Reliability and Accuracy of the Pediatric Swiss Emergency Triage Scale-the SETSped Study.

BACKGROUND AND IMPORTANCE: The Swiss Emergency Triage Scale (SETS) is an adult triage tool used in several emergency departments. It has been recently adapted to the pediatric population but, before advocating for its use, performance assessment of this tool is needed. OBJECTIVES: The purpose of this study was to assess the reliability and the accuracy of the pediatric version of the SETS for the triage of pediatric patients. DESIGN, SETTING, AND PARTICIPANTS: This study was a cross-sectional study among a sample of emergency triage nurses (ETNs) exposed to 17 clinical scenarios using a computerized simulator. OUTCOME MEASURES AND ANALYSIS: The primary outcome was the reliability of the triage level performed by the ETNs. It was assessed using an intraclass correlation coefficient.Secondary outcomes included accuracy of triage compared with expert-based triage levels and factors associated with accurate triage. MAIN RESULTS: Eighteen ETNs participated in the study and completed the evaluation of all scenarios, for a total of 306 triage decisions. The intraclass correlation coefficient was 0.80 (95% confidence interval, 0.69-0.91), with an agreement by scenario ranging from 61.1% to 100%. The overall accuracy was 85.8%, and nurses were more likely to undertriage (16.0%) than to overtriage (4.3%). No factor for accurate triage was identified. CONCLUSIONS: This simulator-based study showed that the SETS is reliable and accurate among a pediatric population. Future research is needed to confirm these results, compare this triage scale head-to-head with other recognized international tools, and study the SETSped in real-life setting.

Longitudinal profile of estrogen-related thrombotic biomarkers after cessation of combined hormonal contraceptives.

ABSTRACT: The persistence of risk of venous thromboembolism (VTE) due to combined hormonal contraceptives (CHCs), after their cessation, is unknown but important to guide clinical practice. The objective of this prospective cohort study was to define the time until normalization of estrogen-related thrombotic biomarkers after CHC cessation. We enrolled women aged 18 to 50 years who had decided to stop their CHC, excluding those with a personal history of VTE, anticoagulation, or pregnancy. The study started before cessation of CHC, with 6 visits afterwards (at 1, 2, 4, 6, and 12 weeks after cessation). Primary outcomes were normalized sensitivity ratios to activated protein C (nAPCsr) and to thrombomodulin (nTMsr), with sex hormone-binding globulin (SHBG) as a secondary end point. We also included control women without CHC. Among 66 CHC users, from baseline until 12 weeks, average levels of nAPCsr, nTMsr, and SHBG decreased from 4.11 (standard deviation [SD], 2.06), 2.53 (SD, 1.03), and 167 nmol/L (SD, 103) to 1.27 (SD, 0.82), 1.11 (SD, 0.58), and 55.4 nmol/L (SD, 26.7), respectively. On a relative scale, 85.8%, 81.3%, and 76.2% of the decrease from baseline until 12 weeks was achieved at 2 weeks and 86.7%, 85.5%, and 87.8% at 4 weeks after CHC cessation, respectively. Levels were not meaningfully modified throughout the study period among 28 control women. In conclusion, CHC cessation is followed by a rapid decrease in estrogen-related thrombotic biomarkers. Two to 4 weeks of cessation before planned major surgery or withdrawal of anticoagulants in patients with VTE appears sufficient for the majority of women. The trial is registered at www.clinicaltrials.gov as #NCT03949985.

Longitudinal Detection of Twenty DNA and RNA Viruses in Allogeneic Hematopoietic Stem Cell Transplant Recipients Plasma.

Metagenomics revealed novel and routinely overlooked viruses, representing sources of unrecognized infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aim to describe DNA and RNA virus prevalence and kinetics in allo-HSCT recipients' plasma for one year post HSCT. We included 109 adult patients with first allo-HSCT from 1 March 2017 to 31 January 2019 in this observational cohort study. Seventeen DNA and three RNA viral species were screened with qualitative and/or quantitative r(RT)-PCR assays using plasma samples collected at 0, 1, 3, 6, and 12 months post HSCT. TTV infected 97% of patients, followed by HPgV-1 (prevalence: 26-36%). TTV (median 3.29 × 105 copies/mL) and HPgV-1 (median 1.18 × 106 copies/mL) viral loads peaked at month 3. At least one Polyomaviridae virus (BKPyV, JCPyV, MCPyV, HPyV6/7) was detected in >10% of patients. HPyV6 and HPyV7 prevalence reached 27% and 12% at month 3; CMV prevalence reached 27%. HSV, VZV, EBV, HHV-7, HAdV and B19V prevalence remained <5%. HPyV9, TSPyV, HBoV, EV and HPg-V2 were never detected. At month 3, 72% of patients had co-infections. TTV and HPgV-1 infections were highly prevalent. BKPyV, MCPyV and HPyV6/7 were frequently detected relative to classical culprits. Further investigation is needed into associations between these viral infections and immune reconstitution or clinical outcomes.

Limitation of life-sustaining therapies in critically ill patients with COVID-19: a descriptive epidemiological investigation from the COVID-ICU study.

BACKGROUND: Limitations of life-sustaining therapies (LST) practices are frequent and vary among intensive care units (ICUs). However, scarce data were available during the COVID-19 pandemic when ICUs were under intense pressure. We aimed to investigate the prevalence, cumulative incidence, timing, modalities, and factors associated with LST decisions in critically ill COVID-19 patients. METHODS: We did an ancillary analysis of the European multicentre COVID-ICU study, which collected data from 163 ICUs in France, Belgium and Switzerland. ICU load, a parameter reflecting stress on ICU capacities, was calculated at the patient level using daily ICU bed occupancy data from official country epidemiological reports. Mixed effects logistic regression was used to assess the association of variables with LST limitation decisions. RESULTS: Among 4671 severe COVID-19 patients admitted from February 25 to May 4, 2020, the prevalence of in-ICU LST limitations was 14.5%, with a nearly six-fold variability between centres. Overall 28-day cumulative incidence of LST limitations was 12.4%, which occurred at a median of 8 days (3-21). Median ICU load at the patient level was 126%. Age, clinical frailty scale score, and respiratory severity were associated with LST limitations, while ICU load was not. In-ICU death occurred in 74% and 95% of patients, respectively, after LST withholding and withdrawal, while median survival time was 3 days (1-11) after LST limitations. CONCLUSIONS: In this study, LST limitations frequently preceded death, with a major impact on time of death. In contrast to ICU load, older age, frailty, and the severity of respiratory failure during the first 24 h were the main factors associated with decisions of LST limitations.

Prothrombotic biomarkers during controlled ovarian stimulation for assisted reproductive technology.

OBJECTIVE: To assess the impact of 3 different ovarian stimulation protocols on surrogate biomarkers of coagulation. DESIGN: Observational multicenter cohort study. SETTING: The study was conducted in assisted reproductive technology (ART) units. PATIENTS: Infertile women undergoing ART in 2017-2019 were included. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Our primary outcome was the endogenous thrombin potential (ETP) assessed by the calibrated automated thrombogram. The ETP was measured at baseline (T1), on the day of ovulation triggering (T2), and 7 days after triggering (T3). Three protocols were prescribed according to the standards used and without hormonal before treatment: agonist protocol with human chorionic gonadotropin (hCG) trigger (ag-hCG), antagonist protocol with hCG trigger (atg-hCG), or GnRH agonist trigger. The evolution of ETP was compared among groups using a mixed-effects linear regression model. RESULT(S): Sixty-four women with a mean age of 37.8 years participated in the study: of which 24, 16, 24 received ag-hCG, atg-hCG, and GnRH agonist triggers, respectively. As expected, the mean serum estradiol levels in GnRH agonist trigger were statistically higher at T2 and lower at T3 than that for both ag-hCG and atg-hCG. Overall, the ETP evolution over time was statistically different between the groups. Values were similar between groups at T1 and increased at T2 in each group. The greatest difference occurred between T2 and T3 in each group. The ETP continued to increase at T3 in ag-hCG (+110 nM/L × min) and atg-hCG (+171 nM/L × min), but it remained stable in GnRH agonist trigger (-2 nM/L × min). Sex hormone-binding globulin showed persistent increase at T3 despite the fall in estradiol levels, particularly in the GnRH agonist trigger group. CONCLUSION(S): The ag-hCG and atg-hCG groups were associated with a higher hypercoagulable state at T3 than the GnRH agonist trigger group. However, our results show the persistence of a hypercoagulable state after the GnRH agonist triggering despite a sharp drop in estradiol levels. These findings may support the use of GnRH agonist trigger protocol in patients with high thrombotic risk and gives new insight into the fact that coagulation parameters could be disturbed for long time periods. CLINICAL TRIAL REGISTRATION NUMBER: NCT04188444.

Adjustment for baseline characteristics in randomized trials using logistic regression: sample-based model versus true model.

BACKGROUND: Adjustment for baseline prognostic factors in randomized clinical trials is usually performed by means of sample-based regression models. Sample-based models may be incorrect due to overfitting. To assess whether overfitting is a problem in practice, we used simulated data to examine the performance of the sample-based model in comparison to a "true" adjustment model, in terms of estimation of the treatment effect. METHODS: We conducted a simulation study using samples drawn from a "population" in which both the treatment effect and the effect of the potential confounder were specified. The outcome variable was binary. Using logistic regression, we compared three estimates of the treatment effect in each situation: unadjusted, adjusted for the confounder using the sample, adjusted for the confounder using the true effect. Experimental factors were sample size (from 2 × 50 to 2 × 1000), treatment effect (logit of 0, 0.5, or 1.0), confounder type (continuous or binary), and confounder effect (logit of 0, - 0.5, or - 1.0). The assessment criteria for the estimated treatment effect were bias, variance, precision (proportion of estimates within 0.1 logit units), type 1 error, and power. RESULTS: Sample-based adjustment models yielded more biased estimates of the treatment effect than adjustment models that used the true confounder effect but had similar variance, accuracy, power, and type 1 error rates. The simulation also confirmed the conservative bias of unadjusted analyses due to the non-collapsibility of the odds ratio, the smaller variance of unadjusted estimates, and the bias of the odds ratio away from the null hypothesis in small datasets. CONCLUSIONS: Sample-based adjustment yields similar results to exact adjustment in estimating the treatment effect. Sample-based adjustment is preferable to no adjustment.

Early urine output monitoring in very preterm infants to predict in-hospital neonatal outcomes: a bicentric retrospective cohort study.

OBJECTIVE: To evaluate whether urine output (UO), rarely assessed in the literature, is associated with relevant neonatal outcomes in very preterm infants, and which UO threshold may be the most clinically relevant. DESIGN: Retrospective cohort study. SETTING: Two Level IV neonatal intensive care units. PATIENTS: Very preterm infants born between 240/7 and 296/7 weeks of gestation documented with eight UO measurements per day between postnatal day 1 and day 7. MAIN OUTCOME MEASURES: Composite outcome defined as death before discharge, or moderate to severe bronchopulmonary dysplasia, or severe brain lesions. The association between this outcome and UO was studied using several UO thresholds. RESULTS: Among 532 infants studied, UO <1.0 mL/kg/hour for at least 24 consecutive hours was measured in 55/532 (10%) infants and the primary outcome was recorded in 25 patients. The association between a UO threshold <1.0 mL/kg/hour and the primary outcome was found marginally significant (crude OR 1.80, 95% CI 1.02 to 3.16, p=0.04). The primary outcome was recorded in 112/242 (46%) patients with a UO <2.0 mL/kg/hour and only 64/290 (22%) patients with a UO ≥2.0 mL/kg/hour (p<0.001). This UO threshold was found significantly associated with the primary outcome (crude OR 3.1, 95% CI 2.1 to 4.7, p<0.001), an association confirmed using a multivariate logistic regression model including baseline covariates (adjusted OR 3.7, 95% CI 2.2 to 6.4, p<0.001). CONCLUSION: A UO <2 mL/kg/hour over 24 hours between postnatal day 1 and day 7 strongly predicts neonatal mortality or severe morbidities in very preterm infants.

Detection of distant metastases and distant second primary cancers in head and neck squamous cell carcinoma: comparison of [18F]FDG PET/MRI and [18F]FDG PET/CT.

PURPOSE: This prospective study aimed to compare the diagnostic performance of [18]FDG PET/MRI and PET/CT for the detection of distant metastases and distant second primary cancers in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 103 [18F]FDG PET/MRI examinations immediately followed by PET/CT were obtained in 82 consecutive patients for staging of primary HNSCC (n = 38), suspected loco-regional recurrence/follow-up (n = 41) or unknown primary HNSCC (n = 3). Histology and follow-up > 2 years formed the standard of reference. Blinded readers evaluated the anonymized PET/MRI and PET/CT examinations separately using a 5-point Likert score. Statistical analysis included: receiver operating characteristic (ROC) analysis, jackknife alternative free-response ROC (JAFROC) and region-of-interest (ROI)-based ROC to account for data clustering and sensitivity/specificity/accuracy comparisons for a score ≥ 3. RESULTS: Distant metastases and distant second primary cancers were present in 23/103 (22%) examinations in 16/82 (19.5%) patients, and they were more common in the post-treatment group (11/41, 27%) than in the primary HNSCC group (3/38, 8%), p = 0.039. The area under the curve (AUC) per patient/examination/lesion was 0.947 [0.927-1]/0.965 [0.917-1]/0.957 [0.928-0.987] for PET/MRI and 0.975 [0.950-1]/0.968 [0.920-1]/0.944 [0.910-0.979] for PET/CT, respectively (p > 0.05). The diagnostic performance of PET/MRI and PET/CT was similar according to JAFROC (p = 0.919) and ROI-based ROC analysis (p = 0.574). Sensitivity/specificity/accuracy for PET/MRI and PET/CT for a score ≥ 3 was 94%/88%/89% and 94%/91%/91% per patient, 96%/90%/91% and 96%/93%/93% per examination and 95%/85%/90% and 90%/86%/88% per lesion, respectively, p > 0.05. CONCLUSIONS: In HNSCC patients, PET/MRI and PET/CT had a high and similar diagnostic performance for detecting distant metastases and distant second primary cancers.

Limping and patient satisfaction after primary total hip arthroplasty: a registry-based cohort study.

BACKGROUND AND PURPOSE: The influence of postoperative limping on patient satisfaction and amount of limping reduction following THA are not well documented. We (1) assessed if postoperative limping is associated with satisfaction 5 years after THA performed via the lateral or anterior approach; (2) evaluated the influence of surgical approach on amount of limping reduction following THA. PATIENTS AND METHODS: We conducted a prospective cohort study of primary elective THAs performed in 2002-2013. Limping was assessed before and 5 years after surgery using the Harris Hip limping sub-score. Satisfaction was assessed at 5 years on a 5-point Likert scale. We compared proportions of satisfied patients among groups of limping. Evolution of limping before and after surgery was noted. Analyses were performed overall and stratified by pain and surgical approach. We used univariate and multivariate logbinomial regression models. RESULTS: 1,257 patients were included (mean age 70 years). 81% had surgery via a lateral and 19% via an anterior approach. Before THA, 60% had moderate to severe limping and all reported pain. After THA, limping and pain improved; 9% of patients were dissatisfied. In multivariate analysis stratified on pain level, limping was associated with higher dissatisfaction. Similar results were obtained after lateral vs. anterior approach. INTERPRETATION: Postoperative limping impacts patient satisfaction after THA. The association varied by degree of limping and absence or presence of pain. It was independent of surgical approach. 5 years after THA occurrence of limping was largely reduced after both a lateral and an anterior approach, with low evidence of a greater reduction under an anterior approach.

Urine Output Monitoring for the Diagnosis of Early-Onset Acute Kidney Injury in Very Preterm Infants.

BACKGROUND AND OBJECTIVES: The current threshold used for oliguria in the definition of neonatal AKI has been empirically defined as 1 ml/kg per hour. Urine output criteria are generally poorly documented, resulting in uncertainty in the most accurate threshold to identify AKI in very preterm infants with known tubular immaturity. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a bicentric study including 473 very preterm infants (240/7-296/7 weeks of gestation) born between January 2014 and December 2018 with urine output measurements every 3 hours during the first 7 days of life and two serum creatinine measurements during the first 10 days of life. AKI was defined using the neonatal Kidney Disease Improving Global Outcomes (KDIGO) definition. We tested whether higher urine output thresholds (1.5 or 2 ml/kg per hour) in modified AKI definitions may better discriminate neonatal mortality compared with the current definition. RESULTS: Early-onset AKI was developed by 101 of 473 (21%) very preterm infants. AKI was diagnosed on the basis of urine output criteria alone (no rise in creatinine) for 27 of 101 (27%) participants. Early-onset AKI was associated with higher risk of death before discharge (adjusted odds ratio, 3.9; 95% confidence interval, 1.9 to 7.8), and the AKI neonatal KDIGO score showed good discriminative performance for neonatal mortality, with an area under the receiver operating characteristic (ROC) curve of 0.68 (95% confidence interval, 0.61 to 0.75). Modified AKI definitions that included higher urine output thresholds showed significantly improved discriminative performance, with areas under the ROC curve of 0.73 (95% confidence interval, 0.66 to 0.80) for the 1.5-ml/kg per hour threshold and 0.75 (95% confidence interval, 0.68 to 0.81) for the 2-ml/kg per hour threshold. CONCLUSIONS: Early-onset AKI was diagnosed on the basis of urine output exclusively for a quarter of the cases. Furthermore, modified AKI definitions that included higher urine output improved the discriminative performance for predicting mortality.

Invasive Mold Infections in Allogeneic Hematopoietic Cell Transplant Recipients in 2020: Have We Made Enough Progress?

BACKGROUND: Despite progress in diagnostic, prevention, and treatment strategies, invasive mold infections (IMIs) remain the leading cause of mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients. METHODS: We describe the incidence, risk factors, and mortality of allo-HCT recipients with proven/probable IMI in a retrospective single-center 10-year (01/01/2010-01/01/2020) cohort study. RESULTS: Among 515 allo-HCT recipients, 48 (9.3%) patients developed 51 proven/probable IMI: invasive aspergillosis (IA; 34/51, 67%), mucormycosis (9/51, 18%), and other molds (8/51, 15%). Overall, 35/51 (68.6%) breakthrough IMIs (bIMIs) were identified: 22/35 (62.8%) IA and 13/35 (37.1%) non-IA IMI. One-year IMI cumulative incidence was 7%: 4.9% and 2.1% for IA and non-IA IMI, respectively. Fourteen (29.2 %), 10 (20.8%), and 24 (50.0%) patients were diagnosed during the first 30, 31-180, and >180 days post-HCT, respectively. Risk factors for IMI included prior allo-HCT (sub hazard ratio [SHR], 4.06; P = .004) and grade ≥2 acute graft-vs-host disease (aGvHD; SHR, 3.52; P < .001). All-cause 1-year mortality was 33% (170/515): 48% (23/48) and 31.5% (147/467) for patients with and without IMI (P = .02). Mortality predictors included disease relapse (hazard ratio [HR], 7.47; P < .001), aGvHD (HR, 1.51; P = .001), CMV serology-positive recipients (HR, 1.47; P = .03), and IMI (HR, 3.94; P < .001). All-cause 12-week mortality for patients with IMI was 35.4% (17/48): 31.3% (10/32) for IA and 43.8% (7/16) for non-IA IMI (log-rank P = .47). At 1 year post-IMI diagnosis, 70.8% (34/48) of the patients were dead. CONCLUSIONS: IA mortality has remained relatively unchanged during the last 2 decades. More than two-thirds of allo-HCT recipients with IMI die by 1 year post-IMI diagnosis. Dedicated intensified research efforts are required to further improve clinical outcomes.

Nontuberculous Mycobacteria under Scrutiny in the Geneva Area (2015-2020).

BACKGROUND: Nontuberculous mycobacteria (NTM) are increasingly identified in industrialized countries, and their role as pathogens is more frequently recognized. The relative prevalence of NTM strains shows an important geographical variability. Thus, establishing the local relative prevalence of NTM strains is relevant and useful for clinicians. METHODS: Retrospective analysis (2015-2020) of a comprehensive database was conducted including all results of cultures for mycobacteria in a University Hospital (Geneva, Switzerland), covering a population of approximately 500,000 inhabitants. All NTM culture-positive patients were included in the analyses. Patients' characteristics, NTM strains, and time to culture positivity were reported. RESULTS: Among 38,065 samples analyzed during the study period, 411 were culture-positive for NTM, representing 236 strains, and 231 episodes of care which occurred in 222 patients. Patients in whom NTM were identified were predominantly female (55%), with a median age of 62 years, and a low BMI (median: 22.6 kg/m2). The Mycobacterium avium complex (MAC) was the most frequently identified group (37% of strains) followed by Mycobacterium gordonae (25%) and Mycobacterium xenopi (12%) among the slowly growing mycobacteria (SGM), while the Mycobacterium chelonae/abscessus group (11%) were the most frequently identified rapidly growing mycobacteria (RGM). Only 19% of all patients were treated, mostly for pulmonary infections: the MAC was the most frequently treated NTM (n = 19, 43% of cases in patients treated) followed by RGM (n = 15, 34%) and M. xenopi (n = 6, 14%). Among those treated, 23% were immunosuppressed, 12% had pulmonary comorbidities, and 5% systemic comorbidities. Cultures became positive after a median of 41 days (IQR: 23; 68) for SGM and 28 days (14; 35) for RGM. CONCLUSIONS: In Western Switzerland, M. avium and M. gordonae were the most prevalent NTM identified. Positive cultures for NTM led to a specific treatment in 19% of subjects. Patients with a positive culture for NTM were mostly female, with a median age of 62 years, a low BMI, and a low prevalence of immunosuppression or associated severe comorbidities.

Symptoms and quality of life at 1-year follow up of patients discharged after an acute COVID-19 episode.

AIM OF THE STUDY: Patients surviving COVID-19 have been described as being at risk of developing sequelae. We aimed to investigate and elicit persistent symptoms, emotional status and quality-of-life in patients discharged after an acute COVID-19 episode. METHODS: Patient-reported outcome measures were collected during a telephone interview 30 days and 1 year after discharge. Patients' general health status was evaluated using questions based on their symptoms, emotional status was assessed using the items 9 to 12 of the HeartQoL questionnaire and quality of life was assessed at 1 year through the EQ-5D-5L. In patients with a history of cardiovascular disease, all 14 items of the HeartQoL questionnaire were completed to derive the HeartQoL global score. RESULTS: Among 687 patients who survived after being hospitalised for COVID-19 at the University Hospitals of Geneva between 26 February and 26 April 2020, 184 (27%) and 165 (24%), respectively, participated in the follow-up at 30 days and 1 year. Of these 184 participants, 62% were male, median age was 58 years and 21% had a past medical history of cardiovascular disease. At one month after discharge, 61% (113/184) of patients presented fatigue and 28% (52/184) dyspnoea. One year after discharge, the main complaints were persistent fatigue in 27% (45/165) of patients, neurological problems in 17% (28/165) and dyspnoea in 14% (23/165). Eight percent (14/184) of patients declared being significantly worried 1 month after discharge and 5% (9/184) feeling depressed. The number of patients reporting being significantly worried or depressed at 1 year was lower. Regarding the quality of life at 1 year, the median EQ-5D-5L visual analogue scale score was 80 (interquartile range 70-90). CONCLUSIONS: Approximately half of patients reported some symptoms 1 year after discharge following an acute episode of COVID-19. The predominant symptom was persistent fatigue both at 1-month and at 1-year follow-up. Emotional status and quality of life appeared satisfactory.

Time to Detection of Growth for Mycobacterium tuberculosis in a Low Incidence Area.

Background: Diagnosis of Mycobacterium tuberculosis (MTB) infection can be confirmed by Xpert assays within hours. However, when sample size does not allow performing both culture and Xpert, or if Xpert is negative, then formal diagnosis of MTB relies on culture and time to detection of growth (TDG) becomes critical for clinical management. Objectives: To determine TDG in Xpert negative samples, or in samples in which Xpert could not be performed, in a low-incidence area for MTB. Methods: Retrospective analysis (2015-2020) of a database including all cultures for mycobacteria in a University Hospital covering approximately 500'000 inhabitants. Analysis was restricted to culture positive (C+) samples for MTB for which 1/Xpert was negative or could not be performed because of limited sample volume, and 2/collected from subjects treated less than 24 hours. TDG was analyzed according to microscopy, origin of sample (pulmonary or not) and presence of cavitation. Results: Among 837 C+ samples for MTB, 236 samples (80% of respiratory origin) from 147 patients fulfilled study criteria; 78 samples (49 patients, 33%) were acid-fast bacilli (AFB) positive. Median (IQR) TDG was 25 (17; 40) days for all samples. TDG exceeded 28 days in 43% of samples and was significantly shorter in AFB+ vs AFB- samples, and samples from cavitary vs non cavitary or extra-thoracic disease. Conclusions: In Xpert negative samples, or samples for which Xpert could not be performed, TDG exceeded 4 weeks in 43% of samples. AFB+ and samples from cavitary lung disease had a significantly shorter TDG.

Inter- and intraobserver reliability assessment of the 2018 AO/OTA classification for high-energy pelvic ring injuries: A retrospective study.

BACKGROUND: A fracture classification system should be a reliable and reproducible means of communication between different observers. It should be logical, comprehensible, and shouldn't contain an unmanageable number of categories. The aim of this study was to assess the intra- and interobserver agreement and reliability of the revised 2018 AO/OTA classification for high-energy pelvic ring injuries (PRI), at the level of the types, groups, subgroups and qualifications. HYPOTHESIS: Agreement and reliability of the revised 2018 AO/OTA classification for high-energy PRI are improved when compared to previous versions of the classification. PATIENTS AND METHODS: Plain radiographs and computed tomography images of a consecutive series of 86 adult patients admitted at a level I trauma center with a high-energy PRI between 01.01.2014 and 31.12.2016 were retrospectively analyzed. Three orthopedic surgeons independently classified these PRI using the 2018 AO/OTA and the Young and Burgess classifications. The senior surgeon analyzed all injuries twice, at 6 months interval, to determine intraobserver reliability. Classification agreement was assessed using percent agreement and classification reliability was assessed using kappa coefficients. RESULTS: For the intraobserver analysis, injury classifications with the 2018 AO/OTA classification were concordant in 88% of cases (type), 74% (group), 66% (subgroup) and 49% (qualification). Respective kappa coefficients were 0.79, 0.68, 0.62 and 0.47. Interobserver agreement declined from 77% (type) to 42% (group), 36% (subgroup) and 24% (qualification). Respective kappa coefficients were 0.72, 0.48, 0.48 and 0.37. Intraobserver (respectively interobserver) percent agreement with the Young and Burgess classification was 76% (50%) and kappa coefficient was 0.69 (0.51). DISCUSSION: The 2018 AO/OTA classification is a reliable tool for daily clinical use and for research purpose at the fracture type level but not at the group, subgroup and qualification levels. These results compare favorably with previously published data for older versions of the classification and may represent an improvement of the AO/OTA classification system in terms of reliability. LEVEL OF EVIDENCE: III; retrospective diagnostic study.

Longitudinal Timed Up and Go Assessment in Amyotrophic Lateral Sclerosis: A Pilot Study.

Progressive loss of walking ability in amyotrophic lateral sclerosis (ALS) has been scarcely studied as a potential predictive factor for survival in motor neuron disease. We aimed to assess the progression of gait decline and its association with mortality in ALS using the Timed Up and Go test (TUG). Patients were followed up prospectively at the Centre for ALS and Related Disorders in Geneva University Hospitals between 2012 and 2016. The TUG was performed at baseline and subsequent evaluations occurred every 3 months. At inclusion, patients were classified as unable to perform the TUG, "slow TUG" (>10.6 s), and "fast TUG" (≤10.6 s). In total, 68 patients with ALS (mean ± SD age: 68.6 ± 11.9 years; 50% female) were included. Baseline TUG was negatively correlated with the total ALSFRS-R score (r = -0.63, p < 0.001). At baseline, ALS patients with bulbar onset performed the TUG faster (9.9 ± 3.7 s) than the non-bulbar ones (17.3 ± 14.9 s, p = 0.008). Thirty of 68 (44%) patients died by the end of the follow-up period. The TUG performance at the first visit did not predict mortality. While we did not find any association with mortality in ALS and gait quantification, the TUG was feasible in a majority of ALS patients, was correlated with functional status, and could be of interest in the follow-up of non-bulbar ALS patients.

Mortality and high risk of major adverse events in patients with COVID-19 and history of cardiovascular disease.

OBJECTIVE: History of cardiovascular diseases (CVDs) may influence the prognosis of patients hospitalised for COVID-19. We investigated whether patients with previous CVD have increased risk of death and major adverse cardiovascular event (MACE) when hospitalised for COVID-19. METHODS: We included 839 patients with COVID-19 hospitalised at the University Hospitals of Geneva. Demographic characteristics, medical history, laboratory values, ECG at admission and medications at admission were collected based on electronic medical records. The primary outcome was a composite of in-hospital mortality or MACE. RESULTS: Median age was 67 years, 453 (54%) were males and 277 (33%) had history of CVD. In total, 152 (18%) died and 687 (82%) were discharged, including 72 (9%) who survived a MACE. Patients with previous CVD were more at risk of composite outcomes 141/277 (51%) compared with those without CVD 83/562 (15%) (OR=6.0 (95% CI 4.3 to 8.4), p<0.001). Multivariate analyses showed that history of CVD remained an independent risk factor of in-hospital death or MACE (OR=2.4; (95% CI 1.6 to 3.5)), as did age (OR for a 10-year increase=2.2 (95% CI 1.9 to 2.6)), male gender (OR=1.6 (95% CI 1.1 to 2.3)), chronic obstructive pulmonary disease (OR=2.1 (95% CI 1.0 to 4.2)) and lung infiltration associated with COVID-19 at CT scan (OR=1.9 (95% CI 1.2 to 3.0)). History of CVD (OR=2.9 (95% CI 1.7 to 5)), age (OR=2.5 (95% CI 2.0 to 3.2)), male gender (OR=1.6 (95% CI 0.98 to 2.6)) and elevated C reactive protein (CRP) levels on admission (OR for a 10 mg/L increase=1.1 (95% CI 1.1 to 1.2)) were independent risk factors for mortality. CONCLUSION: History of CVD is associated with higher in-hospital mortality and MACE in hospitalised patients with COVID-19. Other factors associated with higher in-hospital mortality are older age, male sex and elevated CRP on admission.

Rapid Sequence Induction With a Standard Intubation Dose of Rocuronium After Magnesium Pretreatment Compared With Succinylcholine: A Randomized Clinical Trial.

BACKGROUND: Succinylcholine remains the muscle relaxant of choice for rapid sequence induction (RSI) but has many adverse effects. High-dose rocuronium bromide may be an alternative to succinylcholine for RSI but recovery times are nearly doubled compared with a standard intubating dose of rocuronium. Magnesium sulfate significantly shortens the onset time of a standard intubating dose of rocuronium. We set out to investigate whether intravenous (IV) pretreatment with MgSO4 followed by a standard intubating dose of rocuronium achieved superior intubation conditions compared with succinylcholine. METHODS: Adults were randomized to receive a 15-minute IV infusion of MgSO4 (60 mg·kg-1) immediately before RSI with propofol 2 mg·kg-1, sufentanil 0.2 µg·kg-1 and rocuronium 0.6 mg·kg-1, or a matching 15-minute IV infusion of saline immediately before an identical RSI, but with succinylcholine 1 mg·kg-1. Primary end point was the rate of excellent intubating conditions 60 seconds after administration of the neuromuscular blocking agent and compared between groups using multivariable log-binomial regression model. Secondary end points were blood pressure and heart rate before induction, before and after intubation, and adverse events up to 24 hours postoperatively. RESULTS: Among 280 randomized patients, intubating conditions could be analyzed in 259 (133 MgSO4-rocuronium and 126 saline-succinylcholine). The rate of excellent intubating conditions was 46% with MgSO4-rocuronium and 45% with saline-succinylcholine. The analysis adjusted for gender and center showed no superiority of MgSO4-rocuronium compared with saline-succinylcholine (relative risk [RR] 1.06, 95% confidence interval [CI], 0.81-1.39, P = .659). The rate of excellent intubating conditions was higher in women (54% [70 of 130]) compared with men (37% [48 of 129]; adjusted RR 1.42, 95% CI, 1.07-1.91, P = .017). No significant difference between groups was observed for systolic and diastolic blood pressures. Mean heart rate was significantly higher in the MgSO4-rocuronium group. The percentage of patients with at least 1 adverse event was lower with MgSO4-rocuronium (11%) compared with saline-succinylcholine (28%) (RR 0.38, 95% CI, 0.22-0.66, P < .001). With saline-succinylcholine, adverse events consisted mainly of postoperative muscle pain (n = 26 [19%]) and signs of histamine release (n = 13 [9%]). With MgSO4-rocuronium, few patients had pain on injection, nausea and vomiting, or skin rash during the MgSO4-infusion (n = 5 [4%]). CONCLUSIONS: IV pretreatment with MgSO4 followed by a standard intubating dose of rocuronium did not provide superior intubation conditions to succinylcholine but had fewer adverse effects.

Discordant Clostridioides difficile diagnostic assay and treatment practice: a cross-sectional study in a tertiary care hospital, Geneva, Switzerland.

OBJECTIVES: To determine the proportion of patients who received a treatment for Clostridioides difficile infection (CDI) among those presenting a discordant C. difficile diagnostic assay and to identify patient characteristics associated with the decision to treat CDI. DESIGN: Cross-sectional study. SETTING: Monocentric study in a tertiary care hospital, Geneva, Switzerland. PARTICIPANTS: Among 4562 adult patients tested for C. difficile between March 2017 and March 2019, 208 patients with discordant tests' results (positive nucleic acid amplification test (NAAT+)/negative enzyme immunoassay (EIA-)) were included. MAIN OUTCOME MEASURES: Treatment for CDI. RESULTS: CDI treatment was administered in 147 (71%) cases. In multivariate analysis, an abdominal CT scan with signs of colitis (OR 14.7; 95% CI 1.96 to 110.8) was the only factor associated with CDI treatment. CONCLUSIONS: The proportion of NAAT+/EIA- patients who received treatment questions the contribution of the EIA for the detection of toxin A/B after NAAT to limit overtreatment. Additional studies are needed to investigate if other factors are associated with the decision to treat.

Walking Speed and Maximal Knee Flexion During Gait After Total Knee Arthroplasty: Minimal Clinically Important Improvement Is Not Determinable; Patient Acceptable Symptom State Is Potentially Useful.

BACKGROUND: Total knee arthroplasty (TKA) is the operation of choice in patients with end-stage knee osteoarthritis (OA). Up to 1 in 5 patients still encounter functional limitations after TKA, partly explaining patient dissatisfaction. Which gait ability to target after TKA remains unclear. To determine whether Minimal Clinical Important Improvement (MCII) or Patient Acceptable Symptom State (PASS) values could be derived from gait parameters recorded in patients with TKA. And, if so, to define those values. METHODS: In this ancillary study, we retrospectively analyzed gait parameters of patients scheduled for a unilateral TKA between 2011 and 2013. We investigated MCII and PASS values for walking speed and maximal knee flexion using anchor-based methods: 5 anchoring questions based on perceived body function and patients' satisfaction. RESULTS: Over the study period, 79 patients performed a clinical gait analysis the week before and 1 year after surgery, and were included in the present study. All clinical and gait parameters improved 1 year after TKA. Nevertheless, changes in gait outcomes were not associated with perceived body function or patients' satisfaction, precluding any MCII estimation in gait parameters. PASS values, however, could be determined as 1.2 m/s for walking speed and 50° for maximal knee flexion. CONCLUSION: In this study, we found that MCII and PASS values are not necessarily determinable for gait parameters after TKA in patients with end-stage OA. Using anchor questions based on perceived body function and patient's satisfaction, MCII could not be defined while PASS values were potentially useful. LEVEL OF EVIDENCE: Level III.