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1.
  • Dave, Nishi, et al. (författare)
  • Nosocomial SARS-CoV-2 infections and mortality during unique COVID-19 epidemic waves
  • 2023
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Quantifying the burden of nosocomial SARS-CoV-2 infections and associated mortality is necessary to assess the need for infection prevention and control measures.Objective: To investigate the occurrence of nosocomial SARS-CoV-2 infections and associated 30-day mortality among patients admitted to hospitals in Region Stockholm, Sweden.Design, Setting, and Participants: A retrospective, matched cohort study divided the period from March 1, 2020, until September 15, 2022, into a prevaccination period, early vaccination and pre-Omicron (period 1), and late vaccination and Omicron (period 2). From among 303 898 patients 18 years or older living in Region Stockholm, 538 951 hospital admissions across all hospitals were included. Hospitalized admissions with nosocomial SARS-CoV-2 infections were matched to as many as 5 hospitalized admissions without nosocomial SARS-CoV-2 by age, sex, length of stay, admission time, and hospital unit.Exposure: Nosocomial SARS-CoV-2 infection defined as the first positive polymerase chain reaction test result at least 8 days after hospital admission or within 2 days after discharge.Main Outcomes and Measures: Primary outcome of 30-day mortality was analyzed using time-to-event analyses with a Cox proportional hazards regression model adjusted for age, sex, educational level, and comorbidities.Results: Among 2193 patients with SARS-CoV-2 infections or reinfections (1107 women [50.5%]; median age, 80 [IQR, 71-87] years), 2203 nosocomial SARS-CoV-2 infections were identified. The incidence rate of nosocomial SARS-CoV-2 infections was 1.57 (95% CI, 1.51-1.64) per 1000 patient-days. In the matched cohort, 1487 hospital admissions with nosocomial SARS-CoV-2 infections were matched to 5044 hospital admissions without nosocomial SARS-CoV-2 infections. Thirty-day mortality was higher in the prevaccination period (adjusted hazard ratio [AHR], 2.97 [95% CI, 2.50-3.53]) compared with period 1 (AHR, 2.08 [95% CI, 1.50-2.88]) or period 2 (AHR, 1.22 [95% CI, 0.92-1.60]). Among patients with nosocomial SARS-CoV-2 infections, 30-day AHR comparing those with 2 or more doses of SARS-CoV-2 vaccination and those with less than 2 doses was 0.64 (95% CI, 0.46-0.88).Conclusions and Relevance: In this matched cohort study, nosocomial SARS-CoV-2 infections were associated with higher 30-day mortality during the early phases of the pandemic and lower mortality during the Omicron variant wave and after the introduction of vaccinations. Mitigation of excess mortality risk from nosocomial transmission should be a strong focus when population immunity is low through implementation of adequate infection prevention and control measures.
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2.
  • Henriksson, Aron, 1985-, et al. (författare)
  • Multimodal fine-tuning of clinical language models for predicting COVID-19 outcomes
  • 2023
  • Ingår i: Artificial Intelligence in Medicine. - 0933-3657 .- 1873-2860. ; 146
  • Tidskriftsartikel (refereegranskat)abstract
    • Clinical prediction models tend only to incorporate structured healthcare data, ignoring information recorded in other data modalities, including free-text clinical notes. Here, we demonstrate how multimodal models that effectively leverage both structured and unstructured data can be developed for predicting COVID-19 outcomes. The models are trained end-to-end using a technique we refer to as multimodal fine-tuning, whereby a pre -trained language model is updated based on both structured and unstructured data. The multimodal models are trained and evaluated using a multicenter cohort of COVID-19 patients encompassing all encounters at the emergency department of six hospitals. Experimental results show that multimodal models, leveraging the notion of multimodal fine-tuning and trained to predict (i) 30-day mortality, (ii) safe discharge and (iii) readmission, outperform unimodal models trained using only structured or unstructured healthcare data on all three outcomes. Sensitivity analyses are performed to better understand how well the multimodal models perform on different patient groups, while an ablation study is conducted to investigate the impact of different types of clinical notes on model performance. We argue that multimodal models that make effective use of routinely collected healthcare data to predict COVID-19 outcomes may facilitate patient management and contribute to the effective use of limited healthcare resources.
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3.
  • Pawar, Yash, et al. (författare)
  • Leveraging Clinical BERT in Multimodal Mortality Prediction Models for COVID-19
  • 2022
  • Ingår i: In Proceedings of IEEE International Symposium on Computer-Based Medical Systems (CMBS 2022). - : IEEE. - 9781665467704 ; , s. 199-204
  • Konferensbidrag (refereegranskat)abstract
    • Clinical prediction models are often based solely on the use of structured data in electronic health records, e.g. vital parameters and laboratory results, effectively ignoring potentially valuable information recorded in other modalities, such as free-text clinical notes. Here, we report on the development of a multimodal model that combines structured and unstructured data. In particular, we study how best to make use of a clinical language model in a multimodal setup for predicting 30-day all-cause mortality upon hospital admission in patients with COVID-19. We evaluate three strategies for incorporating a domain-specific clinical BERT model in multimodal prediction systems: (i) without fine-tuning, (ii) with unimodal fine-tuning, and (iii) with multimodal fine-tuning. The best-performing model leverages multimodal fine-tuning, in which the clinical BERT model is updated based also on the structured data. This multimodal mortality prediction model is shown to outperform unimodal models that are based on using either only structured data or only unstructured data. The experimental results indicate that clinical prediction models can be improved by including data in other modalities and that multimodal fine-tuning of a clinical language model is an effective strategy for incorporating information from clinical notes in multimodal prediction systems.
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4.
  • Alam, Mahbub Ul, et al. (författare)
  • Deep Learning from Heterogeneous Sequences of Sparse Medical Data for Early Prediction of Sepsis
  • 2020
  • Ingår i: Proceedings of the 13th International Joint Conference on Biomedical Engineering Systems and Technologies, Volume 5: HEALTHINF. - Setúbal : SciTePress. - 9789897583988 ; , s. 45-55
  • Konferensbidrag (refereegranskat)abstract
    • Sepsis is a life-threatening complication to infections, and early treatment is key for survival. Symptoms of sepsis are difficult to recognize, but prediction models using data from electronic health records (EHRs) can facilitate early detection and intervention. Recently, deep learning architectures have been proposed for the early prediction of sepsis. However, most efforts rely on high-resolution data from intensive care units (ICUs). Prediction of sepsis in the non-ICU setting, where hospitalization periods vary greatly in length and data is more sparse, is not as well studied. It is also not clear how to learn effectively from longitudinal EHR data, which can be represented as a sequence of time windows. In this article, we evaluate the use of an LSTM network for early prediction of sepsis according to Sepsis-3 criteria in a general hospital population. An empirical investigation using six different time window sizes is conducted. The best model uses a two-hour window and assumes data is missing not at random, clearly outperforming scoring systems commonly used in healthcare today. It is concluded that the size of the time window has a considerable impact on predictive performance when learning from heterogeneous sequences of sparse medical data for early prediction of sepsis.
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5.
  • Alam, Mahbub Ul, et al. (författare)
  • Terminology Expansion with Prototype Embeddings : Extracting Symptoms of Urinary Tract Infection from Clinical Text
  • 2021
  • Ingår i: Proceedings of the 14th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2021) - Volume 5: HEALTHINF. - Setúbal : SciTePress. - 9789897584909 ; , s. 47-57
  • Konferensbidrag (refereegranskat)abstract
    • Many natural language processing applications rely on the availability of domain-specific terminologies containing synonyms. To that end, semi-automatic methods for extracting additional synonyms of a given concept from corpora are useful, especially in low-resource domains and noisy genres such as clinical text, where nonstandard language use and misspellings are prevalent. In this study, prototype embeddings based on seed words were used to create representations for (i) specific urinary tract infection (UTI) symptoms and (ii) UTI symptoms in general. Four word embedding methods and two phrase detection methods were evaluated using clinical data from Karolinska University Hospital. It is shown that prototype embeddings can effectively capture semantic information related to UTI symptoms. Using prototype embeddings for specific UTI symptoms led to the extraction of more symptom terms compared to using prototype embeddings for UTI symptoms in general. Overall, 142 additional UTI symp tom terms were identified, yielding a more than 100% increment compared to the initial seed set. The mean average precision across all UTI symptoms was 0.51, and as high as 0.86 for one specific UTI symptom. This study provides an effective and cost-effective solution to terminology expansion with small amounts of labeled data.
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6.
  • Alpkvist, Helena, et al. (författare)
  • Clinical and Microbiological Factors Associated with High Nasopharyngeal Pneumococcal Density in Patients with Pneumococcal Pneumonia
  • 2015
  • Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 10:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to study if certain clinical and/or microbiological factors are associated with a high nasopharyngeal (NP) density of Streptococcus pneumoniae in pneumococcal pneumonia. In addition, we aimed to study if a high NP pneumococcal density could be useful to detect severe pneumococcal pneumonia.Methods: Adult patients hospitalized for radiologically confirmed community-acquired pneumonia were included in a prospective study. NP aspirates were collected at admission and were subjected to quantitative PCR for pneumococcal DNA (Spn9802 DNA). Patients were considered to have pneumococcal etiology if S. pneumoniae was detected in blood culture and/ or culture of respiratory secretions and/or urinary antigen test.Results: Of 166 included patients, 68 patients had pneumococcal DNA detected in NP aspirate. Pneumococcal etiology was noted in 57 patients (84%) with positive and 8 patients (8.2%) with negative test for pneumococcal DNA (p<0.0001). The median NP pneumococcal density of DNA positive patients with pneumococcal etiology was 6.83 log(10) DNA copies/mL (range 1.79-9.50). In a multivariate analysis of patients with pneumococcal etiology, a high pneumococcal density was independently associated with severe pneumonia (Pneumonia Severity Index risk class IV-V), symptom duration >= 2 days prior to admission, and a medium/high serum immunoglobulin titer against the patient's own pneumococcal serotype. NP pneumococcal density was not associated with sex, age, smoking, co-morbidity, viral co-infection, pneumococcal serotype, or bacteremia. Severe pneumococcal pneumonia was noted in 28 study patients. When we studied the performance of PCR with different DNA cut-off levels for detection of severe pneumococcal pneumonia, we found sensitivities of 54-82% and positive predictive values of 37-56%, indicating suboptimal performance.Conclusions: Pneumonia severity, symptom duration similar to 2 days, and a medium/high serum immunoglobulin titer against the patient's own serotype were independently associated with a high NP pneumococcal density. NP pneumococcal density has limited value for detection of severe pneumococcal pneumonia.
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8.
  • Athlin, Simon, 1971-, et al. (författare)
  • Management of community-acquired pneumonia in immunocompetent adults : updated Swedish guidelines 2017
  • 2018
  • Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 50:4, s. 247-272
  • Forskningsöversikt (refereegranskat)abstract
    • Based on expert group work, Swedish recommendations for the management of community-acquired pneumonia in adults are here updated. The management of sepsis-induced hypotension is addressed in detail, including monitoring and parenteral therapy. The importance of respiratory support in cases of acute respiratory failure is emphasized. Treatment with high-flow oxygen and non-invasive ventilation is recommended. The use of statins or steroids in general therapy is not found to be fully supported by evidence. In the management of pleural infection, new data show favourable effects of tissue plasminogen activator and deoxyribonuclease installation. Detailed recommendations for the vaccination of risk groups are afforded.
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9.
  • Athlin, Simon, 1971-, et al. (författare)
  • Pneumococcal urinary antigen testing for antimicrobial guidance in community-acquired pneumonia : A register-based cohort study
  • 2022
  • Ingår i: Journal of Infection. - : Elsevier. - 0163-4453 .- 1532-2742. ; 85:2, s. 167-173
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To evaluate the effect of pneumococcal urinary antigen test (UAT) usage on broad-spectrum antibiotic treatment in community-acquired pneumonia (CAP).METHODS: Patients admitted to 32 Swedish hospitals between 2011 and 2014 were retrospectively included from the Swedish National Quality Register of CAP. Using propensity score matched data, stratified by CRB-65 score, we studied the effect of performing UAT and of positive test results on treatment with broad-spectrum β-lactam monotherapy (BSBM) and antibiotics with coverage for atypical bacteria compared to narrow-spectrum β-lactam monotherapy (NSBM).RESULTS: UAT was performed for 4,995/14,590 (34.2%) patients, 603/4,995 (12.1%) of whom had positive test results. At day three, performing UAT was not associated with decreased use of BSBM (OR 1.07, 95% CI 0.94-1.23) but was associated with increased atypical coverage among patients with CRB-65 score 2 (OR 1.47, 95% CI 1.06-2.02). A positive UAT was associated with decreased BSBM use (OR 0.39, 95% CI 0.25-0.60) and decreased atypical coverage (OR 0.25, 95% CI 0.16-0.37), predominantly in non-severe CAP. At day one, performing UAT was associated with atypical coverage among patients with CRB-65 scores 2 (OR 2.60, 95% CI 1.69-3.98) and 3-4 (OR 3.69, 95% CI 1.55-8.79), and a positive test reduced the odds of BSBM treatment among CRB-65 score 3-4 patients (OR 3.49, 95% CI 1.02-12.0).CONCLUSIONS: Performing UAT had no overall effect on decreasing the use of BSBM treatment by day three of hospitalization, yet non-severely ill patients with positive UAT results were less likely to be treated with BSBM and antibiotics with atypical coverage.
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11.
  • Berge, Andreas, et al. (författare)
  • The DENOVA score efficiently identifies patients with monomicrobial Enterococcus faecalis bacteremia where echocardiography is not necessary
  • 2019
  • Ingår i: Infection. - : Springer Science and Business Media LLC. - 0300-8126 .- 1439-0973. ; 47:1, s. 45-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Enterococcal bacteremia can be complicated by infective endocarditis (IE) and when suspected, transesophageal echocardiography (TEE) should be performed. The previously published NOVA score can identify patients with enterococcal bacteremia at risk for IE and we aimed to improve the score. Methods: Factors associated with IE were studied retrospectively in a population-based cohort of patients with monomicrobial Enterococcus faecalis bacteremia (MEFsB). Factors associated with IE in multivariable analysis were included in a new score system which was compared to the NOVA score and validated in a cohort of patients with MEFsB from another region. Results: Among 397 episodes of MEFsB, 44 episodes with IE were compared to those without IE. Long Duration of symptoms (≥ 7 days) and Embolization were associated with IE in the multivariate analysis and hence were added to the NOVA variables (Number of positive cultures, Origin of infection unknown, Valve disease, and Auscultation of murmur) to generate a novel score; DENOVA. The area under the curve in ROC analyses was higher for DENOVA (0.95) compared to NOVA (0.91) (p = 0.001). With a cutoff at ≥ 3 positive variables the DENOVA score has a sensitivity of 100% and specificity of 83% which is superior to the NOVA score (specificity 29%). The DENOVA score was applied to the validation cohort (26 IE episodes and 256 non-IE episodes) and the resulting sensitivity was 100% and the specificity was 85% compared to 35% for NOVA. Conclusions: The DENOVA score is a useful tool to identify patients with MEFsB where TEE is not needed.
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12.
  • Block, Nils, et al. (författare)
  • Bacterial meningitis : Aetiology, risk factors, disease trends and severe sequelae during 50 years in Sweden
  • 2022
  • Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 292:2, s. 350-364
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Bacterial meningitis (BM) is a rare but severe infection. Few population-based studies have characterised BM episodes and sequelae over long periods.Methods This was a population-based observational cohort study with national coverage, using data on aetiological pathogens, sex, premorbid conditions, steroid pretreatment, severe sequelae and birth, death and diagnosis dates collected from 10,339 patients with BM reported to the National Board of Health and Welfare in Sweden between 1964 and 2014.Results During the 50-year study period, the incidence of BM decreased in young children, but not in the elderly. The most common cause of BM was pneumococci (34%), followed by Haemophilus influenzae (26%), and meningococci (18%), mainly community acquired. Premorbid conditions were found in 20%. After the H. influenzae type b vaccine was introduced in 1993, the BM incidence decreased by 36%. Following pneumococcal conjugated vaccine introduction in 2009, the incidence and 30-day mortality from pneumococcal meningitis decreased by 64% and 100%, respectively, in previously healthy children, and the 30-day mortality decreased by 64% among comorbid adults. The BM incidence in immunosuppressed patients increased by 3% annually post vaccine introduction. The 30-day mortality was 3% in children and 14% in adults, and the rate of severe sequelae was 44%. On average, patients lost 11 years of healthy life due to BM.Conclusion The introduction of conjugated vaccines into the childhood vaccination program has reduced the incidence of BM in young children, but not in adults. Post vaccine introduction, patients present with more premorbid conditions and other bacterial causes of BM, emphasising the need for a correct diagnosis when treating these infections.
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13.
  • Brink, Magnus, 1960, et al. (författare)
  • Meropenem versus cefotaxime and ampicillin as empirical antibiotic treatment in adult bacterial meningitis: A quality registry study, 2008 to 2016
  • 2019
  • Ingår i: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 63:11
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2019 American Society for Microbiology. All Rights Reserved. Cefotaxime, alone or with ampicillin, is frequently used in empirical treatment of acute bacterial meningitis (ABM). Meropenem is a less extensively investigated alternative. The aim of the study was to investigate the effects of empirical treatment with meropenem compared to cefotaxime plus ampicillin on outcome in ABM. The study was based on data from the Swedish quality register for ABM collected between January 2008 and December 2016. Propensity score matching was performed to adjust for baseline differences between the groups. Mortality within 30 days was the primary outcome. The treatment regimens of interest were administered to 623 patients; 328 were given cefotaxime plus ampicillin whereas 295 received meropenem. Using propensity score matching, the 30-day mortality rates were 3.2% in the cefotaxime plus ampicillin group and 3.6% in the meropenem group. For matched cases, the odds ratio (OR) for 30-day mortality for meropenem versus cefotaxime plus ampicillin was 1.15 (confidence interval [CI], 0.41 to 3.22; P = 0.79). The OR for 90-day mortality was 1.47 (CI, 0.62 to 3.52; P = 0.38) and for unfavorable outcome was 1.10 (CI, 0.75 to 1.63; P = 0.62). The findings of our study indicate that meropenem is an effective empirical treatment option for adults with community-acquired ABM. However, to spare carbapenems, guidelines should continue to recommend third-generation cephalosporins as an empirical treatment for the majority of patients with ABM.
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14.
  • Browall, Sarah, et al. (författare)
  • Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types
  • 2014
  • Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 44:6, s. 1646-1657
  • Tidskriftsartikel (refereegranskat)abstract
    • Pneumococcal conjugated vaccines (PCVs) have shown protection against invasive pneumococcal disease by vaccine serotypes, but an increase in non-vaccine serotype disease has been observed. Type-specific effects on clinical manifestation need to be explored.Clinical data from 2096 adults and 192 children with invasive pneumococcal disease were correlated to pneumococcal molecular serotypes. Invasive disease potential for pneumococcal serotypes were calculated using 165 invasive and 550 carriage isolates from children.The invasive disease potential was lower for non-PCV13 compared to vaccine-type strains. Patients infected with non-PCV13 strains had more underlying diseases, were less likely to have pneumonia and, in adults, tended to have a higher mortality. Furthermore, patients infected with pneumococci belonging to clonal serotypes only expressing non-PCV13 capsules had a higher risk for septicaemia and mortality.PCV vaccination will probably lead to a decrease in invasive pneumococcal disease but an alteration in the clinical manifestation of invasive pneumococcal disease. Genetic lineages causing invasive pneumococcal disease in adults often express non-vaccine serotypes, which can expand after vaccination with an increased risk of infection in patients with underlying diseases.
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15.
  • Dejmek, Annika, et al. (författare)
  • Napsin A (TA02) is a useful alternative to thyroid transcription factor-1 (TTF-1) for the identification of pulmonary adenocarcinoma cells in pleural effusions
  • 2007
  • Ingår i: Diagnostic Cytopathology. - : Wiley. - 8755-1039 .- 1097-0339. ; 35:8, s. 493-497
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to test napsin A as a diagnostic marker of metastatic lung adenocarcinoma in pleural effusions, and to compare its performance with TTF-1. Napsin A and TTF-1 reactivities were determined immunohistochemically on.formalin-fixed paraffin embedded cell blocks from 50 pleural effusion (5 mesotheliomas, 10 mesothelial proliferations, 12 pulmonary, and 23 nonpulmonary metastases). The results were evaluated separately, and correlated to the final diagnoses. Concordant results were obtained in 48150 cases. TTF-1 and Napsin A were positive in 8112 and 10112 pulmonary adenocarcinomas, respectively. Both markers were negative in 42 cases, including two lung carcinomas. Napsin reactivity was found in more than 75% of the tumor cells in 9110 positive cases, whereas TTF-1 reactivity was seen in more than 75% of the tumor cells in 218 positive cases only (P < 0.05). This makes napsin A an alternative to TTF-1 in cytological diagnosis of effusions in which tumor cells may be scanty.
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16.
  • Dillner, Joakim, et al. (författare)
  • Long term predictive values of cytology and human papillomavirus testing in cervical cancer screening: joint European cohort study.
  • 2008
  • Ingår i: BMJ: British Medical Journal. - : BMJ. - 1756-1833 .- 0959-8138 .- 1468-5833. ; 337
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To obtain large scale and generalisable data on the long term predictive value of cytology and human papillomavirus (HPV) testing for development of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+). DESIGN: Multinational cohort study with joint database analysis. SETTING: Seven primary HPV screening studies in six European countries. PARTICIPANTS: 24,295 women attending cervical screening enrolled into HPV screening trials who had at least one cervical cytology or histopathology examination during follow-up. MAIN OUTCOME MEASURE: Long term cumulative incidence of CIN3+. RESULTS: The cumulative incidence rate of CIN3+ after six years was considerably lower among women negative for HPV at baseline (0.27%, 95% confidence interval 0.12% to 0.45%) than among women with negative results on cytology (0.97%, 0.53% to 1.34%)). By comparison, the cumulative incidence rate for women with negative cytology results at the most commonly recommended screening interval in Europe (three years) was 0.51% (0.23% to 0.77%). The cumulative incidence rate among women with negative cytology results who were positive for HPV increased continuously over time, reaching 10% at six years, whereas the rate among women with positive cytology results who were negative for HPV remained below 3%. CONCLUSIONS: A consistently low six year cumulative incidence rate of CIN3+ among women negative for HPV suggests that cervical screening strategies in which women are screened for HPV every six years are safe and effective.
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18.
  • Froding, Inga, et al. (författare)
  • Extended-Spectrum-beta-Lactamase- and Plasmid AmpC-Producing Escherichia coli Causing Community-Onset Bloodstream Infection : Association of Bacterial Clones and Virulence Genes with Septic Shock, Source of Infection, and Recurrence
  • 2020
  • Ingår i: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 64:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Invasive infections due to extended-spectrum-beta-lactamase- and pAmpC-producing Escherichia coli (ESBL/pAmpC-EC) are an important cause of morbidity, often caused by the high-risk clone sequence type (ST131) and isolates classified as extraintestinal pathogenic E. coli (ExPEC). The relative influence of host immunocompetence versus microbiological virulence factors in the acquisition and outcome of bloodstream infections (BSI) is poorly understood. Herein, we used whole-genome sequencing on 278 blood culture isolates of ESBL/pAmpC-EC from 260 patients with community-onset BSI collected from 2012 to 2015 in Stockholm to study the association of virulence genes, sequence types, and antimicrobial resistance with severity of disease, infection source, ESBL/pAmpC-EC BSI low-risk patients, and patients with repeated episodes. ST131 subclade C2 comprised 29% of all patients. Factors associated with septic shock in multivariable analysis were patient host factors (hematologic cancer or transplantation and reduced daily living activity), presence of the E. coli virulence factor iss (increased serum survival), absence of phenotypic multidrug resistance, and absence of the genes pap and hsp. Adhesins, particularly pap, were associated with urinary tract infection (UTI) source, while isolates from post-prostate biopsy sepsis had a low overall number of virulence operons, including adhesins, and commonly belonged to ST131 clades A, B, and subclade C1, ST1193, and ST648. ST131 was associated with recurrent episodes. In conclusion, the most interesting finding is the association of iss with septic shock. Adhesins are important for UTI pathogenesis, while otherwise low-pathogenic isolates from the microbiota can cause post-prostate biopsy sepsis.
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19.
  • Glimaker, Martin, et al. (författare)
  • Etiology, clinical presentation, outcome and the effect of initial management in immunocompromised patients with community acquired bacterial meningitis
  • 2020
  • Ingår i: Journal of Infection. - : W B SAUNDERS CO LTD. - 0163-4453 .- 1532-2742. ; 80:3, s. 291-297
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim was to analyze differences in clinical presentation, etiology, management, and outcome between immunocompromised and immunocompetent patients with acute bacterial meningitis (ABM). Methods: Data were extracted from 1056 adult ABM patients prospectively registered in the national Swedish quality register for ABM during 2008-2017. Primary endpoint was 30-day mortality and secondary endpoints 90-day mortality and unfavorable outcome. Results: An immunocompromised state was observed in 352 (33%) of the 1056 patients. Streptococcus pneumoniae dominated in both immunocompromised and immunocompetent patients (53% in both groups), whereas L monocytogenes occurred in 11% and 2%, respectively. The unadjusted odds ratio (OR) for 30-day mortality in immunocompromised compared to immunocompetent patients was 1.68 (95% confidence interval (CI): 1.07-2.63). Adjusted for age, sex, and mental status on admission the OR was 1.34 (CI: 0.82-2.21). Adjusted also for time to antibiotic treatment and corticosteroids the OR was 1.10 (CI: 0.59-2.05), and in patients without Listeria meningitis 0.98 (CI: 0.50-1.90). Although, the ORs were higher for 90-day mortality and unfavorable outcome the effects of adjustments were similar. Conclusion: Mortality in immunocompromised patients with ABM is only moderately increased unless caused by Listeria. This difference is further reduced in patients given early antibiotic treatment and adjunctive corticosteroids. Funding: This work was supported by Stockholm County Council.
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20.
  • Glimåker, Martin, et al. (författare)
  • Lumbar Puncture Performed Promptly or After Neuroimaging in Acute Bacterial Meningitis in Adults : A Prospective National Cohort Study Evaluating Different Guidelines.
  • 2018
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 66:3, s. 321-328
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Early treatment is pivotal for favorable outcome in acute bacterial meningitis (ABM). Lumbar puncture (LP) is the diagnostic key. The aim was to evaluate the effect on outcome of adherence to European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA), and Swedish guidelines regarding neuroimaging before LP.Methods: The cohort comprised 815 adult ABM patients in Sweden registered prospectively between 2008 and 2015. Primary endpoint was in-hospital mortality and secondary endpoint was favorable outcome at 2-6 months of follow-up.Results: Indications for neuroimaging before LP existed in 7%, 32%, and 65% according to Swedish, ESCMID, and IDSA guidelines, respectively. The adjusted odds ratio (aOR) was 0.48 (95% confidence interval [CI], .26-.89) for mortality and 1.52 (95% CI, 1.08-2.12) for favorable outcome if Swedish guidelines were followed. ESCMID guideline adherence resulted in aOR of 0.68 (95% CI, .38-1.23) for mortality and 1.05 (95% CI, .75-1.47) for favorable outcome. Following IDSA recommendations resulted in aOR of 1.09 (95% CI, .61-1.95) for mortality and 0.59 (95% CI, .42-.82) for favorable outcome. Performing prompt vs neuroimaging-preceded LP was associated with aOR of 0.38 (95% CI, .18-.77) for mortality and 2.11 (95% CI, 1.47-3.00) for favorable outcome. The beneficial effect of prompt LP was observed regardless of mental status and immunosuppression.Conclusions: Adherence to Swedish guidelines in ABM is associated with decreased mortality and increased favorable outcome in contrast to adherence to ESCMID or IDSA recommendations. Our findings support that impaired mental status and immunocompromised state should not be considered indications for neuroimaging before LP in patients with suspected ABM.
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21.
  • Karlsson Valik, John, et al. (författare)
  • Peripheral Oxygen Saturation Facilitates Assessment of Respiratory Dysfunction in the Sequential Organ Failure Assessment Score With Implications for the Sepsis-3 Criteria
  • 2022
  • Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 50:3, s. e272-e283
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Sequential Organ Failure Assessment score is the basis of the Sepsis-3 criteria and requires arterial blood gas analysis to assess respiratory function. Peripheral oxygen saturation is a noninvasive alternative but is not included in neither Sequential Organ Failure Assessment score nor Sepsis-3. We aimed to assess the association between worst peripheral oxygen saturation during onset of suspected infection and mortality.DESIGN: Cohort study of hospital admissions from a main cohort and emergency department visits from four external validation cohorts between year 2011 and 2018. Data were collected from electronic health records and prospectively by study investigators.SETTING: Eight academic and community hospitals in Sweden and Canada.PATIENTS: Adult patients with suspected infection episodes.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: The main cohort included 19,396 episodes (median age, 67.0 [53.0–77.0]; 9,007 [46.4%] women; 1,044 [5.4%] died). The validation cohorts included 10,586 episodes (range of median age, 61.0–76.0; women 42.1–50.2%; mortality 2.3–13.3%). Peripheral oxygen saturation levels 96–95% were not significantly associated with increased mortality in the main or pooled validation cohorts. At peripheral oxygen saturation 94%, the adjusted odds ratio of death was 1.56 (95% CI, 1.10–2.23) in the main cohort and 1.36 (95% CI, 1.00–1.85) in the pooled validation cohorts and increased gradually below this level. Respiratory assessment using peripheral oxygen saturation 94–91% and less than 91% to generate 1 and 2 Sequential Organ Failure Assessment points, respectively, improved the discrimination of the Sequential Organ Failure Assessment score from area under the receiver operating characteristics 0.75 (95% CI, 0.74–0.77) to 0.78 (95% CI, 0.77–0.80; p < 0.001). Peripheral oxygen saturation/Fio2 ratio had slightly better predictive performance compared with peripheral oxygen saturation alone, but the clinical impact was minor.CONCLUSIONS: These findings provide evidence for assessing respiratory function with peripheral oxygen saturation in the Sequential Organ Failure Assessment score and the Sepsis-3 criteria. Our data support using peripheral oxygen saturation thresholds 94% and 90% to get 1 and 2 Sequential Organ Failure Assessment respiratory points, respectively. This has important implications primarily for emergency practice, rapid response teams, surveillance, research, and resource-limited settings.
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22.
  • Karlsson Valik, John, et al. (författare)
  • Validation of automated sepsis surveillance based on the Sepsis-3 clinical criteria against physician record review in a general hospital population : observational study using electronic health records data
  • 2020
  • Ingår i: BMJ Quality and Safety. - : BMJ Publishing Group Ltd. - 2044-5415 .- 2044-5423. ; 29:9, s. 735-745
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Surveillance of sepsis incidence is important for directing resources and evaluating quality-of-care interventions. The aim was to develop and validate a fully-automated Sepsis-3 based surveillance system in non-intensive care wards using electronic health record (EHR) data, and demonstrate utility by determining the burden of hospital-onset sepsis and variations between wards.Methods: A rule-based algorithm was developed using EHR data from a cohort of all adult patients admitted at an academic centre between July 2012 and December 2013. Time in intensive care units was censored. To validate algorithm performance, a stratified random sample of 1000 hospital admissions (674 with and 326 without suspected infection) was classified according to the Sepsis-3 clinical criteria (suspected infection defined as having any culture taken and at least two doses of antimicrobials administered, and an increase in Sequential Organ Failure Assessment (SOFA) score by >2 points) and the likelihood of infection by physician medical record review.Results: In total 82 653 hospital admissions were included. The Sepsis-3 clinical criteria determined by physician review were met in 343 of 1000 episodes. Among them, 313 (91%) had possible, probable or definite infection. Based on this reference, the algorithm achieved sensitivity 0.887 (95% CI: 0.799 to 0.964), specificity 0.985 (95% CI: 0.978 to 0.991), positive predictive value 0.881 (95% CI: 0.833 to 0.926) and negative predictive value 0.986 (95% CI: 0.973 to 0.996). When applied to the total cohort taking into account the sampling proportions of those with and without suspected infection, the algorithm identified 8599 (10.4%) sepsis episodes. The burden of hospital-onset sepsis (>48 hour after admission) and related in-hospital mortality varied between wards.Conclusions: A fully-automated Sepsis-3 based surveillance algorithm using EHR data performed well compared with physician medical record review in non-intensive care wards, and exposed variations in hospital-onset sepsis incidence between wards.
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23.
  • Lamproudis, Anastasios, et al. (författare)
  • Improving the Timeliness of Early Prediction Models for Sepsis through Utility Optimization
  • 2022
  • Ingår i: 2022 IEEE 34th International Conference on Tools with Artificial Intelligence (ICTAI). ; , s. 1062-1069
  • Konferensbidrag (refereegranskat)abstract
    • Early prediction of sepsis can facilitate early intervention and lead to improved clinical outcomes. However, for early prediction models to be clinically useful, and also to reduce alarm fatigue, detection of sepsis needs to be timely with respect to onset, being neither too late nor too early. In this paper, we propose a utility-based loss function for training early prediction models, where utility is defined by a function according to when the predictions are made and in relation to onset as well as to specified early, optimal and late time points. Two versions of the utility-based loss function are evaluated and compared to a cross-entropy loss baseline. Experimental results, using real clinical data from electronic health records, show that incorporating the utility-based loss function leads to superior multimodal early prediction models, detecting sepsis both more accurately and more timely. We argue that improving the timeliness of early prediction models is important for increasing their utility and acceptance in a clinical setting.
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24.
  • Naucler, Pontus, et al. (författare)
  • Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA testing in primary cervical cancer screening.
  • 2009
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 101:2, s. 88-99
  • Tidskriftsartikel (refereegranskat)abstract
    • Primary cervical screening with both human papillomavirus (HPV) DNA testing and cytological examination of cervical cells with a Pap test (cytology) has been evaluated in randomized clinical trials. Because the vast majority of women with positive cytology are also HPV DNA positive, screening strategies that use HPV DNA testing as the primary screening test may be more effective.
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25.
  • Naucler, Pontus, et al. (författare)
  • HAI-Proactive : Development of an Automated Surveillance System for Healthcare-Associated Infections in Sweden
  • 2020
  • Ingår i: Infection control and hospital epidemiology. - : Cambridge University Press. - 0899-823X .- 1559-6834. ; 41, s. S39-S39
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Healthcare-associated infection (HAI) surveillance is essential for most infection prevention programs and continuous epidemiological data can be used to inform healthcare personal, allocate resources, and evaluate interventions to prevent HAIs. Many HAI surveillance systems today are based on time-consuming and resource-intensive manual reviews of patient records. The objective of HAI-proactive, a Swedish triple-helix innovation project, is to develop and implement a fully automated HAI surveillance system based on electronic health record data. Furthermore, the project aims to develop machine-learning–based screening algorithms for early prediction of HAI at the individual patient level. Methods: The project is performed with support from Sweden’s Innovation Agency in collaboration among academic, health, and industry partners. Development of rule-based and machine-learning algorithms is performed within a research database, which consists of all electronic health record data from patients admitted to the Karolinska University Hospital. Natural language processing is used for processing free-text medical notes. To validate algorithm performance, manual annotation was performed based on international HAI definitions from the European Center for Disease Prevention and Control, Centers for Disease Control and Prevention, and Sepsis-3 criteria. Currently, the project is building a platform for real-time data access to implement the algorithms within Region Stockholm. Results: The project has developed a rule-based surveillance algorithm for sepsis that continuously monitors patients admitted to the hospital, with a sensitivity of 0.89 (95% CI, 0.85–0.93), a specificity of 0.99 (0.98–0.99), a positive predictive value of 0.88 (0.83–0.93), and a negative predictive value of 0.99 (0.98–0.99). The healthcare-associated urinary tract infection surveillance algorithm, which is based on free-text analysis and negations to define symptoms, had a sensitivity of 0.73 (0.66–0.80) and a positive predictive value of 0.68 (0.61–0.75). The sensitivity and positive predictive value of an algorithm based on significant bacterial growth in urine culture only was 0.99 (0.97–1.00) and 0.39 (0.34–0.44), respectively. The surveillance system detected differences in incidences between hospital wards and over time. Development of surveillance algorithms for pneumonia, catheter-related infections and Clostridioides difficile infections, as well as machine-learning–based models for early prediction, is ongoing. We intend to present results from all algorithms. Conclusions: With access to electronic health record data, we have shown that it is feasible to develop a fully automated HAI surveillance system based on algorithms using both structured data and free text for the main healthcare-associated infections.Funding: Sweden’s Innovation Agency and Stockholm County CouncilDisclosures: None
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26.
  • Naucler, Pontus, et al. (författare)
  • HPV type-specific risks of high-grade CIN during 4 years of follow-up : A population-based prospective study
  • 2007
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 97:1, s. 129-132
  • Tidskriftsartikel (refereegranskat)abstract
    • We followed a population-based cohort of 5696 women, 32 - 38 years of age, by registry linkage with cytology and pathology registries during a mean follow-up time of 4.1 years to assess the importance for CIN2 + development of type-specific HPV DNA positivity at baseline. HPV 16, 31 and 33 conveyed the highest risks and were responsible for 33.1, 18.3 and 7.7% of CIN2 + cases, respectively. Women infected with HPV 18, 35, 39, 45, 51, 52, 56, 58, 59 and 66 had significantly lower risks of CIN2 + than women infected with HPV 16. After adjustment for infection with other HPV types, HPV types 35, 45, 59 and 66 had no detectable association with CIN2 +. In summary, the different HPV types found in cervical cancer show distinctly different CIN2 + risks, with high risks being restricted to HPV 16 and its close relatives HPV 31 and HPV 33.
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27.
  • Naucler, Pontus, et al. (författare)
  • Human papillomavirus and Papanicolaou tests to screen for cervical cancer.
  • 2007
  • Ingår i: New England Journal of Medicine. - Boston, Massachusetts : Massachusetts medical society. - 0028-4793 .- 1533-4406. ; 357:16, s. 1589-97
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Screening for cervical cancer based on testing for human papillomavirus (HPV) increases the sensitivity of detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia, but whether this gain represents overdiagnosis or protection against future high-grade cervical epithelial neoplasia or cervical cancer is unknown. Methods In a population-based screening program in Sweden, 12,527 women 32 to 38 years of age were randomly assigned at a 1:1 ratio to have an HPV test plus a Papanicolaou (Pap) test (intervention group) or a Pap test alone (control group). Women with a positive HPV test and a normal Pap test result were offered a second HPV test at least 1 year later, and those who were found to be persistently infected with the same high-risk type of HPV were then offered colposcopy with cervical biopsy. A similar number of double-blinded Pap smears and colposcopies with biopsy were performed in randomly selected women in the control group. Comprehensive registry data were used to follow the women for a mean of 4.1 years. The relative rates of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected at enrollment and at subsequent screening examinations were calculated. Results At enrollment, the proportion of women in the intervention group who were found to have lesions of grade 2 or 3 cervical intraepithelial neoplasia or cancer was 51% greater (95% confidence interval [CI], 13 to 102) than the proportion of women in the control group who were found to have such lesions. At subsequent screening examinations, the proportion of women in the intervention group who were found to have grade 2 or 3 lesions or cancer was 42% less (95% CI, 4 to 64) and the proportion with grade 3 lesions or cancer was 47% less (95% CI, 2 to 71) than the proportions of control women who were found to have such lesions. Women with persistent HPV infection remained at high risk for grade 2 or 3 lesions or cancer after referral for colposcopy. Conclusions The addition of an HPV test to the Pap test to screen women in their mid-30s for cervical cancer reduces the incidence of grade 2 or 3 cervical intraepithelial neoplasia or cancer detected by subsequent screening examinations.
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28.
  • Naucler, Pontus, et al. (författare)
  • Human papillomavirus genotypes in cervical cancers in Mozambique.
  • 2004
  • Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 85:Pt 8, s. 2189-2190
  • Tidskriftsartikel (refereegranskat)abstract
    • The distribution of human papillomavirus (HPV) types in cervical cancers is essential for design and evaluation of HPV type-specific vaccines. To follow up on a previous report that HPV types 35 and 58 were the dominant HPV types in cervical neoplasia in Mozambique, the HPV types in a consecutive case series of 74 invasive cervical cancers in Mozambique were determined. The most common worldwide major oncogenic HPV types 16 and 18 were present in 69 % of cervical cancers, suggesting that a vaccine targeting HPV-16 and -18 would have a substantial impact on cervical cancer also in Mozambique.
  •  
29.
  • Naucler, Pontus, et al. (författare)
  • Human papillomavirus type-specific risk of cervical cancer in a population with high human immunodeficiency virus prevalence: case-control study
  • 2011
  • Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 92:12, s. 2784-2791
  • Tidskriftsartikel (refereegranskat)abstract
    • There are limited data on human papillomavirus (HPV) type-specific cervical cancer risk among human immunodeficiency virus (HIV)-positive women. Previous studies have suggested that HPV 16 would be relatively less important as a causative agent among HIV-positive compared with HIV-negative women. This study investigates HPV type-specific cervical cancer risk in a population in which HIV is endemic. At the Central Hospital, Maputo, Mozambique, 221 cervical cancer cases and 203 hospital-based controls were consecutively enrolled. HPV typing from cervical samples, HIV testing and recording of socio-demographic factors were performed. Logistic regression modelling was used to assess HPV type-specific risk and effect modification between HIV and HPV infection. Infection with HPV 16, 18 and 'high-risk non-HPV 16/18 types' (HPV 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59) was associated with cervical cancer in both crude and adjusted analyses. HPV 16 and 18 were the most common types detected in cancer biopsies among both HIV-negative and HIV-positive women. There was no significant evidence of effect modification between any HPV type and HIV infection, and there were no significant differences in the HPV type-specific prevalence when cervical cancers among HIV-positive and HIV-negative women were compared. Within the limitations of the study, the relative importance of different HPV types in cervical carcinogenesis appears not to be modified greatly by HIV infection, suggesting that HPV vaccines might not need to be type-specifically modified to be suitable for populations where HIV is endemic.
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30.
  • Naucler, Pontus, et al. (författare)
  • Seroprevalence of human papillomaviruses and Chlamydia trachomatis and cervical cancer risk: nested case-control study.
  • 2007
  • Ingår i: Journal of General Virology. - : Microbiology Society. - 1465-2099 .- 0022-1317. ; 88:3, s. 814-822
  • Tidskriftsartikel (refereegranskat)abstract
    • A nested case–control study of invasive and in situ cervical cancer was performed within a community-based cohort of 13 595 Taiwanese women assembled in 1991, with a follow-up period of 9 years. Baseline serum or plasma samples were analysed for antibodies against human papillomavirus (HPV) types 6, 16 and 18 and Chlamydia trachomatis. In total, 114 cases (42 incident cases identified during follow-up and 72 prevalent cases identified at baseline) and 519 matched controls were included in the study. HPV-16 seropositivity was strongly associated with cervical cancer (OR=6.33; 95 % CI 3.45–11.62). Overall, C. trachomatis was not associated with cervical cancer, but was associated with cervical cancer in analyses restricted to incident cases of cancer (OR=2.94; 95 % CI 1.17–7.42) or to cases in which serum samples were analysed (OR=3.13; 95 % CI 1.16–8.47). An antagonistic interaction between HPV-6 and -16 was found in a multiplicative model. These results suggest that different HPV types might interfere in cervical carcinogenesis and that C. trachomatis is associated with cervical cancer in prospective studies, and support the notion that HPV-16 seropositivity is strongly associated with cervical cancer.
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31.
  • Naucler, Pontus (författare)
  • Targeting the human papillomavirus for prevention of cervical cancer
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Different types of human papillomavirus (HPV) vary in the extent they cause precursor lesions (CIN) and cancer. There are limited long-term efficacy data on HPV testing in primary screening Among 72 cervical cancers in Mozambique, HPV 16 and 18 were the most frequent HPV types (69% of cases). Comparing 108 cervical cancers cases and 517 matched controls nested within a population-based cohort in Taiwan, HPV 16 seropositivity implied a 6-fold increased cancer risk. In a cohort of 5696 women in Sweden, HPV types 16, 31 and 33 conveyed the highest risks for future high-grade CIN (CIN 2+), attributing to 33.1%, 18.3% and 7.7% of CIN 2+ cases, respectively. In a pooled analysis of seven European longitudinal studies of HPV-based cervical screening, the cumulative incidence rate of CIN grade 3 or worse (CIN 3+) was higher after 3 years among women with normal cytology than among women with a negative HPV test after 6 years. Finally, in a randomized cervical cancer screening trial in Sweden, adding testing for HPV persistence resulted in a 51% (95% CI: 13-102) increase of CIN 2+ at prevalent screening, which was followed by a reduction of 42% (95% CI: 4-76) of CIN 2+ at incident screening. In conclusion, HPV-based cervical cancer screening protects against future CIN 2+, and the long-term protective effect should enable extended screening intervals to 6 years. Albeit HPV 16 is the most important carcinogenic HPV type all over the world, different ?high-risk? HPV types convey distinctly different risks for CIN 2+, which should be considered in design of screening tests and vaccines.
  •  
32.
  • Ny, Sofia, et al. (författare)
  • Community carriage of ESBL-producing Escherichia coli is associated with strains of low pathogenicity : a Swedish nationwide study
  • 2017
  • Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press. - 0305-7453 .- 1460-2091. ; 72:2, s. 582-588
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Community carriage of ESBL-producing Escherichia coli (EPE) is common worldwide and there is a need to understand the connection between carriage and infection. We compared the molecular characteristics of EPE among Swedish community carriers with those of EPE causing invasive infections.METHODS: We collected 2134 faecal samples from randomly selected Swedish inhabitants and examined them for the presence of EPE. All participating volunteers answered a questionnaire about putative risk factors for EPE carriage. Suspected EPE isolates (n = 418) from patients with bloodstream infection (BSI) were collected from Swedish laboratories. Isolates were genotypically and phenotypically characterized.RESULTS: Our results show that the EPE population found in carriers generally had lower pathogenicity compared with the isolates from BSIs, since carriers had a lower proportion of E. coli belonging to phylogroup B2, ST131 and ST131 subclone H30-Rx. Isolates from carriers also had lower levels of multiresistance. The Swedish carriage rate of EPE was 4.7% (101/2134) among healthy volunteers. Risk factors associated with carriage were travel to countries in Asia (OR = 3.6, 95% CI = 1.4-9.2) and Africa (OR = 3.6, 95% CI = 1.7-7.7) and a diet without pork (OR = 0.5, 95% CI = 0.3-0.8 for pork eaters).CONCLUSIONS: E. coli host factors previously associated with higher pathogenicity were all more common in BSIs compared with carriers. This indicates that the risk of invasive infection with EPE may be relatively modest in many community carriers and that EPE carriage of high-risk strains should be the focus of attention for prevention.
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33.
  • Rhedin, Samuel, et al. (författare)
  • Myxovirus resistance protein A for discriminating between viral and bacterial lower respiratory tract infections in children- The TREND study
  • 2022
  • Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 28:9, s. 1251-1257
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Discriminating between viral and bacterial lower respiratory tract infection (LRTI) in children is challenging, leading to an excessive use of antibiotics. Myxovirus resistance protein A (MxA) is a promising biomarker for viral infections. The primary aim of the study was to assess differences in blood MxA levels between children with viral and bacterial LRTI. Secondary aims were to assess differences in blood MxA levels between children with viral LRTI and asymptomatic controls and to assess MxA levels in relation to different respiratory viruses. Methods: Children with LRTI were enrolled as cases at Sachs' Children and Youth Hospital, Stockholm, Sweden. Nasopharyngeal aspirates and blood samples for analysis of viral PCR, MxA, and C-reactive protein were systematically collected from all study subjects in addition to standard laboratory/radiology assessment. Aetiology was defined according to an algorithm based on laboratory and radiological findings. Asymptomatic children with minor surgical disease were enrolled as controls. Results: MxA levels were higher in children with viral LRTI (n = 242) as compared to both bacterial (n = 5) LRTI (p < 0.01, area under the curve (AUC) 0.90, 95% CI: 0.81 to 0.99), and controls (AUC 0.92, 95% CI: 0.88 to 0.95). In the subgroup of children with pneumonia diagnosis, a cutoff of MxA 430 mg/l discriminated between viral (n = 29) and bacterial (n = 4) aetiology with 93% (95% CI: 78-99%) sensi-tivity and 100% (95% CI: 51-100%) specificity (AUC 0.98, 95% CI: 0.94 to 1.00). The highest MxA levels were seen in cases PCR positive for influenza (median MxA 1699 mg/l, interquartile range: 732 to 2996) and respiratory syncytial virus (median MxA 1115 mg/l, interquartile range: 679 to 2489). Discussion: MxA accurately discriminated between viral and bacterial aetiology in children with LRTI, particularly in the group of children with pneumonia diagnosis, but the number of children with bacterial LRTI was low.
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34.
  • Ryding, Janka, et al. (författare)
  • Seroepidemiology as basis for design of a human papillomavirus vaccination program.
  • 2008
  • Ingår i: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; Aug 8, s. 5263-5268
  • Tidskriftsartikel (refereegranskat)abstract
    • We have performed a serological survey of HPV type 16-antibody prevalence by age and sex in Sweden and used it as a basis for modelling the optimal vaccination strategies in this population. Samples of 3317 subjects were tested for HPV16-specific antibodies. The observed age-specific seroprevalences along with sexual behaviour data were used to infer parameter values for a mathematical model representing Sweden and the preventive effect of possible strategies estimated. By the year 2055, vaccination of females starting at age 12 in 2008 was most efficient, estimated to prevent 5.8 million cumulative HPV16 infections. Catch-up programs had a strong additional preventive effect. Vaccination also targeting males increased protective effect by about 4%, but had lower preventive effect per vaccination given. Addition of an HPV serosurvey to existing models and data has enabled us to estimate effect of different vaccination strategies, optimized to the HPV epidemiology in our population.
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35.
  • Strålin, Kristoffer, et al. (författare)
  • Design of a national patient-centred clinical pathway for sepsis in Sweden
  • 2023
  • Ingår i: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 55:10, s. 716-724
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The World Health Organization has adopted a resolution on sepsis and urged member states to develop national processes to improve sepsis care. In Sweden, sepsis was selected as one of the ten first diagnoses to be addressed, when the Swedish government in 2019 allocated funds for patient-centred clinical pathways in healthcare. A national multidisciplinary working group, including a patient representative, was appointed to develop the patient-centred clinical pathway for sepsis.METHODS: The working group mapped challenges and needs surrounding sepsis care and included a survey sent to all emergency departments (ED) in Sweden, and then designed a patient-centred clinical pathway for sepsis.RESULTS: The working group decided to focus on the following four areas: (1) sepsis alert for early detection and management optimisation for the most severely ill sepsis patients in the ED; (2) accurate sepsis diagnosis coding; (3) structured information to patients at discharge after sepsis care and (4) structured telephone follow-up after sepsis care. A health-economic analysis indicated that the implementation of the clinical pathway for sepsis will most likely not drive costs. An important aspect of the clinical pathway is implementing continuous monitoring of performance and process indicators. A national working group is currently building up such a system for monitoring, focusing on extraction of this information from the electronic health records systems.CONCLUSION: A national patient-centred clinical pathway for sepsis has been developed and is currently being implemented in Swedish healthcare. We believe that the clinical pathway and the accompanying monitoring will provide a more efficient and equal sepsis care and improved possibilities to monitor and further develop sepsis care in Sweden.
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36.
  • Valik, John Karlsson, et al. (författare)
  • Predicting sepsis onset using a machine learned causal probabilistic network algorithm based on electronic health records data
  • 2023
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Sepsis is a leading cause of mortality and early identification improves survival. With increasing digitalization of health care data automated sepsis prediction models hold promise to aid in prompt recognition. Most previous studies have focused on the intensive care unit (ICU) setting. Yet only a small proportion of sepsis develops in the ICU and there is an apparent clinical benefit to identify patients earlier in the disease trajectory. In this cohort of 82,852 hospital admissions and 8038 sepsis episodes classified according to the Sepsis-3 criteria, we demonstrate that a machine learned score can predict sepsis onset within 48 h using sparse routine electronic health record data outside the ICU. Our score was based on a causal probabilistic network model-SepsisFinder-which has similarities with clinical reasoning. A prediction was generated hourly on all admissions, providing a new variable was registered. Compared to the National Early Warning Score (NEWS2), which is an established method to identify sepsis, the SepsisFinder triggered earlier and had a higher area under receiver operating characteristic curve (AUROC) (0.950 vs. 0.872), as well as area under precision-recall curve (APR) (0.189 vs. 0.149). A machine learning comparator based on a gradient-boosting decision tree model had similar AUROC (0.949) and higher APR (0.239) than SepsisFinder but triggered later than both NEWS2 and SepsisFinder. The precision of SepsisFinder increased if screening was restricted to the earlier admission period and in episodes with bloodstream infection. Furthermore, the SepsisFinder signaled median 5.5 h prior to antibiotic administration. Identifying a high-risk population with this method could be used to tailor clinical interventions and improve patient care.
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37.
  • van der Werff, S. D., et al. (författare)
  • The accuracy of fully automated algorithms for surveillance of healthcare-associated urinary tract infections in hospitalized patients
  • 2021
  • Ingår i: Journal of Hospital Infection. - : Elsevier BV. - 0195-6701 .- 1532-2939. ; 110, s. 139-147
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Surveillance for healthcare-associated infections such as healthcareassociated urinary tract infections (HA-UTI) is important for directing resources and evaluating interventions. However, traditional surveillance methods are resourceintensive and subject to bias.Aim: To develop and validate a fully automated surveillance algorithm for HA-UTI using electronic health record (EHR) data.Methods: Five algorithms were developed using EHR data from 2979 admissions at Karolinska University Hospital from 2010 to 2011: (1) positive urine culture (UCx); (2) positive UCx + UTI codes (International Statistical Classification of Diseases and Related Health Problems, 10th revision); (3) positive UCx + UTI-specific antibiotics; (4) positive UCx + fever and/or UTI symptoms; (5) algorithm 4 with negation for fever without UTI symptoms. Natural language processing (NLP) was used for processing free-text medical notes. The algorithms were validated in 1258 potential UTI episodes from January to March 2012 and results extrapolated to all UTI episodes within this period (N 1/4 16,712). The reference standard for HA-UTIs was manual record review according to the European Centre for Disease Prevention and Control (and US Centers for Disease Control and Prevention) definitions by trained healthcare personnel.Findings: Of the 1258 UTI episodes, 163 fulfilled the ECDC HA-UTI definition and the algorithms classified 391, 150, 189, 194, and 153 UTI episodes, respectively, as HA-UTI. Algorithms 1, 2, and 3 had insufficient performances. Algorithm 4 achieved better performance and algorithm 5 performed best for surveillance purposes with sensitivity 0.667 (95% confidence interval: 0.594-0.733), specificity 0.997 (0.996-0.998), positive predictive value 0.719 (0.624-0.807) and negative predictive value 0.997 (0.996-0.997).Conclusion: A fully automated surveillance algorithm based on NLP to find UTI symptoms in free-text had acceptable performance to detect HA-UTI compared to manual record review. Algorithms based on administrative and microbiology data only were not sufficient.
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38.
  • van Mourik, Maaike S. M., et al. (författare)
  • PRAISE : providing a roadmap for automated infection surveillance in Europe
  • 2021
  • Ingår i: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 27, s. S3-S19
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Healthcare-associated infections (HAI) are among the most common adverse events of medical care. Surveillance of HAI is a key component of successful infection prevention programmes. Conventional surveillance - manual chart review - is resource intensive and limited by concerns regarding interrater reliability. This has led to the development and use of automated surveillance (AS). Many AS systems are the product of in-house development efforts and heterogeneous in their design and methods. With this roadmap, the PRAISE network aims to provide guidance on how to move AS from the research setting to large-scale implementation, and how to ensure the delivery of surveillance data that are uniform and useful for improvement of quality of care. Methods: The PRAISE network brings together 30 experts from ten European countries. This roadmap is based on the outcome of two workshops, teleconference meetings and review by an independent panel of international experts. Results: This roadmap focuses on the surveillance of HAI within networks of healthcare facilities for the purpose of comparison, prevention and quality improvement initiatives. The roadmap does the following: discusses the selection of surveillance targets, different organizational and methodologic approaches and their advantages, disadvantages and risks; defines key performance requirements of AS systems and suggestions for their design; provides guidance on successful implementation and maintenance; and discusses areas of future research and training requirements for the infection prevention and related disciplines. The roadmap is supported by accompanying documents regarding the governance and information technology aspects of implementing AS. Conclusions: Large-scale implementation of AS requires guidance and coordination within and across surveillance networks. Transitions to large-scale AS entail redevelopment of surveillance methods and their interpretation, intensive dialogue with stakeholders and the investment of considerable resources. This roadmap can be used to guide future steps towards implementation, including designing solutions for AS and practical guidance checklists. (C) 2021 Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.
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39.
  • Verberk, Janneke D. M., et al. (författare)
  • The augmented value of using clinical notes in semi-automated surveillance of deep surgical site infections after colorectal surgery
  • 2023
  • Ingår i: Antimicrobial Resistance and Infection Control. - 2047-2994. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundIn patients who underwent colorectal surgery, an existing semi-automated surveillance algorithm based on structured data achieves high sensitivity in detecting deep surgical site infections (SSI), however, generates a significant number of false positives. The inclusion of unstructured, clinical narratives to the algorithm may decrease the number of patients requiring manual chart review. The aim of this study was to investigate the performance of this semi-automated surveillance algorithm augmented with a natural language processing (NLP) component to improve positive predictive value (PPV) and thus workload reduction (WR).MethodsRetrospective, observational cohort study in patients who underwent colorectal surgery from January 1, 2015, through September 30, 2020. NLP was used to detect keyword counts in clinical notes. Several NLP-algorithms were developed with different count input types and classifiers, and added as component to the original semi-automated algorithm. Traditional manual surveillance was compared with the NLP-augmented surveillance algorithms and sensitivity, specificity, PPV and WR were calculated.ResultsFrom the NLP-augmented models, the decision tree models with discretized counts or binary counts had the best performance (sensitivity 95.1% (95%CI 83.5-99.4%), WR 60.9%) and improved PPV and WR by only 2.6% and 3.6%, respectively, compared to the original algorithm.ConclusionsThe addition of an NLP component to the existing algorithm had modest effect on WR (decrease of 1.4-12.5%), at the cost of sensitivity. For future implementation it will be a trade-off between optimal case-finding techniques versus practical considerations such as acceptability and availability of resources.
  •  
40.
  • Wolff, Ellen, 1987, et al. (författare)
  • Cost-effectiveness of pneumococcal vaccination for elderly in Sweden
  • 2020
  • Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 38:32, s. 4988-4995
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The aim was to assess cost-effectiveness of including pneumococcal vaccination for elderly in a national vaccination programme in Sweden, comparing health-effects and costs of pneumococcal related diseases with a vaccination programme versus no vaccination. Method: We used a single-cohort deterministic decision-tree model to simulate the current burden of pneumococcal disease in Sweden. The model accounted for invasive pneumococcal disease (IPD) and pneumonia caused by pneumococci. Costs included in the analysis were those incurred when treating pneumococcal disease, and acquisition and administration of the vaccine. Health effects were measured as quality-adjusted life years (QALY). The time-horizon was set to five years, both effects and costs were discounted by 3% annually. Health-effects and costs were accumulated over the time-horizon and used to create an incremental cost-effectiveness ratio. The 23-valent polysaccharide vaccine (PPV23) was used in the base-case analysis. The 13-valent pneumococcal conjugate vaccine PCV13 was included in sensitivity analyses. Results: A vaccination programme using PPV23 would reduce the burden of pneumococcal related disease significantly, both when vaccinating a 65-year-old cohort and a 75-year-old cohort. IPD would decrease by 30% in the 65-year-old cohort, and by 29% in the 75-year-old cohort. The corresponding figures for CAP (communicable acquired pneumonia) are 19% and 15%. The cost per gained QALY was estimated to EUR 94,000 for vaccinating 65-year-olds and EUR 29,500 for 75-year-olds. With one dose PCV13 given instead of PPV23, the cost per gained QALY would increase by around 400% for both cohorts. The results were robust in sensitivity analyses. Conclusion: Introducing a vaccination programme against pneumococcal disease for 65-year-olds in Sweden is unlikely to be cost-effective, whereas it for 75 year-olds and using PPV23 can be considered good value for money. Our model indicates that vaccine price needs to be reduced by 55% for vaccination of 65-year-olds to be cost-effective, given a threshold of EUR 50,000. (C) 2020 Elsevier Ltd. All rights reserved.
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