bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ignoring instead of chasing after coagulation factor VII during warfarin management: an interrupted time series study
Authors: Oskarsdottir Alma R. , Gudmundsdottir Brynja R. , Jensdottir Hulda M. , Flygenring Bjorn , Palsson Ragnar , Onundarson Pall T. 
Published: January 2021

Abstract
During warfarin management, variability in prothrombin time-based international normalized ratio (PT-INR) is caused, in part, by clinically inconsequential fluctuations in factor VII (FVII). The new factor II and X (Fiix)-prothrombin time (Fiix-PT) and Fiix-normalized ratio (Fiix-NR), unlike PT-INR, are only affected by reduced FII and FX. We assessed the incidence of thromboembolism (TE) and major bleeding (MB) in all 2667 patients on maintenance-phase warfarin managed at our anticoagulation management service during 30 months; 12 months prior to and 18 months after replacing PT-INR monitoring with Fiix-NR monitoring. Months 13 to 18 were predefined as transitional months. Using 2-segmented regression, a breakpoint in the monthly incidence of TE became evident 6 months after test replacement, that was followed by a 56% reduction in incidence (from 2.82% to 1.23% per patient-year; P = .019). Three-segmented regression did not find any significant trend in TE incidence (slope, +0.03) prior to test replacement; however, during months 13 to 18 and 19 to 30, the incidence of TE decreased gradually (slope, −0.12; R2 = 0.20; P = .007). The incidence of MB (2.79% per patient-year) did not differ. Incidence comparison during the 12-month Fiix and PT periods confirmed a statistically significant reduction (55-62%) in TE. Fiix monitoring reduced testing, dose adjustments, and normalized ratio variability and prolonged testing intervals and time in range. We conclude that ignoring FVII during Fiix-NR monitoring in real-world practice stabilizes the anticoagulant effect of warfarin and associates with a major reduction in TEs without increasing bleeding.
A phase 3 double-blind study of the addition of tocilizumab vs placebo to cyclosporin/methotrexate GVHD prophylaxis
Authors: Kennedy Glen A. , Tey Siok-Keen , Buizen Luke , Varelias Antiopi , Gartlan Kate H. , Curley Cameron , Olver Stuart D. , Chang Karshing , Butler Jason P. , Misra Ashish , Subramoniapillai Elango , Morton A. James , Durrant Simon , Henden Andrea S. , Moore John , Ritchie David , Gottlieb David , Cooney Julian , Paul Sanjoy K. , Hill Geoffrey R. 
Published: January 2021

Abstract
We determined the efficacy of tocilizumab (TCZ) in preventing grade 2-4 acute graft-versus-host disease (aGVHD) in patients with acute leukemia or myelodysplasia undergoing matched sibling donor (MSD) or volunteer unrelated donor (VUD) allogeneic stem cell transplantation after myeloablative or reduced-intensity conditioning across 5 Australian centers. A total of 145 patients (50 MSD, 95 VUD) were randomly assigned to placebo or TCZ on day −1. All patients received T-cell–replete peripheral blood stem cell grafts and graft-versus-host disease (GVHD) prophylaxis with cyclosporin/methotrexate. A planned substudy analyzed the VUD cohort. With a median follow-up of 746 days, the incidence of grade 2-4 aGVHD at day 100 for the entire cohort was 36% for placebo vs 27% for TCZ (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.38-1.26; P = .23) and 45% vs 32% (HR, 0.61; 95% CI, 0.31-1.22; P = .16) for the VUD subgroup. The incidence of grade 2-4 aGVHD at day 180 for the entire cohort was 40% for placebo vs 29% for TCZ (HR, 0.68; 95% CI, 0.38-1.22; P = .19) and 48% vs 32% (HR, 0.59; 95% CI, 0.30-1.16; P = .13) for the VUD subgroup. Reductions in aGVHD were predominantly in grade 2 disease. For the entire cohort, transplant-related mortality occurred in 8% vs 11% of placebo-treated vs TCZ-treated patients, respectively (P = .56), and overall survival was 79% vs 71% (P = .27). Median day to neutrophil and platelet engraftment was delayed by 2 to 3 days in TCZ-treated patients, whereas liver toxicity and infectious complications were similar between groups. In this phase 3 randomized double-blind trial, TCZ showed nonsignificant trends toward reduced incidence of grade 2-4 aGVHD in recipients from HLA-matched VUDs but no improvements in long term-survival.
Central airway and peripheral lung structures in airway disease-dominant COPD
Authors: Tanabe Naoya , Shimizu Kaoruko , Terada Kunihiko , Sato Susumu , Suzuki Masaru , Shima Hiroshi , Oguma Akira , Oguma Tsuyoshi , Konno Satoshi , Nishimura Masaharu , Hirai Toyohiro 
Published: January 2021

The concept that the small airway is a primary pathological site for all COPD phenotypes has been challenged by recent findings that the disease starts from the central airways in COPD subgroups and that a smaller central airway tree increases COPD risk. This study aimed to examine whether the computed tomography (CT)-based airway disease-dominant (AD) subtype, defined using the central airway dimension, was less associated with small airway dysfunction (SAD) on CT, compared to the emphysema-dominant (ED) subtype.COPD patients were categorised into mild, AD, ED and mixed groups based on wall area per cent (WA%) of the segmental airways and low attenuation volume per cent in the Kyoto–Himeji (n=189) and Hokkaido COPD cohorts (n=93). The volume per cent of SAD regions (SAD%) was obtained by nonrigidly registering inspiratory and expiratory CT.The AD group had a lower SAD% than the ED group and similar SAD% to the mild group. The AD group had a smaller lumen size of airways proximal to the segmental airways and more frequent asthma history before age 40 years than the ED group. In multivariable analyses, while the AD and ED groups were similarly associated with greater airflow limitation, the ED, but not the AD, group was associated with greater SAD%, whereas the AD, but not the ED, group was associated with a smaller central airway size.The CT-based AD COPD subtype might be associated with a smaller central airway tree and asthma history, but not with peripheral lung pathologies including small airway disease, unlike the ED subtype.
The safety of cardioselective β1-blockers in asthma: literature review and search of global pharmacovigilance safety reports
Authors: Bennett Miriam , Chang Catherina L. , Tatley Michael , Savage Ruth , Hancox Robert J. 
Published: January 2021

IntroductionBeta-blockers are key in the management of cardiovascular diseases but blocking airway β2-receptors can cause severe and sometimes fatal bronchoconstriction in people with asthma. Although cardioselective β1-blockers may be safer than non-selective β-blockers, they remain relatively contraindicated and under-prescribed. We review the evidence of the risk associated with cardioselective β1-blocker use in asthma.MethodsWe searched “asthma” AND “beta-blocker” in PubMed and EmbaseOvid from start to May 2020. The World Health Organization (WHO) global database of individual case safety reports (VigiBase) was searched for reports of fatal asthma or bronchospasm and listed cardioselective β1-blocker use (accessed February 2020). Reports were examined for evidence of pre-existing asthma.ResultsPubMed and EmbaseOvid searches identified 304 and 327 publications, respectively. No published reports of severe or fatal asthma associated with cardioselective β1-blockers were found. Three large observational studies reported no increase in asthma exacerbations with cardioselective β1-blocker treatment. The VigiBase search identified five reports of fatalities in patients with pre-existing asthma and reporting asthma or bronchospasm during cardioselective β1-blocker use. Four of these deaths were unrelated to cardioselective β1-blocker use. The circumstances of the fifth death were unclear.ConclusionsThere were no published reports of cardioselective β1-blockers causing asthma death. Observational data suggest that cardioselective β1-blocker use is not associated with increased asthma exacerbations. We found only one report of an asthma death potentially caused by cardioselective β1-blockers in a patient with asthma in a search of VigiBase. The reluctance to use cardioselective β1-blockers in people with asthma is not supported by this evidence.
Emergency medicine matters: epidemiology of medical pathology and changes in patient outcomes after implementation of a post-graduate training program at a Tertiary Teaching Hospital in Kigali, Rwanda
Authors: Moretti Katelyn , Uwamahoro Doris Lorette , Naganathan Sonya , Uwamahoro Chantal , Karim Naz , Nkeshimana Menales , Aluisio Adam R. 
Published: January 2021

AbstractBackgroundEmergency care is a new but growing specialty across Africa where medical conditions have been estimated to account for 92% of all disability-adjusted life years. This study describes the epidemiology of medical emergencies and the impact of formalized emergency care training on patient outcomes for medical conditions in Rwanda.MethodsA retrospective cohort study was performed using a database of randomly sampled patients presenting to the emergency center (EC) at the University Teaching Hospital of Kigali. All patients, > 15 years of age treated for medical emergencies pre- and post-implementation of an Emergency Medicine (EM) residency training program were eligible for inclusion. Patient characteristics and final diagnosis were described by time period (January 2013–September 2013 versus September 2015–June 2016). Univariate chi-squared analysis was performed for diagnoses, EC interventions, and all cause EC and inpatient mortality stratified by time period.ResultsA random sample of 1704 met inclusion with 929 patients in the pre-residency time period and 775 patients in the post-implementation period. Demographics, triage vital signs, and shock index were not different between time periods. Most frequent diagnoses included gastrointestinal, infectious disease, and neurologic pathology. Differences by time period in EC management included antibiotic use (37.2% vs. 42.2%,p= 0.04), vasopressor use (1.9% vs. 0.5%,p= 0.01), IV crystalloid fluid (IVF) use (55.5% vs. 47.6%,p= 0.001) and mean IVF administration (2057 ml vs. 2526 ml,p< 0.001). EC specific mortality fell from 10.0 to 1.4% (p< 0.0001) across time periods.ConclusionsMortality rates fell across top medical diagnoses after implementation of an EM residency program. Changes in resuscitation care may explain, in part, this mortality decrease. This study demonstrates that committing to emergency care can potentially have large effects on reducing mortality.
Regulation of the antennal transcriptome of the dengue vector, Aedes aegypti, during the first gonotrophic cycle
Authors: Hill Sharon Rose , Taparia Tanvi , Ignell Rickard 
Published: January 2021

AbstractBackgroundIn the light of dengue being the fastest growing transmissible disease, there is a dire need to identify the mechanisms regulating the behaviour of the main vectorAedes aegypti. Disease transmission requires the female mosquito to acquire the pathogen from a blood meal during one gonotrophic cycle, and to pass it on in the next, and the capacity of the vector to maintain the disease relies on a sustained mosquito population.ResultsUsing a comprehensive transcriptomic approach, we provide insight into the regulation of the odour-mediated host- and oviposition-seeking behaviours throughout the first gonotrophic cycle. We provide clear evidence that the age and state of the female affects antennal transcription differentially. Notably, the temporal- and state-dependent patterns of differential transcript abundance of chemosensory and neuromodulatory genes extends across families, and appears to be linked to concerted differential modulation by subsets of transcription factors.ConclusionsBy identifying these regulatory pathways, we provide a substrate for future studies targeting subsets of genes across disparate families involved in generating key vector behaviours, with the goal to develop novel vector control tools.
Adherence to prescription guidelines and achievement of treatment goals among persons with coronary heart disease in Tromsø 7
Authors: Pedersen Elisabeth , Garcia Beate Hennie , Halvorsen Kjell H. , Eggen Anne Elise , Schirmer Henrik , Waaseth Marit 
Published: January 2021

Abstract
Background
Adherence to clinical practice guidelines for coronary heart disease (CHD) reduces morbidity, mortality and treatment costs. We aimed to describe and compare adherence to prescription guidelines for persons with CHD, and explore its association with treatment goal achievement.

Method
We included all participants reporting myocardial infarction, angina, percutaneous coronary intervention and/or coronary artery bypass surgery in the seventh wave of the Tromsø Study (2015–2016, n = 1483). Medication use and treatment goal measures (blood pressure, low-density lipoprotein (LDL)-cholesterol and HbA1c) were compared to clinical practice guidelines on secondary CHD prevention. Propensity score matched logistic regression was used to assess the association between the use of antihypertensive drugs and achievement of treatment goal for blood pressure, and the use of lipid-lowering drugs (LLDs) and achievement of treatment goal for LDL-cholesterol.

Results
The prevalence of pharmacological CHD treatment was 76% for LLDs, 72% for antihypertensive drugs and 66% for acetylsalicylic acid. The blood pressure goal (< 140/90 mmHg, < 140/80 mmHg if diabetic) was achieved by 58% and the LDL-cholesterol goal (< 1.8 mmol/l or < 70 mg/dL) by 9%. There was a strong association between using LLDs and achieving the treatment goal for LDL-cholesterol (OR 14.0, 95% CI 3.6–54.7), but not between using antihypertensive drugs and blood pressure goal achievement (OR 1.4, 95% CI 0.7–2.7).

Conclusion
Treatment goal achievement of LDL-cholesterol and blood pressure was low, despite the relatively high use of LLDs and antihypertensive drugs. Further research is needed to find the proper actions to increase achievement of the treatment goals.
Baseline thrombopoietin level is associated with platelet count improvement in thrombocytopenic chronic hepatitis C patients after successful direct-acting antiviral agent therapy
Authors: Chen Yen-Chun , Ko Ping-Hung , Lee Chi-Che , Tseng Chih-Wei , Tseng Kuo-Chih 
Published: January 2021

Abstract
Background
Thrombocytopenia can rapidly improve in chronic hepatitis C (CHC) patients receiving direct-acting antiviral agents (DAA). The role of baseline (BL) thrombopoietin (TPO) in this phenomenon is unclear.

Methods
From June 2016 to February 2019, a total of 104 CHC patients receiving DAA, with a sustained virologic response and BL thrombocytopenia, at Dalin Tzu Chi Hospital, were enrolled in this retrospective study. Significant platelet count improvement and platelet count improvement ratio were analyzed for correlation with BL TPO.

Results
This cohort included 40 men (38.5%). Seventy-two (69.2%) patients had advanced fibrosis. The platelet count [median (range)] increased from 110.5 (32–149) × 103/µL at BL to 116.5 (40–196) and 118.0 (35–275) × 103/µL at end of treatment (EOT) and 12 weeks after EOT (P12), respectively, (EOT vs. BL, P < 0.001; P12 vs. BL, P < 0.001). BL TPO was positively correlated with significant platelet count improvement (P < 0.001), platelet count improvement ratio at EOT (P = 0.004), and P12 (P < 0.001). The area under the receiver operating characteristic curve and optimal cutoffs (pg/ml) were 0.77 (95% confidence interval, 0.67–0.86) and 120, respectively, for significant platelet count improvement prediction. The sensitivity, specificity, and accuracy were 88.6%, 71.7%, and 78.8%, respectively.

Conclusions
BL TPO level might be a useful marker for predicting significant platelet count improvement in thrombocytopenic patients after successful DAA therapy.
Using Baidu search values to monitor and predict the confirmed cases of COVID-19 in China: – evidence from Baidu index
Authors: Tu Bizhi , Wei Laifu , Jia Yaya , Qian Jun 
Published: January 2021

Abstract
Background
New coronavirus disease 2019 (COVID-19) has posed a severe threat to human life and caused a global pandemic. The current research aimed to explore whether the search-engine query patterns could serve as a potential tool for monitoring the outbreak of COVID-19.

Methods
We collected the number of COVID-19 confirmed cases between January 11, 2020, and April 22, 2020, from the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). The search index values of the most common symptoms of COVID-19 (e.g., fever, cough, fatigue) were retrieved from the Baidu Index. Spearman’s correlation analysis was used to analyze the association between the Baidu index values for each COVID-19-related symptom and the number of confirmed cases. Regional distributions among 34 provinces/ regions in China were also analyzed.

Results
Daily growth of confirmed cases and Baidu index values for each COVID-19-related symptom presented robust positive correlations during the outbreak (fever: rs=0.705, p=9.623× 10− 6; cough: rs=0.592, p=4.485× 10− 4; fatigue: rs=0.629, p=1.494× 10− 4; sputum production: rs=0.648, p=8.206× 10− 5; shortness of breath: rs=0.656, p=6.182× 10–5). The average search-to-confirmed interval (STCI) was 19.8 days in China. The daily Baidu Index value’s optimal time lags were the 4 days for cough, 2 days for fatigue, 3 days for sputum production, 1 day for shortness of breath, and 0 days for fever.

Conclusion
The searches of COVID-19-related symptoms on the Baidu search engine were significantly correlated to the number of confirmed cases. Since the Baidu search engine could reflect the public’s attention to the pandemic and the regional epidemics of viruses, relevant departments need to pay more attention to areas with high searches of COVID-19-related symptoms and take precautionary measures to prevent these potentially infected persons from further spreading.
An open label, randomised controlled trial of rifapentine versus rifampicin based short course regimens for the treatment of latent tuberculosis in England: the HALT LTBI pilot study
Authors: Surey J. , Stagg H. R. , Yates T. A. , Lipman M. , White P. J. , Charlett A. , Muñoz L. , Gosce L. , Rangaka M. X. , Francis M. , Hack V. , Kunst H. , Abubakar I. 
Published: January 2021

Abstract
Background
Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks.

Methods
An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid (‘intervention’) or a daily combination of rifampicin/isoniazid (‘standard’), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded.

Results
Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7–91.4), compared with 19 of 25 (76.0%, CI 54.9–90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms.

Conclusion
In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment.

Trial registration
The trial was funded by the NIHR, UK and registered with ISRCTN (26/02/2013-No.04379941).
Past eight-year malaria data in Gedeo zone, southern Ethiopia: trend, reporting-quality, spatiotemporal distribution, and association with socio-demographic and meteorological variables
Authors: Molla Eshetu , Behaksra Sinknesh Wolde , Tadesse Fitsum G. , Dugassa Sisay , Gadisa Endalamaw , Mamo Hassen 
Published: January 2021

Abstract
Background
Informed decision making is underlined by all tiers in the health system. Poor data record system coupled with under- (over)-reporting of malaria cases affects the country’s malaria elimination activities. Thus, malaria data at health facilities and health offices are important particularly to monitor and evaluate the elimination progresses. This study was intended to assess overall reported malaria cases, reporting quality, spatiotemporal trends and factors associated in Gedeo zone, South Ethiopia.

Methods
Past 8 years retrospective data stored in 17 health centers and 5 district health offices in Gedeo Zone, South Ethiopia were extracted. Malaria cases data at each health center with sociodemographic information, between January 2012 and December 2019, were included. Meteorological data were obtained from the national meteorology agency of Ethiopia. The data were analyzed using Stata 13.

Results
A total of 485,414 suspected cases were examined for malaria during the previous 8 years at health centers. Of these suspects, 57,228 (11.79%) were confirmed malaria cases with an overall decline during the 8-year period. We noted that 3758 suspected cases and 467 confirmed malaria cases were not captured at the health offices. Based on the health centers records, the proportions of Plasmodium falciparum (49.74%) and P. vivax (47.59%) infection were nearly equivalent (p = 0.795). The former was higher at low altitudes while the latter was higher at higher altitudes. The over 15 years of age group accounted for 11.47% of confirmed malaria cases (p < 0.001). There was high spatiotemporal variation: the highest case record was during Belg (12.52%) and in Dilla town (18,150, 13.17%, p < 0.001) which is located at low altitude. Monthly rainfall and minimum temperature exhibited strong associations with confirmed malaria cases.

Conclusion
A notable overall decline in malaria cases was observed during the eight-year period. Both P. falciparum and P. vivax were found at equivalent endemicity level; hence control measures should continue targeting both species. The noticed under reporting, the high malaria burden in urban settings, low altitudes and Belg season need spatiotemporal consideration by the elimination program.