bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frail2Fit study protocol: a feasibility and acceptability study of a virtual multimodal intervention delivered by volunteers to improve functional outcomes in older adults with frailty after discharge from hospital
Authors: Meredith Samantha Jane , Roberts Helen , Grocott Michael P W , Jack Sandy , Murphy Jane , Varkonyi-Sepp Judit , Bates Andrew , Lim Stephen Eu Ruen 
Published: March 2023

IntroductionPhysical activity (PA) and replete nutritional status are key to maintaining independence and improving frailty status among frail older adults. In response to the COVID-19 pandemic, healthcare has increasingly turned to virtual modes of delivery and there is interest in the use of trained volunteers to deliver PA and nutrition interventions. We aim to evaluate the feasibility and acceptability of training hospital volunteers to deliver an online intervention, comprising exercise, behaviour change and nutrition support, to older people with frailty after discharge from hospital.MethodsWe will use a quasi-experimental mixed methods approach. Hospital volunteers (n=6) will be trained to deliver an online, 3-month, multimodal intervention to frail (Clinical Frailty Scale ≥5) adults ≥65 years (n=30) after discharge from hospital. Feasibility will be assessed by determining the number of volunteers recruited, trained and retained at the end of the study; the proportion of intervention sessions delivered; participant recruitment, retention and adherence to the intervention. To determine the acceptability of the intervention, interviews will be conducted among a purposive sample of older adults, and volunteers. Secondary outcomes will include physical function, appetite, well-being, quality of life, anxiety and depression, self-efficacy for managing chronic disease and PA. Outcomes will be measured at baseline, 3 months and 6 months.AnalysisDescriptive statistics will be used to describe feasibility and adherence to the intervention. Secondary outcomes at baseline will be compared at 3 and 6 months. Interviews will be transcribed verbatim and analysed using thematic analysis.Ethics and disseminationHealth Research Authority ethical approval was obtained on 30 May 2022 (reference: 22/WA/0155). Results will be disseminated through peer-reviewed journal articles, volunteer organisations, National Health Service communication systems and social media platforms. A toolkit will be developed to facilitate roll out of volunteer training.Trial registration numberNCT05384730.
Reducing incidence of postoperative acute kidney injury in trauma and orthopaedics patients: a quality improvement project
Authors: Kulkarni Sanat , Richardson Thomas , Green Alice , Acharya Radhika , Latif Arusa , Johnson Dakota , Naqvi Huma , Gella Sreenadh 
Published: March 2023

BackgroundAcute kidney injury (AKI) is a common postoperative complication which increases morbidity and mortality. This quality improvement project aimed to implement measures targeting known risk factors to decrease the incidence of postoperative AKI in trauma and orthopaedics (T&O) patients.MethodsData were collected across three six-month to 7-month cycles between 2017 and 2020, analysing all elective and emergency T&O operated patients within a single NHS Trust (n=714, 1008 and 928, respectively). Patients who developed a postoperative AKI were identified using biochemical criteria and data were collected on known AKI risk factors, including use of nephrotoxic medications, and patient outcomes. In the final cycle, the same variables were collected for patients without AKI. Between cycles, measures implemented included: preoperative and postoperative medication reconciliation aiming to stop nephrotoxic medications, orthogeriatrician review of high-risk patients and junior doctor teaching on fluid therapy. Statistical analysis was undertaken to determine the incidence of postoperative AKI across cycles, prevalence of risk factors and impact on length of hospital stay and postoperative mortality.ResultsThere was a statistically significant decrease in postoperative AKI incidence from 4.27% (43 of 1008 patients) in cycle 2 to 2.05% (19 of 928) in cycle 3 (p=0.006), with a notable decrease in use of nephrotoxic medications. Significant predictors for the development of postoperative AKI included use of diuretics and receiving multiple nephrotoxic drug classes. Development of postoperative AKI significantly increased length of hospital stay by 7.11 days on average (95% CI: 4.84 to 9.38 days, p<0.001) and risk of 1-year postoperative mortality (OR 3.22, 95% CI: 1.03 to 10.55, p=0.046).ConclusionThis project demonstrates that a multifaceted approach targeting modifiable risk factors can reduce incidence of postoperative AKI in T&O patients, which may lead to reduced length of hospital stay and postoperative mortality.
Assessing and investigating children with suspected bone and abdominal tumours: an e-Delphi consensus process
Authors: Shanmugavadivel Dhurgshaarna , Liu Jo-Fen , Gamble Ashley , Polanco Angela , Vedhara Kavita , Walker David , Ojha Shalini 
Published: March 2023

BackgroundThe incidence of childhood cancer has risen by 15% since the 1990s. Early diagnosis is key to optimising outcomes, however diagnostic delays are widely reported. Presenting symptoms are often non-specific causing a diagnostic dilemma for clinicians. This Delphi consensus process was conducted to develop a new clinical guideline for children and young people presenting with signs/symptoms suggestive of a bone or abdominal tumour.MethodsInvitation emails were sent to primary and secondary healthcare professionals to join the Delphi panel. 65 statements were derived from evidence review by a multidisciplinary team. Participants were asked to rank their level of agreement with each statement on a 9-point Likert scale (1=strongly disagree, 9=strongly agree), with responses ≥7 taken to indicate agreement. Statements not reaching consensus were rewritten and reissued in a subsequent round.ResultsAll statements achieved consensus after two rounds. 96/133 (72%) participants responded to round 1 (R1) and 69/96 (72%) completed round 2 (R2). 62/65 (94%) statements achieved consensus in R1 with 29/65 (47%) gaining more than 90% consensus. Three statements did not reach consensus scoring between 61% and 69%. All reached numerical consensus at the end of R2. Strong consensus was reached on best practice of conducting the consultation, acknowledging parental instinct and obtaining telephone advice from a paediatrician to decide the timing and place of review, rather than adult cancer urgent referral pathways. Dissensus in statements was due to unachievable targets within primary care and valid concerns over a potential overinvestigation of abdominal pain.ConclusionsThis consensus process has consolidated statements that will be included in a new clinical guideline for suspected bone and abdominal tumours for use in both primary and secondary care. This evidence base will be translated into awareness tools for the public as part of the Child Cancer Smart national awareness campaign.
Exploring the appropriateness of prescribing practice of inhaled pharmacotherapy among Aboriginal Australians in the Top End Northern Territory of Australia: a retrospective cohort study
Authors: Heraganahally Subash , Howarth Timothy P , Issac Siji , Lloyd Angus , Ravichandran Shiidheshwar J , Abeyaratne Asanga , Patel Bhavini 
Published: March 2023

BackgroundAboriginal Australians are reported to have a high burden of chronic airway diseases. However, prescribing patterns and related outcomes of airway directed inhaled pharmacotherapy, (short-acting beta agonists (SABA), short-acting muscarinic antagonists (SAMA), long-acting β-agonists (LABA), long-acting muscarinic antagonists (LAMA) and inhaled corticosteroids (ICS)) among Aboriginal Australian patients with chronic airway disease have been sparsely reported in the past.MethodsA retrospective cohort study was conducted, using clinical, spirometry data, chest radiology, primary healthcare (PHC) presentations and hospital admission rates among Aboriginal patients identified to have been prescribed inhaled pharmacotherapy in remote and rural communities referred to the respiratory specialist service in the Top End, Northern Territory of Australia.ResultsOf the 372 identified active patients, 346 (93%) had inhaled pharmacotherapy prescribed (64% female, median age 57.7 years). ICS was the most common prescription (72% of the total cohort) and was recorded to be prescribed in 76% of patients with bronchiectasis, and 80% of patients with asthma or chronic obstructive pulmonary disease (COPD). Fifty-eight percent of patients had a respiratory hospital admission and 57% had a recorded PHC presentation for a respiratory issue during the study period, with a higher rate of hospital admissions among patients prescribed ICS compared with those on SAMA/SABA or LAMA/LABA without ICS (median rate (per person per year) 0.42 vs 0.21 and 0.21 (p=0.004). Regression models demonstrated that presence of COPD or bronchiectasis alongside ICS was associated with significantly increased hospitalisation rates (1.01 admissions/person/year (95% CI 0.15 to 1.87) and 0.71 admissions/person/year (95% CI 0.23 to 1.18) against patients without COPD/bronchiectasis, respectively).ConclusionsThis study demonstrates that among Aboriginal patients with chronic airway diseases, ICS is the most common inhaled pharmacotherapy prescribed. Although LAMA/LABA and concurrent ICS use may be appropriate among patients with asthma and COPD, the use of ICS may have detrimental effects among those with underlying bronchiectasis either in isolation or concurrent COPD and bronchiectasis, potentially leading to higher hospital admission rates.
Effects of a home-based, exergaming intervention on physical function and pain after total knee replacement in older adults: a randomised controlled trial
Authors: Janhunen Maarit , Katajapuu Niina , Paloneva Juha , Pamilo Konsta , Oksanen Airi , Keemu Hannes , Karvonen Mikko , Luimula Mika , Korpelainen Raija , Jämsä Timo , Kautiainen Hannu , Mäkelä Keijo , Heinonen Ari , Aartolahti Eeva 
Published: March 2023

ObjectivesTo investigate the effects of 4 months of customised, home-based exergaming on physical function and pain after total knee replacement (TKR) compared with standard exercise protocol.MethodsIn this non-blinded randomised controlled trial, 52 individuals aged 60–75 years undergoing TKR were randomised into an exergaming (intervention group, IG) or a standard exercising group (control group, CG). Primary outcomes were physical function and pain measured before and after (2 months and 4 months) surgery using the Oxford Knee Score (OKS) and Timed Up and Go (TUG) test. Secondary outcomes included measures of the Visual Analogue Scale, 10m walking, short physical performance battery, isometric knee extension and flexion force, knee range of movement and satisfaction with the operated knee.ResultsImprovement in mobility measured by TUG was greater in the IG (n=21) at 2 (p=0.019) and 4 months (p=0.040) than in the CG (n=25). The TUG improved in the IG by −1.9 s (95% CI, −2.9 to −1.0), while it changed by −0.6 s (95% CI −1.4 to 0.3) in the CG. There were no differences between the groups in the OKS or secondary outcomes over 4 months. 100% of patients in the IG and 74% in the CG were satisfied with the operated knee.ConclusionIn patients who have undergone TKR, training at home with customised exergames was more effective in mobility and early satisfaction and as effective as standard exercise in pain and other physical functions. In both groups, knee-related function and pain improvement can be considered clinically meaningful.Trial registration numberNCT03717727.
One-year quality-of-life outcomes of cardiac arrest survivors by initial defibrillation provider
Authors: Haskins Brian , Nehme Ziad , Andrew Emily , Bernard Stephen , Cameron Peter , Smith Karen 
Published: March 2023

ObjectiveTo assess the long-term functional and health-related quality-of-life (HRQoL) outcomes for out-of-hospital cardiac arrest (OHCA) survivors stratified by initial defibrillation provider.MethodsThis retrospective study included adult non-traumatic OHCA with initial shockable rhythms between 2010 and 2019. Survivors at 12 months after arrest were invited to participate in structured telephone interviews. Outcomes were identified using the Glasgow Outcome Scale-Extended (GOS-E), EuroQol-5 Dimension (EQ-5D), 12-Item Short Form Health Survey and living and work status-related questions.Results6050 patients had initial shockable rhythms, 3211 (53.1%) had a pulse on hospital arrival, while 1879 (31.1%) were discharged alive. Bystander defibrillation using the closest automated external defibrillator had the highest survival rate (52.8%), followed by dispatched first responders (36.7%) and paramedics (27.9%). 1802 (29.8%) patients survived to 12-month postarrest; of these 1520 (84.4%) were interviewed. 1088 (71.6%) were initially shocked by paramedics, 271 (17.8%) by first responders and 161 (10.6%) by bystanders. Bystander-shocked survivors reported higher rates of living at home without care (87.5%, 75.2%, 77.0%, p<0.001), upper good recovery (GOS-E=8) (41.7%, 30.4%, 30.6%, p=0.002) and EQ-5D visual analogue scale (VAS) ≥80 (64.9%, 55.9%, 52.9%, p=0.003) compared with first responder and paramedics, respectively. After adjustment, initial bystander defibrillation was associated with higher odds of EQ-5D VAS ≥80 (adjusted OR (AOR) 1.56, 95% CI 1.15–2.10; p=0.004), good functional recovery (GOS-E ≥7) (AOR 1.53, 95% CI 1.12–2.11; p=0.009), living at home without care (AOR 1.77, 95% CI 1.16–2.71; p=0.009) and returning to work (AOR 1.72, 95% CI 1.05–2.81; p=0.031) compared with paramedic defibrillation.ConclusionSurvivors receiving initial bystander defibrillation reported better functional and HRQoL outcomes at 12 months after arrest compared with those initially defibrillated by paramedics.
Elective ascending aortic aneurysm repair outcomes in a nationwide US cohort
Authors: Beyer Sebastian E , Secemsky Eric A , Khabbaz Kamal , Carroll Brett J 
Published: March 2023

ObjectiveTo quantify contemporary outcomes following elective ascending aortic aneurysm repair, to determine risk factors for adverse events and to evaluate difference by institutional surgical volume.MethodsWe included all elective hospitalisations of adult patients with an ascending aortic aneurysm who underwent aneurysm repair in the Nationwide Readmissions Database between 2016 and 2019. The primary outcome was a composite of in-hospital mortality, stroke (ischaemic and non-ischaemic) and myocardial infarction (MI). We identified independent predictor of adverse events and investigated outcomes by institutional volume.ResultsAmong 12 043 patients (mean 62.8 years of age, 28.0% female), MI, stroke or in-hospital death occurred in 598 (4.9%) patients during the index admission (acute stroke: 2.7%, MI: 0.7%, in-hospital death: 2.0%). The strongest predictors of in-hospital death, stroke or MI were chronic weight loss, pulmonary circulation disorder and concomitant descending aortic surgery. Higher procedural volume was associated with a lower incidence of in-hospital death, stroke or MI (OR comparing the highest with the lowest tertile 0.71, 95% CI 0.57 to 0.87; p=0.001) and in-hospital death (OR 0.51, 95% CI 0.37 to 0.72; p<0.001), but no difference in 30-day readmissions.ConclusionsThe overall rate of in-hospital death, stroke and MI is nearly 5% in patients undergoing elective ascending aortic aneurysm repair. Among several predictors, chronic weight loss is associated with the largest increase in the risk of poor outcomes. Higher hospital volume is associated with a lower in-hospital mortality, highlighting the importance to refer patients to high-volume centres while discussing the risks and benefits of proceeding with repair.
Effect of opioids for breathlessness in heart failure: a systematic review and meta-analysis
Authors: Gaertner Jan , Fusi-Schmidhauser Tanja , Stock Stephanie , Siemens Waldemar , Vennedey Vera 
Published: March 2023

BackgroundFor the treatment of breathlessness in heart failure (HF), most textbooks advocate the use of opioids. Yet, meta-analyses are lacking.MethodsA systematic review was performed for randomised controlled trials (RCTs) assessing effects of opioids on breathlessness (primary outcome) in patients with HF. Key secondary outcomes were quality of life (QoL), mortality and adverse effects. Cochrane Central Register of Controlled Trials, MEDLINE and Embase were searched in July 2021. Risk of bias (RoB) and certainty of evidence were assessed by the Cochrane RoB 2 Tool and Grading of Recommendations Assessment, Development and Evaluation criteria, respectively. The random-effects model was used as primary analysis in all meta-analyses.ResultsAfter removal of duplicates, 1180 records were screened. We identified eight RCTs with 271 randomised patients. Seven RCTs could be included in the meta-analysis for the primary endpoint breathlessness with a standardised mean difference of 0.03 (95% CI −0.21 to 0.28). No study found statistically significant differences between the intervention and placebo. Several key secondary outcomes favoured placebo: risk ratio of 3.13 (95% CI 0.70 to 14.07) for nausea, 4.29 (95% CI 1.15 to 16.01) for vomiting, 4.77 (95% CI 1.98 to 11.53) for constipation and 4.42 (95% CI 0.79 to 24.87) for study withdrawal. All meta-analyses revealed low heterogeneity (I2in all these meta-analyses was <8%).ConclusionOpioids for treating breathlessness in HF are questionable and may only be the very last option if other options have failed or in case of an emergency.PROSPERO registration numberCRD42021252201.
Evaluating the effectiveness of implementing a more severe law on prevention of road traffic injury mortality in mainland China: an interrupted time series study based on national mortality surveillance
Authors: Liu Jiangmei , Feng Xiaoqi , Steel David , Zhou Maigeng , Astell-Burt Thomas 
Published: March 2023

BackgroundIn China, road traffic injury (RTI) is the seventh-leading cause of death More than 1.5 million adults in China live with permanent disabilities due to road traffic accidents. In 2011, the Chinese government implemented a more severe law that increased the penalty points and fines for persons charged with drink-driving as a criminal offence.ObjectivesThis study evaluated the short-term and long-term effects of the drink-driving law. It also aimed to establish whether punishments of increased severity resulted in greater reductions in RTI mortality.MethodsRTI mortality data was obtained from the Disease Surveillance Points System. A two-level interrupted time series model was used to analyse daily and monthly road traffic mortality rates, accounting for the varying trends among counties.ResultsThe overall RTI mortality rate showed a decreasing trend from 2007 to 2015 in mainland China, especially after 2011, and similarly decreasing trends were noted among males and females and in urban and rural areas. After the Criminal Law and Road Traffic Law amendment was implemented in 2011, charging drink-driving as a criminal offence, the immediate daily RTI mortality rate reduced by 1.57% (RR=0.9843, 95% CI: 0.9444 to 1.0259), while the slope change significantly decreased by 0.04% (RR=0.9996, 95% CI: 0.9994 to 0.9997) compared with the period before the Law was revised. Stratified analysis showed that the effect size of the law was higher for males in urban and high socioeconomic circumstances (SEC) than females in rural and low and moderate SEC. Meanwhile, the increase in penalty points for dangerous driving behaviours showed no significant effects.ConclusionEvidence was found that charging criminal responsibility for drink-driving is associated with reducing RTI deaths in China.
An anti-mesothelin targeting antibody drug conjugate induces pyroptosis and ignites antitumor immunity in mouse models of cancer
Authors: Wittwer Nicole L , Staudacher Alexander H , Liapis Vasilios , Cardarelli Pina , Warren Harriet , Brown Michael P 
Published: March 2023

BackgroundEmerging evidence suggests that the mechanism of chemotherapy-induced cell death may influence the antitumor immune response in patients with cancer. Unlike immunologically silent apoptosis, pyroptosis is a lytic and inflammatory form of programmed cell death characterized by pore formation in the cell membrane and release of proinflammatory factors. Gasdermin E (GSDME) has recently gained attention after cleavage of GSDME by certain chemotherapeutics has been shown to elicit pyroptosis. This study investigated the immunomodulatory effects of a mesothelin-targeting antibody drug conjugate (ADC) in mouse models of breast and colon cancer.MethodsThe antitumor effects of the ADC were studied in EMT6 breast cancer and CT26 colon cancer syngeneic mouse models. The immunomodulatory effects of the ADC were assessed by analysis of tumor-infiltrating immune cells using flow cytometry. ADC mechanism of action was evaluated by morphology, biological assays, ADC-mediated cleavage of key effector proteins, and CRISPR/Cas9-mediated knockout (KO). Finally, the antitumor effect of ADC and Fms-like tyrosine kinase-3 ligand (Flt3L) combination therapy was evaluated in tumors expressing GSDME as well as in GSDME-silenced tumors.ResultsThe data demonstrated that the ADC controlled tumor growth and stimulated anticancer immune responses. Investigation of the mechanism of action revealed that tubulysin, the cytotoxic payload of the ADC, induced cleavage of GSDME and elicited pyroptotic cell death in GSDME-expressing cells. Using GSDME KO, we showed that GSDME expression is critical for the effectiveness of the ADC as a monotherapy. Combining the ADC with Flt3L, a cytokine that expands dendritic cells in both lymphoid and non-lymphoid tissues, restored control of GSDME KO tumors.ConclusionsTogether, these results show for the first time that tubulysin and a tubulysin containing ADC can elicit pyroptosis, and that this fiery cell death is critical for antitumor immunity and therapeutic response.