Race and ethnicity in the COVID-19 Critical Care Consortium: demographics, treatments, and outcomes, an international observational registry study.

BACKGROUND: Improving access to healthcare for ethnic minorities is a public health priority in many countries, yet little is known about how to incorporate information on race, ethnicity, and related social determinants of health into large international studies. Most studies of differences in treatments and outcomes of COVID-19 associated with race and ethnicity are from single cities or countries. METHODS: We present the breadth of race and ethnicity reported for patients in the COVID-19 Critical Care Consortium, an international observational cohort study from 380 sites across 32 countries. Patients from the United States, Australia, and South Africa were the focus of an analysis of treatments and in-hospital mortality stratified by race and ethnicity. Inclusion criteria were admission to intensive care for acute COVID-19 between January 14th, 2020, and February 15, 2022. Measurements included demographics, comorbidities, disease severity scores, treatments for organ failure, and in-hospital mortality. RESULTS: Seven thousand three hundred ninety-four adults met the inclusion criteria. There was a wide variety of race and ethnicity designations. In the US, American Indian or Alaska Natives frequently received dialysis and mechanical ventilation and had the highest mortality. In Australia, organ failure scores were highest for Aboriginal/First Nations persons. The South Africa cohort ethnicities were predominantly Black African (50%) and Coloured* (28%). All patients in the South Africa cohort required mechanical ventilation. Mortality was highest for South Africa (68%), lowest for Australia (15%), and 30% in the US. CONCLUSIONS: Disease severity was higher for Indigenous ethnicity groups in the US and Australia than for other ethnicities. Race and ethnicity groups with longstanding healthcare disparities were found to have high acuity from COVID-19 and high mortality. Because there is no global system of race and ethnicity classification, researchers designing case report forms for international studies should consider including related information, such as socioeconomic status or migration background. *Note: "Coloured" is an official, contemporary government census category of South Africa and is a term of self-identification of race and ethnicity of many citizens of South Africa.

Oligonucleotide and polymer functionalized nanoparticles for amplification-free detection of DNA.

Sensitive and quantitative nucleic acid testing from complex biological samples is now an important component of clinical diagnostics. Whereas nucleic acid amplification represents the gold standard, its utility in resource-limited and point-of-care settings can be problematic due to assay interferants, assay time, engineering constraints, and costs associated with both wetware and hardware. In contrast, amplification-free nucleic acid testing can circumvent these limitations by enabling direct target hybridization within complex sample matrices. In this work, we grew random copolymer brushes from the surface of silica-coated magnetic nanoparticles using azide-modified and hydroxyl oligo ethylene glycol methacrylate (OEGMA) monomers. The azide-functionalized polymer brush was first conjugated, via copper-catalyzed azide/alkyne cycloaddition (CuAAC), with herpes simplex virus (HSV)-specific oligonucleotides and then with alkyne-substituted polyethylene glycol to eliminate all residual azide groups. Our methodology enabled control over brush thickness and probe density and enabled multiple consecutive coupling reactions on the particle grafted brush. Brush- and probe-modified particles were then combined in a 20 min hybridization with fluorescent polystyrene nanoparticles modified with HSV-specific reporter probes. Following magnetic capture and washing, the particles were analyzed with an aggregate fluorescence measurement, which yielded a limit of detection of 6 pM in buffer and 60 pM in 50% fetal bovine serum. Adoption of brush- and probe-modified particles into a particle counting assay will result in the development of diagnostic assays with significant improvements in sensitivity.

Amplification free detection of herpes simplex virus DNA.

Amplification-free detection of nucleic acids in complex biological samples is an important technology for clinical diagnostics, especially in the case where the detection is quantitative and highly sensitive. Here we present the detection of a synthetic DNA sequence from Herpes Simplex Virus-1 within swine cerebrospinal fluid (CSF), using a sandwich-like, magnetic nanoparticle pull-down assay. Magnetic nanoparticles and fluorescent polystyrene nanoparticles were both modified with DNA probes, able to hybridise either end of the target DNA, forming the sandwich-like complex which can be captured magnetically and detected by fluorescence. The concentration of the target DNA was determined by counting individual and aggregated fluorescent nanoparticles on a planar glass surface within a fluidic chamber. DNA probe coupling for both nanoparticles was optimized. Polystyrene reporter nanoparticles that had been modified with amine terminated DNA probes were also treated with amine terminated polyethylene glycol, in order to reduce non-specific aggregation and target independent adhesion to the magnetic particles. This way, a limit of detection for the target DNA of 0.8 pM and 1 pM could be achieved for hybridisation buffer and CSF respectively, corresponding to 0.072 and 0.090 femtomoles of target DNA, in a volume of 0.090 mL.

The role of endoscopic retrograde pancreatography in pancreatic trauma: a critical appraisal of 48 patients treated at a tertiary institution.

BACKGROUND: Endoscopic retrograde pancreatography (ERP) is useful in the diagnosis and treatment of selected patients with pancreatic trauma. We analyzed the role of ERP in treating persistent complications of pancreatic injuries at a tertiary institution. METHODS: Patients with pancreatic trauma who underwent ERP were identified from a prospective database of 426 pancreatic injuries from January 1983 to January 2011. Patient demographics, mechanism of injury, time to presentation, method of diagnosis, associated injuries, clinical management, endoscopic interventions and their timing, surgical treatment, and patient outcomes were evaluated. RESULTS: Forty-eight patients underwent ERP after blunt (n = 26) or penetrating (n = 22) pancreatic injury. Median time from injury to ERP was 38 days (range, 2-365 days). Diagnostic ERP was successful in 47 patients. In 11 patients, ERP demonstrated an intact main duct with minor peripheral injuries, and no further intervention was required. A pancreatic fistula was demonstrated in 24, a main pancreatic duct stricture in 12, and a pseudocyst in 10 patients. Fifteen patients had a pancreatic duct sphincterotomy, seven had a pancreatic stent inserted, and six had an endoscopic pseudocyst drainage. Ten patients ultimately required surgery, seven of whom had demonstrated a severe pancreatic duct stricture. Operations performed following ERP were distal pancreatectomy (n = 6), pancreaticojejunostomy (n = 3) and cyst-jejunostomy (n = 1). CONCLUSION: ERP allowed one quarter of the patients to be treated conservatively. Half had a successful intervention by ERP. Success was most likely in those with fistulae and pseudocysts. Surgery was ultimately avoided in more than three quarters of the patients. LEVEL OF EVIDENCE: Therapeutic study, level V.

A paramagnetic-reporter two-particle system for amplification-free detection of DNA in serum.

Quantitative nucleic acid detection is used extensively in the management of many pathogenic infections, where viral or bacterial nucleic acid copy number relates directly to disease prognosis. Temperature-cycle or isothermal amplification formats offer excellent performance, but their requirement for purified nucleic acid and accurate temperature control increases costs and renders their migration to resource-limited environments problematic. In contrast, amplification-free nucleic acid assays could allow simplified system design, resulting in reduced costs. In this study, we report a amplification-free herpes simplex virus (HSV) assay where oligoethylene glycol methacrylate (OEGMA) grafted ssDNA capture-probes on paramagnetic nanoparticles are coupled with reporter-probe-modified fluorescent nanoparticles in a target-dependent manner. Following assay and reagent optimization, a sub-pM (25 amol) limit of detection could be achieved in buffer and also in neat, undiluted serum, representing a 160-fold improvement over that achieved using convention detection with a fluorescence plate reader. Equivalent performance in serum and buffer offers the opportunity for simplified diagnostic device design for resource-limited environments.

Antibiotic treatment of urinary tract infection by community pharmacists: a cross-sectional study.

BACKGROUND: Urinary tract infections (UTIs) are one of the most common conditions seen in female patients within primary care. Community pharmacists are familiar with symptomatic UTI management and supplying trimethoprim under patient group direction (PGD) for moderate-to-severe uncomplicated UTIs could improve patient access to treatment. AIM: To compare the care pathway of patients with UTI symptoms attending GP services with those receiving management, including trimethoprim supply under PGD, via community pharmacies. DESIGN AND SETTING: Prospective, cross-sectional, mixed methods approach in 10 community pharmacies within NHS Greater Glasgow and Clyde. METHOD: Pharmacies invited a purposive sample of female patients to participate. Pharmacists had the option of supplying trimethoprim under PGD to patients with moderate-to-severe infection meeting the PGD inclusion criteria. Data from patient (questionnaires and semi-structured telephone interviews) and pharmacist (questionnaires and semi-structured, face-to-face interviews) were quantitatively and qualitatively analysed. RESULTS: Data were recorded on 153 patients, 97 presenting with GP prescriptions and 56 presenting directly in the pharmacy with symptoms suggestive of UTI, of whom 41 received trimethoprim via PGD and 15 received symptomatic management. Both GP adherence to local infection management guidelines and pharmacist application of PGD inclusion/exclusion criteria required improvement. There was demand and support, from patients and pharmacists, for access to antibiotic treatments for UTIs, without prescription, through community pharmacies. CONCLUSION: Operating within PGD controls, antibiotic treatments for UTIs could be provided via community pharmacy to improve patient access to treatment which may also maintain antibiotic stewardship and reduce GP workload.