bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Eravacycline Versus Best Previously Available Therapy for Adults With Pneumonia Due to Difficult-to-Treat Resistant (DTR) Acinetobacter baumannii
Authors: Scott Courtney J. , Zhu Elizabeth , Jayakumar Rebecca A. , Shan Guogen , Viswesh Velliyur 
Published: May 2022

Background Multidrug-resistant Acinetobacter baumannii remains challenging to treat. Although eravacycline has in vitro activity against this pathogen, there are no studies evaluating outcomes. Objective To assess the efficacy of eravacycline compared with best previously available therapy in adults with difficult-to-treat resistant (DTR) A. baumannii pneumonia. Methods This was a retrospective study of adults hospitalized for pneumonia with DTR A. baumannii. Patients receiving eravacycline were compared with those receiving best previously available therapy. The primary outcome was 30-day in-hospital mortality. Secondary outcomes included clinical cure at Day 14, hospital and intensive care unit (ICU) length of stay, microbiologic cure, and readmission within 90 days with a positive A. baumannii respiratory culture. Results Ninety-three patients were included, with 27 receiving eravacycline. Eravacycline was associated with higher 30-day mortality (33% vs 15%; P = 0.048), lower microbiologic cure (17% vs 59%; P = 0.004), and longer durations of mechanical ventilation (10.5 vs 6.5 days; P = 0.016). At baseline, eravacycline patients had more A. baumannii bacteremia and coinfection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Among bacteremic patients, all 4 receiving eravacycline died by Day 30 and both patients receiving best previously available therapy survived. Upon exclusion of patients with bacteremia and SARS-CoV-2, there were no differences between the groups across any outcomes. Conclusions Eravacycline-based combination therapy had similar outcomes to best previously available combination therapy for adults with DTR A. baumannii pneumonia. However, eravacycline should be used with caution in the setting of bacteremia as outcomes were poor in this population.
Causes of Sudden Unexpected Death in Childhood: Autopsy Findings from a Specialist Centre
Authors: Bryant Victoria A , Jacques Tom S , Sebire Neil J 
Published: May 2022

Objectives: To investigate the aetiologies of sudden unexpected death from natural causes in children aged 1-18 years by retrospective examination of autopsy records from a single centre. Materials and methods: The post-mortem findings from 548 children (1996-2015) were examined. Details were entered into an established research database and categorized according to >400 pre-defined criteria. Results: There were 265 previously apparently healthy children and 283 with pre-existing, potentially life-limiting, conditions. There were more males than females (M:F 1.4:1), and deaths were more frequent in the winter. Infection was commonest accounting for 43% of all deaths. Non-infectious diseases were identified as cause of death in 28%, and 29% of all deaths were unexplained. There was no significant difference in the proportions of deaths in each category between the previously healthy children and those with pre-existing conditions. Conclusion: Sudden unexpected death is a rare presentation of death in childhood and those with pre-existing conditions may be more at risk. Standardisation of the post-mortem procedure in such cases may result in more ancillary investigations performed as routine and may reduce the number of cases that are ‘unexplained’.
The seventh survey of the Tromsø Study (Tromsø7) 2015–2016: study design, data collection, attendance, and prevalence of risk factors and disease in a multipurpose population-based health survey
Authors: Hopstock Laila A. , Grimsgaard Sameline , Johansen Heidi , Kanstad Kristin , Wilsgaard Tom , Eggen Anne Elise 
Published: May 2022

Aims: The Tromsø Study is an ongoing population-based health study in Tromsø, Norway, initiated in 1974. The purpose of the seventh survey (Tromsø7) 2015–2016 was to advance the population risk factor surveillance and to collect new types of data. We present the study design, data collection, attendance, and prevalence of risk factors and disease. Methods: All inhabitants in Tromsø municipality, Norway, aged 40 years and older ( N=32,591) were invited to a health screening including extensive questionnaires, face-to-face interviews, biological sampling (blood, urine, saliva, nasal/throat swabs, faeces), measurements (anthropometry, blood pressure, pulse, pulse oximetry) and clinical examinations (pain sensitivity, echocardiography, cognitive, physical, and lung function, accelerometer measurements, eye examinations, carotid ultrasound, electrocardiography, dual-energy X-ray absorptiometry, and heart, lung and carotid auscultation). New research areas in this round were dental and oral health examinations, collection of faecal samples for studies of normal bacterial flora and antibiotic resistance, and 24-hour urine samples for examination of sodium and iodine intakes. Results: Attendance was 65% ( N=21,083), and was higher in women, age group 50–79 years, previous attenders, and Norwegian-born individuals. Cardiovascular risk factor levels and prevalence of chronic obstructive lung disease decreased since the last survey, while the prevalence of obesity and diabetes increased. Conclusions: Attendance was stable from the sixth survey. Interaction with participants might be key to maintain participation. Favourable trends in risk factors continue, except for a continued increase in obesity. Both new data collection technology and traditional physical examinations will be crucial for the impact of future population studies.
Risk-proportionate approach to paediatric clinical trials: The legal requirements, challenges, and the way forward under the European Union Clinical Trials Regulation
Authors: Wan Mandy , Alessandrini Elisa , Brogan Paul , Eleftheriou Despina , Warris Adilia , Brüggemann Roger , Turner Mark 
Published: May 2022

Background It is now widely accepted that there is a need for safety and efficacy data on medicines used in children. In the European Union, legislation has provided the necessary framework obligating and incentivizing pharmaceutical companies to carry out appropriate paediatric research to support the development of new medicines. This change in research culture, that medicines used in children should be appropriately researched in children, has also led to the recognition of the importance of investigator-initiated clinical trials in furthering medical knowledge on the off-label use of authorized medicines for which paediatric data are often limited. However, medicines regulatory authorities of European Union countries have largely adopted a uniform approach to the regulation of both industry-sponsored and investigator-initiated trials and, in doing so, have added disproportionate burden to the conduct of paediatric clinical trials investigating authorized medicines. Case studies Two European multinational paediatric clinical trials funded by the conect4children consortium are presented to provide a comparative insight into past challenges and to illustrate how the new framework provided by the European Clinical Trials Regulation (No. 536/2014) addresses these barriers in practice. Conclusion The European Clinical Trials Regulation gives a strong impetus to a risk-proportionate approach and offers a path for more efficient delivery of investigator-initiated paediatric clinical trials.
Quality of life of patients with soft tissue sarcoma treated with doxorubicin in the ANNOUNCE phase III clinical trial
Authors: Van Tine Brian A , Krarup-Hansen Anders , Hess Lisa M , Abdul Razak Albiruni R , Soldatenkova Victoria , Wright Jennifer , Park Se Hoon 
Published: May 2022

Background: Patient-reported outcomes (PROs), including health-related quality of life, are recommended to be routinely collected in clinical trials, but data are limited from trials of sarcoma patients. In this analysis, pooled PRO data are reported from patients with advanced or metastatic soft tissue sarcoma (STS) enrolled to the ANNOUNCE phase III trial of doxorubicin-based therapy. Methods: ANNOUNCE was a phase III trial that randomized 509 patients with STS to receive up to eight cycles of doxorubicin with olaratumab or placebo, followed by single-agent olaratumab or placebo. Dexrazoxane was allowed at any cycle of treatment. Participants completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30, which is scored 0–100), and Brief Pain Inventory Short Form Modified (mBPI-sf, scored from 0–10) at each treatment cycle. A descriptive analysis of the longitudinal data was conducted overall and by cumulative dose of doxorubicin received to inform the clinical care of patients with STS. Worsening on the QLQ-C30 was defined as a change of 10 points or more at any post-baseline assessment. Worsening on the mPBI-sf was defined as an increase of ≥2 points from baseline. Results: The majority of participants completed the baseline and at least one subsequent PRO assessment within the trial ( n = 460, 90.4% EORTC QLQ-C30; n = 454, 89.2%, mBPI-sf). Patients with STS enrolled to the ANNOUNCE trial had clinically meaningful problems with physical function and pain before initiating doxorubicin. Overall, those with fewer symptoms or better function at baseline received higher cumulative doxorubicin dose throughout the study. At baseline, mean QLQ-C30 fatigue was 29.9 with a median time to first worsening of 0.9 months, and mean nausea/vomiting was 6.5 with 1.4 months until worsening; mean physical function was 78.3 with median time to worsening of 2.1 months and mean health status was 66.8 with median time to first worsening of 1.6 months. Median time to worsening of pain was 7.9 months. Conclusion: Patients with advanced or metastatic sarcoma reported a relatively rapid decline in PROs during doxorubicin-based treatment, with patients with poorer symptoms at baseline (specifically fatigue), subsequently receiving less doxorubicin therapy. The availability of detailed summary data from the patient perspective during doxorubicin-based treatment may inform future care of these patients and can provide a resource for the development of PRO endpoints in future trials.
Granulomatosis With Polyangiitis Presenting as Occlusive Retinal Vasculitis
Authors: D’Aquila Madeline L. , John Vishak J. 
Published: May 2022

Purpose: We discuss an unusual case of granulomatosis with polyangiitis (GPA) presenting as anterior uveitis with occlusive retinal vasculitis. Methods: A case report is presented. Results: A 60-year-old woman with a history of autoimmune disease presented to the retina clinic with red eyes and blurry vision in both eyes. An examination showed anterior uveitis with retinal vasculitis, and topical steroids were started in both eyes. One month later, the patient’s vision worsened and an optical coherence tomography scan showed new central cystoid macular edema in the left eye. An antivascular endothelial growth factor injection was given. The next day, her vision was “black” in the left eye and a fundus examination showed global ischemia. A comprehensive uveitis workup was positive for cytoplasmic-staining antineutrophilic cytoplasmic antibody. A diagnosis of GPA was confirmed with a renal biopsy. Conclusions: Physician awareness of ocular GPA presentation is vital, and GPA management is most successful with a multidisciplinary team.
Caregiver-specific factors and orphanage-context factors contributing to maltreatment of children in institutional care: A multi-level analysis of 24 orphanages in Tanzania
Authors: Mkinga Getrude , Kirika Anette , Nkuba Mabula , Mgode Simeon , Huth Mira , Hecker Tobias 
Published: May 2022

Background: High rates of maltreatment and low caregiving quality in institutional care settings have been identified in various low-and middle-income countries. Many studies have focused on children living in institutions. Objective: This study investigates the prevalence of maltreatment, caregiver-specific, orphanage-context factors, and their relation to maltreatment of orphans from the caregivers’ perspective. Participants and setting: In this cross-sectional study, 227 caregivers (67% female) with a mean age of 36.84 years ( SD age = 12.89) of 24 childcare centres in Dar es Salaam, Tanzania participated. Methods: The primary outcome was the maltreatment of children assessed through structured interviews of caregivers. Further information on individual (like work-related stress) and structural variables (working conditions) was gathered. Results: Caregivers’ work under extreme and exhausting conditions, with very high caregiver-child ratios, low salaries, and almost no possibility to recover. Results also showed significant differences in the maltreatment level and structural and individual factors (e.g., payment and days of entitlement) between the orphanages. Caregiver’s positive attitudes towards violence ( ƒ2attitudes = 0.19) and difficulties in the relationship with children ( ƒ2relationship = 0.05) significantly predicted maltreatment with moderate and small effects. Conclusions: The overall poor working conditions highlight the urgent need to reduce the caregivers’ burden. In addition to this, addressing caregivers’ positive attitudes and improving their interaction competencies with children may be a starting point to prevent maltreatment of children. Further investigation of structural factors contributing to maltreatment is essential to develop recommendations for the improvement and re-organization of childcare institutions.
The Atrophy of the Vagus Nerve Correlated With Gastrointestinal Non-Motor Symptoms Scores, in Parkinson’s Disease: A Sonography Research Study
Authors: Özçağlayan Ömer , Altunan Bengü , Kurtoğlu Özçağlayan Tuğba İlkem , Ünal Aysun 
Published: May 2022

Objective: To investigate the vagus nerve (VN) dimensional changes with Parkinson’s disease (PD), compared with healthy subjects. Additionally, it is important to investigate whether there is any relationships between these changes and patient’s motor and non-motor symptoms (NMS) of PD. Materials and Methods: A cohort of 43 patients with PD formed a group that was compared with 44 patients without PD, denoted as the healthy subject (HS) group. The diameter and areas of VN of study groups were measured using ultrasonography (US). The study groups were further divided into <65 and ≥65 subgroups, to evaluate the possible effect of age on the VN and evaluated relationships of VN dimensions, between subgroups. In the PD group, a correlational analysis was conducted between the diameter and area of the VN and the motor and NMS scores. Results: There was statistically significant difference in right ( P = .002) and left VN diameters ( P = .007) and in right ( P = .001) and left VN areas ( P = .007), between study groups. There was no significant difference in right and left VN diameters and the right and left VN areas, between subgroups. There was moderately negative correlation between gastrointestinal NMS scores and right VN area ( r = −0.499, P = .002), left VN area ( r = −0.499, P = .002), right VN diameter ( r = −0.378, P = .023), left VN diameter ( r = −0.385, P = .021), respectively. Conclusion: The US demonstrated that VN dimensions may possibly reduce in those patients affected by PD. In this cohort, it appears that an increase in gastrointestinal NMS scores may be explained by atrophy of the VN.
Lenalidomide promotes the development of TP53-mutated therapy-related myeloid neoplasms
Authors: Sperling Adam S. , Guerra Veronica A. , Kennedy James A. , Yan Yuanqing , Hsu Joanne I. , Wang Feng , Nguyen Andrew T. , Miller Peter G. , McConkey Marie E. , Quevedo Barrios Vanessa A. , Furudate Ken , Zhang Linda , Kanagal-Shamanna Rashmi , Zhang Jianhua , Little Latasha , Gumbs Curtis , Daver Naval , DiNardo Courtney D. , Kadia Tapan , Ravandi Farhad , Kantarjian Hagop , Garcia-Manero Guillermo , Futreal P. Andrew , Ebert Benjamin L. , Takahashi Koichi 
Published: May 2022

Abstract
There is a growing body of evidence that therapy-related myeloid neoplasms (t-MNs) with driver gene mutations arise in the background of clonal hematopoiesis (CH) under the positive selective pressure of chemo- and radiation therapies. Uncovering the exposure relationships that provide selective advantage to specific CH mutations is critical to understanding the pathogenesis and etiology of t-MNs. In a systematic analysis of 416 patients with t-MN and detailed prior exposure history, we found that TP53 mutations were significantly associated with prior treatment with thalidomide analogs, specifically lenalidomide. We demonstrated experimentally that lenalidomide treatment provides a selective advantage to Trp53-mutant hematopoietic stem and progenitor cells (HSPCs) in vitro and in vivo, the effect of which was specific to Trp53-mutant HSPCs and was not observed in HSPCs with other CH mutations. Because of the differences in CK1α degradation, pomalidomide treatment did not provide an equivalent level of selective advantage to Trp53-mutant HSPCs, providing a biological rationale for its use in patients at high risk for t-MN. These findings highlight the role of lenalidomide treatment in promoting TP53-mutated t-MNs and offer a potential alternative strategy to mitigate the risk of t-MN development.
People living with moderate-to-severe COPD prefer improvement of daily symptoms over the improvement of exacerbations: a multicountry patient preference study
Authors: Cook Nigel S. , Criner Gerard J. , Burgel Pierre-Régis , Mycock Katie , Gardner Tom , Mellor Phil , Hallworth Pam , Sully Kate , Tatlock Sophi , Klein Beyza , Jones Byron , Le Rouzic Olivier , Adams Kip , Phillips Kirsten , McKevitt Mike , Toyama Kazuko , Gutzwiller Florian S. 
Published: May 2022

IntroductionThis patient preference study sought to quantify the preferences of people living with COPD regarding symptom improvement in the UK, USA, France, Australia and Japan.MethodsThe inclusion criteria were people living with COPD aged 40 years or older who experienced ≥1 exacerbation in the previous year with daily symptoms of cough and excess mucus production. The study design included: 1) development of an attributes and levels grid through qualitative patient interviews; and 2) implementation of the main online quantitative survey, which included a discrete choice experiment (DCE) to allow assessment of attributes and levels using hypothetical health state profiles. Preference weights (utilities) were derived from the DCE using hierarchical Bayesian analysis. A preference simulator was developed that enabled different health state scenarios to be evaluated based on the predicted patient preferences.Results1050 people living with moderate-to-severe COPD completed the survey. All attributes were considered important when patients determined their preferences in the DCE. In a health state preference simulation, two hypothetical health states (comprising attribute levels) with qualitatively equivalent improvements in A) cough and mucus and B) shortness of breath (SOB) resulted in a clear preference for cough and mucus improved profile. When comparing two profiles with C) daily symptoms improved and D) exacerbations improved, there was a clear preference for the daily symptoms improved profile.ConclusionsPeople living with moderate-to-severe COPD prefer to reduce cough and mucus production together over improvement of SOB and would prefer to reduce combined daily symptoms over an improvement in exacerbations.
Identification of immune infiltration-related genes as prognostic indicators for hepatocellular carcinoma
Authors: Dai Kunfu , Liu Chao , Guan Ge , Cai Jinzhen , Wu Liqun 
Published: May 2022

AbstractHepatocellular carcinoma (HCC) has a high degree of malignancy and a poor prognosis. Immune infiltration-related genes have shown good predictive value in the prognosis of many solid tumours. In this study, we established and verified prognostic biomarkers consisting of immune infiltration-related genes in HCC. Gene expression data and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. Differential gene expression analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression algorithm were used to screen prognostic immune infiltration-related genes and to construct a risk scoring model. Kaplan-Meier (KM) survival plots and receiver operating characteristic (ROC) curve analysis were used to evaluate the prognostic performance of the risk scoring model in the TCGA-HCC cohort. In addition, a nomogram model with a risk score was established, and its predictive performance was verified by ROC analysis and calibration plot analysis in the TCGA-HCC cohort. Gene set enrichment analysis (GSEA) identified pathways and biological processes that may be enriched in the high-risk group. Finally, immune infiltration analysis was used to explore the characteristics of the tumour microenvironment related to the risk score. We identified 17 immune infiltration-related genes with prognostic value and constructed a risk scoring model. ROC analysis showed that the risk scoring model can accurately predict the 1-year, 3-year, and 5-year overall survival (OS) of HCC patients in the TCGA-HCC cohort. KM analysis showed that the OS of the high-risk group was significantly lower than that of the low-risk group (P < 0.001). The nomogram model effectively predicted the OS of HCC patients in the TCGA-HCC cohort. GSEA indicated that the immune infiltration-related genes may be involved in biological processes such as amino acid and lipid metabolism, matrisome and small molecule transportation, immune system regulation, and hepatitis virus infection. Immune infiltration analysis showed that the level of immune cell infiltration in the high-risk group was low, and the risk score was negatively correlated with infiltrating immune cells. Our prognostic model based on immune infiltration-related genes in HCC could help the prognostic assessment of HCC patients and provide potential targets for HCC inhibition.