bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of two scores for short-term outcomes in patients with COPD exacerbation in the emergency department: the Ottawa COPD Risk Scale and the DECAF score
Authors: Unal Ali , Bayram Basak , Ergan Begum , Can Kazim , Ergun Yagiz Kagan , Kilinc Oguz
Published: November 2022

Background

While clinical decision rules have been developed to evaluate exacerbations and decisions on hospitalisation and discharge in emergency departments (EDs) in patients with chronic obstructive pulmonary disease (COPD), these rules are not widely used in EDs. In this study, we compare the predictive efficacy of the Ottawa Chronic Obstructive Pulmonary Disease Risk Scale (OCRS) and the Dyspnea, Eosinopenia, Consolidation, Acidemia, and Atrial Fibrillation (DECAF) score in estimating the short-term poor outcome of patients in our ED with exacerbations of COPD.

Methods

This single-centre prospective observational study was conducted over 6 months. Patients with acute exacerbations of COPD admitted to the ED during the study period were included in the study. A poor outcome was defined as any of the following: readmission and requiring hospitalisation within 14 days of discharge, requiring mechanical ventilation on the first admission, hospitalisation for longer than 14 days on the first admission, or death within 30 days. The sensitivity and specificity of the OCRS and the DECAF score for a poor outcome and for mortality were calculated.

Results

Of the 385 patients who participated in the study, 85 were excluded based on the exclusion criteria. 66% of the patients were male, and the mean age was 70.15±10.36 years. A total of 20.7% of all patients (n=62) experienced poor outcomes. The sensitivity of an OCRS score <1 for predicting a poor outcome in patients was 96.8% (95% CI 88.8–99.6%) and the specificity was 18.5% (95% CI 13.8–24.0%). The sensitivity and specificity of an OCRS score <2 were 83.3% (95% CI 35.9–99.6%) and 65.5% (95% CI 59.6–70.7%), respectively. The sensitivity and specificity of a DECAF score <1 were 88.7% (95% CI 78.1–95.3%) and 34.5% (95% CI 28.4–40.9%), respectively. When the DECAF score was <2, sensitivity and specificity were 69.3% (95% CI 56.4–80.4%) and 74.8% (95% CI 68.8–80.2%), respectively.

Conclusion

Our physicians achieved high specificity but low sensitivity in predicting a poor outcome. The OCRS is the more sensitive of the two tools, while the DECAF score is more specific in predicting a poor outcome when all threshold values are evaluated. While both tools may results in unnecessary hospitalisation, they can reduce the incidence of hospital discharge of patients with exacerbations of COPD who will develop poor outcomes in the ED.
Screening of sperm antigen epitopes by phage display technique and its preliminary clinical application
Authors: Lu Jin-Chun , Ge Yan-Mei , Xu Yuan-Hua , Tang Shan-Shan , Liang Yuan-Jiao
Published: November 2022

Background

At present, there is a lack of standardized preparation methods of sperm antigen for the detection of antisperm antibody (AsAb). To screen sperm antigen mimotopes from a phage display random peptide library and use them to establish an enzyme-linked immunosorbent assay (ELISA) for the detection of AsAb, immunoglobulins were extracted from the sera of rabbits with positive AsAb and negative AsAb, respectively, by the saturated ammonium sulfate method, and a phage display 12-mer peptide library was affinity panned by the extracted immunoglobins coated on the ELISA plate. Then, the obtained positive phage clones were identified by ELISA and sent for sequencing and peptides synthesis. Last, a diagnostic ELISA was established to detect clinical serum and seminal plasma samples.

Results

A total of sixty phage clones were chosen by affinity panning, and sixteen of them reacted positively with AsAb in indirect ELISA and sandwich ELISA. Following DNA sequencing and translation, the peptide sequences of the sixteen positive clones were obtained. By comparison in Blast database, four of sixteen positive clones were found to be closely related to male reproduction. Two (#1 and #25) of four mimotopes were synthesized, and an ELISA method was established using the two mimotopes as sperm specific antigens. One hundred and thirty-four serum samples and seventy-four seminal plasma samples from infertile couples were analyzed by the established ELISA with #1 and #25 mimotopes, respectively. The positive rates of AsAb in serum samples were 20.15% (27/134) for #1 and 11.19% (15/134) for #25, respectively, and the coincidence rate between them was 91.04% (122/134). The positive rates of AsAb in seminal plasma samples were 1.35% (1/74) for both #1 and #25, and the coincidence rate was 100%.

Conclusion

Sperm antigen mimotopes can be obtained successfully by the phage display technique, and can be used as standard sperm specific antigens to establish an ELISA method for the detection of AsAb.
Associations of patient-generated subjective global assessment (PG-SGA) and NUTRISCORE with survival in gastric cancer patients: timing matters, a retrospective cohort study
Authors: Cho Jae Won , Youn Jiyoung , Kim Eun Mee , Choi Min-Gew , Lee Jung Eun
Published: November 2022

Background

The timing of nutritional assessment may be important to treat cancer patients and predict their prognosis. This study examined whether Patient-Generated Subjective Global Assessment (PG-SGA) and NUTRISCORE scores were associated with survival among gastric cancer patients who underwent surgery and chemotherapy and whether the timing of the assessment after surgery mattered.

Methods

A total of 952 gastric cancer patients (622 men and 330 women) were included in this retrospective cohort study. The PG-SGA and NUTRISCORE scores were calculated at 1 month (n = 952), 2 months (n = 657), and 3 months (n = 294) after surgery. Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

The PG-SGA scores assessed at 1 month after gastrectomy were not associated with survival. However, high PG-SGA scores at 2 months after gastrectomy (median = 65 days) were associated with an increased risk of mortality; the HR (95% CI) was 2.26 (1.22–4.21) for 9–11 vs. ≤ 5 of PG-SGA scores. When we included patients who received all three consecutive consultations, HR (95% CI) was 2.56 (1.02–6.42) for ≥ 9 (malnutrition) vs. ≤ 8 of PG-SGA scores assessed at 3 months after surgery (median days = 98 days). Likewise, high NUTRISCORE scores assessed at the 3-month follow-up were associated with higher mortality; the HR (95% CI) was 3.84 (1.18–12.55) for ≥ 7 vs. ≤ 4 of NUTRISCORE scores.

Conclusion

Malnutrition assessed with the PG-SGA and NUTRISCORE at 2 to 3 months after gastrectomy was associated with poor survival among gastric cancer patients. Our findings suggest that the timing of the nutritional evaluation may be important in identifying and treating malnutrition related to gastric cancer prognosis.
Pharmacodynamic mechanisms behind a refractory state in inflammatory bowel disease
Authors: Goll Rasmus , Moe Øystein K. , Johnsen Kay-Martin , Meyer Renate , Friestad Joachim , Gundersen Mona D. , Kileng Hege , Johnsen Knut , Florholmen Jon R.
Published: November 2022

Background and aims

Biological therapy for inflammatory bowel disease is efficient in many cases but not all. The underlying molecular mechanisms behind non-response to biological therapy in inflammatory bowel disease are poorly described. Therefore, we aimed to characterize the mucosal cytokine transcript profile in non-immunogenic, non-responder patients with adequate trough level.

Material and methods

Patients with ulcerative colitis (UC) (n = 21) and Crohn’s disease (CD) (n = 12) with non-response to biological therapy (anti-tumor necrosis factor (TNF) or vedolizumab) were included. Reference groups were A: untreated patients with UC or CD at debut of disease who had severe 1-year outcome, B: patients with UC or CD treated to endoscopic remission with biological agents, and C: healthy normal controls. Mucosal transcripts of TNF, interleukin (IL)17 and IL23 were measured by reverse transcription real-time quantitative polymerase chain reaction.
Results
Of the non-responders, 2 out of 12 CD and 1 out of 21 UC patients needed surgery during follow-up. Of the remaining non-responding patients, 8 out of 10 CD and 12 out of 20 UC patients switched biologic treatment. The remaining 2 CD and 8 UC patients continued treatment with the same biological agent with the addition of steroids, immunomodulators (AZA/MTX) and /or local steroids/5ASA. Twelve (8 UC/4 CD) out of 20 IBD patients were still non-responders after changing biological therapy to either anti-TNF (2), vedolizumab (9) or ustekinumab (1).

The transcripts of IL17, IL23 and TNF were significantly upregulated in the non-response group compared to normal controls and patients in remission. In UC, 24% of the non-responders had normal mucosal TNF transcript indicating a non-TNF mediated inflammation. No obvious differences in gene expression were observed between primary and secondary non-responders, nor between anti-TNF and vedolizumab non-responders.

Conclusions

Mucosal transcripts of IL17 and IL23 are highly associated with non-response to biological therapy, whereas some UC patients may also have a non-TNF mediated inflammatory pathway.
The factors that influence care home residents’ and families’ engagement with decision-making about their care and support: an integrative review of the literature
Authors: Lynch Brighide , Ryan Assumpta A. , O’Neill Marie , Penney Sarah
Published: November 2022

Background:

As care homes play an important role in the lives of an increasing number of older people, it is pivotal to understand how residents’ and their families engage in decision-making about their care and support. Internationally, there is an increasing emphasis in long-term care settings on the right of residents to be actively involved in all aspects of decision-making about their care and support. However, the steps necessary to achieving a culture of shared decision-making in long-term care settings remain unclear. The aim of this literature review is to summarise what is known in the literature about the factors that influence care home residents’ and families’ engagement with decision-making about their care and support.

Methods:

An integrative literature reviews was carried out, guided by the methodological framework proposed by Whittemore and Knafl (2005). CINAHL, Medline Ovid and ProQuest Health and Medical databases were searched for relevant articles from 2011 to 2021. A three-step method was used, including the use of reference and citation management software to manage search results and identify duplicate citations. Abstracts and full texts were reviewed by two reviewers. Details of the selected articles were then extracted using the Data Extraction Form.

Results:

In total, 913 articles were located and 22 studies were included in the final analysis. The thematic analysis identified three main themes that illustrate the complexities of shared decision-making in care homes: (a) a positive culture of collaborative and reciprocal relationships; (b) a willingness to engage and a willingness to become engaged; and (c) communicating with intent to share and support rather than inform and direct.

Conclusion:

The implementation of shared decision-making in care homes is highly dependent on the support and nurturing of collaborative and reciprocal relationships between residents, families, and staff. Part of this process includes ascertaining the willingness of residents and families to become engaged in shared decision-making. Communication skills training for staff and guided approaches that view decision-making as a supportive process rather than a once off event are essential prerequisites for implementation.
Quantifying differences in packaged food and drink purchases among households with diet-related cardiometabolic multi-morbidity: a cross-sectional analysis
Authors: Ricket Iben M. , Brown Jeremiah R. , MacKenzie Todd A. , Ma Yu , Grewal Dhruv , Ailawadi Kusum L. , Emond Jennifer A.
Published: November 2022

Background

Diet is important for chronic disease management, with limited research understanding dietary choices among those with multi-morbidity, the state of having 2 or more chronic conditions.

The objective of this study was to identify associations between packaged food and drink purchases and diet-related cardiometabolic multi-morbidity (DRCMM).

Methods

Cross-sectional associations between packaged food and drink purchases and household DRCMM were investigated using a national sample of U.S. households participating in a research marketing study. DRCMM households were defined as household head(s) self-reporting 2 or more diet-related chronic conditions. Separate multivariable logistic regression models were used to model the associations between household DRCMM status and total servings of, and total calories and nutrients from, packaged food and drinks purchased per month, as well as the nutrient density (protein, carbohydrates, and fat per serving) of packaged food and drinks purchased per month, adjusted for household size.

Results

Among eligible households, 3795 (16.8%) had DRCMM. On average, households with DRCMM versus without purchased 14.8 more servings per capita, per month, from packaged foods and drinks (p < 0.001). DRCMM households were 1.01 times more likely to purchase fat and carbohydrates in lieu of protein across all packaged food and drinks (p = 0.002,p = 0.000, respectively). DRCMM households averaged fewer grams per serving of protein, carbohydrates, and fat per month across all food and drink purchases (allp < 0.001). When carbonated soft drinks and juices were excluded, the same associations for grams of protein and carbohydrates per serving per month were seen (bothp < 0.001) but the association for grams of fat per serving per month attenuated.

Conclusions

DRCMM households purchased greater quantities of packaged food and drinks per capita than non-DRCMM households, which contributed to more fat, carbohydrates, and sodium in the home. However, food and drinks in DRCMM homes on average were lower in nutrient-density. Future studies are needed to understand the motivations for packaged food and drink choices among households with DRCMM to inform interventions targeting the home food environment.
Bronchial artery diameter in massive hemoptysis in cystic fibrosis
Authors: Dohna Martha , Kühl Hilmar , Sutharsan Sivagurunathan , Dohna-Schwake Christian , Vo Chieu Van Dai , Hellms Susanne , Kornemann Norman , Renz Diane M. , Montag Michael J.
Published: November 2022

Background

Massive hemoptysis is a rare but potentially life-threatening condition of patients with cystic fibrosis (CF) and advanced pulmonary disease. Hypertrophied bronchial arteries are understood to cause massive hemoptysis when rupturing. Risk factors to predict massive hemoptysis are scarce and bronchial artery diameters are not part of any scoring system in follow-up of patients with CF. Aim of this study was to correlate bronchial artery diameter with massive hemoptysis in CF.

Methods

Bronchial artery and non-bronchial systemic artery diameters were measured in contrast enhanced computed tomography (CT) scans in patients with massive hemoptysis and compared to patients with end-stage CF and no history of hemoptysis. Demographic and clinical data and side of bronchial artery/non-bronchial systemic artery hypertrophy and coil embolization were documented.

Results

In this retrospective multicenter study 33 patients with massive hemoptysis were included for bronchial artery/non-bronchial systemic artery diameter measurements, (13 female, 20 male, median age 30 years (18–55)). Bronchial artery diameters were significantly larger in the case group than in the control group with median 4 mm (2.2–8.2 mm), and median 3 mm (1–7 mm), respectively (p = 0.002). Sensitivity of bronchial arteries ≥ 3.5 mm to be associated with hemoptysis was 0.76 and specificity 0.71 with ROC creating an area under the curve of 0.719. If non-bronchial systemic arteries were present, they were considered culprit and embolized in 92% of cases.

Conclusion

Bronchial arteries ≥ 3.5 mm and presence of hypertrophied non-bronchial systemic arteries correlate with massive hemoptysis in patients with CF and might serve as risk predictor for massive hemoptysis. Therefore, in patients with advanced CF we propose CT scans to be carried out as CT angiography to search for bronchial arteries ≥ 3.5 mm and for hypertrophied non-bronchial systemic arteries as possible risk factors for massive hemoptysis.
Assessment of soft and hard tissue characteristics of ridge preservation at molar extraction sites with severe periodontitis: a randomized controlled trial
Authors: Zhang Haoyun , Wei Yiping , Xu Tao , Zhen Min , Wang Cui , Han Ziyao , Hu Wenjie , Chung Kwok-Hung
Published: November 2022

Background

Changes in alveolar bone dimension after tooth extraction may affect placement of the subsequent implant, resulting in ridge deficiency that can adversely impact long-term implant stability or aesthetics. Alveolar ridge preservation (ARP) was effective in reducing the amount of ridge resorption following tooth extraction. There is sparse evidence regarding the benefit of ARP at periodontally compromised molar extraction sockets. This study will be a randomized trial to assess the soft tissue contour, radiographical, and histological changes of ARP at molar extraction sites in order to compare severe periodontitis cases with natural healing results and determine the most beneficial and least traumatic clinical treatment for such patients.

Methods

This research is designed as a two-group parallel randomized controlled trial. The total number of tooth extraction sites will be 70 after calculation with power analysis. Teeth will be randomly assigned to two groups with the test group conducting ridge preservation and the control group healing naturally. Periodontal examination, cone beam-computed tomography (CBCT) data, and stereolithographic (STL) files obtained by intraoral scanning will be collected through the follow-up period, and bone biopsy samples would be obtained during implant surgery. The primary outcomes are the vertical and horizontal change of alveolar ridge measured on CBCT images, soft tissue contour changes evaluated by superimposing the digital impressions, alterations of mucosa thickness (as measured by superimposing the CBCT data and STL files), histological features of implant sites and periodontal parameter changes. The secondary outcomes are patient-reported post-operative reaction and conditions of simultaneous bone graft or sinus lifting procedures during implantation.

Discussion

This study will provide information about hard and soft tissue dimension changes and histomorphology evaluation following ARP and natural healing in periodontally compromised molar sites, which may contribute to complement the missing information of ARP at periodontally compromised molar extraction sockets.

Trial registration

Chinese Clinical Trial Register (ChiCTR) ChiCTR2200056335. Registered on February 4, 2022, Version 1.0.
A randomized controlled trial of a multi-modal palliative care intervention to promote advance care planning and psychological well-being among adults with advanced cancer: study protocol
Authors: Arch Joanna J. , Mitchell Jill L. , Schmiege Sarah J. , Levin Michael E. , Genung Sarah R. , Nealis Madeline S. , Fink Regina M. , Bright Emma E. , Andorsky David J. , Kutner Jean S.
Published: November 2022

Background

Up to half of adults with advanced cancer report anxiety or depression symptoms, which can cause avoidance of future planning. We present a study protocol for an innovative, remotely-delivered, acceptance-based, multi-modal palliative care intervention that addresses advance care planning (ACP) and unmet psychological needs commonly experienced by adults with metastatic cancer.

Methods

A two-armed, prospective randomized controlled trial (RCT) randomizes 240 adults with Stage IV (and select Stage III) solid tumor cancer who report moderate to high anxiety or depression symptoms to either the multi-modal intervention or usual care. The intervention comprises five weekly two-hour group sessions (plus a booster session one month later) delivered via video conferencing, with online self-paced modules and check-ins completed between the group sessions. Intervention content is based on Acceptance and Commitment Therapy (ACT), an acceptance, mindfulness, and values-based model. Participants are recruited from a network of community cancer care clinics, with group sessions led by the network’s oncology clinical social workers. Participants are assessed at baseline, mid-intervention, post-intervention, and 2-month follow-up. The primary outcome is ACP completion; secondary outcomes include anxiety and depression symptoms, fear of dying, and sense of life meaning. Relationships between anxiety/depression symptoms and ACP will be evaluated cross-sectionally and longitudinally and theory-based putative mediators will be examined.

Discussion

Among adults with advanced cancer in community oncology settings, this RCT will provide evidence regarding the efficacy of the group ACT intervention on ACP and psychosocial outcomes as well as examine the relationship between ACP and anxiety/ depression symptoms. This trial aims to advance palliative care science and inform clinical practice.

Trial Registration

Clinicaltrials.gov NCT04773639 on February 26, 2021.
Self-assessment scale for the community-based and emergency practice
Authors: Wakabayashi Takao , Tsuji Yoshihisa , Yamamoto Takeshi , Sohma Hitoshi , Yamamoto Wari
Published: November 2022

Background

For current medical education, community-based primary care for the elderly is an essential topic. This study aimed to establish a scale of community-based assessment for clinical and emergency practice (C-CEP).

Methods

A self-assessment scale for C-CEP was developed according to four steps. Initially, we reviewed publications from the societies of the United States, British, and Japan regarding educational goals. In addition, we searched MEDLINE for educational goals regarding attitude, skills, and knowledge. Getting together, we established 23 items as the educational goals of the C-CEP. Second, we collected responses for these 23 items from 5th-grade medical students (n = 195). Third, we conducted an exploratory factor analysis (EFA) using their responses to determine the fundamental structure of the self-assessment scale. Finally, a confirmatory factor analysis (CFA) was performed to assess the fitness of the self-assessment scale developing the EFA, resulting in modification of the items.

Results

In EFA and CFA results, C-CEP Scale consisted of four factors with 15 items: “Attitude and communication in emergency care,” Basic clinical skills,” “Knowledge of community healthcare,“ and “Knowledge of evidence-based medicine perseverance.” The model fit indices were acceptable (Goodness of Fix Index = 0.928, Adjusted Goodness of Fit Index = 0.900, Comparative Fit Index = 0.979, and Root Mean Square Error of Approximation = 0.045). The values of McDonald’s omega as an estimate of scale reliability were more than 0.7 in all four factors. As for test-retest reliability, the intraclass correlation coefficients were ≥ 0.58 for all factors. All four factors of the C-CEP Scale correlated positively with the Medical Professionalism Evaluation Scale subscales.

Conclusions

We developed a valid and reliable self-assessment scale to assess student competence.
Ethical preparedness in health research and care: the role of behavioural approaches
Authors: Samuel G. , Ballard L. M. , Carley H. , Lucassen A. M.
Published: November 2022

Background

Public health scholars have long called for preparedness to help better negotiate ethical issues that emerge during public health emergencies. In this paper we argue that the concept of ethical preparedness has much to offer other areas of health beyond pandemic emergencies, particularly in areas where rapid technological developments have the potential to transform aspects of health research and care, as well as the relationship between them. We do this by viewing the ethical decision-making process as a behaviour, and conceptualising ethical preparedness as providing a health research/care setting that can facilitate the promotion of this behaviour. We draw on an implementation science and behaviour change model, COM-B, to demonstrate that to be ethically prepared requires having the capability (ability), opportunity, and motivation (willingness) to work in an ethically prepared way.

Methods

We use two case examples from our empirical research—one pandemic and one non-pandemic related—to illustrate how our conceptualisation of ethical preparedness can be applied in practice. The first case study was of the UK NHSX COVID-19 contact tracing application case study involved eight in-depth interviews with people involved with the development/governance of this application. The second case involved a complex case regarding familial communication discussed at the UK Genethics Forum. We used deductive qualitative analysis based on the COM-B model categories to analyse the transcripbed data from each case study.

Results

Our analysis highlighted that being ethically prepared needs to go beyond merely equipping health professionals with skills and knowledge, or providing research governance actors with ethical principles and/or frameworks. To allow or support these different actors to utilise their skills and knowledge (or principles and frameworks), a focus on the physical and social opportunity is important, as is a better understanding the role of motivation.

Conclusions

To understand ethical preparedness, we need to view the process of ethical decision-making as a behaviour. We have provided insight into the specific factors that are needed to promote this behaviour—using examples from both in the pandemic context as well as in areas of health research and medicine where there have been rapid technological developments. This offers a useful starting point for further conceptual work around the notion of being ethically prepared.
Detection of K-complexes in EEG waveform images using faster R-CNN and deep transfer learning
Authors: Khasawneh Natheer , Fraiwan Mohammad , Fraiwan Luay
Published: November 2022

Background

The electroencephalography (EEG) signal carries important information about the electrical activity of the brain, which may reveal many pathologies. This information is carried in certain waveforms and events, one of which is the K-complex. It is used by neurologists to diagnose neurophysiologic and cognitive disorders as well as sleep studies.
Existing detection methods largely depend on tedious, time-consuming, and error-prone manual inspection of the EEG waveform.

Methods

In this paper, a highly accurate K-complex detection system is developed. Based on multiple convolutional neural network (CNN) feature extraction backbones and EEG waveform images, a regions with faster regions with convolutional neural networks (Faster R-CNN) detector was designed, trained, and tested. Extensive performance evaluation was performed using four deep transfer learning feature extraction models (AlexNet, ResNet-101, VGG19 and Inceptionv3). The dataset was comprised of 10948 images of EEG waveforms, with the location of the K-complexes included as separate text files containing the bounding boxes information.

Results

The Inceptionv3 and VGG19-based detectors performed consistently high (i.e., up to 99.8% precision and 0.2% miss rate) over different testing scenarios, in which the number of training images was varied from 60% to 80% and the positive overlap threshold was increased from 60% to 90%.

Conclusions

Our automated method appears to be a highly accurate automatic K-complex detection in real-time that can aid practitioners in speedy EEG inspection.

Graphical Abstract
Cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar compared with lenvatinib as the first-line treatment of unresectable or metastatic hepatocellular carcinoma
Authors: Zhou Ting , Wang Xintian , Cao Yingdan , Yang Lan , Wang Zijing , Ma Aixia , Li Hongchao
Published: November 2022

Background

In recent years, programmed cell death protein-1 inhibitors, including sintilimab, have significantly prolonged the overall survival time of patients with unresectable or metastatic hepatocellular carcinoma (HCC); however, the cost-effectiveness of sintilimab is unclear. The aim of this study was to assess the cost-effectiveness of sintilimab plus bevacizumab biosimilar compared with lenvatinib as first-line treatment in patients with unresectable or metastatic HCC.

Methods

A lifetime partitioned survival model was developed to conduct a cost-effectiveness analysis of sintilimab plus bevacizumab biosimilar vs. lenvatinib for advanced HCC from a Chinese healthcare system perspective. The clinical and safety data were derived from two recent randomized clinical trials, the ORIENT-32 and REFLECT studies. Utility data were obtained from previous studies. Long-term direct medical costs and quality-adjusted life-years (QALYs) were predicted. Deterministic and probabilistic sensitivity analyses were performed to verify the robustness of the model.

Results

Compared with lenvatinib, combination therapy with sintilimab and bevacizumab biosimilar yielded an additional 0.493 QALYs at a higher cost ($33,102 vs. $21,037) (2021 US dollars). This resulted in a deterministic incremental cost-effectiveness ratio (ICER) of $24,462 per QALY in the base-case analysis. The ICERs were sensitive to the utility of post-progression and the cost of bevacizumab biosimilar. A lower ICER was estimated when the dose of bevacizumab biosimilar decreased from 15 mg to 7.5 mg per kilogram in the scenario analysis. In the probabilistic sensitivity analysis, the probability of being cost-effective for sintilimab treatment at willingness-to-pay (WTP) thresholds of one ($12,516) and three times the gross domestic product per capita in China ($37,547) were 11.6% and 88.6%, respectively.

Conclusion

Sintilimab plus bevacizumab biosimilar is likely to be a cost-effective treatment option as a first-line treatment for unresectable or metastatic HCC in China when WTP threshold is over $23,650.
Impact of mental disorders on the risk of atrial fibrillation in patients with diabetes mellitus: a nationwide population-based study
Authors: Bae Nan Young , Lee So-Ryoung , Choi Eue-Keun , Ahn Hyun Jin , Ahn Hyo-Jeong , Kwon Soonil , Han Kyung-Do , Lee Kyu-Na , Oh Seil , Lip Gregory Y. H.
Published: November 2022

Background

It is unclear whether mental disorders are an independent risk factor for atrial fibrillation (AF) in patients with diabetes. We aimed to investigate whether patients with diabetes who have mental disorders have an increased risk for AF.

Methods

Using the Korea National Health Insurance Service database, we enrolled 2,512,690 patients diagnosed with diabetes without AF between 2009 and 2012. We assessed five mental disorders: depression, insomnia, anxiety, bipolar disorder, and schizophrenia. Newly diagnosed AF was identified during the follow-up period, and multivariate Cox regression analysis was performed.

Results

Among the 2,512,690 patients (mean age 57.2 ± 12.3 years; 60.1% men), 828,929 (33.0%) had mental disorders. Among the five mental disorders, anxiety (68.1%) was the most common, followed by insomnia (40.0%). During a median follow-up duration of 7.1 years, new-onset AF was diagnosed in 79,525 patients (4.66 per 1,000 person-years). Patients with diabetes who had mental disorders showed a higher risk for AF (adjusted hazard ratio [HR] 1.19; 95% confidence interval [CI] 1.17–1.21; p-value < 0.001). Depression, insomnia, and anxiety were significantly associated with higher risk for AF (adjusted HR [95% CI]: 1.15 [1.12–1.17], 1.15 [1.13–1.18], and 1.19 [1.67–1.21], respectively; all p-values < 0.001), whereas bipolar disorder and schizophrenia were not.

Conclusions

Mental disorders, especially depression, insomnia, and anxiety, were associated with an increased risk for AF in patients with diabetes. Greater awareness with a prompt diagnosis of AF should be considered for patients with both DM and mental disorders.
Association of triglyceride-glucose index with ischemic stroke recurrence in nondiabetic patients with small vessel occlusion: a multicenter hospital-based prospective cohort study
Authors: Wu Li , Zhu Jinmao , Li Chenghao , Zhu Juehua , Dai Zheng , Jiang Yongjun
Published: November 2022

Background

Triglyceride-glucose (TyG) index is a simple and reliable surrogate marker of insulin resistance. Elevated TyG index was related to stroke recurrence. This study aimed to explore the associations between TyG index with ischemic stroke recurrence in nondiabetic patients with small vessel occlusion.

Methods

From November 1, 2016 to February 28, 2021, consecutive acute ischemic stroke patients admitted within 1 week after onset were screened. The stroke mechanism was determined based on medical history, laboratory examinations, cardiac examinations, vascular examinations and neuroimaging. Nondiabetic patients with small vessel occlusion were enrolled and followed up for 1 year. The primary outcome was ischemic stroke recurrence. Logistic regression and Kaplan–Meier survival curve were used to analyze the association of the TyG index and stroke recurrence.

Results

A total of 6100 acute ischemic stroke patients were screened, with 1970 nondiabetic patients with small vessel occlusion included and divided into 4 groups according to the TyG index quartiles (Q1: < 8.20; Q2: 8.20–8.53; Q3: 8.54–8.92; Q4: > 8.92). There were significant differences in age, body mass index, systolic blood pression, diastolic blood pressure, lipid-lowering agents, infarct location, fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, uric acid, and stroke recurrence among the 4 groups. In the multi-adjusted models, compared to Q1 of the TyG index, the odds ratio for Q4 of the TyG index for stroke recurrence was 3.100 (1.366–8.019). The Kaplan–Meier survival (ischemic stroke-free) curves by quartiles of the TyG index also showed statistically significant differences (log-rank test, P = 0.004).

Conclusions

Our findings suggested that the TyG index was associated with ischemic stroke recurrence in nondiabetic patients with small vessel occlusion, and it could be a valuable biomarker for assessing the risk of ischemic stroke recurrence in these patients.
Status of the health information system in Ireland and its fitness to support health system performance assessment: a multimethod assessment based on stakeholder involvement
Authors: Ivanković Damir , Jansen Tessa , Barbazza Erica , Fernandes Óscar Brito , Klazinga Niek , Kringos Dionne
Published: November 2022

Background

Between 2019 and 2021, the first Irish health system performance assessment (HSPA) framework was developed. As routinely collected health data are necessary to continuously populate indicators of an HSPA framework, a purpose-driven assessment of the health information system (HIS) in Ireland and its fitness to support the implementation of an HSPA framework was conducted. This study reports on the status of the Irish HIS through a multimethod assessment based on continuous broad stakeholder involvement.

Methods

Between May and November 2020, over 50 informants were engaged in individual and group interviews and stakeholder consultation workshops as part of the HIS assessment process. Descriptive themes and high-level data availability heatmaps were derived from interview and workshop data using thematic analysis. Indicator “passports” for the HSPA framework were populated during stakeholder consultation workshops and analysed using univariate descriptive statistics.

Results

The HIS in Ireland was able to provide administrative, survey and registry-based data for public sector acute care services, focusing on structure, process and output metrics. Significant data availability gaps, most notably from primary care, private hospitals and community care, were reported, with little availability of electronic health record and people-reported data. Data on outcome metrics were mostly missing, as were linkage possibilities across datasets for care pathway monitoring. The COVID-19 pandemic highlighted the national HIS’s shortcomings but also the capacity for rapid development and improvement.

Conclusions

A tailor-made assessment of the HIS in Ireland, involving a broad set of relevant stakeholders, revealed strengths, weaknesses and areas for improvement in the Irish health data landscape. It also contributed to the development of a national HSPA framework and momentum to further strengthen data infrastructure and governance, while working towards a more data-driven and person-centred healthcare system. This work demonstrates the utility of an inclusive HIS assessment process and is applicable beyond Ireland, where this case study was conducted.
Diagnostic delay in rare diseases: data from the Spanish rare diseases patient registry
Authors: Benito-Lozano Juan , López-Villalba Blanca , Arias-Merino Greta , Posada de la Paz Manuel , Alonso-Ferreira Verónica
Published: November 2022

Background

According to the International Rare Diseases Research Consortium (IRDiRC), a known rare disease (RD) should be diagnosable within a year. This study sought: firstly, to ascertain how long it takes to obtain the diagnosis of a RD in Spain, along with its associated time trend; and secondly, to identify and measure diagnostic delay (defined by the IRDiRC as any period exceeding a year) by reference to the characteristics of RDs and the persons affected by them.

Methods

Using data sourced from the Spanish Rare Diseases Patient Registry, we performed a descriptive analysis of the time elapsed between symptom onset and diagnosis of each RD, by sex, age and date of symptom onset, and type of RD. We analysed the time trend across the period 1960–2021 and possible change points, using a Joinpoint regression model and assuming a Poisson distribution. The multivariate analysis was completed with backward stepwise logistic regression.

Results

Detailed information was obtained on 3304 persons with RDs: 56.4% had experienced delay in diagnosis of their RDs, with the mean time taken being 6.18 years (median = 2; IQR 0.2–7.5). Both the percentage of patients with diagnostic delay and the average time to diagnosis underwent a significant reduction across the study period (p < 0.001). There was a higher percentage of diagnostic delays: in women (OR 1.25; 95% CI 1.07–1.45); in cases with symptom onset at age 30–44 years (OR 1.48; 95% CI 1.19–1.84): and when analysed by type of RD, in mental and behavioural disorders (OR 4.21; 95% CI 2.26–7.85), followed by RDs of the nervous system (OR 1.39; 95% CI 1.02–1.88).

Conclusions

This is the first study to quantify time to diagnosis of RDs in Spain, based on data from a national registry open to any RD. Since over half of all persons affected by RDs experience delay in diagnosis, new studies are needed to ascertain the factors associated with this delay and the implications this has on the lives of patients and their families.
TREM2 and microglia exosomes: a potential highway for pathological tau
Authors: Jain Nimansha , Ulrich Jason D.
Published: November 2022

Tau pathology appears to spread along neuronal networks via the template misfolding of tau by pathological tau conformations. The mechanisms underlying neuron-to-neuron transmission of tau are unclear and recent work demonstrates a role for microglia in the spread of tau pathology. In this Commentary, we discuss a recent study that found that loss of TREM2 expression resulted in exacerbated spread of tau pathology that depended on microglial exosomes. These important findings highlight the role of the microglial endolysosomal system and TREM2 in the spread of tau pathology.
Protocol for the development of an international Core Outcome Set for treatment trials in adults with epilepsy: the EPilepsy outcome Set for Effectiveness Trials Project (EPSET)
Authors: Mitchell James W. , Noble Adam , Baker Gus , Batchelor Rachel , Brigo Francesco , Christensen Jakob , French Jacqueline , Gil-Nagel Antonio , Guekht Alla , Jette Nathalie , Kälviäinen Reetta , Leach John Paul , Maguire Melissa , O’Brien Terence , Rosenow Felix , Ryvlin Philippe , Tittensor Phil , Tripathi Manjari , Trinka Eugen , Wiebe Samuel , Williamson Paula R. , Marson Tony
Published: November 2022

Background

A Core Outcome Set (COS) is a standardised list of outcomes that should be reported as a minimum in all clinical trials. In epilepsy, the choice of outcomes varies widely among existing studies, particularly in clinical trials. This diminishes opportunities for informed decision-making, contributes to research waste and is a barrier to integrating findings in systematic reviews and meta-analyses. Furthermore, the outcomes currently being measured may not reflect what is important to people with epilepsy.

Therefore, we aim to develop a COS specific to clinical effectiveness research for adults with epilepsy using Delphi consensus methodology.

Methods

The EPSET Study will comprise of three phases and follow the core methodological principles as outlined by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. Phase 1 will include two focused literature reviews to identify candidate outcomes from the qualitative literature and current outcome measurement practice in phase III and phase IV clinical trials. Phase 2 aims to achieve international consensus to define which outcomes should be measured as a minimum in future trials, using a Delphi process including an online consensus meeting involving key stakeholders. Phase 3 will involve dissemination of the ratified COS to facilitate uptake in future trials and the planning of further research to identify the most appropriate measurement instruments to use to capture the COS in research practice.

Discussion

Harmonising outcome measurement across future clinical trials should ensure that the outcomes measured are relevant to patients and health services, and allow for more meaningful results to be obtained.

Core Outcome Set registration

COMET Initiative as study 118.
EC-18 prevents autoimmune arthritis by suppressing inflammatory cytokines and osteoclastogenesis
Authors: Park Jin-Sil , Yang Seung Cheon , Jeong Ha Yeon , Lee Seon-Young , Ryu Jun-Geol , Choi Jeong Won , Kang Hye Yeon , Kim Sung-Min , Hwang Sun-Hee , Cho Mi-La , Park Sung-Hwan
Published: November 2022

Background

EC-18, a synthetic monoacetyldiaglyceride, exhibits protective effects against lung inflammation, allergic asthma, and abdominal sepsis. However, there have been no investigations to determine whether EC-18 has preventive potential in autoimmune diseases, especially rheumatoid arthritis (RA).

Methods

To investigate the efficacy of EC-18 on the development of RA, EC-18 was administered in a collagen-induced arthritis (CIA) murine model and disease severity and the level of inflammatory cytokines in the joint were investigated. The effect of EC-18 on the inflammation-related factors was investigated by flow cytometry, ELISA, western blot, and real-time PCR in splenocytes from mice and in peripheral blood mononuclear cells from healthy and patients with RA. The effect of EC-18 on osteoclastogenesis was investigated.

Results

EC-18 effectively reduced the clinical and histological severity of arthritis, similar to Janus kinase inhibitors include tofacitinib and baricitinib, in CIA. Furthermore, EC-18 exhibited a synergistic effect with methotrexate in preventing CIA. Treatment with EC-18 effectively reduced the production of inflammatory cytokines in immune cells and osteoclast differentiation in mice and patients with RA.

Conclusion

These results suggest that EC-18 may be an effective strategy for RA.
Acute circulatory and femoral hemodynamic responses induced by standing core exercise at different rotational cadence: a crossover study
Authors: Lin Hsin-Fu , Chou Chun-Chung , Chao Hsiao-Han , Wang Soun-Cheng , Chen Chen-Huan
Published: November 2022

Background

Core exercise is often adopted as an adjunct in maintaining musculoskeletal health in rehabilitation; we previously showed that standing core rotational exercise improves femoral blood flow after training. This study aimed to investigate the effects of different rotational cadences on circulatory and hemodynamic responses after acute standing core exercise.

Methods

Sixteen healthy male adults (22 ± 1 yrs) were randomly assigned to participate in two 30-min standing core exercises of fast (75 rpm, FC) and slow cadence (20 rpm, SC) sessions after completing an acute bout of seated knee extension exercise session (KE) (80% of 1 repetition maximum × 12 repetitions × 3 sets). Impedance cardiography-derived circulatory responses and femoral hemodynamics by ultrasound imaging were measured pre- and 30, and 60 min post-exercise.

Results

KE acutely increased post-exercise cardiac output at 30 min (p = 0.008) and heart rate at 30 min (p = 0.04) and 60 min (p = 0.01), yet brachial blood pressure did not change. Systemic vascular resistance was significantly lower after FC and KE at 30 min (p = 0.008) and 60 (p = 0.04) min, respectively, compared with the baseline. In addition, KE acutely decreased post-exercise arterial stiffness (p = 0.05) at 30 min, increased femoral conductance (p = 0.03, p < 0.001), and blood flow (p = 0.009, p < 0.001) at 30 and 60 min. No significant changes were observed in absolute femoral blood flow after FC and SC, except that FC significantly increased relative femoral blood flow (p = 0.007) and conductance (p = 0.005). Post-exercise femoral diameter significantly increased in KE at 30 (p = 0.03) and 60 min (p = 0.01), but not in core exercise.

Conclusion

Our results suggest that standing core exercise elicits circulatory and hemodynamic changes only when the rotational cadence is set at a faster cadence, which provides preliminary scientific evidence for its use in exercise programs.
Regulation of alphaherpesvirus protein via post-translational phosphorylation
Authors: Zhou Tong , Wang Mingshu , Cheng Anchun , Yang Qiao , Tian Bin , Wu Ying , Jia Renyong , Chen Shun , Liu Mafeng , Zhao Xin-Xin , Ou Xuming , Mao Sai , Sun Di , Zhang Shaqiu , Zhu Dekang , Huang Juan , Gao Qun , Yu Yanling , Zhang Ling
Published: November 2022

An alphaherpesvirus carries dozens of viral proteins in the envelope, tegument and capsid structure, and each protein plays an indispensable role in virus adsorption, invasion, uncoating and release. After infecting the host, a virus eliminates unfavourable factors via multiple mechanisms to escape or suppress the attack of the host immune system. Post-translational modification of proteins, especially phosphorylation, regulates changes in protein conformation and biological activity through a series of complex mechanisms. Many viruses have evolved mechanisms to leverage host phosphorylation systems to regulate viral protein activity and establish a suitable cellular environment for efficient viral replication and virulence. In this paper, viral protein kinases and the regulation of viral protein function mediated via the phosphorylation of alphaherpesvirus proteins are described. In addition, this paper provides new ideas for further research into the role played by the post-translational modification of viral proteins in the virus life cycle, which will be helpful for understanding the mechanisms of viral infection of a host and may lead to new directions of antiviral treatment.