bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence of EGCG on the Pharmacokinetics and Pharmacodynamics of Bisoprolol and a New Method for Simultaneous Determination of EGCG and Bisoprolol in Rat Plasma
Authors: Zeng Weiwei , Lao Sixian , Guo Yi , Wu Yufeng , Huang Min , Tomlinson Brian , Zhong Guoping 
Published: May 2022

Background and AimResearch has shown that green tea catechins may influence the activity of drug metabolizing enzymes and drug transporters. We examined whether epigallocatechin-3-gallate (EGCG) affected the pharmacokinetics and pharmacodynamics of bisoprolol in rats.MethodsA sensitive, specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established for the quantitative determination of EGCG and bisoprolol. The pharmacokinetic parameters of EGCG and bisoprolol in Sprague-Dawley (SD) rats were analyzed using non-compartmental methods with the aid of the computer program WinNolin. Blood pressure (BP) of spontaneously hypertensive rats (SHRs) was monitored by the tail-cuff method. Bisoprolol was given as single doses of 10 mg/kg with or without EGCG 100 mg/kg by gavage or by intravenous injection.ResultsIntake of EGCG with bisoprolol by gavage significantly reduced the Cmax (mean Cmax from 2012.31 to 942.26 ng/mL, P &lt; 0.05) and increased the Tmax (mean Tmax from 0.5 to 0.83 h, P &lt; 0.01) for bisoprolol. After intravenous injection, EGCG significantly increased the apparent volume of distribution of bisoprolol (mean Vz/F from 1629.62 to 2473.27 mL/Kg, P &lt; 0.05) and tended to increase the clearance. The absolute bioavailability of bisoprolol was reduced from 92.04 to 66.05% in rats when bisoprolol was administered with EGCG. Heart rate reduction was less in SHRs when EGCG was given by gavage with bisoprolol whereas BP reduction occurred more rapidly.ConclusionThis study showed that the simultaneous administration of EGCG by gavage at a dose of 100 mg/kg was associated with decreased Cmax and increased Tmax of bisoprolol, and the Vz/F of bisoprolol was increased when administered with EGCG by intravenous injection in SD rats. Moreover, the early heart rate reduction with bisoprolol was attenuated and BP reduction occurred earlier when EGCG was given with bisoprolol by gavage in SHRs.
Impact of Introducing Intensity Modulated Radiotherapy on Curative Intent Radiotherapy and Survival for Lung Cancer
Authors: Fornacon-Wood Isabella , Chan Clara , Bayman Neil , Banfill Kathryn , Coote Joanna , Garbett Alex , Harris Margaret , Hudson Andrew , Kennedy Jason , Pemberton Laura , Salem Ahmed , Sheikh Hamid , Whitehurst Philip , Woolf David , Price Gareth , Faivre-Finn Corinne 
Published: May 2022

BackgroundLung cancer survival remains poor. The introduction of Intensity-Modulated Radiotherapy (IMRT) allows treatment of more complex tumours as it improves conformity around the tumour and greater normal tissue sparing. However, there is limited evidence assessing the clinical impact of IMRT. In this study, we evaluated whether the introduction of IMRT had an influence on the proportion of patients treated with curative-intent radiotherapy over time, and whether this had an effect on patient survival.Materials and MethodsPatients treated with thoracic radiotherapy at our institute between 2005 and 2020 were retrospectively identified and grouped into three time periods: A) 2005-2008 (pre-IMRT), B) 2009-2012 (selective use of IMRT), and C) 2013-2020 (full access to IMRT). Data on performance status (PS), stage, age, gross tumour volume (GTV), planning target volume (PTV) and survival were collected. The proportion of patients treated with a curative dose between these periods was compared. Multivariable survival models were fitted to evaluate the hazard for patients treated in each time period, adjusting for PS, stage, age and tumour volume.Results12,499 patients were included in the analysis (n=2675 (A), n=3127 (B), and n=6697 (C)). The proportion of patients treated with curative-intent radiotherapy increased between the 3 time periods, from 38.1% to 50.2% to 65.6% (p&lt;0.001). When stage IV patients were excluded, this increased to 40.1% to 58.1% to 82.9% (p&lt;0.001). This trend was seen across all PS and stages. The GTV size increased across the time periods and PTV size decreased. Patients treated with curative-intent during period C had a survival improvement compared to time period A when adjusting for clinical variables (HR=0.725 (0.632-0.831), p&lt;0.001).ConclusionIMRT was associated with to more patients receiving curative-intent radiotherapy. In addition, it facilitated the treatment of larger tumours that historically would have been treated palliatively. Despite treating larger, more complex tumours with curative-intent, a survival benefit was seen for patients treated when full access to IMRT was available (2013-2020). This study highlights the impact of IMRT on thoracic oncology practice, accepting that improved survival may also be attributed to a number of other contributing factors, including improvements in staging, other technological radiotherapy advances and changes to systemic treatment.
Absence of PSA Flare With Apalutamide Administered 1 Hour in Advance With GnRH Agonists: Case Report
Authors: Hu Zhiquan , Liu Zhenghao , Chen Zhiyuan , Zeng Xing , Wang Zhihua , Yang Chunguang 
Published: May 2022

ObjectiveTo examine the effects of apalutamide on endocrine function and flare prevention in metastatic hormone-sensitive prostate cancer (mHSPC) patients administered GnRH agonists.MethodsThe first newly diagnosed mHSPC patient took apalutamide for 2 weeks followed by combination with GnRH agonist, as recommended by clinical guidelines. Serum luteinizing hormone (LH), testosterone, and PSA were detected during the oral administration of apalutamide before and after ADT. Eight newly diagnosed mHSPC patients innovatively took apalutamide 1 hour before GnRH agonist administration; LH, testosterone and PSA were detected before and after ADT.ResultsIn the first patient, LH and testosterone levels were increased during apalutamide monotherapy, and serum PSA levels decreased rapidly, demonstrating apalutamide effectively blocked AR signaling. In patients on the 1-hour regimen, combined treatment with apalutamide and GnRH agonists led to peak level of testosterone on day 3 and castration level on day 28, while PSA decreased continuously. No one experienced dysuria or bone pain worsen after ADT.ConclusionTaking apalutamide 1 hour in advance may effectively prevent the flare-up effect in prostate cancer patients treated with GnRH agonists. Compared with the 2-week regimen, the 1-hour regimen could simplify the treatment process and bring testosterone to castration levels in advance.
Efficacy and Safety Profile of Histone Deacetylase Inhibitors for Metastatic Breast Cancer: A Meta-Analysis
Authors: Wang Changjun , Lin Yan , Zhu Hanjiang , Zhou Yidong , Mao Feng , Huang Xin , Sun Qiang , Li Chenggang 
Published: May 2022

IntroductionAcquired resistance to endocrine therapy (ET) remains a big challenge in the management of metastatic breast cancer (MBC). A novel therapeutic agent, histone deacetylase inhibitors (HDACi), targets the abnormal epigenetic modification and may overcome acquired resistance. However, HDACi efficacy and the safety profile for hormone receptor (HoR)-positive/human epidermal growth factor receptor 2 (HER2)-negative MBC remain controversial.MethodsTwo independent reviewers searched PubMed, Embase, and Cochrane Central Register of Controlled Trials databases for relevant studies on HDACi and HoR+/HER2- MBC. Demographic and clinicopathological parameters were extracted and presented as means and proportions, and between-group differences were assessed by Pearson chi-square test. Fixed- or random-effects models were used for meta-analysis based on inter-study heterogeneity. Pooled results were presented as L’Abbé plot and forest plot. Funnel plot and Egger’s test were employed for evaluation of publication bias.ResultsFour studies with 1,457 patients were included for meta-analysis. The overall objective response rates (ORRs) of HDACi + ET (HE) and placebo + ET (PE) groups were 11.52% and 6.67%, respectively. The HE regimen significantly increased ORR (odds ratio [OR] 1.633, 95% confidence interval [CI] = 1.103–2.418, p &lt; 0.05) and showed higher clinical benefit rate (CBR) than the PE regimen (HE vs. PE groups: 38.82% vs. 30.58%, OR 1.378, 95% CI = 1.020–1.861, p &lt; 0.05). Additionally, the HE regimen was associated with prolonged progression-free survival (PFS) (hazard ratio [HR] 0.761, 95% CI = 0.650–0.872, p &lt; 0.001) and overall survival (OS) (HR 0.849, 95% CI = 0.702–0.996, p &lt; 0.001). Regarding safety profile, the HE regimen had increasing toxicity in terms of higher overall adverse event (AE), Grade ≥3 AE, dose modification, and discontinuation rate.ConclusionsThis meta-analysis validated that the HE regimen had superior efficacy over control in terms of ORR, CBR, PFS, and OS, but was accompanied with increasing toxicity. HDACi plus ET could serve as an important option in managing HoR+/HER2- MBC. Future studies may focus on the clinical difference among different HDACi and AE managements to enhance tolerability.
A Pilot Study to Assess Opportunistic Use of CT-Scan for Osteoporosis Screening in Chronic Pancreatitis
Authors: McNabb-Baltar Julia , Manickavasagan Hanisha R. , Conwell Darwin L. , Lu Andrew , Yadav Dhiraj , Hart Philip A. , Lara Luis F. , Cruz-Monserrate Zobeida , Ing Steven , Hinton Alice , Mace Thomas A. , Bradley David , Shah Zarine K. 
Published: May 2022

Objectives: CT scans are commonly performed in patients with chronic pancreatitis (CP). Osteopathy and fractures are recognized in CP but no osteoporosis screening guidelines are recommended. “Opportunistic” CT scan-derived bone density thresholds are assessed for identifying osteoporosis in CP.Methods: Retrospective pilot cohort study. CP subjects who had CT scans and dual-energy x-ray absorptiometry (DXA) within 1 year were included. CT-derived bone density was measured at the L1 level. Pearson’s correlation was performed between age and CT-derived bone density in Hounsfield unit (HU). Univariate analysis using HU to identify osteoporosis was performed at various thresholds of bone density. The discriminatory ability of the model was evaluated with the area under the receiver operating characteristic (ROC) curve (AUC). Several HU thresholds were tested.Results: Twenty-seven CP subjects were included, of whom 11 had normal bone density, 12 osteopenia, and four osteoporosis on DXA. The mean age was 59.9 years (SD 13.0). There was a negative correlation of age with HU (r = −0.519, p = 0.006). CT-derived bone density predicted DXA-based osteoporosis in the univariable analysis (Odds Ratio (OR) = 0.97 95% Confidence Interval (CI) 0.94–1.00, p = 0.03). HU thresholds were tested. A threshold of 106 HU maximized the accuracy (AUC of 0.870).Conclusions: CT scan may be repurposed for “opportunistic” screening to rule out osteoporosis in CP. A larger study is warranted to confirm these results.
How Egg Storage Duration Prior to Incubation Impairs Egg Quality and Chicken Embryonic Development: Contribution of Imaging Technologies
Authors: Adriaensen Hans , Parasote Vanille , Castilla Ines , Bernardet Nelly , Halgrain Maeva , Lecompte François , Réhault-Godbert Sophie 
Published: May 2022

Storing fertilised eggs prior to incubation is a frequent practice in commercial hatcheries to coordinate activities and synchronise hatchings. However, the conditions used to store eggs can have major impacts on egg quality and the subsequent viability of chicken embryos. While storage temperatures of 16–18°C are classically used in hatcheries, the duration of storage varies from three to more than 10 days. We explored the effect of storage duration (zero, three or 10 days; D0, D3 and D10, respectively) at 16°C, 80% relative humidity (RH) on egg quality (Broiler, Ross 308), using computed tomography (CT) and classical measurements (egg weight, eggshell strength, egg white pH, Haugh units, yolk index and colour). The results revealed that a storage duration of up to 10 days negatively affected some egg quality traits (yolk index and volume, air chamber volume and egg white pH). Eggs stored for three or 10 days were further incubated for 11, 13 or 15 days (37.8°C, 55% RH). Eggs were analysed by magnetic resonance imaging (MRI) and CT to assess the development of the embryo and internal egg changes occurring during incubation. First, data showed that the fertility and sex ratio of eggs were not affected by storage duration. However, the mortality of viable eggs was increased in the D10 group compared to the D3 group. Results of non-invasive imaging technologies revealed that the storage of eggs for 10 days impaired embryo growth as early as 11 days of incubation (decrease in brain and embryo volumes). Collectively, these data provide new evidence that the duration of egg storage negatively affects embryonic growth. They further corroborate that this parameter is likely to be crucial to synchronising embryonic stages and maybe reducing the hatching window, hence limiting the time spent by newborn chicks in hatchers. In addition, our results highlight that CT and MRI imaging technologies are useful non-invasive tools to evaluate egg quality prior to incubation and the impact of storage (or incubation) practices on developmental growth of the embryo.
Randomized Crossover Study of Auricular Plaster Therapy to Relieve Dental Anxiety in Children
Authors: Wang Jiangtao , Zhang Jie , Sun Dalei 
Published: May 2022

ObjectiveTo determine if auricular plaster therapy (APT) can alleviate dental anxiety in children aged 9 or 10 years old.MethodsA crossover research was conducted on children with at least two deep-arrested deciduous molar caries (N = 80?). The first group (N = 40) received APT intended to reduce anxiety prior to the first caries treatment, whereas the second group (N = 40) received placebo/control APT (no anticipated impact on anxiety). The APT approaches were exchanged after a washout period following the initial caries treatment. Additionally, both groups were also informed and given a demonstration regarding the procedures and equipment prior to their use as part of a Tell-Show-Do (TSD) protocol. The dentists, children, and parents were all involved in assessing the level of anxiety using general anxiety scales. Moreover, the average heart rate and salivary cortisol concentration, both of which are indications of anxiety, were compared between the pre- and post-intervention periods. The participants were unaware of the type of APT that was employed (anti-anxiety vs. control). To avoid inadvertently influencing the outcome, all psychologists, investigators, and data recorders were blinded to the randomized subject sequence.ResultsChildren treated with anti-anxiety APT demonstrated significantly higher levels of obedience than children treated with control APT (P &lt; 0.05). In addition, children treated with APT had a lower average heart rate while awaiting treatment, undergoing local anesthesia, and receiving dental caries treatment (P &lt; 0.05). These children had reduced salivary cortisol levels while awaiting treatment (P &lt; 0.05).ConclusionAnti-anxiety APT can help relieve dental anxiety in children.
The Association Between Adequate Prenatal Care and Severe Maternal Morbidity Among Teenage Pregnancies: A Population-Based Cohort Study
Authors: Nam Jin Young , Oh Sarah Soyeon , Park Eun-Cheol 
Published: May 2022

BackgroundThe aim of this study was to examine whether inadequate prenatal care affect the risk of severe maternal morbidity in teenage pregnancies.MethodsWe included 23,202 delivery cases among adolescent mothers aged between 13 and 19 years old with ≥ 37 weeks' gestational age. Data were derived from the National Health Insurance Service National Delivery Cohort in Korea between 2003 and 2018. We used a generalized estimating equation model while adjusting for numerous covariates to determine the adjusted relative risk (RR) associated with severe maternal morbidity. The main outcome measures were severe maternal morbidity and the Kessner Adequacy of Prenatal Care Index.ResultsSevere maternal morbidity occurred in 723 (3.1%) of the 23,202 investigated delivery cases. The risk of severe maternal morbidity was 1.8-fold higher among adolescent mothers who had received inadequate prenatal care (RR, 1.81, 95% confidence interval [CI], 1.39–2.37) and 1.6-fold higher among those who had received intermediate prenatal care (RR, 1.59, 95% CI, 1.33–1.87) compared to those with adequate prenatal care. Synergistic effects of inadequate prenatal care and maternal comorbidities affected severe maternal morbidity.ConclusionThis study confirmed that inadequate prenatal care is associated with increased risk of severe maternal morbidity among pregnant teenagers. Notably, maternal comorbidity and inadequate prenatal care produced synergistic effects on severe maternal morbidity. Public health policy makers should focus on the development and implementation of programs to ensure that adequate prenatal care and financial/healthcare support is provided to teenage mothers during their pregnancies.
Do Differences in Drinking Attitudes and Alcohol-Related Problems Explain Differences in Sick Leave? A Multilevel Analysis of 95 Work Units Within 14 Companies From the WIRUS Study
Authors: Hashemi Neda S. , Dalen Ingvild , Skogen Jens Christoffer , Sagvaag Hildegunn , Gimeno Ruiz de Porras David , Aas Randi Wågø 
Published: May 2022

BackgroundSystematic reviews have shown a strong relationship between alcohol consumption and sick leave. The effect of alcohol consumption on sick leave may, however, vary according to the work environment. While attitudes toward drinking may impact sick leave, there is little research on the contribution of drinking attitudes to sick leave. Moreover, alcohol-related problems and drinking attitudes may be influenced by the broader sociocultural contexts of the organizational units where people work.ObjectivesThis study aimed to explore the relationship of alcohol-related problems and drinking attitudes with sick leave while considering the nesting of employees within working units within companies.MethodData from the WIRUS (Workplace Interventions preventing Risky alcohol Use and Sick leave) study were linked to company-registered sick leave data for 2,560 employees from 95 different work units in public (n = 9) and private companies (n = 5) in Norway. Three-level (employee, work unit, and company) negative binomial regression models were estimated to explore the 12-month prospective association of alcohol-related problems and drinking attitudes with four measures of sick leave (one-day, short-term, long-term, and overall sick leave days). Models were adjusted for gender, age, cohabitation status, educational attainment, work position, and employment sector.ResultsWe observed higher variation of one-day, short-term, and overall sick leave days between companies than between work units within companies (15, 12, and 30% vs. 0, 5, and 8%, respectively). However, neither alcohol-related problems nor drinking attitudes were associated with sick leave and, thus, those variations in sick leave were not explained by alcohol-related problems or drinking attitudes.ConclusionOur findings suggest company-level differences are more important than within company differences when explaining differences in sick leave. While alcohol-related problems or drinking attitudes were not associated with sick leave, future studies may need to explore the role of company policies, practices, or social norms in variations in sick leave rates.
Fostering Resilient Health Systems in India: Providing Care for PLHIV Under the Shadow of COVID-19
Authors: Parikh Neha , Chaudhuri Angela , Syam Syama B. , Singh Pratishtha 
Published: May 2022

IntroductionThe novel coronavirus or COVID-19 has resulted in major human casualties, and extreme socio-economic crises causing catastrophic disturbances to health systems and communities alike. This study qualitatively explores the challenges experienced by healthcare providers while providing services to people living with HIV (PLHIV) during the pandemic outbreak and subsequent lockdown in India. The paper also explores strategies developed and adopted to provide continued care for PLHIV.MethodsUsing an empirical phenomenological approach, qualitative in-depth telephonic interviews were conducted with 19 HIV care providers from five states in India. The recorded interviews were transcribed and analyzed using inductive thematic analysis with the help of Dedoose software.ResultsFrom the analysis of participants' narratives, three main themes emerged: (1) Challenges of working during a pandemic; (2) Remodeling care delivery to ensure continuity of services; (3) Resilience.DiscussionOur findings highlight the challenges that providers faced, despite which, adaptive efforts were made to continue providing quality care for PLHIV through ingenious and innovative strategies. To foster resilient health systems, health workers are the primary stakeholders. We recommend formal social protection, comprehensive primary healthcare support, and sufficient capacity building for health workers for their self-care and pandemic preparedness.
A Cost-Effectiveness Analysis of Screening Strategies Involving Non-Invasive Prenatal Testing for Trisomy 21
Authors: Wang Shuxian , Liu Kejun , Yang Huixia , Ma Jingmei 
Published: May 2022

IntroductionIn accordance with social development, the proportion of advanced maternal age (AMA) increased and the cost of non-invasive prenatal testing (NIPT) decreased.ObjectiveWe aimed to investigate the benefits and cost-effectiveness of NIPT as primary or contingent strategies limited to the high-risk population of trisomy 21 (T21).MethodsReferring to parameters from publications or on-site verification, a theoretical model involving 1,000,000 single pregnancies was established. We presented five screening scenarios, primary NIPT (Strategy 1), contingent NIPT after traditional triple serum screening higher than 1/300 or 1/1,000 (Strategy 2-1 or 2-2), and age-based Strategy 3. Strategy 3 was stratified, with the following options: (1) for advanced maternal age (AMA) of 40 years and more, diagnostic testing was offered, (2) for AMA of 35–39 years, NIPT was introduced, (3) if younger than 35 years of age, contingent NIPT with risk higher than 1:300 (Strategy 3-1) or 1:1,000 (Strategy 3-2) will be offered. The primary outcome was an incremental cost analysis on the baseline and alternative assumptions, taking aging society, NIPT price, and compliance into consideration. The strategy was “appropriate” when the incremental cost was less than the cost of raising one T21 child (0.215 million US$). The second outcome included total cost, cost-effect, cost-benefit analysis, and screening efficiency.ResultsStrategy1 was costly, while detecting most T21. Strategy 2-1 reduced unnecessary prenatal diagnosis (PD) and was optimal in total cost, cost-effect, and cost-benefit analysis, nevertheless, T21 detection was the least. Strategy 3 induced most of the PD procedures. Then, setting Strategy2-1 as a baseline for incremental cost analysis, Strategy 3-1 was appropriate. In sensitivity analysis, when the NIPT price was lower than 47 US$, Strategy 1 was the most appropriate. In a society with more than 20% of people older than 35 years of age, the incremental cost of Strategy 3-2 was proper.ConclusionCombined strategies involving NIPT reduced unnecessary diagnostic tests. The AMA proportion and NIPT price played critical roles in the strategic decision. The age-based strategy was optimal in incremental cost analysis and was presented to be prominent as AMA proportion and NIPT acceptance increased. The primary NIPT was the most effective, but only at a certain price, it became the most cost-effective strategy.