bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rebubbling and graft failure in Descemet membrane endothelial keratoplasty: a prospective Dutch registry study
Authors: Dunker Suryan , Winkens Bjorn , van den Biggelaar Frank , Nuijts Rudy , Kruit Pieter Jan , Dickman Mor 
Published: February 2021

AimsTo identify risk factors for rebubbling, and early graft failure after Descemet membrane endothelial keratoplasty (DMEK).MethodsIn this prospective registry study, all consecutive DMEK procedures registered in the Netherlands Organ Transplant Registry were assessed (n=752). Univariable and multivariable analysis was performed using logistic regression. The effect of rebubbling on endothelial cell density was analysed using a linear mixed model.Results144 of 752 (19%) eyes underwent rebubbling. Rebubbling was successful in 101 eyes (70%). In eyes that underwent rebubbling, the graft failure rate was significantly higher than eyes that did not undergo rebubbling (30% vs 9%, respectively; OR: 4.28, 95% CI 2.72 to 6.73, p<0.001). In multivariable analysis, independent risk factors for rebubbling were surgical complication (OR: 2.28, 95% CI 1.20 to 4.33, p=0.012) and older recipient age (OR: 1.04 (per increase of 1 year), 95% CI 1.01 to 1.07, p=0.003). Risk factors for developing graft failure within 3 months were transplant before 2016 (OR: 3.32, 95% CI 1.87 to 5.90, p<0.001), and surgical complication (OR: 2.93, 95% CI 1.42 to 6.04, p=0.004). Throughout the study period, rebubbling and early graft failure were inversely related. Eyes that underwent rebubbling showed significantly lower endothelial cell densities at 3, 6 and 12 months compared with eyes that did not undergo rebubbling (all p<0.001).ConclusionsThis Dutch registry study identified independent risk factors for DMEK graft detachment leading to rebubbling, namely recipient age and surgical complication, and early graft failure, namely transplantation before 2016 and surgical complication. Rebubbling was associated with significantly higher endothelial cell loss in the first year after surgery.
Evidence-based interventions to reduce mortality among preterm and low-birthweight neonates in low-income and middle-income countries: a systematic review and meta-analysis
Authors: Kleinhout Mirjam Y , Stevens Merel M , Osman Kwabena Aqyapong , Adu-Bonsaffoh Kwame , Groenendaal Floris , Biza Zepro Nejimu , Rijken Marcus J , Browne Joyce L 
Published: February 2021

BackgroundPreterm birth is the leading cause of under-five-mortality worldwide, with the highest burden in low-income and middle-income countries (LMICs). The aim of this study was to synthesise evidence-based interventions for preterm and low birthweight (LBW) neonates in LMICs, their associated neonatal mortality rate (NMR), and barriers and facilitators to their implementation. This study updates all existing evidence on this topic and reviews evidence on interventions that have not been previously considered in current WHO recommendations.MethodsSix electronic databases were searched until 3 March 2020 for randomised controlled trials reporting NMR of preterm and/or LBW newborns following any intervention in LMICs. Risk ratios for mortality outcomes were pooled where appropriate using a random effects model (PROSPERO registration number: CRD42019139267).Results1236 studies were identified, of which 49 were narratively synthesised and 9 contributed to the meta-analysis. The studies included 39 interventions in 21 countries with 46 993 participants. High-quality evidence suggested significant reduction of NMR following antenatal corticosteroids (Pakistan risk ratio (RR) 0.89; 95% CI 0.80 to 0.99|Guatemala 0.74; 0.68 to 0.81), single cord (0.65; 0.50 to 0.86) and skin cleansing with chlorhexidine (0.72; 0.55 to 0.95), early BCG vaccine (0.64; 0.48 to 0.86; I20%), community kangaroo mother care (OR 0.73; 0.55 to 0.97; I20%) and home-based newborn care (preterm 0.25; 0.14 to 0.48|LBW 0.42; 0.27 to 0.65). No effects on perinatal (essential newborn care 1.02; 0.91 to 1.14|neonatal resuscitation 0.95; 0.84 to 1.07) or 7-day NMR (essential newborn care 1.03; 0.83 to 1.27|neonatal resuscitation 0.92; 0.77 to 1.09) were observed after training birth attendants.ConclusionThe findings of this study encourage the implementation of additional, evidence-based interventions in the current (WHO) guidelines and to be selective in usage of antenatal corticosteroids, to reduce mortality among preterm and LBW neonates in LMICs. Given the global commitment to end all preventable neonatal deaths by 2030, continuous evaluation and improvement of the current guidelines should be a priority on the agenda.
Risk of acute deterioration and care complexity individual factors associated with health outcomes in hospitalised patients with COVID-19: a multicentre cohort study
Authors: Adamuz Jordi , González-Samartino Maribel , Jiménez-Martínez Emilio , Tapia-Pérez Marta , López-Jiménez María-Magdalena , Rodríguez-Fernández Hugo , Castro-Navarro Trinidad , Zuriguel-Pérez Esperanza , Carratala Jordi , Juvé-Udina Maria-Eulàlia 
Published: February 2021

BackgroundEvidence about the impact of systematic nursing surveillance on risk of acute deterioration of patients with COVID-19 and the effects of care complexity factors on inpatient outcomes is scarce. The aim of this study was to determine the association between acute deterioration risk, care complexity factors and unfavourable outcomes in hospitalised patients with COVID-19.MethodsA multicentre cohort study was conducted from 1 to 31 March 2020 at seven hospitals in Catalonia. All adult patients with COVID-19 admitted to hospitals and with a complete minimum data set were recruited retrospectively. Patients were classified based on the presence or absence of a composite unfavourable outcome (in-hospital mortality and adverse events). The main measures included risk of acute deterioration (as measured using the VIDA early warning system) and care complexity factors. All data were obtained blinded from electronic health records. Multivariate logistic analysis was performed to identify the VIDA score and complexity factors associated with unfavourable outcomes.ResultsOut of a total of 1176 patients with COVID-19, 506 (43%) experienced an unfavourable outcome during hospitalisation. The frequency of unfavourable outcomes rose with increasing risk of acute deterioration as measured by the VIDA score. Risk factors independently associated with unfavourable outcomes were chronic underlying disease (OR: 1.90, 95% CI 1.32 to 2.72; p<0.001), mental status impairment (OR: 2.31, 95% CI 1.45 to 23.66; p<0.001), length of hospital stay (OR: 1.16, 95% CI 1.11 to 1.21; p<0.001) and high risk of acute deterioration (OR: 4.32, 95% CI 2.83 to 6.60; p<0.001). High-tech hospital admission was a protective factor against unfavourable outcomes (OR: 0.57, 95% CI 0.36 to 0.89; p=0.01).ConclusionThe systematic nursing surveillance of the status and evolution of COVID-19 inpatients, including the careful monitoring of acute deterioration risk and care complexity factors, may help reduce deleterious health outcomes in COVID-19 inpatients.
Concurrent prescriptions for opioids and benzodiazepines and risk of opioid overdose: protocol for a retrospective cohort study using linked administrative data
Authors: Liu Erin Y , Tamblyn Robyn , Filion Kristian B , Buckeridge David L 
Published: February 2021

IntroductionOpioid overdoses have increased substantially over the last 20 years, with over 400 000 deaths in North America. While opioid prescribing has been a target of research, benzodiazepine and opioid co-intoxication has emerged as a potential risk factor. Our aim was to assess the risk of opioid overdose associated with concurrent use of opioids and benzodiazepines relative to opioids alone.Methods and analysisA retrospective cohort study will be conducted using medical claims data from adult residents of Montréal, Canada. We will create a cohort of new users of opioids (ie, no opioid dispensations in prior year) in 2000–2014 from people with at least 2 years of continuous health insurance. Those with any diagnosis or hospitalisation for cancer or palliative care in the 2 years before their first opioid dispensation will be excluded. On each person-day of follow-up, exposure status will be classified into one of four mutually exclusive categories: (1) opioid-only, (2) benzodiazepine-only, (3) both opioid and benzodiazepine (concurrent use) or (4) neither. Opioid overdose will be measured using diagnostic codes documented in the hospital discharge abstract database, physician billing claims from emergency department visits and death records. Using a marginal structural Cox proportional hazards model, we will compare the hazard of overdose during intervals of concurrent opioid and benzodiazepine use to intervals of opioid use alone, adjusted for sociodemographics, medical and psychiatric comorbidities, and substance use disorders.Ethics and disseminationThis study is approved by the McGill Faculty of Medicine Institutional Review Board and theCommission d’access à l’information(Québec privacy commission). Results will be relevant to clinicians, policymakers and other researchers interested in co-prescribing practices of opioids and benzodiazepines. Study findings will be disseminated at relevant conferences and published in biomedical and epidemiological peer-reviewed journals.
Effectiveness of interventions to reduce COVID-19 transmission in a large urban jail: a model-based analysis
Authors: Malloy Giovanni S P , Puglisi Lisa , Brandeau Margaret L , Harvey Tyler D , Wang Emily A 
Published: February 2021

ObjectivesWe aim to estimate the impact of various mitigation strategies on COVID-19 transmission in a US jail beyond those offered in national guidelines.DesignWe developed a stochastic dynamic transmission model of COVID-19.SettingOne anonymous large urban US jail.ParticipantsSeveral thousand staff and incarcerated individuals.InterventionsThere were four intervention phases during the outbreak: the start of the outbreak, depopulation of the jail, increased proportion of people in single cells and asymptomatic testing. These interventions were implemented incrementally and in concert with one another.Primary and secondary outcome measuresThe basic reproduction ratio, R0, in each phase, as estimated using the next generation method. The fraction of new cases, hospitalisations and deaths averted by these interventions (along with the standard measures of sanitisation, masking and social distancing interventions).ResultsFor the first outbreak phase, the estimated R0 was 8.44 (95% credible interval (CrI): 5.00 to 13.10), and for the subsequent phases, R0,phase 2=3.64 (95% CrI: 2.43 to 5.11), R0,phase 3=1.72 (95% CrI: 1.40 to 2.12) and R0,phase 4=0.58 (95% CrI: 0.43 to 0.75). In total, the jail’s interventions prevented approximately 83% of projected cases, hospitalisations and deaths over 83 days.ConclusionsDepopulation, single celling and asymptomatic testing within jails can be effective strategies to mitigate COVID-19 transmission in addition to standard public health measures. Decision makers should prioritise reductions in the jail population, single celling and testing asymptomatic populations as additional measures to manage COVID-19 within correctional settings.
Emergency scalpel cricothyroidotomy use in a prehospital trauma service: a 20-year review
Authors: Aziz Shadman , Foster Elizabeth , Lockey David J , Christian Michael D 
Published: February 2021

BackgroundThis study aimed to determine the rate of scalpel cricothyroidotomy conducted by a physician–paramedic prehospital trauma service over 20 years and to identify indications for, and factors associated with the intervention.MethodsA retrospective observational study was conducted from 1 January 2000 to 31 December 2019 using clinical database records. This study was conducted in a physician–paramedic prehospital trauma service, serving a predominantly urban population of approximately 10 million in an area of approximately 2500 km2.ResultsOver 20 years, 37 725 patients were attended by the service, and 72 patients received a scalpel cricothyroidotomy. An immediate ‘primary’ cricothyroidotomy was performed in 17 patients (23.6%), and ‘rescue’ cricothyroidotomies were performed in 55 patients (76.4%). Forty-one patients (56.9%) were already in traumatic cardiac arrest during cricothyroidotomy. Thirty-two patients (44.4%) died on scene, and 32 (44.4%) subsequently died in hospital. Five patients (6.9%) survived to hospital discharge, and three patients (4.2%) were lost to follow-up. The most common indication for primary cricothyroidotomy was mechanical entrapment of patients (n=5, 29.4%). Difficult laryngoscopy, predominantly due to airway soiling with blood (n=15, 27.3%) was the most common indication for rescue cricothyroidotomy. The procedure was successful in 97% of cases. During the study period, 6570 prehospital emergency anaesthetics were conducted, of which 30 underwent rescue cricothyroidotomy after failed tracheal intubation (0.46%, 95% CI 0.31% to 0.65%).ConclusionsThis study identifies a number of indications leading to scalpel cricothyroidotomy both as a primary procedure or after failed intubation. The main indication for scalpel cricothyroidotomy in our service was as a rescue airway for failed laryngoscopy due to a large volume of blood in the airway. Despite high levels of procedural success, 56.9% of patients were already in traumatic cardiac arrest during cricothyroidotomy, and overall mortality in patients with trauma receiving this procedure was 88.9% in our service.
Impact of C-reactive protein flare-response on oncological outcomes in patients with metastatic renal cell carcinoma treated with nivolumab
Authors: Fukuda Shohei , Saito Kazutaka , Yasuda Yosuke , Kijima Toshiki , Yoshida Soichiro , Yokoyama Minato , Ishioka Junichiro , Matsuoka Yoh , Kageyama Yukio , Fujii Yasuhisa 
Published: February 2021

BackgroundThe dynamic change in C-reactive protein (CRP) levels, CRP kinetics, is a prognostic factor for metastatic renal cell carcinoma (mRCC) in the tyrosine kinase inhibitor era. We investigated the impact of early CRP kinetics on the efficacy of nivolumab in patients with mRCC.MethodsWe performed a retrospective analysis of 42 mRCC patients who were treated with nivolumab as a second-line or later therapy between 2016 and 2019. All patients had received previous TKI therapy. Patients were divided into three groups based on their early CRP kinetics: CRP levels increased to more than double compared with baseline within 1 month after initiation of nivolumab (flare) and then decreased to a lower value than baseline within 3 months (CRP flare-responders); CRP levels decreased by ≥30% within 3 months without “flare” (CRP responders); and the remaining patients (non-CRP responders). The maximum tumor shrinkage, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. The association of the early CRP kinetics and oncological outcomes was assessed.ResultsThe median follow-up period was 8 months. The median baseline CRP level was 23 mg/L. CRP flare-responders, CRP responders, and non-CRP responders included 11 (26%), 15 (36%), and 16 (38%) patients, respectively. Thirteen patients (31%) died of mRCC. The maximum changes in target lesions from baseline of CRP flare-responder, CRP-responder, and non-CRP responder groups were −38%, −13%, and 16%, on average, respectively (p<0.001). ORRs of these three groups were 73%, 27%, and 6%, respectively (p<0.001). The median PFS values of each group were not reached, 12 months, and 2.4 months (p=0.005), and the median OS values were not reached, not reached, and 12 months (p=0.048). In a multivariate analysis, early CRP kinetics was a significant independent factor for objective response, PFS, and OS (p<0.001, p=0.004, and p=0.006, respectively).ConclusionsCRP flare-response was associated with significant tumor shrinkage and improved survival outcomes in patients with mRCC who were treated with nivolumab. Early CRP kinetics could be useful for evaluating nivolumab treatment efficacy.
Price of a Finger
Authors: Van Carlen Martin , Ghini Francesca , Mallina Ravi , Jose Rajive 
Published: February 2021

Background: Traumatic loss of an index finger is offered twice the amount of compensation as compared to a loss of little finger. However, the little finger plays a pivotal role in power grip thus is underestimated in its importance. Our aim was to test our hypothesis that loss of the little finger will result in greater or equal loss of grip strength compared to loss of the index finger. Methods: Grip strength in the power grip position was measured in 12 healthy volunteers using a JAMAR hand dynamometer. Grip strength of their dominant hand was recorded as a mean kg force of three attempts in three grip configurations 1) using all fingers 2) excluding the index finger and 3) excluding the little finger. Grip strength percentage compared to the full hand was calculated and statistical significance was investigated with a two-tailed T-test. Results: Participants’ age varied from 19–64 years, with 4 males and 8 females. Mean full hand grip strength was 28.3 kg force; grip strength with index finger excluded was 65.8% and with little finger excluded was 66.2%. There was no significant difference in grip strength percentage when comparing index or little finger exclusion (p = 0.92). Conclusions: We did not find a difference in power grip using a simulated model of index or little finger loss in a healthy volunteer cohort. This should be taken into account in traumatic loss and work compensation.
Estimation of Synteny Conservation and Genome Compaction Between Pufferfish (Fugu) and Human
Authors: McLysaght Aoife , Enright Anton J. , Skrabanek Lucy , Wolfe Kenneth H. 
Published: February 2021

Background: Knowledge of the amount of gene order and synteny conservation between two species gives insights to the extent and mechanisms of divergence. The vertebrate Fugu rubripes (pufferfish) has a small genome with little repetitive sequence which makes it attractive as a model genome. Genome compaction and synteny conservation between human and Fugu were studied using data from public databases.Methods: Intron length and map positions of human and Fugu orthologues were compared to analyse relative genome compaction and synteny conservation respectivley. The divergence of these two genomes by genome rearrangement was simulated and the results were compared to the real data.Results: Analysis of 199 introns in 22 orthologous genes showed an eight-fold average size reduction in Fugu, consistent with the ratio of total genome sizes. There was no consistent pattern relating the size reduction in individual introns or genes to gene base composition in either species. For genes that are neighbours in Fugu (genes from the same cosmid or GenBank entry), 40–50% have conserved synteny with a human chromosome. This figure may be underestimated by as much as two-fold, due to problems caused by incomplete human genome sequence data and the existence of dispersed gene families. Some genes that are neighbours in Fugu have human orthologues that are several megabases and tens of genes apart. This is probably caused by small inversions or other intrachromosomal rearrangements.Conclusions: Comparison of observed data to computer simulations suggests that 4000–16 000 chromosomal rearrangements have occured since Fugu and human shared a common ancestor, implying a faster rate of rearrangement than seen in human/mouse comparisons.
GAS7 Deficiency Promotes Metastasis in MYCN-Driven Neuroblastoma
Authors: Dong Zhiwei , Yeo Kok Siong , Lopez Gonzalo , Zhang Cheng , Dankert Eggum Erin N. , Rokita Jo Lynne , Ung Choong Yong , Levee Taylor M. , Her Zuag Paj , Howe Cassie J. , Hou Xiaonan , van Ree Janine H. , Li Shuai , He Shuning , Tao Ting , Fritchie Karen , Torres-Mora Jorge , Lehman Julia S. , Meves Alexander , Razidlo Gina L. , Rathi Komal S. , Weroha S. John , Look A. Thomas , van Deursen Jan M. , Li Hu , Westendorf Jennifer J. , Maris John M. , Zhu Shizhen 
Published: February 2021

AbstractOne of the greatest barriers to curative treatment of neuroblastoma is its frequent metastatic outgrowth prior to diagnosis, especially in cases driven by amplification of the MYCN oncogene. However, only a limited number of regulatory proteins that contribute to this complex MYCN-mediated process have been elucidated. Here we show that the growth arrest-specific 7 (GAS7) gene, located at chromosome band 17p13.1, is preferentially deleted in high-risk MYCN-driven neuroblastoma. GAS7 expression was also suppressed in MYCN-amplified neuroblastoma lacking 17p deletion. GAS7 deficiency led to accelerated metastasis in both zebrafish and mammalian models of neuroblastoma with overexpression or amplification of MYCN. Analysis of expression profiles and the ultrastructure of zebrafish neuroblastoma tumors with MYCN overexpression identified that GAS7 deficiency led to (i) downregulation of genes involved in cell–cell interaction, (ii) loss of contact among tumor cells as critical determinants of accelerated metastasis, and (iii) increased levels of MYCN protein. These results provide the first genetic evidence that GAS7 depletion is a critical early step in the cascade of events culminating in neuroblastoma metastasis in the context of MYCN overexpression.Significance:Heterozygous deletion or MYCN-mediated repression of GAS7 in neuroblastoma releases an important brake on tumor cell dispersion and migration to distant sites, providing a novel mechanism underlying tumor metastasis in MYCN-driven neuroblastoma.See related commentary by Menard, p. 2815