Early plasma interferon-β levels as a predictive marker of COVID-19 severe clinical events in adult patients

We assessed relationships between early peripheral blood type I interferons (IFN) levels, clinical new early warning scores (NEWS), and clinical outcomes in hospitalized coronavirus disease-19 (COVID-19) adult patients. Early IFN-β levels were lower among patients who further required intensive care unit (ICU) admission than those measured in patients who did not require an ICU admission during severe acute respiratory syndrome coronavirus type 2 infection. IFN-β levels were inversely correlated with NEWS only in the subgroup of patients who further required ICU admission. To assess whether peripheral blood IFN-β levels could be a potential relevant biomarker to predict further need for ICU admission, we performed receiver operating characteristic (ROC) curve analyses that showed for all study patients an area under ROC curve of 0.77 growing to 0.86 (p = 0.003) when the analysis was restricted to a subset of patients with NEWS ≥5 at the time of hospital admission. Overall, our findings indicated that early peripheral blood IFN-β levels might be a relevant predictive marker of further need for an ICU admission in hospitalized COVID-19 adult patients, specifically when clinical score (NEWS) was graded as upper than 5 at the time of hospital admission.     

The active role of interpreters in medical discourse – An observational study in emergency medicine

ObjectiveTo study communicative tasks executed and related strategies used by patients, health professionals, and medical interpreters.MethodsEnglish proficient and limited English proficient emergency department patients were observed. The content of patient-hospital staff communication was documented via pen and paper. Key themes and differences across interpreter types were established through qualitative analysis. Themes and differences across interpreter type were vetted and updated through member checking interviews.Results6 English proficient and 9 limited English proficient patients were observed. Key themes in communicative tasks included: establishing, maintaining, updating, and repairing understanding and rapport. All tasks were observed with English proficient and limited English proficient patients. The difference with limited English proficient patients was that medical interpreters played an active role in completing communicative tasks. Telephone-based interpreters faced challenges in facilitating communicative tasks based on thematic comparisons with in-person interpreters, including issues hearing and lost information due to the lack of visual cues.ConclusionsProfessional interpreters play an important role in communication between language discordant patients and health professionals that goes beyond verbatim translation.Practical implicationsTraining for interpreters and health professionals, and the design of tools for facilitating language discordant communication, should consider the role of interpreters beyond verbatim translation.     

Methicillin resistance is not a predictor of severity in community-acquired Staphylococcus aureus necrotizing pneumonia—results of a prospective observational study

Staphylococcal necrotizing pneumonia (NP) is a severe disease associated with Panton–Valentine leucocidin (PVL). NP was initially described for methicillin-susceptible Staphylococcus aureus (MSSA) infection, but cases associated with methicillin-resistant S. aureus (MRSA) infection have increased concomitantly with the incidence of community-acquired MRSA worldwide. The role of methicillin resistance in the severity of NP remains controversial. The characteristics and outcomes of 133 patients with PVL-positive S. aureus community-acquired pneumonia (CAP) were compared according to methicillin resistance. Data from patients hospitalized for PVL-positive S. aureus CAP in France from 1986 to 2010 were reported to the National Reference Centre for Staphylococci and were included in the study. The primary end point was mortality. Multivariate logistic modelling and the Cox regression were used for subsequent analyses. We analysed 29 cases of PVL-MRSA and 104 cases of PVL-MSSA pneumonia. Airway haemorrhages were more frequently associated with PVL-MSSA pneumonia. However, no differences in the initial severity or the management were found between these two types of pneumonia. The rate of lethality was 39% regardless of methicillin resistance. By Cox regression analysis, methicillin resistance was not found to be a significant independent predictor of mortality at 7 or 30 days (p 0.65 and p 0.71, respectively). Our study demonstrates that methicillin resistance is not associated with the severity of staphylococcal necrotizing pneumonia.     

Immune interventions in COVID-19: a matter of time?

As the COVID-19 pandemic is still ongoing, and considering the lack of efficacy of antiviral strategies to this date, and the reactive hyperinflammation leading to tissue lesions and pneumonia, effective treatments targeting the dysregulated immune response are more than ever required. Immunomodulatory and immunosuppressive drugs have been repurposed in severe COVID-19 with contrasting results. The heterogeneity in the timing of treatments administrations could be accountable for these discrepancies. Indeed, many studies included patients at different timepoints of infection, potentially hiding the beneficial effects of a time-adapted intervention. We aim to review the available data on the kinetics of the immune response in beta-coronaviruses infections, from animal models and longitudinal human studies, and propose a four-step model of severe COVID-19 timeline. Then, we discuss the results of the clinical trials of immune interventions with regards to the timing of administration, and finally suggest a time frame in order to delineate the best timepoint for each treatment.     

Considerable variation of trough β-lactam concentrations in older adults hospitalized with infection—a prospective observational study

In older adults, few studies confirm that adequate concentrations of antibiotics are achieved using current dosage regimens of intravenous β-lactam antibiotics. Our objective was to investigate trough concentrations of cefotaxime, meropenem, and piperacillin in older adults hospitalized with infection. We included 102 patients above 70 years of age. Total trough antibiotic concentrations were measured and related to suggested target intervals. Information on antibiotic dose, patient characteristics, and 28-day outcomes were collected from medical records and regression models were fitted. Trough concentrations for all three antibiotics exhibited considerable variation. Mean total trough concentrations for cefotaxime, meropenem, and piperacillin were 6.5 mg/L (range 0–44), 3.4 mg/L (range 0–11), and 30.2 mg/L (range 1.2–131), respectively. When a target range of non-species-related breakpoint ? 5× non-species-related breakpoint was applied, only 36% of patients had both values within the target range. Regression models revealed that severe sepsis was associated with varying concentration levels and increasing age and diminishing kidney function with high concentration levels. The study was not powered to demonstrate consequences in clinical outcomes. Conclusively, in older adults treated with cefotaxime, meropenem, or piperacillin-tazobactam, trough antibiotic concentrations varied considerably. Better predictors to guide dosing regimens of β-lactam antibiotics or increased use of therapeutic drug monitoring are potential ways to address such variations.     

Serum TGF-β as a predictive biomarker for severe disease and fatality of COVID-19

For targeted intervention in coronavirus disease 2019 (COVID-19), there is a high medical need for biomarkers that predict disease progression and severity in the first days after symptom onset. This study assessed the utility of early transforming growth factor β (TGF-β) serum levels in COVID-19 patients to predict disease severity, fatality, and response to dexamethasone therapy. Patients with severe COVID-19 had significantly higher TGF-β levels (416 pg/mL) as compared to patients with mild (165 pg/mL, p < 0.0001) or moderate COVID-19 (241 pg/mL; p < 0.0001). Receiver operating characteristics area under the curve values were 0.92 (95% confidence interval [CI] 0.85–0.99, cut-off: 255 pg/mL) for mild versus severe COVID-19, and 0.83 (95% CI 0.65–1.0, cut-off: 202 pg/mL) for moderate versus severe COVID-19. Patients who died of severe COVID-19 had significantly higher TGF-β levels (453 pg/mL) as compared to convalescent patients (344 pg/mL), and TGF-β levels predicted fatality (area under the curve: 0.75, 95% CI 0.53–0.96). TGF-β was significantly reduced in severely ill patients treated with dexamethasone (301 pg/mL) as compared to untreated patients (416 pg/mL; p < 0.05). Early TGF-β serum levels in COVID-19 patients predict, with high accuracy, disease severity, and fatality. In addition, TGF-β serves as a specific biomarker to assess response to dexamethasone treatment.     

SARS-CoV-2 –RNA persists longer in faecal sample as compared to nasal and throat swab samples of COVID-19 patients’; an observational study

The route of transmission of Novel SARS-CoV-2 virus is ambiguous. In this regard we planned a study to find out SARS-CoV-RNA shedding in various clinical samples of 9 COVID-19 positive patients. SARS-CoV-RNA was detected in nasal swab (NS), throat swab (TS) and faecal sample but was not detected in serum and urine samples. We also report that SARS-CoV-2-RNA persisted in faeces for >20 days. Persistence of faecal RNA might impose challenge in infection control and the disease may spread to household contacts if discharged. Perineal cleaning and hygiene may be advised at the time of vaginal delivery.     

Cryptococcal infection in HIV-infected patients with CD4+ T-cell counts under 100/μL diagnosed in a high-income country: a multicentre cohort study

ObjectivesThe World Health Organization recommends routinely screening HIV-infected patients with CD4⁺ T-cell counts <100/μL for cryptococcal infection to prevent cryptococcal meningitis (CM), based on studies in Sub-Saharan Africa where the prevalence of positive cryptococcal antigen (CrAg+) is ≥ 3% in this subgroup. Data about such prevalence in Spain are unavailable and rare in other European countries. Thus, the Spanish AIDS Study Group guidelines do not recommend routinely screening. We aim to determine the prevalence and outcomes of cryptococcal infection in this subgroup of patients in Spain.MethodsWe determined CrAg using a lateral flow assay in banked plasma from participants in the cohort of the Spanish AIDS Research Network. Eligible patients had CD4⁺ T-cell counts ≤100/μL at the time of plasma collection and a follow-up >4 weeks, unless they died.ResultsWe included 576 patients from June 2004 to December 2017. Of these, 43 were CrAg+ for an overall prevalence of 7.5%. There were no differences depending on birthplace. The CrAg+ was independently associated with a higher mortality at eight weeks (hazard ratio (HR) 5.36, 95% confidence interval (CI) 1.46–19.56) and 6 months (HR 3.12, 95% CI 1.19–8.21). CM was reported in 10 of the 43 CrAg+ patients. There were no cases among negatives. Five patients had CM when the plasma was collected and five developed it during the follow-up. The number of subjects needed to screen to anticipate the diagnosis of one CM case was 114.ConclusionsThe CrAg+ prevalence among HIV-infected patients with CD4⁺ T-cell counts ≤100/μL diagnosed in Spain, both immigrants and native-born Spanish, is >7%. Consequently, the Spanish AIDS Study Group guidelines have to be updated and recommend routine screening for cryptococcal infection in these patients. Future studies should explore whether this recommendation could be firmly applied to other European populations.     

Do integrated record systems lead to integrated services? An observational study of a multi-professional system in a diabetes service

Purpose

There are few opportunities to study the use of integrated electronic health record (EHR) systems, where single patient records are used by a number of health care staff. The purpose of the study was to understand how an integrated electronic health record system was used by health care staff in the treatment and management of diabetes patients. The investigation was focused on the interface between the primary and secondary care services which patients access for their diabetes care.

Methods

Observations of the use of an integrated electronic health record during patients’ consultations with health care staff were conducted over a three month period. Twelve patients were followed through their consultations with a range of health care staff at a secondary care Diabetes Centre and in primary care settings. A thematic analysis of the observation data was undertaken.

Results

The integrated electronic health record system had been implemented across the primary and secondary care interface and was used by many, but not all, clinicians involved in the care of patients with diabetes. In some areas of care it enabled health care staff to access more accurate and detailed information to inform their clinical decision-making. Issues including negotiating rules for accessing patient records and duplication of recording in paper record systems had not been resolved consistently across services.

Conclusions

The findings offer suggestive evidence that a shared electronic health record can support more integrated care. Unresolved issues in implementing the system across all services and settings highlight the governance problems that can arise when systems are developed locally but are then extended across organisational and professional boundaries.     

Are coinfections with COVID-19 and influenza low or underreported? An observational study examining current published literature including three new unpublished cases

As the coronavirus disease-2019 (COVID-19) pandemic continues, one major point of uncertainty is the impact this novel pathogen will have during the upcoming 2020 to 2021 flu season. While the influenza virus is a known contributor to human morbidity and mortality, the question of how a coinfection between COVID-19 and influenza might manifest is of utmost concern. The aim of this study was to review the limited cases of COVID-19/influenza coinfection currently available in the literature, along with cases in the community of El Paso, TX, to determine whether any patterns of clinical presentation and morbidity emerged. An international review of the literature was conducted. Six published articles describing COVID-19/influenza coinfection were identified, with a total of 13 patients described therein. Three additional patients were identified from the El Paso, TX data. The most common presenting symptoms were fever and cough. The most common laboratory findings were elevated C-reactive protein and lymphocytopenia. Thirteen patients presented with viral pneumonia findings on CT, and nine had findings of ground-glass opacity. Finally, complications were reported in six patients, with most common complication being acute respiratory distress syndrome. The results of the review indicate that, due to the similarity in presentation between COVID-19 and influenza, further analysis will be required to understand the effects of coinfection on morbidity and mortality. However, the limited number of coinfection cases in the literature indicates that the implementation of COVID-19 control measures may continue to play a role in limiting the spread of these human respiratory pathogens.     

Early administration of tocilizumab in hospitalized COVID-19 patients with elevated inflammatory markers; COVIDSTORM—a prospective,randomized, single-centre,open-label study

ObjectivesSevere COVID-19 is associated with an imbalanced immune response. We hypothesized that patients with enhanced inflammation, as demonstrated by increased levels of certain inflammatory biomarkers, would benefit from interleukin-6 blockage.MethodsPatients hospitalized with COVID-19, hypoxemia, and at least two of four markedly elevated markers of inflammation (interleukin-6, C-reactive protein, ferritin, and/or D-dimer) were randomized for tocilizumab (TCZ) plus standard of care (SoC) or SoC alone. The primary endpoint was clinical status at day 28 assessed using a seven-category ordinal scale, and the secondary endpoints included intensive care unit admission, respiratory support, and duration of hospital admission.ResultsClinical status at day 28 was significantly better in patients who received TCZ in addition to SoC compared with those who received SoC alone (p = 0.037). By then, 93% of patients who received TCZ (n = 53 of 57) and 86% of control patients (n = 25 of 29) had been discharged from the hospital. In addition, 47% of TCZ patients (n = 27 of 57) and 24% of control patients (n = 7 of 29) had resumed normal daily activities. The median length of hospitalization was 9 days (interquartile range, 7–12) in the TCZ group and 12 days (interquartile range, 9–15) in the control group (p = 0.014).DiscussionIn patients hospitalized with COVID-19, hypoxemia, and elevated inflammation markers, administration of TCZ in addition to SoC was associated with significantly better clinical recovery by day 28 and a shorter hospitalization compared with SoC alone.     

Efficacy of a self-management program for childhood asthma–: A prospective controlled study

Asthma training programs for parents and children have been developed to increase both the self-management skills of asthmatic children and compliance with medical regimes. In order to evaluate two training programs for asthmatic children aged 7–14, 81 patients were randomly assigned to three groups. Group 1 consisted of 27 patients and their parents who participated in a five-day standardized family-oriented clinical asthma training program. They had monthly follow-up meetings with the training team for a period of six months. Group 2 (n=29) had the same clinical training without follow-up interventions; a control group (n=25) received regular medical treatment according to the international guidelines at the asthma clinics without a training program and served as control group. Questionnaires regarding self-management aspects, coping and anxiety were filled out by patients, parents, family doctors and the training team prior to as well as twelve months after the training. The results indicate that Training group 1 benefitted most with respect to active asthma self-management, Training group 2 to some degree while the control group showed no significant effects. The differences after one year between the three groups regarding physical parameters such as lung-function and days missed in school did not reach the level of significance. Our results indicate that the long-term efficacy of self management courses for asthmatic children is enhanced by regular follow-up training sessions.     

Parkinson’s disease: Content analysis of patient online discussion forums. A prospective observational study using Netnography

ObjectivesTo assess the users' characteristics, discussion contents, and the atmosphere of virtual peer communities.MethodsA qualitative, prospective study was conducted using the Netnography method. The most popular, publicly accessible French discussion forums were investigated. The web users’ quotes were collected from May to October 2018. Data analysis triangulation was performed by two researchers using the NVivo 12® software.ResultsThe users discussed their experience with Parkinson’s disease (PD) in a warm atmosphere. 23 discussion threads were analysed: 302 messages posted by 70 users (70% were females; the average illness duration was 6 years); 115 encoded nodes were created. Five user profiles appeared: leader, follower, expert, mixed, and undetermined. Common preoccupations were a lack of time and listening from the physicians’ side. Three themes emerged: managing symptoms, living with PD, and sharing illness experiences. Users sought actively for a cure to limit or stop disease evolution, using alternative and complementary therapies to optimize their daily condition.ConclusionsOnline forums foster person’s informal learnings about coping with PD. Healthcare professionals can use these learnings to optimize person-centred support.Practice implicationsDuring consultations, healthcare professionals should invite persons to discuss their online activity, informal learnings, beliefs and expectations towards therapeutic strategies.     

Early postoperative bleeding after isolated coronary bypasses: Changes over a period of 20 years – An observational study

ObjectivesThe objectives were to analyze the evolution of the postoperative bleeding after coronary artery bypass grafting and to determine which factors impacted on this evolution.MethodsThis is a single-center retrospective study including 4590 patients undergoing coronary bypass surgery between 1995 and 2017. The study period was divided into 3 same-sized periods. We analyzed the evolution of the bleeding according to: the chest volume bleeding over the first 24 hours, the severity and the rate of transfusion during the hospital stay. Intrahospital outcomes were compared between “minor” and “major” bleedings. The risk factors of major bleeding were analyzed by multiple logistic regression.ResultsThe chest volume decreased particularly during the first years of the study period. Major bleedings decreased over the periods (7.3%, 4.9% and 3.8% respectively, P < 0.0001), as did the rate of transfusion (26.4%, 23.5% and 19.6% respectively, P < 0.0001). Major bleedings were correlated with hospital mortality (8.2% versus 1.1%, P < 0.0001). The risk factors of major bleeding were the period 1 (1995 to 2003), a renal failure, a resternotomy, the EuroSCORE, the hematocrit prior to cardiopulmonary bypass and the duration of cardiopulmonary bypass.ConclusionsPostoperative bleeding decreased mainly in the 1990s. Progressive changes in bleeding prevention and blood recovery, surgical techniques, haemoglobin threshold for transfusion decision and practitioners’ experience have contributed to these results and must be continued to optimize the postoperative outcomes.     

Shifts in patients’ question-asking behaviour between 2007 and 2016: An observational study of video-recorded general practice consultations

ObjectiveTo gain insight into patient participation in general practice by examining if and how patients’ question-asking behaviour has changed over the years (2007–2016).MethodsA random set of real-life video-recorded consultations collected in 2015–2016 (n = 437) was observed and compared with that of a former study in 2007–2008 (n = 533). Patients’ question-asking behaviour was coded using an adapted RIAS protocol containing six categories: medical condition/therapeutic regimen; psychosocial; social context; lifestyle; ask for opinion doctor; practical. GPs and patients completed questionnaires about their background characteristics. Data were analysed using multi-level analysis.ResultsPatients asked fewer questions in 2016 than in 2007. The type of question-asking behaviour changed significantly: in particular medical questions decreased while practical questions increased. Less educated patients asked significantly more practical questions than higher educated patients.ConclusionContrary to our expectations, patients’ question-asking has decreased in 2016 compared to 2007, while the average consultation length has increased. The type of questions shifted from medical to practical, especially in less educated patients. It seems that GPs’ professional role has expanded over time, since patients nowadays ask their GP more non-medical questions.Practice implicationsGPs probably could continue facilitating patient involvement by more frequently using partnership-building and supportive communication.     

How representative is a point-of-care randomized trial? Clinical outcomes of patients excluded from a point-of-care randomized controlled trial evaluating antibiotic duration for Gram-negative bacteraemia: a multicentre prospective observational cohort study

ObjectivesPatients included in randomized controlled trials (RCT) are poorly representative of the general population. We compared outcomes of patients excluded from the PIRATE trial, a point-of-care RCT evaluating antibiotic durations for Gram-negative bacteraemia, with those of enrolled patients.MethodsA prospective observational cohort study, ‘EPCO’ (Excluded Patients' Clinical Outcomes) included patients excluded from the PIRATE trial. As in PIRATE, whose patients were randomized to 7-day, 14-day, or C-reactive-protein (CRP)-guided antibiotic durations, EPCO's primary outcome was occurrence of clinical success at 30 days. We also compared baseline characteristics, outcome rates and treatment-effect estimates.ResultsIn all, 405 patients were included in EPCO and compared with the 503 PIRATE patients. Reasons for exclusion were mainly medical (317/405; 78%), the most frequent being complicated infection. Excluded patients had more co-morbidities (Charlson median 3 versus 1, p < 0.001). Bacteraemia was more often health-care-associated (26% versus 9%, p < 0.001). The 30-day success rate was significantly lower among EPCO patients (299/396; 76% versus 469/493; 95%, p < 0.001), but the success rate was not significantly different for those excluded for non-medical reasons (68/75; 91%, p 0.09). There was no significant difference in failure rates of EPCO patients according to their treatment duration (difference 7 days versus 14 days: p 0.75; 7 days versus CRP-correspondent: p 1.00; 14 days versus CRP-correspondent: p 1.00).ConclusionAlthough point-of-care-randomized trials are more inclusive and representative than traditional RCTs, they are still likely to select patients with lower failure risk. Shorter antibiotic durations were not associated with failure in either included or excluded patients, supporting the generalizability of the PIRATE trial's findings.     

Contribution of the FilmArray® Gastrointestinal Panel in the laboratory diagnosis of gastroenteritis in a cohort of children: a two-year prospective study

This study represents a 2-year picture of the epidemiology of enteric pathogens in children suffering from gastroenteritis using the FilmArray® Gastrointestinal Panel (FA-GP), a multiplex molecular assay that allows to simultaneously detect a large panel of pathogens independently of the etiological suspicion and to evaluate its potential contribution to the diagnosis compared to the conventional methods.A total of 1716 stool samples, collected from children with clinical suspicion of bacterial and/or viral gastroenteritis attending the University Hospital of Parma, was submitted to the FA-GP and, when an adequate aliquot was available, to electron microscopy (n = 1163) for virus detection and to an enterovirus-targeting real-time PCR (n = 1703). Specimens with positive results for Salmonella, Yersinia enterocolitica, Vibrio, diarrheagenic Escherichia coli/Shigella, Campylobacter, Plesiomonas shigelloides and/or parasites by the FA-GP were also submitted to conventional diagnostic methods.The FA-GP gave positive results in 958 (55.8%) cases, 64.8% from inpatients: 647 (67.5%) contained a single agent and 311 (32.5%) multiple agents, for a total of 1374 pathogens. Enteropathogenic E. coli, rotavirus, norovirus, toxigenic Clostridioides difficile, and sapovirus were the most commonly detected pathogens. A total of 812 additional agents (344 of which as single pathogen) was detected by the FA-GP and not included in the clinical suspicion. The overall recovery rate of the conventional methods from stools that resulted positive by the FA-GP was 38.6% for bacteria, 50% and 84.2% for Giardia intestinalis and Cryptosporidium, respectively, and ranged from 3.7% to 64.6% for viruses, if excluding all electron microscopy-negative astroviruses. Enterovirus, an agent not targeted by the FA-GP, was revealed in 9.6% (164/1703) of the examined samples, and in 52 cases it was the only agent detected.The results of this study allowed to extend the range of detectable pathogens independently of the clinical suspicion, to detect co-infections in almost one third of children positive for at least one agent and to show that conventional methods would have missed more than half of the enteric agents detected by the FA-GP.