bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors impacting the solo remote placement experiences of undergraduate James Cook University medical students: A mixed‐methods pilot study
Authors: Lane Angus , Woolley Torres , Sen Gupta Tarun , Stewart Ruth , Hollins Aaron , Harte Jane 
Published: December 2020

AbstractObjectiveTo determine the factors impacting the experiences of James Cook University medical students on solo placements in remote towns.DesignThis 2018 pilot study used an exploratory sequential mixed‐methods approach to explore the recent solo remote placement experiences of James Cook University medical students. Qualitative interviews were performed initially to elicit context sensitive themes for the self administered survey. The survey went on to use Likert‐scale questions in addition to pre‐validated survey instruments.SettingFocus groups and interviews took place at James Cook University Medical School in Townsville in late 2018 after students returned from their rural rotation. Two telephone interviews were conducted for Year 6 students unable to attend the focus groups.ParticipantsJames Cook University medical students in years 2, 4 and 6 students who experienced a solo placement in a remote (MMM 6 or 7) town during 2017 or 2018 were invited to be part of the study. Only Townsville‐based students were involved. A total of 14 students participated in the focus groups (n = 14) and a further 31 students completed the survey (n = 31).Main outcome measure(s)Interviews identified themes negatively or positively impacting solo remote placement experience, while bivariate analysis identified factors associated with having an ‘excellent’ overall experience.ResultsStudent interviews identified five main themes impacting student experience in remote communities: culture of the medical facility; quality and quantity of clinical experiences; quality of accommodation; placement length; and community infrastructure and services. Negative impacts could result in students experiencing social isolation. Students reporting an ‘excellent’ solo remote placement experience in the survey were more likely to have: felt very welcome in the community; felt the health staff supported them; heavily involved themselves in clinical activities; enjoyed the experiences remote communities can offer; positive rural career intentions; reported they ‘bounce back during and after life's most stressful events’; and come from a rural or remote hometown.ConclusionsSolo remote placements provide medical students with opportunities to further knowledge, clinical capabilities, social experiences and careers, but can have negative aspects. However, negative aspects are often modifiable management issues or can potentially be avoided if prospective students are better informed of the challenges associated with remote communities.
‘Biggest factors in having cancer were costs and no entitlement to compensation’—The determinants of out‐of‐pocket costs for cancer care through the lenses of rural and outer metropolitan Western Australians
Authors: Slavova‐Azmanova Neli S. , Newton Jade C. , Saunders Christobel , Johnson Claire E. 
Published: December 2020

AbstractObjectiveThe aim of this qualitative analysis was to determine patients’ perceptions of the impact of cancer‐related costs.DesignA qualitative inductive content analysis of the comment sections of surveys completed by participants in a cross‐sectional study of cancer‐related expenses.SettingResidents of 4 regional/rural and 2 outer metropolitan areas in Western Australia.ParticipantsAdults diagnosed with breast, prostate, colorectal or lung cancer participated in the study between 1 April 2014 and 31 April 2017.Main Outcome MeasuresThis study identified the key factors contributing to the cost experiences reported by the participants.ResultsParticipant comments were organised into 4 main categories perceived to incorporate the key factors contributing to the cost experiences reported by 300 participants: 1) health care system factors (access to care in the public or private sector, availability of services close to home, gap payments, cost of travel) 2) financial factors (impact of cancer on employment, ability to work, and career; and strategies for improving financial difficulties) 3) social and community support provided by the government and not‐for‐profit organisations and 4) understanding of the health care system.ConclusionThere is a need for cost transparency, initiatives for no‐ or low‐fee billing providers, access to care close to home, development of financial assistance schemes and return to work programs to alleviate the financial hardship experienced by cancer patients and their families.
Individual prediction of thrombocytopenia at next chemotherapy cycle: Evaluation of dynamic model performances
Authors: Kheifetz Yuri , Scholz Markus 
Published: December 2020

AimsThrombocytopenia is a common major side‐effect of cytotoxic cancer therapies. A clinically relevant problem is to predict an individual's thrombotoxicity in the next planned chemotherapy cycle in order to decide on treatment adaptation. To support this task, 2 dynamic mathematical models of thrombopoiesis under chemotherapy were proposed, a simple semimechanistic model and a comprehensive mechanistic model. In this study, we assess the performance of these models with respect to existing thrombocytopenia grading schemes.MethodsWe consider close‐meshed individual time series data of 135 non‐Hodgkin's lymphoma patients treated with 6 cycles of CHOP/CHOEP chemotherapies. Individual parameter estimates were derived on the basis of these data considering a varying number of cycles per patient. Parsimony assumptions were applied to optimize parameter identifiability. Models' predictability are assessed by determining deviations of predicted and observed degrees of thrombocytopenia in the next cycles.ResultsThe mechanistic model results in better agreement of model prediction and individual time series data. Prediction accuracy of future cycle toxicities by the mechanistic model is higher even if the semimechanistic model is provided with data of more cycles for calibration.ConclusionWe successfully established a quantitative and clinically relevant method for assessing prediction performances of biomathematical models of thrombopoiesis under chemotherapy. We showed that the more comprehensive mechanistic model outperforms the semimechanistic model. We aim at implementing the mechanistic model into clinical practice to assess its utility in real life clinical decision‐making.
Second‐hand smoke and NFE2L2 genotype interaction increases paediatric asthma risk and severity
Authors: Johansson Elisabet , Martin Lisa J. , He Hua , Chen Xiaoting , Weirauch Matthew T. , Kroner John W. , Khurana Hershey Gurjit K. , Biagini Jocelyn M. 
Published: December 2020

AbstractBackgroundSecond‐hand smoke (SHS) exposure is associated with paediatric asthma, and oxidative stress is believed to play a role in mediating this association. The nuclear factor (erythroid‐derived 2)‐like 2 (NFE2L2) is important for the defence against oxidative stress.ObjectiveTo explore interactions between NFE2L2 genotype and SHS exposure in paediatric asthma risk.MethodsWe used a genotyped subset of patients of European ancestry (N = 669, median age at enrolment = 6.8 years) enrolled in the clinical cohort Greater Cincinnati Pediatric Clinic Repository as the study population, and a population‐based paediatric cohort (N = 791) to replicate our findings. History of asthma diagnosis was obtained from medical records, and SHS exposure was obtained from questionnaires. Four NFE2L2 tagging SNPs were included in the analysis, and interactions between SHS and NFE2L2 genotype were evaluated using logistic regression.ResultsThree of the analysed SNPs, rs10183914, rs1806649 and rs2886161, interacted significantly with SHS exposure to increase asthma risk (p ≤ .02). The interaction was replicated in an independent cohort for rs10183914 (p = .04). Interactions between SHS exposure and NFE2L2 genotype were also associated with an increased risk of hospitalization (p = .016). In stratified analyses, NFE2L2 genotype was associated with daily asthma symptoms in children with SHS exposure (OR = 3.1; p = .048). No association was found in children without SHS exposure. Examination of publicly available chromatin immunoprecipitation followed by sequencing (ChIP‐seq) data sets confirmed the presence of active histone marks and binding sites for particular transcription factors overlapping the coordinates for the significantly associated SNPs.Conclusions and Clinical RelevanceOur study provides evidence that NFE2L2 genotype interacts with SHS exposure to affect both asthma risk and severity in children and identifies a population of children at increased risk of asthma development.
Multi‐centre study of the clinical features and gene variant spectrum of Gitelman syndrome in Chinese children
Authors: Shen Qian , Chen Jiemei , Yu Minghui , Lin Zhi , Nan Xiaojuan , Dong Beijun , Fang Xiaoyan , Chen Jing , Ding Guixia , Zhang Aihua , Gao Chunlin , Miao Li , Xu Yuanyuan , Jiang Xiaoyun , Bai Haitao , Zhuang Jieqiu , Gao Xiaojie , Xu Hong ,   for Chinese Children Genetic Kidney Disease Database (CCGKDD)
Published: December 2020

AbstractBased on the Chinese Children Genetic Kidney Disease Database (CCGKDD), we established a pediatric Gitelman syndrome (GS) cohort to explore the phenotype and genotype characteristics. Thirty‐two patients with SLC12A3 gene variants were collected. Five cases (16%) were homozygous, 16 (50%) were compound heterozygous, 10 (31%) carried only a single variant, and the other one harbored two de novo variants beyond classification. p.(T60M) was found in eight patients. The average diagnosis age was 7.79 ± 3.54 years. A total of 31% of the patients were asymptomatic. Muscle weakness was the most common symptom, accounting for 50%. Earlier age of onset (4.06 ± 1.17 yr vs. 8.10 ± 3.46 yr vs. 8.61 ± 3.56 yr, p< 0.05) and lower urinary calcium‐creatinine ratio (p = 0.024) were found in the homozygous group than those in the heterozygous and compound heterozygous group. Patients with p.(T60M) variant had an earlier age of onset (4.01 ± 2.83 yr vs. 6.92 ± 3.07 yr, p = 0.025) and lower urinary calcium‐creatinine ratio (p = 0.056). Thus, more than 30% of GS children have no clinical symptoms. Homozygous variant and the p.(T60M) variant may be associated with earlier onset and lower urinary calcium excretion in Chinese pediatric GS.
Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms
Authors: Huang Xiaowen , Hussain Basharat , Chang Junlei 
Published: December 2020

AbstractThe blood–brain barrier (BBB) is an important physiological barrier that separates the central nervous system (CNS) from the peripheral circulation, which contains inflammatory mediators and immune cells. The BBB regulates cellular and molecular exchange between the blood vessels and brain parenchyma. Normal functioning of the BBB is crucial for the homeostasis and proper function of the brain. It has been demonstrated that peripheral inflammation can disrupt the BBB by various pathways, resulting in different CNS diseases. Recently, clinical research also showed CNS complications following SARS‐CoV‐2 infection and chimeric antigen receptor (CAR)‐T cell therapy, which both lead to a cytokine storm in the circulation. Therefore, elucidation of the mechanisms underlying the BBB disruption induced by peripheral inflammation will provide an important basis for protecting the CNS in the context of exacerbated peripheral inflammatory diseases. In the present review, we first summarize the physiological properties of the BBB that makes the CNS an immune‐privileged organ. We then discuss the relevance of peripheral inflammation‐induced BBB disruption to various CNS diseases. Finally, we elaborate various factors and mechanisms of peripheral inflammation that disrupt the BBB.
Allergic contact dermatitis to phenol‐formaldehyde resin at a single tertiary dermatology centre
Authors: Dear Kate , Palmer Amanda , Nixon Rosemary L. 
Published: December 2020

AbstractBackgroundPhenol‐formaldehyde resin 2 (PFR2) has been shown to be a useful marker of contact allergy (CA) to various phenol‐formaldehyde resins. These compounds are used in several industries as solids, powders, or semisolid resins, and are known to be sensitizing agents.ObjectivesThe aims were to investigate contact allergy to PFR2 in a single tertiary dermatology centre, to examine associated simultaneous allergic reactions, and to identify cases of allergic contact dermatitis (ACD) to PFR2.MethodsA retrospective study was performed of patients patch tested to PFR2 between 1 January 2003 and 17 June 2020.ResultsIn all, 337 of 7922 patients were tested to PFR2 and 16 (4.7%) reacted. Of those 16 individuals, six (37.5%) had a relevant reaction (1.8% of total). Simultaneous allergic reactions were noted to colophonium in eight (50.0%) patients,Myroxylon pereiraein five (31.3%), and fragrance mix I (FMI) of three cases (18.8%).ConclusionContact allergy to PFR2, even in a selected population of patients, is uncommon. However, patients exposed to plastics and glues, or who work with wood products should be routinely patch tested to a plastics and glues series containing PFR2. We recommend that all centres include PFR2 in their plastics and glues series.
Redefining the collateral system between the superior mesenteric artery and inferior mesenteric artery: a novel classification
Authors: Kuzu Mehmet Ayhan , Güner Mehmet Ali , Kocaay Akın Fırat , İsmail Erkin , Arslan Murat Nihat , Tekdemir İbrahim , Açar Halil İbrahim 
Published: December 2020

AbstractAimThe aim of this study was to evaluate the arterial collateral vasculature between the superior mesenteric artery and the inferior mesenteric artery (IMA) from a surgical perspective.MethodA total of 107 fresh adult cadavers (94 male) were studied with emphasis on the vascular anatomy of the left colon. Dissections were carried out mimicking the anterior resection technique. The vasculature of the left mesocolon and the collaterals between the superior mesenteric artery and the IMA with respect to their relationship to the inferior mesenteric vein (IMV) were assessed and classified. Collaterals were classified into three different groups: marginal anastomoses (via the marginal = pericolic artery), intermediate mesocolic anastomoses (parallel to the marginal artery but neither adjacent to the IMV nor close to the duodenum) and central mesocolic anastomoses (next to the IMV at the level of the duodenojejunal junction and the lower border of the pancreas).ResultsAll patients had a marginal anastomosis. However, the marginal anastomosis, as the only anastomosis between the superior and inferior mesenteric arteries at the splenic flexure, was observed in 41 cases (38%). In addition to the marginal artery, intermediate mesocolic anastomoses were found in 49 (46%) and a central mesocolic anastomosis was observed in 17 (16%) of the 107 cases in the splenic flexure mesocolon. It is in this latter variant that collateral vessels can be compromised during ligation/transection of the IMV.ConclusionThis new classification can contribute to a precise mesocolic dissection technique and splenic flexure mobilization and help prevent ischaemic damage to the descending colon.
A target‐mediated drug disposition population pharmacokinetic model of GC1118, a novel anti‐EGFR antibody, in patients with solid tumors
Authors: Chung Tae Kyu , Lee Hyun A. , Park Sang‐In , Oh Do‐Youn , Lee Keun‐Wook , Kim Jin Won , Kim Jee Hyun , Woo Ahmi , Lee Su Jin , Bang Yung‐Jue , Lee Howard 
Published: December 2020

AbstractGC1118 is a monoclonal antibody for epidermal growth factor receptor (EGFR) that is currently under clinical development to treat patients with solid tumors. In this study, the pharmacokinetics (PKs) of GC1118 were modeled in solid tumor patients who received a 2‐h intravenous infusion of GC1118 at 0.3, 1, 3, 5, or 4 mg/kg once‐weekly (Q1W) on days 1, 8, 15, and 22 or 8 mg/kg every other week on days 1 and 15. A target‐mediated drug disposition population PK model adequately described the concentration‐time profiles of GC1118. Monte‐Carlo simulation experiments of the PK profiles and EGFR occupancies (ROs) by GC1118 based on the final model showed that Q1W at 4 or 5 mg/kg will produce a better antitumor effect than Q2W at 8 mg/kg. Because GC1118 was safer at 4 mg/kg than 5 mg/kg in the phase I study, we suggest to test the 4 mg/kg Q1W regimen in further clinical trials with GC1118.
Study Highlights

WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

GC1118, a fully human IgG1 monoclonal antibody (mAb) for epidermal growth factor receptor (EGFR), showed a nonlinear pharmacokinetic (PK) profile in monkeys and humans. The total clearance of GC1118 decreased as the dose was increased up to 3–4 mg/kg in humans, beyond which it remained stable. The recommended phase II dose for GC1118 was 4 mg/kg intravenously infused over 2 h once weekly.

WHAT QUESTION DID THIS STUDY ADDRESS?
We developed a target‐mediated drug disposition (TMDD) population PK model that described the nonlinear PK profile of GC1118 in patients with solid tumors. We also simulated the PK profiles and receptor occupancies for different dosage regimens.

WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
The TMDD population PK model adequately described the nonlinear and multiphasic PK profiles of GC1118 in humans. The simulation experiment showed that once‐weekly GC1118 at 4–5 mg/kg could be more efficacious than the biweekly regimen at 8 mg/kg.

HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
The pharmacometrics analysis could support better informed drug development decisions for GC1118, particularly for determining an optimal dosage regimen.
Indicators of dementia disease progression in primary care: An electronic health record cohort study
Authors: Rathod‐Mistry Trishna , Marshall Michelle , Campbell Paul , Bailey James , Chew‐Graham Carolyn A. , Croft Peter , Frisher Martin , Hayward Richard , Negi Rashi , Robinson Louise , Singh Swaran , Sumathipala Athula , Thein Nwe , Walters Kate , Weich Scott , Jordan Kelvin P. 
Published: December 2020

AbstractBackground and purposeThe objectives were to assess the feasibility and validity of using markers of dementia‐related health as indicators of dementia progression in primary care, by assessing the frequency with which they are recorded and by testing the hypothesis that they are associated with recognised outcomes of dementia. The markers, in 13 domains, were derived previously through literature review, expert consensus, and analysis of regional primary care records.MethodsThe study population consisted of patients with a recorded dementia diagnosis in the Clinical Practice Research Datalink, a UK primary care database linked to secondary care records. Incidence of recorded domains in the 36 months after diagnosis was determined. Associations of recording of domains with future hospital admission, palliative care, and mortality were derived.ResultsThere were 30,463 people with diagnosed dementia. Incidence of domains ranged from 469/1000 person‐years (Increased Multimorbidity) to 11/1000 (Home Pressures). An increasing number of domains in which a new marker was recorded in the first year after diagnosis was associated with hospital admission (hazard ratio for ≥4 domains vs. no domains = 1.24; 95% confidence interval = 1.15–1.33), palliative care (1.87; 1.62–2.15), and mortality (1.57; 1.47–1.67). Individual domains were associated with outcomes with varying strengths of association.ConclusionsFeasibility and validity of potential indicators of progression of dementia derived from primary care records are supported by their frequency of recording and associations with recognised outcomes. Further research should assess whether these markers can help identify patients with poorer prognosis to improve outcomes through stratified care and targeted support.
Comparison of chlorhexidine and alcohol‐based antisepsis of the distal limbs of horses
Authors: Doyle Aimie J. , Saab Matthew E. , Lewis Krystina M. , McClure J Trenton 
Published: December 2020

AbstractBackgroundAn alcohol‐based rub has been confirmed effective at reducing bacterial counts on equine skin. Skin sites with expected high bacterial burden have not been tested or has a comparison to a common protocol been performed.ObjectivesTo determine if ethanol‐based antisepsis reduces bacterial counts on the equine distal limb comparable to a current chlorhexidine scrub method and determine the most effective application technique for the product.Study designRandomised trial.MethodsForty‐one horses were used in the study. By horse, each limb was randomly assigned to a treatment group: 5min scrub using 4% chlorhexidine gluconate to a clipped site (CHG); 90s scrub using 80% ethanol to a clipped site (ETC); 90s contact with 80% ethanol applied as a spray to a clipped site (ETS) and 90s scrub using 80% ethanol to an unclipped site (ETUC). Samples were collected pre‐ and post‐treatment and plated in duplicate. Bacterial counts were log10 transformed and averaged between duplicates. A linear mixed model was used to compare mean log10 CFU/mL reduction between groups. A cost‐benefit analysis was performed.ResultsThere was no significant difference in mean log10 CFU/mL reduction between CHG and ETC in either fore‐ or hindlimbs. In forelimbs, there was no significant difference in mean log10 CFU/mL reduction between any groups. In hindlimbs, CHG had significantly greater mean log10 CFU/mL reduction than ETUC and ETS. No significant difference in cost‐benefit was found between CHG and ETC. Significant differences were noted between CHG and both ETUC and ETS.Main limitationsResearchers were not blinded to treatment group during sample collection.ConclusionsThis study showed no significant difference in reduction in bacterial counts on the distal limb of horses between CHG and ethonol (ET) when applied as a scrub to a clipped site and there was no significant difference in cost‐benefit between these treatments.