Red filter meibography by smartphones in patients with meibomian gland dysfunction: a validity and reliability study.

OBJECTIVE: The objective of this study is to determine the validity and reliability of the red filter meibography by smartphone compared with infrared in assessing meibomian gland drop-out. METHODS AND ANALYSIS: An analytical cross-sectional study was done with a total of 35 subjects (68 eyes) with suspected MGD based on symptoms and lid morphological abnormalities. Meibomian glands were photographed using two smartphones (Samsung S9 and iPhone XR) on a slit-lamp with added red filter. Images were assessed subjectively using meiboscore by the two raters and drop-out percentages were assessed by ImageJ. RESULTS: There was no agreement in meiboscore and a minimal level of agreement in drop-out percentages between red filter meibography and infrared. Inter-rater reliability showed no agreement between two raters. Intra-rater reliability demonstrated weak agreement in rater 1 and no agreement in rater 2. CONCLUSION: Validity of the red filter meibography technique by smartphones is not yet satisfactory in evaluating drop-out. Further improvement on qualities of images must be done and research on subjective assessment was deemed necessary due to poor results of intrarater and inter-rater reliability.

A benefit risk approach in cutoff determination for diagnostic tests.

A crucial step in the design of a diagnostic test is determining the cutoff point, the threshold which separates a negative measurement from a positive one. The results of a diagnostic test have clinical consequences: only when disease is accurately detected, proper treatments be administered, and vice versa. Benefit-Risk (BR) analysis should be used to determine the optimal cutoff point that optimizes the consequence. Quantitative BR analysis requires measurable benefit and risk and a function, e.g., linear or ratio, to combine all the components. When BR corresponding to the four possible diagnostic test outcomes are all scaled in units of risk resulting from an untreated disease, we propose a net BR (linear BR) equation as a function of diagnostic parameters, disease prevalence, benefit of correct diagnosis and risk of false diagnostic results. Optimal cutoff of a diagnostic test can be obtained using this function. Comparison of diagnostic tests based on their benefit and risk of tests is also discussed. Use of this function is illustrated with a biosensor rapid antigen test for SARS-CoV-2.

Surveillance of adults with congenital heart disease: Current guidelines and actual clinical practice.

BACKGROUND AND AIM: Congenital heart disease (CHD) is the most common birth defect with prevalence of 0.8%. Thanks to tremendous progress in medical and surgical practice, nowadays, >90% of children survive into adulthood. Recently European Society of Cardiology (ESC), American College of Cardiology (ACC)/ American Heart Association (AHA) issued guidelines which offer diagnostic and therapeutic recommendations for the different defect categories. However, the type of technical exams and their frequency of follow-up may vary largely between clinicians and centres. We aimed to present an overview of available diagnostic modalities and describe current surveillance practices by cardiologists taking care of adults with CHD (ACHD). METHODS AND RESULTS: A questionnaire was used to assess the frequency cardiologists treating ACHD for at least one year administrated the most common diagnostic tests for ACHD. The most frequently employed diagnostic modalities were ECG and echocardiography for both mild and moderate/severe CHD. Sixty-seven percent of respondents reported that they routinely address psychosocial well-being. CONCLUSION: Differences exist between reported current clinical practice and published guidelines. This is particularly true for the care of patients with mild lesions. In addition, some differences exist between ESC and American guidelines, with more frequent surveillance suggested by the Americans.

Atrial Fibrillation Screening During Routine Automated Office, Home, and Ambulatory Blood Pressure Measurement: A Diagnostic Test Accuracy Systematic Review and Meta-Analysis.

BACKGROUND: Atrial fibrillation (AF) is often asymptomatic and undiagnosed. As AF and hypertension often coexist, opportunistic AF detection during routine automated blood pressure (BP) measurement appears to be an attractive screening method. METHODS: A systematic literature search was conducted to identify studies assessing the diagnostic test accuracy of office, home, or 24-hour ambulatory BP measuring devices with AF detection algorithms versus reference electrocardiography. Analyses were performed per participant (AF status based on several BP readings; most office/home devices) or per reading (AF status based on individual readings; all ambulatory devices). A meta-analysis stratified by device type (office/home/ambulatory) was conducted to calculate pooled measures of diagnostic accuracy. Sensitivity/meta-regression analyses were also performed. RESULTS: Among 3096 records initially retrieved, 23 diagnostic test accuracy studies were included. Data derived from 11 093 individuals (weighted age 69 years, males 56%, hypertensives 79%, diabetics 24%, and AF prevalence 17%) indicated a pooled sensitivity 0.97 (95% CI, 0.92-0.99), specificity 0.93 (95% CI, 0.90-0.95), and accuracy 0.93 (95% CI, 0.89-0.95), with generally consistent results using office, home, or ambulatory BP devices (slightly lower specificity with the latter). The positive and negative predictive values were 0.70 (95% CI, 0.60-0.80) and 0.99 (95% CI, 0.98-1.00), respectively. Sensitivity analyses indicated lower specificity in studies implementing reading versus participant analyses. Most studies presented a low risk of bias and minor applicability concerns. CONCLUSIONS: There is considerable and consistent evidence suggesting high diagnostic accuracy of AF detection algorithms implemented in automated BP monitors during routine BP measurements in and out of the office. AF diagnosis requires verification (electrocardiography) before treatment is administered.

Use of in silico approaches, synthesis and profiling of Pan-filovirus GP-1,2 preprotein specific antibodies.

Intermolecular interactions of protein-protein complexes play a principal role in the process of discovering new substances used in the diagnosis and treatment of many diseases. Among such complexes of proteins, we have to mention antibodies; they interact with specific antigens of two genera of single-stranded RNA viruses belonging to the family Filoviridae-Ebolavirus and Marburgvirus; both cause rare but fatal viral hemorrhagic fever in Africa, with pandemic potential. In this research, we conduct studies aimed at the design and evaluation of antibodies targeting the filovirus glycoprotein precursor GP-1,2 to develop potential targets for the pan-filovirus easy-to-use rapid diagnostic tests. The in silico research using the available 3D structure of the natural antibody-antigen complex was carried out to determine the stability of individual protein segments in the process of its formation and maintenance. The computed free binding energy of the complex and its decomposition for all amino acids allowed us to define the residues that play an essential role in the structure and indicated the spots where potential antibodies can be improved. Following that, the study involved targeting six epitopes of the filovirus GP1,2 with two polyclonal antibodies (pABs) and 14 monoclonal antibodies (mABs). The evaluation conducted using Enzyme Immunoassays tested 62 different sandwich combinations of monoclonal antibodies (mAbs), identifying 10 combinations that successfully captured the recombinant GP1,2 (rGP). Among these combinations, the sandwich option (3G2G12* - (rGP) - 2D8F11) exhibited the highest propensity for capturing the rGP antigen.

The role of viral diagnostic tests in respiratory tract infections: moving forward.

The increased knowledge on virology and the increased potential of their diagnostic has risen several relevant question about the role of an early viral diagnosis and potential early treatment on the management of respiratory tract infections (RTI). In order to further understand the role of viral diagnostic tests in the management of RTI, a panel of experts was convened to discuss about their potential role, beyond what had been agreed in Influenza. The objective of this panel was to define the plausible role of aetiologic viral diagnostic into clinical management; make recommendations on the potential expanded use of such tests in the future and define some gaps in the management of RTI. Molecular Infection Viral Diagnostic (mIVD) tests should be used in all adult patients admitted to Hospital with RTI, and in paediatric patients requiring admission or who would be referred to another hospital for more specialised care. The increased use of mIVD will not only reduce the inappropriate use of antibiotics so reducing the antibiotic microbe resistance, but also will improve the outcome of the patient if an aetiologic viral therapy can be warranted, saving resource requirements and improving patient flows. Implementing IVD testing in RTI has various organizational benefits as well, but expanding its use into clinical settings would need a cost-effectiveness strategy and budget impact assessment.

Bronchogenic cyst: a rare cause of palpitations and atrial fibrillation.

Bronchogenic cysts are rare congenital lesions found primarily in the mediastinum. Most patients are asymptomatic and can be treated with minimally invasive resection. We present a case of a middle-aged patient who presented to a district general hospital with palpitations and shortness of breath. She underwent a computerised tomographic pulmonary angiogram that showed a likely bronchogenic cyst and was subsequently transferred to our hospital. She developed atrial fibrillation during admission requiring therapy with beta-blockers and digoxin. Cardiac MRI revealed a large cyst posterior to the left atrium, a moderate circumferential pericardial effusion and bilateral pleural effusions. There was significant left atrial compression. The patient underwent surgical removal of the cyst and was discharged. She returned to the hospital within a week with palpitations and was treated with intravenous antibiotics for sepsis. She was discharged a week later and remained clinically stable.

Systematic scoping review: Use of the faecal immunochemical test residual buffer to enhance colorectal cancer screening.

BACKGROUND: The faecal immunochemical test (FIT) is an inexpensive and convenient modality to screen for colorectal cancer. However, its one-time sensitivity for detecting colorectal cancer and cancer precursors is limited. There is growing interest in using the non-haemoglobin contents of FIT residual buffer to enhance colonic neoplasia detection. AIM: To establish from the literature a framework to catalogue candidate biomarkers within FIT residual buffer for non-invasive colorectal cancer screening. METHODS: The search strategy evaluated PubMed, Scopus, Web of Science, Embase, and Google Scholar for publications through 25 October 2023, with search terms including FIT, buffer, OC-sensor, biomarkers, microbiome, microRNA (miR), colon, rectum, screening, neoplasm, and early detection. Studies employing home-based collection samples using quantitative FIT first processed for haemoglobin were included. One author reviewed all articles; a second author completed a 20% full-text audit to ensure adherence to eligibility criteria. RESULTS: A broad search yielded 1669 studies and application of eligibility criteria identified 18 relevant studies. Multiple protein, DNA/RNA, and microbiome biomarkers (notably haptoglobin, miR-16, miR-27a-3p, miR-92a, miR-148a-3p, miR-223, miR-421, let-7b-5p, and Tyzzerella 4) were associated with colorectal neoplasia. Furthermore, studies highlighted the short-term stability of biomarkers for clinical use and long-term stability for research purposes. CONCLUSIONS: This scoping review summarises the framework and progress of research on stability of biomarkers in FIT residual buffer and their associations with colorectal neoplasia to guide opportunities for further confirmatory studies to enhance colorectal cancer screening.

Usefulness of serial testing for the diagnosis of malaria in cases of fever upon return from travel.

BACKGROUND: When malaria is suspected in case of fever after travel in endemic areas, the current recommendation is to repeat the malaria test at 24-hour intervals, with up to two additional tests, as long as the test result is negative. A retrospective analysis was conducted to investigate the appropriateness of this recommendation by determining the proportion of tests with negative result at first and subsequently with a positive one at second or third attempt. METHODS: A retrospective study was conducted at the Centre for Primary Care and Public Health, Lausanne, covering a period of 15 years. All patients tested once for malaria were included. Testing included microscopy thick and thin films as well as malaria rapid diagnostic test used in combination. The main outcome measure was the proportion of patients with a first negative test result, subsequently positive on second or third test over the total patients with suspected malaria assessed. Demographic, travel, clinical, and laboratory variables were collected from patients' records to identify potential predictors of an initially negative and then positive test result. RESULTS: Four thousand nine hundred seventy-two patients were included. Of those, 4557 (91.7%) had definitive negative test results, and 415 (8.3%) had a positive result on the first test [332/415 (80%) Plasmodium falciparum, 40/415 (9.6%) P. vivax, 21/415 (5.1%) P. ovale, 12/415 (2.9%) P. vivax/ovale, 9/415 (2.2%) P. malariae and 1/415 (0.2%) P. knowlesi], and 3/4972 (0.06%) had a positive result on the second test after a first negative result, 1/4972(0.02%) had a positive test result after 2 negative results, all with P. falciparum. One of the four patients that were positive after their initial negative test was pregnant. The very small number of patients with an initially negative test result and secondarily positive did not allow for risk factor analysis. CONCLUSIONS: The current recommendation of serial malaria testing is not supported by the present study, a fortiori for those who do not present with a strong clinical or laboratory predictor of malaria.

General practitioners' perspectives on diagnostic tests for children: a qualitative interview study.

Background Most healthcare contacts for children in the UK occur in general practice. Diagnostic tests can be beneficial in narrowing differential diagnoses, however, there is substantial variation in the use of tests for children in general practice. Unwarranted variation in testing can lead to variation in quality of care and exacerbate health inequities. No prior study has tried to understand why variation in testing exists for children in general practice. Aim To explore GP perspectives on using diagnostic tests for children in primary care and the underlying drivers of variation. Design and setting Semi-structured interviews were conducted with GPs and trainee GPs in England. Methods We conducted interviews with 18 GPs and 2 trainees between April and June 2023. The interviews were transcribed and analysed thematically. Results GPs reflected that their approach to testing in children differed from adults; their threshold to test was higher, but the threshold to refer to specialists was lower. GPs' perceptions of test utility varied, including objective testing for asthma. Perceived drivers of variation in testing included: 1) intrinsic (clinician) factors relating to their risk tolerance and experience, and 2) extrinsic factors, including disease prevalence, parental concern and expectations of healthcare, workforce changes leading to fragmentation in care, time constraints and differences in guidelines. Conclusions The findings of this study identify actionable issues for clinicians, researchers, and policymakers to address gaps in education, evidence, and guidance, reduce unwarranted differences in test use and improve the quality of health care delivered to children in general practice.

Using artificial intelligence to improve human performance: efficient retinal disease detection training with synthetic images.

BACKGROUND: Artificial intelligence (AI) in medical imaging diagnostics has huge potential, but human judgement is still indispensable. We propose an AI-aided teaching method that leverages generative AI to train students on many images while preserving patient privacy. METHODS: A web-based course was designed using 600 synthetic ultra-widefield (UWF) retinal images to teach students to detect disease in these images. The images were generated by stable diffusion, a large generative foundation model, which we fine-tuned with 6285 real UWF images from six categories: five retinal diseases (age-related macular degeneration, glaucoma, diabetic retinopathy, retinal detachment and retinal vein occlusion) and normal. 161 trainee orthoptists took the course. They were evaluated with two tests: one consisting of UWF images and another of standard field (SF) images, which the students had not encountered in the course. Both tests contained 120 real patient images, 20 per category. The students took both tests once before and after training, with a cool-off period in between. RESULTS: On average, students completed the course in 53 min, significantly improving their diagnostic accuracy. For UWF images, student accuracy increased from 43.6% to 74.1% (p<0.0001 by paired t-test), nearly matching the previously published state-of-the-art AI model's accuracy of 73.3%. For SF images, student accuracy rose from 42.7% to 68.7% (p<0.0001), surpassing the state-of-the-art AI model's 40%. CONCLUSION: Synthetic images can be used effectively in medical education. We also found that humans are more robust to novel situations than AI models, thus showcasing human judgement's essential role in medical diagnosis.

Validation of a deep learning model for automatic detection and quantification of five OCT critical retinal features associated with neovascular age-related macular degeneration.

PURPOSE: To develop and validate a deep learning model for the segmentation of five retinal biomarkers associated with neovascular age-related macular degeneration (nAMD). METHODS: 300 optical coherence tomography volumes from subject eyes with nAMD were collected. Images were manually segmented for the presence of five crucial nAMD features: intraretinal fluid, subretinal fluid, subretinal hyperreflective material, drusen/drusenoid pigment epithelium detachment (PED) and neovascular PED. A deep learning architecture based on a U-Net was trained to perform automatic segmentation of these retinal biomarkers and evaluated on the sequestered data. The main outcome measures were receiver operating characteristic curves for detection, summarised using the area under the curves (AUCs) both on a per slice and per volume basis, correlation score, enface topography overlap (reported as two-dimensional (2D) correlation score) and Dice coefficients. RESULTS: The model obtained a mean (±SD) AUC of 0.93 (±0.04) per slice and 0.88 (±0.07) per volume for fluid detection. The correlation score (R2) between automatic and manual segmentation obtained by the model resulted in a mean (±SD) of 0.89 (±0.05). The mean (±SD) 2D correlation score was 0.69 (±0.04). The mean (±SD) Dice score resulted in 0.61 (±0.10). CONCLUSIONS: We present a fully automated segmentation model for five features related to nAMD that performs at the level of experienced graders. The application of this model will open opportunities for the study of morphological changes and treatment efficacy in real-world settings. Furthermore, it can facilitate structured reporting in the clinic and reduce subjectivity in clinicians' assessments.

Enhanced CT imaging artificial neural network coronary artery calcification score assisted diagnosis.

BACKGROUND: The study of coronary artery calcification (CAC) may assist in identifying additional coronary artery problem protective factors. On the contrary side, due to the wide variety of CAC as individuals, CAC research is difficult. Due to this, evaluating data for investigation is becoming complicated. OBJECTIVE: To use a multi-layer perceptron, we investigated the accuracy and reliability of synthetic CAC coursework or hazard classification in pre or alors chest computerized tomography (CT) of arrangements resolutions in this analysis. method: Photographs of the chest from similar individuals as well as calcium-just and non-gated pictures were incorporated. This cut thickness ordered CT pictures (bunch A: 1 mm; bunch B: 3 mm). The CAC rating was determined utilizing calcification score picture information, and became standard for tests. While the control treatment's machine learning program was created using 170 computed tomography pictures and evaluated using 144 scans, group A's machine learning algorithm was created using 150 chest CT diagnostic tests. RESULTS: 334 external related pictures (100 µm: 117; 0.5 mm x: 117) of 117 individuals and 612 inside design organizing (1 mm: 294; mm3: 314) of 406 patients were surveyed. Pack B had 0.94, however, tests An and b had 0.90 (95% CI: 0.85-0.93) ICCs between significant learning and gold expenses (0.92-0.96). Dull Altman plots agreed well. A machine teaching approach successfully identified 71% of cases in category A is 81% of patients in section B again for cardiac risk class. CONCLUSION: Regression risk evaluation algorithms could assist in categorizing cardiorespiratory individuals into distinct risk groups and conveniently personalize the treatments to the patient's circumstances. The models would be based on information gathered through CAC. On both 1 and 3-mm scanners, the automatic determination of a CAC value and cardiovascular events categorization that used a depth teaching approach was reliable and precise. The layer thickness of 0.5 mm on chest CT was slightly less accurate in CAC detection and risk evaluation.

Lumbar disc herniation: Epidemiology, clinical and radiologic diagnosis WFNS spine committee recommendations.

Objective: To formulate the most current, evidence-based recommendations regarding the epidemiology, clinical diagnosis, and radiographic diagnosis of lumbar herniated disk (LDH). Methods: A systematic literature search in PubMed, MEDLINE, and CENTRAL was performed from 2012 to 2022 using the search terms "herniated lumbar disc", "epidemiology", "prevention" "clinical diagnosis", and "radiological diagnosis". Screening criteria resulted in 17, 16, and 90 studies respectively that were analyzed regarding epidemiology, clinical diagnosis, and radiographic diagnosis of LDH. Using the Delphi method and two rounds of voting at two separate international meetings, ten members of the WFNS (World Federation of Neurosurgical Societies) Spine Committee generated eleven final consensus statements. Results: The lifetime risk for symptomatic LDH is 1-3%; of these, 60-90% resolve spontaneously. Risk factors for LDH include genetic and environmental factors, strenuous activity, and smoking. LDH is more common in males and in 30-50 year olds. A set of clinical tests, including manual muscle testing, sensory testing, Lasegue sign, and crossed Lasegue sign are recommended to diagnose LDH. Magnetic resonance imaging (MRI) is the gold standard for confirming suspected LDH. Conclusions: These eleven final consensus statements provide current, evidence-based guidelines on the epidemiology, clinical diagnosis, and radiographic diagnosis of LDH for practicing spine surgeons worldwide.

Repurposing rapid diagnostic tests to detect falsified vaccines in supply chains.

Substandard (including degraded) and falsified (SF) vaccines are a relatively neglected issue with serious global implications for public health. This has been highlighted during the rapid and widespread rollout of COVID-19 vaccines. There has been increasing interest in devices to screen for SF non-vaccine medicines including tablets and capsules to empower inspectors and standardise surveillance. However, there has been very limited published research focussed on repurposing or developing new devices for screening for SF vaccines. To our knowledge, rapid diagnostic tests (RDTs) have not been used for this purpose but have important potential for detecting falsified vaccines. We performed a proof-in-principle study to investigate their diagnostic accuracy using a diverse range of RDT-vaccine/falsified vaccine surrogate pairs. In an initial assessment, we demonstrated the utility of four RDTs in detecting seven vaccines. Subsequently, the four RDTs were evaluated by three blinded assessors with seven vaccines and four falsified vaccines surrogates. The results provide preliminary data that RDTs could be used by multiple international organisations, national medicines regulators and vaccine manufacturers/distributors to screen for falsified vaccines in supply chains, aligned with the WHO global 'Prevent, Detect and Respond' strategy.

External quality assessment to support the WHO ProSPeRo study for the evaluation of two dual HIV/syphilis point-of-care tests in seven countries.

BACKGROUND: Sexually transmitted infections (STIs) such as syphilis and HIV remain to be a significant public health issue worldwide. Dual rapid point-of-care tests (POCTs) have shown promise for detecting antibodies to HIV and syphilis but have not been fully evaluated in the field. Our study supported the WHO ProSPeRo study on Sexually Transmitted Infection Point-of-Care Testing (STI POCT) by providing external quality assessment (EQA) for HIV and syphilis testing in reference laboratories and their associated clinical sites in seven countries. METHODS: HIV/syphilis serum liquid and dried tube specimen (DTS) panels were prepared by CDC. Liquid panels were distributed to the reference laboratories for three rounds of testing using commercially and locally available laboratory-based serological tests. DTS panels were sent to the clinical testing sites for 8 rounds of POC testing using the Abbott SD BIOLINE HIV/Syphilis Duo test (hereafter referred to as SD BIOLINE) and the Chembio Dual Path Platform (DPP) HIV-Syphilis assay. EQA panels were tested at CDC using the Rapid Plasma Reagin (RPR) test and the Treponema pallidum Particle Agglutination assay (TP-PA) for syphilis antibodies. Genetic Systems HIV-1/HIV-2 Plus O EIA, Geenius HIV Supplemental Assay and the Oraquick Advance HIV test were used to detect HIV antibodies in the EQA panels. Results from the reference laboratories and POCT sites were compared to those obtained at the CDC and a percentage agreement was calculated. RESULTS: Qualitative RPR and TP-PA performed at the reference laboratories demonstrated 95.4-100% agreement with CDC results while quantitative RPR and TP-PA tests demonstrated 87.7% and 89.2% agreement, respectively. A 93.8% concordance rate was observed for qualitative HIV testing in laboratories. EQA testing at clinical sites using dual tests showed 98.7% and 99.1% agreement for detection of HIV antibodies and eight out of 10 sites had > 95.8% agreement for syphilis testing. However, two clinical sites showed only 65.0-66.7% agreement for SD BIOLINE and 84.0-86.7% for DPP, respectively, for syphilis testing. CONCLUSIONS: Overall, laboratories demonstrated high EQA performance in this study. Both HIV/syphilis POCTs gave expected results in the clinic-based evaluations using DTS. However, testing errors were identified in a few testing sites suggesting the necessity for continuous training and monitoring the quality of POC testing.

Diagnostic tests recommended for the clinical assessment of patients with wrist complaints, an e-Delphi study.

BACKGROUND: Evidence-based practice for history-taking and physical examination in the evaluation of wrist complaints is limited. PURPOSE: To create a set of recommended diagnostic tests for the clinical assessment of patients with undifferentiated wrist complaints. STUDY DESIGN: An e-Delphi study, following the recommendations on conducting and reporting Delphi studies, was performed. METHODS: In this e-Delphi study, a national multidisciplinary panel of experts was invited to inventory diagnostic tests, based on several case scenarios, for the probability diagnosis in patients (age ≥18 years) with undifferentiated wrist complaints. Four case scenarios were constructed and presented to the expert panel members, which differed in age of the patient (35 vs 65 years), location (radial vs ulnar), and duration (6 vs 10 weeks) of the complaints. In consecutive rounds, the experts were asked to rate the importance of the inventoried diagnostic tests. Finally, experts were asked to rank recommended diagnostic tests for each case scenario. RESULTS: Merging all results, the following diagnostic tests were recommended for all case scenarios: ask whether a trauma has occurred, ask how the complaints can be provoked, ask about the localization of the complaints, assess active ranges of motion, assess the presence of swelling, assess the difference in swelling between the left and right, assess the deformities or changes in position of the wrist, and palpate at the point of greatest pain. CONCLUSIONS: This is the first scientific study where experts clinicians recommended diagnostic tests when assessing patients with undifferentiated wrist complaints, varying in age of the patient (35 vs 65 years), location (radial vs ulnar), and duration (6 vs 10 weeks).