bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surveillance of indeterminate pulmonary nodules detected with CT in a Swedish population-based study (SCAPIS): psychosocial consequences and impact on health-related quality of life—a multicentre prospective cross-sectional study
Authors: Andersson Elisabeth , Dai Ydrefelt Ying , Johannesson Marit , Lundbäck Maria , Mannila Maria , Persson Margaretha , Swahn Eva , Bolejko Anetta 
Published: September 2021

ObjectivesTo investigate whether surveillance of pulmonary nodules detected with low-dose CT (LDCT) impacted health-related quality of life and psychosocial consequences in the Swedish population-based study, Swedish CArdioPulmonary bioImage Study (SCAPIS).DesignA prospective cross-sectional study.Settings and participantsThis multicentre (five sites) observational study, which included a cohort from SCAPIS, consisted of 632 participants with indeterminate pulmonary nodules detected with LDCT. These participants continued surveillance for up to 36 months, during which lung cancer was not detected (surveillance group). Additionally, 972 participants with a negative pulmonary LDCT scan were included as a control group. Matching criteria were LDCT date (±2 weeks), gender and site.Outcome measuresAll participants completed a health-related quality of life questionnaire (RAND-36) and the Consequences of Screening (COS) questionnaire, an average of 3 years after LDCT was conducted at entry into SCAPIS.ResultsParticipants were 51–70 years old at study commencement. Overall, the two groups did not differ in demographic or psychosocial variables, smoking habits or pulmonary medical history. Individuals from countries other than Sweden and those with low socioeconomic status were less likely to participate (p<0.001). No effects on health-related quality of life were observed via RAND-36. In COS, the surveillance group demonstrated a higher OR for anxiety about lung cancer (OR 3.96, 95% CI 2.35 to 6.66, p<0.001), experiencing a sense of dejection (OR 1.35, 95% CI 1.06 to 1.72, p=0.015) and thoughts about existential values (OR 1.30, 95% CI 1.04 to 1.60, p=0.018).ConclusionsLung surveillance with LDCT contributed to significant experiences of sense of dejection, anxiety about lung cancer and development of thoughts about existential values among participants in the surveillance group compared with the controls. The risk of side effects should be communicated for informed decision-making about (non-)attendance in lung cancer screening.
Identification and comparison of key criteria of feedback of funding decisions: mixed-methods analysis of funder and applicant perspectives
Authors: Fackrell Kathryn , Meadmore Katie , Recio-Saucedo Alejandra , Bull Abby , Fraser Simon , Blatch-Jones Amanda 
Published: September 2021

ObjectiveThis study investigated the content, quality and value of feedback given to applicants who applied to one of four research programmes in the UK funded (or jointly funded) by the National Institute for Health Research (NIHR).MethodsA mixed-method phased approach was conducted using document analysis and an online survey. Phase 1 examined 114 NIHR applicant feedback documents comprised written feedback from funding committees and external peer-reviewers and a conceptual framework of the key components of feedback was developed using content analysis. Phase 2 was an online survey completed by 113 NIHR applicants. Frequencies of responses to closed questions were calculated. Perceptions of quality and value of feedback were identified using content analysis of open-text responses.ResultsIn phase 1, a conceptual framework was developed with seven overarching categories: ‘Study structure and quality’; ‘Team and infrastructure’; ‘Acceptability to patients and professionals’; ‘Study justification and design’; ‘Risks and contingencies’; ‘Outputs’; ‘Value for money’. A higher frequency of feedback was provided at stage 2 and for successful applications across the majority of components. In phase 2, frequency data showed that opinion on feedback was dependent on funding outcome. Content analysis revealed four main themes: ‘Committee transparency’; ‘Content validity and reliability’; ‘Additional support’; Recognition of effort and constraints’.ConclusionsThis study provides key insights and understanding into the quality, content and value of feedback provided to NIHR applicants. The study identified key areas for improvement that can arise in NIHR funding applications, as well as in the feedback given to applicants that are applicable to other funding organisations. These findings could be used to inform funding application guidance documents to help researchers strengthen their applications and used more widely by other funders to inform their feedback processes.
Delirium and neuropsychological outcomes in critically Ill patients with COVID-19: a cohort study
Authors: Ragheb Jacqueline , McKinney Amy , Zierau Mackenzie , Brooks Joseph , Hill-Caruthers Maria , Iskander Mina , Ahmed Yusuf , Lobo Remy , Mentz Graciela , Vlisides Phillip E 
Published: September 2021

ObjectiveTo characterise the clinical course of delirium for patients with COVID-19 in the intensive care unit, including postdischarge neuropsychological outcomes.DesignRetrospective chart review and prospective survey study.SettingIntensive care units, large academic tertiary-care centre (USA).ParticipantsPatients (n=148) with COVID-19 admitted to an intensive care unit at Michigan Medicine between 1 March 2020 and 31 May 2020 were eligible for inclusion.Primary and secondary outcome measuresDelirium was the primary outcome, assessed via validated chart review method. Secondary outcomes included measures related to delirium, such as delirium duration, antipsychotic use, length of hospital and intensive care unit stay, inflammatory markers and final disposition. Neuroimaging data were also collected. Finally, a telephone survey was conducted between 1 and 2 months after discharge to determine neuropsychological function via the following tests: Family Confusion Assessment Method, Short Blessed Test, Patient-Reported Outcomes Measurement Information System Cognitive Abilities 4a and Patient-Health Questionnaire-9.ResultsDelirium was identified in 108/148 (73%) patients, with median (IQR) duration lasting 10 (4–17) days. In the delirium cohort, 50% (54/108) of patients were African American and delirious patients were more likely to be female (76/108, 70%) (absolute standardised differences >0.30). Sedation regimens, inflammation, delirium prevention protocol deviations and hypoxic-ischaemic injury were likely contributing factors, and the most common disposition for delirious patients was a skilled care facility (41/108, 38%). Among patients who were delirious during hospitalisation, 4/17 (24%) later screened positive for delirium at home based on caretaker assessment, 5/22 (23%) demonstrated signs of questionable cognitive impairment or cognitive impairment consistent with dementia and 3/25 (12%) screened positive for depression within 2 months after discharge.ConclusionPatients with COVID-19 commonly experience a prolonged course of delirium in the intensive care unit, likely with multiple contributing factors. Furthermore, neuropsychological impairment may persist after discharge.
Comparison of FORTA, PRISCUS and EU(7)-PIM lists on identifying potentially inappropriate medication and its impact on cognitive function in multimorbid elderly German people in primary care: a multicentre observational study
Authors: Krüger Caroline , Schäfer Ingmar , van den Bussche Hendrik , Bickel Horst , Dreischulte Tobias , Fuchs Angela , König Hans-Helmut , Maier Wolfgang , Mergenthal Karola , Riedel-Heller Steffi G , Schön Gerhard , Weyerer Siegfried , Wiese Birgitt , von Renteln-Kruse Wolfgang , Langebrake Claudia , Scherer Martin 
Published: September 2021

ObjectivesOur study aimed to assess the frequency of potentially inappropriate medication (PIM) use (according to three PIM lists) and to examine the association between PIM use and cognitive function among participants in the MultiCare cohort.DesignMultiCare is conducted as a longitudinal, multicentre, observational cohort study.SettingThe MultiCare study is located in eight different study centres in Germany.Participants3189 patients (59.3% female).Primary and secondary outcome measuresThe study had a cross-sectional design using baseline data from the German MultiCare study. Prescribed and over-the-counter drugs were classified using FORTA (Fit fOR The Aged), PRISCUS (Latin for ‘time-honoured’) and EU(7)-PIM lists. A mixed-effect multivariate linear regression was performed to calculate the association between PIM use patients’ cognitive function (measured with (LDST)).ResultsPatients (3189) used 2152 FORTA PIM (mean 0.9±1.03 per patient), 936 PRISCUS PIM (0.3±0.58) and 4311 EU(7)-PIM (1.4±1.29). The most common FORTA PIM was phenprocoumon (13.8%); the most prevalent PRISCUS PIM was amitriptyline (2.8%); the most common EU(7)-PIM was omeprazole (14.0%). The lists rate PIM differently, with an overall overlap of 6.6%. Increasing use of PIM is significantly associated with reduced cognitive function that was detected with a correlation coefficient of −0.60 for FORTA PIM (p=0.002), −0.72 for PRISCUS PIM (p=0.025) and −0.44 for EU(7)-PIM (p=0.005).ConclusionWe identified PIM using FORTA, PRISCUS and EU(7)-PIM lists differently and found that PIM use is associated with cognitive impairment according to LDST, whereby the FORTA list best explained cognitive decline for the German population. These findings are consistent with a negative impact of PIM use on multimorbid elderly patient outcomes.Trial registration numberISRCTN89818205.
Safety and effectiveness of dose-sparing strategies for intramuscular seasonal influenza vaccine: a rapid scoping review
Authors: Lunny Carole , Antony Jesmin , Rios Patricia , Williams Chantal , Ramkissoon Naveeta , Straus Sharon E , Tricco Andrea C 
Published: September 2021

BackgroundThe objective of this rapid scoping review was to identify studies of dose-sparing strategies for administration of intramuscular seasonal influenza vaccines in healthy individuals of all ages.MethodsComprehensive literature searches were executed in MEDLINE, Embase and the Cochrane library. The grey literature was searched via international clinical trial registries for relevant studies published in English in the last 20 years. We included studies in healthy humans of any age that used any dose-sparing strategy to administer intramuscular seasonal influenza vaccines. Title/abstract and full-text screening were carried out by pairs of reviewers independently. Data extraction was conducted by a single reviewer and verified by a second reviewer. Our outcomes were influenza infections, intensive care unit admission, pneumonia, hospitalisations, adverse events and mortality. Results were summarised descriptively.ResultsA total of 13 studies with 10 351 participants were included in the review and all studies were randomised controlled trials (RCTs) conducted between 2006 and 2019. The most common interventions were the trivalent influenza vaccine (n=10), followed by the quadrivalent influenza vaccine (n=4). Nine studies included infants/toddlers 6–36 months old and one of these studies also included children and adolescents. In these nine studies, no clinical effectiveness outcomes were reported. Of the four adult studies (≥18 years), two studies reported on effectiveness outcomes, however, only one RCT reported on laboratory-confirmed influenza.ConclusionsDue to the low number of studies in healthy adults and the lack of studies assessing confirmed influenza and influenza-like illness, there remains a need for further evaluation.
Study protocol for yoga-based lifestyle intervention for healthy ageing phenotype in the older adults (yHAP): a two-armed, waitlist randomised controlled trial with multiple primary outcomes
Authors: Majumdar Vijaya , Snigdha Atmakur , Manjunath N K , Nagarathna Raghuram , Mavathur Ramesh , Singh Amit , S R Kalpana , H R Nagendra 
Published: September 2021

IntroductionThe conceptualisation of healthy ageing phenotype (HAP) and the availability of a tentative panel for HAP biomarkers raise the need to test the efficacy of potential interventions to promote health in older adults. This study protocol reports the methodology for a 24-week programme to explore the holistic influence of the yoga-based intervention on the (bio)markers of HAP.Methods and analysisThe study is a two-armed, randomised waitlist controlled trial with blinded outcome assessors and multiple primary outcomes. We aim to recruit 250 subjects, aged 60–80 years from the residential communities and old age clubs in Bangalore city, India, who will undergo randomisation into intervention or control arms (1:1). The intervention will include a yoga-based programme tailored for the older adults, 1 hour per day for 6 days a week, spread for 24 weeks. Data would be collected at the baseline and post-intervention, the 24th week. The multiple primary outcomes of the study are the (bio)markers of HAP: glycated haemoglobin, low-density lipoprotein cholesterol (LDL-C), systolic blood pressure, and forced expiratory volume in 1 s for physiological and metabolic health; Digit Symbol Substitution Test, Trail Making Tests A and B for cognition; hand grip strength and gait speed for physical capability; loneliness for social well-being and WHO Quality of Life Instrument-Short Form for quality of life. The secondary outcomes include inflammatory markers, tumour necrosis factor-alpha receptor II, C reactive protein, interleukin 6 and serum Klotho levels. Analyses will be by intention-to-treat and the holistic impact of yoga on HAP will be assessed using global statistical test.Ethics and disseminationThe study is approved by the Institutional Ethics Committee of Swami Vivekananda Yoga Anusandhana Samsthana University, Bangalore (ID: RES/IEC-SVYASA/143/2019). Written informed consent will be obtained from each participant prior to inclusion. Results will be available through research articles and conferences.Trial registration numberCTRI/2021/02/031373.
Experiences of trial participants and site staff of participating in and running a large randomised trial within fertility (the endometrial scratch trial): a qualitative interview study
Authors: Chatters Robin , White David , Pye Clare , Petrovic Ana , Sizer Anya , Kumar Pavithra , Metwally Mostafa 
Published: September 2021

ObjectivesTo explore the experiences of endometrial scratch (ES) trial participants and site staff of trial recruitment and participation, in order to improve the experience of participants in future trials.DesignQualitative study of a subset of participants in the ES randomised controlled trial and a subset of trial site staff.SettingA purposeful sample of 9 of the 16 UK Fertility Units that participated in the trial.ParticipantsA purposeful sample of 27 trial participants and 7 site staff.ResultsParticipants were largely happy with the recruitment practices, however, some were overwhelmed with the amount of information received. Interviewees had positive preconceptions regarding the possible effect of the ES on the outcome of their in vitro fertilisation (IVF) cycle, which often originated from their own internet research and seemed to be exacerbated by how site staff described the intervention. Some participants appeared to not understand that receiving the ES could potentially reduce their chances of a successful IVF outcome. Those randomised to the control arm discussed feeling discontent; site staff developed mechanisms of dealing with this.ConclusionsA lack of equipoise in both study participants and the recruiting site staff led to trial participants having positive preconceptions of the potential impact of the ES on their upcoming IVF cycle. Trial participants may not have understood the potential harms of participating in a randomised trial. The trial information sheet did not clearly state this; further research should assess how such information should be presented to potential participants, to proportionately present the level of risk, but to not unduly discourage participation. The amount of information fertility patients require about a research study should also be investigated, in order to avoid participants feeling overwhelmed by the amount of information they receive prior to starting IVF.Trial registration numberISRCTN23800982.
Low lung function, sudden cardiac death and non-fatal coronary events in the general population
Authors: Zaigham Suneela , Eriksson Karl-Fredrik , Wollmer Per , Engström Gunnar 
Published: September 2021

BackgroundMany of those who suffer from a first acute coronary event (CE) die suddenly during the day of the event, most of them die outside hospital. Poor lung function is a strong predictor of future cardiac events; however, it is unknown whether the pattern of lung function impairment differs for the prediction of sudden cardiac death (SCD) versus non-fatal CEs. We examined measures of lung function in relation to future SCD and non-fatal CE in a population-based study.MethodsBaseline spirometry was assessed in 28 584 middle-aged subjects, without previous history of CE, from the Malmö Preventive Project. The cohort was followed prospectively for incidence of SCD (death on the day of a first CE, inside or outside hospital) or non-fatal CE (survived the first day). A modified version of the Lunn McNeil’s competing risk method for Cox regression was used to run models for both SCD and non-fatal CE simultaneously.ResultsA 1-SD reduction in forced expiratory volume in 1 s (FEV1) was more strongly associated with SCD than non-fatal CE even after full adjustment (FEV1: HR for SCD: 1.23 (1.15 to 1.31), HR for non-fatal CE 1.08 (1.04 to 1.13), p value for equal associations=0.002). Similar associations were found for forced vital capacity (FVC) but not FEV1/FVC. The results remained significant even in life-long never smokers (FEV1: HR for SCD: 1.34 (1.15 to 1.55), HR for non-fatal CE: 1.11 (1.02 to 1.21), p value for equal associations=0.038). Similar associations were seen when % predicted values of lung function measures were used.ConclusionsLow FEV1is associated with both SCD and non-fatal CE, but consistently more strongly associated with future SCD. Measurement with spirometry in early life could aid in the risk stratification of future SCD. The results support the use of spirometry for a global assessment of cardiovascular risk.
Palliative care simulation for internal medicine trainees: development and pilot study
Authors: Dewhurst Felicity , Howorth Kate , Billett Hannah , Brown Jolene , Charles Maxwell , Fleming Elizabeth , Gouldthorpe Craig , Huggin Amy , Kavanagh Emily , Kiltie Rachel , Robinson Lucy , Rowley Grace , Simkiss Lauri , Wakefield Donna , Woods Elizabeth , Churm Deepta , Walmsley Rowan , Waterfield Kerry 
Published: September 2021

ObjectivesShape of training has recognised that ‘Managing End-of-Life and Applying Palliative Care Skills’ is a key competency for internal medicine trainees. It provides the opportunity and challenge to improve palliative care training for generalist physicians. Simulation has been recognised internationally as a holistic teaching and assessment method. This study aimed to produce a palliative medicine simulation training package for internal medicine trainees for delivery by palliative medicine trainees providing the former opportunity to practice assessment and management of patients with life-limiting illness and the latter teaching and management opportunities.MethodsA regional group of palliative medicine trainees were trained in simulation and debrief. Nominal and focus group techniques designed a simulation training package. Learning outcomes were mapped to the internal medicine curriculum descriptors.ResultsPalliative simulation for internal medicine trainees (PALL-SIM-IMT) is a training package meeting internal medicine trainees’ curriculum requirements. Regional pilots have demonstrated feasibility for delivery by palliative medicine trainees and improvement in recipients’ confidence in all curriculum descriptors.ConclusionsPALL-SIM-IMT can aid competency achievement for the provision of generalist palliative care by internal medicine trainees. It allows reciprocal development of palliative medicine trainees’ leadership and teaching skills. National adoption and evaluation is ongoing.
PD-1/PD-L1 Inhibitors versus Chemotherapy for Previously Treated Advanced Gastroesophageal Cancer: A Meta-Analysis of Randomized Controlled Trials
Authors: Maoxi Zhong , Jinmin Xue , Xiaozhu Zeng , Yubing Yue , Yuxi Zhu 
Published: September 2021

Patients with advanced gastroesophageal cancer refractory to the previous regimen of chemotherapy suffered from poor prognosis without many effective treatment options. Immune checkpoint inhibitors (ICIs) provide promising efficacy, but the relevant clinical trials have offered controversial data. We performed this meta-analysis to compare the efficacy and safety of inhibitors against programmed cell death receptor 1 (PD-1) and its ligand PD-L1 versus chemotherapy as second or third-line therapy in patients with advanced gastroesophageal cancer. Six randomized controlled trials (RCTs) including 2,648 patients were included. The meta-analysis results indicated that both ORR (RR = 1.39, 95% CI: 0.85∼2.25,

P

= 0.188) and PFS (HR = 1.14, 95% CI: 0.88∼1.46,

P

= 0.316) were not significantly improved by ICIs compared with chemotherapy. However, the OS was significantly prolonged (HR = 0.85, 95% CI: 0.75–0.97,

P

= 0.018) in the ICIs group compared with chemotherapy. Subgroup analysis showed that ICIs provide statistically significant OS benefits over chemotherapy in PD-L1-positive, squamous cell carcinoma, Asia origin, esophageal cancer, second-line treatment, male, and aged 65 or older patients. Compared with chemotherapy, the TRAEs risk of ICIs was reduced by 33% (RR = 0.67, 95% CI: 0.62–0.73,

P

≤ 0.001). And the risk of grades 3–5 of TRAEs was reduced by 60% (RR = 0.40, 95% CI: 0.33–0.49,

P

≤ 0.001). Compared to chemotherapy, ICIs appeared to improve OS and were better tolerated in previously treated patients with advanced esophageal cancer. We recommend PD-1/PD-L1 inhibitors as an optimal treatment option for positive PD-L1 expression, squamous cell carcinoma, Asia origin, esophageal cancer, second-line treatment, male, and ≥65 years of age patients.
Epigenetic Alterations and Mechanisms That Drive Resistance to Targeted Cancer Therapies
Authors: Wajapeyee Narendra , Gupta Romi 
Published: September 2021

Abstract
Cancer is a complex disease and cancer cells typically harbor multiple genetic and epigenetic alterations. Large-scale sequencing of patient-derived cancer samples has identified several druggable driver oncogenes. Many of these oncogenes can be pharmacologically targeted to provide effective therapies for breast cancer, leukemia, lung cancer, melanoma, lymphoma, and other cancer types. Initial responses to these agents can be robust in many cancer types and some patients with cancer experience sustained tumor inhibition. However, resistance to these targeted therapeutics frequently emerges, either from intrinsic or acquired mechanisms, posing a major clinical hurdle for effective treatment. Several resistance mechanisms, both cell autonomous and cell nonautonomous, have been identified in different cancer types. Here we describe how alterations of the transcriptome, transcription factors, DNA, and chromatin regulatory proteins confer resistance to targeted therapeutic agents. We also elaborate on how these studies have identified underlying epigenetic factors that drive drug resistance and oncogenic pathways, with direct implications for the prevention and treatment of drug-resistant cancer.