scholarly journals Precision physiology and rescue of brain ion channel disorders

2017 ◽  
Vol 149 (5) ◽  
pp. 533-546 ◽  
Author(s):  
Jeffrey Noebels
Keyword(s):  
Ion Channel ◽  
Clinical Utility ◽  
Clinical Decision Making ◽  
Central Nervous System Disease ◽  
Clinical Decision ◽  
Channel Structure ◽  
Clinical Severity ◽  
Developmental Relationships ◽  
System Disease ◽  
Phenotypic Spectrum

Ion channel genes, originally implicated in inherited excitability disorders of muscle and heart, have captured a major role in the molecular diagnosis of central nervous system disease. Their arrival is heralded by neurologists confounded by a broad phenotypic spectrum of early-onset epilepsy, autism, and cognitive impairment with few effective treatments. As detection of rare structural variants in channel subunit proteins becomes routine, it is apparent that primary sequence alone cannot reliably predict clinical severity or pinpoint a therapeutic solution. Future gains in the clinical utility of variants as biomarkers integral to clinical decision making and drug discovery depend on our ability to unravel complex developmental relationships bridging single ion channel structure and human physiology.

scholarly journals Clinical utility of targeted SARS-CoV-2 serology testing to aid the diagnosis and management of suspected missed, late or post-COVID-19 infection syndromes: Results from a pilot service implemented during the first pandemic wave

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249791
Author(s):  
Nicola Sweeney ◽  
Blair Merrick ◽  
Rui Pedro Galão ◽  
Suzanne Pickering ◽  
Alina Botgros ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Performance Characteristics ◽  
Direct Care ◽  
Serological Testing ◽  
Internal Validation ◽  
Assay Performance ◽  
Adults And Children ◽  
Test Probability

During the first wave of the global COVID-19 pandemic the clinical utility and indications for SARS-CoV-2 serological testing were not clearly defined. The urgency to deploy serological assays required rapid evaluation of their performance characteristics. We undertook an internal validation of a CE marked lateral flow immunoassay (LFIA) (SureScreen Diagnostics) using serum from SARS-CoV-2 RNA positive individuals and pre-pandemic samples. This was followed by the delivery of a same-day named patient SARS-CoV-2 serology service using LFIA on vetted referrals at central London teaching hospital with clinical interpretation of result provided to the direct care team. Assay performance, source and nature of referrals, feasibility and clinical utility of the service, particularly benefit in clinical decision-making, were recorded. Sensitivity and specificity of LFIA were 96.1% and 99.3% respectively. 113 tests were performed on 108 participants during three-week pilot. 44% participants (n = 48) had detectable antibodies. Three main indications were identified for serological testing; new acute presentations potentially triggered by recent COVID-19 e.g. pulmonary embolism (n = 5), potential missed diagnoses in context of a recent COVID-19 compatible illness (n = 40), and making infection control or immunosuppression management decisions in persistently SARS-CoV-2 RNA PCR positive individuals (n = 6). We demonstrate acceptable performance characteristics, feasibility and clinical utility of using a LFIA that detects anti-spike antibodies to deliver SARS-CoV-2 serology service in adults and children. Greatest benefit was seen where there is reasonable pre-test probability and results can be linked with clinical advice or intervention. Experience from this pilot can help inform practicalities and benefits of rapidly implementing new tests such as LFIAs into clinical service as the pandemic evolves.

Histomolecular Phenotypes and Outcome in Adenocarcinoma of the Ampulla of Vater

2013 ◽  
Vol 31 (10) ◽  
pp. 1348-1356 ◽  
Author(s):  
David K. Chang ◽  
Nigel B. Jamieson ◽  
Amber L. Johns ◽  
Christopher J. Scarlett ◽  
Marina Pajic ◽  
...  
Keyword(s):  
Clinical Utility ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Ampulla Of Vater ◽  
Therapeutic Strategies ◽  
Prognostic Variables ◽  
Histologic Subtype ◽  
Prognostic Group ◽  
Potential Clinical Utility ◽  
Novel Therapeutic Strategies

Purpose Individuals with adenocarcinoma of the ampulla of Vater demonstrate a broad range of outcomes, presumably because these cancers may arise from any one of the three epithelia that converge at that location. This variability poses challenges for clinical decision making and the development of novel therapeutic strategies. Patients and Methods We assessed the potential clinical utility of histomolecular phenotypes defined using a combination of histopathology and protein expression (CDX2 and MUC1) in 208 patients from three independent cohorts who underwent surgical resection for adenocarcinoma of the ampulla of Vater. Results Histologic subtype and CDX2 and MUC1 expression were significant prognostic variables. Patients with a histomolecular pancreaticobiliary phenotype (CDX2 negative, MUC1 positive) segregated into a poor prognostic group in the training (hazard ratio [HR], 3.34; 95% CI, 1.69 to 6.62; P < .001) and both validation cohorts (HR, 5.65; 95% CI, 2.77 to 11.5; P < .001 and HR, 2.78; 95% CI, 1.25 to 7.17; P = .0119) compared with histomolecular nonpancreaticobiliary carcinomas. Further stratification by lymph node (LN) status defined three clinically relevant subgroups: one, patients with histomolecular nonpancreaticobiliary (intestinal) carcinoma without LN metastases who had an excellent prognosis; two, those with histomolecular pancreaticobiliary carcinoma with LN metastases who had a poor outcome; and three, the remainder of patients (nonpancreaticobiliary, LN positive or pancreaticobiliary, LN negative) who had an intermediate outcome. Conclusion Histopathologic and molecular criteria combine to define clinically relevant histomolecular phenotypes of adenocarcinoma of the ampulla of Vater and potentially represent distinct diseases with significant implications for current therapeutic strategies, the ability to interpret past clinical trials, and future trial design.

scholarly journals Dynamic Changes of Th1 Cytokines and the Clinical Significance of the IFN-γ/TNF-α Ratio in Acute Brucellosis

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Guang Xu ◽  
Peng Zhang ◽  
Rongjing Dang ◽  
Yanfang Jiang ◽  
Feng Wang ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Clinical Decision Making ◽  
Clinical Symptoms ◽  
Clinical Decision ◽  
Serum Levels ◽  
Post Treatment ◽  
Clinical Severity ◽  
Th1 Cells ◽  
Dynamic Changes ◽  
Necrosis Factor Alpha

Background. T-helper type 1 (Th1) cells and Th1-produced cytokines play essential roles in the immune response to foreign pathogens, such as Brucella spp. The aim of this study was to evaluate the dynamic changes of Th1 cells and Th1-produced cytokines in patients with acute brucellosis and their impact on clinical decision-making. Methods. Fifty-one individuals with acute brucellosis and 17 healthy subjects were enrolled in this study. The brucellosis patients were diagnosed based on clinical symptoms, laboratory tests, and clinical examination. The levels of serum gamma-interferon (IFN-γ) and tumor necrosis factor-alpha (TNF-α), along with the percentage of Th1 cells, were determined by flow cytometry bead arrays (CBA). Results. The frequency of Th1 cells, along with the levels of IFN-γ and TNF-α, was negatively correlated with the clinical parameters. The mean serum levels of IFN-γ and TNF-α and the frequency of Th1 cells were significantly higher in the brucellosis patients in comparison with the healthy subjects (p<0.05). Besides, the cytokine levels were not significantly different between the positive and negative blood culture groups. IFN-γ levels significantly decreased from 6 months to 12 months post treatment (p<0.05). However, the IFN-γ levels remained higher than those of the healthy subjects by 12 months post treatment (p<0.05). The IFN-γ/TNF-α ratio was significantly higher in severe cases than in nonsevere cases (p<0.05). Conclusions. The IFN-γ levels secreted by Th1 cells remain significantly higher than those of healthy subjects more than 12 months after treatment with antibiotics. This finding is different from similar studies. The IFN-γ/TNF-α ratio may be a feasible parameter for assessing clinical severity, yet further longitudinal studies of the immunization and inflammatory reaction of brucellosis are needed in larger patient populations.

scholarly journals 1157. Determining the Clinical Utility of 16S rRNA in the Management of Pediatric Infections

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S670-S670
Author(s):  
Peter Paul Lim ◽  
Ankita P Desai ◽  
Sree Sarah Cherian ◽  
Sindhoosha Malay
Keyword(s):  
Decision Making ◽  
16S Rrna ◽  
Clinical Utility ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Joint Fluid ◽  
Significant Difference ◽  
Pediatric Infections ◽  
Tissue Specimens ◽  
Antimicrobial Regimen

Abstract Background Conventional culture remains the gold standard to facilitate a targeted antimicrobial regimen in the treatment of bacterial infections. However, certain pediatric infections are caused by fastidious organisms and treatment with antibiotics prior to specimen collection may hamper growth of pathogens in routine culture. The use of 16S rRNA in culture negative infections has improved identification of bacterial pathogens in select scenarios. However, the specific impact of 16S rRNA on clinical decision making, especially in pediatric infections, is not well-defined. This study aims to elucidate the utility of 16S rRNA on clinical management of pediatric infections. Methods A retrospective analysis was done on different clinical specimens which had 16S rRNA performed from August 2016 – March 2020 in our institution. Detailed chart review was performed to determine how the 16S rRNA result impacted clinical decision making. Clinical utility was defined as change in patient’s overall antimicrobial regimen, pathogen confirmation, and treatment duration. Results Seventy-four samples from 71 pediatric patients were included in the analysis: 32 (43%) were fluid specimens and 42 (57%) were tissue specimens. Significant clinical utility was identified in 30 (40.5%) of 74 clinical samples (p &lt; 0.0001). Of all specimens, pulmonary samples yielded the most clinical utility (n=9, 30%) followed equally by joint fluid (n=6, 20%) and bone (n=6, 20%). There was no significant difference in clinical utility between fluid and tissue specimens (p= 0.346). In 64 patients whose antimicrobial spectrum coverage was analyzed, patients with broad spectrum coverage was decreased from 48 to 21 and narrow spectrum coverage increased from 16 to 43 using 16S rRNA result, though not significant (p= 0.4111). Of all patients included in the analysis, the median number of antibiotics used before 16S rRNA result, 2, was significantly decreased to 1 (p &lt; 0.0001). Conclusion 16S rRNA has a significant impact in terms of decreasing number of antibiotics used in treatment of pediatric infections. Pulmonary specimens have the highest clinical utility among all samples. Additional cost benefit analysis needs to be completed to further determine clinical benefit. Disclosures All Authors: No reported disclosures

Enhancing the Clinical Utility of DriveSafe DriveAware for People with Huntington’s Disease

2020 ◽  
Vol 9 (4) ◽  
pp. 353-357
Author(s):  
Monique K. Sondhu ◽  
Fiona Fisher ◽  
Julie C. Stout
Keyword(s):  
Processing Speed ◽  
Completion Time ◽  
Clinical Utility ◽  
Screening Tool ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Driving Safety ◽  
Cognitive Screening ◽  
Cognitive Information ◽  
Completion Times

DriveSafe DriveAware (DSDA) is a cognitive screening tool assessing driving safety. Previously, we found DSDA categorised some HD participants as ‘likely to pass’ on-road assessments, despite displaying cognitive impairments in domains known to impact driving. As processing speed is affected early in HD, we examined whether DSDA completion time could provide supplementary cognitive information to support clinical decision-making. The HD group completed subtests significantly slower than controls, and completion times correlated with cognitive functions essential for driving. Considering DSDA completion time may tailor the assessment for people with HD so that it is more reflective of HD-related cognitive functioning.

scholarly journals The reliability and validity of self-reported reproductive history and obstetric morbidity amongst birth to ten mothers in Soweto

Curationis ◽  
2000 ◽  
Vol 23 (4) ◽  
Author(s):  
GTH Ellison ◽  
T De Wet ◽  
KP Matshidze ◽  
P Cooper
Keyword(s):  
Clinical Utility ◽  
Clinical Decision Making ◽  
Reliability And Validity ◽  
Clinical Decision ◽  
Reproductive History ◽  
Medical Disorders ◽  
Home Based ◽  
Self Reports ◽  
Obstetric Morbidity ◽  
Clinical Measurements

Objective: To assess whether self-reports of reproductive history and obstetric morbidity provide an accurate basis for clinical decision-making. Setting, participants and methods: Self-reports of maternal age and reproductive history, together with clinical measurements of five medical disorders, were abstracted from the obstetric notes of 517 mothers whose children were enrolled in the Birth to Ten study. These data were compared to self-reported information collected by interview during the Birth to Ten study. Findings: The reliability of self-reported age and gravidity was high (R=0.810-0.993), yet self-reports of previous miscarriages, terminations, premature- and stillbirths were only fairly reliable (Kappa=0.48-0.50). Self-reported diabetes and high blood pressure had specificities of more than 95% for glycosuria, hypertension and pre-eclampsia. However, the specificity of self-reported oedema for hypertensive disorders and the specificity of self-reported urinary tract infection for STD seropositivity were only around 65%. Conclusions: The modest reliability and limited validity of self-reported obstetric morbidity undermines the clinical utility of this information. Recommendations: These results strengthen the case for providing mothers with “Home-based Maternal Records” to facilitate access to accurate obstetric information during subsequent clinical consultations.

The clinical utility of the ICD-11 classification of personality disorders and related traits: A preliminary scoping review

2021 ◽  
pp. 000486742110256
Author(s):  
Mikaela Tracy ◽  
Nikolaos Tiliopoulos ◽  
Louise Sharpe ◽  
Bo Bach
Keyword(s):  
Clinical Utility ◽  
Clinical Decision Making ◽  
Strong Support ◽  
Diagnostic System ◽  
Clinical Decision ◽  
International Classification Of Diseases ◽  
Ease Of Use ◽  
Electronic Screening ◽  
Study Characteristics

Objectives: A diagnostic system that fails to deliver clinically useful information will not be utilized and consequently will be unable to provide valuable data for health policy and clinical decision making. Therefore, it is imperative to obtain an accurate depiction of the clinical utility of the eleventh revision of the International Classification of Diseases (ICD-11) Personality Disorder (PD) model. The current mixed-methods systematic review aimed to determine the clinical utility of the ICD-11 PD classification system. Method: An electronic screening of six databases was conducted and resulting studies were subjected to specific exclusion criteria, which elicited eight studies of interest. Study characteristics were tabulated and methodological quality was appraised. Results: Four studies offered strong support for the model’s clinical utility, three offered some support accompanied by notable limitations and one study could only offer criticisms. Conclusion: Future investigation of the ICD-11 PD classification system’s (a) communicative value between clinicians and their patients, and between clinicians and their patient’s families; (b) ease of use; and (c) feasibility in terms of practical application is required to achieve a complete understanding of its clinical utility and ultimately bring clarity to the current ambiguous findings.

Criticism of psychiatric diagnosis

2019 ◽  
pp. 89-104
Author(s):  
Ahmed Samei Huda
Keyword(s):  
Mental Health ◽  
Mental Health Professionals ◽  
Clinical Utility ◽  
Clinical Decision Making ◽  
Mental Health Problems ◽  
Medical Model ◽  
Clinical Decision ◽  
Negative Consequences ◽  
Causative Factors ◽  
Medical Diagnostic

Criticisms of psychiatric diagnostic constructs from a clinical/scientific view have been made on several points: reliability, such as how often two clinicians agree on the same diagnosis; validity, such as clear separation between diagnostic constructs or presence of objective validators; utility, such as predicting outcomes and treatment responses; implying an inaccurate conception of mental health problems as diseases that also minimizes the influence of social causative factors, high rates of co-occurrence, and association with negative consequences such as stigma. Many psychiatric diagnostic constructs lack validity but often have clinical utility. This clinical utility depends on how the clinician works therefore psychiatric diagnostic constructs are well suited to the medical model but may have little utility for other mental health professionals who work differently or for researchers testing hypotheses. Diagnostic constructs have utility for administrative purposes. The criticisms can be used to generate a set of questions to evaluate psychiatric diagnostic constructs. Psychiatric diagnostic constructs are best compared with general medical diagnostic constructs because they are used for similar purposes in clinical decision-making. A comparison will be made to see if there is no overlap, some overlap, or near total overlap between general medical and psychiatric diagnostic constructs.

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