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.

A model to determine factors influencing intraoperative complications in sleeve gastrectomy.

Objective: The study presents a logistic regression model describing the factors leading to intraoperative complications in laparoscopic sleeve gastrectomy (LSG) and a detailed description of the intraoperative complications that occurred in our operations. Material and methods: The study was designed as a retrospective and cohort study. It includes patients who underwent laparoscopic sleeve gastrectomy between January 2008 and December 2020. Results: The study included 257 patients. The mean (SD) age of all patients included in the study was 40.28 (9.58) years. The body mass index of our patients ranged from 31.2 to 86.6 kg/m2. The Stepwise Backward model was used (Cox and Snell R2 = 0.051, Nagelkerke R2 = 0.072, Hosmer-Lemesxow χ2 = 1.968, df = 4, p = 0.742, overall model accuracy of 70.4%). The model shows that pre-operative diabetes mellitus or hypertension Stage 3 significantly increases the probability or risk of intraoperative complications. Conclusions: The study shows which intraoperative complications occur in LSG, how they can be remedied and which factors can lead to them and influence the outcome of the operation itself. The recognition and successful treatment of intraoperative complications are very important as they reduce the number of reoperations and treatment costs.

Objetivo: El estudio presenta un modelo de regresión logística que describe los factores que conducen a las complicaciones intraoperatorias en la gastrectomía en manga laparoscópica (LSG) y una descripción detallada de las complicaciones intraoperatorias que ocurrieron en nuestras operaciones. Material y métodos: Estudio de cohorte retrospectivo. Incluye pacientes que se sometieron a LSG entre enero de 2008 y diciembre de 2020. Resultados: El estudio incluyó a 257 pacientes. La edad media (DE) de los pacientes del estudio fue de 40.28 (9.58) años. El índice de masa corporal de nuestros pacientes osciló entre 31.2 y 86.6 kg/m2. Se utilizó el modelo Stepwise Backward (Cox y Snell R2 = 0.051, Nagelkerke R2 = 0.072, Hosmer-Lemesxow χ2 = 1.968, gl = 4, p = 0.742, precisión global del modelo del 70.4%). El modelo muestra que la diabetes mellitus o hipertensión preoperatoria en estadio 3 aumenta significativamente la probabilidad de complicaciones intraoperatorias. Conclusiones: El estudio muestra qué complicaciones intraoperatorias ocurren en la LSG, cómo se pueden remediar y qué factores pueden conducir a ellas e influir en el resultado de la operación en sí. El reconocimiento y el tratamiento exitoso de las complicaciones intraoperatorias son muy importantes ya que reducen el número de reintervenciones y los costos del tratamiento.

Potential Novel RNA-Targeting Agents for Effective Lipoprotein(a) Lowering: A Systematic Assessment of the Evidence From Completed and Ongoing Developmental Clinical Trials.

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.

Potential drug-drug interactions among patients with spontaneous intracerebral hemorrhage treated at the Neurological Intensive Care Unit: a single-center experience

Abstract Our aim was to determine the prevalence of potential drug-drug interactions (pDDIs) and to identify relevant factors associated with the occurrence of the most dangerous or contraindicated pDDIs (pCDDIs) in hospitalized patients with spontaneous intracerebral hemorrhage (sICH). A retrospective cross-sectional study was performed enrolling all consecutive patients with sICH treated at the Neurological Intensive Care Unit, Clinical Center in Kragujevac, Serbia, during the three-year period (2012-2014). The inclusion criteria encompassed patients aged 18 years and over, those diagnosed with ICH, and those prescribed at least two drugs during hospitalization, while we did not include patients whose hospitalization lasted less than 7 days, those who were diagnosed with other neurological diseases and patients with incomplete medical files. For each day of hospitalization, the online checker Micromedex® software was used to identify pDDIs and classify them according to severity. A total of 110 participants were analysed. A high prevalence of pDDIs (98.2%) was observed. The median number of pDDIs regardless of severity, was 8.00 (IQR 4.75-13.00;1-30). The pairs of drugs involving cardiovascular medicines were the most commonly identified pDDIs. Twenty percent of the total number of participants was exposed to pCDDIs. The use of multiple drugs from different pharmacological-chemical subgroups and the prescribing of anticoagulant therapy significantly increase the chance of pCDDI (aOR with 95% CI 1.19 (1.05-1.35) and 7.40 (1.13-48.96), respectively). This study indicates a high prevalence of pDDIs and pCDDIs in patients with sICH. The use of anticoagulant therapy appears to be the only modifiable clinically relevant predictor of pCDDIs.

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.

Incivility among nursing faculty: A multi-country study.

BACKGROUND: In nursing programs, incivility can be a main issue affecting future registered nurses, and this may threaten patient safety. Nursing faculty play an important role in this scenario to reduce incivility. PURPOSE: The aim of this study was to assess incivility among nursing faculty in different countries. METHOD: This descriptive (cross-sectional) study was conducted to assess the extent of incivility among nursing faculty by using Incivility in Nursing Education-Revised tool and a non-probability (convenience) sampling method was used. Three hundred ninety-five nursing faculty in 10 countries distributed in four continents participated in this study. RESULTS: The results indicated that levels of incivility among participants in different countries were significantly different. Also, there was a significant difference (F = 9.313, P value = 0.000) among the nursing faculty concerning the behaviours that have been rated as disruptive. Furthermore, there was a significant difference (F = 6.392, P value = 0.000) among participants regarding uncivil behaviours that have occurred during the past 12 months. CONCLUSION: Regular assessments are needed to highlight uncivil behaviours and reduce them by making policies and rules in order to enhance academic achievement in nursing education.

Antimicrobial treatment of Erysipelatoclostridium ramosum invasive infections: a systematic review.

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.

Potential Drug-drug Interactions in Acute Ischemic Stroke Patients at the Neurological Intensive Care Unit.

BACKGROUND: Clinically relevant potential drug-drug interactions are considered preventable adverse drug reactions. OBJECTIVE: The aim of this study was to ascertain the frequency of potential drug-drug interactions in acute ischemic stroke patients and to explore factors associated with occurrence of potentially contraindicated drug-drug interactions. METHODS: This observational retrospective cohort and nested case-control study was carried out among patients treated for acute ischemic stroke at the Neurological Intensive Care Unit in the Clinical Centre Kragujevac, Serbia. The potentially drug-drug interactions for each day of hospitalization were identifi ed using Micromedex® soft ware. Based on the existence or absence of potentially contraindicated drug-drug interactions, the participants were divided into a group of cases (n=111) and the control group (n=444). RESULTS: A total of 696 patients were analysed. All patients had a minimum of one potential drug-drug interaction during hospitalization. The most common drugs involved in potential drug-drug interactions were aspirin (8.02%), diclofenac (7.49%) and warfarin (7.14%). The number of medications prescribed for simultaneous use during hospitalisation and the use of antipsychotics in therapy signifi cantly increased the likelihood of potentially contraindicated drug-drug interactions aft er adjustment by means of logistic regression for 1.2 and 3 times, respectively. CONCLUSIONS: This study suggests that patients with acute ischemic stroke are frequently exposed to potential drug-drug interactions. It is essential to identify potentially drug-drug interactions in these patients as early as possible in order to prevent adverse drug reactions and ensure safe recovery. Besides, full attention should be paid when adding each new medication in therapy, particularly when a neurologist decides to prescribe antipsychotics, such as risperidone.

Clinical significance of Cyclin D1, FGF3 and p21 protein expression in laryngeal squamous cell carcinoma.

PURPOSE: Laryngeal squamous cell carcinoma (LSCC) represents one of the most common cancers of the head and neck and the search for molecular markers is required for early diagnosis, prognosis and optimal therapy. The purpose of this study was to investigate the clinical significance of Cyclin D1, FGF3, p16 and p21 protein expression in LSCC and laryngeal dysplasia (LD) and to evaluate the associations between their expression levels and clinicopathological parameters of patients with LSCC. METHODS: Immunohistochemistry was employed to detect and quantify the expression levels of Cyclin D1, FGF3, p16 and p21 in the laryngeal tissues of 48 LSCC patients, 32 patients with LD and 28 subjects with healthy laryngeal mucosa (HLM). RESULTS: Significantly higher percentage of LSCC patients had positive Cyclin D1 expression compared with LD patients and HLM subjects (both p<0.01) and positive FGF3 expression than HLM subjects (p<0.05), while no differences in p16 and p21 positive expression were found among studied groups. The levels of Cyclin D1, FGF3 and p16 expression, as evaluated by immunostaining score, were significantly higher in patients with LSCC compared with LD and HLM groups (all p<0.05). Cyclin D1 proved to be highly sensitive and specific marker in differentiating LSCC from LD (sensitivity 81.2%, specificity 83.9%), while high sensitivity (81.2%) and lower specificity (41.4%) was observed in differentiating from HLM. Cyclin D1 and p21 expression levels were associated with regional lymph node metastases (both p<0.05) and Cyclin D1 expression levels significantly correlated with LSCC lymphatic invasion (x(2)=8.862; df=3; ?=0.031). CONCLUSIONS: Cyclin D1, FGF3 and p16 are overexpressed in patients with LSCC. Cyclin D1 is a highly sensitive marker in differentiating LSCC from LD or HLM. Cyclin D1 and p21 expression levels may be useful as predictive markers of metastases in LSCC.

[Delayed angioedema during therapy with angiotensin-converting enzyme inhibitors].

INTRODUCTION: Angiotensin-converting enzyme inhibitors are leading cause of drug-induced angioedema, with incidence of 0.1 to 0.2%. The angioedema is not of immune nature; in predisposed individuals it is caused by accumulation of vasoactive mediators due to reduced activity of angiotensin-converting enzyme. CASE REPORT: We presented a 63-year old male patient suffering from hypertension and chronic obstructive pulmonary disease, who had developed two episodes of angioedema during a 5-year long therapy with enalapril. The first episode happened after three, and the second after five years of the therapy. On both occasions, the patient was admitted to the hospital and tracheotomy was avoided in the last moment. CONCLUSION: Long-term therapy with angiotensin-converting enzyme inhibitors could be associated with delayed angioedema, especially in patients with inflammation of airways caused by infection or chronic irritation.

Knowledge of the pharmacological profile of a patient improves the quality of prescribing, the outcomes of treatment, and the utilization of health services in primary health care.

PURPOSE: To evaluate the influence of the pharmacological profile of a patient (PPP) on quality of drug prescribing, treatment effectiveness, safety, and health services utilization in a group of outpatients. METHODS: The study was designed as an open, nonrandomized trial of an intervention in health care. The outpatient intervention group (n = 39) received the PPP, and the control group (n = 36) did not. In all cases, the outcomes were observed for a 2-year period in total; in the intervention group 1 year of observation was allocated before and another year after the introduction of the PPP. RESULTS: The PPPs reduced multiple prescriptions by 1.08 ± 1.13 drugs per patient, whereas in those who did not receive the PPP, an increase of 1.44 ± 1.48 drugs per patient occurred (P < 0.001, 95% CI 1.91-3.13). A decrease in the medication appropriateness index score of 0.81 ± 0.51 per drug per patient in the intervention group was observed (P = 0.001, 95% CI 0.63-0.93), and in the control group an increase was noted (0.13 ± 0.40; P = 0.063). The majority of patients with PPP experienced fewer adverse drug reactions (0.96 ± 0.58 fewer, P < 0.001 vs. controls, 95% CI 1.39-2.13), and they were more likely to have an improvement in health status (OR 22.0, 95% CI 5.87-82.41). Finally, the PPPs decreased both the number of examinations and the number of diagnostic investigations, on average by 2.15 and 2.26 services per patient, respectively. CONCLUSIONS: Use of a pharmacological profile of a patient in primary care practice could improve not only prescribing behavior of general practitioners, but also effectiveness and safety of therapy, while reducing utilization of health services.