Environmental impact of low-dose methoxyflurane versus nitrous oxide for analgesia: how green is the 'green whistle'?

BACKGROUND: The NHS has the target of reducing its carbon emission by 80% by 2032. Part of its strategy is using pharmaceuticals with a less harmful impact on the environment. Nitrous oxide is currently used widely within the NHS. Nitrous oxide, if released into the atmosphere, has a significant environmental impact. Methoxyflurane, delivered through the Penthrox 'green whistle' device, is a short-acting analgesic and is thought to have a smaller environmental impact compared with nitrous oxide. METHODS: Life cycle impact assessment (LCIA) of all products and processes involved in the manufacture and use of Penthrox, using data from the manufacturer, online sources and LCIA inventory Ecoinvent. These data were analysed in OpenLCA. Impact data were compared with existing data on nitrous oxide and morphine sulfate. RESULTS: This LCIA found that Penthrox has a climate change effect of 0.84 kg carbon dioxide equivalent (CO2e). Raw materials and the production process contributed to majority of the impact of Penthrox across all categories with raw materials accounting for 34.40% of the total climate change impact. Penthrox has a climate change impact of 117.7 times less CO2e compared with Entonox. 7 mg of 100 mg/100 mL of intravenous morphine sulfate had a climate change effect of 0.01 kg CO2e. CONCLUSIONS: This LCIA has shown that the overall 'cradle-to-grave' environmental impact of Penthrox device is better than nitrous oxide when looking specifically at climate change impact. The climate change impact for an equivalent dose of intravenous morphine was even lower. Switching to the use of inhaled methoxyflurane instead of using nitrous oxide in certain clinical situations could help the NHS to reach its carbon emission reduction target.

Innovations towards achieving environmentally sustainable operating theatres: A systematic review.

INTRODUCTION: The NHS accounts for 5.4% of the UK's total carbon footprint, with the perioperative environment being the most resource hungry aspect of the hospital. The aim of this systematic review was to assimilate the published studies concerning the sustainability of the perioperative environment, focussing on the impact of implemented interventions. METHODS: A systematic review was performed using Pubmed, OVID, Embase, Cochrane database of systematic reviews and Medline. Original manuscripts describing interventions aimed at improving operating theatre environmental sustainability were included. RESULTS: 675 abstracts were screened with 34 manuscripts included. Studies were divided into broad themes; recycling and waste management, waste reduction, reuse, reprocessing or life cycle analysis, energy and resource reduction and anaesthetic gases. This review summarises the interventions identified and their resulting effects on theatre sustainability. DISCUSSION: This systematic review has identified simple, yet highly effective interventions across a variety of themes that can lead to improved environmental sustainability of surgical operating theatres. Combining these interventions will likely result in a synergistic improvement to the environmental impact of surgery.

Expression of Endogenous Putative TSH Binding Protein in Orbit.

Thyroid stimulating antibodies (TSAB) cause Graves' disease and contribute to Graves' Orbitopathy (GO) pathogenesis. We hypothesise that the presence of TSH binding proteins (truncated TSHR variants (TSHRv)) and/or nonclassical ligands such as thyrostimulin (α2ß5) might provide a mechanism to protect against or exacerbate GO. We analysed primary human orbital preadipocyte-fibroblasts (OF) from GO patients and people free of GO (non-GO). Transcript (QPCR) and protein (western blot) expression levels of TSHRv were measured through an adipogenesis differentiation process. Cyclic-AMP production by TSHR activation was studied using luciferase-reporter and RIA assays. After differentiation, TSHRv levels in OF from GO were significantly higher than non-GO (p = 0.039), and confirmed in ex vivo analysis of orbital adipose samples. TSHRv western blot revealed a positive signal at 46 kDa in cell lysates and culture media (CM) from non-GO and GO-OF. Cyclic-AMP decreased from basal levels when OF were stimulated with TSH or Monoclonal TSAB (M22) before differentiation protocol, but increased in differentiated cells, and was inversely correlated with the TSHRv:TSHR ratio (Spearman correlation: TSH r = -0.55, p = 0.23, M22 r = 0.87, p = 0.03). In the bioassay, TSH/M22 induced luciferase-light was lower in CM from differentiated GO-OF than non-GO, suggesting that secreted TSHRv had neutralised their effects. α2 transcripts were present but reduced during adipogenesis (p < 0.005) with no difference observed between non-GO and GO. ß5 transcripts were at the limit of detection. Our work demonstrated that TSHRv transcripts are expressed as protein, are more abundant in GO than non-GO OF and have the capacity to regulate signalling via the TSHR.

The Role of Mitochondria-Linked Fatty-Acid Uptake-Driven Adipogenesis in Graves Orbitopathy.

CONTEXT: Depot-specific expansion of orbital adipose tissue (OAT) in Graves orbitopathy (GO; an autoimmune condition producing proptosis, visual impairment and reduced quality of life) is associated with fatty acid (FA)-uptake-driven adipogenesis in preadipocytes/fibroblasts (PFs). OBJECTIVE: This work sought a role for mitochondria in OAT adipogenesis in GO. METHODS: Confluent PFs from healthy OAT (OAT-H), OAT from GO (OAT-GO) and white adipose tissue in culture medium compared with culture medium containing a mixed hormonal cocktail as adipogenic medium (ADM), or culture-medium containing FA-supplementation, oleate:palmitate:linoleate (45:30:25%) with/without different concentration of mitochondrial biosubstrate adenosine 5'-diphosphate/guanosine 5'-diphosphate (ADP/GDP), AICAR (adenosine analogue), or inhibitor oligomycin-A for 17 days. Main outcome measures included oil-red-O staining and foci count of differentiated adipocytes for in vitro adipogenesis, flow cytometry, relative quantitative polymerase chain reaction, MTS-assay/106 cells, total cellular-ATP detection kit, and Seahorse-XFe96-Analyzer for mitochondria and oxidative-phosphorylation (OXPHOS)/glycolysis-ATP production analysis. RESULTS: During early adipogenesis before adipocyte formation (days 0, 4, and7), we observed OAT-specific cellular ATP production via mitochondrial OXPHOS in PFs both from OAT-H and OAT-GO, and substantially disrupted OXPHOS-ATP/glycolysis-ATP production in PFs from OAT-GO, for example, a 40% reduction in OXPHOS-ATP and trend-increased glycolysis-ATP production on days 4 and 7 compared with day 0, which contrasted with the stable levels in OAT-H. FA supplementation in culture-medium triggered adipogenesis in PFs both from OAT-H and OAT-GO, which was substantially enhanced by 1-mM GDP reaching 7% to 18% of ADM adipogenesis. The FA-uptake-driven adipogenesis was diminished by oligomycin-A but unaffected by treatment with ADP or AICAR. Furthermore, we observed a significant positive correlation between FA-uptake-driven adipogenesis by GDP and the ratios of OXPHOS-ATP/glycolysis-ATP through adipogenesis of PFs from OAT-GO. CONCLUSION: Our study confirmed that FA uptake can drive OAT adipogenesis and revealed a fundamental role for mitochondria-OXPHOS in GO development, which provides potential for therapeutic interventions.

Ophthalmic emergencies presenting to the emergency department at the University Hospital of Wales, Cardiff, UK.

BACKGROUND: Community-based optometry services are increasingly used as a primary resource for patients with acute eye problems. The Eye Health Examination Wales (EHEW) is an example of one such established scheme. The aim of the project was to show how the aforementioned pathway has affected the presentation of ocular conditions to a general emergency department and the eye casualty department at the same hospital. METHODS: Clinical data were collected prospectively over a one-month period. The records of 100 consecutive patients with ocular pathology presenting to a general emergency department were analysed. Numbers were also obtained for the number of patients seen under the EHEW scheme by community optometrists for the same period. The notes of patients referred to ophthalmology or back out to the community optometry scheme were followed to monitor for re-attendance in either setting. RESULTS: Eighty-five per cent of patients were walk-in cases. The most common diagnosis made in the emergency department was 'no abnormality found' in 37 per cent. Eighty per cent of all conditions were discharged from the emergency department. Fifteen per cent of all cases, mainly foreign body-related, were followed up in the emergency eye clinic and 10 per cent were sent to EHEW for follow-up. No cases re-presented to a hospital service at a later date. CONCLUSION: At least 37 per cent of emergency department cases could have been potentially avoided had the patient presented to the EHEW scheme. The pathway for patients to be sent from the emergency department to an EHEW optometrist does not appear to delay presentation to an ophthalmologist thereafter. Further promotion of the EHEW service is needed to change patient behaviours and reduce avoidable attendance to overstretched emergency departments.

Prostaglandin F2-Alpha Eye Drops (Bimatoprost) in Graves' Orbitopathy: A Randomized Controlled Double-Masked Crossover Trial (BIMA Trial).

BACKGROUND: Previous in vitro experiments have demonstrated that prostaglandin F2-alpha (PF2α) reduced proliferation and adipogenesis in a murine cell line and human orbital fibroblasts derived from subjects with inactive Graves' orbitopathy (GO). The objective of this study was to determine if the PGF2α analogue bimatoprost is effective at reducing proptosis in this population. METHODS: A randomized controlled double-masked crossover trial was conducted in a single tertiary care academic medical center. Patients with long-standing, inactive GO but persistent proptosis (>20 mm in at least one eye) were recruited. Allowing for a 15% dropout rate, 31 patients (26 females) were randomized in order to identify a treatment effect of 2.0 mm (p = 0.05; power 0.88). Following informed consent, participants were randomized to receive bimatoprost or placebo for three months, after which they underwent a two-month washout before switching to the opposite treatment. The primary outcome was the change in exophthalmometry readings over the two three-month treatment periods. RESULTS: The mean exophthalmometer at baseline was 23.6 mm (range 20.0-30.5 mm), and the mean age of the patients was 55 years (range 28-74 years). The median duration of GO was 7.6 years (interquartile range 3.6-12.3 years). The majority were still suffering from diplopia (61.3%) with bilateral involvement (61.3%). Using multi-level modeling adjusted for baseline, period, and carry-over, bimatoprost resulted in a -0.17 mm (reduction) exophthalmometry change ([confidence interval -0.67 to +0.32]; p = 0.490). There was a mean change in intraocular pressure of -2.7 mmHg ([confidence interval -4.0 to -1.4]; p = 0.0070). One patient showed periorbital fat atrophy on treatment, which resolved on stopping treatment. Independent analysis of proptosis by photographic images (all subjects) and subgroup analysis on monocular disease (n = 12) did not show any apparent benefit. CONCLUSIONS: In inactive GO, bimatoprost treatment over a three-month period does not result in an improvement in proptosis.

Management of acute retrobulbar haemorrhage: a survey of non-ophthalmic emergency department physicians.

INTRODUCTION: Acute retrobulbar haemorrhage (RBH) with orbital compartment syndrome is a sight-threatening ophthalmic emergency requiring treatment with lateral canthotomy and cantholysis (LC/C). However, such cases may present to non-ophthalmic emergency departments (ED) out-of-hours, when specialist intervention is not readily available. We completed a survey of ED physicians to explore experiences of RBH and confidence in undertaking LC/C. METHODS: From February to April 2018, an online survey was sent to ED physicians of all training grades in seven UK locations. The survey comprised a case vignette of a patient presenting with clinical features of RBH with orbital compartment syndrome, with multiple choice questions on the diagnosis, management and onward referral of such cases. Additional questions explored the experience of RBH, LC/C and perspectives on current and future training of ED physicians in this area. RESULTS: 190 ED doctors completed the survey (response rate 70%). While 82.8% correctly diagnosed RBH and 95.7% recognised irreversible visual loss as a consequence of untreated RBH with orbital compartment syndrome, 78.7% indicated that they would initially undertake CT imaging rather than performing LC/C. Only 38.9% had previously encountered a case of RBH and only 37.1% would perform LC/C themselves, with 91.4% indicating that this was due to lack of training. 92.2% felt that more training was required for ED physicians in RBH management and performing LC/C. CONCLUSION: While cases of RBH with orbital compartment syndrome are infrequent, it is important that RBH management with the vital, sight-saving skill of LC/C is added to the United Kingdom Royal College of Emergency Medicine training curriculum. At present, though the majority of ED physicians can identify RBH, the minority are willing or able to undertake LC/C, potentially risking irreversible but avoidable visual loss.

Pulmonary embolism, frostbite and high-altitude retinopathy - a combination of life- and sight-threatening vascular complications at high altitude.

The effects of high altitude on the human vascular system are well described. This case demonstrates an interesting combination of vascular complications at high altitude which were both life- and sight-threatening. In May 2017, during an attempt on Mount Everest, a 58-year-old man was forced to descend from 8000 m because of adverse weather. He suffered significant frostbite of his right hand, later requiring termination of the distal phalanx of one of the affected digits. He also experienced increasing breathlessness and went on to develop pleuritic chest pain. A CT pulmonary angiogram performed upon return to sea level revealed multiple small sub-segmental pulmonary emboli. He was anticoagulated for three months and made a full recovery. The patient also reported visual loss in the left eye and on ophthalmic examination was found to have multiple retinal haemorrhages including a left macular haemorrhage, consistent with high altitude retinopathy. The retinal haemorrhages settled with conservative management. The vascular complications suffered by this patient demonstrate the potentially fatal changes that can occur at altitude. They also serve to act as a reminder for physicians, even at sea level of the potential complications in patients returning from high altitude.

A case of mistaken identity: the role of lacrimal gland pleomorphic adenoma tissue diagnosis.

PURPOSE: Lacrimal gland lesions have diverse pathologies. Bone remodelling on imaging may suggest a benign lacrimal gland pleomorphic adenoma (LGPA) rather than a malignant process. METHODS: The authors report a case of malignant pleomorphic adenocarcinoma, which was misdiagnosed clinico-radiologically as a benign LGPA. Lesions with bone remodelling on CT imaging were subsequently analysed amongst a cohort of 31 lacrimal gland lesions from a single tertiary centre. RESULTS: 31 lacrimal gland lesions biopsied over a ten-year period featured bone remodeling on CT scan, typical of LGPA. Three diagnoses were of pleomorphic adenocarcinoma. Two of these cases presented classically with unilateral painful eyelid swelling and bone destruction or bone erosion on CT scan. Seven patients (23%) in this ten-year period had bone remodeling on CT scan, typical of LGPA. Of these seven cases, three were LGPA, but the other four cases were a mixture of other diagnoses. CONCLUSION: Clinical and radiological suspicion of LGPA may be inaccurate and requires prompt histological diagnosis to facilitate appropriate further treatment and prognosis.

Evolution of design considerations in complex craniofacial reconstruction using patient-specific implants.

Previously published evidence has established major clinical benefits from using computer-aided design, computer-aided manufacturing, and additive manufacturing to produce patient-specific devices. These include cutting guides, drilling guides, positioning guides, and implants. However, custom devices produced using these methods are still not in routine use, particularly by the UK National Health Service. Oft-cited reasons for this slow uptake include the following: a higher up-front cost than conventionally fabricated devices, material-choice uncertainty, and a lack of long-term follow-up due to their relatively recent introduction. This article identifies a further gap in current knowledge - that of design rules, or key specification considerations for complex computer-aided design/computer-aided manufacturing/additive manufacturing devices. This research begins to address the gap by combining a detailed review of the literature with first-hand experience of interdisciplinary collaboration on five craniofacial patient case studies. In each patient case, bony lesions in the orbito-temporal region were segmented, excised, and reconstructed in the virtual environment. Three cases translated these digital plans into theatre via polymer surgical guides. Four cases utilised additive manufacturing to fabricate titanium implants. One implant was machined from polyether ether ketone. From the literature, articles with relevant abstracts were analysed to extract design considerations. In all, 19 frequently recurring design considerations were extracted from previous publications. Nine new design considerations were extracted from the case studies - on the basis of subjective clinical evaluation. These were synthesised to produce a design considerations framework to assist clinicians with prescribing and design engineers with modelling. Promising avenues for further research are proposed.

Inverted Papilloma Originating Primarily from the Nasolacrimal Duct: A Case Report and Review of the Pertinent Literature.

Introduction. Inverted papilloma (IP) is an uncommon, benign yet aggressive neoplasm characterised by high recurrence rates and tendency towards malignant transformation. The majority of IP cases originate in the ethmoid region, lateral wall of the nasal fossa, and maxillary sinus. The authors report a case of an IP originating primarily from the nasolacrimal duct (NLD). Case. A 69-year-old Caucasian gentleman presented with a lump in his right medial canthal region, epiphora, and discharge bilaterally. Radiological investigation revealed a well-defined, heterogeneous mass within the proximal NLD eroding the bony canal, protruding into the middle meatus and into the right orbit. The tumour was excised en bloc utilizing a combined external and endoscopic approach based on its location. Histology revealed hyperplastic ribbons of basement membrane-enclosed epithelium growing endophytically into the underlying stroma with no evidence of invasive malignancy. The patient made an uneventful recovery with unchanged visual acuity and normal extraocular movements. Conclusion. The case demonstrates variability within the sinonasal tract that IP can develop and the individuality of each case necessitating tailored operative techniques for complete excision whilst minimising recurrence rates. We also present a combined endoscopic approach for the en bloc resection of a NLD IP with no clinical recurrence at 15-month follow-up.

State-Issued Identification Cards Reveal Patterns in Adult Weight Status.

BACKGROUND: State-issued identification cards are a promising data source for neighborhood-level obesity estimates. METHODS: We used information from three million Oregon state-issued identification cards to compute age-adjusted estimates of average adult body mass index (BMI) for each census tract in the state. We used multivariate linear regression to identify associations between weight status and population characteristics, food access, commuting behavior, and geography. RESULTS: Together, home values, education, race, ethnicity, car commuting, and rural-urban commuting area (RUCA) explained 86% of the variation in BMI among tracts. BMI was lower in areas with higher home values and greater educational attainment, and higher in areas with more workers commuting by car. DISCUSSION: Our findings are consistent with other research on socioeconomic disparities in obesity. This demonstrates state-issued identification cards are a promising data source for BMI surveillance and may offer new insight into the association between weight status and economic and environmental factors. Public health agencies should explore options for developing their own obesity estimates from identification card data.

A survey of UK practice patterns in the delivery of intravitreal injections.

PURPOSE: To assess UK practice patterns related to the prescription of antibiotics before, during and after intravitreal injections, the location where injections are carried out and the qualifications of those administering the injections. METHODS: Every ophthalmology unit featured in the Royal College of Ophthalmologists (UK) training directory was contacted. A healthcare professional involved in giving intravitreal injections at each institution completed a questionnaire regarding local practice patterns. RESULTS: A response rate of 85% (115/136) was achieved. Seventy four percent of hospitals (85/115) gave take home antibiotics post intravitreal injection. Twenty three percent (26/115) of hospitals employed non-medical healthcare professionals to administer injections and 83% (96/115) administered intravitreal injections in a dedicated clean room as opposed to an operating theatre. CONCLUSION: Practice patterns for intravitreal injection vary considerably. Guidelines alone do not appear to be effective in reducing practices which are considered wasteful and other approaches need to be developed.

Using state-issued identification cards for obesity tracking.

Obesity prevention has emerged as one of public health's top priorities. Public health agencies need reliable data on population health status to guide prevention efforts. Existing survey data sources provide county-level estimates; obtaining sub-county estimates from survey data can be prohibitively expensive. State-issued identification cards are an alternate data source for community-level obesity estimates. We computed body mass index for 3.2 million adult Oregonians who were issued a driver license or identification card between 2003 and 2010. Statewide estimates of obesity prevalence and average body mass index were compared to the Oregon Behavioral Risk Factor Surveillance System (BRFSS). After geocoding addresses we calculated average adult body mass index for every census tract and block group in the state. Sub-county estimates reveal striking patterns in the population's weight status. Annual obesity prevalence estimates from identification cards averaged 18% lower than the BRFSS for men and 31% lower for women. Body mass index estimates averaged 2% lower than the BRFSS for men and 5% lower for women. Identification card records are a promising data source to augment tracking of obesity. People do tend to misrepresent their weight, but the consistent bias does not obscure patterns and trends. Large numbers of records allow for stable estimates for small geographic areas.

Eye problems on expeditions.

BACKGROUND: Visual loss in the wilderness setting is at best disabling and at worst potentially fatal. However many physicians have a poor knowledge of ophthalmology and the basic skills that could be applied in situations away from definitive care. METHOD: This paper is intended for physicians, interested non-medical people and expedition operators as a practical guide to the treatment and prevention of eye problems on expeditions. RESULTS: Some of the eye conditions described in this paper are unique to the high altitude setting, such as high altitude retinopathy and some could happen in any environment, such as trauma, dry eyes and contact lens problems. As with any aspect of an expedition, preparation is vital to prevent and avoid eye problems. It is therefore important that pre-existing ocular conditions are known about and appropriate drugs and equipment are available in expedition first aid kits. CONCLUSIONS: In the event of a visual problem, it is always better to be cautious and evacuate a patient rather than a risk a sight-threatening complication. However this paper should provide a non-ophthalmologist with the skills to treat the eye conditions described.