• Accuracy of the clinical pulmonary infection score to differentiate ventilator-associated tracheobronchitis from ventilator-associated pneumonia.

      Gaudet, Alexandre; Martin-Loeches, Ignacio; Povoa, Pedro; Rodriguez, Alejandro; Salluh, Jorge; Duhamel, Alain; Nseir, Saad (2020-08-03)
      Background: Differentiating Ventilator-Associated Tracheobronchitis (VAT) from Ventilator-Associated Pneumonia (VAP) may be challenging for clinicians, yet their management currently differs. In this study, we evaluated the accuracy of the Clinical Pulmonary Infection Score (CPIS) to differentiate VAT and VAP. Methods: We performed a retrospective analysis based on the data from 2 independent prospective cohorts. Patients of the TAVeM database with a diagnosis of VAT (n = 320) or VAP (n = 369) were included in the derivation cohort. Patients admitted to the Intensive Care Centre of Lille University Hospital between January 1, 2016 and December 31, 2017 who had a diagnosis of VAT (n = 70) or VAP (n = 139) were included in the validation cohort. The accuracy of the CPIS to differentiate VAT from VAP was assessed within the 2 cohorts by calculating sensitivity and specificity values, establishing the ROC curves and choosing the best threshold according to the Youden index. Results: The areas under ROC curves of CPIS to differentiate VAT from VAP were calculated at 0.76 (95% CI [0.72-0.79]) in the derivation cohort and 0.67 (95% CI [0.6-0.75]) in the validation cohort. A CPIS value ≥ 7 was associated with the highest Youden index in both cohorts. With this cut-off, sensitivity and specificity were respectively found at 0.51 and 0.88 in the derivation cohort, and at 0.45 and 0.89 in the validation cohort. Conclusions: A CPIS value ≥ 7 reproducibly allowed to differentiate VAT from VAP with high specificity and PPV and moderate sensitivity and NPV in our derivation and validation cohorts.
    • Social isolation due to the COVID-19 pandemic has led to worse outcomes in females with inflammatory arthritis.

      Maguire, Sinead; O'Shea, Finbar (2020-07-12)
      Background: Prolonged social isolation as a result of the COVID-19 global pandemic has been a source of considerable psychological distress for many people. This can manifest in many ways and if left undetected can impact negatively on general health. It is essential to understand the impact of these conditions on inflammatory arthritis (IA) patients, especially axial spondyloarthropathy (axSpA). Aim: To capture the level of psychological distress for patients with IA following prolonged social isolation. Methods: A survey was sent out to patients with a confirmed diagnosis of IA. This captured changes in sleep, mood, disease activity, employment and general health since the beginning of the social isolation period. A PHQ-4 (Patient Health Questionnaire) was included to determine level of psychological distress. Results: Females with IA reported significantly higher rates of decline in general health (40% vs 16%, p = 0.01), mood disturbance (43.4% vs 26%, p = 0.03) and increased disease activity (50% vs 16%, p = 0.01) compared to males. Evaluating the mean PHQ-4 scores, no significant difference was noted between genders (4.80 vs 3.44, p = 0.10). However, females demonstrated a non-significant trend toward increased rates of moderate to severe psychological distress (40% vs 30%, p = 0.13). Subanalysis of patients with axSpA found high rates of moderate to severe distress in both genders. Conclusions: Females with IA reported significantly higher rates of decline in general health, mood disturbance and increased disease activity during the period of social isolation. This was reflected in a trend towards greater levels of psychological distress.
    • The development and cognitive testing of the positive outcomes HIV PROM: a brief novel patient-reported outcome measure for adults living with HIV.

      Bristowe, K; Murtagh, F E M; Clift, P; James, R; Josh, J; Platt, M; Whetham, J; Nixon, E; Post, F A; McQuillan, K; et al. (2020-07-06)
      Background: People living with HIV experience burdensome multidimensional symptoms and concerns requiring person-centred care. Routine use of patient reported outcome measures can improve outcomes. There is no brief patient reported outcome measure (PROM) that currently reflects the breadth of concerns for people living with HIV. This study aimed to develop and cognitively test a brief novel patient reported outcome measure for use within routine adult HIV care- the "Positive Outcomes" HIV PROM. Methods: Development followed the COSMIN taxonomy and guidance for relevance and comprehensiveness, and Rothrock guidance on development of valid patient reported outcome measures. The Positive Outcomes HIV PROM was developed by a steering group (people living with HIV, HIV professionals and health services researchers) using findings from a previously reported qualitative study of priority outcomes for people living with HIV. The prototype measure was cognitively tested with a purposive sample of people living with HIV. Results: The Positive Outcomes HIV PROM consists of 23 questions (22 structured, and one open question) informed by the priorities of key stakeholders (n = 28 people living with HIV, n = 21 HIV professionals and n = 8 HIV commissioners) to ensure face and content validity, and refined through cognitive testing (n = 6 people living with HIV). Cognitive testing demonstrated high levels of acceptability and accessibility. Conclusions: The Positive Outcomes HIV PROM is the first brief patient reported outcome measure reflecting the diverse needs of people living with HIV designed specifically for use in the clinical setting to support patient assessment and care, and drive service quality improvement. It is derived from primary data on the priority outcomes for people living with HIV and is comprehensive and acceptable. Further psychometric testing is required to ensure reliability and responsiveness.
    • Recommendations for core critical care ultrasound competencies as a part of specialist training in multidisciplinary intensive care: a framework proposed by the European Society of Intensive Care Medicine (ESICM).

      Wong, Adrian; Galarza, Laura; Forni, Lui; De Backer, Daniel; Slama, Michael; Cholley, Bernard; Mayo, Paul; McLean, Anthony; Vieillard-Baron, Antoine; Lichtenstein, Daniel; et al. (2020-07-03)
      Critical care ultrasound (CCUS) is an essential component of intensive care practice. Although existing international guidelines have focused on training principles and determining competency in CCUS, few countries have managed to operationalize this guidance into an accessible, well-structured programme for clinicians training in multidisciplinary intensive care. We seek to update and reaffirm appropriate CCUS scope so that it may be integrated into the international Competency-based Training in Intensive Care Medicine. The resulting recommendations offer the most contemporary and evolved set of core CCUS competencies for an intensive care clinician yet described. Importantly, we discuss the rationale for inclusion but also exclusion of competencies listed. Background/aim: Critical care ultrasound (CCUS) is an essential component of intensive care practice. The purpose of this consensus document is to determine those CCUS competencies that should be a mandatory part of training in multidisciplinary intensive care. Methods: A three-round Delphi method followed by face-to-face meeting among 32 CCUS experts nominated by the European Society of Intensive Care Medicine. Agreement of at least 90% of experts was needed in order to enlist a competency as mandatory. Results: The final list of competencies includes 15 echocardiographic, 5 thoracic, 4 abdominal, deep vein thrombosis diagnosis and central venous access aid. Conclusion: The resulting recommendations offer the most contemporary and evolved set of core CCUS competencies for an intensive care clinician yet described.
    • Update of the treatment of nosocomial pneumonia in the ICU.

      Zaragoza, Rafael; Vidal-Cortés, Pablo; Aguilar, Gerardo; Borges, Marcio; Diaz, Emili; Ferrer, Ricard; Maseda, Emilio; Nieto, Mercedes; Nuvials, Francisco Xavier; Ramirez, Paula; et al. (2020-06-29)
      In accordance with the recommendations of, amongst others, the Surviving Sepsis Campaign and the recently published European treatment guidelines for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), in the event of a patient with such infections, empirical antibiotic treatment must be appropriate and administered as early as possible. The aim of this manuscript is to update treatment protocols by reviewing recently published studies on the treatment of nosocomial pneumonia in the critically ill patients that require invasive respiratory support and patients with HAP from hospital wards that require invasive mechanical ventilation. An interdisciplinary group of experts, comprising specialists in anaesthesia and resuscitation and in intensive care medicine, updated the epidemiology and antimicrobial resistance and established clinical management priorities based on patients' risk factors. Implementation of rapid diagnostic microbiological techniques available and the new antibiotics recently added to the therapeutic arsenal has been reviewed and updated. After analysis of the categories outlined, some recommendations were suggested, and an algorithm to update empirical and targeted treatment in critically ill patients has also been designed. These aspects are key to improve VAP outcomes because of the severity of patients and possible acquisition of multidrug-resistant organisms (MDROs).
    • Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion.

      Verweij, Paul E; Rijnders, Bart J A; Brüggemann, Roger J M; Azoulay, Elie; Bassetti, Matteo; Blot, Stijn; Calandra, Thierry; Clancy, Cornelius J; Cornely, Oliver A; Chiller, Tom; et al. (2020-06-22)
      Purpose: Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies. Methods: A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus. Results: Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus. Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung. Conclusion: A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe Aspergillus disease, and may be of use to study CAPA.
    • Antimicrobial De-Escalation in the ICU: From Recommendations to Level of Evidence.

      Lakbar, Ines; De Waele, Jan J; Tabah, Alexis; Einav, Sharon; Martin-Loeches, Ignacio; Leone, Marc (2020-05-27)
      Antimicrobial de-escalation (ADE) is a component of antimicrobial stewardship (AMS) aimed to reduce exposure to broad-spectrum antimicrobials. In the intensive care unit, ADE is a strong recommendation that is moderately applied in clinical practice. Following a systematic review of the literature, we assessed the studies identified on the topic which included one randomized controlled trial and 20 observational studies. The literature shows a low level of evidence, although observational studies suggested that this procedure is safe. The effects of ADE on the level of resistance of ecological systems and especially on the microbiota are unclear. The reviewers recommend de-escalating antimicrobial treatment in patients requiring long-term antibiotic therapy and considering de-escalation in short-term treatments.
    • Uncomfortably numb: suicide and the psychological undercurrent of COVID-19.

      Hughes, H; Macken, M; Butler, J; Synnott, K (2020-05-21)
    • Sepsis Associated Delirium.

      Atterton, Ben; Paulino, Maria Carolina; Povoa, Pedro; Martin-Loeches, Ignacio (2020-05-18)
      Sepsis is a potentially life-threatening condition caused by a systemic dysregulated host response to infection. The brain is particularly susceptible to the effects of sepsis with clinical manifestations ranging from mild confusion to a deep comatose state. Sepsis-associated delirium(SAD) is a cerebral manifestation commonly occurring in patients with sepsis and is thought to occur due to a combination of neuroinflammation and disturbances in cerebral perfusion, the blood brain barrier (BBB) and neurotransmission. The neurological impairment associated with SAD can persist for months or even longer, after the initial septic episode has subsided which may impair the rehabilitation potential of sepsis survivors. Early identification and treatment of the underlying sepsis is key in the management of SAD as once present it can be difficult to control. Through the regular use of validated screening tools for delirium, cases of SAD can be identified early; this allows potentially aggravating factors to be addressed promptly. The usefulness of biomarkers, neuroimaging and electroencephalopathy (EEG) in the diagnosis of SAD remains controversial. The Society of Critical Care Medicine (SCCM) guidelines advise against the use of medications to treat delirium unless distressing symptoms are present or it is hindering the patient’s ability to wean from organ support.
    • Management of Multi Organ Dysfunction in Neonatal Encephalopathy.

      O'Dea, Mary; Sweetman, Deirdre; Bonifacio, Sonia Lomeli; El-Dib, Mohamed; Austin, Topun; Molloy, Eleanor J (2020-05-15)
      Neonatal Encephalopathy (NE) describes neonates with disturbed neurological function in the first post-natal days of life. NE is an overall term that does not specify the etiology of the encephalopathy although it often involves hypoxia-ischaemia. In NE, although neurological dysfunction is part of the injury and is most predictive of long-term outcome, these infants may also have multiorgan injury and compromise, which further contribute to neurological impairment and long-term morbidities. Therapeutic hypothermia (TH) is the standard of care for moderate to severe NE. Infants with NE may have co-existing immune, respiratory, endocrine, renal, hepatic, and cardiac dysfunction that require individualized management and can be impacted by TH. Non-neurological organ dysfunction not only has a negative effect on long term outcome but may also influence the efficacy of treatments in the acute phase. Post resuscitative care involves stabilization and decisions regarding TH and management of multi-organ dysfunction. This management includes detailed neurological assessment, cardio-respiratory stabilization, glycaemic and fluid control, sepsis evaluation and antibiotics, seizure identification, and monitoring and responding to biochemical and coagulation derangements. The emergence of new biomarkers of specific organ injury may have predictive value and improve the definition of organ injury and prognosis. Further evidence-based research is needed to optimize management of NE, prevent further organ dysfunction and reduce neurodevelopmental impairment.
    • Googling Allergy in Ireland: Content Analysis.

      King, Catherine; Judge, Ciaran; Byrne, Aideen; Conlon, Niall (2020-05-13)
      Background: Internet search engines are increasingly being utilized as the first port of call for medical information by the public. The prevalence of allergies in developed countries has risen steadily over time. There exists significant variability in the quality of health-related information available on the web. Inaccurately diagnosed and mismanaged allergic disease has major downstream effects on patients, general practitioners, and regional allergy services. Objective: This study aimed to verify whether Ireland has a relatively high rate of web-based allergy-related searches, to establish the proportion of medically accurate web pages encountered by the public, and to compare current search results localized to Dublin, Ireland with urban centers elsewhere. Methods: Google Trends was used to evaluate regional interest of allergy-related search terms over a 10-year period using terms "allergy," "allergy test," "food allergy," and "food intolerance." These terms were then inputted into Google search, localizing them to cities in Ireland, the United Kingdom, and the United States. Output for each search was reviewed by two independent clinicians and deemed rational or nonevidence based, as per current best practice guidelines. Searches localized to Dublin were initially completed in 2015 and repeated in 2019 to assess for changes in the quality of search results over time. Results: Ireland has a persistently high demand for web-based information relating to allergy and ranks first worldwide for "allergy test," second for "food allergy" and "food intolerance," and seventh for "allergy" over the specified 10-year timeframe. Results for each of the four subsearches in Dublin (2015) showed that over 60% of websites promoted nonevidence-based diagnostics. A marginal improvement in scientifically robust information was seen in 2019, but results for "allergy test" and "food intolerance" continued to promote alternative testing 57% (8/14) of the time. This strongly contrasted with results localized to Southampton and Rochester, where academic and hospital-affiliated web pages predominantly featured. Government-funded Department of Health websites did not feature in the top five results for Dublin searches "allergy testing," "food allergy," or "food intolerance" in either 2015 or 2019. Conclusions: The Irish public demonstrates a keen interest in seeking allergy-related information on the web. The proportion of evidence-based websites encountered by the Irish public is considerably lower than that encountered by patients in other urban centers. Factors contributing to this are the lack of a specialist register for allergy in Ireland, inadequate funding for allergy centers currently in operation, and insufficient promotion by the health service of their web-based health database, which contains useful patient-oriented information on allergy. Increased funding of clinical allergology services will more meaningfully impact the health of patients if there is a parallel investment by the health service in information and communication technology consultancy to amplify their presence on the web.
    • Recent Progress and Recommendations on Celiac Disease From the Working Group on Prolamin Analysis and Toxicity.

      Scherf, Katharina A; Catassi, Carlo; Chirdo, Fernando; Ciclitira, Paul J; Feighery, Conleth; Gianfrani, Carmen; Koning, Frits; Lundin, Knut E A; Schuppan, Detlef; Smulders, Marinus J M; et al. (2020-03-17)
      Celiac disease (CD) affects a growing number of individuals worldwide. To elucidate the causes for this increase, future multidisciplinary collaboration is key to understanding the interactions between immunoreactive components in gluten-containing cereals and the human gastrointestinal tract and immune system and to devise strategies for CD prevention and treatment beyond the gluten-free diet. During the last meetings, the Working Group on Prolamin Analysis and Toxicity (Prolamin Working Group, PWG) discussed recent progress in the field together with key stakeholders from celiac disease societies, academia, industry and regulatory bodies. Based on the current state of knowledge, this perspective from the PWG members provides recommendations regarding clinical, analytical and legal aspects of CD. The selected key topics that require future multidisciplinary collaborative efforts in the clinical field are to collect robust data on the increasing prevalence of CD, to evaluate what is special about gluten-specific T cells, to study their kinetics and transcriptomics and to put some attention to the identification of the environmental agents that facilitate the breaking of tolerance to gluten. In the field of gluten analysis, the key topics are the precise assessment of gluten immunoreactive components in wheat, rye and barley to understand how these are affected by genetic and environmental factors, the comparison of different methods for compliance monitoring of gluten-free products and the development of improved reference materials for gluten analysis.
    • A proposal for a comprehensive approach to infections across the surgical pathway.

      Sartelli, Massimo; Pagani, Leonardo; Iannazzo, Stefania; Moro, Maria Luisa; Viale, Pierluigi; Pan, Angelo; Ansaloni, Luca; Coccolini, Federico; D'Errico, Marcello Mario; Agreiter, Iris; et al. (2020-02-18)
      Despite evidence supporting the effectiveness of best practices in infection prevention and management, many healthcare workers fail to implement them and evidence-based practices tend to be underused in routine practice. Prevention and management of infections across the surgical pathway should always focus on collaboration among all healthcare workers sharing knowledge of best practices. To clarify key issues in the prevention and management of infections across the surgical pathway, a multidisciplinary task force of experts convened in Ancona, Italy, on May 31, 2019, for a national meeting. This document represents the executive summary of the final statements approved by the expert panel.
    • Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE).

      Yakoub-Agha, Ibrahim; Chabannon, Christian; Bader, Peter; Basak, Grzegorz W; Bonig, Halvard; Ciceri, Fabio; Corbacioglu, Selim; Duarte, Rafael F; Einsele, Hermann; Hudecek, Michael; et al. (2020-01-31)
      Chimeric antigen receptor (CAR) T cells are a novel class of anti-cancer therapy in which autologous or allogeneic T cells are engineered to express a CAR targeting a membrane antigen. In Europe, tisagenlecleucel (Kymriah™) is approved for the treatment of refractory/relapsed acute lymphoblastic leukemia in children and young adults as well as relapsed/refractory diffuse large B-cell lymphoma, while axicabtagene ciloleucel (Yescarta™) is approved for the treatment of relapsed/refractory high-grade B-cell lymphoma and primary mediastinal B-cell lymphoma. Both agents are genetically engineered autologous T cells targeting CD19. These practical recommendations, prepared under the auspices of the European Society of Blood and Marrow Transplantation, relate to patient care and supply chain management under the following headings: patient eligibility, screening laboratory tests and imaging and work-up prior to leukapheresis, how to perform leukapheresis, bridging therapy, lymphodepleting conditioning, product receipt and thawing, infusion of CAR T cells, short-term complications including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, antibiotic prophylaxis, medium-term complications including cytopenias and B-cell aplasia, nursing and psychological support for patients, long-term follow-up, post-authorization safety surveillance, and regulatory issues. These recommendations are not prescriptive and are intended as guidance in the use of this novel therapeutic class.
    • PIM kinase inhibition: co-targeted therapeutic approaches in prostate cancer.

      Luszczak, Sabina; Kumar, Christopher; Sathyadevan, Vignesh Krishna; Simpson, Benjamin S; Gately, Kathy A; Whitaker, Hayley C; Heavey, Susan (2020-01-31)
      PIM kinases have been shown to play a role in prostate cancer development and progression, as well as in some of the hallmarks of cancer, especially proliferation and apoptosis. Their upregulation in prostate cancer has been correlated with decreased patient overall survival and therapy resistance. Initial efforts to inhibit PIM with monotherapies have been hampered by compensatory upregulation of other pathways and drug toxicity, and as such, it has been suggested that co-targeting PIM with other treatment approaches may permit lower doses and be a more viable option in the clinic. Here, we present the rationale and basis for co-targeting PIM with inhibitors of PI3K/mTOR/AKT, JAK/STAT, MYC, stemness, and RNA Polymerase I transcription, along with other therapies, including androgen deprivation, radiotherapy, chemotherapy, and immunotherapy. Such combined approaches could potentially be used as neoadjuvant therapies, limiting the development of resistance to treatments or sensitizing cells to other therapeutics. To determine which drugs should be combined with PIM inhibitors for each patient, it will be key to develop companion diagnostics that predict response to each co-targeted option, hopefully providing a personalized medicine pathway for subsets of prostate cancer patients in the future.
    • Letter to the editor: HIV in women in the World Health Organization (WHO) European Region.

      Aebi-Popp, Karoline; Mulcahy, Fiona; Gilleece, Yvonne; On Behalf Of Wave (2020-01-30)
    • Speech Sound Disorders in Children: An Articulatory Phonology Perspective.

      Namasivayam, Aravind Kumar; Coleman, Deirdre; O'Dwyer, Aisling; van Lieshout, Pascal (2020-01-28)
      Speech Sound Disorders (SSDs) is a generic term used to describe a range of difficulties producing speech sounds in children (McLeod and Baker, 2017). The foundations of clinical assessment, classification and intervention for children with SSD have been heavily influenced by psycholinguistic theory and procedures, which largely posit a firm boundary between phonological processes and phonetics/articulation (Shriberg, 2010). Thus, in many current SSD classification systems the complex relationships between the etiology (distal), processing deficits (proximal) and the behavioral levels (speech symptoms) is under-specified (Terband et al., 2019a). It is critical to understand the complex interactions between these levels as they have implications for differential diagnosis and treatment planning (Terband et al., 2019a). There have been some theoretical attempts made towards understanding these interactions (e.g., McAllister Byun and Tessier, 2016) and characterizing speech patterns in children either solely as the product of speech motor performance limitations or purely as a consequence of phonological/grammatical competence has been challenged (Inkelas and Rose, 2007; McAllister Byun, 2012). In the present paper, we intend to reconcile the phonetic-phonology dichotomy and discuss the interconnectedness between these levels and the nature of SSDs using an alternative perspective based on the notion of an articulatory "gesture" within the broader concepts of the Articulatory Phonology model (AP; Browman and Goldstein, 1992). The articulatory "gesture" serves as a unit of phonological contrast and characterization of the resulting articulatory movements (Browman and Goldstein, 1992; van Lieshout and Goldstein, 2008). We present evidence supporting the notion of articulatory gestures at the level of speech production and as reflected in control processes in the brain and discuss how an articulatory "gesture"-based approach can account for articulatory behaviors in typical and disordered speech production (van Lieshout, 2004; Pouplier and van Lieshout, 2016). Specifically, we discuss how the AP model can provide an explanatory framework for understanding SSDs in children. Although other theories may be able to provide alternate explanations for some of the issues we will discuss, the AP framework in our view generates a unique scope that covers linguistic (phonology) and motor processes in a unified manner.
    • Draft Genome Sequence of an Isolate of Extensively Drug-Resistant Mycobacterium tuberculosis from Nepal.

      Gautam, Sanjay S; Leong, Kelvin W C; Pradhan, Manoj; Singh, Y Ibotomba; Rajbhandari, Sagar K; Ghimire, Gokarna R; Adhikari, Krishna; Shrestha, Uma; Chaudhary, Raina; Ghimire, Gyanendra; et al. (2020-01-23)
      Extensively drug-resistant (XDR) Mycobacterium tuberculosis has become a challenge to the treatment of tuberculosis (TB) in several countries, including Nepal. Here, we report for the first time the draft genome sequence of an isolate of XDR-TB collected in Nepal and describe single-nucleotide variations associated with its extensively drug-resistant phenotype.
    • Impact of Chronic Obstructive Pulmonary Disease on Incidence, Microbiology and Outcome of Ventilator-Associated Lower Respiratory Tract Infections.

      Rouzé, Anahita; Boddaert, Pauline; Martin-Loeches, Ignacio; Povoa, Pedro; Rodriguez, Alejandro; Ramdane, Nassima; Salluh, Jorge; Houard, Marion; Nseir, Saad (2020-01-23)
      Objectives: To determine the impact of chronic obstructive pulmonary disease (COPD) on incidence, microbiology, and outcomes of ventilator-associated lower respiratory tract infections (VA-LRTI). Methods: Planned ancillary analysis of TAVeM study, including 2960 consecutive adult patients who received invasive mechanical ventilation (MV) > 48 h. COPD patients (n = 494) were compared to non-COPD patients (n = 2466). The diagnosis of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) was based on clinical, radiological and quantitative microbiological criteria. Results: No significant difference was found in VAP (12% versus 13%, p = 0.931), or VAT incidence (13% versus 10%, p = 0.093) between COPD and non-COPD patients. Among patients with VA-LRTI, Escherichia coli and Stenotrophomonas maltophilia were significantly more frequent in COPD patients as compared with non-COPD patients. However, COPD had no significant impact on multidrug-resistant bacteria incidence. Appropriate antibiotic treatment was not significantly associated with progression from VAT to VAP among COPD patients who developed VAT, unlike non-COPD patients. Among COPD patients, patients who developed VAT or VAP had significantly longer MV duration (17 days (9-30) or 15 (8-27) versus 7 (4-12), p < 0.001) and intensive care unit (ICU) length of stay (24 (17-39) or 21 (14-40) versus 12 (8-19), p < 0.001) than patients without VA-LRTI. ICU mortality was also higher in COPD patients who developed VAP (44%), but not VAT(38%), as compared to no VA-LRTI (26%, p = 0.006). These worse outcomes associated with VA-LRTI were similar among non-COPD patients. Conclusions: COPD had no significant impact on incidence or outcomes of patients who developed VAP or VAT.