bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-lapse angiography of the ocular fundus: a new video-angiography
Authors: Gu Chufeng , Chen Jili , Su Tong , Qiu Qinghua
Published: December 2019

Background

Ocular fundus angiography is an indispensable component of the tests utilized for fundus diseases. Dynamic angiography results can provide additional information; however, many difficulties remain. In this study, we introduce a modified method, time-lapse angiography (TLA), to dynamically present imaging results.

Methods

TLA, combining time-lapse photography and fundus angiography (using Heidelberg retina angiography II, Germany), includes pre-photographing and post- photosynthesis and ultimately produces a video that is approximately 15 s in length.

Results

Four typical videos in the article showed the characteristics of TLA, including a short and rapid but continuous and integral presentation, highly valid information, high definition, etc.

Conclusions

TLA is beneficial for the diagnosis of diseases and the assessment of progression and is convenient for peer communication, patient interpretation, and student education. The application of time-lapse photography in ocular fundus angiography is a monumental and innovative attempt.
Fertility-sparing surgery and oncologic outcome among patients with early-stage ovarian cancer ~propensity score- matched analysis~
Authors: Kajiyama Hiroaki , Suzuki Shiro , Yoshikawa Nobuhisa , Kawai Michiyasu , Mizuno Kimio , Yamamuro Osamu , Nagasaka Tetsuro , Shibata Kiyosumi , Kikkawa Fumitaka
Published: December 2019

Background

The aim of this study was to investigate how much the risks of recurrence and death are increased as a consequence of selecting fertility-sparing surgery (FSS) in young women with epithelial ovarian cancer (EOC).

Methods

After a central pathological review and search of the medical records from 14 collaborating hospitals, a non-randomized, observational cohort study was conducted between 1987 and 2015, including 1183 women with stage I EOC. Finally, a total of 285 patients with stage I EOC at reproductive age were recruited. Oncologic outcomes were compared between the FSS (N = 101) and radical surgery (RS) group (N = 184) using a propensity score (PS)-matching technique to adjust for relevant risk factors: the age, substage, histological type, grade, CA125 values, ascites cytology, ascites volume, and chemotherapy.

Results

During 66.0 months (median) of follow-up, 42 patients (14.7%) developed recurrence, and 31 patients (10.9%) died. In the original cohort, there was no significant difference in overall survival (OS) or recurrence-free survival (RFS) between the FSS and RS groups {Log-rank: OS (P = 0.838), RFS (P = 0.377)}. In the PS-matched cohort after adjustment for multiple clinicopathologic factors, there was no significant difference in RFS or OS between the FSS and RS groups {RFS (FSS vs. RS), HR: 1.262 (95% CI: 0.559–2.852), P = 0. 575; OS (FSS vs. RS), HR: 1.206 (95% CI: 0.460–3.163), P = 0.704}.

Conclusions

After adjustment for clinicopathologic factors, FSS in itself may not worsen the oncologic outcome in young women with early-stage EOC. A large-scale clinical study is necessary to validate the findings.
Systemic reaction to and interference with urine protein measurements after intravenous fluorescein injection
Authors: Bouman Annemieke Clementine , de Kruijf Damaris , Emmen Judith Maria Antonia , Rettig Thijs Clemens David , Groot Maria Jolande Charlotte Kooijman-de , Faes Miriam Christina
Published: December 2019

Background

Fluorescein angiography is an important and frequently used diagnostic tool in ophthalmological practice. In this case report we describe a patient who experienced an anaphylactic reaction after the injection of fluorescein. Furthermore, we report an interference with laboratory testing by fluorescein in this patient and summarize the literature on this topic.

Case presentation

An 86-year old Caucasian woman undergoing fluorescein angiography due to suspected peripapillary neovascularizations collapsed after the injection of fluorescein. The patient developed an anaphylactic reaction. With fluid resuscitation and oxygen therapy, the patient regained consciousness after a few minutes. The patient was admitted to the geriatric ward for observation, and routine blood and urine tests were performed. Urine protein concentration appeared to be falsely increased as a consequence of disturbance of the laboratory analysis by the presence of fluorescein.

Conclusions

Serious complications can occur with fluorescein angiography, such as an anaphylactic reaction. In the case of anaphylaxis appropriate supportive measures including the use of oxygen and epinephrine (e.g. EpiPen), should be available to prevent morbidity and mortality from this test. Furthermore, these potential complications should be taken into consideration when choosing the healthcare setting for fluorescein angiography, such as the immediate availability of an acute medical team.

Several studies have demonstrated the interference of laboratory analyses by fluorescein. The majority of these studies were published 10 to 30 years ago. By presenting this case, the authors hope to bring renewed attention to this phenomenon among clinicians, as falsely increased or decreased laboratory values can result in unnecessary diagnostics and/or therapy.
Participation factors for asthma education programs - a cross sectional survey
Authors: Atmann Oxana , Linde Klaus , Werner Christoph , Dorn Ulrike , Schneider Antonius
Published: December 2019

Background

Although the impact of asthma education on important outcomes (e.g. emergency visits) has been well established, only an estimated quarter of asthma patients in Germany have received patient education yet. The aim of the study was to identify patient factors that could increase participation in asthma education programs.

Methods

This cross-sectional study investigated participation factors and differences between trained (n = 64) and untrained (n = 65) asthma patients from a large outpatient center in Germany. The survey included answers to asthma-related questions and open questions on patient education as well as such about knowledge of health literacy and eHealth.

Results

Mean age of participants was 55 ± 19 years and 61% were female. Trained patients were more likely to participate in disease management programs (odds ratio (OR) 6.85; 95%CI 2.17–21.59), were more frequently non-smokers (OR 0.07; 95%CI 0.01–0.85) and more often had an asthma action plan (OR 20.2; 1.55–263.41). Open questions’ analysis of untrained asthma patients revealed that patients felt they were not adequately informed about asthma education (37%). About one-third of all patients (27%) showed openness to online asthma education. Analysis of HL and eHealth showed no difference between the groups.

Conclusion

Untrained asthma patients should be informed even more intensively by their physicians about the importance and value of asthma education. Asthma education does not seem to benefit patients’ health literacy. Online asthma education is of interest to approximately one-third of asthma patients. This should be motivation to develop and implement online asthma education concepts.
Can clinical ethics committees be legitimate actors in bedside rationing?
Authors: Magelssen Morten , Bærøe Kristine
Published: December 2019

Background

Rationing and allocation decisions at the clinical level – bedside rationing – entail complex dilemmas that clinicians and managers often find difficult to handle. There is a lack of mechanisms and aids for promoting fair decisions, especially in hard cases. Reports indicate that clinical ethics committees (CECs) sometimes handle cases that involve bedside rationing dilemmas. Can CECs have a legitimate role to play in bedside rationing?

Main text

Aided by two frameworks for legitimate priority setting, we discuss how CECs can contribute to enhanced epistemic, procedural and political legitimacy in bedside rationing decisions. Drawing on previous work we present brief case vignettes and outline several potential roles that CECs may play, and then discuss whether these might contribute to rationing decisions becoming legitimate. In the process, key prerequisites for such legitimacy are identified. Legitimacy places demands on aspects such as the CEC’s deliberation process, the involvement of stakeholders, transparency of process, the opportunity to appeal decisions, and the competence of CEC members. On these conditions, CECs can help strengthen the legitimacy of some of the rationing decisions clinicians and managers have to make.

Conclusions

On specified conditions, CECs can have a well-justified advisory role to play in order to enhance the legitimacy of bedside rationing decisions.
Statistical and spectral analysis of ECG signal towards achieving non-invasive blood glucose monitoring
Authors: Tobore Igbe , Li Jingzhen , Kandwal Abhishek , Yuhang Liu , Nie Zedong , Wang Lei
Published: December 2019

Background

Globally, the cases of diabetes mellitus (diabetes) have increased in the past three decades, and it is recorded as one of the leading cause of death. This epidemic is a metabolic condition where the body cannot regulate blood glucose, thereby leading to abnormally high blood sugar. Genetic condition plays a significant role to determine a person susceptibility to the condition, a sedentary lifestyle and an unhealthy diet are behaviour that supports the current global epidemic. The complication that arises from diabetes includes loss of vision, peripheral neuropathy, cardiovascular complications and so on. Victims of this condition require constant monitoring of blood glucose which is done by the pricking of the finger. This procedure is painful, inconvenient and can lead to disease infection. Therefore, it is important to find a way to measure blood glucose non-invasively to minimize or eliminate the disadvantages encountered with the usual monitoring of blood glucose.

Method

In this paper, we performed two experiments on 16 participants while electrocardiogram (ECG) data was continuously captured. In the first experiment, participants are required to consume 75 g of anhydrous glucose solution (oral glucose tolerance test) and the second experiment, no glucose solution was taken. We explored statistical and spectral analysis on HRV, HR, R-H, P-H, PRQ, QRS, QT, QTC and ST segments derived from ECG signal to investigate which segments should be considered for the possibility of achieving non-invasive blood glucose monitoring. In the statistical analysis, we examined the pattern of the data with the boxplot technique to reveal the change in the statistical properties of the data. Power spectral density estimation was adopted for the spectral analysis to show the frequency distribution of the data.

Results

HRV segment obtained a statistical score of 81% for decreasing pattern and HR segment have the same statistical score for increasing pattern among the participants in the first quartile, median and mean properties. While ST segment has a statistical score of 81% for decreasing pattern in the third quartile, QT segment has 81% for increasing pattern for the median. From a total change score of 6, ST, QT, PRQ, P-H, HR and HRV obtained 4, 5, 4, 5 and 6 respectively. For spectral analysis, HRV and HR segment scored 81 and 75% respectively. ST, QT, PRQ have 75, 62 and 68% respectively.

Conclusions

The results obtained demonstrate that HR, HRV, PRQ, QT and ST segments under a normal, healthy condition are affected by glucose and should be considered for modelling a system to achieve the possibility of non-invasive blood glucose measurement with ECG.
Inter/intra-frame constrained vascular segmentation in X-ray angiographic image sequence
Authors: Song Shuang , Du Chenbing , Chen Ying , Ai Danni , Song Hong , Huang Yong , Wang Yongtian , Yang Jian
Published: December 2019

Background

Automatic vascular segmentation in X-ray angiographic image sequence is of crucial interest, for instance, for better quantifying coronary arteries in diagnostic and interventional procedures.

Methods

A novel inter/intra-frame constrained vascular segmentation method is proposed to automatically segment vessels in coronary X-ray angiographic image sequence. First, a morphological filter operator is applied to remove structures undergoing the respiratory motion from the original image sequence. Second, an inter-frame constrained robust principal component analysis (RPCA) is utilized to remove the quasi-static structures from the image sequence. Third, an intra-frame constrained RPCA is employed to smooth the final extracted vascular sequence. Fourth, a multi-feature fusion is designed to improve the vascular contrast and the final vascular segmentation is realized by thresholding-based method.

Results

Experiments are conducted on 22 clinical X-ray angiographic image sequences. The global and local contrast-to-noise ratio of the proposed method are 6.6344 and 4.2882, respectively. And the precision, sensitivity and F1 value are 0.7378, 0.7960 and 0.7658, respectively. It demonstrates that our method is effective and robust for vascular segmentation from image sequence.

Conclusions

The proposed method is effective to remove non-vascular structures, reduce motion artefacts and other non-uniform illumination caused noises. Also, the proposed method is online which can just process one image per time without re-optimizing the model.
Influencing factors of physicians’ prescription behavior in selecting essential medicines: a cross-sectional survey in Chinese county hospitals
Authors: Zhou Xin , Zhang Xueting , Yang Linsheng , Hu Xu , Shen Aizong , Huang Xiaohui , Xie Xuefeng
Published: December 2019

Background

To explore the key factors affecting prescription practices of essential medicines in Chinese county hospital. National essential medicine policy (NEMP) plays important roles in health care system, especially in developing countries. As a fundamental component in the Chinese health system reform, NEMP was implemented in primary health care institutions during the first stage of reform. As it is rolled out, priority usage and zero-mark-up policy of essential medicines are to be applied in every government-run healthcare institution. However, the intention and influence factors of physicians on priority selecting essential medicine remains unclear.

Methods

Based on the theory of planned behavior, a cross-sectional questionnaire survey was conducted to analyze physicians’ intention, attitude, subjective norms (SNs) and perceived behavioral control (PBC) on prescrictions and their actual behavior on selection of essential medicines.

Results

Two hundred eighty-two physicians participated in the structural questionnaire interview. The final structural equation model reflected influencing factors affecting physicians’ prescribing behavior (χ2/df = 1.32, GFI = 0.99, IFI = 0.99). Structural equation model analysis showed that attitude, other influencers and institutional environment, and PBC significantly affected behavioral intention. However, the control extent of cognition behavior of physicians prescribing had no significant positive effect on the priority usage of essential medicines.

Conclusion

Investigation results demonstrate physicians are unaware of NEMP design and implementation plans. To help enhance rational use of essential medicines we suggest educating physicians on the value of NEMP, and integrating the drug shortage report into the essential medicine (EM) bidding system seamless communication with pharmaceutical manufacturers’ credit information system.
Explaining the successes and failures of tuberculosis treatment programs; a tale of two regions in rural eastern Uganda
Authors: Izudi Jonathan , Tamwesigire Imelda. K. , Bajunirwe Francis
Published: December 2019

Background

Optimally performing tuberculosis (TB) programs are characterized by treatment success rate (TSR) of at least 90%. In rural eastern Uganda, and elsewhere in sub Saharan Africa, TSR varies considerably across district TB programs and the reasons for the differences are unclear. This study explored factors associated with the low and high TSR across four districts in rural eastern Uganda.

Methods

We interviewed District TB and Leprosy Supervisors, Laboratory focal persons, and health facility TB focal persons from four districts in eastern Uganda as key informants. Interviews were audio recorded, transcribed verbatim, and imported into ATLAs.ti where thematic content analysis was performed and results were summarized into themes.

Results

The emerging themes were categorized as either facilitators of or barriers to treatment success. The emerging facilitators prevailing in the districts with high rates of treatment success were using data to make decisions and design interventions, continuous quality improvement, capacity building, and prioritization of better management of people with TB. The barriers common in districts with low rates of treatment success included lack of motivated and dedicated TB focal persons, scarce or no funding for implementing TB activities, and a poor implementation of community-based directly observed therapy short course.

Conclusion

This study shows that several factors are associated with the differing rates of treatment success in rural eastern Uganda. These factors should be the focus for TB control programs in Uganda and similar settings in order to improve rates of treatment success.
Sequence analysis and variant identification at the APOC3 gene locus indicates association of rs5218 with BMI in a sample of Kuwaiti’s
Authors: Malalla Zainab H. , Al-Serri Ahmad E. , AlAskar Huda M. , Al-Kandari Wafaa Y. , Al-Bustan Suzanne A.
Published: December 2019

Background

APOC3 is important in lipid transport and metabolism with limited studies reporting genetic sequence variations in specific ethnic groups. The present study aimed to analyze the fullAPOC3sequence among Kuwaiti Arabs and test the association of selected variants with lipid levels and BMI.

Methods

Variants were identified by Sanger sequencing the entireAPOC3gene in 100 Kuwaiti Arabs. Variants and their genotypes were fully characterized and used to construct haplotype blocks. Four variants (rs5128, rs2854117, rs2070668, KUAPOC3N3 g.5196 A > G) were selected for testing association with serum lipid levels and BMI in a cohort (n = 733).

Results

APOC3sequence (4.3 kb) of a Kuwaiti Arab was deposited in Genbank (accession number KJ437193). Forty-two variants including 3 novels were identified including an “A” insertion at genomic positions 116,700,599–116,700,600 (promoter region) and two substitutions in intron 1 at genomic positions 116,700,819 and 116,701,159. Only three variants, (rs5128, rs2854117, and rs2070668) were analyzed for association of which rs5128 showed a trend for association with increased BMI, TG and VLDL levels that was further investigated using multivariate analysis. A significant association of rs5128 with BMI (p <  0.05) was observed following a dominant genetic model with increased risk by an OR of 4.022 (CI: 1.13–14.30).

Conclusion

The present study is the first to report sequence analysis ofAPOC3in an Arab ethnic group. This study supports the inclusion of rs5128 as a marker for assessing genetic risk to dyslipidemia and obesity and the inclusion of the novel variant g.5196 A > G for population stratification of Arabs.
Outcome preferences of older people with multiple chronic conditions and hypertension: a cross-sectional survey using best-worst scaling
Authors: Aschmann Hélène E. , Puhan Milo A. , Robbins Craig W. , Bayliss Elizabeth A. , Chan Wiley V. , Mularski Richard A. , Wilson Renée F. , Bennett Wendy L. , Sheehan Orla C. , Yu Tsung , Yebyo Henock G. , Leff Bruce , Tabano Heather , Armacost Karen , Glover Carol , Maslow Katie , Mintz Suzanne , Boyd Cynthia M.
Published: December 2019

Background

Older people with hypertension and multiple chronic conditions (MCC) receive complex treatments and face challenging trade-offs. Patients’ preferences for different health outcomes can impact multiple treatment decisions. Since evidence about outcome preferences is especially scarce among people with MCC our aim was to elicit preferences of people with MCC for outcomes related to hypertension, and to determine how these outcomes should be weighed when benefits and harms are assessed for patient-centered clinical practice guidelines and health economic assessments.

Methods

We sent a best-worst scaling preference survey to a random sample identified from a primary care network of Kaiser Permanente (Colorado, USA). The sample included individuals age 60 or greater with hypertension and at least two other chronic conditions. We assessed average ranking of patient-important outcomes using conditional logit regression (stroke, heart attack, heart failure, dialysis, cognitive impairment, chronic kidney disease, acute kidney injury, fainting, injurious falls, low blood pressure with dizziness, treatment burden) and studied variation across individuals.

Results

Of 450 invited participants, 217 (48%) completed the survey, and we excluded 10 respondents who had more than two missing choices, resulting in a final sample of 207 respondents. Participants ranked stroke as the most worrisome outcome and treatment burden as the least worrisome outcome (conditional logit parameters: 3.19 (standard error 0.09) for stroke, 0 for treatment burden). None of the outcomes were always chosen as the most or least worrisome by more than 25% of respondents, indicating that all outcomes were somewhat worrisome to respondents. Predefined subgroup analyses according to age, self-reported life-expectancy, degree of comorbidity, number of medications and antihypertensive treatment did not reveal meaningful differences.

Conclusions

Although some outcomes were more worrisome to patients than others, our results indicate that none of the outcomes should be disregarded for clinical practice guidelines and health economic assessments.
The prognostic capacities of CBP and p300 in locally advanced rectal cancer
Authors: Rühlmann Felix , Windhof-Jaidhauser Indra Maria , Menze Cornelius , Beißbarth Tim , Bohnenberger Hanibal , Ghadimi Michael , Dango Sebastian
Published: December 2019

Background

CREB-binding protein (CBP) and p300 represent histone acetyltransferases (HATs) and transcriptional coactivators that play essential roles in tumour initiation and progression. Both proteins are generally thought to function as tumour suppressors, although their distinct roles in colorectal cancer (CRC) remain inconsistent and ambiguous.

Thus, we analysed the expression of these two HATs in human tissue samples from patients with locally advanced rectal cancer via immunohistochemistry and evaluated their potential impacts on future CRC diagnosis and treatment.

Methods

In our analysis, we included ninety-three (n = 93) patients diagnosed with adenocarcinoma in the upper third of the rectum. None of the patients received preoperative chemoradiotherapy, but the patients did undergo primary resection of the tumour within the phase II GAST-05 trial. By using H-scores, the expression of both proteins was visualised via immunohistochemistry in resected specimens from the patients. CBP and p300 expression were correlated with clinical and follow-up data.

Results

Our analysis showed that high expression of CBP was significantly associated with prolonged cancer-specific survival (CSS;p = 0.002). In univariate analysis, CBP was an independent prognostic parameter for CSS (p = 0.042). High nuclear CBP expression was observed in two-thirds of patients. In contrast, we could not find any significant correlation between the expression of p300 and cancer-specific survival in this cohort of patients (p = 0.09). We did not observe any cooperation between CBP and p300 in our analysis.

Conclusions

High expression of CBP was significantly associated with improved oncological outcomes. This finding could help to stratify patients in the future for CRC treatment. Histone deacetylase (HDAC) inhibitors are increasingly playing a role in oncological treatment and could additionally become therapeutic options in CRC. Our findings need to be further evaluated and verified in future clinical analyses.
A live-cell imaging system for visualizing the transport of Marburg virus nucleocapsid-like structures
Authors: Takamatsu Yuki , Dolnik Olga , Noda Takeshi , Becker Stephan
Published: December 2019

Background

Live-cell imaging is a powerful tool for visualization of the spatio-temporal dynamics of moving signals in living cells. Although this technique can be utilized to visualize nucleocapsid transport in Marburg virus (MARV)- or Ebola virus-infected cells, the experiments require biosafety level-4 (BSL-4) laboratories, which are restricted to trained and authorized individuals.

Methods

To overcome this limitation, we developed a live-cell imaging system to visualize MARV nucleocapsid-like structures using fluorescence-conjugated viral proteins, which can be conducted outside BSL-4 laboratories.

Results

Our experiments revealed that nucleocapsid-like structures have similar transport characteristics to those of nucleocapsids observed in MARV-infected cells, both of which are mediated by actin polymerization.

Conclusions

We developed a non-infectious live cell imaging system to visualize intracellular transport of MARV nucleocapsid-like structures. This system provides a safe platform to evaluate antiviral drugs that inhibit MARV nucleocapsid transport.
Sustainment, Sustainability, and Spread Study (SSaSSy): protocol for a study of factors that contribute to the sustainment, sustainability, and spread of practice changes introduced through an evidence-based quality-improvement intervention in Canadian nursing homes
Authors: Berta Whitney B. , Wagg Adrian , Cranley Lisa , Doupe Malcolm B. , Ginsburg Liane , Hoben Matthias , MacEachern Lauren , Chamberlain Stephanie , Clement Fiona , Easterbrook Adam , Keefe Janice M. , Knopp-Sihota Jennifer , Rappon Tim , Reid Colin , Song Yuting , Estabrooks Carole A.
Published: December 2019

Background

Implementation scientists and practitioners, alike, recognize the importance of sustaining practice change, however post-implementation studies of interventions are rare. This is a protocol for the Sustainment, Sustainability and Spread Study (SSaSSy). The purpose of this study is to contribute to knowledge on the sustainment (sustained use), sustainability (sustained benefits), and spread of evidence-based practice innovations in health care. Specifically, this is apost-implementationstudy of an evidence-informed, Care Aide-led, facilitation-based quality-improvement intervention called SCOPE (Safer Care for Older Persons (in long-term care) Environments). SCOPE has been implemented in nursing homes in the Canadian Provinces of Manitoba (MB), Alberta (AB) and British Columbia (BC). Our study has three aims: (i) to determine the role that adaptation/contextualization plays in sustainment, sustainability and spread of the SCOPE intervention; (ii) to study the relative effects on sustainment, sustainability and intra-organizational spread of high-intensity and low-intensity post-implementation “boosters”, and a “no booster” condition, and (iii) to compare the relative costs and impacts of each booster condition.

Methods/design

SSaSSy is a two-phase mixed methods study. The overarching design is convergent, with qualitative and quantitative data collected over a similar timeframe in each of the two phases, analyzed independently, then merged for analysis and interpretation. Phase 1 is a pilot involving up to 7 units in 7 MB nursing homes in which SCOPE was piloted in 2016 to 2017, in preparation for phase 2. Phase 2 will comprise a quasi-experiment with two treatment groups of low- and high-intensity post-implementation “boosters”, and an untreated control group (no booster), using pretests and post-tests of the dependent variables relating to sustained care and management practices, and resident outcomes. Phase 2 will involve 31 trial sites in BC (17 units) and AB (14 units) nursing homes, where the SCOPE trial concluded in May 2019.

Discussion

This project stands to advance understanding of the factors that influence the sustainment of practice changes introduced through evidence-informed practice change interventions, and their associated sustainability. Findings will inform our understanding of the nature of the relationship of fidelity and adaptation to sustainment and sustainability, and afford insights into factors that influence the intra-organizational spread of practice changes introduced through complex interventions.
A hybrid automated treatment planning solution for esophageal cancer
Authors: Ling Chifang , Han Xu , Zhai Peng , Xu Hao , Chen Jiayan , Wang Jiazhou , Hu Weigang
Published: December 2019

Objective

This study aims to investigate a hybrid automated treatment planning (HAP) solution that combines knowledge-based planning (KBP) and script-based planning for esophageal cancer.

Methods

In order to fully investigate the advantages of HAP, three planning strategies were implemented in the present study: HAP, KBP, and full manual planning. Each method was applied to 20 patients. For HAP and KBP, the objective functions for plan optimization were generated from a dose–volume histogram (DVH) estimation model, which was based on 70 esophageal patients. Script-based automated planning was used for HAP, while the regular IMRT inverse planning method was used for KBP. For full manual planning, clinical standards were applied to create the plans. Paired t-tests were performed to compare the differences in dose-volume indices among the three planning methods.

Results

Among the three planning strategies, HAP exhibited the best performance in all dose-volume indices, except for PTV dose homogeneity and lung V5. PTV conformity and spinal cord sparing were significantly improved in HAP (P < 0.001). Compared to KBP, HAP improved all indices, except for lung V5. Furthermore, the OAR sparing and target coverage between HAP and full manual planning were similar. Moreover, HAP had the shortest average planning time (57 min), when compared to KBP (63 min) and full manual planning (118 min).

Conclusion

HAP is an effective planning strategy for obtaining a high quality treatment plan for esophageal cancer.
Reliability of synovial fluid alpha-defensin and leukocyte esterase in diagnosing periprosthetic joint infection (PJI): a systematic review and meta-analysis
Authors: Chen Yisheng , Kang Xueran , Tao Jie , Zhang Yunpeng , Ying Chenting , Lin Weiwei
Published: December 2019

Background

Synovial fluid proteins had been applied as diagnostic biomarkers for periprosthetic joint infection (PJI) in recent research papers. Thus, this meta-analysis aimed to estimate the diagnostic efficiency of synovial fluid α-defensin and leukocyte esterase (LE) for PJI.

Methods

We conducted our systematic review by searching the keywords in online databases such as PubMed, Embase, Cochrane, Elsevier, Springer, and Web of Science from the time of database inception to October 2018. Inclusion criteria were as follows: patients who have undergone knee, hip, or shoulder joint replacements; α-defensin or leukocyte esterase (LE strip) of synovial fluid was detected as the biomarker for PJI diagnosis; and Musculoskeletal Infection Society (MSIS) or utilizing a combination of clinical data was considered as the gold standard. Diagnostic parameters including sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary of receiver operating characteristics curve (AUSROC) were calculated for the included studies to evaluate the synovial fluid α-defensin and LE for PJI diagnosis.

Results

After full-text review, 28 studies were qualified for this systematic review, 16 studies used α-defensin and the other 12 were conducted using LE strip. The pooled sensitivity, specificity, and DOR of LE strip were 87% (95% CI 84–90%), 96% (95% CI 95–97%), and 170.09 (95% CI 97.63–296.32), respectively, while the pooled sensitivity, specificity, and DOR of α-defensin were 87% (95% CI 83–90%), 97% (95% CI 96–98%), and 158.18 (95% CI 74.26–336.91), respectively. The AUSROC for LE strip and α-defensin were 0.9818 and 0.9685, respectively.

Conclusion

Both LE strip and α-defensin of synovial fluid provide rapid and convenient diagnosis for PJI. Sensitivity of α-defensin and LE strip are the same, while both these two methods have high specificity in clinical practice.
Mandibuloacral dysplasia type B (MADB): a cohort of eight patients from Suriname with a homozygous founder mutation in ZMPSTE24 (FACE1), clinical diagnostic criteria and management guidelines
Authors: Hitzert M. M. , van der Crabben S. N. , Baldewsingh G. , van Amstel H. K. Ploos , van den Wijngaard A. , van Ravenswaaij-Arts C. M. A. , Zijlmans C. W. R.
Published: December 2019

Background

Mandibuloacral Dysplasia with type B lipodystrophy (MADB) is a rare premature aging disorder with an autosomal recessive inheritance pattern. MADB is characterized by brittle hair, mottled, atrophic skin, generalized lipodystrophy, insulin resistance, metabolic complications and skeletal features like stunted growth, mandibular and clavicular hypoplasia and acro-osteolysis of the distal phalanges. MADB is caused by reduced activity of the enzyme zinc metalloprotease ZMPSTE24 resulting from compound heterozygous or homozygous mutations in ZMPSTE24.

Methods

In 2012, and again in 2018, eight related patients from the remote tropical rainforest of inland Suriname were analysed for dysmorphic features. DNA analysis was performed and clinical features were documented. We also analysed all previously reported genetically confirmed MADB patients from literature (n = 12) for their clinical features. Based on the features of all cases (n = 20) we defined major criteria as those present in 85–100% of all MADB patients and minor criteria as those present in 70–84% of patients.

Results

All the Surinamese patients are of African descent and share the same homozygous c.1196A > G, p.(Tyr399Cys) missense variant in the ZMPSTE24 gene, confirming MADB. Major criteria were found to be: short stature, clavicular hypoplasia, delayed closure of cranial sutures, high palate, mandibular hypoplasia, dental crowding, acro-osteolysis of the distal phalanges, hypoplastic nails, brittle and/or sparse hair, mottled pigmentation, atrophic and sclerodermic skin, and calcified skin nodules. Minor criteria were (generalized or partial) lipoatrophy of the extremities, joint contractures and shortened phalanges. Based on our detailed clinical observations, and a review of previously described cases, we propose that the clinical diagnosis of MADB is highly likely if a patient exhibits ≥4 major clinical criteria OR ≥ 3 major clinical criteria and ≥ 2 minor clinical criteria.

Conclusions

We report on eight related Surinamese patients with MADB due to a homozygous founder mutation in ZMPSTE24. In low-income countries laboratory facilities for molecular genetic testing are scarce or lacking. However, because diagnosing MADB is essential for guiding clinical management and for family counselling, we defined clinical diagnostic criteria and suggest management guidelines.
Detailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants
Authors: Hansen Mathias Lühr , Pellicer Adelina , Gluud Christian , Dempsey Eugene , Mintzer Jonathan , Hyttel-Sorensen Simon , Heuchan Anne Marie , Hagmann Cornelia , Dimitriou Gabriel , Pichler Gerhard , Naulaers Gunnar , Cheng Guoqiang , Vilan Ana , Tkaczyk Jakub , Kreutzer Karen B. , Fumagalli Monica , Claris Olivier , Fredly Siv , Szczapa Tomasz , Lange Theis , Jakobsen Janus Christian , Greisen Gorm
Published: December 2019

Background

Infants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by cerebral oxygenation monitoring versus treatment as usual. This article describes the detailed statistical analysis plan for the main publication, with the aim to prevent outcome reporting bias and data-driven analyses.

Methods/design

The SafeBoosC III trial is an investigator-initiated, randomised, multinational, pragmatic phase III trial with a parallel group structure, designed to investigate the benefits and harms of treatment based on cerebral near-infrared spectroscopy monitoring compared with treatment as usual. Randomisation will be 1:1 stratified for neonatal intensive care unit and gestational age (lower gestational age (< 26 weeks) compared to higher gestational age (≥ 26 weeks)). The primary outcome is a composite of death or severe brain injury at 36 weeks postmenstrual age. Primary analysis will be made on the intention-to-treat population for all outcomes, using mixed-model logistic regression adjusting for stratification variables. In the primary analysis, the twin intra-class correlation coefficient will not be considered. However, we will perform sensitivity analyses to address this. Our simulation study suggests that the inclusion of multiple births is unlikely to significantly affect our assessment of intervention effects, and therefore we have chosen the analysis where the twin intra-class correlation coefficient will not be considered as the primary analysis.

Discussion

In line with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines, we have developed and published this statistical analysis plan for the SafeBoosC III trial, prior to any data analysis.

Trial registration

ClinicalTrials.org, NCT03770741. Registered on 10 December 2018.
Typhoidal Salmonella human challenge studies: ethical and practical challenges and considerations for low-resource settings
Authors: Raymond Meriel , Gibani Malick M. , Day Nicholas P. J. , Cheah Phaik Yeong
Published: December 2019

Typhoidal Salmonella is a major global problem affecting more than 12 million people annually. Controlled human infection models (CHIMs) in high-resource settings have had an important role in accelerating the development of conjugate vaccines against Salmonella Typhi.

The typhoidal Salmonella model has an established safety profile in over 2000 volunteers in high-income settings, and trial protocols, with modification, could be readily transferred to new study sites. To date, a typhoidal Salmonella CHIM has not been conducted in a low-resource setting, although it is being considered.

Our article describes the challenges posed by a typhoidal Salmonella CHIM in the high-resource setting of Oxford and explores considerations for an endemic setting.

Development of CHIMs in endemic settings is scientifically justifiable as it remains unclear whether findings from challenge studies performed in high-resource non-endemic settings can be extrapolated to endemic settings, where the burden of invasive Salmonella is highest. Volunteers are likely to differ across a range of important variables such as previous Salmonella exposure, diet, intestinal microbiota, and genetic profile. CHIMs in endemic settings arguably are ethically justifiable as affected communities are more likely to gain benefit from the study. Local training and research capacity may be bolstered.

Safety was of primary importance in the Oxford model. Risk of harm to the individual was mitigated by careful inclusion and exclusion criteria; close monitoring with online diary and daily visits; 24/7 on-call staffing; and access to appropriate hospital facilities with capacity for in-patient admission. Risk of harm to the community was mitigated by exclusion of participants with contact with vulnerable persons; stringent hygiene and sanitation precautions; and demonstration of clearance of Salmonella infection from stool following antibiotic treatment.

Safety measures should be more stringent in settings where health systems, transport networks, and sanitation are less robust.

We compare the following issues between high- and low-resource settings: scientific justification, risk of harm to the individual and community, benefits to the individual and community, participant understanding, compensation, and regulatory requirements.

We conclude that, with careful consideration of country-specific ethical and practical issues, a typhoidal Salmonella CHIM in an endemic setting is possible.
Clinical outcome comparison of percutaneous coronary intervention and bypass surgery in diabetic patients with coronary artery disease: a meta-analysis of randomized controlled trials and observational studies
Authors: Zhai ChuanNan , Cong HongLiang , Hou Kai , Hu YueCheng , Zhang JingXia , Zhang YingYi
Published: December 2019

Background

The optimal revascularization technique in diabetic patients with complex coronary artery disease (CAD), including left main CAD and multivessel coronary disease (MVD), remains controversial. The current study aimed to compare adverse clinical endpoints of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM).

Methods

Relevant studies were found from MEDLINE, OVID, Science Direct, Embase and the Cochrane Central database from January 2010 to April 2019. Risk ratio (RR) with 95% confidence interval (CI) was used to express the pooled effect on discontinuous variables. Outcomes evaluated were all-cause mortality, major adverse cardiac/cerebrovascular events (MACCE), cardiac death, myocardial infarction, stroke, and repeat revascularization.

Results

Sixteen studies were included (18,224 patients). PCI was associated with the increase risk for MACCE (RR 1.59, 95% CI 1.38–1.85), cardiac death (RR 1.76, 95% CI 1.11–2.80), MI (RR 1.98, 95% CI 1.53–2.57), repeat revascularization (RR 2.61, 95% CI 2.08–3.29). The risks for all-cause mortality (RR 1.23, 95% CI 1.00–1.52) and stroke (RR 0.71, 95% CI 0.48–1.03) were similar between two strategies. Stratified analysis based on studies design and duration of follow-up showed largely similar findings with the overall analyses, except for a significant increased risk of all-cause mortality (RR 1.32, 95% CI 1.04–1.67) in long-term group, and CABG was associated with a higher stroke rate compared to PCI, which are results that were found in RCTs (RR 0.47, 95% CI 0.28–0.79) and mid-term groups (RR 0.39, 95% CI 0.23–0.66).

Conclusions

CABG was superior to PCI for diabetic patients with complex CAD (including left main CAD and/or MVD), but might be associated with a higher risk of stroke mid-term follow-up.

Number of Protocol registrationPROSPERO CRD 42019138505.
Dermatofibrosarcoma protuberans – the use of neoadjuvant imatinib for treatment of an uncommon breast malignancy: a case report
Authors: McGee Matthew W. , Boukhar Sarag A. , Monga Varun , Weigel Ronald , Phadke Sneha D.
Published: December 2019

Background

Dermatofibrosarcoma protuberans is a rare soft tissue malignancy that, if left untreated, can be locally destructive and life-threatening. Dermatofibrosarcoma protuberans is uncommon in the breast, and the similarity of its morphologic features with other spindle cell malignancies can make correct identification difficult. Immunohistochemistry and molecular testing can aid in the correct diagnosis when there is diagnostic uncertainty. Imatinib, a selective tyrosine kinase inhibitor, has been used for adjuvant treatment of dermatofibrosarcoma protuberans following surgical resection. When used as a neoadjuvant treatment, imatinib offers the opportunity to decrease tumor size prior to surgery to lessen the chance for disfigurement.

Case presentation

We present the case of a Caucasian woman who was 46-year-old when she first noted a mass in her right breast in 2015; she was initially diagnosed as having metaplastic breast carcinoma. Mastectomy and systemic chemotherapy were planned; however, after review of pathology at a referral center, the diagnosis was changed to dermatofibrosarcoma protuberans. She was treated with 4 months of neoadjuvant imatinib with adequate tumor shrinkage to perform breast conservation.

Conclusion

This patient’s case stresses the importance of correctly diagnosing this rare breast tumor through the histopathologic appearance of dermatofibrosarcoma protuberans, molecular pathogenesis, and immunohistochemistry. These techniques can help differentiate dermatofibrosarcoma protuberans from metaplastic breast carcinoma and other spindle cell lesions of the breast. This is critical, as the treatment options for metaplastic breast carcinoma significantly differ from treatment options for dermatofibrosarcoma protuberans. This case describes the use of imatinib as a neoadjuvant option to reduce preoperative tumor size and improve surgical outcomes.
Porcine rotavirus mainly infects primary porcine enterocytes at the basolateral surface
Authors: Cui Tingting , Theuns Sebastiaan , Xie Jiexiong , Nauwynck Hans J.
Published: December 2019

Intestinal epithelium functions as a barrier to protect multicellular organisms from the outside world. It consists of epithelial cells closely connected by intercellular junctions, selective gates which control paracellular diffusion of solutes, ions and macromolecules across the epithelium and keep out pathogens. Rotavirus is one of the major enteric viruses causing severe diarrhea in humans and animals. It specifically infects the enterocytes on villi of small intestines. The polarity of rotavirus replication in their target enterocytes and the role of intestinal epithelial integrity were examined in the present study. Treatment with EGTA, a drug that chelates calcium and disrupts the intercellular junctions, (i) significantly enhanced the infection of rotavirus in primary enterocytes, (ii) increased the binding of rotavirus to enterocytes, but (iii) considerably blocked internalization of rotavirus. After internalization, rotavirus was resistant to EGTA treatment. To investigate the polarity of rotavirus infection, the primary enterocytes were cultured in a transwell system and infected with rotavirus at either the apical or the basolateral surface. Rotavirus preferentially infected enterocytes at the basolateral surface. Restriction of infection through apical inoculation was overcome by EGTA treatment. Overall, our findings demonstrate that integrity of the intestinal epithelium is crucial in the host’s innate defense against rotavirus infection. In addition, the intercellular receptor is located basolaterally and disruption of intercellular junctions facilitates the binding of rotavirus to their receptor at the basolateral surface.
Hermite–Hadamard type inequalities for co-ordinated convex and qausi-convex functions and their applications
Authors: Latif Muhammad Amer , Rashid Saima , Dragomir Silvestru Sever , Chu Yu-Ming
Published: December 2019

In the article, we present several Hermite–Hadamard type inequalities for the co-ordinated convex and quasi-convex functions and give an application to the product of the moment of two continuous and independent random variables. Our results are generalizations of some earlier results. Additionally, an illustrative example on the probability distribution is given to support our results.