Decolonization of methicillin-resistant Staphylococcus aureus using oral vancomycin and topical mupirocin.

The objective of this study was to assess the efficacy and safety of a short course of oral vancomycin and intranasal mupirocin ointment in the eradication of methicillin-resistant Staphylococcus aureus (MRSA) colonization. During an outbreak of MRSA, the colonized subjects received oral vancomycin and topical mupirocin. They were screened for MRSA 1, 3, 6 and 12 months after decolonization. A questionnaire was developed to evaluate the side-effects of oral vancomycin. Thirty-five subjects were treated. Clearance was achieved in all cases, in 24 (69%) subjects after one course of therapy. Twenty-eight (80%) subjects experienced some side-effects, including six (17%) who did not tolerate oral vancomycin. Although oral vancomycin, in combination with topical mupirocin, is effective in the elimination of MRSA colonization, there is a need for further studies to confirm our results and to evaluate the safety of oral vancomycin.

The influence of extracorporeal clearance techniques on elimination of radiocesium after internal contamination.

Radiocesium, an isotope released after nuclear accidents such as Chernobyl, causes damage to the health of humans after internal contamination. As a result of an internal deposit of radiocesium these persons are continuously irradiated and noxious effects may occur. Removal of this internal radiation source will reduce immediate (short-term) and future damage (long-term). In order to obtain data with respect to cesium kinetics in vivo, data obtained in dogs by Nold et al. were fitted by a computer program. On the basis of these data, simulations were carried out to evaluate the influences of extracorporeal clearance on cesium kinetics. The influence of various treatments on the committed effective dose [E(50)] as a measure of radiation harm was simulated. For this purpose an equivalence between the committed effective dose and the area under the curve, a kinetic parameter, was derived. This equivalence only holds when comparisons are made for different treatments of one subject contaminated with one isotope. Treatment with orally administered Prussian Blue salts reduces the committed effective dose by 29% (50 y). This can be insufficient to prevent deterministic effects as a result of a severe internal contamination with radiocesium. For this purpose other methods are evaluated. In simulations, extracorporeal clearance (e.g. hemoperfusion or hemodialysis) proved to be more effective in reducing E(50) (> 50%, 50 y). Extracorporeal clearance also seems to be effective in the early dose reduction and its consequent deterministic effects. Simulations revealed that effectiveness is improved when the treatment is started earlier and continued for a longer period. Effective extracorporeal clearance may be considered to be a promising method to treat victims of nuclear accidents internally contaminated with radiocesium.

Hemodialysis as a potential method for the decontamination of persons exposed to radiocesium.

Radiocesium may be deposited in the environment as a result of accidents in nuclear installations, for example, as in Chernobyl. Significant internal contamination with radiocesium poses a serious risk to human health, and, therefore, expedient removal is essential to reduce the radiation body burden. In vitro hemodialysis was tested as a potential method to remove radiocesium from a pasteurized plasma solution of bovine or human blood. Clearance values were calculated by a flow independent method. Hemodialysis appears to be a good method to remove radiocesium from blood: within 4 h more than 90% of the administered radiocesium is removed from blood or plasma. Radiocesium in dialysis fluid can be concentrated on Prussian Blue coated columns that were tested previously for hemoperfusion. Radioactive waste disposal problems can be solved by concentration of radiocesium on these columns. In vivo experiments are necessary to confirm these in vitro results.

An added value for the hemoglobin content in reticulocytes (CHr) and the mean corpuscular volume (MCV) in the diagnosis of iron deficiency in postpartum anemic women.

INTRODUCTION: To evaluate the use of reticulocyte hemoglobin content (CHr) and mean corpuscular volume (MCV) to identify truly iron-deficient women with postpartum anemia (PPA), in order to reduce unnecessary iron supplementation. METHODS: Three hundred women with more than 500 mL of blood loss or clinical signs of anemia were divided in a control (Hb ≥ 10.5 g/dL, N = 150) and postpartum anemia group (PPA, Hb < 10.5 g/dL; N = 150). PPA women were given ferrous fumarate for a period of 4 weeks. Efficacy of the treatment was evaluated by comparing Hb, CHr, and MCV at baseline (T(0)) and after 4 weeks (T(4)). Using standard iron deficiency cut off values for MCV (80 fL) and CHr (28 pg) at T(0), we divided the PPA group of both parameters into two subgroups, one suggestive for iron deficiency and one suggestive for noniron deficiency. RESULTS: Irrespective of the parameter or the subdivision, delta Hb concentrations (T(4) -T(0)) showed a similar increase in all PPA subgroups investigated. Both parameters in the PPA subgroups below their respective cut off value showed a significant improvement toward normalization, while the MCV and CHr in the PPA subgroups above their respective cut off value did not show any significant increase. CONCLUSION: Our data suggest that the etiology of the anemia in postpartum anemic women is not always iron deficiency. Using a combination of Hb, MCV and CHr, we increased the stringency to identify truly iron-deficient postpartum anemic women, thereby reducing unnecessary iron supplementation in those women with sufficient iron stores.

In vitro binding of radiocesium to Prussian Blue coated strips and Prussian Blue containing hemoperfusion columns as a potential tool for the treatment of persons internally contaminated with radiocesium.

Cellulose or nylon strips coated with three different Prussian Blue salts were prepared with cellulose nitrate as binding material. These strips were evaluated for their usefulness for the development of an extracorporal clearance device for radiocesium, a radionuclide often released after accidents in nuclear installations (for example in Chernobyl). Extracorporeal clearance can be used to enhance the elimination of radiocesium from internally contaminated persons. The stability of these strips and their binding characteristics for radiocesium were investigated. In all studies strips coated with Fe4[Fe(CN)6]3 proved to be the most suitable for further development of an extracorporeal clearance device: the strips are stable, have a high binding capacity for radiocesium, and can be sterilized. On the basis of these results, hemoperfusion colums containing Fe4[Fe(CN)6]3-coated strips were developed and tested. In in vitro experiments these columns proved to be successful in removing radiocesium from a pasteurized plasma solution (clearance was approximately 100 ml/min). The binding capacity of these columns is relatively high. In 4 h the columns are able to bind approximately 0.3 TBq of radiocesium. They are a promising development for the enhancement of the removal of radiocesium from the human body. They can also be used for the decontamination of other fluids of chemical or biological origin. Further research is, however, still necessary.

In vitro cyanide release of four prussian blue salts used for the treatment of cesium contaminated persons.

Prussian blue salts are used in clinical practice as an antidote for the treatment of humans contaminated with radioactive cesium. A decomposition product of these Prussian blue salts may be the highly toxic cyanide. A method to simulate gastrointestinal cyanide-release was applied to four different Prussian blue salts: K3Fe[Fe(CN)6], Fe4[Fe(CN)6]3, NH4Fe[Fe(CN)6] (pur. and unpur.). Cyanide-release was higher in artificial gastric juice than in water and artificial intestinal juice. Under all conditions cyanide-release from Fe4[Fe(CN)6]3 was the lowest. Since Fe4[Fe(CN)6]3 also binds more cesium, it appears to be the most suitable Prussian blue salt for use as an antidote after radiocesium contamination in humans.

In vitro binding characteristics for cesium of two qualities of prussian blue, activated charcoal and Resonium-A.

The in vitro binding characteristics of radioactive 137Cs to two forms of Prussian blue [colloidally (soluble) K3Fe[Fe(CN)6] and insoluble Fe4[Fe(CN)6]3] and to activated charcoal and sodium polystyrene sulfonate (Resonium-A) were investigated by constructing Langmuir isotherms at pH = 1.0, 6.5 and 7.5 at 37 degrees C. At the three pHs investigated, 137Cs binding to activated charcoal and sodium polystyrene sulfonate was negligible. Binding of 137Cs to insoluble Prussian blue exceeded that for the soluble form and was pH dependent for both formulations. Maximum binding capacities were 87 mg/g (pH = 1.0), 194 mg/g (pH = 6.5) and 238 mg/g (pH = 7.5) for the insoluble form and 48 (pH = 1.0), 73 (pH = 6.5) and 78 (pH = 7.5) for the soluble form. As activated charcoal did not bind 137Cs, charcoal hemoperfusion is of no value. This has been confirmed by an in vitro experiment, using a Gambro Adsorbs 300 C cartridge.

Risk factors for the development of adverse drug events in hospitalized patients.

Adverse drug events in hospitalized patients lead to increased morbidity, mortality and costs. Early detection of adverse drug events could aid in the prevention of these adverse outcomes. A cost-effective system for the early detection of adverse drug events should focus on high risk patients. A study was set up with the primary aim to identify characteristics that are associated with the development of adverse drug events (ADEs) in hospitalized patients. ADE reports were gathered from physicians and nurses (spontaneous reports) and from patients after intensive ward interviews by hospital pharmacists. All patients admitted to the internal medicine wards of two Dutch hospitals, during a two month period, were included. The following characteristics were analyzed for their potential relationship to the occurrence of ADEs: age (categorized), gender, number of drugs prescribed during hospital stay, types of drugs used and changes in drug use on admission. Age was found to be inversely associated with the development of ADEs (OR 0.36, CI 0.21-0.61 for age category > 80 years; OR 0.56; CI 0.31-1.02 for age category 75-80 years and OR 0.69; CI 0.42-1.11 for age category 60-74 years). Furthermore, statistically significant associations were found for the number of drugs prescribed per hospitalized patient (for the class of 4-6 drugs per patient OR 2.61, CI 1.32-5.18), for newly prescribed drugs (OR 6.65, CI 2.63-16.81) and for the cessation of drugs on hospital admission (OR 1.50, CI 1.02-2.20). The use of gastrointestinal drugs (OR 2.13, CI 1.32-3.45), central nervous system drugs (OR 1.66, CI 1.07-2.57) and antibiotics (OR 2.44, CI 1.65-3.60) were associated with the development of ADEs, when compared to all other drugs taken by the patients. In this study, the most important risk factors are the number of drugs used per patient and the starting of a new drug during hospitalization. As most hospitalized patients start new drug therapies while in hospital, this seems an inappropriate focus. However, careful monitoring of patients using more than 7 drugs at a time may be possible in a cost-effective system for the early detection of ADEs.

Incidence of discontinuation of highly active antiretroviral combination therapy (HAART) and its determinants.

OBJECTIVE: To determine the incidence and determinants for discontinuation of initial highly active antiretroviral therapy (HAART). DESIGN: In this retrospective follow-up study from hospital files and pharmacy dispensing data, a standard dataset was collected including patient characteristics, therapy characteristics, and HIV-monitoring parameters (e.g., CD4+ lymphocyte counts, viral load determinations). Kaplan-Meier estimates of the cumulative probability of discontinuation of initial HAART were calculated. Cox proportional hazard analysis was used to identify determinants for discontinuation of initial HAART. PATIENTS: All patients starting HAART (n = 99) during June 1996 to February 1997 at our regional AIDS center. MAIN OUTCOME MEASURES: Incidence and determinants for discontinuation of HAART. RESULTS: During the mean follow-up of 450+/-10 days, 27 patients switched initial HAART, 3 patients stopped any antiretroviral therapy. Reasons for switching were increasing viral load (18x), insufficient decrease of viral load (3x), and adverse events (6x). Nonnaivete for antiretroviral therapy and a lower CD4+ lymphocyte count at start were identified as determinants for discontinuation of initial HAART. CONCLUSIONS: The overall incidence density for discontinuation of initial HAART was 25 per 100 patients/year. The main reason for switching was an increasing viral load. CD4+ lymphocyte counts at start and nonnaivete for antiretroviral therapy were identified as determinants for discontinuation.

Adverse drug events in hospitalized patients. A comparison of doctors, nurses and patients as sources of reports.

OBJECTIVE: This study investigated the relative value of adverse drug events reported by doctors, nurses and patients. METHODS: The study was conducted on a total of four wards: the paediatric and internal medicine wards (including geriatric patients) of two peripheral hospitals in The Netherlands. Adverse drug events were collected by spontaneous reporting (doctor and nurse reports) and by daily ward visits, during which the patients were interviewed by a hospital pharmacist (patient reports). Criteria for relative value of the reported adverse drug events were the number of potentially serious reactions, the number of reactions not mentioned in the patient information leaflet and the number of reactions reported to new drugs (5 years or less on the Dutch market). No formal causality assessment was applied. RESULTS: Over a period of 2 months in 1996 (Hospital I) and 2 months in 1997 (Hospital II) a total of 620 patients were included in the study and adverse drug events were reported in 179 (29%) of these cases. Doctors reported a statistically significant larger number of serious (26% of all doctor reports; odds ratio (OR) 3.2; confidence interval (CI) 1.2-8.7) and unknown (39%; OR 2.5; CI 1.0-6.0) adverse drug events than patients themselves during the daily ward visit. Doctors also reported more serious and unknown adverse drug events than nurses. Adverse reactions to new drugs were reported during the daily ward visit only (8% of all daily ward visit reports). CONCLUSION: This study reconfirms that doctors are the main source for reports of serious and unknown adverse drug events in hospitalized patients. However, patients themselves seem to report more adverse reactions to new drugs (during the daily ward visit). By focusing on patients using new drugs, the daily ward visit might become cost-effective. This needs to be explored in future studies.