bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of Multiple-Batch Approaches to Pharmacokinetic Bioequivalence Testing for Orally Inhaled Drug Products with Batch-to-Batch Variability
Authors: Burmeister Getz Elise , Carroll Kevin J. , Christopher J. David , Morgan Beth , Haughie Scott , Cavecchi Alessandro , Wiggenhorn Christopher , Beresford Hayden , Strickland Helen , Lyapustina Svetlana 
Published: August 2021

AbstractBatch-to-batch pharmacokinetic (PK) variability of orally inhaled drug products has been documented and can render single-batch PK bioequivalence (BE) studies unreliable; results from one batch may not be consistent with a repeated study using a different batch, yet the goal of PK BE is to deliver a product comparison that is interpretable beyond the specific batches used in the study. We characterized four multiple-batch PK BE approaches to improve outcome reliability without increasing the number of clinical study participants. Three approaches include multiple batches directly in the PK BE study with batch identity either excluded from the statistical model (“Superbatch”) or included as a fixed or random effect (“Fixed Batch Effect,” “Random Batch Effect”). A fourth approach uses a bio-predictive in vitro test to screen candidate batches, bringing the median batch of each product into the PK BE study (“Targeted Batch”). Three of these approaches (Fixed Batch Effect, Superbatch, Targeted Batch) continue the single-batch PK BE convention in which uncertainty in the Test/Reference ratio estimate due to batch sampling is omitted from the Test/Reference confidence interval. All three of these approaches provided higher power to correctly identify true bioequivalence than the standard single-batch approach with no increase in clinical burden. False equivalence (type I) error was inflated above the expected 5% level, but multiple batches controlled type I error better than a single batch. The Random Batch Effect approach restored 5% type I error, but had low power for small (e.g., <8) batch sample sizes using standard [0.8000, 1.2500] bioequivalence limits.
Diabetes and Outcomes Following Personalized Antiplatelet Therapy in Coronary Artery Disease Patients Who Have Undergone PCI
Authors: Zheng Ying-Ying , Wu Ting-Ting , Yang Yi , Hou Xian-Geng , Chen You , Ma Xiang , Ma Yi-Tong , Zhang Jin-Ying , Xie Xiang 
Published: August 2021

Abstract

Context
A personalized antiplatelet therapy guided by a novel platelet function testing (PFT), PL-12, is considered an optimized treatment strategy in stable coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). However, the safety and efficacy of any dual-antiplatelet therapy (DAPT) strategy may differ in relation to diabetes status.

Objective
The aim of this study was to compare the outcomes of PFT-guided personalized DAPT in stable CAD patients with and without diabetes mellitus.

Methods
The PATH-PCI trial randomly assigned 2285 stable CAD patients to either personalized antiplatelet therapy or standard antiplatelet treatment. We investigated the association and interaction of diabetes on clinical outcomes across 2 treatment groups.

Results
We did not find a significant difference between the personalized group and the standard group in net adverse clinical events in either diabetes patients (10.3% vs 13.4%, P = .224) or in the nondiabetic group (3.1% vs 5.0%, P = .064). In diabetes patients (n = 646, 28.3%), the overall ischemic event rates were significantly low (6.8% vs 11.3%, HR = 0.586, 95% CI, 0.344-0.999, P = .049) and the bleeding event rates did not differ between the 2 groups (3.5% vs 3.3%, HR = 1.066, 95% CI, 0.462-2.458, P = .882). Similarly, in nondiabetic patients, the overall ischemic event rates were significantly low (1.8% vs 4.2%, HR = 0.428, 95% CI, 0.233-0.758, P = .006) and the bleeding event rates did not differ between the 2 groups (1.6% vs 0.9%, HR = 1.802, 95% CI: 0.719-4.516, P = .209).

Conclusion
The present study suggests that personalized antiplatelet therapy according to PFT can reduce ischemic events but not increase bleedings in stable CAD patients with or without diabetes who have undergone PCI.
Health of Immigrant Children: The Role of Immigrant Generation, Exogamous Family Setting, and Family Material and Social Resources
Authors: Loi Silvia , Pitkänen Joonas , Moustgaard Heta , Myrskylä Mikko , Martikainen Pekka 
Published: August 2021

AbstractAlthough the children of first-generation immigrants tend to have better health than the native population, the health advantage of the children of immigrant families deteriorates over generations. It is, however, poorly understood where on the generational health assimilation spectrum children with one immigrant and one native parent (i.e., exogamous families) lie, to what extent family resources explain health assimilation, and whether the process of assimilation varies across health conditions. We seek to extend our understanding of the process of health assimilation by analyzing the physical and mental health of immigrant generations, assessing the role of exogamous family arrangements, and testing the contributions of family material and social resources to children's outcomes. We use register-based longitudinal data on all children residing in Finland, born in 1986–2000, and alive in 2000; these data are free of reporting bias and loss to follow-up. We estimate the risk of receiving inpatient and outpatient care for somatic conditions, psychopathological disorders, and injuries by immigrant generation status. Our results show evidence of a negative health assimilation process, with both first- and second-generation immigrant children having a higher prevalence of physical problems and particularly mental health problems than native children that is only partially explained by family resources. We find that the children of exogamous families are at especially high risk of developing psychopathological disorders. These results provide strong support for the hypothesis that children of exogamous families constitute a specific health risk group and that the impact on children's health of family social and material resources seems to be secondary to other unobserved factors.
Changing epidemiology of dengue in Sri Lanka—Challenges for the future
Authors: Malavige Gathsaurie Neelika , Jeewandara Chandima , Ghouse Azhar , Somathilake Gayasha , Tissera Hasitha 
Published: August 2021

Background
Dengue infections are on the rise in Sri Lanka and are spreading to all areas in the country. Here, we discuss the changes in dengue epidemiology in Sri Lanka in relation to changes in age distribution, changes in seroprevalence rates over time, and possible reasons contributing to such changes.

Methods and findings
Although the incidence of dengue increased 20-fold from the year 2000 to 2012 and a further 3-fold from 2012 to 2019, this increase is not reflected in a similar increase in the age-stratified seropositivity rates for dengue. For instance, the annual seroconversion rates were 0.76% in 2013 and 0.91% in 2017. The annual seroconversion rates in the 6 to 17 age group were 1.5% per year in 2003, 3.9% in 2013, and 4.1% in 2017. In addition, although a 13-fold increase in dengue was seen in those who were <19 years of age, a 52.4-fold increase was seen in the 40- to 59-year age group. The case fatality rates (CFRs) have similarly changed, with 61.8% of deaths occurring in those <19 years of age in the year 2000, while in 2012 to 2018, the highest CFR were seen in those who were aged 20 to 39 years. Although there has been a marked increase in the number of cases, the vector densities did not change during a 4-year period. The proportion of adult individuals experiencing a secondary dengue infection has also remained between 65% and 75% between the years 2004 and 2018.

Conclusions
A change in the ratio of symptomatic to asymptomatic infections can give rise to changes in the reported incidence of dengue. In order to take an appropriate policy decision in dengue control activities, it would be important to study the changes in virus serotypes, vector dispersion, and densities. Further, the contribution of the rise in metabolic diseases to an increase in the symptomatic as well as more severe infections due to dengue is explored.
Incidence and predictors of mortality among patients with head injury admitted to Hawassa University Comprehensive Specialized Hospital, Southern Ethiopia: A retrospective follow-up study
Authors: Assele Desalegn Dawit , Lendado Tigabu Addisu , Awato Merid Assefa , Workie Shimelash Bitew , Faltamo Wolde Facha 
Published: August 2021

Introduction
Head injury is the leading cause of morbidity and mortality throughout the world, especially in resource-limited countries including Ethiopia. However, little is known about the mortality rate and its predictors among these patients in Ethiopia. Thus, the study aims to assess the incidence rate of mortality and its predictors among patients with head injury admitted at Hawassa University Comprehensive Specialized Hospital.

Methods
Institutional based retrospective follow-up study was conducted among 1220 randomly selected head injury patients admitted from July 2017 to July 2019. Bivariable and multivariable Cox regression models were fitted to identify the predictors of mortality. Proportionality assumption was tested by a global test based on the Schoenfeld residuals test.

Results
The incidence of the mortality rate was 2.26 (95%CI: 1.9–2.6) per 100-person day observation. The independent predictors of time to death were age above 65 years (AHR:3.49, 95%CI:1.63, 7.48), severe TBI (AHR: 8.8, 95%CI:5.13, 15.0), moderate TBI (AHR:3, 95%CI:1.73,5.31), hypotension (AHR:1.72, 95%CI: 1.11,2.66), hypoxia (AHR:1.92, 95%CI: 1.33,2.76), hyperthermia (AHR:1.8, 95%CI: 1.23,2.63) and hypoglycemic (AHR:1.94, 95%CI: 1.34, 2.81) positively associated with mortality, while underwent neurosurgery was negatively associated with mortality (AHR: 0.25, 95% CI: 0.11,0.53).

Conclusion
The incidence of mortality rate among head injury patients was high. Older age, moderate and severe TBI, hypotension and hypoxia at admission, neurosurgical procedure, and the episode of hyperthermia and hypoglycemia during hospitalization were the independent predictors of mortality among head injury patients. Therefore, intervention to reduce earlier deaths should focus on the prevention of secondary brain insults.
Visual impairment and its associated factors among medical and health sciences students at the University of Gondar, Northwest Ethiopia
Authors: Getnet Mihret , Akalu Yonas , Dagnew Baye , Gela Yibeltal Yismaw , Belsti Yitayeh , Diress Mengistie , Fekadu Sofonias Addis , Seid Mohammed Abdu 
Published: August 2021

Background
Visual impairment (VI) is a decreased ability to see things which is critical problem for health professionals and students to whom normal vision is essential for their daily activity. If it is not timely managed, visual impairment leads to physical, psychological, and socio-economic malfunctions to the victims and nation. Despite the above impacts, currently there is no study in Ethiopia on this topic. Therefore, this study aimed to determine the prevalence of visual impairment and its associated factors among Medical and Health Science students at the University of Gondar.

Methods
A cross-sectional study was conducted from January to March 2020 among Medical and Health Science students. After recruiting study participants using systematic random sampling technique, we applied pre-tested self-administered questionnaire for sociodemographic variables and also visual acuity measurement was performed using Snellen chart placed at a distance of 6 meters. Visual acuity tested separately for each eye and for both eyes in a well- illuminated area. Pinhole was used for those participants with a visual acuity of < 6/9. Participants with a presenting visual acuity of < 6/12 in the better eye were diagnosed as having visual impairment. Epi data version 3.1 and stata version 14 were used for data entry and statistical analysis, respectively. Binary logistic regression was used, and the Adjusted Odds Ratio (AOR) with the 95% Confidence Interval (CI) was reported to declare the statistical significance and strength of association between VI and independent variables.

Results
A total of 654 students were screened for visual acuity. The prevalence of visual impairment was 12.5% (95% CI: 10.21, 15.31). Age above 25 years (AOR = 1.8; 95% CI: 1.02, 3.26) and current alcohol drinking (AOR = 2.9; 95% CI: 1.7, 5.00), were statistically significant factors of visual impairment.

Conclusion
The prevalence of visual impairment among medical and health science students was high. Age of study participant and current alcohol consumption were statically significant factors. This study warrants the routine screening of Medical and Health science students for visual impairment.
Managerial overconfidence in capital structure decisions and its link to aggregate demand: An agent-based model perspective
Authors: Rzeszutek Marcin , Godin Antoine , Szyszka Adam , Augier Stanislas 
Published: August 2021

Objective
This study aims to connect two strands of the psychology and economics literature, i.e., behavioural finance and agent-based macroeconomics, to assess the impact of managerial overconfidence at the micro and macro levels of the economy as a whole.

Method
We build a macroeconomic stock-flow consistent agent-based model that is calibrated for the specific case of Poland to explore whether the overconfidence of top corporate managers in the context of their initial capital structure decisions is detrimental for the firms being managed in this way, the financial market dynamics, and the selected macroeconomic indicators. We model heterogeneous firms with different capital structure decision criteria depending on their degree of managerial overconfidence. Our model also includes a complete macroeconomic closure with aggregated households, capital producers, banking, and a public sector.

Results
We find that firms with overconfident managers outperform in terms of investment and size but are also more fragile, thereby making them more likely to default. Finally, we run policy shocks and show that while investors’ flight to liquidity creates financial turmoil and increases the probability of default.

Conclusions
This paper contributes to the knowledge base by linking behavioural corporate finance and agent-based macroeconomics. In general, the excess overconfidence on the micro level, either an increase in the proportion of overconfident firms or a higher degree of overconfidence among managers, has a strong destabilizing impact on the economy as a whole on the macro level.
The Cardiorespiratory fitness of children and adolescents in Tibet at altitudes over 3,500 meters
Authors: Fan Chaoqun , Sun Ruizhe , Nie Mingjian , Wang Mei , Yao Zhi , Feng Qiang , Xu Wenfeng , Yuan Runzi , Gao Zhongfang , Cheng Qiaorui , Wang Jingjing 
Published: August 2021

Background
Cardiorespiratory fitness (CRF) is the core element of health-related physical fitness evaluation. High pressure and low oxygen in Tibet (over 3,500 m above sea level) may negatively impact the residents’ CRF. The 20-m shuttle run test (20mSRT) is the most popular field-based assessment and estimate of CRF in children and adolescents worldwide. However, normative CRF data for the children and adolescents residing in China’s plateau region are unavailable, which prevents comparability among those living at high-altitudes around the world.

Purpose
To measure the CRF of Chinese children and adolescents aged 9–18 years living in Tibet at altitudes exceeding 3,500 m, and to identify correlations between this metric and demographic characteristics (age, sex, and ethnicity). These data were then compared with those generated in the lowland (Shanghai, China) and various global regions.

Methods
20mSRT performance (number of completed laps) and predicted peak oxygen consumption (VO2peak) were used as indicators of CRF. We measured the CRF of 1,717 healthy children and adolescents aged 9–18 years living in Tibet. The CRF data from school-age subjects in Shanghai (2,437 boys and 2,396 girls) and worldwide (1,142,026 students from 50 countries/regions in Africa, Asia, Europe, Latin America, North America, and Oceania) were collated from published papers.

Results
The average CRF of the participants from Tibet was 39.8 mL/kg/min. The male subjects (n = 876; 41.1 ± 4.42 mL/kg/min) had a higher average CRF than their female counterparts (n = 841; 37.8 ± 5.40 mL/kg/min). CRF decreased with age in both sexes at statistical significance (F = 1249.9, p for trend 0.05). The indigenous Tibetans (n = 1289; 40.1 ± 3.71 mL/kg/min) had a significant higher average CRF than those of Han descent (n = 394; 38.9 ± 4.70 mL/kg/min) (p < 0.05).

Conclusions
Children and adolescents aged 7–18 years residing above 3,500 m in Tibet displayed lower CRF traits compared with their counterparts from the plains area and other high altitude places. CRF varied according to age, sex, and ethnic group. Given the importance of CRF in children and adolescents, effective intervention strategies should be implemented to improve CRF in children and adolescents on the plateau.
Managing risk in ski resorts: Environmental factors affecting actual and estimated speed on signposted groomed slopes in a cohort of adult recreational alpine skiers
Authors: Carus Luis , Castillo Isabel 
Published: August 2021

BackgroundCertain weather conditions are clearly harmful, increasing the risk of injury of winter sports participants substantially. The objective of this study was to investigate actual speeds of skiers on signposted groomed slopes and to measure their skill to accurately estimate them with regard to environmental conditions such as visibility, sky cover, snow quality, wind and temperature.MethodsThe data were obtained from a sample of 421 adult recreational skiers taking ski courses. The Pearson correlation coefficient was used to explore the relationship between actual and estimated speed for all participants. Multiple linear regression analysis was used to measure the effect of environmental conditions on both the skiers’ actual speeds and their errors of estimation. Values of 0.05 or less were considered to indicate statistical significance.ResultsThe Pearson correlation coefficient between estimated and actual speed was 0.90 (P < 0.001). Skiers underestimated their actual speed on average by 13.06 km/h or 24.1%. Visibility, quality of snow and wind speed were shown to significantly affect both actual maximum speed and estimated speed. Good visibility, grippy snow and calm wind were associated with both the highest actual maximum speed and the lowest ability to estimate it.ConclusionCertain environmental conditions are associated with the actual speed at which skiers travel and with their ability to estimate it. Visibility, quality of snow and wind speed seem to influence both actual speed and the ability to estimate it while sky cover and temperature do not. A reinforced understanding of skiing speed on signposted groomed slopes is useful to gain insight into crashes and the mechanisms of resulting injuries, to evaluate means of protection and to devise successful prevention policies in ski resorts.
Fluid resuscitation and outcomes in heart failure patients with severe sepsis or septic shock: A retrospective case-control study
Authors: Acharya Roshan , Patel Aakash , Schultz Evan , Bourgeois Michael , Kandinata Natalie , Paswan Rishi , Kafle Smita , Sedhai Yub Raj , Younus Usman 
Published: August 2021

BackgroundThe use of ≥30 mL/Kg fluid bolus in congestive heart failure (CHF) patients presenting with severe sepsis or septic shock remained controversial due to the paucity of data.MethodsThe retrospective case-control study included 671 adult patients who presented to the emergency department of a tertiary care hospital from January 01, 2017 to December 31, 2019 with severe sepsis or septic shock. Patients were categorized into the CHF group and the non-CHF group. The primary outcome was to evaluate the compliance with ≥30 mL/Kg fluid bolus within 6 hours of presentation. The comparison of baseline characteristics and secondary outcomes were done between the groups who received ≥30 mL/Kg fluid bolus. For the subgroup analysis of the CHF group, it was divided based on if they received ≥30 mL/Kg fluid bolus or not, and comparison was done for baseline characteristics and secondary outcomes. Univariate and multivariable analyses were performed to explore the differences between the groups for in-hospital mortality and mechanical ventilation.ResultsThe use of ≥30 mL/Kg fluid bolus was low in both the CHF and non-CHF groups [39% vs. 66% (p<0.05)]. Mortality was higher in the CHF group [33% vs 18% (p<0.05)]. Multivariable analysis revealed that the use of ≥30 mL/Kg fluid bolus decreased the chances of mortality by 12% [OR 0.88, 95% CI 0.82–0.95 (p<0.05)]. The use of ≥30 mL/Kg fluid bolus did not increase the odds of mechanical ventilation [OR 0.99, 95% CI 0.93–1.05 (p = 0.78)]. In subgroup analysis, the use of ≥30 mL/Kg fluid bolus decreased the chances of mortality by 5% [OR 0.95, 95% CI 0.90–0.99, (p<0.05)] and did not increase the odds of mechanical ventilation. The presence of the low ejection fraction did not influence the chance of getting fluid bolus.ConclusionThe use of ≥30 mL/Kg fluid bolus seems to confer protection against in-hospital mortality and is not associated with increased chances of mechanical ventilation in heart failure patients presenting with severe sepsis or septic shock.
Estimation of benzathine penicillin G demand for congenital syphilis elimination with adoption of dual HIV/syphilis rapid diagnostic tests in eleven high burden countries
Authors: Shah Sapan , Garg Surbhi , Heath Katherine , Ofili Obiageli , Bansal Yashika , Seghers Frederic , Storey Andrew , Taylor Melanie 
Published: August 2021

Background
WHO recommends use of rapid dual HIV/syphilis tests for screening pregnant women (PW) during antenatal care to prevent mother-to-child transmission. Scale-up of testing implies a need to accurately forecast and procure benzathine penicillin (BPG) to treat the additionally identified PW with syphilis.

Methods
Country-reported ANC coverage, PW syphilis screening and treatment coverage values in 2019 were scaled linearly to EMTCT targets by 2030 (constant increasing slope from 2019 figures to 95% in 2030) for 11 focus countries. Antenatal syphilis screening coverage was substituted with HIV screening coverage to estimate potential contribution of rapid dual HIV/syphilis tests in identifying additional PW with syphilis. BPG demand was calculated for 2019–2030 accordingly.

Results
The estimated demand for BPG (in 2.4 million unit vials) using current maternal syphilis prevalence and treatment coverage will increase from a baseline of 414,459 doses in 2019 to 683,067 doses (+65%) in 2021 assuming immediate replacement of single HIV test kits with rapid dual HIV/syphilis tests for these 11 countries. Continued scale up of syphilis screening and treatment coverage to reach elimination coverage of 95% will result in an estimated demand increase of 160%, (663,969 doses) from 2019 baseline for a total demand of 1,078,428 BPG doses by 2030.

Conclusions
Demand for BPG will increase following adoption of rapid dual HIV/syphilis test kits due to increases in maternal diagnoses of syphilis. To eliminate congenital syphilis, MNCH clinical programs will need to synergize with disease surveillance programs to accurately forecast BPG demand with scale up of antenatal syphilis screening to ensure adequate treatment is available for pregnant women diagnosed with syphilis.