bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in the clinical characteristics and outcomes of COVID-19 patients in the epicenter and peripheral areas of the pandemic from China: a retrospective, large-sample, comparative analysis
Authors:   on behalf of the Sichuan & Wuhan Collaboration Research Group, and Sichuan Treatment Expert Group for COVID-19, China, Wang Gang , Luo Feng Ming , Liu Dan , Liu Jia Sheng , Wang Ye , Chen Hong , Tian Pan Wen , Fan Tao , Tang Li , Yu He , Wang Lan , Feng Mei , Ni Zhong , Wang Bo , Song Zhi Fang , Wu Xiao Ling , Wang Hong Jun , Tong Xiang , Xue Miao , Lei Xian Ying , Long Bo , Jia Chao , Xiao Jun , Shang Juan , Xiong Nian , Luo Jian Fei , Liang Zong An , Li Wei Min 
Published: February 2021

AbstractBackgroundThere is limited information on the difference in epidemiology, clinical characteristics and outcomes of the initial outbreak of the coronavirus disease (COVID-19) in Wuhan (the epicenter) and Sichuan (the peripheral area) in the early phase of the COVID-19 pandemic. This study was conducted to investigate the differences in the epidemiological and clinical characteristics of patients with COVID-19 between the epicenter and peripheral areas of pandemic and thereby generate information that would be potentially helpful in formulating clinical practice recommendations to tackle the COVID-19 pandemic.MethodsThe Sichuan & Wuhan Collaboration Research Group for COVID-19 established two retrospective cohorts that separately reflect the epicenter and peripheral area during the early pandemic. The epidemiology, clinical characteristics and outcomes of patients in the two groups were compared. Multivariate regression analyses were used to estimate the adjusted odds ratios (aOR) with regard to the outcomes.ResultsThe Wuhan (epicenter) cohort included 710 randomly selected patients, and the peripheral (Sichuan) cohort included 474 consecutive patients. A higher proportion of patients from the periphery had upper airway symptoms, whereas a lower proportion of patients in the epicenter had lower airway symptoms and comorbidities. Patients in the epicenter had a higher risk of death (aOR=7.64), intensive care unit (ICU) admission (aOR=1.66), delayed time from illness onset to hospital and ICU admission (aOR=6.29 and aOR=8.03, respectively), and prolonged duration of viral shedding (aOR=1.64).ConclusionsThe worse outcomes in the epicenter could be explained by the prolonged time from illness onset to hospital and ICU admission. This could potentially have been associated with elevated systemic inflammation secondary to organ dysfunction and prolonged duration of virus shedding independent of age and comorbidities. Thus, early supportive care could achieve better clinical outcomes.
Drug susceptibility patterns of Mycobacterium tuberculosis from adults with multidrug-resistant tuberculosis and implications for a household contact preventive therapy trial
Authors:   for the ACTG A5300/IMPAACT I2003 PHOENIx Feasibility study team, Demers Anne-Marie , Kim Soyeon , McCallum Sara , Eisenach Kathleen , Hughes Michael , Naini Linda , Mendoza-Ticona Alberto , Pradhan Neeta , Narunsky Kim , Poongulali Selvamuthu , Badal-Faesen Sharlaa , Upton Caryn , Smith Elizabeth , Shah N. Sarita , Churchyard Gavin , Gupta Amita , Hesseling Anneke , Swindells Susan 
Published: February 2021

Abstract
Background
Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs).

Methods
As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability.

Results
Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens.

Conclusions
RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.
Chronic kidney disease, atherosclerotic plaque characteristics on carotid magnetic resonance imaging, and cardiovascular outcomes
Authors: Beddhu Srinivasan , Boucher Robert E. , Sun Jie , Balu Niranjan , Chonchol Michel , Navaneethan Sankar , Chertow Glenn M. , Townsend Raymond , Haley William , Cheung Alfred K. , Conroy Molly B. , Raj Dominic S. , Xu Dongxiang , George Thomas , Yunis Reem , Wei Guo , Canton Gador , Bates Jeffrey , Chen Jing , Papademetriou Vasilios , Punzi Henry , Wiggers Alan , Wright Jackson T. , Greene Tom , Yuan Chun 
Published: February 2021

Abstract
Background
It is unclear whether faster progression of atherosclerosis explains the higher risk of cardiovascular events in CKD. The objectives of this study were to 1. Characterize the associations of CKD with presence and morphology of atherosclerotic plaques on carotid magnetic resonance imaging (MRI) and 2. Examine the associations of baseline CKD and carotid atherosclerotic plaques with subsequent cardiovascular events.

Methods
In a subgroup (N = 465) of Systolic Blood Pressure Intervention Trial.
(SPRINT) participants, we measured carotid plaque presence and morphology at baseline and after 30-months with MRI. We examined the associations of CKD (baseline eGFR < 60 ml/min/1.73m2) with progression of carotid plaques and the SPRINT cardiovascular endpoint.

Results
One hundred and ninety six (42%) participants had CKD. Baseline eGFR in the non-CKD and CKD subgroups were 77 ± 14 and 49 ± 8 ml/min/1.73 m2, respectively. Lipid rich necrotic-core plaque was present in 137 (29.5%) participants. In 323 participants with both baseline and follow-up MRI measurements of maximum wall thickness, CKD was not associated with progression of maximum wall thickness (OR 0.62, 95% CI 0.36 to 1.07, p = 0.082). In 96 participants with necrotic core plaque at baseline and with a valid follow-up MRI, CKD was associated with lower odds of progression of necrotic core plaque (OR 0.41, 95% CI 0.17 to 0.95, p = 0.039). There were 28 cardiovascular events over 1764 person-years of follow-up. In separate Cox models, necrotic core plaque (HR 2.59, 95% CI 1.15 to 5.85) but not plaque defined by maximum wall thickness or presence of a plaque component (HR 1.79, 95% CI 0.73 to 4.43) was associated with cardiovascular events. Independent of necrotic core plaque, CKD (HR 3.35, 95% CI 1.40 to 7.99) was associated with cardiovascular events.

Conclusions
Presence of necrotic core in carotid plaque rather than the presence of plaque per se was associated with increased risk of cardiovascular events. We did not find CKD to be associated with faster progression of necrotic core plaques, although both were independently associated with cardiovascular events. Thus, CKD may contribute to cardiovascular disease principally via mechanisms other than atherosclerosis such as arterial media calcification or stiffening.

Trial Registration
NCT01475747, registered on November 21, 2011.
Elevated glucose level leads to rapid COVID-19 progression and high fatality
Authors: Wang Wenjun , Shen Mingwang , Tao Yusha , Fairley Christopher K. , Zhong Qin , Li Zongren , Chen Hui , Ong Jason J. , Zhang Dawei , Zhang Kai , Xing Ning , Guo Huayuan , Qin Enqiang , Guan Xizhou , Yang Feifei , Zhang Sibing , Zhang Lei , He Kunlun 
Published: February 2021

Abstract
Objectives
We aimed to identify high-risk factors for disease progression and fatality for coronavirus disease 2019 (COVID-19) patients.

Methods
We enrolled 2433 COVID-19 patients and used LASSO regression and multivariable cause-specific Cox proportional hazard models to identify the risk factors for disease progression and fatality.

Results
The median time for progression from mild-to-moderate, moderate-to-severe, severe-to-critical, and critical-to-death were 3.0 (interquartile range: 1.8–5.5), 3.0 (1.0–7.0), 3.0 (1.0–8.0), and 6.5 (4.0–16.3) days, respectively. Among 1,758 mild or moderate patients at admission, 474 (27.0%) progressed to a severe or critical stage. Age above 60 years, elevated levels of blood glucose, respiratory rate, fever, chest tightness, c-reaction protein, lactate dehydrogenase, direct bilirubin, and low albumin and lymphocyte count were significant risk factors for progression. Of 675 severe or critical patients at admission, 41 (6.1%) died. Age above 74 years, elevated levels of blood glucose, fibrinogen and creatine kinase-MB, and low plateleta count were significant risk factors for fatality. Patients with elevated blood glucose level were 58% more likely to progress and 3.22 times more likely to die of COVID-19.

Conclusions
Older age, elevated glucose level, and clinical indicators related to systemic inflammatory responses and multiple organ failures, predict both the disease progression and the fatality of COVID-19 patients.
Consumption of antidiabetic medicines in Portugal: results of a temporal data analysis of a thirteen‐year study (2005–2017)
Authors: Moura Artur Mendes , Martins Sofia Oliveira , Raposo João Filipe 
Published: February 2021

Abstract
Background
Studies of drug utilization in patients with diabetes, a chronic disease that can be treated with a wide range of available medicines, have attracted substantial social and clinical interest.

Objective
To characterize antidiabetic medicine consumption between 2005 and 2017, to evaluate the trends of these medicines in mainland Portugal, and to compare district consumption. An additional objective was to perform a statistical analysis on drug consumption in different regions of Portugal.

Methods
A descriptive, longitudinal observational study; the setting was mainland Portugal ( excluding Azores and Madeira).
Each medicine has a respective defined daily dose (DDD). The sum of the DDD, provides the annual consumption in terms of the DDD for each district each year. When calculating the annual average for the resident district population and the number of days in a year, the denominator is expressed as 1000 inhabitants per day (TID).
Main outcome measure: The DDD/TID for mainland Portugal (for all districts) between 2005 and 2017 for antidiabetic medicines.
Information was obtained from the official database of prescription medicine invoices with reimbursement in mainland Portugal.

Results
In mainland Portugal, the antidiabetic medicine consumption was 49.3 DDD/TID in 2005 and 88.2 DDD/TID in 2017. The consumption of insulins and their analogs increased from 10.8% to 17.4% compared to the total consumption of antidiabetic medicines.
In 2017, the level of biguanide consumption was 23.1 DDD/TID, that of sulphonylurea consumption was 15.8 DDD/TID, that of DPP-4 inhibitor consumption was 6.8 DDD/TID, and that of SGLT2 inhibitor consumption was 3.0 DDD/TID. The oral consumption of fixed-dose combinations reached 21.4 DDD/TID.
After employing a geographical division between north and south and between coastal and inland regions, the consumption of several different drugs showed statistically significant differences.

Conclusions
When comparing 2017 with 2005, the panorama was quite different, with higher levels of consumption of antidiabetic medicines, insulins and their analogs, noninsulin medicines, long-acting and fast-acting insulins and their analogs, metformin, DPP-4 inhibitors and, mainly, metformin combined with a DPP-4 inhibitor. The SGLT2 inhibitors achieved a representative consumption.
Different consumption patterns may be related to sociodemographic factors or to clinical practices.
Guideline-based quality assurance: a conceptual framework for the definition of key elements
Authors: Parmelli Elena , Langendam Miranda , Piggott Thomas , Adolfsson Jan , Akl Elie A. , Armstrong David , Braithwaite Jeffrey , Brignardello-Petersen Romina , Follmann Markus , Leś Zbigniew , Meerpohl Joerg J. , Neamtiu Luciana , Qaseem Amir , Rossi Paolo Giorgi , Saz-Parkinson Zuleika , van der Wees Philip J. , Schünemann Holger J. 
Published: February 2021

Abstract
Background
In 2017, the European Commission’s Joint Research Centre (JRC) started developing a methodological framework for a guideline-based quality assurance (QA) scheme to improve cancer quality of care. During the first phase of the work, inconsistency emerged about the use of terminology for the definition, the conceptual underpinnings and the way QA relates to health questions that are answered in guidelines.
The objective of this final of three articles is to propose a conceptual framework for an integrated approach to guideline and QA development and clarify terms and definitions for key elements. This work will inform the upcoming European Commission Initiative on Colorectal Cancer (ECICC).

Methods
A multidisciplinary group of 23 experts from key organizations in the fields of guideline development, performance measurement and quality assurance participated in a mixed method approach including face-to-face dialogue and several rounds of virtual meetings. Informed by results of a systematic literature review that indicated absence of an existing framework and practical examples, we first identified the relations of key elements in guideline-based QA and then developed appropriate concepts and terminology to provide guidance.

Results
Our framework connects the three key concepts of quality indicators, performance measures and performance indicators integrated with guideline development. Quality indicators are constructs used as a guide to monitor, evaluate, and improve the quality of the structure, process and outcomes of healthcare services; performance measures are tools that quantify or describe measurable elements of practice performance; and performance indicators are quantifiable and measurable units or scores of practice, which should be guided by guideline recommendations.

Conclusions
The inconsistency in the way key terms of QA are used and defined has confused the field. Our conceptual framework defines the role, meaning and interactions of the key elements for improving quality in healthcare. It directly builds on the questions asked in guidelines and answered through recommendations. These findings will be applied in the forthcoming ECICC and for the future updates of ECIBC. These are large-scale integrated projects aimed at improving healthcare quality across Europe through the development of guideline-based QA schemes; this will help in implementing and improving our approach.
Impact of COVID-19 on health services utilization in Province-2 of Nepal: a qualitative study among community members and stakeholders
Authors: Singh Devendra Raj , Sunuwar Dev Ram , Shah Sunil Kumar , Karki Kshitij , Sah Lalita Kumari , Adhikari Bipin , Sah Rajeeb Kumar 
Published: February 2021

Abstract
Background
The COVID-19 pandemic has posed unprecedented challenges and threats to the health care system, particularly affecting the effective delivery of essential health services in resource-poor countries such as Nepal. This study aimed to explore community perceptions of COVID-19 and their experiences towards health services utilization during the pandemic in Province-2 of Nepal.

Methods
The semi-structured qualitative interviews were conducted among purposively selected participants (n = 41) from a mix of rural and urban settings in all districts (n = 8) of the Province 2 of Nepal. Virtual interviews were conducted between July and August 2020 in local languages. The data were analyzed using thematic network analysis in NVivo 12 Pro.

Results
The findings of this research are categorized into four global themes: i) Community and stakeholders’ perceptions towards COVID-19; ii) Impact of COVID-19 and lockdown on health services delivery; iii) Community perceptions and experiences of health services during COVID-19; and iv) COVID-19: testing, isolation, and quarantine services. Most participants shared their experience of being worried and anxious about COVID-19 and reported a lack of awareness, misinformation, and stigma as major factors contributing to the spread of COVID-19. Maternity services, immunization, and supply of essential medicine were found to be the most affected areas of health care delivery during the lockdown. Participants reported that the interruptions in health services were mostly due to the closure of health services at local health care facilities, limited affordability, and involvement of private health sectors during the pandemic, fears of COVID-19 transmission among health care workers and within health centers, and disruption of transportation services. In addition, the participants expressed frustrations on poor testing, isolation, and quarantine services related to COVID-19, and poor accountability from the government at all levels towards health services continuation/management during the COVID-19 pandemic.

Conclusions
This study found that essential health services were severely affected during the COVID-19 pandemic in all districts of Province-2. It is critical to expand and continue the service coverage, and its quality (even more during pandemics), as well as increase public-private sector engagement to ensure the essential health services are available for the population.
Clinical course of IPF in Italian patients during 12 months of observation: results from the FIBRONET observational study
Authors:   the FIBRONET study group, Poletti V. , Vancheri C. , Albera C. , Harari S. , Pesci A. , Metella R. R. , Campolo B. , Crespi G. , Rizzoli S. 
Published: February 2021

Abstract
Background
FIBRONET was an observational, multicentre, prospective cohort study investigating the baseline characteristics, clinical course of disease and use of antifibrotic treatment in Italian patients with idiopathic pulmonary fibrosis (IPF).

Methods
Patients aged ≥ 40 years diagnosed with IPF within the previous 3 months at 20 Italian centres were consecutively enrolled and followed up for 12 months, with evaluations at 3, 6, 9 and 12 months. The primary objective was to describe the clinical course of IPF over 12 months of follow-up, including changes in lung function measured by % predicted forced vital capacity (FVC% predicted).

Results
209 patients (82.3% male, mean age 69.54 ± 7.43 years) were enrolled. Mean FVC% predicted was relatively preserved at baseline (80.01%). The mean time between IPF diagnosis and initiation of antifibrotic therapy was 6.38 weeks; 72.3% of patients received antifibrotic therapy within the first 3 months of follow-up, and 83.9% within 12 months of follow-up. Mean FVC% predicted was 80.0% at baseline and 82.2% at 12 months, and 47.4% of patients remained stable (i.e. had no disease progression) in terms of FVC% predicted during the study.

Conclusions
FIBRONET is the first prospective, real-life, observational study of patients with IPF in Italy. The short time between diagnosis and initiation of antifibrotic therapy, and the stable lung function between baseline and 12 months, suggest that early diagnosis and prompt initiation of antifibrotic therapy may preserve lung function in patients with IPF.
Trial registration: NCT02803580
Inhibition of the Otub1/c-Maf axis by the herbal acevaltrate induces myeloma cell apoptosis
Authors: Sun Tong , Xu Yujia , Xu Zhuan , Cao Biyin , Zhang Zubin , Wang Qi , Kong Yan , Mao Xinliang 
Published: February 2021

Abstract
Background
The oncogenic transcript factor c-Maf is stabilized by the deubiquitinase Otub1 and promotes myeloma cell proliferation and confers to chemoresistance. Inhibition of the Otub1/c-Maf axis is a promising therapeutic target, but there are no inhibitors reported on this specific axis.

Methods
A luciferase assay was applied to screen potential inhibitors of Otub1/c-Maf. Annexin V staining/flow cytometry was applied to evaluate cell apoptosis. Immunoprecipitation was applied to examine protein ubiquitination and interaction. Xenograft models in nude mice were used to evaluate anti-myeloma activity of AVT.

Results
Acevaltrate (AVT), isolated from Valeriana glechomifolia, was identified based on a bioactive screen against the Otub1/c-Maf/luciferase system. AVT disrupts the interaction of Otub1/c-Maf thus inhibiting Otub1 activity and leading to c-Maf polyubiquitination and subsequent degradation in proteasomes. Consistently, AVT inhibits c-Maf transcriptional activity and downregulates the expression of its target genes key for myeloma growth and survival. Moreover, AVT displays potent anti-myeloma activity by triggering myeloma cell apoptosis in vitro and impairing myeloma xenograft growth in vivo but presents no marked toxicity.

Conclusions
The natural product AVT inhibits the Otub1/c-Maf axis and displays potent anti-myeloma activity. Given its great safety and efficacy, AVT could be further developed for MM treatment.