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Covid-19 virus variants identified so far are due to viral genetic diversity, genetic evolution, and variable infectivity, suggesting that high infection rates and high mortality rates may be contributed by these mutations. And it has been reported that the targeting strategies for innate immunity should be less vulnerable to viral evolution, variant emergence and resistance. Therefore, the most effective solution to Covid-19 infection has been proposed to prevent and treat severe exacerbation of patients with moderate disease by enhancing human immune responses such as NK cell and T cell. In previous studies, we demonstrated for the first time that gamma-PGA induced significant antitumor activity and antiviral activity by modulating NK cell-mediated cytotoxicity. Especially intranasal administration of gamma-PGA was found to effectively induce protective innate and CTL immune responses against viruses and we found out that gamma-PGA can be an effective treatment for cervical intraepithelial neoplasia 1 through phase 2b clinical trial. In this study, the possibility of gamma-PGA as a Covid-19 immune modulating agent was confirmed by animal experiments infected with Covid-19 viruses. After oral administration of gamma-PGA 300mug/mouse once a day for 5 days in a K18-hACE2 TG mouse model infected with SARS-CoV-2 (NCCP 43326;original strain) and SARS-CoV-2 (NCCP 43390;Delta variant), virus titer and clinical symptom improvement were confirmed. In the RjHan:AURA Syrian hamster model infected with SARS-CoV-2 (NCCP 49930;Delta variant), 350 or 550 mug/head of gamma-PGA was administered orally for 10 days once a day. The virus for infection was administered at 5 x 104 TCID50, and the titer of virus and the improvement of pneumonia lesions were measured to confirm the effectiveness in terms of prevention or treatment. In the mouse model infected with original Covid-19 virus stain, the weight loss was significantly reduced and the survival rate was also improved by the administration of gamma-PGA. And gamma-PGA alleviated the pneumonic lesions and reduced the virus titer of lung tissue in mice infected with delta variant. In the deltavariant virus infected hamster model, gamma-PGA showed statistically significant improvement of weight loss and lung inflammation during administration after infection. This is a promising result for possibility of Covid-19 therapeutics along with the efficacy results of mouse model, suggesting gammaPGA can be therapeutic candidate to modulate an innate immune response for Covid-19.
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Aims: To upskilling PN to undertake diabetes clinics and ensure high quality healthcare for our patients by maintain the nursing workforce in primary care. Method(s): The programme was delivered over two days, one month apart with follow up day's at six months and 1 year. During Covid-19 we had adapted the session to 4 half days over a 2 month period and are waiting to do our follow up day face to face. The programme included a broad range of topics and skills required to undertake diabetes clinics. Result(s): 13 PN attended from different geographical areas in our healthboard;having a various amount of experience as a PN from 16 yrs to 1 month but limited diabetes experience. Through anonymous questionnaire responses we showed an improvement in confidence across a broad range of core skills and management. Asked if they felt individually confident pre and post course -new diabetes diagnosis (38% to 92%), hypoglycaemia (53% to 92%), pens and meters (8% to 76%), sick day rules (30% to 84%), foot screening (61% to 92%) and advising on oral medication (30% no confidence improving to 84%). Increasing PN knowledge will ultimately improve patient's care thus reducing the risk of complications. preceptorship throught the course was offered by experience Diabetes Specialist Nurses. Conclusion(s): Even in these challenging times we have to maintain a skilled workforce by delivering education and preceptorship to PN. The Supporting prActice Nurses in Diabetes, Revalidation and Appraisal programme provides PN the tools to undertake diabetes clinics with confidence and ensure excellent patient care.
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The most common causes of acute hepatitis in children are hepatitis A and autoimmune hepatitis. Hepatitis in the course of Wilson's disease is sporadically registered in adolescents. An increase of activity of aminotransferases both in the course of multisystem inflammatory syndrome in children (MIS-C) and in the course of COVID-19 has been observed. Hepatitis is common in children with MIS-C and is associated with a more severe presentation and persistent elevation of liver function tests. To date, no cases of acute hepatitis in children due to COVID-19 have been reported. We present 2 cases of acute hepatitis in children where the only cause seems to be a previous asymptomatic SARS-CoV-2 infection.Copyright © 2023 Termedia Publishing House Ltd.. All rights reserved.
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Background: During the coronavirus disease 2019 (COVID-19) pandemic, established best practices in cancer care were modified to diminish the risk of COVID-19 infection among patients and health-care workers. Objective(s): We aimed to study the modifications in cancer-directed therapy during the first wave of the COVID-19 pandemic. Material(s) and Method(s): A cross-sectional study of patients with cancers of the head and neck, thoracic, urologic, and central nervous systems who visited the medical oncology department of the Tata Memorial Hospital, Mumbai, India, between April 22, 2020 and June 01, 2020, was conducted. Data were prospectively collected in an online pro forma and supplemented from the electronic medical records. Result(s): Of a total of 514 patients, 363 (71%) were men. The most common malignancy was lung cancer in 234 patients (46%). Cancer-directed therapy was modified in 83 patients (16%). Deviations consisted of modification of the chemotherapy regimen (48%), temporary discontinuation of chemotherapy in 37%, and interim chemotherapy to delay surgery in 5%. Changes in the chemotherapy regimen included a shift to a less intensive regimen in 45%, changing from intravenous to oral in 40%, and less frequent dosing of immunotherapy in 7%. Considering missed appointments as a deviation from planned cancer therapy, 68% of patients had a deviation in the standard planned cancer care. Conclusion(s): Almost two-thirds of the patients could not reach the hospital during the COVID-19 pandemic lockdown in India. Of those who could reach the hospital, one of out every six patients with cancer had a change in their cancer-directed treatment, half of which consisted of a modification in the standard chemotherapy regimens. The effects of these therapy deviations are likely to be long-lasting. (Clinical Trials Registry-India, CTRI/2020/07/026533).Copyright © 2023 Neurology India, Neurological Society of India Published by Wolters Kluwer - Medknow.
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BACKGROUND: One-third of pregnant women will experience worsening asthma requiring emergency hospitalization. However, no report comprehensively discussed the management of asthma attacks in pregnant women in impoverished settings. We attempt to illuminate what general practitioners can do to stabilize and improve the outcome of severe acute asthma exacerbations in primary care with resource limitations. CASE REPORT: A nulliparous 29-year-old woman in her 21st week of pregnancy presented severe acute asthma exacerbation in moderate persistent asthma with uncontrolled asthma status along with gestational hypertension, uncompensated metabolic acidosis with a high anion gap, anemia, respiratory infection, and asymptomatic bacteriuria, all of which influenced her exacerbations. This patient was admitted to our resource-limited subdistrict hospital in Indonesia during the COVID-19 pandemic for optimal stabilization. Crystalloid infusions, oxygen supplementation, nebulized beta-agonist with anticholinergic agents, inhaled corticosteroids, intravenous methylprednisolone, broad-spectrum antibiotics, subcutaneous terbutaline, mucolytics, magnesium sulphate, oral antihypertensives, and continuous positive airway pressure were used to treat her life-threatening asthma. After she was stabilized, we referred the patient to a higher-level hospital with more advanced pulmonary management under the supervision of a multidisciplinary team to anticipate the worst scenario of pregnancy termination. CONCLUSION(S): Limitations in primary care, including the lack of sophisticated intensive care units and laboratory panels, may complicate challenges in managing severe acute asthma exacerbation during pregnancy. To enhance maternal-fetal outcomes, all multidisciplinary team members should be well-informed about key asthma management strategies during pregnancy using evidence-based guidelines regarding the drug, rationale, and safety profile.Copyright © 2023 Muhammad Habiburrahman, Triya Damayanti, Mohammad Adya Firmansha Dilmy, Hariyono Winarto.
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Background: Patients with cancer are at a higher risk of getting infected with the severe acute respiratory syndrome coronavirus 2 owing to their immunocompromised state. Providing care to these patients amidst the first wave of the coronavirus disease-2019 (COVID-19) pandemic was extremely challenging. Objective(s): This study was aimed at evaluating the clinical profile and disease-related outcomes of pediatric patients with hematological illnesses and cancer. Material(s) and Method(s): This retrospective study was conducted at a tertiary care center in North India during the first wave of the pandemic from March 2020 to December 2020. Children aged up to 18 years, who were treated for a hematological illness or malignancy or underwent hematopoietic stem cell transplantation (HSCT) and tested positive for COVID-19 regardless of symptoms were included in the study. Baseline demographic data related to the age, diagnosis, treatment status, and chemotherapy protocol used were collected. Outcomes including the cure rates, comorbidities, and sequelae were recorded. Result(s): A total of 650 tests for COVID-19 were performed for 181 children;22 patients were found to be COVID-19 positive. The most common diagnosis was acute leukemia (63.6%). None of the patients developed COVID-19 pneumonia. The majority of patients had asymptomatic infection and were managed at home. Among those with a symptomatic infection, the most common symptoms were fever and cough. A total of 3 (13.6%) patients needed oxygen therapy, one developed multisystem inflammatory syndrome of children leading to cardiogenic shock. Three patients required intensive care or respiratory support;all the patients had favorable clinical outcomes. The median time from the onset of COVID-19 to a negative result on the reverse transcription-polymerase chain reaction test was 21.3 days. Cancer treatment was modified in 15 patients (68.2%). Conclusion(s): Our results suggest that children with hemato-oncological illnesses rarely experience severe COVID-19 disease. The impact of the first wave of COVID-19 primarily manifested as disruptions in the logistic planning and administration of essential treatment to these children rather than COVID-19 sequelae.Copyright © 2021 Cancer Research, Statistics, and Treatment Published by Wolters Kluwer - Medknow.
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Clinical presentation of COVID-19 infection can be variable in the current pandemic even in patients presenting to the clinic with a mild history of upper respiratory complaints. Various cutaneous manifestations have been noticed in COVID-19 patients with herpes zoster (HZ) being one among them. HZ is an infection that results when varicella zoster virus reactivates from its latent state in the posterior dorsal root ganglion. Here, we aim to expand our knowledge by reporting three cases of associated zoster infection in COVID-19 patients admitted to our intensive care unit in view of respiratory complaints. All the three patients admitted, had revealed lymphocytopenia at the time of HZ diagnosis, and were managed conservatively throughout the course. In all the cases, acyclovir/valacyclovir led to the resolution of lesions in 10 days. No postherpetic sequelae were observed. We here suggest that the clinical presentation of HZ at the time of the current pandemic should be considered as an alarming sign for a latent subclinical SARS CoV-2 infection and thorough follow-up of such patients be adopted.Copyright © 2021 Bali Journal of Anesthesiology. All rights reserved.
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Autoimmune pulmonary alveolar proteinosis (PAP) is a rare disease, especially in pediatrics, but important to consider, as it may avoid unnecessary and/or invasive investigations and delayed diagnosis. This case report highlights an adolescent girl with rapid onset dyspnea but an unremarkable physical exam and initial testing. However, due to a high index of suspicion, a chest computed tomography (CT) scan was done, revealing a "crazy paving" pattern, which then prompted expedited assessment. This finding, however, is not as specific as often discussed and has a broad differential diagnosis, which will be reviewed in detail as part of this case. Furthermore, this report demonstrates a diagnostic approach for PAP that avoids lung biopsy, previously considered to be required for diagnosis of PAP, but is increasingly becoming unnecessary with more advanced blood tests and understanding of their sensitivity and specificity. Additionally, management strategies for PAP will be briefly discussed.Copyright © 2022 Canadian Thoracic Society.
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Background: ALG-000184 is a prodrug of ALG-001075, a novel, potent, pan-genotypic Class II CAM. CAMs are thought to have two mechanisms of action (MoA). The primary MoA affects pgRNA encapsidation resulting in inhibition of HBV DNA/RNA replication, as confirmed in CHB subjects receiving ALG-000184. The secondary MoA, which occurs at higher concentrations, regulates the establishment and replenishment of cccDNA, resulting in lowering of HBsAg, an effect that has not been reported to date with ALG- 000184. Method(s): ALG-000184-201 is a multi-part, multicenter, doubleblind, randomized, placebo-controlled study. In healthy volunteers (HVs), single doses up to 500 mg and multiple doses up to 250 mg were well tolerated with linear PK (Gane E., HBV TAG and APASL 2021). In treatment naive (TN) subjects with CHB, daily oral doses of 10-100 mg ALG-000184 for 28 days were well tolerated with linear PK and were associated with profound reductions of DNA/RNA regardless of HBeAg status or dose (Yuen MF, EASL 2022). Plasma exposures required to engage the secondary MoA are expected to be achieved at the 300 mg dose level. Data from a 300 mg cohort treated for 28 days are described here. Data from another ongoing cohort treated with 300 mg for 12 weeks will be presented at the conference. Result(s): Ten subjects were randomized to 300 mg ALG-000184 for 28 days and two to placebo. Two subjects randomized to ALG- 000184 were replaced due to missing data due to Covid-19 lockdown. Subjects were Asian, HBeAg positive, and genotype B or C. Mean baseline HBV DNA and RNA levels were 8.4 log10 IU/mL and 7.3 log10 copies/mL, respectively. One subject experienced a serious adverse event (AE) of pneumothorax>8 weeks after last dose which was considered unlikely related to study drug. No subjects prematurely discontinued study drug. All treatment emergent AEs were Grade <= 2 except for 4 Grade >= 3 alanine aminotransferase (ALT) elevations, which an independent ALT Flare Committee assessed as not related to study drug toxicity. PK was similar to HBeAg negative and HV cohorts following body weight adjustment. Subjects dosed with 300 mg ALG-000184 experienced mean declines of 4.0 log10 IU/mL and 2.6 log10 copies/mL in HBV DNA and RNA levels, respectively, at Day 28. Three of 7 evaluable subjects who received ALG-000184 had HBsAg declines>0.2 log10 IU/mL (0.23-0.78 log10 IU/mL). One subject receiving ALG-000184 had unquantifiable HBsAg throughout the study. Additionally, one HBeAg positive subject in a prior 100 mg cohort had plasma exposures equivalent to the 300 mg dose level and experienced a 0.5 log10 IU/mL HBsAg decline. Conclusion(s): In TN HBeAg positive CHB subjects, 300 mg ALG- 000184 for 28 days was well tolerated, exhibited predictable PK and resulted in rapid and substantial declines in HBV DNA and RNA. Notably, 3 of 7 evaluable subjects from this cohort experienced HBsAg declines of up to 0.78 log10 IU/mL. These data suggest that ALG-000184 can engage the secondary MoA of CAM II. Cohorts evaluating 300 mg over longer durations are planned or ongoing.
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The efficacy of mefloquine has not been studied in the in vivo experiments and clinical trials involving COVID-19 patients. The study was aimed to assess the effects of mefloquine on the SARS-CoV-2 accumulation in the lungs of infected animals and to study the efficacy and safety of mefloquine compared to hydroxychloroquine in patients with COVID-19. During the experiment, a total of 96 Syrian hamsters were infected with SARS-CoV-2. Accumulation of the virus in lungs was compared in the groups of animals treated with mefloquine and ribavirin and in the control group. During the clinical trial, the mefloquine and hydroxychloroquine safety and efficacy in patients with mild and moderate COVID-19 (172 individuals) was assessed based on the symptom changes over time and the computed tomography results. The experiment showed that the SARS-CoV-2 accumulation in the lungs of Syrian hamsters 6 days after infection and mefloquine treatment was 2.2 +/- 0.18 lg PFU/g, which was lower (p < 0.05) than in the control group (3.5 +/- 0.21 lg PFU/g) and ribavirin group (5.2 +/- 0.05 lg PFU/g). During the clinical trial, it was found that 50.0% of patients in the mefloquine group and 32.4% in the hydroxychloroquine group (p < 0.05) developed a mild disease, and the completely resolved respiratory failure was registered in 76.5% and 44.6%, respectively (p < 0.001). Adverse events were observed in 86.7 % and 77% of patients in the mefloquine and hydroxychloroquine groups, respectively (p > 0.05). Thus, during the experiment, mefloquine contributed to the faster virus titer reduction in the lungs. During the clinical trial, the mefloquine efficacy was non-inferiority or, based on a number of indicators, higher compared to hydroxychloroquine, with comparable safety.Copyright © Extreme Medicine.All right reserved.
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Introduction: Coronavirus disease 2019 (COVID-19) has caused thousands of deaths since it was declared as a pandemic. Recently it continues to be one of the most followed topics in the world in terms of its course and treatment. Favipiravir is a broad-spectrum anti-viral agent that has been shown to be effective against various Coronaviruses in vitro. However, as with any drug use, side effects may develop with the use of favipravir treatment. Case Report: We reported a 55-year-old female patient with acute urticarial with angioedema whom had COVID-19 pneumonia. She had no history of allergy, atopy, previous similar episodes or family history of hereditary angioedema. There is no drug or food consumption that may be suspicious in terms of allergy described by the patient other than favipravir. Conclusion(s): As far as we know, it is the first case reported from our country. Since there is no specific examination for differential diagnosis, we cannot distinguish as a rare side effect due to favipiravir treatment or COVID-19 cutaneous manifestation. As a result, studies involving more cases of COVID-19 skin findings are needed.© Copyright 2020 by Emergency Physicians Association of Turkey.
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A patient presented with COVID-19-induced enteritis and colitis associated with a high D-dimer. Serotonin released by activated platelets can lead to inflammation and multiorgan failure in COVID-19 infection. Cyproheptadine blocks serotonin receptors. In light of a prior report that showed that cyproheptadine successfully treated neurologic sequelae in COVID-19, we applied this treatment to this patient. Rapid clinical improvement and reduction of D-dimer occurred after 3 doses of cyproheptadine. This inexpensive, well-Tolerated, oral medication may be applicable to treat hyperinflammatory sequelae of COVID-19 infection.Copyright © 2023 American College of Gastroent. All rights reserved.
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Background: Implementation of vaccination programmes has had a transformational impact on control of the SARS-CoV-2 pandemic, but the need for effective antiviral drugs remains. Molnupiravir (MPV) targets viral RNA polymerase inhibiting replication via lethal mutagenesis and nirmatrelvir (NTV) is a protease inhibitor boosted with ritonavir when given clinically. This study aimed to assess the virological efficacy of NTV and MPV individually and in combination against the SARS-CoV-2 BA.1 Omicron variant in a K18-hACE2 mouse model. Method(s): K18-hACE2 mice were inoculated intranasally with 103 PFU of SARSCoV-2 BA.1 Omicron (B.1.1.529). After 24 hours, mice were orally dosed q12H, as outlined in Figure 1. At 2, 3, and 4-days post infection mice were sacrificed, and lung samples harvested. Animals were weighed and monitored daily throughout. Subsequently, viral replication in the lung was quantified using qRT-PCR to measure total (N-gene) and sub-genomic (E-gene) viral RNA. Data were normalized to 18S for quantitation. Viral exposures expressed as Areas Under viral load Curves (AUCs) were calculated by the trapezoidal method using mean values at each timepoint. Separate studies in Syrian golden hamsters using individual drugs were also conducted, and total serum IgG was measured by ELISA at 4-days post infection. Result(s): Mice gained weight in all groups post-treatment, with no significant difference between groups. A reduction in lung viral exposure was evident in all treatment groups compared to the vehicle control dosed mice (Figure 1). Coadministration of NTV with MPV displayed a trend towards lower lung viral exposure compared to the vehicle control with ~40-and ~45-fold reduction in AUC for N-and SgE-gene assays, respectively. Dosed individually, NTV and MPV reduced viral exposure 5.7-and 7.7-fold for the N-gene assay, respectively. Differences in total serum IgG concentrations were evident between vehicle and NTV-(34-fold reduction, P=0.018), and MPV-(4.2-fold reduction, P=0.053) treated hamsters. Conclusion(s): These data show virological efficacy of NTV and MPV against the SARS-CoV-2 BA.1 Omicron variant. The combination of NTV and MPV demonstrated a lower viral RNA exposure in the lung than either drug alone, albeit not statistically significant. Initial data indicate potential immune alterations in NTV and MPV dosed hamsters. Studies to clarify the utility of NTV/ MPV combinations and further characterize the impact of antiviral therapy on IgG are warranted.
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The management of patients with cognitive impairment (CI) is one of the urgent problems of modern medicine. Issues of diagnostics and therapy of patients with CI and their high mortality during the period of coronavirus infection are discussed. A wide prevalence of patients with mild CI (MCI), an important role of neuropsychological research in establishing CI, and frequent diagnosis of CI only at the stage of dementia were noted. In our country, CI is poorly diagnosed, the most common cause of CI in the elderly - Alzheimer's disease (AD) - is rarely established, patients are observed for a long time with a diagnosis of cerebrovascular disease (CVD). Some non-drug and drug methods can reduce the manifestations of CI, improve the quality of life of both the patients themselves and those around them. In severe CI, socio-psychological methods, stimulating patients to feasible household and social, physical and mental activity, and avoiding prolonged hospitalization are of primary importance. In addition to lifestyle changes, much attention in CI is given to the prevention of stroke, the treatment of arterial hypertension and diabetes mellitus. At the stage of dementia, cholinomimetic drugs (acetylcholinesterase inhibitors, donepezil, rivastigmine, galantamine) and the glutamate receptor blocker memantine are used. The use of choline alfoscerate in CI and the results of the multicenter, placebo-controlled ASCOMALVA study are discussed, in which, in patients with AD and CVD, the addition of choline alfoscerate to donepezil reduced the severity of CI, manifestations of depression, anxiety, and apathy. A new oral form of choline alfoscerate (Cerpechol) is reported that may improve patient compliance and be used in patients with swallowing disorders.Copyright © 2023 Ima-Press Publishing House. All rights reserved.
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Hepatitis A is a common viral infection worldwide that is transmitted via the fecal-oral route. Since the introduction of an efficient vaccine, the incidence of infection has decreased but the number of cases has risen due to widespread community outbreaks among unimmunized individuals. Classic symptoms include fever, malaise, dark urine, and jaundice, and are more common in older children and adults. People are often most infectious 14 days prior to and 7 days following the onset of jaundice. We will discuss the case of a young male patient, diagnosed with acute hepatitis A, leading to fulminant hepatitis refractory to conventional therapy and the development of subsequent kidney injury. The medical treatment through the course of hospitalization was challenging and included the use of L-ornithine-L-aspartate and prolonged intermittent hemodialysis, leading to a remarkable outcome. Hepatitis A is usually self-limited and vaccine-preventable;supportive care is often sufficient for treatment, and chronic infection or chronic liver disease rarely develops. However, fulminant hepatitis, although rare, can be very challenging to manage as in the case of our patient.Copyright © 2023 The Author(s).
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The pharmacokinetic (PK) drug-drug interactions (DDIs) of nelfinavir and cepharanthine combination is limited information in human. In addition, the dosage regimen of this combination is not available for COVID-19 treatment. The objective of this study was to perform in silico simulations using GastroPlusTM software to predict physicochemical properties, PK parameters using the physiologically based pharmacokinetic (PBPK) model of healthy adults in different dosage regimens. The DDIs analysis of nelfinavir and cepharanthine combination was carried out to optimize the dosage regimens as a potential against COVID-19. The Spatial Data File (SDF) format of nelfinavir and cepharanthine structures obtained from PubChem database were used to carry out in silico predictions for physicochemical properties and PK parameters using several aspects of modules such as ADMET Predictor, Metabolism and Transporter, PBPK model. Subsequently, all data were utilized in the DDIs simulations. The dynamic simulation feature was selected to calculate and investigate the Cmax, AUC0-120, AUC0-inf, Cmax ratio, AUC0-120 ratio, and AUC0-inf ratio. The victim or nelfinavir dosage regimens were used four oral administration regimens of 500 mg and 750 mg in every 8 and 12 hours for simulations. The perpetrator or cepharanthine oral dosage regimens were used in several regimens from 10 mg to 120 mg in every 8, 12, and 24 hours. From all predicted results, the dosage regimen as a potential combination against COVID-19 was nelfinavir 500 mg every 8 hours and cepharanthine 10 mg every 12 hours.Copyright © 2023 by Faculty of Pharmacy, Mahidol University, Thailand is licensed under CC BY-NC-ND 4.0. To view a copy of this license, visit https://www.creativecommons.org/licenses/by-nc-nd/4.0/.