Antibiotic prescribing for care-home residents: a population-based, cross-classified multilevel analysis in Scotland, UK.

Background: There is wide variation in antibiotic prescribing across care-homes for older people, with implications for resident outcomes and antimicrobial resistance.

Objective: To quantify variation in antibiotic prescribing and associations with resident, care-home and general practice characteristics.

Design: Population-based analyses using administrative data.

Patients' and Clinicians' Experiences Using a Real-Time Remote Monitoring System for Chemotherapy Symptom Management (ASyMS): Qualitative Study.

Background: Patients receiving chemotherapy require ongoing symptom monitoring and management to optimize their outcomes. In recent years, digital remote monitoring interventions have emerged to provide enhanced cancer care delivery experiences to patients and clinicians. However, patient and clinician experiential evaluations of these technologies are rare.

iDiabetes platform-enhanced phenotyping of patients with diabetes for precision diagnosis, prognosis and treatment: study protocol for a cluster-randomised controlled study in Tayside, Scotland.

Introduction And Aim: Diabetes is a global health emergency with increasing prevalence and diabetes-associated morbidity and mortality. One of the challenges in optimising diabetes care is translating research advances in this heterogeneous disease into clinical care. A potential solution is the introduction of precision medicine approaches into diabetes care.

Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass: Findings from the LACE sarcopenia trial.

Introduction: Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor.

Patients' and Clinicians' Perceptions of the Clinical Utility of Predictive Risk Models for Chemotherapy-Related Symptom Management: Qualitative Exploration Using Focus Groups and Interviews.

Background: Interest in the application of predictive risk models (PRMs) in health care to identify people most likely to experience disease and treatment-related complications is increasing. In cancer care, these techniques are focused primarily on the prediction of survival or life-threatening toxicities (eg, febrile neutropenia). Fewer studies focus on the use of PRMs for symptoms or supportive care needs.

Community antibiotic prescribing in patients with COVID-19 across three pandemic waves: a population-based study in Scotland, UK.

Objectives: This study aims to examine community antibiotic prescribing across a complete geographical area for people with a positive COVID-19 test across three pandemic waves, and to examine health and demographic factors associated with antibiotic prescribing.

Design: A population-based study using administrative data.

Setting: A complete geographical region within Scotland, UK.

The implications of competing risks and direct treatment disutility in cardiovascular disease and osteoporotic fracture: risk prediction and cost effectiveness analysis.

Background: Clinical guidelines commonly recommend preventative treatments for people above a risk threshold. Therefore, decision-makers must have faith in risk prediction tools and model-based cost-effectiveness analyses for people at different levels of risk. Two problems that arise are inadequate handling of competing risks of death and failing to account for direct treatment disutility (i.

Age and cancer type: associations with increased odds of receiving a late diagnosis in people with advanced cancer.

Purpose: In order to deliver appropriate and timely care planning and minimise avoidable late diagnoses, clinicians need to be aware of which patients are at higher risk of receiving a late cancer diagnosis. We aimed to determine which demographic and clinical factors are associated with receiving a 'late' cancer diagnosis (within the last 12 weeks of life).

Method: Retrospective cohort study of 2,443 people who died from cancer ('cancer decedents') in 2013-2015.

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.

Background: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.

ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial.

Background: Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result.

Quantifying the impact of taking medicines for primary prevention: a time-trade off study to elicit direct treatment disutility in the UK.

Background: Direct treatment disutility (DTD) represents an individual's disutility associated with the inconvenience of taking medicine over a long period of time.

Objectives: The main aim of this study was to elicit DTD values for taking a statin or a bisphosphonate for primary prevention. A secondary aim was to understand factors which influence DTD values.

Custom tuning of Rieske oxygenase reactivity.

Rieske oxygenases use a Rieske-type [2Fe-2S] cluster and a mononuclear iron center to initiate a range of chemical transformations. However, few details exist regarding how this catalytic scaffold can be predictively tuned to catalyze divergent reactions. Therefore, in this work, using a combination of structural analyses, as well as substrate and rational protein-based engineering campaigns, we elucidate the architectural trends that govern catalytic outcome in the Rieske monooxygenase TsaM.

The NADH recycling enzymes TsaC and TsaD regenerate reducing equivalents for Rieske oxygenase chemistry.

Many microorganisms use both biological and nonbiological molecules as sources of carbon and energy. This resourcefulness means that some microorganisms have mechanisms to assimilate pollutants found in the environment. One such organism is Comamonas testosteroni, which metabolizes 4-methylbenzenesulfonate and 4-methylbenzoate using the TsaMBCD pathway.

Multicenter Randomized Trial Assessing MRI and Image-guided Biopsy for Suspected Prostate Cancer: The MULTIPROS Study.

Background The optimal diagnostic pathway for prostate cancer (PCa) is evolving, requiring further evaluation in a randomized controlled trial. Purpose To assess the diagnostic accuracy of prebiopsy multiparametric MRI in the identification of clinically significant PCa (csPCa) using radical prostatectomy (RP) specimens as the reference standard, and to test the diagnostic accuracy of combined US and MRI fusion-targeted biopsy with systematic biopsies. Materials and Methods In a prospective randomized controlled trial including university hospitals, men with suspected PCa were recruited between January 2015 and August 2020 to assess the diagnostic accuracy of multiparametric MRI before biopsy in detection of csPCa at biopsy and RP histopathologic structure (primary outcome).

Leveraging a Structural Blueprint to Rationally Engineer the Rieske Oxygenase TsaM.

Rieske nonheme iron oxygenases use two metallocenters, a Rieske-type [2Fe-2S] cluster and a mononuclear iron center, to catalyze oxidation reactions on a broad range of substrates. These enzymes are widely used by microorganisms to degrade environmental pollutants and to build complexity in a myriad of biosynthetic pathways that are industrially interesting. However, despite the value of this chemistry, there is a dearth of understanding regarding the structure-function relationships in this enzyme class, which limits our ability to rationally redesign, optimize, and ultimately exploit the chemistry of these enzymes.

External validation of the QLifetime cardiovascular risk prediction tool: population cohort study.

Background: Prediction of lifetime cardiovascular disease (CVD) risk is recommended in many clinical guidelines, but lifetime risk models are rarely externally validated. The aim of this study was to externally validate the QRiskLifetime incident CVD risk prediction tool.

Methods: Independent external validation of QRiskLifetime using Clinical Practice Research Datalink data, examining discrimination and calibration in the whole population and stratified by age, and reclassification compared to QRISK3.

Effect of competing mortality risks on predictive performance of the QFracture risk prediction tool for major osteoporotic fracture and hip fracture: external validation cohort study in a UK primary care population.

Objective: To externally evaluate the QFracture risk prediction tool for predicting the risk of major osteoporotic fracture and hip fracture.

Design: External validation cohort study.

Setting: UK primary care population.

A structure-function analysis of chlorophyllase reveals a mechanism for activity regulation dependent on disulfide bonds.

Chlorophyll pigments are used by photosynthetic organisms to facilitate light capture and mediate the conversion of sunlight into chemical energy. Due to the indispensable nature of this pigment and its propensity to form reactive oxygen species, organisms heavily invest in its biosynthesis, recycling, and degradation. One key enzyme implicated in these processes is chlorophyllase, an α/β hydrolase that hydrolyzes the phytol tail of chlorophyll pigments to produce chlorophyllide molecules.

Free-text analysis of general practice out-of-hours (GPOOH) use by people with advanced cancer: an analysis of coded and uncoded free-text data.

Background: People with advanced cancer frequently use the GP out-of-hours (GPOOH) service. Considerable amounts of routine GPOOH data are uncoded. Therefore, these data are omitted from existing healthcare datasets.

Derivation and validation of the CFracture competing risk fracture prediction tool compared with QFracture in older people and people with comorbidity: a population cohort study.

Background: UK guidelines recommend the QFracture tool to predict the risk of major osteoporotic fracture and hip fracture, but QFracture calibration is poor, partly because it does not account for competing mortality risk. The aim of this study was to derive and validate a competing risk model to predict major osteoporotic fracture and hip fracture (CFracture) and compare its performance with that of QFracture in UK primary care.

Methods: We used UK linked primary care data from the Clinical Practice Research Datalink GOLD database to identify people aged 30-99 years, split into derivation and validation cohorts.

Patient outcomes following AKI and AKD: a population-based cohort study.

Background: Acute kidney injury (AKI) is common and associated with adverse outcomes as well as important healthcare costs. However, evidence examining the epidemiology of acute kidney disease (AKD)-recently defined as AKI persisting between 7 and 90 days-remains limited. The aims of this study were to establish the rates of early AKI recovery, progression to AKD and non-recovery; examine risk factors associated with non-recovery and investigate the association between recovery timing and adverse outcomes, in a population-based cohort.

Community prescribing trends and prevalence in the last year of life, for people who die from cancer.

Background: People who die from cancer ('cancer decedents') may latterly experience unpleasant and distressing symptoms. Prescribing medication for pain and symptom control is essential for good-quality palliative care; however, such provision is variable, difficult to quantify and poorly characterised in current literature. This study aims to characterise trends in prescribing analgesia, non-analgesic palliative care medication and non-palliative medications, to cancer decedents, in their last year of life, and to assess any associations with demographic or clinical factors.

Predictive performance of a competing risk cardiovascular prediction tool CRISK compared to QRISK3 in older people and those with comorbidity: population cohort study.

Background: Recommended cardiovascular disease (CVD) prediction tools do not account for competing mortality risk and over-predict incident CVD in older and multimorbid people. The aim of this study was to derive and validate a competing risk model (CRISK) to predict incident CVD and compare its performance to that of QRISK3 in UK primary care.

Methods: We used UK linked primary care data from the Clinical Practice Research Datalink (CPRD) GOLD to identify people aged 25-84 years with no previous CVD or statin treatment split into derivation and validation cohorts.

Death from cancer: frequent unscheduled care.

Objective: To examine the demographic, clinical, and temporal factors associated with cancer decedents being a frequent or very frequent unscheduled care (GP-general practice Out-Of-Hours (GPOOH) and Accident & Emergency (A&E)) attender, in their last year of life.

Methods: Retrospective cohort study, of all 2443 cancer decedents in Tayside, Scotland, over 30- months period up to 06/2015, comparing frequent attenders (5-9 attendances/year) and very frequent attenders (≥10 attendances/year) to infrequent attenders (1-4 attendances/year) and non-attenders. Clinical and demographic datasets were linked to routinely-collected clinical data using the Community Health Index number.