bluuebunny/crossref_metadata_2025 huggingface dataset:
Get waivered remote: Nationwide, remote DEA-x waiver course in response to COVID-19
Authors: Martin Alister , Raber Joshua P. , Shayer Desiree , Lai Deborah , Goodcoff Adam , Kannikal Jasmine , Raja Ali S. , He Shuhan
Published: October 2021

Problem

As of 2020, less than 5% of physicians in the United States have a drug enforcement administration-X waiver to prescribe buprenorphine. The coronavirus-2019 pandemic restricted in-person gatherings, including traditional drug enforcement administration-X waiver courses. As a result, in-person conferences have needed to adopt remote formats. Many programs identified a gap between educational delivery and the faculty skills required to deliver content remotely.

Approach

To address the need for high-quality remote learning, Get Waivered designed and implemented a novel experience for clinicians, called Get Waivered Remote. An educational session was live-streamed via Zoom™. To foster interactivity, like in-person didactic conferences, participants were polled to facilitate discussion among presenters, learners, and facilitators during the broadcast

Outcomes

The RE-AIM framework was used for evaluation. Our program had a Reach encompassing 814 users that participated during the live-streamed event; Effectiveness with 73.79% reporting being somewhat familiar or very familiar with the practice of opioid dependency treatment with approved buprenorphine medications; Adoption with 95.15% reporting a favorable experience and 92.23% reporting it was similar or more enjoyable than their usual teaching; Implementation with 450 messages sent by 281 users to engage with presenters and other learners via Zoom chat in real time.

Next steps

Get Waivered Remote provides a proof-of-concept that a broadcast with a concurrent, interactive remote learning platform is feasible, low cost, and simple to execute. Further study is required to assess the ability of our group to maintain this innovation and also to measure its impact on the treatment of opioid use disorder.
Social Media Expression and User Predispositions: Applying the Differential Susceptibility to Media Effects Model to the Study of Issue Polarization
Authors: Coles Stewart M. , Saleem Muniba
Published: October 2021

The ability of social media users to express themselves online should be influential for opinion formation, including potential polarization. Still, little is known about how expression interacts with users’ psychological predispositions, especially for controversial topics. The potential for expression to relate to support for social media-based racial justice movements, which could also be affected by underlying feelings of racial resentment, is particularly interesting. We apply the Differential Susceptibility to Media Effects Model (DSMM) to the study of the relationship between social media expression and issue polarization regarding Black Lives Matter. In a survey of social media users conducted during the 2016 U.S. presidential election, we find that racial resentment moderates the relationship between social media expression and support for racial justice movements. Among low-resentment social media users, more frequent expression was associated with less support for Black Lives Matter. In addition, low- versus high-resentment users who expressed themselves on social media more frequently were more polarized in their support for All Lives Matter but less polarized in their support for Black Lives Matter. In line with the DSMM, our findings highlight that users’ psychological predispositions must be taken into account when determining how social media expression relates to issue polarization.
Comparison of Outcomes in Percutaneous Fixation of Traumatic Fractures between Ankylosing Spondylitis and Diffuse Idiopathic Skeletal Hyperostosis
Authors: McCarty Scott , Bruckner Jacob J. , Camacho Jael E. , Jauregui Julio J. , Thomson Alexandra E. , Ye Ivan , Cavanaugh Daniel L. , Koh Eugene Y. , Ludwig Steven C. , Gelb Daniel E.
Published: October 2021

Study Design

Retrospective cohort study.

Objectives

This study aims to analyze outcomes and complications of patients with thoracic and lumbar fractures in the setting of ankylosing spinal disorders (ASD) treated with minimally invasive surgery (MIS).

Methods

The operative logs from 2012 to 2019 from one academic, Level I trauma center were reviewed for cases of thoracic and lumbar spinal fractures in patients with ASD treated with a MIS approach. Variables were compared between patients with ankylosing spondylitis (AS), diffuse idiopathic skeletal hyperostosis (DISH), and advanced spondylosis.

Results

A total of 48 patients with ASD and concomitant thoracic or lumbar spinal fracture managed with an MIS approach were identified. A total of 11 patients were identified with AS, 21 with DISH, and 16 with advanced spondylosis. A total of 27 (56.3%) patients experienced complications. Complications differed between groups; DISH patients experienced a greater number of post-operative complications compared to AS and advanced spondylosis patients ( P = .009). There was no significant difference in length of surgery, estimated blood loss, length of stay, readmission, and reoperation rates between AS and DISH patients. There were 3 mortalities unrelated to the surgery.

Conclusion

Percutaneous stabilization of patients with ankylosing spinal disorder fractures remains a viable management method. Operative characteristics were similar between AS, DISH, and advanced spondylosis patients; however, DISH patients experienced a greater number of post-operative complications.
Threads of Practice: Enhanced Maternal and Child Health Nurses Working With Women Experiencing Family Violence
Authors: Adams Catina , Hooker Leesa , Taft Angela
Published: October 2021

Family violence is a serious public health issue with significant health consequences for women and children. Enhanced Maternal and Child Health nurses (EMCH) in Victoria, Australia, work with women experiencing family violence; however, scholarly examination of the clinical work of nurses has not occurred. This qualitative study explored how EMCH nurses work with women experiencing abuse, describing the personal and professional challenges for nurses undertaking family violence work. Twenty-five nurses participated in semi-structured interviews. Using interpretive description methodology has enabled an insight into nurses' family violence work. Threads of practice identified included (1) Validating/Reframing; (2) Non-judgmental support/Safeguarding and (3) Following/Leading. The nurses highlighted the diversity of experience for women experiencing abuse and nurses' roles in family violence nurse practice. The research contributes to understanding how EMCH nurses traverse threads of practice to support women experiencing family violence.
A gene expression–based model predicts outcome in children with intermediate-risk classical Hodgkin lymphoma
Authors: Johnston Rebecca L. , Mottok Anja , Chan Fong Chun , Jiang Aixiang , Diepstra Arjan , Visser Lydia , Telenius Adèle , Gascoyne Randy D. , Friedman Debra L. , Schwartz Cindy L. , Kelly Kara M. , Scott David W. , Horton Terzah M. , Steidl Christian
Published: October 2021

Classical Hodgkin lymphoma (cHL) is a common malignancy in children and adolescents. Although cHL is highly curable, treatment with chemotherapy and radiation often come at the cost of long-term toxicity and morbidity. Effective risk-stratification tools are needed to tailor therapy. Here, we used gene expression profiling (GEP) to investigate tumor microenvironment (TME) biology, to determine molecular correlates of treatment failure, and to develop an outcome model prognostic for pediatric cHL. A total of 246 formalin-fixed, paraffin-embedded tissue biopsies from patients enrolled in the Children’s Oncology Group trial AHOD0031 were used for GEP and compared with adult cHL data. Eosinophil, B-cell, and mast cell signatures were enriched in children, whereas macrophage and stromal signatures were more prominent in adults. Concordantly, a previously published model for overall survival prediction in adult cHL did not validate in pediatric cHL. Therefore, we developed a 9-cellular component model reflecting TME composition to predict event-free survival (EFS). In an independent validation cohort, we observed a significant difference in weighted 5-year EFS between high-risk and low-risk groups (75.2% vs 90.3%; log-rank P = .0138) independent of interim response, stage, fever, and albumin. We demonstrate unique disease biology in children and adolescents that can be harnessed for risk-stratification at diagnosis. This trial was registered at www.clinicaltrials.gov as #NCT00025259.
Severe impairment of T-cell responses to BNT162b2 immunization in patients with multiple myeloma
Authors: Enßle Julius C. , Campe Julia , Schwenger Amelie , Wiercinska Eliza , Hellstern Helen , Dürrwald Ralf , Rieger Michael A. , Wolf Sebastian , Ballo Olivier , Steffen Björn , Serve Hubert , Bonig Halvard , Rabenau Holger F. , Widera Marek , Ciesek Sandra , Metzler Ivana von , Ullrich Evelyn
Published: October 2021

Three reports address the protection of the vulnerable population of patients with hematologic malignancies in the face of the ongoing COVID pandemic. The reports suggest that some patients who fail to mount a B-cell response to vaccine may nevertheless have protective T cell responses. As a group, these reports suggest that patients should continue to be immunized with additional doses to attempt to improve immune response but that they need to maintain the precautions recommended for the unvaccinated.
Clonal phylogeny and evolution of critical cytogenetic aberrations in multiple myeloma at single-cell level by QM-FISH
Authors: Yan Yuting , Qin Xiaoqi , Liu Jiahui , Fan Huishou , Yan Wenqiang , Liu Lanting , Du Chenxing , Yu Zhen , Xu Yan , Hao Mu , Deng Shuhui , Sui Weiwei , Lyu Rui , Liu Wei , Wang Qi , Zou Dehui , Hu Linping , Wang Jianxiang , Tai Yu-Tzu , Anderson Kenneth C. , Zhang Lei , Cheng Tao , Zetterberg Anders , Munshi Nikhil C. , Qiu Lugui , An Gang
Published: October 2021

Single-cell analysis is of significant importance in delineating the exact phylogeny of the subclonal population and in discovering subtle diversification. So far, studies of intratumor heterogeneity and clonal evolution in multiple myeloma (MM) were largely focused on the bulk tumor population level. We performed quantitative multigene fluorescence in situ hybridization (QM-FISH) in 129 longitudinal samples of 57 MM patients. All the patients had newly diagnosed and relapsed paired samples. An expanded cohort of 188 MM patients underwent conventional FISH (cFISH) to validate the cytogenetic evolution in bulk tumor level. Forty-three of 57 patients (75.4%) harbored 3 or 4 cytogenetic clones at diagnosis. We delineated the phylogeny of the subclonal tumor population and derived the evolutionary architecture in each patient. Patients with clonal stabilization had a significantly improved overall survival (OS) than those with other evolutionary patterns (median OS, 71.2 months vs 39.7 months vs 35.2 months vs 25.5 months, for stable, differential, branching, and linear patterns, respectively; P = .001). A high degree of consistency and complementarity across QM-FISH and cFISH was observed in the evaluation of cytogenetic evolution patterns in MM. Survival after relapse was greater influenced by the presence of high-risk aberrations at relapse (hazard ratio = 2.07) rather than present at diagnosis (hazard ratio = 1.55). This study shows that QM-FISH is a valuable tool to elucidate the clonal architecture at the single-cell level. Clonal evolution pattern is of prognostic significance, highlighting the need for repeated cytogenetic evaluation in relapsed MM.
Modulating endothelial cells with EGFL7 to diminish aGVHD after allogeneic bone marrow transplantation in mice
Authors: Dorrance Adrienne M. , Moutuou Moutuaata M. , Goda Chinmayee , Sell Natalie E. , Kalyan Sonu , Karunasiri Malith , Kulkarni Rohan , Goulard Marie , Kolovich Sofia , Rudich Alexander , Naumann Eric , Ackaoui Antoine , Bigras Charles-Etienne , Daudelin Francis , Garzon Ramiro , Ranganathan Parvathi , Guimond Martin
Published: October 2021

Acute graft-versus-host disease (aGVHD) is the second most common cause of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT), underscoring the need for novel therapies. Based on previous work that endothelial cell dysfunction is present in aGVHD and that epidermal growth factor-like domain 7 (EGFL7) plays a significant role in decreasing inflammation by repressing endothelial cell activation and T-cell migration, we hypothesized that increasing EGFL7 levels after allo-HSCT will diminish the severity of aGVHD. Here, we show that treatment with recombinant EGFL7 (rEGFL7) in 2 different murine models of aGVHD decreases aGVHD severity and improves survival in recipient mice after allogeneic transplantation with respect to controls without affecting graft-versus-leukemia effect. Furthermore, we showed that rEGFL7 treatment results in higher thymocytes, T, B, and dendritic cell counts in recipient mice after allo-HSCT. This study constitutes a proof of concept of the ability of rEGFL7 therapy to reduce GHVD severity and mortality after allo-HSCT.
Retrospective epidemiological study of urolithiasis in western Algeria over a period of 50 years
Authors: Sbahi Khayra , Kacem Brahim , Talhi Randa , Azaiz Aicha , Attar Abderahmane , Addou Ahmed
Published: October 2021

Background

Urolithiasis is a pathology that changes with time and with the evolution of human societies. The prevalence of this pathology has gradually increased during the last decades, especially because of dietary changes.

Methods

This work is a retrospective descriptive epidemiological study of the temporal type carried out at the level of the urology service of the University Hospital Center of Oran between the first January 1965 and December 31, 2014. The objectives of this work are to study the epidemiological profile of urolithiasis and to determine the evolutionary trend of the disease over time.

Results

This study confirms some current data in the direction of an increase in surgical activity concerning the treatment of urinary stones. The analysis over time shows us a significant decrease (p < 0.01) in the male predominance between 1965 and 2014 with a M/F ratio which decreased from 3.09 to 1.82, as well as an increase in the average age, rising from 28.8 years in the period 1965–1974 to 48.3 years between 2005 and 2014.

Conclusion

The analysis of epidemiological data is essential to better evaluate the evolution of the urolithiasis disease, which was affirmed in our study, where a constant evolution of the characteristics of the disease was revealed, testifying the change of the socio-economic level in Algeria.
CL-ACP: a parallel combination of CNN and LSTM anticancer peptide recognition model
Authors: Wang Huiqing , Zhao Jian , Zhao Hong , Li Haolin , Wang Juan
Published: October 2021

Background

Anticancer peptides are defence substances with innate immune functions that can selectively act on cancer cells without harming normal cells and many studies have been conducted to identify anticancer peptides. In this paper, we introduce the anticancer peptide secondary structures as additional features and propose an effective computational model, CL-ACP, that uses a combined network and attention mechanism to predict anticancer peptides.

Results

The CL-ACP model uses secondary structures and original sequences of anticancer peptides to construct the feature space. The long short-term memory and convolutional neural network are used to extract the contextual dependence and local correlations of the feature space. Furthermore, a multi-head self-attention mechanism is used to strengthen the anticancer peptide sequences. Finally, three categories of feature information are classified by cascading. CL-ACP was validated using two types of datasets, anticancer peptide datasets and antimicrobial peptide datasets, on which it achieved good results compared to previous methods. CL-ACP achieved the highest AUC values of 0.935 and 0.972 on the anticancer peptide and antimicrobial peptide datasets, respectively.

Conclusions

CL-ACP can effectively recognize antimicrobial peptides, especially anticancer peptides, and the parallel combined neural network structure of CL-ACP does not require complex feature design and high time cost. It is suitable for application as a useful tool in antimicrobial peptide design.
Measuring the ratio of femoral vein diameter to femoral artery diameter by ultrasound to estimate volume status
Authors: Ma Zhihang , Gai Jiaxin , Sun Yinghan , Bai Yunpeng , Cai Hongyi , Wu Lei , Sun Lixiu , Liu Junyan , Xue Li , Liu Bingchen
Published: October 2021

Background

Currently, the accepted effective method for assessing blood volume status, such as measuring central venous pressure (CVP) and mean pulmonary artery pressure (mPAP), is invasive. The purpose of this study was to explore the feasibility and validity of the ratio of the femoral vein diameter (FVD) to the femoral artery diameter (FAD) for predicting CVP and mPAP and to calculate the cut-off value for the FVD/FAD ratio to help judge a patient’s fluid volume status.

Methods

In this study, 130 patients were divided into two groups: in group A, the FVD, FAD, and CVP were measured, and in group B, the FVD, FAD, and mPAP were measured. We measured the FVD and FAD by ultrasound. We monitored CVP by a central venous catheter and mPAP by a Swan-Ganz floating catheter. Pearson correlation coefficients were calculated. The best cut-off value for the FVD/FAD ratio for predicting CVP and mPAP was obtained according to the receiver operating characteristic (ROC) curve.

Results

The FVD/FAD ratio was strongly correlated with CVP (R = 0.87, P < 0.0000) and mPAP (R = 0.73, P < 0.0000). According to the ROC curve, an FVD/FAD ratio ≥ 1.495 had the best test characteristics to predict a CVP ≥ 12 cmH2O, and an FVD/FAD ratio ≤ 1.467 had the best test characteristics to predict a CVP ≤ 10 cmH2O. An FVD/FAD ratio ≥ 2.03 had the best test characteristics to predict an mPAP ≥ 25 mmHg. According to the simple linear regression curve of the FVD/FAD ratio and CVP, when the predicted CVP ≤ 5 cmH2O, the FVD/FAD ratio was ≤ 0.854.

Conclusion

In this study, the measurement of the FVD/FAD ratio obtained via ultrasound was strongly correlated with CVP and mPAP, providing a non-invasive method for quickly and reliably assessing blood volume status and providing good clinical support.
Optimising personal continuity for older patients in general practice: a study protocol for a cluster randomised stepped wedge pragmatic trial
Authors: Groot Lex J. J. , Schers Henk J. , Burgers Jako S. , Schellevis Francois G. , Smalbrugge Martin , Uijen Annemarie A. , van de Ven Peter M. , van der Horst Henriëtte E. , Maarsingh Otto R.
Published: October 2021

Background

Continuity of care, in particular personal continuity, is a core principle of general practice and is associated with many benefits such as a better patient-provider relationship and lower mortality. However, personal continuity is under pressure due to changes in society and healthcare. This affects older patients more than younger patients. As the number of older patients will double the coming decades, an intervention to optimise personal continuity for this group is highly warranted.

Methods

Following the UK Medical Research Council framework for complex Interventions, we will develop and evaluate an intervention to optimise personal continuity for older patients in general practice. In phase 0, we will perform a literature study to provide the theoretical basis for the intervention. In phase I we will define the components of the intervention by performing surveys and focus groups among patients, general practitioners, practice assistants and practice nurses, concluded by a Delphi study among members of our group. In phase II, we will test and finalise the intervention with input from a pilot study in two general practices. In phase III, we will perform a stepped wedge cluster randomised pragmatic trial. The primary outcome measure is continuity of care from the patients’ perspective, measured by the Nijmegen Continuity Questionnaire. Secondary outcome measures are level of implementation, barriers and facilitators for implementation, acceptability and feasibility of the intervention. In phase IV, we will establish the conditions for large-scale implementation.

Discussion

This is the first study to investigate an intervention for improving personal continuity for older patients in general practice. If proven effective, our intervention will enable General practitioners to improve the quality of care for their increasing population of older patients. The pragmatic design of the study will enable evaluation in real-life conditions, facilitating future implementation.

Trial registration number

Netherlands Trial Register, trial NL8132. Registered 2 November 2019.
Challenges and visions for managing pain-related insomnia in primary care using the hybrid CBT approach: a small-scale qualitative interview study with GPs, nurses, and practice managers
Authors: Collard V. E. J. , Moore C. , Nichols V. , Ellard D. R. , Patel S. , Sandhu H. , Parsons H. , Sharma U. , Underwood M. , Madan J. , Tang N. K. Y.
Published: October 2021

Background

Chronic pain and insomnia have a complex, bidirectional relationship – addressing sleep complaints alongside pain may be key to alleviating patient-reported distress and disability. Healthcare professionals have consistently reported wanting to offer psychologically informed chronic pain management at the primary care level. Research in secondary care has demonstrated good treatment efficacy of hybrid CBT for chronic pain and insomnia. However, primary care is typically the main point of treatment entry, hence may be better situated to offer treatments using a multidisciplinary approach. In this study, primary care service providers’ perception of feasibility for tackling pain-related insomnia in primary care was explored.

Methods

The data corpus originates from a feasibility trial exploring hybrid CBT for chronic pain and insomnia delivered in primary care. This formed three in-depth group interviews with primary care staff (n = 9) from different primary care centres from the same NHS locale. All interviews were conducted on-site using a semi-structured approach. Verbal data was recorded, transcribed verbatim and analysed using the thematic analysis process.

Results

Eight themes were identified – 1) Discrepant conceptualisations of the chronic pain-insomnia relationship and clinical application, 2) Mismatch between patients’ needs and available treatment offerings, 3) Awareness of psychological complexities, 4) Identified treatment gap for pain-related insomnia, 5) Lack of funding and existing infrastructure for new service development, 6) General shortage of psychological services for complex health conditions, 7) Multidisciplinary team provision with pain specialist input, and 8) Accessibility through primary care. These mapped onto four domains - Current understanding and practice, Perceived facilitators, Perceived barriers, Ideal scenarios for a new treatment service – which reflected the focus of our investigation. Taken together these provide key context for understanding challenges faced by health care professionals in considering and developing a new clinical service.

Conclusions

Primary care service providers from one locale advocate better, multidisciplinary treatment provision for chronic pain and insomnia. Findings suggest that situating this in primary care could be a feasible option, but this requires systemic support and specialist input as well as definitive trials for success.
Regorafenib combined with transarterial chemoembolization for unresectable hepatocellular carcinoma: a real-world study
Authors: Han Yue , Cao Guang , Sun Bin , Wang Jian , Yan Dong , Xu Haifeng , Shi Qinsheng , Liu Zechuan , Zhi Weihua , Xu Liang , Liu Bojun , Zou Yinghua
Published: October 2021

Background

The benefits and tolerability of transarterial chemoembolization (TACE) combined with regorafenib as a second-line therapy has not been reported for unresectable hepatocellular carcinoma (HCC). This study aimed to explore the benefits and tolerability of TACE combined with second-line regorafenib in patients with unresectable advanced HCC and failure to first-line treatment.

Methods

This was a multicenter retrospective study of patients with progression after first-line sorafenib and/or lenvatinib between 01/2019 and 04/2020 at four tertiary hospitals in China. The patients were treated with TACE. Then, 5–7 days after the first TACE, the patients started taking regorafenib for 3 weeks every 4-week cycle. The overall survival (OS), time to progression (TTP), progression-free survival (PFS), and adverse events (AEs) were observed.

Results

The median follow-up was 5.6 (range 0.7, 17.0) months. The median age was 60 (range 35, 79) years. There were 32 (84.2%) males. The patients underwent a median of three TACE sessions (range 1–13). The initial doses of regorafenib were 20 mg/d (n = 1, 2.6%), 80 mg/d (n = 10, 26.3%), 120 mg/d (n = 15, 39.5%), and 160 mg/d (n = 11, 28.9%). The incidence of grade 3/4 AEs was 15.8%. Two patients stopped regorafenib due to AEs. The median OS was 14.3 months. The median PFS and TTP were 9.1 (95% CI 4.0, 14.2) and 9.1 (95% CI 5.5, 12.8) months, respectively.

Conclusions

The present study provides real-world evidence indicating that regorafenib combined with TACE was beneficial and tolerable in patients with unresectable HCC. Additional prospective large-scale studies are required for confirmation.
Risk and characteristics of tuberculosis after anti-tumor necrosis factor therapy for inflammatory bowel disease: a hospital-based cohort study from Korea
Authors: Lee Jae Yong , Oh Kyunghwan , Hong Hee Seung , Kim Kyuwon , Hong Seung Wook , Park Jin Hwa , Hwang Sung Wook , Yang Dong-Hoon , Ye Byong Duk , Byeon Jeong-Sik , Myung Seung-Jae , Yang Suk-Kyun , Lee Ho-Su , Jo Kyung-Wook , Park Sang Hyoung
Published: October 2021

Background

Anti-tumor necrosis factor (TNF) treatment for inflammatory bowel disease (IBD) increases the risk of tuberculosis (TB) infection. In the present study, we analyzed the clinical characteristics and risks of TB in Korean patients with IBD who received anti-TNF treatment.

Methods

The study included patients with IBD who were treated using anti-TNF agents between January 2001 and June 2018 at the Asan Medical Center. Overall, 1434 patients with ulcerative colitis or Crohn’s disease were enrolled. We calculated the incidence of active TB infection after anti-TNF treatment and compared the clinical characteristics of the TB group with those of the non-TB group.

Results

Twenty-one patients (1.46%) developed active TB infection, and the incidence rate of active TB was 366.73 per 100,000 person-years. In total, 198 patients (14.9%) were positive for latent tuberculosis infection (LTBI), of whom only eight (4%) did not complete LTBI treatment. The age at which the anti-TNF therapy was started was significantly higher in the TB group than in the non-TB group (HR 1.041, 95% CI 1.014–1.069, p = 0.002), and as age increased, so did the incidence rate of active TB infection (linearity p < 0.001). There was no significant difference in the incidence rate of LTBI between the TB and non-TB groups (HR 0.896, 95% CI 0.262–3.066, p = 0.862).

Conclusions

In patients with IBD, the incidence rate of TB increased with age at anti-TNF therapy initiation. Active treatment of LTBI may lower the incidence of TB in patients with IBD who are to undergo anti-TNF therapy.
Plasma leakage in dengue: a systematic review of prospective observational studies
Authors: Rodrigo Chaturaka , Sigera Chathurani , Fernando Deepika , Rajapakse Senaka
Published: October 2021

Plasma leakage is a precursor to life-threatening complications of dengue, but this group is poorly defined and not often reported in literature. Patients with Dengue haemorrhagic fever (DHF) as defined in the 1997 World Health Organization classification are often reported, and they all have plasma leakage, but some patients with plasma leakage do not meet the definition of DHF. The study aims to estimate the frequency of plasma leakage and DHF (as a surrogate of plasma leakage) in dengue and its variations based on virus serotype, geography, patient gender and pre-existing immunity to dengue. PUBMED, Scopus, EMBASE, CINAHL and Web of Science were searched for prospective observational studies reporting on plasma leakage or DHF. Quality of data was assessed using the NIH quality assessment tool for cohort studies. Forty-three studies that recruited 15,794 confirmed dengue patients were eligible. Cumulative frequency of plasma leakage was 36.8% (15 studies, 1642/4462, 95% CI 35.4–38.2%), but surprisingly the estimated cumulative frequency of DHF was higher (45.7%, 32 studies, 4758/10417, 95% CI 44.7–46.6%), indicating that current medical literature over-reports DHF or under-reports plasma leakage. Therefore, a reliable estimate for the proportion of dengue patients developing plasma leakage cannot be derived from existing medical literature even after applying rigorous inclusion criteria to select homogenous studies. Plasma leakage is an important marker of “at-risk” dengue patients and standardizing its definition, diagnosis and reporting should be a priority in research and global policy.
A de novo variant of POLR3B causes demyelinating Charcot-Marie-Tooth disease in a Chinese patient: a case report
Authors: Xue Yan-Yan , Cheng Hao-Ling , Dong Hai-Lin , Yin Hou-Min , Yuan Yun , Meng Ling-Chao , Wu Zhi-Ying , Yu Hao
Published: October 2021

Background

Charcot-Marie-Tooth (CMT) disease is a group of inherited peripheral neuropathies, which are subdivided into demyelinating and axonal forms. Biallelic mutations in POLR3B are the well-established cause of hypomyelinating leukodystrophy, which is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. To date, only one study has reported the demyelinating peripheral neuropathy phenotype caused by heterozygous POLR3B variants.

Case presentation

A 19-year-old male patient was referred to our hospital for progressive muscle weakness of the lower extremities. Physical examination showed muscle atrophy, sensory loss and deformities of the extremities. Nerve conduction studies and electromyography tests revealed sensorimotor demyelinating polyneuropathy with secondary axonal loss. Trio whole-exome sequencing revealed a de novo variant in POLR3B (c.3137G > A).

Conclusions

In this study, we report the case of a Chinese patient with a de novo variant in POLR3B (c.3137G > A), who manifested demyelinating CMT phenotype without additional neurological or extra-neurological involvement. This work is the second report on POLR3B-related CMT.
Effects of dezocine on morphine tolerance and opioid receptor expression in a rat model of bone cancer pain
Authors: Wu Lin-xin , Dong Yan-peng , Zhu Qian-mei , Zhang Bo , Ai Bo-lun , Yan Tao , Zhang Guo-hua , Sun Li
Published: October 2021

Background

Clinically, the coadministration of opioids to enhance antinociception and decrease tolerance has attracted increasing research attention. We investigated the effects of dezocine, a mu- and kappa-opioid receptor agonist/antagonist, on morphine tolerance and explored the involvement of opioid receptor expression in a rat model of bone cancer pain.

Methods

Thermal nociceptive thresholds were measured after the subcutaneous injection of morphine (10 mg/kg) alone or combined with dezocine (10 or 1 mg/kg) for 7 consecutive days. Real-time PCR and western blot analysis were used to examine opioid receptor expression in the periaqueductal gray (PAG) and spinal cord.

Results

The analgesic effect was significantly decreased after 4 days of morphine administration. We observed that low-dose dezocine significantly attenuated morphine tolerance without reducing the analgesic effect of morphine. Low-dose dezocine coadministration significantly reversed the downregulated expression of mu (MOR) and delta (DOR) opioid receptors in the PAG and the upregulated expression of kappa (KOR) and DOR in the spinal cord induced by morphine. Moreover, low-dose dezocine coadministered with morphine significantly inhibited KOR expression in both the PAG and spinal cord.

Conclusions

The combination of low-dose dezocine with morphine may prevent or delay the development of morphine tolerance in a rat model of bone cancer pain. The regulation of opioid receptor expression in the PAG and spinal cord may be part of the mechanism.
Pembrolizumab plus lenvatinib with or without hepatic arterial infusion chemotherapy in selected populations of patients with treatment-naive unresectable hepatocellular carcinoma exhibiting PD-L1 staining: a multicenter retrospective study
Authors: Chen Song , Xu Bo , Wu Zhiqiang , Wang Pengfei , Yu Weiguang , Liu Zhiyong , Huang Xiaoyong , Wu Yanqing , Li Tengfei , Guo Wenbo
Published: October 2021

Background

Not all patients with unresectable hepatocellular carcinoma (uHCC) benefit from treatment with immune checkpoint inhibitors and molecular-targeted agents. The aim of this retrospective study was to assess the efficacy and safety of pembrolizumab plus lenvatinib plus hepatic arterial infusion chemotherapy (HAIC) versus pembrolizumab plus lenvatinib in selected populations of patients with treatment-naive uHCC exhibiting programmed cell death ligand-1 (PD-L1) staining.

Methods

Consecutive patients with treatment-naive uHCC exhibiting PD-L1 staining who were treated with pembrolizumab plus lenvatinib plus HAIC (PLH) or pembrolizumab plus lenvatinib (PL) were retrospectively identified from our medical centres from 2018 to 2021. HAIC involved oxaliplatin, fluorouracil, and leucovorin (FOLFOX). Follow-up occurred every 3 weeks for 1 year and then every 6 weeks thereafter. The primary endpoints included overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the frequency of key adverse events (AEs).

Results

In total, 248 treatment-naive patients were retrospectively reviewed, 78 of whom were ineligible on the basis of the current criteria. Thus, 170 patients (PLH: n = 84, median age 52 years [range, 42–67]; PL: n = 86, 53 years [range, 43–69]) were eligible for the analysis. The median follow-up was 18.6 months (range, 1–26). At the final follow-up, the median OS was 17.7 months (95% confidence interval [CI], 15.2–18.3) in the PLH group versus 12.6 months (95% CI, 11.1–13.7) in the PL group (hazard ratio [HR] 0.52; 95% CI, 0.36–0.75; p = 0.001). A significant difference was also detected in the median PFS (10.9 months [95% CI, 8.7–11.4] for PLH vs. 6.8 months (95% CI, 5.2–7.4) for PL; HR 0.61, 95% CI, 0.43–0.85; p = 0.001). Significant differences in the rate of the key AEs were noted between groups (79.8% for PLH vs. 62.8% for PL, p = 0.015), but these AEs were controllable.

Conclusions

Among selected populations of patients with treatment-naive uHCC exhibiting PD-L1 staining, the PLH regimen may substantially improve the survival benefits compared with the PL regimen with a controllable safety profile.
When in doubt, Google it: distress-related information seeking in Italy during the COVID-19 pandemic
Authors: Monzani Dario , Vergani Laura , Marton Giulia , Pizzoli Silvia F. M. , Pravettoni Gabriella
Published: October 2021

Background

Psychological health has been one of the aspects affected by the recent COVID-19 pandemic. We aim to evaluate the patterns of Google search for mental distress symptoms of Italian citizens during the various phases of the COVID-19 pandemic.

Methods

We assessed Google searches for psychological-health related words. We gathered and analyzed data on daily search queries on depression, anxiety, and insomnia from Google Trends, in a time ranging from the Pre-COVID phase (beginning 25th January 2020) up to the second wave phase (ending 17th October 2020). We performed three general linear models on search trends of the three words and tested whether and to what extent official data about new cases of COVID-19, information searching on new cases, and the government health measures impacted on these trends.

Results

Average daily search queries were higher for anxiety, followed by depression and insomnia. General linear models performed to assess differences in daily search queries for anxiety, depression and insomnia were significant, respectively [F(13, 253) = 6.80, P < .001]; [F(13, 253) = 10.25, P < .001]; [F(13, 253) = 6.61, P < .001].

Specifically, daily search queries differed among different phases of managing the COVID-19 outbreak: anxiety [F(5, 253) = 10.35, P < .001, $$ {n}_p^2 $$

n
p
2

= .17]; depression [F(5, 253) = 13.59, P < .001, $$ {n}_p^2 $$

n
p
2

= .21]; insomnia [F(5, 253) = 3.52, P = .004, $$ {n}_p^2 $$

n
p
2

= .07].

Conclusions

Our study contributed to the investigation of online information-seeking behaviors of Italians regarding mental health throughout the entire phase of the pandemic and provides insights on the possible future trends of mental distress during upcoming pandemic phases.
Cone beam CT augmented fluoroscopy allows safe and efficient diagnosis of a difficult lung nodule
Authors: Piro Roberto , Fontana Matteo , Casalini Eleonora , Taddei Sofia , Bertolini Marco , Iori Mauro , Facciolongo Nicola
Published: October 2021

Background

Detection of small peripheral lung nodules is constantly increasing with the development of low dose computed tomography lung cancer screening programs. A tissue diagnosis is often required to confirm malignity, with endobronchial biopsies being associated with a lower pneumothorax rate than percutaneous approaches. Endoscopic diagnosis of peripheral small size lung nodules is however often challenging using traditional bronchoscopy and endobronchial ultrasound alone. New virtual bronchoscopic navigation techniques such as electromagnetic navigational bronchoscopy (ENB) have developed to improve peripheral navigation, with diagnostic yield however remaining in the 30–50% range for small lesions. Recent studies have shown the benefits of combining Cone beam computed tomography (CBCT) with ENB to improve diagnostic yield to up to 83%. The use of ENB however remains limited by disposable cost, bronchus sign dependency and inaccuracies due to CT to body divergence.

Case presentation

This case report highlights the feasibility and usefulness of CBCT-guided bronchoscopy for the sampling of lung nodules difficult to reach through traditional bronchoscopy because of nodule size and peripheral position. Procedure was scheduled in a mobile robotic hybrid operating room with patient under general anaesthesia. CBCT acquisition was performed to localize the target lesion and plan the best path to reach it into bronchial tree. A dedicated software was used to segment the lesion and the bronchial path which 3D outlines were automatically fused in real time on the fluoroscopic images to augment live guidance. Navigation to the lesion was guided with bronchoscopy and augmented fluoroscopy alone. Before the sampling, CBCT imaging was repeated to confirm the proper position of the instrument into the lesion. Four transbronchial needle aspirations (TBNA) were performed and the tissue analysis showed a primary lung adenocarcinoma.

Conclusions

CBCT and augmented fluoroscopy technique is a safe and effective and has potential to improve early stage peripheral lesions endobronchial diagnostic yield without ENB. Additional studies are warranted to confirm its safety, efficacy and technical benefits, both for diagnosis of oncological and non-oncological disease and for endobronchial treatment of inoperable patients.
Inguinal hernia repair in inpatient children: a nationwide analysis of German administrative data
Authors: Heydweiller Andreas , Kurz Ralf , Schröder Arne , Oetzmann von Sochaczewski Christina
Published: October 2021

Background

Contrary to adult inguinal hernia surgery, large-scale investigations using registries or administrative data are missing in paediatric surgery. We aimed to fill this gap by analysing German administrative hospital data to describe the current reality of inpatient hernia surgery in children.

Methods

We analysed aggregated data files bought from the German federals statistics office on hospital reimbursement data separately for principal diagnoses of inguinal hernia in children and for herniotomies in inpatients. Developments over time were assessed via regression and differences between groups with nonparametric comparisons.

Results

Principal diagnoses of hernias were decreasing over time with the exception of male bilateral and female bilateral incarcerated hernias in the first year of life which increased. The vast majority of operations were conducted via the open approach and laparoscopy was increasingly only used for females older than 1 year of age. Recurrent hernia repair was scarce. Rates of inguinal hernia repair were higher in both sexes the younger the patient was, but were also decreasing in all age groups despite a population growth since 2012. The amount of inguinal hernia repairs by paediatric surgeons compared to adult surgeons increased by 1.5% per year.

Conclusions

Our results corroborate previous findings of age and sex distribution. It demonstrates that inpatient hernia repair is primarily open surgery with herniorrhaphy and that recurrences seem to be rare. We observed decreasing rates of hernia repairs over time and as this has been described before in England, future studies should try to elucidate this development.

Level of evidence

III.
Heart failure as a serious complication of iodinated contrast-induced hyperthyroidism: case-report
Authors: Diepenbroek Sofie M. , de Jonghe A. , van Rees C. , Seebus E.
Published: October 2021

Background

exposure to iodinated contrast media (ICM) can cause hyperthyroidism, due to disruption of thyroid hormone regulation. Although rare, it can have severe consequences and can lead to fatal complications. Current guidelines do not recommend standard laboratory testing of the thyroid function prior to ICM exposure. Prophylactic treatment of patients at higher risk of hyperthyroidism is not advised.

Case presentation

we report the case of an 82-year-old woman who developed ICM induced hyperthyroidism after undergoing a chest computed tomography (CT). One month after ICM administration she presented with pneumonia at the emergency department. Hyperthyroidism was found with concomitant tachycardia, which was hard to control. As a result of hyperthyroidism and coincidental pneumonia the patient developed heart failure and died of myocardial ischemia.

Conclusions

this case report underlines the importance of close monitoring of high-risk patients after ICM exposure. Clinicians should be aware of the risk of hyperthyroidism and potential severe complications. The use of ICM needs careful consideration, especially in the elderly who suffer more often from multinodular goitre.
The association of dietary diabetes risk reduction score and its components with risk of metabolic syndrome incident in Tehranian adults
Authors: Mirmiran Parvin , Farhadnejad Hossein , Teymoori Farshad , Asghari Golaleh , Parastouei Karim , Azizi Fereidoun
Published: October 2021

Background

Evidence of possible beneficial effects of dietary diabetes risk reduction score (DDRRS) on reducing the risk of various chronic diseases such as metabolic syndrome (MetS) are limited. This is a prospective, population-based cohort study, which aimed to investigate the relationship of the DDRRS and its components with MetS incident in Iranian adults.

Methods

Individuals without MetS (n=3561) were recruited from participants of the Tehran Lipid and Glucose Study (2009-2011) and followed for a mean of 6.01 years. A validated food frequency questionnaire was used to determine the DDRRS using based on eight components, including higher intakes of cereal fiber, nuts, coffee, and polyunsaturated: saturated fat ratio and lower intakes of red or processed meats, sugar-sweetened beverages, trans fatty acids, and low glycemic index. We used the multivariable logistic regression analysis to determine the odds ratio (ORs) and 95 % confidence interval (CI) of MetS across the tertiles of DDRRS.

Results

The mean (SD) age of individuals was 38.1(12.6) years at baseline. Median (25-75 interquartile range) DDRRS for all participants was 20(18-22). During the study follow-up, 682(19.1 %) new cases of MetS were reported. Based on the age and sex-adjusted model, participants in highest tertile of DDRRS had lower risk of MetS in compared with the lowest one (OR=0.64;95 %CI:0.52-0.79, P for trend=0.001). In the multivariable adjusted model, after adjustment for all possible confounding variables, the risk of MetS is decreased across tertiles of DDRRS (OR=0.60;95 %CI:0.48-0.75, P for trend=0.001). Also, higher scores of some DDRRS components including red and processed meat, sugar sweetened beverages, and coffee were related to decreased incidence of MetS.

Conclusions

The results of this study revealed that greater adherence to DDRRS can be associated with decreased risk of MetS in Iranian adult.
Predictive modeling for 14-day unplanned hospital readmission risk by using machine learning algorithms
Authors: Lo Yu-Tai , Liao Jay Chiehen , Chen Mei-Hua , Chang Chia-Ming , Li Cheng-Te
Published: October 2021

Background

Early unplanned hospital readmissions are associated with increased harm to patients, increased medical costs, and negative hospital reputation. With the identification of at-risk patients, a crucial step toward improving care, appropriate interventions can be adopted to prevent readmission. This study aimed to build machine learning models to predict 14-day unplanned readmissions.

Methods

We conducted a retrospective cohort study on 37,091 consecutive hospitalized adult patients with 55,933 discharges between September 1, 2018, and August 31, 2019, in an 1193-bed university hospital. Patients who were aged < 20 years, were admitted for cancer-related treatment, participated in clinical trial, were discharged against medical advice, died during admission, or lived abroad were excluded. Predictors for analysis included 7 categories of variables extracted from hospital’s medical record dataset. In total, four machine learning algorithms, namely logistic regression, random forest, extreme gradient boosting, and categorical boosting, were used to build classifiers for prediction. The performance of prediction models for 14-day unplanned readmission risk was evaluated using precision, recall, F1-score, area under the receiver operating characteristic curve (AUROC), and area under the precision–recall curve (AUPRC).

Results

In total, 24,722 patients were included for the analysis. The mean age of the cohort was 57.34 ± 18.13 years. The 14-day unplanned readmission rate was 1.22%. Among the 4 machine learning algorithms selected, Catboost had the best average performance in fivefold cross-validation (precision: 0.9377, recall: 0.5333, F1-score: 0.6780, AUROC: 0.9903, and AUPRC: 0.7515). After incorporating 21 most influential features in the Catboost model, its performance improved (precision: 0.9470, recall: 0.5600, F1-score: 0.7010, AUROC: 0.9909, and AUPRC: 0.7711).

Conclusions

Our models reliably predicted 14-day unplanned readmissions and were explainable. They can be used to identify patients with a high risk of unplanned readmission based on influential features, particularly features related to diagnoses. The operation of the models with physiological indicators also corresponded to clinical experience and literature. Identifying patients at high risk with these models can enable early discharge planning and transitional care to prevent readmissions. Further studies should include additional features that may enable further sensitivity in identifying patients at a risk of early unplanned readmissions.