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A Comparison of the Molecular Pharmacological Properties of Current Short, Long, and Ultra‐Long‐Acting β2‐Agonists Used for Asthma and COPD
Full text linkβ-agonists have been used in asthma for 120 years. There are two recent changes: ultra-long-acting agonists for COPD and new asthma guidelines recommending formoterol/ICS inhalers phasing out short-acting salbutamol inhalers. Few studies directly compare the molecular pharmacological properties of short (salbutamol, terbutaline, fenoterol), long (formoterol, salmeterol), and ultra-long-acting (indacaterol, olodaterol, vilanterol) β2-agonists. Here, the in vitro molecular pharmacological properties of affinity, selectivity, intrinsic efficacy, and duration of β2-agonists at human β2 and β1-adrenoceptors and the 4 β2-polymorphisms stably expressed in CHO cells were directly compared using radioligand binding and functional studies. Whilst short-acting drugs were similar, there was huge variation and complete overlap in the molecular pharmacological properties of drugs labeled as long and ultra-long-acting β2-agonists. Salmeterol and vilanterol were highly β2-selective (> 1000-fold) whereas indacaterol was similar to salbutamol (40-fold). Formoterol and indacaterol were the most efficacious, whereas salmeterol had the longest duration of binding. Salmeterol and vilanterol utilize a β2-specific exosite (β2-H296-K305) for high affinity and selectivity (that does not affect intrinsic efficacy or duration) whilst the β2-selectivity of formoterol and olodaterol resides elsewhere. Duration of binding closely correlated with lipophilicity. β2-polymorphisms had no substantial effect on β2-agonist properties. Comparison with other β-ligands suggests that affinity and duration could both be improved further. However, given the very wide range of molecular pharmacological properties of β-agonists that are clinically effective and widely used, non-pharmacological properties (physiochemical, patient factors, devices and combination inhaler availability) may be as important in final clinical patient outcomes as the molecular pharmacological properties of the individual β2-agonists themselves.https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/prp2.7015
Levetiracetam in epilepsy and autism spectrum disorder : analysis of safety, tolerability, and efficacy
No full text© 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).PURPOSE: One in five people with autism spectrum disorder have epilepsy and take Anti-Seizure Medications (ASM). However, the impact of ASM on people with autism is under researched. This study evaluates the efficacy and tolerability of Levetiracetam (LEV) for autistic people and epilepsy. METHOD: Data was derived from the English Epilepsy Research Database Register which compares ASM responses in those with neurodevelopmental disorders to those without. Age range was 18-50 years as there were no autistic research participants with autism prescribed LEV over 50. Twelve-month ASM data, including withdrawal rate, seizure frequency and adverse effects were compared. Fisher's exact test was used to assess univariate associations between outcomes and autism with significance accepted as p < 0.05. Logistic regression was used to assess autism group differences after adjustment for potential confounders (age, gender, presence of baseline physical and mental health conditions). RESULTS: Of 175 (aged 18-50) research participants across 18 NHS Trusts, prescribed LEV between 2000 and 2020, 40 were autistic. There was no significant association between withdrawal rate (P = 0.626), or grouped side effects (physical P = 0.165, mental health P = 0.791). Autism was significantly associated with aggression with LEV in univariable analysis but this association was no longer significant after accounting for multiple testing A significant non-linear relationship between efficacy and the autism group (P < 0.001) was found. CONCLUSIONS: This study supports the use of LEV for people with autism and epilepsy as there is no difference in response noted to those without autism. However, they may have less prominent changes in efficacy.https://www.epilepsybehavior.com/article/S1525-5050(25)00418-4/fulltex
Friday night acute kidney injury: chest infection masking Antineutrophil Cytoplasmic Antibody Vasculitis
No full textAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) includes a group of autoimmune disorders resulting in the production of autoantibodies to neutrophil proteins (leukocyte proteins, proteinase 3 (PR3)-ANCA or myeloperoxidase proteins (MPO)-ANCA). There are three subtypes of AAV based on ANCA serotypes: PR3+ AAV, MPO+ AAV, and ANCA+. These rare disorders present with a wide spectrum of symptoms with involvement of multiple organs, including the heart, kidneys, eyes, ears, brain, spinal cord, nerves, and musculoskeletal system, making them difficult to diagnose promptly. This impacts the prognosis of AAV, as involvement of major organs can increase recurrence rates and lead to a poor prognosis, while timely diagnosis can lead to full recovery. Treatment options mainly involve immunosuppression with steroids, rituximab, methotrexate, and cyclophosphamide to maintain remission. We discuss a case of granulomatosis with polyangiitis in an adult male. We believe this report will help highlight timely diagnosis and interventions, overall improving the prognosis of patients.https://www.cureus.com/articles/349053-friday-night-acute-kidney-injury-chest-infection-masking-antineutrophil-cytoplasmic-antibody-vasculitis#!
Clinical audit : supporting post detox abstinence : discussion of relapse prevention medications by community addiction services prior to referral for inpatient detoxification
No full textAims: Without a plan to support ongoing abstinence, detoxification ("detox") could increase, rather than reduce, risks to a patient. Before referring for inpatient detox from alcohol or opioids, community teams are expected to discuss relapse prevention medications (RPMs) with patients, as part of their wider support plan. This clinical audit examined whether RPMs were mentioned in referrals by community teams to our inpatient detox unit. Method(s): We examined referrals for patients admitted to The Level Nottingham inpatient detox unit between 1 January and 31 August 2024. Of a total of 215 patients that completed opioid or alcohol detox, a random sample of 50 were selected, stratified according to referring team. Referral forms and running notes were used to assess compliance with the following criteria: 1. Referring teams mention RPMs (whether to be considered or not considered). 2. Referring teams provide blood test investigations. There was no previous literature or audit to specify a standard, so, given the importance of the issues under consideration, this was set as 100% for each criterion. We also extracted: whether patients were planned to go to residential rehabilitation after detox, and, where relevant, which RPMs were mentioned and time from blood test results to referral and to admission. Result(s): 68% of referrals were for alcohol, and 24% for opioid, detoxification (2% were for alcohol and opioid, and 6% for other substances). 40% of referrals for alcohol, and 77% of referrals for opioid, detoxification did not mention RPMs. 29% of referrals for alcohol, and 31% of referrals for opioid, detoxification did not mention RPMs and were not planned to go to residential rehabilitation (considered as some of these settings do not accept patients on RPMs, focusing solely on psychosocial support). 48% of referrals for any detoxification did not have blood test results available. Where blood test results were available, median time from test results was 22 days to referral and 85 days to admission. Conclusion(s): During the study period, an estimated one-third of referrals for alcohol or opioid detoxification did not mention RPMs (and were not going to residential rehabilitation post inpatient stay). Approximately half of admissions did not have blood test results available. The above is likely to delay the prescription of RPMs, and potentially increase the risk of relapse post-detoxification. Recommendations to increase performance include discussions with referrers, changes to the referral form, and changes to referral screening.https://www.cambridge.org/core/journals/bjpsych-open/article/clinical-audit-supporting-post-detox-abstinence-discussion-of-relapse-prevention-medications-by-community-addiction-services-prior-to-referral-for-inpatient-detoxification/D6CD6B978978D19058F166A9884DEAF
Evaluating PRN medication prescribing practices in mental health services : a comparative audit following a serious incident
No full textAims: PRN (pro re nata) medications are widely used in mental health settings but are prone to misuse and prescribing errors. A serious incident involving a patient's death linked to excessive PRN medication supply prompted an initial audit to evaluate compliance with prescribing standards. A re-audit was conducted to assess progress and identify ongoing challenges. Method(s): Two prospective audits were conducted across an inpatient acute ward and a rehabilitation centre. The initial audit (29/07/2024-06/08/2024) and re-audit (29/01/2025-06/02/2025) reviewed medication cards, Rio (electronic patient notes) and EPMA (Electronic Prescribing and Medicines Administration) for 31 patients prescribed PRN medications. Compliance was assessed against 13 predefined standards, including generic naming, dose intervals, BNF compliance, and regular reviews. Result(s): Sustained Full Compliance: Both audits demonstrated 100% compliance in key areas: generic naming, specified administration routes, separate prescriptions for multiple routes, adherence to BNF limits, clear indications for use, and rewriting altered prescriptions. Key Improvements: Minimum dose interval specification improved from 64.5% to 93.5%. Maximum dose documentation increased from 96.7% to 100%. Regular ward round reviews rose dramatically from 3.2% to 64.5%. Discontinuation of unused PRN medications (>1 month) improved from 0% to 22.2%. Review of PRN medications used regularly (>72 hours) increased from 0% to 28.5%. Documentation of regular vs. PRN use improved from 33.3% to 44.4%. Ongoing challenges: Review of PRN medications used regularly (>72 hours) remained low at 28.5%. Discontinuation of unused PRN medications (>1 month) was only 22.2%. Documentation of regular vs. PRN use remained below 50%. Conclusion(s): The re-audit demonstrates significant progress in dose interval specification, maximum dose documentation, and ward round reviews. However, challenges persist in the regular review and discontinuation of PRN medications, as well as in documenting regular vs. PRN use. Continued focus on these areas is essential to ensure patient safety and adherence to best prescribing practices. Recommendations: Key recommendations include integrating PRN standards into doctor inductions, involving pharmacists in ward rounds, and conducting regular re-audits to monitor progress and sustain improvements. Disseminating guidelines and providing feedback to medical teams are essential steps toward achieving full compliance and enhancing patient safety.https://www.cambridge.org/core/journals/bjpsych-open/article/evaluating-prn-medication-prescribing-practices-in-mental-health-services-a-comparative-audit-following-a-serious-incident/8AFCED2BA07A1EB9A24DC5D9750C85D
Improving surgical outcomes through non-technical skills: the case for better training and national evaluation
Full text linkEffective communication and teamwork are as crucial as technical proficiency for achieving positive surgical outcomes. Non-technical skills (NTS)-including communication, leadership, decision-making, and situational awareness— enhance surgical performance by fostering awareness and capability among both trainees and experienced surgeons. Despite growing recognition of its importance, NTS training is not uniformly implemented in surgical education, leaving a significant gap. This study examines opportunities to expand NTS training within surgical practice. A survey at a local hospital assessed the availability of NTS training and perceived needs among 38 surgical trainees and professionals. The majority acknowledged the value of NTS in improving clinical performance but reported limited focus on human factors in daily practice. Complementing the survey, a literature review was conducted across Medline, EMBASE, and PsycINFO databases, identifying 414 relevant articles, 114 of which focused on clinical or educational contexts. Of these, 61 studies emphasized psychomotor skill assessment via direct observation, patient outcomes, and peer feedback, underscoring the critical role of effective evaluation methods. Findings indicate that while NTS training is appreciated, its effectiveness depends heavily on feedback quality and team dynamics, particularly in addressing challenging behaviors. The study highlights the need for enhanced training design and robust feedback mechanisms. Although current evidence linking NTS training to improved patient outcomes is largely anecdotal, there is strong professional support for broader implementation. The authors advocate for a systematic, nationwide evaluation to determine the true impact of NTS training on surgical performance and outcome
Novel finding of pulmonary embolism following tirzepatide (Manjaro) use in a young adult without risk factors of venous thromboembolic events
No full textA woman in her early 40s presented with pleuritic chest pain and shortness of breath, which had progressively worsened over 20 days following initiation of tirzepatide (Manjaro). Her D-dimer level was elevated at 1340 ng/mL, prompting a CT pulmonary angiogram that confirmed right main pulmonary artery pulmonary embolism (PE). The patient had no identifiable provoked or unprovoked risk factors for venous thromboembolisms (VTEs). To our knowledge, this is the first reported case of PE that might be associated with the use of tirzepatide worldwide. The relationship between tirzepatide and VTEs events remains unclear. This case highlights the need for further research to explore the incidence and underlying mechanisms of VTEs in patients receiving tirzepatide.https://casereports.bmj.com/content/18/7/e26656
Robot-assisted radical nephroureterectomy for locally advanced upper tract urothelial carcinoma: a multicenter study by the Junior ERUS/YAU Working Group on Robot-assisted Surgery
No full textIntroduction Aim of the study was investigate outcomes of patients affected by locally advanced (pT3-pT4 and/or pN+) upper tract urothelial carcinoma (UTUC) and treated with robot-assisted radical nephroureterectomy (RNU). Materials and methods Clinical and surgical data of newly-diagnosed UTUC patients referring to 9 high-volume centres from January 2019 to March 2023 undergoing RNU were collected. Results 191 patients showed locally advanced disease. Da Vinci and Hugo RAS ™ System were employed in 95.8 % and 4.2 % of cases, respectively. Bladder cuff removal was carried out in 161 (84.3 %) patients, by using either an intravesical and extravesical approach in 50 (31.1 %) and 111 (68.9 %) respectively. Open and robotic approaches for bladder cuff removal were preferred in 107 (66.5 %) and 54 (33.5 %) patients, respectively. Lymph node dissection was performed in 55 % of patients. Median follow up was 19 (IQR 10–23) months and 31 (16.4 %) patients experienced bladder recurrence. On multivariate analysis, in those patients receiving RNU and bladder cuff removal, the approach for bladder cuff management (extravesical vs intravesical) was the only independent predictor of bladder recurrence (hazard ratio [HR]: 1.34; 95 % confidence interval [CI] 1.12–2.11; p = 0.03). Surgical approach for bladder cuff management (open vs robot) was not independently associated with bladder recurrence or tumor progression (both p > 0.05) Conclusions In experienced hands, the robotic approach showed satisfactory survival outcomes also for the surgical treatment of pathological locally advanced UTUC. Extravesical approach for bladder cuff management may be burdened by a higher risk for bladder recurrence in locally advanced disease.https://www.ejso.com/article/S0748-7983(25)00824-8/abstrac
The impact of extra-oral facial prosthesis on quality of life for people with aquired defects : a systematic review
No full textPurpose: Acquired facial defects caused by traumatic injury or malignancy are likely to affect one’s physical wellbeing. They may lead to segregation from society due to the stigma and the subjective opinions of the individual, decreasing their overall quality-of-life (QoL). Facial prostheses are suitable forms of rehabilitation for people with acquired facial defects. Recently, QoL has been receiving attention important in evaluating patient outcomes. The aim of this systematic review was to synthesise research reporting the impact of extra-oral facial prostheses on QoL for individuals with an acquired facial defect. Materials and methods: A systematic review was undertaken following Joanna Briggs Institute and PRISMA guidelines. The protocol was registered (CRD42024403538), and the searches were performed in six databases from inception to 5th August 2024. Results: 1291 records were retrieved after review ten articles were retained for inclusion. The papers were grouped into those assess people with acquired facial defects in either the auricular, nasal, or orbital regions. A total of 363 people were represented. Six QoL measures were used. Across all three groups, QoL improved post-prosthesis. Although nasal prosthesis users reported lower physical and social functioning than those with auricular prostheses. Conclusions: All ten studies reported positive impact on QoL of prosthesis, however their generalizability is limited by varying methodologies and QoL measures, none of which are designed for use with prosthesis users. Despite these limitations, QoL improvements were seen regardless of follow-up duration or prior prosthetic experience. Future research should use standardized, prosthesisspecific QoL measures for clearer comparisons.https://ij-mp.com/index.php/ijmp/article/view/5
Quality improvement project to enhance adherence to RCEM standards for patients with paracetamol overdose.
Full text linkBACKGROUND: Delayed or inconsistent administration of N-acetylcysteine (NAC) for paracetamol overdose in the emergency department (ED) poses a risk to patient safety, with current Royal College of Emergency Medicine (RCEM) standards often not being met. The traditional 21-hour NAC regimen is associated with adverse drug reactions, medication errors and prolonged admissions. The Scottish and Newcastle Acetylcysteine Protocol (SNAP) was introduced as a simpler alternative with comparable efficacy. This quality improvement project (QIP) aimed to improve compliance with RCEM standards by implementing targeted interventions while also reducing the length of inpatient stay and maintaining patient safety. METHOD: This QIP was conducted at Royal Derby Hospital using a multidisciplinary, systematic approach based on Plan-Do-Study-Act cycles. Baseline data were collected from 100 randomly selected patients (November 2021-May 2022) and compared with outcomes during a 52-week intervention period (September 2023-August 2024). Interventions included educational sessions, quick reference materials and enhanced prescribing tools. Data were analysed for compliance with RCEM standards, adverse events (liver function derangement and anaphylactoid reactions) and system-level measures, such as length of inpatient stay and timing of paracetamol plasma levels. RESULTS: A total of 214 patients were included. Compliance with RCEM standard 1 improved from 36% to 43%. No change was noted for standards 2 and 3. Median inpatient stay decreased from 35 hours to 30.5 hours. No significant differences were found in adverse events. Special cause variation was identified in paracetamol plasma level timing, attributed to early sampling in some cases. CONCLUSION: This QIP addressed problems of delayed or inconsistent NAC administration in the ED by improving compliance with RCEM standard 1 and reducing inpatient stay while maintaining patient safety. Although standards 2 and 3 did not improve, the interventions proved cost-effective, feasible and scalable. Future work should focus on sustaining improvements and exploring patient-centred outcomes across diverse healthcare settings