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Trials May 2021Chemoprophylactics against emerging epidemic and pandemic infectious diseases offer potential for prevention but require efficacy and safety analysis before widespread... (Review)
Review
BACKGROUND
Chemoprophylactics against emerging epidemic and pandemic infectious diseases offer potential for prevention but require efficacy and safety analysis before widespread use can be recommended. Chemoprophylaxis with repurposed drugs enables deployment ahead of development of novel vaccines. It may have particular utility as a stopgap ahead of vaccine deployment or when vaccines become less effective on virus variants, in countries where there may be structural inaccessibility to vaccines or in specific risk-groups. Rapid implementation of robust trial designs is a persistent challenge in epidemics. We systematically reviewed SARS-CoV-2 and COVID-19 chemoprophylaxis trial registrations from the first 21 weeks of the pandemic to critically appraise significant design features and alignment of study populations to clinical and public health uses, and describe candidate chemoprophylactic agents.
METHODS
We searched online international trial databases from 31 Dec 2019 to 26 May 2020 using keywords "proph*" or "prevention". Trial protocols assessing efficacy of chemoprophylactic agents for COVID-19 were included. Trial components were screened for eligibility and relevant studies extracted. Key trial design features were assessed.
RESULTS
We found 76 chemoprophylaxis study registrations, proposing enrolment of 208,367 people with median size of 490 (IQR 262-1710). A randomised design was specified for 63 trials, 61 included a control group and total proposed enrolment size was 197,010, median 600 (IQR 236-1834). Four protocols provided information on effect size sought. We estimate that for a control group attack rate of 10%, 66% of trials would be underpowered to detect a 50% effect size, and 97% of trials would be underpowered to detect a 30% effect size (at the 80% level). We found evidence of adaptive design in one trial registration only. Laboratory-confirmed infection with or without symptoms was the most common primary outcome. Polymerase chain reaction testing alone was used in 46% of trials, serological testing in 6.6% and 14.5% used both testing methods. Healthcare workers were the target population in 52/79 (65.8%) trials: 49 pre-exposure prophylaxis (PrEP) and 3 post-exposure prophylaxis (PEP). Sixteen trials (20.3%) planned PEP in close contacts. Five studies (6.3%) considered chemoprophylaxis in clinical-risk patients. Older adults were the focus of recruitment in only 3 (3.8%) studies (all long-term care facilities). Two (2.5%) studies of PrEP in the general population included older adults. Hydroxychloroquine was the most common candidate agent in 55/79 trials (69.6%), followed by chloroquine (4/79, 5.0%) and lopinavir/ritonavir (3/79, 3.8%).
CONCLUSION
Many registered COVID-19 chemoprophylaxis efficacy trials were underpowered to detect clinically meaningful protection at epidemiologically informed attack rates. This, compounded with the time that has taken to organise these trials as compared to the rapid development of COVID-19 vaccines, has rendered these trials of marginal importance. International coordination mechanisms and collaboration is required. Supporting the design of feasible chemoprophylaxis trials, large enough to generate strong evidence, early on in an epidemic using adaptive platform trial designs will allow structured entry and exit of candidate agents and rapid stand-up of trial infrastructure.
REVIEW PROTOCOL REGISTRATION
Our protocol is registered at https://www.osf.io/vp56f on May 20, 2020.
Topics: Aged; Antiviral Agents; COVID-19; COVID-19 Vaccines; Chemoprevention; Humans; Pandemics; SARS-CoV-2; Treatment Outcome
PubMed: 34051840
DOI: 10.1186/s13063-021-05323-4 -
Dental Materials : Official Publication... Mar 2024To assess visually and quantitatively the contributions of the adhesive layer photopolymerization and the subsequent resin composite increment to spatio-temporal maps of...
OBJECTIVES
To assess visually and quantitatively the contributions of the adhesive layer photopolymerization and the subsequent resin composite increment to spatio-temporal maps of temperature at five different cavity locations, subjected to two irradiance curing protocols: standard and ultra-high.
METHODS
Caries-free molars were used to obtain 40, 2 mm thick dentin slices, randomly assigned to groups (n = 5). These slices were incorporated within 3D-printed model cavites, 4 mm deep, restored with Adhese® Universal bonding agent and 2 mm thick Tetric® Powerfill resin composite, and photocured sequentially, as follows: G1: control-empty cavity; G2: adhesive layer; G3 composite layer with no adhesive; and G4 composite layer with adhesive. The main four groups were subdivided based on two curing protocols, exposed either to standard 10 s (1.2 W/cm) or Ultra high 3 s (3 W/cm) irradiance modes using a Bluephase PowerCure LCU. Temperature maps were obtained, via a thermal imaging camera, and numerically analyzed at 5 locations. The data were analyzed using two-way ANOVA followed by multiple one-way ANOVA, independent t-tests and Tukey post-hoc tests (α = 0.05). T, ΔT, T (integrated area under the curve) and time-to-reach-maximum-temperature were evaluated.
RESULTS
Two-way ANOVA showed that there was no significant interaction between light-curing time and location on the measured parameters (p > 0.05), except for the time-to-reach-maximum-temperature (p < 0.05). Curing the adhesive layer alone with the 10 s protocol resulted in a significantly increased pulpal roof temperature compared to 3 s cure (p < 0.05). Independent T-tests between G3 and G4, between 3 s and 10 s, confirmed that the adhesive agent caused no significant increases (p > 0.05) on the measured parameters. The ultra-high light-curing protocol significantly increased ΔT in composite compared to 10 s curing (p < 0.05).
SIGNIFICANCE
When the adhesive layer was photocured alone in a cavity, with a 2 mm thick dentin floor, the exothermal release of energy resulted in higher temperatures with a 10 s curing protocol, compared to a 3 s high irradiance. But when subsequently photocuring a 2 mm layer of composite, the resultant temperatures generated at pulpal roof location from the two curing protocols were similar and therefore there was no increased hazard to the dental pulp from the immediately prior adhesive photopolymerization, cured via the ultra-high irradiation protocol.
Topics: Humans; Temperature; Thermography; Dental Cements; Composite Resins; Dental Caries; Materials Testing; Resin Cements; Dentin
PubMed: 38129192
DOI: 10.1016/j.dental.2023.12.006 -
BMC Oral Health May 2022To evaluate the effect of amalgam contamination, different surface treatments, and adhesive protocols on dentin microleakage to bulk-fill composite resin material.
BACKGROUND
To evaluate the effect of amalgam contamination, different surface treatments, and adhesive protocols on dentin microleakage to bulk-fill composite resin material.
METHODS
Forty teeth were fixed in (polyvinyl siloxane) PVS molds, and the Class II cavities were placed on mesial and distal aspects. Thirty teeth were restored by amalgam and thermocycled to 10,000 cycles (5 and 55 °C, 30-s dwell time). The rest were restored with Filtek one Bulk Fill composite without amalgam predecessor. Samples were divided into: G1 (dentin pretreated with 2% chlorhexidine gluconate), G2 (0.5 mm of dentin was removed), G3 (no surface modification), and G4 (control, where composite was bonded to sound dentin without amalgam predecessor.). Single Bond Universal Adhesive system was used to bond the composite material, by using the etch-and-rinse protocol in the mesial cavity preparation and self-etch protocol in the distal. Specimens underwent thermocycling for 5000 cycles, then embedded in silver nitrate and sectioned for stereomicroscope examination. Descriptive statistics, Mann-Whitney U test, and Kruskal-Wallis test were used to analyze the results at p < 0.05.
RESULTS
The highest microleakage score values (4.00) were found in the G2, and G4 in etch-and-rinse protocol. While the lowest scores were found in G2 when using self-etching protocol (1.5). Lower microleakage values were associated with the chlorhexidine treatment group for both adhesive protocols. No significant differences were found between amalgam contaminated and non-contaminated groups.
CONCLUSIONS
Amalgam contamination did not affect microleakage. Self-etching adhesive protocol significantly reduced microleakage for all groups irrespective of the surface treatment. Chlorhexidine pretreatment improved microleakage for both adhesive protocols but had no significant effect.
Topics: Chlorhexidine; Composite Resins; Dental Cavity Preparation; Dental Cements; Dental Leakage; Dental Restoration, Permanent; Dentin; Dentin-Bonding Agents; Humans; Materials Testing; Resin Cements
PubMed: 35585533
DOI: 10.1186/s12903-022-02214-1 -
Journal of the National Cancer Institute May 2020In the modern era of targeted and immune-based therapies, investigator and patient expectations of availability and efficacy in phase I trials have increased. We...
In the modern era of targeted and immune-based therapies, investigator and patient expectations of availability and efficacy in phase I trials have increased. We assessed availability of, and benefit from, early drug development trials, specifically in patients with gastrointestinal cancers. We reviewed computerized referral records of the Early Drug Development Service at our institution to identify patients internally referred from our Gastrointestinal Oncology Service in calendar year 2018. End points were treatment on a trial, 3- and 6-month progression-free survival (PFS), and any tumor shrinkage. Of 394 gastrointestinal cancer patients referred in 2018, 54 enrolled on a trial and 53 (13.5%) were treated (1 withdrew before treatment): 34 on immune-based and 19 on targeted (3 to phase II basket) studies. None of the 52 patients who had exhausted standard therapy achieved 6-month PFS, two (3.8%) met 3-month PFS with tumor growth below Response Evaluation Criteria in Solid Tumors progression at 3 months, and both came off study for progression at 4 months. One patient who was to receive an irinotecan-based regimen as standard therapy instead received irinotecan plus an investigational targeted agent and remained stable for 8 months. No patients achieved any degree of tumor shrinkage. The most common reasons for nonaccrual were lack of available protocol treatment openings and failure to meet eligibility criteria for specific trials. Thus, availability and benefit from investigational treatment in this treatment-refractory gastrointestinal cancer patient population was extremely modest. Expectations regarding both availability and efficacy of phase I investigational therapy in gastrointestinal cancer patients likely exceed what our experience suggests.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Clinical Trials, Phase I as Topic; Drugs, Investigational; Gastrointestinal Neoplasms; Health Services Accessibility; Humans
PubMed: 31834379
DOI: 10.1093/jnci/djz228 -
Saudi Journal of Biological Sciences Oct 2020Nanotechnology is evolving as a significant discipline of research with various applications. It includes the materials and their applications having one dimension in... (Review)
Review
Nanotechnology is evolving as a significant discipline of research with various applications. It includes the materials and their applications having one dimension in the range of 1-100 nm. Many chemical and physical protocol have been utilized for the nanoparticles (NPs) fabrication. These protocols are costly, hazardous and consumes high energy. Thus, researchers are inclined towards biological synthesis of NPs using plant and or herbal extract as these methods are simple, sustainable, ecofriendly and cost-effective. Flower is an important part of plants, and contained several phytochemicals such as flavonoids, terpenoids, coumarins, sterol and xanthones which acts as an important precursor for NPs synthesis. These compounds acted as reducing as well as stablishing agent during fabrication processes. They have been thoroughly characterized by various techniques. The fabricated NPs have shown potential antimicrobial activity against bacterial and fungal infections. They have been also used as potential therapeutic agent for human breast cancer, gastric adenocarcinoma cell, colorectal adenocarcinoma cell and pancreas ductal adenocarcinoma cells. Overall, the aim of this review article to facilitates the recent understanding of flower-mediated NPs fabrication (a sustainable and ecofriendly resource), their application in different disciplines and challenges.
PubMed: 32994711
DOI: 10.1016/j.sjbs.2020.05.012 -
Sensors (Basel, Switzerland) Jun 2022Recently, the Internet of Things (IoT) has emerged as an important way to connect diverse physical devices to the internet. The IoT paves the way for a slew of new...
Recently, the Internet of Things (IoT) has emerged as an important way to connect diverse physical devices to the internet. The IoT paves the way for a slew of new cutting-edge applications. Despite the prospective benefits and many security solutions offered in the literature, the security of IoT networks remains a critical concern, considering the massive amount of data generated and transmitted. The resource-constrained, mobile, and heterogeneous nature of the IoT makes it increasingly challenging to preserve security in routing protocols, such as the routing protocol for low-power and lossy networks (RPL). RPL does not offer good protection against routing attacks, such as rank, Sybil, and sinkhole attacks. Therefore, to augment the security of RPL, this article proposes the energy-efficient multi-mobile agent-based trust framework for RPL (MMTM-RPL). The goal of MMTM-RPL is to mitigate internal attacks in IoT-based wireless sensor networks using fog layer capabilities. MMTM-RPL mitigates rank, Sybil, and sinkhole attacks while minimizing energy and message overheads by 25-30% due to the use of mobile agents and dynamic itineraries. MMTM-RPL enhances the security of RPL and improves network lifetime (by 25-30% or more) and the detection rate (by 10% or more) compared to state-of-the-art approaches, namely, DCTM-RPL, RBAM-IoT, RPL-MRC, and DSH-RPL.
Topics: Internet of Things; Prospective Studies; Trust
PubMed: 35746321
DOI: 10.3390/s22124539 -
Einstein (Sao Paulo, Brazil) 2020To describe antiretroviral treatment regimens prescribed and their compliance with the Clinical Protocol and Therapy Guidelines of the Ministry of Health for the... (Observational Study)
Observational Study
OBJECTIVE
To describe antiretroviral treatment regimens prescribed and their compliance with the Clinical Protocol and Therapy Guidelines of the Ministry of Health for the management of HIV infection.
METHODS
Observational and descriptive study. Secondary data of the state of Paraná (Brazil) on drugs, treatment regimens, lines of treatment and number of individuals on treatment, from January to June 2018, were accessed at the Antiretroviral Agents Logistic Control System. Combinations of antiretroviral drugs (treatment regimens) were compared according to the current Clinical Protocol and Therapy Guidelines and non-compliances were classified and quantified.
RESULTS
In Paraná, 35,127 individuals with HIV were treated with 253 different treatment regimens. Of the prescribed regimens, 19.1% were first-line, 27.4% second-line and 48.5% third-line. Among non-compliances, the most prevalent were absence of association of protease inhibitors and ritonavir (42.8%), low efficacy triple therapy (36.9%), double therapy (26.1%), monotherapy (20.3%), and triple therapy of nucleoside analog reverse transcriptase inhibitors (17.1%).
CONCLUSION
Most individuals receiving HIV treatment in the state of Paraná are on treatment regimens established in the current Clinical Protocol and Therapy Guidelines, which contributes to successful therapy. However, associations not provided by the current Clinical Protocol and Therapy Guidelines were identified in the initial treatment lines, which could lead to ineffectiveness, virologic failure and viral resistance.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; Brazil; Clinical Protocols; Drug Therapy, Combination; Guideline Adherence; HIV Infections; Humans; Medication Adherence
PubMed: 32074221
DOI: 10.31744/einstein_journal/2020AO4995 -
Critical Care Explorations Mar 2021The recent conflicting data on the mortality benefit of neuromuscular blocking agents in acute respiratory distress syndrome and the potential adverse effects of...
OBJECTIVES
The recent conflicting data on the mortality benefit of neuromuscular blocking agents in acute respiratory distress syndrome and the potential adverse effects of continuous neuromuscular blocking agent necessitates that these medications should be used judiciously with dose reduction in mind. The aims of the study were to improve the process of care by provider education of neuromuscular blocking agent titration and monitoring and to determine the impact of clinical endpoint based neuromuscular blocking agent titration protocol.
DESIGN
We conducted a proof-of-concept historically controlled study of protocol-based intervention standardizing paralytic monitoring and titration using clinical variables. Education of the protocol was provided to ICU staff via bedside teaching and workshops. The primary outcomes were the time to reach goal paralysis and cumulative neuromuscular blocking agent dose. Secondary outcomes included maintenance of deeper sedation (Richmond Agitation and Sedation Scale -5) prior to neuromuscular blocking agent initiation, total time on mechanical ventilation, length of stay, and mortality.
SETTING
Medical ICU at a quaternary academic hospital between March 2019 and June 2020.
PATIENTS
Adult severe acute respiratory distress syndrome (Pao/Fio <150) patients requiring neuromuscular blocking agent for greater than or equal to 12 hours. Eighty-two patients fulfilled inclusion criteria, 46 in the control group and 36 in the intervention group.
INTERVENTIONS
Education and implementation of standardized protocol.
MEASUREMENTS AND MAIN RESULTS
Compared with the control group, the time to reach goal paralysis in the intervention group was shorter (8.55 ± 9.4 vs 2.63 ± 5.9 hr; < 0.0001) on significantly lower dose of cisatracurium (total dose 1,897.96 ± 1,241.0 vs 562.72 ± 546.7 mg; < 0.0001 and the rate 5.84 ± 2.66 vs 1.99 ± 0.95 µg/kg/min; < 0.0001). Deeper sedation was achieved at the time of initiation of neuromuscular blocking agent in the intervention arm (mean Richmond Agitation and Sedation Scale -3.3 ± 1.9 vs -4.3 ± 1.7; = 0.015). There was no significant difference in total time on mechanical ventilation, length of ICU stay, length of hospital stay, and mortality between the two groups.
CONCLUSIONS
Implementation of comprehensive education, standardization of sedation prior to neuromuscular blocking agent initiation, integration of clinical variables in determining paralysis achievement, and proper use of peripheral nerve stimulation served as optimal strategies for the titration and monitoring of neuromuscular blocking agent in acute respiratory distress syndrome. This reduced drug utilization while continuing to achieve benefit without causing adverse effects.
PubMed: 33786447
DOI: 10.1097/CCE.0000000000000371 -
Toxicology Reports 2022Kambo is the name of a natural substance derived from the glandular secretions of the amphibian , a species native to regions in South America. The communities living in... (Review)
Review
Kambo is the name of a natural substance derived from the glandular secretions of the amphibian , a species native to regions in South America. The communities living in these areas administer the substance generally transdermally during rituals for religious-purifying purposes, producing small skin burns. The scientific literature has reported some cases of intoxication following the use of Kambo but this aspect is still poorly understood. In fact, no shared therapy protocols exist for these events nor any real legislation on Kambo. The purpose of this work was to examine all cases of acute intoxication resulting from the administration of Kambo and published over the last 10 years, illustrating clinical signs, laboratory findings, instrumental tests, and therapy. The several cases identified in our review confirm that acute Kambo intoxication can occur, with serious and life-threatening effects. We developed a protocol aimed at the early diagnosis of cases of suspected acute intoxication by creating a treatment algorithm. The study aims to investigate the pathophysiology of these events in humans, proposing a protocol for the diagnosis and treatment of these cases that can be used by healthcare professionals.
PubMed: 35515815
DOI: 10.1016/j.toxrep.2022.04.005 -
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