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Archives de Pediatrie : Organe Officiel... Oct 2019Taste is a crucial factor that determines the palatability of the oral dosage form and patient compliance. (Review)
Review
UNLABELLED
Taste is a crucial factor that determines the palatability of the oral dosage form and patient compliance.
OBJECTIVE
The aim of this work was to evaluate the organoleptic excipients in oral antibiotics for pediatric use marketed in Brazil.
METHODS
The information was obtained from the GuidetoPharmacy, a reference for the pharmaceutical trade. The analysis included dosage forms for oral administration and drugs and their combination with antibacterial action. After this survey, we identified the constitution of the flavoring, sweetening, and coloring agents of each medicine. The results are presented in a descriptive form.
RESULTS
Twelve drugs or associations are distributed in 70medicines. Oral suspension was the most common pharmaceutical dosage form. Sweeteners were sucrose, sodium saccharin, and sodium cyclamate. All the coloring agents observed are synthetic and the most frequent ones were yellow twilight no. 6, yellow tartrazine no. 5, and red ponceau 4R. The presence of two or more types of flavorings per medicine was observed.
CONCLUSION
Antibacterials use coloring agents, flavorings, and sweeteners to facilitate the administration of medicines for children, using up to six different substances per formulation. No natural coloring agent was observed, demonstrating an issue to be explored in the future. It is important to note that, although necessary, these excipients are responsible for a high incidence of allergic reactions in children.
Topics: Administration, Oral; Anti-Bacterial Agents; Brazil; Child; Coloring Agents; Excipients; Flavoring Agents; Humans; Pediatrics; Sweetening Agents
PubMed: 31611144
DOI: 10.1016/j.arcped.2019.09.008 -
Frontiers in Immunology 2021We modified a Sabin Oral Poliovirus Vaccine (OPV) vector to permit secretion of the antigens of interest with the goal of improving anti-HIV Env humoral responses in a...
We modified a Sabin Oral Poliovirus Vaccine (OPV) vector to permit secretion of the antigens of interest with the goal of improving anti-HIV Env humoral responses in a SHIV mucosal immunization composed of DNA and recombinant OPVs. We evaluated stimulation of systemic and mucosal cell-mediated and humoral immunity in Rhesus macaques by two regimens, both involving a prime with a SHIVDNA construct producing non-infectious particles formulated in lipid nanoparticles, administered in the oral cavity, and two different viral vector boostings, administered in the oral cavity and intestinally.Group 1 was boosted with rMVA-SHIVBG505, expressing SIV Gag/Pol and HIV Env. Group 2 was boosted with a SHIV-OPV vaccine including a non-secreting SIVCA-p6-OPV, expressing Gag CA, NC and p6 proteins, and a HIVC1-V2-OPV, secreting the C1-V2 fragment of HIV Env, recognized by the broadly neutralizing antibody PG16. A time course analysis of anti-SHIV Gag and Env CD4+ and CD8+ T-cell responses in PBMC and in lymph node, rectal, and vaginal MNC was carried out. Both regimens stimulated significant cell-mediated responses in all compartments, with SHIV-OPV immunization stimulating more significant levels of responses than rMVA- SHIV. Boolean analysis of these responses revealed predominantly monofunctional responses with multifunctional responses also present in all tissues. Stimulation of antibody responses was disappointing in both groups with negative anti-SHIV IgG in plasma, and IgA in salivary, rectal and vaginal secretions being restricted to a few animals. After repeated rectal challenge with SHIV, two Group 1 animals remained uninfected at challenge termination. No significant differences were observed in post-infection viral loads between groups. After the acute phase decline, CD4+ T cell percentages returned to normal levels in vaccinated as well as control animals. However, when compared to controls, vaccinate groups had more significant preservation of PBMC and rectal MNC Th17/Treg ratios, considered the strongest surrogate marker of progression to AIDS. We conclude that the vaccine platforms used in this study are insufficient to stimulate significant humoral immunity at the tested doses and schedule but sufficient to stimulate significant mucosal and systemic cell-mediated immunity, impacting the preservation of key Th17 CD4+ T cells in blood and rectal mucosa.
Topics: Administration, Oral; Animals; Antibody Formation; HIV Antigens; Macaca mulatta; SAIDS Vaccines; Simian Acquired Immunodeficiency Syndrome; Vaccines, DNA; env Gene Products, Human Immunodeficiency Virus
PubMed: 34234789
DOI: 10.3389/fimmu.2021.702705 -
Nature Medicine Oct 2023The main barrier to HIV cure is a persistent reservoir of latently infected CD4 T cells harboring replication-competent provirus that fuels rebound viremia upon...
The main barrier to HIV cure is a persistent reservoir of latently infected CD4 T cells harboring replication-competent provirus that fuels rebound viremia upon antiretroviral therapy (ART) interruption. A leading approach to target this reservoir involves agents that reactivate latent HIV proviruses followed by direct clearance of cells expressing induced viral antigens by immune effector cells and immunotherapeutics. We previously showed that AZD5582, an antagonist of inhibitor of apoptosis proteins and mimetic of the second mitochondrial-derived activator of caspases (IAPi/SMACm), induces systemic reversal of HIV/SIV latency but with no reduction in size of the viral reservoir. In this study, we investigated the effects of AZD5582 in combination with four SIV Env-specific Rhesus monoclonal antibodies (RhmAbs) ± N-803 (an IL-15 superagonist) in SIV-infected, ART-suppressed rhesus macaques. Here we confirm the efficacy of AZD5582 in inducing SIV reactivation, demonstrate enhancement of latency reversal when AZD5582 is used in combination with N-803 and show a reduction in total and replication-competent SIV-DNA in lymph-node-derived CD4 T cells in macaques treated with AZD5582 + RhmAbs. Further exploration of this therapeutic approach may contribute to the goal of achieving an HIV cure.
Topics: Animals; HIV Infections; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Macaca mulatta; Anti-Retroviral Agents; Virus Latency; Virus Replication; HIV-1; Antibodies; Lymph Nodes; CD4-Positive T-Lymphocytes; Viral Load
PubMed: 37783968
DOI: 10.1038/s41591-023-02570-7 -
Annals of Emergency Medicine Sep 2021Thirty million pediatric visits (<18 years old) occur across 5,000 US emergency departments (EDs) each year, with most of these cases presenting to community EDs....
Thirty million pediatric visits (<18 years old) occur across 5,000 US emergency departments (EDs) each year, with most of these cases presenting to community EDs. Simulation-based training is an effective method to improve and sustain EDs' readiness to triage and stabilize critically ill infants and children, but large simulation centers are mostly concentrated at academic hospitals. The use of pediatric simulation-based training has been limited in the community ED setting due to the high cost of equipment and limited access to content experts in pediatric critical care. We designed an innovative "off-the-shelf" simulation-based training resource, "American College of Emergency Physicians (ACEP) SimBox," that provides a free low-technology manikin along with teaching aids and train-the-trainer materials to community EDs to run a simulation drill in their own workspaces with local educators. The goal was to develop an "off-the-shelf," free, open-access, simulation-based resource to improve the readiness of community EDs to triage, resuscitate, and transfer critically ill infants as measured by presimulation and postsimulation surveys measuring opinions regarding the scenario, session experience, and most valuable aspect of the session. Between January 2018 and December 2019, 179 ACEP SimBoxes were shipped across the United States, reaching 36 of 50 states. Facilitators and participants who completed the postsimulation survey evaluated the session as a valuable use of their time. All facilitator respondents reported that the low-technology manikins, paired with their institution-specific equipment, were sufficient for learning, thus reducing costs. All participant respondents reported an increased commitment to pediatric readiness for their ED after completing the simulation session. This innovation resulted in the implementation of a unique simulation-based training intervention across many community EDs in the United States. The ACEP SimBox innovation demonstrates that an easy to use and unique simulation-based training tool can be developed, distributed, and implemented across many community EDs in the United States to help improve community ED pediatric readiness.
Topics: Child; Child, Preschool; Consensus Development Conferences as Topic; Critical Illness; Curriculum; Diffusion of Innovation; Emergency Service, Hospital; Health Personnel; Humans; Infant; Manikins; Pediatrics; Program Development; Simulation Training
PubMed: 34154842
DOI: 10.1016/j.annemergmed.2021.03.040 -
Immunity Jul 2023Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5) can cure HIV, yet mechanisms remain speculative. To...
Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5) can cure HIV, yet mechanisms remain speculative. To define how alloHSCT mediates HIV cure, we performed MHC-matched alloHSCT in SIV, anti-retroviral therapy (ART)-suppressed Mauritian cynomolgus macaques (MCMs) and demonstrated that allogeneic immunity was the major driver of reservoir clearance, occurring first in peripheral blood, then peripheral lymph nodes, and finally in mesenteric lymph nodes draining the gastrointestinal tract. While allogeneic immunity could extirpate the latent viral reservoir and did so in two alloHSCT-recipient MCMs that remained aviremic >2.5 years after stopping ART, in other cases, it was insufficient without protection of engrafting cells afforded by CCR5-deficiency, as CCR5-tropic virus spread to donor CD4 T cells despite full ART suppression. These data demonstrate the individual contributions of allogeneic immunity and CCR5 deficiency to HIV cure and support defining targets of alloimmunity for curative strategies independent of HSCT.
Topics: Animals; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; HIV Infections; Macaca fascicularis; Hematopoietic Stem Cell Transplantation; Viral Load
PubMed: 37236188
DOI: 10.1016/j.immuni.2023.04.019 -
The Journal of the American Academy of... May 2020Fractures of the pelvis and acetabulum, although uncommon in the pediatric cohort, represent a range of injuries with similarities to those seen in the adult cohort but... (Review)
Review
Fractures of the pelvis and acetabulum, although uncommon in the pediatric cohort, represent a range of injuries with similarities to those seen in the adult cohort but with key differences that are important for the treating physician to be aware of to allow for systematic evaluation and management of these potentially life-threatening injuries. As the pediatric skeleton matures, changes in anatomy and physiology influence injury pattern, diagnosis, treatment, and complications. High-energy fractures of the pediatric pelvis are particularly concerning given the reported mortality rates ranging from 3.2% to 18%, with severe fracture patterns being associated with visceral injury in up to 60% of patients. The unique complexity of pediatric patients requires a multidisciplinary team to fully address their care. A systematic approach to the initial evaluation and diagnosis of pediatric patients with fractures of the acetabulum or pelvic ring aids in choosing between surgical and nonsurgical management of these fractures and avoiding complications unique to the maturing skeleton. We present such an approach to assist the practitioner who infrequently treats these uncommon injuries.
Topics: Acetabulum; Fracture Fixation, Internal; Fractures, Bone; Humans; Pediatrics; Pelvic Bones
PubMed: 31592796
DOI: 10.5435/JAAOS-D-19-00082 -
Pharmacological Research Jul 2021Genome wide association, epidemiological, and clinical studies have established high lipoprotein(a) [Lp(a)] as a causal risk factor for atherosclerotic cardiovascular... (Review)
Review
Genome wide association, epidemiological, and clinical studies have established high lipoprotein(a) [Lp(a)] as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Lp(a) is an apoB100 containing lipoprotein covalently bound to apolipoprotein(a) [apo(a)], a glycoprotein. Plasma Lp(a) levels are to a large extent determined by genetics. Its link to cardiovascular disease (CVD) may be driven by its pro-inflammatory effects, of which its association with oxidized phospholipids (oxPL) bound to Lp(a) is the most studied. Various inflammatory conditions, such as rheumatoid arthritis (RA), systemic lupus erythematosus, acquired immunodeficiency syndrome, and chronic renal failure are associated with high Lp(a) levels. In cases of RA, high Lp(a) levels are reversed by interleukin-6 receptor (IL-6R) blockade by tocilizumab, suggesting a potential role for IL-6 in regulating Lp(a) plasma levels. Elevated levels of IL-6 and IL-6R polymorphisms are associated with CVD. Therapies aimed at lowering apo(a) and thereby reducing plasma Lp(a) levels are in clinical trials. Their results will determine if reductions in apo(a) and Lp(a) decrease cardiovascular outcomes. As we enter this new arena of available treatments, there is a need to improve our understanding of mechanisms. This review will focus on the role of Lp(a) in inflammation and CVD.
Topics: Animals; Cardiovascular Diseases; Humans; Inflammation; Lipoprotein(a)
PubMed: 34033878
DOI: 10.1016/j.phrs.2021.105689 -
Antiviral Therapy Apr 2022The advent of antiretroviral combination therapy has significantly impacted the HIV/AIDS epidemic. No longer a death sentence, HIV infection can be controlled and... (Review)
Review
The advent of antiretroviral combination therapy has significantly impacted the HIV/AIDS epidemic. No longer a death sentence, HIV infection can be controlled and suppressed using cocktail therapies that contain two or more small molecule drugs. This review aims to highlight the discovery, development, and impact of one such molecule, namely, emtricitabine (FTC, emtriva), which is one of the most successful drugs in the fight against HIV/AIDS and has been taken by over 94% of individuals infected with HIV in the USA. We also pay tribute to Dr. John C. Martin, former CEO and Chairman of Gilead Sciences, who unexpectedly passed away in 2021. A true visionary, he was instrumental in delivering FTC, as part of combination therapy with TDF (tenofovir, viread) to the global stage. As the fight to eradicate HIV marches on, we honor Dr. Martin's legacy of collaboration, achievement, and hope.
Topics: Acquired Immunodeficiency Syndrome; Anti-HIV Agents; Emtricitabine; HIV Infections; HIV-1; Humans; Male; Tenofovir
PubMed: 35491570
DOI: 10.1177/13596535211067599 -
Health Expectations : An International... Jun 2022Better transparency of research results and participant engagement may help address poor participant accrual in paediatric clinical research. We conducted formative... (Review)
Review
INTRODUCTION
Better transparency of research results and participant engagement may help address poor participant accrual in paediatric clinical research. We conducted formative research to assess the acceptability of lay summaries and thank you notes, as well as to refine and expand guidance on participant and family engagement in Pediatric Trials Network's (PTN) pragmatic paediatric clinical research.
METHODS
Informed by draft PTN guidance, we conducted in-depth qualitative interviews with adolescent clinical trial participants and caregivers of paediatric participants in four trials conducted by PTN across eight sites. Participants were shown multiple versions of mock lay summaries and thank you notes and asked questions on their preferences for content and layout, and on trial communications. We used applied thematic analysis to analyse the data.
RESULTS
We interviewed 27 individuals engaged in PTN research: 24 caregivers and 3 adolescents. During a trial, participants want regular updates on study progress, reminders of the study purpose and reassurances of data confidentiality. After the trial, participants want to learn the aggregated results, particularly medication effectiveness. Participants reported that lay summaries should include a review of the study's purpose, methods and length, and that they expect to learn individual-level results. Participants stated that thank you notes must be of sufficient length to be meaningful.
CONCLUSIONS
This is the first study to describe stakeholder preferences for thank you note content and layout. Using these findings, we finalized PTN's trial communication guidance for use in future PTN trials. Research is needed to determine the effect of lay summaries and thank you notes on improving public transparency regarding clinical trials and paediatric trial recruitment and completion.
PATIENT OR PUBLIC CONTRIBUTION
By design, stakeholders (adolescent trial participants and caregivers of pediatric trial participants) contributed to PTN's guidance on the content and layout of lay summaries and thank you notes through their participation in the in-depth interviews.
Topics: Adolescent; Caregivers; Communication; Humans; Pragmatic Clinical Trials as Topic
PubMed: 35246906
DOI: 10.1111/hex.13448 -
Journal of Preventive Medicine and... Sep 2020HIV/AIDS remains a major public health concern globally and Health Care Workers (HCWs) are in the frontline of preventing and providing care in the health care system....
BACKGROUND
HIV/AIDS remains a major public health concern globally and Health Care Workers (HCWs) are in the frontline of preventing and providing care in the health care system. The aim of this study was to evaluate HIV/AIDS knowledge among Iranian HCWs.
METHODOLOGY
This cross-sectional study was conducted among 200 HCWs who were randomly selected from health care centers in Kermanshah city, west of Iran, 2018. HCWs filled out a self-administered questionnaire including the socio-demographic characteristics and HIV/AIDS knowledge items. Data were analyzed by SPSS version 16 using bivariate correlations, t-test, and ANOVA statistical tests.
RESULTS
The mean score of HIV/AIDS knowledge was 29.73 [95% CI: 28.79, 30.67], ranged from 0 to 40 (74.3% of total percent). There was no significant association and correlation between HIV/AIDS knowledge and sex, education level, marital status, age and job history. Up to 50% had inadequate knowledge about HIV/AIDS status and transmission in Iran.
CONCLUSIONS
HCWs HIV/AIDS knowledge was average and it seems need to be educating regarding HIV/AIDS status and transmission in Iran.
Topics: Acquired Immunodeficiency Syndrome; Adult; Cross-Sectional Studies; Female; HIV Infections; Health Knowledge, Attitudes, Practice; Health Personnel; Humans; Iran; Male; Middle Aged; Surveys and Questionnaires; Young Adult
PubMed: 33150227
DOI: 10.15167/2421-4248/jpmh2020.61.3.1474