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Background: Vector-borne diseases (VBDs) impact both human and veterinary medicine and pose special public health challenges. The main bacterial vector-borne pathogens (VBPs) of importance in veterinary medicine include Anaplasma spp., Bartonella spp., Ehrlichia spp., and Spotted Fever Group Rickettsia. Taxon-targeted PCR assays are the current gold standard for VBP diagnostics but limitations on the detection of genetically diverse organisms support a novel approach for broader detection of VBPs. We present a methodology for genetic characterization of VBPs using Next-Generation Sequencing (NGS) and computational approaches. A major advantage of NGS is the ability to detect multiple organisms present in the same clinical sample in an unsupervised (i.e. non-targeted) and semi-quantitative way. The Standard Operating Procedure (SOP) presented here combines industry-standard microbiome analysis tools with our ad-hoc bioinformatic scripts to form a complete analysis pipeline accessible to veterinary scientists and freely available for download and use at https://github.com/eltonjrv/microbiome.westernu/tree/SOP. Results: We tested and validated our SOP by mimicking single, double, and triple infections in genomic canine DNA using serial dilutions of plasmids containing the entire 16 S rRNA gene sequence of (A) phagocytophilum, (B) v. berkhoffii, and E. canis. NGS with broad-range 16 S rRNA primers followed by our bioinformatics SOP was capable of detecting these pathogens in biological replicates of different dilutions. These results illustrate the ability of NGS to detect and genetically characterize multi-infections with different amounts of pathogens in a single sample. Conclusions: Bloodborne microbiomics & metagenomics approaches may help expand the molecular diagnostic toolbox in veterinary and human medicine. In this paper, we present both in vitro and in silico detailed protocols that can be combined into a single workflow that may provide a significant improvement in VBP diagnostics and also facilitate future applications of microbiome research in veterinary medicine. [ABSTRACT FROM AUTHOR]

Background: Multiple imputation has become very popular as a general-purpose method for handling missing data. The validity of multiple-imputation-based analyses relies on the use of an appropriate model to impute the missing values. Despite the widespread use of multiple imputation, there are few guidelines available for checking imputation models. Analysis: In this paper, we provide an overview of currently available methods for checking imputation models. These include graphical checks and numerical summaries, as well as simulation-based methods such as posterior predictive checking. These model checking techniques are illustrated using an analysis affected by missing data from the Longitudinal Study of Australian Children. Conclusions: As multiple imputation becomes further established as a standard approach for handling missing data, it will become increasingly important that researchers employ appropriate model checking approaches to ensure that reliable results are obtained when using this method. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) and schizotypal disorder (SD) both have a heterogenous presentation, with significant overlaps in symptoms and behaviour. Due to elevated recognition and knowledge of ASD worldwide, there is a growing rate of referrals from primary health professionals to specialised units. At all levels of assessment, the differential diagnostic considerations between ASD and SD exert major challenges for clinicians. Although several validated screening questionnaires exist for ASD and SD, none have differential diagnostic properties. Accordingly, in this study, we aim to develop a new screening questionnaire, the schiZotypy Autism Questionnaire (ZAQ), which provides a combined screening for both conditions, while also indicating the relative likelihood of each. Methods: We aim to test 200 autistic patients and 100 schizotypy patients recruited from specialised psychiatric clinics and 200 controls from the general population (Phase 1). The results from ZAQ will be compared to the clinical diagnoses from interdisciplinary teams at specialised psychiatric clinics. After this initial testing phase, the ZAQ will be validated in an independent sample (Phase 2). Conclusions: The aim of the study is to investigate the discriminative properties (ASD vs. SD), diagnostic accuracy, and validity of the schiZotypy Autism Questionnaire (ZAQ). Funding: Funding was provided by Psychiatric Centre Glostrup, Copenhagen Denmark, Sofiefonden (Grant number: FID4107425), Trygfonden (Grant number:153588), Takeda Pharma. Trial registration: Clinical Trials, NCT05213286, Registered 28 January 2022, clinicaltrials.gov/ct2/show/NCT05213286?cond = RAADS&draw = 2&rank = 1. [ABSTRACT FROM AUTHOR]

Background: Cerebral palsy (CP) is a non-progressive disorder of movement and posture due to a static insult to the brain. In CP, the depth of investigation is guided by the patients' medical history and their clinical examination. Magnetic resonance imaging (MRI) has a high yield and is widely used for investigation in CP. Case presentation: In this paper, we report a novel DDX3X variant in a girl afflicted with the X-linked mental retardation-102 (MRX102). The girl had been misdiagnosed with CP in her early life based on a comprehensive clinical evaluation and associated clinical features, such as developmental delay, reduced activities of the arms and legs, and abnormal brain MRI. Subsequently, whole-exome sequencing was applied to better distinguish between CP and actual MRX102 with similar characteristics. Conclusions: We report on a de novo heterozygous DDX3X variant mimicking cerebral palsy and suggest a thorough and conscientious review during diagnosis of CP. [ABSTRACT FROM AUTHOR]

To mitigate the use of antibiotics for many of the multifactorial diseases seen in pigs, horses and cattle, new diagnostic tools are needed. Acute phase protein (APP) measurements can, in humans, be used to guide antibiotic treatment initiation, evaluate treatment efficacy, and make a prognosis. The aim of this review is to collect evidence on the clinical functionality of APP measurements as a tool to guide antibiotic treatment in pigs, horses, and cattle. Literature was retrieved using Medline, CAB Abstracts and Google Scholar. The acute phase response has been investigated for a plethora of diseases and clinical signs and the major acute phase proteins are elevated in diseased compared to healthy animals. Few studies correlated acute phase response with aetiology, antibiotic treatment efficacy, prognosis, or severity of disease. The existing research does not support that APP can be used to guide antibiotic treatment, but the reported studies indicate that C-reactive protein (CRP) might be able to differentiate between bacterial and non-bacterial causes of disease in pigs. Serum amyloid A (SAA) might reflect underlying aetiology in horses and infectious or non-infectious cases of mastitis in cows. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic, low parasite density malaria infections are difficult to detect with currently available point-of-care diagnostics. This study piloted a loop-mediated isothermal amplification (LAMP) kit for field-friendly, high-throughput detection of asymptomatic malaria infections during mass screening and treatment (MSAT) in Zanzibar, a malaria pre-elimination setting. Methods: Screening took place in three known hotspot areas prior to the short rains in November. Finger-prick blood was taken for screening by rapid diagnostic test (RDT) and LAMP and collected on filter paper for subsequent polymerase chain reaction (PCR) analyses. LAMP results were compared to RDT and to PCR using McNemar's test. Results: Approximately 1,000 people were screened. RDT detected ten infections (1.0% (95% CI 0.3-1.6)) whilst both LAMP and PCR detected 18 (1.8% (95% CI 0.9-2.6)) infections. However, PCR identified three infections that LAMP did not detect and vice versa. LAMP testing was easy to scale-up in field conditions requiring minimal training and equipment, with results ready one to three hours after screening. Conclusions: Despite lower than expected prevalence, LAMP detected a higher number of infections than the currently used diagnostic, RDT. LAMP is a field-friendly, sensitive diagnostic test that could be useful for MSAT malaria campaigns which require quick results to enable prompt treatment. [ABSTRACT FROM AUTHOR]

Background: Fetal alcohol spectrum disorders (FASD) is an umbrella term covering several conditions for which alcohol consumption during pregnancy is taken to play a causal role. The benefit of individuals being identified with a condition within FASD remains controversial. The objective of the present study was to identify ethical aspects and consequences of diagnostics, interventions, and family support in relation to FASD.Methods: Ethical aspects relating to diagnostics, interventions, and family support regarding FASD were compiled and discussed, drawing on a series of discussions with experts in the field, published literature, and medical ethicists.Results: Several advantages and disadvantages in regards of obtaining a diagnosis or description of the condition were identified. For instance, it provides an explanation and potential preparedness for not yet encountered difficulties, which may play an essential role in acquiring much needed help and support from health care, school, and the social services. There are no interventions specifically evaluated for FASD conditions, but training programs and family support for conditions with symptoms overlapping with FASD, e.g. ADHD, autism, and intellectual disability, are likely to be relevant. Stigmatization, blame, and guilt are potential downsides. There might also be unfortunate prioritization if individuals with equal needs are treated differently depending on whether or not they meet the criteria for a specific condition.Conclusions: The value for the concerned individuals of obtaining a FASD-related description of their condition - for instance, in terms of wellbeing - is not established. Nor is it established that allocating resources based on whether individuals fulfil FASD-related criteria is justified, compared to allocations directed to the most prominent specific needs. [ABSTRACT FROM AUTHOR]

Background: Malaria in pregnancy remains a major public health problem in the globe, especially in sub-Saharan Africa. In malaria endemic areas, most pregnant women remain asymptomatic, but malaria could still cause complications on the mother and her offspring; as well as serve as reservoirs to transmit infection. Despite these effects, no attention is given to the diagnosis of asymptomatic Plasmodium infections (APIs) using highly sensitive and specific laboratory diagnostic tools in Ethiopia. Therefore, the goal of this study was to compare the performance of Rapid Diagnostic Test (RDT), microscopy and real-time polymerase chain reaction (RT-PCR) to detect APIs among pregnant women. Methods: A health facility based cross -sectional study was conducted among pregnant women attending antenatal care at Fendeka town health facilities Jawi district, northwest Ethiopia from February to March, 2019. A total of 166 participants were enrolled by using convenient sampling technique. Socio-demographic features were collected using a semi structured questionnaire. Dried blood spot (DBS) samples were collected for molecular analysis. Asymptomatic Plasmodium infection on pregnant women was diagnosed using RDT, microscopy and RT-PCR. Descriptive statistics were used to determine the prevalence of APIs. Method comparison was performed, and Cohen's kappa coefficient (k) was used to determine the degree of agreement among the diagnostic methods. Parasite densities were also calculated. Results: The prevalence of API was 9.6%, 11.4% and 18.7% using RDT, microscopy and RT-PCR, respectively. The overall proportion of API was 19.3%. Sensitivity of the RDT was 83.3% as compared with microscopy. Rapid Diagnostic Test and microscopy also showed sensitivity of 50% and 60%, respectively, as compared with RT-PCR. The mean parasite density was 3213 parasites/µl for P falciparum and 1140 parasites/µl of blood for P. vivax. Conclusion: Prevalence of API in the study area was high. Both RDT and microscopy had lower sensitivity when compared with RT-PCR. Therefore, routine laboratory diagnosis of API among pregnant women should be given attention and done with better sensitive and specific laboratory diagnostic tools. [ABSTRACT FROM AUTHOR]

Background: Several interventions have been put in place to promote access to quality malaria case management services in Uganda's private sector, where most people seek treatment. This paper describes evidence using a mixedmethod approach to examine the role, readiness and performance of private providers at a national level in Uganda. These data will be useful to inform strategies and policies for improving malaria case management in the private sector. Methods: The ACTwatch national anti-malarial outlet survey was conducted concurrently with a fever case management study. The ACTwatch nationally representative anti-malarial outlet survey was conducted in Uganda between May 18th 2015 and July 2nd 2015. A representative sample of sub-counties was selected in 14 urban and 13 rural clusters with probability proportional to size and a census approach was used to identify outlets. Outlets eligible for the survey met at least one of three criteria: (1) one or more anti-malarials were in stock on the day of the survey; (2) one or more anti-malarials were in stock in the 3 months preceding the survey; and/or (3) malaria blood testing (microscopy or RDT) was available. The fever case management study included observations of provider-patient interactions and patient exit interviews. Data were collected between May 20th and August 3rd, 2015. The fever case management study was implemented in the private sector. Potential outlets were identified during the main outlet survey and included in this sub-sample if they had both artemisinin-based combination therapy (ACT) [artemether- lumefantrine (AL)], in stock on the day of survey as well as diagnostic testing available. Results: A total of 9438 outlets were screened for eligibility in the ACTwatch outlet survey and 4328 outlets were found to be stocking anti-malarials and were interviewed. A total of 9330 patients were screened for the fever case management study and 1273 had a complete patient observation and exit interview. Results from the outlet survey illustrate that the majority of anti-malarials were distributed through the private sector (54.3%), with 31.4% of all anti-malarials distributed through drug stores and 14.4% through private for-profit health facilities. Availability of different anti-malarials and diagnostic testing in the private sector was: ACT (80.7%), quality-assured (QA) ACT (72.0%), sulfadoxine-pyrimethamine (SP) (47.1%), quinine (73.2%) and any malaria blood testing (32.9%). Adult QAACT ($1.62) was three times more expensive than SP ($0.48). The results from the fever case management study found 44.4% of respondents received a malaria test, and among those who tested positive for malaria, 60.0% received an ACT, 48.5% received QAACT; 14.4% a non-artemisinin therapy; 14.9% artemether injection, and 42.5% received an antibiotic. Conclusion: The private sector plays an important role in malaria case management in Uganda. While several private sector initiatives have improved availability of QAACT, there are gaps in malaria diagnosis and distribution of non-artemisinin monotherapies persists. Further private sector strategies, including those focusing on drug stores, are needed to increase coverage of parasitological testing and removal of non-artemisinin therapies from the marketplace. [ABSTRACT FROM AUTHOR]

Background: Malaria continues to be a serious public health problem particularly in Africa. Many people infected with malaria do not access effective treatment due to high price. At the same time many individuals receiving malaria drugs do not suffer from malaria because of the common practice of presumptive diagnosis. A global subsidy on artemisinin-based combination therapy (ACT) has recently been suggested to increase access to the most effective malaria treatment. Methods: Following the recommendation by World Health Organization that parasitological testing should be performed before treatment and ACT prescribed to confirmed cases only, it is investigated in this paper if a subsidy on malaria rapid diagnostic tests (RDTs) should be incorporated. A model is developed consisting of a representative individual with fever suspected to be malaria, seeking care at a specialized drug shop where RDTs, ACT medicines, and cheap, less effective anti-malarials are sold. Assuming that the individual has certain beliefs of the accuracy of the RDT and the probability that the fever is malaria, the model predicts the diagnosis-treatment behaviour of the individual. Subsidies on RDTs and ACT are introduced to incentivize appropriate behaviour: choose an RDT before treatment and purchase ACT only if the test is positive. Results: Solving the model numerically suggests that a combined subsidy on both RDT and ACT is cost minimizing and improves diagnosis-treatment behaviour of individuals. For certain beliefs, such as low trust in RDT accuracy and strong belief that a fever is malaria, subsidization is not sufficient to incentivize appropriate behaviour. Conclusions: A combined subsidy on both RDT and ACT rather than a single subsidy is likely required to improve diagnosis-treatment behaviour among individuals seeking care for malaria in the private sector. [ABSTRACT FROM AUTHOR]

Background: Variation in laboratory healthcare data due to seasonal changes is a widely accepted phenomenon. Seasonal variation is generally not systematically accounted for in healthcare settings. This study applies a newly developed adjustment method for seasonal variation to analyze the effect seasonality has on machine learning model classification of diagnoses. Methods: Machine learning methods were trained and tested on ~ 22 million unique records from ~ 575,000 unique patients admitted to Danish hospitals. Four machine learning models (adaBoost, decision tree, neural net, and random forest) classifying 35 diseases of the circulatory system (ICD-10 diagnosis codes, chapter IX) were run before and after seasonal adjustment of 23 laboratory reference intervals (RIs). The effect of the adjustment was benchmarked via its contribution to machine learning models trained using hyperparameter optimization and assessed quantitatively using performance metrics (AUROC and AUPRC). Results: Seasonally adjusted RIs significantly improved cardiovascular disease classification in 24 of the 35 tested cases when using neural net models. Features with the highest average feature importance (via SHAP explainability) across all disease models were sex, C- reactive protein, and estimated glomerular filtration. Classification of diseases of the vessels, such as thrombotic diseases and other atherosclerotic diseases consistently improved after seasonal adjustment. Conclusions: As data volumes increase and data-driven methods are becoming more advanced, it is essential to improve data quality at the pre-processing level. This study presents a method that makes it feasible to introduce seasonally adjusted RIs into the clinical research space in any disease domain. Seasonally adjusted RIs generally improve diagnoses classification and thus, ought to be considered and adjusted for in clinical decision support methods. [ABSTRACT FROM AUTHOR]

Background: Household surveys are important tools for monitoring the malaria disease burden and measuring impact of malaria control interventions with parasite prevalence as the primary metric. However, estimates of parasite prevalence are dependent on a number of factors including the method used to detect parasites, age of the population sampled, and level of immunity. To better understand the influence of diagnostics, age, and endemicity on estimates of parasite prevalence and how these change over time, community-based surveys were performed for two consecutive years in three settings and the sensitivities of microscopy and immunochromatographic rapid diagnostic tests (RDTs) were assessed, considering polymerase chain reaction (PCR) as the gold standard. Methods: Surveys were conducted over the same two-month period in 2012 and 2013 in each of three sub-counties in Uganda: Nagongera in Tororo District (January-February), Walukuba in Jinja District (March-April), and Kihihi in Kanungu District (May-June). In each sub-county, 200 households were randomly enrolled and a household questionnaire capturing information on demographics, use of malaria prevention methods, and proxy indicators of wealth was administered to the head of the household. Finger-prick blood samples were obtained for RDTs, measurement of hemoglobin, thick and thin blood smears, and to store samples on filter paper. Results: A total of 1200 households were surveyed and 4433 participants were included in the analysis. Compared to PCR, the sensitivity of microscopy was low (65.3 % in Nagongera, 49.6 % in Walukuba and 40.9 % in Kihihi) and decreased with increasing age. The specificity of microscopy was over 98 % at all sites and did not vary with age or year. Relative differences in parasite prevalence across different age groups, study sites, and years were similar for microscopy and PCR. The sensitivity of RDTs was similar across the three sites (range 77.2-82.8 %), was consistently higher than microscopy (p < 0.001 for all pairwise comparisons), and decreased with increasing age. The specificity of RDTs was lower than microscopy (76.3 % in Nagongera, 86.3 % in Walukuba, and 83.5 % in Kihihi) and varied significantly by year and age. Relative differences in parasite prevalence across age groups and study years differed for RDTs compared to microscopy and PCR. Conclusion: Malaria prevalence estimates varied with diagnostic test, age, and transmission intensity. It is important to consider the effects of these parameters when designing and interpreting community-based surveys. [ABSTRACT FROM AUTHOR]

Background: Malaria is the single largest cause of illness in Uganda. Since the year 2008, the Global Fund has rolled out several funding streams for malaria control in Uganda. Among these are mechanisms aimed at increasing the availability and affordability of artemisinin-based combination therapy (ACT). This paper examines the availability and affordability of first-line malaria treatment and diagnostics in the private sector, which is the preferred first point of contact for 61% of households in Uganda between 2007 and 2018. Methods: Cross-sectional surveys were conducted between 2007 and 2018, based on a standardized World Health Organization/Health Action International (WHO/HAI) methodology adapted to assess availability, patient prices, and affordability of ACT medicines in private retail outlets. A minimum of 30 outlets were surveyed per year as prescribed by the standardized methodology co-developed by the WHO and Health Action International. Availability, patient prices, and affordability of malaria rapid diagnostic tests (RDTs) was also tracked from 2012 following the rollout of the test and treat policy in 2010. The median patient prices for the artemisinin-based combinations and RDTs was calculated in US dollars (USD). Affordability was assessed by computing the number of days' wages the lowest-paid government worker (LPGW) had to pay to purchase a treatment course for acute malaria. Results: Availability of artemether/lumefantrine (A/L), the first-line ACT medicine, increased from 85 to100% in the private sector facilities during the study period. However, there was low availability of diagnostic tests in private sector facilities ranging between 13% (2012) and 37% (2018). There was a large reduction in patient prices for an adult treatment course of A/L from USD 8.8 in 2007 to USD 1.1 in 2018, while the price of diagnostics remained mostly stagnant at USD 0.5. The affordability of ACT medicines and RDTs was below one day's wages for LPGW. Conclusions: Availability of ACT medicines in the private sector medicines retail outlets increased to 100% while the availability of diagnostics remained low. Although malaria treatment was affordable, the price of diagnostics remained stagnant and increased the cumulative cost of malaria management. Malaria stakeholders should consolidate the gains made and consider the inclusion of diagnostic kits in the subsidy programme. [ABSTRACT FROM AUTHOR]

Background: Malaria is receding in many endemic countries with intervention scale -up against the disease. However, this resilient scourge may persist in low-grade submicroscopic infections among semi-immune members of the population, and be poised for possible resurgence, creating challenges for detection and assessment of intervention impact. Parasite genotyping methods, such as the molecular barcode, can identify specific malaria parasite types being transmitted and allow tracking and evaluation of parasite population structure changes as interventions are applied. This current study demonstrates application of pre-amplification methods for successful detection and genotyping of residual Plasmodium falciparum infections during a dramatic malarial decline. Methods: The study was a prospective cross-sectional design and based on a 2,000 sq km vicinity of Macha Mission Hospital in southern Zambia. Willing and predominantly asymptomatic residents of all ages were screened for malaria by microscopy during the 2005 and 2008 transmission seasons, with simultaneous collection of dried blood spots (DBS) on filter paper, and extraction of Plasmodium falciparum DNA was performed. Plasmodium falciparum infections were genotyped using a 24 SNP-based molecular barcode assay using real-time PCR. Submicroscopic parasitaemia samples were subjected to pre-amplification using TaqMan PreAmp Master Mix following the manufacturer's instructions before SNP barcode analysis. Results: There was a dramatic decline of malaria between 2005 and 2008, and the geometric mean parasite density (95% CI) fell from 704/μL (390-1,271) in 2005 to 39/μL (23-68) in 2008, culminating in a large proportion of submicroscopic infections of which 90% failed to yield ample DNA for standard molecular characterization among 2008 samples. Pre-amplification enabled successful detection and genotyping of 74% of these low-grade reservoir infections, overall, compared to 54% that were detectable before pre-amplification (p <0.0005, n = 84). Furthermore, nine samples negative for parasites by microscopy and standard quantitative PCR amplification were positive after pre-amplification. Conclusions: Pre-amplification allows analysis of an otherwise undetectable parasite population and may be instrumental for parasites identification, tracking and assessing the impact of interventions on parasite populations during malaria control and elimination programmes when parasitaemia is expected to decline to submicroscopic levels. [ABSTRACT FROM AUTHOR]

Background: Malaria diagnosis has received renewed interest in recent years, associated with the increasing accessibility of accurate diagnosis through the introduction of rapid diagnostic tests and new World Health Organization guidelines recommending parasite-based diagnosis prior to anti-malarial therapy. However, light microscopy, established over 100 years ago and frequently considered the reference standard for clinical diagnosis, has been neglected in control programmes and in the malaria literature and evidence suggests field standards are commonly poor. Microscopy remains the most accessible method for parasite quantitation, for drug efficacy monitoring, and as a reference of assessing other diagnostic tools. This mismatch between quality and need highlights the importance of the establishment of reliable standards and procedures for assessing and assuring quality. This paper describes the development, function and impact of a multi-country microscopy external quality assurance network set up for this purpose in Asia. Methods: Surveys were used for key informants and past participants for feedback on the quality assurance programme. Competency scores for each country from 14 participating countries were compiled for analyses using paired sample t-tests. In-depth interviews were conducted with key informants including the programme facilitators and national level microscopists. Results: External assessments and limited retraining through a formalized programme based on a reference slide bank has demonstrated an increase in standards of competence of senior microscopists over a relatively short period of time, at a potentially sustainable cost. The network involved in the programme now exceeds 14 countries in the Asia-Pacific, and the methods are extended to other regions. Conclusions: While the impact on national programmes varies, it has translated in some instances into a strengthening of national microscopy standards and offers a possibility both for supporting revival of national microcopy programmes, and for the development of globally recognized standards of competency needed both for patient management and field research. [ABSTRACT FROM AUTHOR]

Background: Patients with rare diseases usually go through years of diagnostic odysseys. The large number of rare diseases and the associated lack of expertise pose a major challenge to physicians. There are few physicians dealing with patients with rare diseases and they usually work in a limited number of specialized centers. The aim of this study was to evaluate the diagnostic efficiency of an expert center. Methods: The diagnostic pathway of 78 patients of the outpatient clinic for rare inflammatory systemic diseases with renal involvement was analyzed retrospectively. For this purpose, each examination day was documented with the corresponding examinations performed from the onset of initial symptoms. Three time points were considered: The time when patients first visited a physician with symptoms, the time when patients consulted an expert, and the time when they received the correct diagnosis. In addition, it was documented whether the diagnosis could be made without the expert, or only with the help of the expert. The examinations that confirmed the diagnosis were also documented for each patient. Results: A correct diagnosis was made without the help of the expert in only 21% of cases. Each patient visited an average of 6 physicians before consulting the expert. Targeted diagnostics enabled the expert to make the correct diagnosis with an average of seven visits, or one inpatient stay. However, referral to the expert took an average of 4 years. Conclusion: The data show that rapid and targeted diagnostics were possible in the expert center due to the available expertise and the interdisciplinary exchange. Early diagnosis is of great importance for many patients, as an early and correct therapy can be decisive for the course of the disease. [ABSTRACT FROM AUTHOR]

Background: To explore the distinguishing diagnostic value and clinical application potential of deep neural networks (DNN) for pathological images of thyroid tumors. Methods: A total of 799 pathological thyroid images of 559 patients with thyroid tumors were retrospectively analyzed. The pathological types included papillary thyroid carcinoma (PTC), medullary thyroid carcinoma (MTC), follicular thyroid carcinoma (FTC), adenomatous goiter, adenoma, and normal thyroid gland. The dataset was divided into a training set and a test set. Resnet50, Resnext50, EfficientNet, and Densenet121 were trained using the training set data and tested with the test set data to determine the diagnostic efficiency of different pathology types and to further analyze the causes of misdiagnosis. Results: The recall, precision, negative predictive value (NPV), accuracy, specificity, and F1 scores of the four models ranged from 33.33% to 100.00%. The area under curve (AUC) ranged from 0.822 to 0.994, and the Kappa coefficient ranged from 0.7508 to 0.7713. However, the performance of diagnosing FTC, adenoma, and adenomatous goiter was slightly inferior to other types of pathological tissues. Conclusion: The DNN model achieved satisfactory results in the task of classifying thyroid tumors by learning thyroid pathology images. These results indicate the potential of the DNN model for the efficient diagnosis of thyroid tumor histopathology. [ABSTRACT FROM AUTHOR]

Background: On admission to hospital, patients with community-acquired pneumonia (CAP), undergo extensive diagnostic testing. Two high-throughput laboratory-based PCR panels which return a result in 5.5 hours (h) have been developed to test for pathogens commonly associated with upper (Respiratory 1 Panel) and lower (Respiratory 3 Panel) respiratory tract infections (GeneFirst, Oxford). These could replace multiple diagnostic tests currently used. Methods: An online survey, completed by senior clinicians in the UK, France and Spain, was used to collect data on the diagnostic testing of immunocompetent and immunocompromised adults admitted to hospital with CAP, including the cost of diagnostics. Data were used to inform a cost-comparison model. For each country, the average cost of diagnostic testing per patient was calculated separately for immunocompetent and immunocompromised patients. The model compared three testing strategies with standard of care (SoC). In the Panel 1 strategy, the Respiratory 1 Panel was used for patients that would otherwise have tests which could be replaced by Respiratory 1 Panel, equivalent strategies for Respiratory 3 Panel and for both panels combined were assessed. Results: In total, 48 surveys were completed (UK = 17; France = 15; Spain = 16). Compared with SoC, the Panel 1 + 3 strategy was most favourable, resulting in cost savings for immunocompetent and immunocompromised patients respectively, of €22.09 (£18.50) and €26.12 (£21.88) in the UK, €99.60 and €108.77 in France and €27.07 and €51.87 in Spain. Conclusion: In all three countries, the use of these respiratory panels could reduce the average cost of diagnostics used for patients admitted to hospital with CAP. [ABSTRACT FROM AUTHOR]