Managing magnets: An audit of introduction of the Royal College of Emergency Medicine Best Practice Guideline.

AIM: To evaluate management of children and young people presenting to the Emergency Department (ED) with magnet ingestion before and after new guidance. METHODS: In May 2021, a National Patient Safety Agency and Royal College of Emergency Medicine (RCEM) Best Practice Guideline about management of ingested magnets was published. This was implemented in our department. Children and young people presenting after magnet ingestion were identified from SNOMED (coded routinely collected data) and X-ray requests between January 2016 and March 2022. Management was compared to national guidance. RESULTS: There were 138 patient episodes of magnet ingestion, with a rising incidence over the 5-year period. Following introduction of the guideline, there was a higher incidence of admission (36% vs. 20%) and operative intervention (15.7% vs. 8%). Use of follow-up X-ray increased from 56% to 90%. There was substantial variation in the management prior to guidance which reduced after introduction of the RCEM guidance. CONCLUSION: Management of magnet ingestion has become more standardised since introduction of the National RCEM Best Practice Guideline, but there is still room for improvement.

Randomized efficacy and safety trial of once-daily remogliflozin etabonate for the treatment of type 2 diabetes.

The sodium-dependent glucose transporter 2 (SGLT2) inhibitor remogliflozin etabonate (RE) was evaluated in a 12-week, double-blind, randomized, placebo- and active-controlled, parallel-group study. A total of 252 newly diagnosed and drug-naïve people with type 2 diabetes and glycated haemoglobin (HbA1c) concentrations of 7.0-≤9.5% (53-80 mmol/mol) were recruited. Participants were randomized to RE (100, 250, 500 or 1000 mg once daily or 250 mg twice daily), placebo or 30 mg pioglitazone once daily. The primary endpoint was change in HbA1c concentration from baseline. Secondary endpoints included changes in fasting plasma glucose, body weight and lipid profiles, safety and tolerability. We observed a statistically significant trend in the RE dose-response relationship for change from baseline in HbA1c at week 12 (p < 0.047). RE was generally well tolerated and no effects on LDL cholesterol were observed.

Short bowel syndrome: a practical pathway leading to successful enteral autonomy.

BACKGROUND: Short bowel syndrome is a multisystemic disorder that results from the loss of a significant amount of small bowel. The goal of treatment in these patients is to achieve complete enteral autonomy while minimizing complications. Our unit has 30 years of experience in the management of short gut patients. During the past decade, our results have improved significantly, especially in children with severe short bowel syndrome. This brief communication looks at the algorithm presently used in our unit. METHODS: In this communication, the principles in management of short bowel syndrome in our unit are discussed. In addition, our algorithm is published for the first time. A brief summary of our results is provided. RESULTS: Twenty-seven children were enrolled from 2000 to 2009. In this cohort, two patients died because of significant liver disease: one after having two liver and bowel transplants. Overall, survival stands at 92%. All had autologous gastrointestinal reconstruction, and 19 patients underwent bowel lengthening (longitudinal intestinal lengthening and tailoring). The median residual length of bowel of this subgroup at first operation was 25 cm in those who had their gut measured. Two patients were lost to follow-up. Two patients remain on supplemental total parenteral nutrition (TPN), with an overall 91% of surviving patients off TPN at a median of 6 months after reconstruction. CONCLUSIONS: We believe this improvement is related to the development-over many years-of a structured pathway for managing these patients.

Assessing the fugitive emission of CH4 via migration along fault zones - Comparing potential shale gas basins to non-shale basins in the UK.

This study considered whether faults bounding hydrocarbon-bearing basins could be conduits for methane release to the atmosphere. Five basin bounding faults in the UK were considered: two which bounded potential shale gas basins; two faults that bounded coal basins; and one that bounded a basin with no known hydrocarbon deposits. In each basin, two mobile methane surveys were conducted, one along the surface expression of the basin bounding fault and one along a line of similar length but not intersecting the fault. All survey data was corrected for wind direction, the ambient CH4 concentration and the distance to the possible source. The survey design allowed for Analysis of Variance and this showed that there was a significant difference between the fault and control survey lines though a significant flux from the fault was not found in all basins and there was no apparent link to the presence, or absence, of hydrocarbons. As such, shale basins did not have a significantly different CH4 flux to non-shale hydrocarbon basins and non-hydrocarbon basins. These results could have implications for CH4 emissions from faults both in the UK and globally. Including all the corrected fault data, we estimate faults have an emissions factor of 11.5±6.3tCH4/km/yr, while the most conservative estimate of the flux from faults is 0.7±0.3tCH4/km/yr. The use of isotopes meant that at least one site of thermogenic flux from a fault could be identified. However, the total length of faults that penetrate through-basins and go from the surface to hydrocarbon reservoirs at depth in the UK is not known; as such, the emissions factor could not be multiplied by an activity level to estimate a total UK CH4 flux.

Fugitive emissions of methane from abandoned, decommissioned oil and gas wells.

This study considered the fugitive emissions of methane (CH4) from former oil and gas exploration and production wells drilled to exploit conventional hydrocarbon reservoirs onshore in the UK. This study selected from the 66% of all onshore wells in the UK which appeared to be properly decommissioned (abandoned) that came from 4 different basins and were between 8 and 79 years old. The soil gas above each well was analysed and assessed relative to a nearby control site of similar land use and soil type. The results showed that of the 102 wells considered 30% had soil gas CH4 at the soil surface that was significantly greater than their respective control. Conversely, 39% of well sites had significant lower surface soil gas CH4 concentrations than their respective control. We interpret elevated soil gas CH4 concentrations to be the result of well integrity failure, but do not know the source of the gas nor the route to the surface. Where elevated CH4 was detected it appears to have occurred within a decade of it being drilled. The flux of CH4 from wells was 364 ± 677 kg CO2eq/well/year with a 27% chance that the well would have a negative flux to the atmosphere independent of well age. This flux is low relative to the activity commonly used on decommissioned well sites (e.g. sheep grazing), however, fluxes from wells that have not been appropriately decommissioned would be expected to be higher.

Characterisation of the rat cerebella CB1 receptor using SR141716A, a central cannabinoid receptor antagonist.

We describe the use of SR141716A, a central cannabinoid antagonist, in radioligand binding and adenylyl cyclase (AC) inhibition studies in rat cerebella membranes. The binding of [3H]SR141716A was dose-dependent and saturable, with Kd and Bmax of 0.61 +/- 0.12 nM and 1752 +/- 294 fmol/mg protein, respectively. Kinetic analysis of [3H]SR141716A binding afforded a Kd of 0.72 nM. In addition [3H]SR141716A was displaced dose-dependently by unlabelled SR141716A yielding a pKi of 8.37 +/- 0.07. Cannabinoid receptor agonists displaced [3H]SR141716A in a dose-dependent manner, (pKi) nabilone (8.29 +/- 0.08), WIN 55,212-2 (7.75 +/- 0.15), delta 9-tetrahydrocannabinol (7.29 +/- 0.21), delta 8-tetrahydrocannabinol (6.53 +/- 0.09) and anandamide (5.92 +/- 0.04). The affinity of anandamide was increased (6.26 +/- 0.13) by co-incubation with a serine protease inhibitor. A range of 13 commonly used non-cannabinoid ligands included at 100 microM were unable to displace [3H]SR141716A. WIN 55,212-2 inhibited basal cAMP formation dose-dependently with a pIC50 of 7.61 +/- 0.12 (24.3 nM) in an SR141716A (1 microM) reversible manner.

Cost analysis of the treatment of schizophrenia in the UK. A simulation model comparing olanzapine, risperidone and haloperidol.

OBJECTIVE: To compare the costs of 2 atypical drug therapies (olanzapine and risperidone) with one another and with a conventional antipsychotic (haloperidol) in the treatment of schizophrenia. DESIGN AND SETTING: The analysis is based on a simulation model with parameter values taken mainly from clinical trial data in patients with schizophrenia, and was conducted within a UK context. RESULTS: The 3 therapies are approximately cost neutral over a 5-year period (olanzapine 35,701 Pounds, risperidone 36,590 Pounds and haloperidol 36,653 Pounds). There is evidence of greater efficacy with the atypical drugs [average percentage of 5 years with Brief Psychiatric Rating Scale (BPRS) scores < 18: olanzapine 63.6%, risperidone 63.0% and haloperidol 52.2%]. The cost and efficacy differences between the 2 atypical drugs are too small to rank them in terms of cost effectiveness. Extensive sensitivity analysis does not change any of the main conclusions. CONCLUSIONS: Given evidence of efficacy gains to the atypical drugs, these represent cost-effective treatment options. Prospective data from nontrial treatment settings would help substantiate the model findings.

Cost analysis of the treatment of schizophrenia in the UK: a comparison of olanzapine and haloperidol.

A decision-tree simulation model is used to examine the costs associated with olanzapine versus haloperidol in the treatment of patients with schizophrenia in the UK. Parameter values and outcome scores were derived mainly from an international clinical trial. Resource consequences were examined on the basis of assumed service delivery and actual unit costs specific to the UK. While olanzapine is more expensive to prescribe than haloperidol, it generates savings by reducing utilisation of medical services. As a result, a comparison of the 2 drugs is approximately cost neutral. Model uncertainties are examined using extensive sensitivity analysis; in most scenarios, cost-neutral results are maintained. Olanzapine is more effective than haloperidol as measured by Brief Psychiatric Rating Scale scores and non-relapse rates. With such gains in effectiveness and near equivalence in terms of costs, olanzapine, in comparison with haloperidol, may represent a cost-effective treatment option.

Patient education literature and help seeking behaviour: perspectives from an evaluation in the United Kingdom.

Decisions by patients upon when to use health care services are a major influence on the consumption of health care resources. Patient education--often based upon written information on how to identify symptoms of common illnesses, when to seek help and how to self-treat--is an increasingly popular strategy to rationalise demand. A large body of literature, in evaluating the impact of such written information, has though overlooked the possession or acquisition of comparable publications by respondents in the course of the studies. This study attempted to overcome this limitation in considering the impact of a prominent patient education booklet that makes reference to over 40 common ailments. Questionnaire data from a cohort sample of residents (n = 495) in an area within which the booklet was circulated and that from a comparison area (n = 509) suggests that such literature exerts a modest influence in orienting patients towards "appropriate" self-referral and self-care behaviour. Reasons for this limited impact emerged however in semi-structured interviews with a sub-sample of respondents (n = 85). These data show that understanding of the way in which written advice for patients is perceived has to focus upon the ways in which diverse sub-populations process and attribute meaning to "official" and "unofficial" sources of advice. More fundamentally, the increasingly sophisticated and specialised nature of medical and scientific knowledge may be distancing expert knowledge from individuals and society such that "lay" responses to "expert" advice now reflect a continuing process of risk assessment, trust or the withholding of trust.

Mental health and stress in the workplace: the case of general practice in the UK.

This study adopted a 'workforce' perspective in a study of job strain in primary care (general practice) in the UK. It explored the level of stress amongst workers in general practice and between practices and examined the relationship between level of stress and work characteristics. Postal questionnaires were sent to a random sample of general practices (n = 81) in southern England. The study showed that 23% of all responders could be classified, according to the GHQ-12, as suffering from mental distress with practice managers having the highest level of stress and clerical and administrative staff the lowest. Work characteristics as measured by Karasek's Job Content Instrument were shown to be significant predictors of job stress as were marital status and health status. The implications of these findings are discussed, particularly focusing on the value of the job strain model for explaining job stress in general practice.

The flux of radionuclides in flowback fluid from shale gas exploitation.

This study considers the flux of radioactivity in flowback fluid from shale gas development in three areas: the Carboniferous, Bowland Shale, UK; the Silurian Shale, Poland; and the Carboniferous Barnett Shale, USA. The radioactive flux from these basins was estimated, given estimates of the number of wells developed or to be developed, the flowback volume per well and the concentration of K (potassium) and Ra (radium) in the flowback water. For comparative purposes, the range of concentration was itself considered within four scenarios for the concentration range of radioactive measured in each shale gas basin, the groundwater of the each shale gas basin, global groundwater and local surface water. The study found that (i) for the Barnett Shale and the Silurian Shale, Poland, the 1 % exceedance flux in flowback water was between seven and eight times that would be expected from local groundwater. However, for the Bowland Shale, UK, the 1 % exceedance flux (the flux that would only be expected to be exceeded 1 % of the time, i.e. a reasonable worst case scenario) in flowback water was 500 times that expected from local groundwater. (ii) In no scenario was the 1 % exceedance exposure greater than 1 mSv-the allowable annual exposure allowed for in the UK. (iii) The radioactive flux of per energy produced was lower for shale gas than for conventional oil and gas production, nuclear power production and electricity generated through burning coal.

Oesophageal atresia with cleft lip and palate: a marker for associated lethal anomalies?

An adverse association between oesophageal atresia (OA) and cleft lip-palate (3% incidence) has been reported. The present study analyses outcomes of this rare association at a UK paediatric surgical centre. Hospital charts of newborns diagnosed with OA were reviewed. Demographics, associated anomalies and prognostic classification (after Spitz 1994) were recorded. Mortality rates and causes of death were examined in OA babies with cleft lip-palate. Of 152 patients treated for OA, five babies (3%) had cleft lip-palate. All of these newborns had common variant OA-TEF and were Spitz group II category. Deaths occurred in 3 of 5 patients (60%) in the OA-cleft group compared to only 8 of 147 patients (5%) without clefts (p < 0.005; Fisher's exact test). OA-cleft non-survivors succumbed to tetralogy of Fallot (n = 2) and trisomy 18 (n = 1; treatment withdrawn). Both survivors with cleft lip-palate had features of the VACTERL sequence: one baby also had Goldenhaar syndrome, the other aortic coarctation. These children now attend mainstream school. Although high-quality survival is possible in OA with cleft lip-palate, this rare phenotype is associated with a substantially decreased survival. Rather than causing death directly, the combination of OA and cleft lip-palate appears to be a marker for further lethal anomalies.

Behavioral and biochemical characterization of a mutant mouse strain lacking D-amino acid oxidase activity and its implications for schizophrenia.

D-amino acid oxidase (DAO) degrades D-serine, a co-agonist at the NMDA receptor (NMDAR). Hypofunction of the NMDAR has been suggested to contribute to the pathophysiology of schizophrenia. Intriguingly, DAO has been recently identified as a risk factor for schizophrenia through genetic association studies. A naturally occurring mouse strain (ddY/DAO-) has been identified which lacks DAO activity. We have characterized this strain both behaviorally and biochemically to evaluate DAO as a target for schizophrenia. We have confirmed that this strain lacks DAO activity and shown for the first time it has increased occupancy of the NMDAR glycine site due to elevated extracellular D-serine levels and has enhanced NMDAR function in vivo. Furthermore, the ddY/DAO- strain displays behaviors which suggest that it will be a useful tool for evaluation of the clinical benefit of DAO inhibition in schizophrenia.

Ambient air, oxygen and nitrox effects on cognitive performance at altitude.

The effects on cognitive performance of breathing air, oxygen and nitrox gas mixtures at surface ambient pressures were investigated during an expedition to the Everest region of Nepal. A slight improvement in grammatical reasoning at altitude was found under nitrox (p < 0.05) and mathematical reasoning showed improvement at altitude on air (p < 0.05), oxygen (p < 0.01) and nitrox (p < 0.01). There were non-significant trends towards decreasing mathematical ability, coupled with an increase in variance on both grammatical and mathematical test performance, with increasing pO2 (all p > 0.05). The results suggest that there is a subtle interaction on cognition as indicated by a significant three-way interaction between subject x altitude x gas (p < 0.05).

Sulphonylurea-sensitive channels and NO-cGMP pathway modulate the heart rate response to vagal nerve stimulation in vitro.

Sulphonylurea-sensitive K(+)channels (K(ATP)) have been implicated in the release of acetylcholine (ACh) from the vagus nerve in the heart. Our aim was to establish the functional significance of this and to test whether this modulation could interact with stimulation of the NO-cGMP pathway that facilitates the decrease in heart rate (HR) in response to vagal nerve stimulation (VNS). We studied the effect of activation (diazoxide, 100 microM) and inhibition (glibenclamide 30 microM or tolbutamide 5 microM) of K(ATP)channels, and activation of the NO-cGMP pathway with the NO donor, sodium nitroprusside (SNP, 20 microM) or the cGMP analogue, 8-Br-cGMP (0.5 m M) on the HR response to VNS in the isolated guinea pig (Cavia porcellus) double atrial/right vagus preparation (n=40). Tolbutamide increased the bradycardia in response to vagal stimulation at 3 and 5 Hz (P<0.05); effects that were reversed by diazoxide. Glibenclamide also significantly increased the HR response to VNS at 1 and 3 Hz (P<0.05). Diazoxide alone significantly attenuated the HR response to VNS at 5 Hz (P<0.05). Neither glibenclamide nor diazoxide affected the HR response to carbamylcholine (CCh, 50-200 n M). In the presence of a maximal dose of tolbutamide, SNP or 8-Br-cGMP further increased the HR response to VNS at 5 Hz (P<0.05). These results are consistent with the hypothesis that inhibition of sulphonylurea-sensitive channels can increase the HR response to VNS by a pre-synaptic mechanism, and that this modulation may be independent of activation of the NO-cGMP pathway.

Pharmacist-managed allergy desensitization program.

A pharmacist-managed immunotherapy program for ambulatory atopic patients is described. Pharmacists in a network of three health centers recommended that they assume management of the allergy desensitization program when they recognized problems with the existing program. Guidelines for the immunotherapy service were developed and approved by the pharmacy, therapeutics, and standing orders committee. Patients, already tested by an allergist, are referred to the pharmacists for the administration of their immunotherapy. Under the guidelines for the program, pharmacists collect and record the patients' history, assess the patients' knowledge of allergy desensitization, administer the allergens, examine the injection site, question the patients about symptoms, and initiate treatment of local and systemic reactions. A physician is available for consultation and for treatment of life-threatened adverse reactions. Following any reaction, the pharmacist adjusts the next antigen dose accordingly. Typical charges for these services are $10-15 for the first visit, and $3.50 for subsequent visits. The pharmacists spend about 30 minutes of their time for the initial visits, and 10 minutes for subsequent visits. The time spent by physicians is negligible, and there is no charge for their consultations. Patients under the care of the pharmacists rarely wait more than 15 minutes for an appointment. This service has been well accepted by patients, physicians, and mid-level practitioners. Pharmacists are using their knowledge and skills to provide a direct patient-care service, and they are being reimbursed for a nondispensing activity.

Pseudoainhum in chronic psoriasis.

Pseudoainhum is a term used to describe the presence of constricting bands of the extremities due to a variety of underlying causes. Progression of the lesions can cause irreversible damage and autoamputation of the affected digit. This report documents a rare association of pseudoainhum and psoriasis and emphasizes the importance of recognizing this condition.