Lockdown Britain: Evidence for reduced incidence and severity of some non-COVID acute medical illnesses.

Large reductions in emergency department attendances and hospitalisations with non-COVID acute medical illness early during the pandemic were attributed to reluctance to seek medical help and higher referral thresholds. Here, we compare acute medical admissions with a comparison cohort from 2017. Deaths in the same geographic area were examined, and Wales-wide deaths during these 4 weeks in 2020 were compared with a seasonally matched period in 2019. There were 528 patients admitted with non-COVID illness in 2020, versus 924 in 2017 (a reduction of 43%). Deaths from non-COVID causes increased by 10.9% compared with 2017, over half this rise being from neurological causes including stroke and dementia. While far fewer patients required hospitalisation as medical emergencies, rises in local non-COVID deaths proved small. Wales-wide non-COVID deaths rose by just 1% compared with 2019. The findings suggest that changes in population behaviour and lifestyle during lockdown brought about unforeseen health benefits.

Tracking Yeast Metabolism and the Crabtree Effect in Real Time via CO2 Production using Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS).

In this study, a new approach to measure metabolic activity of yeast via the Crabtree effect is described. BARDS is an analytical technique developed to aid powder and tablet characterisation by monitoring changes in the compressibility of a solvent during solute dissolution. It is a rapid and simple method which utilises a magnetic stir bar to mix added solute and induce the acoustic resonance of a vessel containing a fixed volume of solvent. In this study it is shown that initiation of fermentation in a yeast suspension, in aqueous buffer, is accompanied by reproducible changes in the frequency of induced acoustic resonance. These changes signify increased compressibility of the suspension due to CO2 release by the yeast. A simple standardised BARDS protocol reveals yeast carbon source preferences and can generate quantitative kinetic data on carbon source metabolism which are characteristic of each yeast strain. The Crawford-Woods equation can be used to quantify total gaseous CO2 produced by a given number of viable yeast when supplied with a fixed amount of carbon source. This allows for a value to be calculated for the amount of gaseous CO2 produced by each yeast cell. The approach has the potential to transform the way in which yeast metabolism is tracked and potentially provide an orthogonal or surrogate method to determining viability, vitality and attenuation measurements in the future.

Real World Patterns of Antimicrobial Use and Microbiology Investigations in Patients with Sepsis outside the Critical Care Unit: Secondary Analysis of Three Nation-Wide Point Prevalence Studies.

Recent description of the microbiology of sepsis on the wards or information on the real-life antibiotic choices used in sepsis is lacking. There is growing concern of the indiscriminate use of antibiotics and omission of microbiological investigations in the management of septic patients. We performed a secondary analysis of three annual 24-h point-prevalence studies on the general wards across all Welsh acute hospitals in years 2016-2018. Data were collected on patient demographics, as well as radiological, laboratory and microbiological data within 48-h of the study. We screened 19,453 patients over the three 24 h study periods and recruited 1252 patients who fulfilled the entry criteria. 775 (64.9%) patients were treated with intravenous antibiotics. Only in 33.65% (421/1252) of all recruited patients did healthcare providers obtain blood cultures; in 25.64% (321/1252) urine cultures; in 8.63% (108/1252) sputum cultures; in 6.79% (85/1252) wound cultures; in 15.25% (191/1252) other cultures. Out of the recruited patients, 59.1% (740/1252) fulfilled SEPSIS-3 criteria. Patients with SEPSIS-3 criteria were significantly more likely to receive antibiotics than the non-septic cohort (p < 0.0001). In a multivariable regression analysis increase in SOFA score, increased number of SIRS criteria and the use of the official sepsis screening tool were associated with antibiotic administration, however obtaining microbiology cultures was not. Our study shows that antibiotics prescription practice is not accompanied by microbiological investigations. A significant proportion of sepsis patients are still at risk of not receiving appropriate antibiotics treatment and microbiological investigations; this may be improved by a more thorough implementation of sepsis screening tools.

Red-flag sepsis and SOFA identifies different patient population at risk of sepsis-related deaths on the general ward.

Controversy exists regarding the best diagnostic and screening tool for sepsis outside the intensive care unit (ICU). Sequential organ failure assessment (SOFA) score has been shown to be superior to systemic inflammatory response syndrome (SIRS) criteria, however, the performance of "Red Flag sepsis criteria" has not been tested formally.The aim of the study was to investigate the ability of Red Flag sepsis criteria to identify the patients at high risk of sepsis-related death in comparison to SOFA based sepsis criteria. We also investigated the comparison of Red Flag sepsis to quick SOFA (qSOFA), SIRS, and national early warning score (NEWS) scores and factors influencing patient mortality.Patients were recruited into a 24-hour point-prevalence study on the general wards and emergency departments across all Welsh acute hospitals. Inclusion criteria were: clinical suspicion of infection and NEWS 3 or above in-line with established escalation criteria in Wales. Data on Red Flag sepsis and SOFA criteria was collected together with qSOFA and SIRS scores and 90-day mortality.459 patients were recruited over a 24-hour period. 246 were positive for Red Flag sepsis, mortality 33.7% (83/246); 241 for SOFA based sepsis criteria, mortality 39.4% (95/241); 54 for qSOFA, mortality 57.4% (31/54), and 268 for SIRS, mortality 33.6% (90/268). 55 patients were not picked up by any criteria. We found that older age was associated with death with OR (95% CI) of 1.03 (1.02-1.04); higher frailty score 1.24 (1.11-1.40); DNA-CPR order 1.74 (1.14-2.65); ceiling of care 1.55 (1.02-2.33); and SOFA score of 2 and above 1.69 (1.16-2.47).The different clinical tools captured different subsets of the at-risk population, with similar sensitivity. SOFA score 2 or above was independently associated with increased risk of death at 90 days. The sequalae of infection-related organ dysfunction cannot be reliably captured based on routine clinical and physiological parameters alone.

Sepsis-related deaths in the at-risk population on the wards: attributable fraction of mortality in a large point-prevalence study.

OBJECTIVE: Sepsis mortality is reported to be high worldwide, however recently the attributable fraction of mortality due to sepsis (AFsepsis) has been questioned. If improvements in treatment options are to be evaluated, it is important to know what proportion of deaths are potentially preventable or modifiable after a sepsis episode. The aim of the study was to establish the fraction of deaths directly related to the sepsis episode on the general wards and emergency departments. RESULTS: 839 patients were recruited over the two 24-h periods in 2016 and 2017. 521 patients fulfilled SEPSIS-3 criteria. 166 patients (32.4%) with sepsis and 56 patients (17.6%) without sepsis died within 90 days. Out of the 166 sepsis deaths 12 (7.2%) could have been directly related to sepsis, 28 (16.9%) possibly related and 96 (57.8%) were not related to sepsis. Overall AFsepsis was 24.1%. Upon analysis of the 40 deaths likely to be attributable to sepsis, we found that 31 patients (77.5%) had the Clinical Frailty Score ≥ 6, 28 (70%) had existing DNA-CPR order and 17 had limitations of care orders (42.5%).

Low-Dimensional Organic Tin Bromide Perovskites and Their Photoinduced Structural Transformation.

Hybrid organic-inorganic metal halide perovskites possess exceptional structural tunability, with three- (3D), two- (2D), one- (1D), and zero-dimensional (0D) structures on the molecular level all possible. While remarkable progress has been realized in perovskite research in recent years, the focus has been mainly on 3D and 2D structures, with 1D and 0D structures significantly underexplored. The synthesis and characterization of a series of low-dimensional organic tin bromide perovskites with 1D and 0D structures is reported. Using the same organic and inorganic components, but at different ratios and reaction conditions, both 1D (C4 N2 H14 )SnBr4 and 0D (C4 N2 H14 Br)4 SnBr6 can be prepared in high yields. Moreover, photoinduced structural transformation from 1D to 0D was investigated experimentally and theoretically in which photodissociation of 1D metal halide chains followed by structural reorganization leads to the formation of a more thermodynamically stable 0D structure.

Phosphorescent Molecular Butterflies with Controlled Potential-Energy Surfaces and Their Application as Luminescent Viscosity Sensor.

We report precise manipulation of the potential-energy surfaces (PESs) of a series of butterfly-like pyrazolate-bridged platinum binuclear complexes, by synthetic control of the electronic structure of the cyclometallating ligand and the steric bulkiness of the pyrazolate bridging ligand. Color tuning of dual emission from blue/red, to green/red and red/deep red were achieved for these phosphorescent molecular butterflies, which have two well-controlled energy minima on the PESs. The environmentally dependent photoluminescence of these molecular butterflies enabled their application as self-referenced luminescent viscosity sensor.

Covalently tethered TGF-ß1 with encapsulated chondrocytes in a PEG hydrogel system enhances extracellular matrix production.

Healing articular cartilage defects remains a significant clinical challenge because of its limited capacity for self-repair. While delivery of autologous chondrocytes to cartilage defects has received growing interest, combining cell-based therapies with growth factor delivery that can locally signal cells and promote their function is often advantageous. We have previously shown that PEG thiol-ene hydrogels permit covalent attachment of growth factors. However, it is not well known if embedded chondrocytes respond to tethered signals over a long period. Here, chondrocytes were encapsulated in PEG hydrogels functionalized with transforming growth factor-beta 1 (TGF-ß1) with the goal of increasing proliferation and matrix production. Tethered TGF-ß1 was found to be distributed homogenously throughout the gel, and its bioactivity was confirmed with a TGF-ß1 responsive reporter cell line. Relative to solubly delivered TGF-ß1, chondrocytes presented with immobilized TGF-ß1 showed significantly increased DNA content, and GAG and collagen production over 28 days, while maintaining markers of articular cartilage. These results indicate the potential of thiol-ene chemistry to covalently conjugate TGF-ß1 to PEG to locally influence chondrocyte function over 4 weeks. Scaffolds with other or multiple tethered growth factors may prove broadly useful in the design of chondrocyte delivery vehicles for cartilage tissue engineering applications.