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Pegargiminase plus first-line chemotherapy in patients with nonepithelioid pleural mesothelioma: the ATOMIC-meso randomized clinical trial
No full textImportance: Arginine deprivation using ADI-PEG20 (pegargiminase) combined with chemotherapy is untested in a randomized study among patients with cancer. ATOMIC-Meso (ADI-PEG20 Targeting of Malignancies Induces Cytotoxicity-Mesothelioma) is a pivotal trial comparing standard first-line chemotherapy plus pegargiminase or placebo in patients with nonepithelioid pleural mesothelioma. Objective: To determine the effect of pegargiminase-based chemotherapy on survival in nonepithelioid pleural mesothelioma, an arginine-auxotrophic tumor. Design, setting, and participants: This was a phase 2-3, double-blind randomized clinical trial conducted at 43 centers in 5 countries that included patients with chemotherapy-naive nonepithelioid pleural mesothelioma from August 1, 2017, to August 15, 2021, with at least 12 months' follow-up. Final follow-up was on August 15, 2022. Data analysis was performed from March 2018 to June 2023. Intervention: Patients were randomly assigned (1:1) to receive weekly intramuscular pegargiminase (36.8 mg/m2) or placebo. All patients received intravenous pemetrexed (500 mg/m2) and platinum (75-mg/m2 cisplatin or carboplatin area under the curve 5) chemotherapy every 3 weeks up to 6 cycles. Pegargiminase or placebo was continued until progression, toxicity, or 24 months. Main outcomes and measures: The primary end point was overall survival, and secondary end points were progression-free survival and safety. Response rate by blinded independent central review was assessed in the phase 2 portion only. Results: Among 249 randomized patients (mean [SD] age, 69.5 [7.9] years; 43 female individuals [17.3%] and 206 male individuals [82.7%]), all were included in the analysis. The median overall survival was 9.3 months (95% CI, 7.9-11.8 months) with pegargiminase-chemotherapy as compared with 7.7 months (95% CI, 6.1-9.5 months) with placebo-chemotherapy (hazard ratio [HR] for death, 0.71; 95% CI, 0.55-0.93; P = .02). The median progression-free survival was 6.2 months (95% CI, 5.8-7.4 months) with pegargiminase-chemotherapy as compared with 5.6 months (95% CI, 4.1-5.9 months) with placebo-chemotherapy (HR, 0.65; 95% CI, 0.46-0.90; P = .02). Grade 3 to 4 adverse events with pegargiminase occurred in 36 patients (28.8%) and with placebo in 21 patients (16.9%); drug hypersensitivity and skin reactions occurred in the experimental arm in 3 patients (2.4%) and 2 patients (1.6%), respectively, and none in the placebo arm. Rates of poststudy treatments were comparable in both arms (57 patients [45.6%] with pegargiminase vs 58 patients [46.8%] with placebo). Conclusions and relevance: In this randomized clinical trial of arginine depletion with pegargiminase plus chemotherapy, survival was extended beyond standard chemotherapy with a favorable safety profile in patients with nonepithelioid pleural mesothelioma. Pegargiminase-based chemotherapy as a novel antimetabolite strategy for mesothelioma validates wider clinical testing in oncology.https://jamanetwork.com/journals/jamaoncology/fullarticle/281500
Clarifying the prevalence of OCD: A response to reader comments
Get PDF© 2024 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).This response to a reader's comment on our paper "The Global Assessment of OCD" addresses the critique regarding the stated prevalence of OCD as the fourth most common mental disorder. We acknowledge an oversight in our initial reference, discuss the variable prevalence rates from various studies, and highlight the significant disability caused by OCD. We have requested a correction to the original citation to reflect more recent findings, aiming to ensure accuracy in the discourse on OCD's public health impact.https://www.sciencedirect.com/science/article/pii/S0010440X24000439?via%3Dihu
Impact of Apolipoprotein E ε4 in alzheimer's disease: A meta-analysis of voxel-based morphometry studies
Get PDFcc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Com mercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly citedBACKGROUND AND PURPOSE: Alzheimer's disease (AD) is the most-prevalent form of dementia and imposes substantial burdens at the personal and societal levels. The apolipoprotein E (APOE) ε4 allele is a genetic factor known to increase AD risk and exacerbate brain atrophy and its symptoms. We aimed to provide a comprehensive review of the impacts of APOE ε4 on brain atrophy in AD as well as in mild cognitive impairment (MCI) as a transitional stage of AD. METHODS: We performed a coordinate-based meta-analysis of voxel-based morphometry studies to compare gray-matter atrophy patterns between carriers and noncarriers of APOE ε4. We obtained coordinate-based structural magnetic resonance imaging data from 1,135 individuals who met our inclusion criteria among 12 studies reported in PubMed and Google Scholar. RESULTS: We found that atrophy of the hippocampus and parahippocampus was significantly greater in APOE ε4 carriers than in noncarriers, especially among those with AD and MCI, while there was no significant atrophy in these regions in healthy controls who were also carriers. CONCLUSIONS: The present meta-analysis has highlighted the significant link between the APOE ε4 allele and hippocampal atrophy in both AD and MCI, which emphasizes the critical influence of the allele on neurodegeneration, especially in the hippocampus. These findings improve the understanding of AD pathology, potentially facilitating progress in early detection, targeted interventions, and personalized care strategies for individuals at risk of AD who carry the APOE ε4 allele.https://www.thejcn.com/DOIx.php?id=10.3988/jcn.2024.017
Development of a best practice guidance on online peer support for people with young-onset dementia
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Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).This work aimed to develop a Best Practice Guidance on online peer support for people with young-onset dementia (YOD). The Best Practice Guidance was developed through a systematic literature review, focus groups, an online survey, and interviews and consultations with people with YOD and professionals. The Best Practice Guidance consists of two parts. Part 1 contains information for people with YOD about what online peer support entails, what to expect from it, and how to get involved. Part 2 is aimed at those who facilitate or moderate online peer support (professionals or people with lived experience) and includes guidelines on how to optimize online peer support for people with YOD. The Best Practice Guidance on online peer support provides (1) people with YOD with evidence-based, relevant, and accessible information about what online peer support entails and how it could help them, (2) providers and facilitators with guidelines on how to optimize online peer support for people with YOD, and (3) healthcare professionals with a concise and accessible tool for signposting. Future research is needed to implement and disseminate the Best Practice Guidance among dementia organizations and healthcare practices and should include rigorous studies on the implementation and sustainability of online peer support for people with YOD.https://www.mdpi.com/2076-328X/14/9/74
NSAID-induced corneal melt as the first presentation of Sjögren’s syndrome
No full textA non-diabetic woman in her 80s presented 1 week following uncomplicated left eye cataract surgery complaining of decreased vision, gritty sensation and photophobia in the same eye. Postoperative treatment included G. Acular (Ketorolac Tromethamine 0.5%, NSAID: non-steroidal anti-inflammatory drug) and G. Tobradex (Tobramycin 0.3% and Dexamethasone 0.1%, antibiotic and steroid, respectively) each prescribed four times a day for 2 weeks. On examination, the patient had a corneal epithelial defect which progressed to a full-thickness perforation despite ceasing the NSAID drops. Cyanoacrylate glue application with a plastic drape patch failed to seal the perforation, and a full-thickness tectonic corneal transplant was performed. On investigation, the patient had positive anti-RO and anti-LA antibodies, suggesting a diagnosis of Sjögren’s syndrome. We advocate for careful preoperative assessment prior to cataract surgery, patient education, close follow-up and cautious medication use postoperatively including avoiding NSAID drops in patients with risk factors for postoperative dry eye disease.https://casereports.bmj.com/content/17/5/e25882
A Case Report of a Co-Amoxiclav-Induced Black Hairy Tongue
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Fahdawi et al. This is an open access
article distributed under the terms of the
Creative Commons Attribution License CCBY 4.0., which permits unrestricted use,
distribution, and reproduction in any
medium, provided the original author and
source are credited.A black hairy tongue is a benign, self-limiting condition characterized by the discolouration of the tongue due to defective desquamation. Clinical presentation varies, with most cases being asymptomatic although aesthetically unpleasant to the patient. Prevalence varies geographically, ranging from 0.6% to 11.3%. It can be triggered by various factors such as medications, smoking, alcohol, poor oral hygiene, or even underlying systemic conditions such as malignancy. Several antibiotics such as doxycycline, erythromycin, amoxicillin-clavulanate, metronidazole, and piperacillin-tazobactam, have been reported to cause black hairy tongues. Onset can range from a few weeks to as long as five weeks. Diagnosis relies on clinical assessment with a good history and visual examination. Definitive treatment remains unclear, but the condition typically improves by identifying and discontinuing the causative agent and maintaining adequate oral hygiene. Complications are rare, and the prognosis is excellent. This case report aims to raise awareness of the association between the black hairy tongue and co-amoxiclav, which may impose additional burdens on patients, healthcare providers, and the health system if failed to be recognized and treated appropriately.https://pubmed.ncbi.nlm.nih.gov/38770449
Utilizing both IgA tissue transglutaminase and IgG-deamidated gliadin peptide antibodies offers accurate celiac disease diagnosis without duodenal biopsy.
No full textBACKGROUND: Gastroenterologists still raise concerns about adopting a non-biopsy strategy for diagnosing celiac disease (CeD) in adults. AIM: To assess the performance of the concurrent detection of two autoantibodies targeting two independent antigens, tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP). METHODS: This prospective, multicenter, binational study collected consecutive patients with a high pre-test probability for CeD. Between 2018 and 2020, adults were enrolled at four Italian and one Argentinian center. Serology was also blindly analyzed by a central laboratory (Werfen, San Diego, USA) for tTG IgA and DGP IgG by Aptiva Particle-based multi-analyte technology (PMAT) assays. CeD diagnosis required histological confirmation of Marsh 3 damage. RESULTS: 181 adult patients with suspected CeD were enrolled (134 with histological diagnosis of CeD and 47 not histologically confirmed as CeD). Patients positive for both tTG IgA and DGP IgG (double positive) were predictive of CeD in 92.5 % of patients at >1x upper limit of normal (ULN). Double positivity for tTG IgA and DGP IgG, both at >10x ULN, had a 100 % positive predictive value for the presence of Marsh 3 histology. CONCLUSIONS: Incorporating DGP IgG alongside tTG IgA in a single-step approach can be considered a valid confirmatory strategy for definitive non-biopsy diagnosis of CeD.https://www.sciencedirect.com
Association Between Neutrophil-to-Lymphocyte Ratio and Sepsis Severity in ICU Patients.
Get PDFBackground Sepsis is a potentially fatal condition that necessitates prompt identification and assessment of its severity for effective management. However, evaluating sepsis severity using the Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores can be complex and costly. This study aimed to assess the association between neutrophil-to-lymphocyte ratio (NLR) and sepsis severity, as well as the role of NLR as a predictive indicator of sepsis severity in ICU patients. Methods This cross-sectional study was conducted among 180 ICU-admitted patients at Benazir Bhutto Hospital (BBH) in Rawalpindi, Pakistan, from January 2022 to January 2023. Participants were enrolled using defined inclusion and exclusion criteria along with consecutive sampling. Following ethical approval and informed consent, data were collected using a self-structured form. The study population was divided into three groups based on sepsis severity, which was assessed via the SOFA score. Data analysis was performed using IBM SPSS Statistics for Windows, Version 25.0 (Released 2017; IBM Corp., Armonk, NY, USA) through chi-squared tests, one-way ANOVA, Pearson's correlation, and a simple linear regression model, with a significance threshold set at p < 0.05. Results In the study population of 180 patients, the frequencies of sepsis, severe sepsis, and septic shock were 69 (38.34%), 86 (47.78%), and 25 (13.88%), respectively. Significant variations were observed among the three study groups in the means of the PaO2/FiO2 ratio, mean arterial pressure, Glasgow Coma Scale score, total bilirubin level, serum creatinine level, platelet count, SOFA score, neutrophil count, lymphocyte count, and NLR (p < 0.05). Pearson's correlation analysis indicated a strong positive correlation between the NLR and SOFA score, with a correlation coefficient (r) of 0.80 and significance at p < 0.001. Furthermore, linear regression analysis identified NLR as a significant predictor of sepsis severity, with a beta coefficient (β) of 3.55 and a 95% CI of 1.92-5.60 (p < 0.001). Conclusions In the current study, a positive and significant correlation was found between the NLR and the severity of sepsis. Higher NLR values were associated with increased SOFA scores, indicating a greater severity of sepsis. This study supports the use of NLR as a complementary and cost-effective tool for the early detection of high-risk patients with sepsis, facilitating timely interventions and improving outcomes, particularly in under-resourced healthcare settings
Feasibility of embedding orthopaedic clinical trials into national registries: a pilot quality improvement study for the UK Non-Arthroplasty Hip Registry (UK-NAHR).
No full textThe integration of 'Registry-based Randomised Control Trials' (RRCT) into national registries has the potential to catalyse prospective research, enhancing the evidence base for practice. The aim of this study was to assess the feasibility of embedding a trial within the UK Non-Arthroplasty Hip Registry. This was a national observational, multi-centre study. Six pilot sites within the UK were provided with additional support for data collection. We compared the ability of these pilot sites to collect data with the ability of centres where no additional support was provided. We collected information on patient compliance, efficacy and adverse events of drugs routinely used after hip preserving surgery. The primary outcome measure was compliance with data collection in these centres at 30 and 90 days after surgery. Our intention was to assess the feasibility of, and factors influencing, the capturing data for interventional registry trials in the future. Two hundred and twenty-eight patients were enrolled in the Non-Arthroplasty Hip Registry during the study period (114 within pilot centres and 114 in non-pilot centres). Pilot centres had a mean follow-up compliance of 79% (30 days) and 69.4% (90 days) in contrast to 55% (30 days) and 47% (90 days) in the non-pilot centres (P = 0.009/P = 0.0058). The study revealed that supplementary administrative support resulted in improved compliance. However, deficient administration systems negatively impacted follow-up, and surgeon motivation emerged as a crucial determinant in ensuring robust follow-up. The lessons learned from this feasibility trial could be useful for any national registry embedding prospective, registry-based trials
The recognition and therapeutic management of self-harm and suicide prevention
No full textNo abstract availablehttps://global.oup.com/academic/product/mental-health-nursing-skills-9780192864048?cc=us&lang=en