OBJECTIVE: In the Czech Republic, over 97% of all pregnant women undergo some type of antenatal screening for Down's syndrome. In about 95% of cases with a confirmed fetal chromosomal abnormality, the pregnancy is terminated. The most commonly used test is the first trimester combined test. We investigated the impact of implementing an integrated sequential test to improve the detection of Down's syndrome pregnancies. METHODS: Data on the incidence of congenital defects, number of births, and affected pregnancies terminated are recorded in the National Registry of Congenital Anomalies. Anonymous data on cases of Down's syndrome diagnosed antenatally or postnatally between 2010 and 2015 in one of the large antenatal care centers were analyzed. RESULTS: There were 600 diagnoses of Down's syndrome (5.7 per 1000 births), 90% of which were made antenatally. Of antenatally detected cases, 80% were indicated for diagnostic procedure by multimarker screening results. In the multimarker screen positive group, 75% cases were first trimester positive and 25% second trimester positive (most of these had positive integrated test results). Among Down's syndrome cases indicated for antenatal diagnosis by multimarker screening results 6.25% (n = 26) were first trimester negative, and became positive after integration with the second trimester screening results. CONCLUSIONS: Results from five major Czech antenatal centers confirm that an integrated sequential test would detect 80-85% of Down's syndrome fetuses in the first trimester and at least an extra 5-10% of Down's syndrome pregnancies in the second trimester of pregnancy. These are important data that should be considered in implementing the national antenatal screening program.

• Keywords
• Antenatal screening, Down’s syndrome, integrated test,
• MeSH
• Algorithms MeSH
• Cell-Free System MeSH
• Adult MeSH
• Down Syndrome diagnosis   MeSH
• Pregnancy Trimester, Second MeSH
• False Positive Reactions MeSH
• Humans MeSH
• Chorionic Gonadotropin, beta Subunit, Human blood   MeSH
• Nuchal Translucency Measurement MeSH
• Peptide Fragments blood   MeSH
• Mass Screening methods   MeSH
• Prenatal Diagnosis methods   MeSH
• Pregnancy Trimester, First MeSH
• Registries MeSH
• Decision Making MeSH
• Pregnancy-Associated Plasma Protein-A metabolism   MeSH
• Pregnancy MeSH
• Ultrasonography, Prenatal MeSH
• Maternal Age MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Chorionic Gonadotropin, beta Subunit, Human MeSH
• PAPPA protein, human MeSH Browser
• Peptide Fragments MeSH
• Pregnancy-Associated Plasma Protein-A MeSH
• urinary gonadotropin fragment MeSH Browser

OBJECTIVE: The aim of this comprehensive paper is to acquaint the readers with evaluation of the retinal images using the arteficial intelligence (AI). Main focus of the paper is diabetic retinophaty (DR) screening. The basic principles of the artificial intelligence and algorithms that are already used in clinical practice or are shortly before approval will be described. METHODOLOGY: Describing the basic characteristics and mechanisms of different approaches to the use of AI and subsequently literary minireview clarifying the current state of knowledge in the area. RESULTS: Modern systems for screening diabetic retinopathy using deep neural networks achieve a sensitivity and specificity of over 80 % in most published studies. The results of specific studies vary depending on the definition of the gold standard, number of images tested and on the evaluated parameters. CONCLUSION: Evaluation of images using AI will speed up and streamline the diagnosis of DR. The use of AI will allow to keep the quality of the eye care at least on the same level despite the raising number of the patients with diabetes.

• Keywords
• Diabetic retinopathy, artificial intelligence, diabetic retinopathy, mass screening, screening,
• MeSH
• Algorithms MeSH
• Diabetes Mellitus * MeSH
• Diabetic Retinopathy * diagnosis   MeSH
• Intelligence MeSH
• Humans MeSH
• Mass Screening MeSH
• Artificial Intelligence MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

AIM: The aim of this study was to develop an algorithm to prompt early clinical suspicion of mucopolysaccharidosis type I (MPS I). METHODS: An international working group was established in 2016 that comprised 11 experts in paediatrics, rare diseases and inherited metabolic diseases. They reviewed real-world clinical cases, selected key signs or symptoms based on their prevalence and specificity and reached consensus about the algorithm. The algorithm was retrospectively tested. RESULTS: An algorithm was developed. In patients under two years of age, kyphosis or gibbus deformity were the key symptoms that raised clinical suspicion of MPS I and in those over two years they were kyphosis or gibbus deformity, or joint stiffness or contractures without inflammation. The algorithm was tested on 35 cases, comprising 16 Hurler, 10 Hurler-Scheie, and nine Scheie patients. Of these 35 cases, 32 (91%) - 16 Hurler, nine Hurler-Scheie and seven Scheie patients - would have been referred earlier if the algorithm had been used. CONCLUSION: The expert panel developed and tested an algorithm that helps raise clinical suspicion of MPS I and would lead to a more prompt final diagnosis and allow earlier treatment.

• Keywords
• Algorithm, Diagnosis, Kyphosis, Mucopolysaccharidosis, Symptoms,
• MeSH
• Algorithms * MeSH
• Early Diagnosis * MeSH
• Child MeSH
• Risk Assessment MeSH
• Internationality MeSH
• Consensus MeSH
• Humans MeSH
• Mucopolysaccharidosis I diagnosis   therapy   MeSH
• Multimorbidity MeSH
• Infant, Newborn MeSH
• Neonatal Screening methods   MeSH
• Child, Preschool MeSH
• Prognosis MeSH
• Disease Progression MeSH
• Retrospective Studies MeSH
• Sex Factors MeSH
• Severity of Illness Index MeSH
• Age Factors MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The aim of this paper is to review the diagnostics of congenital disorders of glycosylation (CDG), an ever expanding group of diseases. Development delay, neurological, and other clinical abnormalities as well as various non-specific laboratory changes can lead to the first suspicion of the disease. Still common screening test for most CDG types, including CDG Ia, is isoelectric focusing/polyacrylamide gel electrophoresis (IEF). IEF demonstrates the hypoglycosylation of various glycoproteins, usually serum transferrin. Other methods, such as agarose electrophoresis, capillary electrophoresis, high-performance liquid chromatography, micro-column separation combined with turbidimetry, enzyme-(EIA) and radioimmunoassay (RIA) have also been used for screening. However, these methods do not recognize all CDG defects, so other approaches including analysis of membrane-linked markers and urine oligosaccharides should be taken. Confirmation of diagnosis and detailed CDG subtyping starts with thorough structure analysis of the affected lipid-linked oligosaccharide or protein-(peptide)-linked-glycan using metabolic labeling and various (possibly mass-spectrometry combined) techniques. Decreased enzyme activity in peripheral leukocytes/cultured fibroblasts or analysis of affected transporters and other functional proteins combined with identification of specific gene mutations confirm the diagnosis. Prenatal diagnosis, based on enzyme assay or mutation analysis, is also available. Peri-/post-mortem investigations of fatal cases are important for genetic counseling. Evaluation of various analytical approaches and proposed algorithms for investigation complete the review.

• MeSH
• Algorithms MeSH
• Biomarkers MeSH
• Glycosylation MeSH
• Humans MeSH
• Mass Screening * MeSH
• Carbohydrate Metabolism, Inborn Errors diagnosis   genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Biomarkers MeSH

BACKGROUND: Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications. OBJECTIVES: We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity). METHODS: We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses. RESULTS: Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81. CONCLUSIONS: The algorithm is a useful predictive tool and could be integrated into dystonia routine diagnostic protocols. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

• Keywords
• diagnostic yield, dystonia, exome sequencing, prediction, rare disease, scoring algorithm,
• MeSH
• Algorithms MeSH
• Dystonic Disorders * genetics   MeSH
• Dystonia * diagnosis   genetics   MeSH
• Genetic Testing MeSH
• Humans MeSH
• Parkinson Disease * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

OBJECTIVES: Refeeding syndrome (RFS) can be a life-threatening metabolic condition after nutritional replenishment if not recognized early and treated adequately. There is a lack of evidence-based treatment and monitoring algorithm for daily clinical practice. The aim of the study was to propose an expert consensus guideline for RFS for the medical inpatient (not including anorexic patients) regarding risk factors, diagnostic criteria, and preventive and therapeutic measures based on a previous systematic literature search. METHODS: Based on a recent qualitative systematic review on the topic, we developed clinically relevant recommendations as well as a treatment and monitoring algorithm for the clinical management of inpatients regarding RFS. With international experts, these recommendations were discussed and agreement with the recommendation was rated. RESULTS: Upon hospital admission, we recommend the use of specific screening criteria (i.e., low body mass index, large unintentional weight loss, little or no nutritional intake, history of alcohol or drug abuse) for risk assessment regarding the occurrence of RFS. According to the patient's individual risk for RFS, a careful start of nutritional therapy with a stepwise increase in energy and fluids goals and supplementation of electrolyte and vitamins, as well as close clinical monitoring, is recommended. We also propose criteria for the diagnosis of imminent and manifest RFS with practical treatment recommendations with adoption of the nutritional therapy. CONCLUSION: Based on the available evidence, we developed a practical algorithm for risk assessment, treatment, and monitoring of RFS in medical inpatients. In daily routine clinical care, this may help to optimize and standardize the management of this vulnerable patient population. We encourage future quality studies to further refine these recommendations.

• Keywords
• Hypophosphatemia, Nutritional therapy, Refeeding syndrome, Treatment recommendation,
• MeSH
• Algorithms * MeSH
• Risk Assessment standards   MeSH
• Nutrition Assessment * MeSH
• Inpatients MeSH
• Consensus MeSH
• Evidence-Based Practice standards   MeSH
• Humans MeSH
• Decision Support Techniques * MeSH
• Mass Screening standards   MeSH
• Refeeding Syndrome diagnosis   prevention & control   MeSH
• Risk Factors MeSH
• Practice Guidelines as Topic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

PURPOSE: Genetic testing in consanguineous families advances the general comprehension of pathophysiological pathways. However, short stature (SS) genetics remain unexplored in a defined consanguineous cohort. This study examines a unique pediatric cohort from Sulaimani, Iraq, aiming to inspire a genetic testing algorithm for similar populations. METHODS: Among 280 SS referrals from 2018-2020, 64 children met inclusion criteria (from consanguineous families; height ≤ -2.25 SD), 51 provided informed consent (30 females; 31 syndromic SS) and underwent investigation, primarily via exome sequencing. Prioritized variants were evaluated by the American College of Medical Genetics and Genomics standards. A comparative analysis was conducted by juxtaposing our findings against published gene panels for SS. RESULTS: A genetic cause of SS was elucidated in 31 of 51 (61%) participants. Pathogenic variants were found in genes involved in the GH-IGF-1 axis (GHR and SOX3), thyroid axis (TSHR), growth plate (CTSK, COL1A2, COL10A1, DYM, FN1, LTBP3, MMP13, NPR2, and SHOX), signal transduction (PTPN11), DNA/RNA replication (DNAJC21, GZF1, and LIG4), cytoskeletal structure (CCDC8, FLNA, and PCNT), transmembrane transport (SLC34A3 and SLC7A7), enzyme coding (CYP27B1, GALNS, and GNPTG), and ciliogenesis (CFAP410). Two additional participants had Silver-Russell syndrome and 1 had del22q.11.21. Syndromic SS was predictive in identifying a monogenic condition. Using a gene panel would yield positive results in only 10% to 33% of cases. CONCLUSION: A tailored testing strategy is essential to increase diagnostic yield in children with SS from consanguineous populations.

• Keywords
• Consanguinity, Genetic testing algorithm, Pediatric endocrinology, Short stature, Short stature genes,
• MeSH
• Algorithms MeSH
• Child MeSH
• Genetic Testing * methods   MeSH
• Humans MeSH
• Adolescent MeSH
• Dwarfism * genetics   epidemiology   diagnosis   MeSH
• Consanguinity MeSH
• Child, Preschool MeSH
• Pedigree MeSH
• Exome Sequencing MeSH
• Body Height genetics   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Iraq epidemiology   MeSH

An algorithm of evaluation of diagnostic data for electronic screening of subclinical and clinical mastitis was derived from 5848 field measurements of the electric conductivity of mammary gland secretions and from the same number of clinical, bacteriological and cytological examinations of 92 dairy cows. The algorithm consists in the calculation of arithmetical mean of the two highest values of mixed, i.e. absolute, and or differential conductivity of a seven-day sliding cycle. Regardless of the intensity of disease forms, for healthy and colonized mammary glands, for mammary glands suffering from nonspecific subclinical mastitis, infectious subclinical mastitis and infectious clinical mastitis, the overall agreement with findings according to repeated clinical, bacteriological and cytological examinations made 88.8% with 4.2% of falsely negative and 7.0% of falsely positive findings. The overall agreement for persistent forms of diseases made 95.3% without falsely negative findings and with 4.7% of falsely positive findings.

• MeSH
• Electric Conductivity MeSH
• Mastitis, Bovine diagnosis   MeSH
• Milk * MeSH
• Cattle MeSH
• Animals MeSH
• Check Tag
• Cattle MeSH
• Animals MeSH
• Publication type
• English Abstract MeSH
• Journal Article MeSH

PURPOSE: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations. METHODS: Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8). Markers and decision limits were converted to multiples of the median (MoM) to allow comparison between centres. RESULTS: NBS programmes, algorithms and decision limits varied considerably. Only nine centres used the recommended second-tier marker total homocysteine (tHcy). The median decision limits of all centres were ≥ 2.35 for high and ≤ 0.44 MoM for low methionine, ≥ 1.95 for high and ≤ 0.47 MoM for low methionine/phenylalanine, ≥ 2.54 for high propionylcarnitine and ≥ 2.78 MoM for propionylcarnitine/acetylcarnitine. These decision limits alone had a 100%, 100%, 86% and 84% sensitivity for the detection of CBSD, MATI/IIID, iRMD and cRMD, respectively, but failed to detect six individuals with cRMD. To enhance sensitivity and decrease second-tier testing costs, we further adapted these decision limits using the data of 15 000 healthy newborns. CONCLUSIONS: Due to the favorable outcome of early treated patients, NBS for homocystinurias is recommended. To improve NBS, decision limits should be revised considering the population median. Relevant markers should be combined; use of the postanalytical tools offered by the CLIR project (Collaborative Laboratory Integrated Reports, which considers, for example, birth weight and gestational age) is recommended. tHcy and methylmalonic acid should be implemented as second-tier markers.

• MeSH
• Acetylcarnitine metabolism   MeSH
• Phenylalanine metabolism   MeSH
• Glycine N-Methyltransferase deficiency   metabolism   MeSH
• Homocysteine metabolism   MeSH
• Homocystinuria diagnosis   metabolism   MeSH
• Carnitine analogs & derivatives   metabolism   MeSH
• Methylmalonic Acid metabolism   MeSH
• Humans MeSH
• Methionine metabolism   MeSH
• Methylenetetrahydrofolate Reductase (NADPH2) deficiency   metabolism   MeSH
• Infant, Newborn MeSH
• Neonatal Screening methods   MeSH
• Psychotic Disorders diagnosis   metabolism   MeSH
• Muscle Spasticity diagnosis   metabolism   MeSH
• Amino Acid Metabolism, Inborn Errors diagnosis   metabolism   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Acetylcarnitine MeSH
• Phenylalanine MeSH
• Glycine N-Methyltransferase MeSH
• Homocysteine MeSH
• Carnitine MeSH
• Methylmalonic Acid MeSH
• Methionine MeSH
• Methylenetetrahydrofolate Reductase (NADPH2) MeSH
• propionylcarnitine MeSH Browser

AIM: Frail older people typically suffer several chronic diseases, receive multiple medications and are more likely to be institutionalized in residential aged care facilities. In such patients, optimizing prescribing and avoiding use of high-risk medications might prevent adverse events. The present study aimed to develop a pragmatic, easily applied algorithm for medication review to help clinicians identify and discontinue potentially inappropriate high-risk medications. METHODS: The literature was searched for robust evidence of the association of adverse effects related to potentially inappropriate medications in older patients to identify high-risk medications. Prior research into the cessation of potentially inappropriate medications in older patients in different settings was synthesized into a four-step algorithm for incorporation into clinical assessment protocols for patients, particularly those in residential aged care facilities. RESULTS: The algorithm comprises several steps leading to individualized prescribing recommendations: (i) identify a high-risk medication; (ii) ascertain the current indications for the medication and assess their validity; (iii) assess if the drug is providing ongoing symptomatic benefit; and (iv) consider withdrawing, altering or continuing medications. Decision support resources were developed to complement the algorithm in ensuring a systematic and patient-centered approach to medication discontinuation. These include a comprehensive list of high-risk medications and the reasons for inappropriateness, lists of alternative treatments, and suggested medication withdrawal protocols. CONCLUSIONS: The algorithm captures a range of different clinical scenarios in relation to potentially inappropriate medications, and offers an evidence-based approach to identifying and, if appropriate, discontinuing such medications. Studies are required to evaluate algorithm effects on prescribing decisions and patient outcomes. Geriatr Gerontol Int 2016; 16: 1002-1013.

• Keywords
• algorithm, high-risk medications, medication review, medication withdrawal, residential aged care facilities,
• MeSH
• Algorithms * MeSH
• Patient Safety MeSH
• Chronic Disease drug therapy   MeSH
• Risk Assessment MeSH
• Frail Elderly statistics & numerical data   MeSH
• Humans MeSH
• Inappropriate Prescribing prevention & control   statistics & numerical data   MeSH
• Drug-Related Side Effects and Adverse Reactions epidemiology   prevention & control   MeSH
• Polypharmacy * MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Potentially Inappropriate Medication List statistics & numerical data   MeSH
• Age Factors MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Review MeSH