bluuebunny/crossref_metadata_2025_split huggingface dataset:
Borrowing information across patient subgroups in clinical trials, with application to a paediatric trial
Authors: Turner Rebecca M. , Turkova Anna , Moore Cecilia L. , Bamford Alasdair , Archary Moherndran , Barlow-Mosha Linda N. , Cotton Mark F. , Cressey Tim R. , Kaudha Elizabeth , Lugemwa Abbas , Lyall Hermione , Mujuru Hilda A. , Mulenga Veronica , Musiime Victor , Rojo Pablo , Tudor-Williams Gareth , Welch Steven B. , Gibb Diana M. , Ford Deborah , White Ian R. ,   and the ODYSSEY Trial Team
Published: February 2022

Abstract
Background
Clinical trial investigators may need to evaluate treatment effects in a specific subgroup (or subgroups) of participants in addition to reporting results of the entire study population. Such subgroups lack power to detect a treatment effect, but there may be strong justification for borrowing information from a larger patient group within the same trial, while allowing for differences between populations. Our aim was to develop methods for eliciting expert opinions about differences in treatment effect between patient populations, and to incorporate these opinions into a Bayesian analysis.

Methods
We used an interaction parameter to model the relationship between underlying treatment effects in two subgroups. Elicitation was used to obtain clinical opinions on the likely values of the interaction parameter, since this parameter is poorly informed by the data. Feedback was provided to experts to communicate how uncertainty about the interaction parameter corresponds with relative weights allocated to subgroups in the Bayesian analysis. The impact on the planned analysis was then determined.

Results
The methods were applied to an ongoing non-inferiority trial designed to compare antiretroviral therapy regimens in 707 children living with HIV and weighing ≥ 14 kg, with an additional group of 85 younger children weighing < 14 kg in whom the treatment effect will be estimated separately. Expert clinical opinion was elicited and demonstrated that substantial borrowing is supported. Clinical experts chose on average to allocate a relative weight of 78% (reduced from 90% based on sample size) to data from children weighing ≥ 14 kg in a Bayesian analysis of the children weighing < 14 kg. The total effective sample size in the Bayesian analysis was 386 children, providing 84% predictive power to exclude a difference of more than 10% between arms, whereas the 85 younger children weighing < 14 kg provided only 20% power in a standalone frequentist analysis.

Conclusions
Borrowing information from a larger subgroup or subgroups can facilitate estimation of treatment effects in small subgroups within a clinical trial, leading to improved power and precision. Informative prior distributions for interaction parameters are required to inform the degree of borrowing and can be informed by expert opinion. We demonstrated accessible methods for obtaining opinions.
Objective disease activity assessment and therapeutic drug monitoring prior to biologic therapy changes in routine inflammatory bowel disease clinical practice: TARGET-IBD
Authors: Click Benjamin , Barnes Edward L. , Cohen Benjamin L. , Sands Bruce E. , Hanson John S. , Rubin David T. , Dubinsky Marla C. , Regueiro Miguel , Gazis Derek , Crawford Julie M. , Long Millie D. 
Published: February 2022

Abstract
Background
Inflammatory bowel disease (IBD) treatment paradigms recommend objective disease activity assessment and reactive therapeutic drug monitoring (TDM) prior to changes in biologic therapy. We aimed to describe objective marker and TDM assessment in routine clinical practice prior to biologic therapeutic changes in adult IBD patients.

Methods
TARGET-IBD is a prospective longitudinal cohort of over 2100 IBD patients receiving usual care at 34 US academic or community centers enrolled between June 2017 and October 2019 who received biologic therapy and had a dose change or biologic discontinuation for lack of efficacy. Objective markers of disease activity within 12 weeks prior included fecal calprotectin, C-reactive protein (CRP), endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI). TDM data for infliximab or adalimumab was obtained.

Results
525 patients (71.4% Crohn’s disease [CD], 28.6% ulcerative colitis [UC]) receiving biologic therapy underwent dose change (55.6%) or discontinuation (44.4%) for lack of efficacy. The majority were Caucasian (85.7%), 18–39 years old (52.2%), privately insured (81.5%), and at academic centers (73.7%). For dose changes, 67.5% had at least one objective disease activity assessment or TDM in the 12 weeks prior (CD 67.9%, UC 66.2%; P = 0.79). The most common objective marker was CRP in both CD (39.1%) and UC (54.5%). CRP and calprotectin were used significantly more in UC (P = 0.02 and P = 0.03). TDM was obtained in 30.7% (28.8% UC, 31.4% CD; P = 0.72) prior to dose change. For biologic discontinuation, 79.4% patients underwent objective assessment or TDM prior. In CD, CRP (46.3%) was most common, and CT (P = 0.03) and MRI (P < 0.001) were significantly more frequent than in UC. TDM was performed in 40.1% of patients (43.5% UC, 38.0% CD, P = 0.49) prior to discontinuation. Among all participants with dose change or discontinuation, endoscopy was performed in 29.3% with CD and 31.3% with UC. Academic care setting was associated with objective assessment before therapy change (OR 1.59, 95% CI 1.01–2.50).

Conclusion
Nearly one-third of patients undergoing a biologic dose change or discontinuation do not undergo objective disease activity assessment or TDM. Assessment choice differs by disease. Future studies assessing the impact of such practices on long-term outcomes are needed.
Excess fatty acids induce pancreatic acinar cell pyroptosis through macrophage M1 polarization
Authors: Xia Wenwen , Lu Zhaomin , Chen Wei , Zhou Jianjun , Zhao Yan 
Published: February 2022

AbstractFree fatty acid derived from hyperlipidemia contributes to the development of inflammation in the pancreas. Here we explore the molecular mechanisms of fatty acid-induced pancreatitis through cellular experiments and the construction of a mouse model of hyperlipidemic pancreatitis. We found that palmitic acid stimulation leads to M1 polarization of macrophage, which secretes cathepsin S via exosomes to pancreatic acinar cells and leads to activation of the caspase1-mediated classical pyrolysis pathway, resulting in inflammation and pancreatic tissue damage. In vivo experiments have also demonstrated that the high levels of fatty acids induced by hyperlipidaemia exacerbate the development of pancreatitis, and that cathepsin S inhibitors significantly alleviate hyperlipidemic pancreatitis. Therefore, cathepsin S may be a new target for the clinical treatment of hyperlipidemic pancreatitis.
Distal radius fractures in the superelderly: an observational study of 8486 cases from the Swedish fracture register
Authors: Sagerfors Marcus , Jakobsson Hugo , Thórdardóttir Ásgerdur , Wretenberg Per , Möller Michael 
Published: February 2022

Abstract
Background
The distal radius fracture (DRF) is the most common fracture in adults. With an ageing population, the number of wrist fractures in the superelderly (≥ 80 years) is expected to rise. Optimal treatment for displaced DRFs remains controversial, especially in the superelderly group. In addition, basic knowledge of the outcome after a DRF in this heterogenic group is lacking. The aim of this study was to study injury characteristics, treatment and outcome of DRFs in superelderly patients using data from a large national register.

Methods
We used prospectively collected data from the Swedish Fracture Register. All distal radius fractures registered between April 2012 and December 2018 in patients ≥ 80 years of age were included. Data on epidemiology, fracture type, trauma mechanism and treatment are registered by the physician treating the patient. Patients are also sent a subjective outcome questionnaire including EQ-5D, EQ-VAS and Short Musculoskeletal Function Assessment questionnaire (SMFA-score) at the time of injury and after 12 months. The 12-month questionnaire was sent to those who had completed the questionnaire at the time of injury. A Mann–Whitney U-test was used to assess differences between treatment methods.

Results
Mean age for this population was 86 years (80–105 years), a majority of the patients were female (86.7%). The dominating injury mechanism was a simple fall (74.6%) in the patient’s residence. The majority of fractures were AO type A (70%) followed by AO type C (20.9%) and type B (8.6%). The incidence of open fractures was significantly higher in females (2.6%) compared to males (1.5%). A majority of the fractures were treated with a cast (87.5%) with volar locking plate as the second most common treatment method (6.6%). Patient-reported outcome measures (PROMs) EQ-5D, EQ-VAS and the Arm Hand Function Index of the SMFA-score deteriorated somewhat one year after injury compared to pre-injury. PROMs did not correlate to treatment with cast or a volar plate.

Conclusions
This nationwide register study provides detailed data on DRFs in the superelderly regarding epidemiology, treatment and self-reported outcome. A good self-reported outcome is possible, but many patients do not recover completely. PROMs did not correlate to type of treatment. The frequency of open fractures was significantly higher in females. The reason for this is unclear but different skin thickness in older males versus females may be one explanation.
Is Frailty Index a better predictor than pre-stroke modified Rankin Scale for neurocognitive outcomes 3-months post-stroke?
Authors: Munthe-Kaas Ragnhild , Aam Stina , Saltvedt Ingvild , Wyller Torgeir Bruun , Pendlebury Sarah T. , Lydersen Stian , Hagberg Guri , Schellhorn Till , Rostoft Siri , Ihle-Hansen Hege 
Published: February 2022

AbstractBackgroundThe prognostic value of frailty measures for post-stroke neurocognitive disorder (NCD) remains to be evaluated.AimsThe aim of this study was to compare the predictive value of pre-stroke FI with pre-stroke modified Rankin Scale (mRS) for post-stroke cognitive impairment. Further, we explored the added value of including FI in prediction models for cognitive prognosis post-stroke.MethodsWe generated a 36-item Frailty Index (FI), based on the Rockwood FI, to measure frailty based on pre-stroke medical conditions recorded in the Nor-COAST multicentre prospective study baseline assessments. Consecutive participants with a FI score and completed cognitive test battery at three months were included. We generated Odds Ratio (OR) with NCD as the dependent variable. The predictors of primary interest were pre-stroke frailty and mRS. We also measured the predictive values of mRS and FI by the area (AUC) under the receiver operating characteristic curve.Results598 participants (43.0% women, mean/SD age = 71.6/11.9, mean/SD education = 12.5/3.8, mean/SD pre-stroke mRS = 0.8/1.0, mean/SD GDS pre-stroke = 1.4/0.8, mean/SD NIHSS day 1 3/4), had a FI mean/SD score = 0.14/0.10. The logistic regression analyses showed that FI (OR 3.09), as well as the mRS (OR 2.21), were strong predictors of major NCD. When FI and mRS were entered as predictors simultaneously, the OR for mRS decreased relatively more than that for FI. AUC for NCD post-stroke was higher for FI than for mRS, both for major NCD (0.762 vs 0.677) and for any NCD (0.681 vs 0.638).ConclusionsFI is a stronger predictor of post-stroke NCD than pre-stroke mRS and could be a part of the prediction models for cognitive prognosis post-stroke.Trial RegistrationClinicalTrials.gov Identifier:NCT02650531.
Dynamic changes of viral load and the duration of viral shedding in patients with hand, foot and mouth disease: a protocol for longitudinal study
Authors: Duan Xiaoxia , Zhang Chaoyong , Chen Zhenhua , Liao Juan , Zeng Yilan , Huang Weiwei , Ren Xueling , Tang Xueqin , Peng Hongxia , Zhang Delan , Wang Xiao , Yuan Ping , Long Lu 
Published: February 2022

Abstract
Background
The duration of virus shedding is necessary for determining the infectious period. But there were few quantitative studies on the changes of viral load and the law of the viral shedding in hand foot and mouth disease (HFMD) patients has not yet been clarified.

Methods
This study will prospectively recruit coxsackievirus A10 (CV-A10), coxsackievirus A16 (CV-A16) and coxsackievirus A6 (CV-A6) infected inpatients from January 2022 to December 2022. A series of samples and questionnaire information will be collected regularly to establish the dynamic function relationship between time and viral load changes and a Bayesian multilevel model will be constructed to clarify the evolvement rules which reflect the dynamic changes of viral load and the duration of viral shedding in patients with HFMD.

Discussion
The results of this study is expected to further clarify the evolvement rules which reflect the dynamic changes of viral load and the duration of viral shedding in HFMD patients under the influence of related factors. It can also provide important evidence for the scientific definition of the infectious period and isolation period of HFMD in China.
A new tool for assessing Pectus Excavatum by a semi-automatic image processing pipeline calculating the classical severity indexes and a new marker: the Volumetric Correction Index
Authors: Trò Rosella , Martini Simona , Stagnaro Nicola , Sambuceti Virginia , Torre Michele , Fato Marco Massimo 
Published: February 2022

Abstract
Background
In clinical assessment of Pectus Excavatum (PE), the indication to surgery is based not only on symptoms but also on quantitative markers calculated from Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scans. According to clinical routine, these indexes are measured manually by radiologists with limited computer support. This process is time consuming and potentially subjected to inaccuracy and individual variability in measurements. Moreover, the existing indexes have limitations, since they are based on linear measurements performed on single slices rather than on volumetric data derived from all the thoracic scans.

Results
In this paper we present an image processing pipeline aimed at providing radiologists with a computer-aid tool in support of diagnosis of PE patients developed in MATLAB® and conceived for MRI images. This framework has a dual purpose: (i) to automatize computation of clinical indexes with a view to ease and standardize pre-operative evaluation; (ii) to propose a new marker of pathological severity based on volumetric analysis and overcoming the limitations of existing axial slice-based indexes. Final designed framework is semi-automatic, requiring some user interventions at crucial steps: this is realized through a Graphical User Interface (GUI) that simplifies the interaction between the user and the tools. We tested our pipeline on 50 pediatric patients from Gaslini Children’s Hospital and performed manual computation of indexes, comparing the results between the proposed tool and gold-standard clinical practice. Automatic indexes provided by our algorithm have shown good agreement with manual measurements by two independent readers. Moreover, the new proposed Volumetric Correction Index (VCI) has exhibited good correlation with standardized markers of pathological severity, proving to be a potential innovative tool for diagnosis, treatment, and follow-up.

Conclusions
Our pipeline represents an innovative image processing in PE evaluation, based on MRI images (radiation-free) and providing the clinician with a quick and accurate tool for automatically calculating the classical PE severity indexes and a new more comprehensive marker: the Volumetric Correction Index.
Severe maternal hardships are associated with food insecurity among low-income/lower-income women during pregnancy: results from the 2012–2014 California maternal infant health assessment
Authors: Laraia Barbara A. , Gamba Ryan , Saraiva Carina , Dove Melanie S. , Marchi Kristen , Braveman Paula 
Published: February 2022

Abstract
Background
Assess the associations between ten severe maternal hardships and food insecurity experienced during pregnancy.

Methods
Data on 14,274 low-income/lower-income women (below 400% of the income to federal poverty guideline ratio) from the statewide-representative 2010–2012 California Maternal and Infant Health Assessment were used to estimate food security status prevalence. Prevalence of severe maternal hardships by food security status was estimated. Multinomial logistic regression was used to assess the associations between severe maternal hardship and food security status, adjusting for sociodemographic characteristics.

Results
Food insecurity was common among low- and lower-income pregnant women in California; 23.4% food insecure and an additional 11.5% marginally secure. In adjusted analysis, nine of ten hardships were associated with food security status. Only the respondent or someone close to the respondent having a problem with alcohol or drugs was not associated with food security status after adjusting for socioeconomic factors. Husband/partner losing a job, depressive symptoms, not having practical support and intimate partner violence were consistently associated with marginal, low and very low food security status. Each additional severe maternal hardship a woman experienced during pregnancy was associated with a 36% greater risk of reporting marginal food security (Relative Risk Ratio 1.36, 95% CI: 1.27, 1.47), 54% for low food security (Relative Risk Ratio 1.54, 95% CI: 1.44, 1.64), and 99% for very low food security (Relative Risk Ratio 1.99, 95% CI: 1.83, 2.15).

Conclusions
Food security status was strongly linked with several maternal hardships that could jeopardize maternal and/or infant health.
Services—including prenatal care and nutritional assistance—for a large proportion of pregnant women should address a wide range of serious unmet social needs including food insecurity.
Examining the effects of second-and third-trimester gestational weight gain rates on the perinatal outcomes among Chinese twin pregnancies: a retrospective cohort study
Authors: Lin Li-hua , Weng Yi-lin , Lin Ying-ying , Huang Xiu-xian , Lin Yang , Xiu Xiao yan , Yan Jian-ying , Lin Juan 
Published: February 2022

Abstract
Background
This paper investigated how second- and third-trimester gestational weight gain relates to perinatal outcomes among normal weight women with twin pregnancies in Fujian, China.

Methods
A retrospective study examining the medical records of 931 normal weight twin-pregnant women was conducted in Fujian Maternity and Child Health Hospital from 2014 to 2018.The 2nd and 3rdtrimester weekly weight gain rates were calculated, and women were categorized as gaining below, within, or above the 2009 Institute of Medicine (IOM) recommended rates. The association between the trimester-specific weight gain rate and perinatal outcome was determined by traditional regression analysis among groups.

Results
A total of 25.9%, 19.8% and 54.3% of women had rates of weight gain across the 2nd and 3rd trimesters less than, greater than or within the recommended rates respectively. Multivariate logistic regression analysis showed that weight gain greater than the recommended rate in the 2nd trimester was associated with a decreased risk of preeclampsia (aOR:0.489,95%CI:0.289 ~ 0.974). Weight gain less than the recommended rate of weight gain in the 3rd trimester was associated with increased risks of premature delivery(aOR:2.079, 95%CI:1.467 ~ 2.968), gestational diabetes mellitus (aOR: 2.048, 95%CI:1.411 ~ 2.971), intrahepatic cholestasis syndrome (aOR:3.015,95%CI: 1.058 ~ 8.587), pre-labour rupture of membrane (aOR: 1.708,95%CI: 1.169 ~ 2.493), average twin birth weight < 2500 g(aOR:1.532,95%CI: 1.125 ~ 2.084) and neonatal respiratory distress syndrome (aOR:4.934,95%CI:1.626 ~ 15.083) and was associated with decreased risks of caesarean section (aOR:0.589,95%CI:0.386 ~ 0.898) and preeclampsia (aOR:0.471, 95%CI:0.274 ~ 0.808). In addition, weight gain greater than the recommended rate of weight gain in the 3rd trimester was associated with increased risks of premature delivery (aOR:1.589,95%CI:1.428 ~ 2.951) and gestational hypertension (aOR:2.137,95% CI:1.034 ~ 4.415) as well as preeclampsia (aOR:2.246, 95%CI:1.462 ~ 3.452). The stratified analysis of weight gain in the 3rd trimester showed that there was no significant difference in the incidence of adverse pregnancy outcomes compared to the 2nd trimester weight gain groups.

Conclusions
While this study showed that a gestational weight gain rate above or below the recommendation in the 3rd trimester was associated with some adverse maternal and neonatal outcomes, further prospective and multicentre studies are required to explore alternate ranges of gestational weight gain rates in twin pregnancies.
A foresight whole systems obesity classification for the English UK biobank cohort
Authors: Clark Stephen , Lomax Nik , Birkin Mark , Morris Michelle 
Published: February 2022

Abstract
Background
The number of people living with obesity or who are overweight presents a global challenge, and the development of effective interventions is hampered by a lack of research which takes a joined up, whole system, approach that considers multiple elements of the complex obesity system together. We need to better understand the collective characteristics and behaviours of those who are overweight or have obesity and how these differ from those who maintain a healthy weight.

Methods
Using the UK Biobank cohort we develop an obesity classification system using k-means clustering. Variable selection from the UK Biobank cohort is informed by the Foresight obesity system map across key domains (Societal Influences, Individual Psychology, Individual Physiology, Individual Physical Activity, Physical Activity Environment).

Results
Our classification identifies eight groups of people, similar in respect to their exposure to known drivers of obesity: ‘Younger, urban hard-pressed’, ‘Comfortable, fit families’, ‘Healthy, active and retirees’, ‘Content, rural and retirees’, ‘Comfortable professionals’, ‘Stressed and not in work’, ‘Deprived with less healthy lifestyles’ and ‘Active manual workers’. Pen portraits are developed to describe the characteristics of these different groups. Multinomial logistic regression is used to demonstrate that the classification can effectively detect groups of individuals more likely to be living with overweight or obesity. The group identified as ‘Comfortable, fit families’ are observed to have a higher proportion of healthy weight, while three groups have increased relative risk of being overweight or having obesity: ‘Active manual workers’, ‘Stressed and not in work’ and ‘Deprived with less healthy lifestyles’.

Conclusions
This paper presents the first study of UK Biobank participants to adopt this obesity system approach to characterising participants. It provides an innovative new approach to better understand the complex drivers of obesity which has the potential to produce meaningful tools for policy makers to better target interventions across the whole system to reduce overweight and obesity.