bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicentre, interventional, single-arm study protocol of telemonitored circadian rhythms and patient-reported outcomes for improving mFOLFIRINOX safety in patients with pancreatic cancer (MultiDom, NCT04263948)
Authors: Bouchahda Mohamed , Ulusakarya Ayhan , Thirot-Bidault Anne , Attari Amal , Bossevot Rachel , Tuligenga Richard , Hammel Pascal , Adam René , Levi Francis 
Published: June 2023

IntroductionCircadian clocks regulate cellular proliferation and drug effects. Tolerability and/or efficacy of anticancer therapies have been improved by their administration according to circadian rhythms, while being predicted by circadian robustness. The combination of leucovorin, fluorouracil, irinotecan and oxaliplatin (mFOLFIRINOX) is a standard treatment for pancreatic ductal adenocarcinoma (PDAC), that generates grades 3–4 adverse events in the majority of patients and an estimated 15%–30% emergency admission rate. The MultiDom study evaluates whether mFOLFIRINOX safety can be improved using a novel circadian-based telemonitoring-telecare platform in patients at home. The detection of early warning signals of clinical toxicities could guide their early management, possibly preventing emergency hospital admissions.Methods and analysisThis multicentre, interventional, prospective, longitudinal, single-arm study hypothesises that the mFOLFIRINOX-related emergency admission rate will be 5% (95% CI 1.7% to 13.7%), among 67 patients with advanced PDAC. Study participation is 7 weeks for each patient, including a reference week before chemotherapy onset and 6 weeks afterwards. Accelerometry and body temperature are measured q1-min using a continuously worn telecommunicating chest surface sensor, daily body weight is self-measured with a telecommunicating balance and 23 electronic patient-reported outcomes (e-PROs) are self-rated using a tablet. Hidden Markov model, spectral analyses and other algorithms automatically compute physical activity, sleep, temperature, body weight change, e-PRO severity and 12 circadian sleep/activity parameters, including the dichotomy index I<O (% activity ‘in-bed’ below median activity ‘out-of-bed’), once to four times daily. Health professionals access visual displays of near-real time parameter dynamics and receive automatic alerts, with trackable digital follow-up.Ethics and disseminationThe study has been approved by the National Agency for Medication and Health Product Safety (ANSM) and Ethics Committee West V (2 July 2019; third amendment, 14 June 2022). The data will be disseminated at conferences and in peer-reviewed journals and will support large-scale randomised evaluation.Trial registration numbersNCT04263948and ID RCB-2019-A00566-51.
Efficacy of alcohol reduction interventions among people with HIV as evaluated by self-report and a phosphatidylethanol (PEth) outcome: protocol for a systematic review and individual participant data meta-analysis
Authors: Kane Jeremy C , Allen Isabel , Fatch Robin , Scheffler Aaron , Emenyonu Nneka , Puryear Sarah B , Chirayil Priya , So-Armah Kaku , Kahler Christopher W , Magidson Jessica F , Conroy Amy A , Edelman E Jennifer , Woolf-King Sarah , Parry Charles , Kiene Susan M , Chamie Gabriel , Adong Julian , Go Vivian F , Cook Robert L , Muyindike Winnie , Morojele Neo , Blokhina Elena , Krupitsky Evgeny , Fiellin David A , Hahn Judith A 
Published: June 2023

IntroductionUnhealthy alcohol use is associated with a range of adverse outcomes among people with HIV (PWH). Testing the efficacy and promoting the availability of effective interventions to address unhealthy alcohol use among PWH is thus a priority. Alcohol use outcomes in intervention studies are often measured by self-report alone, which can lead to spurious results due to information biases (eg, social desirability). Measuring alcohol outcomes objectively through biomarkers, such as phosphatidylethanol (PEth), in addition to self-report has potential to improve the validity of intervention studies. This protocol outlines the methods for a systematic review and individual participant data meta-analysis that will estimate the efficacy of interventions to reduce alcohol use as measured by a combined categorical self-report/PEth variable among PWH and compare these estimates to those generated when alcohol is measured by self-report or PEth alone.Methods and analysisWe will include randomised controlled trials that: (A) tested an alcohol intervention (behavioural and/or pharmacological), (B) enrolled participants 15 years or older with HIV; (C) included both PEth and self-report measurements, (D) completed data collection by 31 August 2023. We will contact principal investigators of eligible studies to inquire about their willingness to contribute data. The primary outcome variable will be a combined self-report/PEth alcohol categorical variable. Secondary outcomes will include PEth alone, self-report alone and HIV viral suppression. We will use a two-step meta-analysis and random effects modelling to estimate pooled treatment effects; I2will be calculated to evaluate heterogeneity. Secondary and sensitivity analyses will explore treatment effects in adjusted models and within subgroups. Funnel plots will be used to explore publication bias.Ethics and disseminationThe study will be conducted with deidentified data from completed randomised controlled trials and will be considered exempt from additional ethical approval. Results will be disseminated through peer-reviewed publications and international scientific meetings.PROSPERO registration numberCRD42022373640.
Emergency cerclage using double-level versus single-level suture in the management of cervical insufficiency (Cervical Occlusion double-level Stitch Application,COSA): study protocol for a multicentre, non-blinded, randomised controlled trial
Authors: Kosińska Kaczyńska Katarzyna , Rebizant Beata , Bednarek Katarzyna , Dabrowski Filip Andrzej , Kajdy Anna , Muzyka-Placzyńska Katarzyna , Filipecka-Tyczka Dagmara , Uzar Piotr , Kwiatkowski Sebastian , Torbe Andrzej , Grzesiak Mariusz , Kaczmarek Piotr , Żyła Monika , Brawura-Biskupski-Samaha Robert 
Published: June 2023

IntroductionCervical insufficiency accounts for 15% of recurrent pregnancy losses between 16 and 28 weeks of gestation. The aim of the study is to verify the effectiveness of emergency double-level cerclage with vaginal progesterone in cervical insufficiency treatment in terms of the prevention of preterm delivery before 34 weeks of gestation.Methods and analysisThis trial is a multicentre, non-blinded, randomised study with 1:1 allocation ratio. The study is conducted at tertiary perinatal care departments in Poland. It will include patients with cervical insufficiency with the fetal membranes visible in the open cervical canal or protruding into the vagina between 16+0 and 23+6 weeks of pregnancy. They will be randomised into two arms: emergency single-level cerclage with vaginal progesterone or double-level cerclage with vaginal progesterone. All will be administered antibiotics and indomethacin. The primary outcome is the rate of deliveries below 34+0 weeks of gestation, while secondary outcomes include gestational age at delivery, neonatal outcomes, maternal outcomes according to the Core Outcome Set for Evaluation of Interventions to Prevent Preterm Birth and cerclage procedure complications. The planned number of participants according to the power analysis is 78.Ethics and disseminationThe study protocol was written in accordance with the Standard Protocol Items: Recommendations for Interventional Trials statement. It was created according to the requirements of the Declaration of Helsinki for Medical Research involving Human Subject. Ethical approval was obtained from the Ethics Committee of the Centre of Postgraduate Medical Education (no. 1/2022). The study protocol was approved and published by ClinicalTrials.gov (posted on 24 February 2022). All participants gave a written informed consent. After completion of the study its results will be published in a peer-reviewed English language journal.Trial registrationNCT05268640.
Effect of plant milk consumption on childhood growth: protocol for a systematic review
Authors: Soczynska Izabela , da Costa Bruno R , O'Connor Deborah L , Jenkins David J A , Birken Catherine S , Keown-Stoneman Charles D G , D'Hollander Curtis , Calleja Sabine , Maguire Jonathon L 
Published: June 2023

IntroductionThere has been considerable debate about whether plant milks can support the nutritional requirements of growing children. The proposed systematic review aims to assess the evidence on the relationship between plant milk consumption and growth and nutritional status in childhood.Methods and analysisOvid MEDLINE ALL (1946–present), Ovid EMBASE Classic (1947–present), CINAHL Complete (Cumulative Index to Nursing and Allied Health Literature), Scopus, the Cochrane Library and grey literature will be searched comprehensively (from 2000 to present; English language) to find studies that describe the association between plant milk consumption and growth or nutrition in children 1–18 years of age. Two reviewers will identify eligible articles, extract data and assess the risk of bias in individual studies. If a meta-analyses is not conducted, the evidence will be synthesised narratively and the overall certainty of evidence will be rated using the Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and disseminationEthical approval is not required for this study since no data will be collected. Results of the systematic review will be published in a peer-reviewed journal. Findings from this study may be useful in informing future evidence-based recommendations about plant milk consumption in children.PROSPERO registration numberCRD42022367269.
Novel risk score for acute upper gastrointestinal bleeding in elderly patients: a single-centre retrospective study
Authors: Li Yajie , Lu Qin , Song Mingyang , Wu Kexuan , Ou Xilong 
Published: June 2023

ObjectivesAcute upper gastrointestinal bleeding (UGIB) is a common reason for emergency hospital admission. Identifying low-risk patients suitable for outpatient management is a clinical and research priority. This study aimed to develop a simple risk score to identify elderly patients with UGIB for whom hospital admission is not required.DesignThis was a single-centre retrospective study.SettingThis study was conducted at Zhongda Hospital affiliated with Southeast University in China.ParticipantsPatients from January 2015 to December 2020 for the derivation cohort and from January 2021 to June 2022 for the validation cohort were enrolled in this study. A total of 822 patients (derivation cohort=606 and validation cohorts=216) were included in this study. Patients aged ≥65 years with coffee-grounds vomiting, melena or/and haematemesis were included in the analysis. Patients admitted but had UGIB or transferred between hospitals were excluded.MethodsBaseline demographic characteristics and clinical parameters were recorded at the first visit. Data were collected from electronic records and databases. Multivariable logistic regression modelling was performed to identify predictors of safe discharge.Results304/606 (50.2%) and 132/216 (61.1%) patients were not safely discharged in the derivation and validation cohorts, respectively. A clinical risk score of five variables was entered into UGIB risk stratification: Charlson Comorbidity Index >2, systolic blood pressure <100 mm Hg, haemoglobin <100 g/L, blood urea nitrogen ≥6.5 mmol/L, albumin <30 g/L. The optimal cut-off value was ≥1, the sensitivity was 97.37% and the specificity was 19.21% for predicting the inability to discharge safely. The area under the receiver operating characteristic curve was 0.806.ConclusionsA novel clinical risk score with good discriminative performance was developed to identify elderly patients with UGIB who were suitable for safe outpatient management. This score can reduce unnecessary hospitalisations.
Efficacy of autologous plateletpheresis in adult aortic surgery: study protocol for a randomised controlled trial
Authors: Gao Jie , Jia Jinna , Gao Xurong , Ji Hongwen 
Published: June 2023

IntroductionPerioperative coagulopathy is common in patients undergoing aortic surgery, increasing the risk of excessive blood loss and subsequent allogeneic transfusion. Blood conservation has become a vital part of cardiovascular surgery, but measures to protect platelets from destruction by cardiopulmonary bypass (CPB) are still lacking. Autologous platelet concentrate (APC) may have potential benefits for intraoperative blood preservation, but its efficacy has not been studied extensively. This study aims to evaluate the efficacy of APC as a blood conservation technique to reduce blood transfusion in adult aortic surgery.Methods and analysisThis is a prospective, single-centre, single-blind randomised controlled trial. A total of 344 adult patients undergoing aortic surgery with CPB will be enrolled and randomised to either the APC group or the control group with a 1:1 randomisation ratio. Patients in the APC group will receive autologous plateletpheresis before heparinisation, while those in the control group will not. The primary outcome is the perioperative packed red blood cell (pRBC) transfusion rate. Secondary endpoints include the volume of perioperative pRBC transfusion; drainage volume within 72 hours post-surgery; postoperative coagulation and platelet function; and the incidence of adverse events. Data will be analysed according to the intention-to-treat principle.Ethics and disseminationThis study was approved by the institutional review board of Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (no. 2022-1806). All procedures included in this study will be performed in adherence to the Helsinki Declaration. The results of the trial will be published in an international peer-reviewed journal.Trial registration numberChinese Clinical Trial Register (ChiCTR2200065834).
Learning from experience: a qualitative study of surgeons’ perspectives on reporting and dealing with serious adverse events
Authors: Øyri Sina Furnes , Søreide Kjetil , Søreide Eldar , Tjomsland Ole 
Published: June 2023

IntroductionIn surgery, serious adverse events have effects on the patient journey, the patient outcome and may constitute a burden to the surgeon involved. This study aims to investigate facilitators and barriers to transparency around, reporting of and learning from serious adverse events among surgeons.MethodsBased on a qualitative study design, we recruited 15 surgeons (4 females and 11 males) with 4 different surgical subspecialties from four Norwegian university hospitals. The participants underwent individual semistructured interviews and data were analysed according to principles of inductive qualitative content analysis.Results and discussionWe identified four overarching themes. All surgeons reported having experienced serious adverse events, describing these as part of ‘the nature of surgery’. Most surgeons reported that established strategies failed to combine facilitation of learning with taking care of the involved surgeons. Transparency about serious adverse events was by some felt as an extra burden, fearing that openness on technical-related errors could affect their future career negatively. Positive implications of transparency were linked with factors such as minimising the surgeon’s feeling of personal burden with positive impact on individual and collective learning. A lack of facilitation of individual and structural transparency factors could entail ‘collateral damage’. Our participants suggested that both the younger generation of surgeons in general, and the increasing number of women in surgical professions, might contribute to ‘maturing’ the culture of transparency.Conclusion and implicationsThis study suggests that transparency associated with serious adverse events is hampered by concerns at both personal and professional levels among surgeons. These results emphasise the importance of improved systemic learning and the need for structural changes; it is crucial to increase the focus on education and training curriculums and offer advice on coping strategies and establish arenas for safe discussions after serious adverse events.
Young persons and healthcare professionals experience of virtual gastroenterology consultations: a multicentre survey conducted during the COVID-19 pandemic
Authors: Hubbard Rhona , Brooks Alenka , Arebi Naila , El-Khouly Sara , Kiparissi Fevronia , Mozdiak Ella , Muhammed Rafeeq , Smith Philip J , Zarate-Lopez Natalia , Garrick Victoria , Greenan-Barrett James , Baker Sarah , Bradbury Keith , DelNero Nicholas , Narula Priya 
Published: June 2023

ObjectiveTo explore Young Persons (YP) and healthcare professionals (HCP) experiences of virtual consultations (VC) and establish whether developmentally appropriate healthcare can be delivered virtually.MethodYP and HCP questionnaire surveys were designed and piloted. Electronic questionnaire links were sent by post, email or text message January–April 2021 to YP aged 13–25 years old, with predefined chronic gastrointestinal conditions, attending a gastroenterology/hepatology VC. HCP undertaking VC were invited to complete staff questionnaire. Results were anonymous and collated using Excel version 2302.ResultsFive UK hospital trusts participated, with 35 HCP responses. Of the 100 YP completing the survey 66% were female and 34% male aged between 13 years and 25 years (median: 18 years). 13% were new appointments and 87% follow ups, 29% were by video, 69% by phone and 2% gave no response. 80% of HCP spoke to YP directly but not privately (69%). 87% of YP and 88% HCP found VC useful. 83% of YP want VC again, although 20% preferred face to face. 43% of HCP required improved phone/internet connection. 77% of YP required hospital appointments for tests following VC.ConclusionsOverall respondents were satisfied with VC, finding them useful, convenient and time saving. Successful VC rely on appropriate patient selection and availability of reliable technology. Patient preference is key which may alter with time.
Early decrease of blood myeloid-derived suppressor cells during checkpoint inhibition is a favorable biomarker in metastatic melanoma
Authors: Gaißler Andrea , Bochem Jonas , Spreuer Janine , Ottmann Shannon , Martens Alexander , Amaral Teresa , Wagner Nikolaus Benjamin , Claassen Manfred , Meier Friedegund , Terheyden Patrick , Garbe Claus , Eigentler Thomas , Weide Benjamin , Pawelec Graham , Wistuba-Hamprecht Kilian 
Published: June 2023

BackgroundThe need for reliable clinical biomarkers to predict which patients with melanoma will benefit from immune checkpoint blockade (ICB) remains unmet. Several different parameters have been considered in the past, including routine differential blood counts, T cell subset distribution patterns and quantification of peripheral myeloid-derived suppressor cells (MDSC), but none has yet achieved sufficient accuracy for clinical utility.MethodsHere, we investigated potential cellular biomarkers from clinical routine blood counts as well as several myeloid and T cell subsets, using flow cytometry, in two independent cohorts of a total of 141 patients with stage IV M1c melanoma before and during ICB.ResultsElevated baseline frequencies of monocytic MDSCs (M-MDSC) in the blood were confirmed to predict shorter overall survival (OS) (HR 2.086, p=0.030) and progression-free survival (HR 2.425, p=0.001) in the whole patient cohort. However, we identified a subgroup of patients with highly elevated baseline M-MDSC frequencies that fell below a defined cut-off during therapy and found that these patients had a longer OS that was similar to that of patients with low baseline M-MDSC frequencies. Importantly, patients with high M-MDSC frequencies exhibited a skewed baseline distribution of certain other immune cells but these did not influence patient survival, illustrating the paramount utility of MDSC assessment.ConclusionWe confirmed that in general, highly elevated frequencies of peripheral M-MDSC are associated with poorer outcomes of ICB in metastatic melanoma. However, one reason for an imperfect correlation between high baseline MDSCs and outcome for individual patients may be the subgroup of patients identified here, with rapidly decreasing M-MDSCs on therapy, in whom the negative effect of high M-MDSC frequencies was lost. These findings might contribute to developing more reliable predictors of late-stage melanoma response to ICB at the individual patient level. A multifactorial model seeking such markers yielded only MDSC behavior and serum lactate dehydrogenase as predictors of treatment outcome.
Prevalence of pulmonary hypertension in mitral regurgitation and its influence on outcomes
Authors: Ratwatte Seshika , Strange Geoff , Playford David , Stewart Simon , Celermajer David S 
Published: June 2023

ObjectivePulmonary hypertension (PHT) commonly coexists with significant mitral regurgitation (MR), but its prevalence and prognostic importance have not been well characterised. In a large cohort of adults with moderate or greater MR, we aimed to describe the prevalence and severity of PHT and assess its influence on outcomes.MethodsIn this retrospective study, we analysed the National Echocardiography Database of Australia (data from 2000 to 2019). Adults with an estimated right ventricular systolic pressure (eRVSP), left ventricular ejection fraction >50% and with moderate or greater MR were included (n=9683). These subjects were then categorised according to their eRVSP. The relationship between PHT severity and mortality outcomes was evaluated (median follow-up of 3.2 years, IQR 1.3–6.2 years).ResultsSubjects were aged 76±12 years, and 62.6% (6038) were women. Overall, 959 (9.9%) had no PHT, and 2952 (30.5%), 3167 (32.7%), 1588 (16.4%) and 1017 (10.5%) patients had borderline, mild, moderate and severe PHT, respectively. A ‘typical left heart disease’ phenotype was identified with worsening PHT, showing rising E:e′, right and left atrial sizes increasing progressively, from no PHT to severe PHT (p<0.0001, for all). With increasing PHT severity, 1- and 5-year actuarial mortality increased from 8.5% and 33.0% to 39.7% and 79.8%, respectively (p<0.0001). Similarly, adjusted survival analysis showed the risk of long-term mortality progressively increased with higher eRVSP levels (adjusted HR 1.20–2.86, borderline to severe PHT, p<0.0001 for all). A mortality inflection was apparent at an eRVSP level >34.00 mm Hg (HR 1.27, CI 1.00–1.36).ConclusionsIn this large study, we report on the importance of PHT in patients with MR. Mortality increases as PHT becomes more severe from an eRVSP of 34 mm Hg onwards.