bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis
Authors: Gen Soei , Tanaka Ichidai , Morise Masahiro , Koyama Junji , Kodama Yuta , Matsui Akira , Miyazawa Ayako , Hase Tetsunari , Hibino Yoshitaka , Yokoyama Toshihiko , Kimura Tomoki , Yoshida Norio , Sato Mitsuo , Hashimoto Naozumi 
Published: June 2022

Abstract
Background
Osimertinib—the third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)—has been widely used as a first-line treatment for patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib demonstrated central nervous system activity in patients with brain metastasis; however, its efficacy against other distant metastatic organs, including bone and liver, remains unclear. Therefore, we retrospectively analyzed the clinical efficacy of osimertinib in these patients in comparison to other EGFR-TKIs.

Methods
Clinical data of patients with advanced NSCLC receiving gefitinib/erlotinib (n = 183), afatinib (n = 55), or osimertinib (n = 150) at five medical institutions were retrospectively assessed for progression-free survival (PFS), overall survival (OS), and best overall response rate (ORR).

Results
In univariate and multivariate analyses, most distant metastases, including the brain and bone, were unrelated to the therapeutic efficacy of osimertinib, although liver metastasis and L858R mutation were independently associated with shorter PFS. PFS and OS in patients with liver metastases were significantly shorter than those in patients without liver metastases (PFS: 7.4 vs. 19.7 months, OS: 12.1 months vs. not reached, respectively). Osimertinib provided significantly longer PFS in patients with brain or bone metastasis and exon 19 deletion than the other EGFR-TKIs. The PFS of patients with liver metastases was not significantly different among the three EGFR-TKI groups. Furthermore, the ORR of osimertinib in patients with liver metastases was significantly attenuated, and the effectiveness was similar to 1st- or 2nd -generation EGFR-TKIs.

Conclusion
Osimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion; however, its efficacy against liver metastasis was remarkably attenuated. New therapeutic developments for patients with EGFR-mutant NSCLC with liver metastases are needed.
Accelerate the process of getting vaccinated: factors associated with consideration of and accessibility to COVID-19 vaccination in metropolises of China
Authors: Tan Yinliang , Xie Zhilan , Qian Ying , Gu Jie , Bai Yundan , Gu Xiaoqing , Ye Zheng , Feng Jianmin , Huang Jiaoling 
Published: June 2022

Abstract
Background
Rapid mutation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is sweeping the world and delaying the full reopening of society. Acceleration of the vaccination process may be the key element in winning the race against this virus. We examine factors associated with personal considerations of and accessibility to the corona virus disease 2019 (COVID-19) vaccination in metropolises of China.

Methods
This multi-center, cross-sectional research was conducted using online questionnaires from April 1 to June 1, 2021, in community health service centers of Shanghai, Chengdu and Fuzhou. 9,047 vaccinated participants were included and data for 8,990 individuals were eligible for analysis. Chi-square test was conducted to find potential predictors, which were included in the logistic regressions. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the influence of region, socio-economic status (SES), and attitudes on vaccination process.

Results
In consideration phase, participants in Fuzhou (OR:2.26, 95%CI: 1.90 to 2.68) and Chengdu (OR: 2.48, 95%CI: 2.17 to 2.83) were more likely than those in Shanghai to consider longer than one month. These odds increased for participants with master or above degree (reference: illiteracy and primary school), higher monthly household income (reference: < ¥5000), and greater vaccination hesitancy (reference: low hesitancy). Unemployed and household-based participants (OR: 3.37, 95%CI: 1.69 to 6.75, reference: farmer) and participants without brand preference (OR:1.13, 95%CI:1.02 to 1.26) may take longer time of consideration. In the accessibility phase, participants in Fuzhou (OR: 8.82, 95%CI: 7.28 to 10.68) and Chengdu (OR: 2.28, 95%CI: 1.98 to 2.63) were more likely to wait longer than one week. These odds decreased for participants with master or above degree (reference: illiteracy and primary school), monthly household income from ¥5000 to ¥10,000 (reference: < ¥5000), and teacher or student (reference: farmer). Participants without brand preference (OR: 0.86, 95%CI: 0.77 to 0.95) were likely to wait shorter after appointment, while participants with higher risk awareness of domestic epidemic (medium, OR: 1.24, 95%CI: 1.12 to 1.37, reference: low) may wait longer.

Conclusions
The influential factors changed over two phases of vaccination process. Regional disparity affected both consideration and accessibility phases. Expect that, SES, and hesitancy were major factors of the consideration phase, but had limited impact on accessibility phase.
The burden of premature mortality among older adults: a population-based study in Malaysia
Authors: Chan Yee Mang , Ganapathy Shubash Shander , Tan LeeAnn , Alias Nazirah , Nasaruddin Nur Hamizah , Khaw Wan-Fei 
Published: June 2022

Abstract
Background
The populations of many countries—including Malaysia—are rapidly growing older, causing a shift in leading causes of disease and death. In such rapidly ageing populations, it is critical to monitor trends in burden of disease and health of older adults by identifying the leading causes of premature mortality and measuring years of life lost (YLL) to these. The objective of this study, therefore, is to describe the burden (quantified by YLL) associated with major causes of premature mortality among older adults in Malaysia in 2019.

Methods
All deaths that occurred in older adults aged 60 and above in Malaysia in the year 2019 were included in this study. YLL was calculated by summing the number of deaths for the disease category at 5-year age intervals, multiplied by the remaining life expectancy for the specific age and sex group. Both life expectancy and mortality data were obtained from the Department of Statistics Malaysia.

Results
In 2019, older adults accounted for 67.4% of total deaths in Malaysia (117,102 out of 173,746). The total number of YLL among older adults in Malaysia in 2019 was estimated at 1.36 million YLL, accounting for 39.6% of the total YLL (3.44 million) lost to all premature deaths in that year. The major causes of premature mortality among older adults were ischaemic heart disease (29.5%) followed by cerebrovascular disease (stroke) (20.8%), lower respiratory infections (15.9%), diabetes mellitus (8.1%) and trachea, bronchus and lung cancers (5.0%).

Conclusions
Non-communicable diseases (NCD) remained the largest contributor to premature mortality among older adults in Malaysia. Implementation of population-level NCD health promotion programmes, screening programmes among high-risk groups and holistic intervention programmes among populations living with NCD are critical in reducing the overall burden of premature mortality.
Measuring sustainable employability: psychometric properties of the capability set for work questionnaire
Authors: Gürbüz Sait , Joosen Margot C. W. , Kooij Dorien T. A. M. , Bakker Arnold B. , van der Klink Jac J. L. , Brouwers Evelien P. M. 
Published: June 2022

AbstractBackgroundThe capability set for work questionnaire (CSWQ) is being used to measure the new model of sustainable employability building on the capability approach. However, previous studies on the psychometric properties of the instrument are limited and cross-sectional. This two-way study aimed to (1) evaluate the convergent validity of the CSWQ with the theoretically related constructs person-job fit, strengths use, and opportunity to craft and (2) test the predictive and incremental validity of the questionnaire for the well-established work outcomes, including work ability, work engagement, job satisfaction, and task performance.MethodsA representative sample of 303 Dutch workers, chosen with probably random sampling, were surveyed using a one-month follow-up, cross-lagged design via the Longitudinal Internet Studies for the Social Sciences panel. The convergent validity was assessed by exploring the strength of associations between the capability set for work questionnaire and the theoretically related constructs using Pearson’s correlations. The predictive and incremental validity was evaluated by performing a series of linear hierarchical regression analyses.ResultsWe found evidence of the convergent validity of the capability set score by moderate correlations with person-job fit, strengths use, and opportunity to craft (r = 0.51–0.52). A series of multiple regression analyses showed that Time 1 capability set score and its constituents (i.e., importance, ability, and enablement) generally had predictive and incremental validity for work ability, work engagement, job satisfaction, and task performance measured at Time 2. However, the incremental power of the CSWQ over and above conceptually related constructs was modest.ConclusionsThe findings support the convergent, predictive, and incremental validity of the capability set for work questionnaire with not previously investigated work constructs. This provided further evidence to support its utility for assessing a worker’s sustainable employability for future research and practical interventions.
The effect of medication on serum anti-müllerian hormone (AMH) levels in women of reproductive age: a meta-analysis
Authors: Yin Wei-Wei , Huang Chang-Chang , Chen Yi-Ru , Yu Dan-Qing , Jin Min , Feng Chun 
Published: June 2022

Abstract
Objective
The study aims to address whether serum anti-müllerian hormone (AMH) levels fluctuate in the short term after medication application, including oral contraceptives (OCs), metformin (MET), Gonadotropin-releasing hormone agonist (GnRH-a), dehydroepiandrosterone (DHEA), vitamin D (VD), clomiphene citrate (CC), and letrozole (LET).

Methods
Published literature from PubMed, Embase, and Cochrane central was retrieved up until 19 September 2021. A total of 51 self-control studies with an average Newcastle–Ottawa quality assessment scale (NOS) score of 6.90 were analyzed. The extracted data were entered into Stata software, and the weighted mean difference/standardized mean difference (WMD/SMD) and 95% confidence interval (CI) were used for data analysis.

Results
After OCs treatment the AMH level showed a significant decline in women with normal ovarian function, which was significant within 3 months (WMD = -1.43, 95% CI: -2.05 to -0.80, P < 0.00001). After MET treatment, the serum AMH decreased in polycystic ovary syndrome (PCOS) patients (WMD = -1.79, 95% CI: -2.32 to -1.26, P < 0.00001), in both obese and non-obese patients. GnRH-a treatment in endometriosis patients led to dynamic changes in the serum AMH levels, that is, ascent at 1 month (P = 0.05), and descent at 3 months (P = 0.02). After DHEA treatment the serum AMH increased in diminished ovarian reserve (DOR) / poor ovarian response (POR) patients (WMD = 0.18, 95% CI: 0.09 to 0.27, P < 0.0001). After VD treatment the serum AMH increased, and it was obvious in non-PCOS patients (WMD = 0.78, 95% CI: 0.34 to 1.21, P = 0.0004). After CC treatment the serum AMH decreased significantly in PCOS patients, specifically in non-obese patients (WMD = -1.24, 95% CI: -1.87 to -0.61, P = 0.0001).

Conclusions
Serum AMH levels may be affected in the short term after drug application. Specifically, OC, MET and CC lead to decreased AMH level, DHEA and VD lead to increased AMH level, and GnRH-a leads to dynamic variation, which is correlated with PCOS, obesity, age, and duration of medication. The impacts of these medications should be taken into consideration when AMH is used as a marker of ovarian reserve.
Process evaluation of a multi-disciplinary complex intervention to improve care for older patients with chronic conditions in rural areas (the HandinHand Study): study protocol
Authors: Seismann-Petersen Swantje , Köpke Sascha , Inkrot Simone 
Published: June 2022

Abstract
Background
To improve health care in rural areas, especially for increasing numbers of people with chronic diseases, academically qualified nurses could take over expanded roles to meet the challenges of an ageing society and a decreasing number of General Practitioners (GPs). In the project “HandinHand” (HiH), qualified nurses (Expert nurses, ENs) will carry out home visits to older people with chronic diseases over a period of six months. ENs will prepare a care plan in cooperation with GPs to stabilise the care situation and avoid unplanned hospital admissions and GP visits. The process evaluation aims to provide an in-depth analysis of the implementation process and gather important information on barriers and facilitators to the implementation of ENs as a complementary health care structure in primary care, taking into account several context factors.

Methods
Based on the Medical Research Council (MRC) Framework for complex interventions, a logic model was developed and applied as the basis for data collection. Qualitative and quantitative data will be collected during the study. A mixed methods approach should allow to gain important insights from participants (e.g. ENs, GPs, patients) involved in the study as well as relevant stakeholders. Semi-structured interviews and surveys will be conducted. Data analysis will be based on the logical model, combining qualitative and quantitative data. Qualitative data will be analysed inductively-deductively using qualitative thematic framework analysis.

Discussion
The process evaluation will provide guidance and conclusions on further development and transferability. Of particular interest is the expanded role of ENs in primary care, which has barely been implemented in Germany and can be seen as a precursor to the development of an Advanced Practice Nursing (APN) role in primary care.
Vaccine equity in low and middle income countries: a systematic review and meta-analysis
Authors: Ali Huda Ahmed , Hartner Anna-Maria , Echeverria-Londono Susy , Roth Jeremy , Li Xiang , Abbas Kaja , Portnoy Allison , Vynnycky Emilia , Woodruff Kim , Ferguson Neil M , Toor Jaspreet , Gaythorpe Katy AM 
Published: June 2022

Abstract
Background
Evidence to date has shown that inequality in health, and vaccination coverage in particular, can have ramifications to wider society. However, whilst individual studies have sought to characterise these heterogeneities in immunisation coverage at national level, few have taken a broad and quantitative view of the contributing factors to heterogeneity in immunisation coverage and impact, i.e. the number of cases, deaths, and disability-adjusted life years averted. This systematic review aims to highlight these geographic, demographic, and sociodemographic characteristics through a qualitative and quantitative approach, vital to prioritise and optimise vaccination policies.

Methods
A systematic review of two databases (PubMed and Web of Science) was undertaken using search terms and keywords to identify studies examining factors on immunisation inequality and heterogeneity in vaccination coverage. Inclusion criteria were applied independently by two researchers. Studies including data on key characteristics of interest were further analysed through a meta-analysis to produce a pooled estimate of the risk ratio using a random effects model for that characteristic.

Results
One hundred and eight studies were included in this review. We found that inequalities in wealth, education, and geographic access can affect vaccine impact and vaccination dropout. We estimated those living in rural areas were not significantly different in terms of full vaccination status compared to urban areas but noted considerable heterogeneity between countries. We found that females were 3% (95%CI[1%, 5%]) less likely to be fully vaccinated than males. Additionally, we estimated that children whose mothers had no formal education were 27% (95%CI[16%,36%]) less likely to be fully vaccinated than those whose mother had primary level, or above, education. Finally, we found that individuals in the poorest wealth quintile were 27% (95%CI [16%,37%]) less likely to be fully vaccinated than those in the richest.

Conclusions
We found a nuanced picture of inequality in vaccination coverage and access with wealth disparity dominating, and likely driving, other disparities. This review highlights the complex landscape of inequity and further need to design vaccination strategies targeting missed subgroups to improve and recover vaccination coverage following the COVID-19 pandemic.

Trial registration
Prospero, CRD42021261927
The effect of temperature on physical activity: an aggregated timeseries analysis of smartphone users in five major Chinese cities
Authors: Ho Janice Y. , Goggins William B. , Mo Phoenix K. H. , Chan Emily Y. Y. 
Published: June 2022

Abstract
Background
Physical activity is an important factor in premature mortality reduction, non-communicable disease prevention, and well-being protection. Climate change will alter temperatures globally, with impacts already found on mortality and morbidity. While uncomfortable temperature is often perceived as a barrier to physical activity, the actual impact of temperature on physical activity has been less well studied, particularly in China. This study examined the associations between temperature and objectively measured physical activity among adult populations in five major Chinese cities.

Methods
Aggregated anonymized step count data was obtained between December 2017-2018 for five major Chinese cities: Beijing, Shanghai, Chongqing, Shenzhen, and Hong Kong. The associations of temperature with daily aggregated mean step count were assessed using Generalized Additive Models (GAMs), adjusted for meteorological, air pollution, and time-related variables.

Results
Significant decreases in step counts during periods of high temperatures were found for cold or temperate climate cities (Beijing, Shanghai, and Chongqing), with maximum physical activity occurring between 16 and 19.3 °C. High temperatures were associated with decreases of 800-1500 daily steps compared to optimal temperatures. For cities in subtropical climates (Shenzhen and Hong Kong), non-significant declines were found with high temperatures. Overall, females and the elderly demonstrated lower optimal temperatures for physical activity and larger decreases of step count in warmer temperatures.

Conclusions
As minor reductions in physical activity could consequentially affect health, an increased awareness of temperature’s impact on physical activity is necessary. City-wide adaptations and physical activity interventions should seek ways to sustain physical activity levels in the face of shifting temperatures from climate change.
A rare case of highly differentiated follicular carcinoma in ovary with FGFR4 Gly388Arg polymorphism: a case report and literature review
Authors: Bao Yi-Ting , Wang Chao , Huang Wu , Yao Liang-Qing , Yuan Lei 
Published: June 2022

Abstract
Background
Highly differentiated follicular carcinoma (HDFCO) is a rare form of struma-derived thyroid-type carcinoma in ovary, defined as ovarian struma spreading beyond ovary but consisting of benign thyroid tissues. No more than 30 cases of HDFCO have been reported since it was first recognized in 2008. The clinicopathologic and molecular features of HDFCO remain unclear up till now.

Case presentation
A 38-year-old, para 1 gravida 5 woman has a long history of recurrent right ovarian cysts. Histological evaluation showed the tumor progressed from ovarian mature cystic teratoma (OMCT) to highly differentiated follicular carcinoma (HDFCO) during three relapses. Whole-exome sequencing revealed the germline FGFR4 Gly388Arg polymorphism. Repeated operations were performed to remove lesions for the first two relapses. On the third recurrence, the patient received radical surgery with subsequent thyroidectomy and radioactive iodine ablation. No evidence of disease was observed by February 2022 (8 months).

Conclusions
The germline FGFR4 Gly388Arg polymorphism may accelerate the malignant transformation of HDFCO, probably by working as a second hit in the developing spectrum.
Expert clinical pharmacological advice may make an antimicrobial TDM program for emerging candidates more clinically useful in tailoring therapy of critically ill patients
Authors: Gatti Milo , Cojutti Pier Giorgio , Bartoletti Michele , Tonetti Tommaso , Bianchini Amedeo , Ramirez Stefania , Pizzilli Giacinto , Ambretti Simone , Giannella Maddalena , Mancini Rita , Siniscalchi Antonio , Viale Pierluigi , Pea Federico 
Published: June 2022

Abstract
Background
Therapeutic drug monitoring (TDM) may represent an invaluable tool for optimizing antimicrobial therapy in septic patients, but extensive use is burdened by barriers. The aim of this study was to assess the impact of a newly established expert clinical pharmacological advice (ECPA) program in improving the clinical usefulness of an already existing TDM program for emerging candidates in tailoring antimicrobial therapy among critically ill patients.

Methods
This retrospective observational study included an organizational phase (OP) and an assessment phase (AP). During the OP (January–June 2021), specific actions were organized by MD clinical pharmacologists together with bioanalytical experts, clinical engineers, and ICU clinicians. During the AP (July–December 2021), the impact of these actions in optimizing antimicrobial treatment of the critically ill patients was assessed. Four indicators of performance of the TDM-guided real-time ECPA program were identified [total TDM-guided ECPAs July–December 2021/total TDM results July–December 2020; total ECPA dosing adjustments/total delivered ECPAs both at first assessment and overall; and turnaround time (TAT) of ECPAs, defined as optimal (< 12 h), quasi-optimal (12–24 h), acceptable (24–48 h), suboptimal (> 48 h)].

Results
The OP allowed to implement new organizational procedures, to create a dedicated pathway in the intranet system, to offer educational webinars on clinical pharmacology of antimicrobials, and to establish a multidisciplinary team at the morning bedside ICU meeting. In the AP, a total of 640 ECPAs were provided for optimizing 261 courses of antimicrobial therapy in 166 critically ill patients. ECPAs concerned mainly piperacillin–tazobactam (41.8%) and meropenem (24.9%), and also other antimicrobials had ≥ 10 ECPAs (ceftazidime, ciprofloxacin, fluconazole, ganciclovir, levofloxacin, and linezolid). Overall, the pre–post-increase in TDM activity was of 13.3-fold. TDM-guided dosing adjustments were recommended at first assessment in 61.7% of ECPAs (10.7% increases and 51.0% decreases), and overall in 45.0% of ECPAs (10.0% increases and 35.0% decreases). The overall median TAT was optimal (7.7 h) and that of each single agent was always optimal or quasi-optimal.

Conclusions
Multidisciplinary approach and timely expert interpretation of TDM results by MD Clinical Pharmacologists could represent cornerstones in improving the cost-effectiveness of an antimicrobial TDM program for emerging TDM candidates.