Increasing adverse drug reaction reporting-How can we do better?

Adverse drug reactions (ADRs) are associated with morbidity and mortality worldwide. Although national systems for reporting ADRs exist there is a low reporting rate. The aim of the current study was to evaluate an intervention plan for improving ADRs reporting among medical professionals (physicians and nurses). A multicentre intervention study was conducted, in which one medical centre was randomly assigned to the intervention group and two medical centres to the control group. The study consisted of 3 phases: baseline data collection, intervention and follow-up of the reporting rate. The questionnaire that was filled in at base line and at the end of study, contained questions about personal/professional demographic variables, and statements regarding knowledge of and behaviour toward ADRs reporting. The intervention program consisted of posters, lectures, distant electronic learning and reminders. An increase in the number of ADRs reports was noted in the intervention group (74 times higher than in the control group) during the intervention period, which was gradually decreased with as the study progressed (adjusted O.R = 74.1, 95% CI = 21.11-260.1, p<0.001). The changes in the "knowledge related to behaviour" (p = 0.01) and in the "behaviour related to reporting" (p<0.001) score was significantly higher in the intervention group. Specialist physicians and nurses (p<0.001), fulfilling additional positions (p<0.001) and those working in other places (p = 0.05) demonstrated a high rate of report. Lectures were preferable as a method to encourage ADRs reporting. The most convenient reporting tools were telephone and online reporting. Thus, implementation and maintenance of a continuous intervention program, by a pharmacovigilance specialist staff member, will improve ADRs reporting rates.

Low venous thromboembolism incidence in high risk medical patients in an Israeli hospital. Can risk assessment be extrapolated to different populations?

BACKGROUND: Guidelines recommend venous thromboembolism (VTE) prophylaxis in hospitalized medical patients with Padua prediction score (PPS) ≥4 points. This recommendation is based on the high risk of symptomatic VTE observed among these patients in the Italian PPS derivation study, and the fivefold risk reduction with VTE-prophylaxis. This study aims to assess the incidence of VTE in high risk medical patients in a medium sized hospital in Israel. METHOD: In this retrospective cohort study, data was collected of all medical patients hospitalized between January and June 2014. Patients were classified into low and high risk groups according to their PPS score, and according to whether they received anticoagulant thromboprophylaxis for VTE. Patients were further randomly selected to compare high risk patients that did or did not receive anticoagulant thromboprophylaxis. We further compared VTE incidence in high and low risk patients not treated with thromboprophylaxis. A search was conducted for diagnoses of venous thromboembolism and death during hospitalization and the following 90 days. RESULTS: 568 high risk patients (PPS ≥4 points) were included, 284 treated with prophylactic anticoagulation and 284 not. There were no VTE events in either group. There was no difference in mortality. A total of 642 non anticoagulated patients were randomly selected, 474 low risk and 168 high risk. There were no VTE events in either group. CONCLUSIONS: The risk of VTE appears to be very low in our study, suggesting that among medical patients with PPS ≥4, the risk of VTE may differ dramatically between populations.

Does infection prolong the QT interval?

BACKGROUND: The corrected QT (QTc) interval is a strong predictor of ischaemic heart disease and cardiovascular mortality. It may trigger lethal arrhythmias and sudden death. Risk factors include electrolyte disorders, medications, prior cardiovascular disease and genetic predisposition. We previously demonstrated that QTc intervals are prolonged in patients hospitalised with pneumonia, regardless which antibiotics were given. It is unclear whether QTc prolongation is associated with pneumonia itself or whether it occurs with other infections. AIMS: To investigate any association between hospitalisation for infection and QTc prolongation. METHODS: We enrolled 169 patients, 160 of whom were used for analysis. QTc was measured in seconds by routine electrocardiogram (ECG) on admission. Subsequently, daily ECG were performed for 3 days, or until discharge (whichever occurred sooner). When clinically significant QTc prolongation was detected, possible causes were investigated. RESULTS: Clinically significant prolongation was not observed in any patient. The QTc was slightly longer in patients hospitalised for pneumonia or upper respiratory tract infections on admission. It was also prolonged in men, in patients with ischaemic heart disease, hypertension, history of cerebrovascular accident or cancer. A very slight trend for prolongation was observed between the first and second day of monitoring, however it later returned to baseline levels. Nearly 54% of study participants had positive systemic inflammatory response syndrome scores, however no association was detected between their score and baseline QTc, or any subsequent prolongation. CONCLUSIONS: We found no association between hospitalisation due to infection and prolongation of the QTc interval.

Measurement of betamethasone concentration in maternal serum treated for fetal lung maturity; Is it feasible?

BACKGROUND: The association between maternal serum concentration of betamethasone given for fetal lung maturity and perinatal outcome has not been investigated. This may be due to an absence of a reliable method for measuring serum betamethasone concentrations. We aimed in the current study to assess the feasibility of a specific ELISA kit to measure the concentrations of betamethasone in maternal serum and to examine the trend of sequential measurements after a course of betamethasone for fetal lung maturity. METHODS: Pregnant women at risk for preterm birth who received betamethasone between 24 and 34 weeks of gestation were prospectively included. Serum concentrations were determined before administering betamethasone (baseline), and 36 hours, 48 hours, 72 hours, and 5 to 7 days after the 1(st) dose. Betamethasone concentration in samples was determined using Corticosteroid ELISA kit. The Friedman test was used to test whether there were significant differences between the measurements. RESULTS: Five singleton pregnancies were included. Using the ELISA kit, betamethasone concentration in maternal serum samples was obtained for all women. Among the five measurements performed, the concentration was highest at 36 hours after the 1(st) dose and close to baseline at the 5(th) measurement performed after 5 to 7 days (p < 0.05). Serum concentration varied at each time point between the five women but similar trend was observed. CONCLUSION: Betamethasone concentration is measurable in the serum of pregnant women with this ELISA kit.

Intraperitoneal N-acetylcysteine for acute iron intoxication in rats.

Free radical formation and release of oxidant agents have been suggested as possible mechanisms for tissue damage in acute iron intoxication. N-acetylcysteine (NAC), a glutathione substitute and an antioxidant, is widely used as an antidote for various intoxications. Our aim was to determine whether intraperitoneal (i.p.) NAC would reduce the mortality of rats after acute, toxic oral doses of iron. Male Wistar rats were studied in three phases. In the first phase, animals were assigned to groups 1 (distilled water by gavage) and 2 (i.p. NAC) and observed for survival. In the second phase, rats were assigned to groups 3 (400 mg/kg elemental iron orally) and 4 (400 mg/kg elemental iron, followed by 150 mg/kg i.p. NAC). Survival was observed. Because most rats in Group 3 died within 90 minutes after iron administration, a third phase was conducted in order to allow for comparison of iron and transaminase serum levels after the administration of iron and NAC (group 5: n = 10). Mortality was significantly lower in rats treated with iron and NAC, compared to those treated with iron (P = 0.016). Median serum iron level was significantly lower among rats treated with iron and NAC, compared with rats treated with iron alone (P = 0.002). In a rat model of acute iron intoxication, i.p. administration of NAC may decrease serum iron levels and mortality.

Oral N-acetylcysteine has a deleterious effect in acute iron intoxication in rats.

Acute iron intoxication is associated with depletion of reduced glutathione in hepatocytes and changes in the glutathione system enzymes. We hypothesized that treatment with N-acetylcysteine (NAC), a glutathione reducing agent and an antioxidant, would reduce mortality in acute iron intoxication. We used a rat model to test this hypothesis. Male rats were assigned to 4 groups. Group 1 received 400 mg/kg elemental iron by oral gavage, group 2 received the same dose of iron followed by NAC, group 3 received NAC only, whereas group 4 received distilled water. Iron and liver transaminases in the blood, and glutathione system enzymes in the liver and erythrocytes were measured. Mortality in group 2 was significantly higher after 2, 6, and 24 hours compared with group 1 (P < .001). No deaths were observed in groups 3 and 4. Serum iron levels were significantly higher in group 2 rats compared to group 1 rats (P < .001). Hepatic and erythrocyte glutathione system enzymes were significantly lower among rats in group 2 compared to rats in group 1. The administration of NAC probably increased the absorption of iron through the gastrointestinal tract, causing higher serum iron levels with significant hepatic damage. These results indicate that in a rat model of acute iron intoxication, orally administered NAC may increase mortality.

Hepcidin in acute iron toxicity.

BACKGROUND: Hepcidin regulates extracellular iron concentration by inhibiting iron release from macrophages and preventing iron absorption in the intestine. Our objective was to evaluate the expression of hepcidin in the liver in acute iron poisoning in a rat model. METHODS: Male Wistar rats were assigned to group 1, who received 750 mg/kg elemental iron (LD(50)) by gavage, and group 2 (control), who received distilled water. Iron concentrations and liver transaminases were measured in the serum. Hepcidin messenger RNA levels were measured in the liver. RESULTS: Mean serum iron levels, aspartate aminotransferase, alanine aminotransferase, and uric acid were significantly higher in group 1 compared to group 2 (P < .0001, P = .01, P < .0001, and P = 0.0001, respectively). Hepcidin messenger RNA levels in the liver were significantly higher in the study group (P = .005). CONCLUSIONS: In acute iron intoxication, hepcidin expression in the liver significantly increased. Further studies are needed to determine whether hepcidin levels correlate with the severity of the intoxication.

[The treatment of respiratory ailments with essential oils of some aromatic medicinal plants].

In-vitro and clinical studies suggest the therapeutic potential of aromatic herbs in the treatment of respiratory ailments. The pharmacological and clinical activity of Eucalyptus citriodora, Eucalyptus globulus, Mentha piperita, Origanum syriacum, Salvia fruticosa and Rosmarinus officinalis, include anti-inflammatory, anti-bacterial and anti-viral activities. Some of these herbs have direct activity on the respiratory tract, the coughing reflex and the airflow in the nasal tract. This article reviews the evidence on the efficacy and safety of aromatic trees and herbs which grow in Israel, in the scope of the field of otorhinolaryngology.

Fetal exposure to isotretinoin-an international problem.

BACKGROUND: Isotretinoin is a known teratogen. Pregnancy prevention programs aimed at minimizing isotretinoin exposure in pregnancy have been implemented in North America with limited success. OBJECTIVE: To compare the management of fetal risk of isotretinoin in three countries, including information given to women, implementation of contraceptive methods, and pregnancy outcomes. METHODS: Pregnant women exposed to isotretinoin who called teratogen information services (TIS) in Israel, Italy and Canada between July 1998 and October 2006 were interviewed at the time of initial consultation and after the expected day of delivery. RESULTS: Fifty-three pregnant women exposed to isotretinoin contacted the TIS. Only 41% reported using a birth control method. Just one patient reported using two different forms. Forty-five percent of exposed pregnancies were terminated before delivery and 22% delivered healthy babies. Two babies were born with malformations. CONCLUSIONS: Since isotretinoin-exposed pregnancies still occur, there is a need for more effective strategies, which should take into account the cultural differences.

Consumption of herbal remedies and dietary supplements amongst patients hospitalized in medical wards.

AIMS: Herbal remedies may have adverse effects and potentially serious interactions with some commonly prescribed conventional medications. Little is known about consumption of herbal remedies and dietary supplements by hospitalized patients. The aim was to evaluate the rate of consumption and characterize the patients hospitalized in internal medicine departments who consume herbal remedies and dietary supplements. Also, to assess the medical teams' awareness and assess the percentage of patients with possible drug-herb interactions. METHODS: Patients hospitalized in the medical wards of two hospitals in Israel were interviewed about their use of herbal remedies or dietary supplements. The medical records were searched for evidence that the medical team had knowledge of the use of herbal remedies or dietary supplements. RESULTS: Two hundred and ninety-nine hospitalized medical patients were interviewed. Of the participants, 26.8% were herbal or dietary supplement consumers (HC). On multivariate analysis the only variates associated with herbal or dietary supplement consumption were the hospital [odds ratio (OR) 2.97, 95% confidence interval (CI) 1.29, 6.52], income (OR 0.39, 95% CI 0.15, 1.05), smoking habits (OR 0.17, 95% CI 0.05, 0.55) and benign prostatic hypertrophy (OR 4.64, 95% CI 1.3, 16.5). Ninety-four percent of the patients had not been asked specifically of herbal consumption by the medical team. Only 23% of the hospital's medical files of the HC patients had any record of the use of herbal or dietary supplements. Seven possible drug-herbal interactions were encountered (7.1%). The most serious was an interaction between camomile tea and ciclosporin. CONCLUSIONS: Herbal remedy consumption is common amongst patients hospitalized in internal medicine wards and is often overlooked by the medical team. Patients and doctors should be more aware of the possible adverse effects and of the potential of herb-drug interactions.

Acute paralysis following recreational MDMA (Ecstasy) use.

Methylenedioxymethamphetamine (MDMA), commonly known as Ecstasy, is a hallucinogenic compound structurally related to amphetamine. Ecstasy's severe neurological toxicity includes seizures, subarachnoidal hemorrhage, cerebral infarction, intracranial bleeding and cerebral venous thrombosis. We describe the first case of spinal cord damage presenting as acute quadriplegia and respiratory insufficiency in a healthy adolescent following Ecstasy recreational usage.

Bartonella quintana endocarditis in east Africa.

Bartonella quintana endocarditis is characterized by sub-acute evolution and severe valvular damage, and is associated with homelessness, alcoholism, and lice infestation. We present a case of B. quintana endocarditis in an Ethiopian immigrant without known risk factors for disease acquisition. This is the first case of B. quintana endocarditis reported from east Africa.

Serum antioxidant capacity and the risk of contrast medium nephropathy.

INTRODUCTION: The use of contrast medium can result in an acute reduction in renal function. The exact mechanism of this side effect is not yet fully understood. There is accumulating evidence that reactive oxygen species have a role in renal damage. Prophylactic administration of antioxidant drugs could prevent this reduction in renal function. We examined whether there is a correlation between the antioxidant capacity of the serum and the risk of contrast medium nephropathy. METHODS: We studied prospectively 193 patients with normal renal function who underwent cardiac catheterization. Serum haptoglobin, uric acid, albumin and the total antioxidant capacity were measured before the injection of contrast media. Serum urea and creatinine concentrations were measured before angiography and on days 3 and 7 following the procedure. RESULTS: Eleven patients developed mild renal failure. We compared the serum levels of antioxidant compounds of this group with the serum levels of these compounds in patients who did not develop renal damage. No statistical significant difference in the baseline levels of antioxidant species was found between the two groups. CONCLUSIONS: These prospective data indicate that among low-risk patients with normal renal function, baseline levels of antioxidant material did not predict the possible development of contrast medium nephropathy.

Unilateral pulmonary edema: a rare presentation of congestive heart failure.

The authors present a case of an 85-year-old woman known to suffer from severe congestive heart failure who presented with dyspnea and a unilateral infiltrate in the right lung on chest x-ray. Following clinical judgment, she was diagnosed with unilateral pulmonary edema and was treated accordingly, with rapid improvement of symptoms and disappearance of the infiltrate within 12 hours. The patient had been hospitalized many times during the previous years with pulmonary edema affecting both lung fields. Unilateral pulmonary edema is an unusual clinical condition that has been reported as a manifestation of left heart failure, mostly affecting the right lung. The authors emphasize the possible presentation of unilateral pulmonary edema in a patient with heart failure and recurrent bilateral pulmonary edema.

Sweet's syndrome after pneumonectomy.

We report the case of a 38-year-old woman in whom typical skin lesions of Sweet's syndrome developed 2 days after undergoing left pneumonectomy, which was done because of severe bronchiectasis related to remote chemotherapy and radiotherapy given for lung sarcoma at the age of 8 years. Later fever and leukocytosis appeared, and biopsy results of the skin lesions showed neutrophilic infiltration of the dermis compatible with the diagnosis of Sweet's syndrome. Postoperative Sweet's syndrome has been reported only twice in the world literature. These other two cases and possible pathogenic mechanisms are reviewed.

[Contralateral hemothorax: a late complication of subclavian vein catheterization].

Central venous catheterization is extensively used in unstable patients who need hemodynamic monitoring and in patients who require prolonged treatment such as, chemotherapy, antibiotics therapy, parenteral nutrition, or temporary hemodialysis. Subclavian vein catheterization is the preferred approach for hemodialysis, especially as it does not restrict the patient. Most of the complications related to this procedure are insignificant, however, occasionally they may be life threatening and require surgical intervention. We present a case study of a 77-year-old woman suffering from chronic renal failure. A subclavian catheter was inserted, and the patient started hemodialysis. Three weeks later, during hemodialysis, she complained of right upper abdominal and right chest pain. Chest X-ray showed a moderate to large right pleural effusion, with pleurocentesis confirming the presence of hemothorax.

Sweet's syndrome affecting the external auditory canal and tympanic membrane.

We report a patient who developed left ear pain, dry cough, and fever. The external auditory canal was tender, swollen, erythematous and full of debris. Later the patient developed widespread tender and red skin nodules and pustules that subsequently coalesced to form plaques. Identical lesions developed also in the external auditory canal and the tympanic membrane of the affected ear. Skin biopsy showed dermal neutrophilia, compatible with the diagnosis of Sweet's syndrome. Rapid improvement was achieved with prednisone after the failure of antibiotics.