A comparison of frequentist and Bayesian approaches to the Personalised Randomised Controlled Trial (PRACTical)-design and analysis considerations.

Background: Multiple treatment options frequently exist for a single medical condition with no single standard of care (SoC), rendering a classic randomised trial comparing a specific treatment to a control treatment infeasible. A novel design, the personalised randomised controlled trial (PRACTical), allows individualised randomisation lists and borrows information across patient subpopulations to rank treatments against each other without comparison to a SoC. We evaluated standard frequentist analysis with Bayesian analyses, and developed a novel performance measure, utilising the precision in treatment coefficient estimates, for treatment ranking.

Rationalizing antibiotic prescribing for bacterial pneumonia in patients with reported penicillin allergy-a qualitative study.

Background: Penicillin allergy is commonly reported, yet often mislabelled. Such a label is associated with adverse outcomes in bacterial pneumonia. Despite recognition of the overlabelling of penicillin allergy and the awareness of potential adverse effects, there are limited data on the rationale for the management of patients with bacterial pneumonia and concomitant penicillin allergy.

Antibiotic duration for common bacterial infections-a systematic review.

Background: Reducing antibiotic duration is a key stewardship intervention to mitigate antimicrobial resistance (AMR). We examined current evidence informing antibiotic duration for common bacterial infections to identify any gaps in terms of settings, patient populations and infectious conditions. Trial methodologies were assessed to identify areas for improvement.

Establishing clinical research networks for future infectious disease outbreak responses in Southeast Asia: Report of a workshop on challenges and opportunities.

The COVID-19 pandemic highlighted the critical need for well-established clinical research networks capable of rapid response during infectious disease outbreaks. In Southeast Asia, the absence of active research networks at the onset of the COVID-19 contributed to gaps in regional preparedness. This manuscript discusses the challenges and opportunities identified during a regional workshop held in Singapore (February 26 to March 1, 2024), which brought together 130 stakeholders from across the region.

Informed consent and risk communication challenges in antimicrobial clinical trials: a scoping review.

Objectives: Randomised trials for the management of drug-resistant infections are challenging to conduct as target patient populations often lack decision-making capacity, and enrolment windows are typically short. Improving informed consent and risk communication in these trials is especially crucial for protecting patient interests and maximising trial efficiency. This study aimed to understand challenges in risk communication and informed consent in antimicrobial clinical trials.

Cost-effectiveness of a short-course antibiotic treatment strategy for the treatment of ventilator-associated pneumonia: an economic analysis of the REGARD-VAP trial.

Background: The REGARD-VAP trial showed that individualised shortened antibiotic therapy was non-inferior to usual care for mortality and pneumonia recurrence in patients with ventilator-associated pneumonia (VAP). We aimed to assess the cost-effectiveness of an individualised shortened antibiotic therapy approach in this planned economic analysis.

Methods: REGARD-VAP was a phase 4, multicentre, open-label, randomised trial to assess a short-course antibiotic treatment strategy for treatment of VAP.

Combination Versus Monotherapy for Carbapenem-Resistant Acinetobacter Species Serious Infections: A Prospective IPTW Adjusted Cohort Study.

Introduction: International guidelines recommend definitive combination antibiotic therapy for the management of serious infections involving carbapenem-resistant Acinetobacter (CRAB) species. The commonly available combination options include high-dose sulbactam, polymyxins, tetracyclines, and cefiderocol. Scanty prospective data exist to support this approach.

Reversing Unknown Quantum Processes via Virtual Combs for Channels with Limited Information.

The inherent irreversibility of quantum dynamics for open systems poses a significant barrier to the inversion of unknown quantum processes. To tackle this challenge, we propose the framework of virtual combs that exploits the unknown process iteratively with additional classical postprocessing to simulate the process inverse. Notably, we demonstrate that an n-slot virtual comb can exactly reverse a depolarizing channel with one unknown noise parameter out of n+1 potential candidates, and a 1-slot virtual comb can exactly reverse an arbitrary pair of quantum channels.

Win Ratio Analyses of Piperacillin-Tazobactam Versus Meropenem for Ceftriaxone-Nonsusceptible Escherichia coli or Klebsiella pneumoniae Bloodstream Infections: Post Hoc Insights From the MERINO Trial.

Background: Clinical trials of treatments for serious infections commonly use the primary endpoint of all-cause mortality. However, many trial participants survive their infection and this endpoint may not truly reflect important benefits and risks of therapy. The win ratio uses a hierarchical composite endpoint that can incorporate and prioritize outcome measures by relative clinical importance.

Individualised, short-course antibiotic treatment versus usual long-course treatment for ventilator-associated pneumonia (REGARD-VAP): a multicentre, individually randomised, open-label, non-inferiority trial.

Background: Ventilator-associated pneumonia (VAP) is associated with increased mortality, prolonged hospitalisation, excessive antibiotic use and, consequently, increased antimicrobial resistance. In this phase 4, randomised trial, we aimed to establish whether a pragmatic, individualised, short-course antibiotic treatment strategy for VAP was non-inferior to usual care.

Methods: We did an individually randomised, open-label, hierarchical non-inferiority-superiority trial in 39 intensive care units in six hospitals in Nepal, Singapore, and Thailand.

Super-Resolution Reconstruction of CT Images Based on Multi-scale Information Fused Generative Adversarial Networks.

The popularization and widespread use of computed tomography (CT) in the field of medicine evocated public attention to the potential radiation exposure endured by patients. Reducing the radiation dose may lead to scattering noise and low resolution, which can adversely affect the radiologists' judgment. Hence, this paper introduces a new network called PANet-UP-ESRGAN (PAUP-ESRGAN), specifically designed to obtain low-dose CT (LDCT) images with high peak signal-to-noise ratio (PSNR) and high resolution (HR).

The burden and dynamics of hospital-acquired SARS-CoV-2 in England.

Hospital-based transmission had a dominant role in Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV) epidemics, but large-scale studies of its role in the SARS-CoV-2 pandemic are lacking. Such transmission risks spreading the virus to the most vulnerable individuals and can have wider-scale impacts through hospital-community interactions. Using data from acute hospitals in England, we quantify within-hospital transmission, evaluate likely pathways of spread and factors associated with heightened transmission risk, and explore the wider dynamical consequences.

Risk factors for SARS-CoV-2 infection among health workers in India: a case control study.

Background: COVID-19 was declared as a Public Health Emergency of International Concern on 30th January 2020. Compared to the general population, healthcare workers and their families have been identified to be at a higher risk of getting infected with COVID-19. Therefore, it is crucial to understand the risk factors responsible for the transmission of SARS-CoV-2 infection among health workers in different hospital settings and to describe the range of clinical presentations of SARS-CoV-2 infection among them.

Implications of reducing antibiotic treatment duration for antimicrobial resistance in hospital settings: A modelling study and meta-analysis.

Background: Reducing antibiotic treatment duration is a key component of hospital antibiotic stewardship interventions. However, its effectiveness in reducing antimicrobial resistance is uncertain and a clear theoretical rationale for the approach is lacking. In this study, we sought to gain a mechanistic understanding of the relation between antibiotic treatment duration and the prevalence of colonisation with antibiotic-resistant bacteria in hospitalised patients.

Infection prevention and control risk factors in health workers infected with SARS-CoV-2 in Jordan: A case control study.

Background: Despite under-reporting, health workers (HWs) accounted for 2 to 30% of the reported COVID-19 cases worldwide. In line with data from other countries, Jordan recorded multiple case surges among HWs.

Methods: Based on the standardized WHO UNITY case-control study protocol on assessing risk factors for SARS-CoV-2 infection in HWs, HWs with confirmed COVID-19 were recruited as cases from eight hospitals in Jordan.

The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.

Background: SARS-CoV-2 is known to transmit in hospital settings, but the contribution of infections acquired in hospitals to the epidemic at a national scale is unknown.

Methods: We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset > 7 days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed.

The potential impact of intensified community hand hygiene interventions on respiratory tract infections: a modelling study.

Hand hygiene is among the most fundamental and widely used behavioural measures to reduce the person-to-person spread of human pathogens and its effectiveness as a community intervention is supported by evidence from randomized trials. However, a theoretical understanding of the relationship between hand hygiene frequency and change in risk of infection is lacking. Using a simple model-based framework for understanding the determinants of hand hygiene effectiveness in preventing viral respiratory tract infections, we show that a crucial, but overlooked, determinant of the relationship between hand hygiene frequency and risk of infection via indirect transmission is persistence of viable virus on hands.

The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020.

SARS-CoV-2 is known to transmit in hospital settings, but the contribution of infections acquired in hospitals to the epidemic at a national scale is unknown. We used comprehensive national English datasets to determine the number of COVID-19 patients with identified hospital-acquired infections (with symptom onset >7 days after admission and before discharge) in acute English hospitals up to August 2020. As patients may leave the hospital prior to detection of infection or have rapid symptom onset, we combined measures of the length of stay and the incubation period distribution to estimate how many hospital-acquired infections may have been missed.