bluuebunny/crossref_metadata_2025_split huggingface dataset:
The barriers to and facilitators of implementing early mobilisation for patients with delirium on intensive care units: A systematic review
Authors: Bennion Jacqueline , Manning Christopher , Mansell Stephanie K , Garrett Roger , Martin Daniel 
Published: March 2024

Background: Early mobilisation of critically ill patients remains variable across practice. This study set out to determine barriers to and facilitators of early mobilisation for patients diagnosed with delirium in the intensive care unit (ICU). Methods: A mixed-methods descriptive systematic review. Electronic databases (AMED, BNI, CINAHL Plus, Cochrane Library, Medline and EMBASE) were searched for publications up to 22nd December 2021. Independent reviewers screened studies and extracted data using Covidence Systematic Review Management software. Data were summarised according to frequency (n/%) of barriers and facilitators. Thematic analysis of qualitative studies was carried out in order to address the secondary aim. Quantitative studies were assessed using the GRADE quality assessment tool. Qualitative studies were analysed according to the GRADE-CERQual quality assessment tool. This study was prospectively registered on PROSPERO (CRD 42021227655). Results: Ten studies met the inclusion criteria. Quantitative findings demonstrated the presence of delirium was the most common reported barrier to early mobilisation. The most common facilitator was ICU staff experience of positive outcomes as a result of early mobilisation interventions. Thematic analysis identified six main themes that may describe potential meanings behind these findings: (1) knowledge, (2) personal preferences, (3) perceived burden of delirium, (4) perceived complexity, (5) decision-making and (6) culture. Conclusion: These findings highlight the reported need to further understand the impact and value of early mobilisation as a non-pharmacological intervention for patients diagnosed with delirium in ICU. Evaluation of early mobilisation interventions involving key stakeholders may address these concerns and provide effective implementation strategies.
Acceptability of and satisfaction with continuous glucose monitoring in pregnant women with type 2 diabetes mellitus: A service improvement project
Authors: Beriwal Sridevi , Re Federica , Gibson Sharon , Thanabalasingham Gaya , Owen Katharine R. , Houlden Ruth , Malakasis Anastasios , Hirst Jane E 
Published: March 2024

Background There are limited data regarding intermittently scanned continuous glucose monitoring (isCGM) in pregnancy for women with Type 2 diabetes. We have tested the acceptability and feasibility of an isCGM method using Libre device. Method In a hospital-based service improvement project, 23 pregnant women (March 2022-April 2023), with Type 2 diabetes got isCGM for monitoring from 20 weeks until delivery. Women completed a structured and validated questionnaire assessing satisfaction, equipment issue, relationship with diabetes team. Results Two-thirds of the women were satisfied with the convenience and found it reliable. 86% wanted to use it for future pregnancies, and 90% would recommend it to others. Sensor falls off was seen in three obese women and about a tenth felt the reliability was poor in extreme ranges of sugar levels. The relationship with the diabetes team was rated high. Conclusion isCGM could be a useful and well-received tool for improving glycaemic control in pregnancies with Type 2 diabetes.
Patient Perception of Social Media Use by Orthopaedic Surgeons: A Pilot Study
Authors: Johnson Alexander J. , Wharton Benjamin R. , Geraghty Elisabeth H. , Bradsell Hannah , Ishikawa Andrew , McCarty Eric C. , Bravman Jonathan T. , Frank Rachel M. 
Published: March 2024

Background: Social media (SM) use by orthopaedic surgeons is becoming increasingly common; nonetheless, it needs to be clarified how patients perceive the content posted by physicians. Purpose: To characterize SM content posted by orthopaedic surgeons while investigating patient perceptions of this content and how it may influence their health care decisions. Study Design: Cross-sectional study. Methods: Posts on SM outlets by orthopaedic surgeons were reviewed and categorized. A survey to assess patient perception of these categories was administered between December 2021 and February 2022 in the clinics of 3 orthopaedic surgeons. Survey results were analyzed for differences in patient SM use and perception of SM content types. Results: There were 250 completed surveys. SM use was high among all age groups; however, the 18 to 24 years (87.1%) and 25 to 34 years (86.4%) age groups were more likely than older age groups to report daily use ( P = .002). Overall, 17% of patients reported using SM to see information about their health care at least once per month, 21% reported reviewing the SM account of a physician at least once per month, 19% reported that they were likely or very likely to view the SM account of their physician, and 23% reported that SM content was likely or very likely to influence which physician they see. Patients held the most consistently positive view of posts that educated patients, discussed sports team coverage, and provided patient testimonials. Patients had consistently neutral views of posts educating colleagues, discussing presentations at national meetings, displaying aspects of surgeons’ personal lives, and supporting marginalized groups. Several post categories elicited highly polarized responses—including those discussing research publications and showing surgical techniques or pictures/videos taken during surgery. Respondents had a consistently negative response to posts making political statements. Conclusion: SM is likely a useful tool to help physicians interact with patients. Physicians who wish to interact with patients should consider posting content viewed most positively—including posts educating patients, discussing sports team coverage, and providing patient testimonials. Content that is viewed less favorably should be posted sparingly or with a sensitive tag.
Extended regular use of kinetic oscillation stimulation (KOS) in refractory chronic migraine: case report of a first, single-subject experience
Authors: Liaci Giorgio , Altamura Claudia , Brunelli Nicoletta , Fofi Luisa , Prudenzano Maria Pia , Vernieri Fabrizio 
Published: March 2024

Background: Kinetic Oscillation Stimulation (KOS) is a novel and non-invasive neuromodulation method for migraine therapy. Emerging evidence suggests that applying low-frequency intranasal vibrations to the sphenopalatine ganglion (SPG) could be a safe and effective option for migraine treatment. Case report: We present a case of a 60-year-old man affected by refractory chronic migraine with a history of failure or progressive ineffectiveness of multiple approved therapies. Given the limited available options, we proposed the patient a 6-week treatment cycle with KOS. After 1 month, monthly migraine days (MMD) dropped from 18 to 7, with significant pain reduction by week 6. However, the benefits were not sustained after discontinuation, requiring a second stimulation cycle after 3 months, which yielded an even faster and more significant response. Conclusions: This experience reveals KOS safety and effectiveness for long-term SPG neuromodulation, highlighting the potential of focusing treatment on the trigeminal-autonomic reflex (TAR) as a promising direction to pursue.
Rimegepant as an acute treatment in a refractory migraine patient non-responder to two anti-CGRP monoclonal antibodies and triptans: Case report and pharmacological considerations
Authors: Burgalassi Andrea , Vigani Giulia , Boccalini Alberto , De Cesaris Francesco , Mannaioni Guido , Chiarugi Alberto , Geppetti Pierangelo , Iannone Luigi Francesco 
Published: March 2024

Background: Small molecule receptor antagonists (gepants), or monoclonal antibodies (mAbs) against calcitonin gene-related peptide (CGRP) have recently become available for migraine prophylaxis and/or acute treatment. Considering their shared mechanisms of action, if the failure to an anti-CGRP(R) mAbs preclude the effectiveness of gepants or vice versa is still unknown. Herein, we report the first case of a patient with refractory migraine responsive to the acute use of rimegepant that previously failed two different anti-CGRP(R) mAbs and with no response to other acute treatments. Finally, we performed a literature review on the use of gepants in patients that failed other anti-CGRP and/or triptans. Case: A 56-year-old female with a long history of chronic migraine without aura, fulfilling the EHF definition for a diagnosis of refractory migraine. Overall, the patient treated five not-consecutive migraine attacks. All of them were treated according to the predefined criteria. The mean (±SD) NRS before rimegepant assumption was 7.8 ± 0.9, all attacks cause at least severe impairment at onset, and no rescue medications were used. Pain free at 2 hours was achieved in three out of five attacks (60.0%), with no recurrence of migraine in the following 24 hours. The patient reported also a sustained benefit the day after the drug assumption. The response pain free was achieved after a mean time of 13.3 ± 4.5 minutes considering only attacks successfully treated (three out of five attacks). No adverse events were reported. Conclusions: In conclusion, rimegepant for acute treatment may be a viable option in patients with partial or no response to triptans that failed preventive treatments targeting the CGRP pathway, regardless to ligand or receptor. The failure of anti-CGRP(R) mAbs does not necessarily preclude the use of gepants (acute and/or preventive), but further studies are urgently needed to provide evidence on the efficacy of these treatments in managing drug-resistant migraine and to identify novel treatments for patients.
Treatment Outcomes of Patients With Overlapping Eosinophilic Esophagitis and Gastroesophageal Reflux Disease After Antireflux Surgery
Authors: Lee Christopher J. , Farrell Timothy M. , Dellon Evan S. 
Published: March 2024

Background: The relationship between eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) is complex, and there are scant data about the role of fundoplication when GERD/EoE overlap. We aimed to describe treatment outcomes of patients with GERD/EoE overlap undergoing antireflux surgery. Methods: We conducted a retrospective cohort study of patients with overlapping EoE and GERD who had undergone laparoscopic fundoplications. Patient demographics, clinical characteristics, EoE history, and procedural/surgical data were extracted from the medical record. Endoscopic and histologic responses were assessed for pre- and post-operative endoscopies. Results: We identified 10 patients with GERD/EoE overlap who underwent antireflux surgery, and 9 patients underwent post-operative repeat EGD. All patients had heartburn and regurgitation symptoms that were refractory to PPI and/or persistent erosive disease, and also demonstrated signs/symptoms of EoE such as dysphagia (80%), food impaction (60%), fibrostenotic disease requiring dilation (70%), and lack of symptom or histologic response to topical steroids (70%). Patients demonstrated expected improvements in erosive esophagitis and hiatal hernia. The peak eosinophil count improved from 47.1 ± 35.9 eos/hpf to 7.8 ± 12.3 eos/hpf ( P = .02). Total EREFS score decreased from 3.0 ± 2.2 to 1.2 ± 2.3 ( P = .009). Conclusions: Patients who have GERD/EoE overlap can have endoscopic and histologic improvement in both conditions after fundoplication. This implies that in a subset of patients, GERD may drive an EoE response, and this must be recognized for successful treatment.
EsophaCap Sponge Cytology Screening for Esophageal Squamous Cell Dysplasia and Carcinoma is Feasible in a High-Risk Area in Western India
Authors: Bhatt Maunil , Sridhar Praveen , Asokan Sainath , Shah Parth , Gandhi Fenil , Shah Pratiksha , Patel Parth , Suzuki Kei , Rajput Sanjay , Parmar Vipal , Mehta Bhavna , Godfrey Tony E. , Litle Virginia R. 
Published: March 2024

Objective: Conventional endoscopy remains the gold standard for detecting esophageal squamous cell carcinoma (ESCC) despite its high cost and need for expertise. In resource-poor regions, a less labor-intensive yet accurate screening tool is needed. The purpose of this study is to assess feasibility of establishing a non-endoscopic screening program in rural India and to test the diagnostic accuracy of the EsophaCap swallowable sponge in detecting ESCC in a high-risk patient population. Methods: A prospective cohort study was conducted between 2017 and 2019, in which subjects with risk factors for ESCC (tobacco smoking or chewing, betel nut/leaf, alcohol and hot beverage consumption) were approached during upper endoscopy visits at a clinic in Western India. After obtaining EsophaCap sponge cytology samples, random endoscopic biopsies were obtained at 20 and 30 cm from the incisors. Histologic diagnoses were confirmed and select biopsy samples were sequenced for genomic aberrations. Visual Analog Scale (VAS) scores were used to assess patient experience of sponge swallowing (range 1-5, “very comfortable” to “very uncomfortable”). Results: In our cohort of 178 patients, 157 (88%) were males. Mean age was 52 ± 12 years. Sixty-eight (38%) patients were current cigarette or bidi smokers; 132 (74%) patients were daily tobacco chewers, and 83 (47%) patients chewed betel nuts/leaves on a daily basis. Forty-six (26%) patients were daily alcohol users and 151 (85%) patients drank ≥3 hot beverages per day. The median number of risk factors per patient was 3. The first-time swallow rate of the encapsulated sponge was successful in 190/200 (95%) patients. Median VAS score was 2 (“comfortable”). EsophaCap cytology revealed 6 (3%) patients with atypical squamous cells of unknown significance (ASCUS) and 3 (1%) patients with dysplasia. Based on the endoscopic biopsies, 6 (3%) patients had ESCC, 4 (2%) patients had lesions with squamous dysplasia, and 63 (35%) patients had esophageal leukoplakia. Four patients classified as ASCUS pathology via EsophaCap were normal, benign, or leukoplakia via endoscopy. EsophaCap’s sensitivity and specificity for detecting dysplasia or ESCC by histology was 30% and 97%, respectively. Conclusions: Establishing a non-endoscopic screening program in a high-risk area with language barriers and low medical literacy is very safe and feasible. EsophaCap may help identify ASCUS patients in need of serial endoscopic monitoring. Further studies of combined sponge cytology with immunohistochemistry studies are necessary to improve accuracy of ESCC screening.
Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial
Authors: Kenet Gili , Nolan Beatrice , Zulfikar Bulent , Antmen Bulent , Kampmann Peter , Matsushita Tadashi , You Chur-Woo , Vilchevska Kateryna , Bagot Catherine N. , Sharif Azizan , Peyvandi Flora , Young Guy , Negrier Claude , Chi Jiarui , Kittner Barbara , Sussebach Christian , Shammas Fadi , Mei Baisong , Andersson Shauna , Kavakli Kaan 
Published: March 2024

Abstract
Fitusiran, a subcutaneous investigational small interfering RNA therapeutic, targets antithrombin to rebalance hemostasis in people with hemophilia A or B (PwHA/B), irrespective of inhibitor status. This phase 3, open-label study evaluated the efficacy and safety of fitusiran prophylaxis in males aged ≥12 years with hemophilia A or B, with or without inhibitors, who received prior bypassing agent (BPA)/clotting factor concentrate (CFC) prophylaxis. Participants continued their prior BPA/CFC prophylaxis for 6 months before switching to once-monthly 80 mg fitusiran prophylaxis for 7 months (onset and efficacy periods). Primary end point was annualized bleeding rate (ABR) in the BPA/CFC prophylaxis and fitusiran efficacy period. Secondary end points included spontaneous ABR (AsBR) and joint ABR (AjBR). Safety and tolerability were assessed. Of 80 enrolled participants, 65 (inhibitor, n = 19; noninhibitor, n = 46) were eligible for ABR analyses. Observed median ABRs were 6.5 (interquartile range [IQR], 2.2-19.6)/4.4 (IQR, 2.2-8.7) with BPA/CFC prophylaxis vs 0.0 (IQR, 0.0-0.0)/0.0 (IQR, 0.0-2.7) in the corresponding fitusiran efficacy period. Estimated mean ABRs were substantially reduced with fitusiran by 79.7% (P = .0021) and 46.4% (P = .0598) vs BPA/CFC prophylaxis, respectively. Forty-one participants (63.1%) experienced 0 treated bleeds with fitusiran vs 11 (16.9%) with BPAs/CFCs. Median AsBR and AjBR were both 2.2 with BPA/CFC prophylaxis and 0.0 in the fitusiran efficacy period. Two participants (3.0%) experienced suspected or confirmed thromboembolic events with fitusiran. Once-monthly fitusiran prophylaxis significantly reduced bleeding events vs BPA/CFC prophylaxis in PwHA/B, with or without inhibitors, and reported adverse events were generally consistent with previously identified risks of fitusiran. This trial was registered at www.ClinicalTrials.gov as #NCT03549871.
Vector integration and fate in the hemophilia dog liver multiple years after AAV-FVIII gene transfer
Authors: Batty Paul , Fong Sylvia , Franco Matteo , Sihn Choong-Ryoul , Swystun Laura L. , Afzal Saira , Harpell Lorianne , Hurlbut David , Pender Abbey , Su Cheng , Thomsen Hauke , Wilson Christopher , Youssar Loubna , Winterborn Andrew , Gil-Farina Irene , Lillicrap David 
Published: March 2024

Abstract
Gene therapy using adeno-associated virus (AAV) vectors is a promising approach for the treatment of monogenic disorders. Long-term multiyear transgene expression has been demonstrated in animal models and clinical studies. Nevertheless, uncertainties remain concerning the nature of AAV vector persistence and whether there is a potential for genotoxicity. Here, we describe the mechanisms of AAV vector persistence in the liver of a severe hemophilia A dog model (male = 4, hemizygous; and female = 4, homozygous), more than a decade after portal vein delivery. The predominant vector form was nonintegrated episomal structures with levels correlating with long-term transgene expression. Random integration was seen in all samples (median frequency, 9.3e−4 sites per cell), with small numbers of nonrandom common integration sites associated with open chromatin. No full-length integrated vectors were found, supporting predominant episomal vector-mediated long-term transgene expression. Despite integration, this was not associated with oncogene upregulation or histopathological evidence of tumorigenesis. These findings support the long-term safety of this therapeutic modality.
Nilotinib with or without cytarabine for Philadelphia-positive acute lymphoblastic leukemia
Authors: Chalandon Yves , Rousselot Philippe , Chevret Sylvie , Cayuela Jean-Michel , Kim Rathana , Huguet Françoise , Chevallier Patrice , Graux Carlos , Thiebaut-Bertrand Anne , Chantepie Sylvain , Thomas Xavier , Vincent Laure , Berthon Céline , Hicheri Yosr , Raffoux Emmanuel , Escoffre-Barbe Martine , Plantier Isabelle , Joris Magalie , Turlure Pascal , Pasquier Florence , Belhabri Amine , Guepin Gabrielle Roth , Blum Sabine , Gregor Michael , Lafage-Pochitaloff Marina , Quessada Julie , Lhéritier Véronique , Clappier Emmanuelle , Boissel Nicolas , Dombret Hervé 
Published: March 2024

Abstract
We previously demonstrated that a reduced-intensity chemotherapy schedule can safely replace hyper-CVAD (cyclophosphamide-vincristine-doxorubicin [Adriamycin]-dexamethasone) cycle 1 when combined with imatinib in adults with Philadelphia-positive acute lymphoblastic leukemia. In the present randomized GRAAPH-2014 trial, we used nilotinib and addressed the omission of cytarabine (Ara-C) in consolidation. The primary objective was the major molecular response (MMR) rate measured by BCR::ABL1 quantification after cycle 4 (end of consolidation). All patients were eligible for allogeneic stem cell transplant (SCT), whereas those in MMR could receive autologous SCT, followed by 2-year imatinib maintenance in both cases. After the enrollment of 156 of 265 planed patients, the data and safety monitoring board decided to hold the randomization because of an excess of relapse in the investigational arm. Among the 155 evaluable patients, 76 received Ara-C during consolidation (arm A) and 79 did not (arm B). Overall, 133 patients (85%) underwent SCT, 93 allogeneic and 40 autologous. The noninferiority end point regarding MMR was reached with 71.1% (arm A) and 77.2% (arm B) of patients reaching MMR. However, the 4-year cumulative incidence of relapse was higher in arm B compared with arm A (31.3% [95% confidence interval {CI}, 21.1%-41.9%] vs 13.2% [95% CI, 6.7%-21.9%]; P = .017), which translated to a lower relapse-free survival. With a median follow-up of 3.8 years, 4-year overall survival was 79.0% (95% CI, 70.6%-89.3%) in arm A vs 73.4% (95% CI, 63.9%-84.4%) in arm B (P = .35). Despite a noninferior rate of MMR, more relapses were observed when ARA-C was omitted without impact on survival. ClinicalTrials.gov ID, NCT02611492.
Cardiopulmonary exercise testing and body composition
Authors: Karlsson Per , Lind Lars , Michaëlsson Karl , Malinovschi Andrei 
Published: March 2024

BackgroundThe cardiopulmonary exercise test (CPET) evaluates cardiopulmonary function. In light of the obesity epidemic, it is important to understand how body composition affects interpretation of CPET results. The aim of the present study was to assess the relationship between CPET measures, other than peak oxygen uptake, and body composition.MethodA total of 330 participants, aged 50 years, performed both a CPET and dual-energy X-ray absorptiometry (DXA). From the CPET, peak exercise respiratory exchange ratio (RER), ventilatory efficiency (V̇E/V̇CO2slope) and work efficiency (ΔV̇O2/ΔWR) were recorded. Pearson's correlation was used to assess the association between CPET measures and selected body composition measures, including body mass index (BMI), waist circumference, fat mass, lean mass, body fat percentage and percentage trunk fat to fat mass. All analyses were done stratified by sex. A p-value <0.05 defined statistical significance.ResultsRER was negatively correlated with body composition measures; the strongest correlation was observed with waist circumference in females (r= −0.36).V̇E/V̇CO2slope had no significant correlations with any body composition measures. ΔV̇O2/ΔWR was positively correlated with the body composition measures; the strongest correlation was observed with BMI (r=0.24). The additive role of percentage body fat and percentage trunk fat were studied in a linear regression model using waist circumference and BMI to predict the aforementioned CPET measures and no additive role was found.ConclusionRER and ΔV̇O2/ΔWR may be influenced by body composition whileV̇E/V̇CO2slope is not affected. Adiposity measures from DXA add no additional explanatory value to the CPET measures.