Effectiveness of Short-term Use of Gabapentin as Pre-emptive Analgesia in Reducing Pain after Video Assisted Thoracoscopic Surgery.

Background: Pain control after thoracoscopy is one of the important issues in patient health care. Pre-emptive analgesia can reduce acute postoperative pain and also prevent chronic pain. This study aimed to evaluate the effectiveness of gabapentin (GABA analog) as pre-emptive analgesia in reducing pain and reducing opiate consumption after video-assisted thoracoscopic surgery (VATS) surgery. Materials and Methods: In this study, 67 patients undergoing thoracoscopic surgery were randomly divided into two groups (31 placeboes and 36 gabapentin). Patients received two capsules (300 mg gabapentin capsules or placebo) on the night before surgery and again one hour before surgery. After completion of the operation, all patients were transferred to the recovery. Evaluation of postoperative pain was performed using the visual analog scale (VAS) every 30 minutes and then after 2, 4, 6, 10, 24 hours. If patients had pain (VAS above 3), intravenous morphine was injected to relieve pain and the number of injections and the total dose of morphine administered was recorded. Results: There was no significant difference between the two groups regarding VAS, blood pressure (BP), heart rate (HR), respiratory rate (RR) and saturated oxygen level (SaO2), urea, creatinine, and adverse effects. Conclusion: Preoperative gabapentin administration did not affect postoperative pain reduction, but morphine consumption in the gabapentin group was decreased during the first 24 hours after VATS.

Antibiotic use Evaluation in Hospitalized Pediatric Patients with Respiratory Tract Infections: A Retrospective Chart Review Study.

INTRODUCTION: Respiratory tract infections (RTIs) are a common cause of antibiotic usage in hospitalized pediatric patients. Inappropriate use of antibiotics may lead to the emergence of multidrug-resistant microorganisms and increased treatment costs. OBJECTIVE: This study was designed to assess antibiotic usage in hospitalized pediatric patients with RTIs. METHODS: Medical charts of the patients admitted to the pediatric ward (PW) and pediatric intensive care unit (PICU) of a tertiary respiratory center were reviewed. Patients' demographic and clinical data, including gender, age, weight, history of allergy, length of hospital stay, clinical diagnosis, and prescribed antibiotics (indication, dose, and frequency of administration) were collected. The appropriateness of antibiotic usage was evaluated in each patient according to international guidelines. RESULTS: Two hundred seventy-nine hospitalized patients were included in the study. The most common reason for hospitalization was pneumonia (38%), followed by cystic fibrosis (20.1%) and bronchitis (5%). The most commonly used antimicrobial agents were ceftriaxone, azithromycin, and clindamycin which guideline adherence for their usage was 85.3%, 23.3%, and 47%; respectively. Inappropriate dose selection was the main reason for non-adherence to the guidelines. The adherence rate to RTIs' guidelines (considering all parameters for each patient) was 27.6%. Multivariate logistic regression analysis demonstrated CF and prescription of azithromycin are predictors of guideline non-adherence. CONCLUSION: We found relatively low adherence to international guidelines in our center that could be related to restricted definitions of optimal antibiotic therapy. Despite most patients received logical antimicrobial therapy, actions should be taken into account to reach optimal antibiotic usage.

Metabolism-based Drug-drug Interactions in Patients with Chronic Respiratory Diseases: A Review Focusing on Drugs Affecting the Respiratory System.

BACKGROUND: Chronic respiratory diseases (CRDs) are increasing in prevalence, as reported by the World Health Organization (WHO). Patients with CRDs usually require co-administration of multiple drugs due to the complex pathogenic mechanisms of CRDs and the existence of concomitant diseases. Polypharmacy (co-administration of more than four medications) is the main risk factor of the occurrence of drug-drug interactions (DDIs) that may lead to reducing treatment efficacy and/or increasing adverse effects. METHODS: This literature-based review focuses on metabolism-based DDIs, the most prevalent DDIs responsible for difficulties in therapeutic management in patients with CRDs. RESULTS: Clinically relevant metabolism-based DDIs occur between drugs used for the treatment of respiratory diseases (corticosteroids, orally inhaled bronchodilators, methylxanthines, anti-leukotrienes, antimicrobials, endothelin receptor antagonists, phosphodiesterase inhibitors, antitussives, and antineoplastic agents) and drugs affecting cytochrome P450 (CYP) (inducers and inhibitors). Considering alternative therapies, adjusting medication doses, or monitoring patients during treatment are recommended to prevent the harmful consequences of these interactions. CONCLUSION: Providing information on clinically relevant interactions of drugs more likely prescribed in daily practices of physicians is essential to improve patient safety. A list of known metabolism-based interactions of drugs affecting the respiratory systems should be available for physicians engaged in the treatment of CRDs.

Potential drug-drug interactions in hospitalized pediatric patients with respiratory disorders: a retrospective review of clinically important interactions.

Background Hospitalized pediatric patients are at an increased risk of experiencing potential drug-drug interactions (pDDIs) due to polypharmacy and the unlicensed and off-label administration of drugs. The aim of this study is to characterize clinically significant pDDIs in pediatric patients hospitalized in a tertiary respiratory center. Methods A retrospective analysis of medications prescribed to pediatric patients admitted to the pediatric ward (PW) and pediatric intensive care unit (PICU) of a respiratory referral center was carried out over a six-month period. The pDDIs were identified using the Lexi-Interact database and considered as clinically relevant according to the severity rating as defined in the database. Frequency, drug classes, mechanisms, clinical managements, and risk factors were recorded for these potential interactions. Results Eight hundred and forty-five pDDIs were identified from the analysis of 176 prescriptions. Of the total pDDIs, 10.2% in PW and 14.6% in PICU were classified as clinically significant. Anti-infective agents and central nervous system drugs were the main drug classes involved in clinically significant pDDIs as object and/or precipitant drugs. A higher number of medications [odds ratio (OR): 4.8; 95% confidence interval (CI): 2.0-11.4; p < 0.001] and the existence of a nonrespiratory disease, which led to a respiratory disorder (OR: 3.8; 95% CI: 1.40-10.4; p < 0.05), were the main risk factors associated with an increased incidence of pDDIs. Conclusions A high and similar risk of pDDIs exists in pediatric patients with respiratory disorders hospitalized in PW and PICU. The patients prescribed a higher number of medications and presenting respiratory symptoms induced by a nonrespiratory disease require extra care and monitoring. Pediatricians should be educated about clinically significant DDIs for highly prescribed medications in their settings in order to take preventive measures and safeguard patient safety.

Biological Monitoring of Healthcare Workers Exposed to Antineoplastic Drugs: Urinary Assessment of Cyclophosphamide and Ifosfamide.

Exposure of health care workers to antineoplastic drugs and subsequent adverse health effects is still an open issue. Very little has been studied on the extent of occupational exposure and handling conditions of antineoplastic drugs in Iran. We aimed to determine cyclophosphamide and ifosfamide concentrations in the urine samples of oncology healthcare workers. In addition, we assessed workplace safety controls that are important to decrease occupational exposure. Urinary samples of subject and control groups were collected to measure pre and post-shift cyclophosphamide and ifosfamide concentrations. Prior to sample collection, an occupational toxicologist observed and recorded working safety conditions for the healthcare workers during an eight-week period. Heath care workers were also asked about occurrence of acute adverse health effects. A total number of 425 chemotherapeutic drugs (389.83 g) were prepared during the study. Cyclophosphamide was detected in five pre-shift and nine post-shift urine samples. One pre-shift and four post-shift urine samples were positive for Ifosfamide. The urine samples of control group had no detectable concentrations of cyclophosphamide and ifosfamide. Personal protective equipment usage was not adequate for handling activities. Some adverse health effects reported by oncology personnel confirmed exposure to antineoplastic drugs. High percentage of oncology personnel was exposed to antineoplastic drugs that could be related to the large amount of drug preparations and inadequate safety controls. We recommend training of oncology personnel, implementation of safety controls, and periodic surveillance in order to minimize workplace contamination and occupational exposure to antineoplastic drugs.

Effect of Adding Magnesium Sulphate to Epidural Bupivacaine and Morphine on Post-Thoracotomy Pain Management: A Randomized, Double-Blind, Clinical Trial.

Post-thoracotomy pain is very severe and may cause pulmonary complications. Thoracic epidural analgesia can greatly decrease the pain experience and its consequences. However, finding new methods to decrease the amount of administered opioids is an important issue of research. We aimed to evaluate the effect of adding epidural magnesium sulphate to bupivacaine and morphine on pain control and the amount of opioid consumption after thoracotomy. Eighty patients undergoing thoracotomy at a tertiary cardiothoracic referral centre were enrolled in a randomized, double-blind trial. Patients were randomly allocated to two groups. Bupivacaine (12.5 mg) and morphine (2 mg) were administered epidurally to all patients at the end of operation. Patients in the magnesium (Mg) group received epidural magnesium sulphate (50 mg), and patients in the control (C) group received normal saline as an adjuvant. Visual analogue scale (VAS) score and the amount of morphine consumption were measured during 24 hr post-operation. Thirty-nine patients in the Mg group and 41 patients in the C group completed the study. Patients in the Mg group had significantly less VAS score at recovery time (p < 0.05), 2 hr (p < 0.01) and 4 hr (p < 0.05) after surgery. The patient-controlled analgesia pump was started earlier in the C group than in the Mg group (p < 0.05). The amount of morphine needed in the Mg group was significantly lower than in the C group (5.64 ± 1.69 mg/24 hr versus 8.44 ± 3.98 mg/24 hr; p < 0.001). Pruritus was seen in the C group (9.7%) and absent in the Mg group (p < 0.05). Co-administration of magnesium sulphate with bupivacaine and morphine for thoracic epidural analgesia after thoracotomy leads to a reduction in post-operative pain score and the need for opioid administration.

Important exposure controls for protection against antineoplastic agents: Highlights for oncology health care workers.

BACKGROUND: A great number of antineoplastic drugs (ANPDs) are used globally in cancer treatment. Due to their adverse health effects, occupational exposure to ANPDs is considered a potential health risk to health care workers. OBJECTIVE: The current study aimed to evaluate safe-handling practices of ANPDs, exposure controls, and adverse health implications for health care providers exposed to ANDPs. METHODS: Prevention measures, including engineering, administrative, and work practice controls, as well as personal protective equipment (PPE), were recorded daily through a questionnaire for six weeks. Acute adverse health effects experienced by health care workers were also documented. RESULTS: The implemented exposure controls for preparation, administration, cleaning, and waste disposal were not in accordance with the safe handling guidelines. Central nervous system disorders (26.33%) were the most frequent acute adverse effects reported by health care workers. A significant correlation was found between the number of experienced adverse effects and handling characteristics, including the number of preparations (r = 0.38, p < 0.05), dose, and the number of prepared drugs (r = 0.46, p < 0.01 and 0.39, p < 0.05), and working hours in different locations of oncology setting for six weeks (preparation room: r = 0.38, P < 0.05, treatment room: r = 0.46, P < 0.01, patient room: r = 0.63, P < 0.01, and station: r = 0.68, P < 0.01). CONCLUSIONS: Due to inadequate control measures, oncology health care workers were in danger of exposure to ANPDs and experienced acute adverse health effects. Implementation of appropriate exposure controls is required to prevent occupational exposure to ANPDs.

Surgical Antibiotic Prophylaxis: A Descriptive Study among Thoracic Surgeons.

BACKGROUND: Surgical site infections (SSIs) are common complications following surgeries and increase mortality, morbidity and healthcare costs. The use of antimicrobial prophylaxis is an effective measure to prevent development of SSIs. This study aimed to evaluate the current use of prophylactic antibiotics in thoracic surgeries in Iran. MATERIALS AND METHODS: A descriptive study was conducted among thoracic surgeons in order to assess their knowledge, attitude and practice (KAP) about surgical antibiotic prophylaxis (SAP). A four-section multiple-choice questionnaire was designed and hand-delivered to registered thoracic surgeons. The surgeons' answers were considered correct when they were in accordance to the American Society of Health-System Pharmacist (ASHP) guidelines. RESULTS: Seventy thoracic surgeons were requested to participate in this study and their response rate was 71.4%. Thirty-five (70%) surgeons had good knowledge about appropriate SAP. However, less than half of the respondents were aware of appropriate SAP in case of Ig E-mediated reaction to penicillin and risk of Gram-negative infections. The surgeon's attitude score about the need for local and national guidelines for SAP was 78% and 90%, respectively. Accordance of the physician's practice with ASHP guidelines regarding timing of the first dosage of SAP was acceptable while correct administration of an intraoperative dose was 40% in agreement with the guideline. CONCLUSION: Although thoracic surgeons had a good attitude towards antibiotic prophylaxis guidelines, their knowledge and practice should be improved for proper administration of SAP.

Potential drug-drug interactions in cardiothoracic intensive care unit of a pulmonary teaching hospital.

Little is known about clinically significant drug-drug interactions (DDIs) in respiratory settings. DDIs are more likely to occur in critically ill patients due to complex pharmacotherapy regimens and organ dysfunctions. The aim of this study was to identify the pattern of potential DDIs (pDDIs) occurring in cardiothoracic intensive care unit (ICU) of a pulmonary hospital. A prospective observational study was conducted for 6 months. All pDDIs for admitted patients in cardiothoracic ICU were identified with Lexi-Interact program and assessed by a clinical pharmacologist. The interacting drugs, reliability, mechanisms, potential outcomes, and clinical management were evaluated for severe and contraindicated interactions. The study included 195 patients. Lung cancer (14.9%) was the most common diagnosis followed by tracheal stenosis (14.3%). The rate of pDDIs was 720.5/100 patients. Interactions were more commonly observed in transplant patients. 17.7% of pDDIs were considered as severe and contraindicated interactions. Metabolism (54.8%) and additive (24.2%) interactions were the most frequent mechanisms leading to pDDIs, and azole antifungals and fluoroquinolones were the main drug classes involved. The pattern of pDDIs in cardiothoracic ICU differs from other ICU settings. Specialized epidemiological knowledge of drug interactions may help clinical practitioners to reduce the risk of adverse drug events.

Microbial contamination of single-and multiple-dose vials after opening in a pulmonary teaching hospital

OBJECTIVES: Intravenous therapy is a complex procedure usually requiring the preparation of the medication in the clinical area before administration to the patient. Breaches in aseptic technique may result in microbial contaminations of vials which is a potential cause of different avoidable infections. We aimed to investigate the prevalence and pattern of microbial contamination of single- and multiple-dose vials in the largest pulmonary teaching hospital in Iran. METHODS: In a period of 2 months, opened single- and multiple-dose vials from different wards were sampled by a pharmacist. The name of the medication, ward, labeling of the vials, the date of opening, and storing temperature were recorded for each vial. Remained contents of each vial were cultured using appropriate bacterial and fungal growth media. RESULTS: Microbial contamination was identified in 11 of 205 (5.36%) of vials. The highest contamination rate was 14.28% for vials used in interventional bronchoscopy unit. The most frequent contaminated medication was insulin. Gram-positive bacteria (81.82%) were more significantly involved than gram-negative ones (9.09%) and fungi (9.09%), with the highest frequency for Staphylococcus epidermidis . CONCLUSIONS: Our data demonstrate that repeated use of vials especially if basic sterility measures are disobeyed can cause microbial contamination of administered products to the patients. Infection preventionists are responsible to train health care workers regarding aseptic techniques and apply guidelines for aseptic handling of intravenous solutions.

Vincristine-induced seizure potentiated by itraconazole following RCHOP chemotherapy for diffuse large B-cell lymphoma.

OBJECTIVES: To report the case of a patient with diffuse large B-cell lymphoma (DLBCL) who developed vincristine (VCR)-induced seizure after R-CHOP chemotherapy. CASE SUMMARY: A 22-year-old boy with DLBCL developed generalized tonic clonic seizures following R-CHOP chemotherapy. After receiving the third cycle of chemotherapy, he developed Aspergillus pneumonia; therefore, itraconazole was started 18 days before the administration of cycle 4 of chemotherapy. Seven days after the administration of the fifth doses of vincristine, the patient reported symptoms of gastrointestinal toxicity (abdominal cramps and constipation). Subsequently, he developed three episodes of generalized tonic-clonic seizure which lasted for 2-3 minutes during one day and became unconsciousness. His serum electrolytes were normal with the exception of low serum sodium (128mEq/L). Blood glucose, blood urea nitrogen, the complete blood count, and a cerebrospinal fluid study were also normal. A computed tomography scan of the brain did not show any abnormalities. He had no previous history of convulsion. Occurrence of seizure due to central nervous system invasion of DLBCL was ruled out with a normal cerebrospinal fluid examination, computed tomography scan, and magnetic resonance imaging of the head. Therefore, the patient's neurotoxicity has been attributed to vincristine, the effects of which were likely potentiated by itraconazole therapy. DISCUSSION: Vincristine is a naturally occurring vinca alkaloid used in various chemotherapy regimens. Neurotoxicity is a known and commonly encountered side effect of vincristine. Peripheral neuropathy is the most common form of vincristine neuropathy whereas central effects are rarer. Enhanced VCR neurotoxicities from drug interactions with several azole antifungals such as itraconazole and voriconazole have been reported. Our case represents a drug possible adverse drug effect based on the Naranjo ADR Probability Scale. CONCLUSION: Administration of vincristine in conjunction with azole antifungals should be with caution and after carefully considering the risks and benefits. Also, it is important to rule out other causes of seizure in these patients.

Isoniazid blood levels in patients with pulmonary tuberculosis at a tuberculosis referral center.

BACKGROUND: Serum concentrations of isoniazid (INH) were evaluated in Iranian patients admitted to the Tuberculosis Ward of Masih Daneshvari Hospital, Tehran, Iran. Factors correlated to plasma INH levels were determined. METHODS: Blood samples were obtained 2 h after ingestion of 5 mg/kg INH in 82 patients (1 sample/patient) on days 3-15 of treatment. The following variables were investigated: INH plasma level, duration of therapy, age, sex, weight, dose of INH administered and smoking status. RESULTS: The average (±SD) age and weight of patients were 60.68 ± 18.53 years and 74.96 ± 7.15 kg, respectively. INH concentrations were low in 14.63% and high in 23.17% of the patients (INH reference range: 3-5 µg/ml). Plasma INH was statistically correlated with duration of INH administration (Kendall's rank correlation, r = 0.66, p < 0.001) but not with other variables. CONCLUSION: Based on the result of this study, plasma INH concentrations were not within the therapeutic range for 37.80% of the patients on conventional therapy. Therefore therapeutic drug monitoring may be needed to optimize INH dosage, especially in patients with inadequate clinical response or toxicity to INH.

Protective effect of N-acetylcysteine on antituberculosis drug-induced hepatotoxicity.

INTRODUCTION: Isoniazid, rifampicin, and pyrazinamide, the first-line antituberculosis (anti-TB) drugs, are associated with hepatotoxicity. AIMS AND OBJECTIVES: To study the hepatoprotective effect of N-acetylcysteine (NAC) on liver injury induced by anti-TB drugs. METHODS: A randomized clinical trial was conducted on 60 new TB patients who were aged 60 years or more. Patients were randomized into two groups. In group I (n=32), drug regimen included daily doses of isoniazid, rifampicin, pyrazinamide, and ethambutol. Patients in group II (n=28) were treated with the same regimen and NAC. The patients were followed up for 2 weeks. Liver enzymes and bilirubins were measured at baseline, after 1 and 2 weeks of treatment, and whenever the patients presented with clinical symptoms of hepatotoxicity. RESULTS: The mean+/-SD values of aspartate aminotransferase and alanine aminotransferase were significantly higher in group I than in group II after 1 and 2 weeks of treatment. Hepatotoxicity occurred in 12 patients with (37.5%) group I and none in group II. The mean duration of treatment before the onset of hepatotoxicity was 4.67+/-4.58 days. CONCLUSION: NAC protects against anti-TB drug-induced hepatotoxicity.

Developing an adverse drug reaction reporting system at a teaching hospital.

Adverse drug reactions (ADRs) are a frequent cause for hospitalization and occur often in hospitalized patients. The objective of this study was to establish an ADR reporting and monitoring system at a teaching hospital. The pharmacovigilance unit of Masih Daneshvari hospital was established by a clinical pharmacist and a clinical pharmacologist. Healthcare professionals were encouraged to report any suspected ADRs encountered in in-patients. The incidence, pattern, seriousness, severity and preventability of the reported ADRs were analysed. During the period of 12 months, for 6840 patients, 112 spontaneous reports were received. The most frequently reported reactions were due to anti-infective agents (58.2%). Ceftriaxone accounted for the highest number of the reported ADRs among anti-infective agents. The skin and appendages system was the most frequently affected system (32.5% of all reactions). Seventeen per cent of the ADRs were reported as serious reactions. Although the incidence of ADRs reported by physicians and nurses was found to be low, this programme was useful as a preliminary programme in initiating a culture of ADR reporting among healthcare professionals. Improved communication between the physicians and nurses with the pharmacovigilance centre in the hospital is suggested.

Gene expression profiles in T24 human bladder carcinoma cells by inhibiting an L-type amino acid transporter, LAT1.

Inhibition of LAT1 (L-type amino acid transporter 1) activity in tumor cells could be effective in the inhibition of tumor cell growth by depriving tumor cells of essential amino acids. Because of the high level of expression of LAT1 in tumor cells, LAT1 inhibitors would be useful for anticancer therapy in suppressing tumor growth without affecting normal tissues. In recent years, cDNA microarray technique is useful technology for anticancer drug development. It allows identifying and characterizing new targets for developments in cancer drug therapy through the understanding genes involved in drug action. The present study was designed to investigate gene expression profile induced by LAT1 inhibitor using gene chip technology. Human bladder carcinoma cells (T24 cells) were treated with classical system L inhibitor 2-aminobicyclo-(2, 2, 1)-heptane-2-carboxylic acid (BCH). Gene chip experiment was applied for treated and untreated cells after 3 and 12 h. Two independent experiments with a high degree of concordance identified the altered expression of 151 and 200 genes after 3 and 12 h BCH treatment. Among these genes, 132 and 13 were up-regulated and 19 and 187 were down-regulated by 3 and 12 h BCH treatment respectively. We found that BCH affected the expression of a large number of genes that are related to the control of cell survival and physiologic behaviors. These data are useful for understanding of intracellular signaling of cell growth inhibition induced by LAT1 inhibitors as candidate for anticancer drug therapy.

Investigation of acute lead poisoning on apoptosis in rat hippocampus in vivo.

Despite decades of study, the exact mechanism of action of lead, a potent neurotoxic agent, have not been fully elucidated. One of the suggested mechanism of lead neurotoxicity is apoptotic cell death. The present study sought to examine the effect of acute lead poisoning on apoptosis in rat hippocampus. Two to four and 12-14 week old rats were treated for 7 days with 15 mg/kg daily dose of lead acetate intraperitoneally. Control animals received distilled water. In treated groups, the blood lead levels was increased by about 17-19-folds. Histological study of hippocampus revealed apoptotic cells, using light and electron microscopy. In Western blot analysis, the ratio of Bax/Bcl-2 protein expression in hippocampus was significantly increased compared to controls. In conclusion, the lead induced cell death in hippocampus in vivo may partly be due to apoptosis.