P592 Frequency and causes of prolongation of the induction course of tofacitinib in patients with ulcerative colitis in conditions of real clinical practice

Background Tofacitinib is a selective immunosuppressant, the first representative of the Janus kinase family inhibitors, which has a high selectivity against other kinases of the human genome. According to the results of the study, tofacitinib inhibits JAK-1, JAK-2 and in high concentrations-JAK-3 and tyrosine kinase-2. The drug is registered in Russia for the treatment of patients with ulcerative colitis. According to the instructions for medical use, in patients with incomplete response to the induction course, it is possible to conduct an additional 8 weeks of therapy at an induction dose of 10 mg 2 times a day. The objective of the study was to identify the frequency and reasons for the need to prolong the induction course of tofacitinib in patients with ulcerative colitis. Methods 35 patients with ulcerative colitis (UC) who received tofacitinib were observed in the Department of inflammatory bowel diseases. Patients were divided into two groups. Group 1 (n = 10) of patients were bionaive. The second group of patients (n = 25) had previous experience of treatment with one or more anti-TNF-α drugs. The necessity of prolongation up to 16 weeks of induction course of tofacitinib was assessed in patients with an insufficient clinical response at week 8 of therapy (reduction of partial index of Mayo less than 30%) and lack of normalisation of laboratory parameters (CRP, haemoglobin, FCP). The comparative analysis was carried out by the method of four-field tables using nonparametric statistical criteria. Results In the follow-up period among group 1 UC patients (n = 10) who had not previously received anti-TNF-α drugs, the need for a prolonged induction course of tofacitinib was not required in any patient (0%). In the second group of patients (n = 25), previously treated with anti-TNF-α drugs, a prolonged induction course of tofacitinib was required in 9 (36%) patients (x2-4.484; p = 0.028). Conclusion The need for prolongation up to 16 weeks of the induction course of tofacitinib in patients with ulcerative colitis b is significantly higher in patients who have previously received one or more anti-TNF-α drugs.

Acceptance of Anxiety through Art Therapy: A Case Report Exploring How Anthroposophic Art Therapy Addresses Emotion Regulation and Executive Functioning

Anxiety is a major problem for many individuals, causing impairment in daily life. Art therapy is often deployed and although positive results are communicated in clinical practice, its effectiveness and working mechanisms have hardly been studied. Therefore, it is important to systematically describe the intervention process and to detect the working mechanisms to be able to evaluate them. Narrative case studies help to understand the intervention in more depth. A typical case file was selected for case reporting according to scientific (CARE & CARE-AAT) guidelines, with the aim to explore the therapeutic elements that contributed to the reduction of anxiety. The report describes the intervention process of a 54-year-old female, suffering from anxiety since childhood and diagnosed with panic disorder, agoraphobia, claustrophobia and hypochondria. After 14 sessions of anthroposophic art therapy, reduction of anxiety was shown, as well as improvements of emotion regulation and executive functioning. The client indicated that she became more tolerant and accepting towards her anxiety. She noted a softened attitude towards herself and her complaints, even one year after art therapy. The course of treatment suggests that aspects of emotion regulation and executive functioning were addressed through implicit learning processes in different art therapy assignments.

P2873Novel ICD therapy reduction programming in primary and secondary prevention: reduced mortality and ICD-therapies in a real-life cohort

Background Implantable cardioverter defibrillator therapy (ICD), with or without combined cardiac resynchronization therapy, has been demonstrated to reduce mortality and morbidity in patients with heart failure. Nevertheless, ICD therapies are associated with increased mortality and morbidity. It was shown that ICD therapy reduction was associated with reduced event-rates. Aims It was our goal to examine a novel therapy reduction ICD programming in a real-life-cohort that also includes a notable proportion of patients with secondary prevention ICD indication. Methods Our study, based on a real-life register, contained 1013 patients. 609 patients (60%) received ICDs or CRT-Ds for secondary prevention indication. Devices implanted before May 2014 were programmed according to conventional ICD programming (CP), devices implanted since May 2014 have been programmed with a novel programming (NP) (high rate cut-off, longer detection intervals, 4 to 6 ATPs in VT-Zone). The following endpoints were analyzed for time to first event: mortality (247), appropriate therapies (248), appropriate ATPs (172), appropriate shocks (150), inappropriate therapies (102), inappropriate ATPs (49) and shocks (150). Results Middle follow-up time was 25.6 months (IQR 14.0–36.0 months) and cumulative patient years (PY) were 2165.3. According to Kaplan-Meier-analysis, there was a significant reduction in mortality-rate due NP compared to CP (19.2% vs. 30.2%, p=0.001) in the whole study population, as well as in patient subgroups with primary and secondary prevention (each p<0.05). Further, NP was associated with a reduced amount of appropriate (18.8% vs. 49.6%, p<0.001) and inappropriate therapies (5.2% vs. 21.8%, p<0.001). In Cox-regression-model, NP showed a significant reduction in mortality (HR=0.45; p=0.001) alongside history of diabetes (HR=1.35), history of chronic kidney disease (HR=1.76), reduced EF (HR=1.29) and 2nd preventional indication (HR=1.66). Further, NP was associated with a 62% reduction of appropriate and 81% reduction of inappropriate Therapies in multivariate analyses. These results were consistent after stratification for primary and secondary prevention (each p<0.05) both in Kaplan-Meier-analysis and Cox-regression-model. Regarding primary prevention, NP reduced significantly ATPs (2.7 events per 100 PY (= E/100PY) vs 16.0 E/100PY, p<0.001) as well as shocks (3.7 E/100PY vs. 8.6 E/100PY, p<0.05). Further, in secondary prevention NP was linked to a significant reduction of ATPs (11.6 E/100PY vs. 16.5E/100PY, p<0.05) and shocks (7.6 E/100PY vs. 18.0 E/100PY, p=0.001). Conclusion Novel ICD programming reduced mortality and morbidity due to appropriate or inappropriate ICD therapies independent from ICD indication. For the first time a novel ICD programming with high rate cut-off, longer detection intervals and multiple ATPs showed a benefit regarding mortality especially in patients with secondary prevention ICD indication.

CASE REPORT OF COMPLEX REHABILITATION OF PATIENT AFTER OPERATIVE TREATMENT ON THE SPINE IN CONDITIONS OF SANATORIUM WITH USE OF KINESOTHERAPY

The clinical case of the patient after operational treatment of a backbone and a rehabilitation course in the conditions of a day hospital is described. For assessment of efficiency of the held events pain scales YOURS, Rivermead Motor Assessment Scale were used. The program of a rehabilitation for by classical techniques of treatment included reflexotherapy methods with pharmakopunktura, trainings on the system of "Ekzart", electrostimulation. The patient received 2 rehabilitation courses: in 3 and 5 months after operational treatment, as a result of the executed treatment, at the patient at control survey from the moment of the beginning of therapy reduction of a pain syndrome, increase in independent daily activity, increase in insistence, normalization of indicators of the mental status is noted. The first rehabilitation course allowed to adapt the patient to house conditions, and returned her a possibility of partial self-service. The second year of rehabilitation set the reached effect and allowed the patient to move independently out of the room that significantly increased her standard of living. On the term of 4 months after an operative measure on a backbone at the patient the pain syndrome and restriction of life activity remained. The held complex of rehabilitation actions after backbone operation significantly improved indicators of quality of life and functional independence of rather initial level that speaks about its efficiency in ensuring earlier social reintegration of the patient.

CASE REPORT OF COMPLEX REHABILITATION OF PATIENT AFTER OPERATIVE TREATMENT ON THE SPINE IN CONDITIONS OF SANATORIUM WITH USE OF KINESOTHERAPY

The clinical case of the patient after operational treatment of a backbone and a rehabilitation course in the conditions of a day hospital is described. For assessment of efficiency of the held events pain scales YOURS, Rivermead Motor Assessment Scale were used. The program of a rehabilitation for by classical techniques of treatment included reflexotherapy methods with pharmakopunktura, trainings on the system of "Ekzart", electrostimulation. The patient received 2 rehabilitation courses: in 3 and 5 months after operational treatment, as a result of the executed treatment, at the patient at control survey from the moment of the beginning of therapy reduction of a pain syndrome, increase in independent daily activity, increase in insistence, normalization of indicators of the mental status is noted. The first rehabilitation course allowed to adapt the patient to house conditions, and returned her a possibility of partial self-service. The second year of rehabilitation set the reached effect and allowed the patient to move independently out of the room that significantly increased her standard of living...

THE GENESE OF PREDICTIVE-PERSONIFIED MEDICINE AND THE PROBLEMS OF ITS IMPLEMENTATION IN UKRAINE

The concepts, content and significance of predictive-personified medicine that are able to improve the quality of treatment, using genetic information when choosing the medical procedures that are necessary for a particular person are considered. Characteristic of the principles of predictive-personified medicine and its fundamental foundations are carried out: genomics; proteomics; metabolism; bioinformatics The history of the formation and development of predictive-personified medicine in the world is investigated, the relevant legal documents are analyzed. The main advantages of predictive-personified medicine are determined: detection of an illness at an earlier stage, when its treatment is more efficient and cheaper; division of patients into similar groups for the choice of optimal therapy; reduction of adverse reactions to drugs by more effective early assessment of individual negative reactions; improvement of the selection of new biochemical indicators, allowing to control the action of medicinal products; reducing the time, cost, and the number of failures in clinical trials of new treatments. It is noted that in Ukraine none of the well-known projects approved by the American and European committees on gene therapy are implemented. However, the priority direction of research in the field of genetics is chosen annually by more and more medical institutions of Ukraine. Examples of the introduction of predictive-personified medicine into medical institutions and scientific institutes in Ukraine are presented. It is concluded that ensuring the effectiveness of this direction of modern medicine depends on the elimination of many problems of socio-managerial and regulatory nature. In addition to their solution, the priority tasks in this area include the carrying out of significant informational and enlightening work with the population; increase of state funding for the development of preventive medicine; creation of public-private partnership of base centers.

Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study

Key Points Early introduction of cyclosporine did not improve HLH outcome in patients treated with the HLH-94 etoposide-dexamethasone backbone (P = .06). HLH-2004 may be improved by risk-group stratification, less therapy reduction weeks 7 to 8 for verified FHL patients, and earlier HSCT.

Therapy reduction in patients with Down syndrome and myeloid leukemia: the international ML-DS 2006 trial

Key Points Reducing therapy intensity in the ML-DS 2006 trial did not impair the excellent prognosis in ML-DS compared with the historical control. Early treatment response and gain of chromosome 8 are independent prognostic factors.

Glucocorticoid therapy and adrenal suppression

Introduction. Adrenal insufficiency results from the inadequate adrenocortical conjunction. Adrenal insufficiency can be primary, secondary and tertiary one. The most common cause of adrenal suppression is the effect of exogenous therapy with glucocorticoids. Glucocorticoids. Corticosteroids are used in treatment of endocrine and non-endocrine diseases. They are applied as a substitution therapy in the patients with primary and secondary adrenal insufficiency. Due to their immunosuppressive and anti-inflammatory characteristics, they are used to treat a wide range of diseases. They are usually divided according to the length and size of the effect i.e. how they are applied. Adrenal Insufficiency. Glucocorticoid therapy may lead to a number of adverse effects such as a disorder in glucose metabolism, osteoporosis or frequent infections. Adrenal suppression is the most common complication resulting from corticosteroid application. The function of the hypothalamus-pituitary-adrenal axis may be inhibited for months after the treatment cessation. There are several predictors of potential glucocorticoid-induced adrenal suppression. Diagnosing Adrenal Insufficiency. The most frequent symptoms and signs of adrenal insufficiency are fatigue, nausea and vomiting, hyponatremia, hyperpigmentation or hypotension. Algorithm for the diagnosis of adrenal insufficiency must be followed in clinical practice. Reduction in Glucocorticoid Therapy. Reduction or complete cessation of the therapy is indicated when the maximum therapeutic benefit has been achieved or when considerable side effects, such as diabetes mellitus, severe hypertension, osteoporosis i.e. adrenal insufficiency, develop. Conclusion. Numerous synthetic glucocorticoids have been developed to be used in everyday clinical practice and they can be administered systemically or locally. A lot of side effects are associated with chronic administration of glucocorticoids. In order to avoid complications, it is recommended to administer intermediate-acting glucocorticoids every second day. In addition, the patients must be monitored carefully and glucocorticoid therapy should be discontinued gradually to prevent adrenal insufficiency or reactivation of the disease under therapy.

Omalizumab reduces bronchial mucosal IgE and improves lung function in non-atopic asthma

Omalizumab therapy of non-atopic asthmatics reduces bronchial mucosal IgE and inflammation and preserves/improves lung function when disease is destabilised by staged withdrawal of therapy.18 symptomatic, non-atopic asthmatics were randomised (1:1) to receive omalizumab or identical placebo treatment in addition to existing therapy for 20 weeks. Bronchial biopsies were collected before and after 12–14 weeks of treatment, then the patients destabilised by substantial, supervised reduction of their regular therapy. Primary outcome measures were changes in bronchial mucosal IgE+ cells at 12–14 weeks, prior to regular therapy reduction, and changes in lung function (forced expiratory volume in 1 s) after destabilisation at 20 weeks. Quality of life was also monitored.Omalizumab but not placebo therapy significantly reduced median total bronchial mucosal IgE+ cells (p<0.01) but did not significantly alter median total mast cells, plasma cells, B lymphocytes, eosinophils and plasmablasts, although the latter were difficult to enumerate, being distributed as disperse clusters. By 20 weeks, lung function declined in the placebo-treated patients but improved in the omalizumab treated patients, with significant differences in absolute (p=0.04) and % predicted forced expiratory volume in 1 s (p=0.015).Omalizumab therapy of non-atopic asthmatics reduces bronchial mucosal IgE+ mast cells and improves lung function despite withdrawal of conventional therapy.