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Ophthalmology. Retina Feb 2021To characterize the rates of panretinal photocoagulation (PRP) and anti-vascular endothelial growth factor (VEGF) medications before and after publication of the...
PURPOSE
To characterize the rates of panretinal photocoagulation (PRP) and anti-vascular endothelial growth factor (VEGF) medications before and after publication of the Diabetic Retinopathy Clinical Research Network protocol S.
DESIGN
A retrospective, cross-sectional study from January 2012, through September 2019, using a nationally representative claims-based database, Clinformatics Data Mart Database (OptumInsight, Eden Prairie, MN).
PARTICIPANTS
Eyes newly diagnosed with proliferative diabetic retinopathy (PDR), continuous enrollment, and no prior treatment with PRP or anti-VEGF agents.
METHODS
Interrupted time series regression analysis was performed to identify the annual change in treatment rates before and after the publication of Protocol S (November 2015).
MAIN OUTCOME MEASURES
Annual rates of anti-VEGF or PRP treatments per 1000 treated eyes with PDR.
RESULTS
From 2012 through 2019, 10 035 PRP or anti-VEGF treatments were administered to 3685 PDR eyes. Of these, 63.6% (n = 6379) were anti-VEGF agents, and 36.4% (n = 3656) were PRP treatments. Throughout treatment, 88.7% of eyes treated with anti-VEGF received the same agent and 7.7% were treated with both PRP and anti-VEGF agents. Panretinal photocoagulation rates declined from 784/1000 treated eyes in 2012 to 566/1000 in 2019 (pre-Protocol S: β = -32 vs. post-Protocol S: -77; P = 0.005), whereas anti-VEGF rates increased from 876/1000 in 2012 to 1583/1000 in 2019 (β = -48 vs. 161, respectively; P = 0.001). Panretinal photocoagulation rates in diabetic macular edema (DME) eyes did not significantly differ from 474/1000 in 2012 to 363/1000 in 2019 (β = -9 vs. -58 respectively; P = 0.091), and anti-VEGF rates increased from 1533/1000 in 2012 to 2096/1000 in 2019 (β = -57 vs. 187; P = 0.043). In eyes without DME, PRP use declined from 1017/1000 in 2012 to 707/1000 in 2019 (β = -31 vs. -111, respectively; P < 0.001), and anti-VEGF use increased from 383/1000 in 2012 to 1226/1000 in 2019 (β = -48 vs. 140, respectively; P < 0.001).
CONCLUSIONS
Following the publication of Protocol S, PRP rates decreased, while anti-VEGF rates increased. Panretinal photocoagulation rates did not significantly change among eyes with DME. Our findings indicate the impact that randomized controlled trials can have on real-world practice patterns.
Topics: Aged; Angiogenesis Inhibitors; Cross-Sectional Studies; Diabetic Retinopathy; Female; Follow-Up Studies; Humans; Intravitreal Injections; Laser Coagulation; Male; Middle Aged; Ranibizumab; Retina; Retrospective Studies; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity
PubMed: 32693033
DOI: 10.1016/j.oret.2020.07.018 -
IEEE Transactions on Neural Networks... Aug 2023Communicating agents with each other in a distributed manner and behaving as a group are essential in multi-agent reinforcement learning. However, real-world multi-agent...
Communicating agents with each other in a distributed manner and behaving as a group are essential in multi-agent reinforcement learning. However, real-world multi-agent systems suffer from restrictions on limited bandwidth communication. If the bandwidth is fully occupied, some agents are not able to send messages promptly to others, causing decision delay and impairing cooperative effects. Recent related work has started to address the problem but still fails in maximally reducing the consumption of communication resources. In this article, we propose an event-triggered communication network (ETCNet) to enhance communication efficiency in multi-agent systems by communicating only when necessary. For different task requirements, two paradigms of the ETCNet framework, event-triggered sending network (ETSNet) and event-triggered receiving network (ETRNet), are proposed for learning efficient sending and receiving protocols, respectively. Leveraging the information theory, the limited bandwidth is translated to the penalty threshold of an event-triggered strategy, which determines whether an agent at each step participates in communication or not. Then, the design of the event-triggered strategy is formulated as a constrained Markov decision problem and reinforcement learning finds the feasible and optimal communication protocol that satisfies the limited bandwidth constraint. Experiments on typical multi-agent tasks demonstrate that ETCNet outperforms other methods in reducing bandwidth occupancy and still preserves the cooperative performance of multi-agent systems at the most.
PubMed: 34723813
DOI: 10.1109/TNNLS.2021.3121546 -
Trials Mar 2023Immunosuppression in transplantation continues to be associated with a multitude of adverse effects. Induction of immune tolerance may be a viable strategy to reduce...
BACKGROUND
Immunosuppression in transplantation continues to be associated with a multitude of adverse effects. Induction of immune tolerance may be a viable strategy to reduce dependence on immunosuppression. Various trials are currently underway to assess the efficacy of this strategy. However, long-term safety data for these immune tolerance regimes has yet to be established.
METHODS/DESIGN
At the completion of primary follow-up of various Medeor kidney transplant studies, subjects receiving cellular immunotherapy products will be followed annually as per protocolized schedule for up to an additional 84 months (7 years) to evaluate long-term safety. Long-term safety will be assessed by summarizing incidence of serious adverse events, adverse events leading to study withdrawal and hospitalization rates.
DISCUSSION
This extension study will be an important step in evaluating safety issues pertaining to immune tolerance regimens, long-term effects of which are largely unknown. These data are essential for furthering an unrealized goal of kidney transplantation- graft longevity without the adverse effects from long-term immunosuppression. The study design utilizes the methodology of a master protocol, wherein multiple therapies can be assessed simultaneously with accompanied gathering of long-term safety data.
Topics: Humans; Kidney Transplantation; Immunosuppression Therapy; Immunosuppressive Agents; Graft Rejection
PubMed: 36899436
DOI: 10.1186/s13063-023-07204-4 -
Journal of Investigational Allergology... 2016Desensitization protocols for patients with immediate hypersensitivity reactions (IHSRs) have proven to be effective, but they are not widely used in clinical practice...
BACKGROUND AND OBJECTIVE
Desensitization protocols for patients with immediate hypersensitivity reactions (IHSRs) have proven to be effective, but they are not widely used in clinical practice because of impracticalities such as high cost, long procedure duration, and a lack of trained personnel. We aimed to determine the clinical characteristics of oxaliplatin-induced IHSRs and assess measures to protect against these reactions and to validate a new practical desensitization protocol.
METHODS
We retrospectively reviewed 2640 cases of oxaliplatin IHSRs in 271 oxaliplatin users and prospectively used a newly designed desensitization protocol 32 times in 12 patients with hypersensitivity to platinum-based chemotherapy. The protocol consisted of increases in infusion rate every 15 minutes, regardless of the concentration of the chemotherapy agent in the infusion bags.
RESULTS
Of the 271 patients administered oxaliplatin, 45 (16.6%) experienced IHSRs. Of 39 patients who experienced an IHSR but needed to continue oxaliplatin, 6 (15.4%) stopped treatment due to the reaction, and 33 (84.6%) continued despite the risk of further reactions. The new desensitization protocol was successfully completed in 12 patients (100%), but it was ineffective in 3 patients (all with a negative skin prick test), who experienced fever without urticaria.
CONCLUSIONS
Many patients who experience oxaliplatin-induced IHSRs are required to stop first-line oxaliplatin-based chemotherapy or to continue without desensitization, with the associated risks. Our new desensitization protocol is practical and easy to use in clinical practice.
Topics: Adult; Antineoplastic Agents; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Immediate; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Skin Tests
PubMed: 27326984
DOI: 10.18176/jiaci.0038 -
Proceedings of SPIE--the International... Feb 2020Fluorescent molecular-guided surgery (FGS) is at a tipping point in terms of clinical approval and adoption in a number cancer applications, with ongoing phase 0 and...
Task-based evaluation of fluorescent-guided cancer surgery as a means of identifying optimal imaging agent properties in the context of variability in tumor- and healthy-tissue physiology.
Fluorescent molecular-guided surgery (FGS) is at a tipping point in terms of clinical approval and adoption in a number cancer applications, with ongoing phase 0 and phase 1 clinical trials being carried out in a wide range of cancers using a wide range of agents. The pharmacokinetics of each of these agents and the physiology of these cancers can differ vastly on a patient-to-patient basis, bringing to question: how can one fairly compare different methodologies (defined as the combination of imaging agent, system, and protocol) and how can existing methodologies be further optimized? To this point, little methodology comparison has been carried out, and the majority of FGS optimization has concerned system development-on the level of maximizing signal-to-noise, dynamic detection range, and sensitivity-independently from traditional agent development-in terms of fluorophore brightness, toxicity, solubility, and binding affinity and specificity. Here we propose an inclusion of tumor and healthy tissue physiology (blood flow, vascular permeability, specific and nonspecific binding sites, extracellular matrix, interstitial pressure, etc…) variability into the optimization process and re-establish well-described task-based metrics for methodology optimization and comparing quality of one methodology to another. Two salient conclusions were identified: (1) contrast-to-background variability is a simple metric that correlates with difficult-to-carry-out task-based metrics for comparing methodologies, and (2) paired-agent imaging protocols offer unique advantages over single-imaging-agent studies for mitigating confounding tumor and background physiology variability.
PubMed: 33568879
DOI: 10.1117/12.2546700 -
Current Opinion in Ophthalmology May 2016Diabetic retinopathy and diabetic macular edema (DME) are common eye diseases leading to vision loss. The Diabetic Retinopathy Clinical Research Network (DRCRnet), a... (Review)
Review
PURPOSE OF REVIEW
Diabetic retinopathy and diabetic macular edema (DME) are common eye diseases leading to vision loss. The Diabetic Retinopathy Clinical Research Network (DRCRnet), a collaboration of private and academic practices supported by the National Eye Institute and the National Institute of Diabetes, Digestive and Kidney Diseases has studied diabetic eye disease for 13 years. This review will discuss the network's findings over the last year, when some of its most important contributions were reported.
RECENT FINDINGS
The DRCRnet reported intravitreal bevacizumab, ranibizumab and aflibercept all improve visual acuity in DME. With baseline vision of 20/30 to 20/40, all agents had similar efficacy. With baseline vision of 20/50 or worse, aflibercept resulted in superior visual improvement. Protocol S, which compared panretinal photocoagulation with intravitreal injections of ranibizumab for proliferative diabetic retinopathy (PDR), found vision outcomes and surgery rates were not inferior in the injection group. Secondary outcomes indicate improved functional results with ranibizumab supporting injections as a possible alternative treatment for PDR.
SUMMARY
The DRCRnet has helped clarify the role of various treatments for both DME and PDR, and will continue to evaluate treatments for these vision-threatening conditions.
Topics: Diabetic Retinopathy; Hemorrhage; Humans; Laser Coagulation; Vision Disorders; Visual Acuity
PubMed: 26913740
DOI: 10.1097/ICU.0000000000000262 -
Actas Dermo-sifiliograficas Mar 2009Infliximab is a chimeric monoclonal antibody that binds to and blocks tumor necrosis factor alpha and is the most effective biologic agent approved for the treatment of... (Review)
Review
[Reactions to infliximab infusions in dermatologic patients: consensus statement and treatment protocol. Working Group of the Grupo Español de Psoriasis de la Academia Española de Dermatología y Venereología ].
Infliximab is a chimeric monoclonal antibody that binds to and blocks tumor necrosis factor alpha and is the most effective biologic agent approved for the treatment of moderate-to-severe psoriasis. It is administered by intravenous infusion, usually in day hospitals on an outpatient basis. The main problem with the administration of infliximab is the possibility of infusion reactions, which may be immediate or delayed; these reactions are related to the immunogenicity of this monoclonal antibody, leading to the production of anti-infliximab antibodies. Infusion reactions to infliximab are not usually anaphylactic (ie, they are not mediated by immunoglobulin E), and re-exposure of the patient using specific protocols to prevent and treat these reactions is therefore possible. The extensive experience in the use of infliximab for the treatment of rheumatic conditions and chronic inflammatory bowel disease has made it possible to develop infusion reaction management protocols; these can be applied to dermatologic patients, who constitute a growing proportion of patients treated with intravenous biological agents. The aim of this review is to draw up a consensus protocol for the treatment of infusion reactions in dermatologic patients treated with infliximab.
Topics: Adrenal Cortex Hormones; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Arthritis; Clinical Protocols; Contraindications; Dermatologic Agents; Drug Hypersensitivity; Histamine Antagonists; Humans; Infliximab; Infusions, Intravenous; Psoriasis; Recurrence; Respiratory Insufficiency; Time Factors; Tumor Necrosis Factor-alpha
PubMed: 19445874
DOI: 10.1016/s0001-7310(09)70227-3 -
Journal of Traditional Chinese Medicine... Feb 2022To evaluate the anti-oxidant, enzyme inhibition, anti-pyretic, anti-inflammatory and anti-diabetic activities of Iris albicans.
OBJECTIVE
To evaluate the anti-oxidant, enzyme inhibition, anti-pyretic, anti-inflammatory and anti-diabetic activities of Iris albicans.
METHODS
Anti-oxidant assay was evaluated using DPPH (2, 2-diphenyl-1-picrylhydrazyl) radical scavenging and ABTS (2, 2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) inhibitory protocol while enzyme inhibitory assay was evaluated by lipoxygenase and cyclooxygenase-2 inhibitory protocol respectively. Antipyretic, anti-inflammatory and anti-diabetic potential was evaluated using brewer's yeast induced pyrexia, carrageenan induced paw edema and streptozocin induced diabetes protocols respectively. Serum biochemical parameters were monitored for the period of study.
RESULTS
The anti-oxidant activity of chloroform fraction of Iris albicans showed the highest scavenging potential against DPPH and ABTS while the maximum inhibitory action recorded against lipo-oxygenase and cyclooxygenase-2 enzymes was shown by n-hexane and chloroform fractions respectively. The anti-pyretic potential of the crude methanolic extract showed dose dependent activity in reducing pyrexia, thereby when the dose was increased the anti-pyretic effect was also enhanced. The anti-inflammatory action of the crude methanolic extract administered at the dose of 300 mg/kg was significant at 1 h after its administration, which was found maintained up to 5 h. Similarly the anti-diabetic effect of the crude methanolic extract administered at the dose of 200 and 300 mg/kg was noted highly significant at day 6 and was found well maintained throughout the study time period up to 10 days. Significant (P < 0.001) improvement appeared in hemoglobin, protein, cholesterol, triglycerides, urea, creatinine, HDL and LDL of extract treated diabetic mice.
CONCLUSION
From this data it could be concluded that Iris albicans have significant anti-oxidant, enzyme inhibition, ant-pyretic, anti-inflammatory and anti-diabetic potential.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Chloroform; Cyclooxygenase 2; Diabetes Mellitus, Experimental; Fever; Humans; Iris Plant; Methanol; Mice; Plant Extracts
PubMed: 35322627
DOI: 10.19852/j.cnki.jtcm.2022.01.001 -
Oral Health & Preventive Dentistry Jan 2021The aim of the present research was to analyse the effects of two bleaching agents, on the enamel crystallography by means of X-ray diffraction.
PURPOSE
The aim of the present research was to analyse the effects of two bleaching agents, on the enamel crystallography by means of X-ray diffraction.
MATERIAL AND METHODS
Twelve human sound posterior teeth, were collected for the present study (n = 12) and from each tooth two enamel slabs were obtained and randomly assigned to one of two different bleaching protocols. The first protocol involved an in-office bleaching agent (hydrogen peroxide 37.5%/ SDI Polaoffice+), and the second an at-home whitening product (carbamide peroxide 16%/ PHILIPS Zoom! NiteWhite). X-ray diffraction readings were made before and after applying the treatments in order to analyse the peak intensity and crystal domain size. Additionally, scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were carried out to identify the composition correctly. Statistical analysis included repeated measures analysis of variance (p ≤ 0.05). Results: Peak intensity in spectra obtained by X-ray diffraction had a tendency to diminish, mostly in the at-home bleaching group. The analysed data approximate a decrease in the crystal domain size among the samples treated for longer periods of time. Statistical analysis depicted no statistically significant differences among the experimental groups (p ≥ 0.05). Conclusions: Crystal domain size had a tendency to decrease, mostly when the enamel was treated by bleaching gels that had to be applied by prolonged periods of time.
Topics: Carbamide Peroxide; Crystallography; Dental Enamel; Gels; Humans; Hydrogen Peroxide; Microscopy, Electron, Scanning; Tooth Bleaching; Tooth Bleaching Agents
PubMed: 33491373
DOI: 10.3290/j.ohpd.b875523 -
Annals of Oncology : Official Journal... 2003Docetaxel-based chemotherapy appears to have considerable promise in advanced gastric cancer. In phase II studies of single agent docetaxel, response rates (RRs) of 17%... (Review)
Review
Docetaxel-based chemotherapy appears to have considerable promise in advanced gastric cancer. In phase II studies of single agent docetaxel, response rates (RRs) of 17% to 24% have been achieved in previously untreated patients. Importantly, RRs of 20% to 22% are seen in second-line treatment. Work by a Swiss and Italian collaborative group has shown that the combination of docetaxel 85 mg/m(2) with cisplatin 75 mg/m(2) every 3 weeks is quite active, achieving an RR of 55% and median survival of 9 months. Hematotoxicity was the main adverse event but was manageable. In other respects the docetaxel/cisplatin doublet (TC) was relatively well tolerated. The same group demonstrated that continuous infusion of 5-fluorouracil (5-FU) 300 mg/m(2) can be given on 2 weeks out of 3 to patients receiving TC. The addition of 5-FU, by this schedule, to TC (TCF) does not increase hematological toxicity, and does not compromise the tolerability of TC. An overall RR of 55% has been reported with TCF. A randomized phase II comparison of TC or TCF versus an ECF (epirubicin/cisplatin/5-FU) control arm is ongoing and should lead to a randomized phase III trial comparing TC or TCF with ECF. In an already completed international randomized phase II comparison of TC versus TCF (TAX-325), the three-drug combination proved significantly more active (RR 54% versus 32% with TC, among patients treated per protocol). Time to progression was also longer for TCF. Gastrointestinal (but not hematological) toxicity was less with TC. TCF was chosen for ongoing phase III comparison against a control 5-FU/cisplatin arm. It is possible that data from these randomized studies will confirm the value of docetaxel-based chemotherapy in advanced gastric cancer and that docetaxel combinations will also be effective in the multidisciplinary efforts to cure earlier stage cancer.
Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Docetaxel; Europe; Fluorouracil; Humans; Multicenter Studies as Topic; Paclitaxel; Research Design; Stomach Neoplasms; Taxoids; Treatment Outcome
PubMed: 12810457
DOI: 10.1093/annonc/mdg728