bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between biological and sociodemographic risks for developmental vulnerability in twins at age 5: a population data linkage study in Western Australia
Authors: Dhamrait Gursimran Kaur , Christensen Daniel , Pereira Gavin , Taylor Catherine Louise 
Published: October 2020

ObjectiveTo investigate the prevalence of, and associations between, prenatal and perinatal risk factors and developmental vulnerability in twins at age 5.DesignRetrospective cohort study using bivariate and multivariable logistic regression.SettingWestern Australia (WA), 2002–2015.Participants828 twin pairs born in WA with an Australian Early Development Census (AEDC) record from 2009, 2012 or 2015.Main outcome measuresThe AEDC is a national measure of child development across five domains. Children with scores <10th percentile were classified as developmentally vulnerable on, one or more domains (DV1), or two or more domains (DV2).ResultsIn this population, 26.0% twins were classified as DV1 and 13.5% as DV2. In the multivariable model, risk factors for DV1 were maternal age <25 years (adjusted OR (aOR): 7.06, 95% CI: 2.29 to 21.76), child speaking a language other than English at home (aOR: 6.45, 95% CI: 2.17 to 19.17), male child (aOR: 5.08, 95% CI: 2.89 to 8.92), age younger than the reference category for the study sample (≥5 years 1 month to <5 years 10 months) at time of AEDC completion (aOR: 3.34, 95% CI: 1.55 to 7.22) and having a proportion of optimal birth weight (POBW) <15th percentile of the study sample (aOR: 2.06, 95% CI 1.07 to 3.98). Risk factors for DV2 were male child (aOR: 7.87, 95% CI: 3.45 to 17.97), maternal age <25 (aOR: 5.60, 95% CI: 1.30 to 24.10), age younger than the reference category (aOR: 5.36, 95% CI: 1.94 to 14.82), child speaking a language other than English at home (aOR: 4.65, 95% CI: 1.14 to 19.03), mother’s marital status as not married at the time of twins’ birth (aOR: 4.59, 95% CI: 1.13 to 18.55), maternal occupation status in the lowest quintile (aOR: 3.30, 95% CI: 1.11 to 9.81) and a POBW <15th percentile (aOR: 3.11, 95% CI: 1.26 to 7.64).ConclusionBoth biological and sociodemographic risk factors are associated with developmental vulnerability in twins at 5 years of age.
Impact of incarceration on cardiovascular disease risk factors: a systematic review and meta-regression on weight and BMI change
Authors: Bondolfi Constantin , Taffe Patrick , Augsburger Aurélie , Jaques Cécile , Malebranche Mary , Clair Carole , Bodenmann Patrick 
Published: October 2020

ObjectiveCardiovascular disease is an underappreciated issue in prison medicine. Recent studies have revealed a higher prevalence of cardiovascular disease risk factors (CVDRFs) among individuals in prison, but the impact of incarceration on CVDRFs over time is not well understood. This review aimed to assess available literature and quantify the relationship between incarceration and trends in major CVDRFs in high-income countries.DesignSystematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Meta-regression on weight change and obesity.Data sourcesMedline, Embase, PubMed, Cochrane Central Wiley and Web of Science.Eligibility criteria for selecting studiesLongitudinal studies reporting on the incidence of, or trends in any CVDRF among current or former people in prison over time, in high-income countries.Data extraction and synthesisTwo authors independently screened articles for eligibility, extracted data and assessed quality using an adapted version of the Newcastle-Ottawa Scale. Trends in CVDRFs during and following incarceration were summarised and in those with sufficient data a meta-regression was performed.ResultsTwenty-six articles were identified. CVDRFs assessed included obesity, hypertension, diabetes, dyslipidaemia, tobacco use, physical inactivity and unhealthy diet. A meta-regression on change in weight during incarceration found a mean increase of 5.3 kg (95% CI 0.5 to 10.1) and change in body mass index of 1.8 kg/m2 (95% CI −0.9 to 4.6) at 2 years. Weight gain appeared most pronounced right after entering prison and then plateaued at 2 years. Concerning hypertension, the results were inconclusive, despite a trend towards rising blood pressure or prevalence of hypertension during incarceration, and an increased incidence of hypertension following incarceration. Results are contradictory or inconclusive for the other CVDRFs reviewed.ConclusionPossible explanations for the association between incarceration and weight include a sedentary lifestyle, unhealthy diet, forced smoking cessation, psychotropic medication use and high levels of stress. Incarceration may be an independent risk factor for cardiovascular disease.
Cohort profile: gastric cancer in the population-based, Finnish National Esophago-Gastric Cancer Cohort (FINEGO) Study
Authors: Kauppila Joonas H , Ohtonen Pasi , Rantanen Tuomo , Tyrväinen Tuula , Toikkanen Vesa , Pääaho Minna , Valtola Antti , Räsänen Jari , Kallio Raija , Sihvo Eero , Saarnio Juha , Karttunen Tuomo J , Pohjanen Vesa-Matti , Ristimäki Ari , Laine Simo , Kokkola Arto 
Published: October 2020

PurposeThe Finnish National Esophago-Gastric Cancer Cohort (FINEGO) was established with the aim of identifying factors that could contribute to improved outcomes in oesophago-gastric cancer. The aim of this study is to describe the patients with gastric cancer included in FINEGO.ParticipantsA total of 10 457 patients with gastric cancer or tumour diagnosis in the Finnish Cancer Registry or the Finnish Patient Registry during 1987–2016 were included in the cohort, with follow-up from Causes of Death Registry until 31 December 2016. All of the participants were at least 18 years of age, and had undergone either resectional or endoscopic mucosal surgery with curative or palliative intent.Findings to dateOf the 10 457 patients, 90.1% were identified to have cancer in both cancer and patient registries. In all, the median age was 70 at the time of surgery, 54.5% of the patients were men and 64.4% had no comorbidities. Education data were available for 31.1% of the patients, of whom the majority had had <12 years of formal education. Of the 7798 with cancer staging data available, 41.1% had a local cancer. Adenocarcinoma was the most common (94.2%) histological type. Almost all patients underwent open gastrectomy and 214% in hospitals with annual volume of more than 30 gastrectomies per year. A total of 8561 deaths occurred during the study period, of which 6474 were due to oesophago-gastric cancers. The 5-year survival was 34.6% and 5-year cancer-specific survival was 39.7%.Future plansThe data in FINEGO can be currently used for registry-based research but is being expanded by data extraction from patient records and scanning of histological samples from the Finnish biobanks. Initially, we are planning on studies on the national trends in treatment and mortality, and studies on the demographic factors and their influence on survival.
Protocol of a prospective, multicentre phase I study to evaluate the safety, tolerability and preliminary efficacy of the bispecific PSMAxCD3 antibody CC-1 in patients with castration-resistant prostate carcinoma
Authors: Heitmann Jonas S , Walz Juliane S , Pflügler Martin , Kauer Joseph , Schlenk Richard F , Jung Gundram , Salih Helmut R 
Published: October 2020

IntroductionProstate cancer is the second most common cancer in men worldwide. When the disease becomes resistant to androgen-deprivation therapy, treatment options are sparse. To address the high medical need in castration-resistant prostate cancer (CRPC), we generated a novel PSMAxCD3 bispecific antibody termed CC-1. CC-1 binds to prostate-specific membrane antigen that is expressed on prostate cancer cells and tumour vessels, thereby allowing a dual anticancer effect.Methods and analysisThis first in human clinical study is a prospective and multicentre trial which enrols patients with metastatic CRPC after failure of established third-line therapy. CC-1 is applied after prophylactic interleukin-6 receptor blockade with tocilizumab (once 8 mg/kg body weight). Each patient receives at least one cycle of CC-1 over a time course of 7 days in an inpatient setting. If clinical benefit is observed, up to five additional cycles of CC-1 can be applied. The study is divided in two parts: (1) a dose escalation phase with intraindividual dose increase from 28 µg to the target dose of 1156 µg based on a modified fast titration design by Simonet alto determine safety, tolerability and the maximum tolerated dose (MTD) as primary endpoints and (2) a dose expansion phase with additional 14 patients on the MTD level of part (1) to identify first signs of efficacy. Secondary endpoints compromise overall safety, tumour response, survival and a translational research programme with, among others, the analysis of CC-1 half-life, the induced immune response, as well as the molecular profiling in liquid biopsies.Ethics and disseminationThe PSMAxCD3 study was approved by the Ethics Committee of The University Hospital Tübingen (100/2019AMG1) and the Paul-Ehrlich-Institut (3684/02). Clinical trial results will be published in peer-reviewed journals.Trial registration numbersClinicalTrials.gov Registry (NCT04104607) and ClinicalTrials.eu Registry (EudraCT2019-000238-20).
Triaging of respiratory protective equipment on the assumed risk of SARS-CoV-2 aerosol exposure in patient-facing healthcare workers delivering secondary care: a rapid review
Authors: Ramaraj Prashanth , Super Jonathan , Doyle Ruben , Aylwin Christopher , Hettiaratchy Shehan 
Published: October 2020

ObjectivesIn patient-facing healthcare workers delivering secondary care, what is the evidence behind UK Government personal protective equipment (PPE) guidance on surgical masks versus respirators for SARS-CoV-2 protection?DesignTwo independent reviewers performed a rapid review. Appraisal was performed using Critical Appraisal Skills Programme checklists and Grading of Recommendations, Assessment, Development and Evaluations methodology. Results were synthesised by comparison of findings and appraisals.Data sourcesMEDLINE, Google Scholar, UK Government COVID-19 website and grey literature.Eligibility criteriaStudies published on any date containing primary data comparing surgical facemasks and respirators specific to SARS-CoV-2, and studies underpinning UK Government PPE guidance, were included.ResultsOf 30 identified, only 3 laboratory studies of 14 different respirators and 12 surgical facemasks were found. In all three, respirators were significantly more effective than facemasks when comparing protection factors, reduction factors, filter penetrations, total inspiratory leakages at differing particle sizes, mean inspiratory flows and breathing rates. Tests included live viruses and inert particles on dummies and humans. In the six clinical studies (6502 participants) included the only statistically significant result found continuous use of respirators more effective in clinical respiratory illness compared with targeted use or surgical facemasks. There was no consistent definition of ‘exposure’ to determine the efficacy of respiratory protective equipment (RPE). It is difficult to define ‘safe’.ConclusionsThere is a paucity of evidence on the comparison of facemasks and respirators specific to SARS-CoV-2, and poor-quality evidence in other contexts. The use of surrogates results in extrapolation of non-SARS-CoV-2 specific data to guide UK Government PPE guidance. The appropriateness of this is unknown given the uncertainty over the transmission of SARS-CoV-2.This means that the evidence base for UK Government PPE guidelines is not based on SARS-CoV-2 and requires generalisation from low-quality evidence of other pathogens/particles. There is a paucity of high-quality evidence regarding the efficacy of RPE specific to SARS-CoV-2. UK Government PPE guidelines are underpinned by the assumption of droplet transmission of SARS-CoV-2.These factors suggest that the triaging of filtering face piece class 3 respirators might increase the risk of COVID-19 faced by some.
Cessation of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation
Authors: Middeldorp Melissa E , Gupta Aashray , Elliott Adrian , Kadhim Kadhim , Thiyagarajah Anand , Gallagher Celine , Hendriks Jeroen , Linz Dominik , Emami Mehrdad , Mahajan Rajiv , Lau Dennis , Sanders Prashanthan 
Published: October 2020

ObjectiveTo characterise the rate, causes and predictors of cessation of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF).Patients and methodsConsecutive patients with AF with a long-term anticoagulation indication treated with NOACs (dabigatran, apixaban and rivaroxaban) in our centre from September 2010 through December 2016 were included. Prospectively collected data with baseline characteristics, causes of cessation, mean duration-to-cessation and predictors of cessation were analysed.ResultsThe study comprised 1415 consecutive patients with AF, of whom 439 had a CHA2DS2-VASc≥1 and were on a NOAC. Mean age was 71.9±8.7 years and 37% were females. Over a median follow-up of 3.6 years (IQR=2.7–5.3), 147 (33.5%) patients ceased their index-NOAC (113 switched to a different form of OAC), at a rate of 8.8 per 100 patient-years. Serious adverse events warranting NOAC cessation occurred in 28 patients (6.4%) at a rate of 1.6 events per 100 patient-years. The mean duration-to-cessation was 4.9 years (95% CI 4.6 to 5.1) and apixaban had the longest duration-to-cessation with (5.1, 95% CI 4.8 to 5.4) years, compared with dabigatran (4.6, 95% CI 4.2 to 4.9) and rivaroxaban (4.5, 95% CI 3.9 to 5.1), pairwise log-rank p=0.002 and 0.025, respectively. In multivariable analyses, age was an independent predictor of index-NOAC cessation (HR 1.03, 95% CI 1.01 to 1.05; p=0.006). Female gender (HR 2.2, 95% CI 1.04 to 4.64; p=0.04) independently predicted serious adverse events.ConclusionIn this ‘real world’ cohort, NOAC use is safe and well-tolerated when prescribed in an integrated care clinic. Whether apixaban is better tolerated compared with other NOACs warrants further study.
Cardiovascular disease recurrence and long-term mortality in a tri-ethnic British cohort
Authors: Vyas Manav V , Chaturvedi Nish , Hughes Alun D , Marmot Michael , Tillin Therese 
Published: October 2020

ObjectiveEthnic differences in cardiovascular disease incidence, but not cardiovascular disease recurrence, are reported. We characterised long-term risk of major adverse cardiovascular event (MACE) and mortality following a non-fatal cardiovascular event in a British cohort of South Asians, African Caribbeans and Europeans.MethodsWe identified index and recurrent cardiovascular events and mortality between 1988 and 2017 using hospital records and death registry. Using multivariable hazards models, we separately calculated the adjusted HR of MACE and death following index event, adjusting for demographics, vascular and lifestyle risk factors. Using interaction terms, we evaluated if decade of index event modified the association between ethnicity and outcomes.ResultsSouth Asians were younger at the index event (median age 66 years, n=396) than Europeans (69 years, n=335) and African Caribbeans (70 years, n=70). During 4228 person-years, of the 801 patients, 537 developed MACE and 338 died, with the highest crude rate of MACE in South Asians. On adjustment of baseline factors, compared with the Europeans, the higher risk of MACE (HR 0.97, 95% CI 0.77 to 1.21) and the lower risk of mortality (HR 0.95, 95% CI 0.72 to 1.26) in South Asians was eliminated. African Caribbeans had similar outcomes to Europeans (HR MACE 1.04, 95% CI 0.74 to 1.47; and HR death 1.07, 95% CI 0.70 to 1.64). Long-term survival following an index event improved in South Asians (ptrend 0.02) and African Caribbeans (ptrend 0.07) compared with Europeans.ConclusionsBaseline vascular risk factors explained the observed ethnic variation in cardiovascular disease recurrence and long-term mortality, with a relative improvement in survival of minority ethnic groups over time.
Axitinib plus avelumab in the treatment of recurrent glioblastoma: a stratified, open-label, single-center phase 2 clinical trial (GliAvAx)
Authors: Awada Gil , Ben Salama Laila , De Cremer Jennifer , Schwarze Julia Katharina , Fischbuch Lydia , Seynaeve Laura , Du Four Stephanie , Vanbinst Anne-Marie , Michotte Alex , Everaert Hendrik , Rogiers Anne , Theuns Peter , Duerinck Johnny , Neyns Bart 
Published: October 2020

BackgroundNo treatment demonstrated to improve survival in patients with recurrent glioblastoma (rGB) in a randomized trial. Combining axitinib with the programmed cell death ligand 1 blocking monoclonal antibody avelumab may result in synergistic activity against rGB.MethodsAdult patients with rGB following prior surgery, radiation therapy and temozolomide chemotherapy were stratified according to their baseline use of corticosteroids. Patients with a daily dose of ≤8 mg of methylprednisolone (or equivalent) initiated treatment with axitinib (5 mg oral two times per day) plus avelumab (10 mg/kg intravenous every 2 weeks) (Cohort-1). Patients with a higher baseline corticosteroid dose initiated axitinib monotherapy; avelumab was added after 6 weeks of therapy if the corticosteroid dose could be tapered to ≤8 mg of methylprednisolone (Cohort-2). Progression-free survival at 6 months (6-m-PFS%), per immunotherapy response assessment for neuro-oncology criteria, served as the primary endpoint.ResultsBetween June 2017 and August 2018, 54 patients (27 per cohort) were enrolled and initiated study treatment (median age: 55 years; 63% male; 91% Eastern Cooperative Oncology Group Performance Status 0–1). Seventeen (63%) patients treated in Cohort-2 received at least one dose of avelumab. The 6-m-PFS% was 22.2% (95% CI 6.5% to 37.9%) and 18.5% (95% CI 3.8% to 33.2%) in Cohort-1 and Cohort-2, respectively; median overall survival was 26.6 weeks (95% CI 20.8 to 32.4) in Cohort-1 and 18.0 weeks (95% CI 12.5 to 23.5) in Cohort-2. The best objective response rate was 33.3% and 22.2% in Cohort-1 and Cohort-2, respectively, with a median duration of response of 17.9 and 19.0 weeks. The most frequent treatment-related adverse events were dysphonia (67%), lymphopenia (50%), arterial hypertension and diarrhea (both 48%). There were no grade 5 adverse events.ConclusionThe combination of avelumab plus axitinib has an acceptable toxicity profile but did not meet the prespecified threshold for activity justifying further investigation of this treatment in an unselected population of patients with rGB.
Drug-coated balloon for vertebral artery origin stenosis: a pilot study
Authors: Wang Yabing , Feng Yiding , Wang Tao , Ma Yan , Gao Peng , Chen Jian , Chen Yanfei , Yang Bin , Jiao Liqun 
Published: October 2020

BackgroundDrug-coated balloon (DCB) is a potential treatment for patients with low restenosis risk in vertebral artery origin stenosis (VAOS). However, the clinical data of long-term outcome are limited.ObjectiveTo evaluate the safety and efficacy of a DCB in patients with severe VAOS.MethodsA prospective, non-randomized, single-center pilot study enrolled 30 patients with severe VAOS treated with DCB between 2017 and 2018. The first 20 patients were treated with a balloon-to-vessel ratio of predilation (pBVR)＜0.8 (small-size balloon predilation) and the following 10 patients were treated with a pBVR 0.8–1.0 (large-size balloon predilation). Primary safety endpoints included 30-day death, stroke, and transient ischemic attack (TIA). The main efficacy outcome was restenosis at 6 months, defined as a peak systolic velocity >140 cm/s measured by Doppler ultrasound. Long-term outcomes, including TIAs, stroke, death, and modified Rankin Scale score, were followed up to 2 years.ResultsTechnical success (<50% residual stenosis) was achieved in 26 patients (mean age 66.2±7.0; seven women). Four patients received bailout stenting and were excluded. Ultrasound confirmed restenosis at 6 months in 10 (38.5%) of 26, which was significantly less frequent in LSBP (LSBP vs SSBP=10% vs 56.3%, p<0.05). No adverse events occurred within 30 days of treatment. 19 patients were followed up for 2 years, with two deaths due to cancer.ConclusionThis pilot study suggests that DCB is a safe approach for VAOS. The relatively low restenosis rate indicates the its potential long-term efficacy for VAOS. Future randomized controlled trials to confirm its efficacy are warranted.
Thirteen‐month duration of immunity of an oral canine vaccine against challenge with Bordetella bronchiseptica
Authors: Scott‐Garrard Maya , Wang Xinshuo , Chiang Yu‐Wei , David Frederic 
Published: October 2020

BackgroundVery few studies have evaluated the duration of immunity of Bordetella bronchiseptica vaccines in dogs, and to date, no studies have been published on the duration of immunity of oral canine Bordetella bronchiseptica vaccines. This study was designed to determine the effectiveness of a single dose of an oral B bronchiseptica vaccine in dogs when challenged 13 months after vaccination.MethodsTwo groups of approximately eight‐week‐old beagles were vaccinated once with 1 ml of placebo vaccine (oral, n=17) or 1 ml of Recombitek Oral Bordetella (oral, n=17). Thirteen months after vaccination, both groups were challenged with virulent B bronchiseptica via aerosolisation.ResultsThirteen of 17 dogs in the placebo group (76.5 per cent) and no dogs in the Recombitek Oral Bordetella vaccine group (0.0 per cent) developed spontaneous cough of two or more consecutive days (disease case definition). Dogs in the Recombitek Oral Bordetella group had a significantly lower prevalence of disease with prevented fraction of 1 (100 per cent prevention). In addition, the number of days coughing, duration of cough and prevalence of tracheal and nasal shedding were significantly lower for dogs vaccinated with Recombitek Oral Bordetella.ConclusionsThe study demonstrated that vaccination with Recombitek Oral Bordetella is effective in preventing disease and reducing shedding 13 months after vaccination when compared with dogs vaccinated with a placebo.
Evolving the core microbial community in pit mud based on bioturbation of fortified Daqu
Authors: Chen Suqi , Huang Jun , Qin Hui , He Guiqiang , Zhou Rongqing , Yang Yan , Qiu Chuanfeng , Zhang Suyi 
Published: October 2020

Directional stress is an effective measure to change the community structure and improve the bioactivity of pit mud (PM). In this study, the addition of fortified Daqu to artificial PM (APM) was intended to disturb the microbial community and further affect metabolites. To evaluate the effect of fortified Daqu on culturing APM, the microbial communities of APM with or without the addition of fortified Daqu were investigated by fluorescence in situ hybridization and Illumina MiSeq. The results indicated that microbes (Clostridium sp., Clostridium kluyveri, hydrogenotrophic methanogens, and acetotrophic methanogens) related to the production of key aroma compounds increased notably when fortified Daqu was added. In particular, the hydrogenotrophic and acetotrophic methanogens increased by 6.19- and 4.63-fold after 30 days of culture. Subsequently, metabolites (organic acids, volatile compounds) were also analyzed by HPLC (high-performance liquid chromatography) and HS-SPME–GC–MS (headspace solid phase microextraction – gas chromatography – mass spectrometry). The results showed that the content of butyric acid and hexanoic acid was significantly higher when fortified Daqu was added to APM. In addition, the proportion of esters and phenols was also higher than in APM without fortified Daqu. A survey of the microbial compositions of APMs with or without added fortified Daqu indicated that the microbial community evolves into a functional community favoring liquor brewing. We have developed a novel process by disturbing the community diversity.