Medicine (Baltimore). 2023 Dec 8;102(49):e35926. doi: 10.1097/MD.0000000000035926.

ABSTRACT

BACKGROUND: Despite the availability of numerous treatment options, many patients with gastritis experience only partial symptom relief. CKD-495, a newly developed product with the active ingredient extracted from Cinnamomum cassia Presl., has demonstrated anti-inflammatory and antioxidant activity in vitro and an in vivo protective effect against gastric damage by stimulating mucus secretion. This study compared the efficacy and safety of CKD-495 with Artemisiae argyi folium (AAF) for the treatment of acute and chronic gastritis. AAF, a gastric mucosa protective agent that promotes gastric mucosa regeneration, has been used clinically for about 20 years.

METHODS: This phase III multicenter, randomized, double-blind, parallel-group trial (ClinicalTrials.gov; NCT04255589) assigned 242 patients with endoscopically-proven gastric mucosal erosions to receive CKD-495 75 mg (n = 122) or AAF 60 mg (n = 120), respectively, with placebo (for double-blind purposes) 3 times a day for 2 weeks. The primary efficacy endpoint was the erosion improvement rate. Secondary endpoints included erosion cure rates, and improvement rates for edema, redness, hemorrhage, and gastrointestinal (GI) symptoms. Drug-related adverse events were evaluated.

RESULTS: The erosion improvement rate was significantly higher in the CKD-495 group than in the AAF group for both the full analysis set (55.9% vs 39.4%, P = .0063) and per-protocol set (54.6% vs 38.2%, P = .0084). In addition, the erosion improvement rate in patients with acute or chronic gastritis showed that the CKD-495 group had better improvement of erosion than the AAF group, especially in patients with chronic gastritis. Analysis of secondary endpoints, which included erosion cure rate and the improvement rates of edema, redness, hemorrhage, and GI symptoms, showed that the CKD-495 group was more effective than the AAF group. There were no significant between-group differences in safety profiles. No serious adverse events or adverse drug reactions occurred.

CONCLUSIONS: These results demonstrate that CKD-495 75 mg is superior to AAF 60 mg in terms of the endoscopic improvement rate of erosions in patients with acute or chronic gastritis. This new mucoprotective agent, CKD-495, can be considered the therapy of choice for symptomatic relief and healing of gastritis.

PMID:38065906 | DOI:10.1097/MD.0000000000035926

Am J Hematol. 2023 Dec 8. doi: 10.1002/ajh.27080. Online ahead of print.

ABSTRACT

Avatrombopag is a newer thrombopoietin receptor agonist (TPO-RA) currently approved to treat chronic ITP (duration >12 months). No studies have yet evaluated the safety and effectiveness of avatrombopag in newly diagnosed ITP (duration <3 months) or persistent ITP (duration 3-12 months), and so its use in these populations is presently off-label worldwide. We hypothesize that avatrombopag has similar safety and effectiveness irrespective of ITP disease phase. To evaluate this, we performed a multicenter observational cohort study of adults with ITP treated with avatrombopag, comparing patient outcomes by disease phase (newly diagnosed/persistent versus chronic). Seventy-five patients were included, 23 with newly diagnosed/persistent ITP (17.7 patient-years of avatrombopag treatment) and 52 with chronic ITP (65.3 patient-years of avatrombopag treatment). On avatrombopag, 91% of newly diagnosed/persistent patients versus 96% of chronic patients (p = .58) achieved a platelet response (≥50 × 109 /L) and 86% versus 81% of patients (p = .78) achieved a complete response (≥100 × 109 /L). Median platelet counts on avatrombopag were similar between the two groups (165 × 109 /L vs. 129 × 109 /L, p = .57). Response durability was high and similar in both groups. No patients in the newly diagnosed/persistent group had a major bleeding event, thromboembolic event or avatrombopag discontinuation for adverse events, compared with 4, 1, and 2, respectively, in the chronic group. Thrombocytosis (platelets ≥400 × 109 /L) incidence was similar in the two groups. No other drug-related adverse events occurred in either group. Avatrombopag was safe and effective in patients with newly diagnosed and persistent ITP, with outcomes numerically, statistically, and clinically similar to patients receiving avatrombopag for chronic ITP.

PMID:38063420 | DOI:10.1002/ajh.27080

Cancer Med. 2023 Dec 8. doi: 10.1002/cam4.6786. Online ahead of print.

ABSTRACT

BACKGROUND: Fruquintinib has demonstrated significant improvement in overall survival (OS) among previously treated metastatic colorectal cancer (mCRC) patients. However, the utilization of fruquintinib has been constrained by various toxicities, such as hand-foot skin reaction (HFSR) and hypertension, particularly in elderly patients with reduced tolerance to the standard dosage. This study aims to investigate the efficacy and safety of fruquintinib dose-escalation strategy for elderly refractory mCRC patients.

PATIENTS AND METHODS: This open-label, single-arm, phase II trial included patients aged 65 years or over with mCRC who had progressed after two or more lines of chemotherapy. Fruquintinib was administered for 21 consecutive days of a 28-day treatment cycle. The starting dose of fruquintinib was 3 mg/day and escalated to 4 mg/day in Week 2 and 5 mg/day in Week 3 if no significant drug-related toxicity was observed. The highest tolerated dose from Cycle 1 would be administered in Cycle 2 and all subsequent cycles. Before commencing treatment, all enrolled patients underwent a G8 questionnaire and comprehensive geriatric assessments. The primary endpoint of the study was progression-free survival (PFS).

RESULTS: A total of 29 patients were enrolled and all started fruquintinib at 3 mg/day. Fifteen patients (51.7%) were subsequently escalated to 4 mg/day and 4 (13.8%) to 5 mg/day. Only four (13.8%) patients discontinued treatment due to adverse events (AEs). The median PFS was 3.8 months (95% CI, 2.7-4.9), and the median OS was 7.6 months (95% CI, 6.5-8.7). Treatment-related adverse events (TRAEs) were observed in all 29 patients (100%). The most frequently occurring (>10%) TRAEs greater than Grade 3 were HFSR (20.7%), hypertension (20.7%), and diarrhea (10.3%).

CONCLUSION: Our study indicated that a dose of 4 mg/day was well tolerated by most elderly patients, suggesting that fruquintinib dose-escalation strategy during the first cycle could serve as a viable alternative to the standard 5 mg/day dosing.

PMID:38063405 | DOI:10.1002/cam4.6786

Inn Med (Heidelb). 2023 Dec 7. doi: 10.1007/s00108-023-01630-x. Online ahead of print.

ABSTRACT

If the individual diagnoses of older people with multimorbidity are treated according to guidelines and by different specialists, confusing medication plans are sometimes the consequence. Therefore, a regular and structured drug evaluation is essential. As the life goals of patients can be very different, especially in older age, certain preliminary considerations should be made when starting, prescribing or discontinuing medication, taking into account the individual situation, including geriatric aspects. Updated so-called positive and negative lists provide assistance as to which medications are suitable or unsuitable for older people. Discontinuing certain medications when the life expectancy is reduced certainly makes sense but undertreatment of symptoms that cause distress to people, such as pain, should definitely be avoided.

PMID:38059997 | DOI:10.1007/s00108-023-01630-x

Eur J Clin Pharmacol. 2023 Dec 7. doi: 10.1007/s00228-023-03592-3. Online ahead of print.

ABSTRACT

PURPOSE: Selective androgen receptor modulators (SARMs) have demonstrated agonist activity on the androgen receptor in various tissues, stimulating muscle mass growth and improving bone reconstruction. Despite being in clinical trials, none has been approved by the Food and Drug Administration (FDA) or European Medicines Agency for pharmacotherapy. Still, SARMs are very popular as performance-enhancing drugs. The FDA has issued warnings about the health risks associated with SARMs, but the long-term exposure and possible adverse events still need to be fully understood. This review aims to evaluate the adverse events associated with using SARMs by humans.

METHODS: PubMed database was searched from September 16, 2022, to October 2, 2023. In total, 20 records were included in the final review. Data from preclinical and clinical studies supported the review.

RESULTS: Since 2020, 20 reports of adverse events, most described as drug-induced liver injury associated with the use of SARM agonists, have been published. The main symptoms mentioned were cholestatic or hepatocellular liver injury and jaundice. Limited data are related to the dosages and purity of SARM supplements.

CONCLUSION: Promoting SARMs as an anabolic agent in combination with other performance-enhancing drugs poses a risk to users not only due to doping controls but also to health safety. The lack of quality control of consumed supplements makes it very difficult to assess the direct impact of SARMs on the liver and their potential hepatotoxic effects. Therefore, more detailed analyses are needed to determine the safety of using SARMs.

PMID:38059982 | DOI:10.1007/s00228-023-03592-3

Bioessays. 2023 Dec 7:e2300117. doi: 10.1002/bies.202300117. Online ahead of print.

ABSTRACT

Bisphosphonates are a class of drugs which have shown good efficacy in the treatment of post-menopausal osteoporosis, as well as a good safety profile. However, side-effects such as risk for atypical femoral fractures (AFF) have appeared, leading to a decline in use of the drugs by many patients who would benefit from the treatment. While patient characteristics have contributed to improved understanding of risk factors, the mechanisms involved that explain AFF risk have not appeared. Recently, the possibility that the mechanism(s) involved drug-induced modification of cells of the nutrient canals of the femur and subsequent compromise in the bone matrix has been published. The present Hypothesis article builds on the concept presented earlier and expands into biomechanical considerations. An analogy of the mechanisms involved to a real-life scenario is also presented. While this analogy has limitations, consideration of the biomechanical implications of progressive alterations to defects presented by compromised nutrient canal-bone matrix also presents potential relationships with AFF risk.

PMID:38059881 | DOI:10.1002/bies.202300117

ANZ J Surg. 2023 Dec 7. doi: 10.1111/ans.18812. Online ahead of print.

ABSTRACT

BACKGROUND: In recent years, certain body composition measures, assessed by computed tomography (CT), have been found to be associated with chemotherapy toxicities. This review aims to explore available data on the relationship between skeletal muscle and adiposity, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intramuscular and intermuscular adipose tissue and their association with chemotherapy toxicity in non-metastatic colorectal cancer (CRC) patients.

METHODS: A systematic literature search following PRISMA guidelines was conducted in Medline, Embase, Cochrane and Web of Science, for papers published between 2011 and 2023. The search strategy combined keywords and MESH terms relevant to 'body composition', 'chemotherapy toxicities', and 'non-metastatic colorectal cancer'.

RESULTS: Out of 3868 studies identified, six retrospective studies fulfilled the inclusion criteria with 1024 eligible patients. Low skeletal muscle mass was strongly associated with increased incidence of both chemotherapy toxicities and dose-limiting toxicity (DLT). The association of VAT, intramuscular and intermuscular adiposity was heterogeneous and inconclusive. There was no association between SAT and chemotherapy intolerance. No universal definitions or cut-offs for sarcopenia and obesity were noted. All studies utilized 2-dimensional (2D) CT slices for CT body composition assessment with varied selection on the vertebral landmark and inconsistent reporting of tissue-defining Hounsfield unit (HU) measurements.

CONCLUSION: Low skeletal muscle is associated with chemotherapy toxicities in non-metastatic CRC. However, quality evidence on the role of adiposity is limited and heterogeneous. More studies are needed to confirm these associations with an emphasis on a more coherent body composition definition and an approach to its assessment, especially regarding sarcopenia.

PMID:38059530 | DOI:10.1111/ans.18812

Case Rep Ophthalmol. 2023 Dec 5;14(1):673-678. doi: 10.1159/000535077. eCollection 2023 Jan-Dec.

ABSTRACT

INTRODUCTION: With the increasing use of immune checkpoint inhibitors, ocular adverse events have gained attention. We describe a case of atypical keratitis presumably induced by atezolizumab, a programmed cell death ligand 1 inhibitor.

CASE PRESENTATION: A 73-year-old Japanese woman developed ring-shaped marginal infiltrations with epithelial breakdown of the corneas in both eyes. The patient had advanced small cell lung cancer and had received intravenous carboplatin, etoposide, and atezolizumab. She was treated with topical administration of 0.1% sodium phosphate betamethasone and 0.5% moxifloxacin six times daily. On day 14 following initial presentation, marked reduction of bilateral corneal infiltration was observed. During the succeeding cycles of chemotherapy, marginal keratitis did not recur, and then, the topical steroid was gradually tapered.

CONCLUSIONS: Cancer immunotherapy, including atezolizumab, may lead to active T-cell recruitment into the cornea, which result in autoimmune corneal keratitis. We believe that this report is informative to both ophthalmologists and oncologists involved in the treatment of patients receiving cancer immunotherapy.

PMID:38058358 | PMC:PMC10697742 | DOI:10.1159/000535077

Clin Nutr ESPEN. 2023 Dec;58:152-159. doi: 10.1016/j.clnesp.2023.09.919. Epub 2023 Sep 24.

ABSTRACT

BACKGROUND & AIMS: The concurrent use of herbal and dietary supplements and conventional drugs can lead to interactions in patients with cancer, of which hepatotoxicity is one of the most concerning sequelae. This study examined the potential supplement-drug interactions involving the hepatic system, and their associations with documented liver diseases, among patients with cancer in a large population-based cohort in the UK Biobank.

METHODS: Participants diagnosed with cancer and had completed supplement-use assessment after diagnosis were included. Potentially interacting supplement-drug combinations that involved CYP enzymes or increased the risk of hepatotoxicity were identified from four tertiary databases. Liver diseases were identified using ICD-codes K70-77. Log-binomial regression was used to investigate the associations between potentially-interacting supplement-drug combinations and liver diseases documented (1) at any time, and (2) confined to only after the time of supplement-use assessment, adjusting for age, sex and pre-existing comorbidities.

RESULTS: This analysis included 30,239 participants (mean age = 60.0 years; 61.9% female). Over half (n = 17,698, 58.5%) reported the use of supplements after cancer diagnoses. Among supplements users, 36.9% (n = 6537/17,698) were on supplement-drug combinations with interacting potential involving the hepatic system. Patients taking supplements and drugs who had hepatic comorbidities were more likely to take potentially interacting pairs (adjusted risk ratio = 1.14, 95% CI = 1.06-1.23, p < 0.001). However, no significant association was observed between the use of these combinations and subsequent liver diseases (all p > 0.05).

CONCLUSION: Approximately one-third of the participants who had cancer and were supplement users had a risk of potential supplement-drug interactions that contribute to adverse liver effect. Healthcare professionals should communicate with patients with cancer, especially those with pre-existing liver diseases, about supplement use and proactively assess the clinical significance of potential interactions.

PMID:38057000 | DOI:10.1016/j.clnesp.2023.09.919

J Med Syst. 2023 Dec 6;48(1):2. doi: 10.1007/s10916-023-02008-0.

ABSTRACT

The development of health information technology available and accessible to professionals is increasing in the last few years. However, a low number of electronic health tools included some kind of information about medication reconciliation. To identify all the electronic medication reconciliation tools aimed at healthcare professionals and summarize their main features, availability, and clinical impact on patient safety. A systematic review of studies that included a description of an electronic medication reconciliation tool (web-based or mobile app) aimed at healthcare professionals was conducted. The review protocol was registered with PROSPERO: registration number CRD42022366662, and followed PRISMA guidelines. The literature search was performed using four healthcare databases: PubMed, EMBASE, Cochrane Library, and Scopus with no language or publication date restrictions. We identified a total of 1227 articles, of which only 12 met the inclusion criteria.Through these articles,12 electronic tools were detected. Viewing and comparing different medication lists and grouping medications into multiple categories were some of the more recurring features of the tools. With respect to the clinical impact on patient safety, a reduction in adverse drug events or medication discrepancies was detected in up to four tools, but no significant differences in emergency room visits or hospital readmissions were found. 12 e-MedRec tools aimed at health professionals have been developed to date but none was designed as a mobile app. The main features that healthcare professionals requested to be included in e-MedRec tools were interoperability, "user-friendly" information, and integration with the ordering process.

PMID:38055124 | DOI:10.1007/s10916-023-02008-0

Int J Drug Policy. 2023 Dec 4;123:104258. doi: 10.1016/j.drugpo.2023.104258. Online ahead of print.

ABSTRACT

INTRODUCTION: Drug use and trading are typically social activities; however, supply through cryptomarkets can occur without any in-person social contact. People who use drugs alone may be at higher risk of experiencing harms, for example, due to lack of others who may call for emergency assistance. Alternatively, cryptomarkets may be a source of harm reduction information and drugs with better-known content and dose, potentially reducing the risk of adverse events. This study examines relationships between cryptomarket use, drug-using social networks and adverse drug events for MDMA, cocaine and LSD.

METHOD: A subsample of 23,053 respondents from over 70 countries was collected in the 2018 Global Drug Survey. People who reported using MDMA, cocaine or LSD were asked about using cryptomarkets to purchase these drugs; any adverse drug events requiring medical treatment (combining seeking treatment and should have sought treatment but did not); and social networks who they had used the specific drug with. All measures referred to the last 12 months, hereon referred to as 'recent'. Binary logistic regressions examined relationships between cryptomarket use, drug-using social networks, and adverse drug events, controlling for age, gender, and frequency of drug use.

RESULTS: Adverse events from any drug type were low (5.2%) and for each drug; MDMA (3.5%); cocaine (3.3%); and LSD (3.5%). After controlling for covariates, recent cryptomarket use was associated with increased likelihood of having no drug-using network for each drug type. People who recently used cryptomarkets were more likely to report adverse cocaine (AOR = 1.70 (1.22-2.37)) and LSD (AOR = 1.58 (1.12-2.09)) events. For those reporting a network size >1, network characteristics did not differ with recent cryptomarket use; however, those reporting recent cryptomarket use were more likely to report adverse LSD events (AOR = 1.86 (0.99-3.51)).

CONCLUSION: People who reported purchasing drugs from cryptomarkets more commonly reported having no drug-using network, and cryptomarket purchase was associated with reported adverse events. Our results support the notion that cryptomarket use increases drug-related harm, but further disentanglement of multiple complex mechanisms is needed in future research.

PMID:38056221 | DOI:10.1016/j.drugpo.2023.104258

Cureus. 2023 Nov 4;15(11):e48272. doi: 10.7759/cureus.48272. eCollection 2023 Nov.

ABSTRACT

Background Caudal epidural anesthesia technique is a relevant method for postoperative analgesia in newborns, allowing for the reduction of drug-induced respiratory depression. The threading of a catheter is, however, uncommon in clinical practice. Our main purpose was to describe our experience regarding caudally inserted epidural catheters in neonates undergoing major abdominal surgery. Methods We included every full-term neonate undergoing surgery under combined caudal epidural-general anesthesia from 2017 to 2022 in our institution. After induction of general anesthesia, an ultrasound-guided caudal epidural injection was performed, and an epidural catheter was inserted for perioperative analgesia. An epidural bolus of ropivacaine was administered to every patient before the surgical incision, and an epidural infusion of ropivacaine 0.05% was administered for 24 hours. Results Retrospectively obtained data included six full-term neonates with American Society of Anesthesiologists (ASA) physical status II to IV. Intraoperatively, good analgesia was achieved without hemodynamic instability or need for additional systemic opioids after induction. At the end of surgery, five of the six neonates were extubated without adverse respiratory events. Postoperatively, effective analgesia was achieved in four cases with an epidural infusion of ropivacaine 0.05%, at a rate between 0.2 and 0.4 mg/kg/h, and intravenous paracetamol. Epidural pain control was not successful in one neonate, and thus an intravenous fentanyl infusion was added. The sixth neonate remained intubated for prolonged mechanical ventilation due to surgical complications, and thus an intravenous fentanyl infusion was introduced for sedation in the neonatal intensive care unit (NICU), not allowing to evaluate the effectiveness of the epidural infusion alone. No other complications related to the epidural catheters were reported. Conclusion Continuous caudal epidural analgesia may be a valuable technique with a low risk of complications, decreasing the incidence of respiratory adverse events in this patient population. Although more cases are needed for a stronger conclusion, it has become a useful analgesic strategy for major abdominal surgery in neonates in our institution.

PMID:38054162 | PMC:PMC10695668 | DOI:10.7759/cureus.48272

J Drugs Dermatol. 2023 Dec 1;22(12):e42-e43. doi: 10.36849/JDD.6532.

ABSTRACT

Actemra (tocilizumab) received emergency use authorization for the treatment of coronavirus disease 2019 (COVID-19) in June 2021. Literature has linked numerous cutaneous adverse effects to tocilizumab. In this current survey, investigators reviewed and compared these adverse effects to the common cutaneous manifestations of COVID-19. While similarities in patient presentation exist, important distinctions are made to aid dermatologists in their clinical diagnosis. &nbsp;J Drugs Dermatol. 2023;22(12):e42-e43.&nbsp; &nbsp;&nbsp; doi:10.36849/JDD.6532e.

PMID:38051828 | DOI:10.36849/JDD.6532

Clin Infect Dis. 2023 Dec 5;77(Supplement_6):S487-S496. doi: 10.1093/cid/ciad642.

ABSTRACT

Live biotherapeutic products (LBPs) represent a new class of therapeutics indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in adults. However, microbiota-based therapies have been used in CDI management before the Food and Drug Administration (FDA) designated this new drug class. The regulation of these microbiome-based therapies has varied, and several safety concerns have arisen over time. Requirements established by the FDA regarding the development of LBPs minimizes many of these prior concerns, and phase III trials have proven the safety and efficacy of 2 stool donor-derived LBPs: fecal microbiota, live-jslm (Rebyota™; formerly RBX2660) and fecal microbiota spores, live-brpk (Vowst™; formerly SER-109). Mild gastrointestinal side effects are common, but no severe drug-related adverse events have been reported with their use to date. A third LBP entering phase III clinical trials, VE303, follows a novel approach by sourcing bacterial strains from clonal cell banks and has demonstrated a similarly favorable safety profile.

PMID:38051970 | DOI:10.1093/cid/ciad642

Clin Ophthalmol. 2023 Nov 29;17:3645-3653. doi: 10.2147/OPTH.S439255. eCollection 2023.

ABSTRACT

PURPOSE: Clinically, glaucoma is a serious problem because it is asymptomatic until a relatively late stage in most cases, which can lead to delays in the diagnosis and treatment of the disease. The purpose of this study was to clarify the rank-order of the association of glaucoma with the causative drugs using a spontaneous reporting system database.

METHODS: Data were extracted from the Japanese Adverse Drug Event Report database of the Pharmaceuticals and Medical Devices Agency (Japan). Based on reports of glaucoma caused by all drugs, we calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) for glaucoma.

RESULTS: Among 609 reports of adverse events corresponding to glaucoma (46%, women), the most frequently implicated drug were steroids (prednisolone, betamethasone sodium phosphate, triamcinolone acetonide, and fluorometholone), pregabalin, ranibizumab, crizotinib, tacrolimus hydrate, darbepoetin alfa, and foscarnet sodium hydrate. Among 207 reports involved in angle-closure glaucoma (86%, women), anticholinergic drug and antidepressants ranked high and showed signals. Signals were also detected in bromazepam (ROR, 69.7; 95% CI, 30.9-157.5), oral brotizolam (ROR, 16.6; 95% CI, 6.18-44.8), and oral milnacipran hydrochloride (ROR, 22.8; 95% CI, 8.46-61.4) for angle-closure glaucoma.

CONCLUSION: A national pharmacovigilance database enabled us to identify the drugs that frequently induce glaucoma. The likelihood of the reporting of glaucoma varied among the drugs, which should be used carefully in clinical practice to avoid it.

PMID:38050555 | PMC:PMC10693769 | DOI:10.2147/OPTH.S439255

Pharmacotherapy. 2023 Dec 4. doi: 10.1002/phar.2898. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Failure of initial benzodiazepine therapy in patients with status epilepticus warrants urgent administration of a second-line antiseizure medication. Recent studies suggest rapid administration of high-dose, undiluted levetiracetam is safe in adults; however, no information exists in pediatric patients. The purpose of this study was to evaluate the safety and tolerability of undiluted levetiracetam at a pediatric institution.

METHODS: Retrospective, single-center, cohort analysis of patients who received high-dose >60 mg/kg (-10%) up to 4500 mg diluted or undiluted intravenous levetiracetam between May 6, 2020 to July 31, 2022 at a large pediatric academic medical center. The primary outcome was the assessment of hemodynamic disturbances (bradycardia, hypotension) and/or infusion-related reactions after administration of the levetiracetam infusion.

RESULTS: A total of 776 levetiracetam doses were included, 358 doses administered and 418 doses wasted. The doses administered (61 undiluted and 297 diluted) accounted for a total of 252 patients (39 received undiluted and 213 received diluted levetiracetam) (median [minimum-maximum range] age, 2 y [1 d-32.7 y]; mean (standard deviation [SD]) weight, 20.1 kg (22.1 kg)). The incidence of hemodynamic disturbances and infusion-related reactions was not statistically significant between diluted and undiluted groups (p= 0.87). The median (interquartile range [IQR]) time difference between first-line antiseizure medication and levetiracetam administration in patients with status epilepticus was 18 minutes (10.5-30.5) in the undiluted group versus 36.5 minutes (21.8-67.3) in the diluted group; p<0.01. Additionally, there was a significant amount of drug waste from dispensed but not administered doses of the diluted bag compared to undiluted vials (57.6% diluted versus 18.7% undiluted, p<0.001).

CONCLUSION: Undiluted levetiracetam was not associated with an increased incidence of adverse effects compared to diluted levetiracetam in high-doses, up to 4500 mg given over 5 minutes in pediatric patients.

PMID:38050327 | DOI:10.1002/phar.2898

Reg Anesth Pain Med. 2023 Nov 30:rapm-2023-104941. doi: 10.1136/rapm-2023-104941. Online ahead of print.

ABSTRACT

BACKGROUND/IMPORTANCE: Arachnoiditis is a rare but devastating disorder caused by various insults, one of which is purported to be local anesthetic neurotoxicity following neuraxial blockade. However, the relationship between local anesthetics administered into the neuraxis and the development of arachnoiditis has not been clearly elucidated.

OBJECTIVE: We aimed to summarize the existing complex body of literature and characterize both the essential features and strength of any association between neuraxial local anesthetic neurotoxicity and arachnoiditis with a view toward mitigating risk, enhancing prevention, and refining informed consent discussions.

EVIDENCE REVIEW: We reviewed all published reports of arachnoiditis attributed to local anesthetic neurotoxicity following perioperative neuraxial anesthesia. This narrative review was based on a systematic search methodology, which included articles published up until December 2022.

FINDINGS: Thirty-eight articles were included, comprising 130 patients, over one-half of which were published prior to this century and inconsistent with modern practice. Neuraxial techniques included 78 epidurals, 48 spinals, and 5 combined spinal-epidurals, mostly for obstetrics. Reporting of essential procedural data was generally incomplete. Overall, at least 57% of patients experienced complicated needle/catheter insertion, including paresthesia, pain, or multiple attempts, irrespective of technique. The onset of neurological symptoms ranged from immediate to 8 years after neuraxial blockade, while the pathophysiology of arachnoiditis, if described, was heterogeneous.

CONCLUSIONS: The existing literature attributing arachnoiditis to local anesthetic neurotoxicity is largely outdated, incomplete, and/or confounded by other potential causes, and thus insufficient to characterize the features and strength of any association.

PMID:38050164 | DOI:10.1136/rapm-2023-104941

Drug Ther Bull. 2023 Dec 2:dtb-2023-000063. doi: 10.1136/dtb.2023.000063. Online ahead of print.

NO ABSTRACT

PMID:38050092 | DOI:10.1136/dtb.2023.000063

Drug Ther Bull. 2023 Nov 24:dtb-2023-000064. doi: 10.1136/dtb.2023.000064. Online ahead of print.

NO ABSTRACT

PMID:38050011 | DOI:10.1136/dtb.2023.000064

Sci Rep. 2023 Dec 4;13(1):21365. doi: 10.1038/s41598-023-46909-z.

ABSTRACT

As demand for renewable energy is rising, wind power development is rapidly growing worldwide. In its wake, conflicts arise over land use changes converting pristine nature into industrial power plants and its associated adverse biodiversity effects, crowned by one of the most obvious and deadly consequences: bird collisions. Most post-construction studies report low levels of avian mortality, but the majority of these studies are conducted primarily on larger birds. However, the diversity and abundance of small passerine birds are rarely reflected in the carcass surveys, although they in numeric proportion to their abundances should be the most numerous. The assumption that surveys find all carcasses seems thus rarely fulfilled and passerine mortality is likely to be grossly underestimated. We therefore designed an experiment with dummy birds to estimate mortality of small-bodied passerines and other small-bodied birds during post-construction surveys, tested in a medium-sized wind farm in western Norway. The wind farm was surveyed weekly during the migration periods by carcass survey teams using trained dogs to find killed birds. The dogs in the carcass surveys were more successful in locating the large than the small dummy birds (60-200 g), where they found 74% of the large dummy birds. Detecting the smaller category (5-24 g) was more demanding and the dogs only found 17% of the small dummy birds. Correcting the post-construction carcass survey outcome with the results from the experiment leads to an almost fourfold increase in estimated mortality rates, largely due to the low detection rate of the smallest category. The detection rates will naturally vary between wind farms, depending on the specific habitat characteristics, the efficiency of the carcass surveys and the search intervals. Thus, implementing a simple experiment with dummy birds to future post-construction surveys will produce more accurate estimates of the wind turbine mortality rates, and thus improve our understanding of the biodiversity effects of conforming to a more sustainable future.

PMID:38049460 | PMC:PMC10695956 | DOI:10.1038/s41598-023-46909-z