bluuebunny/crossref_metadata_2025 huggingface dataset:
Brodalumab for Treatment-Resistant Psoriasis: Case Reports and Safety Update
Authors: Brownstone Nicholas D. , Reddy Vidhatha , Thibodeaux Quinn , Chan Stephanie , Myers Bridget , Bhutani Tina , Koo John Y. M.
Published: May 2020

Introduction:

Brodalumab is an interleukin-17 receptor blocker that is effective for the treatment of psoriasis. However, due to a Food and Drug Administration black box warning on depression and suicide, many providers are hesitant to use this agent despite its efficacy.

Methods:

We present the cases of 2 brothers seen at our clinic with treatment-resistant psoriasis who were both successfully treated with brodalumab, despite failing 6 other biologics. We also review the safety profile of brodalumab regarding the currently available evidence on the increased risk of suicidality or depression in patients treated with brodalumab.

Results:

Both patients achieved completely clear skin and maintained clearance on brodalumab.

Discussion:

Brodalumab appears to be an effective agent in severe treatment-resistant cases of psoriasis. In addition, a causal relationship between increased risk of suicidality or depression and brodalumab use has not been established.
The multifaceted outcomes of community-engaged water quality management in a Palestinian refugee camp
Authors: Bishara Amahl , Al-Azraq Nidal , Alazzeh Shatha , Durant John L
Published: May 2020

The Palestinian residents of Aida Refugee Camp have lived under Israeli military occupation for over 50 years. While they struggle against the more legible concerns of the separation wall, unemployment, military violence, and high rates of incarceration, these residents are also acutely aware of a lack of adequate drinking water supplies. This led one young filmmaker, working at a small Palestinian non-governmental organization (NGO) in Aida, to produce a documentary in 2011 called Everyday Nakba, which suggests that for Palestinians, water scarcity is a continuation of the historical crisis of dispossession that began in 1948. This documentary ignited an interdisciplinary and multimodal collaboration among an environmental engineer, an environmental lawyer, an anthropologist, a Boston-based NGO, and the small Palestinian NGO to investigate problems of water quality that are related to water scarcity. This article—co-authored by members of the group of interdisciplinary scholars and NGO workers—reflects on our practice together to chronicle how small NGOs and interdisciplinary groups of community-engaged scholars can creatively approach multifaceted environmental problems, while also examining the limits of such approaches. Our collaboration has catalyzed water quality testing, point-of-use water treatment, rooftop gardens, awareness about water problems, political advocacy, and environmental education, though it has not been able to address the structural problem of inadequate supply of water. It has led to research that contributed to the literature on water intermittency. This article considers how this collaboration has shifted how members of a refugee community think about justice and the environment. Water concerns often demand a multifaceted and interdisciplinary approach because water scarcity has health, economic, social, and political implications. Our research team saw how interdisciplinary collaboration and a network of activists in the West Bank and the USA can lead to multifaceted—albeit modest—outcomes, even though military occupation presents stubborn barriers to major change.
Methodology for the American Society of Hematology VTE guidelines: current best practice, innovations, and experiences
Authors: Wiercioch Wojtek , Nieuwlaat Robby , Akl Elie A. , Kunkle Robert , Alexander Kendall E. , Cuker Adam , Rajasekhar Anita , Alonso-Coello Pablo , Anderson David R. , Bates Shannon M. , Cushman Mary , Dahm Philipp , Guyatt Gordon , Iorio Alfonso , Lim Wendy , Lyman Gary H. , Middeldorp Saskia , Monagle Paul , Mustafa Reem A. , Neumann Ignacio , Ortel Thomas L. , Rochwerg Bram , Santesso Nancy , Vesely Sara K. , Witt Daniel M. , Schünemann Holger J.
Published: May 2020

Background:

Methods for the development of clinical guidelines have advanced dramatically over the past 2 decades to strive for trustworthiness, transparency, user-friendliness, and rigor. The American Society of Hematology (ASH) guidelines on venous thromboembolism (VTE) have followed these advances, together with application of methodological innovations.

Objective:

In this article, we describe methods and methodological innovations as a model to inform future guideline enterprises by ASH and others to achieve guideline standards. Methodological innovations introduced in the development of the guidelines aim to address current challenges in guideline development.

Methods:

We followed ASH policy for guideline development, which is based on the Guideline International Network (GIN)-McMaster Guideline Development Checklist and current best practices. Central coordination, specialist working groups, and expert panels were established for the development of 10 VTE guidelines. Methodological guidance resources were developed to guide the process across guidelines panels. A methods advisory group guided the development and implementation of methodological innovations to address emerging challenges and needs.

Results:

The complete set of VTE guidelines will include >250 recommendations. Methodological innovations include the use of health-outcome descriptors, online voting with guideline development software, modeling of pathways for diagnostic questions, application of expert evidence, and a template manuscript for publication of ASH guidelines. These methods advance guideline development standards and have already informed other ASH guideline projects.

Conclusions:

The development of the ASH VTE guidelines followed rigorous methods and introduced methodological innovations during guideline development, striving for the highest possible level of trustworthiness, transparency, user-friendliness, and rigor.
ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma
Authors: Scherpereel Arnaud , Opitz Isabelle , Berghmans Thierry , Psallidas Ioannis , Glatzer Markus , Rigau David , Astoul Philippe , Bölükbas Servet , Boyd Jeanette , Coolen Johan , De Bondt Charlotte , De Ruysscher Dirk , Durieux Valerie , Faivre-Finn Corinne , Fennell Dean , Galateau-Salle Francoise , Greillier Laurent , Hoda Mir Ali , Klepetko Walter , Lacourt Aude , McElnay Phil , Maskell Nick A. , Mutti Luciano , Pairon Jean-Claude , Van Schil Paul , van Meerbeeck Jan P. , Waller David , Weder Walter , Cardillo Giuseppe , Putora Paul Martin
Published: May 2020

The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009–2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionallyviaimage-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, includingBAP-1andCDKN2A(p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pre-therapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.
Comparing national dementia plans and strategies in Europe – is there a focus of care for people with dementia from a migration background?
Authors: Schmachtenberg Tim , Monsees Jessica , Hoffmann Wolfgang , van den Berg Neeltje , Stentzel Ulrike , Thyrian Jochen René
Published: May 2020

Background

People with migration background and dementia are a vulnerable group. Providing care for this group is a public health challenge in Europe. An increasing number of countries are issuing national dementia plans, but a systematic overview of national dementia plans of European countries focusing on care for people with migration background is lacking. This study aims to illustrate how European countries identify the dementia-related needs of people with migration background and whether there are specific healthcare services for them at the national level.

Methods

A qualitative analysis of national dementia plans of the EU and EFTA (European Free Trade Association) countries was carried out. Using the discourse analysis model according to Rainer Keller (2011), documents were systematically screened for their relation to migration via keyword and context analysis. The content of the migration-related sections was analyzed using the methods of paraphrasing, memos, comments, and open coding.

Results

Twenty-three of the 35 EU and ETFA countries have a national dementia plan, ten of these documents refer to migration and one country (Austria) has a national dementia plan with a chapter on migration. Eight national dementia plans identify that people with migration background and dementia have special needs, and actions to care for this group are planned in nine countries. However, only Norway, Northern Ireland, and the Netherlands refer to available healthcare services for people with migration background. Overall, the topic of migration plays a subordinate role in the national dementia plans of European countries.

Conclusions

The current lack of migrant-specific healthcare services in almost all European countries may lead to denying the right to appropriate care to a growing population. The topic of migration must be given greater attention in national dementia plans. European countries should develop strategies with specific services that address the needs of people with migration background. To improve comparability at the European level, a common definition of migration is needed. Further studies should include country-specific problems related to dementia and migration.
Comparisons of perventricular device closure, conventional surgical repair, and transcatheter device closure in patients with perimembranous ventricular septal defects: a network meta-analysis
Authors: Li Dongxu , Zhou Xu , Li Mengsi , An Qi
Published: May 2020

Background

Treatments for perimembranous ventricular septal defects (pmVSD) mainly include conventional surgical repair (CSR), transcatheter device closure (TDC), and perventricular device closure (PDC). We aimed to perform a network meta-analysis to compare the three approaches in patients with pmVSD.

Methods

We searched for comparative studies on device closure and conventional repair for pmVSD to April 2020. A network meta-analysis was performed under the frequentist frame with risk ratio and 95% confidence interval. The main outcome was the procedural success rate. Additional outcomes were postoperative complications, including residual shunt, intra-cardiac conduction block, valvular insufficiency, incision infection, and pericardial effusion.

Results

Twenty-four studies of 8113 patients were included in the comparisons. The pooled estimates of success rate favored the CSR compared with the PDC. No significant differences of success rate were found in the TDC versus CSR and the PDC versus TDC. The pooled estimates of incidences of the residual shunt, new tricuspid regurgitation, incision infection, and pericardial effusion favored the PDC compared with the CSR. There were no significant differences between the PDC and TDC approaches in all outcomes except new aortic regurgitation.

Conclusion

The PDC technique not only reduces the risk of significant complications compared with the CSR, but also produces not inferior results compared with the TDC in selected pmVSD patients.

PROSPERO registration number

CRD42019125257.
Perceptions and experiences with district health information system software to collect and utilize health data in Bangladesh: a qualitative exploratory study
Authors: Begum Tahmina , Khan Shaan Muberra , Adamou Bridgit , Ferdous Jannatul , Parvez Muhammad Masud , Islam Mohammad Saiful , Kumkum Feroza Akhter , Rahman Aminur , Anwar Iqbal
Published: May 2020

Background

Accurate and high-quality data are important for improving program effectiveness and informing policy.

In 2009 Bangladesh’s health management information system (HMIS) adopted the District Health Information Software, Version 2 (DHIS2) to capture real-time health service utilization data. However, routinely collected data are being underused because of poor data quality and reporting. We aimed to understand the facilitators and barriers to implementing DHIS2 as a way to retrieve meaningful and accurate data for reproductive, maternal, newborn, child, and adolescent health (RMNCAH) services.

Methods

This qualitative study was conducted in two districts of Bangladesh from September 2017 to 2018. Data collection included key informant interviews (n = 11), in-depth interviews (n = 23), and focus group discussions (n = 2). The study participants were involved with DHIS2 implementation from the community level to the national level. The data were analyzed thematically.

Results

DHIS2 could improve the timeliness and completeness of data reporting over time. The reported facilitating factors were strong government commitment, extensive donor support, and positive attitudes toward technology among staff. Quality checks and feedback loops at multiple levels of data gathering points are helpful for minimizing data errors. Introducing a dashboard makes DHIS2 compatible to use as a monitoring tool. Barriers to effective DHIS2 implementation were lack of human resources, slow Internet connectivity, frequent changes to DHIS2 versions, and maintaining both manual and electronic system side-by-side. The data in DHIS2 remains incomplete because it does not capture data from private health facilities. Having two parallel HMIS reporting the same RMNCAH indicators threatens data quality and increases the reporting workload.

Conclusion

The overall insights from this study are expected to contribute to the development of effective strategies for successful DHIS2 implementation and building a responsive HMIS. Focused strategic direction is needed to sustain the achievements of digital data culture. Periodic refresher trainings, incentives for increased performance, and an automated single reporting system for multiple stakeholders could make the system more user-friendly. A national electronic health strategy and implementation framework can facilitate creating a culture of DHIS2 use for planning, setting priorities, and decision making among stakeholder groups.
Multilocus sequence typing characterizes diversity of Ureaplasma diversum strains, and intra-species variability induces different immune response profiles
Authors: Andrade Yasmin M. F. S. , Santos-Junior Manoel N. , Rezende Izadora S. , Barbosa Maysa S. , Amorim Aline T. , Silva Ícaro B. S. , Queiroz Ellunny C. , Bastos Bruno L. , Campos Guilherme B. , Timenetsky Jorge , Marques Lucas M.
Published: May 2020

Background

Ureaplasma diversum is a pathogen found in the genital tract of cattle and associated with genital disorders such as infertility, placentitis, abortion, birth of weak calves, low sperm motility, seminal vesiculitis and epididymitis. There are few studies evaluating the genetic diversity of U. diversum strains and their influence on the immune response in cattle. Therefore, to better understand genetic relationships of the pathogenicity of U. diversum, a multilocus sequence typing (MLST) scheme was performed to characterize the ATCC 49782 strain and another 40 isolates recovered from different Brazilian states.

Results

Primers were designed for housekeeping genes ftsH, polC, rpL22, rpoB, valS and ureA and for virulence genes, phospholipase D (pld), triacylglycerol lipase (tgl), hemolysin (hlyA), MIB-MIP system (mib,mip), MBA (mba), VsA (VsA) and ribose transporter (tABC). PCRs were performed and the targeted gene products were purified and sequenced. Sequence types (STs), and clonal complexes (CCs) were assigned and the phylogenetic relationship was also evaluated. Thus, a total of 19 STs and 4 CCs were studied. Following the molecular analysis, six isolates of U. diversum were selected, inoculated into bovine monocyte/macrophage culture and evaluated for gene expression of the cytokines TNF-α, IL-1, IL-6, IL-10 and IL-17. Differences were detected in the induction of cytokines, especially between isolates 198 and BA78, promoted inflammatory and anti-inflammatory profiles, respectively, and they also differed in virulence factors.

Conclusion

It was observed that intra-species variability between isolates of U. diversum can induce variations of virulent determinants and, consequently, modulate the expression of the triggered immune response.
Validation of genome-wide association study-identified single nucleotide polymorphisms in a case-control study of pancreatic cancer from Taiwan
Authors: Shan Yan-Shen , Chen Li-Tzong , Wu Jin-Shang , Chang Yin-Fan , Lee Chih-Ting , Wu Chih-Hsing , Chiang Nai-Jung , Huang Hsin-En , Yen Chia-Jui , Chao Ying-Jui , Tsai Hui-Jen , Chen Chiung-Yu , Kang Jui-Wen , Kuo Chin-Fu , Tsai Chia-Rung , Weng Ya-Ling , Yang Han-Chien , Liu Hui-Chin , Chang Jeffrey S.
Published: May 2020

Background

Due to differences in genetic background, it is unclear whether the genetic loci identified by the previous genome-wide association studies (GWAS) of pancreatic cancer also play significant roles in the development of pancreatic cancer among the Taiwanese population.

Methods

This study aimed to validate the 25 pancreatic cancer GWAS-identified single nucleotide polymorphisms (SNPs) in a case-control study (278 cases and 658 controls) of pancreatic cancer conducted in Taiwan. Statistical analyses were conducted to determine the associations between the GWAS-identified SNPs and pancreatic cancer risk. Gene-environment interaction analysis was conducted to evaluate the interactions between SNPs and environmental factors on pancreatic cancer risk.

Results

Among the 25 GWAS-identified SNPs, 7 (rs2816938 (~ 11 kb upstream ofNR5A2), rs10094872 (~ 28 kb upstream ofMYC), rs9581943 (200 bp upstream ofPDX1) and 4 chromosome 13q22.1 SNPs: rs4885093, rs9573163, rs9543325, rs9573166) showed a statistically significant association with pancreatic cancer risk in the current study. Additional analyses showed two significant gene-environment interactions (between poor oral hygiene andNR5A2rs2816938 and between obesity andPDX1rs9581943) on the risk of pancreatic cancer.

Conclusions

The current study confirmed the associations between 7 of the 25 GWAS-identified SNPs and pancreatic risk among the Taiwanese population.

Furthermore, pancreatic cancer was jointly influenced by lifestyle and medical factors, genetic polymorphisms, and gene-environment interaction. Additional GWAS is needed to determine the genetic polymorphisms that are more relevant to the pancreatic cancer cases occurring in Taiwan.
Nanos3, a cancer-germline gene, promotes cell proliferation, migration, chemoresistance, and invasion of human glioblastoma
Authors: Zhang Fengyu , Liu Ruilai , Liu Cheng , Zhang Haishi , Lu Yuan
Published: May 2020

Background

Radiotherapy, chemotherapy, and surgery have made crucial strides in glioblastoma treatment, yet they often fail; thus, new treatment and new detection methods are needed. Aberrant expression of Nanos3 has been functionally associated with various cancers. Here, we sought to identify the clinical significance and potential mechanisms of Nanos3 in human glioblastoma.

Methods

Nanos3 expression was studied in nude mouse glioblastoma tissues and glioblastoma cell lines by immunohistochemistry, Western blot, and RT-PCR. Clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 gene editing assay was performed to generate the Nanos3 knockdown glioblastoma cell lines. The effects of Nanos3 on glioblastoma cells proliferation, migration, invasion, chemoresistance, germ cell characteristics, and tumor formation were analyzed by CCK8, transwell, cell survival experiments and alkaline phosphatase staining in vitro and in nude mouse models in vivo. Correlation between the expression of stemness proteins and the expression of Nanos3 was evaluated by Western blot.

Results

We found that Nanos3 was strongly expressed in both glioblastoma cell lines and tissues. Western blot and sequencing assays showed that the Nanos3 knockdown glioblastoma cell lines were established successfully, and we discovered that Nanos3 deletion reduced the proliferation, migration, and invasion of glioblastoma cells in vitro (P < 0.05). Nanos3 knockdown enhanced the sensitivity of glioblastoma cells to doxorubicin (DOX) and temozolomide (TMZ) (P < 0.05), and Nanos3+/− glioblastoma cell lines did not show the characteristics of the germline cells. In addition, Nanos3 deletion inhibited subcutaneous xenograft tumor growth in vivo (P < 0.001). Moreover, the oncogenesis germline protein levels of CD133, Oct4, Ki67, and Dazl decreased significantly in glioblastoma cells following Nanos3 knockdown.

Conclusions

Both in vitro and in vivo assays suggest that Nanos3, which is a cancer-germline gene, initiates the tumorigenesis of glioblastoma via acquiring the oncogenesis germline traits. These data demonstrate that ectopic germline traits are necessary for glioblastoma growth.
The differences in self-perceptions of aging, health-related quality of life and their association between urban and rural Chinese older hypertensive patients
Authors: Hou Yunying , Wu Qing , Zhang Dandan , Jin Xiaohong , Wu Wenya , Wang Xiaohua
Published: May 2020

Background

Most hypertensive clients are elderly, whose health-related quality of life (HRQL) may be associated with self-perceptions of aging (older individuals’ beliefs about their own aging). Meanwhile, culture and health disparities between rural and urban populations are substantial. Whether there are differences in self-perceptions of aging, HRQL, and their association among elderly hypertensive clients in urban and rural areas remains unknown. The objective of this study was to investigate and compare self-perceptions of aging and HRQL and their association among urban and rural older Chinese hypertensive clients.

Methods

A cross-sectional investigation was conducted in 15 urban community clinics and 22 village clinics from Suzhou, China. Older hypertensive adults were invited to complete a self-administered questionnaire addressing socio-demographic and clinical information, HRQL and self-perceptions of aging.

Results

There were 492 urban participants and 537 rural participants included in the analyses. The physical (40.0 ± 12.1 vs. 30.9 ± 8.9, P <  0.001) and mental (51.5 ± 8.3 vs. 46.0 ± 7.8, P <  0.001) HRQL scores of urban participants were all higher than those of rural ones. Urban participants’ scores on dimensions of “timeline cyclical”, “consequences negative”, and “control negative” of self-perceptions of aging questionnaire (APQ) were lower than those of rural participants (P <  0.001, respectively), while the scores on dimensions of “consequences positive” and “control positive” were higher (P <  0.001, respectively). Adjusted multivariate linear regression showed that participants who had worse self-perceptions of aging had poorer HRQL. Some APQ dimensions associated with urban or rural hypertensive elders’ HRQL were different.

Conclusions

Older hypertensive clients in rural areas have poorer self-perceptions of aging and HRQL than those in urban areas. Health care professionals should pay more attention to HRQL and self-perceptions of aging of older hypertensive clients in rural areas.
Preoperative squamous cell carcinoma antigen and albumin serum levels predict the survival of patients with stage T1-3N0M0 esophageal squamous cell carcinoma: a retrospective observational study
Authors: Wu Lei-Lei , Liu Xuan , Huang Wei , Lin Peng , Long Hao , Zhang Lan-Jun , Ma Guo-Wei
Published: May 2020

Background

This study aimed to explore the significance of preoperative levels of squamous cell carcinoma antigen (SCC-Ag) and albumin on the cancer-specific survival (CSS) of patients with stage T1-3N0M0 in esophageal squamous cell cancer (ESCC).

Methods

The data of 308 patients who underwent esophagectomy between 1996 and 2011 were analyzed. SCC-Ag and albumin levels were measure 1 week before surgery. The optimal cutoff levels of SCC-Ag and albumin were determined using the X-Tile software, which were 1.0 μg/L and 39.8 g/L, respectively. The associations between SCC-Ag and albumin levels and clinicopathological characteristics were assessed using the χ2 test, Student’s t-test and Fisher’s exact test. Cox univariable and multivariable analyses were computed to identify SCC-Ag and albumin levels as independent prognostic factors related to the CSS of patients with ESCC. We used the Kaplan-Meier survival curve to determine the significance of SCC-Ag and albumin level on ESCC in the long-term follow-up.

Results

The 5-year CSS rate for the entire cohort was 65.0%. There was a significant difference in CSS between the low and high SCC-Ag level groups (hazard ratio [HR], 1.828, 95% confidence interval [CI], 1.203–2.778; P = 0.005). Patients with ESCC with low albumin level had a worse CSS than those with high albumin level (HR, 0.540; 95% CI, 0.348–0.838; P = 0.006). Patients with both high SCC-Ag and low albumin levels had worse 5-year CSS than patients with low SCC-Ag and high albumin levels (P < 0.05).

Conclusions

Preoperative serum SCC-Ag and albumin levels can predict survival in patients ESCC with stage T1-3N0M0. Patients with ESCC with high SCC-Ag and low albumin levels may have a poor survival outcome.
TRUST4RD: tool for reducing uncertainties in the evidence generation for specialised treatments for rare diseases
Authors: Annemans Lieven , Makady Amr
Published: May 2020

Background

Many treatments developed for rare diseases will have an Orphan Medicinal Product (OMP) designation, indicating that they are likely to deliver benefit in an area of high unmet need. Their approval may be based on a small or uncontrolled trial, as randomised controlled trials (RCTs) of sufficient size are often difficult to conduct, or repeat, as a result of the rarity of the condition, sparsity of patients, or for ethical reasons. Furthermore, many products are given a conditional marketing authorisation, requiring additional evidence to be collected after product launch. This is even more challenging with the advent of advanced therapeutic medicinal products, which use novel scientific approaches like gene or somatic cell therapy.

Issue

Given the high unmet need associated with these products, there is pressure for Health Technology Assessment (HTA)/reimbursement bodies to enable rapid access to effective treatments. However, there is often only limited evidence available for assessment.

Methods

TRUST4RD proposes an approach to identify uncertainties of most concern for decision-makers by developing an iterative and informed dialogue amongst stakeholders (including manufacturers, clinicians, patients, regulatory- and HTA agencies and payers), so that potential approaches to resolution can be discussed. As evidence is generated, uncertainties are reviewed and prioritised, and evidence-generation plans revised or clarified accordingly. The aim is to develop – both pre- and post HTA submission – a better understanding of evidence requirements versus evidence-generation trade-offs as an evidence base grows and the potential value of a product becomes clearer.

Conclusion

TRUST4RD presents guidance on defining uncertainties and evidence gaps in the assessment of value and value for money of specialised treatments for rare diseases. It also provides guidance on the potential of Real World Evidence (RWE) to help address such uncertainties, including the typology of evidence uncertainties, the importance of different uncertainties and the data sources available to address them before and after HTA submission. In making use of the guidance, authorisation and reimbursement discussions on such treatments can be embedded in an evidence-rich context, thereby ensuring value to all parties, particularly to patients.
Surgical management of sarcoma in adolescent and young adult patients
Authors: Hashimoto Kazuhiko , Nishimura Shunji , Oka Naohiro , Akagi Masao
Published: May 2020

Objective

To examine the clinical features and outcomes of adolescent and young adult sarcoma patients who underwent surgical management and clarify important factors associated with prognosis. We reviewed 18 young adult sarcoma patients sarcoma patients treated surgically in our hospital. The tumor site, histology, grade, stage, and American Society of Anesthesiologists-Physical Status before surgery, operation time, intraoperative blood loss, complications, surgical margin, local recurrence, metastasis, and outcomes were investigated. The 3-year survival rate was also calculated. We compared survival based on age, grade, and surveyed features of poor outcome cases.

Results

The 3-year survival rate was 61.3%. There was no significant difference in survival based on age, grade, operation time, or intraoperative blood loss. Three of five patients who died of the disease had stage ≥ IV at diagnosis. All patients with R1 surgical margins developed recurrence and all those with an American Society of Anesthesiologists-Physical Status ≥ 2 died. Patients with late-stage sarcomas, R1 tumor margin, or high American Society of Anesthesiologists-Physical Status score had poor prognoses. To achieve a favorable outcome in adolescent and young adult sarcoma patients, early detection and obtaining R0 ≥ surgical margin are essential.
Hepatitis C virus relapse after successful treatment with direct-acting antivirals, followed by sarcomatous changes in hepatocellular carcinoma: a case report
Authors: Kurokawa Ken , Ohki Takamasa , Kato Jun , Fukumura Yukiyo , Imai Makoto , Shibata Chikako , Arai Junya , Kondo Mayuko , Takagi Kaoru , Kojima Kentaro , Seki Michiharu , Mori Masaya , Toda Nobuo , Tagawa Kazumi
Published: May 2020

Background

Combination therapy of interferon and ribavirin has traditionally been used to eradicate hepatitis C virus. The sustained virologic response achieved with interferon-related therapy is persistent, and late relapses after achieving sustained virologic response at 24 weeks using this therapy are reportedly rare (< 1%). In 2014, interferon-free therapy with direct-acting antivirals was developed, and the rate of sustained virologic response was improved. However, the persistence thereof remains uncertain, and the appropriate follow-up period for hepatitis C virus-positive patients is under discussion.

Case presentation

A 74-year-old Japanese man who had hepatitis C virus–related hepatocellular carcinoma and was successfully treated with radiofrequency ablation four times underwent direct-acting antiviral therapy with daclatasvir and asunaprevir; sustained virologic response at 24 weeks was confirmed. However, although he had no high risk factors for reinfection, hepatitis C virus ribonucleic acid was detected again 6 months after achieving sustained virologic response at 24 weeks. Moreover, he developed active hepatitis with an increased viral load. Five months after development of hepatitis, recurrent hepatocellular carcinoma emerged in segment II, where we had performed radiofrequency ablation 17 months previously. The recurrent hepatocellular carcinoma enlarged quite rapidly and induced multiple peritoneal disseminations and lung metastases. He died 3 months after the abrupt recurrence. A sarcomatous change in the hepatocellular carcinoma was identified during the autopsy.

Conclusions

Although sustained virologic response at 24 weeks has generally been regarded to denote complete eradication of hepatitis C virus, we present a patient in whom hepatitis C virus recurred 6 months after achieving sustained virologic response at 24 weeks with direct-acting antiviral therapy. In addition, a sarcomatous change in hepatocellular carcinoma emerged 5 months after active hepatitis developed due to late hepatitis C virus relapse in this case. The sarcomatous change in hepatocellular carcinoma is generally thought to be related to anticancer therapies, such as radiofrequency ablation. However, in this case, late viral relapse and active hepatitis in addition to the previous radiofrequency ablation could have been the trigger. There may be a need for follow-up of hepatitis C virus ribonucleic acid beyond sustained virologic response at 24 weeks with direct-acting antiviral therapy, owing to the possibility of late viral relapse and tumorigenesis.
Co-transplantation with adipose-derived cells to improve parathyroid transplantation in a mice model
Authors: Cui Qiuxia , Zhang Dan , Kong Deguang , Tang Jianing , Liao Xing , Yang Qian , Ren Jiangbo , Gong Yan , Wu Gaosong
Published: May 2020

Background

Accidentally removed parathyroid glands are still challenging in neck surgery, leading to hypoparathyroidism characterized with abnormally low levels of parathyroid hormone. Parathyroid auto-transplantation is usually applied in compensation. To improve the efficiency of parathyroid transplantation, we introduced a method by co-transplanting with adipose-derived cells, including stromal vascular fractions (SVFs) and adipose-derived stem cells (ADSCs), and investigated the underlying molecular mechanisms involved in parathyroid transplantation survival.

Methods

Rat and human parathyroid tissues were transplanted into nude mice as parathyroid transplantation model to examine the effects of SVFs and ADSCs on grafts angiogenesis and survival rates, including blood vessel assembly and parathyroid hormone levels. Several angiogenic factors, such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factor (FGF) 2, were assessed in parathyroid grafts. The effects of hypoxia were investigated on ADSCs. The modulatory roles of the eyes absent homolog 1 (EYA1), which is vital in parathyroid development, was also investigated on angiogenic factor production and secretion by ADSCs. All experimental data were statistically processed. Student’s t test was used to assess significant differences between 2 groups. For multiple comparisons with additional interventions, two-way ANOVA followed by Tukey’s post hoc test was performed. P < 0.05 was considered as significant.

Results

SVFs improve rat parathyroid transplantation survival and blood vessel assembly, as well as FGF2 and VEGF-A expression levels in parathyroid transplantation mice. Functional human parathyroid grafts have higher microvessel density and increased VEGF-A expression. The supernatant of ADSCs induced tubule formation and migration of human endothelial cells in vitro. Hypoxia had no effect on proliferation and apoptosis of human ADSCs but induced higher angiogenic factor levels of VEGF-A and FGF2, modulated by EYA1, which was confirmed by parathyroid glands transplantation in mice.

Conclusions

Adipose-derived cells, including ADSCs and SVFs, improve parathyroid transplantation survival via promoting angiogenesis through EYA1-regulating angiogenetic factors in vitro and in vivo. Our studies proved an effective method to improve the parathyroid autotransplantation, which is promising for clinical patients with hypoparathyroidism when parathyroid glands were accidentally injured, removed, or devascularized.
IoT cyber risk: a holistic analysis of cyber risk assessment frameworks, risk vectors, and risk ranking process
Authors: Kandasamy Kamalanathan , Srinivas Sethuraman , Achuthan Krishnashree , Rangan Venkat P.
Published: May 2020

Security vulnerabilities of the modern Internet of Things (IoT) systems are unique, mainly due to the complexity and heterogeneity of the technology and data. The risks born out of these IoT systems cannot easily fit into an existing risk framework. There are many cybersecurity risk assessment approaches and frameworks that are under deployment in many governmental and commercial organizations. Extending these existing frameworks to IoT systems alone will not address the new risks that have arisen in the IoT ecosystem. This study has included a review of existing popular cyber risk assessment methodologies and their suitability to IoT systems. National Institute of Standards and Technology, Operationally Critical Threat, Asset, and Vulnerability Evaluation, Threat Assessment & Remediation Analysis, and International Standards Organization are the four main frameworks critically analyzed in this research study. IoT risks are presented and reviewed in terms of the IoT risk category and impacted industries. IoT systems in financial technology and healthcare are dealt with in detail, given their high-risk exposure. Risk vectors for IoT and the Internet of Medical Things (IoMT) are discussed in this study. A unique risk ranking method to rank and quantify IoT risk is introduced in this study. This ranking method initiates a risk assessment approach exclusively for IoT systems by quantifying IoT risk vectors, leading to effective risk mitigation strategies and techniques. A unique computational approach to calculate the cyber risk for IoT systems with IoT-specific impact factors has been designed and explained in the context of IoMT systems.
Locating unregistered and unreported data for use in a social science systematic review and meta-analysis
Authors: Polanin Joshua R. , Espelage Dorothy L. , Grotpeter Jennifer K. , Valido Alberto , Ingram Katherine M. , Torgal Cagil , El Sheikh America , Robinson Luz E.
Published: May 2020

Meta-analysts rely on the availability of data from previously conducted studies. That is, they rely on primary study authors to register their outcome data, either in a study’s text or on publicly available websites, and report the results of their work, either again in a study’s text or on publicly accessible data repositories. If a primary study author does not register data collection and similarly does not report the data collection results, the meta-analyst is at risk of failing to include the collected data. The purpose of this study is to attempt to locate one type of meta-analytic data: findings from studies that neither registered nor reported the collected outcome data. To do so, we conducted a large-scale search for potential studies and emailed an author query request to more than 600 primary study authors to ask if they had collected eligible outcome data. We received responses from 75 authors (12.3%), three of whom sent eligible findings. The results of our search confirmed our proof of concept (i.e., that authors collect data but fail to register or report it publicly), and the meta-analytic results indicated that excluding the identified studies would change some of our substantive conclusions. Cost analyses indicated, however, a high price to finding the missing studies. We end by reaffirming our calls for greater adoption of primary study pre-registration as well as data archiving in publicly available repositories.
A case of triple digestive tract reconstruction in chronic pancreatitis complicated with bile ductal stenosis, duodenal stenosis, and portal vein stenosis: a case report
Authors: Abe Yuka , Kumamoto Takafumi , Nakayama Gakuryu , Miyake Kentaro , Yabushita Yasuhiro , Sawada Yu , Homma Yuki , Takeda Kazuhisa , Matsuyama Ryusei , Endo Itaru
Published: May 2020

Background

Although endoscopic interventions for chronic pancreatitis are highly developed, surgery for severe complicated cases such as the coexistence of bile duct, duodenum, and portal vein stenosis is a challenging issue for surgeons. In such instances, pancreaticoduodenectomy could lead to massive intraoperative bleeding due to severe collateral veins. A surgical drainage procedure, instead of pancreatic resection, may be a reasonable and safer option in such cases, but the literature on a surgical drainage technique to resolve all obstructions of the pancreatic duct, bile duct, and duodenum at once is limited. We devised a new surgical drainage method for such cases with consideration for a possible future second surgery for newly developed pancreatic cancer because chronic pancreatitis is a well-known high-risk factor for pancreatic cancer in the long term. Here, we report this surgical procedure.

Case presentation

A 55-year-old man was diagnosed with alcoholic chronic pancreatitis 15 years ago. Before surgery, he underwent regular endoscopic pancreatic stenting for pancreatic ductal stenosis for 3 years. Three months before surgery, his duodenal stenosis worsened, and he was referred to our department for surgery. Preoperative imaging revealed pancreatic and bile duct stenosis, duodenal stenosis, and portal vein stenosis. To avoid intraoperative bleeding caused by the development of collateral veins, we performed a triple drainage procedure: longitudinal pancreaticojejunostomy with coring-out of the pancreatic head, hepaticojejunostomy, and gastrojejunostomy. The patient did not develop postoperative complications, and he was discharged from the hospital on postoperative day 14. For 5 years after surgery, no abdominal pain or recurrent pancreatitis was observed.

Conclusion

Our triple drainage procedure seems effective and minimally invasive for patients complicated with bile duct stenosis, duodenal stenosis, and portal vein stenosis.
Small bowel stenosis after blunt abdominal trauma: a case report
Authors: Hara Kazushi , Yamamoto Manabu , Sakamoto Teruhisa , Sugezawa Ken , Uejima Chihiro , Tanio Akimitsu , Tada Yoichiro , Hanaki Takehiko , Miyatani Kozo , Watanabe Joji , Kihara Kyoichi , Tokuyasu Naruo , Takano Shuichi , Honjo Soichiro , Fujiwara Yoshiyuki
Published: May 2020

Background

Small bowel stenosis after blunt abdominal trauma is relatively rare, and progression from trauma to bowel stenosis might sometimes be delayed. Herein, we report the case of a patient who was diagnosed with small bowel stenosis relatively early and received laparoscopic surgery.

Case presentation

An 18-year-old Japanese male was in a traffic accident and was urgently transported to our hospital. On arrival, he was admitted with right kidney and right adrenal injury and abdominal aortic aneurysm. On hospital day 13, he vomited during conservative treatment without surgery, and computed tomography revealed small bowel stenosis and dilatation of the oral-side small bowel. No improvement with the ileus tube occurred, and he received laparoscopic surgery on hospital day 21. Briefly, the abdominal cavity was observed with a laparoscope. The mesentery was congested, scarring around the stenotic small bowel regions was present, and three stenotic regions were observed 40–50 cm from the Treitz ligament. The patient received partial resection and anastomosis of the small bowel. The postoperative course was stable, and he was discharged on postoperative day eight.

Conclusions

Most cases of bowel stenosis after abdominal trauma are irreversible and usually require surgical treatment. Therefore, small bowel stenosis should be considered in patients with abdominal symptoms after blunt abdominal trauma.
Determining the effectiveness of fibrin sealants in reducing complications in patients undergoing lateral neck dissection (DEFeND): study protocol for a randomised external pilot trial
Authors: Bajwa Mandeep S. , Carruthers Stacey , Hanson Rob , Jackson Richard , Braithwaite Chris , Edwards Mike , Chauhan Seema , Smith Catrin Tudur , Shaw Richard J. , Schache Andrew G.
Published: May 2020

Background

Complications after major surgery are a significant cause of morbidity and mortality. Neck dissection is one of the most commonly performed major operations in Head and Neck Surgical Oncology. Significant surgical complications occur in approximately 10–20% of all patients, increasing to 40% in patients who have had previous treatment to the area or have multiple co-morbidities and/or polypharmacy.

Current evidence suggests that fibrin sealants (FS) may have potential clinical advantages in Head and Neck Surgery through the reduction of complications, volume of wound drainage and retention time of the drains. However, a paucity of high-quality trial-based evidence means that a surgical trial to determine the effectiveness of FS in reducing the rate and severity of complications in patients undergoing lateral neck dissection is warranted. The DEFeND randomised external pilot trial will address critical questions on how well key components of the proposed study design work together as well as the feasibility of a future phase III trial.

Methods

The study design that is being piloted is that of a two-arm, parallel group, superiority trial with block randomisation in a 1:1 allocation ratio. The interventional arm will constitute the application of FS (Artiss, Baxter Healthcare Ltd.) to the surgical wound following completion of a neck dissection procedure, in addition to standard of care (SOC). The control arm will constitute SOC alone. Eligible patients will include patients who require a lateral neck dissection with a minimum of three cervical nodal levels. Patients who require bilateral neck procedures or undergoing immediate reconstruction with free or regional flaps will be excluded. The outcomes being assessed will be recruitment rate, screened to randomisation rate, fidelity of blinding process using blinding indices, number of missing or incomplete data entries, number of protocol deviations and number of losses to follow-up. Suitability of the outcome measures proposed for the future phase III trial will also be assessed.

Discussion

The anticipated challenges for this study will be recruitment, complexity of the intervention and adherence to the protocol. The outcomes will inform the design, feasibility and conduct of a future phase III surgical trial.

Trial registration

First participant randomised: November 06, 2018; UKCRN Portfolio ID: 37896; ISRCTN99181100.