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Background and Objectives: Aneurysmal subarachnoid hemorrhage (ASAH) is defined as bleeding in the subarachnoid space caused by the rupture of a cerebral aneurysm. About 11% of people who develop ASAH die before receiving medical treatment, and 40% of patients die within four weeks of being admitted to hospital. There are limited data on single-center experiences analyzing intrahospital mortality in ASAH patients treated with an endovascular approach. Given that, we wanted to share our experience and explore the risk factors that influence intrahospital mortality in patients with ruptured intracranial aneurysms treated with endovascular coil embolization. Materials and Methods: Our study was designed as a clinical, observational, retrospective cross-sectional study. It was performed at the Department for Radiology, University Clinical Center Kragujevac in Kragujevac, Serbia. The study inclusion criteria were ≥18 years, admitted within 24 h of symptoms onset, acute SAH diagnosed on CT, aneurysm on DSA, and treated by endovascular coil embolization from January 2014 to December 2018 at our institution. Results: A total of 66 patients were included in the study-48 (72.7%) women and 18 (27.3%) men, and 19.7% of the patients died during hospitalization. After adjustment, the following factors were associated with in-hospital mortality: a delayed ischemic neurological deficit, the presence of blood in the fourth cerebral ventricle, and an elevated urea value after endovascular intervention, increasing the chances of mortality by 16.3, 12, and 12.6 times. Conclusions: Delayed cerebral ischemia and intraventricular hemorrhage on initial head CT scan are strong predictors of intrahospital mortality in ASAH patients. Also, it is important to monitor kidney function and urea levels in ASAH patients, considering that elevated urea values after endovascular aneurysm embolization have been shown to be a significant risk factor for intrahospital mortality.
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Embolización Terapéutica , Mortalidad Hospitalaria , Hemorragia Subaracnoidea , Humanos , Femenino , Masculino , Hemorragia Subaracnoidea/mortalidad , Hemorragia Subaracnoidea/terapia , Hemorragia Subaracnoidea/complicaciones , Persona de Mediana Edad , Embolización Terapéutica/métodos , Embolización Terapéutica/estadística & datos numéricos , Estudios Retrospectivos , Estudios Transversales , Anciano , Factores de Riesgo , Adulto , Procedimientos Endovasculares/métodos , Serbia/epidemiología , Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/mortalidad , Aneurisma Intracraneal/terapia , Aneurisma Roto/complicaciones , Aneurisma Roto/mortalidad , Aneurisma Roto/terapiaRESUMEN
Objective: The pharmacokinetics of meropenem are significantly altered in critically ill patients. A population pharmacokinetic study was designed to estimate typical values of meropenem clearance in critically ill patients and evaluate potential factors of influence. Methods: After meropenem reached a steady state in each patient, two blood samples were taken within the dose interval. The one-compartment pharmacokinetic model based on the data from 101 intensive care unit patients was built using NONMEM software. Results: Typical values of meropenem clearance and volume of distribution were 3.80 L/h and 3.52 L, respectively. In the final model, meropenem clearance was influenced by serum concentrations of creatinine (CRE), leukocyte count (WBC), hypertension (HTA), and concomitant use of vancomycin (VAN) or colistimethate (COL): CL (L/h) = 5.29 × CRE ^ 0.000001 × WBCs ^ (-0.165) + 0.000001 × HTA + 0.825 × VAN + 1.28 × COL. Conclusion: In order to achieve effective plasma concentrations of meropenem in critically ill patients, the meropenem dosing regimen should be adjusted according to individual values of drug clearance.
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INTRODUCTION: This study aimed to compare the prevalence of potentially inappropriately prescribed drugs in hemodialysis patients and patients with chronic kidney disease who did not require renal replacement therapy, as well as to identify risk factors associated with potentially inappropriate prescribing. METHODS: The study was designed as a cross-sectional study conducted at the Department of Nephrology, Clinical Center in Nis, Serbia. The patients were divided into two groups: (1) patients on hemodialysis treatment and (2) patients with various degrees of chronic kidney disease without renal replacement therapy. The presence or absence of potentially inappropriate prescribing was determined using the 2015 AGS Beers criteria. FINDINGS: The study included a total of 218 patients aged 65 years and over. The number of patients with potentially inappropriate prescribed drugs did not differ significantly (chi-square = 0.000, p = 1.000) between patients on hemodialysis (27 of 83, i.e., 32.5%) and patients with various degrees of chronic kidney disease without renal replacement therapy (44 of 135, i.e., 32.6%). Factors associated with potentially inappropriate prescribing in hemodialysis patients were the number of drugs (hazard ratio [HR] = 1.919, 95% confidence interval [CI]: 1.325-2.780) and number of comorbidities (HR = 1.743, 95% CI: 1.109-2.740). The number of drugs (HR = 1.438, 95% CI: 1.191-1.736) was the only independent factor associated with increased risk of potentially inappropriate prescribing in patients without renal replacement therapy. DISCUSSION: Our study showed that potentially inappropriate prescribing is a relatively frequent phenomenon present in about a third of patients in both study groups. The number of prescribed drugs was the main factor associated with the increased risk of potentially inappropriate prescribing in both groups.
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BACKGROUND: Carbamazepine is one of the most commonly used antiseizure medications. Although carbamazepine pharmacokinetics in epileptic patients is well described, much less is known about these processes in the patients who experienced self-poisoning episode by this drug. Therefore, the aim of our investigation was to perform population toxicokinetics of carbamazepine and its metabolite carbamazepine-10,11-epoxide in adults. RESEARCH DESIGN AND METHODS: Software program NONMEM and the ADVAN2 TRANS2 subroutine were used for establishing a population toxicokinetic model for the estimation of clearance and volume of distribution based on of the sum values of carbamazepine and carbamazepine-10,11-epoxide concentrations. RESULTS: Our results indicated that the adult patients' ability to eliminate carbamazepine and carbamazepine-10,11-epoxide following acute carbamazepine self-poisoning was strongly associated with the high levels of CRP and ASP, as well as by the treatment with sedation. CONCLUSIONS: Our study should provide better understanding of the toxicokinetics of carbamazepine taken in overdose and better management of patient population admitted to hospital.
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PURPOSE: The study aimed to determine the typical clearance and volume of distribution values of tamsulosin in patients with benign prostatic hyperplasia (BPH), and to identify factors with a measurable impact on the drug's elimination. METHODS: This open-label, single-arm population pharmacokinetic study involved 65 adult men with BPH who had been on tamsulosin therapy for at least seven days. The steady-state serum concentrations of tamsulosin were measured using liquid chromatography-tandem quadrupole mass spectrometry. Population pharmacokinetic parameters, their variability, and influencing factors were estimated based on a two-compartment pharmacokinetic model using NONMEM software. RESULTS: The estimated tamsulosin clearance in BPH patients was 0.719 L/h, and the steady-state volume of distribution was 32 L. Neither renal nor liver function parameters had a statistically significant effect on tamsulosin clearance. However, a positive correlation was observed between hemoglobin levels and tamsulosin clearance in the BPH patient cohort. CONCLUSION: Our investigation reveals significant associations between tamsulosin pharmacokinetics and specific characteristics of patients with lower urinary tract symptoms (LUTS) due to BPH. The study highlights that tamsulosin clearance is associated with hemoglobin levels in patients with LUTS/BPH. This study underscores the importance of considering patient-specific factors when managing BPH treatment with tamsulosin, emphasizing associations rather than causative relationships.
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Hiperplasia Prostática , Tamsulosina , Humanos , Hiperplasia Prostática/tratamiento farmacológico , Masculino , Tamsulosina/farmacocinética , Tamsulosina/uso terapéutico , Anciano , Persona de Mediana Edad , Antagonistas de Receptores Adrenérgicos alfa 1/farmacocinética , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Anciano de 80 o más Años , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Síntomas del Sistema Urinario Inferior/etiologíaRESUMEN
Objective: Our aim was to compare the costs and efficacy of ambroxol in combination with imiglucerase with the costs and efficacy of imiglucerase only in the treatment of Gaucher disease type 2 (GD2) in the socio-economic settings of the Republic of Serbia, an upper-middle-income European economy. Methods: The perspective of the Serbian Republic Health Insurance Fund was chosen for this study, and the time horizon was 6 years. The main outcomes of the study were quality-adjusted life years gained with ambroxol + imiglucerase and comparator, and direct costs of treatment. The study was conducted through the generation and simulation of the Markov chain model. The model results were obtained after Monte Carlo microsimulation of a sample with 1,000 virtual patients. Results: Treatment with ambroxol in combination with imiglucerase was cost-effective when compared with imiglucerase only and was associated with positive values of net monetary benefit regardless of the onset of the disease. Such beneficial result for ambroxol and imiglucerase combination is primarily driven by the low cost of ambroxol and its considerable clinical effectiveness in slowing the progression of neural complications of GD2. Conclusion: If ambroxol and imiglucerase are used in combination for the treatment of GD2, it is more cost-effective than using imiglucerase alone.
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Schizophrenia is a chronic mental illness with a poor quality of life (QoL). The main aim of this study was to measure the QoL and factors that affect the QoL of patients with schizophrenia placed in a social welfare institution. This cross-sectional study included 287 patients with schizophrenia who were treated in a long-stay social care institution in which QoL was assessed using five different instruments: the World Health Organization Quality of Life scale, the EuroQoL Five-Dimension-Five-Level scale (including the visual analog scale), the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form, and the Brief Psychiatric Rating Scale. To determine the impact of patients' characteristics on score values, multiple linear regression using backward elimination was employed. Due to non-normality in the distribution of the dependent variables, a Box-Cox power transformation was applied to each dependent variable prior to conducting multiple linear regression analysis. Results revealed that patients with schizophrenia have lower QoL. Our study revealed that age, level of education, type of accommodation, type of pavilion, age of onset of the disease, number of prescribed antipsychotics, number of psychiatric comorbidities, duration of therapy, and the number of daily doses of antipsychotics are dominant contributors to the QoL in patients with schizophrenia who were treated in social welfare institution.
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Serious hematological adverse drug reactions (HADRs) may lead to or prolong hospitalization and even cause death. The aim of this study was to determine the regulatory factors associated with HADRs caused by drugs that were authorized up to July 2023 by the European Medicines Agency (EMA) and to evaluate the frequency of HADRs. Using a cross-sectional approach, the type and frequency of HADRs were collected from the Summaries of Product Characteristics of Drugs Authorized by the EMA and analyzed within proprietary, nonproprietary, and biosimilar/biological frameworks. Multivariate statistical analysis was used to investigate the associations of generic status, biosimilar status, conditional approval, exceptional circumstances, accelerated assessment, orphan drug status, years on the market, administration route, and inclusion on the Essential Medicines List (EML) with HADRs. In total, 54.78% of proprietary drugs were associated with HADRs at any frequency, while anemia, leucopenia, and thrombocytopenia were observed in approximately 36% of the patients. The predictors of any HADR, anemia, and thrombocytopenia of any frequency are generic status, biosimilar status, and inclusion on the EML, while the only protective factor is the administration route. Biosimilars and their originator biologicals have similar frequencies of HADRs; the only exception is somatropin. Knowledge of the regulatory factors associated with HADRs could help clinicians address monitoring issues when new drugs are introduced for the treatment of patients.
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Anemia , Biosimilares Farmacéuticos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Medicamentos Esenciales , Leucopenia , Trombocitopenia , Humanos , Preparaciones Farmacéuticas , Biosimilares Farmacéuticos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Medicamentos Genéricos , Trombocitopenia/inducido químicamente , Leucopenia/inducido químicamente , Anemia/inducido químicamente , Anemia/tratamiento farmacológico , Aprobación de DrogasRESUMEN
OBJECTIVE: To analyze the level of fear and anxiety related to radiotherapy in oncology patients treated before and during the COVID-19 pandemic, as well as to examine whether the advancement of radiotherapy centers leads to any reduction in the patient's fear in emergency situations. METHODS: Two cross-sectional studies were conducted in two time frames (2016 and 2022) based on the analysis of the intensity of anxiety and fear of radiotherapy in oncology patients with assistance. A questionnaire for assessing fear of radiotherapy in oncology patients and Zung's and Beck's self-reported anxiety scales were used. The first part of the research integrated all data of research interest obtained from patients treated with radiotherapy during 2016, and the second cross-sectional study included all patients treated in 2022 during the COVID-19 pandemic. The study was prepared according to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist. RESULTS: The first cross-sectional study had 154 participants who had been treated with radiotherapy, while in the second study, there were 159 patients. Patients treated in 2022 show significantly higher levels of fear and anxiety. External beam radiotherapy and brachytherapy simultaneously used in both studies increased the level of fear and anxiety. CONCLUSION: The conducted research showed exceptional differences in the intensity of fear and anxiety in patients treated with radiotherapy in different health situations, as was the case during the COVID-19 pandemic, with a significant impact on the stability of the health system and the challenges to providing standard services.
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INTRODUCTION: The prevalence of potential drug-drug interactions (pDDIs) is becoming a major safety concern, as it has been previously linked to a significant number of adverse drug events and could have serious consequences for patients, including death. This is especially relevant for patients with chronic renal failure, as they are particularly vulnerable to drug-drug interactions. The aim of this study was to evaluate the prevalence and associated factors of pDDIs in patients receiving chronic peritoneal dialysis. METHODS: An observational, cross-sectional study was conducted on consecutive peritoneal dialysis patients attending four tertiary care hospitals for regular monthly examination. The primary outcome was the number of pDDIs identified using Lexicomp. Potential predictors were determined using multiple linear regression. RESULTS: Total number of patients included in the study was 140. The results showed that pDDIs were highly prevalent, especially in patients who use antiarrhythmics (p = 0.001), have diabetes mellitus (p = 0.001), recently started peritoneal dialysis (p = 0.003), or have higher number of prescribed drugs (p < 0.001). Number of prescribed drugs (p < 0.001) remained a significant predictor of high-risk pDDIs in addition to the female gender (p = 0.043). CONCLUSION: Clinicians should be particularly cautious when prescribing multiple medications to high-risk patients, such as peritoneal dialysis patients, to mitigate the risk of drug-drug interactions and associated adverse health outcomes.
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Interacciones Farmacológicas , Diálisis Peritoneal , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Factores de Riesgo , Anciano , Adulto , Fallo Renal Crónico/terapia , Prevalencia , PolifarmaciaRESUMEN
Calcitonin gene-related peptide neurotransmission was the target for recent development of monoclonal antibodies that effectively prevent attacks of both episodic and chronic migraine. The aim of this narrative review was to offer deeper insight into drug-drug, drug-food and drug-disease interactions of monoclonal antibodies approved for prevention of migraine attacks. For this narrative review, relevant literature was searched for in MEDLINE and Google Scholar databases, covering the 1966-2023 and 2006-2023 periods, respectively. The ClinicalTrials.gov database was also searched for relevant clinical studies whose results had not been published previously in medical journals, covering 2000-2023. Monoclonal antibodies (erenumab, fremanezumab, galcanezumab and eptinezumab) augment prophylactic action of gepants and onabotulinumtoxin A and somewhat increase efficacy of triptans used to abort migraine attacks; however, their adverse reactions may also be augmented. Pharmacokinetic interactions and interactions in general with drugs used for other indications except migraine are negligible, as are drug-food interactions. However, monoclonal antibodies may worsen diseases with already weakened CGRP neurotransmission, Raynaud phenomenon and constipation. Monoclonal antibodies used for prevention of migraine do not engage in significant pharmacokinetic interactions with other drugs; however, they do engage in pharmacodynamic interactions with other anti-migraine drugs, additively augmenting their prophylactic action, but also increasing frequency and severity of adverse reactions, which are a consequence of the CGRP neurotransmission interruption.
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Anticuerpos Monoclonales , Péptido Relacionado con Gen de Calcitonina , Interacciones Farmacológicas , Trastornos Migrañosos , Trastornos Migrañosos/tratamiento farmacológico , Humanos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/efectos adversos , Péptido Relacionado con Gen de Calcitonina/inmunología , Péptido Relacionado con Gen de Calcitonina/antagonistas & inhibidores , Antagonistas del Receptor Peptídico Relacionado con el Gen de la Calcitonina/farmacología , Antagonistas del Receptor Peptídico Relacionado con el Gen de la Calcitonina/uso terapéutico , Interacciones Alimento-Droga , AnimalesRESUMEN
The calcitonin gene-related peptide transmission was the target for recent development of drugs that effectively prevent attacks of both episodic and chronic migraine. The aim of this narrative review was to offer deeper insight into pharmacokinetics of monoclonal antibodies approved for prevention of migraine attacks. For this narrative review, relevant literature was searched for in MEDLINE and Google Scholar databases, covering periods 1966-2023 and 2006-2023, respectively. The ClinicalTrials.gov database was also searched for relevant clinical studies whose results had not been published previously in medical journals, covering the period 2000-2023. The monoclonal antibodies from this group are distributed mainly in the plasma and part of the extracellular space; they are neither metabolized in the liver nor excreted via the kidneys. The elimination of galcanezumab, eptinezumab and fremanezumab takes place only by a non-specific linear process via the reticuloendothelial system in the liver, while erenumab is eliminated by a non-specific process and by a specific, saturable process because of binding to receptors located on the cell membrane. Since the elimination processes do not have a large capacity, the half-life is about 2 weeks for erenumab and about 4 weeks for other monoclonal antibodies. Variability in the pharmacokinetics of these monoclonal antibodies is small in different subpopulations, and body weight is the only parameter to consider when choosing the dose of these drugs.
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Anticuerpos Monoclonales , Péptido Relacionado con Gen de Calcitonina , Trastornos Migrañosos , Humanos , Trastornos Migrañosos/tratamiento farmacológico , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales/uso terapéutico , Péptido Relacionado con Gen de Calcitonina/inmunología , Anticuerpos Monoclonales Humanizados/farmacocinética , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antagonistas del Receptor Peptídico Relacionado con el Gen de la Calcitonina/farmacocinética , AnimalesRESUMEN
Background/purpose: Decubital lesions or traumatic ulcers caused by dentures usually appear one or two day(s) after new dentures placement due to mismatch of the microrelief of the tissue and the microrelief of the gingival surface of the prosthesis. The study aimed to analyze factors that could influence the healing of ulcers during a one-week period after the placement of new partial and complete dentures. Materials and methods: The prospective cohort study included 60 patients with new denture-induced traumatic ulcers. Traumatic ulcers were treated with denture adjustment, or combination of adjustment with 0.2% or 0.3% hyaluronic acid gels respectively for seven days. Healing of ulcers were observed through measurement of perimeter, area, maximum and minimum diameters on digital photographs. Multivariate logistic regression was used to predict other factors that could affect healing process. Results: Perimeter, area, maximum and minimum diameters of denture-related ulcers were significant decreased after application of gels on the fifth and seventh day. The fifth day ulcers were not healed if dentures were only adjusted, while healed lesion was 40% for the other two groups. On the seventh day, the percent of healed lesion in the group with dentures adjustment was 20%, while it was increased to 75% healed lesions for combination of denture adjustment and hyaluronic acid gels. Anticoagulant/anti-aggregation drugs also had positive impact on ulcer healing; antihypertensives that included diuretics slowed ulcer healing, other monitored factors in the study did not show a significant impact. Conclusion: Hyaluronic acid in combination with the dentures adjustment for seven days leads to higher healing rate, and reduction in size of ulcers that did not heal until this time point.
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PURPOSE: When carrying out prosthetic rehabilitation of edentulous and partially edentulous patients, great attention is paid to the personal attitude of the patients, their satisfaction with oral health and psychosocial interaction due to tooth loss, as well as the treatment of the resulting disorders. This attention has led to the development of various instruments for examining the quality of life related to oral health. The aim of this study was to develop and validate a reliable instrument in the Serbian language suitable for measuring oral health-related quality of life in patients who have been rehabilitated with complete or partial dentures. Ðaterials and Methods: The study was unicentric and cross-sectional, and assessed the reliability and validity of a newly developed instrument for measuring the oral health-related quality of life in denture wearers (OHRQoL-DW). It was conducted on a sample of 200 adults from Serbia, wearers of various types of dentures, with a mean age 66.9 ± 10.3 years and male/female ratio of 86/114 (43%/57%). RESULTS: The definitive version of the OHRQoL-DW scale with 28 items showed very good reliability, with Cronbach's alpha = 0.938. Good temporal stability of the questionnaire was demonstrated, and satisfactory results were obtained for divergent and convergent validity tests. Exploratory factorial analysis revealed four domains of oral health-related quality of life in denture wearers: physical, psychosocial, environmental and aesthetic. CONCLUSIONS: The OHRQoL-DW scale is a reliable and valid generic instrument for measuring the oral health-related quality of life in patients wearing dentures, which is one of the most important outcomes of oral health in prosthetic treatment.
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Salud Bucal , Calidad de Vida , Adulto , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Estudios Transversales , Reproducibilidad de los Resultados , DentadurasRESUMEN
Although being very effective in the treatment of diabetes and a few other conditions, metformin (MTF) cannot be tolerated by many patients due to gastrointestinal (GI) complaints. A number of risk factors for intolerance were identified, but many are still controversial or uninvestigated. The aim of this study was to further investigate possible risk factors for the occurrence of GI complaints in patients on MTF therapy. A cross-sectional design was used for this multicentric study on adult patients visiting 50 community pharmacies in Montenegro. The patients were surveyed by semi-structured questionnaire after a service of a pharmacist was delivered, and their drugs dispensed. Uni- and multi-variate regression methods were used for processing the data. In total 330 patients participated in the study. A higher body mass index (OR = 1.113, p = 0.003), living at a higher altitude (OR = 1.725, p = 0.000), anaemia (OR = 4.221, p = 0.008), and intestinal infection in the last 3 months (OR = 2.801, p = 0.006) increased the risk of GI complaints in patients on MTF therapy, while the use of statins was protective (OR = 0.204, p = 0.016). Each case of MTF intolerance should be carefully investigated for risk and protective factors, which could be potentially eliminated or augmented, respectively, and MTF withdrawal avoided.
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INTRODUCTION: Refractory status epilepticus (RSE) is a diagnosis that can be made when tonic-clonic status epilepticus (SE) and focal SE cannot be stopped by at least two anti-seizure medications after 30 and 60 minutes, respectively, from the time of commencement. It could result in mortality, loss of functionality, neurological deficiency, and other serious short- and long-term effects. AREAS COVERED: This narrative review covers original clinical studies of any design and case series investigating long-term outcomes of RSE recorded after at least a year from the SE onset. EXPERT OPINION: The future of a patient with RSE rests mostly on the long-term effects of this severe pathological condition, which may be accompanied with systemic complications like hyperthermia, hyperkalemia, acidosis, and/or stress cardiomyopathy. Younger patients with less severe RSE of shorter duration, particularly of the convulsive kind, are reported to have better long-term outcomes. Previous studies on the factors influencing the long-term outcomes of RSE, however, did not link the outcomes to treatment options for the condition. Such circumstances currently prevent making any definitive recommendations on the treatment of RSE until future research with adequate statistical power is completed.
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Estado Epiléptico , Humanos , Anticonvulsivantes/uso terapéutico , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/diagnóstico , Factores de Tiempo , Resultado del TratamientoRESUMEN
To satisfy the needs of pediatric and other patients with focal onset seizures who cannot swallow solid dosage forms of zonisamide, an oral liquid form of this drug is necessary in clinical practice. Although there are two oral suspensions of zonisamide with marketing authorization (MA), there are issues of availability and high cost which limit their use and inspire extemporaneous compounding. Extemporaneously compounded oral suspensions of zonisamide are prepared according to different formulas and vary in stability; therefore it is essential to test this characteristic. Bioequivalence of extemporaneously compounded oral suspensions has never been tested, and the efficacy and safety of zonisamide oral suspensions have generally not been demonstrated in clinical trials. As a narrow therapeutic window drug, zonisamide requires precision in dosing, which could be achieved only with dosage forms with established bioavailability, efficacy, and safety. In order to avoid underdosing and toxicity with zonisamide oral suspensions and utilize their full therapeutic potential, it is necessary to perform bioequivalence studies with each variation of extemporaneously compounded oral suspension and also clinical trials with both commercial and extemporaneous oral suspensions of zonisamide.
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Critical illness may disrupt nutritional, protective, immune, and endocrine functions of the gastrointestinal tract, leading to a state of gastrointestinal dysmotility. We aimed to identify factors associated with the occurrence of gastrointestinal dysmotility in critically ill patients. A cross-sectional retrospective study was conducted, using patient files as a source of data. The study included 185 critically ill patients treated in the intensive care unit of the University Clinical Center, Kragujevac, Serbia, from January 1, 2016, to January 1, 2022. Significant risk factors associated with some form of gastrointestinal dysmotility were acute kidney injury (with paralytic ileus, nausea, vomiting, and constipation), recent abdominal surgery (with ileus, nausea, vomiting, and constipation), mechanical ventilation (with ileus, and nausea), age (with ileus and constipation), and use of certain medication such as opioids (with ileus, gastro-esophageal reflux, nausea, vomiting, and constipation), antidepressants (with ileus, nausea, and vomiting), and antidiabetics (with ileus). On the other hand, Charlson comorbidity index had divergent effects, depending on the form of gastrointestinal dysmotility: it increased the risk of gastro-esophageal reflux but protected against ileus, nausea, and vomiting. In clonclusion, recognition of factors associated with gastrointestinal dysmotility should initiate preventative measures and, thus, accelerate the recovery of critically ill.
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OBJECTIVE: Although some of the positive effects of consulting a clinical pharmacologist when using complex treatment schedules have been demonstrated, the factors determining treatment outcomes are largely unknown. A main aim of this study was to identify and analyze the factors associated with the treatment outcomes in hospital patients in whom a therapeutic plan proposed by a clinical pharmacologist had been accepted and implemented. MATERIALS AND METHODS: The research was conducted as a retrospective cohort study on a random sample of 200 inpatients in the University Clinical Center Kragujevac, Serbia. The main outcome variables were i) in-hospital mortality, ii) inadequate clinical response to the therapy or pharmacological recommendations proposed by a clinical pharmacologist, iii) the total length of hospitalization, and iv) the length of hospitalization after consulting a clinical pharmacologist. The effect of putative predictors and confounders on the study outcomes were analyzed using multivariate regression models. RESULTS: Early integration of clinical pharmacologists in the course of patient treatment was associated with a reduction in the risk of a fatal outcome (OR = 1.146; 95% CI, 1.006 - 1.305; p = 0.040). Delay in consulting a clinical pharmacologist was associated with a longer overall length of patient hospitalization (B = 1.592; 95% CI, 1.100 - 2.084; p = 0.000). When the reasons for consulting a clinical pharmacologist involved the choice of drug or the occurrence of adverse drug reactions, the duration of hospitalization following the consultation was shorter by ~ 4 days (B = -4.337; 95% CI, -8.190 to -0.484; p = 0.028) and 12 days (B = -12.024; 95% CI, -19.108 to -4.940; p = 0.001), respectively. CONCLUSION: To achieve more favorable treatment outcomes in the case of difficult-to-treat hospital inpatients, clinical pharmacologists should be consulted early in the course of the disease, especially when the choice of drug is difficult, and the occurrence of adverse drug reactions is an important issue.