scholarly journals Charting Brain Growth and Aging at High Spatial Precision

2021 ◽  
Author(s):  
Saige Rutherford ◽  
Charlotte Fraza ◽  
Richard Dinga ◽  
Seyed Mostafa Kia ◽  
Thomas Wolfers ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Clinical Decision ◽  
Individual Variability ◽  
Population Variation ◽  
Clinical Value ◽  
Common Reference ◽  
Neuroimaging Data ◽  
Growth And Aging ◽  
Volume Models ◽  
Subcortical Volume

Defining reference models for population variation, and the ability to study individual deviations is essential for understanding inter-individual variability and its relation to the onset and progression of medical conditions. In this work, we assembled a reference cohort of neuroimaging data from 82 sites (N=58,836; ages 2-100) and use normative modeling to characterize lifespan trajectories of cortical thickness and subcortical volume. Models are validated against a manually quality checked subset (N=24,354) and we provide an interface for transferring to new data sources. We showcase the clinical value by applying the models to a transdiagnostic psychiatric sample (N=1,985), showing they can be used to quantify variability underlying multiple disorders whilst also refining case-control inferences. These models will be augmented with additional samples and imaging modalities as they become available. This provides a common reference platform to bind results from different studies and ultimately paves the way for personalized clinical decision making.

scholarly journals Clinical value of measurable residual disease testing for assessing depth, duration, and direction of response in multiple myeloma

2020 ◽  
Vol 4 (14) ◽  
pp. 3295-3301
Author(s):  
Joaquin Martinez-Lopez ◽  
Sandy W. Wong ◽  
Nina Shah ◽  
Natasha Bahri ◽  
Kaili Zhou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Decision Making ◽  
Residual Disease ◽  
Clinical Care ◽  
Progression Free Survival ◽  
Clinical Decision ◽  
Routine Practice ◽  
Clinical Value ◽  
The Impact ◽  
Measurable Residual Disease

Abstract Few clinical studies have reported results of measurable residual disease (MRD) assessments performed as part of routine practice. Herein we present our single-institution experience assessing MRD in 234 multiple myeloma (MM) patients (newly diagnosed [NDMM = 159] and relapsed [RRMM = 75]). We describe the impact of depth, duration, and direction of response on prognosis. MRD assessments were performed by next-generation sequencing of immunoglobulin genes with a sensitivity of 10−6. Those achieving MRD negativity at 10−6, as well as 10−5, had superior median progression-free survival (PFS). In the NDMM cohort, 40% of the patients achieved MRD negativity at 10−6 and 59% at 10−5. Median PFS in the NDMM cohort was superior in those achieving MRD at 10−5 vs <10−5 (PFS: 87 months vs 32 months; P < .001). In the RRMM cohort, 36% achieved MRD negativity at 10−6 and 47% at 10−5. Median PFS was superior for the RRMM achieving MRD at 10−5 vs <10−5 (PFS: 42 months vs 17 months; P < .01). Serial MRD monitoring identified 3 categories of NDMM patients: (A) patients with ≥3 MRD 10−6 negative samples, (B) patients with detectable but continuously declining clonal numbers, and (C) patients with stable or increasing clonal number (≥1 log). PFS was superior in groups A and B vs C (median PFS not reached [NR], NR, 55 respectively; P < .001). This retrospective evaluation of MRD used as part of clinical care validates MRD as an important prognostic marker in NDMM and RRMM and supports its use as an endpoint in future clinical trials as well as for clinical decision making.

Switching and Combining Antipsychotics

CNS Spectrums ◽  
2010 ◽  
Vol 15 (S6) ◽  
pp. 8-11 ◽  
Author(s):  
Christoph U. Correll
Keyword(s):  
Decision Making ◽  
Individual Differences ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Individual Variability ◽  
The Body ◽  
Striatal Dopamine ◽  
Caloric Content ◽  
Pharmacokinetic Profiles ◽  
Positron Emission

Pharmacologic knowledge can inform clinical decision-making, particularly the dosing and switching decisions made with antipsychotics. Of relevance are the pharmacokinetic (what does the body do to the drug) and the pharmacodynamic (what does the drug do to the body) properties of antipsychotics.The goal of antipsychotic dosing is to achieve sufficient dopa-mine blockade in areas where dopamine excess can lead to psychosis, mania, or aggression. Using positron emission topography, one investigation showed that response rates were considerably higher in patients who achieved >65% striatal dopamine blockade. Conversely, striatal dopamine blockade >80% predicted the emergence of extrapyramidal symptoms (EPS) or akathisia.There is, however, considerable intra-individual variability in achieving the desired 60% to 80% striatal dopamine blockade. Such variability is likely due to inter-individual differences in the absorption, distribution, metabolism and elimination of medications. At the same time, antipsychotics themselves differ in their general pharmacokinetic profiles. For example, ziprasidone absorption is ~50% less when ingested on an empty stomach than when taken with a meal; the degree of absorption depends on the caloric content, while the fat content is not relevant.

Can we satisfactorily measure the clinical value of new oncology agents with a single summary measure?

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 6606-6606
Author(s):  
Clare Frances Jones ◽  
Giles Monnickendam ◽  
Mingshu Zhu ◽  
Jan McKendrick
Keyword(s):  
Median Survival ◽  
Clinical Benefit ◽  
Survival Benefit ◽  
Clinical Decision Making ◽  
Proportional Hazards ◽  
Survival Rates ◽  
Clinical Decision ◽  
Summary Statistics ◽  
Survival Curves ◽  
Clinical Value

6606 Background: Current value frameworks (VFs) assess clinical value primarily through using clinical trial endpoints as survival metrics (e.g., median and hazard ratio (HR)). But, if key assumptions do not hold, the interpretation of these summary statistics can become problematic and fail to adequately capture the expected benefit to a patient. This has been observed with innovative oncology treatments. As a proof of concept analysis, we reviewed how two VFs (ASCO and ESMO) dealt with cases where the assumption of proportional hazards (PH) does not hold. Methods: Oncology agents approved by the FDA since 2011 were reviewed and three agents were identified with survival profiles where the assumption of PH was found not to hold because, on visual inspection, the survival curves displayed non-standard patterns: Divergence followed by convergence – panobinostat OS in RRMM; Curves initially track together then diverge – nivolumab OS in NSCLC; Curves diverge steadily then a plateau emerged in the active treatment curve – pembrolizumab PFS in refractory melanoma. We evaluated these agents to assess which measures of clinical benefit were most valued under each VF and how the issue of non-PH influenced the outcome. Results: Clinical benefit/value scores varied: ASCO: 14-27 (maximum 100), ESMO: grade 1-3. The ASCO VF uses a hierarchical approach (incorporating HR and median survival benefit, always prioritising the former) adding a bonus for survival benefit in the tail of the distribution. The combination of HR, median survival benefit 2 and 3 year survival rates in the ESMO non-curative VF can potentially capture aspects of clinical benefit in some cases of non-PH. Overall, the ASCO VF appears less flexible to accommodate non-PH than the ESMO VF. Conclusions: Despite VFs using summary statistics which cannot be easily interpreted under conditions of non-PH, the case of non-PH is not explicitly catered for. Additionally, both VFs may miss important interpretation where value is differentiated across patients groups with different response profiles which may underlie non-standard survival curves. In these situations, a more flexible approach to assessing clinical value may render VFs more relevant for clinical decision making.

Understanding engagement and potential impact of an electronic drug repository: A mixed-methods study. (Preprint)

2021 ◽  
Author(s):  
Charlene Soobiah ◽  
Michelle Phung ◽  
Mina Tadrous ◽  
Trevor Jamieson ◽  
R. Sacha Bhatia ◽  
...  
Keyword(s):  
Online Survey ◽  
Clinical Decision Making ◽  
Point Of Care ◽  
Digital Health ◽  
Inappropriate Prescribing ◽  
Clinical Decision ◽  
Qualitative Description ◽  
Structured Interviews ◽  
Clinical Value ◽  
Secondary Information

BACKGROUND Centralized drug repositories can reduce adverse events and inappropriate prescribing by enabling access to dispensed medication data at the point-of-care, but how they achieve this goal is largely unknown. OBJECTIVE To understand 1) the perceived clinical value; 2) the barriers and enablers to adoption; and 3) for which clinician groups a provincial, centralized drug repository may provide the most benefit. METHODS A mixed-method approach, including an online survey and semi-structured interviews, was employed. Participants were clinicians (e.g., nurses, physicians, and pharmacists) in Ontario who were eligible to use the Digital Health Drug Repository (DHDR), irrespective of actual use. Survey data were ranked on a 7-point adjectival scale and analyzed using descriptive statistics and interviews were analyzed using qualitative description. RESULTS : Of 167 survey respondents, only 24% (n=40) were actively using the DHDR. Perceptions of the utility of the DHDR were neutral (mean scores ranged from 4.11-4.76). Of the 76% who were not using the DHDR, 98% rated access to medication information (e.g., dose, strength, frequency) as important. Reasons for not using the DHDR included the cumbersome access process and the perception that available data was incomplete or inaccurate. A total of 33 interviews were completed, of which 26 were active DHDR users. The DHDR was a satisfactory source of secondary information, but the absence of medication instructions and prescribed medications (that were not dispensed) limited its ability to provide a comprehensive profile in order to meaningfully support clinical decision-making. CONCLUSIONS Digital drug repositories must adjust to align with clinician needs to provide value. Ensuring (1) integration with point-of-care systems; (2) comprehensive clinical data; and (3) streamlined onboarding processes would optimize clinically meaningful use. The electronic provision of accessible drug information to providers across healthcare settings has the potential to improve efficiency and reduce medication errors. CLINICALTRIAL N/A

Tailoring treatment of haemophilia B: accounting for the distribution and clearance of standard and extended half-life FIX concentrates

2017 ◽  
Vol 117 (06) ◽  
pp. 1023-1030 ◽  
Author(s):  
Alfonso Iorio ◽  
Kathelijn Fischer ◽  
Victor Blanchette ◽  
Savita Rangarajan ◽  
Guy Young ◽  
...  
Keyword(s):  
Half Life ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Individual Variability ◽  
Research Field ◽  
The Body ◽  
Factor Ix ◽  
Haemophilia B ◽  
Treatment Regimens ◽  
Sampling Times

SummaryThe prophylactic administration of factor IX (FIX) is considered the most effective treatment for haemophilia B. The inter-individual variability and complexity of the pharmacokinetics (PK) of FIX, and the rarity of the disease have hampered identification of an optimal treatment regimens. The recent introduction of extended half-life recombinant FIX molecules (EHL-rFIX), has prompted a thorough reassessment of the clinical efficacy, PK and pharmacodynamics of plasma-derived and recombinant FIX. First, using longer sampling times and multi-compartmental PK models has led to more precise (and favourable) PK for FIX than was appreciated in the past. Second, investigating the distribution of FIX in the body beyond the vascular space (which is implied by its complex kinetics) has opened a new research field on the role for extravascular FIX. Third, measuring plasma levels of EHL-rFIX has shown that different aPTT reagents have different accuracy in measuring different FIX molecules. How will this new knowledge reflect on clinical practice? Clinical decision making in haemophilia B requires some caution and expertise. First, comparisons between different FIX molecules must be assessed taking into consideration the comparability of the populations studied and the PK models used. Second, individual PK estimates must rely on multi-compartmental models, and would benefit from adopting a population PK approach. Optimal sampling times need to be adapted to the prolonged half-life of the new EHL FIX products. Finally, costs considerations may apply, which is beyond the scope of this manuscript but might be deeply connected with the PK considerations discussed in this communication.Supplementary Material to this article is available online at www.thrombosis-online.com.

scholarly journals Challenging, Accurate and Feasible: CAF-1 as a Tumour Proliferation Marker of Diagnostic and Prognostic Value

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2575
Author(s):  
Alexandros G. Sykaras ◽  
Alexandros Pergaris ◽  
Stamatios Theocharis
Keyword(s):  
Clinical Decision Making ◽  
Immunohistochemical Analysis ◽  
Clinical Decision ◽  
Attractive Alternative ◽  
Proliferation Marker ◽  
Clinical Value ◽  
Ki 67 ◽  
Proliferation Markers ◽  
Almost All ◽  
Tumour Proliferation

The discovery of novel biomarkers of diagnostic, prognostic, and therapeutic value is a major challenge of current cancer research. The assessment of tumour cell proliferative capacity is pivotal for grading and clinical decision-making, highlighting the importance of proliferation markers as diagnostic and prognostic tools. Currently, the immunohistochemical analysis of Ki-67 expression levels is routinely used in clinical settings to assess tumour proliferation. Inasmuch as the function of Ki-67 is not fully understood and its evaluation lacks standardization, there is interest in chromatin regulator proteins as alternative proliferation markers of clinical value. Here, we review recent evidence demonstrating that chromatin assembly factor 1 (CAF-1), a histone chaperone selectively expressed in cycling cells, is a proliferation marker of clinical value. CAF-1 expression, when evaluated by immunocytochemistry in breast cancer cytology smears and immunohistochemistry in cancer biopsies from several tissues, strongly correlates with the expression of Ki-67 and other proliferation markers. Notably, CAF-1 expression is upregulated in almost all cancers, and CAF-1 overexpression is significantly associated, in most cancer types, with high histological tumour grade, advanced stage, recurrence, metastasis, and decreased patient survival. These findings suggest that CAF-1 is a robust, reproducible, and feasible proliferation marker of prognostic importance. CAF-1 may represent an attractive alternative or complementary to Ki-67 for cancer stratification and clinical guidance.

Abstract TMP44: Personalizing Rehabilitation for Stroke Survivors- A Big Data Approach

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Swathi Kiran ◽  
Jason Godlove ◽  
Mahendra Advani ◽  
Veera Anantha
Keyword(s):  
Clinical Decision Making ◽  
Large Data ◽  
Clinical Decision ◽  
Individual Variability ◽  
Data Sets ◽  
Stroke Patients ◽  
Large Sets ◽  
Number Of Patients ◽  
Severity Scores ◽  
Evidenced Based

Introduction: Advances in connected health delivery provides a unique opportunity to maximize intervention effectiveness for stroke patients. It has also helped collect large sets of data to facilitate clinical decision making. This vastly insightful data is used to personalize neurorehabilitation where the evidence for gains in chronic stroke patients is weak. Methods: Over a span of 2 years (2013-2015), data was anonymously aggregated and analyzed from over 2,500 patients with post-stroke aphasia. Data was collected using a mobile therapy platform, Constant Therapy, which has 60 evidenced-based language and cognitive therapy tasks. The program was used by patients in the home and clinic under the guidance of a clinician, or under their own volition if not regularly seeing a clinician. This program dynamically adapted to each patient’s progress. Patients who completed between 3 and 1000 treatment sessions were analyzed to determine which tasks showed statistically significant changes. These data were compared with control patients who completed tests at two separate time points but with no intervening treatment. Results: Despite the older demographic of patients (median age = 64 yrs), they performed an average of over 20 minutes on home therapy every day. The analyses take into account the number of patients who completed a specific task and show a significant change (all p <.05) for accuracy or latency. For example, the 2-step Auditory Command task (which requires a user to follow 2-step directions) showed a 12 point gain in accuracy and 39% improvement in processing speed in 1,200 patients. The results also show that patients with higher initial severity scores showed significant gains in accuracy, and reach similar post-treatment accuracy to those with lower severity scores, provided that they received an appropriate dosage of therapy. In contrast, control patients showed minimal gains on tasks that were assigned. Conclusion: These results show that all patients, including the most severe, can make progress in their rehabilitation when treatment is individualized for them. Analysis of large data sets can be used to inform rehabilitation by highlighting therapies that are effective while accounting for etiology and individual variability.

2-18fluoro-deoxy-D-glucose Positron Emission Tomography Is a Reliable Predictor for Viable Tumor in Postchemotherapy Seminoma: An Update of the Prospective Multicentric SEMPET Trial

2004 ◽  
Vol 22 (6) ◽  
pp. 1034-1039 ◽  
Author(s):  
Maria De Santis ◽  
Alexander Becherer ◽  
Carsten Bokemeyer ◽  
Franz Stoiber ◽  
Karin Oechsle ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Predictive Value ◽  
Fdg Pet ◽  
Clinical Decision Making ◽  
Residual Tumor ◽  
Clinical Decision ◽  
Emission Tomography ◽  
Clinical Value ◽  
Positron Emission ◽  
Residual Lesions

Purpose To define the clinical value of 2-18fluoro-deoxy-D-glucose positron emission tomography (FDG PET) as a predictor for viable residual tumor in postchemotherapy seminoma residuals in a prospective multicentric trial. Patients and Methods FDG PET studies in patients with metastatic pure seminoma who had radiographically defined postchemotherapy residual masses were correlated with either the histology of the resected lesion or the clinical outcome documented by computer tomography (CT), tumor markers, and/or physical examination during follow-up. The size of the residual lesions on CT, either > 3 cm or ≤ 3 cm, was correlated with the presence or absence of viable residual tumor. Results Fifty-six FDG PET scans of 51 patients were assessable. All 19 cases with residual lesions > 3 cm and 35 (95%) of 37 with residual lesions ≤ 3 cm were correctly predicted by FDG PET. The specificity, sensitivity, positive predictive value, and negative predictive value of FDG PET were 100% (95% CI, 92% to 100%), 80% (95% CI, 44% to 95%), 100%, and 96%, respectively, versus 74% (95% CI, 58% to 85%), 70% (95% CI, 34% to 90%), 37%, and 92%, respectively, for CT discrimination of the residual tumor by size (> 3 cm/≤ 3 cm). Conclusion This investigation confirms that FDG PET is the best predictor of viable residual tumor in postchemotherapy seminoma residuals and should be used as a standard tool for clinical decision making in this patient group.

scholarly journals Impact of the Telephone Assistive Device (TAD) on stuttering severity while speaking on the telephone

2009 ◽  
Vol 56 (1) ◽  
Author(s):  
Nola Chambers
Keyword(s):  
Auditory Feedback ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Individual Variability ◽  
Assistive Device ◽  
Related Factors ◽  
Quasi Experimental ◽  
Repeated Use ◽  
Telephone Calls ◽  
Clinically Significant

There is extensive experimental evidence that altered auditory feedback (AAF) can have a clinically significant effect on the severity of speech symptoms in people who stutter. However, there is less evidence regarding whether these experimental effects can be observed in naturalistic everyday settings particularly when using the telephone. This study aimed to investigate the effectiveness of the Telephone Assistive Device® (TAD), which is designed to provide AAF on the telephone to people who stutter, on reducing stuttering severity. Nine adults participated in a quasi-experimental study. Stuttering severity was measured first without and then with the device in participants’ naturalistic settings while making and receiving telephone calls (immediate benefit). Participants were then allowed a week of repeated use of the device following which all measurements were repeated (delayed benefit). Overall, results revealed significant immediate benefits from the TAD in all call conditions. Delayed benefits in received and total calls were also significant. There was sub­stantial individual variability in response to the TAD but none of the demographic or speech-related factors measured in the study were found to significantly impact the benefit (immediate or delayed) derived from the TAD. Results have implications for clinical decision making for adults who stutter.

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