MoRe – Mobile Research: App-basierte Studien nach dem Baukastenprinzip

Die Erfassung der Effektivität von Behandlungsmethoden sowie von Therapieergebnissen steht in einer ergebnisorientierten medizinischen Versorgung immer mehr im Vordergrund klinischen und wissenschaftlichen Interesses. Daher erwarten Experten von mobilen Gesundheitslösungen (mHealth) unter anderem Verbesserungen in der Gesundheitsvorsorge und Krankheitsfrüherkennung, Kosteneinsparungen und/oder Qualitätsverbesserungen in der Leistungserbringung. Ziel des Projektes ist die Etablierung einer universellen Applikation, die es dem Anwender ermöglicht - entsprechend aktueller Standards in Bezug auf Patientensicherheit und Datenschutz und guter klinischer Praxis - ohne individuelle Programmierkenntnisse ein eigenes Forschungsprojekt zur systematischen und hochwertigen Datenerfassung von Patienten mit unterschiedlichsten Pathologien zusammenzustellen. Dabei werden, gemäß der immer wichtiger werdenden Versorgungsforschung, Patient-reported Outcome Parameter als wertvolles und zunehmend etabliertes Instrument zur Untersuchung von Therapieergebnissen eingesetzt. Lebensqualität als wichtiger messbarer Parameter bei nicht-vitalen Indikationen sei hier nur als Beispiel genannt. Zusammengestellte Studien werden über eine Smartphone-App für den Patienten zugänglich. Die hierdurch erfassten Daten kann der Wissenschaftler über eine webbasierte Oberfläche analysieren und zur weiteren Auswertung herunterladen. Öffentliche Studien können weltweit innerhalb der App gesucht werden. Geschlossene Studien sind privat

Treatment With Erythropoietin for Patients With Optic Neuritis: Long-term Follow-up.

BACKGROUND AND OBJECTIVE Erythropoietin (EPO) is a candidate neuroprotective drug. We assessed its long-term safety and efficacy as an adjunct to methylprednisolone in patients with optic neuritis and focused on conversions to multiple sclerosis (MS). METHODS The TONE trial randomized 108 patients with acute optic neuritis but without previously known MS to either 33,000 IU EPO or placebo in conjunction with 1,000 mg methylprednisolone daily for 3 days. After reaching the primary end point at 6 months, we conducted an open-label follow-up 2 years after randomization. RESULTS The follow-up was attended by 83 of 103 initially analyzed patients (81%). There were no previously unreported adverse events. The adjusted treatment difference of peripapillary retinal nerve fiber layer atrophy in relation to the fellow eye at baseline was 1.27 µm (95% CI -6.45 to 8.98, p = 0.74). The adjusted treatment difference in low-contrast letter acuity was 2.87 on the 2.5% Sloan chart score (95% CI -7.92 to 13.65). Vision-related quality of life was similar in both treatment arms (National Eye Institute Visual Functioning Questionnaire median score [IQR]: 94.0 [88.0 to 96.9] in the EPO and 93.4 [89.5 to 97.4] in the placebo group). The rate of multiple sclerosis-free survival was 38% in the placebo and 53% in the EPO group (hazard ratio: 1.67, 95% CI 0.96 to 2.88, p = 0.068). DISCUSSION In line with the results at 6 months, we found neither structural nor functional benefits in the visual system of patients with optic neuritis as a clinically isolated syndrome, 2 years after EPO administration. Although there were fewer early conversions to MS in the EPO group, the difference across the 2-year window was not statistically significant. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that for patients with acute optic neuritis, EPO as an adjunct to methylprednisolone is well tolerated and does not improve long-term visual outcomes. TRIAL REGISTRATION INFORMATION The trial was preregistered before commencement at clinicaltrials.gov (NCT01962571)

Subjektorientierung in der Medizin

Subjektorientierung in der Medizin – Anspruch oder Wirklichkeit Hintergrund: Abläufe innerhalb der Medizin sind geprägt durch administrative Anforderungen, ein persönlicher Freiraum für Ärztinnen und Ärzte scheint im klinischen Alltag klein. Beratung zu klinischen Studien ist eine besondere Form der Kommunikation zwischen ärztlichem Personal und seinen Patientinnen und Patienten. Um dem Anspruch aus Normen, Gesprächsmodellen und anderen Herausforderungen gerecht zu werden, ist Grundvoraussetzung, dass ärztliches Personal seine Patientinnen und Patienten kennt. Hierfür konnte bislang keine Publikation gefunden werden. Methoden: Die Themen Information, Aufklärung und Beratung im Gesundheitswesen wurden von verschiedenen Blickwinkeln aus beleuchtet. Dabei wurde eine besondere Gesprächssituation – ein normierter Kommunikationsprozess im Rahmen klinischer Studien – näher untersucht. Anhand eines Fragebogens wurde die Übereinstimmung von einerseits den Angaben der Patientinnen und Patienten zu Gründen für oder gegen die Teilnahme an einer klinischen Studie und andererseits den entsprechenden Aussagen der beratenden Ärztinnen und Ärzte diesbezüglich ermittelt. Ergebnisse: Bei 36 Studienteilnehmenden, 18 Gesprächspaaren, ergab die Auswertung, dass ärztliches Personal seine Patientinnen und Patienten durchschnittlich gut kannte. Je besser Ärztinnen und Ärzte angaben, die jeweiligen Patientinnen und Patienten zu kennen, desto besser waren die Ergebnisse. Sowohl die Teilnahme an Kommunikationsfortbildungen, vor allem aber die zunehmende Anzahl an Berufsjahren zeigte eine positive Tendenz. Ärztinnen zeigten bessere Ergebnisse als Ärzte. Schlussfolgerungen: Die Ergebnisse bestätigen die Notwendigkeit weiterer Untersuchungen.Orientation to Subjects in Medicine – Reality or Wishful Thinking? Background: Processes within medicine are characterized by administrative requirements. A personal approach for doctors seems limited in clinical practice. Informed consent is a special form of communication between physicians and their patients. Medical personnel have to conform to standards, models and face challenges. In this context the basic requirement for physicians is to know the patient. Until now, no publication on this subject has been available. Methods: The topics information, education and counselling in healthcare has been reflected on from different perspectives. A special communication situation was further investigated: an informed consent situation in the context of clinical trials. Using a questionnaire, the empirical part evaluates the concordance between the reasons that patients have for or against participating in a clinical trial and the reasons clinicians assume they have. Results: The evaluation of 36 study participants, 18 physician-patient pairs, showed that medical staff knew their patients well on average. The better doctors claimed to know the respective patient, the better the results. Doctors who participated in vocational training showed a tendency to better results. Especially the number of years of employment also positively affected the results in this study. Female doctors showed better results than male doctors. Conclusions: The results confirm the need for further investigation

Abstoßungsprophylaxe bei Hornhautübertragung : Eine randomisierte Studie zum HLA-Abgleich (FANCY-Studie)

BACKGROUND: Graft rejection. Twenty to thirty percent of patients with corneal transplants experience at least one rejection episode in the first 5 years after transplantation. Prophylaxis through matching for human leukocyte antigens (HLA) is controversial. We herein report the results of the Functional ANtigen matChing in keratoplastY (FANCY) trial. METHODS: FANCY was a randomized, double-blind, multicenter clinical trial. The primary objective was to evaluate superiority of HLA matching versus random graft assignment. The primary endpoint was rejection-free graft survival. We included both normal-risk and high-risk indications. The study is registered with ClinicalTrials. gov (NCT00810472). RESULTS: 721 patients were included, 639 patients were randomized. 474 patients underwent keratoplasty within the study; 165 patients received grafts outside the trial. One patient died and one patient was lost to follow up. We observed 33 graft rejections in the HLA matching arm (n = 224). The corresponding estimated cumulative incidence rate of immune reactions after two years was 15.7%. We observed 40 rejections in the control arm (n = 249). After two years this yields an estimated cumulative incidence rate of 17%. CONCLUSION: In our heterogenous study group, HLA matching did not show a significant advantage compared to random graft assignment. The rejection rate in our sample was lower than expected. Therefore no definite conclusions can be drawn as to whether HLA matching is beneficial in corneal transplantation

Safety and efficacy of erythropoietin for the treatment of patients with optic neuritis (TONE): a randomised, double-blind, multicentre, placebo-controlled study.

BACKGROUND The human cytokine erythropoietin conveys neuroprotection in animal models but has shown ambiguous results in phase 2 clinical trials in patients with optic neuritis. We assessed the safety and efficacy of erythropoietin in patients with optic neuritis as a clinically isolated syndrome in a multicentre, prospective, randomised clinical trial. METHODS This randomised, placebo-controlled, double-blind phase 3 trial, conducted at 12 tertiary referral centres in Germany, included participants aged 18-50 years, within 10 days of onset of unilateral optic neuritis, with visual acuity of 0·5 or less, and without a previous diagnosis of multiple sclerosis. Participants were randomly assigned (1:1) to receive either 33 000 IU erythropoietin or placebo intravenously for 3 days as an adjunct to high-dose intravenous methylprednisolone (1000 mg per day). Block randomisation was performed by the trial statistician using an SAS code that generated randomly varying block sizes, stratified by study site and distributed using sealed envelopes. All trial participants and all study staff were masked to treatment assignment, except the trial pharmacist. The first primary outcome was atrophy of the peripapillary retinal nerve fibre layer (pRNFL), measured by optic coherence tomography (OCT) as the difference in pRNFL thickness between the affected eye at week 26 and the unaffected eye at baseline. The second primary outcome was low contrast letter acuity at week 26, measured as the 2·5% Sloan chart score of the affected eye. Analysis was performed in the full analysis set of all randomised participants for whom treatment was started and at least one follow-up OCT measurement was available. Safety was analysed in all patients who received at least one dose of the trial medication. This trial is registered at ClinicalTrials.gov, NCT01962571. FINDINGS 108 participants were enrolled between Nov 25, 2014, and Oct 9, 2017, of whom 55 were assigned to erythropoietin and 53 to placebo. Five patients were excluded from the primary analysis due to not receiving the allocated medication, withdrawn consent, revised diagnosis, or loss to follow-up, yielding a full analysis set of 52 patients in the erythropoietin group and 51 in the placebo group. Mean pRNFL atrophy was 15·93 μm (SD 14·91) in the erythropoietin group and 14·65 μm (15·60) in the placebo group (adjusted mean treatment difference 1·02 μm; 95% CI -5·51 to 7·55; p=0·76). Mean low contrast letter acuity scores were 49·60 (21·31) in the erythropoietin group and 49·06 (21·93) in the placebo group (adjusted mean treatment difference -4·03; -13·06 to 5·01). Adverse events occurred in 43 (81%) participants in the erythropoietin group and in 42 (81%) in the placebo group. The most common adverse event was headache, occuring in 15 (28%) patients in the erythropoietin group and 13 (25%) patients in the placebo group. Serious adverse events occurred in eight (15%) participants in the erythropoietin and in four (8%) in the placebo group. One patient (2%) in the erythropoietin group developed a venous sinus thrombosis, which was treated with anticoagulants and resolved without sequelae. INTERPRETATION Erythropoietin as an adjunct to corticosteroids conveyed neither functional nor structural neuroprotection in the visual pathways after optic neuritis. Future research could focus on modified erythropoietin administration, assess its efficacy independent of corticosteroids, and investigate whether it affects the conversion of optic neuritis to multiple sclerosis. FUNDING German Federal Ministry of Education and Research (BMBF)

Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol.

INTRODUCTION Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function. METHODS AND ANALYSIS Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to ≤0.5 (decimal system) and an onset of symptoms within 10 days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33 000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30 months. ETHICS AND DISSEMINATION TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki, local laws and ICH-GCP. TRIAL REGISTRATION NUMBER NCT01962571