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1.
Hematology, Transfusion and Cell Therapy ; 44(Supplement 2):S343, 2022.
Article in English | EMBASE | ID: covidwho-2179139

ABSTRACT

Objetivos: Descrever dois casos clinicos de pacientes Portadores de Trombocitopenia Imune (PTI) cronica que apresentaram boa resposta terapeutica ao uso do Eltrombopag. Materiais e metodos: As informacoes foram obtidas atraves de revisao de prontuario eletronico. Relato de caso: Caso 1: Paciente 7 anos, diagnostico de PTI ha 1 ano e 4 meses, refratario a tratamento com corticoterapia e imunoglobulina. Iniciado Eltrombopag com dose primaria de 25 mg dia, sem resposta apos 1 mes, progredida dose para 50 mg dia com uma resposta plaquetaria apos 34 dias de 21000 U/mm3 para 169000 U/mm3, sem intercorrencias clinicas. Caso 2: Paciente 14 anos, PTI pos COVID, diagnosticado ha 1 ano e 11 meses, refratario a terapia com corticoide, imunoglobulina e azatioprina, iniciado Eltrombopag 50 mg dia com resposta plaquetaria apos 1 mes de 15000 para 401000 U/mm3, sem intercorrencias clinicas. Discussao: A trombocitopenia imune caracteriza-se por um processo imunomediado, onde ocorre a degradacao de plaquetas com contagem total menor 100,000U/mm3. e classificada como cronica quando o tempo de doenca ultrapassa 12 meses e pode trazer grande morbidade aos seus pacientes, nao so pelos sintomas e prejuizo na qualidade de vida, como pelos efeitos colaterais das terapias a longo prazo. o presente estudo relata 2 casos de trombocitopenia imune cronica em criancas, refrataria as terapias tradicionais, que apresentaram boa resposta terapeutica ao uso de Eltrombopag. O Eltrombopag e um agonista oral nao peptidico do receptor da trombopoietina que age estimulando a producao de plaquetas. Um estudo randomizado, multicentrico, controlado por placebo, PETIT 2, comprovou a eficacia e seguranca do uso do Eltrombopag na faixa etaria pediatrica, estabelecendo as doses iniciais de 25 a 50 mg/dia para pacientes de 6 a 17 anos, sendo sua dose maxima diaria recomendada de 75 mg. Nos estudos PETIT e PETIT 2, o tratamento com Eltrombopag demonstrou uma resposta plaquetaria satisfatoria, contagem de plaquetas de pelo menos 50,000U/mm3, entre 1 e 6 semanas de uso, sem necessidade de terapia de resgate. foram observados tambem uma reducao nos sangramentos e de medicacoes concomitantes. nao foram constatados eventos adversos graves, e os efeitos relativos a medicacao encontrados se relacionavam a alteacoes laboratoriais hepatobiliares, logo tendo seus parametros de normalidade restabelecidos apos descontinuacao do uso.resultados semelhantes tambem foram encontrados em um estudo observacional de centro unico realizado na china. Embora ainda haja poucos estudos sobre o uso do eltrombopag na faixa etaria pediatrica, estes tem apresentado resultados semelhantes aos encontrados em adultos, porem sem descricao de eventos tromboticos ou malignidade. Copyright © 2022

2.
Mol Med ; 28(1): 131, 2022 11 08.
Article in English | MEDLINE | ID: covidwho-2108708

ABSTRACT

BACKGROUND: Respiratory failure in severe coronavirus disease 2019 (COVID-19) is associated with a severe inflammatory response. Acetylcholine (ACh) reduces systemic inflammation in experimental bacterial and viral infections. Pyridostigmine increases the half-life of endogenous ACh, potentially reducing systemic inflammation. We aimed to determine if pyridostigmine decreases a composite outcome of invasive mechanical ventilation (IMV) and death in adult patients with severe COVID-19. METHODS: We performed a double-blinded, placebo-controlled, phase 2/3 randomized controlled trial of oral pyridostigmine (60 mg/day) or placebo as add-on therapy in adult patients admitted due to confirmed severe COVID-19 not requiring IMV at enrollment. The primary outcome was a composite of IMV or death by day 28. Secondary outcomes included reduction of inflammatory markers and circulating cytokines, and 90-day mortality. Adverse events (AEs) related to study treatment were documented and described. RESULTS: We recruited 188 participants (94 per group); 112 (59.6%) were men; the median (IQR) age was 52 (44-64) years. The study was terminated early due to a significant reduction in the primary outcome in the treatment arm and increased difficulty with recruitment. The primary outcome occurred in 22 (23.4%) participants in the placebo group vs. 11 (11.7%) in the pyridostigmine group (hazard ratio, 0.47, 95% confidence interval 0.24-0.9; P = 0.03). This effect was driven by a reduction in mortality (19 vs. 8 deaths, respectively). CONCLUSION: Our data indicate that adding pyridostigmine to standard care reduces mortality among patients hospitalized for severe COVID-19.


Subject(s)
COVID-19 , Adult , Male , Humans , Middle Aged , Female , COVID-19/drug therapy , Pyridostigmine Bromide/therapeutic use , SARS-CoV-2 , Respiration, Artificial , Inflammation , Treatment Outcome
3.
Archivos Venezolanos de Farmacologia y Terapeutica ; 40(9):946-952, 2021.
Article in English | EMBASE | ID: covidwho-2067022

ABSTRACT

The mortality rate estimated by the WHO worldwide for CO-VID-19 has been 5.7%, much higher than other communicable infectious diseases, so it is essential to apply a vaccine to the population to reduce the viral spread, according to the WHO there are 23 projects in clinical phase stage III, such as vaccines: ChadOx1, nCov-19, Gam-COVID-Vac, CoronaVac that show promising results in research published by The Lancet Infection Diseases journal, for which we consider correlating the three vaccines and determining which is safer, generates greater im-munogenicity and less reactogenicity in volunteer participants, for which we conducted a review bibliography and a meta-anal-ysis of high impact scientific articles, concluding that the three vaccines generate a rapid and intense immune response against SARS-CoV-2, neutralizing antibodies had elevated titers in participants at 28 days, who increased and remained stable with a second dose, although each of them have been tested in different numbers and populations, applying recombinant adenovi-ral vectors and chemically inactivated virions with adjuvant and placebo for which they are totally different but with the same purpose to generate memory antibodies against SARS-CoV-2. Copyright © 2021, Venezuelan Society of Pharmacology and Clinical and Therapeutic Pharmacology. All rights reserved.

4.
Pharmaceutical Journal ; 308(7961), 2022.
Article in English | EMBASE | ID: covidwho-2065042
5.
Pharmaceutical Journal ; 308(7959), 2022.
Article in English | EMBASE | ID: covidwho-2065023
6.
Otolaryngology - Head and Neck Surgery ; 167(1 Supplement):P147, 2022.
Article in English | EMBASE | ID: covidwho-2064494

ABSTRACT

Introduction: Olfactory dysfunction (OD) is a prevalent and characteristic symptom among individuals with COVID-19 infection. Although most patients with COVID-19-related OD experience a significant recovery, there exists a substantial population of patients with persistent OD with limited therapeutic options. Method(s): Patients with laboratory-confirmed or clinically suspected COVID-19 infection and self-reported new onset OD from March 2020 to October 2021 were prospectively recruited for a randomized, placebo-controlled, doubleblinded clinical trial. Patients with evidence of quantitative OD, defined as a Brief Smell Identification Test (BSIT) score of 9 or less, were eligible for study inclusion. The experimental group received 2 g of omega-3 fatty acid (O3FA) supplementation, including 1366-mg eicosapentaenoic acid and 504-mg docosahexaenoic acid, while the control group received an identical placebo, each to be taken daily for 6 weeks. The primary outcome was change in BSIT score from initial test to a 6-week follow-up BSIT. Result(s): A total of 117 patients were included in analysis, including 57 patients in the O3FA group and 60 in the placebo group. The mean duration of OD prior to study enrollment was 200.1 days with no significant difference between groups (P=.685). Patients receiving O3FA supplementation demonstrated a mean BSIT improvement of 1.12+/-1.99 compared with 0.68+/-0.86 in the placebo group (P=.385). Among those with severe hyposmia, defined as a BSIT score of 7 or less, patients in the O3FA group (n=23) demonstrated a BSIT improvement of 2.30+/-0.77 compared with 1.63+/-1.82 among those in the placebo group (n=16, P=.255). Conclusion(s): Our study showed a trend toward improved olfactory recovery among COVID-19-related OD patients receiving high doses of O3FA supplementation at a 6-week follow-up time point. Future work will be needed to better define the effectiveness and durability of O3FA supplementation as a treatment for COVID-19-related OD.

7.
Chest ; 162(4):A1003, 2022.
Article in English | EMBASE | ID: covidwho-2060748

ABSTRACT

SESSION TITLE: COVID-19 Co-Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Baricitinib with Remdesivir has been Food and Drug Administration (FDA) approved for hospitalized COVID-19 pneumonia patients requiring supplemental oxygen and is used across the United States. However, limited post-marketing surveillance data is currently available for these drugs. We present a case of an unvaccinated, immunocompetent patient with Herpes-Zoster virus (HZV) infection following baricitinib administration. CASE PRESENTATION: A 66-year-old African-American male with unknown vaccination status for Herpes zoster presented with worsening shortness of breath for 1 week. He had an SpO2 85% on presentation however had to be subsequently intubated due to worsening hypoxia in the ER. Cardiorespiratory exam was remarkable for diminished bibasilar breath sounds. Lab work was significant for positive COVID-19, elevated leukocytes and deranged inflammatory markers. CT chest showed bilateral ground glass opacities. He received a 14 day course of baricitinib, 10 days of dexamethasone and 5 days of remdesivir during his hospital stay. Tracheostomy and percutaneous endoscopic gastrostomy were performed due to prolonged vent dependence. On day 37 of hospitalization, the patient developed vesicular rashes over his left shoulder and anterior chest. Disseminated HZV infection was confirmed based on serologic testing. Patient received 7 days of valacyclovir with complete resolution. He was eventually discharged to a pulmonary rehabilitation center. DISCUSSION: Baricitinib was first developed for patients with rheumatoid arthritis and has been used in the treatment of rheumatoid arthritis and acts by reversible inhibition of JAK1 and JAK2. These proteins have been implicated in COVID-19 pathophysiology;promoting intracellular assembly of SARS-CoV-2 and subsequent cytokine release. Baricitinib in COVID-19 leads to the inhibition of proinflammatory cytokine release, antibody production, monocyte activation and viral proliferation. [1] There have been several studies published in support of Baricitinib induced HZV infection in rheumatoid arthritis patients, however there is little data available in COVID patients. Nonetheless, immunomodulatory action is the same. A study comparing the incidence rate (IR) of Baricitinib emergent HZV infection per 100 patient years (PY) vs placebo found IR/100PY 4.3 (p<_0.01) vs 3.1 (p not significant) [2]. Another study found the HZV IR vs placebo of 4.3 vs 1.0, with all-bari-RA IR was 3.2 (95% CI 2.8-3.7) [3]. In our case, the patient developed HZV infection after baricitinib treatment, demonstrating its immunomodulatory effects. CONCLUSIONS: This case demonstrates the ability of baricitinib to cause immunosuppression and hence causing HZV infection in COVID-19 affected patients. Reference #1: Schwartz DM, Bonelli M, Gadina M, O'shea JJ. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol. 2016;12(1):25. Reference #2: Kevin L, Masayoshi H, Mark C et al. Infections in baricitinib clinical trials for patients with active rheumatoid arthritis. Ann Rheum Dis.2020 Oct;79(10):1290-1297. Reference #3: Joseph S, Mark C, Tsutomu T et al. Safety profile of Baricitinib in patients with active rheumatoid arthritis with over 2 years median time in treatment. The Journal of Rheumatology January 2019, 46 (1) 7-18;DOI: https://doi.org/10.3899/jrheum.171361 DISCLOSURES: No relevant relationships by Mark Aloysius No relevant relationships by Gursharan Kaur No relevant relationships by Mohammed Musa Najmuddin No relevant relationships by mashu shrivastava

8.
Chest ; 162(4):A972, 2022.
Article in English | EMBASE | ID: covidwho-2060743

ABSTRACT

SESSION TITLE: Acute COVID-19 and Beyond: from Hospital to Homebound SESSION TYPE: Original Investigations PRESENTED ON: 10/18/2022 02:45 pm - 03:45 pm PURPOSE: To date, only dexamethasone, tocilizumab, and casirivimab/imdevimab have been shown to reduce mortality in COVID-19 patients. Baricitinib is a selective Janus kinase 1/2 inhibitor with known anti-inflammatory and anti-viral properties. We sought to perform a meta-analysis of RCTs assessing the role of baricitinib in hospitalized patients with COVID-19 disease. METHODS: Electronic databases such as MEDLINE, EMBASE, and Cochrane Central were searched till March 20, 2022, for randomized controlled trials evaluating the efficacy of baricitinib in hospitalized COVID-19 patients. The outcomes assessed were 28-day mortality, progression to respiratory failure needing positive pressure ventilation or death, progression to mechanical ventilation or ECMO, duration of hospitalization and time to discharge. RESULTS: Four studies (with 10,815 patients) were included in the analysis. In total, 5,477 patients received baricitinib, and 5,338 patients received standard care. Pooled analysis showed a significantly decreased risk of 28-day mortality (OR 0.85, 95% CI 0.76-0.96, p=0.006) and progression to invasive mechanical ventilation or ECMO (OR 0.80, 95% CI 0.69-0.94, p=0.005) in the baricitinib arm compared to standard therapy or placebo. In addition, there was a significant reduction in duration of hospitalization (MD -1.43, 95% CI -2.46, -0.40, p=0.007) and time to recovery (MD -0.88, 95% CI -1.34, -0.41, p=0.0002). CONCLUSIONS: Baricitinib improved the patient-centric outcomes of mortality and progression to severe disease i.e., need for invasive mechanical ventilation, in hospitalized patients with COVID-19 disease compared with standard therapy alone. CLINICAL IMPLICATIONS: Baricitinib may be used in conjunction with standard of care treatments to improve morbidity and mortality in hospitalized COVID-19 patients. DISCLOSURES: No relevant relationships by Gerardo Carino No relevant relationships by ARKADIY FINN No relevant relationships by Amos Lal No relevant relationships by VIJAIRAM SELVARAJ

9.
Chest ; 162(4):A430, 2022.
Article in English | EMBASE | ID: covidwho-2060595

ABSTRACT

SESSION TITLE: Issues After COVID-19 Vaccination Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Since the onset of the COVID-19 pandemic, vaccines were introduced to mitigate the spread of the virus. Depending on the COVID-19 vaccine, regimens consist of one dose (ie, J&J) or two doses (ie, Pfizer and Moderna) and is followed by a third dose/booster (for immunocompromised/immunocompetent individuals). Here, we present a case of COVID-19 infection in a triple vaccinated patient with concurrent rheumatoid arthritis (RA) receiving disease modifying antirheumatic drugs (DMARDs) who was unable to mount an adequate immune response to the vaccine. CASE PRESENTATION: Patient is a 67 year old male with PMH of RA (on DMARDs) presented to the ED with complaints of shortness of breath. He was on treatment for RA with leflunomide, rituximab and prednisone. He was COVID-19 triple vaccinated. In ED, the patient was found to be hypoxic, saturating at 87% on room air with a respiratory rate of 18. Physical examination was significant for coarse breath sounds bilaterally and remaining vitals were unremarkable. Patient was initially placed on 3 L oxygen via NC but due to persistent hypoxia, was transitioned to high-flow nasal cannula. Further investigations revealed that the patient was COVID-19 positive. He was treated with remdesivir and dexamethasone. His oxygen requirements continued to escalate and he was ultimately intubated. While in the ICU, the patient's hypoxia continued to worsen despite optimal medical and ventilatory management and he subsequently died. DISCUSSION: DMARDs are a group of medications used to slow the progression of rheumatoid arthritis. They work by reducing the immune response of B cells, T cells and cytokines. Our patient was on two commonly prescribed medications for rheumatoid arthritis, leflunomide and rituximab. The former acts by inhibiting the pyrimidine synthesis pathway, thereby decreasing T lymphocyte production and the latter depletes CD-20 positive B cells. While there is limited data on COVID-19 vaccine, it has been established that patients on DMARDs have reduced antibody titres after immunization against influenza and pneumonia vaccinations [1, 2]. A study assessing the effectiveness of a third vaccine dose in patients taking rituximab vs placebo found a significant difference in seroconversion (78.8% vs 18.2%, p=<0.0001) and neutralizing activity (80.0% vs 21.9%, p=<0.0001) [3]. In our case, the patient was on two immunosuppressive drugs which suppressed both the humoral and cell mediated immunity, resulting in an inadequate immune response and subsequently developing COVID. CONCLUSIONS: This case highlights patients on immunosuppressant therapy failing to mount an adequate immune response to the COVID-19 vaccine, warranting more booster doses in patients on DMARDs. Reference #1: Adler S, Krivine A, Weix J et al. Protective effect of A/ H1N1 vaccination in immune-mediated disease–a prospectively controlled vaccination study. Rheumatology 2012;51:695–700. Reference #2: Franca ILA, Ribeiro ACM, Aikawa NE et al. TNF blockers show distinct patterns of immune response to the pandemic influenza A H1N1 vaccine in inflammatory arthritis patients. Rheumatology 2012;51:2091–8. Reference #3: David S, Koray T, Filippo F et al. Efficacy and safety of SARS-CoV-2 revaccination in non-responders with immune-mediated inflammatory disease. http://dx.doi.org/10.1136/annrheumdis-2021-221554 DISCLOSURES: No relevant relationships by Gursharan Kaur No relevant relationships by Aishwarya Krishnaiah No relevant relationships by sandeep mandal

10.
Journal of Comprehensive Pediatrics ; 13(Supplement 1):9, 2022.
Article in English | EMBASE | ID: covidwho-2057839

ABSTRACT

Hazards' trade-off benefits should be considered. COVID is usually not severe in children/vs. the fact of high transmission esp. adolescence with high social communications. MISC in children may be severe. The new COVID-19 variants spread more quickly and cause more severe diseases. Millions of doses of the COVID-19 vaccine have been given, and there have only been 1,000 cases of heart inflammation. CDC: Notes that for every million doses given, there have been 67 cases of heart inflammation in boys 12 to 17 (nine in girls of that age group), 56 in those aged 18 to 24 (six in girls), and 20 in males 25 to 29 (three in girls). That means the risk is relatively low. COVID-19 can affect the heart, too - not only as part of MIS-C, a multisystem inflammatory complication of COVID-19 seen in children but also just from the infection itself. COVID-19 can cause heart damage, including myocarditis. Our only way out of this pandemic is to get as many people vaccinated as possible, including young people. Vaccinated youth can safely go to school or camp, play sports, and be with their friends and families, all of which are important for their current and future health and well-being - and all of which were curtailed during the pandemic. The FDA reviewed a study of more than 2,259 U.S. children ages 12 through 15. Of this group, about half were given the Pfizer-BioNTech COVID-19 vaccine, and the other children were given an inactive (placebo) shot. The results suggest that the vaccine is 100% effective at preventing COVID-19. In this age group, kids now make up an increasingly large share of the cases. There were at least American Academy of pediatrics 243,000 cases of COVID-19 in children from Sept 2 to Sept 9 Sept 9 in the U.S. (roughly 29% of all cases in the country).

11.
Journal of Pediatric Gastroenterology and Nutrition ; 75(Supplement 1):S28-S29, 2022.
Article in English | EMBASE | ID: covidwho-2057807

ABSTRACT

Background Current therapies for pediatric and adult eosinophilic esophagitis (EoE) include dietary elimination, proton pump inhibitors, swallowed corticosteroids, and biologics. Our aim is to systematically assess the efficacy and safety of published randomized controlled trials (RCTs) of medical therapies for EoE that compare active treatments to placebo or to an active comparator. We consider RCTs that target the induction and maintenance phases of therapy, separately. Methods A search was designed by a Cochrane information specialist and included Cochrane Gut Register, CENTRAL, MEDLINE, Embase, and clinicaltrials.gov databases, from inception to May 2022. Studies that met our search criteria were imported into Covidence for title and review. All authors participated in study screening, and each study was independently evaluated by two authors. Reports of RCTs that met the inclusion criteria were selected for full text review. Multiple reports of the same RCT were collapsed into the parent study. Data from these studies was then extracted to RevMan Web to assess study characteristics, including study design, EoE definition, inclusion / exclusion criteria, age range, interventions, number of patients randomized, number of patients who completed the study, primary and secondary outcomes and conflicts of interest. Studies were also assessed for potential sources of bias including baseline imbalance, selection, performance, detection, attrition, and reporting biases. We used Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) to assess the overall certainty of evidence supporting the primary outcome. Results As of May 2022, we identified 2,638 reports that met our search criteria of which 14 were duplicates, giving a total of 2,624 reports that were imported into Covidence for further review. Following title and screening, 259 reports were selected for full text review, which were collapsed into 46 distinct RCTs that met the inclusion criteria. The primary outcomes for our systematic review were histological improvement, endoscopic improvement, and clinical symptom improvement, all as defined by the study at study endpoint, and withdrawals due to adverse events. The secondary outcomes of our analysis were serious adverse events, endocrine complications, growth concerns, infections, and health-related quality of life. Study outcomes were analyzed on an intention-to-treat basis. Risk ratios (RRs) and corresponding 95% confidence intervals (95% CI) are reported for dichotomous outcomes, and mean difference and standard deviation are reported for continuous outcomes. The data will be presented in full. Conclusions Results of this analysis inform clinicians about the efficacy and potential side effects of different medical therapies for EoE in both pediatric and adult populations. Deficiencies in our current knowledge will be highlighted and will provide direction for design of future RCTs in the field. Future research should continue to explore factors that influence initial and subsequent medical therapy selection for people with EoE.

12.
Medical Letter on Drugs and Therapeutics ; 64(1654):105-112b, 2022.
Article in English | EMBASE | ID: covidwho-2057513

ABSTRACT

The FDA has approved tirzepatide (Mounjaro - Lilly), a peptide hormone with activity at both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, to improve glycemic control in adults with type 2 diabetes. Tirzepatide, which is injected subcutaneously once weekly, is the fi rst dual GIP/GLP-1 receptor agonist to become available in the US. Selective GIP receptor agonists are not available in the US;GLP-1 receptor agonists have been available for years. Copyright © 2022, Medical Letter Inc.. All rights reserved.

14.
Journal of the American Academy of Dermatology ; 87(3):AB208, 2022.
Article in English | EMBASE | ID: covidwho-2031398

ABSTRACT

Recommendations for a treat-to-target approach were recently developed to guide systemic therapy for disease control in adults with AD. Recommendations outlined criteria for a 3-month initial acceptable target goal: reduction from baseline ≥1 on a 5-level Patient Global Impression of Severity (PGIS) scale and ≥1 specific disease domain target (≥50% improvement from baseline in Eczema Area and Severity Index [EASI-50];≥50% reduction in Scoring of AD [SCORAD-50];and a reduction from baseline in Worst Pruritus Numerical Rating Scale [WP-NRS] ≥3, Dermatology Life Quality Index [DLQI] ≥4, or Patient Oriented Eczema Measure [POEM] ≥4);and a 6-month optimal target goal: PGIS ≤2 and ≥1 specific disease domain target (EASI-75 or EASI ≤7, SCORAD-75 or SCORAD ≤24, WP-NRS ≤4, DLQI ≤5, POEM ≤7). Achievement of these criteria with once-daily upadacitinib (15 mg and 30 mg) monotherapy was compared with placebo using integrated adult data from MU1 and MU2 trials and nonresponder imputation incorporating multiple imputation for missing values due to COVID-19. Greater proportions of patients treated with upadacitinib 15 mg;30 mg vs placebo (P <.001 for all) achieved the initial acceptable target goal at week 2 (78.9%;82.6% vs 25.0%) and week 16 (72.5%;80.2% vs 22.9%), and the optimal target goal at week 2 (52.8%;64.3% vs 6.3%) and week 16 (56.2%;70.1% vs 13.9%). These results suggest that once-daily oral upadacitinib (15 mg and 30 mg) may help improve standards of care in patients with moderate-to-severe AD by achieving 6-month target goals at 16 weeks and as early as 2 weeks for most patients.

15.
Journal of the American Academy of Dermatology ; 87(3):AB161, 2022.
Article in English | EMBASE | ID: covidwho-2031390

ABSTRACT

Purpose: Evaluate efficacy and safety of onabotulinumtoxin A compared with placebo for treating masseter muscle prominence (MMP). Methods: Adults with bilateral grade 4 (Marked) or 5 (Very marked) MMP on the 5-grade clinician-assessed MMP Scale (MMPS) received onabotulinumtoxinA 72 U, 48 U, or placebo. Primary efficacy endpoint was participants achieving MMPS grade ≤3 at day 90. Participants with grade ≤3 for the MMPS and Participant MMPS (MMPS-P), and participants achieving grade ≥2 in the Participant Self-Assessment of Change (PSAC), were evaluated until day 180. Results: Of 150 participants randomized, 34 (22.7%) discontinued (12 [8.0%] due to COVID-19). The modified intent-to-treat population included 145 participants (mean age, 39.3 years;mean BMI, 24.1 kg/m2;89.7% female;75.9% White). MMPS and MMPS-P responder rates were higher for onabotulinumtoxinA 72 U and 48 U than placebo at days 90 (MMPS: 91.3% and 90.6% vs 21.7%;MMPS-P: 93.5% and 96.2% vs 47.8%;both P <.0001) and 180 (MMPS: 71.7% and 56.6% vs 26.1%;MMPS-P: 87.0% and 86.8% vs 60.9%;both P <.01). More onabotulinumtoxinA 72 U and 48 U participants achieved PSAC grade ≥2 than placebo at days 90 (73.9% and 90.6% vs 21.7%;P <.0001) and 180 (76.1% and 66.0% vs 28.3%;P <.001). Treatment-related adverse events occurred in onabotulinumtoxinA 72 U and 48 U groups (12.2% and 9.4%) vs none in placebo;the majority were mild in severity. Conclusion: A single treatment of onabotulinumtoxinA (72 U and 48 U) reduced MMP and improved lower face contour for up to 6 months. Both dose groups demonstrated favorable safety profiles.

16.
Annals of Clinical Psychiatry ; 34(3):19-20, 2022.
Article in English | EMBASE | ID: covidwho-2030704

ABSTRACT

BACKGROUND: Adjustment disorders are now primary diagnoses in the trauma and stressrelated disorders section of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Adjustment disorder with anxiety (AjDA) is the development of emotional or behavioral symptoms considered excessive in response to stressful events, significantly impairing a person's ability to function in social, occupational, and/ or other situations. Traumatic experiences related to the COVID-19 pandemic may have increased rates of adjustment disorders, especially among those whose life routines were disrupted by pandemic-associated stress and anxiety. PH94B (3b-hydroxy-androsta-4,16-dien-ol) has shown rapid-onset efficacy in the treatment of social anxiety disorder (Liebowitz et al. Am J Psychiatry. 2014). PH94B is a neuroactive steroid administered as a nasal spray that engages olfactory chemosensory neurons, activating subsets of olfactory bulb neurons that project directly to the limbic amygdala regulating fear and anxiety circuits. OBJECTIVE: To assess the efficacy, safety, and tolerability of PH94B in adults with AjDA. METHODS: This is an exploratory, phase 2A, randomized, double-blind, 4-week, placebo-controlled, 2-arm study in adults with AjDA. The primary outcome is change from baseline to week 4 in the Hamilton Anxiety Rating Scale (HAM-A) total score after intranasal administration of PH49B 4 times daily vs placebo. Patients with a DSM-5 diagnosis of AjDA confirmed by the Mini-International Neuropsychiatric Interview (MINI) with Adjustment Disorders Module and a clinician-rated HAM-A score of ≥20 at screening (Visit 1), with ≤15% decrease at baseline (Visit 2, randomization) are eligible for inclusion. Secondary outcomes include change from baseline to week 4 in the Adjustment Disorder New Module Scale (ADNM), the International Adjustment Disorder Questionnaire (IADQ), the Clinical Global Impression of Improvement (CGI-I), and the Patient Global Impression of Change (PGI-C). Change from baseline in the Hamilton Depression Rating Scale (HAM-D) was exploratory. RESULTS: A total of 40 patients will be randomized (1:1 drug to placebo). The study design features the use of the ADNM and IADQ, newly developed according to ICD-11 criteria for evaluation of AjDA. While both are validated, neither has been tested in placebo-controlled clinical trials. Both scales begin with a list of stressors (18 for ADNM and 9 for IADQ);a yes answer to any 1 stressor triggers a series of questions about the frequency and duration of a patient's reaction to the stressor (ADNM) or quantifies symptoms in response to the stressor (IADQ). CONCLUSIONS: Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. Anxiety and impaired functioning are increasing, particularly in response to the COVID-19 pandemic, and no pharmacologic treatment is currently approved by the FDA for AjDA. PH94B, an investigational pherine nasal spray, is also being studied for treatment of other anxiety-related disorders.

17.
Front Commun (Lausanne) ; 72022.
Article in English | MEDLINE | ID: covidwho-2022661

ABSTRACT

Background: The Society of Interdisciplinary Placebo Studies (SIPS) was one of many organizations that hosted a virtual scientific conference in response to the COVID-19 pandemic restrictions. Retaining essential benefits of an in-person conference experience was a primary objective for the SIPS conference planning committee and guided the selection of a virtual platform on which to host the 2021 meeting. This article reports on the methods used to design and analyze an engaging, virtual scientific conference, along with the findings and implications for future meetings. Methods: Participant use of and interaction with different features of the conference platform were recorded and exported for analysis. Additionally, all SIPS conference attendees were invited to complete a brief, online post-conference survey that inquired about their perceptions of the SIPS conference specifically as well as their opinions of virtual and hybrid conferences in general. Using these data, we assessed (1) attendance patterns, (2) level of engagement, and (3) attendee satisfaction. Results: The platform recorded 438 unique, active conference attendees who used either a mobile app, web browser, or both to participate during the 3-day program. Seventy-four percent (N = 324) of active users attended all 3 days with 30 and 26 new attendees on Days 2 and 3, respectively. The connections feature offered on the platform was the most utilized function within the online forum. Attendance in the parallel workshop sessions remained constant across the 3 days, with an average of 44.6% (SD = 6.77) of people moving between workshops within a single session. The two poster sessions had an average of 47.6 (SD = 17.97) and 27.8 (SD = 10.24) unique views per poster, respectively. Eleven percent (N = 48) of attendees completed the post-conference survey. Thirty-six percent of these responders stated they were only able to attend because the conference was offered virtually. Further, the quality of the conference had an average satisfaction rating of 68.08 out of 100 (SD = 22.94). Conclusion: Results of data analyses suggest the virtual platform allowed for those who were unable to attend to join virtually, produced moderate engagement throughout the conference, and that the majority of attendees were satisfied with the quality of the fully-virtual conference. Therefore, incorporating virtual aspects in future in-person conferences could enhance conference experience and participation.

18.
International Journal of Infectious Diseases ; 122:553-558, 2022.
Article in English | Web of Science | ID: covidwho-2015428

ABSTRACT

Objectives: This study aims to assess the efficacy of a combination treatment of doxycycline and zinc in the primary prevention of COVID-19 infection in Tunisian health care workers compared with two control groups.Methods: We conducted a prospective, randomized, double-blind clinical trial over 5 months to deter-mine the efficacy of a preventive combination treatment dose of doxycycline (100 mg/day) and zinc (15 mg/day), compared with a single-dose treatment with doxycycline versus placebo. The effectiveness of preventive treatment was measured by the significant decline in the number of cases of COVID-19 infec-tion and/or a decrease in the viral load as determined by SARS-CoV-2 cycle threshold value using reverse transcription polymerase chain reaction tests.Results: We detected a significant decrease of SARS-CoV-2 infection in the group that received both doxycycline and zinc compared with other participants. We also demonstrated that COVID-19 infection was neither associated with diabetes ( P = 0.51) nor associated with hypertension ( P = 0.99), asthma ( P = 0.52), and chronic obstructive pulmonary disease ( P = 0.27).Conclusion: Our findings indicated that preventive therapy reduced the risk of SARS-CoV-2. These results suggest that the combination of doxycycline and zinc has a protective effect in patients with SARS-CoV-2 infection.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

19.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009660

ABSTRACT

Background: CSCC is the second most common skin cancer with an estimated incidence of 1 million cases per year in the US. While the surgical cure rate for CSCC is > 95%, some pts have high risk of recurrence as assessed by immune status, primary disease stage, extent of nodal involvement, presence of extracapsular extension (ECE), and prior treatment. Postoperative RT is recommended for these pts but relapse with locoregional recurrence or distant metastases may still occur. C-POST is evaluating the efficacy of cemiplimab as adjuvant therapy for pts with high-risk CSCC. Here, we provide summary of the most recent study protocol amendment. Methods: C-POST is a randomized, placebo-controlled, double-blind, multicenter Phase 3 study to evaluate cemiplimab as adjuvant treatment for pts with high-risk CSCC, based on surgical and clinicopathologic findings, who completed surgery and postoperative RT (minimum total dose 50Gy, within 10 weeks before randomization) (NCT03969004). Pts with at least one of the following high-risk features are eligible: (1) nodal disease with (a) ECE and at least one node ≥20 mm or (b) at least three lymph nodes positive on surgical pathology report, regardless of ECE;(2) in-transit metastases;(3) T4 lesion;(4) perineural invasion;and (5) recurrent CSCC with at least one other risk factor. Pts with CSCC involvement in at least three lymph nodes (feature 1b) were added to the eligibility criteria, as this group was found to be at similar risk of CSCC recurrence as the initially planned study population. Protocol amendment now allows patients with chronic lymphocytic leukemia (CLL) who are not on active treatment to be enrolled. The study has two parts. In Part 1 (blinded), pts are randomly assigned 1:1 to receive cemiplimab 350 mg or placebo intravenously every 3 weeks for 12 weeks, followed by cemiplimab 700 mg or placebo every 6 weeks for 36 weeks. In optional Part 2 (unblinded), pts in the placebo arm who experience disease recurrence and pts in the cemiplimab arm who experience disease recurrence ≥3 months after completion of 48-week treatment in Part 1 are eligible to receive open-label cemiplimab for up to 96 weeks. The trial is expected to enrol 412 pts from about 100 sites in North and South America, Europe, and Asia-Pacific regions. Key primary objective is to compare disease-free survival;secondary objectives include evaluating overall survival, freedom from locoregional relapse, and distant relapse with adjuvant cemiplimab versus placebo in patients with high-risk CSCC. This study is once again open for enrolment following interruptions owing to the COVID-19 pandemic.

20.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009659

ABSTRACT

Background: Gal-3 is a protein that binds specifically to N-acetylglucosamine-expressing carbohydrates, which are upregulated on key tumorigenic cell surface proteins. Gal-3 is widely over-expressed in the tumor microenvironment and is generally linked to poor outcomes. Gal-3 regulates immune cell function of T cells and macrophages, and promotes neovascularization and fibrosis [Peng Cancer Res 2008;Markowska J Biol Chem 2011;Kouo Cancer Immunol Res 2015]. Gal-3 sequesters interferon gamma, reduces T-cell influx, and contributes to tumor cell evasion of the immune system via LAG-3 activation [Chen PNAS 2009;Gordon-Alonso Nat Commun 2017]. Gal-3 has been identified as a marker of resistance to checkpoint inhibitors (CPIs);patients with stage IV NSCLC with high Gal-3 levels (> 70% Gal-3 immunohistochemical staining) have been shown to be resistant to the CPI pembrolizumab [Capalbo Int J Mol Sci 2019]. Animal data indicate synergy between CPI therapy and Gal-3 inhibition [Vuong Cancer Res 2019;Zhang FEBS Open Bio 2021]. Thus, inhibiting Gal-3 together with CPI-based immunotherapy may enhance tumor-specific immune responses, and overcome CPI resistance. Methods: GALLANT-1 (NCT05240131) is a 3-part, placebo-controlled phase Ib/IIa trial that will investigate safety and efficacy of GB1211 (a Gal-3 inhibitor) + atezo vs placebo + atezo in patients with advanced NSCLC. Part A will include 8-12 patients and study safety and tolerability of 200 mg and 400 mg GB1211 twice-daily + atezo (open-label). Primary endpoint is number of adverse events (AEs) after 12 weeks' treatment and will determine the dosage for Part B. Part B will include 75-94 patients, and is a randomized, double-blind study of GB1211 + atezo or placebo + atezo. Primary endpoints are safety (number of AEs) and efficacy (percentage change from baseline in the sum of longest diameter of target lesions after 12 weeks' treatment). Part C is an expansion study including patients from Parts A and B, with safety and efficacy assessments. Eligibility criteria: advanced or metastatic stage IIIB or IV NSCLC adenocarcinoma;measurable disease per RECIST v1.1;expression of programmed death ligand-1 on ≥50% of tumor cells;eligible for 1200 mg atezo every 3 weeks. Exclusion criteria: symptomatic, untreated, or actively progressing central nervous system metastases;prior systemic chemotherapy for treatment of recurrent advanced or metastatic disease, except if part of neoadjuvant/ adjuvant therapy;prior treatment with immune CPIs and/or GB1211;presence of EGFR mutation and ALK, ROS1, and RET alterations;treatment with antineoplastic or systemic immunotherapeutic agents prior to first GB1211 dose;severe infectious disease < 4 weeks prior to first GB1211 dose;active hepatitis B or C, HIV, or COVID-19. The study is being initiated;updated enrollment status will be presented at the meeting.

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