Communication, Coordination, and Security for People with Multiple Sclerosis (COCOS-MS): a randomised phase II clinical trial protocol.

INTRODUCTION: Patients with multiple sclerosis (MS) have complex needs that range from organising one's everyday life to measures of disease-specific therapy monitoring to palliative care. Patients with MS are likely to depend on multiple healthcare providers and various authorities, which are often difficult to coordinate. Thus, they will probably benefit from comprehensive cross-sectoral coordination of services provided by care and case management (CCM). Though studies have shown that case management improves quality of life (QoL), functional status and reduces service use, such benefits have not yet been investigated in severely affected patients with MS. In this explorative phase ll clinical trial, we evaluated a CCM with long-term, cross-sectoral and outreaching services and, in addition, considered the unit of care (patients and caregivers). METHODS AND ANALYSIS: Eighty patients with MS and their caregivers will be randomly assigned to either the control (standard care) or the intervention group (standard care plus CCM (for 12 months)). Regular data assessments will be done at baseline and then at 3-month intervals. As primary outcome, we will evaluate patients' QoL. Secondary outcomes are patients' treatment-related risk perception, palliative care needs, anxiety/depression, use of healthcare services, caregivers' burden and QoL, meeting patients' and caregivers' needs, and evaluating the CCM intervention. We will also evaluate CCM through individual interviews and focus groups. The sample size calculation is based on a standardised effect of 0.5, and one baseline and four follow-up assessments (with correlation 0.5). Linear mixed models for repeated measures will be applied to analyse changes in quantitative outcomes over time. Multiple imputation approaches are taken to assess the robustness of the results. The explorative approach (phase ll clinical trial) with embedded qualitative research will allow for the development of a final design for a confirmative phase lll trial. ETHICS AND DISSEMINATION: The trial will be conducted under the Declaration of Helsinki and has been approved by the Ethics Commission of Cologne University's Faculty of Medicine. Trial results will be published in an open-access scientific journal and presented at conferences. TRIAL REGISTRATION NUMBER: German Register for Clinical Studies (DRKS) (DRKS00022771).

[Telemedicine assisted diet and diagnosis management in food hypersensitivity]. / Telemedizinisch unterstütztes Diät- und Diagnosemanagement bei Nahrungsmittelallergie.

Several studies have shown that the current prevalence of food allergy in Western Europe is about 4% and will further increase. Because of missing therapeutic alternatives, food allergy patients are required to identify individual allergens in the daily food by carefully reading the product's ingredient lists. Experiences with other chronic diseases show that a combination of telemedicine and Disease Management (DM) could have a positive impact on medical outcome and health related costs. A new concept of telemedicine support for allergy patients and allergists has been elaborated within the Luxembourgian MENSSANA project. Instead of measuring physiological parameters, a Smartphone based Personal Allergy Assistant (PAA) allows patients to keep an electronic patient diary by scanning the barcode of the consumed food products. For diagnostic purpose, the diary is regularly transmitted to the allergist's electronic patient record. To further support the individual diet management, the PAA gives a warning before consumption of allergenic food. Computer readable food ingredient lists are required for the PAA diet management. To collect this kind of information, a dedicated web-based "virtual community" of food consumers and producers (www.wikifood.eu) has been established. This volunteer network complements an independent product database. Up to now, more than 13.000 food descriptions are public available within wikifood.eu.

Safety and Efficacy of Crizotinib in Patients With Advanced or Metastatic ROS1-Rearranged Lung Cancer (EUCROSS): A European Phase II Clinical Trial.

INTRODUCTION: ROS1 rearrangements are found in 1% of lung cancer patients. Therapeutic efficacy of crizotinib in this subset has been shown in early phase trials in the United States and East Asia. Here we present data on efficacy and safety of a prospective phase II trial evaluating crizotinib in European ROS1-positive patients (EUCROSS). PATIENTS AND METHODS: The trial was a multicenter, single-arm phase II trial (Clinicaltrial.gov identifier: NCT02183870). Key eligibility criteria included patients who were 18 years of age or older with advanced/metastatic lung cancer and centrally confirmed ROS1-rearranged lung cancer (fluorescence-in situ hybridization). Treatment included 250 mg crizotinib twice daily. The primary endpoint was investigator-assessed objective response rate (ORR) (Response Evaluation Criteria in Solid Tumors, version 1.1). Key secondary endpoints were progression-free survival (PFS), overall survival, efficacy by independent radiologic review, safety, health-related quality of life, and molecular characterization of tumor tissue. RESULTS: Thirty-four patients received treatment. Four patients were excluded from efficacy analysis. Investigator ORR was 70% (95% confidence interval [CI]: 51-85; 21 of 30 patients) and median PFS was 20.0 months (95% CI: 10.1-not reached). Two patients with ROS1 wild-type sequences assessed by DNA sequencing had progression as best response. CD74-ROS1-positive patients had a trend towards a higher ORR and longer median PFS. TP53-co-mutant patients had a significantly shorter median PFS than wild-type patients (7.0 months, 95% CI: 1.7-20.0 versus 24.1 months, 95% CI: 10.1-not reached; p = 0.022). Treatment-related adverse events were documented in 33 of 34 patients (97%). CONCLUSIONS: Crizotinib is highly effective and safe in patients with ROS1-rearranged lung cancer. ROS1-/TP53-co-aberrant patients had a significantly worse outcome compared to TP53 wild-type patients.

Dose-finding study of carbamylated monomeric allergoid tablets in grass-allergic rhinoconjunctivitis patients.

AIM: To determine the optimal effective and safe dose of sublingual immunotherapy tablets containing carbamylated monomeric allergoids in patients with grass pollen-induced allergic rhinoconjunctivitis. METHODS: In this prospective, randomized, double-blind, active-controlled, multicenter, Phase II study, four different daily doses were applied preseasonally for 12 weeks. RESULTS: Of 158 randomized adults, 155 subjects (safety population) received 300 units of allergy (UA)/day (n = 36), 600 UA/day (n = 43), 1000 UA/day (n = 39), or 2000 UA/day (n = 37). After treatment, 54.3, 47.6, 59.0 and 51.4% of patients, respectively, ceased to react to the highest allergen concentration in a conjunctival provocation test. Furthermore, the response threshold improved in 70.4, 62.9, 76.7 and 66.7% of patients, respectively. No serious adverse events occurred. CONCLUSION: This study found 1000 UA/day to be the optimal effective and safe dose.

Glycerol lidocaine eardrops for the treatment of acute abacterial otitis externa.

Inflammations of the external auditory canal number among the most frequently occurring ear-nose-throat diseases. For local treatment, substances from various groups of active ingredients are used as combinations and as single-agent drugs, e.g. antibiotics, glucocorticoids or analgesics [1]. In the case of acute otitis externa, treatment measures focus on the reduction of pain and swelling. The study described here investigates the efficacy and safety of glycerol lidocaine eardrops for the treatment of acute abacterial otitis externa (CAS No. for glycerol: 56-81-5, lidocaine-HCl: 73-78-9). In this double-blind, three-arm study, 105 patients diagnosed with acute abacterial otitis externa were included and randomized to receive either glycerol eardrops, glycerol eardrops with 0.5% lidocaine, or glycerol eardrops with 2% lidocaine for seven days. The primary outcome parameter was the change of the five typical clinical symptoms, earache, itching, otorrhea, hearing impairment, and "clogged ear" at Visit 2 (Day 7) based on the initial examination on Day 0. Both therapy groups treated with a combination of glycerol and lidocaine exhibited definite improvement in overall symptoms after seven days. This improvement differed from the mild reduction of symptoms under treatment with glycerol eardrops alone. Overall improvement of symptoms, expressed by the area under the curve of the baseline-adjusted symptom sum score, yielded a mean value of 10.95 (standard deviation 27.4) for the morning survey of the groups receiving eardrops containing only glycerol; in comparison, for eardrops containing glycerol and 2% lidocaine it was 15.71 (+/- 23.6) and for glycerol with 0.5% lidocaine, 23.16 (+/- 19.4). No severe adverse events occurred. Five adverse events were documented during the clinical investigation, none of which was considered by the investigators to be related to the study medication. Local therapy with glycerol lidocaine eardrops is a safe, and cost-effective treatment for the widely spread clinical picture of acute abacterial otitis externa. The advantage regarding efficacy of this combination compared with glycerol eardrops must be demonstrated in an adequately powered clinical trial.