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ABSTRACT: An increase in blood lipoprotein (a) [Lp(a)] levels, mostly genetically determined, has been identified as an independent risk factor of atherosclerotic cardiovascular disease. No drug has yet been approved that markedly lowers Lp(a) and thereby reduces residual cardiovascular risk. The aim of this article was to critically review the evidence from clinical development studies to date on the efficacy and safety of new RNA-based therapeutics for targeted lowering of Lp(a). PubMed/MEDLINE, Scopus, Web of Science, and ClinicalTrials.gov were searched without any language or date restriction up to November 5, 2022, and a total of 12 publications and 22 trial records were included. Several drugs were found that are currently in various stages of clinical development, such as the antisense oligonucleotide pelacarsen and the small interfering RNA molecule olpasiran and drugs coded as SLN360 and LY3819469. Among them, pelacarsen has progressed the most, currently reaching phase 3. All these drugs have so far shown satisfactory pharmacokinetic properties, consistently high and stable, dose-dependent efficacy in lowering Lp(a) even by more than 90%, with an acceptable safety profile in subjects with highly elevated Lp(a). In addition, reports of early clinical trials with pelacarsen imply a promising suppressive effect on key mechanisms of atherogenesis. Future research should focus on confirming these beneficial clinical effects in patients with lower average Lp(a) levels and clearly demonstrating the association between lowering Lp(a) and reducing adverse cardiovascular outcomes.
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Aterosclerose , Doenças Cardiovasculares , Humanos , Lipoproteína(a) , RNA/uso terapêutico , Fatores de Risco , Oligonucleotídeos Antissenso/efeitos adversos , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controleRESUMO
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.
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Sepse Neonatal , Sepse , Lactente , Recém-Nascido , Humanos , Feminino , Gravidez , Estudos Retrospectivos , Estudos Transversais , Peso ao NascerRESUMO
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.
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Paroxetina , Inibidores Seletivos de Recaptação de Serotonina , Antidepressivos/farmacologia , Ansiedade , Feminino , Fertilidade , Humanos , Masculino , Paroxetina/efeitos adversos , Gravidez , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversosRESUMO
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.
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Acetaminofen/efeitos adversos , Síndrome de Stevens-Johnson/epidemiologia , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores de Risco , Síndrome de Stevens-Johnson/tratamento farmacológico , Síndrome de Stevens-Johnson/etiologia , Resultado do TratamentoRESUMO
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.
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Tubas Uterinas/efeitos dos fármacos , Tubas Uterinas/fisiologia , Movimento/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Adulto , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Background: Premature rupture of membranes (PROM) is defined as the leakage of amniotic fluid before the onset of labor and delivery contractions. Some studies found that women who experienced PROM had significantly lower vitamin C blood levels than those who did not, while others found no significant differences. Previous systematic reviews and meta-analyses on the efficacy of vitamin C in the prevention of PROM had conflicting results. Aims: Conduct a systematic review and meta-analysis to determine if there was a significant difference in vitamin C blood levels in women who had PROM versus the control group who did not and to determine if vitamin C supplements could help prevent it. Study Design: Systematic review and meta-analysis. Methods: We registered our protocol with PROSPERO (CRD42022371644). We searched PubMed/MEDLINE, Web of Science, and Scopus through February 15, 2024. Additionally, backward and forward citation searches were conducted. Studies were selected based on predetermined inclusion and exclusion criteria. Meta-Essentials: Workbooks for Meta-Analysis (version 1.5) was used for analysis. Results: Twenty-five studies (26 reports) met all eligibility criteria, with 18 studies (18 reports) assessing vitamin C levels and seven studies (eight reports) evaluating efficacy. Women with PROM, whether preterm or term, had significantly lower vitamin C levels [Hedges' g, -1.48; 95% confidence interval (CI): -2.82, -0.14; p = 0.020; I2 = 94.08%) and specifically preterm PROM after removing the outlying study [Hedges' g, -1.29; 95% CI: -1.85, -0.73; p < 0.001; I2 = 87.35%). Vitamin C supplementation significantly reduced the risk of preterm or term PROM [risk ratio (RR), 0.57; 95% CI: 0.39, 0.81; p < 0.001; I2 = 12.17%), particularly for preterm PROM (RR, 0.67; 95% CI: 0.45, 0.99; p = 0.001; I2 = 0.00%). There were no significant differences in vitamin C levels between women with term PROM and controls, and there were no differences in the risk of developing term PROM between women taking vitamin C supplements and controls. Results were not robust in all sensitivity analyses. Conclusion: Women with PROM, particularly those who developed it preterm, appear to have significantly lower vitamin C levels, and vitamin C supplementation appears to be effective in reducing the risk of PROM, particularly preterm PROM. More high-quality studies with low risk of bias, more homogenous, and larger samples are needed to confirm these findings.
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Ácido Ascórbico , Suplementos Nutricionais , Ruptura Prematura de Membranas Fetais , Feminino , Humanos , Gravidez , Ácido Ascórbico/uso terapêutico , Ácido Ascórbico/análise , Suplementos Nutricionais/estatística & dados numéricos , Ruptura Prematura de Membranas Fetais/prevenção & controleRESUMO
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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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.
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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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OBJECTIVE: Antidepressant-induced pancreatitis is a rare, albeit serious, adverse effect, with a frequency of occurrence that is not equally distributed among antidepressant drugs. The goal of this study was to investigate the association and causal relationship between mirtazapine treatment of patients with depression and pancreatitis. METHODS: The study was designed as a systematic review of the literature, accompanied by the description of a new case of mirtazapine-associated acute pancreatitis. RESULTS: Nine cases of mirtazapine-associated pancreatitis have been reported, involving 7 female patients and 2 male patients with a mean age of 46.4 years (range: 26 to 83 y of age). All of the patients were hospitalized, with an average length of stay of 16.2 days (range: 3 to 34 d). In 6 cases, "de-challenge" followed by improvement was reported. The patients for whom the outcome was reported (7 of 9) recovered completely. CONCLUSION: Although a rare adverse effect, mirtazapine-induced pancreatitis should be considered when patients taking mirtazapine report abdominal discomfort.
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Depressão , Pancreatite , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Mirtazapina/uso terapêutico , Doença Aguda , Depressão/tratamento farmacológico , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Antidepressivos/efeitos adversos , Mianserina/efeitos adversos , Antidepressivos Tricíclicos/efeitos adversosRESUMO
BACKGROUND: Cerliponase alfa is an orphan drug approved for the treatment of late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2). AIM: Our goal was to assess the cost-effectiveness of cerliponase alfa in patients with CLN2 in the socioeconomic context of the Republic of Serbia in contrast to symptomatic therapy. METHOD: For this study, a forty-year horizon and the perspective of the Serbian Republic Health Insurance Fund were used. Quality-adjusted life years gained with cerliponase alfa and comparator, as well as direct treatment costs, were the study's key outcomes. The creation and simulation of a discrete-event simulation model served as the basis for the investigation. Monte Carlo microsimulation was performed on a sample of 1000 virtual patients. RESULTS: When compared to symptomatic therapy, cerliponase alfa treatment was not cost-effective and was linked to negative net monetary benefit regardless of when the illness signs started. CONCLUSION: Cerliponase alfa is not more economical than symptomatic therapy for the treatment of CLN2 when using typical pharmacoeconomic analysis. Cerliponase alfa has been shown to be effective but more has to be done to make it accessible to all CLN2 patients.
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Lipofuscinoses Ceroides Neuronais , Tripeptidil-Peptidase 1 , Humanos , Lipofuscinoses Ceroides Neuronais/tratamento farmacológico , Dipeptidil Peptidases e Tripeptidil Peptidases/uso terapêuticoRESUMO
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.
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Antipsicóticos , Esquizofrenia , Humanos , Esquizofrenia/tratamento farmacológico , Antipsicóticos/uso terapêutico , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/uso terapêutico , JejumRESUMO
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.
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Síndrome de Stevens-Johnson , Humanos , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Síndrome de Stevens-Johnson/complicações , Síndrome de Stevens-Johnson/diagnóstico , Amoxicilina/efeitos adversos , Estudos RetrospectivosRESUMO
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.
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Diclofenaco , Síndrome de Kounis , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Diclofenaco/efeitos adversos , Síndrome de Kounis/diagnóstico , Síndrome de Kounis/etiologia , Eletrocardiografia , Angiografia Coronária/efeitos adversosRESUMO
BACKGROUND: Niemann-Pick disease type C (NP-C) is a progressive neurodegenerative disorder with early infantile (< 2 years), late infantile (2-6 years), juvenile (7-15 years) and adolescent (> 15 years) onset. The mainstay of therapy for NP-C patients with neurological symptoms is miglustat, a drug that may modify the course of the disease. AIM: Our aim was to evaluate the cost-effectiveness of miglustat in comparison to symptomatic therapy in patients with NP-C in the socio-economic settings of the Republic of Serbia, an upper-middle-income European economy. METHOD: The perspective of the Serbian Republic Health Insurance Fund was chosen for this study, and the time horizon was eighty years. The main outcomes of the study were quality-adjusted life years gained with miglustat and comparator, and direct costs of treatment. The study was conducted through the generation and simulation of the Discrete-Event Simulation model. The model results were obtained after Monte Carlo microsimulation of a sample with 1000 virtual patients. RESULTS: Treatment with miglustat was not cost-effective when compared with symptomatic therapy and was associated with negative values of net monetary benefit regardless of the onset of neurological manifestations (- 110,447,627.00 ± 701,614.00 RSD, - 343,871,695.00 ± 2,577,441.00 RSD, - 1,397,908,502.00 ± 23,084,235.00 RSD and - 2,953,680,879.00 ± 33,297,412.00 RSD) for early infantile, late infantile, juvenile and adolescent cohorts, respectively). CONCLUSION: When traditional pharmacoeconomic evaluation is employed, miglustat is not a cost-effective option in comparison to symptomatic therapy for the treatment of NP-C. However, given the proven efficacy of miglustat, there is a need to find ways to make this drug available to all patients with NP-C.
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Doença de Niemann-Pick Tipo C , Adolescente , Humanos , Doença de Niemann-Pick Tipo C/diagnóstico , Doença de Niemann-Pick Tipo C/tratamento farmacológico , Análise Custo-Benefício , Inibidores Enzimáticos/uso terapêutico , 1-Desoxinojirimicina/uso terapêutico , 1-Desoxinojirimicina/efeitos adversosRESUMO
The aim of this systematic review was to determine the causal role of Erysipelatoclostridium ramosum in specific invasive infections in humans, and to assess the clinical outcome of antibiotic therapy used to treat them. Several electronic databases were systematically searched for clinical trials, observational studies or individual cases on patients of any age and gender with a systemic inflammatory response syndrome (SIRS) due to E. ramosum isolated from body fluids or tissues in which it is not normally present. Only reports identifying E. ramosum as the only microorganism isolated from a patient with SIRS were included. This systematic review included 15 studies reporting 19 individual cases in which E. ramosum caused invasive infections in various tissues, mainly in immunocompromised patients. E. ramosum was most often isolated by blood cultures and identified by specific biochemical tests. Severe infections caused by E. ramosum were in most cases effectively treated with antibiotics, except in two patients, one of whom died. More than one isolate of E. ramosum exhibited 100% susceptibility to metronidazole, amoxicillin/clavulanate and piperacillin/tazobactam. On the other hand, individual resistance of this bacterium to penicillin, ciprofloxacin, clindamycin, imipenem and ertapenem was reported. This systematic review confirmed the clinical relevance of E. ramosum as a cause of a number of severe infections mainly in immunocompromised inpatients. Metronidazole and meropenem appear to be the antibiotics of choice that should be used in combination or as monotherapy to treat E. ramosum infections, depending on the type and severity of the infection.
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Antibacterianos/farmacologia , Firmicutes/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Humanos , Testes de Sensibilidade MicrobianaRESUMO
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.
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Infecções por Corynebacterium , Corynebacterium , Aminoglicosídeos , Antibacterianos/uso terapêutico , Corynebacterium/genética , Infecções por Corynebacterium/tratamento farmacológico , Humanos , Testes de Sensibilidade MicrobianaRESUMO
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.
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Interações Medicamentosas , Miastenia Gravis/tratamento farmacológico , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
The aim of this study was to compare cost-utility of tafenoquine (TQ) and primaquine (PQ) for a radical cure (prevention of relapse) of Plasmodium vivax (PV) malaria in Serbia using A five-state, 1-month cycle Markov model. The perspective of Republic Health Insurance Fund was chosen, and the time horizon was 10 years. The model results were obtained after Monte Carlo microsimulation of a sample with 1000 virtual patients. After base case analysis PQ was dominated by TQ, as the net monetary benefit was positive (20,713.84 ± 7,167.46 RSD (99% CI) (174.95 ± 60.54 )) and incremental cost-effectiveness ratio was below the willingness-to-pay line of 1 Serbian gross national product per capita per quality-adjusted life year gained. Multiple one-way sensitivity analysis and probabilistic sensitivity analysis confirmed the results of the base case simulation. In conclusion, TQ was cost-effective in comparison to PQ for radical cure of PV malaria in socio-economic settings of a South-Eastern European country.
Assuntos
Aminoquinolinas/economia , Antimaláricos/economia , Análise Custo-Benefício , Malária Vivax/tratamento farmacológico , Primaquina/economia , Aminoquinolinas/uso terapêutico , Antimaláricos/uso terapêutico , Humanos , Cadeias de Markov , Método de Monte Carlo , Primaquina/uso terapêutico , Recidiva , SérviaRESUMO
Objective of this systematic review was to establish whether and what invasive infections in humans were caused by Kocuria kristinae, and to evaluate outcomes of administered antibiotic treatment. MEDLINE, EBSCO, SCOPUS, SCINDEKS and GOOGLE SCHOLAR were systematically searched for primary case reports or case series describing invasive infections with K. kristinae. K. kristinae is a pathogen microorganism that could cause invasive infections of various tissues in patients of any age. Majority of the patients had K. kristinae isolated from blood. It was also found in peritoneal fluid, pus, sputum, synovial fluid, bile, fluid from abdominal abscess, throat swab, urine catheter tip and mid-stream urine. Antibiotic treatment was almost universally effective, with only one death reported. Susceptibility was highest to vancomycin, linezolid, rifampicin, teicoplanin, tigecycline, cefotaxime, ampicillin/sulbactam, minocycline and meropenem. Initial treatment of Kocuria kristinae infections should involve parenteral vancomycin in combination with some other antibiotic to which it is susceptible.