bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of survival distributions in clinical trials: A practical guidance
Authors: Chen Xiaotian , Wang Xin , Chen Kun , Zheng Yeya , Chappell Richard J , Dey Jyotirmoy 
Published: June 2020

Background In randomized clinical trials with censored time-to-event outcomes, the logrank test is known to have substantial statistical power under the proportional hazards assumption and is widely adopted as a tool to compare two survival distributions. However, the proportional hazards assumption is impossible to validate in practice until the data are unblinded. However, the statistical analysis plan of a randomized clinical trial and in particular its primary analysis method must be pre-specified before any unblinded information may be reviewed. Purpose The purpose of this article is to guide applied biostatisticians in the prespecification of a desired primary analysis method when a treatment effect with nonproportional hazards is anticipated. While articles proposing alternate statistical tests are aplenty, to the best of our knowledge, there is no article available that attempts to simplify the choice and prespecification of a primary statistical test under specific expected patterns on nonproportional hazards. We provide such guidance by reviewing various tests proposed as more powerful alternatives to the standard logrank test under nonproportional hazards and simultaneously comparing their performance under a wide variety of nonproportional hazards scenarios to elucidate their advantages and disadvantages. Method In order to select the most preferable test for detecting specific differences between survival distributions of interest while controlling false positive rates, we review and assess the performance of weighted and adaptively weighted logrank tests, weighted and adaptively weighted Kaplan–Meier tests and versatile tests under various patterns of nonproportional hazards treatment effects through simulation. Conclusion We validate some of the claimed properties of the proposed extensions and identify tests that may be more preferable under specific expected pattern of nonproportional hazards when such knowledge is available. We show that versatile tests, while achieving robustness to departures from proportional hazards, may lose interpretation of directionality (superiority or inferiority) and can only be seen to test departures from equality. Detailed summary and discussion of the performance of each test in terms of type I error rate and power are provided to formulate specific guidance about their applicability and use.
Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versusHER2-directed therapies
Authors: Zhou Jiebai , Ding Ning , Xu Xiaobo , Zhang Yong , Ye Maosong , Li Chun , Hu Jie 
Published: June 2020

Background: Lung cancer is now the leading cause of cancer mortality worldwide for both men and women. In non-small cell lung cancer (NSCLC), matching a specifically targeted drug to the identified driver mutation in each patient resulted in dramatically improved therapeutic efficacy, often in conjunction with decreased toxicity. Mutations in HER2 have been identified as an oncogenic driver gene for NSCLC. This retrospective study was conducted to better understand the clinical outcomes of advanced lung cancer patients harboring HER2 mutations treated with chemotherapies and HER2-targeted agents, as well as the optimal clinical choice. Methods: Patients who were diagnosed with advanced lung cancer (stage IIIB/IV) and had undergone molecular testing at Zhongshan Hospital, Fudan University, Shanghai, China from April 2016 to December 2018 were reviewed. For patients that had HER2 mutant advanced lung cancer, we analyzed their clinical and molecular features and clinical outcomes, including overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and objective response rate (ORR). Results: We identified 44 patients harboring HER2 mutations. Their median age was 56 years, with the majority being women ( n = 24), never smokers ( n = 32), and having the adenocarcinoma genotype ( n = 42). Amongst the HER2 mutations present, a 12 base pair in-frame insertion in exon 20 with p.771insAYVM was the most common subtype in patients with known detail variants of HER2 mutation (9/27). The median OS from the date of advanced disease diagnosis was 9.9 months with 24 deaths, and a median follow-up of 12.7 months for survivors. For patients with a known HER2 exon 20 insertion mutation, OS tended to be superior (though not statistically) in the first-line HER2-TKI group to that in the group receiving chemotherapy (10.8 versus 9.8 months, p = 0.40). However, patients that received first-line chemotherapy had a median PFS of 5.9 months, numerically longer than that of the HER2-TKI group (4.6 months, p = 0.63). Patients who received HER2-targeted therapy as first-line therapy had an improved OS (10.8 versus 10.1 months, p = 0.30) and PFS (4.6 versus 2.8 months, p = 0.36) relative to those who received HER2-targeted therapy as subsequent-line therapy, although they did not meet the threshold for statistical significance. Furthermore, patients with AYVM mutation were associated with poor clinical outcomes. Conclusion: Pemetrexed-based chemotherapy remains an important component of care for patients with HER2-mutant NSCLC. HER2-TKI given as an initial therapy may bring more clinical benefits than when given as a subsequent-line therapy. Refining the patient population based on patterns of HER2 variants may help improve the efficacy of anti- HER2 treatment in lung cancer. Developing highly effective and tolerable HER2-targeted agents is urgently needed for this population.
Acute Effects of Weighted Baseball Throwing Programs on Shoulder Range of Motion
Authors: Reinold Michael M. , Macrina Leonard C. , Fleisig Glenn S. , Drogosz Monika , Andrews James R. 
Published: June 2020

Background: Baseball pitching injuries are increasing at an alarming rate. While weighted ball throwing programs may be effective at increasing pitching velocity, previous research has identified a 24% injury rate and a 3.3° increase in shoulder external rotation (ER) range of motion (ROM) after performing a 6-week program. However, previous research has not investigated, separately, the immediate effects of throwing underloaded and overloaded balls on ROM. The purpose of this study was to examine the acute effects of throwing differently weighted baseballs on shoulder ROM. By analyzing these differences, it may be possible to determine the specific weight range that may lead to the greatest increase in ROM and potential injury risk. Hypothesis: Throwing with weighted balls will result in an increase in shoulder ER ROM. Study Design: Randomized controlled trial. Level of Evidence: Level 2. Methods: A total of 16 male high school baseball pitchers agreed to participate in this study. The participants were (mean ± SD) 17.1 ± 1.0 years of age, 1.81 ± 0.09 m tall, and had a mass of 79.2 ± 11.1 kg. Each participant was tested on 3 different days, 1 week apart, with 3 different conditions in random order: (1) underload throwing, using regulation 5-oz baseballs and 4- and 2-oz balls; (2) overload throwing, using 5-, 6-, and 9-oz balls; and (3) extreme overload throwing, using 5-, 16-, and 32-oz balls. Each testing session began by measuring passive shoulder ROM (external rotation and internal rotation) using standard goniometric measurements. Participants then performed 3 throws with each weighted ball from 3 different positions (kneeling, rocker, and run-and-gun) for a total of 27 throws each test session. ROM measurements were repeated at the end of each test session. The effect of each throwing condition on ROM was compared from pre- to posttraining using a paired t test ( P ≤ 0.05). Results: There was no significant difference in ER after throwing at underloaded weights. The overload condition showed a statistically significant increase of 3.3° in external rotation ( P = 0.05). The extreme overload condition showed a statistically significant increase in ER of 8.4° ( P < 0.001). There were no differences in internal rotation for any group. Conclusion: A significant increase in shoulder ER was observed immediately after throwing overload weighted balls. This effect increased as the weights of the balls increased. Clinical Relevance: Throwing with overload weighted baseballs causes an immediate increase in shoulder ER ROM. It is unknown why these changes occur; however, the results may explain both the increase in velocity and injury rates previously observed from throwing weighted balls. The current study results may be used to develop more scientifically validated weighted ball programs. Heavier balls should be used with caution, and ROM should be monitored during implementation of these programs.
Two cases of immunoglobulin G4 (IgG4)-related hypophysitis diagnosed without pituitary biopsy
Authors: Ma Wanlu , Wang Xi , Nie Min , Fu Junling , Mao Jiangfeng , Wu Xueyan 
Published: June 2020

Background: Immunoglobulin G4-related hypophysitis (IgG4-RH) is a rare disease, diagnosis of which typically depends on histopathology following an invasive pituitary biopsy, possibly leading to permanent hypopituitarism. Herein, we report two cases of IgG4-RH with favorable responses to glucocorticoids. One of them was multiple organs involved and treated with glucocorticoids and methotrexate. Methods: We retrospectively review clinical features, radiological images, and treatment of two cases with IgG4-RH. In addition, literature on IgG4-RH was comprehensively reviewed and a new therapeutic strategy for IgG4-RH was provided. Results: A 45-year-old man presented with diabetes insipidus for 6 months. Pituitary magnetic resonance imaging (MRI) indicated thickening of pituitary stalk. His serum IgG4 was 13,500 mg/l and hormonal evaluation revealed isolated growth hormone deficiency. Pituitary biopsy was denied by the patient due to fears of permanent pituitary damage. Treatment with prednisone and methotrexate (MTX) for 1 week led to improvement in sellar images and reduction in IgG4 level. His IGF1 (insulin-like growth factor-1) recovered after a 4-month treatment. The second case is a 43-year-old woman presenting with diabetes insipidus and amenorrhea for 20 months. Her pituitary MRI was similar to the patient above. Her serum IgG4 level was 5980 mg/l and hormonal measurement confirmed isolated hypogonadotropic hypogonadism. After 2 weeks of prednisone, the sellar images improved. After 3 months of treatment, her pituitary MRI was normal, IgG4 level had decreased to near normal range, and menstruation resumed. Literature review found additional patients with IgG4-RH, who were treated successfully without invasive pituitary biopsy in a manner similar to our cases. Therefore, we discuss the necessity of invasive pituitary biopsy for IgG4-RH. Conclusion: For suspected IgG4-RH with pituitary hormone deficiency, biopsy-induced hypopituitarism may be avoided by using diagnostic glucocorticoid treatment. Impaired pituitary hormone secretion may be recovered in response to steroid therapy. Improved pituitary MRI after 1–2 weeks of glucocorticoid treatment may provide diagnostic evidence of IgG4-RH.
Intellectual property rights in the EU pre-commercial procurement for innovation
Authors: Dimitri Nicola 
Published: June 2020

In 2007 the EC introduced pre-commercial procurement (PCP) to endow the EU public sector with a legal instrument for procuring innovative solutions, unavailable in the market. To induce firms to participate in a PCP, the EC suggests contracting authorities to leave the intellectual property rights (IPR) of the new solution with the firms. Based on the perspective of a possible commercial success, the IPR should work as a major incentive for companies to engage in a PCP. As important as the EC seems to consider the IPR, for a successful PCP, so far no guidelines have been provided on how to estimate their economic value. This paper proposes a methodology for such evaluation, discussing its advantages and limitations. A main message of the paper is that IPR economic value should be based on the expected profits coming from commercialisation of the would-be innovative solution. Moreover, the value should change across the different development phases of the PCP. The findings could be useful for a broad audience of PCP potential participants, contracting authorities intending to promote a PCP and third parties interested in buying the IPR.
In vitro and in vivo anti-inflammatory properties of Mayan propolis
Authors: Xool-Tamayo Jorge , Chan-Zapata Ivan , Arana-Argaez Víctor Ermilo , Villa-de la Torre Fabiola , Torres-Romero Julio César , Araujo-Leon Jesus Alfredo , Aguilar-Ayala Fernando J , Rejón-Peraza Marina E , Castro-Linares Nelly C , Vargas-Coronado Rossana F , Cauich-Rodríguez Juan V 
Published: June 2020

Introduction Propolis has been used traditionally for different human diseases and even recently as dental biomaterials because of its antibacterial, antimycotic, and anti-inflammatory properties. However, a proper correlation between in vitro and in vivo anti-inflammatory properties has not been clearly established. Methods The composition of propolis was determined by high-performance liquid chromatography–ultraviolet mass spectrometry (HPLC-UV-MS). Viability of ethanolic propolis solution was evaluated by thiazolyl blue tetrazolium bromide (MTT) assay on murine macrophages. The anti-inflammatory properties were assessed both in vitro through the enzyme-linked immunosorbent assay (ELISA) quantification of various cytokines and in vivo by induced edemas. Results Chemical analysis showed pinocembrin, pinobanksin-3-O-acetate, and pinobanksin-3-O-propionate as the main components of propolis. Macrophage viability was high (106%) when propolis was used up to 50 µg/mL. ELISA studies showed a reduction in the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) up to 145 pg/mL, 350 pg/mL, and 210 pg/mL, respectively, while the anti-inflammatory cytokines (IL-10 and IL-4) were increased up to 833 pg/mL and 446 pg/mL. Finally, edema was reduced on paw and ear mice by 9% and 22%, respectively. Conclusion Mayan propolis has strong in vitro anti-inflammatory properties without compromising macrophage viability, resulting in a low-to-mild in vivo anti-inflammatory response.
The hidden complexity of measuring number of chronic conditions using administrative and self-report data: A short report
Authors: Griffith Lauren E , Gruneir Andrea , Fisher Kathryn A , Upshur Ross , Patterson Christopher , Perez Richard , Favotto Lindsay , Markle-Reid Maureen , Ploeg Jenny 
Published: June 2020

Objective:To examine agreement between administrative and self-reported data on the number of and constituent chronic conditions (CCs) used to measure multimorbidity.Study Design and Setting:Cross-sectional self-reported survey data from four Canadian Community Health Survey waves were linked to administrative data for residents of Ontario, Canada. Agreement for each of 12 CCs was assessed using kappa ( κ) statistics. For the overall number of CCs, perfect agreement was defined as agreement on both the number and constituent CCs. Jackknife methods were used to assess the impact of individual CCs on perfect agreement.Results:The level of chance-adjusted agreement between self-report and administrative data for individual CCs varied widely, from κ = 5.5% (inflammatory bowel disease) to κ = 77.5% (diabetes), and there was no clear pattern on whether using administrative data or self-reported data led to higher prevalence estimates. Only 26.9% of participants had perfect agreement on the number and constituent CCs; 10.6% agreed on the number but not constituent CCs. The impact of each CC on perfect agreement depended on both the level of agreement and the prevalence of the individual CC.Conclusion:Our results show that measuring agreement on multimorbidity is more complex than for individual CCs and that even small levels of individual condition disagreement can have a large impact on the agreement on the number of CCs.
The Ophthalmology Chief Resident: Does Surgical Volume Correlate With Likelihood of Selection?
Authors: Richards Nikisha Q , Osardu Reginald K 
Published: June 2020

Purpose: Investigate whether number of logged Accreditation Council for Graduate Medical Education (ACGME) surgical cases correlates with likelihood of Virginia Commonwealth University Health System (VCUHS) ophthalmology residents being selected as the chief resident. Design: Retrospective study. Participants: VCUHS ophthalmology residents from 2006 to 2016. Methods: Analyze association between chief resident selection and logged cases. Main outcome measures: Review number of archived logged ACGME surgical cases of all residents between the years 2006 and 2017. Review chief resident selected each year 2006-2016. Results: Our analysis correctly predicted the chief resident in 2 of the 10 years analyzed. Conclusion: Those residents performing the most surgical procedures in each respective class were not more likely to be selected as chief resident.
Risk factors for women’s non-utilization of decentralized primary health care facilities for postnatal care in rural western Ethiopia
Authors: Tolera Habtamu , Gebre-Egziabher Tegegne , Kloos Helmut 
Published: June 2020

Objective: Evidence suggests postnatal care contributes to reductions in maternal mortality. In Ethiopia, the proportion of women who do not utilize postnatal care after birth is high and the frequency of postnatal checks falls short of the four visits recommended by World Health Organization. This study examined risk factors associated with non-utilization of decentralized local health facilities, namely, health posts, health centers, and a primary hospital, for postnatal care services in Gida Ayana Woreda in rural western Ethiopia. Methods: In this study, 454 mothers were examined for the following risk factors: kebele (the smallest administrative unit in Ethiopia) in which decentralized health care facilities were located, postnatal woman’s age, antenatal care service visit, experience of postnatal complications, knowledge of postnatal complications, knowledge of the recommended number of postnatal care visits, knowledge of the availability/provision of postnatal care, and health extension workers’ home visits. Bivariate and multivariable logistic regression analyses were applied to identify predictors of non-utilization of decentralized local facilities for postnatal care services. Results: Over half (55.7%) of the women did not utilize postnatal care within 42 days of delivery, and only 10.0% utilized the care considered appropriate according to World Health Organization guidelines. After adjusting for various potential confounding factors, we found the following risks to be strongly associated with non-utilization of decentralized health care facilities for postnatal care services: some outer rural administrative decentralization entities such as Angar, Lalistu, and Ejere kebeles; age 35 years or older (adjusted odds ratio = 3.4, 95% confidence interval: 1.4–8.3), not receiving antenatal care during this pregnancy (adjusted odds ratio = 2.0, 95% confidence interval: 1.1–3.7), no experience of any postnatal complications (adjusted odds ratio = 3.3, 95% confidence interval: 1.7–6.4), and no knowledge of at least one postnatal complication (adjusted odds ratio = 2.0, 95% confidence interval: 1.2–3.3). Risk factors highly but less strongly associated with women’s non-utilization of postnatal care services were no knowledge of the standard number of postnatal care visits recommended, no knowledge about the availability/provision of services at a local health facility, and no home visit from health extension worker by day 3 post-delivery. Conclusion: The risk factors for women’s non-utilization of decentralized health care facilities for postnatal care identified in this study need to be considered in interventions for enhancing the utilization of the service and reducing maternal and newborn deaths in rural western Ethiopia. Strengthening of postnatal care services, especially in the more remote kebeles, should include upgrading of the referral system and expansion of counseling of women by health extension workers.
How I treat relapsed acute lymphoblastic leukemia in the pediatric population
Authors: Hunger Stephen P. , Raetz Elizabeth A. 
Published: June 2020

AbstractRelapsed acute lymphoblastic leukemia (ALL) has remained challenging to treat in children, with survival rates lagging well behind those observed at initial diagnosis. Although there have been some improvements in outcomes over the past few decades, only ∼50% of children with first relapse of ALL survive long term, and outcomes are much worse with second or later relapses. Recurrences that occur within 3 years of diagnosis and any T-ALL relapses are particularly difficult to salvage. Until recently, treatment options were limited to intensive cytotoxic chemotherapy with or without site-directed radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). In the past decade, several promising immunotherapeutics have been developed, changing the treatment landscape for children with relapsed ALL. Current research in this field is focusing on how to best incorporate immunotherapeutics into salvage regimens and investigate long-term survival and side effects, and when these might replace HSCT. As more knowledge is gained about the biology of relapse through comprehensive genomic profiling, incorporation of molecularly targeted therapies is another area of active investigation. These advances in treatment offer real promise for less toxic and more effective therapy for children with relapsed ALL, and we present several cases highlighting contemporary treatment decision-making.
High-flow nasal cannula improves clinical efficacy of airway management in patients undergoing awake craniotomy
Authors: Yi Ping , Li Qiong , Yang Zhoujing , Cao Li , Hu Xiaobing , Gu Huahua 
Published: June 2020

AbstractBackgroundAwake craniotomy requires specific sedation procedure in an awake patient who should be able to cooperate during the intraoperative neurological assessment. Currently, limited number of literatures on the application of high-flow nasal cannula (HFNC) in the anesthetic management for awake craniotomy has been reported. Hence, we carried out a prospective study to assess the safety and efficacy of humidified high-flow nasal cannula (HFNC) airway management in the patients undergoing awake craniotomy.MethodsSixty-five patients who underwent awake craniotomy were randomly assigned to use HFNC with oxygen flow rate at 40 L/min or 60 L/min, or nasopharynx airway (NPA) device in the anesthetic management. Data regarding airway management, intraoperative blood gas analysis, intracranial pressure, gastric antral volume, and adverse events were collected and analyzed.ResultsPatients using HFNC with oxygen flow rate at 40 or 60 L/min presented less airway obstruction and injuries. Patients with HFNC 60 L/min maintained longer awake time than the patients with NPA. While the intraoperative PaO2and SPO2were not significantly different between the HFNC and NPA groups, HFNC patients achieved higher PaO2/FiO2than patients with NPA. There were no differences in Brain Relaxation Score and gastric antral volume among the three groups as well as before and after operation in any of the three groups.ConclusionHFNC was safe and effective for the patients during awake craniotomy.Trial registrationChinese Clinical Trial Registry,CHiCTR1800016621. Date of Registration: 12 June 2018.