Injury patterns of e-scooter-related orthopaedic trauma in central London: a multicentre study.

PURPOSE: Electric scooters (e-Scooters) are being increasingly used in urban areas as a new means of transport. E-scooter sharing schemes have recently been piloted in the United Kingdom; however, there are no published data on orthopaedic injuries and user behaviour patterns in the UK. We aim to identify the patterns and severity of orthopaedic injuries related to e-scooter use. METHODS: We performed a retrospective review of all orthopaedic referrals relating to e-scooter use from 1 March to 30 November 2020 at three hospitals, including one major trauma centre in central London. Data including patient demographics, mechanism of injury, diagnosis and treatment were collected. RESULTS: One hundred and five orthopaedic injuries were identified in 83 patients. The median age was 32 years and 83% were male. Seventy-nine (95.2%) patients were riders, four were pedestrians. All e-scooters were privately owned. There were 93 fractures (88.6% of total injuries noted) including 12 (12.9%) open. Fifty-two (56.0%) were upper limb fractures, 39 (41.9%) lower limb and 2 (2.1%) spinal and rib fractures. Twenty-five patients (30.1%) required an operation and 29 (34.9%) required hospital admission. Helmet use was present in 34.1%. The most common place of injury was the road (65.1%) followed by pavement (32.9%). CONCLUSION: E-scooters can cause serious injury, most commonly in males. There was an equal distribution of upper and lower limb injuries, with many associated with high-energy trauma requiring operative intervention. Helmet use was seen in one third of riders. As e-scooter use continues to increase across the UK, additional steps should be taken to ensure the safety of the riders and public.

Assessment of liquid captopril formulations used in children.

OBJECTIVE: Unlicensed liquid captopril formulations are commonly used to treat children with heart disease. This study assessed the bioequivalence of two liquid preparations against a licensed tablet form. DESIGN: An open label, single dose, three-treatment, three-period, crossover trial. SETTING: Outpatient. PATIENTS: Healthy adult volunteers (n=18). INTERVENTIONS: Each subject was randomly assigned to one of six dosing sequences, and dosed with 25 mg captopril on each of three dosing visits separated by a washout of at least 14 days. Blood samples for pharmacokinetic analysis were taken at regular intervals (0 min to 10 h) post-dose. MAIN OUTCOME MEASURES: Bioequivalence of the formulations would be concluded if the 90% CI for the estimated ratio of the means of C(max) (maximum plasma concentrations) and area under curve(AUC) (extent of absorption) lay entirely within the range 0.8 to 1.25 RESULTS: Both liquid formulations failed the bioequivalence assessment with respect to C(max) and AUC. The 90% CI of the mean ratios of liquid/licensed tablet for both C(max) and AUC, fell outside the 0.8 to 1.25 limits. There was also considerable within-subject variability in C(max) (97.5%) and AUC (78.5%). CONCLUSIONS: Unlicensed captopril formulations are not bioequivalent to the licensed tablet form, or to each other, and so cannot be assumed to behave similarly in therapeutic use. Thus formulation substitution must be done with care and may require a period of increased monitoring of the patient. There is also significant within-subject variability in performance which has clinical implications with respect to titrating to an optimum therapeutic dose.

Covalent coupling of concanavalin A to a Carbopol 934P and 941P carrier in glucose-sensitive gels for delivery of insulin.

A novel glucose-sensitive gel formulation, containing concanavalin A and specific polysaccharides, was stabilised via covalent coupling to two structurally different carbomers. The bonding was done to minimise leaching of gel components thereby preventing toxicity and preserving the working mechanism of the gel. Increased gel stability was introduced by covalently bonding amine groups present on the lysine residues of concanavalin A to carboxylic moieties on Carbopol 934P NF and 941P NF using carbodiimide chemistry. The introduction of dextran then produced a glucose-sensitive formulation that transformed from gel to sol in the presence of free glucose. Rheological examination of glucose-sensitive gels stabilised in this way and containing varying concentrations of glucose was conducted with a cone and plate viscometer used in continual rotation mode. A decrease in viscosity over the chosen glucose concentration range was exhibited by both carbomer-stabilised formulations. The subsequent testing of such formulations in in-vitro diffusion experiments revealed that the leaching of concanavalin A from the covalently coupled gels is restricted significantly with respect to non-coupled formulations. In addition, insulin delivery in response to glucose in the physiologically relevant glucose concentration range has been demonstrated using the carbomer-stabilised gels at 37 degrees C. The performance of this self-regulating drug delivery system has been improved in terms of increased gel stability with reduced component leaching.

A covalently stabilised glucose responsive gel formulation with a Carbopol carrier.

A novel glucose-responsive gel formulation was stabilised via covalent coupling to a carbomer resin. The gel formed between the plant lectin, concanavalin A and specific polysaccharides was stabilised to minimise leaching of gel components into the surroundings. This was required to prevent toxicity and to preserve the working mechanism of the formulation. Increased gel stability was introduced by covalently bonding amine groups present on the lysine residues of concanavalin A to carboxylic moieties on Carbopol 974P NF using carbodiimide chemistry. The introduction of dextran then produced a glucose-responsive formulation that transformed from gel to sol in the presence of free glucose. The rheological properties and in vitro component and insulin release of the carbomer-stabilised gel were evaluated. A decrease in viscosity over a chosen glucose concentration range was exhibited by the carbomer-based gel. The testing of such a formulation in in vitro diffusion experiments revealed that the leaching of concanavalin A from the covalently coupled gels was restricted significantly with respect to a non-coupled gel. Insulin delivery in response to glucose in the physiologically relevant glucose concentration range was demonstrated using the carbomer-stabilised gel at 37 degrees C. The performance of this novel self-regulating drug delivery system has been improved in terms of increased gel stability with reduced component leaching.

Enoxaparin and bleeding complications: a review in patients with and without renal insufficiency.

STUDY OBJECTIVE: To compare the frequency of bleeding complications from enoxaparin in patients with normal renal function versus patients with renal insufficiency. DESIGN: Retrospective chart review. SETTING: University-based tertiary care center. PATIENTS: One hundred six patients who received two or more doses of enoxaparin. MEASUREMENTS AND MAIN RESULTS: Total bleeding complications occurred in 22% of patients with normal renal function and 51% with renal insufficiency (p<0.01). Major bleeds were also significantly different, 2% and 30%, respectively (p<0.001). No patients with normal renal function were given fresh-frozen plasma or packed red blood cells, whereas in those with renal insufficiency, 13% and 32%, respectively, received these products (p<0.01). CONCLUSION: Enoxaparin may have resulted in increased bleeding complications and use of blood products in patients with renal insufficiency. Prospective studies need to be conducted to define the drug's role and dosage adjustments in these patients.

Insulin delivery governed by covalently modified lectin-glycogen gels sensitive to glucose.

A glucose-sensitive gel formulation containing concanavalin A and glycogen has been reported previously. Precipitation resulting from the addition of concanavalin A to glycogen has been documented, but the formation of glucose-sensitive gels based on lectin-glycogen interactions is novel and used here in our studies. An improved in-vitro self-regulating drug-delivery system, using covalently modified glucose-sensitive gels based on concanavalin A and a polysaccharide displacement mechanism, is described. The successful use of the covalently modified gels addresses a problem identified previously where significant leaching of the mitogenic lectin from the gel membranes of non-coupled gels was encountered. Concanavalin A was covalently coupled to glycogen by use of derivatives of Schiff's bases. The resulting gels, like the non-coupled gels, were shown to undergo a gel-sol transformation in response to glucose. Insulin delivery was demonstrated using this covalently modified system in conditions of repeated glucose triggering at 20 degrees C and 37 degrees C. The magnitude of the response was less variable than for the dextran-based gels studied previously. The performance of this system has been improved in terms of concanavalin A leaching. This could, therefore, be used as the basis of the design of a self-regulating drug-delivery device for therapeutic agents used to treat diabetes mellitus.

Desensitization to allopurinol in a patient with previous failed desensitization.

OBJECTIVE: To describe an allopurinol desensitization that failed on the first attempt but was successful on the second attempt, resulting in the management of crippling tophaceous gout. CASE SUMMARY: A 64-year-old white man with a history of gouty nephropathy requiring hemodialysis developed a severe cutaneous reaction from exposure to allopurinol. The first desensitization attempt was unsuccessful, and the gouty nephropathy caused chronic cellulitus and urate microcrystal deposition on the patient's hands and feet. Continuous ambulatory peritoneal dialysis and hemodialysis were used to treat the patient's severe symptoms and increase uric acid clearance. This method, however, was ineffective. Severe tissue ischemia, requiring bilateral below-the-knee amputations, prompted the second desensitization attempt four years later. The second attempt, administered differently and with more caution, was successful and did not cause further complications. DISCUSSION: Allopurinol is the only agent available to effectively reduce uric acid concentrations in those who are over-producers. Hypersensitivity-type reactions have been reported with its use, and desensitization is the only viable therapeutic option. Few cases of desensitization to allopurinol have been reported in the literature. This article describes a failure and a subsequent success in desensitization to allopurinol. CONCLUSIONS: Although desensitization to allopurinol poses potential risks, the benefits can outweigh the risks of therapy. Desensitization requires close monitoring; if failure does occur, subsequent attempts can be successful, as this case report demonstrates.

The delivery of insulin from aqueous and non-aqueous reservoirs governed by a glucose sensitive gel membrane.

A self regulating delivery device, responsive to glucose, has been shown to operate successfully in vitro. This comprises a gel membrane which determines the delivery rate of insulin from a reservoir. The gel consists of a synthetic polysucrose and the lectin, concanavalin A. The mechanism is one of displacement of the branched polysaccharide from the lectin receptors by incoming glucose. The gel loses its high viscosity as a result but reforms on removal of glucose, thus providing the switch controlling the drug diffusion rate. The drug does not require to be chemically modified and thus the device is adaptable to other anti-hyperglycaemic drugs. However, results here indicate that the molecular weight of the solute may be an important parameter. Others include path length, gel formulation and temperature. It had been hypothesised that the reversal might be improved by the use of a non-aqueous reservoir of insulin. However, with the use of insulin, the switching off was found to be superior to that found with other test solutes used in previous studies, irrespective of the reservoir solvent. The advantages in the use of the non-aqueous system include, however, more reproducibility in the magnitude of response and a reduced temperature sensitivity.

Effect of arachidonic acid (ARA), prostaglandins E2 (PGE2), and F2alpha (PGF2alpha) on sensitized spleen cells in the hemolytic plaque assay.

Spleen cells from the BDF1 generation of DBA male X C57Bl/6 female matings sensitized with sheep erythrocytes (SRBC) were exposed to various concentrations of ARA, PGE2, and PGF2alpha for 90 minutes in vitro at 37 degrees C. Following exposure these sensitized spleen cells were then examined in the hemolytic plaque assay. No changes were demonstrated in the number of plaque forming cells (PFC) with 0.1 microgram/ml of ARA treatment. However, an increase in the number of PFC occurred with increasing concentrations of ARA. A significant increase (p less than 0.01) in PFC (59%) was shown with 10.0 microgram/ml of ARA. PGE2 treatment at 10.0 and 100.0 microgram/ml showed no evidence of increase, but a slight decrease (10%) was shown with 100.0 microgram/ml. On the other hand, exposure to PGF2alpha showed a significant increase (p less than 0.05) in PFC at the 10.0 microgram/ml (35%) and the 100.0 microgram/ml (29% levels, respectively. The data suggest that both ARA and PGF2alpha enhanced PFC formation.