A machine learning approach using endpoint adjudication committee labels for the identification of sepsis predictors at the emergency department.

Accurate sepsis diagnosis is paramount for treatment decisions, especially at the emergency department (ED). To improve diagnosis, clinical decision support (CDS) tools are being developed with machine learning (ML) algorithms, using a wide range of variable groups. ML models can find patterns in Electronic Health Record (EHR) data that are unseen by the human eye. A prerequisite for a good model is the use of high-quality labels. Sepsis gold-standard labels are hard to define due to a lack of reliable diagnostic tools for sepsis at the ED. Therefore, standard clinical tools, such as clinical prediction scores (e.g. modified early warning score and quick sequential organ failure assessment), and claims-based methods (e.g. ICD-10) are used to generate suboptimal labels. As a consequence, models trained with these "silver" labels result in ill-trained models. In this study, we trained ML models for sepsis diagnosis at the ED with labels of 375 ED visits assigned by an endpoint adjudication committee (EAC) that consisted of 18 independent experts. Our objective was to evaluate which routinely measured variables show diagnostic value for sepsis. We performed univariate testing and trained multiple ML models with 95 routinely measured variables of three variable groups; demographic and vital, laboratory and advanced haematological variables. Apart from known diagnostic variables, we identified added diagnostic value for less conventional variables such as eosinophil count and platelet distribution width. In this explorative study, we show that the use of an EAC together with ML can identify new targets for future sepsis diagnosis research.

Still New Chronic Q Fever Cases Diagnosed 8 Years After a Large Q Fever Outbreak.

BACKGROUND: Chronic Q fever usually develops within 2 years after primary infection with Coxiella burnetii. We determined the interval between acute Q fever and diagnosis of chronic infection, assessed what factors contribute to a longer interval, and evaluated the long-term follow-up. METHODS: From 2007 to 2018, patients with chronic Q fever were included from 45 participating hospitals. The interval between acute and chronic infection was calculated in patients with a known day of first symptoms and/or serological confirmation of acute Q fever. Chronic Q fever-related complications and mortality were assessed by 2 investigators based on predefined criteria. RESULTS: In total, 313 (60.3%) proven, 81 (15.6%) probable, and 125 (24.1%) possible chronic Q fever patients were identified. The date of acute Q fever was known in 200 patients: in 45 (22.5%), the interval was longer than 2 years, with the longest observed interval being 9.2 years. Patients in whom serological follow-up was performed after acute Q fever were diagnosed less often after this 2-year interval (odds ratio, 0.26; 95% confidence interval, 0.12-0.54). Chronic Q fever-related complications occurred in 216 patients (41.6%). Chronic Q fever-related mortality occurred in 83 (26.5%) of proven and 3 (3.7%) of probable chronic Q fever patients. CONCLUSIONS: Chronic Q fever is still being diagnosed and mortality keeps occurring 8 years after a large outbreak. Intervals between acute Q fever and diagnosis of chronic infection can reach more than 9 years. We urge physicians to perform microbiological testing for chronic Q fever even many years after an outbreak or acute Q fever disease.

Long-term serological follow-up after primary Coxiella burnetii infection in patients with vascular risk factors for chronic Q fever.

We evaluated the long-term serological follow-up of patients with vascular risk factors for chronic Q fever that were previously Coxiella burnetii seropositive. C. burnetii phase I IgG titers were reevaluated in patients that gave informed consent or retrospectively collected in patients already deceased or lost to follow-up. Of 107 patients, 25 (23.4%) became seronegative, 77 (72.0%) retained a profile of past resolved Q fever infection, and five (4.7%) developed chronic Q fever. We urge clinicians to stay vigilant for chronic Q fever beyond two years after primary infection and perform serological testing based on clinical presentation.

Differences in Documented and Actual Medication Administration Time in the Emergency Department: A Prospective, Observational, Time-Motion Study.

INTRODUCTION: Retrospective studies suggest that a rapid initiation of treatment results in a better prognosis for patients in the emergency department. There could be a difference between the actual medication administration time and the documented time in the electronic health record. In this study, the difference between the observed medication administration time and documentation time was investigated. Patient and nurse characteristics were also tested for associations with observed time differences. METHODS: In this prospective study, emergency nurses were followed by observers for a total of 3 months. Patient inclusion was divided over 2 time periods. The difference in the observed medication administration time and the corresponding electronic health record documentation time was measured. The association between patient/nurse characteristics and the difference in medication administration and documentation time was tested with a Spearman correlation or biserial correlation test. RESULTS: In 34 observed patients, the median difference in administration and documentation time was 6.0 minutes (interquartile range 2.0-16.0). In 9 (26.5%) patients, the actual time of medication administration differed more than 15 minutes with the electronic health record documentation time. High temperature, lower saturation, oxygen-dependency, and high Modified Early Warning Score were all correlated with an increasing difference between administration and documentation times. DISCUSSION: A difference between administration and documentation times of medication in the emergency department may be common, especially for more acute patients. This could bias, in part, previously reported time-to-treatment measurements from retrospective research designs, which should be kept in mind when outcomes of retrospective time-to-treatment studies are evaluated.

Cost-effectiveness of Screening Program for Chronic Q Fever, the Netherlands.

In the aftermath of a large Q fever (QF) epidemic in the Netherlands during 2007-2010, new chronic QF (CQF) patients continue to be detected. We developed a health-economic decision model to evaluate the cost-effectiveness of a 1-time screening program for CQF 7 years after the epidemic. The model was parameterized with spatial data on QF notifications for the Netherlands, prevalence data from targeted screening studies, and clinical data from the national QF database. The cost-effectiveness of screening varied substantially among subpopulations and geographic areas. Screening that focused on cardiovascular risk patients in areas with high QF incidence during the epidemic ranged from cost-saving to €31,373 per quality-adjusted life year gained, depending on the method to estimate the prevalence of CQF. The cost per quality-adjusted life year of mass screening of all older adults was €70,000 in the most optimistic scenario.

Rapid Molecular Tests for Influenza, Respiratory Syncytial Virus, and Other Respiratory Viruses: A Systematic Review of Diagnostic Accuracy and Clinical Impact Studies.

We systematically reviewed available evidence from Embase, Medline, and the Cochrane Library on diagnostic accuracy and clinical impact of commercially available rapid (results <3 hours) molecular diagnostics for respiratory viruses as compared to conventional molecular tests. Quality of included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies criteria for diagnostic test accuracy (DTA) studies, and the Cochrane Risk of Bias Assessment and Risk of Bias in Nonrandomized Studies of Interventions criteria for randomized and observational impact studies, respectively. Sixty-three DTA reports (56 studies) were meta-analyzed with a pooled sensitivity of 90.9% (95% confidence interval [CI], 88.7%-93.1%) and specificity of 96.1% (95% CI, 94.2%-97.9%) for the detection of either influenza virus (n = 29), respiratory syncytial virus (RSV) (n = 1), influenza virus and RSV (n = 19), or a viral panel including influenza virus and RSV (n = 14). The 15 included impact studies (5 randomized) were very heterogeneous and results were therefore inconclusive. However, we suggest that implementation of rapid diagnostics in hospital care settings should be considered.

External validation and update of a prognostic model to predict mortality in hospitalized adults with RSV: A retrospective Dutch cohort study.

Respiratory syncytial virus (RSV) causes significant mortality in hospitalized adults. Prediction of poor outcomes improves targeted management and clinical outcomes. We externally validated and updated existing models to predict poor outcome in hospitalized RSV-infected adults. In this single center, retrospective, observational cohort study, we included hospitalized adults with respiratory tract infections (RTIs) and a positive polymerase chain reaction for RSV (A/B) on respiratory tract samples (2005-2018). We validated existing prediction models and updated the best discriminating model by revision, recalibration, and incremental value testing. We included 192 RSV-infected patients (median age 60.7 years, 57% male, 65% immunocompromised, and 43% with lower RTI). Sixteen patients (8%) died within 30 days. During hospitalization, 16 (8%) died, 30 (16%) were admitted to intensive care unit, 21 (11%) needed invasive mechanical ventilation, and 5 (3%) noninvasive positive pressure ventilation. Existing models performed moderately at external validation, with C-statistics 0.6 to 0.7 and moderate calibration. Updating to a model including lower RTI, chronic pulmonary disease, temperature, confusion and urea, increased the C-statistic to 0.76 (95% confidence interval, 0.61-0.91) to predict in-hospital mortality. In conclusion, existing models to predict poor prognosis among hospitalized RSV-infected adults perform moderately at external validation. A prognostic model may help to identify and treat RSV-infected adults at high-risk of death.

Antibiotic misuse in respiratory tract infections in children and adults-a prospective, multicentre study (TAILORED Treatment).

Respiratory tract infections (RTI) are more commonly caused by viral pathogens in children than in adults. Surprisingly, little is known about antibiotic use in children as compared to adults with RTI. This prospective study aimed to determine antibiotic misuse in children and adults with RTI, using an expert panel reference standard, in order to prioritise the target age population for antibiotic stewardship interventions. We recruited children and adults who presented at the emergency department or were hospitalised with clinical presentation of RTI in The Netherlands and Israel. A panel of three experienced physicians adjudicated a reference standard diagnosis (i.e. bacterial or viral infection) for all the patients using all available clinical and laboratory information, including a 28-day follow-up assessment. The cohort included 284 children and 232 adults with RTI (median age, 1.3 years and 64.5 years, respectively). The proportion of viral infections was larger in children than in adults (209(74%) versus 89(38%), p < 0.001). In case of viral RTI, antibiotics were prescribed (i.e. overuse) less frequently in children than in adults (77/209 (37%) versus 74/89 (83%), p < 0.001). One (1%) child and three (2%) adults with bacterial infection were not treated with antibiotics (i.e. underuse); all were mild cases. This international, prospective study confirms major antibiotic overuse in patients with RTI. Viral infection is more common in children, but antibiotic overuse is more frequent in adults with viral RTI. Together, these findings support the need for effective interventions to decrease antibiotic overuse in RTI patients of all ages.

Cardiac events after macrolides or fluoroquinolones in patients hospitalized for community-acquired pneumonia: post-hoc analysis of a cluster-randomized trial.

BACKGROUND: Guidelines recommend macrolides and fluoroquinolones in patients hospitalized with community-acquired pneumonia (CAP), but their use has been associated with cardiac events. We quantified associations between macrolide and fluoroquinolone use and cardiac events in patients hospitalized with CAP in non-ICU wards. METHODS: This was a post-hoc analysis of a cluster-randomized trial as a cohort study; including patients with a working diagnosis of CAP admitted to non-ICU wards without a cardiac event on admission. We calculated cause-specific hazard ratio's (HR's) for effects of time-dependent macrolide and fluoroquinolone exposure as compared to beta-lactam monotherapy on cardiac events, defined as new or worsening heart failure, arrhythmia, or myocardial ischemia during hospitalization. RESULTS: Cardiac events occurred in 146 (6.9%) of 2107 patients, including heart failure (n = 101, 4.8%), arrhythmia (n = 53, 2.5%), and myocardial ischemia (n = 14, 0.7%). These occurred in 11 of 207 (5.3%), 18 of 250 (7.2%), and 31 of 277 (11.2%) patients exposed to azithromycin, clarithromycin, and erythromycin for at least one day, and in 9 of 234 (3.8%), 5 of 194 (2.6%), and 23 of 566 (4.1%) exposed to ciprofloxacin, levofloxacin, and moxifloxacin, respectively. HR's for erythromycin, compared to beta-lactam monotherapy, on any cardiac event and heart failure were 1.60 (95% CI 1.09;2.36) and 1.89 (95% CI 1.22;2.91), respectively. HR's for levofloxacin and moxifloxacin, compared to beta-lactam monotherapy, on any cardiac event were 0.40 (95% CI 0.18;0.87)and 0.56 (95% CI 0.36;0.87), respectively. Findings remained consistent after adjustment for confounders and/or in a sensitivity analysis of radiologically confirmed CAP (n = 1604, 76.1%). CONCLUSIONS: Among patients with CAP hospitalized to non-ICU wards, erythromycin use was associated with a 68% increased risk of hospital-acquired cardiac events, mainly heart failure. Levofloxacin and moxifloxacin were associated with a lower risk of heart failure. Although our study does not fully exclude confounding bias, findings remained largely unchanged in crude, adjusted, and sensitivity analyses. These findings may caution the use of erythromycin as empirical therapy in these patients. TRIAL REGISTRATION: The original trial was retrospectively registered under ClinicalTrials.gov Identifier NCT01660204 on August 8th, 2012.

Use of the moving epidemic method (MEM) to assess national surveillance data for respiratory syncytial virus (RSV) in the Netherlands, 2005 to 2017.

BackgroundTo control respiratory syncytial virus (RSV), which causes acute respiratory infections, data and methods to assess its epidemiology are important.AimWe sought to describe RSV seasonality, affected age groups and RSV-type distribution over 12 consecutive seasons in the Netherlands, as well as to validate the moving epidemic method (MEM) for monitoring RSV epidemics.MethodsWe used 2005-17 laboratory surveillance data and sentinel data. For RSV seasonality evaluation, epidemic thresholds (i) at 1.2% of the cumulative number of RSV-positive patients per season and (ii) at 20 detections per week (for laboratory data) were employed. We also assessed MEM thresholds.ResultsIn laboratory data RSV was reported 25,491 times (no denominator). In sentinel data 5.6% (767/13,577) of specimens tested RSV positive. Over 12 seasons, sentinel data showed percentage increases of RSV positive samples. The average epidemic length was 18.0 weeks (95% confidence intervals (CI): 16.3-19.7) and 16.5 weeks (95% CI: 14.0-18.0) for laboratory and sentinel data, respectively. Epidemics started on average in week 46 (95% CI: 45-48) and 47 (95% CI: 46-49), respectively. The peak was on average in the first week of January in both datasets. MEM showed similar results to the other methods. RSV incidence was highest in youngest (0-1 and >1-2 years) and oldest (>65-75 and > 75 years) age groups, with age distribution remaining stable over time. RSV-type dominance alternated every one or two seasons.ConclusionsOur findings provide baseline information for immunisation advisory groups. The possibility of employing MEM to monitor RSV epidemics allows prospective, nearly real-time use of surveillance data.

The prognostic value of red blood cell distribution width in patients with suspected infection in the emergency department.

BACKGROUND: Sepsis is a potential life threatening dysregulated immune response to an infection, which can result in multi-organ failure and death. Unfortunately, good prognostic markers are lacking in patients with suspected infection to identify those at risk. Red blood cell distribution width (RDW) is a common and inexpensive hematologic laboratory measurement associated with adverse prognosis in multiple diseases. The aim of this study was to determine the prognostic value of RDW for mortality and early clinical deterioration in patients with a suspected infection in the emergency department. METHODS: In this single center prospective observational cohort study, consecutive patients with suspected infection presenting for internal medicine in the emergency department between September 2016 and March 2018 were included. For prognostic validation of bedside sepsis scores and RDW receiver operating characteristics were generated. Association between RDW and mortality and ICU admission was analyzed univariate and in a multivariate logistic regression model. RESULTS: 1046 patients were included. In multivariate analyses, RDW was significantly associated with 30-day mortality (OR 1.15, 95% CI: 1.04-1.28) and early clinical deterioration (OR 1.09, 95% CI: 1.00-1.18). For 30-day mortality RDW had an AUROC of 0.66 (95% CI 0.59-0.72). Optimal cut-off value for RDW 2 was 12.95%. For early clinical deterioration RDW had an AUROC of 0.59 (95% CI 0.54-0.63) with an optimal cut-off value of 14.48%. CONCLUSIONS: RDW was found to be a significant independent prognostic factor of 30-day mortality and early clinical deterioration in patients with suspected infection.. Therefore it can be a used as an extra marker besides bedside sepsis scores in identifying patients at risk for worse outcome in patients with suspected infection.

Treatment of Chronic Q Fever: Clinical Efficacy and Toxicity of Antibiotic Regimens.

Background: Evidence on the effectiveness of first-line treatment for chronic Q fever, tetracyclines (TET) plus hydroxychloroquine (HCQ), and potential alternatives is scarce. Methods: We performed a retrospective, observational cohort study to assess efficacy of treatment with TET plus quinolones (QNL), TET plus QNL plus HCQ, QNL monotherapy, or TET monotherapy compared to TET plus HCQ in chronic Q fever patients. We used a time-dependent Cox proportional hazards model to assess our primary (all-cause mortality) and secondary outcomes (first disease-related event and therapy failure). Results: We assessed 322 chronic Q fever patients; 276 (86%) received antibiotics. Compared to TET plus HCQ (n = 254; 92%), treatment with TET plus QNL (n = 49; 17%), TET plus QNL plus HCQ (n = 29, 10%), QNL monotherapy (n = 93; 34%), or TET monotherapy (n = 54; 20%) were not associated with primary or secondary outcomes. QNL and TET monotherapies were frequently discontinued due to insufficient clinical response (n = 27, 29% and n = 32, 59%). TET plus HCQ, TET plus QNL, and TET plus QNL plus HCQ were most frequently discontinued due to side effects (n = 110, 43%; n = 13, 27%; and n = 12, 41%). Conclusions: Treatment of chronic Q fever with TET plus QNL appears to be a safe alternative for TET plus HCQ, for example, if TET plus HCQ cannot be tolerated due to side effects. Treatment with TET plus QNL plus HCQ was not superior to treatment with TET plus HCQ, although this may be caused by confounding by indication. Treatment with TET or QNL monotherapy should be avoided; switches due to subjective, insufficient clinical response were frequently observed.

Case report: Coxiella burnetii vascular infection and lymphoma in the Netherlands.

OBJECTIVES AND DESIGN: Non-Hodgkin lymphoma has been linked to infection with Coxiella burnetii, potentially through overproduction of IL-10 during infection with C. burnetii. MATERIALS AND METHODS: Description of a case report. RESULTS: We describe a patient with retroperitoneal non-Hodgkin lymphoma and vascular infection with C. burnetii. Immunofluorescence staining and fluorescence in situ hybridization targeting specific C. burnetii 16S rRNA were performed on the retroperitoneal lymphoma tissue sample obtained at diagnosis of NHL. Both were strongly positive for the presence of C. burnetii. CONCLUSIONS: This case provokes questions regarding a potential association between C. burnetii and NHL, and underlines the importance of further exploration of this association.

Seroprevalence of Coxiella burnetii antibodies and chronic Q fever among post-mortal and living donors of tissues and cells from 2010 to 2015 in the Netherlands.

BackgroundAfter a large Q fever outbreak in the Netherlands in the period from 2007 to 2010, the risk of Q fever transmission through tissue and cell transplantation from undiagnosed chronic Q fever cases became a potential issue. Aim: We aimed to evaluate the risk of Q fever transmission through tissue and cell transplantation. Methods: We performed a retrospective observational cohort study among 15,133 Dutch donors of tissues and stem cells from 2010 to 2015 to assess seroprevalence of Coxiella burnetii antibodies, to identify factors associated with presence of C. burnetii antibodies, and to assess the proportion of undiagnosed chronic Q fever cases. Results: The study population consisted of 9,478 (63%) femoral head donors, 5,090 (34%) post-mortal tissue donors and 565 (4%) cord blood donors. Seroprevalence of C. burnetii antibodies gradually decreased after the outbreak, from 2.1% in 2010 to 1.4% in 2015, with a significant trend in time (p < 0.001). Of 301 seropositive donors, seven (2.3%) were newly detected with chronic Q fever (0.05% of all screened donors). Conclusion: This study shows that seroprevalence of C. burnetii antibodies among donors of tissues and cells in the Netherlands after 2014 was similar to pre-outbreak levels in the general population. The proportion of newly detected chronic Q fever patients among donors of tissues and cells was smaller than 0.1%. This study may prompt discussion on when to terminate the screening programme for chronic Q fever in donors of tissues and cells in the Netherlands.

Community-acquired pneumonia requiring hospitalization: rational decision making and interpretation of guidelines.

PURPOSE OF REVIEW: This review focuses on the evidence base for guideline recommendations on the diagnosis, the optimal choice, timing and duration of empirical antibiotic therapy, and the use of microbiological tests for patients hospitalized with community-acquired pneumonia (CAP): issues for which guidelines are frequently used as a quick reference. Furthermore, we will discuss possibilities for future research in these topics. RECENT FINDINGS: Many national and international guideline recommendations, even on critical elements of CAP management, are based on low-to-moderate quality evidence. SUMMARY: The diagnosis and management of CAP has hardly changed for decades. The recommendation to cover atypical pathogens in all hospitalized CAP patients is based on observational studies only and is challenged by two recent trials. The following years, improved diagnostic testing, radiologically by low-dose Computed Tomography or ultrasound and/or microbiologically by point-of-care multiplex PCR, has the potential to largely influence the choice and start of antibiotic therapy in hospitalized CAP patients. Rapid microbiological testing will hopefully improve antibiotic de-escalation or early pathogen-directed therapy, both potent ways of reducing broad-spectrum antibiotic use. Current guideline recommendations on the timing and duration of antibiotic therapy are based on limited evidence, but will be hard to improve.

Cost-effectiveness of antibiotic treatment strategies for community-acquired pneumonia: results from a cluster randomized cross-over trial.

BACKGROUND: To determine the cost-effectiveness of strategies of preferred antibiotic treatment with beta-lactam/macrolide combination or fluoroquinolone monotherapy compared to beta-lactam monotherapy. METHODS: Costs and effects were estimated using data from a cluster-randomized cross-over trial of antibiotic treatment strategies, primarily from the reduced third payer perspective (i.e. hospital admission costs). Cost-minimization analysis (CMA) and cost-effectiveness analysis (CEA) were performed using linear mixed models. CMA results were expressed as difference in costs per patient. CEA results were expressed as incremental cost-effectiveness ratios (ICER) showing additional costs per prevented death. RESULTS: A total of 2,283 patients were included. Crude average costs within 90 days from the reduced third payer perspective were €4,294, €4,392, and €4,002 per patient for the beta-lactam monotherapy, beta-lactam/macrolide combination, and fluoroquinolone monotherapy strategy, respectively. CMA results were €106 (95% CI €-697 to €754) for the beta-lactam/macrolide combination strategy and €-278 (95%CI €-991 to €396) for the fluoroquinolone monotherapy strategy, both compared to the beta-lactam monotherapy strategy. The ICER was not statistically significantly different between the strategies. Other perspectives yielded similar results. CONCLUSIONS: There were no significant differences in cost-effectiveness of strategies of preferred antibiotic treatment of CAP on non-ICU wards with either beta-lactam monotherapy, beta-lactam/macrolide combination therapy, or fluoroquinolone monotherapy. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov, number NCT01660204 , on May 2nd, 2012.

Chronic Q fever diagnosis­ consensus guideline versus expert opinion

Chronic Q fever, caused by Coxiella burnetii, has high mortality and morbidity rates if left untreated. Controversy about the diagnosis of this complex disease has emerged recently. We applied the guideline from the Dutch Q Fever Consensus Group and a set of diagnostic criteria proposed by Didier Raoult to all 284 chronic Q fever patients included in the Dutch National Chronic Q Fever Database during 2006­2012. Of the patients who had proven cases of chronic Q fever by the Dutch guideline, 46 (30.5%)would not have received a diagnosis by the alternative criteria designed by Raoult, and 14 (4.9%) would have been considered to have possible chronic Q fever. Six patients with proven chronic Q fever died of related causes. Until results from future studies are available, by which current guidelines can be modified, we believe that the Dutch literature-based consensus guideline is more sensitive and easier to use in clinical practice.

Chronic Q fever in the Netherlands 5 years after the start of the Q fever epidemic: results from the Dutch chronic Q fever database.

Coxiella burnetii causes Q fever, a zoonosis, which has acute and chronic manifestations. From 2007 to 2010, the Netherlands experienced a large Q fever outbreak, which has offered a unique opportunity to analyze chronic Q fever cases. In an observational cohort study, baseline characteristics and clinical characteristics, as well as mortality, of patients with proven, probable, or possible chronic Q fever in the Netherlands, were analyzed. In total, 284 chronic Q fever patients were identified, of which 151 (53.7%) had proven, 64 (22.5%) probable, and 69 (24.3%) possible chronic Q fever. Among proven and probable chronic Q fever patients, vascular infection focus (56.7%) was more prevalent than endocarditis (34.9%). An acute Q fever episode was recalled by 27.0% of the patients. The all-cause mortality rate was 19.1%, while the chronic Q fever-related mortality rate was 13.0%, with mortality rates of 9.3% among endocarditis patients and 18% among patients with a vascular focus of infection. Increasing age (P=0.004 and 0.010), proven chronic Q fever (P=0.020 and 0.002), vascular chronic Q fever (P=0.024 and 0.005), acute presentation with chronic Q fever (P=0.002 and P<0.001), and surgical treatment of chronic Q fever (P=0.025 and P<0.001) were significantly associated with all-cause mortality and chronic Q fever-related mortality, respectively.

Potential impact of a new sepsis prediction model for the primary care setting: early health economic evaluation using an observational cohort.

OBJECTIVES: To estimate the potential referral rate and cost impact at different cut-off points of a recently developed sepsis prediction model for general practitioners (GPs). DESIGN: Prospective observational study with decision tree modelling. SETTING: Four out-of-hours GP services in the Netherlands. PARTICIPANTS: 357 acutely ill adult patients assessed during home visits. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is the cost per patient from a healthcare perspective in four scenarios based on different cut-off points for referral of the sepsis prediction model. Second, the number of hospital referrals for the different scenarios is estimated. The potential impact of referral of patients with sepsis on mortality and hospital admission was estimated by an expert panel. Using these study data, a decision tree with a time horizon of 1 month was built to estimate the referral rate and cost impact in case the model would be implemented. RESULTS: Referral rates at a low cut-off (score 2 or 3 on a scale from 0 to 6) of the prediction model were higher than observed for patients with sepsis (99% and 91%, respectively, compared with 88% observed). However, referral was also substantially higher for patients who did not need hospital assessment. As a consequence, cost-savings due to referral of patients with sepsis were offset by increased costs due to unnecessary referral for all cut-offs of the prediction model. CONCLUSIONS: Guidance for referral of adult patients with suspected sepsis in the primary care setting using any cut-off point of the sepsis prediction model is not likely to save costs. The model should only be incorporated in sepsis guidelines for GPs if improvement of care can be demonstrated in an implementation study. TRIAL REGISTRATION NUMBER: Dutch Trial Register (NTR 7026).

Delayed diagnosis of chronic Q fever and cardiac valve surgery.

Untreated chronic Q fever causes a high number of complications and deaths. We present cases of chronic Q fever that were not diagnosed until after the patients underwent cardiac valve surgery. In epidemic areas, Q fever screening of valve surgery patients secures early initiation of treatment and can prevent illness and death.