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.

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.

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.

Lessons learned from the development and implementation of a patient-reported outcome and experience measure (POEM) in an Australian glaucoma practice.

BACKGROUND: A patient's perception of how their glaucoma is managed will influence both adherence to their medication and outcome measures such as quality of life. METHODS: Prospective consecutive study using a Glaucoma Patient-reported Outcome and Experience Measure (POEM) modified for an Australian ophthalmic private clinical practice setting. The Australian Glaucoma POEM consists of eight items related to the patient's understanding of the diagnosis and management, acceptability of the treatment, whether they feel their glaucoma is getting worse, interfering with their daily life and concerns regarding loss of vision as well as addressing whether they feel safe under the care of their glaucoma team and how well their care is organised. RESULTS: Two hundred and two patients (M:F 91:111) participated in the study. Mean ± standard deviation for subject age was 69 ± 13 years. Patient's overall perception of their treatment and outcome was favourable. Younger patients felt their glaucoma interfered more with their daily lives and were more worried about losing vision from glaucoma. The greater the number of medications in use, the more they felt their glaucoma was getting worse and that glaucoma interfered with their daily lives. With all other variables accounted for by the multivariate linear model, female patients more strongly agreed that they understood their glaucoma diagnosis and glaucoma management. The patients with a severe visual defect in their worse eye, reported a greater perceived understanding of their glaucoma diagnosis and management and that they felt that glaucoma had a greater interference on their daily life. They were also more concerned about losing vision from glaucoma than their fellow glaucoma patients with less severe or no visual field deficit in the worse eye. CONCLUSIONS: The modified POEM demonstrates potential to capture the concerns of a practice's glaucoma cohort with a view to enhancing the quality of glaucoma care delivered.

Managing corneal foreign bodies in office-based general practice.

BACKGROUND: Patients with a corneal foreign body may first present to their general practitioner (GP). Safe and efficacious management of these presentations avoids sight-threatening and eye-threatening complications. Removal of a simple, superficial foreign body without a slit lamp is within The Royal Australian College of General Practitioners' (RACGP's) curriculum and scope of practice. Knowing the rele-vant procedural skills and indications for referral is equally important. OBJECTIVE: The objective of this article is to provide an evidence-based and expert-based guide to the management of corneal foreign bodies in the GP's office. DISCUSSION: History is key to identifying patient characteristics and mechanisms of ocular injury that are red flags for referral. Examination tech-niques and methods of superficial foreign body removal without a slit lamp are outlined, as well as the procedural threshold for referral to an ophthalmologist.

Information theory and artificial grammar learning: inferring grammaticality from redundancy.

In artificial grammar learning experiments, participants study strings of letters constructed using a grammar and then sort novel grammatical test exemplars from novel ungrammatical ones. The ability to distinguish grammatical from ungrammatical strings is often taken as evidence that the participants have induced the rules of the grammar. We show that judgements of grammaticality are predicted by the local redundancy of the test strings, not by grammaticality itself. The prediction holds in a transfer test in which test strings involve different letters than the training strings. Local redundancy is usually confounded with grammaticality in stimuli widely used in the literature. The confounding explains why the ability to distinguish grammatical from ungrammatical strings has popularized the idea that participants have induced the rules of the grammar, when they have not. We discuss the judgement of grammaticality task in terms of attribute substitution and pattern goodness. When asked to judge grammaticality (an inaccessible attribute), participants answer an easier question about pattern goodness (an accessible attribute).

In control? IQC consensus and statutory regulation.

Purpose - Internal quality control (IQC) represents an essential risk management tool within the total testing pathway (TTP) that contributes to the overall objective of assuring the quality of results produced in medical laboratories. Controlling analytical phase quality alone requires significant expertise and input by scientifically trained staff. This effort has escalated exponentially following the publication of the International Organisation for Standardisation (ISO)15189:2012 requirements for quality and competence in medical laboratories. The reported inconsistency and diversity to IQC approaches in diagnostic laboratories is definitive evidence that international guidance in IQC programme design and implementation is long overdue. The paper aims to discuss these issues. Design/methodology/approach - Herein, the authors define, describe and critically examine the essential elements four stages of an IQC programme and suggest a template to inform both design and ease of implementation. For practical application, the authors have stratified the proposed methodology into four stages: staff education and training; IQC material; IQC targets; and IQC procedure, and provide recommendations that meet ISO15189:2012 requirements. Findings - These recommendations are informed by the published literature together with the collective experience working in clinical biochemistry and diagnostic endocrinology laboratories. The authors note that the laboratory staff's effort on IQC is a continuous process, driven by changes within each IQC stage, in response to risk analysis, maximising economic value or through professional leadership and central to IQC programme implementation and delivery. Practical implications - The authors offer a template that laboratories can use to inform the design and implementation of their IQC programme. Originality/value - The proposed IQC programme is user friendly, flexible and pragmatic with the potential to harmonise practice. The authors have provided a template to potentially harmonise IQC practice nationally. Given the central and critical role that IQC practice plays in ensuring the quality of patient results' importance, the authors contend that the time has come for international consensus and statutory regulation regarding the minimally acceptable criteria for its implementation, monitoring and review.

Laboratory services: regaining and maintaining control.

Purpose - After implementing an internal quality control (IQC) programme, the purpose of this paper is to maintain the requisite analytical performance for clinical laboratory staff, thereby safeguarding patient test results for their intended medical purpose. Design/methodology/approach - The authors address how quality can be maintained and if lost, how it can be regained. The methodology is based on the experience working in clinical laboratory diagnostics and is in accord with both international accreditation requirements and laboratory best practice guidelines. Findings - Monitoring test performance usually involves both prospective and retrospective IQC data analysis. The authors present a number of different approaches together with software tools currently available and emerging, that permit performance monitoring at the level of the individual analyser, across analysers and laboratories (networks). The authors make recommendations on the appropriate response to IQC rule warnings, failures and metrics that indicate analytical control loss, that either precludes further analysis, or signifies deteriorating performance and eventual unsuitability. The authors provide guidance on systematic troubleshooting, to identify undesirable performance and consider risk assessment preventive measures and continuous quality improvement initiatives; e.g., material acceptance procedures, as tools to help regain and maintain analytical control and minimise potential for patient harm. Practical implications - The authors provide a template for use by laboratory scientific personnel that ensures the optimal monitoring of analytical test performance and response when it changes undesirably. Originality/value - The proposed template has been designed to meet the International Organisation for Standardisation for medical laboratories ISO15189:2012 requirements and therefore includes the use of External Quality Assessment and patient results data, as an adjunct to IQC data.

Perfluoroalkyl Cobalt(III) Fluoride and Bis(perfluoroalkyl) Complexes: Catalytic Fluorination and Selective Difluorocarbene Formation.

Four perfluoroalkyl cobalt(III) fluoride complexes have been synthesized and characterized by elemental analysis, multinuclear NMR spectroscopy, X-ray crystallography, and powder X-ray diffraction. The remarkable cobalt fluoride (19)F NMR chemical shifts (-716 to -759 ppm) were studied computationally, and the contributing paramagnetic and diamagnetic factors were extracted. Additionally, the complexes were shown to be active in the catalytic fluorination of p-toluoyl chloride. Furthermore, two examples of cobalt(III) bis(perfluoroalkyl)complexes were synthesized and their reactivity studied. Interestingly, abstraction of a fluoride ion from these complexes led to selective formation of cobalt difluorocarbene complexes derived from the trifluoromethyl ligand. These electrophilic difluorocarbenes were shown to undergo insertion into the remaining perfluoroalkyl fragment, demonstrating the elongation of a perfluoroalkyl chain arising from a difluorocarbene insertion on a cobalt metal center. The reactions of both the fluoride and bis(perfluoroalkyl) complexes provide insight into the potential catalytic applications of these model systems to form small fluorinated molecules as well as fluoropolymers.

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.

Cobalt fluorocarbenes: cycloaddition reactions with tetrafluoroethylene and reactivity of the perfluorometallacyclic products.

Cobalt fluorocarbene complexes CpCo(═CFR(F))(PPh2Me) (Cp = η(5)-C5H5, R(F) = F or CF3) react with tetrafluoroethylene to give the metallacyclobutanes CpCo(κ(2)-CFR(F)CF2CF2-)(PPh2Me) in the first examples of cycloaddition reactions between perfluoroalkenes and metal perfluorocarbenes. The metallacyclic products undergo a variety of reactions upon activation of the C-F bonds, including Brønsted acid-catalyzed C-F/Co-C scrambling. Implications for metal-catalyzed metathesis and polymerization of perfluoroalkenes are discussed.

Metal-free borylative ring-opening of vinyl epoxides and aziridines.

A rational approach towards the borylative ring-opening of vinylepoxides and vinylaziridines, by the in situ formed MeO(-)→bis(pinacolato)diboron adduct, has been developed. The enhanced nucleophilic character of the Bpin (sp(2)) moiety from the reagent favours the SN2' conjugated B addition with the concomitant opening of the epoxide and aziridine rings. The reaction proceeds with total chemoselectivity towards the polyfunctionalised (-OH or -NHTs) allyl boronate. Theoretical calculations have determined the transition states that come from the reaction of the vinylic substrates with the activated MeO(-)→bis(pinacolato)diboron adduct, and a plausible mechanism for the organocatalytic borylative ring opening reaction has been suggested.