Evaluation of the Marburg Heart Score and INTERCHEST score compared to current telephone triage for chest pain in out-of-hours primary care.

INTRODUCTION: Chest pain is a common and challenging symptom for telephone triage in urgent primary care. Existing chest-pain-specific risk scores originally developed for diagnostic purposes may outperform current telephone triage protocols. METHODS: This study involved a retrospective, observational cohort of consecutive patients evaluated for chest pain at a large-scale out-of-hours primary care facility in the Netherlands. We evaluated the performance of the Marburg Heart Score (MHS) and INTERCHEST score as stand-alone triage tools and compared them with the current decision support tool, the Netherlands Triage Standard (NTS). The outcomes of interest were: C­statistics, calibration and diagnostic accuracy for optimised thresholds with major events as the reference standard. Major events are a composite of all-cause mortality and both cardiovascular and non-cardiovascular urgent underlying conditions occurring within 6 weeks of initial contact. RESULTS: We included 1433 patients, 57.6% women, with a median age of 55.0 years. Major events occurred in 16.4% (n = 235), of which acute coronary syndrome accounted for 6.8% (n = 98). For predicting major events, C­statistics for the MHS and INTERCHEST score were 0.74 (95% confidence interval: 0.70-0.77) and 0.76 (0.73-0.80), respectively. In comparison, the NTS had a C-statistic of 0.66 (0.62-0.69). All had appropriate calibration. Both scores (at threshold ≥ 2) reduced the number of referrals (with lower false-positive rates) and maintained equal safety compared with the NTS. CONCLUSION: Diagnostic risk stratification scores for chest pain may also improve telephone triage for major events in out-of-hours primary care, by reducing the number of unnecessary referrals without compromising triage safety. Further validation is warranted.

Performance of a simplified HEART score and HEART-GP score for evaluating chest pain in urgent primary care.

BACKGROUND: Chest pain is a common symptom in urgent primary care. The distinction between urgent and non-urgent causes can be challenging. A modified version of the HEART score, in which troponin is omitted ('simplified HEART') or replaced by the so-called 'sense of alarm' (HEART-GP), may aid in risk stratification. METHOD: This study involved a retrospective, observational cohort of consecutive patients evaluated for chest pain at a large-scale, out-of-hours, regional primary care facility in the Netherlands, with 6­week follow-up for major adverse cardiac events (MACEs). The outcome of interest is diagnostic accuracy, including positive predictive value (PPV) and negative predictive value (NPV). RESULTS: We included 664 patients; MACEs occurred in 4.8% (n = 32). For  simplified HEART and HEART-GP, we found C­statistics of 0.86 (95% confidence interval (CI) 0.80-0.91) and 0.90 (95% CI 0.85-0.95), respectively. Optimal diagnostic accuracy was found for a simplified HEART score ≥2 (PPV 9%, NPV 99.7%), HEART-GP score ≥3 (PPV 11%, NPV 99.7%) and HEART-GP score ≥4 (PPV 16%, NPV 99.4%). Physicians referred 157 patients (23.6%) and missed 6 MACEs. A simplified HEART score ≥2 would have picked up 5 cases, at the expense of 332 referrals (50.0%, p < 0.001). A HEART-GP score of ≥3 and ≥4 would have detected 5 and 3 MACEs and led to 293 (44.1%, p < 0.001) and 186 (28.0%, p = 0.18) referrals, respectively. CONCLUSION: HEART-score modifications including the physicians' 'sense of alarm' may be used as a risk stratification tool for chest pain in primary care in the absence of routine access to troponin assays. Further validation is warranted.

[An adolescent with hemolytic anemia and coagulation disorders as manifestation of Wilson's disease, treated with liver transplantation]. / Een adolescent met hemolytische anemie en stollingsstoornissen als uiting van de ziekte van Wilson, behandeld met levertransplantatie.

A 16-year-old woman presented with anaemia, jaundice, vomiting and nosebleed. She had acute hepatic failure and haemolytic anaemia and developed acute respiratory distress syndrome (ARDS). Wilson's disease was diagnosed. After the ARDS resolved the patient underwent a successful orthotopic liver transplantation. Diagnostic combinations for Wilson's disease are ceruloplasmin < 0.2 g/l with Kayser-Fleischer rings, liver copper > 250 micrograms/g (dry weight) with Kayser-Fleischer rings, or homozygosity for a Wilson mutation on the 13th chromosome. In acute liver failure a copper excretion in 24 h-urine above 1 mg is diagnostic for Wilson's disease, while an elevated serum copper concentration makes this diagnosis very likely. Therapeutic options for Wilson's disease are chelation therapy and liver transplantation; in most cases of acute liver failure due to Wilson's disease orthotopic liver transplantation (preceded by albumin dialysis) is indicated. Nazer's index should be used in addition to the regular King's College criteria for liver transplantation indication.

Procoagulant and proinflammatory activity in acute coronary syndromes.

OBJECTIVES: Both the hemostatic and inflammatory system are thought to play a role in the pathogenesis of acute coronary syndromes. However, their respective contribution and interrelationship remain unclear, therefore, we studied the relationship between activation of the coagulation system and proinflammatory activity in ischemic coronary syndromes. METHODS: Thrombin-antithrombin III (TAT), prothrombin fragments F1 + 2, fibrinopeptide A (FPA), interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured in 50 patients with unstable angina (UA), 60 patients with acute myocardial infarction (AMI) and in 50 patients with stable angina (SA). RESULTS: FPA levels were significantly higher in patients with UA and AMI than in patients with SA (p = 0.0015 and p < 0.0001), and were higher in patients with AMI than UA (p = 0.0013). Plasma IL-6 concentrations were significantly higher in patients with UA and AMI than in patients with SA (p = 0.0020 and p < 0.001), and again were higher in AMI than UA (p = 0.001). Interestingly, FPA or IL-6 elevations on admission were found in different patients. In contrast, TAT, F1 + 2 and IL-8 levels were not different between the three groups. CONCLUSIONS: IL-6 and FPA were shown to be independent predictive markers with equal discriminative power to distinguish stable (SA) from unstable (UA + AMI) patients. Moreover, hemostatic and inflammatory markers can be elevated independently in the acute phase of ischemic coronary syndromes.

Modulation of cytokine release and neutrophil function by granulocyte colony-stimulating factor during endotoxemia in humans.

In this double-blind, cross-over, placebo-controlled, randomized study, two groups of eight healthy male volunteers were challenged with endotoxin (4 ng/kg) on two occasions, once in conjunction with placebo and once with granulocyte colony-stimulating factor (G-CSF; 5 microg/kg). In group 1, G-CSF was administered intravenously 2 hours before endotoxin challenge; in group 2, G-CSF was administered subcutaneously 24 hours before endotoxin challenge. In group 1, G-CSF significantly enhanced the release of tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-8, IL-1 receptor antagonist (IL-1ra), and soluble TNF receptors. In group 2, G-CSF significantly reduced IL-8 concentrations and modestly attenuated TNF and IL-6 levels. In this group, IL-1ra and soluble TNF receptors were enhanced by G-CSF pretreatment and lipopolysaccharide (LPS)-induced soluble TNF receptor release was further augmented, whereas LPS-induced IL-1ra concentrations remained unaltered. Both pretreatments with G-CSF increased LPS-induced peripheral neutrophilia; the expression of CD11b, CD18, and CD67; and the release of elastase and lactoferrin. Both pretreatments also down-regulated neutrophil L-selectin expression and prevented the endotoxin-induced pulmonary neutrophil accumulation during the first 2 hours after endotoxin challenge. These data indicate that two different pretreatments with G-CSF result in differential effects on LPS-induced cytokine release but similar effects on LPS-induced neutrophil activation and changes in expression of cell surface molecules. Finally, regardless of the effects of G-CSF on LPS-induced cytokine release, G-CSF blocks LPS-induced pulmonary granulocyte accumulation.

Interleukin 8 released after acute myocardial infarction is mainly bound to erythrocytes.

OBJECTIVE: To determine whether rapid clearance of interleukin 8 (IL-8) from plasma through binding to the erythrocyte chemokine receptor may be responsible for failure to detect IL-8 consistently after acute myocardial infarction. DESIGN: Plasma concentrations of IL-8 were measured at frequent intervals in 43 consecutive patients. In 21 of these, erythrocyte bound IL-8 concentrations were also measured. The influence of infarct size, type of treatment, and the presence of early successful reperfusion on IL-8 release was assessed. RESULTS: Peak IL-8 concentrations in plasma were raised in 31 of the 43 patients (68%). Median plasma IL-8 concentrations were 16.0 pg/ml (range 2.4 to 225.0 pg/ml) six hours after the onset of chest pain. Twelve hours after the onset of symptoms, plasma IL-8 concentrations had already returned to normal in 27 patients. In contrast, in 18 of 21 patients (86%), erythrocyte bound IL-8 concentrations were raised at between 6 and 30 hours, with a median peak value of 59.8 pg/ml (range 19 to 148 pg/ml). No correlation between peak creatine kinase MB and peak IL-8 (plasma or erythrocyte bound) was observed. There was a significant difference in peak plasma IL-8 concentrations between patients who underwent direct PTCA (19.4 pg/ml) and those who received conservative treatment (9.9 pg/ml; p = 0.0206), but no correlation with the presence of early successful reperfusion. CONCLUSIONS: IL-8 is released in plasma after acute myocardial infarction and subsequently binds to red blood cells, resulting in only a transient rise of plasma IL-8 and a more prolonged increase of erythrocyte bound IL-8.

Incidence of resistance to ampicillin, chloramphenicol, kanamycin, tetracycline and trimethoprim of Salmonella strains isolated in The Netherlands during 1975-1980.

From 1975-1980, about 130 000 Salmonella strains isolated from various sources were tested for resistance to ampicillin, chloramphenicol, kanamycin, tetracycline and trimethoprim. Following the ban on incorporation of tetracycline in animal feeds for nutritive purposes, tetracycline resistance in S. typhimurium and S. panama strains of porcine origin dropped from about 90% in 1974 for both species, to about 34% and 1%, respectively, 1980. The incidence of resistance in human strains concurrently decreased from about 80% in 1974 to 25% and 1%, respectively, in 1980. The build-up of multiple resistance in bovine S. dublin and S. typhimurium strains, already started in 1973-74, has continued. Recently, phage type 193 S. typhimurium strains have become predominant and they are invariable resistant to ampicillin, chloramphenicol, tetracycline, kanamycin, neomycin, streptomycin, sulphonamide and trimethoprim. Up to now, type 193 strains were hardly encountered in human patients, but the number of human isolates is slowly increasing. A fairly large number of multiply resistant strains belonging to S. oranienburg, S. schwarzengrund, S. typhimurium and, recently, S. krefeld have been isolated from adoptive children from the Far East.

Side effects of antibiotics.

A review of the side effects of antibiotics in human patients is presented. At least three classes of untoward reactions may be distinguished: development of drug hypersensitivity, toxicological hazards, and microbial effects such as emergence of drug resistance. The intrinsic toxicitiies of the oldest discoveries, penicillin, penicillin and sulphonamides, have turned out to be very low for most animals as well as for man. These agents interfere with specific synthetic pathways in bacteria which are absent in mammals. The antibiotics discovered next (streptomycin and other amino-glycosides; chloramphenicol; tetracyclines) have all been shown to display, under certain circumstances various types of sometimes serious toxicities. As with thalidomide, the nature of their toxic effects had not been predicted by animal experiments. The present set of medically optimum antibiotics has its origin largely in substances with a long medical tradition. They represent the result of close cooperation of medical and scientific men of various disciplines. For the near future it seems unlikely that antimicrobial drugs will enter human and animal environments while yet tainted with any of the unforeseen side effects revealed in the past. Admirable work very recently carried out in the Institute of professor van Genderen shows that he never lost interest in the group of drugs that he so successfully explored when he was still on the staff of the institute where he started his career.

[Reduction of the number of tetracycline-resistant strains of Salmonella in the Netherlands (author's transl)]. / Afname van het aantal tetracycline-resistente Salmonella stammen in Nederland.

Since 1974, tetracycline resistance in salmonellae of human and porcine origin has decreased nation-wide in the Netherlands. This decrease had coincided with the ban on incorporation of tetracycline in animal feeds for growth-promotion.

Decrease of drug resistance in Salmonella in the Netherlands.

Since 1974, tetracycline resistance in salmonellae of human and porcine origin has decreased nation-wide in The Netherlands. This decrease has coincided with the ban on incorporation of tetracycline in animal feeds.

Incidence of resistance to ampicillin, chloramphenicol, kanamycin and tetracycline among Salmonella species isolated in the Netherlands in 1972, 1973 and 1974.

The resistance of Salmonellae to drugs has been studied in the Netherlands since 1958. In 1972, 1973, and 1974 respectively, 14241, 13086, and 22927 strains were tested for resistance to ampicillin, chloramphenicol, kanamycin and tetracycline. From 1973 all strains were also tested for resistance to trimethoprim. In the period covered, the yearly incidence of resistance to at least one of the above drugs ranged from 39.2% to 45.6% of all strains obtained from various sources (humans, animals, animal products, sewage, etc.). A new finding in the period 1972 to 1974 was that many multiply resistant strains emerged in S. typhimurium and in S. dublin isolated from calves and cattle. In 1974, 64.4% of all strains of S. typhimurium from these animals appeared to be resistant to ampicillin, tetracycline, chloramphenicol and kanamycin, and 25.5% of those of S. dublin were found to be resistant to chloramphenicol and tetracycline. Of all strains of Salmonellae examined in 1973 and 1974 respectively, 0.15% and 0.22% were resistant to trimethoprim, the main component of the twin-drug cotrimoxazol. Of the 142 strains of S. typhi isolated in 1972 to 1974 two were resistant to tetracycline only, and one was resistant to all four antibiotics. The others had a normal susceptibility pattern.

An eleven-year study of drug resistance in Salmonella in the Netherlands.

From 1959 to 1969 a total of 123 070 strains of salmonellae, representing nearly all the strains that have been isolated from animals and man, were collected in the Netherlands and tested for antibiotic resistance.In the course of the study, only a few strains of S. typhi and S. paratyphi B were found to be resistant to chloramphenicol, ampicillin, or tetracycline.From 1959 to 1966 there was a sharp increase in the prevalence of tetracycline resistance in both the human and the animal strains of S. typhimurium and S. panama; subsequently, however, the prevalence declined. During 1966-70 approximately one-third of the tetracycline-resistant human and animal strains of S. typhimurium were also resistant to ampicillin. This type of multiple resistance was only occasionally encountered in the other serotypes. In contrast to resistance to tetracycline and ampicillin, the incidence of S. typhimurium resistant to chloramphenicol remained low during the whole period of observation. In all other serotypes drug resistance remained at a low level.It is shown in this study that the greatly increased use of broad-spectrum antibiotics for medical and veterinary purposes and for animal feeding over the last decade in the Netherlands has not led to the development of serious drug resistance from the medical point of view. An important factor involved in the low incidence of resistance to chloramphenicol may be that R-factors in salmonellae usually lose this resistance determinant rapidly.In the Netherlands the annual mortality figures for all forms of salmonellosis decreased from 0.84 (per 100 000 inhabitants) in 1961 to 0.25 in 1969.