alfa or alglucosidase alfa (both 20 mg/kg biweekly) during the 49-week double-blind treatment period were included in the analysis.

Measurement Properties of 2 Novel PROs, the Pompe Disease Symptom Scale and Pompe Disease Impact Scale, in the COMET Study.

Background And Objectives: The Pompe Disease Symptom Scale (PDSS) and Impact Scale (PDIS) were created to measure the severity of symptoms and functional limitations experienced by patients with late-onset Pompe disease (LOPD). The objectives of this analysis were to establish a scoring algorithm and to examine the reliability, validity, and responsiveness of the measures using data from the COMET clinical trial.

Methods: The COMET trial was a randomized, double-blind study comparing the efficacy and safety of avalglucosidase alfa and alglucosidase alfa in patients with LOPD aged 16-78 years at baseline.

Development of the Cold Agglutinin Disease Symptoms and Impact Questionnaire (CAD-SIQ).

Objectives: Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia. This study aimed to identify disease-related symptoms and impacts important to patients with CAD, and to develop a novel CAD-specific patient-reported outcome measure.

Methods: Adults with CAD were randomly selected from a United States patient panel to participate in concept elicitation (CE) interviews to identify important symptoms and impacts or cognitive debriefing (CD) interviews to assess the comprehension and relevance of the draft item set.

Venglustat, an orally administered glucosylceramide synthase inhibitor: Assessment over 3 years in adult males with classic Fabry disease in an open-label phase 2 study and its extension study.

Venglustat inhibits the enzymatic conversion of ceramide to glucosylceramide, reducing available substrate for the synthesis of more complex glycosphingolipids. It offers a potential new approach to the treatment of patients with Fabry disease (α-Gal A deficiency), in whom progressive accumulation of such glycosphingolipids, including globotriaosylceramide (GL-3), in the lysosomes of a wide range of cell types often leads to vital organ complications in adulthood. An international, open-label, single-arm, Phase 2a uncontrolled 26-week clinical study (NCT02228460) and a 130-week extension study (NCT02489344) were conducted to assess the safety, pharmacodynamics, pharmacokinetics, and exploratory efficacy of 15 mg once daily oral venglustat in treatment-naïve adult male patients with classic Fabry disease.

Clinical relevance of globotriaosylceramide accumulation in Fabry disease and the effect of agalsidase beta in affected tissues.

Fabry disease (FD) is a rare lysosomal storage disorder, characterized by a reduction in α-galactosidase A enzyme activity and the progressive accumulation of globotriaosylceramide (GL3) and its metabolites in the cells of various organs. Agalsidase beta, an enzyme replacement therapy (ERT), is approved for use in patients with FD in Europe, Canada, Australia, South America, and Asia, and is the only ERT approved for use in the United States. In this review, we discuss the clinical relevance of GL3 accumulation, the effect of agalsidase beta on GL3 in target tissues, and the association between treatment-related tissue GL3 clearance and long-term structure, function, or clinical outcomes.

Health-related quality of life, direct medical and societal costs among children with moderate or severe haemophilia in Europe: multivariable models of the CHESS-PAEDs study.

Background: Haemophilia bears substantial humanistic and economic burden on children and their caregivers. Characterising the differential impact of severe versus moderate paediatric haemophilia is important for clinical and health policy decisions. We analysed health-related quality of life (HRQoL), annual direct medical (excluding factor treatment costs), non-medical and societal costs among children and adolescents with moderate and severe haemophilia A or B without inhibitors from the European CHESS-PAEDs study.

Differential humanistic and economic burden of mild, moderate and severe haemophilia in european adults: a regression analysis of the CHESS II study.

Background: The lifelong nature of haemophilia makes patient-centred and societal assessments of its impact important to clinical and policy decisions. Quantifying the humanistic and economic burden by severity is key to assessing the impact on healthcare systems. We analysed the annual direct medical (excluding factor replacement therapy costs) and non-medical costs as well as societal costs and health-related quality of life (HRQoL) of mild, moderate and severe disease among adults with haemophilia A or B without inhibitors in Europe.

Fabry Disease Patient-Reported Outcome (FD-PRO) demonstrates robust measurement properties for assessing symptom severity in Fabry disease.

Background: Fabry disease (FD) is a rare, genetic disease, that if untreated, progresses to irreversible and life-threatening renal, cardiac, and cerebrovascular events. FD symptoms impact daily functioning and quality of life, but no disease-specific measure of these symptoms has been psychometrically tested.

Methods: The Fabry Disease Patient-Reported Outcome (FD-PRO) consists of 19 items that measure neuropathic symptoms (pain, tingling, numbness and burning in upper/lower extremities), headache, abdominal pain, heat intolerance, swelling, tinnitus, fatigue, hearing/vision impairment, hypohidrosis (diminished sweating) and difficulty engaging in regular physical activities in the past 24 h.

Cost-Effectiveness Analysis of rFVIIIFc Versus Contemporary rFVIII Treatments for Patients with Severe Hemophilia A Without Inhibitors in the United States.

Background: A range of treatments for patients with severe hemophilia A (HA) have been developed over the last decade, allowing for reduced frequency of administration and improved outcomes (joint health and breakthrough bleeding rates). While clinically effective, the cost effectiveness of these treatments has not been established.

Objective: This study presents a cost-effectiveness analysis of contemporary rFVIII treatments for severe HA patients without inhibitors.

Development of the Fabry Disease Patient-Reported Outcome (FD-PRO): a new instrument to measure the symptoms and impacts of Fabry Disease.

Background: The systematic collection of disease-specific symptoms and impacts on the lives of patients with Fabry Disease (FD) can offer unique insights into the patient experience, yet no disease-specific tool to measure FD symptoms exists. This study describes the development of the Fabry Disease Patient-Reported Outcome (FD-PRO).

Methods: A targeted literature search, interviews with key opinion leaders (KOLs), and concept elicitation (CE) interviews with patients identified the most frequent signs and symptoms associated with FD and their impact on daily life.

Agalsidase beta treatment slows estimated glomerular filtration rate loss in classic Fabry disease patients: results from an individual patient data meta-analysis.

Background: Fabry disease is a rare, X-linked genetic disorder that, if untreated in patients with the Classic phenotype, often progresses to end-stage kidney disease. This meta-analysis determined the effect of agalsidase beta on loss of estimated glomerular filtration rate (eGFR) in the Classic phenotype using an expansive evidence base of individual patient-level data.

Methods: The evidence base included four Sanofi-Genzyme studies and six studies from a systematic literature review.

Limited Generalizability of a Retrospective Chart Review Comparing 3 Recombinant FVIII Products for Hemophilia A Prophylaxis.

No funding supported the writing of this letter. Preblick, Ali, and DasMahapatra are employees and shareholders of Sanofi Genzyme. Gray is a postdoctoral fellow at Sanofi Genzyme and Rutgers University.

Treatment Satisfaction and Burden of Illness in Patients with Newly Diagnosed Multiple Myeloma.

Objectives: This observational study identified attributes of patient-reported satisfaction with therapy for multiple myeloma (MM), described the treatment-related time burden and indirect costs, and investigated the effect of administration route (oral vs. injectable) on these outcomes among patients with newly diagnosed MM (NDMM) and among caregivers.

Methods: Patients residing in the USA with a self-reported diagnosis of NDMM were recruited from PatientsLikeMe, MyelomaCrowd, and Facebook (16 December 2016 and 6 July 2017) to complete an electronic survey including questions on treatment experience, economic burden, and standardized patient-reported outcome measures, including the Treatment Satisfaction Questionnaire for Medication with three domains (global satisfaction, effectiveness, and convenience) and the Work Productivity and Activity Impairment Questionnaire.

In search of a daily physical activity "sweet spot": Piloting a digital tracking intervention for people with multiple sclerosis.

Objective: This pilot study tested a course-based intervention to help people with multiple sclerosis (MS) match their daily activity to symptom severity ("sweet spot") using wearable activity trackers.

Methods: This two-phase study recruited online research network members reporting MS and who were utilizing Fitbit One™ activity trackers. In the first phase, participant interviews assessed demand based on physical activity and the use of behavior-change techniques.

Patient-Reported Factors in Treatment Satisfaction in Patients with Relapsed/Refractory Multiple Myeloma (RRMM).

Background: Therapy choices in relapsed/refractory multiple myeloma (RRMM) should consider patient satisfaction with treatment, because it is associated with adherence to therapy, health outcomes, and medical safety. The primary objective of this pilot cross-sectional observational study was to ascertain factors associated with patient-reported treatment satisfaction in RRMM.

Patients And Methods: Patients with a self-reported diagnosis of RRMM recruited from PatientsLikeMe, MyelomaCrowd, and Facebook were administered an electronic survey that included questions on demographics and clinical history, treatment experience, economic burden, and standardized patient-reported outcome measures, including the Treatment Satisfaction Questionnaire for Medication, Eastern Cooperative Oncology Group performance status (ECOG PS) measure, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem V2.

Mobility assessment using wearable technology in patients with late-onset Pompe disease.

Late-onset Pompe disease (LOPD) is a rare genetic disorder due to the absence or deficiency of acid alpha-glucosidase enzyme resulting in slowly progressing reduction of muscle strength, causing difficulties with mobility and respiration. Wearable technologies offer novel options to evaluate mobility in a real-world setting. LOPD patients self-reporting LOPD, ≥18 years, US residents, walking (with or without aid), and not on invasive ventilation were recruited for a 6- to 8-week wearable study via patient organizations.

Free-Living Physical Activity Monitoring in Adult US Patients with Multiple Sclerosis Using a Consumer Wearable Device.

Introduction: Wearable devices have been used to characterize physical activity in multiple sclerosis (MS). The objectives of this study were to advance the literature on the utility of free-living physical activity tracking from secondary analyses of a pilot study in MS patients.

Method: The original observational study was conducted in participants with MS at PatientsLikeMe (PatientsLikeMe (www.

Clinical trials from the patient perspective: survey in an online patient community.

Background: Developing new medicines relies on the successful conduct of clinical trials. As trial protocols become more arduous, it becomes harder to recruit and retain patient volunteers, although recent efforts such as OMERACT and I-SPY2 show that partnering with patients can be beneficial. We sought to describe drivers and barriers to trial participation, as well as condition-specific trial preferences.

Factors in Patient Empowerment: A Survey of an Online Patient Research Network.

Background: Providers and healthcare organizations have begun recognizing the importance of patient empowerment as a driver of patient-centered care. Unfortunately, most studies have investigated empowerment with single diseases. Identifying factors of empowerment across conditions and populations would enable a greater understanding of this construct.

Patient-centered activity monitoring in the self-management of chronic health conditions.

Background: As activity tracking devices become smaller, cheaper, and more consumer-accessible, they will be used more extensively across a wide variety of contexts. The expansion of activity tracking and personal data collection offers the potential for patient engagement in the management of chronic diseases. Consumer wearable devices for activity tracking have shown promise in post-surgery recovery in cardiac patients, pulmonary rehabilitation, and activity counseling in diabetic patients, among others.

A randomized controlled trial of an online self-management program for adults with arthritis pain.

The objective of this RCT was to assess the efficacy of an online pain self-management program with adults who had a self-reported doctor diagnosis of arthritis pain (N = 228). Participants were recruited via flyers and online postings then randomized to the experimental condition or the wait-list control condition. Individuals in the experimental condition reported significantly (1) increased arthritis self-efficacy and (2) reduced pain catastrophizing from baseline to follow up compared to those in the control condition.

Mediators and moderators of chronic pain outcomes in an online self-management program.

Objectives: Little is known about the moderators and mediators of change in online pain interventions based on cognitive-behavior therapy (CBT). We hypothesized that the effects of painACTION.com, an online pain self-management program, on pain-related outcomes would be mediated by changes in depression, anxiety, and stress, as well as the use of coping strategies.

Changes in prevalence of prescription opioid abuse after introduction of an abuse-deterrent opioid formulation.

Objective: The reformulation of oxycodone hydrochloride controlled-release (CR) tablets in August 2010 created a natural experiment at a national scale, providing an opportunity to evaluate patterns of abuse of prescription opioids and other drugs before and after introduction of this abuse-deterrent formulation (ADF).

Design: Observational, cross-sectional study

Setting: Sentinel sample of adults assessed for substance abuse treatment within the NAVIPPRO® surveillance system

Subjects: Two hundred thirty-two thousand and eight hundred seventy-four adults at 437 facilities during January 1, 2008 through December 31, 2011.

Methods: Time-series analysis using logistic regression to estimate quarterly prevalence of past 30-day abuse (adjusted for covariates and prescription volume) and changes in abuse pre-and post-ADF introduction.