A narrative review on adverse effects of dasatinib with a focus on pharmacotherapy of dasatinib-induced pulmonary toxicities

Chronic myeloid leukemia (CML), a myeloproliferative disorder caused by the over activity of BCR-ABL1 (breakpoint cluster region-Abelson), has been successfully treated by Tyrosine kinase inhibitors (TKIs). While imatinib is known as the first-line treatment of CML, in some cases other TKIs including dasatinib, nilotinib, bosutinib, and ponatinib may be preferred. Dasatinib, a second-generation TKI, inhibits multiple family kinases including BCR-ABL, SRC family kinases, receptor kinases, and TEC family kinases. It is effective against most imatinib-resistant cases except T315Imutation. Despite the superiority of dasatinib in its hematologic and cytogenetic responses in CML compared to imatinib, its potentially harmful pulmonary complications including pleural effusion (PE) and pulmonary arterial hypertension (PAH) may limit its use. Appropriate management of these serious adverse reactions is critical in both improving the quality of life and the outcome of the patient. In this narrative review, we will scrutinize the pulmonary complications of dasatinib and focus on the management of these toxicities.

Determination of antibiotics consumption in Buali-Sina Pediatric Hospital, Sari 2010-2011

Aim: The increasing prevalence of antibiotic-resistant bacteria is a major health-care problem worldwide. WHO recommends DID [daily defined dose/ 100 Inhabitant /day] as a standard tool for measurement of antibiotic consumption. Since there was not any information regarding the antibiotics usage pattern in the north of Iran, the aim of this study was determine this in our centre

Method: This cross-sectional study was performed in Bouali Sina hospital. Using the health information system [HIS] database, records of patients hospitalized during 22 Sep 2010 - 21 Sep 2011. Data of different wards including Neonatal, NICU, PICU, Pediatrics and Pediatric surgery were separately extracted and analyzed. Drug consumption data were expressed as DID. SPSS 16 software was used for statistical analysis. Independent samples t-test was used to compare the quantitative variables

Result: A total of 4619 in-patients records during 1 year of study including 2494 patients in fall and winter and 2125 patients in spring and summer were evaluated. The most hospitalized patients were in Pediatric ward [43.9 %]. The highest DID value were obtained for ceftriaxone [21.7], ampicillin [6.05] and vancomycin [4.7], while the lowest value was for gentamicin [0.01]. In both cold and warm seasons, Ceftriaxone was the most frequent prescribed antibiotic

Conclusion: The rate of antibiotics consumption especially Ceftriaxone in our setting was significantly higher than the other centers. Strategies for more justified administration of antibiotics especially broad-spectrum ones are necessary

Etiologic and epidemiologic pattern of urolithiasis in North Iran; review of 10-year findings

To determine epidemiologic and metabolic characteristics of renal stone in the northern Iran. We prospectively analyzed demographic, clinical and metabolic findings in children less than 16 years old with renal stone revealed by ultrasonography from September 2003 to May 2012. Evaluations included serum and urine measurement of main elements predisposing patients to stone formation. 271 children [160 males] aged 2 months to 16-years [mean 30 months] were evaluated. 91 [33.6%] had a positive family history, abdominal discomfort [18.8%], UTI [11.8%] and hematuria [11.4%] were main presenting features. 45 children were diagnosed accidentally without any specific compliant. Nearly all [99%] stones lay in kidney., 35.1% had metabolic, 10% infective and 4.1% obstructive trends, 110 children had no definable etiology. Hypercalciuria [25.5%] hyperoxaluria [18.4%] and hypocitraturia [18.1%] were more frequent than uricosuria [8.5%] and cystinuria [3.1%]. Metabolic derangement plays significant role in stone formation in our area. Patients should be carefully evaluated considering this point of view

Drug utilization evaluation of vancomycin in a referral infectious center in mazandaran province

DUE [Drug Utilization Evaluation] studies can help identify and correct problems associated with irrational use of drugs. Considering lack of data regarding how rational vancomycin is being used, we evaluated this DUE study in a referral infectious center to evaluate compliance with guidelines in terms of rational use of this valuable antibiotic. This retrospective study was done for 6 months from March to September 2012 at Razi hospital, an educational hospital affiliated to Mazandaran University of Medical Sciences. Data including patients' demographics, vancomycin dose, kidney function assessment, dose adjustments, sampling and culture were collected. Based on the HICPAC [Hospital Infection Control Practices Advisory Committee] and Up-to-date 2012 advices, the concordance of practice with standard guidelines was assessed. One hundred and forty six medical records were reviewed in this study. Fever and shortness of breath were the most common symptoms at the time of initiation of vancomycin. Skin infections, lower respiratory tract infection and septicemia were the most common initial diagnosis of patients. Sampling was done in almost one-third of patients. Most of patient with a specific order were received vancomycin in half an hour. Considering the indication, Vancomycin was administered appropriately in 58 percent of patients. Vancomycin was used irrationally in a great proportion of patients. The main observed drawbacks were empiric use of vancomycin without subsequent adjustment of antimicrobial agent according to culture and sensitivity data and lack of paying enough attention to calculation of creatinine clearance and dosage adjustment

role of Clinical Pharmacists in the improvement of a pharmacovigilance system: a review of the reported adverse drug reactions during 2004-2010 in Mazandaran Province of Iran

Following establishment of Iranian Adverse Drug Reaction [ADR] Monitoring Center in 1997, ADR committees were established in all hospitals of Mazandaran Province of Iran. Clinical pharmacists from Mazandaran University of Medical Sciences have been involved with these committees since 2007. The aim of this study was to compare the results of the pharmacovigilance system before and after active involvement of clinical pharmacists. This study included Yellow Cards filled out by healthcare providers in Mazandaran Province during 2004-2010. Frequency of Adverse Drug Reactions [ADRs], route of administration, reporters, number of reports in each years and damaged organs were focuses. Statistical analysis was performed by SPSS 16 software. P< 0.05 was considered as significant difference. A total of 793 yellow cards were completed during 2004 - 2010. Only 38 ADRs [4.8%] were related to 2004-2007. Most of the reports generated by Nurses [49.3%] followed by Pharmacists and Physicians [P< 0.001]. Forty-one reactions [5.2%] were serious, most related to Ceftriaxone, Desfonac and Vancomycin. Clinical pharmacists' intervention regarding establishing ADR committees in the hospitals improved the output of the pharmacovigilance system, although under-reporting is still a major drawback of spontaneous reporting.

An unreported clindamycin adverse reaction: wrist monoarthritis

Clindamycin is a lincosamide antibiotic which is approved for the treatment of Anaerobic, Streptococcal and Staphylococcal infections. There has been an increased interest in the use of clindamycin since it achieves high intracellular levels in phagocytic cells, high levels in bone and appears to have an antitoxin effect against the toxin elaborating strains of streptococci and staphylococci. Clindamycin is considered as a bacteriostatic antibiotic, while it is bactericidal against some strains of Staphylococci, Streptococci and Anaerobes such as B.fragilis. Its major disadvantage is its propensity to cause antibiotic-associated diarrhea. In spite of expanded use of clindamycin in bone infections, the adverse reactions of this antibiotic are minor. Polyarthritis is a rare adverse effect of this antibiotic. In this case report, we studied a 75-year-old male patient with past history of drop attack and subdural hematoma who developed skull osteomyelitis after the surgery. After two weeks of intravenous antibiotic therapy, wound discharge was stopped and the patient was discharged from the hospital with the maintenance oral antibiotic therapy including clindamycin 300 mg q8 h, ciprofloxacin 500 mg q12 h and rifampin 600 mg fasting. Six days after the beginning of oral antibiotics, right wrist monoarthritis was developed. It was unresponsive to nonsteroidal anti-inflammatory drug and improved after decreased doses of clindamycin. As best as we know, monoarthritis was not reported with clindamycin previously

comparison of selenium concentrations between congestive heart failure patients and healthy volunteers

Selenium [Se] is an essential trace element mainly obtained from seafood, meat, and cereals. Se deficiency has been identified as a major contributing factor in the pathogenesis of certain congestive heart failure [CHF] syndromes. Since there is controversy over the prevalence of Se deficiency among patient with CHF, the aim of this study was to assess the serum Se concentrations in patients with CHF and compared them with the Se status of healthy controls. The study included 77 patients [age, 68.4 +/- 10.4 years old; 40.3% female] and 73 healthy volunteers [64.9 +/- 4.7 years old; 35.6% female]. A complete medical/drug history and physical examination were performed for all patients and healthy volunteers. All patients had symptoms and signs of CHF and had a left ventricular ejection fraction [EF] of < 40% obtained by echocardiography. The Se concentration was assessed by atomic absorption spectrometer with the Graphite Tube Atomizer. The limit of measurement was 5 microg/L. The Se concentrations in CHF patients did not show a significant difference from those of healthy controls [185.9 +/- 781.2 microg/L vs. 123.3 +/- 115.5 microg/L, respectively; p value = 0.499]. There was no correlation between serum Se concentrations and EF in both the normal group and the patients with heart failure [p value = 0.96 and 0.99; r = 0.006 and 0.002 for patients and healthy volunteers, respectively]. In this study, serum Se levels in CHF patients were similar to those of controls and the Se concentrations did not correlate with the degree of left ventricular dysfunction

Serum zinc level in dilated and ischemic cardiomyopathy

Serum trace element alteration has been reported in dilated and ischemic cardiomyopathy. The reports were controversial. We have studied serum Zinc level in cardiomyopathy patients in northern province of Mazandaran and compared them with healthy volunteers. Serum Zinc level was measured in 30 ischemic and 18 dilated cardiomyopathy patients against 27 healthy volunteers. It was measured using atomic absorption spectrophotometry. Statistical analysis was performed using SPSS for Windows version 14 and independent t-test was used for comparing serum Zinc level in ischemic and dilated cardiomyopathy. Pearson correlation and ANOVA tests were used for numeric variables in three different groups. P<0.05was considered as statistically significant. The mean serum Zinc level was 0.97 +/- 0.25, 1.05 +/- 0.27, 1.21 +/- 0.42 mg/L for idiopathic dilated cardiomyopathy, ischemic cardiomyopathy and healthy volunteers respectively. There was no significant difference between three groups. There was also no correlation between echocardiography data and serum Zinc level. This study showed serum Zinc level might not have a role in pathogenesis of ischemic and dilated cardiomyopathy. As intracellular Zinc level play a role in heart subjected to ischemia- reperfusion, measuring intracellular Zinc may give us a better clue about role of Zinc or other trace elements in pathogenesis of cardiomyopathy