bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of adverse effects of chemotherapy regimens of 5-fluoropyrimidines derivatives and their association with DPYD polymorphisms in colorectal cancer patients
Authors: Negarandeh Reza , Salehifar Ebrahim , Saghafi Fatemeh , Jalali Hossein , Janbabaei Ghasem , Abdhaghighi Mohammad Javad , Nosrati Anahita
Published: June 2020

Background

5-Fluorouracil (5-FU) and capecitabine are fluoropyrimidine derivatives that mainly metabolized with dihydropyrimidine dehydrogenase enzyme (DPD). The genetic polymorphism in the genes encoding this enzyme may result in a decrease or loss of enzyme activity which may lead to the accumulation of medicines, their metabolites and potential toxicity.

Method

This cross-sectional study was conducted on 88 participants with colorectal cancer (CRC). After DNA extraction, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the DPD gene (DPYD) polymorphisms including IVS 14 + 1 G > A, 2846 A > T and 2194 G > A. Chemotherapy-induced side effects were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0).

Result

Data were collected from 227 chemotherapy cycles of 88 patients with CRC. In a comparison of FOLFOX and FOLFIRI regimens, there was no significant difference in the occurrence of chemotherapy-induced diarrhea, nausea, vomiting and oral mucositis. However, the peripheral neuropathy was more frequent in patients who were treated with FOLFOX (P <  0.001) and hair loss was more common in patients who received FOLFIRI regimen (P = 0.048).

Incidence of the DPD IVS14 + 1 G > A polymorphism was observed in four patients (5.5%). There was no association between IVS14 + 1 G > A polymorphism and the occurrence of adverse reactions.

Conclusion

FOLFOX and FOLFIRI were the most common regimens in CRC patients and their toxicity profile was different in some adverse reactions. Prevalence of IVS14 + 1G > A variant was relatively higher than other similar studies.

Trial registration

Approval code; IR.MAZUMS.REC.95.2480.
Black patients referred to a lung cancer screening program experience lower rates of screening and longer time to follow-up
Authors: Lake Michael , Shusted Christine S. , Juon Hee-Soon , McIntire Russell K. , Zeigler-Johnson Charnita , Evans Nathaniel R. , Kane Gregory C. , Barta Julie A.
Published: June 2020

Background

Racial disparities are well-documented in preventive cancer care, but they have not been fully explored in the context of lung cancer screening. We sought to explore racial differences in lung cancer screening outcomes within a lung cancer screening program (LCSP) at our urban academic medical center including differences in baseline low-dose computed tomography (LDCT) results, time to follow-up, adherence, as well as return to annual screening after additional imaging, loss to follow-up, and cancer diagnoses in patients with positive baseline scans.

Methods

A historical cohort study of patients referred to our LCSP was conducted to extract demographic and clinical characteristics, smoking history, and lung cancer screening outcomes.

Results

After referral to the LCSP, blacks had significantly lower odds of receiving LDCT compared to whites, even while controlling for individual lung cancer risk factors and neighborhood-level factors. Blacks also demonstrated a trend toward delayed follow-up, decreased adherence, and loss to follow-up across all Lung-RADS categories.

Conclusions

Overall, lung cancer screening annual adherence rates were low, regardless of race, highlighting the need for increased patient education and outreach. Furthermore, the disparities in race we identified encourage further research with the purpose of creating culturally competent and inclusive LCSPs.
A prognostic model based on cell-cycle control predicts outcome of breast cancer patients
Authors: Repo Heli , Löyttyniemi Eliisa , Kurki Samu , Kallio Lila , Kuopio Teijo , Talvinen Kati , Kronqvist Pauliina
Published: June 2020

Background

A prognostic model combining biomarkers of metaphase-anaphase transition of the cell cycle was developed for invasive breast cancer. The prognostic value and clinical applicability of the model was evaluated in comparison with the routine prognosticators of invasive breast carcinoma.

Methods

The study comprised 1135 breast cancer patients with complete clinical data and up to 22-year follow-up. Regulators of metaphase-anaphase transition were detected immunohistochemically and the biomarkers with the strongest prognostic impacts were combined into a prognostic model. The prognostic value of the model was tested and evaluated in separate patient materials originating from two Finnish breast cancer centers.

Results

The designed model comprising immunoexpressions of Securin, Separase and Cdk1 identified 8.4-fold increased risk of breast cancer mortality (p < 0.0001). A survival difference exceeding 15 years was observed between the majority (> 75%) of patients resulting with favorable as opposed to unfavorable outcome of the model. Along with nodal status, the model showed independent prognostic impact for all breast carcinomas and for subgroups of luminal, N+ and N- disease.

Conclusions

The impact of the proposed prognostic model in predicting breast cancer survival was comparable to nodal status. However, the model provided additional information in N- breast carcinoma in identifying patients with aggressive course of disease, potentially in need of adjuvant treatments. Concerning N+, in turn, the model could provide evidence for withholding chemotherapy from patients with favorable outcome.
Role of DNA methylation in the association of lung function with body mass index: a two-step epigenetic Mendelian randomisation study
Authors: Amaral André F. S. , Imboden Medea , Wielscher Matthias , Rezwan Faisal I. , Minelli Cosetta , Garcia-Aymerich Judith , Peralta Gabriela P. , Auvinen Juha , Jeong Ayoung , Schaffner Emmanuel , Beckmeyer-Borowko Anna , Holloway John W. , Jarvelin Marjo-Riitta , Probst-Hensch Nicole M. , Jarvis Deborah L. ,   for the ALEC consortium
Published: June 2020

Background

Low lung function has been associated with increased body mass index (BMI). The aim of this study was to investigate whether the effect of BMI on lung function is mediated by DNA methylation.

Methods

We used individual data from 285,495 participants in four population-based cohorts: the European Community Respiratory Health Survey, the Northern Finland Birth Cohort 1966, the Swiss Study on Air Pollution and Lung Disease in Adults, and the UK Biobank. We carried out Mendelian randomisation (MR) analyses in two steps using a two-sample approach with SNPs as instrumental variables (IVs) in each step. In step 1 MR, we estimated the causal effect of BMI on peripheral blood DNA methylation (measured at genome-wide level) using 95 BMI-associated SNPs as IVs. In step 2 MR, we estimated the causal effect of DNA methylation on FEV1, FVC, and FEV1/FVC using two SNPs acting as methQTLs occurring close (in cis) to CpGs identified in the first step. These analyses were conducted after exclusion of weak IVs (F statistic < 10) and MR estimates were derived using the Wald ratio, with standard error from the delta method. Individuals whose data were used in step 1 were not included in step 2.

Results

In step 1, we found that BMI might have a small causal effect on DNA methylation levels (less than 1% change in methylation per 1 kg/m2 increase in BMI) at two CpGs (cg09046979 and cg12580248). In step 2, we found no evidence of a causal effect of DNA methylation at cg09046979 on lung function. We could not estimate the causal effect of DNA methylation at cg12580248 on lung function as we could not find publicly available data on the association of this CpG with SNPs.

Conclusions

To our knowledge, this is the first paper to report the use of a two-step MR approach to assess the role of DNA methylation in mediating the effect of a non-genetic factor on lung function. Our findings do not support a mediating effect of DNA methylation in the association of lung function with BMI.
Long-term impact of sagittal malalignment on hardware after posterior fixation of the thoracolumbar spine: a retrospective study
Authors: Elshamly Mahmoud , Windhager Reinhard , Toegel Stefan , Grohs Josef Georg
Published: June 2020

Background

The importance of sagittal alignment in healthy individuals and in reconstructive spinal surgery has been studied over the last 15 years. The aim of the present study was to assess the long-term effects of abnormal sagittal alignment on hardware after posterior thoracolumbar spinal fusion.

Methods

Patients who had undergone revision surgery (revision cohort, n = 34) due to breakage of their implants were compared retrospectively with patients who had intact implants at the final follow-up investigation after a long posterior thoracolumbar and/or lumbar spinal fusion (control cohort, n = 22). Clinical data and radiological parameters including the sagittal vertical axis (SVA), pelvic incidence (PI), lordosis gap (LG), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis (TK), and the femoral obliquity angle (FOA) were assessed on full-spine lateral radiographs obtained in regular standing position. Data were analysed using descriptive statistics, parametric and non-parametric inferential statistics.

Results

Patients in the breakage group (female n = 21, male n = 9, mean age 60.9 ± 15.6 years) had a higher anterior shift of the C7 plumb line (SVA) (p = 0.02), retroversion of the pelvis (PT) (p < 0.001), PI-LL mismatch (LG) (p = 0.001), and PI (p = 0.002) than the intact group (female n = 10, male n = 12, mean age 65.7 ± 12.4 years). No significant difference was registered between groups in regard of SS, LL, TK, FOA, and the mean number of comorbidities.

Conclusion

Failure of restoration of the SVA and the LG to the acceptable ranges, especially in patients with a high PI, may be regarded as a risk factor for the long-term failure of implants after posterior thoracolumbar spinal fusion.
How group coaching contributes to organisational understanding among newly graduated doctors
Authors: Malling Bente , de Lasson Lydia , Just Eva , Stegeager Nikolaj
Published: June 2020

Background

Practising medicine at an expert level requires skills beyond medical expert knowledge. Research shows that newly appointed consultants feel less prepared to deal with leadership issues compared to issues regarding medical expertice. Newly graduated (NG) doctors and residents in particular struggle with leadership and organisational issues.

The purpose of this study was to explore the impact of group coaching on NG doctors’ approach to organisational and leadership challenges in daily practice during the transition period from medical school to clinical work.

Methods

Newly graduated doctors participated in a group coaching course comprising three full-day sessions and five two-hour sessions. The purpose was to support NG doctors’ professional development regarding organisational issues in the first years after graduation. The coaches were health professionals with certified coaching training. Data from the intervention were collected from open-ended questionnaires and observational notes. A thematic analysis was performed.

Results

Forty-five NG doctors participated in a total of six courses sharing experiences and problems reflected in their professional lives. The following themes emerged: Revelation of the hidden curriculum, importance of professional relations, inter-professional communication, conflict management and emerging leadership skills. Participants’ communication skills improved due to an increased awareness of other peoples’ perspectives and preferences. They realized the importance of good relations, saw how they could become active contributors in their departments and began to practice leadership skills through e.g. involvement of the team, delegation of work and negotiation of own obligations.

Conclusion

Newly graduated doctors seemed to develop a growing awareness of organisational issues and a deeper understanding of the complexity of health care organisations through participation in a group coaching course. The study indicates that participation in a group coaching course probably contributes to improve practice among NG doctors. Further studies are needed to consolidate the findings and explore possible organisational effects.
Stratifying patients using fast multiple kernel learning framework: case studies of Alzheimer’s disease and cancers
Authors: Giang Thanh-Trung , Nguyen Thanh-Phuong , Tran Dang-Hung
Published: June 2020

Background

Predictive patient stratification is greatly emerging, because it allows us to prospectively identify which patients will benefit from what interventions before their condition worsens. In the biomedical research, a number of stratification methods have been successfully applied and have assisted treatment process. Because of heterogeneity and complexity of medical data, it is very challenging to integrate them and make use of them in practical clinic. There are two major challenges of data integration. Firstly, since the biomedical data has a high number of dimensions, combining multiple data leads to the hard problem of vast dimensional space handling. The computation is enormously complex and time-consuming. Secondly, the disparity of different data types causes another critical problem in machine learning for biomedical data. It has a great need to develop an efficient machine learning framework to handle the challenges.

Methods

In this paper, we propose a fast-multiple kernel learning framework, referred to as fMKL-DR, that optimise equations to calculate matrix chain multiplication and reduce dimensions in data space. We applied our framework to two case studies, Alzheimer’s disease (AD) patient stratification and cancer patient stratification. We performed several comparative evaluations on various biomedical datasets.

Results

In the case study of AD patients, we enhanced significantly the multiple-ROIs approach based on MRI image data. The method could successfully classify not only AD patients and non-AD patients but also different phases of AD patients with AUC close to 1. In the case study of cancer patients, the framework was applied to six types of cancers, i.e., glioblastoma multiforme cancer, ovarian cancer, lung cancer, breast cancer, kidney cancer, and liver cancer. We efficiently integrated gene expression, miRNA expression, and DNA methylation. The results showed that the classification model basing on integrated datasets was much more accurate than classification model basing on the single data type.

Conclusions

The results demonstrated that the fMKL-DR remarkably improves computational cost and accuracy for both AD patient and cancer patient stratification. We optimised the data integration, dimension reduction, and kernel fusion. Our framework has great potential for mining large-scale cohort data and aiding personalised prevention.
Out of pocket expenditures of patients with a chronic condition consulting a primary care provider in Tajikistan: a cross-sectional household survey
Authors: Fischer Fabienne B. , Mengliboeva Zulfira , Karimova Gulzira , Abdujabarov Nasrullo , Prytherch Helen , Wyss Kaspar
Published: June 2020

Background

Within its reform efforts, the Government of Tajikistan is embracing the essential role of primary health care (PHC) in decreasing out of pocket (OOP) expenditures and increasing equity in access to health services. In the light of the increasing burden of disease relating to chronic conditions, we investigated OOP expenditures of patients with chronic conditions within a PHC setting; and if and how those expenditures are impacted by several interventions currently being implemented within Tajikistan.

Methods

A cross-sectional survey among 1600 adult patients who had visited a PHC facility was conducted. The data obtained through interviews were descriptively analysed, and logistic regressions and gamma generalized linear models were performed.

Results

The total OOP expenditures related to a patient’s last visit to the PHC facility were 17.2 USD for those with chronic conditions and 13.9 USD for those visiting due to an acute condition. Adjustment for potential confounders reduced the discrepancy from 3.3 USD to 0.5 USD. This convergence of costs was only observed in districts covered by the Basic Benefit Package (BBP), a governmental pilot project, aiming to standardise exemptions for payment and formal co-payments for health care services. Hence, we found the BBP to have a protective impact for patients with chronic conditions. However, considering the demographics of these patients (older in age, with greater dependency on pensions and social aid, and lower socio-economic status) in combination with the 40% higher utilisation rate of PHC and the high rate of onward referrals to specialists; it is clear that patients with chronic conditions continue to face substantial long-term costs and disadvantages.

Conclusions

After accounting for confounders, patients with chronic and acute conditions faced similar costs related to a single visit to a PHC facility in districts covered by the BBP. However, greater efforts are required to ensure that citizens are well informed about their rights to health care, the BBP and the services that should be provided at no cost at the point of delivery. Moreover, the needs of patients with chronic conditions warrant a more integrative approach that takes long-term expenditures and services beyond the level of PHC into account.
Interaction between obstructive sleep apnea and short sleep duration on insulin resistance: a large-scale study
Authors: Xu Huajun , Liang Chen , Zou Jianyin , Yi Hongliang , Guan Jian , Gu Meizhen , Feng Yanhong , Yin Shankai
Published: June 2020

Objectives

Both short sleep duration and obstructive sleep apnea (OSA) seem to be associated with insulin resistance. We aimed to explore whether short sleep duration modifies the relationship between OSA and insulin resistance.

Methods

Participants were consecutively enrolled from our sleep center during the period from 2007 to 2017. The index of homeostasis model assessment insulin resistance (HOMA-IR) was calculated from insulin and glucose. Sleep duration was determined by standard polysomnography. The associations between sleep duration and insulin resistance were estimated by logistic regression analyses.

Results

A total of 5447 participants (4507 OSA and 940 primary snorers) were included in the study. OSA was independently correlated with insulin resistance after adjusting for all potential confounders (OR, 1.319; 95% CI, 1.088–1.599), but not short sleep duration. In stratified analysis by sleep duration, compared with primary snorers, in the OSA group only extremely short sleep duration (< 5 h) was significantly associated with insulin resistance after adjusting for all covariates (OR, 2.229; 95% CI, 1.283–3.874). Rapid eye movement predominant OSA was significantly associated with insulin resistance (OR = 1.355, 95% CI: 1.019–1.802) after adjustment for confounding factors including age, sex and body mass index.

Conclusions

OSA, but not short sleep duration, was independently associated with insulin resistance. It is worth noting that OSA combined with extremely short sleep duration showed a greater detrimental effect than OSA itself with regard to insulin resistance.
Circular RNA circ_0000284 plays an oncogenic role in the progression of non-small cell lung cancer through the miR-377-3p-mediated PD-L1 promotion
Authors: Li Li , Zhang Qiaohua , Lian Ke
Published: June 2020

Background

Circular RNAs (circRNAs), a subgroup of non-coding RNAs, are recognized as pivotal mediators in various types of cancers. CircRNA_0000284 (circ_0000284) was manifested to participate in the development of non-small cell lung cancer (NSCLC). The novel functional mechanism of circ_0000284 in NSCLC was investigated in our current study.

Methods

We exploited quantitative real-time polymerase chain reaction (qRT-PCR) to analyze the relative RNA (circRNA, miRNA and mRNA) expression. The assessment of cell proliferation and colony formation was executed by Cell Counting Kit-8 (CCK-8) and colony formation assay, respectively. Transwell assay was implemented to examine cell migration and invasion. All protein levels were assayed using western blot. The role of circ_0000284 in vivo was evaluated via xenograft model. The target relation was estimated by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.

Results

As for the biological characterization, circ_0000284 was highly stable and localized in the cytoplasm. Circ_0000284 was up-regulated in NSCLC and could predict poor prognosis of NSCLC patients. Both in vitro and in vivo, down-regulation of circ_0000284 refrained tumorigenesis of NSCLC. Besides, microRNA-377-3p (miR-377-3p) was a miRNA target of circ_0000284, and targeted programmed death-ligand 1 (PD-L1). Circ_0000284 was a cancer-promoting circRNA in NSCLC via regulating the miR-377-3p/PD-L1 axis.

Conclusion

Thus, our results unraveled that circ_0000284 facilitated the progression of NSCLC by up-regulating the PD-L1 expression as a competing endogenous RNA (ceRNA) of miR-377, possibly developing a different perspective in understanding the molecular pathogenesis of NSCLC.
CircHIPK3 promotes proliferation and metastasis and inhibits apoptosis of renal cancer cells by inhibiting MiR-485-3p
Authors: Lai Jinjin , Xin Jun , Fu Changde , Zhang Wei
Published: June 2020

Background

The intervention of circHIPK3 in renal carcinoma (RC) has not been reported, and thus, the current study investigated the intervention and mechanism of circHIPK3 in RC.

Methods

The expression of circHIPK3 in RC tissues and cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Ribonuclease R (RNase R) resistance and distribution of circHIPK3 and HIPK3 were analyzed by RNase R digestion experiments and cytoplasm/nucleus separation experiments. CircHIPK3 was knocked down in ACHN and 769-P cells. Cell counting kit-8 (CCK-8), colony formation assay, scratch assay, and Transwell assay were performed to detect cell proliferation and metastasis. CircInteractome, qRT-PCR and dual-luciferase reporter assay were used to predict the target miRNAs of circHIPK3. Furthermore, a series of rescue experiments were performed to analyze the regulatory relationship between circHIPK3 and miR-485-3p. Epithelial-mesenchymal transition (EMT) and the expressions of apoptosis-associated markers were detected by Western blot and qRT-PCR. The regulatory relationship between circHIPK3 and miR-485-3p in vivo was explored by xenograft experiments, Western blot, qRT-PCR and immunohistochemistry (Ki-67).

Results

CircHIPK3 was mainly overexpressed in the cytoplasm of RC tissues and cells. Knocking down circHIPK3 inhibited the proliferation, migration, and invasion of RC cells. The expression of circHIPK3 was negatively related to that of its target gene miR-485-3p. Results of the rescue experiments showed that circHIPK3 overexpression could partially reverse the anti-carcinoma effect of miR-485-3p mimic. The specific mechanism of circHIPK3 was related to the effect of miR-485-3p on partially reversing the up-regulated expressions of Clever caspase-3, Bax, E-Cadherin and down-regulated expressions of Bcl-2, N-Cadherin and Vimentin. The results of in vivo experiments demonstrated that circHIPK3 promoted tumor growth and the expression of Ki-67 by down-regulating miR-485-3p.

Conclusion

CircHIPK3 promotes the proliferation and metastasis and inhibits the apoptosis of RC cells through competitively binding to miR-485-3p.
Development of a consensus statement on the role of the family in the physical activity, sedentary, and sleep behaviours of children and youth
Authors: Rhodes Ryan E. , Guerrero Michelle D. , Vanderloo Leigh M. , Barbeau Kheana , Birken Catherine S. , Chaput Jean-Philippe , Faulkner Guy , Janssen Ian , Madigan Sheri , Mâsse Louise C. , McHugh Tara-Leigh , Perdew Megan , Stone Kelly , Shelley Jacob , Spinks Nora , Tamminen Katherine A. , Tomasone Jennifer R. , Ward Helen , Welsh Frank , Tremblay Mark S.
Published: June 2020

Background

Children and youth who meet the physical activity, sedentary, and sleep behaviour recommendations in the Canadian 24-Hour Movement Guidelines are more likely to have desirable physical and psychosocial health outcomes. Yet, few children and youth actually meet the recommendations. The family is a key source of influence that can affect lifestyle behaviours. The purpose of this paper is to describe the process used to develop theConsensus Statement on the Role of the Family in the Physical Activity, Sedentary, and Sleep Behaviours of Children and Youth(0–17 years) and present, explain, substantiate, and discuss the finalConsensus Statement.

Methods

The development of theConsensus Statementincluded the establishment of a multidisciplinary Expert Panel, completion of six reviews (three literature, two scoping, one systematic review of reviews), custom data analyses of Statistics Canada’s Canadian Health Measures Survey, integration of related research identified by Expert Panel members, a stakeholder consultation, establishment of consensus, and the development of a media, public relations, communications and launch plan.

Results

Evidence from the literature reviews provided substantial support for the importance of family on children’s movement behaviours and highlighted the importance of inclusion of the entire family system as a source of influence and promotion of healthy child and youth movement behaviours. The Expert Panel incorporated the collective evidence from all reviews, the custom analyses, other related research identified, and stakeholder survey feedback, to develop a conceptual model and arrive at theConsensus Statement: Families can support children and youth in achieving healthy physical activity, sedentary and sleep behaviours by encouraging, facilitating, modelling, setting expectations and engaging in healthy movement behaviours with them. Other sources of influence are important (e.g., child care, school, health care, community, governments) and can support families in this pursuit.

Conclusion

Family is important for the support and promotion of healthy movement behaviours of children and youth. ThisConsensus Statementserves as a comprehensive, credible, and current synopsis of related evidence, recommendations, and resources for multiple stakeholders.
The influence of timing of surgery in the outcome of spinal cord injury without radiographic abnormality (SCIWORA)
Authors: Qi Can , Xia Hehuan , Miao Dechao , Wang Xingui , Li Zengyan
Published: June 2020

Background

Spinal cord injury without radiographic abnormality (SCIWORA) is a rare traumatic myelopathy. Although surgery is one of the most important treatments, the surgery for SCIWORA is controversial, especially the time of surgery is a topic of controversy. Here, we investigate the effects of difference in duration from injury to surgery on the outcome of SCIWORA.

Methods

This retrospective study was performed in all patients with spinal cord injury admitted to the Third Affiliated Hospital of Hebei Medical University from January 2013 to April 2017. Fifty-seven patients who met the study requirements were divided into 3 groups according to the duration from injury to surgery. Group A (surgery within 3 days of injury) had 18 patients, group B (surgery within 3–7 days) had 18 patients, and group C (surgery later than 7 days) had 21 patients. All the groups were compared with Mann–Whitney U test; the functional improvement of spinal cord was compared and analyzed using the ASIA sports score and ASIA Impairment Scale (AIS).

Results

There was a significant improvement in the long-term AIS (final follow-up) in all the 3 groups compared to before surgery. The final follow-up recovery rate of group C was worse than group A and group B. The curative effect of operation within 7 days was significantly better than the surgery done 7 days later. The recovery rate of group C was worse than group A and B. The ASIA sports score showed that recovery was quicker in the early stage and slow in the later stage.

Conclusions

The optimal schedule of surgical treatment was 3–7 days after injury, which can significantly improve the short-term and long-term follow-up effects. Longer the time to surgery from the time of injury, the worse was the prognosis.
Surgical treatment strategies for extra-pelvic intravenous leiomyomatosis
Authors: Li Hua , Xu Jing , Lin Qiaowei , Zhang Yong , Zhao Yun , Tong Hanxing , Tu Ruiqin , Xu Demin , Wang Chunsheng , Lu Weiqi
Published: June 2020

Background

Extra-pelvic intravenous leiomyomatosis (IVL) extending into inferior vena cava (IVC) or heart (i.e. intracardiac leiomyomatosis, ICL) is an extremely rare benign disease. No consensus has been reached on the optimal surgical strategy. The aim of this study is to introduce four types of one-stage surgical strategies including less invasive options and a guideline to select patient-specific strategy for this disease.

Methods

Twenty-four patients of extra-pelvic IVLs receiving one-stage resections at the Zhongshan Hospital from July 2011 to November 2019 were reviewed retrospectively. Base on the initial experiences of the indiscriminate choices of tumor thrombectomies through sterno-laparotomy under cardiopulmonary bypass (CPB) in 6 ICLs, an anatomy-based guideline for four types of surgical strategies was developed and applied for the next 18 patients.

Results

Under the direction of guideline, tumor thrombectomies through single laparotomy were applied without CPB in 2 ICLs and 4 IVLs confined in IVC, or with CPB in 7 ICLs. Guideline-directed double-incisions with CPB were applied in only 5 ICLs, including 1 receiving mini-thoracotomy and 4 receiving sternotomy because of tumor adherences with right atriums in 2 and with pulmonary arteries in 2. All 24 patients accomplished one-stage panhysterectomy, bilateral adnexectomy and complete resections of intracaval and intracardiac tumors. For residual pelvic intravenous tumors in 19 patients, 17 received macroscopically complete resections while the other 2 failed because of high risk of hemorrhage. Intraoperative blood losses, operation time and hospitalization expense in the single-laparotomy non-CPB group were significantly lesser than the other groups. In CPB groups, inpatient stay and hospitalization expense in the single-incision group were significantly lesser than the double-incisions group. All patients were alive and free of recurrences during a mean follow-up of 35.4 ± 27.2 months (range, 1–100 months). The pelvic tumor residues in 2 patients remained unchanged for 51 and 52 months since operation, respectively.

Conclusions

For various extra-pelvic IVLs, the 4 types of surgical strategies including less invasive options are feasible, providing these are selected by a guideline base on the tumor extension and morphology. The proposed guideline is believed to accommodate more patients receiving less invasive surgery without compromising the curative effect.
The vascular endothelium: the cornerstone of organ dysfunction in severe SARS-CoV-2 infection
Authors: Pons Stéphanie , Fodil Sofiane , Azoulay Elie , Zafrani Lara
Published: June 2020

In severe SARS-CoV-2 infections, emerging data including recent histopathological studies have emphasized the crucial role of endothelial cells (ECs) in vascular dysfunction, immunothrombosis, and inflammation.

Histopathological studies have evidenced direct viral infection of ECs, endotheliitis with diffuse endothelial inflammation, and micro- and macrovascular thrombosis both in the venous and arterial circulations. Venous thrombotic events, particularly pulmonary embolism, with elevated D-dimer and coagulation activation are highly prevalent in COVID-19 patients. The pro-inflammatory cytokine storm, with elevated levels of interleukin-6 (IL-6), IL-2 receptor, and tumor necrosis factor-α, could also participate in endothelial dysfunction and leukocyte recruitment in the microvasculature. COVID-19-induced endotheliitis may explain the systemic impaired microcirculatory function in different organs in COVID-19 patients. Ongoing trials directly and indirectly target COVID-19-related endothelial dysfunctions: i.e., a virus-cell entry using recombinant angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS-2) blockade, coagulation activation, and immunomodulatory therapies, such as anti-IL-6 strategies. Studies focusing on endothelial dysfunction in COVID-19 patients are warranted as to decipher their precise role in severe SARS-CoV-2 infection and organ dysfunction and to identify targets for further interventions.
Hypertonic sodium lactate improves microcirculation, cardiac function, and inflammation in a rat model of sepsis
Authors: Besnier Emmanuel , Coquerel David , Kouadri Geoffrey , Clavier Thomas , Favory Raphael , Duburcq Thibault , Lesur Olivier , Bekri Soumeya , Richard Vincent , Mulder Paul , Tamion Fabienne
Published: June 2020

Background

Hypertonic sodium lactate (HSL) may be of interest during inflammation. We aimed to evaluate its effects during experimental sepsis in rats (cecal ligation and puncture (CLP)).

Methods

Three groups were analyzed (n = 10/group): sham, CLP-NaCl 0.9%, and CLP-HSL (2.5 mL/kg/h of fluids for 18 h after CLP). Mesenteric microcirculation, echocardiography, cytokines, and biochemical parameters were evaluated. Two additional experiments were performed for capillary leakage (Evans blue, n = 5/group) and cardiac hemodynamics (n = 7/group).

Results

HSL improved mesenteric microcirculation (CLP-HSL 736 [407–879] vs. CLP-NaCl 241 [209–391] UI/pixel, p = 0.0006), cardiac output (0.34 [0.28–0.43] vs. 0.14 [0.10–0.18] mL/min/g, p < 0.0001), and left ventricular fractional shortening (55 [46–73] vs. 39 [33–52] %, p = 0.009). HSL also raised dP/dtmax slope (6.3 [3.3–12.1] vs. 2.7 [2.0–3.9] 103 mmHg/s, p = 0.04), lowered left ventricular end-diastolic pressure-volume relation (1.9 [1.1–2.3] vs. 3.0 [2.2–3.7] RVU/mmHg, p = 0.005), and reduced Evans blue diffusion in the gut (37 [31–43] vs. 113 [63–142], p = 0.03), the lung (108 [82–174] vs. 273 [222–445], p = 0.006), and the liver (24 [14–37] vs. 70 [50–89] ng EB/mg, p = 0.04). Lactate and 3-hydroxybutyrate were higher in CLP-HSL (6.03 [3.08–10.30] vs. 3.19 [2.42–5.11] mmol/L, p = 0.04; 400 [174–626] vs. 189 [130–301] μmol/L, p = 0.03). Plasma cytokines were reduced in HSL (IL-1β, 172 [119–446] vs. 928 [245–1470] pg/mL, p = 0.004; TNFα, 17.9 [12.5–50.3] vs. 53.9 [30.8–85.6] pg/mL, p = 0.005; IL-10, 352 [267–912] vs. 905 [723–1243] pg/mL) as well as plasma VEGF-A (198 [185–250] vs. 261 [250–269] pg/mL, p = 0.009).

Conclusions

Hypertonic sodium lactate fluid protects against cardiac dysfunction, mesenteric microcirculation alteration, and capillary leakage during sepsis and simultaneously reduces inflammation and enhances ketone bodies.
Intra-cluster correlation coefficients in primary care patients with type 2 diabetes and hypertension
Authors: Lee Yi Lin , Lim Yvonne Mei Fong , Law Kian Boon , Sivasampu Sheamini
Published: June 2020

Introduction

There are few sources of published data on intra-cluster correlation coefficients (ICCs) amongst patients with type 2 diabetes (T2D) and/or hypertension in primary care, particularly in low- and middle-income countries. ICC values are necessary for determining the sample sizes of cluster randomized trials. Hence, we aim to report the ICC values for a range of measures from a cluster-based interventional study conducted in Malaysia.

Method

Baseline data from a large study entitled Evaluation of Enhanced Primary Health Care interventions in public health clinics (EnPHC-EVA: Facility) were used in this analysis. Data from 40 public primary care clinics were collected through retrospective chart reviews and a patient exit survey. We calculated the ICCs for processes of care, clinical outcomes and patient experiences in patients with T2D and/or hypertension using the analysis of variance approach.

Results

Patient experience had the highest ICC values compared to processes of care and clinical outcomes. The ICC values ranged from 0.01 to 0.48 for processes of care. Generally, the ICC values for processes of care for patients with hypertension only are higher than those for T2D patients, with or without hypertension. However, both groups of patients have similar ICCs for antihypertensive medications use. In addition, similar ICC values were observed for clinical outcomes, ranging from 0.01 to 0.09. For patient experience, the ICCs were between 0.03 (proportion of patients who are willing to recommend the clinic to their friends and family) and 0.25 (for Patient Assessment of Chronic Illness Care item 9, Given a copy of my treatment plan).

Conclusion

The reported ICCs and their respective 95% confidence intervals for T2D and hypertension will be useful for estimating sample sizes and improving efficiency of cluster trials conducted in the primary care setting, particularly for low- and middle-income countries.
Two-by-two factorial randomised study within a trial (SWAT) to evaluate strategies for follow-up in a randomised prevention trial
Authors: Bradshaw Lucy E. , Montgomery Alan A. , Williams Hywel C. , Chalmers Joanne R. , Haines Rachel H.
Published: June 2020

Background

Failure to collect outcome data in randomised trials can result in bias and loss of statistical power. Further evaluations of strategies to increase retention are required. We assessed the effectiveness of two strategies for retention in a randomised prevention trial using a two-by-two factorial randomised study within a trial (SWAT).

Methods

Parents of babies included in the host trial were randomised to (1) short message service (SMS) notification prior to sending questionnaires at 3, 6, 12 and 18 months versus no SMS notification and (2) a £10 voucher sent with the invitation letter for the primary follow-up visit at 24 months or given at the visit. The two co-primary outcomes were collection of host trial (1) questionnaire data at interim follow-up times and (2) primary outcome at 24 months during a home/clinic visit with a research nurse.

Results

Between November 2014 and November 2016, 1394 participants were randomised: 350 to no SMS + voucher at visit, 345 to SMS + voucher at visit, 352 to no SMS + voucher before visit and 347 to SMS + voucher before visit. Overall questionnaire data was collected at interim follow-up times for 75% in both the group allocated to the prior SMS notification and the group allocated to no SMS notification (odds ratio (OR) SMS versus none 1.02, 95% CI 0.83 to 1.25). Host trial primary outcome data was collected at a visit for 557 (80%) allocated to the voucher before the visit in the invitation letter and for 566 (81%) whose parents were allocated to receive the voucher at the visit (OR before versus at visit 0.89, 95% CI 0.69 to 1.17).

Conclusion

There was no evidence of a difference in retention according to SMS notification or voucher timing. Future synthesis of SWAT results is required to be able to detect small but important incremental effects of retention strategies.

Trial registration

ISRCTN registry, ID: ISRCTN21528841. Registered on 25 July 2014. SWAT Repository Store ID 25.
Using systematic data categorisation to quantify the types of data collected in clinical trials: the DataCat project
Authors: Crowley Evelyn , Treweek Shaun , Banister Katie , Breeman Suzanne , Constable Lynda , Cotton Seonaidh , Duncan Anne , El Feky Adel , Gardner Heidi , Goodman Kirsteen , Lanz Doris , McDonald Alison , Ogburn Emma , Starr Kath , Stevens Natasha , Valente Marie , Fernie Gordon
Published: June 2020

Background

Data collection consumes a large proportion of clinical trial resources. Each data item requires time and effort for collection, processing and quality control procedures. In general, more data equals a heavier burden for trial staff and participants. It is also likely to increase costs. Knowing the types of data being collected, and in what proportion, will be helpful to ensure that limited trial resources and participant goodwill are used wisely.

Aim

The aim of this study is to categorise the types of data collected across a broad range of trials and assess what proportion of collected data each category represents.

Methods

We developed a standard operating procedure to categorise data into primary outcome, secondary outcome and 15 other categories. We categorised all variables collected on trial data collection forms from 18, mainly publicly funded, randomised superiority trials, including trials of an investigational medicinal product and complex interventions. Categorisation was done independently in pairs: one person having in-depth knowledge of the trial, the other independent of the trial. Disagreement was resolved through reference to the trial protocol and discussion, with the project team being consulted if necessary.

Key results

Primary outcome data accounted for 5.0% (median)/11.2% (mean) of all data items collected. Secondary outcomes accounted for 39.9% (median)/42.5% (mean) of all data items. Non-outcome data such as participant identifiers and demographic data represented 32.4% (median)/36.5% (mean) of all data items collected.

Conclusion

A small proportion of the data collected in our sample of 18 trials was related to the primary outcome. Secondary outcomes accounted for eight times the volume of data as the primary outcome. A substantial amount of data collection is not related to trial outcomes. Trialists should work to make sure that the data they collect are only those essential to support the health and treatment decisions of those whom the trial is designed to inform.
Impact of routine assessment of health-related quality of life coupled with therapeutic information on compliance with endocrine therapy in patients with non-metastatic breast cancer: protocol for a randomized controlled trial
Authors: Mamguem Kamga Ariane , Di Martino Cyril , Anota Amelie , Paget-Bailly Sophie , Coutant Charles , Arveux Patrick , Desmoulins Isabelle , Dabakuyo-Yonli Tienhan Sandrine
Published: June 2020

Background

Despite its proven efficacy in reducing recurrence and improving survival, adherence to endocrine therapy (ET) is suboptimal in women with breast cancer (BC). Health-related quality of life (HRQoL) in BC has been widely studied and many positive effects have been highlighted. Recently, a link between HRQoL and compliance with ET has been suggested, which would suggest a potential role for HRQoL assessment in improving compliance with ET. With the advent of digital technologies, electronic collection of HRQoL on a tablet is now possible. Thus, we hypothesize that systematic HRQoL assessment (using a tablet, prior to each consultation, with presentation of scores to clinicians) coupled with therapeutic information could have an impact on 12-month compliance with ET in patients with non-metastatic BC.

Methods

In this study, we will include 342 women with non-metastatic hormone receptor–positive BC with an indication for treatment with ET. Patients will be randomly assigned 1:1 by minimization and stratified by age, stage, type of ET prescribed, and presence of comorbidities (or not) in two arms. The intervention will consist of numerical HRQoL assessment using the CHES (Computer-based Health Evaluation System) software before each consultation (with delivery of scores to clinicians) coupled with therapeutic information. Therapeutic information will consist of three workshops related to understanding the prescription, nutrition, and fatigue. A reminder letter will be sent to patients every month. Patients in the control group will follow standard care. HRQoL will be assessed using a classic “paper-pencil” collection at baseline in both arms to ensure comparability between arms and at 12 months. The primary endpoint is 12-month compliance with ET. Patient satisfaction with care and the clinicians’ perception of the usefulness of routine HRQoL assessment will also be assessed.

Discussion

This study will allow clinicians to identify and better understand the areas in which patients who receive ET have difficulties and thus it will assist clinicians with patient management. Systematic evaluation of HRQoL could provide an additional endpoint for measuring patients’ health status and treatment-related symptoms, including ET. If the results of this study are positive, this intervention could be proposed as an integral part of daily clinical practice in patients who receive ET.

Trial registration

ClinicalTrials.govNCT04176809. Registered Nov. 25, 2019.
Using targeting to recruit men and women of color into a behavioral weight loss trial
Authors: Crane Melissa M. , Seburg Elisabeth M. , Levy Rona L. , Jeffery Robert W. , Sherwood Nancy E.
Published: June 2020

Background

The majority of participants in weight loss trials are non-Hispanic White women, while men and women of color are underrepresented. This study presents data obtained from non-targeted and targeted recruitment approaches in a trial of behavioral weight loss programs to (1) describe the yields from each approach and (2) compare the demographics, weight control histories, and study involvement of samples recruited by each approach.

Methods

Data for this observational study include source of recruitment, demographic information, weight loss experiences (e.g., lifetime weight loss, current weight loss behaviors), and completion of the 6-month assessment visit.

Results

Men comprised 14.2% of participants who responded to non-targeted recruitment efforts, while targeted efforts yielded 50.4% men. Similarly, people of color comprised 12.8% of those who responded to non-targeted approaches, whereas targeted recruitment methods yielded 47.2% people of color. Men recruited through targeted methods were younger (p = 0.01) than men recruited through non-targeted means but were otherwise similar. Women of color recruited through targeted methods reported use of fewer weight loss strategies relative to women of color recruited through non-targeted means (p = 0.006) but were otherwise similar. There were no differences by recruitment method on retention to the study.

Conclusions

Using targeted recruitment methods increased the ethnic and gender diversity of the recruited sample without reducing study retention. This targeting also increased the enrollment of women with less weight loss experience who may not have otherwise sought out a weight loss program. Developing and implementing a targeted recruitment plan should be considered early in the clinical trial development process.

Trial registration

Clinicaltrials.gov, NCT02368002. Registered on 20 February 2015.