bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of the duration of the capecitabine regimen following colon cancer surgery in an elderly population: a retrospective cohort study
Authors: Chen Weiwei , Dong Hongmin , Wang Gang , Chen Juan , Wang Wenling 
Published: August 2021

Abstract
Background
Only 50–70% of elderly colon cancer patients could complete the recommended 6 months of postoperative chemotherapy. It is unknown whether a shorter duration of postoperative capecitabine-alone chemotherapy would compromise survival. We thus conducted this study to analyze the association between postoperative chemotherapy duration of a capecitabine-alone regimen and cancer-specific survival (CSS) and disease-free survival (DFS) of surgery-treated elderly colon cancer patients.

Methods
We performed a retrospective cohort study of surgically treated stage III and high-risk stage II colon cancer patients aged ≥ 70 treated at two medical centers. Cox proportional hazard regression models were utilized to calculate crude and adjusted hazard ratios (HRs). The nonlinear relationship between postoperative chemotherapy duration and survival was analyzed through restricted cubic spline regression analysis, and the threshold effect was calculated by the two-piecewise Cox proportional hazard model.

Results
A total of 1217 surgery-treated colon cancer patients between August 1, 2013, and September 1, 2019, were reviewed, and 257 stage III and high-risk stage II patients aged ≥ 70 were enrolled. Postoperative chemotherapy with capecitabine was administered to 114 patients, and 143 patients only received surgery. As the duration of chemotherapy increased by 1 week, the risk of cancer-specific death was reduced by 11% (HR = 0.89, 95% confidence interval (CI) 0.82–0.96), and the risk of recurrence was reduced by 10% (HR = 0.90, 0.82–0.96). Nonlinearity exploration suggested a threshold effect of capecitabine duration on CSS in stage III disease. The HR for death was 0.79 (95% CI, 0.68–0.92) with duration ≤ 16 weeks and 1.34 (95% CI, 0.91–1.97) with duration > 16 weeks.

Conclusions
The postoperative capecitabine duration was significantly associated with a decrease in death risk and recurrence risk in elderly colon cancer patients. However, the threshold effect of capecitabine duration on survival suggests that short-term chemotherapy may improve survival in elderly stage III colon cancer patients.
Comment on “Pooled analysis of Xpert bladder cancer based on the 5 mRNAs for rapid diagnosis of bladder carcinoma”
Authors: Sharma Gopal 
Published: August 2021

AbstractThis article is a commentary on an article published in World Journal of Surgical Oncology by Liu et al. With this study, authors evaluated diagnostic accuracy of Xpert bladder cancer monitor in detecting recurrences. With this article, we highlight the strengths and limitations of the study.
Tranexamic acid for the prevention and treatment of bleeding in surgery, trauma and bleeding disorders: a narrative review
Authors: Ockerman Anna , Vanassche Thomas , Garip Melisa , Vandenbriele Christophe , Engelen Matthias M , Martens Jeroen , Politis Constantinus , Jacobs Reinhilde , Verhamme Peter 
Published: August 2021

AbstractObjectivesWe review the evidence for tranexamic acid (TXA) for the treatment and prevention of bleeding caused by surgery, trauma and bleeding disorders. We highlight therapeutic areas where evidence is lacking and discuss safety issues, particularly the concern regarding thrombotic complications.MethodsAn electronic search was performed in PubMed and the Cochrane Library to identify clinical trials, safety reports and review articles.FindingsTXA reduces bleeding in patients with menorrhagia, and in patients undergoing caesarian section, myomectomy, hysterectomy, orthopedic surgery, cardiac surgery, orthognathic surgery, rhinoplasty, and prostate surgery. For dental extractions in patients with bleeding disorders or taking antithrombotic drugs, as well as in cases of idiopathic epistaxis, tonsillectomy, liver transplantation and resection, nephrolithotomy, skin cancer surgery, burn wounds and skin grafting, there is moderate evidence that TXA is effective for reducing bleeding. TXA was not effective in reducing bleeding in traumatic brain injury and upper and lower gastrointestinal bleeding. TXA reduces mortality in patients suffering from trauma and postpartum hemorrhage. For many of these indications, there is no consensus about the optimal TXA dose. With certain dosages and with certain indications TXA can cause harm, such as an increased risk of seizures after high TXA doses with brain injury and cardiac surgery, and an increased mortality after delayed administration of TXA for trauma events or postpartum hemorrhage. Whereas most trials did not signal an increased risk for thrombotic events, some trials reported an increased rate of thrombotic complications with the use of TXA for gastro-intestinal bleeding and trauma.ConclusionsTXA has well-documented beneficial effects in many clinical indications. Identifying these indications and the optimal dose and timing to minimize risk of seizures or thromboembolic events is work in progress.
Social media, vaccine hesitancy and trust deficit in immunization programs: a qualitative enquiry in Malappuram District of Kerala, India
Authors: Nair Anoop T. , Nayar Kesavan Rajasekharan , Koya Shaffi Fazaludeen , Abraham Minu , Lordson Jinbert , Grace Chitra , Sreekumar Sreekutty , Chembon Priya , Swarnam Kamala , Pillai A. Marthanda , Pandey Anant Kumar 
Published: August 2021

Abstract
Background
With increased penetration of the internet and social media, there are concerns regarding its negative role in influencing parents’ decisions regarding vaccination for their children. It is perceived that a mix of religious reasons and propaganda by anti-vaccination groups on social media are lowering the vaccination coverage in Malappuram district of Kerala. We undertook a qualitative study to understand the factors responsible for generating and perpetuating vaccine hesitancy, the pathways of trust deficit in immunization programs and the interaction between various social media actors.

Methods
In-depth interviews and focus group discussions were conducted among parents/caregivers, physicians, public sector health staff, alternative system medical practitioners, field healthcare workers and teachers in areas with highest and lowest vaccination coverage in the district, as well as with communication experts.

Results
The trust deficit between parents/caregivers and healthcare providers is created by multiple factors, such as providers’ lack of technical knowledge, existing patriarchal societal norms and critical views of vaccine by naturopaths and homeopaths. Anti-vaccine groups use social media to influence caregivers' perceptions and beliefs. Religion does not appear to play a major role in creating vaccine resistance in this setting.

Conclusions
A long-term, multipronged strategy should be adopted to address the trust deficit. In the short to medium term, the health sector can focus on appropriate and targeted vaccine-related communication strategies, including the use of infographics, soft skills training for healthcare workers, technical competency improvement through a mobile application-based repository of information and creation of a media cell to monitor vaccine-related conversations in social media and to intervene if needed.
Cross-cutting lessons from the Decision-Maker Led Implementation Research initiative
Authors: Mancuso Arielle , Ahmed Malm Shahira , Sharkey Alyssa , Shahabuddin A. S. M. , Shroff Zubin Cyrus 
Published: August 2021

AbstractBackgroundAlmost 20 million children under one year of age did not receive basic vaccines in 2019, and most of these children lived in low- and middle-income countries. Implementation research has been recognized as an emerging area that is critical to strengthen the implementation of interventions proven to be effective. As a component of strengthening implementation, WHO has called for greater embedding of research within decision-making processes. One strategy to facilitate the embedding of research is to engage decision-makers as Principal Investigators of the research. Since 2015, the Alliance for Health Policy and Systems Research within the WHO and the United Nations Children’s Fund have supported decision-maker led research by partnering with Gavi, the Vaccine Alliance, in an initiative called "Decision-Maker Led Implementation Research". This synthesis paper describes the cross-cutting lessons from the initiative to further understand and develop future use of the decision-maker led strategy.MethodsThis study used qualitative methods of data collection, including a document review and in-depth interviews with decision-makers and researchers engaged in the initiative. Document extraction and thematic content analysis were applied. The individual project was the unit of analysis and the results were summarized across projects.ResultsResearch teams from 11 of the 14 projects participated in this study, for an overall response rate of 78.6%. Most projects were carried out in countries in Africa and conducted at the sub-state or sub-district level. Seven enablers and five barriers to the process of conducting the studies or bringing about changes were identified. Key enablers were the relevance, acceptability, and integration of the research, while key barriers included unclear results, limited planning and support, and the limited role of a single study in informing changes to strengthen implementation.ConclusionsDecision-maker led research is a promising strategy to facilitate the embedding of research into decision-making processes and contribute to greater use of research to strengthen implementation of proven-effective interventions, such as immunization. We identified several lessons for consideration in the future design and use of the decision-maker led strategy.
A qualitative study of the development and utilization of health facility-based immunization microplans in Uganda
Authors: Mafigiri David Kaawa , Iradukunda Constance , Atumanya Catherine , Odie Michael , Mancuso Arielle , Tran Nhan , McGrath Janet , Luzze Henry 
Published: August 2021

Abstract
Background
In 2006, Uganda adopted the Reaching Every District strategy with the goal of attaining at least 80% coverage for routine immunizations in every district. The development and utilization of health facility/district immunization microplans is the key to the strategy. A number of reports have shown suboptimal development and use of microplans in Uganda. This study explores factors associated with suboptimal development and use of microplans in two districts in Uganda to pinpoint challenges encountered during the microplanning process.

Methods
A qualitative study was conducted comparing two districts: Kapchorwa, with low immunization coverage, and Luwero with high immunization coverage. Data were collected through multilevel observation of health facilities, planning sessions and planning meetings; records review of microplans, micromaps and meeting minutes; 57 interviews with health workers at the ministry level and lower-level health facility workers. Data were analysed using NVivo 8 qualitative text analysis software. Transcripts were coded, and memos and display matrices were developed to examine the process of developing and utilizing microplans, including experiences of health workers (implementers).

Results
Three key findings emerged from this study. First, there are significant knowledge gaps with regard to the microplanning process among health workers at all levels (community and district health facility and nationally). Limited knowledge about communities and programme catchment areas greatly hinders the planning process by limiting the ability to identify hard-to-reach areas and to prioritize areas according to need. Secondly, the microplanning tool is bulky and complex. Finally, microplanning is being implemented in the context of already overtasked health personnel who have to conduct several other activities as part of their daily routines.

Conclusions
In order to achieve quality improvement as outlined in the Reaching Every District campaign, the microplanning process should be revised. Health workers’ misunderstanding and limited knowledge about the microplanning process, especially at peripheral health facilities, coupled with the complex, bulky nature of the microplanning tool, reduces the effectiveness of microplanning in improving routine immunization in Uganda. This study reveals the need to reduce the complexity of the tool and to identify ways to train and support workers in the use of the revised tool, including support in incorporating the microplanning process into their busy schedules.
Economic burden and health related quality of life of ultra-rare Gaucher disease in China
Authors: Qi Xinye , Xu Jiao , Shan Linghan , Li Ye , Cui Yu , Liu Huan , Wang Kexin , Gao Lijun , Kang Zheng , Wu Qunhong 
Published: August 2021

AbstractBackgroundThe diagnosis and health care of patients with rare diseases present a tremendous challenge worldwide. This study described the health care service utilization through participants’ perspective and estimated the cost of illness (COI), and patients with Gaucher disease (GD)’s/caregivers’ health-related quality of life in China.MethodAn online retrospective survey of patients with GD and their caregivers was conducted during May–June 2018. Socio-demographic, health service utilization, disease-related expenses, social support, sleep quality (Pittsburgh Sleep Quality Index [PSQI]), and the Short Form Health Survey (SF-36) were investigated. Using self-reported information, we estimated the annual COI, including direct healthcare, direct non-healthcare, and indirect costs.ResultsForty patients and their 49 caregivers were surveyed. The patients’ onset age of GD was 9.3 ± 10.9; their disease course was 3.5 ± 3.1 years. 21 (42.9%) patients had ≥ 2 caregivers, but 35 (71.4%) caregivers reported have no experience as a caregiver. 79.6% caregivers have stopped working, and 87.8% changed weekly working schedule. Before final diagnosis, patients visited 3.9 ± 3.1 (max = 20) hospitals and took 1.2 ± 1.7 (max = 6.6) years for confirmed diagnosis. On average, 5.0 ± 9.6 misdiagnoses occurred, and the per-patient diagnoses cost was USD ($) 7576. After GD confirmation, 8 (16.3%) patients received no treatment, 40 (81.6%) received pharmacotherapy, 10 (20.4%) received surgery, 38 (77.6%) received outpatient service (8.8 ± 9.1 times/annually), and 37 (77.5%) received inpatient service (4.0 ± 3.5 times/annually). Annual per-patient COI was USD ($) 49,925 (95% confidence interval: 29,178, 70,672). Average direct healthcare cost was $41,816, including pharmaceutical ($29,908), inpatient ($7,451), and outpatient ($1,838). Productivity loss per-caregiver was $1,980, and their Zarit Burden Inventory score was moderate-severe (48.6 ± 19.6). Both patients/caregivers reported lower social support (32.4 ± 7.4, 34.9 ± 7.6), two times higher PSQI (7.9 ± 2.9, 8.7 ± 3.6), and half lower SF-36 (41.3 ± 18.6, 46.5 ± 19.3) than those reported for healthy Chinese individuals.ConclusionsThe high misdiagnosis rate, together with delayed diagnosis, substantial costs, and deteriorated health-related quality of life of GD patients as well as their heavy care burden, calls for extreme attention from policymakers in China. Further efforts of government and society are urgently demanded, including pharmaceutical reimbursement, screening newborns, developing precise diagnostic tools, and training doctors.
Microglial inclusions and neurofilament light chain release follow neuronal α-synuclein lesions in long-term brain slice cultures
Authors: Barth Melanie , Bacioglu Mehtap , Schwarz Niklas , Novotny Renata , Brandes Janine , Welzer Marc , Mazzitelli Sonia , Häsler Lisa M. , Schweighauser Manuel , Wuttke Thomas V. , Kronenberg-Versteeg Deborah , Fog Karina , Ambjørn Malene , Alik Ania , Melki Ronald , Kahle Philipp J. , Shimshek Derya R. , Koch Henner , Jucker Mathias , Tanriöver Gaye 
Published: August 2021

Abstract
Background
Proteopathic brain lesions are a hallmark of many age-related neurodegenerative diseases including synucleinopathies and develop at least a decade before the onset of clinical symptoms. Thus, understanding of the initiation and propagation of such lesions is key for developing therapeutics to delay or halt disease progression.

Methods
Alpha-synuclein (αS) inclusions were induced in long-term murine and human slice cultures by seeded aggregation. An αS seed-recognizing human antibody was tested for blocking seeding and/or spreading of the αS lesions. Release of neurofilament light chain (NfL) into the culture medium was assessed.

Results
To study initial stages of α-synucleinopathies, we induced αS inclusions in murine hippocampal slice cultures by seeded aggregation. Induction of αS inclusions in neurons was apparent as early as 1week post-seeding, followed by the occurrence of microglial inclusions in vicinity of the neuronal lesions at 2–3 weeks. The amount of αS inclusions was dependent on the type of αS seed and on the culture’s genetic background (wildtype vs A53T-αS genotype). Formation of αS inclusions could be monitored by neurofilament light chain protein release into the culture medium, a fluid biomarker of neurodegeneration commonly used in clinical settings. Local microinjection of αS seeds resulted in spreading of αS inclusions to neuronally connected hippocampal subregions, and seeding and spreading could be inhibited by an αS seed-recognizing human antibody. We then applied parameters of the murine cultures to surgical resection-derived adult human long-term neocortical slice cultures from 22 to 61-year-old donors. Similarly, in these human slice cultures, proof-of-principle induction of αS lesions was achieved at 1week post-seeding in combination with viral A53T-αS expressions.

Conclusion
The successful translation of these brain cultures from mouse to human with the first reported induction of human αS lesions in a true adult human brain environment underlines the potential of this model to study proteopathic lesions in intact mouse and now even aged human brain environments.
Cerebrospinal fluid cell count variability is a major confounding factor in external ventricular drain-associated infection surveillance diagnostics: a prospective observational study
Authors: Bådholm Marcus , Blixt Jonas , Glimåker Martin , Ternhag Anders , Hedlund Jonas , Nelson David W. 
Published: August 2021

AbstractBackgroundExternal ventricular drain (EVD)-related infections (EVDIs) are feared complications that are difficult to rapidly and correctly diagnose, which can lead to unnecessary treatment with broad-spectrum antibiotics. No readily available diagnostic parameters have been identified to reliably predict or identify EVDIs. Moreover, intraventricular hemorrhage is common and affect cerebrospinal fluid (CSF) cellularity. The relationship between leukocytes and erythrocytes is often used to identify suspected infection and triggers the use of antibiotics pending results of cultures, which may take days. Cell count based surveillance diagnostics assumes a homogeneous distribution of cells in the CSF. Given the intraventricular sedimentation of erythrocytes on computed tomography scans this assumption may be erroneous and could affect diagnostics.AimsTo evaluate the consistency of cell counts in serially sampled CSF from EVDs, with and without patient repositioning, to assess the effect on infection diagnostics.MethodsWe performed a prospective single-center study where routine CSF sampling was followed by a second sample after 10 min, allocated around a standard patient repositioning, or not. Changes in absolute and pairwise cell counts and ratios were analyzed, including mixed regression models.ResultsData from 51 patients and 162 paired samples were analyzed. We observed substantial changes in CSF cellularity as the result of both resampling and repositioning, with repositioning found to be an independent predictor of bidirectional cellular change. Glucose and lactate levels were affected, however clinically non-significant. No positive CSF cultures were seen during the study. Thirty percent (30%) of patients changed suspected EVDI status, as defined by the cell component of local and national guidelines, when resampling after repositioning.ConclusionsCSF cell counts are not consistent and are affected by patient movement suggesting a heterogeneity in the intraventricular space. The relationship between leukocytes and erythrocytes was less affected than absolute changes. Importantly, cell changes are found to increase with increased cellularity, often leading to changes in suspected EVDI status. Faster and more precise diagnostics are needed, and methods such as emerging next generation sequencing techniques my provide tools to more timely and accurately guide antibiotic treatment.Trial RegistrationNCT04736407, Clinicaltrials.gov, retrospectively registered 2nd February 2021.
Comparison of iguratimod and conventional cyclophosphamide with sequential azathioprine as treatment of active lupus nephritis: study protocol for a multi-center, randomized, controlled clinical trial (iGeLU study)
Authors: Yan Qingran , Du Fang , Kang Yuening , Ye Ping , Wang Xiaodong , Xu Jianhua , Tang Jianping , Wang Niansong , Jiang Gengru , Li Zhijun , Wang Xuan , Xue Qin , Huang Xinfang , Zhang Xiaoyan , Zhou Ying , Dai Min , Bao Chunde 
Published: August 2021

AbstractBackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease that can involve multiple organs or systems. Lupus nephritis (LN) is associated with high mortality and morbidity. However, plenty of patients do not respond to present treatment or relapse. Iguratimod (IGU) is a new small molecular, anti-rheumatic drug and has shown the potential for drug repurposing from rheumatoid arthritis (RA) to LN treatment. It has been approved for treating RA in northeast Asia. Beyond expectation in a recent observational study, over 90% of thirteen refractory LN patients responded to iguratimod monotherapy in 24 weeks, with no steroids dose increasing or any other medication add-on during the entire follow-up.Methods/designThis study is a multi-center, randomized, 52-week parallel positive drug-controlled study. The study was designed as a head-to-head comparison between the iguratimod and present first-line therapy on LN patients. A total of 120 patients (60 patients each group) is in the enrolling plan. All enrolled patients are assigned randomly into trial and control groups. The patients will be selected from six study sites in China and will all have biopsy-proven active lupus nephritis. In the first 24 weeks of the trial, IGU is compared with cyclophosphamide as an induction therapy, and in the second 24 weeks, IGU is compared with azathioprine as a maintenance therapy. The primary outcome is renal remission rate including both complete remission and partial remission at week 52, which will be analyzed using a non-inferiority hypothesis test.DiscussionMost patients diagnosed with SLE will develop LN within 5 years and LN remains a major cause of morbidity and death for SLE patients. Although some medications are proven effective for the treatment of this condition, at least 20–35% LN patients have to suffer from relapse or ineffective treatment and medication intolerance is also frequent. This trial is designed to demonstrate whether iguratimod can be used as an alternative induction or maintenance therapy in subjects who have lupus nephritis. Data from this study will provide an evidence on whether or not iguratimod should be recommended to active LN patients.Trial registrationClinicalTrials.govNCT 02936375. Registered on October 18, 2016.