Microbial aetiology of community-acquired pneumonia in hospitalized adults: a prospective study utilising comprehensive molecular testing.

OBJECTIVES: This study aimed to describe the microbial aetiology of community-acquired pneumonia (CAP) in adults admitted to a tertiary care hospital and assess the impact of syndromic polymerase chain reaction (PCR) panels on pathogen detection. METHODS: Conducted at Haukeland University Hospital, Norway, from September 2020 to April 2023, this prospective study enrolled adults with suspected CAP. We analyzed lower respiratory tract samples using both standard-of-care tests and the BIOFIRE® FILMARRAY® Pneumonia Plus Panel (FAP plus). The added value of FAP Plus in enhancing the detection of clinically relevant pathogens, alongside standard-of-care diagnostics, was assessed. RESULTS: Of the 3,238 patients screened, 640 met the inclusion criteria, with 384 confirmed to have CAP at discharge. In these patients, pathogens with proven or probable clinical significance were identified in 312 (81.3%) patients. Haemophilus influenzae was the most prevalent pathogen, found in 118 patients (30.7%), followed by SARS-CoV-2 in 74 (19.3%), and Streptococcus pneumoniae in 64 (16.7%). Respiratory viruses were detected in 186 (48.4%) patients. The use of FAP plus improved the pathogen detection rate from 62.8% with standard-of-care methods to 81.3%. CONCLUSIONS: Pathogens were identified in 81% of CAP patients, with Haemophilus influenzae and respiratory viruses being the most frequently detected pathogens. The addition of the FAP plus panel, markedly improved pathogen detection rates compared to standard of care diagnostics alone.

Diagnostic Stewardship in Community-Acquired Pneumonia With Syndromic Molecular Testing: A Randomized Clinical Trial.

Importance: Lower respiratory tract (LRT) infections, including community-acquired pneumonia (CAP), are a leading cause of hospital admissions and mortality. Molecular tests have the potential to optimize treatment decisions and management of CAP, but limited evidence exists to support their routine use. Objective: To determine whether the judicious use of a syndromic polymerase chain reaction (PCR)-based panel for rapid testing of CAP in the emergency department (ED) leads to faster, more accurate microbiological test result-based treatment. Design, Setting, and Participants: This parallel-arm, single-blinded, single-center, randomized clinical superiority trial was conducted between September 25, 2020, and June 21, 2022, in the ED of Haukeland University Hospital, a large tertiary care hospital in Bergen, Norway. Adult patients who presented to the ED with suspected CAP were recruited. Participants were randomized 1:1 to either the intervention arm or standard-of-care arm. The primary outcomes were analyzed according to the intention-to-treat principle. Intervention: Patients randomized to the intervention arm received rapid syndromic PCR testing (BioFire FilmArray Pneumonia plus Panel; bioMérieux) of LRT samples and standard of care. Patients randomized to the standard-of-care arm received standard microbiological diagnostics alone. Main Outcomes and Measures: The 2 primary outcomes were the provision of pathogen-directed treatment based on a microbiological test result and the time to provision of pathogen-directed treatment (within 48 hours after randomization). Results: There were 374 patients (221 males [59.1%]; median (IQR) age, 72 [60-79] years) included in the trial, with 187 in each treatment arm. Analysis of primary outcomes showed that 66 patients (35.3%) in the intervention arm and 25 (13.4%) in the standard-of-care arm received pathogen-directed treatment, corresponding to a reduction in absolute risk of 21.9 (95% CI, 13.5-30.3) percentage points and an odds ratio for the intervention arm of 3.53 (95% CI, 2.13-6.02; P < .001). The median (IQR) time to provision of pathogen-directed treatment within 48 hours was 34.5 (31.6-37.3) hours in the intervention arm and 43.8 (42.0-45.6) hours in the standard-of-care arm (mean difference, -9.4 hours; 95% CI, -12.7 to -6.0 hours; P < .001). The corresponding hazard ratio for intervention compared with standard of care was 3.08 (95% CI, 1.95-4.89). Findings remained significant after adjustment for season. Conclusions and Relevance: Results of this randomized clinical trial indicated that routine deployment of PCR testing for LRT pathogens led to faster and more targeted microbial treatment for patients with suspected CAP. Rapid molecular testing could complement or replace selected standard, time-consuming, laboratory-based diagnostics. Trial Registration: ClinicalTrials.gov Identifier: NCT04660084.

Epstein-Barr in a Patient Presenting with Right Upper Quadrant Pain: A Case Report from the Emergency Department.

BACKGROUND: Right upper quadrant abdominal pain and elevated cholestasis blood tests are usually associated with bacterial calculous cholecystitis. However, viral infections, such as Epstein-Barr virus (EBV) can also manifest with a similar clinical picture and is an important differential diagnosis. CASE REPORT: This case report discusses a young woman presenting to the emergency department with acute right upper quadrant abdominal pain. The initial assessment revealed a positive Murphy's sign, elevated white blood count, and a cholestatic pattern on liver function tests, leading one to suspect bacterial calculous cholecystitis and initiating antibiotic therapy. However, clinical examination also revealed tonsillar exudates and differential white blood cell count revealed monocytosis and lymphocytosis rather than a high neutrophil count. The patient tested positive for EBV. Furthermore, ultrasound and magnetic resonance imaging revealed gallbladder wall edema with no gallstones, leading one to conclude that the clinical manifestation and laboratory results were due to an EBV infection. Antibiotic therapy was ceased and the patient did not require surgical intervention. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Calculous bacterial cholecystitis usually entails antibiotic therapy and cholecystectomy. It is important to be aware of the differential diagnosis of EBV, as it usually does not require either of these and resolves spontaneously.

Use of corticosteroids in Norwegian patients with immunoglobulin a nephropathy progressing to end-stage kidney disease: a retrospective cohort study.

BACKGROUND: Despite several clinical trials, the use of corticosteroid therapy for treating immunoglobulin A nephropathy (IgAN) remains controversial. We aimed to describe the use of corticosteroid therapy combined with supportive therapy in Norwegian patients with IgAN who had progressed to end-stage kidney disease. METHODS: We conducted a retrospective cohort study using data from the Norwegian Renal Registry. Overall, 143 patients with primary IgAN who progressed to end-stage kidney disease were divided into two groups: the corticosteroid group, who had been treated with corticosteroids and supportive therapy, and the non-corticosteroid group, which had underwent only supportive therapy. The kidney function, time to end-stage kidney disease, and adverse effects were described. The observation period lasted from the diagnostic kidney biopsy until the initiation of kidney replacement therapy. RESULTS: Of the 143 included patients, 103 underwent supportive therapy alone, and 40 were treated with corticosteroids. Most patients (94%) were treated with renin-angiotensin-system blockade, and all patients reached end-stage kidney disease after a median of 5 years (interquartile range; 2-9 years). Time from diagnosis until end-stage kidney disease was similar in the two study groups (p = 0.98). During 6 months of corticosteroid therapy, median eGFR declined from 21 (interquartile range; 13-46) mL/min/1.73 m2 to 20 (interquartile range; 12-40) mL/min/1.73 m2, and median proteinuria decreased from 5.5 g/24 h to 3.0 g/24 h. Most patients (87.5%) treated with corticosteroids reported adverse events. In our linear regression analysis investigating the time to ESKD, we found that age (ß = -0.079, p = 0.008) and proteinuria at diagnosis (ß = -0.50, p = 0.01) exhibited statistically significant associations with a delay in the progression to ESKD. CONCLUSIONS: In this cohort of Norwegian patients with IgAN, corticosteroid therapy did not affect the time from diagnosis until end-stage kidney disease among a cohort of patients who all reached end-stage kidney disease. The treatment was also associated with adverse effects.

Prognostic significance of chronic myocardial injury diagnosed by three different cardiac troponin assays in patients admitted with suspected acute coronary syndrome.

OBJECTIVES: Chronic myocardial injury (CMI) is defined as stable concentrations of cardiac troponin T or I (cTnT or cTnI) above the assay-specific 99th percentile upper reference limit (URL) and signals poor outcome. The clinical implications of diagnosing CMI are unclear. We aimed to assess prevalence and association of CMI with long-term prognosis using three different high-sensitivity cTn (hs-cTn) assays. METHODS: A total of 1,292 hospitalized patients without acute myocardial injury had cTn concentrations quantified by hs-cTn assays by Roche Diagnostics, Abbott Diagnostics and Siemens Healthineers. The median follow-up time was 4.1 years. The prevalence of CMI and hazard ratios for mortality and cardiovascular (CV) events were calculated based on the URL provided by the manufacturers and compared to the prognostic accuracy when lower percentiles of cTn (97.5, 95 or 90), limit of detection or the estimated bioequivalent concentrations between assays were used as cutoff values. RESULTS: There was no major difference in prognostic accuracy between cTnT and cTnI analyzed as continuous variables. The correlation between cTnT and cTnI was high (r=0.724-0.785), but the cTnT assay diagnosed 3.9-4.5 times more patients with having CMI based on the sex-specific URLs (TnT, n=207; TnI Abbott, n=46, TnI Siemens, n=53) and had higher clinical sensitivity and AUC at the URL. CONCLUSIONS: The prevalence of CMI is highly assay-dependent. cTnT and cTnI have similar prognostic accuracy for mortality or CV events when measured as continuous variables. However, a CMI diagnosis according to cTnT has higher prognostic accuracy compared to a CMI diagnosis according to cTnI.

Glomerular transcriptomics predicts long term outcome and identifies therapeutic strategies for patients with assumed benign IgA nephropathy.

Some patients diagnosed with benign IgA nephropathy (IgAN) develop a progressive clinical course, not predictable by known clinical or histopathological parameters. To assess if gene expression can differentiate between progressors and non-progressors with assumed benign IgAN, we tested microdissected glomeruli from archival kidney biopsy sections from adult patients with stable clinical remission (21 non-progressors) or from 15 patients that had undergone clinical progression within a 25-year time frame. Based on 1 240 differentially expressed genes from patients with suitable sequencing results, we identified eight IgAN progressor and nine non-progressor genes using a two-component classifier. These genes, including APOL5 and ZXDC, predicted disease progression with 88% accuracy, 75% sensitivity and 100% specificity on average 21.6 years before progressive disease was clinically documented. APOL lipoproteins are associated with inflammation, autophagy and kidney disease while ZXDC is a zinc-finger transcription factor modulating adaptive immunity. Ten genes from our transcriptomics data overlapped with an external genome wide association study dataset, although the gene set enrichment test was not statistically significant. We also identified 45 drug targets in the DrugBank database, including angiotensinogen, a target of sparsentan (dual antagonist of the endothelin type A receptor and the angiotensin II type 1 receptor) currently investigated for IgAN treatment. Two validation cohorts were used for substantiating key results, one by immunohistochemistry and the other by nCounter technology. Thus, glomerular mRNA sequencing from diagnostic kidney biopsies from patients with assumed benign IgAN can differentiate between future progressors and non-progressors at the time of diagnosis.

Long-term follow-up of IgA nephropathy: clinicopathological features and predictors of outcomes.

Background: The establishment of the Oxford classification and newly developed prediction models have improved the prognostic information for immunoglobulin A nephropathy (IgAN). Considering new treatment options, optimizing prognostic information and improving existing prediction models are favorable. Methods: We used random forest survival analysis to select possible predictors of end-stage kidney disease among 37 candidate variables in a cohort of 232 patients with biopsy-proven IgAN retrieved from the Norwegian Kidney Biopsy Registry. The predictive value of variables with relative importance >5% was assessed using concordance statistics and the Akaike information criterion. Pearson's correlation coefficient was used to identify correlations between the selected variables. Results: The median follow-up period was 13.7 years. An isolated analysis of histological variables identified six variables with relative importance >5%: T %, segmental glomerular sclerosis without characteristics associated with other subtypes (not otherwise specified, NOS), normal glomeruli, global sclerotic glomeruli, segmental adherence and perihilar glomerular sclerosis. When histopathological and clinical variables were combined, estimated glomerular filtration rate (eGFR), proteinuria and serum albumin were added to the list. T % showed a better prognostic value than tubular atrophy/interstitial fibrosis (T) lesions with C-indices at 0.74 and 0.67 and was highly correlated with eGFR. Analysis of the subtypes of segmental glomerulosclerosis (S) lesions revealed that NOS and perihilar glomerular sclerosis were associated with adverse outcomes. Conclusions: Reporting T lesions as a continuous variable, normal glomeruli and subtypes of S lesions could provide clinicians with additional prognostic information and contribute to the improved performance of the Oxford classification and prognostic tools.

Prognostic value of growth differentiation factor-15 3 months after an acute chest pain admission.

OBJECTIVE: Growth differentiation factor-15 (GDF-15) is a predictor of death and cardiovascular events when measured during index hospitalisation in patients with acute chest pain. This study investigated the prognostic utility of measuring GDF-15 3 months after an admission with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: GDF-15 was measured at baseline and 3 months after admission in 758 patients admitted with suspected NSTE-ACS. Patients were followed for a median of 1540 (IQR: 1087-1776) days after the 3-month visit. The primary endpoint was all-cause mortality, while the secondary composite endpoint included all-cause mortality, incident myocardial infarction and heart failure hospitalisation during follow-up. RESULTS: In patients with GDF-15 ≥1200 pg/mL (n=248), 18% died and 25% met the composite endpoint. In patients with GDF-15 <1200 pg/mL (n=510), 1.7% died and 4% met the composite endpoint. The GDF-15 concentration (log2 transformed) at 3 months was significantly associated with all-cause mortality (adjusted HR: 2.2, 95% CI: 1.4 to 3.3, p<0.001) and the composite endpoint (adjusted HR: 1.9, 95% CI: 1.4 to 2.7, p<0.001), independently of traditional risk factors and baseline troponin T. A 10% change in GDF-15 concentration from baseline to the 3-month visit was associated with increased risk of all-cause mortality (HR: 1.06, 95% CI: 1.01 to 1.13, p=0.031), adjusting for baseline GDF-15 concentrations. CONCLUSIONS: High GDF-15 concentrations 3 months after admission for suspected NSTE-ACS are associated with long-term mortality and cardiovascular events, independent of traditional risk factors and troponin T. A change in GDF-15 concentration can provide prognostic information.

Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain using Point of Care Testing (WESTCOR-POC): study design.

OBJECTIVES: Patients presenting with symptoms suggestive of acute coronary syndrome (ACS) contribute to a high workload and overcrowding in the Emergency Department (ED). Accelerated diagnostic protocols for non-ST-elevation myocardial infarction have proved challenging to implement. One obstacle is the turnaround time for analyzing high-sensitivity cardiac troponin (hs-cTn). In the WESTCOR-POC study (Clinical Trials number NCT05354804) we aim to evaluate safety and efficiency of a 0/1 h hs-cTn algorithm utilizing a hs-cTnI point of care (POC) instrument in comparison to central laboratory hs-cTnT measurements. DESIGN: This is a prospective single-center randomized clinical trial aiming to include 1500 patients admitted to the ED with symptoms suggestive of ACS. Patients will receive standard investigations following the European Society of Cardiology 0/1h protocols for centralized hs-cTnT measurements or the intervention using a 0/1h POC hs-cTnI algorithm. Primary end-points are 1) Safety; death, myocardial infarction or acute revascularization within 30 days 2) Efficiency; length of stay in the ED, 3) Cost- effectiveness; total episode cost, 4) Patient satisfaction, 5) Patient symptom burden and 6) Patients quality of life. Secondary outcomes are 12-months death, myocardial infarction or acute revascularization, percentage discharged after 3 and 6 h, total length of hospital stay and all costs related to hospital contact within 12 months. CONCLUSION: Results from this study may facilitate implementation of POC hs-cTn testing assays and accelerated diagnostic protocols in EDs, and may serve as a valuable resource for guiding future investigations for the use of POC high sensitivity troponin assays in outpatient clinics and prehospital settings.

The diagnostic utility of microscopic quality assessment of sputum samples in the era of rapid syndromic PCR testing.

This prospective study assessed the value of initial microscopy evaluation of sputum samples submitted for rapid syndromic PCR-based testing. Bacterial detections by the BioFire FilmArray Pneumonia Panel plus in 126 high- and 108 low-quality sputum samples, based on initial microscopy evaluation in samples from patients with lower respiratory tract infections were compared. We found that high-quality samples had a higher proportion of bacterial detections compared to low-quality samples (P = 0.013). This included a higher proportion of detections of bacteria deemed clinically relevant by predefined criteria (70% and 55%, P = 0.016), as well as a higher proportion of detections of Haemophilus influenzae (36% and 20%, P = 0.010). High-quality samples also had more detections of bacteria with high semi-quantitative values. The study found no significant difference between high- and low-quality samples in the proportions of samples with a single species of bacteria detected, samples with a bacteria treated by the clinician, samples with detection of a proven etiology of community-acquired pneumonia by predefined criteria, the number of bacterial species detected, or the detection of Streptococcus pneumoniae, Moraxella catarrhalis, or Staphylococcus aureus. The results showed that 40% (95% CI 35%-47%) of the bacterial detections would have been missed if only high-quality samples were analyzed. This included 41% (27%-56%) of detections of S. pneumoniae, 33% (23%-45%) of detections of H. influenzae, 42% (28%-58%) of detections of S. aureus, and 37% (23%-54%) of detections of M. catarrhalis. These findings suggest that all sputum samples submitted for rapid syndromic PCR testing should be analyzed, regardless of initial microscopy quality assessment. (This study has been registered at ClinicalTrials.gov under registration no. NCT04660084.) IMPORTANCE Microscopic quality assessment of sputum samples was originally designed for sputum culture, and its applicability in today's workflow, which includes syndromic PCR testing, may differ. Addressing this crucial gap, our study emphasizes the need to optimize the use and workflow of syndromic PCR panels, like the BioFire FilmArray Pneumonia plus (FAP plus), in microbiology laboratories. These advanced PCR-based tests offer rapid and comprehensive pathogen detection for respiratory infections, yet their full potential remains uncertain. By comparing bacterial detections in high- and low-quality sputum samples, we underscore the importance of including low-quality samples in testing. Our findings reveal a significant proportion of potentially clinically relevant bacterial detections that would have been missed if only high-quality samples were analyzed. These insights support the efficient implementation of syndromic PCR panels, ultimately enhancing patient care and outcomes.

Diagnostic utility of oropharyngeal swabs as an alternative to lower respiratory tract samples for PCR-based syndromic testing in patients with community-acquired pneumonia.

Syndromic PCR-based analysis of lower respiratory tract (LRT) samples in patients with community-acquired pneumonia (CAP) improves the bacterial yield and time-to-results compared to culture-based methods. However, obtaining adequate sputum samples can be challenging and is frequently not prioritized in the emergency department (ED). In this study, we assess the concordance of microbiological detections between oropharyngeal- (OP) and LRT samples from patients presenting to the ED with CAP using a syndromic PCR-based respiratory panel [Biofire FilmArray Pneumonia plus (FAP plus)]. Paired OP- and high-quality LRT samples were collected from 103 patients with confirmed CAP, who had been included in a randomized controlled trial (NCT04660084) or a subsequent observational study at Haukeland University Hospital, and analyzed using the FAP plus. The LRT samples were obtained mainly by sputum induction (88%). Using the LRT samples as a reference standard, the positive percent agreement (PPA), negative percent agreement (NPA), and overall percent agreement for the most common bacterial pathogens in CAP, Streptococcus pneumoniae and Haemophilus influenzae, were 85%, 99% and 95%, and 86%, 98% and 93%, respectively. For Moraxella catarrhalis, the PPA was lower (74%), while the NPA was 100%. For bacteria that are less likely causes of uncomplicated CAP (e.g., Staphylococcus aureus and Enterobacterales) the results were more divergent. In conclusion, the FAP plus detects the most common CAP pathogens S. pneumoniae and H. influenzae from OP samples with high PPAs and excellent NPAs when compared with LRT samples. For these pathogens, the PPAs for OP samples were higher than previous reports for nasopharyngeal samples. This suggests that analysis of OP samples with syndromic PCR panels could represent an alternative approach for rapid microbiological testing in the ED, especially in patients where LRT samples are difficult to obtain. Divergent results for bacteria that are less likely to cause uncomplicated CAP do, however, emphasize the need for clinical evaluation of positive test results.

Validation of a modified South African triage scale in a high-resource setting: a retrospective cohort study.

BACKGROUND: Triage systems are widely used in emergency departments, but are not always validated. The South African Triage Scale (SATS) has mainly been studied in resource-limited settings. The aim of this study was to determine the validity of a modified version of the SATS for the general population of patients admitted to an ED at a tertiary hospital in a high-income country. The secondary objective was to study the triage performance according to age and patient categories. METHODS: We conducted a retrospective cohort study of patients presenting to the Emergency Department of Haukeland University Hospital in Norway during a four-year period. We used short-term mortality, ICU admission, and the need for immediate surgery and other interventions as the primary endpoints. RESULTS: A total of 162,034 emergency department visits were included in the analysis. The negative predictive value of a low triage level to exclude severe illness was 99.1% (95% confidence interval: 99.0-99.2%). The level of overtriage, defined as the proportion of patients assigned to a high triage level who were not admitted to the hospital, was 4.1% (3.9-4.2%). Receiver operating characteristic (ROC) curves showed an area under the ROC for the detection of severe illness of 0.874 (95% confidence interval: 0.870-0.879) for all patients and 0.856 (0.837-0.875), 0.884 (0.878-0.890) and 0.869 (0.862-0.876) for children, adults and elderly individuals respectively. CONCLUSION: We found that the modified SATS had a good sensitivity to identify short-term mortality, ICU admission, and the need for rapid surgery and other interventions. The sensitivity was higher in adults than in children and higher in medical patients than in surgical patients. The over- and undertriage rates were acceptable.

Growth Differentiation Factor 15: A Prognostic Marker in Patients with Acute Chest Pain without Acute Myocardial Infarction.

BACKGROUND: Acute chest pain is associated with an increased risk of death and cardiovascular events even when acute myocardial infarction (AMI) has been excluded. Growth differentiation factor-15 (GDF-15) is a strong prognostic marker in patients with acute chest pain and AMI, but the prognostic value in patients without AMI is uncertain. This study sought to investigate the ability of GDF-15 to predict long-term prognosis in patients presenting with acute chest pain without AMI. METHODS: In total, 1320 patients admitted with acute chest pain without AMI were followed for a median of 1523 days (range: 4 to 2208 days). The primary end point was all-cause mortality. Secondary end points included cardiovascular (CV) death, future AMI, heart failure hospitalization, and new-onset atrial fibrillation (AF). RESULTS: Higher concentrations of GDF-15 were associated with increased risk of death from all causes (median concentration in non-survivors vs survivors: 2124 pg/mL vs 852 pg/mL, P < 0.001), and all secondary end points. By multivariable Cox regression, GDF-15 concentration ≥4th quartile (compared to <4th quartile) remained an independent predictor of all-cause death (adjusted hazard ratio (HR): 2.75; 95% CI, 1.69-4.45, P < 0.001), CV death (adjusted HR: 3.74; 95% CI, 1.31-10.63, P = 0.013), and heart failure hospitalization (adjusted HR: 2.60; 95% CI, 1.11-6.06, P = 0.027). Adding GDF-15 to a model consisting of established risk factors and high-sensitivity cardiac troponin T (hs-cTnT) led to a significant increase in C-statistics for prediction of all-cause mortality. CONCLUSIONS: Higher concentrations of GDF-15 were associated with increased risk of mortality from all causes and risk of future CV events.

Validation of two IgA nephropathy risk-prediction tools using a cohort with a long follow-up.

BACKGROUND: Recently, two immunoglobulin A (IgA) nephropathy-prediction tools were developed that combine clinical and histopathologic parameters. The International IgAN Prediction Tool predicts the risk for 50% declines in the estimated glomerular filtration rate or end-stage kidney disease up to 80 months after diagnosis. The IgA Nephropathy Clinical Decision Support System uses artificial neural networks to estimate the risk for end-stage kidney disease. We aimed to externally validate both prediction tools using a Norwegian cohort with a long-term follow-up. METHODS: We included 306 patients with biopsy-proven primary IgA nephropathy in this study. Histopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry and reclassified according to the Oxford Classification. We used discrimination and calibration as principles for externally validating the prognostic models. RESULTS: The median patient follow-up was 17.1 years. A cumulative, dynamic, time-dependent receiver operating characteristic analysis showed area under the curve values ranging from 0.90 at 5 years to 0.83 at 20 years for the International IgAN Prediction Tool, while time-naive analysis showed an area under the curve value at 0.83 for the IgA Nephropathy Clinical Decision Support System. The International IgAN Prediction Tool was well calibrated, while the IgA Nephropathy Clinical Decision Support System tends to underestimate risk for patients at higher risk and overestimates risk in the lower risk categories. CONCLUSIONS: We have externally validated two prediction tools for IgA nephropathy. The International IgAN Prediction Tool performed well, while the IgA Nephropathy Clinical Decision Support System has some limitations.

The changing spectrum of microbial aetiology of respiratory tract infections in hospitalized patients before and during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic was met with strict containment measures. We hypothesized that societal infection control measures would impact the number of hospital admissions for respiratory tract infections, as well as, the spectrum of pathogens detected in patients with suspected community acquired pneumonia (CAP). METHODS: This study is based on aggregated surveillance data from electronic health records of patients admitted to the hospitals in Bergen Hospital Trust from January 2017 through June 2021, as well as, two prospective studies of patients with suspected CAP conducted prior to and during the COVID-19 pandemic (pre-COVID cohort versus COVID cohort, respectively). In the prospective cohorts, microbiological detections were ascertained by comprehensive PCR-testing in lower respiratory tract specimens. Mann-Whitney's U test was used to analyse continuous variables. Fisher's exact test was used for analysing categorical data. The number of admissions before and during the outbreak of SARS-CoV-2 was compared using two-sample t-tests on logarithmic transformed values. RESULTS: Admissions for respiratory tract infections declined after the outbreak of SARS-CoV-2 (p < 0.001). The pre-COVID and the COVID cohorts comprised 96 and 80 patients, respectively. The proportion of viruses detected in the COVID cohort was significantly lower compared with the pre-COVID cohort [21% vs 36%, difference of 14%, 95% CI 4% to 26%; p = 0.012], and the proportion of bacterial- and viral co-detections was less than half in the COVID cohort compared with the pre-COVID cohort (19% vs 45%, difference of 26%, 95% CI 13% to 41%; p < 0.001). The proportion of bacteria detected was similar (p = 0.162), however, a difference in the bacterial spectrum was observed in the two cohorts. Haemophilus influenzae was the most frequent bacterial detection in both cohorts, followed by Streptococcus pneumoniae in the pre-COVID and Staphylococcus aureus in the COVID cohort. CONCLUSION: During the first year of the COVID-19 pandemic, the number of admissions with pneumonia and the microbiological detections in patients with suspected CAP, differed from the preceding year. This suggests that infection control measures related to COVID-19 restrictions have an overall and specific impact on respiratory tract infections, beyond reducing the spread of SARS-CoV-2.

Impact of rapid molecular testing on diagnosis, treatment and management of community-acquired pneumonia in Norway: a pragmatic randomised controlled trial (CAPNOR).

BACKGROUND: Community-acquired pneumonia (CAP) causes a large burden of disease. Due to difficulties in obtaining representative respiratory samples and insensitive standard microbiological methods, the microbiological aetiology of CAP is difficult to ascertain. With a few exceptions, standard-of-care diagnostics are too slow to influence initial decisions on antimicrobial therapy. The management of CAP is therefore largely based on empirical treatment guidelines. Empiric antimicrobial therapy is often initiated in the primary care setting, affecting diagnostic tests based on conventional bacterial culture in hospitalized patients. Implementing rapid molecular testing may improve both the proportion of positive tests and the time it takes to obtain test results. Both measures are important for initiation of pathogen-targeted antibiotics, involving rapid de-escalation or escalation of treatment, which may improve antimicrobial stewardship and potentially patient outcome. METHODS: Patients presenting to the emergency department of Haukeland University Hospital (HUH) in Bergen, Norway, will be screened for inclusion into a pragmatic randomised controlled trial (RCT). Eligible patients with a suspicion of CAP will be included and randomised to receive either standard-of-care methods (standard microbiological testing) or standard-of-care methods in addition to testing by the rapid and comprehensive real-time multiplex PCR panel, the BioFire® FilmArray® Pneumonia Panel plus (FAP plus) (bioMérieux S.A., Marcy-l'Etoile, France). The results of the FAP plus will be communicated directly to the treating staff within ~2 h of sampling. DISCUSSION: We will examine if rapid use of FAP plus panel in hospitalized patients with suspected CAP can improve both the time to and the proportion of patients receiving pathogen-directed treatment, thereby shortening the exposure to unnecessary antibiotics and the length of hospital admission, compared to the standard-of-care arm. The pragmatic design together with broad inclusion criteria and a straightforward intervention could make our results generalizable to other similar centres. TRIAL REGISTRATION: ClinicalTrials.gov NCT04660084 . Registered on December 9, 2020.

Predictors of long-term symptom burden and quality of life in patients hospitalised with chest pain: a prospective observational study.

OBJECTIVE: To describe the magnitude and predictors of symptom burden (SB) and quality of life (QoL) 3 months after hospital admission for acute chest pain. DESIGN: Prospective observational study. SETTING: Single centre, outpatient follow-up. PARTICIPANTS: 1506 patients. OUTCOMES: Scores reported for general health (RAND-12), angina-related health (Seattle Angina Questionnaire 7 (SAQ-7)) and dyspnoea (Rose Dyspnea Scale) 3 months after hospital admission for chest pain. METHODS: A total of 1506 patients received questionnaires assessing general health (RAND-12), angina-related health (SAQ-7) and dyspnoea (Rose Dyspnea Scale) 3 months after discharge. Univariable and multivariable regression models identified predictors of SB and QoL scores. A mediator analysis identified factors mediating the effect of an unstable angina pectoris (UAP) diagnosis. RESULTS: 774 (52%) responded. Discharge diagnoses were non-ST elevation myocardial infarction (NSTEMI) (14.2%), UAP (17.1%), non-coronary cardiac disease (6.6%), non-cardiac disease (6.3%) and non-cardiac chest pain (NCCP) (55.6%). NSTEMI had the most favourable, and UAP patients the least favourable SAQ-7 scores (median SAQ7-summary; 88 vs 75, p<0.001). NCCP patients reported persisting chest pain in 50% and dyspnoea in 33% of cases. After adjusting for confounders, revascularisation predicted better QoL scores, while UAP, current smoking and hypertension predicted worse outcome. NSTEMI and UAP patients who were revascularised reported higher scores (p<0.05) in SAQ-7-QL, SAQ7-PL, SAQ7-summary (NSTEMI) and all SAQ-7 domains (UAP). Revascularisation altered the unstandardised beta value (>±10%) of an UAP diagnosis for all SAQ-7 and RAND-12 outcomes. CONCLUSIONS: Patients with NSTEMI reported the most favourable outcome 3 months after hospitalisation for chest pain. Patients with other diseases, in particular UAP patients, reported lower scores. Revascularised NSTEMI and UAP patients reported higher QoL scores compared with patients receiving conservative treatment. Revascularisation mediated all outcomes in UAP patients. TRIAL REGISTRATION NUMBER: NCT02620202.

Association between symptoms and risk of non-ST segment elevation myocardial infarction according to age and sex in patients admitted to the emergency department with suspected acute coronary syndrome: a single-centre retrospective cohort study.

OBJECTIVES: Evaluate the association between symptoms and risk of non-ST segment elevation myocardial infarction (NSTEMI) in patients admitted to an emergency department with suspected acute coronary syndrome based on sex and age. DESIGN: Post hoc analysis of a prospective observational study conducted between September 2015 and May 2019. SETTING: University hospital in Norway. PARTICIPANTS: 1506 participants >18 years of age (39.6% women and 31.0% 70 years of age or older). FINDINGS: The OR for NSTEMI was 9.4 if pain radiated to both arms, 3.0 if exertional chest pain was present during the last week and 2.9 if pain occurred during activity. Men had significantly lower OR compared with women if pain was dependent of position, respiration or palpation (OR 0.17 vs 0.53, p value for interaction 0.047). Patients <70 years had higher predictive value than older patients if they reported exertional chest pain the last week (OR 4.08 vs 1.81, 95%, p value for interaction 0.025) and lower if pain radiated to the left arm (OR 0.73 vs 1.67, p value for interaction 0.045). CONCLUSIONS: Chest pain with radiation to both arms, exertional chest pain during the last week and pain during activity had the strongest predictive value for NSTEMI. The differences in symptom presentation and risk of NSTEMI between sex and age groups were small. TRIAL REGISTRATION NUMBER: WESTCOR study ClinicalTrials.gov (NCT02620202).

Implementing a new emergency medical triage tool in one health region in Norway: some lessons learned.

BACKGROUND: Acutely sick or injured patients depend on ambulance and emergency department personnel performing an accurate initial assessment and prioritisation (triage) to effectively identify patients in need of immediate treatment. Triage also ensures that each patient receives fair initial assessment. To improve the patient safety, quality of care, and communication about a patient's medical condition, we implemented a new triage tool (the South African Triage Scale Norway (SATS-N) in all the ambulance services and emergency departments in one health region in Norway. This article describes the lessons we learnt during this implementation process. METHODS: The main framework in this quality improvement (QI) work was the plan-do-study-act cycle. Additional process sources were 'The Institute for Healthcare Improvement Model for improvement' and the Norwegian Patient Safety Programme. RESULTS: Based on the QI process as a whole, we defined subjects influencing this work to be successful, such as identifying areas for improvement, establishing multidisciplinary teams, coaching, implementing measurements and securing sustainability. After these subjects were connected to the relevant challenges and desired effects, we described the lessons we learnt during this comprehensive QI process. CONCLUSION: We learnt the importance of following a structured framework for QI process during the implementation of the SATS-N triage tool. Furthermore, securing anchoring at all levels, from the managements to the medical professionals in direct patient-orientated work, was relevant important. Moreover, establishing multidisciplinary teams with ambulance personnel, emergency department nurses and doctors with various medical specialties provided ownership to the participants. Meanwhile, coaching provided necessary security for the staff directly involved in caring for patients. Keeping the spirit and perseverance high were important factors in completing the implementation. Establishment of the regional network group was found to be important for sustainability and further improvements.

Utilizing the MEST score for prognostic staging in IgA nephropathy.

BACKGROUND: The Oxford classification/MEST score is an established histopathologic scoring system for patients with IgA nephropathy (IgAN). The objective of this study was to derive a prognostic model for IgAN based on the MEST score and histopathologic features. METHODS: A total of 306 patients with biopsy-proven primary IgAN were included. Histopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry and reclassified according to the Oxford classification. The study endpoint was end-stage renal disease (ESRD). Patients were subclassified into three risk models based on histologic features (Model A), a composite score calculated from the adjusted hazard ratio values (Model B), and on quartiles (Model C). RESULTS: The mean follow-up time was 16.5 years (range 0.2-28.1). In total, 61 (20%) patients reached ESRD during the study period. Univariate analysis of M, E, S, T and C lesions demonstrated that all types were associated with an increased risk of ESRD; however, a multivariate analysis revealed that only S, T and C lesions were associated with poor outcomes. Statistical analysis of 15-year data demonstrated that Models A and B were as predictive as the MEST score, with an area-under-the-curve at 0.85. The Harrel c index values were 0.81 and 0.80 for the MEST score and Models A and B, respectively. In the present cohort, adding C lesions to the MEST score did not improve the models prognostic value. CONCLUSIONS: Patients can be divided into risk classes based on their MEST scores. Histopathologic data provide valuable prognostic information at the time of diagnosis. Model B was the most suitable for clinical practice because it was the most user-friendly.