Development Of Diagnostic Algorithms Research Articles

Profile of Thrombin Generation Assay and Thromboelastometry in Women with Moderate and Severe Preeclampsia. the Roadmap-Preeclampsia Study

Introduction: Preeclampsia is a frequent vascular complication of pregnancy and figures among the major causes of maternal and neonatal morbidity and mortality. Early diagnosis and prompt, targeted treatment remain a unmet need. Hypercoagulability and endothelial cell activation are among the principal pathogenetic mechanisms in patients with preeclempsia. Development of diagnostic algorithms including clinically relevant biomarkers of hypercoagulability is expect to improve the management of preeclampsia. Among the numerous coagulation test, Global Coagulation Assays (GCA) such as thrombogram and thromboelastometry, could be of potential value for the evaluation of blood hypercoagulability. They provide information, on thrombin generation process, clot formation kinetics, clot firmness and even fibrinolysis potential. Aim: In this study we investigated the clinical accuracy of whole blood thromboelastometry (ROTEM®), and thrombin generation assay (calibrated automated thrombography: CAT® assay) to identify women with preeclampsia and we tried to compare their sensitivity. Methods: An observational retrospective case-control study was conducted. Plasma samples were collected from 84 women divided into three groups, the healthy pregnant (HP) group (n=35), the mild preeclampsia (MP) group (n=34) and the severe preeclampsia (SP) group (n=15). Thromboelastometry in whole blood was performed on ROTEM delta instrument (Tem Innovations GmbH, Werfen, Munich, Germany) with INTEM reagent. Thrombin generation triggered by PPP reagent low® (1 pM TF and 4µM phospholipid) was measured in platelet poor plasma. Thrombogram was also assessed in the presence or absence of thrombomodulin and the corresponding ration was calculated. Blood was collected at the diagnosis of preeclampsia (groups MP and SP) or at the equivalent months of pregnancy in the control group (HP). Statistical analysis was performed using the PASW Statistics 17.0.2 (SPSS Inc.) for Windows. Results: Thromboelastometry analysis showed that the clotting time (CT) was significantly longer in SP group as compared to MP and HP group. Both preeclampsia groups had longer clot formation time (CFT as compared to HP-group. MP-group had longer CFT as compared to SP-group. The α angle was significantly lower in SP-group as compared to the HP and MP groups. The maximum clot firmness was significantly higher in MP groups as compared to either HP or SP-group. The mean lysis (ML) was lower in both preeclampsia groups as compared to the HP group (Table 1). Thrombogram analysis showed that the lag-time of thrombin generation was significantly longer in both MP and SP groups as compared to HP group. Moreover, SP group showed significantly longer lag -time as compared to MP-group. Peak and the endogenous thrombin potential (ETP) were significantly higher in MP group as compared to either HP or SP groups. The mean rate index of the propagation phase of thrombin generation was not significantly different among the three groups whereas the thrombomodulin ratio for the ETP was significantly shorter in the SP-group (Table 2). Both tests showed a significant prolongation of the initiation phase of blood coagulation (reflected on CT and lag-time) in SP. The levels of clotting factors and fibrinogen were normal in all patients and none was on anticoagulant treatment. Thus, this prolongation reflects changes at the levels of TFPI and Thrmbomodulin reflecting an endothelial cell activation. ROTEM showed a decrease of the α-angle and MCF in SP group which is related with a lower platelet count in these patients. ROTEM showed enhanced fibrinolysis in both MP and SP groups Women with MP showed higher Peak and ETP than SP, MP showed higher ratio of ETP (TM+/TM-) than SP. Conclusion: The two GCA proved complementary information on the status of blood coagulation in pregnant women with preeclampsia. ROTEM provides information on clot formation kinetics and clot firmness as well as on fibrinolysis activation, which allow to differentiate SP from HP. However, the capacity of the assay for identification of patients with MP is limited. Thrombin generation assay showed a distinct profile between the three groups, which allowed differentiating the MP from HP as well as from SP. Disclosures No relevant conflicts of interest to declare.

Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease due to mutations in UMOD and MUC1

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an increasingly recognized cause of end-stage kidney disease, primarily due to mutations in UMOD and MUC1. The lack of clinical recognition and the small size of cohorts have slowed the understanding of disease ontology and development of diagnostic algorithms. We analyzed two registries from Europe and the United States to define genetic and clinical characteristics of ADTKD-UMOD and ADTKD-MUC1 and develop a practical score to guide genetic testing. Our study encompassed 726 patients from 585 families with a presumptive diagnosis of ADTKD along with clinical, biochemical, genetic and radiologic data. Collectively, 106 different UMOD mutations were detected in 216/562 (38.4%) of families with ADTKD (303 patients), and 4 different MUC1 mutations in 72/205 (35.1%) of the families that are UMOD-negative (83 patients). The median kidney survival was significantly shorter in patients with ADTKD-MUC1 compared to ADTKD-UMOD (46 vs. 54 years, respectively), whereas the median gout-free survival was dramatically reduced in patients with ADTKD-UMOD compared to ADTKD-MUC1 (30 vs. 67 years, respectively). In contrast to patients with ADTKD-UMOD, patients with ADTKD-MUC1 had normal urinary excretion of uromodulin and distribution of uromodulin in tubular cells. A diagnostic algorithm based on a simple score coupled with urinary uromodulin measurements separated patients with ADTKD-UMOD from those with ADTKD-MUC1 with a sensitivity of 94.1%, a specificity of 74.3% and a positive predictive value of 84.2% for a UMOD mutation. Thus, ADTKD-UMOD is more frequently diagnosed than ADTKD-MUC1, ADTKD subtypes present with distinct clinical features, and a simple score coupled with urine uromodulin measurements may help prioritizing genetic testing.

Epigenetics of suicidal behavior

Suicide is the second leading cause of death among young people and therefore being a serious global problem worldwide. The study of genetic and epigenetic factors in the development of suicidal behavior plays an important role in the development of advanced methods of diagnosis and treatment of this pathology. The role of hereditary factors in the development of suicidal behavior is estimated at 30–55 %, with a pronounced comorbidity with other psychopathologies. The study of genetic liability to suicidal behavior is based on molecular-genetic methods including association and linkage analyses, chip gene expression arrays, and genome-wide association studies. Published data identified multiple genes including those involved in the functioning of serotonergic (SLC6A4, TPH, 5-HT1A), hypothalamic-pituitary-adrenal systems (FKBP5) and polyamines (SAT and OATL1) associated with suicidal behavior. However, the diversity of interacting genetic loci complicates the interpretation of the development of a complex phenotype of pathology and prevents the association from being detected. To solve this problem and interpret the missing relationship between the environment and the genome, promising results were obtained from a study of epigenetic factors, which affected the expression of a number of candidate genes involved in brain functioning in suicidal behavior. The analysis of a brain obtained from suicide victims, representing a unique tool for the analysis of modified genomic processes, revealed a wide range of reprogramming patterns of DNA methylation in promoters of the genes of polyamine (OAZ1, OAZ2, AMD1, ARG2, SKA2), serotonergic (SLC6A4) and GABAergic (GABRA1) systems, HPA-axis (GR, NR3C1), tyrosine kinase (TrkB) receptors, brain-derived neurotrophic factor (BDNF). The role of histone modifications in distinct genes (Cx30, Cx43, TrkB.T1) and the expression of specific long noncoding RNAs and microRNAs in the development of suicidal behavior, which is promising for the development of diagnostic algorithms and target therapy, is discussed.

Lumbosacral pain in athletes and ballet dancers: spondylolysis and spondylolisthesis

Purpose of research. Development of diagnostic algorithm for lumbosacral pain syndrome (PCBS) caused by spondylolysis and spondylolisthesis of III degree in athletes and ballet dancers. Material and methods. 212 patients athletes and entertainers of BA - summer with PCBS caused by spondylolysis (171 persons) and spondylolisthesis of III degree (41 persons) of lumbar vertebrae were under observation. Clinical and neurological, x-ray studies, ultrasonography, computed tomography, scintigraphy, as well as the study of markers of bone tissue re - sorption (calcium in urine) and bone formation (alkaline phosphatase) were carried out. Results. Clinical manifestations spondylolysis malespecific (pain after exercise); with the progression of instability and incipient spondylolisthesis pain, strengthening - esja at sharp movements, increased muscle tone of extensors of the back and the rear muscle groups of the thigh. Decisive in the diagnosis are radiological methods. Information content of standard spondylograms is 84.6%), functional-96.7%. To clarify the localization, the size of the arc defect, as well as in subsequent control examinations, an additional study is carried out in 3/4 projections (information content of 99.2%). A highly sensitive informative method is scintigraphy, which allows to determine the presence of bone tissue rearrangement in the first days after the injury. The focus of hyperfixation, or Vice versa, hypothically radiopharmaceutical characteristics would constitute an increase or decrease of metabolic processes. With the help of scintigraphy, you can track the dynamics of reparative processes and determine the timing of the resumption of professional activities. Ultrasonography also helps to detect instability in the vertebral segment in the early stages of its development and monitor the dynamics in the treatment process. Detection of osteopenia evidence of a violation of bone metabolism, which must be considered in the treatment-be sure to use drugs that affect bone metabolism and calcium homeostasis. Conclusion. The combination of standard, functional radiographs, as well as x-rays in oblique projections and scintigraphy is quite adequate for the diagnosis of splondylolysis, spondylolisthesis and the detection of instability in athletes and ballet dancers.

Evidence from Consultation Defines the Difference Between Clinical Doctorates and the Ph.D. in Clinical Laboratory Science

Since the inception of the doctorate in clinical laboratory science (DCLS), universities sponsoring educational programs for this new practitioner have struggled with its academic placement. The PhD is considered the highest achievement level and oriented toward research. Practice doctorates are considered applied though still at the doctoral level and classified as terminal degrees for many healthcare professions. Rutgers University, the first to offer the DCLS, opted to launch the educational program for this new practitioner as an advanced practice clinical doctorate, conceiving the practice to be applied and patient/consumer focused. During completion of the first DCLS curriculum, evidence emerged describing an additional curriculum need to augment competencies in clinical research equivalent to competencies associated with the Ph.D. During the DCLS residency year, the Consultation Model was implemented in four clinical settings: Consumer Information (CI), a national consultation network; Diagnostic Management Intervention (DMI), laboratory consultation; Patient Care Intervention (PCI)**, clinical service consultation; and Utilization Review (UR), EHR and LIS review consultation. Data were collected on multiple variables: provider type, diagnosis, diagnostic question, testing cycle phase, treatment phase, and complexity (hand-offs and/or logic steps). Analyses of the consultation variables indicated the need for additional clinical research competencies, particularly data analytics associated with data warehouses built from EHR/LIS elements, and development of diagnostic algorithms supporting treatment paths. Adding these additional research competencies to the DCLS curriculum is underway which will result in a dual degree option, DCLS/Ph.D. Doctoral students will be accepted into either program but must demonstrate aptitude in clinical research to progress to the Ph.D.

RNA sequencing and swarm intelligence-enhanced classification algorithm development for blood-based disease diagnostics using spliced blood platelet RNA.

Blood-based diagnostics tests, using individual or panels of biomarkers, may revolutionize disease diagnostics and enable minimally invasive therapy monitoring. However, selection of the most relevant biomarkers from liquid biosources remains an immense challenge. We recently presented the thromboSeq pipeline, which enables RNA sequencing and cancer classification via self-learning and swarm intelligence-enhanced bioinformatics algorithms using blood platelet RNA. Here, we provide the wet-lab protocol for the generation of platelet RNA-sequencing libraries and the dry-lab protocol for the development of swarm intelligence-enhanced machine-learning-based classification algorithms. The wet-lab protocol includes platelet RNA isolation, mRNA amplification, and preparation for next-generation sequencing. The dry-lab protocol describes the automated FASTQ file pre-processing to quantified gene counts, quality controls, data normalization and correction, and swarm intelligence-enhanced support vector machine (SVM) algorithm development. This protocol enables platelet RNA profiling from 500 pg of platelet RNA and allows automated and optimized biomarker panel selection. The wet-lab protocol can be performed in 5 d before sequencing, and the algorithm development can be completed in 2 d, depending on computational resources. The protocol requires basic molecular biology skills and a basic understanding of Linux and R. In all, with this protocol, we aim to enable the scientific community to test platelet RNA for diagnostic algorithm development.

Current view on phenotypic and genetic features of autosomal recessive inherited peripheral neuropathies

Inherited peripheral neuropathies (IPNs) are a heterogeneous group of hereditary motor and sensory neuropathies (HMSN), hereditary motor neuropathies, and hereditary sensory neuropathies. IPNs can be inherited in autosomal dominant, autosomal recessive or X-linked manner. In clinical practice, isolated cases are more common, and the absence of genealogical data significantly complicates differential diagnosis. About 45% of HMSN cases lack genetic confirmation. For a number of autosomal recessive IPNs, peculiar clinical, electrophysiological and histological features can be distinguished, however, recent publications show IPNs often to have pronounced clinical and genetic heterogeneity. That complicates the differential diagnosis of hereditary neuropathies. Prevalence of autosomal recessive pathology increases in remote populations and isolates due to a local founder effects. As the literature review showed, there are many such examples among autosomal recessive IPNs. Detection of the founder effect and major mutations in the population and development of diagnostic algorithms based on these data can significantly improve the diagnostic process.

Sniffing out resistance – Rapid identification of urinary tract infection-causing bacteria and their antibiotic susceptibility using volatile metabolite profiles

Antibiotic resistance is set to be an unprecedented threat to modern medicine. ‘Sniffing’ bacteria potentially offers a rapid way to determine susceptibility. A successful proof-of-principle study is described, using thermal desorption-gas chromatography-mass spectrometry (TDGCMS) to ‘smell’ cephalexin and ciprofloxacin resistant and sensitive Urinary Tract Infection (UTI)-causing bacteria. 578 peaks at unique retention times were detected from 86 chromatograms of 18 bacterial isolates (E. coli, K. pneumoniae and P. aeruginosa). The isolates were grown with and without the presence of antibiotic. Chi-square analysis found 9 compounds that differed significantly between cephalexin sensitive and resistant isolates, and 22 compounds that differed significantly between ciprofloxacin sensitive and resistant isolates, at p ≤ 0.05. When antibiotic was added to the media, more differences were found in the cephalexin group, attributed to lysis, but not in the ciprofloxacin group. Further work with large sample sizes will potentially enable the development of diagnostic algorithms using presence/absence of particular compounds of interest.

Clinical observation of severe laryngomalacia an infant

Relevance. Disorders of the larynx are a poorly studied section of pediatric otorhinolaryngology. In recent years, the incidence of congenital malformations of the larynx increases, and laryngomalacia is the most common. Diagnosis of this disease is difficult in the conditions of outpatient department without necessary equipment. However, each doctor should understand the importance of diagnosis of laryngomalacia, because this disease can get a severe form with a potential injury to the life and health of the child, especially during the catarrhal disease.
 Objectives: development of diagnostic algorithm and the choice of optimal treatment strategy, intended to restoring of laryngeal functions.
 Materials and methods. Your attention is the case of severe clinical course laringomalacia an infant and its surgical correction in the clinic of Otorhinolaryngology, St. Petersburg State Pediatric Medical University. The child was observed by the standard method: flexible laryngoscopy, x-ray examination of the neck in the lateral view, x-ray examination of the chest, laboratory blood tests.
 Results. This article demonstrates the diagnostic algorithm and the choice of optimal treatment strategy, which avoids the imposition of tracheostomy and rehabilitation the child in infancy. A multidisciplinary approach to the treatment of children with laringomalacia is validated.
 Conclusions. This clinical case is a striking example of the need for early diagnosis of the type of congenital malformation of the larynx in newborns with congenital stridor and other signs of dysfunction of the larynx.

Finite element modelling and validation for breast cancer detection using digital image elasto-tomography.

Finite element (FE) models are increasingly used to validate experimental data in breast cancer. This research constructed a biomechanical FE model for breast shaped phantoms used to develop and validate a mechanical vibration based screening system. Such models do not currently exist but would enhance development of this screening technology. Three phantoms were modelled: healthy, with 10 and 20mm inclusions. The overall goal was to create models with enough accuracy to replace experimental phantoms in providing data to optimize diagnostic algorithms for digital image-based elasto-tomography (DIET) screening technologies. FE model results were validating against experimental DIET phantom data for over 4000 collected points on each model and phantom using cross-correlation coefficients between experimental simulated data and direct comparison. Results showed good to strong correlation ranging from 0.7 to 1.0 in all cases with over 90% having a value over 0.9. Magnitudes for each frame of the dynamic response also matched well, indicating that the material properties and geometry were accurate enough to provide this level of correlation. These results justify the use of FE model generated data for in silico diagnostic algorithm development testing. The overall modelling and validation approach is not overly complex, and thus generalizable to similar problems using mechanical properties of silicone phantoms, and might be extensible to human cases with further work. Graphical abstract Validate that dynamic displacements show that the model can be used in place of phantoms for rapid development of diagnostic algorithms that use surface motion to detect underlying mechanical properties.

The clinical diagnostic aspects of acute pancreatic encephalopathy

The pancreatic encephalopathy is characterized by various focal neurological symptomatic and sporadic fast development of dementia is considered as a rare complication of acute pancreatitis developing in 9-35% of patients with diseases of pancreas. Factually every patient with acute pancreatitis has a risk of development of pancreatic encephalopathy that significantly makes severer course of disease and increases lethality. The review article considers particular aspects of clinical manifestations and probable diagnostic algorithm of neurological disorders observed in patients with acute pancreatitis. The actuality of development of diagnostic algorithm of pancreatic encephalopathy is emphasized. This algorithm will permit ultimately early, probably at pre-clinical stage, discover the mentioned complication of acute pancreatitis with the purpose of not only ultimate early detection of pancreatic encephalopathy but also development of pathogenically conditioned therapeutic algorithm considering all chains of pathogenesis.

The epidemiological and pathogenic aspects of acute pancreatic encephalopathy

The article considers particular aspects of epidemiology and pathogenesis of neurological disorders detected in patients with acute pancreatitis. The pancreatic encephalopathy characterizing by various focal neurological symptomatic and sometimes rapid development of dementia is considered as a rare complication of acute pancreatitis developing in 9-35% of patients with diseases of pancreas. Factually, every patient with acute pancreatitis has a risk of development of pancreatic encephalopathy which significantly increases graveness of course and lethality of disease. Therefore, the emphasis is made on development of diagnostic algorithm under pancreatic encephalopathy permitting discovering this complication of acute pancreatitis at as much as possible early even possibly at pre-clinical stage. The comprehensive investigation of pathogenesis of pancreatic encephalopathy with the purpose of elaboration of pathogenetically conditioned therapeutic algorithm considering all parts of pathogenesis.

The Diagnostic Algorithm Patients Examination with Penile Deformation

Objective: The article outlines informational content of the methods used for treatment and diagnostic algorithm development for patients with different types of penile deformations. Materials and Methods: For last 10 years there 189 patients with penile deviations were examined and treated. For diagnostic we used questionnaires, US with Doppler, MRI and CT. According to erectile function, presence of inflammation in plaque methods of treatment (surgical or conservative) was chose. Results: Positive results were observed in 94% of patients after Nesbit operations (corporoplication) and in 82% of patients after corporoplastic. Effectiveness conservative treatment was about 70%. Conclusions: Pre-surgery examination of patients with penile curvature and any type of deformation must comprise ultrasound and pharmacodopplerography along with the medical history and physical examination. In controversial clinical cases in order to prove or discard possible inflammatory peri-process it is necessary to conduct MRI.

OPTIMIZATION OF DIAGNOSTIC IMAGING IN BREAST CANCER

The paper presents the results of breast imaging for 47200 women. Breast cancer was detected in 862 (1.9%) patients, fibroadenoma in 1267 (2.7%) patients and isolated breast cysts in 1162 (2.4%) patients. Different types of fibrocystic breast disease (adenosis, diffuse fibrocystic changes, local fibrosis and others) were observed in 60.1% of women. Problems of breast cancer visualization during mammography, characterized by the appearance of fibrocystic mastopathy (sclerosing adenosis, fibrous bands along the ducts) have been analyzed. Data on the development of diagnostic algorithms including the modern techniques for ultrasound and interventional radiology aimed at detecting early breast cancer have been presented.

Structured interview for mild traumatic brain injury after military blast: inter-rater agreement and development of diagnostic algorithm.

The existing gold standard for diagnosing a suspected previous mild traumatic brain injury (mTBI) is clinical interview. But it is prone to bias, especially for parsing the physical versus psychological effects of traumatic combat events, and its inter-rater reliability is unknown. Several standardized TBI interview instruments have been developed for research use but have similar limitations. Therefore, we developed the Virginia Commonwealth University (VCU) retrospective concussion diagnostic interview, blast version (VCU rCDI-B), and undertook this cross-sectional study aiming to 1) measure agreement among clinicians' mTBI diagnosis ratings, 2) using clinician consensus develop a fully structured diagnostic algorithm, and 3) assess accuracy of this algorithm in a separate sample. Two samples (n = 66; n = 37) of individuals within 2 years of experiencing blast effects during military deployment underwent semistructured interview regarding their worst blast experience. Five highly trained TBI physicians independently reviewed and interpreted the interview content and gave blinded ratings of whether or not the experience was probably an mTBI. Paired inter-rater reliability was extremely variable, with kappa ranging from 0.194 to 0.825. In sample 1, the physician consensus prevalence of probable mTBI was 84%. Using these diagnosis ratings, an algorithm was developed and refined from the fully structured portion of the VCU rCDI-B. The final algorithm considered certain symptom patterns more specific for mTBI than others. For example, an isolated symptom of "saw stars" was deemed sufficient to indicate mTBI, whereas an isolated symptom of "dazed" was not. The accuracy of this algorithm, when applied against the actual physician consensus in sample 2, was almost perfect (correctly classified = 97%; Cohen's kappa = 0.91). In conclusion, we found that highly trained clinicians often disagree on historical blast-related mTBI determinations. A fully structured interview algorithm was developed from their consensus diagnosis that may serve to enhance diagnostic standardization for clinical research in this population.

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia.

Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P<0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P=0.002; odds ratio 8.43, 95% confidence interval 2.24-31.76). Multinomial logistic regression analysis identified peripheral neuropathy, family history and hearing loss as significant predictors of the genotype, and the same three variables showed the highest performance in genotype classification in a decision tree analysis. Of these variables, peripheral neuropathy had the highest specificity (91%), negative predictive value (83%) and positive likelihood ratio (5.87) for the diagnosis of a nuclear DNA defect. These results indicate that peripheral neuropathy is a rare finding in patients with single mitochondrial DNA deletions but that it is highly predictive of an underlying nuclear DNA defect. This observation may facilitate the development of diagnostic algorithms. We suggest that nuclear gene testing may enable a more rapid diagnosis and avoid muscle biopsy in patients with progressive external ophthalmoplegia and peripheral neuropathy.

Structured Interview for Mild TBI After Military Blast: Interrater Agreement and Development of Diagnostic Algorithm

1) Measure agreement among clinicians’ mild Traumatic Brain Injury (TBI) diagnosis ratings, 2) using clinician consensus develop a fully structured diagnostic algorithm, and 3) assess accuracy of this algorithm in a separate sample.

Hypersensitivity to antibiotics in patients with cystic fibrosis

Hypersensitivity reactions to parenterally administered antibiotics (HRPA) are a substantial problem in managing CF. We conducted this observational study to assess their nature and frequency as well as risk factors. By reviewing medical records and conducting interviews, age, sex, FEV1, ∆F508-genotype, pseudomonal colonisation, allergy history, antibiotic exposure and HRPA were recorded. Of 100 patients included in the study, 60 had ≥1 HRPA. Overall, 3205 antibiotic courses with 185 HRPA were ascertained. Changes in therapy followed 65% of HRPA. Eighty-four percent of severe HRPA occurred during days 1-4. Approximately 10% of treatment courses with cefepime and piperacillin/tazobactam caused HRPA. Years of pseudomonal colonisation and cumulative annual exposure were significant risk factors. During days 1-4 of antibiotic treatment patients are at elevated risk for HRPA. HRPA are drug-specific and dependent on cumulative annual exposure. Elucidation of HRPA's immunological mechanisms and development of diagnostic algorithms for clinical use are required.

Protocolo diagnóstico de las taquicardias de QRS ancho

Ventricular tachycardia is the commonest underlying mechanism for wide QRS tachycardia, representing between 80% to even 95% of patients with ischemic heart disease. Accurate differentiation of ventricular tachycardia from supraventricular tachycardia with aberrant conduction or preexcitation syndromes and pacemaker mediated supraventricular tachycardias, holds important implications in terms of prognosis and dysrhythmia management. Haemodynamic tolerance should not be considered diagnostic criterion. Careful study of the electrocardiogram during sinus rhythm and tachycardia provides diagnostic clue. Different diagnostic algorithms have been published, but their use is complicated and may lead to misdiagnosis. We believe it is essential to understand the criteria for the development of diagnostic algorithms rather than merely its application. When in doubt, common sense should prevail and ventricular tachycardia should be considered the default diagnosis in wide-QRS-complex tachycardias

Integrated diagnostics: proceedings from the 9th biennial symposium of the International Society for Strategic Studies in Radiology

The International Society for Strategic Studies in Radiology held its 9th biennial meeting in August 2011. The focus of the programme was integrated diagnostics and massive computing. Participants discussed the opportunities, challenges, and consequences for the discipline of radiology that will likely arise from the integration of diagnostic technologies. Diagnostic technologies are increasing in scope, including advanced imaging techniques, new molecular imaging agents, and sophisticated point-of-use devices. Advanced information technology (IT), which is increasingly influencing the practice of medicine, will aid clinical communication and the development of “population images” that represent the phenotype of particular diseases, which will aid the development of diagnostic algorithms. Integrated diagnostics offer increased operational efficiency and benefits to patients through quicker and more accurate diagnoses. As physicians with the most expertise in IT, radiologists are well placed to take the lead in introducing IT solutions and cloud computing to promote integrated diagnostics. To achieve this, radiologists must adapt to include quantitative data on biomarkers in their reports. Radiologists must also increase their role as participating physicians, collaborating with other medical specialties, not only to avoid being sidelined by other specialties but also to better prepare as leaders in the selection and sequence of diagnostic procedures. Key Points • New diagnostic technologies are yielding unprecedented amounts of diagnostic information.• Advanced IT/cloud computing will aid integration and analysis of diagnostic data.• Better diagnostic algorithms will lead to faster diagnosis and more rapid treatment.