Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2.

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.

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.

Testing of new instrument for measuring quality and diversity of nutrition in pregnancy.

OBJECTIVES: Our aim was construction and development of a new questionnaire for assessing the quality and diversity of nutrition of pregnant women. MATERIAL AND METHODS: This was a cross-sectional study. The novel questionnaire was developed through eight steps according with internationally accepted guidelines for questionnaire development. The questionnaire with 18 questions and answers according to the Likert's scale was created and called Balkan Food Quality and Diversity in Pregnancy Questionnaire-18 (BFQDPQ-18). Reliability testing and factor analysis of BFQDPQ-18 were carried out on a sample of 382 women in the third trimester of pregnancy whose pregnancy control and monitoring were performed at the Clinic for Gynecology and Obstetrics of the Clinical Center in Kragujevac, Serbia. RESULTS: The first test of reliability indicated high levels of internal consistency, with the Cronbach's alpha of 0.85 of the BFQDPQ-18. After dividing the BFQDPQ-18 into two parts of nine questions each by split-half method, the Cronbach's alphas were 0.799 and 0.716. The Kaiser-Meyer-Olkin Measure of Sampling Adequacy (KMO) was 0.878, and the Bartlett's test of sphericity: 1,892.206, p < 0.000. Factor analysis revealed four factors explained in total 51.99% of the variance: mean meal and snack, foods with a low degree of industrial processing, subjective assessment of dietary quality and starchy foods. CONCLUSIONS: The final version of the BFQDPQ-18 showed high reliability and good psychometric properties, so we believe it could be useful instrument for assessing the quality of nutrition of pregnant women.

Meta-analysis of peripheral insulin-like growth factor 1 levels in schizophrenia.

OBJECTIVE: We aimed to investigate if there is a significant difference in peripheral insulin-like growth factor 1 (IGF-1) levels between schizophrenia patients and healthy controls and to determine whether a difference exists before and after initiation of antipsychotics. METHODS: PubMed/MEDLINE, Scopus, and Web of Science were searched up to March 27, 2022. Original clinical studies of any type that reported peripheral blood, serum or plasma IGF-1 levels measured after fasting in schizophrenia patients and/or healthy control group were selected based on inclusion and exclusion criteria. Data were analyzed using Meta-Essentials: Workbooks for meta-analysis and pooled through random-effects meta-analyses. RESULTS: Twelve publications met eligibility criteria. Schizophrenia patients under antipsychotic treatment had significantly lower peripheral IGF-1 levels compared to healthy controls (n = 632, Hedges' g -0.42, 95% CI from -0.79 to -0.04, p = .006, I2  = 70.38%), while no significant difference was found between schizophrenia patients regardless of the antipsychotic treatment status and healthy controls, as well as between antipsychotic naïve or free schizophrenia patients and healthy controls, and before and after initiation of antipsychotic treatment. However, high heterogeneity was observed and its potential sources in some of the subgroup analyses included sample type and region. CONCLUSIONS: Schizophrenia patients under antipsychotic treatment seem to have lower peripheral IGF-1 levels compared to healthy controls. Additional studies with larger and more homogenous samples are needed to confirm these findings.

Factors associated with fetal growth restriction and small for gestational age newborns.

OBJECTIVES: To identify risk factors that contribute to the occurrence of fetal growth restriction (FGR) and small for gestational age (SGA) and quantify the strength of their impact. MATERIAL AND METHODS: This study was designed as a retrospective-prospective observational cohort study conducted on pregnant women at the Clinic for Gynecology and Obstetrics at the University Clinical Centre Kragujevac, Serbia. We measured the intrauterine degree of fetal development through the estimated fetal weight (EFW) on ultrasound examination, which was calculated using Hadlock's formula 3. Fetuses whose EFW was below the 10th percentile on the World Health Organization (WHO) fetal growth charts adjusted for gender and gestational age were classified as FGR fetuses, while newborns weighing less than the 10th percentile were considered SGA. RESULTS: The study included 320 pregnant women with an average age of 30.3 ± 5.5 years who gave birth to 332 newborns. The results of univariate and multivariate stepwise backward conditional binary logistic regression showed that the occurrence of FGR during the second trimester was more likely in pregnant women with lower body height and proteinuria. The risk factors for the occurrence of FGR during the third trimester were lower body height and proteinuria, while iron supplementation had a protective effect. SGA newborns were more common in pregnant women who were shorter, had proteinuria, used corticosteroids, or smoked during pregnancy. CONCLUSIONS: Clinicians should pay special attention to pregnant women with lower body height, proteinuria, who smoke and use corticosteroids in order to prevent FGR and SGA.

The effects of selective serotonin reuptake inhibitors on male and female fertility: a brief literature review.

Objective: The aim of this review was to determine whether selective serotonin reuptake inhibitors (SSRIs) affect the ability to conceive in men and women of reproductive age, as well as to find out whether there are certain differencies between them in terms of effects on fertility. Methods: Our review was based on systematic search of literature in four online databases: Medline (PubMed), Scopus, Web of Science and SCIndex (Serbian Citation Index). Results: Several clinical studies reported that SSRIs can decrease the number and viability of sperm, and cause a disruption of their morphological structure. Regarding the effect of these antidepressants on female fertility, some experimental findings suggest that paroxetine and escitalopram may have a negative effect on the ability to conceive due to their stimulatory effect on fallopian tube motility. However, several observational studies favor the use of SSRIs in women with depression/anxiety undergoing in vitro fertilization (IVF) given their efficiency in suppressing these unpleasant symptoms without a relevant negative impact on IVF outcomes. Conclusions: SSRIs should be avoided male patients of reproductive age who wish to conceive, while the use of these antidepressants seems to be justified in women with depression or anxiety who have undergone IVF.Key pointsSSRIs could cause dose and duration-dependent reversible adverse effects on male fertility parameters.In depressed or anxious male patients of reproductive age who wish to conceive mirtazapine or bupropion should be used because of their lower potential to cause sexual side effects.The results of certain experimental studies indicate that paroxetine and escitalopram may have a negative effect on the fertility of female patients.The use of SSRIs in women with depression or anxiety who have undergone IVF seems to be justified, because these psychiatric disorders reduce the likelihood of becoming pregnant.

Risk factors for potential drug-drug interactions in patients with myasthenia gravis.

OBJECTIVES: Our aim was to determine risk factors for and frequency of potential drug-drug interactions (pDDIs) among hospitalized patients with myasthenia gravis (MG). METHODS: This was a retrospective cross-sectional study of the-first time hospitalized MG patients or patients hospitalized because of the exacerbation of MG at the Neurology Clinic of the Clinical Center of Serbia, Belgrade. Medical records and discharge summaries of hospitalized MG patients over a 10-year period were reviewed. The pDDIs were identified by means of Micromedex, and multivariate regression methods were used to reveal potential predictors of number of pDDIs per patient. RESULTS: The study included 687 patients with MG. In total, 2041 pDDIs were detected in 608 (88.5%) patients. Among the discovered pDDIs, 329 different pDDIs were observed. The most frequent pDDIs were pyridostigmine-prednisone (487patients/70.9%) and aspirin-prednisone (90 patients/13.1%) classified as moderate, and enalapril-potassium chloride (71patients/10.3%) classified as major pDDI. Five drugs (aspirin, insulin, prednisone, cyclosporine, metformin) were responsible for 22.6% of different pDDIs. Dyspnea, generalized form of MG, diabetes mellitus, hypertension, total number of drugs-used, use of antiplatelets were identified as the relevant risk factors for total number of pDDIs (R2 = 0.626,F = 73.797, p < 0.001), while age of patients and history of cancer were inversely correlated with such an outcome. CONCLUSION: The frequency of the pDDIs in hospitalized MG patients is high, and adversely influenced by dyspnea, generalized MG, diabetes mellitus, hypertension, total number of drugs-used and use of antiplatelets.

A review of published cases of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with the use of acetaminophen.

PURPOSE: Acetaminophen (paracetamol) is a widely used analgesic and antipyretic. In several studies, its use was associated with the occurrence of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). This narrative review aimed to explore and summarise available cases of SJS/TEN suspected to be associated with acetaminophen reported in the literature. MATERIALS AND METHODS: Electronic searches were conducted in PubMed/MEDLINE, Web of Science, Scopus and Serbian Citation Index (SCIndeks). Case reports or case series which reported detailed clinical description of the patients diagnosed with SJS, TEN or SJS/TEN overlap which was caused or suspected to be most likely caused by acetaminophen with available full text were included in the review. RESULTS: Twenty-nine publications describing a total of 36 patients which satisfied inclusion criteria were included in the review. The age of the patients ranged from 3 to 77 years (median: 32.5 years). There were 15 female (41.7%) and 15 male (41.7%) patients, while for 6 patients (16.7%) gender was not reported. TEN, SJS and SJS/TEN overlap were diagnosed in 24 (66.7%), 10 (27.8%) and 2 (5.6%) patients, respectively. Reported time from the first dose of acetaminophen to the onset of the first symptoms of SJS/TEN ranged from promptly to 21 days, with a median of 3 days. Use of some form of supportive and symptomatic care was reported in 28 patients (77.8%). Systemic corticosteroids were reported to be administered in 25 patients (69.4%) and intravenous immunoglobulin in 16 patients (44.4%). All patients survived. Long-term consequences (sequelae) were reported in 5 patients (13.9%). CONCLUSIONS: Clinicians should be aware that SJS/TEN may be an adverse effect of acetaminophen and keep in mind that its prompt recognition and withdrawal of the culprit drug along with supportive care is of utmost importance.

Antimicrobial treatment of Corynebacterium striatum invasive infections: a systematic review.

The aim of this study was to establish an evidence-based guideline for the antibiotic treatment of Corynebacterium striatum infections. Several electronic databases were systematically searched for clinical trials, observational studies or individual cases on patients of any age and gender with systemic inflammatory response syndrome, harboring C. striatum isolated from body fluids or tissues in which it is not normally present. C. striatum had to be identified as the only causative agent of the invasive infection, and its isolation from blood, body fluids or tissues had to be confirmed by one of the more advanced diagnostic methods (biochemical methods, mass spectrometry and/or gene sequencing). This systematic review included 42 studies that analyzed 85 individual cases with various invasive infections caused by C. striatum. More than one isolate of C. striatum exhibited 100% susceptibility to vancomycin, linezolid, teicoplanin, piperacillin-tazobactam, amoxicillin-clavulanate and cefuroxime. On the other hand, some strains of this bacterium showed a high degree of resistance to fluoroquinolones, to the majority majority of ß-lactams, aminoglycosides, macrolides, lincosamides and cotrimoxazole. Despite the antibiotic treatment, fatal outcomes were reported in almost 20% of the patients included in this study. Gene sequencing methods should be the gold standard for the identification of C. striatum, while MALDI-TOF and the Vitek system can be used as alternative methods. Vancomycin should be used as the antibiotic of choice for the treatment of C. striatum infections, in monotherapy or in combination with piperacillin-tazobactam. Alternatively, linezolid, teicoplanin or daptomycin may be used in severe infections, while amoxicillin-clavulanate may be used to treat mild infections caused by C. striatum.

SMILES-based QSAR model for arylpiperazines as high-affinity 5-HT(1A) receptor ligands using CORAL.

A predictive quantitative structure - activity relationships model of arylpiperazines as high-affinity 5-HT(1A) receptor ligands was developed using CORAL software (http://www.insilico.eu/CORAL). Simplified molecular input-line entry system (SMILES) was used as representation of the molecular structure of the arylpiperazines. The balance of correlations was used in the Monte Carlo optimization aimed to build up optimal descriptors for one-variable models. The robustness of this model has been tested in four random splits into the sub-training, calibration, and test set. The obtained results reveal good predictive potential of the applied approach: correlation coefficients (r²) for the test sets of the four random splits are 0.9459, 0.9249, 0.9473 and 0.9362.

SMILES-based QSAR models for the calcium channel-antagonistic effect of 1,4-dihydropyridines.

The activity of 72 1,4-dihydropyridines as calcium channel antagonists was examined. The simplified molecular input-line entry system (SMILES) was used as representation of the molecular structure of the calcium channel antagonists. Quantitative structure-activity relationships (QSARs) were developed using CORAL software (http://www.insilico.eu/CORAL) for four random splits of the data into the training and test sets. Using the Monte Carlo method, the CORAL software generated the optimal descriptors for one-variable models. The reproducibility of each model was tested performing three runs of the Monte Carlo optimization. The obtained results reveal good predictive potential of the applied approach: The correlation coefficients (r(2) ) for the test sets of the four random splits are 0.9571, 0.9644, 0.9836, and 0.9444.