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{"title":"Neurodevelopment at 10 months and 2–3 years old after early and prolonged anaesthesia in infancy: General Anaesthesia & Brain Activity study (GABA) secondary analysis","authors":"Laura Cornelissen ,&nbsp;Siobhan Coffman ,&nbsp;Isabelle Kim ,&nbsp;Ellen Underwood ,&nbsp;Alice Tao ,&nbsp;Maria G. Maloney ,&nbsp;Carolina Donado ,&nbsp;Kimberly Lobo ,&nbsp;Charles A. Nelson ,&nbsp;Takao K. Hensch ,&nbsp;Laurel J. Gabard-Durnam ,&nbsp;Charles B. Berde","doi":"10.1016/j.bjao.2025.100383","DOIUrl":"10.1016/j.bjao.2025.100383","url":null,"abstract":"<div><h3>Background</h3><div>Effects of early and prolonged exposure to general anaesthesia on the developing brain are unclear. The study objective was to examine developmental outcomes at 10 months and 2–3 yr of age after general anaesthesia planned for &gt;2 h in the first 2 months of life.</div></div><div><h3>Methods</h3><div>This is a secondary analysis of the General Anaesthesia &amp; Brain Activity (GABA) study—a prospective, single-centre, longitudinal observational study. The final dataset included 59 children who were unexposed and 31 children who were exposed to early prolonged general anaesthesia who completed the primary outcome measure, Bayley Scales of Infant and Toddler Development-III (BSID) assessments at 10 months, at 2–3 yr old, or both. Analyses used adjusted Welch's <em>t</em>-tests, linear regression, and linear mixed effects models.</div></div><div><h3>Results</h3><div>BSID composite scores for cognition were similar between general anaesthesia and unexposed cohorts at 10 months (<em>P</em>_adj=0.566, standardised mean difference [SMD]=0.27) and at 2–3 yr (<em>P</em>_adj=0.651, SMD=0.25). Motor and language scores were similar between cohorts at 10 months (motor: <em>P</em>_adj=1, SMD=0.13; language: <em>P</em>_adj=0.806, SMD=0.19) and fell within typical reference ranges. Linear regression analysis found no association between BSID cognition scores and cumulative hours of general anaesthesia at 10 months (<em>R</em>=0.06, <em>P</em>=0.635) or at 2–3 yr (<em>R</em>=−0.13, <em>P</em>=0.293).</div></div><div><h3>Conclusions</h3><div>Children with early prolonged general anaesthesia showed BSID scores comparable to age-matched controls. This analysis provides additional preliminary support for the safety of general anaesthesia on the developing brain even when general anaesthesia is prolonged, repeated, or administered very early in life.</div></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":"14 ","pages":"Article 100383"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143579222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postoperative acute kidney injury is associated with persistent renal dysfunction: a multicentre propensity-matched cohort study","authors":"Blaine Stannard ,&nbsp;Richard H. Epstein ,&nbsp;Eilon Gabel ,&nbsp;Girish N. Nadkarni ,&nbsp;Yuxia Ouyang ,&nbsp;Hung-Mo Lin ,&nbsp;Valiollah Salari ,&nbsp;Ira S. Hofer","doi":"10.1016/j.bjao.2025.100384","DOIUrl":"10.1016/j.bjao.2025.100384","url":null,"abstract":"<div><h3>Background</h3><div>The risk of developing a persistent reduction in renal function after postoperative acute kidney injury (pAKI) is not well established. The goal of this investigation was to evaluate whether patients who develop pAKI have a greater decline in long-term renal function than patients who do not.</div></div><div><h3>Methods</h3><div>In this multicentre retrospective propensity-matched study, anaesthesia data warehouses at three tertiary care hospitals were queried. Adult patients undergoing surgery with available preoperative and postoperative creatinine results and without baseline haemodialysis requirements were included. Patients were stratified by occurrence of pAKI as defined by the Acute Kidney Injury Network classification. The primary outcome was a decline in follow-up glomerular filtration rate (GFR) of 40% relative to baseline, based on follow-up outpatient visits from 0 to 36 months after hospital discharge. A propensity score-matched sample was used in Kaplan–Meier analysis and a piecewise Cox model to compare the time to reach a 40% decline in GFR for patients with and without pAKI.</div></div><div><h3>Results</h3><div>In 95 213 patients, the rate of pAKI ranged from 9.9% to 13.7%. In the piecewise Cox model, pAKI was associated with a significantly increased hazard of a 40% decline in GFR. The common-effect hazard ratio was 13.35 (95% confidence interval [CI] 10.79–16.51, <em>P</em>&lt;0.001) for 0–6 months, 7.07 (5.52–9.05, <em>P</em>&lt;0.001) for 6–12 months, 6.02 (4.69–7.74, <em>P</em>&lt;0.001) for 12–24 months, and 4.32 (2.65–7.05, <em>P</em>&lt;0.001) for 24–36 months.</div></div><div><h3>Conclusions</h3><div>pAKI is associated with a significantly increased hazard of a 40% decline in GFR up to 36 months after surgery across three institutions.</div></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":"14 ","pages":"Article 100384"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between elevated preoperative red cell distribution width and worsening kidney function after noncardiac operation. A propensity score and competing risk weighted retrospective cohort study","authors":"Halldór B. Olafsson ,&nbsp;Sigurbergur Karason ,&nbsp;Magnus K. Magnusson ,&nbsp;Olafur S. Indridason ,&nbsp;Thorir E. Long ,&nbsp;Martin I. Sigurðsson","doi":"10.1016/j.bjao.2025.100380","DOIUrl":"10.1016/j.bjao.2025.100380","url":null,"abstract":"<div><h3>Background</h3><div>Elevated red cell distribution width (RDW) is associated with increased postoperative mortality, but less is known about kidney outcomes. This study investigated the association between elevated preoperative RDW and postoperative worsening of long-term kidney function and incidence of acute kidney injury.</div></div><div><h3>Methods</h3><div>This retrospective cohort study included patients ≥18 yr undergoing noncardiac operation at Landspitali—The National University Hospital of Iceland between 2005 and 2018. Outcomes were compared between groups with elevated preoperative RDW (13.3–14.0%, 14.0–14.7%, 14.7–15.8%) and a propensity score-matched cohort (RDW ≤13.3%) using Fine–Gray competing risk regression analysis, with death as a competing event. The primary outcome was time to worsening of at least one estimated glomerular filtration rate (eGFR) category sustained for 3 months. Secondary outcomes were acute kidney injury, length of hospital stay, and 30-day readmission rate.</div></div><div><h3>Results</h3><div>Out of 63 056 operations included in this study, 55 724 were available for propensity score-matched analysis. The hazard of long-term eGFR worsening was higher for patients with RDW between 14.0% and 14.7%: hazard ratio (HR) 1.23 (95% confidence interval [CI] 1.13–1.35), 14.7% and 15.8%: HR 1.20 (95% CI 1.07–1.34), and &gt;15.8%: HR 1.16 (95% CI 1.00–1.34) compared with matched controls (RDW &lt;13.3%), adjusted for death as a competing event. For secondary outcomes there was no difference in acute kidney injury, but increased risk of readmission for patients with RDW of 14.0–14.7% (9.8% <em>vs</em> 8.5%, <em>P</em>=0.01), 14.7–15.8% (12.2% <em>vs</em> 10.1%, <em>P</em>=0.001), and &gt;15.8% (14.9% <em>vs</em> 11.4%, <em>P</em>&lt;0.001).</div></div><div><h3>Conclusions</h3><div>Elevated preoperative RDW was associated with long-term worsening of eGFR category after operation.</div></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":"13 ","pages":"Article 100380"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Premedication with intranasal dexmedetomidine in patients undergoing total knee arthroplasty under spinal anaesthesia (TKADEX)—a prospective, double-blinded, randomised controlled trial","authors":"Suvi-Maria Tiainen ,&nbsp;Heta Heinonen ,&nbsp;Atte Koskinen ,&nbsp;Sanna Mäkelä ,&nbsp;Ruut Laitio ,&nbsp;Eliisa Löyttyniemi ,&nbsp;Keijo Mäkelä ,&nbsp;Teijo I. Saari ,&nbsp;Panu Uusalo","doi":"10.1016/j.bjao.2025.100382","DOIUrl":"10.1016/j.bjao.2025.100382","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies have shown that perioperative use of adjuvants, such as the alpha-2 agonist dexmedetomidine, may reduce postoperative pain and opioid requirements. However, information about optimal dosing is lacking. We investigated if premedication with intranasal dexmedetomidine compared with placebo reduces postoperative pain in patients undergoing total knee arthroplasty under spinal anaesthesia.</div></div><div><h3>Methods</h3><div>This single-centre, double-blind, two-arm study compared premedication with intranasal dexmedetomidine (single 1 μg kg⁻¹ dose) to intranasal saline in 101 consecutive elective patients undergoing total knee arthroplasty under spinal anaesthesia. The primary outcome was postoperative pain measured with the numerical rating scale during the first 24 h. Secondary outcomes were postoperative opioid requirement, perioperative haemodynamic variables, requirement of additional intraoperative sedation, incidence of postoperative nausea and vomiting, and patient satisfaction at 30 days after surgery.</div></div><div><h3>Results</h3><div>Patients in the dexmedetomidine group had lower numerical rating scale scores [median (interquartile range) 2.0 (0.0–3.0)] at 3 h when compared with the control group [3.0 (2.0–4.0)] (<em>P</em>=0.037). Cumulative 24 h opioid requirements (in morphine equivalents) did not differ between dexmedetomidine [45 mg (30–68 mg)] and control groups [53 mg (38–88 mg)] (<em>P</em>=0.334). More patients in the dexmedetomidine group were satisfied with pain management in the ward (<em>P</em>=0.0013). The groups did not differ in the incidence of postoperative nausea and vomiting (<em>P</em>=0.310) or haemodynamic adverse events (<em>P</em>&gt;0.27 for all).</div></div><div><h3>Conclusions</h3><div>Our results indicate that intranasal dexmedetomidine may reduce postoperative pain and the requirement for additional sedation and increase short-term patient satisfaction in patients undergoing total knee arthroplasty.</div></div><div><h3>Clinical trial registration</h3><div>ClinicalTrials.gov (NCT 04859283).</div></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":"13 ","pages":"Article 100382"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted heart rate control using the funny current inhibitor ivabradine to reduce morbidity in patients undergoing noncardiac surgery: study protocol for a phase 2a, triple-blind, placebo-controlled randomised trial","authors":"Bernardo Bollen Pinto ,&nbsp;Benjamin Shelley ,&nbsp;Priyanthi Dias ,&nbsp;Salma Begum ,&nbsp;Florence Ennahdi-Elidrissi ,&nbsp;Tom E.F. Abbott ,&nbsp;Russell Hewson ,&nbsp;Akshaykumar Patel ,&nbsp;Kamran Khan ,&nbsp;Rupert M. Pearse ,&nbsp;Gareth L. Ackland","doi":"10.1016/j.bjao.2025.100378","DOIUrl":"10.1016/j.bjao.2025.100378","url":null,"abstract":"<div><h3>Background</h3><div>Myocardial injury is strongly associated with excess morbidity and mortality after noncardiac surgery. Higher heart rate may result in perioperative myocardial injury through demand–supply mismatch. Alternatively, higher heart rates may reflect autonomic dysfunction that promotes myocardial injury independently of heart rate. The specific hyperpolarisation-activated, cyclic nucleotide-gated (HCN)-4 (funny) channel inhibitor ivabradine slows the heart rate without altering autonomic control, blood pressure, or myocardial contractility. We hypothesise that individuals with autonomic dysfunction may benefit most from ivabradine reducing heart rate control to minimise myocardial injury-associated morbidity.</div></div><div><h3>Methods</h3><div>This triple-blind, international, multicentre, randomised, placebo-controlled, parallel group randomised trial will recruit 350 patients, aged ≥55 yr, with cardiovascular risk factors for myocardial injury during elective noncardiac surgery. To achieve the target heart rate &lt;70 beats min⁻¹ (sinus rhythm), patients will be randomly allocated in a 1:1 ratio using minimisation and will receive either ivabradine (2.5–7.5 mg) or placebo tablet twice daily, from the morning of surgery for 72 h. High-sensitivity troponin T concentrations will be measured before and up to 72 h after surgery, blinded to participants, clinicians, and investigators. The primary outcome is myocardial injury associated with morbidity within 7 days of randomisation (defined by Postoperative Morbidity Survey). Secondary outcomes include peak troponin concentrations, complications within 30 days, and mortality within 6 months of surgery. Pre-specified analyses will include resting and orthostatic heart rate plus N-terminal prohormone of brain natriuretic peptide concentrations before surgery.</div></div><div><h3>Conclusions</h3><div>This phase 2b study will explore whether targeted heart rate control reduces morbidity after surgery, using ivabradine to selectively slow the heart rate without altering perioperative autonomic control.</div></div><div><h3>Clinical trial registration</h3><div>ISRCTN12903789.</div></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":"13 ","pages":"Article 100378"},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143446095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frameworks for the design and reporting of anaesthesia interventions in perioperative clinical trials","authors":"Karen D. Coulman ,&nbsp;Lucy Elliott ,&nbsp;Natalie S. Blencowe ,&nbsp;Joyce Yeung ,&nbsp;Leila Rooshenas ,&nbsp;Robert J. Hinchliffe ,&nbsp;Ronelle Mouton","doi":"10.1016/j.bjao.2024.100374","DOIUrl":"10.1016/j.bjao.2024.100374","url":null,"abstract":"<div><h3>Background</h3><div>Interventions from RCTs can only be replicated and implemented if reported in sufficient detail. This study developed frameworks to assist researchers with describing, monitoring, and reporting the key components of anaesthetic interventions in trials.</div></div><div><h3>Methods</h3><div>This study comprised three phases: (1) initial framework development—text describing the delivery of anaesthetic interventions was coded and categorised into components using thematic analysis; (2) refinement of frameworks—facilitated structured group discussions were conducted with perioperative clinicians, researchers, and journal editors to elicit additional framework categories and consider clarity and feasibility; (3) framework testing and further refinement—cognitive interviews with professionals undertaking trials evaluating anaesthesia interventions to test the feasibility of using the frameworks in contemporary perioperative trials.</div></div><div><h3>Results</h3><div>Three frameworks were developed for general, regional, and sedation anaesthesia interventions. Data saturation of categories within the frameworks was reached after inclusion of 15 RCTs for general and regional anaesthesia, and 13 for sedation. Each framework is structured into three main sections: (1) professional(s) delivering the intervention; (2) setting; and (3) intervention components, with descriptions of the preoperative, intraoperative, and postoperative stages unique to each anaesthetic intervention. Each framework deconstructs an anaesthetic intervention into component parts to support researchers with the design and reporting of RCTs. Final frameworks are available at: <span><span>https://anaesthesiaframeworks.blogs.bristol.ac.uk/</span><svg><path></path></svg></span>.</div></div><div><h3>Conclusions</h3><div>We provide novel frameworks to be used during the design of perioperative trials to facilitate the design, delivery, and reporting of anaesthesia interventions.</div></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":"13 ","pages":"Article 100374"},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143151350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripherally inserted central catheters versus implanted port catheters in patients with breast cancer: a post hoc analysis of the PICCPORT randomised controlled trial","authors":"Anton Utas ,&nbsp;Stefanie Seifert ,&nbsp;Knut Taxbro","doi":"10.1016/j.bjao.2025.100377","DOIUrl":"10.1016/j.bjao.2025.100377","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer is the most prevalent malignancy affecting women. However, the optimal strategy for patients requiring long-term central venous catheters in breast cancer treatment remains uncertain. Previous investigations involving a mixed cancer population have shown a higher frequency of adverse events among patients receiving peripherally implanted central catheters (PICCs) compared with totally implanted central catheters (PORTs). Our study aimed to compare catheter-related adverse events in breast cancer patients.</div></div><div><h3>Methods</h3><div>We conducted a <em>post hoc</em> analysis of a previously published multicentre RCT known as PICCPORT. Data pertaining to baseline characteristics, insertion specifics, complication rates, and patient satisfaction were collected for breast cancer patients who required long-term central venous catheters for cancer treatment. The primary endpoint was a composite variable encompassing thrombotic, occlusive, infectious, or mechanical complications, while patient satisfaction served as a secondary endpoint.</div></div><div><h3>Results</h3><div>Our analysis included 80 patients receiving PORT and 78 patients receiving PICC. There was no statistically significant difference in the incidence of complications between the PICC and PORT groups. Interestingly, PICC insertion was less painful than PORT insertion, although both groups reported low levels of pain.</div></div><div><h3>Conclusions</h3><div>While acknowledging the limitations of an underpowered <em>post hoc</em> subgroup analysis, our findings suggest that the well-established superiority of PORTs in terms of adverse events among cancer patients might not be as substantial for breast cancer patients in particular. Ultimately, the optimal strategy for selecting long-term access devices in breast cancer patients remains to be determined.</div></div><div><h3>Clinical trial registration</h3><div>NCT01971021.</div></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":"13 ","pages":"Article 100377"},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143151351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Barriers and enablers to recruiting participants within paediatric perioperative and anaesthetic settings: lessons learned from a trial of melatonin versus midazolam in the premedication of anxious children (the MAGIC trial)","authors":"Marie C. Hyslop ,&nbsp;Diana E. Papaioannou ,&nbsp;Robert Bolt ,&nbsp;Matthew J. Wilson ,&nbsp;Michael Bradburn ,&nbsp;Janet Clarkson ,&nbsp;Esther Herbert ,&nbsp;Nicholas Ireland ,&nbsp;Jennifer Kettle ,&nbsp;Amanda Loban ,&nbsp;Amy C. Norrington ,&nbsp;Christopher Vernazza ,&nbsp;Christopher Deery","doi":"10.1016/j.bjao.2024.100375","DOIUrl":"10.1016/j.bjao.2024.100375","url":null,"abstract":"<div><h3>Background</h3><div>Poor recruitment is one key reason for premature closure of randomised controlled trials. The Melatonin for Anxiety prior to General Anaesthesia In Children (MAGIC) trial was a multicentre randomised controlled trial of melatonin <em>vs</em> midazolam in the premedication of anxious children, before surgery. The trial ran between 2019 and 2022, closing early because of recruitment futility. This paper describes the challenges that arose during the trial and offers recommendations for the design of future perioperative trials.</div></div><div><h3>Methods</h3><div>A case-based approach was used to identify barriers to recruitment. As part of a qualitative sub-study, semi-structured interviews with local site teams, participants, and caregivers also explored barriers and enablers to recruitment.</div></div><div><h3>Results</h3><div>Issues encountered included time sensitivity within pressured environments; feasibility of paediatric assent; research pharmacy availability; variation in anaesthetist equipoise; multifactorial decision-making issues in premedication selection; and the Associate Principal Investigator scheme being unable to support trials within anaesthetic trainee rotations. Future paediatric perioperative medicine trials could consider funding for research pharmacy outside of working hours; conducting risk assessments for study drugs to be held on theatre admission units; and a tailored design of site feasibility assessments to help address variation in practice. Challenges remain for the feasibility of including anaesthetic trainees within the Associate Principal Investigator scheme structure.</div></div><div><h3>Conclusions</h3><div>There are significant challenges to recruitment for paediatric clinical trials in anaesthesia and perioperative medicine. The MAGIC trial highlighted variations within anaesthetic practice at individual, local, and regional levels. Lessons learned from the MAGIC trial identifies specific barriers to paediatric trial enrolment, offer solutions and discusses ongoing challenges.</div></div><div><h3>Clinical trial registration</h3><div>ISRCTN registry: ISRCTN18296119.</div></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":"13 ","pages":"Article 100375"},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143151353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The concerted actions of microRNA-29a and interferon-β modulate complete Freund's adjuvant-induced inflammatory pain by regulating the expression of type 1 interferon receptor, interferon-stimulated gene 15, and p-extracellular signal-regulated kinase","authors":"Chien-Cheng Liu ,&nbsp;Kuo-Chuan Hung ,&nbsp;Yu-Yu Li ,&nbsp;Eagle Yi-Kung Huang ,&nbsp;Chin-Chen Chu ,&nbsp;Lok-Hi Chow ,&nbsp;Ping-Heng Tan","doi":"10.1016/j.bjao.2024.100376","DOIUrl":"10.1016/j.bjao.2024.100376","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Previous research has shown that type 1 interferons (IFN), such as IFN-α and IFN-ß, possess antiviral and antinociception effects. Elevated levels of microRNA-29a (miR-29a) have been observed during inflammatory pain, and as miR-29a targets the type 1 IFN receptor (IFNR1), our study aimed to investigate the involvement of miR-29a, type 1 IFN, and IFNR1 in inflammatory pain.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Inflammatory pain was induced in male rats using complete Freund's adjuvant (CFA). The changes in miR-29a, IFN-ß, and IFNR1 were measured on Days 2, 3, 5, 7, and 10 post-CFA injection and expression of IFNR1, phospho-ERK (phosphorylated extracellular signal-regulated kinase) (p-ERK), extracellular signal-regulated kinase (ERK), and IFN-stimulated gene 15 (ISG15) were measured in rats that received an miR-29a inhibitor or miR-29a mimic.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Our results demonstrated elevated miR-29a expression (CFA 3 days: mean difference [95% confidence interval, CI]: 0.860 [0.657–1.062]; CFA 5 days: mean difference [95% CI]: 1.120 [0.917–1.322], &lt;em&gt;P&lt;/em&gt;&lt;0.001, &lt;em&gt;n&lt;/em&gt;=6) and decreased IFNR1 expression (CFA 3 days: mean difference [95% CI]: −0.300 [−0.470 to −0.130]; CFA 5 days: mean difference [95% CI]: −0.330 [−0.515 to −0.145], &lt;em&gt;P&lt;/em&gt;=0.004, &lt;em&gt;n&lt;/em&gt;=6) from Days 3–5 post-CFA induction, with IFN-ß expression showing a significant increase from Day 2 (F [3.30, 16.5]=34.3 for factor time, &lt;em&gt;P&lt;/em&gt;≤0.01, &lt;em&gt;n&lt;/em&gt;=6). Treatment with an miR-29a inhibitor alleviated CFA-induced mechanical allodynia and thermal hyperalgesia by Day 5 (&lt;em&gt;P&lt;/em&gt;&lt;0.001, &lt;em&gt;n&lt;/em&gt;=9), concomitant with upregulation of IFNR1 and ISG15 expression, and downregulation of p-ERK (IFNR1; CFA 5 days + miR-29a inhibitor &lt;em&gt;vs&lt;/em&gt; CFA 5 days; mean difference [95% CI]: 30.00 [20.31–39.69]; ISG15 conjugates; CFA 5 days + miR-29a inhibitor &lt;em&gt;vs&lt;/em&gt; CFA 5 days, mean difference [95% CI]: 1.000 [0.9144–1.086]; free ISG15, mean difference [95% CI]: 2.402 [2.171–2.633]; p-ERK; CFA 5 days + miR-29a inhibitor &lt;em&gt;vs&lt;/em&gt; CFA 5 days, mean difference [95% CI]: −32.00 [−34.10 to −29.90], &lt;em&gt;P&lt;/em&gt;&lt;0.001, &lt;em&gt;n&lt;/em&gt;=9). Furthermore, in naïve rats, administration of an miR-29a mimic-induced mechanical allodynia, which was reversed by an ERK antagonist (&lt;em&gt;P&lt;/em&gt;&lt;0.001, &lt;em&gt;n&lt;/em&gt;=6), associated with decreased IFNR1 and increased p-ERK expression (IFNR1; miR-29a mimic + dimethyl sulfoxide &lt;em&gt;vs&lt;/em&gt; naïve; mean difference [95% CI]: −57.00 [−65.78 to −48.22]; miR-29a mimic + ASN007 &lt;em&gt;vs&lt;/em&gt; naïve; mean difference [95% CI]: −60.00 [−71.00 to −49.00]. p-ERK; miR-29a mimic + dimethyl sulfoxide &lt;em&gt;vs&lt;/em&gt; naïve, mean difference [95% CI]: 52.00 [47.01–56.99]; miR-29a mimic + ASN007 &lt;em&gt;vs&lt;/em&gt; naïve, mean difference [95% CI]: 47.00 [42.51–51.49]; &lt;em&gt;P&lt;/em&gt;&lt;0.001, &lt;em&gt;n&lt;/em&gt;=6).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Inhibiting miR-29a expression attenuates inflammatory pain by modulating IFNR1, ISG15, and p","PeriodicalId":72418,"journal":{"name":"BJA open","volume":"13 ","pages":"Article 100376"},"PeriodicalIF":0.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143151352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a key performance indicator set for perioperative red blood cell transfusion","authors":"Akshay Shah ,&nbsp;Hayley G. Evans ,&nbsp;Antony J.R. Palmer ,&nbsp;Alan M. MacDonald ,&nbsp;Martha Belete ,&nbsp;Linda von Neree ,&nbsp;Michael M.F. Murphy ,&nbsp;Simon J. Stanworth ,&nbsp;Robbie Foy ,&nbsp;for the NIHR Blood and Transplant Research Unit in Data Driven Transfusion Practice","doi":"10.1016/j.bjao.2024.100372","DOIUrl":"10.1016/j.bjao.2024.100372","url":null,"abstract":"<div><h3>Background</h3><div>Perioperative red blood cell (RBC) transfusion is a common intervention in patients undergoing surgery but there is marked variation in practice. Key performance indicators (KPIs) are central to identifying deviation from agreed standards and improving clinical outcomes. We aimed to identify KPIs which can potentially be measured from routinely collected electronic healthcare records.</div></div><div><h3>Methods</h3><div>We undertook a three-stage process. First, we completed a scoping review to identify potential KPIs from relevant literature and clinical guidelines. Next, we conducted a modified RAND consensus process with a multidisciplinary panel including medical professionals, patients and public involvement members. The consensus panel rated these KPIs according to importance and feasibility.</div></div><div><h3>Results</h3><div>We identified 28 candidate KPIs covering the entire perioperative RBC transfusion process. The majority of the KPIs focused on improving patient care around the time of decision to transfuse RBCs and transfusion safety. Clinical outcome KPIs included hospital length of stay, hospital acquired infection, mortality, and hospital readmission at 30 and 90 days. Five candidate KPIs were judged as unimportant whilst there were concerns around the feasibility of measurement using routine data for 14 candidate KPIs. The panel identified nine potential KPIs for future testing.</div></div><div><h3>Conclusions</h3><div>Using a systematic, stepwise, transparent approach, we have identified a set of 28 KPIs for assessment, monitoring, and improvement of perioperative RBC transfusion. Future research is needed to further validate this set for external use and benchmarking between hospitals and departments.</div></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":"13 ","pages":"Article 100372"},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143151222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}