COVID-19 mortality in the UK Biobank cohort: revisiting and evaluating risk factors

European Journal of Epidemiology - Most studies of severe/fatal COVID-19 risk have used routine/hospitalisation data without detailed pre-morbid characterisation. Using the community-based UK...     

GAG-augmented polysaccharide hydrogel: a novel biocompatible and biodegradable material to support chondrogenesis

The quality of articular cartilage engineered using a cell-polymer construct depends, in part, on the chemical composition of the biomaterial and whether that biomaterial can support the chondrocytic phenotype. Acknowledging the supportive influence of tissue-specific matrix molecules on the chondrocytic phenotype, we have combined chondroitin sulfate-A (CSA) and chitosan, a glycosaminoglycan (GAG) analog, to develop a novel biomaterial to support chondrogenesis. Chitosan is a polycationic repeating monosaccharide of beta-1,4-linked glucosamine monomers with randomly located N-acetyl glucosamine units. Chitosan may be combined with the polyanionic CSA such that ionic crosslinking results in hydrogel formation. Bovine primary articular chondrocytes, when seeded onto a thin layer of CSA-chitosan, form discrete, focal adhesions to the material and maintain many characteristics of the differentiated chondrocytic phenotype, including round morphology, limited mitosis, collagen type II, and proteoglycan production. Our findings suggest CSA-chitosan may be well suited as a carrier material for the transplant of autologous chondrocytes or as a scaffold for the tissue engineering of cartilage-like tissue.     

The Pharmacokinetics of Recombinant Human Relaxin in Nonpregnant Women After Intravenous,Intravaginal, and Intracervical Administration

The pharmacokinetics of recombinant human relaxin (rhRlx) after intravenous (iv) bolus administration and the absorption of rhRlx after intracervical or intravaginal administration were determined in nonpregnant women. The study was conducted in two parts. In part I, 25 women received 0.01 mg/kg rhRlx iv. After a minimum 7-day washout period, these women were dosed intracervically (n = 10) or intravaginally (n = 15) with 0.75 or 1.5 mg rhRlx, respectively, in 3% methylcellulose gel. Part II was a double-blind, randomized, three-way crossover study in 26 women. At 1-month intervals, each woman received one of three intravaginal treatments consisting of 0 (placebo), 1, or 6 mg rhRlx in 3% methylcellulose gel. The serum concentrations of relaxin following iv administration were described as the sum of three exponentials. The mean (±SD) initial, intermediate, and terminal half-lives were 0.09 ± 0.04, 0.72 ± 0.11, and 4.6 ± 1.2 hr, respectively. Most of the area under the curve was associated with the intermediate half-life. The weight-normalized clearance was 170 ± 50 mL/hr/kg. The observed peak concentration was 98 ± 29 ng/mL, and the weight-normalized initial volume of distribution was 78 ± 40 mL/kg, which is approximately equivalent to the serum volume. If central compartment elimination was assumed, the volume of distribution at steady state (V _ss/W) was 280 ± 100 mL/kg, which is approximately equivalent to extracellular fluid volume. V _ss/W could be as large as 1300 ± 400 mL/kg without this assumption. After intravaginal administration of the placebo gel, endogenous relaxin concentrations were evident (i.e., 20 pg/mL) in 9 of the 26 women (maximum concentrations, 23–234 pg/mL). A similar proportion of women (approximately 35–40%) exhibited measurable serum concentrations of relaxin following intravaginal rhRlx treatment; this proportion increased to 90% following intracervical rhRlx treatment. For both routes of administration, the maximum serum concentrations of relaxin were usually within the range of values observed for endogenous relaxin, suggesting that the absorption of rhRlx was minimal.     

Otolaryngology Consultation for Peritonsillar Abscess in the Pediatric Population

Objective To assess clinical outcomes of children seen in consultation for peritonsillar abscess treated without the routine use of computed tomography or needle aspiration. Study Design Retrospective review of patients evaluated in the emergency department for possible peritonsillar abscess. Patient outcomes are reviewed with a statistical analysis of children grouped according to age. Methods A series of 102 patients, ages 8 months to 19 years, who were evaluated by the emergency department with otolaryngology consultation for possible peritonsillar abscess. All patients were admitted and given intravenous fluid replacement, antibiotics, and analgesia. Patients who responded to 24 hours of medical treatment were discharged, whereas patients who did not respond underwent elective tonsillectomy. Main Outcome Measure Outcome of patients evaluated for peritonsillar abscess treated without immediate surgery, needle aspiration, or computed tomography. Outcomes are correlated with age and clinical findings. Results Fifty‐two patients were discharged after initial medical therapy. Fifty patients underwent elective tonsillectomy; 40 of these patients were found to have abscesses at the time of surgery. When analyzed according to age, patients ages 8 months to 6 years were more likely to respond to medical treatment than children ages 7 to 12 and 12 to 19 (P = .023). Significant differences in the mean age of children requiring surgery (11.0 y) compared with those who responded to medical treatment (7.9 y) were observed (P = .003). Younger children who underwent tonsillectomy had a lower incidence of surgically confirmed abscess. Conclusions A significant number of children presenting with odynophagia, malaise, pharyngotonsillar bulge, and decreased oral intake respond to medical therapy without radiological evaluation or surgical intervention. Additionally, younger children (1–6 y) are more likely to respond to medical treatment than older children. Pertinent clinical data, as well as advantages and disadvantages of this approach, are discussed.     

Anaesthesia for Caesarean section in a patient with Watson’s syndrome

Watson’s syndrome is an uncommon genetic disorder whose features include mental retardation and pulmonary valvular stenosis. The purpose of this report is to describe one management strategy used successfully to anaesthetize a woman with this disorder who presented for Caesarean section. Epidural anaesthesia using 0.5% bupivacaine without epinephrine in 2–3 ml boluses to a total dose of 15 ml was administered over 30 min. Invasive haemodynamic monitoring in the form of arterial and central venous catheters were used to guide therapy and help ensure maternal and fetal well-being. Intravenous ketamine in doses of 10–20 mg every five minutes to a total dose of 245 mg (4.5 mg · kg^?1) was used to overcome the patient’s uncooperative nature and facilitate invasive procedures. Postoperative analgesia was provided using 3 mg epidural morphine. The patient was observed in the intensive care unit for the first postoperative day and experienced an uncomplicated intra- and postoperative course. We conclude that this technique represents a safe and effective method for anaesthetizing patients with this complicated problem for Caesarean section.