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International Journal of Gynecological... Jun 2022Antineoplastic agents can cause hypersensitivity reactions that may preclude further treatment, possibly compromising patient outcome if the tumor remains sensitive to...
OBJECTIVE
Antineoplastic agents can cause hypersensitivity reactions that may preclude further treatment, possibly compromising patient outcome if the tumor remains sensitive to such agent. Although desensitization protocols can be used to re-introduce agents after the development of a hypersensitivity reaction, these protocols vary across institutions. Our study evaluated the safety and efficacy of our desensitization protocol.
METHODS
All patients who underwent desensitization to platinum, taxane, liposomal doxorubicin, or trastuzumab between November 2016 and May 2021 after a prior hypersensitivity reaction to the specific agent were included in a retrospective review. The 12-step, outpatient desensitization protocol included pretreatment with a leukotriene receptor antagonist, antihistamines, and corticosteroids, as well as extended infusion times. Successful desensitization was defined as the completion of ≥3 cycles without discontinuation of the agent due to a hypersensitivity reaction.
RESULTS
A total of 186 eligible patients were included. Median age was 59.5 years (range 26-87). 155 (83%) patients were treated with platinum. 55 (30%) patients were treated for colorectal cancer and 52 (28%) for ovarian cancer. 104 (56%) patients completed ≥3 cycles of therapy during desensitization. The median infusion time was 380 min (range 325-360 min). The median number of desensitization cycles was 3, with 694 cycles completed among all patients. A total of 79 (42%) patients had a breakthrough hypersensitivity reaction during desensitization, 4 of whom required epinephrine, and 84 (45%) patients discontinued the agent undergoing desensitization due to progression of disease.
CONCLUSIONS
Our outpatient 12-step, institutional desensitization protocol for antineoplastic therapy proved safe and efficacious, with 56% of patients successfully completing ≥3 cycles and not requiring an inpatient admission.
PubMed: 35675969
DOI: 10.1136/ijgc-2022-003466 -
Systematic Reviews Jan 2018Neoadjuvant (chemo-)radiation has proven to improve local control compared to surgery alone, but this improvement did not translate into better overall or... (Meta-Analysis)
Meta-Analysis Review
Addition of platinum derivatives to neoadjuvant single-agent fluoropyrimidine chemoradiotherapy in patients with stage II/III rectal cancer: protocol for a systematic review and meta-analysis (PROSPERO CRD42017073064).
BACKGROUND
Neoadjuvant (chemo-)radiation has proven to improve local control compared to surgery alone, but this improvement did not translate into better overall or disease-specific survival. The addition of oxaliplatin to fluoropyrimidine-based neoadjuvant chemoradiotherapy holds the potential of positively affecting survival in this context since it has been proven effective in the palliative and adjuvant setting of colorectal cancer. Thus, the objective of this systematic review is to assess the efficacy, safety, and quality of life resulting from adding a platinum derivative to neoadjuvant single-agent fluoropyrimidine-based chemoradiotherapy in patients with Union for International Cancer Control stage II and III rectal cancer.
METHODS
MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials will be systematically searched to identify all randomized controlled trials comparing single-agent fluoropyrimidine-based chemoradiotherapy to combined neoadjuvant therapy including a platinum derivative. Predefined data on trial design, quality, patient characteristics, and endpoints will be extracted. Quality of included trials will be assessed according to the Cochrane Risk of Bias Tool, and the GRADE recommendations will be applied to judge the quality of the resulting evidence. The main outcome parameter will be survival, but also treatment toxicity, perioperative morbidity, and quality of life will be assessed.
DISCUSSION
The findings of this systematic review and meta-analysis will provide novel insights into the efficacy and safety of combined neoadjuvant chemoradiotherapy including a platinum derivative and may form a basis for future clinical decision-making, guideline evaluation, and research prioritization.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42017073064.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Humans; Neoadjuvant Therapy; Oxaliplatin; Quality of Life; Rectal Neoplasms; Survival
PubMed: 29357929
DOI: 10.1186/s13643-018-0678-9 -
Lasers in Medical Science Oct 2021Photochemical internalization (PCI) is a modified form of photodynamic therapy (PDT) that enhances the efficacy of therapeutic agents in a site and temporal specific... (Review)
Review
Photochemical internalization (PCI) is a modified form of photodynamic therapy (PDT) that enhances the efficacy of therapeutic agents in a site and temporal specific manner in both in vitro and in vivo publications. The purpose of the study reported here was to evaluate the benefits of a modified PCI protocol in a 3D rat glioma spheroid model. In the modified protocol, F98 glioma cells were incubated with photosensitizer (AlPcS) prior to spheroid generation, as opposed to post-spheroid formation photosensitizer exposure commonly used in conventional protocols. The efficacy of both bleomycin and doxorubicin PCI was evaluated using either the conventional or modified protocols. The formed spheroids were then exposed to light treatment from a diode laser, λ= 670 nm. Spheroid growth was monitored for a period of 14 days. The results of spheroid growth assays showed that there was no statistically significant difference in PCI efficacy between the conventional and modified protocols for both of the drugs tested. The direct PDT effect was significantly reduced using the modified protocol. Therefore, due to its several advantages, the modified protocol is recommended for evaluating the efficacy of PCI in tumor spheroid models.
Topics: Animals; Bleomycin; Cell Line, Tumor; Glioma; Photochemotherapy; Photosensitizing Agents; Rats
PubMed: 34185168
DOI: 10.1007/s10103-021-03332-y -
Journal of Veterinary Internal Medicine Mar 2023Evidence supporting the effectiveness of therapeutic protocols for nonassociative immune-mediated hemolytic anemia (na-IMHA) is weak.
BACKGROUND
Evidence supporting the effectiveness of therapeutic protocols for nonassociative immune-mediated hemolytic anemia (na-IMHA) is weak.
HYPOTHESIS/OBJECTIVES
Investigate the efficacy of various drugs in na-IMHA.
ANIMALS
Two hundred forty-two dogs.
METHODS
Multi-institutional retrospective study (2015-2020). Immunosuppressive effectiveness was determined by time to packed cell volume (PCV) stabilization and duration of hospitalization through analysis by mixed model linear regression. Occurrence of disease relapse, death, and antithrombotic effectiveness, were analyzed using mixed model logistic regression.
RESULTS
Use of corticosteroids vs a multi-agent protocol had no effect on time to PCV stabilization (P = .55), duration of hospitalization (P = .13), or case fatality (P = .06). A higher rate of relapse (P = .04; odds ratio: 3.97; 95% confidence interval [CI]: 1.06-14.8) was detected in dogs receiving corticosteroids (11.3%) during follow-up (median: 28.5 days, range: 0-1631 days) compared to multiple agents (3.1%) during follow up (median: 47.0 days, range: 0-1992 days). When comparing drug protocols, there was no effect on time to PCV stabilization (P = .31), relapse (P = .44), or case fatality (P = .08). Duration of hospitalization was longer, by 1.8 days (95% CI: 0.39-3.28 days), for the corticosteroid with mycophenolate mofetil group (P = .01) compared to corticosteroids alone. Use of clopidogrel vs multiple agents had no effect on development of thromboses (P ≥ .36).
CONCLUSIONS AND CLINICAL IMPORTANCE
Addition of a second immunosuppressive agent did not alter immediate outcome measures but might be associated with a reduction in relapse. Use of multiple antithrombotic agents did not reduce incidence of thrombosis.
Topics: Animals; Dogs; Adrenal Cortex Hormones; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Dog Diseases; Immunosuppressive Agents; Recurrence; Retrospective Studies
PubMed: 36809664
DOI: 10.1111/jvim.16652 -
American Journal of Hypertension Jul 2022To compare prevalence of hypertension and stage II hypertension assessed by 2 blood pressure (BP) observation protocols.
Differences in Hypertension and Stage II Hypertension by Demographic and Risk Factors, Obtained by Two Different Protocols in US Adults: National Health and Nutrition Examination Survey, 2017-2018.
BACKGROUND
To compare prevalence of hypertension and stage II hypertension assessed by 2 blood pressure (BP) observation protocols.
METHODS
Participants aged 18 years and older (n = 4,689) in the National Health and Nutrition Examination Survey (NHANES 2017-2018) had their BP measured following 2 protocols: the legacy auscultation protocol (AP) and oscillometric protocol (OP). The order of protocols was randomly assigned. Prevalence estimates for hypertension (BP ≥130/80 mm Hg or use of medication for hypertension) and stage II hypertension (BP ≥140/90 mm Hg) were determined overall, by demographics, and by risk factors for each protocol. Ratios (OP% ÷ AP%) and kappa statistics were calculated.
RESULTS
Age-adjusted hypertension prevalence was 44.5% (95% confidence interval [CI]: 41.1%-48.0%) using OP and 45.1% (95% CI: 41.5%-48.7%) using AP, prevalence ratio = 0.99 (95% CI = 0.94-1.04). Age-adjusted stage II hypertension prevalence was 15.8% (95% CI: 13.6%-18.2%) using AP and 17.1% (95% CI: 14.7%-19.7%) using OP, prevalence ratio = 0.92 (95% CI = 0.81-1.04). For both hypertension and stage II hypertension, the prevalence ratios by demographics and by risk factors all included unity in their 95% CI, except for stage II hypertension in adults 60+ years (ratio: 0.88 [95% CI: 0.78-0.98]). Kappa for agreement between protocols for hypertension and stage II hypertension was 0.75 (95% CI = 0.71-0.79) and 0.67 (95% CI = 0.61-0.72), respectively.
CONCLUSIONS
In adults and for nearly all subcategories there were no significant differences in prevalence of hypertension and stage II hypertension between protocols, indicating that protocol change may not affect the national prevalence estimates of hypertension and stage II hypertension.
Topics: Adult; Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Nutrition Surveys; Prevalence; Risk Factors; United States
PubMed: 35333925
DOI: 10.1093/ajh/hpac042 -
Nihon Rinsho. Japanese Journal of... Feb 2015
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Remission Induction; Rhabdomyosarcoma; Vincristine
PubMed: 25831844
DOI: No ID Found -
The Oncologist May 2017Combining targeted and cytotoxic agents has the potential to improve efficacy and attenuate resistance for metastatic cancer. Information regarding safe starting doses... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Combining targeted and cytotoxic agents has the potential to improve efficacy and attenuate resistance for metastatic cancer. Information regarding safe starting doses for clinical trials of novel three-drug combinations is lacking.
MATERIALS AND METHODS
Published phase I-III adult oncology clinical trials of three-drug combinations involving a targeted agent were identified by PubMed search (January 1, 2010 to December 31, 2013). A dose percentage was calculated to compare the dose used in combination to the single agent recommended dose: (U.S. Food and Drug Administration-approved/recommended phase II dose/maximum tolerated dose). The additive dose percentage was the sum of the dose percentages for each drug in the combination.
RESULTS
A total of 37,763 subjects and 243 drug combinations were included. Only 28% of studies could give each of the three agents at 100%. For combinations involving two targeted agents and a cytotoxic agent, the lowest starting additive dose percentage was 133%, which increased to 250% if two antibodies were included. For combinations of one targeted agent and two cytotoxic agents, the lowest additive safe dose percentage was 137%. When both cytotoxic agents were held at 100%, as occurred in 56% of studies (which generally used cytotoxic doublets with known combination safety dosing), the lowest safe dose percentage was 225% (providing that a histone deacetylase inhibitor was not the targeted agent).
CONCLUSION
These findings serve as a safe starting point for dosing novel three-drug combinations involving a targeted agent in clinical trials and practice. 2017;22:576-584 IMPLICATIONS FOR PRACTICE: Targeted and cytotoxic drug combinations can improve efficacy and overcome resistance. More knowledge of safe starting doses would facilitate use of combinations in clinical trials and practice. Analysis of 37,763 subjects (243 combinations) showed three drugs could be safely administered, but less than 30% of combinations could include all three drugs at full dose. Dose reductions to 45% of the dose of each single agent may be required. Combinations involving two antibodies required fewer dose reductions, and the use of established cytotoxic doublets made initial dose assignment easier.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Dose-Response Relationship, Drug; Histone Deacetylase Inhibitors; Humans; Neoplasms
PubMed: 28424323
DOI: 10.1634/theoncologist.2016-0357 -
Pacing and Clinical Electrophysiology :... Jun 2020Most atrial fibrillation (AF) ablations are performed with general anesthesia (GA). The ideal GA protocol is unknown, but it affects ablation outcomes and laboratory...
BACKGROUND
Most atrial fibrillation (AF) ablations are performed with general anesthesia (GA). The ideal GA protocol is unknown, but it affects ablation outcomes and laboratory utilization. We sought to report a GA protocol used at a high-volume center, with special consideration on efficiency and optimization of mapping and ablation conditions.
METHODS
Our protocol consists of propofol as sole anesthetic agent and analgesia with Fentanyl. IV fluids are minimized. After transseptal access, the right phrenic nerve is tagged, rocuronium is given, and redosing avoided. Ventilation is modulated to optimize mapping and ablation. After ablation, isoproterenol is infused for 20 min. After 10 min, propofol is gradually decreased and ventilation set to SIMV 8 breaths/min to promote spontaneous breathing, and then switched to pressure support and propofol stopped. Paralysis is reversed and furosemide given. Patient is extubated once meeting standard criteria.
RESULTS
A total of 1286 patients underwent AF ablation from January 2017 to December 2018 using the protocol. Mean age was 66 years (41% paroxysmal AF, CHADS2Vasc 2.6). Total procedure time was 86 min. Median time to extubation was 9 min (first and third quartile 6-16) after procedure completed, with total anesthesia time of 116 min. On average 370 mL of fluids were given by anesthesia. Only one patient who had heart failure required reintubation with no other anesthesia-related complications seen.
CONCLUSION
Our GA protocol was specifically designed for AF ablation. It was safe and led to efficient recovery and extubation times. It maximizes laboratory utilization time without compromising safety.
Topics: Aged; Anesthesia, General; Anesthetics, Intravenous; Atrial Fibrillation; Cardiac Surgical Procedures; Catheter Ablation; Clinical Protocols; Female; Humans; Male; Middle Aged; Propofol; Retrospective Studies
PubMed: 32333408
DOI: 10.1111/pace.13928 -
European Radiology Jan 2017To evaluate the feasibility, image quality, and radiation dose of automatic spectral imaging protocol selection (ASIS) and adaptive statistical iterative reconstruction...
OBJECTIVE
To evaluate the feasibility, image quality, and radiation dose of automatic spectral imaging protocol selection (ASIS) and adaptive statistical iterative reconstruction (ASIR) with reduced contrast agent dose in abdominal multiphase CT.
METHODS
One hundred and sixty patients were randomly divided into two scan protocols (n = 80 each; protocol A, 120 kVp/450 mgI/kg, filtered back projection algorithm (FBP); protocol B, spectral CT imaging with ASIS and 40 to 70 keV monochromatic images generated per 300 mgI/kg, ASIR algorithm. Quantitative parameters (image noise and contrast-to-noise ratios [CNRs]) and qualitative visual parameters (image noise, small structures, organ enhancement, and overall image quality) were compared.
RESULTS
Monochromatic images at 50 keV and 60 keV provided similar or lower image noise, but higher contrast and overall image quality as compared with 120-kVp images. Despite the higher image noise, 40-keV images showed similar overall image quality compared to 120-kVp images. Radiation dose did not differ between the two protocols, while contrast agent dose in protocol B was reduced by 33 %.
CONCLUSION
Application of ASIR and ASIS to monochromatic imaging from 40 to 60 keV allowed contrast agent dose reduction with adequate image quality and without increasing radiation dose compared to 120 kVp with FBP.
KEY POINTS
• Automatic spectral imaging protocol selection provides appropriate scan protocols. • Abdominal CT is feasible using spectral imaging and 300 mgI/kg contrast agent. • 50-keV monochromatic images with 50 % ASIR provide optimal image quality.
Topics: Contrast Media; Feasibility Studies; Female; Humans; Male; Middle Aged; Prospective Studies; Radiation Dosage; Radiographic Image Enhancement; Radiographic Image Interpretation, Computer-Assisted; Radiography, Abdominal; Tomography, X-Ray Computed
PubMed: 27097790
DOI: 10.1007/s00330-016-4349-8 -
PLoS Computational Biology Oct 2022Language interfaces with many other cognitive domains. This paper explores how interactions at these interfaces can be studied with deep learning methods, focusing on...
Language interfaces with many other cognitive domains. This paper explores how interactions at these interfaces can be studied with deep learning methods, focusing on the relation between language emergence and visual perception. To model the emergence of language, a sender and a receiver agent are trained on a reference game. The agents are implemented as deep neural networks, with dedicated vision and language modules. Motivated by the mutual influence between language and perception in cognition, we apply systematic manipulations to the agents' (i) visual representations, to analyze the effects on emergent communication, and (ii) communication protocols, to analyze the effects on visual representations. Our analyses show that perceptual biases shape semantic categorization and communicative content. Conversely, if the communication protocol partitions object space along certain attributes, agents learn to represent visual information about these attributes more accurately, and the representations of communication partners align. Finally, an evolutionary analysis suggests that visual representations may be shaped in part to facilitate the communication of environmentally relevant distinctions. Aside from accounting for co-adaptation effects between language and perception, our results point out ways to modulate and improve visual representation learning and emergent communication in artificial agents.
Topics: Language; Communication; Semantics; Cognition; Visual Perception
PubMed: 36315590
DOI: 10.1371/journal.pcbi.1010658