Ginkgo biloba Efficacy in the Treatment of Drug-Induced Parkinsonism: A Randomized Clinical Trial.

Background: Drug-induced parkinsonism (DIP) is one of the most common movement disorders in approximately 20 - 35% of patients on antipsychotic medications. Managing the symptoms of DIP is challenging due to the limited number of potentially effective medications. On the other hand, this restricted possible treatment could have numerous side effects that ultimately result in patients stopping the medication all at once. The neuroprotective property of Ginkgo biloba extract (EGb) emerged as an effective commodity for the additional treatment of psychiatric disorders. Objectives: This study aimed to evaluate the efficacy of EGb in psychiatric patients with symptoms of DIP. Methods: A sample of 63 patients who met the inclusion criteria were recruited and randomly assigned to control and experimental groups. Both groups were followed for 3 months. One group received 80 mg of G. biloba three times a day, and the control group received a placebo. The patients were evaluated using the Unified Parkinson's Disease Rating Scale and Montreal Cognitive Assessment. Results: Ginkgo could change the intensity of rest tremors, the severity of motor symptoms, rigidity, and bradykinesia. Ginkgo biloba might alleviate the severity of parkinsonism and motor symptoms and could lead to changes in the two components of working memory and short-term memory. Conclusions: Ginkgo biloba extract can be used as an effective and safe treatment in the management of DIP, whether in patients diagnosed with psychotic disorders or mood disorders.

A nationwide study on consumption of opioid analgesics in Iran from 2000 to 2018.

BACKGROUND: Opioid analgesics play a unique role in pain management. National opioid consumption studies could provide indirect evidence of pain management in a country. National, regional, and global opioid consumption have been studied in other countries so far; however, conducting a focused study to illuminate the consumption of opioid analgesics over the past decades in Iran seemed necessary. AIM: The main objective of this study was to determine the consumption of opioid analgesics and explore the trend of their use during 19 years in Iran. METHOD: Iran pharmaceutical wholesale data were used to extract the annual consumption figures of the opioid analgesics in group N02A of the World Health Organization (WHO) Anatomical Therapeutic Chemical classification and were available in Iran (morphine, fentanyl, pethidine, and oxycodone as strong opioids and, tramadol and pentazocine as weak opioids), from 2000 to 2018. Using Defined Daily Dose (DDD) by WHO and Oral Morphine Equivalent (OMEQ), the amount of annual consumption was determined in DDD/1000 inhabitants/Day (DID) and OMEQ (mg)/1000 inhabitants/Day (OID). RESULTS: Total opioid analgesic utilization based on DID and OID increased 31.12-fold (from 0.0196 to 0.61) and 21.06-fold (from 1.97 to 41.5 mg) over 19 years, respectively with a significant sharp increase from 2003 to 2006 (ß = 1.78 (DID), P value < 0.001). Medications that constituted 70% of annual opioid analgesics utilization were morphine in 2000, compared to tramadol in 2018. The annual weak and strong opioids share were 86.7% and 13.2% in 2018, respectively. CONCLUSION: Despite considerable growth in the consumption of opioid analgesics in Iran over nearly two decades, the consumption amount remained low, which might signal sub-optimal pain management. On the other hand, misuse and abuse seem to be the main reason behind significant increases in the consumption of opioid analgesics with less controlled distribution.

Adverse drug reactions of Rituximab in patients suffering from autoimmune neurological diseases.

BACKGROUND: Rituximab, a chimeric human/mouse monoclonal antibody targeting CD-20 antigens, has been used recently for various rheumatological and autoimmune diseases, including autoimmune neurological disorders. OBJECTIVES: We aimed to study the frequency, seriousness, causality, and preventability of adverse drug reactions (ADRs) of rituximab in Iranian patients with autoimmune neurological diseases. METHODS: In this cross-sectional observational study, patients with autoimmune neurological diseases who had an indication for rituximab treatment were enrolled. Naranjo adverse drug reaction probability scale was used to assess the causality of ADRs, and the preventability of the ADRs was determined by P-Method. The seriousness of ADRs was also determined. RESULTS: A total of 264 ADRs were recorded from 97 patients. The Median (min-max) number of ADRs experienced by patients was 3 (1-7) events. 11.3% of patients experienced serious ADRs. 18.2% and 26.9% of ADRs were Definite and Probable, respectively. Only 5% of the ADRs were ''preventable". The most frequent ADRs were rituximab infusion-related reactions. CONCLUSION: Rituximab had an acceptable safety profile in our study patients. However, there must be certain cautions regarding the use of the medication for the elderly or patients with a compromised immune system. Timely detection and management of ADRs would also be crucial to prevent severe and permanent damages. Moreover, considering that rituximab is used as an off-label treatment for autoimmune neurological diseases, a risk-benefit assessment would be necessary before deciding on the treatment choice.

Prescribing Pattern and Prescription-writing Quality of Antineoplastic Agents in the Capital City of a Middle-income Developing Country.

OBJECTIVE: Cancer is a global health concern with growing incidence worldwide. Chemotherapy is the main treatment modality in many malignancies. This study aimed at evaluation of antineoplastic prescribing pattern and prescription-writing quality in the capital city of Iran. METHODS: All dispensed chemotherapy prescriptions by four main authorized pharmacies in Tehran during 1 month were targeted. Prescriptions with no antineoplastic medications or written by specialties other than oncology-related fields were excluded from the study. From the total 10,944 eligible prescriptions, 2736 (25%) prescriptions were selected randomly for data extraction. FINDINGS: Total 5784 antineoplastic medications were written by 239 physicians; most of them were adult hematologist-oncologist (69.0%) and male (86.6%). Each prescription contained an average of 1.8 (±0.9) antineoplastic medications. The most widely prescribed antineoplastic agents were cyclophosphamide (16.2%), fluorouracil (15.2%), doxorubicin (12.8%), and oxaliplatin (11.0%). The quality of prescription writing was poor; diagnosis, drug dosing, treatment schedule, and instructions were mostly absent. Sixty percent of drugs were written in brand names. CONCLUSION: The prescribing writing quality was poor and patients were at great risk of medication errors. Prompt action including policies and educational strategies should be taken to assure effective and safe patient treatment with antineoplastic medications.

Adherence to medications, self-care activity, and HbA1c status among patients with type 2 diabetes living in an urban area of Iran.

BACKGROUND: Appropriate pharmacotherapy, self-care and adherence to medications are crucial to diabetes control. We aimed to study the diabetes care and glycemic control in patients with type two diabetes living in an urban area of Iran. METHODS: In this cross-sectional study, patients with type 2 diabetes who attended a referral university affiliated community pharmacy and an accredited pathobiology laboratory in the 17th district of Tehran were evaluated. Data including demographics, medical and drug history were collected. Self-care activity (Diabetes Self-care Activity Measurement Scale) and medication adherence (8-item Morisky Medication Adherence scale) were also assessed. After completing the questionnaires, the patients were referred to the laboratory for Hemoglobin A1c test. RESULTS: Three hundred forty-eight patients (60.3% females) were recruited. The mean (SD) of patients' age was 55.82 (12.72) and 75.3%of them were Illiterate or had primary education. Mean (SD) of Hemoglobin A1c levels was 8.39 (2.03) and 33% of patients had levels higher than 9%. Among study patients, 186 (53.4%) patients received monotherapy for diabetes type 2 and 200 (57.5%) patients had low adherence to medications. Physical activity, blood glucose self-monitoring and foot care were domains of self-care with the fewest practice. Re-using a pen or syringe needle more than once was reported by 83% of patients and mean (SD) time of re-using a pen needle was 9.11 (8.74). CONCLUSION: Poor glycemic control, low medication adherence, inadequate self-care activities, signals of inappropriate pharmacotherapy and inadequate medical visits and monitoring in the study patients highlight the importance of providing accessible and affordable health care services in the region. Moreover, educational needs of the patients should be considered especially in an area in which the majority of patients are old and illiterate and have low socioeconomic status.

Vancomycin-Induced Thrombocytopenia: A Narrative Review.

Thrombocytopenia has been reported as an adverse reaction of numerous drugs. Vancomycin is often overlooked as a culprit but has been associated with several cases of thrombocytopenia that were not well described in the literature. A literature search was conducted to find reports of thrombocytopenia induced by vancomycin. Biomedical databases including 'PubMed', 'Scopus', and 'Web of Science' were searched using terms 'vancomycin', 'platelet', 'pancytopenia', 'thrombocytopenia', and 'bleeding'. English language articles published before July 2015 were included. Thirty-nine papers including 29 case reports (30 cases), five observational studies, two clinical trials, two letters, and one case series remained for final analysis. The main route of administration was intravenous infusion. This adverse reaction seems to be duration dependent with the mean time to platelet nadir count of 8 days in reported cases. The interval may be significantly shorter in re-exposure to the drug. Platelet nadir counts ranged from 2000 to 100,000/mL in patients who experienced bleeding. Vancomycin-specific antibodies were detected in 13 of 17 patients who were tested in the case reports. Based on the Naranjo Adverse Drug Reaction Probability Scale, reaction was 'definite', 'probable', and 'possible' in 1, 15, and 14 patients, respectively. Among 30 cases, vancomycin was discontinued in 29 patients and platelets returned to normal counts within 5-6 days in 17 of them; in one patient, vancomycin was not discontinued, but platelet count recovered 11 days after the nadir time. Transfusion might be recommended if severe thrombocytopenia and bleeding occurs. Intravenous immunoglobulins, corticosteroids, rituximab, and plasma exchange should be reserved for patients with resistant thrombocytopenia and severe bleeding as mentioned in a number of reports.

Predictive performance of Vancomycin population pharmacokinetic models in Iranian patients underwent hematopoietic stem cell transplantation.

OBJECTIVE: Many hematopoietic stem cell transplantation (HSCT) patients receive vancomycin empirically during febrile neutropenia. There are several models for estimation of vancomycin pharmacokinetic parameters and calculation of initial dosing regimen accordingly. However, the performance of these methods in HSCT patients remained to be evaluated. The aim of the study was to determine which of the vancomycin population pharmacokinetic methods best fit Iranian HSCT patients. METHODS: In order to evaluate predicted performance of seven vancomycin population pharmacokinetic models, the pharmacokinetic parameters of patients were estimated using each model's equations. Then the predicted steady-state trough vancomycin concentration was calculated based on each model's parameters and using a formula based on Sawchuk-Zaske method. The predicted steady-state trough vancomycin concentration and the real measured concentrations were compared to see which method was the most precise and least biased using mean squared error (MSE) and mean prediction error (ME) respectively. FINDINGS: Forty-six patients (65% men) were included in the study. Calculated metrics showed a range of 38% under-prediction bias with Rodvold to 34% over-prediction bias with Matzke and Burton models. Birt and revised Burton methods showed no significant bias (ME [95% confidence interval (CI)]: -0.067 [-0.235-0.101] and 0.066 [-0.105-0.238]). Birt and revised Burton were not different significantly considering MSE (95% CI) of 0.385 (0.227-0.544) and 0.401 (0.255-0.546), respectively. Comparisons of precision with naive predictors revealed a delta MSE (95% CI) of -0.128 (-1.379-1.890) for Birt and 0.026 (-0.596-0.940) for revised Burton models. CONCLUSION: Although the Birt and Burton revised methods performed well, none of the studied models showed acceptable performance to be implemented as a routine method for initial dose calculation in HSCT patients. A vancomycin pharmacokinetic model specific for this high-risk subpopulation of Iranian patients should be designed and validated.

Urine neutrophil gelatinase associated lipocalin as an early marker of acute kidney injury in hematopoietic stem cell transplantation patients.

Acute kidney injury (AKI) is common in hematopoietic stem cell transplantation (HSCT) patients with an incidence of 21-73%. Prevention and early diagnosis reduces the frequency and severity of this complication. Predictive biomarkers are of major importance to timely diagnosis. Neutrophil gelatinase associated lipocalin (NGAL) is a widely investigated novel biomarker for early diagnosis of AKI. However, no study assessed NGAL for AKI diagnosis in HSCT patients. We performed further analyses on gathered data from our recent trial to evaluate the performance of urine NGAL (uNGAL) as an indicator of AKI in 72 allogeneic HSCT patients. AKI diagnosis and severity were assessed using Risk-Injury-Failure-Loss-End-stage renal disease and AKI Network criteria. We assessed uNGAL on days -6, -3, +3, +9 and +15. Time-dependent Cox regression analysis revealed a statistically significant relationship between uNGAL and AKI occurrence. (HR = 1.04 (1.008-1.07), p = 0.01). There was a relation between uNGAL day + 9 to baseline ratio and incidence of AKI (unadjusted HR = 1.047 (1.012-1.083), p < 0.01). The area under the receiver-operating characteristic curve for day + 9 to baseline ratio was 0.86 (0.74-0.99, p < 0.01) and a cut-off value of 2.62 was 85% sensitive and 83% specific in predicting AKI. Our results indicated that increase in uNGAL augmented the risk of AKI and the changes of day +9 uNGAL concentrations from baseline could be of value for predicting AKI in HSCT patients. Additionally uNGAL changes preceded serum Cr raises by nearly 2 days.

A double-blind, randomized, controlled trial on N-acetylcysteine for the prevention of acute kidney injury in patients undergoing allogeneic hematopoietic stem cell transplantation.

Acute kidney injury (AKI) is one of the complications of hematopoietic stem cell transplantation and is associated with increased mortality. N-acetylcysteine (NAC) is a thiol compound with antioxidant and vasodilatory properties that has been investigated for the prevention of AKI in several clinical settings. In the present study, we evaluated the effects of intravenous NAC on the prevention of AKI in allogeneic hematopoietic stem cell transplantation patients. A double-blind randomized placebo-controlled trial was conducted, and 80 patients were recruited to receive 100 mg/kg/day NAC or placebo as intermittent intravenous infusion from day -6 to day +15. AKI was determined on the basis of the Risk-Injury-Failure-Loss-End-stage renal disease and AKI Network criteria as the primary outcome. We assessed urine neutrophil gelatinase-associated lipocalin (uNGAL) on days -6, -3, +3, +9 and +15 as the secondary outcome. Moreover, transplant-related outcomes and NAC adverse reactions were evaluated during the study period. Statistical analysis was performed using appropriate parametric and non-parametric methods including Kaplan-Meier for AKI and generalized estimating equation for uNGAL. At the end of the trial, data from 72 patients were analysed (NAC: 33 patients and placebo: 39 patients). Participants of each group were not different considering baseline characteristics. AKI was observed in 18% of NAC recipients and 15% of placebo group patients, and the occurrence pattern was not significantly different (p = 0.73). Moreover, no significant difference was observed between groups for uNGAL measures (p = 0.10). Transplant-related outcomes were similar for both groups, and all patients had successful engraftment. Three patients did not tolerate NAC because of abdominal pain, shortness of breath and rash with pruritus and were dropped from the intervention group before transplantation. However, the frequency of adverse reactions was not significantly different between groups. In conclusion, our findings could not show any clinical benefits from high-dose NAC particularly for AKI prevention in allogeneic hematopoietic stem cell transplantation patients.