Outcomes of long-acting injectable antipsychotics use in pregnancy: A literature review.

BACKGROUND: Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy. Long-acting injectable (LAI) antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders, but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during pregnancy. AIM: To summarize relevant data on maternal, pregnancy, neonatal, and developmental outcomes from published cases of LAI antipsychotic use in pregnancy. METHODS: A literature search was performed through November 11, 2023, using three online databases: PubMed/MEDLINE, Scopus, and Web of Science. Case reports or case series that reported information about the outcomes of pregnancy in women who used LAI antipsychotics at any point in pregnancy, with available full texts, were included. Descriptive statistics, narrative summation, and tabulation of the extracted data were performed. RESULTS: A total of 19 publications satisfied the inclusion criteria: 3 case series, 15 case reports, and 1 conference abstract. They reported the outcomes of LAI antipsychotic use in 74 women and 77 pregnancies. The use of second-generation LAI antipsychotics was reported in the majority (n = 47; 61.0%) of pregnancies. First-generation LAI antipsychotics were administered during 30 pregnancies (39.0%). Most of the women (approximately 64%) had either satisfactory control of symptoms or no information about relapse, while approximately 12% of them had developed gestational diabetes mellitus. A minority of cases reported adverse outcomes such as stillbirth, spontaneous abortion, preterm birth, low birth weight, congenital anomalies, and neurological manifestations in newborns. However, there were no reports of negative long-term developmental outcomes. CONCLUSION: Currently available data seem reassuring, but further well-designed studies are required to properly evaluate the risks and benefits of LAI antipsychotic use during pregnancy.

Impact of Emergency Situations on the Level of Fear and Anxiety in Oncology Patients During Radiotherapy in a Developing Country.

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.

Factors affecting outcome in hospitalized patients treated according to recommendations from clinical pharmacologists.

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.

Predictors of Mortality in Early Neonatal Sepsis: A Single-Center Experience.

Background and Objectives: Early neonatal sepsis is associated with a significant mortality rate despite modern treatment strategies. Our aim was to identify risk factors contributing to the occurrence of death in newborns with early neonatal sepsis. Materials and Methods: We conducted a retrospective cross-sectional study that included newborns with early sepsis who received care in the intensive and semi-intensive care units at the Institute of Neonatology, Belgrade, Serbia. Newborns with early neonatal sepsis who died comprised the case group, whereas those who survived made up the control group. The diagnostic and therapeutic approach to the septic condition was carried out independently of this study, according to valid hospital protocols and current good practice guidelines. The influence of a large number of variables on the examined dichotomous outcome, as well as the mutual interaction of potential predictor variables, was examined by binary logistic regression. Results: The study included 133 pregnant women and 136 newborns with early neonatal sepsis, of which 51 (37.5%) died, while the remaining 85 newborns (62.5%) survived. Newborns who died had a statistically significantly lower birth weight compared to those who survived (882.8 ± 372.2 g vs. 1660.9 ± 721.1 g, p = 0.000). Additionally, compared to newborns who survived, among the deceased neonates there was a significantly higher proportion of extremely preterm newborns (74.5% vs. 22.4%, p = 0.000). The following risk factors for the occurrence of death in early neonatal sepsis were identified: low birth weight, sepsis caused by gram-negative bacteria, and the use of double-inotropic therapy and erythrocyte transfusion during the first week. Conclusions: Pediatricians should pay special attention to infants with early neonatal sepsis in whom any of the identified risk factors are present in order to prevent a fatal outcome.

Kounis Syndrome Associated With the Use of Diclofenac.

BACKGROUND: Diclofenac is a widely used analgesic, anti-inflammatory, antipyretic drug. In several case reports, its use was associated with the occurrence of Kounis syndrome. The aim of this review was to investigate and summarize published cases of Kounis syndrome suspected to be associated with the use of diclofenac. METHODS: Electronic searches were conducted in PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and the Serbian Citation Index. RESULTS: Twenty publications describing the 20 patients who met inclusion criteria were included in the systematic review. Specified patient ages ranged from 34 to 81 years. Eighteen (90.0%) patients were male. Five patients (25.0%) reported a previous reaction to diclofenac. Reported time from the used dose of diclofenac to onset of the first reaction symptoms ranged from immediately to 5 hours. Diclofenac caused both type I and type II Kounis syndrome, with the presence of various cardiovascular, gastrointestinal, dermatologic, and respiratory signs and symptoms. Most patients experienced hypotension (n = 15 [75.0%]) and chest pain (n = 12 [60.0%]). The most frequently reported finding on electrocardiogram was ST-segment elevations (n = 17 [85.0%]). Coronary angiogram showed normal coronary vessels in 9 patients (45.0%), with some pathologic findings in 8 patients (40.0%). CONCLUSION: Clinicians should be aware that Kounis syndrome may be an adverse effect of diclofenac. Prompt recognition and withdrawal of the drug, with treatment of both allergic and cardiac symptoms simultaneously, is important.

Amoxicillin-associated Stevens-Johnson syndrome or toxic epidermal necrolysis: systematic review.

Our aim was to explore and summarize available cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) suspected to be associated with amoxicillin reported in the literature. Electronic searches were conducted in several databases. Fifty-one publications describing a total of 64 patients who satisfied inclusion criteria were included in the review. The age of the patients ranged from 1.5-80 years (median: 24.5 years). TEN, SJS and SJS/TEN overlap were diagnosed in 30 (46.9%), 28 (43.8%) and 1 (1.6%) patients, respectively. SJS/TEN may occur promptly after administration of amoxicillin, but it could also be a delayed adverse effect. The total length of hospital stay ranged from 3-70 days (median: 16 days). Amoxicillin-induced SJS/TEN is accompanied by frequent occurrence of serious complications, long-term ocular and skin sequelae and high mortality rate. Clinicians should be aware that amoxicillin alone or combined with clavulanic acid can cause SJS/TEN in patients of all ages.

Review of compounds that exhibit radioprotective and/or mitigatory effects after application of diagnostic or therapeutic ionizing radiation.

PURPOSE: Exposure to ionizing radiation can be accidental or for medical purposes. Analyzes of the frequency of radiation damage in the general population, it has been determined that by far the most common are those that occur as a result of diagnostic or therapeutic procedures. Damage caused by radiation, either accidentally or for therapeutic purposes, can be reduced by the use of radioprotectors, mitigators or other therapeutic agents. A detailed research of the available literature shows that there is little systematized data of potentially radioprotective and/or mitigating effects of drugs from the personal therapy of patients during the application of therapeutic ionizing radiation. The aim of this paper is to present review of compounds, especially personal therapy drugs, that exhibit radioprotective and/or mitigating effects after the application of diagnostic or therapeutic ionizing radiation. CONCLUSIONS: Given the widespread use of ionizing radiation for diagnostic and therapeutic purposes, there is a clear need to create a strategy and recommendations of relevant institutions for the use of radioprotectors and mitigators in everyday clinical practice, with individual evaluation of the patient's condition and selection of the compounds that will show the greatest benefit in terms of radioprotection.

An outbreak of Legionnaires' disease in newborns in Serbia.

Legionnaires' disease is an atypical pneumonia caused by inhaling small droplets of water containing the bacterium Legionella spp. In newborns, it is a rare event, usually associated with water births and the use of air conditioning systems or air humidifiers. A nosocomial outbreak of Legionnaires' disease in the maternity ward of a secondary-care hospital in Arandjelovac, Serbia is described.Two male newborns were found to be infected with Legionnella pneumophila. On Days 7 and 6 of life, respectively, they were transferred to a tertiary-care hospital with signs of severe pneumonia which was radiologically confirmed. L. pneumophila was detected in tracheal secretions from both infants by RT-PCR, and its antigens were also positive in urine samples. The source of infection in the secondary-care hospital was the internal hot water heating system, and the main contributory factor to the emergence of the infection was the low temperature of the hot water which did not kill the bacteria during the available exposure time.These two cases highlight the importance of being cautious about possible Legionnaires' disease in maternity wards with outdated or irregularly maintained internal water supply systems. The adoption of official guidelines for the control and regular maintenance of water supply systems, including the multidisciplinary cooperation of all relevant parties, forms the basis for direct monitoring for Legionella and the prevention of new outbreaks.Abbreviations: BCYE: buffered charcoal yeast extract agar; GVPC: glycine vancomycin polymyxin cycloheximide agar; LD - Legionnaires' disease; TR-PCR: Reverse transcription polymerase chain reaction.

Possible association of methotrexate use with osteonecrosis of the jaw: Systematic review.

The aim was to search systematically, evaluate, and then summarize scientific literature about possible methotrexate-associated osteonecrosis of the jaw (ONJ), its signs and symptoms, diagnosis, treatment, and prognosis in adults. After registration at PROSPERO this systematic review was conducted and reported according to the PRISMA checklist. The following databases were systematically searched: MEDLINE, EBSCO, The Cochrane Central Register of Controlled Trials (Central), SCIndex, Scopus, Google Scholar and Registry of clinical studies with human participants. In total 9 studies with 14 patients were included in the review. All cases of ONJ associated with methotrexate were described in patients suffering from Rheumatoid arthritis (RA), and only about 40% of them were taking other concomitant medication described to be associated with ONJ (bisphosphonates). Both sexes were equally affected, and the patients were rather old (over 60 years if age), already taking methotrexate for more than 12 years on average. Antibiotics were ineffective in the treatment of ONJ; after stopping methotrexate, all lesions healed after several months on average; however, half of the cases required covering of the exposed bone with mucosal flap. Recurrence of the methotrexate-associated ONJ was not observed for at least two years after the lesions were healed. Methotrexate-associated ONJ is serious clinical condition that may occur in patients with RA, but given the small number of cases we have found in the literature, direct involvement of methotrexate in the development of ONJ remains elusive.

Development and Validation of Questionnaires on Professional Drivers' Knowledge and Attitudes About Various Medications' Influence on Driving Ability.

INTRODUCTION: Professional drivers' knowledge about driving-impairing medications is not satisfactory. The aim of this study was to develop and test the reliability and validity of the questionnaires designed to measure the knowledge and attitude of professional drivers about the influence of various medications on driving ability. METHODS: The questionnaires for assessing professional driver's knowledge (performance-based) and attitudes about influence of various medications on driving abilities were developed by creating the item pool, testing reliability and validity, and factor analysis. The study was conducted as a multicenter, cross-sectional study in Serbia and Bosnia and Herzegovina. The study population consisted of professional drivers, who filled out both questionnaires in three time intervals. RESULTS: Both questionnaires showed great internal consistency and temporal stability. Cronbach's Alpha for the first questionnaire was 0.984 and for the second it was 0.944. The Kaiser-Meyer-Olkin test for the first questionnaire confirmed sampling adequacy with its value of 0.964 and for the second questionnaire it was 0.933. Exploratory factor analysis of the questionnaire showed that three factors were revealed after rotation for the first questionnaire and they explained 78.0% of variance. Both questionnaires showed high degree of correlation between scores after the first and repeated administration, Spearman's rho coefficient of correlation for was 0.962 and 0.980. CONCLUSION: Based on the results of this study, we believe that both questionnaires are useful tools for testing professional drivers' knowledge and attitudes about the influence of medications on driving ability.

Epidemiology and risk factors for healthcare-associated infections caused by Pseudomonas aeruginosa.

Pseudomonas aeruginosa (PA) is a globally recognized cause of healthcare-associated infections (HAIs). The aim of our cross-sectional study, conducted in a Serbian tertiary care hospital, was to investigate clinical characteristics of HAIs caused by the PA, the prevalence of various drug-resistant phenotypes of this pathogen, and risk factors for their occurrence. Prolonged ICU stay and previous carbapenem administration were independent risk factors for HAIs caused by carbapenem-resistant PA, while HAIs caused by multidrug-resistant PA were more frequent in patients with prolonged stay in an ICU, who were previously hospitalized at another department and previously treated with aminoglycosides, fluoroquinolones or glycopeptides. The prolonged ICU stay was the only significant risk factor for HAIs caused by extensively drug-resistant PA. To decrease the incidence of HAIs caused by drug-resistant PA, a multifaceted approach is necessary, including staff education, antibiotic stewardship, improving hygiene, shortening hospitalization, and minimizing exposure to invasive medical procedures/devices.

Acute chemoradiotherapy toxicity in cervical cancer patients.

During radiotherapy treatment for cervical cancer, up to 84% of patients exhibit some form of acute radiation toxicity (ART). The primary aim of this clinical study is to determine the impact of angiotensin-converting enzyme (ACE) inhibitors, ß-blockers and other risk factors such as the patient's anatomical characteristics on ART emergence in patients with locally advanced cervical cancer treated by chemoradiotherapy. This is a combination of two nested case-control studies within the cohort of patients with locally advanced cervical cancer based on the analysis of potential risk factors for the onset of ART in patients treated with 3D conformal radiotherapy (3D-CRT) and 2D conventional radiotherapy (2D-RT), prospectively followed up from January 2017 to September 2018 in a tertiary care hospital. The ACE inhibitors and bladder volume were identified as factors that significantly affect the occurrence of ART in patients treated with 3D-CRT. In patients treated with 2D-RT, the factors that significantly affect the occurrence of ART were ACE inhibitors, body mass index (BMI), brachytherapy rectal and bladder dose. This study has shown that BMI, radiation dose received by the bladder and rectum are of exceptional importance for the occurrence of the ART and also that therapy with ACE inhibitors was associated with the decreased chances of the ART.

Preconditioning with PDE1 Inhibitors and Moderate-Intensity Training Positively Affect Systemic Redox State of Rats.

Taken into consideration that oxidative stress response after preconditioning with phosphodiesterase inhibitors (PDEIs) and moderate physical activity has still not been clarified, the aim of this study was to assess the effects of PDEIs alone or in combination with physical activity, on systemic redox status. The study was carried out on 96 male Wistar albino rats classified into two groups. The first group included animals exposed only to pharmacological preconditioning (PreC) maneuver (sedentary control (CTRL, 1 ml/day saline, n = 12), nicardipine (6 mg/kg/day of NIC, n = 12), vinpocetine (10 mg/kg/day of VIN, n = 12), and nimodipine (NIM 10 mg/kg/day of, n = 12). The second included animals exposed to preconditioning with moderate-intensity training (MIT) on treadmill for 8 weeks. After 5 weeks from the start of training, the animals were divided into four subgroups depending on the medication to be used for pharmacological PreC: moderate-intensity training (MIT+ 1 ml/day saline, n = 12), nicardipine (MIT+ 6 mg/kg/day of NIC, n = 12), vinpocetine (MIT+ 10 mg/kg/day of VIN, n = 12), and nimodipine (MIT+ 10 mg/kg/day of NIM, n = 12). After three weeks of pharmacological preconditioning, the animals were sacrificed. The following oxidative stress parameters were measured spectrophotometrically: nitrites (NO2 -), superoxide anion radical (O2 -), hydrogen peroxide (H2O2), index of lipid peroxidation (TBARS), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). Our results showed that PDE1 and MIT preconditioning decreased the release of prooxidants and improved the activity of antioxidant enzymes thus preventing systemic oxidative stress.

Predictors of antibiotic utilization among intensive care unit patients.

Increased antibiotic utilization in hospital is linked to higher total treatment costs, together with increased length of stay, surgery and emergency admission. The aim of our retrospective cohort study was to investigate predictors of antibiotic utilization per single patient from an intensive care unit (ICU) of a tertiary care, university hospital in Serbia. Average utilization of antibiotics per patient was 23.9 ± 20.4 defined daily doses (DDDs). Diagnosis of systemic infection increased antibiotics utilization per patient for 10.0 DDDs, positive blood culture for 5.4 DDDs, isolation of Pseudomonas spp. for 19.5 DDDs, isolation of Acinetobacter spp. for 6.3 DDDs and injury for 7.3 DDDs per patient. Each new day of hospitalization and each additional drug prescribed increased utilization for further 0.3 DDDs and 1.2 DDDs, respectively. Appropriate and limited use of antibiotics in ICU is of key importance for preserving their effectiveness and decrease of bacterial resistance.

Contemporary surgical management of drug-resistant focal epilepsy.

Introduction: Seizures, which could not be controlled by drug therapy, have profound negative influence on the quality of life of the affected person. If with clear locus of origin and accompanied by loss of consciousness, drug-resistant epilepsy could be treated by surgery.Areas covered: The aim of this article was to review current status of epilepsy surgery through description of the most important operative methods and narrative comparison of their benefits and harms. In total 1154 articles were retrieved from MEDLINE, SCOPUS, EBSCO, and SCINDEKS databases, and 78 included in the review. The review included systematic reviews, meta-analyses, clinical trials, observational studies on humans, case series, and case reports.Expert opinion: Sophisticated diagnostic methods nowadays offer much more precise localization of epileptogenic focus and detailed planning of a surgical procedure which will make minimal damage of neural pathways and structures essential for movements, speech, cognition, and emotions. Advent of perioperative care, and improved diagnostics and surgical techniques resulted with significant drop in rates of postoperative complications, long-term neurological deficit, and mortality in the last decade, while seizure freedom rate and quality of life increased.

Antimicrobial susceptibility among urinary Escherichia coli isolates from female outpatients: age-related differences.

OBJECTIVES: Urinary tract infections (UTIs) are common problems in women, and important reason for visiting primary care physicians, resulting in substantial financial burden to community. The aim of this study was to determine the resistance rates of E. coli to commonly prescribed antimicrobial drugs for community-acquired UTIs in women and to establish the association between age and resistance to antibiotics among isolates of E. coli from urine. METHODS: The study was designed as a retrospective cross-sectional study during the 5-years period. It was conducted on a sample of urinary tract isolates of E. coli taken from women with community-acquired UTIs. After prevalence of E. coli resistance to antibiotics was established, the analysis of risk factors for emergence of resistance was conducted. RESULTS: There were 10,734 isolates of E. coli, comprising 70.62% of all samples analyzed. E. coli was the most frequently resistant to ampicillin (54.68%), followed by trimethoprim-sulphamethoxazole (37.46%), first and second generation cephalosporins (cephalexin and cefaclor) (29.53% both), and ciprofloxacin (23.80%). Less than 50% of E. coli isolates was sensitive to all three tested antibiotics, and nearly 13% acquired triple-resistance. Prevalence of isolates resistant to two or three agents was higher in the subgroup of women older than 65 years. CONCLUSIONS: Empirical choice of antimicrobial agent for community-acquired non-complicated UTIs in women should be individualized on the basis of the patient's age, prevalence of resistance in the local community, and compliance history of the patient.

Effects of selective serotonin reuptake inhibitors on motility of isolated fallopian tube.

Selective serotonin reuptake inhibitors (SSRIs) affect the smooth muscle cells acting on voltage-dependent channels for Na+ , K+ and Ca2+ , but their action is tissue and species specific. The aim of our study was to investigate effects of selective serotonin reuptake inhibitors on motility of the isolated fallopian tubes. Isolated preparations of isthmus and ampoule were taken from fallopian tubes of 20 women during hysterectomy due to uterine fibroids and then tested for reactivity on increasing concentrations of selective serotonin reuptake inhibitors. Escitalopram (from 0.9 × 10-9  M/L to 1.4 × 10-6  M/L) produced concentration-dependent increase of spontaneous contractions of the isolated ampulla (EC50 = 1.20 ± 1.06 × 10-8  M/L, r = 0.580, P < 0.05) (F = 2.980, df1  = 6, df2  = 28, P < 0.05). Paroxetine (from 1.2 × 10-9  M/L to 5.1 × 10-5  M/L) produced concentration-dependent increase of spontaneous contractions of the isolated isthmus (EC50 = 7.01 ± 3.50 × 10-8  M/L, r = 0.500, P < 0.05) (F = 2.350, df1  = 9, df2  = 40, P < 0.05). The SSRIs differ among themselves in regard to their potential to affect motility of the fallopian tubes. Escitalopram and paroxetine have clear stimulating effect which may interfere with functioning of the fallopian tubes, and potentially impair fertility if taken by women in reproductive period of life. The other SSRIs tested in the study did not produce significant effect throughout the concentration range used in the experiments.

Clinical Pharmacokinetics of Second-Generation Triazoles for the Treatment of Invasive Aspergillosis and Candidiasis.

Second-generation triazoles were developed in response to the quest for more efficacious and safer therapeutic options for the treatment of severe systemic aspergillosis and candidiasis. These agents include voriconazole, posaconazole, isavuconazole, and ravuconazole. The aim of this review was to present and compare the pharmacokinetic characteristics of second-generation triazoles for the treatment of invasive aspergillosis and candidiasis, emphasizing their clinical implications. The MEDLINE, Scopus, EBSCO, Google Scholar, and SCIndeks databases were searched using advanced search options, including the names of second-generation triazoles and pharmacokinetic terms as keywords. The intravenous administration of voriconazole, posaconazole, and isavuconazole results in stable pharmacokinetics of these drugs, with mostly predictable variations influenced by common and usually known factors in routine clinical settings. The high oral bioavailability of isavuconazole and, to some extent, voriconazole makes them suitable for intravenous-to-oral switch strategies. Except for intravenous voriconazole (due to the accumulation of the toxic vehicle hydroxypropyl betadex), dose reduction of second-generation triazoles is not needed in patients with renal failure; patients with hepatic insufficiency require dose reduction only in advanced disease stages. The introduction of therapeutic drug monitoring could aid attempts to optimize the blood concentrations of triazoles and other drugs that are known to or that possibly interact, thus increasing treatment efficacy and safety. There is a need for new studies that are designed to provide useful data on second-generation triazole pharmacokinetics, particularly in special circumstances such as central nervous system and ocular infections, infections in newborns and infants, and in subjects with genetic polymorphisms of metabolizing enzymes.

Pharmacokinetics of Vancomycin in Patients with Different Renal Function Levels.

There are many determinants of vancomycin clearance, but these have not been analyzed separately in populations with different levels of renal function, which could be why some important factors have been missed. The aim of our study was to compare the pharmacokinetic parameters and factors that may affect vancomycin pharmacokinetics in groups of patients with normal renal function and in those with chronic kidney failure. The study used a population pharmacokinetic modeling approach, based on plasma vancomycin concentrations and other data from 78 patients with chronic kidney failure and 32 patients with normal renal function. The model was developed using NONMEM software and validated by bootstrapping. The final model for patients with impaired kidney function was described by the following equation: CL (L/h) = 0.284 + 0.000596 x DD + 0.00194 x AST, and that for the patients with normal kidney function by: CL (L/h) = 0.0727 + 0.205 x FIB. If our results are confirmed by new studies on two similar populations, these factors could be considered when dosing vancomycin in patients with chronically damaged kidneys, as well as in patients with normal kidneys who frequently require high doses of vancomycin.

Investigational cannabinoids in seizure disorders, what have we learned thus far?

INTRODUCTION: The anticonvulsant activity of cannabinoids attracted much attention in the last decade. Cannabinoids that are currently investigated with the intention of making them drugs for the treatment of epilepsy are cannabidiol, cannabidivarin, Δ9-tetrahydrocannabivarin, and Δ9-tetrahydrocannabinolic acid. AREAS COVERED: In this review, the authors look at the results of preclinical and clinical studies with investigational cannabinoids. Relevant literature was searched for in MEDLINE, SCOPUS, EBSCO, GOOGLE SCHOLAR, and SCINDEX databases. EXPERT OPINION: Preclinical studies confirmed anticonvulsant activity of cannabidiol and cannabidivarin in a variety of epilepsy models. While the results of clinical trials with cannabidivarin are still awaited, cannabidiol showed clear therapeutic benefit and good safety in patients with therapy-resistant seizures associated with Dravet syndrome and in patients with Lennox-Gastaut syndrome who have drop seizures. However, the full therapeutic potential of cannabinoids in treatment-resistant epilepsy needs to be investigated in the near future.