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Background: Ciprofol was approved for use in intensive care unit (ICU) patients requiring sedation during mechanical ventilation in July 2022. A pooled post-hoc analysis of phase 2 and phase 3 trials was conducted primarily to explore hypotension-free outcome in ICU patients who required mechanical ventilation and achieved the target light sedation goal at an early stage after being sedated with ciprofol or propofol. Methods: All eligible ICU patients who were expected to require sedation for 6–24 h were randomly assigned in a 2:1 ratio to either a ciprofol or propofol group. Ciprofol or propofol was initially infused at loading doses of 0.5 or 1.0 mg/kg followed by maintenance doses of 0.3 or 1.5 mg/kg/h. Ciprofol or propofol dosages were adjusted up or down at rates of 0.05–0.10 mg/kg/h or 0.25–0.50 mg/kg/h, respectively, to achieve the target light sedation (a Richmond Agitation-Sedation Scale of -2 to + 1). The primary post-hoc outcome was the hypotension-free rate in patients who had achieved the target sedation goal after 30-min administration of ciprofol or propofol. Results: In total, 174 patients were enrolled for pooled post-hoc analysis, of whom 116 and 58 were assigned to the ciprofol and propofol groups, respectively. The hypotension-free rate was significantly higher in patients who achieved the target sedation goal after 30-min administration of ciprofol (93.0% vs. 81.0%, P = 0.018), and especially in the subgroups of males and patients aged < 65 years. Multivariable analysis revealed that ciprofol treatment, a younger age and lower baseline body mass index were independent favorable predictors for a higher hypotension-free rate in patients who achieved the target sedation goal after 30-min of drug administration. Moreover, hypotension-free patients who reached the target sedation level after 30 min had a more favorable short-term prognosis including a lower incidence of drug-related treatment-emergent adverse events, shorter time to extubation and fewer dose adjustments of ciprofol or propofol (all P < 0.05). Conclusion: ICU patients undergoing mechanical ventilation and sedated with ciprofol had significantly lower rate of hypotension during the early phase of achieving light sedation during a 6–24 h period, leading to a more favorable short-term prognosis (within 24 h). Trial registration: Phase 2 trial (clinicaltrials.gov, NCT04147416. Registered November 1, 2019, https://classic.clinicaltrials.gov/ct2/show/NCT04147416) and phase 3 trial (clinicaltrials.gov, NCT04620031. Registered November 6, 2020, https://classic.clinicaltrials.gov/ct2/show/NCT04620031). [ABSTRACT FROM AUTHOR]

Background: Opioid-reduced multimodal analgesia has been used clinically for many years to decrease the perioperative complications associated with opioid drugs. We aimed to assess the clinical effects of opioid-reduced anesthesia during thoracoscopic sympathectomy. Methods: Surgical patients (n = 151) with palmar hyperhidrosis were randomly divided into control (Group C, 73 patients) and test (Group T, 78 patients) groups. All patients were administered general anesthesia using a laryngeal mask. In Group C, patients received propofol, fentanyl, and cisatracurium for anesthesia induction, and maintenance was achieved with propofol and remifentanil, along with mechanical ventilation during the operation. In Group T, anesthesia was induced with propofol, dezocine, and dexmedetomidine (DEX) and maintained with propofol, DEX, and an intercostal nerve block, along with spontaneous breathing throughout the operation. Perioperative complications related to opioid use include hypotension, bradycardia, hypertension, tachycardia, hypoxemia, nausea, vomiting, urine retention, itching, and dizziness were observed. To assess the impact of these complications, we recorded and compared vital signs, blood gas indices, visual analogue scale (VAS) scores, adverse events, and patient satisfaction between the two groups. Results: Perioperative complications related to opioid use were similar between groups. There were no significant differences in the type of perioperative sedation, analgesia index, respiratory and circulatory indicators, blood gas analysis, postoperative VAS scores, adverse reactions, propofol dosage, postoperative recovery time, and patient satisfaction. Conclusions: In minimally invasive surgeries such as thoracoscopic sympathectomy, opioid-reduced anesthesia was found to be safe and effective; however, this method did not demonstrate clinical advantages. Trial registration: Chinese Clinical Trial Register: ChiCTR2100055005, on December 30, 2021. [ABSTRACT FROM AUTHOR]

In this retrospective cohort study, we compared neonatal and maternal outcomes after exposure of different psychopharmacological classes of drugs. Both psychiatric diseases and pharmacological treatment of these are associated with lower birth weights, lower APGAR scores, and NICU admission. Therefore, we tried to rule out the role of psychotropics as if no differences were found between pharmacological classes, the lower birthweights might not be attributable to these. We divided our groups in exposed to atypical antipsychotic drugs, Selective Serotonin Reuptake Inhibitors (SSRI), Tricyclic Antidepressants (TCA), benzodiazepines, and different combinations of psychotropic drugs. The last group included SSRIs combined with benzodiazepines, methylphenidate, lithium, and classic antipsychotic drugs. We used univariate regression analysis to see which factors from our rich dataset including pharmacological class, are associated with birth weight, APGAR scores, gestational age, and NICU admission. The significant associations from univariate analyses were further analyzed using ancova analysis or logistic regression where applicable. We found no clinically relevant differences in neonatal and maternal outcomes between the different exposed pharmacological classes. However, our dataset may have been too small to draw firm conclusions. [ABSTRACT FROM AUTHOR]

Simple Summary: This nationwide cohort study evaluated the incidence and severity of immune-related adverse events (irAEs) in melanoma patients receiving adjuvant versus advanced anti-PD-1 therapy. A total of 1465 advanced melanoma patients and 908 adjuvant-treated patients were included. Patients in the adjuvant group were younger, had superior ECOG performance status, and had fewer comorbidities compared to those in the advanced group. No significant difference was observed in the incidence of grade III-IV irAEs between the two groups. However, higher ECOG status (>1) and the presence of any comorbidities were independently associated with an increased risk of irAE development across both treatment settings. Although adjuvant therapy was not linked to a heightened risk of severe irAEs compared to advanced therapy, it was more frequently discontinued due to toxicity in the adjuvant group. These findings provide critical insights for informing patient consultations regarding adjuvant anti-PD-1 treatment. Introduction: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups. Methods: This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development. Results: A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group (p < 0.01), and had a better ECOG performance status (p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% (p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02–1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20–3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74–1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% (p < 0.01). Conclusions: Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in adjuvant and advanced treated melanoma patients. Patients treated in the adjuvant setting did not have an increased risk of developing severe irAEs compared to advanced melanoma patients. These findings are of clinical significance in consulting patients for adjuvant anti-PD-1 treatment. [ABSTRACT FROM AUTHOR]

Background: Oral potassium binders have a role in the management of acute hyperkalemia among hospitalized patients. However, with therapeutic additions to this class, there is insufficient evidence between potassium binders to support a standard of care recommendation for use in this acute setting. Objective: The purpose of this study was to compare the acute potassium lowering effects of sodium zirconium cyclosilicate (SZC) and sodium polystyrene sulfonate (SPS). Methods: A retrospective review of admitted patients who received SZC or SPS was conducted after exemption from the Institutional Review Board. Patients with baseline potassium values less than 5.1 mmol/L or factors contributing to potentially false report of serum potassium were excluded. The primary outcome was the average change in potassium from baseline to 24 hours following potassium binder administration. Secondary outcomes compared changes to potassium from baseline to various time periods after administration, presence of electrolyte changes, and documentation of serious adverse events. Results: A total of 246 patients were included, with 128 receiving SZC and 118 receiving SPS. Mean change in serum potassium (mmol/L) at 24 hours was not significant between binders (−.78 vs −.91; P =.22). Secondary efficacy and safety outcomes were also similar between groups. A total of 5 serious adverse events were reported, occurring only in the SPS group. Conclusion: SZC and SPS have comparable effects in acute potassium reduction, with serious gastrointestinal adverse events documented only in SPS patients. Health systems may consider this data in determining medication formularies or during order set development. [ABSTRACT FROM AUTHOR]

Simple Summary: Most cancer patients are older and have concomitant diseases because the incidence of most cancer types increases with age. This leads to patients taking a variety of medications that can cause drug-related problems (DRPs). DRPs can cause harm, including increased illness, avoidable hospital stays, and even death. Common DRPs are drug–drug interactions, not taking medication as prescribed, and adverse drug reactions. In our study, we aimed to assess these medication risks in hospitalized cancer patients and to identify factors that influence their health-related quality of life (HRQOL) as a patient-relevant outcome. The results of the pharmacist-led medication reviews show that DRPs are common in hospitalized cancer patients. Therefore, patient questionnaires about therapy-related symptoms could improve the detection of DRPs. While drug-related factors had no effect on HRQOL during the hospital stay, our analysis revealed other influencing factors, such as relapse status of the cancer disease and length of hospital stay. Background: We aimed to assess medication risks and determine factors influencing the health-related quality of life (HRQOL) in cancer inpatients. Methods: A retrospective analysis was conducted to identify drug-related problems (DRPs) based on medication reviews, including patient-reported outcomes (PROs). Multiple linear regression analyses were performed to identify sociodemographic, disease-related, and drug therapy-related factors influencing changes from hospital admission to discharge in the scales of the EORTC QLQ-C30 questionnaire. Results: A total of 162 inpatients with various hematological and solid cancer diseases was analyzed. Patients received a mean of 11.6 drugs and 92.6% of patients exhibited polymedication resulting in a mean of 4.0 DRPs per patient. Based on PRO data, 21.5% of DRPs were identified. Multiple linear regression models described the variance of the changes in global HRQOL and physical function in a weak-to-moderate way. While drug therapy-related factors had no influence, relapse status and duration of hospital stay were identified as significant covariates for global HRQOL and physical function, respectively. Conclusion: This analysis describes underlying DRPs in a German cancer inpatient population. PROs provided valuable information for performing medication reviews. The multiple linear regression models for global HRQOL and physical function provided explanations for changes during hospital stay. [ABSTRACT FROM AUTHOR]

Following a national multicentre study, two emergency department (ED) screening tools were developed to determine risk of medication-related problems; one for use at ED presentation and another at ED discharge to the community. This study aimed to determine the inter-rater reliability amongst ED health professionals when applying these screening tools to a series of case scenarios. A prospective, cross-sectional study was undertaken in the ED of a major metropolitan hospital. Twelve case scenarios were developed following ED observation of a range of patients, which were incorporated into a questionnaire and distributed to 50 health professionals. Inter-rater reliabilities of each explanatory variable of the screening tools and overall assessment were calculated using Fleiss' multi-rater kappa. The questionnaire was completed by 15 doctors, 19 nurses and 16 pharmacists. Fleiss' kappa showed an overall inter-rater reliability for the ED presentation tool of 0.83 (95% CI 0.83–0.84), indicating near perfect agreement. Fleiss' kappa for the ED discharge tool was 0.83 (95% CI 0.83–0.85), which also showed near perfect agreement. The screening tools produced favourable inter-rater reliability amongst ED health professionals. These results have important implications for ensuring consistency of ED decision-making in screening patients at risk of developing medication-related problems. [ABSTRACT FROM AUTHOR]

Background: Propofol is effective and used as a kind of routine anesthetics in procedure sedative anesthesia (PSA) for ureteroscopy. However, respiratory depression and unconscious physical activity always occur during propofol-based PSA, especially in elderly patients. Esketamine has sedative and analgesic effects but without risk of cardiorespiratory depression. The purpose of this study is to investigate whether esketamine can reduce the propofol median effective dose (ED50) for successful ureteroscope insertion in elderly male patients. Materials and methods: 49 elderly male patients undergoing elective rigid ureteroscopy were randomly divided into two groups: SK Group (0.25 mg/kg esketamine+propofol) and SF Group (0.1 µg/kg sufentanil+propofol). Patients in both two groups received propofol with initial bolus dose of 1.5 mg/kg after sufentanil or esketamine was administered intravenously. The effective dose of propofol was assessed by a modified Dixon's up-and-down method and then was adjusted with 0.1 mg/kg according to the previous patient response. Patients' response to ureteroscope insertion was classified as "movement" or "no movement". The primary outcome was the ED50 of propofol for successful ureteroscope insertion with esketamine or sufentanil. The secondary outcomes were the induction time, adverse events such as hemodynamic changes, hypoxemia and body movement were also measured. Result: 49 patients were enrolled and completed this study. The ED50 of propofol for successful ureteroscope insertion in SK Group was 1.356 ± 0.11 mg/kg, which was decreased compared with that in SF Group, 1.442 ± 0.08 mg/kg (P = 0.003). The induction time in SK Group was significantly shorter than in SF Group (P = 0.001). In SK Group, more stable hemodynamic variables were observed than in SF Group. The incidence of AEs between the two groups was not significantly different. Conclusion: The ED50 of propofol with esketamine administration for ureteroscope insertion in elderly male patients is 1.356 ± 0.11 mg/kg, significantly decreased in comparsion with sufentanil. Trial registration: Chinese Clinical Trial Registry, No: ChiCTR2300077170. Registered on 1 November 2023. Prospective registration. http://www.chictr.org.cn. [ABSTRACT FROM AUTHOR]

Background: Critically ill pediatric patients face an increased risk of venous thromboembolism, and enoxaparin is commonly used for prophylaxis and treatment. However, optimal dosing in this population remains uncertain, and individualized dose optimization is seen as a promising approach. This systematic review aims to refine dosing strategies in critically ill pediatric patients, with the goal of improving outcomes and reducing VTE and bleeding complications. Methods: The study followed PRISMA guidelines and employed a comprehensive search strategy using relevant MeSH terms and keywords. Data extraction and management were performed using standardized protocols. The quality of the included studies was assessed using appropriate tools. The statistical analysis was performed using R software (Version 4.3.0, Vienna, Austria) and RStudio interface (Version 2023.03.0, Boston, MA, USA). Results: The systematic review included 15 studies on individualized dosing strategies of enoxaparin in critically ill pediatric patients. The studies revealed variations in dosing strategies, including higher initial doses for neonates and infants. The administration route (IV or SC) and dosing frequency were also explored, with some studies suggesting IV administration as an alternative to SC. Clinical outcomes such as time to therapeutic anti-Xa levels, bleeding events, side effects, and the development of venous thromboembolism were assessed. Anti-Xa level-directed dosing and weight-based dosing were found to yield optimal outcomes. Meta-analysis results showed low mortality rates, a low incidence of thrombotic events with therapeutic prophylactic doses, and a low frequency of bleeding events. Conclusion: This systematic review concluded that initial high dose of enoxaparin is required to achieve therapeutic levels. However, limited data regarding dose optimization of enoxaparin is available on critically ill pediatrics. Pharmacokinetic studies, therapeutic drug monitoring, and population pharmacokinetic modelling can guide personalized dosing decisions. The implementation of personalized dosing protocols in clinical practice has the potential to improve patient care, enhance safety, and optimize anticoagulation management in critically ill pediatrics. Further research including prospective studies and RCTs is essential to establish pediatric-specific dosing guidelines and target anti-factor Xa ranges for enoxaparin in critically ill pediatrics. [ABSTRACT FROM AUTHOR]

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Purpose: There is no consensus in the current literature on the analgesic role of duloxetine after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Thus, we designed this meta-analysis to reveal the analgesic effectiveness and safety of duloxetine in TKA or THA. Methods: As of October 2022, two authors (L.C. and W.Q.J.) independently searched five main databases (EMBASE, Web of Science, PubMed, Cochrane Library, and Google Scholar) to find relevant studies. Duloxetine vs. placebo in randomized controlled trials (RCTs) for THA or TKA were included. We set perioperative total opioid consumption as the primary outcome. Secondary outcomes included resting or dynamic pain scores over time, gastrointestinal adverse events, neurological adverse events, and other adverse reactions. Results: Eight RCTs with 695 patients were incorporated in our study. This meta-analysis showed high evidence that duloxetine was effective in reducing perioperative opioid consumption (Standard mean difference [SMD] = − 0.50, 95% confidence intervals [CI]: −0.70 to − 0.31, P < 0.00001) and low to moderate evidence that duloxetine could reduce pain within three weeks after surgery. Low to high evidence showed no differences between the two groups for most adverse events. Substantial evidence suggests that duloxetine can reduce nausea and vomiting after surgery (Risk ratio [RR] = 0.69, 95% CI: 0.50 to 0.95, P = 0.02, I2 = 4%). However, moderate evidence suggested that duloxetine might be associated with increased postoperative drowsiness (RR = 1.83, 95% CI: 1.08 to 3.09, P = 0.02, I2 = 0%). Conclusion: Duloxetine reduced overall opioid consumption in the perioperative period and relieved pain within three weeks after surgery without increasing the risk of adverse drug events. Duloxetine can be part of a multimodal management regimen in patients with THA and TKA. [ABSTRACT FROM AUTHOR]

Background: Suboptimal prescribing, including the prescription of potentially inappropriate medications (PIM), is frequent in patients aged 65 years and older. PIMs are associated with adverse drug events, which may lead to hospital admissions and readmissions for the most serious cases. Several tools, known as lists of PIMs, can detect suboptimal prescription. Objective: This systematic review aimed to identify which lists of PIMs are associated with hospital readmission of older patients. Patients and Methods: MEDLINE, the Cochrane Library, EMBASE, and clinicaltrials.gov were searched for the period from 1 January 1991 up to 12 May 2022 to identify original studies assessing the association between PIMs and hospital readmissions or emergency department (ED) revisits within 30 days of discharge in older patients. This study is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Checklist, and the risk of bias was assessed with the Newcastle–Ottawa Quality Assessment Scale for Cohort Studies (NOS) and the revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Results: A total of six studies presenting four different lists of PIMs were included. Readmission rates varied from 4.3 to 25.5% and the odds ratio (OR) between PIMs and hospital readmission varied from 0.92 [95% confidence interval (CI) 0.59; 1.42] to 6.48 [95% CI 3.00; 14.00]. Only two studies found a statistically significant association between a list of PIMs and hospital readmission. These two studies used different tools: the Screening Tool of Older Person's Prescriptions (STOPP) and the Screening Tool to Alert Doctors to Right Treatment (START) and a combination of Beers Criteria® and STOPP and START. Conclusion: This systematic review shows that the association between list of PIMs and 30-day unplanned readmissions remains unclear and seems dependent on the PIM detection tool. Further studies are needed to clarify this association. PROSPERO registration number CRD42021252107. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune-related adverse events (irAEs) are becoming an increasingly prevalent and well-studied phenomenon. Little is known about how clinical practice has evolved to incorporate our growing knowledge on the subject. We identified temporal trends in irAE management as well as factors associated with improved outcomes among these patients such as timely specialty consultation. These findings can improve the quality of management algorithms for immune-related adverse events at our institution and may inform policies in other institutions. Understanding of immune-related adverse events (irAEs) has evolved rapidly, and management guidelines are continually updated. We explored temporal changes in checkpoint inhibitor-induced irAE management at a tertiary cancer care center to identify areas for improvement. We conducted a single-center retrospective study of patients who developed a gastrointestinal, pulmonary, renal, or cardiac irAE between July and 1 October in 2019 or 2021. We collected patient demographic and clinical information up to 1 year after toxicity. Endoscopic evaluation and specialty follow-up after discharge for patients with gastrointestinal irAEs declined between the 2019 and 2021 periods. Symptom duration and steroid taper attempts also declined. For pulmonary irAEs, rates of specialty consultation, hospital admission and readmission, and mortality improved in 2021 compared with 2019. Follow-up rates after hospital discharge were consistently low (<50%) in both periods. For cardiac irAEs, consultation with a cardiologist was frequent and prompt in both periods. Outpatient treatment and earlier specialty consultation improved outcomes with gastrointestinal irAEs. Our study exploring irAE practice changes over time identified areas to improve management; specifically, timely specialty consultation was associated with better outcomes for gastrointestinal irAEs. These findings can help improve the quality of management algorithms at our institution and may inform policies in other institutions. [ABSTRACT FROM AUTHOR]

Background: The burden of lumbar degenerative diseases (LDD) has increased substantially with the unprecedented aging population. Identifying elderly patients with high risk of postoperative adverse events (AEs) and establishing individualized perioperative management is critical to mitigate added costs and optimize cost-effectiveness to the healthcare system. We aimed to develop a predictive tool for AEs in elderly patients with transforaminal lumbar interbody fusion (TLIF), utilizing multivariate logistic regression, single classification and regression tree (hereafter, "classification tree"), and random forest machine learning algorithms. Methods: This study was a retrospective review of a prospective Geriatric Lumbar Disease Database (age ≥ 65). Our outcome measure was postoperative AEs, including prolonged hospital stays, postoperative complications, readmission, and reoperation within 90 days. Patients were grouped as either having at least one adverse event (AEs group) or not (No-AEs group). Three models for predicting postoperative AEs were developed using training dataset and internal validation using testing dataset. Finally, online tool was developed to assess its validity in the clinical setting (external validation). Results: The development set included 1025 patients (mean [SD] age, 72.8 [5.6] years; 632 [61.7%] female), and the external validation set included 175 patients (73.2 [5.9] years; 97 [55.4%] female). The predictive ability of our three models was comparable, with no significant differences in AUC (0.73 vs. 0.72 vs. 0.70, respectively). The logistic regression model had a higher net benefit for clinical intervention than the other models. A nomogram based on logistic regression was developed, and the C-index of external validation for AEs was 0.69 (95% CI 0.65–0.76). Conclusion: The predictive ability of our three models was comparable. Logistic regression model had a higher net benefit for clinical intervention than the other models. Our nomogram and online tool (https://xuanwumodel.shinyapps.io/Model%5ffor%5fAEs/) could inform physicians about elderly patients with a high risk of AEs within the 90 days after TLIF surgery. [ABSTRACT FROM AUTHOR]

Background Hyponatremia is defined as sodium less then 135mEq/l. It is a clinico etiological study on hyponatremic elderly patients presenting to emergency department. Aim and objective All patients aged 60years and above with their serum sodium level less than135mEq/L were included in the study. Methods A total of 100 patients were included in the study. It is a prospective observational study conducted from 2016 to 2018 in a tertiary care hospital. Results We had more of male patients compared to female, more during there sixth and seventh decade. with a mean age of 66.63 years. more of neurological symptoms like altered sensorium, drowsiness and seizures. Majority of the patients are with mild hyponatremia (52%) followed by severe grade (25%) and 23% of them had moderate hyponatremia. And mean serum sodium 124.56mEq/. Patients with mild and moderate hyponatremia most of their presenting symptoms were non-neurological, whereas patients with severe hyponatremia majority of them presented with neurological symptoms. Hypertension followed by diabetes mellitus was the most common preexisting illness present among the patients. Among the various aetiologies reported among our study subjects the most common aetiology was found to be SIADH that is euvolemic hyponatremia was found to be common in present study. The second most common cause was drug induced Like diuretics. Conclusion As the p value >0.05 so patients had more than one factor influencing the occurrence of hyponatremia. Mortality in our study was around 4.30% which was significantly low. The mortalityis mainly due to an underlying primary disease. length of stay increased with the severity of disease. [ABSTRACT FROM AUTHOR]

Background: In a large proportion of patients admitted to the emergency department (ED), the initial main symptom is nonspecific. One possible reason for this, especially in older patients, may be adverse drug reactions (ADR) due to their frequent polypharmacy. Aim: To illustrate the incidence of ADRs, the affected patient population including risk factors, and drug classes with ADRs leading to nonspecific symptoms. To provide practice recommendations for the management of ADRs in the ED. Material and methods: Presentation of the pharmacological principles on ADRs, statistics of pharmacovigilance centers as well as original literature including experiences from clinical practice and own projects. Results: In 10% of patients with nonspecific symptoms an ADR is responsible for presentation in the ED. In 60% of cases these ADRs are not correctly identified in the ED setting. A small number of drug classes are responsible for most of these referrals. Databases, risk stratification, clinical pharmacists, or clinical decision support systems are available to improve ADR identification and management. As these options are partly associated with considerable costs or the validation for German EDs is missing, a widespread application does not take place. Conclusion: Correct identification of ADRs in patients with nonspecific symptoms in the ED is necessary to initiate adequate treatment. These ADRs are often overlooked because processes and tools for identification and management are not applied in the ED, leading to a lack of awareness. For high-risk patients in the ED, the focus should be on drug history, ideally considering patient-specific risk factors and specific drug classes. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the relationship between medication regimen complexity-intensive care unit (MRC-ICU) score at 24 hours and medication errors identified throughout the ICU. Methods: A single-center, observational study was conducted from August to October 2021. The primary outcome was the association between MRC-ICU at 24 hours and total medication errors identified. During the prospective component, ICU pharmacists recorded medication errors identified over an 8-week period. During the retrospective component, the electronic medical record was reviewed to collect patient demographics, outcomes, and MRC-ICU score at 24 hours. The primary outcome of the relationship of MRC-ICU at 24 hours to medication errors was assessed using Pearson correlation. Results: A total of 150 patients were included. There were 2 pharmacists who recorded 634 errors during the 8-week study period. No significant relationship between MRC-ICU and medication errors was observed (r 2 =.13, P =.11). Exploratory analyses of MRC-ICU relationship to major interventions and harm scores showed that MRC-ICU scores >10 had more major interventions (27 vs 14, P =.27) and higher harm scores (15 vs 7, P =.33), although these values were not statistically significant. Conclusion: Medication errors appear to occur independently of medication regimen complexity. Critical care pharmacists were responsible for mitigating a large number of medication errors. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of tofacitinib in patients with ankylosing spondylitis (AS) by prior biologic disease‐modifying antirheumatic drug (bDMARD) use. Methods: Data from a placebo‐controlled, double‐blind study of patients with active AS were analyzed. Patients received tofacitinib 5 mg twice daily (BID) or placebo to week 16; all received open‐label tofacitinib 5 mg BID to week 48 and were stratified by prior treatment (bDMARD‐naive or tumor necrosis factor inhibitor [TNFi]–inadequate responder [IR], including bDMARD‐experienced [non‐IR]). Disease activity/safety were assessed throughout. Results: Of 269 patients, 207 (77%) were bDMARD‐naive; 62 (23%) were in the TNFi‐IR subgroup. TNFi‐IR patients had higher baseline BMI (28.0 vs. 26.1 kg/m2), longer symptom duration (14.4 vs. 13.2 years), and lower concomitant conventional synthetic DMARD use (14.5% vs. 30.9%) than bDMARD‐naive patients. At week 16, for most outcomes, tofacitinib efficacy exceeded placebo for both subgroups and was sustained to week 48. At week 16, tofacitinib versus placebo differences were similar between bDMARD‐naive and TNFi‐IR patients (Assessment in Spondyloarthritis international Society 40 treatment difference [95% confidence interval]: 30.8% [19.1%‐42.6%] vs. 19.4% [1.7%‐37.0%]). Adverse event (AE) proportions were similar between tofacitinib‐treated bDMARD‐naive/TNFi‐IR patients (77.5%/77.4%) at week 48 with no deaths. A numerically higher proportion of tofacitinib‐treated TNFi‐IR versus bDMARD‐naive patients discontinued study drug (12.9% vs. 3.9%) or dose reduced/temporarily discontinued due to AEs (19.4% vs. 11.8%). Conclusion: Tofacitinib efficacy exceeded placebo at week 16 for bDMARD‐naive/TNFi‐IR patients and was sustained to week 48. The absolute magnitude of responses was generally greater in bDMARD‐naive patients versus TNFi‐IR patients. More TNFi‐IR versus bDMARD‐naive patients discontinued or dose reduced/temporarily discontinued tofacitinib due to AEs. Small sample size and sample size differences between subgroups limited the interpretation. [ABSTRACT FROM AUTHOR]

We report a case of a 46‑year‑old female – a postrenal transplant patient, having developed rhabdomyolysis and neuroleptic malignant syndrome (NMS), after 2.5 months of desidustat initiation – for anemia. Post renal transplant anemia (PTA) is common among renal transplant recipients. Apart from treating it with iron supplements, folic acid, andrecombinant human erythropoietin (EPO), novel agents like hypoxia‑inducible factor–prolyl hydroxylase domain (HIF–PHI) are also used, with a very few studies available on its efficacy and safety in PTA patients. Anemia occurring in the first 6 months is called early PTA – occurring most commonly due to iron deficiency, while anemia occurring after 6 months is called late PTA– associated with impaired graft function. The optimal target of hemoglobin in transplant recipients is 12.5–13 gm/dl, which is higher than targets in chronic kidney disease patients. NMS is a life‑threatening emergency – mainly seen in patients on antipsychotic medications. It needs to be differentiated from other closely related conditions such as central nervous system infections(meningitis and encephalitis), tetanus, heatstroke, serotonin syndrome, and thyrotoxicosis. Desidustat is an oral HIF–PHI that stimulates erythropoiesis by preventing EPO degradation. Its adverse effects include high blood pressure, myocardial infarction, heart failure, high potassium, and dizziness; however, there is only one case report of rhabdomyolysis associated with desidustat, and none of NMS. It is, therefore, important to be aware of this potential severe side effect of the drug that was not known earlier so that practicing physicians can be vigilant of the same. [ABSTRACT FROM AUTHOR]

Background: This study aims to estimate the safety, efficacy, and median effective dose (ED50) of esketamine for preventing early postoperative pain in patients undergoing laparoscopic cholecystectomy. Methods: 54 patients undergoing laparoscopic cholecystectomy were prospectively randomized into two groups (group C and group E). Different doses of esketamine were intravenously administered before the skin incision in Group E. The patients in group C received the same dose of saline at the same time. General population characteristics were recorded. The median effective dose (ED50) and 95% effective dose (ED95) were calculated using Dixon's up-and-down method. Hemodynamic parameters were monitored, and pain intensity was assessed using a visual analog scale. We also recorded the condition of anesthesia recovery period and postoperative adverse reactions. Results: The ED50 of esketamine for preventing early postoperative pain was 0.301 mg/kg (95%CI: 0.265-0.342 mg/kg), and the ED95 was 0.379 mg/kg (95%CI: 0.340-0.618 mg/kg), calculated by probability unit regression. Heart rate (HR) was significantly lower in the esketamine group compared to the control at the skin incision (p < 0.05). The total VAS score at resting was significantly lower in the esketamine group compared to the control group during the awakening period (p < 0.05). There was no significant difference between the two groups regarding the incidence of adverse reactions (p > 0.05). Conclusions: In this study, esketamine can prevent early postoperative pain effectively. The ED50 and ED95 of esketamine for controlling early postoperative pain were 0.301 mg/kg and 0.379 mg/kg, respectively. Trial registration: ChiCTR2200066663, 13/12/2022. [ABSTRACT FROM AUTHOR]

Objective: Hydroxychloroquine (HCQ) use for the treatment of dermatomyositis (DM) has been associated with adverse cutaneous reactions. We applied a new user, active comparator, retrospective design to assess differences in adverse cutaneous reactions or hospitalizations between HCQ and methotrexate (MTX) use among patients with DM. Methods: We used a national network of data from insurance registries (TriNetX), enrolling patients with two International Classification of Diseases (ICD) codes for DM separated by 6 months or more who had a prescription for either (but not both) HCQ or MTX on or after DM diagnosis. Outcomes were adverse cutaneous reactions (ICD codes) or hospital admission (Current Procedural Terminology (CPT) codes) within 4 months from the prescription dispense date. Logistic regression was used to produce adjusted odds ratios (aORs) and 95% confidence intervals (CIs) comparing outcomes in the HCQ group (n = 1364) and the MTX group (n = 1400), adjusted for age at first DM diagnosis, year of birth, sex, and time from DM diagnosis to first prescription. Results: Overall, we found no significant difference in odds of hospitalization in those taking HCQ (aOR 1.05; 95% CI: 0.79‐1.39) compared with those on MTX. Patients with DM on HCQ had 30% higher odds of adverse cutaneous reaction diagnosis compared with patients on MTX (aOR 1.30; 95% CI: 1.02‐1.59). Age at DM diagnosis was an effect modifier of this association, with higher odds of adverse cutaneous reaction among patients taking HCQ who were younger at diagnosis. Conclusion: Compared with MTX use, HCQ use, especially in younger patients, may result in higher odds of adverse cutaneous reactions. [ABSTRACT FROM AUTHOR]

Introduction: Drug-drug interactions (DDIs) can reduce therapeutic efficacy and increase the duration and cost of hospitalization so that patients are sometimes exposed to significant complications and even death. Patients in the intensive care unit (ICU) are at higher risk of DDIs for a variety of reasons, including impaired absorption, decreased metabolism, and renal failure. The main objective of this study was to evaluate frequency, clinical ranking and risk factors of potential DDIs in the ICUs of 3 teaching hospitals in Ardabil. Methods : In this descriptive-analytical cross-sectional study, drug prescriptions 355 patients admitted to the ICUs were studied. Patient information including age, sex, diagnosis, number of prescribers, number of drugs, length of stay, and status of patients' discharge (recovery or death) were recorded and checked using the online software up to date and the book Drug Interaction Facts. Finally, the data were statistically analyzed using the SPSS software. Results : The number of patients studied was 355. The mean age of the patients were 51.88 ± 23.22 years, and on average, 8.45 drugs had been prescribed for each patient. The total number of DDIs was 1597 among which class X was 1.4%, class D was 26.2%, and class C was 67.7%. Four hundred ninety-seven unique pairs of DDIs were identified. Age, number of prescribed drugs and length of stay in ICU were associated with prevalence of DDIs. Age and number of drugs were also identified as the risk factors of patients' discharge caused by death. Conclusion : DDIs can complicate health state of patients in ICUs and may increase the length of hospital stay. Setting up computerized systems to alert drug interactions in hospital wards and pharmacotherapeutic intervention by clinical pharmacist can minimize DDIs. [ABSTRACT FROM AUTHOR]

Introduction: Adverse drug reactions (ADRs) are unwanted, often harmful reaction resulting from a pharmacological intervention that warrants treatment, prevention, and future precautions. ADRs are highly prevalent with 10%–20% of patients suffering from one when admitted. The aim of this study was to identify cases and provide data on the incidence, severity, causality, and preventability of ADRs in a clinical setting in various age groups. The study also aimed to identify ADR risk factors which can be used to create ADR risk prediction models for application in everyday clinical practice to proactively detect patients at risk of developing these reactions. Materials and Methods: This was an inpatient, prospective, observational cohort study in the internal medicine ward of a major tertiary care hospital. Once the institutional ethics approval was obtained, patients fulfilling the inclusion criteria were enrolled with informed consent. Their data were recorded in an ADR data form. These data were then analyzed using standardized scales to identify causality, severity, preventability, and avoidability along with specific risk factors and comparing them across age groups and drug classes. Results: One hundred and sixty-four patients were eligible and enrolled. Seventy percent of those suffering from ADRs were in the 30–60 years age group. Oral hypoglycemics and antituberculosis drugs were most commonly implicated, whereas metabolic and hepatic systems were the most frequent organ systems involved. Polypharmacy and hypertension were the most common risk factors identified. The cause of 96.3% of ADRs was probable, and 51.2% of the ADRs were categorized as severe. Nearly a fourth of the severe ADRs were categorized as life-threatening. A majority of the ADRs were treated by terminating the suspected drug, and 54% of patients recovered completely. 6.1% of the ADRs were definitely avoidable while 42.1% were unavoidable. Conclusion: This study clearly demonstrates the massive burden of ADRs, both on the patients and the hospitals. There is a dire need for a standardized, easily accessible means of mandatory reporting of ADRs, and that data need to be utilized to treat, decrease morbidity, and prevent ADRs by proactively anticipating them to ultimately improve patient care. The following core competencies are addressed in this article: Patient care, Medical knowledge, Interpersonal and communication skills, Practice-based learning and improvement, and Systems-based practice [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the effect of intravenous (IV) dexamethasone on the duration of hyperbaric bupivacaine spinal anesthesia. Methods: Two hundred patients between the ages of 18 and 60, of both sexes with ASA I- II classification scheduled for lower abdominal surgery under spinal anesthesia using hyperbaric bupivacaine 0.5% were randomly divided into two groups: the dexamethasone group (Dexa group) and the control group, with 100 patients in each group. Before the administration of spinal anesthesia, the Dexa group received an intravenous infusion of 8 mg dexamethasone in 500 mL normal saline, while the control group received 500 mL normal saline only. The primary outcome of this study was to assess the effect of IV dexamethasone on the regression of hyperbaric bupivacaine spinal anesthesia. Secondary outcome measures included the total duration of sensory and motor blocks, VAS score, time of first analgesic request, total analgesic consumption within the first 24 h, and the occurrence of any side effects. Results: The Dexa group had significantly delayed onset of 2 dermatomes regression (P < 0.001) compared to the control group. Additionally, the Dexa group had significantly longer duration of both sensory block (P = 0.01) and motor block (P < 0.001). The Dexa group had significantly longer duration until the first postoperative analgesic request (P < 0.001) and a lower incidence of side effects compared to the control group. Conclusion: Although the intravenous administration of dexamethasone had a limited effect on the duration of hyperbaric bupivacaine spinal anesthesia, it improved postoperative VAS scores compared to the control group and decreased overall postoperative analgesic consumption. Therefore, it can be considered a valuable addition to postoperative multimodal analgesia strategies, aiming to minimize total analgesic consumption. Clinical trial registration: ID: NCT04778189 (2/3/2021). [ABSTRACT FROM AUTHOR]

Dexmedetomidine is a selective alpha-2 adrenergic agonist utilized for sedation in critically ill patients. 1 We present the case of a morbidly obese critically ill patient who experienced profound hyperthermia, with a maximum temperature of 41.4°C, hours after starting a dexmedetomidine infusion that was otherwise not explained by her clinical diagnoses. The hyperthermia resolved hours following cessation of the infusion. Dexmedetomidine was assessed as probable in terms of causing this adverse effect. Dexmedetomidine may be associated not only with low-grade fever, but as demonstrated in our case, it may be associated with significant temperature elevations requiring cessation of therapy to restore normothermia. [ABSTRACT FROM AUTHOR]

Introduction: Although adverse drug reaction (ADR) monitoring is widely known, it is not practised in underdeveloped nations due to a lack of awareness and the absence of a central coordinating agency. The recent implementation of the National Pharmacovigilance Program has encouraged ADR monitoring in some centres. Aim: The purpose of this study was to evaluate the sternness of described ADRs, the additional financial cost associated with ADRs, and the present load of ADRs at the RDT hospital in Battalapalli, AP, India. Materials and Methods: Over 26 months of hospital admissions of patients, which were managed by hospital staff, a prospective, spontaneous reporting research was carried out. Results: 37 of the 74 adverse drug events (ADEs) that were reported by 56 individuals were indeed ADRs. There were 521 patients admitted, and 9.7% of those ADRs occurred during hospitalisation. Males (56%) had ADRs more often than females (44%). During the hospital stay, no discernible difference between males and females was seen. ADR rates were 19, 20, and 61% for paediatric, geriatric, and adult patients. There were 88 minor responses or 53.7% of the total. The majority of patients (72.6%) recovered from the incident. The majority of the responses show that they were unexpected and possibly avoidable. Conclusion: According to the study's findings, 90% of ADRs might be prevented, saving the health system money and decreasing patient expenditures. To prevent unknown and severe ADRs, new medications should be continuously monitored. [ABSTRACT FROM AUTHOR]

Background: Sirolimus is a potent immunosuppressive in renal transplantation. However, its use is limited by some reported side effects. The objective of this study was to determine the side effect profile of sirolimus in renal transplant patients. Materials and Methods: In the present study, we retrospectively reviewed the medical records of 116 renal transplant patients treated with sirolimus alone or in combination with other immunosuppressive agents at private therapeutic centers in Isfahan, Iran, between March 2009 and February 2020. A checklist was used to collect data on demographic and clinical variables. Data were analyzed with independent samples t test and Chi squared test. Results: Our findings indicated that the most prevalent sirolimus related side effects were edema (42.3%), proteinuria (37.5%), cytopenia (26.9%), abnormal level of liver enzymes (11.7%), and pneumonitis (9.7%). Stratification of side effects by sirolimus dose (<2 mg and ≥2 mg) demonstrated their dose independent occurrence (P > 0.05). Pneumonitis was the most frequent reason for sirolimus cessation (58.7%). No significant differences were observed between males and females regarding the frequency of reasons for sirolimus cessation (P > 0.05). Conclusion: Edema, proteinuria, cytopenia, abnormal level of liver enzymes, and pneumonitis were the most prevalent sirolimus related side effects in renal transplant patients. Further prospective cohort studies are warranted to detect underlying mechanisms and determinants of these side effects in renal transplant patients treated with sirolimus. [ABSTRACT FROM AUTHOR]

Background: Postoperative analgesia in breast surgery is difficult due to the extensive nature of the surgery and the complex innervation of the breast; general anesthesia can be associated with regional anesthesia techniques to control intra- and post-postoperative pain. This randomized comparative study aimed to compare the efficacy of the erector spinae plane block and the thoracic paravertebral block in radical mastectomy procedures with or without axillary emptying. Methods: This prospective randomized comparative study included 82 adult females who were randomly divided into two groups using a computer-generated random number. Both groups, Thoracic Paraverterbal block group and Erector Spinae Plane Block group (41 patients each), received general anesthesia associated with a multilevel single-shot thoracic paravertebral block and a multilevel single-shot erector spinae plane block, respectively. Postoperative pain intensity (expressed as Numeric Rating Scale), patients who needed rescue analgesic, intra- and post-operative opioid consumption, post-operative nausea and vomiting, length of stay, adverse events, chronic pain at 6 months, and the patient's satisfaction were recorded. Results: At 2 h (p < 0.001) and 6 h (p = 0.012) the Numeric Rating Scale was significantly lower in Thoracic Paraverterbal block group. The Numeric Rating Scale at 12, 24, and 36 postoperative hours did not show significant differences. There were no significant differences also in the number of patients requiring rescue doses of NSAIDs, in intra- and post-operative opioid consumption, in post-operative nausea and vomiting episodes and in the length of stay. No failures or complications occurred in the execution of techniques and none of the patients reported any chronic pain at six months from the surgery. Conclusions: Both thoracic paravertebral block and erector spinae plane block can be effectively used in controlling post-mastectomy pain with no significant differences between the two blocks. Trial registration: The study was prospectively registered on Clinicaltrials.gov (trial identifier NCT04457115) (first registration 27/04/2020). [ABSTRACT FROM AUTHOR]

Introduction: Acute kidney injury (AKI) is a complex syndrome requiring special management. It also complicates the prognosis of many hospitalized patients. Some essential yet nephrotoxic medications and the use of certain procedures that may alter renal hemodynamics further complicate the management of AKI patients. Fortunately, as part of the renal care team, pharmacists can have a significant role in the multidisciplinary approach used to optimize renal patients' health-related quality of life by delivering safe and effective pharmaceutical care. Objective: The present review aims to explore pharmacists' contributions to the management of patients with AKI as well as their influence on improving renal patients' care. Methods: An online search was performed in the databases PubMed, Scopus, and ScienceDirect for relevant articles published in English between 1 January 2015 and 31 December 2021. Review articles, books, guidelines, websites, and conference proceedings were excluded. Results: Only 12 articles out of 51 initially gathered met the eligibility criteria for this review. The three main roles that pharmacists play in the management of AKI patients are patients' education, collaborating with other renal care practitioners, and identifying and solving drug-related problems (DRPs). The latter task span includes medication reconciliation, dosage adjustments, and identifying adverse drug reactions. Conclusion: In view of the complexity of the AKI course, trained pharmacists, as members of the renal care team, can play a pivotal role in managing AKI patients and minimizing their medications burden. This can positively impact the overall renal care process as well as the patient's outcome. Further studies can provide more support to the importance of pharmacists' role in managing AKI. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the clinical characteristics of pseudocellulitis induced by pemetrexed. METHODS: Case reports on pseudocellulitis induced by pemetrexed were collected by retrieving domestic and foreign databases, relevant information of the patients ( genders, ages, primary diseases, drug combinations, occurrence times, incidences of adverse drug reactions, inspection indicators, main intervention measures and outcomes, reuse or not, etc. ) were extracted for descriptive statistical analysis. RESULTS: A total of 17 cases of pseudocellulitis induced by pemetrexed were collected, including 10 males and 7 females; patients aged from 36 to 79 years old, with a median age of 66 years old. The occurrence time of pseudocellulitis was from the 1st cycle to the 21st cycle after the application of pemetrexed, the median occurrence time was the 4th cycle. The main clinical manifestations were swelling of lower limbs ( 13 cases, 76. 47%), rash ( 13 cases, 76. 47%), pain ( 10 cases, 58. 82%), sclerosis (6 cases, 35. 29%), etc. Seven patients had ineffective initial antimicrobial therapy; four patients switched to topical corticosteroids after ineffective antimicrobial therapy, so that the rash resolved. Four patients had all symptoms relieved after treated with initial oral or topical glucocorticoids. Most patients were improved after treatment, one patient died due to exacerbation of primary disease, and two patients had persistent sclerosis of the rash site. CONCLUSIONS: The clinical manifestations of pseudocellulitis induced by pemetrexed are mainly swelling of lower limbs, rash, pain and sclerosis, most patients are improved after treatment, while a few may have persistent sclerosis of the rash site. If symptoms similar to cellulitis appear after using pemetrexed, the differential diagnosis with infectious disease cellulitis should be made promptly, and oral or topical corticosteroid drugs should be given to ensure the safety of patients. [ABSTRACT FROM AUTHOR]

Introduction: Pantoprazole is a proton pump inhibitor (PPI) class drug that is widely used in the treatment of SRMD (stress-related mucosal disease in critical ill patients. PPI are one class of drugs used commonly both for treatment and prophylactic therapy for stress ulcers in intensive care unit (ICU). Case: We report a case of a 51-year old male who was referred to PKU Hospital. He was admitted to ICU with diagnosis of Hyperosmolar Hyperglymic State and bronchopneumonia. Thrombocytopenia was noted in admission. There was more than 70% decrease in platelet count after initiation of pantoprazole. Patient received Thrombocyte Concentrate (TC) transfusion and corticosteroid iv for several days, but only had minor increase in platelet count. The platelets recovered after stopping pantoprazole. Discussion: In the present case report, another exposures to parenteral pantoprazole in a dose of 40 mg once daily reproduced the same adverse drug reaction. In comparison to lansoprazole, thrombocytopenia from pantoprazole is more severe that necessitate TC transfusion and corticosteroid trial. However, in the present case, TC transfusion and corticosteroid fail to escalate platelet count. This finding suggests probability of non-immune mechanism of pantoprazole-induced thrombocytopenia. Conclusion: Pantoprazole may induce thrombocytopenia with new features that were immediately developed, resulting a decrease in platelet count >70%. The mechanism found in this case may be non-immune. Drug-induced thrombocytopenia is one of the rare complications that has to be kept in mind with the use of pantoprazole. [ABSTRACT FROM AUTHOR]

BACKGROUND: Renal transplant patients receive several drugs concomitantly. OBJECTIVE: Limited literature exists evaluating the drug use in this population that is at high risk for drug-induced acute kidney injury and complications due to under-or over-dosage of immunosuppressant drugs due to drug–drug interactions. METHODS: A retrospective observational study was carried out in 269 renal transplant patients in whom either oral or parenteral drugs were evaluated. World Health Organization (WHO) indicators of drug utilization such as the average number of drugs prescribed, daily defined dose, and proportion of drugs listed as WHO essential drugs were evaluated. Details on the drugs with nephrotoxic potential were obtained. Drug–drug interactions were assessed concerning the severity (major, moderate, and minor) as well as type (pharmacokinetic, pharmacodynamic, and toxicity). RESULTS: One-hundred and ninety-eight drugs were administered to the study participants. The median (range) total number of drugs received by the study participants was 23 (6–55). The proportion of drugs listed in the WHO essential drug database was 57.1 (16.7–100)%. Forty-six drugs with potential nephrotoxicity and seven drugs that were contra-indicated in patients with chronic renal disease/end-stage renal disease were administered to the study participants. The mean (SD) numbers of drug interactions observed amongst the study participants were 18.4 (10.1). Age (β: 0.2, 95% CI: 0.1, 0.3) and duration of renal transplantation (β: −0.3, 95% CI: −0.5, −0.1) were the significant predictors of drug burden. A total of 645 drug interactions were identified amongst the study participants (major – 240; moderate – 270; and minor – 135) of which the majority were pharmacokinetic followed by toxicity risk. Age was significantly associated with the risk of potential drug interaction (OR: 2.6, 95% CI: 1.8, 12.4; p = 0.001). CONCLUSION: Drug treatment in renal transplant patients poses a significant burden in terms of nephrotoxicity potential and drug–drug interactions. A dedicated ambulatory clinical pharmacy service monitoring the drug use coupled with drug deprescribing strategies are the need of the hour in this population. [ABSTRACT FROM AUTHOR]

Adverse drug reactions (ADRs) are responsible for almost 5% of hospital admissions, making it necessary to implement different pharmacovigilance strategies. The additional monitoring (AM) concept has been highlighted and intended to increase the number of suspected ADRs reported, namely in medicines with limited safety data. A prospective, descriptive study of active pharmacovigilance (AP) was conducted between 2019 and 2021 in the Local Health Unit of Matosinhos (LHUM) (Porto, Portugal). A model of AP for medicines under AM, namely oral antineoplastic agents, was designed. Follow-up consultations were performed, and adverse events (AEs) data were collected. The overall response to the treatment was evaluated through the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. A total of 52 patients were included in the study, and 14 antineoplastic drugs under AM were analyzed. Of the total number of patients included, only 29 developed at least one type of toxicity. Hematological disorders were the most reported suspected ADR. However, only four patients interrupted their treatment due to toxicity. After 12 months of treatment, most patients had disease progression, which was the main reason for therapy discontinuation. This AP model played an important role in the early detection of AEs and, consequently, contributed to better management of them. Increasing the number of suspected ADR reports is crucial for drugs with limited safety data. [ABSTRACT FROM AUTHOR]

Background: Enoxaparin is commonly used for venous thromboembolism (VTE) prophylaxis in hospitalized patients. Published literature exists for dose adjustment in higher body weights and renal dysfunction, but sparse literature on optimal dosing of prophylactic enoxaparin in underweight patients exists. Objective: To determine if there is a difference in adverse outcomes or effectiveness if enoxaparin VTE prophylaxis dosing is reduced to 30 mg subcutaneously once daily from standard dosing in underweight medically ill patients. Methods: This study was a retrospective chart review of a total of 171 patients, with 190 individual courses of enoxaparin included. Patients were ≥18 years of age, weighed ≤50 kg, and were given at least 2 days of consecutive therapy. Patients were excluded if they were taking anticoagulation upon admission, had a creatinine clearance <30 mL/min, were admitted to the ICU or a trauma or surgical service, or presented with bleeding or thrombosis. The Padua score and a modified score from the IMPROVE trial were used to evaluate baseline thrombotic risk and bleeding risk, respectively. Bleeding events were classified using the Bleeding Academic Research Consortium criteria. Results: No difference was seen in baseline risk of bleeding or thrombosis when comparing the reduced and standard dosing groups. No differences were observed with rates of bleeding, thrombotic events, mortality, or 30-day readmission. Conclusion: Both reduced and standard dosing strategies appeared effective for VTE prophylaxis, but neither showed superiority in reducing bleeding events. Additional larger studies are needed to evaluate safety and effectiveness of reduced dose of enoxaparin in this patient population. [ABSTRACT FROM AUTHOR]

Objective A significant variability exists for diagnosis and treatment of hypotension in extremely preterm infants. Benefits of the use of vasopressors remain unclear. We wanted to identify the risk factors associated with use of vasopressors in the first week of life and their impact on outcomes of extremely preterm infants. Study Design Retrospective review of all newborns ≤28 weeks of gestational age (GA) admitted in neonatal intensive care unit from October 1, 2012, to October 31, 2015, done. Data regarding antenatal and neonatal characteristics and outcomes were recorded. Study infants were divided into two cohorts and compared based on vasopressor use. Chi-square, t -test, and multiple logistic regression were performed as appropriate and significance set at p <0.05. Results Of 213 extremely preterm infants, 90 (42.3%) received vasopressors in first week of life. The mean arterial pressure (MAP) at admission in these infants was significantly lower than that of infants who did not require vasopressors (27 ± 8 vs. 30 ± 6 mm Hg, p < 0.05). Vasopressors were initiated within 24 hours in 91% of babies. After controlling for other variables, use of vasopressors was significantly higher in infants with lower birth weight (odds ratio [OR]: 3.2, 95% confidence interval [CI]: 1.6–8.3), 5-minute Apgar's score ≤5 (OR: 1.8, 95% CI: 1.2–3.12), and admission hypothermia (OR: 2.7, 95% CI: 1.3–4.9). The use of vasopressors was significantly associated with severe intraventricular hemorrhage (IVH), even after controlling for other significant variables (OR: 5.9, 95% CI: 1.6–9.3). Conclusion Lower birth weight, low 5-minute Apgar's score, and admission hypothermia are characteristics associated with early use of vasopressors in extremely preterm infants. Infants treated with vasopressors are at a higher risk of developing severe IVH. Key Points Low systemic blood pressure is a very common problem in the extremely preterm population. In clinical practice, mean arterial blood pressure (BP) less than the infants GA in week is typically considered to be "low BP." About 50% of infants born at <29 weeks of GA received very preterm in the first week of life. Use of vasopressors is associated with a higher incidence of intraventricular hemorrhage in extremely preterm population. [ABSTRACT FROM AUTHOR]

Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) are often recommended as opioid-sparing agents. The objective of this scoping review was to conduct a thorough search of the current literature to determine whether in adult critically ill patients there is an association between exposure to NSAIDs vs no NSAIDs and the subsequent development of serious adverse events, particularly gastrointestinal bleeding and acute kidney injury (AKI). Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews was utilized as a guideline for reporting. Searches were performed in PubMed (National Library of Medicine), Cochrane Library (Wiley), EMBASE (Elsevier), Stat!Ref (Teton), and Access Pharmacy (McGraw Hill) for articles published from January 2016 to August 2022. Results Of the 3,062 citations and titles identified in the search, 2,737 titles remained after removal of duplicates, 2,588 were excluded at title and abstract screening, and 149 articles remained for full-text review. None of the studies involved heterogeneous groups of critically ill patients in nonspecialty intensive care unit settings. Most studies evaluated were conducted in the perioperative setting and had limited adverse events reporting, particularly with respect to serious NSAID-related adverse effects of concern in critically ill patients. Conclusion In published studies primarily involving perioperative patients, there is insufficient detail concerning the definitions and reporting of NSAID-related serious adverse events such as bleeding and AKI. These events are of particular concern in heterogeneous critically ill patient populations predisposed to such complications. In most (if not all) critically ill patients, sustained dosing of NSAIDs should be avoided regardless of COX-1 selectivity due to the paucity of safety data. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the clinical efficacy of lorlatinib in the treatment of non-small cell lung cancer (NSCLC) based on Meta-analysis method, and to probe into the clinical manifestations, characteristics, patterns and outcomes of adverse drug reactions (ADR) induced by lorlatinib, so as to provide references for the clinical safe medication. METHODS: By retrieving CNKI, Wanfang Data, PubMed, Web of Science and other database, randomized controlled trials (RCT) on lorlatinib in the treatment of NSCLC [the lorlatinib group was given lorlatinib regimen with or without other medication, and the control group was given the first and (or) the second generation of anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (TKI) regimen] were enrolled for Metaanalysis, and studies on ADR induced by lorlatinib were also analyzed. RESULTS: Totally 5 eligible RCT were enrolled, including 622 patients (308 cases in the lorlatinib group, 314 cases in the control group), the objective remission rate (ORR) was used as the main outcome indicator. The results of Meta-analysis showed that the ORR of the lorlatinib group was higher than that of the control group, with statistically significant difference(OR = 2. 31,95%CI = 1. 62-3. 28,P<0. 000 01), which indicated that the efficacy of lorlatinib was significant compared with the previous 2 generations of drugs. Fourteen cases of ADR induced by lorlatinib were also collected, including 6 male patients and 8 female patients; there were more patients in the age group of >60 to 70 years old, with 7 cases; most ADR occurred at 2 weeks after medication, mainly involved cardiovascular system damage and respiratory system damage; all ADR were improved after drug withdrawal and (or) symptomatic supportive treatment; 2 cases showed no improvement or aggravation of symptoms at recurrence. CONCLUSIONS: As the third generation of ALK-TKI to treat NSCLC, the level of loratinib to treat NSCLC was significantly improved. However, clinical application of lorlatinib requires strict monitoring on cholesterol and triacylglycerol levels, as well as vigilance against central nervous system damage and cross-adverse drug reactions in the early phase of drug administration. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant and adjuvant immune checkpoint inhibitor treatments for non-small cell lung cancer (NSCLC) patients with resectable disease have presented promising results. This is a phase I study to evaluate the safety and efficacy of neoadjuvant toripalimab in combination with chemotherapy for NSCLC. Methods: Treatment-naive patients with resectable NSCLC (stage II–IIIB) received two to four cycles of toripalimab (240 mg, intravenously, q3w) combined with platinum-paclitaxel chemotherapy. Surgical operation was performed approximately 4 weeks after the last cycle. The primary end point was safety. The efficacy endpoints included radiographic and pathological response rates, expression of programmed death ligand 1 (PD-L1) and molecular targets. Results: A total of 11 patients were enrolled, consisting of 2 patients (18%) with adenocarcinoma and 9 patients (82%) with squamous cell carcinoma. All patients received two to four cycles of toripalimab plus chemotherapy and underwent radical resection. Regarding safety, 5 of 11 patients (45%) had neoadjuvant treatment-related adverse events, and 1 patient (9%) experienced grade 3 or worse treatment-related adverse events. Radiographic partial response was achieved in 10 patients, with an objective response rate of 91%. Among 11 patients, 6 (55%) achieved pathological complete response, including 1 PD-L1-negative patient. Conclusion: Neoadjuvant toripalimab plus platinum-paclitaxel chemotherapy was tolerable and induced a pathological complete response in 55% of resectable NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Immune-related adverse events (irAEs) are a common phenomenon in cancer patients treated with immune checkpoint inhibitors (ICIs). Surprisingly, the toxicity burdens of these irAEs have not been illustrated clearly. In this study, we analyzed irAEs for seven FDA-approved ICIs in cancer treatment to show the pattern of toxicity burden among cancer patients. Methods: irAEs associated with seven FDA-approved ICIs, including three PD-1 inhibitors (cemiplimab, nivolumab and pembrolizumab), three PD-L1 inhibitors (atezolizumab, avelumab and durvalumab), and one CTLA-4 inhibitor (ipilimumab), were analyzed based on data from 149,303 reported cases (from January 1, 2015 to June 30, 2022) collected from the FDA Adverse Events Reporting System (FAERS) public dashboard. Proportions of serious irAEs and correlations with tumor type, age and sex were assessed via R package and GraphPad software. Results: irAEs related to anti-PD-1 ICIs required less hospital care resources compared with anti-PD-L1 and anti-CTLA-4 ICIs. Patients treated with pembrolizumab had relatively fewer serious cases. Treatment with ICIs led to the highest probability of serious irAEs in patients with lung cancer. 'Respiratory, thoracic and mediastinal disorders' and 'gastrointestinal disorders' were the two most common groups of disorders caused by the seven ICIs studied. 'Cardiac disorders' was the main type of disorders caused by these ICIs in cancer patients aged 65–85, while 'reproductive system and breast disease' was the main type of disorder in cancer patients aged 18–64. 'Respiratory, thoracic, mediastinal diseases' and 'reproductive system and breast diseases' were the main types of disorders associated with treatment with these ICIs in male and female patients, respectively. Conclusion: Tissue and organ toxicities of ICIs are age and sex specific. There are risks of respiratory and urinary system toxicity in male patients and reproductive system toxicity in female patients treated with the ICIs studied. Future studies on the toxicity burden of ICIs should incorporate age and sex differences to better understand the relevance of ICI toxicity burden to human immune function to develop appropriate tumor immune and therapeutic intervention strategies. [ABSTRACT FROM AUTHOR]

Introduction: Immune-related adverse events are complications of immune checkpoint inhibitors which require robust patient education and proactive follow-up to ensure timely identification and management. Oncology pharmacist practice models with other anticancer modalities have been well documented, but there is limited evidence assessing the spectrum of pharmacist interventions in patients receiving immune checkpoint inhibitor(s) and the impact of these interventions on patient outcomes. Methods: Patients initiated on immune checkpoint inhibitor(s) from 1 January 2016 to 31 August 2019 were included for data collection and analysis. Part 1 featured an intensive pharmacist follow-up cohort (study cohort) and summarized pharmacist interventions. Part 2 compared patient outcomes between the study cohort and a standard of care cohort (control cohort) from a different oncology centre. Patient outcomes included emergency department visits not resulting in admission, hospitalizations due to immune-related adverse event(s), immune checkpoint inhibitor cycles received, treatment discontinuation due to immune-related adverse event(s), completion of finite programmed death-1/death-1 ligand treatment course and completion of ipilimumab. Clinical outcomes were compared using a retrospective, matched cohort design based on age, cancer diagnosis and immune checkpoint inhibitor(s). Results: A total of 143 patients were included in Part 1 encompassing 1664 pharmacist recommendations across 11 categories. The matched cohort yielded 92 matches (n = 184) with a higher odds of immune checkpoint inhibitor discontinuation due to immune-related adverse event(s) in the control cohort (odds ratio (OR) (95% confidence interval (CI)) = 5.5 (1.2−24.8); p = 0.022). Conclusion: Intensive immune-related adverse event education, proactive follow-up and immune-related adverse event management by pharmacists result in clinically meaningful interventions which correlate to improved patient outcomes, namely lower odds of treatment discontinuation due to immune-related adverse event(s). [ABSTRACT FROM AUTHOR]

Proton-pump inhibitors (PPIs), are powerful and effective anti-secretory, used for many years, with precise indications and in the vaste majoritary of cases for a limited times. Unfortunately, a number of prescription “drifts” exist, with sometimes negative consequences for patients. Moreover, many adverse effects, related to taking these treatments, are now well known and documented. We propose in this summary article, a summary of these adverse reactions, who must be known by the polyvalent practitioner in his daily practice. [ABSTRACT FROM AUTHOR]

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive age-related lung disease causing relentless fibrosis of the lung parenchyma. Currently, pirfenidone and nintedanib are the two antifibrotic drugs, approved for the treatment of IPF. Both are shown to slow progression by preserving lung functions from rapid decline compared to a placebo. We are reporting a real-life patient experience using these two antifibrotic medications (AFMs) in our tertiary care hospital. METHODS: A retrospective cohort study was conducted for all IPF cases diagnosed in multidisciplinary meetings between 2015 and 2020 at KAMC, Riyadh (Saudi Arabia). We are reporting patients' demographics, lung function, survival, tolerance, side effects, or death in patients taking AFMs. RESULTS: A total of 81 cases were identified. The majority of patients aged 67 years (68%) were men with a median age of 68 years. Late presentation, severe disease, and definite usual interstitial pneumonia patterns were reported in 60% of our patients. The average number of hospital admissions before starting treatment was 1 (range: 0–3) in the nintedanib group and 1.4 (range: 1.2–5) in the pirfenidone group. There was an increase in the number of hospital admissions in the group started on pirfenidone 1.7 (range: 1.9–8) compared to nintedanib 0.5 (range: 0–3), P = 0.001. The observed mortality outcome in this cohort was 4 (11%) and 12 (27%) for nintedanib and pirfenidone, respectively. The predominant side effects were gastrointestinal symptoms for both the groups 18 (22%). CONCLUSIONS: Pirfenidone and nintedanib are the available approved antifibrotic agents used for many years to treat IPF patients. Real-life data showed better tolerability than reported in the West, good compliance, and a manageable side effect profile in this group of elderly and severe IPF patients. [ABSTRACT FROM AUTHOR]

Background: Critically ill neonates are at greater risk for adverse drug reactions (ADRs). The differentiation of ADRs from reactions associated with organ dysfunction/immaturity or genetic variability is difficult. Methods: In this prospective cohort study, each ADR was assessed using newborn-specific severity and probability scales by the clinical pharmacist. Subsequently, a machine learning-based risk score was designed to predict ADR presence in neonates. Results: In 98/412 (23.8%) of (56.3%; male) neonates included, 187 ADRs (0.42 ADR/patient) were determined related to 49 different drugs (37.12%). Drugs identified as high risk were enoxaparin, dexmedetomidine, vinblastine, dornase alfa, etoposide/carboplatin and prednisolone. The independent variables included in the risk score to predict ADR presence, according to the random forest importance criterion, were: systemic hormones (2 points), cardiovascular drugs (3 points), diseases of the circulatory system (1 point), nervous system drugs (1 point), and parenteral nutrition treatment (1 point), (cut-off value: 3 points). This risk score correctly classified 91.1% of the observations in the test set (c-index: 0.914). Conclusions: Using the high-performing risk score specific to neonates, it is expected that high-risk neonatal ADRs can be determined and prevented before they occur. Moreover, the awareness of clinicians of these drugs can be improved with this web-tool, and mitigation strategies (change of drug, dose, treatment duration, etc.) can be considered, based on a benefit-harm relationship for suspected drugs with a newborn-centered approach. [ABSTRACT FROM AUTHOR]

Introduction: Given the negative outcomes associated with uncontrolled diabetes mellitus, non-insulin therapies with glycemic, cardiovascular, and weight-loss benefits in the general population, such as the glucagonlike peptide-1 receptor agonists (GLP1-RA) have become a more alluring therapeutic option in transplant populations. However, limited evidence exists to demonstrate its safety and efficacy in solid organ transplant. Methods: This program evaluation included adult kidney, liver, lung transplant recipients initiated on a GLP1-RA for diabetes mellitus management for a minimum of 3 months, had at least one follow-up visit after starting therapy, and had at least one hemoglobin A1c (HbA1c) level drawn between 3–12 months after GLP1-RA initiation. Outcomes were assessed at time of initiation of GLP1-RA (baseline) and 3–12 months post-initiation. Nadir values between 3–12 months were utilized to assess outcomes. Results: One-hundred eighteen patients met study inclusion criteria. Seventy-percent of patients received a kidney transplant, 19.5% received a liver transplant, and 6.8% received a lung transplant. A statistically significant difference was observed in median fasting blood glucose and HbA1c at baseline to 3–12-month nadir (P < 0.0001). A significant weight loss benefit was also observed. The rate of adverse drug reactions was low. Seven-percent of patients experienced nausea, 4.2% developed pancreatitis, and 7.1% reported having had at least one hypoglycemic event. Discussion: This is the largest study evaluating GLP1-RA in organ transplantation and demonstrates GLP1-RA is both safe and effective. Further assessment on long-term use of these agents on cardiovascular and renal outcomes is still needed. [ABSTRACT FROM AUTHOR]

What is known and objective: Pain is the main symptom of herpes zoster (HZ), whilst postherpetic neuralgia (PHN) is a long‐term unbearable pain, which seriously affects the quality of life of patients and is also the most intractable problem for clinicians. Early antiviral treatment is considered as a key measure to reduce acute pain and PHN. Nevertheless, most patients still have long‐term pain after 7 days of antiviral treatment, and some patients will develop PHN. This study aimed to investigate whether prolonged duration of antiviral therapy could reduce HZ acute pain and the occurrence of PHN. Methods: The outpatient data of HZ patients over 50 years old who visited the Dermatology Department from January 2016 to May 2018 were retrospectively analysed. According to the different courses of treatment of famciclovir (FCV), the patients were divided into 7‐day FCV group and 14‐day FCV group. The numerical rating scale (NRS) score at the first visit and on the 7th, 14th and 21st days after the start of treatment, the adverse drug reactions and the incidence of PHN were compared between the two groups. Results: A total of 219 patients were involved in the analysis. For acute pain control, the 14‐day FCV group was better than the 7‐day FCV group. For patients with mild initial pain, there was no significant difference in NRS between the two treatments. For patients with moderate‐to‐severe initial pain, the NRS in the 14‐day FCV group was significantly lower than that of the 7‐day FCV group on the 14th and 21st days after starting treatment. PHN occurred in patients with moderate‐to‐severe initial pain, and the incidence was significantly lower in the 14‐day FCV group than in the 7‐day FCV group. There was no significant difference in the number of adverse reactions between the two groups. What is new and conclusion: Compared with the traditional 7‐day antiviral therapy, the 14‐day course of FCV can reduce the acute pain and the incidence of PHN in elderly patients with HZ, especially in patients with moderate to severe initial pain. Prolonging the course of medication did not increase the side effects. [ABSTRACT FROM AUTHOR]

Objective: To study the efficacy and safety profile of ketorolac in cleft palate surgery. Design: Retrospective analysis of patients who underwent primary cleft palate surgery and received either postoperative ketorolac or opioids. Setting: Tertiary care children's hospital. Patients, Participants: Eighty-nine patients enrolled who were all younger than 36 months of age, not dependent on a gastrostomy tube, with no history of bleeding disorders, and had undergone their primary cleft palate procedure by one specific surgeon between January 2010 and June 2019. Interventions: n/a. Main Outcome Measure: Morphine equivalent dose (MED), Face, Legs, Activity, Cry, Consolability (FLACC) score, length of stay (LOS), total oral intake (mL), total oral intake/LOS, and postoperative adverse events between ketorolac and no ketorolac groups. Results: MED, FLACC score, and LOS were significantly lower in the ketorolac group compared to the no ketorolac group. One patient in the ketorolac group had a bleeding event. Conclusions: Use of ketorolac significantly decreased narcotic usage and pain scores as reported by the FLACC score. Moreover, postoperative bleeding was rare in both ketorolac and no ketorolac groups. [ABSTRACT FROM AUTHOR]

Background: The interaction between azole antifungal therapy and immunosuppressant tacrolimus (TAC) is a barrier to use. Objective: This study quantified the drug interaction between low-dose fluconazole (LDF) and TAC to determine the appropriate TAC dose adjustment when used concurrently in renal transplant recipients. Methods: We conducted a single-center retrospective chart review of renal transplant patients > 18 years who received LDF or nystatin (NYS), and TAC. The primary outcome was the difference in tacrolimus total daily dose (TAC TDD) for LDF versus NYS groups. Secondary outcomes included days with supratherapeutic, therapeutic and subtherapeutic tacrolimus levels, time to therapeutic level, incidence of adverse drug reactions and graft rejection. Results: We evaluated 94 patients and included 81. Low-dose fluconazole received a greater TAC TDD prior to post-operative day (POD) 10 (10.5 ± 4.7 mg vs. 7.1 ± 4.5 mg, p < 0.001), but a decreased TAC TDD POD 10 - 30 (8.6 ± 2.2 mg vs. 9.8 ± 0.8 mg, p < 0.001) and following LDF discontinuation (6.9 ± 0.1 mg vs. 9.0 ± 0.4 mg, p < 0.001). Low-dose fluconazole had more patient-days with supratherapeutic (17.9 ± 7.0 vs. 13.9 ± 8.5; p = 0.02) but fewer with subtherapeutic (6.7 ± 5.7 vs. 12.9 ± 7.2; p < 0.01) TAC levels. There was no difference in patient-days with therapeutic TAC levels (15.9 ± 5.8 vs. 14.4 ± 6.6, p = 0.28), meanwhile LDF required less patient-days to therapeutic TAC level (7.1 ± 2.7 vs. 11.5 ± 7.7; p < 0.01). There was no difference in adverse drug reactions between groups and no incidence of graft rejection. Conclusion: A 20% reduction in TAC TDD is warranted in renal transplant patients when used concomitantly with LDF to achieve therapeutic levels. [ABSTRACT FROM AUTHOR]