Drug Utilization and Potential Drug-Drug Interactions within an Intensive Care Unit at a University Tertiary Care Hospital in Egypt.

There are few reports on drug utilization and drug-drug interactions in Intensive Care Units (ICUs) in Egypt. A total of 94 patients participated in this retrospective observational study. Patient's medical records were used to collect demographics, medical history, admission and discharge dates and medications used. The mean ± SD of the Glasgow Coma Scale (GCS) scores was 9.9 ± 4.4 and the median length of stay was 7 days (range 1-47 days). The total number of prescribed medications ranged from 4-29 with a mean ± SD of 14.1 ± 5.5 medications per patient. The top three most prescribed categories belonged to (1) anti-infective agents (23.9%); (2) electrolyte, caloric and water balance agents (14.6%); and (3) blood formation, coagulation and thrombosis (11.3%). The proton pump inhibitor, esomeprazole, was the most frequently prescribed medication accounting for 6.5% of total prescriptions, followed by clindamycin and magnesium sulfate each accounting for 3.5% of total prescriptions. The potential Drug-Drug Interactions (pDDIs) showed a total of 968 pDDIs with a mean ± SD (range) of 10.2 ± 9.4 (0-43) pDDIs per patient: severe (contraindicated) (3), major (178), moderate (618) and minor (169). Overall, the drug utilization patterns in this study were consistent with ICU drug utilization from other countries in the region. The implementation of clinical decision support systems and the involvement of clinical pharmacists may help improve medication safety.

Performance evaluation of the automated nucleated red blood cell count of five commercial hematological analyzers.

INTRODUCTION: Recent automated hematology analyzers (HAs) can identify and report nucleated red blood cells (NRBC) count as a separate population out of white blood cells (WBC). The aim of this study was to investigate the analytical performances of NRBC enumeration on five top of the range HAs. METHODS: We evaluated the within-run and between-day precision, limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) of XE-2100 and XN-module (Sysmex), ADVIA 2120i (Siemens), BC-6800 (Mindray), and UniCel DxH 800 (Beckman Coulter). Automated NRBC counts were also compared with optical microscopy (OM). RESULTS: The limits of detection for NRBC of the BC-6800, XN-module, XE-2100, UniCel DxH 800, and ADVIA 2120i are 0.035×109 /L, 0.019×109 /L, 0.067×109 /L, 0.038×109 /L, and 0.167×109 /L, respectively. Our data indicated excellent performance in terms of precision. The agreement with OM was excellent for BC-6800, XN-module, and XE-2100 (Bias 0.023, 0.019, and 0.033×109 /L, respectively). ADVIA 2120i displayed a significant constant error and UniCel DxH 800 both proportional and small constant error. CONCLUSION: Regards to NRBC counting, the performances shown by BC-6800, XN-module, and XE-2100 are excellent also a low count, ADVIA 2120i and UniCel DxH 800 need to be improved.

Comparing the performance of three panels rules of blood smear review criteria on an Italian multicenter evaluation.

BACKGROUND: The aims of this study were to compare the diagnostic accuracy of blood smear review criteria, by means of three different panel rules, those proposed by: the International Consensus Group for Hematology [41-ICGH rules], the Italian Survey [IS rules] and the Working Group on Hematology-SIBioC (WGH) consensus rules (WGH rules). METHODS: This study is based on 2707 peripheral blood (PB) samples referred for routine hematological testing to the WGH-associated laboratories displaced all over the Italian territory. The PB samples were processed on seven different hematology analyzers (HAs): Advia 2120i, XE-2100, BC-6800, ABX Pentra, XN-1000, Cell-DYN Sapphire, and DxH800, respectively. All the results provided by the HAs were analyzed through the application of three different blood smear review criteria: that is, the 41-ICGH, IS, and WGH rules. Finally, data were compared with those obtained by optical microscopy (OM), as the current gold standard. RESULTS: The overall the agreement OM classification with ICGH, IS, and WGH panel rules is 0.83, 0.83, and 0.85, respectively. The false negatives are 2.1%, 3.0%, and 2.9%, while false positives are 15.1%, 13.7%, and 11.7%, respectively. All the seven HAs showed variable interinstrument performance, as three different criteria for OM review were adopted on each of them from time to time. CONCLUSION: These results presented show that the customization of validation rules is necessary for enhancing the quality of hematological testing and optimizing workflow.

National performance on door-in to door-out time among patients transferred for primary percutaneous coronary intervention.

BACKGROUND: Delays in treatment time are commonplace for patients with ST-segment elevation acute myocardial infarction who must be transferred to another hospital for percutaneous coronary intervention. Experts have recommended that door-in to door-out (DIDO) time (ie, time from arrival at the first hospital to transfer from that hospital to the percutaneous coronary intervention hospital) should not exceed 30 minutes. We sought to describe national performance in DIDO time using a new measure developed by the Centers for Medicare & Medicaid Services. METHODS: We report national median DIDO time and examine associations with patient characteristics (age, sex, race, contraindication to fibrinolytic therapy, and arrival time) and hospital characteristics (number of beds, geographic region, location [rural or urban], and number of cases reported) using a mixed effects multivariable model. RESULTS: Among 13,776 included patients from 1034 hospitals, only 1343 (9.7%) had a DIDO time within 30 minutes, and DIDO exceeded 90 minutes for 4267 patients (31.0%). Mean estimated times (95% CI) to transfer based on multivariable analysis were 8.9 (5.6-12.2) minutes longer for women, 9.1 (2.7-16.0) minutes longer for African Americans, 6.9 (1.6-11.9) minutes longer for patients with contraindication to fibrinolytic therapy, shorter for all age categories (except >75 years) relative to the category of 18 to 35 years, 15.3 (7.3-23.5) minutes longer for rural hospitals, and 14.4 (6.6-21.3) minutes longer for hospitals with 9 or fewer transfers vs 15 or more in 2009 (all P < .001). CONCLUSION: Among patients presenting to emergency departments and requiring transfer to another facility for percutaneous coronary intervention, the DIDO time rarely met the recommended 30 minutes.

A review of riverine fluxes of hexachlorocyclohexane and DDT to the Azov and Black seas from the former USSR and Russian Federation.

While the Azov and Black seas are subject to anthropogenic pollution to a much higher extent than any other seas, this has been little studied with only a few critical reviews of contaminant fluxes to these seas. Riverine fluxes of the organochlorine pesticides (OCPs) hexachlorocyclohexane (HCH) and DDT to the Azov and Black seas from the former Soviet Union and Russian Federation were thus reviewed for 1986 to 1996. The review was based on official data and data obtained by independent specialists. The amount of HCH used, and the intensity of usage, in these river catchments decreased during the review period. Concurrently, OCP concentrations in the rivers and their fluxes also decreased according to both official and independent data. A comparison of the official and the independent data sets for 1988 revealed significant differences, reflecting the need for more rigorous sampling and analytical protocols for both data sets. According to the OGSNK/GSN data, the flux rates of the five largest rivers were ranked (from largest to smallest) as follows: Don > Dnestr > Danube > Kuban > Dnepro (alpha-HCH); Danube > Don > Dnestr > Dnepro > Kuban (gamma-HCH); Dnestr > Danube > Don > Dnepro-Kuban (DDT+DDE). For rivers with lower annual riverine discharges, the DDT fluxes were surprisingly high (0.43 to 1.49 tonnes a(-1)). According to independent data for 1988 the rankings of the rivers was: Danube > Don > Dnepro > Dnestr > Kuban (alpha-HCH); Danube > Don > Dnestr > Dnepro > Kuban (gamma-HCH); Danube > Dnepro > Dnestr > Don > Kuban (DDT); Danube > Dnepro > Don > Kuban > Dnestr (DDE). The DDT flux estimates for small rivers derived from independent data were 19 to 46 times lower than those calculated using OGSNK/GSN data. According to the independent data, the total riverine OCP transport from the Russian Federation into the Azov Sea from 1988 to 1996 was 1.288 tonnes of gamma-HCH+alpha-HCH and 1.693 tonnes of DDT+DDE while for the Black Sea they were 3.830 tonnes and 5.116 tonnes for gamma-HCH+alpha-HCH and DDT+DDE, respectively.

Heart rate as a predictor of mortality: the MATISS project.

OBJECTIVES: This study sought to verify the independent role of heart rate in the prediction of all-cause, cardiovascular, and noncardiovascular mortality in a low-risk male population. METHODS: In an Italian population-based observational study, heart rate was measured in 2533 men, aged 40 to 69 years, between 1984 and 1993. Data on cardiovascular risk factors were collected according to standardized procedures. Vital status was updated to December 1997. RESULTS: Of 2533 men followed up (representing 24,457 person-years), 393 men died. Age-adjusted death rates for 5 heart rate levels showed increasing trends. The adjusted hazard rate ratios for each heart rate increment were 1.52 (95% confidence interval [CI] = 1.29, 1.78) for all-cause mortality, 1.63 (95% CI = 1.26, 2.10) for cardiovascular mortality, and 1.47 (95% CI = 1.19, 1.80) for noncardiovascular mortality. Relative risks between extreme levels were more than 2-fold for all endpoints considered. CONCLUSIONS: Heart rate is an independent predictor of cardiovascular, noncardiovascular, and total mortality in this Italian middle-aged male population.

[Socioeconomic aspects and cardiovascular risk factors: experience at the Cardiovascular Epidemiologic Observatory]. / Aspetti socio-economici e fattori di rischio cardiovascolare: i'esperienza dell'Osservatorio Epidemiologico Cardiovascolare.

BACKGROUND: Cardiovascular diseases are more frequent among the poorer social classes of the population. Studies including social and economic factors offer useful information when planning the strategy required in primary prevention. The aim of this investigation was to evaluate the association between socio-economic levels and cardiovascular risk factors in 3198 women and 3218 men aged 35-74 years enrolled for a cross sectional study within the Cardiovascular Epidemiologic Observatory, carried out in 1998 to evaluate the distribution of risk factors and the prevalence of cardiovascular risk conditions. METHODS: The level of education was used to determine the socio-economic status; the distribution of the risk factors and the prevalence of risk conditions were analyzed for the different levels of education. Models of logistic regression were used to evaluate the relation between the socio-economic status and obesity, cigarette smoking, hypertension, and hypercholesterolemia. RESULTS: A higher level of education is significantly protective against both obesity and cigarette smoking. With regard to obesity among males compared to those with a university degree the odds ratio increased to 1.6 for those with an upper secondary education diploma (95% confidence interval--CI 1.09-2.51) and to 3.5 for those without any qualification (95% CI 1.97-6.21). Among women the odds ratio increased to 3.2 (95% CI 1.81-5.81) and to 4.8 (95% CI 2.55-8.98) for the same levels of education. With regard to smoking among males compared to those with a university degree the odds ratio increased to 1.4 for those holding an upper secondary education diploma (95% CI 1.07-1.94) and to 2.3 for those without any qualification (95% CI 1.40-3.68). For men living in central or southern Italy, the odds ratio for cigarette smoking increased to 1.3 (95% CI 1.06-1.57) and to 1.5 (95% CI 1.24-1.82) and the odds ratio for hypercholesterolemia decreased to 0.8 (95% CI 0.62-0.95) and to 0.7 (95% CI 0.58-0.89); with regard to women, living in the same geographic areas the odds ratio for obesity increased to 1.3 (95% CI 1.03-1.65) and to 2.3 (95% CI 1.81-2.83). CONCLUSIONS: In primary prevention it is important to focus the attention on obesity and on smoking habits among the poorer social classes.

Hand-grip strength predicts incident disability in non-disabled older men.

OBJECTIVES: To verify if hand-grip performance in older men is a predictor of disability. DESIGN: Population-based prospective study. SETTING: A sample from the Italian rural cohorts of the FINE study (Finland, Italy, Netherlands Elderly), representative of the general population of elderly men surveyed in 1991 and 1995. PARTICIPANTS: 140 men aged 71-91 years who reported no disability in performing activities of daily living (ADLs), instrumental activity of daily living (IADLs) and mobility activities at baseline examination and provided information on their functional status at follow-up 4 years later. MEASUREMENTS: Disability was defined as needing help in performing ADLs, IADLs and mobility. Hand-grip strength was evaluated at baseline by a mechanical dynamometer. RESULTS: After adjusting for potential confounding variables, a lower concentration of high-density lipoprotein cholesterol was the only factor predicting disability in men aged 76 years or younger and only reduced hand-grip strength predicted incident disability in men 77 years or older. CONCLUSION: Poor hand strength as measured by hand-grip is a predictor of disability in older people. The hand-grip test is an easy and inexpensive screening tool to identify elderly people at risk of disability.

HIV p17 enhances lymphocyte proliferation and HIV-1 replication after binding to a human serum factor.

OBJECTIVE: To analyse the role of recombinant HIV-1 protein p17 in the modulation of cell activity. METHODS: Peripheral blood mononuclear cells (PBMC) obtained from healthy donors were cultured in the presence or absence of p17 with mitogens such as phytohaemagglutinin or interleukin-2 and their response assayed by cell proliferation. Cross-linking experiments were employed to investigate the presence of a binding between p17 and factor(s) present in human serum. An immunoenzymatic assay for p24 antigen detection was used to analyse the effect of the addition of exogenous p17 to cultures of PBMC infected with HIV-1 in vitro. RESULTS: Purified recombinant p17 protein at a concentration of 0.25 microg/ml significantly increased the proliferation of preactivated PBMC obtained from healthy donors. This effect was obtained by binding p17 to factor(s) present in human serum and observed on both CD4+ and CD8+ T cells. Recombinant p17 also induced an increased rate of HIV-1 replication, probably due to enhanced T-cell proliferation. The activity of p17 protein was inhibited by anti-p17 antibodies generated by injecting recombinant p17 in rabbits, but not by human antibodies generated during the natural course of HIV infection. CONCLUSION: Characterization of the human factor(s) and identification of the interacting p17 epitope(s) will improve our understanding of the mechanisms used by HIV to efficiently replicate in our organisms.

Lack of polarized type 1 or type 2 cytokine profile in asymptomatic HIV-1-infected patients during a two-year bimonthly follow-up.

The production of type 1 (interferon or IFN-gamma) and type 2 (interleukin or IL-4 and IL-10) cytokines by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) obtained from asymptomatic human immunodeficiency virus-seropositive (HIV+) patients untreated with any antiviral, antibacterial or antimycotic drugs, and from healthy individuals, was evaluated by quantitative ELISA. Patients who were HIV+ were characterized by the absence of abnormal cytokine production. The level of each cytokine differed among individuals in the same group with intersubject variations greater for HIV+ patients than for healthy individuals. The longitudinal evaluation of IFN-gamma, IL-4 and IL-10 production showed intrasubject variations which were particularly marked in HIV+ patients. Accordingly, HIV+ patients and, to a lesser extent, healthy individuals were characterized by a wide spectrum of possible profiles, which were confined to type 0 phenotype. In HIV+ patients no correlation was found between each cytokine level and the number of CD4+ T cells, not even in those with a falling CD4+ T-cell count and clinical symptoms.

Contribution of CD4+, CD8+CD28+, and CD8+CD28- T cells to CD3+ lymphocyte homeostasis during the natural course of HIV-1 infection.

The relationship between the number of circulating CD4+ T cells and the presence of particular CD8+ T cell subsets was analyzed by flow cytometry on PBL from asymptomatic HIV-1-infected patients whose specimens were collected every 2 mo for a total period of 32 mo. Only slight variations were detected in the absolute number of lymphocytes and percentage of CD3+ lymphocytes, whereas both CD4+ and CD8+ T cell subsets showed wide intrapatient variation. Variations in the number of CD8+CD28+ cells paralleled those of the CD4+ T cell subset in each patient tested, while the presence of CD8+CD28- T cells correlated inversely with CD4+ and CD8+CD28+ T cells. These data show that changes in the number of circulating CD4+-and CD8+CD28+ T cells are strongly related to the presence of CD8+CD28- T cells in these patients. Insight into the significance of CD8+CD28- T cell expansion will allow us to understand the mechanisms and significance of the HIV-1- driven change in CD4+CD8+ T cell homeostasis and the basic immunopathology of HIV disease.

Incidence of major coronary heart disease events: the experience of the Project "Community Control of Chronic Diseases".

Data on incidence of first major coronary heart disease (CHD) event have been collected in a population sample studied in the control area, the municipality of Priverno in Central Italy, 100 km South-East of Rome as part of a Community Control Project of Chronic Diseases run in nearby communities. Men and women aged 40-69 years, examined in population screenings, were followed-up for variable periods of time ranging from 1 month to 11 years, after exclusion of those already carrier of a previous major CHD event. A total of 1427 men and 1675 women corresponding to a maximum of 9590 and 11499 person/years respectively were followed-up. Diagnostic criteria were based on a number of different items including history and ECG data, from screening examinations; discharge records from local hospitals; causes of death from death certificates; and information from mail questionnaires. Four hundred and forty-six men and 501 women were considered partially non respondent since they were examined only once, they did not answer the postal questionnaire, although they were surely alive at the end of the observation period. Incidence estimates were based on different denominators, including or excluding these non respondents. The age adjusted lower incidence estimate was of 40.7 per 10000 person/years among men and 19.7 among women; the higher estimate was of 51.3 and 24.4 per 10000 person/years respectively. Rates were higher among men than among women and were increasing with aging. These incidence rates were slightly lower than those reported from other population studies conducted in Italy in the 1970's and the 1980's, but were in line with the hypothesis of a declining incidence paralleling the decline in CHD mortality. These data, including also estimates in women, represent a reference point for the early 1990's of the frequency and distribution of major CHD events.

In-vitro study of the synergy between beta-lactam antibiotics and glycopeptides against enterococci.

The synergy between glycopeptides and beta-lactams was studied using different techniques such as broth macrodilution, killing curves and agar dilution combined with agar diffusion. Two glycopeptide-resistant enterococci isolated from different clinical samples were used. Results showed different effects with significant changes in MICs. Antibacterial activity was related to the concentration of glycopeptide and beta-lactam for Enterococcus faecalis 8253, while for Enterococcus faecium 8072 a paradoxical effect was observed. With this strain, the best synergic effect was detected at teicoplanin concentrations of 1-4 mg/L, but antibacterial activity was reduced at concentrations of 8, 16 and 32 mg/L. No synergic effect was observed with vancomycin. The combination of agar dilution with agar diffusion techniques may constitute a simple method for routine detection of synergic effects between glycopeptides and beta-lactams.

Flow cytometric analysis of activation markers on stimulated T cells and their correlation with cell proliferation.

The expression of activation antigens, namely CD25, CD69, CD71, and HLA-DR on T cells from 15 healthy individuals stimulated with different mitogens and specific antigens was evaluated by immunofluorescence assay and flow cytometric analysis and compared with cell proliferation as a function of [3H]thymidine incorporation. CD69 was the earliest expressed antigen on stimulated cells, while HLA-DR was the latest. Regardless of the stimulus used, lymphocytes expressing CD25 and CD71 were always more numerous than cells expressing CD69 and HLA-DR. Variations in the proportion of CD4+ and CD8+ T cells expressing each activation marker were observed with different antigenic stimuli. The expression of each activation marker showed overall agreement with the [3H]thymidine incorporation assay in discriminating between positive and negative immune response. However, no correlation was observed between the percentage of CD25-, CD69-, CD71-, and HLA-DR-positive T cells and the amount of [3H]thymidine incorporation. Moreover, low doses of mitogens and antigens as well as short time of stimulation were sufficient to induce T cells to express activation antigens but not to proliferate. Our data show that results obtained by flow cytometry and [3H]thymidine incorporation may differ qualitatively, at least under certain conditions; this suggests that the 2 assays are complementary, and when combined, may gives a clearer understanding of events leading to efficient cell-mediated immune response.

Change in cardiovascular risk factors during a 10-year community intervention program.

The study describes changes in cardiovascular risk factors during 10 years of a community intervention program conducted in a rural area in Central Italy. Two areas were involved, one for treatment and one for reference. In 1983-84, 739 men and 859 women in the treatment area and 942 men and 1045 women in the control area, aged 20-69 years, were screened; total and HDL cholesterol, systolic and diastolic blood pressure, fasting blood glucose, smoking habit, weight and height were measured. Between 1983 and 1993 several intervention activities based on community medicine were carried out in the treatment area. They were based on interaction with the local socio-sanitary institutions and school system in order to influence individual persons, small groups and entire community. Major effort was addressed to mass health education, nutrition education, antismoking-propaganda and detection and treatment of hypertension, diabetes and hyperlipidemia.

Heat-killed Bacillus subtilis inhibits T-cell proliferative response to mitogens and recall antigens.

Heat-killed vegetative forms of Bacillus subtilis were found to impair considerably the capacity of human T-lymphocytes to secrete interleukin-2 (IL-2) and to proliferate (in terms of [3H]thymidine incorporation) after phytohaemagglutinin (PHA) stimulation. B. subtilis was also found to interfere with T-cell proliferation induced by concanavalin A (Con A) and the recall antigen tetanus toxoid (TT). The suppressive activity was dependent on bacterial concentration, and was not ascribed to mitogen, medium-nutrient absorption or cell killing. Moreover, B. subtilis did not interfere with mitogen-induced IL-2 receptor expression on the T-cell surface. On the other hand, B. subtilis did not interfere with T-cell proliferation induced by phorbol myristate acetate (PMA) and ionomycin stimulation. All data obtained suggest the binding of B. subtilis subcomponents to- or very close to-the T-cell receptor (TCR). Identification and purification of the basic structure(s) or component(s) of B. subtilis with TCR antagonist activity in vitro will help to exploit different aspects of T-cell activity and development, and possibly, will provide a means of specific control or modification of the immune response.