bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rationale and protocol for the 7- and 8-year longitudinal assessments of eye health in a cohort of young adults in the Raine Study
Authors: Lee Samantha Sze-Yee , Lingham Gareth , Yazar Seyhan , Sanfilippo Paul G , Charng Jason , Chen Fred K , Hewitt Alex W , Ng Fletcher , Hammond Christopher , Straker Leon M , Eastwood Peter R , MacGregor Stuart , Rose Kathryn A , Lucas Robyn M , Guggenheim Jeremy A , Saw Seang-Mei , Coroneo Minas T , He Mingguang , Mackey David A 
Published: March 2020

IntroductionEye diseases and visual impairment more commonly affect elderly adults, thus, the majority of ophthalmic cohort studies have focused on older adults. Cohort studies on the ocular health of younger adults, on the other hand, have been few. The Raine Study is a longitudinal study that has been following a cohort since their birth in 1989–1991. As part of the 20-year follow-up of the Raine Study, participants underwent a comprehensive eye examination. As part of the 27- and 28-year follow-ups, eye assessments are being conducted and the data collected will be compared with those of the 20-year follow-up. This will provide an estimate of population incidence and updated prevalence of ocular conditions such as myopia and keratoconus, as well as longitudinal change in ocular parameters in young Australian adults. Additionally, the data will allow exploration of the environmental, health and genetic factors underlying inter-subject differential long-term ocular changes.Methods and analysisParticipants are being contacted via telephone, email and/or social media and invited to participate in the eye examination. At the 27-year follow-up, participants completed a follow-up eye screening, which assessed visual acuity, autorefraction, ocular biometry and ocular sun exposure. Currently, at the 28-year follow-up, a comprehensive eye examination is being conducted which, in addition to all the eye tests performed at the 27-year follow-up visit, includes tonometry, optical coherence tomography, funduscopy and anterior segment topography, among others. Outcome measures include the incidence of refractive error and pterygium, an updated prevalence of these conditions, and the 8-year change in ocular parameters.Ethics and disseminationThe Raine Study is registered in the Australian New Zealand Clinical Trials Registry. The Gen2 20-year, 27-year and 28-year follow-ups are approved by the Human Research Ethics Committee of the University of Western Australia. Findings resulting from the study will be published in health or medical journals and presented at conferences.Trial registration numberACTRN12617001599369; Active, not recruiting.
Translation and cultural adaptation of a prostate cancer screening decision aid: a qualitative study in Portugal
Authors: Baptista Sofia , Heleno Bruno , Pinto Marta , Guimarães Bruna , China Diogo , Ramos João Pedro , Teixeira Andreia , Taylor Kathryn L , Martins Carlos 
Published: March 2020

ObjectivesTo translate and culturally adapt an English language patient decision aid addressing prostate cancer screening, so it can be used by Portuguese men.DesignQualitative study. We followed the European Centre for Disease Prevention and Control’s (ECDC) five-step, stakeholder-based approach to adapting health communication materials: (1) selection of materials and process coordinators, (2) early review, (3) translation and back translation, (4) comprehension testing with cognitive semi-structured interviews and (5) proofreading. Content analysis was performed using Ligre software.Setting and participantsCognitive interviews with 15 men to refine a decision aid after its translation. Eligible participants were Portuguese native-speaking men aged 55–69 years old recruited from the local community (urban and suburban) of Oporto district through advertisements in social media and senior universities between January and March 2019. A previous diagnosis of prostate cancer was the single exclusion criterion.ResultsFive main themes are presented: informational content, information comprehension, sociocultural appropriateness, feelings and main message and personal perspective concerning prostate cancer screening. Most men found the translated version of the decision aid to be clear, comprehensive and appropriate for its target population, although some suggested that medical terms could be a barrier. The data collected from men’s interviews afforded the researchers the opportunity to clarify concepts and expand existing content.ConclusionsA decision aid was successfully translated and adapted to the Portuguese cultural setting. Our ECDC based approach can be replicated by other workgroups to translate and culturally adapt decision aids.
Hours lying down per day, as a proxy for sedentary behaviour and risk of diabetes in young and middle-aged adults in Norway: an 11-year follow-up of the HUNT study
Authors: Asante Ernest O , Sun Yi-Qian , Nilsen Tom Ivar Lund , Åsvold Bjørn Olav , Sørgjerd Elin Pettersen , Mai Xiao-Mei 
Published: March 2020

ObjectiveWe aimed to examine relationship between hours lying down per day, as a proxy for sedentary behaviour and risk of diabetes in young and middle-aged adults, and to assess if leisure-time physical activity and body mass index (BMI) modified this relationship.DesignA population-based prospective cohort study.SettingNord-Trøndelag, Norway.ParticipantsThe cohort included 17 058 diabetes-free adults, at an age of 20–55 years in 1995–1997, who were followed-up to 2006–2008.Primary outcome measuresIncident diabetes was defined by self-report of diabetes or non-fasting glucose levels greater than 11 mmol/L at the follow-up.MethodsMultivariable logistic regression models were used to obtain OR with 95% CI for risk of diabetes by the categories of hours lying down (≤7, 8 and ≥9 hours/day).Results362 individuals (2.1%) developed diabetes during an average of 11-year follow-up. Individuals who reported lying down ≥9 hours/day had an adjusted OR of 1.35 (95% CI 1.01 to 1.80) for incident diabetes compared with those lying down 8 hours/day. Lying down ≤7 hours/day was not associated with the risk of diabetes. In analysis stratified by physical activity, the ORs associated with lying down ≥9 hours/day were 1.41 (95% CI 1.05 to 1.90) and 0.90 (95% CI 0.23 to 3.55), respectively, among the less active and highly active individuals (pinteraction=0.048). There was little evidence that the association differed by BMI status (pinteraction=0.62).ConclusionsProlonged hours lying down per day was associated with an increased risk of diabetes in young and middle-aged adults. The positive association appeared to be modified by physical activity but not by BMI.
Enzyme replacement in advanced pancreatic cancer: patient perceptions
Authors: Landers Amanda , McKenzie Clare , Pitama Suzanne G , Brown Helen 
Published: March 2020

PurposeAdvanced pancreatic cancer has a universally poor survival rate. Patients frequently develop malabsorption that requires pancreatic enzyme replacement therapy (PERT). This study explores the experience of patient engagement with PERT and how the medication is taken and tolerated.MethodsParticipants with advanced pancreatic cancer requiring PERT were interviewed after referral to a specialist palliative care team. An inductive analysis was used to code the data. Theoretical sufficiency was reached after 12 participants.ResultsFour themes emerged from the interviews-patient context, health literacy, relationship to food and experience of taking the pancreatic enzymes. Respondents brought their own life experiences into the clinical encounter when told of the diagnosis. Patients had high levels of understanding and engagement with the diagnosis and treatment, understood the benefits of PERT in digestion and tolerated the medication well.ConclusionsPatients with metastatic pancreatic cancer understand the life-limiting nature of their illness. They want to participate in their healthcare decisions and are capable of complex medication titration when given good explanations and they experience benefits. PERT should be offered to these patients by a team of knowledgeable health professionals with good communication skills that can continue to support and review their needs.
Specialist palliative medicine physicians and nurses accuracy at predicting imminent death (within 72 hours): a short report
Authors: White Nicola , Reid Fiona , Vickerstaff Victoria , Harries Priscilla , Stone Patrick 
Published: March 2020

ObjectivesResearch suggests that clinicians are not very accurate at prognosticating in palliative care. The ‘horizon effect’ suggests that accuracy ought to be better when the survival of patients is shorter. The aim of this study was to determine the accuracy of specialist palliative care clinicians at identifying which patients are likely to die within 72 hours.DesignIn a secondary data analysis of a prospective observational study, specialist palliative care doctors and nurses (in a hospice and a hospital palliative care team) provided survival predictions (yes/no/uncertain) about which patients would die within 72 hours.ResultsSurvival predictions were obtained for 49 patients. A prediction from a nurse was obtained for 37/49 patients. A prediction from a doctor was obtained for 46/49 patients. In total, 23 (47%)/49 patients actually died within 72 hours of assessment. Nurses accurately predicted the outcome in 27 (73%)/37 cases. Doctors accurately predicted the outcome in 30 (65%)/46 cases. When comparing predictions given on the same patients (27 [55%]/49), nurses were slightly better at recognising imminent death than doctors (positive predictive value (the proportion of patients who died when the clinician predicted death)=79% vs 60%, respectively). The difference in c-statistics (nurses 0.82 vs doctors 0.63) was not significant (p=0.13).ConclusionEven when patients are in the terminal phase and close to death, clinicians are not very good at predicting how much longer they will survive. Further research is warranted to improve prognostication in this population.
Electrocardiographic associations with myocardial fibrosis among sudden cardiac death victims
Authors: Holmström Lauri , Haukilahti Anette , Vähätalo Juha , Kenttä Tuomas , Appel Henrik , Kiviniemi Antti , Pakanen Lasse , Huikuri Heikki V , Myerburg Robert J , Junttila Juhani 
Published: March 2020

ObjectiveA major challenge in reducing the incidence of sudden cardiac death (SCD) is the identification of patients at risk. Myocardial fibrosis has a substantial association with SCD risk but is difficult to identify among general populations. Our aim was to find electrocardiographic (ECG) markers of myocardial fibrosis among SCD victims.MethodsStudy population was acquired from the Fingesture study, which has gathered data from 5869 consecutive autopsied SCD victims in Northern Finland between 1998 and 2017. The degree of fibrosis was determined in histological samples taken from the heart during autopsy and was categorised into four groups: (1) no fibrosis, (2) scattered mild fibrosis, (3) moderate patchy fibrosis and (4) substantial fibrosis. We were able to collect ECGs from 1100 SCD victims.ResultsThe mean age of the study subjects was 66±13 years and 75% were male. QRS duration in ECG correlated with the degree of fibrosis (p<0.001, β=0.153). Prevalence of fragmented QRS complex, pathological Q waves and T wave inversions correlated with increased degree of fibrosis (p<0.001 in each). Depolarisation abnormalities were observed both in ischaemic and non-ischaemic heart disease. Repolarisation abnormalities reached statistical significance only among ischaemic SCD victims. An abnormal ECG was observed in 75.3% of the subjects in group 1, 73.7% in group 2, 88.5% in group 3 and 91.7% in group 4 patients (p<0.001).ConclusionsMyocardial fibrosis was associated with QRS prolongation, deep Q waves, T wave inversions and QRS fragmentation. The results provide potentially useful non-invasive early recognition of patients with fibrotic cardiomyopathy and risk of SCD.
Clinicopathologic characterisation of myeloid neoplasms with concurrent spliceosome mutations and myeloproliferative-neoplasm-associated mutations
Authors: Liu Yen-Chun , Illar Gwendolyn M , Bailey Nathanael Glen 
Published: March 2020

AimsSpliceosome genes (SF3B1,SRSF2,U2AF1andZRSR2) are commonly mutated in myeloid neoplasms, particularly in myelodysplastic syndromes (MDS).JAK2,MPLandCALRmutations are associated with myeloproliferative neoplasms (MPN). AlthoughSF3B1and MPN-associated mutations frequently co-occur in the rare entity MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), myeloid neoplasms with concurrent spliceosome and MPN-associated mutations encompass many disease entities and are not well characterised.MethodsSpecimens from 2016 to 2019 with concurrent spliceosome and MPN-associated mutations were identified, and the clinicopathologic features were assessed.ResultsThe 36 cases were divided into mutational categories based on their spliceosome mutation. At diagnosis, cases with concurrentU2AF1and MPN-associated mutations had lower leucocyte counts and platelet counts than did the other groups. Cases with mutantSRSF2were more likely to haveASXL1andIDH2mutations, whileU2AF1-mutated neoplasms were more likely to have an abnormal karyotype. The most commonSF3B1K700 andU2AF1S34 mutational hotspots were underrepresented in our cohort of myeloid neoplasms with concurrent spliceosome and MPN-associated mutations, asSF3B1andU2AF1mutations tended to involve other codons. Numerous WHO-defined disease entities were represented in each spliceosome gene category; although MDS/MPN-RS-T were only identified in the group withSF3B1mutations, they constituted only 1/4 of the neoplasms in the category.ConclusionsMyeloid neoplasms with different mutant splicing factor and concurrent MPN-associated mutations demonstrate somewhat different clinical and pathologic features, but t he association between genotypes and phenotypes in these overlapping neoplasms is not straightforward.
Performance of anti-CD19 chimeric antigen receptor T cells in genetically defined classes of chronic lymphocytic leukemia
Authors: Mancikova Veronika , Peschelova Helena , Kozlova Veronika , Ledererova Aneta , Ladungova Adriana , Verner Jan , Loja Tomas , Folber Frantisek , Mayer Jiri , Pospisilova Sarka , Smida Michal 
Published: March 2020

BackgroundWhile achieving prolonged remissions in other B cell-derived malignancies, chimeric antigen receptor (CAR) T cells still underperform when injected into patients with chronic lymphocytic leukemia (CLL). We studied the influence of genetics on CLL response to anti-CD19 CAR T-cell therapy.MethodsFirst, we studied 32 primary CLL samples composed of 26 immunoglobulin heavy-chain gene variable (IGHV)-unmutated (9ATM-mutated, 8TP53-mutated, and 9 without mutations inATM,TP53,NOTCH1orSF3B1) and 6IGHV-mutated samples without mutations in the above-mentioned genes. Then, we mimicked the leukemic microenvironment in the primary cells by ‘2S stimulation’ through interleukin-2 and nuclear factor kappa B. Finally, CRISPR/Cas9-generatedATM-knockout andTP53-knockout clones (four and seven, respectively) from CLL-derived cell lines MEC1 and HG3 were used. All these samples were exposed to CAR T cells. In vivo survival study in NSG mice using HG3 wild-type (WT),ATM-knockout orTP53-knockout cells was also performed.ResultsPrimary unstimulated CLL cells were specifically eliminated after >24 hours of coculture with CAR T cells. ‘2S’ stimulated cells showed increased survival when exposed to CAR T cells compared with unstimulated ones, confirming the positive effect of this stimulation on CLL cells’ in vitro fitness. After 96 hours of coculture, there was no difference in survival among the genetic classes. Finally, CAR T cells were specifically activated in vitro in the presence of target knockout cell lines as shown by the production of interferon-γ when compared with control (CTRL) T cells (p=0.0020), but there was no difference in knockout cells’ survival. In vivo, CAR T cells prolonged the survival of mice injected with WT,TP53-knockout andATM-knockout HG3 tumor cells as compared with CTRL T cells (p=0.0485, 0.0204 and <0.0001, respectively). When compared withATM-knockout,TP53-knockout disease was associated with an earlier time of onset (p<0.0001), higher tumor burden (p=0.0002) and inefficient T-cell engraftment (p=0.0012).ConclusionsWhile in vitro no differences in survival of CLL cells of various genetic backgrounds were observed, CAR T cells showed a different effectiveness at eradicating tumor cells in vivo depending on the driver mutation. Early disease onset, high-tumor burden and inefficient T-cell engraftment, associated withTP53-knockout tumors in our experimental setting, ultimately led to inferior performance of CAR T cells.
Clinical prognosis of FLAIR hyperintense arteries in ischaemic stroke patients: a systematic review and meta-analysis
Authors: Zhou Zien , Malavera Alejandra , Yoshimura Sohei , Delcourt Candice , Mair Grant , Al-Shahi Salman Rustam , Demchuk Andrew M , Wardlaw Joanna M , Lindley Richard I , Anderson Craig S 
Published: March 2020

ObjectiveWe performed a systematic review and meta-analysis to determine the association of fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) on brain MRI and prognosis after acute ischaemic stroke (AIS).MethodsWe searched Medline, Embase and Cochrane Central Register of Controlled Trials for studies reporting clinical or imaging outcomes with presence of FLAIR-HAs after AIS. Two researchers independently assessed eligibility of retrieved studies and extracted data, including from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Outcomes were unfavourable functional outcome (primary, modified Rankin scale scores 3–6 or 2–6), death, intermediate clinical and imaging outcomes. We performed subgroup analyses by treatment or types of FLAIR-HAs defined by location (at proximal/distal middle cerebral artery (MCA), within/beyond diffusion-weighted imaging (DWI) lesion) or extent.ResultsWe included 36 cohort studies (33 prospectively collected) involving 3577 patients. FLAIR-HAs were not associated with functional outcome overall (pooled risk ratio 0.87, 95% CI 0.71 to 1.06), but were significantly associated with better outcome in those receiving endovascular therapy (0.56, 95% CI 0.41 to 0.75). Contrary to FLAIR-HAs at proximal MCA or within DWI lesions, FLAIR-HAs beyond DWI lesions were associated with better outcome (0.67, 95% CI 0.57 to 0.79). FLAIR-HAs favoured recanalisation (1.21, 95% CI 1.06 to 1.38) with increased risk of intracerebral haemorrhage (2.07, 95% CI 1.37 to 3.13) and early neurological deterioration (1.93, 95% CI 1.30 to 2.85).ConclusionsFLAIR-HAs were not associated with functional outcome overall but were associated with outcome after endovascular therapy for AIS. FLAIR-HAs were also associated with early recanalisation or haemorrhagic complications, and early neurologic deterioration.PROSPERO registration numberCRD42019131168.
Real-world treatment patterns, healthcare resource utilisation and costs in patients with systemic lupus erythematosus treated with belimumab: a retrospective analysis of claims data in the USA
Authors: Bell Christopher F , Priest Julie , Stott-Miller Marni , Kan Hong , Amelio Justyna , Song Xue , Limone Brendan , Noxon Virginia , Costenbader Karen H 
Published: March 2020

ObjectiveTo examine the effects of belimumab initiation on healthcare resource utilisation (HCRU) and costs in SLE.MethodsThis retrospective observational cohort study used healthcare administrative claims data from the IBM MarketScan Commercial Claims and Encounters Database to identify patients with SLE billing codes who received ≥1 intravenous belimumab infusion between March 2011 and December 2015. The first belimumab administration was the ‘index date’. During the 6-month postindex period, nine belimumab infusions were recommended: three during the initiation period and six during the maintenance period. HCRU and cost data for inpatient admissions, emergency department visits, physician office visits, hospital-based outpatient visits, laboratory services, other outpatient services and outpatient pharmacy prescriptions were compared in the 6-month pre/postindex periods.ResultsOf the 1879 patients with SLE included, 43% received ≥3 intravenous initiation administrations. An average of 5.3 (SD: 2.4) of the nine recommended belimumab administrations were received within 6 months. In the 6-month preindex versus postindex periods, significant reductions were noted for inpatient hospitalisations (18% vs 9%, p<0.001; mean visits: 0.3 vs 0.14, p<0.001) and emergency department visits (40% vs 24%, p<0.001; mean visits; 3.53 vs 1.96, p<0.001). Mean total costs were higher in the 6-month postindex versus preindex period ($41 426 vs $29 270; p<0.001).ConclusionsIn this study of real-world intravenous belimumab for SLE, adherence to recommended infusion schedules was low. Outpatient healthcare and associated costs were higher in the 6 months after belimumab was initiated, although inpatient costs were lower. Reasons for non-adherence with belimumab and implications should be investigated.
Who maintains good health functioning? The contribution of social, work-related and behavioural factors to mental and physical health functioning trajectories in ageing employees
Authors: Lallukka Tea , Hiilamo Aapo , Pietiläinen Olli , Mänty Minna , Kouvonen Anne , Rahkonen Ossi 
Published: March 2020

ObjectivesThe determinants of poor functioning and subsequent early exit from work are well established but very little is known about the positive determinants of maintaining good functioning among the ageing workforce. We investigated modifiable determinants of maintaining good mental and physical health functioning.MethodsWe used prospective survey data collected across four waves among the midlife employees of the City of Helsinki, Finland, 2000–2017 (n=3342). Health functioning was repeatedly measured using the Short Form 36 (SF-36) inventory. Trajectories of mental and physical health functioning were separately examined using group-based trajectory analysis. Multinomial logistic regression models were fitted to examine determinants of each trajectory.ResultsFour trajectory solutions for the developmental patterns in health functioning during the follow-up period were selected, with a slightly different shape of the first trajectory for mental and physical functioning: (1) continuously low (mental), low and decreasing (physical), (2) increasing, (3) decreasing and (4) continuously high functioning. After adjustments, the employees in the continuously high mental health functioning group were more likely to have optimal job demands, high job control, no sleep problems and no binge drinking behaviour. Employees in the continuously high physical functioning group had more likely low levels of physically strenuous work and hazardous working environment and no sleep problems and normal weight.ConclusionHigh job control, good sleep and avoiding binge drinking may help maintain good mental health functioning. Low levels of physical or environmental work exposures, good sleep and recommended healthy weight may support maintenance of good physical health functioning among ageing employees.