Publications by authors named "Andrew Ustianowski"
Health outcomes 3 months and 6 months after molnupiravir treatment for COVID-19 for people at higher risk in the community (PANORAMIC): a randomised controlled trial.
Lancet Infect Dis
January 2025
Article Synopsis
- The study follows the PANORAMIC trial, investigating the long-term effectiveness of molnupiravir for COVID-19 on wellbeing, persistent symptoms, new infections, healthcare use, and time off work at 3 and 6 months post-randomization.
- Participants included adults over 50 or younger with specific health issues, who were affected by COVID-19 for less than 5 days and were divided into either a molnupiravir treatment group or a standard care group.
- The trial involved 25,783 participants and aimed to assess various secondary outcomes, including self-reported wellness, symptom severity, health-related quality of life, and overall healthcare usage after the initial
Article Synopsis
- Clinicians evaluate patient factors such as polypharmacy and comorbidities when prescribing treatments for COVID-19, particularly focusing on direct-acting antivirals (DAAs).
- The study analyzed data from over 788,000 hospitalized COVID-19 patients to identify potential drug-drug interactions (DDIs) that could affect the use of DAAs like nirmatrelvir/ritonavir, remdesivir, and molnupiravir.
- Findings revealed that a significant portion of patients (52%) received medications either contraindicated or to be avoided with nirmatrelvir/ritonavir, especially in older patients and those with higher comorbidity scores.
Objectives: Our objective was to describe the prevalence of cardiovascular disease (CVD) risk factors in people of African ancestry with HIV in the UK.
Methods: We conducted a cross-sectional analysis of CVD risk factors in Black people with HIV aged ≥40 years and estimated the 10-year CVD risk using QRISK®3-2018. Correlations between body mass index (BMI) and CVD risk factors were described using Pearson correlation coefficients, and factors associated with 10-year CVD risk ≥5% were described using logistic regression.
The UK has fallen from fourth to 10th place in the global ranking for clinical trial activities in the past 6 years. Due to the limited capacity of the clinical trial pharmacy workforce and delays in providing pharmacy approvals, pharmacy has been identified as one of the constraining services that delays the set-up and delivery of clinical trials. To tackle this problem, we developed a single pharmacy review process for multicentre trials across Greater Manchester (GM) and tested its feasibility and implementation in our region.
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- The phase 3 PROVENT and STORM CHASER studies evaluated the efficacy of AZD7442 (tixagevimab/cilgavimab) for preventing symptomatic COVID-19 both before and after exposure to the virus.
- In the PROVENT study, AZD7442 showed a significant reduction in symptomatic COVID-19 cases and severe disease over 15 months, with a relative risk reduction ranging from 46.3% to 91.4%.
- The STORM CHASER study also indicated some efficacy, with a maximum relative risk reduction of 43.3%, but did not show significant long-term benefits, and serious adverse events were similar between those receiving AZD7442 and placebo in both
Article Synopsis
- * Using an SEIR model, researchers assessed various vaccination strategies, concluding that the autumn 2022/spring 2023 booster campaign significantly reduced hospitalizations by 18,921 and deaths by 1,463 compared to not having a booster program.
- * Expanding booster eligibility and increasing uptake further improved health outcomes, yielding twice as many averted ICU admissions and reducing long COVID cases, while also minimizing lost productive days by fivefold.
Article Synopsis
- The study aimed to analyze the impact of COVID-19 on black individuals living with HIV in the UK, focusing on incidence and factors influencing the disease.
- Out of 2,495 participants, 573 had COVID-19, with respective cumulative incidence rates of 31.0% for COVID-19 and 3.4% for severe cases requiring hospitalization or leading to death.
- Key findings revealed that ancestry region, CD4 count, and comorbidities like diabetes and kidney disease significantly affected both the likelihood of acquiring COVID-19 and the severity of the disease.
Importance: Staphylococcus aureus surgical site infections (SSIs) and bloodstream infections (BSIs) are important complications of surgical procedures for which prevention remains suboptimal. Contemporary data on the incidence of and etiologic factors for these infections are needed to support the development of improved preventive strategies.
Objectives: To assess the occurrence of postoperative S aureus SSIs and BSIs and quantify its association with patient-related and contextual factors.
Background & Aims: Short duration treatment may aid HCV elimination among key populations. This study evaluated the efficacy of glecaprevir-pibrentasvir for 4 weeks among people with recent HCV infection.
Methods: In this single-arm multicentre international trial, adults with recent HCV (duration of infection <12 months) received glecaprevir-pibrentasvir 300 mg-120 mg daily for 4 weeks.
Introduction: There is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19.
Methods And Analysis: PANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses.
SARS-CoV-2 has resulted in high levels of morbidity and mortality world-wide, and severe complications can occur in older populations. Humoral immunity induced by authorized vaccines wanes within 6 months, and frequent boosts may only offer transient protection. GRT-R910 is an investigational self-amplifying mRNA (samRNA)-based SARS-CoV-2 vaccine delivering full-length Spike and selected conserved non-Spike T cell epitopes.
View Article and Find Full Text PDFBackground: We report spike protein-based lineage and AZD7442 (tixagevimab/cilgavimab) neutralizing activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants identified from breakthrough infections in the PROVENT preexposure prophylaxis trial.
Methods: Variants identified from PROVENT participants with reverse-transcription polymerase chain reaction-positive symptomatic illness were phenotypically assessed to determine neutralization susceptibility of variant-specific pseudotyped virus-like particles.
Results: At completion of 6 months' follow-up, no AZD7442-resistant variants were observed in breakthrough coronavirus disease 2019 (COVID-19) cases.
Background: COVID-19 is associated with a dysregulated immune response but it is unclear how immune dysfunction contributes to the chronic morbidity persisting in many COVID-19 patients during convalescence (long COVID).
Methods: We assessed phenotypical and functional changes of monocytes in COVID-19 patients during hospitalisation and up to 9 months of convalescence following COVID-19, respiratory syncytial virus or influenza A. Patients with progressive fibrosing interstitial lung disease were included as a positive control for severe, ongoing lung injury.
Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial.
Lancet
January 2023
Background: The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population.
Methods: PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial.
Article Synopsis
- A phase 3 trial evaluated the effectiveness of AZD7442 (tixagevimab/cilgavimab) as a post-exposure preventive treatment for COVID-19 in unvaccinated adults who had been exposed to the virus.
- A total of 1,121 participants were enrolled, with 749 receiving AZD7442 and 372 receiving a placebo, showing mild-to-moderate adverse events mostly in the placebo group.
- Although the study did not meet the primary goal of preventing symptomatic COVID-19 overall, it indicated that AZD7442 significantly reduced the risk of symptomatic infection in those who were confirmed to be virus-negative at the start of the trial.
Introduction: Guidelines have improved the management of prosthetic joint infections (PJI). However, it is necessary to reassess the incidence and risk factors for treatment failure (TF) of Staphylococcus aureus PJI (SA-PJI) including functional loss, which has so far been neglected as an outcome.
Methods: A retrospective cohort study of SA-PJI was performed in 19 European hospitals between 2014 and 2016.
Tixagevimab/cilgavimab for prevention and treatment of COVID-19: a review.
Expert Rev Anti Infect Ther
December 2022
Introduction: There is a need to protect vulnerable individuals who do not respond to vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), particularly following the emergence of new variants. Tixagevimab/cilgavimab, the only monoclonal antibody combination authorized for pre-exposure prophylaxis of coronavirus disease 2019 (COVID-19), demonstrated efficacy in unvaccinated individuals in the PROVENT study.
Areas Covered: This review focuses predominantly on real-world evidence examining the effectiveness and safety of tixagevimab/cilgavimab in populations who are immunocompromised and otherwise vulnerable.
Objectives: We aim to identify the preoperative and perioperative risk factors associated with post-surgical Staphylococcus aureus prosthetic joint infections (PJI) and to develop and validate risk-scoring systems, to allow a better identification of high-risk patients for more efficient targeted interventions.
Methods: We performed a multicenter matched case-control study of patients who underwent a primary hip and knee arthroplasty from 2014 to 2016. Two multivariable models by logistic regression were performed, one for the preoperative and one for perioperative variables; predictive scores also were developed and validated in an external cohort.
Introduction: Variants of the gene are associated with chronic kidney disease (CKD) in people of African ancestry, although evidence for their impact in people with HIV are sparse.
Methods: We conducted a cross-sectional study investigating the association between renal risk alleles and kidney disease in people of African ancestry with HIV in the UK. The primary outcome was end-stage kidney disease (ESKD; estimated glomerular filtration rate [eGFR] of <15 ml/min per 1.
Background: In COVACTA, a randomised, placebo-controlled trial in patients hospitalised with coronavirus disease-19 (COVID-19), tocilizumab did not improve 28-day mortality, but shortened hospital and intensive care unit stay. Longer-term effects of tocilizumab in patients with COVID-19 are unknown. Therefore, the efficacy and safety of tocilizumab in COVID-19 beyond day 28 and its impact on Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) clearance and antibody response in COVACTA were investigated.
View Article and Find Full Text PDFBackground: The monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days.
Methods: In an ongoing phase 3 trial, we enrolled adults (≥18 years of age) who had an increased risk of an inadequate response to vaccination against coronavirus disease 2019 (Covid-19), an increased risk of exposure to SARS-CoV-2, or both.