Secondary use of patient data within decentralized studies using the example of rare diseases in Germany: A data scientist's exploration of process and lessons learned.

Objective: Unlocking the potential of routine medical data for clinical research requires the analysis of data from multiple healthcare institutions. However, according to German data protection regulations, data can often not leave the individual institutions and decentralized approaches are needed. Decentralized studies face challenges regarding coordination, technical infrastructure, interoperability and regulatory compliance.

[CF Lung Disease - a German S3 Guideline: Pseudomonas aeruginosa].

Cystic Fibrosis (CF) is the most common autosomal recessive genetic multisystemic disease. In Germany, it affects at least 8000 people. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel.

Effect of a 1-year physical activity intervention on quality of life, fatigue, and distress in adult childhood cancer survivors-A randomized controlled trial (SURfit).

Introduction: Childhood cancer survivors (CCS) are at risk of experiencing lower quality-of-life, fatigue, and depression. Few randomized controlled trials have studied the effect of physical activity (PA) on these in adult long-term CCS. This study investigated the effect of a 1-year individualized PA intervention on health-related quality-of-life (HRQOL), fatigue, and distress symptoms in adult CCS.

Effect of the addition of a mental health specialist for evaluation of undiagnosed patients in centres for rare diseases (ZSE-DUO): a prospective, controlled trial with a two-phase cohort design.

Background: People with complex symptomatology but unclear diagnosis presenting to a centre for rare diseases (CRD) may present with mental (co-)morbidity. We hypothesised that combining an expert in somatic medicine with a mental health specialist working in tandem will improve the diagnostic outcome.

Methods: Patients aged 12 years and older who presented to one of the 11 participating German CRDs with an unknown diagnosis were recruited into this prospective cohort trial with a two-phase cohort design.

Effect of a 1-year physical activity intervention on cardiovascular health in long-term childhood cancer survivors-a randomised controlled trial (SURfit).

Background: This randomised controlled trial (RCT) assessed the effect of a 1-year, partially supervised, physical activity (PA) intervention on a cardiovascular disease (CVD) risk score in adult survivors of childhood cancer.

Methods: We included childhood cancer survivors ≥16 y at enrolment, <16 y at diagnosis and ≥5 y in remission. The intervention group was asked to perform an additional ≥2.

Guidance and standard operating procedures for functional exercise testing in cystic fibrosis.

Regular exercise testing is recommended for all people with cystic fibrosis (PwCF). A range of validated tests, which integrate both strength and aerobic function, are available and increasingly being used. Together, these tests offer the ability for comprehensive exercise evaluation.

Lung Function in Patients with Cystic Fibrosis before and during -Modulator Therapy Using 3D Ultrashort Echo Time MRI.

Background The triple combination of the cystic fibrosis transmembrane regulator (CFTR) modulators elexacaftor, tezacaftor, and ivacaftor (hereafter, elexacaftor/tezacaftor/ivacaftor) has a positive effect on lung function in patients with cystic fibrosis (CF). Purpose To compare three-dimensional (3D) ultrashort echo time (UTE) MRI functional lung data to common functional lung parameters in assessing lung function in patients with CF undergoing elexacaftor/tezacaftor/ivacaftor therapy. Materials and Methods In this prospective feasibility study, 16 participants with CF consented to undergo pulmonary MRI with a breath-hold 3D UTE sequence at baseline (April 2018-June 2019) and follow-up (April-July 2021).

[Uncovering rare diseases in medical data-coding].

The ICD-10-GM coding system used in the German healthcare system only captures a minority of rare disease diagnoses. Therefore, information on the incidence and prevalence of rare diseases as well as necessary (financial) resources for the expert care required for evidence-based decisions by health insurers, care providers, and politicians are lacking. Furthermore, the missing information complicates and sometimes even precludes the generation of scientific knowledge on rare diseases.

Physical activity and exercise training in cystic fibrosis.

Background: Physical activity (including exercise) may form an important part of regular care for people with cystic fibrosis (CF). This is an update of a previously published review.

Objectives: To assess the effects of physical activity interventions on exercise capacity by peak oxygen uptake, lung function by forced expiratory volume in one second (FEV), health-related quality of life (HRQoL) and further important patient-relevant outcomes in people with cystic fibrosis (CF).

Effect of a physical activity intervention on lower body bone health in childhood cancer survivors: A randomized controlled trial (SURfit).

It remains controversial whether physical activity promotes bone health in childhood cancer survivors (CCS). We aimed to assess the effect of a one-year general exercise intervention on lower body bone parameters of CCS. CCS ≥16 years at enrollment, <16 years at diagnosis and ≥5 years in remission were identified from the national Childhood Cancer Registry.

Cystic fibrosis related diabetes is not associated with maximal aerobic exercise capacity in cystic fibrosis: a cross-sectional analysis of an international multicenter trial.

Background: Previous studies have reported differences in aerobic exercise capacity, expressed as peak oxygen uptake (VO), between people with and without cystic fibrosis (CF) related diabetes (CFRD). However, none of the studies controlled for the potential influence of physical activity on VO. We investigated associations between CFRD and VO following rigorous control for confounders including objectively measured physical activity.

[Quality of Life and Experienced Distress of Patients Suspected of having a Rare (Chronic) Health Condition - Initial Findings from the ZSE-DUO Study].

Objective: Patients suspected of having a rare (chronic) health condition have often gone a long way within the healthcare system. To date, little is known about the health-related quality of life of this group of patients. The study aims to describe the health-related quality of life and the perceived distress of patients suspected of having a rare (chronic) health condition and compare the results with standard values of the German population.

A case report of Sanfilippo syndrome - the long way to diagnosis.

Background: Mucopolysaccharidosis type III (Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in the heparan-N-sulfatase enzyme involved in the catabolism of the glycosaminoglycan heparan sulfate. It is characterized by early nonspecific neuropsychiatric symptoms, followed by progressive neurocognitive impairment in combination with only mild somatic features. In this patient group with a broad clinical spectrum a significant genotype-phenotype correlation with some mutations leading to a slower progressive, attenuated course has been demonstrated.

Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study.

Background: In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process.

Does allogeneic stem cell transplantation in survivors of pediatric leukemia impact regular physical activity, pulmonary function, and exercise capacity?

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved survival in high-risk childhood leukemia but is associated with long-term sequelae such as impaired pulmonary function and reduced exercise capacity impacting quality of life.

Methods: A convenience sample of 17 patients after allo-HSCT (HSCT-12 male, age 15.7±6.

Effects of a Partially Supervised Conditioning Program in Cystic Fibrosis: An International Multicenter, Randomized Controlled Trial (ACTIVATE-CF).

The long-term effects of vigorous physical activity (PA) on lung function in cystic fibrosis are unclear. To evaluate effects of a 12-month partially supervised PA intervention using motivational feedback. In a parallel-arm multicenter randomized controlled trial (ACTIVATE-CF), relatively inactive patients aged at least 12 years were randomly assigned (1:1 ratio) to an intervention group or control group.

[Centers for rare diseases-Structures, tasks and networks].

People suffering from rare diseases are optimally treated in specialized centers with an interdisciplinary and multiprofessional team. These centers are also actively involved in research and provide all levels of teaching and education with respect to a single disease or a group of diseases. In Germany, there are now more than 30 reference or so-called type A centers for rare diseases located at university hospitals, which undertake these tasks with their associated disease (group)-specific type B or specialist centers.

Report of two siblings with spondylodysplastic Ehlers-Danlos syndrome and B4GALT7 deficiency.

Background: The spondylodysplastic Ehlers-Danlos subtype (OMIM #130070) is a rare connective tissue disorder characterized by a combination of connective tissue symptoms, skeletal features and short stature. It is caused by variants in genes encoding for enzymes involved in the proteoglycan biosynthesis or for a zinc transporter.

Presentation Of Cases: We report two brothers with a similar phenotype of short stature, joint hypermobility, distinct craniofacial features, developmental delay and severe hypermetropia indicative for a spondylodysplastic Ehlers-Danlos subtype.

Persistent tachypnea of infancy: Follow up at school age.

Background: Persistent tachypnea of infancy (PTI) is a rare pediatric lung disease of unknown origin. The diagnosis can be made by clinical presentation and chest high resolution computed tomography after exclusion of other causes. Clinical courses beyond infancy have rarely been assessed.

Three-dimensional Ultrashort Echotime Magnetic Resonance Imaging for Combined Morphologic and Ventilation Imaging in Pediatric Patients With Pulmonary Disease.

Purpose: Ultrashort echotime (UTE) sequences aim to improve the signal yield in pulmonary magnetic resonance imaging (MRI). We demonstrate the initial results of spiral 3-dimensional (3D) UTE-MRI for combined morphologic and functional imaging in pediatric patients.

Methods: Seven pediatric patients with pulmonary abnormalities were included in this observational, prospective, single-center study, with the patients having the following conditions: cystic fibrosis (CF) with middle lobe atelectasis, CF with allergic bronchopulmonary aspergillosis, primary ciliary dyskinesia, air trapping, congenital lobar overinflation, congenital pulmonary airway malformation, and pulmonary hamartoma.