An objective measure of response on whole-body MRI in metastatic hormone sensitive prostate cancer treated with androgen deprivation therapy, external beam radiotherapy, and radium-223.

Objectives: The aim of this study was to generate an objective method to describe MRI data to assess response in the vertebrae of patients with metastatic hormone sensitive prostate cancer (mHSPC), treated with external beam radiation therapy and systemic therapy with Radium-223 and to correlate changes with clinical outcomes.

Methods: Three sets of whole-body MRI (WBMRI) images were utilized from 25 patients from the neo-adjuvant Androgen Deprivation Therapy pelvic Radiotherapy and RADium-223 (ADRRAD) clinical trial: MRI1 (up to 28 days before Radium-223), MRI2, and MRI3 (2 and 6 months post completion of Radium-223). Radiological response was assessed based on post baseline MRI images.

Infections diagnosed in children and young people screened for malaria in UK emergency departments: a retrospective multi-centre study.

Background: Data on imported infections in children and young people (CYP) are sparse.

Aims: To describe imported infections in CYP arriving from malaria-endemic areas and presenting to UK emergency departments (ED) who were screened for malaria.

Methods: This is a retrospective, multi-centre, observational study nested in a diagnostic accuracy study for malaria rapid diagnostic tests.

OpenMM 8: Molecular Dynamics Simulation with Machine Learning Potentials.

Machine learning plays an important and growing role in molecular simulation. The newest version of the OpenMM molecular dynamics toolkit introduces new features to support the use of machine learning potentials. Arbitrary PyTorch models can be added to a simulation and used to compute forces and energy.

Urine tenofovir and dried blood spot tenofovir diphosphate concentrations and viraemia in people taking efavirenz and dolutegravir-based antiretroviral therapy.

Objective: We aimed to determine whether urine tenofovir (TFV) and dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations are associated with concurrent HIV viraemia.

Design: Cross-sectional study among people with HIV (PWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART).

Methods: We used dual tandem liquid chromatography and mass spectrometry to measure urine TFV and DBS TFV-DP concentrations, and evaluated their associations with concurrent viraemia at least 1000 copies/ml using logistic regression models.

What are important areas where better technology would support women's health? Findings from a priority setting partnership.

Background: Women's health has historically lacked investment in research and development. Technologies that enhance women's health ('FemTech') could contribute to improving this. However, there has been little work to understand which priority unmet needs should be a focus for women's health technology development.

OpenMM 8: Molecular Dynamics Simulation with Machine Learning Potentials.

Machine learning plays an important and growing role in molecular simulation. The newest version of the OpenMM molecular dynamics toolkit introduces new features to support the use of machine learning potentials. Arbitrary PyTorch models can be added to a simulation and used to compute forces and energy.

Evaluation of the diagnostic accuracy of two point-of-care tests for COVID-19 when used in symptomatic patients in community settings in the UK primary care COVID diagnostic accuracy platform trial (RAPTOR-C19).

Background And Objective: Point-of-care lateral flow device antigen testing has been used extensively to identify individuals with active SARS-CoV-2 infection in the community. This study aimed to evaluate the diagnostic accuracy of two point-of-care tests (POCTs) for SARS-CoV-2 in routine community care.

Methods: Adults and children with symptoms consistent with suspected current COVID-19 infection were prospectively recruited from 19 UK general practices and two COVID-19 testing centres between October 2020 and October 2021.

A Diagnostic Accuracy Study to Evaluate Standard Rapid Diagnostic Test (RDT) Alone to Safely Rule Out Imported Malaria in Children Presenting to UK Emergency Departments.

Background: Microscopy is the gold standard for malaria diagnosis but is dependent on trained personnel. Rapid diagnostic tests (RDTs) form the mainstay of diagnosis in endemic areas without access to high-quality microscopy. We aimed to evaluate whether RDT alone could rule out imported malaria in children presenting to UK emergency departments (EDs).

A Randomized Trial of Autologous Chondrocyte Implantation Versus Alternative Forms of Surgical Cartilage Management in Patients With a Failed Primary Treatment for Chondral or Osteochondral Defects in the Knee.

Background: There are limited randomized controlled trials with long-term outcomes comparing autologous chondrocyte implantation (ACI) versus alternative forms of surgical cartilage management within the knee.

Purpose: To determine at 5 years after surgery whether ACI was superior to alternative forms of cartilage management in patients after a failed previous treatment for chondral or osteochondral defects in the knee.

Study Design: Randomized controlled trial; Level of evidence, 1.

The Impact of Point-of-Care Blood C-Reactive Protein Testing on Prescribing Antibiotics in Out-of-Hours Primary Care: A Mixed Methods Evaluation.

Improving prescribing antibiotics appropriately for respiratory infections in primary care is an antimicrobial stewardship priority. There is limited evidence to support interventions to reduce prescribing antibiotics in out-of-hours (OOH) primary care. Herein, we report a service innovation where point-of-care C-Reactive Protein (CRP) machines were introduced to three out-of-hours primary care clinical bases in England from August 2018-December 2019, which were compared with four control bases that did not have point-of-care CRP testing.

Lack of influence of dexmedetomidine on rat glomus cell response to hypoxia, and on mouse acute hypoxic ventilatory response.

Background And Aims: There is a lack of basic science data on the effect of dexmedetomidine on the hypoxic chemosensory reflex with both depression and stimulation suggested. The primary aim of this study was to assess if dexmedetomidine inhibited the cellular response to hypoxia in rat carotid body glomus cells, the cells of the organs mediating acute hypoxic ventilatory response (AHVR). Additionally, we used a small sample of mice to assess if there was any large influence of subsedative doses of dexmedetomidine on AHVR.

The comparative interrupted time series design for assessment of diagnostic impact: methodological considerations and an example using point-of-care C-reactive protein testing.

Background: In diagnostic evaluation, it is necessary to assess the clinical impact of a new diagnostic as well as its diagnostic accuracy. The comparative interrupted time series design has been proposed as a quasi-experimental approach to evaluating interventions. We show how it can be used in the design of a study to evaluate a point-of-care diagnostic test for C-reactive protein in out-of-hours primary care services, to guide antibiotic prescribing among patients presenting with possible respiratory tract infection.

Dose estimation after a mixed field exposure: Radium-223 and intensity modulated radiotherapy.

Introduction: Radium-223 dichloride ([Ra]RaCl), a radiopharmaceutical that delivers α-particles to regions of bone metastatic disease, has been proven to improve overall survival of men with metastatic castration resistant prostate cancer (mCRPC). mCRPC patients enrolled on the ADRRAD clinical trial are treated with a mixed field exposure comprising radium-223 (Ra) and intensity modulated radiotherapy (IMRT). While absorbed dose estimation is an important step in the characterisation of wider systemic radiation risks in nuclear medicine, uncertainties remain for novel radiopharmaceuticals such as Ra.

BSAC Vanguard Series: Antimicrobial resistance and the future of diagnostic testing.

In the UK around 80% of all antibiotics are prescribed by GP surgeries and in other community settings. Diagnostic technology has the potential to enable transformative change to antimicrobial stewardship in these settings. Current diagnostics are limited in terms of the information they can provide prescribers and the speed they can provide it.

Toxicity and Efficacy of Concurrent Androgen Deprivation Therapy, Pelvic Radiotherapy, and Radium-223 in Patients with Metastatic Hormone-Sensitive Prostate Cancer.

Purpose: Radium-223 is an alpha-emitting radionuclide associated with overall survival (OS) improvement in metastatic castration-resistant prostate cancer (mCRPC). External beam radiotherapy (EBRT) to prostate extends OS in men with metastatic hormone-sensitive prostate cancer (mHSPC) limited to less than 4 metastases. We hypothesized that combination radium-223 + pelvic EBRT could safely deliver maximal radiotherapy doses to primary and metastatic prostate cancer and may improve disease control.

Rapid community point-of-care testing for COVID-19 (RAPTOR-C19): protocol for a platform diagnostic study.

Background: The aim of RApid community Point-of-care Testing fOR COVID-19 (RAPTOR-C19) is to assess the diagnostic accuracy of multiple current and emerging point-of-care tests (POCTs) for active and past SARS-CoV2 infection in the community setting. RAPTOR-C19 will provide the community testbed to the COVID-19 National DiagnOstic Research and Evaluation Platform (CONDOR).

Methods: RAPTOR-C19 incorporates a series of prospective observational parallel diagnostic accuracy studies of SARS-CoV2 POCTs against laboratory and composite reference standards in patients with suspected current or past SARS-CoV2 infection attending community settings.

At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data.

Background: Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity.

Methods: We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases.

Competitive Interactions between Halothane and Isoflurane at the Carotid Body and TASK Channels.

Background: The degree to which different volatile anesthetics depress carotid body hypoxic response relates to their ability to activate TASK potassium channels. Most commonly, volatile anesthetic pairs act additively at their molecular targets. We examined whether this applied to carotid body TASK channels.

In-vitro diagnostic point-of-care tests in paediatric ambulatory care: A systematic review and meta-analysis.

Introduction: Paediatric consultations form a significant proportion of all consultations in ambulatory care. Point-of-care tests (POCTs) may offer a potential solution to improve clinical outcomes for children by reducing diagnostic uncertainty in acute illness, and streamlining management of chronic diseases. However, their clinical impact in paediatric ambulatory care is unknown.

Implementation of Physical Employment Standards for Physically Demanding Occupations.

Objective: The aim of this paper was to describe an approach to implementing and integrating physical employment standards into an organizational procedure, to ensure the safe and effective supervision of physical fitness of workers in a physically demanding occupation, using a real-world example.

Methods: Using previously published cardiorespiratory, muscular strength, and endurance physical demands data from UK firefighters, a process to manage all levels of physical capability was developed with industry stakeholders.

Results: Performance standards and associated cut-scores relating to acceptable, uncertain, and unacceptable job performance, using a traffic-light style process, were agreed by stakeholders to ensure the safe and effective management of incumbent's physical fitness.

Impact of point-of-care panel tests in ambulatory care: a systematic review and meta-analysis.

Objectives: This article summarises all the available evidence on the impact of introducing blood-based point-of-care panel testing (POCT) in ambulatory care on patient outcomes and healthcare processes.

Design: Systematic review and meta-analysis of randomised-controlled trials and before-after studies.

Data Sources: Ovid Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane CENTRAL, Database of Abstracts of Reviews and Effects, Science Citation Index from inception to 22 October 2019.

Pre-analytical error for three point of care venous blood testing platforms in acute ambulatory settings: A mixed methods service evaluation.

Introduction: Point of care blood testing to aid diagnosis is becoming increasingly common in acute ambulatory settings and enables timely investigation of a range of diagnostic markers. However, this testing allows scope for errors in the pre-analytical phase, which depends on the operator handling and transferring specimens correctly. The extent and nature of these pre-analytical errors in clinical settings has not been widely reported.