In patients treated with cytotoxic drugs granulocytopenia and septicemia are commonly seen. In this 10-year survey 324 blood culture isolates from 184 patients with hematological diseases and septicemia were studied. The distribution of microbiological diagnoses in patients with hematological diseases as well as acute leukemia 1980-1986 was significantly different (p less than 0.01) from an unselected blood culture material from the same period. The differences are mainly seen between Enterobacteriaceae other than Escherichia coli, Pseudomonas aeruginosa and staphylococci. The microbiological spectrum for patients with hematological disease 1987-1989 was also significantly different (p less than 0.05) from the spectrum of the same group of patients 1980-1986 due to higher frequencies of coagulase-negative staphylococci and alpha-streptococci and lower frequency of E. coli in the latter period. 40% of the isolates were gram-positive cocci during the first period and increased to 50% during the second period. The susceptibility testing indicates that trimethoprim/sulfonamide is not as good a choice as ciprofloxacin or norfloxacin for oral antibiotic prophylaxis. For intravenous therapy imipenem/cilastatin or the combinations of an aminoglycoside/piperacillin or aminoglycoside/third generation cephalosporin have advantages over aminoglycoside/trimethoprim/sulfa in combination. However, addition of isoxazolylpenicillin or vancomycin now seems necessary to cover the increasing part of gram-positive bacteria causing septicemia in patients with hematological disease.
Access to new therapies in hospitals depends upon both clinical trial evidence and local Pharmacy and Therapeutics (P&T) committee approval. The process of formulary evaluation by P&T committees is not well-understood.
To describe the formulary decision-making process in Canadian hospitals for cardiovascular medications recently made available on the Canadian market.
Postal survey of hospital pharmacy directors in all Canadian hospitals with more than 50 beds. Target drugs included abciximab, enoxaparin, dalteparin, clopidogrel, eptifibatide and tirofiban.
Of 428 surveys mailed, responses were received from 164 P&T committees representing 350 hospitals for an effective response rate of 82%. While physicians make up the largest proportion of committee membership, pharmacists play an influential role. Information most commonly cited as influencing formulary decisions included published clinical trials (97%), regional guidelines (90%), pharmacoeconomic data (84%), decisions at peer hospitals (73%) and local opinion leaders (60%). However, this information was often not required on formulary applications. Approval timelines varied widely for target medications but there were no regional, hospital or P&T committee characteristics that were independent predictors of early formulary application or approval.
There is wide variability in the time taken for Canadian institutions to adopt new cardiovascular therapies, which is not explained by regional, hospital or P&T committee characteristics. Standardization of the formulary application and evaluation processes, including sharing of information amongst institutions, would lead to broader understanding of the applicable issues, more objectivity and improved efficiency.
The proportion of identifiable causes of familial thrombophilia has increased from 5-10% to 60-70% since the identification of activated protein C resistance (aPCR) in February 1993 by DahlbÃ¤ck et al. A mutation in the factor V gene (G-->A, 1691) leads to the so called Leiden mutation (R 506 Q) that produces a mutated factor V resistant to the catalytic action of activated protein C (aPC), yet normal in its procoagulant properties. This recently identified aPCR is in Nordic populations the most prevalent and well defined genetic defect associated with disease so far described. Its prevalence in the general population ranges from 0% to up to 15% and suggests that a positive genetic selection pressure has been involved. The aPCR phenotype can be assessed in vitro by measurement of the prolongation of the activated partial thromboplastin time in the presence of aPC, whereas the aPCR genotype is studied using polymerase chain reaction searching for the Arg to Gln mutation in the coagulation factor V gene. Some acquired conditions such as the presence of lupus anticoagulants, antiphospholipid antibodies, pregnancy, liver disease and contraceptives may lead into the aPCR phenotype. The aPCR search must be the initial step in the study of a patient with thrombophilia, either inherited or acquired aPCR together with protein C, protein S and antithrombin III explain 60 to 70% of cases of familial thrombophilia.
Activated protein C (APC) resistance, due to a point mutation in the factor V gene (FV:Q506), is a major risk factor for venous thromboembolism. To determine the prevalence of APC resistance in a large series of pregnant women, and to elucidate its obstetric consequences, we performed a prospective study in Malmo, Sweden, comprising 2,480 women enrolled in early pregnancy. The presence of APC resistance (the FV:Q506 allele) was determined. The women were interviewed about their medical histories including venous thromboembolic events (VTE) in relatives. The outcome variables were the VTE rate, intrapartum blood loss, and the prevalence of selected pregnancy complications such as fetal loss, pre-eclampsia. and intrauterine growth retardation. The overall prevalence of APC resistance was 11% (270/2480). The APC-resistant subgroup did not differ significantly from the non-APC-resistant subgroup in terms of pregnancy complications, but was characterized by an 8-fold higher risk of VTE (3/270 vs. 3/2210), a lower rate of profuse intrapartum haemorrhage (3.7% vs. 7.9%) (p = 0.02), and less intrapartum blood loss (340 ml vs. 361 ml) (p = 0.04). Despite the high prevalence of APC resistance in this series of gravidae (11%), its presence was unrelated to adverse pregnancy outcome apart from an 8-fold increased risk of VTE.
OBJECTIVE: To evaluate the efficacy of biochemical tests in diagnosing acute appendicitis. DESIGN: Open prospective study. SETTING: District hospital, Norway. SUBJECTS: 257 patients with suspected acute appendicitis. INTERVENTIONS: Initial diagnostic accuracy of a logistic regression model using available clinical data was compared with results of corresponding models that included an increasing number of inflammatory parameters. MAIN OUTCOME MEASURES: The estimated probabilities of appendicitis in different testing groups were analysed using receiver operating characteristic (ROC) curves. RESULTS: A model including only clinical variables had a mean area under the ROC curve of 0.854. When the total white blood cell count, C-reactive protein concentration, and neutrophil count were added, the model improved significantly to 0.920. CONCLUSION: Biochemical tests are of additional value in a computer model, and the tests should, if used rationally, also provide physicians with important information in the investigation of acute appendicitis.