scholarly journals Development, validation, and implementation of biomarker testing in cardiovascular medicine state-of-the-art: proceedings of the European Society of Cardiology—Cardiovascular Round Table

2020 ◽  
Author(s):  
Perry Elliott ◽  
Martin R Cowie ◽  
Jennifer Franke ◽  
André Ziegler ◽  
Charalambos Antoniades ◽  
...  
Keyword(s):  
Clinical Practice ◽  
New Technologies ◽  
Biomarker Discovery ◽  
Real Life ◽  
High Sensitivity ◽  
Standard Of Care ◽  
Round Table ◽  
Current Standard ◽  
Development Pathway ◽  
Regulatory Standards

Abstract Many biomarkers that could be used to assess ejection fraction, heart failure, or myocardial infarction fail to translate into clinical practice because they lack essential performance characteristics or fail to meet regulatory standards for approval. Despite their potential, new technologies have added to the complexities of successful translation into clinical practice. Biomarker discovery and implementation require a standardized approach that includes: identification of a clinical need; identification of a valid surrogate biomarker; stepwise assay refinement, demonstration of superiority over current standard-of-care; development and understanding of a clinical pathway; and demonstration of real-world performance. Successful biomarkers should improve efficacy or safety of treatment, while being practical at a realistic cost. Everyone involved in cardiovascular healthcare, including researchers, clinicians, and industry partners, are important stakeholders in facilitating the development and implementation of biomarkers. This article provides suggestions for a development pathway for new biomarkers, discusses regulatory issues and challenges, and suggestions for accelerating the pathway to improve patient outcomes. Real-life examples of successful biomarkers—high-sensitivity cardiac troponin, T2* cardiovascular magnetic resonance imaging, and echocardiography—are used to illustrate the value of a standardized development pathway in the translation of concepts into routine clinical practice.

scholarly journals A Streamlined Approach to Prader-Willi and Angelman Syndrome Molecular Diagnostics

2021 ◽  
Vol 12 ◽  
Author(s):  
Samuel P. Strom ◽  
Waheeda A. Hossain ◽  
Melina Grigorian ◽  
Mickey Li ◽  
Joseph Fierro ◽  
...  
Keyword(s):  
Angelman Syndrome ◽  
Genetic Defect ◽  
Point Mutations ◽  
High Sensitivity ◽  
Standard Of Care ◽  
Disease Diagnosis ◽  
Genetic Alterations ◽  
Chromosome 15 ◽  
Current Standard ◽  
Care Technology

Establishing or ruling out a molecular diagnosis of Prader–Willi or Angelman syndrome (PWS/AS) presents unique challenges due to the variety of different genetic alterations that can lead to these conditions. Point mutations, copy number changes, uniparental isodisomy (i-UPD) 15 of two subclasses (segmental or total isodisomy), uniparental heterodisomy (h-UPD), and defects in the chromosome 15 imprinting center can all cause PWS/AS. Here, we outline a combined approach using whole-exome sequencing (WES) and DNA methylation data with methylation-sensitive multiplex ligation-dependent probe amplification (MLPA) to establish both the disease diagnosis and the mechanism of disease with high sensitivity using current standard of care technology and improved efficiency compared to serial methods. The authors encourage the use of this approach in the clinical setting to confirm and establish the diagnosis and genetic defect which may account for the secondary genetic conditions that may be seen in those with isodisomy 15, impacting surveillance and counseling with more accurate recurrence risks. Other similarly affected individuals due to other gene disorders or cytogenetic anomalies such as Rett syndrome or microdeletions would also be identified with this streamlined approach.

scholarly journals A porcine bimicrobial abscess model for testing interventional treatments

2020 ◽  
Author(s):  
Yak-Nam Wang ◽  
Andrew A. Brayman ◽  
Keith T. Chan ◽  
Keith Richmond ◽  
Wayne L. Monsky ◽  
...  
Keyword(s):  
Animal Model ◽  
New Technologies ◽  
Defense Mechanism ◽  
Trauma Surgery ◽  
Standard Of Care ◽  
The Body ◽  
Large Animal Model ◽  
Histological Evaluation ◽  
Large Animal ◽  
Current Standard

AbstractBackgroundAbscess formation is a host defense mechanism to contain the spread of infection. Abscesses can affect any part of the body and are common sequelae to complications of trauma, surgery, systemic infections and other disease states. Most models for abscesses are in small animals. Pursuant to the goal of developing more advanced treatments for abscesses, we sought to develop a large animal model which would reasonably mimic a fluid-filled human abscess.MethodsDomestic swine were inoculated with a bimicrobial mixture of Bacteroides fragilis (B. fragilis) and Escherichia coli (E. coli) supplemented with an irritant (dextran). Inoculations were performed under ultrasound guidance in the muscle, subcutaneously or intradermally within the same animal. Fourteen days after inoculation, lesions were imaged with ultrasound, resected and prepared for histological evaluation.ResultsInjection of bimicrobial (aerobic and anaerobic) bacterial mixtures at multiple sites in a pig produced multiple lesions with histological features similar to encapsulated and multiloculated/multichamber abscesses often observed clinically in humans. Important salient features include the formation of a connective tissue capsule surrounding histologically nearly amorphous pus.ConclusionsThis paper provides the first description of a pig model for multiloculated abscesses. This animal model could potentially enable the evaluation of new technologies to replace or augment the current standard of care (image-guided percutaneous abscess drainage with antibiotics).

Participatory Design in Health Research: A Way to Change Clinical Practice (Preprint)

2021 ◽  
Author(s):  
Jane Clemensen ◽  
Kristina Garne Holm ◽  
Pernille Ravn Jakobsen ◽  
Charlotte Myhre Jensen ◽  
Charlotte Nielsen ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Health Research ◽  
Participatory Design ◽  
New Technologies ◽  
Real Life ◽  
User Participation ◽  
Health Science ◽  
Organizational Changes ◽  
Health Technologies ◽  
Patient Pathways

BACKGROUND Participatory Design (PD) is a methodology that focuses on user participation in the design of new technologies to leverage organizational changes. PD emerged within the computer field in the 1970s and 1980s when new programs and technologies were developed to empower workers by involving them in matters that concerned them. The concept of ‘users’ emerged during the design and development of personal computers. Consequently, users became central and key decision-makers in the generation of new technology. PD in health research has been proven to change clinical practice. Genuine user involvement that includes all stakeholders, and robust collaborations across sciences, sectors, and disciplines are basic elements of successful research to change clinical practice and to implement novel technical and organizational approaches. OBJECTIVE The aim of this paper is to share knowledge, experiences, and reflections regarding the results and impact of 7 studies completed by our group by: • Describing how PD can be applied in health science. • Illustrating how PD facilitates organizational changes, new perspectives and new communication methods. • Explaining the relevance and suitability of PD as a research design in health science. • Providing recommendations for conducting PD studies in health research. METHODS We reviewed 7 PD-based health science research studies which our group completed over a 19-year span. The paper presents examples from the 3 phases of PD and finally offers recommendations for future PD researchers. RESULTS This paper presents examples from 7 PD studies and finally offers recommendations for future PD researchers. All of the described studies promoted organizational changes supported by health technology and have been implemented at either international, national, regional, or local levels. In all the studies the researcher supported and facilitated creative processes in which users were heard and could participate when aiming to change clinical practice supported by new health technologies or novel applications of extant technology developed in close collaboration. An important component of all the PD studies was the field study as an ideal method to observe needs and interventions in real-life settings. CONCLUSIONS The use of PD in clinical health research facilitates new ways of offering patient pathways supported by tailored technology. In PD mutual learning and co-creation is facilitated. Thus, learning from users, rather than studying them, corroborates extant information and reveals new knowledge.

scholarly journals Effectiveness and toxicity of lenvatinib in refractory thyroid cancer: Dutch real-life data

2020 ◽  
Vol 182 (2) ◽  
pp. 131-138 ◽  
Author(s):  
M D Aydemirli ◽  
E Kapiteijn ◽  
K R M Ferrier ◽  
P B Ottevanger ◽  
T P Links ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Clinical Practice ◽  
Gallbladder Disease ◽  
Real Life ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Patient Characteristics ◽  
Eligibility Criteria ◽  
Real Life Situation ◽  
Select Trial

Objective The SELECT trial showed progression-free survival (PFS) benefit for lenvatinib for advanced radioiodine-refractory differentiated thyroid cancer (RAI-refractory or RR-DTC) patients, on which current clinical practice is based. We assessed whether the effectiveness and toxicity of lenvatinib in real-life clinical practice in the Netherlands were comparable to the pivotal SELECT trial. Methods From three Dutch centres Electronic Health Records (EHRs) of patients treated in the lenvatinib compassionate use program or as standard of care were reviewed and checked for SELECT eligibility criteria. Baseline characteristics, safety, and efficacy measures were compared and PFS and overall survival (OS) were calculated. Furthermore, PFS was compared to estimates of PFS reported in other studies. Results A total of 39 DTC patients with a median age of 62 years were analysed. Of these, 27 patients (69%) did not fulfil the SELECT eligibility criteria. The most common grade ≥3 toxicities were hypertension (n = 11, 28%), diarrhoea (n = 7, 18%), vomiting (n = 4, 10%), and gallbladder disease (n = 3, 8%). Median PFS and median OS were 9.7 (95% confidence interval (CI): 4.0–15.5) and 18.3 (95% CI: 4.9–31.7) months, respectively, response rate was 38% (95% CI: 23–54%). PFS in the Dutch real-life situation was comparable to previous real-life studies, but inferior to PFS as shown in the SELECT trial (P = 0.04). Conclusions PFS in our non-trial population was significantly shorter than in the SELECT trial population. In the interpretation of results, differences in the real-life population and the SELECT study population regarding patient characteristics should be taken into account.

scholarly journals New Technologies for Sentinel Lymph Node Detection

Breast Care ◽  
2018 ◽  
Vol 13 (5) ◽  
pp. 349-353 ◽  
Author(s):  
Amit Goyal
Keyword(s):  
Sentinel Node ◽  
New Technologies ◽  
Superparamagnetic Iron Oxide ◽  
Standard Of Care ◽  
Alternative Methods ◽  
Blue Dye ◽  
Sentinel Node Mapping ◽  
Current Standard ◽  
Developed Country ◽  
Combination Technique

The ‘standard of care' method for sentinel node mapping is the combination technique using radioisotope and blue dye although some centres use radioisotope or blue dye alone. Radioisotope usage requires licensing, has regulatory issues around handling and disposal of waste, and logistically may be unavailable or difficult to implement in some centres or less developed country. This has led to the development of alternative methods such as superparamagnetic iron oxide (SPIO), fluorescence techniques using indocyanine green (ICG) or fluorescein, computed tomography lymphography, and contrast-enhanced ultrasound scan (CEUS) using microbubbles. The newer techniques will potentially enable a more widespread adoption of this procedure; however, a common barrier for these techniques is the lack of standardisation and no randomised trials to evaluate their effectiveness against the current standard of care. Furthermore, many of these techniques are more costly and may become redundant in node-negative patients with small tumours if ongoing trials show that sentinel node biopsy offers no additional benefit to grey-scale axillary ultrasound. This review discusses the new techniques for sentinel node mapping that have emerged including their pros and cons.

scholarly journals How I treat the young patient with multiple myeloma

Blood ◽  
2018 ◽  
Vol 132 (11) ◽  
pp. 1114-1124 ◽  
Author(s):  
Sara Gandolfi ◽  
Claudia Paba Prada ◽  
Paul G. Richardson
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Proteasome Inhibitors ◽  
High Sensitivity ◽  
Standard Of Care ◽  
Autologous Stem Cell Transplant ◽  
Novel Agents ◽  
Cell Transplant ◽  
Current Standard ◽  
Disease Biology

Abstract The treatment landscape for multiple myeloma has been transformed by the introduction of novel agents, including immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies. These have been shown to be more effective and generally better tolerated than conventional chemotherapy, with their introduction into clinical practice leading to improved survival. Furthermore, a better understanding of disease biology, improved diagnostic criteria, and the development of sensitive and specific tools for disease prognostication have contributed to better outcome. Treatment in the younger patient can now be individualized based on host and disease features with enhanced monitoring of response and use of high-sensitivity techniques for evaluating residual disease. The current standard of care has been significantly enhanced by novel agents with a paradigm shift toward optional or delayed autologous stem cell transplant as a reasonable choice in selected patients. Conversely, extended treatment with induction of remission followed by maintenance strategies is now a standard of care, conferring prolonged disease control with more manageable toxicities in both the short and long term, as well as improved quality of life.

scholarly journals COT-19 TREATMENT EXPERIENCE OF AND TIPS FOR ADMINISTRATING NOVO TTF

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii44-ii44
Author(s):  
Daisuke Shimada ◽  
Keiichi Kobayashi ◽  
Kuniaki Saito ◽  
Yoshie Matsumoto ◽  
Yoshiaki Shiokawa ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Newly Diagnosed ◽  
Current Standard ◽  
Free Survival ◽  
Tumor Treating Fields ◽  
Newly Diagnosed Glioblastoma ◽  
Medical Professions ◽  
Recommendation Grade

Abstract BACKGROUNDS Current standard of care for glioblastoma, consists of postoperative temozolomide (TMZ) concomitant with radiotherapy, followed by adjuvant TMZ monotherapy. Recently, an international phase 3 trial (EF-14) demonstrated that addition of tumor-treating fields (TTF) to adjuvant TMZ after completion of chemoradiotherapy extended median progression-free survival and overall survival by 2.7 months and 4.8 months, respectively, compared with TMZ alone in patients with newly diagnosed glioblastoma. TTF is now considered as a part of its initial treatment in the guideline in Japan (recommendation grade B). However,distinct from anticancer drugs,little is known or experienced using TTF as a therapeutic device so far, especially in management and handling. METHODS First six patients with newly diagnosed glioblastoma who underwent TTF were analyzed with special interest in medical and social supports to execute TTF at home. RESULTS TTF was first introduced in our institution in May 2016, but no patients were treated because of no coverage by medical insurance until December 2017. We further needed to wait to initiate TTF treatment until January 2019 when the contract to use TTF systems was finally made between the company and institution. Since then six patients were registered in five months. For its introduction to clinical practice,it is essential to establish new in-house environment with medical professions division in the facility including documentations of calculating instruction fees and usage guidance for home care application of TTF. It is also important to initiate providing information of TTF such as timing of visit by specific practitioners and potential medical and psychologic burdens to patients and their families during and after chemoradiotherapy to better understand this new modality leading to the consent acquisition. CONCLUSIONS Introducing TTF into clinical practice should accompany improvement of management in not only medical equipment and documentations but also patient care in hospital and home.

Acute Rejection Following Kidney Transplantation: State-of-the-Art and Future Perspectives

2020 ◽  
Vol 26 (28) ◽  
pp. 3468-3496
Author(s):  
Emilio Rodrigo ◽  
Marcio F. Chedid ◽  
David San Segundo ◽  
Juan C.R. San Millán ◽  
Marcos López-Hoyos
Keyword(s):  
Kidney Transplantation ◽  
Acute Rejection ◽  
Rescue Therapy ◽  
Standard Of Care ◽  
Rejection Rate ◽  
New Drugs ◽  
High Dose ◽  
Current Standard ◽  
Antibody Mediated Rejection ◽  
Cellular Rejection

: Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available metaanalyses, we performed a narrative review focused on the basic mechanisms and current and future therapies of acute rejection in kidney transplantation. : According to Kidney Disease/Improving Global Outcomes (KDIGO) guidelines, both clinical and subclinical acute rejection episodes should be treated. Usually, high dose steroids and basal immunosuppression optimization are the first line of therapy in treating acute cellular rejection. Rabbit antithymocytic polyclonal globulins are used as rescue therapy for recurrent or steroid-resistant cellular rejection episodes. Current standard-of-care (SOC) therapy for acute antibody-mediated rejection (AbMR) is the combination of plasma exchange with intravenous immunoglobulin (IVIG). Since a significant rate of AbMR does not respond to SOC, different studies have analyzed the role of new drugs such as Rituximab, Bortezomib, Eculizumab and C1 inhibitors. Lack of randomized controlled trials and heterogenicity among performed studies limit obtaining definite conclusions. Data about new direct and indirect B cell and plasma cell depleting agents, proximal and terminal complement blockers, IL-6/IL-6R pathway inhibitors and antibody removal agents, among other promising drugs, are reviewed.

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