Training in infectious diseases across Europe in 2021 - a survey on training delivery, content and assessment

Objectives: To define the status of infectious diseases (ID) as an approved specialty in Europe; to enumerate the number of specialists (in general and in relation to the overall population) and specialist trainees and describe the content, delivery and evaluation of postgraduate training in ID in different countries.Methods: Structured web-based questionnaire surveys in March 2021 of responsible national authorities, specialist societies and individual country representatives to the Section of Infectious Diseases of the European Union for Medical Specialties. Descriptive analysis of quantitative and qualitative responses.Results: In responses received from 33/35 (94.3%) countries, ID is recognized as a specialty in 24 and as a subspecialty of general internal medicine (GIM) in eight, but it is not recognized in Spain. The number of ID specialists per country varies from <5 per million inhabitants to 78 per million inhabitants. Median length of training is 5 years (interquartile range 4.0–6.0 years) with variable amounts of preceding and/or concurrent GIM. Only 21.2% of countries (7/33) provide the minimum recommended training of 6 months in microbiology and 30% cover competencies such as palliative care, team working and leadership, audit, and quality control. Training is monitored by personal logbook or e-portfolio in 75.8% (25/33) and assessed by final examinations in 69.7% (23/33) of countries, but yearly reviews with trainees only occur in 54.5% (18/33) of countries.Conclusions: There are substantial gaps in modernization of ID training in many countries to match current European training requirements. Joint training with clinical microbiology (CM) and in multidisciplinary team working should be extended. Training/monitoring trainers should find greater focus, together with regular feedback to trainees within many national training programmes.peer-reviewe

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

2015/16 seasonal vaccine effectiveness against hospitalisation with influenza a(H1N1)pdm09 and B among elderly people in Europe: Results from the I-MOVE+ project

We conducted a multicentre test-negative caseâ\u80\u93control study in 27 hospitals of 11 European countries to measure 2015/16 influenza vaccine effectiveness (IVE) against hospitalised influenza A(H1N1)pdm09 and B among people aged â\u89¥ 65 years. Patients swabbed within 7 days after onset of symptoms compatible with severe acute respiratory infection were included. Information on demographics, vaccination and underlying conditions was collected. Using logistic regression, we measured IVE adjusted for potential confounders. We included 355 influenza A(H1N1)pdm09 cases, 110 influenza B cases, and 1,274 controls. Adjusted IVE against influenza A(H1N1)pdm09 was 42% (95% confidence interval (CI): 22 to 57). It was 59% (95% CI: 23 to 78), 48% (95% CI: 5 to 71), 43% (95% CI: 8 to 65) and 39% (95% CI: 7 to 60) in patients with diabetes mellitus, cancer, lung and heart disease, respectively. Adjusted IVE against influenza B was 52% (95% CI: 24 to 70). It was 62% (95% CI: 5 to 85), 60% (95% CI: 18 to 80) and 36% (95% CI: -23 to 67) in patients with diabetes mellitus, lung and heart disease, respectively. 2015/16 IVE estimates against hospitalised influenza in elderly people was moderate against influenza A(H1N1)pdm09 and B, including among those with diabetes mellitus, cancer, lung or heart diseases

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

INFECTIOUS ENDOCARDITIS TO AN INJECTABLE DRUG USER

Background. Injecting drug users are a particular category of patients, where infectious pathology, including infectious endocarditis, is much more common. In Romania, in 2016 there were about 21,000 opioid users (www.ana.gov.ro). Besides opioid drugs, there are also ethnobotanics and a growing trend of injecting amphetamines. Material and methods. We present the case of a young drug user diagnosed in our hospital with infected mitral valve infectious endocarditis. Particularities consist of the type of affected valve and the involvement of a strain of methicillin-sensitive aureus staphylococcus (in a patient with multiple risk factors for infection with multi-resistant strains). Results. Clinical evolution is with many ups and downs because different complications occur, but after 54 days of hospitasization he is out, then valvular surgery takes place and he returns to our clinic for the antibiotic consolidation treatment. Conclusions. This is a case of severe infection in an IDU, with many features indicating a posible negative evolution. Proper antibiotic treatment, associated with other complementary medical interventions, conducted to the favorable uotcome of this young patient

ENDOCARDITA INFECŢIOASĂ LA UN UTILIZATOR DE DROGURI INJECTABILE

Introducere. Utilizatorii de droguri injectabile reprezintă o categorie aparte de pacienţi, la care patologia infecţioasă, inclusiv endocardita infecţioasă, este mult mai frecventă. În România, în 2016 existau aproximativ 21.000 de utilizatori de opiacee (www.ana.gov.ro). În afară de opioide, există şi etnobotanicele şi, de asemenea, o tendinţă în creştere de administrare a amfetaminelor pe cale injectabilă. Material şi metode. Vom prezenta cazul unui tânăr consumator de droguri diagnosticat în clinica noastră cu endocardită infecţioasă de valvă mitrală nativă. Particularităţile constau în tipul de valvă afectată şi implicarea unei tulpini de stafilococ auriu meticilino-sensibil (la un pacient cu multipli factori de risc pentru infecţie cu tulpini multirezistente). Rezultate. Evoluţia clinică este ondulantă, deoarece apar diferite complicaţii, dar, după 54 de zile de spitalizare, este externat, ulterior beneficiază de intervenţie chirurgicală valvulară şi se întoarce în clinica noastră pentru tratament antibiotic de consolidare. Concluzii. Acesta este un caz de infecţie severă la un utilizator de droguri injectabile, cu numeroase caracteristici care indică o potenţială evoluţie nefavorabilă. Tratamentul antibiotic adecvat, asociat cu alte măsuri medicale complementare, a condus la rezultatul favorabil în cazul acestui pacient tânăr

Neurologic Complications of Influenza B Virus Infection in Adults, Romania

We characterized influenza B virus–related neurologic manifestations in an unusually high number of hospitalized adults at a tertiary care facility in Romania during the 2014–15 influenza epidemic season. Of 32 patients with a confirmed laboratory diagnosis of influenza B virus infection, neurologic complications developed in 7 adults (median age 31 years). These complications were clinically diagnosed as confirmed encephalitis (4 patients), possible encephalitis (2 patients), and cerebellar ataxia (1 patient). Two of the patients died. Virus sequencing identified influenza virus B (Yam)-lineage clade 3, which is representative of the B/Phuket/3073/2013 strain, in 4 patients. None of the patients had been vaccinated against influenza. These results suggest that influenza B virus can cause a severe clinical course and should be considered as an etiologic factor for encephalitis

Fatal yellow fever in travelers to Brazil, 2018

Yellow fever virus is a mosquito-borne flavivirus that causes yellow fever, an acute infectious disease that occurs in South America and sub-Saharan Africa. Most patients with yellow fever are asymptomatic, but among the 15% who develop severe illness, the case fatality rate is 20%-60%. Effective live-attenuated virus vaccines are available that protect against yellow fever (1). An outbreak of yellow fever began in Brazil in December 2016; since July 2017, cases in both humans and nonhuman primates have been reported from the states of São Paulo, Minas Gerais, and Rio de Janeiro, including cases occurring near large urban centers in these states (2). On January 16, 2018, the World Health Organization updated yellow fever vaccination recommendations for Brazil to include all persons traveling to or living in Espírito Santo, São Paulo, and Rio de Janeiro states, and certain cities in Bahia state, in addition to areas where vaccination had been recommended before the recent outbreak (3). Since January 2018, 10 travel-related cases of yellow fever, including four deaths, have been reported in international travelers returning from Brazil. None of the 10 travelers had received yellow fever vaccination

Attributable mortality of infections caused by carbapenem-resistant Enterobacterales:results from a prospective, multinational case-control-control matched cohorts study (EURECA)

ObjectivesTo assess the mortality attributable to infections caused by carbapenem-resistant Enterobacterales (CRE) and to investigate the effect of clinical management on differences in observed outcomes in a multinational matched cohort study. MethodsA prospective matched-cohorts study (NCT02709408) was performed in 50 European hospitals from March 2016 to November 2018. The main outcome was 30-day mortality with an active post-discharge follow-up when applied. The CRE cohort included patients with complicated urinary tract infections, complicated intra-abdominal infections, pneumonia, or bacteraemia from other sources because of CRE. Two control cohorts were selected: patients with infection caused by carbapenem-susceptible Enterobacterales (CSE) and patients without infection. Matching criteria included type of infection for the CSE group, hospital ward of CRE detection, and duration of hospital admission up to CRE detection. Multivariable and stratified Cox regression was applied. ResultsThe cohorts included 235 patients with CRE infection, 235 patients with CSE infection, and 705 non-infected patients. The 30-day mortality (95% CI) was 23.8% (18.8-29.6), 10.6% (7.2-15.2), and 8.4% (6.5-10.6), respectively. The difference in 30-day mortality rates between patients with CRE infection when compared with patients with CSE infection was 13.2% (95% CI, 6.3–20.0), (HR, 2.57; 95% CI, 1.55–4.26; p &lt; 0.001), and 15.4% (95% CI, 10.5–20.2) when compared with non-infected patients (HR, 3.85; 95% CI, 2.57–5.77; p &lt; 0.001). The population attributable fraction for 30-day mortality for CRE vs. CSE was 19.28%, and for CRE vs. non-infected patients was 9.61%. After adjustment for baseline variables, the HRs for mortality were 1.87 (95% CI, 0.99–3.50; p 0.06) and 3.65 (95% CI, 2.29–5.82; p &lt; 0.001), respectively. However, when treatment-related time-dependent variables were added, the HR of CRE vs. CSE reduced to 1.44 (95% CI, 0.78–2.67; p 0.24).DiscussionCRE infections are associated with significant attributable mortality and increased adjusted hazard of mortality when compared with CSE infections or patients without infection. Underlying patient characteristics and a delay in appropriate treatment play an important role in the CRE mortality