scholarly journals Beyond the average patient: how neuroimaging models can address heterogeneity in dementia

Brain ◽  
2021 ◽  
Author(s):  
Serena Verdi ◽  
Andre F Marquand ◽  
Jonathan M Schott ◽  
James H Cole
Keyword(s):  
Clinical Presentation ◽  
Diagnostic Group ◽  
Data Driven ◽  
Control Treatment ◽  
Onset Age ◽  
Group Homogeneity ◽  
Average Patient ◽  
Dementia Research ◽  
Treatment Responses ◽  
Statistical Designs

Abstract Dementia is a highly heterogeneous condition, with pronounced individual differences in onset age, clinical presentation, progression rates and neuropathological hallmarks, even within a specific diagnostic group. However, the most common statistical designs used in dementia research studies and clinical trials overlook this heterogeneity, instead relying on the comparison of group average differences (e.g., patient versus control, treatment versus placebo), implicitly assuming within-group homogeneity. This one-size-fits-all approach potentially limits our understanding of dementia aetiology, hindering the identification of effective treatments. Neuroimaging has enabled characterisation of the average neuroanatomical substrates of dementias; however, the increasing availability of large open neuroimaging datasets provides the opportunity to examine patterns of neuroanatomical variability in individual patients. In this Update review we outline the causes and consequences of heterogeneity in dementia and discuss recent research which aims to directly tackle heterogeneity, rather than assume that dementia affects everyone in the same way. We introduce spatial normative modelling as an emerging data-driven technique which can be applied to dementia data to model neuroanatomical variation, capturing individualised neurobiological “fingerprints”. Such methods have the potential to detect clinically relevant subtypes, track an individual’s disease progression or evaluate treatment responses, with the goal of moving towards precision medicine for dementia.

scholarly journals Shaping a data-driven era in dementia care pathway through computational neurology approaches

BMC Medicine ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
KongFatt Wong-Lin ◽  
Paula L. McClean ◽  
Niamh McCombe ◽  
Daman Kaur ◽  
Jose M. Sanchez-Bornot ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Clinical Decision Making ◽  
Care Pathway ◽  
Clinical Decision Support Systems ◽  
Clinical Decision ◽  
Dementia Care ◽  
Data Driven ◽  
Main Body ◽  
Data Infrastructure ◽  
Dementia Research

Abstract Background Dementia is caused by a variety of neurodegenerative diseases and is associated with a decline in memory and other cognitive abilities, while inflicting an enormous socioeconomic burden. The complexity of dementia and its associated comorbidities presents immense challenges for dementia research and care, particularly in clinical decision-making. Main body Despite the lack of disease-modifying therapies, there is an increasing and urgent need to make timely and accurate clinical decisions in dementia diagnosis and prognosis to allow appropriate care and treatment. However, the dementia care pathway is currently suboptimal. We propose that through computational approaches, understanding of dementia aetiology could be improved, and dementia assessments could be more standardised, objective and efficient. In particular, we suggest that these will involve appropriate data infrastructure, the use of data-driven computational neurology approaches and the development of practical clinical decision support systems. We also discuss the technical, structural, economic, political and policy-making challenges that accompany such implementations. Conclusion The data-driven era for dementia research has arrived with the potential to transform the healthcare system, creating a more efficient, transparent and personalised service for dementia.

scholarly journals The importance of early management of severe biliary infection: current concepts

2021 ◽  
Author(s):  
Mireia Amillo-Zaragueta ◽  
Esther Nve ◽  
Daniel Casanova ◽  
Pau Garro ◽  
Josep M Badia
Keyword(s):  
Clinical Presentation ◽  
Multidrug Resistant ◽  
Progressive Increase ◽  
Source Control ◽  
Control Treatment ◽  
Resistant Bacteria ◽  
Review Of The Literature ◽  
Early Management ◽  
Emergency Admissions ◽  
Intravenous Antibiotics

Background. The incidence of biliary infections is rising worldwide and has become one of the main reasons for emergency admissions. Methods. Narrative review of the literature emphasizing news concepts related to the early management of biliary diseases.  Results. The bacteriology is frequently polymicrobial, with a progressive increase of multidrug resistant bacteria. The form of presentation is variable, and the mortality rate may reach 20%. When cholecystitis or cholangitis is suspected, ultrasound is the gold standard imaging test. Depending on the severity of presentation, local resistances and risk factors for multi-resistant organisms, the most appropriate empirical antibiotic treatment must be initiated. In acute cholecystitis, cholecystectomy plays the main therapeutic role. In patients not suitable for surgery, percutaneous cholecystostomy is a valid alternative for source control. Treatment of severe cholangitis is based on the drainage of the bile duct and antibiotic therapy. Conclusions. Biliary infections are serious conditions which can lead to sepsis and death. The introduction of new internationally accepted guidelines, based on clinical presentation, laboratory tests and imaging, provides a platform for their timely diagnosis and management. Early severity assessment, initiation of intravenous antibiotics and source control are fundamental to improving morbidity and mortality.

Absence of the RNF213 p.R4810K variant may indicate a severe form of pediatric moyamoya disease in Japanese patients

2021 ◽  
pp. 1-9
Author(s):  
Shoko Hara ◽  
Maki Mukawa ◽  
Hiroyuki Akagawa ◽  
Thiparpa Thamamongood ◽  
Motoki Inaji ◽  
...  
Keyword(s):  
Moyamoya Disease ◽  
Surgical Outcomes ◽  
Clinical Presentation ◽  
Rare Variants ◽  
Disease Onset ◽  
Japanese Patients ◽  
Severe Form ◽  
Onset Age ◽  
Cerebrovascular Events ◽  
Heterozygous Variant

OBJECTIVE The authors’ objective was to investigate the influence of the RNF213 p.R4810K variant on the clinical presentation and outcomes of Japanese pediatric patients with moyamoya disease. METHODS A total of 129 Japanese patients with pediatric-onset moyamoya disease (onset age ≤ 15 years) who visited the authors’ department from 2012 to 2020 participated in this study. After RNF213 p.R4810K genotyping of each patient was performed, the relationship between genotype and clinical presentation or outcomes, including onset age, initial presentation, surgical outcomes, and subsequent cerebrovascular events, was evaluated. Patients without the p.R4810K variant were tested for RNF213 variants other than p.R4810K. The authors especially focused on the results of patients who presented with moyamoya disease at younger than 1 year of age (infantile onset). RESULTS Compared with the patients with heterozygous variants, patients without the p.R4810K variant were younger at onset (7.1 ± 3.7 vs 4.4 ± 0.9 years), and all 4 patients with infantile onset lacked the p.R4810K variant. A greater proportion of patients without the p.R4810K variant presented with infarction than patients with the heterozygous variant (24.0% vs 7.6%) and a decreased proportion presented with transient ischemic attack (36.0% vs 71.7%). No significant correlation was observed between p.R4810K genotype and clinical outcomes, including surgical outcomes and subsequent cerebrovascular events; however, a decreased proportion of patients without the p.R4810K variant had good surgical outcomes compared with that of patients with the heterozygous variant (76.5% vs 92.2%). Among the 25 patients without the p.R4810K variant, 8 rare variants other than p.R4810K were identified. Three of 4 patients with infantile onset had RNF213 variants other than p.R4810K, which had a more severe functional effect on this gene than p.R4810K. CONCLUSIONS Absence of the RNF213 p.R4810K variant may be a novel biomarker for identification of a severe form of pediatric moyamoya disease.

scholarly journals Retrospective Analysis of Checkpoint Inhibitor Therapy-Associated Cases of Bullous Pemphigoid From Six German Dermatology Centers

2021 ◽  
Vol 11 ◽  
Author(s):  
Christian D. Sadik ◽  
Ewan A. Langan ◽  
Ralf Gutzmer ◽  
Maria Isabel Fleischer ◽  
Carmen Loquai ◽  
...  
Keyword(s):  
Bullous Pemphigoid ◽  
Clinical Presentation ◽  
Checkpoint Inhibitors ◽  
Corticosteroid Treatment ◽  
Time Interval ◽  
European Guidelines ◽  
Blistering Disease ◽  
Checkpoint Inhibitor Therapy ◽  
Ci Therapy ◽  
Treatment Responses

Immune-related adverse events (irAEs) are a class-effect of checkpoint inhibitors (CIs). The development of a Bullous pemphigoid (BP)-like blistering disease, driven by autoantibodies against the hemidesmosomal protein BP180, is a potentially serious irAE whose incidence seems to be increasing. We therefore set out to characterize the clinical and (immuno)histopathological features and treatment responses of cases of BP which developed during or after CI therapy collated in six German tertiary referral centers between 2014 and 2018. We identified twelve cases of BP which emerged during and/or after CI therapy. The time interval between the initiation of CI therapy and the diagnosis of BP was 3–74 weeks (median: 23 weeks). Age at the time of diagnosis of BP varied between 62 and 80 years (median: 76 years). The clinical presentation of the patients was diverse but the severity was relatively mild when compared to that seen in most cases of spontaneous BP. Only four patients met all of the immunopathological criteria recommended in the European guidelines for the diagnosis of BP. Topical corticosteroid treatment was sufficient to achieve disease control in most patients. CI therapy could be continued in 8 out of 12 patients. In summary, our study indicates that cases of BP during or after CI therapy bear several peculiarities distinguishing them from spontaneous BP. Given the diversity of the clinical presentation of CI-induced BP the application of existing diagnostic algorithms developed for spontaneous BP can be utilized to uncover the frequency and features of CI-induced BP and to develop and optimize management algorithms.

scholarly journals Data-driven criteria to assess fear remission and phenotypic variability of extinction in rats

2018 ◽  
Vol 373 (1742) ◽  
pp. 20170035 ◽  
Author(s):  
Jason Shumake ◽  
Carolyn Jones ◽  
Allison Auchter ◽  
Marie-Hélène Monfils
Keyword(s):  
Mental Health ◽  
Individual Differences ◽  
Fear Conditioning ◽  
Phenotypic Variability ◽  
Conditioned Fear ◽  
Differential Treatment ◽  
Data Driven ◽  
Output Measure ◽  
Treatment Responses

Fear conditioning is widely employed to examine the mechanisms that underlie dysregulations of the fear system. Various manipulations are often used following fear acquisition to attenuate fear memories. In rodent studies, freezing is often the main output measure to quantify ‘fear’. Here, we developed data-driven criteria for defining a standard benchmark that indicates remission from conditioned fear and for identifying subgroups with differential treatment responses. These analyses will enable a better understanding of individual differences in treatment responding. This article is part of a discussion meeting issue ‘Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists’.

Phenomapping of subgroups in hypertensive patients using unsupervised data-driven cluster analysis: An exploratory study of the SPRINT trial

2019 ◽  
Vol 26 (16) ◽  
pp. 1693-1706 ◽  
Author(s):  
Da-ya Yang ◽  
Zhi-qiang Nie ◽  
Li-zhen Liao ◽  
Shao-zhao Zhang ◽  
Hui-min Zhou ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Antihypertensive Treatment ◽  
Cox Regression ◽  
Cardiovascular Outcomes ◽  
Data Driven ◽  
Hypertensive Patients ◽  
Increased Risk ◽  
Data Driven Approach ◽  
Treatment Responses ◽  
Cluster 2

Background Hypertensive patients are highly heterogeneous in cardiovascular prognosis and treatment responses. A better classification system with phenomapping of clinical features would be of greater value to identify patients at higher risk of developing cardiovascular outcomes and direct individual decision-making for antihypertensive treatment. Methods An unsupervised, data-driven cluster analysis was performed for all baseline variables related to cardiovascular outcomes and treatment responses in subjects from the Systolic Blood Pressure Intervention Trial (SPRINT), in order to identify distinct subgroups with maximal within-group similarities and between-group differences. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular outcomes and compare the effect of intensive antihypertensive treatment in different clusters. Results Four replicable clusters of patients were identified: cluster 1 (index hypertensives); cluster 2 (chronic kidney disease hypertensives); cluster 3 (obese hypertensives) and cluster 4 (extra risky hypertensives). In terms of prognosis, individuals in cluster 4 had the highest risk of developing primary outcomes. In terms of treatment responses, intensive antihypertensive treatment was shown to be beneficial only in cluster 4 (HR 0.73, 95% CI 0.55–0.98) and cluster 1 (HR 0.54, 95% CI 0.37–0.79) and was associated with an increased risk of severe adverse effects in cluster 2 (HR 1.18, 95% CI 1.05–1.32). Conclusion Using a data-driven approach, SPRINT subjects can be stratified into four phenotypically distinct subgroups with different profiles on cardiovascular prognoses and responses to intensive antihypertensive treatment. Of note, these results should be taken as hypothesis generating that warrant further validation in future prospective studies.

Clinical presentation and treatment responses in IgM-related AL amyloidosis

Amyloid ◽  
2015 ◽  
Vol 22 (4) ◽  
pp. 229-235 ◽  
Author(s):  
Moussa Sissoko ◽  
Vaishali Sanchorawala ◽  
David Seldin ◽  
Brian Sworder ◽  
Kenneth Angelino ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Al Amyloidosis ◽  
Treatment Responses

Analysis of nasal foreign bodies in 341 children

2019 ◽  
Vol 133 (10) ◽  
pp. 908-912
Author(s):  
Z-C Lou
Keyword(s):  
Medical Records ◽  
Foreign Bodies ◽  
Clinical Presentation ◽  
Outcome Data ◽  
Septal Perforation ◽  
Body Type ◽  
Button Battery ◽  
Average Patient ◽  
The Common ◽  
Button Batteries

AbstractObjectiveThis study aimed to analyse the common presentations and treatment outcomes in cases involving nasal foreign bodies.MethodsA retrospective study was carried out over three years, from January 2014 to December 2017. Patient biodata, clinical presentation, nasal foreign body type and management outcome data were obtained from the medical records and analysed.ResultsA total of 341 cases were analysed. The average patient age was 3.7 ± 1.2 years (range, 1–19 years).Of the nine cases involving button batteries, septal perforation was initially seen in four cases and three cases had subsequent septal perforation.ConclusionOnly button battery nasal foreign bodies were associated with increased septal perforation. Use of physiological seawater nasal spray was found to reduce the likelihood of septal perforation. Most nasal foreign bodies could be removed under local anaesthesia.

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