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Aims: We aim to evaluate the clinical pharmacokinetics of a single dose interleukin-6 (IL-6) antibody tocilizumab (TCZ) in methylprednisolone (MP)-treated COVID-19 patients with cytokine storm syndrome (CSS). Methods: MP pre-treated patients with COVID-19-associated CSS, defined as at least two elevations of C-reactive protein (CRP) >100 mg/L, ferritin >900 mu g/L or D-dimers >1500 mu g/L, received intravenous TCZ (8 mg/kg, max. 800 mg) upon clinical deterioration. A nonlinear-mixed effects model was developed based on TCZ serum concentrations and dosing information. Population pharmacokinetic parameters were estimated and concentration-time profiles were plotted against individual predicted values. Fixed dose simulations were subsequently performed based on the final model. Results:In total 40 patients (mean [SD] age: 62 [12] years, 20% female, body weight: 87 [17] kg) with COVID-19 induced CSS were evaluated on pharmacokinetics and laboratory parameters. A biphasic elimination of TCZ serum concentration was described by a homogeneous population pharmacokinetic model. Serum TCZ concentrations above the 1 mu g/L target saturation threshold were covered for 16 days in all evaluated patients treated with a single dose of 8 mg/kg. In a simulation with TCZ 400 mg fixed dose, this condition of full IL-6 receptor occupancy at minimum serum concentration was also met. Conclusions: A single dose (8 mg/kg, max. 800 mg) is sufficient to cover a period of 16 days of IL-6-mediated hyperinflammation in COVID-19-induced CSS in MP-treated patients. Based on body weight PK simulations, a fixed-dose tocilizumab of 400 mg should be considered to prevent overtreatment, future drug shortage and unnecessary drug expenditure.

Background Sepsis is often accompanied with acute kidney injury (AKI). The incidence of AKI in patients visiting the emergency department (ED) with sepsis according to the new SOFA criteria is not exactly known, because the definition of sepsis has changed and many definitions of AKI exist. Given the important consequences of early recognition of AKI in sepsis, our aim was to assess the epidemiology of sepsis-associated AKI using different AKI definitions (RIFLE, AKIN, AKIB, delta check, and KDIGO) for the different sepsis classifications (SIRS, qSOFA, and SOFA). Methods We retrospectively enrolled patients with sepsis in the ED in three hospitals and applied different AKI definitions to determine the incidence of sepsis-associated AKI. In addition, the association between the different AKI definitions and persistent kidney injury, hospital length of stay, and 30-day mortality were evaluated. Results In total, 2065 patients were included. The incidence of AKI was 17.7–51.1%, depending on sepsis and AKI definition. The highest incidence of AKI was found in qSOFA patients when the AKIN and KDIGO definitions were applied (51.1%). Applying the AKIN and KDIGO definitions in patients with sepsis according to the SOFA criteria, AKI was present in 37.3% of patients, and using the SIRS criteria, AKI was present in 25.4% of patients. Crude 30-day mortality, prolonged length of stay, and persistent kidney injury were comparable for patients diagnosed with AKI, regardless of the definition used. Conclusion The incidence of AKI in patients with sepsis is highly dependent on how patients with sepsis are categorised and how AKI is defined. When AKI (any definition) was already present at the ED, 30-day mortality was high (22.2%). The diagnosis of AKI in sepsis can be considered as a sign of severe disease and helps to identify patients at high risk of adverse outcome at an early stage.

We report a 74-year-old patient who developed an acute aortic syndrome (AAS) with intramural haematoma (IMH) during treatment with nintedanib, a tyrosine kinase inhibitor. As we suspected a role for nintedanib, this was immediately interrupted. Four months later, a computed tomographic angiography (CTA) showed significant regression of the IMH. Therefore, we state that, when patients use nintedanib and develop acute chest or back pain, diagnostic work-up for AAS should be considered. Furthermore, other risk factors for AAS, such as hypertension, genetic diseases and comedication should be taken into account when prescription of medication of this class is considered.

ObjectiveTo mitigate the burden of COVID-19 on the healthcare system, information on the prognosis of the disease is needed. The recently developed RISE UP score has very good discriminatory value with respect to short-term mortality in older patients in the emergency department (ED). It consists of six items: age, abnormal vital signs, albumin, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and bilirubin. We hypothesized that the RISE UP score could have discriminatory value with regard to 30-day mortality in ED patients with COVID-19.SettingTwo EDs of the Zuyderland Medical Centre (MC), secondary care hospital in the Netherlands.ParticipantsThe study sample consisted of 642 adult ED patients diagnosed with COVID-19 between March 3rd until May 25th 2020. Inclusion criteria were: 1) admission to the hospital with symptoms suggestive of COVID-19, and 2) positive result of the polymerase chain reaction (PCR), or (very) high suspicion of COVID-19 according to the chest computed tomography (CT) scan.OutcomePrimary outcome was 30-day mortality, secondary outcome was a composite of 30-day mortality and admission to intensive care unit (ICU).ResultsWithin 30 days after presentation, 167 patients (26.0%) died and 102 patients (15.9%) were admitted to ICU. The RISE UP score showed good discriminatory value with respect to 30-day mortality (AUC 0.77, 95% CI 0.73-0.81), and to the composite outcome (AUC 0.72, 95% CI 0.68-0.76). Patients with RISE UP scores below 10% (121 patients) had favourable outcome (0% mortality and 5% ICU admissions). Patients with a RISE UP score above 30% (221 patients) were at high risk of adverse outcome (46.6% mortality and 19% ICU admissions).ConclusionThe RISE UP score is an accurate prognostic model for adverse outcome in ED patients with COVID-19. It can be used to identify patients at risk of short-term adverse outcome, and may help guiding decision-making and allocating healthcare resources.

Objective Older emergency department (ED) patients are at high risk of mortality, and it is important to predict which patients are at highest risk. Biomarkers such as lactate, high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), D-dimer and procalcitonin may be able to identify those at risk. We aimed to assess the discriminatory value of these biomarkers for 30-day mortality and other adverse outcomes. Design Prospective cohort study. On arrival of patients, five biomarkers were measured. Area under the curves (AUCs) and interval likelihood ratios (LRs) were calculated to investigate the discriminatory value of the biomarkers. Setting ED in the Netherlands. Participants Older (≥65 years) medical ED patients, referred for internal medicine or gastroenterology. Primary and secondary outcome measures 30-day mortality was the primary outcome measure, while other adverse outcomes (intensive care unit/medium care unit admission, prolonged length of hospital stay, loss of independent living and unplanned readmission) were the composite secondary outcome measure. Results The median age of the 450 included patients was 79 years (IQR 73–85). In total, 51 (11.3%) patients died within 30 days. The AUCs of all biomarkers for prediction of mortality were sufficient to good, with the highest AUC of 0.73 for hs-cTnT and NT-proBNP. Only for the highest lactate values, the LR was high enough (29.0) to be applicable for clinical decision making, but this applied to a minority of patients. The AUC for the composite secondary outcome (intensive and medium care admission, length of hospital stay >7 days, loss of independent living and unplanned readmission within 30 days) was lower, ranging between 0.58 and 0.67. Conclusions Although all five biomarkers predict 30-day mortality in older medical ED patients, their individual discriminatory value was not high enough to contribute to clinical decision making. Trial registration number NCT02946398; Results.

Hospitalization for corona virus disease 2019 (COVID-19) may be followed by complications after discharge. We aimed to evaluate mortality, readmission rate, and readmission characteristics after hospitalization with COVID-19.A retrospective cohort study METHODS: Inclusion of all patients hospitalized for COVID-19 between March 1, 2020, and June 1, 2020 in Zuyderland Medical Centre, The Netherlands. Main outcome measures were mortality and readmission after hospitalization. Univariate and multivariate regression analysis were performed to identify risk factors for death and readmission.A total of 769 patients hospitalized with COVID-19 (mean age 70 ± 14 years; 39% female) were included in the study. In-hospital mortality was 22.4% , as such 596 patients were discharged alive and followed after discharge with a median of 80 days (IQR 66-91). Total mortality after discharge was 6.4% (n=38) and readmission rate was 11.7% (n=70). Main reasons for readmission were respiratory insufficiency (31%), arterial and venous thrombotic events (16%) or related to a chronic comorbidity (14%). Mortality rates were higher in older patients and patients who experienced delirium during hospital stay. Risk factors for readmission were male sex, discharge to a long-term care facility and COPD.1 out of 6 COVID-19 positive patients died or was readmitted after discharge. This shows an ongoing vulnerability of COVID-19 patients. Physicians and policy makers should consider this high rate when making decisions on discharge, hospital-capacity planning, and patient monitoring after discharge.

ObjectivesTo prospectively investigate in patients with severe COVID-19-associated cytokine storm syndrome (CSS) whether an intensive course of glucocorticoids with or without tocilizumab accelerates clinical improvement, reduces mortality and prevents invasive mechanical ventilation, in comparison with a historic control group of patients who received supportive care only.MethodsFrom 1 April 2020, patients with COVID-19-associated CSS, defined as rapid respiratory deterioration plus at least two out of three biomarkers with important elevations (C-reactive protein >100 mg/L; ferritin >900 µg/L; D-dimer >1500 µg/L), received high-dose intravenous methylprednisolone for 5 consecutive days (250 mg on day 1 followed by 80 mg on days 2–5). If the respiratory condition had not improved sufficiently (in 43%), the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, single infusion) was added on or after day 2. Control patients with COVID-19-associated CSS (same definition) were retrospectively sampled from the pool of patients (n=350) admitted between 7 March and 31 March, and matched one to one to treated patients on sex and age. The primary outcome was ≥2 stages of improvement on a 7-item WHO-endorsed scale for trials in patients with severe influenza pneumonia, or discharge from the hospital. Secondary outcomes were hospital mortality and mechanical ventilation.ResultsAt baseline all patients with COVID-19 in the treatment group (n=86) and control group (n=86) had symptoms of CSS and faced acute respiratory failure. Treated patients had 79% higher likelihood on reaching the primary outcome (HR: 1.8; 95% CI 1.2 to 2.7) (7 days earlier), 65% less mortality (HR: 0.35; 95% CI 0.19 to 0.65) and 71% less invasive mechanical ventilation (HR: 0.29; 95% CI 0.14 to 0.65). Treatment effects remained constant in confounding and sensitivity analyses.ConclusionsA strategy involving a course of high-dose methylprednisolone, followed by tocilizumab if needed, may accelerate respiratory recovery, lower hospital mortality and reduce the likelihood of invasive mechanical ventilation in COVID-19-associated CSS.

ObjectiveTo compare survival of subjects with COVID-19 treated in hospitals that either did or did not routinely treat patients with hydroxychloroquine or chloroquine.MethodsWe analysed data of COVID-19 patients treated in 9 hospitals in the Netherlands. Inclusion dates ranged from February 27th 2020, to May 15th, when the Dutch national guidelines no longer supported the use of (hydroxy)chloroquine. Seven hospitals routinely treated subjects with (hydroxy)chloroquine, two hospitals did not. Primary outcome was 21-day all-cause mortality. We performed a survival analysis using log-rank test and Cox-regression with adjustment for age, sex and covariates based on premorbid health, disease severity, and the use of steroids for adult respiratory distress syndrome, including dexamethasone.ResultsAmong 1893 included subjects, 21-day mortality was 23.4% in 1552 subjects treated in hospitals that routinely prescribed (hydroxy)chloroquine, and 17.0% in 341 subjects that were treated in hospitals that did not. In the adjusted Cox-regression models this difference disappeared, with an adjusted hazard ratio of 1.17 (95%CI 0.88-1.55). When stratified by actually received treatment in individual subjects, the use of (hydroxy)chloroquine was associated with an increased 21-day mortality (HR 1.58; 95%CI 1.25-2.01) in the full model.ConclusionsAfter adjustment for confounders, mortality was not significantly different in hospitals that routinely treated patients with (hydroxy)chloroquine, compared with hospitals that did not. We compared outcomes of hospital strategies rather than outcomes of individual patients to reduce the chance of indication bias. This study adds evidence against the use of (hydroxy)chloroquine in patients with COVID-19.

BackgroundOlder emergency department (ED) patients often have complex problems and severe illnesses with a high risk of adverse outcomes. It is likely that these older patients are troubled with concerns, which might reflect their preferences and needs concerning medical care. However, data regarding this topic are lacking.MethodsThis study is a sub study of a prospective, multicenter, observational cohort study among older medical ED patients (≥65 years). Patients or their caregivers were asked about their illness-related concerns during the first stage of the ED visit using a questionnaire. All concerns were categorized into 10 categories, and differences between patients and caregivers, and between age groups were analyzed. Odds Ratios were calculated to determine the association of the concerns for different adverse outcomes.ResultsMost of the 594 included patients (or their caregivers) were concerned (88%) about some aspects of their illness or their need for medical care. The most often reported concerns were about the severity of disease (43.6%), functional decline (9.4%) and dying (5.6%). Caregivers were more frequently concerned than patients (p7 days, loss of independent living and unplanned readmission within 30 days) (OR 2.32; 95%CI: 1.12-4.82). In addition, unspecified concerns were associated with mortality (OR 1.88; 95%CI: 1.09-3.22).ConclusionThe majority of older patients and especially their caregivers are concerned about their medical condition or need for medical care when they visit the ED. These concerns are associated with adverse outcomes and most likely reflect their needs regarding medical care. More attention should be paid to these concerns because they may offer opportunities to reduce anxiety and provide care that is adjusted to their needs.Trial registrationThis study was registered on clinicalTriagls.gov (NCT02946398).

Background/Objectives: Currently, accurate clinical models that predict short-term mortality in older (>= 65 years) emergency department (ED) patients are lacking. We aimed to develop and validate a prediction model for 30-day mortality in older ED patients that is easy to apply using variables that are readily available and reliably retrievable during the short phase of an ED stay.Methods: Prospective multi-centre cohort study in older medical ED patients. The model was derived through logistic regression analyses, externally validated and compared with other well-known prediction models (Identification of Seniors at Risk (ISAR), ISAR-Hospitalised Patients, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Modified Early Warning Score (MEWS)).Results: Within 30 days after presentation, 66 (10.9%) of 603 patients in the derivation cohort and 105 (13.3%) of 792 patients in the validation cohort died. The newly developed model included 6 predictors: age, >= 2 abnormal vital signs, serum albumin, blood urea nitrogen, lactate dehydrogenase, and bilirubin. The discriminatory value of the model for mortality was very good with an AUC of 0.84 in the derivation and 0.83 in the validation cohort. The final model was excellently calibrated (Hosmer-Lemeshow p-value 0.89). The discriminatory value of the model was significantly higher than that of the four risk stratification scores (highest AUC of 0.69 for ISAR score, p-value 0.007).Conclusion: We developed and externally validated an accurate and simplified prediction model for 30-day mortality in older ED patients. This model may be useful to identify patients at risk of short-term mortality and to apply personalised medical care.

Background: COVID-19 is associated with cytokine release syndrome (CRS), which contributes to morbidity and mortality Anecdotal reports suggest that CRS impro

Background Older patients (≥65 years old) experience high rates of adverse outcomes after an emergency department (ED) visit. Reliable tools to predict adverse outcomes in this population are lacking. This manuscript comprises a study protocol for the Risk Stratification in the Emergency Department in Acutely Ill Older Patients (RISE UP) study that aims to identify predictors of adverse outcome (including triage- and risk stratification scores) and intends to design a feasible prediction model for older patients that can be used in the ED. Methods The RISE UP study is a prospective observational multicentre cohort study in older (≥65 years of age) ED patients treated by internists or gastroenterologists in Zuyderland Medical Centre and Maastricht University Medical Centre+ in the Netherlands. After obtaining informed consent, patients characteristics, vital signs, functional status and routine laboratory tests will be retrieved. In addition, disease perception questionnaires will be filled out by patients or their caregivers and clinical impression questionnaires by nurses and physicians. Moreover, both arterial and venous blood samples will be taken in order to determine additional biomarkers. The discriminatory value of triage- and risk stratification scores, clinical impression scores and laboratory tests will be evaluated. Univariable logistic regression will be used to identify predictors of adverse outcomes. With these data we intend to develop a clinical prediction model for 30-day mortality using multivariable logistic regression. This model will be validated in an external cohort. Our primary endpoint is 30-day all-cause mortality. The secondary (composite) endpoint consist of 30-day mortality, length of hospital stay, admission to intensive- or medium care units, readmission and loss of independent living. Patients will be followed up for at least 30 days and, if possible, for one year. Discussion In this study, we will retrieve a broad range of data concerning adverse outcomes in older patients visiting the ED with medical problems. We intend to develop a clinical tool for identification of older patients at risk of adverse outcomes that is feasible for use in the ED, in order to improve clinical decision making and medical care. Trial registration Retrospectively registered on clinicaltrials.gov (NCT02946398; 9/20/2016). Electronic supplementary material The online version of this article (10.1186/s12877-019-1078-2) contains supplementary material, which is available to authorized users.

Background:The cytokine storm syndrome (CSS) associated with COVID-19 pneumonia occurs in up to 20% of the admitted patients causing high morbidity and mortality [1]. In the COVID High-intensity Immunosuppression in Cytokine storm syndrome (CHIC) study [1] we reported that CSS patients, who despite high-dose methylprednisolone (MP) treatment still showed severe respiratory deterioration, received subsequent single dose tocilizumab (TCZ) treatment. Our clinical experience with TCZ, every 4 weeks in RA, where a pre-dose serum concentration of > 1 µg/ml is sufficient to block all interleukin (IL)-6 receptors and thereby induce and maintain clinical remission, prompted further investigation of TCZ pharmacokinetics in patients with COVID-19 CSS [1,2].Objectives:In this pharmacokinetic study we investigated the clinical-pharmacokinetic rationale for a single TCZ dose in a subset of COVID19 induced CSS patients.Methods:Patients with COVID-19-associated CSS, defined as rapid respiratory deterioration plus at least two biomarker elevations (C-reactive protein (CRP) >100 mg/L; ferritin >900 μg/L; D-dimers >1500 μg/L), received per protocol high-dose intravenous MP for 5 consecutive days. If the respiratory condition had not improved sufficiently, TCZ (8 mg/kg, max. 800 mg) single infusion was added on or after day 2[1]. TCZ serum samples were drawn at TCZ day 1, 3 and 10 to assess TCZ serum concentrations with a validated ELISA-method. A nonlinear-mixed effects model was developed based on all concentration time data to characterise TCZ pharmacokinetics (NONMEM). Subsequently individual pharmacokinetic parameters (AUC0-inf, Cmax, time above 1 µg/ml) were estimated and TCZ concentration-time observations were plotted against the individual predicted concentrations to visualize the complete TCZ concentration-time curve.Results:In total, 34 patients with COVID19 induced CSS still showing clinical deterioration upon MP treatment received TCZ per protocol [mean (SD) age: 62 (12) years, 22% female, baseline mean (SD) bodyweight: 87 (17) kg, CRP: 108 (833) mmol/L, ferritin: 1653 (911) µg/L, D-dimers 4462 (7272) µg/L]. TCZ clearance was described by a homogeneous population-kinetics model yielding 87 serum samples. TCZ serum concentrations followed a biphasic course [Distribution volume 5.0 L (3.3-7.3), Area Under the Curve0-∞1st dose (682 (397-913) mg/L*days), Cmax 137 mg/L (88 – 199), half-life (linear) 3.5 days (2.3-4.1)]. In all patients, TCZ serum concentrations remained above the theoretical maximum IL-6 receptor occupancy concentration of 1 µg/ml for at least 12 days, depicted in Figure 1.Figure 1.Predicted concentration-time profiles after single dose tocilizumab in 34 methylpred-nisolone pretreated patients with COVID-19 induced cytokine storm syndrome. Dashed line: maximum IL-6 receptor occupancy concentration 1 µg/mlConclusion:Based on our study results on the pharmacokinetics of TCZ in patients with severe COVID-19 induced CSS we conclude that the clearance of TCZ is faster compared to RA-patients at steady state. However, our observations indicate that a single dose of tocilizumab in CSS-patients is enough to cover IL-6 mediated hyperinflammation. Restricting TCZ to a single dosage can prevent overtreatment, drug shortage and saves costs, while still maintaining efficacy, as most patients will have overcome their hyperinflammatory period of the CSS after 10-14 days.References:[1]Ramiro S. Mostard R.L.M. et al. Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study. Ann Rheum Dis 2020;79(9):1143-1151.[2]Nishimoto N, Terao K et al. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood. 2008;112:3959-3964.Acknowledgements:The authors are grateful to all patients, nurses and physicians who participated in this study.Disclosure of Interests:None declared

In 1%–5% of all acute Q fever infections, chronic Q fever develops, mostly manifesting as endocarditis, infected aneurysms, or infected vascular prostheses. In this study, we investigated the diagnostic value of 18F-FDG PET/CT in chronic Q fever at diagnosis and during follow-up. Methods: All adult Dutch patients suspected of chronic Q fever who were diagnosed since 2007 were retrospectively included until March 2015, when at least one 18F-FDG PET/CT scan was obtained. Clinical data and results from 18F-FDG PET/CT at diagnosis and during follow-up were collected. 18F-FDG PET/CT scans were prospectively reevaluated by 3 nuclear medicine physicians using a structured scoring system. Results: In total, 273 patients with possible, probable, or proven chronic Q fever were included. Of all 18F-FDG PET/CT scans performed at diagnosis, 13.5% led to a change in diagnosis. Q fever–related mortality rate in patients with and without vascular infection based on 18F-FDG PET/CT was 23.8% and 2.1%, respectively (P 5 0.001). When 18F-FDG PET/CT was added as a major criterion to the modified Duke criteria, 17 patients (1.9-fold increase) had definite endocarditis. At diagnosis, 19.6% of 18F-FDG PET/CT scans led to treatment modification. During follow-up, 57.3% of 18F-FDG PET/CT scans resulted in treatment modification. Conclusion: 18F-FDG PET/CT is a valuable technique in diagnosis of chronic Q fever and during follow-up, often leading to a change in diagnosis or treatment modification and providing important prognostic information on patient survival.

Objectives Initial antibiotic treatment of severe infections can lead to clinical deterioration due to sudden endotoxin release and concomitant exaggerated inflammatory response. Antibiotic-induced morphological changes may contribute to this phenomenon. High-dose ceftazidime, which inhibits penicillin-binding protein (PBP)-1 in Gram-negative bacteria, causes quick bacteriolysis and low endotoxin release. Low-dose ceftazidime leads to PBP-3 inhibition, which causes bacterial filament formation, associated with high endotoxin releases. PBP-2-specific antibiotics induce spheroplasts, again associated with low endotoxin release. We hypothesized that antibiotic type, concentration and regimen influence bacterial morphology, endotoxin levels and inflammatory response. Methods Neutropenic mice with Escherichia coli or Pseudomonas aeruginosa sepsis were treated with ceftazidime or meropenem 10-320 mg/kg as an intravenous bolus or as continuous tail vein infusions of 0.1 mL/h. Four hours later, bacterial counts, morphology, plasma endotoxin, pro-inflammatory cytokines [tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)] and antibiotic concentrations were measured. Results Continuous infusion of 80 mg/kg ceftazidime was the lowest dose preventing filaments in E. coli infections. Bolus treatment resulted in filament formation, irrespective of the dose. During continuous treatment, IL-6 and TNF-alpha concentrations were higher compared with bolus treatment and controls for both antibiotics and both strains. A clear relationship between cfu counts in muscle and circulating IL-6 was shown (r=- 0.579, P=0.007), suggesting that plasma IL-6 is a valuable indicator of bacterial killing at the infection site. Conclusions Our findings show that not PBP affinity but the method of antibiotic administration is crucial during initial treatment of severe infections.

Toxocara seroprevalence and the relation between Toxocara seroprevalence and allergic asthma were investigated in Dutch schoolchildren aged 4-6 years. Data on Toxocara antibodies, allergen-specific immunoglobulin E, allergic manifestations, and risk factors (pets and playgrounds) were obtained from 235 children from The Hague and 477 from Rotterdam, the Netherlands. The surveys were carried out from September 1987 to January 1988 in The Hague and in March and April 1989 in Rotterdam. Logistic regression was used to evaluate putative relations. Toxocara seroprevalence was higher in The Hague (11%) than in Rotterdam (6%), but this difference was not quite significant. Seroprevalences varied widely among schools. No differences between socioeconomic categories or between the sexes were found. Occurrences of asthma/recurrent bronchitis and hospitalization due to asthma/recurrent bronchitis were significantly associated with seroprevalence. Furthermore, a marginally significant relation with eczema was found. Immunoglobulin E specific for inhaled allergens occurred significantly more often in the Toxocara-seropositive group. The risk factors investigated were not related to seroprevalence. It is suggested that Toxocara, among other environmental factors, may stimulate polyclonally immunoglobulin E production, including allergen-specific immunoglobulin E, and thus may contribute to the manifestation of allergic asthma and possibly of eczema in children predisposed to allergy.

The degree of hydrops in guinea pig ears that had undergone unilateral endolymphatic sac and duct obliteration was quantified. For 15 guinea pigs from a prior study, the correlation between the degree of hydrops and several electrophysiologic measures of the functional state of the cochlea was determined. A significant correlation between the degree of hydrops and a reduction in the low-frequency cochlear microphonic evoked by a 29-Hz tone was found. No correlation was found between the degree of hydrops and the magnitude of the summating potential evoked by 8-kHz probes. A weak correlation was found between the degree of hydrops and a reduction in the compound action potential evoked by 2-kHz probes. Possible differences in the way the endolymphatic duct obliteration exerts its effect on the different cochlear potentials are discussed.

A 75 year old man was found unconscious in his bath. He had had a coronary bypass operation and pacemaker implanted because of syncope with bradyarrhythmia, and, more recently, prostate carcinoma with bone metastases had been diagnosed, for which he was being treated with antiandrogens. Examination revealed an unresponsive patient with a Glasgow coma score of 1-1-1, …