Electrocardiogram-based mortality prediction in patients with COVID-19 using machine learning.

BACKGROUND AND PURPOSE: The electrocardiogram (ECG) is frequently obtained in the work-up of COVID-19 patients. So far, no study has evaluated whether ECG-based machine learning models have added value to predict in-hospital mortality specifically in COVID-19 patients. METHODS: Using data from the CAPACITY-COVID registry, we studied 882 patients admitted with COVID-19 across seven hospitals in the Netherlands. Raw format 12-lead ECGs recorded within 72 h of admission were studied. With data from five hospitals (n = 634), three models were developed: (a) a logistic regression baseline model using age and sex, (b) a least absolute shrinkage and selection operator (LASSO) model using age, sex and human annotated ECG features, and (c) a pre-trained deep neural network (DNN) using age, sex and the raw ECG waveforms. Data from two hospitals (n = 248) was used for external validation. RESULTS: Performances for models a, b and c were comparable with an area under the receiver operating curve of 0.73 (95% confidence interval [CI] 0.65-0.79), 0.76 (95% CI 0.68-0.82) and 0.77 (95% CI 0.70-0.83) respectively. Predictors of mortality in the LASSO model were age, low QRS voltage, ST depression, premature atrial complexes, sex, increased ventricular rate, and right bundle branch block. CONCLUSION: This study shows that the ECG-based prediction models could be helpful for the initial risk stratification of patients diagnosed with COVID-19, and that several ECG abnormalities are associated with in-hospital all-cause mortality of COVID-19 patients. Moreover, this proof-of-principle study shows that the use of pre-trained DNNs for ECG analysis does not underperform compared with time-consuming manual annotation of ECG features.

Clinical characteristics of patients with suspected cardiac chest pain and angiographically normal coronary arteries in a secondary care hospital.

BACKGROUND: An important number of patients with suspected cardiac chest pain have non-obstructive coronary artery disease. Our purpose was to describe the clinical characteristics of patients with normal or near-normal coronary arteries in routine cardiological practice in a secondary care hospital. METHODS: In 2013, consecutive patients referred for invasive coronary angiography with suspected cardiac chest pain were analysed at a single-centre (Westfriesgasthuis, Hoorn, the Netherlands). Coronary arteries were defined as normal or near-normal if they showed no stenosis or only slight wall irregularities on visual assessment. Patients with a final non-cardiac diagnosis for the chest pain were excluded. RESULTS: A total of 558 patients were included. Of these, 151 (27%) showed normal or near-normal coronary arteries on visual assessment. This group of patients were significantly more often female (p < 0.001), younger (p < 0.001) and non-diabetic (p = 0.002). Forty percent of hospitalised patients who had normal or near-normal coronary arteries at coronary angiography showed an elevated troponin. CONCLUSION: In routine cardiological practice, around 1 out of 4 patients with suspected cardiac chest pain undergoing invasive angiography had normal or near-normal coronary arteries. We suggest that premenopausal women with suspected cardiac chest pain could be considered for non-invasive coronary imaging as a first step in clinical practice.

[EurSafety Health-Net: MRSA Eradication in Nursing Homes and Home Care - A Practice Report]. / EurSafety Health-Net: MRSA-Sanierung in der Pflege (MSP) - ein Praxisbericht.

In 2009 the project EurSafety Health-Net, funded by Interreg IVa, was initiated in order to create a cross-border quality alliance to enhance patient safety in the field of infectious diseases. Within this framework, several studies and projects addressing key topics of infection control were carried out. We describe the two-year project "MRSA decolonisation in care settings (MSP)", which aimed at evaluating a simple and economic way of decolonisation of non-hospitalised MRSA carriers in 2 districts in Lower Saxony. In the course of the project 181 decolonisations of MRSA carriers were performed by nursing homes and nursing services for outpatients in cooperation with the local public health authorities of the districts Ammerland and Grafschaft Bentheim. Of 181 cases 134 were eligible for statistical analysis. The project provided protocols for 2 different starting situations: 1) Continuing and completing a decolonisation treatment subsequent to a hospital stay by nursing services for outpatients or in a nursing home. 2) Starting a decolonisation treatment in a nursing home or by nursing services for outpatients. The carriers were provided with the required materials either by the hospitals (situation 1) or by the local public health authorities (situation 2) free of charge. The decolonisation treatment and the testing were offered only to carriers free of properties deemed as decolonisation obstacles and was applied without involvement of the general practitioner. Short- and long-term success of the 5 day decolonisation treatment was tested afterwards by two swabs (14 days and 6 months after the end of the treatment). The results of the 6-month control swabs showed that 45% of the carriers were successfully decolonised in the long term. All parties involved regarded the procedure of the MSP project as effective with respect to the target. Thus, even after the project was finished, both districts continued applying the MSP protocol.

Takotsubo cardiomyopathy shortly following pacemaker implantation-case report and review of the literature.

We describe a patient with acute heart failure shortly after pacemaker implantation. With the documentation of typical dyskinesia of the apical segments with hyperdynamic contractility of the basal segments and a normal coronary angiogram, pacemaker implantation-induced Takotsubo cardiomyopathy was diagnosed. Supportive care was administered and within several days the patient's symptoms resolved. After several weeks, the left ventricular function had fully recovered. A review of the literature on Takotsubo cardiomyopathy after pacemaker implantation is presented.

Seal gammaherpesviruses: identification, characterisation and epidemiology.

Phocid herpesvirus type 2 (PhHV-2), tentatively classified as a gammaherpesvirus, has been isolated from European and American harbour seals (Phoca vitulina). Here we describe the isolation and the molecular as well as biological characterisation of different PhHV-2 isolates from harbour seals and grey seals (Halichoerus grypus). Of 522 harbour seals and 231 grey seals that had been admitted to the seal research and rehabilitation centre in Pieterburen, The Netherlands, between 1992 and 2000, 38 and 18%, respectively, proved to have PhHV-2 neutralising antibodies. PhHV-2 was isolated from peripheral blood mononuclear cells (PBMCs) of 12 and 28% of these seropositive animals, respectively, and 26 and 56% of these cell samples, respectively, were positive by PCR analysis. Analysis of amino acid sequences of PCR products and of the growth characteristics of different PhHV-2 isolates indicated that harbour and grey seals are infected with distinct gamma-herpesviruses, which however, may co-circulate between the two species.

[Femoral shaft fracture and secondary diagnosis of ipsilateral femoral neck fracture. Typical constellation or a complication of the distal femoral nail (DFN)?]. / Femurschaftfraktur und sekundär diagnostizierte ipsilaterale Schenkelhalsfraktur. Typische Konstellation oder eine Komplikation des distalen Femurnagels (DFN)?

We present a case of two patients with a distal femur shaft fracture due to a high velocity trauma. Both were treated with a distal femur nail (DFN). After mobilisation a fracture of the neck of the femur was diagnosed which was not seen in the x-rays on admission. In this paper we discuss whether this is a typical constellation of ipsilateral fractures of the neck of the femur in femur shaft fractures or a complication of implantation of a DFN. Immediately after operative treatment of a femur shaft fracture specifically after high velocity trauma or in polytraumatized patients an x-ray of the hip in two plains should be made in the same narcosis. A possible fracture of the neck of the femur could be treated at same time. Post-operatively a further diagnostic should be done in case of suspicion, e.g. pain during mobilisation.

Hepatitis B surface antigen (HBsAg) derived from yeast cells (Hansenula polymorpha) used to establish an influence of antigenic subtype (adw2, adr, ayw3) in measuring the immune response after vaccination.

As a product of western world biotechnology the yeast (Saccharomyces cerevisiae) hepatitis B vaccine was introduced as antigenic subtype adw2. However, an HBsAg/adw2-vaccine may provide a good but not "optimal" immunologic response for infection with heterologous virus strains. The availability of the yeast Hansenula polymorpha HBsAg in three different antigenic forms (adw2, ayw3 and adr) enabled us to investigate the influence of variant amino acids in the binding of immune anti-HBs after vaccination. Hansenula-derived HBsAg was standardised on the basis of protein content at >95% purity. Standardisation was controlled by monoclonal anti-HBs binding in a well-conserved region. Sera were obtained after immunisation with type adw, ayw and adr vaccines. Direct binding of immune antibodies to homologous antigen (in EIA) was higher than to heterologous antigen except for the adr-related antibodies. Since the binding of the WHO reference anti-HBs was strongly reduced for the ayw and adr compared to the adw antigen, a similar binding profile for the three antigens on protein basis could result in 2-3-fold different anti-HBs level expressed in IU/l. Inhibition of Hansenula-derived HBsAg binding to solid phase monoclonal anti-HBs in enzyme immunoassays after incubation with serum anti-HBs confirmed the differential binding of serum anti-HBs with variant Hansenula-derived HBsAg. This variant (antigenic subtype) dependent reactivity of anti-HBs in immunoassays in combination with a variant specific WHO standard may limit the application of the threshold levels of 10 and 100 IU/l for seroconversion and seroprotection.

Comparison of video trainer and virtual reality training systems on acquisition of laparoscopic skills.

Training on a video trainer or computer-based minimally invasive surgery trainer leads to improved benchtop laparoscopic skill. Recently, improved operative performance from practice on a video trainer was reported. The purpose of this study was three fold: (a) to compare psychomotor skill improvement after training on a virtual reality (VR) system with that after training on a video-trainer, (VT) (b) to evaluate whether skills learned on the one training system are transferable to the other, and (c) to evaluate whether VR or VT training improves operative performance. For the study, 50 junior surgery residents completed baseline skill testing on both the VR and VT systems. These subjects then were randomized to either a VR or VT structured training group. After practice, the subjects were tested again on their VR and VT skills. To assess the effect of practice on operative performance, all second-year residents (n = 19) were evaluated on their operative performance during a laparoscopic cholecystectomy before and after skill training. Data are expressed as percentage of improvement in mean score/time. Analysis was performed by Student's paired t-test. The VR training group showed improvement of 54% on the VR posttest, as compared with 55% improvement by the VT group. The VR training group improved more on the VT posttest tasks (36%) than the VT training group improved on the VR posttest tasks (17%) (p <0.05). Operative performance improved only in the VR training group (p <0.05). Psychomotor skills improve after training on both VR and VT, and skills may be transferable. Furthermore, training on a minimally invasive surgery trainer, virtual reality system may improve operative performance during laparoscopic cholecystectomy.

Characterization of a human monoclonal antibody obtained after immunization with plasma vaccine and a booster with recombinant-DNA hepatitis B vaccine.

A human monoclonal antibody type IgG4, designated 1Ff4, was obtained by Epstein Barr virus transformation of peripheral blood lymphocytes from a hepatitis B vaccinee (HB-VAX: plasma-derived vaccine) after one boost of yeast recombinant DNA derived vaccine (Engerix-B). 1Ff4 binds preferentially to HBsAg/adw(2) and HBsAg/ayw(1). In binding experiments, it competes with antibodies induced by vaccination with HB-VAX-DNA (yeast recombinant) and HB-VAX (plasma-derived vaccine). 1Ff4 competes in part with a monoclonal antibody for the w/r region. Partial inhibition of binding of HBsAg/adw(2) to solid phase anti-HBs was detected, resembling inhibition obtained using other human monoclonal specific for the "a"-loop. 1Ff4 does not bind to linear peptides covering the two "a"-loops or to an adw(2)/G145R mutant, its binding to wild type HBsAg strongly depends on the presence of disulphide bonds. In a large series of HBsAg-positive samples from an endemic area, 1Ff4 antibodies were successfully used to discriminate between an adw(2) and an adrq+ strain. The characterisation of 1Ff4 and other human monoclonal anti-HBs antibodies may help to understand the fine specificity of protective antibodies elicited by immunization.

Administration of a human monoclonal antibody (TUVIRUMAB) to chronic hepatitis B patients pre-treated with lamivudine: monitoring of serum TUVIRUMAB in immune complexes.

A human monoclonal anti-hepatitis B antibody preparation (TUVIRUMAB) was administered 6 times over a 2-week period in a dose-escalating scheme to chronic hepatitis B patients pre-treated with lamivudine. The capacity of the TUVIRUMAB antibody to "neutralize" hepatitis B surface antigen in the circulation was investigated by means of experimental enzyme-immunoassays. Monoclonal antibody conjugates enabled the detection of HBsAg, TUVIRUMAB, and HBsAg/TUVIRUMAB complexes. The results showed that (1) TUVIRUMAB was able partially to "neutralize" in vitro and in vivo, (2) HBsAg/TUVIRUMAB complexes can be traced by assays that capture the complex at either its HBsAg or its TUVIRUMAB component, (3) the final concentration of TUVIRUMAB at the end of therapy varied greatly but seemed to be related to HBsAg production at the start of therapy, (4) for at least 14 days after discontinuation of therapy, a minimal HBsAg level could be maintained in the presence of a declining TUVIRUMAB titer in patients with less than 3 microg/ml HBsAg before the start of therapy, (5) three months after therapy, all HBsAg levels had returned to pre-treatment levels and TUVIRUMAB had disappeared.

Anti-HBs after hepatitis B immunization with plasma-derived and recombinant DNA-derived vaccines: binding to mutant HBsAg.

The G145R mutant of the small S-protein is a major escape mutant of hepatitis B virus observed in natural infection, after immunization and HBIG therapy. In a previous study we found that plasma-derived and recombinant DNA-derived vaccine HBsAg reacted differently with monoclonal antibodies sensitive for the G145R change. In the present study we investigated the binding of polyclonal anti-HBs obtained after immunization with plasma vaccine and recombinant DNA vaccine to synthetic peptides (adw(2), adr) and rHBsAg (HepG2) (ayw(3); wild type and a 145R mutant). Anti-HBs binding to synthetic peptids (25-mers, 7aa overlap) from the "a"-loop was significantly reduced by the G145R substitution and by changing the amino acid sequence from adw(2) into adr. With mutant G145R rHBsAg the inhibitory activity of vaccine anti-HBs was decreased compared to rHBsAg wild type. In general only minor differences were observed between plasma vaccine and recombinant DNA vaccine related antibody responses. However, the individual heterogeneity in epitope specific reactivity with its possible consequences for protection (against escape mutants) is not reflected in an anti-HBs titer by standard anti-HBs assays. The presented differentiation in anti-HBs response after immunization may deliver new tools for evaluation of future vaccines.

Improving operative performance using a laparoscopic hernia simulator.

BACKGROUND: Traditionally, the acquisition of surgical skill has occurred entirely in the operating room. To meet the expanding challenges of cost containment and patient safety, novel methods of surgical training utilizing ex-vivo workstations are being developed. The purpose of our study was to evaluate the impact of a laparoscopic training curriculum on surgical residents' operative performance. METHODS: Twenty-one surgery residents completed baseline laparoscopic total extraperitoneal (TEP) hernia repairs. Operative performance was evaluated using a validated global assessment tool. Each resident was then randomized to a control group or a trained group. A CD ROM, video, and simulator were used for training. At the end of the study, each resident's operative performance was again evaluated. RESULTS: Improvement was significantly greater in the trained group in five of the eight individual global assessment areas as well as the composite score (P <0.05). Questionnaire data suggested that training resulted in improved understanding of the TEP hernia repair (P = 0.01) and an increased willingness to offer the operation to patients with nonrecurrent unilateral hernias (P = 0.02). CONCLUSIONS: A multimodality laparoscopic TEP hernia curriculum improves residents' knowledge of the TEP hernia repair and comfort in performing the procedure, and may also improve actual operative performance.

Prognostic significance of nonfatal myocardial reinfarction in survivors of a first infarction.

BACKGROUND: Patients who develop a reinfarction are at increased risk for subsequent reinfarctions and death. However, follow-up studies in these patients are rare. OBJECTIVE: The purpose of this study was to examine the risk of mortality after a first myocardial reinfarction and to determine the independent contribution of nonfatal reinfarction to the risk of subsequent mortality. METHODS: The prognostic value of nonfatal reinfarction was assessed in a large series (n=3097) of patients with a first myocardial infarction who participated in the ASPECT trial, comparing coumarin or matching placebo. RESULTS: A second myocardial infarction was documented in 299 patients (82% Q-wave infarctions), 45 (15%) of which were fatal. Of the 254 nonfatal reinfarctions, 31 patients (12%) died during subsequent follow-up. After adjustment for baseline characteristics, the relative risks of nonfatal reinfarction for subsequent cardiac mortality at one month were: 2.90 (1.49-5.64), at one year: 2.50 (1.47-4.23) and at three years: 2.71 (1.77-4.17). Rates of death or a second reinfarction in patients who did not undergo a revascularisation procedure after a first reinfarction were almost three times higher than in patients who did have PTCA or bypass surgery after a reinfarction (38% versus 14%; p<0.0001). CONCLUSION: This study population with three-year follow-up confirms that nonfatal reinfarction carries a strong and independent risk for recurrent reinfarction and subsequent mortality. Thus, prevention of reinfarction by intensive treatment might contribute in reduction of mortality.

Evaluating surgical competency with the American Board of Surgery In-Training Examination, skill testing, and intraoperative assessment.

BACKGROUND: Evaluation of surgical competency should include assessment of knowledge, technical skill, and judgment. The purpose of this study was to determine the relationship between the American Board of Surgery In-Training Examination (ABSITE), skill testing, and intraoperative assessment. METHODS: Postgraduate year 2 (PGY-2) and postgraduate year 3 (PGY-3) surgery residents (n = 33) were tested by means of (1) the ABSITE, (2) skill testing on a laparoscopic video-trainer, and (3) intra-operative global assessments during laparoscopic cholecystectomy. The Pearson correlation was used to determine the correlation between the ABSITE, skill testing, and intraoperative assessments. For the comparison of PGY-2 and PGY-3 resident performance, Wilcoxon rank sum tests were used. RESULTS: The ABSITE scores did not correlate with skill testing or intraoperative assessments (not significant). Skill testing correlated with the intraoperative composite score and with 4 of 8 operative performance criteria (P<.05). The ABSITE scores and skill testing were not different for PGY-2 and PGY-3 residents (not significant). Intraoperative assessments were better in 5 of 8 criteria and the composite score for PGY-3 versus PGY-2 residents (P<.05), which demonstrated construct validity. CONCLUSIONS: The ABSITE measures knowledge but does not correlate with technical skill or operative performance. Residency programs should use multiple assessment instruments to evaluate competency. There may be a role for both skill testing and intraoperative assessment in the evaluation of surgical competency.

Laparoscopic training on bench models: better and more cost effective than operating room experience?

BACKGROUND: Developing technical skill is essential to surgical training, but using the operating room for basic skill acquisition may be inefficient and expensive, especially for laparoscopic operations. This study determines if laparoscopic skills training using simulated tasks on a video-trainer improves the operative performance of surgery residents. STUDY DESIGN: Second- and third-year residents (n= 27) were prospectively randomized to receive formal laparoscopic skills training or to a control group. At baseline, residents had a validated global assessment of their ability to perform a laparoscopic cholecystectomy based on direct observation by three evaluators who were blinded to the residents' randomization status. Residents were also tested on five standardized video-trainer tasks. The training group practiced the video-trainer tasks as a group for 30 minutes daily for 10 days. The control group received no formal training. All residents repeated the video-trainer test and underwent a second global assessment by the same three blinded evaluators at the end of the 1-month rotation. Within-person improvement was determined; improvement was adjusted for differences in baseline performance. RESULTS: Five residents were unable to participate because of scheduling problems; 9 residents in the training group and 13 residents in the control group completed the study. Baseline laparoscopic experience, video-trainer scores, and global assessments were not significantly different between the two groups. The training group on average practiced the video-trainer tasks 138 times (range 94 to 171 times); the control group did not practice any task. The trained group achieved significantly greater adjusted improvement in video-trainer scores (five of five tasks) and global assessments (four of eight criteria) over the course of the four-week curriculum, compared with controls. CONCLUSIONS: Intense training improves video-eye-hand skills and translates into improved operative performance for junior surgery residents. Surgical curricula should contain laparoscopic skills training.

Measuring operative performance after laparoscopic skills training: edited videotape versus direct observation.

BACKGROUND AND PURPOSE: Global assessment by direct observation has been validated for evaluating operative performance of surgery residents after formal skills training but is time-consuming. The purpose of this study was to compare global assessment performed from edited videotape with scores from direct observation. MATERIALS AND METHODS: Junior surgery residents (N = 22) were randomized to 2 weeks of formal videotrainer skills training or a control group. Laparoscopic cholecystectomy was performed at the beginning and end of the rotation, and global assessment scores were compared for the training and control groups. Laparoscopic videotapes were edited: initial (2 minutes), cystic duct/artery (6 minutes), and fossa dissection (2 minutes). Two independent raters performed both direct observation and videotape assessments, and scores were compared for each rater and for interrater reliability using a Spearman correlation. RESULTS: Correlation coefficients for videotape versus direct observation for five global assessment criteria were <0.33 for both raters (NS for all values). The correlation coefficient for interrater reliability for the overall score was 0.57 (P = 0.01) for direct observation v 0.28 (NS) for videotape. The trained group had significantly better overall performance than the control group according to the assessment by direct observation (P = 0.02) but not by videotape assessment (NS). CONCLUSIONS: Direct observation demonstrated improved overall performance of junior residents after formal skills training on a videotrainer. Global assessment from an edited 10-minute videotape did not correlate with direct observation and had poor interrater reliability. Efficient and valid methods of evaluating operative performance await development.

Identification of high-risk residents.

BACKGROUND: Identification of high-risk residents allows remediation and support for administrative action when necessary. This study characterizes differences in documentation of marginally performing residents in a general surgery residency. METHODS: High-risk residents were identified by the former program director. Twenty-four of one hundred fifteen residents over a 10-year period had one to four problematic areas: cognitive, synthetic, family/health, and interpersonal skills. Outcomes included finished (18), voluntary withdrawal (1), and involuntary withdrawal (5). A case-control study matching controls to cases by date of entry into the training program was used. Records were reviewed for demographics, preentry qualifications, American Board of Surgery In-Training Exam (ABSITE) scores, letters of complaint or praise, events of counseling, and monthly ratings. The records of 48 residents were reviewed. Ward evaluations were on eight categories with a 5-point Leikert scale (3-unacceptable to 7-outstanding). The evaluation score assigns points only to low ratings. High scores represent progressively poorer performance. A Wilcoxon signed ranks test was used to compare the cases and controls for continuous variables. The McNemar test was used in comparisons of categorical data with binary outcomes. Exact P values are reported. RESULTS: Objective data were similar for both groups. Study residents tended to score higher on monthly evaluations at Year 2 and by Year 3 this achieved significance (0.026). Study residents were more likely to have negative faculty letters (0.016) and events of counseling by a faculty member (0.017) and the program director (0.005). CONCLUSIONS: Identification of residents at risk should begin as early as possible during training. A combination of faculty evaluations and evidence of letters of counseling can detect high-risk residents. Programs may use such indicators to support decisions regarding remedial work or administrative action.