An appraisal of the practice of duplicate testing for the detection of irregular analytical errors.

OBJECTIVES: Our study aimed to determine the usefulness of duplicate testing in identifying irregular analytical errors and subsequent prevention of patient mismanagement. METHODS: In our laboratory, all requests for Na+, Ca2+, alkaline phosphatase (ALP), and high-sensitivity cardiac-troponin-I (hs-cTnI) are run in duplicate. Data from four separate weeks for Na+ (n=21,649), Ca2+ (n=14,803) and ALP (n=19,698); and a full year for hs-cTnI (n=17,036) were gathered. For each test, pre-defined limits for differences between duplicates were used to identify erroneous results (Fliers). We further characterised a subset of such fliers as "critical errors", where duplicates fell on opposing sides of a reference/decision making threshold. The costs/benefits of running these tests in duplicate were then considered in light of increased number of tests analysed by this approach. RESULTS: For Na+, 0.03 % of duplicates met our flier defining criteria, and 0.01 % of specimens were considered critical errors. For Ca2+ requests, 4.58 % of results met our flier defining criteria and 0.84 % were critical errors. For ALP, 0.22 % of results were fliers, and 0.01 % were critical errors. For hs-cTnI, 1.58 % of results were classified as fliers, whilst 0.14 % were classified as a critical error. Depending on the test in question, running all analyses in duplicate increased annual costs by as little as €1,100 (for sodium), and as much as €48,000 (for hs-cTnI). CONCLUSIONS: Duplicate testing is effective at identifying and mitigating irregular laboratory errors, and is best suited for assays predisposed to such error, where costs are minimal, and clinical significance of an incorrect result can justify the practice.

Mapping vision loss of patients in a glaucoma backlog following the COVID-19 pandemic: a real-world analysis using the Glauc-Strat-Fast risk stratification tool.

INTRODUCTION: Glauc-Strat-Fast is a clinical tool recommended by The Royal College of Ophthalmologists to classify glaucoma patients into strata of risk for significant future sight loss and an estimate of resource requirement. The aim of this study was to map the movement of glaucoma patients across stratification boundaries on Glauc-Strat-Fast during the COVID-19 pandemic. SUBJECTS AND METHODS: Glauc-Strat-Fast was applied to a consecutive sample of 100 primary open angle glaucoma patients in a backlog at Worcestershire Acute Hospitals NHS Trust. Stratification outcomes were compared between clinic visits prior to the COVID-19 pandemic versus the follow-up visit. Patients were stratified twice separately based on their worse eye (i.e., most affected) and better eye (i.e., least affected) according to Glauc-Strat-Fast. RESULTS: Amount of slippage (difference between target follow-up and actual follow-up) ranged from 2 to 32 months. There was a statistically significant average reduction in visual field mean deviation for better and worse eyes between visits (p = <0.001). At follow-up, no worse eyes were classified as being low risk (green), while 96 were classified as high risk (red). For better eyes, elevation of risk into the highest strata of Glauc-Strat-Fast observed a three-fold increase in patients (19 versus 56) between visits. DISCUSSION: This retrospective real-world analysis highlights patients' movement into the highest strata on the Glauc-Strat-Fast tool and demonstrates a significant deterioration in visual outcomes during a period of extensive appointment slippage. The findings demonstrate the utility of Glauc-Strat-Fast as a tool for improved patient management.

Nitrous Oxide Abuse: Clinical Outcomes, Pharmacology, Pharmacokinetics, Toxicity and Impact on Metabolism.

The recreational use of nitrous oxide (N2O), also called laughing gas, has increased significantly in recent years. In 2022, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) recognized it as one of the most prevalent psychoactive substances used in Europe. Chronic nitrous oxide (N2O) exposure can lead to various clinical manifestations. The most frequent symptoms are neurological (sensitive or motor disorders), but there are also other manifestations like psychiatric manifestations or cardiovascular disorders (thrombosis events). N2O also affects various neurotransmitter systems, leading to its anesthetic, analgesic, anxiolytic and antidepressant properties. N2O is very challenging to measure in biological matrices. Thus, in cases of N2O intoxication, indirect biomarkers such as vitamin B12, plasma homocysteine and plasma MMA should be explored for diagnosis and assessment. Others markers, like oxidative stress markers, could be promising but need to be further investigated.

CAPILLARY LEAK AND EDEMA AFTER RESUSCITATION: THE POTENTIAL CONTRIBUTION OF REDUCED ENDOTHELIAL SHEAR STRESS CAUSED BY HEMODILUTION.

ABSTRACT: Normal shear stress is essential for the normal structure and functions of the microcirculation. Hemorrhagic shock leads to reduced shear stress due to reduced tissue perfusion. Although essential for the urgent restoration of cardiac output and systemic blood pressure, large volume resuscitation with currently available solutions causes hemodilution, further reducing endothelial shear stress. In this narrative review, we consider how the use of currently available resuscitation solutions results in persistent reduction in endothelial shear stress, despite successfully increasing cardiac output and systemic blood pressure. We consider how this reduced shear stress causes (1) a failure to restore normal vasomotor function and normal tissue perfusion thus leading to persistent tissue hypoxia and (2) increased microvascular endothelial permeability resulting in edema formation and impaired organ function. We discuss the need for clinical research into resuscitation strategies and solutions that aim to quickly restore endothelial shear stress in the microcirculation to normal.

Impact analysis of cooperative perception on the performance of automated driving in unsignalized roundabouts.

This paper reports the implementation and results of a simulation-based analysis of the impact of cloud/edge-enabled cooperative perception on the performance of automated driving in unsignalized roundabouts. This is achieved by comparing the performance of automated driving assisted by cooperative perception to that of a baseline system, where the automated vehicle relies only on its onboard sensing and perception for motion planning and control. The paper first provides the descriptions of the implemented simulation model, which integrates the SUMO road traffic generator and CARLA simulator. This includes descriptions of both the baseline and cooperative perception-assisted automated driving systems. We then define a set of relevant key performance indicators for traffic efficiency, safety, and ride comfort, as well as simulation scenarios to collect relevant data for our analysis. This is followed by the description of simulation scenarios, presentation of the results, and discussions of the insights learned from the results.

Spontaneous remission of pendulum swinging thyroid disease in Down syndrome.

Summary: Rare patients who have both thyroid-stimulating hormone (TSH) receptor-stimulating and -blocking antibodies can develop 'pendulum swinging' thyroid dysfunction. A 9-year-old girl with Down syndrome was treated with carbimazole for Graves' disease. After 2 years of treatment, she became profoundly biochemically hypothyroid, and this persisted after carbimazole was discontinued. Low-dose L-thyroxine was commenced. This was subsequently also discontinued as biochemical hyperthyroidism developed. TSH receptor antibody bioassay identified both TSH receptor-stimulating and -blocking antibodies. Mild hyperthyroidism persisted and while consultations regarding definitive treatment were ongoing, medication was not recommenced. Thyroid function normalised spontaneously and she has remained euthyroid for the past 3 years. Previous reports have advised definitive treatment; however, our patient developed spontaneous remission which has been prolonged and definitive therapies have been avoided. It is not yet known how commonly this particular phenomenon occurs. Learning points: Rare patients who have both TSH receptor-stimulating and -blocking antibodies can switch between hyperthyroidism and hypothyroidism or vice versa during treatment with antithyroid drugs or thyroxine. Metamorphic thyroid autoimmunity is more common in Down syndrome. Switching between hyperthyroidism and hypothyroidism and back again is less commonly reported. Definitive treatment such as radioactive iodine or thyroidectomy are usually recommended. Prolonged remission was achieved off all medication, without recourse to definitive treatments.

Visual fields in glaucoma: Where are we now?

Visual fields are an integral part of glaucoma diagnosis and management. COVID has heightened the awareness of the potential for viral spread with the practice of visual fields modified. Mask artefacts can occur due to fogging of the inferior rim of the trail lens. Fortunately, the risk of airborne transmission when field testing is low. The 24-2c may be useful to detect early disease and the 10-2 more sensitive to detect advanced loss. The SITA faster test algorithm is able to reduce testing time thereby improving clinic efficiency, however, may show milder results for moderate or severe glaucoma. The technician has an important role of supervising the visual field performance to achieve reliable output. Home monitoring can provide earlier detection of progression and thus improve monitoring of glaucoma as well as reduce the burden of in-clinic assessments. Artificial Intelligence has been found to have high sensitivity and specificity compared to expert observers in detecting field abnormalities and progression as well as integrating structure with function. Although these advances will improve efficiency and guide accuracy, there will remain a need for clinicians to interpret the results and instigate management.

Current practice of trabeculectomy in a cohort of experienced glaucoma surgeons in Australia and New Zealand.

BACKGROUND/OBJECTIVES: To evaluate current routine trabeculectomy technique preferences among Australian and New Zealand Glaucoma Society surgeons regularly performing trabeculectomy surgery. SUBJECTS/METHODS: Survey of experienced surgeons who perform trabeculectomy. RESULTS: Forty-nine surgeons (33 male:16 female) participated in the survey. Trabeculectomy was performed as day surgery (39/47, 83.0%) under local anesthesia (44/47, 93.6%). The surgical techniques most commonly used were a corneal traction suture (44/47, 93.6%), fornix-based conjunctival flap (43/47, 91.5%) and half-thickness scleral flap (38/47, 81.0%). Mitomycin C antifibrotic agent was used in routine cases by 45/46 (97.8%) surgeons. Surgeons applied the antifibrotic agent under the Tenon layer with a pledget (36/46, 78.2%) with a concentration of 0.02% (37/46, 80.4%) for 2 (11/46, 23.9%) or 3 min (30/46, 65.2%). The Kelly (26/46, 56.5%) and the Khaw Descemet (19/46, 41.3%) punches were used to perform the sclerostomy. Most surgeons performed a peripheral iridectomy in all phakic patients (46/47, 97.9%), but less commonly in pseudophakic patients (34/47, 72.3%). Techniques for closure of the limbal conjunctival edge were quite varied with a combination of suturing including purse string (21/47, 57.4%), wing (20/47, 42.6%) and horizontal mattress sutures (33/47, 70.2%). Surgeons reviewed their routine patients four times in the first month (29/47, 61.7%) and continued the postoperative topical steroids for 3-4 months (28/47, 59.6%). CONCLUSIONS: Although a wide range of techniques for trabeculectomy exists among surgeons, there are consistent procedures currently in use to optimize patient outcomes. This report will assist surgeons in choosing which surgical techniques fit their best practice.

Long-term limitations and complications of trans-scleral diode laser cycloablation for refractory glaucoma.

BACKGROUND: Trans-scleral diode laser cycloablation (cyclodiode) is effective in the short-term management of refractory glaucoma where alternative treatments are not feasible. Long-term outcomes of 5-years or more are not well-documented, particularly in relation to intraocular pressure (IOP) control, need for further procedures and complications such as hypotony and phthisis. METHODS: A review was undertaken of patient medical records with refractory glaucoma who underwent cyclodiode at City Eye Centre in Brisbane from 2012 to 2016. Data included sex, age, laterality, type of glaucoma, cyclodiode parameters, number of glaucoma medications, visual acuity and treatment with acetazolamide. Data were analysed using generalised linear modelling and Kaplan-Meier analysis. RESULTS: A total of 54 eyes in 54 patients (29 M:25F) with a mean age of 66 years (range 15-85 years) with a minimum of 5 years follow up were included. The mean number of burns was 23.3 (range 12-40) over 180-270 degrees, mean power per burn was 1967 mW (range 1500-2000 mW), with a mean duration of 1981 ms (1500-2000 ms). The mean pre-treatment IOP was 31.5 mmHg (range 17-56 mmHg) and mean IOP 5 years post-treatment was 16.1 mmHg (2-42 mmHg). The mean number of pre-treatment medications was 3.6 (range 1-6) and 2.7 (range 0-5) 5 years post treatment, including 5 (8.3%) on oral acetazolamide. Complications of cyclodiode were seen in 6 (11.1%) patients, including 3 (5.0%) cases of hypotony, and 2 (3.3%) phthisis. CONCLUSION: Cyclodiode is often utilised for end-stage glaucoma when the IOP is uncontrolled on medical treatment and drainage surgery is not indicated, resulting in long-term reduction of IOP and the number of medications, including acetazolamide. Hypotony and phthisis can be significant complications.

Only eye study 3 (OnES 3): a qualitative study into how surgeons approach surgery in patients with only one seeing eye.

OBJECTIVE: Performing surgery on an 'only eye' patient is considered high stakes. The purpose of this study is to explore the process of only eye surgery from the perspective of ophthalmic surgeons and improve both patient and surgeon experience. DESIGN, SETTING AND PARTICIPANTS: A cohort of 76 Australian consultant ophthalmologists, divided into three focus groups, were recruited via online webinar to participate in a guided focus group discussion about only eye surgery. Qualitative data regarding participant experience of performing only eye surgery were collected in audio and text form. Thematic analysis was conducted to identify patterns in the data. MAIN OUTCOME MEASURE: Identification of themes relevant to only eye surgery. RESULTS: Five overarching themes relevant to only eye surgery were identified: (1) differences in the surgical decision-making process; (2) differences in the approach to consent, (3) implementation of additional risk reduction strategies, (4) value of having colleagues to discuss and plan surgery with and (5) psychological challenges. A divergent theme was identified: (6) that all surgery, only eye or not, should be treated the same. CONCLUSIONS: This study identifies challenges associated with clinical management of only eye patients across their surgical journey. A conceptual framework to guide surgeons when managing only eye patients is provided which has potential to promote a more unified approach to treating this high-stakes cohort.

Impact of spatiotemporal heterogeneity in COVID-19 disease surveillance on epidemiological parameters and case growth rates.

SARS-CoV-2 case data are primary sources for estimating epidemiological parameters and for modelling the dynamics of outbreaks. Understanding biases within case-based data sources used in epidemiological analyses is important as they can detract from the value of these rich datasets. This raises questions of how variations in surveillance can affect the estimation of epidemiological parameters such as the case growth rates. We use standardised line list data of COVID-19 from Argentina, Brazil, Mexico and Colombia to estimate delay distributions of symptom-onset-to-confirmation, -hospitalisation and -death as well as hospitalisation-to-death at high spatial resolutions and throughout time. Using these estimates, we model the biases introduced by the delay from symptom-onset-to-confirmation on national and state level case growth rates (rt) using an adaptation of the Richardson-Lucy deconvolution algorithm. We find significant heterogeneities in the estimation of delay distributions through time and space with delay difference of up to 19 days between epochs at the state level. Further, we find that by changing the spatial scale, estimates of case growth rate can vary by up to 0.13 d-1. Lastly, we find that states with a high variance and/or mean delay in symptom-onset-to-diagnosis also have the largest difference between the rt estimated from raw and deconvolved case counts at the state level. We highlight the importance of high-resolution case-based data in understanding biases in disease reporting and how these biases can be avoided by adjusting case numbers based on empirical delay distributions. Code and openly accessible data to reproduce analyses presented here are available.

Total plasma homocysteine measurement: Evaluation of the Abbott immunoassay, comparison with the JEOL ion exchange chromatography and investigation of its clinical utility.

Objectives: Homocysteine is an intermediary amino acid formed in methionine metabolism, with elevated total homocysteine (tHCY) being a biomarker of cardiovascular and cerebrovascular diseases. We evaluated the Abbott ARCHITECT tHCY immunoassay, compared it with the current established JEOL ion exchange chromatography (IEC) method and evaluated its clinical utility. Design and methods: Following immunoassay method verification, plasma samples of 91 patients were analysed for tHCY using immunoassay and IEC. Results: For the Abbott immunoassay, accuracy was assessed, with UK NEQAS EQA specimens, by the correlation of our Abbott immunoassay measurements to the Abbott ARCHITECT immunoassay mean (bias = 1.6%), and to the overall immunoassay mean (bias = 2.0%). The total imprecision was 2.7% (11.00 µmol/L), 2.4% (16.80 µmol/L) and 2.8% (24.30 µmol/L) respectively. Bias in linearity assessment was 0.12%-2.58%. The inter-method correlation was strong in Passing-Bablok regression: immunoassay = IEC x0.857 + 2.445 (95% CI: slope = [0.742,0.947], intercept = [1.340,3.582]), with Spearman correlation = 0.803 (p < 0.001). The Bland-Altman plot showed an average difference of -0.284 µmol/L (95% CI: [-1.043,0.474]) with limits of agreement (mean ± 1.96SD) from -7.425 µmol/L to 6.857 µmol/L.No significant difference in tHCY was found using both methods in patients with cerebrovascular diseases and cardiovascular diseases. Most tHCY measurements were within the reference ranges of both methods. All homocystinuria patients had tHCY values above the reference ranges of both methods. Conclusions: The immunoassay demonstrated robust performance in its verification and showed good comparability with the IEC but with some biases so caution is needed if both are used interchangeably. The immunoassay offers an automated alternative to IEC in the assessment of hyperhomocysteinaemia.

Amniotic Membrane-Covered Conformer and Fibrin Glue for Toxic Epidermal Necrolysis.

PURPOSE: Stevens-Johnson syndrome and its more severe form, toxic epidermal necrolysis, are immunologic disorders that cause widespread blistering of the skin and mucous membranes. Its incidence is higher in children and can lead to long-term disabling ocular surface complications that can be averted with amniotic membrane transplantation early in the disease. To introduce an amniotic membrane treatment technique that is time efficient and minimally invasive but still allows for extensive coverage of the ocular mucosal surfaces to prevent and lessen the severity of the complications from ocular surface sequelae. METHODS: The procedure was undertaken in the operating room under general anesthesia. Symblephara were divided before an amniotic membrane-covered conformer was placed into the fornices. Fibrin glue was used to secure the conformer and to keep the palpebral aperture closed. Topical chloramphenicol 0.5% and prednisolone 0.5% were prescribed 4 times a day. RESULTS: After 7 days, the conformers were removed and new amniotic membrane-covered conformers were reapplied in both eyes for a further week. After the second round of treatment, the conformers were left out for 3 days. Inferior symblephara reformed in the left lower fornix, and therefore, a third round of treatment was undertaken in the left eye only, which was then removed after 7 days. A follow-up at 8 weeks revealed 20/20 vision with minimal symblephara in either eye. CONCLUSIONS: This novel technique, using an amniotic membrane-covered conformer in combination with fibrin glue, allows for the coverage of the entire ocular surface and protection of the lid margins while requiring minimal preparation and surgical time. This technique could also be used in patients with other cicatrizing ocular surface conditions, such as chemical or thermal injuries or postreconstructive surgery of the fornices.

Barely sufficient practices in scientific computing.

The importance of software to modern research is well understood, as is the way in which software developed for research can support or undermine important research principles of findability, accessibility, interoperability, and reusability (FAIR). We propose a minimal subset of common software engineering principles that enable FAIRness of computational research and can be used as a baseline for software engineering in any research discipline.