Prevalence and characterization of integrons in blood culture Enterobacteriaceae and gastrointestinal Escherichia coli in Norway and reporting of a novel class 1 integron-located lincosamide resistance gene

BACKGROUND: Class 1 integrons contain genetic elements for site-specific recombination, capture and mobilization of resistance genes. Studies investigating the prevalence, distribution and types of integron located resistance genes are important for surveillance of antimicrobial resistance and to understand resistance development at the molecular level. METHODS: We determined the prevalence and genetic content of class 1 integrons in Enterobacteriaceae (strain collection 1, n = 192) and E. coli (strain collection 2, n = 53) from bloodstream infections in patients from six Norwegian hospitals by molecular techniques. Class 1 integrons were also characterized in 54 randomly selected multiresistant E. coli isolates from gastrointestinal human infections (strain collection 3). RESULTS: Class 1 integrons were present in 10.9% of the Enterobacteriaceae blood culture isolates of collection 1, all but one (S. Typhi) being E. coli. Data indicated variations in class 1 integron prevalence between hospitals. Class 1 integrons were present in 37% and 34% of the resistant blood culture isolates (collection 1 and 2, respectively) and in 42% of the resistant gastrointestinal E. coli. We detected a total of 10 distinct integron cassette PCR amplicons that varied in size between 0.15 kb and 2.2 kb and contained between zero and three resistance genes. Cassettes encoding resistance to trimethoprim and aminoglycosides were most common. We identified and characterized a novel plasmid-located integron with a cassette-bound novel gene (linF) located downstream of an aadA2 gene cassette. The linF gene encoded a putative 273 aa lincosamide nucleotidyltransferase resistance protein and conferred resistance to lincomycin and clindamycin. The deduced LinF amino acid sequence displayed approximately 35% identity to the Enterococcus faecium and Enterococcus faecalis nucleotidyl transferases encoded by linB and linB' CONCLUSIONS: The present study demonstrated an overall low and stable prevalence of class 1 integron gene cassettes in clinical Enterobacteriaceae and E. coli isolates in Norway. Characterization of the novel lincosamide resistance gene extends the growing list of class 1 integron gene cassettes that confer resistance to an increasing number of antibiotics

Prevalence and Characteristics Associated With Post-COVID-19 Condition Among Nonhospitalized Adolescents and Young Adults

Importance: The prevalence and baseline risk factors of post-COVID-19 condition (PCC) remain unresolved among the large number of young people who experienced mild COVID-19. Objectives: To determine the point prevalence of PCC 6 months after the acute infection, to determine the risk of development of PCC adjusted for possible confounders, and to explore a broad range of potential risk factors. Design, Setting, and Participants: This cohort study included nonhospitalized individuals from 2 counties in Norway between ages 12 and 25 years who underwent reverse transcription-polymerase chain reaction (RT-PCR) testing. At the early convalescent stage and at 6-month follow-up, participants underwent a clinical examination; pulmonary, cardiac, and cognitive functional testing; immunological and organ injury biomarker analyses; and completion of a questionnaire. Participants were classified according to the World Health Organization case definition of PCC at follow-up. Association analyses of 78 potential risk factors were performed. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: The point prevalence of PCC 6 months after RT-PCR testing in the SARS-CoV-2-positive and SARS-CoV-2-negative groups, and the risk difference with corresponding 95% CIs. Results: A total of 404 individuals testing positive for SARS-CoV-2 and 105 individuals testing negative were enrolled (194 male [38.1%]; 102 non-European [20.0%] ethnicity). A total of 22 of the SARS-CoV-2-positive and 4 of the SARS-CoV-2-negative individuals were lost to follow-up, and 16 SARS-CoV-2-negative individuals were excluded due to SARS-CoV-2 infection in the observational period. Hence, 382 SARS-CoV-2-positive participants (mean [SD] age, 18.0 [3.7] years; 152 male [39.8%]) and 85 SARS-CoV-2-negative participants (mean [SD] age, 17.7 [3.2] years; 31 male [36.5%]) could be evaluated. The point prevalence of PCC at 6 months was 48.5% in the SARS-CoV-2-positive group and 47.1% in the control group (risk difference, 1.5%; 95% CI, -10.2% to 13.1%). SARS-CoV-2 positivity was not associated with the development of PCC (relative risk [RR], 1.06; 95% CI, 0.83 to 1.37; final multivariable model utilizing modified Poisson regression). The main risk factor for PCC was symptom severity at baseline (RR, 1.41; 95% CI, 1.27-1.56). Low physical activity (RR, 0.96; 95% CI, 0.92-1.00) and loneliness (RR, 1.01; 95% CI, 1.00-1.02) were also associated, while biological markers were not. Symptom severity correlated with personality traits. Conclusions and Relevance: The persistent symptoms and disability that characterize PCC are associated with factors other than SARS-CoV-2 infection, including psychosocial factors. This finding raises questions about the utility of the World Health Organization case definition and has implications for the planning of health care services as well as for further research on PCC

Hope in action—facing cardiac death: A qualitative study of patients with life-threatening disease

Coping with existential challenges is important when struck by serious disease, but apart from cancer and palliative care little is known about how patients deal with such issues and maintain hope. To explore how patients with life-threatening heart disease experience hope when coping with mortality and other existential challenges, we conducted a qualitative study with semi-structured interviews. We made a purposive sample of 11 participants (26–88 years) who had experienced life-threatening disease: eight participants with serious heart disease, two with cancer, and one with severe chronic obstructive pulmonary disease. Analysis was by systematic text condensation. The findings showed that hope could enhance coping and diminish existential distress when patients were confronted with mortality and other existential challenges. Hope was observed as three types of dynamic work: to shift perception of mortality from overwhelming horror toward suppression or peaceful acceptance, to foster reconciliation instead of uncertainty when adapting to the new phase of life, and to establish go-ahead spirit instead of resignation as their identity. Meaning of life could, hence, be sustained in spite of serious threats to the persons' future, everyday life, and self-conception. The work of hoping could be supported or disturbed by relationships with family, friends, and health care professionals. Hope can be regarded as an active, dynamic state of existential coping among patients with life-threatening disease. Physicians may support this coping and thereby provide personal growth and alleviation of existential distress by skillfully identifying, acknowledging, and participating in the work of hoping performed by the patient

Technology-Enabled Remote Monitoring and Self-Management - Vision for Patient Empowerment Following Cardiac and Vascular Surgery: User Testing and Randomized Controlled Trial Protocol.

BACKGROUND: Tens of thousands of cardiac and vascular surgeries (CaVS) are performed on seniors in Canada and the United Kingdom each year to improve survival, relieve disease symptoms, and improve health-related quality of life (HRQL). However, chronic postsurgical pain (CPSP), undetected or delayed detection of hemodynamic compromise, complications, and related poor functional status are major problems for substantial numbers of patients during the recovery process. To tackle this problem, we aim to refine and test the effectiveness of an eHealth-enabled service delivery intervention, TecHnology-Enabled remote monitoring and Self-MAnagemenT-VIsion for patient EmpoWerment following Cardiac and VasculaR surgery (THE SMArTVIEW, CoVeRed), which combines remote monitoring, education, and self-management training to optimize recovery outcomes and experience of seniors undergoing CaVS in Canada and the United Kingdom. OBJECTIVE: Our objectives are to (1) refine SMArTVIEW via high-fidelity user testing and (2) examine the effectiveness of SMArTVIEW via a randomized controlled trial (RCT). METHODS: CaVS patients and clinicians will engage in two cycles of focus groups and usability testing at each site; feedback will be elicited about expectations and experience of SMArTVIEW, in context. The data will be used to refine the SMArTVIEW eHealth delivery program. Upon transfer to the surgical ward (ie, post-intensive care unit [ICU]), 256 CaVS patients will be reassessed postoperatively and randomly allocated via an interactive Web randomization system to the intervention group or usual care. The SMArTVIEW intervention will run from surgical ward day 2 until 8 weeks following surgery. Outcome assessments will occur on postoperative day 30; at week 8; and at 3, 6, 9, and 12 months. The primary outcome is worst postop pain intensity upon movement in the previous 24 hours (Brief Pain Inventory-Short Form), averaged across the previous 14 days. Secondary outcomes include a composite of postoperative complications related to hemodynamic compromise-death, myocardial infarction, and nonfatal stroke- all-cause mortality and surgical site infections, functional status (Medical Outcomes Study Short Form-12), depressive symptoms (Geriatric Depression Scale), health service utilization-related costs (health service utilization data from the Institute for Clinical Evaluative Sciences data repository), and patient-level cost of recovery (Ambulatory Home Care Record). A linear mixed model will be used to assess the effects of the intervention on the primary outcome, with an a priori contrast of weekly average worst pain intensity upon movement to evaluate the primary endpoint of pain at 8 weeks postoperation. We will also examine the incremental cost of the intervention compared to usual care using a regression model to estimate the difference in expected health care costs between groups. RESULTS: Study start-up is underway and usability testing is scheduled to begin in the fall of 2016. CONCLUSIONS: Given our experience, dedicated industry partners, and related RCT infrastructure, we are confident we can make a lasting contribution to improving the care of seniors who undergo CaVS

Association between diabetes mellitus and active tuberculosis: A systematic review and meta-analysis.

The burgeoning epidemic of diabetes mellitus (DM) is one of the major global health challenges. We systematically reviewed the published literature to provide a summary estimate of the association between DM and active tuberculosis (TB). We searched Medline and EMBASE databases for studies reporting adjusted estimates on the TB-DM association published before December 22, 2015, with no restrictions on region and language. In the meta-analysis, adjusted estimates were pooled using a DerSimonian-Laird random-effects model, according to study design. Risk of bias assessment and sensitivity analyses were conducted. 44 eligible studies were included, which consisted of 58,468,404 subjects from 16 countries. Compared with non-DM patients, DM patients had 3.59-fold (95% confidence interval (CI) 2.25-5.73), 1.55-fold (95% CI 1.39-1.72), and 2.09-fold (95% CI 1.71-2.55) increased risk of active TB in four prospective, 16 retrospective, and 17 case-control studies, respectively. Country income level (3.16-fold in low/middle-vs. 1.73-fold in high-income countries), background TB incidence (2.05-fold in countries with >50 vs. 1.89-fold in countries with ≤50 TB cases per 100,000 person-year), and geographical region (2.44-fold in Asia vs. 1.71-fold in Europe and 1.73-fold in USA/Canada) affected appreciably the estimated association, but potential risk of bias, type of population (general versus clinical), and potential for duplicate data, did not. Microbiological ascertainment for TB (3.03-fold) and/or blood testing for DM (3.10-fold), as well as uncontrolled DM (3.30-fold), resulted in stronger estimated association. DM is associated with a two- to four-fold increased risk of active TB. The association was stronger when ascertainment was based on biological testing rather than medical records or self-report. The burgeoning DM epidemic could impact upon the achievements of the WHO "End TB Strategy" for reducing TB incidence

Listeria monocytogenes infection associated with alemtuzumab – - a case for better preventive strategies

Background The mortality of septicaemia, meningitis and encephalitis caused by Listeria monocytogenes is 20–40%. Twenty-one cases of invasive listeriosis associated with alemtuzumab, including at least 16 in patients with multiple sclerosis, have been published or reported to the World Health Organization Case Safety Reports Database. Three cases were fatal, including at least one patient treated for multiple sclerosis in 2016. Case presentation We report a patient with multiple sclerosis who developed pyrexia, nausea and abdominal discomfort few hours after the third and last infusion of her second alemtuzumab cycle. An infusion related reaction was suspected. The patient had however eaten soft cheese and raw sausage 3 days prior to treatment, and L. monocytogenes septicaemia was diagnosed based on positive blood cultures. Conclusion Listeriosis associated with alemtuzumab is a potentially fatal condition that can mimic an infusion related reaction. As in most other previously reported cases symptoms started rapidly after the last infusion, suggesting that the patient already carried the bacteria prior to the alemtuzumab infusions. The summary of product characteristics recommends patients to avoid foods associated with listeria at least 1 month after treatment. This recommendation should include also the last weeks prior to treatment

Training and assessment of medical specialists in clinical microbiology and infectious diseases in Europe

BACKGROUND There is wide variation in the availability and training of specialists in the diagnosis and management of infections across Europe. OBJECTIVES To describe and reflect on the current objectives, structure and content of European curricula and examinations for the training and assessment of medical specialists in Clinical (Medical) Microbiology (CM/MM) and Infectious Diseases (ID). SOURCES Narrative review of developments over the past two decades and related policy documents and scientific literature. CONTENT Responsibility for curricula and examinations lies with the European Union of Medical Specialists (UEMS). The ID Section of UEMS was inaugurated in 1997 and the MM Section separated from Laboratory Medicine in 2008. The Sections collaborate closely with each other and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Updated European Training Requirements (ETR) were approved for MM in 2017 and ID in 2018. These comprehensive curricula outline the framework for delivery of specialist training and quality control for trainers and training programmes, emphasizing the need for documented, regular formative reviews of progress of trainees. Competencies to be achieved include both specialty-related and generic knowledge, skills and professional behaviours. The indicative length of training is typically 5 years; a year of clinical training is mandated for CM/MM trainees and 6 months of microbiology laboratory training for ID trainees. Each Section is developing examinations using multiple choice questions to test the knowledge base defined in their ETR, to be delivered in 2022 following pilot examinations in 2021. IMPLICATIONS The revised ETRs and European examinations for medical specialists in CM/MM and ID provide benchmarks for national authorities to adapt or adopt locally. Through harmonisation of postgraduate training and assessment, they support the promotion and recognition of high standards of clinical practice and hence improved care for patients throughout Europe, and improved mobility of trainees and specialists