Nanomedicine potential for endometriosis treatment

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Early Stage ◽  
Clinical Effectiveness ◽  
Medication Administration ◽  
Proof Of Concept ◽  
Depot Formulation ◽  
Medication Delivery ◽  
Vaginal Rings ◽  
Delivery Mechanism ◽  
Treatment Alternatives ◽  
Delivery Techniques

Contraception has previously provided alternative medication delivery techniques for the treatment of endometriosis. Only LNG-IUSs and depot formulation (DMPA), however, have been studied in numerous RCTs to treat patients. These approaches tend to enhance patient compliance and satisfaction when compared to other conventional treatment alternatives. Nanotechnologies are potential new drug delivery techniques that have been shown to deliver compounds with a particular therapeutic impact. However, the information is limited and preliminary. Endometriosis research has identified the patients who could benefit most from this kind of medication administration. No one has ever been used in a clinical study to treat endometria. Alternative medication delivery techniques may help to enhance compliance, effectiveness, and the development of novel treatment approaches. The use of vaginal rings as a unique and alternative medication delivery route for AIs, as well as the experience with danazol, are examples. The vaginal ring has been studied as a new medication delivery mechanism for danazol and aromatase inhibitors. Nanotechnologies are made up of bioconjugates that deliver anti-inflammatory, antioxidant, anti-angiogenic, and immunomodulating chemicals directly to the illness site. At this early stage of proof-of-concept, the evidence is limited and tentative. Clinical effectiveness can not be predicted using mouse models.

scholarly journals TOWARDS A VERIFICATION AND VALIDATING TESTING FRAMEWORK TO DEVELOP BESPOKE MEDICAL PRODUCTS IN RESEARCH-FUNDED PROJECTS

2021 ◽  
Vol 1 ◽  
pp. 3199-3208
Author(s):  
Emanuel Balzan ◽  
Pierre Vella ◽  
Philip Farrugia ◽  
Edward Abela ◽  
Glenn Cassar ◽  
...  
Keyword(s):  
Medical Devices ◽  
Early Stage ◽  
Design Stage ◽  
Concept Design ◽  
Proof Of Concept ◽  
Detailed Design ◽  
Testing Framework ◽  
Medical Products ◽  
Manufacturing Technologies ◽  
Validation Testing

AbstractResearch funded projects are often concerned with the development of proof-of-concept products. Consequently, activities related to verification and validation testing (VVT) are often not considered in depth, even though various design iterations are carried out to refine an idea. Furthermore, the introduction of additive manufacturing (AM) has facilitated, in particular, the development of bespoke medical products. End bespoke products, which will be used by relevant stakeholders (e.g. patients and clinicians) are fabricated with the same manufacturing technologies used during prototyping. As a result, the detailed design stage of products fabricated by AM is much shorter. Therefore, to improve the market-readiness of bespoke medical devices, testing must be integrated within the development from an early stage, allowing better planning of resources. To address these issues, in this paper, a comprehensive VVT framework is proposed for research projects, which lack a VVT infrastructure. The framework builds up on previous studies and methods utilised in industry to enable project key experts to capture risks as early as the concept design stage.

scholarly journals Skeletal muscle PGC-1β signaling is sufficient to drive an endurance exercise phenotype and to counteract components of detraining in mice

2017 ◽  
Vol 312 (5) ◽  
pp. E394-E406 ◽  
Author(s):  
Samuel Lee ◽  
Teresa C. Leone ◽  
Lisa Rogosa ◽  
John Rumsey ◽  
Julio Ayala ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Early Stage ◽  
Peroxisome Proliferator ◽  
Disuse Atrophy ◽  
Proof Of Concept ◽  
Peroxisome Proliferator Activated Receptor ◽  
Muscle Disuse ◽  
Training Response

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and -1β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise-training-detraining protocol. Second, using multiple physiological and gene expression end points, we found that PGC-1β overexpression in skeletal muscle of sedentary mice fully recapitulated the training response. Lastly, PGC-1β overexpression during the detraining period resulted in partial prevention of the detraining response. Specifically, an increase in the plateau at which O2 uptake (V̇o2) did not change from baseline with increasing treadmill speed [peak V̇o2 (ΔV̇o2max)] was maintained in trained mice with PGC-1β overexpression in muscle 6 wk after cessation of training. However, other detraining responses, including changes in running performance and in situ half relaxation time (a measure of contractility), were not affected by PGC-1β overexpression. We conclude that while activation of muscle PGC-1β is sufficient to drive the complete endurance phenotype in sedentary mice, it only partially prevents the detraining response following exercise training, suggesting that the process of endurance detraining involves mechanisms beyond the reversal of muscle autonomous mechanisms involved in endurance fitness. In addition, the protocol described here should be useful for assessing early-stage proof-of-concept interventions in preclinical models of muscle disuse atrophy.

scholarly journals What do Cochrane systematic reviews say about the clinical effectiveness of screening and diagnostic tests for cancer?

2017 ◽  
Vol 135 (4) ◽  
pp. 401-410 ◽  
Author(s):  
André Tito Pereira Bueno ◽  
Vladimir Lisboa Capelasso ◽  
Rafael Leite Pacheco ◽  
Carolina de Oliveira Cruz Latorraca ◽  
Tiago Biachi de Castria ◽  
...  
Keyword(s):  
Cancer Screening ◽  
Systematic Reviews ◽  
Cancer Mortality ◽  
Early Stage ◽  
Clinical Effectiveness ◽  
Adverse Outcomes ◽  
Screening Tests ◽  
Fecal Occult Blood ◽  
Clinical Effects ◽  
Cochrane Reviews

ABSTRACT CONTEXT AND OBJECTIVE: The purpose of screening tests for cancer is to detect it at an early stage in order to increase the chances of treatment. However, their unrestrained use may lead to unnecessary examinations, overdiagnosis and higher costs. It is thus necessary to evaluate their clinical effects in terms of benefits and harm. DESIGN AND SETTING: Review of Cochrane systematic reviews, carried out in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo. METHODS: Cochrane reviews on the clinical effectiveness of cancer screening procedures were included. Study titles and abstracts were independently assessed by two authors. Conflicts were resolved by another two authors. Findings were summarized and discussed. RESULTS: Seventeen reviews were selected: fifteen on screening for specific cancers (bladder, breast, colorectal, hepatic, lung, nasopharyngeal, esophageal, oral, prostate, testicular and uterine) and two others on cancer in general. The quality of evidence of the findings varied among the reviews. Only two reviews resulted in high-quality evidence: screening using low-dose computed tomography scans for high-risk individuals seems to reduce lung cancer mortality; and screening using flexible sigmoidoscopy and fecal occult blood tests seems to reduce colorectal cancer mortality. CONCLUSION: The evidence found through Cochrane reviews did not support most of the commonly used screening tests for cancer. It is recommended that patients should be informed of the possibilities of false positives and false negatives before they undergo the tests. Further studies to fully assess the effectiveness of cancer screening tests and adverse outcomes are required.

scholarly journals Digital Screening for Cognitive Impairment – A Proof of Concept Study

2021 ◽  
pp. 1-8
Author(s):  
V. Bloniecki ◽  
G. Hagman ◽  
M. Ryden ◽  
M. Kivipelto
Keyword(s):  
Cognitive Impairment ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Roc Curves ◽  
University Hospital ◽  
Cognitive Test ◽  
Test Time ◽  
Proof Of Concept ◽  
Cognitive Screening ◽  
Disease Modifying Drugs

Background: Due to an ageing demographic and rapid increase of cognitive impairment and dementia, combined with potential disease-modifying drugs and other interventions in the pipeline, there is a need for the development of accurate, accessible and efficient cognitive screening instruments, focused on early-stage detection of neurodegenerative disorders. Objective: In this proof of concept report, we examine the validity of a newly developed digital cognitive test, the Geras Solutions Cognitive Test (GCST) and compare its accuracy against the Montreal Cognitive Assessment (MoCA). Methods: 106 patients, referred to the memory clinic, Karolinska University Hospital, due to memory complaints were included. All patients were assessed for presence of neurodegenerative disorder in accordance with standard investigative procedures. 66% were diagnosed with subjective cognitive impairment (SCI), 25% with mild cognitive impairment (MCI) and 9% fulfilled criteria for dementia. All patients were administered both MoCA and GSCT. Descriptive statistics and specificity, sensitivity and ROC curves were established for both test. Results: Mean score differed significantly between all diagnostic subgroups for both GSCT and MoCA (p<0.05). GSCT total test time differed significantly between all diagnostic subgroups (p<0.05). Overall, MoCA showed a sensitivity of 0.88 and specificity of 0.54 at a cut-off of <=26 while GSCT displayed 0.91 and 0.55 in sensitivity and specificity respectively at a cut-off of <=45. Conclusion: This report suggests that GSCT is a viable cognitive screening instrument for both MCI and dementia.

The Impact of Delayed Symptomatic Treatment Implementation in the Intensive Care Unit

Healthcare ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 35
Author(s):  
Lesley Meng ◽  
Krzysztof Laudanski ◽  
Mariana Restrepo ◽  
Ann Huffenberger ◽  
Christian Terwiesch
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Medical Center ◽  
Academic Medical Center ◽  
Symptomatic Treatment ◽  
Medication Administration ◽  
Average Delay ◽  
Treatment Implementation ◽  
Medication Delivery ◽  
The Impact

We estimated the harm related to medication delivery delays across 12,474 medication administration instances in an intensive care unit using retrospective data in a large urban academic medical center between 2012 and 2015. We leveraged an instrumental variables (IV) approach that addresses unobserved confounds in this setting. We focused on nurse shift changes as disruptors of timely medication (vasodilators, antipyretics, and bronchodilators) delivery to estimate the impact of delay. The average delay around a nurse shift change was 60.8 min (p < 0.001) for antipyretics, 39.5 min (p < 0.001) for bronchodilators, and 57.1 min (p < 0.001) for vasodilators. This delay can increase the odds of developing a fever by 32.94%, tachypnea by 79.5%, and hypertension by 134%, respectively. Compared to estimates generated by a naïve regression approach, our IV estimates tend to be higher, suggesting the existence of a bias from providers prioritizing more critical patients.

scholarly journals Discovery of Prognostic Markers for Early-Stage High-Grade Serous Ovarian Cancer by Maldi-Imaging

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2000
Author(s):  
Hagen Kulbe ◽  
Oliver Klein ◽  
Zhiyang Wu ◽  
Eliane T. Taube ◽  
Wanja Kassuhn ◽  
...  
Keyword(s):  
Roc Analysis ◽  
Operating Characteristic ◽  
Prognostic Markers ◽  
Early Stage ◽  
Imaging Mass Spectrometry ◽  
Maldi Imaging ◽  
High Grade ◽  
Proof Of Concept ◽  
Tissue Sections ◽  
Maldi Ims

With regard to relapse and survival, early-stage high-grade serous ovarian (HGSOC) patients comprise a heterogeneous group and there is no clear consensus on first-line treatment. Currently, no prognostic markers are available for risk assessment by standard targeted immunohistochemistry and novel approaches are urgently required. Here, we applied MALDI-imaging mass spectrometry (MALDI-IMS), a new method to identify distinct mass profiles including protein signatures on paraffin-embedded tissue sections. In search of prognostic biomarker candidates, we compared proteomic profiles of primary tumor sections from early-stage HGSOC patients with either recurrent (RD) or non-recurrent disease (N = 4; each group) as a proof of concept study. In total, MALDI-IMS analysis resulted in 7537 spectra from the malignant tumor areas. Using receiver operating characteristic (ROC) analysis, 151 peptides were able to discriminate between patients with RD and non-RD (AUC > 0.6 or < 0.4; p < 0.01), and 13 of them could be annotated to proteins. Strongest expression levels of specific peptides linked to Keratin type1 and Collagen alpha-2(I) were observed and associated with poor prognosis (AUC > 0.7). These results confirm that in using IMS, we could identify new candidates to predict clinical outcome and treatment extent for patients with early-stage HGSOC.

Proof of Concept of an Endoscopic Sutureless Valve Sizer

2016 ◽  
Vol 11 (5) ◽  
pp. 337-341 ◽  
Author(s):  
Marco Vola ◽  
Juan Pablo Maureira ◽  
Vito Giovanni Ruggieri ◽  
Jean-François Fuzellier ◽  
Salvatore Campisi ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Early Stage ◽  
Ascending Aorta ◽  
Aortic Annulus ◽  
Laboratory Evaluation ◽  
Proof Of Concept ◽  
Valve Size ◽  
Sutureless Valve ◽  
Selection Of

Objective In this paper, we present an endoscopic expandable sizer conceived to allow thoracoscopic aortic valve replacement with a sutureless prosthesis using a dynamic sizing of the aortic annulus. Methods Ten aortic torsos were prepared using a five-trocar thoracoscopic setting. Once the aortotomy was performed and the aortic valve leaflets removed, the technical feasibility of the endoscopic sizing (introduction into the trocar, expansion into the aortic annulus, determination of the valve size, and retraction) with the device was assessed. In case of successful thoracoscopic sizing, endoscopic implantation of a sutureless valve (five LivaNova Perceval prosthesis and five Medtronic 3f Enable bioprosthesis) was performed. Before ascending aorta closure, we assessed the appropriate sealing of the bioprosthesis in the native annulus with camera visualization and a nerve hook inspection. Results All the 10 endoscopic sizings were technically feasible. The scheduled aortic sutureless valve implantations were successfully performed. In all cases, fitting and placement of the sutureless bio-prosthesis in the flaccid heart was satisfactory, with no paraprosthetic leakage detectable by the nerve hook. Conclusions The use of the endoscopic expandable sizer is technically possible. In this early-stage test in the flaccid heart, selection of the valve size was satisfactory during thoracoscopic sutureless aortic bioprosthesis implantation. Further laboratory evaluation with fluid dynamics (aortic root pressurization) will be performed before a clinical study is started.

scholarly journals Radiosynthesis of [18F]-Labelled Pro-Nucleotides (ProTides)

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 704
Author(s):  
Alessandra Cavaliere ◽  
Katrin C. Probst ◽  
Stephen J. Paisey ◽  
Christopher Marshall ◽  
Abdul K. H. Dheere ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Pet Imaging ◽  
Early Stage ◽  
Proof Of Concept ◽  
Synthesis Time ◽  
Positron Emission ◽  
Anti Cancer ◽  
Radiochemical Yields ◽  
Radiochemical Synthesis

Phosphoramidate pro-nucleotides (ProTides) have revolutionized the field of anti-viral and anti-cancer nucleoside therapy, overcoming the major limitations of nucleoside therapies and achieving clinical and commercial success. Despite the translation of ProTide technology into the clinic, there remain unresolved in vivo pharmacokinetic and pharmacodynamic questions. Positron Emission Tomography (PET) imaging using [18F]-labelled model ProTides could directly address key mechanistic questions and predict response to ProTide therapy. Here we report the first radiochemical synthesis of [18F]ProTides as novel probes for PET imaging. As a proof of concept, two chemically distinct radiolabelled ProTides have been synthesized as models of 3′- and 2′-fluorinated ProTides following different radiosynthetic approaches. The 3′-[18F]FLT ProTide was obtained via a late stage [18F]fluorination in radiochemical yields (RCY) of 15–30% (n = 5, decay-corrected from end of bombardment (EoB)), with high radiochemical purities (97%) and molar activities of 56 GBq/μmol (total synthesis time of 130 min.). The 2′-[18F]FIAU ProTide was obtained via an early stage [18F]fluorination approach with an RCY of 1–5% (n = 7, decay-corrected from EoB), with high radiochemical purities (98%) and molar activities of 53 GBq/μmol (total synthesis time of 240 min).

Myelotoxicity and Dose Intensity of Chemotherapy: Reporting Practices From Randomized Clinical Trials

2003 ◽  
Vol 1 (3) ◽  
pp. 440-454 ◽  
Author(s):  
David C. Dale ◽  
Gordon C. McCarter ◽  
Jeffrey Crawford ◽  
Gary H. Lyman
Keyword(s):  
Clinical Trials ◽  
Cancer Chemotherapy ◽  
Randomized Clinical Trials ◽  
Early Stage ◽  
Dose Intensity ◽  
Hematologic Toxicity ◽  
Intensity Data ◽  
Reporting Practices ◽  
Standard Procedures ◽  
Treatment Alternatives

Delivery of cancer chemotherapy is often limited by myelotoxicity, primarily neutropenia. As part of an effort to create a model to predict the risk of chemotherapy-induced neutropenia, we reviewed the reports of randomized clinical trials with more than 50 patients per arm in early-stage breast cancer (ESBC) and non-Hodgkin's lymphoma (NHL) published between 1990 and 2000. We observed that no hematologic toxicity data were reported in 39% and 34% of the ESBC and NHL trials, respectively. The remaining trials reported on hematologic toxicity in 16 different ways. When reported, rates of neutropenia, leukopenia, and hematotoxicity varied widely with the same and similar chemotherapy regimens. Dose-intensity data were not reported in 39% and 54% of ESBC and NHL trials, respectively. The majority of the remaining studies reported incomplete dose-intensity data such as percentages of patients completing all cycles or receiving a given percentage of planned dose intensity. Only 28% reported the mean or median relative dose intensity received by patients. Based on this review, we conclude that current practices for reporting chemotherapy treatments are inadequate for describing the risk of chemotherapy to patients or for quantitatively assessing the risk of treatment alternatives. We recommend that standard procedures for documenting and reporting hematologic toxicity and dose intensity in cancer chemotherapy trials be required for publication of chemotherapy trials.

Sign in / Sign up

Export Citation Format

Share Document