Modelling the potential increase in eligible participants in clinical trials with inclusion of community intensive care unit patients in Alberta, Canada: a decision tree analysis.

PURPOSE: Critical care research in Canada is conducted primarily in academically affiliated intensive care units (ICUs) with established research infrastructure. Efforts are made to engage community hospital ICUs in research, although the impacts of their inclusion in clinical research have never been explicitly quantified. We therefore sought to determine the number of additional eligible patients that could be recruited into critical care trials and the change in time to study completion if community ICUs were included in clinical research. METHODS: We conducted a decision tree analysis using 2018 Alberta Health Services data. Patient demographics and clinical characteristics for all ICU patients were compared against eligibility criteria from ten landmark, randomized, multicentre critical care trials. Individual patients from academic and community ICUs were assessed for eligibility in each of the ten studies, and decision tree analysis models were built based on prior inclusion and exclusion criteria from those trials. RESULTS: The number of potentially eligible patients for the ten trials ranged from 2,082 to 10,157. Potentially eligible participants from community ICUs accounted for 40.0% of total potentially eligible participants. The recruitment of community ICU patients in trials would have increased potential enrolment by an average of 64.0%. The inclusion of community ICU patients was predicted to decrease time to trial completion by a mean of 14 months (43% reduction). CONCLUSION: Inclusion of community ICU patients in critical care research trials has the potential to substantially increase enrolment and decrease time to trial completion.

RéSUMé: OBJECTIF: La recherche en soins intensifs au Canada est principalement réalisée dans des unités de soins intensifs affiliées à des centres universitaires jouissant d'infrastructures de recherche bien établies. Des efforts ont été déployés pour engager les unités de soins intensifs des hôpitaux communautaires en recherche, mais les impacts de leur participation à la recherche clinique n'ont jamais été explicitement quantifiés. Nous avons conséquemment cherché à déterminer le nombre de patient·es additionnel·les pouvant être recruté·es dans des études de soins critiques ainsi que la variation du temps nécessaire pour compléter les études si la patientèle issue d'unités de soins intensifs d'hôpitaux communautaires participait à la recherche clinique. MéTHODE: Une analyse par arbre de décision a été réalisée à partir de données provenant des Alberta Health Services pour l'année 2018. Les données démographiques et les caractéristiques cliniques de tou·tes les patient·es admis·es aux soins intensifs ont été comparées avec les critères d'éligibilité de dix importantes études multicentriques, randomisées, contrôlées en soins intensifs. Les patient·es des unités de soins intensifs universitaires et communautaires ont tou·tes été évalué·es pour leur éligibilité à chacune des dix études, et des modèles d'arbres décisionnels ont été construits en se basant sur les critères originaux d'inclusion et d'exclusion. RéSULTATS: Le nombre de personnes potentiellement éligibles pour les dix études s'est situé entre 2082 et 10 157. Les patient·es potentiellement admissibles en provenance d'unités de soins intensifs communautaires ont représenté 40,0 % de toutes les personnes potentiellement admissibles. Le recrutement de patient·es en provenance d'unités de soins intensifs communautaires aurait permis une hausse moyenne du recrutement potentiel de 64,0 %. L'inclusion de patient·es des unités de soins intensifs communautaires pourrait également réduire le temps nécessaire à la complétion des études de 14 mois en moyenne (réduction de 43 %). CONCLUSION: L'inclusion de patient·es en provenance d'unités de soins intensifs d'hôpitaux communautaires dans la recherche clinique en soins critiques a le potentiel d'augmenter substantiellement le recrutement et de diminuer le temps nécessaire à la complétion des études.

Hyperammonemia syndrome post-lung transplantation: Case series and systematic review of literature.

BACKGROUND: Hyperammonemia syndrome (HS) is a rare post-transplant complication associated with high morbidity and mortality. Its incidence appears to be higher in lung transplant recipients and its pathophysiology is not well understood. In addition to underlying metabolic abnormalities, it is postulated that HS may be associated with Ureaplasma or Mycoplasma spp. lung infections. Management of this condition is not standardized and may include preemptive antimicrobials, renal replacement, nitrogen scavenging, and bowel decontamination therapies, as well as dietary modifications. METHODS: In this case series, we describe seven HS cases, five of whom had metabolic deficiencies ruled out. In addition, a literature review was performed by searching PubMed following PRISMA-P guidelines. Articles containing the terms "hyperammonemia" and "lung" were reviewed from 1 January 1997 to 31 October 2021. RESULTS: All HS cases described in our center had positive airway samples for Mycoplasmataceae, neurologic abnormalities and high ammonia levels post-transplant. Mortality in our group (57%) was similar to that published in previous cases. The literature review supported that HS is an early complication post-transplant, associated with Ureaplasma spp. and Mycoplasma hominis infections and of worse prognosis in patients presenting cerebral edema and seizures. CONCLUSION: This review highlights the need for rapid testing for Ureaplasma spp. and M. hominis after lung transplant, as well as the necessity for future studies to explore potential therapies that may improve outcomes in these patients.

Association between Mycoplasma and Ureaplasma airway positivity, ammonia levels, and outcomes post-lung transplantation: A prospective surveillance study.

Hyperammonemia syndrome (HS) is a rare complication with high mortality described after lung transplantation. Its pathophysiology is still unclear, but previous studies, including murine models, have linked the identification of Mycoplasmataceae in airway specimens with HS occurrence. This study explores the association between Mycoplasmataceae polymerase chain reaction (PCR) positivity, ammonia levels, HS, and mortality post-lung transplant. Adults who underwent lung transplantation between July 2017 and August 2019 had prospective surveillance testing for Mycoplasma and Ureaplasma using PCR on post-operative bronchoscopy samples. One hundred and fifty-nine patients underwent lung transplantation during the study period. Mean age was 54 (±13) years; baseline diseases were predominantly pulmonary fibrosis (37.7%) and chronic obstructive pulmonary disease (35.8%). Mycoplasma and/or Ureaplasma airway positivity was found in 42 (26.4%) of tested patients, represented mostly by M. salivarium (26/43; 60.4%), U. parvum (7/43; 16.2%), and U. urealyticum (5/43; 11.6%). Median peak ammonia levels were higher in those with Ureaplasma colonization compared to uncolonized patients (p = .04), however, only three patients developed HS. Recipient airway Ureaplasma positivity was independently associated with younger (aOR 0.94, 95% CI 0.88-0.99, p = .04) and female donors (aOR 4.29; 95% CI 1.01-18.2, p = .05).

Do COVID-19 Infections Result in a Different Form of Secondary Hemophagocytic Lymphohistiocytosis.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in significant morbidity and mortality across the world, with no current effective treatments available. Recent studies suggest the possibility of a cytokine storm associated with severe COVID-19, similar to the biochemical profile seen in hemophagocytic lymphohistiocytosis (HLH), raising the question of possible benefits that could be derived from targeted immunosuppression in severe COVID-19 patients. We reviewed the literature regarding the diagnosis and features of HLH, particularly secondary HLH, and aimed to identify gaps in the literature to truly clarify the existence of a COVID-19 associated HLH. Diagnostic criteria such as HScore or HLH-2004 may have suboptimal performance in identifying COVID-19 HLH-like presentations, and criteria such as soluble CD163, NK cell activity, or other novel biomarkers may be more useful in identifying this entity.

Sepsis in Traumatic Brain Injury: Epidemiology and Outcomes.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability. Risk factors for in-hospital mortality include older age, co-morbidity, and TBI severity. Few studies have investigated the role of sepsis in individuals with TBI. METHODS: We studied adult patients with TBI admitted to intensive care over a 5-year period. Patient characteristics were identified by linking clinical and administrative databases. Charts of individuals with TBI and sepsis were manually reviewed. Predictors of ICU and hospital mortality were identified using logistic regression modeling. RESULTS: Four hundred eighty-six individuals with TBI were admitted to intensive care. Sixteen (3.3%) developed sepsis. Pneumonia was the most common source (94%). Staphylococcus aureus was the most common pathogen (75%). ICU lengths of stay (LOS) (12.2 days [interquartile range (IQR) 4.4-23.5] versus 3.7 days [IQR 1.7-8.2]; p < 0.001) and hospital LOS (28.0 days [IQR 11.8-41.4] versus 15.3 days [IQR 5.0-30.9]; p = 0.017) were longer in patients with TBI and sepsis. Sepsis was not associated with ICU (adjusted odds ratio [aOR] 0.51; 95%CI 0.12-2.27; p = 0.38) or hospital (aOR 0.78; 95% CI 0.21-2.96; p = 0.78) mortality, though age (aOR 1.02; 95% CI 1.00-1.04; p = 0.014 for hospital mortality), severe TBI (aOR 3.71; 95% CI 1.52-9.08; p = 0.004 for ICU mortality and 4.10; 95% CI 1.95-8.65; p < 0.001 for hospital mortality), and APACHE II score (aOR 1.19; 95% CI 1.11-1.28; p < 0.001 for ICU mortality and 1.22; 95% CI 1.14-1.31; p < 0.001 for hospital mortality) were. CONCLUSION: Sepsis in patients with TBI was not associated with mortality; however, sepsis was associated with increased health care utilization (ICU and hospital LOS).

Epidemiology and Outcomes in Critically Ill Patients with Human Immunodeficiency Virus Infection in the Era of Combination Antiretroviral Therapy.

Purpose. The impact of critical illness on survival of HIV-infected patients in the era of antiretroviral therapy remains uncertain. We describe the epidemiology of critical illness in this population and identify predictors of mortality. Materials and Methods. Retrospective cohort of HIV-infected patients was admitted to intensive care from 2002 to 2014. Patient sociodemographics, comorbidities, case-mix, illness severity, and 30-day mortality were captured. Multivariable Cox regression analyses were performed to identify predictors of mortality. Results. Of 282 patients, mean age was 44 years (SD 10) and 169 (59%) were male. Median (IQR) CD4 count and plasma viral load (PVL) were 125 cells/mm3 (30-300) and 28,000 copies/mL (110-270,000). Fifty-five (20%) patients died within 30 days. Factors independently associated with mortality included APACHE II score (adjusted hazard ratio [aHR] 1.12; 95% CI 1.08-1.16; p < 0.001), cirrhosis (aHR 2.30; 95% CI 1.12-4.73; p = 0.024), coronary artery disease (aHR 6.98; 95% CI 2.20-22.13; p = 0.001), and duration of HIV infection (aHR 1.07 per year; 95% CI 1.02-1.13; p = 0.01). CD4 count and PVL were not associated with mortality. Conclusions. Mortality from an episode of critical illness in HIV-infected patients remains high but appears to be driven by acute illness severity and HIV-unrelated comorbid disease rather than degree of immune suppression.

Macrolides and mortality in critically ill patients with community-acquired pneumonia: a systematic review and meta-analysis.

OBJECTIVE: Some studies suggest better outcomes with macrolide therapy for critically ill patients with community-acquired pneumonia. To further explore this, we performed a systematic review of studies with mortality endpoints that compared macrolide therapy with other regimens in critically ill patients with community-acquired pneumonia. DATA SOURCES: Studies were identified via electronic databases, grey literature, and conference proceedings through May 2013. STUDY SELECTION: Using prespecified criteria, two reviewers selected studies; studies of outpatients and hospitalized noncritically ill patients were excluded. DATA EXTRACTION: Two reviewers extracted data and evaluated bias using the Newcastle-Ottawa Scale. Random effects models were used to generate pooled risk ratios and evaluate heterogeneity (I). DATA SYNTHESIS: Twenty-eight observational studies (no randomized control trials) were included. Average age ranged from 58 to 78 years and 14-49% were women. In our primary analysis of 9,850 patients, macrolide use was associated with statistically significant lower mortality compared with nonmacrolides (21% [846 of 4,036 patients] vs 24% [1,369 of 5,814]; risk ratio, 0.82; 95% CI, 0.70-0.97; p = 0.02; I = 63%). When macrolide monotherapy was excluded, the macrolide mortality benefit was maintained (21% [737 of 3,447 patients] vs 23% [1,245 of 5,425]; risk ratio, 0.84; 95% CI, 0.71-1.00; p = 0.05; I = 60%). When broadly guideline-concordant regimens were compared, there was a trend to improved mortality and heterogeneity was reduced (20% [511 of 2,561 patients] mortality with beta-lactam/macrolide therapy vs 23% [386 of 1,680] with beta-lactam/fluoroquinolone; risk ratio, 0.83; 95% CI, 0.67-1.03; p = 0.09; I = 25%). When adjusted risk estimates were pooled from eight studies, macrolide therapy was still associated with a significant reduction in mortality (risk ratio, 0.75; 95% CI, 0.58-0.96; p = 0.02; I = 57%). CONCLUSIONS: In observational studies of almost 10,000 critically ill patients with community-acquired pneumonia, macrolide use was associated with a significant 18% relative (3% absolute) reduction in mortality compared with nonmacrolide therapies. After pooling data from studies that provided adjusted risk estimates, an even larger mortality reduction was observed. These results suggest that macrolides be considered first-line combination treatment in critically ill patients with community-acquired pneumonia and support current guidelines.

Community-acquired pneumonia.

PURPOSE OF REVIEW: This review examines the epidemiology, diagnosis, prognosis, treatment and prevention of community-acquired pneumonia (CAP) in adults. RECENT FINDINGS: CAP is a significant cause of morbidity and mortality. Streptococcus pneumoniae is the most common CAP pathogen; however, microbial cause varies by geographic location and host factors. Identification of a microbial cause in CAP remains challenging - 30-65% of cases do not have a pathogen isolated. The use of molecular techniques in addition to culture, serology and urinary antigen testing has improved diagnostic yield. Scoring systems are useful for CAP prognostication and site of care decisions. Studies evaluating novel biomarkers including pro-B-type natriuretic peptide and procalcitonin suggest potential adjunctive roles in CAP prognosis. Guideline-based treatment for CAP has changed little in recent years. Effective and timely antimicrobial therapy is crucial in optimizing outcomes and should be based on local antimicrobial susceptibility patterns. Macrolides may have additional anti-inflammatory properties and a mortality benefit in severe CAP. Preventive strategies include immunization and modification of specific patient risk factors. SUMMARY: CAP is common and causes considerable morbidity and mortality. A comprehensive approach including advanced diagnostic testing, effective and timely antimicrobial therapy and prevention is required to optimize CAP outcomes.

Macrolide use in the treatment of critically ill patients with pneumonia: Incidence, correlates, timing and outcomes.

BACKGROUND: Macrolide antibiotics are commonly used to treat pneumonia despite increasing antimicrobial resistance. Evidence suggests that macrolides may also decrease mortality in severe sepsis via immunomodulatory properties. OBJECTIVE: To evaluate the incidence, correlates, timing and mortality associated with macrolide-based treatment. METHODS: A population-based cohort of critically ill adults with pneumonia at five intensive care units in Edmonton, Alberta, was prospectively followed over two years. Data collected included disease severity (Acute Physiology and Chronic Health Evaluation [APACHE] II score), pneumonia severity (Pneumonia Severity Index score), comorbidities, antibiotic treatments at presentation and time to effective antibiotic. The independent association between macrolide-based treatment and 30-day all-cause mortality was examined using multivariable Cox regression. A secondary exploratory analysis examined time to effective antimicrobial therapy. RESULTS: The cohort included 328 patients with a mean Pneumonia Severity Index score of 116 and a mean APACHE II score of 17; 84% required invasive mechanical ventilation. Ninety-one (28%) patients received macrolide-based treatments, with no significant correlates of treatment except nursing home residence (15% versus 30% for nonresidents [P=0.02]). Overall mortality was 54 of 328 (16%) at 30 days: 14 of 91 (15%) among patients treated with macrolides versus 40 of 237 (17%) for nonmacrolides (adjusted HR 0.93 [95% CI 0.50 to 1.74]; P=0.8). Patients who received effective antibiotics within 4 h of presentation were less likely to die than those whose treatment was delayed (14% versus 17%; adjusted HR 0.50 [95% CI 0.27 to 0.94]; P=0.03). CONCLUSIONS: Macrolide-based treatment was not associated with lower 30-day mortality among critically ill patients with pneumonia, although receipt of effective antibiotic within 4 h was strongly predictive of survival. Based on these results, timely effective treatment may be more important than choice of antibiotics.

HISTORIQUE: Les macrolides sont souvent utilisés pour soigner la pneumonie, malgré une résistance croissante aux antimicrobiens. Selon les données probantes, les macrolides réduiraient également la mortalité en cas de septicémie sévère, en raison de ses propriétés immunomodulatoires. OBJECTIF: Évaluer l'incidence, les corrélats, les délais et la mortalité associés à un traitement fondé sur les macrolides. MÉTHODOLOGIE: Pendant deux ans, les chercheurs ont procédé au suivi rétrospectif d'une cohorte en population d'adultes atteints d'une grave pneumonie, hospitalisés dans cinq unités de soins intensifs d'Edmonton, en Alberta. Ils ont colligé la gravité de la maladie (indice APACHE II d'évaluation de la physiologie aiguë et de la santé chronique), la gravité de la pneumonie (indice de gravité de la pneumonie), les comorbidités, les traitements antibiotiques à la présentation et le délai avant la prise efficace d'antibiotiques. Ils ont examiné l'association indépendante entre le traitement aux macrolides et le décès au bout de 30 jours toutes causes confondues au moyen de la régression de Cox multivariable. Ils ont utilisé une analyse exploratoire secondaire pour examiner le délai avant un traitement antimicrobien efficace. RÉSULTATS: La cohorte se composait de 328 patients dont l'indice moyen de gravité de la pneumonie se situait à 116 et l'indice APACHE II moyen à 17; 84 % d'entre eux ont eu besoin d'une ventilation mécanique. Quatre-vingt-onze patients (28 %) ont reçu des traitements aux macrolides, sans corrélats significatifs du traitement à part le fait d'habiter dans un centre d'hébergement et de soins de longue durée (15 % par rapport à 30 % pour les non-résidents [P=0,02]). La mortalité globale correspondait à 54 cas sur 328 patients (16 %) au bout de 30 jours, soit 14 des 91 patients (15 %) traités aux macrolides par rapport à 40 des 237 (17 %) n'en ayant pas pris (RR rajusté de 0,93 [95 % IC 0,50 à 1,74]; P=0,8). Les patients qui prenaient des antibiotiques efficaces dans les quatre heures suivant leur présentation étaient moins susceptibles de mourir que ceux dont le traitement était retardé (14 % par rapport à 17 %; RR rajusté 0,50 [95 % IC 0,27 à 0,94]; P=0,03). CONCLUSIONS: Le traitement aux macrolides ne s'associait pas à une réduction du taux de mortalité au bout de 30 jours chez les patients atteints d'une grave pneumonie, mais la prise d'antibiotiques efficaces dans les quatre heures était fortement prédictive de la survie. D'après ces résultats, l'administration rapide d'un traitement efficace serait plus importante que le choix d'antibiotique.

Antimicrobial stewardship, procalcitonin testing, and rapid blood-culture identification to optimize sepsis care in critically ill adult patients: A quality improvement initiative.

We examined the effect of an antimicrobial stewardship program (ASP), procalcitonin testing and rapid blood-culture identification on hospital mortality in a prospective quality improvement project in critically ill septic adults. Secondarily, we have reported antimicrobial guideline concordance, acceptance of ASP interventions, and antimicrobial and health-resource utilization.

Macrolide-based regimens and mortality in hospitalized patients with community-acquired pneumonia: a systematic review and meta-analysis.

BACKGROUND: Macrolides are used to treat pneumonia despite increasing antimicrobial resistance. However, the immunomodulatory properties of macrolides may have a favorable effect on pneumonia outcomes. Therefore, we systematically reviewed all studies of macrolide use and mortality among patients hospitalized with community-acquired pneumonia (CAP). METHODS: All randomized control trials (RCTs) and observational studies comparing macrolides to other treatment regimens in adults hospitalized with CAP were identified through electronic databases and gray literature searches. Primary analysis examined any macrolide use and mortality; secondary analysis compared Infectious Diseases Society of America/American Thoracic Society guideline-concordant macrolide/beta-lactam combinations vs respiratory fluoroquinolones. Random effects models were used to generate pooled risk ratios (RRs) and evaluate heterogeneity (I(2)). RESULTS: We included 23 studies and 137,574 patients. Overall, macrolide use was associated with a statistically significant mortality reduction compared with nonmacrolide use (3.7% [1738 of 47,071] vs 6.5% [5861 of 90,503]; RR, 0.78; 95% confidence interval [CI], .64-.95; P = .01; I(2)= 85%). There was no survival advantage and heterogeneity was reduced when analyses were restricted to RCTs (4.6% [22 of 479] vs 4.1% [25 of 613]; RR, 1.13; 95% CI, .65-1.98; P = .66; I(2)= 0%) or to patients treated with guideline-concordant antibiotics (macrolide/beta-lactam, 5.3% [297 of 5574] vs respiratory fluoroquinolones, 5.8% [408 of 7050]; RR, 1.17; 95% CI, .91-1.50; P = .22; I(2)= 43%). CONCLUSIONS: In hospitalized patients with CAP, macrolide-based regimens were associated with a significant 22% reduction in mortality compared with nonmacrolides; however, this benefit did not extend to patients studied in RCTs or patients that received guideline-concordant antibiotics. Our findings suggest guideline concordance is more important than choice of antibiotic when treating CAP.

Defining COVID-19-associated pulmonary aspergillosis: systematic review and meta-analysis.

BACKGROUND: Pulmonary aspergillosis may complicate coronavirus disease 2019 (COVID-19) and contribute to excess mortality in intensive care unit (ICU) patients. The disease is poorly understood, in part due to discordant definitions across studies. OBJECTIVES: We sought to review the prevalence, diagnosis, treatment, and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) and compare research definitions. DATA SOURCES: PubMed, Embase, Web of Science, and MedRxiv were searched from inception to October 12, 2021. STUDY ELIGIBILITY CRITERIA: ICU cohort studies and CAPA case series including ≥3 patients were included. PARTICIPANTS: Adult patients in ICUs with COVID-19. INTERVENTIONS: Patients were reclassified according to four research definitions. We assessed risk of bias with an adaptation of the Joanna Briggs Institute cohort checklist tool for systematic reviews. METHODS: We calculated CAPA prevalence using the Freeman-Tukey random effects method. Correlations between definitions were assessed with Spearman's rank test. Associations between antifungals and outcome were assessed with random effects meta-analysis. RESULTS: Fifty-one studies were included. Among 3297 COVID-19 patients in ICU cohort studies, 313 were diagnosed with CAPA (prevalence 10%; 95% CI 8%-13%). Two hundred seventy-seven patients had patient-level data allowing reclassification. Definitions had limited correlation with one another (ρ = 0.268-0.447; p < 0.001), with the exception of Koehler and Verweij (ρ = 0.893; p < 0.001); 33.9% of patients reported to have CAPA did not fulfill any research definitions. Patients were diagnosed after a median of 8 days (interquartile range 5-14) in ICUs. Tracheobronchitis occurred in 3% of patients examined with bronchoscopy. The mortality rate was high (59.2%). Applying CAPA research definitions did not strengthen the association between mould-active antifungals and survival. CONCLUSIONS: The reported prevalence of CAPA is significant but may be exaggerated by nonstandard definitions.

How important is age in defining the prognosis of patients with community-acquired pneumonia?

PURPOSE OF REVIEW: Given that the population is increasing in age, a better understanding of the relationship between chronological age and health-related outcomes (especially mortality) is needed, for both chronic diseases (e.g. diabetes) and acute illnesses (e.g. pneumonia). Our purpose was to review the impact of age on the prognosis of patients with community-acquired pneumonia (CAP). RECENT FINDINGS: Many studies in patients with CAP have suggested that chronological age is not necessarily independently associated with mortality. Poorer outcomes in the elderly with CAP have been related to severity of disease, comorbid disease burden, functional status, and frailty, but not to age alone. However, many of these studies suffer from 'over-adjustment' due to the use of unmodified severity scores such as the Pneumonia Severity Index or Acute Physiology and Chronic Health Evaluation II (that already include age) in multivariable analyses. Studies accounting for this over-adjustment suggest that age is, in fact, independently associated with mortality in hospitalized patients with CAP. Other outcomes including hospitalization and readmission rates, hospital length of stay, and cost of care are similarly associated with increasing age. Residual confounding is still a problem in many of the observational studies reviewed. SUMMARY: Contrary to conventional wisdom, chronological age is independently associated with adverse outcomes in patients with CAP. Until better methods (or more clinically-rich datasets) for observational studies are developed that can avoid over-adjustment and better deal with residual confounding, physicians should take into account both a patient's overall health status and his or her chronological age.

Procalcitonin measurement in West Nile virus neuroinvasive disease: A first case series.

West Nile virus neuroinvasive disease (WNV-NID) is challenging to diagnose. Procalcitonin (PCT) is a useful diagnostic test to identify bacterial infections. We present four cases of WNV-NID with serum PCT measurements. Methods: Daily (days 1-7) serum PCT (bioMérieux) was examined for critically ill patients with sepsis enrolled in a provincial sepsis study. Patients with identified WNV-NID are descriptively analyzed in this case series. PCT values of ≥0.5 ng/mL were suggestive of bacterial infection. Results: Four patients with WNV-NID were identified. Those with viral infections alone had consistently low PCT values ranging from 0.09 ng/mL to 0.34 ng/mL. Those with documented bacterial co-infections had initially elevated PCT levels that decreased by more than 50% with antimicrobial therapy. Conclusion: These cases are the first to report serial PCT measurements in confirmed cases of WNV-NID and support a low serum PCT in WNV-NID.

La maladie neuro-invasive causée par le virus du Nil occidental (MNI-VNO) est difficile à diagnostiquer. La procalcitonine (PCT) est un test diagnostique utile pour dépister les infections bactériennes. Les auteurs présentent quatre cas de MNI-VNO assortis de mesures de PCT sérique. Méthodologie : Les chercheurs ont procédé à l'examen quotidien (jours 1 à 7) du PCT sérique (bioMérieux) chez des patients gravement malades et atteints de sepsis recrutés dans une étude provinciale du sepsis. Les patients retenus à cause d'une MNI-VNO établie font l'objet d'une analyse descriptive dans cette série de cas. Les valeurs de PCT de 0,5 ng/mL ou plus étaient évocatrices d'une infection bactérienne. Résultats : Quatre patients atteints d'une MNI-VNO ont été retenus. Ceux qui n'étaient atteints que d'une infection virale obtenaient des valeurs de PCT faibles, de 0,09 ng/mL à 0,34 ng/mL. Ceux qui étaient atteints de co-infections bactériennes démontrées commençaient par obtenir des taux élevés de PCT, qui diminuaient de plus de 50 % après un traitement antimicrobien. Conclusion : Ces cas sont les premiers à faire état des mesures sérielles de la PCT dans des cas confirmés de MNI-VNO et à soutenir une faible PCT sérique en présence de MNI-VNO.

Outcomes among critically ill adults with influenza infection.

Background: Influenza infection is a major cause of mortality in critical care units. Methods: ata on critically ill adult patients with influenza infection from 2014 to 2019 were retrospectively collected, including mortality and critical care resource utilization. Independent predictors of mortality were identified using Cox regression. Results: ne hundred thirty patients with confirmed influenza infection had a mean age of 56 (SD 16) years; 72 (55%) were male. Mean Acute Physiology and Chronic Health Evaluation (APACHE II) score was 22 (SD 9). One hundred eight (83%) patients had influenza A (46% H1N1pdm09, 33% H3N2); 21 (16%) had influenza B. Fifty-five (42%) patients had bacterial co-infection. Only 5 (4%) had fungal co-infection. One hundred eight (83%) patients required mechanical ventilation; 94 (72%), vasopressor support; 26 (20%), continuous renal replacement therapy (CRRT); and 11 (9%), extracorporeal membrane oxygenation. One hundred twenty one (93%) patients received antiviral therapy (median 5 d). Thirty-day mortality was 23%. Patients who received antiviral treatment were more likely to survive with an adjusted hazard ratio (aHR) of 0.15 (95% CI 0.04 to 0.51, p = 0.003). Other independent predictors of mortality were the need for CRRT (aHR 2.48, 95% CI 1.14 to 5.43, p = 0.023), higher APACHE II score (aHR 1.08, 95% CI 1.02 to 1.14, p = 0.011), and influenza A (aHR 7.10, 95% CI 1.37 to 36.8, p = 0.020) compared with influenza B infection. Conclusions: mong critically ill influenza patients, antiviral therapy was independently associated with survival. CRRT, higher severity of illness, and influenza A infection were associated with mortality.

Historique: L'infection par l'influenza est une cause majeure de décès en soins intensifs. Méthodologie: Les chercheurs ont procédé à la collecte rétrospective des données sur des patients adultes gravement malades à cause d'une infection par l'influenza entre 2014 et 2019, y compris la mortalité et l'utilisation des ressources en soins intensifs. Ils ont établi les prédicteurs indépendants de mortalité au moyen de la régression de Cox. Résultats: Les 130 patients atteints d'une infection confirmée par l'influenza avaient un âge moyen de 56 ans (±16), et 72 (55 %) étaient de sexe masculin. Le score APACHE II (acronyme anglais d'évaluation de la physiologie aiguë et de la santé chronique) s'élevait à 22 (±9). Au total, 108 patients (83 %) étaient atteints de la grippe de type A (46 % H1N1pdm09, 33 % H3N2) et 21 (16 %), de la grippe de type B. De plus, 55 patients (42 %) étaient atteints d'une co-infection bactérienne, et seulement cinq (4 %), d'une co-infection fongique. Par ailleurs, 108 patients (83 %) ont eu besoin de ventilation mécanique, 94 (72 %), d'un soutien vasopresseur; 26 (20 %), d'une thérapie continue de remplacement rénal (TCRR) et 11 (9 %), d'une oxygénation extracorporelle. Au total, 121 patients (93 %) ont reçu une antivirothérapie (pendant une période médiane de cinq jours). La mortalité au bout de 30 jours s'élevait à 23 %. Les patients qui avaient reçu une antivirothérapie étaient plus susceptibles de survivre, selon un risque relatif ajusté (RRa) de 0,15 (IC à 95 % : 0,04 à 0,51, p = 0,003). Il y avait d'autres prédicteurs indépendants de mortalité : la nécessité de recourir à une TCRR (RRa 2,48, IC à 95 % : 1,14 à 5,43, p = 0,023), un score APACHE II élevé (RRa 1,08, IC à 95 % : 1,02 à 1,14, p = 0,011) et l'infection par l'influenza de type A (RRa 7,10, IC à 95 % : 1,37 à 36,8, p = 0,020) plutôt que par l'influenza de type B. Conclusions: Chez les patients gravement malades atteints de l'influenza, l'antivirothérapie était associée de manière indépendante à la survie. La TCRR, la plus grande gravité de la maladie et l'infection par l'influenza de type A étaient liées à la mortalité.

Detection of SARS-CoV-2 antibodies formed in response to the BNT162b2 and mRNA-1237 mRNA vaccine by commercial antibody tests.

BACKGROUND: With rapid approval of SARS-CoV-2 vaccines, the ability of clinical laboratories to detect vaccine-induced antibodies with available high-throughput commercial assays is unknown. We aimed to determine if commercial serology assays can detect vaccine-induced antibodies (VIAs) and understand the vaccination response. METHODS: This cohort study recruited healthcare workers and residents of long-term care facilities (receiving the BNT162b2 and mRNA-1273 products, respectively) who underwent serum collection pre-vaccination (BNT162b2 group), 2-weeks post vaccination (both groups), and pre-2nd dose (both groups). Sera were tested for the presence of SARS-CoV-2 IgG using four commercial assays (Abbott SARS-CoV-2 IgG, Abbott SARS-CoV-2 IgG II Quant, DiaSorin Trimeric S IgG, and GenScript cPASS) to detect VIAs. Secondary outcomes included description of post-vaccination antibody response and correlation with neutralizing titers. RESULTS: 225 participants (177 receiving BNT162b2 and 48 receiving mRNA-1273) were included (median age 41 years; 66-78% female). Nucleocapsid IgG was found in 4.1% and 21.9% of the BNT162b2 (baseline) and mRNA-1273 (2-weeks post first dose). All anti-spike assays detected antibodies post-vaccination, with an average increase of 87.2% (range 73.8-94.3%; BNT162b2), and 25.2% (range 23.8-26.7%; mRNA-1273) between the first and last sampling time points (all p < 0.05). Neutralizing antibodies were detected at all post-vaccine timepoints for both vaccine arms, with increasing titers over time (all p < 0.05). CONCLUSIONS: Anti-spike vaccine-induced SARS-CoV-2 IgG are detectable by commercially available high-throughput assays and increases over time. Prior to second dose of vaccination, neutralizing antibodies are detectable in 73-89% of individuals, suggesting most individuals would have some degree of protection from subsequent infection.

Age still matters: prognosticating short- and long-term mortality for critically ill patients with pneumonia.

OBJECTIVE: To determine the association between age and mortality in critically ill patients with pneumonia. We hypothesized that increasing age would be independently associated with both short- and long-term mortality. DESIGN: Prospective population-based cohort study examining the association between age and 30-day (short-term) and 1-yr (long-term) mortality using Cox proportional hazards regression, adjusting for pneumonia severity, mechanical ventilation, sex, functional status, nursing home residence, and having a living will. SETTING: Five intensive care units in Edmonton, Alberta, Canada. PATIENTS: Critically ill adult patients with pneumonia. MEASUREMENTS AND MAIN RESULTS: The cohort included 351 intensive care unit patients; mean age 61 yrs, 59% male, 16% from nursing homes. Mean Pneumonia Severity Index was 115 (73% Pneumonia Severity Index class IV or V), mean Acute Physiology and Chronic Health Evaluation II score 17, and 83% received invasive mechanical ventilation. Overall, 151 (43%) were < 60 yrs old, 64 (18%) were 60-69 yrs old, 82 (23%) were 70-79 yrs old, and 54 (15%) were ≥ 80 yrs old. By 30 days, 58 of 351 (17%) had died; by 1 yr, 112 of 351 (32%) had died. Mortality increased with age, 28 of 151 (19%) in those < 60 yrs, 14 of 64 (22%) in those 60-69 yrs, 39 of 82 (48%) in those 70-79 yrs, and 31 of 54 (57%) in those ≥ 80 yrs. Independent of pneumonia severity and other factors, age (per 10-yr increase) was associated with 30-day mortality (adjusted hazard ratio 1.24, 95% confidence interval 1.03-1.49, p = .026) and 1-yr mortality (adjusted hazard ratio 1.39, 95% confidence interval 1.21-1.60, p < .001). Having a living will was similarly associated with increased mortality (adjusted hazard ratio 3.08, 95% confidence interval 1.61-5.90, p < .001 at 30 days; adjusted hazard ratio 2.00, 95% confidence interval 1.21-3.32, p = .007 at 1 yr). CONCLUSIONS: Increasing age was independently associated with risk-adjusted short- and long-term mortality in critically ill patients with pneumonia. These findings may help elderly patients, their families, and physicians better understand what intensive care unit admission can offer and help them to make more informed decisions.

Pseudomonas aeruginosa infection in intensive care: Epidemiology, outcomes, and antimicrobial susceptibilities.

Background: Pseudomonas aeruginosa (PA) infection in the intensive care unit (ICU) contributes to substantial mortality. In this study, we describe the epidemiology, antimicrobial susceptibilities, and outcomes of ICU patients with pseudomonal infection. Methods: ICU patients with PA were identified and classified as colonized or infected. Infected patients were reviewed for source, patient characteristics, antimicrobial susceptibilities, appropriateness of empiric antimicrobial therapy, and 30-day mortality. Independent predictors of mortality were identified using multivariable logistic regression. Results: One hundred forty (71%) patients with PA were infected. Mean patient age was 55 (SD 18) years; 62% were male. Admission categories included medical (71%), surgical (20%), and trauma or neurological (9%). Mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 19 (SD 10). One hundred twenty-six (90%) patients were mechanically ventilated, 102 (73%) required vasopressors, and 27 (19%) received renal replacement; 32 (23%) died within 30 days. Infection was nosocomial in 101 (72%) cases. Sources were respiratory (66%), skin-soft tissue (11%), urinary (10%), blood (5%), surgical (5%), gastrointestinal (2%), or unknown (1%). Twenty (14%) isolates were multi-drug resistant; 6 (4%) were extensively drug resistant. Empiric antimicrobial therapy was effective in 97 (69%) cases. Liver disease (adjusted OR [aOR] 6.2, 95% CI 1.5 to 25.7; p = 0.01), malignancy (aOR 5.0, 95% CI 1.5 to 17.3; p = 0.01), and higher APACHE II score (aOR 1.1, 95% CI 1.0 to 1.1; p = 0.02) were independently associated with 30-day mortality. Conclusions: PA infection in ICU is most commonly respiratory and associated with substantial mortality. Existing malignancy, liver disease, and higher APACHE II score were independently associated with mortality.

Historique: L'infection à Pseudomonas aeruginosa (PA) contribue à une mortalité importante en soins intensifs. Dans la présente étude, les chercheurs décrivent l'épidémiologie, les susceptibilités antimicrobiennes et les résultats cliniques des patients atteints d'une infection à Pseudomonas hospitalisés en soins intensifs. Méthodologie: Les chercheurs ont répertorié les patients en soins intensifs atteints d'un PA et les ont classés comme colonisés ou infectés. Ils ont revu les dossiers des patients infectés pour connaître la source de l'infection, les caractéristiques des patients, leurs susceptibilités antimicrobiennes, le bien-fondé d'un traitement antimicrobien empirique et la mortalité au bout de 30 jours. Ils ont déterminé les prédicteurs indépendants de la mortalité au moyen de la régression logistique multivariable. Résultats: Cent quarante patients atteints d'un PA (71 %) étaient infectés. Ils avaient un âge moyen de 55 ans (ÉT 18), et 62 % étaient de sexe masculin. Les hospitalisations étaient d'ordre médical (71 %), chirurgical (20 %) et traumatique-neurologique (9 %). Le score APACHE II (Acute Physiology and Chronic Health Evaluation ou évaluation de la physiologie aiguë et de la santé chronique) s'élevait à 19 (ÉT 10). Cent vingt-six patients (90 %) étaient sous ventilation mécanique, 102 (73 %) dépendaient des vasopresseurs, 27 (19 %) ont reçu une transplantation rénale et 32 (23 %) sont décédés dans les 30 jours. Dans 101 cas (72 %), l'infection était d'origine nosocomiale. L'infection était de source respiratoire (66 %), cutanée-tissus mous (11 %), urinaire (10 %), sanguine (5 %), chirurgicale (5 %), gastro-intestinale (2 %) ou inconnue (1 %). Vingt isolats (14 %) étaient multirésistants et six (4 %), ultrarésistants. Le traitement antimicrobien empirique a été efficace dans 97 cas (69 %). Une maladie hépatique (rapport de cotes corrigé [RCc] 6,2, IC À 95 %, 1,5 à 25,7; p = 0,01), une tumeur maligne (RCc 5,0, IC à 95 %, 1,5 à 17,3; p = 0,01) et un score APACHE II élevé (RCc 1,1, IC à 95 %, 1,0 à 1,1; p = 0,02) étaient liés de façon indépendante à la mortalité au bout de 30 jours. Conclusions: L'infection à PA en soins intensifs est surtout de source respiratoire et associée à une mortalité importante. La préexistence d'une tumeur maligne, d'une maladie hépatique et d'un score APACHE II élevé était liée de façon indépendante à la mortalité.

Safety and efficacy of corticosteroids for the treatment of septic shock: A systematic review and meta-analysis.

BACKGROUND: Septic shock is common and results in significant morbidity and mortality. Adjunctive treatment with corticosteroids is common, but definitive data are lacking. We aimed to determine the efficacy and safety of corticosteroid therapy among patients with septic shock. METHODS: Medline, Embase, Cochrane Library, Web of Science, and Google Scholar were searched for randomized trials and observational studies published from January 1993 through December 2008. Studies were selected if they included adults with septic shock, discussed treatment with intravenous corticosteroids, and reported at least 1 outcome of interest (e.g., mortality, shock reversal, or incidence of superinfection). Two reviewers independently agreed on eligibility, assessed methodologic quality, and abstracted data. RESULTS: Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated for 28-day all-cause mortality, shock reversal at 7 days, and incidence of superinfection with use of random-effects models. Analyses, stratified by adrenal responsiveness, were prespecified. Eight studies (6 randomized trials) involving a total of 1876 patients were selected. Overall, corticosteroid therapy did not result in a statistically significant difference in mortality (42.2% [369 of 875 patients] vs. 38.4% [384 of 1001]; RR, 1.00; 95% CI, 0.84-1.18). A statistically significant difference in the incidence of shock reversal at 7 days was observed between patients who received corticosteroids and those who did not (64.9% [314 of 484 patients] vs. 47.5% [228 of 480]; RR, 1.41; 95% CI, 1.22-1.64), with similar point estimates for both corticotropin stimulation test responders and nonresponders. No statistically significant difference was found in the incidence of superinfection between patients treated with corticosteroids and patients not treated with corticosteroids (25.3% [114 of 450 patients] vs. 22.7% [100 of 441]; RR, 1.11; 95% CI, 0.86-1.42). CONCLUSIONS: In patients with septic shock, corticosteroid therapy appears to be safe but does not reduce 28-day all-cause mortality rates. It does, however, significantly reduce the incidence of vasopressor-dependent shock, which may be a clinically worthwhile goal.