Marwan Sheikh-Taha

Comparison between desferrioxamine and combined therapy with desferrioxamine and deferiprone in iron overloaded thalassaemia patients

Summary. Desferrioxamine (DFX) alone (40–50 mg/kg/d s.c. over 8–12 h, five times weekly) was compared with combined DFX twice weekly and deferiprone (75 mg/kg/d) over 12 months in previously poorly chelated thalassaemia patients. Serum ferritin fell from 5506 ± 635 µg/l (mean ± SEM) to 3998 ± 604 µg/l (P < 0·001; n = 14) in the DFX group and from 4153 ± 517 µg/l to 2805 ± 327 µg/l in the combined group (P < 0·01; n = 11). Deferiprone plus DFX produced a greater mean urine iron excretion (1·01 mg/kg/24 h) than iron intake from blood transfusion in each patient. Main side‐effects were skin reactions (DFX alone), nausea and arthralgia (combined therapy). As chelation therapy, the combined protocol was as effective as DFX five times weekly.

Comparison between deferoxamine and deferiprone (L1) in iron‐loaded thalassemia patients

Abstract: Introduction: Iron‐chelating therapy with deferoxamine in patients with thalassemia major has dramatically improved the prognosis of this disease. However, the limitations of this treatment have stimulated the design of alternative orally active iron chelators. Objective: To compare the effectiveness and safety of, and compliance with, oral deferiprone (L1), and deferoxamine, in thalassemia major patients. Methods: All patients were followed up in one center in Lebanon. Sixteen patients were on L1 (75 mg/kg/d), and 40 patients on subcutaneous deferoxamine (20–50 mg/kg/d). Serum ferritin level, urinary iron excretion (UIE) and side effects were monitored over a two year period. Results: Patients on L1 had an initial serum ferritin concentration of 3663±566 µg/l (mean±SEM), that dropped to 2599±314 at 6 months (p<0.02; paired t‐test), and stabilised at that level over the 24 months follow up. Patients on deferoxamine had an initial mean serum ferritin concentration of 3480±417 (NS compared to the L1 group), which dropped gradually to 3143±417 (p<0.05) and 2819±292 (p<0.02) at 6 and 24 months, respectively. The most common adverse reactions associated with L1 were arthralgia and nausea, but they did not necessitate stopping the drug. Conclusion: L1 had comparable efficacy as deferoxamine with minimal side effects and better compliance. Provided long term side effects are not encountered, L1 seems to be a valuable alternative iron chelator for patients unable or unwilling to use deferoxamine effectively.

Absence of cardiac siderosis by MRI T2* despite transfusion burden, hepatic and serum iron overload in Lebanese patients with sickle cell disease

Background:  The use of magnetic resonance imaging (MRI) to detect organ‐specific iron overload is becoming increasingly common. Although hepatic iron overload has been recognized in patients with sickle cell disease (SCD), cardiac iron deposition has only been examined in a few reports.

Safety and Effectiveness of 100 mg/kg/day Deferiprone in Patients with Thalassemia Major: A Two-Year Study

Deferiprone at a dose of 75 mg/kg/day is not sufficiently effective to maintain iron stores at a level which has been considered safe in all patients with iron overload. Our main aim was to determine the safety of long-term therapy with high-dose (100 mg/kg/day) deferiprone. A secondary aim was to determine the efficacy of this high dose. Twelve thalassemia major patients received deferiprone at a dose of100 mg/kg/day over 2 years. Transient aspartate aminotransferase increase (8 patients), gastrointestinal discomfort (3 patients) and arthralgia (2 patients) were the most commonly reported side effects. None of the patients discontinued therapy. The mean serum ferritin level fell from 3,901 ± 3,618 to 1,790 ± 2,205 µg/l after 2 years (p < 0.05). Five of the 12 patients continued to receive deferiprone for an additional 3 years. No new side effects were encountered. The mean serum ferritin level in this subgroup was initially 2,510 ± 332 µg/l and dropped to 1,511 ± 664 µg/l after 5 years (p < 0.05). Liver iron levels at the end of the 2-year study ranged from 1.0 to 30.9 mg/g dry weight, 3 of the patients having levels above 15 mg/g.

Use of acid suppressive therapy in hospitalized non-critically ill patients

AIM To assess the appropriateness of prescribing acid suppressive therapy (AST) in a general medicine service in a tertiary care hospital. METHODS In this retrospective observational study, we reviewed the inpatient records of all patients admitted to the general medical service in a tertiary care hospital in Beirut, Lebanon, from April 1 to May 31, 2011. Treatment with AST was considered appropriate if the patient had a specific indication or appropriate treatment purpose [e.g., gastro-esophageal reflux disease (GERD), peptic ulcer disease, dyspepsia, acute or suspected gastrointestinal (GI) bleeding]. Appropriate administration of stress ulcer prophylaxis (SUP) was derived from an internal guideline that is based on the American Society of Health System Pharmacists guidelines. Prophylaxis was considered appropriate if a patient had 1 absolute indication (coagulopathy or requiring mechanical ventilation), or 2 or more relative indications (sepsis, occult bleeding, use of high dose corticosteroids, recent use of non-steroidal anti-inflammatory drugs for more than 3 mo, renal or liver failure, enteral feeding and anticoagulant use). RESULTS Of the 153 patient admissions during the study period, 130 patients (85%) were started on AST, out of which 11 (8.5%) had a diagnosis that supports the use of this therapy (GI bleed, gastritis and GERD), 16 (12.3%) had an absolute indication for SUP, 59 (45.4%) had 2 or more relative indications for SUP, and 44 (33.8%) received AST without an appropriate indication. In addition, one patient with an absolute indication for SUP and four with two or more relative indications did not receive AST. Rabeprazole was the most frequently used AST (59.2%), followed by omeprazole (24.6%), esomeprazole (11.6%) and ranitidine (4.6%). The dose of AST was appropriate in 126 patients (96.9%) and the route of administration was appropriate in 123 patients (94.6%). Fifteen of the admitted patients (10%) were discharged on AST, 7 of which (47%) did not have an appropriate indication. CONCLUSION AST is overused in hospitalized non-critically ill patients and many patients are discharged on unnecessary AST which can increase cost, drug interactions and adverse events. Potential interventions include implementation of institutional protocols and prescriber education.

Prescription patterns of benzodiazepines in the Lebanese adult population: a cross-sectional study.

This study assessed the profile of benzodiazepine (BDZ) users in Lebanon. Adult patients visiting the pharmacies with prescriptions of BDZs were included in the study. Seven hundred and eighty-six current BDZ users were included, of whom 54.2% were females. Twenty-three percent reported being alcohol consumers and were mostly males. The two most commonly used BDZs were alprazolam (34.6%) and bromazepam (33.6%). The indication for use was mainly anxiety (44.4%), insomnia (22.5%), and depression (15.9%). The prescribing physicians were primarily psychiatrists (43.2%), followed by general practitioners (29.7%). Forty percent had been taking the drug for more than a year. Among those using BDZs for at least 1 month, 35.5% increased the dose with time. Thirty-three percent reported having experienced side effects. Eighteen patients (2.3%) reported taking more than one BDZ concomitantly, while 18.3% were taking drugs that should not be prescribed along with BDZs. In conclusion, the use of BDZs is highest among females, especially for the treatment of anxiety. Moreover, continuous use of the drugs for more than a year as well as significant potential drug interactions was identified.

Effect of age and sex on warfarin dosing

Objective We examined the potential effect of sex and age on warfarin dosing in ambulatory adult patients. Methods We conducted a retrospective chart review of patients attending an anticoagulation clinic. We included patients anticoagulated with warfarin for atrial fibrillation or venous thromboembolism who had a therapeutic international normalized ratio of 2–3 for 2 consecutive months. We excluded patients who had been on any drug that is known to have a major interaction with warfarin, smokers, and heavy alcohol consumers. Out of 340 screened medical records, 96 met the predetermined inclusion criteria. The primary outcome assessed was warfarin total weekly dose (TWD). Results There was a statistically significant difference in the TWD among the ages (P<0.01); older patients required lower doses. However there was no statistically significant difference in the TWD between sexes (P=0.281). Conclusion Age was found to have a significant effect on warfarin dosing. Even though women did require a lower TWD than men, this observation was not statistically significant.

Febrile Neutropenia and Hemorrhagic Stroke in a Thalassemia Major Patient

A 36-year-old transfusion-dependent thalassemia major patient presented with febrile neutropenia and anemia. Deferiprone (L1) was discontinued as it was suspected to be the offending agent and prompt broad-spectrum antibiotic therapy was initiated after which the patient improved. After 11 days the patient developed hemorrhagic stroke and seizure whereby aspirin was discontinued and supportive therapy was given. Agranulocytosis is the most serious complication reported with L1 but, to the best of our knowledge, there are no previous reports on hemorrhagic stroke associated with the use of the agent, and hence, the etiology of the stroke which followed agranulocytosis caused by L1 remains obscure.

Safety and effectiveness of 100 mg-kg-day deferiprone in patients with thalassemia major: A two-year study

Deferiprone at a dose of 75 mg/kg/day is not sufficiently effective to maintain iron stores at a level which has been considered safe in all patients with iron overload. Our main aim was to determine the safety of long-term therapy with high-dose (100 mg/kg/day) deferiprone. A secondary aim was to determine the efficacy of this high dose. Twelve thalassemia major patients received deferiprone at a dose of100 mg/kg/day over 2 years. Transient aspartate aminotransferase increase (8 patients), gastrointestinal discomfort (3 patients) and arthralgia (2 patients) were the most commonly reported side effects. None of the patients discontinued therapy. The mean serum ferritin level fell from 3,901 ± 3,618 to 1,790 ± 2,205 µg/l after 2 years (p < 0.05). Five of the 12 patients continued to receive deferiprone for an additional 3 years. No new side effects were encountered. The mean serum ferritin level in this subgroup was initially 2,510 ± 332 µg/l and dropped to 1,511 ± 664 µg/l after 5 years (p < 0.05). Liver iron levels at the end of the 2-year study ranged from 1.0 to 30.9 mg/g dry weight, 3 of the patients having levels above 15 mg/g.

Patterns of pain medication use in older individuals with cardiovascular disease

Abstract Background: Pain is common in older adults and clinicians are often faced by many challenges when selecting appropriate treatment due to age-related changes in pharmacokinetics, pharmacodynamics, increased comorbidities, and polypharmacy. Methods: This study assessed the patterns of pain medications used at home among older adults admitted to the cardiology service in a tertiary care teaching center in the US from March to May 2016. A retrospective chart review was conducted where adults, 65 years of age or older, with cardiovascular diseases admitted to the cardiology service and taking at least one pain medication at home were studied. Results: Out of 404 patients who were admitted to the cardiology service, 228 (56.4%) were on at least one pain medication. Among the admitted patients, 64.2% of the females received at least one pain medication, as compared to 49% of the males (p = 0.002). Participants had a mean age of 76.34 ± 7.43 years, and received a mean of 1.81 ± 0.83 pain medications. Neuropathic pain was the most common indication (33.4%), followed by arthritis (17.5%), and cancer (15.8%). The most commonly used pain medications were gabapentin/pregabalin 79 (34.6%), acetaminophen plus an opiate 78 (34.2%), opiates 56 (24.6%), tramadol 36 (15.8%), followed by non-selective NSAIDs 21 (9.2%). Twelve (5.3%) patients received duplication of pain medications, while 14 (5.7%) received an inappropriate combination of pain medications. Twenty-three patients (10.1%) received muscle relaxants in conjunction with pain medications, 20 of which are considered poorly tolerated by older adults. Conclusion: This stufy described the patterns of use of pain medications among older adults with cardiovascular disease. Careful selection of appropriate pain medications based on different clinical parameters is very essential to avoid prescribing inappropriate therapy that can lead to patient harm.