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186 results on '"Simon Tiberi"'

1. Expert views on screening for tuberculosis infection in patients commencing treatment with a biologic agent

Author: Adiba Sultana, Giovanni Battista Migliori, Lia D’Ambrosio, José-María García-García, Denise Rossato Silva, Luis Adrian Rendon, Luigi R Codecasa, Francois-Xavier Blanc, Simon Tiberi, Catherine W M Ong, Courtney Heffernan, Giovanni Sotgiu, Rosella Centis, and Claudia Caroline Dobler
Subjects: Latent tuberculosis, Biological products, Immunosuppression therapy, Recurrence, Mass screening, Diseases of the respiratory system, RC705-779
Abstract: ABSTRACT Objective: Many biologic agents cause some degree of immunosuppression, which can increase the risk of reactivation of tuberculosis infection (TBI). This risk is variable between individual biologics. We aimed to assess current (and recommended) clinical practice of TBI screening and treatment among patients initiating treatment with biologic agents. Methods: An online questionnaire was distributed via email to members of the Global Tuberculosis Network and associated professional organisations to seek insights into the screening for and treatment of TBI in patients treated with biologics. Results: A total of 163 respondents in 27 countries answered at least one question. For all biologics described in the questionnaire, respondents advised increasing screening relative to current practice. Observed and supported TBI screening rates in patients treated with TNF-a inhibitors were high, especially for older TNF-a inhibitors. Most participants supported TBI screening in patients treated with B- or T-cell inhibitors but not in those treated with interleukin inhibitors. Guideline awareness was higher for TNF-a inhibitors than for other biologic classes (79% vs. 34%). Conclusions: Although respondents stated that TBI screening rates are lower than what they consider ideal, there was a tendency to recommend TBI screening in patients treated with biologics not known to be associated with an increased risk of TBI. As a result, there is a potential risk of over-screening and over-treatment of TBI, potentially causing harm, in patients treated with biologics other than TNF-a inhibitors. There is a need to research the risk of TBI associated with biologics and for guidelines to address the spectrum of TBI risk across all types of biologics.
Published: 2024
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2. Efficacy of three antimicrobial mouthwashes in reducing SARS-CoV-2 viral load in the saliva of hospitalized patients: a randomized controlled pilot study

Author: Jeniffer Perussolo, Muy-Teck Teh, Nikolaos Gkranias, Simon Tiberi, Aviva Petrie, Maria-Teresa Cutino-Moguel, and Nikolaos Donos
Subjects: Medicine, Science
Abstract: Abstract This study aimed to evaluate the efficacy of 3 mouthwashes in reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in the saliva of coronavirus disease 2019 (COVID-19) patients at 30 min, 1, 2 and 3 h after rinsing. This pilot study included 40 admitted COVID-19 positive patients (10 in each group). Saliva samples were collected before rinsing and at 30 min, 1, 2 and 3 h after rinsing with: Group 1—0.2% Chlorhexidine digluconate (CHX); Group 2—1.5% Hydrogen peroxide (H2O2); Group 3—Cetylpyridinium chloride (CPC) or Group 4 (control group)—No rinsing. Viral load analysis of saliva samples was assessed by Reverse Transcription quantitative PCR. Mean log10 viral load at different time points was compared to that at baseline in all groups using a random effects linear regression analysis while for comparison between groups linear regression analysis was used. The results showed that all groups had a significantly reduced mean log10 viral load both at 2 (p = 0.036) and 3 (p = 0.041) hours compared to baseline. However, there was no difference in mean log10 viral load between any of the investigated mouthwashes and the control group (non-rinsing) at the evaluated time points. Although a reduction in the SARS-CoV-2 viral load in the saliva of COVID-19 patients was observed after rinsing with mouthwashes containing 0.2% CHX, 1.5% H2O2, or CPC, the reduction detected was similar to that achieved by the control group at the investigated time points. The findings of this study may suggest that the mechanical action of rinsing/spitting results in reduction of SARS-CoV-2 salivary load.
Published: 2023
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3. Update of drug-resistant tuberculosis treatment guidelines: A turning point

Author: Elisa Vanino, Bianca Granozzi, Onno W. Akkerman, Marcela Munoz-Torrico, Fabrizio Palmieri, Barbara Seaworth, Simon Tiberi, and Marina Tadolini
Subjects: MDR/RR-TB, DR-TB treatment guidelines, Shorter regimen, Longer regimens, Infectious and parasitic diseases, RC109-216
Abstract: In December 2022 World Health Organization released a new treatment for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) guideline. The main novelty of this update is two new recommendations (i) a 6-month treatment regimen composed of bedaquiline, pretomanid, linezolid (600 mg), and moxifloxacin (BPaLM) is recommended in place of the 9-month or longer (18-month) regimens in MDR/RR-TB patients, now including extensive pulmonary TB and extrapulmonary TB (except TB involving central nervous system, miliary TB and osteoarticular TB); (ii) the use of the 9-month all-oral regimen rather than longer (18-months) regimen is suggested in patients with MDR/RR-TB and in whom resistance to fluoroquinolones has been excluded. Longer (18-month) treatments remain a valid option in all cases in which shorter regimens cannot be implemented due to intolerance, drug-drug interactions, extensively drug-resistant tuberculosis, extensive forms of extrapulmonary TB, or previous failure. The new guidelines represent a milestone in MDR/RR-TB treatment landscape, setting the basis for a shorter, all-oral, more acceptable, equitable, and patient-centered model for MDR/RR-TB management. However, some challenges remain to be addressed to allow full implementation of the new recommendations.
Published: 2023
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4. Impact of COVID-19 on diagnosis of tuberculosis, multidrug-resistant tuberculosis, and on mortality in 11 countries in Europe, Northern America, and Australia. A Global Tuberculosis Network study

Author: Joanitah Nalunjogi, Sergio Mucching-Toscano, Jean Pierre Sibomana, Rosella Centis, Lia D'Ambrosio, Jan-Willem Alffenaar, Justin Denholm, François-Xavier Blanc, Sergey Borisov, Edvardas Danila, Raquel Duarte, José-María García-García, Delia Goletti, Catherine W.M. Ong, Adrian Rendon, Tania A. Thomas, Simon Tiberi, Martin van den Boom, Giovanni Sotgiu, and Giovanni Battista Migliori
Subjects: COVID-19, Tuberculosis, Drug-resistant TB, TB deaths, Health services, Infectious and parasitic diseases, RC109-216
Abstract: Objectives: Although evidence is growing on the overall impact of the COVID-19 pandemic on tuberculosis (TB) services, global studies based on national data are needed to better quantify the extent of the impact and the countries’ preparedness to tackle the two diseases. The aim of this study was to compare the number of people with new diagnoses or recurrence of TB disease, the number of drug-resistant (DR)-TB, and the number of TB deaths in 2020 vs 2019 in 11 countries in Europe, Northern America, and Australia. Methods: TB managers or directors of national reference centers of the selected countries provided the agreed-upon variables through a validated questionnaire on a monthly basis. A descriptive analysis compared the incidence of TB and DR-TB and mortality of the pre-COVID-19 year (2019) vs the first year of the COVID-19 pandemic (2020). Results: Comparing 2020 vs 2019, lower number of TB cases (new diagnosis or recurrence) was notified in all countries (except USA-Virginia and Australia), and fewer DR-TB notifications (apart from France, Portugal, and Spain). The deaths among TB cases were higher in 2020 compared to 2019 in most countries with three countries (France, The Netherlands, USA-Virginia) reporting minimal TB-related mortality. Conclusions: A comprehensive evaluation of medium-term impact of COVID-19 on TB services would benefit from similar studies in multiple settings and from global availability of treatment outcome data from TB/COVID-19 co-infected patients.
Published: 2023
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5. Delamanid-containing regimens and multidrug-resistant tuberculosis: A systematic review and meta-analysis

Author: Mohammad Javad Nasiri, Moein Zangiabadian, Erfan Arabpour, Sirus Amini, Farima Khalili, Rosella Centis, Lia D'Ambrosio, Justin T. Denholm, H. Simon Schaaf, Martin van den Boom, Xhevat Kurhasani, Margareth Pretti Dalcolmo, Seif Al-Abri, Jeremiah Chakaya, Jan-Willem Alffenaar, Onno Akkerman, Denise Rossato Silva, Marcela Muňoz-Torrico, Barbara Seaworth, Emanuele Pontali, Laura Saderi, Simon Tiberi, Alimuddin Zumla, Giovanni Battista Migliori, and Giovanni Sotgiu
Subjects: TB, MDR-TB, delamanid, bedaquiline, effectiveness, safety, Infectious and parasitic diseases, RC109-216
Abstract: Introduction: Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening condition needing long poly-chemotherapy regimens. As no systematic reviews/meta-analysis is available to comprehensively evaluate the role of delamanid (DLM), we evaluated its effectiveness and safety. Methods: We reviewed the relevant scientific literature published up to January 20, 2022. The pooled success treatment rate with 95% confidence intervals (CI) was assessed using a random-effect model. We assessed studies for quality and bias, and considered P0.05). The overall pooled treatment success rate in DLM and bedaquiline-containing regimens was 75.2% (95% CI 68.1-81.1) with no evidence of publication bias (Begg's test; P >0.05). In experimental studies the pooled treatment success rate of DLM-containing regimens was 72.5 (95% CI 44.2-89.8, P 0.05). Conclusions: In MDR-TB patients receiving DLM, culture conversion and treatment success rates were high despite extensive resistance with limited adverse events.
Published: 2022
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6. World TB Day 2022: Revamping and Reshaping Global TB Control Programs by Advancing Lessons learnt from the COVID-19 pandemic

Author: Eskild Petersen, Seif Al-Abri, Jeremiah Chakaya, Delia Goletti, Liubov Parolina, Christian Wejse, Luchenga Adam Mucheleng'anga, Sulien Al Khalili, Dorothy Yeboah-Manu, Pascalina Chanda-Kapata, Mohammad Javad Nasiri, Patrick S Lungu, Markus Maeurer, Simon Tiberi, Francine Ntoumi, Giovanni Battista-Migliori, and Alimuddin Zumla
Subjects: Infectious and parasitic diseases, RC109-216
Published: 2022
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7. Drug resistant TB – latest developments in epidemiology, diagnostics and management

Author: Simon Tiberi, Natasa Utjesanovic, Jessica Galvin, Rosella Centis, Lia D'Ambrosio, Martin van den Boom, Alimuddin Zumla, and Giovanni Battista Migliori
Subjects: Drug-resistant TB (DR-TB), Treatment Guidelines, BPaL, WHO shorter oral regimen, Adherence, Video Observed Therapy (VOT), Infectious and parasitic diseases, RC109-216
Abstract: Aim: The aim of this review is to inform the reader on the latest developments in epidemiology, diagnostics and management. Epidemiology: Drug-resistant Tuberculosis (DR-TB) continues to be a current global health threat, and is defined by higher morbidity and mortality, sequelae, higher cost and complexity. The WHO classifies drug-resistant TB into 5 categories: isoniazid-resistant TB, rifampicin resistant (RR)-TB and MDR-TB, (TB resistant to isoniazid and rifampicin), pre-extensively drug-resistant TB (pre-XDR-TB) which is MDR-TB with resistance to a fluoroquinolone and finally XDR-TB that is TB resistant to rifampicin, plus any fluoroquinolone, plus at least one further priority A drug (bedaquiline or linezolid). Of 500,000 estimated new cases of RR-TB in 2020, only 157 903 cases are notified. Only about a third of cases are detected and treated annually. Diagnostics: Recently newer rapid diagnostic methods like the GeneXpert, whole genome sequencing and Myc-TB offer solutions for rapid detection of resistance. Treatment: The availability of new TB drugs and shorter treatment regimens have been recommended for the management of DR-TB. Conclusion: Despite advances in diagnostics and treatments we still have to find and treat two thirds of the drug resistant cases that go undetected and therefore go untreated each year. Control of TB and elimination will only occur if cases are detected, diagnosed and treated promptly.
Published: 2022
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8. Armed conflict and human displacement may lead to an increase in the burden of tuberculosis in Europe

Author: Victor Naestholt Dahl, Simon Tiberi, Delia Goletti, and Christian Wejse
Subjects: Tuberculosis, War, Epidemiology, Infectious disease control, Drug resistance, Infectious and parasitic diseases, RC109-216
Published: 2022
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9. Global variations in the burden of SARS-CoV-2 infection and its outcomes in pregnant women by geographical region and country’s income status: a meta-analysis

Author: Gianfranco Spiteri, Olufemi T Oladapo, Nathalie Broutet, Xiu Qiu, Shakila Thangaratinam, Hector Pardo-Hernandez, Heinke Kunst, Vanessa Brizuela, Javier Zamora, Asma Khalil, Simon Tiberi, John Allotey, Elena Stallings, Magnus Yap, Shaunak Chatterjee, Tania Kew, Luke Debenham, Anna Clavé Llavall, Anushka Dixit, Dengyi Zhou, Rishab Balaji, Siang Ing Lee, Mingyang Yuan, Dyuti Coomar, Elena Kostova, Edna Kara, Caron Rahn Kim, Anna Thorson, Lynne Mofenson, Pura Rayco-Solon, Jameela Sheikh, Heidi Lawson, Kehkashan Ansari, Ramón Escuriet, Van T Tong, Kathryn Barry, Wentin Chen, Halimah Khalil, Silvia Fernández-García, Megan Littmoden, Yasmin King, Gurimaan Sandhu, Adeolu Banjoko, Alya Khashaba, Meghnaa Hebbar, Millie Manning, Ankita Gupta, Andrea Gaetano-Gil, Shruti Attarde, Damilola Akande, Dharshini Sambamoorthi, Anoushka Ramkumar, Helen Fraser, Sophie Maddock, Tanisha Rajah, Massa Mamey, Madelon van Wely, Elizabeth van Leeuwen, Sascha Ellington, Julien Beaute, Uma Ram, and Ajith S Nair
Subjects: Medicine (General), R5-920, Infectious and parasitic diseases, RC109-216
Abstract: Introduction The prevalence of COVID-19 and its impact varied between countries and regions. Pregnant women are at high risk of COVID-19 complications compared with non-pregnant women. The magnitude of variations, if any, in SARS-CoV-2 infection rates and its health outcomes among pregnant women by geographical regions and country’s income level is not known.Methods We performed a random-effects meta-analysis as part of the ongoing PregCOV-19 living systematic review (December 2019 to April 2021). We included cohort studies on pregnant women with COVID-19 reporting maternal (mortality, intensive care admission and preterm birth) and offspring (mortality, stillbirth, neonatal intensive care admission) outcomes and grouped them by World Bank geographical region and income level. We reported results as proportions with 95% confidence intervals (CI).Results We included 311 studies (2 003 724 pregnant women, 57 countries). The rates of SARS-CoV-2 infection in pregnant women varied significantly by region (p
Published: 2022
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10. 29 Improving diabetic foot ulcer (DFU) management and outcomes in a North East London Hospital: A Quality Improvement Project (QIP)

Author: Amelia Benjamin, Gadintshware Gaoatswe, and Simon Tiberi
Subjects: Infectious and parasitic diseases, RC109-216
Published: 2022
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11. Clinical management of community-acquired meningitis in adults in the UK and Ireland in 2017: a retrospective cohort study on behalf of the National Infection Trainees Collaborative for Audit and Research (NITCAR)

Author: Amy Robinson, Kamaljit Khalsa, Arjun Chandna, John Bowen, Viva Levee, Jan Coebergh, Tom Solomon, Clive Graham, David Turner, Robert Tilley, Tim Jones, Susan Hopkins, Matthew Stevens, Daniel White, Celestine Eshiwe, Anna Goodman, Ramandeep Singh, Robert S Heyderman, Nicholas Davies, Joseph Thompson, Ed Moran, Sarah Kelly, Martin Williams, Rhea O’Regan, Simon Tiberi, Jonathan Lambourne, Naomi Bulteel, Susan Larkin, Ruth McEwen, Hassan Paraiso, Aarti Shah, Martin Wiselka, Sylviane Defres, Ernest Mutengesa, Maria Krutikov, Ruth Owen, David Griffith, David Harvey, Trupti Patel, Brendan Davies, Emma Mclean, Joanna Allen, Ali Khan, Alastair Miller, Ashutosh Deshpande, Christopher Green, Lewis Jones, Mark Melzer, Fiona McGill, Amanda Fife, Nimal Wickramasinghe, Stephanie Harris, Ewan Hunter, Jayne Ellis, Benedict Rogers, Imogen Fordham, Elen Vink, Victoria Ward, Anna Smith, Andrew Rosser, Alison Muir, Ken Woodhouse, John Shone, Iain Crossingham, Ryan Jayesinghe, Eavan Muldoon, Avneet Shahi, Terry John Evans, Jeremy Wong, Eloisa MacLachlan, Amy Chue, Karishma Gokani, Katherine Ajdukiewicz, Lucinda Barrett, Frances Edwards, Adam Usher, Mairi McLeod, Su su Htwe, Grace Duane, Nicholas Wong, Jennifer Poyner, Jenni Crane, Ollie Lloyd, Emma Chisholm, Ildiko Kustos, Sam Sutton, M. Estee Torok, Isobel Ramsay, Monica Ivan, Joshua York, Jennifer Ansett, Maithili Varadarajan, Priya Sekhon, James Cruise, Shivani Kanabar, Mirella Ling, Charlotte Milne, Jayanta Sarma, Aline Wilson, Lynn Urquhart, Sahar Eldirdiri, Leila White, Jody Aberdein, Phillip Simpson, Hnin Hay Mar, Keying Tan, Eint Shwe Zin thein, Mahmoud Aziz, Anthony Cadwgan, Natasha Weston, Salman Zeb, Angela Houston, Louise Wootton, Iona Willingham, Aimee Johnson, Ashley Horsley, Eamonn Trainor, Olivier Gaillemin, Nicholas J Norton, Katie Cheung, Megan Duxbury, Emilie Bellhouse, Helena Brezovjakova, Kanitkar Tanmay, Alexsander Dawidziuk, Razan Saman, Hugh Adler, Elshadai Ejere, Yiwen Soo, Wendy Beadles, Heather Sturgeon, Brodie Cameron, David Chadwick Ben Tomlinson, Claire McGoldrick, Katie McDowell, Mpho Molosiwa, Katherine FlackAdrian Kennedy, Phoebe Cross, Fay Perry, Vithusha Inpadhas, Sarathy Selvam, Vhairi Bateman, Henry Wu, Monika Pasztor, Ajanthiha Karunakaran, Basma Soliman, Andrew Blanshard, Harish Reddy, Helen Chesterfield, Ben Schroeder, Tee Keat Teoh, Sathyavani Subbarao, Caryn RosmarinLucy Bell, Emma McGuire, Robert Serafino, Ishaan Bhide, Karanjeet Sagoo, Indran Balakrishnan, Kajal Patel, Barzo Faris, Graeme Calver, Ricky Singh, Hazel Sanghvi, Mohamed Eltayeb, and Rathur Haris
Subjects: Medicine
Abstract: Objectives To assess practice in the care of adults with suspected community-acquired bacterial meningitis in the UK and Ireland.Design Retrospective cohort study.Setting 64 UK and Irish hospitals.Participants 1471 adults with community-acquired meningitis of any aetiology in 2017.Results None of the audit standards, from the 2016 UK Joint Specialists Societies guideline on diagnosis and management of meningitis, were met in all cases. With respect to 20 of 30 assessed standards, clinical management provided for patients was in line with recommendations in less than 50% of cases. 45% of patients had blood cultures taken within an hour of admission, 0.5% had a lumbar puncture within 1 hour, 26% within 8 hours. 28% had bacterial molecular diagnostic tests on cerebrospinal fluid. Median time to first dose of antibiotics was 3.2 hours (IQR 1.3–9.2). 80% received empirical parenteral cephalosporins. 55% ≥60 years and 31% of immunocompromised patients received anti-Listeria antibiotics. 21% received steroids. Of the 1471 patients, 20% had confirmed bacterial meningitis. Among those with bacterial meningitis, pneumococcal aetiology, admission to intensive care and initial Glasgow Coma Scale Score less than 14 were associated with in-hospital mortality (adjusted OR (aOR) 2.08, 95% CI 0.96 to 4.48; aOR 4.28, 95% CI 1.81 to 10.1; aOR 2.90, 95% CI 1.26 to 6.71, respectively). Dexamethasone therapy was weakly associated with a reduction in mortality in both those with proven bacterial meningitis (aOR 0.57, 95% CI 0.28 to 1.17) and with pneumococcal meningitis (aOR 0.47, 95% CI 0.20 to 1.10).Conclusion This study demonstrates that clinical care for patients with meningitis in the UK is not in line with current evidence-based national guidelines. Diagnostics and therapeutics should be targeted for quality improvement strategies. Work should be done to improve the impact of guidelines, understand why they are not followed and, once published, ensure they translate into changed practice.
Published: 2022
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12. Worldwide Effects of Coronavirus Disease Pandemic on Tuberculosis Services, January–April 2020

Author: Giovanni Battista Migliori, Pei Min Thong, Onno Akkerman, Jan-Willem Alffenaar, Fernando Álvarez-Navascués, Mourtala Mohamed Assao-Neino, Pascale Valérie Bernard, Joshua Sorba Biala, François-Xavier Blanc, Elena M. Bogorodskaya, Sergey Borisov, Danilo Buonsenso, Marianne Calnan, Paola Francesca Castellotti, Rosella Centis, Jeremiah Muhwa Chakaya, Jin-Gun Cho, Luigi Ruffo Codecasa, Lia D'Ambrosio, Justin Denholm, Martin Enwerem, Maurizio Ferrarese, Tatiana Galvão, Marta García-Clemente, José-María García-García, Gina Gualano, José Antonio Gullón-Blanco, Sandra Inwentarz, Giuseppe Ippolito, Heinke Kunst, Andrei Maryandyshev, Mario Melazzini, Fernanda Carvalho de Queiroz Mello, Marcela Muñoz-Torrico, Patrick Bung Njungfiyini, Domingo Juan Palmero, Fabrizio Palmieri, Pavilio Piccioni, Alberto Piubello, Adrian Rendon, Josefina Sabriá, Matteo Saporiti, Paola Scognamiglio, Samridhi Sharma, Denise Rossato Silva, Mahamadou Bassirou Souleymane, Antonio Spanevello, Eva Tabernero, Marina Tadolini, Michel Eke Tchangou, Alice Boi Yatta Thornton, Simon Tiberi, Zarir F. Udwadia, Giovanni Sotgiu, Catherine Wei Min Ong, and Delia Goletti
Subjects: 2019 novel coronavirus disease, coronavirus disease, COVID-19, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, viruses, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic.
Published: 2020
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13. Using ISARIC 4C mortality score to predict dynamic changes in mortality risk in COVID-19 patients during hospital admission

Author: Tim Crocker-Buque, Jonathan Myles, Adam Brentnall, Rhian Gabe, Stephen Duffy, Sophie Williams, and Simon Tiberi
Subjects: Medicine, Science
Abstract: As SARS-CoV-2 infections continue to cause hospital admissions around the world, there is a continued need to accurately assess those at highest risk of death to guide resource use and clinical management. The ISARIC 4C mortality score provides mortality risk prediction at admission to hospital based on demographic and physiological parameters. Here we evaluate dynamic use of the 4C score at different points following admission. Score components were extracted for 6,373 patients admitted to Barts Health NHS Trust hospitals between 1st August 2020 and 19th July 2021 and total score calculated every 48 hours for 28 days. Area under the receiver operating characteristic (AUC) statistics were used to evaluate discrimination of the score at admission and subsequent inpatient days. Patients who were still in hospital at day 6 were more likely to die if they had a higher score at day 6 than others also still in hospital who had the same score at admission. Discrimination of dynamic scoring in those still in hospital was superior with the area under the curve 0.71 (95% CI 0.69–0.74) at admission and 0.82 (0.80–0.85) by day 8. Clinically useful changes in the dynamic parts of the score are unlikely to be associated with subject-level measurements. Dynamic use of the ISARIC 4C score is likely to provide accurate and timely information on mortality risk during a patient’s hospital admission.
Published: 2022

14. Case studies to illustrate good practice in the management of non-tuberculous mycobacterial pulmonary disease

Author: Simon Tiberi, Marc C. Lipman, and Andres Floto
Subjects: Atypical mycobacteria, Non-tuberculous mycobacteria, Respiratory infection, Imaging, Case studies, Diseases of the respiratory system, RC705-779
Abstract: Pulmonary disease caused by non-tuberculous mycobacteria (NTM-PD) can be a complex condition for health care providers to manage, and delayed diagnosis and treatment failure are common. Here we present three case studies that illustrate key challenges in the diagnosis and treatment of NTM-PD, and provide guidance on these issues. In addition, we make recommendations on how the overall management of NTM-PD may be improved, through strategies such as physician education to recognise NTM-PD, and the development of multidisciplinary teams and patient-support groups.
Published: 2022
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15. A case of Clival Tuberculosis and associated meningitis

Author: William Peter Flynn, Yevedzo Ntuli, Henry Zhang, and Simon Tiberi
Subjects: Mycobacterium tuberculosis, Clivus, Intracranial, Meningitis, Vasculitis, Diseases of the respiratory system, RC705-779, Infectious and parasitic diseases, RC109-216
Abstract: Herein we report a 30-year-old man presenting with fevers, headaches and weight loss. On admission he was disorientated and demonstrated no focal signs of neurological deficit. Magnetic resonance imaging revealed a large area of abnormal bone marrow signal centred within the clivus with extension into the sphenoid sinus and signs of associated basal meningitis. A sphenoid sinus biopsy was performed and proved non diagnostic. The patient was treated empirically with antitubercular therapy (ATT). Lumbar puncture provided cerebrospinal fluid from which Mycobacterium tuberculosis (MTB) was isolated 35 days later. His clinical course was complicated by development of communicating hydrocephalus requiring placement of a ventriculoperitoneal shunt and addition of thalidomide. The patient was discharged following a ten-week admission with complete resolution of symptoms and remains well two years later.
Published: 2021
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16. Global Tuberculosis Report 2020 – Reflections on the Global TB burden, treatment and prevention efforts

Author: Jeremiah Chakaya, Mishal Khan, Francine Ntoumi, Eleni Aklillu, Razia Fatima, Peter Mwaba, Nathan Kapata, Sayoki Mfinanga, Seyed Ehtesham Hasnain, Patrick D.M.C. Katoto, André N.H. Bulabula, Nadia A. Sam-Agudu, Jean B. Nachega, Simon Tiberi, Timothy D. McHugh, Ibrahim Abubakar, and Alimuddin Zumla
Subjects: Tuberculosis, Global TB Report 2020, Treatment, Prevention, Infectious and parasitic diseases, RC109-216
Abstract: The October 2020 Global TB report reviews TB control strategies and United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York. Progress in TB care and prevention has been very slow. In 2019, TB remained the most common cause of death from a single infectious pathogen. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208, 000 deaths among people living with HIV. Adults accounted for 88% and children for 12% of people with TB. The WHO regions of South-East Asia (44%), Africa (25%), and the Western Pacific (18%) had the most people with TB. Eight countries accounted for two thirds of the global total: India (26%), Indonesia (8.5%), China (8.4%), the Philippines (6.0%), Pakistan (5.7%), Nigeria (4.4%), Bangladesh (3.6%) and South Africa (3.6%). Only 30% of the 3.5 million five-year target for children treated for TB was met. Major advances have been development of new all oral regimens for MDRTB and new regimens for preventive therapy. In 2020, the COVID-19 pandemic dislodged TB from the top infectious disease cause of mortality globally. Notably, global TB control efforts were not on track even before the advent of the COVID-19 pandemic. Many challenges remain to improve sub-optimal TB treatment and prevention services. Tuberculosis screening and diagnostic test services need to be ramped up. The major drivers of TB remain undernutrition, poverty, diabetes, tobacco smoking, and household air pollution and these need be addressed to achieve the WHO 2035 TB care and prevention targets. National programs need to include interventions for post-tuberculosis holistic wellbeing. From first detection of COVID-19 global coordination and political will with huge financial investments have led to the development of effective vaccines against SARS-CoV2 infection. The world now needs to similarly focus on development of new vaccines for TB utilizing new technological methods.
Published: 2021
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17. Accelerating development of new shorter TB treatment regimens in anticipation of a resurgence of multi-drug resistant TB due to the COVID-19 pandemic

Author: Simon Tiberi, Michael J. Vjecha, Adam Zumla, Jessica Galvin, Giovanni Battista Migliori, and Alimuddin Zumla
Subjects: Tuberculosis, MDR-TB, New drugs, New treatment regimens, Drug discovery, Pipeline, Infectious and parasitic diseases, RC109-216
Abstract: The WHO 2020 global TB Report estimates that in 2019 there were an estimated 500,000 cases of multi-drug resistant TB (MDR-TB) of which only 186,772 MDR-TB cases were diagnosed, and positive treatment outcomes were achieved in 57% of them. These data highlight the need for accelerating and improving MDR-TB screening, diagnostic, treatment and patient follow-up services. The last decade has seen three new TB drugs being licensed; bedaquiline, delamanid and pretomanid, and combinations these new, existing and repurposed drugs are leading to improved cure rates. The all oral six month WHO regimen for MDR-TB is more tolerable, has higher treatment success rates and lower mortality. However, the unprecedented ongoing COVID-19 pandemic is having major direct and indirect negative impacts on health services overall, including national TB programs and TB services. This adds further to longstanding challenges for tackling MDR-TB such as cost, rollout of diagnostics and drugs, and implementation of latest WHO guidelines for MDR-TB. In light of COVID-19 disruption of TB services, it is anticipated the numbers of MDR-TB cases will rise in 2021 and 2022 and will affect treatment outcomes further. Investing more in development of new TB drugs and shorter MDR-TB treatment regimens is required in anticipation of emerging drug resistance to new TB drug regimens. There is an urgent need for protecting current investments in TB services, sustaining gains being made in TB control and accelerating roll out of TB diagnostic and treatment services.
Published: 2021
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18. World Tuberculosis Day 2021 Theme — ‘The Clock is Ticking’ — and the world is running out of time to deliver the United Nations General Assembly commitments to End TB due to the COVID-19 pandemic

Author: Alimuddin Zumla, Jeremiah Chakaya, Mishal Khan, Razia Fatima, Christian Wejse, Seif Al-Abri, Greg J. Fox, Jean Nachega, Nathan Kapata, Michael Knipper, Miriam Orcutt, Lara Goscé, Ibrahim Abubakar, Tumaini Joseph Nagu, Ferdinand Mugusi, Alice Kizny Gordon, Sivakumar Shanmugam, Nathan Lloyd Bachmann, Connie Lam, Vitali Sintchenko, Frauke Rudolf, Farhana Amanullah, Richard Kock, Najmul Haider, Marc Lipman, Michael King, Markus Maeurer, Delia Goletti, Linda Petrone, Aashifa Yaqoob, Simon Tiberi, Lucica Ditiu, Suvanand Sahu, Ben Marais, Assiya Marat Issayeva, and Eskild Petersen
Subjects: Infectious and parasitic diseases, RC109-216
Published: 2021
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19. Exploring a combined biomarker for tuberculosis treatment response: protocol for a prospective observational cohort study

Author: Marc Lipman, Heinke Kunst, Timothy D McHugh, Simon Tiberi, Mahdad Noursadeghi, Hanif Esmail, Frank Kloprogge, Vanessa Hack, and Julian Surey
Subjects: Medicine
Abstract: Introduction An improved understanding of factors explaining tuberculosis (TB) treatment response is urgently needed to help clinicians optimise and personalise treatment and assist scientists undertaking novel treatment regimen trials. Promising outcome proxy measures, including sputum bacillary load and host immune response, are widely reported with variable results. However, they have not been studied together in combination with antibiotic exposure. The aim of this observational cohort study is to investigate which antibiotic exposures correlate with sputum bacillary load and which with the host immune response. Subsequently, we will explore if these correlations can be used to inform a candidate combined biomarker predicting cure.Methods and analysis All patients aged ≥ 18, diagnosed with drug-sensitive pulmonary TB (culture or molecular test), eligible for standard anti-TB treatment, at selected London, UK TB Services, will be invited to participate in this observational cohort study (target sample size=210). Patients will be asked to give blood for host transcriptomics and antibiotic plasma exposure, in addition to standard of care sputum samples for bacillary load. Antibiotic plasma concentrations will be quantified using a validated liquid chromatograph triple quadrupole mass spectrometer (LC-MS/MS) assay and sputum bacillary load by mycobacterial growth incubator tube time to positivity. Expression from a total of 35 prespecified host blood genes will be quantified using NanoString®. Antibiotic exposure, sputum bacillary load and host blood transcriptomic time series data will be analysed using nonlinear mixed-effects models. Correlations between combinations of longitudinal biomarkers and microbiological cure at the end of treatment and remaining relapse free for 1 year thereafter will be analysed using logistic regression and Cox proportional hazard models.Ethics and dissemination The observational cohort study has been approved by the UK’s HRA REC (20/SW/0007). Written informed consent will be obtained. Results will be disseminated via publication, presentation and through engagement with institutes/companies developing novel anti-TB treatment combinations.
Published: 2021
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20. Surveillance of adverse events in the treatment of drug-resistant tuberculosis: A global feasibility study

Author: Onno Akkerman, Alena Aleksa, Jan-Willem Alffenaar, Nada Hassan Al-Marzouqi, Miguel Arias-Guillén, Evgeny Belilovski, Enrique Bernal, Martin J. Boeree, Sergey E. Borisov, Judith Bruchfeld, Julen Cadiñanos Loidi, Qingshan Cai, Jose A. Caminero, Jose Joaquín Cebrian Gallardo, Rosella Centis, Luigi Ruffo Codecasa, Lia D’Ambrosio, Margareth Dalcolmo, Edvardas Danila, Masoud Dara, Edita Davidavičienė, Lina Davies Forsman, Jorge De Los Rios Jefe, Justin Denholm, Raquel Duarte, Seifeldin Eltaeb Elamin, Maurizio Ferrarese, Alexey Filippov, Shashank Ganatra, Ana Garcia, José-María García-García, Regina Gayoso, Angela Maria Giraldo Montoya, Roscio Gomez Gomez Rosso, Gina Gualano, Wouter Hoefsloot, Biljana Ilievska-Poposka, Jerker Jonsson, Elena Khimova, Liga Kuksa, Heinke Kunst, Rafael Laniado-Laborín, Yang Li, Cecile Magis-Escurra, Vinicio Manfrin, Selene Manga, Valentina Marchese, Elena Martínez Robles, Andrei Maryandyshev, Alberto Matteelli, Giovanni Battista Migliori, Jai B. Mullerpattan, Marcela Munoz-Torrico, Hamdan Mustafa Hamdan, Magnolia Nieto Marcos, Noorliza Mohamad Noordin, Domingo Juan Palmero, Fabrizio Palmieri, Marie-Christine Payen, Alberto Piubello, Emanuele Pontali, Agostina Pontarelli, Sarai Quirós, Adrian Rendon, Alena Skrahina, Agnese Šmite, Ivan Solovic, Giovanni Sotgiu, Mahamadou Bassirou Souleymane, Antonio Spanevello, Maja Stošić, Marina Tadolini, Simon Tiberi, Zarir Farokh Udwadia, Martin van den Boom, Marisa Vescovo, Pietro Viggiani, Dina Visca, Dmitry Zhurkin, and Matteo Zignol
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: The World Health Organization launched a global initiative, known as aDSM (active TB drug safety monitoring and management) to better describe the safety profile of new treatment regimens for drug-resistant tuberculosis (TB) in real-world settings. However, comprehensive surveillance is difficult to implement in several countries.The aim of the aDSM project is to demonstrate the feasibility of implementing national aDSM registers and to describe the type and the frequency of adverse events (AEs) associated with exposure to the new anti-TB drugs.Following a pilot study carried out in 2016, official involvement of TB reference centres/countries into the project was sought and cases treated with bedaquiline- and/or delamanid-containing regimens were consecutively recruited. AEs were prospectively collected ensuring potential attribution of the AE to a specific drug based on its known safety profile.A total of 309 cases were fully reported from 41 centres in 27 countries (65% males; 268 treated with bedaquiline, 20 with delamanid, and 21 with both drugs) out of an estimated 781 cases the participating countries had committed to report by the first quarter of 2019. Keywords: Tuberculosis, MDR-TB, Adverse events, Monitoring, Delamanid, Bedaquiline
Published: 2019
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21. Clinical manifestations, prevalence, risk factors, outcomes, transmission, diagnosis and treatment of COVID-19 in pregnancy and postpartum: a living systematic review protocol

Author: James Thomas, Mercedes Bonet, Caron Kim, Nathalie Broutet, Madelon van Wely, Xiu Qiu, Shakila Thangaratinam, Hector Pardo-Hernandez, Heinke Kunst, Vanessa Brizuela, Javier Zamora, Asma Khalil, Simon Tiberi, John Allotey, Elena Stallings, Magnus Yap, Tania Kew, Luke Debenham, Anushka Dixit, Dengyi Zhou, Rishab Balaji, Siang Ing Lee, Mingyang Yuan, Dyuti Coomar, Elena Kostova, Edna Kara, Anna Thorson, Lynne Mofenson, Shaunak Rhiju Chatterjee, Anna Clavé Llavall, Elisabeth van Leeuwen, Pura Rayco-Solon, and Olufemi Taiwo Oladapo
Subjects: Medicine
Abstract: Introduction Rapid, robust and continually updated evidence synthesis is required to inform management of COVID-19 in pregnant and postpartum women and to keep pace with the emerging evidence during the pandemic.Methods and analysis We plan to undertake a living systematic review to assess the prevalence, clinical manifestations, risk factors, rates of maternal and perinatal complications, potential for mother-to-child transmission, accuracy of diagnostic tests and effectiveness of treatment for COVID-19 in pregnant and postpartum women (including after miscarriage or abortion). We will search Medline, Embase, WHO COVID-19 database, preprint servers, the China National Knowledge Infrastructure system and Wanfang databases from 1 December 2019. We will supplement our search with studies mapped by Cochrane Fertility and Gynaecology group, Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre), COVID-19 study repositories, reference lists and social media blogs. The search will be updated every week and not be restricted by language. We will include observational cohort (≥10 participants) and randomised studies reporting on prevalence of COVID-19 in pregnant and postpartum women, the rates of clinical manifestations and outcomes, risk factors in pregnant and postpartum women alone or in comparison with non-pregnant women with COVID-19 or pregnant women without COVID-19 and studies on tests and treatments for COVID-19. We will additionally include case reports and series with evidence on mother-to-child transmission of SARS-CoV-2 in utero, intrapartum or postpartum. We will appraise the quality of the included studies using appropriate tools to assess the risk of bias. At least two independent reviewers will undertake study selection, quality assessment and data extraction every 2 weeks. We will synthesise the findings using quantitative random effects meta-analysis and report OR or proportions with 95% CIs and prediction intervals. Case reports and series will be reported as qualitative narrative synthesis. Heterogeneity will be reported as I2 and τ2 statistics.Ethics and dissemination Ethical approval is not required as this is a synthesis of primary data. Regular updates of the results will be published on a dedicated website (https://www.birmingham.ac.uk/research/who-collaborating-centre/pregcov/index.aspx) and disseminated through publications, social media and webinars.PROSPERO registration number CRD42020178076.
Published: 2020
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22. The limitations of the Cepheid GeneXpert® Mtb/Rif assay for the diagnosis and management of polyresistant pulmonary tuberculosis

Author: Dahlia Hopmeier, Temi Lampejo, Julian Rycroft, Simon Tiberi, and Mark Melzer
Subjects: Polyresistant TB, Resistance genotyping, Cepheid GeneXpert® Mtb/Rif, Infectious and parasitic diseases, RC109-216
Abstract: Background: Tuberculosis (TB) is the leading world-wide cause of death caused by a single infectious agent. The global treatment success rate for multi-drug resistant (MDR) TB, defined as resistance to at least rifampicin and isoniazid, is estimated at 56%. Mutations in the rpoB gene predict resistance to rifampicin, and are used as a marker of MDR-TB, with standard quadruple therapy recommended in patients testing rpoB wildtype. Case report: A 30-year old woman from Moldova had smear-positive pulmonary TB and was started on standard quadruple therapy after Cepheid GeneXpert® testing detected no mutations in the rpoB gene predictive of rifampicin resistance. After 14 days in hospital, she was considered to be non-infectious despite persistently smear-positive sputum samples and was discharged to continue TB medications in the community. Whole genomic sequencing (WGS) available 8 days after discharge subsequently predicted polyresistant TB (resistance to more than one first-line anti-TB drug apart from rifampicin). Results: The patient was readmitted for treatment modification and required a further 82 days in hospital before sputum samples became culture-negative and respiratory isolation was lifted. Conclusions: This case highlights the limitations of using the absence of mutations in the rpoB gene to predict fully susceptible TB. In cases of polyresistant TB, testing solely for rifampicin resistance may result in inadequate treatment, as resistance to first-line medications apart from rifampicin will not be detected. The lack of guidelines on appropriate de-escalation from respiratory isolation pertaining to pulmonary smear-positive polyresistant TB was also emphasised in this case. Our patient was removed from respiratory isolation when two consecutive sputum samples were culture-negative at 42 days. As sputum samples may remain smear-positive but be culture-negative, this raises the question of whether smear-positivity alone should be used as a measure for de-isolation.
Published: 2020
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23. Post tuberculosis treatment infectious complications

Author: Desmond Hsu, Muhammad Irfan, Kauser Jabeen, Nousheen Iqbal, Rumina Hasan, Giovanni Battista Migliori, Alimuddin Zumla, Dina Visca, Rosella Centis, and Simon Tiberi
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: Following greater attention and follow-up of patients with treated pulmonary tuberculosis (TB), it has emerged that infections are more likely to occur in this cohort of patients. This comes as no surprise, as pulmonary TB is a destructive process that leads to cicatrization, alteration of parenchyma, bronchiectasis, and scarring of the lung, with reduction of lung volumes and an impact on pulmonary function. In addition to relapse and re-infection with TB, other pathogens are increasingly recognized in post-TB patients. This paper serves as a summary and guide on how to approach the post-TB patient with new signs and symptoms of pulmonary infection in order to ensure optimal management and rehabilitation. Keywords: Tuberculosis, Post-treatment complication, Sequelae, Pulmonary rehabilitation, NTM, Bronchiectasis
Published: 2020
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24. Rehabilitation, optimized nutritional care, and boosting host internal milieu to improve long-term treatment outcomes in tuberculosis patients

Author: Onno W. Akkerman, Lies ter Beek, Rosella Centis, Markus Maeurer, Dina Visca, Marcela Muñoz-Torrico, Simon Tiberi, and Giovanni Battista Migliori
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: Background: The holistic management of tuberculosis (TB) patients can improve life expectancy and lost organ function. Rehabilitation: Chronic sequelae are very common among patients who survive TB, which can lead to a further decline in lung function. There is still no guidance for ‘cured’ patients with impaired lung function who need pulmonary rehabilitation. Additional tests for evaluation should be given after the end of treatment, as recent studies have shown the good effect of pulmonary rehabilitation for TB patients. Optimized nutritional care: Malnutrition is very common among TB patients and is related to malabsorption. The latter can cause lower drug exposure, which may result in treatment failure, increasing the risk of death, and can lead to acquired drug resistance. Malnutrition should be assessed according to the Global Leadership Initiative on Malnutrition (GLIM) criteria and the diagnosis should lead to an individualized treatment plan, including sufficient proteins and preferably in combination with adequate training. Protective immune responses: Under normal circumstances, most immune cells use a glucose-based mechanism to generate energy. Therefore the patient’s nutritional status is a key factor in shaping immune responses. Disease-related malnutrition leads to proteolysis and lipolysis. In the end, the identification of individuals who will benefit from immune-modulatory strategies may lead to clinically relevant markers. Keywords: Tuberculosis, Pulmonary rehabilitation, Disease-related malnutrition, Immune response
Published: 2020
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25. Commemorating World TB Day 2020: 'IT’S TIME' — It’s time to End the Global TB Epidemic

Author: Simon Tiberi, Giovanni Battista Migliori, Jeremiah Muhwa Chakaya, Tereza Kaesava, Seif Salem Al Abri, Christian Wejse, Delia Goletti, Nathan Kapata, Giovanni Sotgiu, Jamshed Bomanji, Jean-Pierre Zellweger, Rumina Hasan, Muhammad Irfan, Imran Ahmed, Natalia Pshenichnaya, Irina Vasilieva, Dorothy Yeboah-Manu, Jan-Willem Alffenaar, Hannah Yeijin Kim, Rosella Centis, Daniela Maria Cirillo, Riccardo Alagna, Lia D’Ambrosio, Xiaojing Cui, Bin Cao, Markus Maeurer, Anthony D. Harries, Giuseppe Ippolito, Mario Raviglione, Alimuddin Zumla, and Eskild Petersen
Subjects: Infectious and parasitic diseases, RC109-216
Published: 2020
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26. Precision and personalized medicine and anti-TB treatment: Is TDM feasible for programmatic use?

Author: Jan-Willem C. Alffenaar, Onno W. Akkerman, Hannah Yejin Kim, Simon Tiberi, and Giovanni Battista Migliori
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: Therapeutic Drug Monitoring (TDM) is increasingly recommended to ensure the correct drug dose thereby minimizing adverse events and maximizing regimen efficacy. To facilitate implementation in TB programs, a framework for TDM is urgently needed. TDM is only useful for dose optimization if a patient is on an appropriate regimen guided by drug susceptibility testing. TDM using a targeted approach selecting patients with risk factors for suboptimal drug exposure (e.g. diabetes) or not responding to treatment for drugs with a clear concentration-response relationship may provide the best value for money. Semiquantitative point-of-care tests for detection of low or high drug concentration should be implemented at community level while quantitative assays can be performed at regional or central level. Expanding PK/PD research followed by clinical trials including both clinical outcome as well as cost-effectiveness will increase the level of evidence supporting TDM. Keywords: AR-JP, PINK1, Parkin, Parkinson’s disease, Mitophagy, Ubiquitin, Proteasome, Autophagy
Published: 2020
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27. MDR/XDR-TB management of patients and contacts: Challenges facing the new decade. The 2020 clinical update by the Global Tuberculosis Network

Author: Giovanni Battista Migliori, Simon Tiberi, Alimuddin Zumla, Eskild Petersen, Jeremiah Muhwa Chakaya, Christian Wejse, Marcela Muñoz Torrico, Raquel Duarte, Jan Willem Alffenaar, H. Simon Schaaf, Ben J. Marais, Daniela Maria Cirillo, Riccardo Alagna, Adrian Rendon, Emanuele Pontali, Alberto Piubello, José Figueroa, Gabriella Ferlazzo, Alberto García-Basteiro, Rosella Centis, Dina Visca, Lia D’Ambrosio, Giovanni Sotgiu, T. Abu Arkub, O.W. Akkerman, A. Aleksa, E. Belilovski, E. Bernal, F-X. Blanc, M. Boeree, S. Borisov, J. Bruchfeld, J. Cadiñanos Loidi, J.A. Caminero, A.C. Carvalho, J.J. Cebrian Gallardo, Charalampos, E. Danila, L. Davies Forsman, J. Denholm, K. Dheda, R. Diel, S. Diktanas, C. Dobler, M. Enwerem, S. Esposito, N. Escobar Salinas, A. Filippov, B. Formenti, J.M. García García, D. Goletti, R. Gomez Rosso, G. Gualano, P. Isaakidis, A. Kaluzhenina, S. Koirala, L. Kuksa, H. Kunst, Y. Li, C. Magis-Escurra, V. Manfrin, S. Manga, K. Manika, V. Marchese, E. Martínez Robles, A. Maryandyshev, A. Matteelli, A. Mariani, J. Mazza-Stalder, F. Mello, L. Mendoza, A. Mesi, S. Miliauskas, H. Mustafa Hamdan, N. Ndjeka, M. Nieto Marcos, T.H.M. Ottenhoff, D.J. Palmero, F. Palmieri, A. Papavasileiou, M.C. Payen, A. Pontarelli, M. Pretti Dalcolmo, S. Quirós Fernandez, R. Romero, D. Rossato Silva, A.P. Santos, B. Seaworth, M. Sinitsyn, A. Skrahina, I. Solovic, A. Spanevello, M. Tadolini, C. Torres, Z. Udwadia, M. van den Boom, G.V. Volchenkov, A. Yedilbayev, R. Zaleskis, and J.P. Zellweger
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts.The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines.After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities. Keywords: MDR-TB, XDR-TB, Diagnosis, Treatment, Prevention, Rehabilitation of sequelae
Published: 2020
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28. Tools to implement the World Health Organization End TB Strategy: Addressing common challenges in high and low endemic countries

Author: Seif Al Abri, Thereza Kasaeva, Giovanni Battista Migliori, Delia Goletti, Dominik Zenner, Justin Denholm, Amal Al Maani, Daniela Maria Cirillo, Thomas Schön, Troels Lillebæk, Amina Al-Jardani, Un-Yeong Go, Hannah Monica Dias, Simon Tiberi, Fatma Al Yaquobi, Faryal Ali Khamis, Padmamohan Kurup, Michael Wilson, Ziad Memish, Ali Al Maqbali, Muhammad Akhtar, Christian Wejse, and Eskild Petersen
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: Aim: The purpose of this viewpoint is to summarize the advantages and constraints of the tools and strategies available for reducing the annual incidence of tuberculosis (TB) by implementing the World Health Organization (WHO) End TB Strategy and the linked WHO TB Elimination Framework, with special reference to Oman. Methods: The case-study was built based on the presentations and discussions at an international workshop on TB elimination in low incidence countries organized by the Ministry of Health, Oman, which took place from September 5 to September 7, 2019, and supported by the WHO and European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Results: Existing tools were reviewed, including the screening of migrants for latent TB infection (LTBI) with interferon-gamma release assays, clinical examination for active pulmonary TB (APTB) including chest X-rays, organization of laboratory services, and the existing centres for mandatory health examination of pre-arrival or arriving migrants, including examination for APTB. The need for public–private partnerships to handle the burden of screening arriving migrants for active TB was discussed at length and different models for financing were reviewed. Conclusions: In a country with a high proportion of migrants from high endemic countries, screening for LTBI is of high priority. Molecular typing and the development of public–private partnerships are needed. Keywords: Tuberculosis, Control, Prevention, Latent TB infection, Care, Screening, Migrants
Published: 2020
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29. A postgraduate qualification in tuberculosis—Message in a bottle

Author: Simon Tiberi, Alimuddin Zumla, Mario Raviglione, Marc Lipman, Onn Min Kon, Chris Griffiths, and Giovanni Battista Migliori
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: The TBCert is a distance-learning course, launched in 2019 and hosted by QMUL. The course is open to doctors, nurses, and public health workers who wish to subspecialize in TB. The course was established to elevate TB medicine to a subspecialty. We feel it is imperative to educate health practitioners from different sectors to deliver the most advanced level of care and control activities, standardisze training, reduce clinical variability, and instil best practice. The courses main objectives are to provide a relevant syllabus delivered through high quality teaching from world-class experts using an innovative interactive online platform. The curriculum is based on current internationally accepted (including WHO) guidelines and recommendations. Students are taught with pre-recorded lectures and regular live online webinar discussions delivered by experts in the field. Online discussion groups, one to one teaching-to-one teaching, and mentorship are organiszed to promote a shared as well as a tailored experience that helps students attain the learning outcomes and achieve their expectations. Keywords: Tuberculosis, Postgraduate, Certificate, Education, Training
Published: 2020
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30. Non-tuberculous mycobacterial infections—A neglected and emerging problem

Author: Imran Ahmed, Simon Tiberi, Joveria Farooqi, Kauser Jabeen, Dorothy Yeboah-Manu, Giovanni Battista Migliori, and Rumina Hasan
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: Non-tuberculous mycobacteria (NTM) are ubiquitous dwellers of environmental niches and are an established cause of natural and nosocomial infections. The incidence of NTM infections is rising owing to a growing population of immunocompromised and vulnerable individuals, complex medical and surgical procedures, as well as increased awareness and diagnostic capabilities. The prevalence of different NTM varies between continents, regions, and countries. The true global burden of pulmonary and extrapulmonary disease is unknown and estimates are subject to under and/or over-estimation. Diagnosis requires confirmation by isolation of NTM along with clinical and radiological criteria, which may be suboptimal at all levels. Susceptibility testing is complex and clinical breakpoints are not available for many of the drugs. Frequently, NTM infections are not considered until late in the course of disease. Improved and rapid detection of tuberculosis cases in high-burden countries has, however, also brought NTM infections into the limelight, and has identified a need for research efforts towards rapid diagnostic tests and the identification of biomarkers to monitor the treatment response in patients with NTM infections. Keywords: Non-tuberculous mycobacteria, Diagnosis, Epidemiology, Tuberculosis endemic regions
Published: 2020
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31. Screening for Tuberculosis in Migrants: A Survey by the Global Tuberculosis Network

Author: Lia D’Ambrosio, Rosella Centis, Claudia C. Dobler, Simon Tiberi, Alberto Matteelli, Justin Denholm, Dominik Zenner, Seif Al-Abri, Fatma Alyaquobi, Marcos Abdo Arbex, Evgeny Belilovskiy, François-Xavier Blanc, Sergey Borisov, Anna Cristina C. Carvalho, Jeremiah Muhwa Chakaya, Nicola Cocco, Luigi Ruffo Codecasa, Margareth Pretti Dalcolmo, Keertan Dheda, Anh Tuan Dinh-Xuan, Susanna R. Esposito, José-María García-García, Yang Li, Selene Manga, Valentina Marchese, Marcela Muñoz Torrico, Emanuele Pontali, Adrián Rendon, Denise Rossato Silva, Rupak Singla, Ivan Solovic, Giovanni Sotgiu, Martin van den Boom, Nguyen Viet Nhung, Jean-Pierre Zellweger, and Giovanni Battista Migliori
Subjects: TB, migration, COVID-19, TB infection management, prevention, infection control, Therapeutics. Pharmacology, RM1-950
Abstract: Tuberculosis (TB) does not respect borders, and migration confounds global TB control and elimination. Systematic screening of immigrants from TB high burden settings and—to a lesser degree TB infection (TBI)—is recommended in most countries with a low incidence of TB. The aim of the study was to evaluate the views of a diverse group of international health professionals on TB management among migrants. Participants expressed their level of agreement using a six-point Likert scale with different statements in an online survey available in English, French, Mandarin, Spanish, Portuguese and Russian. The survey consisted of eight sections, covering TB and TBI screening and treatment in migrants. A total of 1055 respondents from 80 countries and territories participated between November 2019 and April 2020. The largest professional groups were pulmonologists (16.8%), other clinicians (30.4%), and nurses (11.8%). Participants generally supported infection control and TB surveillance established practices (administrative interventions, personal protection, etc.), while they disagreed on how to diagnose and manage both TB and TBI, particularly on which TBI regimens to use and when patients should be hospitalised. The results of this first knowledge, attitude and practice study on TB screening and treatment in migrants will inform public health policy and educational resources.
Published: 2021
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32. Bedaquiline and Delamanid Combination Treatment of 5 Patients with Pulmonary Extensively Drug-Resistant Tuberculosis

Author: Andrey Maryandyshev, Emanuele Pontali, Simon Tiberi, Onno Akkerman, Shashank Ganatra, Tsetan Dorji Sadutshang, Jan-Willem Alffenaar, Rohit Amale, Jai Mullerpattan, Sonam Topgyal, Zarir Farokh Udwadia, Rosella Centis, Lia D’Ambrosio, Giovanni Sotgiu, and Giovanni Battista Migliori
Subjects: MDR-TB, XDR-TB, bedaquiline, delamanid, combination treatment, effectiveness, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: We report the experiences of 5 patients taking bedaquiline with delamanid in combination: 1 patient was cured; 3 culture converted, with 2 continuing and 1 changing therapy; and 1 died from respiratory insufficiency. For 2 patients, QT-interval prolongation but no arrhythmias occurred. Use of this therapy is justified for patients with limited options.
Published: 2017
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33. Applicability of the shorter ‘Bangladesh regimen’ in high multidrug-resistant tuberculosis settings

Author: Giovanni Sotgiu, Simon Tiberi, Rosella Centis, Lia D’Ambrosio, Zhenia Fuentes, Alimuddin Zumla, and Giovanni Battista Migliori
Subjects: MDR-TB, XDR-TB, Shorter regimen, Treatment duration, Efficacy, Impact, Infectious and parasitic diseases, RC109-216
Abstract: In spite of the recent introduction of two new drugs (delamanid and bedaquiline) and a few repurposed compounds to treat multidrug-resistant and extensively drug-resistant tuberculosis (MDR- and XDR-TB), clinicians are facing increasing problems in designing effective regimens in severe cases. Recently a 9 to 12-month regimen (known as the ‘Bangladesh regimen’) proved to be effective in treating MDR-TB cases. It included an initial phase of 4 to 6 months of kanamycin, moxifloxacin, prothionamide, clofazimine, pyrazinamide, high-dose isoniazid, and ethambutol, followed by 5 months of moxifloxacin, clofazimine, pyrazinamide, and ethambutol. However, recent evidence from Europe and Latin America identified prevalences of resistance to the first-line drugs in this regimen (ethambutol and pyrazinamide) exceeding 60%, and of prothionamide exceeding 50%. Furthermore, the proportions of resistance to the two most important pillars of the regimen – quinolones and kanamycin – were higher than 40%. Overall, only 14 out of 348 adult patients (4.0%) were susceptible to all of the drugs composing the regimen, and were therefore potentially suitable for the ‘shorter regimen’. A shorter, cheaper, and well-tolerated MDR-TB regimen is likely to impact the number of patients treated and improve adherence if prescribed to the right patients through the systematic use of rapid MTBDRsl testing.
Published: 2017
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34. Classifying new anti-tuberculosis drugs: rationale and future perspectives

Author: Simon Tiberi, Anna Scardigli, Rosella Centis, Lia D’Ambrosio, Marcela Muñoz-Torrico, Miguel Ángel Salazar-Lezama, Antonio Spanevello, Dina Visca, Alimuddin Zumla, Giovanni Battista Migliori, and Jose A. Caminero Luna
Subjects: Anti-TB drugs, MDR/XDR-TB, Fluoroquinolones, Linezolid, Bedaquiline, Delamanid, Infectious and parasitic diseases, RC109-216
Abstract: The classification of anti-tuberculosis (TB) drugs is important as it helps the clinician to build an appropriate anti-TB regimen for multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases that do not fulfil the criteria for the shorter MDR-TB regimen. The World Health Organization (WHO) has recently approved a revision of the classification of new anti-TB drugs based on current evidence on each drug. In the previous WHO guidelines, the choice of drugs was based on efficacy and toxicity in a step-down manner, from group 1 first-line drugs and groups 2–5 second-line drugs, to group 5 drugs with potentially limited efficacy or limited clinical evidence. In the revised WHO classification, exclusively aimed at managing drug-resistant cases, medicines are again listed in hierarchical order from group A to group D. In parallel, a possible future classification is independently proposed. The aim of this viewpoint article is to describe the evolution in WHO TB classification (taking into account an independently proposed new classification) and recent changes in WHO guidance, while commenting on the differences between them. The latest evidence on the ex-group 5 drugs is also discussed.
Published: 2017
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35. Shigellosis and toxic megacolon secondary to Shigella flexneri serotype 3a: The challenges of laboratory diagnosis

Author: Emma McGuire, Simon Tiberi, Holly Ciesielczuk, and Mark Melzer
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: We present a rare case of Shigella flexneri bacteraemia and toxic megacolon, and discuss the challenges of conventional laboratory techniques versus molecular PCR platforms in differentiating between Shigella species and Escherichia coli. Keywords: Shigella flexneri, Shigellosis, Toxic megacolon, Culture, PCR
Published: 2018
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36. Taking forward the Stop TB Partnership and World Health Organization Joint Theme for World TB Day March 24th 2018 — 'Wanted: Leaders for a TB-Free World. You can make history. End TB'

Author: Simon Tiberi, Eskild Petersen, Markus Maeurer, Francine Ntoumi, Dorothy Yeboa-Manu, Peter Mwaba, Cris Vilaplana, Osman Dar, Matthew Bates, Tumena Corrah, Martin Rao, Nathan Kapata, Esam I. Azhar, Ziad A. Memish, Sayoki Mfinanga, Abraham Aseffa, Giuseppe Ippolito, Giovanni Battista Migliori, and Alimuddin Zumla
Subjects: Infectious and parasitic diseases, RC109-216
Published: 2018
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37. Managing severe tuberculosis and its sequelae: from intensive care to surgery and rehabilitation

Author: Simon Tiberi, Marcela Muñoz Torrico, Ananna Rahman, Maria Krutikov, Dina Visca, Denise Rossato Silva, Heinke Kunst, and Giovanni Battista Migliori
Subjects: Tuberculose extensivamente resistente a medicamentos, Tuberculose resistente a múltiplos medicamentos, Cuidados críticos, Abandono do hábito de fumar, Diseases of the respiratory system, RC705-779
Abstract: ABSTRACT Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) continue to challenge physicians and public health specialists. Global treatment outcomes continue to be unsatisfactory, positive outcomes being achieved in only 54% of patients. Overall outcomes are even worse in patients infected with highly resistant strains. Treating MDR-/XDR-TB is difficult because of frequent adverse events, the long duration of drug regimens, the high costs of second-line drugs, chronic post-infectious sequelae, and loss of organ function. Ongoing research efforts (studies and trials) have various aims: increasing the rates of treatment success; understanding the potentialities of new and repurposed drugs; shortening the treatment duration; and reducing the rates of adverse events. It is hoped that better access to rapid diagnostics, increased awareness, and treatments that are more effective will reduce the rate of complications and of lung function impairment. This article aims to discuss the management of severe tuberculosis (defined as that which is potentially life threatening, requiring higher levels of care) and its sequelae, from intensive care to the postoperative period, rehabilitation, and recovery. We also discuss the nonpharmacological interventions available to manage chronic sequelae and improve patient quality of life. Because the majority of MDR-/XDR-TB cases evolve to lung function impairment (typically obstructive but occasionally restrictive), impaired quality of life, and low performance status (as measured by walk tests or other metrics), other interventions (e.g., smoking cessation, pulmonary rehabilitation, vaccination/prevention of secondary bacterial infections/exacerbations, complemented by psychological and nutritional support) are required.
Published: 2019
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38. Management and outcomes of severe childhood tuberculosis in the pediatric intensive care setting: can we identify best practices?

Author: Svetlana Velizarova, Natalia Gabrovska, Albena Spasova, Ben Marais, Elizabeth Page Harausz, Simon Tiberi, Giovanni Battista Migliori, and Davide Manissero
Subjects: Diseases of the respiratory system, RC705-779
Published: 2019
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39. Challenging MDR-TB clinical problems – The case for a new Global TB Consilium supporting the compassionate use of new anti-TB drugs

Author: Simon Tiberi, Emanuele Pontali, Marina Tadolini, Lia D’Ambrosio, and Giovanni Battista Migliori
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: MDR-TB is a growing challenge worldwide, and an obstacle to TB elimination. It is apparent that TB is being replaced by small but growing number of resistant cases with an anticipated 2 million cases of MDR-TB within the next two decades. One of the potential causes of MDR-TB is iatrogenic and we risk losing our new drugs through inexperience and repetition of basic errors of adding single active drugs to failing regimens. Discussion of MDR-TB cases with senior colleagues is not only best practice; it is now embedded in the WHO and many national and local guidelines.TB Consilia act as gatekeepers to the new drugs, monitor guideline adherence and mandate active drug safety monitoring. TB Consilia are also excellent educational tools.TB Consilia are now recommended by funding bodies, the WHO and manufacturers of drugs available for compassionate use in the hope that these drugs will be protected and will continue to be useful in the future. This article briefly discusses Consilia, their origin and evolution and gives some examples of how they operate. Keywords: TB, MDR-TB, TB Consilium, Prevention, New TB drugs, Compassionate use, Alderotti
Published: 2019
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40. Post-Tuberculosis (TB) Treatment: The Role of Surgery and Rehabilitation

Author: Dina Visca, Simon Tiberi, Rosella Centis, Lia D’Ambrosio, Emanuele Pontali, Alessandro Wasum Mariani, Elisabetta Zampogna, Martin van den Boom, Antonio Spanevello, and Giovanni Battista Migliori
Subjects: TB, post-treatment sequelae, surgery, pulmonary rehabilitation, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract: Even though the majority of tuberculosis (TB) programmes consider their work completed when a patient is ‘successfully’ cured, patients often continue to suffer with post-treatment or surgical sequelae. This review focuses on describing the available evidence with regard to the diagnosis and management of post-treatment and surgical sequelae (pulmonary rehabilitation). We carried out a non-systematic literature review based on a PubMed search using specific key-words, including various combinations of ‘TB’, ‘MDR-TB’, ‘XDR-TB’, ‘surgery’, ‘functional evaluation’, ‘sequelae’ and ‘pulmonary rehabilitation’. References of the most important papers were retrieved to improve the search accuracy. We identified the main areas of interest to describe the topic as follows: 1) ‘Surgery’, described through observational studies and reviews, systematic reviews and meta-analyses, IPD (individual data meta-analyses), and official guidelines (GRADE (Grading of Recommendations Assessment, Development and Evaluation) or not GRADE-based); 2) Post-TB treatment functional evaluation; and 3) Pulmonary rehabilitation interventions. We also highlighted the priority areas for research for the three main areas of interest. The collection of high-quality standardized variables would allow advances in the understanding of the need for, and effectiveness of, pulmonary rehabilitation at both the individual and the programmatic level. The initial evidence supports the importance of the adequate functional evaluation of these patients, which is necessary to identify those who will benefit from pulmonary rehabilitation.
Published: 2020
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41. Tuberculosis elimination: where are we now?

Author: Alberto Matteelli, Adrian Rendon, Simon Tiberi, Seif Al-Abri, Constantia Voniatis, Anna Cristina C. Carvalho, Rosella Centis, Lia D'Ambrosio, Dina Visca, Antonio Spanevello, and Giovanni Battista Migliori
Subjects: Diseases of the respiratory system, RC705-779
Abstract: Tuberculosis (TB) still represents a major public health issue in spite of the significant impact of the efforts made by the World Health Organization (WHO) and partners to improve its control. In 2014 WHO launched a new global strategy (End TB) with a vision of a world free of TB, and a 2035 goal of TB elimination (defined as less than one incident case per million). The aim of this article is to summarise the theoretical bases of the End TB Strategy and to analyse progresses and persistent obstacles on the way to TB elimination. The evolution of the WHO recommended strategies of TB control (Directly Observed Therapy, Short Course (DOTS), Stop TB and End TB) are described and the concept of TB elimination is discussed. Furthermore, the eight core activities recently proposed by WHO as the milestones to achieve TB elimination are discussed in detail. Finally, the recently published experiences of Cyprus and Oman on their way towards TB elimination are described, together with the regional experience of Latin America. New prevention, diagnostic and treatment tools are also necessary to increase the speed of the present TB incidence decline.
Published: 2018
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42. Multidrug-Resistant Tuberculosis in Europe, 2010–2011

Author: Gunar Günther, Frank van Leth, Sofia Alexandru, Neus Altet, Korkut Avsar, Didi Bang, Raisa Barbuta, Graham Bothamley, Ana Ciobanu, Valeriu Crudu, Manfred Davilovits, Martin Dedicoat, Raquel Duarte, Gina Gualano, Heinke Kunst, Wiel de Lange, Vaira Leimane, Cecile Magis-Escurra, Anne-Marie McLaughlin, Inge Muylle, Veronika Polcová, Emanuele Pontali, Christina Popa, Rudolf Rumetshofer, Alena Skrahina, Varvara Solodovnikova, Victor Spinu, Simon Tiberi, Piret Viiklepp, and Christoph Lange
Subjects: tuberculosis and other mycobacteria, multidrug-resistant tuberculosis, MDR TB, extensively drug-resistant tuberculosis, XDR TB, drug resistance, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: Drug-resistant Mycobacterium tuberculosis is challenging elimination of tuberculosis (TB). We evaluated risk factors for TB and levels of second-line drug resistance in M. tuberculosis in patients in Europe with multidrug-resistant (MDR) TB. A total of 380 patients with MDR TB and 376 patients with non–MDR TB were enrolled at 23 centers in 16 countries in Europe during 2010–2011. A total of 52.4% of MDR TB patients had never been treated for TB, which suggests primary transmission of MDR M. tuberculosis. At initiation of treatment for MDR TB, 59.7% of M. tuberculosis strains tested were resistant to pyrazinamide, 51.1% were resistant to ≥1 second-line drug, 26.6% were resistant to second-line injectable drugs, 17.6% were resistant to fluoroquinolones, and 6.8% were extensively drug resistant. Previous treatment for TB was the strongest risk factor for MDR TB. High levels of primary transmission and advanced resistance to second-line drugs characterize MDR TB cases in Europe.
Published: 2015
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43. Bedaquiline Phenotypic and Genotypic Susceptibility Testing, Work in Progress!

Author: Simon Tiberi, Andrea Maurizio Cabibbe, Jennifer Tomlins, Daniela Maria Cirillo, and Giovanni Battista Migliori
Subjects: Medicine, Medicine (General), R5-920
Published: 2018
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44. Protecting ourselves from tuberculosis. Describing a historic poster printed in italy on 1937

Author: Francesco Inzirillo, Casimiro Giorgetta, Eugenio Ravalli, Simon Tiberi, Claudio Della Pona, and Mario Robustellini
Subjects: Diseases of the respiratory system, RC705-779
Published: 2014
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45. Combined Use of Delamanid and Bedaquiline to Treat Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: A Systematic Review

Author: Giovanni Battista Migliori, Emanuele Pontali, Giovanni Sotgiu, Rosella Centis, Lia D’Ambrosio, Simon Tiberi, Marina Tadolini, and Susanna Esposito
Subjects: MDR-TB, XDR-TB, delamanid, bedaquiline, effectiveness, safety, tolerability, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: The new drugs delamanid and bedaquiline are increasingly being used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB). The World Health Organization, based on lack of evidence, recommends their use under specific conditions and not in combination. No systematic review has yet evaluated the efficacy, safety, and tolerability of delamanid and bedaquiline used in combination. A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of delamanid and bedaquiline-containing regimens in individuals with pulmonary/extrapulmonary disease, which were bacteriologically confirmed as M/XDR-TB. We used PubMed to identify any relevant manuscripts in English up to the 23 December 2016, excluding editorials and reviews. Three out of 75 manuscripts retrieved satisfied the inclusion criteria, whilst 72 were excluded for dealing with only one drug (three studies), being recommendations (one study) or identifying need for their use (one study), focusing on drug resistance aspects (six studies) or being generic reviews/other studies (61 papers). The studies retrieved reported two XDR-TB cases observed for six months and achieving consistent sputum smear and culture conversion. Case 2 experienced a short break of bedaquiline, which was re-started after introducing verapamil. After a transient and symptom-free increase of the QT interval from week 5 to 17, it then decreased below the 500 ms threshold.
Published: 2017
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46. Carbapenems to Treat Multidrug and Extensively Drug-Resistant Tuberculosis: A Systematic Review

Author: Giovanni Sotgiu, Lia D’Ambrosio, Rosella Centis, Simon Tiberi, Susanna Esposito, Simone Dore, Antonio Spanevello, and Giovanni Battista Migliori
Subjects: MDR-TB, XDR-TB, carbapenems, imipenem, meropenem, ertapenem, effectiveness, safety, tolerability, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Background: Carbapenems (ertapenem, imipenem, meropenem) are used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB), even if the published evidence is limited, particularly when it is otherwise difficult to identify the recommended four active drugs to be included in the regimen. No systematic review to date has ever evaluated the efficacy, safety, and tolerability of carbapenems. Methods: A search of peer-reviewed, scientific evidence was carried out, aimed at evaluating the efficacy/effectiveness, safety, and tolerability of carbapenem-containing regimens in individuals with pulmonary/extra-pulmonary disease which was bacteriologically confirmed as M/XDR-TB. We used PubMed to identify relevant full-text, English manuscripts up to the 20 December 2015, excluding editorials and reviews. Results: Seven out of 160 studies satisfied the inclusion criteria: two on ertapenem, one on imipenem, and four on meropenem, all published between 2005 and 2016. Of seven studies, six were retrospective, four were performed in a single center, two enrolled children, two had a control group, and six reported a proportion of XDR-TB cases higher than 20%. Treatment success was higher than 57% in five studies with culture conversion rates between 60% and 94.8%. Conclusions: The safety and tolerability is very good, with the proportion of adverse events attributable to carbapenems below 15%.
Published: 2016
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47. New and repurposed drugs to treat multidrug- and extensively drug-resistant tuberculosis

Author: Denise Rossato Silva, Margareth Dalcolmo, Simon Tiberi, Marcos Abdo Arbex, Marcela Munoz-Torrico, Raquel Duarte, Lia D’Ambrosio, Dina Visca, Adrian Rendon, Mina Gaga, Alimuddin Zumla, and Giovanni Battista Migliori
Subjects: Tuberculose/terapia, Tuberculose resistente a múltiplos medicamentos, Tuberculose extensivamente resistente a drogas, Antituberculosos, Diseases of the respiratory system, RC705-779
Abstract: ABSTRACT Multidrug-resistant and extensively drug-resistant tuberculosis (MDR-TB and XDR-TB, respectively) continue to represent a challenge for clinicians and public health authorities. Unfortunately, although there have been encouraging reports of higher success rates, the overall rate of favorable outcomes of M/XDR-TB treatment is only 54%, or much lower when the spectrum of drug resistance is beyond that of XDR-TB. Treating M/XDR-TB continues to be a difficult task, because of the high incidence of adverse events, the long duration of treatment, the high cost of the regimens used, and the drain on health care resources. Various trials and studies have recently been undertaken (some already published and others ongoing), all aimed at improving outcomes of M/XDR-TB treatment by changing the overall approach, shortening treatment duration, and developing a universal regimen. The objective of this review was to summarize what has been achieved to date, as far as new and repurposed drugs are concerned, with a special focus on delamanid, bedaquiline, pretomanid, clofazimine, carbapenems, and linezolid. After more than 40 years of neglect, greater attention has recently been paid to the need for new drugs to fight the “white plague”, and promising results are being reported.
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48. Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY)

Author: Obbina Abani, Ali Abbas, Fatima Abbas, Joshua Abbas, Kasim Abbas, Mustafa Abbas, Sadia Abbasi, Hakam Abbass, Alfie Abbott, Alison Abbott, Nabeel Abdallah, Ammar Abdelaziz, Ashraf Abdelaziz, Mohamed Abdelfattah, Bushra Abdelqader, Audrey Abdul, Basir Abdul, Siddiqui Abdul, Althaf Abdul Rasheed, Ajibode Abdulakeem, Rezan Abdul-Kadir, Abdullah Abdullah, Abdulfatahi Abdulmumeen, Rasheed Abdul-Raheem, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer Abeer Ul Amna, Lynn Abel, Katrina Abernethy, Movin Abeywickrema, Chandra Abhinaya, Affyarsyah Abidin, Adebanke Aboaba, Abigail Aboagye-Odei, Christopher Aboah, Heba Aboelela, Hani Abo-Leyah, Karim Abouelela, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Ahmed Abousamra, Mona Abouzaid, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Rebecca Abrams, Hyacinth-John Abu, Ahmed Abu-Arafeh, Syed M Abubacker, Akata Abung, Yousuf Abusamra, Yaa Aceampong, Amaka Achara, Devikumar Acharya, Faustina Acheampong, Prince Acheampong, Sarah Acheampong, Janet Acheson, Shiella Achieng, Andres Acosta, Rebecca Acquah, Catherine Acton, Jacqueline Adabie-Ankrah, Paul Adair, Fiona Adam, Matthew Adam, Huzaifa Adamali, Marta Adamczyk, Carol Adams, Charlotte Adams, Daniel Adams, Kate Adams, Laura Adams, Nikkita Adams, Richard Adams, Tim Adams, Laura Adamu-Ikeme, Krishma Adatia, Kirsty Adcock, Lawrence Addai-Boampong, Afua Addo, Oluwatobi Adeagbo, Ade Adebiyi, Ogunlana Adedeji, Yewande Adegeye, Ken Adegoke, Vicki Adell, Sherna Adenwalla, Femi W Adeoye, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Adedamola Adeyanju, Joyce Adeyemi, Tenifayo Adeyemo, Binay Adhikari, Shanti A Adhikari, Rina Adhikary, Adhikarla Aditya, Patience Adjepong, Gabrielle Adkins, Adnan Adnan, Marguerite Adriaanse, John Aeron-Thomas, Debbie Affleck, Carmel Afnan, Muhammad Afridi, Patricia Afrim, Felicia Akua Afriyie, Zainab A Aftab, Meenakshi Agarwal, Rachel Agbeko, Chris Agbo, Sunil Aggarwal, Arameh Aghababaie, Laura Aguilar Jimenez, Jacqueline Afrakomah Agyekum, Kwame Agyen, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Mohammad Ahmad, Syed Ahmad, Afshan Ahmed, Ashar Ahmed, Asim Ahmed, Basheer A R Ahmed, Bilal Ahmed, Forizuddin Ahmed, Hamze Ahmed, Hanad Ahmed, Irshad Ahmed, Khaled Ahmed, Khalil Ahmed, Liban Ahmed, Mahin Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rawya Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Sana G Ahmed, Syed Ahmed, Syed H Ahmed, Roa Ahmed Ali, Bilal Ahmed Mohamud, Sana Ahmed, Sana Ahmer, Augustine Ahonia, Christine Aiken, Dhiraj Ail, Mark Ainsworth, Myriam Aissa, Lindianne Aitken, Bini Ajay, Abdulakeem Ajibode, Ayesha Ajmi, Nasim Akhtar, Nauman Akhtar, Suha Akili, Bolutito Akinbiyi, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Mohammad Akram, Olugbenro Aktinade, Uzayr Akudi, Ahmad S A R Al Aaraj, Asma Al Balushi, Majd Al Dakhola, Aladdin Al Swaifi, Eslam Al-Abadi, Adegoke Alabi, Narendra Aladangady, Mohamed Alafifi, Ayaz Alam, Sajid Alam, Abbas Al-Asadi, Kyriaki Alatzoglou, Paul Albert, Albertus Albertus, Lorraine Albon, Angela Alcala, Gemma Alcorn, Stephen Alcorn, Aggie Aldana, David Alderdice, Abdullah Aldesouki, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ram Maya Ale, Ana Alegria, Alison Alexander, Courtney Alexander, John Alexander, Peter D G Alexander, Julyan Al-fori, Laith Alghazawi, Osama Alhabsha, Bahij Al-Hakim, Rafil Alhameed, Mohammed Al-Hayali, Shams Al-Hity, Ali Ali, Amanda Ali, Asad Ali, Fawzia R Ali, Jawad Ali, Mariam Ali, Mohamed Ali, Mohammad Ali, Muhammad S Ali, Nayab Ali, Oudai Ali, Ramla Ali, Sakina Ali, Syed Ali, Emilio Aliberti, Jade Alin, Abid Alina, Analyn Alipustain, Bachti Alisjahbana, Fine Aliyuda, Katrin Alizadeh, Maithem Al-Jibury, Saba Al-Juboori, Majid Al-Khalil, Abdullah Alkhudhayri, Moutaz Alkhusheh, Fiona Allan, Nataliya Allan, Alison Allanson, Robert Allcock, Eireann Allen, Jade Allen, Kerry Allen, Louise Allen, Poppy Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Tania Allen, Abiola Alli, Kathryn Allison, Bethan Allman, Helen K Allsop, Lynne Allsop, David Allsup, Amal F T Almahroos, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Riyam Al-Sammarraie, Inji Alshaer, Rustam Al-Shahi Salman, Warkaq Al-Shamkhani, Fadia Alsheikh, Bashar Al-Sheklly, Sara Altaf, Amanda Alty, Mary Alvarez, Maria Alvarez Corral, Edward Alveyn, Maysaa Alzetani, Susan Amamou, Noor Amar, Sakkarai Ambalavanan, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Amel Amelia Ganefianty, Katharine Ames, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Syed Amin, Tara Amin, Badshah Amit, Amjad Amjad, Neelma Amjad, James Amoah-Dankwa, Victoria Amosun, Muhammad Amsal, Khaled Amsha, John Amuasi, Noelia Amutio Martin, Pugh Amy, Ann Anada, Atul Anand, Samantha Anandappa, Satya D Anantapatnaikuni, Ellen Anderson, Julie Anderson, Laura Anderson, Marina Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rebecca Anderson, Rory Anderson, Samantha Anderson, Wendy Anderson, Prematie Andreou, Angela Andrews, Antonette Andrews, Jill Andrews, Joyann Andrews, Kanayochukwu Aneke, Andrew Ang, Wan Wei Ang, Tammy Angel, Aramburo Angela, Paola Angelini, Lazarus Anguvaa, Oleg Anichtchik, Millicent Anim-Somuah, Krishnan Aniruddhan, Jessica Annett, Louise Anning, Maldwyn Ansah, Patrick J Anstey, Rebekah Anstey, Alpha Anthony, Aaron Anthony-Pillai, Philip Antill, Zhelyazkova Antonina, Varghese Anu, Muhammad Anwar, Elena Apetri, Aristeidis Apostolopoulos, Sarah Appleby, Diane Appleyard, Maia F Aquino, Bianca Araba, Samuel Aransiola, Mariana Araujo, Ann Archer, Denise Archer, Samuel Archer, Simon Archer, Daniele Arcoria, Christian Ardley, Ana-Maria Arias, Oluwatoyin Aribike, Ryoki Arimoto, Charlotte Arkley, Charlotte Armah, Ilianna Armata, Jennifer Armistead, Adam Armitage, Ceri Armstrong, Maureen Armstrong, Sonia Armstrong, Wendy Armstrong, Philippa Armtrong, Heike Arndt, Clare Arnison-Newgass, David Arnold, Rachael Arnold, Andrew Arnott, Dhawal Arora, Kavan Arora, Pardeep Arora, Rishi Arora, Arslam Arter, Armena Arumaithurai, Ayush Arya, Rita Arya, Diptesh Aryal, Denisa Asandei, Adeeba Asghar, Malik Asghar, Arif Ashab, Catherine Ashbrook-Raby, Helen Ashby, Jan Ashcroft, John Ashcroft, Samuel Ashcroft, Georgia Asher, Zakariya Ashfak, Ayesha Ashfaq, Abdul Ashish, Dawn Ashley, Sally Ashman-Flavell, Sundar Ashok, Abd-El-Aziz Ashour, Muhammad Z Ashraf, Saima Ashraf, Mohammad B Ashraq, Deborah Ashton, Susan Ashton, Andrew Ashworth, Fiona J Ashworth, Rebecca Ashworth, Arshia Aslam, I Aslam, Suhail Aslam, Laura Aslett, Harshini Asogan, Atif Asrar, Omar Assaf, Raine Astin-Chamberlain, Deborah Athorne, Billie Atkins, Christopher Atkins, Stacey Atkins, John Atkinson, Vicki Atkinson, Abolaji Atomode, Brygitta Atraskiewicz, Abdul A Attia, Eva Attubato, Marie Attwood, Paula Aubrey, Zoltan Auer, Avinash Aujayeb, Aye Chan Thar Aung, Hnin Aung, Hnin Wint Wint Aung, Ko Ko Aung, Kyaw Thu Aung, Nwe Aung, Yin Aung, Zaw Myo Aung, Emily Austin, Karen Austin, Abdusshakur Auwal, Malcolm Avari, Miriam Avery, Nicholas Aveyard, Joanne Avis, Georgina Aviss, Cristina Avram, Paula Avram, Abuzar Awadelkareem, Gabriel Awadzi, Mahmoud Awaly, Atia Awan, Aszad Aya, Eman Ayaz, John Maximilian Ayerh, Amanda Ayers, Jawwad Azam, Ahmed Azeem, Mohammed Azharuddin, Ammar Aziz, Ghazala Aziz, Imran Aziz, N Aziz, Ali Azkoul, Ashaari Azman Shah, Giada Azzopardi, Hocine Azzoug, Fiyinfoluwa Babatunde, Melvin Babi, Babiker Babiker, Gayna Babington, Matthew Babirecki, Marta Babores, Adetona O Babs-Osibodu, Sammy Bacciarelli, Roudi Bachar, Michel-Elie Bachour, Alisjahbana Bachti, Gina Bacon, Jenny Bacon, Bibi Badal, Aysha Badat, Maryuma Bader, Gurpreet R Badhan, Shreya Badhrinarayanan, Joseph P Bae, Alice Baggaley, Amy Baggott, Graham Bagley, Dinesh Bagmane, Lynsey Bagshaw, Kasra Bahadori, Angela Bailey, James Bailey, Katie Bailey, Lindsey Bailey, Liz Bailey, Lucy Bailey, Maria A Bailey, Morgan Bailey, Pippa Bailey, Sarah Bailey, Hamish Baillie, J Kenneth Baillie, Jennifer Bain, Vikram Bains, David Baird, Eilidh Baird, Kevin Baird, Susan Baird, Tracy Baird, Yolanda Baird, Aiysha Bajandouh, Danielle C Baker, Evelyn Baker, Johanne Baker, Josephine Baker, Kenneth Baker, Mark Baker, Rebecca Baker, Terri-Anne Baker, Victoria Baker, Hugh Bakere, Nawar Bakerly, Michelle Baker-Moffatt, Ameet Bakhai, Nauman Bakhtiar, Panos Bakoulas, Dhanalakshmi Bakthavatsalam, Niranjan Balachandran, Andrea Balan, Prasath Balasingam, Theodosios Balaskas, Madhu Balasubramaniam, Nicola Balatoni, Alison Balcombe, Alexander Baldwin, Ashley Baldwin, Caron Baldwin, Danielle Baldwin, Fiona Baldwin, Rebekah Baldwin-Jones, Nichola Bale, James Balfour, Matthew Ball, Robert Ball, K Ballard, Ismael Balluz, Craig Balmforth, Emese Balogh, Abeir Baltmr, Amir Baluwala, Gabby Bambridge, Alasdair Bamford, Amy Bamford, Peter Bamford, Adefunke Bamgboye, Elizabeth Bancroft, Hollie Bancroft, Joyce Banda, Krishna Bandaru, Srini Bandi, Nageswar Bandla, Somaditya Bandyopadhyam, Amit Banerjee, Ritwik Banerjee, Santosh Baniya, Omar Bani-Saad, Harrison Banks, Luke Banks, Paul Banks, Claudia Bann, Helen Bannister, Oliver Bannister, Laura Banton, Tran Bao, Mariamma Baptist, Tanya Baqai, Ananya M Baral, Sharad Chandra Baral, Desislava Baramova, Russel Barber, Emma Barbon, Monica Barbosa, Jamie Barbour, Alexander Barclay, Amanda Barclay, Claire Barclay, George Bardsley, Stephanie Bareford, Shahedal Bari, Morris Barimbing, Amy Barker, Debbie Barker, Erandi Barker, Helen Barker, Joseph Barker, Leon Barker, Lesley Barker, Oliver Barker, Kerry Barker-Williams, Sinha Barkha, Juliana Barla, Gavin Barlow, Richard Barlow, Valerie Barlow, James Barnacle, Alex Barnard, Debi Barnes, Nicky Barnes, Rory Barnes, Theresa Barnes, Calum Barnetson, Amy Barnett, Ashton Barnett-Vanes, Prince Gyenti Barning, William Barnsley, Andrew Barr, David Barr, James Barr, Charlotte Barr, Nina Barratt, Shaney Barratt, Manuella Barrera, Amy Barrett, Fiona Barrett, Jessica Barrett, Sue Barrett, Esther Barrow, Jazz Bartholomew, Claire Bartlett, Georgina Bartlett, James Bartlett, Louise Bartlett, Shauna Bartley, Sandra Bartolmeu-Pires, Anna Barton, Greg Barton, Jill Barton, Lorna Barton, Rachael Barton, Rosaleen Baruah, Sonia Baryschpolec, Hannah Bashir, Archana Bashyal, Betsy Basker, Sudha Basnet, Buddha Basnyat, Ayten Basoglu, Alexander Basran, John Bassett, G Bassett, Chris Bassford, Bengisu Bassoy, Victoria Bastion, Anup Bastola, Anupam Basumatary, Precious Basvi, Jireh A Batac, Vipula R Bataduwaarachchi, Tristan Bate, Harry J Bateman, Kathryn Bateman, Vhairi Bateman, Eleanor Bates, Hayley Bates, Michelle Bates, Simon Bates, Sally Batham, Ana Batista, Amit Batla, Dushyant Batra, Harry Batty, Thomas Batty, Alice Batty, Miranda Baum, Rachel Baumber, Carina Bautista, Fareha Bawa, Tanveer Bawa, Fatima S Bawani, Simon Bax, Matt Baxter, Nicola Baxter, Zachary Baxter, Hannah Bayes, Lee-Ann Bayo, Farid Bazari, Rohit Bazaz, Ahmad Bazli, Laura Beacham, Wendy Beadles, Kirsten Beadon, Philip Beak, Andy Beale, Kathy Beard, Jack Bearpark, Alanna Beasley, Sandee Beattie, Karen Beaumont, Dawn Beaumont-Jewell, Theresa Beaver, Sarah Beavis, Christy Beazley, Sarah Beck, Virginia Beckett, Rosie Beckitt, Sarah Beckley, Heidi Beddall, Seonaid Beddows, Deborah Beeby, Sophia Beeby, Gail Beech, Michelle Beecroft, Nigel Beer, Sally Beer, Jane Beety, Gabriela Bega, Alison Begg, Susan Begg, Sara Beghini, Ayesha Begum, Salman Begum, Selina Begum, Teresa Behan, Roya Behrouzi, Jon Beishon, Claire Beith, James Belcher, Holly Belfield, Katherine Belfield, Ajay Belgaumkar, Dina Bell, Gareth Bell, Gillian Bell, Jessica Bell, Lauren Bell, Louise Bell, Nicholas Bell, Pippa Bell, Stephanie Bell, Jennifer Bellamu, Mary Bellamy, Tammy Bellamy, Arianna Bellini, Amanda Bellis, Fionn Bellis, Lesley Bendall, Naveena Benesh, Nicola Benetti, Leonie Benham, Guy Benison-Horner, Sarah Benkenstein, Tracey Benn, Ann 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Flanagan, Charles Flanders, Nikolaos Flaris, Gail Fleming, Julie Fleming, Lucy Fleming, Paul Fleming, William Flesher, Alison Fletcher, Anna Fletcher, Jonathan Fletcher, Lucy Fletcher, Simon Fletcher, Sophie Fletcher, Fiona Flett, Karen Flewitt, Sarah Flockhart, Christopher Flood, Ian Floodgate, Jonathan Flor, Vincent Florence, Mary Flowerdew, Sharon Floyd, Margaret J Flynn, Rachel Flynn, Claire Foden, Adama Fofana, Georgina Fogarty, Paul Foley, Linda Folkes, Tracey Fong, Daniela M Font, Aiwyne Foo, Jane Foo, Andrew Foot, Helen R Foot, Jayne Foot, Jane Forbes, Amber Ford, Jamie Ford, Imogen Fordham, Jennifer Foreman, Matthew Forester, Mohammad Forkan, Caroline Fornolles, Adam Forrest, Ellie Forsey, Miranda Forsey, Thomas Forshall, Elliot Forster, Abigail Forsyth, Julian Forton, Conrad Foster, Emily Foster, Joseph Foster, Rachel A Foster, Tracy Foster, Angela Foulds, Ian Foulds, Folakemi Fowe, Natasha Fowkes, Emily Fowler, Robert Fowler, Stephen Fowler, Amy Fox, Claire Fox, Heather Fox, 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Giokanini-Royal, Anna Gipson, Barbie Giri, Joanna Girling, Rhian Gisby, Angelena Gkioni, Aikaterini Gkoritsa, Effrossyni Gkrania-Klotsas, Amy Gladwell, James Glanville, Jessica Glasgow, Susannah Glasgow, Jon Glass, Lynn Glass, Sharon Glaysher, Lisa Gledhill, Eleanor Glenday, Ana Glennon, Jodie Glossop, John Glover, Kyle Glover, Michelle Glover, Jan Glover Bengtsson, Deborah Glowski, Sharon Glynn, Chevanthy Gnanalingam, Julie Goddard, Wendy Goddard, Emily Godden, Jo Godden, Sarah Godlee, Emma Godson, Gillian Godwin, Sukanya Gogoi, Aiky Goh, Manjinder Gohel, Rebeca Goiriz, Sriya Gokaraju, Raphael Goldacre, Arthur Goldsmith, Portia Goldsmith, Darren Gomersall, Lucia Gomez, Raquel Gomez-Marcos, Ali Gondal, Celia Gonzalez, Jack Goodall, Vicky Goodall, Bob Goodenough, Anna Goodfellow, Laura Goodfellow, James Goodlife, Camelia Goodwin, Elizabeth Goodwin, Jayne Goodwin, Paula Goodyear, Rajiv Gooentilleke, Michelle Goonasekara, Sheila Gooseman, Shameer Gopal, Chris Gordon, Sally Gordon, Robin 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Hale, Jennie Hale, Carmel Halevy, Paul Halford, William Halford, Alaina Halim, Alistair Hall, Anthony Hall, Claire Hall, Elizabeth Hall, Fiona Hall, Helen Hall, Jennifer Hall, Kathryn Hall, Laura Hall, Jan Hallas, Kyle Hallas, Charles Hallett, Jackie Halliday, Akmal Hallman, Heather Halls, Maryam Hamdollah-Zadeh, Ifedadepo A Hamed-Adekale, Bilal Hameed, Mohammed Hameed, Raph L Hamers, Imran Hamid, Mohamad Hamie, Raymond Hamill, Bethany Hamilton, Fergus Hamilton, Gus Hamilton, Leigh Hamilton, Melanie Hamilton, Nicola Hamilton, Sara Hamilton, Ruth Hamlin, Eleanor Hamlyn, Beatrice Hammans, Shirley Hammersley, Kate Hammerton, Bev Hammond, Emily Hammond, Leah Hammond, Sally Hammond, Fiona Hammonds, Ibrahim Hamoodi, Karen Hampshire, James A Hampson, Jude Hampson, Lucy Hampson, Lisa Hamzah, Jenny Han, Ozan Hanci, Sadiyah Hand, Lala Handayani, Jasmine Handford, Soran Handrean, Nina K Handzewniak, Sarah Haney, Vu Thi Kim Hang, Sheharyar Hanif, E Hanison, Esther Hanison, Jennifer Hannah, Amy 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Ruth Hartley, Tom Hartley, William Hartrey, Phillipa Hartridge, Stuart Hartshorn, Alice Harvey, Angela Harvey, Anna Harvey, Max Harvey, Catherine Harwood, Helen Harwood, Zoe Harzeli, Brigitte Haselden, Kazi Hashem, Mohammed Hashimm, Tadaaki Hashimoto, Imranullah Hashmi, Jack Haslam, Zena Haslam, Grace Hasnip, Adil Hassan, Ali Hassan, Amro Hassan, Awab Hassan, Zeinab Hassan, Sapna Hassasing, Jane Hassell, Philip Hassell, Alex Hastings, Bethany Hastings, Janice Hastings, Sarah Hathaway-Lees, Jonathan Hatton, Jennifer Hau, May Havinden-Williams, Stefan Havlik, Daniel B Hawcutt, Kadean Hawes, Liz Hawes, Nicola Hawes, Lydia Hawker, Annie Hawkins, Joe Hawkins, Nancy Hawkins, W John Hawkins, Dan Hawley, Ed Hawley-Jones, Edward Haworth, Alasdair W Hay, Cathy Hay, Amna Hayat, Jamal Hayat, Mohamed-Riyal Hayathu, Anne Hayes, Jonas Hayes, Kate Hayes, Melony Hayes, Fiona Hayes, Patrick Hayle, Chloe Haylett, Antara Hayman, Melanie Hayman, Matthew Haynes, Richard Haynes, Rachel Hayre, Carole Hays, Sarah Haysom, James Hayward, Patrick Haywood, Hazel Haywood Hasford, Tracy Hazelton, Phoebe Hazenberg, Zhengmai He, Elizabeth Headon, Carrie Heal, Brendan Healy, Jessica L Healy, Amy Hearn, David Heasman, Angela Heath, Debbie Heath, Rowan Heath, Diane Heaton, Adam Heavens, Kerry Hebbron, Catherine Heckman, Gemma Hector, Sadie Heddon, Andy Hedges, Katrine Hedges, Cheryl Heeley, Elaine Heeney, Richard Heinink, Rajdeep Heire, Ingvild Helgesen, Joanne Hemingway, Ulla Hemmila, Beth Hemmings, Scott Hemphill, Deborah Hemsley, Abigail Henderson, Eilidh Henderson, Jennifer Henderson, Steven Henderson, Joanne Henry, Karol Henry, Lavinia Henry, Margo Henry, Natalie Henry, David Henshall, Gillian Herdman, Rosaleen Herdman-Grant, Morag Herkes, Lucas E Hermans, Fe Marie Hernandez, Emma Heron, Lisa Heron, William Herrington, Emilia Heselden, Peta Heslop, Tracey Heslop, Simon Hester, Emily Hetherington, Joseph Hetherington, Chamila Hettiarachchi, Pramodh Hettiarachchi, Hayley Hewer, John Hewertson, Anna Hewetson, Sue Hewins, Nicola Hewitson, Claire Hewitt, Davina Hewitt, Richard Hewitt, Samuel Hey, Robert S Heyderman, Mathis Heydtmann, Joseph Heys, Jonathan Heywood, Meg Hibbert, John Hickey, Naomi Hickey, Peter Hickey, Nicky Hickman, Alex Hicks, Jenny Hicks, Scott R Hicks, Phan Thi Thu Hien, Daniel Higbee, Lucy Higgins, Andrew Higham, Martin Highcock, Judith Highgate, Mondy Hikmat, Amanda Hill, Helen Hill, Joanne Hill, Lisa Hill, Lucy Hill, Phoebe Hill, Uta Hill, Annette Hilldrith, Catherine Hillman-Cooper, Jon Hilton, Zoe Hilton, Sarah Hinch, Andrew Hindle, Esther Hindley, Alice Hindmarsh, Paul Hine, Kim Hinshaw, Clare Hird, Claire Hirst, Lindsay Hirst, Jemma Hives, Htet M Hlaing, Benson Ho, David K K Ho, Rosemary Ho, Michaela Hoare, David Hobden, Gill Hobden, Maria Hobrok, Simon Hobson, Christopher Hodge, Simon Hodge, Lesley Hodgen, George Hodgetts, Holly Hodgkins, Sally Hodgkinson, David Hodgson, Helen Hodgson, Luke Hodgson, Sheila Hodgson, Gemma Hodkinson, Kenneth Hodson, 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Elizabeth Horsley, Sarah Horton, Jane Hosea, Toby Hoskins, Muhammad S Hossain, Rashed Hossain, Maxine Hough, Sarah Hough, Catherine Houghton, Kathryn Houghton, Rebecca Houlihan, Kay Housely, Hamish Houston, Roseanna Hovvels, Lee How, Laura Howaniec, Joanne Howard, Kate Howard, Laura Howard, Linda Howard, Lucy Howard, Megan Howard, Sarah Howard, Stuart Howard, Richard Howard-Griffin, Louise Howard-Sandy, Serena Howe, Alice Howell, Mark Howells, Lyn Howie, Kerry Howlett, Sophie Howlett, Ruth Howman, Josh Hrycaiczuk, Hein Htet, Naing Z Htoon, Su Htwe, Ying Hu, Chiang O H Huah, Sylvia Huang, Kelly Hubbard, Abby Huckle, Shahzya Huda, Alison Hudak, Lisa Hudig, Heather Hudson, Suzanne Hudson, Oli Hudson, Alison Hufton, Connor Huggins, Alistair Hughes, Caitlin Hughes, Emma Hughes, Gareth Hughes, Heather Hughes, Luke Hughes, Martin Hughes, Rachel Hughes, Rebecca Hughes, Samantha Hughes, Stephen Hughes, Vikki Hughes, Wesley Hughes, Lukas Huhn, Ching Hui, Ruth Hulbert, Diana Hull, Grace Hull, Robert Hull, Amanda Hulme, Peter Hulme, Wendy Hulse, George Hulston, Ryan Hum, Megan Hume, Charlotte Humphrey, Alasdair Humphries, Amy Humphries, Joanne Humphries, Charlotte Hunt, Fiona Hunt, Jane Hunt, Jonquil Hunt, Kristen Hunt, Luke Hunt, Molly Hunt, Sophie Hunt, Alexandra Hunter, Catherine Hunter, Ewan Hunter, Karl Hunter, Neil Hunter, Ross Hunter, Sophie Hunter, George Huntington, Fuad Huq, Elizabeth Hurditch, Judith Hurdman, Cian Hurley, Katrina Hurley, Mohammed A Husain, Syeda Y Husaini, Coralie Huson, Afreen Hussain, Chreif Hussain, Ibraar Hussain, Ifza Hussain, Mohammad Hussain, Mohammed Hussain, Muhammad Hussain, Reda Hussain, Rizwana Hussain, Samia Hussain, Sanniah Hussain, Yasmin Hussain, Mohammed Hussam El-Din, Samahir F E M Hussein, Ziad Hussein, Rebecca Hussey, Adiel Haqiq Hussien, Anja Hutchinson, Camille Hutchinson, Dorothy Hutchinson, Elizabeth Hutchinson, John Hutchinson, Claire Hutsby, Paula Hutton, Nguyen Quang Huy, Thuong Huyen, Tran Bang Huyen, Nguyen Thi Huyen Thuong, Hieu Huynh, Daniella Hydes, Jamie Hyde-Wyatt, Niamh Hynes, Megan Hyslop, Angeliki Iakovou, Katherine Ibison, Mazen Ibraheim, Abdalla Ibrahim, Ahmed Ibrahim, Asil Ibrahim, Javed Ibrahim, Mamoun Ibrahim, Mohamed Ibrahim, Wadah Ibrahim, Becky Icke, Adetokunbo Idowu Idowu, Muhammad Idrees, Nauman Idrees, Hina Iftikhar, Mawara Iftikhar, Chukwuemeka Igwe, Ogechukwu Igwe, Mohammad Ijaz, Amaju Ikomi, Clare Iles, Stamatina Iliodromiti, Mary Ilsley, Lorna Ilves, Fatima Mariam Ilyas, La'ali Imam-Gutierrez, Mohamed Iman, Christopher Imray, Haider Imtiaz, Jack Ingham, Jo Ingham, Julie Ingham, Rory Ingham, Tejas Ingle, Jennifer Inglis, Samantha Inglis-Hawkes, Anne Ingram, Luke Ingram, Tanya Ingram, Nicholas Innes, Peter Inns, Vithusha Inpadhas, Ken Inweregbu, Andreea A Ionescu, Ana Ionita, Ilian Petkov Iordanov, Anil Ipe, Javaid Iqbal, Madiha Iqbal, Mishal Iqbal, Mohammed Iqbal, Faisal Iqbal Sait, Iziegbe Irabor, Jane Ireland, Jamie Irisari, Robert Irons, Mohannad Irshad, Muhammad S Irshad, 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Jennings, Jacqui Jennings, Louise Jennings, Virginia Jennings, Ellen Jerome, Douglas Jerry, Greame Jervis, Ellen Jessup-Dunton, Jorge A Jesus Silva, Champa Jetha, Kishan Jethwa, Roshan Kumar Jha, Shaman Jhanji, Khoo Jian, Zhixin Jiao, Laura Jimenez, Ana Jimenez Gil, Jithin Jith, Teishel Joefield, Navraj Johal, Simran Johal, Karine Johannessen, Aisyah Johari, Annie John, Anu John, Maya John, Navin John, Emma Johns, Margaret Johns, Antoinette Johnson, Emma Johnson, Gillian Johnson, Kathryn Johnson, Katie Johnson, Luke Johnson, Mark Johnson, Nelsonseelan Johnson, Oliver Johnson, Rachel Johnson, Brogan Johnston, Claire Johnston, Janet Johnston, Susan Johnston, Victoria Johnston, Dawn Johnstone, Ed Johnstone, Janet Johnstone, Manohar Joishy, Adam Jones, Alistair Jones, Amy Jones, Angela Jones, Annabel Jones, Ben Jones, Bryony Jones, Carys Jones, Ceri Jones, Charlotte Jones, Christine E Jones, Debra Jones, Emily Jones, Gareth Jones, Geraldine Jones, Jac Jones, James Jones, Jonathon Jones, Julie Jones, Kate E Jones, Kimberly Jones, Laura Jones, Laura M Jones, Louise Jones, Mathew Jones, Nancy Jones, Nicola Jones, Olivia Jones, Paul Jones, Philip H Jones, Rhianna Jones, Ruth E Jones, Samantha Jones, Sophie Jones, Stefanie Jones, Steve Jones, Susan Jones, Taya Jones, Thomas Jones, Tim Jones, Tracey Jones, Ramya Jonnalagadda, Rebecca Jordache, Michele Jordan, Sarah Jordan, Abi Jose, Litty Jose, Louise Jose, Sanal Jose, Anna Joseph, Gigee Joseph, P Aiden Joseph, Rosane Joseph, Sibet Joseph, Dhaara Joshi, Mehul Joshi, Pratichi Joshi, Tushar Joshi, Benz Josiah, Lijo Joy, Tiffany Joyce, Hong Ju, Adriel Ju Wen Kwek, Andrew Judd, Edward Jude, Parminder Judge, Jessica Juhl, Sirisha Jujjavarapu, Mark Juniper, Edmund Juszczak, Deepthi Jyothish, Kasamu Kabiru Dawa, Mark Kacar, Nikhil Kadam, Nicole Kader, Ajai Kailey, Matthew Kain, Gail Kakoullis, Azad Kala Bhushan, Richard J K Kalayi, Roobala Kaliannan Periyasami, Efthymia Kallistrou, Thomas Kalmus Eliasz, Seika Kalsoom, Elisa Kam, 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Younes Ibrahim, Eoin Young, Gail Young, Louise Young, Asfand Yousafzar, Sajeda Youssouf, Ahmed Yousuf, Hartantri Yovita, Chrissie Yu, Jack S J Yuan, Nindya Yufaniaputri, Bernard Yung, Daniel Yusef, Said Yusef, Intekhab Yusuf, Anna-Sophia Zafar, Silvia Zagalo, Su Zaher, Aqsa Zahoor, Mahrukh Zainab, Thornton Zak, Kareem Zaki, Nabhan Zakir, Kasia Zalewska, Ane Zamalloa, Mohsin Zaman, Shakir Zaman, Julie Zamikula, Louise Zammit, Marie Zammit-Mangion, Marcelina Zawadzka, Mohammed Zayed, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Darius Zeinali, Jing Zhang, Xiaobei Zhao, Dongling Zheng, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei Thankt Zin, Eva Zincone, Garikai Zindoga, Eleanor Zinkin, Vivian Zinyemba, Christos Zipitis, Letizia Zitter, Arkadiusz Zmierczak, Garazi Zubikarai, Azam Zubir, Naz Zuhra, Rasha Zulaikha, Sabrina Zulfikar, Carol Zullo, Ana Zuriaga-Alvaro, University of St Andrews. Infection and Global Health Division, University of St Andrews. School of Medicine, and Group, RECOVERY Collaborative
Subjects: Adult, Male, Hypoxia/etiology, SARS-CoV-2, COVID-19, 3rd-DAS, General Medicine, Adrenal Cortex Hormones/therapeutic use, AC, Dexamethasone/therapeutic use, Hospitals, Oxygen, Treatment Outcome, SDG 3 - Good Health and Well-being, MCP, Humans, Female
Abstract: Background Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. Methods This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation Findings Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20–2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7–6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2–11·5]). Interpretation In patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation. Funding UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust.
Published: 2023

49. Rapid Diagnosis of XDR and Pre-XDR TB: A Systematic Review of Available Tools

Author: Laura Saderi, Mariangela Puci, Biagio Di Lorenzo, Rosella Centis, Lia D’Ambrosio, Onno W. Akkerman, Jan-Willem C. Alffenaar, José A. Caminero, Jeremiah Muhwa Chakaya, Justin T. Denholm, Xhevat Kurhasani, Catherine W.M. Ong, Adrian Rendon, Denise Rossato Silva, Simon Tiberi, Dominik Zenner, Andrea M. Cabibbe, Giovanni Battista Migliori, and Giovanni Sotgiu
Subjects: Pulmonary and Respiratory Medicine, Genotype, Predictive Value of Tests, Extensively Drug-Resistant Tuberculosis, Tuberculosis, Multidrug-Resistant, Humans, Mycobacterium tuberculosis, Rifampin, Sensitivity and Specificity
Abstract: INTRODUCTION: No previous systematic reviews have comprehensively investigated the features of Xpert MTB/XDR and other rapid tests to diagnose pre-XDR/XDR-TB. The aim of this systematic review is to assess existing rapid diagnostics for pre-XDR/XDR-TB from a point-of-care perspective and describe their technical characteristics (i.e., sensitivity, specificity, positive and negative predictive values). METHODS: Embase, PubMed, Scopus, and Web of Science were searched to detect the articles focused on the accuracy of commercially available rapid molecular diagnostic tests for XDR-TB according to PRISMA guidelines. The analysis compared the diagnostic techniques and approaches in terms of sensitivity, specificity, laboratory complexity, time to confirmed diagnosis. RESULTS: Of 1298 records identified, after valuating article titles and abstracts, 97 (7.5%) records underwent full-text evaluation and 38 records met the inclusion criteria. Two rapid World Health Organization (WHO)-endorsed tests are available: Xpert MTB/XDR and GenoType MTBDRsl (VER1.0 and VER 2.0). Both tests had similar performance, slightly favouring Xpert, although only 2 studies were available (sensitivity 91.4-94; specificity 98.5-99; accuracy 97.2-97.7; PPV 88.9-99.1; NPV 95.8-98.9). CONCLUSIONS: Xpert MTB/XDR could be suggested at near-point-of-care settings to be used primarily as a follow-on test for laboratory-confirmed TB, complementing existing rapid tests detecting at least rifampicin-resistance. Both Xpert MTB/XDR and GenoType MTBDRsl are presently diagnosing what WHO defined, in 2021, as pre-XDR-TB.
Published: 2022

50. Breathing Back Better! A State of the Art on the Benefits of Functional Evaluation and Rehabilitation of Post-Tuberculosis and Post-COVID Lungs

Author: Emanuele, Pontali, Denise Rossato, Silva, Florian M, Marx, Jose Antonio, Caminero, Rosella, Centis, Lia, D'Ambrosio, Jose Maria, Garcia-Garcia, Jeremiah Chakaya, Muhwa, Simon, Tiberi, and Giovanni Battista, Migliori
Subjects: Pulmonary and Respiratory Medicine, Post-Acute COVID-19 Syndrome, Cost-Benefit Analysis, Humans, COVID-19, Tuberculosis, Lung
Abstract: Currently, tuberculosis (TB) and COVID-19 account for substantial morbidity and mortality worldwide, not only during their acute phase, but also because of their sequelae. This scoping review aims to describe the specific aspects of post-TB and post-COVID (long-COVID-19) sequelae, and the implications for post-disease follow-up and rehabilitation. In particular, evidence on how to identify patients affected by sequelae is presented and discussed. A section of the review is dedicated to identifying patients eligible for pulmonary rehabilitation (PR), as not all patients with sequelae are eligible for PR. Components of PR are presented and discussed, as well as their effectiveness. Other essential components to implement comprehensive rehabilitation programmes such as counselling and health education of enrolled patients, evaluation of cost-effectiveness of PR and its impact on health systems as well as research priorities for the future are included in this scoping review.
Published: 2022

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