Frequency and predictors of potential drug: Drug interactions in hospitalized patients with Parkinson's diseases

Introduction: Patients with Parkinson's disease are exposed to higher number of drugs on average than other elderly persons. Levodopa, of the mainstay of Parkinson's disease therapy, is frequently interacting with numerous drugs. Aim: The aim of this study was to identify predictors of potential drug-drug interactions (pDDIs) in hospitalized patients suffering from Parkinson's disease (PD). Material and Methods: This was a academic retrospective cross-sectional study in PD patients hospitalized at the Clinic of Neurology, Clinical Center Kragujevac. Medical records of hospitalized patients during the period 1.1.2017 - 31.12.2019 were analysed. The pDDIs were identified by means of Micromedex andLexi-Interact online softwares, and multivariate regression methods were used to reveal potential predictors of number of pDDIs per patient. Results: Micromedex detected 160 different pDDIs in 77.8% of 72 patients with PD. The most frequent pDDIs were those that involved aspirin (with bisoprolol, sertraline and perindopril). Predictors of pDDIs in general was total number of drugs, while use of antidepressants presented a significant risk factor for major pDDIs. Lexi-Interact revealed 310 pDDIs in 98.6% of patients. The three most common pDDIs were with levodopa (bisoprolol, clonazepam, perindopril). Total number of drugs, number of co-morbidities, hospitalization at the neurodegenerative ward, and use of antipsychotics were identified as the relevant predictors of pDDIs. Lexi-interact software detected significantly more pDDIs than Micromedex (p<0.001). Conclusion: Neurologists should pay special attention when deciding whether to administer new drug to a PD patient with multiple comorbidities, hospitalized in a neurodegenerative ward and/or taking antidepressant or antipsychotic drugs.

Hypocalcemia of the newborn due to red blood cell transfusion: Case report

Introduction: Hypocalcemia in preterm infants could occurs as early or late. Causes of late onset of hypocalcaemia: maternal vitamin D deficiency, metabolic syndromes, congenital abnormalities, iatrogenic (transfusion, bicarbonate therapy, phototherapy, antibiotics). Case report: The authors describe the occurrence of late hypocalcemia following transfusion of erythrocytes to the second newborn from a twin pregnancy born prematurely in the 32/33 week of gestation. Mother is diabetic and has hypertension, edema, hypothyroidism, and preeclampsia during pregnancy. Due to the detected pyelectasis in newborn, prophylactic use of cephalexin was introduced. At the end of the first month of life, anemia appear indicating a transfusion. The infant received 50 ml an O+ leukodepleted RBC transfusion. Immediately after transfusion was completed, there is a short-term deterioration of the general condition. Cyanosis, stiffness, trismus, and bradycardia appear within a few seconds. DAT was negative, bilirubin in the reference range. After transfusion, laboratory, echosonographic examination, neurological examination, EEG and ECG showed normal results. It was concluded that the adverse reaction was probably caused by transfusion. Conclusion: In preterm infants, hypocalcaemia may occur during transfusion due to citrate overload. Children of diabetic mothers, on antibiotic and photo therapy are at higher risk of developing hypocalcemia. Future studies should evaluate incidence rate of adverse transfusion reactions in newborns.

Easy to manage when recognized: Case report of Cutaneous Larva Migranss

Introduction: Cutaneous larva migrans (CLM) is a syndrome, defined by clinical appearance of slowly migrating cutaneous eruption caused by inoculation with animal hookworms larvae in the skin. Despite the typical clinical presentation, CLM is frequently misdiagnosed due to its rarity in temperate climate urban communities. Case Report: We report a case of a 42-year old female, admitted to an outpatient clinic with eruption of multiple intense pruritic, erythematous, exudative papules and oval plaques, located predominately on the back. The patient claimed that skin lesions started three weeks before the examination, during her vacation in Thailand, and at first, was taught to be caused by a contact with jelly fish. Lesions were treated unsuccessfully with oral antihistamines and various topical corticosteroids, which lead to more questions regarding the differential diagnosis. Dermoscopical and histopathological findings were indicative of parasitic infection, most likely CLM. A three-day course of oral albendazole, 400 mg daily, resulted in complete cure of the disease. Conclusions: Careful clinical examination and detailed history taken from the patient are fundamentals for creating a set of differential diagnoses, that can be further clarified by the use of laboratory findings, imaging methods (including dermoscopy) and biopsy with histopathology. Although CLM has a benign self-limiting course, intense itch may substantially impact the quality of life, and possible visceral involvement or concomitant parasitic infection may lead to serious health deterioration in unrecognized cases.

The case of nutcracker phenomenon associated with IgA nephropathy

Introduction: The nutcracker syndrome is a rare clinical entity caused by compression of the left renal vein by the superior mesenteric artery. Epidemiologically opposite, IgA nephropathy is the most common cause of idiopathic glomerulonephritis. A combination of the two diseases has previously been reported in a few cases. Case Report: Herein we report a case of a 22-year-old male patient admitted because of macroscopic hematuria due to excessive oral anticoagulation. He had prior evidence of proteinuria, microhematuria, impaired kidney function, and enlarged left kidney. He presented with fatigue, abdominal pain, nausea, and several instances of vomiting after a meal. A diagnosis of left renal vein compression and IgA nephropathy was made based on clinical, laboratory, radiological findings and kidney biopsy. The vascular anomaly was treated conservatively, while steroids were given to treat glomerulonephritis. The result was complete regression of symptoms, normal laboratory findings, and a significant drop in proteinuria. Conclusion: It is important to evaluate whether patients have nutcracker phenomenon before initiating treatment for IgA nephropathy and vice versa, as hematuria and proteinuria can be overlapping symptoms of both conditions. Renal biopsy should not be hesitated for differential diagnosis, and treatment should be highly individualized.

Self-medication for dysmenorrhea among Serbian medical students

Introduction: Primary dysmenorrhea is a common disorder in women, with a significant impact on quality of life. Aim: The objective of this academic study was to investigate the severity of dysmenorrhea in female students of the Faculty of Medicine in Novi Sad, to estimate the self-medication prevalence of primary dysmenorrhea, to identify the most commonly used conventional, herbal, homeopathic remedies and manner of their usage, as well as non-pharmacological measures in the treatment of primary dysmenorrhea. Material and Methods: This study was performed on a random sample of 100 respondents from different departments of the Faculty of Medicine in Novi Sad, from December 1st to December 15th, 2016. The data were obtained by using a standardized questionnaire. Results: The sample included 59 female medical students and 41 female students of the other study groups. Most of the respondents had medium expressed symptoms due to dysmenorrhea (48.0%). The most common symptoms were cramps and pain in the lower abdomen, anxiety, and appetite changes. 11% of respondents were absent from classes at the university minimum one day of each menstrual cycle, because of dysmenorrhea. 66% of respondents used drugs due to symptoms of dysmenorrhea. The most commonly used group of drugs were non-steroid anti-inflammatory drugs (75.76%), primarily ibuprofen (53.03%), and diclofenac (10.61%). Self-medication prevalence was 48.48%. Conclusion: According to the results of this study, dysmenorrhea symptoms significantly impact the quality of life.

DRESS syndrome without eosinophilia induced by Carbamazepine: A case report

Introduction: Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) is a rare, severe, systemic, drug-induced hypersensitivity syndrome, the most frequently associated with anticonvulsants. Case Report: A 35-years-old woman with a history of depression and hypothyroidism developed fever 39.5°C, enlarged, painful neck and axillary lymph nodes, slight facial edema around the mouth, confluent maculopapular rash, and laboratory signs of hepatocellular injury, leukocytosis and lymphopenia, but with normal eosinophil count. The syndrome was evident two weeks after starting carbamazepine, and gradually decreased after withdrawal of this drug and introduction of corticosteroid therapy. Conclusion: If a patient is taking carbamazepine and develops skin rash as well as fever and swollen lymph nodes, the physician should always check for internal organ damage and possible DRESS syndrome.

Benzodiazepines consumptions: Influence on traffic accidents

Introduction: Benzodiazepines belong to the group of anxiolytic sedatives and the most prescribed drugs in the world. Since these drugs have a potential for rapid anxiolytic effect and sedation, as well as driver capability impairment, there is a lack data of safety of benzodiazepines in traffic accidents. The aim: To make an assessment of the interconnection of time series of traffic accidents outcomes with time series of Benzodiazepine anxiolytic consumption in the Republic of Serbia. Methods: This paper is a part of IV phase academic study regarding the factors potentially affecting Benzodiazepine consumption and effects. We conducted a pharmaco-epidemiological time series analysis study of monthly sold Benzodiazepine anxiolytics in pharmacies and indicators of the crush road outcome on a monthly basis in the Republic of Serbia. The research was performed from January 2014 to December 2018. Results: Applying ARIMAX modeling we found a significantly link between DID of alprazolam with monthly total traffic accident, a high stochastic regression positive association of DID of Diazepam with the dependent variable monthly total traffic accident, the prediction of monthly fatalities of traffic accident or traffic accident with severe or slight injuries per total traffic accident we have demonstrated positive influence of DID of alprazolam in second-order autoregressive and moving average model with constant. In prediction of monthly fatalities traffic accident, a significant positive influence of DID of benzodiazepines (all together) in auto-regression model without constant was demonstrated. Conclusion: Consumption of both long-acting (over 12 h) and short-acting benzodiazepines together with all other causes highly determined the total number of traffic accidents on a monthly basis in 2014-2018 in the Republic of Serbia. An assessment of the interconnection of time series of traffic accidents outcomes with time series of Benzodiazepine anxiolytic consumption in the Republic of Serbia we found a significant positive influence of DID of benzodiazepines on traffic accidents outcomes. In total, all used benzodiazepines increase the number of fatal traffic accidents by 8.5 fold per month. Alprazolam additionally contributed with about ten percent (9.7%) to the frequency of traffic accidents on a monthly basis. Measures to prevent traffic accidents at all levels should be effective immediately in order to achieve positive results timely. The authors suggest that the great responsibility is raising awareness of compliance with traffic regulations with doctors who prescribe benzodiazepines.

Sunshine hours and utilization of benzodiazepines

Introduction: Benzodiazepines belong to the group of anxiolytic sedatives and the most prescribed drugs in the world. The authors conducted this pilot study based n large number of patients reports that they were less anxious and felt better overall by migrating to sunnier environments. Aim: We estimated the impact of the total sunshine hours per month on daily exposure of the population to Benzodiazepine anxiolytic on a monthly basis in the Republic of Serbia. Material and Methods: We conducted a retrospective academic IV phase study, which tested the correlation of time series of monthly sold Benzodiazepine anxiolytics in pharmacies and total sunshine hours per month in the Republic of Serbia, from January 2014 to May 2019. Results: According to the seasons, we did not find any difference in the increase of the population exposure to benzodiazepines. A difference was found between bromazepam consumption compared to cumulative monthly. Bromazepam consumption was negatively correlated with the cumulative monthly sunshine hours. The cutoff value for bromazepam was 131.45 cumulative monthly sunshine hours. Conclusion: This is the first pharmaco-epidemiologic study to prove that the population's exposure to benzodiazepines, in addition to the implicit health and economic effects on physicians' prescribing habits for these drugs, can be independently linked to the cumulative effects of monthly sunshine hours on the population. No difference in Benzodiazepine consumption was found in relation to the seasons (spring/summer vs autumn/winter). In months where sunshine hours was ≥135.45, the need for bromazepam was significantly reduced. Seasonal variation of climatic effects of total monthly sunshine hours is significantly correlated with the population's need for benzodiazepines with anxiolytic effects longer than 12 hours.

Excipients of inhaled medications with potential to cause adverse reactions

Introduction: In addition to the active pharmaceutical ingredient (API), the composition of the medicines also includes excipients which are only ideally completely pharmacologically inactive. It has been shown that excipients in inhaled preparations can cause effects opposite to the pharmacological effect of the medicine. Aim: The Aim of the study was to identify potentially harmful excipients in inhaled medicines approved in the Republic of Serbia. Material and Methods: The academic study was conducted during April 2021 and included the analysis of medicines that received a marketing authorization from the Medicines and Medical Devices Agency of Serbia (ALIMS). Qualitative compositions of inhaled medicines available in Summaries of product characteristics (SmPC) on the ALIMS's official website were observed. Excipients considered potentially harmful if they are recognised as excipients with known effect (EKE) in Serbian and European regulations. Results: Total of 46 inhalation preparations that are approved in Serbia were analyzed. In their composition were found 17 different excipients. By comparing appropriate domestic and European regulations three excipients from examined preparations that represent potential causative agents of adverse drug reactions (ADRs) were identified: lactose-monohydrate, ethanol and benzalkonium chloride. It has been shown that disodium EDTA is also a potential causative agent of ADRs, but it is not classified as EKE. Conclusion: Neither domestic nor international regulations have classified EDTA and its salts as EKE and they should be given special attention in the future as potential causative agents of ADRs. It has been shown that benzalkonium chloride is the only excipient that can lead to bronchospasm and it was found in two inhaled medicines.

Focus group and Delphi process: Stroke and potential drug-drug Interactions (pDDI) in the neurological Intensive Care Unit (NICU)

Introduction: The clinical significance of potential drug-drug interactions (pDDIs), especially in the intensive care unit (ICU) manifested mostly as adverse drug reactions. Aim: The goal of this research was to conduct a focus group, in which the participants were decisionmakers in acute ischemic stroke patient treatment. Also, the aim was to reach a consensus, due to the Delphi process, between neurologists and clinical pharmacologists regarding this highly vulnerable group of patients. Material and Methods: In this academic research, so-called applied focus group (the goal was to reach practical decisions) and clinical focus group (determining motives, predeterminations, bias, prejudice and analyzing the behavior leading to a certain outcome) was done. Results: Continuing medical education of neurologists is needed regarding pDDIs and the use of an online pDDIs checker. Certain groups of patients with AIS are at particular risk of exposure to pDDIs. Certain drug groups are more likely to interact with other drugs. Conclusions: Defining medical recommendations/guidelines on evidence base medicine about pDDIs in patients with AIS would significantly contribute to reducing their frequency in this vulnerable patient population.