Chronicity and sensory-clinical phenotyping of musculoskeletal pain syndromes

The dissertation investigated the differentiation of subsyndromes in a spectrum from regional to widespread chronic musculoskeletal pain on the basis of mechanism-related somatosensory and clinical phenotypes within the framework of the multidimensional model of chronic pain. The first study analyzed the dimensional structure of the chronicity construct and its necessary and sufficient components. The second study identified discriminable pain-related phenotypes in two exemplary syndromes of chronic musculoskeletal pain by a stepwise cluster-analytic approach and related these to secondary comorbidity and psychosocial factors. In the first study, diagnostic entrance data of 185 patients with chronic regional vs. widespread musculoskeletal pain (unspecific back pain, fibromyalgia syndrome) from regional pain clinics and of 170 active employees in a nationwide prevention program were included in a retrospective cross-sectional analysis to reanalyze the construct of chronicity. The marker sets of three established chronicity indices (IASP Pain Taxonomy Axis IV, Chronic Pain Grade, Mainz Pain Staging System) were reanalyzed by correlations and frequency distributions of successive duration classes. Factor and latent class analyses were applied to assess the dimensional structure of pain and chronicity. Pain intensity distributions showed inhomogeneous courses from short to long durations differing between groups. Both dimensions, pain intensity and duration, related unsystematically to CPG and MPSS. Different dimensions and clusters of chronicity markers were discovered, that differed between the groups (three dimensions and clusters in patients, two dimensions and clusters in employees). In fact, there was evidence for at least three weakly coupled core domains of chronicity, i.e., the primary clinical pain characteristics, the direct consequences of current interference with activities and aspects of the patient history (duration and health care utilization). In the second study, the sensory and clinical characteristics of the patient sample were reanalyzed to identify necessary and sufficient markers differentiating subsyndromes with different sensory-clinical phenotypes along the continuum from regionally confined to extensively widespread pain. For this purpose, 107 chronic unspecific back pain patients and 78 patients with fibromyalgia syndrome were taken as exemplary instantiations with circumscribed diagnoses. Four clusters of differential sensory-clinical phenotypes covering a spectrum from regional to widespread pain were discovered on the basis of four pressure pain sensitivity markers (number of sensitive ACR tender and control points, test pain intensity and pressure pain threshold) and two clinical pain markers (number of pain regions, present pain intensity). A consecutive discriminant analysis showed that the pressure sensitivity markers alone sufficed already to discriminate between the clusters with a high correct rate. The sensory-clinical phenotypes differed also in other somatic symptoms and impairment but not in psychopathology nor in psychosocial co-factors. The project showed that differential diagnostics of chronic musculoskeletal pain requires at least a multifactorial determination of its chronicity with respect to the necessary components of duration, severity and impairment and the identification of the individual pain phenotype by comprehensive sensory and clinical assessment. This is considered as the prerequisite of differential indication of specific modules in multimodal pain therapy to avoid unselective polypragmasia

Generation of human antibody fragments against Streptococcus mutans using a phage display chain shuffling approach

BACKGROUND: Common oral diseases and dental caries can be prevented effectively by passive immunization. In humans, passive immunotherapy may require the use of humanized or human antibodies to prevent adverse immune responses against murine epitopes. Therefore we generated human single chain and diabody antibody derivatives based on the binding characteristics of the murine monoclonal antibody Guy's 13. The murine form of this antibody has been used successfully to prevent Streptococcus mutans colonization and the development of dental caries in non-human primates, and to prevent bacterial colonization in human clinical trials. RESULTS: The antibody derivatives were generated using a chain-shuffling approach based on human antibody variable gene phage-display libraries. Like the parent antibody, these derivatives bound specifically to SAI/II, the surface adhesin of the oral pathogen S. mutans. CONCLUSIONS: Humanization of murine antibodies can be easily achieved using phage display libraries. The human antibody fragments bind the antigen as well as the causative agent of dental caries. In addition the human diabody derivative is capable of aggregating S. mutans in vitro, making it a useful candidate passive immunotherapeutic agent for oral diseases

Автоматизированная информационно-библиотечная система «Библиобус»: современная версия

The article is devoted to the work of the automated information library system (AILS) “Bibliobus”, developed by specialists of the Library for Natural Sciences of the Russian Academy of Sciences (LNS RAS). The purpose of this article is to acquaint readers of the journal with the specific features of the modern AILS “Bibliobus” that provides complex automation of the main technological processes on the “way of book” of non-periodicals received in the centralized library system (CLS) holdings of LNS RAS. The authors describe capability features and functions of the system, the rules of work with it, the user interface for performing work related to centralized acquisition, book registration and distribution of the incoming books between the CLS libraries, cataloguing, classifying, etc. The system has a number of features that distinguish it from most automated library systems. It is focused on the centralized library network; part of the information is entered in the Centre, part — interactively in the libraries of the network; all the accounting and financial documents required by the centralized system are generated automatically. The AILS “Bibliobus” widely uses the bar coding, it applies to all stages of publication processing on the “way of book”; the bar codes appear on all supporting documents and printed cards. When cataloguing the publications, bibliographer introduces in the main “window” of system the bibliographic description in the format of State Standard GOST 7.1—2003 with some mark-ups, and in additional “windows” — the maximum possible metadata, providing multi-aspect search of the publication in the catalogue; the search fields for e-catalogue are generated automatically. The AILS “Bibliobus” provides for the formation of multi-level records. Its database stores the images of scanned text pages displayed in the electronic catalogue; all operations are logged with the start and end time, which allowed building on its basis a powerful reference and statistical system. The system has a modern user interface that allows the operator to obtain multiple information on various aspects of technological operations.Статья посвящена работе автоматизированной информационно-библиотечной системы (АИБС) «Библиобус», разработанной специалистами Библиотеки по естественным наукам Российской академии наук (БЕН РАН). Цель статьи — познакомить читателей журнала с особенностями современной АИБС «Библиобус», обеспечивающей комплексную автоматизацию основных технологических процессов по «пути книги» непериодических изданий, поступающих в фонды ЦБС БЕН РАН. Описываются возможности и функции системы, правила работы с ней, пользовательский интерфейс при выполнении работ, связанных с централизованным комплектованием, регистрацией поступлений и распределением поступающих книг между библиотеками ЦБС, каталогизацией, систематизацией и т. д. Система имеет ряд особенностей, отличающих ее от большинства автоматизированных библиотечных систем. Она ориентирована на централизованную библиотечную сеть, часть информации вводится в центре, часть — в библиотеках сети в интерактивном режиме; все необходимые для централизованной системы учетно-финансовые документы формируются автоматически. В АИБС «Библиобус» широко используется штрих-кодирование — оно применяется на всех этапах обработки издания по «пути книги», штрих-коды выводятся на все сопроводительные документы и на печатные карточки. При каталогизации изданий библиограф вводит в основное «окно» системы библиографическое описание в формате ГОСТ 7.1—2003 с некоторой разметкой, а в дополнительные «окна» — максимально возможное количество метаданных, обеспечивающих многоаспектный поиск издания в каталоге; поисковые поля для электронного каталога формируются автоматически. АИБС «Библиобус» предусматривает формирование многоуровневых записей. В ее базе данных хранятся образы отсканированных страниц текста, выводимые в электронный каталог; протоколируются все операции с указанием времени начала и конца, что позволило построить на ее основе мощную справочно-статистическую систему. Система обладает современным пользовательским интерфейсом, позволяющим оператору получать информацию по различным аспектам технологических операций

Cost-effectiveness of tipranavir versus comparator protease inhibitor regimens in HIV infected patients previously exposed to antiretroviral therapy in the Netherlands

<p>Abstract</p> <p>Background</p> <p>This study compares the costs and effects of a regimen with ritonavir-boosted tipranavir (TPV/r) to a physician-selected genotypically-defined standard-of-care comparator protease inhibitor regimen boosted with ritonavir (CPI/r) in HIV infected patients that were previously exposed to antiretroviral therapy in the Netherlands.</p> <p>Methods</p> <p>We compared the projected lifetime costs and effects of two theoretical groups of 1000 patients, one receiving a standard of care regimen with TPV/r as a component and the other receiving a standard of care regimen with CPI/r. A 3-stage Markov model was formulated to represent three different consecutive HAART regimens. The model uses 12 health states based on viral load and CD4+ count to simulate disease progression. The transition probabilities for the Markov model were derived from a United States cohort of treatment experienced HIV patients. Furthermore, the study design was based on 48-week data from the RESIST-2 clinical trial and local Dutch costing data. Cost and health effects were discounted at 4% and 1.5% respectively according to the Dutch guideline. The analysis was conducted from the Dutch healthcare perspective using 2006 unit cost prices.</p> <p>Results</p> <p>Our model projects an accumulated discounted cost to the Dutch healthcare system per patient receiving the TPV/r regimen of €167,200 compared to €145,400 for the CPI/r regimen. This results in an incremental cost of €21,800 per patient. The accumulated discounted effect is 7.43 life years or 6.31 quality adjusted life years (QALYs) per patient receiving TPV/r, compared to 6.91 life years or 5.80 QALYs per patient receiving CPI/r. This translates into an incremental effect of TPV/r over CPI/r of 0.52 life years gained (LYG) or 0.51 QALYs gained. The corresponding incremental cost effectiveness ratios (iCERs) are €41,600 per LYG and €42,500 per QALY.</p> <p>Conclusion</p> <p>We estimated the iCER for TPV/r compared to CPI/r at approximately €40,000 in treatment experienced HIV-1 infected patients in the Netherlands. This ratio may well be in range of what is acceptable and warrants reimbursement for new drug treatments in the Netherlands, in particular in therapeutic areas as end-stage oncology and HIV and other last-resort health-care interventions.</p

PARE0009 COMMUNITY ADVISORY BOARD INPUT CAN MAKE LAY SUMMARIES OF CLINICAL TRIAL RESULTS MORE UNDERSTANDABLE

Background:Under European Union (EU) Clinical Trial regulations,1clinical research sponsors (CRSs) must ensure all studies performed in the EU are accompanied by a trial summary for laypersons, published within 1 year of study completion. These lay summaries should disseminate clinical trial results in an easy-to-understand way for trial participants, patient and caregiver communities, and the general public. The European Patients Forum (EPF)2and European Patients' Academy on Therapeutic Innovation (EUPATI)3encourage CRSs to engage with patient organisations (POs) in the development of lay summaries. This recognises the patients' contribution to clinical research and supports the development of patient-focused material.Objectives:We share learnings from a collaboration between scleroderma POs and a CRS to create the SENSCIS® trial (NCT02597933) written and video lay summaries.Methods:A community advisory board (CAB), comprising representatives from 11 scleroderma POs covering a range of countries/regions, was formed based on the EURORDIS charter for collaboration in clinical research.4Through three structured meetings, over a seven-month period, the CAB provided advice on lay summary materials (written and video) drafted by the CRS' Lay Summary Group (Fig. 1). At each review cycle, the CAB advice was addressed to make content more understandable and more relevant for patients and the general public.Results:The CAB advised that the existence of lay summaries is not well known in the patient community and also recommended the development of trial-specific lay summary videos to further improve understandability of the clinical trial results for the general public. Videos are a key channel of communication, enabling access to information for people with specific health needs and lower literacy levels. Following CAB advice, the CRS developed a stand-alone video entitled"What are lay summaries?"and a trial-specific lay summary video. Revisions to lay summary content (written and video) included colour schemes, iconography and language changes to make content more understandable. For videos, adjustments to animation speed, script and voiceover were implemented to improve clarity and flow of information (Fig. 2). Approved final versions of lay summary materials are publicly available on the CRS website. Translation into languages representing trial-site countries is in progress to widen access to non-English speakers and, where possible, local versions are being reviewed by the patient community.Conclusion:Structured collection and implementation of CAB advice can make lay summary materials more understandable for the patient community and wider general public.References:[1]EU. Summaries of clinical trial results for laypersons. 2018[2]EPF. EPF position: clinical trial results – communication of the lay summary. 2015[3]EUPATI. Guidance for patient involvement in ethical review of clinical trials. 2018[4]EURORDIS. Charter for Collaboration in Clinical Research in Rare Diseases. 2009Disclosure of Interests:Joep Welling Speakers bureau: Four times as a patient advocate for employees of BII and BI MIDI with a fixed amount of € 150,00 per occasion., Annelise Roennow: None declared, Maureen Sauvé Grant/research support from: Educational grants from Boehringer Ingelheim and Janssen., EDITH BROWN: None declared, Ilaria Galetti: None declared, Alex Gonzalez Consultant of: Payment made to the patient organisation (Scleroderma Research Foundation) for participation in advisory boards, Alexandra Paula Portales Guiraud: None declared, Ann Kennedy Grant/research support from: AS FESCA aisbl, Catarina Leite: None declared, Robert J. Riggs: None declared, Alison Zheng Grant/research support from: We get grants from Lorem Vascular; BI China,; Jianke Pharmaceutical Co., Ltd.; Kangjing Biological Co., Ltd.; COFCO Coca-Cola to organize national scleroderma meetings, offer patients service, holding academic meetings and other public activities, there is also a small part of the grants used to pay the workers in our organization., Consultant of: I worked as a paid consultant for BI. Pay-per-job., Speakers bureau: I was invited once to be a speaker at BI China's internal meeting and they paid me., Matea Perkovic Popovic: None declared, Annie Gilbert Consultant of: I have worked as a paid consultant with BI International for over 3 years, since Sept 2016., Lizette Moros Employee of: Lizette Moros is an employee of Boehringer Ingelheim, Kamila Sroka-Saidi Employee of: Paid employee of Boehringer Ingelheim., Thomas Schindler Employee of: Employee of Boehringer Ingelheim Pharma, Henrik Finnern Employee of: Paid employee of Boehringer Ingelheim