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Infectious Diseases and Therapy Apr 2024Influenza is a common, seasonal infectious disease with broad medical, economic, and social consequences. Real-world evidence on the effect of influenza treatment on...
INTRODUCTION
Influenza is a common, seasonal infectious disease with broad medical, economic, and social consequences. Real-world evidence on the effect of influenza treatment on household transmission and healthcare resource utilization is limited in outpatient settings in the USA. This study examined the real-world effectiveness of baloxavir vs oseltamivir in reducing influenza household transmission and healthcare resource utilization.
METHODS
This prospective electronic survey on patient-reported outcomes was conducted between October 2022 and May 2023 via CVS Pharmacy in the USA. Adult participants (≥ 18 years old) were eligible if they filled a prescription for baloxavir or oseltamivir at a CVS Pharmacy within 2 days of influenza symptom onset. Participant demographics, household transmission, and all-cause healthcare resource utilization were collected. Transmission and utilization outcomes were assessed using χ and Fisher exact tests.
RESULTS
Of 87,871 unique patients contacted, 1346 (1.5%) consented. Of 374 eligible patients, 286 (90 baloxavir- and 196 oseltamivir-treated patients) completed the survey and were included in the analysis. Mean age of participants was 45.4 years, 65.6% were female, and 86.7% were White. Lower household transmission was observed with baloxavir compared with oseltamivir therapy (17.8% vs 26.5%; relative risk = 0.67; 95% CI 0.41-1.11). Healthcare resource utilization, particularly emergency department visits (0.0% vs 4.6%), was also numerically lower in the baloxavir-treated group; no hospitalizations were reported in either cohort.
CONCLUSIONS
The findings from this real-world study suggest that antiviral treatment of influenza with baloxavir may decrease household transmission and reduce healthcare resource utilization compared with oseltamivir.
PubMed: 38483775
DOI: 10.1007/s40121-024-00937-y -
Frontiers in Oncology 2024Mounting evidence has revealed the anti-cancer activity of various anti-viral drugs. Oseltamivir phosphate (OP), namely Tamiflu, is routinely used to combat influenza...
PURPOSE
Mounting evidence has revealed the anti-cancer activity of various anti-viral drugs. Oseltamivir phosphate (OP), namely Tamiflu, is routinely used to combat influenza infections. Although evidence has indicated the anti-cancer effects of OP and , little information is known about the effect of OP use on cancers in humans.
METHODS
A nationwide population-based cohort study involving 13,977,101 cases with 284,733 receiving OP was performed to examine the association between OP use and cancers using the National Health Insurance Research Database in Taiwan between 2009 and 2018.
RESULTS
The cohort study found that OP users showed a significantly lower incidence of lung cancer, colon cancer, liver, and intrahepatic bile duct cancer, oral cancer, pancreas cancer, esophagus cancer, stomach cancer, and prostate cancer. Additionally, OP users exhibited a lower risk of cancer-related mortality (adjusted HR=0.779; 95% confidence interval [CI] 0.743-0.817; p<0.001) and a reduced risk of developing liver cancer (adjusted HR=0.895; 95% CI 0.824-0.972; p=0.008), esophagus cancer (adjusted HR=0.646; 95% CI 0.522-0.799; p<0.001) and oral cancer (adjusted HR=0.587; 95% CI 0.346-0.995; p=0.048). Notably, OP users had a significant reduction in liver cancer occurrence over a 10-year period follow-up and a lower cancer stage at liver cancer diagnosis.
CONCLUSION
These findings first suggest the beneficial effects and therapeutic potential of OP use for certain cancers, especially liver cancer.
PubMed: 38469236
DOI: 10.3389/fonc.2024.1329986 -
Biomedicine & Pharmacotherapy =... Apr 2024Sphingolipid transporter 1 (SPNS1) is a significant differentially expressed gene (DEGs) in esophageal squamous cell carcinoma (ESCC). According to 3 pairs clinic...
Sphingolipid transporter 1 (SPNS1) is a significant differentially expressed gene (DEGs) in esophageal squamous cell carcinoma (ESCC). According to 3 pairs clinic cohorts, transcriptomic (155 pairs of ESCC samples and GSE53624, and proteomic data from PXD021701 including 124 ESCC samples) we found that SPNS1 was significantly higher in ESCC tissues compared to adjacent normal esophagus tissues. ESCC patients with high SPNS1 had a significantly poorer clinical prognosis than those with low SPNS1. Knockdown of SPNS1 significantly inhibited the proliferation, migration, and invasion abilities of ESCC cells, while promoting apoptosis. And overexpression of SPNS1 exhibited opposite functions. Furthermore, ESCC cells became more sensitive to 5-fluorouracil (5-FU) when SPNS1 was knocked down. Transcriptome sequencing revealed that NEU1 was one significant DEG affected by SPNS1 and positively correlated with SPNS1 expression. Oseltamivir phosphate (OP), one NEU1 inhibitor, markedly reversed 5-FU resistance, migration, and proliferation induced by high expression of SPNS1 both in vivo and in vitro. Our findings indicated that SPNS1 might promote the progression of ESCC by upregulating NEU1 expression and influencing chemotherapy sensitivity. These results provide new perceptions into potential therapeutic targets for ESCC treatment. The present study aimed to investigate the role and underlying mechanism of SPNS1 in ESCC.
Topics: Humans; Esophageal Squamous Cell Carcinoma; Oseltamivir; Esophageal Neoplasms; Proteomics; Cell Line, Tumor; Cell Proliferation; Fluorouracil; Cell Movement; Gene Expression Regulation, Neoplastic
PubMed: 38460365
DOI: 10.1016/j.biopha.2024.116367 -
Neurology India Jan 2024Infection is an important trigger of myasthenic crisis (MC), and those infections manifest with pneumonia and muscle involvement may result in more frequent MC. We...
Infection is an important trigger of myasthenic crisis (MC), and those infections manifest with pneumonia and muscle involvement may result in more frequent MC. We report two myasthenia gravis (MG) patients with H1N1 infection, and highlight the reasons for deterioration. Two patients with MG had H1N1 infection. The diagnosis of MG was confirmed by neostigmine, repetitive nerve stimulation, and anti-acetylcholine receptor antibody tests. H1N1 was confirmed by nucleic acid detection study, and myositis by creatinine kinase. The patient with pneumonia and myositis had MC needing mechanical ventilation for 10 days, and the other patient without myositis did not have MC. They were treated with oseltamivir 75 mg twice daily for 5 days, and the patients with MC received ceftriaxone intravenously. Both the patients were on prednisolone and azathioprine, and none received prior H1N1 vaccination. The lady with MC with myositis was discharged on day 27 in wheelchair bound state, and the other one patient without myositis or MC was discharged on 6th day with full recovery. These patients highlight the need for evaluation for myositis along with pneumonia in the MG patients with H1N1 infection. Vaccination in MG patients on immunosuppression may be useful.
Topics: Humans; Influenza A Virus, H1N1 Subtype; Myasthenia Gravis; Myositis; Neostigmine; Pneumonia
PubMed: 38443018
DOI: 10.4103/neuroindia.NI_482_19 -
Cureus Feb 2024The clinical features and severity of coronavirus disease 2019 (COVID-19) vary between patients and countries. Patients with certain conditions are predisposed to poor...
BACKGROUND
The clinical features and severity of coronavirus disease 2019 (COVID-19) vary between patients and countries. Patients with certain conditions are predisposed to poor outcomes compared with those without medical conditions, such as diabetes, dementia, and hypertension (HTN).
METHODS
The aim of this retrospective study was to assess factors associated with higher mortality in patients with COVID-19 infections and to identify the reason for hospital admission in these patients. The study was performed on patients admitted between 1 and 31 March 2020. Data collection was done retrospectively from electronic medical records.
RESULTS
There were 269 patient admissions during this period, of which 147 were included in this audit. The mean age of COVID-19-positive patients was 62.8 years and 65.9 years for COVID-19-negative patients during this period. Forty-seven patients requiring hospital admission were COVID-19 positive and 93 were COVID-19 negative. There were no COVID-19 swabs in the seven patients included in the audit. Approximately 50% of the COVID-19-positive patients presented with fever and shortness of breath (sob), followed by dyspnea and cough (seven patients). The most common comorbidity was HTN, followed by type 2 diabetes mellitus (T2DM) and ischemic heart disease (IHD). The survival rate was 72.3% in COVID-19-positive patients and 80% in COVID-19-negative patients. The average length of stay was 14.4 days for COVID-19-positive survivors compared to 7.8 days for COVID-19-negative survivors. Most patients who tested positive for COVID-19 infection received oseltamivir vaccination and antibiotics. The presence of HTN, diabetes mellitus (DM), age, and organ failure was associated with a high mortality risk.
CONCLUSION
Our study supports the findings of previous studies that diabetes, HTN, coronary artery disease, old age, and organ failure were associated with high mortality in patients admitted to hospitals with COVID-19 infections.
PubMed: 38435221
DOI: 10.7759/cureus.53432 -
Antiviral Research Apr 2024While clinical trials have illuminated both the virological and clinical efficacy of baloxavir for influenza and post-treatment viral resistance, these aspects warrant... (Observational Study)
Observational Study
While clinical trials have illuminated both the virological and clinical efficacy of baloxavir for influenza and post-treatment viral resistance, these aspects warrant further study in real-world settings. In response, we executed a prospective, observational study of the Japanese 2022-2023 influenza season. A cohort of 73 A(H3N2)-diagnosed outpatients-36 treated with baloxavir, 20 with oseltamivir, and 17 with other neuraminidase inhibitors (NAIs)-were analyzed. Viral samples were collected before and after administering an antiviral on days 1, 5, and 10, respectively. Cultured viruses were amplified using RT-PCR and sequenced to detect mutations. Fever and other symptoms were tracked via self-reporting diaries. In the baloxavir cohort, viral detection was 11.1% (4/36) and 0% (0/36) on day 5 and day 10, respectively. Two isolates from day 5 (5.6%, 2/36) manifested I38T/M-substitutions in the polymerase acidic protein (PA). For oseltamivir and other NAIs, viral detection rates were 60.0% (12/20) and 52.9% (9/17) on day 5, and 16.7% (3/18) and 6.3% (1/16) on day 10, respectively. No oseltamivir-resistant neuraminidase mutations were identified after treatment. Median fever durations for the baloxavir, oseltamivir, and other NAI cohorts were 27.0, 38.0, and 36.0 h, respectively, with no significant difference. Two patients harboring PA I38T/M-substitutions did not exhibit prolonged fever or other symptoms. These findings affirm baloxavir's virological and clinical effectiveness against A(H3N2) in the 2022-2023 season and suggest limited clinical influence of post-treatment resistance emergence.
Topics: Humans; Influenza, Human; Oseltamivir; Neuraminidase; Influenza A Virus, H3N2 Subtype; Outpatients; Seasons; Prospective Studies; Antiviral Agents; Pyridones; Enzyme Inhibitors; Guanidines; Fever; Dibenzothiepins; Morpholines; Triazines
PubMed: 38430970
DOI: 10.1016/j.antiviral.2024.105853 -
Cureus Jan 2024Infective myositis is a rare complication of viral infection, occurring most commonly in children. Here, we present the first case report in Saudi Arabia that describes...
Infective myositis is a rare complication of viral infection, occurring most commonly in children. Here, we present the first case report in Saudi Arabia that describes a four-year-old healthy female who presented to the emergency department with a history of fever associated with coryzal symptoms for four days and a one-day history of bilateral lower limb pain and an inability to walk without assistance. Lower limb pain was not associated with joint pain, swelling, or skin rashes. The respiratory virus panel was positive for influenza A, and she was found to have increased levels of creatine kinase (CK). The patient was diagnosed with viral myositis secondary to influenza type A infection and was admitted for dehydration. She was treated successfully with supportive measures and oseltamivir. The patient's condition improved three days after the initial presentation and was discharged and followed up to ensure resolution. Extensive laboratory assessment and hospitalization can often be deemed unnecessary, given that the majority of cases of viral myositis carry a positive prognosis and are self-limiting. Therefore, it is important to consider viral myositis as a potential diagnosis for a child presenting with difficulties walking, particularly if these symptoms arise following a respiratory infection.
PubMed: 38420103
DOI: 10.7759/cureus.53179 -
Journal of Medical Virology Mar 2024Antiviral therapy based on neuraminidase (oseltamivir) or polymerase (baloxavir marboxil) inhibitors plays an important role in the management of influenza infections....
Antiviral therapy based on neuraminidase (oseltamivir) or polymerase (baloxavir marboxil) inhibitors plays an important role in the management of influenza infections. However, the emergence of drug resistance and the uncontrolled inflammatory response are major limitations in the treatment of severe influenza disease. Protectins D1 (PD1) and DX (PDX), part of a family of pro-resolving mediators, have previously demonstrated anti-influenza activity as well as anti-inflammatory properties in various clinical contexts. Herein, we synthetized a series of simplified PDX analogs and assessed their in vitro antiviral activity against influenza A(H1N1) viruses, including oseltamivir- and baloxavir-resistant variants. In ST6GalI-MDCK cells, the PDX analog AN-137B reduced viral replication in a dose-dependent manner with IC values of 23.8 for A/Puerto Rico/8/1934 (H1N1) and between 32.6 and 36.7 µM for susceptible and resistant A(H1N1)pdm09 viruses. In MTS-based cell viability experiments, AN-137B showed a 50% cellular cytotoxicity (CC ) of 638.7 µM with a resulting selectivity index of 26.8. Of greater importance, the combination of AN-137B with oseltamivir or baloxavir resulted in synergistic and additive in vitro effects, respectively. Treatment of lipopolysaccharide (LPS)-stimulated macrophages with AN-137B resulted in a decrease of iNOS activity as shown by the reduction of nitrite production, suggesting an anti-inflammatory effect. In conclusion, our results indicate that the protectin analog AN-137B constitutes an interesting therapeutic modality against influenza A virus, warranting further evaluation in animal models.
Topics: Animals; Humans; Oseltamivir; Influenza A Virus, H1N1 Subtype; Antiviral Agents; Influenza, Human; Influenza A virus; Anti-Inflammatory Agents; Drug Resistance, Viral; Neuraminidase; Triazines; Dibenzothiepins; Docosahexaenoic Acids; Morpholines; Pyridones
PubMed: 38402600
DOI: 10.1002/jmv.29484 -
Pharmaceutics Feb 2024Hepatic carboxylesterase 1 (CES1) metabolizes numerous prodrugs into active ingredients or direct-acting drugs into inactive metabolites. We aimed to develop a...
Hepatic carboxylesterase 1 (CES1) metabolizes numerous prodrugs into active ingredients or direct-acting drugs into inactive metabolites. We aimed to develop a semi-physiologically based pharmacokinetic (semi-PBPK) model to simultaneously predict the pharmacokinetics of CES1 substrates and their active metabolites in liver cirrhosis (LC) patients. Six prodrugs (enalapril, benazepril, cilazapril, temocapril, perindopril and oseltamivir) and three direct-acting drugs (flumazenil, pethidine and remimazolam) were selected. Parameters such as organ blood flows, plasma-binding protein concentrations, functional liver volume, hepatic enzymatic activity, glomerular filtration rate (GFR) and gastrointestinal transit rate were integrated into the simulation. The pharmacokinetic profiles of these drugs and their active metabolites were simulated for 1000 virtual individuals. The developed semi-PBPK model, after validation in healthy individuals, was extrapolated to LC patients. Most of the observations fell within the 5th and 95th percentiles of simulations from 1000 virtual patients. The estimated AUC and C were within 0.5-2-fold of the observed values. The sensitivity analysis showed that the decreased plasma exposure of active metabolites due to the decreased CES1 was partly attenuated by the decreased GFR. Conclusion: The developed PBPK model successfully predicted the pharmacokinetics of CES1 substrates and their metabolites in healthy individuals and LC patients, facilitating tailored dosing of CES1 substrates in LC patients.
PubMed: 38399287
DOI: 10.3390/pharmaceutics16020234