bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial
Authors: Hague William M. , Callaway Leonie , Chambers Jennifer , Chappell Lucy , Coat Suzette , de Haan-Jebbink Jiska , Dekker Marloes , Dixon Peter , Dodd Jodie , Fuller Maria , Gordijn Sanne , Graham Dorothy , Heikinheimo Oskari , Hennessy Annemarie , Kaaja Risto , Khong Teck Yee , Lampio Laura , Louise Jennie , Makris Angela , Markus Corey , Marschall Hanns-Ulrich , Middleton Philippa , Mol Ben W. , Morris Jonathan , Newnham John P. , Ovadia Caroline , Peek Michael , Shand Antonia , Stark Michael , Thornton Jim , Timonen Susanna , Walker Susan , Warrilow David , Williamson Catherine 
Published: January 2021

Abstract
Background
Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders.
Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach.

Methods
We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool.

Discussion
Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing “standard” UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial.

Trial identifiers
Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018).
HREC No: HREC/18/WCHN/36.
EudraCT number: 2018–004011-44.
IRAS: 272398.
NHMRC registration: APP1152418 and APP117853.
Apgar score and neonatal mortality in China: an observational study from a national surveillance system
Authors: Mu Yi , Li Mingrong , Zhu Jun , Wang Yanping , Xing Aiyun , Liu Zheng , Xie Yanxia , Wang Xiaodong , Liang Juan 
Published: January 2021

Abstract
Background
To examine the association between the Apgar score and neonatal mortality over gestational age in China and to explore whether this association changed when Apgar scores were combined at 1 and 5 min.

Methods
Data for all singleton live births collected from 438 hospitals between 2012 and 2016 were used in this study. Poisson regression with a robust variance estimator adjusted for a complete set of confounders was used to describe the strength of the association between the Apgar score and neonatal mortality.

Results
The relative risks of neonatal death-associated intermediate Apgar score at 5 min peaked at 39–40 weeks of gestation and subsequently decreased if the gestational age increased to 42 weeks or above, in contrast to the low Apgar score. Among both preterm and term new-borns with Apgar scores at 5 min, new-borns that were not small for gestational age had a lower mortality rate than those that were small for gestational age. The association between Apgar score and the neonatal mortality was even stronger when scores at 1 and 5 min were combined.

Conclusions
Apgar score is not only meaningful for preterm new-borns but also useful for term new-borns, especially term new-borns that are not small for gestational age. Once the baby’s Apgar score worsens, timely intervention is needed. There is still a gap between China and high-income countries in terms of sustained treatment of new-borns with low Apgar scores.
Clinical utility of liquid biopsy for EGFR driver, T790M mutation and EGFR amplification in plasma in patients with acquired resistance to afatinib
Authors: Oya Yuko , Yoshida Tatsuya , Asada Kazuhiro , Oguri Tetsuya , Inui Naoki , Morikawa Sayako , Ito Kentaro , Kimura Tomoki , Kunii Eiji , Matsui Takashi , Kubo Akihito , Kato Tatsuo , Abe Takashi , Tsuda Takeshi , Hida Toyoaki 
Published: January 2021

Abstract
Background
Cell-free DNA (cfDNA) genotyping in plasma using the cobas EGFR Mutation Test v2 (cobas) is the first liquid biopsy as a companion diagnosis to identify the EGFR T790M mutation (T790M) after the failure of treatment of EGFR-tyrosine kinase inhibitors (TKIs) (1st generation, gefitinib [G] and erlotinib [E] and 2nd generation, afatinib [A]). This study investigated the clinical utility of a liquid biopsy for patients who acquired resistance to afatinib.

Methods
We prospectively collected plasma from 51 patients who had acquired resistance to afatinib between April 2015 and November 2016 to evaluate the frequency of T790M by cobas and digital droplet PCR (UMIN000025112). Additionally, we retrospectively reviewed 38 patients who tested by cobas in plasma after G/E failure to compare for T790M detection between A and with G/E.

Results
The detection rate of EGFR-driver and T790M in plasma in patients treated with A (A group) as a first-line EGFR-TKI was lower than with G/E followed by A (G/E→A group), although the differences were not significant (EGFR-driver: 41% [A] vs. 67% [G/E→A], P=0.1867; and T790M: 8% [A] vs. 17% [G/E→A], P=0.5798). In first-line setting, the detection rate for EGFR-driver and T790M in plasma by cobas was lower in A group than in G/E group, although there was no significant difference (EGFR-driver: 34% [A] vs. 52% [G/E], P=0.2072; and T790M: 10% [A] vs. 27% [G/E], P=0.1161).

Conclusion
The detection of EGFR-driver and T790M in plasma by cobas in patients treated with afatinib might be lower than with G/E in a real-world setting.
Recent incidence trend of elderly patients with glioblastoma in the United States, 2000–2017
Authors: Chen Boran , Chen Chaoyue , Zhang Yang , Xu Jianguo 
Published: January 2021

Abstract
Background
The incidence of glioblastoma increases significantly with age. With the growing and aging population, there is a lack of comprehensive analysis of recent glioblastoma incidence trend in the United States. This study aims to provide in-depth description of the patterns of incidence trends and to examine the age-period-cohort effects to the trends of glioblastoma specific to elderly patients.

Methods
The incidence rates were age-adjusted and reported per 100,000 population. We calculated the annual percent change (APC) in incidence using the Joinpoint Regression Program and conducted an age-period-cohort analysis of elderly glioblastoma reported between 2000 and 2017 to the Surveillance Epidemiology and End Results (SEER) 18 registry database.

Results
The overall incidence rate of elderly patients with glioblastoma was 13.16 per 100,000 (95% CI, 12.99–13.32) from 2000 to 2017. Non-Hispanic whites (20,406, 83.6%) made up the majority. The incidence rate of male was about 1.62 times that of female. The trend of incidence remained stable and there was a non-significant increasing tendency for all elderly patients (APC 0.3, 95% CI, − 0.1 to 0.7, p = 0.111). There was a significantly increasing incidence trend for non-Hispanic white (APC 0.6, 95% CI, 0.2 to 1.1, p = 0.013), supratentorial location (APC 0.7, 95% CI, 0.2 to 1.3, p = 0.016), tumor size < 4 cm (APC 2.5, 95% CI, 1.4 to 3.6, p < 0.001), and a significantly decreasing trend for overlapping/NOS location (APC -0.9, 95% CI, − 1.6 to − 0.2, p = 0.012), and unknown tumor size (APC -4.9, 95% CI, − 6.6 to − 3.3, p < 0.001). The age-period-cohort analysis showed the effect of age on incidence trends (p< 0.001, Wald test), while did not indicate the period and cohort effects of the incidence trends of glioblastoma (p = 0.063 and p =0.536, respectively, Wald test).

Conclusion
The overall incidence of glioblastoma in the elderly population remained stable between 2000 and 2017. Period and cohort effects were not evident in the trend of glioblastoma incidence. Future population-based studies exploring the difference in the trend of glioblastoma incidence by specific molecular subgroups are warranted to further our understanding of the etiology of glioblastoma.
Sub-optimal gain in vision in retinal vein occlusion due to under-treatment in the real world: results from an open-label prospective study of Intravitreal Ranibizumab
Authors: Narayanan Raja , Kelkar Aditya , Abbas Zahir , Goel Neha , Soman Manoj , Naik Naveen , Sudhalkar Aditya , Walinjkar Jaydeep , Shah Utkarsh , Maksane Nitin 
Published: January 2021

Abstract
Background
Macular edema secondary to retinal vein occlusion (RVO) is an important cause of loss of vision. Intravitreal injections (IVI) of anti-vascular endothelial growth factor (VEGF) are the standard of care in this disease, as shown in numerous randomized controlled trials. The purpose of this study was to study the efficacy and safety of ranibizumab, an anti-VEGF agent, in the real-world setting.

Methods
This was 48 weeks, open-label, prospective, multicentre, observational study. Patients diagnosed with ME secondary to RVO were treated with IVI of Ranibizumab 0.5 mg in real-world conditions. Efficacy was measured by improvement seen in best-corrected visual acuity (BCVA) in terms of Early Treatment of Diabetic Retinopathy Study (ETDRS) Letter Scores and change in central retinal thickness (CRT) measured by optical coherence tomography.

Results
One hundred eyes of 100 patients (79 with branch retinal vein occlusion and 21 with central retinal vein occlusion) were recruited in the study. The mean (standard deviation, SD) BCVA was 52.8 (21.99) letters at baseline and 62.3 (24.40) letters at week 48. From baseline, there was a significant improvement in BCVA by 7.7 letters (p = 0.001) at 48 weeks. The mean (SD) of CRT was 479.9 (216.25) μm at baseline and it decreased significantly to 284.9 (171.35) μm at week 48 (p < 0.001). During the study period, the average number of intravitreal injections was 3.5 per patient. There was no report of endophthalmitis in any eye.

Conclusions
Ranibizumab is well tolerated and effective in treating macular edema secondary to RVO in real-world clinical settings. However, there is under-treatment compared to controlled clinical trials, and the gain in vision is sub-optimal with under-treatment.

Trial registration
Clinical Trials Registry - India: CTRI/2015/07/005985.
A comparison of optic disc area measured by confocal scanning laser tomography versus Bruch’s membrane opening area measured using optical coherence tomography
Authors: Cazana Ioana Maria , Böhringer Daniel , Reinhard Thomas , Evers Charlotte , Engesser Diana , Anton Alexandra , Lübke Jan 
Published: January 2021

Abstract
Background
Precise optic disc size measurements based on anatomically exact disc margins are fundamental for a correct assessment of glaucoma suspects. Computerized imaging techniques, such as confocal-scanning-laser-tomography (CSLT), which applies operator defined boundaries and optical-coherence-tomography (OCT), which incorporates an alternative detectable landmark (Bruch’s-membrane-opening (BMO)), have simplified the planimetry of the optic disc and BMO-area, respectively. This study’s objectives are to compare both modalities for area and to define a threshold for macro-BMO using BMO-OCT.

Methods
Retrospectively, patients that simultaneously received CSLT and BMO-OCT scans were included. Their images were correlated and agreement was determined using Bland-Altman-analysis. The diagnostic power of a macro-BMO threshold using OCT was derived after creating a receiver-operating-characteristics-curve using the well-established analogous CSLT threshold (2.43 mm2).

Results
Our study included 373 eyes with a median optic disc area by CSLT/ BMO-area by OCT of 2.56 mm2 and 2.19 mm2 respectively. The Bland-Altman-analysis revealed a systematic deviation with a diverging tendency with increasing area, which enabled the creation of the following mathematical relation: disc-area (CSLT)*0.73 + 0.3 = BMO-area (OCT). BMO-area of 2.19 mm2 showed the best diagnostic power for identifying macro-BMOs using OCT (sensitivity: 75%, specificity: 86%).

Conclusions
Area measurements (CSLT optic disc area vs. BMO-area by OCT) showed a systematic deviation with a divergent tendency with increasing size. Our mathematical equation offers an estimated comparison of these anatomically diverse entities. Considering BMO-OCT´ anatomical accuracy, the 2.19 mm2 threshold may improve discernment between glaucoma suspects and norm variants.
Correlates of uptake of HIV testing among children and young adolescents in Akwa-Ibom state, Nigeria: a secondary data analysis of the Akwa-Ibom aids indicator survey, 2017
Authors: Adetoro Damilola , Khamofu Hadiza , Badru Titilope , Markson John , Adedokun Oluwasanmi , Sandah-Abubakar Nana , Dafa Ibrahim , Chen Mario , Chiegil Robert , Torpey Kwasi 
Published: January 2021

Abstract
Background
In order to end the AIDS epidemic by 2030, there is a need to significantly reduce the rate of new infection among children and young adolescents. Identifying the correlates of testing behaviour is necessary to improve HIV testing campaigns by refining messages that target individuals in this age group. The objective of this study was to determine the correlates of HIV testing among children and young adolescents in Akwa-Ibom, Nigeria.

Methods
The outcome was a secondary data analysis of the 2017 Akwa-Ibom AIDS Indicator Survey. Data of 4037 children and young adolescents aged 0–14 years was assessed in this study. Analysis was done using STATA version 16. Chi-squared test and logistic regression models were used to measure association and its strength between uptake of HIV testing and some independent variables (child/caregiver’s age, sex, educational status, child’s location, caregiver’s knowledge of HIV and caregiver ever tested for HIV) at 5% significance level.

Results
Result showed that only 14.2% of the children and young adolescents have been tested for HIV. Previous history of blood transfusion (AOR = 5.33, 95%C.I = 2.60–10.92, P = < 0.001), caregiver’s level of education (AOR = 2.67, 95%C.I = 1.30–5.51, P = 0.008) and caregiver ever tested for HIV (AOR = 8.31, 95%C.I = 5.67–12.19, P = < 0.001) were significantly associated with uptake of HIV testing.

Conclusion
This study concludes that a large proportion of children and young adolescents in Akwa-Ibom state have never been tested for HIV. There is a need for HIV testing interventions to be targeted towards this age groups and their parents/guardian. Addressing the knowledge gap amongst caregivers especially in rural areas is crucial towards improving the effectiveness of HIV testing interventions.
Serum lithium test requesting across three UK regions: an evaluation of adherence to monitoring guidelines
Authors: Parfitt Ceri , Duff Christopher J. , Scargill Jonathan , Green Lewis , Holland David , Heald Adrian H. , Fryer Anthony A. 
Published: January 2021

Abstract
Background
Bipolar disorder is the fourth most common mental health condition, affecting ~ 1% of UK adults. Lithium is an effective treatment for prevention of relapse and hospital admission, and is widely recommended as a first-line treatment. We previously showed in other areas that laboratory testing patterns are variable with sub-optimal conformity to guidance. We therefore examined lithium results and requesting patterns relative to monitoring recommendations.

Methods
Data on serum lithium levels and intervals between requests were extracted from Clinical Biochemistry laboratory information systems at the University Hospitals of North Midlands, Salford Royal Foundation Trust and Pennine Acute Hospitals from 2012 to 2018 (46,555 requests; 3371 individuals). Data were examined with respect to region/source of request, age and sex.

Results
Across all sites, lithium levels on many requests were outside the recommended UK therapeutic range (0.4–0.99 mmol/L); 19.2% below the range and 6.1% above the range (median [Li]: 0.60 mmol/L). A small percentage were found at the extremes (3.2% at < 0.1 mmol/L, 1.0% at ≥1.4 mmol/L). Most requests were from general practice (56.3%) or mental health units (34.4%), though those in the toxic range (≥1.4 mmol/L) were more likely to be from secondary care (63.9%). For requesting intervals, there was a distinct peak at 12 weeks, consistent with guidance for those stabilised on lithium therapy. There was no peak at 6 months, as recommended for those aged < 65 years on unchanging therapy, though re-test intervals in this age group were more likely to be longer. There was a peak at 0–7 days, reflecting those requiring closer monitoring (e.g. treatment initiation, toxicity). However, for those with initial lithium concentrations within the BNF range (0.4–0.99 mmol/L), 69.4% of tests were requested outside expected testing frequencies.

Conclusions
Our data showed: (a) lithium levels are often maintained at the lower end of the recommended therapeutic range, (b) patterns of lithium results and testing frequency were comparable across three UK sites with differing models of care and, (c) re-test intervals demonstrate a noticeable peak at the recommended 3-monthly, but not at 6-monthly intervals. Many tests were repeated outside expected frequencies, indicating the need for measures to minimise inappropriate testing.
A digital lifestyle behaviour change intervention for the prevention of type 2 diabetes: a qualitative study exploring intuitive engagement with real-time glucose and physical activity feedback
Authors: Whelan Maxine E. , Denton Francesca , Bourne Claire L. A. , Kingsnorth Andrew P. , Sherar Lauren B. , Orme Mark W. , Esliger Dale W. 
Published: January 2021

Abstract
Background
Mobile health technologies have advanced to now allow monitoring of the acute physiological responses to lifestyle behaviours. Our aim was to explore how people engaged with real-time feedback on their physical activity and glucose levels over several weeks.

Methods
Semi-structured interviews with 26 participants (61.5% female, 56.6 years) at moderate-to-high risk of developing type 2 diabetes were conducted. Interviews were completed after participants took part in an intervention comprising a flash glucose monitor (Freestyle Libre) and a physical activity monitor (Fitbit Charge 2). Purposive sampling ensured representation of ages, genders and group allocations.

Results
Inductive thematic analysis revealed how individuals intuitively used, interpreted and acted on feedback from wearable technologies. Six key themes emerged: triggers of engagement with the technologies, links between behaviour and health, lack of confidence, changes to movement behaviours, changes to diet and barriers to lifestyle behaviour change.

Conclusions
Our findings demonstrate that accessing behavioural and physiological feedback can increase self-awareness of how lifestyle impacts short-term health. Some participants noticed a link between the feedback presented by the two devices and changed their behaviour but many did not. Training and educational support, as well as efforts to optimize how feedback is presented to users, are needed to sustain engagement and behaviour change. Extensions of this work to involve people with diabetes are also warranted to explore whether behavioural and physiological feedback in parallel can encourage better diabetes self-management.

Trial registration
ISRCTN Registry, ISRCTN17545949, 12/05/2017, prospectively registered.
Simulating preventative testing of SARS-CoV-2 in schools: policy implications
Authors: Asgary Ali , Cojocaru Monica Gabriela , Najafabadi Mahdi M. , Wu Jianhong 
Published: January 2021

Abstract
Background
School testing for SARS-CoV-2 infection has become an important policy and planning issue as schools were reopened after the summer season and as the COVID-19 pandemic continues. Decisions to test or not to test and, if testing, how many tests, how often and for how long, are complex decisions that need to be taken under uncertainty and conflicting pressures from various stakeholders.

Method
We have developed an agent-based model and simulation tool that can be used to analyze the outcomes and effectiveness of different testing strategies and scenarios in schools with various number of classrooms and class sizes. We have applied a modified version of a standard SEIR disease transmission model that includes symptomatic and asymptomatic infectious populations, and that incorporates feasible public health measures. We also incorporated a pre-symptomatic phase for symptomatic cases. Every day, a random number of students in each class are tested. If they tested positive, they are placed in self-isolation at home when the test results are provided. Last but not least, we have included options to allow for full testing or complete self-isolation of a classroom with a positive case.

Results
We present sample simulation results for parameter values based on schools and disease related information, in the Province of Ontario, Canada. The findings show that testing can be an effective method in controlling the SARS-CoV-2 infection in schools if taken frequently, with expedited test results and self-isolation of infected students at home.

Conclusions
Our findings show that while testing cannot eliminate the risk and has its own challenges, it can significantly control outbreaks when combined with other measures, such as masks and other protective measures.
Pulmonary cavitation: an under-recognized late complication of severe COVID-19 lung disease
Authors: Zoumot Zaid , Bonilla Maria-Fernanda , Wahla Ali S. , Shafiq Irfan , Uzbeck Mateen , El-Lababidi Rania M. , Hamed Fadi , Abuzakouk Mohamed , ElKaissi Mahmoud 
Published: January 2021

Abstract
Background
Pulmonary radiological findings of the novel coronavirus disease 2019 (COVID-19) have been well documented and range from scattered ground-glass infiltrates in milder cases to confluent ground-glass change, dense consolidation, and crazy paving in the critically ill. However, lung cavitation has not been commonly described in these patients. The objective of this study was to assess the incidence of pulmonary cavitation in patients with COVID-19 and describe its characteristics and evolution.

Methods
We conducted a retrospective review of all patients admitted to our institution with COVID-19 and reviewed electronic medical records and imaging to identify patients who developed pulmonary cavitation.

Results
Twelve out of 689 (1.7%) patients admitted to our institution with COVID-19 developed pulmonary cavitation, comprising 3.3% (n = 12/359) of patients who developed COVID-19 pneumonia, and 11% (n = 12/110) of those admitted to the intensive care unit. We describe the imaging characteristics of the cavitation and present the clinical, pharmacological, laboratory, and microbiological parameters for these patients. In this cohort six patients have died, and six discharged home.

Conclusion
Cavitary lung disease in patients with severe COVID-19 disease is not uncommon, and is associated with a high level of morbidity and mortality.