Infection control, genetic assessment of drug resistance and drug susceptibility testing in the current management of multidrug/extensively-resistant tuberculosis (M/XDR-TB) in Europe: A tuberculosis network European Trialsgroup (TBNET) study

Aim Europe has the highest documented caseload and greatest increase in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) of all World Health Organization (WHO) regions. This survey examines how recommendations for M/XDR-TB management are being implemented. Methods TBNET is a pan-European clinical research collaboration for tuberculosis. An email survey of TBNET members collected data in relation to infection control, access to molecular tests and basic microbiology with drug sensitivity testing. Results 68/105 responses gave valid information and were from countries within the WHO European Region. Inpatient beds matched demand, but single rooms with negative pressure were only available in low incidence countries; ultraviolet decontamination was used in 5 sites, all with >10 patients with M/XDR-TB per year. Molecular tests for mutations associated with rifampicin resistance were widely available (88%), even in lower income and especially in high incidence countries. Molecular tests for other first line and second line drugs were less accessible (76 and 52% respectively). A third of physicians considered that drug susceptibility results were delayed by > 2 months. Conclusion Infection control for inpatients with M/XDR-TB remains a problem in high incidence countries. Rifampicin resistance is readily detected, but tests to plan regimens tailored to the drug susceptibilities of the strain of Mycobacterium tuberculosis are significantly delayed, allowing for further drug resistance to develop

COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study

Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72–14·87; p=0·0035), male sex (2·12, 1·06–4·21; p=0·033), pre-existing medical conditions (3·27, 1·67–6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16–21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir–ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20–1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. Funding ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit

Diagnostic relationnel établi sur la base du DPO pour enfants et adolescents

Traditionelle psychodynamische Diagnostik basiert auf dem szenischen Verstehen innerhalb des Erstkontaktes mit einem Patienten. Beziehungsdiagnostik ist sie insoweit, als Übertragungs- und Gegenübertragungsphänomene für die Einschätzung eine zentrale Rolle spielen. Solche Diagnosen schließen Hypothesen über Krankheitsursachen mit ein, sind tendenziell eher ungenau und kaum vergleichbar. Phänomenologische psychiatrische Diagnosekonzepte wie die ICD-10 zielen durch „Theoriefreiheit“ auf methodenübergreifende Anwendbarkeit, bleiben für eine psychodynamische Denkweise und Therapieplanung aber eher unbefriedigend. Mit der Operationalisierten Psychodynamischen Diagnostik für Erwachsene (OPD-E) ist als Alternative und Ergänzung ein Diagnosesystem entwickelt worden, in dem psychodynamische Theoriekonzepte deskriptiv operationalisiert worden sind. Im Kindes- und Jugendalter ist ein eigenes psychodynamisches Instrument erforderlich. Die vor der Erprobung stehende Operationalisierte Psychodynamische Diagnostik für Kinder und Jugendliche (OPD-KJ) wird in ihren Grundzügen und den Besonderheiten bei Kindern und Jugendlichen skizziert. Die eingehender beschriebene Achse II (Beziehungsachse) erfasst sowohl dyadische als auch triadische Beziehungsmuster und Beziehungsqualitäten in standardisierter Weise. Ihre besondere Bedeutung ergibt sich nicht zuletzt aus Befunden der Psychotherapieforschung und der Notwendigkeit qualitätssichernder Maßnahmen in der Psychotherapie. Schlüsselwörter: Psychodynamische Diagnostik, Psychoanalyse, Operationalisierung, Kinder und Jugendliche, BeziehungsachseTraditional psychodynamic diagnostics is based on scenic understanding in the course of the first session with a patient. With transference and countertransference phenomena playing a key role in the assessment process, it is a diagnosis of human relationships. These diagnoses are characterized by including hypotheses on etiology, being rather rough and lacking a standardized form. Diagnostic systems used in psychiatry such as the ICD-10, which are based on phenomenology to ensure wide applicability regardless of theoretical backgrounds, have remained unsatisfactory for the purposes of psychodynamic thinking and therapy planning. Developed as an alternative and supplementary diagnostic system, the Operationalized Psychodynamic Diagnostics for Adults (OPD-E) operationalizes psychodynamic concepts in a descriptive manner. For use with children and adolescents an additional version had to be developed and is about to be evaluated. The Operationalized Psychodynamic Diagnostics for Children and Adolescents (OPD-KJ) is briefly described in general terms and with reference to particular features of the KJ-version. Axis II (relationship axis), which assesses dyadic and triadic relational patterns and qualities in a standardized manner, is described in more detail. Its particular relevance may be concluded from psychotherapy research findings and the necessity of quality assurance.Keywords: Psychodynamic diagnostics, psychoanalysis, operationalization, children and adolescents, relationship axisEn psychanalyse et en psychologie des profondeurs le diagnostic se fonde traditionnellement sur la première interview, à savoir sur une perception scénique dans le cadre d’un premier contact avec le patient, y compris certaines hypothèses concernant l’origine de ses troubles. Il est ‘relationnel’ dans le sens où transfert et contre-transfert jouent un rôle central par rapport à l’évaluation. Le manque de précision des concepts psychanalytiques impliqués et le fait que les diagnostics fondés sur ces derniers sont mal comparables ont provoqué la critique des scientifiques et des assureurs. En psychiatrie des instruments ont été créés - l’ICD-10 par exemple -, qui correspondent à des concepts descriptifs basés sur une approche phénoménologique ; ils sont considérés comme applicables par rapport à toutes les méthodes puisqu’ils visent à exclure les présupposés étiologiques ou théoriques. U reste que les psychothérapeutes utilisant une approche psychodynamique n’y retrouvent pas leur démarche spécifique. Le ’diagnostic psychodynamique opérationnalisé pour adultes’ (OPD-E en allemand) est un instrument qui a été développé et testé en tant qu’alternative et que complément, incluant une opérationnalisation descriptive des concepts théoriques relevant d’une approche psychodynamique. Or, il n’est pas applicable tel quel aux enfants et adolescents, leur cas requérant un instrument spécifique. Un DPO (OPD-KJ) à utiliser pour des patients enfants ou adolescents est actuellement en phase de test; il est présenté ici, avec ses quatre axes psychodynamiques (manière dont les troubles sont vécus, relation, conflit et structure) ainsi que les particularités trouvées dans le cas d’enfants et d’adolescents. Les points faibles méthodiques du diagnostic psychanalytique traditionnel sont mis en évidence, ainsi que l’importance particulière de l’aspect relationnel dans le cadre d’une psychothérapie utilisant une approche psychodynamique. L’axe II (relation) est présenté en détail. U comprend des schémas relationnels standardisés de types dyade et triade, aussi bien qu’une caractérisation des qualités de la relation.Un modèle circulaire en rapport avec les schémas relationnels dyadiques décrit les aspects qualité émotionnelle (entre les pôles hostile vs. affectueux) et champ, soit structure de la relation (pôles: contrôle vs. autonomie) liant l’enfant à des personnes définies. Est également incluse une évaluation de la résonance de l’explorateur sur le patient, ainsi que celle d’interlocuteurs spécifiques ou de sa famille. Ceci permet de saisir les phénomènes de contre-transfert perceptibles et de les prendre en compte au moment de formuler le diagnostic.Le modèle concernant les schémas relationnels triadiques décrit les échanges réciproques au niveau de leur tonalité émotionnelle (ici encore l’axe horizontal comporte en ses extrémités les pôles hostile/affectueux) et de la qualité des interactions (flexibilité ou rigidité d’une triade donnée sur l’axe vertical). Ce système permet de distinguer une triade flexible, mais non arbitraire, d’une triade rigide ou d’un système triadique en voie de désagrégation, dans lequel une personne s’exclut elle-même ou est exclue par les autres. Il tient compte de la structure familiale, qui joue un rôle important dans le contexte du diagnostic des enfants et adolescents.L’attention particulière portée à l’axe relationnel se justifie en particulier sur la base de résultats acquis par la recherche en psychothérapie et de la nécessité d’établir des mesures visant à garantir la qualité de ses traitements

Subclinical leaflet thrombosis after transcatheter aortic valve replacement : a meta-analysis

This meta-analysis and systematic review was performed to evaluate the clinical relevance of subclinical leaflet thrombosis (SLT) following transcatheter aortic valve replacement. PubMed, Web of Science, and CENTRAL were searched for eligible randomized and nonrandomized studies until November 2020. Risk ratios (RRs) or odds ratios and 95% CIs were calculated, using a random-effects model. Overall, 25 studies were eligible for the analysis and comprised a total of 11,098 patients. The median incidence of SLT was 6% at a median follow-up of 30 days. Use of intra-annular valves was associated with 2-fold greater risk for the development of SLT compared with use of supra-annular valves. There was no difference in the risk for SLT (RR: 0.97; 95% CI: 0.72-1.29; P = 0.83) between single-antiplatelet therapy (SAPT) and dual-antiplatelet therapy (DAPT), whereas oral anticoagulation (OAC) was associated with a 58% relative risk reduction for SLT (RR: 0.42; 95% CI: 0.29-0.61; P < 0.00001) compared with SAPT and DAPT. In patients with diagnosed leaflet thrombosis at follow-up, the risk for stroke or transient ischemic attack was increased by 2.6-fold (RR: 2.56; 95% CI: 1.60-4.09; P < 0.00001) compared with patients without leaflet thrombosis. In patients diagnosed with SLT, the odds of SLT resolution increased by 99% after switch from antiplatelet agents to OAC (odds ratio: 0.01; 95% CI: 0.00-0.06; P < 0.00001). To summarize, indication-based use of OAC after transcatheter aortic valve replacement is associated with a lower risk for SLT compared with SAPT and DAPT. Switching to OAC seems to be effective for SLT resolution. As SLT increased the odds of stroke or transient ischemic attack in the included population, further studies are needed to investigate whether screening tests for SLT and appropriate antithrombotic therapy improve long-term valve functionality and clinical prognosis

COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study

Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72–14·87; p=0·0035), male sex (2·12, 1·06–4·21; p=0·033), pre-existing medical conditions (3·27, 1·67–6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16–21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir–ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20–1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed

Consensus-Based Guidelines for Diagnosis, Prevention and Treatment of Tuberculosis in Children and Adolescents

Recently, epidemiological data shows an increase of childhood tuberculosis in Germany. In addition to this, drug resistant tuberculosis becomes more frequent. Therefore, diagnosis, prevention and therapy in childhood and adolescence remain a challenge. Adult guidelines do not work for children, as there are age specific differences in manifestation, risk of progression and diagnostic as well as therapeutic pathways. The German Society for Pediatric Infectious Diseases (DGPI) has initiated a consensus-based (S2k) process and completed a paediatric guideline in order to improve and standardize care for children and adolescents with tuberculosis exposure, infection or disease. Updated dosage recommendations take age dependant pharmacokinetics in the treatment of drug sensitive but also drug resistant tuberculosis in account. In addition to this, there is a detailed chapter on perinatal exposure and disease as well as extrapulmonary manifestations

COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study

Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72–14·87; p=0·0035), male sex (2·12, 1·06–4·21; p=0·033), pre-existing medical conditions (3·27, 1·67–6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16–21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir–ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20–1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed. Funding ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit

Tuberculosis disease in children and adolescents on therapy with antitumor necrosis factor - A agents: A collaborative, multicenter paediatric tuberculosis network European Trials Group (ptbnet) Study

Background. In adults, anti–tumor necrosis factor-α (TNF-α) therapy is associated with progression of latent tuberculosis (TB) infection (LTBI) to TB disease, but pediatric data are limited. Methods. Retrospective multicenter study within the Paediatric Tuberculosis Network European Trials Group, capturing patients <18 years who developed TB disease during anti–TNF-α therapy. Results. Sixty-six tertiary healthcare institutions providing care for children with TB participated. Nineteen cases were identified: Crohn’s disease (n = 8; 42%) and juvenile idiopathic arthritis (n = 6; 32%) were the commonest underlying conditions. Immune-based TB screening (tuberculin skin test and/or interferon-γ release assay) was performed in 15 patients before commencing anti–TNF-α therapy but only identified 1 LTBI case; 13 patients were already receiving immunosuppressants at the time of screening. The median interval between starting anti–TNF-α therapy and TB diagnosis was 13.1 (IQR, 7.1–20.3) months. All cases presented with severe disease, predominantly miliary TB (n = 14; 78%). One case was diagnosed postmortem. TB was microbiologically confirmed in 15 cases (79%). The median duration of anti-TB treatment was 50 (IQR, 46–66) weeks. Five of 15 (33%) cases who had completed TB treatment had long-term sequelae. Conclusions. LTBI screening is frequently false-negative in this patient population, likely due to immunosuppressants impairing test performance. Therefore, patients with immune-mediated diseases should be screened for LTBI at the point of diagnosis, before commencing immunosuppressive medication. Children on anti–TNF-α therapy are prone to severe TB disease and significant long-term morbidity. Those observations underscore the need for robust LTBI screening programs in this high-risk patient population, even in low-TB-prevalence settings