False Positive Referrals Research Articles

Managing ocular pathology in the community & ensuring competency (minor eye conditions, glaucoma, independent prescribing)

In the United Kingdom there is a plethora of enhanced schemes that are funded by the National Health Service (NHS), where specially trained optometrists manage ocular pathology in the community. These will be summarised, including the need to ensure competency and quality.Minor Eye Conditions Services (MECS) provide a symptom‐led appointment to investigate conditions such as red eye, ocular discomfort/pain, blurred vision, and flashes or floaters. Patients may be self‐referred or referred from general medical practitioners, pharmacists, NHS nationwide helpline, or other optometrists. In some geographical areas, patients with these symptoms cannot access hospital eye casualty unless they have first been examined under MECS. MECS optometrists need to undergo accreditation, which includes distance‐learning and practical skills.If there is suspicion of glaucoma following a routine eye examination, repeat or further investigations by community optometrists are commonly funded by the NHS to reduce the number of false positive referrals into secondary care. This is often a prerequisite to a hospital appointment. Less commonly, glaucoma management is being shared with community optometrists in stable or low risk clinical cases. These optometrists are required to have additional, specialised accreditation.Cataract community‐based pre‐operative assessments, which include a discussion about the risks and benefits of surgery for the individual patient, are funded by the NHS in some areas of the UK to reduce false positive referrals. Cataract post‐operative care is increasingly provided in the community for uncomplicated cases to relieve hospital capacity.Optometrists in the UK can undertake an independent prescribing qualification, enabling them to prescribe any licensed medicine for conditions affecting the eye and surrounding tissues. The qualification typically takes one to two years and involves theoretical and practical study and examinations, in addition to supervised clinical experience. Depending on geographical location, optometrists may be able to provide NHS‐funded prescriptions under a local scheme.In addition to the advantages of releasing hospital capacity and decreasing the number of false positive referrals, these schemes provide convenient, local, and timely care to patients, often with evening and weekend appointment availability.These schemes are, unfortunately, not funded nationally across England, resulting in considerable variation in the availability and characteristics of schemes. Furthermore, accreditation requirements differ depending on geographical location. Limited NHS IT infrastructure creates another disadvantage, resulting in a lack of communication between primary and secondary care, especially with referral feedback, and even between optometrists providing basic and enhanced services.Community optometry enhanced services were necessitated in the UK by the modest numbers of ophthalmologists per capita and ageing population with increasing ocular pathology. The use of these schemes increased during and after the COVID pandemic. There have been major benefits in accessibility to eye care services and in increasing the capacity of hospital clinicians for managing the more serious or complex cases that cannot be managed in the community.

An education-based intervention investigating the accuracy of community-based optometrists evaluating limbal anterior chamber depth.

In the UK, referrals for suspected primary angle closure (PAC) by community-based optometrists (CBO) to the hospital eye service show moderate accuracy. This study aimed to assess the interobserver agreement of limbal anterior chamber depth (LACD) between CBOs and ophthalmologists and evaluate the impact of an education intervention. Using a 7-point LACD grading scale, consultant ophthalmologists graded an LACD image dataset developed from 100 patients attending Moorfields Eye Hospital. Two sets of 84 images were utilised for two LACD online assessments. CBO were recruited and undertook assessments before and after a PAC education package (EP) between August 2023 and January 2024. Fifty-two optometrists completed the initial LACD assessment with a median of 19.0 (IQR 9.3-24.8) years post-registration experience. Using the 7-point LACD grading scale, mean weighted kappa (Kw) for pre-EP was moderate, 0.42 (95% CI, 0.36-0.48), increasing to 0.47 (0.42-0.53) post-EP. Conversion to the 4-point grading scale, Kw was substantial, pre-EP 0.61, (0.56-0.66) and post-EP Kw 0.64 (0.58-0.69). An LACD threshold (<25%) sensitivity and specificity pre-EP was 86.0% (79.9-91.3%) and 84.6 (82.3-86.9), respectively. Post-EP sensitivity decreased to 78.2% (74.1-85.1%) (p = 0.049) but specificity increased to 90.4 (88.1-92.8) (p < 0.001). The 4-point LACD grading scale would be more applicable for a case-finding setting. An accessible EP improved agreement and specificity using the joint Royal College of Ophthalmologists/College of Optometrists PAC referral threshold. This EP may reduce false positive PAC referrals and could be rapidly disseminated to CBO. Further research is needed to assess real-world PAC referrals after an education intervention.

A Novel Optometry-Led Decision-Making Community Referral Refinement Scheme for Neovascular Age-Related Macular Degeneration Screening.

The prevalence of neovascular age-related macular degeneration (nAMD) continues to increase. Hospital Eye Services are operating above capacity, innovative solutions to minimise the high proportion of false negative referrals, improve the care pathway and increase capacity for those patients who need ongoing care are essential are essential. A two-phase retrospective longitudinal analysis of all patients referred and assessed for nAMD between; April 2019 to March 2020 (Phase 1) n=394, and April 2020 to March 2021 (Phase 2) n= 414, within Swansea Bay University Health Board (SBUHB). All patients with suspect nAMD were referred to the hospital based nAMD clinic in phase 1, and a community optometry nAMD decision making pathway in phase 2. All clinical records were reviewed, and data collated for subsequent analysis. Age, sex, date of referral, diagnosis, and treatment date were all recorded and analysed. During phase 1, 104 new nAMD cases needing treatment were diagnosed with 85% (n=88) receiving treatment within 2weeks of initial referral. During phase 2, 230 new nAMD cases requiring treatment were diagnosed with 94% (n=216) receiving treatment within 2weeks of initial referral. Both the proportion of nAMD cases diagnosed (χ² = 70.8; p<0.001) and proportion of those treated within 2weeks of initial diagnosis (χ² = 7.57; p<0.05) were significantly higher during phase 2. There are advantages to a community optometry nAMD decision-making pathway with regard to 1) decreasing the number of patients requiring HES attendance, 2) increasing the number of patients able to access treatment for nAMD within 2weeks of initial referral 3) an increased rate of diagnosis confirmation of nAMD and 4) a decrease in the rate of false-positive referrals.

Comment on Dijkstra et al. A False-Negative Newborn Screen for Tyrosinemia Type 1-Need for Re-Evaluation of Newborn Screening with Succinylacetone. Int. J. Neonatal Screen. 2023, 9, 66.

The assessment of newborn screening (NBS) algorithms' performance to ensure quality improvements is a continuous process: false-positive referrals can enable optimisations in the shorter term, but false-negative referrals are often only discovered many years after the screening has taken place [...].

Diagnostic Performance of the Offline Medios Artificial Intelligence for Glaucoma Detection in a Rural Tele-Ophthalmology Setting

PurposeThis study assesses the diagnostic efficacy of offline Medios Artificial Intelligence (AI) glaucoma software in a primary eyecare setting, using non-mydriatic fundus images from Remidio's Fundus-on-Phone (FOP NM-10). AI results were compared with tele-ophthalmologists' diagnoses and with a glaucoma specialist's assessment for those participants referred to tertiary eyecare hospital. DesignProspective, cross-sectional study Participants303 participants from 6 satellite vision centers of a tertiary eye hospital MethodsAt the vision center, participants underwent comprehensive eye evaluations, including clinical history, visual acuity measurement, slit lamp examination, intraocular pressure measurement, and fundus photography using the FOP NM-10 camera. Medios AI-Glaucoma software analysed 42-degrees disc-centric fundus images, categorizing them as normal, glaucoma, or suspect. Tele-ophthalmologists who were glaucoma fellows with a minimum of 3 years of ophthalmology and 1 year of glaucoma fellowship training, masked to AI results, remotely diagnosed subjects based on the history and disc appearance. All participants labelled as disc suspects or glaucoma by AI or tele-ophthalmologists underwent further comprehensive glaucoma evaluation at the base hospital, including clinical examination, Humphrey visual field analysis (HFA), and Optical Coherence Tomography (OCT). AI and tele-ophthalmologist diagnoses were then compared with a glaucoma specialist's diagnosis. Main Outcome MeasuresSensitivity and Specificity of Medios AI ResultsOut of 303 participants, 299 with at least one eye of sufficient image quality were included in the study. The remaining 4 participants did not have sufficient image quality in both eyes. Medios AI identified 39 participants (13%) with referable glaucoma. The AI exhibited a sensitivity of 0.91 (95% CI: 0.71 - 0.99) and specificity of 0.93 (95% CI: 0.89 - 0.96) in detecting referable glaucoma (definite perimetric glaucoma) when compared to tele-ophthalmologist. The agreement between AI and the glaucoma specialist was 80.3%, surpassing the 55.3.% agreement between the tele-ophthalmologist and the glaucoma specialist amongst those participants who were referred to the base hospital. Both AI and the tele-ophthalmologist relied on fundus photos for diagnoses, while the glaucoma specialist's assessments at the base hospital were aided by additional tools such as HFA and OCT. Furthermore, AI had fewer false positive referrals (2 out of 10) compared to the tele-ophthalmologist (9 out of 10). ConclusionMedios offline AI exhibited promising sensitivity and specificity in detecting referable glaucoma from remote vision centers in southern India when compared with teleophthalmologists. It also demonstrated better agreement with glaucoma specialist’s diagnosis for referable glaucoma participants.

The enhanced reliability of higher national institute of health stroke scale thresholds over the conventional 6-point scale

IntroductionIt is still uncertain if higher thresholds on National Institute of Health Stroke Scale (NIHSS) are better predictors of large infarctions than the conventional 6-point cutoff. MethodsWe used 6-point and higher NIHSS thresholds including 8, 9, and 10-point to predict relative infarct areas, expressed as percentage of the affected hemisphere on axial brain computed tomography images, beginning at 5% with 5% increments each time until reaching the 40% cutoff for large infarctions, or achieving 100% sensitivity. Results were compared using area under the receiver operating characteristic curves (AUROC). ResultsWe enrolled 151 patients of acute ischemic stroke (Mean age: 62.88 years ± 12.71; Female: 48.34%). 77 patients (50.99%) exhibited left hemisphere strokes, while 74 (49%) had right hemisphere involvement. Sensitivity values of the 6-point for infarcts measuring 5%, 10%, 20%, 30%, and 40% were 62%, 64%, 77%, 82%, and 100%, respectively. At 40% infarct-size, 8-point achieved comparable results (52%, 55%, 69%, 76%, 100%), closely aligning with the 9-point (50%, 53%, 69%, 76%, 100%). The10-point was slightly trailing behind in sensitivity at 40% infarct-core (96%). Moreover, higher thresholds exhibited improved false-positive rates (FPR). At 40% infarct size, the FPRs of 6, 8, 9, and 10 points were 39%, 27%, 27%, and 21% respectively. Higher thresholds had augmented AUROC values (0.86, 0.86, 0.89) as compared to the 6-point (0.80). Logistic regression identified 14-point as definitive cutoff for large infarctions. ConclusionHigher thresholds can better differentiate small and medium infarcts as true-negatives and substantially reduce false-positive referrals for mechanical thrombectomy.

Evaluating referrals of flashing lights and floaters coming into secondary care from primary care

ABSTRACT Clinical Relevance Optometrists should look to take every opportunity to expand their knowledge, understanding and skills pertaining to vitreoretinal conditions. Background Despite the existence of acute eye care schemes and the up-skilling of optometrists, many units are still noticing large numbers of poor-quality referrals with high false positive rates. The authors pondered whether these schemes are effective. Methods At two different time points, a prospective analysis of patients took place, of all the flashing lights and floaters referrals coming into secondary care at the Royal Glamorgan Hospital, Wales, UK. The following data was captured: the exact source of the primary care referral, the diagnosis being queried, the secondary care diagnoses made and the secondary care management decisions. The accuracy of retinal break and Shafer’s sign detection were also directly compared between primary care and secondary care using Cohen’s Kappa Coefficient. Results For the 2018 period, n = 51 patients were included. For the 2022–23 period n = 100 patients were included. The majority of referrals during both periods were from optometrists (>80%) via the WECS pathway. The most common diagnoses being queried were retinal breaks (~50%), followed by retinal detachments (~20%). Interestingly up to 20% of patients seen in secondary care were diagnosed as normal examinations and ~ 20%. Over 1/3 of patients were discharged after their first visit to the EEC. Statistically significant differences were found between the accuracy of retinal tear and Shafer’s identification between the primary and secondary care settings. Conclusion A high number of false positive referrals are coming into secondary care from the WECS pathway and clear training and education needs have been identified.

Predictors of re-attendance at biennial screening mammography following a false positive referral: A study among women in the south of the Netherlands

AimA false positive (FP) referral after screening mammography may influence a woman's likelihood to re-attend the screening program. The impact of having a FP result in the first or subsequent screening round on re-attendance after a FP result was investigated. In addition, we aimed to study differences in re-attendance rates between women who underwent non-invasive and invasive additional examinations as part of the diagnostic work-up following a FP referral. MethodsA consecutive series of 13,597 women with a FP referral following biennial screening mammography in the south of the Netherlands between 2009 and 2019 was included. ResultsThe screening re-attendance rate was 81.2% after a FP referral, and 91.3% when also including women who had clinical mammographic follow-up. Women who received a FP referral in the first screening round were less likely to re-attend the screening programme in the following three years, compared to those with a FP test in any subsequent round (odds ratio (OR): 0.59, 95%-confidence interval (CI): 0.51–0.69). Women with a FP referral who underwent invasive examinations after referral were less likely to re-attend the screening programme than those who only received additional imaging (OR, 0.48; 95% CI 0.36–0.64). ConclusionWomen with a FP referral are less likely to re-attend the screening programme if this referral occurs at their first screening round or when they undergo invasive diagnostic workup. Hospitals and screening organizations should prioritize informing women about the importance of re-attending the programme following a FP referral.

Artificial intelligence-supported diabetic retinopathy screening in Tanzania: rationale and design of a randomised controlled trial

IntroductionGlobally, diabetic retinopathy (DR) is a major cause of blindness. Sub-Saharan Africa is projected to see the largest proportionate increase in the number of people living with diabetes over the...

Increased Glaucoma Case-Finding Through Routine Optical Coherence Tomography in Optometry Practice.

Optometrists employing OCT as a routine clinical tool have a higher chance of referring patients for specialist glaucoma management than those without OCT. Timely detection of glaucoma is key to preventing or delaying vision loss. This study aimed to assess whether the routine use of optical coherence tomography (OCT) by optometrists for the detection of glaucomatous changes in the optic nerve and retina increased glaucoma referrals to ophthalmologists. This study was a retrospective review of routinely collected electronic medical records of patients from a chain of 331 optometry practices in Australia. Electronic medical records were reviewed for every patient aged 18-99 years who attended an included practice between January 1 and July 31, 2019. Odds of referral for glaucoma assessment were compared between practices performing OCT routinely on all patients (OCT practices, n=175) and without OCT (non-OCT practices, n=20). A subset of referrals were assessed by ophthalmologists to determine the false positive referral rate. The primary outcome measure of this study was referral to an ophthalmologist for glaucoma assessment. A secondary outcome was the rate of false positive referrals, analyzed in a subset of patients referred for glaucoma assessment. Records from 994,461 patients (59% female) were included, and 10,475 (1.1%) were referred for glaucoma assessment. Most referrals were associated with normal intraocular pressure (non-OCT practices: n=496, 66%; OCT practices: n=6,603, 68%). Referral for glaucoma was higher in OCT practices (n=9,719, 1.1%) compared with non-OCT practices (n=756, 0.8%, age-adjusted, gender-adjusted, and location-adjusted odds ratio 1.39, 95% confidence interval 1.10-1.76). Of 318 referred patients (3%, all from OCT practices) for whom ophthalmologist feedback was available, 68 (21%) were considered not to have glaucoma. The routine use of OCT in optometric practice may lead to more timely glaucoma detection and prevention of avoidable vision loss.

Optimizing the Dutch newborn screening for congenital hypothyroidism by incorporating amino acids and acylcarnitines in a machine learning-based model.

Congenital hypothyroidism (CH) is an inborn thyroid hormone (TH) deficiency mostly caused by thyroidal (primary CH) or hypothalamic/pituitary (central CH) disturbances. Most CH newborn screening (NBS) programs are thyroid-stimulating-hormone (TSH) based, thereby only detecting primary CH. The Dutch NBS is based on measuring total thyroxine (T4) from dried blood spots, aiming to detect primary and central CH at the cost of more false-positive referrals (FPRs) (positive predictive value (PPV) of 21% in 2007-2017). An artificial PPV of 26% was yielded when using a machine learning-based model on the adjusted dataset described based on the Dutch CH NBS. Recently, amino acids (AAs) and acylcarnitines (ACs) have been shown to be associated with TH concentration. We therefore aimed to investigate whether AAs and ACs measured during NBS can contribute to better performance of the CH screening in the Netherlands by using a revised machine learning-based model. Dutch NBS data between 2007 and 2017 (CH screening results, AAs and ACs) from 1079 FPRs, 515 newborns with primary (431) and central CH (84) and data from 1842 healthy controls were used. A random forest model including these data was developed. The random forest model with an artificial sensitivity of 100% yielded a PPV of 48% and AUROC of 0.99. Besides T4 and TSH, tyrosine, and succinylacetone were the main parameters contributing to the model's performance. The PPV improved significantly (26-48%) by adding several AAs and ACs to our machine learning-based model, suggesting that adding these parameters benefits the current algorithm.

The effectiveness of interventions for optometric referrals into the hospital eye service: A review.

Ophthalmic services are currently under considerable stress; in the UK, ophthalmology departments have the highest number of outpatient appointments of any department within the National Health Service. Recognising the need for intervention, several approaches have been trialled to tackle the high numbers of false-positive referrals initiated in primary care and seen face to face within the hospital eye service (HES). In this mixed-methods narrative synthesis, we explored interventions based on their clinical impact, cost and acceptability to determine whether they are clinically effective, safe and sustainable. A systematic literature search of PubMed, MEDLINE and CINAHL, guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), was used to identify appropriate studies published between December 2001 and December 2022. A total of 55 studies were reviewed. Four main interventions were assessed, where two studies covered more than one type: training and guidelines (n = 8), referral filtering schemes (n = 32), asynchronous teleophthalmology (n = 13) and synchronous teleophthalmology (n = 5). All four approaches demonstrated effectiveness for reducing false-positive referrals to the HES. There was sufficient evidence for stakeholder acceptance and cost-effectiveness of referral filtering schemes; however, cost comparisons involved assumptions. Referral filtering and asynchronous teleophthalmology reported moderate levels of false-negative cases (2%-20%), defined as discharged patients requiring HES monitoring. The effectiveness of interventions varied depending on which outcome and stakeholder was considered. More studies are required to explore stakeholder opinions around all interventions. In order to maximise clinical safety, it may be appropriate to combine more than one approach, such as referral filtering schemes with virtual review of discharged patients to assess the rate of false-negative cases. The implementation of a successful intervention is more complex than a 'one-size-fits-all' approach and there is potential space for newer types of interventions, such as artificial intelligence clinical support systems within the referral pathway.

Assessment of optometrists' referral accuracy and contributing factors: A review.

In the UK, ophthalmology has the highest number of outpatient appointments within the National Health Service. False-positive referrals from primary care are one of the main factors contributing to the oversubscription of hospital eye services (HESs). We reviewed the accuracy of referrals originating from primary care optometrists and contributing factors, such as condition type and years since registration. Of the 31 studies included in the review, 22 were retrospective analyses of referrals and appointments at the HES. Eight were prospective studies, and one used online clinical vignettes. Seven assessed the accuracy of referrals for all ocular conditions. The remaining studies focused on glaucoma (n = 11), cataracts (n = 7), emergency conditions (n = 4), neovascular age-related macular degeneration (n = 1) and paediatric binocular vision (n = 1). The diagnostic agreement for suspected emergency ocular conditions was the lowest, with only 21.1% of referrals considered to require urgent attention in one study. For glaucoma, the first-visit discharge rate was high (16.7%-48%). Optometrist referral accuracy was overall 18.6% higher than General Medical Practitioners'; however, the two mainly referred different ocular conditions. Female optometrists made more false-positive referrals than males (p = 0.008). The proportion of false positives decreased by 6.2% per year since registration (p < 0.001). There was significant variation in referral accuracy across different ocular conditions, partly due to differences when defining accurate referrals. Optometrists working in primary care are generally more limited in their resources than the HES. Thus, choosing the cautious option of referral when they are unsure could be in the patients' best interests. The possible effect of increased use of advanced imaging on referrals requires evaluation. Although interventions such as refinement schemes have been put in place, these vary across regions, and their approaches such as virtual referral triaging may reduce unnecessary HES face-to-face appointments and promote communication between primary and secondary care.

PD39-09 IMPACT OF PROSTATE IMAGING QUALITY (PI-QUAL) SCORE ON THE DETECTION OF CLINICALLY SIGNIFICANT PROSTATE CANCER IN MEN UNDERGOING MRI-TARGETED BIOPSY

PD39-09 IMPACT OF PROSTATE IMAGING QUALITY (PI-QUAL) SCORE ON THE DETECTION OF CLINICALLY SIGNIFICANT PROSTATE CANCER IN MEN UNDERGOING MRI-TARGETED BIOPSY

Machine learning to improve false-positive results in the Dutch newborn screening for congenital hypothyroidism

ObjectiveThe Dutch Congenital hypothyroidism (CH) Newborn Screening (NBS) algorithm for thyroidal and central congenital hypothyroidism (CH-T and CH-C, respectively) is primarily based on determination of thyroxine (T4) concentrations in dried blood spots, followed by thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) measurements enabling detection of both CH-T and CH-C, with a positive predictive value (PPV) of 21%. A calculated T4/TBG ratio serves as an indirect measure for free T4. The aim of this study is to investigate whether machine learning techniques can help to improve the PPV of the algorithm without missing the positive cases that should have been detected with the current algorithm. Design & methodsNBS data and parameters of CH patients and false-positive referrals in the period 2007–2017 and of a healthy reference population were included in the study. A random forest model was trained and tested using a stratified split and improved using synthetic minority oversampling technique (SMOTE). NBS data of 4668 newborns were included, containing 458 CH-T and 82 CH-C patients, 2332 false-positive referrals and 1670 healthy newborns. ResultsVariables determining identification of CH were (in order of importance) TSH, T4/TBG ratio, gestational age, TBG, T4 and age at NBS sampling. In a Receiver-Operating Characteristic (ROC) analysis on the test set, current sensitivity could be maintained, while increasing the PPV to 26%. ConclusionsMachine learning techniques have the potential to improve the PPV of the Dutch CH NBS. However, improved detection of currently missed cases is only possible with new, better predictors of especially CH-C and a better registration and inclusion of these cases in future models.

Development of a Universal Second-Tier Newborn Screening LC-MS/MS Method for Amino Acids, Lysophosphatidylcholines, and Organic Acids.

First-tier MS-based newborn screening by flow injection analysis can have high presumptive positive rates, often due to isomeric/isobaric compounds or poor biomarker specificity. These presumptive positive samples can be analyzed by second-tier screening assays employing separations such as liquid chromatography-mass spectrometry (LC-MS/MS), which increases test specificity and drastically reduces false positive referrals. The ability to screen for multiple disorders in a single multiplexed test simplifies workflows and maximizes public health laboratories' resources. In this study, we developed and validated a highly multiplexed second-tier method for dried blood spots using a hydrophilic interaction liquid chromatography (HILIC) column coupled to an MS/MS system. The LC-MS/MS method was capable of simultaneously detecting second-tier biomarkers for maple syrup urine disease, homocystinuria, methylmalonic acidemia, propionic acidemia, glutaric acidemia type 1, glutaric acidemia type 2, guanidinoacetate methyltransferase deficiency, short-chain acyl-CoA dehydrogenase deficiency, adrenoleukodystrophy, and Pompe disease.

Factors affecting the accuracy of amyloidosis identification and referral to a specialty centre

Objective Diagnostic algorithms for amyloidosis have evolved over the past decade, particularly with the incorporation of imaging-based techniques to detect amyloid cardiomyopathy. We sought to identify the key sources of amyloidosis misidentification in the community, which lead to false positive referrals to a tertiary centre. Methods We conducted a retrospective review of all referrals to the Amyloidosis Centre from 2010 to 2021 and identified cases lacking amyloid pathology upon final adjudication after extensive assessment at the centre. Factors for false positive referrals were examined. Results Among 2409 referrals of suspected amyloidosis, 147 (6%) demonstrated an absence of amyloid pathology. This percentage increased over time from 4% in 2010 to 13% in 2021. False positive referrals consisted of more people of colour. The most frequent source of inaccuracy was the erroneous staining of tissue specimens with Congo red, followed by suggestive findings on cardiac imaging. In recent years, misinterpretation of 99mtechnetium- pyrophosphate scintigraphy emerged as a major source of false positive referrals. Conclusion Recognising these potential sources of diagnostic error in the workup of amyloidosis can improve patient care. Referral to a centre of excellence for amyloidosis helps confirm an accurate diagnosis and avoid mistreatment.

It Is Time to Rethink Adult Glaucoma Screening Recommendations.

It Is Time to Rethink Adult Glaucoma Screening Recommendations.

Assessment of carnitine excretion and its ratio to plasma free carnitine as a biomarker for primary carnitine deficiency in newborns.

In the Netherlands, newborns are referred by the newborn screening (NBS) Program when a low free carnitine (C0) concentration (<5 μmol/l) is detected in their NBS dried blood spot. This leads to ~85% false positive referrals who all need an invasive, expensive and lengthy evaluation. We investigated whether a ratio of urine C0 / plasma C0 (RatioU:P) can improve the follow-up protocol for primary carnitine deficiency (PCD). A retrospective study was performed in all Dutch metabolic centres, using samples from newborns and mothers referred by NBS due to low C0 concentration. Samples were included when C0 excretion and plasma C0 concentration were sampled on the same day. RatioU:P was calculated as (urine C0 [μmol/mmol creatinine])/(plasma C0 [μmol/l]). Data were available for 59 patients with genetically confirmed PCD and 68 individuals without PCD. The RatioU:P in PCD patients was significantly higher (p value < 0.001) than in those without PCD, median [IQR], respectively: 3.4 [1.2-9.5], 0.4 [0.3-0.8], area under the curve (AUC) 0.837. Classified for age (up to 1month) and without carnitine suppletion (PCD; N= 12, Non-PCD; N= 40), medians were 6.20 [4.4-8.8] and 0.37 [0.24-0.56], respectively. The AUC for RatioU:P was 0.996 with a cut-off required for 100% sensitivity at 1.7 (yielding one false positive case). RatioU:P accurately discriminates between positive and false positive newborn referrals for PCD by NBS. RatioU:P is less effective as a discriminative tool for PCD in adults and for individuals that receive carnitine suppletion.

Improving equity, efficiency and adherence to referral in Pakistan's eye health programmes: Pre- and post-pandemic onset

BackgroundOver one billion people worldwide live with avoidable blindness or vision impairment. Eye Health Programmes tackle this by providing screening, primary eye care, refractive correction, and referral to hospital eye services. One point where patients can be lost in the treatment journey is adherence to hospital referral.ContextPeek Vision's software solutions have been used in Pakistan with the goal of increasing eye health programme coverage and effectiveness. This involved collaboration between health system stakeholders, international partners, local community leaders, social organizers and “Lady Health Workers”.ResultsFrom the beginning of the programmes in November 2018, to the end of December 2021, 393,759 people have been screened, 26% of whom (n = 101,236) needed refractive services or secondary eye care, and so were referred onwards to the triage centers or hospital services. Except for a short period affected heavily by COVID-19 pandemic, the programmes reached an increasing number of people over time: screening coverage improved from 774 people per month to over 28,300 people per month. Gathering and discussing data regularly with stakeholders and implementers has enabled continuous improvement to service delivery. The quality of screening and adherence to hospital visits, gender balance differences and waiting time to hospital visits were also improved. Overall attendance to hospital appointments improved in 2020 compared to 2019 from 45% (95% CI: 42–48%) to 78% (95% CI: 76–80%) in women, and from 48% (95% CI: 45–52%) to 70% (95% CI: 68–73%) in men. These patients also accessed treatment more quickly: 30-day hospital referral adherence improved from 12% in 2019 to 66% in 2020. This approach helped to utilize refractive services more efficiently, reducing false positive referrals to triage from 10.6 to 5.9%. Hospital-based services were also utilized more efficiently, as primary eye care services and refractive services were mainly delivered at the primary healthcare level.DiscussionDespite various challenges, we demonstrate how data-driven decisions can lead to health programme systems changes, including patient counseling and appointment reminders, which can effectively improve adherence to referral, allowing programmes to better meet their community's needs.