Drug-drug interactions in hospitalized urological patients: a retrospective cohort study.

INTRODUCTION: Exposure to potential drug-drug interactions (pDDIs) can be a notable source of avoidable drug-related harm that requires adequate management to prevent medical errors. We aimed to evaluate pDDIs and associated factors in hospitalized urological patients on admission, during hospitalization, and on discharge. METHODS: A retrospective cohort study was conducted at the Clinic of Urology of the University Clinical Centre Kragujevac, Serbia. To detect pDDIs we used Lexicomp, which categorizes pDDIs as follows: X (Avoid combination), D (Consider therapy modification), C (Monitor therapy), B (No action needed) and A (No known interaction). Multiple linear regression analysis was used to identify factors associated with the number of pDDIs. RESULTS: More than half of the 220 included patients had at least one pDDI on admission and discharge (57.3% and 63.6%, respectively), whereas 95.0% had at least one pDDI during hospitalization. The total number and number of X, D, C, and B categories of pDDIs were the highest during hospitalization and the lowest on admission. Duration of hospitalization, arrhythmias, dementia, renal failure, cancer, surgery during hospitalization, number of prescribed drugs, and various pharmacological drug classes were risk factors for a higher number of pDDIs, while age, ischemic heart disease, hypertension, and development of infection during hospitalization were protective factors in at least one of the stages. The impact of renal colic depended on the stage and category of pDDI. CONCLUSION: More than half of the urological patients were exposed to at least one pDDIs at all stages. Medical professionals should regularly screen for pDDIs, particularly in patients with risk factors.

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.

Tooth loss and periodontal status in patients with cardiovascular disease in the Serbian population: A randomized prospective study.

OBJECTIVES: Chronic periodontal infections may predispose to cardiovascular disease. Since tooth loss may be due to periodontitis it is assumed that tooth loss can also predisposes cardiovascular disease. The aim was to investigate the possible relationship between the severity of the clinical picture of periodontitis and the occurrence of cardiovascular disease. METHODS: We evaluated the association between clinical periodontal parameters, tooth loss and cardiovascular incident. A total of 100 subjects (50 subjects diagnosed with cardiovascular disease and 50 in control group without cardiovascular disease) underwent a dental examination. Tooth loss in all participants was caused only as a consequence of periodontitis. In addition to periodontal status, conventional risk factors for cardiovascular diseases (hypertension, smoking, obesity, hypercholesterolemia, diabetes) were measured, too. RESULTS: Periodontal status was worse in patients in the group with cardiovascular disease compared to the group without cardiovascular disease. A significant association was observed between tooth loss levels and cardiovascular disease. In the group of patients who had cardiovascular disease, tooth loss was more than 50%. In the group of patients without cardiovascular disease, tooth loss was about 20% of the total number of teeth. A significant association was observed between tooth loss levels and cardiovascular disease prevalence. CONCLUSION: This study presents relationship between number of teeth and cardiovascular disease, indicating a link between oral health and cardiovascular disease.

Acute Hydroxychloroquine Overdose: A Review of Published Pediatric Cases With Confirmed Hydroxychloroquine Exposure.

OBJECTIVES: This review aimed to explore and summarize information from available cases of pediatric acute hydroxychloroquine overdose with confirmed hydroxychloroquine exposure to give the clinicians a helpful perspective for its better recognition and management. METHODS: Electronic searches were conducted in PubMed/MEDLINE, Web of Science, Scopus, EBSCO and Serbian Citation Index. The abstracts from 2 toxicology conferences were manually checked for additional relevant publications, as well as reference lists of the retrieved publications. Descriptive statistics, narrative summation, and tabulation of the extracted data were made. RESULTS: Nine publications and a total of 9 patients were included in the review. Reported age of the patients varied from 2.5 to 16 years (median, 16 years). There were more female patients (77.8%). Estimated total ingested hydroxychloroquine dose was reported in 7 cases (77.8%), and it ranged from 4.0 to 20.0 g (median: 12.0 g). Four patients (44.4%) ingested hydroxychloroquine with a coingestant. Altered mental status (100.0%), cardiotoxicity (88.9%), hypotension (77.8%), and hypokalemia (55.6%) were the most commonly reported clinical manifestations. The majority of the patients were hospitalized (88.9%). More than half of the patients (55.6%) were reported to be treated in the intensive care unit. Most frequently reported therapeutic measures were the following: administration of intravenous fluids/infusions (77.8%), vasopressors (77.8%), bicarbonate therapy-sodium bicarbonate (66.7%), potassium replacement (55.6%), and intubation/ventilation (55.6%). Three patients (33.3%) died. CONCLUSIONS: Management of acute hydroxychloroquine overdose in children should be symptomatic and tailored to observed clinical manifestations. There is a need for additional investigations to better understand the impact and effectiveness of various treatment options.

Delirium associated with the use of macrolide antibiotics: a review.

OBJECTIVE: This review aimed to explore and summarise available cases of delirium suspected to be associated with the use of macrolide antibiotics reported in the literature and the United States Food and Drug Administration's Adverse Event Reporting System (FAERS) database. METHODS: Electronic searches of the literature were conducted in four online databases: PubMed/MEDLINE, Scopus, Web of Science and Serbian Citation Index (SCIndeks). A search of FAERS database was also conducted to supplement the findings of the literature search. Descriptive statistics, narrative summation and tabulation of the extracted data were made. RESULTS: Cases of delirium which satisfied inclusion criteria were found for clarithromycin, azithromycin, erythromycin and telithromycin. Delirium was described in patients of various age groups, including children. Drug-drug interactions may have contributed to its occurrence in some of the cases. Average time to onset of delirium was 2.5 days for azithromycin and 3.3 days for clarithromycin. CONCLUSIONS: Considering that these drugs may be a possible cause of delirium, clinicians should be aware that timely recognition of this possible side effect can lead to earlier discontinuation of the culprit drug, reduce time spent in a delirious state and improve patients' outcomes.KEY POINTSCases of delirium which satisfied inclusion criteria were found for clarithromycin, azithromycin, erythromycin and telithromycin.Cases of delirium were described in patients of various age groups, including children.Drug-drug interactions may have contributed to the occurrence of delirium in some of the cases.Time to onset of delirium ranged from 2 to 3.5 days (mean: 2.5 days) for azithromycin and from 1 to 7 days (mean: 3.3 days) for clarithromycin.Cessation of the macrolide antibiotic seems to be the best management strategy, although some of the patients may, in addition, require antipsychotics.

Effect of the local probiotics in the therapy of periodontitis A randomized prospective study.

OBJECTIVES: The use of local probiotics in the therapy of periodontitis is reflected in their ability to antagonize periodontopathogens and modulates the immune response of the host to the presence of pathogenic microorganisms. The aim of this study was to investigate the use of local probiotics in the treatment of periodontitis as an adjunctive therapy to scaling and root planning (SRP). METHODS: The study involved 80 patients diagnosed with periodontitis. All participants underwent SRP therapy. Semi-solid probiotic was then locally applied to the periodontal pocket in randomly selected patients for the test group (40 of them). The other 40 patients were in the control group. Clinical parameters including periodontal pocket depth (PPD), bleeding on probing (BOP) and plaque index (PI) were measured at baseline, and at 7 and 30 days after treatment. RESULTS: Seven days after the applied therapy in the test and control group, there was a significant decrease in the values or BOP (p < .001), while the values of other parameters did not show a statistically significant difference (p < .05). One month after the therapy in both groups, there was a statistically significant difference in the values of all clinical parameters (p < .001). CONCLUSIONS: Based on the results of this pilot study, it can be said that, during periodontal treatment, topical application of probiotics in combination with SRP increases the effectiveness of conventional non-surgical therapy of periodontitis.

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.

Bleeding Index and Monocyte Chemoattractant Protein 1 as Gingival Inflammation Parameters after Chemical-Mechanical Retraction Procedure.

OBJECTIVE: A widely used chemical-mechanical method of gingival retraction can cause gingival tissue damage. The aim of this study was to test the influence of the chemical-mechanical gingival retraction procedures on the gingival bleeding index (GBI) and the salivary concentration of monocyte chemoattractant protein 1 (MCP-1) as an indicator of inflammatory changes in the gingiva. MATERIALS AND METHODS: The effects of 2 different retraction agents (aluminum chloride and ferric sulfate) were compared, particularly their tissue damaging effect during tooth preparation. Therefore, GBI values and the salivary concentration of MCP-1 were assessed during the chemical-mechanical method of gingival retraction in a homogenous group of respondents. The subjects (n = 60) were divided into 2 experimental groups (G1 and G2) regarding the need for tooth preparing and making artificial crowns. Each group was further divided into 2 subgroups (R1 and R2) according to the type of the gingival retraction agent used (aluminum chloride and ferric sulfate). RESULTS: Compared to the values at the study start, a statistically significant increase in GBI and salivary MCP-1 (p < 0.001) 1 day after gingival retraction agent application was observed in both experimental groups. After 72 h, the values were lower than in the second observation period but still statistically significantly higher compared to the study start (p < 0.001), which indicated the reversibility of the tissue changes. CONCLUSION: Higher values of the investigated parameters were observed in the group of subjects with prepared teeth, and clinical changes were more pronounced after the use of ferric sulfate.

Determination of Salivary Myeloperoxidase, Immunoglobulin E, and Tumor Necrosis Factor-α after Complete Denture Insertion.

OBJECTIVE: To detect activities of salivary myeloperoxidase (MPO) and concentrations of salivary tumor necrosis factor (TNF)-α as indicators of inflammatory reaction and salivary immunoglobulin E as an indicator of allergic reaction after complete insertion of acrylic dentures. SUBJECTS AND METHODS: Complete dentures were made for a uniform group of elderly patients, and saliva samples were taken immediately before they were given to the patients, as well as 2, 3, 7, and 30 days after insertion of the dentures, with simultaneous monitoring of changes in the oral mucosa. RESULTS: After 7 and 30 days of wearing upper and lower complete dentures, nonsignificant increases in salivary MPO and TNF-α were proven to be indicators of inflammation. No changes were observed in the values of salivary immunoglobulin E during a 30-day observational period, which excluded the appearance of allergic reactions to acrylic materials in the tested group of patients. CONCLUSION: A nonsignificant increase in the levels of MPO was observed on day 7; it decreased after 30 days. TNF-α also tended to increase in a nonsignificant manner.

Effect of periodontal treatment in renal transplant recipients.

OBJECTIVE: To evaluate the effect of periodontal treatment on gingival overgrowth in a group of renal transplant patients. SUBJECTS AND METHODS: Twenty-five renal transplant recipients receiving immunosuppressive therapy with cyclosporine A (CsA) were randomly assigned to 2 groups. Group 1 (n = 15) included patients who had been specifically referred to a dental clinic to prevent gingival overgrowth and were given full periodontal therapy. Group 2 (n = 10) was comprised of patients who did not receive any professional periodontal cleaning. Patients from both groups were examined to determine their periodontal status before and after 3, 6 and 12 months in terms of their plaque index, gingival index and gingival overgrowth. During the examination, their overall health was stable. RESULTS: For group 1, the scores were 1.89 (baseline), 0.98 (6 months) and 0.56 (12 months), and hence there were significant reductions (p = 0.0001). The gingival indices were 1.71 (baseline), 0.76 (6 months) and 0.35 (12 months), and the reductions were also significant (p = 0.0001). A significant association was observed between poor oral hygiene and the degree of gingival overgrowth. The 1-year post-treatment follow-up showed that patients in group 1 did not develop gingival overgrowth due to the use of CsA as group 2 did without prior periodontal therapy. CONCLUSION: Oral hygiene status was the most important variable related to the development and degree of gingival overgrowth due to the use of CsA.

Evaluation of medicinal interventions for the management of oral submucous fibrosis: a systematic review of the literature.

Oral submucous fibrosis is a chronic, progressive scarring disease associated with both significant morbidity including pain and limited mouth opening and an increased risk for malignancy. This systematic review evaluated the different medicinal (i.e. nonsurgical) interventions available for the management of oral submucous fibrosis. An automated literature searches of online databases from January 1960 to December 2013 were performed and only studies with high level of evidence based on the guidelines of the Oxford Centre for evidence-based medicine were selected. Thirteen studies (3 randomized controlled trials and 10 clinical trials/controlled clinical trials) were included and drugs like steroids, hyaluronidase, human placenta extracts, chymotrypsin and collagenase, pentoxifylline, nylidrin hydrochloride, iron and multivitamin supplements including lycopene were used. There is a clear lack of evidence on the available drug treatment for oral submucous fibrosis and further high quality randomized controlled trials are needed to evaluate the different therapeutic agents.

Priapism associated with anti-seizure medications: a pharmacovigilance study and a review of published cases.

BACKGROUND: Recently, case reports of priapism associated with the use of some anti-seizure medications began to emerge in the literature. We aimed to investigate if there is a potential safety signal of priapism among individual anti-seizure medications and to search the literature for relevant published cases. RESEARCH DESIGN AND METHODS: We conducted a disproportionality analysis using OpenVigil 2.1 to query the United States Food and Drug Administration's Adverse Event Reporting System (FAERS) database. Literature search was conducted in PubMed/MEDLINE, Scopus and Web of Science up to 12 July 2023. RESULTS: We identified positive signal of priapism for valproic acid and its derivatives (n = 23, chi-squared = 59.943, PRR = 4.566), gabapentin (n = 20, chi-squared = 9.790, PRR = 2.060), lamotrigine (n = 16, chi-squared = 8.318, PRR = 2.120), levetiracetam (n = 16, chi-squared = 10.766, PRR = 2.329), topiramate (n = 14, chi-squared = 28.067, PRR = 3.972) and carbamazepine (n = 8, chi-squared = 6.147, PRR = 2.568), as well as published cases of priapism associated with these drugs. We also found published cases of priapism for pregabalin and phenytoin in the literature and FAERS, and at least one reported adverse event of priapism in FAERS for clonazepam, lacosamide, ethosuximide, oxcarbazepine, and vigabatrin in which they were considered primary suspect. CONCLUSIONS: Our study identified signals for priapism for several anti-seizure medications, but these results need to be confirmed in well-designed pharmacoepidemiological studies.

Vitamin C Levels in Pregnant Women and the Efficacy of Vitamin C Supplements in Preventing Premature Rupture of Membranes: A Systematic Review and Meta-Analysis

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.

Factors associated with potentially inappropriate prescribing in elderly patients with various degrees of chronic kidney disease.

INTRODUCTION: This study aimed to compare the prevalence of potentially inappropriately prescribed drugs in hemodialysis patients and patients with chronic kidney disease who did not require renal replacement therapy, as well as to identify risk factors associated with potentially inappropriate prescribing. METHODS: The study was designed as a cross-sectional study conducted at the Department of Nephrology, Clinical Center in Nis, Serbia. The patients were divided into two groups: (1) patients on hemodialysis treatment and (2) patients with various degrees of chronic kidney disease without renal replacement therapy. The presence or absence of potentially inappropriate prescribing was determined using the 2015 AGS Beers criteria. FINDINGS: The study included a total of 218 patients aged 65 years and over. The number of patients with potentially inappropriate prescribed drugs did not differ significantly (chi-square = 0.000, p = 1.000) between patients on hemodialysis (27 of 83, i.e., 32.5%) and patients with various degrees of chronic kidney disease without renal replacement therapy (44 of 135, i.e., 32.6%). Factors associated with potentially inappropriate prescribing in hemodialysis patients were the number of drugs (hazard ratio [HR] = 1.919, 95% confidence interval [CI]: 1.325-2.780) and number of comorbidities (HR = 1.743, 95% CI: 1.109-2.740). The number of drugs (HR = 1.438, 95% CI: 1.191-1.736) was the only independent factor associated with increased risk of potentially inappropriate prescribing in patients without renal replacement therapy. DISCUSSION: Our study showed that potentially inappropriate prescribing is a relatively frequent phenomenon present in about a third of patients in both study groups. The number of prescribed drugs was the main factor associated with the increased risk of potentially inappropriate prescribing in both groups.

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.

Mirtazapine-induced Acute Pancreatitis in Patients With Depression: A Systematic Review.

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.

Factors associated with gastrointestinal dysmotility in critically ill patients.

Critical illness may disrupt nutritional, protective, immune, and endocrine functions of the gastrointestinal tract, leading to a state of gastrointestinal dysmotility. We aimed to identify factors associated with the occurrence of gastrointestinal dysmotility in critically ill patients. A cross-sectional retrospective study was conducted, using patient files as a source of data. The study included 185 critically ill patients treated in the intensive care unit of the University Clinical Center, Kragujevac, Serbia, from January 1, 2016, to January 1, 2022. Significant risk factors associated with some form of gastrointestinal dysmotility were acute kidney injury (with paralytic ileus, nausea, vomiting, and constipation), recent abdominal surgery (with ileus, nausea, vomiting, and constipation), mechanical ventilation (with ileus, and nausea), age (with ileus and constipation), and use of certain medication such as opioids (with ileus, gastro-esophageal reflux, nausea, vomiting, and constipation), antidepressants (with ileus, nausea, and vomiting), and antidiabetics (with ileus). On the other hand, Charlson comorbidity index had divergent effects, depending on the form of gastrointestinal dysmotility: it increased the risk of gastro-esophageal reflux but protected against ileus, nausea, and vomiting. In clonclusion, recognition of factors associated with gastrointestinal dysmotility should initiate preventative measures and, thus, accelerate the recovery of critically ill.

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.

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.

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.