The UK myotonic dystrophy patient registry: facilitating and accelerating clinical research

Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy worldwide with complex, multi-systemic, and progressively worsening symptoms. There is currently no treatment for this inherited disorder and research can be challenging due to the rarity and variability of the disease. The UK Myotonic Dystrophy Patient Registry is a patient self-enrolling online database collecting clinical and genetic information. For this cross-sectional “snapshot” analysis, 556 patients with a confirmed diagnosis of DM1 registered between May 2012 and July 2016 were included. An almost even distribution was seen between genders and a broad range of ages was present from 8 months to 78 years, with the largest proportion between 30 and 59 years. The two most frequent symptoms were fatigue and myotonia, reported by 79 and 78% of patients, respectively. The severity of myotonia correlated with the severity of fatigue as well as mobility impairment, and dysphagia occurred mostly in patients also reporting myotonia. Men reported significantly more frequent severe myotonia, whereas severe fatigue was more frequently reported by women. Cardiac abnormalities were diagnosed in 48% of patients and more than one-third of them needed a cardiac implant. Fifteen percent of patients used a non-invasive ventilation and cataracts were removed in 26% of patients, 65% of which before the age of 50 years. The registry’s primary aim was to facilitate and accelerate clinical research. However, these data also allow us to formulate questions for hypothesis-driven research that may lead to improvements in care and treatment

A guide to interpreting estimated median age of survival in cystic fibrosis patient registry reports.

Survival statistics, estimated using data collected by national cystic fibrosis (CF) patient registries, are used to inform the CF community and monitor survival of CF populations. Annual registry reports typically give the median age of survival, though different registries use different estimation approaches and terminology, which has created confusion for the community. In this article we explain how median age of survival is estimated, what its interpretation is, and what assumptions and limitations are involved. Information on survival from birth is less useful for individuals who have already reached a certain age and we propose use of conditional survivor curves to address this. We provide recommendations for CF registries with the aim of facilitating clear and consistent reporting of survival statistics. Our recommendations are illustrated using data from the UK Cystic Fibrosis Registry

Volumetric laser endomicroscopy and its application to Barrett's esophagus: results from a 1,000 patient registry.

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291

A register-based study:cough - a frequent phenomenon in the adult population

BACKGROUND: Chronic cough, more than 8 weeks, can either be without co-morbidity called unexplained chronic cough (UCC) or with co-morbidity called refractory chronic cough (RCC). Using datasets from the Danish National Prescription Registry (Prescription Registry) and Danish National Patient Registry (Patient Registry) we wanted to investigate the prevalence and factors of importance of cough in a Nationwide registry. MATERIAL AND METHODS: Inclusion criteria were patients 18–90 years with at least one final cough diagnosis (ICD-10 DR05/DR059) in Patient registry or patients who have redeemed ≥2 prescriptions for relevant cough-medication within a 90-day harvest in the Prescription registry from 2008 to 2017. To validate this study’s chosen proxy on chronic cough an analysis of the Patient registry sub-population with a contact of ≥8 weeks and then final diagnosis code DR05/DR059 was also performed. The population was divided into UCC and RCC. RESULTS: Of the 104,216 patients from the Prescription registry, 52,727 were classified as having UCC and 51,489 were classified with RCC. From the Patient registry 34,260 were included, of whom 12,278 had UCC and 21,982 had RCC. Cough were frequently found among females (p < 0.0001). Both genders were around 2 years older in RCC than UCC (p < 0.0001) Spirometry was performed in 69 and 57%, X-ray in 73 and 58% and asthma challenge test performed in 13 and 5% (UCC and RCC, respectively, p < 0.0001). The frequency of co-morbidities such as heart failure, rheumatologic disease, pulmonary embolism, and diabetes was < 10%. CONCLUSION: Many patients suffer from chronic cough or cough requiring medications, with or without co-morbidity; frequently found among menopausal women. Most patients had a substantial work-up performed. The high frequency and the resources consuming work-up program call for systematic coding of disease, systematic patient evaluation and more specific treatment options. The study was approved (ID: no. P-2019-191)

The International Working Group on Neurotransmitter related Disorders (iNTD): A worldwide research project focused on primary and secondary neurotransmitter disorders

INTRODUCTION: Neurotransmitters are chemical messengers that enable communication between the neurons in the synaptic cleft. Inborn errors of neurotransmitter biosynthesis, breakdown and transport are a group of very rare neurometabolic diseases resulting in neurological impairment at any age from newborn to adulthood. METHODS AND RESULTS: The International Working Group on Neurotransmitter related Disorders (iNTD) is the first international network focusing on the study of primary and secondary neurotransmitter disorders. It was founded with the aim to foster exchange and improve knowledge in the field of these rare diseases. The newly established iNTD patient registry for neurotransmitter related diseases collects longitudinal data on the natural disease course, approach to diagnosis, therapeutic strategies, and quality of life of affected patients. The registry forms the evidence base for the development of consensus guidelines for patients with neurotransmitter related disorders. CONCLUSION: The iNTD network and registry will improve knowledge and strengthen research capacities in the field of inborn neurotransmitter disorders. The evidence-based guidelines will facilitate standardized diagnostic procedures and treatment approaches

Nationwide patient registry for GNE myopathy in Japan

BACKGROUND: GNE myopathy is a slowly progressive autosomal recessive myopathy caused by mutations in the GNE (glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase) gene. This study aimed to (1) develop a nationwide patient registry for GNE myopathy in order to facilitate the planning of clinical trials and recruitment of candidates, and (2) gain further insight into the disease for the purpose of improving therapy and care. METHODS: Medical records of genetically-confirmed patients with GNE myopathy at the National Center Hospital of the National Center of Neurology and Psychiatry (NCNP) were retrospectively reviewed in order to obtain data reflecting the severity and progression of the disease. We also referred to items in the datasheet of the nationwide registry of dystrophinopathy patients in the Registry of Muscular Dystrophies (Remudy). Items selected for the registration sheet included age, sex, age at onset, past history and complications, family history, body weight and height, pathological findings of muscle biopsy, grip power, walking ability, respiratory function, cardiac function, willingness to join upcoming clinical trials, and participation in patient associations. A copy of the original genetic analysis report was required of each patient. RESULTS: We successfully established the Remudy-GNE myopathy. Currently, 121 patients are registered nationwide, and 93 physicians from 73 hospitals collaborated to establish the registry. The mean age at onset was 27.7 ± 9.6 years, and 19.8% (24/121) of patients could walk without assistance. Mean presumed durations from onset to use of assistive devices (cane and/or braces) and a wheelchair, and loss of ambulation were 12.4, 15.2, and 21.1 years, respectively. Three patients had a past history and/or complication of idiopathic thrombocytopenia. To share the progress of this study with the community, newsletters were published on a regular basis, and included information regarding new phase I clinical trials for GNE myopathy. The newsletters also served as a medium to bring attention to the importance of respiratory evaluation and care for respiratory insufficiency. CONCLUSION: The Japanese Remudy-GNE myopathy is useful for clarifying the natural history of the disease and recruiting patients with genetically-confirmed GNE myopathy for clinical trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13023-014-0150-4) contains supplementary material, which is available to authorized users

Southern Alberta Vasculitis Patient Registry: Creation and Utility

INTRODUCTION Vasculitides encompass a group of rare diseases where inflammation of vessels causes multisystem organ damage. Incidence, currently estimated to be 10-20/million/year, shows an increasing trend in both children and adults [1]. Due to the nature of the disease, patients need ongoing follow-up to prevent relapse, avert organ damage, and control factors associated with increased mortality. However, vasculitides can be difficult to diagnose due to the diversity of presentation and lack of disease-specific diagnostic tools. As with other rare diseases, the limited number of patients impairs recruitment into clinical trials, impedes research, and hinders the generation of evidence-based treatment recommendations and protocols [2]. Moreover, the low patient numbers provide a barrier to obtaining reliable rare disease prevalence statistics and to gaining a clear understanding of the natural history of specific vasculitides. To address some of these limitations, we propose to generate a prospective vasculitis registry for patients in Southern Alberta. This initial registry will serve as a foundation for collaboration with other centres at the provincial, national, and international levels (Figure 1). The establishment of such a registry will create a framework for knowledge translation, discovery, and best practice management. METHODS Recruitment will initially be limited to patients with vasculitis residing in Southern Alberta referred to the Rheumatology division in Calgary through the central triage system. Ethics approval was obtained in May 2012. Patients complete written informed consent at their baseline visit. Upon consenting, the patients are examined yearly by Dr. Aurore Fifi-Mah, a Rheumatologist at the South Health Campus in Calgary, Alberta. Patients also complete yearly clinical case report forms and a Patient Quality of Life form (SF-36). Patient consent also extends to the collection of de-identified sera for storage in the Mitogen Advanced Diagnostics Laboratory in Calgary, Alberta, under the direction of Dr. Fritzler. These sera will be analyzed for the presence of new target antibodies and proteins to enhance understanding of the pathogenesis and prognosis of vasculitis. As this is an observational study, no power calculation is involved. Descriptive analysis will be used to summarize participant characteristics and comorbid conditions. RESULTS The initial project infrastructure has been successfully established. To date, 107 patients have been recruited with the following diagnosis (patient numbers are in brackets): ANCA-associated Vasculitis (12), Behcet’s Disease (7), Connective Tissue Disease (6), CNS Vasculitis (4), Cryoglobulinemia (1), Giant Cell Arteritis (9), IgA Vasculitis (5), Leukoclastic Angiitis (11), Neurosarcoidosis (1), NMDA Receptor Encephalitis (1), Polyarteritis Nodosa (11), Polymyalgia Rheumatica (13), Takayasu’s Arteritis (6), and Vasculitis Associated with Other Disease (20).DISCUSSION AND CONCLUSIONS The establishment of a Southern Alberta Vasculitis Patient Registry addresses the pervasive issues of inaccurate rare disease statistics, inadequate understanding of disease natural history, and limited diagnostic and treatment regimes. Through systematic collection and analysis of data, the registry will create a foundation of knowledge on which to build informed, standardized models of care. Moreover, the additional benefit of serum analysis may permit the discovery of specific biomarkers and prognostic factors to classify and predict the future course of different vasculitis subtypes. This will permit individualized, patient-centred treatment. The extension of this project to include centres provincially, nationally, and internationally would magnify the utility of the initial project. The previous establishment of provincially-based vasculitis research centres through CanVasc expedites project expansion