Faculty members as academic knowledge brokers in Iran's health sector: a social network analysis study.

BACKGROUND: Interaction between researchers and policymakers is an essential factor to facilitate the evidence-informed policymaking. One of the effective ways to establish this relationship and promote evidence-informed policymaking is to employ people or organizations that can play the role of knowledge brokers. This study aims to analyze the communication network and interactions between researchers and policymakers in Iran's health sector and identify key people serving as academic knowledge brokers. METHODS: This study was a survey research. Using a census approach, we administered a sociometric survey to faculty members in the health field in top ten Iranian medical universities to construct academic-policymaker network using social network analysis method. Network maps were generated using UCINET and NetDraw software. We used Indegree Centrality, Outdegree Centrality, and Betweenness Centrality indicators to determine knowledge brokers in the network. RESULTS: The drawn network had a total of 188 nodes consisting of 94 university faculty members and 94 policymakers at three national, provincial, and university levels. The network comprised a total of 177 links, with 125 connecting to policymakers and 52 to peers. Of 56 faculty members, we identified four knowledge brokers. Six policymakers were identified as key policymakers in the network, too. CONCLUSIONS: It seems that the flow of knowledge produced by research in the health field in Iran is not accomplished well from the producers of research evidence to the users of knowledge. Therefore, it seems necessary to consider incentive and support mechanisms to strengthen the interaction between researchers and policymakers in Iran's health sector.

Exploring the OTITIS Research Landscape Through a Scientometric Approach.

Otitis media is a common health problem affecting people of all ages and significantly impacting public health and healthcare costs. Otitis media, a type of middle ear disease, is one of the most common types. This scientometric study aimed to provide an overview of the knowledge domain in otitis media research. Documents were retrieved from the Web of Science database. A scientometric study was then performed on a sample of 27,213 documents. This study found that research on otitis media has increased significantly in recent years, with an annual growth rate of 4.58%. The average age of the documents analyzed was 18 years, with an average of 21.88 citations and an average of 4.58 authors. The United States, the United Kingdom, and Japan ranked first to third in terms of number of publications. Still, the United States, China, and Sweden were in a better position in terms of impact on the research network. Co-occurrence word analysis showed that significant attention was given to topics such as chronic inflammation in autism, acute inflammation in otitis media, and increased fluid in the middle ear. This study highlights the need to prioritize and focus attention on otitis, particularly otitis media, due to its prevalence and impact on public health. The use of scientometric software, such as Biblioshiny and CiteSpace, provides a valuable means of assessing research trends and identifying important areas for future study in the field of knowledge.

Single agent subcutaneous blinatumomab for advanced acute lymphoblastic leukemia.

Blinatumomab is a BiTE® (bispecific T-cell engager) molecule that redirects CD3+ T-cells to engage and lyse CD19+ target cells. Here we demonstrate that subcutaneous (SC) blinatumomab can provide high efficacy and greater convenience of administration. In the expansion phase of a multi-institutional phase 1b trial (ClinicalTrials.gov, NCT04521231), heavily pretreated adults with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) received SC blinatumomab at two doses: (1) 250 µg once daily (QD) for week 1 and 500 µg three times weekly (TIW) thereafter (250 µg/500 µg) or (2) 500 µg QD for week 1 and 1000 µg TIW thereafter (500 µg/1000 µg). The primary endpoint was complete remission/complete remission with partial hematologic recovery (CR/CRh) within two cycles. At the data cutoff of September 15, 2023, 29 patients were treated: 14 at the 250 µg/500 µg dose and 13 at 500 µg/1000 µg dose. Data from two ineligible patients were excluded. At the end of two cycles, 12 of 14 patients (85.7%) from the 250 µg/500 µg dose achieved CR/CRh of which nine patients (75.0%) were negative for measurable residual disease (MRD; <10-4 leukemic blasts). At the 500 µg/1000 µg dose, 12 of 13 patients (92.3%) achieved CR/CRh; all 12 patients (100.0%) were MRD-negative. No treatment-related grade 4 cytokine release syndrome (CRS) or neurologic events (NEs) were reported. SC injections were well tolerated and all treatment-related grade 3 CRS and NEs responded to standard-of-care management, interruption, or discontinuation. Treatment with SC blinatumomab resulted in high efficacy, with high MRD-negativity rates and acceptable safety profile in heavily pretreated adults with R/R B-ALL.

Visualization of the field of knowledge in sexual violence: a scientometric analysis based on citespace.

BACKGROUND: Sexual violence (SV) is a serious public health problem affecting millions of people each year. The main aim of this article is to provide a large-scale snapshot of the field of knowledge in SV research using a scientometric approach. METHODS: Documents were retrieved from the Web of Science database. Then, a scientometric study was carried out on a sample of 65,610 documents. Co-citation and co-occurrence measures have been calculated and related networks have been drawn using Citespace and Biblioshiny software. RESULTS: The main findings indicate that research in SV has increased significantly in recent years. On the other hand, the publication of about one-third of these documents by a single author is due to the special nature of this topic and its taboo in many societies. In addition, a large number of multimedia documents demonstrate the role and importance of multimedia resources in SV studies. Despite the attention to SV research by poor or developing countries to research in the field of SV, 95% of the documents have been published by 20 developed countries. Additionally, the general research approach has changed from criminology to psychology. CONCLUSIONS: Therefore, it seems that the discussion of psychological disorders in the occurrence of sexual violence reveals a new approach to SV. The concepts related to SV have been linked to broader areas than in the past. This, along with emphasizing prevention topics in the long term, will increase awareness of SV and reduce the possibility of abuse of vulnerable people.

A phase 1, first-in-child, multicenter study to evaluate the safety and efficacy of the oncolytic herpes virus talimogene laherparepvec in pediatric patients with advanced solid tumors.

Background: The survival rates for pediatric patients with relapsed and refractory tumors are poor. Successful treatment strategies are currently lacking and there remains an unmet need for novel therapies for these patients. We report here the results of a phase 1 study of talimogene laherparepvec (T-VEC) and explore the safety of this oncolytic immunotherapy for the treatment of pediatric patients with advanced non-central nervous system tumors. Methods: T-VEC was delivered by intralesional injection at 106 plaque-forming units (PFU)/ml on the first day, followed by 108 PFU/ml on the first day of week 4 and every 2 weeks thereafter. The primary objective was to evaluate the safety and tolerability as assessed by the incidence of dose-limiting toxicities (DLTs). Secondary objectives included efficacy indicated by response and survival per modified immune-related response criteria simulating the Response Evaluation Criteria in Solid Tumors (irRC-RECIST). Results: Fifteen patients were enrolled into two cohorts based on age: cohort A1 (n = 13) 12 to ≤21 years old (soft-tissue sarcoma, n = 7; bone sarcoma, n = 3; neuroblastoma, n = 1; nasopharyngeal carcinoma, n = 1; and melanoma, n = 1) and cohort B1 (n = 2) 2 to <12 years old (melanoma, n = 2). Overall, patients received treatment for a median (range) of 5.1 (0.1, 39.4) weeks. No DLTs were observed during the evaluation period. All patients experienced at least one treatment-emergent adverse event (TEAE), and 53.3% of patients reported grade ≥3 TEAEs. Overall, 86.7% of patients reported treatment-related TEAEs. No complete or partial responses were observed, and three patients (20%) overall exhibited stable disease as the best response. Conclusions: T-VEC was tolerable as assessed by the observation of no DLTs. The safety data were consistent with the patients' underlying cancer and the known safety profile of T-VEC from studies in the adult population. No objective responses were observed. Trial Registration: ClinicalTrials.gov: NCT02756845. https://clinicaltrials.gov/ct2/show/NCT02756845.

A scientometric approach to psychological research during the COVID-19 pandemic.

During the COVID-19 pandemic, modern science demonstrated its ability to respond well to the health crisis by publishing useful and reliable information. This disease has also led to an increase in psychological publications in this field. However, most scientometric studies have focused on medical aspects, and social science research has been neglected. Therefore, to fill this research gap, we analyzed the research on COVID-19 in the field of psychology to provide an insight into the perspective, research fields, and international collaborations. Data were collected from the Web of Science database and analyzed using Citespace and Bibliometrix (Biblioshiny). The overall performance of the documents was described, and then keyword co-occurrence and co-authorship networks were visualized. Fifteen main clusters were formed by drawing document co-citation network. The result indicates that Anxiety, mental health, delirium, loneliness, and suicide were important topics for researchers. Considering the special conditions that COVID-19 created for human societies, perhaps one of the most important subjects in the field of health is psychological studies. Using the results of this study, psychology researchers can identify their potential colleagues and research gaps in the subject of Covid-19.

Evaluation of the bisphenol released in the saliva after residual adhesive removal in orthodontic patients by using ultrasonic scaling and rotary system: A single-center randomized clinical trial.

INTRODUCTION: Bisphenol A (BPA) is a substance commonly used in dental materials with noxious properties. Monomers of this substance may be dissolved in the saliva and cause adverse effects. This study aimed to evaluate the amount of BPA released in the saliva after residual adhesive removal in orthodontic patients using an ultrasonic scaler (US) and tungsten carbide bur (TCB). METHODS: This single-center randomized clinical trial was conducted on 40 subjects whose stainless-steel brackets were bonded directly with light-cured bonding and composite. The subjects were randomly divided into 2 equal groups (n = 20) of TCB or US according to the adhesive removal method. The salivary BPA level was determined using high-performance liquid chromatography-mass spectrometry. And adhesive cleaning time was measured by a stopwatch. Data were analyzed by SPSS using an independent t test and paired-samples t test (P <0.05). RESULTS: The mean salivary BPA level was significantly lower in the TCB method than in the US method. (1.008 ± 0.061 µg/mL and 2.83 ± 0.24 µg/mL, respectively) (P <0.001). The mean adhesive cleanup time was significantly shorter in the TCB method than in the US method (8.86 ± 0.83 minutes and 13.20±1.02 minutes, respectively) (P <0.001). CONCLUSIONS: According to the results, residual adhesive removal with TCB released less BPA in saliva and shortened the adhesive cleaning time than the US method. TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials (IRCT20200702047988N1). PROTOCOL: The protocol was not published before trial commencement.

Strategies, facilitators, and barriers to interaction between health researchers and policy makers: Protocol for a systematic review.

This systematic review protocol is developed with the objective to identify the strategies, facilitators, and barriers to interaction between researchers and policy makers to use research evidence in health policy making. It seems that review of interactive methods between researchers and policy makers can help to understand the role of researchers on evidence-informed policy making. Moreover, identifying barriers and facilitators of these interactions can help universities and institutions associated to health policy making in planning to improve the interaction between researchers and policy makers to facilitate evidence-informed policy making.

Functional in-vitro evaluation of the non-specific effects of BCG vaccination in a randomised controlled clinical study.

Bacille Calmette-Guérin (BCG), the only currently licenced tuberculosis vaccine, may exert beneficial non-specific effects (NSE) in reducing infant mortality. We conducted a randomised controlled clinical study in healthy UK adults to evaluate potential NSE using functional in-vitro growth inhibition assays (GIAs) as a surrogate of protection from four bacteria implicated in infant mortality. Volunteers were randomised to receive BCG intradermally (n = 27) or to be unvaccinated (n = 8) and were followed up for 84 days; laboratory staff were blinded until completion of the final visit. Using GIAs based on peripheral blood mononuclear cells, we observed a significant reduction in the growth of the Gram-negative bacteria Escherichia coli and Klebsiella pneumonia following BCG vaccination, but no effect for the Gram-positive bacteria Staphylococcus aureus and Streptococcus agalactiae. There was a modest association between S. aureus nasal carriage and growth of S. aureus in the GIA. Our findings support a causal link between BCG vaccination and improved ability to control growth of heterologous bacteria. Unbiased assays such as GIAs are potentially useful tools for the assessment of non-specific as well as specific effects of TB vaccines. This study was funded by the Bill and Melinda Gates Foundation and registered with ClinicalTrials.gov (NCT02380508, 05/03/2015; completed).

A review of neuroradiological abnormalities in patients with coronavirus disease 2019 (COVID-19).

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to various neurological manifestations. There is an urgent need for a summary of neuroimaging findings to accelerate diagnosis and treatment plans. We reviewed prospective and retrospective studies to classify neurological abnormalities observed in patients with the SARS-CoV-2 infection. METHODS: The relevant studies published in Scopus, PubMed and Clarivate Analytics databases were analysed. The search was performed for full-text articles published from 23 January 2020 to 23 February 2021. RESULTS: In 23 studies the number of patients with SARS-CoV-2 infection was 20,850 and the number of patients with neurological manifestations was 1996 (9.5%). The total number of patients with neuroradiological abnormalities was 602 (2.8%). SARS-CoV-2 has led to various neuroimaging abnormalities which can be categorised by neuroanatomical localisation of lesions and their main probable underlying pathogenesis. Cranial nerve and spinal root abnormalities were cranial neuritis and polyradiculitis. Parenchymal abnormalities fell into four groups of: (a) thrombosis disorders, namely ischaemic stroke and sinus venous thrombosis; (b) endothelial dysfunction and damage disorders manifested as various types of intracranial haemorrhage and posterior reversible encephalopathy syndrome; (c) hypoxia/hypoperfusion disorders of leukoencephalopathy and watershed infarction; and (d) inflammatory disorders encompassing demyelinating disorders, encephalitis, vasculitis-like disorders, vasculopathy and cytotoxic lesions of the corpus callosum. Leptomeninges disorders included meningitis. Ischaemic stroke was the most frequent abnormality in these studies. CONCLUSION: The review study suggests that an anatomical approach to the classification of heterogeneous neuroimaging findings in patients with SARS-CoV-2 and neurological manifestations would lend itself well for use by practitioners in diagnosis and treatment planning.

Design and preparation of a new multi-targeted drug delivery system using multifunctional nanoparticles for co-delivery of siRNA and paclitaxel.

Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel (PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid (FA) and glucose (Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCo-polyethyleneimine (FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol (PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu (NPsB) and FeCo-PEI-PLA-PEG-FA/Glu (NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX. Also, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.

Mucin-1 conjugated polyamidoamine-based nanoparticles for image-guided delivery of gefitinib to breast cancer.

PAMAM dendrimers (PAMs) are a group of polymeric macromolecules with distinctive physicochemical features, which can make them multifunctional theranostic nanoparticles (NPs). This study was designed to examine the impact of mucin-1 aptamer-conjugated NPs which were engineered using PAM for image-guided delivery of gefitinib (GEF) in the breast cancer cells/tumor. For this, PAMAM was conjugated with diethylenetriaminepentaacetic acid (DTPA) and modified with PEG2000 to prepare a multi-functionalized NPs. Subsequently, GEF was loaded onto the DTPA-PAM-PEG NPs, which were then armed with MUC-1 aptamer to form the DTPA-PAM-PEG/GEF@MUC-1 nanosystem. Finally, aptamer-conjugated NPs were radiolabeled by gallium-67 as an imaging agent to construct image-guided nanoplatforms. The prepared NPs were characterized by different techniques. The kinetic release models of gefitinib from radiolabeled NPs offer the sustained-release mechanism of the encapsulated drug for over 7 days. In vitro evaluation showed higher cytotoxicity and enhanced uptake of the mucin-grafted NPs in MCF-7 cells. Nuclear medicine imaging and in vivo investigations revealed significant accumulation of 67Ga-DTPA-PAM-PEG/GEF@MUC-1 in the tumor site of the animal models. These data suggest that the engineered NPs are a promising image-guided nanosystem for mucin-expressing breast cells/tumors with the assistance of nuclear medicine.

A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults.

BACKGROUND: This phase I trial evaluated the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, previously demonstrated to be protective in animal studies, in healthy UK adults. METHODS: We enrolled 42 healthy, BCG-vaccinated adults into 4 groups: low dose Starter Group (n = 6; ChAdOx1 85A alone), high dose groups; Group A (n = 12; ChAdOx1 85A), Group B (n = 12; ChAdOx1 85A prime - MVA85A boost) or Group C (n = 12; ChAdOx1 85A - ChAdOx1 85A prime - MVA85A boost). Safety was determined by collection of solicited and unsolicited vaccine-related adverse events (AEs). Immunogenicity was measured by antigen-specific ex-vivo IFN-γ ELISpot, IgG serum ELISA, and antigen-specific intracellular IFN-γ, TNF-α, IL-2 and IL-17. RESULTS: AEs were mostly mild/moderate, with no Serious Adverse Events. ChAdOx1 85A induced Ag85A-specific ELISpot and intracellular cytokine CD4+ and CD8+ T cell responses, which were not boosted by a second dose, but were boosted with MVA85A. Polyfunctional CD4+ T cells (IFN-γ, TNF-α and IL-2) and IFN-γ+, TNF-α+ CD8+ T cells were induced by ChAdOx1 85A and boosted by MVA85A. ChAdOx1 85A induced serum Ag85A IgG responses which were boosted by MVA85A. CONCLUSION: A ChAdOx1 85A prime - MVA85A boost is well tolerated and immunogenic in healthy UK adults.

Scientific misconduct and Iranian scientists / Mala conducta científica y científicos iraníes

No disponible

Alternate aerosol and systemic immunisation with a recombinant viral vector for tuberculosis, MVA85A: A phase I randomised controlled trial.

BACKGROUND: There is an urgent need for an effective tuberculosis (TB) vaccine. Heterologous prime-boost regimens induce potent cellular immunity. MVA85A is a candidate TB vaccine. This phase I clinical trial was designed to evaluate whether alternating aerosol and intradermal vaccination routes would boost cellular immunity to the Mycobacterium tuberculosis antigen 85A (Ag85A). METHODS AND FINDINGS: Between December 2013 and January 2016, 36 bacille Calmette-Guérin-vaccinated, healthy UK adults were randomised equally between 3 groups to receive 2 MVA85A vaccinations 1 month apart using either heterologous (Group 1, aerosol-intradermal; Group 2, intradermal-aerosol) or homologous (Group 3, intradermal-intradermal) immunisation. Bronchoscopy and bronchoalveolar lavage (BAL) were performed 7 days post-vaccination. Adverse events (AEs) and peripheral blood were collected for 6 months post-vaccination. The laboratory and bronchoscopy teams were blinded to treatment allocation. One participant was withdrawn and was replaced. Participants were aged 21-42 years, and 28/37 were female. In a per protocol analysis, aerosol delivery of MVA85A as a priming immunisation was well tolerated and highly immunogenic. Most AEs were mild local injection site reactions following intradermal vaccination. Transient systemic AEs occurred following vaccination by both routes and were most frequently mild. All respiratory AEs following primary aerosol MVA85A (Group 1) were mild. Boosting an intradermal MVA85A prime with an aerosolised MVA85A boost 1 month later (Group 2) resulted in transient moderate/severe respiratory and systemic AEs. There were no serious adverse events and no bronchoscopy-related complications. Only the intradermal-aerosol vaccination regimen (Group 2) resulted in modest, significant boosting of the cell-mediated immune response to Ag85A (p = 0.027; 95% CI: 28 to 630 spot forming cells per 1 × 106 peripheral blood mononuclear cells). All 3 regimens induced systemic cellular immune responses to the modified vaccinia virus Ankara (MVA) vector. Serum antibodies to Ag85A and MVA were only induced after intradermal vaccination. Aerosolised MVA85A induced significantly higher levels of Ag85A lung mucosal CD4+ and CD8+ T cell cytokines compared to intradermal vaccination. Boosting with aerosol-inhaled MVA85A enhanced the intradermal primed responses in Group 2. The magnitude of BAL MVA-specific CD4+ T cell responses was lower than the Ag85A-specific responses. A limitation of the study is that while the intradermal-aerosol regimen induced the most potent cellular Ag85A immune responses, we did not boost the last 3 participants in this group because of the AE profile. Timing of bronchoscopies aimed to capture peak mucosal response; however, peak responses may have occurred outside of this time frame. CONCLUSIONS: To our knowledge, this is the first human randomised clinical trial to explore heterologous prime-boost regimes using aerosol and systemic routes of administration of a virally vectored vaccine. In this trial, the aerosol prime-intradermal boost regime was well tolerated, but intradermal prime-aerosol boost resulted in transient but significant respiratory AEs. Aerosol vaccination induced potent cellular Ag85A-specific mucosal and systemic immune responses. Whilst the implications of inducing potent mucosal and systemic immunity for protection are unclear, these findings are of relevance for the development of aerosolised vaccines for TB and other respiratory and mucosal pathogens. TRIAL REGISTRATION: ClinicalTrials.gov NCT01954563.

Development of a non-human primate BCG infection model for the evaluation of candidate tuberculosis vaccines.

The lack of validated immunological correlates of protection makes tuberculosis vaccine development difficult and expensive. Using intradermal bacille Calmette-Guréin (BCG) as a surrogate for aerosol Mycobacterium tuberculosis (M.tb) in a controlled human infection model could facilitate vaccine development, but such a model requires preclinical validation. Non-human primates (NHPs) may provide the best model in which to do this. Cynomolgus and rhesus macaques were infected with BCG by intradermal injection. BCG was quantified from a skin biopsy of the infection site and from draining axillary lymph nodes, by culture on solid agar and quantitative polymerase chain reaction. BCG was detected up to 28 days post-infection, with higher amounts of BCG detected in lymph nodes after high dose compared to standard dose infection. Quantifying BCG from lymph nodes of cynomolgus macaques 14 days post-high dose infection showed a significant reduction in the amount of BCG detected in the BCG-vaccinated compared to BCG-naïve animals. Demonstrating a detectable vaccine effect in the lymph nodes of cynomolgus macaques, which is similar in magnitude to that seen in an aerosol M.tb infection model, provides support for proof-of-concept of an intradermal BCG infection model and evidence to support the further evaluation of a human BCG infection model.

Postoperative agitation in preschool children following emergence from sevoflurane or halothane anesthesia: a randomized study on the forestalling effect of midazolam premedication versus parental presence at induction of anesthesia.

OBJECTIVE: The effect of midazolam premedication on forestalling postoperative agitation in children is not yet concluded. The purpose of this study was to compare the effects of midazolam premedication and parental presence during anesthetic induction on the incidence of postoperative agitation in pediatric patients. METHODS: One hundred sixty-seven children between 2 years and 7 years of age, undergoing anesthesia for outpatient surgery, were enrolled and randomly divided into four groups: sevoflurane anesthesia with parental presence without premedication, sevoflurane anesthesia with oral midazolam premedication, halothane anesthesia with parental presence without premeditation, and halothane anesthesia with oral midazolam premedication. The children randomized to the premedication groups took oral midazolam 0.5mg/kg 20-30 minutes before anesthetic induction. For patients in the groups without premedication, one of the parents was present throughout the induction of anesthesia. One recovery room nurse blinded to the group assignment observed the patients and recorded the agitation scores all through their stay in the postanesthesia care unit. RESULTS: Postoperative agitation was significantly less in patients who received halothane anesthesia with oral midazolam premedication (p<0.002). CONCLUSION: Based on our data, the presence of a parent at induction of sevoflurance anesthesia was as effective as midazolam premedication in decreasing the incidence of postoperative agitation. Midazolam premedication, however, decreased postoperative agitation when halothane was used as the anesthetic agent.

Synthesis and hydrolytic behavior of ibuprofen prodrugs and their PEGylated derivatives.

Polyethylene glycol (PEG) derivatives of ibuprofen were prepared by esterification of PEG monosuccinate with hydroxy ethyl ester (HEE), hydroxy ethylamide (HEA), and hydroxy ethyl thioester (HET) of ibuprofen. Hydrolysis of HEE-PEG, HEA-PEG, and HET-PEG were studied in vitro with or without esterases to investigate the applicability of these PEGylated prodrugs. The polymeric prodrugs released major fraction of the parent drug (ibuprofen) and a small fraction of hydroxy ethyl derivatives after 48 hr. In HET-PEG, the amount of drug release was higher than HEE-PEG and HEA-PEG. The difference between acidic and alkali buffered solutions was considerable. In human plasma, 50% of drug was released after 150 hr incubation at 37 degrees C from HET-PEG.