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Journal of Research in Pharmacy Practice 2020Many contagious diseases, such as plague or cholera, played a role in changing the pathway of history. In this respect, although coronavirus was not as dangerous as... (Review)
Review
Many contagious diseases, such as plague or cholera, played a role in changing the pathway of history. In this respect, although coronavirus was not as dangerous as novel diseases such as swine flu and Ebola, the spread and the power of coronavirus infiltration caused public fear across the world. Three viruses among coronaviruses have been epidemic during the recent years, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 or new coronavirus. Respiratory droplets transmit the coronavirus through direct and indirect contact, and it can be transmitted through the contact in the case of remaining, the infected person's secretion on the surface. Based on the conducted studies on the treatment of COVID-19 disease, there is virtually no cure or vaccine for coronavirus infections yet. Those infected with Covid 19 are quarantined to prevent the outbreak of this disease. However, the researchers carried out different studies to investigate the impact of the various drugs on this virus, which in this study, we will examine the outline of this disease and the other conducted studies.
PubMed: 33912498
DOI: 10.4103/jrpp.JRPP_20_72 -
Journal of Acquired Immune Deficiency... Jun 2022To assess recent trends in the monitoring of antiretroviral therapy (ART) and detection of ART failure in adult and pediatric HIV clinics.
OBJECTIVE
To assess recent trends in the monitoring of antiretroviral therapy (ART) and detection of ART failure in adult and pediatric HIV clinics.
METHODS
We used data collected from 21 adult and 17 pediatric sites (across 13 and 6 countries/territories, respectively) in the International Epidemiology Databases to Evaluate AIDS - Asia-Pacific cohort. ART failure was defined as viral, immune, or clinical consistent with WHO guidelines.
RESULTS
A total of 8567 adults and 6149 children contributed data. Frequency of CD4 count monitoring declined between 2010 and 2019 among adult sites (from 1.93 to 1.06 tests/person per year, a 45.1% decline) and pediatric sites (from 2.16 to 0.86 testsperson per year, a 60.2% decline), whereas rates of viral load monitoring remained relatively stable. The proportion of adult and pediatric treatment failure detected as immune failure declined (from 73.4% to 50.0% and from 45.8% to 23.1%, respectively), whereas the proportion of failure detected as viral failure increased (from 7.8% to 25.0% and from 45.8% to 76.9%, respectively). The proportion of ART failure detected as clinical failure remained stable among adult and pediatric sites. The largest shifts in ART monitoring and failure type occurred in lower middle-income countries.
CONCLUSIONS
Although viral failure in our Asian cohort now comprises a larger portion of ART failure than in prior years, the diagnostic characteristics of immune and clinical failure, and recommendations on their management, remain important inclusions for regional ART guidelines.
Topics: Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Child; HIV Infections; Humans; Treatment Failure; Viral Load
PubMed: 35125475
DOI: 10.1097/QAI.0000000000002931 -
Pediatrics Jun 2023In 2015, CD4-based clinical staging criteria for antiretroviral therapy (ART) initiation were removed, expanding ART eligibility ("Treat All") for children, who shoulder...
OBJECTIVES
In 2015, CD4-based clinical staging criteria for antiretroviral therapy (ART) initiation were removed, expanding ART eligibility ("Treat All") for children, who shoulder an outsized burden of HIV-related deaths. To quantify the impact of "Treat All" on pediatric HIV outcomes, we examined shifts in pediatric ART coverage and AIDS mortality before and after "Treat All" implementation.
METHODS
We abstracted country-level ART coverage (proportion of children <15 years on ART) and AIDS mortality (deaths per 100 000 population) estimates over 11 years. For 91 countries, we also abstracted the year "Treat All" was incorporated into national guidelines. We used multivariable 2-way fixed effects negative binomial regression to estimate changes in pediatric ART coverage and AIDS mortality potentially attributable to "Treat All" expansion, reported as adjusted incidence rate ratios (adj.IRR) with 95% confidence intervals (95% CI).
RESULTS
From 2010 to 2020, pediatric ART coverage tripled (16% to 54%), and AIDS-related deaths were halved (240 000 to 99 000). Compared with the pre-implementation period, observed ART coverage continued increasing after "Treat All" adoption, but this rate of increase declined by 6% (adj.IRR = 0.94, 95% CI: 0.91-0.98). AIDS mortality continued declining after "Treat All" adoption, but this rate of decline decreased by 8% (adj.IRR = 1.08, 95% CI: 1.05-1.11) in the post-implementation period.
CONCLUSIONS
Although "Treat All" called for increased HIV treatment equity, ART coverage continues lagging in children and comprehensive approaches that address structural issues, including family-based services and intensified case-finding, are needed to close pediatric HIV treatment gaps.
Topics: Child; Humans; Acquired Immunodeficiency Syndrome; HIV Infections; Incidence; Eligibility Determination; Anti-HIV Agents
PubMed: 37194480
DOI: 10.1542/peds.2022-059013 -
Journal of Education & Teaching in... Oct 2020This classic team-based learning activity is specifically designed for emergency medicine bound medical students and junior residents; however, general pediatrics...
AUDIENCE
This classic team-based learning activity is specifically designed for emergency medicine bound medical students and junior residents; however, general pediatrics residents and general medical students may also benefit from this activity. Senior residents and fellows felt that the cases were too basic for them but enjoyed acting as facilitators.
INTRODUCTION/BACKGROUND
Vomiting is a common chief complaint in pediatric patients seen in the Emergency Department. 1-3 Presentations include acute, chronic, and cyclic vomiting, with underlying etiologies such as toxin injection, emotional disturbances, and movement disequilibrium. 1 By understanding these various pathways, it is helpful for physicians to distinguish between gastrointestinal and non-gastrointestinal causes of vomiting. 1 Most cases of vomiting in the pediatric population are self-limiting and require only supportive treatment; however, physicians must be able to recognize red flags associated with vomiting that warrant further evaluation. 1,3 This task may be challenging for medical students and residents in emergency medicine and those with infrequent exposure to pediatric patients. Therefore, this team-based learning activity was developed to help junior learners in differentiating non-emergent and emergent cases of pediatric vomiting. This activity aids learners in formulating a differential based on age, history, and characteristics of vomiting. We also review specific causes of pediatric vomiting that physicians cannot miss including intussusception, pyloric stenosis, malrotation, intestinal atresia, and intracranial pathology.
EDUCATIONAL OBJECTIVES
By the end of this TBL session, learners should be able to:Identify red flag symptoms that should prompt referral for urgent intervention by GI or surgical specialists.Recognize how chronicity of the vomiting can alter the differential diagnosisDescribe the varying pathways that can cause nausea and vomiting.Determine the necessity of imaging tests to confirm and possibly treat various causes of vomiting.Interpret imaging studies associated with specific causes of vomiting.
EDUCATIONAL METHODS
Classic Team Based Learning (cTBL).
RESEARCH METHODS
Learners and instructors provided verbal feedback after the session in a large group format. Learners were specifically asked if they felt the session was education, relevant, high-yield and level appropriate. One instructor provided written feedback to the cases as well.
RESULTS
Overall learners and instructors found the session to be engaging, informative and educational. Learners felt that the session was level appropriate for medical students and junior residents. As a result of feedback from the session, several of the iRAT/gRAT questions were adjusted and the group application cases were re-written and implemented.
DISCUSSION
Overall, the educational content and delivery was effective. This session was presented to a group of emergency medicine students, interns and residents. Learners were divided into smaller groups, and each group had a variety of level of learners, including pediatric emergency medicine fellows, present. The fellows, while not necessary to the delivery of the TBL, were extremely helpful in aiding the residents during the session. The final debriefing and answer review were essential to ensure that learners met all educational objectives and fully understood the materials.
TOPICS
Pediatric vomiting, intussusception, pyloric stenosis, intestinal atresia, malrotation, gastroesophageal reflux disease, superior mesenteric artery (SMA) syndrome, hyperemesis.
PubMed: 37465339
DOI: 10.21980/J8P363 -
Cells Feb 2023The evolution of antiretroviral therapies (ART) has tremendously improved the life expectancy of people living with human immunodeficiency virus (HIV) (PLWH), which is... (Review)
Review
The evolution of antiretroviral therapies (ART) has tremendously improved the life expectancy of people living with human immunodeficiency virus (HIV) (PLWH), which is currently similar to the general population. However, as PLWH are now living longer, they exhibit various comorbidities such as a higher risk of cardiovascular disease (CVD) and non-acquired immunodeficiency syndrome (AIDS)-defined malignancies. Clonal hematopoiesis (CH) is the acquisition of somatic mutations by the hematopoietic stem cells, rendering them survival and growth benefit, thus leading to their clonal dominance in the bone marrow. Recent epidemiologic studies have highlighted that PLWH have a higher prevalence of CH, which in turn is associated with increased CVD risk. Thus, a link between HIV infection and a higher risk for CVD might be explained through the induction of inflammatory signaling in the monocytes carrying CH mutations. Among the PLWH, CH is associated with an overall poorer control of HIV infection; an association that requires further mechanistic evaluation. Finally, CH is linked to an increased risk of progression to myeloid neoplasms including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), which are associated with particularly poor outcomes among patients with HIV infection. These bidirectional associations require further molecular-level understanding, highlighting the need for more preclinical and prospective clinical studies. This review summarizes the current literature on the association between CH and HIV infection.
Topics: Humans; Clonal Hematopoiesis; HIV Infections; HIV; Prospective Studies; Hematopoiesis; Leukemia, Myeloid, Acute; Cardiovascular Diseases
PubMed: 36899822
DOI: 10.3390/cells12050686 -
The Journal of Allergy and Clinical... Mar 2023Systemic autoinflammatory diseases (SAIDs) are caused by aberrant activation of 1 or more inflammatory pathways in an antigen-independent manner. Monogenic forms of... (Review)
Review
Systemic autoinflammatory diseases (SAIDs) are caused by aberrant activation of 1 or more inflammatory pathways in an antigen-independent manner. Monogenic forms of SAIDs typically manifest during childhood, and early treatment is essential to minimize morbidity and mortality. On the basis of the mechanism of disease and the dominant cytokine(s) that propagates inflammation, monogenic SAIDs can be grouped into major categories including inflammasomopathies/disorders of IL-1, interferonopathies, and disorders of nuclear factor-κB and/or aberrant TNF activity. This classification scheme has direct therapeutic relevance given the availability of biologic agents and small-molecule inhibitors that specifically target these pathways. Here, we review the experience of using biologics that target IL-1 and TNF as well as using Janus kinase inhibitors for the treatment of monogenic SAIDs in pediatric patients. We provide an evidence-based guide for the use of these medications and discuss their mechanism of action, safety profile, and strategies for therapeutic monitoring.
Topics: Animals; Humans; Child; Janus Kinase Inhibitors; Biological Products; Simian Acquired Immunodeficiency Syndrome; Cytokines; Hereditary Autoinflammatory Diseases; Interleukin-1
PubMed: 36707349
DOI: 10.1016/j.jaci.2022.12.816 -
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 -
Vaccine Jan 2020The potential advantages and unique challenges of the early life immune system for the development of HIV-specific broadly neutralizing antibodies were discussed during... (Review)
Review
The potential advantages and unique challenges of the early life immune system for the development of HIV-specific broadly neutralizing antibodies were discussed during a workshop entitled "Immunological Mechanisms of Inducing HIV Immunity in Infants" sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) in conjunction with the 2018 HIVR4P Conference held in Madrid, Spain. A safe and effective HIV vaccine remains a critical need in the fight against the HIV pandemic, especially to prevent emerging infections in infants, adolescents, and young adults. To successfully target these populations, a vaccine should ideally induce protective immune responses during childhood. Interestingly, several recent studies highlighting differences in immune responses between adults and children have suggested that the early life immune system could present advantages for the elicitation of broadly neutralizing antibodies (bnAbs), a response highly desired for an HIV vaccine. Notably, HIV-infected children develop bnAbs responses earlier and more frequently than infected adults; with emerging evidence that the pathways of elicitation of bnAb lineages may differ between adults and children. Moreover, there is precedent for the prevention of lifelong infections with pediatric immunization, and early life provides a unique window of opportunity for the administration of a multi-dose HIV vaccine that will likely be needed to achieve protective immunity. Further understanding of how the distinct early life immune system can be harnessed to trigger bnAb lineages for induction of durable and polyfunctional HIV-specific immunity is warranted. This strategy will include testing promising HIV vaccine candidates in pediatric populations in preclinical and clinical studies. Novel approaches to identify molecular markers of protection are also key to guide and accelerate pediatric HIV vaccine development.
Topics: AIDS Vaccines; Antibodies, Neutralizing; Education; HIV Antibodies; HIV Infections; HIV-1; Humans; Immunization; Infant; Infant, Newborn
PubMed: 31761501
DOI: 10.1016/j.vaccine.2019.11.011 -
Archives of Disease in Childhood Jan 2022Narcolepsy is a chronic disabling neurological sleep disorder that requires lifelong treatment. We have outlined the clinical features of narcolepsy, the assessment and... (Review)
Review
Narcolepsy is a chronic disabling neurological sleep disorder that requires lifelong treatment. We have outlined the clinical features of narcolepsy, the assessment and diagnosis process and have summarised the existing treatment options for children and adolescents with narcolepsy. In the future, the approach to management of paediatric narcolepsy should ideally be in a multidisciplinary setting, involving specialists in sleep medicine, sleep physiology, neurologists and psychologists/psychiatrists. A multidisciplinary approach will help to manage the potential impact of narcolepsy on children and adolescents who are in a stage of their life that is critical to their physical, emotional and social development and their academic attainment.
Topics: Actigraphy; Adolescent; Cataplexy; Central Nervous System Stimulants; Child; Exercise; Humans; Narcolepsy; Patient Care Team; Polysomnography; Sleep; Sleep Aids, Pharmaceutical; Wakefulness-Promoting Agents
PubMed: 33975822
DOI: 10.1136/archdischild-2020-320671