Effect of hospital-wide interventions to optimize albumin use in a tertiary hospital.

WHAT IS KNOWN AND OBJECTIVE: Albumin has been frequently used as a therapeutic agent based on previous recommendations that are mostly controversial. Considering limited evidence-based indications, common inappropriate albumin use in many hospitals necessitates prompt educational and regulatory interventions. We performed this study to assess the effect of a hospital-wide programme to optimize albumin use in a tertiary referral university-affiliated hospital. METHODS: This study was conducted in three 45-day phases, separated by two sequential interventions: guideline implementation and albumin order-sheet consideration. We evaluated albumin use and assessed its appropriateness in each phase at baseline, after guideline implementation and after order-sheet consideration. RESULTS: We recorded 100, 93 and 71 albumin orders for 100, 84 and 66 patients during the first, second and third phases, respectively. The adjusted number of albumin orders (used albumin vials) was 94.9 (1481.7 vials), 80.8 (1037.6 vials) and 66 (1219 vials) in the first, second and third phases of the study, respectively. Albumin orders with appropriate indication increased significantly over the three phases of the study (OR=1.5, P=.008). The frequency of inappropriate orders reduced significantly from the first phase to the third phase (58%-27%, P=.007). WHAT IS NEW AND CONCLUSION: The pattern and amount of albumin use changed following guideline implementation and order-sheet consideration, and inappropriate albumin use was reduced in our hospital. There was still room for improvement, particularly for indications that were not included in the guideline. Hence, a more comprehensive guideline, frequent audit, feedback and interactive educational approaches might be necessary to achieve results that are of a greater magnitude.

Progesterone downregulates oestrogen-induced expression of CFTR and SLC26A6 proteins and mRNA in rats' uteri.

UNLABELLED: Under progesterone (P) dominance, fluid loss assists uterine closure which is associated with pH reduction. We hypothesize that P inhibits uterine fluid secretion and HCO3⁻ transport. AIM: To investigate the expression of Cystic Fibrosis Transmembrane Regulator (CFTR) and Cl⁻/HCO3⁻ exchanger (SLC26A6) under P effect. METHOD: Uteri from ovariectomized steroid replaced and intact rats at different stages of oestrous cycle were analyzed for changes in protein and mRNA expressions. RESULTS: P inhibits CFTR and SLC26A6 proteins and mRNA expression while oestrogen (E) causes vice versa. E treatment followed by P causes a reduction in these transporters' mRNA and protein. Similar changes occur throughout the oestrous cycle; that is, CFTR mRNA expression was high at proestrus while SLC26A6 mRNA and protein expressions were increased at proestrus and estrus. At diestrus, however, the expression of these transporters' protein and mRNA was reduced. CONCLUSION: Inhibition of CFTR and SLC26A6 expressions may explain the reduced fluid volume and pH under P-mediated effect.

Adverse events induced by ceftriaxone: a 10-year review of reported cases to Iranian Pharmacovigilance Centre.

WHAT IS KNOWN AND OBJECTIVES: Ceftriaxone, a third-generation cephalosporin antibiotic, is used for a vast variety of infectious diseases. Different types of adverse reactions are reported to be induced by ceftriaxone; however, there is limited published information on spontaneous adverse reactions collected by a national pharmacovigilance centre. This study was conducted to evaluate ceftriaxone-induced adverse drug events, registered in the Iranian pharmacovigilance database during a 10-year period, and to identify preventive measures for reducing ceftriaxone-induced adverse events. METHOD: All adverse events registered in the Iranian pharmacovigilance database from 1998 through 2009 were screened for ceftriaxone-related adverse events. The extracted data were categorized based on patients' demographics and previous history of allergic reactions to antibiotics. Assessment of system-organ classes, seriousness and causality of reactions was performed according to World Health Organization scale. The preventability was analysed based on Schumock questionnaire. RESULTS AND DISCUSSION: Ceftriaxone was responsible for the highest number of deaths in our database (49 cases). Of 20,877 reports, 1205 (5·8%) were related to ceftriaxone; 357 reports (30%) are categorized as serious including cardiac arrest, anaphylactic and anaphylactoid reactions. The high number of serious cases makes it necessary to develop preventive measures for reducing those adverse events. Unlabelled use of the drug (2·9%) is identified as one of the risk factors for adverse events. Evaluation of the 1030 intravenous injections of the drug shows that rapid intravenous injection of ceftriaxone is another risk factor. One hundred and sixteen patients (9·6%) had a previous history of allergic reaction to ceftriaxone, penicillin or both. We recommend an alternative antibiotic, if possible, in the case of a positive history of allergic reaction to cephalosporins, penicillins and/or other beta-lactam antibiotics. WHAT IS NEW AND CONCLUSION: Severe and life-threatening adverse reactions induced by ceftriaxone are of great concern. Rapid intravenous injection, unlabelled use and previous patient history of allergic reactions to cephalosporins or penicillins are risk factors that should be guarded against.

Comparison the inflammatory effects of early supplemental parenteral nutrition plus enteral nutrition versus enteral nutrition alone in critically ill patients.

BACKGROUND AND THE PURPOSE OF THE STUDY: It is believed that enteral nutrition (EN) support is the preferred route as compared to parenteral nutrition (PN). Critically ill patients on EN receive less than 60% of their metabolic requirements. To meet patients' calorie goal addition of PN to EN was proposed. This study was conducted to determine whether supplemental PN have any difference with EN alone in regard to inflammatory indices. METHODS: Twenty patients were randomized to either receive EN alone or EN+PN for 7 days. Pre albumin and inflammatory indices including interleukin IL-1, IL-6 and tumor necrosis factor-α (TNF-α) were measured on days of 0, 3,7. Also Sequential Organ Failure Assessment (SOFA) score and Therapeutic Intervention Scoring System-28 (TISS-28) score were calculated on days of 0, 3 and 7. RESULTS AND MAJOR CONCLUSION: IL-1, IL-6 and TNF-α did not show significant difference between two interventions. Pre-albumin was increased from baseline by 9% and 81% in EN and EN+PN groups respectively but it did not reach to statistical significance. SOFA score did not show significant difference. TISS score was higher in EN+PN group on days of 3 and 7. No difference was found between EN and EN+PN regimens in regard to inflammation, while severity of illness may not change with these regimens, nursing workload increases with implementation of supplemental PN.

Sertaconazole 2% cream vs. miconazole 2% cream for cutaneous mycoses: a double-blind clinical trial.

The efficacy of 2% creams of miconazole nitrate and sertaconazole were compared in a double-blind clinical trial carried out on 100 patients with an established diagnosis of cutaneous dermatophytosis. Assessments were performed on days 0, 15, 29 and 43 in our dermatology clinic. Cure was defined according to clinical assessment confirmed by microscopical examination and culture. The groups were similar in age, gender, weight and clinical presentation. The reported side-effects, most commonly pruritus, occurred in 22 (40.0%) and 15 (33.3%) patients in the sertaconazole and miconazole groups, respectively (P = 0.28), but were not serious enough to stop the treatment. The only significant difference between the groups was in per-protocol cure rate by day 15, when patients in the sertaconazole group had a higher cure rate than the miconazole group (P < 0.01). In conclusion, sertaconazole was superior to miconazole in producing an early response in our patients. Given the higher price of sertaconazole and the ability of the considerably less expensive miconazole to produce equally good response after a month, the usefulness of sertaconazole as an alternative to miconazole in Iran requires further study.

Adverse drug reactions in an Iranian department of adult infectious diseases.

This study aimed to assess the frequency and severity of adverse drug reactions (ADRs) (WHO definition) in hospitalized adult patients in an infectious diseases referral ward in Tehran. Of 281 patients evaluated over 6 months, a total of 170 suspected ADRs were reported among 101 patients (35.9%). The most commonly affected organ system was gastrointestinal (47.5%), and the most common class of drugs responsible was anti-infectives (93.1%). ADRs were high among HIV-positive patients (82.9%), mainly due to anti-tuberculosis drugs. Attention to appropriate prescription of drugs is required with more careful clinical and laboratory monitoring of patients.

Estimation of abbreviated mycophenolic acid area under the concentration-time curve during early posttransplant period by limited sampling strategy.

Area under the concentration curve (AUC) of mycophenolic acid (MPA) could help to optimize therapeutic drug monitoring during the early post-renal transplant period. The aim of this study was to develop a limited sampling strategy to estimate an abbreviated MPA AUC within the first month after renal transplantation. In this study we selected 19 patients in the early posttransplant period with normal renal graft function (glomerular filtration rate > 70 mL/min). Plasma MPA concentrations were measured using reverse-phase high-performance liquid chromatography. MPA AUC(0-12h) was calculated using the linear trapezoidal rule. Multiple stepwise regression analysis was used to determine the minimal and convenient time points of MPA levels that could be used to derive model equations best fitted to MPA AUC(0-12h). The regression equation for AUC estimation that gave the best performance was AUC = 14.46 C(10) + 15.547 (r(2) = .882). The validation of the method was performed using the jackknife method. Mean prediction error of this model was not different from zero (P > .05) and had a high root mean square prediction error (8.06). In conclusion, this limited sampling strategy provided an effective approach for therapeutic drug monitoring during the early posttransplant period.

Familiality of cancer in Utah.

The Utah Population Database allows examination of the genetic relationships among the 35.7% of all cancer cases in the state that have genealogical records. Familial clustering of cancer is measured by the Genealogical Index of Familiality and is examined by site, and within site by age of onset, histology, and gender. Most cancer sites examined show excess familiality for all cases considered together. Subsets of individuals with certain characteristics showed unusually high levels of familial clustering, specifically lymphocytic leukemias and especially chronic lymphocytic leukemia, lobular breast cancer, early lip cancer, early melanoma, and female lung cancers of alveolar/adenoma histology. These may represent characteristics of the most penetrant forms of inherited susceptibilities, those which are enhanced by environmental factors, chance aggregations, rare inherited syndromes, or a combination of these factors.

Determination of phenytoin in human plasma by gas chromatography.

A gas chromatographic method for the determination of phenytoin in plasma is described. This assay allows the determination of phenytoin for therapeutic drug monitoring with a minimum detectable limit of 200 ngmL-1 for 500 mL plasma. Separation was performed on 2 m x 2 mm i.d. 1.5% OV17, 1.95 OV210 packed column using a flame-ionization detector. Barbital and tetramethyl ammonium hydroxide were used as internal standard and derivatizing agent, respectively. This method is simple, rapid and suitable for routine analysis of phenytoin in plasma.

N-acetyl cysteine for prevention of oral mucositis in hematopoietic SCT: a double-blind, randomized, placebo-controlled trial.

Oral mucositis (OM) is a complication of high-dose chemotherapy (HDC) which is frequently observed in hematopoietic SCT settings. Antioxidant agents have been proposed to prevent OM and therefore N-acetyl cysteine (NAC) could have an important role. In the present study, we conducted a double-blind, randomized, placebo-controlled study to evaluate the NAC effect on OM incidence and severity, and also glutathione peroxidase-1 activity. Leukemia patients undergoing allogeneic hematopoietic SCT preceded by HDC were recruited into the study and received either NAC (100 mg/kg/day) (n=38) or placebo (n=42) from the starting day of HDC until day +15 after transplantation. OM was evaluated daily for 21 days after transplantation according to World Health Organization oral toxicity scale. The incidence of severe OM (grades 3-4) was significantly lower in the NAC group (23.7% vs 45.3%, P=0.04). Moreover, the mean duration of OM was significantly shorter in the intervention group (6.24(2.96) vs 8.12(3.97) days, P=0.02). The glutathione peroxidase-1 activity was also significantly higher in the NAC group seven days after transplantation (3.38(2.19) vs 2.41(1.70) ng/mL, P=0.003). It is concluded that parenteral NAC is effective in reducing the incidence of severe cases and the total duration of OM.

The efficacy of selenium in prevention of oral mucositis in patients undergoing hematopoietic SCT: a randomized clinical trial.

Oral mucositis (OM) is a complication of high-dose chemotherapy (HDC) followed by hematopoietic SCT (HSCT) with few effective treatments. Selenium has a cytoprotective role via the glutathione peroxidase (Glu.Px) enzyme and prevents chemotherapy-induced toxicities. We performed a double-blind, randomized, placebo-controlled study to evaluate the efficacy of selenium on the prevention of OM in 77 patients with leukemia, undergoing allogeneic HSCT. Thirty-seven patients received oral selenium tablets (200 mcg twice daily) from the starting day of HDC to 14 days after transplantation. OM was evaluated daily for 21 days after transplantation according to World Health Organization oral toxicity scale. The incidence of severe OM (grades 3-4) was significantly lower in the selenium group (10.8% vs 35.1%, P<0.05). We noted that the duration of objective OM (grades 2-4), excluding patient's self-declaration (grade 1), was significantly shorter in the selenium group (3.6±1.84 vs 5.3±2.2 days, P=0.014). Significant elevations in serum selenium level and plasma Glu.Px activity were observed 7 and 14 days after transplantation compared with baseline in the selenium group. We conclude that selenium can reduce the duration and severity of OM after HDC. Clinicaltrial.org ID: NCT01432873.

New guideline for tramadol usage following adverse drug reactions reported to the Iranian Pharmacovigilance Center.

BACKGROUND: Tramadol was introduced as injection and oral form to Iranian Pharmaceutical Market in 2002. Shortly after, the injection form of the drug was observed at the top of suspected drug list of Adverse Drug Reactions (ADRs) received monthly by Iranian Pharmacovigilance Center (IPC). OBJECTIVES: To detect, assess and report total number of Tramadol-induced ADRs received by IPC. To assess the frequency of reported Tramadol-induced ADRs before and after interventions. To design a guideline for prevention of probable ADRs due to Tramadol injection. METHODS: A descriptive study was conducted on spontaneous reporting received by IPC from April 2002 to February 2005. All ADRs suspected to be induced by Tramadol registered in the database during mentioned period were analysed. To assess the effect of different interventions based on Spontaneous Reporting System, the trend of reporting frequency of Tramadol-induced ADRs was evaluated before and after interventions. RESULTS: There were 337 cases of Tramadol-induced ADRs describing 939 reactions, reported to IPC during the study period. Although causal relationship had not been established, three cases of deaths appeared among the reports. The severity of reactions led to implementation of limitations on injectable Tramadol distribution to community pharmacies and the restriction of its use to hospitals only. Since most adverse reactions were dose-dependent, the drug potency of injectable Tramadol available in the country changed from 100 mg to 50 mg. The assessment of ADR reports received by IPC showed that the frequency of adverse reactions registered in the centre was reduced considerably following these interventions. CONCLUSION: Designing a detailed programme by Pharmacovigilance Centres and closely monitoring of newly marketed pharmaceutical products is highly recommended.

Anti-infectives-induced adverse drug reactions in hospitalized patients.

OBJECTIVES: To assess the rate and seriousness of adverse drug reactions (ADRs) attributable to anti-infective agents in hospitalized patients; to estimate the likelihood of experiencing anti-infectives-induced ADRs at different length of drug usage in the hospital; to compare different classes of anti-infectives in inducing ADRs; to determine the impact of age and sex on anti-infectives-induced ADRs. DESIGN: Prospective cohort study. PARTICIPANTS: Patients admitted to the infectious diseases department at a university teaching hospital, on Sunday to Wednesday, over a 9 months period, who received at least one anti-infective agent were eligible to enter the study. MAIN OUTCOME MEASURES: Any suspected noxious and untoward medical events, including laboratory tests abnormalities following anti-infective therapy. METHODS: All patients admitted have received at least one anti-infective drug. Anti-infective agents induced ADRs were detected by interviewing patients and daily chart review. The seriousness, causality, and type of reactions were classified based on World Health Organization (WHO) definitions. Chi-square analysis was performed to assess the influence of sex and age on occurring ADRs. Both Kaplan-Meier and life table method were used to estimate the time to occur the ADR in anti-infective users. To compare the estimated risk of ADRs induced by different classes of anti-infectives, odds ratios were estimated. In all classes of anti-infectives, the odds ratio of each class was estimated with regard to anti-tuberculosis agents, which had the highest prevalence of ADRs. RESULTS: During the study period, 460 patients were entered the study. During the same period, 38 ADRs were recognized of which 20 (42%) were serious. The most recognized ADRs were suspected to be induced by anti-tuberculosis agents (29.8%). However in comparing with anti-tuberculosis agents, anti-fungal agents were associated with the highest ADR rate (odds ratio [OR], 4.21; 95% confidence interval [CI], 1.41-1.256) whereas cephalosporines were associated with the lowest rate, (OR, 0.1; 95%CI, 0.04-0.26). The survival analysis shows that the likelihood of experiencing an ADR was increased at first 14 days of drug therapy. Also Chi-square analysis shows that greater risk of anti-infectives-induced ADRs was observed in women. CONCLUSION: The rate of ADRs induced by anti-infective agents in this study was 8.2%. This is higher than a standard (5%) which has been reported in other studies. This study also shows that some of the classes of anti-infective agents like anti-fungals need more attention.

A linear time algorithm for calculation of multiple pairwise kinship coefficients and the genetic index of familiality.

We present an algorithm that calculates the mean kinship coefficient between all pairs of individuals in a given set relative to a known pedigree. The time required to make the calculations is proportional to the size of the set. The constant of proportionality is determined by the number of generations that the pedigree spans. A simple alteration to the algorithm allows efficient calculation of all pairwise kinship coefficients within a set of individuals.

Factors associated with preventability, predictability, and severity of adverse drug reactions.

OBJECTIVE: To determine the rate of adverse drug reactions (ADRs) in hospitalized patients in an Iranian hospital and to assess factors associated with preventability, predictability, and severity of ADRs. DESIGN AND PARTICIPANTS: A prospective, randomized study was conducted on 370 patients in a hospital at the Tehran Medical Sciences University, from March to December 1996. Patients who experienced at least one ADR (n = 62) were entered into the database. Preventability, predictability, and severity of reactions were determined, based on the available algorithms developed by other investigators. SETTING: A 1200-bed tertiary care university teaching hospital in Tehran, Iran. RESULTS: Approximately 16.8% (n = 62) of the 370 patients who were included in this study had at least one ADR. One hundred two ADRs were reported during this study. Approximately 58.8% of the ADRs (60 reactions) were identified as preventable reactions and 96.1% as predictable reactions. The severity of 9.8% of the ADRs was identified as mild, 86.3% as moderate, 1% as severe, and 2.9% as lethal. The length of hospitalization increased with the severity of the ADRs. Preventable ADRs were more severe than those that were nonpreventable. In addition, the incidence of preventable ADRs increased with the patients' age and caused longer hospitalization than did nonpreventable ones. The most predictable ADRs were hematologic. CONCLUSIONS: This study noted that the rate of ADRs in Iran is probably as high as the rate in other parts of the world. These results indicate a need for a strong national ADR program that detects and reports adverse drug events in Iran.

Comparison of the efficacy and safety of fenofibrate and lovastatin in patients with primary type IIa or IIb hyperlipidaemia.

OBJECTIVES: To evaluate and compare the efficacy and safety of fenofibrate and lovastatin in patients with type IIa or IIb hyperlipidaemia. METHODS: One hundred patients entered this single-centre, open, comparative trial. After 2 months of diet therapy, 33 patients (16 with type IIa and 17 with type IIb hyperlipidaemia) were randomized to treatment for 3 months with a single daily 300 mg dose of fenofibrate or 20 mg of lovastatin. RESULTS: After 3 months of drug therapy, fenofibrate and lovastatin produced significant reductions in levels of total cholesterol and low-density lipoprotein cholesterol in type IIa hyperlipidaemia. In type IIb, the levels of total cholesterol were significantly decreased by both drugs, but only lovastatin significantly reduced low-density lipoprotein cholesterol in these patients. High-density lipoprotein cholesterol levels were significantly increased by lovastatin in type IIa and fenofibrate in type IIb. Fenofibrate decreased total triglyceride levels in both types of hyperlipidaemia significantly more effectively than lovastatin. The most important and commonly observed adverse effects in the fenofibrate group were dermatological events (three patients), myalgia (two patients) and asymptomatic increase in aminotransferase values (nine patients), while in the lovastatin group cardiovascular events (five patients) were the most common. All five patients had coronary heart disease at baseline. In general terms, both drugs were well tolerated. CONCLUSIONS: Comparison between fenofibrate and lovastatin after 3 months of drug therapy in both types IIa and IIb hyperlipidaemia demonstrated that both drugs produced similar reductions in levels of total cholesterol and low-density lipoprotein cholesterol. However, fenofibrate decreased total triglyceride levels in both types of hyperlipidaemia, more effectively than lovastatin. Thus, fenofibrate is suitable for both primary hypercholesterolaemia and combined hyperlipidaemia.

Analysis of discrete phenotypes using a multipoint identity-by-descent method: application to Alzheimer's disease.

The multipoint identity-by-descent method was developed to detect linkage to a specific chromosomal region through partitioning the genetic variance. This method has previously been applied to quantitative traits, and here is extended to a qualitative trait, where a dichotomous affected/unaffected status variable is transformed to a quantitative variable by incorporating covariates. This method is applied to the Alzheimer's disease data sets from Genetic Analysis Workshop 8, to investigate putative linkage to chromosomes 19 and 21. The multipoint identity-by-descent method is used to test for linkage through the qualitative trait, and for excess sharing of the chromosomal region among affected sibs. Results are compared to those of the affected-pedigree-member method and classical linkage analysis. None of these methods gave results showing clear linkage, with the only marginally significant results occurring for the Boston data set on chromosome 19 and the Duke data set for chromosome 21 using the multipoint identity-by-descent method.