Pediatric electric scooter injuries in the UK: Case series and review of literature.

OBJECTIVE: Electric scooters are being used worldwide as a new means of transport and e-scooter shared schemes are currently being piloted in cities across the UK. At present, there is no data published looking at pediatric e-scooter injuries within the UK. We aim to assess if e-scooters pose a risk to children and the patterns and severity of orthopedic injuries related to their use. METHODS: We performed a retrospective review of all orthopedic pediatric referrals relating to e-scooter use from January 1 to December 31, 2020 at two hospitals, including one pediatric Major Trauma Center in central London. Data including patient demographics, mechanism of injury, diagnosis, and treatment were collected. RESULTS: Ten patients were identified in this series, of which 5 required orthopedic surgery. Four patients required admission to hospital from the emergency department. The median age was 15 (range 13-17 years) and all were male. All e-scooters were privately owned and all sustained a fall whilst riding the e-scooter. No patient was wearing a helmet. Six sustained lower limb injuries and four upper limb injuries. Two patients were trauma called and one patient sustained an open fracture. There were no mortalities at 30 days. CONCLUSION: E-scooters pose a significant risk to children and can be associated with severe musculoskeletal injury. The risk they pose to the pediatric population should not be overlooked and these findings may inform public policy regarding the restriction of electric scooter use in children.

Predicting Regulatory Product Approvals Using a Proposed Quantitative Version of FDA's Benefit-Risk Framework to Calculate Net-Benefit Score and Benefit-Risk Ratio.

BACKGROUND: Approval of regulated medical products in the USA is based upon a rigorous review of the benefits and risks as performed by the US Food and Drug Administration (FDA) staff of scientists and is summarized in a descriptive and qualitative format called the FDA's Benefit-Risk Framework (BRF). This present method highlights the key factors in regulatory decision-making, but does not clearly define the reason for its final approval. METHOD: This study proposes a quantitative version of FDA's BRF to calculate a Net-Benefit Score and a Benefit-Risk Ratio as a method to define a single-value summary of the tradeoffs between benefits and risks and allow comparisons among other products. In this retrospective review of five years of new molecular entities and new biologic (N = 185 products) regulatory decision-making, this proposed scoring system codifies and quantitates the information about a product's benefits, risks, and risk management information in a format that may predict why regulated medical products are approved in the USA. RESULTS: Simple calculation of codified benefits, risks, and risk mitigations with numerical limits is proposed to provide a repeatable process and transparency for documenting the net-benefit of regulatory product approval. CONCLUSION: Use of a strict process of collecting, codifying, and analyzing public information to determine a Net-Benefit score and a Benefit-Risk Ratio is possible to anticipate regulatory product approval.

The impact of the novel coronavirus on trauma and orthopaedics in the UK.

At first glance, the novel coronavirus pandemic and orthopaedic surgery appear separate entities. Orthopaedic surgeons are not generally considered front-line staff in terms of the treatment of the disease that the novel coronavirus causes compared with anaesthetic and medical colleagues. However, the impact that the novel coronavirus is likely to have on the musculoskeletal injury burden and the morbidity associated with chronic musculoskeletal disease is significant. This article summarises the strategies currently being developed for the remodelling of orthopaedic services in the UK and the emergency British Orthopaedic Association Standards for Trauma and Orthopaedic guidelines released on 24 March 2020 in managing urgent orthopaedic patients during the novel coronavirus pandemic.

The Science of Developing Appealing Flavors to Drive Compliance.

OBJECTIVES: To develop flavors for oral care formulations containing zinc oxide, zinc citrate and L-arginine that are stable for the toothpaste shelf life, mask the unpleasant astringency and metallic off notes of the base, have an appealing taste which pleases global consumers, stimulate regimen compliance, and therefore help deliver whole mouth health benefits to people throughout the world. METHODS: For stability evaluation, flavor materials were formulated in Dual Zinc plus Arginine base and these samples were subjected to accelerated aging which consists of exposure to a temperature of 49°C for 6 weeks. The samples were analyzed by gas chromatography with flame ionization detector (GC FID) and gas chromatography mass spectrometry (GC MS) to confirm stability or establish changes in the chemical profile - loss of material and generation of degradation compounds. These samples were evaluated organoleptically by a flavor expert for taste acceptability and changes due to instability. Using state-of-the-art flavor expertise, tailor-made flavors were created. Their consumer appeal and acceptance were validated with monadic identified product tests. Their cooling attributes were evaluated by a panel of creative flavorists. RESULTS: Certain classes of flavor molecules were not stable in the zinc and arginine-containing dentifrice. This significantly limited the choice of flavor materials that could be used to mitigate the undesirable taste of the dentifrice excipients and provide consumer acceptable taste. Through understanding of consumer expectations and needs, creative formulation using stable raw materials, and various novel cooling technologies, we were able to prepare flavors that successfully masked the unpleasant mouth sensation of the zinc and arginine-containing base. These specially designed flavors also provided impactful long-lasting cooling and freshness, thus complementing the toothpaste's therapeutic benefits. Consumer tests validated that these flavors had strong performance and acceptability among users of the original Colgate® Total® triclosan-containing dentifrice. CONCLUSIONS: Combining in-depth flavor scientific research and formulation creativity, we were able to deliver flavors that are stable and appealing to the global consumer for Colgate's new therapeutic segment.

A novel freehand method for patellar resurfacing in total knee replacement.

Patellar resurfacing in the context of primary total knee replacement (TKR) and in the presence of patella-femoral osteoarthritis is common and widespread practice, as it reduces the rate of re-operation and anterior knee pain. There are several measuring devices and cutting jigs available in the market, which aim to aid with accurately resecting the patellar articular surface. A common characteristic of these jigs is that the patella needs to be everted at some stage to apply them and use them. The senior author of this paper has developed a method of performing patellar resection with the use of simple instruments with no need to evert it and while it engages the trochlea in a physiological position. We propose that this method is reproducible and produces cuts that are parallel to the trochlea.

Van Nes rotationplasty as a treatment method for Ewing's sarcoma in a 14-month-old.

INTRODUCTION: In recent years, the rotationplasty procedure has become popular amongst tumour surgeons as an alternative to endoprosthetic replacement or amputation. There are very few documented cases of this technique in young patients with malignancy. PRESENTATION OF CASE: We describe an extremely rare case of Ewing's sarcoma in a 14-month-old boy that involved the entire length of the left femur. At initial presentation, pulmonary metastatic spread had occurred and there was no neurovascular involvement. Complete response to neo-adjuvant chemotherapy was achieved prior to performing the definitive surgical procedure. DISCUSSION: This case highlights the many reconstructive options and difficulties encountered in managing such extremely young patients with aggressive malignant disease. In this case, a complete femoral excision was necessary and various treatment options were explored. These included irradiation and re-implantation, endoprosthetic replacement and manufacturing a custom growing prosthesis. Taking future functional, psychological and social implications into consideration, we performed a total femoral excision and Van Nes rotationplasty of the tibia at our institute. Histological analysis of the tumour resection showed clear tumour margins and at 1 year clinical review, the patient demonstrates good functional outcome with no evidence of disease recurrence. CONCLUSION: Van Nes rotationplasty is a viable reconstructive option in young patients with sarcoma of the femur. We believe this to be the youngest reported case of rotationplasty in current literature.

Implant use for primary hip and knee arthroplasty: are we getting it right first time?

Implants used for hip and knee arthroplasties have recently come under increased scrutiny. In England, a large variety of prostheses are currently being used. With the need for savings within the NHS of up to £20 billion over the next five years, we should be 'getting it right first time' by using the most reliable implants with proven survivorship. The 8th Annual Report from the NJR (2011) reporting on prostheses used in 2010 was analysed to determine whether implants had published survivorship data. This study demonstrates that the majority of implants did have long-term results but a small percentage had no published data. The cost of these implants was calculated to see if the implants provided best value for money based on survivorship. Implant choice was also correlated to revision rates published in the NJR report (2011) to help determine whether their continued use was justified.

Displacement of a cemented femoral implant. A complication of manipulation of a dislocated total hip replacement.

Dislocation is a common complication of total hip replacement, which has been quoted in the literature as having an incidence of 1-4%. This is commonly treated with closed reduction. The authors present a case report of displacement of a cemented smooth-polished tapered femoral stem, which occurred while attempting closed reduction of a dislocated hybrid total hip replacement. The patient required full revision arthroplasty.

Absence of integrin αvß3 enhances vascular leak in mice by inhibiting endothelial cortical actin formation.

RATIONALE: Sepsis and acute lung injury (ALI) have devastatingly high mortality rates. Both are associated with increased vascular leak, a process regulated by complex molecular mechanisms. OBJECTIVES: We hypothesized that integrin αvß3 could be an important determinant of vascular leak and endothelial permeability in sepsis and ALI. METHODS: ß3 subunit knockout mice were tested for lung vascular leak after endotracheal LPS, and systemic vascular leak and mortality after intraperitoneal LPS and cecal ligation and puncture. Possible contributory effects of ß3 deficiency in platelets and other hematopoietic cells were excluded by bone marrow reconstitution experiments. Endothelial cells treated with αvß3 antibodies were evaluated for sphingosine-1 phosphate (S1P)­mediated alterations in barrier function, cytoskeletal arrangement, and integrin localization. MEASUREMENTS AND MAIN RESULTS: ß3 knockout mice had increased vascular leak and pulmonary edema formation after endotracheal LPS, and increased vascular leak and mortality after intraperitoneal LPS and cecal ligation and puncture. In endothelial cells, αvß3 antibodies inhibited barrier-enhancing and cortical actin responses to S1P. Furthermore, S1P induced translocation of αvß3 from discrete focal adhesions to cortically distributed sites through Gi- and Rac1-mediated pathways. Cortical αvß3 localization after S1P was decreased by αvß3 antibodies, suggesting that ligation of the αvß3 with its extracellular matrix ligands is required to stabilize cortical αvß3 focal adhesions. CONCLUSIONS: Our studies identify a novel mechanism by which αvß3 mitigates increased vascular leak, a pathophysiologic function central to sepsis and ALI. These studies suggest that drugs designed to block αvß3 may have the unexpected side effect of intensifying sepsis- and ALI-associated vascular endothelial leak.

ALO-01 (morphine sulfate and naltrexone hydrochloride) extended-release capsules in the treatment of chronic pain of osteoarthritis of the hip or knee: pharmacokinetics, efficacy, and safety.

UNLABELLED: ALO-01 (EMBEDA [morphine sulfate and naltrexone hydrochloride] extended-release capsules [King Pharmaceuticals, Inc, Bridgewater, NJ]), indicated for chronic moderate-to-severe pain, is designed to release naltrexone upon tampering (eg, by crushing), reducing morphine-induced subjective effects. This multicenter, randomized, double-blind, crossover study assessed pharmacokinetics, efficacy, and safety of ALO-01 and compared them with extended-release morphine sulfate (ERMS, KADIAN [morphine sulfate extended-release] capsules [Actavis US, Morristown, NJ]) in adults (N = 113) with osteoarthritis pain. Study periods included washout until pain flare (intensity > or =5, 0 to 10; 0 = no pain, 10 = worst pain); dose titration with ERMS (20 to 160mg BID); and randomization to 2 (crossover) 14-day treatment periods with ERMS or ALO-01, separated by 7 days of open-label ERMS. Assessments included pharmacokinetics (morphine, naltrexone), pain scores (0 to 10), Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index; Patient Global Assessment of Medication (1 to 5; poor to excellent). Mean score at pain flare was 7.1. Morphine exposure from both formulations at steady state was similar. Plasma naltrexone concentrations were below limit-of-quantification for most patients and, when present, did not impact pain scores. During treatment, mean pain intensity (day 14: ERMS, 2.4; ALO-01, 2.3, P = .31), WOMAC change-from-baseline (mean pain, physical function, composite scores), and adverse event frequency were similar. ALO-01 and ERMS provided similar relief of osteoarthritis pain. PERSPECTIVE: We present data demonstrating that ALO-01 has steady-state morphine exposure, efficacy, and safety similar to marketed ERMS capsules. Results highlight the potential for morphine in ALO-01 to manage moderate-to-severe osteoarthritis pain, while the sequestered naltrexone does not interfere with efficacy.

Effect of concomitant ingestion of alcohol on the in vivo pharmacokinetics of KADIAN (morphine sulfate extended-release) capsules.

UNLABELLED: The recent withdrawal of hydromorphone hydrochloride extended-release capsules (Palladone; Purdue Pharma L.P., Stamford, CT) from the market after pharmacokinetic data revealed a risk of alcohol-induced dose-dumping prompted a re-examination of the risk-benefit profiles of extended-release drugs. Although warnings on concomitant alcohol use are included on opioid product labels, further investigations of extended-release formulations to determine the risk of dose-dumping were recommended by the US Food and Drug Administration. The present study was undertaken to assess the single-dose relative bioavailability of polymer-coated, extended-release morphine sulfate capsules (KADIAN, 100 mg; Alpharma Pharmaceuticals LLC, Piscataway, NJ). This open-label, randomized, 3-way crossover study with an additional index arm, conducted among 32 healthy male volunteers, found no significant evidence of a formulation interaction between KADIAN and alcohol, in vivo. The pharmacokinetics of serum morphine did not differ significantly among subjects taking KADIAN with water (fasted) or with 240 mL 40% alcohol under fasted or fed conditions. Analysis of variance ratios of least-squares means for ln-transformed AUC(infinity) and C(max) satisfied the criteria (90% confidence intervals within 80%-125%) to declare no drug formulation interaction among the KADIAN regimens dosed with alcohol compared with KADIAN taken with water. There were no serious adverse events or deaths reported during the study. PERSPECTIVE: Because of the high rate of alcohol use in the United States, the potential for drug-alcohol interactions is an important clinical concern. Although it is recommended that alcohol not be used while the patient is taking opioids, results of this in vivo study indicate that the risk of alcohol-induced dose-dumping in connection with the use of KADIAN is negligible.